Miracle-dz/UniFAR-FTUs huggingface dataset:
Transthyretin Suppresses Amyloid- β secretion by Interfering with Processing of The Amyloid- β Precursor Protein

In Alzheimer’s disease (AD) most hippocampal and cortical neurons show increased staining with anti-transthyretin (TTR) antibodies. Genetically programmed over-expression of wild type human TTR suppressed the neuropathologic and behavioral abnormalities in APP23 AD model mice and TTR-A β complexes have been isolated from some human AD brains and those of APP23 transgenic mice. In the present study in vitro NMR analysis showed interaction between the hydrophobic thyroxine binding pocket of TTR and the cytoplasmic loop of the C99 fragment released by β -secretase cleavage of A β PP with K d = 86±9 µM. In cultured cells expressing both proteins the interaction reduced phosphorylation of C99 (at T668) and suppressed its cleavage by γ -secretase significantly decreasing A β secretion. Coupled with its previously demonstrated capacity to inhibit A β aggregation (with the resultant cytotoxicity in tissue culture) and its regulation by HSF1 these findings indicate that TTR can behave as a stress responsive multimodal suppressor of AD pathogenesis.
Circulating cell-free messenger RNA secretome characterization of primary sclerosing cholangitis

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease characterized by multi-focal bile duct strictures. To date, underlying molecular mechanisms of PSC remain unclear and therapeutic options for PSC patients are limited. We performed cell-free messenger RNA (cf-mRNA) next generation sequencing (RNA-Seq) to characterize the circulating transcriptome of PSC and non-invasively investigate potentially bioactive signals that are associated with PSC. METHODS: Serum cf-mRNA profiles were compared among 50 individuals with PSC, 20 healthy controls, and 235 individuals with non-alcoholic fatty liver disease (NAFLD). Tissue and cell type-of-origin genes that are dysregulated in subjects with PSC were evaluated. Subsequently, diagnostic classifiers were built using PSC dysregulated cf-mRNA genes. RESULTS: Differential expression analysis of the cf-mRNA transcriptomes of PSC and healthy controls resulted in identification of 1407 dysregulated genes. Furthermore, differentially expressed genes between the liver diseases (PSC, NAFL, Non-Alcohol Steatohepatitis (NASH)) and healthy controls shared common genes known to be involved in liver pathophysiology. In particular, genes from liver- and specific cell type-origin, including hepatocyte, hepatic stellate cells and Kupffer cells, were highly abundant in cf-mRNA of subjects with PSC. Gene cluster analysis revealed that liver-specific genes dysregulated in PSC form a distinct cluster which corresponded to a subset of the PSC subject population. Finally, we developed a cf-mRNA classifier using liver-specific genes which discriminated PSC from healthy control subjects using gene transcripts of liver origin. CONCLUSIONS: Blood-based whole transcriptome cf-mRNA profiling revealed high abundance of liver-specific genes in PSC subject sera which may be used to diagnose PSC patients. We identified several unique cf-mRNA profiles of subjects with PSC. These findings may also have utility for non-invasive molecular stratification of subjects with PSC for pharmacotherapy safety and response studies.
A Cross-sectional Study to Assess Beta-Cell Function in Individuals with Recently Diagnosed Young-Onset Type 2 Diabetes Mellitus and Its’ Complications

The primary objective of this study was to assess beta cell function of recently diagnosed young onset type 2 diabetes mellitus (T2DM) individuals. The secondary objective examined the association between C- peptide with metabolic factors and diabetes complications. A cross-sectional study was conducted for young onset T2DM individuals aged 18-35 years with disease duration not more than 5 years. Plasma basal and stimulated C-peptide was measured before and after intravenous glucagon injection. Demographic data, medical history and complications were obtained from medical records and clinical assessment. A total of 113 participants with young onset T2DM with mean age of 29 years and median disease duration of 24 months were included in this study. The median (interquartile range) basal and stimulated C-peptide was 619 (655) pmol/L and 1231(1024) pmol/L . Adequate beta cell function was present in 78-86% of the participants based on the basal and stimulated C-peptide levels. Obesity and hypertension were independently associated with higher basal and stimulated C-peptide while diabetic kidney disease was independently associated with higher basal C-peptide. We found most recently diagnosed young onset T2DM have adequate beta cell function. Elevated C-peptide levels associated with obesity, hypertension and diabetic kidney disease suggests insulin resistance as the key driving factor for complications.
The role of epidemic spreading in seizure dynamics and epilepsy surgery

Abstract Epilepsy surgery is the treatment of choice for drug-resistant epilepsy patients, but only leads to seizure freedom for roughly two in three patients. To address this problem, we designed a patient-specific epilepsy surgery model combining large-scale magnetoencephalography (MEG) brain networks with an epidemic spreading model. This simple model was enough to reproduce the stereo-tactical electroencephalography (SEEG) seizure propagation patterns of all patients (N = 15), when considering the resection areas (RA) as the epidemic seed. Moreover, the goodness of fit of the model predicted surgical outcome. Once adapted for each patient, the model can generate alternative hypothesis of the seizure onset zone and test different resection strategies in silico. Overall, our findings indicate that spreading models based on patient-specific MEG connectivity can be used to predict surgical outcomes, with better fit results and greater reduction on seizure propagation linked to higher likelihood of seizure freedom after surgery. Finally, we introduced a population model that can be individualized by considering only the patient-specific MEG network, and showed that it not only conserves but improves the group classification. Thus, it may pave the way to generalize this framework to patients without SEEG recordings, reduce the risk of overfitting and improve the stability of the analyses.
An analysis of patterns of distribution of buprenorphine in the United States using ARCOS, Medicaid, and Medicare databases

Opioid overdose remains a problem in the United States despite pharmacotherapies, such as buprenorphine, in the treatment of opioid use disorder. This study characterized changes in buprenorphine use. Using the Drug Enforcement Administration's ARCOS, Medicaid, and Medicare claims databases, patterns in buprenorphine usage in the United States from 2018 to 2020 were analyzed by examining percentage changes in total grams distributed and changes in grams per 100 K people in year‐to‐year usage based on ZIP code and state levels. For ARCOS from 2018 to 2019 and 2019 to 2020, total buprenorphine distribution in grams increased by 16.2% and 12.6%, respectively. South Dakota showed the largest statewide percentage increase in both 2018–2019 (66.1%) and 2019–2020 (36.7%). From 2018 to 2019, the ZIP codes ND‐577 (156.4%) and VA‐222 (−82.1%) had the largest and smallest percentage changes, respectively. From 2019 to 2020, CA‐932 (250.2%) and IL‐603 (−36.8%) were the largest and smallest, respectively. In both 2018–2019 and 2019–2020, PA‐191 had the second highest increase in grams per 100K while OH‐452 was the only ZIP code to remain in the top three largest decreases in grams per 100K in both periods. Among Medicaid patients in 2018, there was a nearly 2000‐fold difference in prescriptions per 100k Medicaid enrollees between Kentucky (12 075) and Nebraska (6). Among Medicare enrollees in 2018, family medicine physicians and other primary care providers were the top buprenorphine prescribers. This study not only identified overall increases in buprenorphine availability but also pronounced state‐level differences. Such geographic analysis can be used to discern which public policies and regional factors impact buprenorphine access.
ACE and ACE 2 in kidney disease

Renin angiotensin system (RAS) activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme (ACE)-angiotensin II (Ang II)-Ang II type 1 (AT1) axis is considered to control the effects of RAS activation on renal disease. However, since its discovery in 2000 ACE2 has also been demonstrated to have a significant impact on the RAS. The synthesis and catabolism of Ang II are regulated via a complex series of interactions, which involve ACE and ACE2. In the kidneys, ACE2 is expressed in the proximal tubules and less strongly in the glomeruli. The synthesis REVIEW 74 February 6, 2015|Volume 4|Issue 1| WJN|www.wjgnet. com ACE and ACE2 in kidney disease World Journal of Nephrology W J N Submit a Manuscript: http://www.wjgnet. com/esps/ Help Desk: http://www.wjgnet. com/esps/helpdesk.aspx DOI: 10.5527/wjn.v4. i1.74 World J Nephrol 2015 February 6; 4(1): 74-82 ISSN 2220-6124 (online) © 2015 Baishideng Publishing Group Inc. All rights reserved.
Adipogenic risk factor differences between Korean and Caucasian adults – potential role of plasma free fatty acid and adiponectin

Objective— Asian adults are at greater risk for metabolic abnormalities (insulin resistance, dyslipidemia) at the same BMI than are Caucasians. Elevated FFA and decreased adiponectin are linked with these same metabolic abnormalities. Research Design and Methods— We tested the hypothesis that fasting plasma FFA are greater and adiponectin concentrations are lower in Korean that Caucasian adults matched for age, sex and BMI. Plasma FFA and adiponectin concentrations were analyzed using a microflourometric assay and radioimmunoassay, respectively. Results— Fasting plasma FFA concentrations were not different (P=0.51) between Korean and Caucasian subjects 208 (183–232) vs. 215 (168–262) (median and 95% CI). Despite similar body composition in the two groups, the plasma adiponectin concentrations in Koreans were significantly lower than Caucasians in men, women and total subgroups (adjusted mean ± SEM; 4.9 ± 0.8 vs. 9.1 ± 0.8 μ g/ml, P= 0.004, 8.9 ± 1.0 vs. 13.2 ± 1.0 μ g/ml, P =0.006, and 6.5 ± 0.6 vs. 11.1 ± 0.6 μ g/ml, P< 0.001), respectively, after adjustment for differences in height, weight and fat free mass as covariates. Men had lower plasma adiponectin concentrations than women in both Korean (P=0.041) and Western adults (P<0.001). Conclusion— Plasma adiponectin levels are lower in Korean than age-, sex- and body mass index-matched Caucasian adults whereas fasting plasma FFA are not different. To the extent adipogenic factors account for ethnic differences in metabolic disease risk, our data suggests that differences in the regulation of adiponectin may predispose towards greater metabolic abnormalities in Asians than Caucasians at comparable BMI levels.
Trends in Substance Use Prevention Program Participation among Adolescents in the United States

Purpose: To examine national trends in adolescent participation in substance use prevention programming (SUPP). Methods: We examine fifteen years of cross-sectional data (2002–2016) from the National Survey on Drug Use and Health. Main outcomes were participation in past-year school and community-based SUPP (no/yes). Logistic regression was used to examine trends in the prevalence of participation. Results: Participation in school-based SUPP decreased significantly from 48% among adolescents in 2002–2003 to 40% in 2015–2016, a 16.5% proportional decline. Significant declines for school-based participation were observed in all demographic and drug involvement subgroups examined. Youth participation in community-based SUPP also decreased significantly. However, this downward trend was significant only among younger teens, females, youth in very low (< $20,000) and moderate ($40,000-$74,999) income households, and in rural areas. Conclusions: Participation in SUPP has decreased since the early 2000s, with noteworthy declines among Latino youth and youth from rural areas and socioeconomically disadvantaged backgrounds.
Predicting the transition to chronic pain six months after an ED visit for acute pain. A prospective cohort study

Background. — Acute pain may transition to chronic pain, a potentially debilitating illness. Objectives. — We determined how often acute pain transitions to chronic pain among ED patients and whether persistent pain 1 week after the ED visit was associated with chronic pain. Methods. — An observational cohort study conducted in two EDs. We included adults with acute pain (≤10 days) if an oral opioid was prescribed. Exclusion criteria were recent opioid use or use of any analgesics regularly prior to onset of the pain. Research associates interviewed patients during the ED visit, and 1 week and 6 months later. The primary outcome, chronic pain, was defined as pain on >50% of days since ED discharge. We constructed logistic regression models to evaluate the association between persistent pain 1 week after an ED visit and chronic pain while adjusting for demographic and treatment variables. Results. — During a 9-month period, we approached 733 patients for participation and enrolled 484. 450/484(93%) provided one week outcome data and 410/484(85%) provided six month outcome data. One week after the ED visit, 348/453(77%, 95%CI:73, 80%) patients reported pain in the affected area. New onset chronic pain at six months was reported by 110/408 (27%, 95%CI: 23, 31%) patients. Presence of pain one week after ED visit was associated with chronic pain (OR3.6, 95%CI:1.6,8.5). of patients pain to chronic pain within six months. of pain week after the
Tenectin is a novel α PS2 β PS integrin ligand required for wing morphogenesis and male genital looping in Drosophila

Morphogenesis of the adult structures of holometabolous insects is regulated by ecdysteroids and juvenile hormones and involves cell-cell interactions mediated in part by the cell surface integrin receptors and their extracellular matrix (ECM) ligands. These adhesion molecules and their regulation by hormones are not well characterized. We describe the gene structure of a newly described ECM molecule, tenectin, and demonstrate that it is a hormonally regulated ECM protein required for proper morphogenesis of the adult wing and male genitalia. Tenectin’s function as a new ligand of the PS2 integrins is demonstrated by both genetic interactions in the fly and by cell spreading and cell adhesion assays in cultured cells. Its interaction with the PS2 integrins is dependent on RGD and RGD-like motifs. Tenectin’s function in looping morphogenesis in the development of the male genitalia led to experiments that demonstrate a role for PS integrins in the execution of left-right asymmetry. larval and pupal molts. These hormones regulate gene expression patterns required for development.
Diacylglycerol-dependent Binding Recruits PKC (cid:1) and RasGRP1 C1 Domains to Speciﬁc Subcellular Localizations in Living T Lymphocytes □ V

Diacylglycerol (DAG) signaling relies on the presence of conserved domain 1 (C1) in its target proteins. Phospholipase C–dependent generation of DAG after T cell receptor (TCR) triggering is essential for the correct immune response onset. Accordingly, two C1-containing proteins expressed in T lymphocytes, Ras guanyl nucleotide-releasing protein1 (Ras- GRP1) and protein kinase C (cid:1) (PKC (cid:1) ), were shown to be fundamental for T-cell activation and proliferation. Although containing the same regulatory domain, they are proposed to relocate to distinct subcellular locations in response to TCR triggering. Here we studied intracellular localization of RasGRP1 and PKC (cid:1) C1 domains in living Jurkat T cells. The results demonstrate that, in the absence of signiﬁcant primary sequence differences, the C1 domains of these proteins show speciﬁc localization within the cell and distinct responses to pharmacological stimulation and TCR triggering. These differences help explain the divergent localization and distinct functional roles of the full-length proteins, which contains them. The properties of these DAG-binding modules allow their characterization as functional markers that discriminate between DAG pools. Finally, we show that by binding to different diacylglycerol forms, overexpression of distinct C1 modules can attenuate DAG-dependent signals originating from the plasma or internal membranes. This is shown by analyzing the contribution of these two lipid pools to PLC-dependent Ras activation in response to TCR triggering.
Developing and Sharing ESP Resources: the Online Teaching Project at the UPV

Different initiatives have been put into practice by the Universitat Politecnica de Valencia in order to help students be better prepared for a globalised labour market in which both the mastery of ICT and the use of English are essential for communication. An example of this is the Online Teaching Project, which was initially aimed at encouraging teachers to design reusable, high-quality multimedia resources to be shared through online platforms such as RiuNet, Politube and OCW. The project’s initial goal was successfully achieved and its participants were therefore ready to face bigger challenges, namely encouraging students to become part of the materials development process by means of a project of digital storytelling. Keywords: Digital storytelling, ESP, OCW, Politube, RiuNet;
The GLASS-JWST Early Release Science Program. I. Survey Design and Release Plans

The GLASS-JWST Early Release Science (hereafter GLASS-JWST-ERS) Program will obtain and make publicly available the deepest extragalactic data of the ERS campaign. It is primarily designed to address two key science questions, namely, “what sources ionized the universe and when? ” and “how do baryons cycle through galaxies? ”, while also enabling a broad variety of first look scientific investigations. In primary mode, it will obtain NIRISS and NIRSpec spectroscopy of galaxies lensed by the foreground Hubble Frontier Field cluster, Abell 2744. In parallel, it will use NIRCam to observe two fields that are offset from the cluster center, where lensing magnification is negligible, and which can thus be effectively considered blank fields. In order to prepare the community for access to this unprecedented data, we describe the scientific rationale, the survey design (including target selection and observational setups), and present pre-commissioning estimates of the expected sensitivity. In addition, we describe the planned public releases of high-level data products, for use by the wider astronomical community.
Analytic theory of ideal-MHD vertical displacements in tokamak plasmas

An analytic derivation of the relevant dispersion relation for vertical displacements in shaped tokamak plasmas is presented, valid for arbitrary values of the ellipticity parameter. The theory is developed within the framework of the reduced ideal-MHD model. A nearby, perfectly conducting wall can provide passive feedback stabilization of vertical displacements on the ideal-MHD timescale. The mechanism for passive stabilization relies on image currents induced on the metallic wall. However, if the plasma extends to the magnetic separatrix, where magnetic X-points are located, as in the case of a divertor tokamak configuration, perturbed axisymmetric currents carried by the plasma in the vicinity of the X-points are triggered. It is shown that these X-point currents can provide passive feedback stabilization, even in the absence of a nearby wall. X-point currents are excited due to the resonant nature of magnetic X-points with respect to toroidal axisymmetric perturbations. An intermediate case, where the plasma boundary is located just inside the magnetic separatrix, is also analyzed, providing additional insight into the stabilization mechanism.
Clustered structural and functional plasticity of dendritic spines

The configuration of synaptic circuits underlies their ability to process and store information. Research on dendritic spines has revealed that their structural and functional alterations are clustered along the parent dendrite. Here we review the evidence supporting such notion of clustered synaptic plasticity, discuss its functional implications and possible contributing factors, and suggest potential strategies to deal with open challenges.
Nonstationarity and conjugacy: Utilities for data patch work: SEP

I design and explain programs for parceling a planar data set into an array of patches (small planes) that may overlap. The conjugate takes the patches and adds them back together into a data plane. Because of overlap, the original data set is not recovered unless weighting functions are used. Any weighting function can be used in any patch. I provide a seamless reconstruction with code in which you can incorporate any linear operator. Finally, I code time and space variable 2-D ltering using invariant ltering in patches, taking care that lters do not run oo the boundaries of each patch and using triangular weighting functions to merge patches.
Pericardial Tamponade and Large Pericardial Effusions

In 50 patients treated from January 1998 through March 2002 for pericardial effusion and tamponade, we retrospectively investigated the efficacy of percutaneous placement of an indwelling pericardial catheter guided by 2-dimensional echocardiography and fluoroscopy. We also investigated causation. In 80% of the patients, we were able to determine specific causes through clinical, serologic, and cytologic investigation: cancer in 15 patients, chronic renal failure in 11, systemic lupus erythematosus in 2, rheumatoid arthritis in 2, Dressler syndrome in 2, tuberculosis in 1, blunt chest trauma in 1, purulent pericarditis in 1, and probably viral pericarditis in 5. No specific cause could be determined in 10 patients (20%). We did not observe any complication due to the procedure. Two patients died during hospitalization. After hospitalization, 9 patients with metastatic cancer died within 3 months. A 2nd percutaneous drainage procedure was required in 2 cancer patients. Recurrence of pericardial effusion and tamponade and the requirement of pericardiectomy occurred in 2 patients with perfusion of unknown cause and in 1 patient with perfusion due to rheumatoid arthritis. Histologic examination of pericardial tissue in patients with idiopathic disease showed fibrinous pericarditis but no causal factor. In the group with idiopathic pericardial effusion, 2 patients with multiple mediastinal lymphadenopathy underwent mediastinal exploration; biopsy revealed nonspecific lymphadenitis and fibrinous pericarditis. In patients with large pericardial effusions and tamponade, the specific cause was in most cases already known or obtained by initial clinical and laboratory investigation. Sufficient cardiac decompression was achieved by percutaneous pigtail catheter drainage. (Tex Heart Inst J 2004;31:398-403)
A total cost minimization control for wastewater treatment process by using extremum seeking control

This paper presents a real-time optimal control scheme based on a total cost index (TCI) by using the so-called extremum seeking control (ESC). The ESC searches the minimum value of a given performance index where the TCI consisting of the operational cost and the effluent quality cost is used as the index. An improved ESC is proposed where a transformed TCI by monotonically increasing function is utilized to improve the convergence property of the ESC while keeping the argument of the optimal point invariant. The feasibility of the ESC is tested for two types of pseudo-anaerobic-oxic process control: one is the return sludge recycle ratio control, and the other is the aeration control for an alternate zone which can be anaerobic or aerobic depending on the influent condition. Simulation study illustrates that the proposed ESC is able to find a near optimal point successfully and the TCI can be reduced by about 2.7 to 3.8% compared with that of a typical operating condition.