tbuckley/cabot-search huggingface dataset:
Effects and costs of a multi-component menstrual health intervention (MENISCUS) on mental health problems, educational performance, and menstrual health in Ugandan secondary schools: an open-label, school-based, cluster-randomised controlled trial
Authors: Kate A Nelson, Stephen Lagony, Catherine Kansiime, Belen Torondel, Clare Tanton, Denis Ndekezi, Levicatus Mugenyi, Ratifah Batuusa, Christopher Baleke, Katherine A Thomas, Titus Ssesanga, Robert Bakanoma, Prossy Namirembe, Aggrey Tumuhimbise, Beatrice Nanyonga, Rodah Nambi, Edward Obicho, Denis Ssenyondwa, Daria Bucci, Sophie Belfield, Agnes Akech Ocen, Shamirah Nakalema, Connie Alezuyo, Fred Matovu, Stella Neema, Nambusi Kyegombe, Giulia Greco, John Jerrim, Chris Bonell, Janet A Seeley, Helen A Weiss
Journal: The Lancet Global Health (2025)
Personalised risk-prediction tools for cryptococcal meningitis mortality to guide treatment stratification in sub-Saharan Africa: a prognostic modelling study based on pooled analysis of two randomised controlled trials
Authors: Thomas H A Samuels, Sile F Molloy, David S Lawrence, Angela Loyse, Cecilia Kanyama, Robert S Heyderman, Wai Shing Lai, Sayoki Mfinanga, Sokoine Lesikari, Duncan Chanda, Charles Kouanfack, Elvis Temfack, Olivier Lortholary, Mina C Hosseinipour, Adrienne K Chan, David B Meya, David R Boulware, Henry C Mwandumba, Graeme Meintjes, Conrad Muzoora, Mosepele Mosepele, Chiratidzo E Ndhlovu, Nabila Youssouf, Thomas S Harrison, Joseph N Jarvis, Rishi K Gupta
Journal: The Lancet Global Health (2025)
HIV prevention and undiagnosed infections in children in sub-Saharan Africa
Authors: Souleymane Tassembedo, Nicolas Meda, Chipepo Kankasa, Roger Shapiro, Theodore Ruel, Ameena Goga, Mwiya Mwiya, Isidore Tiandiogo Traore, Thorkild Tylleskär, Anais Mennecier, Jean Pierre Moles, Philippe Van de Perre, Nicolas Nagot
Journal: The Lancet HIV (2025)
Physiologically based serum ferritin thresholds for iron deficiency among women and children from Africa, Asia, Europe, and central America: a multinational comparative study
Authors: O Yaw Addo, Zuguo Mei, Maria Elena D Jefferds, Mica Jenkins, Rafael Flores-Ayala, Anne M Williams, Melissa Fox Young, Hanqi Luo, Yi-An Ko, Ioannis Papassotiriou, Mireya Palmieri, Karla Mesarina, Zulfiqar Bhutta, Parminder S Suchdev, Gary M Brittenham
Journal: The Lancet Global Health (2025)
Infant-level and child-level predictors of mortality in low-resource settings: the WHO Child Mortality Risk Stratification Multi-Country Pooled Cohort
Authors: Tahmeed Ahmed, Waseem Ali, Alemayehu Argaw, Rajiv Bahl, Jeanette Bailey, Abdullah Baqui, Elodie Becquey, James A. Berkley, Kenneth Brown, Mohammed Jobayer Chisti, Ranadip Chowdhury, Hama A. Diallo, Christopher Duggan, Denise Evans, Wafaie Fawzi, Ameena Goga, Rebecca Grais, Ousmane Guindo, David Hamer, Sonja Hess, Lieven Huybregts, Sheila Isanaka, Fyezah Jeha, Jerome Kabakyenga, Patrick Kabore, Siri Kaldenbach, Marko Kerac, Md. Alfazal Khan, Rasheda Khanam, Niranjan Kissoon, Sengchanh Kounnavong, Carl Lachat, Lacey LaGrone, Agnes Le Port, Natasha Lelijveld, Jef Leroy, Mustafa Mahfuz, Mark Manary, Karim P. Manji, Sam Marconi, Marie McGrath, Venkata Raghava Mohan, Sophie Moore, Nathan Kenya Mugisha, Ezekiel Mupere, Shalton Mwaringa, Sindhu Kulandaipalayam Natarajan, Moses Ngari, Imran Nisar, Yasir Bin Nisar, Deanna Olney, Jean-Bosco Ouedraogo, Andrew Prentice, Audrey Prost, Dominique Roberfroid, Peter Rocker, Nigel Rollins, Marie Ruel, Ali Saleem, Sunil Sazawal, Catherine Schwinger, Benson Singa, Heather Stobaugh, Tor A. Strand, Molly Timbwa, Laéticia Céline Toe, Indi Trehan, Geeta Trilok-Kumar, Wieger Voskuijl, Judd L. Walson, Dongqing Wang, Matthew Wiens, None Ayushi
Journal: The Lancet Global Health (2025)
Apolipoprotein E in Alzheimer’s disease: molecular insights and therapeutic opportunities
Authors: Abdel Ali Belaidi, Ashley I Bush, Scott Ayton
Journal: Molecular Neurodegeneration (2025)

Abstract Apolipoprotein E ( APOE- gene; apoE- protein) is the strongest genetic modulator of late-onset Alzheimer’s disease (AD), with its three major isoforms conferring risk for disease ε2 &lt; ε3 &lt; ε4. Emerging protective gene variants, such as APOE Christchurch and the COLBOS variant of REELIN , an alternative target of certain apoE receptors, offer novel insights into resilience against AD. In recent years, the role of apoE has been shown to extend beyond its primary function in lipid transport, influencing multiple biological processes, including amyloid-β (Aβ) aggregation, tau pathology, neuroinflammation, autophagy, cerebrovascular integrity and protection from lipid peroxidation and the resulting ferroptotic cell death. While the detrimental influence of apoE ε4 on these and other processes has been well described, the molecular mechanisms underpinning this disadvantage require further enunciation, particularly to realize therapeutic opportunities related to apoE. This review explores the multifaceted roles of apoE in AD pathogenesis, emphasizing recent discoveries and translational approaches to target apoE-mediated pathways. These findings underscore the potential for apoE-based therapeutic strategies to prevent or mitigate AD in genetically at-risk populations.
Conformal prediction enables disease course prediction and allows individualized diagnostic uncertainty in multiple sclerosis
Authors: Akshai Parakkal Sreenivasan, Aina Vaivade, Yassine Noui, Payam Emami Khoonsari, Joachim Burman, Ola Spjuth, Kim Kultima
Journal: npj Digital Medicine (2025)

Abstract Accurate assessment of progression and disease course in multiple sclerosis (MS) is vital for timely and appropriate clinical intervention. The gradual transition from relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS) is often diagnosed retrospectively with a typical delay of three years. To address this diagnostic delay, we developed a predictive model that uses electronic health records to distinguish between RRMS and SPMS at each individual visit. To enable reliable predictions, conformal prediction was implemented at the individual patient level with a confidence of 93%. Our model accurately predicted the change in diagnosis from RRMS to SPMS for patients who transitioned during the study period. Additionally, we identified new patients who, with high probability, are in the transition phase but have not yet received a clinical diagnosis. Our methodology aids in monitoring MS progression and proactively identifying transitioning patients. An anonymized model is available at https://msp-tracker.serve.scilifelab.se/ .
Distinct intracellular spatiotemporal expression of Calmodulin genes underlies functional diversity of CaM-dependent signaling in cardiac myocytes
Authors: Vladimir Bogdanov, Juan I E Mariangelo, Andrew M Soltisz, Galina Sakuta, Anastasia Pokrass, Casey Beard, Benjamin Hernandez Orengo, Roman Kalinin, Ali Ulker, Bennett Yunker, Svetlana Tikunova, Jenna Thuma, Xianyao Xu, Thomas J Hund, Rengasayee Veeraraghavan, Jonathan P Davis, Sandor Györke
Journal: Cardiovascular Research (2025)

Abstract Aims This study aims to resolve the mechanisms underlying Calmodulin (CaM)'s signaling diversity by investigating whether the three CaM genes—Calm1, Calm2, and Calm3—play distinct or redundant roles in cardiac myocytes, focusing on their spatial mRNA localization and interactions with key targets. Methods and Results We utilized single-molecule mRNA detection and 3D imaging to map the spatial distribution of Calm1, Calm2, and Calm3 mRNAs within ventricular myocytes. These mRNAs were found to be consistently positioned within specific cellular zones, overlapping with their target mRNAs and forming region-specific transcript conjunctions. This spatial organization aligns with two distinct protein synthesis pathways: centralized synthesis near the nucleus for proteins such as Cx43 and localized synthesis in more peripheral cytosolic areas for proteins like RyR2. Ablation of Calm1 triggered compensatory increases in Calm2 and Calm3; however, this compensation was insufficient to restore normal CaM transcript distribution, leading to disrupted Ca²⁺ handling. In the context of hypertrophic heart failure (HF), the distribution and spatial interactions of CaM transcripts, while potentially adaptive to support myocyte growth, become disrupted, leading to disorganized CaM signaling. Conclusion Our findings reveal that Calm1, Calm2, and Calm3 fulfill distinct, non-redundant roles in cardiac myocytes through their spatially regulated mRNA localization (spatiotemporal coding). This precise spatial control of mRNA localization is critical for region-specific CaM signaling and is disrupted in hypertrophic heart failure, contributing to pathological remodeling.
Pulsed Field Ablation of Persistent Atrial Fibrillation With Continuous ECG Monitoring Follow-Up: ADVANTAGE AF-Phase 2
Authors: Vivek Y. Reddy, Edward P. Gerstenfeld, Boris Schmidt, Jason G. Andrade, Devi Nair, Andrea Natale, Walid Saliba, Philipp Sommer, Andreas Metzner, Atul Verma, Troy Hounshell, Anish Amin, Philip Gentlesk, Stanislav Weiner, Frank A. Cuoco, Jamie Kim, Mohit K. Turagam, Gery Tomassoni, Chinmay Patel, Ziad Issa, Michael Shehata, Allison M. Anderson, Thomas J. Stoltz, Jonathan D. Raybuck, Torri Schwartz, Brad S. Sutton, Moussa Mansour
Journal: Circulation (2025)

Background: There is sparse high-quality safety and effectiveness data for pulsed field ablation (PFA) of persistent atrial fibrillation (PerAF), where lesions beyond pulmonary vein isolation (PVI) are often placed. Additionally, no large trials have used insertable cardiac monitors (ICMs) for continuous rhythm monitoring post-ablation in PerAF patients, or after PFA in any AF population. In ADVANTAGE AF-Phase 2 , PerAF patients underwent PFA for PVI and posterior wall ablation (PWA), and in a sub-cohort, cavotricuspid isthmus (CTI) ablation for typical atrial flutter. Methods: PerAF pts underwent PVI and PWA with the pentaspline PFA catheter, and CTI with a novel focal-linear PFA catheter after IV NTG prophylaxis. Patients were followed for 1 year with continuous rhythm monitoring after ablation with ICMs to 1) emulate traditional intermittent monitoring for the primary efficacy endpoint, and 2) examine atrial arrhythmia (AA) burden and episode duration. Results: This 255-patient cohort (age 66.7±9.3, female 29%, CHA 2 DS 2 -VASc 2.4±1.4, BMI 30.9±5.3, left atrium diameter 4.3±0.6 cm) underwent PVI plus PWA (99.6%/100% acute success); a subpopulation (n=141; 55.3%) also received CTI PFA, with 98.6% achieving bidirectional block without complications (ST changes, ventricular fibrillation). CTI ablation took 8±13 minutes, using 18±6 PF applications and 4±2 mg IV NTG. The total procedure and atrial dwell times were 105±36 and 59±24 minutes, respectively. Mimicking traditional monitoring, freedom from AA was 73.4% with adverse events in 2.4%, both meeting prespecified endpoint criteria. Freedom from recurrent atrial flutter was 97.2%. Detailed analysis of the full ICM data revealed freedom from AA ≥30 seconds in 52.0%, and no episode exceeded 24 hours in 94.0% of this PerAF cohort. An AA burden &gt;0.1% or longest episode duration &gt;1 hour were both predictive of increased healthcare utilization. One-year procedural effectiveness was 71.6% and 70.0% using these ≤0.1% burden and &lt;1 hour duration thresholds, respectively. Conclusions: In ADVANTAGE AF-Phase 2 , the first multicenter PerAF study of PFA with continuous rhythm monitoring: i) CTI ablation with NTG prophylaxis was safe and effective, ii) PVI + PWA was safe and effective, and iii) an AA burden &lt;0.1% and AA episode &lt;1 hour duration were endpoints associated with the lowest healthcare utilization.
Exercise-induced bronchial hyperresponsiveness and parental ISAAC questionnaire responses
Authors: AL Ponsonby, D Couper, T Dwyer, A Carmichael, R Wood-Baker
Journal: European Respiratory Journal (1996)

The predictive value of parental questionnaire responses for exercise-induced bronchoconstriction in childhood asthma has not been fully clarified. The aim of this study was to compare exercise-induced bronchial hyperresponsiveness in 7 year old children with parental responses to core questions in the International Study of Asthma and Allergies in Childhood (ISAAC) study. A cross-sectional study was conducted on 191 (91% of eligible) children from seven randomly selected schools in Southern Tasmania. Study measurements included a parental questionnaire and exercise challenge testing, using a recently validated 6 min free-running protocol. The response to exercise was assessed using forced expiratory volume in one second (FEV1) measurement. The median percentage fall in FEV1 was significantly higher in children whose parents responded positively to ISAAC questions on a history of wheeze (p = 0.0031) or asthma (p = 0.0005), recent wheeze (p = 0.0005), sleep disturbance due to wheeze (p = 0.0005), or exercise-induced wheeze (p = 0.0015). Receiver operating characteristic (ROC) curve analysis showed exercise-induced bronchial hyperresponsiveness to be a good indicator of current asthma status. Using a 12% or greater fall in FEV1 postexercise as a positive test response, the exercise challenge had sensitivity and specificity estimates for current asthma and exercise-induced wheeze of (0.58 and 0.77) and (0.60 and 0.77), respectively. In conclusion, the respiratory response to exercise was consistent with parental responses to the ISAAC questionnaire in a population-based sample of 7 year old children. These findings will assist interpretation of large ISAAC studies in terms of asthma prevalence.
Effects of long-term nocturnal nasal ventilation on spontaneous breathing during sleep in neuromuscular and chest wall disorders
Authors: AJ Piper, CE Sullivan
Journal: European Respiratory Journal (1996)

Nocturnal nasal intermittent positive pressure ventilation (NIPPV) is an effective means of normalizing awake blood gases in patients with respiratory insufficiency due to neuromuscular or chest wall dysfunction. However, little attention has been paid to the effects of long-term ventilation on spontaneous breathing during sleep in such patients. The purpose of this study was to determine whether spontaneous breathing during sleep improved after long-term nasal ventilation. Fourteen patients with documented nocturnal respiratory failure, who had been treated with nocturnal NIPPV for at least 6 months, were reviewed with an all night polysomnograph on a night without ventilatory support. The severity of nocturnal desaturation both in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep without nocturnal ventilation was compared to desaturation measured during the initial diagnostic study. Spontaneous daytime blood gas values (mean +/- SD) were significantly improved at follow-up compared to values obtained prior to nasal ventilation: arterial oxygen tension (Pa,O2): 7.5 +/- 1.2 to 10.2 +/- 1.3 kPa (p &lt; 0.005); arterial carbon dioxide tension (Pa,CO2) 8.2 +/- 1.6 to 6.4 +/- 0.7 kPa (p &lt; 0.001). Significant improvements in inspiratory muscle strength were also observed with maximal inspiratory pressure (Pl, max) increasing from a baseline value of 41 +/- 18 to 65 +/- 26% predicted measured prior to the night of ventilation withdrawal (p &lt; 0.003). Spontaneous breathing during sleep after long-term treatment was markedly improved although still abnormal. During NREM sleep without ventilatory support, oxygen desaturation was significantly less severe compared to the initial study (arterial oxygen saturation (Sa,O2) 88 +/- 4 vs 78 +/- 8%; p &lt; 0.001). Minimum Sa,O2 during REM sleep similarly improved from a mean value of 49 +/- 14% during the diagnostic night to 73 +/- 10% at review follow-up (p &lt; 0.001). In 12 patients, transcutaneous carbon dioxide was measured continuously during sleep on both occasions and demonstrated significantly less CO2 retention during follow-up compared to control studies both in NREM (p &lt; 0.003) and REM sleep states (p &lt; 0.004). Long-term nocturnal ventilation produces improved respiratory drive both asleep and awake and improved arousal responses to abnormal blood gases.
Acute bronchial obstruction following inhalation of PAF in asthmatic and normal subjects: comparison with methacholine
Authors: RE Louis, MF Radermecker
Journal: European Respiratory Journal (1996)

Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma but controversies exist about bronchial responsiveness toward this mediator in asthma. We have compared the variations in the specific conductance (sGaw) and forced expiratory volume in one second (FEV1) in 12 asthmatics and 12 normal subjects after inhalation of doubling doses of PAF (15-120 micrograms) and methacholine (18 to at least 144 micrograms). In order to take into account a possible tachyphylaxis, we compared PAF dose-response curves performed on one day with the curves obtained by giving the same doses separately on different days. Repeated inhalations of doubling doses of PAF caused sGaw and FEV1 to plateau after the second dose in each group, whereas methacholine provoked a dose-related decrease in sGaw and FEV1. A dose-dependent decrease in the functional indices was restored when the different doses of PAF were administered on separate days. In both groups, the fall in sGaw after inhalation of 60 micrograms as a single dose was higher than that achieved when this dose was given during a full bronchial challenge. The falls in sGaw and FEV1 after PAF inhalation were significantly higher in the asthmatics than in the normal subjects. The provocative dose of PAF causing a 35% fall in sGaw (PD35,sGaw) PAF was only twofold lower in the asthmatics than in the normal subjects (p &lt; 0.05), while it was 11 fold lower for methacholine (p &lt; 0.001). When the PD35,sGaw values were compared, PAF was found on a molar basis to be 33 fold more potent than methacholine in the normal subjects, but only fivefold more potent in the asthmatics (p &lt; 0.05). The percentage falls in FEV1 (calculated by interpolation) for a 35% fall in sGaw, were greater in asthmatics than in normals both for methacholine (p &lt; 0.05) and PAF (p = 0.09). Our results demonstrate a tachyphylaxis after inhalation of platelet-activating factor in normal subjects and asthmatics, and show that asthmatics develop a greater bronchial obstruction than normal subjects even if methacholine is more sensitive than platelet-activating factor at discriminating between the two groups.
Time course of exercise capacity, skeletal and respiratory muscle performance after heart-lung transplantation
Authors: N Ambrosino, C Bruschi, G Callegari, S Baiocchi, G Felicetti, C Fracchia, C Rampulla
Journal: European Respiratory Journal (1996)

Recipients of heart-lung transplantation (HLT) show reduced exercise capacity due to several pre- and postsurgical factors. The aim of this study was to evaluate the time course of exercise capacity, and skeletal and respiratory muscle performance in 11 patients (5 females and 6 males; age (mean +/- SD) 38 +/- 13 yrs) undergoing HLT. All of the patients were admitted to our institution for a rehabilitation programme after surgery, and were followed-up for 18 months. On admission, at discharge after an in-patient rehabilitation programme, and every 6 months, patients underwent evaluation of: lung function values; incremental treadmill exercise, 6 min walking distance (6-MWD); maximal inspiratory and expiratory pressures (MIP and MEP, respectively); and peak torque of isokinetic contraction of leg flexor and extensor muscles (IFX and IEX, respectively). On admission, patients had: reduced lung volumes as assessed by vital capacity (VC) (60 +/- 15% of predicted); reduced exercise capacity as assessed by peak oxygen consumption (V'O2,peak) (40 +/- 12% pred); reduced skeletal and respiratory muscle performance as assessed by IEX, IFX (48 +/- 16 and 28 +/- 12 Newton-metres (N x m), respectively) and by MIP and MEP (54 +/- 21 and 58 +/- 19 cmH2O, respectively). Ten patients completed the rehabilitation programme. At discharge, no significant change in dynamic and static lung volumes was observed. However, nonsignificant increases in MIP, MEP, IEX, IFX, 6-MWD and V'O2,peak were recorded. After 6 and 12 months, indices of skeletal and respiratory muscle function and V'O2, peak improved further, but still remained lower than normal values. We conclude that in patients with heart-lung transplantation, skeletal and respiratory muscle function and exercise performance are reduced after surgery, that they may improve with time but are still less than normal after 18 months.
Acute exacerbations in patients with COPD: predictors of need for mechanical ventilation
Authors: M Vitacca, E Clini, R Porta, K Foglio, N Ambrosino
Journal: European Respiratory Journal (1996)

Predictive factors in mechanically-ventilated patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) have been extensively studied but not in spontaneously breathing patients. The aim of this retrospective study was to evaluate the contribution of parameters of respiratory mechanics, clinical and nutritional status in predicting the need for mechanical ventilation (MV) in COPD patients treated with medical therapy for an acute exacerbation. Anthropometric data, Acute Physiology and Chronic Health Evaluation (APACHE) II score, bedside spirometry, breathing pattern, respiratory mechanics and blood gases were measured in 39 COPD patients upon hospital admission for exacerbation of their disease. Fourteen patients in whom MV was necessary were compared with 25 patients in whom medical therapy was enough for a good outcome. The discriminant analysis showed, with decreasing order of power, that nutritional prognostic index (NPI), APACHE II score, forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio, vital capacity (VC) (% predicted) and FVC (% pred) provided a significant distinction between the two groups. The discriminant equation considering NPI, and FVC (% pred) could correctly predict the success in 76% of the patients. A multiparametric stepwise regression analysis showed that APACHE II score was significantly correlated with NPI, VC (% pred), pressure time index (PTI) and duty cycle, i.e. fraction of inspiration to duration of total breathing cycle (tl/ttot). In conclusion, underlying general conditions as assessed by malnutrition and APACHE II score were shown to be unfavourable indices of outcome for chronic obstructive pulmonary disease patients who experienced an exacerbation of their disease and were treated with medical therapy. Flow limitation data as assessed by the forced expiratory manoeuvre may provide additional information.