Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Outcomes After Percutaneous Coronary Intervention in Elderly Patients, Including 10 628 Nonagenarians: Insights From a Japanese Nationwide Registry (J‐PCI Registry)

Background Scarce data exist about the outcomes after percutaneous coronary intervention (PCI) in old patients. This study sought to provide an overview of PCI in elderly patients, especially nonagenarians, in a Japanese large prospective nationwide registry. Methods and Results We analyzed 562 640 patients undergoing PCI (≥60 years of age) from 1018 Japanese hospitals between 2014 and 2016 in the J‐PCI (Japanese percutaneous coronary intervention) registry. Among them, 10 628 patients (1.9%), including 6780 (1.2%) with acute coronary syndrome (ACS) and 3848 (0.7%) with stable coronary artery disease, were ≥90 years of age. We investigated differences in characteristics and in‐hospital outcomes among sexagenarians, septuagenarians, octogenarians, and nonagenarians. Older patients were more frequently women and had a greater frequency of heart failure and chronic kidney disease than younger patients. In addition, older patients had a higher rate of in‐hospital mortality, cardiac tamponade, cardiogenic shock after PCI, and bleeding complications requiring blood transfusion. Nonagenarians had the highest risk of in‐hospital mortality (odds ratio, 3.60; 95% CI, 3.10–4.18 in ACS; odds ratio, 6.24; 95% CI, 3.82–10.20 in non‐ACS) and bleeding complications (odds ratio, 1.79; 95% CI, 1.35–2.36 in ACS; odds ratio, 2.70; 95% CI, 1.68–4.35 in non‐ACS) when referenced to sexagenarians. More important, transradial intervention was an inverse independent predictor of both in‐hospital mortality and bleeding complications. Conclusions Older patients, especially nonagenarians, carried a greater risk of in‐hospital death and bleeding compared with younger patients after PCI. Transradial intervention might contribute to risk reduction for periprocedural complications in elderly patients undergoing PCI.
Single Institution trial of anthracycline‐ and taxane‐based chemotherapy for operable breast cancer: The ASTER study

The efficacy of anthracycline‐ and taxane‐based chemotherapy for perioperative treatment of breast cancer (BC) has been established. No superiority of a cytotoxic regimen has been demonstrated, provided that administration of an anthracycline and a taxane is warranted. The ASTER study was designed to investigate the safety of 6 months of perioperative chemotherapy with Doxorubicin and Paclitaxel, followed by Cyclophosphamide, Methotrexate, and 5‐Fluorouracil. ASTER enrolled patients with cT2‐3 N0‐1 or pT1‐2 N1‐3 BC, from November 2008 to August 2011. Treatment consisted of Doxorubicin 60 mg/sm, Paclitaxel 200 mg/sm q21 (AT) for three cycles followed by Cyclophosphamide 600 mg/sm, Methotrexate 40 mg/sm, 5‐Fluorouracil 600 mg/sm d1,8 q28 (CMF) for three cycles, in either neo‐adjuvant or adjuvant setting. All HER‐positive patients received targeted therapy with Trastuzumab for 1 year. Disease‐free and overall survival (DFS and OS, respectively) were estimated according to Kaplan‐Meier method. Three hundred and thirty patients were enrolled, where 77.9% of cases were treated in an adjuvant setting; 65.5% received breast conservative surgery, 72.4% axillary dissection. 75.5% of cases presented estrogen receptor positivity, 66.7% progesterone receptor positivity; 18.5% of patients presented HER2‐positive BC, 16.1% triple negative disease. Twenty‐eight (8.5%) developed grade III‐IV hematologic toxicity; nine patients (2.7%) developed grade III neurological toxicity. Loco‐regional DFS was 99.6% at 1 year, 97.1% at 5 years, 95.9% at 7 years. Corresponding distant DFS was 98.4%, 90.2%, and 88.8%. One, 5, and 7‐year OS was 99.6%, 94.9%, and 91.2%, respectively. Chemotherapy with ATx3→CMFx3 is confirmed safe and effective at 6.7 years follow‐up. These results appear comparable to those reported in regulatory trials of most commonly prescribed anthracycline and taxane‐based regimens.
Pulmonary Rehabilitation Improves Sleep Quality in Chronic Lung Disease

Abstract Sleep-related disorders are common in patients with chronic obstructive pulmonary disease (COPD) and, possibily, other lung disorders. Exercise has been shown to improve sleep disturbances. In patients with COPD, pulmonary rehabilitation (PR) produces important health benefits with improvement in symptoms, exercise tolerance, and quality of life. However, the effect of PR on sleep quality remains unknown. The aim of this observational study was to evaluate sleep quality in patients with chronic lung disease and the role of PR as a non-pharmacologic treatment to improve sleep. Sixty-four patients with chronic lung disease enrolled in an 8-week comprehensive PR program, and completed the study (48% male; obstructive [72%], restrictive [20%], mixed [8%]; 44% on supplemental oxygen). Baseline spirometry [mean (SD)]: FEV1% pred = 48.9 (17.4), FVC% pred = 72.5 (18.1), and FEV1/FVC% = 53.1 (18.9). Exercise tolerance and questionnaires related to symptoms, health-related quality of life (HRQL), and sleep quality using the Pittsburgh Sleep Quality Index (PSQI) were obtained before and after PR. 58% reported poor sleep quality (PSQI > 5) at baseline. Sleep quality improved by 19% (p = 0.017) after PR, along with significant improvements in dyspnea, exercise tolerance, self-efficacy, and HRQL. Sleep quality in patients with chronic lung disease was poor. In addition to expected improvements in symptoms, exercise tolerance, and HRQL after PR, the subgroup of patients with COPD had a significant improvement in sleep quality. These findings suggest that PR may be an effective, non-pharmacologic treatment option for sleep problems in patients with COPD.
Is having any prenatal care associated with lower infant mortality in West Africa? Evidence from the Demographic and Health Surveys

Abstract Although developing countries may find it difficult to provide adequate prenatal care, it is likely that they can provide at least some. We examined associations of prenatal care with infant mortality in West Africa. We used data from the Demographic and Health Surveys (n = 57,322) and proportional hazards regression models to estimate the risk of infant mortality. Having any prenatal care was associated with lower infant mortality risk in all but the poorest wealth quintile, with 56% lower risk in the wealthiest quintile (95% confidence interval [CI] 0.28–0.69). Even limited prenatal care may significantly reduce infant mortality in developing countries.
NID1 variant associated with occipital cephaloceles in a family expressing a spectrum of phenotypes

Autosomal dominant Dandy‐Walker malformation and occipital cephalocele (ADDWOC) is a rare, congenital, and incompletely penetrant malformation that is considered to be part of the Dandy‐Walker spectrum of disorders. Affected individuals often present with an occipital cephalocele with a bony skull defect, but typically have normal neurological development. Here, we report on a three‐generation family in which individuals have variable phenotypes that are consistent with the ADDWOC spectrum: arachnoid cysts in the proband and his maternal grandfather, an occipital cephalocele in the proband and his brother, and a small bony defect in the proband's mother. Whole exome sequencing identified a rare heterozygous variant in NID1 (NM_002508.2:c.1162C>T, (p.Gln388Ter)) in the proband, his brother, and his mother. Sanger sequencing confirmed the presence of this variant in the maternal grandfather. The identical c.1162C>T variant was previously identified in variably affected members of a three‐generation family with ADDWOC. This case report provides further evidence that variants in NID1 may be clinically relevant for the development of a phenotype that is consistent with ADDWOC, and extends the phenotype of NID1‐associated ADDWOC to include arachnoid cysts. Given that the Dandy‐Walker malformation itself is not a pre‐requisite to this spectrum of phenotypes, we also suggest a novel term for the NID1‐associated disorder in order to give emphasis to this phenotypic variability: “Autosomal Dominant Posterior Fossa Anomalies with Occipital Cephaloceles. ”
Detection of Erosions in Sacroiliac Joints of Patients with Axial Spondyloarthritis Using the Magnetic Resonance Imaging Volumetric Interpolated Breath-hold Examination

Objective. The volumetric interpolated breath-hold examination (VIBE) magnetic resonance imaging (MRI) technique can visualize erosive cartilage defects in peripheral joints. We evaluated the ability of VIBE to detect erosions in sacroiliac joints (SIJ) of patients with axial spondyloarthritis (axSpA) compared to the established T1-weighted MRI sequence and computed tomography (CT). Methods. MRI (T1-weighted and VIBE) and CT scans of SIJ of 109 patients with axSpA were evaluated by 2 blinded readers based on SIJ quadrants (SQ). Erosions were defined according to Assessment of Spondyloarthritis international Society (ASAS) definitions. Scores were recorded if readers were in agreement. Results. Erosions were less frequently detected by CT (153 SQ) than by T1-weighted MRI (182 SQ; p = 0.008) and VIBE-MRI (199 SQ; p < 0.001 vs CT and p = 0.031 vs T1-weighted MRI). Taking CT as the gold standard, the sensitivity of VIBE-MRI (71.2%) was higher than that for T1-weighted MRI (63.4%), with similar specificity (87.3% vs 88%, respectively). In linear regression analysis, younger age was significantly associated with occurrence of erosions independently in VIBE-MRI (β = 0.384, p < 0.001) and T1-weighted MRI (β = 0.369, p < 0.001) compared to CT. Conclusion. The VIBE-MRI sequence was more sensitive than T1-weighted MRI in identifying erosive damage in the SIJ, especially in younger patients. This might be due to the ability of VIBE-MRI to identify structural changes in the cartilage that have not yet extended to the underlying bone, where CT seems to be superior.
Generation of insulin‐producing hepatocyte‐like cells from human Wharton's jelly mesenchymal stem cells as an alternative source of islet cells

Islet cell transplantation, as a treatment of type 1 diabetes, has a lot of complexity such as allograft rejections and an insufficient number of donors. The liver can be used as a replacement for endogenous insulin production. Hepatocytes can inherently respond to glucose levels and secrete proteins. Utilization of mesenchymal stem cells for curing diabetes represents a major focus of recent investigations. As a new choice for transplantation, we have proposed glucose‐regulated insulin‐producing hepatocyte‐like cells, which produce insulin dependent on glucose levels. We have transfected human Wharton's jelly mesenchymal stem cells with the special construct, which included homology arms and glucose‐responsive elements upstream of the minimum liver‐type pyruvate kinase promoter‐directed insulin gene. Then, we have differentiated these transfected cells to hepatocyte‐like cells by using serial exposure of different inducing material and exogenous growth factors. Immunofluorescence analyses have demonstrated the expression of albumin, cytokeratin‐18, Hep‐Par1, α‐fetoprotein, and insulin. The expression of hepatocyte marker genes in the differentiated cells was confirmed by reverse‐transcription polymerase chain reaction. Interestingly, flow cytometry results showed that approximately 60% of the insulin‐producing hepatocyte‐like cells were simultaneously cytochrome P450 3A4 (CYP3A4) and insulin positive. CYP3A4 is a significant enzyme found in mature liver tissue. This confirmed that the differentiation and the transfection procedures were done correctly. They were functionally active by releasing insulin in response to elevated glucose concentrations in vitro. These applicable cells could be used in the liver for cell therapy of diabetes.
Combined Effect of Diosgenin Along with Ezetimibe or Atorvastatin on the Fate of Labelled Bile Acid and Cholesterol in Hypercholesterolemic Rats

We analyzed the effect of diosgenin, administered with atorvastatin or ezetimibe, on the fate of 3H(G)-taurocholic acid or 26-14C-cholesterol in hypercholesterolemic rats. Male Wistar rats received a hypercholesterolemic diet (HD), HD + atorvastatin (HD+ATV), HD + ezetimibe (HD+EZT), HD + diosgenin (HD+DG), HD+ATV+EZT, or HD+ATV+DG for 40 days. We also included a control normal group (ND). The labelled compounds were administered on day 30. The animals were placed in metabolic cages for daily feces collection. At day 40 the rats were sacrificed. Lipid extracts from blood, liver, spinal cord, testicles, kidneys, epididymis, intestine, and feces were analyzed for radioactivity. Cholesterol activity was the highest in the liver in HD rats. DG diminished one half of this activity in HD+DG and HD+ATV+DG groups in comparison with the HD group. HD+ATV rats showed four to almost ten-fold cholesterol activity in the spinal cord compared with the ND or HD rats. Fecal elimination of neutral steroids was approximately two-fold higher in the HD+DG and HD+ATV+DG groups. Taurocholic acid activity was four to ten-fold higher in HD+DG intestine as compared to the other experimental groups. Taurocholic activity in the liver of HD and HD+DG groups was two and a half higher than in ND. Our results show that the combination of DG and ATV induced the highest cholesterol reduction in the liver and other tissues.
Monosodium glutamate daily oral supplementation: study of its effects on male reproductive system on rat model

ABSTRACT Monosodium glutamate (MSG) is widely used in food preparation industry and has been consumed regularly. Previous studies had reported on effects of MSG when given at extremely high dosages, the results are not applicable to human equivalent intake. Therefore, the present study aimed to evaluate the effect of MSG on sperm quality and changes in reproductive organs of adult male rats when taken at average human daily intake (ADI). Twenty-four adult male rats were randomly assigned into three groups; NC (Normal control), MSG60 and MSG120 where MSG was given orally at 60 mg/kg and 120 mg/kg to each respective group. All treatments were conducted for 28 consecutive days. MSG at estimated ADI of 120 mg/kg body weight resulted in a significant drop in sperm quality (p < 0.05) when compared to both control and MSG60 groups. A significant decrease in the weight of reproductive organs was also apparent (p < 0.05). Moreover, oxidative status evaluation showed that treatment of MSG induces oxidative stress in the testis, more severely at a dose of 120 mg/kg body weight. These findings are supported by alterations in the observed histology of reproductive organs. This study shows that an intake dose of 120 mg/kg body weight MSG could cause significant damage to the reproductive system. Abbreviations: MSG: Monosodium glutamate; ADI: average daily intake; PUFA: polyunsaturated fatty acid; FSH: follicle stimulating hormone; LH: luteinizing hormone; TCA: tricarbocylic acid; PF: prostatic fluid
IMMUNE MEDIATED DISEASES IN PATIENTS WITH CELIAC DISEASE AND THEIR RELATIVES: A COMPARATIVE STUDY OF AGE AND SEX.

BACKGROUND Up to 15% of other immune-mediated diseases (IMDs) can occur in patients with CD throughout their lives and are associated with multiple factors, including sex and sex hormone levels. Moreover, sex is associated with differences in clinical presentation, onset, progression, and outcomes of disorders. OBJECTIVE To investigate the prevalence of IMDs at diagnosis in patients with celiac disease (CD) and their first-degree relatives and to compare the findings between female and male patients of different age. METHODS A retrospective study including Brazilian patients with CD who visited the same doctor during January 2012 to January 2017 was performed. Demographic and medical history data were collected through self-administered questionnaires and medical charts of the patients. In total, 213 patients were examined at diagnosis: 52 males (mean age, 40.0 years) and 161 females (mean age, 41.4 years). The patients were divided into two groups according to sex and age. RESULTS IMDs were observed in 60.2% of the female (97/161) and 42.3% of the male patients (22/52; P=0.22). However, the frequency of IMDs was significantly higher in females aged 51-60 years than in males with same age (P=0.0002). Dermatitis herpetiformis (DH) was significantly more prevalent in males (P=0.02), whereas atopy was more prevalent in females (P=0.02). IMDs observed in first-degree relatives were similar to those observed in patients (70.9%; P<0.001), with a higher number observed in female relatives. CONCLUSION The frequency of IMDs in CD patients was similar in all age groups and both sexes, except women diagnosed with CD after 51 years of age presented with an increased frequency of IMDs compared with males. Dermatitis herpetiformis was more prevalent in males, whereas atopy was more prevalent in females. No difference was observed in the type of IMDs between the first-degree relatives of both sexes.
Myeloid Cells during Viral Infections and Inflammation

Myeloid cells represent a diverse range of innate leukocytes that are crucial for mounting successful immune responses against viruses. These cells are responsible for detecting pathogen-associated molecular patterns, thereby initiating a signaling cascade that results in the production of cytokines such as interferons to mitigate infections. The aim of this review is to outline recent advances in our knowledge of the roles that neutrophils and inflammatory monocytes play in initiating and coordinating host responses against viral infections. A focus is placed on myeloid cell development, trafficking and antiviral mechanisms. Although known for promoting inflammation, there is a growing body of literature which demonstrates that myeloid cells can also play critical regulatory or immunosuppressive roles, especially following the elimination of viruses. Additionally, the ability of myeloid cells to control other innate and adaptive leukocytes during viral infections situates these cells as key, yet under-appreciated mediators of pathogenic inflammation that can sometimes trigger cytokine storms. The information presented here should assist researchers in integrating myeloid cell biology into the design of novel and more effective virus-targeted therapies.
Dabigatran dual therapy with ticagrelor or clopidogrel after percutaneous coronary intervention in atrial fibrillation patients with or without acute coronary syndrome: a subgroup analysis from the RE-DUAL PCI trial

Abstract Aims After percutaneous coronary intervention (PCI) in patients with atrial fibrillation, safety and efficacy with dabigatran dual therapy were evaluated in pre-specified subgroups of patients undergoing PCI due to acute coronary syndrome (ACS) or elective PCI, and those receiving ticagrelor or clopidogrel treatment. Methods and results In the RE-DUAL PCI trial, 2725 patients were randomized to dabigatran 110 mg or 150 mg with P2Y12 inhibitor, or warfarin with P2Y12 inhibitor and aspirin. Mean follow-up was 14 months, 50.5% had ACS, and 12% received ticagrelor. The risk of the primary endpoint, major or clinically relevant non-major bleeding event, was reduced with both dabigatran dual therapies vs. warfarin triple therapy in patients with ACS [hazard ratio (95% confidence interval), 0.47 (0.35–0.63) for 110 mg and 0.67 (0.50–0.90) for 150 mg]; elective PCI [0.57 (0.43–0.76) for 110 mg and 0.76 (0.56–1.03) for 150 mg]; receiving ticagrelor [0.46 (0.28–0.76) for 110 mg and 0.59 (0.34–1.04) for 150 mg]; or clopidogrel [0.51 (0.41–0.64) for 110 mg and 0.73 (0.58–0.91) for 150 mg], all interaction P-values >0.10. Overall, dabigatran dual therapy was comparable to warfarin triple therapy for the composite endpoint of death, myocardial infarction, stroke, systemic embolism, or unplanned revascularization, with minor variations across the subgroups, all interaction P-values >0.10. Conclusion The benefits of both dabigatran 110 mg and 150 mg dual therapy compared with warfarin triple therapy in reducing bleeding risks were consistent across subgroups of patients with or without ACS, and patients treated with ticagrelor or clopidogrel.
Matrix Metalloproteinase‐1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity

Rationale: Matrix metalloproteinase‐1 (MMP‐1) and mast cells are present in the airways of people with asthma. Objectives: To investigate whether MMP‐1 could be activated by mast cells and increase asthma severity. Methods: Patients with stable asthma and healthy control subjects underwent spirometry, methacholine challenge, and bronchoscopy, and their airway smooth muscle cells were grown in culture. A second asthma group and control subjects had symptom scores, spirometry, and bronchoalveolar lavage before and after rhinovirus‐induced asthma exacerbations. Extracellular matrix was prepared from decellularized airway smooth muscle cultures. MMP‐1 protein and activity were assessed. Measurements and Main Results: Airway smooth muscle cells generated pro‐MMP‐1, which was proteolytically activated by mast cell tryptase. Airway smooth muscle treated with activated mast cell supernatants produced extracellular matrix, which enhanced subsequent airway smooth muscle growth by 1.5‐fold (P < 0.05), which was dependent on MMP‐1 activation. In asthma, airway pro‐MMP‐1 was 5.4‐fold higher than control subjects (P = 0.002). Mast cell numbers were associated with airway smooth muscle proliferation and MMP‐1 protein associated with bronchial hyperresponsiveness. During exacerbations, MMP‐1 activity increased and was associated with fall in FEV1 and worsening asthma symptoms. Conclusions: MMP‐1 is activated by mast cell tryptase resulting in a proproliferative extracellular matrix. In asthma, mast cells are associated with airway smooth muscle growth, MMP‐1 levels are associated with bronchial hyperresponsiveness, and MMP‐1 activation are associated with exacerbation severity. Our findings suggest that airway smooth muscle/mast cell interactions contribute to asthma severity by transiently increasing MMP activation, airway smooth muscle growth, and airway responsiveness.
Proteomic analysis of synovial fluid: current and potential uses to improve clinical outcomes

ABSTRACT Introduction: Synovial fluid (SF) is in close proximity to tissues which are primarily altered during articular disease and has significant potential to better understand the underlying disease pathogeneses of articular pathologies and biomarker discovery. Although development of mass spectrometry-based methods has allowed faster and higher sensitivity techniques, interrogation of the SF proteome has been hindered by its large protein concentration dynamic range, impeding quantification of lower abundant proteins. Areas covered: Recent advances have developed methodologies to reduce the large protein concentration dynamic range of SF and subsequently allow deeper exploration of the SF proteome. This review concentrates on methods to overcome biofluid complexity, mass spectrometry proteomics methodologies, extracellular vesicles proteomics and the application of advances within the field in clinical disease, including osteoarthritis, rheumatoid arthritis, spondyloarthritis and juvenile arthritis. A narrative review was conducted with articles searched using PubMed, 1991–2018. Expert opinion: The SF proteomics field faces various challenges, including the requirement for rigorous and standardised methods of sample collection/storage, the sensitivity and specificity of proteomic assays, techniques to combat the large protein concentration dynamic range and comprehensive data analysis to reduce falsely identified markers. Additionally, there are challenges in developing multi ‘omic’ integration techniques, with computational integration enhancing analysis.