bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstraction of reward context facilitates relative reward coding in neural populations of the anterior cingulate cortex
Authors: Chien Jonathan M. , Wallis Joni D. , Rich Erin L. 
Published: December 2022

AbstractThe anterior cingulate cortex (ACC) is believed to be involved in many cognitive processes, including linking goals to actions and tracking decision-relevant contextual information. ACC neurons robustly encode expected outcomes, but how this relates to putative functions of ACC remains unknown. Here, we approach this question from the perspective of population codes by analyzing neural spiking data in the ventral and dorsal banks of the ACC in monkeys trained to perform a stimulus-motor mapping task. We found that neural populations favor a representational geometry that emphasizes contextual information, while facilitating the independent, abstract representation of multiple task-relevant variables. In addition, trial outcomes were primarily encoded relative to task context, suggesting that the population structures we observe could be a mechanism allowing feedback to be interpreted in a context-dependent manner. Together, our results point to a prominent role for ACC in context-setting and relative interpretation of outcomes, facilitated by abstract, or “untangled,” representations of task variables.Author SummaryThe ability to interpret events in light of the current context is a critical facet of higher-order cognition. The anterior cingulate cortex is suggested to be important for tracking information about current contexts, while alternate views hold that its function is more related to the motor system and linking goals to appropriate motor responses. Here, we evaluated these two possibilities by recording anterior cingulate neurons from monkeys performing a stimulus-motor mapping task in which compound cues both defined the current reward context and instructed appropriate motor responses. By analyzing geometric properties of neural population activity, we found that the ACC prioritized context information, representing it as a dominant, abstract concept. Ensuing trial outcomes were then coded relative to these contexts, suggesting an important role for these representations in context-dependent evaluation. Such mechanisms may be critical for the abstract reasoning and generalization characteristic of biological intelligence.
PYPE: A Python pipeline for phenome-wide association (PheWAS) and mendelian randomization in investigator-driven phenotypes and genotypes of biobank data
Authors: Dalal Taykhoom , Patel Chirag J. 
Published: December 2022

AbstractMotivationPhenome-wide association studies (PheWASs) serve as a way of documenting the relationship between genotypes and multiple phenotypes, helping to uncover new and unexplored genotype-phenotype associations (known as pleiotropy). Secondly, Mendelian Randomization (MR) can be harnessed to make causal statements about a pair of phenotypes (e.g., does one phenotype cause the other?) by comparing the genetic architecture of the phenotypes in question. Thus, approaches that automate both PheWAS and MR can enhance biobank scale analyses, circumventing the need for multiple bespoke tools for each task by providing a comprehensive, end-to-end pipeline to drive scientific discovery.ResultsWe present PYPE, a Python pipeline for running, visualizing, and interpreting PheWAS. Our pipeline allows the researcher to input genotype or phenotype files from the UK Biobank (UKBB) and automatically estimate associations between the chosen independent variables and the phenotypes. PYPE also provides a variety of visualization options including Manhattan and volcano plots and can be used to identify nearby genes and functional consequences of the significant associations. PYPE additionally provides the user with the ability to run Mendelian Randomization (MR) under a variety of causal effect modeling scenarios (e.g., Inverse Variance Weighted Regression, Egger Regression, and Weighted Median Estimation) to identify possible causal relationships between phenotypes.Availability and ImplementationPYPE is a free, open-source project developed entirely in Python and can be found athttps://github.com/TaykhoomDalal/pype. PYPE is published under the Apache 2.0 license and supporting documentation can be found at the aforementioned link.ContactChirag_Patel@hms.harvard.edu
Bulk and Mosaic Deletions ofEgfrReveal Regionally Defined Gliogenesis in the Developing Mouse Forebrain
Authors: Zhang Xuying , Xiao Guanxi , Johnson Caroline , Cai Yuheng , Horowitz Zachary K. , Mennicke Christine , Coffey Robert , Haider Mansoor , Threadgill David , Eliscu Rebecca , Oldham Michael C. , Greenbaum Alon , Ghashghaei H. Troy 
Published: December 2022

SummaryThe Epidermal growth factor receptor (EGFR) plays a role in cell proliferation and differentiation during healthy development and tumor growth, however its requirement for brain development remains unclear. Here we used a conditional mouse allele forEgfrto examine its contributions to perinatal forebrain development at the tissue level. Subtractive bulk ventral and dorsal forebrain deletions ofEgfruncovered significant and permanent decreases in oligodendrogenesis and myelination in the cortex and corpus callosum. Additionally, an increase in astrogenesis or reactive astrocytes in effected regions was evident in response to cortical scarring. Sparse deletion using Mosaic Analysis with Double Markers (MADM) surprisingly revealed a regional requirement for EGFR in rostrodorsal, but not ventrocaudal glial lineages including both astrocytes and oligodendrocytes. The EGFR-independent ventral glial progenitors may compensate for the missing EGFR-dependent dorsal glia in the bulkEgfr-deleted forebrain, potentially exposing a regenerative population of gliogenic progenitors in the mouse forebrain.
Spatial omics representation and functional tissue module inference using graph Fourier transform
Authors: Chang Yuzhou , Liu Jixin , Ma Anjun , Jiang Sizun , Krull Jordan , Yeo Yao Yu , Liu Yang , Rodig Scott J. , Barouch Dan H. , Fan Rong , Xu Dong , Nolan Garry , Li Zihai , Liu Bingqiang , Ma Qin 
Published: December 2022

AbstractTissue module (TM) is a spatially organized tissue region and executes specialized biological functions, recurring and varying at different tissue sites. However, the computational identification of TMs poses challenges due to their convoluted biological functions, poorly-defined molecular features, and varying spatially organized patterns. Here, we present a hypothesis-free graph Fourier transform model, SpaGFT, to represent spatially organized features using the Fourier coefficients, leading to an accurate representation of spatially variable genes and proteins and the characterization of TM at a fast computational speed. We implemented sequencing-based and imaging-based spatial transcriptomics, spatial-CITE-seq, and spatial proteomics to identify spatially variable genes and proteins, define TM identities, and infer convoluted functions among TMs in mouse brains and human lymph nodes. We collected a human tonsil sample and performed CODEX to accurately demonstrate molecular and cellular variability within the secondary follicle structure. The superior accuracy, scalability, and interpretability of SpaGFT indicate that it is an effective representation of spatially-resolved omics data and an essential tool for bringing new insights into molecular tissue biology.
Regime type and Data Manipulation: Evidence from the COVID-19 Pandemic
Authors: Wigley Simon 
Published: December 2022

AbstractAutocratic and democratic leaders have an incentive to misreport data that may reveal policy failure. However, it is easier for autocratic leaders to fabricate data because they are not subject to scrutiny from media, opposition parties, and civil society. This suggests that autocratic governments are more likely to manipulate policy-relevant statistics than democratic governments. It is inherently difficult to test that claim because researchers typically do not have access to data from sources other than the government. The COVID-19 pandemic represents a unique opportunity to examine the relationship between regime type and data manipulation because of its widespread impact, as well as the ability to compare reported with excess deaths and test for statistical anomalies in reported data. Based on regressions for undercounting and statistical irregularities that take into account unintentional mismeasurement, I find that autocratic governments are more likely to deliberately under-report the impact of COVID-19 than their democratic counterparts.
Distinct stem-like cell populations facilitate functional regeneration of theCladonemamedusa tentacle
Authors: Fujita Sosuke , Takahashi Mako , Kumano Gaku , Kuranaga Erina , Miura Masayuki , Nakajima Yu-ichiro 
Published: December 2022

AbstractBlastema formation is a crucial process that provides a cellular source for regenerating tissues and organs. While bilaterians have diversified blastema formation methods, its mechanisms in non-bilaterians remain poorly understood. Cnidarian jellyfish, or medusae, represent early-branching metazoans that exhibit complex morphology and possess defined appendage structures highlighted by tentacles with stinging cells (nematocytes). Here we investigate the mechanisms of tentacle regeneration, using the hydrozoan jellyfishCladonema pacificum. We show that proliferative cells accumulate at the tentacle amputation site and form a blastema composed of cells with stem cell morphology. Lineage tracing experiments indicate that repair-specific proliferative cells in the blastema are distinct from resident stem cells. We further demonstrate that resident stem cells control nematogenesis and tentacle elongation during both homeostasis and regeneration as homeostatic stem cells, while repair-specific proliferative cells preferentially differentiate into epithelial cells in the newly formed tentacle, analogous to lineage-restricted stem/progenitor cells observed in salamander limbs. Taken together, our findings reveal a regeneration mechanism that utilizes both resident homeostatic stem cells and repair-specific proliferative cells, which in conjunction efficiently enable functional appendage regeneration, and provide novel insight into the diversification of blastema formation across animal evolution.
The genetic basis of traits associated with the evolution of serpentine endemism in monkeyflowers
Authors: Toll Katherine , Willis John H. 
Published: December 2022

AbstractThe floras on chemically and physically challenging soils, such as gypsum, shale, and serpentine, are characterized by narrowly endemic species. These edaphic endemics often have widespread close relatives that are not restricted to specific soil types. The evolution of edaphic endemics may be facilitated or constrained by genetic correlations among traits contributing to adaptation and reproductive isolation across soil boundaries. The yellow monkeyflowers in theMimulus guttatusspecies complex are an ideal system in which to examine these evolutionary patterns. To determine the genetic basis of adaptive and prezygotic isolating traits, we performed genetic mapping experiments with F2 hybrids derived from a cross between a serpentine endemic,M. nudatus, and its close relativeM. guttatus. Plants occurring on serpentine soils have repeatedly evolved short statures and small leaves, suggesting that these traits are adaptive, andM. nudatusshows all these characteristics compared toM. guttatus. Previous research demonstrated that flower size and life history differences between these species contribute to prezygotic reproductive isolation between them. Few large effect and many small effect loci contribute to interspecific divergence in life history, floral and leaf traits, and a history of directional selection contributed to trait divergence. Loci contributing to adaptive traits and prezygotic reproductive isolation overlap, and their allelic effects are largely in the direction of species divergence. These loci contain promising candidate genes regulating flowering time and plant organ size. Together our results suggest that genetic correlations among traits facilitated the evolution of edaphic adaptation and speciation in this species pair.
COVID-19 Outbreak Control Strategies and their Impact on the Provision of Essential Health Services in Ghana: An Explanatory-Sequential Study
Authors: Dwomoh Duah , Yeboah Isaac , Ndejjo Rawlance , Kabwama Steven Ndugwa , Aheto Justice Moses , Liu Anne , Lazenby Siobhan , Ohemeng Fidelia , Takyi Sylvia Akpene , Issah Ibrahim , Bawuah Serwaa Akoto , Wanyenze Rhoda K. , Fobil Julius 
Published: December 2022

AbstractBackgroundThe COVID-19 pandemic has led to substantial interruptions in critical health services, with 90% of countries reporting interruptions in routine vaccinations, maternal health care and chronic disease management. The use of non-pharmaceutical interventions (NPIs) such as lockdowns and self-isolation had implications on the provision of essential health services (EHS). We investigated exemplary COVID-19 outbreak control strategies and explored the extent to which the adoption of these NPIs affected the provision of EHS including immunization coverage and facility-based deliveries. Finally, we document core health system strategies and practices adopted to maintain EHS during the early phase of the pandemic.MethodsThis study used an explanatory sequential study design. First, we utilized data from routine health management information systems to quantify the impact of the pandemic on the provision of EHS using interrupted time series models. Second, we explored exemplary strategies and health system initiatives that were adopted to prevent the spread of COVID-19 infections while maintaining the provision of EHS using in-depth interviews with key informants including policymakers and healthcare providers.ResultsThe COVID-19 pandemic and the interventions that were implemented disrupted the provision of EHS. In the first month of the COVID-19 pandemic, Oral Polio and pentavalent vaccination coverage reduced by 15.2% [95% CI = −22.61, −7.87, p<0.001] and 12.4% [95% CI = 17.68, −7.13; p<0.001] respectively. The exemplary strategies adopted in maintaining the provision of EHS while also responding to the spread of infections include the development of new policy guidelines that were disseminated with modified service delivery models, new treatment and prevention guidelines, healthcare workforce capacity building on outbreak control strategies, the use of telemedicine and medical drones to provide EHS and facilitate rapid testing of suspected cases.ConclusionThe implementation of different NPIs during the peak phase of the pandemic disrupted the provision of EHS. However, the Ministry of Health leveraged the resilient health system and deployed efficient, all-inclusive, and integrated infectious disease management and infection prevention control strategies to maintain the provision of EHS while responding to the spread of infections.
Pholcodine consumption increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: the ALPHO case-control study
Authors: Mertes Paul Michel , Petitpain Nadine , Tacquard Charles , Delpuech Marion , Baumann Cédric , Malinovsky Jean Marc , Longrois Dan , Gouel-Cheron Aurélie , Quang Diane Le , Demoly Pascal , Guéant Jean Louis , Gillet Pierre 
Published: December 2022

ABSTRACTBackgroundNeuromuscular blocking agents (NMBAs) are the leading cause of perioperative anaphylaxis (POA), most reactions being IgE mediated. Allergic sensitization induced by environmental exposure to other quaternary ammonium-containing compounds, such as pholcodine, has been suggested. The aim of this study was to assess the relationship between pholcodine exposure and NMBA-related POA.MethodsALPHO is a multicentre case-control study, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related POA (cases) and control patients with uneventful anaesthesia. Each case was matched to two controls by age, sex, type of NMBA, geographic area, and season. Pholcodine exposure was assessed by a self-administered questionnaire and pharmaceutical history retrieved from pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated.ResultsOverall, 167 cases were matched with 334 controls. NMBA-related POA was significantly associated with pholcodine consumption (OR =4.2; CI95% 2.3-7.0) and occupational exposure to quaternary ammoniums (OR = 6.1; CI95% 2.7-13.6). Anti-pholcodine and anti-quaternary ammonium sIgEs had a high negative predictive value (99.9%) but a very low positive predictive value (< 3%) for identifying NMBA-related POA.ConclusionPatients exposed to pholcodine 12 months prior to NMBA exposure have a significantly higher risk of a NMBA-related POA. The low positive predictive values of pholcodine and quaternary ammonium sIgEs precludes their use to identify a population with a high risk of NMBA-related POA. The strong association of NMBA-related POA with occupational exposure suggests that other environmental factors may also lead to sensitization to NMBAs.
Genomic characterization of respiratory syncytial virus 2022-2023 outbreak in Washington State, USA
Authors: Goya Stephanie , Sereewit Jaydee , Pfalmer Daniel , Nguyen Tien V. , Mohamed Bakhash Shah A. K. , Sobolik Elizabeth B. , Greninger Alexander L. 
Published: December 2022

AbstractMitigation measures against the COVID-19 pandemic affected the RSV seasonality and led to an unexpectedly high number of RSV cases in Washington State since October 2022. Here we describe the RSV genomic characteristics and evolutionary relationship of 2022 outbreak compared to the previous RSV outbreaks in the region and globally.
The COVID-19 pandemic and its prolonged impacts on food prices, food consumption and diet quality in sub-Saharan Africa
Authors: Ismail Abbas , Madzorera Isabel , Apraku Edward A. , Tinkasimile Amani , Dasmane Dielbeogo , Zabre Pascal , Ourohire Millogo , Assefa Nega , Chukwu Angela , Workneh Firehiwot , Mapendo Frank , Lankoande Bruno , Hemler Elena , Wang Dongqing , Abubakari Sulemana W. , Asante Kwaku P. , Baernighausen Till , Killewo Japhet , Oduola Ayoade , Sie Ali , Soura Abdramane , Vuai Said , Smith Emily , Berhane Yemane , Fawzi Wafaie W. 
Published: December 2022

AbstractBackgroundSub-Saharan Africa faces prolonged COVID-19 related impacts on economic activity, livelihoods, nutrition, and food security, with recovery slowed down by lagging vaccination progress.ObjectiveThis study investigated the economic impacts of COVID-19 on food prices, consumption and dietary quality in Burkina Faso, Ethiopia, Ghana, Nigeria, and Tanzania.MethodsWe conducted a repeated cross-sectional study and used a mobile platform to collect data. Data collected from round 1 (July-November, 2020) and round 2 (July-December, 2021) were considered. We assessed participants’ dietary intake of 20 food groups over the previous seven days. The study’s primary outcome was the Prime Diet Quality Score (PDQS), with higher scores indicating better dietary quality. We used linear regression and generalized estimating equations to assess factors associated with diet quality during COVID-19.ResultsMost of the respondents were male and the mean age (±SD) was 42.4 (±12.5) years. Mean PDQS (±SD) was low at 19.1 (±3.8) before COVID-19, 18.6(±3.4) in Round 1, and 19.4(±3.8) in Round 2. A majority of respondents (80%) reported higher than expected prices for all food groups during the pandemic. Secondary education or higher (estimate: 0.73, 95% CI: 0.32, 1.15), older age (estimate: 30-39 years: 0.77, 95% CI: 0.35, 1.19, or 40 years or older: 0.72, 95% CI: 0.30, 1.13), and medium wealth status (estimate: 0.48, 95% CI: 0.14, 0.81) were associated with higher PDQS. Farmers and casual laborers (estimate: -0.60, 95% CI: -1.11, - 0.09), lower crop production (estimate: -0.87, 95% CI: -1.28, -0.46) and not engaged in farming (estimate: -1.38, 95% CI: -1.74, -1.02) associated with lower PDQS.ConclusionDiet quality which had declined early in the pandemic had started to improve. However, consumption of healthy diets remained low, and food prices remained high. Efforts should continue to improve diet quality for sustained nutrition recovery through mitigation measures, including social protection.
Live-attenuated pediatric parainfluenza vaccine expressing 6P-stabilized SARS-CoV-2 spike protein is protective against SARS-CoV-2 variants in hamsters
Authors: Liu Xueqiao , Park Hong-Su , Matsuoka Yumiko , Santos Celia , Yang Lijuan , Luongo Cindy , Moore Ian N. , Johnson Reed F. , Garza Nicole L. , Zhang Peng , Lusso Paolo , Best Sonja M. , Buchholz Ursula J. , Nouën Cyril Le 
Published: December 2022

ABSTRACTThe pediatric live-attenuated bovine/human parainfluenza virus type 3 (B/HPIV3)-vectored vaccine expressing the prefusion-stabilized SARS-CoV-2 spike (S) protein (B/HPIV3/S-2P) was previously evaluatedin vitroand in hamsters. To improve its immunogenicity, we generated B/HPIV3/S-6P, expressing S further stabilized with 6 proline mutations (S-6P). Intranasal immunization of hamsters with B/HPIV3/S-6P reproducibly elicited significantly higher serum anti-S IgA/IgG titers than B/HPIV3/S-2P; hamster sera efficiently neutralized variants of concern (VoCs), including Omicron variants. B/HPIV3/S-2P and B/HPIV3/S-6P immunization protected hamsters against weight loss and lung inflammation following SARS-CoV-2 challenge with the vaccine-matched strain WA1/2020 or VoCs B.1.1.7/Alpha or B.1.351/Beta and induced near-sterilizing immunity. Three weeks post-challenge, B/HPIV3/S-2P- and B/HPIV3/S-6P-immunized hamsters exhibited a robust anamnestic serum antibody response with increased neutralizing potency to VoCs, including Omicron sublineages. B/HPIV3/S-6P primed for stronger anamnestic antibody responses after challenge with WA1/2020 than B/HPIV3/S-2P. B/HPIV3/S-6P will be evaluated as an intranasal vaccine to protect infants against both HPIV3 and SARS-CoV-2.AUTHOR SUMMARYSARS-CoV-2 infects and causes disease in all age groups. While injectable SARS-CoV-2 vaccines are effective against severe COVID-19, they do not fully prevent SARS-CoV-2 replication and transmission. This study describes the preclinical comparison in hamsters of B/HPIV3/S-2P and B/HPIV3/S-6P, live-attenuated pediatric vector vaccine candidates expressing the “2P” prefusion stabilized version of the SARS-CoV-2 spike protein, or the further-stabilized “6P” version. B/HPIV3/S-6P induced significantly stronger anti-S serum IgA and IgG responses than B/HPIV3/S-2P. A single intranasal immunization with B/HPIV3/S-6P elicited broad systemic antibody responses in hamsters that efficiently neutralized the vaccine-matched isolate as well as variants of concern, including Omicron. B/HPIV3/S-6P immunization induced near-complete airway protection against the vaccine-matched SARS-CoV-2 isolate as well as two variants. Furthermore, following SARS-CoV-2 challenge, immunized hamsters exhibited strong anamnestic serum antibody responses. Based on these data, B/HPIV3/S-6P will be further evaluated in a phase I study.