bluuebunny/crossref_metadata_2025 huggingface dataset:
Tectonic history of the Mesoproterozoic Coal Creek serpentinite, Llano Uplift, central Texas, USA
Authors: Mosher Sharon , Gillis Gretchen
Published: January 2025

The Llano Uplift Coal Creek serpentinite is one of few exposed Grenville-age ultramafic rocks and is an important element in reconstructing the tectonic history of the Grenville orogeny in Texas, USA. During Grenville-age collisional orogenesis, the ultramafic harzburgite protolith underwent dynamothermal prograde metamorphism, which resulted in partial to complete serpentinization during emplacement, deserpentinization during subsequent regional high-temperature, medium-pressure metamorphism, and continued post-kinematic metamorphism. An unrelated late (post-Grenville) serpentinization occurred when the ultramafic rocks were exposed near or at the surface.

Disequilibrium assemblages and structural fabrics allow the pressure−temperature−time path to be estimated with peak conditions ranging between 685 °C and 810 °C and pressures of 0.8−1 GPa. Although most of the serpentinite has been replaced by lizardite, layers of incompletely replaced olivine and enstatite have metamorphic chemistries and are truncated by randomly oriented anthophyllite. Foliated metasomatic blackwall zones of tremolite, Mg chlorite, talc, and magnetite have a continuous foliation with the adjacent serpentinite.

Tectonic emplacement of the serpentinite with a northward vergence occurred early in the deformational history of the Llano Uplift. The serpentinite was structurally imbricated with an exotic ensimatic arc and most likely represents the mantle portion of an obducted ophiolite. The serpentinite and ensimatic arc underwent deformation and regional amphibolite facies metamorphism together as a package, necessitating the overriding of some southern continental block. This polyphase deformational and metamorphic history is similar to the rest of the southeastern uplift and consistent with continent-arc-continent collision. The Texas Grenville-aged tectonic history provides an unambiguous record of Mesoproterozoic orogenic events not obscured by any older or younger orogeny.
The two-sided continental subduction of the Adria microplate (Mediterranean)
Authors: Menichelli Irene , De Gori Pasquale , Funiciello Francesca , Claudio Chiarabba
Published: January 2025

The recycling of the continental lithosphere back into the mantle significantly impacts the structure and dynamics of orogens, particularly in the central Mediterranean region. We demonstrate that variations in the rheological properties of the continental lithosphere, as revealed by high-resolution regional tomography, influence the style of continental subduction. We explain the geometry and evolution of the oppositely verging Apennines and Dinarides orogens, as given by contrasting subduction processes, such as underplating and continental delamination, affecting the same plate (the Adriatic microplate, or Adria). In the case of the Apennines, slab peel-back predominates during subduction, resulting in a steeply dipping slab. In contrast, the Dinarides experience flat subduction due to the underplating of continental material. These different mechanisms, influencing kinematics and surface processes, are governed by rheological heterogeneities and different buoyancies of the continental lithosphere.
Sarcomatoid carcinoma of small intestine
Authors: Hoseini Sayed Shahabuddin , Tang Xiaoyu , Dewar Rajan
Published: January 2025

Sarcomatoid carcinoma is a rare type of tumour consisting of neoplastic cells expressing both epithelial and mesenchymal cell markers. The small intestine is a rare site for sarcomatoid carcinoma and to date, a few cases have been reported. In this manuscript, a case of jejunal sarcomatoid carcinoma in a man in his 50s is reported. A review of the literature on sarcomatoid carcinomas of small bowel is presented.
Undiagnosed partial ornithine transcarbamylase deficiency presenting as recurrent hyperammonaemic encephalopathy after capecitabine administration
Authors: Giglio Robert Spencer , Kiser Brandon , Dang Anthony
Published: January 2025

Capecitabine is a widely used drug for cancer treatment. Capecitabine is a derivative of 5-fluorouracil (5-FU). A known complication of 5-FU is hyperammonaemia which can cause encephalopathy. To our knowledge, there are very few documented cases demonstrating hyperammonaemia associated with capecitabine. There are also cases suggesting capecitabine improves hyperammonaemia from 5-FU. We present the case of an older man taking capecitabine, who presented to our hospital with severe encephalopathy with elevated ammonia. Workup led to the diagnosis of a urea cycle disorder. This case highlights the importance of determining the aetiology of a patient’s presentation, especially if they have presented repeatedly with the same issue. It is important to think of common causes first; however, we must broaden the differential diagnoses when the simple answer does not explain the clinical picture.
Surgical revascularisation in an adult with coarctation of the aorta
Authors: Joseph Jocilin , Swarna Sindhu , Pai Suraj
Published: January 2025

One of the most common congenital cardiac anomalies iscoarctation of the aorta (CoA). It accounts for 4%–6% of all congenital heart defects. A CoA case surviving into adulthood may result in hypertension, weak femoral pulse, limb and bowel ischaemia and heart failure. A man in his early 20s presented with severe lower limb and abdominal pain with long-standing hypertension, refractory to antihypertensives. Difference in upper and lower limb blood pressures, weak peripheral pulses and radiofemoral delay were noted. Angiogram showed adult CoA with total occlusion of the proximal aortic segment. The patient underwent left axillary artery to descending thoracic aorta bypass grafting, had a normal recovery and was put on life-long antihypertensives. An untreated case of CoA surviving into adulthood will result in complications. Any individual with unknown aetiology of hypertension and ischaemic symptoms must be screened for CoA.
Growing old before growing rich: a scoping review on ageing-related policy interventions from the WHO Southeast Asian Region
Authors: Mohan Anu , Jaihind Jothikaran Teddy Andrews , Gudi Nachiket , A K Abhijith , Ashok Lena
Published: January 2025

Background

WHO Southeast Asian Region (WHO SEARO) is home to 1.94 billion people accounting for one-fourth of the global population.

Objective

The primary objective of this scoping review is to describe the various policy interventions implemented in countries of the WHO SEARO to address the consequences of ageing.

Design

The Arksey and O’Malley framework for scoping review was used to explore existing policy interventions on aged care.

Setting

WHO SEARO.

Methods

Ten articles and 33 grey literature discussing the various aged care interventions adopted by WHO SEARO countries were identified through a comprehensive search performed across five databases, PubMed (NCBI), Embase (Elsevier), Web of Science (Clarivate) and Scopus (Elsevier) and Google Scholar.

Results

The review indicates that healthcare, long-term care and rehabilitation, maintenance and welfare, and old age social security are the critical domains of existing policy intervention. The grey literature, including policies, acts, legislations, agendas and plans of action adopted by WHO SEARO countries, concludes that existing interventions are spread across the differential aspects of ageing and aged care. The notable delimitations of the given policy interventions are ambiguity regarding the monitoring of the programmes, lack of benchmark standards for evaluation of progress, inadequate attention to rural poverty and lack of decentralisation.

Conclusion

WHO SEARO countries can respond better to ageing by reinforcing areas such as caregiver support and allowances, public financing in older care, old age health insurance, public-private partnership in mobile and institutional caring and social security systems including old age and disability pension.
Knowledge of COVID-19 and the psychological status of parents: a retrospective survey in Wuhan, Hubei
Authors: Wang Lei , Gan Honghui , Zhang Yutong , Xiong Change , Wang Guiping , Mei Can , Chen Linwanyue , Xu Yaqi , He Lu , Lv Lin , Pan Shuliu , Zhan Jianbo , Cheng Jing
Published: January 2025

Objective

During the COVID-19 pandemic, many parents faced heightened stress, anxiety and depression due to the local and global COVID-19 mitigation measures and lockdowns.

Design

This is a cross-sectional study.

Setting

This study used stratified whole-cluster sampling to randomly select three elementary schools within Ezhou City.

Participants

An online survey was administered to the parents of students in one or two classes in grades 1–6, respectively, of each school. Among them, males account for 30.4% and females account for 69.6%. The inclusion criteria included (1) the parent or legal guardian of a primary school student or a person directly responsible for the child’s education and (2) the ability to operate a computer or smartphone to complete the survey. Only one representative from each family was allowed to participate, and surveys with incomplete data were considered invalid and thus excluded.

Results

A total of 764 participants completed the online survey. Overall, 90.4% of the participants were concerned about their children’s mental health and learning during the pandemic. Additionally, 97.0% were aware of the typical symptoms of COVID-19. Only 48.0% of the participants felt the pandemic negatively impacted their lives. The average psychological status score among parents was 87.79±8.91, with 51.6% showing signs of high psychological distress. Significant differences in psychological status were linked to age, education, professional background, sleep status, personal views on the pandemic’s impact and concern for children’s learning (p<0.05). Multiple logistic regression analysis revealed that a negative perception of the pandemic’s impact on one’s life (OR 0.367, 95% CI: 0.272 to 0.493) was associated with psychological distress.

Conclusion

Parents of school children in Ezhou City have a good knowledge base on COVID-19 infection and have a high awareness of the corresponding protective measures. However, priority attention and care should be given to individuals who have experienced mental distress in relation to the pandemic.
Individual and community level maternal factors for zero-dose children in Ethiopia using mini-EDHS 2019: a mixed effects model
Authors: Agimas Muluken Chanie , Alemayehu Meron Asmamaw , Tesfie Tigabu Kidie , Tilahun Werkneh Melkie , Asferie Worku Necho , Aweke Mekuriaw Nibret , Abebe Moges Tadesse , Yalew Anteneh Kassa
Published: January 2025

Introduction

Zero-dose children refer to a child who has not yet received any childhood vaccines. Globally, zero-dose children are the major public health problem. In sub-Saharan African countries, one among five children do not have access to vaccines. But the efforts to identify the factors contributing to the zero-dose children are not well addressed in Ethiopia.

Objectives

To assess individual and community-level maternal factors of zero-dose children in Ethiopia using mini-Ethiopian Demographic Health Survey 2019.

Methods

A secondary analysis of a cross-sectional study was used among a total of 3208 participants. STATA-14 was used for descriptive and multilevel binary logistic regression (mixed effects model) analysis. Model selection was conducted using Akaike information criteria. To identify significant factors for zero-dose children, a p value of <0.05 with 95% CI was used.

Results

The prevalence of zero-dose children among children aged 12–35 months was 523 (16.3%, 95% CI 15% to 17.6%). Women with no antenatal care follow-up (adjusted OR (AOR)=1.55, 95% CI 1.02 to 2.35), uneducated women (AOR=1.47, 95% CI 1.11 to 1.95), women who gave birth at home (AOR=1.39, 95% CI 1.04 to 1.86), women who had poor wealth index (AOR=2.15, 95% CI 1.62 to 2.85) and women from low proportions of community media exposure (AOR=1.39, 95% CI 1.13 to 1.71) were the risk factors for zero-dose children in Ethiopia.

Conclusion

Compared with previous studies, the prevalence of zero-dose children was low in Ethiopia. Variables like urban residence, no education, home delivery, poor wealth index, no antenatal care(ANC) visit and women from low proportions of community media exposure were the risk factors for zero-dose children in Ethiopia. Therefore, expanding maternal health services and media access for women is highly recommended to reduce zero-dose children mortality.
Enhancing physical activity during pregnancy using a multi-theory model: a study protocol for a randomised controlled trial in China
Authors: Jin Ying , Zhang Wei , Zhang Le , Zhang Xuesong , Shen Yu , Liu Ningning , Feng Suwen
Published: January 2025

Background

Physical inactivity is a global concern and poses serious health risks. Physical inactivity is exacerbated and affects the health of both generations during the special period of pregnancy. Appropriate physical activity (PA) intervention programmes based on health behaviour change theory are lacking. This study aims to evaluate the effectiveness of a PA intervention based on the multi-theory model (MTM) by assessing changes in PA levels, MTM constructs, exercise self-efficacy, quality of life, prenatal depressive symptoms, gestational weight gain and pregnancy and delivery outcomes.

Methods and analysis

This single-centre, parallel, randomised, controlled trial will be conducted at a tertiary care institution in Hangzhou, China. A total of 72 pregnant women without contraindications to exercise at 14–27 weeks+6 days of gestation will be included. Participants will be randomly assigned to either the intervention or control group. The intervention group will engage in a 12 week PA intervention programme based on the MTM and delivered through WeChat, while the control group will receive standard antenatal care. Data will be collected at baseline, 6 weeks of the intervention, 12 weeks of the intervention and within 1 week of delivery. The primary outcomes will include PA levels measured by accelerometers and the PA in Pregnancy Questionnaire, along with the constructs of the MTM. Secondary outcomes will comprise exercise self-efficacy during pregnancy, quality of life, prenatal depressive symptoms, gestation weight gain and pregnancy and delivery outcomes. Data analysis will adhere to the Consolidated Standards of Reporting Trials 2010 statement and follow the intention-to-treat principle.

Ethics and dissemination

The study followed the ethical guidelines approved by the ethics committee of Women’s Hospital School of Medicine Zhejiang University (IRB-20230254-R, Approval Date: 27 July 2023). The results of the study will be submitted for publication and dissemination in a peer-reviewed journal. Participants will receive clarification regarding the study objectives, procedures and will be asked to sign informed consent in written form before the start of the study.

Trial registration number

ChiCTR2400080843. Prospectively registered on 8 February 2024.
mHealth-based intervention by community workers to support family caregivers of persons with dementia living at home: study protocol for a cluster randomised controlled trial
Authors: Bhardwaj Pankaj , Joshi Nitin Kumar , Gupta Manoj Kumar , Sharma Suresh K , Nebhinani Naresh , Sinha Abhik , Tyrrell Marie , Konradsen Hanne , Craftman Åsa G , Kabir Zarina Nahar
Published: January 2025

Background

India is undergoing a significant demographic shift with a growing older population, leading to an anticipated increase in people with dementia. Family caregivers, who are predominantly informal, carry the burden of care within households, facing numerous challenges that impact their well-being. Despite the cultural emphasis on family support, there is a lack of targeted interventions for caregivers in India. The WHO emphasises the importance of caregiver support, and recent advancements in information and communication technology, particularly mobile health (mHealth), offer promising avenues to address this need. This study protocol outlines an Indo-Sweden collaborative effort, funded by Indian Council of Medical Research (ICMR) Forte, to develop and assess the effectiveness of a mHealth application designed to improve caregiving skills, reduce caregiver burden and support family caregivers of persons with dementia.

Methods and analysis

The study will be conducted through a community-based cluster randomised controlled trial in Jodhpur, Rajasthan, with Accredited Social Health Activists (ASHAs) serving as the unit of randomisation. The methodology includes several key phases: a needs assessment to understand caregiver requirements, the development of the mHealth application, comprehensive training for ASHAs and a thorough evaluation of the intervention’s impact.

The effectiveness of the intervention will be measured through quantitative assessments of stress reduction, depressive symptoms and quality of life improvements, alongside qualitative insights from stakeholders. Additionally, usability and cost analyses will be conducted to evaluate the practicality and economic feasibility of the intervention.

The expected outcomes of this study include the creation of a scalable mHealth platform that facilitates remote support, bridges geographical gaps and enhances the well-being of caregivers in India’s evolving healthcare landscape.

Ethics and dissemination

Ethical approval has been obtained from the Institutional Ethical Committee of AIIMS Jodhpur (AIIMS/IEC/2022/4245).

Trial registration number

Clinical Trials Registry: CTRI/2022/12/048320.
Cohort profile: creation of the SAIL MELD-B e-cohort (SMC) and SAIL MELD-B children and young adult e-cohort (SMYC) to investigate the lived experience of the ‘burdensomeness’ of multimorbidity
Authors: Chiovoloni Roberta , Dylag Jakub J , Alwan Nisreen A , Berrington Ann , Boniface Michael , Fair Nic , Holland Emilia , Hoyle Rebecca , Shiranirad Mozhdeh , Stannard Sebastian , Zlatev Zlatko , Owen Rhiannon K , Fraser Simon , Akbari Ashley
Published: January 2025

Purpose

We have established the SAIL MELD-B electronic cohort (e-cohort SMC) and the SAIL MELD-B children and Young adults e-cohort (SMYC) as a part of the Multidisciplinary Ecosystem to study Lifecourse Determinants and Prevention of Early-onset Burdensome Multimorbidity (MELD-B) project. Each cohort has been created to investigate and develop a deeper understanding of the lived experience of the ‘burdensomeness’ of multimorbidity by identifying new clusters of burdensomeness concepts, exploring early life risk factors of multimorbidity and modelling hypothetical prevention scenarios.

Participants

The SMC and SMYC are longitudinal e-cohorts created from routinely collected individual-level population-scale anonymised data sources available within the Secure Anonymised Information Linkage (SAIL) Databank. They include individuals with available records from linked health and demographic data sources in SAIL at any time between 1 January 2000 and 31 December 2022. The SMYC e-cohort is a subset of the SMC, including only individuals born on or after the cohort start date.

Findings to date

The SMC and SMYC cohorts include 5 180 602 (50.3% female and 49.7% male) and 896 155 (48.7% female and 51.3% male) individuals, respectively. Considering both primary and secondary care health data, the five most common long-term conditions for individuals in SMC are ‘Depression’, affecting 21.6% of the cohort, ‘Anxiety’ (21.1%), ‘Asthma’ (17.5%), ‘Hypertension’ (16.2%) and ‘Atopic Eczema’ (14.1%) and the five most common conditions for individuals in SMYC are ‘Atopic Eczema’ (21.2%), ‘Asthma’ (11.6%), ‘Anxiety’ (6.0%), ‘Deafness’ (4.6%) and ‘Depression’ (4.3%).

Future plans

The SMC and SMYC e-cohorts have been developed using a reproducible, maintainable concept curation pipeline, which allows for the cohorts to be updated dynamically over time and manages for the request and processing of further approved long-term conditions and burdensomeness concepts extraction. Best practices from the MELD-B project can be utilised across other projects, accessing similar data with population-scale data sources and trusted research environments.
Patient-centred care and quality of life and hope among Japanese patients receiving home medical care: a multicentre, cross-sectional study
Authors: Iida Hidekazu , Hayashi Shinu , Yasunaka Masakazu , Tsugihashi Yukio , Hirose Misaki , Shirahige Yutaka , Kurita Noriaki
Published: January 2025

Objectives

Patient-reported outcomes reflecting quality of life (QOL) and hope are essential targets for in-home medical care. This study examined the association between the quality of patient-centred care and both QOL and hope.

Design

Multicentre, cross-sectional study.

Setting

Twenty-nine home care clinics in the Tokyo Metropolitan Area, Nara Prefecture and Nagasaki Prefecture in Japan.

Participants

200 patients receiving home medical care.

Exposure

Patient-centredness was measured using the Japanese version of the Primary Care Assessment Tool-Short Form (JPCAT-SF).

Outcome measures

The primary outcome measures were QOL, assessed using the QOL-Home Care (QOL-HC) scale, and hope, measured using the Health-Related Hope (HR-Hope) scale. Mixed-effects linear models were applied.

Results

A higher JPCAT-SF total score was associated with a higher QOL-HC score (adjusted mean difference per 10-point increase: 0.28, 95% CI 0.16 to 0.40). Among the JPCAT-SF domains, higher scores in first contact (0.16, 95% CI 0.08 to 0.23), longitudinality (0.20, 95% CI 0.11 to 0.29), comprehensiveness (services available) (0.12, 95% CI 0.03 to 0.20), comprehensiveness (services provided) (0.08, 95% CI 0.01 to 0.15) and community orientation (0.11, 95% CI 0.02 to 0.20) were also associated with higher QOL-HC scores. Similarly, a higher JPCAT-SF total score was associated with a higher HR-Hope score (adjusted mean difference per 10-point increase: 4.8, 95% CI 2.9 to 6.7). Additionally, higher scores in individual JPCAT-SF domains were associated with higher HR-Hope scores: first contact (2.7, 95% CI 1.3 to 4.1), longitudinality (2.5, 95% CI 0.8 to 4.2), coordination (1.2, 95% CI 0.2 to 2.3), comprehensiveness (services available: 1.8, 95% CI 0.5 to 3.2; services provided: 1.3, 95% CI 0.4 to 2.3) and community orientation (1.8, 95% CI 0.5 to 3.1).

Conclusions

Higher quality patient-centred care is positively associated with enhanced QOL and hope among home medical care patients. Patient-centredness should be strengthened in daily clinical practice.
Key elements for designing effective second victim support interventions: a focus group study in European clinical settings
Authors: Mira José Joaquín , Carrillo Irene , Gil-Hernández Eva , Strametz Reinhard , Knežević Krajina Hana , Schrøder Katja , Tella Susanna , Paiva Sofia Guerra , Knežević Bojana , Panella Massimiliano , Seys Deborah , Srulovici Einav , Põlluste Kaja , Vanhaecht Kris , Sousa Paulo
Published: January 2025

Background

The second victim (SV) experience limits the performance of health and care workers and places patients at risk. Peer support is recognised as the most effective, feasible and acceptable intervention to mitigate its impact.

Objective

To define a set of success factors when designing interventions to support SVs in health and care facilities based on expertise in different European countries.

Setting

International collaboration involving countries with diverse cultures, structures and legal frameworks.

Design

Qualitative research.

Method

Focus groups involving a total of 43 participants were conducted in five countries. Prominent professionals in European peer support interventions were engaged. Analysis of common elements considered key to the success of these programmes was underscored.

Results

Critical success factors for designing effective SV support interventions included the need for an occupational health approach, the establishment of a strong organisational safety culture, immediate psychological first aid, long-term resilience building, the engagement and training of peer supporters, the provision of adequate resources and ongoing support, the importance of leadership commitment and the necessity of tailoring interventions to the specific context and needs of each institution and country considering their diverse sociocultural and legal framework. The expected benefits included ensuring optimal patient care and reducing associated costs such as staff turnover and litigation.

Conclusion

Effective SV support interventions are essential for enhancing the resilience and performance of health and care workers, ultimately improving patient safety. By implementing tailored and well-resourced interventions, healthcare institutions can mitigate the negative impact of the SV phenomenon, promoting optimal care.
Interventions to increase utilisation of advanced care planning documentation for hospitalised older adults
Authors: Walker Laura E , Liwonjo Anne , Goyal Deepi G
Published: January 2025

Objective

Understanding patients’ wishes and preferences during hospitalisation is a crucial component of care. We identified a gap related to documentation of advance directives and patient preferences for care and focused on ensuring appropriate goals of care discussions were occurring and documented. Our aim was to improve the documentation of advance care planning notes to include 80% of targeted hospitalised patients.

Patients and methods

Hospitalised patients in two community hospitals were included. We performed serial Plan-Do-Measure-Act cycles. The first intervention introduced the ‘surprise question’ during an afternoon huddle. Intervention 2 emphasised documentation of the advance care planning note. The third intervention used a structured approach led by administrators at daily multidisciplinary huddles and identified patients with an Elderly Risk Assessment score of 16 or greater as targets for advance care planning documentation.

Results

From a baseline performance under 10%, we increased to greater than 80% of patients with Elderly Risk Assessment scores of 16 or higher having documented advance care planning. We were able to sustain this performance over subsequent years.

Conclusion

A structured approach that identifies a targeted population at higher risk of mortality, and implementation of a checklist at a daily multidisciplinary huddle provided sustained improvement in advance care planning documentation. This provides the opportunity for improved patient care that is aligned with their values and preferences.
Real-world evaluation of physiotherapist-led exercise prehabilitation and rehabilitation during autologous stem cell transplantation in myeloma: a single-centre experience
Authors: Land Joanne , Luong Michael K , Longden Alasdair , Rabin Neil , Kyriakou Charalampia , Sive Jonathan , Fisher Abi , Yong Kwee , McCourt Orla
Published: January 2025

Background

There is emerging evidence for the role of exercise in optimising function, quality of life (QoL) and reducing hospital length-of-stay if commenced prior to undergoing autologous stem cell transplantation (ASCT). A local pilot study of a prehabilitation and rehabilitation intervention during ASCT for myeloma patients indicated promising results and was adapted to translate into local clinical care. The aim of this report is to describe an overview of a newly implemented physiotherapist-led exercise prehabilitation and rehabilitation service delivered as part of the myeloma ASCT pathway, and present real-world findings related to changes in function and QoL.

Methods

A service evaluation was conducted at a single-centre tertiary referral hospital for haematopoetic stem cell transplantation in the United Kingdom. A hybrid service using face-to-face clinical assessments and weekly remotely supervised group exercise, via an online video conferencing platform, in the phase between stem cell harvest and admission (prehabilitation), and from discharge to 100 days post-ASCT (rehabilitation). Functional (6 min walk and timed sit-to-stand tests) and patient-reported outcome measures (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-C30) and EuroQol EQ5D-5L were assessed at preharvest, preadmission and in the post-ASCT evaluation (day 100) clinic.

Results

Patients (n=46) with a diagnosis of multiple myeloma referred for ASCT following induction chemotherapy were assessed. Baseline assessments showed high prevalence of impaired function and lower limb strength. Improvements were evident following prehabilitation prior to admission, which were maintained post-ASCT. Changes in 6 min walk test and timed sit-to-stand were significant and beyond thresholds of clinical importance. Improvements were also seen in the domains of QoL.

Conclusions

Implementation of physiotherapist-led assessments in the myeloma clinic and group exercise delivery under remote supervision are acceptable to patients undergoing ASCT and indicate benefit in improving function and QoL.
Novel and potent MICA/B antibody is therapeutically effective inKRAS LKB1mutant lung cancer models
Authors: Kowash Ryan R , Sabnani Manoj , Gray Laura T , Deng Qing , Saleh Nusrat U A , Girard Luc , Naito Yujiro , Masahiro Kentaro , Minna John D , Gerber David E , Koyama Shohei , Liu Zhiqian Lucy , Baruah Hemanta , Akbay Esra A
Published: January 2025

Background

ConcurrentKRAS LKB1(STK11, KL) mutant non-small cell lung cancers (NSCLC) do not respond well to current immune checkpoint blockade therapies, however targeting major histocompatibility complex class I-related chain A or B (MICA/B), could pose an alternative therapeutic strategy through activation of natural killer (NK) cells.

Methods

Expression of NK cell activating ligands in NSCLC cell line and patient data were analyzed. Cell surface expression of MICA/B in NSCLC cell lines was determined through flow cytometry while ligand shedding in both patient blood and cell lines was determined through ELISA. We engineered an antibody-dependent cellular cytotoxicity (ADCC) enhanced MICA/B monoclonal antibody, AHA-1031, which prevents ligand shedding without interfering with binding to natural killer group 2D while targeting cancer cells via superior ADCC. We performed in vitro assays using ELISA and flow cytometry-based assays to confirm that our antibody potently binds to and stabilizes MICA/B expression across lung cancer and other solid tumor cell lines. Additionally, we used two KL mutant NSCLC cell lines and a KL mutant patient-derived xenograft (PDX) model to demonstrate in vivo antitumor efficacy and flow cytometry analysis for immune cell activation profiling.

Results

NSCLC cell lines exhibit high MICA/B expression and secrete soluble MICA/B in vitro. Soluble MICA/B is also detected in patient blood samples. AHA-1031 binds to the α3 domain of MICA/B, preventing shedding and targeting tumor cells to ADCC. AHA-1031 exhibits high affinity and specificity to MICA/B, preventing MICA/B shedding in tumor lines and inducing ADCC in vitro. Our antibody also effectively binds and stabilizes MICA/B expression in additional tumor types and demonstrates broad specificity. We show that in two KL mutant NSCLC xenograft models and a KL mutant PDX model, treatment with AHA-1031 monotherapy significantly inhibits tumor growth compared with vehicle-treated animals with no observable toxicity. Tumor tissues from treated mice exhibit significantly increased immune cell infiltrates and activated NK cell populations.

Conclusions

Activating NK cells through MICA/B stabilization and inducing ADCC offers an alternative and potent therapy option in KL tumors. MICA/B are shed across different tumors making this therapeutic strategy universally applicable.
Lethal clinical outcome and chemotherapy and immunotherapy resistance in patients with urothelial carcinoma with MDM2 amplification or overexpression
Authors: Jin Kaifeng , Ding Yawei , Xu Jingtong , Liu Zhaopei , Zeng Han , Su Xiaohe , Zhang Lingkai , Sun Jiaxing , Wu Yuzhen , Liu Hailong , Chang Yuan , Zhu Yu , Wang Zewei , Xu Le , Zhang Weijuan , Xu Jiejie
Published: January 2025

Background

The E3 ubiquitin ligase murine double minute 2 (MDM2) binds the p53 transcriptional activation domain and acts as a potent inhibitor ofTP53pathway, one of the three most crucial oncogenic pathways in urothelial carcinoma (UC). However, the clinical significance and impact on tumor immune contexture ofMDM2amplification in UC remain unclear.

Methods

This study analyzed 240 patients with UC with matched clinical annotations from two local cohorts (ZSHS cohort and FUSCC cohort). We assessed the correlation betweenMDM2status and clinical outcomes, therapeutic efficacy, and immunological characteristics by immunohistochemical analysis and targeted sequencing. Additionally, 2264 UC samples from five independent external cohorts, with genomic, transcriptomic, and clinical data, were used for validation.

Results

MDM2amplification (MDM2Amp) or protein overexpression (MDM2OE) was associated with inferior overall survival (ZSHS cohort, Log-rank p<0.001; FUSCC cohort, Log-rank p=0.030) and reduced response to platinum-based chemotherapy (ZSHS cohort, Log-rank p<0.001) as well as anti-PD-1/PD-L1 immunotherapy (FUSCC cohort, Log-rank p=0.016) in patients with UC, irrespective ofTP53/p53 status.MDM2amplification or overexpression was further linked to high-grade UC tumors with dedifferentiated morphology. In addition, UC withMDM2amplification or overexpression was associated with an immuno-evasive contexture characterized by lower proportion of tertiary lymphoid structure infiltration, lower abundance of CD8+T cells, IFN-γ+cells, GZMB+cells, and decreased expression of immune checkpoint molecules including programmed death-ligand 1 (PD-L1), programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4).

Conclusions

MDM2amplification or overexpression defines a lethal subset of patients with UC with inferior prognosis and resistance to both platinum-based chemotherapy and immunotherapy irrespective ofTP53/p53 status. These tumors are characterized by dedifferentiated morphology and an immunosuppressive microenvironment. Accurate assessment ofMDM2status can improve risk stratification and enable personalized genomics-guided treatment for patients with UC.
Low versus high initial oral glucocorticoid dose for lupus nephritis: a pooled analysis of randomised controlled clinical trials
Authors: Saxena Amit , Sorrento Cristina , Izmirly Peter , Sullivan Janine , Gamez-Perez Monica , Law Jammie , Belmont Howard Michael , Buyon Jill P
Published: January 2025

Objective

Traditional initial treatment regimens for lupus nephritis (LN) used oral glucocorticoids (GC) in starting doses up to 1.0 mg/kg/day prednisone equivalent with or without a preceding intravenous methylprednisolone pulse. More recent management guidelines recommend lower starting oral GC doses following intravenous pulse therapy. As there have been no large studies directly comparing patients receiving low versus high initial oral GC doses, this pooled analysis of high-quality randomised controlled trials (RCTs) aims to evaluate differences in efficacy and safety.

Methods

Published data were analysed from RCTs that assessed variable GC doses in the standard of care (SOC) treatment arms. Patients receiving starting prednisone doses up to 0.5 mg/kg/day (low dose) were compared with 1.0 mg/kg/day (high dose). Complete renal response requiring urine protein-creatinine ratio <0.5 mg/mg (CRR 0.5), CRR or partial renal response (PRR), serious adverse events (SAE) and SAE due to infections at 12 months of treatment were compared between groups.

Results

417 patients from SOC arms of five studies were exposed to low-dose initial GC after intravenous pulse, while 521 patients from four studies were treated with high-dose oral GC. In patients with low-dose oral GC, 25.2% achieved CRR 0.5 at 12 months compared with 27.2% in high-dose groups, p=0.54. CRR or PRR was attained in 48.7% low-dose vs 43.6% high-dose patients, p=0.14. SAEs and infection SAEs were less common in the low-dose GC group (19.4% vs 31.6%, p<0.001 and 9.8% vs 16.5%, p=0.012, respectively).

Conclusions

Based on pooled RCT data, there was no significant difference in 12-month renal responses between patients receiving low-dose prednisone following intravenous GC compared with those receiving initial high doses. SAEs were less frequent in patients receiving low-dose initial GC. These findings support the use of lower oral GC doses in LN treatment.
Evaluating factors impacting National Institutes of Health funding in pain medicine
Authors: Kurian Christopher , Kurian Emil , Orhurhu Vwaire , Korn Elizabeth , Salisu-Orhurhu Mariam , Mueller Ariel , Houle Timothy , Shen Shiqian
Published: January 2025

Background

While many medical specialties have established links between bibliometric indices, academic rank, leadership roles, and National Institutes of Health (NIH) funding, there exists a gap within the field of pain medicine. The purpose of our study is to examine the impact of research productivity (h-index, m-index, publications, citations), professional degrees (PhD, MPH, MBA), leadership positions (program director, division chief, chairman), and faculty demographics (gender, nationality of training) on attaining NIH grant funding among pain medicine faculty.

Methods

A complete list of 98 civilian pain medicine programs was included in the study. Between September 1, 2022, and December 30, 2022, departmental websites were accessed to accrue a list of pain medicine faculty listings. Publicly available information was used to extract research productivities, professional degrees, leadership positions, faculty demographics, and NIH grant funding. Descriptive statistics were used for analysis, with NIH funding status as the primary outcome.

Results

A total of 696 pain physicians within the academic community were identified. Markers of research productivity such as a higher h- or m-index, larger number of publications and citations, PhD status, and being senior faculty (full professor, division chief, or chairman) were independently associated with NIH funding. There was no statistical difference (p>0.05) among males and females in the number of R grants received.

Conclusions

We have identified many factors associated with NIH funding status and failed to find significant gender disparities in NIH funding. These findings allow for chronic pain programs to have another set of tools to attract, promote, and retain faculty.
Sleep quality and coping styles among nurses working in tertiary cancer institutions: a mixed-method study
Authors: Pai Shubha , Suvvari Praneeth , Kodisharapu Praveen Kumar , Rayani Basanth Kumar , Palat Gayatri
Published: January 2025

Introduction

Providing nursing care is a challenging job which may lead to serious effects on sleep quality, thereby leading to lower work productivity and reduced job satisfaction. Therefore, it becomes increasingly important to adopt effective and adaptive coping strategies to deal with day-to-day stress and to improve sleep.

Aim

This study aimed to assess the sleep quality of nurses and the coping styles employed by them to deal with the stressors at the workplace.

Methods

This cross-sectional study included (n=125) nurses working across different wards and intensive care units in two cancer hospitals. The sleep quality was assessed using the Pittsburgh Sleep Quality Index, while brief COPE was used to assess the coping styles. Stress was assessed using a Likert scale.

Results

The results indicated that the majority of the nurses (59.2%) had poor sleep quality. However, most nurses employed problem-focused coping (70.4%) compared with emotion-focused (21.6%) and avoidant coping (8%). Poor sleep quality was found to have significant association with problem-focused coping (r=0.27), emotion-focused coping (r=0.25) and stress (r=0.42). A thematic analysis of the responses resulted in the emergence of eight major themes causing stress including management issues, novelty of job, family stress, health, work-life balance, workload, interpersonal relations and career growth.

Conclusion

Poor sleep quality was observed in more than half of the nurses who participated in this study. This can be attributed to several reasons mostly relating to work stress. Thus, it becomes increasingly important to address these issues and provide adequate support on an organisational level to improve their psychological well-being.
Dual antiplatelet therapy with ticagrelor vs clopidogrel in patients with TIA or minor stroke with or without symptomatic carotid artery stenosis: a post hoc analysis of the CHANCE-2 trial
Authors: Xie Xuewei , Jing Jing , Wang Anxin , Xu Qin , Zhao Xingquan , Lin Jinxi , Chen Pan , Jiang Yong , Wang Yilong , Li Hao , Meng Xia , Wang Yongjun
Published: January 2025

Background and purpose

Symptomatic internal carotid artery stenosis (sCAS) is an essential cause of transient ischaemic attack (TIA) or minor stroke. We aimed to evaluate whether the superiority of aspirin-ticagrelor over aspirin-clopidogrel varies between patients with sCAS or not.

Methods

This was a post-hoc analysis of the High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II (CHANCE-2) trial, all of which wereCYP2C19loss-of-function alleles carriers. The primary exposures of interest were the treatment group and sCAS status. The primary efficacy endpoint was the new stroke assessed within 90 days.

Results

A total of 5920 (92.3%) from 6412 were analysed, including 197 (3.3%) with sCAS and 5723 (96.7%) without sCAS. Stroke recurrence occurred in 13 (12.15%) and 11 (12.22%) patients with sCAS who received aspirin-ticagrelor and aspirin-clopidogrel, respectively (adjusted HR, 1.04; 95% CI, 0.46 to 2.36; p=0.930). Among patients without sCAS, there were 158 cases (5.52%) of new strokes in the aspirin-ticagrelor group and 222 cases (7.76%) in the aspirin-clopidogrel group (HR, 0.70; 95% CI, 0.57 to 0.86; p=0.0006). The treatment-by-sCAS subtype was not significant (p=0.405).

Conclusions

Genotype-guided dual antiplatelet treatment with aspirin-ticagrelor may be beneficial for preventing recurrent strokes in patients without sCAS; however, it appears less effective in those with sCAS. No significant interaction was found between the treatment and sCAS subtypes.

Trial registration number

NCT04078737.
Tobacco-free generation: reflecting on progress globally and its potential feasibility in India
Authors: Gupta Rakesh , Goel Sonu , Bostic Chris , Bhatt Garima , Gurung Deepak , Cyril Alexander , Gill Opinderpreet K , Prabhakara Prabhakara , Singh Rana J , Hefler Marita
Published: January 2025

Tobacco-free generation (TFG) policies, also conceptualised as smoke-free or nicotine-free generation in some geographies, envision the elimination of tobacco use initiation by preventing tobacco sales to generations born after a specified birth date. This cohort-based policy approach eventually aims to phase out tobacco use. This paper defines TFG, reviews its international developments and explores the feasibility of the TFG policy approach in India, considering the country’s federal governance structure with health as a state responsibility, within a national policy framework. Our review suggests that the concept of TFG aligns well with existing tobacco control measures in India, such as the Cigarette and Other Tobacco Products Act (COTPA), the National Tobacco Control Programme, Tobacco-free Educational Institutes and innovations such as tobacco vendor licensing and various tobacco-free campaigns. Amending section 6(a) of COTPA to replace the current prohibition of sale to and by those below 18 years of age with a specific section on TFG would be an effective approach to ensure policy coherence. Supporting grassroots movements countrywide at the state and/or substate level may activate the process within the Ministry of Health and Family Welfare, Government of India to table this proposal as an amendment in Section 6 of COTPA for the Parliament to adopt.
Repository for extended dark matter object constraints
Authors: Croon Djuna , Sevillano Muñoz Sergio
Published: January 2025

Extended dark matter objects (EDOs) are popular dark matter candidates that interact gravitationally with the Standard Model. These gravitational interactions can be used to constrain their allowed parameter space. However, EDOs can have different formation mechanisms, sizes, and shapes, requiring a case-by-case analysis when studying their impact on different areas of cosmology. We thus present a repository of all available bounds for these objects, with a code that allows plotting user-defined combinations of all up-to-date bounds for a given shape and different radii. We propose a standard for the EDOs’ mass profiles so that different sets of bounds are consistent with each other, and provide instructions on using the code and contributing to the repository.
Quantum technology master’s: a shortcut to the quantum industry?
Authors: Goorney Simon , Muñoz Borja , Sherson Jacob
Published: January 2025

In this article, we investigate a growing trend in the worldwide Quantum Technology (QT) education landscape, that of the development of master’s programs, intended to provide graduates with the knowledge and skills to take a job in the quantum industry, while serving a much shorter timeline than a doctoral degree. Through a global survey, we identified 86 master’s programs, with substantial growth since 2021. Over time master’s have become increasingly interdisciplinary, organised by multiple faculties or through joint degree programs, and offer more hands-on experiences such as internships in companies. Information from program organisers and websites suggests that the intended career destinations of their graduates are a diverse range of industries, and therefore master’s programs may be a boon to the industrialisation of quantum technologies. Finally, we identify a range of national efforts to grow the quantum workforce of many countries, “quantum program enhancements”, which augment the content of existing study programs with quantum content. This may further contribute to the growth and viability of master’s programs as a route to the quantum industry.
Formation of an Anthropogenic Rock: Mechanisms and Microstructures of Lithification of a Legacy Deposit of Cementitious Material
Authors: MacDonald John M. , Taylor George , Lewis Euan R. , Wilson Claire , Spruzeniece Liene , Slaymark Charlotte , Brown David J. , Owen Amanda
Published: January 2025

Billions of tonnes of anthropogenic geomaterials, such as slags, ashes and cementitious materials, are deposited on the Earth's surface globally every year. These materials have the potential to become rock but little is known about how they may become lithified. In this study, we document lithification of a legacy deposit of cementitious material at a former cement works in Scotland, and uncover the mechanisms and drivers for its conversion from a loose granular sediment to an anthropogenic rock. Optical and electron microscopy and chemical mapping, coupled with X-Ray Diffraction, indicate the presence of particles of waste cementitious material interpreted to be calcium-silicate-hydrate (C-S-H) formed through hydration of cement clinker; these particles are rimmed by a secondary calcite mineral cement which binds the C-S-H particles together. Partial dissolution of C-S-H followed by diffusion of Ca and OH
-
into porewaters promoted ingassing and hydroxylation of atmospheric CO
2
(fingerprinted by carbon isotope analysis). The CO
2
reacted with the dissolved Ca to precipitate the calcite cement rimming the C-S-H grains. This calcite mineral cement has therefore bonded the grains to create an anthropogenic rock. This process can potentially create benefits in terms of ground stabilisation and atmospheric CO
2
sequestration.