bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of MDR1 Gene Polymorphisms in Human Male Infertility: A Meta-Analysis
Authors: Sohail Anam , Arshad Adina , Tariq Tamjeed , Bibi Ayesha , Aslam Shaista , Irfan Muhammad
Published: April 2023

The present meta-analysis is performed to determine the association of C1236T and C3435T polymorphisms in the MDR1 gene. Google Scholar, PubMed, and Science Direct were searched. A total of 47 studies were retrieved, of which only three case–control studies, consisting of 490 cases and 423 controls, met the selection criteria. Odds ratios (ORs) for MDR1 C1236T were as follows: Allelic model (T vs. C): OR = 1.06 [0.83, 1.35]; Additive model (TT vs. CC): OR = 0.91 [0.53, 1.56]; Dominant model (TT+CT vs. CC): OR = 0.83 [0.55, 1.24]; and Recessive model (TT vs. CT+CC): OR = 1.43 [0.95, 2.17]. However, for MDR1 C3435T: Allelic model (T vs. C): OR = 1.06 [0.83, 1.35]; Additive model (TT vs. CC): OR = 1.18 [0.75, 1.88]; Dominant model (TT+CT vs. CC): OR = 1.42 [0.99, 2.04]; and Recessive model (TT vs. CT+CC): OR = 0.90 [0.61, 1.33]. None of the four models presented a significant association of either polymorphism with the risk of infertility in men ( p >.05). The present study indicates that MDR1 gene polymorphisms might not be a risk factor for male infertility. Further studies with a larger sample size are needed to be conducted to confirm the findings of the present study.
Internationally-national schools: A critical review of this developing sector and the frameworks that define international schools
Authors: Pearce Sarah
Published: April 2023

Across the world, the international school sector is changing at a rapid pace, having an impact on all facets of international schools, from curriculum to clientele. This article describes an emerging concept from this sector that I have termed the internationally-national school, borne from the nationally affiliated schools that currently exist within the sector that have adapted and evolved. It seeks to contribute to the discourse on international schools and the typologies used to categorise them. In order to embed this concept as a subsection of international schools, this article critically analyses three established frameworks currently in use to classify international schools and positions the internationally-national school within each framework. From this analysis, I conclude that internationally-national schools should be a recognised part of the international school landscape and that there is a need for an update to some of these frameworks as they lack the flexibility required to keep pace with the everchanging sector.
Etiology, Classification, Diagnostics, and Conservative Management of Osteochondral Lesions of the Talus. 2023 Recommendations of the Working Group “Clinical Tissue Regeneration” of the German Society of Orthopedics and Traumatology
Authors: Walther Markus , Gottschalk Oliver , Madry Henning , Müller Peter E. , Steinwachs Matthias , Niemeyer Philipp , Niethammer Thomas R. , Tischer Thomas , Petersen Jan , Feil Roman , Fickert Stefan , Schewe Bernhard , Hörterer Hubert , Ruhnau Klaus , Becher Christoph , Klos Kajetan , Plaass Christian , Rolauffs Bernd , Behrens Peter , Spahn Gunter , Welsch Götz , Angele Peter , Ahrend Marc-Daniel , Kasten Philip , Erggelet Christoph , Ettinger Sarah , Günther Daniel , Körner Daniel , Aurich Matthias
Published: April 2023

The working group, “Clinical Tissue Regeneration” of the German Society of Orthopedics and Traumatology (DGOU) issues this paper to update their guidelines.

Methods

Peer-reviewed literature was analyzed regarding different topics relevant to osteochondral lesions of the talus (OLTs) treatment. This process concluded with a statement for each topic reflecting the best scientific evidence available for a particular diagnostic or therapeutic concept, including the grade of recommendation. Besides the scientific evidence, all group members rated the statements to identify possible gaps between literature and current clinical practice.

Conclusion

In patients with minimal symptoms, OLT progression to ankle osteoarthritis is unlikely. Risk factors for progression are the depth of the lesion on MRI, subchondral cyst formation, and the extent of bone marrow edema. Conservative management is the adaptation of activities to the performance of the ankle joint. A follow-up imaging after 12 months helps not to miss any progression. It is impossible to estimate the probability of success of conservative management from initial symptoms and imaging. Cast immobilization is an option in OLTs in children, with a success rate of approximately 50%, although complete healing, estimated from imaging, is rare. In adults, improvement by conservative management ranges between 45% and 59%. Rest and restrictions for sports activities seem to be more successful than immobilization. Intra-articular injections of hyaluronic acid and platelet-rich plasma can improve pain and functional scores for more than 6 months. If 3 months of conservative management does not improve symptoms, surgery can be recommended.
A cross-sectional study on reliability and quality of YouTube® videos related to hallux valgus and evaluation of newly developed hallux valgus-specific survey tool
Authors: Batar Suat , Söylemez Mehmet Salih , Kemah Bahattin , Cepni Serdar Kamil
Published: April 2023

Objective

Previous studies have reported low quality and reliability on YouTube videos about various medical issues including videos related to hallux valgus (HV) treatment. Therefore, we aimed to evaluate the reliability and quality of YouTube videos on HV and develop a new HV-specific survey tool that physicians, surgeons, and the medical industry can use to create high-quality videos.

Methods

Videos viewed over 10,000 times were included in the study. We used the Journal of the American Medical Association (JAMA) benchmark criteria, global quality score (GQS), DISCERN tool, and new HV-specific survey criteria (HVSSC) developed by us to evaluate the quality, educational utility and reliability of the videos, the popularity of which was assessed using the Video Power Index (VPI) and view ratio (VR).

Results

Fifty-two videos were included in this study. Fifteen videos (28.8%) were posted by medical companies producing surgical implants and orthopedic products, 20 (38.5%) by nonsurgical physicians, and 16 (30.8%) by surgeons. The HVSSC indicated that the quality, educational value, and reliability of only 5 (9.6%) videos were adequate. Videos posted by physicians and surgeons tended to be more popular ( p = 0.047 and 0.043). Although no correlation was detected among the DISCERN, JAMA, and GQS scores, or between the VR and VPI, we found correlations of the HVSSC score with the number of views and the VR ( p = 0.374 and p = 0.006, respectively). A good correlation was detected among the DISCERN, GQS, and HVSSC classifications (rho = 0.770, 0.853, and 0.831, respectively, p = 0.001).

Conclusions

The reliability of HV-related videos on YouTube is low for professionals and patients. The HVSSC can be used to evaluate the quality, educational value, and reliability of videos.
The Longitudinal Association Between Posttraumatic Stress Disorder, Emotion Dysregulation, and Postmigration Stressors Among Refugees
Authors: Specker Philippa , Liddell Belinda J. , O’Donnell Meaghan , Bryant Richard A. , Mau Vicki , McMahon Tadgh , Byrow Yulisha , Nickerson Angela
Published: April 2023

Although emotion dysregulation has been robustly associated with posttraumatic stress disorder (PTSD), there is relatively little understanding of this process in refugees. Specifically, longitudinal methodology has not been used to examine the relationship between emotion dysregulation and PTSD among refugees. In this study, we investigated the temporal relationship between emotion dysregulation, postmigration stressors, and PTSD clusters (reexperiencing, avoidance, negative alterations in mood and cognition [NAMC], and hyperarousal) from the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders among a community sample of refugees ( N = 1,081) over a 2-year period. Random intercept cross-lagged panel analysis found that emotion dysregulation was antecedent to within-persons increases in reexperiencing and NAMC symptoms over time and bidirectionally associated with hyperarousal and postmigration stressors. In addition, postmigration stressors were antecedent to within-persons increases in reexperiencing, avoidance, and NAMC and bidirectionally associated with hyperarousal symptoms. Findings provide novel evidence in support of postmigration stressors and emotion dysregulation as mechanisms maintaining PTSD and highlight the potential utility of tailoring interventions to address these factors.
New data on minerals with the GIS framework-type structure: gismondine-Sr from the Bellerberg volcano, Germany, and amicite and Ba-rich gismondine from the Hatrurim Complex, Israel
Authors: Skrzyńska Katarzyna , Cametti Georgia , Juroszek Rafał , Schӓfer Christof , Galuskina Irina
Published: April 2023

Gismondine-Sr, recently discovered in the Hatrurim Complex in Israel, has been recognised in a xenolith sample from the Bellerberg volcano in Germany. The empirical crystal-chemical formula indicates elevated K content: (Sr1.74Ca1.05Ba0.09K1.56Na0.49)Σ4.93[Al7.98Si8.06O32]⋅9.62H2O. Additionally, Ba-rich gismondine and amicite have been found in the low-temperature mineral association of the pyrometamorphic rock from the Hatrurim Complex. The Raman spectra of the studied zeolites and the crystal structure of gismondine-Sr from the second occurrence are presented. A review of zeolites with GIS framework-type structure leads to the following conclusions: (1) garronite-Na and gobbinsite are equivalent and constitute a solid solution with garronite-Ca; (2) gismondine-Ca, -Sr, and amicite belong to one mineral series; (3) two zeolites series with different R-factors (defined as Si/(Si+Al+Fe)) can be distinguished within GIS topology: the garronite series (R > 0.6) including garronite-Ca and gobbinsite, with general formula (MyD0.5(x–y))[AlxSi(16–x)O32]⋅nH2O, where M and D refer to monovalent and divalent cations, respectively; and the gismondine series, including amicite, gismondine-Sr and gismondine-Ca, with R ≈ 0.5, and the general formula (MyD0.5(8–y))[Al8Si8O32]⋅nH2O. The Raman band between 475 cm–1 and 485 cm–1 is distinctive for the garronite series, whereas the band around 460 cm–1 is characteristic of the gismondine series. On the basis of these findings, a revision of GIS zeolites nomenclature is suggested.
A gene regulatory network inference model based on pseudo-siamese network
Authors: Wang Qian , Guo Maozu , Chen Jian , Duan Ran
Published: April 2023

Motivation

Gene regulatory networks (GRNs) arise from the intricate interactions between transcription factors (TFs) and their target genes during the growth and development of organisms. The inference of GRNs can unveil the underlying gene interactions in living systems and facilitate the investigation of the relationship between gene expression patterns and phenotypic traits. Although several machine-learning models have been proposed for inferring GRNs from single-cell RNA sequencing (scRNA-seq) data, some of these models, such as Boolean and tree-based networks, suffer from sensitivity to noise and may encounter difficulties in handling the high noise and dimensionality of actual scRNA-seq data, as well as the sparse nature of gene regulation relationships. Thus, inferring large-scale information from GRNs remains a formidable challenge.

Results

This study proposes a multilevel, multi-structure framework called a pseudo-Siamese GRN (PSGRN) for inferring large-scale GRNs from time-series expression datasets. Based on the pseudo-Siamese network, we applied a gated recurrent unit to capture the time features of each TF and target matrix and learn the spatial features of the matrices after merging by applying the DenseNet framework. Finally, we applied a sigmoid function to evaluate interactions. We constructed two maize sub-datasets, including gene expression levels and GRNs, using existing open-source maize multi-omics data and compared them to other GRN inference methods, including GENIE3, GRNBoost2, nonlinear ordinary differential equations, CNNC, and DGRNS. Our results show that PSGRN outperforms state-of-the-art methods. This study proposed a new framework: a PSGRN that allows GRNs to be inferred from scRNA-seq data, elucidating the temporal and spatial features of TFs and their target genes. The results show the model’s robustness and generalization, laying a theoretical foundation for maize genotype-phenotype associations with implications for breeding work.
Effects of probiotic/synbiotic supplementation on body weight in patients with diabetes: a systematic review and meta-analyses of randomized-controlled trials
Authors: Soltani Sepideh , Ashoori Marziyeh , Dehghani Fereshteh , Meshkini Fatemeh , Clayton Zachary Stephen , Abdollahi Shima
Published: April 2023

Objective

The aim of the present study was to assess the effect of probiotic/synbiotic supplementation on anthropometric measures in adults with diabetes, independent of body weight.

Methods

PubMed, Scopus, Web of Sciences and the Cochrane Library were searched for randomized controlled trials (RCTs) up until December 14, 2022. The effect sizes were pooled using an inverse-variance random-effects model. The methodological quality of studies as well as the quality of evidence was assessed using standard tools.

Results

Thirty-two RCTs met the established inclusion criteria. Overall, compared with the respective control groups, probiotic/synbiotic supplementation resulted in a significant reduction in body weight (weighted mean difference [WMD]: -0.50 kg; 95% CI: -0.83, -0.17; I2 = 79.8%, n = 27 studies]), body mass index (WMD: -0.24 kg/m2; 95% CI: -0.39, -0.09; I2 = 85.7%, n = 30 studies), and waist circumference (WMD: -0.90 cm; 95% CI: -1.13, -0.52; I2 = 0%, n = 11 studies). However, hip circumference and waist to hip ratio were not significantly improved.

Conclusions

Our analysis revealed that probiotic/synbiotic supplementation may assist with weight management in patients with diabetes, especially when consumed at higher doses, in younger adults, and in participants with obesity. However, more studies are needed to elucidate the anti-obesity effects of specific strains of probiotics/synbiotics.
Three-dimensional facial swelling evaluation of piezo-electric vs conventional drilling bur surgery of impacted lower third molar: a randomized clinical trial
Authors: Caputo A. , Rubino E. , Marcianò A. , Peditto M. , Bellocchio A. M. , Nucera R. , Oteri G.
Published: April 2023

Background

Among the post-surgical complications of lower wisdom teeth surgery, swelling is considered by patients one of the most impairing, with both social and biological influences and impacting patients' quality of life. Aim of the study was to evaluate the swelling following the osteotomy when performed with drilling burs versus piezo-electric instruments in the mandibular impacted third molar extraction, using a facial reconstruction software.

Materials and methods

A randomized, split-mouth, single-blind study was conducted on patients, ranging between 18 and 40 years of age, requiring lower third molars extraction and referred at the Oral Surgery Unit of the School of Dentistry of the University of Messina. Twenty-two patients were recruited during an 8 months period according to the following criteria: good general health conditions; bilateral, symmetrical, impacted third molars; no use of medication that would influence or alter wound healing; no temporomandibular joint disorder history; no smoking. All patients underwent bilateral surgical removal. For each patient, a facial scan was obtained prior to the surgical procedures. The two extractions were conducted performing, in a randomized way, osteotomy with rotatory burs or use of piezo surgical instruments. Facial scans were repeated at 3 and 7 days after the surgical procedures. Volumetric differences were calculated via superimposition using a dedicated software. The data obtained were processed using paired t-test.

Results

The results obtained from our study showed no significant differences between two groups regarding post-operative swelling. To the best of our knowledge, this study represents the first experience of using an objective method that can be reproducible on the collection of patients' clinical parameters.

Conclusions

The 3D digital analysis, in the evaluation of facial swelling, is a technique of simple application, objective, reproducible, reliable, decreasing the variables of error.

Based on these data, it is possible to conclude that piezo surgery is a safe way for performing the osteotomies during third molar surgery. However, regarding the post-operative swelling, it does not show an advantage over classical rotary instruments.

Trial registration

Registered on ClinicalTrials.gov (ID: NCT05488028, on 04/08/2022).

Approved by Ethical Committee of Messina: (ID 01–2020, on 27/04/2020).
Extended-release metformin improves cognitive impairment in frail older women with hypertension and diabetes: preliminary results from the LEOPARDESS Study
Authors: Mone Pasquale , Martinelli Giuseppe , Lucariello Angela , Leo Anna Luisa , Marro Anna , De Gennaro Stefano , Marzocco Stefania , Moriello Divina , Frullone Salvatore , Cobellis Luigi , Santulli Gaetano
Published: April 2023

Background

Women have a high risk of frailty independently of age and menopause state. Diabetes and hypertension increase the risk of frailty and cognitive impairment. Metformin has been employed in post-menopausal women and some reports have shown encouraging effects in terms of attenuated frailty. However, the impact on cognitive performance of a recently introduced extended-release formulation of metformin has never been explored.

Methods

We studied consecutive frail hypertensive and diabetic older women presenting at the ASL (local health authority of the Italian Ministry of Health) Avellino, Italy, from June 2021 to August 2022, who were treated or not with extended-release metformin. We included a control group of frail older males with diabetes and hypertension treated with extended-release metformin and a control group of frail older women with diabetes and hypertension treated with regular metformin.

Results

A total of 145 patients successfully completed the study. At the end of the 6-month follow-up, we observed a significantly different cognitive performance compared to baseline in the group of frail women treated with extended-release metformin (p: 0.007). Then, we compared the follow-up groups and we observed significant differences between frail women treated vs. untreated (p: 0.041), between treated frail women and treated frail men (p: 0.016), and between women treated with extended-release metformin vs. women treated with regular metformin (p: 0.048). We confirmed the crucial role of extended-release metformin applying a multivariable logistic analysis to adjust for potential confounders.

Conclusions

We evidenced, for the first time to the best of our knowledge, the favorable effects on cognitive impairment of extended-release metformin in frail women with diabetes and hypertension.
Cerebral venous sinus thrombosis associated with SRA-negative heparin-induced thrombocytopenia: case report
Authors: Silva Floyd D. , Burnett Allison E. , Padmanabhan Anand , Rollins-Raval Marian A. , Splinter Noah P. , Desai Masoom J.
Published: April 2023

Background

There are very few documented reports in literature of cerebral venous sinus thrombosis (CVST) caused by immune-mediated heparin-induced thrombocytopenia (HIT). Further, there are very few reports of false negative serotonin release assays (SRAs) when testing for immune-mediated HIT.

Case presentation

We present a case of a 60- year-old male with recent unfractionated heparin administration for venous thromboembolism prophylaxis, an elevated 4T score of 5 and acute CVST in which immune-mediated HIT was suspected. The enzyme-linked immunosorbent assay (ELISA) screening assay was positive for PF4 antibodies and subsequent reflexive SRA testing was negative. However, given the clinical picture, a false-negative SRA was suspected (and eventually confirmed), prompting use of the alternative PF4-dependent p-selectin expression assay (PEA) which was confirmed to be positive. The patient was successfully managed with a bivalirudin infusion and eventually transitioned to apixaban.

Conclusion

It is uncommon for immune-mediated HIT with thrombosis to manifest as CVST. Similarly, false-negative SRA is uncommon in immune-mediated HIT. Take-away lessons from our case report include considering HIT in CVST patients with an elevated 4T score and considering the entire clinical picture and degree of suspicion for HIT when interpreting negative HIT testing results. The PEA, in conjunction with the 4Ts score, may be considered as an alternate diagnostic assay for HIT.
The health and economic burden of musculoskeletal disorders in Belgium from 2013 to 2018
Authors: Gorasso Vanessa , Van der Heyden Johan , De Pauw Robby , Pelgrims Ingrid , De Clercq Eva M. , De Ridder Karin , Vandevijvere Stefanie , Vansteelandt Stijn , Vaes Bert , De Smedt Delphine , Devleesschauwer Brecht
Published: April 2023

Introduction

Low back pain (LBP), neck pain (NKP), osteoarthritis (OST) and rheumatoid arthritis (RHE) are among the musculoskeletal (MSK) disorders causing the greatest disability in terms of Years Lived with Disability. The current study aims to analyze the health and economic impact of these MSK disorders in Belgium, providing a summary of morbidity and mortality outcomes from 2013 to 2018, as well as direct and indirect costs from 2013 to 2017.

Methods

The health burden of LBP, NKP, OST and RHE in Belgium from 2013 to 2018 was summarized in terms of prevalence and disability-adjusted life years (DALY) using data from the Belgian health interview surveys (BHIS), the INTEGO database (Belgian registration network for general practitioners) and the Global Burden of Diseases study 2019. The economic burden included estimates of direct medical costs and indirect costs, measured by cost of work absenteeism. For this purpose, data of the respondents to the BHIS-2013 were linked with the national health insurance data (intermutualistic agency [IMA] database) 2013–2017.

Results

In 2018, 2.5 million Belgians were affected by at least one MSK disorder. OST represented the disorder with the highest number of cases for both men and women, followed by LBP. In the same year, MSK disorders contributed to a total of 180,746 DALYs for female and 116,063 DALYs for men. LBP appeared to be the largest contributor to the health burden of MSK. Having at least one MSK disorder costed on average 3 billion € in medical expenses and 2 billion € in indirect costs per year, with LBP being the most costly.

Conclusion

MSK disorders represent a major health and economic burden in Belgium. As their burden will probably continue to increase in the future, acting on the risk factors associated to these disorders is crucial to mitigate both the health and economic burden.
Overlap between birth trauma and mistreatment: a qualitative analysis exploring American clinician perspectives on patient birth experiences
Authors: Salter Cynthia , Wint Kristina , Burke Jessica , Chang Judy C. , Documet Patricia , Kaselitz Elizabeth , Mendez Dara
Published: April 2023

Introduction

Research exploring the mistreatment of birthing people in the United States is emerging rapidly within the context of increasingly poor maternal health outcomes that include unacceptable racial disparities. Previous research has explored overlap between psychological birth trauma and mistreatment using patient descriptions of birth experiences, but no previous studies have explored these issues from the perspectives of clinicians. The aim of this study was to explore whether maternity care providers’ descriptions of patient birth trauma overlap with categories of mistreatment from a globally accepted typology.

Methods

Content analysis was performed on a qualitative data set of 28 semi-structured interviews about patient birth trauma, completed in 2018–2019 with U.S. maternity care clinicians, including obstetricians, family physicians, midwives and labor/delivery nurses. The interviews were part of a larger study exploring maternity clinician perspectives and experiences of patient birth trauma. For this analysis Krippendorff’s method of categoric distinction was used, with categories from a globally recognized typology of maternity patient mistreatment.

Results

Clinicians’ descriptions of their experiences with patient birth trauma mapped onto all seven mistreatment categories, although no interview questions specifically asked about mistreatment. In more than 30 hours of interviews, transcribed to more than 800 pages, the word mistreatment appears only once, suggesting that some healthcare providers may use the phrase “birth trauma” as a euphemism to describe mistreatment. Eighteen of 28 interviews included at least one description that fit into a mistreatment category. “Failure to meet professional standards of care” was the category with the most mapped clinician statements, followed by “Stigma and discrimination” and “Poor rapport between women and providers.”

Conclusions

This study contributes new insight into maternity clinicians’ conceptualization of patient trauma and how their descriptions of birth trauma overlap with mistreatment. Clinicians implicitly connected mistreatment with some patient experiences of birth trauma, even when they were not specifically asked about mistreatment. Findings point to a need for further research into mistreatment, including routinized “everyday care” that may include mistreatment, particularly for marginalized and historically excluded birthing people. Future research also must explore the potential role of mistreatment in poor and inequitable U.S. birth outcomes.
A cross-sectional analysis of psychosocial and structural barriers and facilitators associated with PrEP use among a sample of transgender women in Chicago, IL
Authors: Kuhns Lisa M. , Perloff Judy , Johnson Amy K. , Paul Josie Lynne , Pleasant Kevin , Evans Kaiji , Denson Damian J. , Gelaude Deborah J. , Bessler Patricia A. , Diskin Rose , Cervantes Marbella , Garofalo Robert , Hotton Anna L.
Published: April 2023

Background

Expanding pre-exposure prophylaxis (PrEP) among transgender women in the United States is an important strategy to meet national HIV prevention goals, however self-reported use of PrEP is low in this group.

Methods

This study reports the findings of a cross-sectional analysis of the relationship of barriers as well as facilitators to recent PrEP use among transgender women enrolled in an evaluation of the TransLife Care project (Chicago, Illinois), a structural intervention designed to meet basic needs. We computed multivariable prevalence ratios for barriers, facilitators and recent PrEP use, controlling for demographics.

Results

Findings suggest that psychosocial and structural barriers, including moderate/high alcohol use, stimulant use, and history of incarceration were all positively associated with recent PrEP use among urban transgender women. In addition, a psychosocial facilitator, gender affirmation, was positively associated with recent PrEP use, while, while collective self-esteem, a was negatively associated with it. Finally, common indications for PrEP have high sensitivity, but low specificity and predictive value for identifying those on PrEP.

Conclusion

We conclude that despite a large gap in PrEP use among those with indications, individuals experiencing psychosocial and structural barriers are more likely to use PrEP, and facilitators, such as psychological sense of affirmed gender may support its use.

Trial registration

N/A.
Lung-gut axis of microbiome alterations following co-exposure to ultrafine carbon black and ozone
Authors: Mazumder Md Habibul Hasan , Gandhi Jasleen , Majumder Nairrita , Wang Lei , Cumming Robert Ian , Stradtman Sydney , Velayutham Murugesan , Hathaway Quincy A. , Shannahan Jonathan , Hu Gangqing , Nurkiewicz Timothy R. , Tighe Robert M. , Kelley Eric E. , Hussain Salik
Published: April 2023

Background

Microbial dysbiosis is a potential mediator of air pollution-induced adverse outcomes. However, a systemic comparison of the lung and gut microbiome alterations and lung-gut axis following air pollution exposure is scant. In this study, we exposed male C57BL/6J mice to inhaled air, CB (10 mg/m3), O3 (2 ppm) or CB + O3 mixture for 3 h/day for either one day or four consecutive days and were euthanized 24 h post last exposure. The lung and gut microbiome were quantified by 16 s sequencing.

Results

Multiple CB + O3 exposures induced an increase in the lung inflammatory cells (neutrophils, eosinophils and B lymphocytes), reduced absolute bacterial load in the lungs and increased load in the gut. CB + O3 exposure was more potent as it decreased lung microbiome alpha diversity just after a single exposure. CB + O3 co-exposure uniquely increased Clostridiaceae and Prevotellaceae in the lungs. Serum short chain fatty acids (SCFA) (acetate and propionate) were increased significantly only after CB + O3 co-exposure. A significant increase in SCFA producing bacterial families (Ruminococcaceae, Lachnospiraceae, and Eubacterium) were also observed in the gut after multiple exposures. Co-exposure induced significant alterations in the gut derived metabolite receptors/mediator (Gcg, Glp-1r, Cck) mRNA expression. Oxidative stress related mRNA expression in lungs, and oxidant levels in the BALF, serum and gut significantly increased after CB + O3 exposures.

Conclusion

Our study confirms distinct gut and lung microbiome alterations after CB + O3 inhalation co-exposure and indicate a potential homeostatic shift in the gut microbiome to counter deleterious impacts of environmental exposures on metabolic system.
Health related quality of life of patients following mechanical valve replacement surgery for rheumatic mitral stenosis in Tanzania
Authors: Mutagaywa Reuben K , Cramer Maarten J , Chillo Pilly , Khamis Ramadhan H , Boniface Respicious , Muhozya Anjela , Barongo Aileen , Byomuganyizi Moses , Kwesigabo Gideon , Kamuhabwa Appolinary , Nyangasa Bashir , Kisenge Peter , Chamuleau Steven
Published: April 2023

Background

The assessment of outcomes of interventions based on the patient’s perspective using patient-reported outcome measures (PROMs) has been increasingly highlighted in clinical practice. However, health related quality of life (HRQoL), one of the common constructs measured by PROMs remain unknown among patients after heart valve replacement (HVR) in Tanzania.

Objectives

To assess the HRQoL amongst patients operated on for rheumatic mitral stenosis at Jakaya Kikwete Cardiac Institute (JKCI).

Methods

A prospective study of patients operated on due to rheumatic mitral stenosis at JKCI from January 2020 to April 2021 was undertaken. The HRQoL was assessed by using the MacNew questionnaire, addressing three domains (physical, emotional, and social function); the score ranges from 0 to 7. We categorized HRQoL as low (mean score ≤ 4.9), moderate (5–6) and high (> 6). We analysed several sociodemographic and clinical variables for HRQoL.

Results

Out of 54 patients, there were 34 females and 20 males. Their mean (± SD) age was 37.98 (± 12.58) years. The reliability of translated Kiswahili version of MacNew was good. The mean (± SD) global scores were 3.47 ± 0.59, 4.88 ± 0.71 and 6.14 ± 0.50 preoperatively, at 3 months and 6 months respectively (p-values < 0.001 preoperatively vs. 3 months, preoperatively vs. 6 months and at 3 months vs. 6 months). The median of individual mean difference HRQoL score pre-operatively and at 6 months was 2.67. The preoperative and 6 months mean difference HRQoL scores were higher among patients with vs. without atrial fibrillation (2.95 ± 0.59 vs. 2.45 ± 0.53, p = 0.003) and those on anticoagulants (preoperatively) vs. not on anticoagulants (3.14 ± 0.58 vs. 2.57 ± 0.57, 0.009). The mean difference HRQoL scores were similar for sociodemographic and other clinical parameters, including those with stroke vs. without stroke.

Conclusion

Six months after HVR the overall MacNew HRQoL scores improved markedly. This improvement in HRQoL was regardless of the presence of comorbidities (e.g. stroke and atrial fibrillation) which underscores the importance of considering valvular surgery if they fit the criteria. Clinicians and researchers in low-resource settings should collaborate to promote the utilization of PROMs in the routine care of patients.
Proteostasis failure exacerbates neuronal circuit dysfunction and sleep impairments in Alzheimer’s disease
Authors: Morrone Christopher Daniel , Raghuraman Radha , Hussaini S. Abid , Yu Wai Haung
Published: April 2023

Failed proteostasis is a well-documented feature of Alzheimer’s disease, particularly, reduced protein degradation and clearance. However, the contribution of failed proteostasis to neuronal circuit dysfunction is an emerging concept in neurodegenerative research and will prove critical in understanding cognitive decline. Our objective is to convey Alzheimer’s disease progression with the growing evidence for a bidirectional relationship of sleep disruption and proteostasis failure. Proteostasis dysfunction and tauopathy in Alzheimer’s disease disrupts neurons that regulate the sleep–wake cycle, which presents behavior as impaired slow wave and rapid eye movement sleep patterns. Subsequent sleep loss further impairs protein clearance. Sleep loss is a defined feature seen early in many neurodegenerative disorders and contributes to memory impairments in Alzheimer’s disease. Canonical pathological hallmarks, β-amyloid, and tau, directly disrupt sleep, and neurodegeneration of locus coeruleus, hippocampal and hypothalamic neurons from tau proteinopathy causes disruption of the neuronal circuitry of sleep. Acting in a positive-feedback-loop, sleep loss and circadian rhythm disruption then increase spread of β-amyloid and tau, through impairments of proteasome, autophagy, unfolded protein response and glymphatic clearance. This phenomenon extends beyond β-amyloid and tau, with interactions of sleep impairment with the homeostasis of TDP-43, α-synuclein, FUS, and huntingtin proteins, implicating sleep loss as an important consideration in an array of neurodegenerative diseases and in cases of mixed neuropathology. Critically, the dynamics of this interaction in the neurodegenerative environment are not fully elucidated and are deserving of further discussion and research. Finally, we propose sleep-enhancing therapeutics as potential interventions for promoting healthy proteostasis, including β-amyloid and tau clearance, mechanistically linking these processes. With further clinical and preclinical research, we propose this dynamic interaction as a diagnostic and therapeutic framework, informing precise single- and combinatorial-treatments for Alzheimer’s disease and other brain disorders.

Graphical Abstract
Statistical analyses of ordinal outcomes in randomised controlled trials: protocol for a scoping review
Authors: Selman Chris J. , Lee Katherine J. , Whitehead Clare L. , Manley Brett J. , Mahar Robert K.
Published: April 2023

Introduction

Randomised controlled trials (RCTs) aim to assess the effect of one (or more) unproven health interventions relative to other reference interventions. RCTs sometimes use an ordinal outcome, which is an endpoint that comprises of multiple, monotonically ordered categories that are not necessarily separated by a quantifiable distance. Ordinal outcomes are appealing in clinical settings as specific disease states can represent meaningful categories that may be of clinical importance to researchers. Ordinal outcomes can also retain information and increase statistical power compared to dichotomised outcomes and can allow multiple clinical outcomes to be comprised in a single endpoint. Target parameters for ordinal outcomes in RCTs may vary depending on the nature of the research question, the modelling assumptions and the expertise of the data analyst.

The aim of this scoping review is to systematically describe the use of ordinal outcomes in contemporary RCTs. Specifically, we aim to:

$$\bullet$$∙Identify which target parameters are of interest in trials that use an ordinal outcome, and whether these parameters are explicitly defined.

$$\bullet$$∙Describe how ordinal outcomes are analysed in RCTs to estimate a treatment effect.

$$\bullet$$∙Describe whether RCTs that use an ordinal outcome adequately report key methodological aspects specific to the analysis of the ordinal outcome.

Results from this review will outline the current state of practice of the use of ordinal outcomes in RCTs. Ways to improve the analysis and reporting of ordinal outcomes in RCTs will be discussed.

Methods and analysis

We will review RCTs that are published in the top four medical journals (British Medical Journal,New England Journal of Medicine,The Lancet and theJournal of the American Medical Association) between 1 January 2012 and 31 July 2022 that use an ordinal outcome as either a primary or a secondary outcome. The review will identify articles through a PubMed-specific search strategy. Our review will adhere to guidelines for scoping reviews as described in the PRISMA-ScR checklist. The study characteristics and details of the study design and analysis, including the target parameter(s) and statistical methods used to analyse the ordinal outcome, will be extracted from eligible studies. The screening, review and data extraction will be conducted using Covidence, a web-based tool for managing systematic reviews. The data will be summarised using descriptive statistics.
Integrating pragmatic and implementation science randomized clinical trial approaches: a PRagmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) analysis
Authors: Zatzick Douglas , Palinkas Lawrence , Chambers David A. , Whiteside Lauren , Moloney Kathleen , Engstrom Allison , Prater Laura , Russo Joan , Wang Jin , Abu Khadija , Iles-Shih Matt , Bulger Eileen
Published: April 2023

Background

Over the past two decades, pragmatic and implementation science clinical trial research methods have advanced substantially. Pragmatic and implementation studies have natural areas of overlap, particularly relating to the goal of using clinical trial data to leverage health care system policy changes. Few investigations have addressed pragmatic and implementation science randomized trial methods development while also considering policy impact.

Methods

The investigation used the PRagmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) and PRECIS-2-Provider Strategies (PRECIS-2-PS) tools to evaluate the design of two multisite randomized clinical trials that targeted patient-level effectiveness outcomes, provider-level practice changes and health care system policy. Seven raters received PRECIS-2 training and applied the tools in the coding of the two trials. Descriptive statistics were produced for both trials, and PRECIS-2 wheel diagrams were constructed. Interrater agreement was assessed with the Intraclass Correlation (ICC) and Kappa statistics. The Rapid Assessment Procedure Informed Clinical Ethnography (RAPICE) qualitative approach was applied to understanding integrative themes derived from the PRECIS-2 ratings and an end-of-study policy summit.

Results

The ICCs for the composite ratings across the patient and provider-focused PRECIS-2 domains ranged from 0.77 to 0.87, and the Kappa values ranged from 0.25 to 0.37, reflecting overall fair-to-good interrater agreement for both trials. All four PRECIS-2 wheels were rated more pragmatic than explanatory, with composite mean and median scores ≥ 4. Across trials, the primary intent-to-treat analysis domain was consistently rated most pragmatic (mean = 5.0, SD = 0), while the follow-up/data collection domain was rated most explanatory (mean range = 3.14–3.43, SD range = 0.49–0.69). RAPICE field notes identified themes related to potential PRECIS-2 training improvements, as well as policy themes related to using trial data to inform US trauma care system practice change; the policy themes were not captured by the PRECIS-2 ratings.

Conclusions

The investigation documents that the PRECIS-2 and PRECIS-2-PS can be simultaneously used to feasibly and reliably characterize clinical trials with patient and provider-level targets. The integration of pragmatic and implementation science clinical trial research methods can be furthered by using common metrics such as the PRECIS-2 and PRECIS-2-PS. Future study could focus on clinical trial policy research methods development.

Trial registration

DO-SBIS ClinicalTrials.gov NCT00607620. registered on January 29, 2008. TSOS ClinicalTrials.gov NCT02655354, registered on July 27, 2015.
Butyrate driven raft disruption trots off enteric pathogen invasion: possible mechanism of colonization resistance
Authors: Das Oishika , Masid Aaheli , Chakraborty Mainak , Gope Animesh , Dutta Shanta , Bhaumik Moumita
Published: April 2023

The gut microbiome derived short chain fatty acids perform multitude of functions to maintain gut homeostasis. Here we studied how butyrate stymie enteric bacterial invasion in cell using a simplistic binary model. The surface of the mammalian cells is enriched with microdomains rich in cholesterol that are known as rafts and act as entry points for pathogens. We showed that sodium butyrate treated RAW264.7 cells displayed reduced membrane cholesterol and less cholera-toxin B binding coupled with increased membrane fluidity compared to untreated cells indicating that reduced membrane cholesterol caused disruption of lipid rafts. The implication of such cellular biophysical changes on the invasion of enteric pathogenic bacteria was assessed. Our study showed, in comparison to untreated cells, butyrate-treated cells significantly reduced the invasion of Shigella and Salmonella, and these effects were found to be reversed by liposomal cholesterol treatment, increasing the likelihood that the rafts' function against bacterial invasion. The credence of ex vivo studies found to be in concordance in butyrate fed mouse model as evident from the significant drift towards a protective phenotype against virulent enteric pathogen invasion as compared to untreated mice. To produce a cytokine balance towards anti-inflammation, butyrate-treated mice produced more of the gut tissue anti-inflammatory cytokine IL-10 and less of the pro-inflammatory cytokines TNF-α, IL-6, and IFN-γ. In histological studies of Shigella infected gut revealed a startling observation where number of neutrophils infiltration was noted which was correlated with the pathology and was essentially reversed by butyrate treatment. Our results ratchet up a new dimension of our understanding how butyrate imparts resistance to pathogen invasion in the gut.
Lipidomic landscape of circulating extracellular vesicles isolated from adolescents exposed to ethanol intoxication: a sex difference study
Authors: Perpiñá-Clérigues Carla , Mellado Susana , Català-Senent José F. , Ibáñez Francesc , Costa Pilar , Marcos Miguel , Guerri Consuelo , García-García Francisco , Pascual María
Published: April 2023

Background

Lipids represent essential components of extracellular vesicles (EVs), playing structural and regulatory functions during EV biogenesis, release, targeting, and cell uptake. Importantly, lipidic dysregulation has been linked to several disorders, including metabolic syndrome, inflammation, and neurological dysfunction. Our recent results demonstrated the involvement of plasma EV microRNAs as possible amplifiers and biomarkers of neuroinflammation and brain damage induced by ethanol intoxication during adolescence. Considering the possible role of plasma EV lipids as regulatory molecules and biomarkers, we evaluated how acute ethanol intoxication differentially affected the lipid composition of plasma EVs in male and female adolescents and explored the participation of the immune response.

Methods

Plasma EVs were extracted from humans and wild-type (WT) and Toll-like receptor 4 deficient (TLR4-KO) mice. Preprocessing and exploratory analyses were conducted after the extraction of EV lipids and data acquisition by mass spectrometry. Comparisons between ethanol-intoxicated and control human female and male individuals and ethanol-treated and untreated WT and TLR4-KO female and male mice were used to analyze the differential abundance of lipids. Annotation of lipids into their corresponding classes and a lipid set enrichment analysis were carried out to evaluate biological functions.

Results

We demonstrated, for the first time, that acute ethanol intoxication induced a higher enrichment of distinct plasma EV lipid species in human female adolescents than in males. We observed a higher content of the PA, LPC, unsaturated FA, and FAHFA lipid classes in females, whereas males showed enrichment in PI. These lipid classes participate in the formation, release, and uptake of EVs and the activation of the immune response. Moreover, we observed changes in EV lipid composition between ethanol-treated WT and TLR4-KO mice (e.g., enrichment of glycerophosphoinositols in ethanol-treated WT males), and the sex-based differences in lipid abundance are more notable in WT mice than in TLR4-KO mice. All data and results generated have been made openly available on a web-based platform (http://bioinfo.cipf.es/sal).

Conclusions

Our results suggest that binge ethanol drinking in human female adolescents leads to a higher content of plasma EV lipid species associated with EV biogenesis and the propagation of neuroinflammatory responses than in males. In addition, we discovered greater differences in lipid abundance between sexes in WT mice compared to TLR4-KO mice. Our findings also support the potential use of EV-enriched lipids as biomarkers of ethanol-induced neuroinflammation during adolescence.