No association between cortical dopamine D2 receptor availability and cognition in antipsychotic-naive first-episode psychosis.

Cognitive impairment is an important predictor of disability in schizophrenia. Dopamine neurotransmission in cortical brain regions has been suggested to be of importance for higher-order cognitive processes. The aim of this study was to examine the relationship between extrastriatal dopamine D2-R availability and cognitive function, using positron emission tomography and the high-affinity D2-R radioligand [C]FLB 457, in an antipsychotic-naive sample of 18 first-episode psychosis patients and 16 control subjects.

The patient's voice matters: The impact of advance directives on elderly trauma patients.

Background: Geriatric trauma rates are increasing, yet trauma centers often struggle to provide autonomy regarding decision making to these patients. Advance care planning can assist with this process. Currently, there are limited data on the impact of advance directives (ADs) in elderly trauma patients.

Compositions of sequestrated soil carbon in constructed wetlands of Taiwan.

Constructed wetlands are an ecological engineering technology that has been widely applied to treat anthropogenic wastewater. Until now, few studies have focused on soil carbon (C) in the constructed treatment wetlands in tropical regions. Therefore, this study provides insight into the changes in soil C composition of tropically constructed wetlands at different ages.

Multicenter Validation of a Deep Learning Detection Algorithm for Focal Cortical Dysplasia.

Background And Objective: To test the hypothesis that a multicenter-validated computer deep learning algorithm detects MRI-negative focal cortical dysplasia (FCD).

Methods: We used clinically acquired 3-dimensional (3D) T1-weighted and 3D fluid-attenuated inversion recovery MRI of 148 patients (median age 23 years [range 2-55 years]; 47% female) with histologically verified FCD at 9 centers to train a deep convolutional neural network (CNN) classifier. Images were initially deemed MRI-negative in 51% of patients, in whom intracranial EEG determined the focus.

Allosteric Inhibition of the Tumor-Promoting Interaction Between Exon 2-Depleted Splice Variant of Aminoacyl-Transfer RNA Synthetase-Interacting Multifunctional Protein 2 and Heat Shock Protein 70.

Although protein-protein interactions (PPIs) have emerged as an attractive therapeutic target space, the identification of chemicals that effectively inhibit PPIs remains challenging. Here, we identified through library screening a chemical probe (compound ) that can inhibit the tumor-promoting interaction between the oncogenic factor exon 2-depleted splice variant of aminoacyl-transfer RNA synthetase-interacting multifunctional protein 2 (AIMP2-DX2) and heat shock protein 70 (HSP70). We found that compound binds to the N-terminal subdomain of glutathione -transferase (GST-N) of AIMP2-DX2, causing a direct steric clash with HSP70 and an intramolecular interaction between the N-terminal flexible region and the GST-N of AIMP2-DX2, which induces masking of the HSP70 binding region during molecular dynamics and mutation studies.

Cytosolic delivery of CDK4/6 inhibitor p16 protein using engineered protein crystals for cancer therapy.

The tumor suppressor p16 protein is an endogenous CDK4/6 inhibitor. Inactivation of its encoding gene is found in nearly half of human cancers. Restoration of p16 function via adenovirus-based gene delivery has been shown to be effective in suppressing aberrant cell growth in many types of cancer, however, the potential risk of insertional mutagenesis in genomic DNA remains a major concern.

MRI-Based Machine Learning Prediction Framework to Lateralize Hippocampal Sclerosis in Patients With Temporal Lobe Epilepsy.

Background And Objectives: MRI fails to reveal hippocampal pathology in 30% to 50% of temporal lobe epilepsy (TLE) surgical candidates. To address this clinical challenge, we developed an automated MRI-based classifier that lateralizes the side of covert hippocampal pathology in TLE.

Methods: We trained a surface-based linear discriminant classifier that uses T1-weighted (morphology) and T2-weighted and fluid-attenuated inversion recovery (FLAIR)/T1 (intensity) features.

Deep Learning for Detection of Pulmonary Metastasis on Chest Radiographs.

Background A computer-aided detection (CAD) system may help surveillance for pulmonary metastasis at chest radiography in situations where there is limited access to CT. Purpose To evaluate whether a deep learning (DL)-based CAD system can improve diagnostic yield for newly visible lung metastasis on chest radiographs in patients with cancer. Materials and Methods A regulatory-approved CAD system for lung nodules was implemented to interpret chest radiographs from patients referred by the medical oncology department in clinical practice.

Deep Learning for Automated Diabetic Retinopathy Screening Fused With Heterogeneous Data From EHRs Can Lead to Earlier Referral Decisions.

Purpose: Fundus images are typically used as the sole training input for automated diabetic retinopathy (DR) classification. In this study, we considered several well-known DR risk factors and attempted to improve the accuracy of DR screening.

Metphods: Fusing nonimage data (e.

NAD Redox Imbalance in the Heart Exacerbates Diabetic Cardiomyopathy.

Background: Diabetes is a risk factor for heart failure and promotes cardiac dysfunction. Diabetic tissues are associated with nicotinamide adenine dinucleotide (NAD) redox imbalance; however, the hypothesis that NAD redox imbalance causes diabetic cardiomyopathy has not been tested. This investigation used mouse models with altered NAD redox balance to test this hypothesis.

Rare Coding Variants Associated With Electrocardiographic Intervals Identify Monogenic Arrhythmia Susceptibility Genes: A Multi-Ancestry Analysis.

Background: Alterations in electrocardiographic (ECG) intervals are well-known markers for arrhythmia and sudden cardiac death (SCD) risk. While the genetics of arrhythmia syndromes have been studied, relations between electrocardiographic intervals and rare genetic variation at a population level are poorly understood.

Methods: Using a discovery sample of 29 000 individuals with whole-genome sequencing from Trans-Omics in Precision Medicine and replication in nearly 100 000 with whole-exome sequencing from the UK Biobank and MyCode, we examined associations between low-frequency and rare coding variants with 5 routinely measured electrocardiographic traits (RR, P-wave, PR, and QRS intervals and corrected QT interval).

An Exploration of Blood Marker×Environment Interaction Effects on Pain Severity and Interference Scores in People With Acute Musculoskeletal Trauma.

Objectives: Explore the moderating effects of psychological or social variables on associations between biomarkers of inflammation/stress and clinical reports of pain.

Methods: This is a cross-sectional exploratory study. Data were drawn from the Systematic Merging of Biology, Mental Health and Environment (SYMBIOME) longitudinal study (clinicaltrials.

Trends in Occupational Radiation Doses for U.S. Radiologic Technologists Performing General Radiologic and Nuclear Medicine Procedures, 1980-2015.

Background Occupational doses to most medical radiation workers have declined substantially since the 1950s because of improvements in radiation protection practices. However, different patterns may have emerged for radiologic technologists working with nuclear medicine because of the higher per-procedure doses and increasing workloads. Purpose To summarize annual occupational doses during a 36-year period for a large cohort of U.

Clinical Characteristics and Predictors of In-Hospital Mortality in Patients With Cardiogenic Shock: Results From the RESCUE Registry.

Background: In the current era of mechanical circulatory support, limited data are available on prognosis of cardiogenic shock (CS) caused by various diseases. We investigated the characteristics and predictors of in-hospital mortality in Korean patients with CS.

Methods: The RESCUE study (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With CS) is a multicenter, retrospective, and prospective registry of patients that presented with CS.

Antibody-drug conjugates with dual payloads for combating breast tumor heterogeneity and drug resistance.

Breast tumors generally consist of a diverse population of cells with varying gene expression profiles. Breast tumor heterogeneity is a major factor contributing to drug resistance, recurrence, and metastasis after chemotherapy. Antibody-drug conjugates (ADCs) are emerging chemotherapeutic agents with striking clinical success, including T-DM1 for HER2-positive breast cancer.

Association of Aberrant Posterior Vitreous Detachment and Pathologic Tractional Forces With Myopic Macular Degeneration.

Purpose: The purpose of this study was to assess whether the tractional elements of pathologic myopia (PM; e.g. myopic traction maculopathy [MTM], posterior staphyloma [PS], and aberrant posterior vitreous detachment [PVD]) are associated with myopic macular degeneration (MMD) independent of age and axial length, among highly myopic (HM) eyes.

Extrafollicular IgD+ B cells generate IgE antibody secreting cells in the nasal mucosa.

Increased IgE is a typical feature of allergic rhinitis. Local class-switch recombination has been intimated but B cell precursors and mechanisms remain elusive. Here we describe the dynamics underlying the generation of IgE-antibody secreting cells (ASC) in human nasal polyps (NP), mucosal tissues rich in ASC without germinal centers (GC).

Impact of Socioeconomic Status, Race and Ethnicity, and Geography on Prenatal Detection of Hypoplastic Left Heart Syndrome and Transposition of the Great Arteries.

Background: Prenatal detection (PND) has benefits for infants with hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA), but associations between sociodemographic and geographic factors with PND have not been sufficiently explored. This study evaluated whether socioeconomic quartile (SEQ), public insurance, race and ethnicity, rural residence, and distance of residence (distance and driving time from a cardiac surgical center) are associated with the PND or timing of PND, with a secondary aim to analyze differences between the United States and Canada.

Methods: In this retrospective cohort study, fetuses and infants <2 months of age with HLHS or TGA admitted between 2012 and 2016 to participating Fetal Heart Society Research Collaborative institutions in the United States and Canada were included.

Pathological drivers of neurodegeneration in suspected non-Alzheimer's disease pathophysiology.

Background: Little is known about the heterogeneous etiology of suspected non-Alzheimer's pathophysiology (SNAP), a group of subjects with neurodegeneration in the absence of β-amyloid. Using antemortem MRI and pathological data, we investigated the etiology of SNAP and the association of neurodegenerative pathologies with structural medial temporal lobe (MTL) measures in β-amyloid-negative subjects.

Methods: Subjects with antemortem MRI and autopsy data were selected from ADNI (n=63) and the University of Pennsylvania (n=156).

Engineered red blood cells as an off-the-shelf allogeneic anti-tumor therapeutic.

Checkpoint inhibitors and T-cell therapies have highlighted the critical role of T cells in anti-cancer immunity. However, limitations associated with these treatments drive the need for alternative approaches. Here, we engineer red blood cells into artificial antigen-presenting cells (aAPCs) presenting a peptide bound to the major histocompatibility complex I, the costimulatory ligand 4-1BBL, and interleukin (IL)-12.

Ischemic Stroke, Inflammation, and Endotheliopathy in COVID-19 Patients.

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Long Noncoding RNA Fos Downstream Transcript Is Developmentally Dispensable but Vital for Shaping the Poststroke Functional Outcome.

Background And Purpose: Stroke induces the expression of several long noncoding RNAs in the brain. However, their functional significance in poststroke outcome is poorly understood. We recently observed that a brain-specific long noncoding RNA called Fos downstream transcript (FosDT) is induced rapidly in the rodent brain following focal ischemia.