Graphene‐field effect transistors fabricated on polydimethylsiloxane substrates reveal an unprecedented hole mobility of ≈21 000 cm2 V−1 s−1 at a gate voltage of −4 V, irrespective of the channel length, which is consistently maintained during the repeat stretching test of 5000 cycles at 140% parallel strain.The direct synthesis of inherently defect‐free, large‐area graphene on flexible substrates is a key technology for soft electronic devices. In the present work, in situ plasma‐assisted thermal chemical vapor deposition is implemented in order to synthesize 4 in. diameter high‐quality graphene directly on 10 nm thick Ti‐buffered substrates at 100 °C. The in situ synthesized monolayer graphene displays outstanding stretching properties coupled with low sheet resistance. Further improved mechanical and electronic performances are achieved by the in situ multi‐stacking of graphene. The four‐layered graphene multi‐stack is shown to display an ultralow resistance of ≈6 Ω sq 2 V−1 s−1, respectively, at VGS = ± 4 V. The Ti–O–C interfacial layer indicated by the density functional theory‐predicted GTO model produces the unprecedented stretchability of the GTO‐FETs during 5000 cycles of parallel stretching of up to 140% strain.Averaged mobility of 42 GTO‐FET (field‐effect transistor) devices indicates high hole and electron mobilities of 21 000 and 12 000 cm In particular, graphene satisfies most of the critical requirements for flexible electrode and device applications and has attracted significant attention. However, the high operation temperature of at least 1000 °C required for the large‐area growth of graphene byconventional chemical vapor deposition (CVD) process hinders the widespread application of graphene‐based electrodes and devices. Moreover, the conventional two‐step process consisting of high‐temperature CVD‐based growth of graphene on metallic substrates and its subsequent transfer onto flexible substrates inevitably generates wrinkles, ripples, and metallic residues that significantly lower the graphene quality. Even the most recent and advanced CVD‐based graphene growth technique demonstrates that the synthesis of large‐area graphene via industrially friendly and versatile CVD is challenging.The leading edge of soft electronics research is driving toward the realization of large‐area and stretchable transparent electrodes and devices that integrate with each other into delicate soft displays, sensors, or energy harvesters.12 In  Based on the results of post‐synthesis analysis and density functional theory (DFT) calculation, the strong Ti–C interaction was proven to generate the required carbon seeds on the Ti and to facilitate the thermodynamically driven spontaneous growth of a graphene monolayer at 150 °C. In previous report, DC‐sputtered Ti‐buffered substrates were moved to the separate CVD system under ambient air for direct graphene synthesis. Because Ti‐buffer layer was naturally oxidized under ambient conditions, the oxidized Ti‐buffer layer was reduced to micrometer size of a clean Ti for various holding times under a reduction atmosphere of H2 at 150 °C. Therefore, the graphene area was limited within the micrometer scale because the graphene grows only on the clean Ti. These results demonstrated the feasibility of the CVD‐based method for the low‐temperature growth of graphene, thus potentially motivating technological advances in relevant fields. However, the high sheet resistance (≈600 Ω sq−1) and narrow size (20 µm × 20 µm) of the graphene synthesized on Ti require further advances to enable the low‐temperature growth of high‐quality, large‐area graphene, which would be applicable to practical soft electrodes and electronic devices.The present authors have previously proposed a possible transfer‐free CVD‐based graphene growth technology by combining the direct current sputtering of a Ti‐buffer layer onto the substrate with subsequent CVD growth of graphene on the Ti.22 BasmGr) on the Ti. The transparent 4 in. diameter mGr directly grown onto the 10 nm thick Ti‐buffered polyethylene terephthalate (PET) and polydimethylsiloxane (PDMS) substrates at 100 °C is shown to exhibit unprecedented stretchable properties combined with an extremely low sheet resistance of 80 Ω sq−1. Moreover, the in situ deposition of multiple mGr layers onto PDMS is shown to further improve the stretchability and decrease the sheet resistance to 6 Ω sq−1, making this product suitable for direct integration into graphene‐based transparent electrodes or electronic devices. Finally, the field‐effect transistors (FETs) constructed from the PATCVD‐grown mGr are shown to exhibit high stretchability along with unprecedented hole mobility of ≈21 000 cm2 V−1 s−1 at a gate voltage of −4 V, which is consistent over a wide range of channel lengths and under repeat stretching tests.In the present work, a two‐step plasma‐assisted thermal chemical vapor deposition (PATCVD) method is developed, which enables the in situ growth of a Ti‐buffer layer onto a target substrate and the subsequent low‐temperature growth of monolayer graphene  confirms that the Ti‐buffer layer controls the mGr growth mechanism. The surface of the mGr is visualized over 50 × 50 µm2 by the micro‐Raman mapping images in Figure I2D/IG and ID/IG. The estimated intensity ratio values I2D/IG = 2.1 ± 0.05 and ID/IG = 0.01 ± 0.008 confirm the superior quality of the PATCVD‐grown mGr. Moreover, the low ID/IG is below the previously reported values for nanometer‐area graphene grown directly on SiO2 substrates via CVD at 800 °C (ID/IG = 0.3) and for transferred single‐crystalline graphene grown on hydrogen‐terminated germanium at temperatures between 900 and 930 °C (ID/IG <0.03). In order to analyze the graphene quality without TiO2−x layer, graphene grown on Ti‐buffered Cu foil was dry‐etched using the dry‐transfer process . The complete removal of TiO2−x layer was confirmed via X‐ray photoelectron spectroscopy (XPS) wide scan  and the etched graphene was transferred to the Cu grid for high‐resolution transmission electron microscope (TEM) analysis. Based on the high‐resolution TEM image  and a selected‐area electron diffraction pattern , the monolayer graphene had an atomically thin, high‐quality graphene lattice. The transferred graphene revealed D peaks by defects formed during the transfer process  and showed an increase of sheet resistance as high as 100 ± 3 Ω sq−1 .As shown schematically in ed value.23 Mor2‐bonded carbon, which revealed the graphene films .Because graphene is grown at high temperatures on various catalytic metals, graphene synthesis at low temperature on titanium has been considered an uncertain process because of the possible formation of titanium carbide on the titanium surface rather than graphene. To eliminate these apprehensions, graphene grown on titanium‐buffer layer at 100 °C was analyzed via XPS, and no titanium carbide was observed , which demonstrated no formation of titanium carbide on a titanium surface at low temperature of 100 °C. The carbon was determined to be spmGr on a flexible substrate, the Ti layer was spontaneously and completely oxidized into semiconducting TiO2−x as the PATCVD‐grown mGr was exposed to ambient conditions. This is confirmed by the typical TiO2−x feature in the X‐ray photoelectron spectra of the mGr grown at 100 °C and subsequently exposed to air . Therefore, the mGr is supported on TiO2−x and is referred to hereafter as GTO. Sufficient experimental evidence of metal oxidation in the case of CVD‐graphene on a Cu catalyst occurred when molecules penetrated the graphene grain boundary and diffused laterally along the graphene–metal interface. As indicated by the above‐mentioned results, this semiconducting TiO2−x layer does not exert any negative effect on the conductivity of the PATCVD‐grown mGr.In the present work, although a metallic Ti‐buffer layer was used to grow the large‐area  The polarized optical microscopy (POM) images in Figure The distribution and size of the graphene domains synthesized directly on Ti (10 nm)‐buffered PDMS substrates at 100 °C were demonstrated by imaging the birefringence of a GTO surface covered with well‐known nematic liquid‐crystal molecules (5CB: 4‐pentyl‐4’‐cyanobiphenyl) in accordance with previous studies.30 ThemGr on a Ni catalytic metal have shown the grain size to be a positive function of the growth temperature and to be highly dependent on the Ni grain size due to the surface‐reaction‐controlled mechanism (activation energy of 0.52–0.77 eV). Based on the distribution of graphene domains observed in the POM image  reveals a significantly decreased growth activation energy of 0.28 eV, which is a distinctive feature of a mass‐transport‐controlled thin‐film growth mechanism, which demonstrated a large domain size of monolayer graphene grown at low temperature. Improvement of growth rate can be achieved by a sufficient supply of carbon source because our graphene growth was controlled by a mass‐transport mechanism.Previous studies on the growth of 0.77 eV).32 Base Figure , an aver its inherent mechanical and electronic superiority are diminished by conventional CVD and transfer methodology because structural defects are generated upon transfer and the transferred graphene cannot strongly adhere to the flexible substrate. Because graphene has a strong carbon–carbon in‐plane network, the upper stretching strain limit at which the CVD‐grown graphene transferred onto a PDMS can recover its initial conductivity is only 6%. Moreover, the initial conductivity of conventional PDMS‐supported graphene under an applied strain perpendicular or parallel to the current flow is maintained only at less than 11% strain. By contrast, since the PATCVD technique used in the present work allows the in situ deposition of GTO on a stretchable substrate, enhanced stretchability of the GTO is anticipated.Although graphene is expected to find wide application in flexible electronic devices,23 itsFigure R − Ro)/Ro) at values of less than 10 for stretching strains of up to 60% for a 70 µm × 15,000 µm GTO strip grown onto a 3.0 cm × 4.0 cm PDMS substrate. Moreover, even at 70% strain, the perpendicular (R − Ro)/Ro was controlled at around 10, which is the general upper limit for graphene stretching‐resistance tests. In addition, an LED switching test was performed to visually demonstrate the outstanding performance of the GTO/PDMS as a stretchable electrode, as shown in Figure The results presented in  For example, Lee et al. reported breaking strengths of ≈91 and 118 GPa for graphene with domain sizes of ≈2.5 and 200 µm, respectively. Hence, because the domain size of the GTO samples prepared in the present work is generally larger than 260 µm  mapping image and spectra (C K‐edge and Ti L‐edge) of the GTO in Figure Eint) was reduced from −11.5 eV nm−2 between mGr and Ti to −0.4 eV nm−2 between the mGr and TiO2−x of the GTO model. Taken together, the EELS and DFT results suggest that the GTO is a layered composite material consisting of mGr floating on TiO2−x.As indicated by Figure S8 in the Supporting Information, the area‐normalized DFT‐calculated interaction energy /Ro responds to the parallel strain. As indicated in Figure S9 in the Supporting Information, the transferred graphene revealed an extreme (R − Ro)/Ro increase at 60% strain, thus confirming the advantage afforded by the graphene–TiO2−x interfacial layer for improved stretchability of the GTO. Overall, these results demonstrate that the combined effects of domain size and facilitated graphene sliding at the mGr‐TiO2−x interface lead to the mechanical and electronic supremacy of the PATCVD‐grown GTO.The interface between Figure nGTO, where n is the total number of stacked GTO layers) and the corresponding photographic images (insets) presented on the right‐hand side of Figure  thus confirming that the TiO2−x layer has no significant influence on the transmittance. As shown in Figure 10 in the Supporting Information, the mGr was preserved in each individual stacking layer, so that the mGr layers of the nGTO were sandwiched between successive TiO2−x layers.The resistance of the GTO was further reduced by the direct in situ stacking of up to four GTO layers at 100 °C on a flexible substrate, as shown schematically on the left‐hand side of f Figure 23 thu−1 for the 4GTO which, along with the high transparency of 90.8%, is superior to the previous best results. Even the lowest reported resistance of a transferred four‐layer graphene system (≈30 Ω sq−1) is five times greater than that of the present 4GTO. This remarkable decrease in the resistance upon GTO multi‐stacking is attributed to the nondestructive charge transfer p‐doping by oxygen adsorbed on the mGr of each stack, which is revealed by the gradually increasing positive shift in the Dirac voltage of the nGTO‐FETs in Figure  By contrast, no notable Dirac shift was observed in the single‐layer GTO‐based FET, thus suggesting that p‐doping is induced by the TiO2−x interlayer sandwiched between two mGr layers in the GTO multi‐stack. In addition, the results in Figure S11 in the Supporting Information demonstrate that the self‐p‐doping effect of multilayer nGTO is not degraded by high‐temperature treatment.The Z‐theta, van‐der‐Pauw, and four‐point probe measurements presented in Figure 30 Ω sq−123) isnGTO is naturally more rigid than the single‐layer GTO. Nevertheless, Won et al. reported that transferred multilayer graphene displayed excellent stretchability due to the strain relaxation facilitated by sliding among the graphene layers, such that bi‐ or tri‐layered graphene stacked by a transfer process was stretchable by up to 30% strain. Indeed, the (R − Ro)/Ro ratios obtained from the single‐cycle stretching test /Ro ratios of less than 10 were maintained for the 4GTO under single cycles of up to 70% and 80% strain parallel and perpendicular to the current direction, respectively . However, the critical dimensional regulation of graphene‐FET channel length interferes with the high‐density integration of the graphene‐based devices, thus diluting the practical value of graphene.Because transferred graphene is rich in defects, its FET mobility increases in direct proportion to the channel length.42 Mor2 and Al2O3. In the present work, the channel length of the GTO‐FETs was varied between 10 and 100 µm at a fixed channel width of 20 µm, especially, the defect‐free nature of the GTO made it possible to decrease the channel length to 10 µm. Considering the inherent interface‐related contact issues in FETs, a gated‐transfer line method was applied to appropriately estimate the mobility as a dependency of the channel resistance to the channel length . For the GTO‐FET with a 20 µm × 20 µm channel (length × width), the drain current–gate voltage and gate current–gate voltage profiles in Figure VGS = ± 10 V. Meanwhile, the output characteristics shown in Figure 2 V−1 s−1, respectively, at a VGS = ± 4 V. Notably, this hole mobility higher than the previously reported values of 11 000 and 3000 cm2 V−1 s−1 for fold‐free transferred single‐crystal graphene with channel lengths of 100 and 8 µm, respectively. Moreover, the consistent high mobility, which does not vary with the channel length, confirms that the GTO‐FETs can be directly applied to nanometer‐scale graphene‐FETs, thus overcoming the defect density‐related channel length regulation issue. As shown in Figure In the present work, a stretchable bottom‐gate‐FET device with gate, active layer, and source/drain electrodes was constructed using the GTO grown at 100 °C on a stretchable PDMS (200 µm) substrate with a polyimide (120 nm) gate dielectric. Fully imidized aromatic polyimide is well known as an organic gate dielectric for flexible FETs because of its excellent chemical and electrical stability as well as flexibility compared with brittle inorganic insulators such as SiOnd Al2O3.44 In mGr on Ti‐buffered stretchable substrates without the need for a transfer step. The resulting GTO and nGTOs revealed ground‐breaking mechanical performance coupled with consistent and excellent electronic properties. These properties were confirmed by the fully stretchable GTO‐FET, which displayed high and consistent mobility irrespective of the channel length. The methodological advance achieved by the use of PATCVD for the low‐temperature growth of large‐area, high‐quality graphene provides a technological breakthrough toward the realization of graphene‐based soft devices and next‐generation nanometer‐scale FETs.In summary, the in situ PATCVD method was implemented to directly synthesize The authors declare no conflict of interest.Y.H., B.‐J.P., and J.‐H.E. contributed equally to this work. S.G.Y. planned and supervised the project; Y.H., B.J.P., J.H.E., and S.G.Y. designed and performed the experiments, and characterized the electrical properties of graphene; V.J., S.I., and S.V.N.P. fabricated the PDMS substrate and designed the LED circuit; J.S.C. analyzed the crystallinity and phase of the graphene; H.H., H.C., and H.Y.K. performed DFT calculations; C.J. analyzed in situ deposited Ti metal via XPS; K.P., H.T.J., S.Y., Y.H.K. analyzed the grain size of the graphene using liquid crystal films; H.Y.K., Y.H.K., S.G.Y. analyzed the results and wrote the manuscript.Supporting InformationClick here for additional data file.Supplemental Video 1Click here for additional data file.Supplemental Video 2Click here for additional data file.


Eighteen preadolescent swimmers (12.2 ± 0.4 years old and 3–4 Tanner stages) underwent 4 weeks of systematic contextual interference training, comprising 16 sessions (40 min·session−1). Soon after, experimental testing was conducted where swimmers randomly performed 12 × 15 m maximal turns , three in each transition technique. Kinematical, kinetic, and hydrodynamic variables were assessed with a dual-media motion capture system (12 land and 11 underwater cameras), triaxial underwater force plates, and inverse dynamics. Variables were grouped in turn-in (approach and rotation) and turn-out  phases, with factor analysis used to select the variables entering on multiple regressions. For the turn-in phase, 86, 77, 89, and 87% of the variance for open, somersault, bucket, and crossover turning techniques, respectively, was accounted by the 7.5 and 2.5 m times, mean stroke length, and rotation time. For the turn-out phase, first gliding distance and time, second gliding depth, turn-out time, and dominating peak_Z push-off force accounted for 93% in open turn, while wall contact time, first gliding distance, breakout distance and time, turn-out time, dominating peak_Y push-off force, and second gliding drag coefficient accounted for 92% in a somersault turn. The foot plant index, push-off velocity, second gliding distance, and turn-out time accounted for 92% in bucket turn while breakout and turn-out time, non-dominating peak_Y and peak_Z push-off force, first and second gliding drag force and second gliding drag coefficient accounted for 90% in crossover turn, respectively. The findings in this study were novel and provided relevant biomechanical contribution, focusing on the key kinematic–temporal determinant during turn-in, rotation, and push-off efficacy, and the kinetic and hydrodynamic during turn-out, which would lead to improved backstroke to breaststroke transition techniques in 11–13 years-old age-group swimmers.This study aimed to identify the biomechanical features of backstroke to breaststroke transition techniques ( Performing fast and skilled turning actions, and start and swim phases, is fundamental for improving competitive swimming performance , which are very complex movements . In addition, swimmers need to comply with the FINA rules, i.e., touch the wall while on their back, maintain the shoulders at or past the vertical direction toward the breast when leaving the wall, and assume a ventral gliding position prior to the first breaststroke upper limbs action. Studies on the backstroke to breaststroke transition techniques are scarce, lacking scientific and practical validation of the specific determinant factors that play a vital role in gaining the advantage in each backstroke to breaststroke transition techniques.Among the medley turns, there are four well-described backstroke to breaststroke transition techniques : 12.5 ± 0.5 vs. 11.6 ± 0.5 years old, 48.7 ± 12.4 vs. 46.7 ± 10.8 kg of body mass, 1.59 ± 0.14 vs. 1.52 ± 0.07 m of height, 14.8 ± 5.1 vs. 21.8 ± 7.10% of fat mass, 3–4 Tanner stages  and a full-body marker setup  acquisition, plotting, and saving the strain readings of each triaxial force and the moment-of-force components from each force plate using a custom LabVIEW™ program   encompassed approaching, touching , rolling, pushing glide, and swimming resumption until the vertex passes the 7.5 m marker . The Quapost-hoc pairwise comparisons using Tukey's HSD were conducted. Then, factor analysis was conducted to lower the number of variables and to analyze the relationships structures between variables. For this purpose, selected variables were grouped into turn-in and turn-out variables , factors were chosen on the basis of a cutoff eigenvalue of 1, principal component extraction with a varimax rotation, and the scree plot proposed  aiming to detect potential errors in data entry and eventual outliers, and assessing data distribution normality (Shapiro–Wilk test), multicollinearity (variance inflation factors), and homoscedasticity (Levene's test). A one-way ANOVA was used to observe differences in the selected kinematic-temporal, kinetic, and hydrodynamic variables among the four different backstroke to breaststroke turning techniques. If a significant effect was found, p = 0.61), rotation time , turn-out , and 15 m turn times .Descriptive- and variance-related analysis on selected variables for each backstroke to breaststroke turning technique is given in open turn, there were three predictors  explained 86%  for turn-in, five predictors  explained 93%  for turn-out on the 15 m turning time. For the somersault turn, there were three predictors  explained 78%  for turn-in, seven predictors  explained 92%  for turn-out on the 15 m turning time, respectively.The best subsets regression for turn-in and turn-out to predict 15 m turning time in each backstroke to breaststroke turning technique are given in bucket turn, there were three predictors  explained 89%  for turn-in, five predictors  explained 92%  for turn-out on the 15 m turning time. For the crossover turn, there were four predictors  explained 87%  for turn-in, seven predictors  explained 90%  for turn-out on the 15 m turning time, respectively.For the open, somersault, bucket, and crossover) in age-group swimmers. We believed that 15 m turning time performance is described by combining contributions from the turn-in and turn-out phases, and different combinations of feature variables depending on the chosen backstroke to breaststroke transition technique. As expected, general turn-in performance can be predicted mostly by faster times during the 7.5 m, 2.5 m to the wall. The average SL is a predictor of turn-in performance for both open and crossover turns, with faster rotation time being the most relevant variable for somersault and crossover turns. The last upper limbs-to-wall distance, which refers to kinesthetic awareness and sense of space, affects bucket turn performance. Our results from the turn-out phase highlighted the importance of the interaction between kinematic and kinetic variables at the wall contact and push-off phase, which influenced turn-out performance across all backstroke to breaststroke turns studied. However, the importance of the turn-out variables changes depending on the chosen technique.The main aim of this study was to identify the biomechanical features of backstroke to breaststroke transition techniques  and the four kinematic-temporal variables . Theoretically, the peak perpendicular force, total impulse, and wall contact time kinetic features are key factors of swimming turns  and rotation time. Given the high impact of the turn-in phase on the 15 m turning performance, the swimming approach (7.5 m and 2.5 m turn-in times), and rotation times should be more deeply considered. The somersault turn, compared to the open turn findings, suggests that a faster approach could directly influence the turn time. Since the execution of the somersault turn requires a hand touch at the wall before rotating from the supine to the prone position, the rotation is critical. At this backstroke to breaststroke transition, the rotation time tended to be slightly slower than those previously studied in the rollover backstroke  variables were those affecting the 15 m turn time. Based on the pull-out strategy evidence, breakout distance, breakout time, and turn-out time were identified as the important variables, indicating that age-group swimmers should select their own individual strategies by considering the breakout distance and the time to maximize the pull-out performance , dominant push-off peak_Y force  was selected as a critical predictor of the 15 m turn time. Theoretically, the push-off force with the feet pushing up or down directly affects the push-off velocity and tends to be inversely related with rollover time  and 2.5 m time-in (r = 0.85), and a small inverse relationship between 15 m turn time and last upper limbs-wall distance (r = −0.13). As in the open and somersault turns, speed-in was an essential influencing factor of turning performance, in agreement with the previous literature on elite  variables were identified as the key variables for the backstroke to breaststroke turning performance. From the perspective of push-off efficacy, it is advantageous to address the appropriate lower extremity at wall contact with a greater tuck index and optimal feet planting (30–40 cm depth), which will facilitate the best horizontal push-off velocity  and CD, and D values for the same range of speeds  a worst streamline performance due to the lateral body movements that occur from the wall push-off to the first gliding position may , and the hydrodynamic variables are important for all the studied transition techniques. Finally, the rotation and push-off phases were the stronger determinants of turning performance among all studied backstroke to breaststroke turns. Considering the key biomechanical variables that influence each turning performance in the current data, the development of a specific training program aiming to enhance turning skills, particularly focusing on the rotation and push-off phases, should be reconsidered by coaches who work with age-group swimmers, even if it implies in a longer training intervention.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Faculty of Sport, University of Porto. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.PC, RZ, RF, and JV-B: conceptualization, methodology, writing—original draft preparation, and project administration. PC, KJ, RZ, LM, and PF: data curation. PC, KJ, LM, PF, RZ, RF, and JV-B: review and editing. PC and RZ: visualization. JV-B: supervision. All the authors have read and agreed to the published version of the manuscript.This study was supported by the Faculty of the Sport Science, Burapha University, Thailand (grant number 062/2554). RZ was founded by Research Center in Physical Activity, Health and Leisure—CIAFEL—Faculty of Sports, University of Porto—FADEUP , Porto, Portugal (LA/P/0064/2020).The 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.


To compare the influence of objective and subjective measures of the three learning programs  on resident test performance and study platform preference.Sixty residents from three orthopaedic residencies were included in this study during May 2020. Trauma, pediatrics, and hip/knee reconstruction (joints) were chosen as testing topics. Residents took a standardized pretest of 30 questions per topic, followed by the completion of 50 questions per day for 5 days using one of the three web-based programs, followed by a standardized subject-specific posttest. This cycle was repeated for all the three topics. Bivariate statistics and a mixed-effects linear regression model were used to compare improvements in the scores.P < 0.001): 6.8% higher with OB, 5.4% with RS, and 1.0% with CC. The score improvement with OB was significantly greater than the score improvement with CC (P < 0.001). In total, 100% of residents reported that using OB would improve their score on the orthopaedic in-training examination, compared with 95% with RS and 67% with CC.Across all learning platforms, topics, and postgraduate year classes, posttest scores were 4.4% higher than the pretest score (73.3% vs. 68.9%, OB demonstrated the greatest improvement in scores, followed closely by RS and then CC. Because the Accreditation Council for Graduate Medical Education monitors every residency program's board pass rate, programs have a vested interest in identifying tools to track resident education progress and promote effective learning strategies.2-4For graduating residents in the United States, board certification examinations are very important and are heavily regulated to ensure that competency standards are maintained.2 Established in 1963 by the American Academy of Orthopaedic Surgeons (AAOS), the OITE is administered annually and serves as a tool that allows programs to assess their residents and identify individuals at risk of failing the ABOS examination.5 Over the last decade, several online question banks—including Clinical Classroom (CC), OrthoBullets (OB), and ResStudy (RS)—have been developed with the ultimate goal of promoting long-term information retention through reinforced cycles of information processing and retrieval.6-8 The relative utility of each of these resources in improving OITE test scores among orthopaedic residents has not been investigated.Currently, the orthopaedic in-training examination (OITE) is the primary objective assessment of resident knowledge throughout training and is highly predictive of performance on ABOS part I written examination.9 The primary purpose of this study was to compare objective measures of the top three learning web-based programs OB, RS, and CC for OITE performance. A secondary objective of this study was to use a survey to determine subjective resident preference of these three learning platforms. We hypothesized that, objectively, all three web-based programs would increase a resident's score and that, subjectively, there would be an equal distribution of residents preferring each study platform.Identification of optimal learning strategies and preparation resources available to orthopaedic surgery residents can improve their performance on the OITE, which may translate to superior clinical performance.This was a prospective cohort study of resident orthopaedic surgeons from three US allopathic orthopaedic residences during May 2020. Residents in postgraduate years (PGY) 1 to 4 were included in our analysis. PGY-5 residents were excluded from our study design because of concurrent preparation for ABOS part I written examination during the period in which this study was conducted. Because each residency program had six residents per PGY class, a total of 72 residents met the initial inclusion criteria.Residents were divided into three separate groups , each composed of members from all included PGY classes. All groups were assigned to a 15-day study schedule, which was subdivided into 5-day blocks corresponding to one of the three specific OITE topics. Each block consisted of a 30-question pretest on a single topic, followed by 50 questions completed daily on an assigned learning platform, and finally a 30-question posttest at the conclusion of each block Table . Group sOf the 72 residents who initially met the inclusion criteria, 39 (54%) completed the study plan in its entirety, 12 (17%) residents completed two platforms, 9 (13%) residents completed only one platform, and 12 (17%) residents completed none of the platforms. After excluding the residents who completed none of the study platforms, a total of 60 residents and 300 test scores (150 pretests and 150 posttests) were included in our final cohort.Three topics were chosen for this study: trauma, pediatrics, and joints. These topics represent the most highly tested material on OITEs from 2015 to 2019 Table . Shoulde10 The OB authors typically consist of resident physicians who achieved at least one >90th percentile OITE scores based on PGY class. Each question undergoes a rigorous peer-review process consisting of two independent reviewers with multiple stages of edits and strict tested content criteria.10 The review content is multimodal and includes case-based learning, videos, operative techniques, and discussion forums. OB includes a curriculum across various orthopaedic topics, with the ability to track daily progress through the material and a proprietary machine learning–enabled spaced repetition algorithm, called Anconeus, which provides users with daily learning question reinforcement.10Three learning platforms were evaluated in this study as follows: OB, RS, and CC. OB was developed in 2011 and currently has over 7,000 questions available from multiple sources including 2007 to 2013 AAOS self-assessment examination (SAE) questions, OITE-based questions (OBQ), and SAE-based questions (SBQ). OBQ and SBQ are generated internally from the OB authors.11 However, RS typically explains the rationale for answer choices by citing previously published literature to adequately explain the tested concept.RS was introduced in 2012 and has approximately 5,000 questions available for users. These questions are taken from previous 2012 to 2019 OITEs, 2015 to 2020 SAE questions, and previous Orthopaedic Knowledge Update examinations. Similar to OB, RS also offers residents the ability to select topics for testing and the ability to track the examination history and progress but does not offer a comprehensively structured educational curriculum.12 Although the residents participating in this study had access to OB and RS for several years, access to CC was obtained just before this study.Finally, CC was developed in 2017 and uses adaptive algorithms to reinforce learning based on user input regarding the perceived difficulty level for each question. After every answered question, users rank their subjective level of confidence with one of the four labels: (1) know it, (2) think so, (3) unsure, and (4) no idea. Using this information, proprietary adaptive learning algorithms generate question sets that continually test areas of weakness. CC has approximately 3,500 questions, all generated from well-known experts across various orthopaedic subspecialties. Similar to OB and RS, CC offers users the ability to filter questions by topic.Sixty questions for each topic  were randomly selected from the 2007 to 2013 AAOS SAE examinations found on the OB question database. Each set of 60 questions was divided equally into two sets, a pretest and a posttest. Question difficulty between the pretests and posttests was matched for each set of examinations based on the average percentage of OB users who answered a given question correctly. Considering the large sample size of OB users per question, this method served as a proxy for question difficulty. For participants who used OB as a learning platform, 2007 to 2013 SAE questions were deselected from the question bank in all user accounts so that all practice questions only consisted of OB generated OBQ and SBQ only. This way, we ensured that all pretest and posttest questions were curated from previous subject-specific SAE which were not available in any of the three web-based learning platforms and that no learning platform offered residents an unfair advantage. One PGY-5 resident (S.M.) reviewed the pretest and posttest questions to ensure that the most testable and appropriate topics were included.classmarker.com .13-15 The response data were downloaded directly from the website. All residents who completed the study were given the option to complete this survey. Participation in the survey was voluntary. The questions assessed resident perception of each learning platform's quality, efficacy, and relevance in relation to the in-training examination. These questions also assess what kinds of learning strategy residents were used to study for the in-training examination in the past and what they prefer to use in the future if given limited resources.An anonymous 22-question survey was developed based on surveys used in similar studies and constructed in t-test, paired samples' t-test, and one-way analysis of variance with post hoc analyses were done where appropriate. Because some residents only completed one or two of the platforms while others completed all three, we incorporated a mixed-effects generalized linear regression model to control for (1) inherent differences in test-taking ability between residents, (2) different pretest scores between PGY-classes, and (3) differences in percentages across the study topics. Based on our study design, test scores were nonindependent observations because each resident could account for more than one test score in different topics or learning platforms. In other words, test scores from all three study platforms and all three topics were compiled from tests taken by the same cohort of residents, making these test scores nonindependent of each other. As such, a mixed-effects model was chosen to account for both fixed and random effects stemming from the nonindependence within our data set that was inherent to our study design. Statistical significance was set at P = 0.05. Statistical analyses were done with the assistance of a statistician using STATA version 15.0 .A power analysis was done demonstrating that 150 pretests and 150 posttests were needed to detect a 5% difference between pretest and posttest scores with 80% of power. For bivariate analyses, independent samples' P < 0.001; Figure P < 0.001), but there were no significant differences in comparison between any other study platforms , followed by trauma (4.3%) and joints 2.9%) .On unadjusted analysis, there were no significant differences in score improvement between the PGY classes across all study platforms .At the completion of the study, 32% of all residents (23) responded to the survey. When asked to choose a single study resource, 52% (12) of residents chose OB, 48% (11) chose RS, and 0% (0) chose CC. On average, residents rated OB as 9 of 10, RS as 8 of 10, and CC as 5 of 10. In total, 100% of residents (23) thought that studying using OB would improve their score on the OITE, compared with 96% (22) with RS and 65% (15) with CC. When asked to rank the ease of use, 52% of residents (11) ranked OB first, compared with 43% (10) with RS and 5% (1) with CC . Positive comments for each learning platform included “OB has best explanations and well-designed Anconeus spaced repetition tool,” “ResStudy has the most recent OITE questions and is most similar to OITEs,” and “CC has multiple types of questions, not just multiple choice, along with their Recharge spaced repetition tool.” Criticism of each learning platform included “OB only has older SAE questions and no OITE questions,” “ResStudy has no repetition learning and does not provide explanations for all questions,” and “CC is not similar to OITE questions and has limited number of questions compared with other platforms.”Free response resident feedback was collected to comprehensively evaluate the likes and dislikes of each learning platform .Residents were also asked to provide preferred learning platforms and additional study resources used to prepare for the 2019 OITE  within a given program is required to maintain program Accreditation Council for Graduate Medical Education.12 In our survey, residents noted this difference between CC questions and OITE questions. In contrast to CC, RS uses questions from recent OITEs and SAEs and is thus more representative of an OITE for the question style and content.11 Although OB does not incorporate any actual previous OITE questions, OB offers OBQ and SBQ questions which are specifically designed by the OB authors to mirror OITE questions.10 Because our posttests were generated from a random sample of 2007 to 2013 SAE questions, CC questions may not have approximated standardized exam questions as accurately as OB or RS, leading to poorer posttest performances.The differences in effectiveness between the three study platforms may be explained by how well each study platform's practice question approximates OITE questions. CC, which was associated with the lowest score improvement, contains questions derived from panels of experts, rather than from previous OITEs.8 In a randomized controlled trial of 65 pediatric and emergency medicine residents, Larsen et al.6 demonstrated that study participants who focused on practice questions had markedly greater long-term retention of information than those who passively reviewed the material. However, the way in which practice questions are incorporated into a learning style can add to the effectiveness of any learning strategy and may explain, in part, why the largest score improvement was seen in OB. OB uses a proprietary repetition algorithm which continually tests areas of weakness in a systematic way that promotes active recall and long-term retention. In several studies, this type of “spaced-repetition” has been demonstrated to reinforce neural patterns and improve recall.12 CC also incorporates an automated repetition algorithm that serves to improve long-term retention. RS does not currently include a repetition algorithm, which was noted as a shortcoming of the platform based on survey comments. Ultimately, it is likely that both the similarity of OB practice questions to OITE questions and the robustness of its Anconeus spaced-repetition algorithm collectively contributed to its effectiveness and preference as a study tool compared with CC in our resident population.All three study platforms included in our study used practice questions as the primary study strategy, which has been shown to be effective for long-term information retention.17 Because of stay-at-home orders during the pandemic, we were unable to strictly enforce the completion of practice questions across learning platforms or the poststudy questionnaire among our resident cohort. As such, only 39 of 60 (65%) of residents completed the study plan in its entirety, and 23 of 60 (32%) completed the poststudy questionnaire, which may limit our ability to draw notable conclusions from the data set. Moreover, although we requested residents to use their assigned learning platform, we were unable to verify this during each block of the 2-week study period. Finally, because participants were aware that they were being observed during the study period, they were susceptible to the Hawthorne effect, which may have influenced their performance on pretests and posttests. Additional investigation focusing on the effect on actual OITE and/or ABOS part I scores in relation to each platform may be valuable. Additional studies may also evaluate which learning platforms or components have the greatest effect on establishing a foundational knowledge base and potentially superior clinical performance.The results of this study must be interpreted in context of its limitations. First, our pretest and posttest questions were derived from OB 2007 to 2013 SAE questions, and although there was no overlap of years with the 2015 to 2020 SAE questions on RS, we cannot be certain that some older SAE questions did not appear on the newer forms, although this situation would be highly unlikely. Moreover, the relatively small sample size of 250 questions per subject topic may limit the significance of our results; however, because of time constraints of didactic learning in the pandemic, we were unable to ask residents to complete more than 50 questions daily. Extraneous testing factors—such as location and concurrent work schedule—may have affected resident performance on pretests and posttests and were not accounted for in our study design. It is also possible that residents' lack of familiarity with CC relative to OB and RS may also have contributed to the findings. In addition, it is important to note that individuals have unique learning styles and may benefit differently from various question-based study platforms. Although question-based study platforms were tested, it is still critical for residents to use other resources for a solid core knowledge base. However, in our study, OB resulted in the best posttest improvement that does not necessarily correlate with a better comprehensive knowledge base. CC promotes using a metacognitive approach to improve critical thinking and complex decision making, with a focus on mastery and reinforcement more so than answering test questions. This overall study design was particularly unique because it involved residents from three different residency programs across a span of 2 weeks. A major factor as to why this was accomplished in May 2020 was because of the cancellation of elective cases and adoption of a modified resident schedule during the first wave of coronavirus disease 2019.OB demonstrated the greatest improvement in scores, followed by RS and then CC. These results provide useful information and insights for residents and residency programs seeking optimal learning resources for OITE preparation.


To investigate the diagnostic and staging value of serum angiotensin-converting enzyme (sACE) in sarcoidosis.  Patients with suspected sarcoidosis treated in the Department of Pulmonary and Critical Care Medicine of the China-Japan Friendship Hospital from 2010 to 2020 were included. The data of sACE, erythrocyte sedimentation rate (ESR), complete blood count (CBC), lung function, bronchoalveolar lavage, and biopsy were collected. The differences between the sarcoidosis group and the nonsarcoidosis group and between different stages of sarcoidosis were compared. The receiver operating characteristic (ROC) curve analysis was used for the diagnostic test of sACE in sarcoidosis. P = 0.001). The level of sACE in sarcoidosis patients with peripheral superficial lymph nodes and multiple system involvement was significantly higher than that in intrathoracic sarcoidosis patients (P = 0.009); the percentage of lymphocytes in bronchoalveolar lavage fluid (BALF) of sarcoidosis patients was 45.39 ± 22.87%, which was significantly higher than that of nonsarcoidosis patients (P < 0.001). There was no correlation between sACE and ESR (correlation coefficient = −0.167). According to ROC curve analysis, when sACE ≥ 44.0 U/L, the sensitivity of sarcoidosis diagnosis was 61.4%, the specificity was 92.9%, and the AUC was 0.819.  A total of 84 cases with suspected sarcoidosis were included, among which 70 cases were confirmed to be sarcoidosis by biopsy. The mean value of sACE in sarcoidosis patients was 56.61 ± 30.80 U/L, which was significantly higher than that in nonsarcoidosis patients (28.07 ± 14.11 U/L,  sACE has a good specificity in the diagnosis of sarcoidosis. sACE values in patients with sarcoidosis with systemic involvement were higher than those with simple intrathoracic sarcoidosis. Sarcoidosis is a multisystemic granulomatous disease of unknown etiology. Pulmonary involvement is most frequent in sarcoidosis patients, while extrathoracic involvement occurs in only 30% of cases –4. It haβ-amyloid peptide (Aβ) 42 into Aβ40 in the human brain, and its conversion activity is mediated by two catalytic domains [At present, increasing research results indicate that serum markers are of great value in disease diagnosis and prognosis prediction, with advantages of simple sample collection, minimal invasiveness, low cost, high sensitivity, and specificity , 10. Cli domains . sACE, w domains . This suThis study prospectively included patients with suspected sarcoidosis hospitalized in the Department of Pulmonary and Critical Care Medicine of the China-Japan Friendship Hospital between 2010 and 2020. A total of 84 cases of suspected sarcoidosis were included, 70 cases of which were histopathologically confirmed. Among them, 9 cases were confirmed as lymphatic tuberculosis, 2 cases as malignancy, and 3 cases as other diseases that cause enlargement of mediastinal and hilar lymph nodes. According to the histopathological diagnosis, 70 patients with sarcoidosis were assigned to the sarcoidosis group, and the remaining 14 patients were assigned to the nonsarcoidosis group. Almost all the cases presented with cough, expectoration, chest tenderness, or shortness of breath, while fever as well as fatigue and weight loss were observed in 18 and 19 cases, respectively.Patients meeting one of the following criteria were considered suspected sarcoidosis: (1) chest radiograph or computed tomography showing bilateral or unilateral hilar or mediastinal lymphadenopathy, with or without pulmonary opacities; (2) on the basis of (1), patients presented with respiratory symptoms such as cough, dyspnea, and chest pain, accompanied by fatigue, malaise, fever, or weight loss; and (3) other conditions that cannot exclude sarcoidosis as confirmed by a respiratory physician.The diagnostic criteria of sarcoidosis were based on the following: (1) consistent clinical and radiographic findings, (2) histopathologic detection of nonnecrotizing granulomas, and (3) exclusion of other diseases.n = 14, 20.00%), stage II group , and stage III group , with no stage IV patients. Furthermore, sarcoidosis patients were assigned to the intrathoracic sarcoidosis group , sarcoidosis-involved intrathoracic organ and peripheral lymph node group , and multisystemic sarcoidosis group  based on the location of nodular involvement. Among extrathoracic sarcoidosis, there were 2 cases of skin involvement, 4 cases of hepatic involvement, 3 cases of splenic involvement, 3 cases of ocular involvement, and 1 case of cardiac involvement.Sarcoidosis patients were staged for the disease according to the Scadding system of staging : stage IWritten informed consent was obtained prior to data collection. The study was approved by the Ethics Committee of China-Japan Friendship Hospital.sACE: the peripheral blood serum was collected from patients to detect sACE using an ultraviolet spectrophotometer.Complete blood count (CBC): CBC, including white blood cell count (WBC), lymphocytes, and hemoglobins, as well as the level of C-reactive protein (CRP), was routinely measured on the collected peripheral blood through a blood analyzer .Erythrocyte sedimentation rate (ESR): ESR was measured by an automatic erythrocyte sedimentation rate analyzer .Serum calcium and adenosine deaminase (ADA): the levels of serum calcium and ADA were detected by a biochemical analyzer .Pulmonary function test (PFT): the pulmonary function of patients, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), total lung capacity (TLC), carbon monoxide diffusing capacity (DLCO), and partial pressure of blood oxygen (PaO2), was detected using a pulmonary function tester .Bronchoscopy: the percentages of lymphocytes and neutrophils in bronchoalveolar lavage fluid (BALF) were detected.All cases underwent chest computed tomography. The results showed 54 cases (77.14%) of symmetrical BHL, 5 cases (7.14%) of unilateral hilar lymphadenopathy, and 64 cases (91.43%) of mediastinal lymphadenopathy. There were 55 cases (78.57%) of pulmonary involvement, 37 cases (67.27%) of small nodules or patchy opacities which were predominantly distributed in the upper and middle lung zones, 18 cases (32.72%) of reticular opacities, and 9 cases (12.85%) of small amounts of pleural effusions.Biopsy specimens were obtained via EBUS-TBNA, transbronchial lung biopsy (TBLB), CT-guided percutaneous fine-needle aspiration, video-assisted thoracoscopic surgery, peripheral lymph node biopsy, skin biopsy, etc. Of the above various sample collection methods, EBUS-TBNA and/or TBLB was performed in 50 cases, skin biopsy or peripheral lymph node biopsy was performed in 13 cases, CT-guided percutaneous fine-needle aspiration was performed in 2 cases, and video-assisted thoracoscopic surgery was performed in 5 cases.t test and analysis of variance were used to compare the differences in variables between groups. Count data, represented as a constituent ratio, was compared by the chi-square test. Pearson's correlation analysis was used for correlation analysis between two groups. The diagnostic test of sACE in sarcoidosis was performed by receiver operating characteristic (ROC) curve analysis. Differences with P values < 0.05 were considered statistically significant.All data were analyzed by statistical software SPSS 21.0. The data were presented in the format of mean ± SD. Unpaired Among the 70 sarcoidosis cases, 56 cases (80.00%) were female. The mean age of the total sarcoidosis cases was 55.94 ± 11.83 years, with 52 cases (74.28%) presenting respiratory symptoms.P = 0.001). The percentages of lymphocytes and neutrophils in BALF of sarcoidosis patients were significantly higher than those of nonsarcoidosis patients (P < 0.001). Although 30 (42.85%) sarcoidosis patients presented with elevated ESR, there was no statistical difference in ESR level between sarcoidosis and nonsarcoidosis patients nor were there any significant differences in age and results of CBC and PFT between sarcoidosis and nonsarcoidosis patients. Forty-six sarcoidosis patients underwent tuberculin skin test (TST), returning 38 (82.61%) negative, 4 (8.70%) weak positive, and 2 (4.35%) positive results. Twenty cases exhibited abnormal PFT results, with 5 cases showing restrictive ventilatory defect, 14 cases showing obstructive ventilatory defect, and 1 case showing mixed ventilatory defect. The damage of PFT was mild in sarcoidosis patients.The mean value of sACE in sarcoidosis patients was 56.61 ± 30.80 U/L, which was significantly higher than that in nonsarcoidosis patients . Data are shown in Fifty-nine cases (57.1%) underwent bronchoscopy, and BALF was obtained from all of them. The percentage of lymphocytes in BALF of sarcoidosis patients was significantly higher than that of nonsarcoidosis patients , while there was no significant difference in age, gender, clinical manifestations, CBC, ESR, and PFT among them. Data are shown in The sACE level in patients with intrathoracic sarcoidosis was 47.05 ± 23.66 U/L, the sACE level in sarcoidosis patients involved both intrathoracic organs and peripheral lymph nodes was 56.47 ± 29.68 U/L, and the sACE level in sarcoidosis patients with multisystemic involvement was 64.94 ± 39.72 U/L. The level of sACE in sarcoidosis patients with peripheral superficial lymph nodes and multisystemic involvement was significantly higher than that in intrathoracic sarcoidosis patients (P < 0.05). The mean DLCO%pred was 86.24 ± 13.17% in stage I sarcoidosis patients, 77.45 ± 12.94% in stage II sarcoidosis patients, and 66.05 ± 17.93% in stage III sarcoidosis patients, with statistical significance (P < 0.05). As to the percentage of lymphocytes in BALF, there was no statistical difference between subgroups of sarcoidosis with different stages (P = 0.963). Data are shown in There was no statistical difference in age, gender, clinical manifestations, sACE, CBC, and ESR between sarcoidosis patients of different types of system involvement. As to PFT, the mean FEV1%pred was 99.67 ± 12.55% in stage I sarcoidosis patients, 81.43 ± 15.60% in stage II sarcoidosis patients, and 93.42 ± 20.49% in stage III sarcoidosis patients, with statistical significance  was 0.819. Thus, sACE ≥ 44.0 U/L may be an ideal cut-off value in sarcoidosis diagnosis. The ROC curve is shown in There was no correlation between sACE and ESR .Sarcoidosis is a multisystemic granulomatous disease with the common respiratory symptoms including cough, dyspnea, and chest pain, often accompanied by fatigue, malaise, fever, and weight loss . SarcoidOf the 70 sarcoidosis cases in this study, 52 cases (74.28%) presented with varying degrees of respiratory symptoms such as cough, expectoration, chest distress, and shortness of breath. Extrathoracic involvement can occur in some sarcoidosis patients, which mainly involves the skin, eye, liver, spleen, and cardiac system, presenting as fever, weight loss, and fatigue. In this study, the peak age of onset is middle-aged, with a predilection for women, which is consistent with the previous report . Over 90The final diagnosis of sarcoidosis is based on histopathology, so histopathology is strongly recommended in patients with suspected sarcoidosis. Peripheral lymph node biopsy or skin biopsy is a simple, safe, and reliable diagnostic approach. For patients without peripheral lymphadenopathy or skin involvement, EBUS-TBNA combined with TBLB is a relatively simple and safe diagnostic method with a high positive rate. In this survey, 50 cases underwent EBUS-TBNA and/or TBLB, and the histopathological diagnostic rate was 71.4%, which was similar to the positive rate of 88% reported internationally.The exact etiology and pathogenesis of sarcoidosis remain unknown. In the diagnosis and prognosis evaluation of sarcoidosis, the ideal marker to indicate diagnostic approach and disease activity monitoring has not yet been discovered . ElevateIn this study, the level of sACE in sarcoidosis patients was significantly higher than that in nonsarcoidosis patients with hilar and/or mediastinal lymphadenopathy. sACE can be an indicator for differential diagnosis of lymphatic involvement in nonsarcoidosis patients. It is reported that ESR is a useful marker of sarcoidosis activity . The levSarcoidosis can involve multiple systems with complex and varied clinical manifestations. Over 90% of sarcoidosis patients have pulmonary involvement. Although extrathoracic presentations as the initial symptoms of sarcoidosis are rare, accounting for 23% of sarcoidosis inpatients, they can be the main clinical manifestations and characteristics in some patients with sarcoidosis. According to a survey of 22 sarcoidosis cases whose initial symptoms were extrathoracic symptoms, 6 cases were identified as peripheral lymphadenopathy, 5 cases as skin involvement, 2 cases as ocular involvement, 3 cases as parotid gland sarcoidosis, 3 cases as arthritis, 1 case as cardiac sarcoidosis, 1 case as hepatic and splenic enlargement, and 1 case as neurologic sarcoidosis. Sarcoidosis has varying clinical manifestations and characteristics, which are related to race, staging, systemic involvement, and granulomas activity. The results of this study indicated that the sACE level was significantly higher in extrathoracic sarcoidosis. sACE levels reflect the varying degrees of granuloma, rather than pure pulmonary involvement, and are correlated with disease activity and extent. The level of sACE tends to be higher when sarcoidosis is active. Thus, sACE can indicate extrathoracic involvement in sarcoidosis.In this study, 44.0 U/L of sACE was defined as the optimal diagnostic cut-off for sarcoidosis diagnosis. We used 44.0 U/L as the diagnostic cut-off and histopathology as the golden diagnostic criterion to make a diagnosis in 84 cases. The results showed that although the sensitivity of sACE ≥ 44.0 U/L for sarcoidosis diagnosis was 61.4%, the specificity of 92.9% was high and ideal. According to data from Judson , the sensACE is an important diagnostic approach for sarcoidosis diagnosis. However, the normal range of sACE should be revised based on analysis of large sample data from multicenter investigations to improve the diagnostic efficiency of sarcoidosis. In addition, the high level of sACE in sarcoidosis patients with extrathoracic involvement suggests that sACE can be used as an important indicator for further screening and assessment of extrapulmonary involvement.


In the present study, a simple and low-cost strategy has been employed to fabricate nanoporous Mn2O3 with an increased surface area for an electrode/electrolyte interface that improved the conduction of Mn2O3 material. The crystal phase and morphology of the prepared material was investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). The prepared electrode materials were deposited on a nickel foam substrate to investigate the electrochemical properties. The galvanostatic charge/discharge (GCD), cyclic voltammetry (CV), and complex impedance studies confirmed excellent specific capacitance and capacitive behavior of the prepared material. The synthesized Mn2O3/graphene composites exhibited an excellent specific capacitance of 391 F/g at a scan rate of 5 mV/S. Moreover, a specific capacitance of 369 F/g was recorded at a current density of 0.5 A/g using the galvanostatic charge/discharge test. The high porosity of the materials provided a better electrolyte-electrode interface with a larger specific area, thus suggesting its suitability for energy storage applications.A simplified sol-gel method that can be scaled up for large-scale production was adopted for the preparation of manganese oxide nanocrystals. Prepared Mn Over the past few decades, energy storage strategies are one of the key challenges owing to the progressive exhaustion of fossil fuels and a fast energy depletion rate . Renewab2O3 composite electrode on Ni foam, while in the present study effective and simple techniques are used to get the valuable electrochemical results . Mn2O3 is an inexpansive, environmental friendly, naturally abundant material  and the microstructural features by scanning electron microscopy (SEM). The elemental study was performed by an energy-dispersive X-ray spectroscopy (EDX). The main focus of the present study was to investigate the electrochemical performance of prepared composite materials. In the present study, the electrochemical performance demonstrates that Mn2O3/graphene nanocompsites have great potential with a simple and low-cost method as compared to report previous.In the recent past, lot of efforts have been made to synthesize a composite material to exploit the properties of both carbonaceous (high conductivity) and transition metal oxides (TMOs) (high specific capacitance) such as a manganese oxide composite with carbon nanofoams , carbon material . The commaterial . Herein,2O3 nanoparticles by dissolving 25 gm of manganese nitrate (Mn(NO3)2.4H2O) in 100 ml of ethylene glycol. The amount of the solvent was adjusted such that manganese nitrate was completely dissolved. The solution was further heated at 80°C under continuous stirring until a thick gel was formed. The gel burnt slowly into a fine powder by increasing temperature to 100°C. The resultant powder was sintered at 700°C in an electric furnace for 4 hours.The sol-gel method was used  to synth2O3/graphene with the ratio  were prepared by mixing appropriate amounts of the composition with a mortar and pestle for 30 min. Then the mixture was dispersed in deionized water and sonicated for 30 min hour. Afterward, the mixture was poured into an electric motor blender and was blended for 30 min. While blending, nanoporous Mn2O3 micro-particles having higher density than graphite acted as high-energy projectiles hitting graphite clusters and exfoliated them to graphene, thus improving uniformity and mixing of the composites. Afterward, a microwave oven has been employed to dry the obtained composite materials for 1 hour.The composites of Mn2 × 1 cm2) was used as a substrate. The deionized water was added to the mixture of composite material and PVA (10%) to make a thick slurry. This slurry of the composite material was then transferred into a glass tube and sonicated for 15 min. The substrate was inserted into the slurry and sonicated for 10 min such that the pores of the Ni foam (The Ni foam with an area of about (1 cm Ni foam  uniformlα) having a wavelength of 1.54 angstrom as an X-ray source.The materials were explored for structural properties by employing the XRD technique. The crystal structure of the synthesized materials was investigated by employing an X-ray powder diffraction technique  with Cu  the plane of the cubic structure of Mn2O3 by using the Deby–Scherer equation, which was found to be 22.67 nm , atom coordinates , cell geometrical parameters  and , occupation (occ), thermal parameters (Bs), and FWHM parameters . The agreement between the experimental and approximated profiles was checked by the discrepancy factors which comprise the expected R-factor (Rexp), the Bragg R-factor, the weighted profile R-factor (RWP), and goodness of fit (χ2). The XRD Rietveld refinement revealed a cubic unit cell with a space group symmetry of Ia-3 space and computed various structural parameters of the crystal structure for Mn2O3 particles. The summary of the refined results are enlisted in the table.The material was further investigated for the crystalline structure and a quantitative analysis, and the XRD profile of Mn2O3/graphene composite. Here, the black symbol (star) marks the Bragg reflections of the Mn2O3 single phase, while the high intensity diffraction peak appearing at 2θ value of 44.57° represented by green symbol (triangle) indicates the Bragg reflections arising from graphene. Thus, the XRD profile confirms the presence of both phases and assures the successful formation of Mn2O3/graphene composite.2O3 has been examined by an energy-dispersive x-ray (EDX) technique, as shown in 2O3 and discard the presence of other elements; this assures the phase purity of the material and hence these results are consistent with the XRD data discussed earlier  MIRA3 TESCAN, as shown in 2O3 single phase. From the figure, it can be observed that surface morphology of Mn2O3 exhibits a nanoporous structure with agglomerated crystallites. The agglomeration may occur due to sintering of the material at higher temperature of about 700°C and also of magnetic nature of its nanoparticles  as a reference electrode, platinum (Pt) is used as a counter electrode, and Mn2O3/graphene as a working electrode in 1 M K2SO4 as electrolyte.The galvanostatic charge discharge and cyclic moltamogram measurements in a three electrode setup have been used to study electrochemical performance of Mn2O3 nanoparticles in aqueous electrolyte indicative of pseudocapacitive behavior. The pseudo capacitance may arise from an Mn+3/Mn+2 couple. The below-mentioned equation was used to determine the specific capacitance of the cell  give high specific capacitance. Specific capacitances of all three composites were estimated using The cyclic voltammetric study performed at 5, 10, 20, 50, and 100 mV/s scan rates, respectively, for all three composites, as shown in the cell :Ccell=Q2At a higher scan rate, all the charges accumulate at the surface of the electrode material. But at the lower scan rate, ions have ample time for their diffusion in the bulk part of the material to accumulate larger amount of charges and hence results in higher specific capacitance , as show2SO4 electrolyte, as depicted in The GCD analysis for all three given samples A, B, and C  at different current densities in 1 M solution of KA sinusoidal potential is applied to measure the current that passes through an electrochemical cell and an AC voltage is used to measure the electrochemical impedance which depicted the AC current along with excitation potential including its harmonics . The pse|Z|. The data for EIS can be demonstrated by equivalent circuit models  exponent m, pore resistance Rpor, corrosion “double layer” capacitance Ccor, a (CPE) exponent n, and corrosion resistance Rcor of the Mn2O3/graphene composite electrode material  and do not behave ideally  of the synthesized material. The value of R ideally . The imp the CPE .2O3/graphene composite is shown in x-axis, while the phase-shift and absolute values of the impedance (|Z| = Z0) are taken along the y-axis. In the abovementioned figure, the Bode plot of Mn2O3/graphene composite is sketched using the logarithmic scale. By changing the frequency of the as-prepared composite, the magnitude and the phase angle is obtained. The phase angle tells about the behavior of the supercapacitor.The Bode plot of MnThe pseudocapacitve behavior can be clearly evident from the charge discharge cycles which have increased the specific capacitance, as shown in 2O3/graphene composite was synthesized with a simple, low-cost, environmental friendly facile method. Herein, the sol-gel–derived Mn2O3 resulted in a nanoporous structure of prepared materials. The high porosity of the materials provides a better electrolyte-electrode interface with a larger specific area that was desirable for energy storage applications. Composites of Mn2O3/graphene were prepared with sonication plus electric motor blending. The method used is simple and cost-effective that can be scaled-up for industrial scale production. Mixing of composites by sonication and mechanical blending resulted in exfoliation of graphene and uniform mixing of composite electrode materials. The XRD pattern confirmed a cubic structure of Mn2O3 having a crystallite size of about 22.7 nm. The surface morphology of Mn2O3 investigated by SEM exhibited nanoporous microstructures. SEM micrographs of the composite revealed the uniform mixing of Mn2O3 with exfoliated graphene sheets. Furthermore, the electrochemical data of different mass ratios of Mn2O3/graphene composites obtained from GCD and CV showed an improved capacitance in the applied potential window. This report provides an effective and simple route to synthesize Mn2O3/graphene composites with an enhanced electrochemical performance for supercapacitor applications. Sample with an Mn2O3/graphene ratio of 1:3 has highest specific capacitance of up to 391 Fg-1 at a scan rate of 5 mV/s due to a large surface area and high conductivity provided by increased amount of graphene. This research work provides an effective and simple way to prepare manganese oxide Mn2O3/graphene composites with high electrochemical performance for supercapacitors. Samples of Mn2O3/graphene with ratios 1:1, 1:2, and 1:3 have specific capacitance of 271, 321, and 391 Fg-1, respectively, at a scan rate of 5 mV/s. The capacitance of composite exhibited an increasing trend with the increasing graphene concentration. These results lead to the conclusion that composite is useful electrode material for super capacitor applications.An Mn


Over the last decades, severe haze pollution constitutes a major source of far-reaching environmental and human health problems. The formation, accumulation and diffusion of pollution particles occurs under complex temporal scales and expands throughout a wide spatial coverage. Seeking to understand the transport patterns of haze pollutants in China, we review a proposed framework of time-evolving directed and weighted air quality correlation networks. In this work, we evaluate monitoring stations’ time-series data from China and California, to test the sensitivity of the framework to region size, climate and pollution magnitude across multiple years (2014–2020). We learn that the use of hourly  The accelerated industrialization and urbanization of many economically developing countries has led to major air pollution with severe impacts both for human health and the environment  in the segment connecting the Bay Area with Los Angeles.As for the spatial distribution in China, Fig. T according to:i is denoted by series i to j for Following an analysis framework proposed and applied for the study of environmental complex systems , and computed as the average of absolute values of correlations from the permuted data. That way, correlations appearing less in the randomized version do not generate links.As in our predecessor studies, the weighted adjacency matrix of the correlation network of week The strength of the correlations can also be quantified by standardizing the correlations i and j defined asTo quantify the influence of a node to its surroundings, we use the weighted directional degree, as introduced in Zhang et al. . For thei and j respectively.t we are evaluating, the communities generated are very stable. Variations in number of communities are minor and only express a merge or split of communities with not significant jumps of nodes between communities. For each network, the algorithm is being run 100 times. For the minority of nodes that may switch communities across runs, we assign them to the community they appear in the most.Community detection algorithms aim to decompose a network into sets of sub-units comprising of highly inter-connected nodes  networks leads to evolving communities with time. To track the changes in structure, we treat our networks as a time-series of static networks, called timeframes with weekly resolution, according to the method proposed by Greene et al. . We aim D we deploy the heuristic threshold-based method introduced by Greene et al. Greene et al.  to account for the seasonal dependence of -3. Over the next two days, -3. The increases were abrupt, causing sharp peaks in the time-series raising the concentrations to four times the average up until that moment during the week. In our example, the majority of generated correlations are positive. Figure In Fig. entclass1pt{minimaNetworks are formulated under both methods as defined in the Data and Theoretical Background section. For the method of the maximal value of the cross-correlation function, all links receive absolute values above the critical correlation threshold  formulates less densely connected networks. The Z-scores, which are computed through standardization of the correlation function, share the same shape PDF }PC Fig. e, but whBased in our analysis with hourly data at a weekly scale and focusing in haze events, we conclude the Z-score approach overcomes the artificial correlations due to persistence and auto-correlations the time-series. These phenomena are frequent in environmental and climate related variables  wind flows were strong northern over the California coast while Southern California’s were weak and of varying directions  of 2020 versus networks from the same dates in 2014 to 2019. This comparison helps us draw conclusions under similar meteorological conditions (same dates across different years) but with significantly reduced emissions from human mobility because the lockdown. Figure To determine regions with systematic pollution transport behavior, the Louvain algorithm of network community detection was applied to identify partitions in the dynamic AQ networks formulated under the Z-score method. We apply the method in China where more monitoring stations are available and pollution haze events are attributed to less unpredictable and variable events such as the California wildfires. This study emphasizes on long-lived and persistent dynamic communities that appear for several consecutive weeks and persist across our years of evaluation. With The southeastern community (blue) appears to be the least persistent of the four according to Fig. mentclass2pt{minimWe identify the core nodes of the four dynamic communities as the nodes appearing in more than half of the timestamps (weeks) the DC appears. That translates to 21, 23, 17 and 18 nodes for the red, green, blue and yellow dynamic communities respectively. As shown in Fig. Our work has shown that the development of directed and weighted air pollution correlation networks exploiting hourly We deem that the Z-score method, based on standardization of the correlation function, is more insightful than the maximal value of the correlation function when it comes to analyzing haze events with sharp peaks. It overcomes the artificial correlations due to persistence and auto-correlations within the time-series records. As shown in Fig. We extend the Z-score network analysis framework via the Louvain method of community detection in China. Results demonstrated distinct communities presenting consistent air pollution transport patterns and high interconnections between their cities across all years of evaluation. In more detail, four communities prevail as the most persistent grouping the provinces of Shangha–Jiangsu, Shandong, Heibei–Beijing–Tianjin–Liaoning, and Hunan–Jiangxi–Guangdong. The four dynamic communities align geographically with the BTH, Yangtze River Delta, and the Pearl River Delta which correspond to the regions in China with the highest concentrated populations attracted from the river basins and constitute the nuclei of the highest industrial output. Interestingly, identifying the core nodes of the four communities, we showed that they are sufficient to reproduce the key temporal and spatial patterns of the analysis. Apart from significantly reducing the complexity of the original networks, this offers potential as a pre-processing method for AQ forecasting and prediction of extreme pollution events as well as informing the re-positioning of stations to monitor areas with no records. Overall, the network partitioning allows to disentangle spatial patterns, identifying regions where pollution transport is more persistent.


Chile, Argentina, Costa Rica, Puerto Rico, Colombia, and Brazil had overall rates between 13 and 17 per 100,000 during the same period.7 Similarly, Asian countries such as Thailand and Korea have reported an increase in mortality rates from 50% to 260%, respectively.8 In the same direction, Center et al4 have reported a rapid increase in mortality in most Central and Easter European countries.On the other hand, many developing countries in Latin America such as Colombia, Costa Rico, and Ecuador have experienced increasing PCa trends from 1993 to 2002, and countries such as Brazil, Colombia, Cuba, and Ecuador have reported an increase in mortality rates.9 have reported that advanced-stage rates in East Africa have been much higher than those of African Americans in recent years. As an example, Osegbe10 reported that 64% of patients with new PCa in a Nigerian hospital died within 2 years of diagnosis. It has been estimated that 57,048 deaths associated with PCa will occur in Africa by 2030. This represents a 104% increase in the number of PCa deaths in Africa over the next 20 years.11Although the cancer-specific mortality has been reported to be the lowest in Asia and Northern Africa, Chu et al12A total of 28,000 deaths of men of all ethnicities in Africa because of PCa as reported were more than four times the 6,500 that occurred among Caribbean men of all ethnicities and exceeded deaths from any other cancer in Africa.13There are multiple reasons aside from variation in tumor biology for the increased mortality rates in developing countries, which include lack of a screening program, diagnosis at an advanced stage, limited access to local and systemic treatments, most affected being urban poor or from rural and remote populations having poor or no healthcare coverage, lack of affordable transportation to health centers, limited number of critical therapeutical tools such as radiation therapy, missing specifically trained healthcare staff including physicians with not a full training in oncology, and lack of information and guidelines. Many guidelines have addressed the gold standard in the diagnosis and management of PCa such as the National Comprehensive Cancer Network guidelines, but in general they do not provide specific, detailed, and adapted information and guidance for low-resources areas.14The first Global Prostate Cancer Consensus Conference for Developing Countries (PCCCDC) was organized around state-of-the-art lectures and presentations and discussed evidence relevant to 12 key topics and subtopics related to the management of PCa in general and in limited-resource regions . Four polling sessions were scheduled during the 2-day conference for panelists to respond to questions regarding these topics. Only physicians who participated in all four sessions are included in the final consensus results. Several of the questions were based on the questions from the Advanced Prostate Cancer Consensus Conference (APCCC) 2017, the conference that stimulated and inspired the PCCCDC.The full panel for this consensus paper consisted of 99 multidisciplinary cancer physicians including urologists, medical oncologists, radiation oncologists, radiologists, and pathologists from developing countries in Latin America, Africa, Middle East, Asia, and Eastern Europe. The panel members were selected on the basis of recent work and their willingness to be present at the first PCCCDC. The draft of recommendations and clinical questions were selected previously by a committee composed of specialists in the fields. The committee of radiologists was led by Douglas Racy, MD; the committee of radiotherapy was led by Robson Ferrigno, MD; the committee of urology was led by Arie Carneiro, MD, Murilo Luz, MD, and Gustavo Guimarães, MD; the committee of oncology was led by Fernando Cotait Maluf, MD, Felipe Moraes, MD, and Andrey Soares, MD.14 The conference included presentations and debates from participants who reviewed evidence relevant to the above questions. On the last day of the conference, all questions were presented with options for answers in a multiple-choice format. The questions were voted on publicly but anonymously. In some cases, discussions and revoting occurred. Each question had five to seven answer options including two nonanswers . Each question was deemed consensus if 75% or more of the full panel selected a particular answer. The two nonanswers were provided for quality control. Unless stated otherwise, it is assumed that for the specific recommendation , therapies are approved and available, no treatment contraindications exist, and no clinical trial is currently ongoing. If consensus is not achieved, then the Steering Committee may opt to leave a clinical question unanswered and state, “Consensus could not be achieved.” All the questions can be accessed in the Data Supplement. For the questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier access. In addition, recommendations are for nonfrail patients and for patients with prostate adenocarcinoma (unless stated otherwise). Their answers are annotated and discussed in the following manuscripts that address screening, diagnosis, and staging tools, and treatments for the topics are stated in Table The consensus was developed on the basis of a modified Delphi approach Fig . In a moThe panel for this consensus paper consisted of 99 multidisciplinary cancer physicians including urologic surgeons, medical oncologists, radiation oncologists, radiologists, and pathologists from developing countries in Latin America, Africa, Middle East, Asia, and Eastern Europe. The selection of panel members was based on special expertise in PCa, recent work in this field, and their willingness to attend the first PCCCDC. All the participants and medical specialties are included in the Data Supplement.14 Following each question, there were five to seven answers options including the option to abstain and/or to identify that they felt unqualified to answer. These options allowed for physicians to opt out of questions that they may not contend with in their specific specialty. Questions were designed to include recommendations of therapies or treatments that are approved and available, and no treatment contraindications exist, unless otherwise stated in the question. An answer was deemed to have reached consensus if 75% or more of the full panel selected a particular answer. For the questions referring to an area of limited resources, the clinicians were instructed to consider both cost-effectiveness and access.The questionnaire was developed by a panel of seven experts to provide relevant real-world physician recommendations for nonfrail patients (as defined by the Eastern Cooperative Oncology Group performance status 0-2) and for patients with prostate adenocarcinoma (unless otherwise stated). A total of 321 questions were constructed to investigate (1) screening, (2) diagnosis, (3) staging tools, (4) treatment, and (5) follow-up of PCa and the impact of limited resources on those treatment recommendations by panelists. For some topic, the questions were based on the APCCC 2017.The series includes seven articles compiling all the questions applied on the PDCCCD. The main objective of each article will be discussing the question raised and evaluating the voting panel and literature discussion related to the questions. The first article includes questions of the consensus on screening, diagnosis, and staging tools in PCa. Benefits on screening and early detection of PCa and limitations of screening diagnostic tools in countries of limited resources will be addressed. The second and third articles will include the consensus statement on treatment of localized PCa of low, intermediate, and high risk. In these articles, interventions for localized disease including active surveillance will be discussed, considering life expectancy and disease risk. The fourth article considers biochemical recurrence in castration-sensitive PCa. Challenges in the treatment of this disease rely on preventing or delaying the onset of metastatic disease; morbidity and mortality will be discussed in the article. The fifth manuscript will include questions on nonmetastatic castration resistance PCa, importance of PSA doubling time, and risk assessment. The sixth article will include questions about metastatic castration-sensitive prostate cancer, and the last article will include issues of metastatic castration-resistant prostate cancer. Discussions about staging, sequencing strategies, and limitations of access in areas of limited resources will be dissected.To provide valuable information for physicians and healthcare professionals who work in areas with limited resources, we sought to provide a global consensus including screening, diagnosis, staging tools, treatment, and follow-up for various stages of PCa for developing countries. The information provided in the consensus posing different scenarios will help to choose, when the gold standard options are not available, the best option possible considering a resource-limited scenario. We hope that the series will help physicians who work treating patients with prostate cancer in areas of limited resources to establish the best possible standard of care for the patients in these countries and help in guiding and educating responsible groups in these countries of the limitations faced by these professionals in the treatment of PCa.