Value of MRI - T2 Mapping to Differentiate Clinically Significant Prostate Cancer.

Standardized reporting of multiparametric prostate MRI (mpMRI) is widespread and follows international standards (Pi-RADS). However, quantitative measurements from mpMRI are not widely comparable. Although T2 mapping sequences can provide repeatable quantitative image measurements and extract reliable imaging biomarkers from mpMRI, they are often time-consuming.

Novel pathogenic variants in HR underlie atrichia with papular lesions in a cohort of 10 families.

Atrichia with papular lesions (APL) is a hair abnormality characterized by loss of hair on the scalp and rest of the body. In a few cases, hair loss is accompanied by the appearance of keratotic papules on the body. It is inherited in an autosomal recessive manner.

Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release.

Nociceptin/orphanin-FQ (N/OFQ) is a recently appreciated critical opioid peptide with key regulatory functions in several central behavioral processes including motivation, stress, feeding, and sleep. The functional relevance of N/OFQ action in the mammalian brain remains unclear due to a lack of high-resolution approaches to detect this neuropeptide with appropriate spatial and temporal resolution. Here we develop and characterize NOPLight, a genetically encoded sensor that sensitively reports changes in endogenous N/OFQ release.

Significance of utilizing in silico structural analysis and phenotypic data to characterize phenylalanine hydroxylase variants: A PAH landscape.

Phenylketonuria (PKU) is a genetic disorder caused by variations in the phenylalanine hydroxylase (PAH) gene. Among the 3369 reported PAH variants, 33.7% are missense alterations.

Recessive variants in MYO1C as a potential novel cause of proteinuric kidney disease.

Background: Steroid-resistant nephrotic syndrome is the second leading cause of chronic kidney disease among patients < 25 years of age. Through exome sequencing, identification of > 65 monogenic causes has revealed insights into disease mechanisms of nephrotic syndrome (NS).

Methods: To elucidate novel monogenic causes of NS, we combined homozygosity mapping with exome sequencing in a worldwide cohort of 1649 pediatric patients with NS.

Complex structural variation and nonsense variant cause -related disorder.

Homozygous variants have been previously described in two unrelated patients with a neurodevelopmental disorder with microcephaly, seizures and neonatal cholestasis. encodes a subunit that is unique to the heterotetrameric endosome-associated recycling protein (EARP) complex. The other subunits of the EARP complex, such as VPS51, VPS52 and VPS53, are also shared by the Golgi-associated retrograde protein complex.

Elevation of cardiac enzymes and B-type natriuretic peptides following venous recanalization and stenting in chronic venous obstruction.

Background: B-type natriuretic peptides (BNP) and cardiac enzymes are both recognized biomarkers of heart health. Many studies have reported that using these indicators can assess cardiac condition and predict prognosis of patients undergoing surgery. Currently little is known on the effect of increased cardiac input after venous recanalization on cardiac physiology in patients with chronic venous obstruction (CVO).

Phytate metabolism is mediated by microbial cross-feeding in the gut microbiota.

Dietary intake of phytate has various reported health benefits. Previous work showed that the gut microbiota can convert phytate to short-chain fatty acids (SCFAs), but the microbial species and metabolic pathway are unclear. Here we identified Mitsuokella jalaludinii as an efficient phytate degrader, which works synergistically with Anaerostipes rhamnosivorans to produce the SCFA propionate.

Time-Resolved Dynamic Optical Coherence Tomography for Retinal Blood Flow Analysis.

Purpose: Optical coherence tomography (OCT) representations in clinical practice are static and do not allow for a dynamic visualization and quantification of blood flow. This study aims to present a method to analyze retinal blood flow dynamics using time-resolved structural OCT.

Methods: We developed novel imaging protocols to acquire video-rate time-resolved OCT B-scans (1024 × 496 pixels, 10 degrees field of view) at four different sensor integration times (integration time of 44.

Molecular maps of synovial cells in inflammatory arthritis using an optimized synovial tissue dissociation protocol.

In this study, we optimized the dissociation of synovial tissue biopsies for single-cell omics studies and created a single-cell atlas of human synovium in inflammatory arthritis. The optimized protocol allowed consistent isolation of highly viable cells from tiny fresh synovial biopsies, minimizing the synovial biopsy drop-out rate. The synovium scRNA-seq atlas contained over 100,000 unsorted synovial cells from 25 synovial tissues affected by inflammatory arthritis, including 16 structural, 11 lymphoid, and 15 myeloid cell clusters.

Exact Sketch-Based Read Mapping.

Given a sequencing read, the broad goal of read mapping is to find the location(s) in the reference genome that have a "similar sequence". Traditionally, "similar sequence" was defined as having a high alignment score and read mappers were viewed as heuristic solutions to this well-defined problem. For sketch-based mappers, however, there has not been a problem formulation to capture what problem an exact sketch-based mapping algorithm should solve.

Pembrolizumab for advanced urothelial carcinoma: exploratory ctDNA biomarker analyses of the KEYNOTE-361 phase 3 trial.

Circulating tumor DNA (ctDNA) is emerging as a potential biomarker in early-stage urothelial cancer, but its utility in metastatic disease remains unknown. In the phase 3 KEYNOTE-361 study, pembrolizumab with and without chemotherapy was compared with chemotherapy alone in patients with metastatic urothelial cancer. The study did not meet prespecified efficacy thresholds for statistical significance.

Novel biallelic PISD missense variants cause spondyloepimetaphyseal dysplasia with disproportionate short stature and fragmented mitochondrial morphology.

Biallelic variants in PISD cause a phenotypic spectrum ranging from short stature with spondyloepimetaphyseal dysplasia (SEMD) to a multisystem disorder affecting eyes, ears, bones, and brain. PISD encodes the mitochondrial-localized enzyme phosphatidylserine decarboxylase. The PISD precursor is self-cleaved to generate a heteromeric mature enzyme that converts phosphatidylserine to the phospholipid phosphatidylethanolamine.

Clinical genomics expands the link between erroneous cell division, primary microcephaly and intellectual disability.

Primary microcephaly is a rare neurogenic and genetically heterogeneous disorder characterized by significant brain size reduction that results in numerous neurodevelopmental disorders (NDD) problems, including mild to severe intellectual disability (ID), global developmental delay (GDD), seizures and other congenital malformations. This disorder can arise from a mutation in genes involved in various biological pathways, including those within the brain. We characterized a recessive neurological disorder observed in nine young adults from five independent consanguineous Pakistani families.

Reliability of power output, maximal rate of capillary blood lactate accumulation, and phosphagen contribution time following 15-s sprint cycling in amateur cyclists.

Based on Mader's mathematical model, the rate of capillary blood lactate concentration (νLa) following intense exercise is thought to reflect the maximal glycolytic rate. We aimed to investigate the reliability of important variables of Mader's model (i.e.

Phenylbutyrate Treatment in a Boy with MCT8 Deficiency: Improvement of Thyroid Function Tests and Possible Livertoxicity.

Context: Monocarboxylate transporter 8 (MCT8) deficiency is a rare X-chromosomal inherited disease leading to severe cognitive impairment, muscular hypotonia and symptoms of peripheral thyrotoxicosis. Experimental approaches aiming to functionally rescue mutant MCT8 activity by the chemical chaperone phenylbutyrate (PB) demonstrated promising effects in vitro for several MCT8 missense mutations.

Objective: The objective was to evaluate biochemical and clinical effects of PB in doses equivalent to those approved for the treatment of urea cycle disorders in a boy with MCT8 deficiency due to a novel MCT8 missense mutation c.

Development of a long noncoding RNA-based machine learning model to predict COVID-19 in-hospital mortality.

Tools for predicting COVID-19 outcomes enable personalized healthcare, potentially easing the disease burden. This collaborative study by 15 institutions across Europe aimed to develop a machine learning model for predicting the risk of in-hospital mortality post-SARS-CoV-2 infection. Blood samples and clinical data from 1286 COVID-19 patients collected from 2020 to 2023 across four cohorts in Europe and Canada were analyzed, with 2906 long non-coding RNAs profiled using targeted sequencing.

Secukinumab in adult patients with lichen planus: efficacy and safety results from the randomized placebo-controlled proof-of-concept PRELUDE study.

Background: Patients with lichen planus (LP) refractory to available therapies often experience a high disease burden, representing a population with a clear unmet need for new treatments.

Objectives: To evaluate the efficacy and safety of secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven cutaneous LP (CLP), mucosal LP (MLP) or lichen planopilaris (LPP) that is inadequately controlled by topical corticosteroids.

Methods: PRELUDE was a randomized double-blind placebo-controlled phase II proof-of-concept study that enrolled patients with CLP, MLP or LPP.

Next-generation phenotyping in Nigerian children with Cornelia de Lange syndrome.

Next-generation phenotyping (NGP) can be used to compute the similarity of dysmorphic patients to known syndromic diseases. So far, the technology has been evaluated in variant prioritization and classification, providing evidence for pathogenicity if the phenotype matched with other patients with a confirmed molecular diagnosis. In a Nigerian cohort of individuals with facial dysmorphism, we used the NGP tool GestaltMatcher to screen portraits prior to genetic testing and subjected individuals with high similarity scores to exome sequencing (ES).

Diaphragm ultrasound in patients with prolonged weaning from mechanical ventilation.

Background: Several publications have examined diaphragmatic ultrasound using two-dimensional (2D) parameters in the context of weaning from mechanical ventilation (MV) and extubation. However, the studied cohorts had rather short duration of ventilation. Examinations on patients with prolonged weaning after long-term ventilation were missing.