bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of social vulnerability and depression incidence post intracerebral haemorrhage: a cohort study
Authors: Popescu Dominique Lynn , Abramson Jessica , Keins Sophia , Mallick Akashleena , Kourkoulis Christina , Anderson Christopher D , Rosand Jonathan , Biffi Alessandro , Yechoor Nirupama 
Published: December 2024

ObjectivesSurvivors of intracerebral haemorrhage (ICH) are at high risk of incident depression, which is modified by social determinants of health (SDOH) and associated with worse functional outcomes. We sought to determine the role of prestroke SDOH in depression incidence after ICH to better characterise post-ICH outcomes.Study designWe analysed data from a cohort study of ICH survivors without prestroke depression, presenting at Massachusetts General Hospital between 2006 and 2017. We collected information from electronic health records (EHR), follow-up interviews and CT/MRI. The relationship between social vulnerability, air quality and post-ICH depression incidence within 12 months of acute haemorrhage was investigated using logistic regression models that also included EHR and CT/MRI information as predictors.ResultsParticipants were 576 survivors, median age of 72 (IQR=61–81), 317 (55%) self-reported as male and 482 (84%) as white. 204 (35%) were diagnosed with depression within 12 months of ICH. Hospital admission longer than 1 week (OR 1.80, 95% CI 1.08 to 3.00), cerebral amyloid angiopathy (CAA) burden (OR 1.45, 95% CI 1.25 to 1.68) and social vulnerability (OR 3.03, 95% CI 1.49 to 6.19) were associated with depression incidence post-ICH.ConclusionsIn addition to CAA burden and patient location 1-week post-ICH, social vulnerability was independently associated with depression among ICH survivors. Our findings suggest that social vulnerability influences ICH outcomes. Future studies should investigate how poststroke clinical care interventions can address SDOH effects to reduce incident depression and improve outcomes among ICH survivors.
An updated systematic review and meta-analysis exploring the efficacy and safety of dimethyl fumarate (DMF) for patients with multiple sclerosis (MS)
Authors: Ali Hossam Tharwat , Yousef Amr Mahmoud , El-Farargy Sara Hosny , Abdelmonhem Ahmed Mohamed , Abouda Dalia Atef , Mahmoud Ahmed Mamdoh , Elsayed Ammar Arafat , Hassaan Hazem Khaled , Afifi Ahmed M. 
Published: December 2024

BackgroundDimethyl fumarate (DMF) is increasingly used in treating multiple sclerosis (MS) with controversial results of the safety and efficacy of different DMF doses. We aimed to systematically review the literature to examine the safety and efficacy of DMF for MS patients.MethodsWe searched PubMed Medline, Cochrane, Web of Science, Scopus databases and clinicaltrials.gov up to June 2023 for the published trials evaluating the use of DMF for MS in adults. All included studies were screened and abstracted independently by two authors. Efficacy and safety outcome measures were extracted. The meta-analysis was conducted using Review Manager 5.4.Results10 studies including eight randomised controlled trials, one open-label and one single-arm before-after study with a total population size of 4278 patients were included. DMF group showed a statistically significant reduction in the proportion of relapses compared with the control group, (OR: 0.47, 95% CI: [0.41, 0.55], p<0.00001) with no statistical differences between 240 mg two times per day and three times a day doses. Furthermore, the DMF group had a significant reduction in Gd-enhanced lesions compared with control (MD=−1.53, 95% CI: [−1.91 to –1.41], p<0.00001). Our results showed a non-significant difference in adverse events that led to discontinuation of the study with an OR of 1.29 (95% CI: [0.98, 1.71], p value=0.07).DiscussionDMF had significant efficacy and safety compared with the control, with no difference between the DMF doses. More studies with large sample sizes and longer follow-ups are needed to detect long-term safety and efficacy.
Sintilimab plus bevacizumab followed by resection in intermediate-stage hepatocellular carcinoma: a phase Ib clinical trial with biomarker analysis
Authors: Sun Hui-Chuan , Zhu Xiao-Dong , Wang Zi-Yi , Gao Qiang , Ji Yuan , Shi Ying-Hong , Wang Xiao-Ying , Qiu Shuang-Jian , Huang Cheng , Shen Ying-Hao , Zhou Jian , Fan Jia 
Published: December 2024

ObjectiveThis phase Ib trial aimed to assess the safety and efficacy of sintilimab plus bevacizumab (sintilimab/bev), followed by resection in patients with potentially resectable intermediate-stage hepatocellular carcinoma (HCC) and explore the clinical implications of circulating tumour DNA (ctDNA) and T cell receptor (TCR) repertoire.Methods and analysisEligible patients with intermediate-stage HCC received sintilimab/bev treatment. Patients with partial response or stable disease for at least two consecutive evaluations and technically resectable received hepatectomy. Postoperatively patients continued to receive sintilimab/bev until tumour recurrence or intolerable toxicities for up to 12 months. The primary endpoints were treatment safety and event-free survival (EFS). Plasma ctDNA measurements and TCR repertoire were analysed.Results30 patients were enrolled. 17 (56.7%) patients received liver resection. Grade 3 treatment-related adverse events occurred in seven patients (23.3%). No grade 4/5 AE or postoperative mortality was observed. The median EFS of the 30 patients was 16.3 months (95% CI 13.4 to 19.2). The 12-month and 24-month survival rates were 93.2% and 82.0%, respectively. Of the 17 patients who received hepatectomy, the median recurrence-free survival was 14.1 months (95% CI 8.9 to 19.4). A lower ctDNA measurement and higher TCR repertoire were associated with better tumour response or patients’ survival.ConclusionsThe study suggested systemic therapy with sintilimab/bev was safe and effective in patients with intermediate-stage HCC, and resection in selected patients was associated with improved survival. ctDNA measurement and TCR repertoire may help identify patients who may benefit from sintilimab/bev treatment and patients with a higher risk of tumour recurrence.Trial registration numberNCT04843943.
Use of metered dose inhalers for bronchodilator responsiveness testing: laboratory practices in Australia and opportunities for carbon footprint reduction
Authors: Loftus Michael J , Roberts Jayne , Romeo Nicholas , Matsas Pam , Leder Karin , Borg Brigitte , Miller Belinda R 
Published: December 2024

BackgroundMetered dose inhalers (MDIs) are important devices for delivering inhaled medications; however, they have an outsized carbon footprint due to their propellant gas. Many short-acting beta-agonist inhalers contain HFA-134a which has a global warming potential >1000 fold higher than carbon dioxide. We aimed to determine the practices around MDI use and disposal within Australia’s major lung function testing laboratories and identify the actions that most influence the carbon footprint of bronchodilator responsiveness (BDR) testing.MethodsAustralia’s 45 accredited lung function laboratories were invited to participate in an online survey asking about their volume of BDR testing, as well as practices around MDI use such as the number of actuations per BDR test, reuse of MDIs between patients and disposal method. We calculated MDI-associated carbon dioxide equivalent (CO2e) emissions by combining previously published estimates.Results39 laboratories completed the survey. Most laboratories used 4 actuations of salbutamol per BDR test for both adults (27/34, 79.4%) and children (17/20, 85%), but this ranged from 2 to 12. Only three (7.7%) laboratories did not routinely reuse MDIs between patients; however, they all sent their used MDIs for high-temperature incineration. Based on different combinations of observed MDI practices in Australia, we identified a potential sixfold difference in CO2e per 100 BDR tests, from as low as 23.3 kg CO2e up to 166 kg CO2e.ConclusionsWe identified three key practices to reduce the carbon footprint of BDR testing: disposing of MDIs via high-temperature incineration, reducing the number of actuations per BDR test and reusing MDIs between patients.
Lung function may recover after coal mine fire smoke exposure: a longitudinal cohort study
Authors: Holt Nicolette R , Smith Catherine L , Gao Caroline X , Borg Brigitte , Lane Tyler , Brown David , Ikin Jillian , Makar Annie , McCrabb Thomas , Thomas Mikayla , Nilsen Kris , Thompson Bruce R , Abramson Michael J 
Published: December 2024

Background and objectiveThe 2014 Hazelwood coal mine fire exposed residents in nearby Morwell to high concentrations of particulate matter <2.5 µm (PM2.5) for approximately 6 weeks. This analysis aimed to evaluate the long-term impact on respiratory health.MethodsAdults from Morwell and the unexposed town of Sale completed validated respiratory questionnaires and performed spirometry, gas transfer and oscillometry 3.5–4 years (round 1) and 7.3–7.8 years (round 2) after the fire. Individual PM2.5exposure levels were estimated using chemical transport models mapped onto participant-reported time-location data. Mixed-effects regression models were fitted to analyse associations between PM2.5exposure and outcomes, controlling for key confounders.ResultsFrom 519 (346 exposed) round 1 participants, 329 (217 exposed) participated in round 2. Spirometry and gas transfer in round 2 were mostly lower compared with round 1, excepting forced vital capacity (FVC) (increased) and forced expiratory volume in 1 second (minimal change). The effect of mine fire-related PM2.5exposure changed from a negative effect in round 1 to no effect in round 2 for both pre-bronchodilator (p=0.005) and post-bronchodilator FVC (p=0.032). PM2.5was not associated with gas transfer in either round. For post-bronchodilator reactance and area under the curve, a negative impact of PM2.5in round 1 showed signs of recovery in round 2 (both p<0.001).ConclusionIn this novel study evaluating long-term respiratory outcomes after medium-duration high concentration PM2.5exposure, the attenuated associations between exposure and respiratory function may indicate some recovery in lung function. With increased frequency and severity of landscape fires observed globally, these results inform public health policies and planning.
What is the true target population for biologics in real-life COPD or asthma-COPD overlap patients?
Authors: Zysman Maéva , Herman Fanchon , Grassion Léo , Taillé Camille , Gonzalez-Bermejo Jesus , Guecamburu Marina , Roche Nicolas , Pavot Arthur , Girodet Pierre-Olivier , Bourdin Arnaud , Molinari Nicolas , Berger Patrick 
Published: December 2024

IntroductionBiologics provide significant benefits in asthma, reducing exacerbations and symptoms. Some biologics have shown promising results in small subgroups of patients with chronic obstructive pulmonary disease (COPD) and frequent exacerbations. Nevertheless, real-life data on the size of the COPD target population remain scarce.MethodsWe analysed the characteristics of COPD and coexisting asthma and COPD patients included in the prospective multicentre, French COhort of BRonchial obstruction and Asthma, between 2008 and 2023 and evaluated the number of patients who could correspond to the inclusion criteria of randomised controlled trials evaluating various biologics targeting interleukin 33 (IL-33) (-receptor), IL-5 (-receptor), IL-4Rα or TSLP, in routine clinical practice.ResultsAmong 434 COPD patients, only 21.7% met inclusion criteria for at least one biologic. Among patients with asthma, 54 (3.5%) had coexisting features of COPD in terms of age, smoking status and airflow obstruction and met inclusion criteria for at least one biologic. Notably, these patients were predominantly female, with worse lung function. Globally, the target chronic airway diseases population of the eagerly awaited biologics remains limited to a small part (ie, 1.3%–8%, depending on the biologic).ConclusionIn a real-life COPD and asthma population (including asthmatic patients with features of COPD), the proportion of patients satisfying selection criteria applied in randomised controlled trials assessing the efficacy of biologics remains limited to less than 10% of the whole population.
Expectations and experiences of pain during medical abortion at home: a secondary, mixed-methods analysis of a patient survey in England and Wales
Authors: McCulloch Hannah , Perro Danielle , Taghinejadi Neda , Whitehouse Katherine C , Lohr Patricia A 
Published: December 2024

ObjectiveTo explore experiences of pain during medical abortion and provide patient-centred recommendations for improving abortion experience and pain counselling.MethodsWe invited patients of British Pregnancy Advisory Service who underwent medical abortion up to 10 weeks’ gestation to participate in an online, English language questionnaire from November 2021 to March 2022. Participants answered questions about pain, method preference, abortion experience, advice, and how they would describe pain experienced to a friend. In this secondary analysis, we analysed free-text responses using reflexive thematic analysis techniques. We used descriptive statistics and parametric tests to analyse quantitative responses.ResultsOf 11 906 patients invited to participate, 1596 (13.4%) completed the questionnaire, including at least one free-text comment. Participants used a range of descriptors for medical abortion pain across three broad themes: pain severity, pain quality and comparisons to other reproductive pain. Some found the commonly used analogy to period pain misleading. Many felt unprepared for the level of pain they experienced, which they attributed to provider comparisons to period pain, as well as a lack of detailed, realistic anticipatory pain counselling. Qualitative and quantitative results suggest pain experiences impact method preference. Participants recommended better counselling for pain and abortion preparation, including first-hand accounts of medical abortion at home and a wide and accessible range of descriptions of pain.ConclusionsAbortion providers should use patient-centred recommendations to better prepare patients for pain during medical abortion. Setting realistic expectations can improve abortion experience and support informed method choice. Further research is needed to develop and test patient-centred counselling materials.
Nebulised high-dose corticosteroids as add-on therapy for adults with asthma exacerbation: a randomised controlled trial
Authors: Kornthatchapong Kumpol , Chatchairatanavej Nat , Chormai Nattaya , Srivilaithon Winchana , Limjindaporn Chitlada , Saiphoklang Narongkorn , Sri-on Jiraporn 
Published: December 2024

BackgroundEvidence regarding high-dose inhaled corticosteroids (HDICS) in asthma exacerbations in adults is insufficient. This study compares the treatment outcomes of HDICS as add-on therapy to the outcomes of standard treatment in adult patients with acute asthma exacerbation in the ED.MethodsThis was a single-centre, triple-blind, randomised controlled trial conducted in the ED in Thailand between March 2022 and April 2023. Adult patients with asthma exacerbation were randomly assigned to receive either a placebo (normal saline) or HDICS (budesonide 9000 µg) nebulisation combined with beta agonist and ipratropium within the first hour. The primary endpoints were length of ED stay, hospital admission and ED revisit. The secondary endpoints were dyspnoea scale, pulmonary functions, length of hospital stay and home exacerbation after ED discharge.ResultsA total of 88 patients were randomly assigned to one of two groups: 44 patients received a HDICS and 44 patients were placed in the control group. The HDICS group had a significantly shorter ED length of stay (adjusted mean difference −133.6 min; 95% CI −242.4 to −24.8 min; p=0.016), and a higher proportion of ED discharged home within 8 and 16 hours compared with the control group. However, there were no significant differences between the two groups in hospital admission rates, ED revisit, dyspnoea scale, pulmonary functions, length of hospital stay or home exacerbation after ED discharge.ConclusionsHDICS may be useful as an add-on therapy to standard treatment for asthma exacerbation in adults to reduce ED stay.Trial registration numberTCTR20201214001.
Age of menopause, healthy lifestyle and cardiovascular disease in women: a prospective cohort study
Authors: Pant Anushriya , Gibson Alice A , Marschner Simone , Liao Lee P , Laranjo Liliana , Chow Clara K , Zaman Sarah 
Published: December 2024

BackgroundMenopause is a timely opportunity to screen for cardiovascular disease (CVD) and intervene with healthier lifestyles. We investigated the association between premature/early menopause and the likelihood of CVD and whether a healthy lifestyle is associated with a lower likelihood of CVD in menopausal woman.MethodsThe Sax Institute’s 45 and Up Study prospectively recruited participants aged ≥45 years (n=267 357) between 2005 and 2009 (New South Wales, Australia). Our study included women without prior CVD and reporting menopausal age at baseline. Primary outcome was new-onset CVD (self-reported heart disease/stroke) based on survey data at Wave 2 (2012–2015) and/or Wave 3 (2018–2020). Logistic regression models assessed the associations of premature (age <40 years) and early (age 40–44 years) menopause with CVD, compared with menopause between 50 and 52 years, adjusting for sociodemographic and clinical variables. Healthy lifestyle adherence was assessed using a score of five factors: smoking, physical activity, sitting, sleep and diet.ResultsWe included 46 238 women (mean age 62.1±8.2 years), with 5416 (11.7%) cases of CVD over 15-year follow-up. After adjustment, the odds of CVD was higher in women with premature menopause (OR 1.36, 95% CIs 1.17 to 1.59; p<0.0001) and early menopause (OR 1.15, 95% CI 1.03 to 1.28; p=0.013) compared with menopause between 50 and 52 years. Among all women, high (score 9–10) versus low (score 0–5) healthy lifestyle adherence led to 23% lower odds of CVD (OR 0.77, 95% CI 0.68 to 0.86; p<0.0001), and in women with premature menopause, led to 52% lower odds of CVD (OR 0.48, 95% CI 0.30 to 0.77, p=0.0022). Lifestyle effect did not significantly differ between menopause categories (interaction, p=0.71).ConclusionWomen with premature/early menopause are at higher likelihood for CVD. Lifestyle modification is associated with consistent reduction of the likelihood of CVD in women and should be encouraged across the life course.
Preclinical development of three novel CARs targeting CD79b for the treatment of non-Hodgkin’s lymphoma and characterization of the loss of the target antigen
Authors: Esquinas Esperanza , Moreno-Sanz Alvaro , Sandá Victor , Stodulski-Ciesla Damian , Borregón Jennifer , Peña-Blanque Virginia , Fernández-Calles Javier , Fernandez-Fuentes Narcis , Serrano-Lopez Juana , Juan Manel , Engel Pablo , Llamas-Sillero Pilar , Solán-Blanco Laura , Martin-Antonio Beatriz 
Published: December 2024

BackgroundInfusion of T cells modified with a chimeric antigen receptor (CAR) targeting CD19 has achieved exceptional responses in patients with non-Hodgkin’s lymphoma (NHL), which led to the approval of CAR targeting CD19 (CART19) (Axi-cel and Liso-cel) as second line of treatment for adult patients with relapsed/refractory NHL. Unfortunately, 60% of patients still relapse after CART19 due to either a loss of expression of the target antigen (CD19) in the tumor cell, observed in 27% of relapsed patients, a limited CAR-T persistence, and additional mechanisms, including the suppression of the tumor microenvironment. Clinic strategies to prevent target antigen loss include sequential treatment with CARs directed at CD20 or CD22, which have caused loss of the second antigen, suggesting targeting other antigens less prone to disappear. CD79b, expressed in NHL, is a target in patients treated with antibody-drug conjugates (ADC). However, the limited efficacy of ADC suggests that a CAR therapy targeting CD79b might improve results.MethodsWe designed three new CARs against CD79b termed CAR for Lymphoma (CARLY)1, 2 and 3. We compared their efficacy, phenotype, and inflammatory profiles with CART19 (ARI0001) and CARTBCMA (ARI0002h), which can treat NHL. We also analyzed the target antigen’s expression loss (CD79b, CD19, and B-cell maturation antigen(BCMA)).ResultsWe found that CARLY2 and CARLY3 had high affinity and specificity towards CD79b on B cells. In vitro, all CAR-T cells had similar anti-NHL efficacy, which was retained in an NHL model of CD19−relapse. In vivo, CARLY3 showed the highest efficacy. Analysis of the loss of the target antigen demonstrated that CARLY cells induced CD79b and CD19 downregulation on NHL cells with concomitant trogocytosis of these antigens to T cells, being most notorious in CARLY2, which had the highest affinity towards CD79b and CD19, and supporting the selection of CARLY3 to design a new treatment for patients with NHL. Finally, we created a CAR treatment based on dual targeting of CD79b and BCMA to avoid losing the target antigen. This treatment showed the highest efficacy and did not cause loss of the target antigen.ConclusionsBased on specificity, efficacy, and loss of the target antigen, CARLY3 represents a potential novel CAR treatment for NHL.
Edges of perception: balancing sensory loss and potential in assistive technology
Authors: Krijger Femke 
Published: December 2024

Being deafblind means my perception differs profoundly from those who are conventionally sighted and have non-impaired hearing. A lot of hidden knowledge is to be found in the disparity between these differing experiences that could be of great value in developing assistive technologies that have a broad scope to engage with both disabled and non-disabled users. This article explores the balancing act between sensory loss and the potential inherent in all of us and how this should be part of the design process of haptic assistive technology.Facing the true impact of my sensory loss, I realised it held the unexpected gift of a—literally—different perspective. I am losing sights and sounds, but the world still reveals itself to me in many ways. Exploring my sensory potential, I combine daily life experiences and theoretical knowledge to better understand how to get the most out of my sensory processing systems. The goal is not to compensate what is lost, but stay connected in a way that enables me to live my life to the fullest.I undertake sensory life hacks based on the brain’s unmatched capacity to adjust to circumstances and work withanykind of input. Both predicting processing and neuroplasticity offer an operating system of highly evolved flexibility that allows and even encourages creative solutions. I adjust my coping strategies to align them with these processes shaping my perceptual experience, balancing sensory loss and sensory gain.I believe there is great potential to enrich daily life experiences with haptic assistive technology, building on the natural sensory abilities we have as human beings, co-creating life. However, this comes with challenges: researchers who are not sensorily impaired should consider through experience that we all have limited perception in a way. At the edges of the familiar, you have to face your perceptual limits, pushing you out of your comfort zone and in doing so space is being created for growth; researchers used to the dominance of sight and hearing are less used to consciously experiencing the power of sensory proximity, such as touch and proprioception. These bodily tactile senses, however, are grounding senses in all of us and display a broad scope of sensations to be experienced.The hereditary disease that causes deafblindness forced me to explore the edges of my perception, and instead of devastating loss I discovered a richness of sensory abilities. This article is a plea to dive into this, using my lived experience and critical knowledge. Realising this potential can mean that inclusive research on assistive technologies might really do what it promises, co-creating technologies to enhance life experiences.