Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term effect of yogic practices on diurnal metabolic rates of healthy subjects

Background : The metabolic rate is an indicator of autonomic activity. Reduced sympathetic arousal probably resulting in hypometabolic states has been reported in several yogic studies. Aim : The main objective of this study was to assess the effect of yoga training on diurnal metabolic rates in yoga practitioners at two different times of the day (at 6 a.m. and 9 p.m.). Materials and Methods : Eighty eight healthy volunteers were selected and their metabolic rates assessed at 6 a.m. and 9 p.m. using an indirect calorimeter at a yoga school in Bangalore, India. Results and conclusions: The results show that the average metabolic rate of the yoga group was 12% lower than that of the non-yoga group ( P < 0.001) measured at 9 p.m. and 16% lower at 6 a.m. ( P < 0.001). The 9 p.m. metabolic rates of the yoga group were almost equal to their predicted basal metabolic rates (BMRs) whereas the metabolic rate was signiﬁ cantly higher than the predicted BMR for the non-yoga group. The 6 a.m. metabolic rate was comparable to their predicted BMR in the non-yoga group whereas it was much lower in the yoga group ( P < 0.001). The lower metabolic rates in the yoga group at 6 a.m. and 9 p.m. may be due to coping strategies for day-to-day stress, decreased sympathetic nervous system activity and probably, a stable autonomic nervous system response (to different stressors) achieved due to training in yoga. ABSTRACT An understanding of metabolism at different times of the day has significant implications due to its link to sleep, health, stress and fatigue, ultimately determining the quality of life. BMR is the lowest (basal) metabolic rate measured just after waking from a night(cid:146)s sleep. [1] It is well known that sleep is a restorative process wherein the body synthesizes its necessary chemicals for growth, maintenance and development. Rejuvenation and repair take place during sleep. [2] Sleep generally brings down the metabolic rate by about 10%. [1,3] Low basal metabolic rates of yoga practitioners have been reported. [4] Hypometabolic states have been reported in yogic studies [5-8] wherein short and immediate effects of meditation and relaxation were observed.
An Oncolytic Adenovirus Targeting Transforming Growth Factor b Inhibits Protumorigenic Signals and Produces Immune Activation: A Novel Approach to Enhance Anti-PD-1 and Anti-CTLA-4 Therapy

In an effort to develop a new therapy for cancer and to improve antiprogrammed death inhibitor-1 (anti-PD-1) and anticytotoxic T lymphocyte-associated protein (anti-CTLA-4) responses, we have created a telomerase reverse transcriptase promoter-regulated oncolytic adenovirus rAd.sT containing a soluble transforming growth factor receptor II fused with human IgG Fc fragment (sTGF b RIIFc) gene. Infection of breast and renal tumor cells with rAd.sT produced sTGF b RIIFc protein with dose-dependent cytotoxicity. In immunocompetent mouse 4T1 breast tumor model, intratumoral delivery of rAd.sT inhibited both tumor growth and lung metastases. rAd.sT downregulated the expression of several transforming growth factor b (TGF b ) target genes involved in tumor growth and metastases, inhibited Th2 cytokine expression, and induced Th1 cytokines and chemokines, and granzyme B and perforin expression. rAd.sT treatment also increased the percentage of CD8 + T lymphocytes, promoted the generation of CD4 + T memory cells, reduced regulatory T lymphocytes (Tregs), and reduced bone marrow-derived suppressor cells. Importantly, rAd.sT treatment increased the percentage of CD4 + T lymphocytes, and promoted differentiation and maturation of antigen-presenting dendritic cells in the spleen. In the immunocompetent mouse Renca renal tumor model, similar therapeutic effects and immune activation results were observed. In the 4T1 mammary tumor model, rAd.sT improved the inhibition of tumor growth and lung and liver metastases by anti-PD-1 and anti-CTLA-4 antibodies. Analysis of the human breast and kidney tumors showed that a signiﬁcant number of tumor tissues expressed high levels of TGF b and TGF b -inducible genes. Therefore, rAd.sT could be a potential enhancer of anti-PD-1 and anti-CTLA-4 therapy for treating breast and kidney cancers.
EFFECTS OF NEUROPEPTIDE Y (NPY) AND ETHANOL ON AROUSAL AND ANXIETY-LIKE BEHAVIOR IN ALCOHOL-PREFERRING (P) RATS

Neuropeptide Y is abundant in the mammalian brain and plays a prominent role in behaviors related to negative affect and alcohol. NPY suppresses anxiety-like behavior and alcohol-drinking behaviors in a wide array of rodent models, and also affects changes in these behaviors produced by fearful and stressful stimuli. Rats selectively bred for high alcohol preference (P rats) appear to be particularly sensitive to the behavioral effects of NPY. The dual purpose of the present investigation was to determine the effects of intraventricular NPY on [1] the acoustic startle reflex (ASR) of P rats in a high-anxiety setting and [2] social interaction behavior of P rats. In Experiment 1, P rats were either cycled through periods of long-term ethanol access and abstinence or they remained ethanol-naïve. Rats were injected with one of four NPY doses and tested for ASR before and after footshock stress. NPY suppressed ASR in all P rats regardless of shock condition or drinking history. In Experiment 2, rats received intraventricular infusion of one of four NPY doses and then were injected with either ethanol (0.75 g/kg) or saline and tested for social interaction. NPY increased social interaction in P rats even at doses that suppressed locomotor activity, regardless of ethanol dose. Suppression of anxiety-like and arousal behaviors by NPY in the present study confirm a role for NPY in alcohol-related behaviors in alcohol-preferring P rats. clear effect of acute stress exposure on the acoustic startle response in P rats in this study. Past studies have shown that the effects of acute stressors on particular behaviors may be augmented during alcohol abstinence. Rats exposed to mild restraint stress 3 days into abstinence exhibit decreases in social interaction (i.e. increased anxiety) relative to
Wnt / b -catenin signaling is a key downstream mediator of MET signaling in glioblastoma stem cells

of pathways analysis, we identiﬁed signaling pathways that are enriched in MET high / + populations, one of which is Wnt / b -catenin signaling pathway. To determine molecular interaction and the biological consequences of MET and Wnt / b -catenin signaling, we used pharmacological and shRNA-mediated genetic inhibition and performed various molecular and cellular analyses, including ﬂow cytometry, immunohistochemistry, and clonogenicity assays. Results. We found that Wnt / b -catenin signaling is highly active in MET high / + cells, compared with bulk tumor cells. We also showed that Wnt / b -catenin signaling activities in GBM are directly modulated by the addition of ligand-mediated MET activation or MET inhibition. Furthermore, the ectopic expression of active- b -catenin (S37A and S45Y) rescued the phenotypic effects caused by MET inhibition. Conclusion. These data suggest that Wnt / b -catenin signaling is a key downstream effector of MET signaling and contributes to the maintenance of GSC and GBM malignancy.
Similar Frequency and Inducibility of Intact Human Immunodeficiency Virus-1 Proviruses in Blood and Lymph Nodes

Background. The human immunodeficiency virus (HIV)-1 latent reservoir (LR) in resting CD4 + T cells is a barrier to cure. LR measurements are commonly performed on blood samples and therefore may miss latently infected cells residing in tissues, in-cluding lymph nodes. Methods. We determined the frequency of intact HIV-1 proviruses and proviral inducibility in matched peripheral blood (PB) and lymph node (LN) samples from 10 HIV-1-infected patients on antiretroviral therapy (ART) using the intact proviral DNA assay and a novel quantitative viral induction assay. Prominent viral sequences from induced viral RNA were characterized using a next-generation sequencing assay. Results. The frequencies of CD4 + T cells with intact proviruses were not significantly different in PB versus LN (61/10 6 vs 104/10 6 CD4 + cells), and they were substantially lower than frequencies of CD4 + T cells with defective proviruses. The frequencies of CD4 + T cells induced to produce high levels of viral RNA were not significantly different in PB versus LN (4.3/10 6 vs 7.9/10 6 ), but they were 14-fold lower than the frequencies of cells with intact proviruses. Sequencing of HIV-1 RNA from induced proviruses re-vealed comparable sequences in paired PB and LN samples. Conclusions. These results further support the use of PB as an appropriate proxy for the HIV-1 LR in secondary lymphoid organs.
Lipid droplet assembly factor-1 and seipin form a lipid droplet assembly complex

Lipid droplets (LDs) originate from the endoplasmic reticulum (ER) to store triacylglycerol (TG) and cholesterol esters. The ER protein seipin was shown to localize to ER-LD contacts soon after LDs form, but what determines the sites of initial LD biogenesis in the ER is unknown. Here we identify TMEM159, now re-named lipid droplet-assembly factor 1 (LDAF1), as an interaction partner of seipin. Together, LDAF1 and seipin form a ~600kDa oligomeric complex that copurifies with TG. LDs form at LDAF1-seipin complexes, and re-localization of LDAF1 to the plasma membrane co-recruits seipin and redirects LD formation to these sites. Once LDs form, LDAF1 dissociates from seipin and moves to the LD surface. In the absence of LDAF1, LDs form only at significantly higher cellular TG concentrations. Our data suggest that the LDAF1-seipin complex is the core protein machinery that facilitates LD biogenesis and determines the sites of their formation in the ER. eTOC Blurb: Chung et al. identify and characterize an oligomeric LDAF1-seipin protein complex in the endoplasmic reticulum that determines the sites of lipid droplet formation. This complex appears to promote phase separation of triglyceride neutral lipids within the complex, thus defining the sites of lipid droplet formation.
Memantine effects on EEG measures of putative excitatory/ inhibitory balance in schizophrenia

BACKGROUND— Abnormalities in cortical excitation and inhibition (E/I) balance are thought to underlie sensory and information processing deficits in schizophrenia (SZ). Deficits in early auditory information processing (EAIP) mediate both neurocognitive and functional impairment, and appear to be normalized by acute treatment with the NMDA antagonist, memantine (MEM). METHODS— Thirty-six subjects with a diagnosis of schizophrenia and 31 control subjects (NCS) underwent EEG recordings. Subjects ingested either placebo or MEM (10 or 20 mg) in a double-blind, within-subject cross-over randomized design. The aperiodic, 1/f-like scaling property of the neural power spectra, which is thought to index relative E/I balance, was estimated using a robust linear regression algorithm. RESULTS— SZ patients had greater aperiodic components compared to NCS (p<.01, d=.64), which was normalized after 20 mg MEM. Analysis revealed a significant dose x diagnosis interaction (p<.0001, d=.82). Further, the “MEM effect” (change in aperiodic component in MEM vs. placebo conditions) was associated with baseline attention and vigilance (r=.54, p<.05) and MEM-induced enhancements in gamma power (r=−.60, p<.01). CONCLUSIONS— Findings confirmed E/I balance abnormalities in SZ that were normalized with acute MEM administration and suggest that neurocognitive profiles may predict treatment response based on E/I sensitivity. These data provide “proof-of-concept” evidence for the utility of E/I balance indices as metrics of acute pharmacologic sensitivity for central nervous system therapeutics.
Regional Variations of HR-pQCT Morphological and Biomechanical Measurements of Bone Segments and Their Associations With Whole Distal Radius and Tibia Mechanical Properties

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a promis-ing imaging modality that provides an in vivo three-dimensional (3D) assessment of bone microstructure by scanning ﬁxed regions of the distal radius and tibia. However, how microstructural parameters and mechanical analysis based on these segment scans cor- relate to whole distal radius and tibia mechanics are not well-characterized. On 26 sets of cadaveric radius and tibia, HR-pQCT scans were performed on the standard scan segment, a segment distal to the standard segment, and a segment proximal to the standard segment. Whole distal radius and tibia stiffness were determined through mechanical testing. Segment bone stiffness was estimated using linear ﬁnite element (FE) analysis based on segment scans. Standard morphological and individual trabecula segmentation (ITS) analyses were used to estimate microstructural properties. Signiﬁcant variations in microstructural parameters were observed among segments at both sites. Correlation to whole distal radius and tibia stiffness was moderate for microstructural parameters at the standard segment, but correlation was signiﬁcantly increased for FE-predicted segment bone stiffness based on standard segment scans. Similar correlation strengths were found between FE-predicted segment bone stiffness and whole distal radius and tibia stiffness. Additionally, microstructural parameters at the distal segment had higher cor- relation to whole distal radius and tibia stiffness than at standard or proximal segments. Our results suggest that FE-predicted segment stiffness is a better predictor of whole distal radius and tibia stiffness for clinical HR-pQCT analysis and that microstructural parameters at the distal segment are more highly correlated with whole distal radius and tibia stiffness than at the standard or proximal segments. [DOI: 10.1115/1.4044175]
LETTER TO THE EDITOR Rs2293871 regulates HTRA1 expression and affects cerebral small vessel stroke and Alzheimer’s disease

Cerebral small vessel disease (CSVD) is involved in many kinds of pathological processes, and associated with increased risk of stroke, dementia and death (Mishra et al., 2019). To date, genome-wide association studies (GWAS) have identified several white matter hyperintensity (WMH) loci, which could only explain a small proportion of the heritable component (Fornage et al., 2011; Verhaaren et al., 2015; Traylor et al., 2016, 2019; Elliott et al., 2018). In a recent study, Mishra and colleagues presented a composite extreme phenotype design using distribution of WMH and brain infarcts to detect genetic variants associated with Mendelian forms of CSVD (Mishra et al., 2019). Interestingly, Mishra et al. identified a common intronic variant rs2293871 in HTRA1 using a single variant association test (P = 4.72 10 ). They also found that rs2293871 was associated with SVD-related phenotypes including small vessel ischaemic stroke (P = 6.14 10 ) and WMH (P = 0.03). In addition, Mishra and colleagues conducted an expression quantitative trait loci (eQTL) analysis, and identified that rs2293871 could regulate the expression of HTRA1 in blood. In brief, they provided important findings about the genetic variants underlying CSVD. In their study, Mishra et al. evaluated the association of extreme CSVD risk variant rs2293871 with small vessel ischaemic stroke and WMH. It is still unclear whether rs2293871 is associated with other CSVD-related phenotypes such as intracerebral haemorrhage (ICH) and dementia. To date, demonstrating the association of rs2293871 with CSVD-related phenotypes may contribute to understanding the shared mechanisms between CSVD and other related phenotypes. In addition, our recent studies have clearly shown that the genetic variant could regulate the gene expression with tissue, cell or disease status specificity (Hu et al., 2017; Liu et al., 2017a, 2018a, b, 2019). However, Mishra and colleagues only evaluated the association of rs2293871 variant with HTRA1 expression in blood. It remains unclear whether rs2293871 could regulate the expression of HTRA1 in human brain tissues. Hence, both of these concerns prompted us to evaluate their findings further. First, we evaluated and validated the association of rs2293871 with CSVD-related phenotypes including small vessel ischaemic stroke, ICH (deep ICH and lobar ICH), doi:10.1093/brain/awz305 BRAIN 2019: 142; 1–5 | e61
Circulating BRAF V600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma

Background: BRAF V600E is the most common mutation in papillary thyroid carcinoma (PTC) and can be associated with aggressive disease. Previously, a highly sensitive blood RNA-based BRAF V600E assay was reported. The objective of this study was to assess the correlation of BRAF V600E circulating tumor RNA levels with surgical and medical treatment. Methods: Circulating BRAF V600E levels were assessed in (i) a murine model of undifferentiated (anaplastic) thyroid carcinoma with known BRAF V600E mutation undergoing BRAF V600E -inhibitor ( BRAFi ) treatment, and (ii) in 111 patients enrolled prior to thyroidectomy ( n = 86) or treatment of advanced recurrent or metastatic PTC ( n = 25). Blood samples were drawn for BRAF V600E analysis before and after treatment. Testing characteristics were assessed and positivity criteria optimized. Changes in blood BRAF V600E values were assessed and compared to clinical characteristics and response to therapy. Results: In a murine model of anaplastic thyroid carcinoma with BRAF V600E mutation, blood BRAF V600E RNA correlated with tumor volume in animals treated with BRAFi . In tissue BRAF V600E -positive ( n = 36) patients undergoing initial surgery for PTC, blood BRAF V600E levels declined postoperatively (median 370.0–178.5 fg/ng; p = 0.002). In four patients with metastatic or poorly differentiated thyroid carcinoma receiving targeted therapies, blood BRAF V600E declined following therapy and corresponded with radiographic evidence of partial response or stable disease. Conclusions: This study shows the correlation of blood BRAF V600E levels in response to treatment in both an established animal model of thyroid cancer and in patients with BRAF V600E -positive tumors with all stages of disease. This assay represents an alternative biomarker in patients with positive thyroglobulin antibodies, and tumors, which do not express thyroglobulin.
Is Socioeconomic Incorporation Associated with a Healthier Diet? Dietary Patterns among Mexican-American Children

With each successive generation in the United States, Mexican-origin families lose their initial dietary advantages. Focusing on children’s diets, we ask whether greater socioeconomic status (SES) can help buffer Mexican-origin children in immigrant families from negative dietary acculturation or whether it exacerbates these dietary risks. Pooling data from the 1999 to 2009 waves of the continuous National Health and Nutrition Examination Survey, we test whether the association between generational status and Mexican-origin children’s nutrition varies by the family’s SES. When predicting children’s overall dietary quality using the Healthy Eating Index (2010) and predicting unhealthy dietary patterns, we find stronger evidence of segmented assimilation, whereby greater family average SES is associated with better diets across generations of Mexican-origin children. High-status Mexican-origin parents appear able to buffer their children against generational dietary declines documented in the acculturation literature.
Prevalence and correlates of eating disorder co-morbidity in patients with bipolar disorder 1

This study was designed to document eating disorder symptoms in a well-defined sample of patients with bipolar disorder and to evaluate the relationship of current loss of control over eating (LOC) to demographic and clinical features hypothesized to characterize bipolar patients at risk for disordered eating. Eighty-one patients enrolled in the Bipolar Disorder Center for Pennsylvanians provided demographic information and completed the Structured Clinical Interview for DSM-IV Axis I Disorders. The Eating Disorder Examination was administered by independent clinicians to evaluate current and lifetime eating disorder symptomatology. Twenty-one percent of participants met DSM-IV criteria for a lifetime eating disorder, and 44% reported a history of LOC. Patients who endorsed weekly LOC during the past six months ( n = 18) were heavier, had more atypical depressive symptoms, and were more likely to have a lifetime substance use disorder compared to patients in the rest of the sample ( n = 63). These findings indicate that eating disorder symptoms are prevalent in patients with bipolar disorder and are associated with obesity and other psychiatric morbidity. Screening for eating disorders in bipolar patients is warranted, as intervention may minimize distress and improve treatment outcome.
MyD88 Costimulation in Donor CD8+ T Cells Enhances the Graft-versus-Tumor Effect in Murine Hematopoietic Cell Transplantation

Key Points MyD88 costimulation in donor CD8+ T cells improves the graft-versus-tumor effect. MyD88-costimulated CD8+ T cells are more activated with improved cytotoxic function. Donor-derived lymphocytes from allogeneic hematopoietic cell transplantation (allo-HCT) or donor lymphocyte infusion can mediate eradication of host tumor cells in a process labeled the graft-versus-tumor (GVT) effect. Unfortunately, these treatments have produced limited results in various types of leukemia because of an insufficient GVT effect. In this context, molecular engineering of donor lymphocytes to increase the GVT effect may benefit cancer patients. Activating MyD88 signaling in CD8+ T cells via TLR enhances T cell activation and cytotoxicity. However, systemic administration of TLR ligands to stimulate MyD88 could induce hyperinflammation or elicit protumor effects. To circumvent this problem, we devised a synthetic molecule consisting of MyD88 linked to the ectopic domain of CD8a (CD8α:MyD88). We used this construct to test the hypothesis that MyD88 costimulation in donor CD8+ T cells increases tumor control following allo-HCT in mice by increasing T cell activation, function, and direct tumor cytotoxicity. Indeed, an increase in both in vitro and in vivo tumor control was observed with CD8α:MyD88 T cells. This increase in the GVT response was associated with increased T cell expansion, increased functional capacity, and an increase in direct cytotoxic killing of the tumor cells. However, MyD88 costimulation in donor CD8+ T cells was linked to increased yet nonlethal graft-versus-host disease in mice treated with these engineered CD8+ T cells. Given these observations, synthetic CD8α:MyD88 donor T cells may represent a unique and versatile approach to enhance the GVT response that merits further refinement to improve the effectiveness of allo-HCT.