Artificial intelligence and the future of life sciences.

Over the past few decades, the number of health and 'omics-related data' generated and stored has grown exponentially. Patient information can be collected in real time and explored using various artificial intelligence (AI) tools in clinical trials; mobile devices can also be used to improve aspects of both the diagnosis and treatment of diseases. In addition, AI can be used in the development of new drugs or for drug repurposing, in faster diagnosis and more efficient treatment for various diseases, as well as to identify data-driven hypotheses for scientists.

Skin disease is more recalcitrant than muscle disease: A long-term prospective study of 184 children with juvenile dermatomyositis.

Background: Persistent skin manifestations, especially calcinoses, contribute to morbidity in children with juvenile dermatomyositis.

Objective: To compare the course of skin and muscle involvement and document frequency of calcinosis in juvenile dermatomyositis.

Methods: Prospective cohort study of 184 untreated children with juvenile dermatomyositis (July 1971 to May 2019) at a single children's hospital.

Effect of allogeneic mesenchymal stem cells (MSCs) on corneal wound healing in dogs.

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Antifungal drugs: New insights in research & development.

The need for better antifungal therapy is commonly accepted in view of the high mortality rates associated with systemic infections, the low number of available antifungal classes, their associated toxicity and the increasing number of infections caused by strains with natural or acquired resistance. The urgency to expand the range of therapeutic options for the treatment of fungal infections has led researchers in recent decades to seek alternative antifungal targets when compared to the conventional ones currently used. Although new potential targets are reported, translating the discoveries from bench to bedside is a long process and most of these drugs fail to reach the patients.

Recommendations for pharmacological clinical trials in children with functional constipation: The Rome foundation pediatric subcommittee on clinical trials.

Background: Evidence for the efficacy of commonly used drugs in the treatment of childhood functional constipation (FC) is scarce, studies are often of low quality and study designs are heterogeneous. Thus, recommendations for the design of clinical trials in childhood FC are needed.

Purpose: Members of the Rome Foundation and a member of the Pediatric Committee of the European Medicines Agency formed a committee to create recommendations for the design of clinical trials in children with FC.

Age 4 Predictors of Oppositional Defiant Disorder in Early Grammar School.

Our ability to predict which children will exhibit oppositional defiant disorder (ODD) at the time of entry into grammar school at age 6 lags behind our understanding of the risk factors for ODD. This study examined how well a set of multidomain risk factors for ODD assessed in 4-year-old children predicted age 6 ODD diagnostic status. Participants were a diverse sample of 796 4-year-old children (391 boys).

Robust stratification of breast cancer subtypes using differential patterns of transcript isoform expression.

Breast cancer, the second leading cause of cancer death of women worldwide, is a heterogenous disease with multiple different subtypes. These subtypes carry important implications for prognosis and therapy. Interestingly, it is known that these different subtypes not only have different biological behaviors, but also have distinct gene expression profiles.

Folate receptor alpha is more than just a folate transporter.

Until recently folate receptor alpha (FRα) has only been considered as a folate transporter. However, a novel role of FRα as a transcription factor was reported by our lab. More recently our lab showed a novel pleiotropic role of FRα: (a) direct transcriptional activation of , and genes; and (b) repression of biogenesis of miRNAs that target these genes or their effector molecules.

Worse prognosis in breast cancer patients can be predicted by immunohistochemical analysis of positive MMP-2 and negative estrogen and progesterone receptors.

Introduction:: Breast cancer is the most cause of death, and approximately 90% of these deaths are due to metastases. Matrix metalloproteinase-2 (MMP-2) gelatinase activity is able to degrade a major constituent of the tumor microenvironment, type IV collagen. Two well-established proteins used as markers in clinical practice for breast cancer are the receptors for estrogen (ER) and progesterone (PR).

Expression of miR-18a and miR-210 in Normal Breast Tissue as Candidate Biomarkers of Breast Cancer Risk.

miRNAs are noncoding RNAs with abnormal expression in breast cancer; their expression in high-risk benign breast tissue may relate to breast cancer risk. We examined miRNA profiles in contralateral unaffected breasts (CUB) of patients with breast cancer and validated resulting candidates in two additional sample sets. Expression profiles of 754 mature miRNAs were examined using TaqMan Low Density Arrays in 30 breast cancer samples [15 estrogen receptor (ER)-positive and 15 ER-negative] and paired CUBs and 15 reduction mammoplasty controls.

Recommendations for pharmacological clinical trials in children with irritable bowel syndrome: the Rome foundation pediatric subcommittee on clinical trials.

Background: There is little published evidence of efficacy for the most commonly used treatments. Thus, there is an urgent need to conduct clinical trials on existing and novel therapies.

Purpose: In order to address these issues the Rome Foundation and members of the Pediatric Committee of the European Medicines Agency formed a subcommittee on clinical trials to develop guidelines for the design of clinical trials in children with irritable bowel syndrome (IBS).

The Use of Ultrasound Guidance for Perioperative Neuraxial and Peripheral Nerve Blocks in Children: A Cochrane Review.

Background: Objectives were to determine whether the use of ultrasound guidance offers any clinical advantage in the performance of neuraxial or peripheral nerve blocks in children in terms of increasing the success rate or decreasing the rate of complications.

Methods: We searched the following databases to March 2015: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OvidSP), EMBASE (OvidSP), and Scopus (to January 2015). We included all parallel randomized controlled trials that evaluated the effect of ultrasound guidance to perform a regional blockade technique in children.

Identification of TMEM230 mutations in familial Parkinson's disease.

Parkinson's disease is the second most common neurodegenerative disorder without effective treatment. It is generally sporadic with unknown etiology. However, genetic studies of rare familial forms have led to the identification of mutations in several genes, which are linked to typical Parkinson's disease or parkinsonian disorders.

Absence of UCHL 1 function leads to selective motor neuropathy.

Objective: The aim of this study was to investigate the role of ubiquitin C-terminal hydrolase-L1 (UCHL1) for motor neuron circuitry and especially in spinal motor neuron (SMN) health, function, and connectivity.

Methods: Since mutations in UCHL1 gene leads to motor dysfunction in patients, we investigated the role of UCHL1 on SMN survival, axon health, and connectivity with the muscle, by employing molecular and cellular marker expression analysis and electrophysiological recordings, in healthy wild-type and Uchl1 (nm3419) (UCHL1-/-) mice, which lack all UCHL1 function.

Results: There is pure motor neuropathy with selective degeneration of the motor, but not sensory axons in the absence of UCHL1 function.

Small Intestine Early Innate Immunity Response during Intestinal Colonization by Escherichia coli Depends on Its Extra-Intestinal Virulence Status.

Uropathogenic Escherichia coli (UPEC) strains live as commensals in the digestive tract of the host, but they can also initiate urinary tract infections. The aim of this work was to determine how a host detects the presence of a new UPEC strain in the digestive tract. Mice were orally challenged with UPEC strains 536 and CFT073, non-pathogenic strain K12 MG1655, and ΔPAI-536, an isogenic mutant of strain 536 lacking all 7 pathogenicity islands whose virulence is drastically attenuated.

Pain Measurement in Children with Functional Abdominal Pain.

Functional abdominal pain (FAP) occurs frequently in pediatric patients. Lacking clear biomarkers, clinicians and researchers must rely on patient reports of pain intensity. Presently, there are challenges affecting our ability to use existing measures of self-reported pediatric pain intensity.

Systematic Review: Issues in Measuring Clinically Meaningful Change in Self-Reported Chronic Pediatric Pain Intensity.

Objective: This report examined limitations in our ability to assess clinically significant change (CSC) in randomized controlled trials of treatments of self-reported pediatric chronic pain intensity.

Methods: The following were reviewed: (a) approaches to assessing CSC; (b) approaches to assessing CSC used in psychological treatment studies of self-reported pediatric chronic pain intensity included in a recent systematic review; (c) the role of test-retest reliability in distribution-based CSC measures; (d) the test-retest reliability of recommended chronic pain measures.

Results And Conclusions: Existing studies do not assess whether a CSC occurred or use procedures that did not account for measurement error and true score fluctuations unrelated to treatment, possibly resulting in overestimating CSCs.

Healthy and diseased corticospinal motor neurons are selectively transduced upon direct AAV2-2 injection into the motor cortex.

Direct gene delivery to the neurons of interest, without affecting other neuron populations in the cerebral cortex, represent a challenge owing to the heterogeneity and cellular complexity of the brain. Genetic modulation of corticospinal motor neurons (CSMN) is required for developing effective and long-term treatment strategies for motor neuron diseases, in which voluntary movement is impaired. Adeno-associated viruses (AAV) have been widely used for neuronal transduction studies owing to long-term and stable gene expression as well as low immunoreactivity in humans.

Regulatory variant in FZD6 gene contributes to nonsyndromic cleft lip and palate in an African-American family.

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect affecting 135,000 newborns worldwide each year. While a multifactorial etiology has been suggested as the cause, despite decades of research, the genetic underpinnings of NSCLP remain largely unexplained. In our previous genome-wide linkage study of a large NSCLP African-American family, we identified a candidate locus at 8q21.

Excessive Wnt/beta-catenin signaling promotes midbrain floor plate neurogenesis, but results in vacillating dopamine progenitors.

The floor plate (FP), a ventral midline structure of the developing neural tube, has differential neurogenic capabilities along the anterior-posterior axis. The midbrain FP, unlike the hindbrain and spinal cord floor plate, is highly neurogenic and produces midbrain dopaminergic (mDA) neurons. Canonical Wnt/beta-catenin signaling, at least in part, is thought to account for the difference in neurogenic capability.

Abdominal pain endpoints currently recommended by the FDA and EMA for adult patients with irritable bowel syndrome may not be reliable in children.

Background: The Food and Drug Administration (FDA) recommended ≥30% decrease on patient-reported outcomes for pain be considered clinically significant in clinical trials for adults with irritable bowel syndrome. This percent change approach may not be appropriate for children. We compared three alternate approaches to determining clinically significant reductions in pain among children.

Epigenomes as therapeutic targets.

Epigenetics is a molecular phenomenon that pertains to heritable changes in gene expression that do not involve changes in the DNA sequence. Epigenetic modifications in a whole genome, known as the epigenome, play an essential role in the regulation of gene expression in both normal development and disease. Traditional epigenetic changes include DNA methylation and histone modifications.

Assessing cardiomyocyte proliferative capacity in the newt heart and primary culture.

Unlike humans, adult newts possess extraordinary abilities to functionally regenerate lost and injured organs, including cardiac muscle. The most remarkable feature of mature newt cardiomyocytes is their ability to reenter the cell cycle, undergo cell division, and serve as a reservoir for progenitor cells. There are, however, a number of unsolved questions concerning the cellular and molecular mechanisms that underlie this plasticity; for example, we still lack a deeper understanding of the cell-inherent properties of newt cardiomyocytes and to what degree they differ from their mammalian counterparts.

Maintaining Eastern newts (Notophthalmus viridescens) for regeneration research.

The adult Eastern newt, Notophthalmus viridescens, has long served as a model for appendage as well as heart muscle regeneration studies. Newt tissues include all major cell types known in other vertebrates and mammals, including bone, cartilage, tendon, muscle, nerves, dermis, and epidermis. Therefore, these aquatic salamanders make an excellent model for studying the regeneration of complex tissues.