Miracle-dz/UniFAR-FTUs huggingface dataset:
Early and Intensive Motor Training for people with spinal cord injuries (the SCI-MT Trial): protocol of the process evaluation

Introduction People with spinal cord injury receive physical rehabilitation to promote neurological recovery. Physical rehabilitation commences as soon as possible when a person is medically stable. One key component of physical rehabilitation is motor training. There is initial evidence to suggest that motor training can enhance neurological recovery if it is provided soon after injury and in a high dosage. The Early and Intensive Motor Training Trial is a pragmatic randomised controlled trial to determine whether 10 weeks of intensive motor training enhances neurological recovery for people with spinal cord injury. This pragmatic randomised controlled trial will recruit 220 participants from 15 spinal injury units in Australia, Scotland, Italy, Norway, England, Belgium and the Netherlands. This protocol paper describes the process evaluation that will run alongside the Early and Intensive Motor Training Trial. This process evaluation will help to explain the trial results and explore the potential facilitators and barriers to the possible future rollout of the trial intervention. Methods and analysis The UK Medical Research Council process evaluation framework and the Implementation Research Logic Model will be used to explain the trial outcomes and inform future implementation. Key components of the context, implementation and mechanism of impact, as well as the essential elements of the intervention and outcomes, will be identified and analysed. Qualitative and quantitative data will be collected and triangulated with the results of the Early and Intensive Motor Training Trial to strengthen the findings of this process evaluation. Ethics and dissemination Ethical approval for the Early and Intensive Motor Training Trial and process evaluation has been obtained from the Human Research Ethics Committee at the Northern Sydney Local Health District (New South Wales) in Australia (project identifier: 2020/ETH02540). All participants are required to provide written consent after being informed about the trial and the process evaluation. The results of this process evaluation will be published in peer-reviewed journals. Trial registration number Australian New Zealand Clinical Trial Registry (ACTRN12621000091808); Universal Trial Number (U1111-1264-1689).
Impact of first and second eye cataract surgery on physical activity: a prospective study

Objectives To investigate the impact of first eye and second eye cataract surgery on the level of physical activity undertaken by older adults with bilateral cataract. Design Prospective cohort study. Setting Three public ophthalmology clinics in Western Australia. Participants Fifty-five older adults with bilateral cataract aged 55+ years, awaiting first eye cataract surgery. Outcome measures The primary outcome measure was participation in moderate leisure-time physical activity. The secondary outcomes were participation in walking, gardening and vigorous leisure-time physical activity. Participants completed a researcher-administered questionnaire, containing the Active Australia Survey and visual tests before first eye cataract surgery, after first eye surgery and after second eye surgery. A Generalised Estimating Equation linear regression model was undertaken to analyse the change in moderate leisure-time physical activity participation before first eye surgery, after first eye surgery and after second eye surgery, after accounting for relevant confounders. Results Participants spent significantly less time per week (20 min) on moderate leisure-time physical activity before first eye cataract surgery compared with after first eye surgery (p=0.04) after accounting for confounders. After second eye cataract surgery, participants spent significantly more time per week (32 min) on moderate physical activity compared with after first eye surgery (p=0.02). There were no significant changes in walking, gardening and vigorous physical activity throughout the cataract surgery process. Conclusion First and second eye cataract surgery each independently increased participation in moderate leisure-time physical activity. This provides a rationale for timely first and second eye cataract surgery for bilateral cataract patients, even when they have relatively good vision.
Effect of right anterolateral thoracotomy versus median sternotomy on postoperative wound tissue repair in patients with congenital heart disease: A meta‐analysis

Abstract Right anterolateral thoracotomy (RAT) and median sternotomy (MS) are two major methods for treatment of congenital cardiac disease. But there are various types of surgery that provide a better operative outcome for the patient. Therefore, we carried out a meta‐analysis to investigate the effects of these two methods in the treatment of wound tissue, hospitalization and so on, to find out which surgery method could provide the best short‐term effect. In this research, we chose an English controlled trial from 2003 to 2022 to evaluate the influence of right anterolateral thoracotomy and median sternotomy on the short‐term outcome of Cardiopulmonary bypass (CPB), time of operation, time spent in the hospital, and the time of scar formation. Our findings suggest that the RAT method was associated with a shorter surgical scars for congenital heart disease operations compared to MS with respect to post‐operation scars (WMD, 3.55; 95% CI, 0.04, 7.05; p = 0.05). The RAT method is better suited to the needs of patients who care about their injuries. Nevertheless, in addition to other surgery related factors which might affect post‐operative wound healing, we discovered that MS took a shorter time to perform CPB compared with RAT surgery (WMD, − 1.94; 95% CI, −3.39, −0.48; p = 0.009). Likewise, when it comes to the time taken to perform surgery, MS needs less operational time compared to RAT methods (WMD, −12.84; 95% CI, −25.27, −0.42; p = 0.04). On the other hand, the time needed for MS to recover was much longer compared to the RAT (WMD, 0. 60; 95% CI, 0.02, 1.18; p = 0.04). This indicates that while RAT is advantageous in terms of shortening the duration of post‐operative scar, it also increases the time needed for surgical operations and CPB.
The tryptophan–kynurenine pathway in immunomodulation and cancer metastasis

The activation of the kynurenine pathway in cancer progression and metastasis through immunomodulatory pathways has drawn attention to the potential for kynurenine pathway inhibition. The activation of the kynurenine pathway, which results in the production of kynurenine metabolites through the degradation of tryptophan, promotes the development of intrinsically malignant properties in cancer cells while facilitating tumour immune escape. In addition, kynurenine metabolites act as biologically active substances to promote cancer development and metastasis.
Association of Supine Hypertension Versus Standing Hypotension With Adverse Events Among Middle-Aged Adults

BACKGROUND: Management of orthostatic hypotension (OH) prioritizes prevention of standing hypotension, sometimes at the expense of supine hypertension. It is unclear whether supine hypertension is associated with adverse outcomes relative to standing hypotension. OBJECTIVES: To compare the long-term clinical consequences of supine hypertension and standing hypotension among middle-aged adults with and without OH. METHODS: The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing blood pressure (BP) in adults aged 45 to 64 years, without neurogenic OH, between 1987 and 1989. We defined OH as a positional drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg, supine hypertension as supine BP≥140/≥90 mm Hg, and standing hypotension as standing BP≤105/≤65 mm Hg. Participants were followed for >30 years. We used Cox regression models to examine associations with cardiovascular disease events, all-cause mortality, falls, and syncope. RESULTS: Of 12 489 participants (55% female, 26% Black, mean age 54 years, SD 6), 4.4% had OH. Among those without OH (N=11 943), 19% had supine hypertension and 21% had standing hypotension, while among those with OH (N=546), 58% had supine hypertension and 38% had standing hypotension. Associations with outcomes did not differ by OH status (P-interactions >0.25). Supine hypertension was associated with heart failure (hazard ratio, 1.83 [95% CI, 1.68–1.99]), falls (hazard ratio, 1.12 [95% CI, 1.02–1.22]), and all-cause mortality (hazard ratio, 1.45 [95% CI, 1.37–1.54]), while standing hypotension was only significantly associated with mortality (hazard ratio, 1.06 [95% CI, 1.00–1.14]). CONCLUSIONS: Supine hypertension was associated with higher risk of adverse events than standing hypotension, regardless of OH status. This challenges conventional OH management, which prioritizes standing hypotension over supine hypertension.
Survival outcomes and prognostic nutritional index in very elderly small-cell lung cancer patients: importance of active treatment and nutritional support

Abstract Background Small-cell lung cancer (SCLC) is a highly aggressive tumor with a high metastatic potential, particularly affecting current or former heavy smokers. Treatment typically involves chemotherapy, often combined with radiotherapy, and immunotherapy for extensive disease. Prophylactic cranial irradiation is recommended to reduce brain metastases. Elderly SCLC patients face unique challenges due to frailty and comorbidities, leading to increased risks of treatment-related toxicity and malnutrition. The prognostic nutritional index (PNI), a composite marker of nutritional and immune status, has shown promise in predicting outcomes in various malignancies. However, the optimal treatment approach for very elderly SCLC patients remains unclear, as they are often excluded from clinical trials. Aims This study aimed to evaluate the survival outcomes of SCLC patients aged 75 years or older and their correlation with PNI. Study design Retrospective cohort study. Methods The study retrospectively analyzed data from 71 SCLC patients aged ≥75 years, focusing on age, gender, smoking status, chronic diseases, performance status, clinical stage, treatment modality, and pretreatment PNI. Survival estimates were calculated using the Kaplan–Meier method, and multivariate Cox regression analysis was performed to identify independent predictors of overall survival (OS). Results The results demonstrated that 26.8% of very elderly SCLC patients received no active treatment, resulting in a significantly shorter median survival time of 1.3 months. In contrast, patients who underwent aggressive treatment, such as palliative chemotherapy or chemotherapy plus radiotherapy, had significantly longer median survival times. Multivariate analysis revealed that receiving chemotherapy plus radiotherapy was associated with a significant survival benefit compared to no treatment. Furthermore, low PNI (≤40) was independently associated with decreased OS. Conclusion This study highlights the importance of active treatment and nutritional support in improving survival outcomes for very elderly SCLC patients. The findings suggest that low PNI and lack of oncological treatment are associated with worse survival outcomes. Therefore, integrating nutritional assessment, interventions, and appropriate treatment strategies are crucial in managing lung cancer patients. Larger, multicenter studies are needed to validate these findings and explore potential interventions to optimize nutritional status and improve outcomes for elderly patients with SCLC.
Understanding the molecular pathogenesis of primary central nervous system lymphoma by experimental animal models

Primary central nervous system lymphoma (PCNSL) is a rare and invasive diffuse large B cell lymphoma confined in central nervous system (CNS). The effort to press forward the translational progress has been frustrated by the insufficient understanding of immunophenotype of CNS and tumor genetic alterations of PCNSL, and the lack of validated diagnostic biomarkers. Researchers now have a variety of PCNSL animal models at their disposal that resemble the morphology and immunophenotype of PCNSL, however, a careful and detailed re‐examination of these animal models is needed to clarify the differences in genetic alterations, migration capability, and immune status. In this review, we present the knowledge about the phenotypic and genotypic features of PCNSL tumor cells, and compile the preclinical animal models of PCNSL with regard to various injection sites, cell origins, recipient animals, and immune status, and elaborate on the tropism and migration of tumor cells and novel therapeutic strategies for PCNSL. We envisage that the selection of suitable animal models will serve as a well‐defined preclinical system to understand the molecular pathogenesis of PCNSL, thereby galvanizing the development of novel and potent therapeutic approaches.
Tailoring cognitive behavioural therapy for insomnia across contexts, conditions, and individuals: What do we know, where do we go?

Cognitive behavioural therapy for insomnia (CBT‐I) is considered the front‐line treatment for insomnia. Despite the demonstrated effectiveness of CBT‐I, it is necessary to consider how CBT‐I may be tailored to different individuals. The purpose of the present review is to provide a summary of literature on tailoring CBT‐I to different individuals and provide directions for future research. This review focused on the following domains of adaptation: (i) tailoring CBT‐I components to individuals with comorbid mental or physical health conditions such as comorbid depression and pain; (ii) adapting CBT‐I delivery for different contexts in which individuals exist, such as inpatient, educational, and different social/cultural settings, (iii) adapting CBT‐I to specific individuals via case‐formulation in clinical settings. We highlight current gaps in the exploration of tailored CBT‐I, including a lack of research methodology to evaluate tailored interventions, a need for the integration of ongoing individualised assessment to inform treatment, and the necessary involvement of consumers and stakeholders throughout the research and treatment development process. Together, this review showed abundant adaptations in CBT‐I already exist in the literature. Future research is needed in understanding when and how to apply adaptations in CBT‐I and evaluate the benefits of these adaptations.
Efficacy and safety of bevacizumab-based combination therapy for treatment of patients with metastatic colorectal cancer

Aim: The use of bevacizumab in combination therapy is an emerging trend in metastatic colorectal cancer treatment. However, the clinical value of different combination types remains under debate. Thus, a meta-analysis of randomized controlled trials (RCTs) comparing bevacizumab-based combination therapy with monotherapy (therapy that uses one type of treatment, such as chemotherapy or surgery alone, to treat metastatic colorectal cancer) was performed, aiming to evaluate the safety and efficacy of bevacizumab-based combination therapy and to find a more beneficial combination. Methods: We searched for clinical studies that evaluated bevacizumab-based combination therapy in metastatic colorectal cancer. We extracted data from these studies to evaluate the relative risk (RR) of overall response rate (ORR) and grade 3/4 treatment-related adverse events (AEs), HRs of overall survival (OS), and progression-free survival (PFS). Results: Eight RCTs were identified (n = 3,424). Treatments included combinations of bevacizumab and oxaliplatin, fluorouracil, and leucovorin (FOLFOX4), combinations of bevacizumab and capecitabine and oxaliplatin, combinations of bevacizumab and fluorouracil/leucovorin, combinations of bevacizumab and irinotecan, fluorouracil, and leucovorin (IFL), and combinations of bevacizumab and capecitabine. Bevacizumab-based combination therapy showed higher ORR (RR: 1.40; 95% CI: 1.10–1.78; P = 0.005), PFS (HR: 0.64; 95% CI: 0.55–0.73; P = 0.000), and OS (HR: 0.82; 95% CI: 0.73–0.92; P = 0.001) values than monotherapy. However, higher grade 3/4 treatment-related AEs (RR: 1.27; 95% CI: 1.15–1.41; P = 0.000) were observed in combination therapy than in monotherapy. Conclusion: This meta-analysis showed that the addition of IFL to bevacizumab better benefits PFS and safety. Adding FOLFOX4 was associated with better ORR and OS. The efficacy and safety of an IFL–bevacizumab–FOLFOX4 combination should be given greater weight in future clinical trials, guidelines, and clinical practice.
Analyse et modélisation des courants et de la turbulence sous les vagues de vent

Deux manifestations relativement bien observees des interactions dynamiques a l'interface eau-atmosphere sont au centre de ce travail : il s'agit d'une part, du niveau eleve de l'intensite turbulente au sommet de la couche de surface, sous les vagues de vent, d'autre part, de l'organisation du champ de vitesse moyenne en rouleaux d'axes paralleles a la direction du vent (circulations de Langmuir). Ce double aspect des interactions entre les courants moyens, la turbulence et les mouvements orbitaux associes aux vagues est analyse en mettant en oeuvre une modelisation et des simulations numeriques qui s'appuient sur un ensemble de resultats experimentaux obtenus au laboratoire ou sur le terrain. Les principaux travaux theoriques et experimentaux qui ont contribue a mieux apprehender ces aspects de la dynamique de la couche melangee de surface et sur lesquels s'appuient les essais de modelisation sont rappeles et commentes dans le premier chapitre du memoire. Les resultats d'experiences de laboratoire et de terrain disponibles ont ete recenses et compares. Cette analyse est developpee sous forme non dimensionnelle avec des echelles de reference caracteristiques des trois mouvements, orbital, turbulent et moyen. Les resultats presentes dans le chapitre deux suggerent ainsi une nouvelle parametrisation de l'energie cinetique turbulente et du taux de dissipation turbulente au sommet de la couche de surface en fonction de l'energie, de la cambrure et du nombre d'onde de l'onde dominante du champ de vagues (ces resultats vont guider le choix des conditions aux limites a l'interface mises en oeuvre dans les experiences numeriques). Cette analyse confirme aussi, du moins qualitativement, le role des circulations de Langmuir sur le champ de vitesse moyenne et la turbulence.
Type 2 diabetes remission trajectories and variation in risk of diabetes complications: A population-based cohort study

Biochemical remission of type 2 diabetes is achievable through dietary changes, physical activity and subsequent weight loss. We aim to identify distinct diabetes remission trajectories in a large population-based cohort over seven-years follow-up and to examine associations between remission trajectories and diabetes complications. Group-based trajectory modelling examined longitudinal patterns of HbA1c level (adjusting for remission status) over time. Multivariable Cox models quantified the association between each remission trajectory and microvascular complications, macrovascular complications, cardiovascular (CVD) events and all-cause mortality. Four groups were assigned. Group 1 (8,112 [13.5%]; achieving HbA1c <48 mmol/mol (6.5%) followed by increasing HbA1c levels); Group 2 (6,369 [10.6%]; decreasing HbA1c levels >48 mmol/mol (6.5%)); Group 3 (36,557 [60.6%]; stable high HbA1c levels); Group 4 (9,249 [15.3%]; stable low HbA1c levels (<48mmol/mol or <6.5%)). Compared to Group 3, Groups 1 and 4 had lower risk of microvascular complications (aHRs (95% CI): 0.65 (0.61–0.70), p-value <0.001;0.59 (0.55–0.64) p-value<0.001, respectively)), macrovascular complications (aHRs (95% CI): 0.83 (0.75–0.92), p-value<0.001; 0.66 (0.61–0.71), p-value<0.001) and CVD events (aHRs (95% CI): 0.74(0.67–0.83), p-value<0.001; 0.67(0.61–0.73), p-vlaue<0.001). Risk of CVD outcomes were similar for Groups 2 and 3. Compared to Group 3, Group 1 (aHR: 0.82(95% CI: 0.76–0.89)) had lower risk of mortality, but Group 4 had higher risk of mortality (aHR: 1.11(95% CI: 1.03–1.19)). Risk of CVD outcomes vary by pattern of remission over time, with lowest risk for those in remission longer. People who achieve remission, even for shorter periods of time, continue to benefit from this lower exposure to hyperglycaemia, which may, in turn, lower the risk of CVD outcomes including mortality.
The Teenage Brain

In this article, we explore the emerging and potential influence of adolescent brain science on law and public policy. The primary importance of this research is in policy domains that implicate adolescent risk taking; these include drug and alcohol use, driver licensing, and criminal justice. We describe the emerging importance of brain science in the Supreme Court and other policy arenas. Finally, we argue that current research cannot contribute usefully to legal decisions about individual adolescents and should not be used in criminal trials at the present time, except to provide general developmental information.
Clinical and Vessel Characteristics Associated With Hard Outcomes After PCI and Their Combined Prognostic Implications

Background Cardiac death or myocardial infarction still occurs in patients undergoing contemporary percutaneous coronary intervention (PCI). We aimed to identify adverse clinical and vessel characteristics related to hard outcomes after PCI and to investigate their individual and combined prognostic implications. Methods and Results From an individual patient data meta‐analysis of 17 cohorts of patients who underwent post‐PCI fractional flow reserve measurement after drug‐eluting stent implantation, 2081 patients with available clinical and vessel characteristics were analyzed. The primary outcome was cardiac death or target‐vessel myocardial infarction at 2 years. The mean age of patients was 64.2±10.2 years, and the mean angiographic percent diameter stenosis was 63.9%±14.3%. Among 11 clinical and 8 vessel features, 4 adverse clinical characteristics (age ≥65 years, diabetes, chronic kidney disease, and left ventricular ejection fraction <50%) and 2 adverse vessel characteristics (post‐PCI fractional flow reserve ≤0.80 and total stent length ≥54 mm) were identified to independently predict the primary outcome (all P<0.05). The number of adverse vessel characteristics had additive predictability for the primary end point to that of adverse clinical characteristics (area under the curve 0.72 versus 0.78; P=0.03) and vice versa (area under the curve 0.68 versus 0.78; P=0.03). The cumulative event rate increased in the order of none, either, and both of adverse clinical characteristics ≥2 and adverse vessel characteristics ≥1 (0.3%, 2.4%, and 5.3%; P for trend <0.01). Conclusions In patients undergoing drug‐eluting stent implantation, adverse clinical and vessel characteristics were associated with the risk of cardiac death or target‐vessel myocardial infarction. Because these characteristics showed independent and additive prognostic value, their integrative assessment can optimize post‐PCI risk stratification. Registration URL: https://www.clinicaltrials. gov; Unique identifier: NCT04684043. www.crd. york.ac. uk/prospero/. Unique Identifier: CRD42021234748.