Reflecting on the Importance of Family Building and Fertility Preservation: Transgender People's Experiences with Starting Gender-Affirming Treatment as an Adolescent.

Purpose: We aimed to investigate how adults, who started gender-affirming hormone treatment during adolescence, reflect on their reproductive decisions. Methods: We recruited transgender and gender-diverse (TGD) people who visited our gender identity clinic and commenced medical treatment in adolescence at least 9 years ago. We collected data through an online survey. Results: The cohort consisted of 89 participants (66 TGD people assigned female at birth (AFAB) and 23 TGD people assigned male at birth (AMAB) with a mean age of 32.4 years (range 25.5-51.2) at the time of study, and 15.6 years (range 11.5-20.6) at the start of medical treatment. All participants initiated medical treatment before 2014, when laws requiring sterilization for legal gender recognition were still in place, and only 30% of participants reported to have received information about fertility preservation, which none of them pursued. In addition, 96% of participants underwent gonadectomy and thus became permanently infertile, which was troublesome for 27%. With today's knowledge, 44% of TGD people AFAB and 35% of TGD people born AMAB would pursue fertility preservation. The percentage of participants with a (future) desire for children increased from 34% at the start of medical treatment (at adolescent age) to 56% at the time of this study (at adult age), of whom 23% had currently started a family. Conclusion: It is important to inform transgender adolescents about the effect of medical treatment on fertility and the options for fertility preservation since many may develop a desire for (biological) children when they reach adulthood.

Simple Climate Models That Can Be Used in Primary, Secondary, and Tertiary Education.

Climate change is of great concern to all age groups but in particular to children. "Simple" climate models have been in place for a long time and can be used effectively with post-16 students. For younger children, modifications are required, and we describe in this paper the development and use of two such models. The first (the Granny Model) is a pictorial version of the model that has been used extensively with primary and early secondary school aged children (14 and younger). The second is an online version of the simple climate model that can be used without recourse to the underpinning mathematics and science but allows children to experiment with changing variables and how these changes affect the average surface temperature of the Earth.

Optimization path of primary public health service talent team construction: a largescale survey in Huaihai Economic Zone, China.

Background: The primary public health service system is indispensable for the implementation of the "Healthy China 2030" strategy, and primary healthcare workers, as the key drivers of this system, play a pivotal role in its development and establishment to ensure population well-being. In developing countries, such as China, primary public health systems are still weak, and in order to address this phenomenon, health system reform is needed, and primary public health personnel are crucial to health system reform. The current situation of primary public health workers in low-income and developing countries is characterized by varying degrees of problems that need improvement. Objectives: The purpose of this study is to understand the current situation of primary public health service workforce building, analyze the existing problems of the workforce, put forward suggestions for improvement and explore countermeasures, and provide Chinese wisdom and a reference basis for primary public health workforce building in the world, especially in developing countries. Methods: Combining the Work-Family Conflict Scale, Copenhagen Burnout Inventory, Minnesota Satisfaction Questionnaire, and Turnover Intention Scale, a relevant survey questionnaire was designed to quantitatively investigate the baseline characteristics of primary public health service institutions and their staff in four representative cities in the Huaihai Economic Zone: Xuzhou in Jiangsu Province, Linyi in Shandong Province, Shangqiu in Henan Province, and Huaibei in Anhui Province. The collected data were analyzed and processed using SPSS 25.0 statistical analysis software through univariate analysis and logistic regression analyses. Methods such as one-way ANOVA, Logistic regression analysis, and independent samples t-test were used to analyze the influencing factors of primary public health workforce development. Results: The current work intensity at the primary public health level is currently high, the salary and benefits cannot meet the needs of most primary public health personnel, and the competition between work and family in terms of time and resources is pronounced, and the majority of primary public health personnel are dissatisfied with the status quo of "doing more work for less reward" and the poor social security. Emotional exhaustion, depersonalization, and a sense of personal accomplishment were positively correlated with the tendency to leave (all p < 0.01), and the burnout and emotional exhaustion of primary public health workers were intense. Conclusion: Primary public health personnel play an important role in providing primary public health services. However, the current working conditions of junior public health personnel in the Huaihai Economic Zone are influenced by factors such as workload, income level, and employment situation improvement, leading to low job satisfaction, significant work-family conflicts, and high turnover intention. In this context, based on the opinions of grassroots administrative departments and internationally relevant experiences, a series of suggestions have been proposed to improve the professional service level, job satisfaction, and occupational identity of staff members. These suggestions make valuable contributions to both the Huaihai Economic Zone and countries worldwide in safeguarding individual health and promoting national primary healthcare reform.

Human Ovarian Surface Epithelium Organoids as a Platform to Study Tissue Regeneration.

The ovarian surface epithelium (OSE), the outermost layer of the ovary, undergoes rupture during each ovulation and plays a crucial role in ovarian wound healing while restoring ovarian integrity. Additionally, the OSE may serve as the source of epithelial ovarian cancers. Although the OSE regenerative properties have been well studied in mice, understanding the precise mechanism of tissue repair in the human ovary remains hampered by limited access to human ovaries and suitable in vitro culture protocols. Tissue-specific organoids, miniaturized in vitro models replicating both structural and functional aspects of the original organ, offer new opportunities for studying organ physiology, disease modeling, and drug testing. Here, we describe a method to isolate primary human OSE (hOSE) from whole ovaries and establish hOSE organoids. We include a morphological and cellular characterization showing heterogeneity between donors. Additionally, we demonstrate the capacity of this culture method to evaluate hormonal effects on OSE-organoid growth over a 2-week period. This method may enable the discovery of factors contributing to OSE regeneration and facilitate patient-specific drug screenings for malignant OSE.

Association of blood cadmium, lead, and mercury with anxiety: a cross-sectional study from NHANES 2007-2012.

Objectives: The purpose of this paper is to explore the relationship between blood levels of cadmium, lead, and mercury and anxiety in American adults. Methods: Blood metals and self-reported anxiety days were extracted from laboratory data and questionnaire data, respectively, using NHANES data from 2007-2012. Weighted logistic regression was used to assess the relationship between cadmium, lead and mercury with anxiety. Restricted cubic spline was used to visualize the non-linear relationship between metal concentrations and anxiety. Weighted quantile sum (WQS) regression was used to investigate the effect of combined exposure to the three metals on anxiety. Results: The prevalence of anxiety in adults was 26.0%. After adjusting for potential confounding variables, cadmium levels in the highest quartile (Q4) were associated with a higher risk of anxiety compared to the lowest quartile (Q1) (OR = 1.279, 95% CI: 1.113-1.471, p < 0.01). Restricted cubic spline analysis indicated a positive association between blood cadmium levels and anxiety. Furthermore, co-exposure to multiple heavy metals was positively associated with anxiety risk (WQS positive: OR = 1.068, 95% CI: 1.016-1.160, p < 0.05), with cadmium contributing the most to the overall mixture effect. Compared to the Light RPA, the Vigorous/Moderate RPA group had a relatively low risk of anxiety after cadmium exposure. Conclusion: High levels of blood cadmium are positively associated with the development of anxiety disorders, which needs to be further verified in future studies.

Major Complications of Deep Venous Stenting.

INTRODUCTION: Deep venous stent placement has developed into a primary treatment modality for venous obstruction in recent decades. Reported rates of complications are low in the literature and are based mainly on case reports and single-centre cohorts. Interventionalists performing these procedures must be aware of the occurrence of complications associated with stent placement to counsel patients adequately and promote avoidance through optimal procedural approach. This study aims to determine the incidence of serious complications associated with iliocaval and iliofemoral stent placement in a cohort of patients from 3 major tertiary deep venous referral centres. METHODS: Data were collated from January 2014 to September 2023. The following major complications were included in the analysis: death, major bleeding requiring transfusion, massive pulmonary embolism, any complication which required endovascular or open surgical intervention, vessel rupture, acute kidney injury requiring dialysis, stent crushing, fracture, migration, involution or erosion. RESULTS: One thousand eight hundred fourteen (1814) patients were treated for acute or chronic deep venous pathology during the 9-year study period. Sixty-one patients (3.3%) experienced a major stent-related complication. The most frequently reported complication was stent crushing (n = 18, 29.5%), followed by stent fracture (n = 10, 16.4%) and erosion of the stent through the vessel wall (n = 8, 13.1%). Death was a rare event (0.2%). CONCLUSION: Deep venous stent placement is a safe procedure with low rates of major complications. It is incumbent upon operators to be aware of the risks associated with these procedures, however, rare, so that they may obtain fully informed consent from patients.

Socioeconomic benefits associated with bats.

BACKGROUND: While bats are tremendously important to global ecosystems, they have been and continue to be threatened by loss of habitat, food, or roosts, pollution, bat diseases, hunting and killing. Some bat species have also been implicated in the transmission of infectious disease agents to humans. While One Health efforts have been ramped up recently to educate and protect human and bat health, such initiatives have been limited by lack of adequate data on the pathways to ensure their support. For instance, data on the role of bats in supporting different components of human welfare assets would be utilized as a stepping stone to champion conservation campaigns. Unfortunately, these data are limited and efforts to synthesize existing literature have majorly focused on few components human welfare leaving other important aspects. METHODS: Here, we analyze benefits associated with bats in the context of welfare economics considering all the asset components. We surveyed scientific and gray literature platforms utilizing particular keywords. We then classified these values using integrated approaches to understand different values across human welfare assets of "health," "material and immaterial assets," "security or safety" and "social or cultural or spiritual relations". RESULTS: We found 235 papers from different countries indicating that bats play fundamental roles in supporting human welfare. These benefits were more prevalent in Asia and Africa. In terms of the use of bats to support welfare assets, bats were majorly utilized to derive material and immaterial benefits (n = 115), e.g., food and income. This was followed by their use in addressing health challenges (n = 99), e.g., treatment of ailments. There was a similarity in the benefits across different regions and countries. CONCLUSION: These results indicate potential opportunities for strengthening bat conservation programs. We recommend more primary studies to enhance understanding of these benefits as well as their effectiveness in deriving the perceived outcomes.

Association of Ground Glass Opacities with Systemic Inflammation and Progression of Emphysema.

RATIONAL: Ground glass opacities (GGO) in the absence of interstitial lung disease are understudied. OBJECTIVE: To assess the association of GGO with white blood cells (WBCs) and progression of quantified chest CT emphysema. METHODS: We analyzed data of participants in the Subpopulations and Intermediate Outcome Measures In COPD Study (SPIROMICS). Chest radiologists and pulmonologists labeled regions of the lung as GGO and adaptive multiple feature method (AMFM) trained the computer to assign those labels to image voxels and quantify the volume of the lung with GGO (%GGOAMFM). We used multivariable linear regression, zero-inflated negative binomial, and proportional hazards regression models to assess the association of %GGOAMFM with WBC, changes in %emphysema, and clinical outcomes. MEASUREMENTS AND MAIN RESULTS: Among 2,714 participants, 1,680 had COPD and 1,034 had normal spirometry. Among COPD participants, based on the multivariable analysis, current smoking and chronic productive cough was associated with higher %GGOAMFM. Higher %GGOAMFM was cross-sectionally associated with higher WBCs and neutrophils levels. Higher %GGOAMFM per interquartile range at visit 1 (baseline) was associated with an increase in emphysema at one-year follow visit by 11.7% (Relative increase; 95%CI 7.5-16.1%;P<0.001). We found no association between %GGOAMFM and one-year FEV1 decline but %GGOAMFM was associated with exacerbations and all-cause mortality during a median follow-up time of 1,544 days (Interquartile Interval=1,118-2,059). Among normal spirometry participants, we found similar results except that %GGOAMFM was associated with progression to COPD at one-year follow-up. CONCLUSIONS: Our findings suggest that GGOAMFM is associated with increased systemic inflammation and emphysema progression.

Glenohumeral internal rotation deficit: insights into pathologic, clinical, diagnostic, and therapeutic characteristics.

Overhead athletes undergo significant biomechanical adaptations due to repetitive overhead movements, primarily affecting the glenohumeral joint. These adaptations can lead to glenohumeral internal rotation deficit (GIRD), which is characterized by posterior capsule stiffness that results in glenohumeral joint translation and a shift in the center of gravity. The severity of GIRD is dependent upon the presence of asymmetry between gained external and lost internal rotation, which is defined clinically as an asymmetry exceeding 20º; this reduces the total range of motion compared to the unaffected limb or baseline measurements. Diagnosis is challenging, as it can be mistaken for chronic scapular adaptations. To mitigate misdiagnosis, a high clinical suspicion is crucial in overhead athletes, especially those who began performing forceful overhead movements before closure of growth plates. Periodic physical examinations should establish baseline values for glenohumeral rotation and track changes in glenohumeral motion to aid in diagnosis. Symptoms of GIRD include shoulder pain, stiffness, and decreased force exertion. Magnetic resonance imaging is the preferred imaging method for evaluating GIRD and assessing concomitant soft tissue pathologies. Untreated GIRD can lead to rotator cuff strength imbalances. Treatment mainly involves conservative measures, such as physical therapy, to improve internal rotation and alleviate posterior tightness. Surgical interventions are considered when symptoms persist despite conservative treatment with physical therapy or in the presence of concomitant pathologies.

Vessel and Airway Characteristics in One-Year Computed Tomography-defined Rapid Emphysema Progression: SPIROMICS.

Rationale: Rates of emphysema progression vary in chronic obstructive pulmonary disease (COPD), and the relationships with vascular and airway pathophysiology remain unclear. Objectives: We sought to determine if indices of peripheral (segmental and beyond) pulmonary arterial dilation measured on computed tomography (CT) are associated with a 1-year index of emphysema (EI; percentage of voxels <-950 Hounsfield units) progression. Methods: Five hundred ninety-nine former and never-smokers (Global Initiative for Chronic Obstructive Lung Disease stages 0-3) were evaluated from the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort: rapid emphysema progressors (RPs; n = 188, 1-year ΔEI > 1%), nonprogressors (n = 301, 1-year ΔEI ± 0.5%), and never-smokers (n = 110). Segmental pulmonary arterial cross-sectional areas were standardized to associated airway luminal areas (segmental pulmonary artery-to-airway ratio [PAARseg]). Full-inspiratory CT scan-derived total (arteries and veins) pulmonary vascular volume (TPVV) was compared with small vessel volume (radius smaller than 0.75 mm). Ratios of airway to lung volume (an index of dysanapsis and COPD risk) were compared with ratios of TPVV to lung volume. Results: Compared with nonprogressors, RPs exhibited significantly larger PAARseg (0.73 ± 0.29 vs. 0.67 ± 0.23; P = 0.001), lower ratios of TPVV to lung volume (3.21 ± 0.42% vs. 3.48 ± 0.38%; P = 5.0 × 10-12), lower ratios of airway to lung volume (0.031 ± 0.003 vs. 0.034 ± 0.004; P = 6.1 × 10-13), and larger ratios of small vessel volume to TPVV (37.91 ± 4.26% vs. 35.53 ± 4.89%; P = 1.9 × 10-7). In adjusted analyses, an increment of 1 standard deviation in PAARseg was associated with a 98.4% higher rate of severe exacerbations (95% confidence interval, 29-206%; P = 0.002) and 79.3% higher odds of being in the RP group (95% confidence interval, 24-157%; P = 0.001). At 2-year follow-up, the CT-defined RP group demonstrated a significant decline in postbronchodilator percentage predicted forced expiratory volume in 1 second. Conclusions: Rapid one-year progression of emphysema was associated with indices indicative of higher peripheral pulmonary vascular resistance and a possible role played by pulmonary vascular-airway dysanapsis.

Association of serum vitamin D with anxiety in US adults: a cross-sectional study.

Objective: There have been proposals that vitamin D may be associated with a reduction in the incidence of anxiety disorders. However, the findings thus far have been inconsistent, warranting further investigation. The purpose of this paper is to explore the link between serum vitamin D and anxiety. Methods: Data are from the National Health and Nutrition Examination Survey (NHANES) in the United States from 2007 to 2012. Study included a total of 12,232 participants, and through the multivariate logistic regression to study the relationship between serum vitamin D and anxiety, smooth curve fitting is used to study the nonlinear relationship between serum vitamin D levels and anxiety. Results: Serum vitamin D levels demonstrated a negative correlation with anxiety (p < 0.001). Vitamin D exhibited a significant impact on anxiety (Q4:OR = 0.774, 95% CI: 0.663-0.903, p < 0.01), and this effect remained significant even after adjusting for confounding variables (Q4:OR = 0.781, 95% CI: 0.669-0.912, p < 0.01). Smoothed curve fitting revealed a negative association between serum vitamin D levels and the risk of anxiety, and these findings persisted after accounting for confounding variables. Conclusion: Serum vitamin D levels were inversely associated with anxiety risk in US adults. In the future, more accurate prospective studies are needed to confirm this result.

LungViT: Ensembling Cascade of Texture Sensitive Hierarchical Vision Transformers for Cross-Volume Chest CT Image-to-Image Translation.

Chest computed tomography (CT) at inspiration is often complemented by an expiratory CT to identify peripheral airways disease. Additionally, co-registered inspiratory-expiratory volumes can be used to derive various markers of lung function. Expiratory CT scans, however, may not be acquired due to dose or scan time considerations or may be inadequate due to motion or insufficient exhale; leading to a missed opportunity to evaluate underlying small airways disease. Here, we propose LungViT- a generative adversarial learning approach using hierarchical vision transformers for translating inspiratory CT intensities to corresponding expiratory CT intensities. LungViT addresses several limitations of the traditional generative models including slicewise discontinuities, limited size of generated volumes, and their inability to model texture transfer at volumetric level. We propose a shifted-window hierarchical vision transformer architecture with squeeze-and-excitation decoder blocks for modeling dependencies between features. We also propose a multiview texture similarity distance metric for texture and style transfer in 3D. To incorporate global information into the training process and refine the output of our model, we use ensemble cascading. LungViT is able to generate large 3D volumes of size 320×320×320 . We train and validate our model using a diverse cohort of 1500 subjects with varying disease severity. To assess model generalizability beyond the development set biases, we evaluate our model on an out-of-distribution external validation set of 200 subjects. Clinical validation on internal and external testing sets shows that synthetic volumes could be reliably adopted for deriving clinical endpoints of chronic obstructive pulmonary disease.

One-third of amenorrheic transmasculine people on testosterone ovulate.

Transmasculine people usually reach amenorrhea within 6 months of adequate testosterone treatment. It is often assumed that no ovulation occurs during amenorrhea. However, in this study, we report recent ovulatory activity in amenorrheic transmasculine people on testosterone therapy at gender-affirming oophorectomy. Histological signs of recent ovulatory activity, including the presence of ovulatory follicles, corpus luteum, and corpus albicans, are observed in 17 of 52 individuals (33%). This is not significantly correlated to the duration, testosterone serum levels, or type of testosterone used. These results suggest that amenorrhea does not equal anovulation in transmasculine people on adequate testosterone therapy, emphasizing the importance of contraception for people who engage in sexual activity that can result in pregnancy.

Classification of Atretic Small Antral Follicles in the Human Ovary.

The reproductive lifespan in humans is regulated by a delicate cyclical balance between follicular recruitment and atresia in the ovary. The majority of the small antral follicles present in the ovary are progressively lost through atresia without reaching dominance, but this process remains largely underexplored. In our study, we investigated the characteristics of atretic small antral follicles and proposed a classification system based on molecular changes observed in granulosa cells, theca cells, and extracellular matrix deposition. Our findings revealed that atresia spreads in the follicle with wave-like dynamics, initiating away from the cumulus granulosa cells. We also observed an enrichment of CD68+ macrophages in the antrum during the progression of follicular atresia. This work not only provides criteria for classifying three stages of follicular atresia in small antral follicles in the human ovary but also serves as a foundation for understanding follicular degeneration and ultimately preventing or treating premature ovarian failure. Understanding follicular remodeling in the ovary could provide a means to increase the number of usable follicles and delay the depletion of the follicular reserve, increasing the reproductive lifespan.

Flipping the Thinking on Equality, Diversity, and Inclusion. Why EDI Is Essential for the Development and Progression of the Chemical Sciences: A Case Study Approach.

All learners have a contribution to make to the development of the Chemical Sciences, be that in novel ways to teach, and their perspectives and contexts, but also in research, both in chemical education and the wider Chemical Sciences. Through four case studies, this paper explores interactions with diverse groups and how this has altered perspectives on both teaching and research. The case studies include work with visually impaired adults, a project bringing together First Peoples in Australia with academics to explore old ways (traditional science) and new ways (modern approaches), primary (elementary) school perspectives on teaching science, and a project in South Africa to connect university and township communities. Not only do these case studies demonstrate the immense value these diverse groups bring to our understanding about how to learn, but they also bring new perspectives on how to view and solve chemical problems.

Structural and functional analyses of viral H2 protein of the vaccinia virus entry fusion complex.

IMPORTANCE: Vaccinia virus infection requires virus-cell membrane fusion to complete entry during endocytosis; however, it contains a large viral fusion protein complex of 11 viral proteins that share no structure or sequence homology to all the known viral fusion proteins, including type I, II, and III fusion proteins. It is thus very challenging to investigate how the vaccinia fusion complex works to trigger membrane fusion with host cells. In this study, we crystallized the ectodomain of vaccinia H2 protein, one component of the viral fusion complex. Furthermore, we performed a series of mutational, biochemical, and molecular analyses and identified two surface loops containing 170LGYSG174 and 125RRGTGDAW132 as the A28-binding region. We also showed that residues in the N-terminal helical region (amino acids 51-90) are also important for H2 function.

Response to high dose ipilimumab plus temozolomide after progression on standard or low dose ipilimumab in advanced melanoma: a retrospective analysis.

Background: Despite advancements in checkpoint inhibitor-based immunotherapy, patients with advanced melanoma who have progressed on standard dose ipilimumab (Ipi) + nivolumab continue to have poor prognosis. Several studies support a dose-response activity of Ipi, and one promising combination is Ipi 10mg/kg (Ipi10) + temozolomide (TMZ). Methods: We performed a retrospective cohort analysis of patients with advanced melanoma treated with Ipi10+TMZ in the immunotherapy refractory/resistant setting (n = 6), using similar patients treated with Ipi3+TMZ (n = 6) as comparison. Molecular profiling by whole exome sequencing (WES) and RNA-seq of tumors harvested through one responder's treatment was performed. Results: With a median follow up of 119 days, patients treated with Ipi10+TMZ had statistically significant longer median progression free survival of 144.5 days (range 27-219) vs 44 (26-75) in Ipi3+TMZ, p=0.04, and a trend for longer median overall survival of 154.5 days (27-537) vs 89.5 (26-548). All patients in the Ipi10 cohort had progressed on prior Ipi+Nivo. WES revealed only 12 shared somatic mutations including BRAF V600E. RNA-seq showed enrichment of inflammatory signatures, including interferon responses in metastatic lesions after standard dose Ipi + nivo and Ipi10 + TMZ compared to the primary tumor, and downregulated negative immune regulators including Wnt and TGFb signaling. Conclusion: Ipi10+TMZ demonstrated efficacy including dramatic responses in patients with advanced melanoma refractory to prior Ipi + anti-PD1, even with CNS metastases. Molecular data suggest a potential threshold of Ipi dose for activation of sufficient anti-tumor immune response, and higher dose Ipi is required for some patients.

Localization supervision of chest x-ray classifiers using label-specific eye-tracking annotation.

Convolutional neural networks (CNNs) have been successfully applied to chest x-ray (CXR) images. Moreover, annotated bounding boxes have been shown to improve the interpretability of a CNN in terms of localizing abnormalities. However, only a few relatively small CXR datasets containing bounding boxes are available, and collecting them is very costly. Opportunely, eye-tracking (ET) data can be collected during the clinical workflow of a radiologist. We use ET data recorded from radiologists while dictating CXR reports to train CNNs. We extract snippets from the ET data by associating them with the dictation of keywords and use them to supervise the localization of specific abnormalities. We show that this method can improve a model's interpretability without impacting its image-level classification.