Miracle-dz/UniFAR-FTUs huggingface dataset:
Progesterone Receptor B (PGR-B) Is Partially Methylated in Eutopic Endometrium From Infertile Women With Endometriosis

Endometriosis is frequently related to infertility and little is known about the mechanisms underlying this association. Some studies point to an endometrial factor involved in this condition, which could compromise embryo implantation. Progesterone plays crucial role in endometrial receptivity by acting through progesterone receptor (PGR) isoforms PR-A and PR-B whose expression is epigenetically regulated by DNA methylation, in a specific promoter region for each isoform. Epigenetic changes in PGR-A and PGR-B may be related to progesterone resistance of endometriosis-related infertility. In order to better understand the mechanisms involved in endometrial receptivity, this case–control study aimed to compare the methylation pattern of PGR-A and PGR-B in eutopic endometrium from infertile women with and without endometriosis during the secretory phase. Endometrial biopsies from 19 patients (10 infertile women with endometriosis and 9 infertile controls) with regular cycles were performed during the secretory phase and were dated according to Noyes’ criteria. The percentage of DNA methylation at PGR-A and PGR-B was carried out by high-resolution melting assay. The PGR-A gene showed 0% of DNA methylation (unmethylated) in both control and endometriosis groups. However, PGR-B gene showed a partially methylated pattern in majority of the patients (n = 7), with methylation percentage corresponding to 50%, while in the control group the percentage of methylation was 20% (hypomethylated; P = .04). The increased percentage of methylation at PGR-B may be related to reduced gene expression, which could compromise the endometrial receptivity in patients with endometriosis.
Crystal structure of human mitochondrial trifunctional protein, a fatty acid β-oxidation metabolon

Significance Fatty acid β-oxidation is the major energy-producing process in all tissues and is performed by four consecutive reactions that cleave fatty acids. Mitochondrial trifunctional protein (TFP) performs the last three of these four reactions. Herein, we report the crystal structure of human TFP and compare and contrast this with the recently reported cryo-EM structure. The crystal structure reveals the channel through which the substrate/product can pass from the first reaction site to the second and onto the third, thereby minimizing leakage of the intermediates/product to the outside of the protein. Our findings provide a better understanding of how this enzyme functions and reveal insight into the development of inhibitors or agonists for the regulation of fatty acid degradation. Membrane-bound mitochondrial trifunctional protein (TFP) catalyzes β-oxidation of long chain fatty acyl-CoAs, employing 2-enoyl-CoA hydratase (ECH), 3-hydroxyl-CoA dehydrogenase (HAD), and 3-ketothiolase (KT) activities consecutively. Inherited deficiency of TFP is a recessive genetic disease, manifesting in hypoketotic hypoglycemia, cardiomyopathy, and sudden death. We have determined the crystal structure of human TFP at 3.6-Å resolution. The biological unit of the protein is α2β2. The overall structure of the heterotetramer is the same as that observed by cryo-EM methods. The two β-subunits make a tightly bound homodimer at the center, and two α-subunits are bound to each side of the β2 dimer, creating an arc, which binds on its concave side to the mitochondrial innermembrane. The catalytic residues in all three active sites are arranged similarly to those of the corresponding, soluble monofunctional enzymes. A structure-based, substrate channeling pathway from the ECH active site to the HAD and KT sites is proposed. The passage from the ECH site to the HAD site is similar to those found in the two bacterial TFPs. However, the passage from the HAD site to the KT site is unique in that the acyl-CoA intermediate can be transferred between the two sites by passing along the mitochondrial inner membrane using the hydrophobic nature of the acyl chain. The 3′-AMP-PPi moiety is guided by the positively charged residues located along the “ceiling” of the channel, suggesting that membrane integrity is an essential part of the channel and is required for the activity of the enzyme.
A Novel Root-Knot Nematode Resistance QTL on Chromosome Vu01 in Cowpea

The root-knot nematode (RKN) species Meloidogyne incognita and M. javanica cause substantial root system damage and suppress yield of susceptible cowpea cultivars. The narrow-based genetic resistance conferred by the Rk gene, present in some commercial cultivars, is not effective against Rk-virulent populations found in several cowpea production areas. The dynamics of virulence within RKN populations require a broadening of the genetic base of resistance in elite cowpea cultivars. As part of this goal, F1 and F2 populations from the cross CB46-Null (susceptible) x FN-2-9-04 (resistant) were phenotyped for M. javanica induced root-galling (RG) and egg-mass production (EM) in controlled growth chamber and greenhouse infection assays. In addition, F2:3 families of the same cross were phenotyped for RG on field sites infested with Rk-avirulent M. incognita and M. javanica. The response of F1 to RG and EM indicated that resistance to RKN in FN-2-9-04 is partially dominant, as supported by the degree of dominance in the F2 and F2:3 populations. Two QTL associated with both RG and EM resistance were detected on chromosomes Vu01 and Vu04. The QTL on Vu01 was most effective against aggressive M. javanica, whereas both QTL were effective against avirulent M. incognita. Allelism tests with CB46 x FN-2-9-04 progeny indicated that these parents share the same RKN resistance locus on Vu04, but the strong, broad-based resistance in FN-2-9-04 is conferred by the additive effect of the novel resistance QTL on Vu01. This novel resistance in FN-2-9-04 is an important resource for broadening RKN resistance in elite cowpea cultivars.
Use of Complementary and Alternative Medicine by Patients with Irritable Bowel Syndrome According to the Roma IV Criteria: A Single-Center Italian Survey

Aim: This study was conducted to evaluate the impact of complementary and alternative medicine (CAM) in patients with irritable bowel syndrome (IBS) as assessed by the Rome IV criteria. Methods: Consecutive patients referring for IBS were re-evaluated according to the Rome IV criteria. Demographic features and characteristics potentially associated with the use of CAM were collected. A validated, self-administered, survey questionnaire dealing with CAM and patients’ level of knowledge, motivation, perception, and information seeking-behavior toward the use of CAM was analyzed. Multivariate logistic regression analysis was performed in order to identify predictors of CAM use among participants. Results: Among 156 patients claiming IBS, 137 (88%) met the Rome IV criteria, and 62 of them (45%) were CAM users. Biologically based therapy was the most chosen CAM (78%). Significant risk factors (adjusted odds ratio, 95% confidence interval) for the use of CAM were female gender (7.22, 2.31–22.51), a higher BMI (1.16, 1.02–1.33), and a good knowledge of CAM (4.46, 1.73–11.45), while having children was a protective factor (0.25, 0.07–0.95). Only 19% of patients used CAM due to medical advice and over half (51%) thought it was a “more natural” approach. Although a minority of patients (16%) had full satisfaction from CAM, 81% of users would repeat the CAM experience for their IBS symptoms. Conclusions: The widespread use of CAM in IBS, the patients’ belief in its safety, and their willingness to re-use it suggest that knowledge of health-care providers and patient education should be improved.
Money, Managed Care, and Medicaid Initiatives Matter: Patient-centered Medical Home Capacity in School-based Health Centers

Abstract:School-based health centers (SBHCs) have been suggested as potential medical homes, but may experience challenges implementing the patient-centered medical home (PCMH) model. It is currently unknown if there are PCMH variations among different types of SBHCs. The purpose of this study was to examine the associations between SBHC characteristics and PCMH capacity. Using 2013–2014 National Census of School-Based Health Centers data, SBHC PCMH Index scores were calculated and used as outcomes in linear regression models examining associations between PCMH capacity and SBHC characteristics. The mean PCMH capacity score for all SBHCs was 68.59%, with higher scores in the Comprehensive Care domain than in the Care Quality domain. Managed care arrangements, Medicaid PCMH initiatives, more funding sources, and higher patient billing activity were all positively associated with overall PCMH capacity. Having higher percentages of students who are members of racial/ethnic minority groups was negatively associated with overall PCMH capacity.
Cardiomyopathy: A Systematic Review of Disease-Causing Mutations in Myosin Heavy Chain 7 and Their Phenotypic Manifestations

Background:Mutations in myosin heavy chain 7 (MYH7) commonly cause cardiomyopathy. However, the relationship between mutation location, cardiomyopathy type, change in amino acid composition and disease severity is poorly understood. This systematic review aims to provide, on a large scale, important insights into the role mutations in MYH7 play in cardiomyopathy. Methods: The literature was searched from 1966 to March 2009. The mutation location, type of mutation and disease type and severity were documented. When the severity of disease was known, the change in charge and hydropathy of the mutation was determined. Where appropriate, either a χ2 test was used or a relative risk ratio was calculated in order to evaluate the data. Results:The data presented in this study demonstrate that there are proportionately more mutations in the head and neck regions of this gene than in the tail. Importantly, mutations in the head of the gene, those that cause large changes in the hydropathy of the amino acid and non-conservative mutations are more likely to lead to a severe phenotype. Conclusions: This study suggests that mutation location in the MYH7 gene and changes in amino acid composition can have a negative impact on the disease outcome in individuals with cardiomyopathy.
Siblings of patients with rheumatoid arthritis are at increased risk of acute coronary syndrome

Objectives To investigate a potential shared susceptibility between rheumatoid arthritis (RA) and acute coronary syndrome (ACS) by estimation of the risk of ACS among full siblings of patients with RA. Methods By linking nation-wide Swedish registers, we identified a cohort of patients with new-onset RA 1996–2016, age- and sex-matched (5:1) general population comparator subjects, full siblings of RA and comparator subjects, and incident ACS events through 31 December 2016. We used Cox regression to estimate the HR of ACS among patients with RA and the siblings of patients with RA versus the general population, overall and stratified by RA serostatus. We explored the impact of traditional cardiovascular (CV) risk factors on the observed associations. Results We identified 8109 patients with incident RA, and 11 562 full siblings of these. Compared with the general population, the HR of ACS in RA was 1.46 (95% CI 1.28 to 1.67) and 1.22 (95% CI 1.09 to 1.38) among their siblings. The increased risks seemed confined to seropositive RA (patients: 1.52 [1.30 to 1.79], their siblings: 1.27 [1.10 to 1.46]); no significant risk increase was observed among siblings of patients with seronegative RA (HR 1.13 [95% CI 0.92 to 1.39]). Adjustment for 19 traditional CV risk factors did not appreciably alter these associations. Conclusion Siblings of patients with RA are at increased risk of ACS, suggesting shared susceptibility between RA and ACS, indicating the need and potential for additional cardio-preventive measures in RA (and their siblings).
Incidence of referred carpal tunnel syndrome and carpal tunnel release surgery in the general population: Increase over time and regional variations

Purpose: To investigate the change in incidence of referred carpal tunnel syndrome (CTS) and carpal tunnel release (CTR) surgery over time and regional variations. Methods: From the nationwide patient registry, we identified all adult individuals who had received first-time CTS diagnosis (International Classification of Diseases, 10th Revision code G560) at secondary or tertiary level and first-time CTR surgery during the period of 9 years. Results: From 2001 through 2009, the incidence (per 100,000 person-years) of CTS diagnosed at secondary or tertiary level increased from 216 to 243 in women and from 95 to 119 in men and of CTR from 117 to 168 in women and from 52 to 78 in men. The mean annual increase in first-time CTR (95% confidence interval) was 5.1% (4.7–5.4) in women and 6.2% (5.6–6.7) in men. The age-standardized 3-year (2007–2009) incidence varied significantly across Sweden’s 21 counties; compared to the county with the lowest incidence of CTR, the incidence rates in the other counties were higher by 6–152% (mean 60%) in women and by 20–182% (mean 85%) in men. The proportion of CTS-diagnosed individuals treated with surgery varied across counties from 53% to 81% in women and from 51% to 77% in men. Conclusion: The incidence of referred CTS and of CTR surgery increased over time in both sexes, with large regional variations found in the incidence rates and in the proportion of individuals treated with surgery.
ADAM17 selectively activates the IL‐6 trans‐signaling/ERK MAPK axis in KRAS‐addicted lung cancer

Oncogenic KRAS mutations are major drivers of lung adenocarcinoma (LAC), yet the direct therapeutic targeting of KRAS has been problematic. Here, we reveal an obligate requirement by oncogenic KRAS for the ADAM17 protease in LAC. In genetically engineered and xenograft (human cell line and patient‐derived) KrasG12D‐driven LAC models, the specific blockade of ADAM17, including with a non‐toxic prodomain inhibitor, suppressed tumor burden by reducing cellular proliferation. The pro‐tumorigenic activity of ADAM17 was dependent upon its threonine phosphorylation by p38 MAPK, along with the preferential shedding of the ADAM17 substrate, IL‐6R, to release soluble IL‐6R that drives IL‐6 trans‐signaling via the ERK1/2 MAPK pathway. The requirement for ADAM17 in KrasG12D‐driven LAC was independent of bone marrow‐derived immune cells. Furthermore, in KRAS mutant human LAC, there was a significant positive correlation between augmented phospho‐ADAM17 levels, observed primarily in epithelial rather than immune cells, and activation of ERK and p38 MAPK pathways. Collectively, these findings identify ADAM17 as a druggable target for oncogenic KRAS‐driven LAC and provide the rationale to employ ADAM17‐based therapeutic strategies for targeting KRAS mutant cancers.
Laterally Movable Triple Electrodes Actuator toward Low Voltage and Fast Response RF-MEMS Switches

A novel actuator toward a low voltage actuation and fast response in RF-MEMS (radio frequency micro-electro-mechanical systems) switches is reported in this paper. The switch is comprised of laterally movable triple electrodes, which are bistable by electrostatic forces applied for not only the on-state, but also the off-state. The bistable triple electrodes enable the implementation of capacitive series and shunt type switches on a single switch, which leads to high isolation in spite of the small gap between the electrodes on the series switch. These features of the actuator are effective for a low voltage and fast response actuation in both the on- and off-state. The structure was designed in RF from a mechanical point of view. The laterally movable electrodes were achieved using a simple, low-cost two-mask process with 2.0 µm thick sputtered aluminum. The characteristics of switching response time and actuation voltage were 5.0 µs and 9.0 V, respectively.
Diagnostic performance of 16- and 64-section spiral CT for coronary artery bypass graft assessment: meta-analysis.

PURPOSE To perform a meta-analysis to evaluate the accuracy of 16- and 64-section spiral computed tomography (CT) to help assess coronary artery bypass grafts (CABGs). MATERIALS AND METHODS The MEDLINE, Cochrane library, and BioMed Central databases were searched for relevant original articles published up to May 2007. Major criteria for article inclusion were that it (a) used multisection CT as a diagnostic test for the assessment of significant lesions (occlusion or >50% stenosis) of CABG, (b) used a 16- or 64-section scanner, and (c) used coronary angiography as the reference standard. After data extraction, the analysis was performed according to a random-effects model. Between-study statistical heterogeneity was also assessed by using the Cochran Q chi(2) test. RESULTS Of 158 screened articles, 15 fulfilled all inclusion criteria. Graft assessability (including distal anastomosis) ranged from 78%-100% among all included studies (mean, 92.4%; 90% with 16- and 96% with 64-section CT; P < .001). Statistical heterogeneity was observed for specificity and positive likelihood ratio (LR), justifying the use of the random-effects model. The analysis, pooled from 15 studies (723 patients, 2023 CABGs), provided the following results for the assessment of graft obstruction (occlusion and >50% stenosis): sensitivity, 97.6% (95% confidence interval [CI]: 96%, 98.6%); specificity, 96.7% (95% CI: 95.6%, 97.5%); positive predictive value, 92.7% (95% CI: 90.5%, 94.6%); negative predictive value, 98.9% (95% CI: 98.2%, 99.4%); positive LR, 23.42 (95% CI: 13.69, 40.07); negative LR, 0.045 (95% CI: 0.028, 0.071); and diagnostic odds ratio, 780.32 (95% CI: 379.12, 1606.1). CONCLUSION Multisection CT provided high accuracy for the evaluation of CABG obstruction in assessable conduits, and might be used as a noninvasive tool for the evaluation of suspected graft dysfunction in patients who are at high risk for complications from coronary angiography.
Migration of titanium dioxide from PET/TiO2 composite film for polymer-laminated steel

ABSTRACT PET/TiO2 composite film is the most widely used film for polymer-laminated steel, and the migration of TiO2 is very important for the safety evaluation of its packaged food. Microwave digestion, wet digestion and dry ashing were used for pretreatment of composite film to determine the content of TiO2 in composite film. Migration tests were carried out at 40°C, 60°C and 80°C 4% using acetic acid and 50% ethanol as the acid and ester food simulants. The migration amount of TiO2 was determined by inductively coupled plasma optical emission spectrometry (ICP-OES). With increasing temperature and time, the migration of TiO2 increased. In 4% acetic acid, the migration amount of TiO2 at 40°C for 10 days was 1.88 mg kg−1 and the migration amount at 80°C for 8 h was 3.32 mg kg−1, indicating that the effect of temperature on migration was more obvious. Under the same conditions, the migration amount of TiO2 in 4% acetic acid was greater than in 50% ethanol. X-ray diffraction (XRD), scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimeter (DSC) were used to analyse the crystal structure, morphology, chemical groups and thermal properties of the film before and after the migration tests. The results showed that filmTiO2 had a stable rutile type crystal structure and it was almost uniformly distributed. PET and TiO2 were combined with strong chemical bonds. After TiO2 migration, the crystallinity and the glass transition temperature (Tg) of the film decreased, but the change of melting temperature (Tm) was not obvious.
Outbreak of Eremothecium coryli Fruit Rot of Tomato in California.

A ripe fruit rot of tomato (Lycopersicon esculentum) associated with stink bug (Euschistus conspersus) feeding caused extensive losses in the Sacramento Valley of California in 1998. Portions of several fields were abandoned at harvest due to fruit rot levels >30%. Symptoms included a soft, water-soaked rot often surrounding a firm, dark green island. Entire fruit sometimes became watery and soft. The ascomycetous yeast, Eremothecium coryli, characterized by spindle-shaped ascospores with long, thin, whip-like terminal appendages (1), was consistently isolated from diseased tissue plated on V8 or potato dextrose agar amended with tetracycline. Ripe tomato fruit were inoculated with a 0.1-ml suspension of 1.5 × 105 ascospores per ml injected to a depth of ≈4 mm to simulate stink bug probing. Fruit were placed in plastic containers and, in initial tests, were held at room temperature. In subsequent tests, inoculated fruit were maintained at constant temperatures of 20, 25, 30, or 35°C. Controls included inoculum either placed on the fruit surface or injected with sterilized water. Each treatment consisted of one to four fruit in two to four replications. All experiments were repeated. Lesions were visible within 5 days after inoculation and were >25 mm in diameter after 7 days. Progression of rot occurred at all temperatures but was fastest at 30 and 35°C. Controls remained symptomless. E. coryli was reisolated from infected fruit. This is the first documentation of field-level losses caused by E. coryli associated with stink bug feeding. Isolates are maintained in the Herman J. Phaff Collection of Yeast and Yeast-like Microorganisms at the University of California, Davis. Reference: (1) G. S. de Hoog et al. 1998. Eremothecium Borzi emend. Kurtzman. Pages 201-208 in: The Yeasts-A Taxonomic Study. C. P. Kurtzman and J. W. Fell, eds. Elsevier Scientific Publishers, Amsterdam.
Dietary intake of people with severe mental illness: systematic review and meta-analysis

Background Severe mental illness (SMI) is thought to be associated with lower diet quality and adverse eating behaviours contributing towards physical health disparities. A rigorous review of the studies looking at dietary intake in psychotic disorders and bipolar disorder is lacking. Aims To conduct a systematic, comprehensive evaluation of the published research on dietary intake in psychotic disorders and bipolar disorder. Method Six electronic databases were searched for studies reporting on dietary intakes in psychotic disorders and bipolar disorder. Dietary-assessment methods, and dietary intakes, were systematically reviewed. Where possible, data was pooled for meta-analysis and compared with healthy controls. Results In total, 58 eligible studies were identified. People with SMI were found to have significantly higher dietary energy (mean difference 1332 kJ, 95% CI 487–2178 kJ/day, P = 0.002, g = 0.463) and sodium (mean difference 322 mg, 95% CI 174–490 mg, P < 0.001, g = 0.414) intake compared with controls. Qualitative synthesis suggested that higher energy and sodium intakes were associated with poorer diet quality and eating patterns. Conclusions These dietary components should be key targets for preventative interventions to improve weight and other physical health outcomes in people with SMI. Declaration of interest S.B. T. and E.T. have clinical dietitian appointments within the South Eastern Sydney Local Health District and do not receive any further funding.