Apoptotic priming in senescence predicts specific senolysis by quantitative analysis of mitochondrial dependencies.

Cellular senescence contributes to a variety of pathologies associated with aging and is implicated as a cellular state in which cancer cells can survive treatment. Reported senolytic drug treatments act through varying molecular mechanisms, but heterogeneous efficacy across the diverse contexts of cellular senescence indicates a need for predictive biomarkers of senolytic activity. Using multi-parametric analyses of commonly reported molecular features of the senescent phenotype, we assayed a variety of models, including malignant and nonmalignant cells, using several triggers of senescence induction and found little univariate predictive power of these traditional senescence markers to identify senolytic drug sensitivity.

Artificial intelligence for hemodynamic monitoring with a wearable electrocardiogram monitor.

Background: The ability to non-invasively measure left atrial pressure would facilitate the identification of patients at risk of pulmonary congestion and guide proactive heart failure care. Wearable cardiac monitors, which record single-lead electrocardiogram data, provide information that can be leveraged to infer left atrial pressures.

Methods: We developed a deep neural network using single-lead electrocardiogram data to determine when the left atrial pressure is elevated.

Endogenous thymic regeneration: restoring T cell production following injury.

Despite its importance for generating and maintaining a healthy and broad T cell repertoire, the thymus is exquisitely sensitive to acute damage. Marked thymic involution occurs in response to stimuli as diverse as infection, stress, pregnancy, malnutrition, drug use and cytoreductive chemotherapy. However, the thymus also has a remarkable capacity for repair, although this regenerative capacity declines with age.

Prostate MRI and clinicopathologic risk calculator to predict laterality of extraprostatic extension at radical prostatectomy.

Background: Traditional nomograms can inform the presence of extraprostatic extension (EPE) but not laterality, which remains important for surgical planning, and have not fully incorporated multiparametric MRI data. We evaluated predictors of side-specific EPE on surgical pathology including MRI characteristics and developed side-specific EPE risk calculators.

Methods: This was a retrospective cohort of patients evaluated with mpMRI prior to radical prostatectomy (RP) in our eleven hospital healthcare system from July 2018-November 2022.

Effect of DLPFC rTMS on anhedonia and alpha asymmetry in depressed patients.

Anhedonia, a core symptom of depression, has been defined as the loss of pleasure or lack of reactivity to pleasurable stimuli. Considering the relevance of alpha asymmetry to MDD and anhedonia, we explored the effect of dorsolateral prefrontal cortex (DLPFC) stimulation on frontal and posterior EEG alpha asymmetry (FAA and PAA, respectively), in this exploratory investigation. 61 participants randomly received sham (n = 11), bilateral (BS; n = 25), or unilateral stimulation (US; n = 25) of the DLPFC.

Peer-Led Adjunctive Interventions for Increasing the Reach of HIV Prevention and Care Interventions to Latino/x/e Men Who Have Sex with Men: a Scoping Review.

Purpose Of Review: Latino/x/e men who have sex with men (LMSM) in the United States are disproportionately affected by HIV. Peer-led adjunctive interventions show promise for enhancing engagement in HIV prevention and care among LMSM, but their effectiveness and implementation remain underexplored. This scoping review aimed to map existing evidence on peer-led interventions, identify gaps, and inform future research for enhancing HIV prevention and care among LMSM.

The effects of war-related experiences on mental health symptoms of individuals living in conflict zones: a longitudinal study.

On October 7, 2023, a large-scale attack in southern Israel and the subsequent war resulted in extensive loss of life and injuries, with many individuals experiencing traumatic losses, such as family members or close friends being killed or kidnapped. This study aims to longitudinally examine its effects on mental health, specifically, clinical symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD). We anticipated greater symptom severity among individuals who experienced traumatic loss, were forcibly displaced, or suffered income loss, as well as among women and members of ethnic minorities.

Causal genes identification of giant cell arteritis in CD4+ Memory t cells: an integration of multi-omics and expression quantitative trait locus analysis.

Background: Giant cell arteritis (GCA) is a prevalent artery and is strongly correlated with age. The role of CD4+ Memory T cells in giant cell arteritis has not been elucidated.

Method: Through single-cell analysis, we focused on the CD4+ Memory T cells in giant cell arteritis.

Knockout or inhibition of DHPS suppresses ovarian tumor growth and metastasis by attenuating the TGFβ pathway.

Deoxyhypusine synthase (DHPS) is an enzyme encoded by the DHPS gene, with high expression in various cancers, including ovarian cancer (OC). DHPS regulates the translation initiation factor EIF5A, and EIF5A2 knockout inhibits OC tumor growth and metastasis by blocking the epithelial-to-mesenchymal transition (EMT) and the TGFβ pathway. In this study, we show that DHPS is amplified in OC patients, and its elevated expression correlates with poor survival.

Prediction of checkpoint inhibitor immunotherapy efficacy for cancer using routine blood tests and clinical data.

Predicting whether a patient with cancer will benefit from immune checkpoint inhibitors (ICIs) without resorting to advanced genomic or immunologic assays is an important clinical need. To address this, we developed and evaluated SCORPIO, a machine learning system that utilizes routine blood tests (complete blood count and comprehensive metabolic profile) alongside clinical characteristics from 9,745 ICI-treated patients across 21 cancer types. SCORPIO was trained on data from 1,628 patients across 17 cancer types from Memorial Sloan Kettering Cancer Center.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial.

The MEK inhibitor selumetinib induces objective responses and provides clinical benefit in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). To evaluate whether similar outcomes were possible in adult patients, in whom PN growth is generally slower than in pediatric patients, we conducted an open-label phase 2 study of selumetinib in adults with NF1 PNs. The study was designed to evaluate objective response rate (primary objective), tumor volumetric responses, patient-reported outcomes and pharmacodynamic effects in PN biopsies.

Ferric carboxymaltose for anemia in late pregnancy: a randomized controlled trial.

Over 46% of African pregnant women are anemic. Oral iron is recommended but often suboptimal, particularly late in pregnancy. Intravenous ferric carboxymaltose (FCM) could treat anemia in women in the third trimester in sub-Saharan Africa.

Glecirasib in KRAS-mutated nonsmall-cell lung cancer: a phase 2b trial.

Glecirasib (JAB-21822) is a new covalent oral KRAS-G12C inhibitor. This multicenter, single-arm phase 2b study assessed the efficacy and safety of glecirasib administered orally at 800 mg daily in patients with locally advanced or metastatic KRAS-mutated nonsmall-cell lung cancer. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC).

Excess mortality due to COVID-19 in Thailand between the pandemic and post-pandemic periods.

The coronavirus disease 2019 (COVID-19) pandemic had a significant effect on mortality rates worldwide, with Thailand being no exception. Gaining insights into the impact of pandemic-related mortality is essential for assessing its broader consequences on public health. This study aimed to analyze excess deaths during the pandemic (January 1, 2020-September 30, 2022) and post-pandemic period (October 2022-December 2023) at regional and national levels in Thailand.

Use of inpatient palliative care in metastatic testicular cancer patients undergoing critical care therapy: insights from the national inpatient sample.

To test for rates of inpatient palliative care (IPC) in metastatic testicular cancer patients receiving critical care therapy (CCT). Within the Nationwide Inpatient Sample (NIS) database (2008-2019), we tabulated IPC rates in metastatic testicular cancer patients receiving CCT, namely invasive mechanical ventilation (IMV), percutaneous endoscopic gastrostomy tube (PEG), dialysis for acute kidney failure (AKF), total parenteral nutrition (TPN) or tracheostomy. Univariable and multivariable logistic regression models addressing IPC were fitted.

Patients with dementia with Lewy bodies display a signature alteration of their cognitive connectome.

Cognition plays a central role in the diagnosis and characterization of dementia with Lewy bodies (DLB). However, the complex associations among cognitive deficits in different domains in DLB are largely unknown. To characterize these associations, we investigated and compared the cognitive connectome of DLB patients, healthy controls (HC), and Alzheimer's disease patients (AD).

The association between the healthy lifestyle index and MRI-derived body composition measurements in the UK Biobank study.

A high healthy lifestyle index (HLI) score, which reflects an adequate amount of sleep, no alcohol consumption, no smoking, a moderate to high physical activity level, a high quality diet, and a normal body mass index (BMI), has been associated with reduced risk of morbidity and mortality. We examined the relationship between the HLI and measurements of adipose and lean tissue volumes measured using magnetic resonance imaging (MRI). We studied 33,002 participants in the UK Biobank study, aged 40-69 years at enrolment.

Umbrella review of social inequality in digital interventions targeting dietary and physical activity behaviors.

Digital interventions are increasingly utilized as a lever to promote population health, yet not everyone may equally benefit from them. This umbrella review pooled the insights from available systematic and scoping reviews regarding potential social inequalities in digital intervention uptake, engagement and effectiveness, focusing on the promotion of weight-related behaviors (diet, physical activity, sedentary behavior) and weight loss (maintenance) in adults. Six databases were searched from 1970 to October 2023.

SMYD3 drives cell cycle and epithelial-mesenchymal transition pathways through dual gene transcriptional repression and activation in HPV-negative head and neck cancer.

Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type in the world and is associated with an overall poor prognosis. The protein methyltransferase SET and MYND domain-containing 3 (SMYD3), which trimethylates H3K4, activates gene transcription and enhances several oncogenic pathways, including epithelial-mesenchymal transition and cell cycle related pathways, in various cancer types. It was also recently shown that SMYD3 is overexpressed in HPV-negative HNSCC, and represses the expression of type I IFN response genes, contributing to resistance to anti-PD-1 checkpoint blockade in this disease.

Two-year follow-up of gait and postural control following initiation of recombinant human tripeptidyl intracerebroventricular enzyme replacement therapy in two atypical CLN2 patients.

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disorder leading to premature mortality. Ambulatory CLN2 patients typically receive standard of care treatment through biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) involving recombinant human tripeptidyl peptidase 1, known as cerliponase alfa (Brineura, Biomarin Pharmaceuticals). This study longitudinally assessed the impact of ICV cerliponase alfa ERT on gait, and postural control across a two-year span in two siblings diagnosed with atypical CLN2 disease.