Combinatorial transcription factor profiles predict mature and functional human islet α and β cells.

Islet-enriched transcription factors (TFs) exert broad control over cellular processes in pancreatic α and β cells, and changes in their expression are associated with developmental state and diabetes. However, the implications of heterogeneity in TF expression across islet cell populations are not well understood. To define this TF heterogeneity and its consequences for cellular function, we profiled more than 40,000 cells from normal human islets by single-cell RNA-Seq and stratified α and β cells based on combinatorial TF expression.

Debates in Pancreatic Beta Cell Biology: Proliferation Versus Progenitor Differentiation and Transdifferentiation in Restoring β Cell Mass.

In all forms of diabetes, β cell mass or function is reduced and therefore the capacity of the pancreatic cells for regeneration or replenishment is a critical need. Diverse lines of research have shown the capacity of endocrine as well as acinar, ductal and centroacinar cells to generate new β cells. Several experimental approaches using injury models, pharmacological or genetic interventions, isolation and expansion of putative progenitors followed by transplantations or a combination thereof have suggested several pathways for β cell neogenesis or regeneration.

What is a β cell? - Chapter I in the Human Islet Research Network (HIRN) review series.

Background: The pancreatic β cell, as the sole source of the vital hormone insulin, has been under intensive study for more than a century. Given the potential of newly created insulin-producing cells as a treatment or even cure of type 1 diabetes (T1D) and possibly in severe cases of type 2 diabetes (T2D), multiple academic and commercial laboratories are working to derive surrogate glucose-responsive, insulin-producing cells.

Scope Of Review: The recent development of advanced phenotyping technologies, including molecular, epigenomic, histological, or functional, have greatly improved our understanding of the critical properties of human β cells.

Computational Mechanism for the Effect of Psychosis Community Treatment: A Conceptual Review From Neurobiology to Social Interaction.

The computational underpinnings of positive psychotic symptoms have recently received significant attention. Candidate mechanisms include some combination of maladaptive priors and reduced updating of these priors during perception. A potential benefit of models with such mechanisms is their ability to link multiple levels of explanation, from the neurobiological to the social, allowing us to provide an information processing-based account of how specific alterations in self-self and self-environment interactions result in the experience of positive symptoms.

Emotion dysregulation and dissociation contribute to decreased heart rate variability to an acute psychosocial stressor in trauma-exposed Black women.

Reduced heart rate variability (HRV) in response to stress is a biomarker of emotion dysregulation (ED) and is related to posttraumatic stress disorder (PTSD), yet less is known about its role with dissociation in trauma-exposed adults. The goals of the current study were to examine unique patterns of associations between ED, dissociation, and PTSD with HRV at 15, 30, and 45 min (T1, T2, T3) following an acute psychosocial stressor task in a sample of 49 trauma-exposed, urban-dwelling Black women. Associations with baseline psychophysiology measures were also examined.

Computerized Assessment of Psychosis Risk.

Early detection and intervention with young people at clinical high risk (CHR) for psychosis is critical for prevention efforts focused on altering the trajectory of psychosis. Early CHR research largely focused on validating clinical interviews for detecting at-risk individuals; however, this approach has limitations related to: (1) specificity (i.e.

Experimental respiratory exposure to putative Gulf War toxins promotes persistent alveolar macrophage recruitment and pulmonary inflammation.

Aims: Respiratory disorders are a prominent component of Gulf War Illness. Although much of the underlying mechanisms of Gulf War Illness remain undefined, chronic immune dysfunction is a consistent feature of this multi-symptomatic, multi-organ disorder. Alveolar macrophages represent the predominant mononuclear phagocytes of the pulmonary mucosa, orchestrating the host response to pathogens and environmental stimuli.

Sex-Specific Associations Between Trauma Exposure, Pubertal Timing, and Anxiety in Black Children.

Recent research has linked early life stress (ELS), such as trauma exposure, with early puberty. Early puberty has also been identified as a risk factor for poor mental health outcomes. However, these two paths have primarily been examined independently.

Understanding Civilian Mental Health Providers' Knowledge in Providing Care for Active Duty Service Members: Opportunities for Improvement.

Introduction: There are a growing number of civilian mental health providers who are treating active duty service members (ADSM) from referrals of local emergency rooms, directly from military installations, or when a military mental health program is unavailable. Civilian providers may be unprepared to address issues that are unique to this population.

Aim: The purpose of this quality improvement project was to develop and implement a survey-based knowledge assessment, in order to assess civilian psychiatric advanced practice nurse's (APN) perceptions, knowledge, and practice of treating ADSMs.

Phase 1 Combination Study of the CHK1 Inhibitor Prexasertib and the PARP Inhibitor Olaparib in High-grade Serous Ovarian Cancer and Other Solid Tumors.

Purpose: Checkpoint kinase 1 (CHK1) plays a central role in the response to replication stress through modulation of cell-cycle checkpoints and homologous recombination (HR) repair. In BRCA-deficient cancers with or acquired PARP inhibitor resistance, the addition of the CHK1 inhibitor prexasertib to the PARP inhibitor olaparib compromises replication fork stability, as well as HR proficiency, allowing for sensitization to PARP inhibition.

Patients And Methods: This study followed a 3+3 design with a 7-day lead-in of olaparib alone, followed by 28-day cycles with prexasertib administered on days 1 and 15 in combination with an attenuated dose of olaparib on days 1-5 and 15-19.

Analysis of longitudinal head impact exposure and white matter integrity in returning youth football players.

Objective: The objective of this study was to characterize changes in head impact exposure (HIE) across multiple football seasons and to determine whether changes in HIE correlate with changes in imaging metrics in youth football players.

Methods: On-field head impact data and pre- and postseason imaging data, including those produced by diffusion tensor imaging (DTI), were collected from youth football athletes with at least two consecutive seasons of data. ANCOVA was used to evaluate HIE variations (number of impacts, peak linear and rotational accelerations, and risk-weighted cumulative exposure) by season number.

Impulsivity Mediates the Link between Childhood Sexual Abuse and Juvenile Incarceration among Low-Income African American Women.

A history of childhood trauma has been found to have a robust influence on juvenile delinquency, and evidence suggests that childhood sexual abuse is particularly common among female youth involved in the juvenile justice system. The current study sought to investigate impulsivity as a potential mediator of the relationship between childhood sexual abuse (CSA) and juvenile incarceration amongst a community sample of low-income, urban, African American adult women. Although impulsivity has been studied among justice-involved youth, few studies have examined the influence of impulsivity within the relationship between CSA and juvenile incarceration and no known studies have explored their relationship in community populations of African American women with histories of juvenile incarceration.

The roles of attachment and emotion dysregulation in the association between childhood maltreatment and PTSD in an inner-city sample.

Background: Most people will experience a traumatic event in their lifetime, but only a subset (<10%) will develop posttraumatic stress disorder (PTSD).

Objective: To facilitate prevention and intervention of PTSD, it is important to understand how risk and resilience factors interact with one another to explain individual differences in risk for PTSD, especially in underprivileged groups, who often experience greater burden of trauma and PTSD.

Method: The current study utilized multiple and moderated regression to examine the relation between childhood maltreatment and adulthood PTSD risk in the context of various attachment patterns and emotion dysregulation in a sample (n = 856) of mostly low-income, African American participants.

Surgical removal of a migrating intraspinal bullet: illustrative case.

Background: Management of gunshot wounds to the spine with subsequent spinal cord injury is a controversial topic among spine surgeons. Possible complications of retained intradural bullets include delayed neurological deficits, spinal instability, and lead toxicity. The authors' purpose is to review the potential complications of retained intraspinal bullets and the surgical indications for intraspinal bullet removal.

Regional White Matter Diffusion Changes Associated with the Cumulative Tensile Strain and Strain Rate in Nonconcussed Youth Football Players.

The purpose of this study is to assess the relationship between regional white matter diffusion imaging changes and finite element strain measures in nonconcussed youth football players. Pre- and post-season diffusion-weighted imaging was performed in 102 youth football subject-seasons, in which no concussions were diagnosed. The diffusion data were normalized to the IXI template.

Increased face detection responses on the mooney faces test in people at clinical high risk for psychosis.

Identifying state-sensitive measures of perceptual and cognitive processes implicated in psychosis may allow for objective, earlier, and better monitoring of changes in mental status that are predictive of an impending psychotic episode, relative to traditional self-report-based clinical measures. To determine whether a measure of visual perception that has demonstrated sensitivity to the clinical state of schizophrenia in multiple prior studies is sensitive to features of the at-risk mental state, we examined differences between young people identified as being at clinical high risk for psychosis (CHR; n = 37) and non-psychiatric matched controls (n = 29) on the Mooney Faces Test (MFT). On each trial of the MFT, participants report whether they perceive a face in a degraded face image.

Trauma exposure and stress-related disorders in a large, urban, predominantly African-American, female sample.

The current study investigated the relationship between trauma exposure and psychopathology in a sample of predominately African-American women of low socioeconomic status (SES). Women (N = 7430) were recruited from medical clinics at two large public hospitals in Atlanta, GA, from 2005 to 2017. Women were assessed for sociodemographics, life-course trauma burden, posttraumatic stress disorder (PTSD), and major depressive disorder (MDD) utilizing self-report and structured clinical interview assessments.

Spatiotemporal Heterogeneity of Zika Virus Transmission in Indonesia: Serosurveillance Data from a Pediatric Population.

The presence of Zika virus (ZIKV) in Indonesia has been recognized since the 1970s, but its transmission dynamics there have been poorly understood. To understand more fully the geographic distribution and burden of ZIKV infection, we performed retrospective serological tests on specimens collected from asymptomatic children age 5 to 9 years old living at 30 sites in 14 provinces. Of 870 serum samples tested, 9.

Effect of lisocabtagene maraleucel on HRQoL and symptom severity in relapsed/refractory large B-cell lymphoma.

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has shown efficacy as a third-line or later treatment in patients with relapsed/refractory large B-cell lymphoma (LBCL). Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire, we evaluated the impact of CAR T-cell treatment with lisocabtagene maraleucel (liso-cel) on health-related quality of life (HRQoL) and symptoms in patients with relapsed/refractory LBCL in the ongoing, open-label, nonrandomized TRANSCEND NHL 001 trial. Clinically meaningful improvement was observed in EORTC QLQ-C30 scores for global health status/QoL, based on a minimally important difference of 10 points at 2 to 18 months after liso-cel infusion.

Endocrine toxicities of immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target two key signalling pathways related to T cell activation and exhaustion, by binding to and inhibiting cytotoxic T lymphocyte antigen 4 (CTLA4) or PD1 and its ligand PDL1. ICIs, such as nivolumab, pembrolizumab and ipilimumab, are approved for the treatment of numerous and diverse cancer types, in various combination regimens, and are now an established cornerstone of cancer therapeutics. Toxicities induced by ICIs are autoimmune in nature and are referred to as immune-related adverse events (irAEs); these events can affect any organ system in an unpredictable fashion.