bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential role for human menopausal gonadotropin in ovine superovulatory regimens during the breeding season
Authors: Zhang Jing , Lu Xiaoyu , Liu Yiyong , Wu Xinglong , Yu Yuansong , Li Xiangyun
Published: March 2023

Human menopausal gonadotrophin (hMG) has been reported to produce a comparable superovulatory response to that of follicle stimulating hormone (FSH). Furthermore, hMG has a long half‐life as compared with FSH. The present study was designed to compare hMG administered once daily and FSH administered twice daily over a 4 ‐ day period on superovulatory response of Suffolk ewes. During the mid‐luteal phase, twenty‐four Suffolk donor ewes received intravaginal sponges at day 0 for 12 days. The superovulatory regimens in the Control group (n = 12) and the Treatment group (n = 12) consisted of eight injections of FSH given at twice daily and four injections of hMG given at once daily, respectively. At day 13, the donor ewes were subjected to laparoscopic insemination. Embryos were recovered, classified, and transferred to recipient ewes at day 19. Pregnancy status was determined by ultrasound examination 40 days after transfer. Lambing rate was calculated after all the ewes had delivered. No significant differences were observed between the two groups in terms of the structures recovered, transferable embryos, degenerated embryos, unfertilized oocytes, pregnancy rate and lambing rate. The results showed that once daily injection of hMG can produce a comparable superovulatory response and embryo transfer outcomes to those obtained by twice daily injection of FSH over a 4 ‐ day period. It is feasible that hMG is used to replace FSH and reduce the number of injection treatments in ovine superovulatory regimens.
Reconstructing Gender Roles using Collective Memory (Process) through Select Indian Commercials
Authors: M S Glint John , G Bhuvaneswari
Published: March 2023

Collective memory as a process implies that social groups' collective memory in society, changes and develops over time. The paper adopts a phenomenological study using Yadin Dudai’s ‘collective memory as a process’, in the interest of assessing how shifting collective memory (process) of gender roles in society influences the depiction of gender roles in Indian television commercials. Further, it goes on to explain how such advertisements can also impact society's collective memory of gender roles. The study investigates the issue of whether or not there has been a shift in how gender roles are portrayed in commercials in association with the collective memory (process) of society. Studying this change in the portrayal of gender roles in television advertising does indeed have broader implications as to how society perceives gender roles, emphasizing the significance of this study. The research findings show that there has been a noticeable change in how women are portrayed in television commercials as sporting champions, motorists, successful politicians, and business personnel in relation to the changing collective memory of society. The study ultimately determines that the influence of commercials on modifying society's collective memory of gender roles and the influence of collective memory on the evolution of gender role depictions in commercials are reciprocal in nature.
The Effect of Remote Myofascial Release on Chronic Nonspecific Low Back Pain With Hamstrings Tightness
Authors: Tamartash Hassan , Bahrpeyma Farid , Dizaji Manijhe Mokhtari
Published: March 2023

Context: Anatomy trains theory states that performing techniques in any part of the superficial myofascial backline can remotely treat other parts of this pathway. Due to the connections of different parts of the superficial backline, it is possible to influence the hamstring by performing the technique in the lumbar area. As chronic nonspecific low back pain (LBP) may lead to or be caused by hamstring tightness, remote myofascial release (MFR) techniques using the superficial backline can help improve hamstring tightness. Objective: This study aimed to evaluate the effect of remote MFR on hamstring tightness for those with chronic nonspecific LBP. Design: Single-blind, parallel design. Setting: The present study was performed at the clinical setting of Tarbiat Modares University in Iran. Methods: This study included 40 participants (20 males and 20 females) who were 40.5 (5.3) years old with chronic nonspecific LBP and hamstring tightness. Interventions: Participants were randomly divided into the lumbar MFR (remote area) and hamstring MFR groups. Participants underwent 4 sessions of MFR for 2 weeks. Main Outcome Measures: A passive knee-extension (PKE) test was used for muscle tightness evaluation 3 times. Results: Repeated-measure analysis of variance test showed that after the lumbar and hamstring MFR, the PKE was significantly reduced in both legs: lumbar MFR (right knee: from 61.04° [2.17°] to 51.01° [4.11°], P ≤ .003 and left knee: from 63.02° [3.12°] to 52.09° [2.48°], P ≤ .004) and hamstring MFR (right knee: from 62.01° [4.32°] to 50.50° [7.18°], P ≤ .001 and left knee: from 63.11° [2.56°] to 51.32° [5.31°], P ≤ .002). Least Significant Difference (LSD) post hoc test results showed that the 2 groups were not significantly different after the MFR (P ≥ .05). Also, the intraclass correlation coefficient index showed that the PKE test has excellent reliability (intraclass correlation coefficient, .910 for the right limb and .915 for the left limb). The minimal detectable change at the 95% confidence interval indicated that a change greater than or equal to 6° is required to exceed the threshold of the error PKE test, respectively. Conclusion: The present study showed that the remote MFR technique to the lumbar region demonstrated the same significant results in decreasing hamstring tightness as was noted in hamstring MFR to both limbs in patients with chronic nonspecific LBP.
Achieving cognitive liberty
The Battle for Your Brain: Defending the Right to Think Freely in the Age of Neurotechnology
Nita A. Farahany
St. Martin’s Press, 2023. 288 pp.
Authors: Muñoz José M.
Published: March 2023

Neurotechnologies necessitate new thinking on human rights
A massive machine regulates cell death
Authors: Mace Peter D. , Day Catherine L.
Published: March 2023

Structural analysis reveals how the decision to induce apoptotic cell death is regulated
Paul Berg (1926–2023)
Authors: Baltimore David
Published: March 2023

Father of genetic engineering
Let’s change what’s possible
Authors: Prabhakar Arati
Published: March 2023

America’s science, technology, and innovation ecosystem is a powerful engine for progress, but it was conceived in the last century for last century’s goals. Today, the nation’s aspirations have never been bigger: robust health and ample opportunity for everyone, tackling the climate crisis and using it to reimagine infrastructure and humanity’s relationship with nature, global security and stability, a competitive economy that creates good-paying jobs, and a strong, thriving democracy. The purpose of science and technology is to open the doors that make these aspirations possible. As President Biden said, “We can channel the full talents of all our people into a greater measure of hope and opportunity for our nation and for the world.”
Do COVID-19 vaccine mandates still make sense?
Authors: Vogel Gretchen
Published: March 2023

Ineffective or outdated requirements could undermine trust, some vaccine researchers say
Active volcano shows Venus is a living planet
Authors: Voosen Paul
Published: March 2023

Eruption spotted in 30-year-old data from Magellan mission
Schizophrenia pinpointed as a key factor in heat deaths
Authors: Cornwall Warren
Published: March 2023

The mental illness tripled the risk of death during a searing 2021 heat wave, researchers find
The Feline Immunodeficiency Virus Envelope Signal Peptide Is a Tetherin Antagonizing Protein
Authors: Morrison James H. , Poeschla Eric M.
Published: March 2023

The study of species- and virus-specific differences in restriction factors and their antagonists has been central to deciphering the nature of these key host defenses. FIV is an AIDS-causing lentivirus that has achieved pandemic spread in the domestic cat.
Draft Genome Sequences of
Algoriphagus
sp. Strain PAP.12 and
Roseivirga
sp. Strain PAP.19, Isolated from Marine Samples from Papua, Indonesia
Authors: Riyanti  , Zumkeller Celine M. , Spohn Marius , Mihajlovic Sanja , Schwengers Oliver , Goesmann Alexander , Choironi Nur A. , Schäberle Till F. , Harwoko Harwoko
Published: March 2023

Algoriphagus
sp. strain PAP.12 (EXT111900) and
Roseivirga
sp. strain PAP.19 (EXT111901) were isolated from marine samples. Here, we report their draft genome sequences, 5.032 Mbp and 4.583 Mbp in size, respectively, and rate their specialized metabolite production capacity. Taxonomic ranks established by genome-based analysis indicate that
Algoriphagus
sp. strain PAP.12 represents a candidate new species.
Complete Genome Sequence of Bacteriophage vB_Hercules_Set, Which Infects Enteric Pathogen Salmonella enterica Serovar Typhimurium
Authors: Bennett Evan N. , Ayyash Ibrahim , Hughes Joshua , Comeau Teagen , Page Shallee T.
Published: March 2023

We report the isolation, sequencing, and annotation of bacteriophage vB_Hercules_Set, a kuttervirus infecting human pathogen
Salmonella enterica
. vB_Hercules_Set was isolated from a slurry of soil and deli meat collected in New Hampshire in 2021. The genome length is 157,338 nucleotides, containing 210 protein-coding genes and five tRNAs.
Computational Modeling of the Chlamydial Developmental Cycle Reveals a Potential Role for Asymmetric Division
Authors: Chiarelli Travis J. , Grieshaber Nicole A. , Appa Cody , Grieshaber Scott S.
Published: March 2023

Chlamydia trachomatis
is an obligate intracellular bacterial pathogen responsible for both ocular and sexually transmitted infections. All
Chlamydiae
are reliant on a complex developmental cycle, consisting of both infectious and noninfectious cell forms.
Clarifying Microbial Nitrous Oxide Reduction under Aerobic Conditions: Tolerant, Intolerant, and Sensitive
Authors: Wang Zhiyue , Vishwanathan Nisha , Kowaliczko Sophie , Ishii Satoshi
Published: March 2023

Some bacteria can reduce N
2
O in the presence of O
2
, whereas others cannot. It is unclear whether this trait of aerobic N
2
O reduction is related to the phylogeny and structure of N
2
O reductase.
Incidence of acute pancreatitis among patients with leptospirosis requiring extracorporeal membrane oxygenation (ECMO): a descriptive study
Authors: Madrigal Tristan Paulo R , Panlilio Mara Teresa T , Burog Aldrich Ivan Lois D , Danguilan Romina A , Chavez Joselito R
Published: March 2023

Background

Acute pancreatitis (AP) is an infrequently reported manifestation of leptospirosis. It is more commonly seen in patients with acute respiratory distress syndrome. Despite novel modalities such as extracorporeal membrane oxygenation (ECMO), the mortality rate remains high and whether this is associated with the lung injury caused by the inflammation in AP remains unclear.

Objectives and methods

A descriptive study was conducted at a tertiary hospital in the Philippines. Primary outcome was defined as the presence or absence of AP. Secondary outcomes were defined as 28-day mortality rate, length of hospital stay, ECMO days, renal replacement therapy (RRT) days, days on mechanical ventilation, presence of local complications of AP and development of nosocomial infections.

Results

A total of 27 patients were included in the study, and 88.89% (n=24) were men. The mean age for all patients was 33.59±10.22 years. Out of the 27 patients, 19 (70.37%) were diagnosed with AP. Among these 19 patients, one (5.26%) had necrotising pancreatitis and two (10.52%) developed local complications of pancreatitis. Six patients (31.58%) died among those who developed AP, while one (12.50%) died among those who did not. The duration of hospital stay, ECMO, RRT, mechanical ventilation and development of nosocomial infections was also higher in the group who presented with AP.

Conclusion

AP is an under-reported complication of leptospirosis. Our study demonstrated a higher mortality and morbidity in patients with leptospirosis who developed AP.
Impact ofHelicobacter pylorion the gastric microbiome in patients with chronic gastritis: a systematic review and meta-analysis protocol
Authors: Cao Xinyuan , Yang Yingyun , Zhang Yizhen , Ji Ruoyu , Zhao Xinyu , Zheng Weiyang , Yang Aiming
Published: March 2023

Introduction

Chronic gastritis is a common disease worldwide. Studies have consistently shown that chronic gastritis is usually associated with gastric microbial dysbiosis, especially the infection ofHelicobacter pylori. However, the interaction betweenH. pyloriand non-H. pyloribacteria in patients with chronic gastritis has not been clearly identified yet. Consequently, we designed a protocol for a systematic review and meta-analysis, which focused on identifying the changes in gastrointestinal microbiota composition between patients withH. pylori-infective and non-infective chronic gastritis.

Method and analysis

We will search PubMed, EMBASE and Cochrane Library databases to retrieve observational studies on humans. The eligible studies must include data about the relative abundance of the gastrointestinal microbiome in patients withH. pylori-infective or non-infective chronic gastritis. Only the data of adults aged over 18 years will be analysed. Two researchers will extract the data independently, and Newcastle–Ottawa Scale will be used to assess the risk of bias. Random-effects model will be performed in quantitative analyses. Correlation analysis, bioinformatics analysis and function analysis will be performed.

Discussion

Currently, numerous studies have revealed the role ofH. pyloriin chronic gastritis. However, the alterations of non-H. pyloribacteria in patients with chronic gastritis remain an open question. The results of our study might provide new insights into future diagnosis and treatments.

Ethics and dissemination

This study is based on published documents, unrelated to personal data, so ethical approval is not in need. The results of this study are expected to be published in journals or conference proceedings.

PROSPERO registration number

CRD42020205260; Pre-results.
Factors influencing influenza, pneumococcal and shingles vaccine uptake and refusal in older adults: a population-based cross-sectional study in England
Authors: Tan Pui San , Patone Martina , Clift Ashley Kieran , Dambha-Miller Hajira , Saatci Defne , Ranger Tom A , Garriga Cesar , Zaccardi Francesco , Shah Baiju R , Coupland Carol , Griffin Simon J , Khunti Kamlesh , Hippisley-Cox Julia
Published: March 2023

Objectives

Uptake of influenza, pneumococcal and shingles vaccines in older adults vary across regions and socioeconomic backgrounds. In this study, we study the coverage and factors associated with vaccination uptake, as well as refusal in the unvaccinated population and their associations with ethnicity, deprivation, household size and health conditions.

Design, setting and participants

This is a cross-sectional study of adults aged 65 years or older in England, using a large primary care database. Associations of vaccine uptake and refusal in the unvaccinated with ethnicity, deprivation, household size and health conditions were modelled using multivariable logistic regression.

Outcome measure

Influenza, pneumococcal and shingles vaccine uptake and refusal (in the unvaccinated).

Results

This study included 2 054 463 patients from 1318 general practices. 1 711 465 (83.3%) received at least one influenza vaccine, 1 391 228 (67.7%) pneumococcal vaccine and 690 783 (53.4%) shingles vaccine. Compared with White ethnicity, influenza vaccine uptake was lower in Chinese (OR 0.49; 95% CI 0.45 to 0.53), ‘Other ethnic’ groups (0.63; 95% CI 0.60 to 0.65), black Caribbean (0.68; 95% CI 0.64 to 0.71) and black African (0.72; 95% CI 0.68 to 0.77). There was generally lower vaccination uptake among more deprived individuals, people living in larger household sizes (three or more persons) and those with fewer health conditions. Among those who were unvaccinated, higher odds of refusal were associated with the black Caribbean ethnic group and marginally with increased deprivation, but not associated with higher refusal in those living in large households or those with lesser health conditions.

Conclusion

Certain ethnic minority groups, deprived populations, large households and 'healthier' individuals were less likely to receive a vaccine, although higher refusal was only associated with ethnicity and deprivation but not larger households nor healthier individuals. Understanding these may inform tailored public health messaging to different communities for equitable implementation of vaccination programmes.
Contribution of coping style to the association between illness uncertainty and demoralisation in patients with breast cancer: a cross-sectional mediation analysis
Authors: Hao Ran , Zhang Meng , Zuo Jinfan , Qi Yixin , Hu Jie
Published: March 2023

Objective

Demoralisation is a common psychological issue in patients with cancer and aggravates depression, reduces the quality of life and even causes suicidal ideation. There is a lack of knowledge about illness uncertainty, coping style and demoralisation in patients with breast cancer. The current study explored the relationship between illness uncertainty and demoralisation among those patients, as well as the potential mediating role of coping style.

Design

A cross-sectional study.

Setting

Participants were recruited from the Breast Tumor Center in a tertiary hospital in Shijiazhuang, Hebei province.

Participants

A total of 211 patients with breast cancer completed the survey.

Outcome measures

A total of 211 patients with breast cancer completed the Mishel’s Uncertainty in Illness Scale, Trait Coping Style Questionnaire and the Mandarin version of Demoralization Scale (DS-MV).

Results

Of the patients, 47.40% exhibited symptoms of demoralisation (DS-MV>30), and the mean of demoralisation score was (29.55±13.21). The results demonstrated that illness uncertainty and negative coping styles were positively related to demoralisation (p<0.001), while active coping styles were negatively related to demoralisation (p<0.001). Importantly, coping styles could partially mediate the relationship between illness uncertainty and demoralisation (p<0.01).

Conclusion

Our study illustrated that illness uncertainty was associated with demoralisation in patients with breast cancer, and coping style acted as a mediator in this relationship. The findings highlighted the critical role of reducing negative coping styles to the early prevention and efﬁcient treatment of demoralisation among those patients.
Combining chemotherapy and tislelizumab with preoperative split-course hypofraction radiotherapy for locally advanced rectal cancer: study protocol of a prospective, single-arm, phase II trial
Authors: Zheng Rong , Wang Bi-Si , Li Zhihua , Chi Pan , Xu Benhua
Published: March 2023

Introduction

Short-course radiotherapy (SCRT) with systemic therapy has the potential to further improve the long-term efficacy in patients with locally advanced rectal cancer (LARC). To maximise the benefits of neoadjuvant therapy for improved prognosis, it is important to determine the optimal mix of chemotherapy, immunotherapy and SCRT.

Methods and analysis

Fifty treatment-naïve patients with operable LARC (T3–4 and/or N+) will be recruited. Patients will be synchronously treated with capecitabine plus oxaliplatin (CAPOX) chemotherapy, tislelizumab and preoperative split-course hypofraction radiotherapy (SCHR) (5×7 Gy) before surgery. Chemotherapy for CAPOX starts on day 1 of every 21-day cycle: on day 1, oxaliplatin 130 mg/m2will be injected intravenously. On days 1–14, capecitabine 1000 mg/m2was ingested two times a day. Simultaneously, tocilizumab 200 mg will be given intravenously on the first day of every 21-day cycle. A single 7 Gy SCHR treatment (day 7 of each 21-day cycle) will be delivered five times during the seventh day of treatment. The primary endpoint will be pathological complete response. The secondary outcomes will be the 3-year disease-free survival, local recurrence rate, overall survival, sphincter-sparing surgery rate, R0 resection rate, predictive biomarkers and quality of life.

Ethics and dissemination

The study protocol was approved by the Ethics Committee of Xiehe Affiliated Hospital of Fujian Medical University (XAHFMU) (No. 2021YF025-01). Results from our study will be disseminated in international peer-reviewed journals. All study procedures were developed in order to assure data protection and confidentiality.

Trial registration number

NCT05176964.
Identification of the elements of models of antimicrobial resistance of bacteria for assessing their usefulness and usability in One Health decision making: a protocol for scoping review
Authors: Acharya Kamal Raj , Romero-Leiton Jhoana P , Parmley Elizabeth Jane , Nasri Bouchra
Published: March 2023

Introduction

Antimicrobial resistance (AMR) is a complex problem that requires the One Health approach, that is, a collaboration among various disciplines working in different sectors (animal, human and environment) to resolve it. Mathematical and statistical models have been used to understand AMR development, emergence, dissemination, prediction and forecasting. A review of the published models of AMR will help consolidate our knowledge of the dynamics of AMR and will also facilitate decision-makers and researchers in evaluating the credibility, generalisability and interpretation of the results and aspects of AMR models. The study objective is to identify and synthesise knowledge on mathematical and statistical models of AMR among bacteria in animals, humans and environmental compartments.

Methods and analysis

Eligibility criteria: Original research studies reporting mathematical and statistical models of AMR among bacteria in animal, human and environmental compartments that were published until 2022 in English, French and Spanish will be included in this study. Sources of evidence: Database of PubMed, Agricola (Ovid), Centre for Agriculture and Bioscience Direct (CABI), Web of Science (Clarivate), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and MathScinet. Data charting: Metadata of the study, the context of the study, model structure, model process and reporting quality will be extracted. A narrative summary of this information, gaps and recommendations will be prepared and reported in One Health decision-making context.

Ethics and dissemination

Research ethics board approval was not obtained for this study as neither human participation nor unpublished human data were used in this study. The study findings will be widely disseminated among the One Health Modelling Network for Emerging Infections network and stakeholders by means of conferences, and publication in open-access peer-reviewed journals.
Common health assets protocol: a mixed-methods, realist evaluation and economic appraisal of how community-led organisations (CLOs) impact on the health and well-being of people living in deprived areas
Authors: Baker Rachel Mairi , Ahmed Mohasin , Bertotti Marcello , Cassidy John , Chipuriro Rejoice , Clewett Emma , Donaldson Cam , Elders Andrew , Fenge Lee Ann , Fox Julie , Galway Karen , Gildea Aideen , McGuinness Aileen , McLean Jennifer , Manoukian Sarkis , Mason Helen , Morgan Antony , Mulholland Jill , O'Hare Liam , Paterson Andrew , Porter Sam , Rendall Jack , Roy Michael J , Seaman Peter , Simpson Merron , Steiner Artur , Kelly Michael P
Published: March 2023

Introduction

This research investigates how community-led organisations’ (CLOs’) use of assets-based approaches improves health and well-being, and how that might be different in different contexts. Assets-based approaches involve ‘doing with’ rather than ‘doing to’ and bring people in communities together to achieve positive change using their own knowledge, skills and experience. Some studies have shown that such approaches can have a positive effect on health and well-being. However, research is limited, and we know little about which approaches lead to which outcomes and how different contexts might affect success.

Methods and analysis

Using a realist approach, we will work with 15 CLOs based in disadvantaged communities in England, Scotland and Northern Ireland. A realist synthesis of review papers, and a policy analysis in different contexts, precedes qualitative interviews and workshops with stakeholders, to find out how CLOs’ programmes work and identify existing data. We will explore participants’ experiences through: a Q methodology study; participatory photography workshops; qualitative interviews and measure outcomes using a longitudinal survey, with 225 CLO participants, to assess impact for people who connect with the CLOs. An economic analysis will estimate costs and benefits to participants, for different contexts and mechanisms. A ‘Lived Experience Panel’ of people connected with our CLOs as participants or volunteers, will ensure the appropriateness of the research, interpretation and reporting of findings.

Ethics and dissemination

This project, research tools and consent processes have been approved by the Glasgow Caledonian University School of Health and Life Sciences Ethics Committee, and affirmed by Ethics Committees at Bournemouth University, Queen’s University Belfast and the University of East London. Common Health Assets does not involve any National Health Service sites, staff or patients.

Findings will be presented through social media, project website, blogs, policy briefings, journal articles, conferences and visually in short digital stories, and photographic exhibitions.
Categorising implementation determinants and strategies within the US HIV implementation literature: a systematic review protocol
Authors: Merle James Lorenz , Li Dennis , Keiser Brennan , Zamantakis Alithia , Queiroz Artur , Gallo Carlos G , Villamar Juan A , McKay Virginia , Zapata Juan Pablo , Mustanski Brian , Benbow Nanette , Smith Justin D
Published: March 2023

Introduction

Despite decreased rates of new infections, HIV/AIDS continues to impact certain US populations. In order to achieve the goals laid out in the Ending the HIV Epidemic (EHE) in the US initiative, implementation science is needed to expand the sustained use of effective prevention and treatment interventions, particularly among priority populations at risk for and living with HIV/AIDS. Over 200 HIV-related implementation studies have been funded by the US National Institutes of Health. Therefore, a comprehensive review of the literature identifying implementation determinants (barriers and facilitators) and categorising implementation strategies across the continuum of HIV prevention and care in the USA is appropriate and needed to enhance current knowledge and help achieve the goals laid out in the EHE national strategic plan.

Methods and analysis

This systematic review protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Between November 2020 and January 2022, a broad database search strategy of Ovid MEDLINE, PsycINFO and Web of Science was conducted to capture implementation-related studies along the HIV prevention and care continuum. Articles were eligible for inclusion if they were: conducted in the USA, published after the year 2000, written in English, related to HIV/AIDS, focused on outcomes related to dissemination and implementation (ie, did not test/evaluate/explore implementation determinants or strategies) and were behavioural studies (ie, not basic science). We plan to conduct three systematic reviews to identify and categorise determinants and strategies associated with three HIV focus areas: pre-exposure prophylaxis, testing/diagnosing and linkage to care, and treatment. Determinants will be coded according to an adapted Consolidated Framework for Implementation Research 2.0. Implementation strategies and outcomes will be categorised in accordance with existing taxonomies and frameworks.

Ethics and dissemination

Ethics approval is not applicable. No original data will be collected. Results will be disseminated through peer-reviewed publications, conference presentations and via online tools.

PROSPERO registration number

CRD42021233089.
Risk of Aneurysm Rupture (ROAR) study: protocol for a long-term, longitudinal, UK multicentre study of unruptured intracranial aneurysms
Authors: Hall Samuel , Birks Jacqueline , Anderson Ian , Bacon Andrew , Brennan Paul M , Bennett David , Chavredakis Emmanuel , Critchley Giles , Dow Graham , Downer Jonathan , Galea James , Grover Patrick , Gurusinghe Nihal , Helmy Adel , Kounin Gueorgui , Mukerji Nitin , Patel Hiren , Patel Jash , Ross Nicholas , St George Jerome , Teo Mario , Tolias Christos Michael , Tzerakis Nikolaos , Uff Christopher , van Beijum Janneke , Veighey Kristin , White Edward , Whitfield Peter , Bulters Diederik Oliver
Published: March 2023

Introduction

Unruptured intracranial aneurysms (UIA) are common in the adult population, but only a relatively small proportion will rupture. It is therefore essential to have accurate estimates of rupture risk to target treatment towards those who stand to benefit and avoid exposing patients to the risks of unnecessary treatment. The best available UIA natural history data are the PHASES study. However, this has never been validated and given the known heterogeneity in the populations, methods and biases of the constituent studies, there is a need to do so. There are also many potential predictors not considered in PHASES that require evaluation, and the estimated rupture risk is largely based on short-term follow-up (mostly 1 year). The aims of this study are to: (1) test the accuracy of PHASES in a UK population, (2) evaluate additional predictors of rupture and (3) assess long-term UIA rupture rates.

Methods and analysis

The Risk of Aneurysm Rupture study is a longitudinal multicentre study that will identify patients with known UIA seen in neurosurgery units. Patients will have baseline demographics and aneurysm characteristics collected by their neurosurgery unit and then a single aggregated national cohort will be linked to databases of hospital admissions and deaths to identify all patients who may have subsequently suffered a subarachnoid haemorrhage. All matched admissions and deaths will be checked against medical records to confirm the diagnosis of aneurysmal subarachnoid haemorrhage. The target sample size is 20 000 patients. The primary outcome will be aneurysm rupture resulting in hospital admission or death. Cox regression models will be built to test each of the study’s aims.

Ethics and dissemination

Ethical approval has been given by South Central Hampshire A Research Ethics Committee (21SC0064) and Confidentiality Advisory Group support (21CAG0033) provided under Section 251 of the NHS Act 2006. The results will be disseminated in peer-reviewed journals.

Trial registration number

ISRCTN17658526.
Healthcare experience of adults with COPD during the COVID-19 pandemic: a rapid review of international literature
Authors: Madawala Sanduni , Quach Anthony , Lim Jia Yi , Varatharaj Sanjay , Perera Bianca , Osadnik Christian , Barton Chris
Published: March 2023

Background

People living with chronic obstructive pulmonary disease (COPD) are a group who may be particularly vulnerable to COVID-19. This vulnerability has been associated with increased anxiety or fear about exposure to the virus, which may also impact upon experience in healthcare settings.

Aim/objectives

The aim of this narrative mixed-methods review was to systematically scope, identify and synthesise findings from peer-reviewed qualitative, quantitative and mixed-methods studies published in academic journals describing the healthcare experiences of adults living with COPD independently in the community, following the emergence of COVID-19 in December 2019–June 2022.

Methods

Databases including Ovid MEDLINE, PsychINFO, Ovid Emcare and CINAHL Plus were searched. Studies were uploaded to Covidence to support selection and appraisal of studies. Studies were appraised for quality using the Mixed Methods Appraisal Tool. A narrative synthesis of these themes was provided, and qualitative and quantitative findings are interpreted together in the discussion.

Findings

The quality and experience of care for patients with COPD was impacted through the COVID-19 pandemic. Innovations and adoption of technologies such as telehealth and telerehabilitation were well received and mitigated the potential implications of severe disruption to care access to some extent. Patients feared feeling forgotten and experienced isolation and anxiety; however, telerehabilitation and exercise through modalities such as Zoom classes help support social connection and physical activity.

Implications

These innovations are likely to be useful to be offered to patients on an ongoing basis, and education and standardised protocols around their use will benefit healthcare providers and patients alike.

PROSPERO registration number

CRD42022341168.
Eating behaviours, menstrual history and the athletic career: a retrospective survey from adolescence to adulthood in female endurance athletes
Authors: Ravi Suvi , Valtonen Maarit , Ihalainen Johanna K , Holopainen Elina , Kosola Silja , Heinonen Saara , Waller Ben , Kujala Urho M , Parkkari Jari
Published: March 2023

Aim

To evaluate differences in menstrual and pubertal history and trends in eating behaviours among women with and without a competitive sports background. Additionally, we investigated if menstrual history and eating behaviours are associated with sports career-related factors.

Methods

This retrospective study was conducted on 100 women with a competitive endurance sports background and their age-matched, gender-matched and municipality-matched controls (n=98). Data were collected using a questionnaire using previously validated instruments. Generalised estimating equations were used to calculate associations of menstrual history and eating behaviours with outcome variables (career length, participation level, injury-related harms and career termination due to injury).

Results

Athletes reported higher rates of delayed puberty and menstrual dysfunction than controls. No differences between the groups were observed in the Eating Disorder Examination Questionnaire short form (EDE-QS) scores at any age. Previous disordered eating (DE) was associated with current DE in both groups. Among athletes, higher EDE-QS scores during the sports career were associated with a shorter career (B=−0.15, 95% CI −0.26 to –0.05). Secondary amenorrhoea was associated with lower participation level (OR 0.51, 95% CI 0.27 to 0.95), injury-related harms during the career (OR 4.00, 95% CI 1.88 to 8.48) and career termination due to injury (OR 1.89, 95% CI 1.02 to 3.51).

Conclusion

The findings indicate that DE behaviours and menstrual dysfunction, specifically secondary amenorrhoea, have a disadvantageous relationship with a sports career in women competing in endurance sports. DE during the sports career is associated with DE after the career.
Associations between health problems and athlete burnout: a cohort study in 210 adolescent elite athletes
Authors: Moseid Nils Fredrik Holm , Lemyre Nicolas , Roberts Glyn C , Fagerland Morten Wang , Holm Moseid Christine , Bahr Roald
Published: March 2023

Objectives

We studied associations between the burden of health problems and athlete burnout in a population of athletes from Norwegian Sport Academy High Schools.

Methods

This is a mixed prospective/retrospective cohort study. We included 210 athletes, 135 boys and 75 girls, from endurance, technical and team sports. We used the Oslo Sports Trauma Centres Questionnaire for Health Problems to collect 124 weeks of health data. During the first 26 weeks, athletes reported the health data prospectively using a smartphone app. For the following 98 weeks, we collected health data by interviewing athletes at the end of their third year in Sport Academy High School. At the time of the interview, the athletes also completed a web-based questionnaire, including the Athlete Burnout Questionnaire and covering social relations in sports and school, coach relations and living conditions.

Results

A greater burden of health problems was associated with a higher score for athlete burnout (B: 0.16, 95% CI 0.09 to 0.22, p<0.001). In a multivariable model, this was true for both illnesses (B: 0.21, 95% CI 0.10 to 0.32, p<0.001), acute injuries (B: 0.16, 95% CI 0.04 to 0.27, p=0.007) and overuse injuries (B: 0.10, 95% CI 0.002 to 0.18, p=0.011). This was also true in gender and sports category subgroups. The coach having a high influence on training week was associated with a lower score for athlete burnout.

Conclusion

A greater burden of health problems was associated with greater symptoms of athlete burnout in athletes attending Sport Academy High Schools.
Rheumatic heart disease mortality in Indigenous and non-Indigenous Australians between 2013 and 2017
Authors: Stacey Ingrid , Seth Rebecca , Nedkoff Lee , Hung Joseph , Wade Vicki , Haynes Emma , Carapetis Jonathan , Murray Kevin , Bessarab Dawn , Katzenellenbogen Judith M
Published: March 2023

Objectives

To generate contemporary age-specific mortality rates for Indigenous and non-Indigenous Australians aged <65 years who died from rheumatic heart disease (RHD) between 2013 and 2017, and to ascertain the underlying causes of death (COD) of a prevalent RHD cohort aged <65 years who died during the same period.

Methods

For this retrospective, cross-sectional epidemiological study, Australian RHD deaths for 2013–2017 were investigated by first, mortality rates generated using Australian Bureau of Statistics death registrations where RHD was a coded COD, and second COD analyses of death records for a prevalent RHD cohort identified from RHD register and hospitalisations. All analyses were undertaken by Indigenous status and age group (0–24, 25–44, 45–64 years).

Results

Age-specific RHD mortality rates per 100 000 were 0.32, 2.63 and 7.41 among Indigenous 0–24, 25–44 and 45–64 year olds, respectively, and the age-standardised mortality ratio (Indigenous vs non-Indigenous 0–64 year olds) was 14.0. Within the prevalent cohort who died (n=726), RHD was the underlying COD in 15.0% of all deaths, increasing to 24.6% when RHD was included as associated COD. However, other cardiovascular and non-cardiovascular conditions were the underlying COD in 34% and 43% respectively.

Conclusion

Premature mortality in people with RHD aged <65 years has approximately halved in Australia since 1997–2005, most notably among younger Indigenous people. Mortality rates based solely on underlying COD potentially underestimates true RHD mortality burden. Further strategies are required to reduce the high Indigenous to non-Indigenous mortality rate disparity, in addition to optimising major comorbidities that contribute to non-RHD mortality.
Comparative effect of varenicline and nicotine patches on preventing repeat cardiovascular events
Authors: Robijn Annelies L , Filion Kristian B , Woodward Mark , Hsu Benjumin , Chow Clara K , Pearson Sallie-Anne , Jorm Louisa , Falster Michael O , Havard Alys
Published: March 2023

Objective

To determine the comparative effectiveness of postdischarge use of varenicline versus prescription nicotine replacement therapy (NRT) patches for the prevention of recurrent cardiovascular events and mortality and whether this association differs by sex.

Methods

Our cohort study used routinely collected hospital, pharmaceutical dispensing and mortality data for residents of New South Wales, Australia. We included patients hospitalised for a major cardiovascular event or procedure 2011–2017, who were dispensed varenicline or prescription NRT patches within 90day postdischarge. Exposure was defined using an approach analogous to intention to treat. Using inverse probability of treatment weighting with propensity scores to account for confounding, we estimated adjusted HRs for major cardiovascular events (MACEs), overall and by sex. We fitted an additional model with a sex–treatment interaction term to determine if treatment effects differed between males and females.

Results

Our cohort of 844 varenicline users (72% male, 75% <65 years) and 2446 prescription NRT patch users (67% male, 65% <65 years) were followed for a median of 2.93 years and 2.34 years, respectively. After weighting, there was no difference in risk of MACE for varenicline relative to prescription NRT patches (aHR 0.99, 95% CI 0.82 to 1.19). We found no difference (interaction p=0.098) between males (aHR 0.92, 95% CI 0.73 to 1.16) and females (aHR 1.30, 95% CI 0.92 to 1.84), although the effect among females deviated from the null.

Conclusion

We found no difference between varenicline and prescription NRT patches in the risk of recurrent MACE. These results should be considered when determining the most appropriate choice of smoking cessation pharmacotherapy.
TFAM deficiency in dendritic cells leads to mitochondrial dysfunction and enhanced antitumor immunity through cGAS-STING pathway
Authors: Lu Tianqi , Zhang Ziqi , Bi Zhenfei , Lan Tianxia , Zeng Hao , Liu Yu , Mo Fei , Yang Jingyun , Chen Siyuan , He Xuemei , Hong Weiqi , Zhang Zhe , Pi Ruyu , Ren Wenyan , Tian Xiaohe , Wei Yuquan , Luo Min , Wei Xiawei
Published: March 2023

Background

Mitochondrial transcription factor A (TFAM) is a transcription factor that maintains mitochondrial DNA (mtDNA) stabilization and initiates mtDNA replication. However, little is known about the immune regulation function and TFAM expression in immune cells in the tumors.

Methods

Mouse tumor models were applied to analyze the effect of TFAM deficiency in myeloid cell lineage on tumor progression and tumor microenvironment (TME) modification. In vitro, primary mouse bone marrow-derived dendritic cells (BMDCs) were used in the investigation of the altered function and the activated pathway. OVA was used as the model antigen to validate the activation of immune responses in vivo. STING inhibitors were used to confirm the STING activation provoked byTfamdeficient in DCs.

Results

The deletion of TFAM in DCs led to mitochondrial dysfunction and mtDNA cytosolic leakage resulting in the cGAS-STING pathway activation in DCs, which contributed to the enhanced antigen presentation. The deletion of TFAM in DCs has interestingly reversed the immune suppressive TME and inhibited tumor growth and metastasis in tumor models.

Conclusions

We have revealed that TFAM knockout in DCs ameliorated immune-suppressive microenvironment in tumors through STING pathway. Our work suggests that specific TFAM knockout in DCs might be a compelling strategy for designing novel immunotherapy methods in the future.
Systemic inflammatory syndromes as life-threatening side effects of immune checkpoint inhibitors: case report and systematic review of the literature
Authors: Liu Lisa L , Skribek Marcus , Harmenberg Ulrika , Gerling Marco
Published: March 2023

Immune checkpoint inhibitors (ICIs) are associated with a wide range of immune-related adverse events. As oncological indications for ICIs widen, their rare side effects become increasingly visible in clinical practice and impact therapy decisions.

Here, we report a rare case of early-onset, mild cytokine release syndrome (CRS) in a patient who received ICIs for a metastasized renal cell carcinoma, which led to treatment discontinuation.

We further provide a systematic review of the literature of CRS and related life-threatening side effects of ICI treatment, such as hemophagocytic lymphohistiocytosis (HLH). We searched Medline, Embase and the Web of Science Core Collection from inception to October 2021 for reports on CRS, cytokine storm, macrophage activation syndrome, HLH, and related hyperinflammatory disorders in patients with solid cancers receiving ICIs. We found n=1866 articles, which were assessed for eligibility independently by two examiners. Of those, n=49 articles reporting on n=189 individuals were eligible for review. We found that the median time from last infusion to the occurrence of CRS/HLH was approximately nine days, while the onset of symptoms varied from immediately after infusion to one month after treatment. Most patients were treated with either corticosteroids or the anti-interleukin 6 (IL-6) antibody tocilizumab, and although the majority of patients recovered, a few cases were fatal. Concomitant IL-6 and ICI treatment were reported as beneficial for both the antitumoral effect and for limiting side effects. Data from international pharmacovigilance databases underscored that ICI-related CRS and HLH are rare events, but we identified significant differences in reported frequencies, which might suggest substantial under-reporting.

The results from this first systematic review of CRS/HLH due to ICI therapy highlight that life-threatening systemic inflammatory complications of ICIs are rare and might be associated with fatal outcome in approximately 10% of patients. Limited data support the use of IL-6 inhibitors in combination with ICIs to augment the antitumoral effect and reduce hyperinflammation.
Implication of99mTc-sum IL-2 SPECT/CT in immunotherapy by imaging of tumor-infiltrating T cells
Authors: Gao Yu , Luo Qi , Sun Zhichen , Gao Hannan , Yu Yue , Sun Yining , Ma Xiaotu , Han Chuanhui , Shi Jiyun , Wang Fan
Published: March 2023

Background

Although immune checkpoint blockade (ICB) and adoptive T cell transfer (ACT) therapy have achieved impressive clinical outcomes, majority of patients do not respond to immunotherapy. Tumor-infiltrating T cells, a critical factor to immunotherapy, is dynamically changing. Therefore, a reliable real-time in vivo imaging system for tumor-infiltrating T cells, but not immunohistochemical analyses, will be more valuable to predict response and guide immunotherapy. In this study, we developed a new SPECT/CT imaging probe99mTc-sum IL-2 targeting the IL-2Rβ/IL-2Rγ (CD122/CD132) receptor on tumor-infiltrating T cells, and evaluated its application in predicting the immune response to anti-PD-L1 (αPD-L1) therapy as well as tracking infused T cells in ACT therapy.

Methods

The binding affinity of the super mutated IL-2 (sum IL-2) in various T cell subtypes was measured. Sum IL-2 was subsequently labeled with99mTc through Sortase-A mediated site-specific transpeptidation. SPECT/CT imaging and biodistribution studies of99mTc-sum IL-2 were performed in a MC38 mouse model. Wild type IL-2 (IL-2) was used as control in the above studies. Finally, we evaluated99mTc-sum IL-2 SPECT/CT for the detection of tumor-infiltrating T cells in the context of αPD-L1 immunotherapy and ACT therapy.

Results

Sum IL-2 preferentially bound to CD8+T cells, especially activated CD8+T cells, while IL-2 showed biased binding to Treg cells. As a result,99mTc-sum IL-2 could detect tumor-infiltrating T cells. In the MC38 tumor model, SPECT/CT imaging showed the increased tumor uptake of99mTc-sum IL-2 after αPD-L1 treatment, suggesting that the treatment significantly increased tumor-infiltrating T cells, resulting in a correspondingly significant curative effect. In addition,99mTc-sum IL-2 SPECT/CT could also track the infiltration of antigen-specific cytotoxic CD8+T cells during ACT therapy.

Conclusion

99mTc-sum IL-2 has great clinical potential for non-invasive and specific SPECT/CT imaging of tumor-infiltrating T cells as well as for timely prediction and evaluation of the therapeutic efficacy of ICB and ACT therapy.