bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ancestry dependent balancing selection of placental dysferlin at high-altitude
Authors: Gundling William E. , Post Sasha , Illsley Nicholas P. , Echalar Lourdes , Zamudio Stacy , Wildman Derek E. 
Published: March 2023

Introduction: The placenta mediates fetal growth by regulating gas and nutrient exchange between the mother and the fetus. The cell type in the placenta where this nutrient exchange occurs is called the syncytiotrophoblast, which is the barrier between the fetal and maternal blood. Residence at high-altitude is strongly associated with reduced 3rd trimester fetal growth and increased rates of complications such as preeclampsia. We asked whether altitude and/or ancestry-related placental gene expression contributes to differential fetal growth under high-altitude conditions, as native populations have greater fetal growth than migrants to high-altitude.Methods: We have previously shown that methylation differences largely accounted for altitude-associated differences in placental gene expression that favor improved fetal growth among high-altitude natives. We tested for differences in DNA methylation between Andean and European placental samples from Bolivia [La Paz (∼3,600 m) and Santa Cruz, Bolivia (∼400 m)]. One group of genes showing significant altitude-related differences are those involved in cell fusion and membrane repair in the syncytiotrophoblast. Dysferlin (DYSF) shows greater expression levels in high- vs. low-altitude placentas, regardless of ancestry. DYSF has a single nucleotide variant (rs10166384;G/A) located at a methylation site that can potentially stimulate or repress DYSF expression. Following up with individual DNA genotyping in an expanded sample size, we observed three classes of DNA methylation that corresponded to individual genotypes of rs10166384 (A/A &lt; A/G &lt; G/G). We tested whether these genotypes are under Darwinian selection pressure by sequencing a ∼2.5 kb fragment including the DYSF variants from 96 Bolivian samples and compared them to data from the 1000 genomes project.Results: We found that balancing selection (Tajima’s D = 2.37) was acting on this fragment among Andeans regardless of altitude, and in Europeans at high-altitude (Tajima’s D = 1.85).Discussion: This supports that balancing selection acting on dysferlin is capable of altering DNA methylation patterns based on environmental exposure to high-altitude hypoxia. This finding is analogous to balancing selection seen frequency-dependent selection, implying both alleles are advantageous in different ways depending on environmental circumstances. Preservation of the adenine (A) and guanine (G) alleles may therefore aid both Andeans and Europeans in an altitude dependent fashion.
Emergence and circulation of azole-resistant C. albicans, C. auris and C. parapsilosis bloodstream isolates carrying Y132F, K143R or T220L Erg11p substitutions in Colombia
Authors: Ceballos-Garzon Andres , Peñuela Ana , Valderrama-Beltrán Sandra , Vargas-Casanova Yerly , Ariza Beatriz , Parra-Giraldo Claudia M. 
Published: March 2023

MethodsOver a four-year period, 123 Candida bloodstream isolates were collected at a quaternary care hospital. The isolates were identified by MALDI-TOF MS and their fluconazole (FLC) susceptibility patterns were assessed according to CLSI guidelines. Subsequently, sequencing of ERG11, TAC1 or MRR1, and efflux pump activity were performed for resistant isolates.ResultsOut of 123 clinical strains,C. albicans accounted for 37.4%, followed by C. tropicalis 26.8%, C. parapsilosis 19.5%, C. auris 8.1%, C. glabrata 4.1%, C. krusei 2.4% and C. lusitaniae 1.6%. Resistance to FLC reached 18%; in addition, a high proportion of isolates were cross-resistant to voriconazole. Erg11 amino acid substitutions associated with FLC-resistance (Y132F, K143R, or T220L) were found in 11/19 (58%) of FLCresistant isolates. Furthermore, novel mutations were found in all genes evaluated. Regarding efflux pumps, 8/19 (42%) of FLC-resistant Candida spp strains showed significant efflux activity. Finally, 6/19 (31%) of FLC-resistant isolates neither harbored resistance-associated mutations nor showed efflux pump activity. Among FLC-resistant species, C. auris 7/10 (70%) and C. parapsilosis 6/24 (25%) displayed the highest percentages of resistance (C. albicans 6/46, 13%).DiscussionOverall, 68% of FLC-resistant isolates exhibited a mechanism that could explain their phenotype (e.g. mutations, efflux pump activity, or both). We provide evidence that isolates from patients admitted to a Colombian hospital harbor amino acid substitutions related to resistance to one of the most commonly used molecules in the hospital setting, with Y132F being the most frequently detected.
The intervention seasons of thoracic endovascular aortic repair impacted the outcomes for patients with type B aortic dissection
Authors: Zhao Kaiwen , Zhu Hongqiao , He Xiaomin , Liang Taiping , Sun Yudong , Zhou Jian , Jing Zaiping 
Published: March 2023

PurposeThe objective of this research was to investigate whether seasonal variations influence the outcomes of type B aortic dissection (TBAD) patients with thoracic endovascular aortic repair (TEVAR).Patients and methodsFrom 2003 to 2020, a retrospective cohort study was performed, which included 1,123 TBAD patients who received TEVAR. Medical records were used to gather data on baseline characteristics. Outcomes including all-cause mortality and aortic-related adverse events (ARAEs) were tracked and analyzed.ResultsOf the 1,123 TBAD patients in this study, 308 received TEVAR in spring (27.4%), 240 cases in summer (21.4%), 260 cases in autumn (23.2%), and 315 cases in winter (28.0%). Patients in the autumn group had a significantly lower risk of 1-year mortality than those in the spring group (hazard ratio: 2.66, 95% confidence interval: 1.06–6.67, p = 0.037). Kaplan–Meier curves revealed that patients who underwent TEVAR in autumn had a lower risk of 30-day ARAEs (p = 0.049) and 1-year mortality (p = 0.03) than those in spring.ConclusionThis study confirmed that TEVAR operated in autumn for TBAD was associated with a lower risk of 30-day ARAEs and 1-year mortality than in spring.
Building a successful minimally invasive mitral valve repair program before introducing the robotic approach: The Massachusetts General Hospital experience
Authors: van Kampen Antonia , Goudot Guillaume , Butte Sophie , Paneitz Dane C. , Borger Michael A. , Badhwar Vinay , Sundt Thoralf M. , Langer Nathaniel B. , Melnitchouk Serguei 
Published: March 2023

BackgroundPatients with mitral valve prolapse (MVP) requiring surgical repair (MVr) are increasingly operated using minimally invasive strategies. Skill acquisition may be facilitated by a dedicated MVr program. We present here our institutional experience in establishing minimally invasive MVr (starting in 2014), laying the foundation to introduce robotic MVr.MethodsWe reviewed all patients that had undergone MVr for MVP via sternotomy or mini-thoracotomy between January 2013 and December 2020 at our institution. In addition, all cases of robotic MVr between January 2021 and August 2022 were analyzed. Case complexity, repair techniques, and outcomes are presented for the conventional sternotomy, right mini-thoracotomy and robotic approaches. A subgroup analysis comparing only isolated MVr cases via sternotomy vs. right mini-thoracotomy was conducted using propensity score matching.ResultsBetween 2013 and 2020, 799 patients were operated for native MVP at our institution, of which 761 (95.2%) received planned MVr (263 [34.6%] via mini-thoracotomy) and 38 (4.8%) received planned MV replacement. With increasing proportions of minimally invasive procedures (2014: 14.8%, 2020: 46.5%), we observed a continuous growth in overall institutional volume of MVP (n = 69 in 2013; n = 127 in 2020) and markedly improved institutional rates of successful MVr, with 95.4% in 2013 vs. 99.2% in 2020. Over this period, a higher complexity of cases were treated minimally-invasively and increased use of neochord implantation ± limited leaflet resection was observed. Patients operated minimally invasively had longer aortic cross-clamp times (94 vs. 88 min, p = 0.001) but shorter ventilation times (4.4 vs. 4.8 h, p = 0.002) and hospital stays (5 vs. 6 days, p &lt; 0.001) than those operated via sternotomy, with no significant differences in other outcome variables. A total of 16 patients underwent robotically assisted MVr with successful repair in all cases.ConclusionA focused approach towards minimally invasive MVr has transformed the overall MVr strategy (incision; repair techniques) at our institution, leading to a growth in MVr volume and improved repair rates without significant complications. On this foundation, robotic MVr was first introduced at our institution in 2021 with excellent outcomes. This emphasizes the importance of building a competent team to perform these challenging operations, especially during the initial learning curve.
Case Report: Surgery and genetic analysis of a complete androgen insensitivity syndrome family with testicular malignant tumors
Authors: Jiang Lu , Jia Peng , Duan Baofeng , Zhang Yan 
Published: March 2023

Introduction: Complete androgen insensitivity syndrome (CAIS) is a rare sex development disorder that results from X-linked androgen receptor gene mutations. Malignant transformation of the gonads is the most feared complication in postpubertal patients.Methods: In the current report, primary amenorrhea, infertility, and groin mass were symptoms described by a 58-year-old woman and his younger sister. Their two aunts, who shared the same clinical traits, passed away for an unknown reason.Results: After gonadectomy, both patients were diagnosed with seminoma and an extratesticular benign tumor, and the elder sister suffered from breast cancer about a year after the operation. The diagnosis of CAIS was verified by whole-exome sequencing (WES), in which an uncommon mutation (c.2197G&gt;A) in the AR gene was identified.Discussion: This is the first family report of CAIS with germ cell tumors. The identified AR gene mutation based on WES can expand the understanding of CAIS.
A novel SETD2 variant causing global development delay without overgrowth in a Chinese 3-year-old boy
Authors: Wu Yuanyuan , Liu Fang , Wan Ruihua , Jiao Baoquan 
Published: March 2023

Background: Luscan-Lumish syndrome is characterized by macrocephaly, postnatal overgrowth, intellectual disability (ID), developmental delay (DD), which is caused by heterozygous SETD2 (SET domain containing 2) mutations. The incidence of Luscan-Lumish syndrome is unclear. The study was conducted to provide a novel pathogenic SETD2 variant causing atypical Luscan-Lumish syndrome and review all the published SETD2 mutations and corresponding symptoms, comprehensively understanding the phenotypes and genotypes of SETD2 mutations.Methods: Peripheral blood samples of the proband and his parents were collected for next-generation sequencing including whole-exome sequencing (WES), copy number variation (CNV) detection and mitochondrial DNA sequencing. Identified variant was verified by Sanger sequencing. Conservative analysis and structural analysis were performed to investigate the effect of mutation. Public databases such as PubMed, Clinvar and Human Gene Mutation Database (HGMD) were used to collect all cases with SETD2 mutations.Results: A novel pathogenic SETD2 variant (c.5835_c.5836insAGAA, p. A1946Rfs*2) was identified in a Chinese 3-year-old boy, who had speech and motor delay without overgrowth. Conservative analysis and structural analysis showed that the novel pathogenic variant would loss the conserved domains in the C-terminal region and result in loss of function of SETD2 protein. Frameshift mutations and non-sense mutations account for 68.5% of the total 51 SETD2 point mutations, suggesting that Luscan-Lumish syndrome is likely due to loss of function of SETD2. But we failed to find an association between genotype and phenotype of SETD2 mutations.Conclusion: Our findings expand the genotype-phenotype knowledge of SETD2-associated neurological disorder and provide new evidence for further genetic counselling.
Inflammation markers and the risk of hypertension in people living with HIV
Authors: Ou-Yang Hui , Fu Hai-Yan , Luo Yu , Xu Zhao-Yuan , Liu Jun , Gao Rui , Duan Jin-Yu , Mao Ya-Chao , Li Hong-Juan , Du Ying-Rong 
Published: March 2023

BackgroundThe incidence of hypertension is high in people living with HIV (PLWH). High-sensitivity C-reactive protein (hsCRP), systemic inflammation response index (SIRI), and neutrophil-to-monocyte ratio (NMR) are considered economic and convenient parameters that reflect the levels of inflammation in patients. Our aim was to explore whether indirect inflammation markers are associated with hypertension in PLWH.MethodsThis was a case-control study. The case group (hypertension) comprised PLWH with hypertension, and the control group (non-hypertension) comprised sex- and age-(± 3 years)-matched PLWH without hypertension. Demographic parameters, hsCRP, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune- inflammation index (SII), SIRI, lymphocyte-to-monocyte ratio (LMR), platelet-to-neutrophil ratio (PNR), platelet-to-monocyte ratio (PMR), NMR, time to HIV diagnosis, antiretroviral therapy (ART) duration, recent CD4+ and CD8+ cell counts, recent CD4+/CD8+ ratio, recent HIV viral load (HIV-RNA),and recent ART regimen were obtained from the patients’ electronic medical records. A t-test or Wilcoxon rank-sum test was performed to compare differences between the two groups, and conditional logistic regression was used to analyze the risk factors of hypertension. Correlations between inflammation markers and CD4+ cell counts, CD8+ cell counts, and CD4+/CD8+ ratio were analyzed using Spearman’s correlation.ResultsIn the hypertension group, body mass index (BMI), hsCRP, NLR, SII, SIRI, NMR, time to HIV diagnosis, ART duration, CD4+ and CD8+ cell counts, and CD4+/CD8+ ratio, the ratio of HIV-RNA &lt; 100 copies/mL were all higher than those in the non-hypertension group, while the PNR was lower than that in the non-hypertension group. ART duration, CD4+ cell counts, HIV-RNA &lt; 100 copies/mL, hsCRP, SIRI, and NMR were positively associated with hypertensive risk in PLWH. CD8+ cell counts and CD4+/CD8+ ratio was negatively associated with hypertensive risk in PLWH. SIRI was negatively correlated with CD4+ cell counts and CD8+ cell counts, but positively correlated with CD4+/CD8+ ratio.ConclusionsWe identified positive associations between inflammation markers hsCRP, SIRI, NMR and hypertensive risk in PLWH. Alleviating inflammation may help control or delay the occurrence of hypertension in PLWH.
Convalescent human IgG, but not IgM, from COVID-19 survivors confers dose-dependent protection against SARS-CoV-2 replication and disease in hamsters
Authors: King Hannah A. D. , Dussupt Vincent , Mendez-Rivera Letzibeth , Slike Bonnie M. , Tran Ursula , Jackson Nathan D. , Barkei Erica , Zemil Michelle , Tourtellott-Fogt Emily , Kuklis Caitlin H. , Soman Sandrine , Ahmed Aslaa , Porto Maciel , Kitajewski Christopher , Spence Brittany , Benetiene Dalia , Wieczorek Lindsay , Kar Swagata , Gromowski Gregory , Polonis Victoria R. , Krebs Shelly J. , Modjarrad Kayvon , Bolton Diane L. 
Published: March 2023

IntroductionAntibody therapeutic strategies have served an important role during the COVID-19 pandemic, even as their effectiveness has waned with the emergence of escape variants. Here we sought to determine the concentration of convalescent immunoglobulin required to protect against disease from SARS-CoV-2 in a Syrian golden hamster model.MethodsTotal IgG and IgM were isolated from plasma of SARS-CoV-2 convalescent donors. Dose titrations of IgG and IgM were infused into hamsters 1 day prior to challenge with SARS-CoV-2 Wuhan-1.ResultsThe IgM preparation was found to have ~25-fold greater neutralization potency than IgG. IgG infusion protected hamsters from disease in a dose-dependent manner, with detectable serum neutralizing titers correlating with protection. Despite a higher in vitro neutralizing potency, IgM failed to protect against disease when transferred into hamsters.DiscussionThis study adds to the growing body of literature that demonstrates neutralizing IgG antibodies are important for protection from SARS-CoV-2 disease, and confirms that polyclonal IgG in sera can be an effective preventative strategy if the neutralizing titers are sufficiently high. In the context of new variants, against which existing vaccines or monoclonal antibodies have reduced efficacy, sera from individuals who have recovered from infection with the emerging variant may potentially remain an efficacious tool.
Larvae of an invasive scarab increase greenhouse gas emissions from soils and recruit gut mycobiota involved in C and N transformations
Authors: Avila-Arias Helena , Turco Ronald F. , Scharf Michael E. , Groves Russell L. , Richmond Douglas S. 
Published: March 2023

BackgroundSoil-derived prokaryotic gut communities of the Japanese beetle Popillia japonica Newman (JB) larval gut include heterotrophic, ammonia-oxidizing, and methanogenic microbes potentially capable of promoting greenhouse gas (GHG) emissions. However, no research has directly explored GHG emissions or the eukaryotic microbiota associated with the larval gut of this invasive species. In particular, fungi are frequently associated with the insect gut where they produce digestive enzymes and aid in nutrient acquisition. Using a series of laboratory and field experiments, this study aimed to (1) assess the impact of JB larvae on soil GHG emissions; (2) characterize gut mycobiota associated with these larvae; and (3) examine how soil biological and physicochemical characteristics influence variation in both GHG emissions and the composition of larval gut mycobiota.MethodsManipulative laboratory experiments consisted of microcosms containing increasing densities of JB larvae alone or in clean (uninfested) soil. Field experiments included 10 locations across Indiana and Wisconsin where gas samples from soils, as well as JB and their associated soil were collected to analyze soil GHG emissions, and mycobiota (ITS survey), respectively.ResultsIn laboratory trials, emission rates of CO2, CH4, and N2O from infested soil were ≥ 6.3× higher per larva than emissions from JB larvae alone whereas CO2 emission rates from soils previously infested by JB larvae were 1.3× higher than emissions from JB larvae alone. In the field, JB larval density was a significant predictor of CO2 emissions from infested soils, and both CO2 and CH4 emissions were higher in previously infested soils. We found that geographic location had the greatest influence on variation in larval gut mycobiota, although the effects of compartment (i.e., soil, midgut and hindgut) were also significant. There was substantial overlap in the composition and prevalence of the core fungal mycobiota across compartments with prominent fungal taxa being associated with cellulose degradation and prokaryotic methane production/consumption. Soil physicochemical characteristics such as organic matter, cation exchange capacity, sand, and water holding capacity, were also correlated with both soil GHG emission, and fungal a-diversity within the JB larval gut. Conclusions: Results indicate JB larvae promote GHG emissions from the soil directly through metabolic activities, and indirectly by creating soil conditions that favor GHG-associated microbial activity. Fungal communities associated with the JB larval gut are primarily influenced by adaptation to local soils, with many prominent members of that consortium potentially contributing to C and N transformations capable of influencing GHG emissions from infested soil.
On gaps of clinical diagnosis of dementia subtypes: A study of Alzheimer’s disease and Lewy body disease
Authors: Wei Hui , Masurkar Arjun V. , Razavian Narges 
Published: March 2023

IntroductionAlzheimer’s disease (AD) and Lewy body disease (LBD) are the two most common neurodegenerative dementias and can occur in combination (AD+LBD). Due to overlapping biomarkers and symptoms, clinical differentiation of these subtypes could be difficult. However, it is unclear how the magnitude of diagnostic uncertainty varies across dementia spectra and demographic variables. We aimed to compare clinical diagnosis and post-mortem autopsy-confirmed pathological results to assess the clinical subtype diagnosis quality across these factors.MethodsWe studied data of 1,920 participants recorded by the National Alzheimer’s Coordinating Center from 2005 to 2019. Selection criteria included autopsy-based neuropathological assessments for AD and LBD, and the initial visit with Clinical Dementia Rating (CDR) stage of normal, mild cognitive impairment, or mild dementia. Longitudinally, we analyzed the first visit at each subsequent CDR stage. This analysis included positive predictive values, specificity, sensitivity and false negative rates of clinical diagnosis, as well as disparities by sex, race, age, and education. If autopsy-confirmed AD and/or LBD was missed in the clinic, the alternative clinical diagnosis was analyzed.FindingsIn our findings, clinical diagnosis of AD+LBD had poor sensitivities. Over 61% of participants with autopsy-confirmed AD+LBD were diagnosed clinically as AD. Clinical diagnosis of AD had a low sensitivity at the early dementia stage and low specificities at all stages. Among participants diagnosed as AD in the clinic, over 32% had concurrent LBD neuropathology at autopsy. Among participants diagnosed as LBD, 32% to 54% revealed concurrent autopsy-confirmed AD pathology. When three subtypes were missed by clinicians, “No cognitive impairment” and “primary progressive aphasia or behavioral variant frontotemporal dementia” were the leading primary etiologic clinical diagnoses. With increasing dementia stages, the clinical diagnosis accuracy of black participants became significantly worse than other races, and diagnosis quality significantly improved for males but not females.DiscussionThese findings demonstrate that clinical diagnosis of AD, LBD, and AD+LBD are inaccurate and suffer from significant disparities on race and sex. They provide important implications for clinical management, anticipatory guidance, trial enrollment and applicability of potential therapies for AD, and promote research into better biomarker-based assessment of LBD pathology.