bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individual healthcare-seeking pathways for tuberculosis in Nigeria’s private sector during the COVID-19 pandemic
Authors: Oga-Omenka Charity , Rosapep Lauren , Huria Lavanya , Vasquez Nathaly Aguilera , Olusola-Faleye Bolanle , Kafi Mohammad Abdullah Heel , Sassi Angelina , Nwosu Chimdi , Johns Benjamin , Adamu Abdu , Chijioke-Akaniro Obioma , Anyaike Chukwuma , Pai Madhukar 
Published: June 2023

AbstractBackgroundPre-COVID-19, individuals with TB in Nigeria were often underdiagnosed and untreated. Care for TB was mostly in the public sector while only 15% of new cases in 2019 were from the private sector. Reports highlighted challenges in accessing care in the private sector, which accounted for 67% of all initial care-seeking. Our study examined patients’ health seeking pathways for TB in Nigeria’s private sector, and explored any changes to care pathways during COVID, based on patients’ perspectives.Design/MethodsWe conducted 180 cross-sectional surveys and 20 in-depth interviews with individuals having chest symptoms attending 18 high volume private clinics and hospitals in Kano and Lagos States. Questions focused on sociodemographic characteristics, health-seeking behavior and pathways to care during the COVID-19 periods. All surveys and interviews were conducted in May 2021.ResultsMost participants were male (n=111, 62%), with average age of 37. Half (n=96, 53.4%) sought healthcare within a week of symptoms, while few (n=20, 11.1%) waited over 2 months. TB positive individuals had more health-seeking delays, and TB negative had more provider delays. On average, participants visited 2 providers in Kano and 1.69 in Lagos, with 61 (75%) in Kano and 48 (59%) in Lagos visiting other providers before the recruitment facility. Private providers were the initial encounters for most participants (n=60 or 66.7% in Kano, n-83 or 92.3% in Lagos). Most respondents (164 or 91%) experienced short-lived pandemic-related restrictions, particularly during the lockdowns, affecting access to transportation, and closed facilities.ConclusionsThis study showed a few challenges in accessing TB healthcare in Nigeria, necessitating continued investment in healthcare infrastructure and resources, particularly in the private sector. Understanding the different care pathways and delays in care provides opportunities for targeted interventions to improve deployment of services closer to where patients first seek care.
A human pan-genomic analysis reconfigures the genetic and epigenetic make up of facioscapulohumeral muscular dystrophy
Authors: Salsi Valentina , Chiara Matteo , Pini Sara , Kuś Paweł , Ruggiero Lucia , Bonanno Silvia , Rodolico Carmelo , Previtali Stefano C. , D’Angelo Maria Grazia , Maggi Lorenzo , Lopergolo Diego , Kimmel Marek , Santorelli Filippo M. , Pesole Graziano , Tupler Rossella G. 
Published: June 2023

ABSTRACTFacioscapulohumeral muscular dystrophy (FSHD) is the only human disease associated with epigenetic changes at a macrosatellite array. Almost 95% of FSHD cases carry a reduced number (≤10) of tandem 3.3 kilobase repeats, termed D4Z4, on chromosome 4q35; remaining cases bear variants in chromatin remodeling factors, such as SMCHD1, DNMT3B, LRIF1. Reduced CpG methylation is used for the molecular diagnosis of FSHD, but D4Z4-like sequences dispersed in the genome can generate ambiguous results. By analyzing complete haplotype level assemblies from the T2T-CHM13 human genome and 86 haploid genomes from the human pangenome project, we uncovered the extensive number of D4Z4-like elements and their widespread inter- and intra-individual variability. An original analytical approach was developed to elucidate this previously unaccounted wealth of D4Z4-like elements and to analyze CpG methylation at D4Z4 in bisulfite-treated DNA from 29 FSHD index cases and 15 relatives. Integrated analysis of clinical phenotype, D4Z4 CpG methylation level and gene variants showed that low D4Z4 methylation was associated with variants in theSMCHD1gene, but not with the patients’ clinical phenotypes. This is the first study showing the relevance of the pangenome and T2T-CHM13 assemblies for investigating the genotype-phenotype correlation in genetic diseases. The extension and the variability of D4Z4-like elements scattered throughout the human genome and the inconsistent association of phenotypes with methylation profiles advocate for a critical revision of FSHD diagnostic tests based on D4Z4 CpG methylation assays and indicate that molecular investigations must be complemented by family studies for the proper interpretation of results.
Vagus nerve inflammation contributes to dysautonomia in COVID-19
Authors: Woo Marcel S. , Shafiq Mohsin , Fitzek Antonia , Dottermusch Matthias , Altmeppen Hermann , Mohammadi Behnam , Mayer Christina , Bal Lukas C. , Raich Lukas , Matschke Jakob , Krasemann Susanne , Pfefferle Susanne , Brehm Thomas Theo , Lütgehetmann Marc , Schädler Julia , Addo Marylin M. , Schulze Zur Wiesch Julian , Ondruschka Benjamin , Friese Manuel A. , Glatzel Markus 
Published: June 2023

ABSTRACTDysautonomia has substantially impacted acute COVID-19 severity as well as symptom burden after recovery from COVID-19 (long COVID), yet the underlying causes remain unknown. Here, we show that SARS-CoV-2 is detectable inpostmortemvagus nerve specimen together with inflammatory cell infiltration derived primarily from monocytes. This is associated with a decreased respiratory rate in non-survivors of critical COVID-19. Our data suggest that SARS-CoV-2 induces vagus nerve inflammation followed by autonomic dysfunction.
Test-retest reliability of a 2-dimensional and 3-dimensional visual assessment of body image disturbance in anorexia nervosa
Authors: Ralph-Nearman Christina , Arevian Armen C. , Karem Andrew , Llano-Rios Tomas F. , Sinik Megan , Moseman Scott , Feusner Jamie D. , Khalsa Sahib S. 
Published: June 2023

AbstractBody image disturbance (BID) is a diagnostic feature of anorexia nervosa (AN), with few reliable visual perceptual or attitudinal markers.Somatomapis a 2-dimensional (2D) and 3-dimensional (3D) digital assessment of BID, which has demonstrated utility. Test-retest reliability ofSomatomap2D and 3D digital assessment of BID in AN was examined. Fifty-nine inpatient participants with AN performed test-retest by a) outlining body concern areas on a 2D avatar for each independent area of concern; and b) sculpting 23 independent body parts on a randomized 3D avatar to reflect their perceived body size in length and girth. Participants corresponding body parts were physically measured to calculate discrepancy scores (i.e., 3D perceived minus measured values). Regional 2D BID test-retest differences were evaluated using z-scores to generate statistical visual body maps. Test-retest of 3D assessment reliability was evaluated by Intraclass Correlation Coefficient for individual and aggregated body parts. Somatomap 2D demonstrated excellent test-retest reliability with no statistical differences between test and retest z-scores. All 23 body parts on Somatomap 3D demonstrated statistically significant fair-to-excellent test-retest reliability in AN. Regions that are commonly of concern in AN, and combined measures, showed the highest reliability. Results suggest that Somatomap 2D and 3D may provide a reliable perceptual marker of visual BID in AN.
Understanding the cervical cancer self-collection preferences of women living in urban and rural Rwanda
Authors: Nair Varun , Dau Hallie , Vidler Marianne , AboMoslim Maryam , Mutamba Barbra , Scott McKerron , Nesbitt Zoey , Deodatha John , Byiringiro Schadrack Danson , Niyotwiringiye Charles , Mithani Nadia , Smith Laurie , Ogilvie Gina , Rulisa Stephen 
Published: June 2023

AbstractPURPOSECervical cancer is a leading cause of cancer among women in low- and middle-income countries. Women in Rwanda have high rates of cervical cancer due to limited access to effective screening methods. Research in other low-resource settings similar to Rwanda has shown that HPV-based self-collection is an effective cervical cancer screening method. This study aims to compare the preferences of Rwandan women in urban and rural settings toward self-collection and to report on factors related to self-collection amenability.METHODSA cross-sectional survey was conducted from June 1-9, 2022. Women were recruited from one urban and one rural clinic in Rwanda. Women were eligible for the study if they were ≥ 18 years and spoke Kinyarwanda or English. The survey consisted of 51 questions investigating demographics and attitudes towards self-collection for cervical cancer screening. We reported descriptive statistics stratified by urban and rural sites.RESULTSIn total, 169 urban and 205 rural women completed the survey. The majority of respondents at both sites had a primary school or lower education and were in a relationship. Both urban and rural respondents were open to self-collection; however, rates were higher in the rural site (79.9% urban and 95.6% rural; p-value<0.001). Similarly, women in rural areas were more likely to report feeling unembarrassed about self-collection (65.3% of urban, 76.8% of rural; p-value<0.001). Notably, almost all urban and rural respondents (97.6% urban and 98.5% rural) stated they would go for a cervical cancer pelvic examination to a nearby health center if their self-collected results indicated any concern (p-value=0.731).CONCLUSIONRwandan women in both urban and rural areas largely support self-collection for cervical cancer screening. Further research is needed to better understand how to implement self-collection screening services in Rwanda.
HPV Vaccination in immunosuppressed patients with established skin warts and non-melanoma skin cancer: A single-institutional cohort study
Authors: Bossart Simon , Daneluzzi Cloé , Moor Matthias B. , Hirzel Cédric , Seyed Jafari S. Morteza , Hunger Robert E. , Sidler Daniel 
Published: June 2023

AbstractBackgroundcSCC (cutaneous squameous cell carcinom) and its precursors are a major cause of morbidity especially in immunosuppressed patients and are frequently associated with human papilloma virus (HPV) infections.ObjectiveThe purpose of this study is to investigate the therapeutically potential of alpha-HPV vaccination for immunosuppressed patients with established cSCC and its precursors.MethodsIn this retrospective study, all patients who received Gardasil-9®, a nonavalent HPV vaccine, as secondary prophylaxis were examined. Dermatologic interventions in both the pre- and post-vaccination periods were analyzed with zero-inflated poisson regression and a proportional intensity model for repeated events with consideration of the clinically relevant cofactors.ResultsThe hazard ratio for major dermatologic interventions was 0.27 (CI 0.14-0.51, p <0.001) between pre- and post Gardasil-9® intervention. Gardasil-9® vaccination showed good efficacy in reducing major dermatologic interventions even after correction of relevant cofactors and national COVID-19 case loads during the observational period.LimitationThe retrospective study design and the rather low number of patients may influence study results. Furthermore, analysis of HPV types and data collection on vaccine-specific HPV antibody measurements was not possible.ConclusionAlpha-HPV vaccination may potentially cause a significant decrease in dermatologic interventions in immunosuppressed patients with high skin tumor burden.Capsule summaryLittle is known about a possible immunizing effect of alpha-vaccines in immunosuppressed patients with high skin tumor burdenAlpha-HPV vaccination such as Gardasil-9® may potentially cause a significant decrease in dermatologic interventions in IS patients with high skin tumor burden.
Topologic Parametric Response Mapping Identifies Tissue Subtypes Associated with Emphysema Progression
Authors: Wang Jennifer M. , Bell Alexander J. , Ram Sundaresh , Labaki Wassim W. , Hoff Benjamin A. , Murray Susan , Kazerooni Ella , Galban Stefanie , Hatt Charles R. , Han MeiLan K. , Galban Craig J. 
Published: June 2023

ABSTRACTRationale and ObjectivesSmall airways disease (SAD) and emphysema are significant components of COPD, a heterogenous disease where predicting progression is difficult. SAD, a principal cause of airflow obstruction in mild COPD, has been identified as a precursor to emphysema. Parametric Response Mapping (PRM) of chest computed tomography (CT) can help distinguish SAD from emphysema. Specifically, topologic PRM can define local patterns of both diseases to characterize how and in whom COPD progresses. We aimed to determine if distribution of CT-based PRM of functional SAD (fSAD) is associated with emphysema progression.Materials and MethodsWe analyzed paired inspiratory-expiratory chest CT scans at baseline and 5-year follow up in 1495 COPDGene subjects using topological analyses of PRM classifications. By spatially aligning temporal scans, we mapped local emphysema at year 5 to baseline lobar PRM-derived topological readouts. K-means clustering was applied to all observations. Subjects were subtyped based on predominant PRM cluster assignments and assessed using non-parametric statistical tests to determine differences in PRM values, pulmonary function metrics and clinical measures.ResultsWe identified distinct lobar imaging patterns and classified subjects into three radiologic subtypes: emphysema-dominant (ED), fSAD-dominant (FD), and fSAD-transition (FT: transition from healthy lung to fSAD). Relative to year 5 emphysema, FT showed rapid local emphysema progression (−57.5% ± 1.1) compared to FD (−49.9% ± 0.5) and ED (−33.1% ± 0.4). FT consisted primarily of at-risk subjects (roughly 60%) with normal spirometry.ConclusionThe FT subtype of COPD may allow earlier identification of individuals without spirometrically-defined COPD at-risk for developing emphysema.
U-shaped Association Between Mean Platelet Volume And Short-term Survival In Chinese Patients With Heart Failure
Authors: Huang Yuan-lei , Zhou Qi , Zheng Tao 
Published: June 2023

BackgroundMean Platelet Volume (MPV) has been proposed as a potential predictor of increased mortality risk at 6 months among Chinese patients with heart failure (HF). However, the current evidence supporting this association is limited.MethodsThis study aimed to investigate the relationship between MPV and HF short-term survival status. The data was obtained from a publicly accessible HF database in Zigong, Sichuan, and included information on 2008 Chinese patients. Baseline MPV was considered as the exposure while HF short-term survival status was the outcome. Two models, a binary logistic regression model and a two-piecewise linear model, were used to analyze the data.ResultsThe study revealed a U-shaped relationship between MPV and all-cause mortality in HF patients. When MPV levels were less than 9.8, every unit increase in MPV was associated with a 91% reduction (RR: 0.09; 95% CI: 0.03-0.24; P=0.0001) in the risk of death over the next six months. In contrast, at MPV levels above 9.8, each unit increase in MPV was linked to a 27% increase (RR: 1.27; 95% CI: 1.01-1.61; P=0.0434) in the probability of dying within the same period. Stratification by obesity status revealed no significant association between MPV and death in the obese population, while the same U-shaped association was observed among non-obese participants.ConclusionThe present study provides evidence of a U-shaped association between MPV and short-term survival in Chinese patients with heart failure. These findings suggest that MPV may serve as a potential prognostic marker for HF. However, further studies are needed to validate these results and to explore the underlying mechanisms of this association. The observed U-shaped association did not apply to obese patients, suggesting that the effect of MPV on mortality risk in HF patients may be influenced by body weight.
Crykey: Rapid Identification of SARS-CoV-2 Cryptic Mutations in Wastewater
Authors: Liu Yunxi , Sapoval Nicolae , Gallego-García Pilar , Tomás Laura , Posada David , Treangen Todd J. , Stadler Lauren B. 
Published: June 2023

AbstractWe present Crykey, a computational tool for rapidly identifying cryptic mutations of SARS-CoV-2. Specifically, we identify co-occurring single nucleotide mutations on the same sequencing read, called linked-read mutations, that are rare or entirely missing in existing databases, and have the potential to represent novel cryptic lineages found in wastewater. While previous approaches exist for identifying cryptic linked-read mutations from specific regions of the SARS-CoV-2 genome, there is a need for computational tools capable of efficiently tracking cryptic mutations across the entire genome and for tens of thousands of samples and with increased scrutiny, given their potential to represent either artifacts or hidden SARS-CoV-2 lineages. Crykey fills this gap by identifying rare linked-read mutations that pass stringent computational filters to limit the potential for artifacts. We evaluate the utility of Crykey on >3,000 wastewater and >22,000 clinical samples; our findings are three-fold: i) we identify hundreds of cryptic mutations that cover the entire SARS-CoV-2 genome, ii) we track the presence of these cryptic mutations across multiple wastewater treatment plants and over a three years of sampling in Houston, and iii) we find a handful of cryptic mutations in wastewater mirror cryptic mutations in clinical samples and investigate their potential to represent real cryptic lineages. In summary, Crykey enables large-scale detection of cryptic mutations representing potential cryptic lineages in wastewater.
Multiple beta cell-independent mechanisms drive hypoglycemia in Timothy syndrome
Authors: Matsui Maiko , Lynch Lauren E. , Distefano Isabella , Galante Allison , Gómez-Banoy Nicolas , Wang Hong-Gang , Gade Aravind R. , Sinden Daniel S. , Wei Eric Q. , Barnett Adam S. , Johnson Kenneth , Rubio-Navarro Alfonso , Li Ang K. , Marx Steven O. , McGraw Timothy E. , Thornton Paul , Timothy Katherine W. , Lo James C. , Pitt Geoffrey S. 
Published: June 2023

SummaryThe canonical G406R gain of function mutation that reduces inactivation and increases Ca2+influx through theCACNA1C-encoded CaV1.2 voltage gated Ca2+channel underlies the multisystem disorder Timothy syndrome (TS), characterized by invariant Long QT syndrome and consequent life-threatening arrhythmias. Severe episodic hypoglycemia, which exacerbates arrhythmia risk, is among the myriad non-cardiac TS pathologies that are poorly characterized. While hypoglycemia is thought to result from increased Ca2+influx through CaV1.2 channels in pancreatic beta cells and consequent hyperinsulinism, this mechanism has never been demonstrated due to a lack of informative animal models, thus hampering development of preventive strategies. We generated a CaV1.2 G406R knockin mouse model that recapitulates key TS features including hypoglycemia. Unexpectedly, these mice did not show hyperactive beta cells or hyperinsulinism in the setting of normal intrinsic beta cell function, suggesting dysregulated glucose homeostasis. We discovered multiple alternative contributors to hypoglycemia, including perturbed counterregulatory hormone responses with defects in glucagon secretion and abnormal hypothalamic glucose sensing. Together, these data provide new insights into physiological contributions of the broadly expressed CaV1.2 channel and reveal integrated consequences of the mutant channel that underlie the life-threatening events in TS.Brief SummaryGain of function mutant CaV1.2 channels drive hypoglycemia through adverse effects on counterregulatory hormones and central nervous system glucose sensing
Sex-Specific Clinical and Genetic Factors Associated with Adverse Outcomes in Hypertrophic Cardiomyopathy
Authors: Butters Alexandra , Arnott Clare , Sweeting Joanna , Claggett Brian , Cuomo Anna , Abrams Dominic , Ashley Euan A. , Day Sharlene M. , Helms Adam S. , Lampert Rachel , Lin Kim , Michels Michelle , Miller Erin M. , Olivotto Iacopo , Owens Anjali , Parikh Victoria N. , Pereira Alexandre C. , Rossano Joseph W. , Ryan Thomas D. , Saberi Sara , Stendahl John C. , Ware James S. , Atherton John , Semsarian Christopher , Lakdawala Neal K. , Ho Carolyn Y. , Ingles Jodie 
Published: June 2023

ABSTRACTBackgroundWomen with HCM present at a more advanced stage of the disease and have a higher risk of heart failure and death. The factors contributing to these differences are unclear. We aimed to investigate sex differences in clinical and genetic factors associated with adverse outcomes in the Sarcomeric Human Cardiomyopathy Registry (SHaRe).MethodsCox proportional hazard models were fit with a sex interaction term to determine if significant sex differences existed in the association between risk factors and outcomes. Models were fit separately for women and men to find the sex-specific hazard ratio.ResultsAfter a mean follow-up of 6.4 years, women had a higher risk of heart failure (HR 1.51; 95% CI 1.21-1.88, p=0.0003) but a lower risk of atrial fibrillation (0.74; 0.59-0.93; p<0.0001) and ventricular arrhythmia (0.60; 0.38-0.94; p=0.027) than men. No sex difference was observed for death (p=0.84). Sarcomere-positive men had a higher risk of heart failure and death, not seen in women (p-heterogeneity=0.006 & p-heterogeneity=0.035, respectively).MYBPC3variants were associated with lower heart failure risk in women than other HCM subgroups, with no significant change for men (p-heterogeneity <0.0001). Women with moderate risk of ventricular arrhythmia (4% to <6% ESC risk score) were at a higher risk of ventricular arrhythmia than those scoring <4%, not observed in men (p-heterogeneity= 0.019).ConclusionClinical and genetic factors contributing to adverse outcomes in HCM affect women and men differently. Research to inform sex-specific management of HCM could improve outcomes for both sexes.
Hypertension Among Adults With HIV Initiating Antiretroviral Therapy in Freetown, Sierra Leone: A Cross-sectional Study
Authors: Yendewa George A. , Jiba Darlinda F. , Sesay Daniel , Namanga Enanga Sonia , Yendewa Sahr A. , Barrie Umu , Deen Gibrilla F. , Sahr Foday , Salata Robert A. , Russel James B.W. , Lakoh Sulaiman 
Published: June 2023

ABSTRACTBackgroundHypertension is a major contributor to cardiovascular morbidity and mortality in people with HIV (PWH). However, screening and identification among PWH initiating antiretroviral therapy (ART) in sub-Saharan Africa is understudied.We aimed to assess the prevalence of hypertension and its associated factors among newly diagnosed PWH in Freetown, Sierra Leone.MethodsWe used a cross-sectional study design to assess the baseline characteristics of newly diagnosed ART-naïve PWH at Connaught Hospital in Freetown from March 2021 to March 2022. We categorized patients as having normal blood pressure (<120/80mmHg), pre-hypertension (systolic 120-139 mmHg or diastolic 80-89 mmHg), and hypertension (systolic ≥140 mmHg or diastolic ≥90 mmHg). We used logistic regression models to identify factors independently associated with hypertension.Results918 PWH were studied (55.0% female, median age 33 years). The prevalence of hypertension was 20.0% and 29.5% were pre-hypertensive. In univariate analysis, hypertension prevalence increased with age, body mass index (BMI), smoking, alcohol consumption, and being Christian (all p < 0.05). In multivariate logistic regression analysis, ages 40-49 years (aOR 2.15, 95% CI 1.30-3.57), 50-59 years (aOR 2.30, 95% CI 1.26-4.18), ≥ 60 years (aOR 3.08, 95% CI 1.28-7.41), BMI ≥ 30 kg/m2(aOR 2.34, 95% CI 1.11-4.93), identifying as a Christian (aOR 1.45, 95% CI 1.01-2.11), and smoking (aOR 1.67, 95% CI 1.04-2.69) were significantly associated with hypertension.ConclusionsWe observed a significant burden of hypertension among ART-naïve PWH in Sierra Leone, emphasizing the importance of early identification and management to help reduce cardiovascular morbidity and mortality.