Cryptosporidium PI(4)K inhibitor EDI048 is a gut-restricted parasiticidal agent to treat paediatric enteric cryptosporidiosis.

Diarrhoeal disease caused by Cryptosporidium is a major cause of morbidity and mortality in young and malnourished children from low- and middle-income countries, with no vaccine or effective treatment. Here we describe the discovery of EDI048, a Cryptosporidium PI(4)K inhibitor, designed to be active at the infection site in the gastrointestinal tract and undergo rapid metabolism in the liver. By using mutational analysis and crystal structure, we show that EDI048 binds to highly conserved amino acid residues in the ATP-binding site.

Improving prognostic accuracy in lung transplantation using unique features of isolated human lung radiographs.

Ex vivo lung perfusion (EVLP) enables advanced assessment of human lungs for transplant suitability. We developed a convolutional neural network (CNN)-based approach to analyze the largest cohort of isolated lung radiographs to date. CNNs were trained to process 1300 longitudinal radiographs from n = 650 clinical EVLP cases.

Trauma care and its financing around the world.

Abstract: Worldwide, one billion people sustain trauma, and 5 million people will die every year from their injuries. Countries must build trauma systems to effectively address this high-burden disease, but efforts are often challenged by financial constraints. Understanding mechanisms for trauma funding internationally can help to identify opportunities to address the burden of injuries.

A phase II study of cabozantinib and pembrolizumab in advanced gastric/gastroesophageal adenocarcinomas resistant or refractory to immune checkpoint inhibitors.

Background: Most patients with metastatic gastroesophageal adenocarcinoma (mGEA) progress on immune checkpoint inhibitors (ICIs). Novel approaches to overcome resistance to ICI in mGEA are needed. Cabozantinib is a multi-tyrosine kinase inhibitor thought to enhance the immunomodulatory effects of ICI.

The Genetic Variants of Long Noncoding RNA and Its Association to the Clinical Features of Diabetic Retinopathy.

Purpose: This study aimed to investigate the potential correlation between the single-nucleotide polymorphism (SNP) of and the clinical manifestations of diabetic retinopathy (DR).

Methods: Five loci of SNPs including rs4081134 (G/A), rs10144253 (T/C), rs7158663 (G/A), rs3087918 (T/G) and rs11160608 (A/C) were genotyped by TaqMan allelic discrimination in 457 non-DR patients and 280 DR individuals.

Results: The distribution frequency of SNP rs7158663 GA (AOR: 0.

The dilemma of radiation necrosis from diagnosis to treatment in the management of brain metastases.

Radiation therapy with stereotactic radiosurgery (SRS) or whole brain radiation therapy is a mainstay of treatment for patients with brain metastases. The use of SRS in the management of brain metastases is becoming increasingly common and provides excellent local control. Cerebral radiation necrosis (RN) is a late complication of radiation treatment that can be seen months to years following treatment and is often indistinguishable from tumor progression on conventional imaging.

Myeloid-restricted CD68 deficiency attenuates atherosclerosis via inhibition of ROS-MAPK-apoptosis axis.

In atherosclerosis, macrophages derived from blood monocytes contribute to non-resolving inflammation, which subsequently primes necrotic core formation, and ultimately triggers acute thrombotic vascular disease. Nevertheless, little is known about how inflammatory cells, especially the macrophages fuel atherosclerosis. CD68, a unique class D scavenger receptor (SRD) family member, is specifically expressed in monocytes/macrophages and remarkably up-regulated upon oxidized low-density lipoprotein (ox-LDL) stimulation.

Polygenic risk score penetrance & recurrence risk in familial Alzheimer disease.

Objective: To compute penetrance and recurrence risk using a genome-wide PRS (including and excluding the APOE region) in families with Alzheimer's disease.

Methods: Genotypes from the National Institute on Aging Late-Onset Alzheimer's Disease Family-Based Study and a study of familial Alzheimer's disease in Caribbean Hispanics were used to compute PRS with and without variants in the 2 MB region flanking APOE. PRS was calculated in using clumping/thresholding and Bayesian methods and was assessed for association with Alzheimer's disease and age at onset.

Association Between rs2200733 Polymorphism of PITX2 Gene and the Risk of Atrial Fibrillation.

Background: As observed in recent genetic studies, PITX2 is one of the most popular genes with atrial fibrillation; single nucleotide polymorphism (rs2200733) at chromosome 4q25 (near PITX2) is found to be strongly associated with atrial fibrillation, but it has a difference among Chinese Han population. The basic aim of conducting this study is to find the correlation between PITX2 gene polymorphism and the risk of atrial fibrillation and to identify the possibility for early diagnosis of silent atrial fibrillation and high-risk atrial fibrillation.

Methods: The study included 98 cases of atrial fibrillation patients and 88 non-atrial fibrillation patients in Affiliated Hospital of Yangzhou University were enrolled in a case-control study.

Novel Haplotype in the Gene Promoter Associated with Body Length in Pigs.

The screening of important candidate genes and the identification of genetic markers are important for molecular selection in the pig industry. The hematopoietically expressed homeobox () gene plays an important role in embryonic development and organogenesis; however, the genetic variation and expression pattern of the porcine gene remains to be clarified. In this study, semiquantitative RT-PCR and immunohistochemistry results showed the specific expression of the gene in porcine cartilage tissues.

Abnormal Conduction Zone Detected by Isochronal Late Activation Mapping Accurately Identifies the Potential Atrial Substrate and Predicts the Atrial Fibrillation Ablation Outcome After Pulmonary Vein Isolation.

Background: The presence of abnormal substrate of left atrium is a predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation. We aimed to investigate the isochronal late activation mapping to access the abnormal conduction velocity for predicting AF ablation outcome.

Methods: Forty-five paroxysmal AF patients (30 males, 57.

Longitudinal analysis of users transitioning from the Dexcom G5 to the G6 RT-CGM system in Germany, Sweden and the United Kingdom (2018-2020).

Aims: Regional variations in the adoption of diabetes technology may be reflected in population-level metrics of glycaemic control. In this observational study, we aimed to assess the glycaemic impacts of transitioning from the Dexcom G5 Real-Time Continuous Glucose Monitoring (RT-CGM) System to the Dexcom G6 in three European countries.

Methods: Anonymised RT-CGM data (uploaded to the Dexcom Clarity app) were from users in Germany, Sweden, and the United Kingdom (UK) who transitioned from G5 to G6 between 9-12 months after G6 launched in 2018.

Decoding RNA Editing Sites Through Transcriptome Analysis in Rice Under Alkaline Stress.

Ribonucleic acid editing (RE) is a post-transcriptional process that altered the genetics of RNA which provide the extra level of gene expression through insertion, deletions, and substitutions. In animals, it converts nucleotide residues C-U. Similarly in plants, the role of RNA editing sites (RES) in rice under alkaline stress is not fully studied.

VHL mosaicism: the added value of multi-tissue analysis.

Von Hippel-Lindau disease (VHL) is an autosomal dominant, inherited syndrome with variants in the VHL gene causing predisposition to multi-organ benign and malignant neoplasms. A germline VHL variant is identified in 95-100% of individuals with a clinical diagnosis of VHL. Here, we present the case of an individual with a clinical diagnosis of VHL disease where peripheral blood DNA analysis did not detect a VHL variant.

Studies on transmittance modulation and ions transfer kinetic based on capacitive-controlled 2D VOinverse opal film for electrochromic energy storage application.

Two-dimensional vanadium pentoxide inverse opal (2D VOIO) architecture was fabricated by polystyrene (PS) sphere template assisted electrodeposition process. In comparison to the un-templated VOfilm, the 2D VOIO film exhibited a highly ordered hexagonal close-packed bowel-like array, as well as noticeable electrochromism, such as transmittance modulation up to 42.6% at 800 nm, high coloration efficiency (28.

-related Neurodevelopmental Disorder With Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Mimics Pelizaeus-Merzbacher Disease.

Objective: To demonstrate that de novo missense single nucleotide variants (SNVs) in cause a neurodevelopmental disorder with leukoencephalopathy resembling Pelizaeus-Merzbacher disease (PMD).

Methods: A retrospective chart review was performed of 2 unrelated males evaluated at a single institution with de novo SNVs identified by clinical exome sequencing (ES). Clinical and radiographic data were reviewed and summarized.

BPRDP056, a novel small molecule drug conjugate specifically targeting phosphatidylserine for cancer therapy.

Zinc(II)-dipicolylamine (Zn-DPA) has been shown to specifically identify and bind to phosphatidylserine (PS), which exists in bulk in the tumor microenvironment. BPRDP056, a Zn-DPA-SN38 conjugate was designed to provide PS-targeted drug delivery of a cytotoxic SN38 to the tumor microenvironment, thereby allowing a lower dosage of SN38 that induces apoptosis in cancer cells. Micro-Western assay showed that BPRDP056 exhibited apoptotic signal levels similar to those of CPT-11 in the treated tumors growing in mice.

The Clinical Application of the Deep Learning Technique for Predicting Trigger Origins in Patients With Paroxysmal Atrial Fibrillation With Catheter Ablation.

Background: Non-pulmonary vein (NPV) trigger has been reported as an important predictor of recurrence post-atrial fibrillation ablation. Elimination of NPV triggers can reduce the recurrence of postablation atrial fibrillation. Deep learning was applied to preablation pulmonary vein computed tomography geometric slices to create a prediction model for NPV triggers in patients with paroxysmal atrial fibrillation.

Pharmacotherapeutic strategies for treating cocaine use disorder-what do we have to offer?

Background: Cocaine use contines to be a significant public health problem world-wide. However, despite substantial research efforts, no pharmacotherapies are approved for the treatment of cocaine use disorder (CUD).

Argument: Studies have identified positive signals for a range of medications for treating CUD.