Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationship of the aquaporin-5 gene polymorphism with chronic obstructive pulmonary disease in Han population of north China

Objective To explore the relationship between aquaporin-5 (AQP5) gene polymorphism and the genetic susceptibility and clinical severity of chronic obstructive pulmonary disease (COPD) in Han population of north China. Methods Two hundred and twenty COPD patients (142 males and 78 females, aged 37-101 (74.0±10.0) years, diagnosed in the 306 Hospital of PLA from Jun. 2007 to May 2012) were listed as the study group, and 285 healthy subjects (183 males and 102 females, aged 44¬97 (72.5±8.6) years) were recruited as control group. The COPD patients with FEV1/FVC <70% were divided into 4 subgroups based on Post-Bronchodiflator FEV1: those with FEV1% ≥80% were assigned as mild subgroup, patients with 50% ≤FEV1% <80% as in moderate subgroup, with 30% ≤FEV1% <50% as severe subgroup, and those with FEV1% ≤30% as very severe subgroup. Patients in mild and moderate subgroups were combined into mild-to-moderate group, and those in severe and very severe subgroups were combined into severe-to-very severe group. Three tSNPs (rs3736309, rs296754 and rs296759) of AQP5 gene were selected for genotyping by PCR-RFLP and SNaPshot analysis. Chi-square test was used to perform the Hardy-Weinberg test, and unconditional logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI). The genotype frequency distribution was compared to identify relationship between AQP5 gene polymorphisms and COPD in Han population of north China. The genotype frequency distribution between mild-to-moderate and severe-to-very severe group was compared to further clarify the relationship between AQP5 gene polymorphisms and the severity of COPD. Results The genotype distribution of 3 tSNPs in COPD patients showed no difference from that in healthy controls. Advanced analysis performed in the COPD patients revealed that the genotype distribution of rs3736309 in mild-to-moderate COPD patients was significantly different to that in severe-to¬very severe patients (P<0.05). The genotypes rs296754 and rs296759 were not associated with severity of airway obstruction. Conclusion The AQP5 polymorphism is not associated with the incidence of COPD, but associated with a high risk of developing severe of COPD.
Rapid Declines in Age Group-Specific Rotavirus Infection and Acute Gastroenteritis Among Vaccinated and Unvaccinated Individuals Within 1 Year of Rotavirus Vaccine Introduction in England and Wales.

BACKGROUND The oral infant rotavirus vaccine, Rotarix, was introduced in England and Wales in July 2013. We estimated the impact on laboratory-confirmed rotavirus infections and hospitalizations for all-cause acute gastroenteritis (AGE) during the first year after introduction. METHODS We extracted data on laboratory-confirmed rotavirus infections (July 2000 through June 2015) and all-cause AGE-associated hospitalizations (July 2007 through June 2014) for all age groups using national databases (LabBase2 and HES). We determined the ratio of the rate during the 2013-2014 rotavirus season to the rate during the prevaccination era. RESULTS In infants, there was a 77% decline (rate ratio [RR], 0.23; 95% confidence interval [CI], .16-.32) in laboratory-confirmed rotavirus infections and a 26% decline (RR, 0.74; 95% CI, .65-.84) in all-cause AGE-associated hospitalizations in 2013-2014, compared with the prevaccination era. Large reductions were also observed in older children, adults, and older adults. We estimated that 10 884 laboratory-confirmed infections and 50 427 all-cause AGE-associated hospital admissions were averted in 2013-2014. Similar reductions have been observed for laboratory-confirmed rotavirus infections during the 2014-2015 season. CONCLUSIONS The rapid declines in rotavirus infection and AGE in vaccinated and unvaccinated age groups within 1 year of introducing an infant rotavirus vaccination program are far greater than expected and than previously reported by other countries.
Hereditäre Erkrankungen mit Gelenkhypermobilität

Zusammenfassung Unter Gelenkhypermobilität versteht man die Überbeweglichkeit eines oder mehrerer Gelenke. Hypermobilität ist oftmals mit extraartikulären Begleitmanifestationen vergesellschaftet und tritt gehäuft bei hereditären Erkrankungen des Bindegewebes und Skeletts, wie Marfan-Syndrom (MFS), marfanoiden Erkrankungen, Ehlers-Danlos-Syndrom (EDS), Osteogenesis imperfecta (OI) und weiteren Skelettdysplasien auf. Während das MFS durch Fibrillin-1 (FBN1)-Mutationen hervorgerufen wird, führen Mutationen in den TGFbeta-Rezeptoren TGFBR1 und TGFBR2 zum marfanähnlichen Loeys-Dietz-Syndrom (LDS). Untersuchungen an Mausmodellen und bei Patienten zeigen, dass eine erhöhte Verfügbarkeit von Transforming-Growth- Factor (TGF)-beta ein wichtiger Faktor bei der Pathogenese des MFS und LDS ist. Demgegenüber werden die unterschiedlichen EDS- und OI-Formen durch Mutationen verursacht, die die Synthese und Modifikation verschiedener fibrillärer Kollagene betreffen. In diesem Übersichtsartikel präsentieren wir eine aktuelle Zusammenfassung bedeutsamer klinischer und genetischer Erkenntnisse von hereditären Erkrankungen des Bindegewebes und Skeletts mit Gelenkhypermobilität.
Identification of Targetable ERBB2 Aberrations in Head and Neck Squamous Cell Carcinoma.

IMPORTANCE ERBB2 (formerly HER2) is an important drug target in breast cancer, where anti-ERBB2 therapy has been shown to lead to improvements in disease recurrence and overall survival. ERBB2 status in head and neck squamous cell carcinoma (HNSCC) has not been well studied. Identification of ERBB2-positive tumors and characterization of response to ERBB2 therapy could lead to targeted treatment options in HNSCC. OBJECTIVE To identify ERBB2 aberrations in HNSCCs and investigate the potential for ERBB2-targeted therapy in HNSCCs. DESIGN, SETTING, AND PARTICIPANTS A retrospective case series of patients with laryngeal (42 tumor specimens) and oral cavity (94 tumor specimens) SCC enrolled in the University of Michigan Head and Neck Specialized Program of Research Excellence was conducted. Publicly available sequencing data (The Cancer Genome Atlas), as well as data from other studies, were reviewed to identify additional mutations and overexpression in ERBB2 in HNSCC. Established HNSCC cell lines were used for follow-up in vitro analysis. The study was conducted from October 1, 2014, to August 30, 2015. INTERVENTIONS With the use of targeted, amplicon-based sequencing with the Oncomine Cancer Panel, the copy number and mutation status of commonly altered genes in HNSCCs were assessed. Immunohistochemical staining was performed on tissue microarrays of HNSCCs to assess the expression of ERBB2. Western blotting for HNSCC cell line ERBB2 expression and cell survival assays after treatment with ERBB2 inhibitors were performed. MAIN OUTCOMES AND MEASURES The prevalence of ERBB2 genetic aberrations and ERBB2 overexpression in laryngeal and oral cavity SCCs, prevalence of ERBB2 aberrations in HNSCC in The Cancer Genome Atlas, ERBB2 protein expression in HNSCC cell lines, and response of HNSCC cell lines to targeted ERBB2 inhibitors. RESULTS Of the 42 laryngeal SCC samples screened by targeted sequencing, 4 (10%) were positive for ERBB2 amplification. Two of these samples showed ERBB2 overexpression on immunohistochemistry. Two of the 94 oral cavity SCC samples (2%) were positive for ERBB2 on immunohistochemistry. Analysis of 288 patients from publicly available HNSCC sequencing data revealed 9 amplifications (3%) in ERBB2. Protein expression was variable across HNSCC cell lines, and a subset of these cell lines showed responsiveness to anti-ERBB2 therapy. CONCLUSIONS AND RELEVANCE ERBB2 aberrations were identified in a subset of HNSCCs. These tumors may be responsive to targeted therapy against ERBB2. Screening for ERBB2 aberrations and applying targeted therapy in ERBB2-positive patients may be useful in personalized therapy trials, particularly in patients who are refractory to current treatment paradigms.
Mujer con anemia y pruebas de función hepática anormales

Se trata de una mujer de 45 años de edad, sin antecedentes de importancia. Acude a la consulta de gastroenterología referida del servicio de hematología donde era evaluada por síndrome anémico: astenia, adinamia, palidez de tegumentos, de un año de evolución; en su primera consulta la paciente presentaba a la exploración física esplenomegalia y los siguientes resultados de laboratorio: anemia normocítica, normocrómica; pruebas de funcionamiento hepático(PFH) con transaminasas cuatro veces por arriba de lo normal e hiperglobulinemia (Cuadro 1). Además, ecografía abdominal con datos de hipertensión portal (ascitis y esplenomegalia).
Measles Virus Neutralizing Antibody Response, Cell-Mediated Immunity, and Immunoglobulin G Antibody Avidity Before and After Receipt of a Third Dose of Measles, Mumps, and Rubella Vaccine in Young Adults.

BACKGROUND Two doses of measles, mumps, and rubella (MMR) vaccine are 97% effective against measles, but waning antibody immunity to measles and failure of the 2-dose vaccine occur. We administered a third MMR dose (MMR3) to young adults and assessed immunogenicity over 1 year. METHODS Measles virus (MeV) neutralizing antibody concentrations, cell-mediated immunity (CMI), and immunoglobulin G (IgG) antibody avidity were assessed at baseline and 1 month and 1 year after MMR3 receipt. RESULTS Of 662 subjects at baseline, 1 (0.2%) was seronegative for MeV-neutralizing antibodies (level, <8 mIU/mL), and 23 (3.5%) had low antibody levels (8-120 mIU/mL). One month after MMR3 receipt, 1 subject (0.2%) was seronegative, and 6 (0.9%) had low neutralizing antibodies, with only 21 of 662 (3.2%) showing a ≥ 4-fold rise in neutralizing antibodies. One year after MMR3 receipt, no subject was seronegative, and 10 of 617 (1.6%) had low neutralizing antibody levels. CMI analyses showed low levels of spot-forming cells after stimulation, suggesting the presence of T-cell memory, but the response was minimal after MMR3 receipt. MeV IgG avidity did not correlate with findings of neutralization analyses. CONCLUSIONS Most subjects were seropositive before MMR3 receipt, and very few had a secondary immune response after MMR3 receipt. Similarly, CMI and avidity analyses showed minimal qualitative improvements in immune response after MMR3 receipt. We did not find compelling data to support a routine third dose of MMR vaccine.
THE ROLE OF SOCIO-ECONOMIC INDICATORS IN THE CAUSATION OF CORONARY ARTERY DISEASE

South Asian countries have a high prevalence of coronary heart disease (CAD) in line with their economic development. In these countries, we find nearly one quarter of the total world population in the process of nutritional transition, from poverty to affluence due to rapid economic development. India; in particular, with a population of over one billion has a high burden of CAD. To evaluate the role of socio-economic and demographic variables on the coronary artery disease. A hospital based case-control study was conducted to investigate the role of social related risk factors on coronary artery disease (CAD) in an urban area of East Delhi from April 2002 to December 2004. To obtain more validate comparisons, a control group also was selected from community of East Delhi. The tools of enquiry were a pre-tested and pre-coded questionnaire, physical examination and laboratory testes. A confidence level of 95% and study power of 80% were considered for the interpretation of possible significant findings. Sexwise stratified analysis was separately done for male and female subjects. Comparison of male cases with their counterparts in both control groups indicated that the majority of them had significantly a college education, higher monthly income, semi or full professional occupations and were living in families with size of more than 9. The similar results was found for female cases as that majority of them as compare to females in both control groups were literate, employed and belonging to families with income levels of more than RS.8000. In addition, belonging to religion other than Hindus was another significant variable that was accounted for as risk for getting CAD. Our findings indicate that both male and female cases belonging to high socio-economic classes had higher chance for getting CAD as compare to their counterparte.
Multifunctional human transcriptional coactivator protein PC4 is a substrate of Aurora kinases and activates the Aurora enzymes

Positive coactivator 4 (PC4), a human transcriptional coactivator, is involved in diverse processes like chromatin organization and transcription regulation. It is hyperphosphorylated during mitosis, with unknown significance. For the first time, we demonstrate the function of PC4 outside the nucleus upon nuclear envelope breakdown. A fraction of PC4 associates with Aurora A and Aurora B and undergoes phosphorylation, following which PC4 activates both Aurora A and B to sustain optimal kinase activity to maintain the phosphorylation gradient for the proper functioning of the mitotic machinery. This mitotic role is evident in PC4 knockdown cells where the defects are rescued only by the catalytically active Aurora kinases, but not the kinase‐dead mutants. Similarly, the PC4 phosphodeficient mutant failed to rescue such defects. Hence, our observations establish a novel mitotic function of PC4 that might be dependent on Aurora kinase‐mediated phosphorylation.
Demonstration of the Blood-Stage Plasmodium falciparum Controlled Human Malaria Infection Model to Assess Efficacy of the P. falciparum Apical Membrane Antigen 1 Vaccine, FMP2.1/AS01.

BACKGROUND Models of controlled human malaria infection (CHMI) initiated by mosquito bite have been widely used to assess efficacy of preerythrocytic vaccine candidates in small proof-of-concept phase 2a clinical trials. Efficacy testing of blood-stage malaria parasite vaccines, however, has generally relied on larger-scale phase 2b field trials in malaria-endemic populations. We report the use of a blood-stage P. falciparum CHMI model to assess blood-stage vaccine candidates, using their impact on the parasite multiplication rate (PMR) as the primary efficacy end point. METHODS Fifteen healthy United Kingdom adult volunteers were vaccinated with FMP2.1, a protein vaccine that is based on the 3D7 clone sequence of apical membrane antigen 1 (AMA1) and formulated in Adjuvant System 01 (AS01). Twelve vaccinees and 15 infectivity controls subsequently underwent blood-stage CHMI. Parasitemia was monitored by quantitative real-time polymerase chain reaction (PCR) analysis, and PMR was modeled from these data. RESULTS FMP2.1/AS01 elicited anti-AMA1 T-cell and serum antibody responses. Analysis of purified immunoglobulin G showed functional growth inhibitory activity against P. falciparum in vitro. There were no vaccine- or CHMI-related safety concerns. All volunteers developed blood-stage parasitemia, with no impact of the vaccine on PMR. CONCLUSIONS FMP2.1/AS01 demonstrated no efficacy after blood-stage CHMI. However, the model induced highly reproducible infection in all volunteers and will accelerate proof-of-concept testing of future blood-stage vaccine candidates. CLINICAL TRIALS REGISTRATION NCT02044198.
Diagnostic et prise en charge des néoplasies intraépithéliales vulvaires et des cancers invasifs de la vulve

OBJECTIVE Update on the diagnosis and management of vulvar intraepithelial neoplasia (VIN) and vulvar carcinoma. METHOD Review of the literature. RESULTS The classification of VIN is leaning towards the development of two distinct anatomoclinical models. VIN of the usual type and of a differentiated type. New forms of treatment of preinvasive lesions that are less traumatic and as efficient will have to be evaluated in the future such as immunomodulators and photodynamic therapy. The invasive carcinoma is generally rapidly symptomatic and visible; however, more than one third of patients are still diagnosed at an advanced stage. New therapeutic alternatives are being examined such as the sentinel lymph node in early stages and the preoperative radiochemotherapy in advanced stages. CONCLUSIONS VIN and vulvar cancer need specialized treatment which may be mutilating, despite the fact that therapeutic options are well defined today and tend towards less aggressive surgery.
Incidence of AIDS-Defining Opportunistic Infections in a Multicohort Analysis of HIV-infected Persons in the United States and Canada, 2000-2010.

BACKGROUND There are few recent data on the rates of AIDS-defining opportunistic infections (OIs) among human immunodeficiency virus (HIV)-infected patients in care in the United States and Canada. METHODS We studied HIV-infected participants in 16 cohorts in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) during 2000-2010. After excluding 16 737 (21%) with any AIDS-defining clinical events documented before NA-ACCORD enrollment, we analyzed incident OIs among the remaining 63 541 persons, most of whom received antiretroviral therapy during the observation. We calculated incidence rates per 100 person-years of observation (hereafter, "person-years") with 95% confidence intervals (CIs) for the first occurrence of any OI and select individual OIs during 2000-2003, 2004-2007, and 2008-2010. RESULTS A total of 63 541 persons contributed 261 573 person-years, of whom 5836 (9%) developed at least 1 OI. The incidence rate of any first OI decreased over the 3 observation periods, with 3.0 cases, 2.4 cases, and 1.5 cases per 100 person-years of observation during 2000-2003, 2004-2007, and 2008-2010, respectively (Ptrend<.001); the rates of most individual OIs decreased as well. During 2008-2010, the leading OIs included Pneumocystis jiroveci pneumonia, esophageal candidiasis, and disseminated Mycobacterium avium complex or Mycobacterium kansasii infection. CONCLUSIONS For HIV-infected persons in care during 2000-2010, rates of first OI were relatively low and generally declined over this time.
Duration of Dengue Viremia in Blood Donors and Relationships Between Donor Viremia, Infection Incidence and Clinical Case Reports During a Large Epidemic.

BACKGROUND Dengue viruses (DENV-1-4) pose a transfusion-transmission risk. This study estimated the dengue RNA detection period in asymptomatic blood donors and relationships between donor viremia and dengue incidence during a large epidemic. METHODS Donor samples from the 2012 dengue transmission season in Rio de Janeiro, Brazil, were tested for DENV RNA by a transcription-mediated amplification (TMA) assay, with DENV types and viral loads determined by polymerase chain reaction. Samples collected during the first and last weeks of enrollment were tested for DENV immunoglobulin (Ig) G and IgM to estimate incidence during the study period, which was analyzed relative to nucleic acid amplification technology (NAT) yield to estimate the duration of NAT-detectable viremia and compared with reported clinical dengue cases in Rio. RESULTS Samples from 16 241 donations were tested; 87 (0.54%) were confirmed as DENV-4 RNA positive. Dengue IgM-positive/IgG-positive reactivity increased from 2.8% to 8.8%, indicating a 6.2% incidence (95% confidence interval [CI], 3.2%-9.1%) during the study period. Based on these data, we estimated a 9.1-day period (95% CI, 4.4-13.9 days) of RNA detectable with TMA. With 100 475 reported cases of clinical dengue, 1 RNA-positive donation was identified per 800 DENV cases. CONCLUSIONS These parameters allow projections of dengue incidence from donor NAT yield data and vice versa, and suggest that viremic donations will be rare relative to clinical disease cases.
Enhanced Genetic Characterization of Influenza A(H3N2) Viruses and Vaccine Effectiveness by Genetic Group, 2014-2015.

BACKGROUND During the 2014-2015 US influenza season, expanded genetic characterization of circulating influenza A(H3N2) viruses was used to assess the impact of the genetic variability of influenza A(H3N2) viruses on influenza vaccine effectiveness (VE). METHODS A novel pyrosequencing assay was used to determine genetic group, based on hemagglutinin (HA) gene sequences, of influenza A(H3N2) viruses from patients enrolled at US Influenza Vaccine Effectiveness Network sites. VE was estimated using a test-negative design comparing vaccination among patients infected with influenza A(H3N2) viruses and uninfected patients. RESULTS Among 9710 enrollees, 1868 (19%) tested positive for influenza A(H3N2) virus; genetic characterization of 1397 viruses showed that 1134 (81%) belonged to 1 HA genetic group (3C.2a) of antigenically drifted influenza A(H3N2) viruses. Effectiveness of 2014-2015 influenza vaccination varied by influenza A(H3N2) virus genetic group from 1% (95% confidence interval [CI], -14% to 14%) against illness caused by antigenically drifted influenza A(H3N2) virus group 3C.2a viruses versus 44% (95% CI, 16%-63%) against illness caused by vaccine-like influenza A(H3N2) virus group 3C.3b viruses. CONCLUSIONS Effectiveness of 2014-2015 influenza vaccination varied by genetic group of influenza A(H3N2) virus. Changes in HA genes related to antigenic drift were associated with reduced VE.
Cytotoxic Plants: Potential Uses in Prevention and Treatment of Cancer

Cancer is a leading cause of death worldwide and accounted for 7.6 million deaths (around 13% of all deaths) in 2008. Deaths from cancer worldwide are projected to continue to rise to over 11 million in 2030. [(2011) World health statistics]. Heredity and environmental changes affect the susceptibility to cancer affection. More than 30% of cancer could be prevented by modifying or avoiding key risk factors, including: tobacco use, being overweight or obese, low fruit and vegetable intake, physical inactivity, alcohol use, sexually transmitted HPV-infection, urban air pollution, indoor smoke from household use of solid fuels. Plants have been used as a major source of remedies from the ancient time. The modern drug discovery and development is also dependent of medicinal plants (Saklani & Kutty, 2008). Using plants in the treatment of cancer has long history and dates back to ancient time. There are strong evidences about cancer preventing properties of various kinds of herbs used as food, fruit, spices, and vegetables (Dossus, 2008; Kruk, 2007; Moyad, 2004; Montesano, 2001; Lyman, 1992). Dietary habits especially those involving fruits and vegetables have served the great interest in developing various preventive measures that influence cancer risk (Wu, 2009; Kurahashi, 2009). Phytochemicals of varied chemical structures from fruits and vegetables have already been studied extensively for their potential anticancer or chemopreventive efficacy (Ramos, 2008). Being the rich sources of vitamins, minerals, and fiber without posing “any side effects” made fruits and vegetables the best choice to lowering cancer risk and also in maintaining good general health. The important role of plant derived compounds is undeniable. Paclitaxel (Wani et al., 1971), camptothecin (Wall, 1998), combrestatin (Cirla & Mann, 2003), epipodophyllotoxin (Canel et al., 2000) and Vinca alkaloids (vinblastine, vincristine) (Johnson et al., 1963) are some examples of herbal originated cancer treatments. These are also many other plant-derived compounds that are in clinical trials for cancers (Saklani & K. Kutty, 2008).