bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal processing of tongue swab samples for Mycobacterium tuberculosis detection by the Xpert MTB/RIF Ultra assay
Authors: Chilambi Gayatri Shankar , Reiss Robert , Daivaa Naranjargal , Banada Padmapriya , De Vos Margaretha , Penn-Nicholson Adam , Alland David 
Published: June 2024

AbstractTongue swabs represent a potential alternative to sputum as a sample type for detecting pulmonary tuberculosis (TB) using molecular diagnostic tests. The methods used to process tongue swabs for testing in the WHO-recommended Xpert MTB/RIF Ultra (Xpert Ultra) assay vary greatly. We aimed to identify the optimal method for processing diagnostic tongue swabs for subsequent testing by Xpert Ultra. We compared four methods for treating dry tongue swabs with Xpert Ultra sample reagent (SR) mixed with various concentrations of Tris-EDTA-Tween (TET), to treatment with SR alone or to a commonly used SR-free heat-inactivation protocol. In each condition, swabs obtained from volunteers without TB were placed into test buffer spiked with known amounts ofMycobacterium tuberculosis(Mtb) strain H37Rv-mc26230. Swabs processed with 1:1 diluted SR buffer had the lowestMtblimit of detection (LOD) at 22.7 CFU/700 µl (95% CI 14.2-31.2), followed by 2:1 diluted SR buffer at 30.3 CFU/700 µl (95% CI 19.9-40.7), neat SR at 30.9 CFU/700 µl (95% CI 21.5-40.3) and SR prefilled in the Xpert Ultra at 57.1 CFU/700 µl (95% CI 42.4-71.7). Swabs processed using the heat-based protocol had the highest LOD (77.6 CFU/700 µl; 95% CI 51.2–104.0). Similar findings were observed for LOD of RIF-susceptibility. Assay sensitivity using the 2:1 diluted SR buffer did not vary considerably in the presence of sputum matrix or phosphate buffer saline. Further studies are needed to assess the performance of this processing protocol in a clinical setting.ImportanceXpert MTB/RIF Ultra (Xpert Ultra) is approved by the World Health Organization for the diagnosis of tuberculosis (TB). This test is typically performed using sputum specimens obtained from people with presumptive TB. In order to inactivateMtband aid liquefaction, sputum must be mixed with Xpert SR prior to transfer into the Xpert Ultra. However, some people under evaluation for TB are unable to produce sputum. Alternative sample types for TB diagnosis would therefore be of value. Oral-swabs, including tongue-swabs have shown promise, but there are technical challenges associated with sample processing. In this study, several new tongue swab processing conditions were evaluated, utilizing SR, either neat or diluted in buffer. The ability of Xpert Ultra to detect TB was improved under these conditions compared with the previously published heat-processing method (1–3), processing steps were simplified, and technical challenges were overcome.
Neural tube organoid generation: a robust and reproducible protocol from single mouse embryonic stem cells
Authors: Krammer Teresa , Tanaka Elly M. 
Published: June 2024

ABSTRACTThe development of mammals is a highly complex process, characterized by the necessity for precise concentration- and time-dependent signaling for correct pattern formation and morphogenesis. Despite considerable technological advancements and knowledge gathered, numerous aspects of mammalian development remain elusive. When examining the entire organism, it becomes challenging to disentangle the effects of individual pathways or the mechanism by which external stimuli guide the interference of surrounding tissues and factors. In addressing this complexity, three-dimensional (3D)in vitromodels such as organoids have emerged as valuable tools. Organoids, derived from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), exhibit tissue-like features that closely resemble theirin vivocounterparts in terms of expression patterns and functionality. Importantly, they offer accessibility for manipulation and extensive biological studies within a controlled experimental setting. Despite originating from pluripotent cultures, organoid systems often exhibit heterogeneity and substantial variability, limiting their utility when studying complex and intricate biological questions. Therefore, there is a pressing need for detailed protocols aimed at harmonizing procedures that result in high-quality reproducible data, reduction of materials used and which importantly permit the investigation of convoluted phenomena. In this context, we present an optimized protocol for the cultivation of neural tube organoids (NTOs)in vitro. By producing stable culture conditions and offering comprehensive troubleshooting strategies, this protocol enables the reliable and reproducible generation of NTOs which serve as an adequate model to study relevant scientific questions.SUMMARYThree-dimensional neural tube organoids (NTOs) derived from mouse embryonic stem cells are valuable tools to study the central nervous system during early development. Here, we present a step-by-step demonstration of an optimized protocol for cultivating NTOsin vitro, providing stable culture conditions and troubleshooting strategies for reliable and reproducible NTO generation.
Alzheimer’s disease-like features in resting state EEG/fMRI of cognitively intact and healthy middle-agedAPOE/PICALMrisk carriers
Authors: Dzianok Patrycja , Wojciechowski Jakub , Wolak Tomasz , Kublik Ewa 
Published: June 2024

AbstractIntroductionGenetic susceptibility is a primary factor contributing to etiology of late-onset Alzheimer’s disease (LOAD). The exact mechanisms and timeline through whichAPOE/PICALMinfluence brain functions and contribute to LOAD remain unidentified. This includes their effects on individuals prior to the development of the disease.MethodsAPOE/PICALMalleles were assessed to determine the genetic risk of LOAD in 79 healthy, middle-aged participants who underwent EEG and fMRI recordings. The resting-state signal was analyzed to estimate relative spectral power, complexity (Higuchi’s algorithm), and connectivity (coherence in EEG and ICA-based connectivity in fMRI).ResultsThe main findings indicated that individuals at risk for LOAD exhibited reduced signal complexity and the so-called “slowing of EEG” which are well-known EEG markers of AD. Additionally, these individuals showed altered functional connectivity in fMRI (within attention related areas).DiscussionRisk alleles ofAPOE/PICALMmay affect brain integrity and function prior to the onset of the disease
DeEPsnap: human essential gene prediction by integrating multi-omics data
Authors: Zhang Xue , Xiao Weijia , Cochran Brent , Xiao Wangxin 
Published: June 2024

AbstractEssential genes are necessary for the survival or reproduction of a living organism. The prediction and analysis of gene essentiality can advance our understanding of basic life and human diseases, and further boost the development of new drugs. Wet lab methods for identifying cell essential genes are often costly, time-consuming, and laborious. As a complement, computational methods have been proposed to predict essential genes by integrating multiple biological data sources. Most of these methods are evaluated on model organisms. However, prediction methods for human essential genes are still limited and the relationship between human gene essentiality and different biological information still needs to be explored. In addition, exploring suitable deep learning techniques to overcome the limitations of traditional machine learning methods and improve prediction accuracy is also important and interesting. We propose a snapshot ensemble deep neural network method, DeEPsnap, to predict human essential genes. DeEPsnap integrates sequence features derived from DNA and protein sequence data with features extracted or learned from multiple types of functional data, such as gene ontology, protein complex, protein domain, and protein-protein interaction network. More than 200 features from these biological data are extracted/learned which are integrated together to train a series of cost-sensitive deep neural networks by utilizing multiple deep learning techniques. The proposed snapshot mechanism enables us to train multiple models without increasing extra training effort and cost. The experimental results of 10-fold cross-validation show that DeEPsnap can accurately predict human gene essentiality with an average AUROC (Area Under the Receiver Operating Characteristic curve) of 96.1%, the average AUPRC (Area under the Precision-Recall curve) of 93.82%, the average accuracy of 92.21%, and the average F1 measure about 80.62%. In addition, the comparison of experimental results shows that DeEPsnap outperforms several popular traditional machine learning models and deep learning models. We have demonstrated that the proposed method, DeEPsnap, is effective for predicting human essential genes.
EngineeringRhodosporidium toruloidesfor sustainable production of value-added punicic acid from glucose and wood residues
Authors: Wang Juli , Haddis Dagem Zekaryas , Xiao Qiong , Bressler David C , Chen Guanqun 
Published: June 2024

AbstractRhodosporidium toruloideshas emerged as a prominent candidate for producing single-cell oil from cost-effective feedstocks. In this study, the capability ofR. toruloidesto produce punicic acid (PuA), a representative plant unusual fatty acid, was investigated. The introduction of acyl lipid desaturase and conjugase (PgFADX) allowedR. toruloidesto accumulate 3.7% of total fatty acids as PuA. Delta-12 acyl lipid desaturase (PgFAD2) and diacylglycerol acyltransferase 2 were shown to benefit PuA production. The strain withPgFADXandPgFAD2coexpression accumulated 12% of its lipids as PuA from glucose, which translated into a PuA titer of 451.6 mg/L in shake flask condition. Utilizing wood hydrolysate as the feedstock, this strain produced 6.4% PuA with a titer of 310 mg/L. Taken together, the results demonstrated thatR. toruloidescould serve as an ideal platform for the production of plant-derived high-value conjugated fatty acid using agricultural and forestry waste as feedstock.
Using Photovoice to explore HIV self-testing and secondary distribution of HIV self-testing among gay, bisexual and other men who have sex with men in China
Authors: Wang Qianyun , Lu Ying , Ni Yuxin , Yan Xumeng , Jin Tan Rayner Kay , Wu Dan , Tucker Joseph D , Ong Jason J , Tang Weiming 
Published: June 2024

AbstractBackgroundHuman immunodeficiency virus self-testing (HIVST) has been globally recognized as a useful and reliable strategy to promote HIV testing, especially among marginalized populations. In order to improve the understanding of HIVST uptake of the test users, notably gay, bisexual and other men who have sex with men (GBMSM) in China, this study aims to qualitatively explore the HIVST uptake experiences among this population.MethodsThe study employed Photovoice methodology, theoretically built on documentary photography and critical consciousness, to explore the experiences of HIVST and secondary distribution among GBMSM in China. Participants created photos and citations and shared and discussed them in the group. Three focus groups and one follow-up interview were held virtually for each participant who were self-identified as gay or bisexual and used a self-test kit before.ResultsThis program recruited 22 participants from all throughout China. The findings revealed that systemic discrimination based on gay identification and AIDS-phobia both inside and outside the gay community, affected participants’ decision to take HIVST and to pass HIVST kits on to others. Participants utilized HIVST on a routine basis, citing sexual health concerns, psychological comfort, and a responsibility to their significant others as reasons for doing so.HIVST kitdistribution within intimacy,andthe significant role of gay-led community-based organizationswere found as characteristics of interactions between participants and those who they passed HIVST kit(s) on to. There were observed both facilitators and barriers to HIVST uptake and/or secondary distribution in this demographic.ConclusionIn the study, images and narratives were acquired through empowering GBMSM and promoting their community engagement to underline the necessity for measures and policies on promoting HIVST among this population. Findings also entailed the need to create a more inclusive society for sexual minorities and people living with HIV. Implications for promoting HIVST secondary distribution and limitations and strengths of the pioneer photovoice study among GBMSM in China were also listed.
Health status and care utilization among Afghan refugees newly resettled in Calgary, Canada between 2011-2020
Authors: Smati Hannah , Hassan Nour , Essar Mohammad Yasir , Abdaly Fawzia , Noori Shayesta , Grewal Rabina , Norrie Eric , Talavlikar Rachel , Bietz Julia , Kimball Sarah L. , Coakley Annalee , Chatterjee Avik , Fabreau Gabriel E. 
Published: June 2024

AbstractBackgroundThe United States and Canada have resettled over 120,000 Afghan refugees since August 2021, but sociodemographic and health status data remains sparse with investigations often limited to refugee entrance exams, standardized health screenings, or acute health settings.MethodsThis retrospective community-engaged cohort study investigated Afghan patients who received care between January 1, 2011 and December 31, 2020 at an interdisciplinary specialized refugee clinic in Calgary, Canada that provides care to newly arrived refugees. Two reviewers independently extracted and manually verified sociodemographic factors, medical diagnoses, and clinic utilization variables from patients’ electronic medical records, then coded patient diagnoses into ICD-10 codes and chapter groups. Diagnosis frequencies were calculated and stratified by age group and sex. We corroborated these findings with Afghan refugee co-investigators.FindingsAmong 402 Afghan refugee patients, 228 were adults (mean age 34·2 [SD 13] years), and 174 were children (mean age 7·5 [SD 5·4] years). We identified 1535 total individual diagnoses and classified them into 382 unique ICD-10 codes. Patients had a median 2 diagnoses each [IQR 0-6], 4 clinic visits across primary, specialty and multidisciplinary care annually, and an 11% appointment no-show rate. Among adults, the most frequent diagnoses were abdominal pain (26·3%, 60/228), mechanical back pain (20·2%, 46/228), and H. pylori infection (19·3%, 44/228). Among children, the most frequent diagnoses were upper respiratory tract infection (12·1%, 21/174),Giardia(10·3%, 18/174), and short stature (7·5%, 13/174).InterpretationRecently resettled Afghan refugees in Canada were relatively young, experienced diverse health characteristics, and had multi-specialty care engagement in their first two years after arrival. These findings may guide specialized healthcare provision to this inadequately characterized but growing population of refugee arrivals in North America and elsewhere.FundingResearch grants from the M.S.I. Foundation and University of Calgary O’Brien Institute for Public Health
Subthreshold intracortical microstimulation of human somatosensory cortex enhances tactile sensitivity
Authors: Osborn Luke E. , Christie Breanne , McMullen David P. , Arriola Victoria , Thomas Tessy M. , Pawar Ambarish S. , Nickl Robert W. , Anaya Manuel A. , Wester Brock A. , Greenspon Charles M. , Cantarero Gabriela L. , Celnik Pablo A. , Bensmaia Sliman J. , Yau Jeffrey M. , Fifer Matthew S. , Tenore Francesco V. 
Published: June 2024

ABSTRACTIntracortical microstimulation (ICMS) of the somatosensory cortex activates neurons around the stimulating electrodes and can elicit tactile sensations. However, it is not clear how the direct activation of cortical neurons influences their ability to process additional tactile inputs originating from the skin. In a human implanted with chronic microelectrode arrays in both left and right somatosensory cortices, we presented mechanical vibration to the skin while simultaneously delivering ICMS and quantified the effects of combined mechanical and electrical stimulation on tactile perception. We found that subthreshold ICMS enhanced sensitivity to touch on the skin, as evidenced by a reduction in vibrotactile detection thresholds (median: −1.5 dB), but subthreshold vibration did not systematically impact the detectability of ICMS. Suprathreshold vibration led to an increase in ICMS thresholds (median: 2.4 dB) but suprathreshold ICMS had little impact on vibrotactile thresholds. The ICMS-induced enhancement of vibrotactile sensitivity was location dependent with the effect size decreasing as the projected field of the stimulating electrode and the locus of vibratory stimulation became farther apart. These results demonstrate that targeted microstimulation of cortex alone can focally enhance tactile sensitivity, potentially enabling restoration or strengthening of retained tactile sensations after injury.
The association between rs6859 inNECTIN2gene and Alzheimer’s disease is partly mediated by pTau
Authors: Lathika Rajendrakumar Aravind , Arbeev Konstantin G. , Bagley Olivia , Yashin Anatoliy I. , Ukraintseva Svetlana 
Published: June 2024

AbstractIntroductionEmerging evidence suggests a connection between vulnerability to infections and Alzheimer’s disease (AD). The nectin cell adhesion molecule 2(NECTIN2)gene coding for a membrane component of adherens junctions is involved in response to infection, and its single nucleotide polymorphism (SNP) rs6859 was significantly associated with AD risk in several human cohorts. It is unclear, however, how exactly rs6859 influences the development of AD pathology. The aggregation of hyperphosphorylated tau protein (pTau) is a key pathological feature of neurodegeneration in AD, which may be induced by infections, among other factors, and potentially influenced by genes involved in both AD and vulnerability to infections, such asNECTIN2.Materials and methodsWe conducted a causal mediation analysis (CMA) on a sample of 708 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The relationship between rs6859 and Alzheimer’s disease (AD), with AD (yes/no) as the outcome and pTau-181 levels in the cerebrospinal fluid (CSF) acting as a mediator in this association, was assessed. Adjusted estimates from the probit and linear regression models were used in the CMA model, where an additive model considered an increase in dosage of the rs6859 A allele (AD risk factor).ResultsThe increase in dose of allele A of the SNP rs6859 resulted in about 0.144 increase per standard deviation (SD) of pTau-181 (95% CI: 0.041, 0.248, p<0.01). When included together in the probit model, the change in A allele dose and each standard deviation change in pTau-181 predicted 6.84% and 9.79% higher probabilities for AD, respectively. In the CMA, the proportion of the average mediated effect was 17.05% and was higher for the risk allele homozygotes (AA), at 19.40% (95% CI: 6.20%, 43.00%, p<0.01). The sensitivity analysis confirmed the evidence of a robust mediation effect.ConclusionThis study reported a new causal relationship between pTau-181 and AD. We found that the association between rs6859 in theNECTIN2gene and AD is partly mediated by pTau-181 levels in CSF. The rest of this association may be mediated by other factors. Further research, using other biomarkers, is needed to uncover the remaining mechanisms of the association between theNECTIN2gene and AD.
Bayesian Estimation Improves Prediction of Outcomes after Epilepsy Surgery
Authors: Dickey Adam S. , Reddy Vineet , Pedersen Nigel P. , Krafty Robert T. 
Published: June 2024

ABSTRACTLow power is a problem in many fields, as underpowered studies that find a statistically significant result will exaggerate the magnitude of the observed effect size. We quantified the statistical power and magnitude error of studies of epilepsy surgery outcomes. The median power across all studies was 14%. Studies with a median sample size or less (n<=56) and a statistically significant result exaggerated the true effect size by a factor of 5.4 (median odds ratio 9.3 vs. median true odds ratio 1.7), while the Bayesian estimate of the odds ratio only exaggerated the true effect size by a factor of 1.6 (2.7 vs. 1.7). We conclude that Bayesian estimation of odds ratio attenuates the exaggeration of significant effect sizes in underpowered studies. This approach could help improve patient counseling about the chance of seizure freedom after epilepsy surgery.SHORT SUMMARYWe estimated the statistical power of studies predicting seizure freedom after epilepsy surgery. We exacted data from a Cochrane meta-analysis. The median power across all studies was 14%. Studies with a median sample size or less (n<=56) and a statistically significant result exaggerated the true effect size by a factor of 5.4, while the Bayesian estimate of the odds ratio only exaggerated the true effect size by a factor of 1.6. We conclude that Bayesian estimation of odds ratios attenuates the exaggeration of significant effect sizes in underpowered studies. This result could improve patient counseling regarding epilepsy surgery.
Polygenic Risk Scores Provide Strong Evidence for the Biologic Relevance of Molecular Subtypes of Schizophrenia
Authors: Rhodes C. Harker , Granger Richard 
Published: June 2024

AbstractWe have previously described how the post-mortem DLPFC transcriptomes of schizophrenia patients can be used to define two patient groups: “Type 1” patients with a relatively normal DLPFC transcriptome and “Type 2” patients with hundreds of genes differentially expressed in the DLPFC at a statistical significance which survives Bonferroni correction. The biological significance of the distinction between Type 1 and Type 2 patients remains an open question. In the present report we examine the schizophrenia polygenic risk scores (PRS) in those two groups of schizophrenic patients and observe that PRS account for twice the variance in schizophrenia risk in the patients with a relatively normal DLPFC transcriptome (“Type 1”) compared to those with dramatically abnormal DLPFC transcriptomes (“Type 2”). That result supports the hypothesis that the DLPFC transcriptome-defined schizophrenia subtypes are biologically meaningful.As important as that result is, a serendipitous observation involving patient ancestry is potentially more important because it suggests an approach which future studies might use to investigate the pathogenic pathways leading to these two distinct forms of schizophrenia. Summary statistics from the Psychiatric Genetics Consortium (PGC) wave 3 core cohort GWAS data were used to calculate schizophrenia PRS. That cohort is composed primarily of Caucasians with about 13% Asians. It contains no Africans or African Americans. However, the cohort we studied here (the NIMH Human Brain Collection Core, or HBCC cohort) is composed of roughly 50% Caucasians and 50% African Americans. When the HBCC cohort is stratified based on ancestry it becomes obvious that in African Americans the polygenic risk scores based on summary statistics from the (Caucasian) PGC core cohort capture the genetic risk associated with Type 1, but not Type 2 schizophrenia. Future work comparing summary statistics from schizophrenia GWAS studies of Caucasian and African American populations should reveal the genes and genetic pathways which are specifically involved in the pathogenesis of the two types of schizophreniaDisclosuresThe opinions expressed herein are those of the authors and not necessarily representative of those of the Uniformed Services University of the Health Sciences (USU), the Department of Defense (DOD), the United States Army, Navy, Air Force, VA, NIH or any other US federal agency.