Miracle-dz/UniFAR-FTUs huggingface dataset:
Compressed sensorimotor-to-transmodal hierarchical organization in schizophrenia

Abstract Background Schizophrenia has been primarily conceptualized as a disorder of high-order cognitive functions with deficits in executive brain regions. Yet due to the increasing reports of early sensory processing deficit, recent models focus more on the developmental effects of impaired sensory process on high-order functions. The present study examined whether this pathological interaction relates to an overarching system-level imbalance, specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks. Methods We applied a novel combination of connectome gradient and stepwise connectivity analysis to resting-state fMRI to characterize the sensorimotor-to-transmodal cortical hierarchy organization (96 patients v. 122 controls). Results We demonstrated compression of the cortical hierarchy organization in schizophrenia, with a prominent compression from the sensorimotor region and a less prominent compression from the frontal−parietal region, resulting in a diminished separation between sensory and fronto-parietal cognitive systems. Further analyses suggested reduced differentiation related to atypical functional connectome transition from unimodal to transmodal brain areas. Specifically, we found hypo-connectivity within unimodal regions and hyper-connectivity between unimodal regions and fronto-parietal and ventral attention regions along the classical sensation-to-cognition continuum (voxel-level corrected, p < 0.05). Conclusions The compression of cortical hierarchy organization represents a novel and integrative system-level substrate underlying the pathological interaction of early sensory and cognitive function in schizophrenia. This abnormal cortical hierarchy organization suggests cascading impairments from the disruption of the somatosensory−motor system and inefficient integration of bottom-up sensory information with attentional demands and executive control processes partially account for high-level cognitive deficits characteristic of schizophrenia.
Quercetin prevents isoprenaline-induced myocardial fibrosis by promoting autophagy via regulating miR-223-3p/FOXO3

ABSTRACT Atrial fibrillation (AF) is the common arrhythmias. Myocardial fibrosis (MF) is closely related to atrial remodeling and leads to AF. MF is the main cause of cardiovascular diseases and a pathological basis of AF. Thus, the underlying mechanism in MF and AF development should be fully elucidated for AF therapeutic innovation. Autophagy is a highly conserved lysosomal degradation pathway, and the relationship between autophagy and MF has been previously shown. Moreover, research reported that quercetin (Que) could ameliorate MF. The current study aimed to explore the mechanism of Que in MF. The results in this study showed that in clinical AF patients and in aged rats, miR-223-3p was high-expressed, while FOXO3 and autophagy pathway related proteins, such as ATG7, p62/SQSTM1 and the ratio of LC3B-II/LC3B-I were significantly inhibited. In vivo and in vitro studies, we found that Que can effectively inhibit the expression of miR-223-3p in AF model cells and rats myocardial tissues, and meanwhile enhance the expression of FOXO3 and activate the autophagy pathway, and significantly inhibit myocardial fibrosis, and improve myocardial remodeling in atrial fibrillation. All in all, in this study, we found that Que prevents isoprenaline-induced MF by increasing autophagy via regulating miR-223-3p/FOXO3.
Neural cell adhesion molecule is required for ventricular conduction system development

ABSTRACT The most distal portion of the ventricular conduction system (VCS) contains cardiac Purkinje cells (PCs), which are essential for synchronous activation of the ventricular myocardium. Contactin-2 (CNTN2), a member of the immunoglobulin superfamily of cell adhesion molecules (IgSF-CAMs), was previously identified as a marker of the VCS. Through differential transcriptional profiling, we discovered two additional highly enriched IgSF-CAMs in the VCS: NCAM-1 and ALCAM. Immunofluorescence staining showed dynamic expression patterns for each IgSF-CAM during embryonic and early postnatal stages, but ultimately all three proteins became highly enriched in mature PCs. Mice deficient in NCAM-1, but not CNTN2 or ALCAM, exhibited defects in PC gene expression and VCS patterning, as well as cardiac conduction disease. Moreover, using ST8sia2 and ST8sia4 knockout mice, we show that inhibition of post-translational modification of NCAM-1 by polysialic acid leads to disrupted trafficking of sarcolemmal intercalated disc proteins to junctional membranes and abnormal expansion of the extracellular space between apposing PCs. Taken together, our data provide insights into the complex developmental biology of the ventricular conduction system.
Shift working and cardiovascular health

ABSTRACT Adequate sleep is an important component of cardiovascular health. Due to circadian misalignment and irregular shifts, inadequate sleep is common in shift workers. Adverse consequences include daytime sleepiness, decreased cognitive performance, increased sympathetic tone, inflammation, impaired glucose tolerance, and altered leptin and ghrelin levels. When circadian adjustment has not occurred, daytime sleepers often experience decreased sleep duration and increased wakefulness during displaced sleep; additionally, skipping sleep is common in shift workers, further contributing to sleep deprivation. Habitual decreased sleep duration and physiological changes contribute to obesity, diabetes, hypertension, and increased cardiovascular disease risk in shift workers. Shift workers with obstructive sleep apnea (OSA), the most common sleep-related breathing disorder, can experience more frequent sleep disruptions than non-shift workers with OSA. Furthermore, shift work-induced circadian misalignment may potentiate cardiometabolic risk in OSA patients through autonomic nervous system dysfunction and other mechanisms.
MICAL-L1 is required for cargo protein delivery to the cell surface

ABSTRACT Secreted proteins are transported along intracellular route from the endoplasmic reticulum through the Golgi before reaching the plasma membrane. Small GTPase Rab and their effectors play a key role in membrane trafficking. Using confocal microscopy, we showed that MICAL-L1 was associated with tubulo-vesicular structures and exhibited a significant colocalization with markers of the Golgi apparatus and recycling endosomes. Super resolution STORM microscopy suggested at the molecular level, a very close association of MICAL-L1 and microdomains in the Golgi cisternae. Using a synchronized secretion assay, we report that the shRNA-mediated depletion of MICAL-L1 impaired the delivery of a subset of cargo proteins to the cell surface. The process of membrane tubulation was monitored in vitro, and we observe that recombinant MICAL-L1-RBD domain may contribute to promote PACSINs-mediated membrane tubulation. Interestingly, two hydrophobic residues at the C-terminus of MICAL-L1 appeared to be important for phosphatidic acid binding, and for association with membrane tubules. Our results reveal a new role for MICAL-L1 in cargo delivery to the plasma membrane.
Moving Pharmacogenetics Into Practice: It’s All About the Evidence!

The evidence for pharmacogenetics has grown rapidly in recent decades. However, the strength of evidence required for the clinical implementation of pharmacogenetics is highly debated. Therefore, the purpose of this review is to summarize different perspectives on the evidence required for the clinical implementation of pharmacogenetics. First, we present two patient cases that demonstrate how knowledge of pharmacogenetic evidence affected their care. Then we summarize resources that curate pharmacogenetic evidence, types of evidence (with an emphasis on randomized controlled trials [RCT]) and their limitations, and different perspectives from implementers, clinicians, and patients. We compare pharmacogenetics to a historical example (i.e., the evidence required for the clinical implementation of pharmacokinetics/therapeutic drug monitoring), and we provide future perspectives on the evidence for pharmacogenetic panels and the need for more education in addition to evidence. Although there are differences in the interpretation of pharmacogenetic evidence across resources, efforts for standardization are underway. Survey data illustrate the value of pharmacogenetic testing from the patient perspective, with their providers seen as key to ensuring maximum benefit from test results. However, clinicians and practice guidelines from medical societies often rely on RCT data to guide treatment decisions, which are not always feasible or ethical in pharmacogenetics. Thus, recognition of other types of evidence to support pharmacogenetic implementation is needed. Among pharmacogenetic implementers, consistent evidence of pharmacogenetic associations is deemed most critical. Ultimately, moving pharmacogenetics into practice will require consideration of multiple stakeholder perspectives, keeping particularly attuned to the voice of the ultimate stakeholder—the patient.
Techniques used to assess intussusceptive angiogenesis: A systematic review

Intussusceptive angiogenesis (IA) is an important physiological form of angiogenesis in which an existing vessel splits in two by the formation of an intraluminal tissue pillar. The presence of these intraluminal pillars form the hallmark of ongoing IA in growing vascular beds. However, their visualization is technically challenging. The goal of this systematic review was to investigate which techniques are being used to identify intraluminal pillars and to formulate important points to keep in mind when studying IA. A systematic literature search resulted in 154 evaluated articles of which the majority (65%) provided sufficient data to unambiguously demonstrate the presence of intraluminal pillars. Scanning electron microscopy imaging of vascular corrosion casts and serial sectioning of ultrathin sections are the most used techniques. New methods such as serial block face scanning electron microscopy and micro computed tomography (μCT) are gaining importance. Moreover, our results indicate that IA was studied in a variety of animals and tissues. IA is a biologically very relevant form of angiogenesis. Techniques to visualize intraluminal pillars need to have a minimal resolution of 1 μm and should provide information on the 3D‐nature of the pillars. Optimally, several techniques are combined to demonstrate ongoing IA.
Neat1 decreases neuronal apoptosis after oxygen and glucose deprivation

Studies have shown that downregulation of nuclear-enriched autosomal transcript 1 (Neat1) may adversely affect the recovery of nerve function and the increased loss of hippocampal neurons in mice. Whether Neat1 has protective or inhibitory effects on neuronal cell apoptosis after secondary brain injury remains unclear. Therefore, the effects of Neat1 on neuronal apoptosis were observed. C57BL/6 primary neurons were obtained from the cortices of newborn mice and cultured in vitro, and an oxygen and glucose deprivation cell model was established to simulate the secondary brain injury that occurs after traumatic brain injury in vitro. The level of Neat1 expression in neuronal cells was regulated by constructing a recombinant adenovirus to infect neurons, and the effects of Neat1 expression on neuronal apoptosis after oxygen and glucose deprivation were observed. The experiment was divided into four groups: the control group, without any treatment, received normal culture; the oxygen and glucose deprivation group were subjected to the oxygen and glucose deprivation model protocol; the Neat1 overexpression and Neat1 downregulation groups were treated with Neat1 expression intervention techniques and were subjected to the in oxygen and glucose deprivation protocol. The protein expression levels of neurons p53-induced death domain protein 1 (PIDD1, a pro-apoptotic protein), caspase-2 (an apoptotic priming protein), cytochrome C (a pro-apoptotic protein), and cleaved caspase-3 (an apoptotic executive protein) were measured in each group using the western blot assay. To observe changes in the intracellular distribution of cytochrome C, the expression levels of cytochrome C in the cytoplasm and mitochondria of neurons from each group were detected by western blot assay. Differences in the cell viability and apoptosis rate between groups were detected by cell-counting kit 8 assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, respectively. The results showed that the apoptosis rate, PIDD1, caspase-2, and cleaved caspase-3 expression levels significantly decreased, and cell viability significantly improved in the Neat1 overexpression group compared with the oxygen and glucose deprivation group; however, Neat1 downregulation reversed these changes. Compared with the Neat1 downregulation group, the cytosolic cytochrome C level in the Neat1 overexpression group significantly decreased, and the mitochondrial cytochrome C level significantly increased. These data indicate that Neat1 upregulation can reduce the release of cytochrome C from the mitochondria to the cytoplasm by inhibiting the PIDD1-caspase-2 pathway, reducing the activation of caspase-3, and preventing neuronal apoptosis after oxygen and glucose deprivation, which might reduce secondary brain injury after traumatic brain injury. All experiments were approved by the Animal Ethics Committee of the First Affiliated Hospital of Chongqing Medical University, China, on December 19, 2020 (approval No. 2020-895).
Retraction

Retraction: “Knockdown of long noncoding RNA GAS5 attenuates H2O2‐induced damage in retinal ganglion cells through upregulating miR‐124: Potential role in traumatic brain injury,” by Xinglu Miao, Anran Liang, J Cell Biochem. 2019; 2313‐2322: The above article, published online on 18 November 2018 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.27560), has been retracted by agreement between the the journal's Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC.
The complete chloroplast genome of Tetrastigma planicaule, one important folk medicinal plant in China

Abstract We announce here the first complete chloroplast genome sequence of Tetrastigma planicaule, one important Chinese folk medicinal plant. This complete chloroplast genome is 160,323 bp in length. In total, 131 genes were identified, including 86 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The results of phylogenetic analysis indicated that Tetrastigma is a separate genus and is closely related to Vitis.
Current Perspectives on the Systemic Management of Atopic Dermatitis

Abstract Atopic dermatitis (AD) is a common disease of childhood, and some patients experience a prolonged clinical course into adolescence and adulthood. Systemic management is required when AD is not adequately controlled with topical medications. Our aim is to provide a comprehensive review of commonly used systemic immunomodulating agents in childhood and adult AD, including cyclosporine A (CsA), azathioprine (AZA), methotrexate (MTX) and mycophenolate mofetil (MMF), which are prescribed off-label in the United States, as well as dupilumab, an FDA-approved biologic. We will also provide a brief overview of emerging systemic therapies currently under investigation.
Scutellaria barbata D. Don Polysaccharides Inhibit High Glucose-Induced Proliferation and Angiogenesis of Retinal Vascular Endothelial Cells

Purpose The traditional Chinese medicine Scutellaria barbata D. Don (S. barbata) has been reported to exhibit anti-cancer and anti-inflammation activities. The ethanol extract of S. barbata has been confirmed to attenuate diabetic retinopathy (DR). This study aimed to investigate the effects and underlying mechanisms of the polysaccharides isolated from S. barbata (PSB) on the proliferation and angiogenesis of retinal vascular endothelial cells (RVECs) in DR. Methods Human RVECs (HRVECs) were cultured in normal glucose (NG, 5.5 mM), mannitol (MA, 30 mM), high glucose (HG, 30 mM) and HG plus 40 μg/mL PSB, respectively. Then, cell proliferation, migration and angiogenesis were evaluated. The cell proliferation was also estimated in the presence of SLIGKV, which was used to induce the phosphorylation of ERK (p-ERK). Results PSB reduced normal and HG-induced HRVECs cell viability in a concentration-dependent manner. The protein expression of proliferating cell nuclear antigen (PCNA) and proliferating antigen KI67 (Ki67), the migration rate and tube formation ability, which were increased by HG treatment, were significantly decreased by PSB. PSB also inhibited the phosphorylation of Raf, MEK and ERK in HG-stimulated HRVECs. Moreover, the application of SLIGKV recovered cell viability and the expression of p-ERK, PCNA and Ki67, in HG plus PSB-treated cells. Finally, the HG-enhanced expression of VE-cadherin, Frizzed, β-catenin, MMP-2 and MMP-9 was all reversed by PSB. Conclusion PSB could inhibit HG-induced HRVECs proliferation, migration and neovascularization, and these effects might work through blocking the activation of MEK/ERK pathway and VEGF/VE-cadherin axis.
COVID-19 and Male Sexual Functioning: A report of 3 Recovered Cases and Literature Review

COVID-19 is a new global pandemic. It can affect multiple body systems and functions. However, the relationship between COVID-19 and male sexual activity did not yet get much consideration. Herein, we report the impact of COVID-19 on sexual function in 3 men who recovered from the disease. Compared with their condition before catching the infection, the men showed, in different degrees, a decline in all aspects of sexual function as assessed by the international index of erectile function. They started to develop premature ejaculation or exacerbate an already existing condition according to the premature ejaculation diagnostic tool scoring. Beck’s depression inventory revealed deterioration of the men’s moods up to severe depression. The sex-related hormones (testosterone-total and free, luteinizing hormone, follicle-stimulating hormone, prolactin, and estradiol) of these men were within normal levels. To the best of our knowledge, this is the first case report documenting deleterious changes in mood and several aspects of sexual functioning in males after recovery from the COVID-19 using validated measurement tools. Follow-up and psychological support of the recovered men may help mend their moods and consequently upgrade their sexual functioning.
A 5-Year Retrospective Analysis of Raoultella planticola Bacteriuria

Introduction Raoultella planticola is an aerobic gram-negative rod predominantly found in soil and aquatic environments. The typical reservoirs of Raoultella spp. include the gastrointestinal tract and the upper respiratory tract. It usually causes pneumonia, biliary tract infections, and bacteremia. Urinary tract infection (UTI) secondary to R. planticola is an uncommon entity. Less than 10 cases of R. planticola-associated UTIs in adults have been published in the literature to date. Objective This is a single institution retrospective study undertaken to identify the epidemiology, patient characteristics, clinical spectrum, predisposing risk factors and the outcome of patients with UTI caused by R. planticola. Results A total of 37 R. planticola isolates were identified in urine samples over a 5-year study period. The mean age of the patient population was 77 years. The most common comorbidity was diabetes mellitus, which was present in 16 patients. Only 3 patients had a history of steroid use, an immunosuppressive condition, or were on chemotherapy. The most common presenting complaint was altered mental status followed by fever. Resistance to ampicillin was found in 35 isolates which seems to be an intrinsic characteristic of Raoultella spp. and 2 isolates were multidrug-resistant, but still susceptible to ciprofloxacin. The average length of stay was 3 days, and the average duration of antibiotic administration was 8 days. Ciprofloxacin was the most frequently prescribed antibiotic (9 patients). The severity of infection ranged from simple cystitis in 15 patients to urosepsis in 2 patients and septic shock in 2 patients. There were no mortalities in our cohort. Conclusion Our study revealed that patients with R. planticola UTI had higher proportion of diabetes mellitus, renal failure compared to the general population. Our study also confirms the intrinsic resistance to ampicillin of Raoultella spp. , which has been documented previously in the literature.
Linguistic-Cognitive Outcomes in Children with Acute Lymphoid Leukemia: An Exploratory Study

Background Acute lymphoid leukemia (ALL) is the most prevalent cancer of childhood. Impairment in linguistic and memory skills is a possible late sequela in cancer survivors that can limit their quality of life and the overall performance of the individual in society. There is evidence that survivors of ALL treated exclusively with chemotherapy demonstrate significant differences in long-term linguistic and memory functions and also changes in neuroanatomical integrity. However, most studies described do not count on a speech-language pathologist in their team, which we consider important to discuss. Thus, the objective of the present study was to assess memory and vocabulary skills in the pediatric population diagnosed with acute lymphoid leukemia during chemotherapy treatment. Materials and Methods An observational cohort study was conducted over a 1.8-year period. Participants of this research were children diagnosed with ALL. All participants were assessed on their linguistic-cognitive skills (ie, vocabulary, short-term memory and lexical access). All data underwent statistical analyses. Results The results of the current study found no major significant difference in the linguistic-cognitive performance of children with ALL and their healthy controls. Regarding the linguistic variables, we believe that there should be a differentiation between the effects of the drugs and the effects of social communication skills on performance. Conclusion This first characterization of the linguistic-cognitive abilities of children with ALL did not identify differences between these children and their healthy peers, although we were able to identify variables regarding the multidisciplinary team and social communication that should be considered in future studies.