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Coffin–Siris syndrome (CSS) is a clinically and genetically heterogeneous developmental disorder, linked to disruption of the BAF chromatin‐remodeling complex. Recently, de novo missense and truncating variants have been reported in DPF2 in patients sharing some of the common features of CSS. Here we report a further individual harboring a novel de novo missense DPF2 variant, c.1066T>G, p.Cys356Gly. Structural modeling indicated that the predicted amino acid substitution affects a core residue required for zinc ion coordination and would likely alter the PHD2 domain structure of DPF2. The clinical presentation of Pierre Robin sequence and diaphragmatic hernia did not immediately suggest CSS, with the more common CSS features of hypoplastic toenails and characteristic facial features very subtle. This individual further broadens the phenotypic features of DPF2‐related CSS, as well as CSS more generally. [ABSTRACT FROM AUTHOR]

Poor response to Bacillus Calmette-Guérin (BCG) immunotherapy remains a major barrier in the management of patients with non-muscle invasive bladder cancer (NMIBC). Multiple factors are associated with poor outcomes, including biological aging and female sex. More recently, it has emerged that a B-cell infiltrated pre-treatment immune microenvironment of NMIBC tumors can influence the response to intra-vesically administered BCG. The mechanisms underlying the roles of B cells in NMIBC are poorly understood. Here, we show that B-cell dominant tertiary lymphoid structures (TLSs), a hallmark feature of the chronic mucosal immune response, are abundant and located close to the epithelial compartment in pre-treatment tumors from BCG non-responders. Digital spatial proteomic profiling of whole tumor sections from male and female patients with NMIBC who underwent treatment with intravesical BCG, revealed higher expression of immune exhaustion-associated proteins within the tumor-adjacent TLSs in both responders and non-responders. Chronic local inflammation, induced by the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) carcinogen, led to TLS formation with recruitment and differentiation of the immunosuppressive atypical B-cell (ABC) subset within the bladder microenvironment, predominantly in aging female mice compared to their male counterparts. Depletion of ABCs simultaneous to BCG treatment delayed cancer progression in female mice. Our findings provide evidence indicating a role for ABCs in BCG response and will inform future development of therapies targeting the B cell-exhaustion axis.

Adrenal cavernous hemangiomas are a rare, benign, and non-functional tumor. We report a case of a 62-year-old male who presented with right upper quadrant and flank pain. Physical examination revealed a fullness of the right upper quadrant. Both computed tomography and magnetic resonance imaging suggested a hemangioma originating from the liver. During angiography with the intent of embolization, it was discovered that the vascular supply was consistent with an adrenal mass rather than a hepatic origin. The patient was referred to Urology and underwent curative right open adrenalectomy and nephrectomy. Histopathology confirmed the diagnosis of an adrenal cavernous hemangioma.

In this grant report, we describe our project to expand measurement-based psychiatric care across 6 early psychosis treatment teams in Minnesota, and to provide a neuroscience-informed cognitive training and motivation enhancement program for individuals with early psychosis. This project is part of the NIMH Early Psychosis Intervention Network (EPINET) initiative which seeks to link data from treatment centers nationally that offer evidence-based specialty care to persons experiencing early psychosis. Systematic analyses of pooled data collected in EPINET will help inform methods for early psychosis care, psychosis risk factors, and pre-emptive interventions. As part of the national EPINET, our hub (Early Psychosis Intervention-Minnesota, EPI-MINN), will: (1) provide measurement-based care in coordinated specialty care programs for early psychosis, (2) determine whether a structured feedback report provides benefit to stakeholders-service users, family members, and primary clinicians, and (3) explore whether deficits in cognition and motivated behavior-two domains that significantly impact functioning and overall quality of life in early psychosis-can be addressed as key treatment goals by implementing a 12-week mobile intervention. Using a regression discontinuity design, participants will be randomized to the cognitive training and motivational enhancement intervention or to treatment as usual. The intervention consists of neuroscience-informed, computerized auditory and social cognitive training exercises, as well as a mobile app where participants interact with each other and with a motivational coach. Participants will complete assessments at 4 time points: baseline and post-intervention (i.e., at 6 months), and again at 12 and 18 months to test the long-term effects of the intervention. All assessments and interventions in this project can be completed entirely remotely., Competing Interests: CONFLICTS OF INTEREST The authors declare they have no conflicts of interest.