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Nivolumab and Ipilimumab Combination Treatment in Advanced dMMR/MSI-H Noncolorectal Cancers

In a nonrandomized phase 2 trial of adults with advanced dMMR/MSI-H noncolorectal cancers, combined nivolumab/ipilimumab showed an objective response rate of 63% and 6-month progression-free survival rate of 71%.

Main Outcomes and Measures The co-primary end points were objective response rate (ORR) and 6-month progression-free survival (6-PFS) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, with the secondary end points being median overall survival (mOS), progression-free survival (PFS), and treatment-related toxic effects.

Results Overall, 52 participants were included. The median (range) age of participants was 62 (29−84) years; 41 (79%) were female individuals and 11 (21%) were male individuals. Overall, 52 patients representing 17 tumor types were enrolled, with the most common tumor type being endometrial cancer (26 [50%]). Twenty-seven patients (52%) were pretreated for metastatic disease. ORR was 63% (95% CI, 50% to 75%) with the median duration of response not being reached and 79% of responses being ongoing. The median PFS and OS have not been reached and the 6-month PFS was 71% (95% CI, 57%-81%). Overall, 12 patients (23%) experienced a grade 3/4 immune-related adverse event.

Conclusions and Relevance This nonrandomized clinical trial found that combined anti–PD-1/CTLA-4 blockade was associated with a high rate of durable responses in dMMR/MSI-H noncolorectal cancers, comparing favorably to published trials using anti–PD-1/programmed cell death ligand 1 monotherapy. Anti–PD-1/CTLA-4 blockade using nivolumab and ipilimumab may represent an alternative treatment option to monotherapy in this patient population.

Scientists Preparing to Simulate Human Brain on Supercomputer

Despite its diminutive size, the organ packs almost 500 feet of wiring and 54.5 million synapses into the size of a grain of sand — an astonishing feat of computational neurology research that allows scientists to better understand how signals travel throughout the brain.

And thanks to significant advances of some of the world’s most capable supercomputers, researchers at the Jülich Research Centre in Germany are now aiming their sights at a far more ambitious goal: a simulation at the scale of the entire human brain.

Previous attempts, dating back a decade, like the Human Brain Project, fell largely flat, despite considerable government funding. But as New Scientist reports, the Jülich researchers think they can push things forward. The idea is to bring together several models of smaller regions of the brain with a supercomputer to run simulations of billions of firing neurons.

Blood Pressure Trajectory in Children From Birth Through Childhood

Higher blood pressure at birth and childhood was associated with a higher risk of hypertension later in life in this ENVIRONAGE study, which tracked BP from birth through childhood.

Question Is blood pressure (BP) at birth and in early childhood associated with BP in later childhood?

Findings In this cohort study of 500 children with BP measured at birth, preschool age (4−6 years), and school age (9−11 years), BP tracked over time. The risk of elevated BP and hypertension at preschool age and school age was associated with BP levels at birth and early childhood.

Inflammation without a LAIR to hide in…

Jacqueline E. Payton & team show loss of LAIR1 results in inflammation-mediated tissue damage and immune defects, leading to S. aureus susceptibility observed in cutaneous T-cell Lymphoma:

The figure shows LAIR1 is protective in S. aureus skin infection in mice.

Address correspondence to: Jacqueline E. Payton, Washington University Department of Pathology and Immunology, 660 S. Euclid Ave., Box 8,118, St. Louis, Missouri 63,110, USA. Phone: 314.362.5935; Email: [email protected].

How scientists are turning thyme into precision medicine

Thyme extract is packed with health-promoting compounds, but it is difficult to control and easy to waste. Researchers created a new technique that traps tiny amounts of the extract inside microscopic capsules, preventing evaporation and irritation. The method delivers consistent nanodoses and could eventually be used in medicines or food products. It may also work for many other natural extracts.

Steam updates AI disclosure form to specify that it’s focused on AI-generated content that is ‘consumed by players,’ not efficiency tools used behind the scenes

The tweak addresses the fact that generative AI tools have been stuffed into just about every piece of software professionals use.

Former Twitter co-founder launches messaging app run on Bluetooth

Jack Dorsey, the co-founder of Twitter, launched BitChat over the weekend as a beta messaging app that works over Bluetooth networks rather than WiFi or mobile data.

Twitter co-founder and former CEO Jack Dorsey has launched a decentralised messaging app to take on WhatsApp and make communication possible without internet access.

Dorsey, who stepped down as CEO in 2021, wrote on social media that he had launched BitChat, a messaging network that works over Bluetooth networks, for beta testing over the weekend.

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