bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to Detect Antibodies Against Babesia divergens in Human Blood Samples
Authors: Tijani Muyideen Kolapo , Svensson Joel , Adlerborn Paula , Danielsson Lena , Teleka Alexandra , Lövmar Matilda Ljungqvist , Lindgren Per-Eric , Forsberg Pia , Persson Kristina E M 
Published: January 2024

Abstract

Background
Today only indirect fluorescent antibody assays (IFAs) are commercially available to detect antibodies against Babesia divergens in humans. IFA is subjective and requires highly experienced staff. We have therefore developed an enzyme-linked immunosorbent assay (ELISA)–based method for measuring anti–B. divergens immunoglobulin G antibodies in human blood samples.

Methods
Crude merozoite extract from in vitro cultures of a new B. divergens isolate was used in ELISA to detect antibodies in different sets of samples: Borrelia burgdorferi–positive samples, healthy individuals, tick-bitten individuals including follow-up samples 3 months later, positive control samples from patients with an active Babesia infection, and samples from malaria-endemic regions. As a reference, IFA was used to detect antibodies in the tick-bitten samples. Western blot was used to evaluate reactions against specific bands in extracts with/without parasites.

Results
Using IFA as the reference method, the sensitivity and specificity of the ELISA were 86% (12/14) and 100% (52/52). There was a very high correlation (r = −0.84; P = .0004) between IFA dilution factors and ELISA absorbances among the samples classified as positive. Five percent of the B. burgdorferi–positive samples were judged as weakly positive and 5% as strongly positive in our ELISA. Western blot showed that the immunodominant antigens (∼120 kDa) were from merozoites and not from erythrocytes.

Conclusions
This ELISA can detect antibodies directed against B. divergens, and it can be a useful and easy assay to handle compared with IFA. The ELISA can also measure high and low levels of antibodies, which could give insight into the recency of a B. divergens infection.
Overexpression of lysophospholipid acyltransferase, LPLAT10/LPCAT4/LPEAT2, in the mouse liver increases glucose‐stimulated insulin secretion
Authors: Shimizu Kahori , Ono Moe , Mikamoto Takenari , Urayama Yuya , Yoshida Sena , Hase Tomomi , Michinaga Shotaro , Nakanishi Hiroki , Iwasaki Miho , Terada Tomoyuki , Sakurai Fuminori , Mizuguchi Hiroyuki , Shindou Hideo , Tomita Koji , Nishinaka Toru 
Published: January 2024

AbstractPostprandial hyperglycemia is an early indicator of impaired glucose tolerance that leads to type 2 diabetes mellitus (T2DM). Alterations in the fatty acid composition of phospholipids have been implicated in diseases such as T2DM and nonalcoholic fatty liver disease. Lysophospholipid acyltransferase 10 (LPLAT10, also called LPCAT4 and LPEAT2) plays a role in remodeling fatty acyl chains of phospholipids; however, its relationship with metabolic diseases has not been fully elucidated. LPLAT10 expression is low in the liver, the main organ that regulates metabolism, under normal conditions. Here, we investigated whether overexpression of LPLAT10 in the liver leads to improved glucose metabolism. For overexpression, we generated an LPLAT10‐expressing adenovirus (Ad) vector (Ad‐LPLAT10) using an improved Ad vector. Postprandial hyperglycemia was suppressed by the induction of glucose‐stimulated insulin secretion in Ad‐LPLAT10‐treated mice compared with that in control Ad vector‐treated mice. Hepatic and serum levels of phosphatidylcholine 40:7, containing C18:1 and C22:6, were increased in Ad‐LPLAT10‐treated mice. Serum from Ad‐LPLAT10‐treated mice showed increased glucose‐stimulated insulin secretion in mouse insulinoma MIN6 cells. These results indicate that changes in hepatic phosphatidylcholine species due to liver‐specific LPLAT10 overexpression affect the pancreas and increase glucose‐stimulated insulin secretion. Our findings highlight LPLAT10 as a potential novel therapeutic target for T2DM.
Military Veteran Matriculation in US Physician Associate/Assistant Programs
Authors: Broughton Adam , Landry Alexis , Showstark Mary , Barry Carey L. , Najmabadi Shahpar , Rolls Joanne , Honda Trenton 
Published: January 2024

Introduction
This study aims to determine whether veterans have differential access to physician associate/assistant (PA) education by examining likelihood of matriculation relative to nonveteran peers. We explore associations between veteran status and likelihood of matriculation for change over time and whether effects differ among active duty versus non–active-duty applicants.

Methods
Multivariate logistic regression was used to investigate associations between self-identified military status and likelihood of PA program matriculation in five Centralized Applicant Services for Physician Assistants admissions cycles (2012–2013, 2014–2015, 2016–2017, 2018–2019, 2020–2021). Models controlled for age, sex, race/ethnicity, patient care experience hours, total undergraduate grade point average, and number of applications submitted and applied a Bonferroni correction for alpha inflation.

Results
Veteran applicant numbers were small across the study time frame but increased from 2012 (n = 708) to 2020 (n = 978), representing a 38% increase over the lookback period. Despite growth, the proportion of veterans in the matriculant pool has decreased from 4.2% in 2012 to 3.0% in 2020. In unadjusted models, military status was not strongly associated with odds of matriculation. In adjusted models, both veteran and active-duty status were associated with higher odds of matriculation, although this increase was not statistically significant at the 0.005 level for applicants on active-duty.

Discussion
Military veterans and active-duty military personnel have higher likelihood of matriculation into US PA programs relative to nonveteran peers. The proportion of veterans in the matriculant pool has decreased over time. This suggests that while PA programs seems to value previous military experience, further efforts to evaluate and address barriers to military veterans in applying for admissions is needed.
Effects of Ziprasidone or Haloperidol on Theory of Mind in Patients With Schizophrenia: A 16-week Pilot Trial
Authors: Zhong Jie , Jia Yuan , Zhu Hong , Wang Dan , Jia Hongxiao 
Published: January 2024

Objectives:
Schizophrenia is associated with impairment in theory of mind (ToM), which is defined as the ability to make judgments about mental states and is related to medial prefrontal cortical activity. Ziprasidone, but not haloperidol, is known to have a protective effect in the medial prefrontal cortex. Thus, we hypothesized that these 2 drugs would have different efficacy in improving ToM task performance in patients with schizophrenia.

Methods:
Patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of schizophrenia matched for sex, duration of illness, and education were randomized to receive ziprasidone (n=30) or haloperidol (n=30). All patients were assessed using the Positive and Negative Syndrome Scale and the Personal and Social Functioning Scale. ToM was assessed using a first-order false belief task, a second-order false belief task, the faux-pas task, and the Reading the Mind in the Eyes Task, in order of developmental complexity and difficulty. The primary outcome was change in ToM performance from baseline to 16 weeks of treatment.

Results:
For the first-order false belief task, there were no significant differences between the groups (P>0.05). For the second-order false belief task, the interaction effect was significant (P<0.05), and the simple effect of time showed a significant difference only in the ziprasidone group (P<0.001). For the faux-pas task, the interaction effect was not significant (P>0.05). For the Reading the Mind in the Eyes Task, the interaction effect was significant (P<0.05), and the simple effect of time showed a significant difference only in the ziprasidone group (P<0.001). The Positive and Negative Syndrome Scale results were similar between the groups. The ziprasidone group performed better than the haloperidol group on the Personal and Social Functioning Scale. There were no major safety concerns or adverse events.

Conclusions:
The findings of this study suggest that ziprasidone could improve ToM and might be superior to haloperidol for improving complex ToM as well as personal and social functioning in patients with schizophrenia.

Trial Registration Chinese Clinical Trial Register:
ChiCTR2200060542.
Patient and Caregiver Depression in Jordan After a First Stroke
Authors: Aldabbour Belal , Al Qawasmeh Majdi , Elamassie Samah , Abuabada Amal , Abdelrahman Khalid , Zahran Mohammad , Khweileh Mays , El-Salem Khalid 
Published: January 2024

Background:
Poststroke depression among patients is well-recognized, while caregiver depression is understudied. The interaction between patient and caregiver depression is also unclear.

Methods:
This cross-sectional and follow-up study recruited 108 patient-caregiver dyads after the first-ever stroke. Demographic and clinical data, stroke severity (NIH Stroke Scale score), functional outcome (Barthel Index), and residual disability (modified Rankin Score) were documented. Using the self-reported Patient Health Questionnaire-9, we screened patients and caregivers for depressive symptoms upon admission and after 1 month. Changes in the prevalence and severity of depression were calculated. The Pearson correlation test and logistic regression analysis were conducted to evaluate both the correlation between both groups and significant predictors of depression.

Results:
In total, 89 patients and 96 caregivers responded to both screenings. Depression was reported by 13.5% and 27.0% of patients on admission and after 1 month, and 9.4% and 18.8% of caregivers, respectively. Caregiver depression on admission was significantly correlated with patient depression on admission (P=0.031). In addition, depression in caregivers after 1 month was a significant predictor of patient depression (P=0.008). Predictors of caregiver depression after 1 month were female caregivers (P=0.026), caring for a male patient (P=0.045), higher mRS scores after 1 month (P=0.013), longer admissions (P=0.017), caregiver between 17 and 35 years of age compared with 54 to 70 years of age (P=0.030), and caring for a patient with poststroke depression at 1 month poststroke (P=0.003).

Conclusions:
Both stroke survivors and their caregivers are at high risk for depression, with a potential interaction between depression in the 2 groups.
Pupil size and eye movements differently index effort in both younger and older adults
Authors: Herrmann Björn , Ryan Jennifer D. 
Published: January 2024

AbstractThe assessment of mental effort is increasingly relevant in neuro-cognitive and lifespan domains. Pupillometry, the measure of the pupil size, is often used to assess effort but has disadvantages. Analysis of eye movements may provide an alternative, but research has been limited to easy and difficult task demands in younger adults. An effort measure must be sensitive to the whole effort profile, including ‘giving up’ effort investment, and capture effort in different age groups. The current study comprised three experiments in which younger (N=66) and older adults (N=44) listened to speech masked by background babble at different signal-to-noise ratios associated with easy, difficult, and impossible speech comprehension. We expected individuals to invest little effort for easy and impossible speech (‘giving up’) but to exert effort for difficult speech. Indeed, pupil size was largest for difficult, but lower for easy and impossible speech. In contrast, gaze dispersion decreased with increasing speech masking in both age groups. Critically, gaze dispersion during difficult speech returned to levels similar to easy speech after sentence offset, when acoustic stimulation was similar across conditions, whereas gaze dispersion during impossible speech continued to be reduced. These findings show that a reduction in eye movements is not a byproduct of acoustic factors, but instead suggest that neuro-cognitive processes, different from arousal-related systems regulating the pupil size, drive reduced eye movements during high task demands. The current data thus show that effort in one sensory domain (audition) differentially impacts distinct functional properties in another sensory domain (vision).Significance statementThe assessment of mental effort is increasingly relevant in many domains. Here, we investigated the sensitivity of a novel measure of effort - the spatial dispersion of eye movements - and compared it to pupillometry, which is a more common effort-assessment tool. Individuals listened to speech masked by background babble at levels associated with easy, difficult, and impossible speech comprehension. Pupil size was largest for difficult, but lower for easy and impossible speech conditions (giving up listening). In contrast, the spatial dispersion of eye movements decreased with increasing speech masking, but this effect was independent of acoustic factors. Instead, the current results suggest that neuro-cognitive processes, different from arousal-related systems regulating the pupil size, drive reduced eye movements during high task demands.
Excess Mortality in the United States, 2020-21: County-level Estimates for Population Groups and Associations with Social Vulnerability
Authors: Kandula Sasikiran , Keyes Katherine M. , Yaari Rami , Shaman Jeffrey 
Published: January 2024

AbstractTo assess the excess mortality burden of Covid-19 in the United States, we estimated sex, age and race stratified all-cause excess deaths in each county of the US during 2020 and 2021. Using spatial Bayesian models trained on all recorded deaths between 2003-2019, we estimated 463,187 (95% uncertainty interval (UI): 426,139 – 497,526) excess deaths during 2020, and 544,105 (95% UI: 492,202 – 592,959) excess deaths during 2021 nationally, with considerable geographical heterogeneity.Excess mortality rate (EMR) nearly doubled for each 10-year increase in age and was consistently higher among men than women. EMR in the Black population was 1.5 times that of the White population nationally and as high as 3.8 times in some states. Among the 25-54 year population excess mortality was highest in the American Indian/Alaskan Native (AI/AN) population among the four racial groups studied, and in a few states was as high as 6 times that of the White population.Strong association of EMR with county-level social vulnerability was estimated, including positive associations with prevalence of disability (standardized effect: 40.6 excess deaths per 100,000), older population (37.6), poverty (23.6), and unemployment (18.5), whereas population density (−50), higher education (−38.6), and income (−35.4) were protective.Together, these estimates provide a more reliable and comprehensive understanding of the mortality burden of the pandemic in the US thus far. They suggest that Covid-19 amplified social and racial disparities. Short-term measures to protect more vulnerable groups in future Covid-19 waves and systemic corrective steps to address long-term societal inequities are necessary.Significance StatementAll-cause excess mortality estimates, the difference between observed all-cause deaths and deaths expected in the absence of a pandemic, can help more fully assess the pandemic’s burden than direct Covid-19 mortality. Our estimates, based on a 17-year record of all deaths in the US and a Bayesian spatial model, quantify the differences in excess mortality across counties and by population age, race and sex, as well as between the first and second years of the pandemic. Furthermore, our results indicate that population-level socioeconomic indicators such as poverty, unemployment and educational attainment had considerable effect on excess mortality during the pandemic. Sustained efforts to protect vulnerable populations during future waves of Covid-19 (and other public health emergencies) remain vital.
Feasibility, usability, acceptability and Efficacy of a novel leg strengthening device (S-Press) for strengthening leg muscles and improving physical impairment during hospital admission
Authors: Maden-Wilkinson TM. , Griffiths C. , Lakkappa B. , Walker K. , Kennerley CL , Turner JJ. 
Published: January 2024

AbstractBackgroundDeconditioning due to in-patients’ stays is predictive of delayed discharges and readmissions; preserving muscle mass and strength in order for patients to remain independent should be of utmost priority. Progressive resistance training offers the most cost-effective way of doing this; however, it is not routinely done.ObjectiveTo examine the feasibility, usability and acceptability of a novel in-bed strength training device (S-Press) by patients and staff members within an in-patient rehabilitation ward in the NHS.MethodsUsing a mixed methods approach, 6 patients who performed resistance training on the S-Press device and, alongside 3 healthcare professionals, were interviewed. Data were thematically analysed to examine individuals’ perspectives and perceptions on the feasibility, useability and acceptability of the S-Press. In addition, measures of sit to stand and muscle ultrasound were conducted before use and before discharge. For indications of safety, heart rate and blood pressure measures were taken during each session.ResultsPatients found the S-Press easy and comfortable to use and enjoyed using it as an adjunct therapy during in-patient stay. Healthcare professionals using the S-Press noted that it improved mobility allowing patients to gradually build up muscle strength in a safe and motivating way. All participants improved sit to stand performance with use of the S-Press. There were no significant differences observed in heart rate or blood pressure during each session, indicating the safety of S-Press use.ConclusionFrom this proof-of-concept study, use of the S-Press to improve muscle strength and physiological function in in-patients is feasible and an acceptable intervention. Further work should focus on use with wider patient demographics and conditions.
Distinct chikungunya virus polymerase palm subdomains contribute to virus replication and virion assembly
Authors: Martin Marie-France , Bonaventure Boris , McCray Nia E. , Peersen Olve B. , Rozen-Gagnon Kathryn , Stapleford Kenneth A. 
Published: January 2024

AbstractAlphaviruses encode an error-prone RNA-dependent RNA polymerase (RdRp), nsP4, required for genome synthesis, yet how the RdRp functions in the complete alphavirus life cycle is not well-defined. Previous work using chikungunya virus (CHIKV) has established the importance of the nsP4 residue cysteine 483 in maintaining viral genetic fidelity. Given the location of residue C483 in the nsP4 palm domain, we hypothesized that other residues within this domain and surrounding subdomains would also contribute to polymerase function. To test this hypothesis, we designed a panel of nsP4 variants via homology modeling based on the Coxsackievirus B3 3 polymerase. We rescued each variant in both mammalian and mosquito cells and discovered that the palm domain and ring finger subdomain contribute to polymerase host-specific replication and genetic stability. Surprisingly, in mosquito cells, these variants in the ring finger and palm domain were replication competent and produced viral structural proteins, but they were unable to produce infectious progeny, indicating a yet uncharacterized role for the polymerase in viral assembly. Finally, we have identified additional residues in the nsP4 palm domain that influence the genetic diversity of the viral progeny, potentially via an alteration in NTP binding and/or discrimination by the polymerase. Taken together, these studies highlight that distinct nsP4 subdomains regulate multiple processes of the alphavirus life cycle, placing nsP4 in a central role during the switch from RNA synthesis to packaging and assembly.Author SummaryChikungunya virus (CHIKV) is a re-emerging alphavirus transmitted to humans by mosquitoes and causing frequent explosive outbreaks. Its replication relies on a polymerase that incorporates a significant number of errors in the new genomes, making it a good candidate to develop vaccines or antiviral strategies. However, little is known on alphavirus polymerase function in alternate hosts. To begin to understand how the CHIKV polymerase nsP4 functions, we designed a panel of nsP4 variants taking advantage of the conservation of polymerase structure across positive strand RNA viruses. We discovered that the palm domain and ring finger of the polymerase were involved in host-specific RNA replication, genetic stability, and virus assembly. In addition, we demonstrated that the palm domain directly impacted the generation of viral genetic diversity. Taken together, these findings add further evidence to the crucial impact of the core palm domain of CHIKV polymerase not only on the replication of the RNA itself, but also on the genetic stability of the protein, as well as its involvement in viral assembly.
Pre-Columbian treponemes clarify worldwide spread of treponematosis
Authors: Mattéo Gueyrard , Pierre Pontarotti , Michel Drancourt , Laurent Abi-Rached 
Published: January 2024

AbstractSyphilis dramatically hit Europe at the end of the fifteen century before spreading to other continents. Yet the origin of the sudden pandemic in the Old World remains debated, in particular because the leading Columbus hypothesis of a New World origin of historical syphilis in Europe lacks paleomicrobiological confirmation. Here we screened a worldwide set of >1,700 ancient humans and identified ancientTreponema pallidumstrains in two pre-Columbian child sacrifices from Tlatelolco, Mexico. Over 12,000Treponema-specific reads were recovered to define a novelTreponema pallidumancient population:Treponema pallidumstr.tlatelolcoensis. Phylogenetics show that this population displays ancestral features but also bears the genetic building blocks of disease-causing modernTreponema pallidumsubspecies, hence demonstrating how pre-Colombian Americas were the source of worldwide spread of treponematosis.
High-throughput analysis of membrane fluidity unveils a hidden dimension in immune cell states
Authors: Andronico Luca A. , Jiang Yidan , Carannante Valentina , Iskrak Sofia , Sandoz Patrick A. , Mikes Jaromir , Klymchenko Andrey , Buggert Marcus , Österborg Anders , Önfelt Björn , Brodin Petter , Sezgin Erdinc 
Published: January 2024

AbstractCell membranes undergo biophysical remodelling as an adaptation to the surroundings and to perform specific biological functions. However, the extent and relevance of such changes in human immune systems remain unknown, largely due to the lack of high throughput and multidimensional methodologies. Here, we describe a cytometry-based method with single-cell resolution which fills this technological gap by combining biophysical profiling with conventional biomarker analysis. This platform allows to reveal notable cell type-dependent remodelling of membrane fluidity during immune stimulations and in diseases. Using immune cells exposed to tumour microenvironment as well as from long COVID and chronic lymphocyte leukaemia patients, we demonstrate that membrane fluidity is orthogonal to surface marker expression. Moreover, this biophysical parameter identifies new functional and pathological states of immune cells previously undetectedviasurface marker profiling alone. Our findings will contribute to a more precise definition of immune cell states based on their biophysical properties and will pave the way for a better understanding of the functional heterogeneity of immune cells.