Mortality of gastrointestinal cancers attributable to smoking, alcohol, and metabolic risk factors, and its association with socioeconomic development status 2000-2021: GI Cancer Mortality and Risk Factors.

Objective: Gastrointestinal (GI) cancers account for one-third of global cancer mortality, with nearly half being preventable. This study updates the global burden of GI cancers attributed to major risk factors: smoking, alcohol, and metabolic disturbances.

Methods: We utilized data from the Global Burden of Disease Study 2021 to examine trends in death and age-standardized death rates related to GI cancers caused by smoking, alcohol, high body mass index (BMI), and high fasting blood glucose (FBG) from 2000 to 2021.

A Novel Crosslinking Approach for Biomanufacturing of a Collagen-Based Skin Dermal Template.

Third-degree burns result in extensive damage to the skin's epidermal and dermal layers, with limited treatment options available. Currently, xenogeneic collagen-based skin grafts are used as scaffolds to integrate into the wound bed and provide a template for neodermis formation. Existing commercial products like Integra dermal templates rely on a time-consuming and variable dehydrothermal (DHT) crosslinking process.

A simplified geriatric prognostic index to survival in older Asian patients with diffuse large B-Cell lymphoma treated with standard chemo-immunotherapy.

While there are many proposed clinical prediction models for diffuse large B-cell lymphoma, like the International Prognostic Index (IPI), revised IPI and the National Comprehensive Cancer Network IPI, there is no widely used model for older patients. A recent study proposed a Geriatric Prognostic Index (GPI) validated in a Norwegian cohort, using independent predictors involving demographic, biochemical and functional parameters. This study aims to validate the GPI in an Asian cohort and simplify the GPI for ease of clinical application.

Real-world outcomes of diffuse large B-cell lymphoma treated with frontline R-CHOP(-like) regimens in an Asian multi-ethnic population.

Background: Recent breakthrough advances in the treatment of DLBCL, such as the antibody-drug conjugate polatuzumab vedotin, have yielded clinical survival benefit over rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for the first time in 20 years since the advent of the rituximab era. We thus examine the outcomes of standard immunochemotherapy for DLBCL in our multi-ethnic Asian population, so as to determine the real-world clinical need to adopt new therapeutics in this disease entity.

Methods: We conducted a retrospective study involving patients (n = 1071) diagnosed with DLBCL at the National Cancer Centre Singapore from 2010 to 2022, and treated with first-line rituximab-based regimens.

Liver cancer in 2021: Global burden of disease study.

Background & Aims: The epidemiology of adult primary liver cancer continues to evolve, owing to the increasing prevalence of metabolic disease, rising alcohol consumption, advances in vaccination for HBV, and antiviral therapy for HCV. Disparities in care and the burden of liver cancer between populations persist. We assess trends in the burden of liver cancer and contributions by various etiologies across 204 countries and territories from 2010 to 2021.

Huntingtin contains an ubiquitin-binding domain and regulates lysosomal targeting of mitochondrial and RNA-binding proteins.

Understanding the normal function of the Huntingtin (HTT) protein is of significance in the design and implementation of therapeutic strategies for Huntington's disease (HD). Expansion of the CAG repeat in the gene, encoding an expanded polyglutamine (polyQ) repeat within the HTT protein, causes HD and may compromise HTT's normal activity contributing to HD pathology. Here, we investigated the previously defined role of HTT in autophagy specifically through studying HTT's association with ubiquitin.

Latest Advances in Chondrocyte-Based Cartilage Repair.

Chondrocyte-based cell therapy has been used for more than 30 years and is still considered to be a promising method of cartilage repair despite some limitations. This review introduces the latest developments of four generations of autologous chondrocyte implantation and current autologous chondrocyte products. The regeneration of cartilage from adult chondrocytes is limited by culture-induced dedifferentiation and patient age.

Identifying dysregulated regions in amyotrophic lateral sclerosis through chromatin accessibility outliers.

The high heritability of amyotrophic lateral sclerosis (ALS) contrasts with its low molecular diagnosis rate post-genetic testing, pointing to potential undiscovered genetic factors. To aid the exploration of these factors, we introduced EpiOut, an algorithm to identify chromatin accessibility outliers that are regions exhibiting divergent accessibility from the population baseline in a single or few samples. Annotation of accessible regions with histone chromatin immunoprecipitation sequencing and Hi-C indicates that outliers are concentrated in functional loci, especially among promoters interacting with active enhancers.

Chemical and Electrochemical Characterization of Hot-Pressed LiPSCl Solid State Electrolyte: Operating Pressure-Invariant High Ionic Conductivity.

Sulfide solid state electrolytes (SSE) are among the most promising materials in the effort to replace liquid electrolytes, largely due to their comparable ionic conductivities. Among the sulfide SSEs, Argyrodites (LiPSX, X=Cl, Br, I) further stand out due to their high theoretical ionic conductivity (~1×10 S cm) and interfacial stability against reactive metal anodes such as lithium. Generally, solid state electrolyte pellets are pressed from powder feedstock at room temperature, however, pellets fabricated by cold pressing consistently result in low bulk density and high porosity, facilitating interfacial degradation reactions and allowing dendrites to propagate through the pores and grain boundaries.

Simultaneous detection of pathogens and antimicrobial resistance genes with the open source, cloud-based, CZ ID pipeline.

Antimicrobial resistant (AMR) pathogens represent urgent threats to human health, and their surveillance is of paramount importance. Metagenomic next generation sequencing (mNGS) has revolutionized such efforts, but remains challenging due to the lack of open-access bioinformatics tools capable of simultaneously analyzing both microbial and AMR gene sequences. To address this need, we developed the CZ ID AMR module, an open-access, cloud-based workflow designed to integrate detection of both microbes and AMR genes in mNGS and whole-genome sequencing (WGS) data.

Simultaneous detection of pathogens and antimicrobial resistance genes with the open source, cloud-based, CZ ID pipeline.

Antimicrobial resistant (AMR) pathogens represent urgent threats to human health, and their surveillance is of paramount importance. Metagenomic next generation sequencing (mNGS) has revolutionized such efforts, but remains challenging due to the lack of open-access bioinformatics tools capable of simultaneously analyzing both microbial and AMR gene sequences. To address this need, we developed the Chan Zuckerberg ID (CZ ID) AMR module, an open-access, cloud-based workflow designed to integrate detection of both microbes and AMR genes in mNGS and whole-genome sequencing (WGS) data.

Transplanted human neural stem cells rescue phenotypes in zQ175 Huntington's disease mice and innervate the striatum.

Huntington's disease (HD), a genetic neurodegenerative disorder, primarily affects the striatum and cortex with progressive loss of medium-sized spiny neurons (MSNs) and pyramidal neurons, disrupting cortico-striatal circuitry. A promising regenerative therapeutic strategy of transplanting human neural stem cells (hNSCs) is challenged by the need for long-term functional integration. We previously described that, with short-term hNSC transplantation into the striatum of HD R6/2 mice, human cells differentiated into electrophysiologically active immature neurons, improving behavior and biochemical deficits.

Human Mesenchymal Stem Cell Processing for Clinical Applications Using a Closed Semi-Automated Workflow.

Human mesenchymal stem cells (hMSCs) are currently being explored as a promising cell-based therapeutic modality for various diseases, with more market approvals for clinical use expected over the next few years. To facilitate this transition, addressing the bottlenecks of scale, lot-to-lot reproducibility, cost, regulatory compliance, and quality control is critical. These challenges can be addressed by closing the process and adopting automated manufacturing platforms.

Large-scale differentiation of iPSC-derived motor neurons from ALS and control subjects.

Using induced pluripotent stem cells (iPSCs) to understand the mechanisms of neurological disease holds great promise; however, there is a lack of well-curated lines from a large array of participants. Answer ALS has generated over 1,000 iPSC lines from control and amyotrophic lateral sclerosis (ALS) patients along with clinical and whole-genome sequencing data. The current report summarizes cell marker and gene expression in motor neuron cultures derived from 92 healthy control and 341 ALS participants using a 32-day differentiation protocol.

Single-nuclei transcriptome analysis of Huntington disease iPSC and mouse astrocytes implicates maturation and functional deficits.

Huntington disease (HD) is a neurodegenerative disorder caused by expanded CAG repeats in the huntingtin gene that alters cellular homeostasis, particularly in the striatum and cortex. Astrocyte signaling that establishes and maintains neuronal functions are often altered under pathological conditions. We performed single-nuclei RNA-sequencing on human HD patient-induced pluripotent stem cell (iPSC)-derived astrocytes and on striatal and cortical tissue from R6/2 HD mice to investigate high-resolution HD astrocyte cell state transitions.

An altered extracellular matrix-integrin interface contributes to Huntington's disease-associated CNS dysfunction in glial and vascular cells.

Astrocytes and brain endothelial cells are components of the neurovascular unit that comprises the blood-brain barrier (BBB) and their dysfunction contributes to pathogenesis in Huntington's disease (HD). Defining the contribution of these cells to disease can inform cell-type-specific effects and uncover new disease-modifying therapeutic targets. These cells express integrin (ITG) adhesion receptors that anchor the cells to the extracellular matrix (ECM) to maintain the integrity of the BBB.

Huntington disease oligodendrocyte maturation deficits revealed by single-nucleus RNAseq are rescued by thiamine-biotin supplementation.

The complexity of affected brain regions and cell types is a challenge for Huntington's disease (HD) treatment. Here we use single nucleus RNA sequencing to investigate molecular pathology in the cortex and striatum from R6/2 mice and human HD post-mortem tissue. We identify cell type-specific and -agnostic signatures suggesting oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs) are arrested in intermediate maturation states.

Mechanotransduction through adhesion molecules: Emerging roles in regulating the stem cell niche.

Stem cells have been shown to play an important role in regenerative medicine due to their proliferative and differentiation potential. The challenge, however, lies in regulating and controlling their potential for this purpose. Stem cells are regulated by growth factors as well as an array of biochemical and mechanical signals.

Pediatric hand fractures detection on radiographs: do localization cues improve diagnostic performance?

Objective: To compare the diagnostic accuracy and interpretation time for detection of pediatric fractures on hand radiographs with and without localization cues.

Materials And Methods: Consecutive children, who underwent radiographic examinations after injury, over 2 years (2019-2021) and with > 2 weeks of follow-up to confirm the presence or absence of a fracture, were included. Four readers, blinded to history and diagnosis, retrospectively reviewed all images twice, without and with cue, at least 1 week apart and after randomization, to determine the presence or absence of a fracture, and if present, anatomic location and diagnostic confidence were recorded.

A longitudinal resource for studying connectome development and its psychiatric associations during childhood.

Most psychiatric disorders are chronic, associated with high levels of disability and distress, and present during pediatric development. Scientific innovation increasingly allows researchers to probe brain-behavior relationships in the developing human. As a result, ambitions to (1) establish normative pediatric brain development trajectories akin to growth curves, (2) characterize reliable metrics for distinguishing illness, and (3) develop clinically useful tools to assist in the diagnosis and management of mental health and learning disorders have gained significant momentum.

Answer ALS, a large-scale resource for sporadic and familial ALS combining clinical and multi-omics data from induced pluripotent cell lines.

Answer ALS is a biological and clinical resource of patient-derived, induced pluripotent stem (iPS) cell lines, multi-omic data derived from iPS neurons and longitudinal clinical and smartphone data from over 1,000 patients with ALS. This resource provides population-level biological and clinical data that may be employed to identify clinical-molecular-biochemical subtypes of amyotrophic lateral sclerosis (ALS). A unique smartphone-based system was employed to collect deep clinical data, including fine motor activity, speech, breathing and linguistics/cognition.

An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients.

Neurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could address these challenges. We investigated DNA, RNA, epigenetics, and proteins in iPSC-derived motor neurons from patients with ALS carrying hexanucleotide expansions in .