Internalized sexual stigma may hamper the development of self-identity, social interaction, and intimate relationship in lesbian, gay, and bisexual (LGB) individuals. The Measure of Internalized ...Sexual Stigma for Lesbians and Gay Men (MISS-LG) is an important instrument assessing internalized sexual stigma for LGB individuals. However, its psychometric properties have not been examined in LGB populations outside the Italian community. The present study used advanced psychometric testing to evaluate the traditional Chinese version (the MISS-LG) among LGB individuals in Taiwan. LGB individuals (500 male, 500 female) participated in this study and completed the MISS-LG, HIV and Homosexuality Related Stigma (HHRS), and Acceptance and Action Questionnaire-II (AAQ). Confirmatory factor analysis results confirmed the three-factor structure of the MISS-LG; however, two items for males and one item for females had somewhat low factor loadings on the sexuality factor. Each MISS-LG factor was found to be unidimensional in Rasch results, except for the slight misfit in Item 3 and concurrent validity of the MISS-LG was supported by the positive correlations with HHRS and the AAQ. The Chinese MISS-LG has relatively satisfactory psychometric properties. However, further research is needed to investigate the reasons for problematic fitting of several items.
Abstract
High-entropy alloys consisting of CoCrFeNiAl as the major elements and 2–5 at% Mn as the minor element were prepared using a vacuum arc melting method. The crystalline structures of the ...prepared alloys were identified by x-ray diffraction. Moreover, the mechanical properties of the alloys were examined under quasi-static (10
−1
, 10
−2
and 10
−3
s
−1
) and dynamic (3000, 4000, and 5000 s
−1
) loading conditions using a universal testing machine and split-Hopkinson pressure bar system, respectively. The experimental results showed that, for all of the HEA alloys, the flow stress and strain rate sensitivity coefficient increased with increasing strain rate. Among all the alloys, that with 3 at% Mn exhibited the best mechanical properties. A significant loss in plasticity was observed as the Mn content increased to 5 at%. The scanning electron microscope observations showed that the favorable mechanical properties of the alloy with 3 at% Mn were the result of a compact dimple structure, which enhanced the toughness. The HEA with 5 at% Mn showed the best electrochemical corrosion resistance among all the alloys due to the formation of dendritic structures at the grain boundaries.
Background:
High-performance liquid chromatography–tandem mass spectrometry (HPLC-TMS) is preferred to fluorescent polarisation immunoassay (FPIA) in therapeutic drug monitoring (TDM), as it only ...measures active drug. Our hospital replaced FPIA with HPLC-TMS for analysis of calcineurin inhibitor (CNI) levels. Preliminary studies demonstrated significantly lower CNI levels with HPLC-TMS versus FPIA in kidney transplant recipients (KTRs). Most studies evaluating CNI exposure in KTRs used FPIA, posing challenges in interpreting HPLC-TMS levels. This study aimed to compare the effectiveness and safety outcomes in the one-year period before (FPIA period) and after (HPLC-TMS period) the switch.
Methods:
A retrospective cohort study was conducted on KTRs receiving ciclosporin (CsA) or tacrolimus (FK). Primary effectiveness end points were biopsy-proven acute rejection (BPAR) rate and estimated glomerular filtration rate (eGFR); safety end points were viral infections and hospitalisation for infection. The secondary end point was change in CNI levels during the FPIA versus HPLC-TMS periods.
Results:
A total of 307 patients were analysed (CsA n=182, FK n=125). BPAR only occurred in two patients in the HPLC-TMS period among the CsA cohort (p=0.50), but it occurred in six patients in the FPIA period and one patient in the HPLC-TMS period (p=0.13) among the FK cohort. Median eGFR were similar in both periods (CsA: 52.2 mL/min/1.73 m2 (interquartile range (IQR) 39.8–67.6) vs. 52.5 mL/min/1.73 m2 (IQR 37.1–68.0), p=0.65; FK: 57.7 mL/min/1.73 m2 (IQR 39.1–80.0) vs. 56.4 mL/min/1.73 m2 (IQR 33.5–76.7), p=0.08). There were no significant differences in safety outcomes. The median change in CNI levels from the FPIA period to the HPLC-TMS period was –20.5% (IQR –32.5 to –3.9) and –6.9% (IQR –17.7 to 8.0) among CsA and FK cohorts, respectively (p<0.01).
Conclusion:
The switch from FPIA to HPLC-TMS for CNI TDM in KTRs did not yield significant changes in clinical end points.
Investigations into the association of antepartum maternal infections with the pathogenesis of biliary atresia (BA) in human offspring are insufficient.
To examine the association between prenatal ...infections in mothers and the development of BA in their offspring.
This population-based case-control study obtained administrative data from the Taiwan National Health Insurance Research Database with linkage to the Taiwan Maternal and Child Health Database, capturing demographic and medical information on nearly all 23 million of the Taiwan population. The cohort comprised 2 905 978 singleton live births among mother-infant dyads between January 1, 2004, and December 31, 2020, in Taiwan. The case group of infants with BA was identified from use of International Classification of Diseases diagnostic codes for BA and subsequent Kasai procedure or liver transplant. The control group was randomly selected from infants without BA, representing approximately 1 in 1000 study population. Data analyses were performed from May 1 to October 31, 2023.
Prenatal maternal infections, including intestinal infection, influenza, upper airway infection, pneumonia, soft-tissue infection, and genitourinary tract infection.
The main outcome was exposure to prenatal maternal infections. Inverse probability weighting analysis was performed by building a logistic regression model to estimate the probability of the exposure observed for a particular infant and using the estimated probability as a weight in subsequent analyses. The weighted odds ratio (OR) estimated by logistic regressions was then used to assess the risk of BA in offspring after prenatal maternal infections.
Among the mother-infant dyads included, 447 infants with BA were cases (232 females 51.9%) and 2912 infants without BA were controls (1514 males 52.0%). The mean (SD) maternal age at childbirth was 30.7 (4.9) years. Offspring exposed to prenatal intestinal infection (weighted OR, 1.46; 95% CI, 1.17-1.82) and genitourinary tract infection (weighted OR, 1.22; 95% CI, 1.05-1.41) in mothers exhibited a significantly higher risk of BA. Furthermore, maternal intestinal infection (weighted OR, 6.05; 95% CI, 3.80-9.63) and genitourinary tract infection (weighted OR, 1.55; 95% CI, 1.13-2.11) that occurred during the third trimester were associated with an increased risk of BA in offspring.
Results of this case-control study indicate an association between prenatal intestinal infection and genitourinary tract infection in mothers and BA occurrence in their offspring. Further studies are warranted to explore the underlying mechanisms of this association.
Acute hepatopancreatic necrosis disease (AHPND) is a severe, newly emergent penaeid shrimp disease caused by Vibrio parahaemolyticus that has already led to tremendous losses in the cultured shrimp ...industry. Until now, its disease-causing mechanism has remained unclear. Here we show that an AHPND-causing strain of V. parahaemolyticus contains a 70-kbp plasmid (pVA1) with a postsegregational killing system, and that the ability to cause disease is abolished by the natural absence or experimental deletion of the plasmid-encoded homologs of the Photorhabdus insect-related (Pir) toxins PirA and PirB. We determined the crystal structure of the V. parahaemolyticus PirA and PirB (PirA(vp) and PirB(vp)) proteins and found that the overall structural topology of PirA(vp)/PirB(vp) is very similar to that of the Bacillus Cry insecticidal toxin-like proteins, despite the low sequence identity (<10%). This structural similarity suggests that the putative PirAB(vp) heterodimer might emulate the functional domains of the Cry protein, and in particular its pore-forming activity. The gene organization of pVA1 further suggested that pirAB(vp) may be lost or acquired by horizontal gene transfer via transposition or homologous recombination.
Abstract
Pulmonary fibrosis (PF) is a major public health problem with limited therapeutic options. There is a clear need to identify novel mediators of PF to develop effective therapeutics. Here we ...show that an ER protein disulfide isomerase, thioredoxin domain containing 5 (TXNDC5), is highly upregulated in the lung tissues from both patients with idiopathic pulmonary fibrosis and a mouse model of bleomycin (BLM)-induced PF. Global deletion of
Txndc5
markedly reduces the extent of PF and preserves lung function in mice following BLM treatment. Mechanistic investigations demonstrate that TXNDC5 promotes fibrogenesis by enhancing TGFβ1 signaling through direct binding with and stabilization of TGFBR1 in lung fibroblasts. Moreover, TGFβ1 stimulation is shown to upregulate TXNDC5 via ER stress/ATF6-dependent transcriptional control in lung fibroblasts. Inducing fibroblast-specific deletion of
Txndc5
mitigates the progression of BLM-induced PF and lung function deterioration. Targeting TXNDC5, therefore, could be a novel therapeutic approach against PF.
Head and neck cancer (HNC) is one of the 10 most frequent cancers worldwide, with an estimated over 500 000 new cases being diagnosed annually. The overall 5‐year survival rate in patients with HNC ...is one of the lowest among common malignant neoplasms and has not significantly changed during the last two decades. Oral cavity squamous cell carcinoma (OSCC) shares part of HNC and has been reported to be increasing in the betel quid chewing area in recent years. During 2006, OSCC has become the sixth most common type of cancer in Taiwan, and it is also the fourth most common type of cancer among men. It follows that this type of cancer wreaks a high social and personal cost. Environmental carcinogens such as betel quid chewing, tobacco smoking and alcohol drinking have been identified as major risk factors for head and neck cancer. There is growing interest in understanding the relationship between genetic susceptibility and the prevalent environmental carcinogens for HNC prevention. Within this review, we discuss the molecular and cellular aspects of HNC carcinogenesis in Taiwan, an endemic betel quid chewing area. Knowledge of molecular carcinogenesis of HNC may provide critical clues for diagnosis, prognosis, individualization of therapy and molecular therapeutics. (Cancer Sci 2008; 99: 1507–1514)
Background & Aims Patients with chronic hepatitis B virus (HBV) infection have a high risk for developing hepatocellular carcinoma (HCC). Patients with lower levels of hepatitis B surface antigen ...(HBsAg) have higher chances of losing HBsAg than those with high levels. However, little is known about whether higher levels of HBsAg increase risk for HCC. Methods We followed 2688 Taiwanese HBsAg-positive patients without evidence of cirrhosis for a mean time period of 14.7 years. In addition to the known risk factors of HCC, we investigated the association between levels of HBsAg and development of HCC. Results Of the patients followed, 191 developed HCC, with an average annual incidence rate of 0.5%. Baseline levels of HBsAg and HBV were associated with development of HCC, and risk increased with level. Compared to HBsAg level, by receiver operating characteristic curve analysis, HBV DNA level better predicted the development of HCC during 10-year and 15-year periods (both, P < .001). However, when we evaluated hepatitis B e antigen−negative patients with levels of HBV DNA <2000 IU/mL, factors that determined HCC risk included sex, age, and levels of alanine aminotransferase and HBsAg (≥1000 IU/mL), but not level of HBV DNA. Multivariate analysis showed that the adjusted hazard ratio for HCC in patients with levels of HBsAg ≥1000 IU/mL versus <1000 IU/mL was 13.7 (95% confidence interval: 4.8−39.3). Conclusions Among patients infected with HBV genotype B or C, determinants of HCC risk include their sex, age, hepatitis B e antigen status, HBV genotype, and levels of alanine aminotransferase and HBV DNA, but not level of HBsAg. Among hepatitis B e antigen−negative patients with low viral loads, HCC risk is determined by levels of HBsAg and alanine aminotransferase and age, but not HBV DNA.
The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) afatinib improves survival in nonsmall cell lung cancer (NSCLC) patients with EGFR mutation. We analysed the outcome between ...EGFR mutation subtypes in a large afatinib‐treated cohort in which 516 EGFR‐mutated NSCLC patients receiving afatinib as front‐line treatment. EGFR uncommon mutations include exon 20 insertion, de novo T790M of high or low allele frequency (dT790MHAF/dT790MLAF), non‐T790M compound mutation and others, where EGFR exon 20 insertion and dT790MHAF were defined as type‐I and the rest as type‐II uncommon mutation. Four hundred and sixty‐one (89.3%) and 55 (10.7%) patients were common and uncommon mutation, respectively. Exon 20 insertion and dT790MHAF patients demonstrated a significantly shortened progression‐free survival (PFS) (2.6 and 4.1 months) compared to EGFR common mutation, dT790MLAF and other uncommon mutation patients (15.1, 27.0 and 18.4 months; P = 3 × 10−8). Type‐I uncommon mutation was an independent predictor of PFS (HR 4.46 95% CI, 2.60‐7.64; P < .001) and OS (HR 2.56 95% CI, 1.37‐4.75; P = .003). EGFR L858R patients demonstrated a significantly higher CNS progression (cause‐specific HR, 3.16; 95% CI 1.24‐8.08; P = .016), and type‐I uncommon mutation patients exhibited a significantly higher systemic progression (cause‐specific HR, 4.95; 95% CI 2.30‐10.60; P = 4.3 × 10−5). Tendencies of higher CNS and lower systemic progression were observed in type‐II uncommon mutation patients. A PFS ≥ 12 months (OR 2.38 95% CI, 1.18‐4.89; P = .016) and uncommon EGFR mutation (OR 0.08 95% CI, 0.01‐0.48; P = .021) were independent predictors of secondary T790M. Afatinib‐treated NSCLC patients presented an EGFR genotype‐specific pattern of disease progression and outcome.
What's new?
For patients with nonsmall cell lung cancer (NSCLC), epidermal growth factor tyrosine kinase inhibitors (EGFR‐TKIs) can significantly improve survival. EGFG‐TKI effectiveness, however, is compromised by acquired EGFR mutations, especially de novo T790M mutations. Here, the impact of EGFR genotypes on the efficacy of afatinib, a second‐generation EGFR‐TKI, was investigated in a cohort of EGFR‐mutated NSCLC patients. Afatinib efficacy was associated with T790M allele quantity in patients with de novo T790M mutation. In particular, front‐line afatinib therapy was associated with favourable survival in EGFR‐mutated patients, whereas resistance was marked by a genotype‐specific pattern of disease progression, with secondary T790M development.
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