Miracle-dz/UniFAR-FTUs huggingface dataset:
Empagliflozin Treatment Is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes

Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of major adverse cardiovascular (CV) events and hospitalization for heart failure (HF) in patients with type 2 diabetes (T2D). Using CV MRI (CMR) and 31P-MRS in a longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2 inhibitor empagliflozin on myocardial energetics and cellular volume, function, and perfusion. Eighteen patients with T2D underwent CMR and 31P-MRS scans before and after 12 weeks’ empagliflozin treatment. Plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) levels were measured. Ten volunteers with normal glycemic control underwent an identical scan protocol at a single visit. Empagliflozin treatment was associated with significant improvements in phosphocreatine-to-ATP ratio (1.52 to 1.76, P = 0.009). This was accompanied by a 7% absolute increase in the mean left ventricular ejection fraction (P = 0.001), 3% absolute increase in the mean global longitudinal strain (P = 0.01), 8 mL/m2 absolute reduction in the mean myocardial cell volume (P = 0.04), and 61% relative reduction in the mean NT-proBNP (P = 0.05) from baseline measurements. No significant change in myocardial blood flow or diastolic strain was detected. Empagliflozin thus ameliorates the “cardiac energy-deficient” state, regresses adverse myocardial cellular remodeling, and improves cardiac function, offering therapeutic opportunities to prevent or modulate HF in T2D.
Open-source Longitudinal Sleep Analysis From Accelerometer Data (DPSleep): Algorithm Development and Validation

Background Wearable devices are now widely available to collect continuous objective behavioral data from individuals and to measure sleep. Objective This study aims to introduce a pipeline to infer sleep onset, duration, and quality from raw accelerometer data and then quantify the relationships between derived sleep metrics and other variables of interest. Methods The pipeline released here for the deep phenotyping of sleep, as the DPSleep software package, uses a stepwise algorithm to detect missing data; within-individual, minute-based, spectral power percentiles of activity; and iterative, forward-and-backward–sliding windows to estimate the major Sleep Episode onset and offset. Software modules allow for manual quality control adjustment of the derived sleep features and correction for time zone changes. In this paper, we have illustrated the pipeline with data from participants studied for more than 200 days each. Results Actigraphy-based measures of sleep duration were associated with self-reported sleep quality ratings. Simultaneous measures of smartphone use and GPS location data support the validity of the sleep timing inferences and reveal how phone measures of sleep timing can differ from actigraphy data. Conclusions We discuss the use of DPSleep in relation to other available sleep estimation approaches and provide example use cases that include multi-dimensional, deep longitudinal phenotyping, extended measurement of dynamics associated with mental illness, and the possibility of combining wearable actigraphy and personal electronic device data (eg, smartphones and tablets) to measure individual differences across a wide range of behavioral variations in health and disease. A new open-source pipeline for deep phenotyping of sleep, DPSleep, analyzes raw accelerometer data from wearable devices and estimates sleep onset and offset while allowing for manual quality control adjustments.
Intensified antiplatelet therapy in patients after percutaneous coronary intervention with high on‐treatment platelet reactivity: the OPTImal Management of Antithrombotic Agents (OPTIMA)‐2 Trial

High on‐treatment platelet reactivity (HOPR) is associated with increased risk of cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). We randomised post‐PCI patients with HOPR after 5 days of standard dual antiplatelet therapy (DAPT) to intensified therapy with aspirin 100 mg once daily in combination with either clopidogrel 150 mg once daily, clopidogrel 75 mg once daily plus cilostazol 100 mg twice daily, ticagrelor 90 mg twice daily, or standard therapy with clopidogrel 75 mg once daily (STD) for 1 month, after which all patients were switched to standard DAPT for a further 11 months. The primary outcome was residual HOPR rate at 1 month. We screened 1724 patients with light transmission aggregation studies and randomised 434 with HOPR. At 1 month the proportion of patients with persistent HOPR was significantly lower in the intensified therapy groups compared with STD group. Compared to the group receiving STD therapy, those receiving intensified therapy had significantly lower rate of major adverse cardiovascular events (MACE) at both 1 month and 12 months with no significant increase in bleeding. In patients with post‐PCI HOPR, 1 month of intensified antiplatelet therapy provides greater platelet inhibition and improves outcomes without increasing bleeding.
A plant-pollinator metanetwork along a habitat fragmentation gradient.

To understand how plant-pollinator interactions respond to habitat fragmentation, we need novel approaches that can capture properties that emerge at broad scales, where multiple communities engage in metanetworks. Here we studied plant-pollinator interactions over 2 years on 29 calcareous grassland fragments selected along independent gradients of habitat size and surrounding landscape diversity of cover types. We associated network centrality of plant-pollinator interactions and grassland fragments with their ecological and landscape traits, respectively. Interactions involving habitat specialist plants and large-bodied pollinators were the most central, implying that species with these traits form the metanetwork core. Large fragments embedded in landscapes with high land cover diversity exhibited the highest centrality; however, small fragments harboured many unique interactions not found on larger fragments. Intensively managed landscapes have reached a point in which all remaining fragments matter, meaning that losing any further areas may vanish unique interactions with unknown consequences for ecosystem functioning.
PDGF as an Important Initiator for Neurite Outgrowth Associated with Fibrovascular Membranes in Proliferative Diabetic Retinopathy

ABSTRACT Purpose The formation of fibrovascular membranes (FVMs) is a serious sight-threatening complication of proliferative diabetic retinopathy (PDR) that may result in retinal detachment and eventual blindness. During the formation of these membranes, neurite/process outgrowth occurs in retinal neurons and glial cells, which may both serve as a scaffold and have guiding or regulatory roles. To further understand this process, we investigated whether previously identified candidate proteins, from vitreous of PDR patients with FVMs, could induce neurite outgrowth in an experimental setting. Materials and methods Retinal explants of C57BL6/N mouse pups on postnatal day 3 (P3) were cultured in poly-L-lysine- and laminin-coated dishes. Outgrowth stimulation experiments were performed with the addition of potential inducers of neurite outgrowth. Automated analysis of neurite outgrowth was performed by measuring β–tubulin-immunopositive neurites using Image J. Expression of PDGF receptors was quantified by RT-PCR in FVMs of PDR patients. Results Platelet-derived growth factor (PDGF) induced neurite outgrowth in a concentration-dependent manner, whilst neuregulin 1 (NRG1) and connective tissue growth factor (CTGF) did not. When comparing three different PDGF dimers, treatment with PDGF-AB resulted in the highest neurite induction, followed by PDGF-AA and -BB. In addition, incubation of retinal explants with vitreous from PDR patients resulted in a significant induction of neurite outgrowth as compared to non-diabetic control vitreous from patients with macular holes, which could be prevented by addition of CP673451, a potent PDGF receptor (PDGFR) inhibitor. Abundant expression of PDGF receptors was detected in FVMs. Conclusion Our findings suggest that PDGF may be involved in the retinal neurite outgrowth, which is associated with the formation of FVMs in PDR.
Structure-Composition-Property Relationships in Antiperovskite Nitrides: Guiding a Rational Alloy Design.

The alloy strategy through the A- or X-site is a common method for experimental preparation of high-performance and stable lead-based perovskite solar cells. As one of the important candidates for lead-free and stable photovoltaic absorbers, the inorganic antiperovskite family has recently been reported to exhibit excellent optoelectronic properties. However, the current reports on the design of antiperovskite alloys are rare. In this work, we investigated the previously overlooked electronic property (e.g., conduction band convergence), static dielectric constant, and exciton binding energy in inorganic antiperovskite nitrides by first-principles calculations. Then, we revealed a linear relationship between the tolerance factor and various physical quantities. Guided by the established structure-composition-property relationship in six antiperovskite nitrides X3NA (X2+ = Mg2+, Ca2+, Sr2+; A3- = P3-, As3-, Sb3-, Bi3-), for the first time, we designed a promising antiperovskite alloy Mg3NAs0.5Bi0. 5 with a quasi-direct band gap of 1.402 eV. Finally, we made a comprehensive comparison between antiperovskite nitrides and conventional halide perovskites for pointing out the future direction for device applications.
Voluntary alcohol binge‐drinking in adolescent C57Bl6 mice induces delayed appearance of behavioural defects in both males and females

Adolescence is a developmental period characterized by significant changes in brain architecture and behaviour. The immaturity of the adolescent brain is associated with heightened vulnerability to exogenous agents, including alcohol. Alcohol is the most consumed drug among teenagers, and binge‐drinking during adolescence is a major public health concern. Studies have suggested that adolescent alcohol exposure may interfere with the maturation of frontal brain regions and lead to long‐lasting behavioural consequences. In this study, by using a slightly modified version of the Drinking in the Dark paradigm, adolescent C57Bl6 mice reach high blood alcohol concentration after voluntary binge‐drinking. In order to assess short‐ and long‐term consequences of adolescent alcohol exposure (AAE), a battery of behavioural tests was performed during late adolescence and during adulthood. We showed that AAE had no short‐term effect on young mice behaviour but rather increased anxiety‐ and depressive‐like behaviours, as well as alcohol consumption during adulthood. Moreover, alcohol binge‐drinking during adolescence dramatically decreased recognition memory performances and behavioural flexibility in both adult males and females. Furthermore, we showed that voluntary consumption of alcohol during adolescence did not trigger any major activation of the innate immune system in the prefrontal cortex. Together, our data suggest that voluntary alcohol binge‐drinking in adolescent mice induces a delayed appearance of behavioural impairments in adulthood.
Diagnostic Key Points and Surgical Management of Necrotizing Fasciitis: A Retrospective Study

Necrotizing fasciitis (NF) is a fatal disease with a high mortality rate that can be easily misdiagnosed. The aim of this study was to improve the diagnostic rate of NF and overall survival. We conducted a single-center, retrospective, noncontrolled study involving 36 patients who were admitted to our department between December 2017 and October 2019, and summarized the diagnostic key points and timing of surgical treatment. All patients were diagnosed at our department and underwent multiple courses of treatment. The records included information regarding underlying diseases, bacterial culture results, laboratory risk indicator for necrotizing fasciitis (LRINEC) score, number of procedures, and type of antibiotics. All 36 cases of NF were cured and showed good patient condition on follow-up; the mean number of surgeries was three, and the mean duration of hospitalization was 37 days (range, 21-83 days). The LRINEC scores of 16 patients were ≥8 points. Seventeen patients with underlying diabetic disease had higher inflammatory index scores than those without diabetes. The LRINEC scores of patients with (n = 17) and without (n = 19) DM were 7.40 ± 2.99 and 3.80 ± 2.39, respectively (P < .01). Cases of NF that were treated with early incision and surgical abscess drainage required fewer surgeries and a shorter length of hospitalization. Thus, surgeons should be more aware of NF and aim to make an early and accurate diagnosis using various approaches. Complete surgical debridement plays an essential role in NF treatment, and diabetes mellitus is a significant adverse factor that exacerbates the severity of NF. Negative-pressure techniques are useful in cases involving nonanaerobic infections and cause minimal complications.
Smoking Protective and Risk Factors Among Transgender and Gender-Expansive Individuals (Project SPRING): Qualitative Study Using Digital Photovoice

Background Transgender and gender-expansive (TGE) adults are twice as likely to smoke cigarettes than cisgender individuals. There is a critical gap in research on effective and culturally sensitive approaches to reduce smoking prevalence among TGE adults. Objective This study aims to qualitatively examine the risk and protective factors of cigarette smoking among TGE adults through real-world exemplars. Methods We conducted a digital photovoice study among a purposeful sample of 47 TGE adults aged ≥18 years and currently smoking in the United States (March 2019-April 2020). Participants uploaded photos daily that depicted smoking risk and protective factors they experienced over 21 days on either private Facebook or Instagram groups. Next, we conducted separate focus group discussions to explore the experiences of these factors among a subset of participants from each group. We analyzed participants’ photos, captions, and focus group transcripts and generated themes associated with smoking risk and protective factors. Results We identified 6 major themes of risk and protective factors of smoking among TGE individuals: experience of stress, gender affirmation, health consciousness, social influences, routine behaviors, and environmental cues. We describe and illustrate each theme using exemplar photos and quotes. Conclusions The findings of this study will inform future community-engaged research to develop culturally tailored interventions to reduce smoking prevalence among TGE individuals.
Pharmacological and non-pharmacological treatments for restless legs syndrome in end-stage kidney disease: a systematic review and component network meta-analysis

ABSTRACT Background Restless legs syndrome (RLS) is common among patients with end-stage kidney disease (ESKD) and is associated with poor outcomes. Several recently published studies had focused on pharmacological and non-pharmacological treatments of RLS, but an updated meta-analysis has not been conducted. Methods The study population was adult ESKD patients on dialysis with RLS. Randomized controlled trials (RCTs) were selected. The primary outcome was reduction in RLS severity. The secondary outcomes were improvement in sleep quality and treatment-related adverse events. Frequentist standard network meta-analysis (NMA) and additive component NMA were performed. The evidence certainty was assessed using the Confidence in NMA (CINeMA) framework. Results A total of 24 RCTs with 1252 participants were enrolled and 14 interventions were compared. Cool dialysate produced the largest RLS severity score reduction {mean difference [MD] 16.82 [95% confidence interval (CI) 10.635–23.02]} and a high level of confidence. Other potential non-pharmacological interventions include intradialytic stretching exercise [MD 12.00 (95% CI 7.04–16.97)] and aromatherapy massage [MD 10.91 (95% CI 6.96–14.85)], but all with limited confidence of evidence. Among the pharmacological interventions, gabapentin was the most effective [MD 8.95 (95% CI 1.95–15.85)], which also improved sleep quality [standardized MD 2.00 (95% CI 0.47–3.53)]. No statically significant adverse events were detected. Conclusions The NMA supports that cool dialysate is appropriate to treat patients with ESKD and RLS. Gabapentin is the most effective pharmacological intervention and also might improve sleep quality. Further parallel RCTs with sufficient sample sizes are required to evaluate these potential interventions and long-term effects.
The management of post-transplantation recurrence of hepatocellular carcinoma

The annual incidence of hepatocellular carcinoma (HCC) continues to rise. Over the last two decades, liver transplantation (LT) has become the preferable treatment of HCC, when feasible and strict selection criteria are met. With the rise in HCC-related LT, compounded by downstaging techniques and expansion of transplant selection criteria, a parallel increase in number of post-transplantation HCC recurrence is expected. Additionally, in the context of an immunosuppressed transplant host, recurrences may behave aggressively and more challenging to manage, resulting in poor prognosis. Despite this, no consensus or best practice guidelines for post-transplantation cancer surveillance and recurrence management for HCC currently exist. Studies with adequate population sizes and high-level evidence are lacking, and the role of systemic and locoregional therapies for graft and extrahepatic recurrences remains under debate. This review seeks to summarize the existing literature on post-transplant HCC surveillance and recurrence management. It highlights the value of early tumour detection, re-evaluating the immunosuppression regimen, and staging to differentiate disseminated recurrence from intrahepatic or extrahepatic oligo-recurrence. This ultimately guides decision-making and maximizes treatment effect. Treatment recommendations specific to recurrence type are provided based on currently available locoregional and systemic therapies.
Bispecific antibodies for the treatment in inflammatory bowel disease: an avenue worth exploring?

Department of Gastroenterology and Inserm NGERE U1256, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France; Ingénierie Moléculaire et Ingénierie Articulaire (IMoPA), UMR-7365 CNRS, Faculté de Médecine, University of Lorraine and University Hospital of Nancy, Vandoeuvre-lès-Nancy, France; Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele Milano, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele Milano, Italy
Genomic and Transcriptomic Analysis of Relapsed and Refractory Childhood Solid Tumors Reveals a Diverse Molecular Landscape and Mechanisms of Immune Evasion

Tumor heterogeneity, chemotherapy exposure, and tumor evolution contribute to the molecular profiles and increased mutational burden that occur in treatment-refractory and relapsed childhood solid tumors. Children with treatment-refractory or relapsed (R/R) tumors face poor prognoses. As the genomic underpinnings driving R/R disease are not well defined, we describe here the genomic and transcriptomic landscapes of R/R solid tumors from 202 patients enrolled in Beat Childhood Cancer Consortium clinical trials. Tumor mutational burden (TMB) was elevated relative to untreated tumors at diagnosis, with one-third of tumors classified as having a pediatric high TMB. Prior chemotherapy exposure influenced the mutational landscape of these R/R tumors, with more than 40% of tumors demonstrating mutational signatures associated with platinum or temozolomide chemotherapy and two tumors showing treatment-associated hypermutation. Immunogenomic profiling found a heterogenous pattern of neoantigen and MHC class I expression and a general absence of immune infiltration. Transcriptional analysis and functional gene set enrichment analysis identified cross-pathology clusters associated with development, immune signaling, and cellular signaling pathways. While the landscapes of these R/R tumors reflected those of their corresponding untreated tumors at diagnosis, important exceptions were observed, suggestive of tumor evolution, treatment resistance mechanisms, and mutagenic etiologies of treatment. Significance: Tumor heterogeneity, chemotherapy exposure, and tumor evolution contribute to the molecular profiles and increased mutational burden that occur in treatment-refractory and relapsed childhood solid tumors.
Nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex - disease burden, unmet needs, and advances in treatment developments

ABSTRACT Introduction Nontuberculous mycobacterial (NTM) lung disease (LD) is the most common clinical manifestation of NTM infection and is a growing health concern. Up to 85% of NTM-LD cases are caused by Mycobacterium avium complex (MAC). Increased awareness of NTM-LD caused by MAC is needed as patients with this disease experience substantial burden and unmet treatment needs. Areas covered This review provides clinicians and regulatory and healthcare decision makers an overview of the clinical, economic, and humanistic burden of NTM-LD and the unmet treatment needs faced by patients and clinicians. The review focuses on NTM-LD caused by MAC. A summary of the 2020 NTM guidelines specifically for MAC-LD and an overview of novel treatment options, including amikacin liposome inhalation suspension (ALIS) as the first approved therapy for refractory MAC-LD, and investigational drugs in testing phase are provided. Expert opinion Key advancements in NTM-LD management include recent updates to clinical practice guidelines, approval of ALIS for the treatment of refractory MAC-LD, and ongoing clinical trials of investigational treatments. Yet opportunities still exist to improve patient outcomes, including development of better screening tools, such as reliable and responsive biomarkers to help identify high-risk patients, and addressing unmet treatment needs.
Using Narrow Band CE-Chirps to Elicit Cervical Vestibular Evoked Myogenic Potentials

Objectives: To compare the effects of Narrow band CE-Chirps (NB CE-Chirps) and tone bursts (TBs) at 500 Hz and 1000 Hz on the amplitudes and latencies in cervical vestibular evoked myogenic potentials (cVEMPs). Design: Thirty-one healthy adult volunteers of varying ages were tested by air conduction at 95 dB nHL. Recording conditions were randomized for each participant and each modality was tested twice. Results: NB CE-Chirps showed larger corrected amplitudes than TBs at 500 Hz (p < 0.001) which were themselves larger than NB CE-Chirps and TBs at 1000 Hz (p < 0.001). In older volunteers, NB CE-Chirps 500 and 1000 Hz had significantly higher response rates than TBs 500 Hz (p = 0.039). A negative correlation was observed between the corrected amplitudes and the age of the participants regardless of the stimulus and the frequency studied. The p13 and n23 latencies were not correlated with the age of the subjects. Conclusions: NB CE-Chirps at 500 Hz improved the corrected amplitudes of waveforms in cVEMPs as a result of a better frequency specificity compared with TBs. In the elderly, eliciting cVEMPs at a frequency of 1000 Hz might not be necessary to improve response rates with NB CE-Chirps. Additional studies including a higher number of healthy participants and patients with vestibular disorders are required to confirm these observations.