bluuebunny/crossref_metadata_2025_split huggingface dataset:
Summary of the Fourth Annual American Sexually Transmitted Diseases Association Workshop on Improving Sexually Transmitted Infection Control Efforts Through Cross-Sector Collaboration
Authors: Van Gerwen Olivia , Griner Stacey , Davis Alissa , Footman Alison , Pinto Casey N. , Melendez Johan H. , Tuddenham Susan , Exten Cara , Soge Olusegun O. , Chakraborty Payal , Nenninger Ashley , Marlowe Elizabeth M. , Joseph Ajith M. , McGowin Chris L. , Seña Arlene C. , Fortenberry J. Dennis , Ghanem Khalil G. , Van Der Pol Barbara 
Published: May 2022

Abstract
The American Sexually Transmitted Diseases Association has, for several years, been conducting a cross-sector workshop to bring together a variety of stakeholders to develop ideas for collaboratively improving the sexually transmitted infection control efforts in the United States. In this summary, we share the content of discussions and ideas of the fourth annual workshop for future research and potential changes to practice with a focus on diagnostic capacity.
Long-term HIV treatment outcomes and associated factors in sub-Saharan Africa: multi-country longitudinal cohort analysis
Authors: Inzaule Seth C. , Kroeze Stefanie , Kityo Cissy M. , Siwale Margaret , Akanmu Sulaimon , Wellington Maureen , de Jager Marleen , Ive Prudence , Mandaliya Kishor , Stevens Wendy , Steegen Kim , Nankya Immaculate , Boender T. Sonia , Ondoa Pascale , Sigaloff Kim C.E. , de Wit Tobias F. Rinke , Hamers Raph L. 
Published: May 2022

Objective:
In a multicountry prospective cohort of persons with HIV from six countries between 2007 and 2015, we evaluated long-term outcomes of first-line non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy (ART), and risk factors for loss-to-follow-up, mortality, virological failure, and incomplete CD4+ T-cell recovery.

Methods:
We calculated cumulative incidence of lost-to-follow-up, death, virological failure (VL ≥ 1000 cps/ml) and incomplete CD4+ T-cell recovery (<500 cells/μl) at successive years, using Kaplan–Meier and Cox regression.

Results:
Of 2735 participants, 58.0% were female, median age was 37 (interquartile range [IQR] 32–43) years, and median pre-ART CD4+ T-cell count was 135 (IQR 63–205)/μl. Total follow-up time was 7208 person-years (median 24.3 months, IQR 18.7–58.3). Deaths by any cause and loss to follow-up occurred mostly during the first year of ART (84%, 201/240 and 56%, 199/353, respectively). During their first 6 years of ART, 71% (95% confidence interval [CI] 69.0–73.7) were retained on first-line, and among those 90–93% sustained viral suppression (<1000 cps/ml); CD4+ T-cell recovery was incomplete in 60% (220/363) of participants. The risk factors associated with poor outcomes during long-term ART were: for loss-to-follow-up, recent VL ≥1000 cps/ml, recent CD4+ T-cell count ≤50 cells/μl, age <30 years, being underweight; for mortality, recent CD4+ T-cell count ≤50 cells/μl; and, for virological failure, age <40 years, recent CD4+ T-cell count ≤200 cells/μl, poor adherence, male sex, and low-level viremia.

Conclusion:
To achieve long-term ART success towards the UNAIDS targets, early ART initiation is crucial, coupled with careful monitoring and retention support, particularly in the first year of ART. Male and youth-centred care delivery models are needed to improve outcomes for those vulnerable groups.
Incidence of Glomerulonephritis after SARS-CoV-2 mRNA Vaccination
Authors: Diebold Matthias , Locher Eleonore , Boide Philipp , Enzler-Tschudy Annette , Faivre Anna , Fischer Ingeborg , Helmchen Birgit , Hopfer Helmut , Kim Min Jeong , Moll Solange , Nanchen Giliane , Rotman Samuel , Saganas Charalampos , Seeger Harald , Kistler Andreas D. 
Published: May 2022

AbstractNumerous cases of glomerulonephritis manifesting shortly after SARS-CoV-2 vaccination have been reported, but causality remains unproven. We studied the association between mRNA-based SARS-CoV-2 vaccination and new-onset glomerulonephritis using a nationwide retrospective cohort and case-cohort design. Data from all Swiss pathology institutes processing native kidney biopsies served to calculate incidence of IgA nephropathy, pauci-immune necrotizing glomerulonephritis, minimal change disease and membranous nephropathy. The observed incidence during the vaccination campaign (Jan to Aug 2021) was not different from the expected incidence based on the years 2015 to 2019 (incidence rate ratio 0.86, 95%-credible interval 0.73–1.02) and did not cross the upper boundary of the 95% credible interval for any month. Among 111 patients aged >18 years with newly diagnosed glomerulonephritis between January and August 2021, 38.7% had received at least one vaccine dose before biopsy, compared to 39.5% of the general Swiss population matched for age and calendar-time. The estimated risk ratio for the development of new-onset biopsy-proven glomerulonephritis was 0.97 (95% CI 0.66–1.42, P=0.95) in vaccinated vs. unvaccinated individuals. Patients with glomerulonephritis manifesting within 4 weeks after vaccine did not differ clinically from the rest of the cohort. Results were consistent across all types of glomerulonephritis with the possible exception of minimal change disease. In conclusion, vaccination against SARS-CoV-2 was not associated with new-onset glomerulonephritis in these two complementary studies. Most temporal associations between SARS-CoV-2 vaccination and glomerulonephritis are likely coincidental.
Somatic copy number variant load in neurons of healthy controls and Alzheimer’s disease patients
Authors: Turan Zeliha Gözde , Richter Vincent , Bochmann Jana , Parvizi Poorya , Yapar Etka , Işıldak Ulaş , Waterholter Sarah-Kristin , Leclere-Turbant Sabrina , Son Çağdaş Devrim , Duyckaerts Charles , Yet İdil , Arendt Thomas , Somel Mehmet , Ueberham Uwe 
Published: May 2022

BackgroundThe possible role of somatic copy number variations (CNVs) in Alzheimer’s disease (AD) aetiology has been controversial. Although cytogenetic studies suggested increased CNV loads in AD brains, a recent single-cell whole-genome sequencing (scWGS) experiment, studying frontal cortex brain samples, found no such evidence. Here we readdressed this issue using lowcoverage scWGS on pyramidal neurons dissected using laser capture microdissection (LCM) across five brain regions: entorhinal cortex, temporal cortex, hippocampal CA1, hippocampal CA3, and the cerebellum.ResultsAmong reliably detected somatic CNVs identified in 1301 cells obtained from the brains of 13 AD patients and 7 healthy controls, deletions were more frequent compared to duplications. Interestingly, we observed slightly higher frequencies of CNV events in cells from AD compared to similar numbers of cells from controls (4.1% vs. 1.4%, or 0.9% vs. 0.7%, using different filtering approaches), although the differences were not statistically significant. We also observed that LCM-isolated cells show higher within-cell read depth variation compared to cells isolated with fluorescence activated cell sorting (FACS), which we argue may have both biological and technical causes. Furthermore, we found that LCM-isolated neurons in AD harbour slightly more read depth variability than neurons of controls, which might be related to the reported hyperploid profiles of some AD-affected neurons. We also propose a principal component analysis-based denoising approach that significantly reduces within-cell read depth variation in scWGS data.ConclusionsWe find slightly higher somatic CNV frequencies in the brains of AD patients, and higher sequencing coverage variability, although the effects measured do not reach statistical significance. The results call for improved experimental protocols to determine the possible role of CNVs in AD pathogenesis.
Incilius alvarius cell-based synthesis of 5-MeO-DMT
Authors: Lerer Leonard , Reynolds Eric , Varia Jeet , Blakolmer Karin , Lerer Bernard 
Published: May 2022

AbstractThere is growing interest in the therapeutic potential of 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) for psychiatric disorders. While 5-MeO-DMT can be chemically synthesized, the parotoid gland secretions of Incilius alvarius (also known as the Colorado River or Sonoran Desert toad) contain 5-MeO-DMT and other molecules including bufotenine, bufagenins, bufotoxins, and indole alkylamines that may have individual clinical utility or act as entourage molecules to enhance the activity of 5-MeO-DMT. Incilius alvarius is currently under severe ecological pressure due to demand for natural 5-MeO-DMT and habitat loss. We established a cell line from tissue obtained by wedge biopsy of the Incilius alvarius parotoid gland and confirmed the cell-based biosynthesis of 5-MeO-DMT by LC-MS/MS. Cell-based biosynthesis of Incilius alvarius parotoid gland secretions is a potentially cruelty-free and sustainable source of naturally derived 5-MeO-DMT for research and drug development.Graphical Abstract
Unique Effects of Sedatives, Dissociatives, Psychedelics, Stimulants, and Cannabinoids on Episodic Memory: A Review and Reanalysis of Acute Drug Effects on Recollection, Familiarity, and Metamemory
Authors: Doss Manoj K. , Samaha Jason , Barrett Frederick S. , Griffiths Roland R. , de Wit Harriet , Gallo David A. , Koen Joshua D. 
Published: May 2022

AbstractDespite distinct classes of psychoactive drugs producing putatively unique states of consciousness, there is surprising overlap in terms of their effects on episodic memory and cognition more generally. Episodic memory is supported by multiple subprocesses that have been mostly overlooked in psychopharmacology and could differentiate drug classes. Here, we reanalyzed episodic memory confidence data from 10 previously published datasets (28 drug conditions total) using signal detection models to estimate 2 conscious states involved in episodic memory and 1 consciously-controlled metacognitive process of memory: the retrieval of specific details from one’s past (recollection), noetic recognition in the absence of retrieved details (familiarity), and accurate introspection of memory decisions (metamemory). We observed that sedatives, dissociatives, psychedelics, stimulants, and cannabinoids had unique patterns of effects on these mnemonic processes dependent on which phase of memory (encoding, consolidation, or retrieval) was targeted. All drugs at encoding except stimulants impaired recollection, and sedatives, dissociatives, and cannabinoids at encoding impaired familiarity. The effects of sedatives on metamemory were mixed, whereas dissociatives and cannabinoids at encoding tended to enhance metamemory. Surprisingly, psychedelics at encoding tended to enhance familiarity and did not impact metamemory. Stimulants at encoding and retrieval enhanced metamemory, but at consolidation, they impaired metamemory. Together, these findings may have relevance to mechanisms underlying unique subjective phenomena under different drug classes, such as blackouts from sedatives or déjà vu from psychedelics. This study provides a framework for interrogating drug effects within a domain of cognition beyond the global impairments on task performance typically reported in psychopharmacology.Public significance statementThis systematic review and reanalysis of several datasets indicate that sedatives (alcohol, zolpidem, triazolam), dissociatives (ketamine, dextromethorphan), psychedelics (psilocybin, MDMA), stimulants (dextroamphetamine, dextromethamphetamine), and cannabinoids (THC) can each have idiosyncratic effects on episodic memory, differentially impairing certain mnemonic processes while sparing or even facilitating others. Such findings inform how different drugs can produce unique subjective phenomena and provide a framework for future work to differentiate the effects of psychoactive drugs within a domain of cognition.
Variant-specific symptoms of COVID-19 among 1,542,510 people in England
Authors: Whitaker Matthew , Elliott Joshua , Bodinier Barbara , Barclay Wendy , Ward Helen , Cooke Graham , Donnelly Christl A. , Chadeau-Hyam Marc , Elliott Paul 
Published: May 2022

AbstractInfection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study has been monitoring the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell and taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and induced changes in daily activities will become increasingly important.
The SARS-CoV-2 spike protein binds and modulates estrogen receptors
Authors: Solis Oscar , Beccari Andrea R. , Iaconis Daniela , Talarico Carmine , Ruiz-Bedoya Camilo A. , Nwachukwu Jerome C. , Cimini Annamaria , Castelli Vanessa , Bertini Riccardo , Montopoli Monica , Cocetta Veronica , Borocci Stefano , Prandi Ingrid G. , Flavahan Kelly , Bahr Melissa , Napiorkowski Anna , Chillemi Giovanni , Ooka Masato , Yang Xiaoping , Zhang Shiliang , Xia Menghang , Zheng Wei , Bonaventura Jordi , Pomper Martin G. , Hooper Jody E. , Morales Marisela , Rosenberg Avi Z. , Nettles Kendall W. , Jain Sanjay K. , Allegretti Marcello , Michaelides Michael 
Published: May 2022

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 (ACE2) at the cell surface, which constitutes the primary mechanism driving SARS-CoV-2 infection. Molecular interactions between the transduced S and endogenous proteins likely occur post-infection, but such interactions are not well understood. We used an unbiased primary screen to profile the binding of full-length S against >9,000 human proteins and found significant S-host protein interactions, including one between S and human estrogen receptor alpha (ERα). After confirming this interaction in a secondary assay, we used bioinformatics, supercomputing, and experimental assays to identify a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 subunit and an S-ERα binding mode. In cultured cells, S DNA transfection increased ERα cytoplasmic accumulation, and S treatment induced ER-dependent biological effects and ACE2 expression. Noninvasive multimodal PET/CT imaging in SARS-CoV-2-infected hamsters using [18F]fluoroestradiol (FES) localized lung pathology with increased ERα lung levels. Postmortem experiments in lung tissues from SARS-CoV-2-infected hamsters and humans confirmed an increase in cytoplasmic ERα expression and its colocalization with S protein in alveolar macrophages. These findings describe the discovery and characterization of a novel S-ERα interaction, imply a role for S as an NRC, and are poised to advance knowledge of SARS-CoV-2 biology, COVID-19 pathology, and mechanisms of sex differences in the pathology of infectious disease.
Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine candidate is protective in macaques
Authors: Le Nouën Cyril , Nelson Christine E. , Liu Xueqiao , Park Hong-Su , Matsuoka Yumiko , Luongo Cindy , Santos Celia , Yang Lijuan , Herbert Richard , Castens Ashley , Moore Ian N. , Wilder-Kofie Temeri , Moore Rashida , Walker April , Zhang Peng , Lusso Paolo , Johnson Reed F. , Garza Nicole L. , Via Laura E. , Munir Shirin , Barber Daniel , Buchholz Ursula J. 
Published: May 2022

SUMMARYPediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways, as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal IgA and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4+ and CD8+ T-cell responses, including tissue-resident memory cells in lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine.One-Sentence SummaryIntranasal parainfluenza virus-vectored COVID-19 vaccine induces anti-S antibodies, T-cell memory and protection in macaques.
Non-equilibrium protein folding and activation by ATP-driven chaperones
Authors: Xu Huafeng 
Published: May 2022

AbstractRecent experimental studies suggest that ATP-driven molecular chaperones can stabilize protein sub-strates in their native structures out of thermal equilibrium. The mechanism of such non-equilibrium protein folding is an open question. Based on available structural and biochemical evidence, I propose here a unifying principle that underlies the conversion of chemical energy from ATP hydrolysis to the conformational free energy associated with protein folding and activation. I demonstrate that non-equilibrium folding requires the chaperones to break at least one of four symmetry conditions. The Hsp70 and Hsp90 chaperones each breaks a different subset of these symmetries and thus they use different mechanisms for non-equilibrium protein folding. I derive an upper bound on the non-equilibrium elevation of the native concentration, which implies that non-equilibrium folding only occurs in slow-folding proteins that adopt an unstable intermediate conformation in binding to ATP-driven chaperones. Contrary to the long-held view of Anfinsen’s hypothesis that proteins fold to their conformational free energy minima, my results predict that some proteins may fold into thermo-dynamically unstable native structures with the assistance of ATP-driven chaperones, and that the native structures of some chaperone-dependent proteins may be shaped by their chaperone-mediated folding pathways.
Enhancing the anti-tumor efficacy of Bispecific T cell engagers via cell surface glycocalyx editing
Authors: Yang Zhuo , Hou Yingqin , Grande Geramie , Wang Chao , Shi Yujie , Zak Jaroslav , Cho Jong Hyun , Liu Dongfang , Teijaro John R. , Lerner Richard A. , Wu Peng 
Published: May 2022

AbstractBispecific T-cell engager (BiTE)-based cancer therapies that activate the cytotoxic T cells of a patient’s own immune system have gained momentum with the recent FDA approval of Blinatumomab for treating B cell malignancies. However, this approach has had limited success in targeting solid tumors. Here, we report the development of BiTE-sialidase fusion proteins that enhance tumor cell susceptibility to BiTE-mediated cytolysis by T cells via targeted desialylation at the BiTE-induced T cell-tumor cell interface. Targeted desialylation results in better immunological synapse formation, T-cell activation and effector function. As a result, BiTE-sialidase fusion proteins show remarkably increased efficacy in inducing T-cell-dependent tumor cell cytolysis in response to target antigens compared to the parent BiTE molecules alone. This enhanced function is seen bothin vitroand inin vivoxenograft and syngeneic solid tumor mouse models. Our findings highlight BiTE-sialidase fusion proteins as promising candidates for the development of next-generation bispecific T-cell engaging molecules for cancer immunotherapy.
Estimating chromosome sizes from karyotype images enables validation of de novo assemblies
Authors: Ludwig Arne , Dibrov Alexandr , Myers Gene , Pippel Martin 
Published: May 2022

AbstractHighly contiguous genome assemblies are essential for genomic research. Chromosome-scale assembly is feasible with the modern sequencing techniques in principle, but in practice, scaffolding errors frequently occur, leading to incorrect number and sizes of chromosomes. Relating the observed chromosome sizes from karyotype images to the generated assembly scaffolds offers a method for detecting these errors.Here, we present KICS, a semi-automated approach for estimating relative chromosome sizes from karyotype images and their subsequent comparison to the corresponding assembly scaffolds. The method relies on threshold-based image segmentation and uses the computed areas of the chromosome-related connected components as a proxy for the actual chromosome size. We demonstrate the validity and practicality of our approach by applying it to karyotype images of humans and various amphibians, birds, fish, insects, mammals, and plants. We found a strong linear relationship between pixel counts and the DNA content of chromosomes. Averaging estimates from eight human karyotype images, KICS predicts most of the chromosome sizes within an error margin of just 6 Mb.Our method provides additional means of validating genome assemblies at low costs. An interactive implementation of KICS is available at https://github.com/mpicbg-csbd/napari-kics.
Greater alteration of gut microbiota occurs in childhood obesity than adulthood obesity
Authors: Yu Zhongjia , Yu Xiang-Fang , Zhao Xiu , Ren Pei-Gen 
Published: May 2022

AbstractThe children’s gut microbiota, associated with the development of obesity, is in maturation. The impact of obesity on the gut microbiota in childhood could have a more significant effect than on adulthood and eventually be lifelong lasting, but it has been rarely studied. Aimed to discover the difference in gut microbiota between obese children and adults, we collected and re-analyzed published data from National Center for Biotechnology Information (NCBI). We found that the gut microbiota had a significant difference between children with and without obesity, but this did not happen in adults. Based on the random forest model, childhood obesity is more challenging to predict using gut microbiota than adulthood obesity. Our results suggest that gut microbiota in childhood is more easily affected than in adulthood. Hence, early intervention for childhood obesity is essential to improve children’s health and lifelong gut microbiota-related health.
Turing Test Inspired Method for Analysis of Biases Prevalent in Artificial Intelligence-Based Medical Imaging
Authors: Tripathi Satvik , Augustin Alisha Isabelle , Dako Farouk , Kim Edward 
Published: May 2022

AbstractBackgroundBecause of the growing need to provide better global healthcare, computer-based and robotic healthcare equipment that depend on artificial intelligence have seen an increase in development. In order to evaluate artificial intelligence (AI) in computer technology, the Turing test was created. For evaluating the future generation of medical diagnostics and medical robots, it remains an essential qualitative instrument.MethodWe propose a novel methodology to assess AI-based healthcare technology that provided verifiable diagnostic accuracy and statistical robustness. In order to run our test, we used a State-of-the-art AI model and compared it against radiologist for checking how generalized of the model is and if any biases are prevalent.ResultsWe achieved results that can evaluate the performance of our chosen model for this study in a clinical setting and we also applied a quantifiable methods for evaluating our modified turing test results using a meta-analytical evaluation framework.ConclusionThis test provides a translational standard for upcoming AI modalities. Our modified Turing Test is a notably strong standard to measure the actual performance of the AI model on a variety of edge cases and normal cases and also helps in detecting if the algorithm is biased towards any one type of case. This method extends the flexibility detect any prevalent biases and also classify the type of bias.