Developing Topics.

Background: Cytoplasmic inclusions of TDP-43 are the primary pathology in the majority of ALS and FTLD cases. Recent reports in cell and animal models suggest TDP-43 pathology may enhance neuronal excitability, which could contribute to neurodegeneration via excitotoxicity. Dox-regulatable rNLS8 mice express human TDP-43 with mutations in the nuclear localization signal (hTDP-43NLSm) to promote cytoplasmic accumulation.

A Narrative Review of Old and Emerging Treatment Modalities for Substance Use Disorders.

Substance use disorders (SUDs) represent one of the leading causes of preventable death in the setting of overdose and comorbidities leading to mortality. A multi-database literature search limited to peer-reviewed articles within the last 10 years was conducted to compare treatment modalities used to treat SUDs. This literature review aims to provide a concise yet comprehensive summary of the various treatment modalities that exist to address these disorders in clinical practice.

An Infant With Variant: A Novel Etiology of 46,XY DSD and Literature Review.

46,XY sex reversal 11 (SRXY11) is a rare and recently identified form of 46,XY difference in sexual development (DSD), caused by variants in the DEAH-Box Helicase 37 gene (). is crucial for ribosome biogenesis, but its specific role in gonadal development remains unclear. The genital phenotype varies widely, ranging from typical female to typical male.

Single-cell multi-omic analysis of fibrolamellar carcinoma reveals rewired cell-to-cell communication patterns and unique vulnerabilities.

Fibrolamellar carcinoma (FLC) is a rare malignancy disproportionately affecting adolescents and young adults with no standard of care. FLC is characterized by thick stroma, which has long suggested an important role of the tumor microenvironment. Over the past decade, several studies have revealed aberrant markers and pathways in FLC.

A phase 2 study of frontline pembrolizumab in follicular lymphoma.

Background: The tumor microenvironment (TME), including infiltrating T-cells, is thought to play a major role in the pathogenesis and prognosis of follicular lymphoma (FL) and may contribute to its widely varied disease course. We hypothesized that programmed death-1 inhibition may be most effective in untreated, immunocompetent FL patients. Thus, we developed a phase 2 study to evaluate the efficacy of pembrolizumab as the initial treatment for indolent B-cell lymphoma.

Association among diabetes, cardiovascular disease and mortality in patients hospitalised for COVID-19: an analysis of the American Heart Association COVID-19 CVD Registry.

Objective: To examine inpatient COVID-19-related outcomes among patients with and without diabetes alone or with a history of established heart failure (HF) or established atherosclerotic cardiovascular disease (ASCVD).

Design: Observational study; longitudinal analysis of registry data.

Setting: Hospitals in the USA reporting to the American Heart Association (AHA) COVID-19 Registry from January 2020 to May 2021.

Traffic Patterns and Emergency Medical Services Prenotification Transport Estimates in Trauma Activations.

Objective: To determine whether traffic patterns affect the accuracy of emergency medical services (EMS) prediction of transport interval to the emergency department (ED).

Methods: Using a retrospective study, we examined all trauma activations at a level one, urban trauma center in Manhasset, New York, between 5/22/2021 and 3/30/2022. Inclusion criteria included patients ≥18 years and arrival by EMS.

Toll-like receptor signaling in neurons modulates C. elegans feeding behavior in a hunger state-dependent manner.

Animals face the risk of encountering pathogenic microbes while foraging for resources. Assessing the risk of nutrition vs. infection can result in the behavioral regulation of immune processes.

Real World Outcomes with Treatment Free Remission in Chronic Myeloid Leukemia-Experience from a Tertiary Care Cancer Centre.

Chronic myeloid leukaemia (CML) is caused by balanced translocation t(9::22)(q34;q11) resulting in formation of pathogenic BCR-ABL fusion gene. Tyrosine kinase inhibitors (TKI) have revolutionised the treatment of CML. Ongoing treatment with TKI leads to side effects and has financial impact.

Where Do Plasma Biomarkers fit in With Current Alzheimer's Disease Detection?

Objectives: We examine the clinical utility of plasma-based detection for Alzheimer's disease (AD) pathophysiology in older adults with mild cognitive impairment (MCI) and whether cognitive screening can inform when to use plasma-based AD tests.

Methods: Seventy-four community-dwelling older adults with MCI had testing with plasma phosphorylated tau (p-tau) 217 and 181, positron emission tomography (PET) imaging for amyloid beta (Aβ), and cognitive assessment. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of plasma p-tau.

Adjuvant treatments for recurrent respiratory papillomatosis: a descriptive review and proposed management guideline in adults.

Objective: Recurrent respiratory papillomatosis is a rare disease characterised by growth of papilloma within the respiratory tract. The disease course is variable but can require frequent surgical interventions alongside adjuvant medical treatments. There is no definitive curative treatment or gold-standard guidelines for management.

A randomized, double-blind, placebo-controlled trial of weight loss using liraglutide 3.0 mg for weight recurrence after Roux-en-Y gastric bypass.

Background: Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB) remains the gold standard for treating obesity. Most people regain weight from postsurgery nadir.

Objectives: Liraglutide 3.

Hyperexcitability precedes CA3 hippocampal neurodegeneration in a dox-regulatable TDP-43 mouse model of ALS-FTD.

Unlabelled: Neuronal hyperexcitability is a hallmark of amyotrophic lateral sclerosis (ALS) but its relationship with the TDP-43 aggregates that comprise the predominant pathology in over 90% of ALS cases remains unclear. Emerging evidence in tissue and slice culture models indicate that TDP-43 pathology induces neuronal hyperexcitability suggesting it may be responsible for the excitotoxicity long believed to be a major driver of ALS neuron death. Here, we characterized hyperexcitability and neurodegeneration in the hippocampus of doxycycline-regulatable rNLS8 mice (NEFH-tTA x tetO-hTDP-43ΔNLS), followed by treatment with AAV encoded DREADDs and anti-seizure medications to measure the effect on behavioral function and neurodegeneration.

Microfluidic Modulation of Microvasculature in Microdissected Tumors.

The microvasculature within the tumor microenvironment (TME) plays an essential role in cancer signaling beyond nutrient delivery. However, it has been challenging to control the generation and/or maintenance of microvasculature in systems, a critical step for establishing cancer models of high clinical biomimicry. There have been great successes in engineering tissues incorporating microvasculature (.

DNAJB1-PRKACA fusion drives fibrolamellar liver cancer through impaired SIK signaling and CRTC2/p300-mediated transcriptional reprogramming.

Fibrolamellar carcinoma (FLC) is a liver cancer of adolescents and young adults characterized by fusions of the genes encoding the protein kinase A catalytic subunit, PRKACA, and heat shock protein, DNAJB1. The chimeric DNAJB1-PRKACA protein has increased kinase activity and is essential for FLC xenograft growth. Here, we explore the critical oncogenic pathways controlled by DNAJB1-PRKACA using patient-derived FLC models, engineered systems, and patient samples.

Label-free, real-time monitoring of cytochrome C drug responses in microdissected tumor biopsies with a multi-well aptasensor platform.

Functional assays on intact tumor biopsies can complement genomics-based approaches for precision oncology, drug testing, and organs-on-chips cancer disease models by capturing key therapeutic response determinants, such as tissue architecture, tumor heterogeneity, and the tumor microenvironment. Most of these assays rely on fluorescent labeling, a semiquantitative method best suited for single-time-point assays or labor-intensive immunostaining analysis. Here, we report integrated aptamer electrochemical sensors for on-chip, real-time monitoring of cytochrome C, a cell death indicator, from intact microdissected tissues with high affinity and specificity.

Proteo-metabolomics and patient tumor slice experiments point to amino acid centrality for rewired mitochondria in fibrolamellar carcinoma.

Fibrolamellar carcinoma (FLC) is a rare, lethal, early-onset liver cancer with a critical need for new therapeutics. The primary driver in FLC is the fusion oncoprotein, DNAJ-PKAc, which remains challenging to target therapeutically. It is critical, therefore, to expand understanding of the FLC molecular landscape to identify druggable pathways/targets.

Cohort profile: study design and baseline characteristics of an observational longitudinal weight loss cohort and biorepository of patients undergoing sleeve gastrectomy in the USA.

Purpose: We developed a comprehensive sleeve gastrectomy (SG) weight loss study cohort and biorepository to uncover mechanisms, biomarkers and predictive factors of weight loss, weight maintenance and amelioration of obesity-related comorbidities. For this purpose, we collected psychosocial, anthropometric, clinical data and a variety of samples pre-surgery, intraoperatively and 1.5, 3, 12 and 24 months post-surgery.

Obesogenic Medication Use in End-Stage Kidney Disease and Association With Transplant Listing.

Objectives: Obesogenic medications are a putative contributor to the obesity epidemic. While 20% of adults take ≥1 obesogenic medication, the proportion in the end-stage kidney disease (ESKD) population-a group enriched for cardiometabolic complications-is unknown. Obesogenic medications may contribute to obesity and hamper weight loss efforts to achieve transplant listing.

Hospital charges for laparoscopic sleeve gastrectomy compared to robotic sleeve gastrectomy: a multicenter study.

Background: Sleeve gastrectomy has become a gold standard in addressing medically refractory obesity. Robotic platforms are becoming more utilized, however, data on its cost-effectiveness compared to laparoscopy remain controversial (1-3). At NYU Langone Health, many of the bariatric surgeons adopted robotic surgery as part of their practices starting in 2021.