Miracle-dz/UniFAR-FTUs huggingface dataset:
Insight into the relationship between resting heart rate and atrial fibrillation: a Mendelian randomization study

Abstract Aims A low resting heart rate (RHR) implies a more efficient heart function and a lower risk of cardiovascular disease. However, observational studies have reported a U-shaped association between RHR and atrial fibrillation (AF). In contrast, Mendelian randomization (MR) studies have found an inverse causal association between RHR and AF. Hence, the causal nature of the relationship is not clear. The aim is to investigate the causal association and its shape between RHR on AF using linear and non-linear MR (NLMR). Methods and results Linear and non-linear MR were performed on individual-level data in the Trøndelag Health Study (HUNT) and UK Biobank (UKB). HUNT consists of 69 155 individuals with 7,062 AF cases, while UKB provides data on 431 852 individuals with 20 452 AF cases. The linear MR found an inverse relationship between RHR and AF with an OR = 0.95 [95% confidence interval (CI): 0.93–0.98] and OR = 0.96 (95% CI: 0.95–0.97) per unit decrease in RHR in HUNT and UKB, respectively. The NLMR was supportive of an inverse linear relationship in both HUNT and UKB for RHR values <90 beats per minute (bpm). Several sensitivity analyses were also consistent. Conclusion In contrast with the current observational knowledge of RHR and AF, an inverse causal association between RHR and AF was demonstrated in both linear and non-linear MR for RHR values up to 90 bpm. Further exploring the underlying mechanisms of the genetic instrument for RHR may shed light on whether pleiotropy is biasing this association.
Epigenetic reprogramming of a distal developmental enhancer cluster drives SOX2 overexpression in breast and lung adenocarcinoma

Abstract Enhancer reprogramming has been proposed as a key source of transcriptional dysregulation during tumorigenesis, but the molecular mechanisms underlying this process remain unclear. Here, we identify an enhancer cluster required for normal development that is aberrantly activated in breast and lung adenocarcinoma. Deletion of the SRR124–134 cluster disrupts expression of the SOX2 oncogene, dysregulates genome-wide transcription and chromatin accessibility and reduces the ability of cancer cells to form colonies in vitro. Analysis of primary tumors reveals a correlation between chromatin accessibility at this cluster and SOX2 overexpression in breast and lung cancer patients. We demonstrate that FOXA1 is an activator and NFIB is a repressor of SRR124–134 activity and SOX2 transcription in cancer cells, revealing a co-opting of the regulatory mechanisms involved in early development. Notably, we show that the conserved SRR124 and SRR134 regions are essential during mouse development, where homozygous deletion results in the lethal failure of esophageal–tracheal separation. These findings provide insights into how developmental enhancers can be reprogrammed during tumorigenesis and underscore the importance of understanding enhancer dynamics during development and disease.
Improvement in male pelvis magnetic resonance image contouring following radiologist‐delivered training

Abstract Introduction The magnetic resonance linear accelerator (MRL) combines both magnetic resonance imaging and a linear accelerator, allowing for daily treatment adaptation. This study aimed to assess the impact of radiologist‐delivered training in magnetic resonance (MR) contouring of relevant structures within the male pelvis. Methods Two radiation oncologists, two radiation oncology registrars and seven radiation therapists completed contouring on 10 male pelvis MR datasets both pre‐ and post‐training. A 2‐hour MR anatomy training session was delivered by a radiologist, who also provided the ‘gold standard’ contours. The pre‐ and post‐training contours were compared against the gold standard with Dice similarity coefficient (DSC) and Hausdorff distances calculated; and the pre‐ and post‐confidence scores and timing were compared. Results The improvement in DSC were significant in prostate, rectum and seminal vesicles, with a post‐training median DSC of 0.87 ± 0.06, 0.92 ± 0.04 and 0.80 ± 0.14, respectively. The median Hausdorff improved with a median of 1.46 ± 0.78 mm, 0.52 ± 0.32 mm and 1.11 ± 0.86 mm for prostate, rectum and seminal vesicles, respectively. Bladder concordance was high both pre‐ and post‐training. Urethra contours improved post‐training, however, remained difficult to contour with a median post‐DSC of 0.51 ± 0.24. Overall, confidence scoring improved (P < 0.001) and timing decreased by an average of 4.4 ± 16.4 min post‐training. Conclusion Radiologist‐delivered training improved concordance of male pelvis contouring on MR datasets. Further work is required in the identification of urethra on MRs. These findings are of importance in the MRL adaptive workflow.
Synchrotron X-rays reveal the modes of Fe binding and trace metal storage in the brown algae Laminaria digitata and Ectocarpus siliculosus

Abstract Iron is accumulated symplastically in kelp in a non-ferritin core that seems to be a general feature of brown algae. Microprobe studies show that Fe binding depends on tissue type. The sea is generally an iron-poor environment and brown algae were recognized in recent years for having a unique, ferritin-free iron storage system. Kelp (Laminaria digitata) and the filamentous brown alga Ectocarpus siliculosus were investigated using X-ray microprobe imaging and nanoprobe X-ray fluorescence tomography to explore the localization of iron, arsenic, strontium, and zinc, and micro-X-ray absorption near-edge structure (μXANES) to study Fe binding. Fe distribution in frozen hydrated environmental samples of both algae shows higher accumulation in the cortex with symplastic subcellular localization. This should be seen in the context of recent ultrastructural insight by cryofixation–freeze substitution that found a new type of cisternae that may have a storage function but differs from the apoplastic Fe accumulation found by conventional chemical fixation. Zn distribution co-localizes with Fe in E. siliculosus, whereas it is chiefly located in the L. digitata medulla, which is similar to As and Sr. Both As and Sr are mostly found at the cell wall of both algae. XANES spectra indicate that Fe in L. digitata is stored in a mineral non-ferritin core, due to the lack of ferritin-encoding genes. We show that the L. digitata cortex contains mostly a ferritin-like mineral, while the meristoderm may include an additional component.
Prioritization of clinical questions for the Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis

Living guidelines aim to reduce delays in translating new knowledge into practice by updating individual recommendations as soon as relevant new evidence emerges. We surveyed members of the Australian Rheumatology Association (ARA) to develop a list of priority questions for the Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis (ALG) and to explore clinicians' use of clinical practice guidelines.
Risk factors for post-acute sequelae of COVID-19 in hospitalized patients: An observational study based on a survey in a tertiary care center in Türkiye

ABSTRACT Risk factors for post-acute sequelae of COVID-19 in hospitalized patients: An observational study based on a survey in a tertiary care center in Türkiye Introduction Long COVID is a multisystem disease with various symptoms and risk factors. We aim to investigate the post-acute sequelae of COVID-19 and related risk factors in a tertiary care center. Materials and Methods In this observational study, based on a survey of 1.977 COVID-19 patients hospitalized from April 2020 to January 2021, a retrospective assessment was carried out on 1.050 individuals who were reachable via telephone to determine their eligibility for meeting the inclusion criteria. Results The data of 256 patients who reported at least one persistent symptom were analyzed. Long COVID prevalence was 24.3%. Among 256 patients (median age 52.8; 52.7% female; 56.63% had at least one comorbidity), dyspnea, fatigue, arthralgia-myalgia, cough, and back pain were the most common post-acute sequelae of COVID-19 (42.4%; 28.29%; 16.33%; 13.15% and 7.17%, respectively). The risk factors for the persistence of dyspnea included having lung diseases such as chronic obstructive pulmonary disease, a history of intensive care support, the requirement for long-term oxygen therapy, and a history of cytokine storm (p= 0.024, p= 0.026, p< 0.001, p= 0.036, p= 0.005, respectively). The correlation between lung involvement with post-discharge cough (p= 0.041) and dizziness (p= 0.038) was significant. No correlation between the symptoms with the severity of acute infection, age, and gender was found. When a multivariate regression analysis was conducted on the most common long COVID-related symptoms, several independent risk factors were identified. These included having lung disease for dyspnea (OR 5.81, 95% CI 1.08-31.07, p= 0.04); length of hospital stay for myalgia (OR 1.034, 95% CI 1.004-1.065, p= 0.024); and pulmonary involvement of over 50% during COVID-19 infection for cough (OR 3.793, 95% CI 1.184-12.147, p= 0.025). Conclusion COVID-19 survivors will require significant healthcare services due to their prolonged symptoms. We hope that our findings will guide the management of these patients in clinical settings towards best practices.
Ventilatory effects of fentanyl, heroin, and d -methamphetamine , alone and in mixtures, in male rats breathing normal air.

The number of drug overdoses and deaths has increased significantly over the past decade and co-use of opioids and stimulants is associated with greater likelihood of overdose and decreased likelihood of accessing treatment, compared with use of opioids alone. Potential adverse effects of opioid/stimulant mixtures, particularly methamphetamine, are not well characterized. Two structurally different drugs with agonist properties at µ-opioid receptors (MOR), fentanyl and heroin, and d-methamphetamine, alone and in mixtures, were assessed for their effects on ventilation in rats breathing normal air. Whole-body phethysmography chambers were equipped with a tower and swivel allowing infusions to indwelling intravenous (i.v.) catheters. After a 45-minute habituation period, saline, fentanyl, heroin, or d-methamphetamine, alone and in mixtures, was administered. Five minutes the opioid receptor antagonist naloxone or vehicle was injected. Fentanyl (0.0032-0.1 mg/kg) and heroin (0.32-3.2 mg/kg) decreased ventilation [frequency (f) and tidal volume (VT)] in a dose-related manner whereas d-methamphetamine (0.1-3.2 mg/kg) increased f to >400% of control and decreased VT to <60% of control, overall increasing minute volume (product of f and VT) to >240% of control. When combined, d-methamphetamine (0.1-3.2 mg/kg) attenuated the ventilatory depressant effects of fentanyl (0.1 mg/kg) and heroin (3.2 mg/kg). d-Methamphetamine did not alter the potency of naloxone to reverse the ventilatory depressant effects of fentanyl or heroin. These studies demonstrate that d-methamphetamine can attenuate the ventilatory depressant effects of moderate doses of opioid receptor agonists while not altering the potency of naloxone to reverse opioid hypoventilation. Significance Statement Co-use of opioids and stimulants is associated with greater likelihood of overdose and decreased likelihood of accessing treatment, compared with use of opioids alone. Potential adverse effects of opioid/stimulant mixtures are not well characterized. This study reports that 1) d-methamphetamine attenuates the ventilatory depressant effects of moderate doses of two structurally different µ-opioid receptor agonists, fentanyl and heroin, and 2) d-methamphetamine does not alter potency or effectiveness of naloxone to reverse the ventilatory depressant effects of the opioid receptor agonists.
Immune Monitoring-Guided Versus Fixed Duration of Antiviral Prophylaxis Against Cytomegalovirus in Solid-Organ Transplant Recipients: A Multicenter, Randomized Clinical Trial

Abstract Background The use of assays detecting cytomegalovirus (CMV)–specific T cell–mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. Methods In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus. Results Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, −0.1; 95% confidence interval [CI], −13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, −26.0 days; 95%, CI, −41.1 to −10.8 days; P < .001). Conclusions Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection. Clinical Trials Registration NCT02538172.
A JROD survey: nationwide overview of radiotherapy data from 2015 to 2021

Abstract The purpose of this survey was to examine the status of radiotherapy in Japan based on the cases registered in the Japanese Radiation Oncology Database (JROD), from 2015 to 2021, and to provide basic data to help improve the usefulness of the JROD in the future. The study population consisted of patients who underwent radiotherapy between 2014 and 2020 and did not opt out of the study. The survey item data analyzed in this study were entered into the database at each radiotherapy institution by referring to medical records from the preceding year. Our results show that the number of registered radiotherapy institutions and cases increased by ~50% in 2019 compared to those in 2015 (to 113 institutions and 60 575 cases, respectively). Among the survey item categories, the registration rate was lowest for prognostic information (13.9% on average over the 7-year period). In terms of the Japanese Society for Radiation Oncology disease site, the breast; lung, trachea and mediastinum and urogenital sites accounted for >50% of the total cases. The average survival and mortality rates over the 7-year study period were 67.4 and 17.4%, respectively. The X-ray radiotherapy completion rate exceeded 90% for all years and across all disease categories. 192Ir-based brachytherapy and 223Ra-based radionuclide therapy accounted for an average of 61.9 and 44.6%, respectively, of all corresponding cases over the 7-year period. In conclusion, this survey enables us to infer the actual status of radiotherapy in Japan based on the analysis of relevant nationwide data.
Extracorporeal Life Support for Patients With Newly Diagnosed HIV and Acute Respiratory Distress Syndrome: A Systematic Review and Analysis of Individual Patient Data

Extracorporeal membrane oxygenation (ECMO) may improve survival in patients with severe acute respiratory distress syndrome (ARDS). However, presence of immunosuppression is a relative contraindication for ECMO, which is withheld in HIV patients. We performed a systematic review to investigate the outcome of newly diagnosed HIV patients with ARDS receiving ECMO support. Our search yielded 288 publications, with 22 studies finally included. Initial presentation included fever, respiratory distress, and cough. Severe immunodeficiency was confirmed in most patients. Deceased patients had a higher viral load, a lower Horovitz index, and antiretroviral therapy utilized before ECMO. Moreover, ECMO duration was longer (p = 0.0134), and all deceased suffered from sepsis (p = 0.0191). Finally, despite the development of therapeutic options for HIV patients, ECMO remains a relative contraindication. We found that ECMO may successfully bridge the time for pulmonary recovery in 93% of patients, with a very good outcome. Using ECMO, the time for antimicrobial therapy, lung-protective ventilation, and immune system restitution may be gained. Further studies clarifying the role of ECMO in HIV are crucial and until these data are available, ECMO might be appropriate in immunocompromised patients. This holds especially true in newly diagnosed HIV patients, who are usually young, without comorbidities, with a good rehabilitation potential.
Effect of Heat Treatment Temperature on the Color of Okan Wood

In this study the effect of high temperature on color change of okan wood was investigated. Wood specimens were subjected to heat treatment at 160°C, 180°C,200°C,220°Cfor 4 hours with the superheated steam as a heating medium and a shielding gas. Color changes were measured in the Minolta Croma-Meter CR-300 color system. The color parameters L*, a*, b* were determined by the CIEL*a*b* method on the surface of untreated and treated wood, and their variation with regard to the treatment (△L*,△a*,△b* ) were calculated. It was found that heat treatment resulted in a darkening of wood tissues, Color became dark with the temperature increases. The darkening accelerated when treatment temperature exceeded approximately 200°C. We found that heat treatment temperature were substantially important regarding the color responses. Strong correlations between total color difference and the treatment temperature were found. The effect of treatment temperature on color change in sapwood is more obvious than that in heartwood, the color of sapwood and heartwood tended to be more uniform when the temperature reaches more than 200°C.
Total-body Dynamic Imaging and Kinetic Modeling of 18F-AraG in Healthy Individuals and a Non-Small Cell Lung Cancer Patient Undergoing Anti-PD-1 Immunotherapy

Immunotherapies, especially the checkpoint inhibitors such as anti-PD-1 antibodies, have transformed cancer treatment by enhancing immune system's capability to target and kill cancer cells. However, predicting immunotherapy response remains challenging. 18F-AraG is a molecular imaging tracer targeting activated T cells, which may facilitate therapy response assessment by non-invasive quantification of immune cell activity within tumor microenvironment and elsewhere in the body. The aim of this study was to obtain preliminary data on total-body pharmacokinetics of 18F-AraG, as a potential quantitative biomarker for immune response evaluation. Methods: The study consisted of 90-min total-body dynamic scans of four healthy subjects and one non-small cell lung cancer (NSCLC) patient, scanned before and after anti-PD-1 immunotherapy. Compartmental modeling with Akaike information criterion model selection were employed to analyze tracer kinetics in various organs. Additionally, seven sub-regions of the primary lung tumor and four mediastinal lymph nodes were analyzed. Practical identifiability analysis was performed to assess reliability of kinetic parameter estimation. Correlations of SUVmean, SUVR (tissue-to-blood ratio), and Logan plot slope (K_Logan) with total volume-of-distribution (V_T) were calculated to identify potential surrogates for kinetic modeling. Results: Strong correlations were observed between K_Logan and SUVR values with V_T, suggesting that they can be used as promising surrogates for V_T, especially in organs with low blood-volume fraction. Moreover, the practical identifiability analysis suggests that the dynamic 18F-AraG PET scans could potentially be shortened to 60 minutes, while maintaining quantification accuracy for all organs-of-interest. The study suggests that although 18F-AraG SUV images can provide insights on immune cell distribution, kinetic modeling or graphical analysis methods may be required for accurate quantification of immune response post-therapy. While SUVmean showed variable changes in different sub-regions of the tumor post-therapy, the SUVR, K_Logan, and V_T showed consistent increasing trends in all analyzed sub-regions of the tumor with high practical identifiability. Conclusion: Our findings highlight the promise of 18F-AraG dynamic imaging as a non-invasive biomarker for quantifying the immune response to immunotherapy in cancer patients. The promising total-body kinetic modeling results also suggest potentially wider applications of the tracer in investigating the role of T cells in the immunopathogenesis of diseases.
Early Detection of Bark Beetle Atack Using Remote Sensing and Machine Learning

Bark beetle outbreaks can have serious consequences on forest ecosystem processes, biodiversity, forest structure and function, and economies. Thus, accurate and timely detection of bark beetle infestations in the early stage (known as green-attack detection) is crucial to mitigate the further impact, develop proactive forest management activities, and minimize economic losses. Incorporating remote sensing (RS) data with machine learning (ML) (or deep learning (DL)) can provide a great alternative to the current approaches that primarily rely on aerial surveys and ield surveys, which can be impractical over vast areas. Existing approaches that exploit RS and ML/DL exhibit substantial diversity due to the wide range of factors involved. This paper provides a comprehensive review of past and current advances in green-attack detection from three primary perspectives: bark beetle & host interactions, RS, and ML/DL. In contrast to prior eforts, this review encompasses all RS systems and emphasizes ML/DL methods to investigate their strengths and weaknesses. We parse existing literature based on multi-or hyper-spectral analyses and distill their knowledge based on: bark beetle species & attack phases with a primary emphasis on early stages of attacks, host trees, study regions, RS platforms & sensors, spectral/spatial/temporal resolutions, spectral signatures, spectral vegetation indices, ML approaches, learning schemes, task categories, models, algorithms, classes/clusters, features, and DL networks & architectures. Although DL-based methods and the random forest algorithm showed promising results, highlighting their potential to detect subtle changes across visible, thermal, and short-wave infrared spectral regions, their efectiveness remains limited, and high uncertainties persist due to the subtle distinctions between healthy and attacked trees. To inspire novel solutions to these shortcomings, we delve into the principal challenges & opportunities from diferent perspectives, enabling a deeper understanding of the current state of research and guiding future research directions.