bluuebunny/crossref_metadata_2025_split huggingface dataset:
The gut microbiome and antibiotic resistome of chronic diarrhea rhesus macaques (Macaca mulatta) and its similarity to the human gut microbiome
Authors: Yang Shengzhi , Liu Yu , Yang Nan , Lan Yue , Lan Weiqi , Feng Jinyi , Yue Bisong , He Miao , Zhang Liang , Zhang Anyun , Price Megan , Li Jing , Fan Zhenxin 
Published: February 2022

Abstract
Background
Chronic diarrhea is a common disease causing morbidity and mortality of captive rhesus macaques (RMs, Macaca mulatta). Chronic diarrhea in RMs is typically characterized by long-term diarrhea and a weak response to antibiotic treatment. Diarrhea is also a common disease in humans and can cause death. However, the etiology of about half of diarrheal cases of humans is still unclear. Therefore, we performed shotgun metagenomic sequencing to characterize the differences in the gut microbiome and resistome of chronic diarrhea RMs and asymptomatic individuals.

Results
Our results showed Lactobacillus spp. (mainly L. johnsonii, L. reuteri and L. amylovorus) were significantly depleted in chronic diarrhea RM guts compared to asymptomatic individuals (5.2 vs 42.4%). Functional annotation of genes suggested these Lactobacillus spp. carried genes involved in the adhesion of intestinal epithelial cells and production of bacteriocin. Chronic diarrhea RM guts also had a significantly greater abundance of many other gut bacteria, including mucin-degrading bacteria and opportunistic pathogens. The metabolic pathways of chronic diarrhea RM gut microbiome were enriched in aerobactin biosynthesis, while the metabolic pathways of asymptomatic RM gut microbiome were enriched in the production of short-chain fatty acids (SCFAs). Chronic diarrhea RM guts had a significantly greater abundance of antibiotic resistance genes (ARGs), such as ermF, aph(3’)-IIIa, ermB, and floR. The strains isolated from feces and tissue fluid of chronic diarrhea RMs had higher resistance rates to the majority of tested antibiotics, but not cephamycin and carbapenem antibiotics. Gut microbial composition comparisons showed that several captive nonhuman primate (NHP) guts were more similar to the guts of humans with a non-westernized diet than humans with a westernized diet. Chronic diarrhea RM gut microbiome was strikingly similar to rural-living humans with diarrhea and humans with a non-westernized diet than asymptomatic RMs.

Conclusions
Our results suggested chronic diarrhea significantly altered the composition and metabolic pathways of the RM gut microbiome. The frequent use of antibiotics caused antibiotic resistance in chronic diarrhea RM gut microbiome with serious consequences for individual treatment and survival. The findings of this study will help us to improve the effective prevention and treatment of diarrhea in RMs.
Microeukaryotic gut parasites in wastewater treatment plants: diversity, activity, and removal
Authors: Freudenthal Jule , Ju Feng , Bürgmann Helmut , Dumack Kenneth 
Published: February 2022

AbstractBackgroundDuring wastewater treatment, the wastewater microbiome facilitates the degradation of organic matter, reduction of nutrients, and removal of gut parasites. While the latter function is essential to minimize public health risks, the range of parasites involved and how they are removed is still poorly understood.ResultsUsing shotgun metagenomic (DNA) and metatranscriptomic (RNA) sequencing data from ten wastewater treatment plants in Switzerland, we were able to assess the entire wastewater microbiome, including the often neglected microeukaryotes (protists). In the latter group, we found a surprising richness and relative abundance of active parasites, particularly in the inflow. Using network analysis, we tracked these taxa across the various treatment compartments and linked their removal to trophic interactions.ConclusionsOur results indicate that the combination of DNA and RNA data is essential for assessing the full spectrum of taxa present in wastewater. In particular, we shed light on an important but poorly understood function of wastewater treatment – parasite removal.
Feasibility and preliminary efficacy of the LEAD trial: a cluster randomized controlled lifestyle intervention to improve hippocampal volume in older adults at-risk for dementia
Authors: Koblinsky N. D. , Anderson N. D. , Ajwani F. , Parrott M. D. , Dawson D. , Marzolini S. , Oh P. , MacIntosh B. , Middleton L. , Ferland G. , Greenwood C. E. 
Published: February 2022

Abstract
Background
Healthy diet and exercise are associated with reduced risk of dementia in older adults. The impact of diet and exercise interventions on brain health is less consistent, especially with dietary interventions which rely on varying approaches. Our objective was to evaluate the feasibility and preliminary efficacy of a 6-month intervention combining exercise with a novel dietary counseling approach to improve hippocampal volume among older adults at-risk for dementia.

Methods
Participants with vascular risk factors and subjective cognitive decline or early mild cognitive impairment were cluster randomized in groups of 3–4 to the diet intervention (DIET) or control education (ED) group. All participants engaged in 1 h of supervised exercise per week and additional exercise at home. DIET involved 1 h per week of group-based dietary counseling comprising education, goal setting, and strategy training. ED involved 1 h per week of group-based brain health education classes. Our primary outcome was change in hippocampal volume from baseline to 6 months. Secondary outcomes included changes in cognitive function, blood biomarkers, diet, and fitness. Recruitment challenges and early discontinuation of the trial due to COVID-19 necessitated a revised focus on feasibility and preliminary efficacy.

Results
Of 190 older adults contacted, 14 (7%) were eligible and enrolled, constituting 21% of our recruitment target. All participants completed the intervention and attended 90% of exercise and DIET/ED sessions on average. All 6-month assessments prior to COVID-19 were completed but disruptions to in-person testing resulted in incomplete data collection. No serious adverse events occurred and all participants expressed positive feedback about the study. Preliminary findings did not identify any significant changes in hippocampal volume; however, substantial improvements in diet and HbA1c were observed with DIET compared to ED (d = 1.75 and 1.07, respectively).

Conclusions
High adherence and retention rates were observed among participants and preliminary findings illustrate improvements in diet quality and HbA1c. These results indicate that a larger trial is feasible if difficulties surrounding recruitment can be mitigated.

Trial registration
ClinicalTrials.gov identifier: NCT03056508.
COVID-19 screening before gastrointestinal procedures
Authors: Eliwa Ahmed , Osman Osman Mohamed , Helal Ahmed , Mohamed Abdelgawad Saied , ElFayoumie Mohammed , Eldamarawy Ramadan , Mostafa Sadek , Elsharkawy Ashraf , Makboul Khaled S. , Elshennawy Salwa I. , Abdelhady Mahmoud , Elbahrawy Ashraf 
Published: February 2022

Abstract
Background
In March 2020, the World Health Organization declared coronavirus 2019 (COVID-19) a global pandemic. We aimed to assess the ability of COVID-19 screening to detect preprocedural infection at the gastrointestinal units. One hundred and three patients indicated for gastrointestinal tract interventional procedures were included. All patients surveyed for COVID-19-related symptoms and COVID-19 rapid IgM/IgG antibodies. Symptomatic and COVID-19 antibody-positive patients further tested for COVID-19 reverse transcriptase by polymerase chain reaction (RT-PCR). All patients contacted, 14 days after the procedure and asked about the possible development of COVID-19. All health care workers (HCWs) (n=18) were screened weekly for COVID-19-related symptoms.

Results
The mean age was 46.11 ± 17.16 years of them 58.25% were males. 2.9% patients had COVID-19-related symptoms and 97.1% were asymptomatic. All symptomatic patients tested positive for COVID-19 IgM antibody and RT-PCR. Among asymptomatic patients 23% had positive COVID-19 antibodies, of them 56.5%patients had positive RT-PCR. One HCW developed COVID-19 during the study. None of the included patients developed new onset of COVID-19 infection, two weeks after the procedure.

Conclusion
COVID-19 antibody test may be a reasonable preprocedural screening method for low-income countries and COVID-19 RT-PCR screening for symptomatic patients and those with positive COVID-19 antibody test.
A review of the essential concepts in diagnosis, therapy, and gender assignment in disorders of sexual development
Authors: Sarma Vivek Parameswara 
Published: February 2022

AbstractBackgroundThe aim of this article is to review the essential concepts, current terminologies and classification, management guidelines and the rationale of gender assignment in different types of differences/disorders of sexual development.Main bodyThe basics of the present understanding of normal sexual differentiation and psychosexual development were reviewed. The current guidelines, consensus statements along with recommendations in management of DSD were critically analyzed to formulate the review. The classification of DSD that is presently in vogue is presented in detail, with reference to old nomenclature. The individual DSD has been tabulated based on various differential characteristics. Two schemes for analysis of DSD types, based on clinical presentation, karyotype and endocrine profile has been proposed here. The risk of gonadal malignancy in different types of DSD is analyzed. The rationale of gender assignment, therapeutic options, and ethical dimension of treatment in DSD is reviewed in detail.ConclusionThe optimal management of different types of DSD in the present era requires the following considerations: (1) establishment of a precise diagnosis, employing the advances in genetic and endocrine evaluation. (2) A multidisciplinary team is required for the diagnosis, evaluation, gender assignment and follow-up of these children, and during their transition to adulthood. (3) Deeper understanding of the issues in psychosexual development in DSD is vital for therapy. (4) The patients and their families should be an integral part of the decision-making process. (5) Recommendations for gender assignment should be based upon the specific outcome data. (6) The relative rarity of DSD should prompt constitution of DSD registers, to record and share information, on national/international basis. (7) The formation of peer support groups is equally important. The recognition that each subject with DSD is unique and requires individualized therapy remains the most paramount.
WFS1 Gene–associated Diabetes Phenotypes and Identification of a Founder Mutation in Southern India
Authors: Chapla Aaron , Johnson Jabasteen , Korula Sophy , Mohan Nisha , Ahmed Anish , Varghese Deny , Rangasamy Parthiban , Ravichandran Lavanya , Jebasingh Felix , Kumar Agrawal Krishna , Somasundaram Noel , Hesarghatta Shyamasunder Asha , Mathai Sarah , Simon Anna , Jha Sujeet , Chowdry Subhankar , Venkatesan Radha , Raghupathy Palany , Thomas Nihal 
Published: February 2022

Abstract

Context
Wolfram syndrome (WFS) is a rare autosomal recessive disorder characterized by juvenile-onset diabetes, diabetes insipidus, optic atrophy, deafness, and progressive neurodegeneration. However, due to the progressive nature of the disease and a lack of complete clinical manifestations, a confirmed diagnosis of WFS at the time of onset of diabetes is a challenge.

Objective
With WFS1 rare heterozygous variants reported in diabetes, there is a need for comprehensive genetic screening strategies for the early diagnosis of WFS and delineating the phenotypic spectrum associated with the WFS1 gene variants in young-onset diabetes.

Methods
This case series of 11 patients who were positive for WFS1 variants were identified with next-generation sequencing (NGS)–based screening of 17 genemonogenic diabetes panel. These results were further confirmed with Sanger sequencing.

Results
9 out of 11 patients were homozygous for pathogenic/likely pathogenic variants in the WFS1 gene. Interestingly, 3 of these probands were positive for the novel WFS1 (NM_006005.3): c.1107_1108insA (p.Ala370Serfs*173) variant, and haplotype analysis suggested a founder effect in 3 families from Southern India. Additionally, we identified 2 patients with young-onset diabetes who were heterozygous for a likely pathogenic variant or a variant of uncertain significance in the WFS1 gene.

Conclusion
These results project the need for NGS-based parallel multigene testing as a tool for early diagnosis of WFS and identify heterozygous WFS1 variants implicated in young-onset diabetes.
Obesity Due to Steroid Receptor Coactivator-1 Deficiency Is Associated With Endocrine and Metabolic Abnormalities
Authors: Cacciottolo Tessa M , Henning Elana , Keogh Julia M , Bel Lassen Pierre , Lawler Katherine , Bounds Rebecca , Ahmed Rachel , Perdikari Aliki , Mendes de Oliveira Edson , Smith Miriam , Godfrey Edmund M , Johnson Elspeth , Hodson Leanne , Clément Karine , van der Klaauw Agatha A , Farooqi I Sadaf 
Published: February 2022

Abstract

Context
Genetic variants affecting the nuclear hormone receptor coactivator steroid receptor coactivator, SRC-1, have been identified in people with severe obesity and impair melanocortin signaling in cells and mice. As a result, obese patients with SRC-1 deficiency are being treated with a melanocortin 4 receptor agonist in clinical trials.

Objective
Here, our aim was to comprehensively describe and characterize the clinical phenotype of SRC-1 variant carriers to facilitate diagnosis and clinical management.

Methods
In genetic studies of 2462 people with severe obesity, we identified 23 rare heterozygous variants in SRC-1. We studied 29 adults and 18 children who were SRC-1 variant carriers and performed measurements of metabolic and endocrine function, liver imaging, and adipose tissue biopsies. Findings in adult SRC-1 variant carriers were compared to 30 age- and body mass index (BMI)-matched controls.

Results
The clinical spectrum of SRC-1 variant carriers included increased food intake in children, normal basal metabolic rate, multiple fractures with minimal trauma (40%), persistent diarrhea, partial thyroid hormone resistance, and menorrhagia. Compared to age-, sex-, and BMI-matched controls, adult SRC-1 variant carriers had more severe adipose tissue fibrosis (46.2% vs 7.1% respectively, P = .03) and a suggestion of increased liver fibrosis (5/13 cases vs 2/13 in controls, odds ratio = 3.4), although this was not statistically significant.

Conclusion
SRC-1 variant carriers exhibit hyperphagia in childhood, severe obesity, and clinical features of partial hormone resistance. The presence of adipose tissue fibrosis and hepatic fibrosis in young patients suggests that close monitoring for the early development of obesity-associated metabolic complications is warranted.
Approach to the Patient: “Utility of the Copeptin Assay”
Authors: Christ-Crain Mirjam , Refardt Julie , Winzeler Bettina 
Published: February 2022

Abstract
Copeptin derives from the same precursor peptide preprovasopressin as arginine vasopressin (AVP). The secretion of both peptides is stimulated by similar physiological processes, such as osmotic stimulation, hypovolemia, or stress. AVP is difficult to measure due to complex preanalytical requirements and due to technical difficulties. In the last years, copeptin was found to be a stable, sensitive, and simple to measure surrogate marker of AVP release. Different immunoassays exist to measure copeptin. The 2 assays which have most often be used in clinical studies are the original sandwich immunoluminometric assay and its automated immunofluorescent successor. In addition, various enzyme-linked immunosorbent assay have been developed. With the availability of the copeptin assay, the differential diagnosis of diabetes insipidus was recently revisited. The goal for this article is therefore to first review the physiology of copeptin, and second to describe its use as marker for the differential diagnosis of vasopressin-dependent fluid disorders, mainly diabetes insipidus but also hyper- and hyponatremia. Furthermore, we highlight the role of copeptin as prognostic marker in other acute and chronic diseases.
Performance of DHEAS as a Screening Test for Autonomous Cortisol Secretion in Adrenal Incidentalomas: A Prospective Study
Authors: Liu Meng-si , Lou Yuan , Chen Huan , Wang Yi-jie , Zhang Zi-wei , Li Ping , Zhu Da-long 
Published: February 2022

Abstract

Context
Autonomous cortisol secretion (ACS) affects up to 30% of patients with adrenal incidentalomas (AIs). The current guidelines for ACS diagnosis are not decisive. A lower dehydroepiandrosterone sulfate (DHEAS) level is a potential biomarker, but the evidence is conflicting.

Objective
This prospective study aimed to evaluate and validate the ACS screening and diagnostic accuracy of DHEAS.

Methods and patients
Recruited patients with AI were screened for adrenal medullary and cortisol hypersecretion. The diagnosis of ACS was based on a serum cortisol level ≥ 50 nmol/L following a 1-mg dexamethasone suppression test (DST) and a low-dose DST. Age- and sex-specific DHEAS ratios were also calculated.

Results
In the development cohort (45 ACS and 242 non-ACS patients), the areas under the receiver operator characteristic curves (AUCs) of DHEAS and the DHEAS ratio were 0.869 (95% CI 0.824-0.906) and 0.799 (95% CI 0.748-0.844), respectively. The optimal DHEAS cutoff for diagnosing ACS was 60 μg/dL, with a sensitivity of 75.6% (95% CI 60.5-87.1) and a specificity of 81.4% (95% CI 76.4-86.5). The midnight serum cortisol level had moderate diagnostic accuracy [AUC 0.875 (95% CI 0.831-0.911)]. Suppressed adrenocorticotropic hormone (≤2.2 pmol/L) had a lower sensitivity (55.6%), and the 24-hour urinary free cortisol lacked sensitivity and specificity [AUC 0.633 (95% CI 0.603-0.721)]. In the validation cohort (14 ACS and 45 non-ACS patients), the sensitivity and specificity of the optimized DHEAS cutoff were 71.4% (95% CI 41.9-91.6) and 82.2% (95% CI 68.0-92.0), respectively.

Conclusions
A single basal measurement of DHEAS is valuable for identifying ACS. Because of its stability and ease of use, the DHEAS level could be used as an ACS screening test.
Heterozygote Advantage of the Type II Deiodinase Thr92Ala Polymorphism on Intrahospital Mortality of COVID-19
Authors: de Lima Beltrão Fabyan Esberard , de Almeida Beltrão Daniele Carvalhal , Carvalhal Giulia , de Lima Beltrão Fabricia Elizabeth , de Souza Braga Filho Jair , de Brito Oliveira Jocyel , de Jesus Joice dos Santos , Machado Gabriel Jeferson Rodríguez , dos Santos Silva Hatilla , Teixeira Helena Mariana Pitangueira , Rodrigues Juliana Lopes , de Figueiredo Camila Alexandrina Viana , dos Santos Costa Ryan , Hecht Fabio , Bianco Antonio C , da Conceição Rodrigues Gonçalves Maria , Ramos Helton Estrela 
Published: February 2022

Abstract

Context
The type 2 deiodinase and its Thr92Ala-DIO2 polymorphism have been linked to clinical outcomes in acute lung injury and pulmonary fibrosis.

Objective
Our objectives were to evaluate were cumulative mortality during admission according to Thr92Ala-DIO2 polymorphism.

Methods
Here we conducted an observational, longitudinal, and prospective cohort study to investigate a possible association between the Thr92Ala-DIO2 polymorphism and intrahospital mortality from COVID-19 in adult patients admitted between June and August 2020. Blood biochemistry, thyroid function tests, length of stay, comorbidities, complications, and severity scores were also studied according to Thr92Ala-DIO2 polymorphism.

Results
In total, 220 consecutive patients (median age 62; 48-74 years) were stratified into 3 subgroups: Thr/Thr (n = 79), Thr/Ala (n = 119), and Ala/Ala (n = 23). While the overall mortality was 17.3%, the lethality was lower in Ala/Thr patients (12.6%) than in Thr/Thr patients (21.7%) or Ala/Ala patients (23%). The heterozygous genotype (Thr/Ala) was associated with a 47% reduced risk of intrahospital mortality whereas univariate and multivariate logistic regression adjusted for multiple covariates revealed a reduction that ranged from 51% to 66%. The association of the Thr/Ala genotype with better clinical outcomes was confirmed in a metanalysis of 5 studies, including the present one.

Conclusion
Here we provide evidence for a protective role played by Thr92Ala-DIO2 heterozygosity in patients with COVID-19. This protective effect follows an inheritance model known as overdominance, in which the phenotype of the heterozygote lies outside the phenotypical range of both homozygous.
A Novel Form of Familial Vasopressin Deficient Diabetes Insipidus Transmitted in an X-linked Recessive Manner
Authors: Habiby Reema , Bichet Daniel G , Arthus Marie-Francoise , Connaughton Dervia , Shril Shirlee , Mane Shrikant , Majmundar Amar J , Hildebrandt Friedhelm , Robertson Gary L 
Published: February 2022

Abstract

Context
Familial pituitary diabetes insipidus has been described only in an autosomal dominant or recessive mode of inheritance.

Objective
This work aims to determine the cause of a novel form of familial diabetes insipidus (DI) that is controlled by desmopressin therapy but segregates in an X-linked recessive manner.

Methods
Thirteen members from 3 generations of the kindred with familial DI were studied. Water intake, urine volume, urine osmolality, plasma osmolality, and plasma vasopressin were measured under basal conditions, during fluid deprivation, 3% saline infusion, and water loading. Magnetic resonance images of the posterior pituitary also were obtained. In affected males, the effects of desmopressin therapy and linkage of the DI to markers for chromosome Xq28 were determined. In addition, the genes encoding vasopressin, aquaporin-2, the AVPR2 receptor, and its flanking regions were sequenced.

Results
This study showed that 4 males from 3 generations of the kindred have DI that is due to a deficiency of vasopressin, is corrected by standard doses of desmopressin, and segregates with markers for the AVPR2 gene in Xq28. However, no mutations were found in AVPR2 or its highly conserved flanking regions. Exome sequencing confirmed these findings and also revealed no deleterious variants in the provasopressin and aquaporin-2 genes. The 4 obligate female carriers osmo-regulated vasopressin in the low normal range.

Conclusion
X-linked recessive transmission of DI can be due to a defect in either the secretion or the action of vasopressin. Other criteria are necessary to differentiate and manage the 2 disorders correctly.