bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artificial Intelligence methods for Improved Detection of undiagnosed Heart Failure with Preserved Ejection Fraction (HFpEF)
Authors: Wu Jack , Biswas Dhruva , Ryan Matthew , Bernstein Brett , Rizvi Maleeha , Fairhurst Natalie , Kaye George , Baral Ranu , Searle Tom , Melikian Narbeh , Sado Daniel , Lüscher Thomas F , Grocott-Mason Richard , Carr-White Gerald , Teo James , Dobson Richard , Bromage Daniel I , McDonagh Theresa A , Shah Ajay M , O’Gallagher Kevin 
Published: September 2023

AbstractBackground and aimHeart Failure with preserved Ejection Fraction (HFpEF) remains under-diagnosed in clinical practice despite accounting for nearly half of all Heart Hailure (HF) cases. Accurate and timely diagnosis of HFpEF is crucial for proper patient management and treatment. In this study, we explored the potential of natural language processing (NLP) to improve the detection and diagnosis of HFpEF according to the European Society of Cardiology (ESC) diagnostic criteria.MethodsIn a retrospective cohort study, we used an NLP pipeline applied to the Electronic Health Record (EHR) to identify patients with a clinical diagnosis of HF between 2010-2022. We collected demographic, clinical, echocardiographic and outcome data from the EHR. Patients were categorised according to the left ventricular ejection fraction (LVEF). Those with LVEF ≥ 50% were further categorised based on whether they had a clinician-assigned diagnosis of HFpEF and if not, whether they met the ESC diagnostic criteria. Results were validated in a second, independent centre.ResultsWe identified 8606 patients with HF. Of 3727 consecutive patients with HF and LVEF ≥ 50% on echocardiogram, only 8.3% had a clinician-assigned diagnosis of HFpEF, while 75.4% met ESC criteria but did not have a formal diagnosis of HFpEF. Patients with confirmed HFpEF were hospitalised more frequently; however the ESC criteria group had a higher 5-year mortality, despite being less co-morbid and experiencing fewer acute cardiovascular events.ConclusionsThis study demonstrates that patients with undiagnosed HFpEF are an at-risk group with high mortality. It is possible to use NLP methods to identify likely HFpEF patients from EHR data who would likely then benefit from expert clinical review and complement the use of diagnostic algorithms.Graphical AbstractOf 3727 consecutive patients with a clinical diagnosis of HF and left ventricular ejection fraction (LVEF) >50% on echocardiogram, only 8.3% had a clinician-assigned diagnosis of HFpEF, while 75.4% met ESC criteria but did not have a formal diagnosis of HFpEF. The two groups had similar rates of hospitalisation however the ESC criteria group had a higher 5-year mortality.
Spinocerebellar ataxia type 2 has multiple ancestral origins
Authors: Sena Lucas Schenatto , Furtado Gabriel Vasata , Pedroso José Luiz , Barsottini Orlando , Cornejo-Olivas Mario , Nóbrega Paulo Ribeiro , Neto Pedro Braga , Soares Danyela Martins Bezerra , Vargas Fernando Regla , Godeiro Clecio , Medeiros Paula Frassinetti Vasconcelos de , Camejo Claudia , Toralles Maria Betania Pereira , Fagundes Nelson Jurandi Rosa , Jardim Laura Bannach , Saraiva-Pereira Maria Luiza 
Published: September 2023

AbstractSpinocerebellar ataxia type 2 (SCA2) is an adult onset, dominant neurodegenerative disorder due to expansions of a CAG repeat tract at theATXN2gene. A few studies on ancestral haplotypes were performed so far, and the allele C at rs695871 was always found in SCA2 carriers. We aimed to describe SCA2 ancestral haplotypes constructed based on the SNPs rs9300319, rs3809274, rs695871, rs1236900 and rs593226, using the STRs D12S1329, D12S1333, D12S1672 and D12S1332 to determine their genetic variation. Seventy-seven SCA2 families were recruited from Brazil, Peru, and Uruguay; 162 chromosomes from the Brazilian general population and the chromosomes with normal repeats from 101 SCA2 carriers were used as 263 controls. Eleven ancestral haplotypes were found in SCA2 families. The most frequent ones were A-G-C-C-C (46.7% of families), G-C-C-C-C (24.6%) and A-C-C-C-C (10.3%), with assigned risks of being associated with disease of δ = 0.326, 0.197 and 0, respectively. Their mean (sd) CAGexp were 41.68 (3.55), 40.42 (4.11) and 45.67 (9.70) (p= 0.055), while the mean (sd) CAG lengths at normal alleles were 23.85 (3.59), 22.97 (3.93) and 30.81 (4.27) (p< 0.001), respectively. The other SCA2 haplotypes were rare: among them, a G-C-G-A-T was found, evidencing a G allele in rs695871. In summary, our work identified eleven distinct SCA2 haplotypes in Brazilian, Uruguayan, and Peruvian families, including an unexpected SCA2 haplotype with a G allele at rs695871. These results suggest that SCA2 has multiple origins in these populations.
A PrEP Decision Aid for Women Survivors of Intimate Partner Violence: Task-Shifting Implementation to Domestic Violence Service Settings
Authors: Meyer Jaimie P. , Lazarus Elizabeth , Phillips Karlye , Watts Z. Thomasina , Duroseau Brenice , Carlson Cindy , Price Carolina R. , Kershaw Trace , Willie Tiara C. 
Published: September 2023

AbstractBackgroundWomen exposed to intimate partner violence (IPV) experience multiple social and structural barriers to accessing HIV pre-exposure prophylaxis (PrEP), despite being at increased risk for HIV. In addition, few existing HIV prevention interventions address IPV. A recently developed PrEP decision aid for women has the potential to reach IPV survivors at risk for HIV if it could be integrated into existing domestic violence agencies that prioritize trust and rapport with female IPV survivors. Leveraging non-traditional service delivery mechanisms in the community could expand reach to women who are IPV survivors for PrEP.MethodsWe conducted qualitative interviews and online qualitative surveys with 33 IPV survivors and 9 domestic violence agency staff at two agencies in Connecticut. We applied the Consolidated Framework for Implementation Research (CFIR) to understand barriers and facilitators to delivering a novel PrEP decision aid to IPV survivors in the context of domestic violence service agencies.ResultsMost IPV survivors and agency staff thought the PrEP decision aid intervention could be compatible with agencies’ existing practices, especially if adapted to be trauma-responsive and delivered by trusted counselors and staff members. PrEP conversations could be packaged into already well-developed safety planning and wellness practices. Agency staff noted some concerns about prioritizing urgent safety needs over longer-term preventive health needs during crisis periods and expressed interest in receiving further training on PrEP to provide resources for their clients.ConclusionsIPV survivors and agency staff identified key intervention characteristics of a PrEP decision aid and inner setting factors of the service agencies that are compatible. Any HIV prevention intervention in this setting would need to be adapted to be trauma-responsive and staff would need to be equipped with proper training to be successful.
Effectiveness of Online Training in Improving Primary Care Doctors’ Competency in Brief Tobacco Interventions: A Cluster Randomised Controlled Trial of WHO Modules in Delta State, Nigeria
Authors: Moeteke Nnamdi Stephen , Oyibo Patrick , Ochei Oboratare , Ntaji Maureen Iru , Awunor Nyemike Simeon , Adeyemi Mitchell Oritsewino , Enemuwe Ibobo Mike , Agbatutu Eseoghene , Adesoye Oluwaseun Opeyemi 
Published: September 2023

ABSTRACTBackgroundThe World Health Organisation (WHO) strongly recommends that brief tobacco interventions should be routinely offered in primary care. However, medical doctors do not consistently and effectively intervene during their encounters with cigarette smokers. There is a paucity of studies assessing the effect of training on the tobacco intervention competency of primary care doctors in Nigeria.AimTo evaluate the effectiveness of online training in improving competency in brief tobacco interventions among primary care doctors in Delta State, Nigeria.MethodsA cluster-randomised controlled trial was conducted among eligible doctors working in government-owned facilities. The 22 eligible Local Government Areas (LGAs) served as clusters. The intervention group received a WHO six-hour online course on brief tobacco cessation intervention, delivered via Zoom. The control group received no intervention. A structured questionnaire was sent to participants via WhatsApp before and six months after the training. The primary outcome variables were scores for knowledge, attitude, self-efficacy, and practice. Differences in change of scores between intervention and control groups were assessed witht-test. To adjust for clustering, these inter-group differences were further analysed using linear mixed-effects regression modelling with study condition modelled as a fixed effect, and LGA of practice entered as a random effect.ResultsThe intervention group had a significantly higher mean of change in scores for knowledge (effect size 0.344) and confidence (effect size 0.52).ConclusionThe study shows that training, even online, positively affects clinician competency in brief tobacco intervention. This is important for primary care systems in developing countries. Mandatory in-service training and promotion of the WHO modules are recommended.
Demographic responses of oceanic island birds to local and regional ecological disruptions revealed by whole-genome sequencing
Authors: Gabrielli Maëva , Leroy Thibault , Salmona Jordi , Nabholz Benoit , Milá Borja , Thébaud Christophe 
Published: September 2023

AbstractDisentangling the effects of ecological disruptions operating at different spatial and temporal scales in shaping past species’ demography is particularly important in the current context of rapid environmental changes driven by both local and regional factors. We argue that volcanic oceanic islands provide useful settings to study the influence of past ecological disruptions operating at local and regional scales on population demographic histories. We investigate potential drivers of past population dynamics for three closely related species of passerine birds from two volcanic oceanic islands, Reunion and Mauritius (Mascarene archipelago), with distinct volcanic history. Using ABC and PSMC inferences from complete genomes, we reconstructed the demographic history of the Reunion Grey White-eye (Zosterops borbonicus(Pennant, 1781)), the Reunion Olive White-eye (Z. olivaceus(Linnaeus, 1766)), and the Mauritius Grey White-eye (Z. mauritianus(Gmelin, 1789)), and searched for possible causes underlying similarities or differences between species living on the same or different islands. Both demographic inferences strongly support ancient and long-term expansions in all species. They also reveal different trajectories between species inhabiting different islands, but consistent demographic trajectories in species or populations from the same island. Species from Reunion appear to have experienced synchronous reductions in population size during the Last Glacial Maximum, a trend not seen in the Mauritian species. Overall, this study suggests that local events may have played a role in shaping population trajectories of these island species. It also highlights the potential of our conceptual framework to disentangle the effects of local and regional drivers on past species’ demography and long-term population processes.
Protein phosphatase 1 regulates core PCP signaling
Authors: Song Song , Cho Bomsoo , Weiner Alexis T. , Nissen Silas Boye , Naharros Irene Ojeda , Bosch Pablo Sanchez , Suyama Kaye , Hu Yanhui , He Li , Svinkina Tanya , Udeshi Namrata D. , Carr Steven A. , Perrimon Norbert , Axelrod Jeffrey D. 
Published: September 2023

AbstractPCP signaling polarizes epithelial cells within the plane of an epithelium. Core PCP signaling components adopt asymmetric subcellular localizations within cells to both polarize and coordinate polarity between cells. Achieving subcellular asymmetry requires additional effectors, including some mediating post-translational modifications of core components. Identification of such proteins is challenging due to pleiotropy. We used mass spectrometry-based proximity labeling proteomics to identify such regulators in theDrosophilawing. We identified the catalytic subunit of Protein Phosphatase1, Pp1-87B, and show that it regulates core protein polarization. Pp1-87B interacts with the core protein Van Gogh and at least one Serine/Threonine kinase, Dco/CKIc, that is known to regulate PCP. Pp1-87B modulates Van Gogh subcellular localization and directs its dephosphorylation in vivo. PNUTS, a Pp1 regulatory subunit, also modulates PCP. While the direct substrate(s) of Pp1-87B in control of PCP is not known, our data support the model that cycling between phosphorylated and unphosphorylated forms of one or more core PCP components may regulate acquisition of asymmetry. Finally, our screen serves as a resource for identifying additional regulators of PCP signaling.
Finding Drug Repurposing Candidates for Neurodegenerative Diseases using Zebrafish Behavioral Profiles
Authors: Del Rosario Hernández Thaís , Gore Sayali V , Kreiling Jill A , Creton Robbert 
Published: September 2023

AbstractDrug repurposing can accelerate drug development while reducing the cost and risk of toxicity typically associated with de novo drug design. Several disorders lacking pharmacological solutions and exhibiting poor results in clinical trials - such as Alzheimer’s disease (AD) - could benefit from a cost-effective approach to finding new therapeutics. We previously developed a neural network model, Z-LaP Tracker, capable of quantifying behaviors in zebrafish larvae relevant to cognitive function, including activity, reactivity, swimming patterns, and optomotor response in the presence of visual and acoustic stimuli. Using this model, we performed a high-throughput screening of FDA-approved drugs to identify compounds that affect zebrafish larval behavior in a manner consistent with the distinct behavior induced by calcineurin inhibitors. Cyclosporine (CsA) and other calcineurin inhibitors have garnered interest for their potential role in the prevention of AD. We generated behavioral profiles suitable for cluster analysis, through which we identified 64 candidate therapeutics for neurodegenerative disorders.
Conformation Selection by ATP-competitive Inhibitors and Allosteric Communication in ERK2
Authors: Anderson Jake W. , Vaisar David , Jones David N. , Pegram Laurel M. , Vigers Guy P. , Chen Huifen , Moffat John G. , Ahn Natalie G. 
Published: September 2023

ABSTRACTActivation of the extracellular signal regulated kinase-2 (ERK2) by phosphorylation has been shown to involve changes in protein dynamics, as determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) and NMR relaxation dispersion measurements. These can be described by a global exchange between two conformational states of the active kinase, named “L” and “R”, where R is associated with a catalytically productive ATP-binding mode. An ATP-competitive ERK1/2 inhibitor, Vertex-11e, has properties of conformation selection for the R-state, revealing movements of the activation loop that are allosterically coupled to the kinase active site. However, the features of inhibitors important for R-state selection are unknown. Here we survey a panel of ATP-competitive ERK inhibitors using HDX-MS and NMR and identify 14 new molecules with properties of R-state selection. They reveal effects propagated to distal regions in the P+1 and helix αF segments surrounding the activation loop, as well as helix αL16. Crystal structures of inhibitor complexes with ERK2 reveal systematic shifts in the Gly loop and helix αC, mediated by a Tyr-Tyr ring stacking interaction and the conserved Lys-Glu salt bridge. The findings suggest a model for the R-state involving small movements in the N-lobe that promote compactness within the kinase active site and alter mobility surrounding the activation loop. Such properties of conformation selection might be exploited to modulate the protein docking interface used by ERK substrates and effectors.
Influence of Microbiome on Withdrawal-Like Behavior in Planaria
Authors: Sosa Enrique Mentado , Pisciotta John M. , Guerra-Solano Miguel , Pagan One 
Published: September 2023

AbstractThe microbiome of animals can influence health status, disease susceptibility and can also influence host behavior. This study investigates the effect of microbiome alteration on animal behavior using the planarian model system. For this,Girardia tigrina(Brown Planaria) andPhagocata gracilis(Black Planaria) were investigated. These flatworms possess a primitive nervous system and exhibit similar addictive and withdrawal behaviors to mammals. Here we tested the hypothesis that alteration of planarian microbiome using the broad-spectrum antibiotics kanamycin and ampicillin could influence the worms’ behavior and withdrawal response to nicotine. After antibiotic treatment period of seven days, the behavior and withdrawal response of four groups of brown and black planaria was analyzed by recording the worms’ motility on a 1 cm2grid. Results support the hypothesis as treatment significantly altered behavior in black worms. The microbiomes of antibiotic treated planaria were analyzed using conventional culture techniques, microscopy and metagenomic methods. Alpha proteobacteria including Sphingomonadaceae were detected in both Brown and Black planarians. This study suggests chemotherapeutic alteration of an animal’s microbiome can influence motility behavior and withdrawal responses to addictive substance and sheds light on the species composition of Planarian microbiomes.
Concurrent administration of COVID-19 and influenza vaccines enhances Spike-specific antibody responses
Authors: Barouch Susanna E. , Chicz Taras M. , Blanc Ross , Barbati Domenic R. , Parker Lily J. , Tong Xin , McNamara Ryan P. 
Published: September 2023

ABSTRACTThe bivalent COVID-19 mRNA boosters became available in fall 2022 and were recommended alongside the seasonal influenza vaccine. However, the immunogenicity of concurrent versus separate administration of these vaccines remains unclear. Here, we analyzed antibody responses in healthcare workers who received the bivalent COVID-19 booster and the influenza vaccine on the same day or different days. IgG1 responses to SARS-CoV-2 Spike were higher at peak immunogenicity and 6 months following concurrent administration compared with separate administration of the COVID-19 and influenza vaccines. These data suggest that concurrent administration of these vaccines may yield higher and more durable SARS-CoV-2 antibody responses.
Heterologous expression of insect IRs in transgenicDrosophila melanogaster
Authors: Cattaneo Alberto Maria , Crava Cristina M. , Walker William B 
Published: September 2023

AbstractAmong insect chemosensory receptors, the broadly conserved Ionotropic Receptors (IRs) remain some of the least investigated. Several studies have documented IR activation by recording insect’s neuronal activityin situ, some demonstrated their activation when expressed in oocytes fromXenopus, others made use of theDrosophila“ionotropic receptor decoders” to functionally mis-express IRs from the same species or from the closely relatedD. sechellia. Here we demonstrated that both substituting tuning IRs ofD. melanogasterand expressing heterologous IRs from other insects alongside theDrosophilanative ones result in functional heteromeric complexes. By these methods, we functionally characterized the IR41a1 subunit of the codling mothCydia pomonella, which demonstrated binding to polyamines with different pharmacological characteristics and the IR75d subunit of the spotted wing drosophilaDrosophila suzukii, which binds hexanoic acid. Then we expressed theD. suzukiiacid sensor IR64a into theD. melanogaster“ionotropic receptor decoder” neuron, which resulted in the inhibition to the main activators of other neurons housed in the same sensillum ofD. melanogaster, as an evidence of its possible functional expression, but it did not show response to acids.In situhybridization on the antennae ofD. suzukiiunveiled a wide expression of this subunit in neurons proximal to the sacculus. Structural analysis did not explain absence of IR64a binding to acids, but it identified key amino acid features that may justify possible hexanoic acid binding for IR75d. While our findings add to the derophanization efforts conducted on the chemosensors of the aforementioned pests, they demonstrated potential for the use of neurons of transgenicDrosophilaas a tool to functionally characterize IRs from different insect species.
Neuronal correlates of time integration into memories
Authors: Frantzmann Felix , Lamberty Marius , Braune Laurin , Auger Genevieve M. , Chouhan Nitin Singh , Langenhan Tobias , Selcho Mareike , Pauls Dennis 
Published: September 2023

ABSTRACTThe circadian clock affects a wide range of physiological processes. Of particular interest is the influence of the clock on memory performance, as circadian dysfunction is associated with age- and disease-related decline in memory. In various species it has been shown that memory performance is regulated by the circadian clock. However, the anatomical and functional connection of the circadian clock and memory neurons has not been described in detail so far. This study now identifies that Diuretic hormone 31 (DH31)-positive clock neurons of the DN1p cluster regulate memory performance. DH31, a functional homolog of the mammalian calcitonin gene-related peptide, plays a crucial role in this process as a clock communication signal. DH31 facilitates memory performance during the night via indirect signalling, while DH31 signals directly to the mushroom bodies restricting memory performance specifically in the evening. This pleiotropic action of DH31 suggests that the circadian clock confines memory performance to a physiological dynamic range.
Bibliometric analysis of neuroscience publications quantifies the impact of data sharing
Authors: Emissah Herve , Ljungquist Bengt , Ascoli Giorgio A. 
Published: September 2023

AbstractMotivationNeural morphology, the branching geometry of neurons and glia in the nervous system, is an essential cellular substrate of brain function and pathology. Despite the accelerating production of digital reconstructions of neural morphology in laboratories worldwide, the public accessibility of data remains a core issue in neuroscience. Deficiencies in the availability of existing data create redundancy of research efforts and prevent researchers from building on others’ work. Data sharing complements the development of computational resources and literature mining tools to accelerate scientific discovery.ResultsWe carried out a comprehensive bibliometric analysis of neural morphology publications to quantify the impact of data sharing in the neuroscience community. Our findings demonstrate that sharing digital reconstructions of neural morphology via the NeuroMorpho.Org online repository leads to a significant increase of citations to the original article, thus directly benefiting the authors. Moreover, the rate of data reusage remains constant for at least 16 years after sharing (the whole period analyzed), altogether nearly doubling the peer-reviewed discoveries in the field. Furthermore, the recent availability of larger and more numerous datasets fostered integrative meta-analysis applications, which accrue on average twice the citations of re-analyses of individual datasets. We also designed and deployed an open-source citation tracking web-service that allows researchers to monitor reusage of their datasets in independent peer-reviewed reports. These results and the released tool can facilitate the recognition of shared data reuse for promotion and tenure considerations, merit evaluations, and funding decisions.Availability and implementationThe code is available athttps://github.com/HerveEmissah/nmo-authors-app(author app) andhttps://github.com/HerveEmissah/nmo-bibliometric-analysis(bibliometric analysis app).