bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial-derived metabolites as a risk factor of age-related cognitive decline and dementia
Authors: Connell Emily , Le Gall Gwenaelle , Pontifex Matthew G. , Sami Saber , Cryan John F. , Clarke Gerard , Müller Michael , Vauzour David 
Published: June 2022

AbstractA consequence of our progressively ageing global population is the increasing prevalence of worldwide age-related cognitive decline and dementia. In the absence of effective therapeutic interventions, identifying risk factors associated with cognitive decline becomes increasingly vital. Novel perspectives suggest that a dynamic bidirectional communication system between the gut, its microbiome, and the central nervous system, commonly referred to as the microbiota-gut-brain axis, may be a contributing factor for cognitive health and disease. However, the exact mechanisms remain undefined. Microbial-derived metabolites produced in the gut can cross the intestinal epithelial barrier, enter systemic circulation and trigger physiological responses both directly and indirectly affecting the central nervous system and its functions. Dysregulation of this system (i.e., dysbiosis) can modulate cytotoxic metabolite production, promote neuroinflammation and negatively impact cognition. In this review, we explore critical connections between microbial-derived metabolites (secondary bile acids, trimethylamine-N-oxide (TMAO), tryptophan derivatives and others) and their influence upon cognitive function and neurodegenerative disorders, with a particular interest in their less-explored role as risk factors of cognitive decline.
Spectrum of germline pathogenic variants using a targeted next generation sequencing panel and genotype-phenotype correlations in patients with suspected hereditary breast cancer at an academic medical centre in Pakistan
Authors: Akbar Fizza , Siddiqui Zahraa , Waheed Muhammad Talha , Ehsan Lubaina , Ali Syed Ibaad , Wiquar Hajra , Valimohammed Azmina Tajuddin , Khan Shaista , Vohra Lubna , Zeeshan Sana , Rashid Yasmin , Moosajee Munira , Jabbar Adnan Abdul , Zahir Muhammad Nauman , Zahid Naila , Soomro Rufina , Ullah Najeeb Niamat , Ahmad Imran , Haider Ghulam , Ansari Uzair , Rizvi Arjumand , Mehboobali Arif , Sattar Abida , Kirmani Salman 
Published: June 2022

Abstract
Background
Breast cancer is the most common malignancy in women, affecting over 1.5 million women every year, which accounts for the highest number of cancer-related deaths in women globally.
Hereditary breast cancer (HBC), an important subset of breast cancer, accounts for 5–10% of total cases. However, in Low Middle-Income Countries (LMICs), the population-specific risk of HBC in different ethnicities and the correlation with certain clinical characteristics remain unexplored.

Methods
Retrospective chart review of patients who visited the HBC clinic and proceeded with multi-gene panel testing from May 2017 to April 2020.
Descriptive and inferential statistics were used to analyze clinical characteristics of patients. Fisher’s exact, Pearson’s chi-squared tests and Logistic regression analysis were used for categorical variables and Wilcoxon rank-sum test were used for quantitative variables. For comparison between two independent groups, Mann-Whitney test was performed. Results were considered significant at a p value of < 0.05.

Results
Out of 273 patients, 22% tested positive, 37% had a VUS and 41% had a negative genetic test result. Fifty-five percent of the positive patients had pathogenic variants in either BRCA1 or BRCA2, while the remaining positive results were attributed to other genes. Patients with a positive result had a younger age at diagnosis compared to those having a VUS and a negative result; median age 37.5 years, IQR (Interquartile range) (31.5–48). Additionally, patients with triple negative breast cancer (TNBC) were almost 3 times more likely to have a positive result (OR = 2.79, CI = 1.42–5.48 p = 0.003). Of all patients with positive results, 25% of patients had a negative family history of breast and/or related cancers.

Conclusions
In our HBC clinic, we observed that our rate of positive results is comparable, yet at the higher end of the range which is reported in other populations. The importance of expanded, multi-gene panel testing is highlighted by the fact that almost half of the patients had pathogenic or likely pathogenic variants in genes other than BRCA1/2, and that our test positivity rate would have only been 12.8% if only BRCA1/2 testing was done. As the database expands and protocol-driven referrals are made across the country, our insight about the genetic architecture of HBC in our population will continue to increase.
Fluconazole in hypercalciuric patients with increased 1,25(OH)2D levels: the prospective, randomized, placebo-controlled, double-blind FLUCOLITH trial
Authors: Bertholet-Thomas Aurélia , Portefaix Aurélie , Flammier Sacha , Dhelens Carole , Subtil Fabien , Dubourg Laurence , Laudy Valérie , Le Bouar Myrtille , Boussaha Inesse , Ndiaye Marietou , Molin Arnaud , Lemoine Sandrine , Bacchetta Justine 
Published: June 2022

Abstract
Background
Hypercalciuria is one of the most frequent metabolic disorders associated with nephrolithiasis and/or nephrocalcinosis possibly leading to chronic kidney disease (CKD) and bone complications in adults. Orphan diseases with different underlying primary pathophysiology share inappropriately increased 1,25(OH)2D levels and hypercalciuria, e.g., hypersensitivity to vitamin D and renal phosphate wasting. Their management is challenging, typically based on hyperhydration and dietary advice.
The antifungal azoles are known to inhibit the 1α-hydroxylase and therefore decrease 1,25(OH)2D levels; they are commonly used, with well described pharmacokinetic and tolerability data. Fluconazole has been successfully reported to reduce calciuria in patients with CYP24A1 or SLC34A3 mutations, with no safety warnings. Thus, based on these case reports, we hypothesize that fluconazole is effective to decrease and normalize calciuria in patients with hypercalciuria and increased 1,25(OH)2D levels.

Methods
The FLUCOLITH trial is a prospective, interventional, randomized in parallel groups (1:1), placebo-controlled, double-blind trial. A total of 60 patients (10–60 years) with nephrolithiasis and/or nephrocalcinosis history, hypercalciuria (> 0.1 mmol/kg/day), increased 1,25(OH)2D levels (> 150 pmol/L), and 25-OH-D levels >20 nmol/L will be included. Inclusions will be performed only from mid-September to the beginning of February to avoid bias due to sunlight-induced vitamin D synthesis. The primary endpoint will be the proportion of patients with normalization of 24-h calciuria between baseline and 16 weeks, or with a relative decrease of at least 30% of 24-h calciuria in patients who still display at W16 a 24-h hypercalciuria.

Discussion
The current challenge is to propose an efficient treatment to patients with hypercalciuria and increased 1,25(OH)2D levels in order to prevent later complications and notably CKD that can ultimately lead to end-stage renal disease. Based on improvement of knowledge in phosphate/calcium metabolism, pathophysiology and genetics, the “off-label” use of fluconazole was recently reported to be useful in hypercalciuric patients with increased 1,25(OH)2D levels. Thus, the FLUCOLITH study is a unique opportunity to develop a new indication of a well-known and not expensive drug in orphan renal diseases, the ultimate objective being the secondary prevention of CKD worsening in these patients.

Trial registration
ClinicalTrials.gov NCT04495608. Registered on July 23, 2020.
Qatar Diabetes Mobile Application Trial (QDMAT): an open-label randomised controlled trial to examine the impact of using a mobile application to improve diabetes care in type 2 diabetes mellitus—a study protocol
Authors: Suleiman Noor , Alkasem Meis , Al Amer Zaina , Salameh Obada , Al-Thani Noora , Hamad Mohammad Khair , Baagar Khaled , Abdalhakam Ibrahem , Othman Manal , Dughmosh Ragae , Al-Mohanadi Dabia , Al Sanousi Ali , Bashir Mohammed , Chagoury Odette , Taheri Shahrad , Abou-Samra Abdul-Badi 
Published: June 2022

Abstract
Background
Mobile health (mHealth) is increasingly advocated for diabetes management. It is unclear if mobile applications are effective in improving glycaemic control, clinical outcomes, quality of life and overall patient satisfaction in patients with type 2 diabetes (T2DM). A new mobile application was specifically built for people with T2DM with the help of the local expertise. The objective of the study was to evaluate the effectiveness of the mobile app.

Methods
The planned study is an ongoing open-label randomised controlled trial in which adults living with T2DM treated with insulin will be randomised 1:1 to the use of this diabetes application versus current standard care. The primary outcome will be the difference in mean HbA1c from baseline to 6 months. Other outcome measures include anthropometric measures, hypoglycaemic events, medication adjustments, number of clinical interactions and missed appointments and patient perceptions of their disease and diabetes self-management. The study will randomise 180 subjects for assessment of the primary outcome.

Discussion
We hypothesise that the diabetes-specific mobile application will improve glycaemic control, increase patient empowerment for self-management of diabetes and improve interaction between patients and healthcare providers. If the Qatar Diabetes Mobile Application Trial (QDMAT) demonstrates this, it will inform clinical services for the future self-management of T2DM.

Trial registration
ClinicalTrials.gov Identifier: NCT03998267. Registered on 26 June 2019
Effect of hospital-at-home vs. traditional brick-and-mortar hospital care in acutely ill adults: study protocol for a pragmatic randomized controlled trial
Authors: Yao Xiaoxi , Paulson Margaret , Maniaci Michael J. , Dunn Ajani N. , Nelson Chad R. , Behnken Emma M. , Hart Melissa S. , Sangaralingham Lindsey R. , Inselman Shealeigh A. , Lampman Michelle A. , Dunlay Shannon M. , Dowdy Sean C. , Habermann Elizabeth B. 
Published: June 2022

AbstractBackgroundDelivering acute hospital care to patients at home might reduce costs and improve patient experience. Mayo Clinic’s Advanced Care at Home (ACH) program is a novel virtual hybrid model of “Hospital at Home.” This pragmatic randomized controlled non-inferiority trial aims to compare two acute care delivery models: ACH vs. traditional brick-and-mortar hospital care in acutely ill patients.MethodsWe aim to enroll 360 acutely ill adult patients (≥18 years) who are admitted to three hospitals in Arizona, Florida, and Wisconsin, two of which are academic medical centers and one is a community-based practice. The eligibility criteria will follow what is used in routine practice determined by local clinical teams, including clinical stability, social stability, health insurance plans, and zip codes. Patients will be randomized 1:1 to ACH or traditional inpatient care, stratified by site. The primary outcome is a composite outcome of all-cause mortality and 30-day readmission. Secondary outcomes include individual outcomes in the composite endpoint, fall with injury, medication errors, emergency room visit, transfer to intensive care unit (ICU), cost, the number of days alive out of hospital, and patient-reported quality of life. A mixed-methods study will be conducted with patients, clinicians, and other staff to investigate their experience.DiscussionThe pragmatic trial will examine a novel virtual hybrid model for delivering high-acuity medical care at home. The findings will inform patient selection and future large-scale implementation.Trial registrationClinicalTrials.govNCT05212077. Registered on 27 January 2022
Implementation of patient-reported outcomes for symptom management in oncology practice through the SIMPRO research consortium: a protocol for a pragmatic type II hybrid effectiveness-implementation multi-center cluster-randomized stepped wedge trial
Authors: Hassett Michael J. , Wong Sandra , Osarogiagbon Raymond U. , Bian Jessica , Dizon Don S. , Jenkins Hannah Hazard , Uno Hajime , Cronin Christine , Schrag Deborah ,   SIMPRO Co-Investigators
Published: June 2022

Abstract
Background
Many cancer patients experience high symptom burden. Healthcare in the USA is reactive, not proactive, and doctor-patient communication is often suboptimal. As a result, symptomatic patients may suffer between clinic visits. In research settings, systematic assessment of electronic patient-reported outcomes (ePROs), coupled with clinical responses to severe symptoms, has eased this symptom burden, improved health-related quality of life, reduced acute care needs, and extended survival. Implementing ePRO-based symptom management programs in routine care is challenging. To study methods to overcome the implementation gap and improve symptom control for cancer patients, the National Cancer Institute created the Cancer-Moonshot funded Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) Consortium.

Methods
Symptom Management IMplementation of Patient Reported Outcomes in Oncology (SIMPRO) is one of three research centers that make up the IMPACT Consortium. SIMPRO, a multi-disciplinary team of investigators from six US health systems, seeks to develop, test, and integrate an electronic symptom management program (eSyM) for medical oncology and surgery patients into the Epic electronic health record (EHR) system and associated patient portal. eSyM supports real-time symptom tracking for patients, automated clinician alerts for severe symptoms, and specialized reports to facilitate population management. To rigorously evaluate its impact, eSyM is deployed through a pragmatic stepped wedge cluster-randomized trial. The primary study outcome is the occurrence of an emergency department treat-and-release event within 30 days of starting chemotherapy or being discharged following surgery. Secondary outcomes include hospitalization rates, chemotherapy use (time to initiation and duration of therapy), and patient quality of life and satisfaction. As a type II hybrid effectiveness-implementation study, facilitators and barriers to implementation are assessed throughout the project.

Discussion
Creating and deploying eSyM requires collaboration between dozens of staff across diverse health systems, dedicated engagement of patient advocates, and robust support from Epic. This trial will evaluate eSyM in routine care settings across academic and community-based healthcare systems serving patients in rural and metropolitan locations. This trial’s pragmatic design will promote generalizable results about the uptake, acceptability, and impact of an EHR-integrated, ePRO-based symptom management program.

Trial registration

ClinicalTrials.gov NCT03850912. Registered on February 22, 2019. Last updated on November 9, 2021.
Doxycycline post-exposure prophylaxis for prevention of sexually transmitted infections among Kenyan women using HIV pre-exposure prophylaxis: study protocol for an open-label randomized trial
Authors: Stewart Jenell , Bukusi Elizabeth , Sesay Fredericka A. , Oware Kevin , Donnell Deborah , Soge Olusegun O. , Celum Connie , Odoyo Josephine , Kwena Zachary A. , Scoville Caitlin W. , Violette Lauren R. , Morrison Susan , Simoni Jane , McClelland R. Scott , Barnabas Ruanne , Gandhi Monica , Baeten Jared M. 
Published: June 2022

Abstract

Background
Women in Africa face disproportionate risk of human immunodeficiency virus (HIV) acquisition, accounting for more than half of new infections in Africa and similarly face a disproportionate burden of sexually transmitted infections (STIs). Very high STI prevalence is being observed globally, especially among people taking pre-exposure prophylaxis (PrEP) for HIV prevention. Doxycycline post-exposure prophylaxis (dPEP) has been proposed as an STI prevention strategy to reduce chlamydia, syphilis, and possibly gonorrhea, and trials are ongoing among cisgender men who have sex with men (MSM) and transgender women who are taking PrEP in high-income settings. We designed and describe here the first open-label trial to determine the effectiveness of dPEP to reduce STI incidence among cisgender women.

Methods
We are conducting an open-label 1:1 randomized trial of dPEP versus standard of care (STI screening and treatment and risk-reduction counseling without dPEP) among 446 Kenyan women aged ≥ 18 and ≤ 30 years old women taking PrEP. Women are followed for 12 months, with quarterly STI testing, treatment, and adherence counseling. The primary trial outcome will be the combined incidence of Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum, compared between the randomized groups. We will also assess dPEP acceptability, tolerability, safety, impact on sexual behavior, adherence, and occurrence of antimicrobial resistance (AMR) in N. gonorrhoeae and C. trachomatis isolates. Finally, we will estimate cost per incident STI case and complications averted accounting for nonadherence and benefits relative AMR or side effects.

Discussion
The results of this trial may have immediate implications for the global epidemic of STIs and sexual health. If effective, dPEP could put STI prevention into women’s hands. While dPEP may be able to prevent STIs, it carries important risks that could counter its benefits; global debate about the balance of these potential risks and benefits requires data to inform policy and implementation and our study aims to fill this gap.

Trial registration

ClinicalTrials.gov NCT04050540.
Hormone therapy and the decreased risk of dementia in women with depression: a population-based cohort study
Authors: Kim Hyewon , Yoo Juhwan , Han Kyungdo , Lee Dong-Yun , Fava Maurizio , Mischoulon David , Jeon Hong Jin 
Published: June 2022

Abstract
Background
The literature has shown depression to be associated with an increased risk of dementia. In addition, hormone therapy can be a responsive treatment option for a certain type of depression. In this study, we examined the association between hormone therapy, including lifetime oral contraceptive (OC) use, and hormone replacement therapy (HRT) after menopause with the occurrence of dementia among female patients with depression.

Methods
The South Korean national claims data from January 1, 2005, to December 31, 2018, was used. Female subjects aged 40 years or older with depression were included in the analyses. Information on hormone therapy was identified from health examination data and followed up for the occurrence of dementia during the average follow-up period of 7.72 years.

Results
Among 209,588 subjects, 23,555 were diagnosed with Alzheimer’s disease (AD) and 3023 with vascular dementia (VD). Lifetime OC usage was associated with a decreased risk of AD (OC use for < 1 year: HR, 0.92 [95% CI, 0.88–0.97]; OC use for ≥ 1 year: HR, 0.89 [95% CI, 0.84–0.94]), and HRT after menopause was associated with a decreased risk of AD (HRT for < 2 years: HR, 0.84 [95% CI, 0.79–0.89]; HRT for 2–5 years: HR, 0.80 [95% CI, 0.74–0.88]; and HRT for ≥ 5 years : HR, 0.78 [95% CI, 0.71–0.85]) and VD (HRT < 2 years: HR, 0.82 [95% CI, 0.71–0.96]; HRT for 2–5 years: HR, 0.81 [95% CI, 0.64–1.02]; and HRT for ≥ 5 years: HR, 0.61 [95% CI, 0.47–0.79]).

Conclusions
In this nationwide cohort study, lifetime OC use was associated with a decreased risk of AD, and HRT after menopause was associated with a decreased risk of AD and VD among female patients with depression. However, further studies are needed to establish causality.
Genetics of cerebral malaria: pathogenesis, biomarkers and emerging therapeutic interventions
Authors: Nortey Lydia Nkuah , Anning Alberta Serwah , Nakotey Gideon Kwesi , Ussif Abdala Mumuni , Opoku Yeboah Kwaku , Osei Silas Acheampong , Aboagye Benjamin , Ghartey-Kwansah George 
Published: June 2022

AbstractBackgroundCerebral malaria (CM) is a preeminent cause of severe disease and premature deaths in Sub-Saharan Africa, where an estimated 90% of cases occur. The key features of CM are a deep, unarousable coma that persists for longer than 1 h in patients with peripheralPlasmodium falciparumand no other explanation for encephalopathy. Significant research efforts on CM in the last few decades have focused on unravelling the molecular underpinnings of the disease pathogenesis and the identification of potential targets for therapeutic or pharmacologic intervention. These efforts have been greatly aided by the generation and study of mouse models of CM, which have provided great insights into key events of CM pathogenesis, revealed an interesting interplay of host versus parasite factors that determine the progression of malaria to severe disease and exposed possible targets for therapeutic intervention in severe disease.Main BodyThis paper reviews our current understanding of the pathogenic and immunologic factors involved in CM. We present the current view of the roles of certain gene products e.g., the var gene, ABCA-1, ICAM-1, TNF-alpha, CD-36, PfEMP-1 and G6PD, in CM pathogenesis. We also present alterations in the blood–brain barrier as a consequence of disease proliferation as well as complicated host and parasite interactions, including the T-cell immune reaction, reduced deformation of erythrocytes and cytoadherence. We further looked at recent advances in cerebral malaria treatment interventions by emphasizing on biomarkers, new diagnostic tools and emerging therapeutic options.ConclusionFinally, we discuss how the current understanding of some of these pathogenic and immunologic factors could inform the development of novel therapeutic interventions to fight CM.
Fixed points of single-valued and multi-valued mappings in sb-metric spaces
Authors: Tassaddiq Asifa , Kanwal Shazia , Perveen Saba , Srivastava Rekha 
Published: June 2022

AbstractIn this paper, we have established some fixed point theorems in the context of strong b-metric spaces. For this purpose, Ciric type contraction for single-valued mapping and Nadler’s type Banach and Chatterjea contractions for set-valued mappings are applied to obtain fixed point and common fixed points. A simple and different technique has been used to obtain the results. Our results unify, extend and generalize the existence of corresponding present and conventional results existing in the literature of fixed point theory.