Tumor acidosis-induced DNA damage response and tetraploidy enhance sensitivity to ATM and ATR inhibitors.

Tumor acidosis is associated with increased invasiveness and drug resistance. Here, we take an unbiased approach to identify vulnerabilities of acid-exposed cancer cells by combining pH-dependent flow cytometry cell sorting from 3D colorectal tumor spheroids and transcriptomic profiling. Besides metabolic rewiring, we identify an increase in tetraploid cell frequency and DNA damage response as consistent hallmarks of acid-exposed cancer cells, supported by the activation of ATM and ATR signaling pathways.

Conditioned pain modulation, kinesiophobia, and pain catastrophizing as prognostic factors for chronicity in a population with acute low back pain: An exploratory prospective study.

Background: Psychosocial factors and alteration of the somatosensory functions have been associated with persistent low back pain (LBP). A decreased capacity of the central nervous system to modulate pain has been suggested as a potential contributor to the persistence of pain.

Objective: To investigate whether conditioned pain modulation (CPM), initial symptoms/disability, kinesiophobia, and pain catastrophizing is associated with the transition from acute to chronic LBP.

Time trend in surgical indications and outcomes in ulcerative colitis-A two decades in-depth retrospective analysis.

Background: Recent data regarding the impact of biologics and new surgical techniques on the indications and outcomes of colectomy for ulcerative colitis (UC) are limited.

Aims: The present study aimed at determining the trend of colectomy in UC by comparing colectomy indications and outcomes between 2000 and 2010 and 2011-2020.

Methods: This observational retrospective study was conducted in two tertiary hospitals, including consecutive patients who underwent colectomy between 2000 and 2020.

Association Between Falls and Brain Subvolumes: Results from a Cross-Sectional Analysis in Healthy Older Adults.

Falls are a consequence of gait instability. Cortical and subcortical abnormalities have been associated with gait instability but not yet with falls. This study aims to compare the global and regional brain subvolumes between healthy older fallers and non-fallers.

Anti-Dementia Drugs, Gait Performance and Mental Imagery of Gait: A Non-Randomized Open-Label Trial.

Background: Few studies have examined the effect of anti-dementia drugs (i.e., acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists) on gait performance.

HER2-targeted liposomal doxorubicin displays enhanced anti-tumorigenic effects without associated cardiotoxicity.

Anthracycline-based regimens are a mainstay of early breast cancer therapy, however their use is limited by cardiac toxicity. The potential for cardiotoxicity is a major consideration in the design and development of combinatorial therapies incorporating anthracyclines and agents that target the HER2-mediated signaling pathway, such as trastuzumab. In this regard, HER2-targeted liposomal doxorubicin was developed to provide clinical benefit by both reducing the cardiotoxicity observed with anthracyclines and enhancing the therapeutic potential of HER2-based therapies that are currently available for HER2-overexpressing cancers.