Genomic analysis of a patient's tumor is the cornerstone of precision oncology, but it does not address whether metastases should be treated differently. Here we tested whether comparative single-cell RNA sequencing (scRNA-seq) of a primary small intestinal neuroendocrine tumor to a matched liver metastasis could guide the treatment of a patient's metastatic disease. Following surgery, the patient was put on maintenance treatment with a somatostatin analog. However, the scRNA-seq analysis revealed that the neuroendocrine epithelial cells in the liver metastasis were less differentiated and expressed relatively little SSTR2, the predominant somatostatin receptor. There were also differences in the tumor microenvironments. RNA expression of vascular endothelial growth factors was higher in the primary tumor cells, reflected by an increased number of endothelial cells. Interestingly, vascular expression of the major VEGF receptors was considerably higher in the liver metastasis, indicating that the metastatic vasculature may be primed for expansion and susceptible to treatment with angiogenesis inhibitors. The patient eventually progressed on Sandostatin, and although consideration was given to adding an angiogenesis inhibitor to her regimen, her disease progression involved non-liver metastases that had not been characterized. Although in this specific case comparative scRNA-seq did not alter treatment, its potential to help guide therapy of metastatic disease was clearly demonstrated.

We report the diagnostic challenges and the clinical course of a patient with an extraordinary presentation of B-lymphoblastic leukemia (B-ALL) with eosinophilia. We identified a novel ZBTB20-JAK2 gene fusion as a chimeric RNA transcript using the Archer platform. This gene fusion from the same patient was recently identified by Peterson et al. (2019) at the genomic level using a different sequencing technology platform. The configuration of this gene fusion predicts the production of a kinase-activating JAK2 fusion protein, which would normally lead to a diagnosis of Philadelphia chromosome–like B-ALL (Ph-like B-ALL). However, the unusual presentation of eosinophilia led us to demonstrate the presence of this gene fusion in nonlymphoid hematopoietic cells by fluorescence in situ hybridization (FISH) studies with morphologic correlation. Therefore, we believe this disease, in fact, represents blast crisis arising from an underlying myeloid neoplasm with JAK2 rearrangements. This case illustrates the difficulty in differentiating Ph-like B-ALL and myeloid/lymphoid neoplasm with eosinophilia and gene rearrangements (MLN-EGR) in blast crisis. As currently defined, the diagnosis of MLN-EGR relies on the hematologic presentations and the identification of marker gene fusions (including PCM1-JAK2, ETV6-JAK2, and BCR-JAK2). However, these same gene fusions, when limited to B-lymphoblasts, also define Ph-like B-ALL. Yet, our case does not conform to either condition. Therefore, the assessment for lineage restriction of gene rearrangements to reflect the pathophysiologic difference between B-ALL and MLN-EGR in blast crisis is likely a more robust diagnostic approach and allows the inclusion of MLN-EGR with novel gene fusions.

Background:

Despite smoking being a well-established risk factor for pancreatic cancer, there is a need to further characterize pancreatic cancer risk according to lifespan smoking patterns and other smoking features, such as tobacco type. Our aim was to deeply investigate them within a large European case–control study.

Tobacco smoking is the primary risk factor for lung cancer, driven by the addictive nature of nicotine and the indisputable carcinogenicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as well as other compounds. The integration of lung cancer chemoprevention with smoking cessation is one potential approach to reduce this risk and mitigate lung cancer mortality. Experimental data from our group suggest that kava, commonly consumed in the South Pacific Islands as a beverage to promote relaxation, may reduce lung cancer risk by enhancing NNK detoxification and reducing NNK-derived DNA damage. Building upon these observations, we conducted a pilot clinical trial to evaluate the effects of a 7-day course of kava on NNK metabolism in active smokers. The primary objective was to compare urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL plus its glucuronides, major metabolites of NNK) before and after kava administration as an indicator of NNK detoxification. Secondary objectives included determining kava's safety, its effects on DNA damage, tobacco use, and cortisol (a biomarker of stress). Kava increased urinary excretion of total NNAL and reduced urinary 3-methyladenine in participants, suggestive of its ability to reduce the carcinogenicity of NNK. Kava also reduced urinary total nicotine equivalents, indicative of its potential to facilitate tobacco cessation. Plasma cortisol and urinary total cortisol equivalents were reduced upon kava use, which may contribute to reductions in tobacco use. These results demonstrate the potential of kava intake to reduce lung cancer risk among smokers.

While smoking is inextricably linked to oral/head and neck cancer (HNSCC), only a small fraction of smokers develop HNSCC. Thus, we have sought to identify other factors, which may influence the development of HNSCC in smokers including microbiology. To determine microbial associations with HNSCC among tobacco users, we characterized oral microbiome composition in smokers with and without HNSCC. 16S rRNA MiSeq sequencing was used to examine the oral mucosa microbiome of 27 smokers with (cases) and 24 without HNSCC (controls). In addition, we correlated previously reported levels of DNA damage with the microbiome data. Smokers with HNSCC showed lower microbiome richness compared with controls (q = 0.012). Beta-diversity analyses, assessed as UniFrac (weighted and unweighted) and Bray–Curtis distances, showed significant differences in oral mucosal microbiome signatures between cases and controls (r² = 0.03; P = 0.03) and higher interindividual microbiome heterogeneity in the former (q ≤ 0.01). Higher relative abundance of Stenotrophomonas and Comamonadaceae and predicted bacterial pathways mainly involved in xenobiotic and amine degradation were found in cases compared with controls. The latter, in contrast, exhibited higher abundance of common oral commensals and predicted sugar degradation pathways. Finally, levels of DNA damage in the oral cavity were correlated with the microbiome profiles above. Oral microbiome traits differ in smokers with and without HNSCC, potentially informing the risk of eventual HNSCC and shedding light into possible microbially mediated mechanisms of disease. These findings present data that may be useful in screening efforts for HNSCC among smokers who are unable to quit.

Brain metastases are associated with poor prognosis irrespective of the primary tumor they originate from. Current treatments for brain metastases are palliative, and patients with symptomatic brain metastasis have a one-year survival of <20%. Lung cancer, breast cancer, and melanoma have higher incidences of brain metastases compared with other types of cancers. However, it is not very clear why some cancers metastasize to the brain more frequently than others. Studies thus far suggest that brain-specific tropism of certain types of cancers is defined by a winning combination of the following factors: unique genetic subtypes of primary tumors or its subclones enabling detachment, dissemination, blood–brain barrier penetration, plus proliferation and survival in hypoxic low-glucose microenvironment; specific transcriptomic and epigenetic changes of colony-forming metastatic cells, allowing their outgrowth; favorable metastasis-permissive microenvironment of the brain created by interactions of cancer cells and cells in the brain through triggering inflammation, recruiting myeloid-derived suppressor cells, and promoting metabolic adaptation; immunosuppression resulting in the failure of adaptive immune response to recognize or kill cancer cells in the brain. Here, we briefly review recent advances in understanding brain metastasis organotropism and outline directions for future research.

BACKGROUND AND PURPOSE:

Not all tandem occlusions diagnosed on traditional vascular imaging modalities, such as MRA, represent actual complete ICA occlusion. This study aimed to explore the utility of high-resolution vessel wall imaging in identifying true ICA tandem occlusions and screening patients for their suitability for endovascular recanalization.

BACKGROUND AND PURPOSE:

Flow-diverter treatment for previously stented aneurysms has been reported to be less effective and prone to complications. In this study, we evaluated the effectiveness and safety of flow diverters for recurrent aneurysms after stent-assisted coiling.

BACKGROUND AND PURPOSE:

Flow diversion for the posterior circulation remains a promising treatment option for selected posterior circulation aneurysms. The Flow-Redirection Intraluminal Device (FRED) system has not been previously assessed in a large cohort of patients with posterior circulation aneurysms. The purpose of the present study was to assess safety and efficacy of FRED in this location.

BACKGROUND AND PURPOSE:

After endovascular coiling of intracranial aneurysms, round dark parenchymal lesions believed to be particulate metal are sometimes encountered in MR imaging studies of the brain. We used SWI to assess the frequency of such occurrences, in addition to exploring likely causes and clinical implications.

BACKGROUND AND PURPOSE:

Computed tomography angiography offers a non-invasive alternative to DSA for the assessment of cerebral vasospasm following subarachnoid hemorrhage but there is limited evidence regarding its reliability. Our aim was to perform a systematic review (Part I) and to assess (Part II) the inter- and intraobserver reliability of CTA in the diagnosis of cerebral vasospasm.

According to Deputy Minister of Construction Nguyen Viet Sinh, Vietnam will have at least 3 smart cities in 3 key economic regions: North, Central and South. Thus, by the next 6 years, Hanoi, Da Nang and Ho Chi Minh City will become smart cities.

Normally, you put your property on the market but the estate agent is the one who actually sells it to buyers. It is a critical decision to choose the right agent and protect you from any future trouble. The questions below may help you.

As with other types of investment, real estate investors need a good vision and smart strategies to make it profitable. Here are 6 important guides for investors to avoid loss and gain profit from their real estate investment.

As any good Guardian knows, Destiny 2 isn’t just a jargon-filled sci-fi loot ’em up. It’s just as much, if not more so, a far-future fashion show. But in a game about constantly trading out new gear, keeping a fresh look has always felt a little contentious. This week, Bungie revealed that Year 4 will […]

Robots are being developed to help with tasks like fixing the sea cages where fish are farmed, and their size seems to be all that affects how the fish react

The data centres servicing our beloved digital devices gobble huge amounts of electricity. A new way to think about heat and energy could help us meet growing demand without burning through the world's resources

The UK government has pledged to make smart motorways safer by rolling out a radar detection system within the next three years, but New Scientist can reveal that just 7 per cent of the roads are protected by the measure today

An AI can detect the presence of smells and even distinguish between scents like ammonia or carbon monoxide, which could be useful for detecting hazardous odours

A program that combines artificial intelligence and geometrical modelling can create an accurate 3D model of your face from a single 20-second video

A 3D printed grate can be used to make a smart window that blocks heat from sunlight out in the summer while letting it through in the winter, conserving energy

Not because of public concerns, although there are plenty of those, but because of the pandemic-induced plunge in local real estate.

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

राजस्थान अधीनस्थ और मंत्रिस्तरीय सेवा चयन बोर्ड (RSMSSB), जयपुर ने अपनी आधिकारिक वेबसाइट पर जूनियर इंस्ट्रक्टर और उद्योग विकास के पदों पर हुई भर्ती परीक्षा के के लिए परीक्षा के अंक अपलोड कर दिए हैं।

The Milky Way ate another galaxy called Gaia-Enceladus, and the waves passing through a star have shown us that it happened at most 11.6 billion years ago

A strange supernova that’s 100 times brighter than it should be has long been a mystery, but it may be explained by the explosion slamming into a cloud of gas

When asteroid Armageddon is upon us, we can't just call Bruce Willis. Meet the people who really do watch the skies – and make detailed plans for our survival

Proxima Centauri b, a planet orbiting our nearest stellar neighbour, is being blasted with cosmic rays and solar flares – which could make it warm enough to host life

There is something deeply unsettling about the lionization of Andrew Cuomo and his handling of the epidemic, especially in the light of the raw statistics

Skydio crams all its autonomous magic into a sleek consumer drone that costs under $1k

Self-driving cars and medical robots need an infant’s understanding of physics to succeed

Psychologist Simon Baron-Cohen thinks scientists and engineers could be more likely to have a child with autism. Some researchers say the proof isn't there.

We're back and better* than ever! On this special episode of the RPGCast we do a deeper dive into what we've been playing and discuss our holiday hauls. *Note: RPG Cast 526 may not actually be better than any other previous RPG Cast.

The ‘haunted doll’ look of Donald Trump’s son-in-law has attracted a lot of attention. When people comment on famous women and surgery there is often a backlash, but should the same apply here?

What has happened to Jared Kushner’s face?
Richard, by email

People get a little antsy about the subject of cosmetic surgery: they don’t like to be asked if they have had it, and public speculation over whether someone else has had it is generally considered to be de trop. I don’t really get this. Maybe it’s because I am 100% the world’s worst liar, but pretending to not see that someone’s face has completely changed is a form of magical thinking that is just beyond my capabilities.

Environmental biologists have warned that the potential spread of COVID-19 via sewage 'must not be neglected' in the battle to protect human health.

New research finds that sleep problems in a baby's first 12 months may not only precede an autism diagnosis, but also may be associated with altered growth trajectory in a key part of the brain, the hippocampus.

Desmond Mombeyarara, 34, was with his son when officers shot him with a stun gun

Anti-racism protesters have gathered outside a petrol station in Greater Manchester to demonstrate against the stun gun shooting by police of a black man in the company of his distressed son.

Desmond Mombeyarara, 34, was shot with a stun gun by police on Wednesday evening after officers stopped him for allegedly speeding.

Excellent film-maker that he is, Watiti seems to fit the Marvel blueprint far more easily than he does Star Wars’ more venerable, old-school template

When entertainment reporters play Hollywood roulette, the practice of attaching directors and stars to forthcoming movies based on little more than rumour, their little white balls nearly always seem to land on Taika Waititi’s number. If you’ve been keeping a close eye on this column over the past year, you’ve probably spotted the white-hot Kiwi director being touted for a remake of Flash Gordon and the next Deadpool movie among other projects, neither of which have yet come to fruition.

Waititi’s next film, according to reports this week, will be a Star Wars episode. Will he end up making it to the first day of production on this one? The chances seem better, as Disney has officially confirmed the appointment via the space saga’s official website, with 1917 co-writer Krysty Wilson-Cairns helping deliver a script. But this is Star Wars we are talking about – Colin Trevorrow, Josh Trank, Phil Lord and Christopher Miller, David Benioff and DB Weiss are among the numerous film-makers who have cheerily signed up to try to bring back the glory days of the long-running series in recent times, only to ultimately fall foul of Lucasfilm president Kathleen Kennedy’s merciless Force choke.

Julia Garner excels as a junior assistant to a predatory media mogul boss in Kitty Green’s powerfully understated #MeToo drama

A performance of few words but immense physical eloquence by Julia Garner anchors this impressively chilling #MeToo-era drama about workplace harassment and abuse. Following a day in the life of a young woman with dreams of making her mark in the film and television industry, it’s a sobering portrait of a dirty little secret that was brought into the news spotlight by the Harvey Weinstein scandal. All the more powerful for its understated tone, this low-key piece packs a hefty punch as it exposes the web of silence that enabled a very modern horror story.

Garner (who won an Emmy for her work on TV’s Ozark) is Jane, a high-achieving college graduate who finds herself on the bottom rung of the ladder as a junior assistant to an unnamed entertainment mogul in New York. The appointment may hold promises of great opportunities ahead, but for now it’s fairly soul destroying. An opening sequence, played out to the lonely strains of Tamar-kali’s sparse score, finds Jane being driven to the office before dawn, turning on the lights above her colleagues’ desks – first in, last out. Her tasks are menial yet weirdly demanding: making coffee, changing the paper in the photocopier, ordering lunch, and arranging travel and accommodation for an ever-changing roster of offhand executives and needy clients.