bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Integration of Health Equity into Policy to Reduce Disparities: Lessons from California during the COVID-19 Pandemic
Authors: Kwan Ada T. , Vargo Jason , Kurtz Caroline , Panditrao Mayuri , Hoover Christopher M. , León Tomás M. , Rocha David , Wheeler William , Jain Seema , Pan Erica S. , Shete Priya B. 
Published: June 2024

AbstractRacial and ethnic minoritized groups and socioeconomically disadvantaged communities experience longstanding health-related disparities in the US and were disproportionately affected throughout the COVID-19 pandemic. How departments of public health can explicitly address these disparities and their underlying determinants remains less understood. To inform future public health responses, this paper details how California strategically placed health equity at the core of its COVID-19 reopening and response policy, known as theBlueprint for a Safer Economy. In effect from August 2020 to June 2021, “the Blueprint” employed the use of the California Healthy Places Index (HPI), a summary measure of 25 social determinants of health constructed at the census tract level, to guide activities. Using California’s approach, we categorized the state population by HPI quartiles at the state and within-county levels (HPIQ1 representing the least advantaged, HPIQ4, the most advantaged) from HPI data available to demonstrate how the state monitored COVID-19 test, case, mortality, and vaccine outcomes using equity metrics developed for the Blueprint. Notable patterns emerged. Testing disparities disappeared during the summer and winter surges but resurfaced between surges. Monthly case rate ratios (RR) peaked in May 2020 for HPIQ1 compared to HPIQ4 (RR 6.61, 95%CI: 6.41–6.81), followed by mortality RR peaking in June 2020 (RR 5.06, 95% CI: 4.34–5.91). As the pandemic wore on, case and mortality disparities between lower HPI quartiles relative to HPIQ4 reduced but remained. Utilizing an ABSM, such as HPI, enabled a data-driven approach to identify priority communities, allocate resources, and monitor outcomes based on need during a large-scale public health emergency.
Normative characterization of age-related periodic and aperiodic activity in resting-state clinical EEG recordings
Authors: Leroy Sophie , Bublitz Viktor , von Dincklage Falk , Antonenko Daria , Fleischmann Robert 
Published: June 2024

AbstractObjectiveNon-invasive oscillatory brain stimulation techniques target the oscillatory activity of the brain and have several potential therapeutic applications in the clinical context. The aim of these analyses from clinical routine EEG recordings was to provide normative values of physiological age-related oscillatory (periodic) and non-rhythmic (aperiodic) activity.MethodsWe analyzed 532 EEGs of patients between 8 and 92 years of age. EEG segments were preprocessed, and the power spectrum was computed using a multitaper method. We decomposed the power spectrum into periodic (peak power, frequency, and bandwidth) and aperiodic (intercept and exponent) components. Linear regression models were used to investigate age-related changes in these parameters.ResultsWe observed significant global age-related changes in the periodic alpha (- 0.015 Hz/year) and gamma (+ 0.013 to + 0.031Hz/year) peak frequency as well as in the aperiodic exponent (- 0.003 to - 0.004 μV2/Hz/year). In the other parameters there were solely regional or no significant age-related changes.ConclusionsDecomposing the power spectrum into periodic and aperiodic components allows for the characterization of age-related changes.SignificanceThis study provides the first spectrum-wide normative characterization of age-related changes in periodic and aperiodic activity, relevant for non-invasive brain stimulation with alternating current targeting ongoing oscillatory activity.Highlights-Alpha peak frequency decreases with age, while gamma peak frequency accelerates.-Age-related changes in alpha and theta power result from a flattening of the aperiodic slope, not decreased oscillatory activity-Decomposing the EEG spectrum into periodic and aperiodic activity is essential when characterizing ongoing oscillatory activity
The resilient brain against childhood poverty
Authors: Hu Bowen , Yang Tongxi , Hu Yuanyuan , Qin Shaozheng 
Published: June 2024

AbstractPoverty remains a persistent structural issue in society, profoundly impacting children’s mental health and resilience. However, the influence of poverty on children’s resilience and its neural underpinnings is not well understood. This study investigates this impact using a nationally representative sample (N = 11878) and neuroimaging techniques to explore the heterogeneity of resilience mechanisms in poor children. Our findings reveal that poor children (living below the federal poverty threshold) experience exacerbated effects of early life adversities (ELAs) on behavioral problems, which persist into adolescence, indicating disrupted resilience. By subtyping poor children based on neural representations of self-regulation (brain activation during stop signal task), we identified two distinct subtypes: subtype-1, with heightened neural activation, exhibited significantly worse resilience; while subtype-2, with reduced activation, showed resilience levels comparable to non-poor children. Two subtypes did not differ significantly in superficial characteristics including ELA exposure and demographics. However, poor children with subtype-1 had thicker left-middle-frontal-gyrus (L-MFG) brain regions, correlating with fewer behavioral problems and weaker ELA impacts, suggesting a unique resilience mechanism. This L-MFG-based resilience mechanism is exclusive to subtype-1, and not observed in subtype-2 or non-poor children. These findings underscore the importance of understanding individual heterogeneity in resilience mechanisms among disadvantaged children. Our study emphasizes the need for future research to delve deeper into adaptation processes to ELAs and poverty, advocating for the exploration of varied resilience mechanisms to mitigate the stigma associated with poverty and guide interventions aimed at narrowing mental health gradient.
Long-term Public Healthcare Burden Associated with Intimate Partner Violence among Canadian Women: A Cohort Study
Authors: Dusing Gabriel John , Essue Beverley M. , O’Campo Patricia , Metheny Nicholas 
Published: June 2024

AbstractIntimate partner violence (IPV) is a major global health issue, yet few studies explore its long-term public healthcare burden in countries with universal healthcare systems. This study analyzes this burden among Canadian women using data from the Neighborhood Effects on Health and Wellbeing survey and Ontario Health Insurance Plan (OHIP) records from 2009-2020. We employed inverse probability weighting with regression adjustment to estimate differences in cumulative costs and OHIP billings between those reporting exposure to IPV during the survey and those who did not. Our sample included 1,094 women, with 38.12% reporting IPV exposure via the Hurt, Insult, Threaten, Scream scale. Findings show a significant public healthcare burden due to IPV: women reporting IPV in 2009 had an average of 17% higher healthcare costs and 41 additional OHIP billings (0.1732;95% CI: 0.0578-0.2886; 41.23;95% CI: 12.63-69.82). Policies prioritizing primary prevention and integration of trauma-informed care among healthcare providers are vital to alleviate the long-term burden on public health systems.
Sex and aging signatures of proteomics in human cerebrospinal fluid identify distinct clusters linked to neurodegeneration
Authors: Seo Dahun , Lee Cheolmin Matthew , Apio Catherine , Heo Gyujin , Timsina Jigyasha , Kohlfeld Pat , Boada Merce , Orellana Adelina , Fernandez Maria Victoria , Ruiz Agustin , Morris John C. , Schindler Suzanne E. , Park Taesung , Cruchaga Carlos , Sung Yun Ju 
Published: June 2024

AbstractSex and age are major risk factors for chronic diseases. Recent studies examining age-related molecular changes in plasma provided insights into age-related disease biology. Cerebrospinal fluid (CSF) proteomics can provide additional insights into brain aging and neurodegeneration. By comprehensively examining 7,006 aptamers targeting 6,139 proteins in CSF obtained from 660 healthy individuals aged from 43 to 91 years old, we subsequently identified significant sex and aging effects on 5,097 aptamers in CSF. Many of these effects on CSF proteins had different magnitude or even opposite direction as those on plasma proteins, indicating distinctive CSF-specific signatures. Network analysis of these CSF proteins revealed not only modules associated with healthy aging but also modules showing sex differences. Through subsequent analyses, several modules were highlighted for their proteins implicated in specific diseases. Module 2 and 6 were enriched for many aging diseases including those in the circulatory systems, immune mechanisms, and neurodegeneration. Together, our findings fill a gap of current aging research and provide mechanistic understanding of proteomic changes in CSF during a healthy lifespan and insights for brain aging and diseases.
Experiences and preferences in Zambia and South Africa for delivery of HIV treatment during a client’s first six months: a cross-sectional survey
Authors: Mutanda Nyasha , Morgan Allison , Kamanga Aniset , Sande Linda , Ntjikelane Vinolia , Maskew Mhairi , Haimbe Prudence , Lumano-Mulenga Priscilla , Rosen Sydney , Scott Nancy 
Published: June 2024

AbstractBackgroundDisengagement from antiretroviral therapy (ART) is highest in the early treatment period (≤6 months after initiation/re-initiation), but low intensity models designed to increase retention generally exclude these clients. We describe client preferences for HIV service delivery in the early treatment period.MethodsFrom 9/2022-6/2023, we surveyed adult clients who were initiating or on ART for ≤6 months at primary health facilities in South Africa and Zambia. We collected data on experiences with and preferences for HIV treatment.ResultsWe enrolled 1,098 participants in South Africa (72% female, median age 33) and 771 in Zambia (67% female, median age 32), 38% and 34% of whom were initiating/re-initiating ART in each country, respectively. While clients expressed varied preferences, most participants (94% in South Africa, 87% in Zambia) were not offered choices regarding service delivery. 82% of participants in South Africa and 36% in Zambia reported receiving a 1-month supply of medication at their most recent visit; however, South African participants preferred 2- or 3-month dispensing (69%), while Zambian participants preferred 3-or 6-month dispensing (85%). Many South African participants (65%) would prefer to collect medication in community settings, while Zambian participants (70%) preferred clinic-based collection. Half of participants desired more one-on-one counselling and health information. Most participants reported positive experiences with providers, but long waiting queues were reported by South African participants.ConclusionsDuring the first six months on ART, many clients would prefer less frequent clinic visits, longer dispensing intervals, and frequent, high-quality counselling. Care models for the early treatment period should reflect these preferences.RegistrationClinicaltrials.govNCT05454839,Clinicaltrials.govNCT05454852
Antipsychotic management in general practice: serial cross-sectional study (2011-2020)
Authors: Woodall Alan , Gampel Alex , Collins Huw , Walker Lauren E , Mair Frances S , Sheard Sally , Symon Pyers , Buchan Iain 
Published: June 2024

AbstractBackgroundLong-term use of antipsychotics confers increased risk of cardiometabolic disease. Ongoing need should be reviewed regularly by psychiatrists.AimTo explore trends in antipsychotic management in general practice, and proportions of patients prescribed antipsychotics receiving psychiatrist review.Design and SettingA serial cross-sectional study using linked general practice and hospital data in Wales (2011-2020).MethodParticipants were adults (≥18 years) registered with general practices in Wales. Outcome measures were prevalence of patients receiving ≥6 antipsychotic prescriptions annually, proportion of patients prescribed antipsychotics receiving annual psychiatrist review, and proportion of patients prescribed antipsychotics registered on UK Serious Mental Illness, Depression and/or Dementia registers, or not on any of these registers.ResultsPrevalence of adults prescribed long-term antipsychotics increased from 1.06% (95%CI 1.04 to 1.07%) in 2011 to 1.45% (95%CI 1.43 to 1.46%) in 2020. The proportion receiving annual psychiatrist review decreased from 59.6% (95%CI 58.9 to 60.4%) in 2011 to 52.0% (95C%CI 51.4 to 52.7%) in 2020. The proportion of antipsychotics prescribed to patients not on the Serious Mental Illness register increased from 50% (95%CI 49 to 51%) in 2011 to 56% (95%CI 56 to 57%) by 2020.ConclusionsPrevalence of long-term antipsychotic use is increasing. More patients are managed by general practitioners without psychiatrist review and are not on monitored disease registers; they thus may be less likely to undergo cardiometabolic monitoring and miss opportunities to optimise or deprescribe antipsychotics. These trends pose risks for patients and need to be addressed urgently.How this fits inAntipsychotics are effective treatments for serious mental illness, but long-term use increases the risk of cardiometabolic disease, therefore ongoing use should be reviewed regularly. There is increasing use of these medications for non-psychotic mental illness by psychiatrists who then discharge patients to sole care by GPs, often for patients who are not captured on disease registers that automate recall for cardiometabolic risk monitoring. This study demonstrates a rising burden of long-term antipsychotic prescribing in general practice, with nearly half of all adult patients not under annual psychiatrist review, and only 44% of long-term antipsychotic prescriptions being issued to patients coded on the Quality and Outcomes Framework (QOF) Serious Mental Illness register. This means many patients taking antipsychotics may be missed for cardiometabolic screening and expert review. Policy changes are required to ensure regular effective review and monitoring to prevent increasing morbidity and early mortality for patients prescribed long-term antipsychotics.
Validation of anthropometric-based weight prediction equations among Ugandan adults: A Cross-sectional study
Authors: Mukasa Zakaria , Ntuulo Juliet Mutanda , Kasirye Ronnie , Olal Emmanuel , Lwanga Christopher , Nankabirwa Victoria , Nuwaha Fred 
Published: June 2024

ABSTRACTIntroductionProper patient management often requires accurate weight estimation. However, the appropriate weight-measuring equipment is not always available in resource-limited settings, making clinicians resort to less reliable methods like the visual estimation of weight often with negative consequences. In this study, we assess the accuracy of anthropometric-based equations in predicting weight in Ugandan adults.MethodsA cross-sectional study was conducted at Kira Health Center IV between December 2021 and February 2022. A sample of 240 adult patients, 18 years and above, was selected by quota sampling, stratified by sex and body mass index. Demographic information was obtained and anthropometric measurements including weight, height, knee height, subscapular skin fold thickness, and circumference measurements were taken. The predicted weight was computed using the proposed equations and the accuracy of the different equations was determined using Bland Altman analysis taking the equation with the best agreement as the most accurate.ResultsOut of 240 participants, 50% were females. The mean (standard deviation) age was 32.5(11.8) years; (34.1(12.9) years for males and 30.8(10.3) years for females). The mean (standard deviation) actual weight was 66.43 (16.33) kg while the mean height was 1.64 (0.09) meters. Using Bland-Altman analysis, Rabito equation (Weight = (0.5759xMAC) + (0.5263xAC) + (1.2452xCC) - (4.8689xS)-32.9241) was found to have the best agreement with the actual weight with a mean difference (standard deviation) of 2.55(6.99) kilograms overall.ConclusionEquation R3 was the most accurate equation for predicting weight among Ugandan adults. Therefore, in the absence of appropriate weighing scales to weigh patients, using this anthropometric-based weight estimation equation can act as a relatively accurate alternative.
Structural Basis for Substrate Binding, Catalysis and Inhibition of Breast Cancer Target Mitochondrial Creatine Kinase by Covalent Inhibitor via Cryo-EM
Authors: Demir Merve , Koepping Laura , Li Ya , Fujimoto Lynn , Bobkov Andrey , Zhao Jianhua , Hitosugi Taro , Sergienko Eduard 
Published: June 2024

AbstractMitochondrial creatine kinases are key players in maintaining energy homeostasis in cells by working in conjunction with cytosolic creatine kinases for energy transport from mitochondria to cytoplasm. High levels of MtCK observed in Her2+ breast cancer and inhibition of breast cancer cell growth by substrate analog, cyclocreatine, indicate dependence of cancer cells on the ‘energy shuttle’ for cell growth and survival. Hence, understanding the key mechanistic features of creatine kinases and their inhibition plays an important role in the development of cancer therapeutics. Herein, we present the mutational and structural investigation on understudied ubiquitous mitochondrial creatine kinase (uMtCK). Our cryo-EM structures and biochemical data on uMtCK showed closure of the loop comprising residue His61 is specific to and relies on creatine binding and the reaction mechanism of phosphoryl transfer depends on electrostatics in the active site. In addition, the previously identified covalent inhibitor CKi showed inhibition in breast cancer BT474 cells, however our biochemical and structural data indicated that CKi is not a potent inhibitor for breast cancer due to strong dependency on the covalent link formation and inability to induce conformational changes upon binding.
TheHydractiniacell atlas reveals cellular and molecular principles of cnidarian coloniality
Authors: Salamanca-Díaz David A. , Horkan Helen R. , García-Castro Helena , Emili Elena , Salinas-Saavedra Miguel , Rossi Maria Eleonora , Álvarez-Presas Marta , Gabhann Rowan Mac , Febrimarsa  , Pérez-Posada Alberto , Kenny Nathan J. , Paps Jordi , Frank Uri , Solana Jordi 
Published: June 2024

AbstractColoniality is a widespread growth form in cnidarians, tunicates, and bryozoans, among others. Despite being modular, composed of multiple zooids and supporting tissues, colonies function as a single physiological unit. A major question in the biology of colonies is the cellular mechanism of generating structurally and functionally distinct colony parts. The cnidarianHydractiniaestablishes colonies with different types of zooids (polyps), interconnected by a gastrovascular system that is attached to the substrate and known as stolons. We obtained single cell transcriptomic profiles of ∼200KHydractiniacells, including isolated stolons and two polyp types. We characterised the majorHydractiniacell types and quantified their abundance across colony parts. Overall, we find that distinct colony parts are characterised primarily by distinct combinations of shared cell types and to a lesser extent by part-specific cell types. Therefore, we propose that both cell type combinations, as well as rarer cell type innovations, have been the main mechanism in the evolution of coloniality in cnidarians. We identified cell type-specific transcription factors (TFs) and gene networks expressed within these cell types. Notably, we discovered a previously unidentified, stolon-specific cell type, which expresses enzymes related to biomineralization and chitin synthesis, reminiscent of molluscan shell matrix proteins that may represent a crucial adaptation to the animal’s habitat. In summary, theHydractiniacell atlas elucidates the fundamental cellular and molecular mechanisms underlying coloniality.
The N-glycosylation defect in Lec5 and Lec9 CHO cells is caused by absence of the DHRSX gene
Authors: Kentache Takfarinas , Althoff Charlotte R. , Caligiore Francesco , Souche Erika , Schulz Céline , Graff Julie , Pieters Eline , Stanley Pamela , Contessa Joseph N. , Schaftingen Emile Van , Matthijs Gert , Foulquier François , Bommer Guido T. , Wilson Matthew P. 
Published: June 2024

AbstractGlycosylation-deficient Chinese hamster ovary (CHO) cell lines have been instrumental in the discovery of N-glycosylation machinery. Yet, the molecular causes of the glycosylation defects in the Lec5 and Lec9 mutants have been elusive, even though for both cell lines a defect in dolichol formation from polyprenol was previously established. We recently found that dolichol synthesis from polyprenol occurs in three steps consisting of the conversion of polyprenol to polyprenal by DHRSX, the reduction of polyprenal to dolichal by SRD5A3 and the reduction of dolichal to dolichol, again by DHRSX.This led us to investigate defective dolichol synthesis in Lec5 and Lec9 cells. Both cell lines showed increased levels of polyprenol and its derivatives, concomitant with decreased levels of dolichol and derivatives, but no change in polyprenal levels, suggesting DHRSX deficiency. Accordingly, N-glycan synthesis and changes in polyisoprenoid levels were corrected by complementation with human DHRSX but not with SRD5A3. Furthermore, the typical polyprenol dehydrogenase and dolichal reductase activities of DHRSX were absent in membrane preparations derived from Lec5 and Lec9 cells, while the reduction of polyprenal to dolichal, catalyzed by SRD5A3, was unaffected. Long-read whole genome sequencing of Lec5 and Lec9 cells did not reveal mutations in the ORF ofSRD5A3, but the genomic region containingDHRSXwas absent. Lastly, we established the sequence of Chinese hamster DHRSX and validated that this protein has similar kinetic properties to the human enzyme. Our work therefore identifies the basis of the dolichol synthesis defect in CHO Lec5 and Lec9 cells.
Targeted and Untargeted Amine Metabolite Quantitation in Single Cells with Isobaric Multiplexing
Authors: Heininen Juho , Movahedi Parisa , Kotiaho Tapio , Kostiainen Risto , Pahikkala Tapio , Teppo Jaakko 
Published: June 2024

AbstractWe developed a single cell amine analysis approach utilizing isobarically multiplexed samples of 6 individual cells along with analyte abundant carrier. This methodology was applied for absolute quantitation of amino acids and untargeted relative quantitation of amines in a total of 108 individual cells using nanoflow LC with high-resolution mass spectrometry. Together with individually determined cell sizes, this provides the first absolute quantification of intracellular metabolites within individual cells. The targeted method was partially validated for 10 amino acids with limits of detection in low attomoles, linear calibration range covering analyte amounts typically from 30 amol to 120 fmol, and correlation coefficients (R) above 0.99. Using the cell sizes determined during dispensing, millimolar intracellular concentrations were determined. The untargeted approach yielded 249 features that were detected in at least 25% of the single cells, providing modest cell type separation on principal component analysis. Using Greedy forward selection with regularized least squares, a sub-selection of 100 features explaining most of the difference, was determined. These features were annotated using MS2 from analyte standards and accurate mass with library search. The approach provides accessible, sensitive, and high-throughput method with the potential to be expanded also to other forms of ultrasensitive analysis.