Lead Optimization of Second-Generation Acridones as Broad-Spectrum Antimalarials.

The global impact of malaria remains staggering despite extensive efforts to eradicate the disease. With increasing drug resistance and the absence of a clinically available vaccine, there is an urgent need for novel, affordable, and safe drugs for prevention and treatment of malaria. Previously, we described a novel antimalarial acridone chemotype that is potent against both blood-stage and liver-stage malaria parasites.

The Enhancement of Leak Detection Performance for Water Pipelines through the Renovation of Training Data.

Leakage detection is a fundamental problem in water management. Its importance is expressed not only in avoiding resource wastage, but also in protecting the environment and the safety of water resources. Therefore, early leak detection is increasingly urged.

A Cluster Randomized Controlled Trial of a Lay Health Worker Intervention to Increase Healthy Eating and Physical Activity Among Vietnamese Americans.

Introduction: Americans have low levels of knowledge of and adherence to recommendations for healthy eating of fruits and vegetables and for physical activity (HEPA). We conducted a cluster randomized controlled trial of a lay health worker intervention to increase HEPA among Vietnamese Americans.

Methods: We randomized 64 lay health workers to 2 intervention arms.

Clinical and radiological features that predict malignant transformation in cystic lesions of the pancreas: a retrospective case note review.

Pancreatic cystic lesions (PCL) are being detected with increasing frequency. Current methods of stratifying risk of malignant transformation are imperfect. This study aimed to determine the frequency of pancreatic malignancy in patients with PCL and define clinical and radiological features that predict malignant transformation in patients managed by surgery and/or surveillance.

Evaluation of circulating transcript analysis (NETest) in small intestinal neuroendocrine neoplasms after surgical resection.

Purpose: Surgical resection is the only effective curative strategy for small intestinal neuroendocrine neoplasms (SINENs). Nevertheless, the evaluation of residual disease and prediction of disease recurrence/progression remains a problematic issue.

Methods: We evaluated 13 SINENs that underwent surgical resection of the primary tumour and/or mesenteric mass.

Locally Informed Simulation to Predict Hospital Capacity Needs During the COVID-19 Pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic challenges hospital leaders to make time-sensitive, critical decisions about clinical operations and resource allocations.

Objective: To estimate the timing of surges in clinical demand and the best- and worst-case scenarios of local COVID-19-induced strain on hospital capacity, and thus inform clinical operations and staffing demands and identify when hospital capacity would be saturated.

Design: Monte Carlo simulation instantiation of a susceptible, infected, removed (SIR) model with a 1-day cycle.

Apparent treatment-resistant hypertension: characteristics and prevalence in a real-world environment of an integrated health system.

Objectives: We compared the prevalence of apparent treatment-resistant hypertension (aTRH) according to the seventh report of the Joint National Committee (JNC 7) and the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline in an integrated healthcare delivery system.

Methods: We identified individuals aged at least 18 years with hypertension from Kaiser Permanente Southern California between 1 July 2014 and 30 June 2015. aTRH was defined as either blood pressure (BP) above goal (≥140/90 mmHg per JNC7, and ≥130/80 mmHg per 2017 ACC/AHA for most adults with hypertension) while taking at least 3 classes of antihypertensive medication or taking at least four classes regardless of BP level.

Circulating uromodulin inhibits vascular calcification by interfering with pro-inflammatory cytokine signalling.

Aims: Uromodulin is produced exclusively in the kidney and secreted into both urine and blood. Serum levels of uromodulin are correlated with kidney function and reduced in chronic kidney disease (CKD) patients, but physiological functions of serum uromodulin are still elusive. This study investigated the role of uromodulin in medial vascular calcification, a key factor associated with cardiovascular events and mortality in CKD patients.

Engineering clinically-relevant human fibroblastic cell-derived extracellular matrices.

Three-dimensional (3D) culturing models, replicating in vivo tissue microenvironments that incorporate native extracellular matrix (ECM), have revolutionized the cell biology field. Fibroblastic cells generate lattices of interstitial ECM proteins. Cell interactions with ECMs and with molecules sequestered/stored within these are crucial for tissue development and homeostasis maintenance.

Acute Hyperketonemia Does Not Affect Glucose or Palmitate Uptake in Abdominal Organs or Skeletal Muscle.

Context: It has recently been hypothesized that ketone bodies may have independent cardioprotective effects due to increased myocardial efficiency and that this may explain the improved survival of individuals with type 2 diabetes treated with mildly ketogenic sodium-glucose cotransporter-2 inhibitors.

Objective: To determine whether ketone bodies are selectively utilized in tissues critical for preservation of conscience and circulation. We investigated the effect of acute hyperketonemia on substrate metabolism in less prioritized tissues such as abdominal organs, adipose tissue, and skeletal muscle.

A Genome-wide ER-phagy Screen Highlights Key Roles of Mitochondrial Metabolism and ER-Resident UFMylation.

Selective autophagy of organelles is critical for cellular differentiation, homeostasis, and organismal health. Autophagy of the ER (ER-phagy) is implicated in human neuropathy but is poorly understood beyond a few autophagosomal receptors and remodelers. By using an ER-phagy reporter and genome-wide CRISPRi screening, we identified 200 high-confidence human ER-phagy factors.

Treatment Course of Patients with Exudative Age-Related Macular Degeneration Using Ocular Hypotensives.

Purpose: To characterize the visual outcomes and the treatment course of patients with exudative age-related macular degeneration (AMD) based on ocular hypotensive use.

Design: A matched retrospective cohort study of patients enrolled in Kaiser Permanente Southern California health plan was conducted. Patients taking ocular hypotensives were identified using pharmacy dispensing data and were matched to controls to compare visual acuity, number of anti-VEGF injections, and conversation to secondary anti-VEGF agents in the first year of treatment.

68Ga-Prostate-Specific Membrane Antigen Uptake in a Pancreatic Neuroendocrine Tumor.

We present a 60-year-old man with known prostate cancer treated with robot-assisted radical prostatectomy. Prostate-specific antigen levels did not decline accordingly, and a second Ga-PSMA PET/CT demonstrated a new focus with high Ga-PSMA uptake in the pancreatic tail. A subsequent CT scan did not display the lesion as a typical pancreatic tumor, and a spleen scintigraphy was also negative excluding an ectopic intrapancreatic accessory spleen.

In Situ functionalization of Poly(hydroxyethyl methacrylate) Cryogels with Oligopeptides via β-Cyclodextrin-Adamantane Complexation for Studying Cell-Instructive Peptide Environment.

Oligopeptides are versatile cell modulators resembling pleiotropic activities of ECM proteins and growth factors. Studying the role of cell-instructive peptide signals within 3D scaffolds, yet poorly known, requires effective approaches to introducing bioactive sequences into appropriate materials. We synthesized RGD and GHK motif based peptides and linked to the terminal adamantyl group (Ad) and their fluorescent derivatives and .

Potential Antidiabetic Activity of Extracts and Isolated Compound from (Bonati).

Bonati. () has been used in traditional and modern medicine in Vietnam for curing hepatitis. In this study, ethanol and aqueous extracts of were evaluated for their α-glucosidase inhibitory activities and anti-hyperglycemic effects on glucose loaded hyperglycemic and streptozotocin (STZ) induced diabetic mice.

Cutaneous pilomatrical carcinosarcoma: a case report with molecular analysis and literature review.

Background: Cutaneous pilomatrical carcinosarcoma (CS) is a very rare biphasic tumor composed of admixed epithelial and mesenchymal malignant cells, with limited information on its pathogenesis. We report a case of pilomatrical CS of the scalp with comparative immunohistochemical and molecular analysis together with a review of the literature.

Case Presentation: A 74-year-old woman presented with a rapidly growing long-standing tumor of the scalp.

Disparities in Stage at Diagnosis in an Equal-access Integrated Delivery System: A Retrospective Cohort Study of 7244 Patients With Bladder Cancer.

Background: Disparities in bladder cancer survival by race/ethnicity and gender are likely related to differences in diagnosis. We assessed disparities in stage at diagnosis and potential contributing factors within a large, integrated delivery system.

Patients And Methods: We conducted a retrospective cohort study of 7244 patients with bladder cancer age ≥ 21 years diagnosed from January 2001 to June 2015 within Kaiser Permanente Southern California.

Cirrhotic Human Liver Extracellular Matrix 3D Scaffolds Promote Smad-Dependent TGF-β1 Epithelial Mesenchymal Transition.

An altered liver microenvironment characterized by a dysregulated extracellular matrix (ECM) supports the development and progression of hepatocellular carcinoma (HCC). The development of experimental platforms able to reproduce these physio-pathological conditions is essential in order to identify and validate new therapeutic targets for HCC. The aim of this work was to validate a new in vitro model based on engineering three-dimensional (3D) healthy and cirrhotic human liver scaffolds with HCC cells recreating the micro-environmental features favoring HCC.

Risk Stratification for Postoperative Acute Kidney Injury in Major Noncardiac Surgery Using Preoperative and Intraoperative Data.

Importance: Acute kidney injury (AKI) is one of the most common complications after noncardiac surgery. Yet current postoperative AKI risk stratification models have substantial limitations, such as limited use of perioperative data.

Objective: To examine whether adding preoperative and intraoperative data is associated with improved prediction of noncardiac postoperative AKI.

Blockade of dengue virus transmission from viremic blood to Aedes aegypti mosquitoes using human monoclonal antibodies.

Background: Dengue is the most prevalent arboviral disease of humans. Virus neutralizing antibodies are likely to be critical for clinical immunity after vaccination or natural infection. A number of human monoclonal antibodies (mAbs) have previously been characterized as able to neutralize the infectivity of dengue virus (DENV) for mammalian cells in cell-culture systems.

Endoscopic ultrasound-guided fine-needle aspiration vs fine-needle biopsy for the diagnosis of pancreatic neuroendocrine tumors.

 Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as a method of obtaining preoperative diagnosis of pancreatic neuroendocrine tumors (PanNETs) has been reported in several series. Fine-needle biopsies (FNB) are increasingly employed to obtain core specimens during EUS. However, the differences in efficacy between these sampling methods in the diagnosis of PanNETs still needs to be defined.

Retrospective study on mixed neuroendocrine non-neuroendocrine neoplasms from five European centres.

Background: Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare diagnosis, mainly encountered in the gastro-entero-pancreatic tract. There is limited knowledge of its epidemiology, prognosis and biology, and the best management for affected patients is still to be defined.

Aim: To investigate clinical-pathological characteristics, treatment modalities and survival outcomes of a retrospective cohort of patients with a diagnosis of MiNEN.

Preoperative factors associated with prolonged postoperative in-hospital length of stay in patients with Crohn's disease undergoing intestinal resection or strictureplasty.

Purpose: To investigate factors that influence postoperative in-hospital length of stay (LOS) in patients with Crohn's disease (CD) undergoing bowel surgery. Furthermore, the study aimed to evaluate LOS as a surrogate for postoperative outcome.

Methods: This is a multicentre retrospective cohort study.

Diagnostic Approaches to Neuroendocrine Neoplasms of Unknown Primary Site.

Neuroendocrine neoplasms (NENs) arise from cells of neuronal and endocrine differentiation. While they are a rare entity, an increasing proportion of patients with NEN present with metastatic disease and no evident primary site using routine imaging or histopathology. NENs of unknown primary site have a poorer prognosis, often due to the challenge of selecting appropriate evidence-based management.

Clinicopathological correlations of mesenteric fibrosis and evaluation of a novel biomarker for fibrosis detection in small bowel neuroendocrine neoplasms.

Purpose: Mesenteric fibrosis (MF) in small intestinal neuroendocrine neoplasms (SINENs) is often associated with significant morbidity and mortality. The detection of MF is usually based on radiological criteria, but no previous studies have attempted a prospective, multidimensional assessment of mesenteric desmoplasia to determine the accuracy of radiological measurements. There is also a lack of non-invasive biomarkers for the detection of image-negative MF.