IntroductionWhile Google is frequently used to access internet-based health resources, the quality of online health information remains variable. Our purpose was to assess suggested resources identified through Google search features for common symptoms related to carpal tunnel syndrome (CTS).MethodsTwo searches were performed. The first, labeled "symptom-related," included the terms "hand numbness," "hand tingling," and "hand falling asleep." The second, labeled "CTS-specific," included "carpal tunnel syndrome," "carpal tunnel surgery," and "carpal tunnel release." A novel feature of Google’s search engine is to display similar searches made by other users ("People Also Ask" snippet). For each search, the first 100 results snippets and the associated website links were recorded. A list of unique questions was compiled and classified into 1 of 3 categories using the Rothwell classification: fact, policy, or value. Questions were also classified based on the diagnoses suggested by the query. Website authorship was determined, and the corresponding links were categorized by two independent reviewers.ResultsThe "symptom-related" searches yielded 175 unique questions and 130 unique website links, and the "CTS-specific" searches yielded a total of 243 questions and 179 unique links. For "symptom-related" searches, 65% of questions suggested a diagnosis, with CTS being suggested as a diagnosis for only 3% of questions. In contrast, CTS was suggested by 92% of questions in "CTS-specific" searches. In both searches, nearly 75% of questions were classified as "facts." Commercial websites were the most common in both searches.ConclusionGoogle searches for common symptoms of median nerve compression rarely yield information related to CTS. The landscape of how patients obtain information regarding medical conditions and treatments has changed rapidly in the 21st century . ApproxiCarpal tunnel syndrome (CTS) is the most common compressive neuropathy of the upper extremity, affecting one to three patients per 1,000 per year . Costs aThe purpose of this investigation was to quantify and assess suggested resources identified through Google search features for common symptoms related to CTS as well as for direct searches regarding CTS and related surgery. In addition, we aimed to characterize the suggested resources provided by Google’s "People Also Ask" snippet. We hypothesized that suggested information found using symptom-related search terms would be related to CTS and would be predominantly produced by academic centers.www.google.com) that was clean-installed with the browser history removed to eliminate bias from Google’s personalized search algorithm. The first search was performed in September 2021, and the second search was performed in December 2022. For each search, the first 100 results of the "People Also Ask" snippet and the associated website links were recorded. A list of unique questions was compiled. Each question was categorized, according to Rothwell’s classification, into fact (is the given question true?) or policy (will a course of action solve a specific problem?) or value  [Two groups of searches were performed. The first, labeled "symptom-related," included the terms "hand numbness," "hand tingling," and "hand falling asleep." The second, labeled "CTS-specific," included "carpal tunnel syndrome," "carpal tunnel surgery," and "carpal tunnel release." Each term was individually queried into a Google Web Search (or bad?) .Questions populated by the "People Also Ask" snippet were classified based on any diagnosis suggested by the question, post hoc. These categories included cardiovascular, psychological, diabetes, nutrition, hydration, multiple sclerosis, nerve injury/damage, carpal tunnel syndrome, COVID-19, and none for the searches related to symptoms of carpal tunnel. Similar to previous studies ,11, eachThe questions and the corresponding links were categorized by two independent reviewers. Interobserver reliability was calculated using Cohen’s kappa coefficient. Discrepancies were resolved via consensus discussion with the senior author, where the category was discussed amongst all parties and the final decision was made by consensus regarding the definitive category. When discussing agreement levels for Cohen’s kappa coefficient, the following guidelines were utilized: slight (0.01-0.20), fair (0.21-0.40), moderate (0.41-0.60), substantial (0.61-0.81), and near perfect (>0.81) ,14.The "symptom-related" searches yielded a total of 230 unique questions and 130 unique website links for review. Fifty-five (24%) questions were deemed irrelevant and excluded, leaving 175 questions for evaluation. Irrelevant questions often related to common suggested diagnoses but did not allude to any of the queried symptoms. Cohen’s kappa coefficient was 0.954 for question classification and 1.000 for website classification.The "CTS-specific" searches yielded a total of 243 unique questions and 179 unique links for review. No questions were deemed irrelevant. Cohen’s kappa coefficient is 0.815 for question classification and 0.844 for website classification.For "symptom-related" searches, a diagnosis was suggested in 65% 120/175) of questions  of questions  of questions were classified as fact questions  of questions were classified as fact questions. Value questions represented 14.4% (n=35) of search questions, and policy questions represented 13.17% (n=32). The most common website categories were commercial , followed by medical practice  and academic .Contrary to our hypothesis, search terms representing the classic symptoms of CTS do not commonly yield resources pertaining to CTS. While nearly two-thirds of FAQs alluded to a diagnosis, less than 5% were related to CTS. Other common causes of these symptoms within orthopedics, such as radiculopathy or other compressive peripheral neuropathies, were not represented at all. The more commonly recommended diagnoses from this study, such as nutritional deficiencies, dehydration, and diabetes, rarely present with hand numbness -17. MostFor "symptom-related" searches, over half of all recommended questions were associated with a commercial link. Similarly, commercial websites were the most common category for "CTS-specific" searches. These findings are in contrast to previous studies on Google’s "People Also Ask" snippet ,11. SudaThese data highlight the limitations of patient-driven searches for online health information. The issue remains that resources from academic centers and professional societies are not prioritized by Google’s search engine, as evidenced by two different search queries. Patients searching online highly value convenience when selecting websites to review . TherefoSeveral limitations must be considered when interpreting our results. First, while we selected our "symptom-related" search terms based on common symptoms of CTS, our terms may not be representative of all common search terms used by patients. For example, we used the term "hand numbness" but not "why are my hands numb." Also, while Google is the most common search engine , our resGoogle searches for common symptoms of median nerve compression rarely yield information related to CTS. Information produced by academic institutions and professional societies is infrequently accessed via these searches, and the suggested information has a strong commercial influence. Suggested FAQs by Google may not be a reliable source for health information.


The previous epidemiological and experimental evidence has implied the linkage between chronic inflammation to idiopathic pulmonary fibrosis (IPF). However, it was still unclear whether there were casual associations between circulating inflammatory cytokines and IPF development. The objective of present study was to examine whether altered genetically predicted concentration of circulating cytokines were associated with IPF development using a two-sample Mendelian randomization (MR) analysis.The causal effects of 23 circulating inflammatory cytokines were evaluated on IPF using MR analysis. The primary approach of MR analysis was the inverse variance-weighted (IVW) method. The sensitivity analyses were conducted by simple median, weighted median, penalized weighted median and MR-Egger regression methods.The present MR study found suggestive evidence that a higher circulating IL-14 level was associated with an increased risk of IPF . The sensitivity analysis yielded directionally similar results for IL-14. There was no significant association found between other circulating inflammatory cytokines and IPF.The high level of IL14 predicted by genes had a casual relationship with the increased risk of IPF. This finding provided epidemiological evidence for drug therapy targeting inflammatory factors in the prevention and treatment of IPF. It’s warranted further exploration to validate the clinical significance of IL14 associated with developmental risk of IPF.The online version contains supplementary material available at 10.1186/s12890-023-02658-3. Idiopathic pulmonary fibrosis (IPF) is a prototype of chronic, progressive, and fibrotic lung disease with replacement of altered extracellular matrix and destroy of alveolar architecture, leading to decreased lung compliance, disrupted gas exchange, and ultimately respiratory failure and death . AlthougMendelian randomization (MR) is an observational study design that seeks to understand causal relationships between an exposure  and an outcome  by using genetic variants as instrumental variables, which has been widely applied to mitigate certain significant drawbacks encountered by conventional observational studies . Specifihttps://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST90018120/.We employed a two-sample MR analysis model in order to assess the causal impact of circulating inflammatory cytokines on IPF, as depicted in Fig. https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST90018120/ [We employed a rigorous approach to identify SNPs that exhibit a significant association with circulating inflammatory cytokines. These identified SNPs were subsequently utilized as instrumental variables (IVs) in our analysis. The selection criteria for these IVs included a stringent significance threshold (P < 5 × 10 − 6), as well as specific considerations pertaining to linkage disequilibrium (LD), whereby the LD measure (r2) was required to be below 0.001 and the LD distance to exceed 10,000 kb. Subsequently, we endeavored to locate information regarding the aforementioned IV SNPs within the IPF dataset sourced from large-scale GWASs. Specifically, this IPF dataset was acquired from the prominent GWAS conducted by Duckworth, as identified by the unique identifier (id: ebi-a-GCST90018120). Readers looking to access the detailed data for IPF can refer to the following resource: 0018120/ . The stu0018120/ .In this study, a comprehensive array of seven MR analysis methods were employed. These methods encompassed the inverse-variance weighted (IVW) technique, both in the fixed-effect and random-effect frameworks, alongside the simple median, weighted median, penalized weighted median, MR Egger, and MR Egger (bootstrap) approaches. The IVW method, serving as the primary analytical tool, was utilized due to its ability to yield reliable estimates of causal effects, even in the presence of heterogeneity. To further ensure robustness and explore potential sources of bias, two additional methods, namely the weighted median estimator and MR-Egger, were implemented for sensitivity analyses. The weighted median estimator was particularly proficient in furnishing dependable causal assessments when a majority of the instrumental variables adhered to MR assumptions. On the other hand, the MR-Egger estimate remained unbiased under the proviso that the genetic instrument exhibited no dependency on pleiotropic effects. Moreover, in order to comprehensively evaluate the presence of pleiotropic effects and heterogeneity among individual SNPs, we employed the IVW method in conjunction with MR Egger intercept and Cochran’s Q statistics. The absence of pleiotropic effects was determined if the intercept did not significantly deviate from 0 (p > 0.05). Heterogeneity, on the other hand, was assessed based on the value of Cochrane’s Q statistic. When the p-value of this statistic was less than 0.05, the IVW method with a multiplicative random-effects model was selected as the primary outcome. Conversely, if the p-value was greater than or equal to 0.05, the IVW method with a fixed-effects model was considered the primary outcome. To further account for potential pleiotropy and derive a causal effect assessment while addressing the issue of directional horizontal pleiotropy, MR-Egger regression was also performed in this study. Furthermore, a leave-one-out analysis was conducted to assess the robustness of the MR analysis results by examining the influence of individual outlier SNPs. In line with a previous study, a causal relationship was deemed significant if three conditions were met: (1) the p-value of the IVW method was less than 0.05, (2) the estimates from the IVW, MR-Egger, and weighted median methods were consistent in direction, and (3) the p-value of the MR-Egger intercept test was greater than 0.05. All statistical analyses were undertaken using the “TwoSampleMR” package in R version 3.4.1 , and a two-tailed p-value of less than 0.05 was considered statistically significant.We included 555 SNPs significantly related to the circulating inflammatory cytokines variation as IVs for circulating inflammatory cytokines-IPF causal estimations. We used a 2-sample MR model to evaluate the causal effect of circulating inflammatory cytokines on IPF Fig. . The genGenetically predicted higher plasma CRP levels showed a suggestive inverse association with IPF using IVW method   were performed as the complement to IVW, confirming the robustness of the IVW analysis results. The MR analysis by MR Egger and IVW showed that IL2 was not significantly associated with risk of IPF  Table ; Fig. 3.The MR analysis by IVW models and other analytic methods  showed that MCP1 was not significantly associated with development risk of IPF (P > 0.05) Table ; Fig. 4.The present study carried out a series of sensitivity analyses to evaluate the potential horizontal pleiotropy. The results of MR-Egger Intercept-test indicated that there was not significantly impact caused by horizontal pleiotropy (P > 0.05). The results of the leave-one-out sensitivity analysis suggested that the association between inflammatory cytokines and IPF was not substantially driven by any individual SNP .The present study performed a two-sample MR analysis to explore genetic evidence to support causal relationships of circulating inflammatory cytokines with the risk of IPF. The current MR study demonstrated that genetically proxied higher circulating IL14 level was causally associated with an increased risk of IPF, whereas no significant associations were found between genetically higher exposures of other circulating inflammatory cytokines levels  and IPF. These findings provided epidemiological evidence for drug therapy targeting inflammatory factors in the prevention and treatment of IPF.IPF is characterized as a profoundly debilitating interstitial lung disease, with a rapid deterioration in lung function and a mortality rate of 50% within 3–5 years following diagnosis , 24. WhiInflammation, recognized as a critical component in numerous autoimmune disorders, is widely implicated in various significant pathogenic processes of IPF. These include epithelial-mesenchymal transition, epithelial cell apoptosis, impaired fibrinolytic system, and myofibroblast accumulation, which are considered pivotal in the pathophysiology of IPF –30. The In our study, we successfully established a causal link between serum IL14 levels and an elevated risk of developing IPF. However, it is important to note that the incremental risk associated with IL14 levels was not substantial, and its clinical significance may be limited. As for the relationship between other inflammatory cytokines and IPF, no causal link has been established thus far. Therefore, based on the current body of research, it is our belief that the pathogenesis of IPF is not triggered by fluctuations in serum inflammatory cytokine levels. Instead, these fluctuations may be a consequence of the progression of IPF. Moreover, our study yielded robust null results for circulating inflammatory cytokines , indicating that prolonged exposure to elevated levels of these circulating inflammatory cytokines does not increase the risk of IPF. Presently, the blocking of inflammatory cytokines appears to hold promising potential as a therapeutic approach in IPF drug therapy. A phase 2, randomized, double-blind, placebo-controlled trial conducted by Maher et al. in 2021 has recruited about 500 patients with IPF to evaluate the efficacy and safety of lebrikizumab , alone or with background pirfenidone therapy . Interes− 6), which may introduce bias when weak IVs are included. Fourthly, the scope of our study was limited to individuals of European descent, thereby limiting the generalizability of our findings to individuals of other ancestral backgrounds. Consequently, the present study does not provide support for a causal relationship between levels of 27 inflammatory cytokines and IPF. Considering the restricted dataset of inflammatory factors included in our analysis, alternative datasets examining inflammatory factors are needed to validate our findings. Therefore, we anticipate that future studies incorporating updated GWAS data on inflammatory factors will serve to further validate the results of our investigation.Several limitations warrant consideration in our study. Firstly, although no causal association was observed, it is possible that the effect size is too small to be detected comprehensively, although this cannot be definitively ruled out. Secondly, the lack of available data pertaining to the pathological classification of IPF hindered our ability to conduct further analyses specifically examining IPF subtypes. As such, further investigation into IPF subtype analysis is necessary to elucidate the potential correlation between levels of circulating inflammatory cytokines and IPF across different subtypes. Thirdly, the identification of IVs was conducted using a relatively stringent threshold (p < 5 × 10The high level of IL14 predicted by genes had a casual relationship with the increased risk of IPF. No significant associations were found between genetically higher exposures of other circulating inflammatory cytokines levels and IPF. These findings provided epidemiological evidence for drug therapy targeting inflammatory factors in the prevention and treatment of IPF. It’s still warranted further exploration to validate the clinical significance of IL14 associated with developmental risk of IPF.Below is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2Supplementary Material 3Supplementary Material 4


Venetoclax is a small molecule inhibitor of BCL-2 used in the treatment of acute myelogenous leukemia and chronic lymphocytic leukemia. Recent post-marketing studies on venetoclax suggested that it may predispose to opportunistic infections (OIs). We sought to systematically review the randomized controlled trial (RCT) evidence on venetoclax to assess whether it predisposes patients to infectious adverse events (IAEs) and neutropenia.i.e., a regimen with additional anti-cancer agents) or placebo controls in patients with hematologic malignancies, irrespective of treatment line. Data on IAEs and neutropenia were pooled by Bayesian meta-analysis and we computed the probability of any increased risk in infectious or neutropenic complications (Risk Ratio [RR] >1). Subgroup analyses were conducted based on treatment line, use of an inactive comparator, malignancy type, and prophylaxis strategy. Additionally, we pooled the incidence rates of fatal OIs between venetoclax and comparator arms and compared them by univariate meta-regression.We systematically reviewed the RCTs comparing venetoclax therapy to active . The probabilities of venetoclax increasing the risk of grade 3-5 and fatal IAEs were 86.6%  and 81.1% , respectively. There was a 97.2% likelihood that venetoclax increased the risk of grade 3-5 neutropenia . Venetoclax treatment did not increase the incidence of fatal OIs (P=0.55).Our results suggest that venetoclax likely increases the risk of high-grade neutropenia and IAEs overall, but not fatal OIs. However, our analyses did not identify any specific IAEs that would benefit from routine anti-infective prophylaxis or pre-emptive testing.Michael Sebag, MD, PhD, Amgen: Advisor/Consultant|BMS: Advisor/Consultant|Focus Therapeutics: Advisor/Consultant|Gilead: Advisor/Consultant|Janssen: Advisor/Consultant|Novartis: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi: Advisor/Consultant Matthew Cheng, MD, Amplyx Pharmaceuticals: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Honoraria|Cidara Therapeutics: Grant/Research Support|GEn1E lifesciences: Advisor/Consultant|GEn1E lifesciences: Stocks/Bonds|Kanvas Biosciences, Inc.: Board Member|Kanvas Biosciences, Inc.: Pending patents|Kanvas Biosciences, Inc.: Ownership Interest|Merck: Honoraria|nomic bio: Advisor/Consultant|nomic bio: Stocks/Bonds|Pfizer: Honoraria|Scynexis Inc.: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Honoraria


There is a constant need to maintain the quality of consumed food. In retrospect to the recent pandemic and other food-related problems, scientists have focused on the numbers of microorganisms that are present in different food items. As a result of changes in certain environmental factors such as temperature and humidity, there is a constant risk for the growth of harmful microorganisms, such as bacteria and fungi, in consumed food. This questions the edibility of the food items, and constant monitoring to avoid food poisoning-related diseases is required. Among the different nanomaterials used to develop sensors to detect microorganisms, graphene has been one of the primary materials due to its exceptional electromechanical properties. Graphene sensors are able to detect microorganisms in both a composite and non-composite manner, due to their excellent electrochemical characteristics such as their high aspect ratios, excellent charge transfer capacity and high electron mobility. The paper depicts the fabrication of some of these graphene-based sensors, and their utilization to detect bacteria, fungi and other microorganisms that are present in very small amounts in different food items. In addition to the classified manner of the graphene-based sensors, this paper also depicts some of the challenges that exist in current scenarios, and their possible remedies.  The inclusion of sensors in different aspects of the lives of human beings has helped improve the quality of life to a great extent. In earlier times, after the initial use of complementary metal-oxide semiconductor (CMOS) circuits  for sensAmong the different applications that the sensors have had a positive impact on, detecting food quality has been of great importance ,45,46. FA lot of research has been conducted on devising methodologies to be used by graphene-based sensors to detect microorganisms in food items. Some of the common techniques include potentiometric sensing , electroThe succeeding examples describe the fabrication process of some types of graphene sensors, and their subsequent utilization for detection purposes of microorganisms in very small amounts. Each of these sensors are formed using different microfabrication techniques, chosen on the basis of the processed materials and final dimensions of the sensors. The processed materials chosen to integrate with graphene to form the prototypes included various polymers and other enzymes that were selective to the target bacteria and other microorganisms present in the food items.Mohanty et al.  showcaseAnother study that highlighted the use of graphene-based sensors to detect microorganisms in food was shown in the research of Gouvêa et al. . These cIn a study conducted by Kotsilkov et al. , nanocomThe research carried out by Moustafa et al.  can be r−5 S/m in-plane and through-plane, respectively. The prototypes had additional advantages such as enhanced antioxidant activity and a mechanically reinforced chitosan matrix. Around 50% of rGO in the nanocomposites increased the tensile strength from 13 MPa to 27 MPa, and the Young’s Modulus from 0.47 GPa to 2.73 GPa. The resultant sensors displayed high tensile strength and decreased water solubility.Barra et al.  showcase2 dimension at 90 °C by treating the GO solutions with HI fumes. Finally, the PLA-graphene composite films were formed by cutting them into dimensions of 15 × 15 cm2, and then treating them with PVP solutions. The solution was prepared as a binder and the free-standing rGO films were delaminated from the composite films. Finally, the free-standing rGO films were placed between two PLA films and heat pressed at a temperature of 65 °C for half an hour. Two types of films, including PLA-rGO and PLA-GO films, were formed and deployed for sensing purposes. The sensors showed excellent permeability capabilities for water and air, as the water vapor permeability was reduced by up to 87.6% due to the synergy between the two processed materials of rGO and PLA. The air permeability of the prototypes also changed as the oxygen permeability was reduced, by a factor of two in both dry and humid conditions. The extensive and tortuous diffusion pathway of rGO allowed the nanocomposites to be formed with excellent processability.Another interesting study in this area is reference , where s−1. The presence of GO in 0.1 wt. % in the composite increased the initial tensile strength from 22.7 ± 1.2 to 6471.6 ± 1775.5 MPa. As the GO content was increased, there was a subsequent increase in the endothermal peak during thermal studies. It also increased the cross-linking degree between the film and water interaction. The nanocomposites were examined for antimicrobial properties using E. Coli K-12 MG 1655 and B. subtillis 102. The composite of 0.6 wt. % showed prime inactivation, which increased by 22.83% for E. Coli and 54.93% for B. subtillis.Grande et al.  investigManikandan et al.  synthesiNaskar et al.  also repHuang et al.  explaineAnother study explaining the use of graphene was highlighted in , where c2) substrates having a thickness of 300 nm. The electrodes were developed using chromium and gold, with 15 nm and 90 nm thicknesses, respectively. The final part included the formation of a monolayer of graphene using a chemical vapor deposition (CVD) process. The repeatability of these G-FETs was achieved using a photolithography process to form samples of 100 × 100 µm. The patterning of graphene was carried out using a PMMA-assisted transfer process. This was executed via chemical treatment, spin-coating, curing and UV-light treatment. The interaction between graphene and the volatile molecules occurred due to the latter’s absorption on the graphene surface via π-π stacking. The sensors could detect indole for a concentration ranging between 10 ppb and 250 ppb with an LOD of 10 ppb.Another study that highlighted the use of graphene for food-related devices was in the research carried out by Lin et al. . GraphenEscherichia coli (E. Coli) through the stemming of anti-E. Coli antibody-coated sensing surfaces. E. Coli in food poisoning, carried out using synthesized anti-E. Coli, followed by using it as a coating on the selective layer on the sensing area of the prototypes.Another study that involved graphene to develop sensors for detecting microorganisms in food is reference . These sE. Coli antibodies. The sample was tested via injection-and-stop and constant injection modes, and showed a resistance change when E. Coli binded to the electrode surface. It was seen that the resistance values increased with the bacterial concentration, with the sensors obtaining an LOD of 12 cfu/mL. The change in resistance can be inferred from the formation of a kinetic barrier for the electron transfer process when the bacteria-antibody conjugation process took place on the surface of the graphene film. This led to intercellular bioactivity on the sensing surface and, in turn, polarizing of the charges on the cell’s surface. As a result, there was an increase in the formation of electron clouds due to the steric hindrance, resulting in a change in the carrier hole density. The resistance study was carried out from 0 to 50 min with increments of 5 min, and showed a logarithmic increase in resistance with an E. Coli concentration that was enhanced from 2.4 × 5 to 2.4 × 56 cfu mL−1.Antibody-coated graphene sensors were used for detection purposes, with the substrate being coated on the two-electrode assembly with a gold/palladium alloy target. Electrical measurement of the resistance values was conducted with respect to the bacterial concentration. This was followed by creating a polydimethylsiloxane (PDMS) microchannel using soft lithography, maintaining the dimensions at 800 µm × 8 mm × 1 mm, perfectly suitable for low-cost technological applications. After rinsing the PDMS microchannels with deionized (DI) water, the sample was incubated with 15 μL of streptavidin, followed by washing it with buffer and DI water and treating it with biotinylated anti-Maskey et al.  synthesiBased on the reviewed examples and some other studies, This paper presented a substantial review of the fabrication of graphene-based sensors, and their utilization as electrochemical sensors. These prototypes were used to detect different chemicals in food. The graphene sensors were fabricated in composite and non-composite forms. The former involves the inclusion of specific nanomaterials and polymers to improve the sensors’ overall sensitivity and mechanical integrity. Apart from detecting the target analyte, some other advantages of these sensors include their wide operating range, low LOD and biocompatible nature. Microorganisms have been detected in very small amounts due to the excellent morphological characteristics of these sensors, such as their high surface area and superior carrier mobility of graphene. One of the requirements of these sensors would be to detect multiple analytes with equal efficiencies. Different polymers, such as PDMS, poly (lactic) acid and others, have been considered to form composites and substrates due to their excellent capability of forming interfacial bonding with graphene allotropes. The sizes of the sensors also vary based on certain factors such as the size of the target analyte, the working mechanism of the prototypes, and the alignment of graphene in the sensing area.While a lot of research has been carried out on developing graphene-based sensors to detect various bacterial samples, some research areas are still ongoing. The production of some of these sensors is on a limited scale and are being tested in controlled environments; their ubiquitous utilization in real-time scenarios would help to minimize food wastage to a great extent. Sensors being tested for a single target should opt for more microorganisms that can affect food. This is because when the food samples are transferred in real-time scenarios between the storage unit and superstores, there is a high probability for the growth of microorganisms over a period. The types of wireless communicational protocols associated with graphene-based sensing devices should be increased and optimized on the bases of the maximum and minimum transmission rates, bandwidth and network size. The types of food samples that can be kept safe and edible in different airtight containers integrated with these graphene-based sensors should also be increased to decrease overall food wastage. The temperature and humidity specifications for the sensors should be further optimized to determine the correlation between the detected microorganisms and available food storage facilities. Implementing some of these propositions effectively will benefit mankind regarding production pressure and food hunger.


The Ni–Fe–graphene composite coating shows an increment of 393.0% in hardness and a decrement of 55.9% in friction coefficient in comparison with 7075 aluminum alloy substrate. The Ni–Fe–graphene composite coating binds tightly to 7075 aluminum alloy with adhesion strength of higher than 6.895 MPa. These make contributions to provide effective protection for aluminum alloys. Surface morphology and corrosion morphology, as well as morphology of the side bound to the substrate, were characterized. The scattered asperities on the surface were proven to be graphene nanoplatelets being wrapped by Ni–Fe, which comprehensively reveals the formation of asperities.The process parameters of electrodeposited Ni–Fe–graphene composite coating on the 7075 aluminum alloy were optimized by the orthogonal experiment. The optimized process parameters were determined as follows: graphene concentration of 1 g L Aluminum and its alloys are extensively applied to aeronautical and aerospace, automobile, and vessel domains because of their merits, including high specific strength, superior electrical and thermal conductivity, and low cost. However, as the demands for materials possessing low friction, high strength, and lightweight continue to escalate, the weak spots of low surface hardness and poor wear resistance for aluminum alloys are not only increasingly prominent, but also limit their application range, and even lead to huge economic loss due to wear failure. Therefore, it is very crucial for aluminum and its alloys to improve surface hardness and reduce friction and wear, utilizing surface modification and reinforcement methods.2, TiN, WC, Cr2O3, AlN, and MWCNT is beneficial to increase hardness and decrease friction coefficient. The properties of different Ni–Fe composite coatings are listed in Electrodeposited Ni–Fe alloy coating has been extensively applied to electronic sensors and micromechanical systems due to its merits such as homogenous structure, eminent magnetic properties , corrosiGraphene, an atom-thick of carbon, has extraordinary mechanical property, including elasticity modulus of 0.5~1.0 Tpa , tensileUp to now, there have been quite limited reports about electrodeposited Ni–Fe–graphene composite coating on the 7075 aluminum alloy and process optimization. In this work, the process parameters of Ni–Fe–graphene composite coatings are optimized by orthogonal design. The morphology, structure, and adhesive strength are investigated as well. 2SO4 to further remove impurities and then were ultrasonic-cleaned in deionized water again.An aluminum alloy (#7075) plate with size of 25 × 25 × 3 mm was used as a cathode for coatings deposition, and a pure nickel plate was used as an anode. The cathode and anode were positioned parallel at an angle of 45 degrees with the plating solution level. The aluminum alloy substrates were polished with 600# emery paper to remove the surface scratches and obtain a uniform surface, and then were sandblasted using 280 mesh glass beads under pressure of about 0.15 MPa to eliminate the oxidation film and increase the coating’s adhesion. Subsequently, the samples were cleaned ultrasonically and chemically treated for a few minutes in 3%NaOH and 3%H4) is shown in In this study, graphene concentration, current density, agitation speed, and temperature were sieved by the orthogonal designing method, and the orthogonal test table of L16 , were about 4~20 nm in thickness and 5~10 μm in diameter. An SEM image of the graphene nanoplatelets is shown in Prior to electrodeposition, in order to ensure the dispersion of graphene in the electrolyte, the bath solution was stirred for 30 min using an ultrasonic emulsification distributor and subsequently stirred mechanically for about 1 h. To maintain the suspension of graphene nanoplatelets in the electrolyte during the deposition process, mechanical agitation was kept constant. After the deposition, samples were cleaned to remove the residual solution, then dried, and then measured. The adhesion strength between the Ni–Fe–graphene composite coating and the aluminum alloy substrate was evaluated by the Elcometer model 106 adhesion tester . It employs the pull-off method to measure the lift-off force required to pull a small area of coating away from the base material. First, the surface of the dolly and Ni–Fe–graphene composite coatings were roughened with 1200 mesh abrasive paper, then degreased in absolute ethyl alcohol by ultrasonic cleaning. E-44 epoxy was mixed with low-molecular-weight 650 polyamide resin in a mass ratio of 1:1. The mixture, namely, adhesive, was applied as an even film to the surface of dolly. The dolly was placed onto the surface of the Ni–Fe–graphene composite coating and pressure was applied to squeeze out the excess adhesive being removed. Then, we placed them in the drying oven with a temperature of 60 °C for 3 h. After curing, the support ring was placed over the dolly, ensuring it lay flat. The pull-off force was applied to the test dolly until the dolly was removed from the surface. The pull-off force was recorded by means of a dragging indicator on an engraved scale. Three samples were prepared under the same process parameters and were measured.The morphology and element composition were characterized using a scanning electron microscope  equipped with energy-dispersive spectroscopy (EDS). −1, keeping the applied normal load  of 1.0 N for 30 min. The test was repeated three times for each material under the same test conditions. The Vickers hardness of the Ni–Fe–graphene composite coatings was examined using a microhardness tester  with a load of 100 g applied for 10 s. Five data points were averaged for each sample. All coatings and substrate suffered from friction testing on a ball-on-disk tribometer  under dry air environment at room temperature. The counterpart ball for wear test was a GCr15 steel ball with diameter of 3 mm. The test was carried out at the sliding velocity of 0.1 m s−1, current density of 9 A dm−2, agitation speed of 250 r min−1, and temperature of 60 °C, corresponding to experiment No. 4 in −1, current density of 5 A dm−2, agitation speed of 100 r min−1, and temperature of 60 °C, corresponding to experiment No. 6 in The process parameters of the Ni–Fe–graphene composite coatings were optimized according to the hardness and friction coefficient (COF). The orthogonal test results are shown in In addition to the process parameters’ optimization by analyzing orthogonal test results visually, range analysis was conducted on the basis of orthogonal test results, and the range analysis results are shown in 1, A2, A3, and A4 are responding to the average hardness of the same level under different factors . B is representative of COF, and B1, B2, B3, and B4 are responding to the average COF of the same level under different factors . Ri is representative of hardness range and Rj is representative of COF range. The influence degree of different factors on properties is confirmed and the higher the value of the range, the greater the degree of influence. A is representative of hardness, and AThe influence degree on the hardness of the Ni–Fe–graphene composite coating of different factors, from the highest to the lowest, is graphene concentration, current density, agitation speed, and temperature. The optimized parameters according to the average hardness under the different levels are responding to experiment No. 4, which agrees with the optimized parameters by analyzing orthogonal test results visually. −1, current density of 9 A dm−2, agitation speed of 100 r min−1, and temperature of 40 °C, which is different from any experiment in However, the influence degree on the COF of the Ni–Fe–graphene composite coating of different factors, from the highest to the lowest, is current density, agitation speed, graphene concentration, and temperature. The optimized parameters according to the average COF under the different levels are graphene concentration of 3 g L−1, current density of 9 A dm−2, agitation speed of 250 r min−1, and temperature of 60 °C. The hardness and friction coefficients of the Ni–Fe–graphene composite coating prepared under these parameters are 912.6 HV and 0.1990, respectively. In comparison with 7075 aluminum alloy substrate, the Ni–Fe–graphene composite coating shows an increment of 393.0% in hardness and a decrement of 55.9% in friction coefficient.As a result, the optimized process parameters are graphene concentration of 1 g LThe surface morphology and element distribution of Ni–Fe–graphene composite coatings are shown in The element compositions of the Ni–Fe–graphene composite coatings from EDS analysis are shown in 3. The corrosion morphology is presented in In order to further prove the asperities being scattered on the surface, the Ni–Fe–graphene composite coatings were corroded in 30 vol% HNO2+ and Fe2+ ions are reduced preferentially on the GNPs after GNPs are deposited on the cathode, which realize the incorporation of GNPs into the composite coating. Due to excellent electrical conductivity and the large specific surface area of graphene, the deposition rate of metal ions on the GNP surface exceeds that on the reduced Ni–Fe alloy, which modifies the surface morphology and induces the formation of asperities by offering more active sites for metal atoms [2+ and Fe2+ ions continue to be reduced on the surface as electrodeposition proceeds, which generates a layer structure on the wall of holes. The results reveal the formation of asperities and electrodeposited graphene composite coatings. Nial atoms ,34,35. WDollies were separated from between the Ni–Fe–graphene composite coating and the substrate. The separated area is equivalent to 30%, as shown in −1, current density of 9 A dm−2, agitation speed of 250 r min−1, and temperature of 60 °C. The Ni–Fe–graphene composite coating shows an increment of 393.0% in hardness and a decrement of 55.9% in friction coefficient in comparison with the 7075 aluminum alloy substrate. The Ni–Fe–graphene composite coating binds tightly to the 7075 aluminum alloy and the adhesion strength is higher than 6.895 MPa. The incorporation of graphene modifies the surface morphology and induces the formation of asperities. These asperities are graphene being wrapped completely or incompletely, with Ni–Fe alloy being verified by surface morphology, composition, and corrosion surface morphology. Simultaneously, layered structures in the corrosion holes clarify the formation of electrodeposited graphene reinforced metal matrix composite coating.A Ni–Fe–graphene composite coating was prepared on the 7075 aluminum alloy using the electrodeposition technique, and the process parameters were optimized by the orthogonal experiment. The optimum process parameters are graphene concentration of 1 g L


The combined score of PD-L1-positive cells including tumor cells and tumor-associated macrophages (TAMs) was significantly associated with preoperative plasma sPD-L1 levels. In patients with high levels of preoperative plasma sPD-L1, the probability of 5-year RFS was significantly poor for patients with low PD-L1 expression intensity of tumor cells (tcPD-L1) compared with those with high tcPD-L1 . In former group, PD-L1-positive TAMs were markedly infiltrating compared with those from latter group . In NSCLC, plasma sPD-L1 can reflect the accumulation of PD-L1-posotive TAMs, not just PD-L1-positive tumor cells. In patients with high levels of preoperative plasma sPD-L1, the prognoses after surgery depends on which PD-L1-positive cells, tumor cells or TAMs, are the primary source of the sPD-L1. Thus, measuring both plasma sPD-L1 levels and PD-L1 expression status of tumor cells and TAMs is of benefit for assessment of postoperative prognosis in operable NSCLC.Programmed cell death-ligand 1 (PD-L1) on tumor cells can be degraded to soluble form (sPD-L1) and enter circulation, however, the clinical significances of sPD-L1 in peripheral blood remains to be elucidated in non-small-cell lung cancer (NSCLC). We monitored plasma sPD-L1 levels during perioperative periods and evaluated PD-L1-positive cells in tumor tissues in patients with operable NSCLC. Then the correlation between preoperative plasma sPD-L1 levels and relapse-free survival (RFS) was analyzed retrospectively. In patients who underwent radical surgery (The online version contains supplementary material available at 10.1007/s00262-023-03527-y. Since the emergence of immune checkpoint inhibitors as one of the standard therapeutics for non-small cell lung cancer (NSCLC) –4, thereIn patients with NSCLC, measuring the percentage of PD-L1-positive cancer cells in cancer tissues by immunohistochemistry (IHC) is useful for predicting the efficacy and application of anti-PD-1 and -PD-L1 therapeutic antibodies –9. In thPrevious studies reported that soluble PD-L1 (sPD-L1) could be detected in the peripheral blood of NSCLC patients –20, howeTo reveal the biological and clinical significances of sPD-L1 in peripheral blood and answer these questions, in this study, we measured sPD-L1 levels in peripheral blood in settings that were different from previous studies. We compared plasma sPD-L1 levels before and after surgery in patients with NSCLC, meaning a comparison of sPD-L1 levels in the presence and absence of tumors. Additionally, we investigated association of preoperative plasma sPD-L1 with RFS after surgery, and explored the PD-L1-expressing cell type that could influence the prognosis of patients.In total, 69 patients who underwent surgery for pulmonary tumors at Shiga University of Medical Science Hospital between November 2013 and October 2015 were enrolled in this study. Among them, 63 patients were pathologically diagnosed with NSCLC . The 75th percentile value in the investigated cohort was used as the cutoff value, and a high level of plasma sPD-L1 was defined as cases where the level was higher than the cutoff.Whole tumor Sects. (4-μm-thick) of formalin-fixed paraffin-embedded tissue were deparaffinized in xylene and rehydrated in ethanol and distilled water. Antigen retrieval was performed by microwaving sections in Universal HIER antigen retrieval reagent (Abcam) for 20 min. Endogenous peroxidase activity was blocked by treatment with Peroxidase Block  for 10 min, and non-specific binding was blocked by treatment with Protein Block serum-free Ready-to-use (DAKO) for 10 min at room temperature. The sections were then incubated overnight at 4 °C with anti-human PD-L1 monoclonal antibody . The sections were then incubated with Rabbit-specific IHC polymer detection kit and visualized using DAB substrate (both Abcam). Finally, sections were counterstained with hematoxylin. For negative control staining, the anti-PD-L1 primary antibody was replaced with a rabbit IgG monoclonal antibody (Abcam).To evaluate the PD-L1 expression status of NSCLC cells following IHC staining, we used a semi-quantitative scoring method that reflects both the intensity and extent of PD-L1 expression of tumor cells and is expressed as the PD-L1 expression score (H-score), as described previously . BrieflyTo evaluate the cell density of PD-L1-positive TAMs, the total number of PD-L1-positive TAMs was counted in three randomly selected fields under 400 × magnification, and the cell density of PD-L1-positive TAMs was calculated for each field of view by dividing the cell counts by the area of the field of view. Sections were independently examined by two researchers, including a pathologist, and the average of the cell densities in each field of view was calculated.Human CD14-positive peripheral blood mononuclear cells (PBMCs)  were cultured in AIM-V medium  in the presence of granulocyte macrophage colony-stimulating factor for Type 1 (M1) and macrophage colony-stimulating factor for Type 2 (M2) macrophages  for 6 d. Then, the cells were stimulated with 1 μg/mL lipopolysaccharide for 24 h to generate activated M1 and M2 cells. The culture supernatants were collected, and levels of sPD-L1 were measured by ELISA as described above. The expression levels of specific markers for each type of macrophage were evaluated by flow-cytometry using a BD FACS Calibur, and the data were analyzed using BD CellQuest Pro software . Antibodies used for detection were PE mouse anti-CD80  and anti-CD229 (interferon-gamma receptor)  for M1, PE mouse anti-CD163  and anti-CD206  for M2, and PE mouse anti-PD-L1 antibody  for PD-L1.U test, and comparisons between more than three groups were analyzed using ANOVA. Pearson’s product-moment correlation coefficient was used to analyze the correlation between two continuous variables. Relapse-free survival (RFS) after surgery was calculated using Kaplan–Meier analysis and was compared with the log-rank test. All analyses were performed using SPSS Statistics 25.0 software .For continuous variables, comparisons between two groups were analyzed using the Mann–Whitney R = 0.0071, P = 0.293)  , and the median plasma sPD-L1 level was 63.6 pg/mL, with a range of 0.0 to 204.6 pg/mL. Using the H-score as a semi-quantitative evaluation of the expression intensity of PD-L1 on tumor cells (tcPD-L1), the median tcPD-L1 expression score was 97.1, with a range of 0.0 to 244.9. Then, we analyzed the correlation between preoperative plasma sPD-L1 levels and tcPD-L1 expression score. However, a significant correlation was not observed between two  and in smokers compared with never smokers . However, sPD-L1 levels were not associated with age , tumor size , pathological type , postoperative pathological stage , tumor cell grade , lymphatic invasion , or microvessel invasion of tumor cells .Next, we analyzed correlations between preoperative plasma sPD-L1 levels and clinicopathological factors . The data demonstrated that preoperative plasma sPD-L1 levels were significantly higher in male compared with female patients (median: 65.7 n = 61) (Supplementary Table 1). The median preoperative serum sPD-L1 level was 63.4 pg/mL, and 1 month after surgery, the median sPD-L1 level (n = 55) had significantly increased to 72.2 pg/mL (P < 0.001)  had significantly decreased to the preoperative level     were positive for PD-L1, especially those that had gathered in specific regions Fig. a. On then = 55) (Supplementary Table 2) were classified into two groups according to preoperative plasma sPD-L1 levels: the high sPD-L1 group (≥ 80 pg/mL) and the low sPD-L1 group (< 80 pg/mL), as described earlier. Kaplan–Meier analysis revealed that postoperative RFS tended to be shorter in the high sPD-L1 group (n = 18) than in the low sPD-L1 group (n = 37), which had 5-year relapse-free probabilities of 58.8% and 67.9%, respectively   than for the low tcPD-L1 expression group (n = 38), which had 5-year relapse-free probabilities of 76.5% and 59.3%, respectively   and the low tcPD-L1 expression group (< 150), as in a previous report . Kaplan–2) and the low PD-L1-positive TAMs group (< 150/ mm2) (Area under the curve = 1.000). Kaplan–Meier analysis revealed that postoperative RFS tended to be longer for the low PD-L1-positive TAMs group (n = 30) than for the high PD-L1-positive TAMs group (n = 25), which had 5-year relapse-free probabilities of 72.8% and 54.5%, respectively   compared with those in the high sPD-L1–high tcPD-L1 group (n = 8), which had 5-year relapse-free probabilities of 33.3% and 87.5%, respectively  , the cell density of PD-L1-positive TAMs was significantly high compared with that in the high sPD-L1–high tcPD-L1 group (n = 8)    and 2 (M2) macrophages were induced from human PBMCs, and these cells were confirmed to express PD-L1 . ELISA demonstrated that both M1 and M2 cells released sPD-L1 into the culture supernatant, and the levels significantly increased following activation with lipopolysaccharide , which are a dominant cell type in the stroma, can express PD-L1 following stimulation by interferon-gamma (IFN-γ) and that PD-L1-positive CAFs are present in NSCLC tissues . In thatIn addition to the data that plasma sPD-L1 levels were significantly elevated 1 month after surgery, we found no correlation between preoperative plasma sPD-L1 levels and tcPD-L1expression intensity, which is consistent with the results of previous reports . In thisNext, we investigated the clinical significance of sPD-L1 in peripheral blood. Previous papers have reported that high sPD-L1 levels in peripheral blood are associated with poor prognosis in patients with advanced NSCLC (reviewed in ref. 24). In addition, in our study, patients with high preoperative plasma sPD-L1 levels tended to have shorter RFS after surgery. However, when the high sPD-L1 group was further classified into two subgroups by tcPD-L1 expression intensity, it was found that prognosis was significantly different between the subgroups with high and low tcPD-L1 expression. These data demonstrated that RFS after surgery was significantly shorter in the group with high plasma sPD-L1 and low tcPD-L1 expression compared with the group with high plasma sPD-L1 and high tcPD-L1 expression. This may depend on which cells, tumor cells or TAMs, are the primary source of the sPD-L1 in peripheral blood.We have previously reported that high tcPD-L1 expression is a good prognostic biomarker for patients with early-stage NSCLC . This isWe suggested that PD-L1-positive TAMs contributed to the elevated plasma sPD-L1 levels and poor prognosis. However, there are several limitations to this study. First, the number of PD-L1-positive TAMs in tumor tissues was assessed by their density in the tissue. The sPD-L1 level in peripheral blood can be affected by the product of the cell density of PD-L1-positive TAMs and tumor volume; we did not consider tumor volume. Although we examined correlations between plasma sPD-L1 levels and the density of PD-L1-positive TAMs in combination with maximum tumor diameter, no clear data were obtained (data not shown). Second, as mentioned earlier, there are other PD-L1-positive cells in the tumor stroma , 23, andIn conclusion, sPD-L1 levels in peripheral blood were significantly elevated 1 month after surgery compared with preoperative levels despite the absence of tumors. Among patients with high levels of preoperative plasma sPD-L1, those with low tcPD-L1 expression had significantly worse postoperative prognoses than those with high tcPD-L1 expression. In the former group, the cell density of PD-L1-positive TAMs was significantly higher, and suppression of antitumor immune responses by TAMs may be the cause of poor prognosis. The sPD-L1 in peripheral blood can be derived from PD-L1-positive TAMs, not just PD-L1-positive tumor cells. Thus, in patients with operable NSCLC, measuring both plasma sPD-L1 levels and PD-L1 expression status of tumor cells and TMAs is of benefit for assessment of postoperative prognosis.Supplementary file1 (PPTX 96 kb)Supplementary file2 (PPTX 71 kb)Supplementary file3 (XLSX 10 kb)Supplementary file4 (XLSX 10 kb)Below is the link to the electronic supplementary material.


Background: Radiation-induced dermatitis (RID) is one of the most prevalent side-effects of conventional cancer therapies; however, there is no standard treatment for its prevention. Therefore, this study aimed to evaluate the comparative efficacy and safety of Jaungo (mainly composed of Lithospermum erythrorhizon Siebold & Zucc. and Angelica sinensis (Oliv.) Diel) and the water-in-oil-type non-steroidal moisturizer for the prevention of RID in patients with breast cancer (BC).Methods: This is a prospective, single-blind, pilot randomized controlled trial. Between March 2021 and July 2022, 50 patients were randomly selected to use Jaungo or the moisturizer while undergoing postoperative radiation therapy (RT). Assessments were conducted nine times—every week while the patients underwent RT and 2 weeks after the end of therapy. The primary outcome was the incidence rate of RID grade ≥2. The secondary outcomes were the incidence rate of maximum grade RID, time to RID onset, RID-related quality of life (QOL) score, pain intensity, and adverse events.Results: The incidence rate of RID grade ≥2 was 24.0% and 20.0% in the Jaungo and the moisturizer groups, respectively, with no significant difference between the groups (p = 0.733). Regarding the secondary outcomes, the incidence rate of maximum grade RID (p = 0.890), mean time to RID onset (p = 0.092), cumulative incidence rate of RID (p = 0.280), RID-related QOL score, and maximum pain intensity (p = 0.844) also did not differ significantly between the groups. None of the subjects in either group experienced severe adverse effects, although one participant in the moisturizer group had mild fever and insomnia.Conclusion: These findings suggest that Jaungo has preventive efficacy without severe side-effects against RID in patients with BC that is comparable to that of the water-in-oil type non-steroidal moisturizer. Further extensive randomized controlled trials with larger sample sizes are warranted to validate our findings.Clinical Trial Registration: Clinical Research Information Service (CRIS), https://cris.nih.go.kr, identifier KCT0005971. Radiation therapy (RT) is one of the most common conventional therapies for patients with cancer . More thSeveral studies have been conducted on possible strategies for reducing the occurrence of RID after RT in patients with BC; however, no standard preventive treatment for RID has been clearly demonstrated to be effective . TherefoA water-in-oil type non-steroidal moisturizer cream containing hyaluronic acid as the main component showed significant efficacy in preventing and reducing RID compared to an emollient base cream in terms of ameliorating skin toxicity, burning sensations, and erythema in the irradiated area in patients with BC . It was Lithospermum erythrorhizon Siebold & Zucc.  and Angelica sinensis (Oliv.) Diels [Apiaceae/Umbelliferae; Angelica sinensis), is registered for use as a topical drug for dermatitis in Korea. The symptoms approved by the Korean Ministry of Food and Drug Safety for the use of Jaungo are rough skin, frostbite, heat rash, anus laceration, and skin inflammation. It is commonly used to treat skin injuries due to abrasions, frost, or burns. It is also widely used in clinical practice to prevent RID in cancer patients (Jaungo (Shiunko in Chinese and Japanese), a traditional herbal ointment mainly composed of patients . Severalpatients . A priorpatients . Case sepatients . HoweverConsidering the limited options for preventing RID and the results of previous studies, we designed this prospective, randomized, single-blind pilot study (CRIS registration number KCT0005971) to compare two topical agents commonly used for RID—Jaungo and the water-in-oil type non-steroidal moisturizer. This is the first randomized controlled trial (RCT) to evaluate the preventive efficacy of topically applied Jaungo and compare it with that of the water-in-oil type non-steroidal moisturizer in RID patients with BC.The patient eligibility criteria were as follows: pathologically confirmed invasive BC, having undergone breast-conserving surgery, and adjuvant RT planned after surgery. Patients with a history of RT for any reason, unhealed scars in the breasts, soft tissue disease, or uncontrolled diabetes mellitus with HbA1c ≥ 6.5% were excluded. Patients with a metastatic cancer stage were also excluded. This study was approved by the Institutional Review Board (IRB) of Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea (IRB number KHNMCOH-2020-12-001-002).Between March 2021 and July 2022, 50 patients were prospectively enrolled and randomly allocated to the Jaungo group or the moisturizer group based on random numbers generated using a 2 × 2 randomized permuted block design by an independent statistician. The sample size was estimated based on the grade of Radiation Therapy Oncology Group (RTOG)  and NatiL. erythrorhizon, Angelica sinensis, sesame oil, beeswax, and lard. The detailed compositions and the quality of control of Jaungo are presented in the ®, Pharmbio Korea Corporation, Seoul, Republic of Korea; expiration date 04.23.2023) in the same manner. Owing to the possibility of bolus effect, neither agent was to be applied within 4 h after an RT session, and both were cleaned off from the irradiated region immediately before each session. Jaungo and the moisturizer were contained in individually packaged tubes, and each tube was stored at room temperature between 1 and 30° in an airtight container. If skin irritation, a local rash, or itching occurred, the application of the agents was stopped by the assessors. No other prophylactic topical agents for RID were allowed to be used in either group, but topical and intravenous antibiotics were allowed as rescue medicine.Participants allocated to the intervention group, i.e., the Jaungo group, were instructed to apply Jaungo . Jaungo is an external ointment consisting of 10) ≥ 60 Gy according to the National and International Guidelines. For participants who had risk factors for regional recurrence, such lymphovascular or axillary lymph node invasion, regional lymph node irradiation was also performed.All subjects underwent 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT) for 5–7 weeks with five fractions each week, and the tumor bed was treated with a biological equivalent dose  performance status, final educational background, disease history, smoking and diabetes mellitus status, was collected. Information on clinical characteristics, such as breast volume, irradiation side (right or left), histology results and malignant tumor cell molecular subtype, cancer stage based on TNM staging, lymph node irradiation (Yes/No), and concurrent chemotherapy (Yes/No) was also recorded. For the assessment of outcomes, the severity and date of onset of RID, QOL, skin reaction symptoms, and pain intensity, including that of maximum pain related to RID, were evaluated based on the scale of Radiation Therapy Oncology Group (RTOG) criteria . OutcomeThe incidence rate of RID of RTOG grade ≥2 was evaluated as the primary outcome in this study. As secondary outcomes, the time to RID onset, incidence rate of maximum grade RID, CSSP, Skindex-29, and NRS scores, and adverse events (AEs) based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 were assessed at the start (visit 1) and end (visit 8) of RT and 2 weeks later (visit 9) to compare between the Jaungo and moisturizer groups .t-test or Mann–Whitney U test. The types, frequencies, and severity of AEs were also assessed; events that were determined to be caused by each intervention are separately analyzed and reported. All analyses were performed using SPSS version 25.0  based on the intention-to-treat (ITT) set. All tests were two-sided, and differences with a p value <0.05 were considered statistically significant.The characteristics of all participants are reported as mean and 95% confidence interval (95% CI) values for continuous variables or frequencies and percentages for categorical variables. The difference in incidence rate of RID of RTOG grade ≥2, the primary outcome, between the two groups was assessed using the Chi-square test. Among the secondary outcomes, the difference in incidence rate of maximum grade RID between groups was assessed using the Chi-square test, between time to RID onset using Kaplan-Meier analysis, and between CSSP, Skindex-29, and maximum NRS scores using the independent samples p = 0.672). Three participants in the Jaungo group and one in the moisturizer group refused to use topical agents during the study and declined to participate. One more participant in the Jaungo group was excluded from the analysis due to loss to follow-up. Therefore, 21 participants in the Jaungo group and 24 in the moisturizer group completed treatment, and all 50 participants were included in the efficacy and safety assessment based on ITT analysis . The body mass index (BMI) was 25.0 ± 5.0 and 24.2 ± 3.3 kg/m2, respectively, with no significant differences in height, weight, or BMI. The mean breast volume calculated using the RT planning computer was 671.1 ± 316.2 versus 642.9 ± 321.8 cc, respectively. The number of participants who underwent concurrent chemotherapy during RT was five (20.0%) and three (12.0%) in each group, and all received taxol-based chemotherapy. There was no statistically significant difference (p = 0.702). The most common type of histology was invasive ductal carcinoma, followed by ductal carcinoma in situ. In both groups, there was one participant (4.0%) with confirmed triple-negative cancer cell molecular subtype, which is usually more aggressive than the estrogen receptor-/progesterone receptor-positive or human epidermal growth factor receptor-positive types (The characteristics of the participants are summarized in ve types . Regardip = 0.733). There were no subjects with RID over grade 2, and 12.0% (three subjects) and 16.0% (four subjects) did not experience RID during the entire trial period. There was no significant difference in the incidence of maximum grade RID between the two groups. The mean time to RID onset was 26.5 ± 11.8  versus 30.4 ± 10.3  days, respectively (p = 0.092). In addition, the cumulative incidence of RID, as assessed using the log-rank test, did not differ significantly between the groups (p = 0.280) (p = 0.536).The outcome results are summarized in = 0.280) . Among pp = 0.045), but pain scores at other visits and maximum pain score did not differ significantly between the groups.CSSP and Skindex-29 were used to assess the effects of RID on participant QOL. The CSSP scores at visit 1, 8, and 9 did not differ significantly between the two groups. The Skindex-29 total score  also showed no difference at any visit. However, when the Skindex-29 subscale scores were separately analyzed, there were significant differences between the groups with regard to the scores for the following items: ‘My skin condition burns or stings,’ and ‘My skin itches’ on the symptoms scale at visit 8, ‘My skin condition affects how well I sleep’ at visit 8 and ‘I tend to stay at home because of my skin condition’ at visit 9 on the functioning scale, and ‘My skin condition makes me feel depressed’ at visit 9 on the emotion scale. The scores for 29 Skindex-29 items are presented in the In the safety analysis, only one participant in the moisturizer group had mild fever and grade 1 insomnia based on CTCAE version 5.0. Both symptoms were evaluated as likely unrelated to the topical agent and resolved without discontinuing treatment or RT. Additionally, there were no severe AEs during the entire trial period.RID is one of the most common side-effects of RT. Patients with RID can experience various symptoms, such as edema, pruritis, erythema, moist desquamation, ulceration, necrosis, and hemorrhage in the irradiated regions, and have delayed or discontinued conventional cancer therapies because of the events . Accordi10 ≥ 60 Gy. The mean age in the Jaungo group was significantly higher than that in the moisturizer group. Based on the prior background, since it has been reported that the incidence of RID increases with age, participants who used Jaungo could be expected to be at a higher risk of RID incidence than those who used the moisturizer. However, our results showed no significant differences in the incidence rate of RID grade ≥2, maximum grade, mean time to RID onset, or cumulative incidence of RID between the two groups. These outcomes support the potential benefit of Jaungo in preventing RID in patients with BC independently of risk factors, and also indicate that it is comparable to the water-in-oil type non-steroidal moisturizer.There are various risk factors for RID in patients with BC. Regarding therapy-related factors, the dose and duration of RT and concurrence with other conventional cancer therapies have been reported to affect the incidence of RID on irradiated skin. In addition, high breast volume, older age, high BMI, poor ECOG performance status, smoking, and alcohol consumption are patient-related factors associated with the early development of RID . Considep < 0.0001), burning sensations (p = 0.039), and moist desquamation within radiation lesions (p = 0.02) compared to the other topical agent without the key components  is a traditional herbal ointment standardized according to the Korean Pharmacopeia. Its main components are Lithspermi radix and Angelica sinensis. The Korea Food and Drug Safety Administration (KFDA) has approved its use as a topical drug for dermatitis. The active ingredients have been identified as shikonin, acetylshikonin, ferulic acid, and decursin, which have been reported to promote soft tissue formation, wound regeneration, and skin healing due to their antibacterial and anti-inflammatory properties (ytokines . Accordiytokines . Jaungo ytokines . Therefoytokines . In addiytokines . TherefoThis study provides evidence that Jaungo has comparable efficacy to the moisturizer for RID in patients with BC. However, it has some limitations. First, this trial was a pilot study with a small sample size. Although the number of patients in each group was estimated statistically based on previous research, further larger sample size RCTs are needed. Second, this study was conducted in a single-blind manner, which means that the subjects knew whether they applied Jaungo or the moisturizer. This may have been a confounding factor; therefore, placebo-controlled trials are required to ensure double-blinding. Despite these limitations, this is the first pilot RCT to evaluate the comparative efficacy and safety of Jaungo and the moisturizer for RID in patients with BC. We believe that the results of this study will encourage further well-designed, double-blind, large-scale RCTs on preventing RID related to conventional cancer therapies.L. erythrorhizon and Angelica sinensis extracts, has comparable efficacy in preventing RID in patients with BC to a water-in-oil-type non-steroidal moisturizer cream currently used in clinical practice. However, large-sample, double-blind RCTs with placebo-controlled are required to fully define the efficacy and safety of Jaungo in preventing RID in patients with BC. (Jaungo, a traditional herbal ointment which mainly consists of with BC. .


Total joint arthroplasty (TJA) is one of the most common surgical operations performed in the US. Periprosthetic joint infection (PJI) is a daunting complication of TJA and is associated with high morbidity. Previous studies have shown that racial disparities exist in postoperative complications of TJAs, including readmissions and mortality. However, it is unclear if such disparities also exist for PJI.A single large hospital system database was used to identify all patients who underwent either primary total knee arthroplasty (TKA) or total hip arthroplasty (THA) between January 2018 and December 2021. Patients were stratified by self-identified racial categories. PJI was defined by ICD-9/10 coding. We present descriptive data as frequencies and percentages for categorical variables and means and standard deviations for continuous variables. We used chi-square tests to estimate crude risk ratios (cRR) and 95% confidence intervals (CIs) for PJI by race.A total of 11,818 patients were included in the final analysis. The majority (96.6%) of patients identified as non-Black (Table 1). The mean age was 69.4 (±10.3) years for non-Black patients and 65.5 (±11.5) years for Black patients. Females represented the majority of non-Black and Black patients who underwent TJA . The majority of TJAs were TKAs for both non-Black and Black patients . The incidence of PJIs was 1.6% among non-Black patients compared to 3.3% among Black patients (cRR (95% CI): 1.99 (1.17 – 3.39); p=0.0112). The majority of PJIs occurred post TKA (Table 1).Preliminary findings suggest that racial disparities exist in PJIs. These findings were not adjusted for possible confounding factors such as age, sex and comorbidities. Future studies are needed to determine if such disparities persist when other factors are considered.Antonia Chen, MD, MBA, Adaptive Phage Therapeutics: Advisor/Consultant|Adaptive Phage Therapeutics: Grant/Research Support|Avanos: Advisor/Consultant|BICMD: Advisor/Consultant|Convatec: Advisor/Consultant|Elute: Grant/Research Support|Ethicon: Advisor/Consultant|GLG: Advisor/Consultant|Guidepoint: Advisor/Consultant|Heraeus: Advisor/Consultant|Hyalex: Stocks/Bonds|IlluminOss: Stocks/Bonds|Irrimax: Advisor/Consultant|Irrimax: Stocks/Bonds|Journal of Bone and Joint Surgery: Deputy Editor|Osteal Therapeutics: Advisor/Consultant|Osteal Therapeutics: Stocks/Bonds|Peptilogics: Advisor/Consultant|Peptilogics: Grant/Research Support|Pfizer: Advisor/Consultant|SLACK Incorporated: royalties|Smith and Nephew: Advisor/Consultant|Sonoran: Stocks/Bonds|Stryker: Advisor/Consultant|Taylor & Francis Group: Royalties|UpToDate: Royalties