Gene-Environment Interaction: Small Deletions (DELs) and Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) and Potential Implications for Therapy.

Arsenic (As) is a risk factor for non-melanoma skin cancer (NMSC). From a six-year follow-up study on 7000 adults exposed to As, we reported the associations of single-nucleotide variation in tumor tissue and gene expression. Here, we identify the associations of small deletions (DELs) and transcriptomic profiles in NMSC.

Association of Mutation and Gene Pathways in Colorectal Carcinoma: A Transcriptome- and Methylome-Wide Study and Potential Implications for Therapy.

Kirsten Rat Sarcoma () is the most commonly mutated oncogene in colorectal carcinoma (CRC). We have previously reported the interactions between microsatellite instability (MSI), DNA promoter methylation, and gene expression. In this study, we looked for associations between mutation, gene expression, and methylation that may help with precision medicine.

Predictive modeling for cell culture in commercial manufacturing of biotherapeutics.

The biopharmaceutical industry continually seeks advancements in the commercial manufacturing of therapeutic proteins, where mammalian cell culture plays a pivotal role. The current work presents a novel data-driven predictive modeling application designed to enhance the efficiency and predictability of cell culture processes in biotherapeutic production. The capability of the cloud-based digital data science application, developed using open-source tools, is demonstrated with respect to predicting bioreactor potency from at-line process parameters over a 5-day horizon.

Using a Novel, Subconjunctival, Sustained-Release Mitomycin C Formulation in a Rabbit Model of Filtration Surgery with Gel Stent Implantation.

To investigate gel stent implantation with and without intraoperative sustained-release mitomycin C (MMC SR) in a rabbit model for gel stent implantation, and to examine aqueous humor outflow (AHO) postimplantation. Four groups of rabbits were included. Group 1 was untreated (control).

Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma.

Purpose: Targeting solid tumors with chimeric antigen receptor (CAR) T cells remains challenging due to heterogenous target antigen expression, antigen escape, and the immunosuppressive tumor microenvironment (TME). Pancreatic cancer is characterized by a thick stroma generated by cancer-associated fibroblasts (CAF), which may contribute to the limited efficacy of mesothelin-directed CAR T cells in early-phase clinical trials. To provide a more favorable TME for CAR T cells to target pancreatic ductal adenocarcinoma (PDAC), we generated T cells with an antimesothelin CAR and a secreted T-cell-engaging molecule (TEAM) that targets CAF through fibroblast activation protein (FAP) and engages T cells through CD3 (termed mesoFAP CAR-TEAM cells).

Chemical genetic control of cytokine signaling in CAR-T cells using lenalidomide-controlled membrane-bound degradable IL-7.

CAR-T cell therapy has emerged as a breakthrough therapy for the treatment of relapsed and refractory hematologic malignancies. However, insufficient CAR-T cell expansion and persistence is a leading cause of treatment failure. Exogenous or transgenic cytokines have great potential to enhance CAR-T cell potency but pose the risk of exacerbating toxicities.

Anti-TACI single and dual-targeting CAR T cells overcome BCMA antigen loss in multiple myeloma.

Chimeric Antigen Receptor (CAR) T cells directed to B cell maturation antigen (BCMA) mediate profound responses in patients with multiple myeloma, but most patients do not achieve long-term complete remissions. In addition, recent evidence suggests that high-affinity binding to BCMA can result in on-target, off-tumor activity in the basal ganglia and can lead to fatal Parkinsonian-like disease. Here we develop CAR T cells against multiple myeloma using a binder to targeting transmembrane activator and CAML interactor (TACI) in mono and dual-specific formats with anti-BCMA.

The Importance of Non-Probability Samples in Minority Health Research: Lessons Learned from Studies of Transgender and Gender Diverse Mental Health.

Non-probability sampling methods utilize nonrandom research participant selection, which may generate study samples that are not representative of the general population. Non-probability sample studies are often regarded as inferior due to uncertainty about their generalizability and external validity. In reality, non-probability sampling offers advantages that make this method particularly valuable for minority health research.

Gender-Affirming Mental Health Care Access and Utilization Among Rural Transgender and Gender Diverse Adults in Five Northeastern U.S. States.

Purpose: Transgender and gender diverse (TGD) populations are burdened by substantial mental health disparities. The mental health needs of TGD people in rural areas remain largely unknown. This study sought to characterize gender-affirming mental health service access and utilization in a sample of TGD adults from predominantly rural areas in the northeastern United States.

Crustacean leg regeneration restores complex microanatomy and cell diversity.

Animals can regenerate complex organs, yet this process frequently results in imprecise replicas of the original structure. In the crustacean , embryonic and regenerating legs differ in gene expression dynamics but produce apparently similar mature structures. We examine the fidelity of leg regeneration using complementary approaches to investigate microanatomy, sensory function, cellular composition, and cell molecular profiles.

Gender-Affirming Primary Care Access Among Rural Transgender and Gender Diverse Adults in Five Northeastern U.S. States.

Little is known about the prevalence and predictors of gender-affirming primary care (GAPC) access among rural transgender and gender diverse (TGD) adults. This study therefore sought to characterize the prevalence and predictors of GAPC within a sample of rural TGD adults. A nonprobability convenience sample ( = 244) of rural TGD adults was recruited across five Northeastern U.

Distinct gene expression dynamics in developing and regenerating crustacean limbs.

Regenerating animals have the ability to reproduce body parts that were originally made in the embryo and subsequently lost due to injury. Understanding whether regeneration mirrors development is an open question in most regenerative species. Here, we take a transcriptomics approach to examine whether leg regeneration shows similar temporal patterns of gene expression as leg development in the embryo, in the crustacean .

A Pilot Sexual and Gender Minority Health Curriculum for the Largest Public Health Care System in the United States.

Problem: Sexual and gender minority (SGM) people face multiple health disparities. Clinicians often lack adequate training to address health needs of SGM people. In this setting, some health care organizations have sought to develop system-wide curricula to build clinician knowledge and capacity around SGM health.

Reported Pain in Cisgender Female and Transmasculine Patients Seeking Benign Breast Surgery.

Unlabelled: Benign breast surgery aims to treat the physical and psychological discomfort that may be associated with excess breast tissue. In this investigation, we present the first systematic examination and comparison of the determinants of pain and related symptomology in cisgender women and transmasculine individuals presenting for benign breast surgery.

Methods: To complete this study, we abstracted the intake forms of 128 transmasculine and 62 cisgender female patients who presented for benign breast surgery between August 2016 and July 2020.

Sexual Orientation and Gender Identity Data Collection at US Health Centers: Impact of City-Level Structural Stigma in 2018.

To examine the relationship between city-level structural stigma pertaining to sexual orientation and gender identity (SOGI) and completeness of patient SOGI data collection at US federally qualified health centers (FQHCs). We used the Human Rights Campaign's Municipal Equality Index to quantify city-level structural stigma against sexual and gender minority people in 506 US cities across 49 states. We ascertained the completeness of SOGI data collection at FQHCs from the 2018 Uniform Data System, which describes FQHC patient demographics and service utilization.

Understanding community member and health care professional perspectives on gender-affirming care-A qualitative study.

Background: Transgender and gender diverse (TGD) people experience significant barriers to accessing affirming health services. There is a paucity of literature examining how both community members and health care professionals (HCPs) understand potential causes and solutions for these barriers, particularly in non-urban settings.

Objective: We present the first systematic examination of perspectives from community members and HCPs regarding barriers to and solutions for promoting access to gender-affirming health care.

Association Between Gender-Affirming Hair Removal and Mental Health Outcomes.

This secondary analysis uses data from the 2015 US Transgender Survey to assess the association between gender-affirming hair removal procedures and mental health among transgender individuals.

A nonhuman primate model of blue light-induced progressive outer retina degeneration showing brimonidine drug delivery system-mediated cyto- and neuroprotection.

Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) characterized by atrophy of the retinal pigment epithelium (RPE), loss of photoreceptors, and disruption of choriocapillaris. Excessive light exposure is toxic to the retina and is a known risk factor for AMD. We first investigated the effects of blue light-induced phototoxicity on RPE and photoreceptors in nonhuman primates (NHPs, a model of progressive retinal degeneration) and then evaluated the potential cyto- and neuroprotective effects of the brimonidine drug delivery system (Brimo DDS).

Arthroscopic Matrix-Assisted Autologous Chondrocyte Transplantation Versus Microfracture: A 6-Year Follow-up of a Prospective Randomized Trial.

Background: Few randomized controlled trials with a midterm follow-up have compared matrix-assisted autologous chondrocyte transplantation (MACT) with microfracture (MFx) for knee cartilage lesions.

Purpose: To compare the structural, clinical, and safety outcomes at midterm follow-up of MACT versus MFx for treating symptomatic knee cartilage lesions.

Study Design: Randomized controlled trial; Level of evidence, 1.

Factors Leading to "Detransition" Among Transgender and Gender Diverse People in the United States: A Mixed-Methods Analysis.

There is a paucity of data regarding transgender and gender diverse (TGD) people who "detransition," or go back to living as their sex assigned at birth. This study examined reasons for past detransition among TGD people in the United States. A secondary analysis was performed on data from the U.

Associations Between Transgender Exclusion Prohibitions and Insurance Coverage of Gender-Affirming Surgery.

This investigation examined how coverage of gender-affirming surgery differs between states that do and do not have prohibitions against explicit transgender exclusions in private insurance. Insurance policies for gender-affirming surgery were obtained from the three largest insurers, by market share, in each state. Policies were reviewed manually between May and August of 2019.

Stroke, Epilepsy, and Antiepileptic Drugs as the Etiology of Major Depressive Disorder: A Case Report and Review.

Lateralized periodic discharges (LPDs) are a rare type of epileptiform activity. The authors of this brief report describe the association of LPDs with acute catastrophic depression in a previously healthy patient who had a series of neurobiological insults caused by a stroke and its treatment that led to the development of significant psychopathology. Through this case of new and debilitating depression that followed a recent stroke, subsequent development of LPDs, and treatment with levetiracetam, the authors highlight the complex interplay of structural, electrophysiologic, and pharmacologic factors in the pathogenesis of poststroke depression and the crucial role of having a broad biopsychosocial assessment for optimal diagnosis and management.