Miracle-dz/UniFAR-FTUs huggingface dataset:
Electrical Resynchronization and Clinical Outcomes During Long-Term Follow-Up in Intraventricular Conduction Delay Patients Applied Left Bundle Branch Pacing-Optimized Cardiac Resynchronization Therapy

BACKGROUND: Left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT) has shown encouraging results for QRS duration reduction and heart function improvement. However, the feasibility and efficacy of LOT-CRT have not been well established in intraventricular conduction delay patients. This study aims to assess and compare the efficacy and clinical outcome of CRT based on left bundle branch pacing, combined with coronary sinus left ventricular pacing (LOT-CRT) with CRT via biventricular pacing (BiV-CRT) in intraventricular conduction delay patients indicated for CRT. METHODS: Consecutive patients with intraventricular conduction delay and CRT indications were assigned nonrandomized to LOT-CRT (n=30) or BiV-CRT (n=55). Addition of the left bundle branch pacing (or coronary venous) lead was at the discretion of the implanting physician guided by suboptimal paced QRS complex and on clinical grounds. Echocardiographic parameters and clinical characteristics were accessed at baseline and during 2-years’ follow-up. RESULTS: Success rate for LOT-CRT and BiV-CRT was 96.8% and 96.4%. LOT-CRT had greater reduction of QRS duration compared with BiV-CRT (42.7±17.4 ms versus 21.9±21.5 ms; P<0.001). Higher left ventricular ejection fraction was also achieved in LOT-CRT than BiV-CRT at 6-month (36.7±9.8% versus 30.5±6.4%; P<0.05), 12-month (34.8±7.6% versus 30.3±6.2%; P<0.05), 18-month (36.3±7.9% versus 28.1±6.6%; P<0.005), and 24-month follow-up (37±9.5% versus 30.5±7%; P<0.05). Adverse clinical outcomes including heart failure rehospitalization and mortality were lower in LOT-CRT group for 24 months follow-up (hazard ratio, 0.33; P=0.035). CONCLUSIONS: LOT-CRT improves ventricular electrical synchrony and may provide greater clinical outcomes as compared with BiV-CRT in intraventricular conduction delay patients. These findings need further evaluation in future randomized controlled trials.
Epidemiology of spinal muscular atrophy caused by SMN1 deletions in Maritime Canada

Spinal muscular atrophy (SMA), caused primarily by deletions in SMN1, leads to progressive loss of lower motor neurons. Newborn screening for SMA is under consideration for the Maritime Newborn Screening Program. The incidence of this disease has not been explored in Maritime Canada which includes the provinces of Nova Scotia (NS), New Brunswick (NB), and Prince Edward Island (PEI). In this retrospective chart review, patients were identified from the IWK Clinical Genomics Lab and Maritime Medical Genetics Service databases for SMN1 genetic testing between 2000 and 2020. The incidence of SMA in Maritime Canada was 1:11,900. Among patients born between 2000 and 2020, NB and PEI had lower proportions of type 1 SMA (12% and 0%, respectively) when compared to NS (50%). The majority of type 1 patients had 2 copies of SMN2, the majority of type 2 patients had 3 copies, and the majority of type 3 patients had 4 copies. There was a delay to molecular diagnosis for all subtypes, longest in type 3. This study provides the best available SMA epidemiology in Maritime Canada and expands our understanding of the pattern of disease severity relative to SMN2 copy number in this region.
Phlorizin attenuates postoperative gastric ileus in rats

Postoperative ileus (POI) is a major complication of abdominal surgery (AS). Impaired gut barrier mediated via Toll‐like receptor 4 (TLR4) and interleukin‐1 (IL‐1) receptor is involved in the development of POI. Phlorizin is a nonselective inhibitor of sodium‐linked glucose transporters (SGLTs) and is known to improve lipopolysaccharide (LPS)‐induced impaired gut barrier. This study aimed to clarify our hypothesis that AS‐induced gastric ileus is mediated via TLR4 and IL‐1 signaling, and phlorizin improves the ileus.
Integrated Multimodal Analyses of DNA Damage Response and Immune Markers as Predictors of Response in Metastatic Triple-Negative Breast Cancer in the TNT Trial (NCT00532727)

Abstract Purpose: The TNT trial (NCT00532727) showed no evidence of carboplatin superiority over docetaxel in metastatic triple-negative breast cancer (mTNBC), but carboplatin benefit was observed in the germline BRCA1/2 mutation subgroup. Broader response-predictive biomarkers are needed. We explored the predictive ability of DNA damage response (DDR) and immune markers. Experimental Design: Tumor-infiltrating lymphocytes were evaluated for 222 of 376 patients. Primary tumors (PT) from 186 TNT participants (13 matched recurrences) were profiled using total RNA sequencing. Four transcriptional DDR-related and 25 immune-related signatures were evaluated. We assessed their association with objective response rate (ORR) and progression-free survival (PFS). Conditional inference forest clustering was applied to integrate multimodal data. The biology of subgroups was characterized by 693 gene expression modules and other markers. Results: Transcriptional DDR-related biomarkers were not predictive of ORR to either treatment overall. Changes from PT to recurrence were demonstrated; in chemotherapy-naïve patients, transcriptional DDR markers separated carboplatin responders from nonresponders (P values = 0.017; 0.046). High immune infiltration was associated with docetaxel ORR (interaction P values < 0.05). Six subgroups were identified; the immune-enriched cluster had preferential docetaxel response [62.5% (D) vs. 29.4% (C); P = 0.016]. The immune-depleted cluster had preferential carboplatin response [8.0% (D) vs. 40.0% (C); P = 0.011]. DDR-related subgroups were too small to assess ORR. Conclusions: High immune features predict docetaxel response, and high DDR signature scores predict carboplatin response in treatment-naïve mTNBC. Integrating multimodal DDR and immune-related markers identifies subgroups with differential treatment sensitivity. Treatment options for patients with immune-low and DDR-proficient tumors remains an outstanding need. Caution is needed using PT-derived transcriptional signatures to direct treatment in mTNBC, particularly DDR-related markers following prior chemotherapy.
Exploiting nanopore sequencing for characterization and grading of IDH‐mutant gliomas

The 2021 WHO Classification of Central Nervous System Tumors recommended evaluation of cyclin‐dependent kinase inhibitor 2A/B (CDKN2A/B) deletion in addition to codeletion of 1p/19q to characterize IDH‐mutant gliomas. Here, we demonstrated the use of a nanopore‐based copy‐number variation sequencing (nCNV‐seq) approach to simultaneously identify deletions of CDKN2A/B and 1p/19q. The nCNV‐seq approach was initially evaluated on three distinct glioma cell lines and then applied to 19 IDH‐mutant gliomas (8 astrocytomas and 11 oligodendrogliomas) from patients. The whole‐arm 1p/19q codeletion was detected in all oligodendrogliomas with high concordance among nCNV‐seq, FISH, DNA methylation profiling, and whole‐genome sequencing. For the CDKN2A/B deletion, nCNV‐seq detected the loss in both astrocytoma and oligodendroglioma, with strong correlation with the CNV profiles derived from whole‐genome sequencing (Pearson correlation (r) = 0.95, P < 2.2 × 10−16 to r = 0.99, P < 2.2 × 10−16) and methylome profiling. Furthermore, nCNV‐seq can differentiate between homozygous and hemizygous deletions of CDKN2A/B. Taken together, nCNV‐seq holds promise as a new, alternative approach for a rapid and simultaneous detection of the molecular signatures of IDH‐mutant gliomas without capital expenditure for a sequencer.
Evaluation of Experiences and Attitudes of Patients Towards Patient Portal–Enabled Access to Their Health Information or Medical Records: A Qualitative Grounded Theory Study

The demand for patient-centred care and patient engagement in their healthcare has driven patient portal introduction. The widespread adoption and use of patient portals, however, has been a rather slow process in the United Kingdom. Hence, a limited number of studies have explored patient perceptions and experiences of general portal use, which forms a foundation for successful implementation of a portal. This study, therefore, focuses on the experiences and attitudes of patients regarding use of patient portals and access to their health information. It further explores various factors perceived by patients that may influence portal use and uptake. The overall findings from this study highlight positive patient perceptions of portal use. Nevertheless, it demonstrates various areas of improvement essential to ensure future success of portal implementation and acceptance.
European Neuroendocrine Tumor Society 2023 guidance paper for functioning pancreatic neuroendocrine tumour syndromes

This ENETS guidance paper aims to provide practical advice to clinicians for the diagnosis, treatment and follow‐up of functioning syndromes in pancreatic neuroendocrine tumours (NET). A NET‐associated functioning syndrome is defined by the presence of a clinical syndrome combined with biochemical evidence of inappropriately elevated hormonal levels. Different hormonal syndromes can be encountered in pancreatic NET patients, including insulinoma, gastrinoma as well as the rare glucagonoma, VIPoma, ACTHoma, PTHrPoma, carcinoid syndrome, calcitoninoma, GHRHoma and somatostatinoma. The recommendations provided in this paper focus on the biochemical, genetic and imaging work‐up as well as therapeutic management of the individual hormonal syndromes in well‐differentiated, grade 1‐3, functioning NET with the primary tumour originating in the pancreas, and for specific subtypes also in the duodenum.
Dietary palmitic acid to oleic acid ratio modulates energy metabolism and biological rhythms in young healthy Japanese males

Abstract The present study investigated the potential role of the composition of dietary fatty acids in the regulation of biological rhythms, such as the sleep architecture, core body temperature and leukocyte clock gene expression, in subjects fed meals rich in palmitic acid (PA) or oleic acid (OA). Eleven males participated in two sessions of indirect calorimetry in a whole-room metabolic chamber. In each session, subjects consumed three meals rich in PA (44·3 % of total fat as PA and 42·3 % as OA) or OA (11·7 % of total fat as PA and 59·3 % as OA) in the metabolic chamber. The ratio of PA to OA in plasma was significantly lower and fat oxidation was significantly higher during 24 h of indirect calorimetry in the session with meals rich in OA than in that with meals rich in PA. The duration of slow wave sleep (SWS) was shorter, the latency of SWS was longer and the nadir of core body temperature after bedtime was later in the session with meals rich in PA than in that with meals rich in OA. The peak in CRY1 gene expression was earlier and its amplitude was higher in the session with meals rich in PA than in that with meals rich in OA. In healthy young males, meals rich in PA decreased fat oxidation and disrupted biological rhythms, particularly the sleep architecture and core body temperature during sleep, more than meals rich in OA.
A Question of Trust: An Ethnographic Study of Automated Cars on Real Roads

Recent technological advances in automated cars have brought them closer to regular use on the roads. Accordingly, research on the driver's perspective is increasing. However, previous studies have limitations in terms of the length of the study period and richness of the user's experience. In this paper, we conducted an ethnographic experiment to observe the interaction between humans and automated cars. Six participants rode in a prototype automated car on a real road one hour a day for six days under various weather conditions. We found that even after six days of utilizing it, participants did not fully trust the automated car. We identified nine distrust factors that strongly influenced their experiences in the automated car, classifying them according to Lee and See's classification of three trust categories: process, performance, and purpose. We also present serval ideas based on the study results.
Resource enclavity and corporate social responsibility in Sub-Saharan Africa : the case of oil production in Ghana

Why has Corporate Social Responsibility (CSR) yielded such disappointing outcomes in oil-rich sub-Saharan Africa? Over the past decades, a sizable body of literature has emerged which draws attention to the shortcomings of oil-related development and complementary CSR exercises in the region. Most critiques on the topic, however, assess specific interventions and/or policies but fail to evaluate the complex decision-making processes, dictated heavily by setting, which produce such actions altogether. This thesis attributes CSR outcomes in oil-rich sub-Saharan Africa to the unique context in which the decisions underpinning actions take place. In doing so, the analysis borrows ideas from a diverse body of literature spanning the international development, accounting, management and political science disciplines. To explore these ideas further, the thesis focuses on the case of Ghana. The most recent “addition” to sub-Saharan Africa’s oil club, Ghana provides a rare glimpse of how decisions underpinning CSR have been identified, evolved and reshaped from the outset. To provide a comprehensive picture of CSR in the sector and its impacts at the local level, interviews and focus groups were conducted with a range of stakeholder groups. As is the case throughout sub-Saharan Africa, in Ghana, oil production occurs in offshore “enclaves”, which are disconnected geographically from local communities. This thesis argues that these dynamics have important implications for CSR. Findings point to companies also being disconnected ideologically from local development needs, which, in part explains the questionable CSR that has become such a contentious issue in the debate on oil and development in sub-Saharan Africa in recent years. The enclave-type setting in which oil production occurs appears to have stifled creativity and innovation in the area of CSR. This, along with institutional weaknesses, regulatory deficiencies and the Government of Ghana’s failure to adequately respond to local-level concerns, has produced these outcomes.
Melanoma literacy among the general population of three western US states

Melanoma is a significant cause of cancer death, despite being detectable without specialized or invasive technologies. Understanding barriers to preventive behaviors such as skin self‐examination (SSE) could help to define interventions for increasing the frequency of early detection. To determine melanoma knowledge and beliefs across three high‐incidence US states, 15,000 surveys were sent to a population‐representative sample. We aimed to assess (1) melanoma literacy (i.e., knowledge about melanoma risks, attitudes, and preventive behaviors) and (2) self‐reported SSE and its association with melanoma literacy, self‐efficacy, and belief in the benefits of SSE. Of 2326 respondents, only 21.2% provided responses indicating high knowledge of melanoma, and 62.8% reported performing an SSE at any time in their lives. Only 38.3% and 7.3% reported being “fairly” or “very” confident about doing SSE, respectively. SSE performance among respondents was most strongly associated with higher melanoma knowledge, higher self‐efficacy, and personal history of melanoma. Melanoma literacy among survey respondents was modest, with greater literacy associated with a higher likelihood of reported preventive behavior. This assessment establishes a baseline and provides guidance for public health campaigns designed to increase prevention and early detection of this lethal cancer.
Learnings from a prison‐based drug treatment program on planning for release: A qualitative study

Abstract Introduction Prison‐based drug and alcohol group treatment programs operate in all Australian jurisdictions. With more than two‐thirds of people in prison having a history of substance use prior to incarceration, such programs are needed. There have been few published papers on the impact of attending group treatment programs in Australian prisons, and the research published to date has been predominately quantitative. We aim to report the experiences of males in prison who completed and those who did not complete a group‐based drug and alcohol program, to gain insight into their strategies for reducing harm from drug and alcohol post‐release. Methods Qualitative thematic analysis of in‐depth interviews with 12 males who completed or were about to complete and 10 males who discontinued a prison‐based group drug and alcohol treatment program. Results Program completers were more likely to have well‐developed plans to reduce drug and alcohol harms and maintain abstinence upon return to the community, which included creating healthier social networks. They also showed stronger insights into the factors that led to offending. Those who did not complete the drug and alcohol program appeared to rely on self‐will as the main way to reduce drug and alcohol harms, with less awareness of options for support services to reduce or stop drug and alcohol use. Discussion and Conclusions Prison‐based drug and alcohol program engagement imparted useful information for program completers. Controlled trials are needed to examine whether such differences equate to improved outcomes after release.
Evaluating as-needed inhaled corticosteroid strategies in asthma: expanding the benefits to mild asthma

ABSTRACT Introduction Adherence to regular anti-inflammatory treatment is commonly low, and short-acting β2 agonist (SABA) overuse is common in patients with asthma, leading to an increased risk of asthma-related adverse events. Areas covered Given the pivotal role of inflammation in asthma, multiple as-needed inhaled corticosteroid (ICS)-containing therapies have been developed, leading to a reduction in asthma exacerbations and improvement in symptom control. Currently, as-needed ICS/formoterol is one of the most commonly available formulations; however, other combinations such as ICS/SABA have been shown to be superior to as-needed SABA alone. Therefore, we performed a comprehensive review of the available scientific literature to enhance the advantages and disadvantages of each combination in clinical practice. Expert opinion The future direction we foresee in asthma management consists in abandoning as-needed short-acting bronchodilators in favor of as-needed ICS-containing therapies. Each patient is unique and differs from others; consequently, a single option will not fit everyone. Patients’ and physicians’ awareness of this perspective can be reached through the development of multiple therapeutic options suitable for each condition that can be found in ‘real life’.
Beat the heat: Thermal respites and access to food associated with increased bumble bee heat tolerance.

Climate change poses a threat to organisms across the world, with cold-adapted species such as bumble bees (Bombus spp) at particularly high risk. Understanding how organisms respond to extreme heat events associated with climate change as well as the factors that increase resilience or prime organisms for future stress can inform conservation actions. We investigate the effects of heat stress within different contexts (duration, periodicity, with and without access to food, and in the laboratory versus field) on bumble bee (Bombus impatiens) survival and heat tolerance. We found that both prolonged (5 h) heat stress and nutrition limitation were negatively correlated with worker bee survival and thermal tolerance. However, the effects of these acute stressors were not long-lasting (no difference in thermal tolerance among treatment groups after 24 h). Additionally, intermittent heat stress, which more closely simulates the forager behavior of leaving and returning to the nest, was not negatively correlated with worker thermal tolerance. Thus, short respites may allow foragers to recover from thermal stress. Moreover, these results suggest there is no priming effect resulting from short or long duration exposure to heat - bees remained equally sensitive to heat in subsequent exposures. In field caught bumble bees, foragers collected during warmer vs. cooler conditions exhibited similar thermal tolerance after being allowed to recover in the lab for 16 h. These studies offer insight into the impacts of a key bumble bee stressor and highlight the importance of recovery duration, stressor periodicity, and context on bumble bee thermal tolerance outcomes.
Which is the More Effective Option for Pleurodesis to Prevent the Recurrence of Malignant Pleural Effusion? Large-Particle Talc or Mistletoe Extract (ABNOVA Viscum Injection)

Background Malignant pleural effusion affects many patients with advanced cancer. When chemotherapy or radiotherapy fails to relieve malignant pleural effusion and related symptoms, drainage and pleurodesis can help. Although surgical talc pleurodesis is the most widely used method, Viscum album, which has been recently used in surgical or bedside procedures, has demonstrated significant results and is as effective as talc. This study aimed to determine the most effective agent and procedure. Methods Between January 2015 and July 2022, chemical pleurodesis was performed in 137 patients with malignant pleural effusion, using a V. album surgical procedure in 48, a V. album bedside procedure in 55, and a talc surgical procedure in 34 patients. We reviewed patients’ clinical responses and disease progression after chemical pleurodesis. Results The success rate was not significantly different among the V. album surgical procedures (91.7%), V. album bedside procedures (83.6%), and talc surgical procedures (91.2%). However, the total drainage amount and tube insertion duration in both Viscum groups were more effective than those in the talc group. Furthermore, the bedside Viscum group showed significantly lower post-pleurodesis pain scores than the other 2 groups. Conclusion According to our results, talc and V. album can be considered ideal agents for chemical pleurodesis. However, Viscum pleurodesis showed safer outcomes in terms of ensuring quality of life than talc. Additionally, the bedside Viscum group showed significantly lower pain scores than the other groups. Hence, patients for whom surgical procedures are inappropriate can undergo bedside Viscum pleurodesis without diminishing the therapeutic effect.
Frequency and phenotypic spectrum of spinocerebellar ataxia 27B and other genetic ataxias in a Spanish cohort of late‐onset cerebellar ataxia

Dominantly inherited GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene have recently been shown to cause spinocerebellar ataxia 27B (SCA27B). We aimed to study the frequency and phenotype of SCA27B in a cohort of patients with unsolved late‐onset cerebellar ataxia (LOCA). We also assessed the frequency of SCA27B relative to other genetically defined LOCAs.