Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Elective Percutaneous Coronary Intervention on Global Absolute Coronary Flow and Flow Reserve Evaluated by Phase-Contrast Cine-Magnetic Resonance Imaging in Relation to Regional Invasive Physiological Indices

Background: Few studies have documented changes in global absolute coronary blood flow and global coronary flow reserve after percutaneous coronary intervention (PCI) in relation to regional physiological measures. Phase-contrast cine-magnetic resonance of the coronary sinus is a promising approach to quantify global absolute coronary blood flow. We aimed to assess the impact of elective PCI on global absolute coronary blood flow and global coronary flow reserve by quantifying coronary sinus flow (CSF) using phase-contrast cine-magnetic resonance in relation to regional physiological indices. Methods and Results: We prospectively studied 54 patients with stable angina undergoing elective PCI for a single proximal lesion. Phase-contrast cine-magnetic resonance was used to assess CSF and CSF reserve at rest and during maximum hyperemia, before and after PCI. Regional physiological indices were obtained during PCI. A complete data set was obtained in 50 patients. Hyperemic CSF increased significantly after PCI (pre-PCI, 230.2 [167.4–282.8] mL/min; post-PCI, 267.4 [224.1–346.2] mL/min; P<0.01), although 12 patients (24.0%) showed a decrease, despite successful PCI and improved fractional flow reserve. CSF reserve numerically, albeit not statistically significant (P=0.19), increased from 2.65 (1.95–3.96) to 2.98 (2.13–4.32). Patients with decreased CSF after PCI were associated with significantly greater pre-PCI hyperemic CSF, lower global coronary vascular resistance, lower regional microcirculatory resistance, and higher fractional flow reserve (all P<0.01). Conclusions: Fractional flow reserve–guided PCI in patients with single de novo lesions was associated with increased absolute hyperemic CSF, although 24% of patients showed decreased hyperemic CSF, despite successful and uncomplicated PCI. The present approach combining regional and global physiological assessments may provide a novel insight into the dynamic behavior of the coronary hemodynamics and microvascular function after PCI.
Výsledky českých žáků v šetření PISA 2015

Clanek podava zakladni informaci o celkových výsledcich ceských žaků v mezinarodnim setřeni PISA 2015 a jejich casovem vývoji. Hlavni pozornost je věnovana výsledkům v přirodnich vědach, na ktere bylo setřeni zaměřeno. Shrnuty jsou ale i výsledky v matematice a cteni. Zminěny jsou take rozdily ve výsledcich mezi různými typy skol a některa dalsi zjistěni v ramci výzkumu.
Pharmacological management of hypertension in the elderly and frail populations

ABSTRACT Introduction: Cardiovascular disease is a leading cause of mortality in the elderly. Hypertension is an important modifiable risk factor that contributes to cardiovascular morbidity and mortality. The prevalence of hypertension is known to increase with age, and hypertension has been associated with an increase in risk for cardiovascular disease in the elderly. There is a wealth of evidence that supports aggressive control of blood pressure to lower cardiovascular risk in the general population. However, there are limited data to guide management of hypertension in the elderly and frail patient subgroups. These subgroups are inadequately treated due to lack of clarity regarding blood pressure thresholds, treatment targets, comorbidities, frailty, drug interactions from polypharmacy, and high cost of care. Areas covered: We review the current evidence behind the definition, goals, and treatments for hypertension in the elderly and frail and outline a strategy that can be used to guide antihypertensive pharmacotherapy in this population. Expert commentary: Lower blood pressure to < 130/80 mm Hg in elderly patients if tolerated and promote use of combination therapy if the blood pressure is > 20/10 mm Hg over the goal blood pressure. Antihypertensive treatment regimens must be tailored to each individual based on their comorbidities, risk for adverse effects, and potential drug interactions (Figure 1).
Time-resolved neural reinstatement and pattern separation during memory decisions in human hippocampus

Significance One of the biggest computational challenges the memory system faces is to disambiguate highly similar experiences while at the same time preserving and reinstating prior memories. Remarkably, hippocampal processes have been implicated in both of these functions. However, how this is accomplished is unknown. Leveraging the spatiotemporal resolution of electrocorticography, we found evidence for memory reinstatement in both the hippocampus and occipitotemporal cortex. Interestingly, when a current experience was very similar but not identical to a prior one, occipitotemporal cortical activity still showed reinstatement of the prior memory, but hippocampal activity differentiated or disambiguated these two similar experiences. Mnemonic decision-making has long been hypothesized to rely on hippocampal dynamics that bias memory processing toward the formation of new memories or the retrieval of old ones. Successful memory encoding may be best optimized by pattern separation, whereby two highly similar experiences can be represented by underlying neural populations in an orthogonal manner. By contrast, successful memory retrieval is thought to be supported by a recovery of the same neural pattern laid down during encoding. Here we examined how hippocampal pattern completion and separation emerge over time during memory decisions. We measured electrocorticography activity in the human hippocampus and posterior occipitotemporal cortex (OTC) while participants performed continuous recognition of items that were new, repeated (old), or highly similar to a prior item (similar). During retrieval decisions of old items, both regions exhibited significant reinstatement of multivariate high-frequency activity (HFA) associated with encoding. Further, the extent of reinstatement of encoding patterns during retrieval was correlated with the strength (HFA power) of hippocampal encoding. Evidence for encoding pattern reinstatement was also seen in OTC on trials requiring fine-grained discrimination of similar items. By contrast, hippocampal activity showed evidence for pattern separation during these trials. Together, these results underscore the critical role of the hippocampus in supporting both reinstatement of overlapping information and separation of similar events.
MicroRNA‐31‐5p enhances the Warburg effect via targeting FIH

The enhanced expression of miR‐31 has been observed in many human malignancies including lung cancer, and this microRNA regulates several aspects of oncogenesis. However, the role of miR‐31‐5p in energy metabolism remains elusive. Here, we confirm that H1299 and A549 cells, 2 lung cancer cell lines, relay on aerobic glycolysis as main source of ATP. Inhibition of miR‐31‐5p leads to decreased glycolysis and ATP production, while miR‐31‐5p overexpression increases them. Hypoxia inducible factor 1 (HIF‐1) up‐regulates the expression of glycolytic enzymes, and the HIF‐1α inhibitor (FIH) inhibits HIF‐1 activity. Because FIH is a direct target of miR‐31‐5p, inhibition of miR‐31‐5p results in enhanced FIH expression and suppression of HIF‐1 signaling, while over‐expression of miR‐31‐5p has the opposite effects. Via this mechanism, miR‐31‐5p up‐regulates aerobic glycolytic genes and maintains energy homeostasis. To further validate the mechanism of miR‐31‐5p in glycolysis regulation, we show that overexpression or knockdown of FIH rescued the effects of miR‐31‐5p or miR‐31‐5p inhibitor on HIF activation and its target gene expression, respectively. Finally, by means of an A549 cell xenograft mouse model, we demonstrate that the miR‐31‐5p promotes cell proliferation via enhancing glycolysis. In summary, this study reveals that miR‐31‐5p promotes the Warburg effect via direct targeting of FIH. —Zhu, B. , Cao, X. , Zhang, W. , Pan, G. , Yi, Q. , Zhong, W. , Yan, D. MicroRNA‐31‐5p enhances the Warburg effect via targeting FIH. FASEB J. 33, 545–556 (2019). www.fasebj. org
Associations Between Early Onset of E-cigarette Use and Cigarette Smoking and Other Substance Use Among US Adolescents: A National Study

Introduction This study examines the associations between early onset of e-cigarette use and cigarette smoking and other substance use behaviors among US adolescents. Methods Data were collected via self-administered questionnaires from a nationally representative sample of 2299 US high school seniors attending public and private high schools during the spring of their senior year in 2015 as part of the Monitoring the Future study. Results A higher percentage of adolescents who began using e-cigarettes in ninth grade or earlier (early onset) were found to report current and lifetime cigarette smoking and other substance use relative to those individuals who never used e-cigarettes or those who began using e-cigarettes later in the 12th grade. Multivariate logistic regression analyses indicated that the adjusted odds of alcohol use, cigarette smoking, marijuana use, nonmedical prescription drug use, and other illicit drug use among early onset e-cigarette users were significantly greater than those for individuals never having used e-cigarettes (adjusted odds ratios [AORs] ranged 9.5-70.6, p < .001). While these associations were significant for both experimental and frequent e-cigarette users, the effects of early onset were stronger among frequent e-cigarette users. Similarly, the odds of these substance use behaviors (except alcohol) among early onset e-cigarette users were also significantly greater than the odds for later onset e-cigarette users (AORs ranged 2.8-4.1, p < .05). Conclusions Early onset of e-cigarette use was significantly associated with increased odds of cigarette smoking and other substance use behaviors. E-cigarette use is often preceded by alcohol use, cigarette smoking, and marijuana use, suggesting that more long-term prospective studies are warranted. Implications To date, no studies have examined the probability of cigarette smoking and other substance use behaviors as a function of age at onset of e-cigarette use. In the present study, early onset of e-cigarette use was significantly associated with increased odds of cigarette smoking and other substance use behaviors. The findings reinforce the importance of addressing a wide range of substances including alcohol, traditional cigarettes, and marijuana when developing early primary prevention efforts to reduce e-cigarette use among youth.
γ-Secretase promotes membrane insertion of the human papillomavirus L2 capsid protein during virus infection

Despite their importance as human pathogens, entry of human papillomaviruses (HPVs) into cells is poorly understood. The transmembrane protease &ggr;-secretase executes a crucial function during the early stages of HPV infection, but the role of &ggr;-secretase in infection and the identity of its critical substrate are unknown. Here we demonstrate that &ggr;-secretase harbors a previously uncharacterized chaperone function, promoting low pH–dependent insertion of the HPV L2 capsid protein into endosomal membranes. Upon membrane insertion, L2 recruits the cytosolic retromer, which enables the L2 viral genome complex to enter the retrograde transport pathway and traffic to the Golgi en route for infection. Although a small fraction of membrane-inserted L2 is also cleaved by &ggr;-secretase, this proteolytic event appears dispensable for HPV infection. Our findings demonstrate that &ggr;-secretase is endowed with an activity that can promote membrane insertion of L2, thereby targeting the virus to the productive infectious pathway.
Pleasure and Risk: A Qualitative Study of Sexual Behaviors Among Chinese Methamphetamine Users

In China, the number of methamphetamine (meth) users has increased dramatically in recent years. This issue has caused researchers to consider the association of meth use with public health concerns, such as the spread of sexually transmitted infections (STIs). Despite the potential outcomes of meth use, qualitative research has not as yet explored Chinese meth users’ sexual experiences and feelings associated with meth use. To contribute to the literature, this study employed semistructured interviews to collect data from 19 female and 16 male Chinese meth users (mean age = 31) who were predominantly heterosexual and were recruited from seven compulsory drug treatment institutions in Eastern China. Most participants had completed nine or fewer years of education. Gender similarities and differences were observed in the participants’ pursuits of sexual pleasure while using meth. Meth use can enhance the likelihood of high-risk sexual behaviors in both genders and therefore increases the number of public health issues. Men largely dominated the discussion of unprotected sex, while women reported transactional sex in their interviews. Based on research findings, we suggest policymakers strengthen safer-sex educational programs. Policymakers should also enhance prevention methods targeting meth use among women who may engage in transactional sex.
Assessing Variability in In-Hospital Complication Rates Between Surgical Services for Patients Undergoing Posterior Cervical Decompression and Fusion

Study Design. A retrospective study was performed including all patients who underwent posterior cervical decompression and fusion (PCDF) by an orthopedic or neurological surgeon at a single institution between January 1, 2006 and November 30, 2016, and all patients who underwent PCDF by a spine surgeon in the National Surgical Quality Improvement Project database between 2007 and 2015. In-hospital complications were compared between surgical specialties. Objective. The goal of this study was to determine if in-hospital complication rates differ significantly between surgical services for PCDF patients. Summary of Background Data. Orthopedic and neurological surgeons commonly perform PCDF, and differences in surgical opinion and management have been cited between these two specialties in recent literature. This represents a variable that should be evaluated. Methods. Cases were preliminarily identified by CPT code and confirmed using the ICD-9 code 81.03 or ICD-10 code M43.22. Cases were separated based on if the primary surgeon was an orthopedic surgeon or a neurological surgeon. The primary outcome variable was in-hospital complication rates; cohorts were compared using bivariate and multivariate analysis. Results. A total of 1221 patients at a single institution and 11,116 patients within the National Surgical Quality Improvement Project database underwent PCDF. Patients in the orthopedic surgery service had a higher proportion of bleeding requiring transfusion in both the institutional sample (14.5% vs. 9.08%, P = 0.003) and national sample (11.16% vs. 6.18%, P < 0.0001). In the national sample, orthopedic surgeons were 1.66 times as likely to encounter an in-hospital complication than neurological surgeons (95% CI: 1.44–1.91, P < 0.0001). Conclusion. When examining a large institutional sample and an even larger national sample, this study found that orthopedic surgeons were more likely to encounter perioperative bleeding requiring transfusion than neurological surgeons. When in-hospital complications were considered as a whole, in the national sample, orthopedic surgeons are more likely to encounter in-hospital complications than neurological surgeons when performing PCDF. Level of Evidence: 3
Service learning in Britain between the wars: university students and unemployed camps

This article considers the role of university staff and students in camps for the unemployed in interwar Britain. These ventures can be seen as showing continuities both with nineteenth-century social service initiatives like the educational settlements, but also with contemporary concerns with service learning. The article explores three camping movements: the camps for unemployed men organised by the Universities Council for Unemployed Camps, the Durham women’s camps organised by students from Girton College, and the camps for unemployed workers and students organised by the English nationalist Rolf Gardiner. Despite the obvious dissimilarities, the three movements showed a common concern with creating community and bridging class divisions; they were also intended to develop a new approach to leadership among the students. However, they also had unintended consequences: many student volunteers developed left-of-centre views, some shifting radically to the Left, and others committing to a lifetime of public service.
Similar Tenofovir Hair Concentrations in Men and Women after Directly-Observed Dosing of TDF/FTC: Implications for PrEP Adherence Monitoring

Objectives: Women likely require higher adherence than men to pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) for similar efficacy. Pharmacologic metrics of adherence predict efficacy better than self-report, but expected drug levels (adherence benchmarks) must be established using directly-observed therapy. We sought to Corresponding author: Catherine A. Koss, MD, Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco Box 0874, San Francisco, CA 94143-0874. catherine.koss@ucsf.edu; Tel +1 415 476 4082; Fax +1415 476 6953. Author contributions: P.L. A. , A.Y. L, J.C. -M. , and S.M. conceived and designed the parent study. C.A. K. , A.Y. L, P.B. , S.M. , M.G. , and P.L. A. designed this substudy. P.L. A. , A.Y. L. , J.C. -M. , C.M. , and S.S. contributed significantly to the acquisition of data. C.A. K. , K.K. , A.L. , H.O. , and M.G. contributed to the measurement of hair concentrations of tenofovir. C.A. K. , P.B. , M.M. , S.M. , M.G. , and P.L. A. contributed to the analysis and interpretation of data. C.A. K. , A.Y. L, S.M. , M.G. , and P.L. A. authored the manuscript, with input and important revisions from all authors, including, J.C. -M. , P.B. , C.M. , K.K. , M.M. , A.L. , S.S. , and H.O. Potential conflicts of interest: Gilead Sciences donated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as study drug, but had no other role in the design or conduct of the study or the analysis or interpretation of data. C.A. K. has received grant support paid to her institution from the Gilead Sciences Research Scholars Program in HIV. P.L. A. has received grant and contracts from Gilead Sciences, paid to his institution. A.Y. L. has led studies in which Gilead Sciences has donated study drug. HHS Public Access Author manuscript AIDS. Author manuscript; available in PMC 2020 January 12. Athor M anscript
Selective Role of RGS9-2 in Regulating Retrograde Synaptic Signaling of Indirect Pathway Medium Spiny Neurons in Dorsal Striatum

In the striatum, medium spiny neurons (MSNs) are heavily involved in controlling movement and reward. MSNs form two distinct populations expressing either dopamine receptor 1 (D1-MSN) or dopamine receptor 2 (D2-MSN), which differ in their projection targets and neurochemical composition. The activity of both types of MSNs is shaped by multiple neuromodulatory inputs processed by GPCRs that fundamentally impact their synaptic properties biasing behavioral outcomes. How these GPCR signaling cascades are regulated and what downstream targets they recruit in D1-MSN and D2-MSN populations are incompletely understood. In this study, we examined the cellular and molecular mechanisms underlying the action of RGS9–2, a key GPCR regulator in MSNs implicated in both movement control and actions of addictive drugs. Imaging cultured striatal neurons, we found that ablation of RGS9–2 significantly reduced calcium influx through NMDARs. Electrophysiological recordings in slices confirmed inhibition of NMDAR function in MSNs, resulting in enhanced AMPAR/NMDAR ratio. Accordingly, male mice lacking RGS9–2 displayed behavioral hypersensitivity to NMDAR blockade by MK-801 or ketamine. Recordings from genetically identified populations of striatal neurons revealed that these changes were selective to D2-MSNs. Surprisingly, we found that these postsynaptic effects resulted in remodeling of presynaptic inputs to D2-MSNs increasing the frequency of mEPSC and inhibiting paired-pulse ratio. Pharmacological dissection revealed that these adaptations were mediated by the NMDAR-dependent inhibition of retrograde endocannabinoid signaling from D2-MSNs to CB1 receptor on presynaptic terminals. Together, these data demonstrate a novel mechanism for pathway selective regulation of synaptic plasticity in MSNs controlled by GPCR signaling. SIGNIFICANCE STATEMENT This study identifies a role for a major G-protein regulator in controlling synaptic properties of striatal neurons in a pathway selective fashion.
Biomarker P16 predicts progression risk of anal low-grade squamous intraepithelial lesions

Objectives: The aim of this study was to determine whether biomarker P16INK4a predicts progression risk for anal low-grade squamous intraepithelial lesions (LSILs). Design: A retrospective study. Methods: One hundred and nine HIV-infected and 18 HIV-uninfected patients with biopsy-proven anal LSIL at initial screening underwent surveillance high-resolution anoscopy and biopsy within 2 years of diagnosis. P16 immunohistochemistry was performed on index lesions and evaluated using a semi-quantitative scoring system. The association of predictors and lesional outcomes (progression, persistence or regression) was analysed using ordinal logistic regression models. A subset of p16-positive LSILs was tested for high-risk human papillomavirus (HR-HPV) DNA using real-time PCR. Results: Upon follow-up, 46 (36%) LSILs progressed to high-grade squamous intraepithelial lesion (HSIL), 50 (40%) persisted as LSIL and 31 (24%) regressed to benign mucosa (median 16 months, range 5–24 months). Age, sex, race, history of condylomata, CD4+ T-cell count and HIV plasma viral load were similar regardless of clinical outcome. P16 immunoreactivity of index lesion was classified as block-positive (n = 36), focal-positive (n = 49) or negative (n = 42). Sixty-four percent of block-positive lesions progressed, as opposed to 35% of focal-positive and 14% of negative lesions (P < 0.001). HR-HPV DNA was detected in 90% of p16 block-positive lesions vs. 55% of focal-positive lesions. In unadjusted analyses, positive p16, HIV and former smoker status were significantly associated with lesional persistence and progression. P16 remained the only significant predictor in an adjusted model. Conclusion: Biomarker p16 is the strongest predictor for anal LSIL-to-HSIL progression, outperforming other risk factors. To enhance the overall effectiveness of surveillance, we propose using p16 immunohistochemistry to help stratify patients at high vs. low risk of progression.