Mental health impact of multiple sexually minoritized and gender expansive stressors among LGBTQ+ young adults: a latent class analysis.

AIMS: In the United States, lesbian, gay, bisexual, transgender, queer, intersex, asexual and other sexually minoritized and gender expansive (LGBTQ+) young adults are at increased risk for experiencing mental health inequities, including anxiety, depression and psychological distress-related challenges associated with their sexual and gender identities. LGBTQ+ young adults may have unique experiences of sexual and gender minority-related vulnerability because of LGBTQ+-related minority stress and stressors, such as heterosexism, family rejection, identity concealment and internalized homophobia. Identifying and understanding specific LGBTQ+-related minority stress experiences and their complex roles in contributing to mental health burden among LGBTQ+ young adults could inform public health efforts to eliminate mental health inequities experienced by LGBTQ+ young adults. Therefore, this study sought to form empirically based risk profiles (i.e., latent classes) of LGBTQ+ young adults based on their experiences with familial heterosexist experiences, LGBTQ+-related family rejection, internalized LGBTQ+-phobia and LGBTQ+ identity concealment, and then identify associations of derived classes with psychological distress. METHODS: We recruited and enrolled participants using nonprobability, cross-sectional online survey data collected between May and August 2020 (N = 482). We used a three-step latent class analysis (LCA) approach to identify unique classes of response patterns to LGBTQ+-related minority stressor subscale items (i.e., familial heterosexist experiences, LGBTQ+-related family rejection, internalized LGBTQ+-phobia and LGBTQ+ identity concealment), and multinomial logistic regression to characterize the associations between the derived classes and psychological distress. RESULTS: Five distinct latent classes emerged from the LCA: (1) low minority stress, (2) LGBTQ+ identity concealment, (3) family rejection, (4) moderate minority stress and (5) high minority stress. Participants who were classified in the high and moderate minority stress classes were more likely to suffer from moderate and severe psychological distress compared to those classified in the low minority stress class. Additionally, relative to those in the low minority stress class, participants who were classified in the LGBTQ+ identity concealment group were more likely to suffer from severe psychological distress. CONCLUSION: Familial heterosexist experiences, LGBTQ+-related family rejection, internalized LGBTQ+-phobia and LGBTQ+ identity concealment are four constructs that have been extensively examined as predictors for mental health outcomes among LGBTQ+ persons, and our study is among the first to reveal nuanced gradients of these stressors. Additionally, we found that more severe endorsement of minority stress was associated with greater psychological distress. Given our study results and the previously established negative mental health impacts of minority stressors among LGBTQ+ young adults, findings from our study can inform research, practice, and policy reform and development that could prevent and reduce mental health inequities among LGBTQ+ young adults.

Metabolomic profiles of ovariectomized mice and their associations with body composition and frailty-related parameters in postmenopausal women.

BACKGROUND: Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women's health. PURPOSE: To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women. METHODS AND RESULTS: Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk. CONCLUSIONS: Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women.

What Is A Family? A Constitutive-Affirmative Account.

Bio-heteronormative conceptions of the family have long reinforced a nuclear ideal of the family as a heterosexual marriage, with children who are the genetic progeny of that union. This ideal, however, has also long been resisted in light of recent social developments, exhibited through the increased incidence and acceptance of step-families, donor-conceived families, and so forth. Although to this end some might claim that the bio-heteronormative ideal is not necessary for a social unit to count as a family, a more systematic conceptualization of the family-the kind of family that matters morally-is relatively underexplored in the philosophical literature. This paper makes a start at developing and defending an account of the family that is normatively attractive and in line with the growing prevalence of non-conventional families and methods of family-formation. Our account, which we call a constitutive-affirmative model of the family, takes the family to be constituted by an ongoing process of relevant affective and affirmative relations between the putative family members.

Survival Analysis as a Basis for Testing Hypotheses when Using Quantitative Ordinal Scale Disease Severity Data.

Disease severity in plant pathology is often measured by the amount of a plant or plant part that exhibits disease symptoms. This is typically assessed using a numerical scale, which allows a standardized, convenient, and quick method of rating. These scales, known as quantitative ordinal scales (QOS), divide the percentage scale into a predetermined number of intervals. There are various ways to analyze these ordinal data, with traditional methods involving the use of midpoint conversion to represent the interval. However, this may not be precise enough, as it is only an estimate of the true value. In this case, the data may be considered interval-censored, meaning that we have some knowledge of the value but not an exact measurement. This type of uncertainty is known as censoring, and techniques that address censoring, such as survival analysis (SA), use all available information and account for this uncertainty. To investigate the pros and cons of using SA with QOS measurements, we conducted a simulation based on three pathosystems. The results showed that SA almost always outperformed midpoint conversion with data analyzed using a t test, particularly when data were not normally distributed. Midpoint conversion is currently a standard procedure. In certain cases, the midpoint approach required a 400% increase in sample size to achieve the same power as the SA method. However, as the mean severity increases, fewer additional samples are needed (approximately an additional 100%), regardless of the assessment method used. Based on these findings, we conclude that SA is a valuable method for enhancing the power of hypothesis testing when analyzing QOS severity data. Future research should investigate the wider use of survival analysis techniques in plant pathology and their potential applications in the discipline.

Search for Boosted Dark Matter in COSINE-100.

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.

An Understated Comorbidity: The Impact of Homelessness on Traumatic Brain Injury.

Traumatic brain injury (TBI), a neurovascular injury caused by external force, is a common diagnosis among veterans and those experiencing homelessness (HL). There is a significant overlap in the veteran and homeless population, possibly accounting for the two to seven times greater incidence of TBI among those experiencing HL than the general population. Despite these statistics, individuals experiencing HL are often underdiagnosed and ineffectively treated for TBI. We introduced a novel model of HL. Over 5 weeks, adult Sprague-Dawley rats were randomly assigned to one of the following conditions: TBI only, HL only, TBI + HL, or control (n = 9 per group). To emulate HL, animals (2 animals per cage) were exposed to soiled beddings for 5 weeks. Subsequently, animals were introduced to TBI by using the moderate controlled cortical impact model, then underwent 4 consecutive days of behavioral testing (beam walk (BW), elevated body swing test (EBST), forelimb akinesia (FA), paw grasp (PG), Rotorod, and elevated T-maze). Nissl staining was performed to determine the peri-impact cell survival and the integrity of corpus callosum area. Motor function was significantly impaired by TBI, regardless of housing (beam walk or BW 85.0%, forelimb akinesia or FA 104.7%, and paw grasp or PG 100% greater deficit compared to control). Deficits were worsened by HL in TBI rats (BW 93.3%, FA 40.5%, and PG 50% greater deficit). Two-way ANOVA revealed BW (F(4, 160) = 31.69, p < 0.0001), FA (F(4, 160) = 13.71, p < 0.0001), PG (F(4, 160) = 3.873, p = 0.005), Rotorod (F(4, 160), p = 1.116), and EBST (F(4, 160) = 6.929, p < 0.0001) showed significant differences between groups. The Rotorod and EBST tests showed TBI-induced functional deficits when analyzed by day, but these deficits were not exacerbated by HL. TBI only and TBI + HL rats exhibited typical cortical impact damage (F(3,95) = 51.75, p < 0.0001) and peri-impact cell loss compared to control group (F(3,238) = 47.34, p < 0.0001). Most notably, TBI + HL rats showed significant alterations in WM area measured via the corpus callosum (F(3, 95) = 3.764, p = 0.0133). Worsened behavioral outcomes displayed by TBI + HL rats compared to TBI alone suggest HL contributes to TBI functional deficits. While an intact white matter, such as the corpus callosum, may lessen the consequent functional deficits associated with TBI by enhancing hemispheric communications, there are likely alternative cellular and molecular pathways mitigating TBI-associated inflammatory or oxidative stress responses. Here, we showed that the environmental condition of the patient, i.e., HL, participates in white matter integrity and behavioral outcomes, suggesting its key role in the disease diagnosis to aptly treat TBI patients.

Who should provide the uterus? The ethics of live donor recruitment for uterus transplantation.

Uterus transplantation (UTx) is an experimental surgery likely to face the issue of organ shortage. In my article, I explore how this issue might be addressed by changing the prevailing practices around live uterus donor recruitment. Currently, women with children - often the mothers of recipients - tend to be overrepresented as donors. Yet, other potentially eligible groups who may have an interest in providing their uterus - such as transgender men, or cisgender women who do not wish to gestate or to have children - tend to be excluded as potential donors. Moving forward, I recommend that donor inclusion criteria for UTx be broadened to be more inclusive of these latter groups.

Safety and efficacy of trastuzumab biosimilar plus irinotecan or gemcitabine in patients with previously treated HER2 (ERBB2)-positive non-breast/non-gastric solid tumors: a phase II basket trial with circulating tumor DNA analysis.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) (ERBB2)-directed agents are standard treatments for patients with HER2-positive breast and gastric cancer. Herein, we report the results of an open-label, single-center, phase II basket trial to investigate the efficacy and safety of trastuzumab biosimilar (Samfenet®) plus treatment of physician's choice for patients with previously treated HER2-positive advanced solid tumors, along with biomarker analysis employing circulating tumor DNA (ctDNA) sequencing. METHODS: Patients with HER2-positive unresectable or metastatic non-breast, non-gastric solid tumors who failed at least one prior treatment were included in this study conducted at Asan Medical Center, Seoul, Korea. Patients received trastuzumab combined with irinotecan or gemcitabine at the treating physicians' discretion. The primary endpoint was the objective response rate as per RECIST version 1.1. Plasma samples were collected at baseline and at the time of disease progression for ctDNA analysis. RESULTS: Twenty-three patients were screened from 31 December 2019 to 17 September 2021, and 20 were enrolled in this study. Their median age was 64 years (30-84 years), and 13 patients (65.0%) were male. The most common primary tumor was hepatobiliary cancer (seven patients, 35.0%), followed by colorectal cancer (six patients, 30.0%). Among 18 patients with an available response evaluation, the objective response rate was 11.1% (95% confidence interval 3.1% to 32.8%). ERBB2 amplification was detected from ctDNA analysis of baseline plasma samples in 85% of patients (n = 17), and the ERBB2 copy number from ctDNA analysis showed a significant correlation with the results from tissue sequencing. Among 16 patients with post-progression ctDNA analysis, 7 (43.8%) developed new alterations. None of the patients discontinued the study due to adverse events. CONCLUSIONS: Trastuzumab plus irinotecan or gemcitabine was safe and feasible for patients with previously treated HER2-positive advanced solid tumors with modest efficacy outcomes, and ctDNA analysis was useful for detecting HER2 amplification.

Development and initial psychometric properties of the Warwick-Edinburgh Mental Wellbeing Scale-Intellectual Disability version.

BACKGROUND: The Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS; Tennant et al., 2007) is yet to be validated in the intellectual disability (ID) population. The aim of this study was to report the development process and assess the psychometric properties of a newly adapted version of the WEMWBS and the Short WEMWBS for individuals with mild to moderate IDs (WEMWBS-ID/SWEMWBS-ID). METHOD: The WEMWBS item wordings and response options were revised by clinicians and researchers expert in the field of ID, and a visual aid was added to the scale. The adapted version was reviewed by 10 individuals with IDs. The measure was administered by researchers online using screenshare, to individuals aged 16+ years with mild to moderate IDs. Data from three UK samples were collated to evaluate the WEMWBS-ID (n = 96). A subsample (n = 22) completed the measure again 1 to 2 weeks later to assess test-retest reliability, and 95 participants additionally completed an adapted version of the adapted Rosenberg Self-Esteem Scale to examine convergent validity. Additional data from a Canadian sample (n = 27) were used to evaluate the SWEMWBS-ID (n = 123). RESULTS: The WEMWBS-ID demonstrated good internal consistency (ω = 0.77-0.87), excellent test-retest reliability [intraclass correlation coefficient (ICC) = .88] and good convergent validity with the self-esteem scale (r = .48-.60) across samples. A confirmatory factor analysis for a single factor model demonstrated an adequate fit. The SWEMWBS-ID showed poor to good internal consistency (ω = 0.36-0.74), moderate test-retest reliability (ICC = .67) and good convergent validity (r = .48-.60) across samples, and a confirmatory factor analysis indicated good model fit for a single factor structure. CONCLUSIONS: The WEMWBS-ID and short version demonstrated promising psychometric properties, when administered virtually by a researcher. Further exploration of the scales with larger, representative samples is warranted.

Self-esteem and its relationship with depression and anxiety in adults with intellectual disabilities: a systematic literature review.

BACKGROUND: In the general population, low self-esteem has been linked with poorer mental and physical health. This systematic literature review aimed to summarise and evaluate the findings of studies that examined self-esteem in adults with intellectual disabilities and links with mental health outcomes. METHOD: A systematic search of PsycINFO, Web of Science and CINAHL was conducted to identify studies published between 1990 and 2021. The studies were appraised using the QualSyst tool. RESULTS: Twenty-six articles were identified of which two studies were removed from the review due to low quality. Studies reported mixed evidence regarding levels of self-esteem compared with the general population. Engagement in activities appeared to be linked with positive self-esteem, and perception of negative interpersonal life events as having a negative impact was associated with lower self-esteem. There was evidence of co-occurrence of low self-esteem and depression, but no studies examined the relationship between self-esteem and anxiety. CONCLUSION: Reviewed studies provided mixed evidence on levels of self-esteem in this population, suggesting that factors such as engagement in life were related to higher self-esteem and demonstrating the co-occurrence of low self-esteem and depression. However, clear causal links have yet to be identified, and more research is needed using longitudinal designs to answer questions about trajectory.

Psychometric properties of measures designed to assess common mental health problems and wellbeing in adults with intellectual disabilities: a systematic review.

BACKGROUND: Multiple measures of mental health problems and mental wellbeing for adults with intellectual disabilities are available, but investigations into their reliability and validity are still in the early stages. The aim of this systematic review was to provide an update to previous evaluations of measures of common mental health problems and wellbeing in adults with mild to moderate intellectual disabilities (ID). METHODS: A systematic search was performed across three databases (MEDLINE, PsycINFO and SCOPUS). The literature search was limited to the years from 2009 to 2021 and to the original English versions. Ten papers evaluating nine measures were reviewed, and the psychometric properties of these measures were discussed using the Characteristics of Assessment Instructions for Psychiatric Disorders in Persons with Intellectual Developmental Disorders as a framework. RESULTS: Four measures had at least one rating of 'good' across both dimensions of reliability and at least one dimension of validity and were deemed to have promising psychometric properties: the Clinical Outcomes in Routine Evaluation-Learning Disabilities, Impact of Events Scale-Intellectual Disabilities, Lancaster and Northgate Trauma Scales and Self-Assessment and Intervention (self-report section). Additionally, these measures were developed through consultations with mental health professionals and/or people with IDs and thus were deemed to have good content validity. CONCLUSIONS: This review informs measurement choice for researchers and clinicians while highlighting a need for continued research efforts into the quality of measures available for people with IDs. The results were limited by incomplete psychometric evaluations of measures available. A paucity of psychometrically robust measures of mental wellbeing was observed.

Surrogacy: beyond the commercial/altruistic distinction.

In this article, I critique the commonly accepted distinction between commercial and altruistic surrogacy arrangements. The moral legitimacy of surrogacy, I claim, does not hinge on whether it is paid ('commercial') or unpaid ('altruistic'); rather, it is best determined by appraisal of virtue-abiding conditions constitutive of the surrogacy arrangement. I begin my article by problematising the prevailing commercial/altruistic distinction; next, I demonstrate that an assessment of the virtue-abiding or non-virtue-abiding features of a surrogacy is crucial to navigating questions about the moral legitimacy of surrogacy; in the final part, I reject other moral heuristics that might be proposed as alternatives to the commercial/altruistic dichotomy, and reiterate that a virtue-ethical framework is the most suitable way forward.

Cluster Analysis of DSC MRI, Dynamic Contrast-Enhanced MRI, and DWI Parameters Associated with Prognosis in Patients with Glioblastoma after Removal of the Contrast-Enhancing Component: A Preliminary Study.

BACKGROUND AND PURPOSE: No report has been published on the use of DSC MR imaging, DCE MR imaging, and DWI parameters in combination to create a prognostic prediction model in glioblastoma patients. The aim of this study was to develop a machine learning-based model to find preoperative multiparametric MR imaging parameters associated with prognosis in patients with glioblastoma. Normalized CBV, volume transfer constant, and ADC of the nonenhancing T2 high-signal-intensity lesions were evaluated using K-means clustering. MATERIALS AND METHODS: A total of 142 patients with glioblastoma who underwent preoperative MR imaging and total resection were included in this retrospective study. From the normalized CBV, volume transfer constant, and ADC maps, the parametric data were sorted using the K-means clustering method. Patients were divided into training and test sets (ratio, 1:1), and the optimal number of clusters was determined using receiver operating characteristic analysis. Kaplan-Meier survival analysis and log-rank tests were performed to identify potential parametric predictors. A multivariate Cox proportional hazard model was conducted to adjust for clinical predictors. RESULTS: The nonenhancing T2 high-signal-intensity lesions were divided into 6 clusters. The cluster (class 4) with the relatively low normalized CBV and volume transfer constant value and the lowest ADC values was most associated with predicting glioblastoma prognosis. The optimal cutoff of the class 4 volume fraction of nonenhancing T2 high-signal-intensity lesions predicting 1-year progression-free survival was 9.70%, below which the cutoff was associated with longer progression-free survival. Two Kaplan-Meier curves based on the cutoff value showed a statistically significant difference (P = .037). When we adjusted for all clinical predictors, the cluster with the relatively low normalized CBV and volume transfer constant values and the lowest ADC value was an independent prognostic marker (hazard ratio, 3.04; P = .048). The multivariate Cox proportional hazard model showed a concordance index of 0.699 for progression-free survival. CONCLUSIONS: Our model showed that nonenhancing T2 high-signal-intensity lesions with the relatively low normalized CBV, low volume transfer constant values, and the lowest ADC values could serve as useful prognostic imaging markers for predicting survival outcomes in patients with glioblastoma.

Regional and annual patterns in respiratory virus co-infection etiologies and antibiotic prescriptions for pediatric mycoplasma pneumoniae pneumonia.

OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae) pneumonia is the second-most common cause of community-acquired pneumonia (CAP). This study aimed at investigating into the prevalence of macrolide-resistant M. pneumoniae (MRMP) with respiratory virus co-infection and the antibiotic prescriptions in children with CAP in four provinces in Korea, and to assess the variations in the findings across regions and throughout the year. PATIENTS AND METHODS: This prospective study was conducted in 29 hospitals in Korea between July 2018 and June 2020. Among the enrolled 1,063 children with CAP, all 451 patients with M. pneumoniae underwent PCR assays of M. pneumoniae and respiratory viruses, and the presence of point mutations of residues 2063 and 2064 was evaluated. RESULTS: Gwangju-Honam (88.6%) showed the highest prevalence of MRMP pneumonia, while Daejeon-Chungcheong (71.3%) showed the lowest, although the differences in prevalence were not significant (p=0.074). Co-infection of M. pneumoniae pneumonia and respiratory virus was observed in 206 patients (45.4%), and rhinovirus co-infection (101 children; 22.2%) was the most frequent. The prevalence of MRMP pneumonia with respiratory virus co-infection and the antibiotic prescriptions differed significantly among the four provinces (p < 0.05). The monthly rate of MRMP pneumonia cases among all cases of M. pneumoniae pneumonia and tetracycline or quinolone prescriptions did not differ significantly among the four regions (trend p > 0.05) during the study period. CONCLUSIONS: The prevalence of M. pneumoniae pneumonia with virus co-infection and antibiotic prescriptions could differ according to region, although the MRMP pneumonia rate showed no difference within Korea.

Development of Older Adult Food Insecurity Index to Assess Food Insecurity of Older Adults.

OBJECTIVES: Quantifying the number of older adults that are food insecure in a specific geographic area is critical in developing and scaling public health prevention and response programs at the local level. However, current estimates of older adult food insecurity only consider financial constraints, following the same methodology as the general population, even though the drivers for older adults are different and multidimensional. This study aims to build a general approach to quantify the food-insecurity among older adults at the local level, using publicly available data that can be easily obtained across the country. METHODS: 13 risk factors for food insecurity among older adults were identified leveraging existing studies, following the Social Ecological Model (SEM), and the weighted impact of each factor was determined. Publicly available data sources were identified for each factor, ZIP code level data was compared to national averages, and the weighted data for each factor were aggregated to determine the overall food insecurity at the local level. RESULTS: Based on the averaged odds ratios across all the studies, of the 13 risk factors, beyond financial constraints, having a disability was the most impactful factor and distance to the nearest grocery store was the least impactful. A ZIP code level model of Honolulu County was developed as an example to demonstrate the approach, showing that food insecurity among older adults in the county was 2.5 times that which was reported from the Current Population Survey (16.5% versus 6.5%). CONCLUSION: This evidence-based model considered factors that impact food insecurity among older adults across all the spheres of the SEM. The drivers of food insecurity among older adults are different than the drivers for the general population, resulting in a higher percentage of older adults being food insecure than currently reported.

The limitations of liberal reproductive autonomy.

The common liberal understanding of reproductive autonomy - characterized by free choice and a principle of non-interference - serves as a useful way to analyse the normative appeal of having certain choices open to people in the reproductive realm, especially for issues like abortion rights. However, this liberal reading of reproductive autonomy only offers us a limited ethical understanding of what is at stake in many kinds of reproductive choices, particularly when it comes to different uses of reproductive technologies and third-party reproduction. This is because the liberal framework does not fully capture who benefits from which reproductive options, the extent of the risks and harms involved in various reproductive interventions, and the reasons for why people are driven to make certain reproductive choices.