Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel method for estimating connectivity‐based parcellation of the human brain from diffusion MRI: Application to an aging cohort

Connectivity‐based parcellation (CBP) methods are used to define homogenous and biologically meaningful parcels or nodes—the foundations of brain network fingerprinting—by grouping voxels with similar patterns of brain connectivity. However, we still lack a gold standard method and the use of CBPs to study the aging brain remains scarce. Our study proposes a novel CBP method from diffusion MRI data and shows its potential to produce a more accurate characterization of the longitudinal alterations in brain network topology occurring in aging. For this, we constructed whole‐brain connectivity maps from diffusion MRI data of two datasets: an aging cohort evaluated at two timepoints (mean interval time: 52.8 ± 7.24 months) and a normative adult cohort—MGH‐HCP. State‐of‐the‐art clustering techniques were used to identify the best performing technique. Furthermore, we developed a new metric (connectivity homogeneity fingerprint [CHF]) to evaluate the success of the final CBP in improving regional/global structural connectivity homogeneity. Our results show that our method successfully generates highly homogeneous parcels, as described by the significantly larger CHF score of the resulting parcellation, when compared to the original. Additionally, we demonstrated that the developed parcellation provides a robust anatomical framework to assess longitudinal changes in the aging brain. Our results reveal that aging is characterized by a reorganization of the brain's structural network involving the decrease of intra‐hemispheric, increase of inter‐hemispheric connectivity, and topological rearrangement. Overall, this study proposes a new methodology to perform accurate and robust evaluations of CBP of the human brain.
Systematic review and meta‐analysis evaluating the effects electric bikes have on physiological parameters

There is a universal need to increase the number of adults meeting physical activity (PA) recommendations to help improve health. In recent years, electrically assisted bicycles (e‐bikes) have emerged as a promising method for supporting people to initiate and maintain physical activity levels. To the best of our knowledge, there have been no meta‐analyses conducted to quantify the difference in physiological responses between e‐cycling with electrical assistance, e‐cycling without assistance, conventional cycling, and walking.
Cluster Analysis of Primary Care Physician Phenotypes for Electronic Health Record Use: Retrospective Cohort Study

Background Electronic health records (EHRs) have become ubiquitous in US office-based physician practices. However, the different ways in which users engage with EHRs remain poorly characterized. Objective The aim of this study is to explore EHR use phenotypes among ambulatory care physicians. Methods In this retrospective cohort analysis, we applied affinity propagation, an unsupervised clustering machine learning technique, to identify EHR user types among primary care physicians. Results We identified 4 distinct phenotype clusters generalized across internal medicine, family medicine, and pediatrics specialties. Total EHR use varied for physicians in 2 clusters with above-average ratios of work outside of scheduled hours. This finding suggested that one cluster of physicians may have worked outside of scheduled hours out of necessity, whereas the other preferred ad hoc work hours. The two remaining clusters represented physicians with below-average EHR time and physicians who spend the largest proportion of their EHR time on documentation. Conclusions These findings demonstrate the utility of cluster analysis for exploring EHR use phenotypes and may offer opportunities for interventions to improve interface design to better support users’ needs.
Daidzein Mitigates Oxidative Stress and Inflammation in the Injured Kidney of Ovariectomized Rats: AT1 and Mas Receptor Functions.

INTRODUCTION Chronic kidney disease (CKD) is a health problem in postmenopausal women, and renal fibrosis is a common feature of CKD. In the renin-angiotensin system, oxidative stress and inflammation are involved in the pathogenesis of renal fibrosis. This study investigated the effect of the phytoestrogen daidzein on oxidative stress and inflammation and the mediation of the angiotensin AT1 and Mas receptors in a fibrotic model of kidney disease of ovariectomized (OVX) rats. METHODS Unilateral ureteral obstruction (UUO) was performed to induce chronic renal inflammation and fibrosis in 84 OVX rats, which were divided into four main groups (each = 21) including sham + Vehicle (Veh.), UUO + Veh, UUO + estradiol (E2), and UUO + daidzein. Each main group composed of three subgroups (n = 7), which received saline, losartan (AT1R antagonist), or A779 (Mas receptor [MasR] antagonist) for 15 days after UUO or sham operation. Renal pathology, serum and kidney oxidants and antioxidants, malondialdehyde (MDA), nitric oxide metabolites (NOx), protein carbonyl (PC), and pro-inflammatory and antiinflammatory cytokines were examined. RESULTS UUO increased renal glomerulosclerosis, inflammation, serum and kidney tissue MDA, NOx, and PC together with an increase in TNF-α, IL-1β, and IL-6 expression. Moreover, UUO decreased superoxide dismutase and glutathione peroxidase and catalase activity, total antioxidant capacity, and IL-10 level in the serum and kidney tissue. AT1R blockade reduced and MasR blockade worsened renal impairment. Daidzein and E2 alone and in co-treatment with losartan significantly ameliorated these effects. CONCLUSION Via interaction with AT1R and MasRs, daidzein improved glomerulosclerosis, oxidative stress, and inflammation in UUO-OVX rats. Daidzein may be a candidate for estrogen replacement therapy in postmenopausal or older women against postmenopausal kidney damage. DOI: 10.52547/ijkd.6602.
Design of Autonomous Cruise Controller with Linear Time Varying Model

Cruise control is a technology for automatically maintaining a steady speed of vehicle as set by the driver via controlling throttle valve and brake of vehicle. In this paper we investigate cruise controller design method with consideration for distance to vehicle ahead. We employ linear time varying (LTV) model to describe longitudinal vehicle dynamic motion. With this LTV system we approximately model the nonlinear dynamics of vehicle speed by frequent update of the system parameters. In addition we reformulate the LTV system by transforming distance to leading vehicle into variation of system parameters of the model. Note that in conventional control problem formulation this distance is considered as disturbance which should be rejected. Consequently a controller can be designed by pole placement at each instance of parameter update, based on the linear model with the present system parameters. The validity of this design method is examined by simulation study.
The zebrafish cohesin protein Sgo1 is required for cardiac function and eye development

Cohesinopathies is a term that refers to/covers rare genetic diseases caused by mutations in the cohesin complex proteins. The cohesin complex is a multiprotein complex that facilitates different aspects of cell division, gene transcription, DNA damage repair, and chromosome architecture. Shugoshin proteins prevent the cohesin complex from premature dissociation from chromatids during cell division. Patients with a homozygous missense mutation in SGO1, which encodes for Shugoshin1, have problems with normal pacing of the heart and gut.
Modulation of LTCC Pathways by a Melusin Mimetic Increases Ventricular Contractility During LPS-Induced Cardiomyopathy

ABSTRACT Aim: Sepsis-induced cardiomyopathy is commonplace and carries an increased risk of death. Melusin, a cardiac muscle-specific chaperone, exerts cardioprotective function under varied stressful conditions through activation of the AKT pathway. The objective of this study was to determine the role of melusin in the pathogenesis of lipopolysaccharide (LPS)-induced cardiac dysfunction and to explore its signaling pathway for the identification of putative therapeutic targets. Methods and results: Prospective, randomized, controlled experimental study in a research laboratory. Melusin overexpressing (MelOV) and wild-type (MelWT) mice were used. MelOV and MelWT mice were injected intraperitoneally with LPS. Cardiac function was assessed using trans-thoracic echocardiography. Myocardial expression of L-type calcium channel (LTCC), phospho-Akt and phospho-Gsk3-b were also measured. In separate experiments, wild-type mice were treated post-LPS challenge with the allosteric Akt inhibitor Arq092 and a mimetic peptide (R7W-MP) targeting the LTCC. The impact of these therapies on protein–protein interactions, cardiac function, and survival was assessed. MelOV mice had limited derangement in cardiac function after LPS challenge. Protection was associated with higher Akt and Gsk3-b phosphorylation and restored LTCC density. Pharmacological inhibition of Akt activity reversed melusin-dependent cardiac protection. Treatment with R7W-MP preserved cardiac function in wild-type mice after LPS challenge and significantly improved survival. Conclusions: This study identifies AKT/Melusin as a key pathway for preserving cardiac function following LPS challenge. The cell-permeable mimetic peptide (R7W-MP) represents a putative therapeutic for sepsis-induced cardiomyopathy.
DLC-1 facilitates germ granule assembly in Caenorhabditis elegans embryo

Germ granules are cytoplasmic assemblies of RNA-binding proteins (RBPs) required for germ cell development and fertility. During the first four cell divisions of the Caenorhabditis elegans zygote, regulated assembly of germ (P) granules leads to their selective segregation to the future germ cell. Here we investigate the role of DLC-1, a hub protein implicated in stabilization and function of diverse protein complexes, in maintaining P granule integrity. We find that DLC-1 directly interacts with several core P granule proteins, predominantly during embryogenesis. The loss of dlc-1 disrupts assembly of P granule components into phase-separated organelles in the embryos, regardless of whether or not DLC-1 directly interacts with these proteins. Finally, we infer that P granule dispersal in the absence of dlc-1 is likely independent of DLC-1’s function as a subunit of the dynein motor and does not result from a loss of cell polarity.
Serum Concentration of CD137 and Tumor Infiltration by M1 Macrophages Predict the Response to Sintilimab plus Bevacizumab Biosimilar in Advanced Hepatocellular Carcinoma Patients

Abstract Purpose: This study aimed to investigate the biomarkers of sintilimab (anti–PD-1) plus IBI305 (a bevacizumab biosimilar) in advanced hepatocellular carcinoma (HCC), as well as their safety and efficacy. Patients and Methods: A total of 50 patients with advanced HCC received sintilimab (200 mg) plus IBI305 (7.5 or 15 mg/kg), treated every 3 weeks in a phase Ib clinical study. We performed baseline serum cytokine analysis using bead-based multiplex immunoassay and multiplex immunofluorescence on tissue specimens to discover novel biomarkers of response to VEGF/PD-1 combination therapy in HCC. Results: The overall response rate was 34.0% (17/50). The median progression-free survival (PFS) and the median overall survival were 10.5 and 20.2 months, respectively. The incidence of grade 3 to 5 adverse events was lower in the 7.5 mg/kg (13.8%) than in the 15 mg/kg (28.6%) dose groups. Biomarker analysis showed that the serum CD137 concentration was significantly higher in patients with clinical benefit (CB) than in those without CB (median, 32.8 pg/mL vs. 19.8 pg/mL, P = 0.034). A markedly longer PFS was observed in patients with high CD137 concentrations compared with those with low concentrations (median, 14.2 months vs. 4.1 months, P = 0.001). The higher density of M1 macrophages (CD68+CD163–) in the stroma was also associated with higher efficacy (P = 0.033) and a longer PFS (P = 0.024). Conclusions: Sintilimab plus IBI305 was well tolerated and was effective therapy for advanced HCC. Both serum concentrations of CD137 and tumor infiltration of M1 macrophages may serve as potential predictive biomarkers. See related commentary by Cappuyns and Llovet, p. 3405
Deficient mitochondrial respiration in astrocytes impairs trace fear conditioning and increases naloxone‐precipitated aversion in morphine‐dependent mice

Mitochondria are abundant in the fine processes of astrocytes, however, potential roles for astrocyte mitochondria remain poorly understood. In the present study, we performed a systematic examination of the effects of abnormal oxidative phosphorylation in astrocytes on several mouse behaviors. Impaired astrocyte oxidative phosphorylation was produced by astrocyte‐specific deletion of the nuclear mitochondrial gene, Cox10, that encodes an accessory protein of complex IV, the protoheme:heme‐O‐farnesyl transferase. As expected, conditional deletion of the Cox10 gene in mice (cKO mice) significantly reduced expression of COX10 and Cytochrome c oxidase subunit I (MTCO1) of Complex IV, resulting in decreased oxidative phosphorylation without significantly affecting glycolysis. No effects of the deletion were observed on locomotor activity, anxiety‐like behavior, nociception, or spontaneous alternation. Cox10 cKO female mice exhibited mildly impaired novel object recognition, while Cox10 cKO male mice were moderately deficient in trace fear conditioning. No group‐related changes were observed in conditional place preference (CPP) that assessed effects of morphine on reward. In contrast to CPP, Cox10 cKO mice demonstrated significantly increased aversive behaviors produced by naloxone‐precipitated withdrawal following chronic exposure to morphine, that is, jumping and avoidance behavior as assessed by conditional place aversion (CPA). Our study suggests that astrocyte oxidative phosphorylation may contribute to behaviors associated with greater cognitive load and/or aversive and stressful conditions.
Impact of COVID-19 Pandemic on Mental Health and Quality of Life. An Exploratory Study During the First Outbreak in Italy

The coronavirus pandemic has been sweeping the world for more than a year. As physical health begins to stabilize in the western world, an increasing concern is related to the impact of the virus and its containment measures on people’s mental health. This work aimed to explore the effect of demographic factors (age, gender, level of education, and socioeconomic status) and variables such as fear of COVID-19 and social support in predicting the quality of life and mental health of adults during the first wave of the pandemic in Italy. Through an online survey with 1087 Italian adults (M = 39.7, SD = 16.39; 74.4% women), gender and socioeconomic status emerged as crucial factors in determining differences regarding people’s responses and reactions to the pandemic. In addition, the results highlighted the importance of perceived social support and a moderate fear of COVID-19 in predicting people’s quality of life and mental health. The study suggests important guidelines for the development of interventions to support the population’s well-being and mental health.
The Public Perception of the #GeneEditedBabies Event Across Multiple Social Media Platforms: Observational Study

Background In November 2018, a Chinese researcher reported that his team had applied clustered regularly interspaced palindromic repeats or associated protein 9 to delete the gene C-C chemokine receptor type 5 from embryos and claimed that the 2 newborns would have lifetime immunity from HIV infection, an event referred to as #GeneEditedBabies on social media platforms. Although this event stirred a worldwide debate on ethical and legal issues regarding clinical trials with embryonic gene sequences, the focus has mainly been on academics and professionals. However, how the public, especially stratified by geographic region and culture, reacted to these issues is not yet well-understood. Objective The aim of this study is to examine web-based posts about the #GeneEditedBabies event and characterize and compare the public’s stance across social media platforms with different user bases. Methods We used a set of relevant keywords to search for web-based posts in 4 worldwide or regional mainstream social media platforms: Sina Weibo (China), Twitter, Reddit, and YouTube. We applied structural topic modeling to analyze the main discussed topics and their temporal trends. On the basis of the topics we found, we designed an annotation codebook to label 2000 randomly sampled posts from each platform on whether a supporting, opposing, or neutral stance toward this event was expressed and what the major considerations of those posts were if a stance was described. The annotated data were used to compare stances and the language used across the 4 web-based platforms. Results We collected >220,000 posts published by approximately 130,000 users regarding the #GeneEditedBabies event. Our results indicated that users discussed a wide range of topics, some of which had clear temporal trends. Our results further showed that although almost all experts opposed this event, many web-based posts supported this event. In particular, Twitter exhibited the largest number of posts in opposition (701/816, 85.9%), followed by Sina Weibo (968/1140, 84.91%), Reddit (550/898, 61.2%), and YouTube (567/1078, 52.6%). The primary opposing reason was rooted in ethical concerns, whereas the primary supporting reason was based on the expectation that such technology could prevent the occurrence of diseases in the future. Posts from these 4 platforms had different language uses and patterns when they expressed stances on the #GeneEditedBabies event. Conclusions This research provides evidence that posts on web-based platforms can offer insights into the public’s stance on gene editing techniques. However, these stances vary across web-based platforms and often differ from those raised by academics and policy makers.
An Evolutionarily Conserved AU-Rich Element in the 3' Untranslated Region of a Transcript Misannotated as a Long Noncoding RNA Regulates RNA Stability

One of the primary mechanisms of post-transcriptional gene regulation is the modulation of RNA stability. We recently discovered that LINC00675, a transcript annotated as a long noncoding RNA (lncRNA), is transcriptionally regulated by FOXA1 and encodes a highly conserved small protein that localizes to the endoplasmic reticulum, hence renamed as FORCP (FOXA1-regulated conserved small protein). ABSTRACT One of the primary mechanisms of post-transcriptional gene regulation is the modulation of RNA stability. We recently discovered that LINC00675, a transcript annotated as a long noncoding RNA (lncRNA), is transcriptionally regulated by FOXA1 and encodes a highly conserved small protein that localizes to the endoplasmic reticulum, hence renamed as FORCP (FOXA1-regulated conserved small protein). Here, we show that the endogenous FORCP transcript is rapidly degraded and rendered unstable as a result of 3’UTR-mediated degradation. Surprisingly, although the FORCP transcript is a canonical nonsense-mediated decay (NMD) and microRNA (miRNA) target, we found that it is not degraded by NMD or miRNAs. Targeted deletion of an evolutionarily conserved region in the FORCP 3’UTR using CRISPR/Cas9 significantly increased the stability of the FORCP transcript. Interestingly, this region requires the presence of an immediate downstream 55-nt-long sequence for transcript stability regulation. Functionally, colorectal cancer cells lacking this conserved region expressed from the endogenous FORCP locus displayed decreased proliferation and clonogenicity. These data demonstrate that the FORCP transcript is destabilized via conserved elements within its 3’UTR and emphasize the need to interrogate the function of a given 3’UTR in its native context.
Validation of a smart shirt for heart rate variability measurements at rest and during exercise

Heart rate variability (HRV) monitoring is a promising option to estimate the autonomic nervous system regulation responding to exercise. Textiles with embedded sensors recording heartbeat intervals are a simple tool for data collection. The so‐called smart shirts offer comfort for daily use and are managed easily. Their measurement accuracy for HRV calculation at rest is promising, but remains questionable during exercise. Therefore, the present study validated the Ambiotex smart shirt using HRV indices (root mean square of successive differences, rel. HF power [high‐frequency power percentage of total power] and rel. LF [low‐frequency power percentage of total power] power) during exercise. Eighty‐three healthy participants (31 ± 6 years; 39 females, 44 males) completed an incremental exercise test on a bicycle ergometer wearing the smart shirt and an electrocardiogram simultaneously. We compared HRV indices of segments at rest (5 min), at warm‐up (3 min) and twice at the exercise test (each 5 min). At rest and at warm‐up, we observed excellent linear relationship (r > 0.96; R2 > 0.94), excellent relative reliability (intraclass correlation coefficient ≥ 0.98; α ≥ 0.98) and acceptable agreement (bias < 10%). During the exercise test, measurement accuracy declined with increasing intensity but remained high (>0.8), although results for partial HRV indices were insufficient. In addition, percentage bias was unacceptable during an exercise test. However, the findings support the validity of the smart shirt for measuring HRV, especially at rest and at warm‐up. We suggest using the smart shirt for monitoring HRV indices on a daily basis, but caution should be taken in the interpretation of HRV indices obtained during moderate to vigorous exercise intensities.
The Performance Assessment of Self-Care Skills to Predict Adverse Events Post-Discharge

Background. The Performance Assessment of Self-Care Skills (PASS) is a standardized assessment of the ability to perform daily activities. Purposes. This preliminary exploratory study aimed to 1) explore the ability of four PASS tasks to predict adverse events (readmissions and injuries) in older adults following hospitalization; 2) compare PASS's predictive validity to that of a generic tool (SMAF) and OT clinical judgement. Method.Twenty-two older patients were assessed in hospital at discharge and at home one week later. Adverse events were documented for six months post-discharge. Sensitivity and specificity analyses (ROC curves, Fisher's exact tests) were performed. Findings. Two PASS tasks (telephone, medication), the SMAF-Social and OT clinical judgement could identify individuals at risk of readmission (AUC > 0.7; p < 0.05). Implications. Using the PASS to assess more cognitively demanding tasks could be a promising way to predict adverse events after discharge, as a complement to clinical judgment.