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These findings have led to advances in direct epigenetic biomarker testing of patient tissue or body fluid specimens, as well as quantitative analysis. Based on these findings, drug validation of some targets involved in the epigenetic mechanism of liver disease is gradually being carried out clinically.Introduction Treatment of unresectable or metastatic urothelial carcinoma (UC) has historically relied upon platinum-based chemotherapy and, more recently, immune checkpoint inhibitors. When tumors progress despite those therapies, remaining effective options are limited.Areas covered In this review, the authors review the advancement in genomic targets in UC, most notably fibroblast growth factor receptor (FGFR). FGFR has been identified as a target in UC as it is commonly genomically altered (activating mutations or fusions), and may be enriched in UC subtypes that are relatively resistant to immune checkpoint blockade. Erdafitinib, a potent and selective inhibitor of FGFRs, represents the first targeted therapy approved for the treatment of UC by virtue of a confirmed response rate of 40% in an open-label, single-armed phase II trial in molecularly selected tumors. The authors provide their expert opinion of its approval and place it in the context of the current and forthcoming treatment strategies for metastatic UC.Expert opinion The approval of erdafitinib provides clinicians with an important new treatment option for patients with metastatic UC and projects forward into an era of enhanced molecular precision in identifying effective therapies in UC.We investigated cancer survivors' interactions on an online breast cancer support forum, focusing on how the network structures of brokerage and closure relate to the types of support received and to the language used in posts. Data came through the extraction of 1,443 forum members' online networks. Automated linguistic analysis was carried out on the 27,248 threads these survivors made and the 336,151 replies they received. Survivors' brokerage and closure levels were positively correlated with the use of positive affective words in their posts, a linguistic marker of well-being. Different network positions fostered different types of support in the community. Specifically, people bridging unconnected users (the broker role) were more likely to receive informational support whereas people in closely knit groups (the closure role) were more likely to receive emotional support. Theoretical, methodological, and practical implications are examined.In psychological and educational measurement, it is often of interest to assess change in an individual. The current study expanded on previous research by introducing methods that can evaluate individual change on multiple latent traits measured on multiple occasions. Deoxycytidine price The four methods considered are the likelihood ratio test (LRT), the multivariate Wald test (MWT), the modified multivariate Wald test (MMWT), and the score test (ST). Simulation studies were conducted to examine the true positive rate (TPR) and the false positive rate (FPR) of the new methods under a conventional fixed-form test and a computerized adaptive test (CAT). Manipulated variables included the number of occasions, change magnitudes, patterns of change, and correlations between latent traits. Results revealed that, in terms of FPR, all methods except MWT had close adherence to the nominal significance level. Among the three methods, the LRT is recommended as it provided a balance between FPR and TPR. Larger change magnitude yielded higher TPR, regardless of the remaining factors. With the same test length, a CAT yielded higher TPR than a conventional test. Real-data examples are provided of identifying psychometrically significant change across two to four occasions using a multivariate adaptive self-report medical outcomes measure from hospitalized patients. The detection of significant change among the three methods agreed highly, and those patients identified as having significant change exhibited large profile differences, which provided support for the valid performance of the proposed methods.Objective Early menopause (EM), menopause aged less then 45 years, occurs spontaneously or secondary to medical treatments and is associated with multiple health impacts. A word cloud is an image where the word size reflects the frequency of use. We aimed to assess the perspectives of women with EM using a word cloud.Methods Women diagnosed with EM, recruited from clinics/community, completed a survey including the open-ended question 'What words do you associate with EM?'. Demographics and medical history were collected. Data analysis included descriptive statistics, identification of word themes/stems/synonyms, word frequency, and chi-square test. A word cloud was constructed from words used by two or more women using 'Wordle' (www.wordle.net).Results Responses were obtained from 190/263 participants. link2 The mean age was 54 ± 11 years, with EM diagnosed at age 38 ± 5 years. The cause of EM was unknown (30% of women), bilateral oophorectomy (27%), cancer therapy (25%), or autoimmune/genetic/metabolic (17%). The commonest words reported were hot flushes (36.8% of women), mood swings (20.5%), and infertility (16.8%), which varied with age and cause of EM. Few women reported neutral/positive words.Conclusion Most words that women associate with EM have negative connotations and refer to symptoms. A word cloud is a novel way to illustrate women's perspectives.Two new dammarane-type triterpenoids, notoginsenoside SY1 (1) and notoginsenoside SY2 (2), were isolated from the stems and leaves of Panax notoginseng. Their structures were elucidated to be 3β, 12β-dihydroxy-22, 23, 24, 25, 26, 27-hexanordammarane-20-one 3-O-β-D-xylopyranosyl-(1→2)-O-β-D-glucopyranosyl-(1→2)-O-β-D-glucopyranoside (1), 3β, 12β-dihydroxy-20S, 24 R-epoxydammar-25-ene 3-O-β-D-xylopyranosyl-(1→2)-O-β-D-glucopyranosyl-(1→2)-O-β-D-glucopyranoside (2) by IR, HRESIMS and NMR experiments.We investigated the effects of melatonin on rats with induced hypothyroidism during gestation as well as its effect on the development of the gonads of their offspring. Fifteen pregnant rats were divided into three groups GC, rats without induced hypothyroidism; GH, rats with induced hypothyroidism; GHM, rats with induced hypothyroidism plus melatonin. Hypothyroidism was induced by oral administration of 6-propyl-2-thiouracil and melatonin was applied subcutaneously. Treatments were performed during gestation and lactation. For the matrices, we evaluated the number of pups, body weight gain, ovarian weight, thyroid weight, organosomatic index, thyroid stimulating hormone (TSH) dose and thyroid morphometry. For the pups, weight gain, TSH, weight, morphometry of the gonads and organosomatic index were analyzed, as well as the cell proliferation index. TSH was elevated only in the matrices of GH animals. Melatonin prevented reduction of ovarian and thyroid weight, number of pups, follicular diameter and thyroid epithelial proportion of the matrices with hypothyroidism. The offspring of rats of the GH group exhibited less body weight gain, gonad and thyroid weight, and gonad cell proliferation index compared to the offspring born of rats of the GC and GHM groups. Melatonin prevented the effects of maternal hypothyroidism on the offspring of rats.Previous research has shown that manipulating the pitch of a face (tilting the face upward or downward) affects the perceived femininity, masculinity, attractiveness, and dominance of the given face. However, previous research has not considered the influence of direct eye gaze on dominance perceptions or the ambiguity surrounding the proposed social signals sent from a static face. The current research used 94 participants across two studies (women = 63%, age M = 31). link3 Stimuli varied in head pitch angle, eye gaze, and motion/static appearance. Participants rated the stimuli for levels of masculinity, femininity, attractiveness, and dominance. Both studies confirmed that pitching the face upward at incrementally increasing angles resulted in a linear increase in ratings of masculinity, physical dominance, and social dominance and a linear decrease in ratings of femininity, physical attractiveness, and behavioral allure. Study 2 showed that these effects can be dependent on either the perceived structural change of the face or the actual movement of the face, and these are different for each rating category. The perceived dimorphism, attractiveness, and dominance of a face will change dependent on the angle of pitch it is presented but also whether it is moving or not, where it is moving in space, and what direction it is moving.INTRODUCTION Approximately 10% to 15% of people affected by sickle cell disease (SCD) in the United States are Latino, many of whom are primary Spanish speakers. A key tool for self-reported outcome measures, the Pediatric QOL Inventory (PedsQL) SCD module, was not available in Spanish. Here, we assess the linguistic validity of a Spanish translation and compare perception of disease-specific and generic quality of life (QOL) in a sample of Latino and non-Latino children with SCD and their parents. METHOD Following forward and backward translation, Spanish-speaking child-parent dyads linguistically validated the translated instruments. Disease-specific and generic QOL perception of 28 child-parent dyads who participated in a clinical feasibility trial, HABIT (Hydroxyurea Adherence for Personal Best in Sickle Cell Disease), were compared by ethnicity. Data were analyzed by descriptive statistics, Mann-Whitney U test, absolute score differences, and minimal clinically important differences (MCID). RESULTS The translated questionnaire required no further language changes. QOL scores were higher for Latino children and parents compared with non-Latinos, with score differences exceeding MCIDs for total scores and the majority of subscale scores. CONCLUSION Spanish language PedsQL SCD instruments allow measurement of QOL in Spanish-speaking Latino children with SCD and their parents. Score differences for Latinos mostly exceeded MCIDs, suggesting that these differences are clinically meaningful. Confirmation of these findings is warranted.Research question Do live birth rates (LBRs) differ in frozen cycles of women who received single versus double embryo transfer?Design Retrospective cohort study including women who underwent their first frozen embryo transfer (FET) in a tertiary referral University Hospital between 2009-2014.Results 3601 patients were included in the analysis with 1936 (53.8%) having a single embryo transfer (SET) and 1665 (46.2%) having a double embryo transfer (DET). Overall, 657/3601 (18.24%) had a live birth. LBR were similar between SET and DET either for cleavage [100/757 (13.1%) versus 153/1032 (14.8%), p = .33] or blastocyst stage FET [256/1179 (21.7%) versus 148/633 (23.4%), p = .4). Ongoing pregnancy rates were comparable between DET and SET [316/1665 (18.9%) versus 359/1936 (18.5%)]. Multiple delivery rates were significantly higher in women with DET compared to SET [53/316 (16.7%) versus 7/359 (1.9%), p  less then  .001]. Multivariate logistic regression analysis allowing adjustment for relevant confounders showed that the number of embryos transferred in the frozen cycle was not related to LBR.

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