Miracle-dz/UniFAR-FTUs huggingface dataset:
CDC50A is required for aminophospholipid transport and cell fusion in mouse C2C12 myoblasts

ABSTRACT Myoblast fusion is essential for the formation of multinucleated muscle fibers and is promoted by transient changes in the plasma membrane lipid distribution. However, little is known about the lipid transporters regulating these dynamic changes. Here, we show that proliferating myoblasts exhibit an aminophospholipid flippase activity that is downregulated during differentiation. Deletion of the P4-ATPase flippase subunit CDC50A (also known as TMEM30A) results in loss of the aminophospholipid flippase activity and compromises actin remodeling, RAC1 GTPase membrane targeting and cell fusion. In contrast, deletion of the P4-ATPase ATP11A affects aminophospholipid uptake without having a strong impact on cell fusion. Our results demonstrate that myoblast fusion depends on CDC50A and may involve multiple CDC50A-dependent P4-ATPases that help to regulate actin remodeling. This article has an associated First Person interview with the first author of the paper.
Distributed learning episodes create a context fear memory outside the hippocampus that depends on perirhinal and anterior cingulate cortices

Damage to the hippocampus (HPC) typically causes retrograde amnesia for contextual fear conditioning. Repeating the conditioning over several sessions, however, can eliminate the retrograde amnesic effects. This form of reinstatement thus permits modifications to networks that can support context memory retrieval in the absence of the HPC. The present study aims to identify cortical regions that support the nonHPC context memory. Specifically, the contribution of the perirhinal cortex (PRH) and the anterior cingulate cortex (ACC) were examined because of their established importance to context memory. The findings show that context memories established through distributed reinstatement survive damage limited only to the HPC, PRH, or ACC. Combined lesions of the HPC and PRH, as well as the HPC and ACC, caused retrograde amnesia, suggesting that network modifications in the PRH and ACC enable context fear memories to become resistant to HPC damage.
Patterns of incident dementia codes during the COVID‐19 pandemic at an integrated healthcare system

The COVID‐19 pandemic delayed diagnosis and care for some acute conditions and reduced monitoring for some chronic conditions. It is unclear whether new diagnoses of chronic conditions such as dementia were also affected. We compared the pattern of incident Alzheimer's disease and related dementia (ADRD) diagnosis codes from 2017 to 2019 through 2020, the first pandemic year.
Modeled Impact of Seasonal Malaria Chemoprevention on District-Level Suspected and Confirmed Malaria Cases in Chad Based on Routine Clinical Data (2013–2018)

ABSTRACT. Sulfadoxine-pyrimethamine plus amodiaquine is delivered to children aged 3–59 months as seasonal malaria chemoprevention (SMC) in areas where transmission is highly seasonal such as Chad and other Sahelian countries. Although clinical trials show a 75% reduction in malaria cases, evidence of SMC’s impact at scale remains limited. Using data from the Chadian National Health Management Information System, we analyzed associations between SMC implementation during July–October and monthly district-level malaria incidence (suspected and confirmed outpatient cases) among children aged 0–59 months at health facilities in 23 health districts with SMC implementation during 2013–2018. Generalized additive models were fitted with separate cyclic cubic spline terms for each district to adjust for seasonality in cases. SMC implementation in Chad was associated, compared with no implementation, with lower monthly counts of both suspected (rate ratio [RR]: 0.82, 95% CI: 0.72–0.94. P = 0.006) and confirmed malaria cases (RR: 0.81, 95% CI: 0.71–0.93, P = 0.003), representing around 20% reduction in malaria incidence. Sensitivity analyses showed effect sizes of up to 28% after modifying model assumptions. Caution should be exercised in interpreting our findings, which may not be comparable with other studies, and may over- or underestimate impact of SMC; not all malaria cases present at health facilities, not all suspected cases are tested, and not all facilities report cases consistently. This study’s approach presents a solution for employing readily available routine data to evaluate the impact of health interventions at scale without extensive covariate data. Further efforts are needed to improve the quality of routine data in Chad and elsewhere.
Transitioning From In-Person to Remote Clinical Research on Depression and Traumatic Brain Injury During the COVID-19 Pandemic: Study Modifications and Preliminary Feasibility From a Randomized Controlled Pilot Study

Background Telehealth has provided many researchers, especially those conducting psychosocial research, with the tools necessary to transition from in-person to remote clinical trials during the COVID-19 pandemic. A growing body of research supports the effectiveness of telemental health for a variety of psychiatric conditions, but few studies have examined telemental health for individuals with comorbid medical diagnoses. Furthermore, little is known about the remote implementation of clinical trials examining telemental health interventions. Objective This paper outlines the procedural modifications used to facilitate conversion of an in-person randomized controlled trial of cognitive behavioral therapy (CBT) for depression in individuals with traumatic brain injury (TBI; CBT-TBI) to a telemental health study administered remotely. Methods Given the nature of remote implementation and specific challenges experienced by individuals with TBI, considerations related to treatment delivery, remote consent, data management, neuropsychological assessment, safety monitoring, and delivery of supportive material have been discussed. Feasibility, acceptability, and safety were evaluated by examining attendance and participant responses on self-report measures of treatment satisfaction and suicidal behavior. Results High rates of treatment attendance, assessment completion, study retention, and satisfaction with the intervention and modality were reported by participants who completed at least one telemental health CBT-TBI session. Conclusions Study modifications are necessary when conducting a study remotely, and special attention should be paid to comorbidities and population-specific challenges (eg, cognitive impairment). Preliminary data support the feasibility, acceptability, and safety of remotely conducting a randomized controlled trial of CBT-TBI. Trial Registration ClinicalTrials.gov NCT03307070; https://clinicaltrials.gov/ct2/show/NCT03307070
Carbapenem-resistant Klebsiella pneumoniae colonization and infection is associated with lower overall survival in a cohort of haematopoietic stem-cell transplantation patients: mechanism of resistance and virulence by whole-genome sequencing.

Carbapenem-resistant Klebsiella pneumoniae (CRK) infections are a growing concern in immunocompromised patients. The aim of the present study was to evaluate the impact of CRK colonization and infection in overall mortality for haematopoietic stem-cell transplant (HSCT) patients. We also aimed to investigate resistance and virulence profiles of CRK isolates and assess their epidemiological and genetic relatedness. Patients in the HSCT unit were screened for colonization with CRK with weekly rectal swab or stool cultures and placed under contact precautions. We defined CRK colonization as positive culture from a swab or stool sample grown in MacConkey agar with meropenem at 1 µg ml-1. Demographic and clinical data were retrieved from the patients' charts and electronic records. According to resistance mechanisms and pulsed field gel electrophoresis profile, isolates were selected based on whole-genome sequencing (WGS) using MiSeq Illumina. Outcomes were defined as overall mortality (death up to D+100), and infection-related death (within 14 days of infection). We report a retrospective cohort of 569 haematopoietic stem-cell transplant patients with 105 (18.4 %) CRK colonizations and 30 (5.3 %) infections. blaKPC was the most frequent carbapenemase in our cohort with three isolates co-harbouring blaKPC and blaNDM. We found no difference in virulence profiles from the CRK isolates. There were also no significant differences in virulence profiles among colonization and infection isolates regarding genes encoding for type 1 and 3 fimbriae, siderophores, lipopolysaccharide and colibactin. In clonality analysis by PFGE and WGS, isolates were polyclonal and ST340 was the most prevalent. Overall survival at D+100 was 75.4 % in in CRK-colonized (P=0.02) and 35.7 % in infected patients and significantly lower than non-colonized patients (85.8 %; P<0.001). We found a higher overall mortality associated with colonization and infection; KPC was the main resistance mechanism for carbapenems. The polyclonal distribution of isolates and findings of CRK infection in patients not previously colonized suggest the need to reinforce antibiotic stewardship.
Effects of single versus dual antiplatelet therapy on the adverse events after transcatheter aortic valve implantation: A meta‐analysis

Dual antiplatelet therapy (DAPT) was currently recommended for transcatheter aortic valve implantation (TAVI) postoperative management in clinical application. However, POPular‐TAVI trial showed DAPT increased the incidence of adverse events compared to single antiplatelet therapy (SAPT). Herein, we performed a meta‐analysis to investigate the effect of SAPT versus DAPT on the adverse events after TAVI. Eleven studies were available from PubMed, Embase, Cochrane Library, and Web of Science from inception to April 1, 2021. The pooled effect size was presented as relative risk (RR) with 95% confidence intervals (CIs). The sensitivity analysis was used to assess the stability of analysis results, and Begg's test was applied to evaluate the publication bias. The Cochran Q test and the I2 statistic were used to evaluate the heterogeneity, and the source of heterogeneity was explored by meta‐regression. A total of 4804 patients were obtained, with 2257 in SAPT group and 2547 in DAPT group. Compared to the DAPT, SAPT was associated with the decreased risk of all‐cause bleeding (RR: 0.51, 95% CI: 0.44–0.61), major bleeding (RR: 0.53, 95% CI: 0.32–0.86), and minor bleeding (RR: 0.58, 95% CI: 0.34–0.98). There were no significant differences in mortality and myocardial infarction events, stroke events, and acute kidney injury between the two groups. SAPT was superior to DAPT in decreasing all‐cause bleeding, major bleeding, and minor bleeding, suggesting that SAPT could be preferentially recommended for TAVI postoperative management in most patients without another indication for DAPT and oral anticoagulation.
Outcomes Following Participation in a Support-Based Summer Camp for Children Who Stutter.

Purpose Self-help and support activities are often recommended for people who stutter, and there is growing interest in understanding whether and how such experiences might be beneficial for children who stutter. The purpose of this study was to explore the potential impact of participation in Camp SAY, an overnight support-based summer camp experience for children who stutter, by measuring changes in scores on the Overall Assessment of the Speaker's Experience of Stuttering (OASES). Method Participants were 107 children who stutter (age range: 8-18 years) who attended Camp SAY during the summers of 2013, 2015, and/or 2016. We examined changes in OASES scores (a) pre- to postcamp, (b) the durability of changes 6 months after the conclusion of the camp, and group differences (c) between school-age campers and teenage campers and (d) between first-time campers and those who had previously attended the camp. Results Comparison of precamp to postcamp scores revealed significant improvements related to reactions to stuttering, quality of life, and overall adverse impact of stuttering. Scores on each subsection of the OASES were maintained (and further improved) 6 months after camp. There were no significant differences between school-age campers and teenage campers. Both first-time and returning campers showed significant improvements related to reactions to stuttering, though first-time campers had a significantly larger improvement in attitudes toward communication related to stuttering than returning campers. Conclusion These outcomes suggest that participation in support activities, like Camp SAY, is associated with significant reductions in the overall adverse impact of stuttering and can therefore be beneficial for children who stutter.
Genetic Counseling and Testing in African American Patients With Breast Cancer: A Nationwide Survey of US Breast Oncologists

PURPOSE To determine if physicians' self-reported knowledge, attitudes, and practices regarding genetic counseling and testing (GCT) vary by patients' race. METHODS We conducted a nationwide 49-item survey among breast oncology physicians in the United States. We queried respondents about their own demographics, clinical characteristics, knowledge, attitudes, practices, and perceived barriers in providing GCT to patients with breast cancer. RESULTS Our survey included responses from 277 physicians (females, 58.8%; medical oncologists, 75.1%; academic physicians, 61.7%; and Whites, 67.1%). Only 1.8% indicated that they were more likely to refer a White patient than refer an African American patient for GCT, and 66.9% believed that African American women with breast cancer have lower rates of GCT than White women. Regarding perceived barriers to GCT, 63.4% of respondents indicated that African American women face more barriers than White women do and 21% felt that African American women require more information and guidance during the GCT decision-making process than White women. Although 32% of respondents indicated that lack of trust was a barrier to GCT in all patients, 58.1% felt that this was a greater barrier for African American women (P < .0001). Only 13.9% believed that noncompliance with GCT is a barrier for all patients, whereas 30.6% believed that African American women are more likely than White women to be noncompliant (P < .0001). CONCLUSION We demonstrated that racial differences exist in oncology physicians' perceived barriers to GCT for patients with breast cancer. This nationwide survey will serve as a basis for understanding physicians' determinants of GCT for African American women and highlights the necessity of education and interventions to address bias among physicians. Awareness of such physician biases can enable further work to address inequities, ultimately leading to improved GCT equity for African American women with breast cancer. MDs self-reported practices on genetic testing for Blacks with breast cancer are not consistent with literature
Titin (TTN): from molecule to modifications, mechanics, and medical significance

Abstract The giant sarcomere protein titin is a major determinant of cardiomyocyte stiffness and contributor to cardiac strain sensing. Titin-based forces are highly regulated in health and disease, which aids in the regulation of myocardial function, including cardiac filling and output. Due to the enormous size, complexity, and malleability of the titin molecule, titin properties are also vulnerable to dysregulation, as observed in various cardiac disorders. This review provides an overview of how cardiac titin properties can be changed at a molecular level, including the role isoform diversity and post-translational modifications (acetylation, oxidation, and phosphorylation) play in regulating myocardial stiffness and contractility. We then consider how this regulation becomes unbalanced in heart disease, with an emphasis on changes in titin stiffness and protein quality control. In this context, new insights into the key pathomechanisms of human cardiomyopathy due to a truncation in the titin gene (TTN) are discussed. Along the way, we touch on the potential for titin to be therapeutically targeted to treat acquired or inherited cardiac conditions, such as HFpEF or TTN-truncation cardiomyopathy.
The mitochondrial DNA control region sequences from the Chinese sui population of southwestern China

Abstract Background Sui people are officially recognised people living in southwest China, but there has been a lack of genetic research, especially based on mitochondrial DNA data. Aim To study the sequences and haplogroups of the mitochondrial DNA control region in a typical Sui population, with the aim of helping to promote the establishment of a forensic DNA analysis reference database in East Asia. Subjects and methods We analysed 201 Sui individuals and observed the sequences of the mitochondrial DNA control region. We calculated and explained the haplotype frequencies, haplogroup distribution and pairwise Fst values between the Sui and 47 other populations in the world, in order to explore genetic polymorphisms and population relationships. Results 161 haplotypes were found in the Sui population, with frequencies of 0.0049–0.0199. All samples were assigned to 80 different haplogroups. The haplotype diversity and random matching probability were 0.999938 and 0.024729, respectively. The pairwise Fst values and correlation p-values of 48 populations showed that the Sui population was most closely related to the Miao population in Guizhou and the Han population in Henan, and closer to the Punjab population and Pukhtunkhwa population in Pakistan, and was significantly different from the other 43 groups. Compared with the other 43 groups, it is relatively isolated. Conclusion Our results show that the study of mitochondrial DNA based on the analysis of matrilineal genetic structure of the Sui population can help to promote the establishment of a forensic DNA reference database in East Asia and provide reference for future anthropological research.
The Global Configuration of Visual Stimuli Alters Co-Fluctuations of Cross-Hemispheric Human Brain Activity

We tested how a stimulus gestalt, defined by the neuronal interaction between local and global features of a stimulus, is represented within human primary visual cortex (V1). We used high-resolution fMRI, which serves as a surrogate of neuronal activation, to measure co-fluctuations within subregions of V1 as (male and female) subjects were presented with peripheral stimuli, each with different global configurations. We found stronger cross-hemisphere correlations when fine-scale V1 cortical subregions represented parts of the same object compared with different objects. This result was consistent with the vertical bias in global processing and, critically, was independent of the task and local discontinuities within objects. Thus, despite the relatively small receptive fields of neurons within V1, global stimulus configuration affects neuronal processing via correlated fluctuations between regions that represent different sectors of the visual field. SIGNIFICANCE STATEMENT We provide the first evidence for the impact of global stimulus configuration on cross-hemispheric fMRI fluctuations, measured in human primary visual cortex. Our results are consistent with changes in the level of γ-band synchrony, which has been shown to be affected by global stimulus configuration, being reflected in the level fMRI co-fluctuations. These data help narrow the gap between knowledge of global stimulus configuration encoding at the single-neuron level versus at the behavioral level.
Taenia solium Metacestode Factor as Probable Cause of Temporal Lobe Epilepsy

ABSTRACT. This article analyzes data from scientific publications (mainly reviews) concerning the link between human neurocysticercosis and epilepsy. Along with data from our own studies on experimental hippocampal sclerosis induced by a Taenia crassiceps metacestode factor in mice, it explores the connection between mechanisms that likely favor the development of epilepsy in cases of human neurocysticercosis. The data from both sources suggest the idea that the T. solium metacestode factor causes hippocampal sclerosis and later epilepsy in humans with neurocysticercosis.
Role of Nectin‑4 protein in cancer (Review).

The Nectin cell adhesion molecule (Nectin) family members are Ca2+‑independent immunoglobulin‑like cellular adhesion molecules (including Nectins 1‑4), involved in cell adhesion via homophilic/heterophilic interplay. In addition, the Nectin family plays a significant role in enhancing cellular viability and movement ability. In contrast to enrichment of Nectins 1‑3 in normal tissues, Nectin‑4 is particularly overexpressed in a number of tumor types, including breast, lung, urothelial, colorectal, pancreatic and ovarian cancer. Moreover, the upregulation of Nectin‑4 is an independent biomarker for overall survival in numerous cancer types. A large number of studies have revealed that high expression of Nectin‑4 is closely related to tumor occurrence and development in various cancer types, but the manner in which Nectin‑4 protein contributes to the onset and development of these malignancies is yet unknown. The present review summarizes the molecular mechanisms and functions of Nectin‑4 protein in the biological processes and current advances with regard to its expression and regulation in various cancer types.
Increased levels of soluble fms‐like tyrosine kinase‐1 are associated with adverse outcome in pregnant women with COVID‐19

In addition to the lungs, the placenta and the endothelium can be affected by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF) are markers of endothelial dysfunction and could potentially serve as predictors of severe coronavirus disease 2019 (COVID‐19). We aimed to investigate the association of serum concentrations of sFlt‐1 and PlGF with the severity of COVID‐19 in pregnancy.
Brain Cancer Drug Discovery: Clinical Trials, Drug Classes, Targets, and Combinatorial Therapies

Brain cancer is a formidable challenge for drug development, and drugs derived from many cutting-edge technologies are being tested in clinical trials. We manually characterized 981 clinical trials on brain tumors that were registered in ClinicalTrials.gov from 2010 to 2020. We identified 582 unique therapeutic entities targeting 581 unique drug targets and 557 unique treatment combinations involving drugs. We performed the classification of both the drugs and drug targets based on pharmacological and structural classifications. Our analysis demonstrates a large diversity of agents and targets. Currently, we identified 32 different pharmacological directions for therapies that are based on 42 structural classes of agents. Our analysis shows that kinase inhibitors, chemotherapeutic agents, and cancer vaccines are the three most common classes of agents identified in trials. Agents in clinical trials demonstrated uneven distribution in combination approaches; chemotherapy agents, proteasome inhibitors, and immune modulators frequently appeared in combinations, whereas kinase inhibitors, modified immune effector cells did not as was shown by combination networks and descriptive statistics. This analysis provides an extensive overview of the drug discovery field in brain cancer, shifts that have been happening in recent years, and challenges that are likely to come. Significance Statement This review provides comprehensive quantitative analysis and discussion of the brain cancer drug discovery field, including classification of drug, targets, and therapies.