Leveraging cancer mutation data to inform the pathogenicity classification of germline missense variants.

Innovative and easy-to-implement strategies are needed to improve the pathogenicity assessment of rare germline missense variants. Somatic cancer driver mutations identified through large-scale tumor sequencing studies often impact genes that are also associated with rare Mendelian disorders. The use of cancer mutation data to aid in the interpretation of germline missense variants, regardless of whether the gene is associated with a hereditary cancer predisposition syndrome or a non-cancer-related developmental disorder, has not been systematically assessed.

Recommendations for the optimization of student led free vision screening programs.

Purpose: To report the summary characteristics of operational models associated with Student Led Free Vision Screening Programs (SLFVSP) and to identify opportunities for program optimization.

Methods: An 81-question mixed methods survey was distributed to SLFVSP leaders nationwide and Medical Student Educators within the American University Ophthalmology Professors (AUPO) Association. Survey responses were analyzed using Mann Whitney U and Fisher's Exact tests.

Impact of Reach Height on Estimated Rotator Cuff Compression Risk in Manual Wheelchair Users With Spinal Cord Injury.

Reaching is a common daily activity requiring a range of humeral elevation that contributes to rotator cuff compression. The purpose of this study was to estimate supraspinatus and infraspinatus tendon compression risk relative to the acromion and coracoacromial ligament during reaching by manual wheelchair users with spinal cord injury. A cross-sectional design was used to evaluate 8 participants (7 males, median [range] age 36 y [23-61]).

Dr. John R. Phillips: Nurse Scholar Extraordinaire.

Scholarship is an important topic for the continuation of the discipline of nursing. has asked Dr. John R.

MGA-related syndrome: A proposed novel disorder.

MGA (OMIM: 616061) encodes a dual-specificity transcription factor that regulates the expression of Max-network and T-box family target genes, important in embryogenesis. Previous studies have linked MGA to various phenotypes, including neurodevelopmental disorders, congenital heart disease, and early-onset Parkinson's disease. Here, we describe the clinical phenotype of individuals with de novo, heterozygous predicted loss-of-function variants in MGA, suggesting a unique disorder involving both neurodevelopmental and congenital anomalies.

Nodal Burden and Oncologic Outcomes in Patients With Residual Isolated Tumor Cells After Neoadjuvant Chemotherapy (ypN0i+): The OPBC-05/ICARO Study.

Purpose: The nodal burden of patients with residual isolated tumor cells (ITCs) in the sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) (ypN0i+) is unknown, and axillary management is not standardized. We investigated rates of additional positive lymph nodes (LNs) at axillary lymph node dissection (ALND) and oncologic outcomes in patients with ypN0i+ treated with and without ALND.

Methods: The Oncoplastic Breast Consortium-05/ICARO cohort study (ClinicalTrials.

Monoallelic loss-of-function variants in GSK3B lead to autism and developmental delay.

De novo variants adjacent to the canonical splicing sites or in the well-defined splicing-related regions are more likely to impair splicing but remain under-investigated in autism spectrum disorder (ASD). By analyzing large, recent ASD genome sequencing cohorts, we find a significant burden of de novo potential splicing-disrupting variants (PSDVs) in 5048 probands compared to 4090 unaffected siblings. We identified 55 genes with recurrent de novo PSDVs that were highly intolerant to variation.

Extensive Invasive Sinusitis Secondary to Infection.

Invasive sinusitis is a rare complication of sinusitis. We present the case of a woman, age 72 years, who presented with acute encephalopathy in the setting of sepsis found to have extensive invasive sinusitis with intracranial extension secondary to , managed with intravenous antibiotics alone. is a rare cause of acute bacterial sinusitis, associated with infections of relatively greater severity and risk of intracranial spread, often requiring a combination of intravenous antibiotics and surgical debridement for source control.

Discordance of human epidermal growth factor receptor 2-low status between breast primary and distant metastases with clinical-pathological correlation.

Aims: Breast cancer with human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 1+ or 2+ with negative in-situ hybridisation (ISH) (HER2-low) can now be targeted by HER2 antibody drug conjugates. We set out to compare HER2 status between matched primary invasive breast carcinoma (IBC) and distant metastases (DM) with clinical-pathological correlation, with specific interest in HER2-low.

Methods: Biomarker studies and clinical-pathological features of primary IBC with matched DM diagnosed between 2021 and 2022 were retrospectively analysed.

Karen J. Foli: A Nurse Scholar With an Unconventional Trajectory.

Nurse scholar Karen J. Foli has had an unconventional trajectory. She has written everything from mysteries to thrillers to peer-reviewed journal manuscripts and Food and Drug Administration documents.

Management of Ipsilateral Breast Tumor Recurrence Following Breast Conservation Surgery for Ductal Carcinoma In Situ: A Data-Poor Zone.

Background: Breast conserving surgery (BCS) is well established for the management of ductal carcinoma in situ (DCIS), but neither randomized trials nor guidelines address management of ipsilateral breast tumor recurrence (IBTR) after BCS for DCIS.

Patients And Methods: We identified women treated with BCS for DCIS who developed IBTR as a first event. Between those treated with mastectomy versus re-BCS, we compare the clinicopathologic characteristics, the use of adjuvant radiotherapy (RT) both upfront ("primary RT") and post IBTR ("secondary RT"), of tamoxifen, the rate of third events (local, regional, distant), and both breast cancer specific (BCSS) and overall survival (OS).

Inferring disease course from differential exon usage in the wide titinopathy spectrum.

Objective: Biallelic titin truncating variants (TTNtv) have been associated with a wide phenotypic spectrum, ranging from complex prenatal muscle diseases with dysmorphic features to adult-onset limb-girdle muscular dystrophy, with or without cardiac involvement. Given the size and complexity of TTN, reaching an unequivocal molecular diagnosis and precise disease prognosis remains challenging.

Methods: In this case series, 12 unpublished cases and one already published case with biallelic TTNtv were collected from multiple international medical centers between November 2022 and September 2023.

Breast-Conserving Therapy Versus Postmastectomy Breast Reconstruction: Propensity Score-Matched Analysis.

Background: Although studies have compared patient-reported outcomes (PROs) after breast conserving-therapy (BCT) and postmastectomy breast reconstruction (PMBR), they often have been confounded by treatment or other factors that complicate a direct comparison. This study aimed to compare PROs after BCT and PMBR by using propensity score-matching analysis.

Methods: Patients who underwent BCT or PMBR between 2010 and 2022 and completed the BREAST-Q were identified.

Pathologic complete response after neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers.

BRCA1 and BRCA2 pathogenic variant carriers develop breast cancers with distinct pathological characteristics and mutational signatures that may result in differential response to chemotherapy. We compared rates of pathologic complete response (pCR) after NAC between BRCA1/2 variant carriers and noncarriers in a cohort of 1426 women (92 [6.5%] BRCA1 and 73 [5.

Effectiveness of smoking cessation interventions among adults: an overview of systematic reviews.

Background: This overview of reviews aims to identify evidence on the benefits (i.e. tobacco use abstinence and reduction in smoking frequency) and harms (i.

IFNγ Production by Functionally Reprogrammed Tregs Promotes Antitumor Efficacy of OX40/CD137 Bispecific Agonist Therapy.

Unlabelled: Regulatory T cells (Treg) are highly enriched within many tumors and suppress immune responses to cancer. There is intense interest in reprogramming Tregs to contribute to antitumor immunity. OX40 and CD137 are expressed highly on Tregs, activated and memory T cells, and NK cells.