Miracle-dz/UniFAR-FTUs huggingface dataset:
Dermal vascular IgA deposits in IgA nephropathy secondary to alcohol abuse

Skin, kidney and liver samples were investigated from 103 people with evidence of alcohol abuse at forensic autopsy. The diagnosis of alcohol abuse was based on clinical history, post mortem blood alcohol level and liver pathology. The findings confirmed the frequent widespread vascular IgA deposition in individuals with evidence of alcohol abuse. The frequency of IgA deposition in superficial small vessels of the dermis was not significantly different between individuals with IgA nephritis (16/85) and without such pathology (7/38). Based on these results, it can be inferred that had a pre‐mortem skin biopsy been performed, it would not have had clinical usefulness in predicting the renal disease.
Exploring the Origins of the Human Brain through Molecular Evolution

The emergence of the human brain is one of evolution’s most compelling mysteries. With its singular importance and astounding complexity, understanding the forces that gave rise to the human brain is a major undertaking. Recently, the identification and publication of the complete genomic sequence of humans, mice, chimpanzees, and macaques has allowed for large-scale studies looking for the genic substrates of this natural selection. These investigations into positive selection, however, have generally produced incongruous results. Here we consider some of these studies and their differences in methodologies with an eye towards how they affect the results. We also clarify the strengths and weaknesses of each of these approaches and discuss how these can be synthesized to develop a more complete understanding of the genetic correlates behind the human brain and the selective events that have acted upon them.
3′-Azido-2′,3′-Dideoxythymidine (Zidovudine) Uptake Mechanisms in T Lymphocytes

The nucleoside reverse transcriptase inhibitors (NRTIs) make up a family of antiretroviral drugs widely used in the treatment of HIV-1 infection. Human concentrative nucleoside transporters and equilibrative nucleoside transporters, encoded by SLC28 and SLC29 gene families, respectively, are known to be involved in the uptake of a variety of nucleoside analogues used in anticancer treatment. We therefore examined whether SLC28- and SLC29-encoded proteins contribute to the entry of these NRTIs into the human leukaemic T-cell line Molt-4. Cis-inhibition experiments demonstrated that nucleoside transporters have a negligible role in antiviral drug uptake. Moreover, the previously identified 3′-azido-2′,3′-dideoxythymidine (zidovudine; AZT) carriers, organic anion transporters (organic anion transporter [hOATs], members of the SLC22 gene family) have not been detected in T cells, either functionally or at the mRNA level, thus ruling out a role for hOATs in antiviral drug uptake in these cells. Nevertheless, the data provided here argue against the hypothesis of simple diffusion across the plasma membrane as the unique mechanism of AZT uptake. Actually, this pyrimidine derivative seems to have a temperature-sensitive route of entrance, a finding that, along with the evidence that, AZT inhibits its own uptake and its transport into phytohaemagglutinin-stimulated peripheral blood mononuclear cells is upregulated, strongly support the idea that AZT uptake into T-cells is associated with a mediated and regulated, transport mechanism.
Application of a nonlinear adaptive controller to a 6 DOF parallel manipulator

Nonlinear adaptive control schemes for robotic manipulators or new types of high speed machine tools with nonlinear dynamics are well suited to keep the tracking errors low, even at high speeds. Their application however requires fast microprocessors and an operating system that allows implementing the control algorithms as hard real-time tasks. The paper presents the implementation of a nonlinear model-based manipulator controller with adaptation algorithms on a new generation real-time operating system (RTOS) called XOberon. This RTOS goes beyond the established concepts, like interruptor priority-driven scheduling, bringing in new programming paradigms, such as deadline-driven scheduling. The superiority of this controller when applied to a fast 6 DOF parallel manipulator is finally shown by comparing its tracking performance with the one obtained using conventional linear controllers.
A Connection between Feed-Forward Neural Networks and Probabilistic Graphical Models

Two of the most popular modelling paradigms in computer vision are feed-forward neural networks (FFNs) and probabilistic graphical models (GMs). Various connections between the two have been studied in recent works, such as e.g. expressing mean-field based inference in a GM as an FFN. This paper establishes a new connection between FFNs and GMs. Our key observation is that any FFN implements a certain approximation of a corresponding Bayesian network (BN). We characterize various benefits of having this connection. In particular, it results in a new learning algorithm for BNs. We validate the proposed methods for a classification problem on CIFAR-10 dataset and for binary image segmentation on Weizmann Horse dataset. We show that statistically learned BNs improve performance, having at the same time essentially better generalization capability, than their FFN counterparts.
Tobacco Cessation and the Household Budget: A Longitudinal Analysis of Consumption and Heterogeneity in the United States

Tobacco Cessation and the Household Budget: A Longitudinal Analysis of Consumption and Heterogeneity in the United States By Erin S. Rogers Advisor: William T. Gallo, PhD Objectives: This dissertation was designed to: (1) estimate the relationships between recent, longterm, and relapsed tobacco cessation and dollars spent on non-tobacco goods among households in the U.S., (2) estimate the relationships between recent, long-term, and relapsed tobacco cessation and the budget shares allocated to non-tobacco goods among households in the U.S., and (3) to identify and characterize unobserved heterogeneity in the relationship between tobacco cessation and dollars spent on alcohol and food. Methods: Using 2006-2012 Consumer Expenditure Survey (CES) data, a cohort of 6,739 tobaccoconsuming households was created and followed for four quarters. Households were categorized during the fourth quarter as having: (1) recent tobacco cessation, (2) long-term cessation, (3) relapsed cessation or (4) no cessation. Generalized linear models and fractional logistic regression were used to compare the fourth quarter expenditures and budget shares of eight categories (alcohol, food at home, food away from home, housing, health care, transportation, entertainment and other) between the no cessation households and those with recent, long-term or relapsed cessation. All models controlled for potential confounding variables, including
In vivo regulation of tissue‐specific and LPS‐inducible expression of the Drosophila Cecropin genes

The inducible production of antibacterial cecropins in Drosophila fat body and haemocytes is controlled at the level of transcriptional induction. We demonstrate using germ‐line transformation that a short, highly conserved, DNA region, including the insect κB motif, is necessary for tissue‐specific expression in larvae and adults. Quantitative measurements of reporter gene activity in extracts from transgenic larvae confirmed the requirement of this proximal region for LPS‐inducible expression in vivo. Transient expression in a blood cell line indicates the existence of positively acting elements further upstream of the conserved region. Furthermore, our in vivo data suggests that the distal upstream region contains negatively acting element(s).
Can Individualized Health Care Plans Help Increase Continence in Children With Dysfunctional Elimination Syndrome?

School-age children with dysfunctional elimination syndrome (DES) do not always have school support for their treatment plans, including an every 2-hr voiding schedule. The objective of this study was to increase school support of treatment plans by allowing access to bathrooms, thereby improving continence. An eight-question survey about bathroom access at schools was given to parents at baseline. The author contacted school nurses requesting that treatment plans be incorporated into individual health plans (IHPs) with teacher support of the IHP. Six weeks later, school nurses were contacted and parents completed a postintervention survey to determine whether IHPs were supported by teachers. Voiding diaries were used to document continence. Seventeen parents completed the survey at baseline, and 13 children were enrolled in the intervention. After the intervention, 100% of the children had IHPs and teacher support of treatment plans. Ninety-two percent had increased continence. IHPs improved teacher support of children’s treatment plans and improved their continence.
Splenic accumulation of interleukin-3-dependent hematopoietic cells in Friend erythroleukemia

Interleukin-3-dependent hematopoietic stem cells commonly accumulate in spleens of mice infected with leukemia viruses. To study their origins, a molecularly tagged helper-free Friend spleen focus-forming virus was used to produce erythroleukemias. Uninfected interleukin-3-dependent basophil-mast cell progenitors coproliferated amidst the spleen focus-forming virus-infected leukemic cells. Splenic proliferation of normal stem cells is apparently a host response to leukemogenesis, and we propose that it may contribute to certain retroviral diseases.
Blockade of MCP-1/CCR4 signaling-induced recruitment of activated regulatory cells evokes an antitumor immune response in head and neck squamous cell carcinoma

FoxP3+ regulatory T (Treg) cells have diverse functions in the suppression of antitumor immunity. We show that FoxP3hiCD45RA−CD4+ Treg cells [activated Treg (aTreg) cells] are the predominant cell population among tumor-infiltrating FoxP3+ T cells, and that high aTreg cell-infiltrating content is associated with reduced survival in patients with head and neck squamous cell carcinoma (HNSCC). In vitro studies have demonstrated that aTreg cells can suppress tumor-associated antigen (TAA) effector T cell immune responses in HNSCC. Moreover, C-C chemokine receptor 4 (CCR4) was specifically expressed by aTreg cells in the peripheral blood of HNSCC patients. Using a RayBiotech human chemokine antibody array, we showed that monocyte chemoattractant protein-1 (MCP-1), an endogenous CCR4-binding ligand, was specifically upregulated in the HNSCC microenvironment compared to the other four CCR4-binding ligands. Blocking MCP-1/CCR4 signaling-induced aTreg cell recruitment using a CCR4 antagonist evoked antitumor immunity in mice, and lead to inhibition of tumor growth and prolonged survival. Therefore, blocking aTreg cell trafficking in tumors using CCR4-binding agents may be an effective immunotherapy for HNSCC.
Medical Students’ Perspectives on Implementing Curriculum Change at One Institution

Training physicians to be effective practitioners throughout their careers begins in undergraduate medical education with particular focus on self-directed inquiry, professional and interprofessional development, and competency-based assessment. A select number of medical schools are restructuring their curricula by placing the student at the center of content delivery to enhance the learning experience. While this restructuring may benefit the adult learner, administrators often make assumptions about how students will perceive and respond to such innovative and unfamiliar educational concepts. This can create a disconnect between students and their curriculum. Administrative mindfulness of student experiences is needed to ensure successful implementation of curricular change, facilitate the transition from old to new modalities, and train competent physician graduates. Vanderbilt University School of Medicine (VUSM) recently completed a curriculum update, and student representatives have been essential participants in the transition, from the earliest stages in preplanning to rapid-cycle feedback as the curriculum runs. Two of the authors are members of VUSM’s Student Curriculum Committee, which facilitates gathering and relaying student feedback to the administration. Drawing from their experiences, five specific considerations to address and manage when implementing student-centered curricular change are presented: (1) Communicate the rationale, (2) acknowledge anxiety, (3) adjust extracurricular leadership roles, (4) manage “The Bulge” of learners in the clinical environment, and (5) foster ongoing collaboration of students and administrators. For each consideration, examples and proposed solutions are provided.
Human Cytomegalovirus Inhibits Cytokine-Induced Macrophage Differentiation

ABSTRACT Human cytomegalovirus (HCMV) infection in immunocompromised patients is associated with impaired immunological function. Blood monocytes, which differentiate into macrophage effector cells, are of central importance for immune reactivity. Here, we demonstrate that HCMV transiently blocks cytokine-induced differentiation of monocytes into functionally active phagocytic macrophages. In HCMV-treated cultures, the cells had classical macrophage markers but lacked the classical morphological appearance of macrophages and had impairments in migration and phagocytosis. Even at very low multiplicities of infection, macrophage differentiation was almost completely inhibited. The inhibition appeared to be mediated by a soluble factor released upon viral treatment of monocytes. Human immunodeficiency virus or measles virus had no such effects. These findings suggest that HCMV impairs immune function by blocking certain aspects of cytokine-induced differentiation of monocytes and demonstrate an efficient pathway for this virus to evade immune recognition that may have clinical implications for the generalized immunosuppression often observed in HCMV-infected patients.
Link Between Immune Cell Infiltration and Mitochondria‐Induced Cardiomyocyte Death During Acute Cardiac Graft Rejection

Acute cardiac graft rejection (ACGR) is associated with cardiomyocyte apoptosis. We investigated the respective role of the Fas/FasL and mitochondrial permeability transition pore (mPTP) pathways in cardiomyocyte apoptosis accompanying ACGR. Heterotopic cardiac transplantations were performed in 7–9‐week old C57BL6 or C3H mice. Wild type or Fas‐deficient (lpr) mice underwent syngeneic (GS) or allogeneic (GA) transplantation, and received either saline or NIM811, a specific inhibitor of the mPTP. At day 5, we assessed ACGR by histology, cardiomyocyte apoptosis by caspase‐3 activity and cytochrome c release, Ca2+‐induced mPTP opening by a potentiometric approach, and expression of Fas, FasL, TNFα, perforin, granzyme using RT‐PCR. Myocardial infiltration of CD8+ T lymphocytes was performed by immunohistochemistry. Allogenic transplantation increased infiltration of inflammatory cells, upregulated FasL, perforin, granzyme, and TNFα, favored Ca2+‐induced mPTP opening and increased caspase‐3 activity and cytochrome c release in WT grafts. NIM811, but not Fas‐deficiency, significantly reduced all these effects. NIM811 also limited infiltration of CD8+ into WT and lpr transplants. These data suggest that the mPTP pathway plays a major role in cardiomyocyte apoptosis associated with ACGR. Inhibition of mPTP opening may attenuate cardiomyocyte apoptosis either directly or indirectly via a limitation of CD8+ T‐cell activation.
HIV neuropathy in South Africans: Frequency, characteristics, and risk factors

The purpose was to estimate the frequency, characteristics, and risk factors of HIV‐associated distal sensory polyneuropathy (DSP) among South Africans who attend an urban community‐based clinic. In a cross‐sectional study, neuropathy status was determined in 598 HIV‐infected adults using validated tools (Brief Peripheral Neuropathy Screen and a modified version of the Total Neuropathy Score) to categorize subjects as DSP versus no DSP. Symptomatic DSP (SDSP) required the presence of at least two neuropathic signs together with symptoms. Clinical, anthropometric, and laboratory evaluations were prospectively performed. CD4 counts, antiretroviral therapy (ART), and questionnaires regarding previous tuberculosis (TB) and alcohol exposure were collected retrospectively. Approximately half (49%) of the study population were diagnosed with DSP, and 30% of the study population were diagnosed with SDSP. In multivariate analyses the odds ratio (OR) (95% confidence interval) of DSP were independently associated with ART use (OR 1.7, 1.0–2.9), age (per 10 year increment) (OR 1.7, 1.4–2.2), and prior TB (OR 2.0, 1.3–3.0). Pain or paresthesias were reported as moderately severe by 70% of those with SDSP. Stavudine use was significantly associated with DSP. DSP is a clinically significant problem in urban HIV‐infected Africans. Our findings raise the possibility that the incidence of DSP may be reduced with avoidance of stavudine‐containing regimens in older subjects, especially with a history of prior TB infection. Muscle Nerve, 2010
Sleep physiology predicts memory retention after reactivation

Both sleep and future relevance influence memory consolidation; however, limited research has investigated their role in memory reconsolidation. We manipulated the future relevance of both stable and labile memories in need of reconsolidation. Two groups learned two blocks of syllable pairs on one evening and were told they would be tested on one of the blocks later. On the second evening, one group (Labile) received reminders designed to return their memories of syllable pairs to a labile state, while a second group (Stable) received reminders designed to leave these memories in a stable state. No significant differences in memory retention were found between blocks or groups the following morning. Frontal delta (0.5–4 Hz) electroencephalographic power during Stage 2 sleep correlated positively with retention of future‐relevant material exclusively in the Labile group. Central theta (4–8 Hz) electroencephalographic power during rapid eye movement (REM) sleep correlated positively with the extent to which the Labile group selectively retained future‐relevant material. These relationships suggest that sleep‐dependent processes are involved in an economical reprocessing of memories beyond the initial stages of consolidation.
Incidence of hospitalization due to community-acquired rotavirus infection: a 12-year study (1996–2008)

SUMMARY The incidence of hospitalization for acute gastroenteritis (AGE) is a useful parameter to assess the utility of the new rotavirus vaccines in high-income countries. Children hospitalized for AGE were identified by searching hospital discharge data and the records of the microbiology laboratory of Hospital Donostia. Rotavirus antigen was investigated in 96·1% of the 1114 children aged 1 month to <5 years hospitalized for AGE in the study period. Nearly 40% were rotavirus positive (44·9% of the 798 children aged 1 month to <2 years), with G1[P8] being the predominant genotype. The mean annual incidence rate of hospitalization due to rotavirus AGE was 29·8 and 63·7 cases/10 000 inhabitants in the <5 and <2 years age groups, respectively, in 1996–1999, decreasing to 13·6 and 27·4 cases/10 000 inhabitants in <5 and <2 years age groups, respectively, in 2002–2005 (P<0·001). This decrease coincided with a significant increase in the consumption of oral rehydration solutions.
Engineered Retargeting of Viral RNA Replication Complexes to an Alternative Intracellular Membrane

ABSTRACT Positive-strand RNA virus replication complexes are universally associated with intracellular membranes, although different viruses use membranes derived from diverse and sometimes multiple organelles. We investigated whether unique intracellular membranes are required for viral RNA replication complex formation and function in yeast by retargeting protein A, the Flock House virus (FHV) RNA-dependent RNA polymerase. Protein A, the only viral protein required for FHV RNA replication, targets and anchors replication complexes to outer mitochondrial membranes in part via an N-proximal sequence that contains a transmembrane domain. We replaced the FHV protein A mitochondrial outer membrane-targeting sequence with the N-terminal endoplasmic reticulum (ER)-targeting sequence from the yeast NADP cytochrome P450 oxidoreductase or inverted C-terminal ER-targeting sequences from the hepatitis C virus NS5B polymerase or the yeast t-SNARE Ufe1p. Confocal immunofluorescence microscopy confirmed that protein A chimeras retargeted to the ER. FHV subgenomic and genomic RNA accumulation in yeast expressing ER-targeted protein A increased 2- to 13-fold over that in yeast expressing wild-type protein A, despite similar protein A levels. Density gradient flotation assays demonstrated that ER-targeted protein A remained membrane associated, and in vitro RNA-dependent RNA polymerase assays demonstrated an eightfold increase in the in vitro RNA synthesis activity of the ER-targeted FHV RNA replication complexes. Electron microscopy showed a change in the intracellular membrane alterations from a clustered mitochondrial distribution with wild-type protein A to the formation of perinuclear layers with ER-targeted protein A. We conclude that specific intracellular membranes are not required for FHV RNA replication complex formation and function.
Sildenafil citrate (Viagra) enhances vasodilatation in fetal growth restriction.

BACKGROUND Fetal growth restriction (FGR) affects up to 8% of all pregnancies and has massive short-term (increased fetal morbidity and mortality) and long-term (increased incidence of cardiovascular disease in adulthood) health implications. Doppler waveform analysis of pregnancies complicated by FGR suggests compromised uteroplacental circulation and placental hypoperfusion. Our aim was to determine whether myometrial small artery function was aberrant in FGR and to assess whether sildenafil citrate could improve vasodilatation in FGR pregnancies. METHODS Small arteries dissected from myometrial biopsies obtained at cesarean section from normal pregnant women (n = 27) or women whose pregnancies were complicated by FGR (n = 12) were mounted on wire myographs. Vessels were constricted (with arginine vasopressin or U46619) and relaxed (with bradykinin) before and after incubation with a phosphodiesterase-5 inhibitor, sildenafil citrate. RESULTS We demonstrated increased myometrial small artery vasoconstriction and decreased endothelium-dependent vasodilatation in vessels from women whose pregnancies were complicated by FGR. Sildenafil citrate significantly reduced vasoconstriction and significantly improved relaxation of FGR small arteries. CONCLUSIONS We conclude that sildenafil citrate improves endothelial function of myometrial vessels from women whose pregnancies are complicated by intrauterine growth restriction. Sildenafil citrate may offer a potential therapeutic strategy to improve uteroplacental blood flow in FGR pregnancies.
Differential Expression of Interleukins (IL)‐13 and IL‐15 in Ectopic and Eutopic Endometrium of Women With Endometriosis and Normal Fertile Women

PROBLEM: Interleukins (IL) 13 and 15 are key regulators of inflammatory and immune responses, processes that are central to endometriosis and associated abnormalities. The present study examined (1) whether ectopic endometrial tissue expresses IL‐13 and IL‐15 (2) if their expression differs compared with matched eutopic endometrium and control endometrium from normal fertile women, and (3) if peritoneal fluids (PF) content of these cytokines reflects the disease compared with PF from women with peritoneal adhesions unrelated to endometriosis and those without pelvic pathology.