bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interrogating Changes in COVID-19 Vaccine Intent During the National Vaccine Rollout in the Philippines
Authors: Caple Alexandria , Dimaano Arnie , Sagolili Marc Martin , Uy April Anne , Aguirre Panjee Mariel , Alano Dean , Baul Kaila Andrine , Camaya Giselle Sophia , Carlos Angelo Raine , Ciriaco Brent John , Clavo Princess Jerah Mae , Cuyugan Dominic , Fermo Cleinne Florence Geeseler , Lanete Paul Jeremy , La Torre Ardwayne Jurel , Loteyro Thomas , Lua Raisa Mikaela , Manansala Nicole Gayle , Mosquito Raphael , Octaviano Alexa Marie , Orfanel Alexandra Erika , Papa Anne Elizabeth , Pascual Gheyanna Merly , Peralta Mark Nhel , Sale Aubrey Joy , Tendenilla Sophia Lorraine , Trinidad Maria Sofia Lauren , Trinidad Nicole Jan , Verano Daphne Louise , Austriaco Nicanor 
Published: January 2024

AbstractTo mitigate the unprecedented health, social, and economic damage of COVID-19, the Philippines implemented a nation-wide vaccine program to mitigate the effects of the global pandemic. In a previous study, we interrogated COVID-19 vaccine intent in the country by deploying a nationwide open-access online survey, two months before the initial rollout of the national vaccination program that began in March of 2021. In this follow-up study, we explored the influence of the ongoing vaccine rollout on vaccine intent by deploying a similar survey six months after the initial rollout of vaccines had begun throughout the archipelago. Our data suggests that the presence of vaccines and vaccinated individuals in a Filipino community predicts vaccination intent. When directly asked if they were more willing to receive a vaccination than six months prior, 92.26% agreed to some extent that they were indeed more willing. Finally, despite the changes in the numbers of respondents who were more open to the COVID-19 vaccines, there were no significant changes in the predictive power of our Health Belief Model (HBM) constructs. For the most part, the HBM factors that predicted vaccination intent in our earlier study also predicted vaccination intent in this current study.
Pre-operative Spine Tumor Embolization: Clinical Outcomes and Effect of Embolization Completeness
Authors: Omid-Fard Nima , Salameh Jean-Paul , McInnes Matthew DF , Fisher Charles G , Heran Manraj KS 
Published: January 2024

AbstractBackground and PurposeTo assess the association between the impact of the completeness of pre-operative spine tumour embolization and clinical outcomes including estimated blood loss (EBL), neurological status, and complications.Materials and MethodsRetrospective chart review of all preoperative spine tumour embolization procedures performed over 11 years by a single operator (2007-2018) at Vancouver General Hospital, on 40 consecutive patients (mean age 58; 77.5% males) with 42 embolization procedures, of which surgery was done en bloc in 22 cases and intralesional in the remaining 20. A multivariable negative binomial regression model was fit to examine the association between EBL and surgery type, tumour characteristics, embolization completeness and operative duration.ResultsAmong intralesional surgeries, complete versus incomplete embolization was associated with reduced blood loss (772 vs 1428 mL, P < 0.001). There was no statistically significant difference in neurological outcomes or complications between groups. Highly vascular tumours correlated with greater blood loss than their less vascular counterparts, but tumour location did not have a statistically significant effect.ConclusionThis study provides early evidence in support of our hypothesis that complete as opposed to incomplete tumour embolization correlates with reduced blood loss in intralesional surgeries. Randomized control trials with larger samples are necessary to confirm this benefit and to ascertain other potential clinical benefits.
‘Involve those, who are managing these outbreaks’– Identifying barriers and facilitators to the implementation of clinical management guidelines for High-Consequence Infectious Diseases in Uganda
Authors: Kabajaasi Olive , Schilling Stefan , Akugizibwe Mathias , Horby Peter , Hart Peter , Sigfrid Louise , Jacob Shevin T. 
Published: January 2024

ABSTRACTPrior research highlighting the complexity of clinical management guidelines (CMG) implementation, has suggested that limited access to treatments and equipment [1] and substantial issues regarding availability, inclusivity, quality, and applicability [2–6] hinder the implementation of CMGs in Low- and Middle-Income Countries (LMICs). This in-depth case study of Uganda – coincidentally occurring during the 2022 Sudan Virus Disease outbreak – aimed to explore contextual and supplementary factors which hinder or facilitate CMG development and implementation. Using thematic network analysis [7–9] the research describes five thematic topics, that emerged from interviews with 43 healthcare personnel, as barriers to the implementation of CMGs in Uganda, namely: (1) deficient content and slow updates of CMGs; (2) limited pandemic preparedness and response infrastructure; (3) slow dissemination and lack of training; (4) scarce resources and healthcare disparities and (5) patient outcomes. The study displays how insufficient training, patchy dissemination and slow updating exacerbate many of the underlying difficulties in LMIC contexts, by illustrating how these issues are related to resource constraints, healthcare disparities, and limited surveillance and referral infrastructure. Key recommendations to enhance CMG implementation are provided, underscoring the necessity of integrating local stakeholders to ensure guidelines are reflective of the reality of the local health system, applicable and inclusive of resource-constrained settings, available as “living guidance” that is disseminated widely and supported by cascading hands-on training. Findings offer valuable insights for LMICs to improve high consequence infectious disease outbreak responses and for organizations involved in guideline development and funding.
Enhanced Patient Portal Engagement Associated with Improved Weight Loss Outcomes in Post-Bariatric Surgery Patients
Authors: Zhang Xinmeng , Kang Kaidi , Yan Chao , Feng Yubo , Vandekar Simon , Yu Danxia , Rosenbloom S. Trent , Samuels Jason , Srivastava Gitanjali , Williams Brandon , Albaugh Vance L. , English Wayne J. , Flynn Charles R. , Chen You 
Published: January 2024

AbstractBackgroundBariatric surgery is an effective intervention for obesity, but it requires comprehensive postoperative self-management to achieve optimal outcomes. While patient portals are generally seen as beneficial in engaging patients in health management, the link between their use and post-bariatric surgery weight loss remains unclear.ObjectiveThis study investigated the association between patient portal engagement and postoperative body mass index (BMI) reduction among bariatric surgery patients.MethodsThis retrospective longitudinal study included patients who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at Vanderbilt University Medical Center (VUMC) between January 2018 and March 2021. Using generalized estimating equations, we estimated the association between active days of postoperative patient portal use and the reduction of BMI percentage (%BMI) at 3, 6, and 12 months post-surgery. Covariates included duration since surgery, the patient’s age at the time of surgery, gender, race and ethnicity, type of bariatric surgery, severity of comorbid conditions, and socioeconomic disadvantage.ResultsThe study included 1,415 patients, mostly female (80.9%), with diverse racial and ethnic backgrounds. 805 (56.9%) patients underwent RYGB and 610 (43.1%) underwent SG. By one-year post-surgery, the mean (SD) %BMI reduction was 31.1% (8.3%), and the mean (SD) number of patient portal active days was 61.0 (41.2). A significantly positive association was observed between patient portal engagement and %BMI reduction, with variations revealed over time. Each 10-day increment of active portal use was associated with a 0.57% ([95% CI: 0.42- 0.72],P< .001) and 0.35% ([95% CI: 0.22- 0.49],P< .001) %BMI reduction at 3 and 6 months postoperatively. The association was not statistically significant at 12 months postoperatively (β=-0.07, [95% CI: -0.24- 0.09],P= .54). Various portal functions, including messaging, visits, my record, medical tools, billing, resources, and others, were positively associated with %BMI reduction at 3- and 6-months follow-ups.ConclusionsGreater patient portal engagement, which may represent stronger adherence to postoperative instructions, better self-management of health, and enhanced communication with care teams, was associated with improved postoperative weight loss. Future investigations are needed to identify important portal features that contribute to the long-term success of weight loss management.
Major depressive disorder, neuroticism, suicidal behaviors, and depression severity are all associated with neurotoxic immune networks and their intricate interactions with metabolic syndrome
Authors: Maes Michael , Jirakran Ketsupar , Vasupanrajit Asara , Zhou Bo , Tunvirachaisakul Chavit , Almulla Abbas F. 
Published: January 2024

AbstractBackgroundMajor depressive disorder (MDD) is considered to be a neuroimmune disorder. However, there are no data regarding the association between comprehensive immune profiles and their interactions with the metabolic syndrome (MetS) in predicting neuroticism, suicidal behaviors, and severity of outpatient MDD (OMDD).MethodsWe assayed 48 serum cytokines, chemokines, and growth factors using a multiplex assay in 67 healthy controls and 66 OMDD patients. Around 50% of the OMDD and control participants had a diagnosis of MetS.ResultsTen differentially expressed proteins (DEPs) were upregulated in OMDD (i.e., CXCL12, TNFB, PDGF, CCL11, IL9, IL4, CCL5, CCL2, CCL4, IL1RN), indicating an immune, defense and stress response. Six DEPs were downregulated (VEGFA, IL12, CCL3, CSF1, IL1B, NGF), indicating lowered neurogenesis and regulation of neuron death. Significant interactions between OMDD and MetS caused a) substantial increases in TNF signaling, and upregulation of IL4, IL17, TNF, TNFB, CCL2, CCL5, PDGF, IL1RN; and b) downregulation of VEGFA and FGF. A large part of the variance in neuroticism (26.6%), suicidal behaviors (23.6%), and the MDD phenome (31.4%) was predicted by immunological data and interactions between MetS and CCL5, TNFB or VEGFA.DiscussionOMDD is characterized by an immunoneurotoxic profile which partly explains neuroticism, suicidal behaviors, and the phenome’s severity. Lowered IL-10 and increased neurotoxicity are characteristics of OMDD and other depression phenotypes, including severe first-episode inpatient MDD. The presence of MetS in OMDD considerably exacerbates immunoneurotoxicity. Consequently, immune studies in MDD should always be performed in subjects with and without MetS.
Activational and organizational effects of sex hormones on hippocampal inhibitory neurons
Authors: Hernández-Vivanco Alicia , de la Vega-Ruiz Rut , Montes-Mellado Alberto , Azcoitia Íñigo , Méndez Pablo 
Published: January 2024

AbstractPeripheral and brain-produced sex hormones exert sex-specific regulation of hippocampal cognitive function. Estrogens produced by neuronal aromatase regulate inhibitory neurons (INs) and hippocampal-dependent memory in adult female mice, but not in males. How and when this sex effect is stablished and how peripheral and brain sources of estrogens interact in the control of hippocampal INs is currently unknown. Using ex-vivo electrophysiology, fiber photometry, molecular analysis, estrous cycle monitoring and neonatal hormonal manipulations, we unveil estrous cycle dependent and independent features of CA1 Parvalbumin (PV) INs and hippocampal inhibition in adult female mice. Before puberty, aromatase is expressed in PV INs and regulates synaptic inhibition in female but not in male mice. Neonatal testosterone administration altered prepubertal female mice hippocampal dependent memory, PV IN function and estrogenic regulation of adult female synaptic inhibition and PV INs perineuronal nets. Our results suggest that sex differences in brain-derived estrogen regulation of CA1 inhibition are established by organizational effects of neonatal gonadal hormones and highlight the role of INs as mediators of the sexual differentiation of the hippocampus.HighlightsEstrous cycle dependent and independent features of CA1 PV INs and hippocampal inhibitionAromatase is expressed in male and female PV neurons before puberty.Neuroestrogens regulate prepubertal CA1 synaptic inhibition in females but not in males.Neonatal testosterone disrupts neuroestrogen effects on adult female hippocampus.Neonatal testosterone affects PV INs and hippocampal function before puberty.
Higher-order epistasis within Pol II trigger loop haplotypes
Authors: Duan Bingbing , Qiu Chenxi , Lockless Steve W. , Sze Sing-Hoi , Kaplan Craig D. 
Published: January 2024

ABSTRACTRNA polymerase II (Pol II) has a highly conserved domain, the trigger loop (TL), that controls transcription fidelity and speed. We previously probed pairwise genetic interactions between residues within and surrounding the TL for the purpose of understand functional interactions between residues and to understand how individual mutants might alter TL function. We identified widespread incompatibility between TLs of different species when placed in theSaccharomyces cerevisiaePol II context, indicating species-specific interactions between otherwise highly conserved TLs and its surroundings. These interactions represent epistasis between TL residues and the rest of Pol II. We sought to understand why certain TL sequences are incompatible withS. cerevisiaePol II and to dissect the nature of genetic interactions within multiply substituted TLs as a window on higher order epistasis in this system. We identified both positive and negative higher-order residue interactions within example TL haplotypes. Intricate higher-order epistasis formed by TL residues was sometimes only apparent from analysis of intermediate genotypes, emphasizing complexity of epistatic interactions. Furthermore, we distinguished TL substitutions with distinct classes of epistatic patterns, suggesting specific TL residues that potentially influence TL evolution. Our examples of complex residue interactions suggest possible pathways for epistasis to facilitate Pol II evolution.
Mechanisms of gas sensing by internal sensory neurons inDrosophilalarvae
Authors: Lu Shan , Qian Cheng Sam , Grueber Wesley B. 
Published: January 2024

ABSTRACTInternal sensory neurons monitor the chemical and physical state of the body, providing critical information to the central nervous system for maintaining homeostasis and survival. A population of larvalDrosophilasensory neurons, tracheal dendrite (td) neurons, elaborate dendrites along respiratory organs and may serve as a model for elucidating the cellular and molecular basis of chemosensation by internal neurons. We find that td neurons respond to decreases in O2levels and increases in CO2levels. We assessed the roles of atypical soluble guanylyl cyclases (Gycs) and a gustatory receptor (Gr) in mediating these responses. We found that Gyc88E/Gyc89Db were necessary for responses to hypoxia, and that Gr28b was necessary for responses to CO2. Targeted expression of Gr28b isoform c in td neurons rescued responses to CO2in mutant larvae and also induced ectopic sensitivity to CO2in the td network. Gas-sensitive td neurons were activated when larvae burrowed for a prolonged duration, demonstrating a natural-like feeding condition in which td neurons are activated. Together, our work identifies two gaseous stimuli that are detected by partially overlapping subsets of internal sensory neurons, and establishes roles for Gyc88E/Gyc89Db in the detection of hypoxia, and Gr28b in the detection of CO2.
Viroid-like colonists of human microbiomes
Authors: Zheludev Ivan N. , Edgar Robert C. , Lopez-Galiano Maria Jose , de la Peña Marcos , Babaian Artem , Bhatt Ami S. , Fire Andrew Z. 
Published: January 2024

AbstractHere, we describe the “Obelisks,” a previously unrecognised class of viroid-like elements that we first identified in human gut metatranscriptomic data. “Obelisks” share several properties: (i) apparently circular RNA ∼1kb genome assemblies, (ii) predicted rod-like secondary structures encompassing the entire genome, and (iii) open reading frames coding for a novel protein superfamily, which we call the “Oblins”. We find that Obelisks form their own distinct phylogenetic group with no detectable sequence or structural similarity to known biological agents. Further, Obelisks are prevalent in tested human microbiome metatranscriptomes with representatives detected in ∼7% of analysed stool metatranscriptomes (29/440) and in ∼50% of analysed oral metatranscriptomes (17/32). Obelisk compositions appear to differ between the anatomic sites and are capable of persisting in individuals, with continued presence over >300 days observed in one case. Large scale searches identified 29,959 Obelisks (clustered at 90% nucleotide identity), with examples from all seven continents and in diverse ecological niches. From this search, a subset of Obelisks are identified to code for Obelisk-specific variants of the hammerhead type-III self-cleaving ribozyme. Lastly, we identified one case of a bacterial species (Streptococcus sanguinis) in which a subset of defined laboratory strains harboured a specific Obelisk RNA population. As such, Obelisks comprise a class of diverse RNAs that have colonised, and gone unnoticed in, human, and global microbiomes.
Multipad Agarose Plate (MAP): A Rapid and High-Throughput Approach for Antibiotic Susceptibility Testing
Authors: Kals Morten , Mancini Leonardo , Kotar Jurij , Donald Allen , Cicuta Pietro 
Published: January 2024

AbstractWe describe a phenotypic antibiotic susceptibility testing (AST) method that can provide an eightfold speedup in turnaround time compared to the current clinical standard by leveraging advances in microscopy and single-cell imaging. A newly developed growth plate containing 96 agarose pads, termed the Multipad Agarose Plate (MAP), can be assembled at low costs. Pads can be prepared with dilution series of antibiotics. Bacteria are seeded on the pads and automatically imaged using brightfield microscopy, with a fully automated segmentation pipeline quantifying microcolony formation and growth rate. Using a test set of nine antibiotics with very different targets, we demonstrate that accurate minimum inhibitory concentration (MIC) measurements can be performed based on the growth rate of microcolonies within three hours of incubation with the antibiotic. Faster, reliable and high throughput methods for AST, such as MAP, could improve patient care by expediting treatment initiation and alleviating the burden of antimicrobial resistance.
ByeTAC: Bypassing an E3 Ligase for Targeted Protein Degradation
Authors: Ali Eslam M. H. , Loy Cody A. , Trader Darci J. 
Published: January 2024

AbstractTargeted protein degradation utilizing a bifunctional molecule to initiate ubiquitination and subsequent degradation by the 26S proteasome has been shown to be a powerful therapeutic intervention. Many bifunctional molecules, including covalent and non-covalent ligands to proteins of interest, have been developed. The traditional target protein degradation methodology targets the protein of interest in both healthy and diseased cell populations, and a therapeutic window is obtained based on the overexpression of the targeted protein. We report here a series of bifunctional degraders that do not rely on interacting with an E3 ligase, but rather a 26S proteasome subunit, which we have named ByeTACs: Bypassing E3 Targeting Chimeras. Rpn-13 is a non-essential ubiquitin receptor for the 26S proteasome. Cells under significant stress or require significant ubiquitin-dependent degradation of proteins for survival, incorporate Rpn-13 in the 26S to increase protein degradation rates. The targeted protein degraders reported here are bifunctional molecules that include a ligand to Rpn-13 and BRD4, the protein of interest we wish to degrade. We synthesized a suite of degraders with varying PEG chain lengths and showed that bifunctional molecules that incorporate a Rpn-13 binder (TCL1) and a BRD4 binder (JQ1) with a PEG linker of 3 or 4 units are the most effective to induce BRD4 degradation. We also demonstrate that our new targeted protein degraders are dependent upon proteasome activity and Rpn-13 expression levels. This establishes a new mechanism of action for our ByeTACs that can be employed for the targeted degradation of a wide variety of protein substrates.
Behavioral sequences across multiple animal species in the wild share common structural features
Authors: Minasandra Pranav , Grout Emily M , Brock Katrina , Crofoot Margaret C , Demartsev Vlad , Gersick Andrew S , Hirsch Ben T , Holekamp Kay E , Johnson-Ulrich Lily , Nayak Amlan , Ortega Josué , Roch Marie A , Strauss Eli D , Strandburg-Peshkin Ariana 
Published: January 2024

AbstractAnimal behavior can be decomposed into a sequence of discrete activity bouts over time. Analyzing the statistical structure of such behavioral sequences can provide insights into the drivers of behavioral decisions. Laboratory studies, predominantly in invertebrates, have suggested that behavioral sequences exhibit multiple timescales and long-range memory, but whether these results can be generalized to other taxa and to animals in natural settings remains unclear. By analyzing accelerometer-inferred predictions of behavioral states in three species of social mammals (meerkats, white-nosed coatis, and spotted hyenas) in the wild, we discovered surprisingly consistent structuring of behavioral sequences across all behavioral states, all individuals, and all study species. Behavioral bouts were characterized by decreasing hazard functions, wherein the longer a behavioral bout had progressed, the less likely it was to end within the next instant. The predictability of an animal’s future behavioral state as a function of its present state always decreased as a truncated power-law for predictions made farther into the future, with very similar estimates for the power law exponent across all species. Finally, the distributions of bout durations were also heavy-tailed. Why such shared structural principles emerge remains unknown, and we explore multiple plausible explanations, including environmental non-stationarity, behavioral self-reinforcement, and the hierarchical nature of behavior. The existence of highly consistent patterns in behavioral sequences across our study species suggests that these phenomena could be widespread in nature, and points to the existence of fundamental properties of behavioral dynamics that could drive such convergent patterns.Significance statementThe study of animal behavior seeks to understand how and why animals do what they do. This pursuit of general principles governing behavior across species can be approached by first understandingwhenanimals choose to change their behavioral states (e.g., switching from walking to standing, or to running). Using accelerometer-inferred behaviors of three social mammals, we uncover common structural ‘long timescale’ patterns in their sequences of behavior. We explore two explanations, involving either positive feedbacks or the interaction of several independent time-scales, about how such common patterns arise.