bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seroprevalence of anti-ganglionic acetylcholine receptor antibodies in patients with functional neurological symptom disorder/conversion disorder
Authors: Nagata Ryusei , Matsuura Eiji , Nozuma Satoshi , Dozono Mika , Noguchi Yutaka , Ando Masahiro , Hiramatsu Yu , Kodama Daisuke , Tanaka Masakazu , Kubota Ryuji , Yamakuchi Munekazu , Higuchi Yujiro , Sakiyama Yusuke , Arata Hitoshi , Higashi Keiko , Hashiguchi Teruto , Nakane Shunya , Takashima Hiroshi 
Published: October 2022

AbstractBackgroundAutoimmune autonomic ganglionopathy (AAG) is a rare disorder characterized by autonomic failure associated with the presence of anti-ganglionic acetylcholine receptor (gAChR) antibodies; however, several studies have reported that individuals with anti-gAChR antibodies present with central nervous system (CNS) symptoms such as impaired consciousness and seizures. In the present study, we investigated whether the presence of serum anti-gAChR antibodies correlated with autonomic symptoms in patients with functional neurological symptom disorder/conversion disorder (FNSD/CD).MethodsClinical data were collected for 59 patients presenting with neurologically unexplained motor and sensory symptoms at the Department of Neurology and Geriatrics between January 2013 and October 2017 and who were ultimately diagnosed with FNSD/CD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Correlations between serum anti-gAChR antibodies and clinical symptoms and laboratory data were analyzed. Data analysis was conducted in 2021.ResultsOf the 59 patients with FNSD/CD, 52 (88.1%) exhibited autonomic disturbances and 16 (27.1%) were positive for serum anti-gAChR antibodies. Cardiovascular autonomic dysfunction, including orthostatic hypotension, was significantly more prevalent (75.0%vs34.9%,p= 0.008), whereas involuntary movements were significantly less prevalent (31.3%vs69.8%,p= 0.007), among anti-gAChR antibody-positive compared with - negative patients. Anti-gAChR antibody serostatus did not correlate significantly with the frequency of other autonomic, sensory, or motor symptoms analyzed.ConclusionsAn autoimmune mechanism mediated by anti-gAChR antibodies may be involved in the etiology of FNSD/CD in a subgroup of patients.
The Association of Alpha Globin Gene Copy Number with Exhaled Nitric Oxide in a Cross-sectional Study of Healthy Black Adults
Authors: Ruhl A. Parker , Jackson Jarrett M. , Carhuas Carlos J. , Niño de Rivera Jessica G. , Fay Michael P. , Weinberg J. Brice , Que Loretta G. , Ackerman Hans C. 
Published: October 2022

ABSTRACTIntroductionThe genetic determinants of fractional exhalation of nitric oxide (FeNO), a marker of lung inflammation, are understudied in Black individuals. Alpha globin (HBA) restricts nitric oxide signaling in arterial endothelial cells via interactions with nitric oxide synthase (NOS); however, its role in regulating the release of NO from respiratory epithelium is less well understood. We hypothesized that anHBAgene deletion, common among Black individuals, would be associated with higher FeNO.MethodsHealthy Black adults were enrolled at four study sites in North Carolina from 2005-2008. FeNO was measured in triplicate using a nitric oxide analyzer. The −3.7 kbHBAgene deletion was genotyped using droplet digital PCR on genomic DNA. The association of FeNO withHBAcopy number was evaluated using multivariable linear regression employing a linear effect ofHBAcopy number and adjusting for age, sex, and serum IgE levels. Post-hoc analysis employing a recessive mode of inheritance was performed.Results895 individuals were in enrolled in the study and 720 consented for future genetic research; 643 had complete data and were included in this analysis. Median (25th, 75th) FeNO was 20 (13, 31) ppb.HBAgenotypes were: 30 (4.7%) -a/-a, 197 (30.6%) -a/aa, 405 (63%) aa/aa, and 8 (1.2%) aa/aaa. Subjects were 35% male with median age 20 (19, 22) years. Multivariable linear regression analysis revealed no association between FeNO andHBAcopy number (β = −0.005 [95% CI: −0.042, 0.033], p=0.81). In the post-hoc sensitivity analysis, homozygosity for the HBA gene deletion was associated with higher FeNO (β = 0.107 [95% CI 0.003, 0.212]; p = 0.045)ConclusionWe found no association betweenHBAcopy number and FeNO using a prespecified additive genetic model. However, a post hoc recessive genetic model found FeNO to be higher among subjects homozygous for theHBAdeletion.KEY MESSAGESWhat is already known on this topic– The alpha subunit of hemoglobin restricts the release of nitric oxide from vascular endothelial cells, but alpha globin’s role in restricting exhaled nitric oxide is less well understood.What this study adds– We examined the association between fractional exhaled nitric oxide and deletion of the alpha globin gene, a frequent genetic polymorphism among people with African or Asian ancestry. We found that healthy Black individuals who were homozygous for the alpha globin gene deletion had higher fractional exhaled nitric oxide, consistent with alpha globin’s role as a nitric oxide restrictor.How this study might affect research, practice or policy– An alpha globin gene deletion, commonly found among Black individuals, may increase fractional exhaled nitric oxide. Whether this changes the normal range of fractional exhaled nitric oxide for Black individuals or impacts the risk of developing asthma requires further study.
Time trends of mental health indicators in Germany’s adult population before and during the COVID-19 pandemic
Authors: Mauz Elvira , Walther Lena , Junker Stephan , Kersjes Christina , Damerow Stefan , Eicher Sophie , Hölling Heike , Müters Stephan , Peitz Diana , Schnitzer Susanne , Thom Julia 
Published: October 2022

BackgroundTimes of crisis such as the COVID-19 pandemic are expected to compromise mental health. Despite a large number of studies, evidence on the development of mental health in general populations during the pandemic is inconclusive. One reason may be that representative data spanning the whole pandemic and allowing for comparisons to pre-pandemic data are scarce.MethodsWe analyzed representative data from telephone surveys of Germany’s adults: “German Health Update (GEDA)” and “COVID-19 vaccination rate monitoring in Germany (COVIMO)”. Three indicators of mental health were observed in approximately 1,000 and later 3,000 randomly sampled participants monthly until June 2022: symptoms of depression (observed since April 2019 using the PHQ-2), symptoms of anxiety (observed since March 2021 using the GAD-2) and self-rated mental health (observed since March 2021 using a single item). We produced time series graphs including estimated three-month moving means and proportions of individuals with a positive screen (PHQ/GAD-2 score ≥ 3) and of those reporting very good/excellent mental health, as well as smoothing curves. We also compared time periods between years. Analyses were stratified by sex, age, and level of education.ResultsWhile mean depressive symptom scores declined from the first wave of the pandemic to summer 2020, they increased from October 2020 and remained consistently elevated throughout 2021 with another increase between 2021 and 2022. Correspondingly, the proportion of positive screens first decreased from 11.1 % in spring/summer 2019 to 9.3 % in the same period in 2020 and then rose to 13.1 % in 2021 and to 16.9 % in 2022. While depressive symptoms increased in all subgroups at different times, developments among women, the youngest and eldest adults, and the high level of education group stand out. Furthermore, symptoms of anxiety increased while self-rated mental health decreased between 2021 and 2022.ConclusionsElevated symptom levels and reduced self-rated mental health at the end of our observation period in June 2022 call for further continuous mental health surveillance. Mental healthcare needs of the population should be monitored closely. Findings should serve to inform policymakers and clinicians of ongoing dynamics to guide health promotion, prevention, and care.
Brief report: Reclassifying SCLC-Y as SMARCA4 deficient malignancies - resolving the controversy
Authors: Ng Jin , Cai Ling , Girard Luc , Prall Owen W.J. , Rajan Neeha , Khoo Christine , Batrouney Ahida , Kersbergen Ariena , Christie Michael , Minna John D. , Burr Marian L. , Sutherland Kate D. 
Published: October 2022

ABSTRACTIntroductionThe classification of small cell lung cancer (SCLC) into distinct molecular subtypes defined by ASCL1, NEUROD1, POU2F3 or YAP1 expression, paves the way for the development of targeted therapeutics. However, the existence of a distinct YAP1-expressing SCLC subtype remains controversial. Here we have undertaken a detailed molecular and histological characterisation of YAP1 expressing SCLC-Y to understand the biology of this proposed subtype.MethodsThe mutational landscape of human SCLC cell lines was interrogated to identify pathogenic genomic alterations unique to SCLC-Y. Xenograft tumours generated from cell lines representing the molecular subtypes of SCLC (SCLC-A, -N, -P and -Y) were evaluated by a panel of pathologists. Diagnoses were validated by transcriptomic analysis of primary tumour and human cell line datasets.ResultsUnexpectedly, pathogenic mutations in SMARCA4 were identified in six of eight SCLC-Y cell lines and correlated with reduced SMARCA4 mRNA and protein expression. Pathologist evaluations revealed that SMARCA4-deficient SCLC-Y tumours exhibited features consistent with thoracic SMARCA4-deficient undifferentiated tumours (SMARCA4-UT). Similarly, the transcriptional profile SMARCA4-mutant SCLC-Y lines more closely resembled primary SMARCA4-UT, or SMARCA4-deficient non-small cell carcinoma, than SCLC. Combining clinical, pathological, transcriptomic, and genetic data we found little evidence to support a diagnosis of SCLC for any of the YAP1-expressing cell lines originally used to define the SCLC-Y subtype.ConclusionsSCLC-Y cell lines harbour inactivatingSMARCA4mutations and exhibit characteristics consistent with SMARCA4-deficient malignancies rather than SCLC. Our findings suggest that, unlike ASCL1, NEUROD1 and POU2F3, YAP1 is not a subtype defining transcription factor in SCLC.
Knowledge, attitude and practice of primary school teachers toward epilepsy in Khartoum city, Sudan: A cross-sectional Study
Authors: MohamedSharif Abubaker A , Mohammed Isra Bdraldein Salih , Koko Abubaker E.A. 
Published: October 2022

AbstractObjectivesThe aim is to assess the knowledge, attitude and practice of the primary school teachers toward.MethodsA descriptive cross-sectional study was conducted among primary school teachers in Khartoum using self-administered, closed ended questionnaires.ResultsAlmost all teachers have heard about epilepsy before. Most of them believed that epilepsy was due to genetic factors (25.4%). (74.6%) of the participants thought that epilepsy was a contagious disease. Concerning practice, (26.5%) of the teachers who did first aid, they carried out all the steps of management truly.ConclusionTeachers generally have some knowledge about epilepsy, but there were also deficiencies in their management measures. Most of them heard about epilepsy from community reflecting the need for training sessions and a national program to raise their awareness and attitude.
Systematic Evaluation of Common Natural Language Processing Techniques to Codify Clinical Notes
Authors: Tavabi Nazgol , Singh Mallika , Pruneski James , Kiapour Ata M. 
Published: October 2022

AbstractProper codification of medical diagnoses and procedures is essential for optimized health care management, quality improvement, research, and reimbursement tasks within large healthcare systems. Assignment of diagnostic or procedure codes is a tedious manual process, often prone to human error. Natural Language Processing (NLP) have been suggested to facilitate these manual codification process. Yet, little is known on best practices to utilize NLP for such applications. Here we comprehensively assessed the performance of common NLP techniques to predict current procedural terminology (CPT) from operative notes. CPT codes are commonly used to track surgical procedures and interventions and are the primary means for reimbursement. The direct links between operative notes and CPT codes makes them a perfect vehicle to test the feasibility and performance of NLP for clinical codification. Our analysis of 100 most common musculoskeletal CPT codes suggest that traditional approaches (i.e., TF-IDF) can outperform resource intensive approaches like BERT, in addition to providing interpretability which can be very helpful and even crucial in the clinical domain. We also proposed a complexity measure to quantify the complexity of a classification task and how this measure could influence the effect of dataset size on model’s performance. Finally, we provide preliminary evidence that NLP can help minimize the codification error, including mislabeling due to human error.
Prevalence of diarrheagenicEscherichia coliand impact on child health in Cap-Haitien, Haiti
Authors: Diaz Jenna N. , Iannotti Lora L. , Louis Dulience Sherlie Jean , Vie Sydney , Jiang Xuntian , Grigura Vadim , Boncy Jacques , Marhône Pierre Francesca J. , Kuhlmann F. Matthew 
Published: October 2022

AbstractBackgroundDiarrheagenic Escherichiacoli(DEC) are common pathogens infecting children during their growth and development. Determining the epidemiology and the impact of DEC on child anthropometric measures informs prioritization of prevention efforts. These relationships were evaluated in a novel setting, Cap-Haitien, Haiti.MethodsA case-control study of children 6-36 months of age enrolled 99 cases with diarrhea and 96 asymptomatic controls. Assessments were performed at enrollment and one month follow-up. Established PCR methodologies targeted DEC using fecal swabs. The association between pathogens and anthropometric z-scores was determined using multiple linear regression.ResultsEnterotoxigenicEscherichia coli(ETEC) was identified in 21.9% of cases vs. 16.1% of controls with heat-stable producing ETEC significantly associated with symptomatic disease. EnteroaggregativeE. coli(EAEC) was found in 30.2% of cases vs. 27.3% of controls, and typical enteropathogenicE. coliin 6.3% vs. 4.0% of cases and controls, respectively. Multivariate linear regression demonstrated ETEC and EAEC were significantly associated with reduced weight-age z-score (WAZ) and height-age z-score (HAZ) after adjusting for confounders.ConclusionsDEC are prevalent in north Haitian children. ETEC, EAEC, household environment, and diet are associated with unfavorable anthropometric measures. Further studies may quantify the contribution of individual pathogens to adverse health outcomes.Author SummaryMultiple factors contribute to poor child growth and development including infectious diarrhea, malnutrition, and water, sanitation, and hygiene infrastructure. Efforts to improve child development require prioritization based on their cost and expected benefits. This study contributes to prioritization efforts by determining the local burden of disease in an understudied region, Cap-Haitien, Haiti, and associating this burden with measures of child growth. Moreover, it captures data on social determinants contributing to child growth to control for confounding variables. Unlike prior studies in Haiti, we evaluated children with diarrheal disease in the community instead of the hospital setting. Ultimately, we showed that EnterotoxigenicEscherichia coliand EnteroaggregativeE. coliare common and associated with surrogate measures of poor child growth. This result suggests that ETEC vaccination efforts may have a strong effect on improving child health. This work supports the continued investments in the development of ETEC vaccines.
Infection-induced immunity is associated with protection against SARS-CoV-2 infection, but not decreased infectivity during household transmission
Authors: Frutos Aaron M , Kuan Guillermina , Lopez Roger , Ojeda Sergio , Shotwell Abigail , Sanchez Nery , Saborio Saira , Plazaola Miguel , Barilla Carlos , Kenah Eben , Balmaseda Angel , Gordon Aubree 
Published: October 2022

BackgroundUnderstanding the impact of infection-induced immunity on SARS-CoV-2 transmission will provide insight into the transition of SARS-CoV-2 to endemicity. Here we estimate the effects of prior infection induced immunity and children on SARS-CoV-2 transmission in households.MethodsWe conducted a household cohort study between March 2020-June 2022 in Managua, Nicaragua where when one household member tests positive for SARS-CoV-2, household members are closely monitored for SARS-CoV-2 infection. Using a pairwise survival model, we estimate the association of infection period, age, symptoms, and infection-induced immunity with secondary attack risk.ResultsOverall transmission occurred in 72.4% of households, 42% of household contacts were infected and the secondary attack risk was 13.0% (95% CI: 11.7, 14.6). Prior immunity did not impact the probability of transmitting SARS-CoV-2. However, participants with pre-existing infection-induced immunity were half as likely to be infected compared to naïve individuals (RR 0.53, 95% CI: 0.39, 0.72), but this reduction was not observed in children. Likewise, symptomatic infected individuals were more likely to transmit (RR 24.4, 95% CI: 7.8, 76.1); however, symptom presentation was not associated with infectivity of young children. Young children were less likely to transmit SARS-CoV-2 than adults. During the omicron era, infection-induced immunity remained protective against infection.ConclusionsInfection-induced immunity is associated with protection against infection for adults and adolescents. While young children are less infectious, prior infection and asymptomatic presentation did not reduce their infectivity as was seen in adults. As SARS-CoV-2 transitions to endemicity, children may become more important in transmission dynamics.Article summaryInfection-induced immunity protects against SARS-CoV-2 infection for adolescents and adults; however, there was no protection in children. Prior immunity in an infected individual did not impact the probability they will spread SARS-CoV-2 in a household setting.
Prediction of the risk for diabetic neuropathy among diabetes mellitus patients at selected referral hospitals, in Amhara regional state Northwest Ethiopia, January, 2005- December 2021; Development and validation of risk prediction model
Authors: Gelaw Negalgn Byadgie , Muche Achenef Asmamaw , Alem Adugnaw Zeleke , Gebi Nebiyu Bekele , Chekol Yazachew Moges , Tesfie Tigabu Kidie , Tebeje Tsion Mulat 
Published: October 2022

AbstractBackgroundDiabetic neuropathy is the most common complication in both Type-1 and Type-2 DM patients with more than one half of all patients developing nerve dysfunction in their lifetime. Although, risk prediction model was developed for diabetic neuropathy in developed countries, It is not applicable in clinical practice, due to poor data, methodological problems, inappropriately analyzed and reported. To date, no risk prediction model developed for diabetic neuropathy among DM in Ethiopia, Therefore, this study aimed prediction the risk of diabetic neuropathy among DM patients, used for guiding in clinical decision making for cliniciansObjectivePrediction of the risk for diabetic neuropathy among diabetes mellitus patients, in selected referral hospitals, Amhara regional state, northwest Ethiopia,2022MethodsA retrospective follow up study was conducted with a total of 808 DM patients were enrolled from January 1,2005 to December 30,2021 at two selected referral hospitals in Amhara regional state. Multi-stage sampling techniques were used and the data was collected by checklist from medical records by Kobo collect and exported to STATA version-17 for analysis. Lasso method were used to select predictors and entered to multivariable logistic regression with P-value<0.05 was used for nomogram development. Model performance was assessed by AUC and calibration plot. Internal validation was done through bootstrapping method and decision curve analysis was performed to evaluate net benefit of modelResultsThe incidence proportion of diabetic neuropathy among DM patients was 21.29 %(95% CI; 18.59, 24.25).In multivariable logistic regression glycemic control, other comorbidities, physical activity, hypertension, alcohol drinking, type of treatment, white blood cells and red blood cells count were statistically significant. Nomogram was developed, has discriminating power AUC; 73.2 %(95% CI; 69.0%, 77.3%) and calibration test (P-value = 0.45). It was internally validated by bootstrapping method with discrimination performance 71.7(95% CI; 67.2 %, 75.9%).It had less optimism coefficient (0.015).To make nomogram accessible, mobile based tool were developed. In machine learning, classification and regression tree has discriminating performance of 70.2 %(95 % CI; 65.8%, 74.6%).The model had high net benefit at different threshold probabilities in both nomogram and classification and regression tree.ConclusionThe developed nomogram and decision tree, has good level of accuracy and well calibration, easily individualized prediction of diabetic neuropathy. Both models had added net benefit in clinical practice and to be clinically applicable mobile based tool were developed.
kimma: flexible linear mixed effects modeling with kinship covariance for RNA-seq data
Authors: Dill-McFarland Kimberly A , Mitchell Kiana , Batchu Sashank , Segnitz R Max , Benson Basilin , Janczyk Tomasz , Cox Madison S , Mayanja-Kizza Harriet , Boom W Henry , Benchek Penelope , Stein Catherine M. , Hawn Thomas R , Altman Matthew C 
Published: October 2022

AbstractWe introduce kimma (Kinship In Mixed Model Analysis), an open-source R package for flexible linear mixed effects modeling of RNA-seq including covariates, weights, random effects, covariance matrices, and fit metrics. In simulated datasets, kimma detects differentially expressed genes (DEGs) with similar specificity, sensitivity, and computational time as limma unpaired and dream paired models. Unlike other software, kimma supports covariance matrices as well as fit metrics like AIC. Utilizing genetic kinship covariance, kimma revealed that kinship impacts model fit and DEG detection in a related cohort. Thus, kimma equals or outcompetes current DEG pipelines in sensitivity, computational time, and model complexity.
Initiator AUGs are discriminated from elongator AUGs predominantly through mRNA accessibility inC. crescentus
Authors: Ghosh Aishwarya , Bharmal Mohammed-Husain M. , Ghaleb Amar M. , Schrader Jared M. 
Published: October 2022

AbstractTranslation initiation in bacteria is thought to occur upon base-pairing between the Shine-Dalgarno site in the mRNA and anti-Shine-Dalgarno site in the rRNA. However, in many bacterial species, such asCaulobacter crescentus, a minority of mRNAs have Shine-Dalgarno sites. To examine the functional importance of Shine-Dalgarno sites inC. crescentus, we analyzed the transcriptome and found more Shine-Dalgarno sites exist in the coding sequence than preceding start codons. To examine the function of Shine-Dalgarno sites in initiation we designed a series of mutants with altered ribosome accessibility and Shine-Dalgarno content in translation initiation regions (TIRs) and elongator AUG regions (EARs). A lack of mRNA structure content is required for initiation in TIRs, and when introduced into EARs, can stimulate initiation, suggesting that low mRNA structure content is a major feature required for initiation. SD sites appear to stimulate initiation in TIRs, which generally lack structure content, but SD sites only stimulate initiation in EARs if RNA secondary structures are destabilized. Taken together, this suggests that the difference in secondary structure between TIRs and EARs directs ribosomes to start codons where SD base pairing can tune the efficiency of initiation, but SDs in EARs do not stimulate initiation as they are blocked by stable secondary structures. This highlights the importance of studying translation initiation mechanisms in diverse bacterial species.