Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure-based ligand discovery for the Large-neutral Amino Acid Transporter 1, LAT-1

The Large-neutral Amino Acid Transporter 1 (LAT-1)—a sodium-independent exchanger of amino acids, thyroid hormones, and prescription drugs—is highly expressed in the blood–brain barrier and various types of cancer. LAT-1 plays an important role in cancer development as well as in mediating drug and nutrient delivery across the blood–brain barrier, making it a key drug target. Here, we identify four LAT-1 ligands, including one chemically novel substrate, by comparative modeling, virtual screening, and experimental validation. These results may rationalize the enhanced brain permeability of two drugs, including the anticancer agent acivicin. Finally, two of our hits inhibited proliferation of a cancer cell line by distinct mechanisms, providing useful chemical tools to characterize the role of LAT-1 in cancer metabolism.
Threshold of subjective auditory handicap.

A study of the hearing levels of a random sample of the rural population of the UK indicated that the threshold of subjective auditory handicap was age dependent and couldbe given by the expression log10 y = 0.0185x + 0.145, where y is hearing level in dB ISO (average of the values at 500, 1000 and 2000 Hz) corresponding to threshold of subjective auditory handicap and x is age in years of subject.
Forensic anthropology population data Facial soft tissue thickness of Brazilian adults

The auxiliary technique known as Facial Reconstruction enables one to reestablish the contours of the soft tissues over the skull, therefore producing a face and increasing the probability of a facial recognition. The reliability of this technique depends on the evaluation of the mean values of soft tissue thicknesses observed in a given population. Measurements were evaluated in autopsied corpses in ‘‘Section of Technical Verification of Deaths’’ in Guarulhos, São Paulo, Brazil. Thickness was measured manually by puncturing 10 midline craniometrical points and 11 bilateral points on a sample of 40 corpses of both sexes aged between 17 and 90 years, classified by skin color and the nutritional state. The results for the average thickness values are higher for males, variations related to the nutritional state are proportional to the increased fat on the face and age was not significant. The ethnic variable related to skin color when compared to studies with other populations showed differences, with the need for a reference table for a given population application of Facial Reconstruction technique in skulls of nonattributable identity. 2009 Elsevier Ireland Ltd. All rights reserved.
On the Factorization of Rational Discrete-Time Spectral Densities

In this paper, we consider an arbitrary matrix-valued, rational spectral density Φ(z). We show with a constructive proof that Φ(z) admits a factorization of the form Φ(z)=WT(z-1) W(z), where W(z) is stochastically minimal. Moreover, W(z) and its right inverse are analytic in regions that may be selected with the only constraint that they satisfy some symplectic-type conditions. By suitably selecting the analyticity regions, this extremely general result particularizes into a corollary that may be viewed as the discrete-time counterpart of the matrix factorization method devised by Youla in his celebrated work [48].
The Origin of the Variola Virus

The question of the origin of smallpox, one of the major menaces to humankind, is a constant concern for the scientific community. Smallpox is caused by the agent referred to as the variola virus (VARV), which belongs to the genus Orthopoxvirus. In the last century, smallpox was declared eradicated from the human community; however, the mechanisms responsible for the emergence of new dangerous pathogens have yet to be unraveled. Evolutionary analyses of the molecular biological genomic data of various orthopoxviruses, involving a wide range of epidemiological and historical information about smallpox, have made it possible to date the emergence of VARV. Comparisons of the VARV genome to the genomes of the most closely related orthopoxviruses and the examination of the distribution their natural hosts’ ranges suggest that VARV emerged 3000 to 4000 years ago in the east of the African continent. The VARV evolution rate has been estimated to be approximately 2 × 10−6 substitutions/site/year for the central conserved genomic region and 4 × 10−6 substitutions/site/year for the synonymous substitutions in the genome. Presumably, the introduction of camels to Africa and the concurrent changes to the climate were the particular factors that triggered the divergent evolution of a cowpox-like ancestral virus and thereby led to the emergence of VARV.
Monoclonal antibodies inhibiting IL-12, -23, and -17 for the treatment of psoriasis

ABSTRACT Psoriasis is a chronic, inflammatory, immune-mediated skin condition that affects 3 to 4% of the adult US population, characterized by well-demarcated, erythematous plaques with silver scale. Psoriasis is associated with many comorbidities including cardiometabolic disease and can have a negative impact on quality of life. The current armamentarium of psoriasis treatment includes topical therapies, phototherapy, oral immunosuppressive therapies, and biologic agents. Over the past 2 decades, there has been rapid development of novel biologic therapies for the treatment of moderate-to-severe plaque psoriasis. This article will review the role of IL-12, IL-23, and IL-17 in the pathogenesis of psoriasis and the monoclonal antibodies (ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, and risankizumab) that target these cytokines in the treatment of this disease.
A Synchronous Current Control Scheme for Multiphase Induction Motor Drives

Rotor-flux-oriented control of multiphase induction machines with sinusoidal magnetomotive force (MMF) distribution can be realized theoretically by using only two current controllers in the synchronous reference frame. In practice, however, this is inadequate, as shown in this paper using experimental results collected from five-phase induction motor drive laboratory prototypes. Various asymmetries of the machine and nonideal nature of the inverter necessitate an appropriate modification of the current control scheme in the rotating reference frame. Such a modified current control scheme is developed in this paper, and its ability to provide operation of the machine with a practically perfectly sinusoidal and balanced system of five-phase currents is demonstrated experimentally.
THE USE OF FDTD IN ESTABLISHING IN VITRO EXPERIMENTATION CONDITIONS REPRESENTATIVE OF LIFELIKE CELL PHONE RADIATION ON THE SPERMATOZOA

Recent studies have shown that exposing human semen samples to cell phone radiation leads to a significant decline in sperm parameters. In daily living, a cell phone is usually kept in proximity to the groin, such as in a trouser pocket, separated from the testes by multiple layers of tissue. The aim of this study was to calculate the distance between cell phone and semen sample to set up an in vitro experiment that can mimic real life conditions (cell phone in trouser pocket separated by multiple tissue layers). For this reason, a computational model of scrotal tissues was designed by considering these separating layers, the results of which were used in a series of simulations using the Finite Difference Time Domain (FDTD) method. To provide an equivalent effect of multiple tissue layers, these results showed that the distance between a cell phone and semen sample should be 0.8 cm to 1.8 cm greater than the anticipated distance between a cell phone and the testes.
The Influence of Endotoxemia on the Electroencephalographic and Antinociceptive Effects of Isoflurane in a Swine Model

BACKGROUND: We have previously reported that hemorrhagic shock decreases the minimum alveolar anesthetic concentration (MAC) of isoflurane but minimally alters the electroencephalographic (EEG) effect. In this study, we investigated the influence of endotoxemia on the EEG effect and the MAC of isoflurane. METHODS: Eighteen swine (25.7 ± 2.3 kg) were anesthetized by inhalation of isoflurane. The inhaled concentration was decreased to 0.5% and maintained for 20 min, before being returned to 2% and maintained for a further 20 min. End-tidal isoflurane concentrations and spectral edge frequencies were recorded. Analysis of the pharmacodynamics was performed using a sigmoidal inhibitory maximal effect model for spectral edge frequencies versus effect-site concentration. After measurement of the EEG effect, MAC was determined using the dewclaw clamp technique in which movement in response to clamping is recorded. After completion of control measurements, infusion of lipopolysaccharide (LPS, 1 &mgr;g · kg−1 · h−1) was started after a 100-&mgr;g bolus administration. After 1 h, the inhaled concentration of isoflurane was varied as in the control period, and the MAC was assessed again (LPS1h). The same procedures were also performed after 3 h of LPS infusion (LPS3h). RESULTS: Endotoxemia decreased the effect-site concentration that produced 50% of the maximal effect from 1.31% ± 0.22% to 1.13% ± 0.14% (LPS1h) and 1.03% ± 0.22% (LPS3h) and decreased the MAC from 2.05% ± 0.20% to 1.51% ± 0.30% (LPS1h) and 1.21% ± 0.29% (LPS3h). CONCLUSIONS: Endotoxemia increases both the hypnotic and antinociceptive effects of isoflurane, in contrast to hemorrhagic shock, and the extent of these alterations increases with progression of endotoxemia.
Tissue factor pathway inhibitor: structure, biology and involvement in disease

Tissue factor (TF)‐initiated coagulation plays a significant role in the pathophysiology of many diseases, including cancer and inflammation. Tissue factor pathway inhibitor (TFPI) is a plasma Kunitz‐type serine protease inhibitor, which modulates initiations of coagulation induced by TF. In a factor (F) Xa‐dependent feedback system, TFPI binds directly and inhibits the TF–FVII/FVIIa complex. Normally, TFPI exists in plasma both as a full‐length molecule and as variably carboxy‐terminal truncated forms. TFPI also circulates in complex with plasma lipoproteins. The levels and the dual inhibitor effect of TFPI on FXa and TF–FVII/FVIIa complex offers insight into the mechanisms of various pathological conditions triggered by TF. The use of selective pharmacological inhibitors has become an indispensable tool in experimental haemostasis and thrombosis research. In vivo administration of recombinant TFPI (rTFPI) in an experimental animal model prevents thrombosis (and re‐thrombosis after thrombolysis), reduces mortality from E. coli‐induced‐septic shock, prevents fibrin deposition on subendothelial human matrix and protects against disseminated intravascular coagulation (DIC). Thus, TFPI may play an important role in modulating TF‐induced thrombogenesis and it may also provide a unique therapeutic approach for prophylaxis and/or treatment of various diseases. In this review, we consider structural and biochemical aspects of the TFPI molecule and detail its inhibitory mechanisms and therapeutic implications in various disease conditions. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Sympathetic activation during early pregnancy in humans

• Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. • Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. • We found that vasomotor sympathetic activity was markedly greater, diastolic pressure trended lower, total peripheral resistance decreased, sympathetic vascular transduction was blunted, and renin and aldosterone both were higher during early pregnancy (i.e. ≤8 weeks of gestation) than pre‐pregnancy. • It is suggested that sympathetic activation is a common characteristic of early pregnancy in normotensive women. • These results help us better understand blood pressure control mechanisms during normal pregnancy in humans.
Small leucine rich repeat proteoglycans (SLRPs) in the human sclera: identification of abundant levels of PRELP.

PURPOSE The small leucine rich proteoglycan (SLRP) family is made up of several members which are thought to guide matrix assembly and organization through protein:protein and/or protein:carbohydrate interactions. In order to better characterize the composition of the scleral extracellular matrix, gene and protein expression of several members of the SLRP family were evaluated in the human sclera from donors aged 2-93 years of age. METHODS Semi-quantitative and quantitative RT-PCR analyses were performed on RNA isolated from human donor sclera using primers for decorin, fibromodulin, PRELP (proline arginine rich end leucine-rich protein), biglycan, chondroadherin, and lumican. Additionally, the protein expression and distribution of the SLRP family member, PRELP, was determined in the human sclera through western blot detection and immunohistochemistry. RESULTS Semi-quantitative and quantitative PCR analysis showed that all six SLRPs were expressed in the human sclera, with PRELP exhibiting the highest steady state mRNA levels, relative to that of the other SLRPs (p<0.001, ANOVA). Further analysis of PRELP in the human sclera by western blot analysis indicated that PRELP contained a 45 kDa core protein with short unsulfated keratan sulfate side chains and appeared in greatest abundance in sclera during the fourth decade of life. CONCLUSIONS These results suggest that several SLRP proteoglycans are expressed in the human sclera and provide the first description of the PRELP protein in the human sclera. The relative abundance of PRELP mRNA and protein in the human sclera, and the observed age-related variation in scleral PRELP expression suggests that PRELP may play a critical role in regulating the biomechanical properties of scleral extracellular matrix.
AUTOMATED DIFFERENTIAL LEUCOCYTE COUNTING: THE PRESENT STATE OF THE ART

It has been estimated (Ingrain & Preston, 1970) that ovcr oiic inillion differential lcucocytc counts (DLCs) are carried out daily in the United States. Besides being laborious and time consuming, the Ioo-cell DLC as carried out in most laboratories on a ‘wedge’ blood film is grossly inaccurate. The error of the DLC has been widely reviewed (England & Bain, 1976) and may be subdivided into three components, namely distributional errors resulting from the film preparation technique, statistical errors, which are a function of the number of cclls counted, and observer variability. It is therefore to be hoped that automation, besides eliminating a tedious chore, might also improve the accuracy and precision of the data obtained.
The co-ordinated cytokine/hormone response to acute injury incorporates leptin.

Recent studies have implicated leptin as a "stress" hormone and highlighted its association with increases in inflammatory cytokines, C-reactive protein and cortisol. In order to investigate the exact temporal leptin response to stress we undertook a detailed longitudinal study of circulating leptin concentrations during the well defined surgical injury of cholecystectomy. Circulating concentrations of cortisol, free fatty acids, leptin and C-reactive protein were measured at 3, 6, 9, 12, 18, 24, 48 and 72 h from the start of surgery in nine patients. There was a significant correlation between baseline concentrations of leptin and BMI (r=0. 893, P<0.001). Over the 72 h from the start of surgery there were significant (P<0.05) increases in the concentrations of all analytes (peak median concentrations); cortisol (6 h), free fatty acids (9 h), leptin (18 h) and C-reactive protein (48 h). Interestingly the timing of the leptin peak at approximately 18 h after an acute inflammatory stimulus is exactly the same as previously reported for interleukin 6. These data support the suggestion that the relationship between cortisol and leptin mirrors that of cortisol and another cytokine, interleukin 6, i.e. stimulatory in acute and suppressive in chronic situations. They also imply a physiological role for leptin in acute injury.
Self-compassion and social anxiety disorder

Abstract Self-compassion refers to having an accepting and caring orientation towards oneself. Although self-compassion has been studied primarily in healthy populations, one particularly compelling clinical context in which to examine self-compassion is social anxiety disorder (SAD). SAD is characterized by high levels of negative self-criticism as well as an abiding concern about others’ evaluation of one's performance. In the present study, we tested the hypotheses that: (1) people with SAD would demonstrate less self-compassion than healthy controls (HCs), (2) self-compassion would relate to severity of social anxiety and fear of evaluation among people with SAD, and (3) age would be negatively correlated with self-compassion for people with SAD, but not for HC. As expected, people with SAD reported less self-compassion than HCs on the Self-Compassion Scale and its subscales. Within the SAD group, lesser self-compassion was not generally associated with severity of social anxiety, but it was associated with greater fear of both negative and positive evaluation. Age was negatively correlated with self-compassion for people with SAD, whereas age was positively correlated with self-compassion for HC. These findings suggest that self-compassion may be a particularly important target for assessment and treatment in persons with SAD.
Jordanian Intensive Care Unit Nurses' Knowledge of Delirium Recognition.

INTRODUCTION Delirium is a clinical syndrome that negatively affects the outcomes of the intensive care units patients if undetected early and treated well. However, this condition remains under recognized and poorly managed by health care providers including nurses. The objective of this study was to check nurses' knowledge level about delirium recognition. MATERIALS & METHODS This was a cross-sectional study on 176 intensive care units nurses working in four major hospitals in Amman, Jordan. Data were collected using a self-reported likert scale questionnaire. RESULTS Nurses lack the basic knowledge about delirium recognition; the mean was (52.65 ± 4.99). Older nurses (aged 31 years and above) have significantly higher levels of knowledge regarding delirium recognition compared to younger nurses (mean ± SD, 56.02 ± 18.1 vs. 49.28 ± 12.65, P < .005). Moreover, nurses with longer experience in intensive care units were more knowledgeable about delirium recognition (r=0.73, p <.001). Graduate studies have a positive effect on the knowledge level. Nurses holding master degree have significantly higher levels of knowledge regarding delirium recognition compared to those with Baccalaureate degree; (mean ± SD, 60.28 ± 16.86 vs. 53.0 ± 12.18, P < .005). CONCLUSION Delirium is a widespread disorder in the intensive care units. Jordanian nurses lack the basic knowledge regarding essential characteristics of delirium and its recognition. Education of nurses in all care settings is vital and necessary.
Prevalence and Predictors of Nonadherence to Hemodialysis

Background: The prevalence of nonadherence to dialysis (NAD) presents a wide variation, depending on the parameters used and demographic regions studied. This study aimed to assess the prevalence and predictors of NAD of patients with chronic kidney disease undergoing hemodialysis (HD). Materials and Methods: This was a cross-sectional study with 255 adult patients receiving HD for >3 months. Skipping a session per month, shortening a session for at least 10 min, phosphorus >7.5 mg/dl, potassium >6.0 mmol/l and interdialytic weight gain (IDWG) >5.7% of body weight were indicative of NAD. The association of sociodemographic and clinical variables with NAD was assessed using logistic regression. Results: Mean age was 50 ± 13.1 years, 62.7% were male, 85.5% were of African descent and 62% were married. The prevalence rates of NAD were: 49% of shortening sessions, 18% of hyperkalemia, 12% of hyperphosphatemia, 9% of IDWG >5.7% of dry weight and 8% of skipping HD. Independent predictors of NAD were: age ≤50 years, not being married, living alone, living in Salvador, attending dialysis without a companion, ethnic African descent, Kt/V <1.3 and residual diuresis <100 ml/day. Conclusion: NAD is frequent and distinct sociodemographic and clinical variables predict different parameters.
Equity, Bonds, and Bank Debt: Capital Structure and Financial Market Equilibrium under Asymmetric Information

This paper proposes a model of financial markets and corporate finance, with asymmetric information and no taxes, where equity issues, bank debt, and bond financing coexist in equilibrium. The relationship banking aspect of financial intermediation is emphasized: firms turn to banks as a source of investment mainly because banks are good at helping them through times of financial distress. This financial flexibility is costly since banks face costs of capital themselves (which they attempt to minimize through securitization). To avoid this intermediation cost, firms may turn to bond or equity financing, but bonds imply an inefficient liquidation cost and equity an informational dilution cost. We show that in equilib‐rium the riskier firms prefer bank loans, the safer ones tap the bond markets, and the ones in between prefer to issue both equity and bonds. This segmentation is broadly consistent with stylized facts.
Life satisfaction and trauma in clinical and non-clinical children living in a war-torn environment: A discriminant analysis

The aim of this work was to discriminate between healthy children and children at risk of developing mental impairments by evaluating the impact on contextual and individual factors of a context characterized by war. We tested the hypothesis that a linear discriminant function composed of trauma, life satisfaction, and affect balance has the power to classify the children as community or clinical referred. Membership of the clinical-referred group was associated with poorer life satisfaction and higher levels of trauma. Community-referred profiles were associated with lesser trauma. Perceived life satisfaction regarding family and school was the main contributor to the discriminant function.
Andersen-Tawil syndrome, scarier for the doctor than for the patient? Who, when, and how to treat.

This editorial refers to ‘Cardiac characteristics and long-term outcome in Andersen–Tawil syndrome patients related to KCNJ2 mutation’ by E. Delannoy et al . , on page 1805. Andersen–Tawil syndrome (ATS) is a rare arrhythmia disorder combining a signature arrhythmia phenotype, consisting of a pronounced U-wave and frequent ventricular extrasystoles ( Figure 1 ) with extracardiac features including periodic paralysis and dysmorphic features.1 Occasionally, complex ventricular arrhythmias including bidirectional ventricular tachycardia and ventricular fibrillation occur.1 The pronounced U-wave can easily be distinguished from the ST segment, and because the QT interval itself is actually not prolonged,2,3 the generally used synonym long-QT syndrome type 7 seems inappropriate.2 Instead, ATS should probably be used, and because of the presumed heterogenetic basis, ATS type 1 is the appropriate terminology for at least half the cases in whom mutations are found in the KCNJ2 gene which encodes for the inward rectifying potassium channel Kir2.1 (conducting the inward rectifying potassium current I K1). 4 Other causal genes are likely to be present but have not been identified yet. Figure 1 Typical ECG of an ATS1 patient. Please note the large U-wave and related ectopy (inlay). Loss-of-function mutations lead to less I K1. It has been shown that the amplitude of I K1 is critical for the amplitude of the U-wave.5 Indeed, decreased I K1 amplitude exaggerates the U-wave and increased I K1 amplitude diminishes the U-wave.5 Based on these data, most probably, intrinsic differences in the terminal part of the ventricular action potential, critically …