bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lives and Livelihood, Not Quite a Trade-Off: A Cross-Country Analysis of the Short-Term Impact of COVID-19 Mortality on Real GDP
Authors: Suah Jing Lian 
Published: February 2023

AbstractIntroductionA supposed lives-livelihood trade-off (LLTO) has been at the centre stage of the COVID-19 pandemic, where policymakers often attempt to balance the health cost of COVID-19, including deaths, and the economic cost of lockdowns.MethodologyThis paper uses country-level panel (longitudinal) data on real GDP, stringency of non-pharmaceutical interventions (NPIs), economic policy support, COVID-19 deaths, and vaccination to quantify the short-run LLTO. Beyond descriptive analysis, adjustments were made — (1) two-stage least squares instrumental variables in a cross-sectional setting using pre-pandemic institutional quality as the excluded instrument, and (2) two-way fixed effects in a panel data setting.FindingsReal GDP is negatively associated with COVID-19 deaths, as does more stringent containment measures. However, the offsetting positive association of real GDP with economic policy support is substantial. A historical decomposition of average real GDP that the positive attribution of fiscal support roughly equates the negative attribution of lockdown stringency and COVID-19 mortality.ConclusionCross-country empirical evidence suggests no direct tradeoff between the economy, and public health. A change in policy thinking from a LLTO paradigm to a ‘no trade-off’ entails economic policy treating public health goals as invariant in supporting incomes through adequate, direct, and timely means.
Altered glutamate signaling in Parkinson’s disease patients with REM sleep behavior disorder
Authors: Doppler Christopher E.J. , Seger Aline , Farrher Ezequiel , Brambilla Cláudia Régio , Hensel Lukas , Filss Christian P. , Gogishvili Ana , Shah N. Jon , Lerche Christoph W. , Neumaier Bernd , Langen Karl-Josef , Fink Gereon R. , Sommerauer Michael 
Published: February 2023

AbstractBackground and ObjectivesClinical heterogeneity of patients with Parkinson’s disease is well recognized. Parkinson’s disease with rapid eye movement (REM) sleep behavior disorder (RBD) is a more malignant phenotype with faster motor progression and higher non-motor symptom burden. However, the neural mechanisms underlying this clinical divergence concerning disbalances in neurotransmitter systems remain elusive.MethodsCombining magnetic resonance (MR) spectroscopy and11C-ABP688 positron emission tomography (PET) on PET/MR hybrid system, we simultaneously investigated two different mechanisms of glutamate signaling in patients with Parkinson’s disease. Thirty-three patients were grouped according to their RBD status in overnight video-polysomnography and compared to 15 age- and sex-matched healthy control (HC) subjects. Total volumes of distribution (VT) of11C-ABP688 were estimated with metabolite-corrected plasma concentrations during steady-state conditions between minutes 45 to 60 of the scan following a bolus-infusion protocol. Glutamate, glutamine, and glutathione levels were investigated with single voxel STEAM MR spectroscopy of the left putamen.ResultsWe measured globally elevated VTof11C-ABP688 in patients with Parkinson’s disease and RBD compared to patients without RBD and HC subjects (F(2,45) = 5.579,p= 0.007). Conversely, glutamatergic metabolites did not differ between groups and did not correlate with the regional VTof11C-ABP688. VTof11C-ABP688 correlated with the amount of REM sleep without atonia (F(1,42) = 5.600,p= 0.023), and with dopaminergic treatment response in Parkinson’s disease patients (F(1,30) = 5.823,p= 0.022).ConclusionOur results suggest that patients with Parkinson’s disease and RBD exhibit altered glutamatergic signaling indicated by higher VTof11C-ABP688 despite unaffected glutamate metabolism. The disbalance of glutamate receptors and neurotransmitter might indicate a novel mechanism contributing to the heterogeneity of Parkinson’s disease and warrants further investigation of drugs targeting mGluR5.
Mapping Sleep’s Oscillatory Events as a Biomarker of Alzheimer’s Disease
Authors: Pulver Rachelle L. , Kronberg Eugene , Medenblik Lindsey M. , Kheyfets Vitaly O. , Ramos Alberto R. , Holtzman David M. , Morris John C. , Toedebusch Cristina D. , Sillau Stefan H. , Bettcher Brianne M. , Lucey Brendan P. , McConnell Brice V. 
Published: February 2023

AbstractObjectiveMemory-associated neural circuits produce oscillatory events within single-channel sleep electroencephalography (EEG), including theta bursts (TBs), sleep spindles (SPs) and multiple subtypes of slow waves (SWs). Changes in the temporal “coupling” of these events are proposed to serve as a biomarker for early stages of Alzheimer’s disease (AD) pathogenesis.MethodsWe analyzed data from 205 aging adults, including single-channel sleep EEG, cerebrospinal fluid (CSF) AD-associated biomarkers, and Clinical Dementia Rating® (CDR®) scale. Individual SW events were sorted into high and low transition frequencies (TF) subtypes. We utilized time-frequency spectrogram locations within sleep EEG to “map” the precision of SW-TB and SW-SP neural circuit coupling in relation to amyloid positivity (by CSF Aβ42/Aβ40threshold), cognitive impairment (by CDR), and CSF levels of AD-associated biomarkers.ResultsCognitive impairment was associated with lower TB spectral power in both high and low TF SW-TB coupling (p<0.001, p=0.001). Cognitively unimpaired, amyloid positive aging adults demonstrated lower precision of the neural circuits propagating high TF SW-TB (p<0.05) and low TF SW-SP (p<0.005) event coupling, compared to cognitively unimpaired amyloid negative individuals. Biomarker correlations were significant for high TF SW-TB coupling with CSF Aβ42/Aβ40(p=0.005), phosphorylated-tau181(p<0.005), and total-tau (p<0.05). Low TF SW-SP coupling was also correlated with CSF Aβ42/Aβ40(p<0.01).InterpretationLoss of integrity in neural circuits underlying sleep-dependent memory processing can be measured for both SW-TB and SW-SP coupling in spectral time-frequency space. Breakdown of sleep’s memory circuit integrity is associated with amyloid positivity, higher levels of AD-associated pathology, and cognitive impairment.
BCM PDX Portal: An Intuitive Web-based Tool for Patient-Derived Xenograft Collection Management, as well as Visual Integration of Clinical and Omics Data
Authors: Dowst Heidi , McOwiti Apollo , Zheng Fei , Rajaram Srinivasan Ramakrishnan , Hernandez-Herrera Anadulce , Rainusso Nino , Brubaker Lisa , Yao Qizhi Cathy , Redell Michelle , Stevens Alexandra , Lerner Seth , Woodfield Sarah , Espinoza Andres F. , Landua John D. , Hilsenbeck Susan G. , Dobrolecki Lacey E. , Lewis Michael T. 
Published: February 2023

ABSTRACTObjectiveMouse Patient-Derived Xenograft (PDX) models are essential tools for evaluating experimental therapeutics. Baylor College of Medicine (BCM) established a PDX Core to provide technical support and infrastructure for PDX-based research. To manage PDX collections effectively, de-identified patient clinical and omics data, as well as PDX-related information and omics data, must be curated and stored. Data must then be analyzed and visualized for each case. To enhance PDX collection management and data dissemination, the BCM Biomedical Informatics Core created the BCM PDX Portal (https://pdxportal.research.bcm.edu/).Materials and MethodsPatient clinical data are abstracted from medical records for each PDX and stored in a central database. Annotations are reviewed by a clinician and de-identified. PDX development method and biomarker expression are annotated. DNAseq, RNAseq, and proteomics data are processed through standardized pipelines and stored. PDX gene expression (mRNA/protein), copy number alterations, and mutations can be searched in combination with clinical markers to identify models potentially useful as a PDX cohort.ResultsPDX collection management and PDX selection of models for drug evaluation are facilitated using the PDX Portal.DiscussionTo improve the translational effectiveness of PDX models, it is beneficial to use a tool that captures and displays multiple features of the patient clinical and molecular data. Selection of models for studies should be representative of the patient cohort from which they originated.ConclusionThe BCM PDX Portal is a highly effective PDX collection management tool allowing data access in a visual, intuitive manner thereby enhancing the utility of PDX collections.
Changes of sociobehavioural characteristics and HIV in 29 Sub-Saharan African countries, 2000-2018
Authors: Post Jeffrey , Ng’ambi Wingston , Keiser Olivia , Merzouki Aziza 
Published: February 2023

AbstractIntroductionHIV epidemics and associated sociobehavioural characteristics vary widely across Sub-Saharan African (SSA) countries. In this study, we investigated how national changes on sociobehavioural characteristics may be associated with trajectories in HIV epidemics.MethodsWe analyzed aggregated data from 80 DHS surveys of 29 SSA countries between 2000 and 2018. We described each national survey by 46 pre-selected demographic, socio- economic, behavioural and HIV-related variables. Using Principal Component Analysis, we reduced the dimensionality of surveys and visualized them on a 2-dimensional space. We used consensus clustering to identify groups of countries with similar sociobehavioural characteristics over time, and identified the main drivers of change. We used k-means clustering with dynamic time warping to group countries based on the evolution of their national HIV effective contact rates since 1990 (computed based on UNAIDS estimates of yearly HIV incidence and prevalence).ResultsWe identified three groups of countries with similar sociobehavioural and HIV-related characteristics that persisted from 2000 to 2018. While countries within groups remained similar since 2000, differences between the groups increased over time. The most important characteristics that explained the change in the sociobehavioural space since 2000 were: ART coverage, HIV testing, increase in accepting attitudes towards People Living with HIV/AIDS and increasing knowledge about AIDS. We also identified two groups of countries with characteristic evolutions of HIV effective contact rates since 1990. The first group of countries was characterized by a rapid decrease of effective contact rate since the early 1990. The second group experienced a slow decrease of the effective contact rate in the early 1990, followed by a faster decrease after 1995. While the three clusters based on sociobehavioural characteristics were associated with different peak levels of HIV incidence, the two clusters based on the progression of the effective contact rate were associated with the timing when peak HIV incidence levels were reached.ConclusionsOur findings suggest that the initial conditions of nascent epidemics, likely determined by sociobehavioural characteristics, are crucial in determining the long-term progression of HIV epidemics. Our methods can help to predict the effects of behavioural change on the HIV epidemic and design targeted interventions to reach epidemic control.
“We had to put ourselves in their shoes”: Experiences of Medical Students and ObGyn Residents with a Values Clarification Workshop on Abortion
Authors: Valley Taryn M. , Cowley Elise S. , Farooque Alma , Shultz Zoey B. , Williams Margaret , Askins Jacquelyn , Godecker Amy , Jacques Laura 
Published: February 2023

AbstractPurposeValues clarification workshops on abortion have been shown to increase support for abortion among healthcare workers. However, few studies have examined the impact of values clarification workshops on abortion among medical trainees. This study aimed to understand medical student and obstetrics and gynecology (ObGyn) residents’ experiences with a virtual values clarification workshop on abortion.MethodsClerkship year medical students and ObGyn residents at four midwestern teaching hospitals were invited to be interviewed about their experiences in a virtual values clarification workshop on abortion from January 2021 through December 2021. A single interviewer conducted interviews via Zoom using a standardized interview guide. Participants were asked to provide feedback and discuss their experiences in the workshop. Four qualitatively trained evaluators coded the interview transcripts in NVivo, using an inductive approach to establish consensus codes then themes.ResultsThis study interviewed 37 trainees, including 24 medical students and 13 ObGyn residents, as well as five facilitators, between November 2021 and February 2022. Three themes emerged in both trainee groups. First, participants found the workshopshelped trainees clarify and understand their own views on abortionthrough thought exploration, peer validation, and reflection on their views’ potential societal impacts. Second, through the workshop,participants reflected on others’ opinions on abortionand better understood the spectrum of beliefs their peers held. Finally, participants found the workshopshelped them explore and develop their professional identity as physicians-in-training, through practicing communication skills and building trust and mutual respect among peers.ConclusionsMedical trainees found values clarification workshops on abortion to be valuable, helping them establish their own beliefs about abortion, contextualize these beliefs among their peers’, and practice professionalism. These findings indicate that values clarification workshops can play a key role in helping medical trainees discuss abortion and prepare for their professional future.One in four people capable of pregnancy will have an abortion during their lifetime; abortions are one of the most common medical procedures in the United States1. Given this ubiquity, abortion education is recommended for medical students and required for Obstetrics and Gynecology (ObGyn) residents2–4. However, abortion education is increasingly sparse for both groups of trainees5,6. In addition, abortion is highly stigmatized and polarizing, including within healthcare7–9.
Development and evaluation of a novel educational program for providers on the use of polygenic risk scores
Authors: Yanes T. , Wallingford C. , Young MA. , McInerney-Leo A.M. , Willis A. , McKnight L. , Terrill B. , McInerny S. , Forrest L. , Cicciarelli L. , Williams R. , Keane H. , James PA 
Published: February 2023

AbstractBackgroundPolygenic risk scores (PRS) for breast and ovarian cancer risk are increasingly available to the public through clinical research and commercial genetic testing companies. Healthcare providers frequently report limited knowledge and confidence using PRS, representing a significant barrier to evaluation and uptake of this technology. We aimed to develop and evaluate the impact of a novel online educational program on genetic healthcare providers (GHP) attitudes, confidence and knowledge using PRS for breast and ovarian cancer risk.MethodsThe educational program was informed by adult learning theory and the Kolb experiential learning model. The program was comprised of two phases: i) an online module covering the theoretical aspects of PRS and ii) a facilitated virtual workshop with pre-recorded role plays and case discussions. A pre-and post-education survey was administered to evaluate the impact of the educational program on GHP attitudes, confidence, knowledge, and preparedness for using PRS. Eligible participants were GHP working in one of 12 familial cancer in Australia registered to recruit patients for a breast and ovarian cancer PRS clinical trial and completed the education program.Results124 GHP completed the PRS education, of whom 80 (64%) and 67 (41%) completed the pre- and post-evaluation survey, respectively. Pre-education, GHP reported limited experience, confidence and preparedness using PRS. GHP frequently recognized potential benefits to PRS, most commonly that this information could improve access to tailored screening (rated as beneficial/very beneficial by 92% of GHP pre-education). Completion of the education program was associated with significantly improved attitudes (p=<0.001), confidence (p=<0.001), knowledge of (p=<0.001) and preparedness (p=<0.001) using PRS. Most GHP indicated the education program entirely met their learning needs (73%) and felt the content was entirely relevant to their clinical practice (88%). GHP identified further PRS implementation issues including limited funding models, diversity issues, need for clinical guidelines and ongoing updates given the rapid pace of PRS research.ConclusionsDelivery of a novel education program can improve GHP attitudes, confidence, knowledge, and preparedness using PRS. Careful consideration of healthcare providers’ learning needs is required to support PRS research and clinical translation.
Prediction and Design of Protease Enzyme Specificity Using a Structure-Aware Graph Convolutional Network
Authors: Lu Changpeng , Lubin Joseph H. , Sarma Vidur V. , Stentz Samuel Z. , Wang Guanyang , Wang Sijian , Khare Sagar D. 
Published: February 2023

AbstractSite-specific proteolysis by the enzymatic cleavage of small linear sequence motifs is a key post-translational modification involved in physiology and disease. The ability to robustly and rapidly predict protease substrate specificity would also enable targeted proteolytic cleavage – editing – of a target protein by designed proteases. Current methods for predicting protease specificity are limited to sequence pattern recognition in experimentally-derived cleavage data obtained for libraries of potential substrates and generated separately for each protease variant. We reasoned that a more semantically rich and robust model of protease specificity could be developed by incorporating the three-dimensional structure and energetics of molecular interactions between protease and substrates into machine learning workflows. We present Protein Graph Convolutional Network (PGCN), which develops a physically-grounded, structure-based molecular interaction graph representation that describes molecular topology and interaction energetics to predict enzyme specificity. We show that PGCN accurately predicts the specificity landscapes of several variants of two model proteases: the NS3/4 protease from the Hepatitis C virus (HCV) and the Tobacco Etch Virus (TEV) proteases. Node and edge ablation tests identified key graph elements for specificity prediction, some of which are consistent with known biochemical constraints for protease:substrate recognition. We used a pre-trained PGCN model to guide the design of TEV protease libraries for cleaving two non-canonical substrates, and found good agreement with experimental cleavage results. Importantly, the model can accurately assess designs featuring diversity at positions not present in the training data. The described methodology should enable the structure-based prediction of specificity landscapes of a wide variety of proteases and the construction of tailor-made protease editors for site-selectively and irreversibly modifying chosen target proteins.
Functional organization of visual responses in the octopus optic lobe
Authors: Pungor Judit R. , Allen V. Angelique , Songco-Casey Jeremea O. , Niell Cristopher M. 
Published: February 2023

SummaryCephalopods are highly visual animals with camera-type eyes, large brains, and a rich repertoire of visually guided behaviors. However, the cephalopod brain evolved independently from that of other highly visual species, such as vertebrates, and therefore the neural circuits that process sensory information are profoundly different. It is largely unknown how their powerful but unique visual system functions, since there have been no direct neural measurements of visual responses in the cephalopod brain. In this study, we used two-photon calcium imaging to record visually evoked responses in the primary visual processing center of the octopus central brain, the optic lobe, to determine how basic features of the visual scene are represented and organized. We found spatially localized receptive fields for light (ON) and dark (OFF) stimuli, which were retinotopically organized across the optic lobe, demonstrating a hallmark of visual system organization shared across many species. Examination of these responses revealed transformations of the visual representation across the layers of the optic lobe, including the emergence of the OFF pathway and increased size selectivity. We also identified asymmetries in the spatial processing of ON and OFF stimuli, which suggest unique circuit mechanisms for form processing that may have evolved to suit the specific demands of processing an underwater visual scene. This study provides insight into the neural processing and functional organization of the octopus visual system, highlighting both shared and unique aspects, and lays a foundation for future studies of the neural circuits that mediate visual processing and behavior in cephalopods.HighlightsThe functional organization and visual response properties of the cephalopod visual system are largely unknownUsing calcium imaging, we performed mapping of visual responses in the octopus optic lobeVisual responses demonstrate localized ON and OFF receptive fields with retinotopic organizationON/OFF pathways and size selectivity emerge across layers of the optic lobe and have distinct properties relative to other species
Hemi Manganese Exchangers 1 and 2 enable manganese import at the plasma membrane in cyanobacteria
Authors: Reis Mara , Brandenburg Fabian , Knopp Michael , Flachbart Samantha , Bräutigam Andrea , Metzger Sabine , Gould Sven B. , Eisenhut Marion 
Published: February 2023

ABSTRACTManganese (Mn) is key to oxygenic photosynthesis as it catalyzes the splitting of water in photosystem II and functions as cofactor of multiple enzymes. A single ABC-type transporter, MntCAB, is so far established for the uptake of the metal under limiting conditions in cyanobacteria. It is unknown how Mn is imported under replete conditions. We identified two proteins in the cyanobacteriumSynechocystissp. PCC 6803, which are homologous to the unknown protein family 0016 (UPF0016) member manganese exporter (Mnx). In contrast to Mnx, which consists of six transmembrane domains, the new candidate proteins contain three transmembrane domains. Hence, we named them hemi manganese exchangers (Hmx) 1 and 2. Knock-out mutants inhmx1and/orhmx2showed sensitivity toward low Mn supplementation, and reduced intracellular Mn pools. Additional deletion ofmntChindered the cells to thrive unless the medium was supplemented with Mn to compensate for the depletion of their intracellular Mn pool. In accordance with the observed localization of Hmx1 and Hmx2 in the plasma membrane, we postulate a Mn uptake function for heteromeric Hmx1/2 across the plasma membrane under a wide range of Mn concentrations and a supporting role for the MntCAB system under Mn-limiting conditions. On the basis of their phylogenies, we propose that Hmx1 and Hmx2 are the ancestral progenitors of eukaryote-type UPF0016 proteins with six transmembrane domains. The Mn transport function of Hmx1/2 underscores this as a fundamental and ancient feature of the UPF0016 family. Potentially, Hmx1 and Hmx2 coevolved with the internalization of the oxygen-evolving complex.