bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic pulmonary aspergillosis incidence in newly detected pulmonary tuberculosis cases during follow-up
Authors: Jha Dhouli , Kumar Umesh , Meena Ved Prakash , Sethi Prayas , Singh Amandeep , Nischal Neeraj , Jorwal Pankaj , Vyas Surabhi , Singh Gagandeep , Xess Immaculata , Singh Urvashi B , Sinha Sanjeev , Mohan Anant , Wig Naveet , Kabra Sushil Kumar , Ray Animesh 
Published: February 2024

AbstractBackgroundChronic pulmonary aspergillosis (CPA) is known to complicate patients with post-tubercular lung disease. However, some evidence suggests that CPA might co-exist in patients with newly-diagnosed pulmonary tuberculosis (P.TB) at diagnosis and also develop during therapy. The objective of this study was to confirm the presence of CPA in newly diagnosed P.TB at baseline and at end-of-therapy.Materials & MethodsThis prospective longitudinal study included newly diagnosed P.TB patients, followed up at third month and end-of-therapy with symptom assessment, anti-AspergillusIgG antibody and imaging of chest for diagnosing CPA.ResultsWe recruited 255 patients at baseline out of which 158 (62%) completed their follow-up. Anti-AspergillusIgG was positive in 11.1% at baseline and 27.8% at end-of-therapy. Overall, proven CPA was diagnosed in 7% at baseline and 14.5% at end-of-therapy. Around 6% patients had evidence of aspergilloma in CT chest at the end-of-therapy.ConclusionsCPA can be present in newly diagnosed P.TB patients at diagnosis and also develop during anti-tubercular treatment. Patients with persistent symptoms or developing new symptoms during treatment for P.TB should be evaluated for CPA.
What works to support better access to mental health services (from primary care to inpatients) for minority groups to reduce inequalities? A rapid evidence summary
Authors: Csontos Judit , Edwards Deborah , Gillen Elizabeth , Hounsome Juliet , Kiseleva Meg , Mann Mala , Sha’aban Abubakar , Lewis Ruth , Cooper Alison , Edwards Adrian 
Published: February 2024

AbstractIt is estimated that one in four people will experience poor mental health throughout their lifetimes. However, ethnic minority groups, refugees and asylum seekers experience more barriers accessing mental health services and have poorer mental health outcomes than those from non-ethnic minority groups. Evidence suggests that interventions that improve access and engagement with mental health services may help reduce disparities affecting ethnic minority groups, refugees and asylum seekers. Thus, the aim of this rapid evidence summary was to explore the literature on what works to support better access to mental health services for ethnic minority groups, refugees and asylum seekers to reduce inequalities. The review included interventions that were developed or assessed to improve equity in access, engagement, utilisation, or provision of mental health services.Research Implications and Evidence GapsThere is limited review evidence regarding the effectiveness of interventions to improve access to mental healthcare across ethnic minority groups. Review evidence regarding interventions to support refugees and asylum seekers access to primary healthcare or specialised clinics (for example pregnancy and postpartum) is available, but the findings related to mental health care cannot be extracted.
The FDA’s Proposed Rule on Laboratory-Developed Tests: Impacts on Clinical Laboratory Testing and Patient Care
Authors: Smith Leslie , Carricaburu Lisa A. , Genzen Jonathan R. 
Published: February 2024

ABSTRACTIn October 2023, the U.S. Food and Drug Administration (FDA) released a proposed rule to regulate laboratory-developed tests (LDTs) as medical devices. While approximately 6,700 public comments were submitted during the open comment period, there is not a reliable mechanism to quantify how clinical laboratorians as a sector perceive the proposed rule. To solicit quantifiable feedback on the FDA’s proposed rule, a ten-item questionnaire was developed and submitted to clinical laboratory customers of ARUP Laboratories, a national nonprofit clinical laboratory of the University of Utah Department of Pathology.Of 503 clinical laboratory respondents, only 41 (8.2%) support the FDA’s proposed rule. 66.9% of respondents work in laboratories that perform LDTs and were therefore asked additional questions regarding the proposed rule. 83.9% of these respondents believe that the proposed rule will negatively impact their laboratories, while only 3.0% believe that they have the financial resources to pay for FDA user fees. 60.9% of respondents anticipate removing tests from their laboratory menus if the proposed rule is enacted, while an additional 33.2% indicated that they do not yet know. Only 11.2% of respondents believe that they would pursue FDA submissions for all of their existing LDTs if the final rule is enacted.The vast majority of respondents (>80%) were either ‘extremely concerned’ or ‘very concerned’ about the impact of the proposed rule on patient access to essential testing, financial and personnel resources to comply, innovation, the FDA’s ability to implement the proposed rule, and send-out costs and test prices. Respondents indicated that they would rely heavily on reference laboratory partners for advocacy against the proposed rule, testing options, education, and consultation if the rule was enacted. Thematic analysis of open comments revealed strong opposition to the proposed rule and significant concern regarding negative impacts to patient care across clinical laboratory settings.
Effect of neonatal BCG vaccination on the evolution of Hashimoto’s Thyroiditis
Authors: Agrawal Kanhaiya , Basak Preetam , Badal Darshan , Dutta Pinaki , Walia Rama , Sachdeva Naresh 
Published: February 2024

ABSTRACTBackgroundHashimoto’s thyroiditis (HT) involves the autoimmune destruction of thyrocytes with the presence of anti-thyroid peroxidase (TPO) and/or anti-thyroglobulin (TG) antibodies. In autoimmune diseases, an immunomodulatory role of Bacillus Calmette-Guerin (BCG) vaccination has been reported with decreased autoantibody production and induction of regulatory T cells. We hypothesize that a decline in the efficacy of BCG might be associated with the appearance of HT during adulthood.MethodsAdult subjects with subclinical HT (HT-SCH) (n=39) and non-autoimmune subclinical hypothyroidism (NA-SCH) (n=25) were enrolled along with euthyroid healthy controls (HC) (n=20). The BCG-specific immune responses were determined by the Mantoux test and BCG-induced in-vitro proliferation of peripheral blood mononuclear cells (PBMC). Anti-thyroid cellular immune responses were assessed in subjects with human leukocyte antigen (HLA)-A*02 and HLA-A*24 alleles by determining the frequency of CD8+ T cells recognizing major histocompatibility complex (MHC) dextramers (DMR) carrying TPO-derived peptides, by flow cytometry.ResultsThe HT-SCH group had a lower rate of Mantoux test reactivity (38.5%) as compared to NA-SCH (64%) and HC subjects (65%) (p=0.047). However, the BCG-induced in-vitro proliferation of PBMC was similar in HT-SCH, NA-SCH, and HC groups. Further, the BCG-vaccinated SCH subjects had lower levels of thyroid stimulating hormone (TSH) (p=0.026). Next, the SCH subjects had higher frequencies of peripheral DMR+ CD8+ T cells as compared to HC subjects (p=0.001). Interestingly, the frequency of peripheral DMR+ CD8+ T cells was significantly higher in HT-SCH than HC subjects (p=0.045). Finally, we observed a positive correlation between the frequency of DMR+CD8+ T cells and TSH levels (r = +0.620, p=0.006).ConclusionsCollectively, our results highlight a complex relationship of neonatal BCG vaccination with the genesis of HT, via modulation of autoimmune responses directed towards thyroid autoantigens.
Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta
Authors: Conrad William S. , Oriol Lucie , Kollman Grace J. , Faget Lauren , Hnasko Thomas S. 
Published: February 2024

ABSTRACTMost studies on the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) have focused on dopamine neurons and their role in processes such as motivation, learning, movement, and associated disorders such as addiction and Parkinson’s disease. However there has been increasing attention on other VTA and SNc cell types that release GABA, glutamate, or a combination of neurotransmitters. Yet the relative distributions and proportions of neurotransmitter-defined cell types across VTA and SNc has remained unclear. Here, we used fluorescent in situ hybridization in male and female mice to label VTA and SNc neurons that expressed mRNA encoding the canonical vesicular transporters for dopamine, GABA, or glutamate: vesicular monoamine transporter (VMAT2), vesicular GABA transporter (VGAT), and vesicular glutamate transporter (VGLUT2). Within VTA, we found that no one type was particularly more abundant, instead we observed similar numbers of VMAT2+ (44%), VGAT+ (37%) and VGLUT2+ (41%) neurons. In SNc we found that a slight majority of neurons expressed VMAT2 (54%), fewer were VGAT+ (42%), and VGLUT2+ neurons were least abundant (16%). Moreover, 20% of VTA neurons and 10% of SNc neurons expressed more than one vesicular transporter, including 45% of VGLUT2+ neurons. We also assessed within VTA and SNc subregions and found remarkable heterogeneity in cell-type composition. And by quantifying density across both anterior-posterior and medial-lateral axes we generated heatmaps to visualize the distribution of each cell type. Our data complement recent single-cell RNAseq studies and support a more diverse landscape of neurotransmitter-defined cell types in VTA and SNc than is typically appreciated.
Novel misos shape distinct microbial ecologies: opportunities for flavourful sustainable food innovation
Authors: Kothe Caroline Isabel , Carøe Christian , Mazel Florent , Zilber David , Cruz-Morales Pablo , Mohellibi Nacer , Evans Joshua 
Published: February 2024

AbstractFermentation is resurgent around the world as people seek healthier, more sustainable, and tasty food options. This study explores the microbial ecology of miso, a traditional Japanese fermented paste, made with novel regional substrates to develop new plant-based foods. Eight novel miso varieties were developed using different protein-rich substrates: yellow peas, Gotland lentils, and fava beans (each with two treatments: standard and nixtamalisation), as well as rye bread and soybeans. The misos were produced at Noma, a restaurant in Copenhagen, Denmark. Samples were analysed with biological and technical triplicates at the beginning and end of fermentation. We also incorporated in this study six samples of novel misos produced following the same recipe at Inua, a former affiliate restaurant of Noma in Tokyo, Japan. To analyse microbial community structure and diversity, metabarcoding (16S and ITS) and shotgun metagenomic analyses were performed. The misos contain a greater range of microbes than is currently described for miso in the literature. The composition of the novel yellow pea misos was notably similar to the traditional soybean ones, suggesting they are a good alternative, which supports our culinary collaborators’ sensory conclusions. For bacteria, we found that overall substrate had the strongest effect, followed by time, treatment (nixtamalisation), and geography. For fungi, there was a slightly stronger effect of geography and a mild effect of substrate, and no significant effects for treatment or time. Based on an analysis of metagenome-assembled genomes (MAGs), strains ofS. epidermidisdifferentiated according to substrate. Carotenoid biosynthesis genes in these MAGs appeared in strains from Japan but not from Denmark, suggesting a possible gene-level geographical effect. The benign and possibly functional presence ofS. epidermidisin these misos, a species typically associated with the human skin microbiome, suggests possible adaptation to the miso niche, and the flow of microbes between bodies and foods in certain fermentation as more common than is currently recognised. This study improves our understanding of miso ecology, highlights the potential for developing novel misos using diverse local ingredients, and suggests how fermentation innovation can contribute to studies of microbial ecology and evolution.
CyanoTag: Discovery of protein function facilitated by high-throughput endogenous tagging in a photosynthetic prokaryote
Authors: Perrin Abigail J. , Dowson Matthew , Dowle Adam A. , Calder Grant , Springthorpe Victoria J. , Zhao Guoyan , Mackinder Luke C. M. 
Published: February 2024

AbstractDespite their fundamental importance to aquatic ecosystems, global carbon cycling and exciting potential in sustainable bioindustries, the genomes of photosynthetic prokaryotes still contain large numbers of uncharacterised protein-coding genes. Here we present a high-throughput approach for scarless endogenous fluorescent protein tagging in the model cyanobacteriumSynechococcus elongatusPCC7942. From 400 targets we successfully endogenously tag over 330 proteins corresponding to >10% of the proteome. We demonstrate how this resource can be used at scale to determine subcellular localisation, track relative protein abundances and to elucidate protein-protein interaction networks. Our data has provided biological insights into a diverse range of processes - from photosynthesis to cell division. Of particular interest, our ‘CyanoTag’ lines enabled us to visualise in real time the rapid condensation of Calvin Cycle proteins Prk and Gap2 within seconds of withdrawal of light, effectively ‘switching off’ photosynthesis in the dark. These insights, CyanoTag cell lines, associated data and optimised methods are intended to be shared as a resource to facilitate further discoveries relevant to cyanobacteria and more broadly to all photosynthetic life.
Pathway-enhanced Transformer-based robust model for quantifying cell types of origin of cell-free transcriptome
Authors: Yan Shuo , Tian Xuetao , Qin Yulong , Li Jiayi , Yang Tingyu , Yu Dongyue , Liu Wentao , Sun Jinghua , Hu Chengbin , Zhou Qing , Liu Zhongzhen , Wang Wen-Jing 
Published: February 2024

AbstractAnalyzing cell types of origin of cell-free RNA can enhance the resolution of liquid biopsies, thereby deepening the understanding of molecular and cellular changes in development and disease processes. Existing deconvolution methods typically rely on meticulously curated gene expression profiles or employ deep neural network with vast and complex solution spaces that are difficult to interpret. These approaches overlook the synergistic and co-expression effects among genes in biological signaling pathways, compromising their generalizability and robustness. we developed ‘Deconformer’, a Transformer-based deconvolution model that integrates biological signaling pathways at the embedding stage, to address these issues. Compared to popular methods on multiple datasets, Deconformer demonstrates superior performance and robustness, and is capable of tracking the developmental process of the fetal and placenta. Additionally, pathway-level interpretability of Deconformer offers new insights into crosstalk, dependencies, and other interactions within cell-free RNA pathways, supporting further biological discoveries. We posit that Deconformer represents a significant advancement in the precise analysis of the cell-free transcriptome. It holds the promise of describing disease progression and severity with a new level of accuracy, focusing on the contributions of originating cell types and their pathway dependencies. This model has the potential to catalyze the development of non-invasive diagnostic tools and enhance our understanding of the underlying biology of diseases.
Statistical learning of incidental perceptual regularities induces sensory conditioned cortical responses
Authors: Greco Antonino , D’Alessandro Marco , Gallitto Giuseppe , Rastelli Clara , Braun Christoph , Caria Andrea 
Published: February 2024

ABSTRACTStatistical learning of sensory patterns can lead to predictive neural processes enhancing stimulus perception and enabling fast deviancy detection. Predictive processes have been extensively demonstrated when environmental statistical regularities are relevant to task execution. Preliminary evidence indicates that statistical learning can even occur independently of task relevance and top-down attention, although the temporal profile and neural mechanisms underlying sensory predictions and error signals induced by statistical learning of incidental sensory regularities remain unclear. In our study, we adopted an implicit sensory conditioning paradigm that elicited the generation of specific perceptual priors in relation to task-irrelevant audio-visual associations, while recording Electroencephalography (EEG). Our results showed that learning of non-relevant but statistically interrelated neutral audio-visual stimuli resulted in early neural responses to predictive auditory stimuli conveying anticipatory signals of expected visual stimulus presence or absence, and in specific modulation of cortical responses to probabilistic visual stimulus presentation or omission. Pattern similarity analysis indicated that predictive auditory stimuli tended to resemble the response to expected visual stimulus presence or absence. Remarkably, Hierarchical Gaussian filter modeling estimating dynamic changes of prediction error signals in relation to differential probabilistic occurrences of audio-visual stimuli further demonstrated instantiation of predictive neural signals by showing distinct neural processing of prediction error in relation to violation of expected visual stimulus presence or absence. Overall, our findings indicated that statistical learning of non-salient and task-irrelevant perceptual regularities can induce the generation of neural priors at the time of predictive stimulus presentation, possibly conveying sensory-specific information of the predicted consecutive stimulus.
Diet-induced metabolic and immune impairments are sex-specifically modulated by soluble TNF signaling in the 5xFAD mouse model of Alzheimer’s disease
Authors: De Sousa Rodrigues Maria Elizabeth , Bolen MacKenzie L. , Blackmer-Raynolds Lisa , Schwartz Noah , Chang Jianjun , Tansey Malú Gámez , Sampson Timothy Robert 
Published: February 2024

AbstractEmerging evidence indicates that high-fat, high carbohydrate diet (HFHC) impacts central pathological features of Alzheimer’s disease (AD) across both human incidences and animal models. However, the mechanisms underlying this association are poorly understood. Here, we identify compartment-specific metabolic and inflammatory dysregulations that are induced by HFHC diet in the 5xFAD mouse model of AD pathology. We observe that both male and female 5xFAD mice display exacerbated adiposity, cholesterolemia, and dysregulated insulin signaling. Independent of biological sex, HFHC diet also resulted in altered inflammatory cytokine profiles across the gastrointestinal, circulating, and central nervous systems (CNS) compartments demonstrating region-specific impacts of metabolic inflammation. In male mice, we note that HFHC triggered increases in amyloid beta, an observation not seen in female mice. Interestingly, inhibiting the inflammatory cytokine, soluble tumor necrosis factor (TNF) with the brain-permeant soluble TNF inhibitor XPro1595 was able to restore aspects of HFHC-induced metabolic inflammation, but only in male mice. Targeted transcriptomics of CNS regions revealed that inhibition of soluble TNF was sufficient to alter expression of hippocampal and cortical genes associated with beneficial immune and metabolic responses. Collectively, these results suggest that HFHC diet impairs metabolic and inflammatory pathways in an AD-relevant genotype and that soluble TNF has sex-dependent roles in modulating these pathways across anatomical compartments. Modulation of energy homeostasis and inflammation may provide new therapeutic avenues for AD.HighlightsHFHC diet triggers metabolic and inflammatory dysregulation in 5xFAD miceAβ42 and Aβ40 increase in the CNS of male 5xFAD mice fed a HFHC diet.SolTNF inhibition partially reverts HFHC diet-induced metabolic and inflammatory dysregulation in male, but not female, 5xFAD mice.
Circulating plasma fibronectin affects normal adipose tissue insulin sensitivity and adipocyte differentiation
Authors: Mahmoodi Mahdokht , Dahagi Elahe Mirzarazi , Nabavi Mir-Hamed , Penalva Ylauna , Gosaine Amrita , Murshed Monzur , Couldwell Sandrine , Munter Lisa , Kaartinen Mari T. 
Published: February 2024

AbstractPlasma fibronectin (pFN), a liver-derived, circulating protein, has been shown to affect adipocyte morphology, adipogenesis, and insulin signalling in preadipocytesin vitro. In this study, we show via injections of fluorescence-labelled pFN to micein vivoits abundant accrual visceral and subcutaneous adipose tissues (VAT and SAT). Diet-induced obesity model of liver-specific conditionalFn1knockout (pFN KO), showed no altered weight gain or differences, whole-body fat mass or SAT or VAT volumes after 20- week HFD-feeding, however, mice showed significantly improved glucose clearance and whole-body insulin sensitivity on normal diet. Furthermore,in vivoinsulin sensitivity assay revealed significant increase in AKT phosphorylation in pFN KO SAT on normal diet as well as in normal and obese VAT of the pFN KO. Histological assessment of the pFN KO depots showed significant increase in small adipocytes on normal diet, which was particularly prominent in SAT. RNA sequencing of the normal diet-fed pFN versus control SAT revealed alterations in fatty acid metabolism and thermogenesis suggesting presence of beige adipocytes. VAT RNA sequencing after HFD showed alternations in genes reflecting stem cell populations. Our data suggests that the absence of pFN alters cell pools in AT favoring cells with increased insulin sensitivity.
A Lung Cancer Mouse Model Database
Authors: Cai Ling , Gao Ying , DeBerardinis Ralph J. , Acquaah-Mensah George , Aidinis Vassilis , Beane Jennifer E. , Biswal Shyam , Chen Ting , Concepcion-Crisol Carla P. , Grüner Barbara M. , Jia Deshui , Jones Robert , Kurie Jonathan M. , Lee Min Gyu , Lindahl Per , Lissanu Yonathan , Lorz Lopez Maria Corina , Martinelli Rosanna , Mazur Pawel K. , Mazzilli Sarah A. , Mii Shinji , Moll Herwig , Moorehead Roger , Morrisey Edward E. , Ng Sheng Rong , Oser Matthew G. , Pandiri Arun R. , Powell Charles A. , Ramadori Giorgio , Santos Lafuente Mirentxu , Snyder Eric , Sotillo Rocio , Su Kang-Yi , Taki Tetsuro , Taparra Kekoa , Xia Yifeng , van Veen Ed , Winslow Monte M. , Xiao Guanghua , Rudin Charles M. , Oliver Trudy G. , Xie Yang , Minna John D. 
Published: February 2024

AbstractLung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. Here we established the Lung Cancer Mouse Model Database (LCMMDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMMs), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors have produced a robust and comprehensive database, enhancing the fidelity of the genetic landscape it depicts. The LCMMDB aligns 859 tumors from GEMMs with human lung cancer mutations, enabling comparative analysis and revealing a pressing need to broaden the diversity of genetic aberrations modeled in GEMMs. Accompanying this resource, we developed a web application that offers researchers intuitive tools for in-depth gene expression analysis. With standardized reprocessing of gene expression data, the LCMMDB serves as a powerful platform for cross-study comparison and lays the groundwork for future research, aiming to bridge the gap between mouse models and human lung cancer for improved translational relevance.