Conserved Interferon-γ Signaling Drives Clinical Response to Immune Checkpoint Blockade Therapy in Melanoma.

We analyze the transcriptome of baseline and on-therapy tumor biopsies from 101 patients with advanced melanoma treated with nivolumab (anti-PD-1) alone or combined with ipilimumab (anti-CTLA-4). We find that T cell infiltration and interferon-γ (IFN-γ) signaling signatures correspond most highly with clinical response to therapy, with a reciprocal decrease in cell-cycle and WNT signaling pathways in responding biopsies. We model the interaction in 58 human cell lines, where IFN-γ in vitro exposure leads to a conserved transcriptome response unless cells have IFN-γ receptor alterations.

Point-of-Care Ultrasound to Confirm Umbilical Line Placement: Impact of a Simulation Enhanced Curriculum on Neonatal Intensive Care Unit Provider Competency.

Introduction: Neonatal intensive care unit (NICU) provider point-of-care ultrasound (POCUS) procedural competency for umbilical line placement confirmation has not been defined, and the necessary training to achieve competency has not been previously studied. This study's objective was to test the hypothesis that a simulation-enhanced curriculum will improve NICU providers' POCUS competency to confirm umbilical line placement.

Methods: Neonatal intensive care unit providers without prior ultrasound experience were randomized to a curriculum with or without simulation-based training.

Association of race and ethnicity to incident epilepsy, or epileptogenesis, after subdural hematoma.

Objective: To determine whether race is associated with the development of epilepsy after subdural hematoma (SDH), we identified adult survivors of SDH in a statewide administrative dataset and followed them up for at least 1 year for revisits associated with epilepsy.

Methods: We performed a retrospective cohort study using claims data on all discharges from emergency departments (EDs) and hospitals in California. We identified adults (age ≥18 years) admitted from 2005 to 2011 with first-time traumatic and nontraumatic SDH.

Hemochromatosis risk genotype is not associated with colorectal cancer or age at its diagnosis.

Homozygotes for the higher penetrance hemochromatosis risk allele, c.845G>A (p.Cys282Tyr, or C282Y), have been reported to be at a 2- to 3-fold increased risk for colorectal cancer (CRC).

Impact of Age and Sex on α-Syn (α-Synuclein) Knockdown-Mediated Poststroke Recovery.

Background And Purpose: Increased expression of α-Syn (α-Synuclein) is known to mediate secondary brain damage after stroke. We presently studied if α-Syn knockdown can protect ischemic brain irrespective of sex and age.

Methods: Adult and aged male and female mice were subjected to transient middle cerebral artery occlusion.

Deep Learning for Pediatric Posterior Fossa Tumor Detection and Classification: A Multi-Institutional Study.

Background And Purpose: Posterior fossa tumors are the most common pediatric brain tumors. MR imaging is key to tumor detection, diagnosis, and therapy guidance. We sought to develop an MR imaging-based deep learning model for posterior fossa tumor detection and tumor pathology classification.

Diagnostic Performance of LI-RADS Treatment Response Algorithm for Hepatocellular Carcinoma: Adding Ancillary Features to MRI Compared with Enhancement Patterns at CT and MRI.

Background The Liver Imaging Reporting and Data System Treatment Response (LR-TR) algorithm is used to assess the response of hepatocellular carcinoma (HCC) to local-regional therapy (LRT) based on enhancement patterns. The potential value of adding MRI ancillary features (AFs) needs to be investigated. Purpose To evaluate the potential application of MRI AFs in category adjustment to detect pathologic tumor viability in comparison with the LR-TR algorithm in CT and gadoxetic acid-enhanced MRI.

Serum albumin and beta-amyloid deposition in the human brain.

Objectives: To investigate the relationships of serum albumin with in vivo Alzheimer disease (AD) pathologies, including cerebral β-amyloid (Aβ) protein deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMH), in the human brain.

Methods: A total of 396 older adults without dementia underwent comprehensive clinical assessments, measurement of serum albumin level, and multimodal brain imaging, including [C] Pittsburgh compound B-PET, F-fluorodeoxyglucose-PET, and MRI. Serum albumin was categorized as follows: <4.

Evaluation of molecular subtypes and clonal selection during establishment of patient-derived tumor xenografts from gastric adenocarcinoma.

Patient-derived xenografts (PDX) have emerged as an important translational research tool for understanding tumor biology and enabling drug efficacy testing. They are established by transfer of patient tumor into immune compromised mice with the intent of using them as Avatars; operating under the assumption that they closely resemble patient tumors. In this study, we established 27 PDX from 100 resected gastric cancers and studied their fidelity in histological and molecular subtypes.

The Effectiveness of a New Dispatcher-Assisted Basic Life Support Training Program on Quality in Cardiopulmonary Resuscitation Performance During Training and Willingness to Perform Bystander Cardiopulmonary Resuscitation: A Cluster Randomized Controlled Study.

Introduction: A new dispatcher-assisted basic life support training program, called "Home Education and Resuscitation Outcome Study (HEROS)" was developed with a goal to provide high-quality dispatcher-assisted cardiopulmonary resuscitation (CPR) training, with a focus on untrained home bystanders. This study aimed to determine whether the HEROS program is associated with improved quality in CPR performance during training and willingness to provide bystander CPR compared with other basic life support programs without dispatcher-assisted CPR (non-HEROS).

Methods: This clustered randomized trial was conducted in 3 district health centers in Seoul.

Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria.

Background: Up-regulation of hepatic delta-aminolevulinic acid synthase 1 (ALAS1), with resultant accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen, is central to the pathogenesis of acute attacks and chronic symptoms in acute hepatic porphyria. Givosiran, an RNA interference therapy, inhibits ALAS1 expression.

Methods: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned symptomatic patients with acute hepatic porphyria to receive either subcutaneous givosiran (2.

Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group.

Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics.

Phase 1 study of CWP232291 in patients with relapsed or refractory acute myeloid leukemia and myelodysplastic syndrome.

CWP232291 (CWP291) is a small-molecule inhibitor of Wnt signaling that causes degradation of β-catenin via apoptosis induction through endoplasmic reticulum stress activation. This first-in-human, open-label, dose-escalation study to evaluate the safety, maximum tolerated dose (MTD), and preliminary efficacy of CWP291 enrolled 69 patients with hematologic malignancies (acute myeloid leukemia [AML], n = 64; myelodysplastic syndrome, n = 5) in 15 dose-escalation cohorts of 4 to 334 mg/m2 using a modified 3+3 design and 1 dose-expansion cohort. CWP291 was administered IV daily for 7 days every 21 days.

Variability of the Positive Predictive Value of PI-RADS for Prostate MRI across 26 Centers: Experience of the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel.

Background Prostate MRI is used widely in clinical care for guiding tissue sampling, active surveillance, and staging. The Prostate Imaging Reporting and Data System (PI-RADS) helps provide a standardized probabilistic approach for identifying clinically significant prostate cancer. Despite widespread use, the variability in performance of prostate MRI across practices remains unknown.

Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours.

Background: In this first-in-human, Phase 1 study of a microRNA-based cancer therapy, the recommended Phase 2 dose (RP2D) of MRX34, a liposomal mimic of microRNA-34a (miR-34a), was determined and evaluated in patients with advanced solid tumours.

Methods: Adults with various solid tumours refractory to standard treatments were enrolled in 3 + 3 dose-escalation cohorts and, following RP2D determination, expansion cohorts. MRX34, with oral dexamethasone premedication, was given intravenously daily for 5 days in 3-week cycles.

Evaluation and management of blunt cerebrovascular injury: A practice management guideline from the Eastern Association for the Surgery of Trauma.

Background: Blunt cerebrovascular injuries (BCVIs) are associated with significant morbidity and mortality. This guideline evaluates several aspects of BCVI diagnosis and management including the role of screening protocols, criteria for screening cervical spine injuries, and the use of antithrombotic therapy (ATT) and endovascular stents.

Methods: Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, a taskforce of the Practice Management Guidelines Committee of the Eastern Association for the Surgery of Trauma performed a systematic review and meta-analysis of currently available evidence.

Passive immunization with an extended half-life monoclonal antibody protects Rhesus macaques against aerosolized ricin toxin.

Inhalation of ricin toxin (RT), a Category B biothreat agent, provokes an acute respiratory distress syndrome marked by pro-inflammatory cytokine and chemokine production, neutrophilic exudate, and pulmonary edema. The severity of RT exposure is attributed to the tropism of the toxin's B subunit (RTB) for alveolar macrophages and airway epithelial cells, coupled with the extraordinarily potent ribosome-inactivating properties of the toxin's enzymatic subunit (RTA). While there are currently no vaccines or treatments approved to prevent RT intoxication, we recently described a humanized anti-RTA IgG MAb, huPB10, that was able to rescue non-human primates (NHPs) from lethal dose RT aerosol challenge if administered by intravenous (IV) infusion within hours of toxin exposure.

Melbourne Mobile Stroke Unit and Reperfusion Therapy: Greater Clinical Impact of Thrombectomy Than Thrombolysis.

Background and Purpose- Mobile stroke units (MSUs) are increasingly used worldwide to provide prehospital triage and treatment. The benefits of MSUs in giving earlier thrombolysis have been well established, but the impacts of MSUs on endovascular thrombectomy (EVT) and effect on disability avoidance are largely unknown. We aimed to determine the clinical impact and disability reduction for reperfusion therapies in the first operational year of the Melbourne MSU.

Multiphase MR Angiography Collateral Map: Functional Outcome after Acute Anterior Circulation Ischemic Stroke.

Background Collateral circulation determines tissue fate and affects treatment result in acute ischemic stroke. A precise method for collateral estimation in an optimal imaging protocol is necessary to make an appropriate treatment decision for acute ischemic stroke. Purpose To verify the value of multiphase collateral imaging data sets (MR angiography collateral map) derived from dynamic contrast material-enhanced MR angiography for predicting functional outcomes after acute ischemic stroke.

Polymer-based or Polymer-free Stents in Patients at High Bleeding Risk.

Background: Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited.

Methods: In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus-coated stents in patients at high bleeding risk.

Proteomic Atomics Reveals a Distinctive Uracil-5-Methyltransferase.

Carbon (C), hydrogen (H), nitrogen (N), oxygen (O), and sulfur (S) atoms intrigue as they are the foundation for amino acid (AA) composition and the folding and functions of proteins and thus define and control the survival of a cell, the smallest unit of life. Here, we calculated the proteomic atom distribution in >1500 randomly selected species across the entire current phylogenetic tree and identified uracil-5-methyltransferase (U5MTase) of the protozoan parasite Plasmodium falciparum (Pf, strain Pf3D7), with a distinct atom and AA distribution pattern. We determined its apicoplast location and in silico 3D protein structure to refocus attention exclusively on U5MTase with tremendous potential for therapeutic intervention in malaria.

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer.

Background: Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. In a phase 1 dose-finding study, a majority of the patients with advanced HER2-positive breast cancer had a response to trastuzumab deruxtecan (median response duration, 20.7 months).

Kinematic on Ankle and Knee Joint of Post-Stroke Elderly Patients by Wearing Newly Elastic Band-Type Ankle-Foot Orthosis in Gait.

Purpose: The post-stroke elderly was increased caused by increasing stroke and advanced medical. However, ankle-foot orthoses (AFOs) can be uncomfortable for hemiplegic patients; therefore, the usability is not good. In this study, we analyzed ankle and knee joint angles in post-stroke elderly patients to assess the functional effectiveness (specifically prevention of back knee and drop-foot) of a new elastic band-type AFO (New Product: NP) during gait.