Rapid and Accurate Diagnosis of Dermatophyte Infections Using the DendrisCHIP Technology.

Dermatophytosis is a superficial fungal infection with an ever-increasing number of patients. Culture-based mycology remains the most commonly used diagnosis, but it takes around four weeks to identify the causative agent. Therefore, routine clinical laboratories need rapid, high throughput, and accurate species-specific analytical methods for diagnosis and therapeutic management.

Familial Recurrence Patterns in Congenitally Corrected Transposition of the Great Arteries: An International Study.

Background: Congenitally corrected transposition of the great arteries (ccTGA) is a rare disease of unknown cause. We aimed to better understand familial recurrence patterns.

Methods: An international, multicentre, retrospective cohort study was conducted in 29 tertiary hospitals in 6 countries between 1990 and 2018, entailing investigation of 1043 unrelated ccTGA probands.

CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition.

Amplification of the CCNE1 locus on chromosome 19q12 is prevalent in multiple tumour types, particularly in high-grade serous ovarian cancer, uterine tumours and gastro-oesophageal cancers, where high cyclin E levels are associated with genome instability, whole-genome doubling and resistance to cytotoxic and targeted therapies. To uncover therapeutic targets for tumours with CCNE1 amplification, we undertook genome-scale CRISPR-Cas9-based synthetic lethality screens in cellular models of CCNE1 amplification. Here we report that increasing CCNE1 dosage engenders a vulnerability to the inhibition of the PKMYT1 kinase, a negative regulator of CDK1.

Geospatial Cellular Distribution of Cancer-Associated Fibroblasts Significantly Impacts Clinical Outcomes in Metastatic Clear Cell Renal Cell Carcinoma.

Cancer-associated fibroblasts (CAF) are highly prevalent cells in the tumor microenvironment in clear cell renal cell carcinoma (ccRCC). CAFs exhibit a pro-tumor effect in vitro and have been implicated in tumor cell proliferation, metastasis, and treatment resistance. Our objective is to analyze the geospatial distribution of CAFs with proliferating and apoptotic tumor cells in the ccRCC tumor microenvironment and determine associations with survival and systemic treatment.

Bacterial cyclic diguanylate signaling networks sense temperature.

Many bacteria use the second messenger cyclic diguanylate (c-di-GMP) to control motility, biofilm production and virulence. Here, we identify a thermosensory diguanylate cyclase (TdcA) that modulates temperature-dependent motility, biofilm development and virulence in the opportunistic pathogen Pseudomonas aeruginosa. TdcA synthesizes c-di-GMP with catalytic rates that increase more than a hundred-fold over a ten-degree Celsius change.

New recessive mutations in causing severe presynaptic congenital myasthenic syndromes.

Objective: To report the identification of 2 new homozygous recessive mutations in the synaptotagmin 2 () gene as the genetic cause of severe and early presynaptic forms of congenital myasthenic syndromes (CMSs).

Methods: Next-generation sequencing identified new homozygous intronic and frameshift mutations in the gene as a likely cause of presynaptic CMS. We describe the clinical and electromyographic patient phenotypes, perform ex vivo splicing analyses to characterize the effect of the intronic mutation on exon splicing, and analyze the functional impact of this variation at the neuromuscular junction (NMJ).

Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis.

An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long-term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB-TURSO or placebo.

Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis.

Background: Sodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. The efficacy and safety of a combination of the two compounds in persons with amyotrophic lateral sclerosis (ALS) are not known.

Methods: In this multicenter, randomized, double-blind trial, we enrolled participants with definite ALS who had had an onset of symptoms within the previous 18 months.

A systematic review and meta-analysis evaluating geriatric consultation on older trauma patients.

Background: Early involvement of geriatrics is recommended for older trauma patients.

Objective: This systematic review aimed to determine the impact of a geriatric assessment on mortality, hospital length of stay, discharge destination, and delirium incidence in patients 65 years and older admitted to a trauma center.

Methods: The protocol was developed according to Preferred Reporting Items for Systematic Review and Meta-analysis guidelines and registered in PROSPERO (CRD42019131870).

Clinical and Prognostic Impact of a New Left Ventricular Ejection Index in Primary Mitral Regurgitation Because of Mitral Valve Prolapse.

Background: To prevent left ventricular dysfunction (LVD), surgery is recommended in patients with severe primary mitral regurgitation as soon as ejection fraction (EF) ≤60% or LV end-systolic diameter ≥40 mm. However, LVD may be concealed behind preoperative normal LVEF and LV end-systolic diameter. We sought to identify whether a new composite echocardiographic Doppler marker of the LV ejection according to the LV dilatation may predict postoperative LVD and outcome after mitral valve repair in patients with primary mitral regurgitation.

Atrioventricular node ablation in Langendorff-perfused porcine hearts using carbon ion particle therapy: methods and an in vivo feasibility investigation for catheter-free ablation of cardiac arrhythmias.

Background: Particle therapy, with heavy ions such as carbon-12 ((12)C), delivered to arrhythmogenic locations of the heart could be a promising new means for catheter-free ablation. As a first investigation, we tested the feasibility of in vivo atrioventricular node ablation, in Langendorff-perfused porcine hearts, using a scanned 12C beam.

Methods And Results: Intact hearts were explanted from 4 (30-40 kg) pigs and were perfused in a Langendorff organ bath.

Expression of Japanese encephalitis virus antigens in Escherichia coli.

The expression of Japanese encephalitis virus (JE) cDNA in Escherichia coli has been used to study the functional organization of the viral genome. JE protein coding sequences were expressed in E. coli by subcloning random fragments of cloned cDNA (P.