TNFR1-mediated senescence and lack of TNFR2-signaling limit human intervertebral disc cell repair in back pain conditions.

Poor intervertebral disc (IVD) healing causes IVD degeneration (IVDD) and progression to herniation and back pain. This study identified distinct roles of TNFα-receptors (TNFRs) in contributing to poor healing in painful IVDD. We first isolated IVDD tissue of back pain subjects and determined the complex pro-inflammatory mixture contained many chemokines for recruiting inflammatory cells.

Surgery for Crohn's Disease Is Associated With a Dysbiotic Microbiome and Metabolome: Results From Two Prospective Cohorts.

Background & Aims: Crohn's disease is associated with alterations in the gut microbiome and metabolome described as dysbiosis. We characterized the microbial and metabolic consequences of ileal resection, the most common Crohn's disease surgery.

Methods: Patients with and without intestinal resection were identified from the Diet to Induce Remission in Crohn's Disease and Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease studies.

Preservation of conjugated primary bile acids by oxygenation of the small intestinal microbiota .

Unlabelled: Bile acids play a critical role in the emulsification of dietary lipids, a critical step in the primary function of the small intestine, which is the digestion and absorption of food. Primary bile acids delivered into the small intestine are conjugated to enhance functionality, in part, by increasing aqueous solubility and preventing passive diffusion of bile acids out of the gut lumen. Bile acid function can be disrupted by the gut microbiota via the deconjugation of primary bile acids by bile salt hydrolases (BSHs), leading to their conversion into secondary bile acids through the expression of bacterial bile acid-inducible genes, a process often observed in malabsorption due to small intestinal bacterial overgrowth.

School Meals for All: A Qualitative Study Exploring Lessons in Successful Advocacy and Policymaking in Maine and California.

Background: The COVID-19 pandemic focused national attention on food insecurity, equity, and the role of school meal programs in supporting children, families, and communities. In doing so, the pandemic created a rare policy window-an opportunity to advance a longstanding public health goal of guaranteed access to free school meals for all students. In July 2021, California and Maine became the first states to authorize school meal for all legislation (also known as universal free meals).

Energy-Efficient Neuromorphic Architectures for Nuclear Radiation Detection Applications.

A comprehensive analysis and simulation of two memristor-based neuromorphic architectures for nuclear radiation detection is presented. Both scalable architectures retrofit a locally competitive algorithm to solve overcomplete sparse approximation problems by harnessing memristor crossbar execution of vector-matrix multiplications. The proposed systems demonstrate excellent accuracy and throughput while consuming minimal energy for radionuclide detection.

Treatment with the apoptosis inhibitor Asunercept reduces clone sizes in patients with lower risk Myelodysplastic Neoplasms.

In low-risk Myelodysplastic Neoplasms (MDS), increased activity of apoptosis-promoting factors such as tumor necrosis factor (TNFα) and pro-apoptotic Fas ligand (CD95L) have been described as possible pathomechanisms leading to impaired erythropoiesis. Asunercept (APG101) is a novel therapeutic fusion protein blocking CD95, which has previously shown partial efficacy in reducing transfusion requirement in a clinical phase I trial for low-risk MDS patients (NCT01736436; 2012-11-26). In the current study we aimed to evaluate the effect of Asunercept therapy on the clonal bone marrow composition to identify potential biomarkers to predict response.

Correction: Antón-García et al. TGFβ1-Induced EMT in the MCF10A Mammary Epithelial Cell Line Model Is Executed Independently of SNAIL1 and ZEB1 but Relies on JUNB-Coordinated Transcriptional Regulation. 2023, , 588.

In the original publication [...

Bacteroides fragilis toxin expression enables lamina propria niche acquisition in the developing mouse gut.

Bacterial toxins are well-studied virulence factors; however, recent studies have revealed their importance in bacterial niche adaptation. Enterotoxigenic Bacteroides fragilis (ETBF) expresses B. fragilis toxin (BFT) that we hypothesized may contribute to both colonic epithelial injury and niche acquisition.

Combining adhesive and nonadhesive injectable hydrogels for intervertebral disc repair in an ovine discectomy model.

Background: Intervertebral disc (IVD) disorders (e.g., herniation) directly contribute to back pain, which is a leading cause of global disability.

LNK/ as a novel driver in juvenile myelomonocytic leukemia.

Mutations in five canonical Ras pathway genes (NF1, NRAS, KRAS, PTPN11 and CBL) are detected in nearly 90% of patients with juvenile myelomonocytic leukemia (JMML), a frequently fatal malignant neoplasm of early childhood. In this report, we describe seven patients diagnosed with SH2B3-mutated JMML, including five patients who were found to have initiating, loss-of-function mutations in the gene. SH2B3 encodes the adaptor protein LNK, a negative regulator of normal hematopoiesis upstream of the Ras pathway.

Understanding the Impacts of Molecular and Macromolecular Crowding Agents on Protein-Polymer Complex Coacervates.

Complex coacervation refers to the liquid-liquid phase separation (LLPS) process occurring between charged macromolecules. The study of complex coacervation is of great interest due to its implications in the formation of membraneless organelles (MLOs) in living cells. However, the impacts of the crowded intracellular environment on the behavior and interactions of biomolecules involved in MLO formation are not fully understood.

Enterobacteriaceae Growth Promotion by Intestinal Acylcarnitines, a Biomarker of Dysbiosis in Inflammatory Bowel Disease.

Background & Aims: Altered plasma acylcarnitine levels are well-known biomarkers for a variety of mitochondrial fatty acid oxidation disorders and can be used as an alternative energy source for the intestinal epithelium when short-chain fatty acids are low. These membrane-permeable fatty acid intermediates are excreted into the gut lumen via bile and are increased in the feces of patients with inflammatory bowel disease (IBD).

Methods: Herein, based on studies in human subjects, animal models, and bacterial cultures, we show a strong positive correlation between fecal carnitine and acylcarnitines and the abundance of Enterobacteriaceae in IBD where they can be consumed by bacteria both in vitro and in vivo.

Lumbar endplate microfracture injury induces Modic-like changes, intervertebral disc degeneration and spinal cord sensitization - an in vivo rat model.

Background Context: Endplate (EP) injury plays critical roles in painful IVD degeneration since Modic changes (MCs) are highly associated with pain. Models of EP microfracture that progress to painful conditions are needed to better understand pathophysiological mechanisms and screen therapeutics.

Purpose: Establish in vivo rat lumbar EP microfracture model and assess crosstalk between IVD, vertebra and spinal cord.

Strategies to Increase Student Participation in School Meals in the United States: A Systematic Review.

Background: School meals play a critical role in promoting child nutrition and advancing equity. An understanding of which evidence-based strategies can increase meal participation is needed to improve student school meal consumption and foodservice finances.

Objective: Our aim was to systematically review the evidence on interventions, initiatives, and policies to increase school meal participation in the United States.

Lumbar endplate microfracture injury induces Modic-like changes, intervertebral disc degeneration and spinal cord sensitization - An In Vivo Rat Model.

: Endplate (EP) injury plays critical roles in painful IVD degeneration since Modic changes (MCs) are highly associated with pain. Models of EP microfracture that progress to painful conditions are needed to better understand pathophysiological mechanisms and screen therapeutics. : Establish in vivo rat lumbar EP microfracture model with painful phenotype.

TGFβ1-Induced EMT in the MCF10A Mammary Epithelial Cell Line Model Is Executed Independently of SNAIL1 and ZEB1 but Relies on JUNB-Coordinated Transcriptional Regulation.

Epithelial-mesenchymal transition (EMT) fosters cancer cell invasion and metastasis, the main cause of cancer-related mortality. Growing evidence that SNAIL and ZEB transcription factors, typically portrayed as master regulators of EMT, may be dispensable for this process, led us to re-investigate its mechanistic underpinnings. For this, we used an unbiased computational approach that integrated time-resolved analyses of chromatin structure and differential gene expression, to predict transcriptional regulators of TGFβ1-inducible EMT in the MCF10A mammary epithelial cell line model.

Transcriptional activity mediated by β-CATENIN and TCF/LEF family members is completely dispensable for survival and propagation of multiple human colorectal cancer cell lines.

Unrestrained transcriptional activity of β-CATENIN and its binding partner TCF7L2 frequently underlies colorectal tumor initiation and is considered an obligatory oncogenic driver throughout intestinal carcinogenesis. Yet, the TCF7L2 gene carries inactivating mutations in about 10% of colorectal tumors and is non-essential in colorectal cancer (CRC) cell lines. To determine whether CRC cells acquire TCF7L2-independence through cancer-specific compensation by other T-cell factor (TCF)/lymphoid enhancer-binding factor (LEF) family members, or rather lose addiction to β-CATENIN/TCF7L2-driven gene expression altogether, we generated multiple CRC cell lines entirely negative for TCF/LEF or β-CATENIN expression.

Postoperative Opioid Use and Prescribing Patterns among Patients Undergoing Cervical Laminectomy with Instrumented Fusion versus Cervical Laminoplasty with Reconstruction.

Study Design: Retrospective cohort study.

Objective: To compare patterns in opioid usage and prescriptions between patients who undergo cervical laminectomy with instrumented fusion (LF) vs cervical laminoplasty with reconstruction (LP) within single surgeon and national database cohorts.

Methods: We identified patients with cervical myelopathy undergoing primary LF or LP in both a single-surgeon series cohort (2004-2018) and a nationally representative cohort drawn from the IBM Marketscan database (2014-2016).

Acute Vertebral Fractures in Skiing and Snowboarding: A 20-Year Sex-Specific Analysis of National Injury Data.

Background: The epidemiology of acute vertebral fractures (AVFs) sustained while skiing and snowboarding remains poorly defined in the United States.

Hypothesis: It was hypothesized that there would be no significant differences across sex and a greater number of AVFs in younger age groups associated with skiing and snowboarding.

Study Design: Descriptive epidemiological study.