bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial Calcium Signaling Regulates Branched-Chain Amino Acid Catabolism in Fibrolamellar Carcinoma
Authors: Marsh Nicole M. , MacEwen Melissa J. S. , Chea Jane , Kenerson Heidi L. , Kwong Albert A. , Locke Timothy M. , Miralles Francisco Javier , Sapre Tanmay , Gozali Natasha , Hart Madeleine L. , Bammler Theo K. , MacDonald James W. , Sullivan Lucas B. , Atilla-Gokcumen G. Ekin , Ong Shao-En , Scott John D. , Yeung Raymond S. , Sancak Yasemin 
Published: May 2024

ABSTRACTMetabolic adaptations in response to changes in energy supply and demand are essential for survival. The mitochondrial calcium uniporter plays a key role in coordinating metabolic homeostasis by regulating TCA cycle activation, mitochondrial fatty acid oxidation, and cellular calcium signaling. However, a comprehensive analysis of uniporter-regulated mitochondrial pathways has remained unexplored. Here, we investigate metabolic consequences of uniporter loss- and gain-of-function using uniporter knockout cells and the liver cancer fibrolamellar carcinoma (FLC), which we demonstrate to have elevated mitochondrial calcium levels. Our results reveal that branched-chain amino acid (BCAA) catabolism and the urea cycle are uniporter-regulated metabolic pathways. Reduced uniporter function boosts expression of BCAA catabolism genes, and the urea cycle enzyme ornithine transcarbamylase (OTC). In contrast, high uniporter activity in FLC suppresses their expression. This suppression is mediated by reduced expression of the transcription factor KLF15, a master regulator of liver metabolism. Thus, uniporter responsive calcium signaling plays a central role in FLC-associated metabolic changes, including hyperammonemia. Our study identifies an important role for mitochondrial calcium signaling in metabolic adaptation through transcriptional regulation of metabolism and elucidates its importance for BCAA and ammonia metabolism in FLC.
Researcher and Clinician Preferences for a Journal Transparency Tool: A Mixed-Methods Survey and Focus Group Study
Authors: Ng Jeremy Y. , Liu Henry , Masood Mehvish , Kochhar Jassimar , Moher David , Ehrlich Alan , Iorio Alfonso , Cobey Kelly D. 
Published: May 2024

AbstractBackgroundTransparency within biomedical research is essential for research integrity, credibility, and reproducibility. To increase adherence to optimal scientific practices and enhance transparency, we propose the creation of a journal transparency tool (JTT) that will allow users to obtain information about a given scholarly journal’s operations and transparency policies. This study is part of a program of research to obtain user preferences to inform the proposed JTT. Here, we report on our consultation with clinicians and researchers.MethodsThis mixed-methods study was conducted in two parts. The first part involved a cross-sectional survey conducted on a random sample of authors from biomedical journals. The survey asked clinicians and researchers about the inclusion of a series of potential scholarly metrics and user features in the proposed JTT. Quantitative survey items were summarized with descriptive statistics. Thematic content analysis was employed to analyze text-based responses. Subsequent focus groups used the survey responses to further explore the inclusion of items in the JTT. Items with less than 70% agreement were used to structure discussion points during these sessions. Participants voted on the use of user features and metrics to be considered within the journal tool after each discussion. Thematic content analysis was conducted on interview transcripts to identify the core themes discussed.ResultsA total of 632 participants (5.5% response rate) took part in the survey. A collective total of 74.7% of respondents found it either ‘occasionally, ‘often’, or ‘almost always’ difficult to determine if health information online is based on reliable research evidence.Twenty-two participants took part in the focus groups. Three user features and five journal tool metrics were major discussion points during these sessions. Thematic analysis of interview transcripts resulted in six themes. The use of registration was the only item to not meet the 70% threshold after both the survey and focus groups. Participants demonstrated low scholarly communication literacy when discussing tool metric suggestions.ConclusionsOur findings suggest that the JTT would be valuable for both researchers and clinicians. The outcomes of this research will contribute to developing and refining the tool in accordance with researchers and clinicians.
Implementation of an Enhanced Medication Access Workflow within a Health System Specialty Pharmacy: Impact on Patient & Clinician Experience
Authors: Harkonen Brandon , Cuttitta Anthony , Henderson James , Gavrila Valerie , Mckibbin Jey , Luttman Sherrie , Benedict Wendy , Kelley Lindsey R. , Flanders Scott A. , Choe Hae Mi , Barnes Geoffrey D 
Published: May 2024

ABSTRACTPurposeThe initiation of specialty medications is associated with patient access challenges and clinician burden. This intervention invested resources upstream of the prescription being written. The evaluation assessed the impact on patient and clinician experience.MethodsThe specialty pharmacy intervention was designed to improve medication access within five medical specialty clinics by utilizing an embedded medication access team assigned to patients and prescribers of targeted medications. We used a multi-methods evaluative approach. Semi-structured qualitative interviews provided an understanding of clinician experience. To quantitatively assess associations between the referral process and patient experience, we analyzed the emotional valence of patient portal messages using a retrospective cohort study and an event study framework of a non-randomized, stepped wedge implementation design.ResultsThe intervention was associated with an increase in the net positive emotional valence of patient portal messages (AME, 5.3; 95% CI, 3.8-6.8). Except for gastroenterologists seeing patients for irritable bowel disease, patients cared for in all other specialties experienced statistically significant increases in net positive valence in the primary analysis. Regarding clinician experience, four major interrelated themes emerged from 17 qualitative interviews with prescribers and pharmacists: (1) decreased clinician burden, general praise, (2) improved experience & satisfaction, reduced anxiety & concerns, (3) rewarding praise for other prescribers/colleagues, and (4) excellent coordination, efficiency, and speed.ConclusionInvesting staff resources before, during, and after the prior authorization process greatly improves clinician experience. The positive valence of patient portal messages also increased suggesting patient experience improvements.
Advancing Sewage Sample Surveillance with OmiCrisp: A CRISPR-Based Platform for Variant-Specific SARS-CoV-2 Detection
Authors: Kruthika BS , Roy Bidipta , Shridhar Varsha , Gupta Vaijayanti , Chandru Vijay , Arora Reety 
Published: May 2024

AbstractThe detection and differentiation of SARS-CoV-2 variants are vital for disease management and timely patient isolation. Although qRT-PCR has been the standard method, our OmiCrisp assay has shown superior results in identifying Omicron and non-Omicron variants. The World Health Organization advises ongoing sewage surveillance to monitor community viral load, accounting for both symptomatic and asymptomatic individuals. In a previous study, our CRISPR-based assay achieved a 99% concordance with qRT-PCR in sewage samples. We expanded this research by analyzing 182 sewage samples from Bangalore during the JN.1 (BA.2.86.1.1) variant outbreak. Using the OmiCrisp assay, 153 samples (84.06%) tested positive, 16 (8.79%) were negative, and 13 (7.14%) were low positive. Results indicated a significant reduction in positivity rates by the end of the study. The OmiCrisp assay thus proves to be an accurate and effective tool for community-wide surveillance of SARS-CoV-2 variants.
The Longevity Landscape: Value Creation for Healthy Aging
Authors: Mekniran Wasu , Giger Odile-Florence , Fleisch Elgar , Kowatsch Tobias , Jovanova Mia 
Published: May 2024

ABSTRACTBackgroundThe global aging population underscores a critical need to tackle accompanying health and economic challenges, at all levels of society. ThisAll-of-Societyapproach emphasizes the involvement of various stakeholders—governments, NGOs, researcher centers, private companies, local communities, and opinion leaders—to collectively promote healthy aging. However, how stakeholders enable healthy longevity remains unclear.ObjectiveThis study examines how global stakeholders (governments, NGOs, researcher centers, private companies, local communities, and opinion leaders) create value towards healthy longevity. We identify the healthy longevity dimension of stakeholders’ value propositions and examine alignment between their propositions as an indicator of shared goals.MethodsFollowing theAll-of-Societyapproach, we analyzed the healthy longevity aspects of value propositions among the six classes of stakeholders (N=128). We (1) employed semantic topic modeling to identify the primary value proposition topics as related to healthy longevity and (2) computed proposition alignment using similarity networks.ResultsOur analysis revealed varying degrees of alignment between stakeholders’ healthy longevity propositions, with the lowest alignment observed for local communities and researcher centers.ConclusionsFindings underscore a key need to strengthen synergies between academic and community-based initiatives to promote translational science and highlight opportunities for strategic partnerships in the evolving healthy longevity field.What is already known on this topicThe National Academy of Medicine’sAll-of-Societyapproach advocates for multi-stakeholder engagement towards healthy longevity, but specific stakeholder contributions, and their alignment toward shared goals, are poorly understood.What this study addsTo our knowledge, this study is the first to provide empirical evidence into the value propositions of healthy longevity stakeholders on a societal scale. It highlights key areas where multi-stakeholder collaboration can be strengthened—particularly between academic and local community initiatives—and proposes five strategies to strengthen collaboration.How this study might affect research, practice, or policyPrioritizing (1) community-based participatory research, (2) translating healthy aging-related research findings into accessible resources, (3) prioritizing equity in intervention delivery, (4) establishing community advisory boards, and (5) developing knowledge translation and training programs, could potentially better align academic and community efforts towards more aligned, equitable and effective healthy longevity initiatives.
Enhancing the Diagnostic Utility of ASL Imaging in Temporal Lobe Epilepsy through FlowGAN: An ASL to PET Image Translation Framework
Authors: Lucas Alfredo , Vadali Chetan , Mouchtaris Sofia , Arnold T. Campbell , Gugger James J. , Kulick-Soper Catherine , Josyula Mariam , Petillo Nina , Das Sandhitsu , Dubroff Jacob , Detre John A. , Stein Joel M. , Davis Kathryn A. 
Published: May 2024

Background and SignificancePositron Emission Tomography (PET) using fluorodeoxyglucose (FDG-PET) is a standard imaging modality for detecting areas of hypometabolism associated with the seizure onset zone (SOZ) in temporal lobe epilepsy (TLE). However, FDG-PET is costly and involves the use of a radioactive tracer. Arterial Spin Labeling (ASL) offers an MRI-based quantification of cerebral blood flow (CBF) that could also help localize the SOZ, but its performance in doing so, relative to FDG-PET, is limited. In this study, we seek to improve ASL’s diagnostic performance by developing a deep learning framework for synthesizing FDG-PET-like images from ASL and structural MRI inputs.MethodsWe included 68 epilepsy patients, out of which 36 had well lateralized TLE. We compared the coupling between FDG-PET and ASL CBF values in different brain regions, as well as the asymmetry of these values across the brain. We additionally assessed each modality’s ability to lateralize the SOZ across brain regions. Using our paired PET-ASL data, we developed FlowGAN, a generative adversarial neural network (GAN) that synthesizes PET-like images from ASL and T1-weighted MRI inputs. We tested our synthetic PET images against the actual PET images of subjects to assess their ability to reproduce clinically meaningful hypometabolism and asymmetries in TLE.ResultsWe found variable coupling between PET and ASL CBF values across brain regions. PET and ASL had high coupling in neocortical temporal and frontal brain regions (Spearman’sr >0.30, p < 0.05) but low coupling in mesial temporal structures (Spearman’sr <0.30, p > 0.05). Both whole brain PET and ASL CBF asymmetry values provided good separability between left and right TLE subjects, but PET (AUC = 0.96, 95% CI: [0.88, 1.00]) outperformed ASL (AUC = 0.81; 95% CI: [0.65, 0.96]). FlowGAN-generated images demonstrated high structural similarity to actual PET images (SSIM = 0.85). Globally, asymmetry values were better correlated between synthetic PET and original PET than between ASL CBF and original PET, with a mean correlation increase of 0.15 (95% CI: [0.07, 0.24],p<0.001, Cohen’sd= 0.91). Furthermore, regions that had poor ASL-PET correlation (e.g. mesial temporal structures) showed the greatest improvement with synthetic PET images.ConclusionsFlowGAN improves ASL’s diagnostic performance, generating synthetic PET images that closely mimic actual FDG-PET in depicting hypometabolism associated with TLE. This approach could improve non-invasive SOZ localization, offering a promising tool for epilepsy presurgical assessment. It potentially broadens the applicability of ASL in clinical practice and could reduce reliance on FDG-PET for epilepsy and other neurological disorders.
High acceptability of newborn screening for sickle cell disease among post-natal mothers in western Kenya
Authors: Orimbo John , Awandu Shehu Shagari , Muhonja Faith , Owili Patrick , Omondi Dickens 
Published: May 2024

AbstractBackgroundSickle cell disease is a genetically inherited blood disorder that manifests early in life with resultant significant health complications. Globally, nearly three quarters of all affected babies are in sub-Saharan Africa. Early identification of babies with sickle cell disease through newborn screening followed by early linkage to care is recommended. However, the program has not been widely adopted in the sub-Saharan Africa. Evidence on acceptability of newborn screening to scale up newborn screening program is scarce. This study assessed factors associated with acceptability of newborn screening among mothers of newborns delivered at Homa Bay county teaching and referral hospital, western Kenya.MethodsThis study employed a cross-sectional design among postnatal mothers at Homa Bay county teaching and referral hospital with 399 postnatal mothers enrolled into the study. A semi-structured questionnaire was used for data collection. Maternal sociodemographic characteristics, knowledge, and perception were assessed. Babies were also screened for sickle cell disease using Sickle SCAN point-of-care test. The acceptability was calculated as percentage of mothers accepting to have their babies screened. Data were analyzed using logistic regression to explore factors associated with acceptability of newborn screening for sickle cell disease.ResultsNinety-four percent of mothers accepted newborn screening for sickle cell disease. Mother’s age and occupation were significantly associated with acceptability of newborn screening for sickle cell disease. Younger mothers (OR=3.01;95%CI=1.16-7.83;p=0.024) and being a student (OR= 6.18; 95%CI= 1.18-32.22;p=0.031) were significant at bivariate regression analysis. Only being a student (aOR= 25.02; 95% CI=1.29-484.51; p= 0.033) was significant at multivariate logistic regression analysis.ConclusionThe acceptability of newborn screening for sickle cell disease is high in the county. The Homabay county and the Kenyan ministry of health should implement routine newborn screening for sickle cell disease in all level 2-6 hospitals.
Impact of Dental Disorders on Self-rated dental Health Status of the Elderly in Selected Rural Communities in Kenya
Authors: Amulla Walter Ogutu , Njororai Fletcher 
Published: May 2024

AbstractLow prioritization of oral care for the elderly and inadequacy of resources results in high prevalence of dental disorders in this population in most African countries. This study aimed at assessing the impact of self-rated dental health among the elderly in Kenya. A cross-sectional quantitative study was conducted among 300 subjects in parts of Karachuonyo sub-county of Homa Bay County, Kenya. The sample size was determined using Yamane’s formula based on a study population of 1159. Data was collected through interviewer-administered questionnaires. Majority (64%) of the respondents were aged 65-74 years. Female respondents were more (55.3%) than males (44.75). Further, 8 in 10 of the study sample never had any formal employment with nearly the same proportion (79.3%) self-rating their economic status as poor. Nearly 7 out of 10 (67%) respondents had lost at least one tooth due to medical extraction whereas half of the respondents (52.3%) were having at least one carious tooth at the time of data collection. Tooth loss had the strongest impact on self-rated dental health (X2=27.818, p<0.00001, φ = 0.305) followed by tooth mobility (X2=27.180,p<0.00001, φ = 0.301), gingival bleeding (X2=19.378, p=0.000011, φ = 0.254) and cavities (X2=17.757, p=0.000025, φ = 0.243). The study established that dental disorders significantly but disproportionately impacted self-rated dental health of the elderly, with tooth loss being the leading disorder. Increasing provision of services for the elderly for dental health needs is critical in Kenya as in most African countries.
Longitudinal Influenza A Virus Screening of Retail Milk from Canadian Provinces (Rolling Updates)
Authors: Wallace Hannah L. , Wight Jordan , Baz Mariana , Dowding Barbara , Flamand Louis , Hobman Tom , Jean Francois , Joy Jeffrey B , Lang Andrew S. , MacParland Sonya , McCormick Craig , Noyce Ryan , Russell Rodney S. , Sagan Selena M. , Snyman Jumari , Rzeszutek Gabriela J. , Jafri Mustafa S. , Bogoch Isaac , Kindrachuk Jason , Rasmussen Angela L. 
Published: May 2024

AbstractHighly pathogenic avian influenza (HPAI) H5N1 has caused the deaths of more than 100 million birds since 2021, and human cases since 1997 have been associated with significant morbidity and mortality. Given the recent detection of HPAI H5N1 in dairy cattle and H5N1 RNA detections in pasteurized retail milk in the United States, we established the Pan-Canadian Milk (PCM) Network. Through our network of collaborators from across Canada, retail milk is being procured longitudinally and sent to a central laboratory for testing for the presence of influenza A virus RNA. To date (05 July 2024), we have tested 92 retail milk samples from all ten Canadian provinces (NL, NS, PEI, NB, QC, ON, MB, SK, AB, and BC) and all have tested negative for influenza A virus RNA. Testing is ongoing and these results will be updated on rolling basis as additional data becomes available. Despite no known HPAI infections of dairy cattle in Canada to date, H5N1 poses a significant threat to the health of both humans and other animals. Routine surveillance of retail milk on a national scale will allow for monitoring of infected dairy cattle on an ongoing basis in a cost-effective, standardized, scalable and easily accessible manner. Our network and testing will act as an early detection system to help inform containment and mitigation activities if positive samples are identified.
Utility of cerebrovascular imaging biomarkers to detect cerebral amyloidosis
Authors: Howe Matthew D. , Caruso Megan R. , Manoochehri Masood , Kunicki Zachary J. , Emrani Sheina , Rudolph James L. , Huey Edward D. , Salloway Stephen P. , Oh Hwamee ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: May 2024

STRUCTURED ABSTRACTINTRODUCTIONThe relationship between cerebrovascular disease (CVD) and amyloid-β (Aβ) in Alzheimer disease (AD) is understudied. We hypothesized that magnetic resonance imaging (MRI)-based CVD biomarkers, including cerebral microbleeds (CMBs), ischemic infarction, and white matter hyperintensities (WMH), would correlate with Aβ positivity on positron emission tomography (Aβ-PET).METHODSWe cross-sectionally analyzed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI, N=1,352). Logistic regression was used to calculate odds ratios (ORs), with Aβ-PET positivity as the standard-of-truth.RESULTSFollowing adjustment, WMH (OR=1.25) and superficial CMBs (OR=1.45) remained positively associated with Aβ-PET positivity (p<.001). Deep CMBs and infarcts exhibited a varied relationship with Aβ-PET in cognitive subgroups. The combined diagnostic model, which included CVD biomarkers and other accessible measures, significantly predicted Aβ-PET (pseudo-R2=.41).DISCUSSIONThe study highlights the translational value of CVD biomarkers in diagnosing AD, and underscores the need for more research on their inclusion in diagnostic criteria.ClinicalTrials.gov:ADNI-2 (NCT01231971), ADNI-3 (NCT02854033)
Mobility and non-household environments: understanding dengue transmission patterns in urban contexts
Authors: Peña-García Víctor Hugo , Ndenga Bryson A. , Mutuku Francis M. , Bisanzio Donal , LaBeaud A. Desiree , Mordecai Erin A. 
Published: May 2024

AbstractBackgroundHouseholds (HH) have been traditionally described as the main environments where people are at risk of dengue (and other arbovirus) infection. Mounting entomological evidence has suggested a larger role of environments other than HH in transmission. Recently, an agent-based model (ABM) estimated that over half of infections occur in non-household (NH) environments like workplaces, markets, and recreational sites. However, the importance of human and vector mobility and the configurations of urban spaces in mediating the effects of NH on dengue transmission remains understudied.MethodsTo improve our knowledge of the relevance of NH in transmission, we expanded an ABM calibrated from field data in Kenya to examine movement of people and vectors under different spatial configurations of buildings. In this model, we assessed the number of people traveling between HH and NH and their distance. Those were studied on three different urban configurations, on which the NH are spatially distributed either randomly (scattered), centered (in a single center), or clustered (in more than one cluster).ResultsAcross simulations, the number of people moving is a major influential variable where higher levels of movement between HH and NH increases the number of cases. In addition, the number of cases is higher when NH are scattered. Intriguingly, the distance that people travel from HH to NH seems to have little effect on dengue burden; however, it affects the level of spatial clustering of cases.ConclusionsThese results highlight the importance of NH as a major spreader of infections between HH and NH environments supporting the relevance of NH in transmission and its interaction with human movement in driving dengue dynamics.