FAIR enough: Building an academic data ecosystem to make real-world data available for translational research.

The Stanford Population Health Sciences Data Ecosystem was created to facilitate the use of large datasets containing health records from hundreds of millions of individuals. This necessitated technical solutions optimized for an academic medical center to manage and share high-risk data at scale. Through collaboration with internal and external partners, we have built a Data Ecosystem to host, curate, and share data with hundreds of users in a secure and compliant manner.

Endovascular coiling versus neurosurgical clipping in the management of aneurysmal subarachnoid haemorrhage in the elderly: a multicenter cohort study.

The comparability of endovascular coiling over neurosurgical clipping has not been firmly established in elderly patients with aneurysmal subarachnoid haemorrhage (aSAH). Data were obtained from all patients with aSAH aged ≥60 across three tertiary hospitals in Singapore from 2014 to 2019. Outcome measures included modified Rankin Scale (mRS) score at 3 and at 6 months, and in-hospital mortality.

Metabolic programs of T cell tissue residency empower tumour immunity.

Tissue resident memory CD8 T (T) cells offer rapid and long-term protection at sites of reinfection. Tumour-infiltrating lymphocytes with characteristics of T cells maintain enhanced effector functions, predict responses to immunotherapy and accompany better prognoses. Thus, an improved understanding of the metabolic strategies that enable tissue residency by T cells could inform new approaches to empower immune responses in tissues and solid tumours.

ReIGNITE Radiation Therapy Boost: A Prospective, International Study of Radiation Oncologists' Accuracy in Contouring Prostate Tumors for Focal Radiation Therapy Boost on Conventional Magnetic Resonance Imaging Alone or With Assistance of Restriction Spectrum Imaging.

Purpose: In a phase III randomized trial, adding a radiation boost to tumor(s) visible on MRI improved prostate cancer (PCa) disease-free and metastasis-free survival without additional toxicity. Radiation oncologists' ability to identify prostate tumors is critical to widely adopting intraprostatic tumor radiotherapy boost for patients. A diffusion MRI biomarker, called the Restriction Spectrum Imaging restriction score (RSIrs), has been shown to improve radiologists' identification of clinically significant PCa.

Factors reducing inappropriate attendances to emergency departments before and during the COVID-19 pandemic: A multicentre study.

Introduction: Inappropriate attendances (IAs) to emergency departments (ED) create an unnecessary strain on healthcare systems. With decreased ED attendance during the COVID-19 pandemic, this study postulates that there are less IAs compared to before the pandemic and identifies factors associated with IAs.

Methods: We performed a retrospective review of 29,267 patient presentations to a healthcare cluster in Singapore from 7 April 2020 to 1 June 2020, and 36,370 patients within a corresponding period in 2019.

Nontargeted mass spectrometry of dried blood spots for interrogation of the human circulating metabolome.

Advances in high-resolution, nontargeted mass spectrometry allow for the simultaneous measure of thousands of metabolites in a single biosample. Application of these analytical approaches to population-scale human studies has been limited by the need for resource-intensive blood sample collection, preparation, and storage. Dried blood spotting, a technique developed decades ago for newborn screening, may offer a simple approach to overcome barriers in human blood acquisition and storage.

Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease.

Background: Recent studies highlight the role of metabolites in immune diseases, but it remains unknown how much of this effect is driven by genetic and non-genetic host factors.

Result: We systematically investigate circulating metabolites in a cohort of 500 healthy subjects (500FG) in whom immune function and activity are deeply measured and whose genetics are profiled. Our data reveal that several major metabolic pathways, including the alanine/glutamate pathway and the arachidonic acid pathway, have a strong impact on cytokine production in response to ex vivo stimulation.

Access to Essential Surgical Care in Chiapas, Mexico: A System-Wide Geospatial Analysis.

Background: Long travel times to reach essential surgical care in Chiapas, Mexico's poorest state, can delay lifesaving procedures and contribute to adverse outcomes. Geographical access to surgical facilities is 1 of the 6 indicators of the Lancet Commission on Global Surgery and has been measured extensively worldwide. Our objective is to determine the population with 2-h geographical access to facilities capable of performing the Bellwether procedures (laparotomy, cesarean delivery, and open fracture repair).

Functional Analysis of Immune Signature Genes in Th1* Memory Cells Links ISOC1 and Pyrimidine Metabolism to IFN-γ and IL-17 Production.

CCR6CXCR3CCR4CD4 memory T cells, termed Th1*, are important for long-term immunity to and the pathogenesis of autoimmune diseases. Th1* cells express a unique set of lineage-specific transcription factors characteristic of both Th1 and Th17 cells and display distinct gene expression profiles compared with other CD4 T cell subsets. To examine molecules and signaling pathways important for the effector function of Th1* cells, we performed loss-of-function screening of genes selectively enriched in the Th1* subset.

Close air support: enhancing emergency care in the COVID-19 pandemic.

The COVID-19 pandemic has taken the world by storm and overwhelmed healthcare institutions even in developed countries. In response, clinical staff and resources have been redeployed to the areas of greatest need, that is, intensive care units and emergency rooms (ER), to reinforce front-line manpower. We introduce the concept of close air support (CAS) to augment ER operations in an efficient, safe and scalable manner.

CBASS Immunity Uses CARF-Related Effectors to Sense 3'-5'- and 2'-5'-Linked Cyclic Oligonucleotide Signals and Protect Bacteria from Phage Infection.

cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes are immune sensors that synthesize nucleotide second messengers and initiate antiviral responses in bacterial and animal cells. Here, we discover Enterobacter cloacae CD-NTase-associated protein 4 (Cap4) as a founding member of a diverse family of >2,000 bacterial receptors that respond to CD-NTase signals. Structures of Cap4 reveal a promiscuous DNA endonuclease domain activated through ligand-induced oligomerization.

Predicted annual energy yield of III-V/c-Si tandem solar cells: modelling the effect of changing spectrum on current-matching.

High efficiencies of >30% are predicted for series-connected tandem solar cells when current-matching is achieved between the wide-bandgap top cell and silicon bottom cell. Sub-cells are typically optimized for current-matching based on the standard AM1.5G spectrum, but in practice, the incident radiation on a solar cell can be very different from this standard due to the effects of the sun's location in the sky, atmospheric conditions, total diffuse element etc.

HORMA Domain Proteins and a Trip13-like ATPase Regulate Bacterial cGAS-like Enzymes to Mediate Bacteriophage Immunity.

Bacteria are continually challenged by foreign invaders, including bacteriophages, and have evolved a variety of defenses against these invaders. Here, we describe the structural and biochemical mechanisms of a bacteriophage immunity pathway found in a broad array of bacteria, including E. coli and Pseudomonas aeruginosa.

Structure and Mechanism of a Cyclic Trinucleotide-Activated Bacterial Endonuclease Mediating Bacteriophage Immunity.

Bacteria possess an array of defenses against foreign invaders, including a broadly distributed bacteriophage defense system termed CBASS (cyclic oligonucleotide-based anti-phage signaling system). In CBASS systems, a cGAS/DncV-like nucleotidyltransferase synthesizes cyclic di- or tri-nucleotide second messengers in response to infection, and these molecules activate diverse effectors to mediate bacteriophage immunity via abortive infection. Here, we show that the CBASS effector NucC is related to restriction enzymes but uniquely assembles into a homotrimer.

Geospatial Mapping as a Guide for Resource Allocation Among Burn Centers in India.

Timely treatment is essential for optimal outcomes after burn injury, but the method of resource distribution to ensure access to proper care in developing countries remains unclear. We therefore sought to examine access to burn care and the presence/absence of resources for burn care in India. We surveyed all eligible burn centers (n = 67) in India to evaluate burn care resources at each facility.

Validation of Zip Code-Based Estimates of Ambulance Driving Distance to Control for Access to Care in Emergency Surgery Research.

This study uses Medicaid data files to estimate the association of estimated driving distance and reported driven ambulance miles from an injury site to a hospital during emergency medical service calls as a means to assess data accuracy for use in future research.

Identification of aurintricarboxylic acid as a selective inhibitor of the TWEAK-Fn14 signaling pathway in glioblastoma cells.

The survival of patients diagnosed with glioblastoma (GBM), the most deadly form of brain cancer, is compromised by the proclivity for local invasion into the surrounding normal brain, which prevents complete surgical resection and contributes to therapeutic resistance. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) superfamily, can stimulate glioma cell invasion and survival via binding to fibroblast growth factor-inducible 14 (Fn14) and subsequent activation of the transcription factor NF-κB. To discover small molecule inhibitors that disrupt the TWEAK-Fn14 signaling axis, we utilized a cell-based drug-screening assay using HEK293 cells engineered to express both Fn14 and a NF-κB-driven firefly luciferase reporter protein.

SGEF Is Regulated via TWEAK/Fn14/NF-κB Signaling and Promotes Survival by Modulation of the DNA Repair Response to Temozolomide.

Unlabelled: Glioblastoma (GB) is the highest grade and most common form of primary adult brain tumors. Despite surgical removal followed by concomitant radiation and chemotherapy with the alkylating agent temozolomide, GB tumors develop treatment resistance and ultimately recur. Impaired response to treatment occurs rapidly, conferring a median survival of just fifteen months.

Propentofylline inhibits glioblastoma cell invasion and survival by targeting the TROY signaling pathway.

Glioblastoma (GBM) is the most common primary tumor of the CNS and carries a dismal prognosis. The aggressive invasion of GBM cells into the surrounding normal brain makes complete resection impossible, significantly increases resistance to the standard therapy regimen, and virtually assures tumor recurrence. Median survival for newly diagnosed GBM is 14.

Mcl-1 mediates TWEAK/Fn14-induced non-small cell lung cancer survival and therapeutic response.

Unlabelled: Insensitivity to standard clinical interventions, including chemotherapy, radiotherapy, and tyrosine kinase inhibitor (TKI) treatment, remains a substantial hindrance towards improving the prognosis of patients with non-small cell lung cancer (NSCLC). The molecular mechanism of therapeutic resistance remains poorly understood. The TNF-like weak inducer of apoptosis (TWEAK)-FGF-inducible 14 (TNFRSF12A/Fn14) signaling axis is known to promote cancer cell survival via NF-κB activation and the upregulation of prosurvival Bcl-2 family members.

Implications of Rho GTPase Signaling in Glioma Cell Invasion and Tumor Progression.

Glioblastoma (GB) is the most malignant of primary adult brain tumors, characterized by a highly locally invasive cell population, as well as abundant proliferative cells, neoangiogenesis, and necrosis. Clinical intervention with chemotherapy or radiation may either promote or establish an environment for manifestation of invasive behavior. Understanding the molecular drivers of invasion in the context of glioma progression may be insightful in directing new treatments for patients with GB.

The Src homology 3 domain-containing guanine nucleotide exchange factor is overexpressed in high-grade gliomas and promotes tumor necrosis factor-like weak inducer of apoptosis-fibroblast growth factor-inducible 14-induced cell migration and invasion via tumor necrosis factor receptor-associated factor 2.

Glioblastoma (GB) is the highest grade of primary adult brain tumors, characterized by a poorly defined and highly invasive cell population. Importantly, these invading cells are attributed with having a decreased sensitivity to radiation and chemotherapy. TNF-like weak inducer of apoptosis (TWEAK)-Fn14 ligand-receptor signaling is one mechanism in GB that promotes cell invasiveness and survival and is dependent upon the activity of multiple Rho GTPases, including Rac1.