bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tau PET visual reads find sources of tau not explained by typical Alzheimer disease pathophysiology
Authors: Chen Charles D. , Ponisio Maria Rosana , Lang Jordan A. , Flores Shaney , Schindler Suzanne E. , Fagan Anne M. , Morris John C. , Benzinger Tammie L.S. 
Published: December 2022

Abstract18F-flortaucipir-PET received FDA approval to visualize tauopathy in the brains of adult patients with cognitive impairment being evaluated for Alzheimer disease (AD). However, manufacturer’s guidelines for the visual interpretation of18F-flortaucipir-PET differs greatly from how18F-flortaucipir-PET has been measured in research settings using standardized uptake value ratios (SUVRs). How visual interpretation relates to18F-flortaucipir-PET SUVR, CSF biomarkers, or longitudinal clinical assessment is not well understood. Here we compare these various diagnostic methods in participants enrolled in studies of aging and memory (n=189, of whom 23 were cognitively impaired). Visual interpretation had high agreement with SUVR (98.4%); discordant participants had hemorrhagic infarcts or atypical AD tauopathies. Visual interpretation had moderate agreement with CSF p-tau181 (86.1%). Two participants demonstrated18F-flortaucipir uptake from meningiomas. Visual interpretation could not predict follow-up clinical assessment in 9.52% of cases. We conclude that close association between AD tauopathy and clinical onset in group-level studies does not always hold at the individual level, with discrepancies arising from atypical AD, vascular dementia, or frontotemporal dementia. A better understanding of relationships across imaging, CSF biomarkers, and clinical assessment is needed to provide appropriate diagnoses for these individuals.
Effect of a brief psychological intervention for common mental disorders on HIV viral suppression: a non-randomised controlled study of the Friendship Bench in Zimbabwe
Authors: Simms Victoria , Abas Melanie A , Müller Monika , Munetsi Epiphania , Dzapasi Lloyd , Weiss Helen A , Chibanda Dixon 
Published: December 2022

AbstractBackgroundFor people living with co-morbid HIV and common mental disorders (CMD), it is not known whether a brief psychological intervention for CMD can improve HIV viral suppression.MethodsWe conducted a prospective cohort study in eight primary care clinics in Harare, Zimbabwe, enrolling adults with co-morbid HIV and CMD. Six clinics provided the Friendship Bench (FB), a brief psychological intervention for CMD based on problem-solving therapy, delivered by lay counsellors. Two clinics provided enhanced usual care (EUC). The primary outcome was viral non-suppression after six months (viral load ≥400 copies/mL). Data were analysed using a difference-in-difference approach with linear regression of cluster-level proportions, adjusted for baseline viral non-suppression (aDiD). The secondary outcome was presence of CMD measured by the Shona Symptom Questionnaire.ResultsIn FB clinics, 407/500 (81.4%) participants had viral load results at baseline and endline: 58 (14.3%) had viral non-suppression at baseline and 41 (10.1%) at endline. In EUC clinics, 172/200 (86.0%) had viral load results at baseline and endline: 22 (12.8%) were non-suppressed at baseline and 26 (15.1%) at endline (aDiD= -7.3%; 95%CI 14.7% to -0.01%; p=0.05). Of the 499 participants virally suppressed at baseline, the FB group had lower prevalence of non-suppression at endline compared to the EUC group (2.9% vs 9.3%; p=0.002). There was no evidence of a difference in endline viral non-suppression by group among the 80 participants with non-suppression at baseline (53.5% vs 54.6%; p=0.93). The FB group were less likely to screen positive for CMD at endline than the EUC group (aDiD= -21.6%; 95%CI -36.5% to -6.7%; p=0.008).ConclusionPeople living with co-morbid HIV and CMD may benefit from receiving a low-cost mental health intervention to enhance viral suppression, especially if they are already virally suppressed. Research is needed to understand if additional adherence counselling could further improve viral suppression.
Lab evolution, transcriptomics, and modeling reveal mechanisms of paraquat tolerance
Authors: Rychel Kevin , Tan Justin , Patel Arjun , Lamoureux Cameron , Hefner Ying , Szubin Richard , Johnsen Josefin , Mohamed Elsayed Tharwat Tolba , Phaneuf Patrick V. , Anand Amitesh , Olson Connor A. , Park Joon Ho , Sastry Anand V. , Yang Laurence , Feist Adam M. , Palsson Bernhard O. 
Published: December 2022

SummaryRelationships between the genome, transcriptome, and metabolome underlie all evolved phenotypes. However, it has proved difficult to elucidate these relationships because of the high number of variables measured. A recently developed data analytic method for characterizing the transcriptome can simplify interpretation by grouping genes into independently modulated sets (iModulons). Here, we demonstrate how iModulons reveal deep understanding of the effects of causal mutations and metabolic rewiring. We use adaptive laboratory evolution to generateE. colistrains that tolerate high levels of the redox cycling compound paraquat, which produces reactive oxygen species (ROS). We combine resequencing, iModulons, and metabolic models to elucidate six interacting stress tolerance mechanisms: 1) modification of transport, 2) activation of ROS stress responses, 3) use of ROS-sensitive iron regulation, 4) motility, 5) broad transcriptional reallocation toward growth, and 6) metabolic rewiring to decrease NADH production. This work thus reveals the genome-scale systems biology of ROS tolerance.Graphical Abstract
An at-home and electro-free COVID-19 rapid test based on colorimetric RT-LAMP
Authors: Tran Diem Hong , Tran Hau Thi , Pham Trang Nguyen Minh , Bui Le Minh , Phung Huong Thi Thu 
Published: December 2022

AbstractPurposeIn the fight against virus-caused pandemics like COVID-19, the use of diagnostic tests based on RT-qPCR is essential but sometimes limited by their dependence on expensive, specialized equipment and skilled personnel. Consequently, an alternative nucleic acid detection technique that gets over these restrictions, called loop-mediated isothermal amplification following reverse transcription (RT-LAMP), has been broadly investigated. Nevertheless, the developed RT-LAMP assays for SARS-CoV-2 detection still require laboratory devices and are electrically dependent, limiting their widespread use as rapid home tests. In this work, a flexible RT-LAMP assay that gets beyond the drawbacks of the available isothermal LAMP-based SARS-CoV-2 detection was developed, establishing a simple and effective at-home diagnosis tool for COVID-19.MethodsA multiplex direct RT-LAMP assay modified from the previously developed test was applied to simultaneously identify the two genes of SARS-CoV-2. We used a colorimetric readout, lyophilized reagents, and benchmarked an electro-free and micropipette-free method that enables sensitive and specific detection of SARS-CoV-2 in home settings.ResultsForty-one nasopharyngeal swab samples were tested using the home-testing RT-LAMP (HT-LAMP) assay developed, showing 100% agreement with the RT-qPCR results.ConclusionsThis is the first electrically independent RT-LAMP assay successfully developed for SARS-CoV-2 detection at home setting. Our HT-LAMP assay is thus an important development for diagnosing COVID-19 or any other infectious pandemic on a population scale.
Psychiatric Residential Treatment Facilities for Child Behavioral Health Services in North Carolina Medicaid
Authors: Lanier Paul , Rose Roderick , Gibbs Daniel , Hyman Jacob , Kamdar Neil , Konstanzer Joseph , Lich Kristen Hassmiller 
Published: December 2022

AbstractBackgroundPsychiatric residential treatment facilities (PRTFs) are a type of non-hospital inpatient treatment setting for children with severe behavioral health disorders. PRTFs are a restrictive and costly form of care that can potentially be avoided with community-based behavioral health services.MethodStatewide Medicaid enrollment and claims data for 2015 to 2022 were used to describe PRTF utilization in North Carolina. We examined annual episodes of care in PRTFs and compared trends before and during the COVID-19 public health emergency.ResultsFrom 2015 to 2022, 10,038 children insured by North Carolina Medicaid entered a PRTF across 10,966 episodes of care. In the past five years (2018-2022), care in PRTFs resulted in Medicaid expenditures of over $550 million total, or over $100 million per year. In 2022, 42% of children who entered PRTFs were in foster care and 44% of children were placed in PRTFs outside of North Carolina.LimitationsAnalysis limited to data collected for administrative purposes.ConclusionsCurrent trends indicate ongoing overrepresentation of children in foster care placed in PRTFs and increased out-of-state PRTF placements. Coordinated efforts in future research, policy, and practice are needed to determine the cause of these trends and identify solutions.
Collective Intelligent Strategy for Improved Segmentation of COVID-19 from CT
Authors: Das Surochita Pal , Mitra Sushmita , Shankar B. Uma 
Published: December 2022

AbstractThe devastation caused by the coronavirus pandemic makes it imperative to design automated techniques for a fast and accurate detection. We propose a novel non-invasive tool, using deep learning and imaging, for delineating COVID-19 infection in lungs. The Ensembling Attention-based Multi-scaled Convolution network (EAMC), employing Leave-One-Patient-Out (LOPO) training, exhibits high sensitivity and precision in outlining infected regions along with assessment of severity. The Attention module combines contextual with local information, at multiple scales, for accurate segmentation. Ensemble learning integrates heterogeneity of decision through different base classifiers. The superiority of EAMC, even with severe class imbalance, is established through comparison with existing state-of-the-art learning models over four publicly-available COVID-19 datasets. The results are suggestive of the relevance of deep learning in providing assistive intelligence to medical practitioners, when they are overburdened with patients as in pandemics. Its clinical significance lies in its unprecedented scope in providing low-cost decision-making for patients lacking specialized healthcare at remote locations.
Polarity-driven three-dimensional spontaneous rotation of a cell doublet
Authors: Lu Linjie , Guyomar Tristan , Vagne Quentin , Berthoz Rémi , Torres-Sánchez Alejandro , Lieb Michèle , Martin-Lemaitre Cecilie , van Unen Kobus , Honigmann Alf , Pertz Olivier , Salbreux Guillaume , Riveline Daniel 
Published: December 2022

AbstractCell mechanical interactions play a fundamental role in the self-organisation of organisms. How these interactions drive coordinated cell movement in three-dimensions remains unclear. Here we report that cell doublets embedded in a 3D extracellular matrix undergo spontaneous rotations and we investigate the rotation mechanism using live cell imaging, quantitative measurements, mechanical perturbations, and theory. We find that rotation is driven by a polarized distribution of myosin within cell cortices. The mismatched orientation of this polarized distribution breaks the doublet mirror symmetry. In addition, cells adhere at their interface through adherens junctions and with the extracellular matrix through focal contacts near myosin clusters. Using a physical theory describing the doublet as two interacting active surfaces, we find that rotation is driven by myosin-generated gradients of active tension, whose profiles are dictated by interacting cell polarity axes. We show that interface three-dimensional shapes can be understood from the Curie principle: shapes symmetries are related to broken symmetries of myosin distribution in cortices. To test for the rotation mechanism, we suppress myosin clusters using laser ablation and we generate new myosin clusters by optogenetics. Our work clarifies how polarity-oriented active mechanical forces drive collective cell motion in three dimensions.
T-cell cellular stress and reticulocyte signatures, but not loss of naïve T lymphocytes, characterize severe COVID-19 in older adults
Authors: Jergović Mladen , Watanabe Makiko , Bhat Ruchika , Coplen Christopher P. , Sonar Sandip A. , Wong Rachel , Castaneda Yvonne , Davidson Lisa , Kala Mrinalini , Wilson Rachel C. , Twigg Homer L. , Knox Kenneth , Erickson Heidi E. , Weinkauf Craig C. , Bime Christian , Bixby Billie A. , Parthasarathy Sairam , Mosier Jarrod M. , LaFleur Bonnie J. , Bhattacharya Deepta , Nikolich Janko Ž. 
Published: December 2022

AbstractIn children and younger adults up to 39 years of age, SARS-CoV-2 usually elicits mild symptoms that resemble the common cold. Disease severity increases with age starting at 30 and reaches astounding mortality rates that are ~330 fold higher in persons above 85 years of age compared to those 18-39 years old.To understand age-specific immune pathobiology of COVID-19 we have analyzed soluble mediators, cellular phenotypes, and transcriptome from over 80 COVID-19 patients of varying ages and disease severity, carefully controlling for age as a variable. We found that reticulocyte numbers and peripheral blood transcriptional signatures robustly correlated with disease severity. By contrast, decreased numbers and proportion of naïve T-cells, reported previously as a COVID-19 severity risk factor, were found to be general features of aging and not of COVID-19 severity, as they readily occurred in older participants experiencing only mild or no disease at all. Single-cell transcriptional signatures across age and severity groups showed that severe but not moderate/mild COVID-19 causes cell stress response in different T-cell populations, and some of that stress was unique to old severe participants, suggesting that in severe disease of older adults, these defenders of the organism may be disabled from performing immune protection. These findings shed new light on interactions between age and disease severity in COVID-19.
À la carte,Streptococcus pneumoniaecapsular typing: using MALDI-TOF mass spectrometry and machine learning algorithms as complementary tools for the determination of PCV13 serotypes and the most prevalent NON PCV13 serotypes according to Argentina’s epidemiology
Authors: Zintgraff Jonathan , Rocca Florencia , Eluchans Nahuel Sánchez , Irazu Lucía , Moscoloni Maria Luisa , Lara Claudia , Santos Mauricio 
Published: December 2022

ABSTRACTLaboratory surveillance ofStreptococcus pneumoniaeserotypes is crucial for the successful implementation of vaccines to prevent invasive pneumococcal diseases. The reference method of serotyping is the Quellung reaction, which is labor-intensive and expensive.In the last few years, the introduction of MALDI-TOF MS into the microbiology laboratory has been revolutionary. In brief, this new technology compares protein profiles by generating spectra based on the mass to charge ratio (m/z).We evaluated the performance of MALDI-TOF MS for typing serotypes ofS. pneumoniaeisolates included in the PCV13 vaccine using a machine learning approach. We challenged our classification algorithms in “real time” with a total of new 100 isolates ofS. pneumoniaefrom Argentinian nationwide surveillance.Our best approach could correctly identify the isolates with a sensitivity of 58.33 % ([95%IC 40.7-71.7]); specificity of 81.48 % ([95%IC 53.6-79.7]); accuracy of 63.0% ([95%IC 61.9-93.7]); PPV of 80.77% ([95%IC 64.5-90.6]) and NPV of 59.46% ([95%IC 48.9-69.2]).In this work, it was possible to demonstrate that the combination of MALDI-TOF mass spectrometry and multivariate analysis allows the development of new strategies for the identification and characterization of Spn isolates of clinical importance; and we consider that by using AI, as more data becomes available the models will get better and more precise.
Three linked opposing regulatory variants under selection associate withIVD
Authors: Brown Elizabeth A. , Kales Susan , Boyle Michael J. , Vitti Joseph , Kotliar Dylan , Schaffner Stephen F. , Tewhey Ryan S. , Sabeti Pardis C. 
Published: December 2022

ABSTRACTWhile genome-wide association studies (GWAS) and selection scans identify genomic loci driving human phenotypic diversity, functional validation is required to discover the variant(s) responsible. We dissected theIVDlocus, implicated by selection statistics, multiple GWAS, and clinical genetics as important to function and fitness. We combined luciferase assays, CRISPR/Cas9 genome-editing, massively parallel reporter assays (MPRA), and bashing of regulatory loci. We identified three regulatory variants, including an indel, that may underpin GWAS signals for pulmonary fibrosis and testosterone, and that are linked on a positively selected haplotype in the Japanese population. These regulatory variants exhibit synergistic and opposing effects onIVDexpression experimentally. Alleles at these variants lie on a haplotype tagged by the variant most strongly associated withIVDexpression and metabolites, but with no functional evidence itself. This work demonstrates how comprehensive functional investigation and multiple technologies are needed to discover the true genetic drivers of phenotypic diversity.
Cleavage furrow-directed cortical flows bias mechanochemical pathways for PAR polarization in theC. elegansgerm lineage
Authors: Ng KangBo , Hirani Nisha , Bland Tom , Borrego-Pinto Joana , Goehring Nathan W. 
Published: December 2022

AbstractDuring development, the conserved PAR polarity network is continuously redeployed, requiring that it adapts to changing cellular contexts and environmental cues. How it does so and the degree to which these adaptations reflect changes in its fundamental design principles remain unclear. Here, we investigate the process of PAR polarization within the highly tractableC. elegansgermline P lineage, which undergoes a series of iterative asymmetric stem cell-like divisions. Compared to the zygote, we observe significant differences in the pattern of polarity emergence, including an inversion of the initial unpolarized state, changes in symmetry breaking cues, and the timings with which anterior and posterior PARs segregate. Beneath these differences, however, polarity establishment remains reliant on the same core pathways identified in the zygote, including conserved roles for cortical actin flows and PAR-dependent self-organization. Intriguingly, we find that cleavage furrow-directed cortical actin flows play a similar symmetry-breaking role for the germline cell P1 as centrosome-induced cortical flows in the zygote. Through their ability to induce asymmetric accumulation of PAR-3 clusters, these furrow-directed flows directly couple the geometry of polarization to cell division, which could be a general strategy for cells to ensure proper organization within dynamically growing systems, such as embryos. In summary, our data suggest that coupling of novel symmetry-breaking cues with highly adaptable core mechanochemical circuits enable robust PAR polarity in response to changing developmental contexts.
An optimized approach for multiplexing single-nuclear ATAC-seq using oligonucleotide conjugated antibodies
Authors: Bera Betelehem Solomon , Thompson Taylor V. , Sosa Eric , Nomaru Hiroko , Reynolds David , Dubin Robert A. , Maqbool Shahina B. , Zheng Deyou , Morrow Bernice E. , Greally John M. , Suzuki Masako 
Published: December 2022

AbstractBackgroundSingle-cell technologies to analyze transcription and chromatin structure have been widely used in many research areas to reveal the functions and molecular properties of cells at single-cell resolution. Sample multiplexing techniques are valuable when performing single-cell analysis, reducing technical variation and permitting cost efficiencies. Several commercially available methods are available and have been used in many scRNA-seq studies. On the other hand, while several methods have been published, the multiplexing techniques for single nuclear Assay for Transposase-Accessible Chromatin (snATAC)-seq assays remain under development. We developed a simple nucleus hashing method using oligonucleotide conjugated antibodies recognizing nuclear pore complex proteins, NuHash, to perform snATAC-seq library preparations by multiplexing.ResultsWe performed multiplexing snATAC-seq analyses on the mixture of human and mouse cell samples (two samples, 2-plex, and four samples, 4-plex) using NuHash. The demultiplexing accuracy of NuHash was high, and only ten out of 9,144 nuclei (2-plex) and 150 of 12,208 nuclei (4-plex) had discordant classifications between NuHash demultiplexing and discrimination using reference genome alignments. We compared results between snATAC-seq and deeply sequenced bulk ATAC-seq on the same samples and found that most of the peaks detected in snATAC-seq were also detected in deeply sequenced bulk ATAC-seq. The bulk ATAC-seq signal intensity was positively correlated with the number of cell subtype clusters detected in snATAC-seq, but not the subset of peaks detected in all clusters. These subsets of snATAC-seq peaks showed different distributions over different genomic features, suggesting that the peak intensities of bulk ATAC-seq can be used to identify different types of functional loci.ConclusionsOur multiplexing method using oligo-conjugated anti-nuclear pore complex proteins, NuHash, permits high accuracy demultiplexing of samples. The NuHash protocol is straightforward, it works on frozen samples, and requires no modifications for snATAC-seq library preparation.
Murine Vaginal Co-infection with Penicillinase-ProducingNeisseria gonorrhoeaeFails to Alleviate Amoxicillin-Induced Chlamydial Persistence
Authors: Onorini Delia , Leonard Cory Ann , Pesch Theresa , Prähauser Barbara , Schoborg Robert V. , Borel Nicole 
Published: December 2022

ABSTRACTChlamydia trachomatis(CT) andNeisseria gonorrhoeae(NG) cause most bacterial sexually transmitted infections (STIs) worldwide. CT/NG co-infection is more common than expected due to chance, suggesting CT/NG interaction. However, CT/NG co-infection remains largely unstudied. Obligate intracellular CT has a characteristic biphasic developmental cycle consisting of two bacterial forms, infectious elementary bodies (EBs) and non-infectious, replicating reticulate bodies (RBs), which reside within host-derived, membrane-bound intracellular inclusions. Diverse stressors cause divergence from the normal chlamydial developmental cycle to an aberrant state called chlamydial persistence. Persistence can be induced by host-specific factors such as intracellular nutrient deprivation or cytokine exposure, and exogenous factors such as beta-lactam exposure, which disrupts RB to EB conversion. Persistent chlamydiae are atypical in appearance and, as such, are called aberrant bodies (ABs), but remain viable. The primary hallmark of persistence is reversibility of this temporary non-infectious state; upon removal of the stressor, persistent chlamydiae re-enter normal development, and production of infectious EBs resumes. The beta-lactam amoxicillin (AMX) has been shown to induce chlamydial persistence in a murine vaginal infection model, using the mouse pathogenC. muridarum(CM) to model human CT infection. This remains, to date, the sole experimentally tractablein vivomodel of chlamydial persistence. Recently, we found that penicillinase-producing NG (PPNG) can alleviate AMX-induced CT and CM persistencein vitro.We hypothesized that PPNG vaginal co-infection would also alleviate AMX-induced CM persistence in mice. To evaluate this hypothesis, we modified the CM/AMX persistence mouse model, incorporating CM/PPNG co-infection. Contradicting our hypothesis, and recentin vitrofindings, PPNG vaginal co-infection failed to alleviate AMX-induced CM persistence.