bluuebunny/crossref_metadata_2025 huggingface dataset:
Is reduced heart rate variability associated with functional somatic disorders? A cross-sectional population-based study; DanFunD
Authors: Jørgensen Torben , Dantoft Thomas Meinertz , Petersen Marie Weinreich , Gormsen Lise , Winter-Jensen Matilde , Fink Per , Linneberg Allan , Benros Michael Eriksen , Eplov Lene Falgaard , Bjerregaard Anne Ahrendt , Schovsbo Signe Ulfbeck , Brinth Louise Schouborg
Published: February 2024

Objectives

It has been hypothesised that functional somatic disorders (FSD) could be initiated by sympathetic predominance in the autonomic nervous system as measured by low heart rate variability (HRV). Earlier studies on the association between HRV and FSD are small case–control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study is to assess any associations between HRV and various FSDs and whether chronic stress confounds such an association.

Design

A cross-sectional general population-based study.

Setting

The Danish Study of Functional Somatic Disorders conducted 2013–2015 in 10 municipalities in the western part of Greater Copenhagen, Denmark.

Participants

A total of 6891 men and women aged 18–72 years were included in the analyses after exclusion of 602 persons with missing HRV data. Various delimitations of FSD (chronic fatigue, chronic widespread pain, irritable bowel and bodily distress syndrome) were identified by validated questionnaires and diagnostic interviews. HRV parameters in time and frequency domains were calculated from successive beat-to-beat heart rate (HR) data using the ‘E-motion’ HR monitor device during 7 min of supine rest. Chronic stress was assessed by Cohen’s self-perceived stress scale.

Outcome measures

Logistic regression analyses were used to calculate possible associations between the various delimitations of FSD and HRV adjusting for chronic stress.

Results

Persons with FSD had a slightly higher mean HR and lower HRV as measured by time domain parameters, whereas associations with frequency domain parameters were not consistent. Adjusting for chronic stress attenuated associations slightly.

Conclusion

The study supports a sympathetic predominance in persons with FSD, which could not be entirely explained by chronic stress. However, it is not possible to conclude whether the association is a causal factor to or a consequence of FSD.
Efficacy of biological agents combined with oral immunotherapy (OIT) for food allergy: a protocol for a systematic review and meta-analysis
Authors: Honda Aiko , Okada Yoshiyuki , Matsushita Tomomi , Hasegawa Takeshi , Ota Erika , Noma Hisashi , Imai Takanori , Kwong Joey
Published: February 2024

Introduction

Food allergy affects a large population throughout the world. Recently, oral immunotherapy (OIT) has been reported as an effective treatment for severe food allergy. Although OIT was successful in numerous trials in desensitisation, adverse events including anaphylaxis during OIT frequently occur. Additionally, some patients fail to be desensitised after OIT and the response to treatment is often not sustained. As a further adjunctive therapy to facilitate OIT, the role of biological agents has been identified. For example, efficacy and safety of omalizumab as an adjuvant therapy of OIT has become apparent through some RCTs and observational studies. Interest towards this topic is growing worldwide, and ongoing trials will provide additional data on the biologics in food allergy.

We aim to systematically analyse the efficacy and safety of OIT combined with biological agents for food allergy.

Methods and analysis

This paper provides a protocol for a systematic review of the relevant published analytical studies using an aggregate approach following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Two authors will perform a comprehensive search for studies on MEDLINE/PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) databases. Subsequently, two independent authors will perform abstract screening, full-text screening and data extraction. A meta-analysis will be conducted as appropriate.

Ethics and dissemination

The protocol of this systematic review will be provided in a peer-reviewed journal. As the researchers will not identify the individual patients included in the studies, they do not need to acquire ethics approval.

PROSPERO registration number

CRD42022373015.
Study protocol for a prediction model for mild cognitive impairment in older adults with diabetes mellitus and construction of a nurse-led screening system: a prospective observational study
Authors: Miao Weiwei , Lu Yanling , Xv Honglian , Zheng Chen , Yang Wenwen , Qian Xiangyun , Chen Jianqun , Geng Guiling
Published: February 2024

Introduction

With an increasing number of older adults in China, the number of people with cognitive impairment is also increasing. To decrease the risk of dementia, it is necessary to timely detect mild cognitive impairment (MCI), which is the preliminary stage of dementia. The prevalence of MCI is relatively high among older adults with diabetes mellitus (DM); however, no effective screening strategy has been designed for this population. This study will construct a nurse-led screening system to detect MCI in community-dwelling older adults with DM in a timely manner.

Methods and analysis

A total of 642 participants with DM will be recruited (n=449 for development, n=193 for validation). The participants will be divided into MCI and none-MCI groups. The candidate predictors will include demographic variables, lifestyle factors, history of diseases, physical examinations, laboratory tests and neuropsychological tests. Univariate analysis, least absolute shrinkage and selection operator regression screening, and multivariate logistic regression analysis will be conducted to identify the outcome indicators. Based on the multivariate logistic regression equation, we will develop a traditional model as a comparison criterion for the machine learning models. The Hosmer-Lemeshow goodness-of-fit test and calibration curve will be used to evaluate the calibration. Sensitivity, specificity, area under the curves and clinical decision curve analysis will be performed for all models. We will report the sensitivity, specificity, area under the curve and decision curve analysis of the validation dataset. A prediction model with better performance will be adopted to form the nurse-led screening system.

Ethics and dissemination

This prospective study has received institutional approval of the Medical Ethics Committee of Qidong Hospital of TCM (QDSZYY-LL-20220621). Study results will be disseminated through conference presentations, Chinese Clinical Trial Registry and publication.

Trial registration number

ChiCTR2200062855.
Seroprevalence of Japanese encephalitis virus-specific antibodies in Australia following novel epidemic spread: protocol for a national cross-sectional study
Authors: Winkler Noni Ella , Koirala Archana , Kaur Guddu , Prasad Shayal , Hirani Rena , Baker Jannah , Hoad Veronica , Gosbell Iain B , Irving David O , Hueston Linda , O'Sullivan Matthew VN , Kok Jen , Dwyer Dominic E , Macartney Kristine
Published: February 2024

Introduction

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes encephalitis and other morbidity in Southeast Asia. Since February 2022, geographically dispersed JEV human, animal and vector detections occurred on the Australian mainland for the first time. This study will determine the prevalence of JEV-specific antibodies in human blood with a focus on populations at high risk of JEV exposure and determine risk factors associated with JEV seropositivity by location, age, occupation and other factors.

Method

Samples are collected using two approaches: from routine blood donors (4153 samples), and active collections targeting high-risk populations (convenience sampling). Consent-based sampling for the latter includes a participant questionnaire on demographic, vaccination and exposure data. Samples are tested for JEV-specific total antibody using a defined epitope-blocking ELISA, and total antibody to Australian endemic flaviviruses Murray Valley encephalitis and Kunjin viruses.

Analysis

Two analytic approaches will occur: descriptive estimates of seroprevalence and multivariable logistic regression using Bayesian hierarchical models. Descriptive analyses will include unadjusted analysis of raw data with exclusions for JEV-endemic country of birth, travel to JEV-endemic countries, prior JEV-vaccination, and sex-standardised and age-standardised analyses. Multivariable logistic regression will determine which risk factors are associated with JEV seropositivity likely due to recent transmission within Australia and the relative contribution of each factor when accounting for effects within the model.

Ethics

National Mutual Acceptance ethical approval was obtained from the Sydney Children’s Hospitals Network Human Research Ethics Committee (HREC). Local approvals were planned to be sought in each jurisdiction, as per local ethics processes. Ethical approval was also obtained from the Australian Red Cross Lifeblood HREC.

Dissemination

Findings will be communicated to participants and their communities, and human and animal health stakeholders and policy-makers iteratively and after final analyses. Understanding human infection rates will inform procurement and targeted allocation of limited JEV vaccine, and public health strategies and communication campaigns, to at-risk populations.
Developing interfaith interventions to address hesitancy towards COVID-19 vaccination: protocol for a focus group-based, exploratory qualitative study
Authors: Ali Farzana , Garfield Sara , Murdan Sudaxshina
Published: February 2024

Introduction

The COVID-19 pandemic demonstrated how vaccine hesitancy impacts are translated nationally and internationally. A predictor of vaccine hesitancy is religious beliefs (eg, the body being sacred and should be healed by God). Additionally, the perceived content of vaccines can conflict with religious dietary restrictions. Despite the main faith organisations in the UK endorsing COVID-19 vaccination, vaccine hesitancy remains a challenge. Most faith-based research and interventions have been investigated in individual faiths, in isolation from others. Therefore, the aim of our research is to inform the development of interfaith interventions to address COVID-19 vaccine hesitancy, following the identification of potential facilitators and barriers and codesign of interfaith intervention(s).

Methods and analysis

We will facilitate six face-to-face focus groups in London, each comprising eight participants. There will also be the option of joining an online focus group. A semistructured topic guide will include questions on experiences around interfaith, vaccine hesitancy, facilitators and barriers, and potential interfaith interventions to increase vaccine acceptance. Focus group participants will be invited to join a subsequent interfaith codesign workshop where the researchers will share the tentative findings and facilitate discussion to develop one or more interventions. Purposive sampling will be used to recruit 48 participants from different faith groups, ethnicities and backgrounds to capture diversity in the sample. Reflexive thematic analysis will guide a systematic process of constant comparison, coding data into categories and refining into overarching themes.

Ethics and dissemination

The University College London (UCL) Research Ethics Committee granted ethics approval (Project ID 4359.006) on 3 May 2022. Minor amendments to the study were approved on 15 May 2023 to accommodate participants’ requests for online or face-to-face focus groups at a UCL venue. Informed consent is required from all participants. The findings will be disseminated in journals and to the public and key stakeholders.
Research on the barriers to accessing sexual healthcare for sexually diverse Muslim men: protocol for a scoping review
Authors: Noor Muhammad Naveed , Shaw Souradet Y , Linton Janice , Lorway Robert
Published: February 2024

Introduction

Sexually diverse Muslim men are seen to be at a higher risk for HIV and other sexually transmitted infections due to their limited access to sexual healthcare services. We outline a protocol to conduct a scoping review of research on the barriers that may impede these men’s access to sexual healthcare.

Methods and analysis

To conduct this scoping review, we will follow the methodological framework developed by Arksey and O’Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses’ extension for scoping reviews. To classify the barriers to sexual healthcare, we will employ Bronfenbrenner’s socioecological model as a conceptual framework. We will conduct a literature search via Medline, Embase and Global Health (OVID); Scopus; CINAHL on EBSCOhost along with several other EBSCOhost databases (Academic Search Complete, Canadian Reference Centre, Alternative Press Index, Family & Society Studies Worldwide, Social Work Abstracts) and Google Scholar, published until November 2023. Journal articles, published in the English language, describing quantitative and qualitative research on sexual healthcare access barriers for sexually diverse Muslim men will be included in the review. Commentaries and correspondences, along with grey literature including research reports and conference abstracts, as well as studies that do not include men with the Muslim faith, will be considered ineligible. Following screening of titles and abstracts, we will conduct a full-text screening to determine the final number of studies to be included in the review. A Microsoft Excel spreadsheet will be used to extract study characteristics, and information on sexual healthcare access barriers will be classified according to the socioecological model’s core concepts.

Ethics and dissemination

Our review does not require ethics approval. We will disseminate the review findings through peer-reviewed academic journals, seminars and conference presentations.
Reporting and influencing factors of patient-reported outcomes in acupuncture randomised controlled trials: a cross-sectional study protocol
Authors: Duan Yuting , Zhao Pinge , Liu Shujuan , Deng Yuening , Xu Zhirui , Xiong Linghui , Chen Zewei , Zhu Weifeng , Wu Shengwei , Yu Lin
Published: February 2024

Introduction

Patient-reported outcomes (PROs) are health reports that come directly from the patients themselves and represented the experience and insights of the patient’s perspective on the impact of the intervention. PROs were increasingly emphasised in acupuncture randomised controlled trials (RCTs). However, the reporting quality of PROs in acupuncture RCTs has not been investigated to date. Therefore, we constructed this study to reveal the basic characteristics and reporting quality of PROs in acupuncture RCTs, and explore the relationship between concealment, blinding and RROs. We hope our findings can provide guidance for the reporting standards and future development of PROs in acupuncture RCTs in reverse.

Methods and analysis

RCTs using acupuncture treatment as the intervention and PROs as primary outcomes or secondary outcomes will be systematically searched through seven databases MEDLINE, EMBASE, CENTRAL, CBM, CNKI, Wanfang and VIP between 1 January 2012 and 15 October 2022. The basic characteristics, concealment, blinding design and the characteristics of PROs in included RCTs will be summarised. The reporting quality of PROs will be assessed based on the CONSORT PRO extension. Logistic analysis will be performed to identify the association between concealment, blinding and RROs.

Ethics and dissemination

Ethical approval is not required for this study. This protocol has been registered in Open Science Framework (OSF) Registries. The findings of this study will be submitted to a peer-reviewed academic journal.
Understanding the use and outcomes of high-flow nasal cannula among infants admitted to Canadian hospitals with bronchiolitis (CanFLO): a protocol for a multicentre, retrospective cohort study
Authors: D’Alessandro Michelle , Fricano Chiara , Abdulsatar Farah , Bechard Nicole , Brar Jagraj Singh , Drouin Olivier , Foulds Jessica L , Giglia Lucia , Gill Peter J , Gupta Ronish , Li Patricia , McConnery Jason , Metcalf Jason , Sakran Mahmoud , Seaton Claire , Sehgal Anupam , Sirizzotti Natalie , Mbuagbaw Lawrence , Wahi Gita
Published: February 2024

Introduction

Bronchiolitis is the most common viral lower respiratory tract infection in children under 2 years of age. Respiratory support with high-flow nasal cannula (HFNC) is increasingly used in this patient population with limited understanding of the patients most likely to benefit and considerable practice variability of use. This study aims to understand the factors associated with failure of HFNC support among patients with bronchiolitis and to describe the current practice variations of HFNC use in patients with bronchiolitis in Canadian hospitals including fluid management and parameters to initiate, escalate and discontinue HFNC support.

Methods and analysis

This is a multicentre retrospective cohort study including hospitalised patients aged 0–24 months with bronchiolitis requiring support with HFNC between January 2017 and December 2021. Clinical data will be collected from patient medical records from Canadian hospitals (n=12), including academic and community centres. HFNC failure will be defined as the need for escalation to non-invasive or invasive mechanical ventilation. Factors associated with HFNC failure will be analysed using logistic regression. Descriptive statistics will be used to describe practice variations of HFNC utilisation and management.

Ethics and dissemination

Approval from the Research Ethics Boards (REBs) has been obtained for each participating study site prior to onset of data collection including Clinical Trials Ontario for all Ontario hospital sites and REBs from British Columbia Children’s Hospital, Stollery Children’s Hospital, Montreal Children’s Hospital and CHU Sainte-Justine. Study results will be disseminated through presentation at national/international conferences and publication in high-impact, peer-reviewed journals.
Strategies for treating acute pain in patients with opioid dependence: a scoping review protocol
Authors: Levine Sarah , Andrews Megha , Saracco Benjamin , Salzman Matthew
Published: February 2024

Introduction

People who are dependent on opioids experience acute pain similar to other individuals. However, treating acute pain in these patients renders unique challenges such as opioid-induced hyperalgesia, opioid tolerance, withdrawal and stigma from healthcare providers. Thus, it is crucial to identify effective strategies for treating acute pain in this population and to highlight gaps in knowledge to create a high standard of care. The main objective of the proposed scoping review is to identify current strategies for treating the acute pain in individuals with opioid dependence or use disorder.

Methods and analysis

MEDLINE via the PubMed interface, Embase and Cochrane Central, Web of Science: Conference Proceedings Citation Index and Google Scholar will be searched. Forward and backward citation searching of the final included studies will also be conducted. Two independent reviewers will screen the titles and abstracts of sources, review and assess relevant full-text studies and extract data. Data will be presented in a diagram and will contribute to a qualitative thematic analysis.

Ethics and dissemination

Data will be gathered from publicly accessible sources, so ethics approval is not necessary. The results will be disseminated through a peer-reviewed journal and reported at conferences related to addiction medicine.

Trial registration number

10.17605/OSF.IO/BG6SJ.
Improving handoff with the implementation of I-PASS at a tertiary oncology hospital
Authors: Franco Vega Maria C , Ait Aiss Mohamed , Smith Maura , George Marina , Day Lakeisha , Mbadugha Anayo , Niangar Zalie , Bodurka Diane
Published: February 2024

Background

Lack of consistent and standardised handoffs is a leading cause of patient harm. With increased census in our hospital medicine (HM) service, failure to handoff using a standardised method has the potential to cause significant patient harm. We used a quality improvement methodology to standardise an existing and validated handoff tool within our HM team to improve handoff communication among providers and improve patient safety.

Methods

A quality improvement team was charged with studying handoff communication among HM teams and between day and night shift providers at a tertiary oncology hospital. Multiple plan-do-study-act cycles were conducted, and process flow maps, root cause analysis and an affinity diagram were developed based on feedback from the HM team. The quality improvement team developed a plan to implement I-PASS (Illness severity, Patient summary, Action list, Situation awareness and contingency plan, and Synthesis by receiver) as the standardised handoff tool to be used among the providers in HM at the end of shift and for handoff to the nocturnal covering service. Rates of I-PASS use were collected before and after several educational interventions to encourage use of I-PASS and were displayed in a control chart. After the I-PASS interventions, HM providers were surveyed twice to evaluate the secondary outcomes: the tool’s impact on workflow, perceptions of patient safety, ease of use and satisfaction with I-PASS. Survey results were compared using Fisher exact tests.

Results

The HM team’s rate of use of I-PASS handoffs increased from 23% to 72%, an improvement of 68%. By the end of the quality improvement project, I-PASS use had increased to 90%. No significant differences were detected in the reported duration of handoffs after I-PASS implementation (on average <5 min per patient, p=0.205). Provider perceptions of handoff quality, efficiency, communication errors and the I-PASS tool’s effectiveness were satisfactory.

Conclusion

We used a quality improvement methodology to encourage the HM team’s adoption of a validated handoff tool. Adherence to the standardised handoff tool significantly improved workflows and facilitated communication between the day and night shift teams.
Injury incidence in male elite youth football players is associated with preceding levels and changes in training load
Authors: Nilsson Tania , Börjesson Mats , Lundblad Matilda , Ivarsson Andreas , Fransson Dan
Published: February 2024

Objectives

Elite youth football players miss out on a large part of seasonal training due to injury. Limited research suggests an association between external and internal training load (TL) and injury incidence in elite youth football. This study analysed external and internal TL variables and their association with injury incidence in a group of male elite youth football players over four seasons.

Methods

Measures of external and internal TL and injury incidence of 56 male elite youth football players (age 17–19 years) were collected throughout four seasons. Heart rate, session rating of perceived exertion andGlobal Positioning System (GPS) variables were analysed. Individual players’ TL during the 30 days leading up to injury was compared with 30-day injury-free control periods. Change in TL through the periods was also analysed.

Results

Eighty-five injuries were included for analysis, showing that for most TL variables, the average levels were significantly lower during the period leading up to injury. Significant increases for the majority of TL variables were also found during the periods leading up to injury, while the control periods did not show any significant change.

Conclusion

A lower and/or increasing average TL volume over 30 days might increase the risk of injury in male elite youth football players. Avoiding long-term drops in TL and balance increases in TL might be beneficial to reduce injury risk.
A musculoskeletal multifactorial individualised programme for hamstring muscle injury risk reduction in professional football: results of a prospective cohort study
Authors: Edouard Pascal , Lahti Johan , Fleres Luca , Ahtiainen Juha , Ulvila Juha-Jaakko , Lehtinen Tiitus , Virtanen Niklas , Taipale Toni , Bellver Michel , Peltonen Ville , Thibault Max , Huuhka Toni , Toivonen Risto-Matti , Morin Jean-Benoit , Mendiguchia Jurdan
Published: February 2024

Objective

To test whether a musculoskeletal multifactorial and individualised hamstring muscle injury (HMI) risk reduction programme could reduce HMI risk in professional football.

Methods

We conducted a prospective cohort study in Finnish premier football league teams, with the 2019 season used as a control and an intervention conducted in the 2021 season. Screening was conducted to provide individualised programmes and monitor progress. Cox regression with hazard ratio (HR) was used with HMI as outcome and season as explanatory variable, including all players for primary analysis and those who performed the two seasons for secondary analysis.

Results

90 players were included in the control and 87 in the intervention seasons; 31 players performed in the 2 seasons. Twenty HMIs were recorded during the control and 16 during the intervention seasons. Cox regression analyses revealed that HMI risk at any given time was not significantly different between control and intervention seasons (for all players: HR 0.77 (95% CI 0.39 to 1.51), p=0.444; for the 31 players: HR 0.32 (95% CI 0.01 to 1.29), p=0.110)). For the 31 players, the HMI burden was significantly reduced in the intervention compared with the control season (RR 0.67 (95% CI 0.53 to 0.85)). Higher compliance with knee strength training, maximal velocity exposure and lower performance reductions in maximal theoretical horizontal force and knee flexor force were associated with lower HMI incidence.

Conclusions

Although the primary analysis did not reveal any significant effect of the intervention to reduce HMI risk in professional football, the programme was feasible, and additional secondary analyses showed a significant association between the intervention and lower HMI burden, incidence and risk.
Living with myocardial ischaemia and no obstructive coronary arteries: a qualitative study
Authors: Humphreys Helen , Paddock Danielle , Brown Sarah , Berry Colin , Cowie Aynsley , Dawkes Susan , Nichols Simon
Published: February 2024

Objective

To explore the lived experience of people with myocardial ischaemia with no obstructive arteries.

Design

Qualitative study using semistructured interviews.

Setting

Telephone interviews with 17 participants living in the UK.

Participants

17 people (2 males, 15 females; aged 31–69 years) with a presumed or confirmed diagnosis of myocardial ischaemia with no obstructive arteries, recruited via social media and online patient-led support forums.

Results

Five themes were generated. Theme 1 describes the wide range of experiences that participants described, particularly the frequency and intensity of symptoms, and the uncertainty and fear that symptoms commonly provoked. Theme 2 describes the major impact on social relationships, employment and other aspects of everyday life. Theme 3 illustrates challenging and traumatising experiences participants described around pathways to diagnosis and accessing medical support. Theme 4 highlights the lack of consensus and clarity that participants had been confronted with around treatment and management. Theme 5 describes coping and supportive strategies valued by participants.

Conclusions

This study provides insight into the challenges of living with myocardial ischaemia with no obstructive arteries. Findings highlight the significant psychological impact on people living with these conditions and the need for improvements in diagnosis, support and long-term management.
PM10increases mortality risk in rheumatoid arthritis-associated interstitial lung disease
Authors: Kim Soo Han , Kim Sun-Young , Yoon Hee-Young , Song Jin Woo
Published: February 2024

Objectives

The effect of air pollution on the prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) remains poorly understood. We aimed to evaluate the effect of long-term exposure to particulate matter with an aerodynamic diameter of ≤10 µm (PM10) and nitrogen dioxide (NO2) on mortality in patients with RA-ILD.

Methods

We included 309 patients (mean age, 61.7 years; male, 44.3%) with RA-ILD. Individual-level long-term exposures to PM10and NO2at their residential addresses were estimated using a national-scale exposure prediction model. The effect of the two air pollutants on mortality was estimated using a Cox-proportional hazards model adjusted for individual-level and area-level characteristics.

Results

The median follow-up period was 4.8 years, and 40.8% of patients died or underwent lung transplantation. The annual average concentrations of PM10and NO2were 56.3 μg/m3and 22.4 ppb, respectively. When air pollutant levels were stratified by quartiles, no association was observed between air pollutant concentration and mortality in patients with RA-ILD. However, when stratified by two groups (high exposure (top 25th percentile) vs low exposure (bottom 75th percentile)), we observed a significant association between high PM10exposure and mortality (HR 1.68; 95% CI 1.11 to 2.52; p=0.013) but no association between NO2exposure and mortality. In the subgroup analyses, the effect of high PM10exposure on mortality was significant in patients aged <65 years (HR 1.98; 95% CI 1.02 to 3.85; p=0.045).

Conclusions

Our results indicated that high PM10exposure may be associated with mortality in patients with RA-ILD.
Reappraisal of large artery involvement in giant cell arteritis: a population-based cohort over 70 years
Authors: Elfishawi Mohanad M , Kaymakci Mahmut S , J Achenbach Sara , S Crowson Cynthia , Kermani Tanaz A , M Weyand Cornelia , J Koster Matthew , Warrington Kenneth J
Published: February 2024

Objective

To evaluate the incidence and outcomes of large artery (LA) involvement among patients with giant cell arteritis (GCA) and to compare LA involvement to non-GCA patients.

Methods

The study included Olmsted County, Minnesota, USA residents with incident GCA between 1950 and 2016 with follow-up through 31 December 2020, death or migration. A population-based age-matched/sex-matched comparator cohort without GCA was assembled. LA involvement included aortic aneurysm, dissection, stenosis in the aorta or its main branches diagnosed within 1 year prior to GCA or anytime afterwards. Cumulative incidence of LA involvement was estimated; Cox models were used.

Results

The GCA cohort included 289 patients (77% females, 81% temporal artery biopsy positive), 106 with LA involvement.

Reported cumulative incidences of LA involvement in GCA at 15 years were 14.8%, 30.2% and 49.2% for 1950–1974, 1975–1999 and 2000–2016, respectively (HR 3.48, 95% CI 1.67 to 7.27 for 2000–2016 vs 1950–1974).

GCA patients had higher risk for LA involvement compared with non-GCA (HR 3.22, 95% CI 1.83 to 5.68 adjusted for age, sex, comorbidities). Thoracic aortic aneurysms were increased in GCA versus non GCA (HR 13.46, 95% CI 1.78 to 101.98) but not abdominal (HR 1.08, 95% CI 0.33 to 3.55).

All-cause mortality in GCA patients improved over time (HR 0.62, 95% CI 0.41 to 0.93 in 2000–2016 vs 1950–1974) but remained significantly elevated in those with LA involvement (HR 1.89, 95% CI 1.39 to 2.56).

Conclusions

LA involvement in GCA has increased over time. Patients with GCA have higher incidences of LA involvement compared with non-GCA including thoracic but not abdominal aneurysms. Mortality is increased in patients with GCA and LA involvement highlighting the need for continued surveillance.
Prognostic factors for survival in unresectable stage III EGFR mutation-positive lung adenocarcinoma: impact of pre-CCRT PET-CT
Authors: Lin Wei-Chun , Chen Wan-Ming , Shia Ben-Chang , Wu Szu-Yuan
Published: February 2024

Purpose

To assess the survival impact of pre-concurrent chemoradiotherapy (CCRT) staging with positron emission tomography-CT (PET-CT) in patients with unresectable epidermal growth factor receptor (EGFR) mutation-positive adenocarcinoma.

Methods

Patients with unresectable stage IIIA–IIIC EGFR mutation-positive adenocarcinoma undergoing definitive CCRT were divided into two groups: those who received PET-CT staging prior to CCRT and those with other staging methods. Survival outcomes were compared after propensity score matching.

Results

Analysis of 11 856 patients (5928 in each group) showed that PET-CT staging was associated with improved survival (adjusted HR of all-cause mortality: 0.74, 95% CI 0.71 to 0.79). Other prognostic factors included male sex, age group, clinical stage, adjuvant treatment, smoking status, Charlson Comorbidity Index score and treatment setting.

Conclusion

Pre-CCRT staging with PET-CT in patients with unresectable EGFR mutation-positive adenocarcinoma of clinical stage IIIA–IIIC was associated with enhanced survival. Independent prognostic factors were also identified.
Results validation by using finite volume method for the blood flow with magnetohydrodynamics and hybrid nanofluids
Authors: Haider Jamil Abbas , Ahmad Shahbaz , Ghazwani Hassan Ali , Hussien Mohamed , Almusawa Musawa Yahya , Az-Zo’bi Emad A.
Published: February 2024

This paper conducts an extensive comparative analysis of numerical methods employed in modeling blood flow through arteries with Magnetohydrodynamics (MHD) and hybrid nanofluids. The study investigates the effectiveness and precision of distinct numerical approaches: Akbari Ganji’s Method (AGM), Fourth-Order Runge–Kutta (RK4), Finite Volume Method (FVM), and the Finite Element Method (FEM). These methods are essential for comprehending the intricate fluid dynamics that arise in the presence of magnetic fields and hybrid nanofluids a phenomenon relevant in numerous medical applications. Blood flow is subjected to a homogeneous magnetic field in a radial direction while the magneto-hemodynamics effect is taken into account. A variety of medical, physiological, and surgical procedures, as well as the regulation of blood pressure, heat distribution, wound healing, diagnostic imaging, and drug discovery, depend on blood flow through arteries to carry out vital functions such as oxygen and nutrition delivery, organ maintenance, and wound healing. Our findings highlight that while each method has strengths, their applicability varies based on the problem’s characteristics and computational resource constraints. This analysis aids researchers and practitioners in selecting the most suitable method for their modeling requirements, advancing numerical techniques for complex fluid dynamics involving MHD and hybrid nanofluids.
Investigating the Impact of Catalyst Penetration into Gas Diffusion Layer on the Performance of High-Temperature Polymer Electrolyte Membrane Fuel Cells
Authors: Chippar Purushothama , K P Venkatesh Babu
Published: February 2024

The catalyst fabrication method, cell assembly, and operating conditions in polymer electrolyte membrane fuel cells (PEMFC) impact the catalyst penetration into the gas diffusion layer (GDL), alter its porous structure, and, consequently, the overall cell performance. This study investigates the effect of the catalyst layer (CL) penetration thickness, catalyst loading amount, and cell compression during assembly on species and current distributions, and overall cell performance. GDLs with large penetration thickness show a substantial resistance to reactant and proton transport, particularly at high current densities resulting in a drop in the cell performance. For zero, 50%, and 100% penetrations, the average current densities at an operating voltage of 0.4 V are 0.8329, 0.7920, and 0.71112 A cm−2, respectively. This indicates a performance loss of 5% and 15% for 50% and 100% penetrations in comparison to zero penetration. Higher catalyst loading results in greater penetration, negating the benefit of enhanced kinetics. Performance typically decreases by 3%–5% for 50% penetration and 12%–15% for 100% penetration when penetration levels increase for a certain Pt loading. An attempt is made to investigate the interplay between the effect of reactant and proton transport limitations on their distributions and cell performance. The combined effect of catalyst penetration and cell compression during the assembly has a crucial impact on cell performance with the starvation of reactants at high-density regions. The study highlights the necessity of optimizing the penetration thickness, catalyst loading, and cell assembly to achieve maximum cell performance.
Plasminogen deficiency exacerbates skeletal muscle loss during mechanical unloading in developing mice
Authors: Ohira Takashi , Ino Yoko , Kawao Naoyuki , Mizukami Yuya , Okada Kiyotaka , Matsuo Osamu , Hirano Hisashi , Kimura Yayoi , Kaji Hiroshi
Published: February 2024

The expression levels of fibrinolysis-related proteins, including plasminogen, were significantly elevated in the gastrocnemius (Gast) and soleus muscles of mice following 30-day microgravity exposure. Plasminogen deficiency exacerbated atrophy of the Gast, but not the soleus, muscles in mice following 21-day hindlimb suspension. It was also suggested that protein breakdown via the autophagy-lysosome system was accelerated in the Gast muscles. Plasminogen might play some protective roles against muscle atrophy induced by mechanical unloading in developing mice.
Effect of exercise modalities on postexercise hypotension in pre- and postmenopausal women: a systematic review and meta-analysis
Authors: Le Bourvellec Morgane , Delpech Nathalie , Hervo Jéromine , Bosquet Laurent , Enea Carina
Published: February 2024

This meta-analysis has demonstrated that a single bout of exercise induces postexercise hypotension (PEH) in women and that the hormonal shift occurring with menopause does not influence the magnitude of PEH. However, we have shown with moderate evidence that the effectiveness of exercise modalities differs between pre- and postmenopausal women. Resistance and combined exercises are the best modalities to induce PEH in premenopausal women, whereas resistance and aerobic exercises are more effective in postmenopausal women.
Navigating the multifaceted intricacies of the Na+-Cl− cotransporter, a highly regulated key effector in the control of hydromineral homeostasis
Authors: Rioux A. V. , Nsimba-Batomene T. R. , Slimani S. , Bergeron N. A. D. , Gravel M. A. M. , Schreiber S. V. , Fiola M. J. , Haydock L. , Garneau A. P. , Isenring P.
Published: February 2024

The Na+-Cl− cotransporter (NCC; SLC12A3) is a highly regulated integral membrane protein that is known to exist as three splice variants in primates. Its primary role in the kidney is to mediate the cosymport of Na+ and Cl− across the apical membrane of the distal convoluted tubule. Through this role and the involvement of other ion transport systems, NCC allows the systemic circulation to reclaim a fraction of the ultrafiltered Na+, K+, Cl−, and Mg+ loads in exchange for Ca2+ and [Formula: see text]. The physiological relevance of the Na+-Cl− cotransport mechanism in humans is illustrated by several abnormalities that result from NCC inactivation through the administration of thiazides or in the setting of hereditary disorders. The purpose of the present review is to discuss the molecular mechanisms and overall roles of Na+-Cl− cotransport as the main topics of interest. On reading the narrative proposed, one will realize that the knowledge gained in regard to these themes will continue to progress unrelentingly no matter how refined it has now become.
Significantly Delayed Development of Polyarthritis with Active Tenosynovitis after Possible Temporary Neutropenic Immune-Related Adverse Events Caused by Atezolizumab Treatment: A Novel Case Report
Authors: Saito Yoshitaka , Takekuma Yoh , Asahina Hajime , Hisada Ryo , Sugawara Mitsuru
Published: February 2024

Immune checkpoint inhibitors have drastically improved cancer treatment. However, they may induce immune-related adverse events (irAEs). Here, we report a case of significantly delayed rheumatic irAEs (Rh-irAEs) with prior possible temporary neutropenic irAEs in a patient with atezolizumab-treated non-small-cell lung cancer and its management. A man in his sixties received atezolizumab monotherapy as the sixth-line treatment. He experienced an infusion-related reaction (fever) during the first cycle. On day 22 of cycle 2, grade 4 neutropenia suddenly appeared, but it disappeared on the next day. Cycle 3 was initiated after seven days; the patient did not exhibit any symptoms for approximately 500 days. However, on day 534 (day 1 of cycle 21), the patient complained of pain in the shoulders, back, and wrists. On day 644, the shoulder and back pain worsened with obvious swelling of the fingers. We thus suspended treatment and consulted a rheumatologist. A diagnosis of polyarthritis with active tenosynovitis was made based on joint ultrasound and laboratory tests. Prednisolone 15 mg attenuated the symptoms, allowing suspension of analgesics; however, dose reduction from 15 mg/day was difficult because of symptom flares. Finally, iguratimod 25 mg twice daily was initiated on day 764; prednisolone was reduced to 10 mg without flares, and its dosage was slowly reduced to 5 mg/day. Although irAEs exhibit multisystem features, delayed development of polyarthritis with active tenosynovitis after possible temporary neutropenic irAEs is rare. Thus, irAEs need to be monitored for a long time in patients with suspected irAE development even if it appears transiently.
In Silico Investigation of Novel Compounds as Inhibitors of Acetylcholinesterase Enzyme for the Treatment of Alzheimer’s Diseases
Authors: Adebambo Kassim , Ojoh Oghenekevwe (Claudia)
Published: February 2024

Alzheimer’s disease (AD) is a “progressive, neurodegenerative disease that occurs when nerve cells in the brain die.” There are only 4 drugs approved by the United States Food and Drug Administration (FDA). Three (donepezil, rivastigmine, and galantamine) out of these four drugs are anticholinesterase inhibitors, while the fourth one memantine is an N-methyl-D-aspartate (NMDA) receptor inhibitor. Currently, two immunotherapy drugs that target amyloid protein (donanemab and lecanemab) are being considered for the treatment of Alzheimer’s disease at an early stage. All these drug molecules are still not the complete answer to the treatment of Alzheimer’s disease. A recent report from the Office of National Statistics showed that AD is the leading cause of death in 2022. Therefore, there is an urgency to develop more drugs that can treat AD. Based on this urgency, we aim to investigate how bioactive and already approved drugs could be repurposed for inhibiting the anticholinesterase enzyme using computational studies. To achieve this, the data science tool—Python coding was compiled on Jupyter Notebook to mine bioactive compounds from the ChEMBL database. The most bioactive compounds obtained were further investigated using Molecular Operating Environment (MOE) software to carry out molecular docking and ligand analysis, and this was followed by molecular dynamics simulation production at 35 ns using GROMACS 2022.4 on Archer 2 machine. The molecular dynamic analysis was carried out using HeroMDanalysis software. Data mining of the ChEMBL database was carried out for lipase inhibitors, and this gave CHEMBL-ID 1240685, a peptide molecule, the most active compound at the time of data mining. Further literature studies gave Zoladex an FDA-approved drug for the treatment of breast cancer as another compound of interest. The in silico studies were carried out against the anticholinesterase enzyme using two FDA-approved drugs donepezil and galantamine as a template for comparing the in silico activities of the repurposed drugs. A very useful receptor for this study was PDB-1DX6, a cocrystallized galantamine inhibitor of acetylcholinesterase enzyme. The molecular docking analysis (using ligand interactions) and molecular dynamic analysis (root mean square deviation (RMSD) and root mean square fluctuation (RMSF)) showed that the two peptide molecules CHEMBL-1240685 and Zoladex gave the best binding energy and stability when compared to the FDA-approved drugs (donepezil and galantamine). Finally, further literature studies revealed that Zoladex affects memory reduction; therefore, it was dropped as a possible repurposed drug. Our research showed that CHEMBL-1240685 is a potential compound that could be investigated for the inhibition of anticholinesterase enzyme and might be another drug molecule that could be used to treat Alzheimer’s disease.
Qingfei Tongluo Mixture Attenuates Bleomycin-Induced Pulmonary Inflammation and Fibrosis through mTOR-Dependent Autophagy in Rats
Authors: Ge Shuyu , Guo Zhenghong , Xiao Ting , Sun Pingping , Yang Bo , Ying Yin
Published: February 2024

As an interstitial fibrosis disease characterized by diffuse alveolitis and structural alveolar disorders, idiopathic pulmonary fibrosis (IPF) has high lethality but lacks limited therapeutic drugs. A hospital preparation used for the treatment of viral pneumonia, Qingfei Tongluo mixture (QFTL), is rumored to have protective effects against inflammatory and respiratory disease. This study aims to confirm whether it has a therapeutic effect on bleomycin-induced IPF in rats and to elucidate its mechanism of action. Male SD rats were randomly divided into the following groups: control, model, CQ + QFTL (84 mg/kg chloroquine (CQ) + 3.64 g/kg QFTL), QFTL-L, M, H (3.64, 7.28, and 14.56 g/kg, respectively) and pirfenidone (PFD 420 mg/kg). After induction modeling and drug intervention, blood samples and lung tissue were collected for further detection. Body weight and lung coefficient were examined, combined with hematoxylin and eosin (H&E) and Masson staining to observe lung tissue lesions. The enzyme-linked immunosorbent assay (ELISA) and the hydroxyproline (HYP) assay kit were used to detect changes in proinflammatory factors (transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β)) and HYP. Immunohistochemistry and Western blotting were performed to observe changes in proteins related to pulmonary fibrosis (α-smooth muscle actin (α-SMA) and matrix metalloproteinase 12 (MMP12)) and autophagy (P62 and mechanistic target of rapamycin (mTOR)). Treatment with QFTL significantly improved the adverse effects of bleomycin on body weight, lung coefficient, and pathological changes. Then, QFTL reduced bleomycin-induced increases in proinflammatory mediators and HYP. The expression changes of pulmonary fibrosis and autophagy marker proteins are attenuated by QFTL. Furthermore, the autophagy inhibitor CQ significantly reversed the downward trend in HYP levels and α-SMA protein expression, which QFTL improved in BLM-induced pulmonary fibrosis rats. In conclusion, QFTL could effectively attenuate bleomycin-induced inflammation and pulmonary fibrosis through mTOR-dependent autophagy in rats. Therefore, QFTL has the potential to be an alternative treatment for IPF in clinical practice.