bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alteration in gut mycobiota of patients with polycystic ovary syndrome
Authors: Chen Ke , Geng Huafeng , Liu Junbao , Ye Cong 
Published: September 2023

ABSTRACT

Polycystic ovary syndrome (PCOS) is a serious disease characterized by high androgen, insulin resistance (IR), hyperglycemia, and obesity, leading to infertility. The gut mycobiota has been reported to evolve in metabolic diseases including obesity, hyperglycemia, and fatty liver. However, little is known about the gut mycobiota and PCOS. In the current study, we recruited 17 PCOS patients and 17 age-matched healthy controls for community structure and functional analysis of the gut mycobiota. The results showed that PCOS patients have reduced diversity and richness of the gut microbiota compared with healthy controls. β-Diversity analysis showed that the community structure of the gut microbiota of patients with PCOS was significantly different from healthy controls. At the phylum level, PCOS patients have reduced
Basidiomycota
and increased
Ascomycota
compared with healthy controls. At the family level, the higher relative abundance of
Saccharomycetaceae
and lower
Trichosporonaceae
and
Ascomycota_unclassified
were detected in PCOS patients than in healthy controls. At the genus level, different microbial compositions were also observed between PCOS patients and healthy controls. In addition, PICRUSt2 showed that patients with PCOS have different microbial functions in the gut compared with healthy controls. LEfSe indicated that
Saccharomyces
and
Lentinula
were enriched in the fecal samples of PCOS patients, while
Aspergillus
was depleted compared with healthy controls. Our finding indicates that PCOS patients have different community structures and functions of the gut mycobiota, which provides new insight into PCOS pathogenesis and intervention.

IMPORTANCE
It was found that intestinal fungi as well as serum metabolites in PCOS patients were significantly different from those in healthy subjects. However, no studies have been done to show exactly which fungus interacts with which bacteria in humans or which fungus acts alone. As fungal research progresses, it will be possible to fill this gap.
Regulatory response to a hybrid ancestral nitrogenase in
Azotobacter vinelandii
Authors: Rivier Alex J. , Myers Kevin S. , Garcia Amanda K. , Sobol Morgan S. , Kaçar Betül 
Published: September 2023

ABSTRACT

Biological nitrogen fixation, the microbial reduction of atmospheric nitrogen to bioavailable ammonia, represents both a major limitation on biological productivity and a highly desirable engineering target for synthetic biology. However, the engineering of nitrogen fixation requires an integrated understanding of how the gene regulatory dynamics of host diazotrophs respond across sequence-function space of its central catalytic metalloenzyme, nitrogenase. Here, we interrogate this relationship by analyzing the transcriptome of
Azotobacter vinelandii
engineered with a phylogenetically inferred ancestral nitrogenase protein variant. The engineered strain exhibits reduced cellular nitrogenase activity but recovers wild-type growth rates following an extended lag period. We find that expression of genes within the immediate nitrogen fixation network is resilient to the introduced nitrogenase sequence-level perturbations. Rather the sustained physiological compatibility with the ancestral nitrogenase variant is accompanied by reduced expression of genes that support trace metal and electron resource allocation to nitrogenase. Our results spotlight gene expression changes in cellular processes adjacent to nitrogen fixation as productive engineering considerations to improve compatibility between remodeled nitrogenase proteins and engineered host diazotrophs.

IMPORTANCE

Azotobacter vinelandii
is a key model bacterium for the study of biological nitrogen fixation, an important metabolic process catalyzed by nitrogenase enzymes. Here, we demonstrate that compatibilities between engineered
A. vinelandii
strains and nitrogenase variants can be modulated at the regulatory level. The engineered strain studied here responds by adjusting the expression of proteins involved in cellular processes adjacent to nitrogen fixation, rather than that of nitrogenase proteins themselves. These insights can inform future strategies to transfer nitrogenase variants to non-native hosts.
Rare cause of persistent hypocalcaemia in infancy due to PTH gene mutation
Authors: Khadse Savita , Takalikar Vrushali Satish , Ghildiyal Radha , Shah Nikhil 
Published: September 2023

Hypocalcaemia is a frequently encountered electrolyte abnormality in neonates and it is mostly transient. However, persistent hypocalcaemia can point towards an endocrine abnormality like hypoparathyroidism, which is usually due to genetic disorders like DiGeorge and Kearns Sayre syndrome or due to mutations of genes like GCM2, CaSR and PTH.Our patient was a female child, who presented with hypocalcaemic convulsions in the neonatal period. On laboratory assessment, serum phosphate levels were noted to be high along with inappropriately low parathyroid hormone (PTH) levels. The child was diagnosed to have hypoparathyroidism and was started on oral calcium and 1,25-dihydroxycholecalciferol supplements to which she responded well. However, the child was lost to follow-up and was readmitted with hypocalcaemic convulsions in infancy. Clinical exome analysis done was diagnostic of homozygous PTH gene mutation. This case demonstrates a rare form of congenital isolated hypoparathyroidism with no other syndromic associations.
Deep learning detection of diabetic retinopathy in Scotland’s diabetic eye screening programme
Authors: Fleming Alan D , Mellor Joseph , McGurnaghan Stuart J , Blackbourn Luke A K , Goatman Keith A , Styles Caroline , Storkey Amos J , McKeigue Paul M , Colhoun Helen M 
Published: September 2023

Background/Aims
Support vector machine-based automated grading (known as iGradingM) has been shown to be safe, cost-effective and robust in the diabetic retinopathy (DR) screening (DES) programme in Scotland. It triages screening episodes as gradable with no DR versus manual grading required. The study aim was to develop a deep learning-based autograder using images and gradings from DES and to compare its performance with that of iGradingM.

Methods
Retinal images, quality assurance (QA) data and routine DR grades were obtained from national datasets in 179 944 patients for years 2006–2016. QA grades were available for 744 images. We developed a deep learning-based algorithm to detect whether either eye contained ungradable images or any DR. The sensitivity and specificity were evaluated against consensus QA grades and routine grades.

Results
Images used in QA which were ungradable or with DR were detected by deep learning with better specificity compared with manual graders (p<0.001) and with iGradingM (p<0.001) at the same sensitivities. Any DR according to the DES final grade was detected with 89.19% (270 392/303 154) sensitivity and 77.41% (500 945/647 158) specificity. Observable disease and referable disease were detected with sensitivities of 96.58% (16 613/17 201) and 98.48% (22 600/22 948), respectively. Overall, 43.84% of screening episodes would require manual grading.

Conclusion
A deep learning-based system for DR grading was evaluated in QA data and images from 11 years in 50% of people attending a national DR screening programme. The system could reduce the manual grading workload at the same sensitivity compared with the current automated grading system.
Uncovering heterogeneous cardiometabolic risk profiles in US adults: the role of social and behavioral determinants of health
Authors: Ding Qinglan , Lu Yuan , Herrin Jeph , Zhang Tianyi , Marrero David G 
Published: September 2023

IntroductionSocial and behavioral determinants of health (SBDH) have been linked to diabetes risk, but their role in explaining variations in cardiometabolic risk across race/ethnicity in US adults is unclear. This study aimed to classify adults into distinct cardiometabolic risk subgroups using SBDH and clinically measured metabolic risk factors, while comparing their associations with undiagnosed diabetes and pre-diabetes by race/ethnicity.Research design and methodsWe analyzed data from 38,476 US adults without prior diabetes diagnosis from the National Health and Nutrition Examination Survey (NHANES) 1999–2018. The k-prototypes clustering algorithm was used to identify subgroups based on 16 SBDH and 13 metabolic risk factors. Each participant was classified as having no diabetes, pre-diabetes or undiagnosed diabetes using contemporaneous laboratory data. Logistic regression was used to assess associations between subgroups and diabetes status, focusing on differences by race/ethnicity.ResultsThree subgroups were identified: cluster 1, primarily middle-aged adults with high rates of smoking, alcohol use, short sleep duration, and low diet quality; cluster 2, mostly young non-white adults with low income, low health insurance coverage, and limited healthcare access; and cluster 3, mostly older males who were the least physically active, but with high insurance coverage and healthcare access. Compared with cluster 2, adjusted ORs (95% CI) for undiagnosed diabetes were 14.9 (10.9, 20.2) in cluster 3 and 3.7 (2.8, 4.8) in cluster 1. Clusters 1 and 3 (vs cluster 2) had high odds of pre-diabetes, with ORs of 1.8 (1.6, 1.9) and 2.1 (1.8, 2.4), respectively. Race/ethnicity was found to modify the relationship between identified subgroups and pre-diabetes risk.ConclusionsSelf-reported SBDH combined with metabolic factors can be used to classify adults into subgroups with distinct cardiometabolic risk profiles. This approach may help identify individuals who would benefit from screening for diabetes and pre-diabetes and potentially suggest effective prevention strategies.
Long-course chemoradiation plus concurrent/sequential PD-1 blockade as neoadjuvant treatment for MMR-status-unscreened locally advanced rectal cancer: protocol of a multicentre, phase 2, randomised controlled trial (the POLAR-STAR trial)
Authors: Pang Kai , Yang Yun , Tian Dan , Zeng Na , Cao Shun , Ling Shen , Gao Jiale , Zhao Pengfei , Wang Hao , Kong Yuanyuan , Zhang Jie , Chen Guangyong , Deng Wei , Bai Zhigang , Jin Lan , Wu Guoju , Zhu Danyang , Wang Yue , Zhou Jiaolin , Wu Bin , Lin Guole , Xiao Yi , Gao Zhidong , Ye Yingjiang , Wang Xin , Li Ang , Han Jiagang , Yao Hongwei , Yang Yingchi , Zhang Zhongtao 
Published: September 2023

IntroductionRecent preclinical studies have discovered unique synergism between radiotherapy and immune checkpoint inhibitors, which has already brought significant survival benefit in lung cancer. In locally advanced rectal cancer (LARC), neoadjuvant radiotherapy plus immune checkpoint inhibitors have also achieved surprisingly high pathological complete response (pCR) rates even in proficient mismatch-repair patients. As existing researches are all phase 2, single-cohort trials, we aim to conduct a randomised, controlled trial to further clarify the efficacy and safety of this novel combination therapy.Methods and analysisEligible patients with LARC are randomised to three arms (two experiment arms, one control arm). Patients in all arms receive long-course radiotherapy plus concurrent capecitabine as neoadjuvant therapy, as well as radical surgery. Distinguishingly, patients in arm 1 also receive anti-PD-1 (Programmed Death 1) treatment starting at Day 8 of radiation (concurrent plan), and patients in arm 2 receive anti-PD-1 treatment starting 2 weeks after completion of radiation (sequential plan). Tislelizumab (anti-PD-1) is scheduled to be administered at 200 mg each time for three consecutive times, with 3-week intervals. Randomisation is stratified by different participating centres, with a block size of 6. The primary endpoint is pCR rate, and secondary endpoints include neoadjuvant-treatment-related adverse event rate, as well as disease-free and overall survival rates at 2, 3 and 5 years postoperation. Data will be analysed with an intention-to-treat approach.Ethics and disseminationThis protocol has been approved by the institutional ethical committee of Beijing Friendship Hospital (the primary centre) with an identifying serial number of 2022-P2-050-01. Before publication to peer-reviewed journals, data of this research will be stored in a specially developed clinical trial database.Trial registration numberNCT05245474.
Efficacy and safety of drug therapy for the prevention and treatment of chemotherapy-induced peripheral neuropathy: a protocol for a systematic review and network meta-analysis
Authors: Sato Miki Takenaka , Hasegawa Takeshi , Noma Hisashi , Sugita Hideki , Ota Erika 
Published: September 2023

IntroductionChemotherapy-induced peripheral neuropathy (CIPN) is one of the most common dose-limiting side effects of chemotherapeutic drugs. Numerous clinical trials of various targeted drugs for the prevention or treatment of CIPN have been conducted; however, previous systematic reviews with direct comparisons have failed to demonstrate the efficacy of these drugs in the prevention or treatment of CIPN. In addition, no systematic reviews have indirectly compared CIPN prevention and treatment. This article describes a protocol for evaluating the efficacy and safety of drug therapy for the prevention and treatment of CIPN. The results of the proposed systematic review with network meta-analysis (NMA) will provide new insights into the prevention and treatment of CIPN.Methods and analysisWe will conduct a literature search in MEDLINE, PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov to find relevant articles published through January 2023. We will include studies that investigated the efficacy and safety of vitamin B12, goshajinkigan, non-steroidal anti-inflammatory analgesics, opioids, calcium and magnesium, antidepressants and anticonvulsants on CIPN. Two authors will individually screen the retrieved reports and review the full text based on the selection criteria. The primary outcome is the incidence and severity of CIPN. The risk of bias will be assessed using V.2.0 of the Cochrane risk-of-bias tool. We will apply a frequentist random-effects NMA model to pool effect sizes across trials using risk ratios and mean differences with their 95% CIs. Competing interventions will be ranked using the surface under cumulative ranking probabilities. Heterogeneity will be assessed using the heterogeneity variance τ2, Cochran’s Q test and I² statistic.Ethics and disseminationThis review does not require ethical approval. The research will be published in a peer-reviewed journal.PROSPERO registration numberCRD42022371829.
Development of practice-based quality indicators for the primary care of older adults: a RAND/UCLA Appropriateness Method study protocol
Authors: Correia Rebecca H , Siu Henry Yu-Hin , Vanstone Meredith , Jones Aaron , Gopaul Aquila , Costa Andrew P 
Published: September 2023

IntroductionOlder adults have high rates of primary care utilisation, and quality primary care has the potential to address their complex medical needs. Family physicians have different levels of knowledge and skills in caring for older patients, which may influence the quality of care delivery and resulting health outcomes. In this study, we aim to establish consensus on practice-based metrics that characterise quality of care for older primary care patients and can be examined using secondary, administrative data.Methods and analysisWe describe a two-round RAND/UCLA Appropriateness Method (RAM) study to assess the consensus of a technical expert panel. We will recruit pan-Canadian experts who demonstrate excellence in clinical practice or scholarship related to the primary care of older adults. A literature review will generate a candidate list of practice-based quality indicators. The first round aims to evaluate the appropriateness and importance of candidate indicators through an online questionnaire. We will then develop technical definitions for each endorsed indicator using ICES data holdings. Panellists will offer feedback on the technical definitions in a virtual synchronous meeting and provide ratings on the same criteria in a second questionnaire.Ethics and disseminationOur study has been approved by the Hamilton Integrated Research Ethics Board (Project ID #15545). Findings will be disseminated via manuscripts, presentations and the lead author’s thesis.Trial registration numberISRCTN17074347
Characteristics of programmes designed to link community-dwelling older adults in high-income countries from community to clinical sectors: a scoping review protocol
Authors: Gofine Miriam , Laynor Gregory , Schoenthaler Antoinette 
Published: September 2023

IntroductionResearch on effectively navigating older adults into primary care is urgently needed. Community–clinic linkage models (CCLMs) aim to improve population health by linking the health and community sectors in order to improve patients’ access to healthcare and, ultimately, population health. However, research on community-based points of entry linking adults with untreated medical needsintothe healthcare sector is nascent. CCLMs implemented for the general adult population are not necessarily accessible to older adults. Given the recency of the CCLM literature and the seeming rarity of CCLM interventions designed for older adults, it is appropriate to employ scoping review methodology in order to generate a comprehensive review of the available information on this topic. This protocol will inform a scoping review that reviews characteristics of community-based programmes that link older adults with the healthcare sector.Methods and analysisThe present protocol was developed as per JBI Evidence Synthesis best practice guidance and reporting items for the development of scoping review protocols. The proposed scoping review will follow Levac and colleagues’ update to Arksey and O’Malley’s scoping review methodology. Healthcare access at the system and individual levels will be operationalised in data extraction and analysis in accordance with Levesque and colleagues’ Conceptual Framework of Access to Health. The protocol complies with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Beginning in August 2023 or later, citation databases (AgeLine (Ebsco); CINAHL Complete; MEDLINE (PubMed); Scopus Advanced (Elsevier); Social Services Abstracts (ProQuest); Web of Science Core Collection (Clarivate)) and grey literature (Google; American Public Health Association Annual Meeting Conference Proceedings; SIREN Evidence & Resource Library) will be searched.Ethics and disseminationThe authors plan to disseminate their findings in conference proceedings and publication in a peer-reviewed journal and deposit extracted data in the Figshare depository. The study does not require Institutional Review Board approval.Registration detailsProtocol registered in Open Science Framework (DOIhttps://doi.org/10.17605/OSF.IO/2EF9D).
Development and validation of a product acceptability questionnaire for intranasal Q-Griffithsin COVID-19 prophylaxis (SPRAY PAL)
Authors: Cash Elizabeth , Deitz Kailyn , Potts Kevin L , Nabeta Henry W , Zahin Maryam , Rai Shesh N , Dryden Gerald W , Palmer Kenneth E 
Published: September 2023

ObjectivesPatient experiences are critical when determining the acceptability of novel interventional pharmaceuticals. Here, we report the development and validation of a product acceptability questionnaire (SPRAY PAL) assessing feasibility, acceptability and tolerability of an intranasal Q-Griffithsin (Q-GRFT) drug product designed for COVID-19 prophylaxis.DesignSPRAY PAL validation was undertaken as part of an ongoing phase 1 clinical trial designed to test the safety, pharmacokinetics and tolerability of intranasally administered Q-GRFT for the prevention of SARS-CoV-2 infection.SettingThe phase 1 clinical trial took place at a University Outpatient Clinical Trials Unit from November 2021 to September 2023.ParticipantsThe initial SPRAY PAL questionnaire was piloted among healthy volunteers ages 25 to 55 in phase 1a of the clinical trial (N=18) and revised for administration in phase 1b for participants ages 24–59 (N=22).ResultsSpearman correlations tested convergent and discriminant validity. Internal consistency was assessed using Cronbach’s alpha, and test–retest reliability was assessed using intraclass correlation coefficients of responses collected from three repeated questionnaire administrations. The initial version demonstrated excellent internal consistency. The revised version demonstrated very good internal consistency after removal of one item (alpha=0.739). Excellent test–retest reliability (intraclass coefficient=0.927) and adequate convergent (r’s=0.208–0.774) and discriminant (r’s=0.123–0.392) validity were achieved. Subscales adequately distinguished between the constructs of acceptability, feasibility and tolerability.ConclusionsThe SPRAY PAL product acceptability questionnaire is a valid and reliable patient-reported outcomes measure that can be considered a credible tool for assessing patient-reported information about product acceptability, feasibility of use, tolerability of product and side effects and cost of product for novel intranasal drug formulations. The SPRAY PAL is generalisable, and items may be readily adapted to assess other intranasal formulations.Trial registration numbersNCT05122260andNCT05437029.
Intravenous versus oral hydration to reduce the risk of postcontrast acute kidney injury after intravenous contrast-enhanced CT in patients with severe chronic kidney disease (ENRICH): a study protocol for a single-centre, parallel-group, open-labelled non-inferiority randomised controlled trial in Denmark
Authors: Ravn Emil Johannes , Hasific Selma , Thomassen Mads , Hjortebjerg Rikke , Bach Laursen Kristian , Diederichsen Axel , Bistrup Claus , Øvrehus Kristian A 
Published: September 2023

IntroductionContrast-enhanced CT (CECT) is widely used for diagnostic purposes. The use of contrast medium carries a risk for postcontrast acute kidney injury (PC-AKI), especially in patients with AKI or chronic kidney disease (CKD). Current guidelines recommend prophylactic intravenous hydration to prevent PC-AKI in high-risk patients. Oral hydration is non-inferior to intravenous hydration in patients with moderate CKD, but it has not been evaluated in high-risk patients.Methods and analysisThe ENRICH trial will enrol 254 patients with estimated glomerular filtration rate ≤30 mL/min/1.73 m2undergoing intravenous CECT, who are block randomised (2-4-2) with stratification for CKD stage, diabetes status, and indication for referral to prophylactic treatment with oral or intravenous hydration. PC-AKI is defined as an absolute increase in SCr of >0.3 mg/dL or >1.5 from baseline at 2–5 days. Renal function will also be evaluated <90 days, <7 days and 1–3 days before intravenous CECT, and 25–40 days after intravenous CECT. Secondary outcomes include dialysis, renal adverse events, hospitalisation due to hydration-related or contrast-related sequelae, and all-cause mortality ≤30 days postcontrast. Pre- and postcontrast plasma and urinary biomarkers will be evaluated for diagnostic and prognostic accuracy of the primary and secondary outcomes.Ethics and disseminationOral hydration is patient-friendly and less costly compared with intravenous hydration. If oral hydration is non-inferior to intravenous hydration in high-risk patients, it could be implemented as new hydration strategy, which will facilitate the clinical diagnosing of elective patients with severe CKD without unnecessary resource utilisation. The protocol is approved by the Regional Scientific Ethical Committee for Southern Denmark (S-20210126), and the Data Protection Agency (21/66779). The study is conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported in international peer-reviewed journals.Trial registration numberNCT05283512.