Clinical bioinformatics desiderata for molecular tumor boards.

Clinical Bioinformatics is a knowledge framework required to interpret data of medical interest via computational methods. This area became of dramatic importance in precision oncology, fueled by cancer genomic profiling: most definitions of Molecular Tumor Boards require the presence of bioinformaticians. However, all available literature remained rather vague on what are the specific needs in terms of digital tools and expertise to tackle and interpret genomics data to assign novel targeted or biomarker-driven targeted therapies to cancer patients.

Impact of Measurement Uncertainty on Fault Diagnosis Systems: A Case Study on Electrical Faults in Induction Motors.

Classification systems based on machine learning (ML) models, critical in predictive maintenance and fault diagnosis, are subject to an error rate that can pose significant risks, such as unnecessary downtime due to false alarms. Propagating the uncertainty of input data through the model can define confidence bands to determine whether an input is classifiable, preferring to indicate a result of unclassifiability rather than misclassification. This study presents an electrical fault diagnosis system on asynchronous motors using an artificial neural network (ANN) model trained with vibration measurements.

Zincblende InAsP/InP Quantum Dot Nanowires for Telecom Wavelength Emission.

InAsP quantum dots (QDs) in InP nanowires (NWs) have been realized as a platform for emission at telecom wavelengths. These QDs are typically grown in NWs with the wurtzite crystal phase, but in this case, ultrathin diameters are required to achieve defect-free heterostructures, making the structures less robust. In this work, we demonstrate the growth of pure zincblende InAsP QDs in InP NWs, which enabled an increase in NW diameters to about 45 nm, achieved by employing Au-assisted vapor liquid solid growth in a chemical beam epitaxy system.

Benchmarking and improving the performance of variant-calling pipelines with RecallME.

Motivation: The steady increment of Whole Genome/Exome sequencing and the development of novel Next Generation Sequencing-based gene panels requires continuous testing and validation of variant calling (VC) pipelines and the detection of sequencing-related issues to be maintained up-to-date and feasible for the clinical settings. State of the art tools are reliable when used to compute standard performance metrics. However, the need for an automated software to discriminate between bioinformatic and sequencing issues and to optimize VC parameters remains unmet.

Preexisting Immunity Drives the Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma.

Unlabelled: Current treatment for patients with locally advanced esophageal adenocarcinoma (EAC) is neoadjuvant chemotherapy (nCT), alone or combined with radiotherapy, before surgery. However, fewer than 30% of treated patients show a pathologic complete response to nCT, which correlates with increased 5-year survival compared with nonresponders. Understanding the mechanisms of response to nCT is pivotal to better stratify patients and inform more efficacious therapies.

A New NILM System Based on the SFRA Technique and Machine Learning.

In traditional nonintrusive load monitoring (NILM) systems, the measurement device is installed upstream of an electrical system to acquire the total aggregate absorbed power and derive the powers absorbed by the individual electrical loads. Knowing the energy consumption related to each load makes the user aware and capable of identifying malfunctioning or less-efficient loads in order to reduce consumption through appropriate corrective actions. To meet the feedback needs of modern home, energy, and assisted environment management systems, the nonintrusive monitoring of the power status (ON or OFF) of a load is often required, regardless of the information associated with its consumption.

LncRNA EPR regulates intestinal mucus production and protects against inflammation and tumorigenesis.

The long non-coding RNA EPR is expressed in epithelial tissues, binds to chromatin and controls distinct biological activities in mouse mammary gland cells. Because of its high expression in the intestine, in this study we have generated a colon-specific conditional targeted deletion (EPR cKO) to evaluate EPR in vivo functions in mice. EPR cKO mice display epithelium hyperproliferation, impaired mucus production and secretion, as well as inflammatory infiltration in the proximal portion of the large intestine.

Online SFRA for Reliability of Power Systems: Characterization of a Batch of Healthy and Damaged Induction Motors for Predictive Maintenance.

Asynchronous motors represent a large percentage of motors used in the electrical industry. Suitable predictive maintenance techniques are strongly required when these motors are critical in their operations. Continuous non-invasive monitoring techniques can be investigated to avoid the disconnection of the motors under test and service interruption.

LncRNA EPR-induced METTL7A1 modulates target gene translation.

EPR is a long non-coding RNA (lncRNA) that controls cell proliferation in mammary gland cells by regulating gene transcription. Here, we report on Mettl7a1 as a direct target of EPR. We show that EPR induces Mettl7a1 transcription by rewiring three-dimensional chromatin interactions at the Mettl7a1 locus.

Corrigendum to: 'Mini-Max' knotless acetabular labrum repair: repair construct rationale and allocation in a consecutive case series with minimum 1-year clinical outcomes.

[This corrects the article DOI: 10.1093/jhps/hnab061.].

'Mini-Max' knotless acetabular labrum repair: repair construct rationale and allocation in a consecutive case series with minimum 1-year clinical outcomes.

To describe the 'mini-Max' approach to labrum repair using non-absorbable 2.4-mm knotless suture anchors and report objective clinical outcomes with a large single-surgeon cohort. Level 3 retrospective case series.

Prospective Validation of the Italian Alliance Against Cancer Lung Panel in Patients With Advanced Non-Small-Cell Lung Cancer.

Background: The deeper knowledge of non-small-cell lung cancer (NSCLC) biology and the discovery of driver molecular alterations have opened the era of precision medicine in lung oncology, thus significantly revolutionizing the diagnostic and therapeutic approach to NSCLC. In Italy, however, molecular assessment remains heterogeneous across the country, and numbers of patients accessing personalized treatments remain relatively low. Nationwide programs have demonstrated that the creation of consortia represent a successful strategy to increase the number of patients with a molecular classification.

Next Generation Sequencing in Non-Small Cell Lung Cancer: Pitfalls and Opportunities.

Lung cancer remains the first cause of cancer-related deaths worldwide. Thanks to the improvement in the knowledge of the biology of non-small cell lung cancer (NSCLC), patients' survival has significantly improved. A growing number of targetable molecular alterations have been identified.

Systematic Approach toward Accurate and Efficient DNA Sequencing via Nanoconfinement.

Coarse-grained modeling tools are employed to simulate the mechanics of DNA loading within a nanoscale confinement and predict semiflexible polymer conformations within the confinement, providing design recommendations for DNA-sequencing devices. A workflow is developed to quantify competing requirements of efficiency and accuracy and extract metrics that guide design optimization. The mean first-passage time for DNA loading is calculated as a function of the nanochannel geometry and the applied electric field.

Arthroscopic Capsular Management of the Hip: A Comparison of Indications for and Clinical Outcomes of Periportal Versus Interportal Capsulotomy.

Purpose: To compare the clinical outcomes of periportal capsulotomy versus interportal capsulotomy with closure using a standard clinical algorithm at a minimum of 2 years after hip arthroscopy.

Methods: A retrospective cohort study of patients treated from July 2015 to October 2017 was conducted to determine the effects of 2 capsular management approaches on clinical outcomes. When patient pathology limited adequate exposure via periportal capsulotomy, an interportal capsulotomy was performed.

Comprehensive multi-omics analysis uncovers a group of TGF-β-regulated genes among lncRNA EPR direct transcriptional targets.

Long non-coding RNAs (lncRNAs) can affect multiple layers of gene expression to control crucial cellular functions. We have previously demonstrated that the lncRNA EPR, by controlling gene expression at different levels, affects cell proliferation and migration in cultured mammary gland cells and impairs breast tumor formation in an orthotopic transplant model in mice. Here, we used ChIRP-Seq to identify EPR binding sites on chromatin of NMuMG mammary gland cells overexpressing EPR and identified its trans binding sites in the genome.

β-arrestin1/YAP/mutant p53 complexes orchestrate the endothelin A receptor signaling in high-grade serous ovarian cancer.

The limited clinical response observed in high-grade serous ovarian cancer (HG-SOC) with high frequency of TP53 mutations (mutp53) might be related to mutp53-driven oncogenic pathway network. Here we show that β-arrestin1 (β-arr1), interacts with YAP, triggering its cytoplasmic-nuclear shuttling. This interaction allows β-arr1 to recruit mutp53 to the YAP-TEAD transcriptional complex upon activation of endothelin-1 receptors (ET-1R) in patient-derived HG-SOC cells and in cell lines bearing mutp53.

LncRNA EPR controls epithelial proliferation by coordinating Cdkn1a transcription and mRNA decay response to TGF-β.

Long noncoding RNAs (lncRNAs) are emerging as regulators of fundamental biological processes. Here we report on the characterization of an intergenic lncRNA expressed in epithelial tissues which we termed EPR (Epithelial cell Program Regulator). EPR is rapidly downregulated by TGF-β and its sustained expression largely reshapes the transcriptome, favors the acquisition of epithelial traits, and reduces cell proliferation in cultured mammary gland cells as well as in an animal model of orthotopic transplantation.

Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation.

Transplantation of hematopoietic cells from a healthy individual (allogeneic hematopoietic cell transplantation (allo-HCT)) demonstrates that adoptive immunotherapy can cure blood cancers: still, post-transplantation relapses remain frequent. To explain their drivers, we analyzed the genomic and gene expression profiles of acute myeloid leukemia (AML) blasts purified from patients at serial time-points during their disease history. We identified a transcriptional signature specific for post-transplantation relapses and highly enriched in immune-related processes, including T cell costimulation and antigen presentation.

A Contact Pressure Analysis Comparing an All-Inside and Inside-Out Surgical Repair Technique for Bucket-Handle Medial Meniscus Tears.

Purpose: To directly compare effectiveness of the inside-out and all-inside medial meniscal repair techniques in restoring native contact area and contact pressure across the medial tibial plateau at multiple knee flexion angles.

Methods: Twelve male, nonpaired (n = 12), fresh-frozen human cadaveric knees underwent a series of 5 consecutive states: (1) intact medial meniscus, (2) MCL tear and repair, (3) simulated bucket-handle longitudinal tear of the medial meniscus, (4) inside-out meniscal repair, and (5) all-inside meniscal repair. Knees were loaded with a 1,000-N axial compressive force at 5 knee flexion angles (0°, 30°, 45°, 60°, 90°), and contact area, mean contact pressure, and peak contact pressure were calculated using thin film pressure sensors.

Pharmacokinetics, pharmacodynamics, and tolerability of verinurad, a selective uric acid reabsorption inhibitor, in healthy adult male subjects.

Purpose: Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in clinical development for the treatment of gout and asymptomatic hyperuricemia. The aim of this study was to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of verinurad in healthy adult males.

Subjects And Methods: This was a Phase I, randomized, double-blind, placebo-controlled, single and multiple ascending dose study.