Miracle-dz/UniFAR-FTUs huggingface dataset:
The Density of Perineuronal Nets Increases With Age in the Inferior Colliculus in the Fischer Brown Norway Rat

Age-related hearing loss, one of the most frequently diagnosed disabilities in industrialized countries, may result from declining levels of GABA in the aging inferior colliculus (IC). However, the mechanisms of aging and subsequent disruptions of temporal processing in elderly hearing abilities are still being investigated. Perineuronal nets (PNs) are a specialized form of the extracellular matrix and have been linked to GABAergic neurotransmission and to the regulation of structural and synaptic plasticity. We sought to determine whether the density of PNs in the IC changes with age. We combined Wisteria floribunda agglutinin (WFA) staining with immunohistochemistry to glutamic acid decarboxylase in three age groups of Fischer Brown Norway (FBN) rats. The density of PNs on GABAergic and non-GABAergic cells in the three major subdivisions of the IC was quantified. Results first demonstrate that the density of PNs in the FBN IC increase with age. The greatest increases of PN density from young to old age occurred in the central IC (67% increase) and dorsal IC (117% increase). Second, in the young IC, PNs surround non-GABAergic and GABAergic cells with the majority of PNs surrounding the former. The increase of PNs with age in the IC occurred on both non-GABAergic and GABAergic populations. The average density of PN-surrounded non-GABAergic cells increased from 84.9 PNs/mm2 in the young to 134.2 PNs/mm2 in the old. While the density of PN-surrounded GABAergic cells increased from 26 PNs/mm2 in the young to 40.6 PNs/mm2 in the old. The causality is unclear, but increases in PN density in old age may play a role in altered auditory processing in the elderly, or may lead to further changes in IC plasticity.
Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease.

PURPOSE OF REVIEW Several mutations in the apolipoprotein (apo) B, proprotein convertase subtilisin kexin 9 (PCSK9) and microsomal triglyceride transfer protein genes result in low or absent levels of apoB and LDL cholesterol (LDL-C) in plasma which cause familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia (ABL). Mutations in the angiopoietin-like protein 3 ANGPTL3 gene cause familial combined hypolipidemia (FHBL2). Clinical manifestations range from none-to-severe, debilitating and life-threatening disorders. This review summarizes recent genetic, metabolic and clinical findings and management strategies. RECENT FINDINGS Fatty liver, cirrhosis and hepatocellular carcinoma have been reported in FHBL and ABL probably due to decreased triglyceride export from the liver. Loss of function mutations in PCSK-9 and ANGPTL3 cause FHBL but not hepatic steatosis. In 12 case-control studies with 57 973 individuals, an apoB truncation was associated with a 72% reduction in coronary heart disease (odds ratio, 0.28; 95% confidence interval, 0.12-0.64; P = 0.002). PCSK9 inhibitors lowered risk of cardiovascular events in large, randomized trials without apparent adverse sequelae. SUMMARY Mutations causing low LDL-C and apoB have provided insight into lipid metabolism, disease associations and the basis for drug development to lower LDL-C in disorders causing high levels of cholesterol. Early diagnosis and treatment is necessary to prevent adverse sequelae from FHBL and ABL.
A Nomogram and a Risk Classification System Predicting the Cancer-Specific Survival of Patients with Initially-Diagnosed Osseous Spinal and Pelvic Tumors.

STUDY DESIGN. Retrospective analysis. OBJECTIVE. Our goal was to provide a predictive model and a risk classification system that predicts cancer-specific survival (CSS) from spinal bone tumors. SUMMARY OF BACKGROUND DATA Primary bone tumors of the spine are rare, thus limiting the understanding of the manifestations and survival from these tumors. Nomograms are the graphical representation of mathematical relationships or laws that accurately predict individual survival. METHODS A total of 1033 patients with spinal bone tumors between 2004 and 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox analysis were used on the training set to select significant predictors to build a nomogram that predicted 3- and 5-year CSS. We validate the precision of the nomogram by discrimination and calibration, and the clinical value of nomogram was assessed by making use of a decision curve analyses (DCA). RESULTS Data from 1033 patients with initially-diagnosed spinal bone tumors were extracted from the SEER database. Multivariate analysis of the training cohort, predictors included in the nomogram were age, pathological type, tumor stage, and surgery. The value of C-index was 0.711 and 0.743 for the internal and external validation sets, respectively, indicating good agreement with actual CSS. The internal and external calibration curves revealed good correlation of CSS between the actual observation and the nomogram. Then, the DCA showed greater net benefits than that of treat-all or treat-none at all time points. A novel risk grouping system was established for CSS that can readily divide all patients into three distinct risk groups. CONCLUSIONS The proposed nomogram obtained more precision prognostic prediction for patients with initially-diagnosed primary spinal bone tumors. LEVEL OF EVIDENCE 3.
Is time since vasectomy more important as prognostic factor for pregnancy and live birth than female and laboratory variables when treating vasectomised man using ICSI?

Fatherhood after vasectomy can be done by vasectomy reversal or intracytoplasmic sperm injection (ICSI). Time since vasectomy is the best predictive factor for patency and live birth after a vasectomy reversal but has uncertain importance after ICSI with sperm retrieval. The present study examines the influence of male, female and laboratory variables on pregnancy and live birth. The study is based on 450 ICSI cycles from 332 patients performed on three infertility centres between 1994 and 2012. Interval time since vasectomy was divided in four groups GI—less than 3 years (n = 02); GII—3 to 8 years (n = 74); GIII—9 to 14 years (n = 161) and GIV—15 or more years (n = 213). The variables were tested for pregnancy rate and live birth for first and repeated cycles. Pregnancy and live birth rate were not statistically different among the study interval time groups for first or repeated cycles. Female and laboratory variables were statistically different for couples with pregnancy and live birth for the first cycles. The study suggests that variables coming from female and laboratory were more important than time since vasectomy when treating man with vasectomy using ICSI with sperm retrieval.
Temporal dynamics of real-world emotion are more strongly linked to prediction error than outcome.

Primarily based on laboratory studies, theories of affect propose that emotions are driven by the valence of outcomes as well as the difference between the outcome itself and the expected outcome (i.e., the prediction error [PE]). Yet no work has assessed the drivers of emotion using real-world, personally meaningful events on timescales over which human emotion unfolds. We developed an event-triggered, ecological momentary assessment procedure measuring positive and negative affect (PA and NA, respectively) in university students as they received exam grades for which they had made predictions. We split data into exploratory and confirmatory samples, and built computational models predicting the time course of PA and NA and demonstrate that a model incorporating both exam grade and grade PE accounted for the time course of PA and NA better than a model solely using exam grades. Further, grade PEs were stronger predictors of the time course of PA and NA than the grades themselves. Similarly, the effects of PEs also persisted longer for NA than PA. These data indicate that deviations from expectations are critical determinants of the temporal dynamics of real-world emotion. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Combination immune checkpoint inhibitors with platinum-based chemotherapy in advanced non-small cell lung cancer: what's known and what's next.

Immune checkpoint inhibitors (ICIs) that target programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have revolutionized the treatment paradigm for patients with advanced or metastatic non-small cell lung cancer (NSCLC) (1). Yet, only a minority of patients could derive clinical benefit from anti-PD-1/PD-L1 antibody monotherapy (2). Both scientists and physicians aimed to enhance the therapeutic efficacy and expand benefit populations via investigating the rational combination therapeutic strategies and predictive biomarkers (2-6). Since chemotherapy could elicit anticancer immunity via release of potentially immunogenic tumor antigens (7,8), combination of anti-PD-1/PD-L1 antibodies with chemotherapy is one of the most anticipated strategy in this field.
Family aggression and attachment avoidance influence neuroendocrine reactivity in young adult couples.

Family-of-origin aggression (FOA) exposure is a chronic childhood stressor that has been linked to altered stress reactivity of the hypothalamic-pituitary-adrenal (HPA) axis in adulthood. The effects of FOA also spill over between partners in romantic couples, such that one partner's FOA history influences the other's HPA reactivity during couple interactions. However, the direction of these effects is inconsistent, with both heightened and blunted HPA reactivity observed; this heterogeneity suggests the presence of moderators. This study measured HPA reactivity during emotionally vulnerable conversations between young adult romantic partners to assess whether romantic attachment avoidance accounts for this divergence by moderating actor and partner effects of FOA on HPA. A total of 112 opposite-sex couples (224 young adults) provided information on FOA and avoidance, completed dyadic interaction procedures, and provided saliva samples to assess HPA reactivity during interactions. Multilevel structural equation models revealed that FOA did not predict either the actor's or the partner's HPA reactivity. However, FOA and avoidance interacted to produce both actor and partner effects, such that greater FOA exposure heightened HPA reactivity when avoidance was high but blunted reactivity when avoidance was low. The results support the conjecture that proximal relationship-related characteristics, such as attachment avoidance, influence whether distal relationship-related stressors, such as FOA, amplify or attenuate physiological reactivity during emotionally vulnerable interactions. Because HPA reactivity has been linked to a variety of health outcomes, identifying relationship-related buffers of associations between FOA and HPA response may inform future interventions to protect health for FOA-exposed youth. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer.

Author(s): Gupta, Samir; Lieberman, David; Anderson, Joseph C; Burke, Carol A; Dominitz, Jason A; Kaltenbach, Tonya; Robertson, Douglas J; Shaukat, Aasma; Syngal, Sapna; Rex, Douglas K | Abstract: Colonoscopy is routinely performed for colorectal cancer (CRC) screening, follow-up of other abnormal screening tests, work up of signs and symptoms of gastrointestinal disease, and surveillance after CRC and polyp removal. Post procedure, colonoscopists are expected to provide follow-up recommendations to patients and referring physicians. Recommendations for follow-up after normal colonoscopy among individuals age-eligible for screening, and post-polypectomy among all individuals with polyps are among the most common clinical scenarios requiring guidance1.Risk of metachronous advanced neoplasia is associated with findings on prior colonoscopy. After high quality colonoscopy, patients with no neoplasia detected are at the lowest risk, and those with polyps are risk stratified based on the histology, number, location, and size of polyps detected. Since release of the last US Multi-Society Task Force (Task Force) recommendations for post colonoscopy follow-up and polyp surveillance in 20122, a number of papers have been published on risk of CRC based on colonoscopy findings and patient characteristics, as well as the potential impact of screening and surveillance colonoscopy on outcomes such as incident CRC and polyps. Further, recent studies increasingly reflect the modern era of colonoscopy with more awareness of the importance of quality factors (e.g. adequate bowel preparation, cecal intubation, adequate adenoma detection, complete polyp resection), and utilization of state of the art technologies (e.g. high definition colonoscopes). Higher quality colonoscopy could impact the importance of previously identified risk factors. Our aim was to review newly available evidence and update recommendations for follow-up after colonoscopy with or without polypectomy.Keywords: aftercare, colon polyps, colonoscopy, colon cancer, consensus statement, early detection of cancer, practice guideline
Frequency and Severity of Autonomic Symptoms in Idiopathic Hypersomnia.

STUDY OBJECTIVES We aimed to quantify the symptoms of autonomic nervous system (ANS) dysfunction in a large online cohort of patients with IH, and to determine how the severity of these symptoms interacts with sleepiness, fatigue, and quality of life. METHODS One hundred thirty-eight IH patients and 81 age- and sex-matched controls were recruited through the website of the Hypersomnia Foundation, a U.S.-based patient advocacy group. Twenty-four confirmed IH patients were selected by the study investigators as a comparison group. All participants completed a battery of online sleep, autonomic, and quality of life questionnaires including the composite autonomic symptom score-31 (COMPASS-31). RESULTS Online and confirmed patients reported significantly higher COMPASS-31 scores (43.6 [33.6-52.7] & 32.9 [21.7- 46.8] vs. 17.6 [11.7-27.9], p<0.001), with the greatest symptom burden in the orthostatic and vasomotor domains. Online and confirmed patients reported more sleepiness (ESS), whereas only online patients reported more fatigue (CFQ). Both the ESS and CFQ positively correlated with COMPASS-31 scores. Patients reported lower quality of life as reflected by lower scores across all domains of the RAND-36, which was negatively correlated with COMPASS-31 scores. CONCLUSIONS Symptoms of ANS dysfunction are common in IH. In addition, ANS symptom burden was positively correlated with sleepiness and negatively correlated with quality of life.
Resveratrol Combined with 17β-Estradiol Prevents IL-1β Induced Apoptosis in Human Nucleus Pulposus Via The PI3K/AKT/Mtor and PI3K/AKT/GSK-3β Pathway

Abstract Backgrounds Nucleus pulposus (NP) apoptosis is mainly charged for the pathological process of Intervertebral disc degeneration (IVDD). Our previous study revealed that Resveratrol (RSV) combined with 17β-estradiol (E2) was more effective in cutting down IL-1β induced NP cell apoptosis via PI3K/AKT pathway. The present study further evaluated the effect of RSV and E2 in the anti-apoptosis process of IVDD. Methods Human nucleus pulposus (NP) cells culture system and IL-1β inducing apoptosis model were constructed in this research. RSV and E2 were used to inhibit apoptosis. FACS (Fluorescence-activated cell sorting) and CCK-8 (Cell Counting Kit-8) assays were respectively used to determine apoptotic incidence and cell viability of NP cells. Quantitative RT-PCR was used to determine expression of target genes in mRNA level, and western blot analysis was performed to detect the changes of related protein expression. Results RSV combined with E2 attenuated IL-1β-induced cell apoptosis and recovered cell viability. Blockers for mTOR and GSK-3β abated the effect of RSV and E2. RSV combined with E2 obviously increased activated P-mTOR and P-GSK-3β, which contributes to the downregulation of caspase-3. Activated P-NF-kappa B was not involved in the anti-apoptosis process of RSV and E2. Conclusion Combination of Resveratrol and 17β-estradiol efficiently resisted IL-1β induced apoptosis of NP cell, mainly through PI3K/AKT/mTOR/caspase-3 and PI3K/AKT/GSK-3β pathway.
miR‐382‐5p promotes porcine reproductive and respiratory syndrome virus (PRRSV) replication by negatively regulating the induction of type I interferon

Previous studies have indicated that inhibition of type I interferon production may be an important reason for porcine reproductive and respiratory syndrome virus (PRRSV) to achieve immune escape, revealing the mechanism of inhibiting the production of type I interferon will help design novel strategies for controlling PRRS. Here, we found that PRRSV infection upregulated the expression of miR‐382‐5p, which in turn inhibited polyI:C‐induced the production of type I interferon by targeting heat shock protein 60 (HSP60), thus facilitating PRRSV replication in MARC‐145 cells. Furthermore, we found that HSP60 could interact with mitochondrial antiviral signaling protein (MAVS), an important signal transduction protein for inducing production of type I interferon, and promote polyI:C‐mediated the production of type I interferon in a MAVS‐dependent manner. Finally, we also found that HSP60 could inhibit PRRSV replication in a MAVS‐dependent manner, which indicated that HSP60 was a novel antiviral protein against PRRSV replication. In conclusion, the study demonstrated that miR‐382‐5p was upregulated during PRRSV infection and may promote PRRSV replication by negatively regulating the production of type I interferon, which also indicated that miR‐382‐5p and HSP60 might be the potential therapeutic targets for anti‐PRRSV.
Using Finger Puppets in the Primary Care Setting to Support Caregivers Talking With Their Infants: A Feasibility Pilot Study

Disadvantaged children often show disparities in early language development. We tested the feasibility, acceptability, and preliminary efficacy of introducing finger puppets in the primary care setting at the 2-month well visit to support caregivers talking with their infants. Caregivers completed a sociodemographic survey and were contacted by phone 2 weeks later to assess initial usage and satisfaction. Ages & Stages Questionnaires (ASQ-3) were independently recorded at well visits. A family cumulative risk score was calculated from the sociodemographic survey. Thirty-four caregiver-child pairs were enrolled. Caregivers reported high satisfaction with the intervention. ASQ-3 Communication and Total scores at 6, 12, and 18 months were significantly higher for high puppet users across all age levels with no significant interactions with age or cumulative risk. Finger puppets provide a low-cost way to promote language-rich interactions. Preliminary evidence suggests that high puppet usage may have long-lasting effects on child development and should be further evaluated.
Mechanisms for cellular uptake of nanosized clinical MRI contrast agents

Abstract Engineered Nanomaterials (NMs), such as Superparamagnetic Iron Oxide Nanoparticles (SPIONs), offer significant benefits in a wide range of applications, including cancer diagnostic and therapeutic strategies. However, the use of NMs in biomedicine raises safety concerns due to lack of knowledge on possible biological interactions and effects. The initial basis for using SPIONs as biomedical MRI contrast enhancement agents was the idea that they are selectively taken up by macrophage cells, and not by the surrounding cancer cells. To investigate this claim, we analyzed the uptake of SPIONs into well-established cancer cell models and benchmarked this against a common macrophage cell model. In combination with fluorescent labeling of compartments and siRNA silencing of various proteins involved in common endocytic pathways, the mechanisms of internalization of SPIONs in these cell types has been ascertained utilizing reflectance confocal microscopy. Caveolar mediated endocytosis and macropinocytosis are both implicated in SPION uptake into cancer cells, whereas in macrophage cells, a clathrin-dependant route appears to predominate. Colocalization studies confirmed the eventual fate of SPIONs as accumulation in the degradative lysosomes. Dissolution of the SPIONs within the lysosomal environment has also been determined, allowing a fuller understanding of the cellular interactions, uptake, trafficking and effects of SPIONs within a variety of cancer cells and macrophages. Overall, the behavior of SPIONS in non-phagocytotic cell lines is broadly similar to that in the specialist macrophage cells, although some differences in the uptake patterns are apparent.
Emerging novel coronavirus (2019-nCoV)—current scenario, evolutionary perspective based on genome analysis and recent developments

Abstract Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade’s first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as ‘Public Health Emergency of International Concern’ on January 30th, 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.