bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delivering HIV pre-exposure prophylaxis (PrEP) care online: A scoping review
Authors: Kincaid Ross , Estcourt Claudia , Frankis Jamie , Dalrymple Jenny , Gibbs Jo 
Published: December 2021

ABSTRACTObjectivesHIV pre-exposure prophylaxis (PrEP), in which people take HIV medication to prevent HIV acquisition, is a highly effective method of HIV prevention; however, global implementation of PrEP is patchy. PrEP provision will need to be upscaled significantly to achieve UNAIDS/WHO goals of elimination of HIV transmission. Online provision of PrEP care could enhance access to, and delivery of, care at scale. We explored the extent to which PrEP care has been delivered online to inform the development of a novel online PrEP clinic.DesignScoping review.Data sourcesEmbase, MEDLINE, Web of Science, CINAHL, PsycINFO, ASSIA, PUBMED, Open Grey, and EThOS databases.Eligibility criteriaEnglish language articles describing a service that delivered one or more element of PrEP-related care online, published from 2009 onwards.Data extraction and synthesisData were extracted using matrices and synthesised using summary statistics and thematic analysis. The Mixed Methods Appraisal Tool was used to assess study quality.ResultsFifty-nine articles were included: eight randomised controlled trials, 12 non-randomised quantitative studies, 30 descriptive quantitative studies, 14 qualitative studies, and four reviews of online content. Seven studies detailed comprehensive PrEP care pathways that used a combination of online, face-to-face and telephone based care. Of the remaining studies, the majority focused on HIV testing outside a PrEP context. Care tended to be delivered via websites (n=41), video chat, and smartphone apps (both n=10). The acceptability and feasibility of delivering elements of care online was high.ConclusionsOnline PrEP care appears feasible and acceptable, offering convenience and a means to overcome some of the reported barriers to face-to-face care. Services tended to focus on a single element of PrEP-related care or use a combination of online, face-to-face and phone-based care. Additional formative work is needed to inform the development of complete online PrEP care pathways.Strengths and limitations of this studyThis scoping review provides a comprehensive, critical overview of existing literature related to online provision of HIV pre-exposure prophylaxis (PrEP)-related care.We developed a comprehensive definition of PrEP care which took into consideration all essential elements of care required for safe and appropriate PrEP prescribing.Established guidelines for conducting and reporting scoping reviews were followed throughout.We conducted an exhaustive search of nine databases.The heterogeneity in design and aim of the included studies limited our ability to synthesise findings.
COVID-19 and Indian population: a comparative genetic analysis
Authors: Patil Saurabh , Pemmasani Sandhya Kiran , Chitturi Neelima , Bhatnagar Ishita , Acharya Anuradha , Subash Lingareddy Venkata 
Published: December 2021

ABSTRACTBackgroundMajor risk factors of COVID-19 include older age, male gender, and comorbidities. In addition, host genetic makeup is also known to play a major role in COVID-19 susceptibility and severity. To assess the genetic predisposition of the Indian population to COVID-19, a comparative analysis of the frequencies of polymorphisms directly or potentially associated with COVID-19 susceptibility, severity, immune response, and fatal outcomes was done between the Indian population and other major populations (European, African, East Asian, South Asian, and American).Materials and methodsPolymorphisms directly or potentially associated with COVID-19 susceptibility, severity, immune response, and mortality were mined from genetic association studies, comparative genetic studies, expression quantitative trait loci studies among others. Genotype data of these polymorphisms were either sourced from the GenomegaDB™ database of Mapmygenome India Ltd. (sample size = 3054; Indian origin) or were imputed. Polymorphisms with minor allele frequency >= 0.05 and that are in Hardy-Weinberg equilibrium in the Indian population were considered for allele frequency comparison between the Indian population and 1000 Genome population groups.ResultsAllele frequencies of 421 polymorphisms were found to be significantly different in the Indian population compared to European, African, East Asian, South Asian, and American populations. 128 polymorphisms were shortlisted based on linkage disequilibrium and were analyzed in detail. Apart from well-studied genes, like ACE2, TMPRSS2, ADAM17, and FURIN, variants from AHSG, IFITM3, PTPN2, CD209, CCL5, HEATR9, SELENBP9, AGO1, HLA-G, MX1, ICAM3, MUC5B, CRP, C1GALT1, and other genes were also found to be significantly different in Indian population. These variants might be implicated in COVID-19 susceptibility and progression.ConclusionOur comparative study unraveled multiple genetic variants whose allele frequencies were significantly different in the Indian population and might have a potential role in COVID-19 susceptibility, its severity, and fatal outcomes. This study can be very useful for selecting candidate genes/variants for future COVID-19 related genetic association studies.
Comparison of the Immunogenicity of five COVID-19 vaccines in Sri Lanka
Authors: Jeewandara Chandima , Aberathna Inoka Sepali , Danasekara Saubhagya , Gomes Laksiri , Fernando Suranga , Guruge Dinuka , Ranasinghe Thushali , Gunasekera Banuri , Kamaladasa Achala , Kuruppu Heshan , Somathilake Gayasha , Jayamali Jeewantha , Jayathilaka Deshni , Wijayatilake Helanka Dinesh Kumara , Pushpakumara Pradeep Darshana , Harvie Michael , Nimasha Thashmi , de Silva Shiromi Devika Grace , Wijayamuni Ruwan , Schimanski Lisa , Rijal Pramila , Tan Jack , Townsend Alain , Ogg Graham S. , Malavige Gathsaurie Neelika 
Published: December 2021

AbstractWe assessed antibody responses 3 months post-vaccination in those who received mRNA-1273 (n=225), Sputnik V (n=128) or the first dose of Gam-COVID-Vac (n=184) and compared the results with previously reported data of Sinopharm and AZD1222 vaccinees. 99.5% of Moderna >94% of AZD1222 or Sputnik V, 72% to 76% of Gam-COVID-Vac (first dose) and 38.1% to 68.3% of Sinopharm vaccinees had ACE2 blocking antibodies above the positive threshold. The ACE2 blocking antibody levels were highest to lowest was Moderna > Sputnik V/ AZD1222 (had equal levels)> first dose of Gam-COVID-Vac > Sinopharm. All Moderna recipients had antibodies above the positive threshold to the ancestral (WT), B.1.1.7, B.1.351.1 and 80% positivity rate for B.1.617.2. Positivity rates of Sputnik V vaccinees for WT and variants, were higher than AZD1222 vaccinees, while Sinopharm vaccinees had the lowest positivity rates (<16.7%). These findings highlight the need for further studies to understand the effects on clinical outcomes.
A combined transcriptional and dynamic roadmap of single human pancreatic endocrine progenitors reveals proliferative capacity and differentiation continuum
Authors: Beydag-Tasöz Belin Selcen , D’Costa Joyson Verner , Hersemann Lena , Luppino Federica , Kim Yung Hae , Zechner Christoph , Grapin-Botton Anne 
Published: December 2021

SummaryBasic helix-loop-helix genes, particularly proneural genes, are well-described triggers of cell differentiation, yet limited information exists on their dynamics, notably in human development. Here, we focus on Neurogenin 3 (NEUROG3), which is crucial for pancreatic endocrine lineage initiation. Using a double reporter to monitor endogenous NEUROG3 transcription and protein expression in single cells in 2D and 3D models of human pancreas development, we show peaks of expression for the RNA and protein at 22 and 11 hours respectively, approximately two-fold slower than in mice, and remarkable heterogeneity in peak expression levels all triggering differentiation. We also reveal that some human endocrine progenitors proliferate once, mainly at the onset of differentiation, rather than forming a subpopulation with sustained proliferation. Using reporter index-sorted single-cell RNA-seq data, we statistically map transcriptome to dynamic behaviors of cells in live imaging and uncover transcriptional states associated with variations in motility as NEUROG3 levels change, a method applicable to other contexts.
Can associative learning be the general process for intelligent behavior in non-human animals?
Authors: Lind Johan , Vinken Vera 
Published: December 2021

AbstractThe general process- and adaptive specialization hypotheses represent two contrasting explanations for understanding intelligence in non-human animals. The general process hypothesis proposes that associative learning underlies all learning, whereas the adaptive specialization hypothesis suggests additional distinct learning processes required for intelligent behavior. Here, we use a selection of experimental paradigms commonly used in comparative cognition to explore these hypotheses. We tested if a novel computational model of associative learning — A-learning — could solve the problems presented in these tests. Results show that this formulation of associative learning suffices as a mechanism for general animal intelligence, without the need for adaptive specialization, as long as adequate motor- and perceptual systems are there to support learning. In one of the tests, however, the addition of a short-term trace memory was required for A-learning to solve that particular task. We further provide a case study showcasing the flexibility, and lack thereof, of associative learning, when looking into potential learning of self-control and the development of behavior sequences. From these simulations we conclude that the challenges do not so much involve the complexity of a learning mechanism, but instead lie in the development of motor- and perceptual systems, and internal factors that motivate agents to explore environments with some precision, characteristics of animals that have been fine-tuned by evolution for million of years.Author summaryWhat causes animal intelligence? One hypothesis is that, among vertebrates, intelligence relies upon the same general processes for both memory and learning. A contrasting hypothesis states that important aspects of animal intelligence come from species- and problem specific cognitive adaptations. Here, we use a recently formulated model of associative learning and subject it, through computer simulations, to a battery of tests designed to probe cognitive abilities in animals. Our computer simulations show that this associative learning model can account well for how animals learn these various tasks. We conclude that a major challenge in understanding animal and machine intelligence lies in describing behavior systems. Specifically, how motor flexibility and perceptual systems together with internal factors allow animals and machines to navigate the world. As a consequence of our results, together with current progress in both animal- and machine learning, we cannot reject the idea that associative learning provides a general process for animal intelligence.
METTL3 facilitates hepatic fibrosis progression via m6A-YTHDF2 dependent silencing of GPR161
Authors: Pan Xue-yin , Bi Yi-hui , Cheng Miao , Qian Zhen-zhen , Wang Ling , You Hong-mei , Liu Lei , Zhang Zhen-hua , Meng Xiao-ming , Huang Cheng , Li Jun 
Published: December 2021

AbstractHepatic fibrosis (HF) is a very common condition seen in millions of patients with various liver diseases. N6-methyladenosine (m6A) plays critical roles in various biological and pathological processes. However, the role of m6A and its main methyltransferase METTL3 in HF remains obscure. Here, we reported that METTL3 expression was elevated in HSCs from CCl4 induced fibrotic liver. METTL3 knockdown in HSCs mediated by recombinant adeno-associated-virus serotype 9 packed short hairpin RNA against METTL3 alleviated liver injury and fibrosis compared to empty carrier group. Mechanistically, the decreased liver fibrosis in CCl4-treated HSC-specific METTL3 knockdown mice was due to the increased GPR161 that is a suppressor of Hedgehog pathway, a well-known pathway to activate in liver injury and regeneration. As expect, GPR161 transferred into HSCs alleviated liver fibrosis and HSC activation. Forced GPR161 expression inhibited Gli3 activated form nuclear accumulation and subsequently suppressed fibrosis-associate gene expression. Conclusion, HSC-specific deletion of METTL3 inhibits liver fibrosis via elevated GPR161 expression, which subsequently suppressed Hedgehog pathway activation and fibrosis-associated genes expression, providing novel therapeutic targets for HF therapy.SynopsisThe role of RNA m6A methyltransferase METTL3 in the progression of hepatic fibrosis is unclear. Here, we reveal that suppresses m6A modification by depletion of METTL3 in Hepatic Stellate Cells (HSCs), stabilizes the GPR161 transcripts, that involved in suppressing Hedgehog signaling pathway, through YTHDF2, thereby alleviating the fibrosis feature of CCl4-induced liver injury.Disruption of m6A methyltransferases METTL3 in HSCs alleviates liver fibrosis feature.METTL3 depletion in liver HSCs suppresses its activation by suppressing Hedgehog signaling pathway through stabilizing GPR161 transcripts in an m6A-YTHDF2 dependent manner.GPR161 activates PKA that mediates phosphorylation and degradation of full-length Gli3 (Gli3-FL) protein, then the short Gli3 (Gli3-R) translocated into the nucleus and suppresses the fibrosis associated gene transcription.The elevated METTL3 expression is attribute to its promoter H3K27ac modification.
Short senolytic or senostatic interventions rescue progression of radiation-induced frailty and premature ageing in mice
Authors: Fielder Edward , Wan Tengfei , Alimohammadiha Ghazaleh , Ishaq Abbas , Low Evon , Weigand B. Melanie , Kelly George , Parker Craig , Griffin Brigid , Jurk Diana , Korolchuk Viktor I. , von Zglinicki Thomas , Miwa Satomi 
Published: December 2021

AbstractCancer survivors suffer from progressive frailty, multimorbidity and premature morbidity. We hypothesize that therapy-induced senescence and senescence progression via bystander effects is a significant cause of this premature ageing phenotype. Accordingly, the study addresses the question whether a short anti-senescence intervention is able to block progression of radiation-induced frailty and disability in a pre-clinical setting.Male mice were sub-lethally irradiated at 5 months of age and treated (or not) with either a senolytic drug (Navitoclax or dasatinib + quercetin) for 10 days or with the senostatic metformin for 10 weeks. Follow up was for one year. Treatments commencing within a month after irradiation effectively reduced frailty progression (p<0.05) and improved muscle (p<0.01) and liver (p<0.05) function as well as short-term memory (p<0.05) until advanced age with no need for repeated interventions. Senolytic interventions that started late, after radiation-induced premature frailty was manifest, still had beneficial effects on frailty (p<0.05) and short-term memory (p<0.05). Metformin was similarly effective as senolytics. At therapeutically achievable concentrations metformin acted as a senostatic neither via inhibition of mitochondrial complex I, nor via improvement of mitophagy or mitochondrial function, but by reducing non-mitochondrial ROS production via NOX4 inhibition in senescent cells.Our study suggests that the progression of adverse long-term health and quality-of-life effects of radiation exposure, as experienced by cancer survivors, might be rescued by short-term adjuvant anti-senescence interventions.
Automated identification of chicken distress vocalisations using deep learning models
Authors: Mao Axiu , Giraudet Claire , Liu Kai , De Almeida Nolasco Inês , Xie Zhiqin , Xie Zhixun , Gao Yue , Theobald James , Bhatta Devaki , Stewart Rebecca , McElligott Alan G. 
Published: December 2021

AbstractThe annual global production of chickens exceeds 25 billion birds, and they are often housed in very large groups, numbering thousands. Distress calling triggered by various sources of stress has been suggested as an “iceberg indicator” of chicken welfare. However, to date, the identification of distress calls largely relies on manual annotations, which is very labour-intensive and time-consuming. Thus, a novel light-VGG11 was developed to automatically identify chicken distress calls using recordings (3,363 distress calls and 1,973 natural barn sounds) collected on intensive chicken farms. The light-VGG11 was modified from VGG11 with a significantly smaller size in parameters (9.3 million vs 128 million) and 55.88% faster detection speed while displaying comparable performance, i.e., precision (94.58%), recall (94.89%), F1-score (94.73%), and accuracy (95.07%), therefore more useful for model deployment in practice. To further improve the light-VGG11’s performance, we investigated the impacts of different data augmentation techniques (i.e., time masking, frequency masking, mixed spectrograms of the same class, and Gaussian noise) and found that they could improve distress calls detection by up to 1.52%. In terms of precision livestock farming, our research opens new opportunities for developing technologies used to monitor the output of distress calls in large, commercial chicken flocks.
mslp: a comprehensive pipeline in predicting cancer mutations specific synthetic lethal partners
Authors: Shao Chunxuan 
Published: December 2021

AbstractBackgroundMutation specific synthetic lethal partners (SLPs) offer significant insights in identifying novel targets and designing personalized treatments in cancer studies. Large scale genetic screens in cell lines and model organisms provide crucial resources for mining SLPs, yet those experiments are expensive and might be difficult to set up. Various computational methods have been proposed to predict the potential SLPs from different perspectives. However, those efforts are hampered by the low signal-to-noise ratio in simple correlation based approaches, or incomplete reliable training sets in supervised approaches.ResultsHere we present mslp, a comprehensive pipeline to identify potential SLPs via integrating genomic and transcriptomic datasets from both patient tumours and cancer cell lines. Leveraging cuttingedges algorithms, we identify a broad spectrum of primary SLPs for mutations presented in patient tumours. Further, for mutations detected in cell lines, we develop the idea of consensus SLPs which are also identified as screen hits, and show consistency impact on cell viability. Applied in real datasets, we successfully identified known synthetic lethal gene pairs. Remarkably, genetic screen results suggested that consensus SLPs have a significant impact on cell viability compared to common hits.ConclusionsMslp is a powerful and flexible pipeline to identify potential SLPs in a cancer context-specific manner, which might aid in drug developments and precise medicines in cancer treatments. The pipeline is implemented in R and freely available in github.
Reciprocity between retrograde signal and putative metalloprotease reconfigures plastidial metabolism and structure
Authors: Wang Jin-Zheng , van de Ven Wilhelmina , Xiao Yanmei , He Xiang , Ke Haiyan , Yang Panyu , Dehesh Katayoon 
Published: December 2021

AbstractReconfiguration of the plastidial proteome in response to environmental inputs is central to readjustment of its metabolic and structural states. This is necessary for the functionality of this metabolic hub, and the maintenance of organismal integrity. This report establishes the role of the plastidial retrograde signaling metabolite, MEcPP, in increasing the abundance of the putative plastidial metalloprotease (VIR3), and the ensuing decline of VIR3 target enzymes, ascorbate peroxidase and glyceraldehyde 3-phophate dehydrogenase B. The decreased abundance of these enzymes is linked to increased levels of their substrates: H2O2, an elicitor of salicylic acid production and stromule formation; and G3P the substrate for MEcPP synthesis. High-light treatment of wild type plants recapitulated the VIR3-associated reconfiguration of the plastidial metabolic and structural states. These results identify a previously unrecognized link between the stress-induced plastidial retrograde signaling metabolite and a putative zinc-binding metalloprotease. Moreover, the data reveal that the reciprocity between these two components, results in the reconfiguration of the metabolic and structural states of the plastid, deemed necessary to maintain cellular integrity and to shape adaptive responses.
Leptomeningeal Enhancement in Multiple Sclerosis and Other Neurological Diseases: A Systematic Review and Meta-Analysis
Authors: Ineichen Benjamin V. , Tsagkas Charidimos , Absinta Martina , Reich Daniel S. 
Published: December 2021

AbstractBackgroundThe lack of systematic evidence on leptomeningeal enhancement (LME) on MRI in neurological diseases, including multiple sclerosis (MS), hampers its interpretation in clinical routine and research settings.PurposeTo perform a systematic review and meta-analysis of MRI LME in MS and other neurological diseases.Materials and MethodsIn a comprehensive literature search in Medline, Scopus, and Embase, out of 2292 publications, 459 records assessing LME in neurological diseases were eligible for qualitative synthesis. Of these, 135 were included in a random-effects model meta-analysis with subgroup analyses for MS.ResultsOf eligible publications, 161 investigated LME in neoplastic neurological (n=2392), 91 in neuroinfectious (n=1890), and 75 in primary neuroinflammatory diseases (n=4038). The LME-proportions for these disease classes were 0.47 [95%-CI: 0.37–0.57], 0.59 [95%-CI: 0.47–0.69], and 0.26 [95%-CI: 0.20–0.35], respectively. In a subgroup analysis comprising 1605 MS cases, LME proportion was 0.30 [95%-CI 0.21–0.42] with lower proportions in relapsing-remitting (0.19 [95%-CI 0.13–0.27]) compared to progressive MS (0.39 [95%-CI 0.30–0.49], p=0.002) and higher proportions in studies imaging at 7T (0.79 [95%-CI 0.64–0.89]) compared to lower field strengths (0.21 [95%-CI 0.15–0.29], p<0.001). LME in MS was associated with longer disease duration (mean difference 2.2 years [95%-CI 0.2–4.2], p=0.03), higher Expanded Disability Status Scale (mean difference 0.6 points [95%-CI 0.2–1.0], p=0.006), higher T1 (mean difference 1.6ml [95%-CI 0.1–3.0], p=0.04) and T2 lesion load (mean difference 5.9ml [95%-CI 3.2–8.6], p<0.001), and lower cortical volume (mean difference −21.3ml [95%-CI −34.7–-7.9], p=0.002).ConclusionsOur study provides high-grade evidence for the substantial presence of LME in MS and a comprehensive panel of other neurological diseases. Our data could facilitate differential diagnosis of LME in clinical settings. Additionally, our meta-analysis corroborates that LME is associated with key clinical and imaging features of MS.PROSPERO No: CRD42021235026.Summary statementOur systematic review and meta-analysis synthesize leptomeningeal enhancement proportions across a comprehensive panel of neurological diseases, including multiple sclerosis, and assesses its prognostic value in multiple sclerosis.Summary dataLeptomeningeal enhancement (LME) is a nonspecific imaging feature present across many neurological disorders, including neoplasm, infection, and primary neuroinflammation.The presence of LME is associated with worse clinical and imaging outcomes in multiple sclerosis, justifying its ascertainment in clinical practice.Neuroinflammatory animal models can be used to further investigate the pathophysiology of LME, including its pathological tissue signature and/or its association with cortical pathology.