Miracle-dz/UniFAR-FTUs huggingface dataset:
Microglia regulate chandelier cell axo-axonic synaptogenesis

Significance Chandelier cells (ChCs) are a unique type of GABAergic interneuron that form axo-axonic synapses exclusively on the axon initial segment (AIS) of neocortical pyramidal neurons (PyNs), allowing them to exert powerful yet precise control over PyN firing and population output. The importance of proper ChC function is further underscored by the association of ChC connectivity defects with various neurological conditions. Despite this, the cellular mechanisms governing ChC axo-axonic synapse formation remain poorly understood. Here, we identify microglia as key regulators of ChC axonal morphogenesis and AIS synaptogenesis, and show that disease-induced aberrant microglial activation perturbs proper ChC synaptic development/connectivity in the neocortex. In doing so, such findings highlight the therapeutic potential of manipulating microglia to ensure proper brain wiring.
Efficacy of capacitive resistive monopolar radiofrequency in the physiotherapeutic treatment of chronic pelvic pain syndrome: A randomized controlled trial

To evaluate the efficacy of adjuvant, capacitive resistive monopolar radiofrequency (CRMRF, INDIBA) treatment at 448 kHz together with physiotherapeutic techniques compared to a sham treatment with the same techniques, for pain reduction and quality of life (QoL) improvements in patients with chronic pelvic pain syndrome (CPPS).
A Late Paleocene age for Greenland’s Hiawatha impact structure

The ~31-km-wide Hiawatha structure, located beneath Hiawatha Glacier in northwestern Greenland, has been proposed as an impact structure that may have formed after the Pleistocene inception of the Greenland Ice Sheet. To date the structure, we conducted 40Ar/39Ar analyses on glaciofluvial sand and U-Pb analyses on zircon separated from glaciofluvial pebbles of impact melt rock, all sampled immediately downstream of Hiawatha Glacier. Unshocked zircon in the impact melt rocks dates to ~1915 million years (Ma), consistent with felsic intrusions found in local bedrock. The 40Ar/39Ar data indicate Late Paleocene resetting and shocked zircon dates to 57.99 ± 0.54 Ma, which we interpret as the impact age. Consequently, the Hiawatha impact structure far predates Pleistocene glaciation and is unrelated to either the Paleocene-Eocene Thermal Maximum or flood basalt volcanism in east Greenland. However, it was contemporaneous with the Paleocene Carbon Isotope Maximum, although the impact’s exact paleoenvironmental and climatic significance awaits further investigation.
Intestinal Bacterial Translocation Contributes to Diabetic Kidney Disease

Significance Statement Intestinal barrier dysfunction—a “leaky gut”—reportedly contributes to pathological processes in some diseases. In a mouse model, the authors induced diabetic kidney disease, leading to impaired intestinal integrity and inflammation, with IL-17 upregulation. This allowed intestine-derived Klebsiella oxytoca and elevated IL-17 to translocate to the circulation and kidneys, then accelerate kidney injury, especially in diabetic knockout mice lacking mitochondrial antiviral signaling protein (MAVS). Stimulation of tubular epithelial cells with K. oxytoca activated the MAVS pathway and phosphorylation of Stat3 and ERK1/2, leading to production of kidney injury molecule-1 (KIM-1). Systemic MAVS is renoprotective in diabetic mice by an intestinal protective role and the dominant inhibitory effects on suppressing KIM-1 expression under K. oxytoca supernatant or IL-17 stimulation. Controlling intestinal homeostasis may offer a therapeutic strategy in diabetic kidney disease. Visual Abstract Background In recent years, many studies have focused on the intestinal environment to elucidate pathogenesis of various diseases, including kidney diseases. Impairment of the intestinal barrier function, the “leaky gut,” reportedly contributes to pathologic processes in some disorders. Mitochondrial antiviral signaling protein (MAVS), a component of innate immunity, maintains intestinal integrity. The effects of disrupted intestinal homeostasis associated with MAVS signaling in diabetic kidney disease remains unclear. Methods To evaluate the contribution of intestinal barrier impairment to kidney injury under diabetic conditions, we induced diabetic kidney disease in wild-type and MAVS knockout mice through unilateral nephrectomy and streptozotocin treatment. We then assessed effects on the kidney, intestinal injuries, and bacterial translocation. Results MAVS knockout diabetic mice showed more severe glomerular and tubular injuries compared with wild-type diabetic mice. Owing to impaired intestinal integrity, the presence of intestine-derived Klebsiella oxytoca and elevated IL-17 were detected in the circulation and kidneys of diabetic mice, especially in diabetic MAVS knockout mice. Stimulation of tubular epithelial cells with K. oxytoca activated MAVS pathways and the phosphorylation of Stat3 and ERK1/2, leading to the production of kidney injury molecule-1 (KIM-1). Nevertheless, MAVS inhibition induced inflammation in the intestinal epithelial cells and KIM-1 production in tubular epithelial cells under K. oxytoca supernatant or IL-17 stimulation. Treatment with neutralizing anti–IL-17 antibody treatment had renoprotective effects. In contrast, LPS administration accelerated kidney injury in the murine diabetic kidney disease model. Conclusions Impaired MAVS signaling both in the kidney and intestine contributes to the disrupted homeostasis, leading to diabetic kidney disease progression. Controlling intestinal homeostasis may offer a novel therapeutic approach for this condition.
A systematic review and meta-analysis of studies of reactivity to digital in-the-moment measurement of health behaviour

ABSTRACT Self-report measures of health behaviour have several limitations including measurement reactivity, i.e., changes in people’s behaviour, cognitions or emotions due to taking part in research. This systematic review investigates whether digital in-the-moment measures induce reactivity to a similar extent and why it occurs. Four databases were searched in December 2020. All observational or experimental studies investigating reactivity to digital in-the-moment measurement of a range of health behaviours were included if they were published in English in 2008 or later. Of the 11,723 records initially screened, 30 publications reporting on 31 studies were included in the qualitative synthesis/ 7 studies in the quantitative synthesis. Eighty-one percent of studies focused on reactivity to the measurement of physical activity indicators; small but meaningful pooled effects were found (Cohen’s ds: 0.27–0.30). Only a small number of studies included other behaviours, yielding mixed results. Digital in-the-moment measurement of behaviour thus may be as prone to reactivity as self-reports in questionnaires. Measurement reactivity may be amplified by (1) ease of changing the behaviour (2) awareness of being measured and social desirability, and (3) resolving discrepancies between actual and desired behaviour through self-regulation.
Black mothers’ birthing experiences: in search of birthing justice

ABSTRACT Objectives Previous studies have suggested that often, Black mothers’ birthing experiences are not what they expected because of how they were treated by healthcare providers during labor and birth. Our goal in this study was to ask Black mothers who had recently given birth about the quality of their birthing experiences as well as their level of respect from, trust in, and satisfaction with their maternity healthcare providers. Design This study gathered data from Black mothers (N = 209) who had given birth within the past two years, using a cross-sectional online survey measuring several variables about the birthing experience including types of healthcare provider communication, provider respect for the mother, trust, birth satisfaction, and emotional responses to birth. Results Provider-centered communication, although preferred by some mothers, was associated with lower birth satisfaction and stronger negative emotions whereas positive birth satisfaction was linked to patient-centered communication which resulted in positive emotions. While most mothers reported overall satisfaction with their birth experience, nearly half reported experiencing some degree of disrespect from their healthcare providers during labor and birth. Moreover, trust and respect mediated the relationship for patient-centered communication with positive emotion and birth satisfaction. Over one-third of participants gave birth with a certified nurse midwife attending. There were no differences in perception of being respected or the quality of birth given the professional identity of the provider as an Obstetrician/Gynecologist or as a midwife. The advice suggested by Black mothers for their healthcare providers was instructive in identifying ways those providers could better serve their patients during birth. Conclusion This study showed that there is still additional work that needs to be done for racial equity and respect during birth. Practical implications for addressing health inequities are discussed.
Comparative Study of Bayesian Information Borrowing Methods in Oncology Clinical Trials

PURPOSE With deeper insight into precision medicine, more innovative oncology trial designs have been proposed to contribute to the characteristics of novel antitumor drugs. Bayesian information borrowing is an indispensable part of these designs, which shows great advantages in improving the efficiency of clinical trials. Bayesian methods provide an effective framework when incorporating information. However, the key point lies in how to choose an appropriate method for complex oncology clinical trials. METHODS We divided the borrowing information scenarios into concurrent and nonconcurrent scenarios according to whether the data to be borrowed are observed at the same time as in the current trial or not. Then, we provided an overview of the methods in each scenario. Performance comparison of different methods is carried out with regard to the type I error and power. RESULTS As demonstrated by the simulation results in each borrowing scenario, the Bayesian hierarchical model and its extensions are more appropriate for concurrent borrowing. The simulation results demonstrate that the Bayesian hierarchical model shows great advantages when the arms are homogeneous. However, such a method should be adopted with caution when heterogeneity exists. We recommend the other methods, considering heterogeneity. Borrow information from informative priors is more suggested for nonconcurrent borrowing scenarios. Multisource exchangeability models are more suitable for multiple historical trials, while meta-analytic-predictive prior should be carefully applied. CONCLUSION Bayesian information borrowing is useful and can improve the efficiency of clinical trial designs. However, we should carefully choose an appropriate information borrowing method when facing a practical innovative oncology trial, as an appropriate method is essential to provide ideal design performance. Bayesian information borrowing is an indispensable part of innovative oncology trial designs which provides an effective framework when incorporating external information. The key point lies in how to choose an appropriate borrowing method. This paper divided the borrowing information scenarios into concurrent and non-concurrent scenarios according to whether the data to be borrowed are observed at the same time as in the current trial or not. Recommendations for the application scenarios are made based on extensive simulations.
The Pathological and Clinical Diversity of Acute Vascular Rejection in Kidney Transplantation

Background. Vascular rejection (VR) is characterized by arteritis, steroid resistance, and increased graft loss but is poorly described using modern diagnostics. Methods. We screened 3715 consecutive biopsies and retrospectively evaluated clinical and histological phenotypes of VR (n = 100) against rejection without arteritis (v0REJ, n = 540) and normal controls (n = 1108). Results. Biopsy sample size affected the likelihood of arterial sampling, VR diagnosis, and final Banff v scores (P < 0.001). Local v and cv scores were greatest in larger arteries (n = 258). VR comprised 15.6% of all rejection episodes, presented earlier (median 1.0 mo, interquartile range, 0.4–8 mo) with higher serum creatinine levels and inferior graft survival, versus v0REJ (P < 0.001). Early VR (≤1 mo) was common (54%) and predicted by sensitization, delayed function, and prior corticosteroid use, with associated acute dysfunction and optimal therapeutic response, independent of Banff v score. Late VR followed under-immunosuppression in 71.4% (noncompliance 38.8%, iatrogenic 32.6%), and was associated with chronic interstitial fibrosis, incomplete renal functional recovery and persistent inflammation using sequential histopathology. The etiology was “pure” antibody-mediated VR (n = 21), mixed VR (n = 36), and “pure” T cell–mediated VR (n = 43). Isolated VR (n = 34, Banff i < 1 without tubulitis) comprised 24 T cell–mediated VR and 10 antibody-mediated VR, presenting with mild renal dysfunction, minimal Banff acute scores, and better graft survival compared with inflamed VR. Interstitial inflammation influenced acute renal dysfunction and early treatment response, whereas chronic tubulointerstitial damage determined long-term graft loss. Conclusions. VR is a heterogenous entity influenced by time-of-onset, pathophysiology, accompanying interstitial inflammation and fibrosis. Adequate histological sampling is essential for its accurate diagnostic classification and treatment.
BLOOD FLOW RESTRICTED WALKING IN ELDERLY INDIVIDUALS WITH KNEE OSTEOARTHRITIS: A FEASIBILITY STUDY

Objective To investigate whether blood flow restricted walking exercise is feasible in patients with knee osteoarthritis, and to examine changes in functional performance and self-reported function. Design Feasibility study. Patients and methods Fourteen elderly individuals diagnosed with knee osteoarthritis participated in 8–10 weeks of outdoor walking (4 km/h, 20 min/session, 4 times/week) with partial blood flow restriction applied to the affected leg. Adherence, drop-outs and adverse events were registered. Timed Up and Go test, 30-s sit-to-stand performance, 40-m fast-paced walk speed, stair-climbing and Knee Osteoarthritis Outcome Score were assessed pre- and post-training. Results Nine participants completed the intervention, while 5 participants withdrew (4 due to intervention-related reasons). In non-completing participants baseline body mass index (BMI) (p = 0.05) and knee pain (p = 0.06) were higher, while gait performance (p = 0.04) was lower. Considering completed case data, the training-adherence rate was 93%, while mean knee pain in the affected leg was 0.7 on a numerical rating scale of 0–10. Functional performance improved, while self-reported function remained unchanged. Conclusion Blood flow restricted walking exercise appeared feasible in patients with knee osteoarthritis. Participants who completed the intervention protocol demonstrated improvements in functional performance, with no changes in self-reported function. LAY ABSTRACT Patients with knee osteoarthritis typically experience knee joint pain and functional disability. Consequently, it is beneficial for these patients to engage in tolerable exercise programmes to enhance their functional performance. This study examined the feasibility of 8–10 weeks of blood flow restricted (BFR) walking exercise in patients with long-term knee osteoarthritis. The exercise programme was feasible, did not exacerbate knee pain or provoke cuff discomfort, and produced improved functional performance in those participants (9/14) who completed the intervention protocol (93% adherence rate). Notably however, 4 patients withdrew from the study due to intervention-related reasons. In this study, feasibility and adherence to BFR-walking appeared to depend on individual factors, with high body mass index, high perceived knee pain, and low baseline levels of fast-paced walking, predisposing to low adherence to training. Thus, these individual characteristics must be taken into account when administering BFR-walking exercise in patients with knee osteoarthritis.
Dissecting The role of Plasmodium metacaspase-2 in malaria gametogenesis and sporogony

ABSTRACT The family of apicomplexan specific proteins contains caspases–like proteins called “metacaspases”. These enzymes are present in the malaria parasite but absent in human; therefore, these can be explored as potential drug targets. We deleted the MCA-2 gene from Plasmodium berghei genome using a gene knockout strategy to decipher its precise function. This study has identified that MCA-2 plays an important role in parasite transmission since it is critical for the formation of gametocytes and for maintaining an appropriate number of infectious sporozoites required for sporogony. It is noticeable that a significant reduction in gametocyte, oocysts, ookinete and sporozoites load along with a delay in hepatocytes invasion were observed in the MCA-2 knockout parasite. Furthermore, a study found the two MCA-2 inhibitory molecules known as C-532 and C-533, which remarkably inhibited the MCA-2 activity, abolished the in vitro parasite growth, and also impaired the transmission cycle of P. falciparum and P. berghei in An. stephensi. Our findings indicate that the deletion of MCA-2 hampers the Plasmodium development during erythrocytic and exo-erythrocytic stages, and its inhibition by C-532 and C-533 critically affects the malaria transmission biology.
Balancing conduction velocity error in cardiac electrophysiology using a modified quadrature approach

Conduction velocity error is often the main culprit behind the need for very fine spatial discretizations and high computational effort in cardiac electrophysiology problems. In light of this, a novel approach for simulating an accurate conduction velocity in coarse meshes with linear elements is suggested based on a modified quadrature approach. In this approach, the quadrature points are placed at arbitrary offsets of the isoparametric coordinates. A numerical study illustrates the dependence of the conduction velocity on the spatial discretization and the conductivity when using different quadrature rules and calculation approaches. Additionally, examples using the modified quadrature in coarse meshes for wave propagation demonstrate the improved accuracy of the conduction velocity with this method. This novel approach possesses great potential in reducing the computational effort required but remains limited to specific linear elements and experiences a reduction in accuracy for irregular meshes and heterogeneous conductivities. Further research can focus on developing an adaptive quadrature and extending the approach to other element formulations in order to make the approach more generally applicable.
Understanding client engagement in digital mental health interventions: An investigation of the eTherapy Attitudes and Process Questionnaire

Abstract Aims Digital mental health services may increase the accessibility and affordability of mental health treatments. However, client dropout a low use is often reported. The purpose of the current study was to investigate the structural validity of the e‐Therapy Attitudes and Process (eTAP) questionnaire, as a theoretically based (theory of planned behavior) tool for understanding ongoing client engagement intentions with digital mental health treatments. The possible role of eHealth literacy in predicting behavioral intentions to use digital mental health treatments was also examined. Methods Participants were 244 Australian‐based adults aged between 18 and 56 years, who were currently using a digital mental health tool. Data were collected via online survey. Results Confirmatory Factor Analysis was conducted, with good model fit obtained following two theoretically supported modifications. Moderated hierarchical regression supported the utility of the theory of planned behavior in predicting behavioral intentions, with attitudes emerging as a strong and consistent individual predictor. No support was found for the moderating role or individual significance of eHealth literacy. Conclusions These findings support the clinical and research use of the eTAP as a theory‐based measure to understand client engagement in digital mental health interventions. The study also highlights the need for interventions to target attitudes to improve clients' ongoing engagement in digital mental health.
Vaccine‐preventable disease hospitalized patients with heart failure with reduced ejection fraction

Over five million Americans suffer from heart failure (HF), and this is associated with multiple chronic comorbidities and recurrent decompensation. Currently, there is an increased incidence in vaccine‐preventable diseases (VPDs). We aim to investigate the impact of HF with reduced ejection fraction (HFrEF) in patients hospitalized with VPDs.
Prolonged Cardiac Monitoring and Stroke Recurrence

Background and Objectives Prolonged poststroke cardiac rhythm monitoring (PCM) reveals a substantial proportion of patients with ischemic stroke (IS) with atrial fibrillation (AF) not detected by conventional rhythm monitoring strategies. We evaluated the association between PCM and the institution of stroke preventive strategies and stroke recurrence. Methods We searched MEDLINE and SCOPUS databases to identify studies reporting stroke recurrence rates in patients with history of recent IS or TIA receiving PCM compared with patients receiving conventional cardiac rhythm monitoring. Pairwise meta-analyses were performed under the random effects model. To explore for differences between the monitoring strategies, we combined direct and indirect evidence for any given pair of monitoring devices assessed within a randomized controlled trial (RCT). Results We included 8 studies (5 RCTs, 3 observational; 2,994 patients). Patients receiving PCM after their index event had a higher rate of AF detection and anticoagulant initiation in RCTs (risk ratio [RR] 3.91, 95% CI 2.54–6.03; RR 2.16, 95% CI 1.66–2.80, respectively) and observational studies (RR 2.06, 95% CI 1.57–2.70; RR 2.01, 95% CI 1.43–2.83, respectively). PCM was associated with a lower risk of recurrent stroke during follow-up in observational studies (RR 0.29, 95% CI 0.15–0.59), but not in RCTs (RR 0.72, 95% CI 0.49–1.07). In indirect analyses of RCTs, the likelihood of AF detection and anticoagulation initiation was higher for implantable loop recorders compared with Holter monitors and external loop recorders. Discussion PCM after an IS or TIA can lead to higher rates of AF detection and anticoagulant initiation. There is no solid RCT evidence supporting that PCM may be associated with lower stroke recurrence risk.
High-flow nasal cannula for respiratory failure in adult patients

The high-flow nasal cannula (HFNC) has been recently used in several clinical settings for oxygenation in adults. In particular, the advantages of HFNC compared with low-flow oxygen systems or non-invasive ventilation include enhanced comfort, increased humidification of secretions to facilitate expectoration, washout of nasopharyngeal dead space to improve the efficiency of ventilation, provision of a small positive end-inspiratory pressure effect, and fixed and rapid delivery of an accurate fraction of inspired oxygen (FiO2) by minimizing the entrainment of room air. HFNC has been successfully used in critically ill patients with several conditions, such as hypoxemic respiratory failure, hypercapneic respiratory failure (exacerbation of chronic obstructive lung disease), post-extubation respiratory failure, pre-intubation oxygenation, and others. However, the indications are not absolute, and much of the proven benefit remains subjective and physiologic. This review discusses the practical application and clinical uses of HFNC in adults, including its unique respiratory physiologic effects, device settings, and clinical indications.