An 18-yr-old man with a history of intellectual disability, craniofacial dysmorphism, seizure disorder, and obesity was identified to carry a de novo, pathogenic variant in ASXL1 (c.4198G>T; p.E1400X) associated with the diagnosis of Bohring–Opitz syndrome based on exome sequencing. In addition, he was identified to carry a maternally inherited and likely pathogenic variant in MC4R (c.817C>T; p.Q273X) associated with monogenic obesity. Dual genetic diagnosis occurs in 4%–6% of patients and results in unique clinical phenotypes that are a function of tissue-specific gene expression, involved pathways, clinical expressivity, and penetrance. This case highlights the utility of next-generation sequencing in patients with an unusual combination of clinical presentations for several pillars of precision medicine including (1) diagnosis, (2) prognosis and outcome, (3) management and therapy, and (4) utilization of resources.

8p11 myeloproliferative syndrome (EMS) represents a unique World Health Organization (WHO)-classified hematologic malignancy defined by translocations of the FGFR1 receptor. The syndrome is a myeloproliferative neoplasm characterized by eosinophilia and lymphadenopathy, with risk of progression to either acute myeloid leukemia (AML) or T- or B-lymphoblastic lymphoma/leukemia. Within the EMS subtype, translocations between breakpoint cluster region (BCR) and fibroblast growth factor receptor 1 (FGFR1) have been shown to produce a dominant fusion protein that is notoriously resistant to tyrosine kinase inhibitors (TKIs). Here, we report two cases of BCR–FGFR1⁺ EMS identified via RNA sequencing (RNA-seq) and confirmed by fluorescence in situ hybridization (FISH). Sanger sequencing revealed that both cases harbored the exact same breakpoint. In the first case, the patient presented with AML-like disease, and in the second, the patient progressed to B-cell acute lymphoblastic leukemia (B-ALL). Additionally, we observed that that primary leukemia cells from Case 1 demonstrated sensitivity to the tyrosine kinase inhibitors ponatinib and dovitinib that can target FGFR1 kinase activity, whereas primary cells from Case 2 were resistant to both drugs. Taken together, these results suggest that some but not all BCR–FGFR1 fusion positive leukemias may respond to TKIs that target FGFR1 kinase activity.

Wilms tumor (WT) is the most common renal malignancy of childhood and accounts for 6% of all childhood malignancies. With current therapies, the 5-yr overall survival (OS) for children with unilateral favorable histology WT is greater than 85%. The prognosis is worse, however, for the roughly 15% of patients who relapse, with only 50%–80% OS reported in those with recurrence. Herein, we describe the extended and detailed clinical course of a rare case of a child with recurrent, pulmonary metastatic, favorable histology WT harboring a BRAF V600E mutation. The BRAF V600E mutation, commonly found in melanoma and other cancers, and previously undescribed in WT, has recently been reported by our group in a subset of epithelial-predominant WT. This patient, who was included in that series, presented with unilateral, stage 1, favorable histology WT and was treated with standard chemotherapy. Following the completion of therapy, the patient relapsed with pulmonary metastatic disease, that then again recurred despite an initial response to salvage chemotherapy and radiation. Next-generation sequencing (NGS) on the metastatic pulmonary nodule revealed a BRAF V600E mutation. After weighing the therapeutic options, a novel approach with dual BRAF/MEK inhibitor combination therapy was initiated. Complete radiographic response was observed following 4 months of therapy with dabrafenib and trametinib. At 12 months following the start of BRAF/MEK combination treatment, the patient continues with a complete response and has experienced minimal treatment-related side effects. This represents the first case, to our knowledge, of effective treatment with BRAF/MEK molecularly targeted therapy in a pediatric Wilms tumor patient.

Clinical benefit of immune checkpoint blockade in glioblastoma (GBM) is rare, and we hypothesize that tumor clonal evolution and the immune microenvironment are key determinants of response. Here, we present a detailed molecular characterization of the intratumoral and immune heterogeneity in an IDH wild-type, MGMT-negative GBM patient who plausibly benefited from anti-PD-1 therapy with an unusually long 25-mo overall survival time. We leveraged multiplex immunohistochemistry, RNA-seq, and whole-exome data from the primary tumor and three resected regions of recurrent disease to survey regional tumor-immune interactions, genomic instability, mutation burden, and expression profiles. We found significant regional heterogeneity in the neoantigenic and immune landscape, with a differential T-cell signature among recurrent sectors, a uniform loss of focal amplifications in EGFR, and a novel subclonal EGFR mutation. Comparisons with recently reported correlates of checkpoint blockade in GBM and with TCGA-GBM revealed appreciable intratumoral heterogeneity that may have contributed to a differential PD-1 blockade response.

People with type 1 diabetes may receive a significant portion of their care from primary care providers (PCPs). To understand the involvement of PCPs in delivering type 1 diabetes care, we performed surveys in California and Florida, two of the most populous and diverse states in the United States. PCPs fill insulin prescriptions but report low confidence in providing type 1 diabetes care and difficulty accessing specialty referrals to endocrinologists.

Background:

Colonoscopy follow-up recommendations depend on the presence or absence of polyps, and if found, their number, size, and histology. Patients may be responsible for conveying results between primary and specialty care or providing medical information to family members; thus, accurate reporting is critical. This analysis assessed the accuracy of self-reported colonoscopy findings.

BACKGROUND AND PURPOSE:

Diffuse intrinsic pontine glioma is a lethal childhood brain cancer with dismal prognosis and MR imaging is the primary methodology used for diagnosis and monitoring. Our aim was to determine whether advanced diffusion, perfusion, and permeability MR imaging metrics predict survival and pseudoprogression in children with newly diagnosed diffuse intrinsic pontine glioma.

Personally, I welcome whatever reality TV drivel Twitch dreams up to feed our insatiable appetite for content.

"This government has failed to show any self-criticism whatsoever, when it is glaringly obvious to everybody that big mistakes have been made."

Boba Fett has been on Lucasfilm’s to-do list for a while now.

Destiny 2 Trials of Osiris returns once again later today – here's what you need to know for this week's end-game PvP challenge.

THE SCOTTISH Government is reviewing its Covid-19 testing strategy after the Deputy First Minster has been left “frustrated” by reports home care workers have been told to travel to the other side of Scotland for tests.

Study highlights industry failures and calls for shift in consumer attitudes

The fashion industry needs to fundamentally change in order to mitigate the environmental impact of fast fashion, experts have said.

Clothes rental, better recycling processes, pollution control technology and the innovative use of offcuts are among measures that could help, they said.

Hollywood loves a good comeback, and post-coronavirus will be no exception, writes costume designer Kristin M Burke

Many events have killed the film industry: the 1918 influenza epidemic, the second world war, the invention of television, the invention of VCRs, the invention of the internet, 9-11, strike after strike after strike. And yet, like a phoenix, it rises, every time stronger than before. The appetite for its product is insatiable especially in times of political trouble and uncertainty about the future. People want to escape. They want to be entertained.

The way we make movies most certainly must change. In the best of circumstances, we are a crew of 75 people jammed into a room with very little ventilation, holding our breath until we hear “CUT”. We are in close contact with one another all day long. We never really thought about it before. All of that is about to change. Film sets usually function as big families, and moving forward, that family unit will take on a stronger, protective meaning. This is how we self-regulate in the post-pandemic era.

Audio of a private conversation shows the 44th president's unvarnished views about the former national security adviser's case and the White House's COVID-19 response.

More than 20 million Americans lost their jobs in the last month, and unemployment among African-Americans has hit 16.7 percent.

The U.S. Centers for Disease Control and Prevention (CDC) on Friday reported 1,248,040 cases of the new coronavirus, an increase of 28,974 cases from its previous count, and said that the number of deaths had risen by 2,180 to 75,477.

As Quebec prepares to reopen schools, doctors are poring over 15-20 cases of children with what seems to be the same illnesses reported in U.S. and Europe

The Italian is reportedly set to leave Stamford Bridge at the end of his contract..

Stay home, keep gaming

BALTIMORE (AP) - Brutal. Horrific. Tragic.

Choose your description. The April jobs report showed, in harrowing detail, just how terribly the coronavirus outbreak has pummeled the U.S. economy. Most obviously, there's the 14.7% unemployment rate, the highest since the Great Depression. And the shedding of more than 20 million jobs, ...

Gas cookers making people sick and exposing tens of millions to air pollution levels that would be illegal if they were outside

Gas stoves are making people sick, contributing pollution that makes indoor air up to two to five times dirtier than outdoor air, according to a new report.

Related: Microplastics found in greater quantities than ever before on seabed

While NBA teams are slowly gearing up to return to training facilities this week, the league has reportedly issued a memo prohibiting those with elevated temperatures from participating.  

Super Bowl champion quarterback Joe Flacco underwent neck surgery last month and is expected to be out until September, according to multiple reports.

Baltimore Ravens safety Earl Thomas appears to have reconciled with his wife after reports emerged earlier this week that she held him at gunpoint last month after discovering an alleged affair. 

It's the lowest reported increase in cases since April 6.

CEO Tim Cook talked at least as much about COVID-19 efforts as the business itself.

Azure's still going strong, and even Xbox avoided major losses.

Magician Roy Horn, who alongside Siegfried Fischbacher starred in a popular, long-running Las Vegas act built around rare tigers, died on Friday from of complications of COVID-19, the Las Vegas Review-Journal newspaper reported. He was 75.

Read our live updates on coronavirus HERE Coronavirus: The symptoms

Read our live updates on coronavirus HERE Coronavirus: The symptoms

Follow our live coronavirus updates here Coronavirus: the symptoms

Downing Street has fiercely rebuffed newspaper reports that Boris Johnson failed to act in the early stages of the coronavirus outbreak.

A major study has deemed increasing testing and contact tracing in the community the "most promising approach" to lifting coronavirus lockdown measures in the short term.

Follow our live coronavirus updates here

2019 was the hottest year on record for Europe as global warming trends continue, major analysis has shown.

Health bosses have denied a report that transfers of coronavirus patients to the newly built NHS Nightingale in London were rejected due to a lack of nurses.

The true number of deaths linked to coronavirus in the UK is at least 5,000 higher than those reported from hospitals, new figures show.

The Foreign Secretary has confirmed the Government is following reports of Kim Jong Un's death "very closely".

The death toll linked to coronavirus in England is around 40 per cent higher than previously reported, new figures show.

Twitter users have been complaining that their direct messaging function (DMs) is down.

Not for one Spanish TV anchor, whose video-chat blunder might have cost him his relationship.

Nigel Farage has been visited by police officers who advised him not to breach lockdown restrictions after he travelled to Dover to report on migrants.

Hundreds of O2 and Vodafone customers have reported problems with the networks.

Public Health England medical director Professor Yvonne Doyle said it was "too early" to compare the UK statistics with that of other countries.

The UK was ill-prepared to deal with a health pandemic, according to a secret Whitehall document produced years before the coronavirus outbreak.

Posts from high-profile accounts tout questionable virus therapies and cures.