Genetically determined body mass index is associated with diffuse large B-cell lymphoma in polygenic and Mendelian randomization analyses.

Obesity has been associated with non-Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome-wide association studies of European ancestry (N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.

Microsatellite Instability, Tumor Mutational Burden, and Response to Immune Checkpoint Blockade in Patients with Prostate Cancer.

Purpose: Patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) and high tumor mutational burden (TMB-H) prostate cancers are candidates for pembrolizumab. We define the genomic features, clinical course, and response to immune checkpoint blockade (ICB) in patients with MSI-H/dMMR and TMB-H prostate cancers without MSI [TMB-H/microsatellite stable (MSS)].

Experimental Design: We sequenced 3,244 tumors from 2,257 patients with prostate cancer.

Targeting HER2-mutant metastatic cervical cancer with neratinib: Final results from the phase 2 SUMMIT basket trial.

Objective: HER2 mutations are associated with poor prognosis and are detected in 3-6% of cervical cancers. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, had activity in several HER2-mutant cancer types in the phase 2 SUMMIT basket study. We present updated and final results from the cervical cancer cohort of SUMMIT.

Role of dietary supplements in the continuous battle against COVID-19.

A sudden outbreak of the COVID-19 pandemic was a big blow to the world community on every level. Created by a novel coronavirus, SARS-CoV-2, which was previously unknown to the human immune system. The expert opinion almost immediately united on the fact that the most effective way of fighting the pandemic would be by building immunity artificially via a mass immunization program.

Assessing the Genomic Landscape of Cervical Cancers: Clinical Opportunities and Therapeutic Targets.

Purpose: Tumor genomic profiling is increasingly used to guide treatment strategy in patients with cancer. We integrated tumor genomic, clinical demographic, and treatment response data to assess how prospective tumor-normal sequencing impacted treatment selection in patients with cervical cancer.

Experimental Design: Cervical cancers were prospectively analyzed using the MSK-IMPACT (Memorial Sloan Kettering Cancer Center - Integrated Mutation Profiling of Actionable Cancer Targets) next-generation sequencing panel.

Calnuc-derived nesfatin-1-like peptide is an activator of tumor cell proliferation and migration.

Calnuc (nucleobindin-1, nucb1) is a Ca -binding protein involved in the etiology of many human diseases. To understand the functions of calnuc, we have identified a nesfatin-1-like peptide (NLP) in its N terminus that is proteolyzed by a convertase enzyme in the secretory granules of cells. Mutational studies confirm the presence of a proteolytic cleavage site for proprotein convertase subtilisin/kexin type 1 (PCSK1).

Characterizing the Impedance Properties of Dry E-Textile Electrodes Based on Contact Force and Perspiration.

Biopotential electrodes play an integral role within smart wearables and clothing in capturing vital signals like electrocardiogram (ECG), electromyogram (EMG), and electroencephalogram (EEG). This study focuses on dry e-textile electrodes (E1-E6) and a laser-cut knit electrode (E7), to assess their impedance characteristics under varying contact forces and moisture conditions. Synthetic perspiration was applied using a moisture management tester and impedance was measured before and after exposure, followed by a 24 h controlled drying period.

Clinical and Molecular Features of Long-term Response to Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer.

Purpose: We sought to identify features of patients with advanced non-small cell lung cancer (NSCLC) who achieve long-term response (LTR) to immune checkpoint inhibitors (ICI), and how these might differ from features predictive of short-term response (STR).

Experimental Design: We performed a multicenter retrospective analysis of patients with advanced NSCLC treated with ICIs between 2011 and 2022. LTR and STR were defined as response ≥ 24 months and response < 12 months, respectively.

Prevalence and Clinical Implications of Mismatch Repair-Proficient Colorectal Cancer in Patients With Lynch Syndrome.

Purpose: Lynch syndrome (LS)-associated colorectal cancer (CRC) is characterized by mismatch repair-deficiency (MMR-D) and/or microsatellite instability (MSI). However, with increasing utilization of germline testing, MMR-proficient (MMR-P) and/or microsatellite stable (MSS) CRC has also been observed. We sought to characterize MMR-P/MSS CRC among patients with LS.

iTex Gloves: Design and In-Home Evaluation of an E-Textile Glove System for Tele-Assessment of Parkinson's Disease.

Parkinson's disease (PD) is a neurological progressive movement disorder, affecting more than 10 million people globally. PD demands a longitudinal assessment of symptoms to monitor the disease progression and manage the treatments. Existing assessment methods require patients with PD (PwPD) to visit a clinic every 3-6 months to perform movement assessments conducted by trained clinicians.

Textile Knitted Stretch Sensors for Wearable Health Monitoring: Design and Performance Evaluation.

The advancement of smart textiles has led to significant interest in developing wearable textile sensors (WTS) and offering new modalities to sense vital signs and activity monitoring in daily life settings. For this, textile fabrication methods such as knitting, weaving, embroidery, and braiding offer promising pathways toward unobtrusive and seamless sensing for WTS applications. Specifically, the knitted sensor has a unique intermeshing loop structure which is currently used to monitor repetitive body movements such as breathing (microscale motion) and walking (macroscale motion).

NBN Pathogenic Germline Variants are Associated with Pan-Cancer Susceptibility and In Vitro DNA Damage Response Defects.

Purpose: To explore the role of NBN as a pan-cancer susceptibility gene.

Experimental Design: Matched germline and somatic DNA samples from 34,046 patients were sequenced using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets and presumed pathogenic germline variants (PGV) identified. Allele-specific and gene-centered analysis of enrichment was conducted and a validation cohort of 26,407 pan-cancer patients was analyzed.

Multiple Primary Cancers in Patients Undergoing Tumor-Normal Sequencing Define Novel Associations.

Background: Cancer survivors are developing more subsequent tumors. We sought to characterize patients with multiple (≥2) primary cancers (MPC) to assess associations and genetic mechanisms.

Methods: Patients were prospectively consented (01/2013-02/2019) to tumor-normal sequencing via a custom targeted panel (MSK-IMPACT).

An E-Textile Respiration Sensing System for NICU Monitoring: Design and Validation.

The world is witnessing a rising number of preterm infants who are at significant risk of medical conditions. These infants require continuous care in Neonatal Intensive Care Units (NICU). Medical parameters are continuously monitored in premature infants in the NICU using a set of wired, sticky electrodes attached to the body.

Small peptide inhibitor from the sequence of RUNX3 disrupts PAK1-RUNX3 interaction and abrogates its phosphorylation-dependent oncogenic function.

P21 Activated Kinase 1 (PAK1) is an oncogenic serine/threonine kinase known to play a significant role in the regulation of cytoskeleton and cell morphology. Runt-related transcription factor 3 (RUNX3) was initially known for its tumor suppressor function, but recent studies have reported the oncogenic role of RUNX3 in various cancers. Previous findings from our laboratory provided evidence that Threonine 209 phosphorylation of RUNX3 acts as a molecular switch in dictating the tissue-specific dualistic functions of RUNX3 for the first time.

Prevalence of Germline Alterations on Targeted Tumor-Normal Sequencing of Esophagogastric Cancer.

Importance: Among patients with esophagogastric cancers, only individuals who present with known features of heritable cancer syndromes are referred for genetic testing. Broader testing might identify additional patients with germline alterations.

Objectives: To examine the prevalence of likely pathogenic or pathogenic (LP/P) germline alterations among patients with esophagogastric cancer and to assess associations between germline variant prevalence and demographic and clinicopathologic features.

Aberrant environment and PS-binding to calnuc C-terminal tail drives exosomal packaging and its metastatic ability.

The characteristic features of cancer cells are aberrant (acidic) intracellular pH and elevated levels of phosphatidylserine. The primary focus of cancer research is concentrated on the discovery of biomarkers directed towards early diagnosis and therapy. It has been observed that azoxymethane-treated mice demonstrate an increased expression of calnuc (a multi-domain, Ca2+- and DNA-binding protein) in their colon, suggesting it to be a good biomarker of carcinogenesis.

Targeting Germline- and Tumor-Associated Nucleotide Excision Repair Defects in Cancer.

Purpose: Nucleotide excision repair (NER) gene alterations constitute potential cancer therapeutic targets. We explored the prevalence of NER gene alterations across cancers and putative therapeutic strategies targeting these vulnerabilities.

Experimental Design: We interrogated our institutional dataset with mutational data from more than 40,000 patients with cancer to assess the frequency of putative deleterious alterations in four key NER genes.

Mutation Rates in Cancer Susceptibility Genes in Patients With Breast Cancer With Multiple Primary Cancers.

Purpose: Women with breast cancer have a 4%-16% lifetime risk of a second primary cancer. Whether mutations in genes other than are enriched in patients with breast and another primary cancer over those with a single breast cancer (S-BC) is unknown.

Patients And Methods: We identified pathogenic germline mutations in 17 cancer susceptibility genes in patients with -negative breast cancer in 2 different cohorts: cohort 1, high-risk breast cancer program (multiple primary breast cancer [MP-BC], n = 551; S-BC, n = 449) and cohort 2, familial breast cancer research study (MP-BC, n = 340; S-BC, n = 1,464).

A Change in Domain Cooperativity Drives the Function of Calnuc.

With the increasing incidence of neurodegenerative disorders, there is an urgent need to understand the protein folding process. Examining the folding process of multidomain proteins remains a prime challenge, as their complex conformational dynamics make them highly susceptible to misfolding and/or aggregation. The presence of multiple domains in a protein can lead to interaction between the partially folded domains, thereby driving misfolding and/or aggregation.

Genetically Determined Height and Risk of Non-hodgkin Lymphoma.

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry.

RespNet: A deep learning model for extraction of respiration from photoplethysmogram.

Respiratory ailments afflict a wide range of people and manifests itself through conditions like asthma and sleep apnea. Continuous monitoring of chronic respiratory ailments is seldom used outside the intensive care ward due to the large size and cost of the monitoring system. While Electrocardiogram (ECG) based respiration extraction is a validated approach, its adoption is limited by access to a suitable continuous ECG monitor.