Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroanatomical correlates of voluntary inhibition of accommodation/vergence under monocular open‐loop viewing conditions

The purpose of this work is to identify human neural circuits involved in inhibition of accommodation/vergence by contrasting the cortical functions subservient to negative voluntary accommodation/vergence (NVA) with those evoked by active fixation in darkness (FIX). Five subjects with normal corrected acuity were studied using positron emission tomography and the HO bolus technique. The dominant right eye viewed a laser speckle pattern (633 nm) whose direction and velocity of motion were determined by the refractive state of the eye. The speckle pattern was presented at a distance of 1.8 m (0.55 D). The non‐dominant eye was patched. Subjects performed two tasks counterbalanced for order effects: (i) attempted fixation on the remembered target in darkness with the dominant eye open and ‘fixating’; and (ii) voluntary reduction of the laser speckle flow during each alternate 20‐s epoch when a convex +2.0 D lens was placed in front of the right eye causing the speckle pattern to move downwards at 3 °/s. Comparison of the condition of NVA with the condition of FIX indicated widespread occipital activation. Decreases in absolute regional cerebral blood flow occurred in the superior parietal cortex (BA 5), frontal cortex (BA 8 and 10) and within the postcentral/precentral gyrus (BA 1/2/3/4) bilaterally where deactivation clusters eclipsed the presumed neck and shoulder areas. Negative accommodation/vergence appears to be driven by a reduction of parasympathetic tone, and has the effect of shutting down brain regions known to be involved in regulating visual search as well as a centrally controlled eye–head–neck–shoulder motor programme responsible for posturing gaze.
Optimal therapy in genotype 4 chronic hepatitis C: finally cured?

Optimal therapy for patients with hepatitis C virus (HCV) genotype 4 (HCV‐4) infection is changing rapidly, and the possibility of a total cure is near. The standard of care has been combination pegylated interferon (PEG‐IFN)‐ribavirin (RBV), with modest response rates and considerable adverse events. Since the introduction of sofosbuvir (SOF), simeprevir (SIM), and daclatasvir (DCV), the duration of treatment has been significantly shortened and response rates have increased. The recommended treatment for IFN‐eligible patients is PEG‐IFN/RBV plus SOF, SIM or DCV. In IFN ineligible patients, the optimal regimen is a 24‐week course of SOF/RBV, or a 12‐week course of SOF‐SIM or SOF‐DCV with or without RBV. The pipeline for patients with chronic HCV is highly active. IFN‐free combinations with paritaprevir‐ombitasvir, SOF‐ledipasvir, or DCV‐asunaprevir (ASV)‐beclabuvir (BMS‐791325) for 12 weeks or less with close to 100% cure rates will soon become the optimal therapy.
RON Receptor Tyrosine Kinase, a Negative Regulator of Inflammation, Inhibits HIV-1 Transcription in Monocytes/Macrophages and Is Decreased in Brain Tissue from Patients with AIDS1

Activation of macrophages and microglia cells after HIV-1 infection and their production of inflammatory mediators contribute to HIV-associated CNS diseases. The mechanisms that initiate and maintain inflammation after HIV-1 infection in the brain have not been well studied. Furthermore, it is not understood why in HIV-associated CNS disease, macrophages and microglia are biased toward inflammation rather than production of mediators that control inflammation. We have focused on the receptor tyrosine kinase RON, a critical negative regulator of macrophage function and inflammation, to determine whether this receptor regulates HIV-1 expression. Overexpressing RON in monocytes/macrophages demonstrates that RON inhibits HIV-1 proviral transcription in part by decreasing the binding activity of NF-κB to the HIV-1 long terminal repeat. Because macrophages and microglia cells are a critical reservoir for HIV-1 in the CNS, we examined brain tissues for RON expression and detected RON in astrocytes, cortical neurons, and monocytoid cells. RON was detected in all control patients who were HIV seronegative (n = 7), whereas six of nine brain samples obtained from AIDS patients exhibited reduced RON protein. These data suggest that RON initiates signaling pathways that negatively regulate HIV-1 transcription in monocytes/macrophages and that HIV-1 suppresses RON function by decreasing protein levels in the brain to assure efficient replication. Furthermore, HIV-1 infection would compromise the ability of RON to protect against inflammation and consequent CNS damage.
Smoking and the long-term incidence of age-related macular degeneration: the Blue Mountains Eye Study.

OBJECTIVE To assess the association between smoking and long-term incident age-related macular degeneration (AMD). METHODS Of 3654 Australians 49 years and older examined at baseline (January 14, 1992, through December 18, 1993), 2454 were examined 5 years later (January 11, 1997, through February 23, 2000), 10 years later (July 10, 2002, through November 4, 2005), or both. Retinal photographs were taken to assess AMD. Smoking status was recorded at each interview. RESULTS After controlling for age, sex, and other factors, current smokers had a 4-fold higher risk of late AMD than never smokers (relative risk, 3.9; 95% confidence interval, 1.7-8.8). Past smokers had a 3-fold higher risk of geographic atrophy (relative risk, 3.4; 95% confidence interval, 1.2-9.7). Joint exposure to current smoking and (1) the lowest level of high-density lipoprotein (HDL) cholesterol, (2) the highest total to HDL cholesterol ratio, or (3) low fish consumption was associated with a higher risk of late AMD than the effect of any risk factor alone. However, interactions between smoking and HDL cholesterol level, ratio of total to HDL cholesterol, and fish consumption were not statistically significant. CONCLUSION Smoking strongly increased the long-term risk of incident late, but not early, AMD, with a possibly greater effect in persons with a low HDL cholesterol level, a high ratio of total to HDL cholesterol, and low fish consumption.
Development of Multivariable Models to Predict and Benchmark Transfusion in Elective Surgery Supporting Patient Blood Management

Summary Background: Blood transfusion is a highly prevalent procedure in hospitalized patients and in some clinical scenarios it has lifesaving potential. However, in most cases transfusion is administered to hemodynamically stable patients with no benefit, but increased odds of adverse patient outcomes and substantial direct and indirect cost. Therefore, the concept of Patient Blood Management has increasingly gained importance to pre-empt and reduce transfusion and to identify the optimal transfusion volume for an individual patient when transfusion is indicated. Objectives: It was our aim to describe, how predictive modeling and machine learning tools applied on pre-operative data can be used to predict the amount of red blood cells to be transfused during surgery and to prospectively optimize blood ordering schedules. In addition, the data derived from the predictive models should be used to benchmark different hospitals concerning their blood transfusion patterns. Methods: 6,530 case records obtained for elective surgeries from 16 centers taking part in two studies conducted in 2004–2005 and 2009–2010 were analyzed. Transfused red blood cell volume was predicted using random forests. Separate models were trained for overall data, for each center and for each of the two studies. Important characteristics of different models were compared with one another. Results: Our results indicate that predictive modeling applied prior surgery can predict the transfused volume of red blood cells more accurately (correlation coefficient cc = 0.61) than state of the art algorithms (cc = 0.39). We found significantly different patterns of feature importance a) in different hospitals and b) between study 1 and study 2. Conclusion: We conclude that predictive modeling can be used to benchmark the importance of different features on the models derived with data from different hospitals. This might help to optimize crucial processes in a specific hospital, even in other scenarios beyond Patient Blood Management. Citation: Hayn D, Kreiner K, Ebner H, Kastner P, Breznik N, Rzepka A, Hofmann A, Gombotz H, Schreier G. Development of multivariable models to predict and benchmark transfusion in elective surgery supporting patient blood management. Appl Clin Inform 2017; 8: 617–631 https://doi.org/10.4338/ACI-2016-11-RA-0195
Personality Disorder Assessments in Acute Depressive Episodes: Stability at Follow-Up

Abstract Assessment of personality disorders during the acute phase of major depression may be invalidated by the potential distortion of personality traits in depressed mood states. However, few studies have tested this assumption. We examined the stability of personality disorder diagnoses during and then after a major depressive episode (MDE). Subjects with major depression (N = 82) completed the 17-item Hamilton Depression Scale (HAM-17) and the Structured Clinical Interview for Axis II both at baseline during an MDE and at 3-month follow-up. We compared subjects who continued to meet DSM-IV criteria for the same Axis II diagnoses with patients whose diagnosis changed and patients with no DSM-IV personality disorder to determine the relationship to major depression and its severity. Sixty-six percent of subjects met DSM-IV criteria for at least one Axis II diagnosis at baseline and 80% had the same personality disorder diagnoses at follow-up. Thirty-four percent had a full remission of MDE at 3-month follow-up. Instability of Axis II diagnosis was associated with number of Axis II diagnoses at baseline (p = .036) and Hispanic ethnicity (p = .013). HAM-17 score change was unrelated to differences in the number of symptoms of personality disorders from baseline to follow-up, nor was remission from MDE on follow-up. Axis II diagnoses in acutely depressed patients reassessed after 3 months are often stable and not associated with remission of or improvement in major depression.
Restrictive fluid resuscitation in combination with damage control resuscitation: Time for adaptation

BACKGROUND Damage control resuscitation (DCR) conveys a survival advantage in patients with severe hemorrhage. The role of restrictive fluid resuscitation (RFR) when used in combination with DCR has not been elucidated. We hypothesize that RFR, when used with DCR, conveys an overall survival benefit for patients with severe hemorrhage. METHODS This is a retrospective analysis from January 2007 to May 2011 at a Level I trauma center. Inclusion criteria included penetrating torso injuries, systolic blood pressure less than or equal to 90 mm Hg, and managed with DCR and damage control surgery (DCS). There were two groups according to the quantity of fluid before DCS: (1) standard fluid resuscitation (SFR) greater than or equal to 150 mL of crystalloid; (2) RFR less than 150 mL of crystalloid. Demographics and outcomes were analyzed. RESULTS Three hundred seven patients were included. Before DCS, 132 (43%) received less than 150 mL of crystalloids, grouped under RFR; and 175 (57%) received greater than or equal to 150 mL of crystalloids, grouped under SFR. Demographics and initial clinical characteristics were similar between the study groups. Compared with the SFR group, RFR patients received less fluid preoperatively (129 mL vs. 2,757 mL; p < 0.001), exhibited a lower intraoperative mortality (9% vs. 32%; p < 0.001), and had a shorter hospital length of stay (13 vs. 18 days; p = 0.02). Patients in the SFR group had a lower trauma intensive care unit mortality (5 vs. 12%; p = 0.03) but exhibited a higher overall mortality. Patients receiving RFR demonstrated a survival benefit, with an odds ratio for mortality of 0.69 (95% confidence interval, 0.37–0.91). CONCLUSION To the best of our knowledge, this is the first civilian study that analyzes the impact of RFR in patients managed with DCR. Its use in conjunction with DCR for hypotensive trauma patients with penetrating injuries to the torso conveys an overall and early intraoperative survival benefit. LEVEL OF EVIDENCE Therapeutic study, level IV.
S‐adenosyl‐l‐methionine: transcellular transport and uptake by Caco‐2 cells and hepatocytes

S‐adenosyl‐l‐methionine (SAMe) is an endogenous molecule that is known to be protective against hepatotoxic injury. Although oral SAMe appears to be absorbed across the intestinal mucosa, its systemic bioavailability is low. The reason for this is unknown. Using the Caco‐2 cell culture model for enterocyte absorption, we determined the mode by which SAMe is transported across this cell monolayer. We also determined the extent it is taken up by both Caco‐2 cells and hepatocytes. In Caco‐2 cells transport was observed in both apical to basolateral and basolateral to apical directions. The apparent permeability coefficients (Papp) appeared to be concentration independent and were similar in both directions (0.7 times 10−6 and 0.6 times 10−6 cms−1, respectively), i.e. identical to that of the paracellular transport marker mannitol (0.9 times 10−6 and 0.7 times 10−6 cms−1). This mode of transport was supported by a four‐fold increase in the Papp for SAMe transport in Ca++‐free buffer. Cellular uptake of SAMe was examined in both Caco‐2 cells and cultured rat hepatocytes. Uptake by hepatocytes was not saturable in a concentration range of 0.001–100 μm. Accumulation by both cell types was very low, with a cell:medium ratio at equilibrium of only 0.2–0.5. This low cell accumulation supports the finding of paracellular transport as the only mode of cell membrane transport. Increased hepatocellular protection for SAMe may be accomplished by converting SAMe to a more lipid‐soluble prodrug.
Computational Electrocardiography: Revisiting Holter ECG Monitoring

Summary Background: Since 1942, when Goldberger introduced the 12-lead electrocardiography (ECG), this diagnostic method has not been changed. Objectives: After 70 years of technologic developments, we revisit Holter ECG from recording to understanding. Methods: A fundamental change is foreseen towards “computational ECG” (CECG), where continuous monitoring is producing big data volumes that are impossible to be inspected conventionally but require efficient computational methods. We draw parallels between CECG and computational biology, in particular with respect to computed tomography, computed radiology, and computed photography. From that, we identify technology and methodology needed for CECG. Results: Real-time transfer of raw data into meaningful parameters that are tracked over time will allow prediction of serious events, such as sudden cardiac death. Evolved from Holter’s technology, portable smartphones with Bluetooth-connected textile-embedded sensors will capture noisy raw data (recording), process meaningful parameters over time (analysis), and transfer them to cloud services for sharing (handling), predicting serious events, and alarming (understanding). To make this happen, the following fields need more research: i) signal processing, ii) cycle decomposition; iii) cycle normalization, iv) cycle modeling, v) clinical param -eter computation, vi) physiological modeling, and vii) event prediction. Conclusions: We shall start immediately developing methodology for CECG analysis and understanding.
Fenofibrate attenuates diabetic nephropathy in experimental diabetic rat's model via suppression of augmented TGF-β1/Smad3 signaling pathway

Abstract Context: Fibrates, the ligands of peroxisome profileferator-activated receptor-α have been shown to have a renal protective action in diabetic nephropathy (DN). Objective: This study aimed to elucidate the effect of fenofibrate on renal transforming growth factor-β1 (TGF-β1) and Smad3 in Streptozotocin (STZ)-induced DN. Methods: Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (55 mg/kg). Diabetic rats were given fenofibrate (100 mg/kg, p.o.). After 12 weeks, diabetic nephropathy biomarkers were assessed. The mRNA expression of collage I and III, TGF-β1 and Smad3 and were detected by RT–PCR. Results: Fenofibrate reduced significantly serum creatinine, kidney/body weight ratio, serum albumin excretion Collage I & III, TGF-β1 and Smad3 mRNA expression. Conclusions: Our results give further insights into the mechanisms underlying the protective role of fenofibrate in DN, suggesting that interference with TGF-β1/Smad3 signaling pathway may be a useful therapeutic approach to prevent DN.
Sulfhydryl Drug‐induced Eruption: A Clinical and Histological Study

Sulfhydryl drug‐induced skin eruptions were studied clinically and histologically in 23 patients. In this study, tiopronin, D‐penicillamine, captopril and gold sodium thiomalate were considered to be sulfhydryl drugs, because they have a thiol group or release sulfhydryl compounds. The clinical features included skin eruptions that were maculopapular, erythema mutiforme‐like, eczematous, psoriasis‐like, seborrheic dermatitis‐like, Gibert‐like, lichen planus‐like, and pemphigus‐like. These clinical findings were reminiscent of the wide variety of eruptions seen in cutaneous graft‐versus‐host reactions (GVHR). Histologically, areas of vacuolation and eosinophilic necrosis with a satellite infiltrate of lymphoid cells were seen in the epidermis, and perivascular infiltrates were noted in the dermis. These findings were similar to the histological picture of cutaneous GVHR. In skin tests with sulfhydryl compounds, 19 out of 20 subjects showed positive reactions, and autoantibodies were found in 8 out of 12 subjects tested.
Different Efficiency of Heat Shock Proteins (HSP) to Activate Human Monocytes and Dendritic Cells: Superiority of HSP601

One essential immunoregulatory function of heat shock protein (HSP) is activation of the innate immune system. We investigated the activation of human monocytes and monocyte-derived dendritic cells (DC) by recombinant human HSP60, human inducible HSP72, and preparations of human gp96 and HSP70 under stringent conditions, in the absence of serum and with highly purified monocytes. HSP60 induced human DC maturation and activated human DC to secrete proinflammatory cytokines. HSP72 induced DC maturation to a lesser extent, but activated human monocytes and immature DC as efficiently as HSP60 to release proinflammatory cytokines. The independence of the effects of HSP60 and HSP72 from endotoxin or another copurifying bacterial component was shown by the resistance of these effects to polymyxin B, their sensitivity to heat treatment, the inactivity of endotoxin controls at concentrations up to 100-fold above the endotoxin contents of the HSP, and the inactivity of a recombinant control protein. Preparations of HSP70, which consisted mainly of the constitutively expressed HSP73, induced only marginal cytokine release from monocytes. The gp96 preparations did not have significant effects on human monocytes and monocyte-derived DC, indicating that these human APC populations were not susceptible to gp96 signaling under the stringent conditions applied in this study. The biological activities of gp96 and HSP70 preparations were confirmed by their peptide binding activity. These findings show that HSP can differ considerably in the capacity to activate monocyte-derived APC under certain conditions and underline the potential of HSP60 and HSP72 as activation signals for the innate immune system.
Autonomy of Public Service Delivery Units in Vietnam: An Institutional Perspective

Intrigued by the burgeoning commercialisation of public services in Vietnam, this research seeks to understand the nature of autonomy that public service delivery units have been given as part of the greater effort of the Government of Vietnam to separate business and service provision from state management. In addressing this objective, the research bases its analysis on historical institutionalism and sociological institutionalism that illuminate insights into institutional factors shaping the autonomy policies and the implementation of the policies in practice. The main data sources the research draws on are legal documents, government reports and in-depth interviews with managers and staff of public service delivery units. The research findings illustrate that autonomy is very limited in many aspects of management because the autonomy reforms are largely influenced by the socialist-oriented market path dependence. Amidst the exhaustion of resources and legitimacy due to the regime’s flawed economic structure and inherent problems of cronyism and corruption, autonomy is utilized primarily as a strategic instrument to mobilize resources indispensable for the socialist survival. This policy direction creates incentives for the various forms of rent-seeking and corrupt behaviour among public service delivery units, occasioning the rapid and aggressive commercialization of public services. While the root of these problems lies in the intent of the policies, these problems are further nurtured by historical and cultural factors, and seriously compounded by the absence of an effective regulatory and accountability system and the lack of political commitment to fight corruption from the top leaders. The research addresses the gap in the academic literature by offering an illuminating insight into the nature of autonomy of a country context and demonstrating the merit of converging historical institutionalism and sociological institutionalism for the study of public policies. The research’s significant contribution to policy-making is that it highlights the need to build institutions to fit in well with the reform ideas, especially when such ideas are borrowed or transferred from advanced countries with well-developed institutional foundations.
Divergent natural selection with gene flow along major environmental gradients in Amazonia: insights from genome scans, population genetics and phylogeography of the characin fish Triportheus albus

The unparalleled diversity of tropical ecosystems like the Amazon Basin has been traditionally explained using spatial models within the context of climatic and geological history. Yet, it is adaptive genetic diversity that defines how species evolve and interact within an ecosystem. Here, we combine genome scans, population genetics and sequence‐based phylogeographic analyses to examine spatial and ecological arrangements of selected and neutrally evolving regions of the genome of an Amazonian fish, Triportheus albus. Using a sampling design encompassing five major Amazonian rivers, three hydrochemical settings, 352 nuclear markers and two mitochondrial DNA genes, we assess the influence of environmental gradients as biodiversity drivers in Amazonia. We identify strong divergent natural selection with gene flow and isolation by environment across craton (black and clear colour)‐ and Andean (white colour)‐derived water types. Furthermore, we find that heightened selection and population genetic structure present at the interface of these water types appears more powerful in generating diversity than the spatial arrangement of river systems and vicariant biogeographic history. The results from our study challenge assumptions about the origin and distribution of adaptive and neutral genetic diversity in tropical ecosystems. In addition, they have important implications for measures of biodiversity and evolutionary potential in one of the world’s most diverse and iconic ecosystems.