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Legionella is an underdiagnosed and underreported etiology of pneumonia. Legionella pneumophila serogroup 1 (LpSG1) is thought to be the most common pathogenic subgroup. This assumption is based on the frequent use of a urinary antigen test (UAT), only capable of diagnosing LpSG1. We aimed to explore the frequency of Legionella infections in individuals diagnosed with pneumonia and the performance of diagnostic methods for detecting Legionella infections. We conducted a scoping review to answer the following questions: (1) “Does nucleic acid testing (NAT) increase the detection of non-pneumophila serogroup 1 Legionella compared to non-NAT?”; and (2) “Does being immunocompromised increase the frequency of pneumonia caused by non-pneumophila serogroup 1 Legionella compared to non-immunocompromised individuals with Legionnaires’ disease (LD)?”. Articles reporting various diagnostic methods (both NAT and non-NAT) for pneumonia were extracted from several databases. Of the 3449 articles obtained, 31 were included in our review. The most common species were found to be L. pneumophila, L. longbeachae, and unidentified Legionella species appearing in 1.4%, 0.9%, and 0.6% of pneumonia cases. Nearly 50% of cases were caused by unspecified species or serogroups not detected by the standard UAT. NAT-based techniques were more likely to detect Legionella than non-NAT-based techniques. The identification and detection of Legionella and serogroups other than serogroup 1 is hampered by a lack of application of broader pan-Legionella or pan-serogroup diagnostics.

Immunomodulators such as tumour necrosis factor (TNF) inhibitors are used to treat autoimmune conditions by reducing the magnitude of the innate immune response. Dampened innate responses pose an increased risk of new infections by opportunistic pathogens and reactivation of pre-existing latent infections. The alteration in immune response predisposes to increased severity of infections. TNF inhibitors are used to treat autoimmune conditions such as rheumatoid arthritis, juvenile arthritis, psoriatic arthritis, transplant recipients, and inflammatory bowel disease. The efficacies of immunomodulators are shown to be varied, even among those that target the same pathways. Monoclonal antibody-based TNF inhibitors have been shown to induce stronger immunosuppression when compared to their receptor-based counterparts. The variability in activity also translates to differences in risk for infection, moreover, parallel, or sequential use of immunosuppressive drugs and corticosteroids makes it difficult to accurately attribute the risk of infection to a single immunomodulatory drug. Among recipients of TNF inhibitors, Mycobacterium tuberculosis has been shown to be responsible for 12.5-59% of all infections; Pneumocystis jirovecii has been responsible for 20% of all non-viral infections; and Legionella pneumophila infections occur at 13-21 times the rate of the general population. This review will outline the mechanism of immune modulation caused by TNF inhibitors and how they predispose to infection with a focus on Mycobacterium tuberculosis, Legionella pneumophila, and Pneumocystis jirovecii. This review will then explore and evaluate how other immunomodulators and host-directed treatments influence these infections and the severity of the resulting infection to mitigate or treat TNF inhibitor-associated infections alongside antibiotics.

Abstract This report describes the development and characterization of a comprehensive collection of CHO cell glycosylation mutants with significant potential for advancing glycobiology and biotechnology. EPO-Fc and trastuzumab, two model molecules, were produced using these mutants to assess the effects of mutated glycogenes, and LC-MS/MS analysis was employed to quantitatively analyse their N-glycans. EPO-Fc exhibited exclusively homogeneous Man9 glycans only when nearly all α-mannosidases in the genome were inactivated, except lysosomal MAN2B1. Some mutants lacking GnT-I activity produce mostly Man5 N-glycans, while their O-glycan and glycolipid profiles can differ due to other mutations in the cell. GnT-II deficiency prevents GnT-V from adding GlcNAc to the core N-glycan, resulting in branches attaching solely to the α1,3-linked mannose, leaving the α1,6-linked mannose free. The mutant-produced antibody’s single-branched glycan contains more sialic acid than the dual-branched glycans produced in CHO-K1 cells. Trastuzumab produced in these mutants provided insights into how Fc N-glycans impact the antibody’s interaction with FcγR1 and FcγR2a, FcγR3a, and their influence on antibody-dependent cellular cytotoxicity (ADCC). In the study of Fc glycans in Fc-FcγR1 and FcγR2a interactions, we observed a consistent glycan-related impact on binding to both receptors, indicating a common interaction mechanism between Fc glycans and both FcγRI and FcγRIIa. CHO mutants produced trimeric gp120 demonstrated distinct reactivity with multiple broadly neutralizing anti-HIV antibodies, confirming the involvement of gp120 glycans in interactions with specific broadly neutralizing antibodies. Finally, one of the mutants produced human β-glucocerebrosidase with uniform Man5 N-glycans, showcasing its potential for glycoengineered production and enhancement in therapeutic efficacy.

The failure of the building work is due to the structure failing to function and can also cause material losses and can even cause fatalities. Because of that, excellent and careful anticipation is needed. In this regard, the re-search that will be carried out is monitoring the structure's health by identifying structural damage based on vi-bration tests. Modal structural parameters are determined based on the vibration output using the Second Order Blind Identification algorithm created by numerical simulation in the MATLAB application. The method in this research is a laboratory experiment with two testing models, namely the modal parameter values of the typical truss structure and the damaged truss structure, using the Second Order Blind Identification algorithm method. Furthermore, analyzing the indications of structural damage from the estimated modal parameters, the accuser, and the effectiveness of the Second Order Blind Identification algorithm method is feasible to use. The results showed that the Hp sensor recording data that had been processed were the health15mts.mat and dam-age15mts.mat files loaded into the SOBI program, and the predicted value of the natural frequency of typical structures was 31,9072 rad/s, and damaged structures were 22,6089 rad/s. From the expected frequency, the frequency ratio value is 41.127 %. According to the Steel Frame Bridge Inspection Regulation No.005/BM/2009 Guidelines for Construction and Building of the Ministry of Public Works, Directorate General of Highways, if it exceeds 20%, it can be categorized as critical.

Amy Blevins served as the Medical Library Association president from 2023-2024. In this presidential biography, authors outline a history of Blevins' recruitment to the career, career development, and impact on the association and the profession.

Purpose: To characterize radiographic foot/ankle bony abnormalities in elite-level, asymptomatic male basketball athletes and to investigate the association between anthropometric (age, height, weight) or sport-specific characteristics (total exposures, player position, pregame ankle taping) and the prevalence of abnormal radiographic findings in asymptomatic basketball athletes. Methods: Elite-level basketball players who underwent routine, preseason static radiographic imaging, including anteroposterior, lateral, and mortise views of the ankle were included. Radiographs were collected from asymptomatic athletes participating in preseason history and physical with negative anterior drawer/talar tilt test. Radiographs were evaluated by a musculoskeletal radiologist and board-certified orthopaedic surgeon; kappa statistics were used to evaluate agreement. Results: Fifty-four basketball players (34 collegiate, 20 professional; mean age 21.5 years) were included, totaling 5,148 player exposures from 2017 to 2019. In total, 106 ankles presented with radiographic findings (98.15%). The most prevalent radiographic finding was pes planus (47.22%), followed by degenerative joint disease (DJD; 33.33%), talonavicular sclerosis (28.70%), prominent stieda process (25.93%), os trigonum (20.93%), os subfibulare (11.11%), pes cavus (5.56%), subtalar coalition (2.78%), and cavovarus (0.93%). Height ≥80 inches was significantly associated with talonavicular sclerosis and Kellgren-Lawrence 1 changes. Conclusions: This study showed a strong association between height and talonavicular sclerosis and DJD, as well as a relatively high prevalence of pes planus and DJD in asymptomatic collegiate and professional basketball players. Level of Evidence: Level II; Cross-sectional study.

Background Patients on dialysis are commonly prescribed multiple medications (polypharmacy), many of which are potentially inappropriate medications (PIMs). PIMs are associated with an increased risk of falls, fractures, and hospitalization. Deprescribing is a promising intervention to reduce PIMs.Methods We previously conducted a prospective controlled trial whereby we provided deprescribing decision support to nephrologists in one of two tertiary care outpatient hemodialysis units in Montreal, Canada. We aimed to collect information on barriers and facilitators to implementing deprescribing decision support with an electronic tool (MedSafer) by conducting semi-structured interviews among the four nephrologists who participated in the intervention arm of the study, between February and April 2023, following completion of the study. The four nephrologists had conducted medication reviews for a total of 68 patients on the intervention unit during the study. Interviews with participating nephrologists were conducted and transcribed by the study lead. Afterwards, data was coded and analyzed thematically with a focus on their perspective on participating in a quality improvement project during their clinical practice. Two graduate students used a combination of deductive (Theoretical Domains Framework) and inductive coding to analyze each transcribed interview in duplicate. Each coder then created a mind map to visually interpret results and derive themes. A senior qualitative researcher oversaw the development of the final common themes from the interviews.Results Four themes were developed: 1) the importance of deprescribing for patients on hemodialysis, 2) barriers to the success of the deprescribing intervention (e.g., the lack of a clinical pharmacist on the unit), 3) resources that were needed during the intervention (e.g., multidisciplinary team members to facilitate medication reconciliation), and 4) resources that facilitated the intervention (e.g., the provision of deprescribing brochures to patients).Conclusions This was the first study to explore the perspectives of nephrologists participating in a quality improvement project on deprescribing for patients on hemodialysis. This study interviewed a limited number of prescribers, which could limit the contextualized understanding and transferability of the nephrologists’ experiences. As a next step, some of the facilitators identified by the nephrologists should be implemented and studied in a larger clinical trial.Trial registration: NCT05585268

Background: Pilates is among the best conservative management strategies for chronic low back pain. However, several variations of Pilates exist. This study aimed to investigate physical measures that would detect immediate changes after a brief session of Clinical Pilates exercises. Changes in self-reported clinical outcomes, pain and function were also evaluated. Methods: A prospective cohort study was conducted. Eighteen young adults with chronic low back pain participated in this study. Participants were assessed for pain and function subjectively, and hip/knee strength and trunk/hip flexibility objectively, followed by a session of Clinical Pilates assessment and exercises. After the exercises, the participants were immediately reassessed for pain, function, strength, and flexibility. Results: Trunk/hip flexibility showed statistically significant changes after exercise, which were measured with the sit-and-reach test (−3.44 cm, 95% CI [−5.10, −1.79], p < 0.001) and the finger-to-floor test (−6.29 cm [−9.51, −3.06], p = 0.001). Statistical significance was not found in detecting strength changes in hip extension, hip abduction, and knee extension. Changes in pain (1.56 points [0.83, 2.28], p < 0.001) and patient-specific functional scale (−1.52 points [−1.93, −1.10], p < 0.001) were also found after exercise. Conclusions: Trunk/hip flexibility measures detected physical changes after Clinical Pilates exercise, as well as self-reported pain and function outcomes, without reducing strength performance.

Introduction: Individuals with esophageal and gastroesophageal junction (GEJ) cancers are at especially high risk of malnutrition. However, most patients with malnutrition do not receive adequate nutritional support. We conducted a single-arm trial to test the implementation of Support Through Remote Observation and Nutrition Guidance (STRONG), a multilevel digital intervention to improve nutritional outcomes for patients with locally advanced esophageal and gastroesophageal junction cancer. Methods: Participants received five nutritional counseling sessions with a dietitian, logged daily food intake through the Fitbit app, and completed five study assessments related to patient malnutrition, nutrition-related symptoms, and quality-of-life outcomes. We assessed the feasibility, acceptability, and usability of STRONG against a priori benchmarks. Results: Participants (N = 17) had a median age of 68 years, and 71 % were male. Feasibility benchmarks were met for participants completing the baseline assessment (94 %), completing four out of five assessments (82 %), and participant retention (85 %). Among participants who only received an oral diet during the study period, adherence to dietetic appointments (89 %) and food intake tracking (78 %) were high. Participant recruitment rate (47 %) was slightly below the benchmark (50 %). All participants found the intervention to be acceptable. Usability of the intervention was high, with 69 % and 92 % of participants reporting high satisfaction with tracking food intake through the Fitbit and the dietitian-led nutrition counseling sessions, respectively. Conclusion: Our study demonstrated that STRONG could be implemented with high feasibility, acceptability, and usability for esophageal and GEJ cancer patients. Findings from this study can guide a future efficacy study to assess the impact of STRONG on patient outcomes. Clinical trial registration: The Support Through Remote Observation and Nutrition Guidance Program for Gastroesophageal Cancer Patients (STRONG-GEC) study was registered on clinicaltrials.gov (NCT05438940) in June 2022 prior to participant enrollment.

While renal cell carcinoma (RCC) is often linked to smoking, obesity, and hypertension, hereditary forms also account for about 3% of RCC cases. Notably, NCCN guidelines identify 7 major hereditary syndromes associated with an increased RCC risk. Inherited mutations in DNA repair genes, such as ATM, BRCA, and TP53, significantly increase the risk of various cancers. Biallelic pathogenic mutations in ATM cause Ataxia-Telangiectasia (A-T) syndrome, while heterozygous germline pathogenic ATM mutations, present in about 1% of the population, also elevate cancer risk. RCC has not traditionally been associated with germline pathogenic ATM mutations, only limited retrospective analyses have identified such mutations. This case report presents a 68-year-old woman with a germline pathogenic ATM mutation (c.8786+1 G>A) who developed high-risk clear cell RCC followed by an acquired somatic VHL mutation in RCC and a 3-cm serous cystadenoma, illustrating the double-hit phenomenon. Her brother, who shares the same germline pathogenic mutation, was diagnosed with pancreatic cancer and prostate cancer. This case highlights the potential use for enhanced screening protocols for RCC in patients who have germline pathogenic ATM mutations and the importance of research in targeted treatments for tumors driven by dual genetic mechanisms. Increased awareness and vigilant screening for RCC are crucial in managing hereditary cancer syndromes effectively.

BackgroundThe release of ChatGPT (OpenAI) in November 2022 drastically reduced the barrier to using artificial intelligence by allowing a simple web-based text interface to a large language model (LLM). One use case where ChatGPT could be useful is in triaging patients at the site of a disaster using the Simple Triage and Rapid Treatment (START) protocol. However, LLMs experience several common errors including hallucinations (also called confabulations) and prompt dependency. ObjectiveThis study addresses the research problem: “Can ChatGPT adequately triage simulated disaster patients using the START protocol?” by measuring three outcomes: repeatability, reproducibility, and accuracy. MethodsNine prompts were developed by 5 disaster medicine physicians. A Python script queried ChatGPT Version 4 for each prompt combined with 391 validated simulated patient vignettes. Ten repetitions of each combination were performed for a total of 35,190 simulated triages. A reference standard START triage code for each simulated case was assigned by 2 disaster medicine specialists (JMF and MV), with a third specialist (LC) added if the first two did not agree. Results were evaluated using a gage repeatability and reproducibility study (gage R and R). Repeatability was defined as variation due to repeated use of the same prompt. Reproducibility was defined as variation due to the use of different prompts on the same patient vignette. Accuracy was defined as agreement with the reference standard. ResultsAlthough 35,102 (99.7%) queries returned a valid START score, there was considerable variability. Repeatability (use of the same prompt repeatedly) was 14% of the overall variation. Reproducibility (use of different prompts) was 4.1% of the overall variation. The accuracy of ChatGPT for START was 63.9% with a 32.9% overtriage rate and a 3.1% undertriage rate. Accuracy varied by prompt with a maximum of 71.8% and a minimum of 46.7%. ConclusionsThis study indicates that ChatGPT version 4 is insufficient to triage simulated disaster patients via the START protocol. It demonstrated suboptimal repeatability and reproducibility. The overall accuracy of triage was only 63.9%. Health care professionals are advised to exercise caution while using commercial LLMs for vital medical determinations, given that these tools may commonly produce inaccurate data, colloquially referred to as hallucinations or confabulations. Artificial intelligence–guided tools should undergo rigorous statistical evaluation—using methods such as gage R and R—before implementation into clinical settings.

Background Cardiovascular disease (CVD) and cancer frequently co‐occur due to shared risk factors such as obesity, which is linked to CVD and 14 cancer types. This study explores whether CVD pathophysiologies, combined with obesity, increase cancer risk, impacting clinical management. Methods and Results Data from the ARIC (Atherosclerosis Risk in Communities) study, spanning 28 years, were analyzed. The cohort included 5127 participants with incident CVD (myocardial infarction, stroke, heart failure, coronary heart disease), of whom 1511 developed a first primary cancer. Follow‐up began at CVD diagnosis after Visit 1. Obesity was assessed using body mass index, waist circumference, and waist‐to‐hip ratio. Incidence rate differences between obesity groups were adjusted for age, sex, and center, whereas the obesity–cancer association was estimated using Fine‐Gray regression adjusted for shared risk factors including smoking. Cancer incidence in obese individuals with CVD (body mass index: rate differences=226.6/100 000 person‐years) was higher than in those with normal weight. Although obesity was not linked to overall cancer after adjusting for shared risk factors, it was nominally associated with obesity‐related cancers. Specifically, women with CVD and obesity had increased obesity‐related cancer risk (body mass index: hazard ratio, 1.67 [95% CI, 1.17–2.31]). No significant associations were found in men, even after excluding prostate cancer. Conclusions This study suggests that obesity is linked to higher obesity‐related cancer risk in women with incident CVD, independent of shared risk factors. Further research is needed to eliminate residual confounding, understand sex differences, and explore how CVD pathophysiologies and obesity together influence cancer risk.

BackgroundWhile the retail food environment has been well studied, research surrounding the university food environment is still emerging. Existing research suggests that university food environments can influence behavioral outcomes such as students’ dietary choices, which may be maintained long-term. Despite a growing interest in assessing university food environments, there is no standardized tool for completing this task. How researchers define “healthy” when assessing university food environments needs to be clarified. This paper describes the protocol for systematically reviewing literature involving university food environment assessments. ObjectiveThis paper aimed to describe the protocol for a systematic review of the assessments of university food environments. The review will summarize previously used tools or methods and their implications. MethodsElectronic databases, including PubMed (NLM), Cochrane Library (Wiley), Web of Science (Clarivate), APA PsycINFO (EBSCO), CINAHL (Cumulative Index to Nursing & Allied Health) Complete (EBSCO), ProQuest Nursing and Allied Health, and Google Scholar were searched for papers published between 2012 and 2022 using combinations of related medical subject headings terms and keywords. The electronic databases were supplemented by reviewing the reference list for all included papers and systematic reviews returned with our search results. The review will include all study types, including randomized controlled trials, observational studies, and other pre-post designs. Papers that examine at least 1 aspect of the university food environment, such as cafeterias, campus convenience stores, and vending machines, were considered for inclusion. A total of 2 reviewers will independently screen titles and abstracts, complete a full-text review, extract data, and perform a quality assessment of included papers, with a third reviewer resolving any conflicts. The Quality Assessment for Diverse Studies (QuADS) tool was used to determine the methodological quality of selected studies. A narrative and tabular summary of the findings were presented. There will not be a meta-analysis due to the methodological heterogeneity of the included papers. ResultsThe initial queries of 4502 records have been executed, and papers have been screened for inclusion. Data extractions were completed in December 2023. The results of the review were accepted for publication in May 2024. The systematic review generated from this protocol will offer evidence for using different assessment tools to examine the campus food environment. ConclusionsThis systematic review will summarize the tools and methods used to assess university food environments where many emerging adults spend a significant part of their young adult lives. The findings will highlight variations in practice and how “healthy” has been defined globally. This review will provide an understanding of this unique organizational food environment with implications for practice and policy. Trial RegistrationPROSPERO CRD42023398073; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=398073 International Registered Report Identifier (IRRID)DERR1-10.2196/54955

Background: Institutional academic productivity varies on an individual level. This study aims to analyze the research output of adult reconstruction and arthroplasty fellowship programs in the United States. Methods: The American Association of Hip and Knee Surgeons Fellowship Directory was used to evaluate 112 adult reconstruction and arthroplasty fellowships in the United States. Publication data and Hirsch index (h-index) were collected from the Scopus Database. All of each author’s total publications were analyzed with their current institution, regardless of their affiliation at the time of publication. Multivariate logistic regressions were performed to determine the effect of program size on research productivity. Results: The total number of publications per institution ranged from 2 to 3743, with a mean of 289 and a median of 135. The h-index of individual faculty members ranged from 0 to 103, with a mean of 16 and a median of 11. The number of faculty (P < .001) and number of fellows (P = .003) per program had a significant effect on the total number of publications. The number of faculty did not have a significant effect on the median number of publications (P = .12) or the median h-index (P = .31). The number of fellows had a significant effect on the median number of publications (P < .001) and the median h-index (P < .001). Conclusions: Academic productivity in adult reconstruction and arthroplasty fellowships within the United States varies widely, with the top few institutions responsible for a majority of the overall output.

This study aims to determine the relationship between job satisfaction to OCB and organizational commitment partially and simultaneously, by investigating the role of transformational leadership as a moderator variable at CV. Bangun Mandiri. The population of this study were all employees of CV, using testing techniques with the Smart PLS application. This study uses Measurement Model Analysis (Outer Model), Structural Model Analysis (Inner Model), and Hypothesis Testing. The results of this study indicate that Organizational Commitment and Job Satisfaction have no significant effect on OCB. In contrast, Transformational Leadership has a substantial effect on OCB but does not moderate the relationship between Organizational Commitment and Job Satisfaction with OCB. Thus, only Transformational Leadership has a direct impact on increasing OCB without strengthening other relationships.

ABSTRAK Pengguna smartphone pada tahun 2022 sebanyak 6.567 juta pengguna dan akan terus bertambah. Smartphone memiliki banyak fungsi dalam kehidupan sehari-hari seperti mengirim pesan secara instan, berbagi informasi, sebagai media hiburan, mencari teman dan media untuk berjualan. Kemajuan teknologi yang semakin canggih menyebabkan kata tradisional dari mulut ke mulut (WOM) telah ketinggalan zaman dan berubah menjadi kata elektronik dari mulut ke mulut (eWOM). Tujuan penelitian ini yaitu menganalisis pengaruh karakteristik informasi EWOM dan perilaku konsumern terhadap niat beli smartphone di kota Batam. Metode yang digunakan dalam penelitian ini ialah metode kualitatif. Pengumpulan melalui kuesioner dengan kriterianya yaitu generasi Z dengan rentang usia 10-25 tahun yang menggunakan media sosial twitter, instagram, facebook, tiktok, dan youtube. Pada pesebaran kuesioner terdapat 22 pertanyaan sehingga jumlah sample yang dapat digunakan adalah 220 sample dengan rasio 1:10. Selanjutnya, data dianalisis menggunakan PLS-SEM. Hasil penelitian menunjukkan bahwa information quality, information credibility tidak berpengaruh signifikan terhadap purchase intention, sedangkan information usefulness berpengaruh signifikan terhadap purchase intention. Kata Kunci: Smartphone, E-WOM, Purchase Intention ABSTRACT Smartphone users in 2022 will be 6,567 million users and will continue to grow. Smartphones have many functions in everyday life such as sending instant messages, sharing information, as a medium for entertainment, finding friends and a medium for selling. Increasingly sophisticated technological advances have caused traditional word of mouth (WOM) to become outdated and change to electronic word of mouth (eWOM). The aim of this research is to analyze the influence of EWOM information characteristics and consumer behavior on smartphone purchase intentions in the city of Batam. The method used in this research is a qualitative method. Collection via questionnaire with the criteria being generation Z with an age range of 10-25 years who use social media Twitter, Instagram, Facebook, TikTok and YouTube. In distributing the questionnaire there were 22 questions so that the number of samples that could be used was 220 samples with a ratio of 1:10. Next, the data was analyzed using PLS-SEM. The research results show that information quality, information credibility do not have a significant effect on purchase intention, while information usefulness has a significant effect on purchase intention. Keywords: Smartphone, E-WOM, Purchase Intention

Abstract Using smartphone-based ecological momentary assessment, this study investigated an association between natural diversity on mental wellbeing. A sample of 1,998 participants completed 41,448 assessments between April 2018 and September 2023. Environments which included a larger range of natural features, such as trees, plants and birdlife (high natural diversity) were associated with greater mental wellbeing than environments including a smaller range of natural features (low natural diversity). There was evidence of a mediating effect of natural diversity on the association between natural environments and mental wellbeing. These results highlight the importance of policies and practices that support richness of biodiversity for public mental health.

Abstract Prostate cancer pathology plays a crucial role in clinical management but is time-consuming. Artificial intelligence (AI) shows promise in detecting prostate cancer and grading patterns. We tested an AI-based digital twin of a pathologist, vPatho, on 2603 histological images of prostate tissue stained with hematoxylin and eosin. We analyzed various factors influencing tumor grade discordance between the vPatho system and six human pathologists. Our results demonstrated that vPatho achieved comparable performance in prostate cancer detection and tumor volume estimation, as reported in the literature. The concordance levels between vPatho and human pathologists were examined. Notably, moderate to substantial agreement was observed in identifying complementary histological features such as ductal, cribriform, nerve, blood vessel, and lymphocyte infiltration. However, concordance in tumor grading decreased when applied to prostatectomy specimens (κ = 0.44) compared to biopsy cores (κ = 0.70). Adjusting the decision threshold for the secondary Gleason pattern from 5 to 10% improved the concordance level between pathologists and vPatho for tumor grading on prostatectomy specimens (κ from 0.44 to 0.64). Potential causes of grade discordance included the vertical extent of tumors toward the prostate boundary and the proportions of slides with prostate cancer. Gleason pattern 4 was particularly associated with this population. Notably, the grade according to vPatho was not specific to any of the six pathologists involved in routine clinical grading. In conclusion, our study highlights the potential utility of AI in developing a digital twin for a pathologist. This approach can help uncover limitations in AI adoption and the practical application of the current grading system for prostate cancer pathology.

The aim of this study is to determine the effect of an etching material which is the compound of nitric acid-hydrofluoric acid as a pretreatment agent on the shear bond strength of resin cement to two different types of zirconia and comparing it with air particle abrasion. 52 CAD/CAM Zirconia disks were prepared into 3D cubes of 8×8mm and thickness of 3mm. 26 of them were fabricated from high translucent white zirconia ‘group I’ and the other 26 from natural 3D multilayer monolithic zirconia ‘group II’. Each group is then divided into subgroup A and subgroup B according to the surface treatment. All Zirconia cubes were bounded to resin cubes 6x6 mm. 13 of the cubes in subgroup A were treated with the etching material (the test group) and the other 13 in subgroup B were treated with air abrasion (control group). All samples were subjected to thermocycling. Shear bond strength and failure mode were evaluated. The data was collected, tabulated and statistically analyzed using Statistical Package for Social Sciences (SPSS) version 26. The results of the independents samples t-test revealed that there is a statistically significant difference between the shear bond strength in Etched and Air Abrasion in the High Translucent White Zirconia and that there is a statistically significant difference between the shear bond strength of etched and air abrasion in the 3D Multilayered Zirconia. However, there was no statistically significant difference between the shear bond strength among the two types of zirconia after air abrasion and after etching. Regarding the failure mode, it was revealed that most of the specimens that were etched in both types of zirconia have cohesive failure, while the majority of the specimens after air abrasion in both types of zirconia have adhesive failure. Zircos-E etching solution significantly improved bonding to zirconia, increasing shear bond strength with resin cement. Air abrasion on zirconia types resulted in low shear bond strength, indicating a weaker surface treatment compared to Zircos-E etching solution..

The learning environment is an important component in determining the quality and success of the nursing education curriculum. A learning environment that is not supportive can result in decreased student learning performance, including decreased interest and motivation, anxiety and stress, and reduced self-confidence. Evaluation of the learning environment helps improve the quality of the learning environment which consists of the learning process, teaching staff, academic achievement, learning atmosphere, and social environment. This research aims to identify a description of the learning environment for students in the Padjadjaran University nursing professional study program. This research design will use a quantitative descriptive research design. The sampling technique that will be used is proportionate stratified random sampling with 142 nursing professional students as samples. The instrument used is the Dundee Ready Education Environment Measure (DREEM) with 50 statement items. The data analysis that will be carried out is univariate analysis. The results of research on the learning environment dimension show an average score of 148.96/200 in the good category. The average is obtained for each sub-variable; learning process (35.44/48), teaching staff (33.74/44), academic achievement (25.44/32), learning atmosphere (34.49/48), and social environment (19.82/28). Academic achievement with the highest score and social environment with the lowest score. The assessment of the learning environment for nursing professional students shows the Good category, which means that the learning environment for the nursing profession is running well, although there are things that need to be improved and corrected to improve the quality of learning.

Introduction Global surveillance of physical activity (PA) of children and adolescents with questionnaires is limited by the use of instruments developed in high-income countries (HICs) lacking sociocultural adaptation, especially in low- and middle-income countries (LMICs); under-representation of some PA domains; and omission of active play, an important source of PA. Addressing these limitations would help improve international comparisons, and facilitate the cross-fertilisation of ideas to promote PA. We aim to develop and assess the reliability and validity of the app-based Global Adolescent and Child Physical Activity Questionnaire (GAC-PAQ) among 8–17 years old in 14 LMICs and HICs representing all continents; and generate the ‘first available data’ on active play in most participating countries.Methods and analysis Our study involves eight stages: (1) systematic review of psychometric properties of existing PA questionnaires for children and adolescents; (2) development of the GAC-PAQ (first version); (3) content validity assessment with global experts; (4) cognitive interviews with children/adolescents and parents in all 14 countries; (5) development of a revised GAC-PAQ; (6) development and adaptation of the questionnaire app (application); (7) pilot-test of the app-based GAC-PAQ; and, (8) main study with a stratified, sex-balanced and urban/rural-balanced sample of 500 children/adolescents and one of their parents/guardians per country. Participants will complete the GAC-PAQ twice to assess 1-week test–retest reliability and wear an ActiGraph wGT3X-BT accelerometer for 9 days to test concurrent validity. To assess convergent validity, subsamples (50 adolescents/country) will simultaneously complete the PA module from existing international surveys.Ethics and dissemination Approvals from research ethics boards and relevant organisations will be obtained in all participating countries. We anticipate that the GAC-PAQ will facilitate global surveillance of PA in children/adolescents. Our project includes a robust knowledge translation strategy sensitive to social determinants of health to inform inclusive surveillance and PA interventions globally.

Rationale & Objective: Patients treated with dialysis are commonly prescribed multiple medications (polypharmacy), including some potentially inappropriate medications (PIMs). PIMs are associated with an increased risk of medication harm (eg, falls, fractures, hospitalization). Deprescribing is a solution that proposes to stop, reduce, or switch medications to a safer alternative. Although deprescribing pairs well with routine medication reviews, it can be complex and time-consuming. Whether clinical decision support improves the process and increases deprescribing for patients treated with dialysis is unknown. This study aimed to test the efficacy of the clinical decision support software MedSafer at increasing deprescribing for patients treated with dialysis. Study Design: Prospective controlled quality improvement study with a contemporaneous control. Setting & Participants: Patients prescribed ≥5 medications in 2 outpatient dialysis units in Montréal, Canada. Exposures: Patient health data from the electronic medical record were input into the MedSafer web-based portal to generate reports listing candidate PIMs for deprescribing. At the time of a planned biannual medication review (usual care), treating nephrologists in the intervention unit additionally received deprescribing reports, and patients received EMPOWER brochures containing safety information on PIMs they were prescribed. In the control unit, patients received usual care alone. Analytical Approach: The proportion of patients with ≥1 PIMs deprescribed was compared between the intervention and control units following a planned medication review to determine the effect of using MedSafer. The absolute risk difference with 95% CI and number needed to treat were calculated. Outcomes: The primary outcome was the proportion of patients with one or more PIMs deprescribed. Secondary outcomes include the reduction in the mean number of prescribed drugs and PIMs from baseline. Results: In total, 195 patients were included (127, control unit; 68, intervention unit); the mean age was 64.8 ± 15.9 (SD), and 36.9% were women. The proportion of patients with ≥1 PIMs deprescribed in the control unit was 3.1% (4/127) vs 39.7% (27/68) in the intervention unit (absolute risk difference, 36.6%; 95% CI, 24.5%-48.6%; P

Extracellular vesicles mediate intercellular communication by transporting biologically active macromolecules. Our prior studies have demonstrated that the nuclear factor of activated T cell cytoplasmic member 3 (NFATc3) is activated in mouse pulmonary macrophages in response to lipopolysaccharide (LPS). Inhibition of NFATc3 activation by a novel cell-permeable calcineurin peptide inhibitor CNI103 mitigated the development of acute lung injury (ALI) in LPS-treated mice. Although pro-inflammatory lipid mediators are known contributors to lung inflammation and injury, it remains unclear whether the calcineurin-NFATc pathway regulates extracellular vesicle (EV) lipid content and if this content contributes to ALI pathogenesis. In this study, EVs from mouse bronchoalveolar lavage fluid (BALF) were analyzed for their lipid mediators by liquid chromatography in conjunction with mass spectrometry (LC-MS/MS). Our data demonstrate that EVs from LPS-treated mice contained significantly higher levels of arachidonic acid (AA) metabolites, which were found in low levels by prior treatment with CNI103. The catalytic activity of lung tissue cytoplasmic phospholipase A2 (cPLA2) increased during ALI, correlating with an increased amount of arachidonic acid (AA) in the EVs. Furthermore, ALI is associated with increased expression of cPLA2, cyclooxygenase 2 (COX2), and lipoxygenases (5-LOX, 12-LOX, and 15-LOX) in lung tissue, and pretreatment with CNI103 inhibited the catalytic activity of cPLA2 and the expression of cPLA2, COX, and LOX transcripts. Furthermore, co-culture of mouse pulmonary microvascular endothelial cell (PMVEC) monolayer and NFAT-luciferase reporter macrophages with BALF EVs from LPS-treated mice increased the pulmonary microvascular endothelial cell (PMVEC) monolayer barrier permeability and luciferase activity in macrophages. However, EVs from CNI103-treated mice had no negative impact on PMVEC monolayer barrier integrity. In summary, BALF EVs from LPS-treated mice carry biologically active NFATc-dependent, AA-derived lipids that play a role in regulating PMVEC monolayer barrier function.

While enhancing our economic relations with African countries was positioned as a target within Türkiye's vision, especially after the Cold War, this could only come true in the first decade of the 21st century. As a result, there have been significant developments in the volume of trade. Although Türkiye had a trade deficit with Africa from the mid-90s to the early 2000s, due to stagnation and the impacts of various crises, it became a surplus party in the subsequent period. The trade with Africa is primarily with North African countries due to geographical proximity and historical ties. While Africa's share in Türkiye's total foreign trade volume has been gradually increasing, it remains significantly lower compared to Asia and Europe. Relations between the continent and Türkiye haven't grown stronger yet, largely because the majority of African countries were former colonies. In African countries, which were primarily former colonies of European nations, customs duties and non-tariff barriers are applied to Non-european countries. On the other hand, Türkiye's geographical proximity to Africa offers a significant opportunity to meet the agricultural and food needs of African countries. In this context, the aim of this study is to analyze Türkiye's trade with the African continent and to reveal the opportunities, threats, strengths, and weaknesses this trade offers for both actors. Furthermore, the study provides recommendations to enhance these relations in this framework.

Abstract Heterozygous SNVs or CNV deletions involving the FOXF1 gene, or its distant enhancer, are causative for 80–90% of cases of alveolar capillary dysplasia with misalignment of pulmonary veins. Recently, we proposed bimodal structure and parental functional dimorphism of the lung-specific FOXF1 enhancer, with Unit 1 having higher activity on the paternal chr16 and Unit 2 on the maternal chr16. Here, we describe a novel unusually sized pathogenic de novo copy-number variant deletion involving a portion of the FOXF1 enhancer on maternal chr16 that implies narrowing Unit 2 to an essential ~ 9-kb segment. Using a restrictase-based assay, we found that this enhancer segment is weakly methylated at ApT adenine, with about twice the frequency of methylation on the maternal versus paternal chr16. Our data provide further insight into the FOXF1 enhancer structure and function.

Background: Malnutrition is a common and distressing condition among pancreatic cancer patients. Fewer than a quarter of pancreatic cancer patients receive medical nutrition therapy (MNT), important for improving nutritional status, weight maintenance, quality of life and survival. System, provider, and patient level barriers limit access to MNT. We propose to examine the feasibility of a 12-week multi-level, digital health intervention designed to expand MNT access among pancreatic cancer patients. Methods: Individuals with advanced pancreatic cancer starting chemotherapy (N = 80) will be 1:1 randomized to the intervention or usual care. The Support Through Remote Observation and Nutrition Guidance (STRONG) intervention includes system-level (e.g., routine malnutrition and screening), provider-level (e.g., dietitian training and web-based dashboard), and patient-level strategies (e.g., individualized nutrition plan, self-monitoring of dietary intake via Fitbit, ongoing goal monitoring and feedback). Individuals receiving usual care will be referred to dietitians based on their oncologists’ discretion. Study assessments will be completed at baseline, 4-, 8-, 12-, and 16-weeks. Results: Primary outcomes will be feasibility (e.g., recruitment, retention, assessment completion) and acceptability. We will collect additional implementation outcomes, such as intervention adherence, perceived usability, and feedback on intervention quality via an exit interview. We will collect preliminary data on outcomes that may be associated with the intervention including malnutrition, quality of life, treatment outcomes, and survival. Conclusion: This study will advance our knowledge on the feasibility of a digital health intervention to reduce malnutrition among individuals with advanced pancreatic cancer. Trial registration: NCT05675059, registered on December 9, 2022.

IntroductionHairy vetch (Vicia villosa Roth) is a promising legume cover crop, but its use is limited by high rates of pod dehiscence and seed dormancy.MethodsWe used phenotypically contrasting pooled DNA samples (n=24 with 29-74 individuals per sample) from an ongoing cover crop breeding program across four environments (site-year combinations: Maryland 2020, Maryland 2022, Wisconsin 2021, Wisconsin 2022) to find genetic associations and genomic prediction accuracies for pod dehiscence and seed dormancy. We also combined pooled DNA sample genetic association results with the results of a prior genome-wide association study.Results and discussionGenomic prediction resulted in positive predictive abilities for both traits between environments and with an independent dataset (0.34-0.50), but reduced predictive ability for DNA pools with divergent seed dormancy in the Maryland environments (0.07-0.15). The pooled DNA samples found six significant (false discovery rate q-value

Candidemia is the most common form of invasive fungal infection associated with several risk factors, and one of them is the use of medical devices, to which microbial biofilms can attach. Candidemia related to the use of peripheral intravascular and central venous catheters (CVC) is referred to as Candida catheter-related bloodstream infection, with more than 90% being related to CVC usage. The infection is associated with a higher morbidity and mortality rate than nosocomial bacterial infections. Candida spp. can protect themselves from the host immune system and antifungal drugs because of the biofilm structure, which is potentiated by the extracellular matrix (ECM). Candida albicans and Candida parapsilosis are the most pathogenic species often found to form biofilms associated with catheter usage. Biofilm formation of C. albicans includes four mechanisms: attachment, morphogenesis, maturation and dispersion. The biofilms formed between C. albicans and non-albicans spp. differ in ECM structure and composition and are associated with the persistence of colonization to infection for various catheter materials and antifungal resistance. Efforts to combat Candida spp. biofilm formation on catheters are still challenging because not all patients, especially those who are critically ill, can be recommended for catheter removal; also to be considered are the characteristics of the biofilm itself, which readily colonizes the permanent medical devices used. The limited choice and increasing systemic antifungal resistance also make treating it more difficult. Hence, alternative strategies have been developed to manage Candida biofilm. Current options for prevention or therapy in combination with systemic antifungal medications include lock therapy, catheter coating, natural peptide products and photodynamic inactivation.

Modern conservative dentistry is taking the lead in daily clinical practice and is relying on adhesion. Whether it is a simple composite, ceramic inlays, onlays, veneers or crowns, the common factor for a successful outcome is a good bonding of these elements to dental structures. Thus, the purpose of this study was to evaluate the bond strength of resin composite to dentin when using a new device, the DENTIPURE KM™ (KM, Beirut, Lebanon), which provides a pure air flow, free of any contaminants and without humidity, when compared to other dental equipment. One hundred and eighty extracted human molars were equally divided into three groups according to the device used, the DENTIPURE KM™ (KM, Beirut, Lebanon), the KAVO™ (ESTETICA E30/E70/E80 Vision, KAVO, Biberach, Germany), or the ADEC™ (A-dec Performer 200, Newberg, OR, USA). The shear bond strength (SBS) was evaluated after 24 h of storage in distilled water on a universal testing machine. Statistical analysis was set with a level of significance at p ≤ 0.05. The results revealed that significantly different bond strength was imparted by the DENTIPURE KM™ device and the ADEC™ dental unit (p = 0.042). In conclusion, while the DENTIPURE KM™ device shows promise in providing contaminant-free air during bonding, its impact on dentin bond strength compared to devices like the KAVO™ appears minimal. Further research is needed to fully assess its potential in enhancing dentinal adhesion procedures.

Objective To explore and model factors affecting antibiotic prescribing decision-making early in the pandemic.Design Semistructured qualitative interview study.Setting National Health Service (NHS) trusts/health boards in England and Wales.Participants Clinicians from NHS trusts/health boards in England and Wales.Method Individual semistructured interviews were conducted with clinicians in six NHS trusts/health boards in England and Wales as part of the Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients study, a wider study that included statistical analysis of procalcitonin (PCT) use in hospitals during the first wave of the pandemic. Thematic analysis was used to identify key factors influencing antibiotic prescribing decisions for patients with COVID-19 pneumonia during the first wave of the pandemic (March to May 2020), including how much influence PCT test results had on these decisions.Results During the first wave of the pandemic, recommendations to prescribe antibiotics for patients with COVID-19 pneumonia were based on concerns about secondary bacterial infections. However, as clinicians gained more experience with COVID-19, they reported increasing confidence in their ability to distinguish between symptoms and signs caused by SARS-CoV-2 viral infection alone, and secondary bacterial infections. Antibiotic prescribing decisions were influenced by factors such as clinician experience, confidence, senior support, situational factors and organisational influences. A decision-making model was developed.Conclusion This study provides insight into the decision-making process around antibiotic prescribing for patients with COVID-19 pneumonia during the first wave of the pandemic. The importance of clinician experience and of senior review of decisions as factors in optimising antibiotic stewardship is highlighted. In addition, situational and organisational factors were identified that could be optimised. The model presented in the study can be used as a tool to aid understanding of the complexity of the decision-making process around antibiotic prescribing and planning antimicrobial stewardship support in the context of a pandemic.Trial registration number ISRCTN66682918.

PurposeIntensity-modulated radiation therapy (IMRT) with brachytherapy boost for unfavorable prostate cancer has been shown to improve biochemical relapse-free survival compared to IMRT alone. Stereotactic body radiation therapy (SBRT) is a less-invasive alternative to brachytherapy. Early outcomes utilizing SBRT boost suggest low rates of high-grade toxicity with a maintained patient-reported quality of life. Here, we report the 5-year progression-free survival (PFS) and prostate cancer-specific survival (PCSS) of patients treated with IMRT plus SBRT boost.Materials and methodsBetween 2008 and 2020, 255 patients with unfavorable prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45–50.4 Gy) according to an institutional protocol. For the first year, the patient’s PSA level was monitored every 3 months, biannually for 2 years, and annually thereafter. Failure was defined as nadir + 2 ng/mL or a rising PSA with imaging suggestive of recurrence. Detection of recurrence also included digital rectal examination and imaging studies, such as MRI, CT, PET/CT, and/or bone scans. PFS and PCSS were calculated using the Kaplan–Meier method.ResultsThe median follow-up period was 71 months. According to the NCCN risk classification, 5% (13/255) of the patients had favorable intermediate-risk disease, 23% (57/255) had unfavorable intermediate-risk disease, 40% (102/255) had high-risk disease, and 32% (83/255) had very high-risk disease. Androgen deprivation therapy was administered to 80% (204/255) of the patients. Elective pelvic lymph node IMRT was performed in 28 (10%) patients. The PFS for all patients at 5 years was 81% (favorable intermediate risk, 91%; unfavorable intermediate risk, 89%; high-risk, 78%; and very-high risk, 72%). The PCSS for all patients at 5 years was 97% (favorable intermediate risk, 100%; unfavorable intermediate risk, 100%; high risk, 100%; and very high risk, 89%).ConclusionThe incidence of failure following IMRT plus SBRT for unfavorable prostate cancer remains low at 5 years.

Lettuce drop caused by Sclerotinia minor is a damaging disease of romaine lettuce (Lactuca sativa L.) production in California. Introgression of partial resistance from wild, primitive, or heirloom accessions into modern cultivars could improve integrated management approaches to the disease. Breeding methods for lettuce drop resistance are not well developed and hinder the development of new lettuce drop–resistant cultivars. The objective of this work was to develop a pedigree-based breeding method for introgression of lettuce drop resistance into modern romaine germplasm. Progeny from crosses between the partially resistant cultivar Eruption and the susceptible romaine cultivars Darkland and Hearts Delight were selected in a modified pedigree breeding scheme. Families were evaluated for disease incidence and selected for lettuce drop resistance in artificially infested field experiments conducted in the summer and fall. Infected plants of partially resistant lines commonly do not produce seed, and therefore selection of resistant plants from infested nurseries is not possible. Noninfested field experiments were used to select individual plants with improved horticultural characteristics for seed production, but from within resistant families only. Evaluation and selection of progeny using this breeding scheme occurred from the F2:3 through the F5:6 generations. In all generations, superior resistance was identified in the ‘Eruption’ × romaine crosses. The breeding scheme generated eight green romaine-type inbred lines with better resistance than the romaine parent and better head weight than ‘Eruption’. Use of the new romaine lines as parents in backcrosses to romaine produced F2:3 families with high levels of resistance. The pedigree method used in this research can be implemented with any source of resistance, but is constrained by the use of family selection and the inability to select individual plants for resistance directly. Breeding schemes that use single seed descent or molecular markers are alternative approaches that would enable selection for resistance on individual genotypes.

Student satisfaction is an important factor in the success of full online learning during the Covid-19 pandemic. A low level of learning satisfaction will have an impact on student academic achievement. This study aims to describe the level of student satisfaction who participated in online learning at the Faculty of Nursing, Universitas Padjadjaran (Unpad) during the Covid-19 pandemic. This study used a quantitative descriptive design. The study population was undergraduate nursing students at the Unpad (N=855). The sampling technique uses proportionate stratified random sampling (n=276). The research instrument used a questionnaire created by Al Musharraf and Khayra. All data were analyzed using descriptive univariate, and presented in the form of a frequency distribution table. The results showed that the level of student satisfaction with online learning was 139 respondents (50.4%) in the low category, and 137 respondents (49.6%) in the high category. According to the subdomain, more than half of the respondents (50.4%) had a high level of satisfaction with the online learning environment, more than half reported that satisfaction with university support during Covid-19 and student satisfaction with online learning platforms and methods were in the low category (59, 1% and 53.6%, respectively). In conclusion, some students have a low level of satisfaction with online learning. Student satisfaction with online learning can be increased by paying attention to each dimension of satisfaction, namely the learning environment, institutional and platform support and online learning designs. Kepuasan mahasiswa merupakan faktor penting dalam keberhasilan pembelajaran daring. Tingkat kepuasan belajar yang rendah akan berdampak pada prestasi akademik mahasiswa. Salah satu permasalahan dalam pembelajaran daring adalah kepuasan yang mengakibatkan proses penyesuaian diri menjadi lemah sehingga berdampak pada minat dan motivasi mahasiswa saat belajar. Penelitian ini bertujuan untuk menggambarkan tingkat kepuasan mahasiswa dalam pembelajaran daring pada mahasiswa Fakultas Keperawatan Universitas Padjadjaran pada masa pandemic Covid 19. Penelitian ini menggunakan desain deskriptif kuantitatif. Populasi penelitian adalah Mahasiswa aktif Fakultas Keperawatan Unpad (N=855). Teknik sampling menggunakan proportionate stratified random sampling (n=276). Instrumen yang digunakan dalam penelitian ini adalah kuesioner yang dibuat oleh Almusharraf dan Khahro. Seluruh data dianalisis dengan menggunakan deskriptif univariat dan disajikan dalam bentuk tabel distribusi frekuensi. Hasil penelitian yang dilakukan didapatkan bahwa secara umum keduanya hampir sama dengan tingkat kepuasan dalam pembelajaran daring dalam kategori rendah sebanyak 139 responden (50,4%) sedangkan sebanyak 137 responden (49,6%) mahasiswa dalam kategori tinggi. Mahasiswa memiliki tingkat Kepuasan Lingkungan pembelajaran daring tinggi 137 responden (50,4%), Kepuasan dukungan Universitas selama Covid 19 rendah 163 responden (59,1%) dan Kepuasan siswa terhadap platform dan metode pembelajaran daring yang rendah 148 responden (53,6%). Kesimpulannya, seluruh mahasiswa memiliki tingkat kepuasan pada pembelajaran daring yang hampir sama. Dukungan melalui diskusi antar responden, dosen dan media pembelajaran disarankan untuk dimaksimalkan baik oleh kampus maupun dosen

Abstract The potential of the metaverse in the field of education is an area of increasing interest, with many researchers exploring the space to increase the ease and efficacy of student education while reducing time and labor requirements to deliver effective teaching. However, there has been little work into the systematic and technological aspects of delivering education through the metaverse. To fill this gap, we propose a metaverse education system that takes good advantages of virtual reality and Web3 blockchain techologies to create a social learning environment. With this added emphasis on social aspects, learners are able to socialize and engage in collaborative efforts to improve their own knowledge. Using blockchain technology, the system can also help to ensure security and transparency while also keeping progression and grading fair for all participating students.

High-affinity antibodies are often identified through directed evolution but deep leaning methods hold great promise. Here the authors report RESP, a pipeline for efficient identification of high affinity antibodies, and apply this to the PD-L1 antibody Atezolizumab.

Background: Telerobotic surgery could improve access to specialty procedures such as cardiac catheter ablation in rural and underserved regions in the United States and worldwide. Advancements in telecommunications, internet infrastructure, and surgical robotics are lowering the technical hurdles for this future healthcare delivery paradigm. Nonetheless, important questions remain regarding the safe implementation of telerobotic surgery in rural community hospital settings. Objective: The purpose of this study was to pilot test a system and methods to explore telerobotic cardiac catheter ablation in a rural community hospital setting. Methods: We assembled a portable preclinical telerobotic catheter ablation system from commercial-grade components using third-party vendors. We then carried out 4 telerobotic surgery simulations with an urban surgeon and a rural community hospital operating room (OR) team spanning a distance of more than 2000 miles. Two challenge scenarios were incorporated into the simulations, including loss of network connection and cardiac perforation with subsequent life-threatening tamponade physiology. An ethnographic analysis was then performed. Results: Interviews and observations suggested that rural OR teams readily adapt to the telesurgery context. However, participant perceptions of team trust, communication, and emergency management were significantly altered by the remote location of the surgeon. In addition, most participants believed the OR team would have been better equipped for the challenges had they received formal training or had prior experience with the procedure being simulated. Conclusion: We demonstrate the utility and feasibility of a system and methods for studying specialty telerobotic surgery in a rural hospital OR setting.

Fabrication errors limit the scaling of programmable photonic circuits. Here the authors show how a broad class of circuits can be made asymptotically fault-tolerant, where the effect of errors remains controlled regardless of the circuit’s size.

Abstract Background A significant portion of diabetic macular edema (DME) is refractory to anti-vascular endothelial growth factor (anti-VEGF) agents. This study investigates morphological and functional outcomes to a single intravitreal bevacizumab (IVB) injection in patients with center-involving DME (ciDME) at 4–6 weeks and compares treatment responders and non-responders based on spectral domain optical coherence tomography (SD-OCT) features. Methods IRB approved observational, retrospective chart review of patients with ciDME, identified by ICD-10 code, who received IVB and underwent baseline and 4–6 weeks follow-up SD-OCT imaging between January 1, 2016 and January 19, 2021. Patients who had received previous treatment with anti-VEGF or intraocular steroids within 1 year were excluded. Variables included best-corrected visual acuity (BCVA), central subfield thickness (CST) and total macular volume (TMV). Eyes were classified as responders if CST reduction was greater than 10%. OCT scans were graded qualitatively by two masked graders using Imagivault software. Paired Student’s t-tests, Wilcoxon signed rank tests and Chi-Square tests were used for analysis. Results A total of 334 prospective subjects were identified, and after applying exclusion criteria 52 eyes from 46 patients (mean age 64.22 ± 8.12 years, 58.7% male) were included. Mean BCVA did not significantly change with treatment, 63.9 ETDRS letters (~ 20/50) at baseline and 65.9 ETDRS letters (~ 20/50) post-treatment (p = 0.07). Mean CST decreased from 466 ± 123 μm at baseline to 402 ± 86 μm post-treatment (p

Hairy vetch (Vicia villosa Roth), a winter-hardy annual legume, is a promising cover crop. To fully leverage its potential, seed production and field performance of V. villosa must be improved to facilitate producer adoption. Two classic domestication traits, seed dormancy (hard seed) and dehiscence (pod shatter), are selection targets in an ongoing breeding program. This study reports a genome-wide association study of 1,019 V. villosa individuals evaluated at two sites (Knox City, Texas and Corvallis, Oregon) for the proportion of dormant seed, visual pod dehiscence scores, and two dehiscence surrogate measures (force to dehiscence and pod spiraling score). Trait performance varied between sites, but reliability (related to heritability) across sites was strong (dormant seed proportion: 0.68; dehiscence score: 0.61; spiraling score: 0.42; force to dehiscence: 0.41). A major locus controlling seed dormancy was found (q-value: 1.29 × 10−5; chromosome 1: position: 63611165), which can be used by breeding programs to rapidly reduce dormancy in breeding populations. No significant dehiscence score QTL was found, primarily due to the high dehiscence rates in Corvallis, Oregon. Since Oregon is a potentially major V. villosa seed production region, further dehiscence resistance screening is necessary

Hemophilia is a bleeding disorder caused by a single absent/defective gene and characterized by a lack of functional clotting factors. People with hemophilia may experience joint damage, pain, and psychological impairments, all of which could contribute to reduced health-related quality of life (HRQoL). The current standard of care is clotting factor replacement, which is associated with regular infusions; therefore, alternative treatments such as gene therapy (GT) are in development. GT involves the delivery of a functional copy of the clotting factor 8/9 gene by a single infusion into the patient's cells, enabling them to produce their own clotting factor VIII/IX. The impact of treatment on patients’ HRQoL can be assessed using hemophilia-specific patient-reported outcome (PRO) measures. Since these measures were designed before the advent of GT, there is a need for updated individualized PRO measures. Patient groups and regulatory authorities emphasize the need for increased patient engagement when considering clinical trial design. Here, we provide patients’ perspective on undergoing GT and discuss how to capture the patient voice when measuring the therapy's transformative impact.

Pancreatic islets are three-dimensional cell aggregates consisting of unique cellular composition, cell-to-cell contacts, and interactions with blood vessels. Cell aggregation is essential for islet endocrine function; however, it remains unclear how developing islets establish aggregation. By combining genetic animal models, imaging tools, and gene expression profiling, we demonstrate that islet aggregation is regulated by extracellular matrix signaling and cell-cell adhesion. Islet endocrine cell-specific inactivation of extracellular matrix receptor integrin β1 disrupted blood vessel interactions but promoted cell-cell adhesion and the formation of larger islets. In contrast, ablation of cell-cell adhesion molecule α-catenin promoted blood vessel interactions yet compromised islet clustering. Simultaneous removal of integrin β1 and α-catenin disrupts islet aggregation and the endocrine cell maturation process, demonstrating that establishment of islet aggregates is essential for functional maturation. Our study provides new insights into understanding the fundamental self-organizing mechanism for islet aggregation, architecture, and functional maturation.

We report a simple synthesis process for a wide variety of ultrasmall nanocrystals. Simply immersing a dialysis bag containing an aqueous solution of a metal salt mixed with citric acid in a NaOH solution reservoir for 10 min, nanocrystals measuring only a few nanometers in size are formed inside the dialysis bag. We demonstrated the synthesis of ultrasmall nanocrystals of Co, Ni, Cu, Ag, Au, Pd, Cu2O, FeO, and CeO2, and found that the gradual change in pH caused by the diffusion of OH− ions through the dialysis membrane played an essential role in the formation of these nanocrystals. This method can be readily adapted for almost all transition metal elements, providing researchers in the fields of catalysis and nanomedicine an easy access to a wide range of ultrasmall metal and oxide nanocrystals.

Abstract The mental health benefits of everyday encounters with birdlife for mental health are poorly understood. Previous studies have typically relied on retrospective questionnaires or artificial set-ups with little ecological validity. In the present study, we used the Urban Mind smartphone application to examine the impact of seeing or hearing birds on self-reported mental wellbeing in real-life contexts. A sample of 1292 participants completed a total of 26,856 ecological momentary assessments between April 2018 and October 2021. Everyday encounters with birdlife were associated with time-lasting improvements in mental wellbeing. These improvements were evident not only in healthy people but also in those with a diagnosis of depression, the most common mental illness across the world. These findings have potential implications for both environmental and wildlife protection and mental healthcare policies. Specific measures, aimed at preserving and increasing everyday encounters with birdlife in urban areas, should be implemented.

PCL reconstructive techniques are constantly evolving, and further clinical studies are needed to definitively understand the potential benefits of internal brace augmentation and anatomic double-bundle PCL reconstruction. This Technical Note reports an arthroscopic all-inside anatomic double-bundle PCL reconstruction with internal brace augmentation that is effective and reproducible.

Context: Modified polyether ether ketone (PEEK) by adding nano-hydroxyapatite (HA) material on its fixture for mini-implant fabrication may increase resistance force through osseointegration. Aims: To analyze the binding molecular docking of PEEK incorporated with HA as a biomaterial candidate for orthodontic mini-implant fabrication through a bioinformatic approach, an in silico study. Methods: 3D ligand structure consisting of HA, PEEK and target proteins consisting of osteopontin, osteocalcin, osteonectin, bone morphogenetic protein 4 (BMP4), bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 7 (BMP7), alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), Insulin growth factor-1 (IGF-1), osterix, tartrate-resistant acid phosphatase (TRAP), collagen alpha-1 (COL1A1) obtained from RCSB-PDB. It was analyzed the binding affinity of a single HA, PEEK, and HA + PEEK complex to twelve target proteins related to osseointegration. The types of chemical interactions produced by the ligands in the target protein domain consisted of Van der Waals, hydrogen, hydrophobic, pi, and alkyl. Results: The blind docking simulation succeeded in identifying the most negative binding affinity; it was found in the HA + PEEK molecular complex compared to HA and PEEK in the single condition. The type of chemical interaction formed consisted of hydrogen, van der Waals, pi, and alkyl. HA+PEEK showed the most negative binding affinity with ALP and IGF-1, as much as -8.7 binding affinity. Conclusions: The molecular docking of PEEK with HA exhibited a prominent binding affinity with osteogenic markers like ALP and IGF-1 in silico, allowing it to have a higher potential than nano-HA or PEEK as a single biomaterial for osseointegration as the fabrication of mini-implants that may support orthodontic treatment.