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Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials

In three RCTs, Tirzepatide was associated with clinically meaningful weight loss among adults with overweight or obesity, even when concomitant weight-inducing medications were initiated during treatment.

Question What is the association between tirzepatide and weight reduction among patients with overweight or obesity who initiated concomitant weight-inducing medications?

Findings In this post hoc analysis of participants in the SURMOUNT-1,-3, and-4 trials receiving at least 1 concomitant weight-inducing medication (17.3%-20.0%), tirzepatide treatment was associated with comparable weight loss to the primary study results.

Triple pre-surgery therapy may boost immunity against soft tissue sarcoma

Early results from preclinical studies and a clinical trial led by researchers at the UCLA Health Jonsson Comprehensive Cancer Center and Stanford Medicine suggest that combining targeted radiation therapy with an experimental immune-boosting drug called BO-112 and anti-PD-1 therapy before surgery may help the immune system fight aggressive soft tissue sarcomas.

The findings, published in Cancer Discovery, show that the approach can reshape the tumor microenvironment to activate the body’s immune cells against cancer.

Soft tissue sarcomas are a rare and often hard-to-treat group of cancers that typically require a combination of surgery, radiation therapy and other systemic treatments. However, these tumors may still be resistant to standard therapies, highlighting the need for new treatment strategies.

Unraveling the secrets of telomerase, an enzyme linked to aging and cancer

A central question in molecular biology is how cells protect their chromosomes from damage during repeated cell division. At the heart of this protective process is an enzyme called telomerase. Now an international research team has mapped the three-dimensional structure of telomerase in the yeast Saccharomyces cerevisiae, a widely used model organism in genetics.

Using cutting-edge technology, the scientists were able to visualize the architecture of this complex enzyme in unprecedented detail, uncovering unexpected features that may explain how it functions.

This major discovery was the result of an international collaboration between Pascal Chartrand, a professor in the Department of Biochemistry and Molecular Medicine at Université de Montréal, and researchers from Université de Sherbrooke and the MRC Laboratory of Molecular Biology in the U.K. Their findings were recently published in Science.

X-ray lasers enable the discovery of a critical point in water

Using X-ray lasers, researchers at Stockholm University have been able to determine the existence of a critical point in supercooled water at around −63 °C and 1,000 atmospheres. Ordinary water at higher temperatures and lower pressures is strongly affected by the presence of this critical point, causing the origin of its strange properties. The findings are published in the journal Science.

Water, both omnipresent and essential for life on Earth, behaves very strangely in comparison with other substances. How water’s density, specific heat, viscosity and compressibility respond to changes in pressure and temperature is the complete opposite of other liquids that we know.

All matter shrinks when it is cooled, resulting in an increase in its density. One would therefore expect that water would have a high density at the freezing point. However, looking at a glass of ice water, everything is upside down, since—as we all know—ice cubes float. Strangely enough for the liquid state, water is the densest at 4 degrees C, and therefore it stays on the bottom whether it’s in a glass or in an ocean.

Individual-Level Factors Associated With 10-Year Incidence of Alzheimer Disease and Related Dementias in the VA Million Veteran Program

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IPSC-induced multilineage liver organoids, small intestinal organoids and brain organoids sustain pangenotype hepatitis E virus propagation

Liu et al. present via https://bit.ly/4bV6X0s (Original research, Hepatology section).

A major step forward for translational research, this study shows that human organoid systems can support replication of multiple hepatitis E virus genotypes—offering a powerful new platform for studying infection and testing therapies.

Background Hepatitis E virus (HEV), the leading global cause of acute viral hepatitis, lacks robust in vitro models for virology and pathogenesis research.

Objective We evaluated induced pluripotent stem cell (iPSC)-induced human liver, intestinal and brain organoids (hLOs, hIOs and hBOs) as platforms for HEV infection and replication.

Methods Multilineage organoids were infected with clinical HEV genotypes 1, 3 and 4. Viral tropism, host responses and antiviral efficacy were assessed.

Results All organoids supported the complete life cycle of HEV. hLOs exhibited infection in hepatocytes, cholangiocytes, macrophages and stellate cells, accompanied by elevated interleukin-6 levels, impaired hepatic function (reduced secretion of albumin and Factor IX) and increased levels of alanine aminotransferase and aspartate aminotransferase, indicating hepatocellular injury.

Continue reading “IPSC-induced multilineage liver organoids, small intestinal organoids and brain organoids sustain pangenotype hepatitis E virus propagation” | >

Fluid restriction in patients with heart failure: a systematic review

Background Fluid restriction is a commonly prescribed non-pharmacological intervention in the management of heart failure (HF). However, data on its efficacy and safety are scarce. Recent randomised clinical trial (RCT) data prompt reassessment of the available evidence.

Methods CINAHL, EMBASE, PubMed and the Cochrane Library were searched up to 1 May 2025. RCTs were included if adults with HF were randomised to fluid restriction in comparison to a liberal or unrestricted intake, less strict restriction or usual care. Outcomes of interest were mortality, HF hospitalisation, quality of life (QoL), thirst distress, New York Heart Association (NYHA) class and N-terminal pro-Brain Natriuretic Peptide (CRD42022292319). No meta-analysis was performed due to high heterogeneity of the included trials.

Results In total, four RCTs were included, comprising 682 randomised inpatient, recently discharged and stable outpatient patients (ranging from 46 to 504 patients per trial). Only one study had a low risk of bias. None of the four trials found a significant difference in mortality or HF hospitalisations. For QoL, the results are contradictory, but overall, there is no clear benefit for fluid restriction, but it resulted in more thirst distress. No significant differences in NYHA class or (NT-pro)BNP were observed.

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