bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering the Plasmodium falciparum malaria-specific CD4+ T-cell response: ex vivo detection of high frequencies of PD-1+TIGIT+ EXP1-specific CD4+ T cells using a novel HLA-DR11-restricted MHC class II tetramer
Authors: Schulte Sophia , Heide Janna , Ackermann Christin , Peine Sven , Ramharter Michael , Mackroth Maria Sophia , Woost Robin , Jacobs Thomas , Schulze zur Wiesch Julian 
Published: January 2022

Abstract
Relatively little is known about the ex vivo frequency and phenotype of the Plasmodium falciparum-specific CD4+ T-cell response in humans. The exported protein 1 (EXP1) is expressed by plasmodia at both, the liver stage and blood stage, of infection making it a potential target for CD4+ and CD8+ effector T cells. Here, a fluorochrome-labelled HLA-DRB1∗11:01-restriced MHC class II tetramer derived from the P. falciparum EXP1 (aa62-74) was established for ex vivo tetramer analysis and magnetic bead enrichment in 10 patients with acute malaria. EXP1-specific CD4+ T cells were detectable in 9 out of 10 (90%) malaria patients expressing the HLA-DRB1∗11 molecule with an average ex vivo frequency of 0.11% (0–0.22%) of total CD4+ T cells. The phenotype of EXP1-specific CD4+ T cells was further assessed using co-staining with activation (CD38, HLA-DR, CD26), differentiation (CD45RO, CCR7, KLRG1, CD127), senescence (CD57), and co-inhibitory (PD-1, TIGIT, LAG-3, TIM-3) markers as well as the ectonucleotidases CD39 and CD73. EXP1-specific tetramer+ CD4+ T cells had a distinct phenotype compared to bulk CD4+ T cells and displayed a highly activated effector memory phenotype with elevated levels of co-inhibitory receptors and activation markers: EXP1-specific CD4+ T cells universally expressed the co-inhibitory receptors PD-1 and TIGIT as well as the activation marker CD38 and showed elevated frequencies of CD39. These results demonstrate that MHC class II tetramer enrichment is a sensitive approach to investigate ex vivo antigen-specific CD4+ T cells in malaria patients that will aid further analysis of the role of CD4+ T cells during malaria.
Immunity and pain in the eye: focus on the ocular surface
Authors: Lasagni Vitar Romina Mayra , Bonelli Filippo , Rama Paolo , Ferrari Giulio 
Published: January 2022

SummaryMost ocular diseases are associated with pain. While pain has been generally considered a mere (deleterious) additional symptom, it is now emerging that it is a key modulator of innate/adaptive immunity. Because the cornea receives the highest nerve density of the entire body, it is an ideal site to demonstrate interactions between pain and the immune response. Indeed, most neuropeptides involved in pain generation are also potent regulators of innate and adaptive leukocyte physiology. On the other hand, most inflammatory cells can modulate the generation of ocular pain through release of specific mediators (cytokines, chemokines, growth factors, and lipid mediators). This review will discuss the reciprocal role(s) of ocular surface (and specifically: corneal) pain on the immune response of the eye. Finally, we will discuss the clinical implications of such reciprocal interactions in the context of highly prevalent corneal diseases.
The role of lipid metabolism in shaping the expansion and the function of regulatory T cells
Authors: Pinzon Grimaldos Alessandra , Bini Simone , Pacella Ilenia , Rossi Alessandra , Di Costanzo Alessia , Minicocci Ilenia , D’Erasmo Laura , Arca Marcello , Piconese Silvia 
Published: January 2022

Abstract
Metabolic inflammation, defined as a chronic low-grade inflammation, is implicated in numerous metabolic diseases. In recent years, the role of regulatory T cells (Tregs) as key controllers of metabolic inflammation has emerged, but our comprehension on how different metabolic pathways influence Treg functions needs a deeper understanding. Here we focus on how circulating and intracellular lipid metabolism, in particular cholesterol metabolism, regulates Treg homeostasis, expansion, and functions. Cholesterol is carried through the bloodstream by circulating lipoproteins (chylomicrons, very low-density lipoproteins, low-density lipoproteins). Tregs are equipped with a wide array of metabolic sensors able to perceive and respond to changes in the lipid environment through the activation of different intracellular pathways thus conferring to these cells a crucial metabolic and functional plasticity. Nevertheless, altered cholesterol transport, as observed in genetic dyslipidemias and atherosclerosis, impairs Treg proliferation and function through defective cellular metabolism. The intracellular pathway devoted to the cholesterol synthesis is the mevalonate pathway and several studies have shown that this pathway is essential for Treg stability and suppressive activity. High cholesterol concentrations in the extracellular environment may induce massive accumulation of cholesterol inside the cell thus impairing nutrients sensors and inhibiting the mevalonate pathway. This review summarizes the current knowledge regarding the role of circulating and cellular cholesterol metabolism in the regulation of Treg metabolism and functions. In particular, we will discuss how different pathological conditions affecting cholesterol transport may affect cellular metabolism in Tregs.
Reference range of naïve T and T memory lymphocyte subsets in peripheral blood of healthy adult
Authors: Xia Ying , Liu Aqing , Li Wentao , Liu Yunhe , Zhang Guan , Ye Songshan , Zhao Zhijieruo , Shi Juan , Jia Yingjie , Liu Xu , Guo Yongtie , Chen Huayu , Yu Jianchun 
Published: January 2022

Abstract
Naïve T and T memory cell subsets are closely related to immune response and can provide important information for the diagnosis and treatment of immunological and hematological disorders. Lymphocyte compartment undergoes dramatic changes during adulthood; age-related reference values derived from healthy individuals are crucial. However, extensively detailed reference values of peripheral blood lymphocytes in the whole spectrum of adulthood detected by multi-color flow cytometry on a single platform are rare. Three hundred and nine healthy adult volunteers were recruited from Tianjin in China. The absolute counts and percentages of CD3+CD4+ T cells, CD3+CD8+ T cells, naïve T cells (Tn), T memory stem cells (Tscm), central memory T cells (Tcm), effector memory T cells (Tem), and terminal effector T cells (Tte) were detected by flow cytometry with single platform technologies. Reference range of absolute counts and percentage of T lymphocyte subsets were formulated by different age and gender. The results showed that Tn and Tscm cells, which had stem cell properties, decreased with aging; while, Tcm and Tem increased with aging, which increased from 18 to 64 years old but presented no significant change over the 65 years old. Gender had an influence on the fluctuation of lymphocyte subsets, the absolute count of CD3+CD8+, CD8+Tcm, CD8+Tem in males were higher than those in females. The reference values of percentages and absolute numbers of naïve T and T memory cell subsets can help doctors to understand the immune state of patients and evaluate conditions of prognosis then adjust the treatment for patients. (Chinese Clinic Trial Registry number: ChiCTR-IOR-17014139.)
Trauma moderates the development of the oscillatory dynamics serving working memory in a sex-specific manner
Authors: Killanin Abraham D , Embury Christine M , Picci Giorgia , Heinrichs-Graham Elizabeth , Wang Yu-Ping , Calhoun Vince D , Stephen Julia M , Wilson Tony W 
Published: January 2022

Abstract
Working memory, the ability to hold items in memory stores for further manipulation, is a higher order cognitive process that supports many aspects of daily life. Childhood trauma has been associated with altered cognitive development including particular deficits in verbal working memory (VWM), but the neural underpinnings remain poorly understood. Magnetoencephalography (MEG) studies of VWM have reliably shown decreased alpha activity in left-lateralized language regions during encoding, and increased alpha activity in parieto-occipital cortices during the maintenance phase. In this study, we examined whether childhood trauma affects behavioral performance and the oscillatory dynamics serving VWM using MEG in a cohort of 9- to 15-year-old youth. All participants completed a modified version of the UCLA Trauma History Profile and then performed a VWM task during MEG. Our findings indicated a sex-by-age-by-trauma three-way interaction, whereby younger females experiencing higher levels of trauma had the lowest d’ accuracy scores and the strongest positive correlations with age (i.e. older performed better). Likewise, females with higher levels of childhood trauma exhibited altered age-related alpha changes during the maintenance phase within the right temporal and parietal cortices. These findings suggest that trauma exposure may alter the developmental trajectory of neural oscillations serving VWM processing in a sex-specific way.
Diagnosis and Management of Bacterial Vaginosis: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines
Authors: Muzny Christina A , Balkus Jennifer , Mitchell Caroline , Sobel Jack D , Workowski Kimberly , Marrazzo Jeanne , Schwebke Jane R 
Published: January 2022

Abstract
In preparation for the 2021 Centers for Disease Control and Prevention (CDC) sexually transmitted infections (STIs) treatment guidelines, the CDC convened an advisory group in 2019 to examine recent literature addressing updates in the epidemiology, diagnosis, and management of STIs. This article summarizes recent data in each of these key topic areas as they pertain to bacterial vaginosis (BV), the most common cause of vaginal discharge. The evidence reviewed primarily focused on updates in the global epidemiology of BV, risk factors for BV, data supportive of sexual transmission of BV-associated bacteria, BV molecular diagnostic tests, and novel treatment regimens. Additionally, recent literature on alcohol abstinence in the setting of 5-nitroimidazole use was reviewed.
Fulminant myocarditis following coronavirus disease 2019 vaccination: a case report
Authors: Agdamag Arianne Clare C , Gonzalez Daniel , Carlson Katie , Konety Suma , McDonald William C , Martin Cindy M , Maharaj Valmiki , Alexy Tamas 
Published: January 2022

Abstract

Background
The BNT162b2 vaccine received emergency use authorization from the U.S. Food and Drug Administration for the prevention of severe coronavirus disease 2019 (COVID-19) infection. We report a case of biopsy and magnetic resonance imaging (MRI)-proven severe myocarditis that developed in a previously healthy individual within days of receiving the first dose of the BNT162b2 COVID-19 vaccine.

Case Summary
An 80-year-old female with no significant cardiac history presented with cardiogenic shock and biopsy-proven fulminant myocarditis within 12 days of receiving the BNT162b2 COVID-19 vaccine. She required temporary mechanical circulatory support, inotropic agents, and high-dose steroids for stabilization and management. Ultimately, her cardiac function recovered, and she was discharged in stable condition after 2 weeks of hospitalization. A repeat cardiac MRI 3 months after her initial presentation demonstrated stable biventricular function and continued improvement in myocardial inflammation.

Discussion
Fulminant myocarditis is a rare complication of vaccination. Clinicians should stay vigilant to recognize this rare, but potentially deadly complication. Due to the high morbidity and mortality associated with COVID-19 infection, the clinical benefits of the BNT162b2 vaccine greatly outweighs the risks of complications.
Is data missing? An assessment of publication bias in orthodontic systematic reviews from 2010 to 2021
Authors: Mikelis Filippos , Tzanetakis Giorgos N , Koletsi Despina 
Published: January 2022

Abstract

Aim
To assess the extent of publication bias assessment in systematic reviews (SRs) across the orthodontic literature over the last 12 years and to identify the appropriateness of assessment and association with publication characteristics, including year of publication, journal, searching practices within unpublished literature or attempts to contact primary study authors and others.

Materials and Methods
We searched six journals and the Cochrane Database of Systematic Reviews for relevant articles, since January 2010, until November 2021. We recorded practices interrelated with publication bias assessment, at the SR and meta-analysis level. These pertained to reporting strategies for searching within unpublished literature, attempts to communicate with authors of primary studies and formal assessment of publication bias either graphically or statistically. Potential associations between publication bias assessment practices with variables such as journal, year, methodologist involvement, and others were sought at the meta-analysis level.

Results
A sum of 289 SRs were ultimately included, with 139 of those incorporating at least one available mathematical synthesis. Efforts to search within unpublished literature were reported in 191 out of 289 Reviews (66.1%), while efforts to communicate with primary study authors were recorded for 150 of 289 of those (51.9%). An appropriate strategy plan to address issues of publication bias, conditional on the number of studies available and the methodology plan reported, was followed in 78 of the 139 meta-analyses (56.1%). Formal publication bias assessment was actually reported in 35 of 139 meta-analyses (25.2%), while only half of those (19/35; 54.3%) followed an appropriately established methodology. Ten of the latter 19 studies detected the presence of publication bias (52.6%). Predictor variables of appropriate publication bias assessment did not reveal any significant effects.

Conclusions
Appropriate methodology and rigorous practices for appraisal of publication bias are underreported in SRs within the orthodontic literature since 2010 and up-to-date, while other established methodologies including search strategies for unpublished data or communication with authors appear currently suboptimal.
Investigating the salmon bias effect among international immigrants in Sweden: a register-based open cohort study
Authors: Dunlavy Andrea , Cederström Agneta , Katikireddi Srinivasa Vittal , Rostila Mikael , Juárez Sol P 
Published: January 2022

Abstract

Background
Studies of migration and health have hypothesized that immigrants may emigrate when they develop poor health (salmon bias effect), which may partially explain the mortality advantage observed among immigrants in high-income countries. We evaluated the salmon bias effect by comparing the health of immigrants in Sweden who emigrated with those who remained, while also exploring potential variation by macro-economic conditions, duration of residence and region of origin.

Methods
A longitudinal, open cohort study design was used to assess risk of emigration between 1992 and 2016 among all adult (18+ years) foreign-born persons who immigrated to Sweden between 1965 and 2012 (n = 1 765 459). The Charlson Comorbidity Index was used to measure health status, using information on hospitalizations from the Swedish National Patient Register. Poisson regression models were used to estimate incidence rate ratios (RRs) with 95% confidence intervals (CIs) for emigrating from Sweden.

Results
Immigrants with low (RR = 0.83; 95% CI: 0.76–0.90) moderate (RR = 0.70; 95% CI: 0.62–0.80) and high (RR = 0.62; 95% CI: 0.48–0.82) levels of comorbidities had decreased risk of emigration relative to those with no comorbidities. There was no evidence of variation by health status in emigration during periods of economic recession or by duration of residence. Individuals with low to moderate levels of comorbidities from some regions of origin had an increased risk of emigration relative to those with no comorbidities.

Conclusions
The study results do not support the existence of a salmon bias effect as a universal phenomenon among international immigrants in Sweden.
Population-based screening in children for early diagnosis and treatment of familial hypercholesterolemia: design of the VRONI study
Authors: Sanin Veronika , Schmieder Raphael , Ates Sara , Schlieben Lea Dewi , Wiehler Jens , Sun Ruoyu , Decker Manuela , Sander Michaela , Holdenrieder Stefan , Kohlmayer Florian , Friedmann Anna , Mall Volker , Feiler Therese , Dreßler Arne , Strom Tim M , Prokisch Holger , Meitinger Thomas , von Scheidt Moritz , Koenig Wolfgang , Leipold Georg , Schunkert Heribert ,   the DigiMed Bayern Consortium, Bavarian Pediatricians Consortium
Published: January 2022

Abstract

Background
Heterozygous familial hypercholesterolemia (FH) represents the most frequent monogenic disorder with an estimated prevalence of 1:250 in the general population. Diagnosis during childhood enables early initiation of preventive measures, reducing the risk of severe consecutive atherosclerotic manifestations. Nevertheless, population-based screening programs for FH are scarce.

Methods
In the VRONI study, children aged 5–14 years in Bavaria are invited to participate in an FH screening program during regular pediatric visits. The screening is based on low-density lipoprotein cholesterol measurements from capillary blood. If exceeding 130 mg/dl (3.34 mmol/l), i.e. the expected 95th percentile in this age group, subsequent molecular genetic analysis for FH is performed. Children with FH pathogenic variants enter a registry and are treated by specialized pediatricians. Furthermore, qualified training centers offer FH-focused training courses to affected families. For first-degree relatives, reverse cascade screening is recommended to identify and treat affected family members.

Results
Implementation of VRONI required intensive prearrangements for addressing ethical, educational, data safety, legal and organizational aspects, which will be outlined in this article. Recruitment started in early 2021, within the first months, more than 380 pediatricians screened over 5200 children. Approximately 50 000 children are expected to be enrolled in the VRONI study until 2024.

Conclusions
VRONI aims to test the feasibility of a population-based screening for FH in children in Bavaria, intending to set the stage for a nationwide FH screening infrastructure. Furthermore, we aim to validate genetic variants of unclear significance, detect novel causative mutations and contribute to polygenic risk indices (DRKS00022140; August 2020).
Detection and quantification of Bacillus cereus and its spores in raw milk by qPCR, and distinguish Bacillus cereus from other bacteria of the genus Bacillus
Authors: Liang Lijiao , Wang Ping , Qu Tianming , Zhao Xiaomei , Ge Yiqiang , Chen Ying 
Published: January 2022

Abstract

Introduction
Raw milk is the basic raw material of dairy products. Bacillus cereus (B. cereus) is a typical conditional pathogenic bacteria and cold-phagocytic spoilage bacteria in raw milk.

Materials and Methods
In this study, a quantitative polymerase chain reaction (qPCR) method for detecting B. cereus in raw milk was established. The specificity of the method was verified by using other Bacillus bacteria and pathogenic bacteria; the sensitivity of the method was evaluated by preparing recombinant plasmids and simulated contaminated samples; and the applicability of the method was verified using pure spore DNA. The actual sample detection was completed by using the established qPCR method.

Results
The qPCR established in this study can specifically detect B. cereus in raw milk. The limit of detection of the method was as low as 200 CFU/mL, the limit of quantification ranged from 2×102 to 2×108 CFU/mL, and the amplification efficiency of qPCR was 96.6%.

Conclusions
The method established in this study can distinguish B. cereus from other Bacillus bacteria, and spore DNA can be used as the detection object. This method has the advantages of strong specificity, high sensitivity, wide application range, and short detection time, which is expected to be applied in the dairy industry.
Bidirectional Introgression between Mus musculus domesticus and Mus spretus
Authors: Banker Sarah E , Bonhomme François , Nachman Michael W 
Published: January 2022

Abstract
Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles—including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
Influence of Long-term Nonaspirin NSAID Use on Risk of Frailty in Men ≥60 Years: The Physicians’ Health Study
Authors: Orkaby Ariela R , Ward Rachel , Chen Jiaying , Shanbhag Akshay , Sesso Howard D , Gaziano J Michael , Djousse Luc , Driver Jane A 
Published: January 2022

Abstract

Background
Inflammation is a central pathway leading to frailty but whether commonly used nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can prevent frailty is unknown.

Methods
Prospective cohort study of male physicians ≥60 who participated in the Physicians’ Health Study. Annual questionnaires collected data on NSAID use, lifestyle, and morbidity. Average annual NSAID use was categorized as 0 days/year, 1–12 days/year, 13–60 days/year, and &gt;60 days/year. Frailty was assessed using a validated 33-item frailty index. Propensity score inverse probability of treatment weighting was used to address confounding by indication and logistic regression models estimated odds ratios (ORs) of prevalent frailty according to nonaspirin NSAID use.

Results
A total of 12 101 male physicians were included (mean age 70 ± 7 years, mean follow-up 11 years). Reported NSAID use was 0 days/year for 2 234, 1–12 days/year for 5 812, 13–60 days/year for 2 833, and &gt;60 days/year for 1 222 participants. A total of 2 413 participants (20%) were frail. Higher self-reported NSAID use was associated with greater alcohol use, smoking, arthritis, hypertension, and heart disease, while less NSAID use was associated with coumadin use and prior bleeding. After propensity score adjustment, all characteristics were balanced. ORs (95% confidence intervals) of prevalent frailty were 0.90 (0.80–1.02), 1.02 (0.89–1.17), and 1.26 (1.07–1.49) for average NSAID use of 1–12 days/year, 13–60 days/year, and &gt;60 days/year, compared to 0 days/year (p-trend &lt; .001).

Conclusions
Long-term use of NSAIDs at high frequency is associated with increased risk of frailty among older men. Additional study is needed to understand the role of anti-inflammatory medication in older adults and its implication for overall health.