Tolerance is established in polyclonal CD4(+) T cells by distinct mechanisms, according to self-peptide expression patterns.

Studies of repertoires of mouse monoclonal CD4(+) T cells have revealed several mechanisms of self-tolerance; however, which mechanisms operate in normal repertoires is unclear. Here we studied polyclonal CD4(+) T cells specific for green fluorescent protein expressed in various organs, which allowed us to determine the effects of specific expression patterns on the same epitope-specific T cells. Peptides presented uniformly by thymic antigen-presenting cells were tolerated by clonal deletion, whereas peptides excluded from the thymus were ignored. Peptides with limited thymic expression induced partial clonal deletion and impaired effector T cell potential but enhanced regulatory T cell potential. These mechanisms were also active for T cell populations specific for endogenously expressed self antigens. Thus, the immunotolerance of polyclonal CD4(+) T cells was maintained by distinct mechanisms, according to self-peptide expression patterns.

Integrative Metabolomics Differentiate Coronary Artery Disease, Peripheral Artery Disease, and Venous Thromboembolism Risks.

BACKGROUND: Arterial and venous cardiovascular conditions, such as coronary artery disease (CAD), peripheral artery disease (PAD), and venous thromboembolism (VTE), are genetically correlated. Interrogating underlying mechanisms may shed light on disease mechanisms. In this study, we aimed to identify (1) epidemiological and (2) causal, genetic relationships between metabolites and CAD, PAD, and VTE. METHODS: We used metabolomic data from 95 402 individuals in the UK Biobank, excluding individuals with prevalent cardiovascular disease. Cox proportional-hazards models estimated the associations of 249 metabolites with incident disease. Bidirectional 2-sample Mendelian randomization (MR) estimated the causal effects between metabolites and outcomes using genome-wide association summary statistics for metabolites (n=118 466 from the UK Biobank), CAD (n=184 305 from CARDIoGRAMplusC4D 2015), PAD (n=243 060 from the Million Veterans Project), and VTE (n=650 119 from the Million Veterans Project). Multivariable MR was performed in subsequent analyses. RESULTS: We found that 196, 115, and 74 metabolites were associated (P<0.001) with CAD, PAD, and VTE, respectively. Further interrogation of these metabolites with MR revealed 94, 34, and 9 metabolites with potentially causal effects on CAD, PAD, and VTE, respectively. There were 21 metabolites common to CAD and PAD and 4 common to PAD and VTE. Many putatively causal metabolites included lipoprotein traits with heterogeneity across different sizes and lipid subfractions. Small VLDL (very-low-density lipoprotein) particles increased the risk for CAD while large VLDL particles decreased the risk for VTE. We identified opposing directions of CAD and PAD effects for cholesterol and triglyceride concentrations within HDLs (high-density lipoproteins). Subsequent sensitivity analyses including multivariable MR revealed several metabolites with robust, potentially causal effects of VLDL particles on CAD. CONCLUSIONS: While common vascular conditions are associated with overlapping metabolomic profiles, MR prioritized the role of specific lipoprotein species for potential pharmacological targets to maximize benefits in both arterial and venous beds.

Regulatory variants in TCF7L2 are associated with thoracic aortic aneurysm.

Thoracic aortic aneurysm (TAA) is characterized by dilation of the aortic root or ascending/descending aorta. TAA is a heritable disease that can be potentially life threatening. While 10%-20% of TAA cases are caused by rare, pathogenic variants in single genes, the origin of the majority of TAA cases remains unknown. A previous study implicated common variants in FBN1 with TAA disease risk. Here, we report a genome-wide scan of 1,351 TAA-affected individuals and 18,295 control individuals from the Cardiovascular Health Improvement Project and Michigan Genomics Initiative at the University of Michigan. We identified a genome-wide significant association with TAA for variants within the third intron of TCF7L2 following replication with meta-analysis of four additional independent cohorts. Common variants in this locus are the strongest known genetic risk factor for type 2 diabetes. Although evidence indicates the presence of different causal variants for TAA and type 2 diabetes at this locus, we observed an opposite direction of effect. The genetic association for TAA colocalizes with an aortic eQTL of TCF7L2, suggesting a functional relationship. These analyses predict an association of higher expression of TCF7L2 with TAA disease risk. In vitro, we show that upregulation of TCF7L2 is associated with BCL2 repression promoting vascular smooth muscle cell apoptosis, a key driver of TAA disease.

Socioeconomic deprivation is associated with worse patient and graft survival following adult liver transplantation.

The impact of social determinants of health on adult liver transplant recipient outcomes is not clear at a national level. Further understanding of the impact of social determinants of health on patient outcomes can inform effective, equitable health care delivery. Unadjusted and multivariable models were used to analyze the Scientific Registry of Transplant Recipients to evaluate the association between the Social Deprivation Index (SDI) based on the liver transplant recipient's residential location and patient and graft survival. We included adult recipients between January 1, 2008 and December 1, 2021. Patient and graft survival were lower in adults living in areas with deprivation scores above the median. Five-year patient and graft survival were 78.7% and 76.5%, respectively, in the cohort above median SDI compared to 80.5% and 78.3% below median SDI. Compared to the recipients in low-deprivation residential areas, recipients residing in the highest deprivation (SDI quintile = 5) cohort had 6% higher adjusted risk of mortality (adjusted hazard ratio = 1.06, 95% CI: 1.01-1.13) and 6% higher risk of graft failure (adjusted hazard ratio = 1.06, 95% CI: 1.001-1.11). The increased risks for recipients residing in more vulnerable residential areas were higher (adjusted hazard ratio = 1.11, 95% CI: 1.03-1.20 for both death and graft loss) following the first year after transplantation. Importantly, the overall risk for graft loss associated with SDI was not linear but instead accelerated above the median level of deprivation. In the United States, social determinants of health, as reflected by residential distress, significantly impacts 5-year patient and graft survival. The overall effect of residential deprivation modest, and importantly, results illustrate they are more strongly associated with longer-term follow-up and accelerate at higher deprivation levels. Further research is needed to evaluate effective interventions and policies to attenuate disparities in outcomes among recipients in highly disadvantaged areas.

Psychosocial evaluation of living liver donors-State of current practices in the United States.

We surveyed living donor liver transplant programs in the United States to describe practices in the psychosocial evaluation of living donors focused on (1) composition of psychosocial team; (2) domains, workflow, and tools of the psychosocial assessment; (3) absolute and relative mental health-related contraindications to donation; and (4) postdonation psychosocial follow-up. We received 52 unique responses, representing 33 of 50 (66%) of active living donor liver transplant programs. Thirty-one (93.9%) provider teams included social workers, 22 (66.7%) psychiatrists, and 14 (42.4%) psychologists. Validated tools were rarely used, but domains assessed were consistent. Respondents rated active alcohol (93.8%), cocaine (96.8%), and opioid (96.8%) use disorder, as absolute contraindications to donation. Active suicidality (97%), self-injurious behavior (90.9%), eating disorders (87.9%), psychosis (84.8%), nonadherence (71.9%), and inability to cooperate with the evaluation team (78.1%) were absolute contraindications to donation. There were no statistically significant differences in absolute psychosocial contraindications to liver donation between geographical areas or between large and small programs. Programs conduct postdonation psychosocial follow-up (57.6%) or screening (39.4%), but routine follow-up of declined donors is rarely conducted (15.8%). Psychosocial evaluation of donor candidates is a multidisciplinary process. The structure of the psychosocial evaluation of donors is not uniform among programs though the domains assessed are consistent. Psychosocial contraindications to living liver donation vary among the transplant programs. Mental health follow-up of donor candidates is not standardized.

Impact of Standardized Multidisciplinary Critical Care Training on Confidence with Critical Illness and Attitudes Towards Interprofessional Education and Multidisciplinary Care.

INTRODUCTION: The Fundamental Critical Care Support Course (FCCS) is a standardized multidisciplinary program designed to educate participants on the basics of identification and management of patients with critical illness. Our objective was to evaluate the effect of FCCS participation on confidence in the assessment and management of critically ill patients and attitudes towards multidisciplinary education and interprofessional care in a multidisciplinary group of participants. METHODS: Participants enrolled in the FCCS course from May 2018 to November 2019 were solicited to participate in a series of surveys evaluating their course experience and confidence in critical care. Attitudes towards multidisciplinary education and interprofessional care were evaluated using the Student Perceptions of Interprofessional Clinical Education-Revised Instrument version 2 (SPICE-R2) tool. A prospective pre- and post-design with a self-report survey including retrospective pre-training assessment and a 3-month follow-up was conducted. Statistical analysis was performed using descriptive statics and non-parametric methods. RESULTS: 321 (97.9%) of the course participants enrolled in the study and completed the confidence survey and SPICE-R2 tool pre-course. Nurses (113, 35.4%) and physicians (110, 34.4%) made up the largest groups of participants, although physician assistants and paramedics were also well represented. Confidence in recognition and management of critical illness significantly improved across all studied domains after course completion, with the mean total confidence score improving from 32.96 pre-course to 41.10 post-course, P < 0.001. Attitudes towards multidisciplinary education and interprofessional care also improved (mean score 41.37 pre-course vs 42.71 post-course, P < 0.001), although pre-course numbers were higher than expected which limited the significance to only certain domains. DISCUSSION: In a multidisciplinary group, completion of FCCS training led to increased confidence in all aspects of critical illness measured. A modest increase in attitudes regarding multidisciplinary education and interprofessional care was also demonstrated. Further study is needed to assess whether this increased confidence translates to improvements in patient care and outcomes.

An atlas of posttranslational modifications on RNA binding proteins.

RNA structure and function are intimately tied to RNA binding protein recognition and regulation. Posttranslational modifications are chemical modifications which can control protein biology. The role of PTMs in the regulation RBPs is not well understood, in part due to a lacking analysis of PTM deposition on RBPs. Herein, we present an analysis of posttranslational modifications (PTMs) on RNA binding proteins (RBPs; a PTM RBP Atlas). We curate published datasets and primary literature to understand the landscape of PTMs and use protein-protein interaction data to understand and potentially provide a framework for understanding which enzymes are controlling PTM deposition and removal on the RBP landscape. Intersection of our data with The Cancer Genome Atlas also provides researchers understanding of mutations that would alter PTM deposition. Additional characterization of the RNA-protein interface provided from in-cell UV crosslinking experiments provides a framework for hypotheses about which PTMs could be regulating RNA binding and thus RBP function. Finally, we provide an online database for our data that is easy to use for the community. It is our hope our efforts will provide researchers will an invaluable tool to test the function of PTMs controlling RBP function and thus RNA biology.

Chronic Disease Prevalence in the US: Sociodemographic and Geographic Variations by Zip Code Tabulation Area.

Introduction: We examined the geographic distribution and sociodemographic and economic characteristics of chronic disease prevalence in the US. Understanding disease prevalence and its impact on communities is crucial for effective public health interventions. Methods: Data came from the American Community Survey, the American Hospital Association Survey, and the Centers for Disease Control and Prevention's PLACES. We used quartile thresholds for 10 chronic diseases to assess chronic disease prevalence by Zip Code Tabulation Areas (ZCTAs). ZCTAs were scored from 0 to 20 based on their chronic disease prevalence quartile. Three prevalence categories were established: least prevalent (score ≤6), moderately prevalent (score 7-13), and highest prevalence (score ≥14). Community characteristics were compared across categories and spatial analyses to identify clusters of ZCTAs with high disease prevalence. Results: Our study showed a high prevalence of chronic disease in the southeastern region of the US. Populations in ZCTAs with the highest prevalence showed significantly greater socioeconomic disadvantages (ie, lower household income, lower home value, lower educational attainment, and higher uninsured rates) and barriers to health care access (lower percentage of car ownership and longer travel distances to hospital-based intensive care units, emergency departments, federally qualified health centers, and pharmacies) compared with ZCTAs with the lowest prevalence. Conclusion: Socioeconomic disparities and health care access should be addressed in communities with high chronic disease prevalence. Carefully directed resource allocation and interventions are necessary to reduce the effects of chronic disease on these communities. Policy makers and clinicians should prioritize efforts to reduce chronic disease prevalence and improve the overall health and well-being of affected communities throughout the US.

Dialysis More Available Than Patient Education in Counties With High Diabetes Prevalence.

Introduction: Poorly controlled diabetes is a principal cause of end stage renal disease (ESRD), generating an estimated 44% of new cases. Diabetes self-management education and support (DSMES) has been documented to reduce adverse outcomes such as ESRD. Helping patients better manage their condition could ultimately reduce ESRD prevalence. Methods: We compared the county-level availability of DSMES and dialysis as of November 2022 sorted by the estimated prevalence of diabetes among residents aged 18 years or older. The locations of DSMES programs and ESRD dialysis facilities were obtained from 2 professional organizations and the Centers for Medicare & Medicade Services. Estimated diabetes prevalence was obtained from the Centers for Disease Control and Prevention's PLACES data set. Counties were considered to have high diabetes prevalence if they fell into the top quartile for diabetes prevalence in 2019 (≥14.4% of adults). Analyses were conducted in 2023. Results: DSMES was available in 41.0% of counties but in only 20.7% of counties with high diabetes prevalence versus 47.9% of low prevalence counties. Dialysis facilities were present in 59.2% of all counties, in 52.8% of all high diabetes prevalence counties, and in 61.4% of other counties. DSMES availability was linked to the presence of a hospital in the county, with only 6.3% of counties without a hospital offering the service. Implications: DSMES could play a role in reducing the prevalence of ESRD. Public health professionals need to be aware of the differing levels of local availability of this service and work to develop partnerships to provide DSMES in high-prevalence areas not currently served.

An optimized chemical-genetic method for cell-specific metabolic labeling of RNA.

Tissues and organs are composed of diverse cell types, which poses a major challenge for cell-type-specific profiling of gene expression. Current metabolic labeling methods rely on exogenous pyrimidine analogs that are only incorporated into RNA in cells expressing an exogenous enzyme. This approach assumes that off-target cells cannot incorporate these analogs. We disprove this assumption and identify and characterize the enzymatic pathways responsible for high background incorporation. We demonstrate that mammalian cells can incorporate uracil analogs and characterize the enzymatic pathways responsible for high background incorporation. To overcome these limitations, we developed a new small molecule-enzyme pair consisting of uridine/cytidine kinase 2 and 2'-azidouridine. We demonstrate that 2'-azidouridine is only incorporated in cells expressing uridine/cytidine kinase 2 and characterize selectivity mechanisms using molecular dynamics and X-ray crystallography. Furthermore, this pair can be used to purify and track RNA from specific cellular populations, making it ideal for high-resolution cell-specific RNA labeling. Overall, these results reveal new aspects of mammalian salvage pathways and serve as a new benchmark for designing, characterizing and evaluating methodologies for cell-specific labeling of biomolecules.

Measuring and addressing health equity: an assessment of cancer center designation requirements.

PURPOSE: By requiring specific measures, cancer endorsements (e.g., accreditations, designations, certifications) promote high-quality cancer care. While 'quality' is the defining feature, less is known about how these endorsements consider equity. Given the inequities in access to high-quality cancer care, we assessed the extent to which equity structures, processes, and outcomes were required for cancer center endorsements. METHODS: We performed a content analysis of medical oncology, radiation oncology, surgical oncology, and research hospital endorsements from the American Society of Clinical Oncology (ASCO), American Society of Radiation Oncology (ASTRO), American College of Surgeons Commission on Cancer (CoC), and the National Cancer Institute (NCI), respectively. We analyzed requirements for equity-focused content and compared how each endorsing body included equity as a requirement along three axes: structures, processes, and outcomes. RESULTS: ASCO guidelines centered on processes assessing financial, health literacy, and psychosocial barriers to care. ASTRO guidelines related to language needs and processes to address financial barriers. CoC equity-related guidelines focused on processes addressing financial and psychosocial concerns of survivors, and hospital-identified barriers to care. NCI guidelines considered equity related to cancer disparities research, inclusion of diverse groups in outreach and clinical trials, and diversification of investigators. None of the guidelines explicitly required measures of equitable care delivery or outcomes beyond clinical trial enrollment. CONCLUSION: Overall, equity requirements were limited. Leveraging the influence and infrastructure of cancer quality endorsements could enhance progress toward achieving cancer care equity. We recommend that endorsing organizations 1) require cancer centers to implement processes for measuring and tracking health equity outcomes and 2) engage diverse community stakeholders to develop strategies for addressing discrimination.

Equitable implementation of lung cancer screening: avoiding its potential to mirror existing inequities among people who use tobacco.

PURPOSE: Lung cancer is the leading cause of cancer death, but the advent of lung cancer screening using low-dose computed tomography offers a tremendous opportunity to improve lung cancer outcomes. Unfortunately, implementation of lung cancer screening has been hampered by substantial barriers and remains suboptimal. Specifically, the commentary emphasizes the intersectionality of smoking history and several important sociodemographic characteristics and identities that should inform lung cancer screening outreach and engagement efforts, including socioeconomic considerations (e.g., health insurance status), racial and ethnic identity, LGBTQ + identity, mental health history, military experience/veteran status, and geographic residence in addressing specific community risk factors and future interventions in efforts to make strides toward equitable lung cancer screening. METHODS: Members of the Equitable Implementation of Lung Cancer Screening Interest Group with the Cancer Prevention and Control Network (CPCRN) provide a critical commentary based on existing literature regarding smoking trends in the US and lung cancer screening uptake to propose opportunities to enhance implementation and support equitable distribution of the benefits of lung cancer screening. CONCLUSION: The present commentary utilizes information about historical trends in tobacco use to highlight opportunities for targeted outreach efforts to engage communities at high risk with information about the lung cancer screening opportunity. Future efforts toward equitable implementation of lung cancer screening should focus on multi-level implementation strategies that engage and work in concert with community partners to co-create approaches that leverage strengths and reduce barriers within specific communities to achieve the potential of lung cancer screening.

Effect of rurality and travel distance on contralateral prophylactic mastectomy for unilateral breast cancer.

PURPOSE: Despite lack of survival benefit, demand for contralateral prophylactic mastectomy (CPM) to treat unilateral breast cancer remains high. High uptake of CPM has been demonstrated in Midwestern rural women. Greater travel distance for surgical treatment is associated with CPM. Our objective was to examine the relationship between rurality and travel distance to surgery with CPM. METHODS: Women diagnosed with stages I-III unilateral breast cancer between 2007 and 2017 were identified using the National Cancer Database. Logistic regression was used to model likelihood of CPM based on rurality, proximity to metropolitan centers, and travel distance. A multinomial logistic regression model compared factors associated with CPM with reconstruction versus other surgical options. RESULTS: Both rurality (OR 1.10, 95% CI 1.06-1.15 for non-metro/rural vs. metro) and travel distance (OR 1.37, 95% CI 1.33-1.41 for those who traveled 50 + miles vs. < 30 miles) were independently associated with CPM. For women who traveled 30 + miles, odds of receiving CPM were highest for non-metro/rural women (OR 1.33 for 30-49 miles, OR 1.57 for 50 + miles; reference: metro women traveling < 30 miles). Non-metro/rural women who received reconstruction were more likely to undergo CPM regardless of travel distance (ORs 1.11-1.21). Both metro and metro-adjacent women who received reconstruction were more likely to undergo CPM only if they traveled 30 + miles (ORs 1.24-1.30). CONCLUSION: The impact of travel distance on likelihood of CPM varies by patient rurality and receipt of reconstruction. Further research is needed to understand how patient residence, travel burden, and geographic access to comprehensive cancer care services, including reconstruction, influence patient decisions regarding surgery.

Prioritizing rural populations in state comprehensive cancer control plans: a qualitative assessment.

PURPOSE: The Centers for Disease Control and Prevention's National Comprehensive Cancer Control Program (NCCCP) requires that states develop comprehensive cancer control (CCC) plans and recommends that disparities related to rural residence are addressed in these plans. The objective of this study was to explore rural partner engagement and describe effective strategies for incorporating a rural focus in CCC plans. METHODS: States were selected for inclusion using stratified sampling based on state rurality and region. State cancer control leaders were interviewed about facilitators and barriers to engaging rural partners and strategies for prioritizing rural populations. Content analysis was conducted to identify themes across states. RESULTS: Interviews (n = 30) revealed themes in three domains related to rural inclusion in CCC plans. The first domain (barriers) included (1) designing CCC plans to be broad, (2) defining "rural populations," and (3) geographic distance. The second domain (successful strategies) included (1) collaborating with rural healthcare systems, (2) recruiting rural constituents, (3) leveraging rural community-academic partnerships, and (4) working jointly with Native nations. The third domain (strategies for future plan development) included (1) building relationships with rural communities, (2) engaging rural constituents in planning, (3) developing a better understanding of rural needs, and (4) considering resources for addressing rural disparities. CONCLUSION: Significant relationship building with rural communities, resource provision, and successful strategies used by others may improve inclusion of rural needs in state comprehensive cancer control plans and ultimately help plan developers directly address rural cancer health disparities.

Practice patterns of the medical evaluation of living liver donors in the United States.

Living donor liver transplantation (LDLT) can help address the growing organ shortage in the United States, yet little is known about the current practice patterns in the medical evaluation of living liver donors. We conducted a 131-question survey of all 53 active LDLT transplant programs in the United States to assess current LDLT practices. The response rate was 100%. Donor acceptance rate was 0.33 with an interquartile range of 0.33-0.54 across all centers. Areas of high intercenter agreement included minimum age cutoff of 18 years (73.6%) and the exclusion of those with greater than Class 1 obesity (body mass index, 30.0-34.9 m/kg 2 ) (88.4%). Diabetes mellitus was not an absolute exclusion at most centers (61.5%). Selective liver biopsies were performed for steatosis or iron overload on imaging (67.9% and 62.3%, respectively) or for elevated liver enzymes (60.4%). Steatohepatitis is considered an exclusion at most centers (84.9%). The most common hypercoagulable tests performed were factor V Leiden (FVL) (88.5%), protein C (73.1%), protein S (71.2%), antithrombin III (71.2%) and prothrombin gene mutation (65.4%). At 41.5% of centers, donors were allowed to proceed with donation with FVL heterozygote status. Most programs discontinue oral contraceptive pills at least 28 days prior to surgery. At most centers, the need for cardiovascular ischemic risk testing is based on age (73.6%) and the presence of one or more cardiac risk factors (68.0%). Defining areas of practice consensus and variation underscores the need for data generation to develop evidence-based guidance for the evaluation and risk assessment of living liver donors.

Living donor liver transplant candidate and donor selection and engagement: Meeting report from the living donor liver transplant consensus conference.

INTRODUCTION: Living donor liver transplantation (LDLT) is a promising option for mitigating the deceased donor organ shortage and reducing waitlist mortality. Despite excellent outcomes and data supporting expanding candidate indications for LDLT, broader uptake throughout the United States has yet to occur. METHODS: In response to this, the American Society of Transplantation hosted a virtual consensus conference (October 18-19, 2021), bringing together relevant experts with the aim of identifying barriers to broader implementation and making recommendations regarding strategies to address these barriers. In this report, we summarize the findings relevant to the selection and engagement of both the LDLT candidate and living donor. Utilizing a modified Delphi approach, barrier and strategy statements were developed, refined, and voted on for overall barrier importance and potential impact and feasibility of the strategy to address said barrier. RESULTS: Barriers identified fell into three general categories: 1) awareness, acceptance, and engagement across patients (potential candidates and donors), providers, and institutions, 2) data gaps and lack of standardization in candidate and donor selection, and 3) data gaps regarding post-living liver donation outcomes and resource needs. CONCLUSIONS: Strategies to address barriers included efforts toward education and engagement across populations, rigorous and collaborative research, and institutional commitment and resources.

Impact of Sublethal Concentrations of Nitrite on Goldfish (Carassius auratus) Microbiomes.

Elevated concentrations of nitrite are toxic to fish and can cause a myriad of well documented issues. However, the effects of sublethal concentrations of nitrite on fish health, and specifically, fish tissue microbiomes have not been studied. To test the effects of nitrite exposure, goldfish were exposed to sublethal concentrations of nitrite, 0.0 mM, 0.1 mM, and 1.0 mM, for 2 months. The bacteria in the nose, skin, gills, and water were then extracted and sequenced to identify changes to the microbial composition. The water microbiome was not significantly changed by the added nitrite; however, each of the tissue microbiomes was changed by at least one of the treatments. The skin and gill microbiomes were significantly different between the control and 1.0 mM treatment and the nose microbiome showed significant changes between the control and both the 0.1 mM and 1.0 mM treatments. Thus, sublethal concentrations of nitrite in the environment caused a shift in the fish tissue microbiomes independently of the water microbiome. These changes could lead to an increased chance of infection, disrupt organ systems, and raise the mortality rate of fish. In systems with high nitrite concentrations, like intensive aquaculture setups or polluted areas, the effects of nitrite on the microbiomes could negatively affect fish populations.

Can non-directed living liver donation help improve access to grafts and correct socioeconomic disparities in pediatric liver transplantation?

BACKGROUND: Each year, children die awaiting LT as the demand for grafts exceeds the available supply. Candidates with public health insurance are significantly less likely to undergo both deceased donor LT and D-LLD LT. ND-LLD is another option to gain access to a graft. The aim of this study was to evaluate if recipient insurance type is associated with likelihood of D-LLD versus ND-LLD LT. METHODS: The SRTR/OPTN database was reviewed for pediatric LDLT performed between January 1, 2014 (Medicaid expansion era) and December 31, 2019 at centers that performed ≥1 ND-LLD LDLT during the study period. A multivariable logistic regression was performed to assess relationship between type of living donor (directed vs. non-directed) and recipient insurance. RESULTS: Of 299 pediatric LDLT, 46 (15%) were from ND-LLD performed at 18 transplant centers. Fifty-nine percent of ND-LLD recipients had public insurance in comparison to 40% of D-LLD recipients (p = .02). Public insurance was associated with greater odds of ND-LLD in comparison to D-LLD upon multivariable logistic regression (OR 2.37, 95% CI 1.23-4.58, p = .01). CONCLUSIONS: ND-LLD allows additional children to receive LTs and may help address some of the socioeconomic disparity in pediatric LDLT, but currently account for only a minority of LDLT and are only performed at a few institutions. Initiatives to improve access to both D-LLD and ND-LLD transplants are needed.

Factors associated with vulvar cancer from 2005 to 2021 in Togo, sub-Saharan Africa.

BACKGROUND: vulvar cancer, once predominantly diagnosed in older women, is increasingly being diagnosed in younger individuals, due to Human Papillomavirus (HPV) infection. Our study aimed to describe the epidemiological and histopathological aspects of vulvar cancer in Togo and its associated factors. METHODS: This was a cross-sectional study, conducted on vulvar cancer cases histologically diagnosed at the Pathological Laboratory of Lomé over a period of 17-years (2005-2021). Parameters investigated included age, occupation, risk factors, sample nature, macroscopic tumor aspects, histological types, therapeutic intervenions, and prognostic outcomes. RESULTS: A total of 32 cases of vulvar cancer were collected, yieding an annual frequency of 1.88 cases. The average age of the patients was 48±14.12 years with extremes of 27 years and 82 years. Housewives accounted for the largest proportion of cases (37.5%). Among the 32 cases, 27 had identifiable risk factors, with HPV infection being the most prevalentr (33.3%). The ulcero-budding aspect was most frequently observed, and squamous cell carcinoma was the most common histological type, with the majority being well differentiated (89.3%). Statistically significant associations were found between risk factors and histological types, risk factors and degrees of differentiation, as well as between histological types and good differentiation of vulvar cancers. The 3-year survival was estimated at 78.13%. CONCLUSION: The incidence of vulvar cancer is increasing in Togo, particularly among young, primarily due to HPV infection.

Diverse functional elements in RNA predicted transcriptome-wide by orthogonal RNA structure probing.

RNA molecules can fold into complex structures and interact with trans-acting factors to control their biology. Recent methods have been focused on developing novel tools to measure RNA structure transcriptome-wide, but their utility to study and predict RNA-protein interactions or RNA processing has been limited thus far. Here, we extend these studies with the first transcriptome-wide mapping method for cataloging RNA solvent accessibility, icLASER. By combining solvent accessibility (icLASER) with RNA flexibility (icSHAPE) data, we efficiently predict RNA-protein interactions transcriptome-wide and catalog RNA polyadenylation sites by RNA structure alone. These studies showcase the power of designing novel chemical approaches to studying RNA biology. Further, our study exemplifies merging complementary methods to measure RNA structure inside cells and its utility for predicting transcriptome-wide interactions that are critical for control of and regulation by RNA structure. We envision such approaches can be applied to studying different cell types or cells under varying conditions, using RNA structure and footprinting to characterize cellular interactions and processing involving RNA.