Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA Repair in Despair—Vitamin D Is Not Fair

The role of vitamin D as a treatment option for neoplastic diseases, once considered to have a bright future, remains controversial. The preclinical studies discussed herein show compelling evidence that Vitamin D Derivatives (VDDs) can convert some cancer and leukemia cells to a benign phenotype, by differentiation/maturation, cell cycle arrest, or induction of apoptosis. Furthermore, there is considerable, though still evolving, knowledge of the molecular mechanisms underlying these changes. However, the attempts to clearly document that the treatment outcomes of human neoplastic diseases can be positively influenced by VDDs have been, so far, disappointing. The clinical trials to date of VDDs, alone or combined with other agents, have not shown consistent results. It is our contention, shared by others, that there were limitations in the design or execution of these trials which have not yet been fully addressed. Based on the connection between upregulation of JNK by VDDs and DNA repair, we propose a new avenue of attack on cancer cells by increasing the toxicity of the current, only partially effective, cancer chemotherapeutic drugs by combining them with VDDs. This can impair DNA repair and thus kill the malignant cells, warranting a comprehensive study of this novel concept. J. Cell. Biochem. 117: 1733–1744, 2016. © 2016 Wiley Periodicals, Inc.
Metabolic Fate of Branched‐Chain Amino Acids During Adipogenesis, in Adipocytes From Obese Mice and C2C12 Myotubes

Branched‐chain amino acid (BCAA) catabolism is regulated by the branched‐chain aminotransferase (BCAT2) and the branched‐chain α‐keto acid dehydrogenase complex (BCKDH). BCAT2 and BCKDH expression and activity are modified during adipogenesis and altered in adipose tissues of mice with genetic or diet‐induced obesity. However, little is known about how these modifications and alterations affect the intracellular metabolic fate of BCAAs during adipogenesis, in adipocytes from mice fed a control or high‐fat diet or in C2C12 myotubes. Here, we demonstrate that BCAAs are mainly incorporated into proteins during the early stages of adipocyte differentiation. However, they are oxidized and incorporated into lipids during the late days of differentiation. Conversely, 92% and 97% of BCAA were oxidized, 1.6% and 6% were used for protein synthesis and 1.2% and 1.5% were incorporated into lipids in adipocytes from epididymal and subcutaneous adipose tissue, respectively. All three pathways were decreased in adipocytes from mice fed a high‐fat diet. In C2C12 myotubes, leucine is mainly used for protein synthesis and palmitate is incorporated into lipids. Interestingly, leucine decreased both palmitate oxidation and its incorporation to lipids and proteins; and palmitate increased leucine oxidation and decreased its incorporation to lipids and proteins in a dose‐dependent manner. These results demonstrate that BCAA metabolic fate differs between the early and late stages of adipocyte differentiation and in adipocytes from mice fed a control or high‐fat diet; and that leucine affects the metabolic fate of palmitate and vice versa in C2C12 myotubes. J. Cell. Biochem. 118: 808–818, 2017. © 2016 Wiley Periodicals, Inc.
Noninvasive diagnosis of deep venous thrombosis.

Eighty-five patients suspected of having lower-extremity deep venous thrombosis (DVT) participated in a prospective study to test the diagnostic accuracy of four noninvasive techniques: Doppler ultrasonic flow study, electrical impedance plethysmography, the serial dilution protamine sulfate test, and an extensive physical examination. Ascending radiocontrast phlebography was the diagnostic standard of reference. We found that (1) when both Doppler and impedance examinations were positive, the diagnosis of DVT could be considered virtually certain; (2) impedance and Doppler examinations, when used in combination, were reliable screening tests capable of establishing or excluding the presence of thigh DVT; (3) physical examination and the serial dilution protamine sulfate test were unreliable screening techniques for DVT; (4) techniques other than the noninvasive methods investigated were needed to reliably detect or to exclude popliteal and calf DVT. (Arch Intern Med136:1091-1096, 1976)
Separase: Function Beyond Cohesion Cleavage and an Emerging Oncogene

Proper and timely segregation of genetic endowment is necessary for survival and perpetuation of every species. Mis‐segregation of chromosomes and resulting aneuploidy leads to genetic instability, which can jeopardize the survival of an individual or population as a whole. Abnormality with segregation of genetic contents has been associated with several medical consequences including cancer, sterility, mental retardation, spontaneous abortion, miscarriages, and other birth related defects. Separase, by irreversible cleavage of cohesin complex subunit, paves the way for metaphase/anaphase transition during the cell cycle. Both over or reduced expression and altered level of separase have been associated with several medical consequences including cancer, as a result separase now emerges as an important oncogene and potential molecular target for medical intervenes. Recently, separase is also found to be essential in separation and duplication of centrioles. Here, I review the role of separase in mitosis, meiosis, non‐canonical roles of separase, separase regulation, as a regulator of centriole disengagement, nonproteolytic roles, diverse substrates, structural insights, and association of separase with cancer. At the ends, I proposed a model which showed that separase is active throughout the cell cycle and there is a mere increase in separase activity during metaphase contrary to the common believes that separase is inactive throughout cell cycle except for metaphase. J. Cell. Biochem. 118: 1283–1299, 2017. © 2016 Wiley Periodicals, Inc.
CD3+CD8+NKG2D+ T Lymphocytes Induce Apoptosis and Necroptosis in HLA‐Negative Cells via FasL–Fas Interaction

An important problem in cellular immunology is to identify new populations of cytotoxic lymphocytes capable of killing tumor cells that have lost classical components of MHC‐machinery and to understand mechanisms of the death of these cells. We have previously found that CD4+CD25+ lymphocytes appear in the lymphokine‐activated killer (LAK) cell culture, which carry Tag7 (PGRP‐S) and FasL proteins on their surface and can kill Hsp70‐ and Fas‐expressing HLA‐negative cells. In this work, we have continued to study the mechanisms of killing of the HLA‐negative tumor cells, focusing this time on the CD8+ lymphocytes. We show that after a tumor antigen contact the IL‐2 activated CD8+ lymphocytes acquire ability to lyse tumor cells bearing this antigen. However, activation of the CD8+ lymphocytes in the absence of antigen causes appearance of a cytotoxic population of CD8+NKG2D+ lymphocytes, which are able to lyse HLA‐negative cancer cells that have lost the classic mechanism of antigen presentation. These cells recognize the noncanonical MicA antigen on the surface of HLA‐negative K562 cells but kill them via the FasL–Fas interaction, as do cytotoxic T lymphocytes. FasL presented on the lymphocyte surface can trigger both apoptosis and necroptosis. Unlike in the case of TNFR1, another cell death receptor, no switching to alternative processes has been observed upon induction of Fas‐dependent cell death. It may well be that the apoptotic and necroptotic signals are transduced separately in the latter case, with the ability of FasL+ lymphocytes to induce necroptosis allowing them to kill tumor cells that escape apoptosis. J. Cell. Biochem. 118: 3359–3366, 2017. © 2017 Wiley Periodicals, Inc.
First description of a double‐wall balloon breach during cryoballoon ablation for atrial fibrillation

To date, this is the first published report of a double‐wall breach while using the cryoballoon ablation catheter during the treatment of a patient with atrial fibrillation; however, there have been previous balloon breaches in both the second and third‐generation cryoballoon ablation catheter usage. In this report, we describe the case of a double‐wall balloon breach and the intraoperative care that was necessary to stabilize the patient. Additionally, we review other known cases of double‐wall balloon breaches, and we examine the safety systems of the cryoballoon catheter that mitigate some of the potential patient complications.
Sudden cardiac death in nonischemic cardiomyopathy: Refining risk assessment

Sudden cardiac death (SCD) risk assessment among patients with nonischemic cardiomyopathy (NICM) has been has been less straightforward than for patients with ischemic cardiomyopathy. The common surrogate that has been associated with highest SCD risk for all cardiomyopathies, and which has been universally used to guide implantation of primary‐prevention implantable cardioverter‐defibrillators (ICDs), is left ventricular ejection fraction (LVEF) ≤35%. However, this practice has been called into question, especially in light of recent trials suggesting that ICD treatment may not be of additional survival benefit among those with NICM treated with optimal medical therapy. This Clinical Review attempts to offer refinements to the current practice of SCD risk assessment among patients with NICM, with specific focus on importance of NICM etiology and efforts to identify myocardial scarring and arrhythmogenic substrate, both of which may provide greater information about SCD risk than the LVEF alone. These concepts are illustrated further as they apply to hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and cardiac sarcoidosis, all of which are increasingly recognized NICM substrates associated with SCD and for which refinements for assessing risk are lacking in conventional guidelines.
Exercise stress test reveals ineligibility for subcutaneous implantable cardioverter defibrillator in patients with Brugada syndrome

The eligibility of patients with Brugada syndrome (BrS) for implantation of a subcutaneous implantable cardioverter defibrillator (S‐ICD) is not well known. This study aimed to clarify the eligibility of BrS patients for S‐ICD using electrocardiography (ECG) at rest and during exercise testing. We also analyzed factors associated with ineligibility for S‐ICD from standard 12‐lead ECG at rest.
A Randomized Clinical Trial of the Effect of an Angina Self-Management Intervention on Health Outcomes of Patients With Coronary Heart Disease

Purpose The aim of this study was to test the effect of a psychoeducational intervention to enhance angina pectoris (AP) symptom self-management. Design A two-group, single-blind, randomized controlled trial. Methods Following institutional review board approval, a convenience sample of cardiac inpatients was recruited. Within 2 weeks following discharge, the Angina Self-Management (ASM) intervention group (n = 39) received a nurse-delivered, telephone intervention focused on AP symptom monitoring and management. The control group (n = 41) received an attention-control telephone call. Physical function, anxiety, and angina frequency were assessed between 3 and 6 months postintervention. Findings Men in the ASM group (n = 24) reported better physical function and lower anxiety than men in the control group (n = 26). Women in the ASM group (n = 15) reported worse physical function and higher anxiety than women (n = 15) in the control group. Conclusions Angina symptom monitoring may be more difficult for women. Rehabilitation nurses should be proactive in addressing issues associated with women’s AP symptom management.
Commentary: Rantosomes and Ravosomes

AbstractThose who cannot remember the past are condemned to repeat it. —George SantayanaI am fortunate to have entered the liposome research field in its infancy. In that “golden age” of liposome research, scientific advances related to lipid vesicles appeared in the literature on a regular basis and there was little danger of repeating a study because there was so little published. Many of the potential uses of liposomes in drug delivery that have come to be, were discussed in two creative and prescient articles published in 1976 in the New England Journal of Medicine by Gregory Gregoriadis (1). At liposome/ drug carrier meetings, discussions raged over materials, mechanisms, models, methods and structures. My colleagues and I published a few papers dealing with liposome preparation and extrusion through polycarbonate membranes to form defined diameter populations of liposomes (2-4). The extrusion method is widely used and like the original Bangham method (5) for making MLV, it has become so a part of mak.
Advanced 2-Dimensional Quantitative Coronary Angiographic Analysis for Prediction of Fractional Flow Reserve in Intermediate Coronary Stenoses

Purpose: The widespread clinical application of coronary computed tomography angiography (CCTA) has resulted in increased referral patterns of patients with intermediate coronary stenoses to invasive coronary angiography. We evaluated the application of advanced quantitative coronary angiography (A-QCA) for predicting fractional flow reserve (FFR) in intermediate coronary lesions detected on CCTA. Materials and Methods: Fifty-six patients with 66 single intermediate coronary lesions (≥50% to 80% stenosis) on CCTA prospectively underwent coronary angiography and FFR. A-QCA including calculation of the Poiseuille-based index defined as the ratio of lesion length to the fourth power of the minimal lumen diameter (MLD) was performed. Significant stenosis was defined as FFR ⩽0.80. Results: The mean FFR was 0.86±0.09, and 18 lesions (27%) were functionally significant. FFR correlated with lesion length (R=−0.303, P=0.013), MLD (R=0.527, P<0.001), diameter stenosis (R=−0.404, P=0.001), minimum lumen area (MLA) (R=0.530, P<0.001), lumen stenosis (R=−0.400, P=0.001), and Poiseuille-based index (R=−0.602, P<0.001). The optimal cutoff values for MLD, MLA, diameter stenosis, and lumen stenosis were ⩽1.3 mm, ⩽1.5 mm2, >44%, and >69%, respectively (maximum negative predictive value of 94% for MLA, maximum positive predictive value of 58% for diameter stenosis). The Poiseuille-based index was the most accurate (C statistic 0.86, sensitivity 100%, specificity 71%, positive predictive value 56%, and negative predictive value 100%) predictor of FFR ⩽0.80, but showed the lowest interobserver agreement (intraclass correlation coefficient 0.37). Conclusions: A-QCA might be used to rule out significant ischemia in intermediate stenoses detected by CCTA. The diagnostic application of the Poiseuille-based angiographic index is precluded by its high interobserver variability.
A Biography of the Eye: Development, Growth, Age

This is a new edition of the author's book, The Aging Eye , published in 1963. The interesting title reflects the author's thesis that gerontology, or the study of senescence, involves involutional changes in development beginning at birth at molecular, cellular, and systemic levels. The comprehensive nature of this book is indicated by inclusion of the material from 49 pages of references with most of the illustrations from these sources. After a general discussion of the several ways of looking at the process of aging, the biography of the eye begins with ocular embryology, the infant eye, growth, and senescent changes in the eyeball, uveal tract, lens, retina, brain, and responses to visual stimuli. The style and delightful vignettes make this presentation of a difficult subject worthy of the best English tradition. This book is a must for those investigators interested in any aspect of senescence in ocular tissues, or for
The Effects of the L / N‐Type Calcium Channel Blocker (Cilnidipine) on Sympathetic Hyperactive Morning Hypertension: Results From ACHIEVE‐ONE *

The Ambulatory Blood Pressure Control and Home Blood Pressure (Morning and Evening) Lowering By N‐Channel Blocker Cilnidipine (ACHIEVE‐ONE) trial is a large‐scale clinical study on blood pressure (BP) and pulse rate (PR) in the real world with use of cilnidipine, a unique L/N‐type Ca channel blocker, possessing a suppressive action on increased sympathetic activity in patients with essential hypertension. The effects of cilnidipine on morning hypertension were examined. The authors examined 2319 patients treated with cilnidipine for 12 weeks. Clinic systolic BP (SBP) decreased by 19.6 mm Hg from 155.0 mm Hg, whereas morning SBP decreased by 17.0 mm Hg from 152.9 mm Hg after 12‐week cilnidipine treatment. Cilnidipine reduced both morning SBP and PR more markedly in patients with higher baseline morning SBP (−3.2 mm Hg and −1.3 beats per minute in the first quartile of morning SBP, −30.9 mm Hg and −3.2 beats per minute in the fourth quartile), and also reduced both morning PR and SBP more markedly in patients with higher baseline morning PR (0.6 beats per minute and −15.6 mm Hg in <70 beats per minute, and −9.7 beats per minute and −20.2 mm Hg in ≥85 beats per minute). Cilnidipine significantly reduced BP and PR in hypertensive patients at the clinic and at home, especially with higher BP and PR in the morning. J Clin Hypertens (Greenwich). 2012; 00:00–00. ©2012 Wiley Periodicals, Inc.
Glossoplegia in a small cortical infarction

We recently observed a patient with obvious contralateral tongue deviation with minimal lower facial paresis caused by a small cortical infarction confirmed by MRI. The small cortical lesion, causing obvious tongue deviation in our patient, was located lateral to the precentral knob which is known as a reliable anatomical landmark for the motor hand area. We were able to localise the cortical area for tongue movement to the most lateral part of the precentral gyrus lateral to the precentral knob. A 63-year-old, right-handed man with a 1 year history of hypertension suddenly developed dysarthria. He was alert, …
The Impact of Secondary Condom Interventions on the Interpretation of Results from HIV Prevention Trials

Given the recent failure of a number of randomized trials to demonstrate effectiveness of proposed methods for prevention of sexual transmission of HIV, novel approaches to study design and analysis that address adherence and other post-randomization behaviors are of increasing interest. The inclusion of a mandatory condom use intervention in all randomized groups in such trials can significantly impact interpretation of study results, especially when levels of use observed in the study may differ from real world levels.We use quantitative examples and simulations to investigate this issue, focusing on effectiveness estimated by the standard intention to treat analysis approach. We also assess the application of recently developed methods for estimating the causal effect of treatment assignment, accounting for observed levels of condom use.Results show that observed levels of condom use may have substantial impacts on the conclusions drawn from standard analyses of prevention trials, with the most serious effects observed in studies with unblinded control groups. Causal estimation methods accounting for post-randomization behaviors can help clarify these impacts by focusing attention on effectiveness for controlled levels of condom use.Supplemental causal analyses that account for post-randomization condom use may provide useful information about possible efficacy that complement standard analyses. However, interpretation of results may be limited by the quality of available data on adherence behavior, and limited statistical power.
MiRNALet‐7a mediates prostate cancer PC‐3 cell invasion, migration by inducing epithelial‐mesenchymal transition through CCR7/MAPK pathway

Prostate cancer is one of the most common malignancies in older men. Recent evidence has demonstrated microRNA (miRNA) Let‐7a expression decreased in prostate cancer, while the expression of CC chemokine receptor type 7 (CCR7) increased. In this study, we investigated whether CCR7 overexpression was associated with a decrease in the expression of miRNA Let‐7a in invasion and metastasis of prostate cancer cell. Synthetic Let‐7a mimics and Let‐7a inhibitors were transfected into prostate cancer PC‐3 cells, respectively. Then Western blot was used to detect the expression of CCR7, ERK, p38, MMP‐9, and Epithelial‐Mesenchymal Transition (EMT)‐related proteins. Matrigel invasion assays were performed to assess the migratory and invasive activities of PC3 cells. To confirm the fact that 3′UTR of CCR7 is a direct target of Let‐7a, a luciferase assay for the reporter gene expressing the Let‐7a binding sites of CCR7 3′UTR was used. Synthetic Let‐7a mimics decreased prostate cancer cell migration and invasion, as well as the expression of CCR7, phospho‐p38, phospho‐ERK1/2, MMP‐9, N‐cadherin, and Snail in PC‐3 cells. The Let‐7a inhibitors reversed the effects of Let‐7a on PC‐3 cells. The 3′UTR of CCR7 was confirmed as a direct target of Let‐7a by using the luciferase assay. All findings demonstrated that Let‐7a/CCR7 axis regulated EMT progress in prostate cancer cells and mediated the tumor cell invasion and migration process via activation of P38/ERK signal pathway. Our results suggested that the therapeutic potential of Let‐7a as an antitumor and antimetastatic manager in prostate cancer and CCR7 may be regarded as a therapeutic target for the prostate cancer treatment.
The effect of stimulating massage of thigh muscles on knee joint position sense

Objectives: To examine the effects of stimulating massage given to the quadriceps, sartorial, gracile and hamstrings muscles on knee joint position sense (JPS). Study design: Two randomized groups in a crossover design. Subjects: Eighteen healthy subjects between 21 and 31 years old volunteered (12 women and six men). Methods: The JPS was measured three times on the right knee in both groups. In a crossover design, with 7 days washout, 18 subjects received stimulating massage of the right quadriceps, sartorial, gracile and hamstrings muscles for 10 min or rested as control between measures. The JPS was measured as a single-leg and double-leg test. To assess if stimulating massage improved the subject's ability to reproduce a joint position, absolute error (AE) was used as primary outcome measure. AE is the mean of the differences between the target angles and the subject's estimated angles excluding the largest observed difference. Results: In the single-leg experiment, a median difference in AE between groups was 1.75° with a 95% confidence interval of 0.59–2.91°. This was found to be significant (p=0.012), indicating a positive effect of the massage on the JPS. No significant difference was found in the double-leg experiment. Conclusion: The results from this study show that stimulating massage diminishes the intra-individual error in relation to the repeating measurements of JPS. This may have implications for the choice of massage in order to improve subjects with decreased JPS following muscle, joint or neurological pathologies.
No climate justice without gender justice: an overview of the issues

Both climate change itself and related policies are likely to have wide-ranging effects on gender relations, especially in developing countries. Poor women face many gender-specific barriers that limit their ability to cope with and adapt to a changing climate; these must be removed in the interests of both gender equity and adaptation efficiency. At the same time, gender analysis should be integral to the appraisal of public policies designed to reduce carbon emissions. To date, gender issues have hardly figured in the international policy discourse, including the UN Framework Convention on Climate Change and its Kyoto Protocol. However, this may be changing thanks to feminist lobbying and the increasing involvement of gender specialists in this field. There is a lot at stake; the international post-2012 Kyoto Protocol agreement will have enormous implications for gender equality.