Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling the structural and dynamical changes of the epithelial calcium channel TRPV5 caused by the A563T variation based on the structure of TRPV6

Abstract TRPV5, transient receptor potential cation channel vanilloid subfamily member 5, is an epithelial Ca2+ channel that plays a key role in the active Ca2+ reabsorption process in the kidney. A single nucleotide polymorphism (SNP) rs4252499 in the TRPV5 gene results in an A563T variation in the sixth transmembrane (TM) domain of TRPV5. Our previous study indicated that this variation increases the Ca2+ transport function of TRPV5. To understand the molecular mechanism, a model of TRPV5 was established based on the newly deposited structure of TRPV6 that has 83.1% amino acid identity with TRPV5 in the modeled region. Computational simulations were performed to study the structural and dynamical differences between the TRPV5 variants with A563 and T563. Consistent with the TRPV1-based simulation, the results indicate that the A563T variation increases the contacts between residues 563 and V540, which is one residue away from the key residue D542 in the Ca2+-selective filter. The variation enhanced the stability of the secondary structure of the pore region, decreased the fluctuation of residues around residue 563, and reduced correlated and anti-correlated motion between monomers. Furthermore, the variation increases the pore radius at the selective filter. These findings were confirmed using simulations based on the recently determined structure of rabbit TRPV5. The simulation results provide an explanation for the observation of enhanced Ca2+ influx in TRPV5 caused by the A563T variation. The A563T variation is an interesting example of how a residue distant from the Ca2+-selective filter influences the Ca2+ transport function of the TRPV5 channel. Communicated by Ramaswamy H. Sarma
Treatment for in‐stent restenosis requiring rotational atherectomy

OBJECTIVES This study aimed to evaluate the outcomes of patients with in-stent restenosis (ISR) who underwent rotablation (RA) followed by balloon angioplasty (BA), drug-eluting stent (DES) implantation, or drug-coated balloon (DCB) angioplasty. BACKGROUND Interventional treatment of ISR is occasionally challenging. Despite the availability of various percutaneous treatments, the optimal solution remains unclear. METHODS AND RESULTS A total of 200 patients with ISR who underwent RA were retrospectively identified from our institutional database. Clinical outcomes at 12 months and independent predictors of target lesion revascularization (TLR) were assessed. Of patients, 90, 55, and 55 underwent BA, DES implantation, and DCB angioplasty, respectively. The incidence of all-cause death, cardiac death, and hospitalization due to heart failure was low in all groups. Moreover, no definite stent thrombosis was observed in the three groups. The TLR rate of BA, DES implantation, and DCB angioplasty following RA for ISR were 40.7%, 35.0%, and 27.3%, respectively. The adjusted outcomes for TLR using the inverse probability of treatment weighting method based on propensity scores indicated that DCB angioplasty following RA was superior to BA after RA. Intraprocedural complications, which could be successfully managed with interventional treatment, were identified in only three cases. CONCLUSIONS TLR at 12 months is dismal. RA is not effective for ISR requiring RA. In unfavorable settings, DCB angioplasty following RA is the most effective treatment option in patients with ISR requiring debulking strategy.
Incidence of Total Hip and Knee Replacement in UK Patients with Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial skeleton manifested by back pain and progressive stiffness. However, it is not uncommon for peripheral joints to be involved; the underlying histopathology of which is characterized by subchondral bone inflammation that can result in joint erosion and eventual destruction. There have been emerging data on the need for joint replacement surgery among patients with AS1,2,3, although these data have mainly originated from cohorts of patients under hospital care or registry data and therefore may be more selective of severe disease. Our aim here was to better understand the need for joint replacement surgery in the overall AS population in the United Kingdom by using National Health Service (NHS) primary care electronic medical records to determine the incidence of total hip replacement (THR) and total knee replacement (TKR) following diagnosis of AS. We identified patients in the Clinical Practice Research Datalink (CPRD) with a first diagnosis of AS within the United Kingdom between January 1, 1995, and March 31, 2014. We excluded patients with a diagnosis of > 1 type of inflammatory arthritis. CPRD is a primary … Address correspondence to Dr. D. Prieto-Alhambra, Botnar Research Centre, Windmill Road, Oxford, OX3 7LD, UK. E-mail: daniel.prietoalhambra{at}ndorms.ox. ac.uk
AgRP/NPY Neuron Excitability Is Modulated by Metabotropic Glutamate Receptor 1 During Fasting

The potential to control feeding behavior via hypothalamic AgRP/NPY neurons has led to many approaches to modulate their excitability—particularly by glutamatergic input. In the present study using NPY-hrGFP reporter mice, we visualize AgRP/NPY neuronal metabotropic glutamate receptor 1 (mGluR1) expression and test the effect of fasting on mGluR1 function. Using the pharmacological agonist dihydroxyphenylglycine (DHPG), we demonstrate the enhanced capacity of mGluR1 to drive firing of AgRP/NPY neurons after overnight fasting, while antagonist 3-MATIDA reduces firing. Further, under synaptic blockade we demonstrate that DHPG acts directly on AgRP/NPY neurons to create a slow inward current. Using an in vitro approach, we show that emulation of intracellular signals associated with fasting by forskolin enhances DHPG induced phosphorylation of extracellularly regulated-signal kinase (1/2) in GT1-7 cell culture. We show in vivo that blocking mGluR1 by antagonist 3-MATIDA lowers fasting induced refeeding. In summary, this study identifies a novel layer of regulation on AgRP/NPY neurons integrated with whole body energy balance.
[Distribution of ejaculatory duct openings and the method of entering the vesiculoscope into the seminal vesicle].

Objective To search for an optimal method of entering the seminal vesiculoscope based on the distribution of ejaculatory duct openings. METHODS Fifty-six patients with refractory hemospermia underwent seminal vesiculoscopy in our hospital from July 2014 to December 2016. We observed the positions of the ejaculatory duct openings under the seminal vesiculoscope, analyzed their distribution, and explored the optimal methods of entering the seminal vesiculoscope according to the success rate of operation, experience of the operators, video data and operation records. RESULTS Based on the distribution of the positions, the ejaculatory duct openings of the patients were classified into types Ⅰ (the included angle between the medial area of the prostatic utricle edge tangent and the inferior utricle region ≤45°), Ⅱ (the included angle between the lateral area of the prostatic utricle edge tangent and the inferior utricle region >45°), and Ⅲ (the ejaculatory duct opening abnormal or located in the prostatic utricle), which accounted for 42.9% (24/56), 48.2% (27/56) and 8.9% (5/56), respectively. The success rate of entering the vesiculoscope through the natural passage was 83.3% for type Ⅰ and 29.6% for type Ⅱ openings. A bypass method was used for all the 5 cases of type Ⅲ by making a blunt puncture through the lateral wall of the prostatic utricle. Follow-up was completed in 54 of the patients, of whom 52 (96.3%) showed disappearance or significant improvement of the hemospermia symptoms at 1－3 months postoperatively. CONCLUSIONS Type Ⅱ ejaculatory duct openings are the most commonly seen clinically, and then come types Ⅰ and Ⅲ. For patients with type Ⅰ ejaculatory duct openings, the best way of entering the seminal vesiculoscope was through the natural passage, while for those with types Ⅱ and Ⅲ, the bypass method is recommended.
Examining interactions between genetic risk for alcohol problems, peer deviance, and interpersonal traumatic events on trajectories of alcohol use disorder symptoms among African American college students

Abstract Numerous studies have demonstrated that genetic and environmental factors interact to influence alcohol problems. Yet prior research has primarily focused on samples of European descent and little is known about gene–environment interactions in relation to alcohol problems in non-European populations. In this study, we examined whether and how genetic risk for alcohol problems and peer deviance and interpersonal traumatic events independently and interactively influence trajectories of alcohol use disorder symptoms in a sample of African American students across the college years (N = 1,119; Mage = 18.44 years). Data were drawn from the Spit for Science study where participants completed multiple online surveys throughout college and provided a saliva sample for genotyping. Multilevel growth curve analyses indicated that alcohol dependence genome-wide polygenic risk scores did not predict trajectory of alcohol use disorder symptoms, while family history of alcohol problems was associated with alcohol use disorder symptoms at the start of college but not with the rate of change in symptoms over time. Peer deviance and interpersonal traumatic events were associated with more alcohol use disorder symptoms across college years. Neither alcohol dependence genome-wide polygenic risk scores nor family history of alcohol problems moderated the effects of these environmental risk factors on alcohol use disorder symptoms. Our findings indicated that peer deviance and experience of interpersonal traumatic events are salient risk factors that elevate risk for alcohol problems among African American college students. Family history of alcohol problems could be a useful indicator of genetic risk for alcohol problems. Gene identification efforts with much larger samples of African descent are needed to better characterize genetic risk for alcohol use disorders, in order to better understand gene–environment interaction processes in this understudied population.
Microbe Profile: Saccharomyces eubayanus, the missing link to lager beer yeasts

Saccharomyces eubayanus was described less than 10 years ago and its discovery settled the long-lasting debate on the origins of the cold-tolerant yeast responsible for lager beer fermentation. The largest share of the genetic diversity of S. eubayanus is located in South America, and strains of this species have not yet been found in Europe. One or more hybridization events between S. eubayanus and S. cerevisiae ale beer strains gave rise to S. pastorianus, the allopolyploid yeasts responsible for lager beer production worldwide. The identification of the missing progenitor of lager yeast opened new avenues for brewing yeast research. It allowed not only the selective breeding of new lager strains, but revealed also a wild yeast with interesting brewing abilities so that a beer solely fermented by S. eubayanus is currently on the market.
Subxiphoid pneumonectomy: the new frontier?

Over the last decade there has been a significant drive towards minimally invasive thoracic surgery. The reported benefits of video-assisted thoracic surgery (VATS) over open surgery include reduced postoperative pain, reduced postoperative complications, reduced length of hospital-stay and period of recovery to normal function (1-4). With increased experience, more advanced procedures are now reportedly performed by VATS in high volume centres, including sleeve and carinal resections (5,6).
Post mortem troponin T analysis in sudden death: Is it useful?

INTRODUCTION Cardiac-related diseases contributed approximately 50-60% of sudden natural death cases. This study aimed to describe the cardiac troponin T (cTnT) findings in post mortem subjects irrespective of the cause and manner of death, and the possible use of post mortem serum cTnT as a modality in investigating sudden natural death. METHODS The study samples comprised 140 subjects aged 18 to 50 years old, natural and unnatural causes of sudden death brought to the Department of Forensic Medicine, Hospital Sungai Buloh (HSgB) and Hospital Sultanah Aminah Johor Bahru (HSAJB) for a period of 12 months. The subjects were categorised into 5 groups: cardiovascular disease (CVD), sudden unexplained death (SUD), thoracic trauma (TT), non-thoracic trauma (NTT) and other diseases (OD). RESULTS Median troponin concentration in cases of CVD, SUD, TT, NTT, and OD were 0.51 μg/L, 0.17 μg/L, 0.62 μg/L, 0.90 μg/L and 0.51 μg/L respectively. We found no significant difference of troponin T level in different causes of death (p ≥ 0.05). NTT has the highest median troponin concentration with 0.90 μg/L, SUD possessed the lowest median concentration with 0.17 μg/L. CONCLUSION Troponin T is neither specific nor useful as cardiac biomarker for post mortem sample. Therefore, it may not be a useful diagnostic tool at autopsy.
Finite LTL Synthesis with Environment Assumptions and Quality Measures

In this paper, we investigate the problem of synthesizing strategies for linear temporal logic (LTL) specifications that are interpreted over finite traces -- a problem that is central to the automated construction of controllers, robot programs, and business processes. We study a natural variant of the finite LTL synthesis problem in which strategy guarantees are predicated on specified environment behavior. We further explore a quantitative extension of LTL that supports specification of quality measures, utilizing it to synthesize high-quality strategies. We propose new notions of optimality and associated algorithms that yield strategies that best satisfy specified quality measures. Our algorithms utilize an automata-game approach, positioning them well for future implementation via existing state-of-the-art techniques.
Spontaneous coronary artery dissection: from expert consensus statements to evidence-based medicine.

Spontaneous coronary artery dissection (SCAD) represents an increasingly recognized cause of acute coronary syndrome (ACS), especially in young females. Novel diagnostic insights obtained from intracoronary imaging and the frequent association with fibromuscular dysplasia (FMD), have recently enriched our understanding of this unique clinical entity. Recently, two scientific statements from both sides of the Atlantic, summarizing the available information on SCAD, have been simultaneously published. These should help to guide the clinical management of these challenging patients. Major collaborative research efforts are required to move from expert-based recommendations to evidence-base medicine.
The Abnormality of Topological Asymmetry in Hemispheric Brain Anatomical Networks in Bipolar Disorder

Convergent evidences have demonstrated a variety of regional abnormalities of asymmetry in bipolar disorder (BD). However, little is known about the alterations in hemispheric topological asymmetries. In this study, we used diffusion tensor imaging to construct the hemispheric brain anatomical network of 49 patients with BD and 61 matched normal controls. Graph theory was then applied to quantify topological properties of the hemispheric networks. Although small-world properties were preserved in the hemispheric networks of BD, the degrees of the asymmetry in global efficiency, characteristic path length, and small-world property were significantly decreased. More changes in topological properties of the right hemisphere than those of left hemisphere were found in patients compared with normal controls. Consistent with such changes, the nodal efficiency in patients with BD also showed less rightward asymmetry mainly in the frontal, occipital, parietal, and temporal lobes. In contrast to leftward asymmetry, significant rightward asymmetry was found in supplementary motor area of BD, and attributed to more deficits in nodal efficiency of the left hemisphere. Finally, these asymmetry score of nodal efficiency in the inferior parietal lobule and rolandic operculum were significantly associated with symptom severity of BD. Our results suggested that abnormal hemispheric asymmetries in brain anatomical networks were associated with aberrant neurodevelopment, and providing insights into the potential neural biomarkers of BD by measuring the topological asymmetry in hemispheric brain anatomical networks.
A randomized trial of the efficacy and safety of azilsartan medoxomil combined with chlorthalidone

Introduction: We measured the effects of azilsartan medoxomil co-administered with chlorthalidone 25 mg in stage 2 hypertension. Methods: Azilsartan medoxomil 40 or 80 mg plus chlorthalidone were compared with placebo plus chlorthalidone once daily in a randomized, double-blind, 6-week trial. The primary endpoint was change from baseline in 24-hour mean systolic blood pressure by ambulatory blood pressure monitoring. Results: Patients (N=551; mean age 59 years; 51.7% men) were randomly assigned to placebo plus chlorthalidone (n=184), azilsartan medoxomil 40 mg plus chlorthalidone (n=185), or azilsartan medoxomil 80 mg plus chlorthalidone (n=182). Baseline systolic blood pressures were similar among groups. After 6 weeks, least squares mean (standard error) reductions with azilsartan medoxomil 40 mg and 80 mg plus chlorthalidone were similar in magnitude (−31.7 (1.0) and −31.3 (1.0) mmHg, respectively), but greater than chlorthalidone alone (−15.9 (1.0) mmHg). Hypotension and serum creatinine elevations were more frequent with azilsartan medoxomil plus chlorthalidone than chlorthalidone alone (reversed with drug discontinuation). Notably, plasma potassium reduction of 0.43 meq/L with chlorthalidone was attenuated to 0.13 and 0.05 meq/L by azilsartan medoxomil 40 mg and 80 mg, respectively. Conclusion: Azilsartan medoxomil 40 mg or 80 mg plus chlorthalidone 25 mg was significantly more efficacious than chlorthalidone alone in reducing blood pressure and was well tolerated. Clinicaltrial.gov, https://clinicaltrials.gov/ct2/show/NCT00591773, NCT00591773
Changes in metabolism but not myocellular signaling by training with CHO‐restriction in endurance athletes

Carbohydrate (CHO) restricted training has been shown to increase the acute training response, whereas less is known about the acute effects after repeated CHO restricted training. On two occasions, the acute responses to CHO restriction were examined in endurance athletes. Study 1 examined cellular signaling and metabolic responses after seven training‐days including CHO manipulation (n = 16). The protocol consisted of 1 h high‐intensity cycling, followed by 7 h recovery, and 2 h of moderate‐intensity exercise (120SS). Athletes were randomly assigned to low (LCHO: 80 g) or high (HCHO: 415 g) CHO during recovery and the 120SS. Study 2 examined unaccustomed exposure to the same training protocol (n = 12). In Study 1, muscle biopsies were obtained at rest and 1 h after 120SS, and blood samples drawn during the 120SS. In Study 2, substrate oxidation and plasma glucagon were determined. In Study 1, plasma insulin and proinsulin C‐peptide were higher during the 120SS in HCHO compared to LCHO (insulin: 0 min: +37%; 60 min: +135%; 120 min: +357%, P = 0.05; proinsulin C‐peptide: 0 min: +32%; 60 min: +52%; 120 min: +79%, P = 0.02), whereas plasma cholesterol was higher in LCHO (+15–17%, P = 0.03). Myocellular signaling did not differ between groups. p‐AMPK and p‐ACC were increased after 120SS (+35%, P = 0.03; +59%, P = 0.0004, respectively), with no alterations in p‐p38, p‐53, or p‐CREB. In Study 2, glucagon and fat oxidation were higher in LCHO compared to HCHO during the 120SS (+26–40%, P = 0.03; +44‐76%, P = 0.01 respectively). In conclusion, the clear respiratory and hematological effects of CHO restricted training were not translated into superior myocellular signaling after accustomization to CHO restriction.
Quantitative proteomics of forebrain subcellular fractions in fragile X mental retardation 1 knockout mice following acute treatment with 2‐Methyl‐6‐(phenylethynyl)pyridine: Relevance to developmental study of schizophrenia

The fragile X mental retardation 1 knockout (Fmr1 KO) mouse replicates behavioral deficits associated with autism, fragile X syndrome, and schizophrenia. Less is known whether protein expression changes are consistent with findings in subjects with schizophrenia. In the current study, we used liquid chromatography tandem mass spectrometry (LC‐MS/MS) proteomics to determine the protein expression of four subcellular fractions in the forebrains of Fmr1 KO mice vs. C57BL/6 J mice and the effect of a negative allosteric modulator of mGluR5—2‐Methyl‐6‐(phenylethynyl)pyridine (MPEP)—on protein expression. Strain‐ and treatment‐specific differential expression of proteins was observed, many of which have previously been observed in the brains of subjects with schizophrenia. Western blotting verified the direction and magnitude of change for several proteins in different subcellular fractions as follows: neurofilament light protein (NEFL) and 2′,3′‐cyclic‐nucleotide 3′‐phosphodiesterase (CNP) in the total homogenate; heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC) and heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) in the nuclear fraction; excitatory amino acid transporter 2 (EAAT2) and ras‐related protein rab 3a (RAB3A) in the synaptic fraction; and ras‐related protein rab 35 (RAB35) and neuromodulin (GAP43) in the rough endoplasmic reticulum fraction. Individuals with FXS do not display symptoms of schizophrenia. However, the biomarkers that have been identified suggest that the Fmr1 KO model could potentially be useful in the study of schizophrenia.
The usage and meaning of "mentioned" ("wspomniany") and "described" ("opisany") metatext markers in Polish scientific texts

The usage and meaning of mentioned (wspomniany) and described (opisany) metatext markers in Polish scientific textsMetatext markers (MMs) are defined as expressions used in a text to inform readers of its structure or relations between its elements (Fraser, 1999; Goldman & Rakestraw, 2000; Schiffrin, 1988). In this paper the usage of two MMs "mentioned" ("wspomniany") and "described" ("opisany") in scientific texts is described and the relation between their meaning and usage is analysed. In Study 1, the frequency, scope and direction of the MM is analysed in a corpus of peer-reviewed scientific texts in Polish. In Experiment 2, participants decided whether to use the aforementioned MMs to fill gaps in short scientific texts. The results of both experiments suggest that while the meaning of an MM may influence its usage, this relation may be affected by the size of the whole text. Użycie i znaczenie operatorów metatekstowych wspomniany i opisany w tekstach naukowych po polskuOperatory metatekstowe (OM) to wyrażenia informujące czytelnika o strukturze tekstu, w którym zostały umieszczone, oraz o relacjach pomiędzy jego elementami (Fraser, 1999; Goldman & Rakestraw, 2000; Schiffrin, 1988). W poniższej pracy zostało opisane użycie dwóch OM wspomniany i opisany w tekstach naukowych, przeanalizowano także relację pomiędzy ich znaczeniem i używaniem. W badaniu 1 zostały przeanalizowane częstość użycia, zakres i ukierunkowanie OM w tekstach naukowych pisanych po polsku. W badaniu 2 czytelnicy decydowali o tym, czy umieścić dodatkowy OM w krótkim tekście naukowym. Wyniku obydwu badań wskazują, że znaczenie OM może wpływać na sposób jego używania, ale wpływ ten zmienia się wraz z wielkością tekstu.