Miracle-dz/UniFAR-FTUs huggingface dataset:
Seco-pregnane steroids target the subgenomic RNA of alphavirus-like RNA viruses

Plants have evolved multiple mechanisms to selectively suppress pathogens by production of secondary metabolites with antimicrobial activities. Therefore, direct selections for antiviral compounds from plants can be used to identify new agents with potent antiviral activity but not toxic to hosts. Here, we provide evidence that a class of compounds, seco-pregnane steroid glaucogenin C and its monosugar-glycoside cynatratoside A of Strobilanthes cusia and three new pantasugar-glycosides of glaucogenin C of Cynanchum paniculatum, are effective and selective inhibitors to alphavirus-like positive-strand RNA viruses including plant-infecting tobacco mosaic virus (TMV) and animal-infecting Sindbis virus (SINV), eastern equine encephalitis virus, and Getah virus, but not to other RNA or DNA viruses, yet they were not toxic to host cells. In vivo administration of the compounds protected BALB/c mice from lethal SINV infection without adverse effects on the mice. Using TMV and SINV as models, studies on the action mechanism revealed that the compounds predominantly suppress the expression of viral subgenomic RNA(s) without affecting the accumulation of viral genomic RNA. Our work suggested that the viral subgenomic RNA could be a new target for the discovery of antiviral drugs, and that seco-pregnane steroid and its four glycosides found in the two medicinal herbs have the potential for further development as antiviral agents against alphavirus-like positive-strand RNA viruses.
Life Goes On: Psychosocial Suffering from war and healing pathways in northern Rwanda.

This thesis explores the ways in which local communities in Musanze, northern Rwanda, heal psychosocial suffering from the war period between 1990 and 2000 in the context of limited humanitarian aid. Employing a narrative approach, it unpacks experience of psychosocial suffering, elaborates the ways in which communities heal themselves, and describes the meaning of ‘healing’ in the light of local views of morality, life and death. Qualitative analysis drew on participant observation, in-depth interviews, and focus-group discussions based on ten months of ethnographic fieldwork, which built on prior life and work experience in the field over two years. Findings first describe local conceptualizations of psychosocial sufferings. These fell on a spectrum constructed by the degree of social disconnection reported by participants and how far their thoughts and memories were oriented towards a wounded past. A key element of suffering was the literal ‘unspeakability’ of many wounds due to politically-sensitive circumstances. This related to difficulties in making sense of what they have experienced. Narratives of healing pathways described a common theme of leaving the past behind and going forward to the future through participation in different communities, including church-based groups, traditional mutual-saving groups, and neighbourhood relationships. In the context of the unspeakability of many wounds, communities provided alternative ways of healing from ‘speaking’ of wounds directly. These include: allowing members to make sense of their sufferings through religious and traditional activities, everyday-life practices, and life-event ceremonies. The thesis highlights that, in this setting, healing is not conceptualized as ‘recovery’ as assumed by Western theories, but rather, as a trajectory of ‘life goes on’: that is, that time continues into the future. In this emic experience of healing, the focus is not on traumatic time but on time ‘being lived’ as part of life, and a series of lives handed over from generation to generation, through sharing everyday life and significant life events. In other words, healing can take place through social connection in a wider time-scale than trauma.
Differences in help seeking rates after brief intervention for alcohol use disorders in general practice patients with and without comorbid anxiety or depressive disorders

Aims: To examine, if the utilization of help for problematic drinking after brief intervention (BI) differs between general practice (GP) patients with and without comorbid depression or anxiety disorders. Methods: Longitudinal data of 374 GP patients, who met the diagnostic criteria of alcohol dependence or abuse according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM‐IV) and criteria of at‐risk drinking or binge drinking, were drawn from a randomized controlled BI study. Participants were randomly allocated to either a control or one of two intervention groups, receiving a series of alcohol related BI. Of the sample, 88 participants were diagnosed with comorbid anxiety and/or depressive disorders. At 12‐months follow‐up, differences in utilization of formal help for drinking problems were assessed between comorbid and non‐comorbid individuals. Results: BI were significantly related to an increase in utilization of formal help in non‐comorbid patients (χ2 = 4.54; df = 1; p < 0.05) but not in comorbid individuals (χ2 = 0.40; df = 1; p = 0.60). In a logistic regression analysis, comorbidity [odds ratio (OR) = 1.81; 95% confidence interval (CI) = 1.14–2.88; p = 0.01) and previous help seeking (OR = 15.98; CI = 6.10–41.85; p < 0.001) were found to be positive predictors for utilization of formal help. Conclusion: BIs do not seem to significantly support help‐seeking in the comorbid. As comorbid anxiety and depression constitute a positive predictor for help‐seeking, individuals with problematic drinking and comorbid anxiety or depressive disorders might benefit from more specialized support exceeding the low level of BI. Copyright © 2008 John Wiley & Sons, Ltd.
Total hip arthroplasty and hemiarthroplasty in mobile, independent patients with a displaced intracapsular fracture of the femoral neck. A randomized, controlled trial.

BACKGROUND Hemiarthroplasty and total hip arthroplasty are commonly used to treat displaced intracapsular fractures of the femoral neck, but each has disadvantages and the optimal treatment of these fractures remains controversial. METHODS In the present prospectively randomized study, eighty-one patients who had been mobile and lived independently before they had sustained a displaced fracture of the femoral neck were randomized to receive either a total hip arthroplasty or a hemiarthroplasty. The mean age of the patients was seventy-five years. Outcome was assessed with use of the Oxford hip score, and final radiographs were assessed. RESULTS After a mean duration of follow-up of three years, the mean walking distance was 1.17 mi (1.9 km) for the hemiarthroplasty group and 2.23 mi (3.6 km) for the total hip arthroplasty group, and the mean Oxford hip score was 22.3 for the hemiarthroplasty group and 18.8 for the total hip arthroplasty group. Patients in the total hip arthroplasty group walked farther (p=0.039) and had a lower (better) Oxford hip score (p=0.033) than those in the hemiarthroplasty group. Twenty of thirty-two living patients in the hemiarthroplasty group had radiographic evidence of acetabular erosion at the time of the final follow-up. None of the hips in the hemiarthroplasty group dislocated, whereas three hips in the total hip arthroplasty group dislocated. In the hemiarthroplasty group, two hips were revised to total hip arthroplasty and three additional hips had acetabular erosion severe enough to indicate revision. In the total hip arthroplasty group, one hip was revised because of subsidence of the femoral component. CONCLUSIONS Total hip arthroplasty conferred superior short-term clinical results and fewer complications when compared with hemiarthroplasty in this prospectively randomized study of mobile, independent patients who had sustained a displaced fracture of the femoral neck.
A generalized focused information criterion for GMM

This paper proposes a criterion for simultaneous generalized method of moments model and moment selection: the generalized focused information criterion (GFIC). Rather than attempting to identify the “true” specification, the GFIC chooses from a set of potentially misspecified moment conditions and parameter restrictions to minimize the mean squared error (MSE) of a user‐specified target parameter. The intent of the GFIC is to formalize a situation common in applied practice. An applied researcher begins with a set of fairly weak “baseline” assumptions, assumed to be correct, and must decide whether to impose any of a number of stronger, more controversial “suspect” assumptions that yield parameter restrictions, additional moment conditions, or both. Provided that the baseline assumptions identify the model, we show how to construct an asymptotically unbiased estimator of the asymptotic MSE to select over these suspect assumptions: the GFIC. We go on to provide results for postselection inference and model averaging that can be applied both to the GFIC and various alternative selection criteria. To illustrate how our criterion can be used in practice, we specialize the GFIC to the problem of selecting over exogeneity assumptions and lag lengths in a dynamic panel model, and show that it performs well in simulations. We conclude by applying the GFIC to a dynamic panel data model for the price elasticity of cigarette demand.
A cohort mortality study of U.K. carbon black workers, 1951-1996.

BACKGROUND Carbon black, a powdered form of elemental carbon is used in the manufacture of rubber products, paints, plastics, and inks. In 1974, the Health and Safety Executive initiated a cohort mortality study on possible carcinogenic effects on carbon black workers. METHODS The mortality of a cohort of 1,147 male manual workers from five U.K. factories manufacturing carbon black was investigated for the period 1951-1996. All subjects were employed in the carbon black industry for 12 months or more, and all were first employed before 1975. Limited work histories were used to calculate estimates of individual cumulative exposure to carbon black, using a job-exposure matrix derived by the study team. RESULTS Based on serial rates for the general population of England and Wales, significantly elevated mortality was observed in the main study cohort for all causes (Obs 372, Exp 328.7, SMR 113, P < 0.05) and for lung cancer (Obs 61, Exp 35.3, SMR 173, P < 0.001). There were highly elevated lung cancer SMRs at two of the factories, and unexceptional SMRs at the remaining three factories. There was no indication of lung cancer SMRs increasing with period from first employment. Poisson regression analyses failed to find significant trends of lung cancer risks increasing either with cumulative exposure to carbon black (4 levels) or with duration of employment at the participating factories (4 levels). CONCLUSIONS Confident interpretation of the elevated SMRs found for lung cancer in two of the factory subcohorts is not possible but the study has been unable to link cumulative exposure to carbon black with elevated risks of lung cancer.
Effect of chronic corticosterone application on depression‐like behavior in C57BL/6N and C57BL/6J mice

Many studies using genetic mouse models are performed with animals on either one of the two closely related genetic backgrounds, C57BL/6J or C57BL/6N. These strains differ only in a few genetic loci, but have some phenotypic differences that also affect behavior. In order to determine the effects of chronic stress hormone exposure, which is relevant for the pathogenesis of psychiatric disorders, we investigated here the behavioral manifestations of long‐term increase in corticosterone levels. Thus, male mice from both sub‐strains were subcutaneously implanted with corticosterone (20 mg) or placebo pellets that released the hormone for a period of 21 days and resulted in significantly elevated plasma corticosterone levels. Corticosterone significantly increased food intake in B6N, but not in B6J mice. At various time points after pellet implantation, we performed tests relevant to activity and emotional behaviors. B6J mice displayed a generally higher activity in the home cage and the open field. Corticosterone decreased the activity. In B6N mice, corticosterone also decreased sucrose preference, worsened the coat state and increased forced swim immobility, while it had no effect in the B6J strain. Altogether, these results indicate that B6N mice are more sensitive to some of the effects of chronic corticosterone treatment than B6J mice.
Concentration‐dependent transitions govern the subcellular localization of islet amyloid polypeptide

Islet amyloid polypeptide (IAPP) is a peptide hormone cosecreted with insulin by pancreatic β‐cells. In type II diabetes, IAPP aggregates in a process that is associated with β‐cell dysfunction and loss of β‐cell mass. The relationship between IAPP's conformational landscape and its capacity to mediate cell death remains poorly understood. We have addressed these unknowns by comparing the cytotoxic effects of sequence variants with differing α‐helical and amyloid propensities. IAPP was previously shown to oligomerize cooperatively on binding to lipid bilayers. Here, comparable transitions are evident in cell culture and are associated with a change in subcellular localization to the mitochondria under toxic conditions. Notably, we find that this toxic gain of function maps to IAPP's capacity to adopt aggregated membrane‐bound α‐helical, and not β‐sheet, states. Our findings suggest that upon α‐helical mediated oligomerization, IAPP acquires cell‐penetrating peptide (CPP) properties, facilitating access to the mitochondrial compartment, resulting in its dysfunction. —Magzoub, M. Miranker, A. D. Concentration‐dependent transitions govern the subcellular localization of islet amyloid polypeptide. FASEB J. 26, 1228‐1238 (2012). www.fasebj. org
Delineating CSF-1-dependent regulation of myeloid cell diversity in tumors

Myeloid cells contribute to increased malignancy and poor prognosis in breast cancer. We demonstrate that anti-CSF-1R therapy depletes a cell population sharing characteristics of tumor-associated macrophages (TAMs) and dendritic cells (DCs). Intravital imaging combined with cellular characterization has refined our understanding of anti-CSF-1R therapy on the tumor microenvironment.
Orphan G Protein-coupled Receptor, GPR41, Induces Apoptosis via a p53/Bax Pathway during Ischemic Hypoxia and Reoxygenation*

Orphan receptors that couple to G protein without known ligands are considered to relate directly to drug discovery. Here, we examine the expression of various orphan receptors in H9c2 cells during ischemic hypoxia and reoxygenation. Among orphan receptors examined, the level of G protein-coupled receptor 41( GPR41 ) mRNA increases significantly, with a peak at 2 h after reoxygenation, and recovers to the control level by 3 h after reoxygenation. The level of glyceraldehyde-3-phosphate dehydrogenase mRNA used as an internal control remains almost constant. The levels of c-fos and c-junmRNA increase significantly with ischemic hypoxia and reoxygenation. The transfection of GPR41 into H9c2 cells results in a significant decrease in cell number, with DNA fragmentation observed byin vitro and in situ assay. The amount of p53 protein increases significantly in the nuclei of cells expressing GPR41, accompanying an increase in the transcriptional activity of p53. Consistent with the activation of p53, the level of baxmRNA is significantly increased, which leads to an increase in Bax protein. Furthermore, the expression of a deletion mutant of a GPR41, which lacks the G protein binding site and shows an attenuation of intracellular phosphorylation signals to H9c2 cells, inhibits cell death and the increase in p53 protein within 24 h after reoxygenation. These observations demonstrate that GPR41 is a novel receptor that activates p53 leading to apoptosis during reoxygenation after ischemic hypoxia in H9c2 cells. We have designated GPR41 as the hypoxia-induced apoptosis receptor, HIA-R.
Capital punishment in precolonial Africa: the authenticity challenge

ABSTRACT The modern debate over death penalty abolition in Sub-Saharan Africa frequently references the precolonial period. Has the death penalty truly existed since time immemorial, or is it largely a European imposition? The extent to which precolonial societies used capital punishment is difficult to discern, as many of the anthropological and legal sources that document this period were influenced by colonialism. These sources nonetheless show that the use of capital punishment in the precolonial period was tied to notions of political authority and the spirit world, though legal procedures and even methods of execution varied enormously among societies. This article considers the reliability problems of the extant sources and attempts to make tentative conclusions as to the existence of the death penalty prior to the onset of European rule, bearing in mind that these conclusions are not exhaustive or even necessarily representative of the continent's diversity.
Chloroquine dissociation of antigen‐antibody complexes

We have investigated a method using the quinoline derivative chloroquine diphosphate (200 mg/ml, pH 5.0) to dissociate antibody without denaturing red blood cell antigens. All samples treated with chloroquine diphosphate demonstrated some dissociation of the coating immunoglobulin, and in most cases, the ability to dissociate the coating immunoglobulin was related to the strength of the direct antiglobulin test (DAT). Complete dissociation of antibody was observed in 22 of 40 strongly in vitro sensitized samples and 47 of 56 in vivo sensitized specimens, with no apparent loss of ABH, Rh, MNSs, P1, Lewis, Kell, Duffy, or Kidd antigens. We have found the chloroquine dissociation technique to be of value in the examination of red blood cells with a positive DAT, either for the qualitative or quantitative expression of antigens.
Anesthesia Care Transitions and Risk of Postoperative Complications

BACKGROUND:A patient undergoing surgery may receive anesthesia care from several anesthesia providers. The safety of anesthesia care transitions has not been evaluated. Using unconditional and conditional multivariable logistic regression models, we tested whether the number of attending anesthesiologists involved in an operation was associated with postoperative complications. METHODS:In a cohort of patients undergoing elective colorectal surgical in an academic tertiary care center with a stable anesthesia care team model participating in the American College of Surgeons National Surgical Quality Improvement Program, using unconditional and conditional multivariable logistic regression models, we tested adjusted associations between numbers of attending anesthesiologists and occurrence of death or a major complication (acute renal failure, bleeding that required a transfusion of 4 units or more of red blood cells within 72 hours after surgery, cardiac arrest requiring cardiopulmonary resuscitation, coma of 24 hours or longer, myocardial infarction, unplanned intubation, ventilator use for 48 hours or more, pneumonia, stroke, wound disruption, deep or organ-space surgical-site infection, superficial surgical-site infection, sepsis, septic shock, systemic inflammatory response syndrome). RESULTS:We identified 927 patients who underwent elective colectomy of comparable surgical intensity. In all, 71 (7.7%) patients had major nonfatal complications or death. One anesthesiologist provided care for 530 (57%) patients, 2 anesthesiologists for 287 (31%), and 3 or more for 110 (12%). The number of attending anesthesiologists was associated with increased odds of postoperative complication (unadjusted odds ratio [OR] = 1.52, 95% confidence interval [CI] 1.18–1.96, P = 0.0013; adjusted OR = 1.44, 95% CI 1.09–1.91, P = 0.0106). In sensitivity analyses, occurrence of a complication was significantly associated with the number of in-room providers, defined as anesthesia residents and nurse anesthetists (adjusted OR = 1.39, 95% CI 1.01–1.92, P = 0.0446) and for all anesthesia providers (adjusted OR = 1.58, 95%CI 1.20–2.08, P = 0.0012). Findings persisted across multiple, alternative adjustments, sensitivity analyses, and conditional logistic regression with matching on operative duration. CONCLUSIONS:In our study, care by additional attending anesthesiologists and in-room providers was independently associated with an increased odds of postoperative complications. These findings challenge the assumption that anesthesia transitions are care neutral and not contributory to surgical outcomes.
Effective Heart Disease Detection Based on Quantitative Computerized Traditional Chinese Medicine Using Representation Based Classifiers

At present, heart disease is the number one cause of death worldwide. Traditionally, heart disease is commonly detected using blood tests, electrocardiogram, cardiac computerized tomography scan, cardiac magnetic resonance imaging, and so on. However, these traditional diagnostic methods are time consuming and/or invasive. In this paper, we propose an effective noninvasive computerized method based on facial images to quantitatively detect heart disease. Specifically, facial key block color features are extracted from facial images and analyzed using the Probabilistic Collaborative Representation Based Classifier. The idea of facial key block color analysis is founded in Traditional Chinese Medicine. A new dataset consisting of 581 heart disease and 581 healthy samples was experimented by the proposed method. In order to optimize the Probabilistic Collaborative Representation Based Classifier, an analysis of its parameters was performed. According to the experimental results, the proposed method obtains the highest accuracy compared with other classifiers and is proven to be effective at heart disease detection.
Metal Proportion Optimization of Annular Through-Silicon via Considering Temperature and Keep-Out Zone

For annular through-silicon via (TSV)-based 3-D integrated circuits (3-D ICs), a greater TSV metal proportion of annular TSV leads to lower temperature but induces larger keep-out zone (KOZ). In this paper, the figure of merit (FOM) tradeoff model between temperature and KOZ is proposed to obtain the optimal metal proportion of annular TSV. First, the analytical models of the temperature of annular TSV-based 3-D IC and the KOZ induced by annular TSV are given, respectively, and both of them are verified by ANSYS software. Second, based on the analytical models, the FOM model is proposed. Then, the effects of total radius, material, and insertion density of annular TSV on FOM and optimal metal proportion are analyzed in detail. It is concluded that, the optimal metal proportion of annular TSV is approximately 0.3 with large ranges of the total radius and density of annular TSV, and various materials filled in annular TSV.