Changes in the Incidence and Human Papillomavirus-Positive Portion of Oropharyngeal Squamous Cell Carcinoma in Hong Kong.

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in association with other head and neck cancers.

Rescue of dendritic cells from glycolysis inhibition improves cancer immunotherapy in mice.

Inhibition of glycolysis in immune cells and cancer cells diminishes their activity, and thus combining immunotherapies with glycolytic inhibitors is challenging. Herein, a strategy is presented where glycolysis is inhibited in cancer cells using PFK15 (inhibitor of PFKFB3, rate-limiting step in glycolysis), while simultaneously glycolysis and function is rescued in DCs by delivery of fructose-1,6-biphosphate (F16BP, one-step downstream of PFKFB3). To demonstrate the feasibility of this strategy, vaccine formulations are generated using calcium-phosphate chemistry, that incorporate F16BP, poly(IC) as adjuvant, and phosphorylated-TRP2 peptide antigen and tested in challenging and established YUMM1.

Prehospital Tranexamic Acid for Severe Trauma.

Background: Whether prehospital administration of tranexamic acid increases the likelihood of survival with a favorable functional outcome among patients with major trauma and suspected trauma-induced coagulopathy who are being treated in advanced trauma systems is uncertain.

Methods: We randomly assigned adults with major trauma who were at risk for trauma-induced coagulopathy to receive tranexamic acid (administered intravenously as a bolus dose of 1 g before hospital admission, followed by a 1-g infusion over a period of 8 hours after arrival at the hospital) or matched placebo. The primary outcome was survival with a favorable functional outcome at 6 months after injury, as assessed with the use of the Glasgow Outcome Scale-Extended (GOS-E).

Spatial transcriptomics reveal topological immune landscapes of Asian head and neck angiosarcoma.

Angiosarcomas are rare malignant tumors of the endothelium, arising commonly from the head and neck region (AS-HN) and recently associated with ultraviolet (UV) exposure and human herpesvirus-7 infection. We examined 81 cases of angiosarcomas, including 47 cases of AS-HN, integrating information from whole genome sequencing, gene expression profiling and spatial transcriptomics (10X Visium). In the AS-HN cohort, we observed recurrent somatic mutations in CSMD3 (18%), LRP1B (18%), MUC16 (18%), POT1 (16%) and TP53 (16%).

Vibrio cholerae biofilms use modular adhesins with glycan-targeting and nonspecific surface binding domains for colonization.

Bacterial biofilms are formed on environmental surfaces and host tissues, and facilitate host colonization and antibiotic resistance by human pathogens. Bacteria often express multiple adhesive proteins (adhesins), but it is often unclear whether adhesins have specialized or redundant roles. Here, we show how the model biofilm-forming organism Vibrio cholerae uses two adhesins with overlapping but distinct functions to achieve robust adhesion to diverse surfaces.

Development of Expert-Level Classification of Seizures and Rhythmic and Periodic Patterns During EEG Interpretation.

Background And Objectives: Seizures (SZs) and other SZ-like patterns of brain activity can harm the brain and contribute to in-hospital death, particularly when prolonged. However, experts qualified to interpret EEG data are scarce. Prior attempts to automate this task have been limited by small or inadequately labeled samples and have not convincingly demonstrated generalizable expert-level performance.

Structural basis for substrate selection by the SARS-CoV-2 replicase.

The SARS-CoV-2 RNA-dependent RNA polymerase coordinates viral RNA synthesis as part of an assembly known as the replication-transcription complex (RTC). Accordingly, the RTC is a target for clinically approved antiviral nucleoside analogues, including remdesivir. Faithful synthesis of viral RNAs by the RTC requires recognition of the correct nucleotide triphosphate (NTP) for incorporation into the nascent RNA.

Interrater Reliability of Expert Electroencephalographers Identifying Seizures and Rhythmic and Periodic Patterns in EEGs.

Background And Objectives: The validity of brain monitoring using electroencephalography (EEG), particularly to guide care in patients with acute or critical illness, requires that experts can reliably identify seizures and other potentially harmful rhythmic and periodic brain activity, collectively referred to as "ictal-interictal-injury continuum" (IIIC). Previous interrater reliability (IRR) studies are limited by small samples and selection bias. This study was conducted to assess the reliability of experts in identifying IIIC.

Pathogenic autoantibodies to IFN-γ act through the impedance of receptor assembly and Fc-mediated response.

Anti-interferon (IFN)-γ autoantibodies (AIGAs) are a pathogenic factor in late-onset immunodeficiency with disseminated mycobacterial and other opportunistic infections. AIGAs block IFN-γ function, but their effects on IFN-γ signaling are unknown. Using a single-cell capture method, we isolated 19 IFN-γ-reactive monoclonal antibodies (mAbs) from patients with AIGAs.

The impact of alcohol pricing policies on public health in Hong Kong, China: A modelling study.

Background: Contrary to most developed economies, Hong Kong has reduced and eliminated taxes on beer and wine over the last 15 years and observed increasing alcohol consumption.

Methods: We applied econometric epidemiological modelling to assess the impact of reverting ad valorem taxation to pre-2008 levels (20% on wine and 40% on beer) on consumption and health outcomes. We used 15 years of industry sales and pricing data (2004-2018) to derive 25 own-price and cross-price elasticity estimates.

Impact of change in iron status over time on clinical outcomes in heart failure according to ejection fraction phenotype.

Aims: The importance of iron deficiency (ID) in heart failure with preserved ejection fraction (HFpEF) is unknown. In HF with reduced ejection fraction (HFrEF), ID is reported as an independent predictor of mortality in HF although not all published studies agree. Different definitions of ID have been assessed, and the natural history of untreated ID not established, which may explain the conflicting results.

Money Talks: Pilot Financial Wellness Programs to Promote Positive Financial Planning Behaviors Among Residents.

Problem: Graduate medical education programs and national organizations are becoming more involved in promoting trainee financial wellness. Current literature reports residents have poor financial knowledge, high debt levels, low concern about their finances, and deficits in financial preparedness, but there has been little published on best practices for implementing financial wellness programs for residents or measuring meaningful outcomes of such programs.

Approach: From June 2017 to 2019, the authors invited 277 internal medicine residents from the Stony Brook University Hospital, Montefiore Medical Center, and Johns Hopkins Bayview Medical Center residency programs to participate in financial wellness programs.

Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes.

Background: Coronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis.

Methods: We performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.

Remarkable Response to Olaparib in a Patient with Combined Hepatocellular-Cholangiocarcinoma Harboring a Biallelic Mutation.

Combined hepatocellular cholangiocarcinoma (cHCC-CC) is a rare subtype of primary liver malignancy characterized by aggressive behavior and poor prognosis. Radial surgical resection is the standard curative treatment. However, effective therapeutic options for recurrent or metastatic cHCC-CC are still lacking, mainly because of an insufficient understanding of the molecular and genomic alterations of cHCC-CC, preventing the discovery of specialized targeting therapy.

MR1-Restricted T Cells with MAIT-like Characteristics Are Functionally Conserved in the Pteropid Bat .

Bats are reservoirs for a large number of viruses which have potential to cause major human disease outbreaks, including the current coronavirus disease 2019 (COVID-19) pandemic. Major efforts are underway to understand bat immune response to viruses, whereas much less is known about their immune responses to bacteria. In this study, MR1-restricted T (MR1T) cells were detected through the use of MR1 tetramers in circulation and tissues of (Pa) bats.

Genotype-Guided Dosing of Warfarin in Chinese Adults: A Multicenter Randomized Clinical Trial.

Background: Warfarin is an effective treatment for thromboembolic disease but has a narrow therapeutic index; optimal anticoagulation dosage can differ tremendously among individuals. We aimed to evaluate whether genotype-guided warfarin dosing is superior to routine clinical dosing for the outcomes of interest in Chinese patients.

Methods: We conducted a multicenter, randomized, single-blind, parallel-controlled trial from September 2014 to April 2017 in 15 hospitals in China.

HDAC11 deficiency disrupts oncogene-induced hematopoiesis in myeloproliferative neoplasms.

Protein acetylation is an important contributor to cancer initiation. Histone deacetylase 6 (HDAC6) controls JAK2 translation and protein stability and has been implicated in JAK2-driven diseases best exemplified by myeloproliferative neoplasms (MPNs). By using novel classes of highly selective HDAC inhibitors and genetically deficient mouse models, we discovered that HDAC11 rather than HDAC6 is necessary for the proliferation and survival of oncogenic JAK2-driven MPN cells and patient samples.

Intracameral injection of a chemically cross-linked hydrogel to study chronic neurodegeneration in glaucoma.

Investigation of neurodegeneration in glaucoma, a leading cause of irreversible blindness worldwide, has been obfuscated by the lack of an efficient model that provides chronic, mild to moderate elevation of intraocular pressure (IOP) with preservation of optical media clarity for long term, in vivo interrogation of the structural and functional integrity of the retinal ganglion cells (RGCs). Here, we designed and formulated an injectable hydrogel based on in situ cross-linking of hyaluronic acid functionalized with vinyl sulfone (HA-VS) and thiol groups (HA-SH). Intracameral injection of HA-VS and HA-SH in C57BL/6J mice exhibited mild to moderate elevation of IOP with daily mean IOP ranged between 14 ± 3 and 24 ± 3 mmHg, which led to progressive, regional loss of RGCs evaluated with in vivo, time-lapse confocal scanning laser ophthalmoscopy; a reduction in fractional anisotropy in the optic nerve and the optic tract projected from the eye with increased IOP in diffusion tensor magnetic resonance imaging; a decrease in positive scotopic threshold response in electroretinography; and a decline in visual acuity measured with an optokinetic virtual reality system.

Heart Failure With Preserved Ejection Fraction in the Young.

Background: Heart failure with preserved ejection fraction (HFpEF), traditionally considered a disease of the elderly, may also affect younger patients. However, little is known about HFpEF in the young.

Methods: We prospectively enrolled 1203 patients with HFpEF (left ventricular ejection fraction ≥50%) from 11 Asian regions.

Postmortem Study of Validation of Low Signal on Fat-Suppressed T1-Weighted Magnetic Resonance Imaging as Marker of Lipid Core in Middle Cerebral Artery Atherosclerosis.

Background And Purpose: High signal on T1-weighted fat-suppressed images in middle cerebral artery plaques on ex vivo magnetic resonance imaging was verified to be intraplaque hemorrhage histologically. However, the underlying plaque component of low signal on T1-weighted fat-suppressed images (LST1) has never been explored. Based on our experience, we hypothesized that LST1 might indicate the presence of lipid core within intracranial plaques.

In Vitro Assessment of Histology Verified Intracranial Atherosclerotic Disease by 1.5T Magnetic Resonance Imaging: Concentric or Eccentric?

Background And Purpose: Clinical trial studies show that plaque eccentricity (symmetry) is among the plaque features that have been associated with more frequent cerebrovascular events. Plaque eccentricity of intracranial atherosclerotic disease is unclear because of lacking of cerebral artery specimens.

Methods: 1.

Fluoxetine Maintains a State of Heightened Responsiveness to Motor Training Early After Stroke in a Mouse Model.

Background And Purpose: Data from both humans and animal models suggest that most recovery from motor impairment after stroke occurs in a sensitive period that lasts only weeks and is mediated, in part, by an increased responsiveness to training. Here, we used a mouse model of focal cortical stroke to test 2 hypotheses. First, we investigated whether responsiveness to training decreases over time after stroke.