Miracle-dz/UniFAR-FTUs huggingface dataset:
Diversity of Vascular Reactivity and the Treatment Response in Diabetic, Hypertensive, Hyperlipidemic, and Healthy Rats Subjected to Hemorrhagic Shock

ABSTRACT The current diagnosis and treatment guidelines for severe trauma and shock are all for healthy population. Few studies focused on the pathophysiological features and treatments in metabolic diseases after severe trauma and shock. Vascular reactivity is significantly decreased after severe trauma and shock. Improving the vascular reactivity with arginine vasopressin (AVP) and phorbol-12 myristate-13-acetate (PMA) is beneficial to trauma and shock. Whether the cardiovascular function and treatment responses have the own features in hypertensive, diabetic, and hyperlipidemic patients after traumatic hemorrhagic shock is not known. Using hypertensive, diabetic, and hyperlipidemic and healthy rats, we compared the change patterns in cardiovascular function including vascular reactivity, tissue perfusion, and the hemodynamics after hemorrhagic shock and their responses to AVP, PMA, and common antishock agents including dopamine and norepinephrine. A same degree of hemorrhagic shock (40% hemorrhage or mean arterial pressure maintained at 40 mm Hg for 2 h) resulted in a more obvious decrease in vascular reactivity, hemodynamics, tissue perfusion, and mitochondrial function of liver and kidney in hypertensive, diabetic, and hyperlipidemic rats, and a more rapidly natural death than in healthy rats. The effectiveness of AVP and PMA in these diseased rats was lower than in healthy rats. The effective dosage of common antishock agents including norepinephrine, dopamine, and AVP in healthy rats was wider than that in these diseased rats. Among the antishock agents used in the current study, AVP had the best effect in improving animal survival and vascular reactivity both in healthy and in diseased rats. These findings suggest that hypertensive, diabetic, and hyperlipidemic rats have a worse vascular reactivity and organ function than the healthy rats after traumatic hemorrhagic shock, which result in the worse treatment responses and effects to vasoactive agents. Lower dose of AVP can be recommended as the first-line antishock agents for these diseased rats.
Evaluation of biomarkers for in vitro prediction of drug-induced nephrotoxicity: comparison of HK-2, immortalized human proximal tubule epithelial, and primary cultures of human proximal tubular cells

There has been intensive effort to identify in vivo biomarkers that can be used to monitor drug‐induced kidney damage and identify injury before significant impairment occurs. Kidney injury molecule‐1 (KIM‐1), neutrophil gelatinase‐associated lipocalin (NGAL), and human macrophage colony stimulating factor (M‐CSF) have been validated as urinary and plasma clinical biomarkers predictive of acute and chronic kidney injury and disease. Similar validation of a high throughput in vitro assay predictive of nephrotoxicity could potentially be implemented early in drug discovery lead optimization to reduce attrition at later stages of drug development. To assess these known in vivo biomarkers for their potential for in vitro screening of drug‐induced nephrotoxicity, we selected a panel of nephrotoxic agents and examined their effects on the overexpression of nephrotoxicity biomarkers in immortalized (HK‐2) and primary (commercially available and freshly in‐house produced) human renal proximal tubule epithelial cells. Traditional cytotoxicity was contrasted with expression levels of KIM‐1, NGAL, and M‐CSF assessed using ELISA and real‐time quantitative reverse transcription PCR. Traditional cytotoxicity assays and biomarker assays using HK‐2 cells were both unsuitable for prediction of nephrotoxicity. However, increases in protein levels of KIM‐1 and NGAL in primary cells were well correlated with dose levels of known nephrotoxic compounds, with limited correlation seen in M‐CSF protein and mRNA levels. These results suggest that profiling compounds against primary cells with monitoring of biomarker protein levels may have potential as in vitro predictive assays of drug‐induced nephrotoxicity.
The Kerr/CFT Correspondence and its Extensions

We present a first-principles derivation of the main results of the Kerr/CFT correspondence and its extensions using only tools from gravity and quantum field theory, filling a few gaps in the literature when necessary. Firstly, we review properties of extremal black holes that imply, according to semi-classical quantization rules, that their near-horizon quantum states form a centrally-extended representation of the one-dimensional conformal group. This motivates the conjecture that the extremal Kerr and Reissner-Nordström black holes are dual to the chiral limit of a two-dimensional CFT. We also motivate the existence of an SL(2, ℤ) family of two-dimensional CFTs, which describe in their chiral limit the extremal Kerr-Newman black hole. We present generalizations in anti-de Sitter spacetime and discuss other matter-coupling and higher-derivative corrections. Secondly, we show how a near-chiral limit of these CFTs reproduces the dynamics of near-superradiant probes around near-extremal black holes in the semi-classical limit. Thirdly, we review how the hidden conformal symmetries of asymptotically-flat black holes away from extremality, combined with their properties at extremality, allow for a microscopic accounting of the entropy of non-extremal asymptotically-flat rotating or charged black holes. We conclude with a list of open problems.
Marine sulfate-reducing bacteria cause serious corrosion of iron under electroconductive biogenic mineral crust

Iron (Fe0) corrosion in anoxic environments (e.g. inside pipelines), a process entailing considerable economic costs, is largely influenced by microorganisms, in particular sulfate-reducing bacteria (SRB). The process is characterized by formation of black crusts and metal pitting. The mechanism is usually explained by the corrosiveness of formed H2S, and scavenge of ‘cathodic’ H2 from chemical reaction of Fe0 with H2O. Here we studied peculiar marine SRB that grew lithotrophically with metallic iron as the only electron donor. They degraded up to 72% of iron coupons (10 mm × 10 mm × 1 mm) within five months, which is a technologically highly relevant corrosion rate (0.7 mm Fe0 year−1), while conventional H2-scavenging control strains were not corrosive. The black, hard mineral crust (FeS, FeCO3, Mg/CaCO3) deposited on the corroding metal exhibited electrical conductivity (50 S m−1). This was sufficient to explain the corrosion rate by electron flow from the metal (4Fe0 → 4Fe2+ + 8e−) through semiconductive sulfides to the crust-colonizing cells reducing sulfate (8e− + SO42− + 9H+ → HS− + 4H2O). Hence, anaerobic microbial iron corrosion obviously bypasses H2 rather than depends on it. SRB with such corrosive potential were revealed at naturally high numbers at a coastal marine sediment site. Iron coupons buried there were corroded and covered by the characteristic mineral crust. It is speculated that anaerobic biocorrosion is due to the promiscuous use of an ecophysiologically relevant catabolic trait for uptake of external electrons from abiotic or biotic sources in sediments.
Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation

ABSTRACT Despite a remarkable reduction in the past decades, cytomegalovirus (CMV) disease in allogeneic hematopoietic stem cell transplant (HSCT) recipients remains a feared complication, still associated with significant morbidity and mortality. Today, first line treatment of CMV infection/reactivation is still based on dated antiviral compounds Ganciclovir (GCV), Foscarnet (FOS) and Cidofovir (CDF) with their burdensome weight of side effects. Maribavir (MBV), Letermovir (LMV) and Brincidofovir (BDF) are three new promising anti-CMV drugs without myelosuppressive properties or renal toxic effects that are under investigation in randomized phase II and III trials. Adoptive T-cell therapy (ATCT) in CMV infection possesses a strong rationale, demonstrated by several proof of concept studies; its feasibility is currently under investigation by clinical trials. ATCT from third-party and naïve donors could meet the needs of HSCT recipients of seronegative donors and cord blood grafts. In selected patients such as recipients of T-cell depleted grafts, ATCT, based on CMV-specific host T-cells reconstitution kinetics, would be of value in the prophylactic and/or preemptive CMV treatment. Vaccine-immunotherapy has the difficult task to reduce the incidence of CMV reactivation/infection in highly immunocompromised HSCT patients. Newer notions on CMV biology may represent the base to flush out the Troll of transplantation.
DrugBank: a comprehensive resource for in silico drug discovery and exploration

DrugBank is a unique bioinformatics/cheminformatics resource that combines detailed drug (i.e. chemical) data with comprehensive drug target (i.e. protein) information. The database contains >4100 drug entries including >800 FDA approved small molecule and biotech drugs as well as >3200 experimental drugs. Additionally, >14,000 protein or drug target sequences are linked to these drug entries. Each DrugCard entry contains >80 data fields with half of the information being devoted to drug/chemical data and the other half devoted to drug target or protein data. Many data fields are hyperlinked to other databases (KEGG, PubChem, ChEBI, PDB, Swiss-Prot and GenBank) and a variety of structure viewing applets. The database is fully searchable supporting extensive text, sequence, chemical structure and relational query searches. Potential applications of DrugBank include in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical education. DrugBank is available at http://redpoll.pharmacy. ualberta.ca/drugbank/.
Modular snake robot gaits on horizontal pipes

In this paper, a comparative analysis of different gaits were done using modular snake robots. They move along different sizes of horizontal pipes. Pipe sizes were chosen according to robot's length. Gaits were chosen to match robot stability and effectiveness criteria on these surfaces. A description of gait design process is shown. Parametrized schemes were used to control the robot. A visualization tool was used to validate the gait designs prior their implementation on the real robot. Performance metrics, regarding robot's locomotion speed and energy efficiency were developed. A series of experiments were carried out to compare the performance of the selected gaits under these criteria. The experiments can be observed on the accompanying video. Among selected gaits, lateral rolling has demonstrated to be suitable for every pipe size. The fastest speed v = 46.5cm/s, and the most efficient locomotion, under the metrics proposed here, are also shown.
Post-operative radiochemotherapy in patients with gastric cancer: one department's experience of 56 patients.

OBJECTIVES Prognosis in patients with locally advanced stomach cancer undergoing surgery alone is poor. High local failure rates in gastric cancer have been reported of up to 70%. When a relapse occurs, attempts at curative treatment are generally unsuccessful. A retrospective analysis was performed in order to determine whether post-operative radiochemotherapy improves treatment results in patients with locally advanced gastric cancer. METHODS Between November 2004 and July 2008, 56 patients with clinical Stage IB-IV cancer of the stomach underwent curative gastrectomy and adjuvant radiochemotherapy. Patients with distant metastases were excluded from the analysis. The total radiation dose was 45.0 Gy. The chemotherapy regimen comprised a 5 day cycle of 5-fluorouracil at 425 mg m(-2) and leucovorin at 20 mg m(-2). Overall survival and disease-free survival, as well as toxicity, were estimated for all patients. RESULTS Within the study group there were 7 (13%) local recurrences, 4 (7%) distant metastases and 8 (14%) local and distant relapses. The 2 year overall survival was 48%. A total of 19 (34%) patients developed Grade 3 gastrointestinal toxicity. There were no treatment-related deaths. CONCLUSION Post-operative radiochemotherapy is an effective and safe regimen in patients with curatively resected locally advanced gastric cancer.
Suppression of Innate Immunity by Acute Ethanol Administration: A Global Perspective and a New Mechanism Beginning with Inhibition of Signaling through TLR31

Excessive consumption of ethanol (EtOH) suppresses innate immunity, but the mechanisms have not been fully delineated. The present study was conducted to determine whether EtOH suppresses TLR signaling in vivo in mice and to characterize the downstream effects of such suppression. Degradation of IL-1R-associated kinase 1 induced by a TLR3 ligand in peritoneal cells (∼90% macrophages) was suppressed by EtOH. Phosphorylation of p38 kinase in peritoneal macrophages (F4/80+) was suppressed, as was nuclear translocation of p-c-Jun and p65 in peritoneal cells. EtOH decreased IL-6 and IL-12 (p40), but did not significantly affect IL-10 in peritoneal lavage fluid or in lysates of peritoneal cells. Changes in cytokine mRNAs (by RNase protection assay) in macrophages isolated by cell sorting or using Ficoll were generally consistent with changes in protein levels in cell lysates and peritoneal lavage fluid. Thus, suppression of TLR signaling and cytokine mRNA occurred in the same cells, and this suppression generally corresponded to changes in i.p. and intracellular cytokine concentrations. DNA microarray analysis revealed the suppression of an IFN-related amplification loop in peritoneal macrophages, associated with decreased expression of numerous innate immune effector genes (including cytokines and a chemokine also suppressed at the protein level). These results indicate that EtOH suppresses innate immunity at least in part by suppressing TLR3 signaling, suppressing an IFN-related amplification loop, and suppressing the induction of a wide range of innate effector molecules in addition to proinflammatory cytokines and chemokines.
Evidence against a mean-field description of short-range spin glasses revealed through thermal boundary conditions

A theoretical description of the low-temperature phase of short-range spin glasses has remained elusive for decades. In particular, it is unclear if theories that assert a single pair of pure states, or theories that are based infinitely many pure states-such as replica symmetry breaking-best describe realistic short-range systems. To resolve this controversy, the three-dimensional Edwards-Anderson Ising spin glass in thermal boundary conditions is studied numerically using population annealing Monte Carlo. In thermal boundary conditions all eight combinations of periodic vs antiperiodic boundary conditions in the three spatial directions appear in the ensemble with their respective Boltzmann weights, thus minimizing finite-size corrections due to domain walls. From the relative weighting of the eight boundary conditions for each disorder instance a sample stiffness is defined, and its typical value is shown to grow with system size according to a stiffness exponent. An extrapolation to the large-system-size limit is in agreement with a description that supports the droplet picture and other theories that assert a single pair of pure states. The results are, however, incompatible with the mean-field replica symmetry breaking picture, thus highlighting the need to go beyond mean-field descriptions to accurately describe short-range spin-glass systems.
In Vivo Distribution of Human Adipose‐Derived Mesenchymal Stem Cells in Novel Xenotransplantation Models

The potential for human adipose‐derived mesenchymal stem cells (AMSC) to traffic into various tissue compartments was examined using three murine xenotransplantation models: nonobese diabetic/severe combined immunodeficient (NOD/SCID), nude/NOD/SCID, and NOD/SCID/MPSVII mice. Enhanced green fluorescent protein was introduced into purified AMSC via retroviral vectors to assist in identification of cells after transplantation. Transduced cells were administered to sublethally irradiated immune‐deficient mice through i.v. , intraperitoneal, or subcutaneous injection. Up to 75 days after transplantation, tissues were harvested and DNA polymerase chain reaction (PCR) was performed for specific vector sequences as well as for human Alu repeat sequences. Duplex quantitative PCR using human β‐globin and murine rapsyn primers assessed the contribution of human cells to each tissue. The use of the novel NOD/SCID/MPSVII mouse as a recipient allowed rapid identification of human cells in the murine tissues, using an enzyme reaction that was independent of surface protein expression or transduction with an exogenous transgene. For up to 75 days after transplantation, donor‐derived cells were observed in multiple tissues, consistently across the various administration routes and independent of transduction parameters. Tissue localization studies showed that the primary MSC did not proliferate extensively at the sites of lodgement. We conclude that human AMSC represent a population of stem cells with a ubiquitous pattern of tissue distribution after administration. AMSC are easily obtained and highly amenable to current transduction protocols for retroviral transduction, making them an excellent avenue for cell‐based therapies that involve a wide range of end tissue targets.
Direct Fuzzy Adaptive Control of a Manipulator with Elastic Joints

The use of harmonic drive gear boxes in space robotic applications offer several attractive properties, such as high reduction ratio, compact size, low mass, and coaxial assembly. However, the flexibility effects of this type of gear mechanism in the joints of robotic manipulators are significant enough to make real-time control challenging. This paper addresses the problem of fuzzy adaptive trajectory control of space manipulators that exhibit elastic vibrations in their joints and that are subject to parametric uncertainties and dynamics modeling errors. The developed control scheme uses a fuzzy adaptation mechanism that varies in real-time the gains of a slow control term designed to stabilize the rigid dynamics, and a linear correction term to further reduce the elastic vibrations at the joints. The proposed controller is validated in numerical simulations in a trajectory tracking scenario by a flexible-joint manipulator. Simulation results suggest that the controller is robust to uncertainties in joint stiffness coefficients and to modeling errors, and yields improved tracking performance compared with conventional flexible-joint control strategies.
Silver Binding Nucleolar Organizer Regions Dots in Oral Leukoplakia with Epithelial Dysplasia and Oral Squamous Cell Carcinoma: An In Vivo Study

Silver binding nucleolar organizer regions (AgNOR) in normal oral mucosa (NOM), oral leukoplakia with epithelial dysplasia (ED), and oral squamous cell carcinoma (OSCC) were studied. The mean AgNOR count per nucleus increased from NOM to ED to OSCC. Tissue showing ED in oral leukoplakia and OSCC cases showed higher counts, wider scatter, and smaller size of AgNOR dots in the nuclei. The study seems to suggest that time method has some potential in distinguishing between NOM and oral leukoplakia with ED and OSCC. Studies of larger numbers are needed to arrive at more substantial conclusions.
Reduction in extrapulmonary tuberculosis in context of antiretroviral therapy scale-up in rural South Africa

SUMMARY Scale-up of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection has reduced the incidence of pulmonary tuberculosis (PTB) in South Africa. Despite the strong association of HIV infection with extrapulmonary tuberculosis (EPTB), the effect of ART on the epidemiology of EPTB remains undocumented. We conducted a retrospective record review of patients initiated on treatment for EPTB in 2009 (ART coverage <5%) and 2013 (ART coverage 41%) at four public hospitals in rural Mopani District, South Africa. Data were obtained from TB registers and patients’ clinical records. There was a 13% decrease in overall number of TB cases, which was similar for cases registered as EPTB (n = 399 in 2009 vs. 336 in 2013; P < 0·01) and for PTB (1031 vs. 896; P < 0·01). Among EPTB cases, the proportion of miliary TB and disseminated TB decreased significantly (both P < 0·01), TB meningitis and TB of bones increased significantly (P < 0·01 and P = 0·02, respectively) and TB pleural effusion and lymphadenopathy remained the same. This study shows a reduction of EPTB cases that is similar to that of PTB in the context of the ART scale-up. The changing profile of EPTB warrants attention of healthcare workers.
Investigating a Liver Fat: Arterial Stiffening Pathway in Adult and Childhood Obesity.

OBJECTIVE To investigate the relationship between hepatic fat content, circulating triglyceride levels and aortic stiffness in adult and childhood obesity. APPROACH AND RESULTS Seventy-seven adults and 18 children across a wide range of body mass index (18.5-52.6 kg/m(2); percentile 8-100) with no identifiable cardiac risk factors underwent; 1H- magnetic resonance spectroscopy to quantify hepatic fat content and magnetic resonance imaging to assess aortic pulse wave velocity (PWV) and regional distensibility. In adults, multivariable regression showed age (β=0.09; P=0.02), liver fat (β=2.5; P=0.04), and serum triglyceride (β=0.47; P=0.01) to be independent predictors of PWV. Age and blood pressure-adjusted, moderated regression showed that 43% of the total negative effect of hepatic fat on PWV is attributable to indirect effects via increased triglyceride (P=0.005). In addition, regional distensibility was positively correlated with hepatic fat (ascending; r=-0.35; descending, r=-0.23; abdominal, r=-0.41; all P<0.001). Similar to that seen in adults, PWV (r=0.72; P<0.001) and abdominal regional distensibility (r=-0.52; P<0.001) were correlated with liver fat in children. CONCLUSIONS Increasing age, liver fat, and triglyceride are all related to increased aortic stiffness in adults. Even when controlling for the effects of age and blood pressure, hepatic fat has a negative effect on PWV, with substantial indirect effect occurring via increased circulating triglyceride level. This relationship between hepatic fat and aortic stiffness occurs early in the obesity process and is also seen in children. As such, hepatic fat content is a potential therapeutic target to treat the elevated vascular risk in obesity.
Age, Breed Designation, Coat Color, and Coat Pattern Influenced the Length of Stay of Cats at a No-Kill Shelter

Adoption records from the Tompkins County Society for the Prevention of Cruelty to Animals, an open-admission, no-kill shelter in New York State, were examined to determine if various physical attributes influenced the length of stay (LOS) of cats and kittens. Similar reports from other no-kill shelters have not been published. LOS averaged 61.2 days for cats and kittens combined and ranged from less than 1 day to 730 days. Based on mixed models that accounted for lack of independence among attributes, younger, lighter-colored cats were generally adopted more quickly than older, more darkly colored cats, but yellow-colored cats had the greatest LOS. Coat color did not influence LOS for kittens. Coat patterning and breed designation influenced LOS in both cats and kittens. Male cats and kittens had a shorter LOS than female cats and kittens, respectively. Studies from traditional shelters also demonstrated the importance of physical characteristics to adopters. Given adopter preferences for companion animals with certain characteristics, methods to reduce the LOS for cats with the longest potential residences at the shelter require continued development.