Miracle-dz/UniFAR-FTUs huggingface dataset:
Age influences on Propofol estimated brain concentration and entropy during maintenance and at return of consciousness during total intravenous anesthesia with target-controlled infusion in unparalyzed patients: An observational prospective trial

Purpose Aging affects pharmacodynamics/pharmacokinetics of anesthetics, but age effects on Entropy-guided total intravenous anesthesia with target-controlled infusions (TIVA-TCI) are not fully characterized. We compared aging effects on effective estimated brain concentration of Propofol (CeP) during TIVA-TCI Entropy-guided anesthesia, without neuromuscular blockade (NMB). Methods We performed an observational, prospective, single-center study enrolling 75 adult women undergoing Entropy-guided Propofol-Remifentanil TIVA-TCI for breast surgery. Primary endpoint was the relationship between age and CeP at maintenance of anesthesia (MA) during Entropy-guided anesthesia. Secondary endpoints were relationships between age and CeP at arousal reaction (AR), return of consciousness (ROC) and explicit recall evenience. We calculated a linear model to evaluate the age’s impact on observational variable and performed pairwise tests to compare old (≥65 years, n = 50) and young (<65 years, n = 25) patients or patients with and without an AR. Results We did not observe age-related differences in CeP during MA, but CeP significantly (p = 0,01) decreased with age at ROC. Entropy values during MA increased with age and were significantly higher in the elderly (RE: median 56[IQR49.3–61] vs 47.5[42–52.5],p = 0.001; SE: 51.6[45–55.5] vs 44[IQR40-50],p = 0.005). 18 patients had an AR, having higher maximum RE (92.5[78–96.3] vs 65[56.5–80.5],p<0.001), SE (79[64.8–84] vs 61[52.5–69],p = 0.03, RE-SE (12.5[9.5–16.5] vs 6 [3–9],p<0.001. Conclusion Older age was associated with lower CeP at ROC, but not during MA in unparalysed patients undergoing breast surgery. Although RE and SE during MA, at comparable CeP, were higher in the elderly, Entropy, and in particular an increasing RE-SE, is a reliable index to detect an AR.
Seasonal Variation in the Brain μ-Opioid Receptor Availability

Seasonal rhythms influence mood and sociability. The brain μ-opioid receptor (MOR) system modulates a multitude of seasonally varying socioemotional functions, but its seasonal variation remains elusive with no previously reported in vivo evidence. Here, we first conducted a cross-sectional study with previously acquired human [11C]carfentanil PET imaging data (132 male and 72 female healthy subjects) to test whether there is seasonal variation in MOR availability. Seasonal rhythms influence mood and sociability. The brain μ-opioid receptor (MOR) system modulates a multitude of seasonally varying socioemotional functions, but its seasonal variation remains elusive with no previously reported in vivo evidence. Here, we first conducted a cross-sectional study with previously acquired human [11C]carfentanil PET imaging data (132 male and 72 female healthy subjects) to test whether there is seasonal variation in MOR availability. We then investigated experimentally whether seasonal variation in daylength causally influences brain MOR availability in rats. Rats (six male and three female rats) underwent daylength cycle simulating seasonal changes; control animals (two male and one female rats) were kept under constant daylength. Animals were scanned repeatedly with [11C]carfentanil PET imaging. Seasonally varying daylength had an inverted U-shaped functional relationship with brain MOR availability in humans. Brain regions sensitive to daylength spanned the socioemotional brain circuits, where MOR availability peaked during spring. In rats, MOR availabilities in the brain neocortex, thalamus, and striatum peaked at intermediate daylength. Varying daylength also affected the weight gain and stress hormone levels. We conclude that cerebral MOR availability in humans and rats shows significant seasonal variation, which is predominately associated with seasonal photoperiodic variation. Given the intimate links between MOR signaling and socioemotional behavior, these results suggest that the MOR system might underlie seasonal variation in human mood and social behavior. SIGNIFICANCE STATEMENT Seasonal rhythms influence emotion and sociability. The central μ-opioid receptor (MOR) system modulates numerous seasonally varying socioemotional functions, but its seasonal variation remains elusive. Here we used positron emission tomography to show that MOR levels in both human and rat brains show daylength-dependent seasonal variation. The highest MOR availability was observed at intermediate daylengths. Given the intimate links between MOR signaling and socioemotional behavior, these results suggest that the MOR system might underlie seasonal variation in human mood and social behavior.
Cochlear Implant Outcomes in Neurofibromatosis Type 2: Implications for Management.

OBJECTIVE To describe our institutional experience with cochlear implantation (CI) for rehabilitation of hearing loss in Neurofibromatosis type 2 (NF2) patients. STUDY DESIGN Retrospective review between 1989 and 2019. SETTING Tertiary-care center. PATIENTS Twenty-four patients (67% female, mean age 45.6years) with NF2. Management of their ipsilateral vestibular schwannoma included microsurgery (n=12), stereotactic radiation (n=5), and observation (n=7). INTERVENTIONS Cochlear implantation. MAIN OUTCOME MEASURES Ability to obtain open-set speech, daily device usage and long-term device benefit. RESULTS All patients achieved some degree of sound awareness with CI. Nineteen patients (79%) achieved open-set speech understanding with a mean word-recognition score of 43% (range 0-88%). Patients with tumors 1.5 cm or less demonstrated the better speech understanding, without significant differences among treatment modalities. For tumors greater than 1.5 cm, patients who underwent microsurgery had a lower rate of open-set speech understanding compared to those treated with radiation or observation. Regular daily device use in 83% of patients was found. Long-term use (>10years) was observed in several patients, though some ultimately required reimplantation with an auditory brainstem implant due to progressive tumor growth. Mean follow-up duration was 4.1 years (range 0.4-15). CONCLUSIONS Cochlear implantation can be an effective treatment for hearing loss in NF2 patients provided the cochlear nerve is intact, regardless of prior management for the ipsilateral tumor. The degree of benefit varies and is influenced by tumor size. Management strategies that preserve the cochlear nerve maximize the interval during which a CI could be of benefit to NF2 patients.
Human myotube formation is determined by MyoD-Myomixer/Myomaker axis.

Myoblast fusion is essential for formations of myofibers, the basic cellular and functional units of skeletal muscles. Recent genetic studies in mice identified two long-sought membrane proteins, Myomaker and Myomixer, which cooperatively drive myoblast fusion. It is unknown whether and how human muscles, with myofibers of tremendously larger size, use this mechanism to achieve multinucleations. Here, we report an interesting fusion model of human myoblasts where Myomaker is sufficient to induce low-grade fusion, while Myomixer boosts its efficiency to generate giant myotubes. By CRISPR mutagenesis and biochemical assays, we identified MyoD as the key molecular switch of fusion that is required and sufficient to initiate Myomixer and Myomaker expression. Mechanistically, we defined the E-box motifs on promoters of Myomixer and Myomaker by which MyoD induces their expression for multinucleations of human muscle cells. Together, our study uncovered the key molecular apparatus and the transcriptional control mechanism underlying human myoblast fusion.
Adipose Tissue Inflammation and Metabolic Dysfunction in Obesity.

Several lines of preclinical and clinical research have confirmed that chronic low-grade inflammation of adipose tissue is mechanistically linked to metabolic disease and organ tissue complications in the overweight and obese organism. Despite this widely confirmed paradigm, numerous open questions and knowledge gaps remain to be investigated. This is mainly due to the intricately intertwined crosstalk of various pro- and anti- inflammatory signaling cascades involved in the immune response of expanding adipose depots, particularly the visceral adipose tissue. Adipose Tissue inflammation is initiated and sustained over time by dysfunctional adipocytes that secrete inflammatory adipokines and by infiltration of bone-marrow derived immune cells that signal via production of cytokines and chemokines. Despite its low-grade nature, adipose tissue inflammation negatively impacts remote organ function, a phenomenon that is considered causative of the complications of obesity. The aim of this review is to broadly present an overview of adipose tissue inflammation by highlighting the most recent reports in the scientific literature and summarizing our overall understanding of the field. We also discuss key endogenous antiinflammatory mediators and analyze their mechanistic role(s) in the pathogenesis and treatment of adipose tissue inflammation. In doing so, we hope to stimulate studies to uncover novel physiologic, cellular, and molecular targets for the treatment of obesity.
Disseminated ALK-positive histiocytosis with KIF5B-ALK fusion in an adult

Lianqun Qiu , Steven P. Weitzman, Loretta J. Nastoupil, Michelle D. Williams, L. Jeffrey Medeiros and Francisco Vega Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Evidence for shared genetics between physical activity, sedentary behaviour and adiposity‐related traits

Observational, cross‐sectional and longitudinal studies showed that physical activity and sedentary behaviour are associated with adiposity‐related traits, apparently in a bidirectional manner. Physical activity is also suggested to suppress the genetic risk of adiposity. Since phenotypic associations with genetic variants are not subject to reverse causation or confounding, they may be used as tools to shed light on cause and effect in this complex interdependency. We review the evidence for shared genetics of physical activity and adiposity‐related traits and for gene‐by‐physical activity interactions on adiposity‐related traits in human studies. We outline limitations, challenges and opportunities in studying and understanding of these relationships. In summary, physical activity and sedentary behaviour are genetically correlated with body mass index and fat percentage but may not be correlated with lean body mass. Mendelian randomisation analyses show that physical activity and sedentary behaviour have bidirectional relationships with adiposity. Several studies suggest that physical activity suppresses genetic risk of adiposity. No studies have yet tested whether adiposity enhances genetic predisposition to sedentariness. The complexity of the comprehensive causal model makes the assessment of the single or combined components challenging. Substantial progress in this field may need long‐term intervention studies.
Single-Cell Transcriptomics Reveals a Heterogeneous Cellular Response to BK Virus Infection

The outcome of viral infection is determined by the ability of the virus to redirect cellular systems toward progeny production countered by the ability of the cell to block these viral actions. Thus, an infected culture consists of thousands of cells, each fighting its own individual battle. ABSTRACT BK virus (BKV) is a human polyomavirus that is generally harmless but can cause devastating disease in immunosuppressed individuals. BKV infection of renal cells is a common problem for kidney transplant patients undergoing immunosuppressive therapy. In cultured primary human renal proximal tubule epithelial (RPTE) cells, BKV undergoes a productive infection. The BKV-encoded large T antigen (LT) induces cell cycle entry, resulting in the upregulation of numerous genes associated with cell proliferation. Consistently, microarray and transcriptome sequencing (RNA-seq) experiments performed on bulk infected cell populations identified several proliferation-related pathways that are upregulated by BKV. These studies revealed few genes that are downregulated. In this study, we analyzed viral and cellular transcripts in single mock- or BKV-infected cells. We found that the levels of viral mRNAs vary widely among infected cells, resulting in different levels of LT and viral capsid protein expression. Cells expressing the highest levels of viral transcripts account for approximately 20% of the culture and have a gene expression pattern that is distinct from that of cells expressing lower levels of viral mRNAs. Surprisingly, cells expressing low levels of viral mRNA do not progress with time to high expression, suggesting that the two cellular responses are determined prior to or shortly following infection. Finally, comparison of cellular gene expression patterns of cells expressing high levels of viral mRNA with those of mock-infected cells or cells expressing low levels of viral mRNA revealed previously unidentified pathways that are downregulated by BKV. Among these are pathways associated with drug metabolism and detoxification, tumor necrosis factor (TNF) signaling, energy metabolism, and translation. IMPORTANCE The outcome of viral infection is determined by the ability of the virus to redirect cellular systems toward progeny production countered by the ability of the cell to block these viral actions. Thus, an infected culture consists of thousands of cells, each fighting its own individual battle. Bulk measurements, such as PCR or RNA-seq, measure the average of these individual responses to infection. Single-cell transcriptomics provides a window to the one-on-one battle between BKV and each cell. Our studies reveal that only a minority of infected cells are overwhelmed by the virus and produce large amounts of BKV mRNAs and proteins, while the infection appears to be restricted in the remaining cells. Correlation of viral transcript levels with cellular gene expression patterns reveals pathways manipulated by BKV that may play a role in limiting infection.
Native Spanish-speaker’s test performance and the effects of Spanish-English bilingualism: results from the neuropsychological norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) project

Abstract Objective: We aimed to investigate whether or not demographically-corrected test scores derived from the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) would be less accurate if applied to Spanish-speakers with various degrees of English fluency. Spanish-English Method: One hundred and seventy primarily Spanish-speaking adults from the NP-NUMBRS project completed a comprehensive neuropsychological test battery. T-scores adjusted for age, education, and sex (but not degree of bilingualism), were derived for each test utilizing population-specific normative data. English fluency was assessed via the Controlled Oral Word Association Test in English (F-A-S), and Spanish fluency with “P-M-R,” and degree of relative English fluency was calculated as the ratio of English language words over total words produced in both languages. Effects of degree of bilingualism on the NUMBRS battery test scores (raw scores and T-scores) were examined via Pearson’s product moment correlation coefficients, and language groups (Spanish dominant vs. relative bilingual) were compared on demographically adjusted T-scores via independent samples t-tests. Results: Higher Spanish-English bilingualism was associated with higher education and SES, and was significantly associated with higher raw scores on all tests, but only associated with higher T-scores on a limited number of tests (i.e., WAIS-III Digit Symbol, Symbol Search, Letter-Number Sequencing and Trails B). Conclusion: Degree of Spanish-English bilingualism generally did not account for significant variance in the normed tests beyond the standard demographic adjustments on most tests. Overall, the normative adjustments provided by the NP-NUMBRS project appear applicable to native Spanish speakers from the U.S.-Mexico border region with various degrees of Spanish-English bilingualism.
Relationship Between Waist Circumference, Epicardial Fat Thickness, and Genders

We would like to thank Engin M. [1] for his kind interest and considerations on our article[2]. He pointed out that the waist circumference (WC) should be evaluated separately for men and women[1]. This is indeed a valid suggestion. In our study, we did not analyze WC separately for men and women, we evaluated the total population. We aimed only to assess epicardial fat thickness (EFT) and the CHA2DS2-VASC score including cardiovascular risk factors. Abdominal obesity (AO) is associated with an increased risk of cardiovascular disease. WC, which is an indicator of AO, has been shown to correlate with EFT[3]. In the study by Jeong et al., similarly to ours, no separate assessment was made between the genders[3]. In our study, it has been shown similar results. According to the Jeong et al. suggestion, when the genders were evaluated separately, it was found that both men and women were similarly correlated (r=0.218, P=004 and r=0.216, P=0.05, respectively)[3]. Our results showed that when the gender was evaluated separately, the correlation coefficient did not change much, but there could be a change in significance. This situation can be explained by using numerical variables instead of categorical variables, such as gender, while calculating the Spearman’s rank correlation coefficient and performing Pearson’s correlation analysis[4]. We therefore agree that larger-scale studies should be conducted to clarify the difference of EFT and WC between the genders. Consequently, gender-based studies in the following years may bring a more explanatory view to this situation. Fatih Aksoy1, MD https://orcid.org/0000-0002-6480-4935 1Department of Cardiology, Süleyman Demirel Faculty of Medicine, Isparta, Turkey. E-mail: dr.aksoy@hotmail.com
Human liver‐derived MAIT cells differ from blood MAIT cells in their metabolism and response to TCR‐independent activation

Mucosal associated invariant T (MAIT) cells are anti‐microbial innate‐like T cells that are abundant in blood and liver. MAIT cells express a semi‐invariant T‐cell receptor (TCR) that recognizes a pyrimidine ligand, derived from microbial riboflavin synthesis, bound to MR1. Both blood and liver derived (ld)‐MAIT cells can be robustly stimulated via TCR or by cytokines produced during bacterial or viral infection. In this study, we compared the functional and transcriptomic response of human blood and ld‐MAIT cells to TCR signals (Escherichia coli or the pyrimidine ligand) and cytokines (IL‐12 + IL‐18). While the response of blood and ld‐MAIT cells to TCR signals were comparable, following cytokine stimulation ld‐MAIT cells were more polyfunctional than blood MAIT cells. Transcriptomic analysis demonstrated different effector programmes of ld‐MAIT cells with the two modes of activation, including the enrichment of a tissue repair signature in TCR‐stimulated MAIT cells. Interestingly, we observed enhancement of IL‐12 signaling and fatty acid metabolism in untreated ld‐MAIT cells compared with blood MAIT cells. Additionally, MAIT cells from blood and liver were modulated similarly by TCR and cytokine signals. Therefore, we report that blood and ld‐MAIT cells are fundamentally different but undergo conserved changes following activation via TCR or by cytokines.
The ecology of enteroviruses in natural waters

More than 100 different enteric viruses are known to be excreted in human feces. More than 1 million viruses may be excreted per gram of feces, and concentrations as high as 500,000 infectious virus particles per liter have been detected in raw sewage. Certain enteric viruses can persist for long periods of time in the environment. Reported survival times range from 2 to 168 days in tapwater, 2 to 130 days in seawater, 25 to 125 days in soil, and up to 90 days in oysters. There are many potential routes of transmission back to man. An evaluation of the problems associated with viruses in water was prepared recently by the World Health Organization Scientific Group on Human Viruses in Water, Wastewater, and Soil which met in Geneva in October, 1978. Among its conclusions, four are pertinent to this article: (1) Viruses have been detected in the drinking water supply systems of a number of cities (including Paris and Moscow), despite the fact that those waters have received conventional water treatment cons.
Neurological outcome after minimally invasive coronary artery bypass surgery (NOMICS): An observational prospective cohort study.

BACKGROUND/OBJECTIVES Endoscopic coronary artery bypass grafting (Endo-CABG) is a minimally invasive CABG procedure with retrograde arterial perfusion. The main objective of this study is to assess neurocognitive outcome after Endo-CABG. METHODS/DESIGN In this prospective observational cohort study, patients were categorised into: Endo-CABG (n = 60), a comparative Percutaneous Coronary Intervention (PCI) group (n = 60) and a healthy volunteer group (n = 60). A clinical neurological examination was performed both pre- and postoperatively, delirium was assessed postoperatively. A battery of 6 neurocognitive tests, Quality of life (QoL) and the level of depressive feelings were measured at baseline and after 3 months. Patient Satisfaction after Endo-CABG was assessed at 3-month follow-up. Primary endpoints were incidence of postoperative cognitive dysfunction (POCD), stroke and delirium after Endo-CABG. Secondary endpoints were QOL, patient satisfaction and the incidence of depressive feelings after Endo-CABG. RESULTS In total, 1 patient after Endo-CABG (1.72%) and 1 patient after PCI (1.67%) suffered from stroke during the 3-month follow-up. POCD in a patient is defined as a Reliable Change Index ≤-1.645 or Z-score ≤-1.645 in at least two tests, and was found in respectively 5 and 6 patients 3 months after Endo-CABG and PCI. Total incidence of POCD/stroke was not different (PCI: n= 7 [15.9%]; Endo-CABG: n= 6 [13.0%], p = 0.732). ICU delirium after Endo-CABG was found in 5 (8.6%) patients. QoL increased significantly three months after Endo-CABG and was comparable with QoL level after PCI and in the control group. Patient satisfaction after Endo-CABG and PCI was comparable. At follow-up, the level of depressive feelings was decreased in all groups. CONCLUSIONS The incidence of poor neurocognitive outcome, including stroke, POCD and postoperative ICU delirium until three months after Endo-CABG is low and comparable with PCI. TRIAL REGISTRATION Registered on ClinicalTrials.gov (NCT02979782).