bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Inflammatory Bowel Disease in Children With Juvenile Idiopathic Arthritis Treated With Biologics
Authors: Broekaert Ilse J. , Klein Ariane , Windschall Daniel , Rogalski Betina , Weller-Heinemann Frank , Oommen Prasad , Küster Michael , Foeldvari Ivan , Minden Kirsten , Hospach Anton , Hufnagel Markus , Berger Thomas , Geikowski Til , Quietzsch Jürgen , Horneff Gerd
Published: November 2022

Objective:

The aim of our study was to describe the distinct features of inflammatory bowel disease (IBD) in juvenile idiopathic arthritis (JIA) patients and to identify risk factors for its development.

Methods:

Data from the German biologics in pediatric rheumatology registry (Biologika in der Kinderrheumatologie) collected between 2001 and 2021 were analyzed retrospectively.

Results:

In 5009 JIA patients, 28 developed confirmed IBD before the age of 18 years: 23 (82.1%) with Crohn disease (CD), 4 (14.3%) with ulcerative colitis (UC), and 1 (3.6%) with IBD-unclassified (IBD-U). The incident rate of IBD during 20 years of observation was 0.56% (0.46% for CD, 0.08% for UC, and 0.02% for IBD-U), of whom 20.3% were HLA-B27 positive, 25% had enthesitis-related arthritis, and 14.3% psoriatic arthritis. Within 90 days before IBD diagnosis, 82.1% (n = 23) received treatment with etanercept (ETA), 39.3% (n = 11) non-steroidal anti-inflammatory drugs, 17.9% (n = 5) systemic corticosteroids, 8 (28.6%) methotrexate (MTX), 14.3% (n = 4) sulfasalazine, 10.7% (n = 3) leflunomide, and 3.6% (n = 1) adalimumab and infliximab, respectively. The incidence of IBD was lower in patients treated with MTX, but higher in patients treated with ETA except if ETA was combined with MTX. Also in patients on leflunomide or sulfasalazine, the IBD incidence was higher.

Conclusions:

In our JIA cohort, an increased IBD incidence is observed compared to the general population, and the ratio of CD to UC is markedly higher hinting at a distinct phenotype of IBD. Pretreatment with MTX seems to be protective. Treatment with ETA does not prevent IBD development and JIA patients treated with leflunomide and sulfasalazine may be at an increased risk for IBD development.
Dolutegravir-containing HIV therapy reversibly alters mitochondrial health and morphology in cultured human fibroblasts and peripheral blood mononuclear cells
Authors: Ajaykumar Abhinav , Caloren Loïc C. , Povshedna Tetiana , Hsieh Anthony Y.Y. , Zakaria Aya , Cai Renying , Smith Marie-Soleil R. , Thompson Connor A.H. , Becquart Pierre , Uday Prakruti , Pattanshetti Rutuja , Quandt Jacqueline A. , Wong Judy M.Y. , Côté Hélène C.F.
Published: November 2022

Objectives:

Given the success of combination antiretroviral therapy (cART) in treating HIV viremia, drug toxicity remains an area of interest in HIV research. Despite newer integrase strand transfer inhibitors (InSTIs), such as dolutegravir (DTG) and raltegravir (RAL), having excellent clinical tolerance, there is emerging evidence of off-target effects and toxicities. Although limited in number, recent reports have highlighted the vulnerability of mitochondria to these toxicities. The aim of the present study is to quantify changes in cellular and mitochondrial health following exposure to current cART regimens at pharmacological concentrations. A secondary objective is to determine whether any cART-associated toxicities would be modulated by human telomerase reverse transcriptase (hTERT).

Methods:

We longitudinally evaluated markers of cellular (cell count, apoptosis), and mitochondrial health [mitochondrial reactive oxygen species (mtROS), membrane potential (MMP) and mass (mtMass)] by flow cytometry in WI-38 human fibroblast with differing hTERT expression/localization and peripheral blood mononuclear cells. This was done after 9 days of exposure to, and 6 days following the removal of, seven current cART regimens, including three that contained DTG. Mitochondrial morphology was assessed by florescence microscopy and quantified using a recently developed deep learning-based pipeline.

Results:

Exposure to DTG-containing regimens increased apoptosis, mtROS, mtMass, induced fragmented mitochondrial networks compared with non-DTG-containing regimens, including a RAL-based combination. These effects were unmodulated by telomerase expression. All effects were fully reversible following removal of drug pressure.

Conclusion:

Taken together, our observations indicate that DTG-containing regimens negatively impact cellular and mitochondrial health and may be more toxic to mitochondria, even among the generally well tolerated InSTI-based cART.
Case volume and rate are associated with outcomes in geriatric trauma: A case for geriatric trauma centers?
Authors: Kojima Mitsuaki , Endo Akira , Zakhary Bishoy , Shoko Tomohisa , Firek Matthew , Coimbra Raul
Published: November 2022

BACKGROUND

Increased morbidity and mortality in geriatric trauma patients are usually due to decreased physiologic reserve and increased comorbidities. It is unclear whether geriatric trauma case volume and rates correlate with survival. We hypothesized that geriatric patients would have increased survival when treated in high-case volume and rate trauma centers.

METHODS

A retrospective cohort study was conducted using the Trauma Quality Improvement Program database between 2015 and 2019. Geriatric trauma patients (≥65 years) with severe injury (Injury Severity Score ≥16) were included. Geriatric case volume (GCV) was defined as the mean annual number of treated geriatric trauma patients, while geriatric case rate (GCR) was the mean annual number of elderly trauma patients divided by all trauma patients in each center. Trauma centers were classified into low-, medium-, and high-volume and rate facilities based on GCV and GCR. The association of GCV and GCR with in-hospital mortality and complication rates was assessed using the generalized additive model (GAM) and multivariate generalized linear mixed model adjusted for patient characteristics (age, sex, Injury Severity Score, Revised Trauma Score, and Modified Frailty Index) as fixed-effect variables and hospital characteristics as random effect variables.

RESULTS

A total of 164,818 geriatric trauma patients from 812 hospitals were included in the analysis. The GAM plots showed that the adjusted odds of in-hospital mortality decreased as GCV and the GCR increased. The generalized linear mixed model revealed that both high GCV and high GCR hospitals had lower mortality rates than low GCV and GCR hospitals (adjusted odds ratio [95% confidence interval], high GCV and high GCR centers; 0.82 [0.72–0.92] and 0.81 [0.73–0.90], respectively).

CONCLUSION

Both high geriatric trauma volume and rates were associated with decreased mortality of geriatric trauma patients. Consolidation of care for elderly patients with severe injury in specialized high-volume centers may be considered.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
DCD Hepatitis C Virus–positive Donor Livers Can Achieve Favorable Outcomes With Liver Transplantation and Are Underutilized
Authors: Myers Bryan , Bekki Yuki , Kozato Akio , Crismale James F. , Schiano Thomas D. , Florman Sander
Published: November 2022

Background.

Hepatitis C virus (HCV)–positive donors (antibody-positive [Ab+] or nucleic acid test positive [NAT+] donors) have been underutilized. The aim of this study was to evaluate the utilization of livers from HCV-positive with donation after circulatory death (DCD) and to assess outcomes in recipients of these grafts.

Methods.

Data between 2015 and 2019 were obtained from the United Network for Organ Sharing database. The utilization rates and graft survival among 8455 DCD liver and nonliver donors and 2278 adult DCD liver transplantation (LT) recipients were reviewed on the basis of donor HCV Ab/NAT status.

Results.

The utilization of Ab+/NAT– donors <40 y and Ab+/NAT+ donors ≥40 y was low than utilization of HCV-negative donors (P < 0.001). Multivariate analysis identified HCV status (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.06-2.48 in Ab+/NAT–, and OR, 1.49; 95% CI, 1.09-2.05 in Ab+/NAT+) as an independent predictor of nonutilization of liver grafts. The rate of significant liver fibrosis was comparable in Ab+/NAT– (3.5%; P = 0.84) but was higher in Ab+/NAT+ (8.7%; P = 0.03) than that in Ab–/NAT– donors. Kaplan-Meier survival curves demonstrated comparable 3-y patient survival in recipients of HCV-positive grafts compared with recipients of HCV-negative grafts (P = 0.63; 85.6% in Ab–/NAT–, 80.4% in Ab+/NAT–, and 88.7% in Ab+/NAT+).

Conclusions.

Patient and graft survival rates are similar between HCV-positive and HCV-negative DCD LT. However, HCV-positive donors are particularly underutilized for DCD LT.
Outcomes of Liver Transplantation in Patients With Preexisting Coronary Artery Disease
Authors: Reznicek Emily , Sasaki Kazunari , Montane Bryce , Sims Ariel , Beard Jonathan , Fares Maan , Sharma Vikram , Cywinski Jacek , Quintini Christiano , Aucejo Federico N. , Eghtesad Bijan , Miller Charles M. , Menon K.V. Narayanan
Published: November 2022

Background.

Advances in surgical and medical technology over the years has made liver transplantation possible for older and higher risk patients. Despite rigorous preoperative cardiac testing, cardiovascular events remain a major cause of death after orthotopic liver transplantation (OLT). However, there are little data on the outcomes of OLT in patients with preexisting coronary artery disease (CAD). This study aimed to compare all-cause and cardiovascular mortality of patients with and without history of CAD undergoing OLT.

Methods.

Six hundred ninety-three adult patients with cirrhosis underwent liver transplantation between July 2013 and December 2018 (female n = 243, male n = 450; median age 59).

Results.

During the study period of 5 y (median follow-up, 24.1 mo), 92 of 693 patients (13.3%) died. All-cause mortality in the CAD group was significantly higher than in the non-CAD group (26.7% versus 9.6%; P<0.01). Cardiovascular events accounted for 52.5% of deaths (n = 21) in patients with CAD compared with 36.5% (n = 19) in non-CAD patients. At 6 mo, patients with combined nonalcoholic steatohepatitis (NASH)/CAD had significantly worse survival than those with CAD or NASH alone (P<0.01). After 6 mo, patients with CAD alone had similar survival to those with combined NASH/CAD.

Conclusions.

Patients with preexisting CAD before liver transplantation are at higher risk of death from any cause, specifically cardiovascular-related death. This risk increases with coexisting NASH. The presence of NASH and CAD at the time of liver transplant should prompt the initiation of aggressive risk factor modification for patients with CAD.
Examining the Role for Donor-specific Antibody Testing in Simultaneous Liver-kidney Transplantation: A Single-center Analysis of Outcomes
Authors: Das Anushka , Rocque Brittany , Remulla Daphne , Raza Muhammad , Barbetta Arianna , Bangerth Sarah , Goldbeck Cameron , Maw Thin Thin , Kim Jim , Kwon Yong , Emamaullee Juliet
Published: November 2022

Background.

Simultaneous liver-kidney transplantation (SLKT) is increasingly used for patients with concurrent end-stage liver and renal disease. Emerging evidence suggests that simultaneous liver transplant can provide a tolerogenic benefit to multiorgan transplant recipients. Posttransplant donor-specific antibody (DSA) may be associated with worse outcomes; however, the role for testing DSA in SLKT is unclear.

Methods.

This study retrospectively assessed the impact of DSA on outcomes following primary SLKT at a large-volume center between 2008 and 2018. Patients were grouped by positive DSA, negative DSA, and DSA not tested, and data were obtained from our institutional database and chart review.

Results.

The cohort included 138 SLKT recipients with a mean age of 56.1 ± 9.7 y; 61.6% were male, and 55.8% were Hispanic. Overall, 62 patients were tested for DSA posttransplant, and 33 patients (23.9%) had at least 1 DSA detected. A total of 34 patients (24.6%) experienced at least 1 episode of liver rejection, and 23 patients (16.7%) experienced kidney rejection. Over 50% of patients with de novo DSA changed status during their posttransplant course. Rates of both liver and kidney rejection were slightly higher in the DSA+ group, but liver allograft, kidney allograft, and patient survival did not differ when grouped by whether DSA testing was performed or DSA positivity.

Conclusions.

These data demonstrate that SLKT is associated with excellent long-term patient and allograft survival with a relatively low rate of rejection. In our experience, testing for DSA does not impact SLKT outcomes‚ and further multicenter analyses are needed to establish standard of care.
Orchid fleck dichorhavirus movement protein shows RNA silencing suppressor activity
Authors: Oliveira Leastro Mikhail , Pallás Vicente , Sánchez-Navarro Jesús Ángel
Published: November 2022

To counteract RNA interference-mediated antiviral defence, virus genomes evolved to express proteins that inhibit this plant defence mechanism. Using six independent biological approaches, we show that orchid fleck dichorhavirus citrus strain (OFV-citrus) movement protein (MP) may act as a viral suppressor of RNA silencing (VSR). By using the alfalfa mosaic virus (AMV) RNA 3 expression vector, it was observed that the MP triggered necrosis response in transgenic tobacco leaves and increased the viral RNA (vRNA) accumulation. The use of the potato virus X (PVX) expression system revealed that the cis expression of MP increased both the severity of the PVX infection and the accumulation of PVX RNAs, further supporting that MP could act as an RNA silencing suppressor (RSS). From the analysis of the RSS-defective turnip crinkle virus (TCV), we do not find local RSS activity for MP, suggesting a link between MP suppressor activity and the prevention of systemic silencing. In the analysis of local suppressive activity using the GFP-based agroinfiltration assay in Nicotiana benthamiana (16 c line), we do not identify local RSS activity for the five OFV RNA1-encoded proteins. However, when evaluating the small interfering RNA (siRNA) accumulation, we find that the expression of MP significantly reduces the accumulation of GFP-derived siRNA. Finally, we examine whether the MP can prevent systemic silencing in 16c plants. Our findings show that MP inhibits the long-distance spread of RNA silencing, but does not affect the short-distance spread. Together, our findings indicate that MP is part of OFV’s counter-defence mechanism, acting mainly in the prevention of systemic long-distance silencing. This work presents the first report of a VSR for a member of the genus Dichorhavirus.
Aggregated eosinophils characterize airway mucus properties
Authors: Miyabe Yui , Fukuchi Mineyo , Tomizawa Hiroki , Nakamura Yuka , Jikei Mitsutoshi , Matsuwaki Yoshinori , Arima Misaki , Konno Yasunori , Moritoki Yuki , Takeda Masahide , Tanabe Naoya , Sima Hiroshi , Shiraishi Yusuke , Hirai Toyohiro , Ohta Nobuo , Takahata Junko , Matsubara Atsushi , Yamada Takechiyo , Asano Koichiro , Miyairi Isao , Melo Rossana C. N. , Weller Peter F. , Ueki Shigeharu
Published: November 2022

Uncontrolled airway mucus is associated with diverse diseases. We hypothesized that the physical characteristics of infiltrating granulocytes themselves affect the clinical properties of mucus. Surgically obtained nasal mucus from patients with eosinophilic chronic rhinosinusitis (ECRS) and neutrophil-dominant non-eosinophilic chronic rhinosinusitis (non-ECRS) was assessed in terms of computed tomography (CT) density, viscosity, water content, wettability, and granulocyte-specific proteins. In an observational study, we found that nasal mucus from patients with ECRS had significantly higher CT density, viscosity, dry weight, and hydrophobicity than mucus from patients with non-ECRS. The levels of eosinophil-specific proteins in nasal mucus correlated with its physical properties. When isolated human eosinophils and neutrophils were stimulated to induce extracellular traps followed by aggregate formation, we found that cell aggregates showed physical and pathological findings that closely resembled mucus. Co-treatment with heparin (which slenderizes the structure of eosinophil extracellular traps) and DNase efficiently induced a reduction in the viscosity and hydrophobicity of both eosinophil aggregates and eosinophilic mucus. The present study highlights the pathogenesis of mucus stasis in infiltrated granulocyte aggregates from a new perspective. The combination of DNase and heparin might be a novel therapeutic modality against pathologic viscous eosinophilic mucus.

One Sentence Summary

Intraluminal accumulation and activation of eosinophils contribute to the clinical properties of airway mucus and may serve as a therapeutic target.
Understanding the effectiveness of water, sanitation, and hygiene interventions: a counterfactual simulation approach to generalizing the outcomes of intervention trials
Authors: Brouwer Andrew F. , Zahid Mondal H. , Eisenberg Marisa C. , Arnold Benjamin F. , Ashraf Sania , Benjamin-Chung Jade , Colford John M. , Ercumen Ayse , Luby Stephen P. , Pickering Amy J. , Rahman Mahbubur , Kraay Alicia N.M. , Eisenberg Joseph N.S. , Freeman Matthew C.
Published: November 2022

Background

While water, sanitation, and hygiene (WASH) interventions can reduce diarrheal disease, many large-scale trials have not found the expected health gains for young children in low-resource settings. Evidence-based guidance is needed to inform interventions and future studies.

Objectives

We aimed to estimate how sensitive the intervention effectiveness found in the WASH Benefits Bangladesh randomized controlled trial was to underlying WASH contextual and intervention factors (e.g.., baseline disease prevalence, compliance, community coverage, efficacy) and to generalize the results of the trial other contexts or scenarios.

Methods

We developed a disease transmission model to account for transmission across multiple environmental pathways, multiple interventions (water (W), sanitation (S), hygiene (H), nutrition (N)) applied individually and in combination, adherence to interventions, and the impact of individuals not enrolled in the study. Leveraging a set of mechanistic parameter combinations fit to the WASH Benefits Bangladesh trial (n=17,187) using a Bayesian sampling approach, we simulated trial outcomes under counterfactual scenarios to estimate how changes in intervention completeness, coverage, compliance, and efficacy, as well as preexisting WASH conditions and baseline disease burden, impacted intervention effectiveness.

Results

Increasing community coverage had the greatest impact on intervention effectiveness (e.g., median increases in effectiveness of 34.0 and 45.5% points in the WSH and WSHN intervention arms when increasing coverage to 20%). The effect of community coverage on effectiveness depended on how much transmission was along pathways not modified by the interventions. Intervention effectiveness was reduced by lower levels of preexisting WASH conditions or increased baseline disease burden. Individual interventions had complementary but not synergistic effects when combined.

Discussion

To realize the expected health gains, future WASH interventions must address community coverage and transmission along pathways not traditionally covered by WASH. The effectiveness of individual-level WASH improvements will be blunted the further the community is from the high community coverage needed to achieve herd protection.
Using qPCR to compare the detection ofPlasmodium vivaxoocysts and sporozoites inAnopheles farautimosquitoes between two DNA extraction methods
Authors: Timinao Lincoln , Jamea Esther W. , Katusele Michelle , Schofield Louis , Burkot Thomas R. , Karl Stephan
Published: November 2022

Background

Currently, the gold standard to assess parasite developmental stages in mosquitoes is light microscopy. Microscopy can miss low-density infections, is time-consuming and not species-specific. This can place limitations on studies, especially when the infection status of larger mosquito populations is important and studies are done in co-endemic settings with multiple circulating parasite species. Enzyme-linked immunosorbent assay (ELISA) has been the alternative technique to evaluate the infectivity of mosquitoes especially in field studies however it is semi-quantitative. Molecular techniques that have been used to detect the mosquito stages of malaria parasites includingP. vivax. Here, we present a quantitative real-time assay (qPCR) assay that can be used to detect low-densityP. vivaxoocyst and sporozoite infections. Parasite detection via qPCR after performing the conventional DNA extraction versus direct qPCR following heating of the infected mosquito samples was compared.

Methods

Colony rearedAnopheles farautimosquitoes were exposed to blood samples collected from infected individuals using a direct membrane feeding assay. The fully fed mosquitoes were kept for 7 and 14 days post-feed before dissection to confirm presence of oocysts and sporozoites. Infected mosquito guts and the salivary glands (with the head and thorax) were stored and DNA was extracted either by heating or by performing conventional column-based DNA extraction. Following DNA extraction the infected samples were subjected to qPCR to detectP. vivaxparasites.

Results

DNA extraction of 1 or more oocysts by heating resulted in an overall sensitivity of 78% (57/73) and single oocysts infections were detected with a sensitivity of 82% (15/17) in the heating arm as well. We observed a 60% (18/30) sensitivity with sporozoites where DNA was extracted using the conventional DNA extraction method prior to qPCR diagnosis. We show that the heating method significantly improved the detection of oocysts over conventional DNA extraction. There was no significant difference in the DNA copy numbers when comparing the detection of oocysts from the conventional DNA extraction versus heating. There was also no significant difference in the detection rate of sporozoite samples when comparing the two DNA extraction protocols. However, we observed that the DNA copy numbers of the sporozoites detected in the heating arm was significantly higher than in the conventional DNA extraction arm.

Conclusion

We have adapted a qPCR assay which, when coupled with heating to release DNA reduces sample processing time and cost. Direct qPCR after heating will be a useful tool when investigating transmission blocking vaccines or antimalarials or when evaluating field caught mosquitoes for the presence of malaria parasites.
Magnitude of Needle Stick and Sharp Injuries and Associated Factors among Health Care Workers in Werabe Comprehensive Specialized Hospital, Southwest Ethiopia: A Cross-Sectional study
Authors: Halil Jemal , Berhanu Negalign , Dutamo Zeleke
Published: November 2022

Background

Needle-stick and sharp injuries were one of major leading risk factor for blood and body fluid born infections among health care workers (HCWs)

Objective

To assess the magnitude of occupational needle-stick and sharp injuries and associated factors among HCWs in Werabe Comprehensive Specialized Hospital (WCSH), Southwest Ethiopia

Methods

Facility based cross-sectional study was conducted at WCSH from 15 to 25 August, 2020. Stratified random sampling was used to select 213 HCWs in the Hospital. A self-administered questionnaire was employed to collect data. After proportional allocation to the professionals, simple random sampling was used for each stratum. Data was entered and analyzed by using Epi info version 7 and SPSS version 22, respectively. Odds ratio was used to assess the statistical association between outcome and independent variables in bivariate and multivariate logistic regression. Significance of statistical association was tested using 95% confidence interval (CI) and P-value (<0.05)

Result

28.40% of HCWs encountered needle-stick and sharp injuries in the last 1-year. HCWs who had job related stress, whose working hours was more than 8 hours per day and didn’t apply universal precaution were 8.6, 7.5 and 2.3 times more likely to encounter needle-stick and sharp injuries, respectively. HCWS with educational status above Diploma level were 90% less likely to face needle-stick and sharp injuries than their counterparts

Conclusion and recommendation

The prevalence of occupational needle- stick and sharp injury was high compared to earlier studies. Educational status of diploma and above, average working hour for more than eight hours per day, not-applying universal precautions and job related stresses were factors associated with occupational needle-stick and sharp injures. Refreshment training on universal precaution and minimizing the excess working hours per day among HCWs were crucial to decrease the risk of needle stick and sharp injuries
Validation and optimization of the Japanese version of the Adult Executive Functioning Inventory
Authors: Kawagoe Toshikazu , Kanekama Yori , Rupp Michael J.
Published: November 2022

Background

Executive function (EF) is an umbrella term used to describe higher-order cognitive processes. Among the test batteries for EF, the Adult Executive Functioning Inventory (ADEXI) is prominent because of several advantages: it is brief, focuses on the core concept of EF, and does not include hard-to-understand general expressions and/or things that are connected but not directly linked to EFs.

Aims

To translate the ADEXI into Japanese and reduce the number of items required for optimization. The validation was performed using external self-reporting and laboratory task measurements.

Methods

A Japanese version of the ADEXI (J-ADEXI) was created through a regular translation procedure and tested using confirmatory factor analysis (CFA). We also conducted a Mokken scaling analysis (MSA) to reduce the number of J-ADEXI items and correlational analyses with external surveys and laboratory tasks.

Results

Although both the original model with 14 items and new the reduced model with 12 items have adequate reliability and validity, the latter was better in terms of model fit. Through discussion, we determined that J-ADEXI includes all 14 items and allows the user to choose a scoring model (i.e., 12 or 14 items model).

Conclusions

The J-ADEXI could briefly assess EF with adequate psychometric properties, and this study may also provide clues towards the optimization of the original and/or other language versions of the ADEXI.
Childhood Cancer Survival in the Highly Vulnerable Population of South Texas: A Cohort Study
Authors: Wu Shenghui , Liu Yanning , Williams Melanie , Aguilar Christine , Ramirez Amelie G. , Mesa Ruben , Tomlinson Gail E.
Published: November 2022

Objective

This study examines childhood cancer survival rates and prognostic factors related to survival in the majority Hispanic population of South Texas.

Methods

The population-based cohort study used Texas Cancer Registry data (1995-2017) to examine survival and prognostic factors. Cox proportional hazard models and Kaplan-Meier survival curves were used for survival analyses.

Results

The 5-year relative survival rate for 7,999 South Texas cancer patients diagnosed at 0–19 years was 80.3% for all races/ethnicities. Hispanic patients had statistically significant lower 5-year relative survival rates than non-Hispanic White (NHW) patients for male and female together diagnosed at age≥5 years. When comparing survival among Hispanic and NHW patients for the most common cancer, acute lymphocytic leukemia (ALL), the difference was most significant in the 15-19 years age range, with 47.7% Hispanic patients surviving at 5 years compared to 78.4% of NHW counterparts. The multivariable-adjusted analysis showed that males had statistically significant 13% increased mortality risk than females [hazard ratio (HR): 1.13, 95% confidence interval (CI):1.01-1.26] for all cancer types. Comparing to patients diagnosed at ages 1–4 years, patients diagnosed at age < 1 year (HR: 1.69, 95% CI: 1.36-2.09), at 10-14 year (HR: 1.42, 95% CI: 1.20-1.68), or at 15–19 years (HR: 1.40, 95% CI: 1.20-1.64) had significant increased mortality risk. Comparing to NHW patients, Hispanic patients showed 38% significantly increased mortality risk for all cancer types, 66% for ALL, and 52% for brain cancer.

Conclusions

South Texas Hispanic patients had lower 5-year relative survival than NHW patients especially for ALL. Male gender, diagnosis at age<1 year or 10–19 years were also associated with decreased childhood cancer survival. Despite advances in treatment, Hispanic patients lag significantly behind NHW patients. Further cohort studies in South Texas are warranted to identify additional factors affecting survival and to develop interventional strategies.
Special Olympics global report on COVID-19 vaccination and reasons not to vaccinate among adults with intellectual disabilities
Authors: Lincoln Andrew E. , Dixon-Ibarra Alicia M. , Hanley John P. , Smith Ashlyn L. , Martin Kiki , Bazzano Alicia
Published: November 2022

Introduction

The COVID-19 pandemic has disproportionately affected people with intellectual disabilities worldwide. The objective of this study was to identify global rates of COVID-19 vaccination and reasons not to vaccinate among adults with intellectual disabilities (ID) associated with country economic income levels.

Methods

The Special Olympics COVID-19 online survey was administered in January-February 2022 to adults with ID from 138 countries. Descriptive analyses of survey responses include 95% margins of error. Logistic regression and Pearson Chi-squared tests were calculated to assess associations with predictive variables for vaccination using R 4.1.2 software.

Results

Participants (n=3560) represented 18 low (n=410), 35 lower-middle (n=1182), 41 upper-middle (n=837), and 44 high (n=1131) income countries. Globally, 76% (74.8-77.6%) received a COVID-19 vaccination while 49.5% (47.9-51.2%) received a COVID-19 booster. Upper-middle (93% (91.2-94.7%)) and high-income country (94% (92.1-95.0%)) participants had the highest rates of vaccination while low-income countries had the lowest rates (38% (33.3-42.7%)). In multivariate regression models, country economic income level (OR = 3.12, 95% CI [2.81, 3.48]), age (OR = 1.04, 95% CI [1.03, 1.05]), and living with family (OR = 0.70, 95% CI [0.53, 0.92]) were associated with vaccination. Among LLMICs, the major reason for not vaccinating was lack of access (41.2% (29.5-52.9%)). Globally, concerns about side effects (42%, (36.5-48.1%)) and parent/guardian not wanting the adult with ID to vaccinate (32% (26.1-37.0%)) were the most common reasons for not vaccinating.

Conclusion

Adults with ID from low and low-middle income countries reported fewer COVID-19 vaccinations, suggesting reduced access and availability of resources in these countries. Globally, COVID-19 vaccination levels among adults with ID were higher than the general population. Interventions should address the increased risk of infection for those in congregate living situations and family caregiver apprehension to vaccinate this high-risk population.
STRENGTH OF ASSOCIATION BETWEEN GENERALIZED/NONSPECIFIC COVID-19 SIGNS & SYMPTOMS WITH SARS-COV 2 SPECIFIC ORF, N, E GENES IDENTIFIED THROUGH REAL TIME PCR
Authors: Arif Muhammad , Abdullah Muhammad , Ahmed Sheikh , Larik Ehsan Ahmed , Baloch Ujala Naseer , Hussain Zakir , Iqbal Baig Mirza Zeeshan
Published: November 2022

BACKGROUND

Constant mutation in the SARS-COV2 virus genetic material is resulting in the appearance of new variants frequently hence the overall virulence, treatment resistance, replication modalities, transmissions rates and COVID-19 signs & symptoms are all changing regularly.

METHODOLOGY

From 1 January 2021 to 30 August 2022, the clinical lab at Fatima Jinnah General & Chest Hospital Quetta, Balochistan, determined a total of 3375 individuals to be COVID-19 positive because RT-PCR detected ORF, N, and E genes or their various Bi & Tri combinations in their samples. A questionnaire-based interview was conducted with each participant during sample collection. Body temperature more than 370c was recorded as Fever/Chill. Age, Comorbidities, A-symptomatic individuals & Vaccination status were all neglected during this study. Frequency tables were generated using MS-excel 2016, while Odds ratios were calculated using Chi-square test of association whereby 2×2 contingency tables between Mono, Bi & Tri combinations for ORF, N & E genes were cross associated with various generalized nonspecific COVID -19 signs and symptoms using Epi-info software. Absence of Genetic sequencing was the major limitation.

RESULTS

The study showed that individually the presence ofORF genewas found to be strongly associated“ Shortness of Breath/Difficulty in Breathing”, Diarrhea, Head ache & Vomitting. While the presence ofN- genewas found to be strongly associated withLoss of smell & taste, Head ache,Presistant Chest Pain & Bluish lips/Face. Where as the presence ofE-genewas found to be strongly associated withCough, Shortness of breath/ Difficulty in breathing, Sore throat, Diarrhea, Head ache & Laziness. In addition, the study also found that different Bi & Tri combinations of ORF, N & E genes in a COVID-19 positive patient expressed generalized non-specific COVID-19 signs & symptoms differently.

DISCUSSION & CONCLUSION

The presence of various SARS-COV2 genetic markers significantly alters the clinical presentation of COVID-19.
Subtypes of Relapsing-Remitting Multiple Sclerosis Identified by Network Analysis
Authors: Howlett-Prieto Quentin , Oommen Chelsea , Carrithers Michael D. , Wunsch Donald C. , Hier Daniel B.
Published: November 2022

The objective of this study was to use network analysis to identify subtypes of relapsing-remitting multiple sclerosis subjects based on their cumulative signs and symptoms. We reviewed the electronic medical records of 120 subjects with relapsing-remitting multiple sclerosis and recorded signs and symptoms. Signs and symptoms were mapped to a neuroontology and then collapsed into 16 superclasses by subsumption and normalized. Bipartite (subject-feature) and unipartite (subject-subject) network graphs were created using Gephi. Degree and weighted degree were calculated for each node. Graphs were partitioned into communities using the modularity score. Feature maps were used to visualize differences in features by the community. Network analysis of the unipartite graph yielded a higher modularity score (0.49) than the bipartite graph (0.247). Network analysis can partition multiple sclerosis subjects into communities based on signs and symptoms. Communities of subjects with predominant motor, sensory, pain, fatigue, cognitive, behavior, and fatigue features were found. Larger datasets and additional partitioning algorithms are needed to confirm these results and elucidate their clinical significance.
Co-occurring Pathogenic Variants in 6q27 Associated with Dementia Spectrum Disorders in a Peruvian Family
Authors: Alvarez Karla Lucia F. , Aguilar-Pineda Jorge A. , Ortiz-Manrique Michelle M. , Paredes-Calderon Marluve F. , Cardenas-Quispe Bryan C. , Vera-Lopez Karin J. , Goyzueta-Mamani Luis D. , Chavez-Fumagalli Miguel A. , Del-Carpio Gonzalo Davila , Peralta-Mestas Antero , Musolino Patricia L. , Lino Cardenas Christian L.
Published: November 2022

Evidence suggests that there may be racial differences in risk factors associated with the development of Alzheimer’s disease and related dementias (ADRD). We used whole genome sequencing analysis and identified a novel combination of three pathogenic variants in the heterozygous state (UNC93A: rs7739897 andWDR27: rs61740334; rs3800544) in a Peruvian family with a strong clinical history of ADRD. Notably, the combination of these variants was present in two generations of affected individuals but absent in healthy members within the family.In silicoandin vitrostudies have provided insights into the pathogenicity of these variants. These studies predict the loss of function of the mutant UNC93A and WDR27 proteins which induced dramatic changes in the global transcriptomic signature of brain cells, including neurons, astrocytes, and especially pericytes and vascular smooth muscle cells, and thus indicating that the combination of these three variants may affect the neurovascular unit. In addition, key known molecular pathways associated with ADRD were enriched in brain cells with low levels of UNC93A and WDR27. Our findings have thus identified a genetic risk factor for familial ADRD in a Peruvian family with an Amerindian ancestral background.
Subjective and Objective Assessment of Physical Activity in Older Adults: Results from Berlin Aging Study II
Authors: Vetter Valentin Max , Oezince Duygu Deniz , Kiselev Joern , Duezel Sandra , Demuth Ilja
Published: November 2022

Physical activity has a substantial impact on health and mortality. Besides questionnaires that rely on subjective assessment of activity levels, accelerometers can help to objectify an individual's physical activity. Physical activity was assessed with the GT3X activity monitor (ActiGraph LLC, USA) in 797 participants of the Berlin Aging Study II (BASE-II) and compared with questionnaire data obtained from the Rapid Assessment of Physical Activity (RAPA). Of all participants, 760 fulfilled the wear-time based inclusion criteria. Mean age was 75.6 years (SD: 3.8 years, range 66.0 - 94.1 years) and 53% of the included participants were female. Average wear time was 23.2 hours/day (SD 1.3 hours/day). Statistically significant differences between RAPA groups were found for all accelerometric variables except energy expenditure. Post-hoc analysis, however, suggested low agreement between subjective and objective assessment of physical activity. When focusing on the first question of the RAPA questionnaire, participants who reported to be "seldom or never active" showed statistically significant lower activity levels in Vector Magnitude, step counts, and cut-off defined moderate physical activity (p<0.05). Total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, fasting glucose and hemoglobin A1c were weakly correlated with accelerometric variables (Pearson's r <= 0.25). Results from this study suggest that subjectively assessed data from the RAPA and objectively assessed data from accelerometric variables obtained from the GT3X monitor are partially inconsistent in terms of the physical activity level of the participants.
Identifying Racial Disparities in Clozapine Prescriptions Among Schizophrenia Patients using Data from Electronic Health Records
Authors: Barry Spenser , Jarskog L Fredrik , Xia Kai , Torpunuri Rohit Simha , Wu Xiaoyu , Zeng Xiaoming
Published: November 2022

Objective

This study sought to assess the demographic factors that alter the likelihood of being prescribed clozapine. The primary hypothesis is that African American patients are less likely to be prescribed Clozapine than White and other racial groups. Additionally, this study aims to expand on earlier studies of clozapine by examining how multiple variables, especially social determinants of health, gender, rurality, and care patterns affect the rates at which clozapine is prescribed.

Methods

This observational study examines the racial disparities and other factors associated with receiving a clozapine prescription for patients with a schizophrenia diagnosis using structured data in the Electronic Health Records (EHR) from a multi-facility health system from 10/1/2015 - 11/30/2021. Bivariate analysis, multiple logistic regression, and sensitivity analysis tests were performed to determine which factors differed significantly between the group of patients who were prescribed clozapine and those who were not.

Results

Results showed that being white and having a higher socioeconomic income was associated with an increased clozapine prescription rate, while gender, rurality, age at first diagnosis, and ethnicity did not influence prescription likelihood. Increased treatment length was also associated with a greater likelihood of being prescribed clozapine.

Conclusion

African American patients are over-diagnosed with schizophrenia and under-prescribed clozapine compared to Caucasians after controlling for the variables associated with demographics, social determinants of health, and care access patterns. Future research is needed to understand and disentangle the biological, clinical, administrative, and societal causes behind the disparity in clozapine treatment.
Inflammatory ER Stress Responses Dictate the Immunopathogenic Progression of Systemic Candidiasis
Authors: Awasthi Deepika , Chopra Sahil , Cho Byuri A. , Emmanuelli Alexander , Sandoval Tito A. , Hwang Sung-Min , Chae Chang-Suk , Salvagno Camilla , Tan Chen , Vasquez-Urbina Liliana , Rodriguez Jose J. Fernandez , Santagostino Sara F. , Iwawaki Takao , Romero-Sandoval E. Alfonso , Crespo Mariano Sanchez , Morales Diana K. , Iliev Iliyan D. , Hohl Tobias M. , Cubillos-Ruiz Juan R.
Published: November 2022

Recognition of pathogen-associated molecular patterns can trigger the IRE1α arm of the endoplasmic reticulum (ER) stress response in immune cells. IRE1α activation has been shown to maintain ER homeostasis while simultaneously coordinating diverse immunomodulatory programs in the setting of bacterial and viral infections. However, the role of IRE1α signaling in innate immune responses to fungal pathogens is unknown. Here we report that systemic infection with the fungusCandida albicanscauses severe renal immunopathology by triggering inflammatory IRE1α hyperactivation in host myeloid cells. Mechanistically, sensing of fungal β-glucans by the C-type lectin receptor Dectin-1 induced Src–Syk–NOX-dependent accumulation of intracellular reactive oxygen species and the ensuing generation of lipid peroxidation byproducts that sustained IRE1α activation. Selective deletion of IRE1α in leukocytes, or treatment with an IRE1α pharmacological inhibitor, reduced detrimental inflammatory responses in the kidney and extended survival in mice systemically infected withC. albicans. Hence, controlling IRE1α overactivation may be useful to impede the fatal immunopathogenic progression of disseminated candidiasis.

One sentence summary

Innate IRE1α signaling in disseminated candidiasis
Hamsters are a model for post-COVID-19 alveolar regeneration mechanisms: an opportunity to understand post-acute sequelae of SARS-CoV-2
Authors: Heydemann Laura , Ciurkiewicz Małgorzata , Beythien Georg , Becker Kathrin , Schughart Klaus , Stanelle-Bertram Stephanie , Schaumburg Berfin , Mounogou-Kouassi Nancy , Beck Sebastian , Zickler Martin , Kühnel Mark , Gabriel Gülsah , Beineke Andreas , Baumgärtner Wolfgang , Armando Federico
Published: November 2022

A relevant number of coronavirus disease 2019 (COVID-19) survivors suffers from post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (PASC). Current evidence suggests a dysregulated alveolar regeneration in COVID-19 as a possible explanation for respiratory PASC symptoms, a phenomenon which deserves further investigation in a suitable animal model. This study investigates morphological, phenotypical and transcriptomic features of alveolar regeneration in SARS-CoV-2 infected Syrian golden hamsters. We demonstrate that CK8+alveolar differentiation intermediate (ADI) cells occur following SARS-CoV-2-induced diffuse alveolar damage. A subset of ADI cells shows nuclear accumulation of TP53 at 6- and 14-days post infection (dpi), indicating a prolonged arrest in the ADI state. Transcriptome data show the expression of gene signatures driving ADI cell senescence, epithelial-mesenchymal transition, and angiogenesis. Moreover, we show that multipotent CK14+airway basal cell progenitors migrate out of terminal bronchioles, aiding alveolar regeneration. At 14 dpi, presence of ADI cells, peribronchiolar proliferates, M2-type macrophages, and sub-pleural fibrosis is observed, indicating incomplete alveolar restoration. The results demonstrate that the hamster model reliably phenocopies indicators of a dysregulated alveolar regeneration of COVID-19 patients. The results provide important information on a translational COVID-19 model, which is crucial for its application in future research addressing pathomechanisms of PASC and in testing of prophylactic and therapeutic approaches for this syndrome.
The central role of pyruvate metabolism on the epigenetic and molecular maturation of bovine cumulus-oocytes complexes
Authors: da Silva João Vitor Alcantara , Ispada Jessica , da Fonseca Junior Aldcejam Martins , de Lima Camila Bruna , dos Santos Erika Cristina , Chiaratti Marcos Roberto , Nociti Ricardo Perecin , Milazzotto Marcella Pecora
Published: November 2022

Pyruvate, the end-product of glycolysis in aerobic conditions, is produced by cumulus cells, and is converted in Acetyl-CoA into the mitochondria of both cumulus cells (CCs) and oocytes as a master fuel input for the tricarboxylic acid cycle (TCA). The citrate generated in the TCA cycle can be directed to the cytoplasm and converted back to acetyl-CoA, being driven to lipid synthesis or, still, being used as the substrate for histones acetylation. This work aimed to verify the impact of pyruvate metabolism on the dynamic of lysine 9 histone 3 acetylation (H3K9ac) and RNA transcription in bovine cumulus-oocyte complexes during in vitro maturation (IVM). Bovine oocytes were IVM for 24h in three experimental groups: Control [IVM medium], sodium dichloroacetate [DCA, a stimulator of pyruvate oxidation in acetyl-CoA] or sodium iodoacetate [IA, a glycolysis inhibitor]. Our results show that both treatments change the metabolic profile of oocytes and CCs, stimulating the use of lipids for energy metabolism in the gamete. This leads to changes in the dynamics of H3K9ac during the IVM in both oocytes and CCs with impact on the synthesis of new transcripts in CCs. A total of 148 and 356 differentially expressed genes were identified in DCA and IA oocytes groups, respectively, when compared to the control group. In conclusion, disorders in pyruvate metabolism during maturation stimulate the beta-oxidation pathway, altering the mitochondrial metabolism, with consequences for the mRNA content of bovine oocytes.
Statistically unbiased prediction enables accurate denoising of voltage imaging data
Authors: Eom Minho , Han Seungjae , Kim Gyuri , Cho Eun-Seo , Sim Jueun , Park Pojeong , Lee Kang-Han , Kim Seonghoon , Rózsa Márton , Svoboda Karel , Choi Myunghwan , Kim Cheol-Hee , Cohen Adam E. , Chang Jae-Byum , Yoon Young-Gyu
Published: November 2022

Here we report SUPPORT (Statistically Unbiased Prediction utilizing sPatiOtempoRal information in imaging daTa), a self-supervised learning method for removing Poisson-Gaussian noise in voltage imaging data. SUPPORT is based on the insight that a pixel value in voltage imaging data is highly dependent on its spatially neighboring pixels in the same time frame, even when its temporally adjacent frames do not provide useful information for statistical prediction. Such spatiotemporal dependency is captured and utilized to accurately denoise voltage imaging data in which the existence of the action potential in a time frame cannot be inferred by the information in other frames. Through simulation and experiments, we show that SUPPORT enables precise denoising of voltage imaging data while preserving the underlying dynamics in the scene.