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Purpose To report the potential reduction of carbon emissions by utilising air-tamponade (AT), where possible, instead of fluorinated gases in the management of rhegmatogenous retinal detachment (RRD). We compared the carbon CO2 emissions produced at two large tertiary referral vitreoretinal (VR) centres where RRD are exclusively repaired using fluorinated gases to a tertiary VR mass of each gas used according to the Intergovernmental Panel on Climate Change. Materials and methods Retrospective, continuous, comparative multicentre study of all procedures using fluorinated gases between 01/01/17-31/12/20 at the Manchester Royal Eye Hospital (MREH) and Birmingham and Midland Eye Centre (BMEC), and between 01/01/19-31/12/2020 at the University Hospitals Coventry and Warwickshire (UHCW). Results We report on 3,239 (SF6:1,415 [43.7%], C2F6:1,235 [38.1%], C3F8:541 [16.7%], Air:48 [1.5%]) procedures. UHCW and BMEC utilise single use 30ml and 75ml cannisters, respectively and MREH use multi-use gas cylinders. UHCW used AT in 48 (70%) of RRD repairs. Mean equivalent mass CO2/patient was MREH:115.9kg, BMEC:7.9kg and UHCW:1.9kg. If assuming all centres used 30ml cannisters, the mean equivalent mass CO2/patient was MREH:3.5 kg, BMEC:3.1kg and UHCW:1.9kg. AT enabled UHCW to greatly reduce the need for the most environmentally damaging SF6 gas, leading to lower CO2 emissions by 47.0% and 41.1% compared to MREH and BMEC, respectively. Conclusion We demonstrate how AT vs. the fluorinated gases can reduce in carbon footprint in the management of RRD. Further studies are required to determine the most ‘environment-friendly’ intraocular tamponade without compromising patient outcomes centre that also routinely employs AT in selected RRD cases.

BACKGROUND: 1.8 million Veterans are estimated to need legal services, such as for housing eviction prevention, discharge upgrades, and state and federal Veterans benefits. While having ones legal needs met is known to improve ones health and its social determinants, many Veterans legal needs remain unmet. Public Law 116-315 enacted in 2021 authorizes VA to fund legal services for Veterans (LSV) by awarding grants to legal service providers including nonprofit organizations and law schools legal assistance programs. This congressionally mandated LSV initiative will award grants to about 75 competitively selected entities providing legal services. This paper describes the protocol for evaluating the initiative. The evaluation will fulfill congressional reporting requirements, and inform continued implementation and sustainment of LSV over time. METHODS: Our protocol calls for a prospective, mixed-methods observational study with a repeated measures design, aligning to the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) and Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) frameworks. In 2023, competitively selected legal services-providing organizations will be awarded grants to implement LSV. The primary outcome will be the number of Veterans served by LSV in the 12 months after the awarding of the grant. The evaluation has three Aims. Aim 1 will focus on measuring primary and secondary LSV implementation outcomes aligned to RE-AIM. Aim 2 will apply the mixed quantitative-qualitative Matrixed Multiple Case Study method to identify patterns in implementation barriers, enablers, and other i-PARIHS-aligned factors that relate to observed outcomes. Aim 3 involves a mixed-methods economic evaluation to understand the costs and benefits of LSV implementation. DISCUSSION: The LSV initiative is a new program that VA is implementing to help Veterans who need legal assistance. To optimize ongoing and future implementation of this program, it is important to rigorously evaluate LSVs outcomes, barriers and enablers, and costs and benefits. We have outlined the protocol for such an evaluation, which will lead to recommending strategies and resource allocation for VAs LSV implementation.

Purpose Socio-economic deprivation and ethnic variation have been frequently linked to poorer health outcomes. We collected a large series of primary macula-on rhegmatogenous retinal detachment (RRD) cases and analysed the effect of socio-economic deprivation and ethnicity on both six-month retinal re-detachment rate and visual outcomes. Materials and methods Retrospective consecutive case series of 568 patients attending Birmingham and Midlands Eye Centre from January 2017–2020. Multiple Indices of Deprivation (IMD) deciles were used for deprivation status and split to two groups: IMD-A (Decile 1–5) and IMD-B (Decile 6–10). The two largest subgroups of ethnicities were compared, White and South Asians (SA). Results We report an overall retinal re-detachment rate of 8.5%. IMD-A re-detached significantly more than IMD-B (11.2% vs 6.0% respectively, p = 0.034). No statistical significance was found between White and SA re-detachment rate (9.1% and 5.6% respectively, p = 0.604). SA median age significantly lower at 49 years (IQR: 37–61) compared to White patients at 57 years (IQR: 50–65) (p = Conclusion We demonstrated an increased retinal re-detachment rate in our more deprived patients according to IMD and a younger cohort of SA compared to White ethnicity. Further prospective studies are required to demonstrate the link between socio-economic deprivation and surgical success.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) has garnered interest as a viable alternative to the traditional surgical mitral valve replacement (SMVR) for high-risk patients requiring redo operations. This study aims to evaluate the association of TMVR with selected clinical and financial outcomes. METHODS: Adults undergoing isolated redo mitral valve replacement were identified in the 2016-2020 Nationwide Readmissions Database and categorized into TMVR or SMVR cohorts. Various regression models were developed to assess the association between TMVR and in-hospital mortality, as well as additional secondary outcomes. Transseptal and transapical catheter-based approaches were also compared in relation to study endpoints. RESULTS: Of an estimated 7,725 patients, 2,941 (38.1%) underwent TMVR. During the study period, the proportion of TMVR for redo operations increased from 17.8% to 46.7% (nptrend

PurposeTo assess the effectiveness of Home Fire Safety (HFS) interventions versus other interventions/no interventions/controls on HFS knowledge and behaviour at short-, intermediate- and long-term follow ups.DesignSystematic review and meta-analysis of randomized controlled trials.Data sourcesMEDLINE, EMBASE and PubMed databases were searched from January 1998 to July 2018, and studies retrieved.ParticipantsToddlers, children (primary or secondary school), teenagers or adults.Interventions/comparisonHFS interventions compared to other interventions / no interventions / controls.OutcomesHFS knowledge and behaviour.Results10 studies were identified (8 RCTs and 2 prospective cohort). Two studies assessed the effects of HFS interventions vs no interventions on HFS knowledge at up to 4 months follow up in school children and demonstrated significant difference between groups (very low quality, 2 RCTs, 535 participants, SMD 0.38, 95% CI: 0.21 to 0.55, p < 0.001). One study examined the effects of different modes of HFS interventions (computer-based vs instructor-led) on HFS knowledge and behaviour immediately post-intervention in adults and displayed no significant difference between groups (HFS knowledge; very low quality, 1 RCT, 68 participants, SMD -0.02, 95% CI: -0.50 to 0.45, p = 0.92) and (HFS behaviour; very low quality, 1 RCT, 68 participants, SMD 0.06, 95% CI: -0.41 to 0.54, p = 0.79) respectively.ConclusionThe limited evidence supports the use of HFS interventions to improve HFS knowledge and behaviour in children, families with children and adults.

A care cascade is a critical tool for evaluating delivery of care for chronic infections across sequential stages, starting with diagnosis and ending with viral suppression. However, there have been few data describing the hepatitis B virus (HBV) care cascade among people living with HIV infection who have HBV coinfection. We conducted a cross-sectional study among people living with HIV and HBV coinfection receiving care between January 1, 2012 and December 31, 2016 within 13 United States and Canadian clinical cohorts contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We evaluated each of the steps in this cascade, including: 1) laboratory-confirmed HBV infection, 2) tenofovir-based or entecavir-based HBV therapy prescribed, 3) HBV DNA measured during treatment, and 4) viral suppression achieved via undetectable HBV DNA. Among 3,953 persons with laboratory-confirmed HBV (median age, 50 years; 6.5% female; 43.8% were Black; 7.1% were Hispanic), 3,592 (90.9%; 95% confidence interval, 90.0-91.8%) were prescribed tenofovir-based antiretroviral therapy or entecavir along with their antiretroviral therapy regimen, 2,281 (57.7%; 95% confidence interval, 56.2-59.2%) had HBV DNA measured while on therapy, and 1,624 (41.1%; 95% confidence interval, 39.5-42.6) achieved an undetectable HBV DNA during HBV treatment. Our study identified significant gaps in measurement of HBV DNA and suppression of HBV viremia among people living with HIV and HBV coinfection in the United States and Canada. Periodic evaluation of the HBV care cascade among persons with HIV/HBV will be critical to monitoring success in completion of each step.

The All of Us (AoU) Research Program is making available one of the largest and most diverse collections of health data in the US to researchers. Using the All of Us database, we evaluated family and personal histories of five common types of cancer in 89,453 individuals, comparing these data to 24,305 participants from the 2015 National Health Interview Survey (NHIS). Comparing datasets, we found similar family cancer history (33%) rates, but higher personal cancer history in the AoU dataset (9.2% in AoU vs. 5.11% in NHIS), Methodological (e.g. survey-versus telephone-based data collection) and demographic variability may explain these between-data differences, but more research is needed.

BACKGROUND: Cardiac device infection (CDI) can occur in up to 2.2% of patients after device placement, with mortality rates exceeding 15%. Although device removal is standard management, the COVID-19 pandemic has been associated with resource diversion and decreased patient presentation for cardiovascular disease. We ascertained the association of the COVID-19 pandemic with outcomes and resource utilization after admission for CDI. METHODS: The 2016-2020 National Inpatient Sample was used to retrospectively study all adult admissions for CDI. Patients admitted between March and December, 2020 were classified as the pandemic cohort, with the rest pre-pandemic. The primary outcome was major adverse events (MAE), with secondary outcomes of overall length of stay (LOS), post-device removal LOS, time to device replacement, and hospitalization costs. MAE was a combination of in-hospital mortality and select complications. Multivariable regression models were developed to determine the relationship between the pandemic and the aforementioned outcomes. RESULTS: Of an estimated 190,160 patients, 14.3% comprised the pandemic cohort; 2.4% of these patients were COVID-19 positive. The pandemic cohort was older, less commonly female, and had higher rates of congestive heart failure. After adjustment, the pandemic was not associated with altered odds of MAE, device removal, or subsequent device replacement. The pandemic was, however, associated with decreased adjusted overall LOS (β -0.38 days) and days to device replacement (β -0.83 days). The pandemic was likewise associated with $2,000 increased adjusted hospitalization costs. CONCLUSION: The pandemic did not have a significant impact on clinical outcomes in patients admitted for CDI, despite higher hospitalization costs and decreased length of stay.

Tobacco smoking imposes a staggering burden on public health, underscoring the urgency of developing a deeper understanding of the processes that maintain addiction. Clinical and experience-sampling data highlight the importance of anxious withdrawal symptoms, but the underlying neurobiology has remained elusive. Mechanistic work in animals implicates the central extended amygdala (EAc)-including the central nucleus of the amygdala and the neighboring bed nucleus of the stria terminalis-but the translational relevance of these discoveries remains unexplored. Here we leveraged a randomized trial design, well-established threat-anticipation paradigm, and multidimensional battery of assessments to understand the consequences of 24-hour nicotine abstinence. The threat-anticipation paradigm had the expected consequences, amplifying subjective distress and arousal, and recruiting the canonical threat-anticipation network. Abstinence increased smoking urges and withdrawal symptoms, and potentiated threat-evoked distress, but had negligible consequences for EAc threat reactivity, raising questions about the translational relevance of prominent animal and human models of addiction. These observations provide a framework for conceptualizing nicotine abstinence and withdrawal, with implications for basic, translational, and clinical science.

Within the context of the novel coronavirus pandemic and new challenges to a resource-constrained public healthcare system, many healthcare workers in South Africa have faced numerous stressors that have compromised their mental health. While the current literature on COVID-19 in South Africa highlights the widespread psychosocial stress experienced by healthcare workers during the pandemic, little is known about the coping strategies utilized to continue service delivery and maintain ones mental health and well-being during this ongoing public health emergency. In this study, we sought to explore the coping strategies used by healthcare workers employed in the public psychiatric care system in southern Gauteng, South Africa during the coronavirus disease (COVID-19) pandemic. Psychiatric healthcare workers (n = 55) employed in three tertiary public hospitals and two specialized psychiatric facilities participated in in-depth interviews between July 2020 and March 2021. We found that coping strategies spanned multi-level and multi-systemic efforts. Intrapersonal, interpersonal, material, and structural coping were mapped across individual, family, and hospital systems. The most commonly utilized coping strategies included positive mindsets and reappraisal, social support systems, and COVID-19 specific protections. Findings also highlighted the contextual and interconnected nature of coping. Healthcare workers applied multiple coping strategies to combat the negative mental health effects of the COVID-19 pandemic. Better understanding these strategies, contexts in which they are employed, and how they interact can be used to develop evidence-based interventions to support healthcare workers experiencing healthcare-related stressors during the COVID-19 pandemic.

BackgroundWomen's childbirth experience of interpersonal care is a significant aspect of quality of care. Due to the lack of a reliable Cambodian version of a measurement tool to assess person-centered maternity care, the present study aimed to adapt the "Person-Centered Maternity Care (PCMC) scale" to the Cambodian context and further determine its psychometric properties.MethodsThe PCMC scale was translated into Khmer using the team translation approach. The Khmer version of PCMC (Kh-PCMC) scale was pretested among 20 Cambodian postpartum women using cognitive interviewing. Subsequently, the Kh-PCMC scale was administered in a survey with 300 Cambodian postpartum women at two governmental health facilities. According to the COnsensus-based Standards for the Selection of health status Measurement Instruments (COSMIN) standard, we performed psychometric analysis, including content validity, construct validity, criterion validity, cross-cultural validity, and internal consistency.ResultsThe preliminary processes of Kh-PCMC scale development including cognitive interviewing and expert review ensured appropriate levels of content validity and acceptable levels of cross-cultural validity of the Kh-PCMC scale with four-point frequency responses. The Scale-level Content Validity Index, Average (S-CVI/Avg) of 30-item Kh-PCMC scale was 0.96. Twenty items, however, performed optimally in the psychometric analysis from the data in Cambodia. The 20-item Kh-PCMC scale produced Cronbach's alpha of 0.86 for the full scale and 0.76-0.91 for the subscales, indicating adequately high internal consistency. Hypothesis testing found positive correlations between the 20-item Kh-PCMC scale and reference measures, which implies acceptable criterion validity.ConclusionsThe present study produced the Kh-PCMC scale that enables women's childbirth experiences to be quantitatively measured. The Kh-PCMC scale can identify intrapartum needs from women's perspectives for quality improvement in Cambodia. However, dynamic changes in and diverse differences of cultural context over time across provinces in Cambodia require the Kh-PCMC scale to be regularly reexamined and, when needed, to be further adjusted.

We investigate perceptions of tweets marked with the #BlackLivesMatter and #AllLivesMatter hashtags, as well as how the presence or absence of those hashtags changed the meaning and subsequent interpretation of tweets in U.S. participants. We found a strong effect of partisanship on perceptions of the tweets, such that participants on the political left were more likely to view #AllLivesMatter tweets as racist and offensive, while participants on the political right were more likely to view #BlackLivesMatter tweets as racist and offensive. Moreover, we found that political identity explained evaluation results far better than other measured demographics. Additionally, to assess the influence of hashtags themselves, we removed them from tweets in which they originally appeared and added them to selected neutral tweets. Our results have implications for our understanding of how social identity, and particularly political identity, shapes how individuals perceive and engage with the world.

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.MethodsRECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.DiscussionRECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.RegistrationNCT05172024.

BackgroundIn Cambodia, the importance of valuing women's childbirth experiences in improving quality of care has been understudied. This is largely because of absence of reliable Khmer tools for measuring women's intrapartum care experiences. Generally, cross-cultural development of those tools often involves translation from a source language into a target language. Yet, few earlier studies considered Cambodian cultural context. Thus, we developed the Cambodian version of the Person-Centered Maternity Care (PCMC) scale, by culturally adapting its original to Cambodian context for ensuring cultural equivalence and content validity.MethodsThree rounds of cognitive interviewing with 20 early postpartum women were conducted at two governmental health facilities in Cambodia. Cognitive interviewing was composed of structured questionnaire pretesting and qualitative probing. The issues identified in the process of transcribing and translating audio-recorded cognitive interviews were iteratively discussed among study team members, and further analyzed.ResultsA total of 14 issues related to cultural adaptations were identified in the 31 translated questions for the Cambodian version of the PCMC scale. Our study identified three key findings: (i) discrepancies between the WHO recommendations on intrapartum care and Cambodian field realities; (ii) discrepancies in recognition on PCMC between national experts and local women; and (iii) challenges in correctly collecting and interpreting less-educated women's views on intrapartum care.ConclusionNot only women's verbal data but also their non-verbal data and cultural contexts should be comprehensively counted, when reflecting Cambodian women's intrapartum practice realities in the translated version. This is the first study that attempted to develop the tool for measuring Cambodian women's experiences during childbirth, by addressing cross-cultural issues.

The use of publicly available sequencing datasets as controls (hereafter, "public controls") in studies of rare variant disease associations has great promise but can increase the risk of false-positive discovery. The specific factors that could contribute to inflated distribution of test statistics have not been systematically examined. Here, we leveraged both public controls, gnomAD v2.1 and several datasets sequenced in our laboratory to systematically investigate factors that could contribute to the false-positive discovery, as measured by λΔ95, a measure to quantify the degree of inflation in statistical significance. Analyses of datasets in this investigation found that 1) the significantly inflated distribution of test statistics decreased substantially when the same variant caller and filtering pipelines were employed, 2) differences in library prep kits and sequencers did not affect the false-positive discovery rate and, 3) joint vs. separate variant-calling of cases and controls did not contribute to the inflation of test statistics. Currently available methods do not adequately adjust for the high false-positive discovery. These results, especially if replicated, emphasize the risks of using public controls for rare-variant association tests in which individual-level data and the computational pipeline are not readily accessible, which prevents the use of the same variant-calling and filtering pipelines on both cases and controls. A plausible solution exists with the emergence of cloud-based computing, which can make it possible to bring containerized analytical pipelines to the data (rather than the data to the pipeline) and could avert or minimize these issues. It is suggested that future reports account for this issue and provide this as a limitation in reporting new findings based on studies that cannot practically analyze all data on a single pipeline.

People experience the same event but do not feel the same way. Such individual differences in emotion response are believed to be far greater than those in any other mental functions. Thus, to understand what makes people individuals, it is important to identify the systematic structures of individual differences in emotion response and elucidate how such structures relate to what aspects of psychological characteristics. Reflecting this importance, many studies have attempted to relate emotions to psychological characteristics such as personality traits, psychosocial states, and pathological symptoms across individuals. However, systematic and global structures that govern the across-individual covariation between the domain of emotion responses and that of psychological characteristics have been rarely explored previously, which limits our understanding of the relationship between individual differences in emotion response and psychological characteristics. To overcome this limitation, we acquired high-dimensional data sets in both emotion-response (8 measures) and psychological-characteristic (68 measures) domains from the same pool of individuals (86 undergraduate or graduate students) and carried out the canonical correlation analysis in conjunction with the principal component analysis on those data sets. For each participant, the emotion-response measures were quantified by regressing affective-rating responses to visual narrative stimuli onto the across-participant average responses to those stimuli, while the psychological-characteristic measures were acquired from 19 different psychometric questionnaires grounded in personality, psychosocial-factor, and clinical-problem taxonomies. We found a single robust mode of population covariation, particularly between the 'accuracy' and 'sensitivity' measures of arousal responses in the emotion domain and many 'psychosocial' measures in the psychological-characteristics domain. This mode of covariation suggests that individuals characterized with positive social assets tend to show polarized arousal responses to life events.

The ability of Mycobacterium tuberculosis (Mtb) to persist in its host may enable an evolutionary advantage for drug resistant variants to emerge. A potential strategy to prevent persistence and gain drug efficacy is to directly target the activity of enzymes that are crucial for persistence. We present a method for expedited discovery and structure-based design of lead compounds by targeting the hypoxia-associated enzyme L-alanine dehydrogenase (AlaDH). Biochemical and structural analyses of AlaDH confirmed binding of nucleoside derivatives and showed a site adjacent to the nucleoside binding pocket that can confer specificity to putative inhibitors. Using a combination of dye-ligand affinity chromatography, enzyme kinetics and protein crystallographic studies, we show the development and validation of drug prototypes. Crystal structures of AlaDH-inhibitor complexes with variations at the N6 position of the adenyl-moiety of the inhibitor provide insight into the molecular basis for the specificity of these compounds. We describe a drug-designing pipeline that aims to block Mtb to proliferate upon re-oxygenation by specifically blocking NAD accessibility to AlaDH. The collective approach to drug discovery was further evaluated through in silico analyses providing additional insight into an efficient drug development strategy that can be further assessed with the incorporation of in vivo studies.

Soil disinfestation with steam was evaluated as an alternative to fumigation. Following soil disinfestation, plant health has traditionally been measured using plant size and yield. Plant health can be measured in a timely manner more efficiently, more easily and non-destructively using image analysis. We hypothesized that plant health could be quantified and treatments can be differentiated using an RGB (Red, Green, Blue) image analysis program, particularly by observing the greenness of plant leaves. However, plant size or the proportion of green area could be unreliable due to plant loss and camera's position and angle. To this end, we decided to evaluate plant health by analyzing the RGB codes associated with the green color only, which detects the chlorophyll reflectance and nutrient status, noting that the degree of greenness within the green-leaf-area was not affected by the plant size. We identified five RGB codes that are commonly observed in the plant leaves and ordered them from dark green to light green. Among the five RGB codes, the relative percentage covered by the darkest green to the lightest green was significantly different between the steam and chloropicrin treatments and the control, and it was not significantly different between the steam and chloropicrin treatments. Furthermore, the result was correlated with the total yield, and the trend observed in the first year was replicated in the second year of this experiment. In this study, we demonstrate that the RGB image analysis can be used as an early marker of the treatment effect on the plant health and productivity.

Despite significant improvements in life expectancy of kidney transplant patients due to advances in surgery and immunosuppression, Chronic Allograft Nephropathy (CAN) remains a daunting problem. A complex network of cellular mechanisms in both graft and peripheral immune compartments complicates the non-invasive diagnosis of CAN, which still requires biopsy histology. This is compounded by non-immunological factors contributing to graft injury. There is a pressing need to identify and validate minimally invasive biomarkers for CAN to serve as early predictors of graft loss and as metrics for managing long-term immunosuppression.We used DNA microarrays, tandem mass spectroscopy proteomics and bioinformatics to identify genomic and proteomic markers of mild and moderate/severe CAN in peripheral blood of two distinct cohorts (n = 77 total) of kidney transplant patients with biopsy-documented histology.Gene expression profiles reveal over 2400 genes for mild CAN, and over 700 for moderate/severe CAN. A consensus analysis reveals 393 (mild) and 63 (moderate/severe) final candidates as CAN markers with predictive accuracy of 80% (mild) and 92% (moderate/severe). Proteomic profiles show over 500 candidates each, for both stages of CAN including 302 proteins unique to mild and 509 unique to moderate/severe CAN.This study identifies several unique signatures of transcript and protein biomarkers with high predictive accuracies for mild and moderate/severe CAN, the most common cause of late allograft failure. These biomarkers are the necessary first step to a proteogenomic classification of CAN based on peripheral blood profiling and will be the targets of a prospective clinical validation study.

Social-emotional learning (SEL) is an educational model for improving social-emotional competences of all students and a long-term education program connecting school, home, and community. Although there has been active research to establish evidence-based practice (EBP) of SEL programs worldwide, the quality of SEL intervention studies which is an integral part of evaluating EBP was rarely investigated. In addition, prior meta-analytic studies focused only on the effectiveness of SEL programs conducted in Western society. In this sense, in order to contribute to establishing EBP of SEL programs, the current research sought to analyze both quality and effectiveness of SEL intervention studies conducted in Korea where SEL has been investigated and applied in classroom since 2010. To conduct this study, we selected 22 peer-reviewed articles (about 23 SEL programs) and analyzed their quality by Evidence-Based Intervention (EBI) indicators and calculated effect sizes using a meta-analysis. The results of the quality analysis revealed that SEL intervention studies had some limitations with a statistical analysis, use of measurement, a control group design, intervention fidelity, and external validity. The global effect size of SEL programs was 0.27, and the results from the effect size analyses by controlling variables showed that group compositions, the number of sessions, and session length were accountable for the variability of effect sizes. Based on these findings, we discussed the directions for future research and practice on the EBP of SEL programs that can be appreciated by researchers worldwide.

BACKGROUND: Respiratory syncytial virus (RSV) can cause severe disease in adults with cardiopulmonary conditions, such as congestive heart failure (CHF). We quantified the rate of RSV-associated hospitalization in adults by CHF status using population-based surveillance in the United States. METHODS: Population-based surveillance for RSV (RSV-NET) was performed in 35 counties in seven sites during two respiratory seasons (2015-2017) from October 1-April 30. Adults (≥18 years) admitted to a hospital within the surveillance catchment area with laboratory-confirmed RSV identified by clinician-directed testing were included. Presence of underlying CHF was determined by medical chart abstraction. We calculated overall and age-stratified (

Differences in national responses to COVID-19 have been associated with the cultural value of collectivism. The present research builds on these findings by examining the relationship between collectivism at the individual level and adherence to public health recommendations to combat COVID-19 during the pre-vaccination stage of the pandemic, and examines different characteristics of collectivism (i.e., concern for community, trust in institutions, perceived social norms) as potential psychological mechanisms that could explain greater compliance. A study with a cross-section of American participants (N = 530) examined the relationship between collectivism and opting-in to digital contact tracing (DCT) and wearing face coverings in the general population. More collectivistic individuals were more likely to comply with public health interventions than less collectivistic individuals. While collectivism was positively associated with the three potential psychological mechanisms, only perceived social norms about the proportion of people performing the public health interventions explained the relationship between collectivism and compliance with both public health interventions. This research identifies specific pathways by which collectivism can lead to compliance with community-benefiting public health behaviors to combat contagious diseases and highlights the role of cultural orientation in shaping individuals decisions that involve a tension between individual cost and community benefit.

A linking procedure establishes a "bridge" between the scores from different patient-reported outcome (PRO) instruments that measure similar constructs. After developing a linking relationship however, it is critical to evaluate whether this relationship can be generalized to different groups. Our study aims to validate a published crosswalk for score conversion between the Brief Symptom Inventory Depression subscale and the Patient-Reported Outcomes Measurement Information System Depression 8a using an independent sample. Data were from a sample of young men who have sex with men (MSM), which differs in terms of participant age, race, and ethnicity from the sample used to develop the existing crosswalk. The validity of the newly derived crosswalk was evaluated in terms of the correlation, mean difference and standard deviation between the observed and the linked scores. The two crosswalks were further compared to evaluate if the difference was within an acceptable range. More than half of the item parameters obtained from the two samples were found to overlap in their confidence intervals. Differences between each pair of scores in the two crosswalks was within three T-score points, well within the range of each crosswalk score's standard error. This study concludes that an existing crosswalk is replicable on a sample that differs from that used for crosswalk development, but future research should continue to examine the generalizability of the linked parameters and evaluate the reproducibility of this crosswalk to other populations.

BackgroundPersistent inflammation following vascular injury drives neointimal hyperplasia (NIH). Specialized lipid mediators (SPM) mediate resolution which attenuates inflammation and downstream NIH. We investigated the effects of a synthetic analogue of resolvin D1 (RvD1) on vascular cells and in a model of rat carotid angioplasty.MethodsHuman venous VSMC and endothelial cells (EC) were employed in migration, cell shape, toxicity, proliferation and p65 nuclear translocation assays. Murine RAW 264.7 cells were utilized to test the effect of pro-resolving compounds on phagocytic activity. A model of rat carotid angioplasty was used to evaluate the effects of 17R/S-benzo-RvD1 (benzo-RvD1) and 17R-RvD1 applied to the adventitia via 25% Pluronic gel. Immunostaining was utilized to examine Ki67 expression and leukocyte recruitment. Morphometric analysis was performed on arteries harvested 14 days after injury.ResultsExposure to benzo-RvD1 attenuated PDGF- stimulated VSMC migration across a range of concentrations (0.1-100 nM), similar to that observed with 17R-RvD1. Pre-treatment with either Benzo-RvD1 or 17R-RvD1 (10, 100nM) attenuated PDGF-BB-induced VSMC cytoskeletal changes to nearly baseline dimensions. Benzo-RvD1 demonstrated modest anti-proliferative activity on VSMC and EC at various concentrations, without significant cytotoxicity. Benzo-RvD1 (10nM) inhibited p65 nuclear translocation in cytokine-stimulated EC by 21% (p

Main objectiveThere is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic.Study design and methodsUniversity of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission.Results and significanceThe 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months.ConclusionsMortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes.Trial registrationClinicalTrials.gov Identifier: NCT04506528 (https://clinicaltrials.gov/ct2/show/NCT04506528).

IntroductionThe NIH All of Us Research Program will have the scale and scope to enable research for a wide range of diseases, including cancer. The program's focus on diversity and inclusion promises a better understanding of the unequal burden of cancer. Preliminary cancer ascertainment in the All of Us cohort from two data sources (self-reported versus electronic health records (EHR)) is considered.Materials and methodsThis work was performed on data collected from the All of Us Research Program's 315,297 enrolled participants to date using the Researcher Workbench, where approved researchers can access and analyze All of Us data on cancer and other diseases. Cancer case ascertainment was performed using data from EHR and self-reported surveys across key factors. Distribution of cancer types and concordance of data sources by cancer site and demographics is analyzed.Results and discussionData collected from 315,297 participants resulted in 13,298 cancer cases detected in the survey (in 89,261 participants), 23,520 cancer cases detected in the EHR (in 203,813 participants), and 7,123 cancer cases detected across both sources (in 62,497 participants). Key differences in survey completion by race/ethnicity impacted the makeup of cohorts when compared to cancer in the EHR and national NCI SEER data.ConclusionsThis study provides key insight into cancer detection in the All of Us Research Program and points to the existing strengths and limitations of All of Us as a platform for cancer research now and in the future.

Childhood undernutrition is a major health burden worldwide that increases childhood morbidity and mortality and causes impairment in infant growth and developmental delays that can persist into adulthood. The first weeks and months after birth are critical to the establishment of healthy growth and development during childhood. The World Health Organization recommends immediate and exclusive breastfeeding (EBF). In infants for whom EBF may not meet nutritional and caloric demands, early, daily, small-volume formula supplementation along with breastfeeding may more effectively avoid underweight wasting and stunting in early infancy than breastfeeding alone. The primary objective of this randomized controlled trial is to evaluate the efficacy of formula for 30 days among low birth weight (LBW) infants

BackgroundExposure to trauma can result in various mental health disorders including anxiety, depression, and posttraumatic stress disorder (PTSD). Although psychotherapies and pharmacotherapies exist for the treatment of these disorders, many individuals fail to receive treatment and among those who do, many remain symptomatic. Therefore, it is critical to continue developing new interventions for traumatic stress that target underlying mechanisms of pathology and offer a safe and acceptable alternative to current treatments. Morning light treatment has good potential as a novel non-invasive, low risk treatment for traumatic stress. Evidence suggests that morning light may improve traumatic stress by reducing reactivity in the amygdala, a brain region implicated in the pathophysiology of PTSD and anatomically linked to circadian photoreceptors in the eye.MethodsIn this study, we aim to establish a significant dose-response relationship between duration of morning light treatment and reduction in amygdala reactivity among individuals with traumatic stress symptoms (NCT# 04117347). Using a transdiagnostic approach, sixty-six individuals with a history of a DSM-5 criterion A trauma and traumatic stress symptoms will be recruited to participate in a 5-week study. Participants will be randomized across three treatment arms based on morning light treatment duration: 15-minutes, 30-minutes, or 60-minutes of light treatment per day for four weeks. To evaluate amygdala activity, participants will undergo fMRI at pre-treatment, mid-treatment, and post-treatment. Participants will also complete clinical assessments and self-report measures of PTSD, depression, and anxiety at pre-treatment, mid-treatment, and post-treatment.DiscussionMorning light therapy may be an acceptable, feasible, and effective treatment for individuals suffering from traumatic stress. Identifying mechanistically relevant targets, and the doses needed to impact them, are critical steps in developing this new treatment approach for the sequelae of traumatic stress.

Power laws are of interest to several scientific disciplines because they can provide important information about the underlying dynamics (e.g. scale invariance and self-similarity) of a given system. Because power laws are of increasing interest to the cardiac sciences as potential indicators of cardiac dysfunction, it is essential that rigorous, standardized analytical methods are employed in the evaluation of power laws. This study compares the methods currently used in the fields of condensed matter physics, geoscience, neuroscience, and cardiology in order to provide a robust analytical framework for evaluating power laws in stem cell-derived cardiomyocyte cultures. One potential power law-obeying phenomenon observed in these cultures is pacemaker translocations, or the spatial and temporal instability of the pacemaker region, in a 2D cell culture. Power law analysis of translocation data was performed using increasingly rigorous methods in order to illustrate how differences in analytical robustness can result in misleading power law interpretations. Non-robust methods concluded that pacemaker translocations adhere to a power law while robust methods convincingly demonstrated that they obey a doubly truncated power law. The results of this study highlight the importance of employing comprehensive methods during power law analysis of cardiomyocyte cultures.

Open source analytical software for the analysis of electrophysiological cardiomyocyte data offers a variety of new functionalities to complement closed-source, proprietary tools. Here, we present the Cardio PyMEA application, a free, modifiable, and open source program for the analysis of microelectrode array (MEA) data obtained from cardiomyocyte cultures. Major software capabilities include: beat detection; pacemaker origin estimation; beat amplitude and interval; local activation time, upstroke velocity, and conduction velocity; analysis of cardiomyocyte property-distance relationships; and robust power law analysis of pacemaker spatiotemporal instability. Cardio PyMEA was written entirely in Python 3 to provide an accessible, integrated workflow that possesses a user-friendly graphical user interface (GUI) written in PyQt5 to allow for performant, cross-platform utilization. This application makes use of object-oriented programming (OOP) principles to facilitate the relatively straightforward incorporation of custom functionalities, e.g. power law analysis, that suit the needs of the user. Cardio PyMEA is available as an open source application under the terms of the GNU General Public License (GPL). The source code for Cardio PyMEA can be downloaded from Github at the following repository: https://github.com/csdunhamUC/cardio_pymea.

Testing surfaces in school classrooms for the presence of SARS-CoV-2, the virus that causes COVID-19, can provide public-health information that complements clinical testing. We monitored the presence of SARS-CoV-2 RNA in five schools (96 classrooms) in Davis, California (USA) by collecting weekly surface-swab samples from classroom floors and/or portable high-efficiency particulate air (HEPA) units (n = 2,341 swabs). Twenty-two surfaces tested positive, with qPCR cycle threshold (Ct) values ranging from 36.07-38.01. Intermittent repeated positives in a single room were observed for both floor and HEPA filter samples for up to 52 days, even following regular cleaning and HEPA filter replacement after a positive result. We compared the two environmental sampling strategies by testing one floor and two HEPA filter samples in 57 classrooms at Schools D and E. HEPA filter sampling yielded 3.02% and 0.41% positivity rates per filter sample collected for Schools D and E, respectively, while floor sampling yielded 0.48% and 0% positivity rates. Our results indicate that HEPA filter swabs are more sensitive than floor swabs at detecting SARS-CoV-2 RNA in interior spaces. During the study, all schools were offered weekly free COVID-19 clinical testing through Healthy Davis Together (HDT). HDT also offered on-site clinical testing in Schools D and E, and upticks in testing participation were observed following a confirmed positive environmental sample. However, no confirmed COVID-19 cases were identified among students associated with classrooms yielding positive environmental samples. The positive samples detected in this study appeared to contain relic viral RNA from individuals infected before the monitoring program started and/or RNA transported into classrooms via fomites. High-Ct positive results from environmental swabs detected in the absence of known active infections supports this conclusion. Additional research is needed to differentiate between fresh and relic SARS-CoV-2 RNA in environmental samples and to determine what types of results should trigger interventions.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

ObjectivesSome studies suggested more COVID-19-associated hospitalizations among racial and ethnic minorities. To inform public health practice, the COVID-19-associated Hospitalization Surveillance Network (COVID-NET) quantified associations between race/ethnicity, census tract socioeconomic indicators, and COVID-19-associated hospitalization rates.MethodsUsing data from COVID-NET population-based surveillance reported during March 1-April 30, 2020 along with socioeconomic and denominator data from the US Census Bureau, we calculated COVID-19-associated hospitalization rates by racial/ethnic and census tract-level socioeconomic strata.ResultsAmong 16,000 COVID-19-associated hospitalizations, 34.8% occurred among non-Hispanic White (White) persons, 36.3% among non-Hispanic Black (Black) persons, and 18.2% among Hispanic or Latino (Hispanic) persons. Age-adjusted COVID-19-associated hospitalization rate were 151.6 (95% Confidence Interval (CI): 147.1-156.1) in census tracts with >15.2%-83.2% of persons living below the federal poverty level (high-poverty census tracts) and 75.5 (95% CI: 72.9-78.1) in census tracts with 0%-4.9% of persons living below the federal poverty level (low-poverty census tracts). Among White, Black, and Hispanic persons living in high-poverty census tracts, age-adjusted hospitalization rates were 120.3 (95% CI: 112.3-128.2), 252.2 (95% CI: 241.4-263.0), and 341.1 (95% CI: 317.3-365.0), respectively, compared with 58.2 (95% CI: 55.4-61.1), 304.0 (95%: 282.4-325.6), and 540.3 (95% CI: 477.0-603.6), respectively, in low-poverty census tracts.ConclusionsOverall, COVID-19-associated hospitalization rates were highest in high-poverty census tracts, but rates among Black and Hispanic persons were high regardless of poverty level. Public health practitioners must ensure mitigation measures and vaccination campaigns address needs of racial/ethnic minority groups and people living in high-poverty census tracts.

ObjectiveThis population-based, matched cohort study aimed to evaluate utilization of health care services by mothers of children with major congenital anomalies (MCAs), compared to mothers of children without MCAs over a 20-year post-birth time horizon in Denmark.MethodsOur analytic sample included mothers who gave birth to an infant with a MCA (n = 23,927) and a cohort of mothers matched to them by maternal age, parity and infant's year of birth (n = 239,076). Primary outcomes were period prevalence and mothers' quantity of health care utilization (primary, inpatient, outpatient, surgical, and psychiatric services) stratified by their child's age (i.e., ages 0-6 = before school, ages 7-13 = pre-school + primary education, and ages 14-18 = secondary education or higher). The secondary outcome measure was length of hospital stays. Outcome measures were adjusted for maternal age at delivery, parity, marital status, income quartile, level of education in the year prior to the index birth, previous spontaneous abortions, maternal pregnancy complications, maternal diabetes, hypertension, alcohol-related diseases, and maternal smoking.ResultsIn both cohorts the majority of mothers were between 26 and 35 years of age, married, and employed, and 47% were primiparous. Mothers of infants with anomalies had greater utilization of outpatient, inpatient, surgical, and psychiatric services, compared with mothers in the matched cohort. Inpatient service utilization was greater in the exposed cohort up to 13 years after a child's birth, with the highest risk in the first six years after birth [adjusted risk ratio, 1.13; 95% confidence interval (CI), 1.12-1.14], with a decrease over time. Regarding the quantity of health care utilization, the greatest difference between the two groups was in inpatient service utilization, with a 39% increased rate in the exposed cohort during the first six years after birth (adjusted rate ratio, 1.39; 95% CI, 1.37-1.42). During the first 6 years after birth, mothers of children with anomalies stayed a median of 6 days (interquartile range [IQR], 3-13) in hospital overall, while the comparison cohort stayed a median of 4 days (IQR, 2-7) in hospital overall. Rates of utilization of outpatient clinics (adjusted rate ratio, 1.36; 95% CI, 1.29-1.42), as well as inpatient (adjusted rate ratio, 1.77; 95% CI, 1.68-1.87), and surgical services (adjusted rate ratio, 1.33; 95% CI, 1.26-1.41) was higher in mothers of children with multiple-organ MCAs during 0 to 6 years after birth. Among mothers at the lowest income levels, utilization of psychiatric clinic services increased to 59% and when their child was 7 to 13 years of age (adjusted rate ratio, 1.59; 95% CI, 1.24-2.03).ConclusionMothers of infants with a major congenital anomaly had greater health care utilization across services. Health care utilization decreased over time or remained stable for outpatient, inpatient, and surgical care services, whereas psychiatric utilization increased for up to 13 years after an affected child's birth. Healthcare utilization was significantly elevated among mothers of children with multiple MCAs and among those at the lowest income levels.

ObjectiveTo evaluate the combination of pembrolizumab, cisplatin and gemcitabine in recurrent platinum-resistant ovarian cancer.MethodsPatients received six cycles of chemotherapy with gemcitabine and cisplatin on day 1 and day 8 of a 21-day treatment cycle. Pembrolizumab was administered on day 1 of cycles 3-6 and as maintenance monotherapy in cycles 7-34. Palliative radiation to a non-target symptomatic lesion was allowed. The primary objective was overall response rate by RECIST 1.1 criteria. Secondary objectives included safety, progression-free survival, time to progression, duration of response and overall survival.ResultsAn interim analysis for futility was performed at 18 evaluable patients. Overall response rate was 60%, duration of response was 4.9 months and time to progression was 5.2 months. Progression-free survival at 6 and 12 months was 43% and 5%. Median progression-free survival was 6.2 months and median overall survival was 11.3 months. In all patients, CA125 levels reflected response and progression. There were no pseudoprogression events. After receiving palliative radiation during pembrolizumab maintenance, a patient with recurrent ovarian clear cell carcinoma had an exceptional and durable response that is ongoing for greater than 2 years. After consultation with the sponsor, based on the modest duration of response observed at the interim analysis for futility, the decision was made to close the trial to further accrual.ConclusionsThe addition of pembrolizumab to cisplatin and gemcitabine did not appear to provide benefit beyond chemotherapy alone in patients with recurrent platinum-resistant ovarian cancer.

Viral infection and pathogenesis is mediated by host protein-viral protein complexes that are important targets for therapeutic intervention as they are potentially less prone to development of drug resistance. We have identified human, recombinant antibodies (Fabs) from a phage display library that bind to three HIV-host complexes. We used these Fabs to 1) stabilize the complexes for structural studies; and 2) facilitate characterization of the function of these complexes. Specifically, we generated recombinant Fabs to Vif-CBF-β-ELOB-ELOC (VCBC); ESCRT-I complex and AP2-complex. For each complex we measured binding affinities with KD values of Fabs ranging from 12-419 nM and performed negative stain electron microscopy (nsEM) to obtain low-resolution structures of the HIV-Fab complexes. Select Fabs were converted to scFvs to allow them to fold intracellularly and perturb HIV-host protein complex assembly without affecting other pathways. To identify these recombinant Fabs, we developed a rapid screening pipeline that uses quantitative ELISAs and nsEM to establish whether the Fabs have overlapping or independent epitopes. This pipeline approach is generally applicable to other particularly challenging antigens that are refractory to immunization strategies for antibody generation including multi-protein complexes providing specific, reproducible, and renewable antibody reagents for research and clinical applications. The curated antibodies described here are available to the scientific community for further structural and functional studies on these critical HIV host-factor proteins.

Objective: To assess the knowledge levels and fertility preservation (FP) intentions of urban Chinese cancer patients. Methods: A cross-sectional study was conducted on Hong Kong Chinese male and female cancer patients aged 18–54 years (N = 325) who were recruited by a local non-governmental organization for cancer patients between July 2020 to January 2021. Patients completed a self-administered questionnaire on knowledge, perceptions, and intentions to use FP services/seek FP-related information. Multivariable logistic regression was used to explore the correlates of intention to seek additional FP information and intention to undergo FP treatments. Results: Although cancer patients demonstrated a good knowledge of the available FP treatment options, they were less knowledgeable about the legal restrictions of these procedures. Only one in seven cancer patients first became aware of FP through a health provider and the majority of cancer patients felt they did not have adequate knowledge about FP to make informed FP decisions at the current time. Yet, over one-third of cancer patients would consider FP options even if their cancer or cancer treatment had < 5% chance of causing infertility, and 13.4% of females and 14.6% of males would delay their cancer treatment by ≥ 3 months to undergo FP procedures. However, for both sexes, the main perceived barrier to obtaining FP was its financial cost. Patients with older-aged spouses were less likely to seek FP treatments or seek more information about FP. Conclusion: There is an unmet need for more FP information and FP services for reproductive-aged cancer patients in East Asian populations. Greater integration of FP services into cancer treatment requires a reduction of cost barriers, greater provision of timely FP information, and improved referral systems. [ABSTRACT FROM AUTHOR]

We aimed to develop efficient data labeling strategies for ground truth segmentation in lower-leg magnetic resonance imaging (MRI) of patients with Charcot-Marie-Tooth disease (CMT) and to develop an automated muscle segmentation model using different labeling approaches. The impact of using unlabeled data on model performance was further examined. Using axial T1-weighted MRIs of 120 patients with CMT (60 each with mild and severe intramuscular fat infiltration), we compared the performance of segmentation models obtained using several different labeling strategies. The effect of leveraging unlabeled data on segmentation performance was evaluated by comparing the performances of few-supervised, semi-supervised (mean teacher model), and fully-supervised learning models. We employed a 2D U-Net architecture and assessed its performance by comparing the average Dice coefficients (ADC) using paired t-tests with Bonferroni correction. Among few-supervised models utilizing 10% labeled data, labeling three slices (the uppermost, central, and lowermost slices) per subject exhibited a significantly higher ADC (90.84±3.46%) compared with other strategies using a single image slice per subject (uppermost, 87.79±4.41%; central, 89.42±4.07%; lowermost, 89.29±4.71%, p < 0.0001) or all slices per subject (85.97±9.82%, p < 0.0001). Moreover, semi-supervised learning significantly enhanced the segmentation performance. The semi-supervised model using the three-slices strategy showed the highest segmentation performance (91.03±3.67%) among 10% labeled set models. Fully-supervised model showed an ADC of 91.39±3.76. A three-slice-based labeling strategy for ground truth segmentation is the most efficient method for developing automated muscle segmentation models of CMT lower leg MRI. Additionally, semi-supervised learning with unlabeled data significantly enhances segmentation performance. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) results from sudden accidents, leading to brain damage, subsequent organ dysfunction, and potentially death. Despite extensive studies on rodent TBI models, there is still high variability in terms of target points, and this results in significantly different symptoms between models. In this study, we established a more concise and effective TBI mouse model, which included locomotor dysfunctions with increased apoptosis, based on the controlled cortical impact method. Behavioral tests, such as elevated body swing, rotarod, and cylinder tests were performed to assess the validity of our model. To investigate the underlying mechanisms of injury, we analyzed the expression of proteins associated with immune response and the apoptosis signaling pathway via western blotting analysis and immunohistochemistry. Upon TBI induction, the mouse subjects showed motor dysfunctions and asymmetric behavioral assessment. The expression of Bax gradually increased over time and reached its maximum 3 days post-surgery, and then declined. The expression of Mcl-1 showed a similar trend to Bax. Furthermore, the expression of caspase-3, ROCK1, and p53 were highly elevated by 3 days post-surgery and then declined by 7 days post-surgery. Importantly, immunohistochemistry revealed an immediate increase in the level of Bcl-2 at the lesion site upon TBI induction. Also, we found that the expression of neuronal markers, such as NeuN and MAP2, decreased after the surgery. Interestingly, the increase in NFH level was in line with the symptoms of TBI in humans. Collectively, our study demonstrated that the established TBI model induces motor dysfunction, hemorrhaging, infarctions, and apoptosis, closely resembling TBI in humans. Therefore, we predict that our model may be useful for developing effective treatment option for TBI. [ABSTRACT FROM AUTHOR]

Purpose: To represent 24–2 visual field (VF) losses of individual patients using a hybrid approach of archetypal analysis (AA) and fuzzy c-means (FCM) clustering. Methods: In this multicenter retrospective study, we classified characteristic patterns of 24–2 VF using AA and decomposed them with FCM clustering. We predicted the change in mean deviation (MD) through supervised machine learning from decomposition coefficient change. In addition, we compared the areas under the receiver operating characteristic curves (AUCs) of the decomposition coefficient slopes to detect VF progression using three criteria: MD slope, Visual Field Index slope, and pointwise linear regression analysis. Results: We identified 16 characteristic patterns (archetypes or ATs) of 24–2 VF from 132,938 VFs of 18,033 participants using AA. The hybrid approach using FCM revealed a lower mean squared error and greater correlation coefficient than the AA single approach for predicting MD change (all P ≤ 0.001). Three of 16 AUCs of the FCM decomposition coefficient slopes outperformed the AA decomposition coefficient slopes in detecting VF progression for all three criteria (AT5, superior altitudinal defect; AT10, double arcuate defect; AT13, total loss) (all P ≤ 0.028). Conclusion: A hybrid approach combining AA and FCM to analyze 24–2 VF can visualize VF tests in characteristic patterns and enhance detection of VF progression with lossless decomposition. [ABSTRACT FROM AUTHOR]

Bicuspid aortic valve (BAV), the most common congenital heart defect, is a major cause of aortic valve disease requiring valve interventions and thoracic aortic aneurysms predisposing to acute aortic dissections. The spectrum of BAV ranges from early onset valve and aortic complications (EBAV) to sporadic late onset disease. Rare genomic copy number variants (CNVs) have previously been implicated in the development of BAV and thoracic aortic aneurysms. We determined the frequency and gene content of rare CNVs in EBAV probands (n = 272) using genome-wide SNP microarray analysis and three complementary CNV detection algorithms (cnvPartition, PennCNV, and QuantiSNP). Unselected control genotypes from the Database of Genotypes and Phenotypes were analyzed using identical methods. We filtered the data to select large genic CNVs that were detected by multiple algorithms. Findings were replicated in a BAV cohort with late onset sporadic disease (n = 5040). We identified 3 large and rare (< 1,1000 in controls) CNVs in EBAV probands. The burden of CNVs intersecting with genes known to cause BAV when mutated was increased in case-control analysis. CNVs intersecting with GATA4 and DSCAM were enriched in cases, recurrent in other datasets, and segregated with disease in families. In total, we identified potentially pathogenic CNVs in 9% of EBAV cases, implicating alterations of candidate genes at these loci in the pathogenesis of BAV. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the risk of visual impairment (VI) based on the presence or absence of four diseases: hypertension (HTN), diabetes mellitus (DM), glaucoma, and diabetic retinopathy (DR). Methods: This retrospective population-based study included 1,000,000 randomly selected participants from the National Health Checkup Program database between 2015 and 2016. VI was defined as a presenting visual acuity ≤ 0.5 in the better eye. The participants were divided into 12 groups according to the presence or absence of disease. Adjusting for age and sex, the risk of VI in each disease group was analyzed and compared with the others. Results: Among the 1,000,000 participants, 88,931 (8.89%) had VI. The odds ratios (ORs) of age, male sex, HTN, DM, glaucoma, and DR for VI were 1.06 (95% CI, 1.05–1.06), 0.52 (95% CI, 0.52–0.53), 1.11 (95% CI, 1.09–1.13), 1.07 (95% CI, 1.05–1.09), 0.92 (95% CI, 0.90–0.74), and 1.29 (95% CI, 1.25–1.34), respectively (all P < 0.001). The group with HTN, DM, glaucoma, and DR had the highest OR of 1.98 (P < 0.001) compared to the healthy group. HTN, DM, and DR were positively correlated with VI in all groups. Glaucoma was positively correlated in the group with DM and DR and in the group with HTN, DM, and DR (ORs 1.18, 1.11, all P < 0.05); however, it demonstrated a negative correlation in the other groups (ORs 0.85–0.93, all P < 0.05). Conclusion: HTN, DM, and DR, either alone or in combination, increase the risk of VI. Glaucoma also increases the risk when combined with DR; however, it has a negative correlation with VI in the absence of DR. Periodic ophthalmologic examinations for glaucoma, which primarily affects the peripheral visual field and not central visual acuity, might help prevent VI caused by other diseases. [ABSTRACT FROM AUTHOR]

Background: Clustering lifestyle risk behaviors is important for predicting cardiovascular disease risk. However, it is unclear which behavior mediates other ones to influence cardiovascular disease risk. We aimed to assess the causal inference of each lifestyle risk behavior for the atherosclerotic cardiovascular disease (ASCVD) risk of the general population. Methods: We performed a Bayesian network mediation analysis using data from the Korea National Health and Nutrition Examination Survey from 2014 to 2019. The main exposure was a combination of lifestyle risk behaviors including unhealthy weight, heavy alcohol consumption, inadequate sleep, physical inactivity, excessive sodium intake, and current smoking among subjects 40 to 79 years of age. The high risk of ASCVD (≥7.5% for the 10-year risk) was assessed using logistic regression, Bayesian networks, and structural equational models to examine the causal relationships between these six lifestyle risk behaviors. Results: Among all participants, the most prevalent lifestyle risk behavior for those at high risk for ASCVD was excessive sodium intake (95.6%), followed by inadequate sleep (49.9%) and physical inactivity (43.8%). Older age (65–79 years) and male sex were directly associated with a high risk for ASCVD. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight indirectly mediated the effects of older age (8.2% of the older age) and male sex (39.9% of males) to high ASCVD risk. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight particularly mediated the high ASCVD risk sequentially. Heavy alcohol consumption and inadequate sleep were not directly associated with high ASCVD risk and did not indirectly mediate the effects of older age and males on the high ASCVD risk. Conclusion: Lifestyle risk behaviors mediated the atherosclerotic cardiovascular disease risk in a different manner. Especially, physical inactivity preceded current smoking, excessive sodium intake, and unhealthy weight in relation to high ASCVD risk, and this causal relationship was different according to age and sex. Therefore, tailored strategies according to specific target populations may be needed to effectively reduce the high ASCVD risk. [ABSTRACT FROM AUTHOR]

Although gastroesophageal reflux has been recognized as one of the risk factors of nontuberculous mycobacterial pulmonary disease (NTM-PD) progression, the effect of reflux on the lower respiratory tract microbiota has not been studied in detail. We investigated the composition of the lower respiratory tract microbiota in patients with clinically suspected NTM-PD, comparing them based on the presence of reflux. Forty-seven patients suspected of having NTM-PD were enrolled and assigned according to presence of reflux (n = 22) and non- reflux (n = 25). We performed a pepsin ELISA assay to identify the presence of reflux and 16S ribosomal RNA gene amplicon sequencing to evaluate the microbiota in bronchoalveolar lavage fluid. There were no significant differences in the diversity or composition of the lower respiratory microbiota between the NTM-PD and non-NTM-PD groups. Bacterial richness was observed in the non-reflux group than in the reflux group [P = 0.03] and a cluster in the reflux group was observed. The reflux group showed a predominance for Pseudomonas aeruginosa or Staphylococcus aureus among the NTM-PD group and for P. aeruginosa, Haemophilus influenzae, Klebsiella pneumoniae, or Eikenella species among the non-NTM-PD group. The non-reflux groups presented diverse patterns. A linear discriminant analysis and volcano plot demonstrated that P. aeruginosa, H. haemolyticus, Selenomonas artemidis, and Dolosigranulum pigrum were specifically associated with the NTM-PD reflux group, while P. aeruginosa was specifically associated with the non-NTM-PD reflux group. These observations confirm that the lower respiratory microbiota is consistently altered by reflux but not in NTM-PD. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to predict future visual field tests using a bidirectional gated recurrent unit (Bi-GRU) and assess its performance based on the number of input visual field tests and the prediction time interval. Materials and methods: This study included patients who underwent visual field tests at least four times at five university hospitals between June 2004 and April 2022. All data were accessed in October 2022 for research purposes. In total, 23,517 eyes with 185,858 visual field tests were used as the training dataset, and 1,053 eyes with 9,459 visual field tests were used as the test dataset. The Bi-GRU architecture was designed to take a variable number of visual field tests, ranging from 3 to 80, as input and predict visual field tests at the desired arbitrary time point. It generated the mean deviation (MD), pattern standard deviation (PSD), Visual Field Index (VFI), and total deviation value (TDV) for 54 test points. To analyze the model performance, the mean absolute error between the actual and predicted values was calculated and analyzed for glaucoma severity, number of input visual field tests, and prediction time interval. Results: The prediction errors of the Bi-GRU model for MD, PSD, VFI, and TDV ranged from 1.20 to 1.68 dB, 0.95 to 1.16 dB, 3.64 to 4.51%, and 2.13 to 2.60 dB, respectively, depending on the number of input visual field tests. Prediction errors tended to increase as the prediction time interval increased; however, the difference was not statistically significant. As the severity of glaucoma worsened, the prediction errors significantly increased. Conclusion: In clinical practice, the Bi-GRU model can predict future visual field tests at the desired time points using three or more previous visual field tests. [ABSTRACT FROM AUTHOR]

Background and aims: Antiviral therapy (AVT) is required in patients with newly diagnosed hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), if HBV DNA is detectable. We compared the risk of recurrence according to HBV replication activity at the curative treatment of HBV-related HCC. Methods: Patients with HBV-related HCC who underwent surgical resection or radiofrequency ablation between 2013 and 2018 were enrolled in this retrospective cohort study. Patients were categorized into two groups according to HBV replication activity at the curative treatment of HBV-related HCC (group 1: patients who met the AVT indication for HBV-related HCC due to detectable HBV DNA but did not meet the AVT indication if without HCC; group 2: patients who met the AVT indication, regardless of HCC). Results: In the entire cohort (n = 911), HCC recurred in 303 (33.3%) patients during a median follow-up of 4.7 years. After multivariate adjustment, group 2 showed a statistically similar risk of HCC recurrence (adjusted hazard ratio [aHR] = 1.18, P = 0.332) compared to that of group 1. In addition, group 2 showed statistically similar risks of early (< 2 years; aHR = 1.31) and late (≥ 2 years; aHR = 0.83) recurrence than that of group 1 (all P>0.05). Propensity score matching and inverse probability of treatment weighting analysis also yielded similar risks of HCC recurrence between the two groups (all P>0.05, log-rank tests). Conclusions: The risk of HCC recurrence in patients who received curative treatment for newly diagnosed HBV-related HCC was similar regardless of HBV replication activity, if AVT was properly initiated. [ABSTRACT FROM AUTHOR]

Identifying causal sentences from nuclear incident reports is essential for advancing nuclear safety research and applications. Nonetheless, accurately locating and labeling causal sentences in text data is challenging, and might benefit from the usage of automated techniques. In this paper, we introduce LERCause, a labeled dataset combined with labeling methods meant to serve as a foundation for the classification of causal sentences in the domain of nuclear safety. We used three BERT models (BERT, BioBERT, and SciBERT) to 10,608 annotated sentences from the Licensee Event Report (LER) corpus for predicting sentence labels (Causal vs. non-Causal). We also used a keyword-based heuristic strategy, three standard machine learning methods (Logistic Regression, Gradient Boosting, and Support Vector Machine), and a deep learning approach (Convolutional Neural Network; CNN) for comparison. We found that the BERT-centric models outperformed all other tested models in terms of all evaluation metrics (accuracy, precision, recall, and F1 score). BioBERT resulted in the highest overall F1 score of 94.49% from the ten-fold cross-validation. Our dataset and coding framework can provide a robust baseline for assessing and comparing new causal sentences extraction techniques. As far as we know, our research breaks new ground by leveraging BERT-centric models for causal sentence classification in the nuclear safety domain and by openly distributing labeled data and code to enable reproducibility in subsequent research. [ABSTRACT FROM AUTHOR]

Background/aims: Autoimmune hepatitis (AIH) is characterized by the presence of auto-antibodies and high blood immunoglobulin G (IgG) levels. In this study, the line immunoassay (LIA) was designed to assess various autoantibodies. Methods: In total, 1371 patients who underwent autoimmune liver disease antibody testing between July 2019 and November 2022 were enrolled. Autoantibodies including antinuclear antibody (ANA) and anti-mitochondrial antibody (AMA) were tested, and clinical data were collected. Statistical analyses were performed by categorizing the data based on diagnosis and IgG quantification separately. A scoring system was applied to identify individuals with AIH. Patients were also classified into the AIH and non-AIH groups. Results: The positivity rate for ANA was 80.2% in the AIH group. The IgG-high group had a high likelihood of the presence of detectable autoantibodies, with anti-Ro-52 being the most frequently detected antibody using LIA. The "Consider AIH" and "AMA" groups had 3–4 times more patients in the IgG-high group than in the "Not Considered" group. Conclusions: Among autoantibodies, the prevalence of ANA was the highest. As per LIA results, anti-Ro-52 was the most prevalent. AIH cannot be diagnosed based on IgG levels alone and must be distinguished via autoantibody testing. Therefore, extensive testing, including autoantibodies, IgG, ANA, and liver enzyme levels, will help accurately diagnose AIH. [ABSTRACT FROM AUTHOR]

Background/purpose: Distal radius fractures (DRFs) account for approximately 18% of fractures in patients 65 years and older. While plain radiographs are standard, the value of high-resolution computed tomography (CT) for detailed imaging crucial for diagnosis, prognosis, and intervention planning, and increasingly recognized. High-definition 3D reconstructions from CT scans are vital for applications like 3D printing in orthopedics and for the utility of mobile C-arm CT in orthopedic diagnostics. However, concerns over radiation exposure and suboptimal image resolution from some devices necessitate the exploration of advanced computational techniques for refining CT imaging without compromising safety. Therefore, this study aims to utilize conditional Generative Adversarial Networks (cGAN) to improve the resolution of 3 mm CT images (CT enhancement). Methods: Following institutional review board approval, 3 mm-1 mm paired CT data from 11 patients with DRFs were collected. cGAN was used to improve the resolution of 3 mm CT images to match that of 1 mm images (CT enhancement). Two distinct methods were employed for training and generating CT images. In Method 1, a 3 mm CT raw image was used as input with the aim of generating a 1 mm CT raw image. Method 2 was designed to emphasize the difference value between the 3 mm and 1 mm images; using a 3 mm CT raw image as input, it produced the difference in image values between the 3 mm and 1 mm CT scans. Both quantitative metrics, such as peak signal-to-noise ratio (PSNR), mean squared error (MSE), and structural similarity index (SSIM), and qualitative assessments by two orthopedic surgeons were used to evaluate image quality by assessing the grade (1~4, which low number means high quality of resolution). Results: Quantitative evaluations showed that our proposed techniques, particularly emphasizing the difference value in Method 2, consistently outperformed traditional approaches in achieving higher image resolution. In qualitative evaluation by two clinicians, images from method 2 showed better quality of images (grade: method 1, 2.7; method 2, 2.2). And more choice was found in method 2 for similar image with 1 mm slice image (15 vs 7, p = 201). Conclusion: In our study utilizing cGAN for enhancing CT imaging resolution, the authors found that the method, which focuses on the difference value between 3 mm and 1 mm images (Method 2), consistently outperformed. [ABSTRACT FROM AUTHOR]

Background: Although sonication is a valuable diagnostic tool for periprosthetic joint infections (PJI), it is not commonly utilized. We analyzed sonicate and intraoperative tissue culture results obtained from three hospitals to define the microbial etiology of PJIs in Korea. Furthermore, we investigated necessity of conducting regular fungal and mycobacterial cultures. Methods: We retrospectively analyzed data for patients with suspected orthopedic-related infections between 2017 and 2022, who had undergone prostheses removal surgery. We included 193 patients with suspected PJIs, and bacterial (n = 193), fungal (n = 193), and mycobacterial (n = 186) cultures were conducted on both sonicate and intraoperative tissue samples. The diagnosis of PJI was based on the European Bone and Joint Infection Society (EBJIS) criteria. Results: Out of 193 patients, 121 (62.7%) had positive sonicate cultures, while 112 (58.0%) had positive periprosthetic tissue cultures. According to EBJIS criteria, a total of 181 patients were diagnosed with PJI, and 141 patients received microbiological confirmation through sonicate fluid culture or tissue culture. Of the 181 patients, 28 were classified with acute PJI (within 3 months of implantation) and 153 with chronic PJI. Among 141 patients, staphylococci were the most common organisms, accounting for 51.8% of cases, followed by Gram-negative organisms (15.6%), fungus (8.5%), and mycobacteria (3.5%). Nearly 91.7% of fungal isolates were Candida species, which also grew in bacterial cultures. In total, 11 cases cultured positive only in tissue culture, whereas 20 cases cultured positive only in sonicate culture. The antibiotic treatment plans were adjusted according to culture results. Conclusions: Utilizing sonicate culture has greatly assisted in identifying pathogens responsible for chronic indolent PJIs, allowing suitable antimicrobial treatment. Based on few cases involving non-Candida and mycobacterial infections, it appears that routine fungal and mycobacterial cultures may not be necessary. [ABSTRACT FROM AUTHOR]