Arquivos Brasileiros de Cardiologia ou ABC Cardiol, acaba de atingir um patamar de reconhecimento internacional baseado no fator de impacto do ano 2020, que é um novo recorde na sua história.A publicação científica mais tradicional da Sociedade Brasileira de Cardiologia, com 73 anos de idade, ABC Cardiol é de 2,0, publicado pelo Journal of Citation Report  de 2020, o que significa que em média cada artigo publicado no ABC Cardiol teve 2 citações por outros artigos. Isto representa o impacto dos dados científicos publicados no ABC Cardiol na comunidade com produção científica ativa. Este índex vem subindo progressivamente nos últimos anos e o fator de impacto de 2 não é apenas um número isolado , which means that, on average, each article published in ABC Cardiol was cited 2 times by other articles. This represents the impact of scientific data published in ABC Cardiol in the actively productive scientific community. This index has been progressively rising over the past years, and the impact factor of 2 is not merely an isolated number (–ABC Cardiol holds first place among cardiovascular science journals in Latin America in international rankings, such as Scopus (d number .1–4 It is Scopus .ABC Cardiol has built in our scientific cardiology community in Brazil and worldwide. In fact, this result was achieved thanks to all the authors, reviewers, and editors who have continually supported the Brazilian Society of Cardiology's scientific journals. To all those who have supported us, I would like to say, “Thank you very much!”This achievement was made possible by the credibility that I would also like to thank the Brazilian Society of Cardiology, represented by the recent Presidents who have been the driving forces on this journey, Dr. Oscar Dutra, Dr. Marcelo Queiroga, and Dr. Celso Amodeo. Once again, “Thank you very much!”Also part of the Brazilian Society of Cardiology, our team of editorial assistants  is the tThe most important mission of this editorial is to say, “Thank you very much” to all those who are directly or indirectly involved in this wonderful result, which belongs to everyone who is part of our big cardiology community.ABC Cardiol in 2018 and 2019 were cited 548 times by other scientific articles. Many highly prestigious international journals have cited articles published in ABC Cardiol, including Circulation, Journal of the American Heart Association, Journal of the American College of Cardiology, Atherosclerosis, Journal of Clinical Hypertension, International Journal of Molecular Sciences, and many others. The cited articles include many original Brazilian and international articles. This year's impact factor relied less on citations of Brazilian Society of Cardiology Guidelines than that of previous years. Multiple Brazilian and international articles were cited a significant number of times in the international literature.To cite a few data related to this new impact factor, the 274 articles published in ABC Cardiol during the past 3 years all have long-standing traditions in Brazilian Cardiology, and they are displayed in The contributions of postgraduate programs and Brazilian universities have been fundamental to our impact factor, and, once more, I would like to say, “Thank you very much!” The Brazilian institutions that contributed the most papers to ABC Cardiol will make it possible to expand the scope of the Brazilian Society of Cardiology's scientific publications with the creation of a family of scientific journals.–ABC Heart Failure & Cardiomyopathy, which, in conjunction with the International Journal of Cardiovascular Sciences and ABC Cardiovascular Imaging, will compose the Brazilian Society of Cardiology's initial family of publications.Finally, the evolving quality of ABC Cardiol and the Brazilian Society of Cardiology's scientific journals have a bright and exciting future ahead of them. The Brazilian Society of Cardiology's scientific journals, on account of their credibility and responsibility,


We left out the appropriate permit information for collections done in Brazil. The following line should have been added to Acknowledgments (PDF page 16): “In Brazil, collections of biological samples and research on genetic resources were authorized by SISBIO permits 46555-1 to 46555-7 and CNPq permit 010936/2014-9.” This change does not affect the main text of the article in any way.Volume 11, no. 5, e02146-20, 2020,


Starch is one of the most common biodegradable polymers found in nature, and it is widely utilized in the food and beverage, bioplastic industry, paper industry, textile, and biofuel industries. Starch has received significant attention due to its environmental benignity, easy fabrication, relative abundance, non-toxicity, and biodegradability. However, native starch cannot be directly used due to its poor thermo-mechanical properties and higher water absorptivity. Therefore, native starch needs to be modified before its use. Major starch modification techniques include genetic, enzymatic, physical, and chemical. Among those, chemical modification techniques are widely employed in industries. This review presents comprehensive coverage of chemical starch modification techniques and genetic, enzymatic, and physical methods developed over the past few years. In addition, the current applications of chemically modified starch in the fields of packaging, adhesives, pharmaceuticals, agriculture, superabsorbent and wastewater treatment have also been discussed. Among those many different biopolymers, starch possesses intriguing characteristics such as its relative abundance, low cost, biodegradability, surface functionalization, renewability, and non-toxicity . Th3. The diameter of the granules generally ranges from 1 to 100 μm  that accelerate the production of highly functional derivatives . The enzAmong the four types of starch converting enzymes, debranching enzymes are widely employed in the industry. Besides the previously mentioned enzymes, lipase and protease are also used for starch modification . These eThe physical properties of the starch can be modified using physical processes. Physical processes are generally divided into thermal and non-thermal treatments . Table 3Usually, physically modified starch is considered natural as opposed to chemically modified starch . PhysicaOyeyinka et al.  studied 7 reduced down to 7.25 × 107, 5.42 × 107, 4.59 × 107, and 1.72 × 107 (Da) after 5, 10, 15, and 20 s of microwave treatment, respectively. Furthermore, Lewandowicz et al. [Xie et al.  exploredChemical modification involves the introduction of functional groups into the starch molecules. The chemical modification techniques depend on the starch source, reaction conditions such as concentration, reaction time, pH, the presence of a catalyst, and the type of substituent . ExampleCrosslinking of starch is the reaction between the hydroxyl groups of the starch molecule and a compound with two or more functional groups . A crossWidely used crosslinking agents are citric acid, glutaraldehyde, phosphorus oxychloride, sodium trimetaphosphate (STMP), sodium tripolyphosphate (STPP), and epichlorohydrin (EPI) ,60. CrosEpichlorohydrin (EPI), also known as 2-((chloromethyl)oxirane), is an organochlorine compound, see The blending of starch films with other synthetic or natural polymers is another common technique to improve the mechanical properties of starch. During mixing, EPI is used as a crosslinking agent. For example, potato starch-polyethene blended films, which were crosslinked with EPI, showed increased tensile strength and elongation at break of 54.48% and 8.32%, respectively . DetduanCanisag  compared2SO4) and hydrochloric acid (HCl) are commonly applied in acid hydrolysis. Acid hydrolysis is an electrophilic substitution reaction that occurred in the presence of an electrophilic hydroxonium ion (H3O+) supplied by the acid [3O+) supplied by the acid [3O+ molecules to the oxygen atom on the α-1,4-glycosidic bonds, as shown in Acid hydrolysis is one of the most widely used chemical processes. Acids including sulfuric acid  and sodium hydroxide (NaOH) are widely used to modify starch. However, the alkali medium works more effectively on dry starch. After the addition of alkali, the mixture should be neutralized using hydrochloric acid or acetic acid.Qin et al.  investigAccording to the research carried out by Sakkara et al. , the incEsterification is the substitution of hydrophilic hydroxyl groups of starch by various hydrophobic groups, as shown in d-glucose units is esterified with the acetyl groups, incorporating acetate functionality [In acetylation, the starch reacts with acetic anhydride to produce acetylated starch. The hydroxyl group of the ionality . Acetylaionality . The aceionality . The elaionality .Etherification of starch is usually achieved using epoxide reagents such as ethylene oxide. Initially, epoxides cleave the C-O bond under aqueous, acidic, or alcoholic conditions before the eventual condensation with starch, see Both esterification and etherification introduce lipophilic groups into the starch chains by reducing the hydrophilicity and the degree of inter-and intra-molecular hydrogen bonding . However2CO2H) in an alkaline solution while adding carboxymethyl groups at the -OH positions of starch by ether linkages. Upon the addition of carboxymethyl groups, the starch becomes more resistant to thermal degradation and bacterial attack [Carboxymethyl starch (CMS) is commonly used in the industry. The CMS is mainly produced due to its unique properties, such as high viscosity and stability . During l attack . In thisl attack , as showl attack  preparedIn oxidation, the hydroxyl groups at C-2, C-3, and C-6 are oxidized to carbonyl groups and then to carboxyl groups. After that, starch is hydrolyzed to amylose and amylopectin molecules by breaking α-1,4-glycosidic linkages, as shown in For instance, Fonseca et al.  preparedZavareze et al.  developeDuring grafting, synthetic or natural polymers are introduced to the backbone of the starch. The graft polymerization can tailor the chemical and physical properties of starch without changing the biodegradability . The majThe grafting reaction of starch is a free radical reaction and thus requires the treatment of initiators to yield free radical sites on the starch chain. After that, the starch chain acts as macro-initiators in the presence of synthetic monomers to obtain polymer grafts of high molecular weight . Li et aDual modification of starch involves combining either chemical and physical methods or chemical and enzymatic or genetic methods . Woggum The following section discusses the applications of enzymatically, physically, and chemically modified starch with the major focus on chemically modified starch.d-enzyme. Moreover, Montoya and coworkers reported starch acylation via the B-lipase of Candida antarctica [Enzymatically modified starch is commonly used in food and non-food applications such as pharmaceuticals and drug delivery systems . Enzymattarctica  and the tarctica  studied tarctica . Dura antarctica  obtainedPhysically modified starch is also utilized in food and non-food applications. Agama-Acevedo et al.  and Chi Apart from food applications, physically modified starch is extensively used in non-food applications such as packaging and 3D printing. For example, Bharti and coworkers  preparedChemically modified starch shows distinct properties over native starch and has been broadly explored in food packaging, pharmaceutical, water treatment, and agriculture applications ,114. TabChemically modified starch is mainly used in the food packaging industry due to its film-forming ability. For example, Peidayesh et al.  conducteHiremani et al.  preparedco-butyl acrylate). This study showed an increase in thermal stability. Furthermore, Chen et al. [Bio-based adhesives have gained much attention due to health and environmental concerns caused by petroleum-based adhesives. For example, Monroy et al.  and Chenn et al.  developeN, N′-methylene-bisacrylamide (MBA). This study demonstrated high relative hygroscopicity, water retention, and degradability of LSMM [Chemically modified starch has also been applied in pharmaceutical industries as biodegradable coatings and drug delivery systems. Hydrophilic and hydrophobic carboxymethyl starch derivatives were used to develop drug delivery systems, specifically micro-particles, nanoparticles, and hydrogels, by Lemos et al. . Quadrad of LSMM .Moreover, chemically modified starch also acts as a superabsorbent. Starch-based superabsorbents have been considered in personal care products, agriculture, forestry, chemical industry, and drug delivery systems. For instance, Czarnecka and Nowaczyk  preparedRecently, Soto and coworkers investigated the removal of cationic, methylene blue (MB), and anionic, methyl orange (MO) dyes present in water using succinylated starch. This study indicated that succinylated starch was superabsorbent material while being sensitive to changes in pH and the ionic strength of the medium. They also showed the removal of MB from an aqueous solution using succinylated starch .2+ ions in aqueous solutions. During starch modification, tetraethylorthosilicate (TEOS) was used as the chemical modifying agent, whereas Pluronic 123 was used as the structure-directing agent. The modified starch exhibited a maximum adsorption capacity of 330.3 mg/g while performing a higher desorption efficiency of over 97%.Gunawardene et al.  displaye2+ ions onto modified starch. This adsorption behavior can be well explained using Pearson’s hard-soft acid-base (HSAB) principle. According to 2+, resulting in interactions between the lead ions and hydroxyl groups in modified cassava starch [a starch . Table 52+ from aqueous solution using facile esterification reaction and graft copolymerization, respectively. Facile esterification reaction was used to prepare graphene-starch, and the results showed excellent adsorption towards Cd2+ ions at low concentrations from aqueous solutions [Apart from the above, Wang et al.  and Bai olutions . Furtherolutions  grafted Starch modification can be achieved by either genetic, enzymatic, physical, or chemical techniques. Although the enzymatic and genetic methods are not used in polymer industries due to the high production cost, they are considered mainly in the pharmaceutical and food industries. Physical methods are eco-friendly and low cost; however, they destroy starch structure limiting their industrial applications. Physically modified starch is used in food and non-food applications such as packaging and 3D printing. Chemical methods can alter the structural properties of starch to achieve the desired product attributes and are widely considered in the industry. Methods such as crosslinking, alkali treatment, etherification, esterification, acid hydrolyzing, grafting, and dual modifications can be used to prepare chemically modified starch and its derivatives. Chemical modification leads to changes in crystallinity, morphology, and molecular weight of starch while altering tensile strength, elongation at break, and adhesive properties of starch. Moreover, chemical modifications can also enhance the shelf-life and improve the quality, including excellent foaming, air, and moisture barrier properties. Chemically modified starch show potential in packaging, bio-based adhesives, pharmaceutical, agriculture, superabsorbent, and wastewater treatment applications. The major setbacks of modified starch include high water sensitivity, low mechanical properties, generation of toxic substances, and hard processability.The modified starch market is expected to grow in the food and beverages industry, as emulsifying agents and stabilizing agents owing to its gluten-free nature. In addition, the high demand for processed food, increased use of bio-based adhesives in various industrial applications, and the increased interest in the development of starch-based products will contribute to modified starch market growth. Moreover, the increasing demand for natural sweeteners in the food and beverages industry and the use of modified starch in the paper, cosmetics, and pharmaceuticals will increase the global modified starch market in the future.


The adequate transmittance of the resulting contact lenses was characterized by ultraviolet-visible spectrophotometry, and their satisfactory stability was examined using differential scanning calorimetry and thermogravimetric analysis. Whereafter, cytotoxicity and degradation experiments were performed to investigate the biocompatibility and degradability of the contact lenses. The results showed the nontoxicity and good degradability of the composites. Besides, the capacity of the contact lenses for in vitro release of EGCG was also evaluated, and the results showed that the EGCG in these contact lenses can be sustainably released for at least 14 days. Further bacterial adhesion assay suggested that the EGCG loaded starch hydrogel/contact lenses could significantly reduce the adhesion of Pseudomonas aeruginosa compared to the control. The EGCG loaded starch hydrogel/contact lens composites provide a potential intervention strategy for preventing ocular microbial infections and inhibiting bacterial keratitis.Microbial infections caused by wearing contact lenses has become a major health problem, so the design and development of antibacterial contact lenses has attracted widespread attention. To safely and effectively inhibit bacterial adhesion of contact lenses, we have facilely prepared epigallocatechin gallate (EGCG) loaded starch hydrogel/contact lens composites by  Pseudomonas aeruginosa (P. aeruginosa), an opportunistic Gram-negative pathogen, is the most common cause for the contact lens-associated bacterial keratitis . Methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) were obtained from ThermoFisher (United States). 2,2′-azobis (2-methylpropionitrile) (AIBN) was obtained from Sigma-Aldrich (United States) and deionized water was used in the study.2-Hydroxylethyl methacrylate (HEMA), Different amounts of starch solution , EGCG , HEMA/MAA , EGDMA (0.45 wt%), and AIBN (0.15 wt%) were mixed into the deionized water. The mixture was sonicated for 5 min, transferred into the contact lens molds, placed in a water-bath at 65°C for 30 h, and then boiled for 5 min to remove the unreacted monomers, affording contact lenses CL-0, CL-1, CL-2, CL-3. Conventional hydrogel contact lenses were prepared according to the same method mentioned above except the absence of starch  or both starch and EGCG (CL).The optical transmittances of the contact lenses were measured with an ultraviolet-visible spectrophotometer  at 50 nm intervals in the wavelength range of 250–800 nm. The contact lenses were removed from the molds, dried, and the dry weight (Wd) was recorded. Then immerse the contact lenses in deionized water to assess their expansion performance. Take out the lenses at regular intervals and drain the lenses surface completely with filter paper, and record their wet weight (Wt).Differential scanning calorimetry (DSC) detection and thermogravimetric analysis (TGA) were performed through the synchronous thermal analyzer . The experiment was performed in the following conditions: nitrogen purity, 99.999%; temperature, 20–600°C; sample weight, 5–10 mg. Fourier transform infrared spectrum analysis, X-ray photoelectron spectroscopy, and other characterization tests were carried out for the contact lenses with or without starch.The contact lenses were immersed into 4 ml of deionized water. At a predetermined time point, 1 ml of the release medium was taken out and replaced with an equal amount of fresh deionized water. NanoDrop One  was used to determine the content of EGCG at the wavelength of 278 nm. Then the cumulative release curve of EGCG with time was plotted by GraphPad Prism 9. The experiment was repeated three times.2 incubator for 24 h to obtain contact lenses extracts with concentrations of 1:4 and 1:2  was added to measure the absorbance of the cells at 450 nm wavelength with SpectraMax M2 .The cytotoxicity of EGCG loaded starch hydrogel/contact lens composites was evaluated based on the effects of contact lenses extracts on the proliferation of human corneal epithelial cells  through cell counting kit-8 (CCK-8) assay. 2.5 and 5 mg of different type contact lenses were respectively dipped in 10 ml DMEM/F12 (Sigma-Aldrich) containing 10% (v/v) fetal bovine serum (Sigma-Aldrich) and 1% (v/v) antibiotic/antimycotics (Sigma-Aldrich) in 37°C, 5% CO and 1:2 . While tin vitro degradation of starch in the EGCG loaded starch hydrogel/contact lens composites was evaluated by Bacillus alpha-amylase . Briefly, the contact lenses were immersed in iodine solution for 2 min, and the color of contact lenses was observed by slit lamp microscope. The contact lenses were rinsed gently with deionized water to remove residual iodine solution, and then soaked in active alpha-amylase solution for enzymatic hydrolysis at 50°C for 24 h . At estimated time points, the colorless lenses were taken out and softly rinsed with deionized water to remove residual amylase solution. After addition of iodine solution, the contact lenses were further photographed to detect the color reaction of starch and iodine.The P. aeruginosa ATCC 19660 inoculum was cultured on LB agar medium at 37°C, while planktonic culture was grown with an initial optical density (OD) of ∼0.02 and shaking in an incubator at 37°C for 24 h . All the data were obtained from at least three independent experiments. The descriptive statistics were presented as the mean ± SD. Microbial infection is a common problem associated with contact lenses, and poor sanitary conditions and overnight wearing contact lenses are the main risk factors for microbial keratitis . Long-teIn-situ free radical polymerization is a common method for preparation of therapeutic contact lenses by addition of bioactive ingredients. In this study, antibacterial contact lenses were facilely prepared by thermally initiated polymerization of the mixture containing starch, EGCG and conventional hydrogel components. Starch significantly improves the sustained release performance of conventional hydrogel contact lenses without changing the basic physical properties.The contact lenses were prepared according to specific ratio of different ingredients as reported previously . In shorThe addition of starch was confirmed through element analysis as shown in The optical transmittance data of contact lenses with different treatments are shown in Fourier transform infrared spectroscopy analysis showed that the corresponding functional groups of starch hydrogel contact lens did not change significantly. In addition, the characteristic peak of starch infrared absorption spectrum didn’t appear due to the low starch content . Figure in-situ synthesis, coating or covalently attachment. Although functional contact lenses containing antibiotics, non-steroidal anti-inflammatory drugs or silver ions have significant antibacterial properties, they could cause certain adverse reactions, such as the emergence of drug-resistant strains, eye irritation, and biocompatibility problems of metal ions  was stained with iodine solution and showed dark blue spots on the surface. After incubation with active alpha-amylase solution, the amounts of blue spots on the surface decreased with the increase of enzymatic hydrolysis time. The blue spots on the lenses disappeared after 12 h of enzymatic hydrolysis using the 0.1 mg/ml alpha-amylase solution, while there were still a few blue spots on the lenses after 24 h of enzymatic hydrolysis using the 0.01 mg/ml alpha-amylase solution  (p < 0.05). With the increase of EGCG content, the amount of bacterial adhesion on contact lenses decreased gradually   . Compare7 ± 751) . These rin-situ free radical polymerization of the mixture containing HEMA, MAA, EGDMA, starch and EGCG. The resulting composites exhibited favorable biocompatibility and superior drug release ability for EGCG at least 14 days, which processed enhanced sustained release capacity of EGCG than conventional hydrogel contact lens (4 days). Hence, they can effectively inhibit the adhesion of P. aeruginosa on the lenses, which is beneficial for prolonging the safe wearing of contact lenses and provides the potential for the clinical therapy of bacterial keratitis in the future. Furthermore, the study enriches the research scope of functional contact lenses, and various natural products with specific activities can be introduced in the preparation of therapeutic contact lenses for treatment of other ophthalmological diseases.In summary, the EGCG loaded starch hydrogel/contact lens composites have been successfully prepared by


The aim of this study was to evaluate the effect of cement on the fracture load of monolithic zirconia crowns with different yttria content (3 and 5 mol%).® Zirconia, Zirkonzahn) and 22 5Y-zirconia crowns  were produced to a shallow chamfer molar preparation. The 3Y-crowns were divided into four groups and attached to composite abutment duplicates  using the following four cementation techniques; (1) Self-adhesive resin-based cement, (2) Pre-treatment with air-abrasion and self-adhesive resin-based cement, (3) Zinc phosphate cement, (4) Glass-ionomer cement. The 5Y-crowns were divided into two groups and attached to the duplicates with; (1) Self-adhesive resin-based cement, or (2) Air-abrasion pre-treatment and self-adhesive resin-based cement. All crowns were loaded axially (0.5 mm/min) on the occlusal surface until fracture occurred.A total of 62 monolithic zirconia crowns, 40 3Y-zirconia crowns (Prettaup < .012). Among the 5Y-groups the air-abraded crowns fractured at statistically significant lower loads compared to the untreated crowns (p < .028). Load at fracture values were significantly different between the two zirconia materials (p < .001), with fracture loads ranging from 3873 to 7500 N in the 3Y-groups, and 2100 to 4948 N in the 5Y-groups.Among the 3Y-zirconia groups, the zinc phosphate cement group fractured at lower loads compared to the resin-based cement groups, with and without air-abrasion, (Resin-based cementation increased the fracture load compared to non-adhesive cementation. The 3Y-crowns fractured at almost twice the loads of the 5Y-crowns. Pre-treatment with air abrasion reduced the strength of the 5Y-crowns only, showing the importance of differentiating the treatment of the two materials. The development of yttria-stabilized tetragonal zirconia polycrystalline (Y-TZP) for dental purposes has resulted in a range of different products which can be used as a core material as well as a monolithic restoration without the use of veneering porcelain ,2. The mt] to monoclinic [m] phase when exposed to stress. The small volumetric increase following this transition causes compressive stress around the crack front, making it less likely to propagate ..20–22]. The fracture surfaces of all specimens were analyzed by light microscopy using fractographic methods to determine fracture origin and crack propagation. In cases where the fracture origin was difficult to determine, supplementary analyses were performed by scanning electron microscopy . At least two samples from each group were analyzed by SEM to verify the light microscopy findings. The inside of the crowns was used to examine the grain structure of the two different materials on two samples from each material group.U-test was used for between-group comparison. Spearman’s rank correlation coefficient was used to evaluate the association between margin quality and load at fracture. The level of significance was set to .05.Due to a tendency to skewed results non-parametric statistics were used to assess differences among groups with a statistical software package (STATA/SE 16.0). Kruskal–Wallis was used for overall comparison and Mann–Whitney p < .001). All crowns fractured during loading, with values ranging from 3873 to 7500 N in the 3Y zirconia crowns, and 2100 to 4948 N in the 5Y zirconia crowns . The group of crowns attached with zinc phosphate cement fractured at significantly lower loads compared to the resin-based cement groups, with and without air-abrasion, .Overall comparison of fracture load in the 3Y zirconia groups shows statistically significant differences among the four groups .In the 5Y zirconia crowns, there was a statistically significant difference between the air-abraded crowns, and the untreated crowns (Mann–Whitney n = 51) of the fractures originated in the mesial region, which also is the crown’s shortest wall  The 5Y crowns had generally more frayed margins than the 3Y zirconia crowns, and none of the 5Y crowns were without margin defects. Uneven margins ranged from grade 2 to 5, with a median of 3. The 3Y zirconia crowns had more even margins, where the majority of the crowns had few defects and were categorized as a grade 2.There was a statistically significant difference in the margin quality between the two material groups . More severe defects gave lower load at fracture. There was no correlation between margin quality and fracture load when the test was sorted by material.There was a statistically significant correlation between the severity of defects in the crown margins and the load at fracture  was chosen for the abutment replica, as it has been developed to simulate similar properties to dentine, although with somewhat lower elastic modulus . Human o in vivo ,41. All Within the limitations of this study, it has been shown that resin-based cement improves the fracture load of monolithic zirconia crowns. Pre-treatment with alumina air-abrasion resulted in lower loads at fracture for the 5Y zirconia crowns, while it did not affect the 3Y zirconia crowns.


The crowns were cemented to implant-supported zirconia abutments and the assembly fixed onto resin blocks. Fracture resistance was measured using a universal testing machine at a crosshead speed of 2 mm/min. A Kruskal–Wallis test was used to analyze the data. (3) Results: Although additively manufactured monolithic zirconia crowns demonstrated a higher mean fracture resistance than bi-layered alumina toughened zirconia crowns, statistical analysis revealed no significant difference in fracture resistance between the two groups. All specimens fractured at the implant–abutment interface. (4) Conclusions: Additively manufactured bi-layered alumina toughened zirconia crowns demonstrated similar fracture resistance to additively manufactured monolithic zirconia crowns when cemented to implant-supported zirconia abutments.(1) Background: This study compared the fracture resistance of additively manufactured monolithic zirconia and bi-layered alumina toughened zirconia crowns on implants. (2) Methods: Maxillary model with a dental implant replacing right second bicuspid was obtained. Custom abutments and full-contour crowns for additively manufactured monolithic zirconia and bi-layered alumina reinforced zirconia crowns ( Due to their optical properties, ceramics have long been used to mimic the appearance of natural teeth in dental restorations . Since tIncreasing demands for esthetic dentistry and tooth color restorations have led to utilizing ceramics in implant dentistry mostly for replacing missing teeth in the esthetic zone ,7. CeramInterestingly, contrasting the layered tooth structure, i.e., enamel and dentin, with other multilayer systems, such as porcelain fused to metal restorations or all ceramic restorations, reveals that a natural tooth has less chipping or cracking problem ,14. UniqMilling or subtractive manufacturing is the state-of-the-art technology to manufacture all-ceramic restorations, such as zirconia . HoweverAdditive manufacturing (AM) technologies also known as 3D printing are an alternative to milling for the fabrication of dental devices, mainly resin and metal prosthesis ,25,26 wiAdditive manufacturing enjoys several advantages over subtractive manufacturing, including fabrication of complex geometries and the ability to form structures in multiple materials. All the rapid prototyping techniques are based on similar premises. It has been demonstrated that by using different fabrication parameters, rapid prototyping can produce both fully sintered (solid) and partially sintered (more porous) structures. Accordingly, it is possible to utilize this process to create dental restorations with complex macro geometries and controlled gradient porosities, which cannot be fabricated using conventional machining technique. Therefore, AM potentially allows for the fabrication of functionally graded dental restorations emulating the mechanical properties of human enamel and dentin ,35,36,37The objective of the present in vitro study was to fabricate bi-layered all-ceramic dental crowns with zirconia and alumina toughened zirconia using additive manufacturing technologies and to compare the fracture resistance of bi-layered alumina toughened zirconia (AMAlZr) crowns with additively manufactured monolithic zirconia crowns (AMZr) when cemented to milled zirconia implant abutments. The null hypothesis would be that there are no significant differences in the fracture resistance of AM zirconia and AM bi-layered alumina toughened zirconia.1 file was used to manufacture zirconia implant abutments . A total of 20 zirconia abutments were milled.A maxillary model with an implant replacing right second bicuspid representing a clinical scenario was selected A,B. The 2 file  10 full-contour zirconia  crowns [2 file was split in thickness into 2 layers  crowns . Thereaf2 layers . The bot2 layers  and the 2 layers . A count2 layers .All the zirconia abutments were positioned on implant analog and torqued to 35 N/cm  Strauma.The screw access was sealed with a teflon tape and all the abutments and the intaglio surfaces of the crowns in both groups (AMZr and AMAlZr) were cleaned  following the manufacturer’s instruction. Subsequently, the crowns were cemented with a self-adhesive resin cement  on the abutments. The excess cement was cleaned using a 2 × 2 gauze, and all surfaces were cured with LED curing light  for 20 s to ensure adequate polymerization .A 12-mm deep hole was drilled into the center of cuboid polyurethane blocks  for mounting the implant analogs, abutment, and crown assemblies A,B usingA mandibular right second bicuspid Co-Cr crown was used as an antagonist to load the experimental crowns. It was cemented using resin cement  on a Titanium rod. The assembly contributed to the loading arm and was mounted onto the loading frame of the universal testing machine  .Polyurethane blocks harboring the abutment and crown assemblies were affixed between two metal arms on the horizontal platform of the universal testing machine . The specimens and the loading metal crown were positioned into maximum intercuspation. All specimens were subjected to static vertical loading using the universal testing machine  at a crosshead speed of 2 mm/min and 25 kN load cell ,39. ForcA statistical software  was used to calculate the means and standard deviations of the fracture resistance in both groups. The Mann Whitney U test was used to determine the existence of a significant difference, if any, in fracture resistance between the groups as the data were not normally distributed.p = 0.6) between the two groups.Although the AMZr crowns demonstrated a higher median fracture resistance (1243.5 ± 265.5 N) than AMAlZr (1209 ± 204.5 N) crowns , the ManSamples in both groups fractured at the abutment level near the interface of zirconia abutment and implant analog with no significant differences between two groups . The croThe bi-layered ceramic restorations were expected to demonstrate higher values for fracture resistance, owing to their tendency to mimic the structure of human enamel and dentin. The goal of this study was to evaluate the potential of additive manufacturing in fabricating a bi-layered design as a first step to create a multilayered graded structural design which represents human enamel and dentin ,34,35,36The concept of a bioinspired graded structure relies upon designing a restoration, such that it mimics the architecture of enamel and dentin in natural tooth. In that context, it means that the reduction in hardness and modulus of elasticity in a dental crown should reflect a continuous gradient from occlusal to the intaglio surface ,37. AlthZirconia abutments were used in this in vitro study instead of metal abutments, because of their superior esthetic for patients with a high lip line and thin gingival phenotype ,9,10. AlAlthough AM offers many advantages, the AM of dental ceramics is not a valid and accepted fabrication technique yet. There have been very limited studies on 3D printing of dental ceramics with no published studies that have investigated the fracture resistance of 3D printed bi-layered alumina reinforced zirconia ceramic crowns supported by implants ,44 to coZirconia abutments were the common mode of failure for all the specimens after mechanical loading and the result is similar to a previous study by Martinez et al.  Using tiFracture of the veneering material, including porcelain chipping is the most common complication associated with implant-supported prostheses. This percentage was higher with all-ceramic crowns . CollectBased on the experimental design and the limitations of the present study, no significant differences were encountered in fracture resistance between additively manufactured monolithic zirconia and bi-layered alumina toughened zirconia crowns. Based on the results obtained, AM appears to be a promising technology for fabricating zirconia and alumina toughened zirconia restorations with great potential for improvement in the near future. The expansion of the AM technology can incorporate the fabrication of ceramic based bio-inspired graded structural crowns as a treatment modality and allow for the exploration of their physical and mechanical properties.


Almost a hundred years has passed since neurosurgery became an official surgical specialty of medicine. Forged from the field of general surgery, the founders of modern neurosurgery were able to progress the field despite having rudimentary methods of anesthesia, electrocautery, understanding of post-operative hematomas, and ways to monitor intracranial pressure.Journal of Neurosurgery was created in 1944 by the American Association of Neurological Surgeons receiving submissions from all over the world [The combination of increased understanding of antiseptic techniques, advancements in surgical technologies, and early experimental successes lead to the formation of the first organized group called the Society of Neurological Surgeons in the United States in 1919. Later leading to the formation of other American societies and groups, such as The Harvey Cushing Society in 1932 [Today there are nearly two hundred neurosurgery related journals around the world and more than ten neurosurgery related journals in China . AlthougChinese Neurosurgical Journal aims to publish work in all areas of neurosurgery from neurosurgeons and neurosurgical researchers not only from China, but also from physicians and scientists from all over the world. The journal also focuses on clinical practice and techniques, including clinical and basic science research studies, book reviews, case reports, commentaries, letters to the editor, and reviews. We believe this journal will serve the global scientific community as an excellent vessel to exchange information between Chinese neurosurgeons and neurosurgeons from other countries. We also expect that this new English version of the Chinese Neurosurgical Journal will enjoy success under the leadership of Professor Jizhong Zhao, and will greatly contribute to neurosurgical research worldwide.Professor Jizong Zhao, the first Editor-in-Chief, is to be commended for forward thinking and assisting in the courageous decision to provide a true international journal. The


Portal vein shunt is common in chronic hepatic diseases and after a liver transplant. Ensuring a satisfactory portal flow is essential to support a rapid liver recovery, of paramount importance to meet the recipient’s metabolic needs.We report the case of a 32-year-old female undergoing a third liver transplant due to recurrence of graft failure secondary to portosystemic shunting. The patient, affected with biliary atresia, was first transplanted in 2009 with a right split liver graft. The clinical course was complicated by biliary stenosis of the Roux-en-Y anastomosis and multiple episodes of acute rejection treated with steroid boluses, plastic dilation of the biliary anastomosis, and biliary catheter placement. Unfortunately, in 2017 a liver biopsy showed an autoimmunity with histological evidence of ANA 1:80 (granular and nucleolar pattern). This was a contributing factor of liver function impairment, leading to the need to perform a second liver transplant, complicated by an acute rejection, with only a partial response to steroid therapy. Due to the further worsening of the liver function , the patient was relisted for a liver transplant. After five days, she received her third liver transplant, with an entire graft of an AB0 identical group. Intraoperative exploration revealed multiple collaterals and large splenocaval shunts, with a significant alteration of the portal flow and hypertension, isolated and closed with a vascular stapler to restore the graft's regular portal vein flow.In patients listed for a liver transplant, portal steal syndrome should be identified prior to the transplant. Our recommendation is to consider intraoperative or perioperative closure of the portal collateral varices. Orthotopic liver transplantation (OLTx) is frequently followed by vascular complications with a high incidence of graft loss and mortality.Portal vein thrombosis (PVT) with complete or partial obstruction of the portal vein flow (PVF) is a known development of acute or advanced chronic liver disease and a major risk during operative and perioperative time .Diagnosis and early treatment of vascular thrombosis in cirrhotic patients can improve the success rate of liver transplantation. This makes it absolutely necessary to perform regular ultrasound follow-up to evaluate the portal flow and establish a surgical program during the transplant, such as portal obstruction or vascular reconstruction with a portal by-pass.Literature reports a PVT incidence at the time of transplant evaluation of 26% in patients requiring an OLTx [Portal vein shunt is common in chronic hepatic disease and after a liver transplant. Ensuring a satisfactory portal flow is mandatory to support a rapid liver recovery, which is paramount to meet the recipient’s metabolic needs .Portal hypertensive liver cirrhosis leads to a progressively-increased resistance of the hepatic sinusoids, which in turn prompts the shunting of portal flow in the systemic circulation via less resistive collateral vessels –7.We report the case of a 32-year-old female at her third liver transplant due to recurrence of graft failure secondary to portosystemic shunting.The patient, affected with biliary atresia, was first transplanted in 2009 with a right split liver graft. Clinical course was complicated by biliary stenosis of the Roux-en-Y anastomosis and multiple episodes of acute rejection treated with steroid boluses, plastic dilation of the biliary anastomosis, and biliary catheter placement. Unfortunately, in 2017 a liver biopsy showed an autoimmunity with histological evidence of antinuclear antibodies (ANA) 1:80 (granular and nucleolar pattern). This was a contributing factor of liver function impairment, requiring a second liver transplant.Due to the complete portal vein thrombosis, during the operation a venous conduit was performed with an interposition graft of cadaveric iliac vein, anastomosed between the native spleno-mesenteric vein confluence and the main portal vein of the graft.This procedure had a good clinical outcome, with a complete recovery three weeks after surgery. Computed tomography (CT) scan was performed with intravenous contrast and vascular reconstruction: multiplanar reconstruction (MPR), maximum intensity projection (MIP), and volume rendering (VR) showed a perfect patency of the venous conduit Fig. a.Fig. 1CAfter one year, the woman became pregnant and delivered a healthy girl. In 2021, there was a new onset of jaundice and acute liver rejection. The patient underwent radiological assessment with CT scan to exclude portal vein thrombosis and related vascular occlusion. There was a tomographic finding of patent venous conduit and hypertrophy of the azygos and hemiazygos systems, and large retroperitoneal varices with wide outflow in the subrenal vena cava  of 8/9, treated with steroid bolus with partial response. Due to the further worsening of the liver function (Model for End-Stage Liver Disease (MELD): 40, Child–Pugh: C11), the patient was relisted for a liver transplant. After five days, she received a third liver transplant, with an entire graft of an AB0 identical group.A Doppler US confirmed an inadequate portal inflow of the graft, and the need to suture the wide varices to restore the portal inflow.Intraoperative exploration revealed multiple collaterals and large splenocaval shunts, with a significant alteration of the portal flow and hypertension, isolated and closed with a vascular stapler to restore the graft's regular portal vein flow.The recipient’s portal vein was anastomosed in an end-to-end fashion between the old venous conduit and the graft portal vein.The stapler transection was immediately followed by an improvement of the portal vein flow, evidenced on Doppler (81.4 cm/s). Conventional arterial reconstruction was performed between the recipient's arterial and the graft's hepatic artery. Wider Roux-en-Y biliary reconstruction was performed.A routine Doppler US after the transplant confirmed an adequate portal blood flow Fig. , and theA portosystemic shunt (PSS) is an abnormal vascular connection between the portal vein branches and the systemic circulation in the liver. The natural history of a PSS is strongly dependant on its gauge. The shunt will tend to progressively increase, often causing an inversion of the flow and the related clinical symptoms. Portal flow variations can cause occlusion or PVT, one of the most feared complications during a transplant.The aim of this report is also to highlight the importance of a preoperative study of transplant candidates with a personalized surgical program for patients with PVT. These patients require an accurate Doppler US to highlight potential alterations in the normal vein waveform, which must always be investigated with a CT scan to evaluate the portal vein integrity or the presence of thrombosis.Progressive PSS can determine graft failure through a stealing of portal flow due to changes in portal venous anatomical system and in the hemodynamics. Patients affected by PSS always develop systemic syndromes, such as ascites and hepatorenal syndrome, which can cause a worsening of the renal function leading to renal insufficiency with considerable sodium retention. Progressive peripheral vasodilation increases the glomerular filtration rate determining a renal accumulation of angiotensin II. The increased tubular sodium reabsorption generates an ascitic decompensation that initially appears responsive to depletion diuretic treatment, but that often has a degenerative trend developing refractory ascites that requires paracentesis.At this regard, a portosystemic shunt must be closed to avoid inadequate portal inflow to the graft, leading to graft loss. Increased hepatic vascular resistance due to acute rejection, fluids overload, or a small-for-size graft can hinder spontaneous regression of the shunt.site and size of varices;diameter and patency of the main portal vein in order to establish a clinical strategy.Accurate tomographic vascular reconstruction is necessary –10 to asAt present, there are no shared guidelines for the management of portosystemic shunt, before or after liver transplantation, and evidence of effective treatments is indeed limited.After a multidisciplinary evaluation and review of the clinical reports, we identified the occurrence of portal vein shunt as the cause of progressive graft impairment in our patient.In the case reviewed, we found strong evidence of the importance of portosystemic steal in causing chronic liver damage without thrombosis of the main portal vein , 12.In our tomographic reconstruction, before the third transplant, we were able to appreciate a normal portal vein, with no signs of thrombosis and ultra-sonographic evidence of hepatofugal flow.In patients listed for a liver transplant, portal steal syndrome should be identified prior to transplant, and we also recommend to consider intraoperative or perioperative closure of the portal collateral varices.


To determine the benefit of performing transperineal prostate mapping biopsy (TPMB) following multiparametric magnetic resonance imaging (mpMRI) to increase the identification of clinically significant prostate cancer (csPCa) with Gleason grade group (GG) ≥ 2 and their locations outside of the PI‐RADS v2 3–5 category lesions.mpMRI was performed in 80 men prior TPMB from two institutions. The mpMRI was considered clinically significant (csMRI) if it contained one or more PI‐RADS 3–5 category lesion. mpMRI findings were compared against csPCa diagnosed by TPMB, performed between 16 November 2010, and 13 September 2019, for the entire gland, both lobes and to the right and left anterior and right and left posterior quadrants . Sensitivity, specificity, positive and negative predictive values , accuracy and the area under curve (AUC) were determined. Thirteen men also underwent radical prostatectomy and had comparison of TPMB pathology to prostatectomy specimen grading.TPMB was positive in 60/80 (75%) of which 32 (53.3%) were csPCa. csPCa was present in the RA in 9 (11.3%), LA in 11 (13.8%), RP in 25 (31.3%) and LP in 27 (33.8%) and involved 1 quadrant in 7 (21.9%), 2 quadrants in 12 (37.5%), 3 quadrants in 11 (34.4%) and all 4 quadrants in 2 (6.3%) patients; 57/80 (71.3%) men had a mpMRIs with lesions designated as PI‐RADS 3 in 24 (30%), 4 in 25 (31.3%) and 5 in 8 (10%). A csMRI was present in the RA in 7 (8.8%), LA in 8 (10%), RP in 31 (38.8%) and in the LP in 29 (36.3%), which were limited to one quadrant in 39 (68.4%), 2 quadrants in 16 (28.1%), and 3 quadrants in 2 (3.5%). Sensitivity, specificity, PPV, and NPV were determined from the results of the TPMB and were for the entire gland 81.3%, 35.4%, 45.6% and 73.9%. There were 31 csMRIs involving the right posterior of the gland but only 25 csPCa by TPMB of which 12/31 (38.7%) were concordant for high grade disease. There were 29 men who have a csMRI in the left posterior quadrant, and 14 (48.3%) were concordant with csPCa from the TPMB.MpMRI should be supplemented with TPMB to correctly identify the regions of the prostate that would require ablation in men considering focal therapy. An mpMRI study utilising the Prostate Imaging and Data Reporting System version 2 (PI‐RADS v2) criteria accurately identifies high grade PCa when a score of 5 is present.Physicians are increasingly interested in focal therapy, and more than 50% of urologists in a recent survey believed focal therapy is beneficial in the treatment of PCa, but 63.2% were also concerned that only treating the index lesion would be inadequate.TPMB has been shown to identify more csPCa than TRUS biopsy including the small lesions missed by mpMRI.2n = 65) and Hygeia Brachytherapy Center  had an mpMRI prior to TPMB between 16 November 2010, and 13 September 2019. Eleven (13.8%) men were biopsy naïve, 18 (22.5%) were biopsy negative and 51 (63.7%) had a prior positive TRUS biopsy of which 37 (75.2%) had Gleason grade group (GG) 1, 12 (28.5%) had GG 2, 1 had GG 3 and 1 GG 5. The mpMRI and TPMB were compared to determine the presence, grade and location of the cancer and if the patient was a candidate for focal therapy. Subtotal treatment of the gland could be considered for clinically significant prostate cancer (csPCa), defined as GG ≥ 2, and occupying 3 (out of 4) or less quadrants.Eighty patients from the University of Colorado Hospital  and dynamic contrast. At HBC, mpMRIs were performed on 3.0 Tesla scanners with endorectal coils with contrast utilising the same sequences. The MR‐T2 images were loaded into proprietary software and ROIs were segmented  under anaesthesia using an 18‐G disposable biopsy device through a 5‐mm template as previously described.Thirteen men had radical prostatectomy surgery, and the final histopathology was compared with the mapping results to determine grading concordance between the two. Associations between GG and the number of positive biopsy sites were determined by analysis of variance (ANOVA) (bootstrapping). Contingency tables (Pearson chi‐square) were constructed for csPCa (derived from the TPMB) versus csMRI. Sensitivity, specificity, positive predictive value (PPV), NPV, accuracy and the area under the curve (AUC) were calculated for the entire prostate, both sides of the gland and for the four sectors. A csMRI confirmed by a csPCa from the TPMB was considered a true positive. The highest GG from the TPMB was compared with the highest GG from the prostatectomy specimen to determine grading accuracy. An increase by a GG of 1 or more was considered upgrading. Two‐way analyses with a significance ≤ 0.05 were performed using SPSS v.20. All data were de‐identified and anonymised and approved for reporting by the institutional review boards.3p = 0.002). csPCa was present in the RA in 9 (11.3%), LA in 11 (13.8%), RP in 25 (31.3%) and LP in 27 (33.8%). By quadrant, csPCa was localised to 1 quadrant only in 7 (21.9%), 2 quadrants in 12 (37.5%), 3 quadrants in 11 (34.4%) and in all 4 quadrants in 2 (6.3%); 30/32 (93.8%) men had csPCa isolated to 3 or fewer quadrants; 9/32 (28.1%) men had csPCa limited to one side of the prostate. The mean (range) number of cores containing csPCa by quadrant location were RA 9.2,The median (range) patient age, prostate‐specific antigen (PSA) and prostate‐specific antigen density (PSAD) were 64.0 (46–82) years and 6.0 ng/mL 1–32) and 0.13 (0.019–1.1) (Table –32 and 0Fifty‐seven of 80 71.3%) men had csMRI with PI‐RADS lesions designated as 3 in 24 (30%), 4 in 25 (31.3%) and 5 in 8 (10%). A csMRI was present in the RA in 7 (8.8%), LA in 8 (10%), RP in 31 (38.8%) and in the LP in 29 (36.3%) and limited to one quadrant in 39 (68.4%), 2 quadrants in 16 (28.1%) and 3 quadrants in 2 (3.5%). Forty‐one (71.9%) had a csMRI limited to one side of the prostate. Of the 31 csMRIs involving the right posterior of the gland and 29 in the left posterior quadrant, only 12 (38.7%) on the right and 14 (48.3%) on the left were concordant with the TPMB for csPCa  when compared with the mapping biopsy results. No cases were upgraded, whereas there was a downgrade of 1 GG in 3 patients. These three cases remained clinically significant despite the downgrade; 58/60 men with PCa underwent treatment or active surveillance Table ; 10/13 w4This investigation determined that a TPMB following mpMRI provides regions (quadrants) of the prostate containing csPCa missed by PI‐RADS 3–5 criteria with consequent improvement in the patient selection for focal therapy. The ‘classic’ hemi‐ablation or ‘hockey‐stick’ ablation pattern often recommended for focal ablation may not be ideal based on the results of this study. The quadrants most involved with csPCa are the two posterior zones, which made up 31.3% of the potential cases. A unilateral ablation could be considered in nine men, while just the right or left posterior quadrants in seven Table . Only twSeveral investigators have documented the limitations of mpMRI in identifying smaller PCa lesions. Johnson et al. reported when mpMRI was compared with WMRP specimens, only 45% of all PCa lesions and 65% of csPCa were detected.p < 0.001).p = 0.02).Systematic and targeted biopsy performed by the transperineal route can improve identification of csPCa. Radtke et al. reviewed 755 men who had transperineal fusion biopsy of mpMRI‐suspicious lesions followed by transperineal saturation biopsy .n = 13), no patients were upgraded, and only one downgraded without a change in csPCa status.The benchmark for validating the accuracy of a PCa detection protocol is the prostatectomy specimen. Alshak et al. performed fusion biopsy on 140 men and found 9/17 (52.9%) of the biopsies were upgraded from GG 1 to 2 compared to the prostatectomy specimens while 10/60 (16.7%) were downgraded from GG 2 to 1.Physicians pursuing focal therapy have utilised brachytherapy, HIFU, laser, electroporation, cryotherapy and radio frequency to create ablation zones.The major limitation of this study was the relatively small sample size. However, the thorough interrogation of the prostate using a TPMB with a high biopsy density highlighted the benefit of incorporating this strategy after mpMRI to identify the regions of the prostate containing csPC. This study did not compare the TPMB to mpMRI plus 12‐core systematic biopsy. Although the latter does improve the detection of csPCa away from a PI‐RADS 3–5 ROI, it does not provide the precise localisation information generated from a thorough transperineal mapping procedure. There may also be a benefit to using a quadrant approach as opposed to lesions with a margin when considering partial gland ablation. This investigation did not address the costs associated with TRUS biopsy, TPMB and mpMRI. An outpatient TRUS is less costly than a TPMB, which has typically been performed in the operating room under anaesthesia, although new devices have been introduced allowing a TPMB to be done in the office with local anaesthesia.Of the 80 men who had a TPMB biopsy, 20 (25%) were negative. In contrast to an office TRUS biopsy where 30% of negative biopsies are false negatives (for csPCa) and need to be repeated, the likelihood of a false negative TPMB should be very low. Unless there is an increase in PSA or other clinical determinate, most of these men will not require a repeat biopsy.This investigation did not directly compare TPMB with fusion biopsy. mpMRI‐based fusion biopsy with 12‐core systematic biopsy should be compared to a more extensive mapping in a randomised study. An investigation of this type could ascertain if there is a benefit to take biopsies for improved diagnosis of csPCa and to improve cancer localization for partial gland ablation. Validation of the latter could be accomplished by comparison with the radical prostatectomy specimens.5Transperineal mapping biopsy can enhance an mpMRI when considering partial gland ablation. It can aid in the selection of men for active surveillance by accurately excluding men with high grade disease. All the men who elected active surveillance in this investigation had Gleason GG 1 confirmed by TPMB. TPMB also accurately identified csPCa not detected by the MRI allowing the physician to correctly select the quadrants of the prostate that require ablation. This approach can increase the percent of men who are diagnosed with PCa for consideration of subtotal gland treatment. The most common portion of the prostate that qualifies for hemi‐ablation is both posterior zones.N. N. Stone and M. S. Lucia have ownerships in Triopsy, Inc. There was no financial assistance from Triopsy in this investigation or in the production of the manuscript.All authors contributed to the data collection, production of the manuscript and submission review.


Sixteen dietary treatments were formulated with 4 levels of sugar , and 4 levels of starch . Samples were taken at 0.5, 1, 3, 6, 12, and 24 h after cultivation to determine the disappearance rate of dry matter, rumen fermentation parameters and bacterial community composition. Butyric acid, gas production, and Treponema abundance were significantly influenced by the sugar level. The pH, acetic acid, and propionic acid levels were significantly influenced by starch levels. However, the interactive effect of sugar and starch was only observed on the rate of dry matter disappearance. Furthermore, different combinations of starch and sugar had different effects on volatile fatty acid production rate, gas production rate, and dry matter disappearance rate. The production rate of rumen fermentation parameters in the high sugar group was higher. Additionally, increasing the sugar content in the diet did not change the main phylum composition in the rumen, but significantly increased the relative abundance of Bacteroidetes and Firmicutes phyla, while the relative abundance of Proteobacteria was reduced. At the genus level, the high glucose group showed significantly higher relative abundance of Treponema (P < 0.05) and significantly lower relative abundance of Ruminobacter, Ruminococcus, and Streptococcus (P < 0.05). In conclusion, different combinations of sugar and starch concentrations have inconsistent effects on rumen fermentation characteristics, suggesting that the starch in diets cannot be simply replaced with sugar; the combined effects of sugar and starch should be considered to improve the feed utilization rate.High levels of starch is known to have positive effects on both energy supply and milk yield but increases the risk of rumen acidosis. The use of sugar as a non-structural carbohydrate could circumvent this risk while maintaining the benefits, but its effects and that of the simultaneous use of both sugar and starch are not as well-understood. This study aimed to evaluate the effects of different combinations of sugar and starch concentrations on ruminal fermentation and bacterial community composition  Starch and sugar are non-structural carbohydrates (NSCs), and are the main energy source for ruminants. Starch is the primary source of NSC in the diets of lactating dairy cows . High coin vitro, and examined whether the different combinations can change bacterial community composition.There are few studies on the effect of the combination of sugar and starch, and their interaction in diets. Therefore, the aim of the present study was to assess the effect of different combinations of sugar and starch on ruminal fermentation Ruminal fluid for this experiment was obtained from three male small-tailed Han sheep  fitted with a ruminal fistula. Animals were kept in individual rearing cages and were given free access to clean water. All experimental procedures were according to the Guidelines for the Care and Use of Experimental Animals of Jilin Agricultural University.in vitro using a 4 ×4 full factorial experimental design comprising a total of 16 groups of rations , the bottle cap was covered immediately, and the bottles were returned to the laboratory quickly. A 5 L beaker was preheated in a 39°C water bath, and the collected rumen fluid was filtered into the beaker through four layers of cheesecloth. CO2 was passed to ensure an anaerobic environment, and the rumen fluid filtrates of the three sheep were mixed well to obtain the rumen inoculum. In vitro digestibility of samples was measured using the Ankom DaisyII Incubator system . The weight of each F58 filter bag was measured  and recorded as W1. Then, 1 g of the sample (W2) was weighed and placed directly into the filter bag. The bags were sealed using heat  and were placed in the DaisyII Incubator digestion jar. Three sealed blank bags were included in each digestion jar for correction factor (C1). The incubation jars were pre-heated to 39°C before beginning the experiment. The buffer was prepared anaerobically as described by Menke and Steingass  was determined based on the following equation.Before feeding in the morning, a polyvinyl chloride tube was used to collect rumen fluid from different points in the rumen of the sheep teingass , and eacW1 = Bag tare weight;Where, W2 = Sample weight;W3 = Final bag weight after in vitro experiment;C1 = Blank bag correction .in vitro experiment. Two grams of the different diets  was used for the 3-N). Additionally, 1 mL of sample was collected and mixed with 200 μL of metaphosphoric acid and stored in a −20°C refrigerator for determining VFAs. The remaining sample was preserved at −80°C for bacterial-community composition analyses.The fermenters were taken out at 0.5, 1, 3, 6, 12, and 24 h post incubation and the bottle cap was opened instantly. The fermenters were then placed in cold water to stop the fermentation. Next, 5 mL of the samples was collected and stored in a −20°C refrigerator for measuring ammonia nitrogen  was used to determine the ruminal pH, and a Shimadzu UV-1201 spectrophotometer  was used to measure the NH Marbach . VFAs weR2) was >0.95, the Gompertz model equation fitting degree (R2) was >0.90 , and the Logistic model equation fitting degree (R2) was >0.83 .Origin (version 2018) software was used to fit sigmoidal curve. The logarithmic model equation fitting degree  followed by removing of chimera (via uchime_denovo). Finally, the non-chimera sequences were re-clustered at 97% to generate OTU representative sequences and OTU table. The Greengenes database and QIIME2 classify-sklearn algorithm were used: For the representative sequence of each OTU, use the pre-trained Naive Bayes classifier to enter the species annotation. PICRUSt analysis was used to predict functional profiles of rumen bacterial communities. Then according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, predicted genes were summarized. The alpha-diversity metrics , observo1, Chao  indices Yijk = μ+ Fi + Vj + Fi×Vj + eijk, where μ is the overall mean, Fi is the effect of starch (i = 1–4), Vj is the effect of sugar (j = 1–4), Fi × Vj is starch × sugar level interaction, and eijk is the residual effect. Duncan contrasts were used to test the significance level for the effects of starch, sugar, and their interactions (starch × sugar), with P < 0.05 defined as statistical significance. The rumen fermentation parameters values were subjected to model curve fitting using origin 2018 software. At the same time, each parameter value in these model equations was calculated and the theoretical maximum yield, theoretical inflection point (maximum generation rate), and time for theoretical inflection point were calculated.All groups were analyzed for DM digestibility and rumen fermentation parameters. The four groups st1su1 (Hl: 270 g/kg + 60 g/kg), st1su2 (Hh: 270 g/kg + 120 g/kg), st4su1 (Ll: 210 g/kg + 60 g/kg), and st4su4 (Lh: 210 g/kg + 120 g/kg) were further analyzed for the abundance of bacterial communities after fermentation for 24 h. All data were analyzed by two-way analysis of variance (ANOVA) using the General Linear Model Repeated Measure of SPSS software version 22.0. Data were analyzed using the model: P < 0.01) and the interaction of starch and sugar (P < 0.01). pH was significantly affected by starch (P < 0.01). Gas production was significantly affected by starch in the later period of culture and by sugar after 3–24 h of cultivation. Acetic acid was significantly affected by starch after 1–3 h and 12–24 h in vitro and by the interaction between starch and sugar. Propionic acid was significantly affected by starch at 1–6 and 24 h in vitro, and was significantly affected by sugar at 6 h in vitro. Both butyric acid and total volatile fatty acid (TVFA) contents were significantly affected by sugar after 1–24 h in vitro. TVFA was significantly affected by starch in the early stage of culture (0.5–6 h). The ratio of acetic to propionic acid (A/P ratio) was significantly affected by starch after 6 h and by sugar after 6–12 h.The effects of starch and sugar on rumen fermentation parameters are presented in R2 > 0.83; 8. Specifically, the accumulation amounts of fermentation index differed between groups at 24 h. Moreover, the maximum production rate and its production time also differed among groups with similar accumulation amounts. When the starch concentration in the diet was 25%, the accumulation of acetic acid among the groups with different sugar content was similar, but the maximum production rate differed by 3–4-fold. Increasing the sugar concentration in the diet could increase the production rate of fermentation products and advance the time of maximum production rate.These results indicated that these three equations have high fitting degrees (P < 0.05).unidentified_ Bacteroidales (20.57%), Prevotella (20.17%), Ruminobacter (10.54%), CF231 (8.15%), and Ruminococcus (3.12%) being the most abundant , with Bacteroidetes (50.02%), Firmicutes (18.86), Proteobacteria (12.92%), Tenericutes (2.30%), and Verrucomicrobia (2.18%) being the most abundant. The predominant bacterial taxa at the genus level (with relative abundance being > 0.10% in each sample) consisted of 34 genera, with abundant .Ruminococcus and Pseudobutyrivibrio was affected by starch (P < 0.05), with Ruminococcus being the prominent genus in the H starch groups. Sugar had effects on the relative abundance of BF311, unidentified_Bacteroidales, Streptococcus, unclassified_Clostridiales, Ruminobacter, and Acinetobacter (P < 0.05). Furthermore, unidentified_Bacteroidales1, Oscillospira, and BF31 were distinguished as prominent genera in H sugar groups, while the relative abundance of Ruminobacter was the lowest in these groups. The relative abundances of both p-75-a5 and Sphaerochaeta were affected by the interaction of starch and sugar. Furthermore, the relative abundance of unidentified_[Paraprevotellaceae], unidentified_S24-7, and Pseudobutyrivibrio was higher in the Hh group than in the Ll group (P < 0.05), while that of Acinetobacter was significantly lower in Hh group than in the Ll group (P < 0.05).At the phylum level, the relative abundance of Bacteroidetes, Proteobacteria, and Spirochaetes was significantly influenced by sugar, and the levels of Bacteroidetes and Spirochaetes in Hh and Lh were higher than those in Ll and Hl groups, whereas the reverse was true for the relative abundance of Proteobacteria . At the P < 0.01; Adonis: R2 = 0.54, P < 0.01). Analysis of similarity also showed that bacterial clusters in the L and H starch groups were distinct, but there were some overlaps in the l and h sugar groups. The results indicated that starch content may have a greater impact on bacterial clusters than the sugar content in the diets.Patterns of variation in the bacterial community composition were observed among groups with different starch and sugar levels using principal coordinates analysis (PCoA). Analysis of similarity based on Bray-Curtis dissimilarity showed significant difference in bacterial clusters between the 4 groups (unidentified_[Paraprevotellaceae] (P < 0.05), unclassified_Clostridiales, and Sphaerochaeta, and gas production was positively correlated with the relative abundance of Ruminobacter (P < 0.05). In the Lh diet, DM digestibility was positively correlated with the relative abundance of p-75-a5 (P < 0.05); acetic acid was positively correlated with the relative abundance of Acinetobacter (P < 0.05); propionic acid and A/P were positively correlated with the relative abundance of Ruminococcus (P < 0.05), which were negatively correlated with the relative abundances of Pseudobutyrivibro (P < 0.05). In the Hl diet, pH was positively correlated with the relative abundances of unidentified_[Paraprevotellaceae] (P < 0.05), DM digestibility was positively correlated with the relative abundance of Pseudobutyrivibro (P < 0.05). And propionic acid and A/P were negatively correlated with the relative abundance of Sphaerochaeta (P < 0.05). In the Hh diet, the relative abundance of p-75-a5 was positively correlated with gas production, acetic acid, propionic acid and A/P (P < 0.05); the relative abundances of Pseudobutyrivibro were positively correlated with acetic acid, propionic acid and A/P (P < 0.05). The relative abundances of Succinictasticum was positively correlated with butyric acid (P < 0.05), but were negatively correlated with pH (P < 0.05).Pearson correlation analysis showed that the relationship between the relative abundances of the differential bacterial at the genus and rumen fermentation parameters within each group . In the The KEGG pathway database is a biological metabolic pathway analysis database. Based on KEGG analysis profiles, 11 endogenous second-level pathways belonged to the following the first-level categories “Metabolism” were considered as potential rumen microbial metabolic pathways .P < 0.05). The relative abundance of Biosynthesis of other secondary metabolites in Lh was higher than that of Hh (P < 0.05). And the relative abundance of Metabolism of terpenoids and polyketides in Lh was higher than that of Hl (P < 0.05). The results revealed that different combinations of starch and sugar affected microbial metabolism, and sugar could increase metabolism, which showed that sugar could not completely replace the role of starch in rumen fermentation.In the six first-level categories, rumen microbial metabolic pathways were mainly enriched in the “Metabolism” category, with Metabolism of cofactors and vitamins , Carbohydrate metabolism , Amino acid metabolism , Metabolism of terpenoids and polyketides , and Metabolism of other amino acids  being the most abundant. The second level categories all belonged to “Metabolism.” These pathways in the Metabolism among the four groups were further analyzed and found that the relative abundance of Amino acid metabolism, Energy metabolism, Glycan biosynthesis and metabolism, Metabolism of other amino acids, Nucleotide metabolism in the Ll and Lh were significantly high than those in the Hl and Hh  produced, there is a lack of factors for absorption of VFAs in the rumen, resulting in the low pH value and accumulation of VFAs in this experiment. Meanwhile, as a result of the higher absorption rate of butyrate than that of acetate and propionate  can be found below: NCBI; The animal study was reviewed and approved by, and all experimental procedures were performed according to the Guidelines for the Care and Use of Experimental Animals of Jilin Agricultural University.G-xQ and Y-gZ contributed to conception and design of the study. XC and X-fZ organized the database. J-nD and S-zL performed the statistical analysis. J-nD wrote the first draft of the manuscript. TW, DW, ZS, and ND wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.XC, TW, ZS, WZ, X-fZ, and Y-gZ were employed by company Changchun Borui Science and Technology Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Currently, society expects convenience food, which is healthy, safe, and easy to prepare and eat in all conditions. On account of the increasing popularity of modified potato starch in food industry and its increasing scope of use, this study focused on improving the physical modification of native starch with temperature changes. As a result, it was found that the suggested method of starch modification with the use of microwave power of 150 W/h had an impact on the change in starch granules. The LF-NMR method determined the whole range of temperatures in which the creation of a starch polymer network occurs. Therefore, the applied LF-NMR technique is a highly promising, noninvasive physical method, which allows obtaining a better-quality structure of potato starch gels. In recent years, one can observe an increased interest in modified starch (starch derivatives). As a natural polysaccharide (biopolymer), starch is  one of tTaking into consideration the biodegradability of starch , for manThe most noticeable modification of starch is chemical modification, which introduces addition functional groups into the system and is met with numerous restrictions as a food additive. However, in the pharmaceutical industry, starch derivatives are versatile compounds, which are commonly used to design systems of delivering medicines . One of It is worth noting that low-field nuclear magnetic resonance (LF-NMR) was used for the needs of this research. Currently, it is one of the most modern techniques of determining surface relaxation in products  during tAccordingly, an endeavor was made to analyze the process of pasting of modified materials with a low-field NMR spectrometer, which works well with determining the dependencies of relaxation times, which in turn pictures the movement of water molecules in the system under research ,31,32. TThe aim of this paper was the physical modification of native starch with temperature changes, as well as the evaluation of influence of the above modification on the process of pasting and creating gel structures in the samples that were subject to analysis. It should be noted that the research was supported by the innovative LF-NMR technique.Potato starch, type Superior Standard (PPZ Trzemeszno), was used for the needs of the research. It should be added that the inlet humidity was set to 35%. Samples of native starch were prepared, which were closed in containers in order to carry out the process of physical modification with a microwave vacuum dryer according to the methods described by Zhang .The research on modifying native starch was carried out using a microwave vacuum dryer Promis Tech. Device as a radiator that uses a magnetron of 2.45 GHz and reaches vacuum at 30–40 kPa. The samples were placed inside the rotary vacuum drum (1), located inside the microwave chamber (2) . Inside The obtained samples were characterized by various degrees of modification and were later used to prepare starch suspensions, which, after heating, became 5% gels. Next, solutions were prepared (10 mL each) consisting of 0.5 g of starch supplemented with distilled water, for both native and modified starch. Suspensions that were obtained were mixed with magnetic mixer in the form of magnets fixed to the work surface. After mixing, all suspensions were left for 24 h. The samples were stored for 24 h in room conditions in order to obtain gruels at room temperature . The above allowed obtaining a stable polymer structure in the samples under research. During that time, the systems were not subject to long-term processes of the retrogradation of amylopectin chains .T1 and spin–spin T2 relaxation times, an impulsive spectrometer H NMR  was used. It should be added that the above device operates at the frequency of 15 MHz and includes an integrated system of temperature control. In order to measure spin–network relaxation times, a shifted impulse sequence and roots were used [T1) were changed from 100 to 6500 ms. The repetition time TR was 20 s, and a single sequence consisted of 32 repetitions. A total of 119 measurement points from each of the 32 FID signals were collected in order to carry out the calculation. Measurements of spin–spin relaxation times were carried out with Carr–Purcell–Meiboom–Gill (CPMG) impulses [In order to determine the temperature changes of spin–network ere used . Distancimpulses ,44,45,46T1 and temperature, which is a classical feature when creating gels from a suspension , a clear decrease in moisture .Demand for hydration water, which is a cause of water shortage in samples, influences the process of expansion and the initial stage of pasting starch granules. For native starch, the initial temperature of pasting is in the 50–60 °C range. Modification with microwaves influenced a decrease in the temperature range. In the case of modification with 50 W/g  and 150 Modification with 50 W/g within the period of 1 min (Despite physical modification by microwave treatment ,48,49,50Additional curve refraction suggests that some water is trapped in crystal structure type A when potato starch granules are subject to the effect of electromagnetic activity. It should be added that changes in the crystal structure in potato starch granules from type B to type A were previously observed . The resUpon analyzing the process of temperature changes, one can observe that the type of modification which shortened the temperature of pasting process to the largest extent also led to an increase in maximum in the last area of heating up samples. One can also conclude that the process of polymer network structure formation was also the longest.Physical modification by microwave treatment of potato starch ,50 does LF-NMR research showed that physical modification by microwave treatment of starch has an influence on the faster reorganization of water molecules, which leads to gel structure formation. Other studies on physical modification by microwave treatment of potato starch proved that such a modification leads to starch becoming an emulsion stabilizer and emulsifier or fat substitute . It shouThe results of this study allow concluding that starch changed its properties as a result of the effect of the electromagnetic field. The use of electromagnetic radiation in starch with 150 W/g led to changes in the structure of starch granules, which permanently changed the hydrophobic and hydrophilic properties. The length of polymer network affected by temperature changes is one of the structural parameters of starch with a fundamental influence on physiochemical properties. Low-field NMR method allows determining the whole temperature range in which the polymer network structure formation of starch occurs. Research with physical factors allows obtaining potato starch modifiers, which, at lower temperatures of heating up, undergo pasting and form a gel structure. This information can be very significant when using starch as a gelling factor in food products, as well as technologically, because one needs a lower temperature when preparing paste.


The Transparency and Openness Promotion (TOP) Guidelines describe modular standards that journals can adopt to promote open science. The TOP Factor is a metric to describe the extent to which journals have adopted the TOP Guidelines in their policies. Systematic methods and rating instruments are needed to calculate the TOP Factor. Moreover, implementation of these open science policies depends on journal procedures and practices, for which TOP provides no standards or rating instruments.We describe a process for assessing journal policies, procedures, and practices according to the TOP Guidelines. We developed this process as part of the Transparency of Research Underpinning Social Intervention Tiers (TRUST) Initiative to advance open science in the social intervention research ecosystem. We also provide new instruments for rating journal instructions to authors (policies), manuscript submission systems (procedures), and published articles (practices) according to standards in the TOP Guidelines. In addition, we describe how to determine the TOP Factor score for a journal, calculate reliability of journal ratings, and assess coherence among a journal’s policies, procedures, and practices. As a demonstration of this process, we describe a protocol for studying approximately 345 influential journals that have published research used to inform evidence-based policy.The TRUST Process includes systematic methods and rating instruments for assessing and facilitating implementation of the TOP Guidelines by journals across disciplines. Our study of journals publishing influential social intervention research will provide a comprehensive account of whether these journals have policies, procedures, and practices that are consistent with standards for open science and thereby facilitate the publication of trustworthy findings to inform evidence-based policy. Through this demonstration, we expect to identify ways to refine the TOP Guidelines and the TOP Factor. Refinements could include: improving templates for adoption in journal instructions to authors, manuscript submission systems, and published articles; revising explanatory guidance intended to enhance the use, understanding, and dissemination of the TOP Guidelines; and clarifying the distinctions among different levels of implementation.https://osf.io/txyr3/.Research materials are available on the Open Science Framework: The online version contains supplementary material available at 10.1186/s41073-021-00112-8. Research transparency and openness can speed scientific progress and increase trust in science . Evidenchttps://osf.io/2sk9f/ for a list of such journals).Published in 2015, the Transparency and Openness Promotion (TOP) Guidelines introduced eight modular standards for transparency and openness: citation standards, data transparency, analytic methods (code) transparency, research materials transparency, design and analysis transparency, study preregistration, analysis plan preregistration, and replication . Using tMeta-scientists can use the modular standards in the TOP Guidelines to evaluate whether journals promote transparency and openness by assessing journal structure, process, and outcomes see Fig. . FollowiTo assess journal policies, the Center for Open Science (COS) created the “TOP Factor” in 2020. Designed as an alternative to the Journal Impact Factor for evaluating journal quality, the TOP Factor is a quantitative metric that assesses the degree to which journal policies promote transparency and openness. The TOP Factor is calculated as the sum of: journal implementation of the eight modular standards within the TOP Guidelines; an additional standard related to publication bias of original studies (rather than replications); and adoption of open science badges  Initiative to advance open science in the social intervention research ecosystem. To demonstrate the application of these processes and instruments, we will evaluate journals that have published social intervention research used by federal evidence clearinghouses, which is research intended to inform evidence-based social policy . We willThe overall TRUST Process for rating journal policies, procedures, and practices according to the TOP Guidelines is summarized in Fig. Although there are no reporting guidelines for a methodologic study of this kind, the TRUST Process follows best-practices for research synthesis that are applicable to our study. For example, we will identify and assess eligible policies, procedures, and practices using methods similar to article identification and data extraction in systematic reviews . We willBefore identifying eligible journals, we searched for federal evidence clearinghouses in a previous study . ClearinIn the current study, we will include all journals that published at least one report of an evaluation used by one federal clearinghouses to support the highest rating possible for an intervention . We will include journals that have changed publisher or changed name since publishing an eligible report. We will exclude journals that have ceased operation entirely.For each eligible journal, two trained graduate research assistants will independently search the journal website for its “Instructions to Authors” and other policy documents. We will identify policy documents that might describe recommendations and requirements related to research transparency and openness. Although open access publishing and preprints are related to transparency and openness, we will not address these issues because they are not addressed in the TOP Guidelines or TOP Factor.To be eligible, policy documents must be publicly available on a journal website or listed on the journal website as available by request . Our objective is to describe each journal’s current policies, which might differ from the policies in place when those journals published research used by eligible evidence clearinghouses. Because our objective is to rate these documents per se, we will not contact editors or publishers to clarify policies that are not described in publicly available documents.For each eligible journal, the graduate research assistants will independently identify eligible documents. Each graduate research assistant will have a folder with their name on Google Drive; for each journal, they will download and save dated copies of websites and other policy documents found on the journal websites . Each pair of graduate research assistants will then meet and compare the identified documents. Disagreements about the eligibility of policy documents will be resolved through discussion. Any unresolved disagreements will be reconciled by consulting the principal investigators and by consulting additional team members during weekly progress meetings. Any additional documents and information regarding journal policies that are identified during the rating process will be downloaded and saved in a subfolder . If policy documents cannot be obtained by searching online, we will contact the journal editors or administrators up to three times to request journal policy documents.We will rate only policy documents that are specific to each journal; although we will note their existence, we will not rate linked policies on external websites. For example, we will consider specific language in journal policies that implements International Committee of Medical Journal Editors (ICMJE) recommendations, but we will not consider a journal policy to incorporate ICMJE recommendations merely by referencing or linking to the ICMJE website. Similarly, we will not rate society or publisher policies that are not specifically incorporated in a journal’s policies because such policies might not be applied equally by all journals affiliated with the society or publisher. For example, American Psychological Association (APA) journals might refer to the APA Publication Manual. We will consider a journal policy to include APA policies that are described specifically in the journal’s instructions to authors and other journal policy documents; however, we will not rate the APA Publication Manual for each APA journal because some APA journals might not incorporate all of its recommendations.For each eligible journal, we will identify procedures that promote transparency and openness. A trained graduate research assistant will initiate a manuscript submission through the journal’s electronic submission system. The graduate research assistant will create a journal account and simulate each submission step in the submission process using blank “dummy” files. They will take screenshots of each step, which they will download and save for assessment. They will download and save submission instructions for journals that do not have electronic submission systems .Because manuscript submission systems might ask questions related to transparency and openness depending on answers to previous questions (“display logic”), the graduate research assistant will answer questions such that all relevant questions and fields would appear. For example, if a manuscript submission system asks whether a study was registered, they will select “Yes” for the purpose of eliciting additional questions about the registration . They will capture all dropdown menus and other options as screenshots. They also will proceed with submission steps without selecting items or filling in fields for the purpose of evoking alerts that would identify which fields are required.All graduate research assistants tasked with identifying journal procedures will discuss issues related to the eligibility of procedures, and issues related to answering questions during the submission process, with each other and with the principal investigators during weekly progress meetings.We will search for articles published in eligible journals between January 1, 2020 and June 30, 2020 (inclusive). For journals in which no eligible articles on intervention research can be found between January 1, 2020 and June 30, 2020, we will search articles published between July 1, 2019 and December 31, 2019. For the purpose of this study, we will consider the date of publication to be the issue to which each article was assigned rather than other dates associated with articles such as the date of acceptance or the date of publication online ahead of print. For example, an article published online ahead of print in December 2019 and appearing in a January 2020 issue would be eligible, while an article published online ahead of print in June 2020 and appearing in the July 2020 issue would be ineligible.Two trained, independent graduate research assistants will screen the titles and abstracts of potentially eligible articles, and they will enter citation information  using a Research Electronic Data Capture (REDCap) form  and are hypothesized to improve health or social outcomes . If no sWe will collect descriptive information about each journal from Journal Citation Reports, 2019 , includiTo develop each rating instrument, the principal investigators drafted a list of questions organized by standards in the TOP Guidelines , 21. To The principal investigators sought feedback about each preliminary rating instrument from colleagues at the COS. Next, the principal investigators trained the graduate research assistants by introducing the project aims, answering general questions about transparency and openness, and discussing each item on the preliminary instruments. The principal investigators then selected a small number of journal policies, procedures, and published articles to be rated by multiple graduate research assistants for pilot testing.During the pilot testing phase for each instrument, graduate research assistants rated a small number of items and then discussed the clarity of the items, instructions, and challenges encountered when rating. Ahead of each weekly project meeting, one project coordinator calculated the proportion of journals with disagreements for each item; the principal investigators reviewed that report and discussed reasons for disagreements and ways to improve the instrument . For each instrument, we repeated the pilot testing process until we had addressed all outstanding questions and obtained satisfactory levels of agreement for all items.We will use the rating instruments to assess policies, procedures, and practices. To assess journal policies, each journal will be assigned to three graduate research assistants to be rated using an online form  graduate research assistants will independently rate procedures and published articles using online forms. The rating form, skip logic and data codebook, and REDCap project XML file for journal procedures are available as Additional files As with journal policies, graduate research assistants will assess journal procedures saved in folders on Google Drive. Instruments for assessing procedures and published articles will focus on the information in those sources only; for example, raters will assess whether articles report that studies were registered and whether data are available, but raters will not confirm each study’s registration status or confirm that they can reproduce the results in an article using publicly available data.During the data collection phase, the team will continue to meet weekly to review and discuss disagreements and to address any new questions or problems that arise with the rating process. Disagreements between raters will be resolved by one of the principal investigators. PIs will review the items where there are discrepancies among the raters and reconcile these disagreements. For each policy, procedure, and practice, we will produce a record with the final ratings for analysis.For each journal, we will calculate the TOP Factor based on the policy rating instrument using an algorithm to determine the level at which each journal follows each standard . We will not assign “levels” to procedures and practices because TOP Factor is designed to evaluate journal policies and does not address journal procedures and practices directly . Instead, we will report whether the journal’s procedure for each standard: does not exist; exists but is not required; or exists and is required. We will then compare the degree to which there is alignment of the journal’s policies with their procedures and practices ; we will not assess IRA and IRR for items that can be skipped. Reliability is a correlational and proportional consistency measure used to determine whether ratings vary between individuals who assess the same thing  and how much of this variability is due to error , 25. AgrWe will assess the IRA using the proportion of overall agreement  and the proportion of specific agreement  , 28. TheBecause each of the standards in the TOP Guidelines is rated using an ordinal scale, we will use the intraclass correlation coefficient (ICC) to evaluate the IRR for each of the standards , 30. ICCThe magnitude of the kappa statistic shows “the proportion of agreement greater than that expected by chance” . The magWe will follow interpretation guidelines developed for ICC (the IRR measure for continuous data) Table  24]. He. He24]. For each instrument , we will calculate the number of items that each graduate research assistant reviewed. For each graduate research assistant, we will calculate the proportion of items on which they agree with the final reconciled ratings as well as the sensitivity and specificity of each of their ratings . Lastly, for the policy instrument, which will be rated by three graduate research assistants, we will also calculate the proportion of items for which each assistant’s rating is in the minority .Because the TOP Guidelines were designed to improve journal policies, and the TOP Factor summarizes the transparency and openness of policies, levels in TOP apply to policies specifically. Consequently, we will present descriptive statistics concerning the concordance of policies with journal procedures see Fig. . We alsoData management will be done in Python   and dataThe TRUST Process provides systematic methods and rating instruments for assessing and scaling-up the appropriate implementation of the TOP Guidelines by journals to which each of the standards in TOP are applicable. By examining a large cohort of influential journals using this process, we will provide a comprehensive account of whether their policies, procedures, and practices are consistent with standards for open science and thereby facilitate the publication of trustworthy findings to inform evidence-based policy.In addition to providing a method for evaluating implementation of the TOP guidelines, we expect that by using this process we will identify ways to refine the TOP Guidelines. Potential refinement could include improving templates for adoption in journal instructions to authors, manuscript submission systems, and article templates; revising explanatory guidance intended to enhance the use, understanding, and dissemination of the TOP Guidelines; and clarifying the distinctions among different levels of implementation.Additional file 1.Additional file 2.Additional file 3.Additional file 4.Additional file 5.Additional file 6.Additional file 7.Additional file 8.Additional file 9.Additional file 10.