Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population.

BACKGROUND & AIMS Esophageal squamous cell carcinoma (ESCC) is the predominant form of esophageal cancer in Japan. Smoking and drinking alcohol are environmental risk factors for ESCC, whereas single nucleotide polymorphisms in ADH1B and ALDH2, which increase harmful intermediates produced by drinking alcohol, are genetic risk factors. We conducted a large-scale genomic analysis of ESCCs from patients in Japan to determine the mutational landscape of this cancer. METHODS We performed whole-exome sequence analysis of tumor and nontumor esophageal tissues collected from 144 patients with ESCC who underwent surgery at 5 hospitals in Japan. We also performed single-nucleotide polymorphism array-based copy number profile and germline genotype analyses of polymorphisms in ADH1B and ALDH2. Polymorphisms in CYP2A6, which increase harmful effects of smoking, were analyzed. Functions of TET2 mutants were evaluated in KYSE410 and HEK293FT cells. RESULTS A high proportion of mutations in the 144 tumor samples were C to T substitution in CpG dinucleotides (called the CpG signature) and C to G/T substitutions with a flanking 5' thymine (called the APOBEC signature). Based on mutational signatures, patients were assigned to 3 groups, which associated with environmental (drinking and smoking) and genetic (polymorphisms in ALDH2 and CYP2A6) factors. Many tumors contained mutations in genes that regulate the cell cycle (TP53, CCND1, CDKN2A, FBXW7); epigenetic processes (MLL2, EP300, CREBBP, TET2); and the NOTCH (NOTCH1, NOTCH3), WNT (FAT1, YAP1, AJUBA) and receptor-tyrosine kinase-phosphoinositide 3-kinase signaling pathways (PIK3CA, EGFR, ERBB2). Mutations in EP300 and TET2 correlated with shorter survival times, and mutations in ZNF750 associated with an increased number of mutations of the APOBEC signature. Expression of mutant forms of TET2 did not increase cellular levels of 5-hydroxymethylcytosine in HEK293FT cells, whereas knockdown of TET2 increased the invasive activity of KYSE410 ESCC cells. Computational analyses associated the mutations in NFE2L2 we identified with transcriptional activation of its target genes. CONCLUSIONS We associated environmental and genetic factors with base substitution patterns of somatic mutations and provide a registry of genes and pathways that are disrupted in ESCCs. These findings might be used to design specific treatments for patients with esophageal squamous cancers.
The Prefoldin Complex Regulates Chromatin Dynamics during Transcription Elongation

Transcriptional elongation requires the concerted action of several factors that allow RNA polymerase II to advance through chromatin in a highly processive manner. In order to identify novel elongation factors, we performed systematic yeast genetic screening based on the GLAM (Gene Length-dependent Accumulation of mRNA) assay, which is used to detect defects in the expression of long transcription units. Apart from well-known transcription elongation factors, we identified mutants in the prefoldin complex subunits, which were among those that caused the most dramatic phenotype. We found that prefoldin, so far involved in the cytoplasmic co-translational assembly of protein complexes, is also present in the nucleus and that a subset of its subunits are recruited to chromatin in a transcription-dependent manner. Prefoldin influences RNA polymerase II the elongation rate in vivo and plays an especially important role in the transcription elongation of long genes and those whose promoter regions contain a canonical TATA box. Finally, we found a specific functional link between prefoldin and histone dynamics after nucleosome remodeling, which is consistent with the extensive network of genetic interactions between this factor and the machinery regulating chromatin function. This study establishes the involvement of prefoldin in transcription elongation, and supports a role for this complex in cotranscriptional histone eviction.
Polylactic acid/polycaprolactone nanocomposite

This article investigates the performance of polylactic acid (PLA)/polycaprolactone (PCL)/montmorillonite (MMT) nanocomposites toughened with metallocene-catalyzed linear low-density polyethylene (mLLDPE), in terms of mechanical, thermal, and morphological properties. All the results were compared and the influence of MMT and mLLDPE on the final properties was observed and reported. mLLDPE decreased the modulus and the strength of PLA/PCL and its nanocomposites due to its inherent lower rigidity compared to PLA/PCL nanocomposites. Moreover, incorporation of clay significantly increased mechanical and thermal stability of the nanocomposites. Scanning electron microscopic images confirmed that MMT acted as a compatibilizer, whereas it reduced the size of the droplets. It has been suggested that improvements in properties are related to good dispersion of clays within the matrix. However, further addition of MMT beyond 2 parts per hundred (phr) level decreases all the properties of PLA/PCL/mLLDPE/MMT nanocomposites. X-Ray diffraction patterns were used to discover the reason of reduction in the properties of PLA/PCL/mLLDPE/MMT at 4 phr. It was revealed that mLLDPE-toughened blends have intercalated structure below 4 phr MMT content as the interlayer spacing decreased at 4 phr MMT.
Screening for Celiac Disease in Type 1 Diabetes: A Systematic Review

BACKGROUND AND OBJECTIVES: Prevalence rates of type 1 diabetes (T1D) and celiac disease (CD) vary from 1.6% to 16.4% worldwide. Screening guidelines are variable and not evidence based. Our aim was to conduct a systematic review of CD in T1D. METHODS: Medline, Embase, and the Cochrane Library were searched. Studies were limited to those in English and in humans. We selected longitudinal cohort studies screening for CD in T1D with at least 5 years of follow-up. Screening rates, characteristics, and prevalence of biopsy-proven CD in people with T1D were extracted. RESULTS: We identified 457 nonduplicate citations; 48 were selected for full-text review. Nine longitudinal cohort studies in 11 157 children and adolescents with 587 cases of biopsy-proven CD met the inclusion criteria. Median follow-up was 10 years (range: 5–18 years). The weighted pooled prevalence of CD was 5.1% (95% confidence interval: 3.1–7.4%). After excluding 41 cases with CD onset before T1D, CD was diagnosed in 218 of 546 (40%) subjects within 1 year, in 55% within 2 years, and in 79% within 5 years of diabetes duration. Two studies (478 cases) reported higher rates of CD in children aged <5 years at T1D diagnosis. The duration of follow-up varied across the included studies. CD screening frequency progressively decreased with increased T1D duration. CONCLUSIONS: Because most cases of CD are diagnosed within 5 years of T1D diagnosis, screening should be considered at T1D diagnosis and within 2 and 5 years thereafter. CD screening should be considered at other times in patients with symptoms suggestive of CD. More research is required to determine the screening frequency beyond 5 years of diabetes duration.
The Potentiating Effect of ACTH and of Cortisone on Pressor Response to Intravenous Infusion of L-Nor-Epinephrine.∗

Summary 1. The pressor response to an intravenous infusion of 2.1-13.9 μg per minute of 1-nor-epinephrine was studied, using a constant rate infusion apparatus, in 3 patients before and during the administration of ACTH and cortisone. 2. Striking potentiation of the blood pressure response to nor-epinephrine was noted within 24 hours after administration of 90-180 mg ACTH daily or 150-200 mg cortisone daily. The potentiating effect disappeared within 36 hours after the omission of these agents.
Robust Matchings

We consider complete graphs with nonnegative edge weights. A p-matching is a set of p disjoint edges. We prove the existence of a maximal (with respect to inclusion) matching M that contains for any $p\le|M|$ $p$ edges whose total weight is at least ${1\over \sqrt 2}$ of the maximum weight of a p-matching. We use this property to approximate the metric maximum clustering problem with given cluster sizes.
Induction of phenotype modifying cytokines by FERMT1 mutations

Kindler syndrome (KS) is a progressive skin disorder caused by FERMT1 mutations. Early in life, KS manifests as a mechanobullous disease reflecting diminished cell adhesion, but the mechanisms of its later phenotypic features, progressive poikiloderma, and mucocutaneous fibrosis, remain elusive. The FERMT1 gene product and KS protein, kindlin‐1, is an epithelial‐specific phosphoprotein involved in integrin beta‐1 activation, without an obvious link to dermal connective tissue. Here we show how lack of intracellular kindlin‐1 in epidermal keratinocytes leads to profound changes in another skin compartment, the dermis. Kindlin‐1‐deficient keratinocytes respond to cell stress by upregulating the expression of cytokines such as IL‐20, IL‐24, TGF‐β2, IL1F5, PDGFB, and CTGF. These launch—via paracrine communication—an inflammatory response in the dermis, accompanied by the presence of TGF‐β, IL‐6, and CTGF, activation of fibroblasts and their differentiation to myofibroblasts, which secrete and deposit increased amounts of extracellular matrix proteins. These data are concordant with a model wherein repeated cycles of epidermal cell stress, cytokine secretion, dermal inflammation, and profibrotic processes underlie mucocutaneous fibrosis in KS.
Mexican-Origin Mothers’ Experiences Using Children’s Health Care Services

A focused ethnographic study in an urban Latino community in the western United States describes Mexican-origin mothers’ experiences obtaining and using health services for their children. Repeated interviews with mothers, participant observation, and children’s medical records composed the data sources. Qualitative findings suggest access to health care begins in the household, where women negotiate a working diagnosis for the children’s illness with family members and coalesce support for health care seeking. Immigrant mothers described more barriers to children’s health care than more acculturated mothers. Quantitative analyses of medical records supported this finding, with children of the least acculturated mothers demonstrating fewer well-child visits, increased emergent visits, and lower levels of immunization completeness. The results suggest health care providers can better meet the needs of Latino families with children by offering better explanations about children’s diagnoses and treatment plans and demonstrating personalismo, or a friendly, kind, and social approach to care.
The Impact of Weight Perception on the Health Behaviors of College Students

Background: Obesity has links to numerous health problems. Having an accurate perception of one's own weight is an important aspect of maintaining an appropriate weight. Purpose: The purpose of this study was to examine relationships among perceived body weight, actual body weight, body satisfaction, and selected health behaviors. Methods: The study was conducted at a southern Louisiana university with students enrolled in undergraduate classes. A total of 515 students participated in this study. Results: Students were mostly female (68%), Caucasian (68%), and freshmen (59%). Freshmen had significantly lower body mass index (BMI) measurements than seniors. Several health behaviors had significant relationships with BMI, including drinking diet soda, eating at the student union, and stress eating. Weight perception was related to scores on the Body Satisfaction Scale (BSS), where students who were more overweight scored higher on the BSS, indicating dissatisfaction. Discussion: Overall, students had an accurate perception of their weight but overreported height. The mean BMI for all students was considered overweight, indicating need for weight loss interventions. Translation to Health Education Practice: It is important to monitor a variety of health behaviors in a university student population. This information can be used to indicate areas where health education interventions are needed.
Preparation and Characterization of the PVA/MMT Composite Polymer Membrane for DMFC

A novel composite polymer electrolyte membrane composed of PVA polymer matrix and nanosized Montmorillonite (MMT) filler (2~20wt.%), was prepared by a solution casting method. The characteristic properties of the PVA/MMT composite polymer membrane were investigated using thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), scanning electron microscopy (SEM), atomic force microscopy (AFM), micro-Raman spectroscopy, and the AC impedance method. The PVA/MMT composite polymer membrane showed good thermal and mechanical properties, ionic conductivity. The PVA/10wt. %MMT composite polymer membrane with the highest ionic conductivity was around 0.0368 S cm -1 at 30 o C. The methanol permeability (P) values were 3~4×10 -6 cm 2 s -1 , which are smaller than that of Nafion 117 membrane of 5.8×10 -6 cm 2 s -1 . It was revealed that the addition of nanosized MMT fillers into the PVA matrix could markedly improve the electrochemical properties of the PVA/MMT composite membrane; it can be accomplished by a simple blend method. As a result, the PVA/MMT composite polymer appears to be a potential candidate for the DMFC applications.
CPLD-oriented Synthesis of Finite State Machines

The purpose of the paper is to present a new approach to FSM synthesis for PAL-based CPLDs. The proposed approach consists of the original method of the state assignment and PAL-oriented multi-level optimization. The aim of the proposed state assignment method is to minimize the number of the PAL-based macrocells by fitting the FSM to the structure of the CPLD as good as possible. The essence of PAL-oriented multi-level optimization is to search for multi-output implicants that can be shared by several functions. Results of experiments prove that the proposed algorithm leads to significant reduction of chip area in relation to the previously published methods and vendor-tools.
Swirling Abrasive Fluidized Bed Machining: Effect of Process Parameters on Machining Performance

Swirling Abrasive Fluidized Bed Machining (SA-FBM) is a novel variant of Fluidized Bed Machining (FBM). This research focuses on the experiments performed on copper specimens using silicon carbide abrasive particles to investigate the influence of operating parameters such as grain size, superficial velocity, and machining time on metal removal rate, transformation of surface texture, and the surface finish. The study concludes that the surface modification is faster with SA-FBM compared with conventional FBM; the initial roughness conditions of the workpiece have no effect on the maximum possible surface finish; moreover, for faster metal removal, higher superficial velocity, and for better surface finish, fine abrasive grains are preferred.
Relationship Between Degree of Left Ventricular Dysfunction, Symptom Status, and Risk of Embolic Events in Patients With Atrial Fibrillation and Heart Failure

Background and Purpose— Limited data exists regarding the relationship between left ventricular systolic dysfunction (LVSD) and heart failure (HF) symptoms and embolic risk among patients with atrial fibrillation. Methods— Participants in the Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE) trials with HF, but not randomized to oral anticoagulation, were categorized as having preserved versus reduced ejection fraction. If reduced, LVSD was classified as mild, moderate, or severe. Symptoms were quantified using New York Heart Association class.The primary outcome was a composite of stroke, transient ischemic attack, and systemic embolism. Results— There were 3487 antiplatelet-treated patients with HF at baseline. Of these patients, 969 (46.8%) had HF with preserved ejection fraction and 1103 (53.2%) had HF with reduced ejection fraction. During 3.6 years of mean follow-up, first occurrence of stroke, transient ischemic attack, or systemic embolism occurred in 386 patients.The strongest independent predictors of embolic events were age ≥75 years (hazard ratio 2.55; confidence interval, 1.85–3.53), prior stroke or transient ischemic attack (hazard ratio 2.07; 95% confidence interval, 1.65–2.60), and female sex (hazard ratio 1.37; confidence interval, 1.11–1.69). However, ejection fraction <0.50, degree of LVSD, and New York Heart Association class did not predict embolic events. Patients with HF with preserved ejection fraction exhibited similar risk of embolic events as those with HR with reduced ejection fraction: 4.3% versus 4.4% per 100 person-years (hazard ration 1.01; 95% confidence interval, 0.78–1.31). Risk of embolic events was similar across categories of LVSD (P for trend =0.96) and New York Heart Association class (P for trend =0.57). Conclusion— Among HF patients in ACTIVE, neither the presence of LVSD or degree of symptom severity influenced risk of embolic events.
Economic evaluation of a nursing-led inpatient unit: the impact of findings on management decisions of service utility and sustainability.

AIMS The nursing-led inpatient unit is designed to substitute for a period of care in acute hospital wards and to improve patient outcome prior to discharge to the community. This paper aims to evaluate the cost, from the UK National Health Service perspective, of transfer to a nursing-led inpatient unit for intermediate care and to discuss the impact of these findings to the future development and sustainability of the nursing-led inpatient unit. BACKGROUND Recent economic analyses have showed that nursing-led inpatient units are associated with increased costs of care with length of stay as the main driver of inpatient costs. METHOD The cost-effectiveness analysis was part of a randomized-controlled trial with a sample size of 175, of which 89 were in the nursing-led inpatient unit arm and 86 in the control arm. Resource use data included length of stay, investigations performed, multiprofessional input and nursing input. Clinical outcome was measured using Barthel Index, a functional status measure. RESULTS Cost per day was lower on the nursing-led inpatient unit although cost per hospital stay was higher due to significantly increased length of stay. Postdischarge community care costs were lower. The incremental cost-effectiveness ratio of the treatment was 1044 pounds sterling per point improvement of the Barthel Index. CONCLUSIONS The nursing-led inpatient unit was associated with higher costs however, the question of whether the nursing-led inpatient unit is cost-effective has not been clearly answered because of the limited follow-up period of the study. The increased cost of care on the nursing-led inpatient unit was not a major factor in local management decisions about the future of the unit. The changes in the context of service provision within which the nursing-led inpatient unit operated as a result of substantial investment in intermediate care did have a major impact.
Oxytocin receptors: oxytocin analogs, but not prostaglandins, complete with 3H-oxytocin for uptake by rat uterus.

Uterine pieces from rats pretreated with estrogen were incubated for 1 hr at 20 C with 3H—oxytocin and nonradioactive oxytocin or its analogs, [4–threonine]—oxytocin, [8–valine]—oxytocin, [8–lysine]—vasopressin. These substances competed with 3H—oxytocin for uptake in proportion to their known oxytocic activities. [4–Proline]— oxytocin, a relatively inactive analog, was not competitive in the dose range tested. Prostaglandins E1,E2, A1 and the tromethamine salt of F2α had no effect on the uptake of 3H—oxytocin. These results suggest that oxytocin receptors exist in the uterus and that the uterotonic activities of the prostaglandins are mediated via separate receptor sites. (Endocrinology 92: 104, 1973)
Peripheral Neuropathies Due to Systemic Lupus Erythematosus in China

AbstractThis article aims to analyze the frequency and clinical characteristics of peripheral neuropathy (PN) in patients with systemic lupus erythematosus (SLE). A total of 4924 SLE patients admitted to the Peking Union Medical College Hospital, Beijing, China, from January 1995 to September 2013 were included in this retrospective analysis. The individuals designated as control patients were selected from the pool of SLE patients without PN using the systematic sampling method of 1:2 during the same time.The prevalence of SLE-associated PN (SLE-PN) in SLE patients was 1.5% (73/4924). Seventy-nine cases of PN affected 73 patients and 6 of these patients (8.2%) presented with 2 types of PN. Among the 7 types of PN, polyneuropathy was the most frequent and was diagnosed in 47 cases (59.5%); the remaining patients suffered from mononeuropathy (13.9%), cranial neuropathy (12.7%), myasthenia gravis (10.1%), autonomic neuropathy (2.5%), or acute inflammatory demyelinating polyradiculoneuropathy (1.3%). Five patients developed PN before the onset of SLE (3 out of 5 patients had myasthenia gravis). The most common PN-related symptoms were myasthenia and numbness (50.6%), followed by pain in affected regions (35.9%). PN symptoms were relieved in a majority of the patients (76.7%) after treatment. Compared with non-SLE-PN patients, patients with SLE-PN had a higher frequency of fever (65.8% vs 45.9%, P < 0.01), mucocutaneous involvement (73.9% vs 36.3%, P < 0.01), arthritis (42.5% vs 28.1%, P < 0.05), myositis (17.8% vs 5.5%, P < 0.01), and central nervous system involvement (38.4% vs 21.9%, P < 0.05) as well as being positive for the anti-Sm antibody (31.4% vs 18.8%), immunoglobulin G (IgG) elevation (53.6% vs 37.1%, P < 0.01), and reduction in complement 3 (54.8% vs 36.9%, P < 0.05). A statistically significant difference was found between the Systemic Lupus Erythematosus Disease Activity Index scores in SLE-PN patients compared with the non-SLE-PN patients (P < 0.05). Multivariate logistic regression showed that the only risk factor for PN was IgG elevation (odds ratio = 2.553, 1.224–5.327, P = 0.012). The prevalence of PN in SLE occurs more frequently in patients with an active form of the disease. IgG elevation is a risk factor for SLE-PN and should be assessed in these patients. Young female patients with myasthenia gravis should be closely monitored for the development of SLE.
MADS-box Transcription Factor OsMADS25 Regulates Root Development through Affection of Nitrate Accumulation in Rice

MADS-box transcription factors are vital regulators participating in plant growth and development process and the functions of most of them are still unknown. ANR1 was reported to play a key role in controlling lateral root development through nitrate signal in Arabidopsis. OsMADS25 is one of five ANR1-like genes in Oryza Sativa and belongs to the ANR1 clade. Here we have investigated the role of OsMADS25 in the plant’s responses to external nitrate in Oryza Sativa. Our results showed that OsMADS25 protein was found in the nucleus as well as in the cytoplasm. Over-expression of OsMADS25 significantly promoted lateral and primary root growth as well as shoot growth in a nitrate-dependent manner in Arabidopsis. OsMADS25 overexpression in transgenic rice resulted in significantly increased primary root length, lateral root number, lateral root length and shoot fresh weight in the presence of nitrate. Down-regulation of OsMADS25 in transgenic rice exhibited significantly reduced shoot and root growth in the presence of nitrate. Furthermore, over-expression of OsMADS25 in transgenic rice promoted nitrate accumulation and significantly increased the expressions of nitrate transporter genes at high rates of nitrate supply while down-regulation of OsMADS25 produced the opposite effect. Taken together, our findings suggest that OsMADS25 is a positive regulator control lateral and primary root development in rice.