Comparison of tumor-associated YAP1 fusions identifies a recurrent set of functions critical for oncogenesis.

YAP1 is a transcriptional coactivator and the principal effector of the Hippo signaling pathway, which is causally implicated in human cancer. Several gene fusions have been identified in various human cancers and identifying the essential components of this family of gene fusions has significant therapeutic value. Here, we show that the gene fusions , , , and are oncogenic in mice.

High Frequency of Shared Clonotypes in Human T Cell Receptor Repertoires.

The collection of T cell receptors (TCRs) generated by somatic recombination is large but unknown. We generate large TCR repertoire datasets as a resource to facilitate detailed studies of the role of TCR clonotypes and repertoires in health and disease. We estimate the size of individual human recombined and expressed TCRs by sequence analysis and determine the extent of sharing between individual repertoires.

Incidence of diabetes and prediabetes and predictors of glycemic change among South Asians in the USA: the MASALA study.

Introduction: South Asians have a high prevalence of type 2 diabetes mellitus (T2DM). This may be associated with high rates of conversion through the natural history of disease. However, there is a paucity of data on prediabetes and T2DM incidence and related predictors in South Asians in the USA.

Outcomes of T-lymphoblastic lymphoma treated with pediatric ALL-like protocol.

Background: The management of T-lymphoblastic lymphoma (T-LBL) in adults poses uncertainties, including optimal chemotherapy regimen, need for radiotherapy, and the benefit of stem cell transplant. This retrospective case series investigated the efficacy of the pediatric BFM-90 regimen in adult patients and evaluated the role of early response assessment by positron emission tomography with computed tomography (PET-CT) in predicting outcomes.

Methods: Patients aged 15 years or older with T-LBL diagnosed at Tata Memorial Hospital, Mumbai, India were given chemotherapy according to the European BFM-90 protocol (n = 38).

Correlation Between FDG Hotspots on Pre-radiotherapy PET/CT and Areas of HNSCC Local Relapse: Impact of Treatment Position and Images Registration Method.

Several series have already demonstrated that intratumoral subvolumes with high tracer avidity (hotspots) in 18F-flurodesoxyglucose positron-emission tomography (FDG-PET/CT) are preferential sites of local recurrence (LR) in various solid cancers after radiotherapy (RT), becoming potential targets for dose escalation. However, studies conducted on head and neck squamous cell carcinoma (HNSCC) found only a moderate overlap between pre- and post-treatment subvolumes. A limitation of these studies was that scans were not performed in RT treatment position (TP) and were coregistred using a rigid registration (RR) method.

Radiotherapy target volume definition in newly diagnosed high grade glioma using F-FET PET imaging and multiparametric perfusion MRI: A prospective study (IMAGG).

Purpose: The aim of this study was to prospectively investigate tumor volume delineation by amino acid PET and multiparametric perfusion magnetic resonance imaging (MRI) in patients with newly diagnosed, untreated high grade glioma (HGG).

Materials And Methods: Thirty patients with histologically confirmed HGG underwent O-(2-[F]-fluoroethyl)-l-tyrosine (F-FET) positron emission tomography (PET), conventional Magnetic Resonance Imaging (MRI) as contrast-enhanced (CE) and fluid-attenuated inversion recovery (FLAIR) and multiparametric MRI as relative cerebral blood volume (rCBV) and permeability estimation map (K2). Areas of MRI volumes were semi-automatically segmented.

Evolutionary and plastic changes in a native annual plant after a historic drought.

Severe droughts are forecast to increase with global change. Approaches that enable the study of contemporary evolution, such as resurrection studies, are valuable for providing insights into the responses of populations to global change. In this study, we used a resurrection approach to study the evolution of the California native (true babystars, Polemoniaceae) across populations differing in precipitation in response to the state's recent prolonged drought (2011-2017).

Pan-cancer analysis of the developmental pathways reveals non-canonical wnt signaling as a driver of mesenchymal-type tumors.

The processes of angiogenesis, cell proliferation, invasion, and migration, and the signaling pathways that drive these events, are activated in both cancer and during embryonic development. Here, we systematically assessed how the activity of major developmental signaling pathways, represented by the expression of genes encoding components of the pathways, correlated with patient survival in ∼8000 patients across 17 cancer types. We also compared the expressed genes enriched in developmental pathways with those associated with epithelial-mesenchymal transition (EMT) both in a cancer cohort and in mice during embryonic development.

Evidence generation, decision making, and consequent growth in health disparities.

Evidence is valuable because it informs decisions to produce better outcomes. However, the same evidence that is complete for some individuals or groups may be incomplete for others, leading to inefficiencies in decision making and growth in disparities in outcomes. Specifically, the presence of treatment effect heterogeneity across some measure of baseline risk, and noisy information about such heterogeneity, can induce self-selection into randomized clinical trials (RCTs) by patients with distributions of baseline risk different from that of the target population.

Flow cytometric evaluation of CD38 expression levels in the newly diagnosed T-cell acute lymphoblastic leukemia and the effect of chemotherapy on its expression in measurable residual disease, refractory disease and relapsed disease: an implication for anti-CD38 immunotherapy.

Background: Recently, anti-CD38 monoclonal antibody (Mab) therapy has become a focus of attention as an additional/alternative option for many hematological neoplasms including T-cell acute lymphoblastic leukemia (T-ALL). It has been shown that antitumor efficacy of anti-CD38-Mab depends on the level of CD38 expression on tumor cells. Reports on CD38 expression in T-ALL are scarce, and data on the effect of cytotoxic chemotherapy on CD38 expression are limited to very few samples.

Impact of suboptimal dosimetric coverage of pretherapeutic 18F-FDG PET/CT hotspots on outcome in patients with locally advanced cervical cancer treated with chemoradiotherapy followed by brachytherapy.

Introduction: Areas of high uptake on pre-treatment F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT), denoted as "hotspots", have been identified as preferential sites of local relapse in locally advanced cervical cancer (LACC). The purpose of this study was to analyze the dosimetric coverage of these hotspots with high dose-rate brachytherapy (BT).

Methods: For each patient, a rigid registration of the CT from the pre-treatment PET/CT with the radiotherapy planning CT was performed using 3D Slicer, followed by a manual volume correction by translation and deformation if necessary.

Non-linear Deep Neural Network for Rapid and Accurate Prediction of Phenotypic Responses to Kinase Inhibitors.

Protein kinase inhibitors are one of the most successful targeted therapies to date. Despite this progress, additional kinase inhibitors are needed to expand the target space as well as overcome drug resistance that has emerged in clinical setting. Here, we developed KiDNN (Kinase inhibitor prediction using Deep Neural Networks).

Measuring Real-time Drug Response in Organotypic Tumor Tissue Slices.

Tumor tissues are composed of cancerous cells, infiltrated immune cells, endothelial cells, fibroblasts, and extracellular matrix. This complex milieu constitutes the tumor microenvironment (TME) and can modulate response to therapy in vivo or drug response ex vivo. Conventional cancer drug discovery screens are carried out on cells cultured in a monolayer, a system critically lacking the influence of TME.

Post-induction Measurable Residual Disease Using Multicolor Flow Cytometry Is Strongly Predictive of Inferior Clinical Outcome in the Real-Life Management of Childhood T-Cell Acute Lymphoblastic Leukemia: A Study of 256 Patients.

Measurable/minimal residual disease (MRD) status is suggested as a powerful indicator of clinical-outcome in T-cell lymphoblastic leukemia/lymphoma (T-ALL). Contrary to B-cell ALL, reports on T-ALL MRD are limited and mostly based on molecular methods, mainly from developed countries. Multicolor flow cytometry (MFC)-based T-ALL studies are very few.

The Th9 Axis Reduces the Oxidative Stress and Promotes the Survival of Malignant T Cells in Cutaneous T-Cell Lymphoma Patients.

Immune dysfunction is critical in pathogenesis of cutaneous T-cell lymphoma (CTCL). Few studies have reported abnormal cytokine profile and dysregulated T-cell functions during the onset and progression of certain types of lymphoma. However, the presence of IL9-producing Th9 cells and their role in tumor cell metabolism and survival remain unexplored.

Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Improving Function While Maintaining Oncologic Outcome.

The improved survival in patients with HPV-positive (human papilloma virus) oropharyngeal squamous cell carcinoma as compared with HPV-negative disease calls for treatment that preserves quality of life, particularly a functional swallow. There are several trials currently assessing treatment de-escalation in terms of less invasive transoral robotic surgery, reduced-dose radiotherapy, and omission of chemotherapy in this disease cohort. It is important for head and neck oncology surgeons to stay abreast of developments in this area to offer their patients the most up-to-date treatment and consider recruiting patients to trials at their institutions.

CD304/neuropilin-1 is a very useful and dependable marker for the measurable residual disease assessment of B-cell precursor acute lymphoblastic leukemia.

Background: Measurable residual disease (MRD) assessment using multicolor flow cytometry (MFC) has become the center point of pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) risk stratification and therapeutic management. The addition of new markers can improve the accuracy and applicability of MFC-based MRD assay further. Herein, we evaluated the utility of a new marker, CD304/neuropilin-1, in the assessment of MFC-based MRD.

Autism risk in offspring can be assessed through quantification of male sperm mosaicism.

De novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception. The recurrence risk for autism spectrum disorders is substantial, leading many families to decline future pregnancies, but the potential impact of assessing parental gonadal mosaicism has not been considered. We measured sperm mosaicism using deep-whole-genome sequencing, for variants both present in an offspring and evident only in father's sperm, and identified single-nucleotide, structural and short tandem-repeat variants.

Survival outcomes for head and neck cancer patients with N3 cervical nodal metastases.

Background: Management of metastatic N3 nodal disease from primary head and neck squamous cell carcinoma (HNSCC) is controversial. Recently, there has been a move to observation of the neck for those who achieve complete response (CR) after chemoradiotherapy (CRT). We sought to determine survival outcomes for N3 nodal disease, particularly for patients with human papilloma virus (HPV)-positive HNSCC.

Clinical profile and management outcomes of traumatic submacular hemorrhage.

Purpose: To evaluate the anatomical and functional outcome of patients with traumatic submacular hemorrhage (SMH).

Methods: A retrospective, interventional case series of patients presenting between January 2016 and April 2018 was carried out at 4 tertiary eye care centers of India. Medical records of the patients with a history of blunt trauma and SMH were retrospectively reviewed.