On the use of the healthy lifestyle index to investigate specific disease outcomes.

The healthy lifestyle index (HLI), defined as the unweighted sum of individual lifestyle components, was used to investigate the combined role of lifestyle factors on health-related outcomes. We introduced weighted outcome-specific versions of the HLI, where individual lifestyle components were weighted according to their associations with disease outcomes. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the association between the standard and the outcome-specific HLIs and the risk of T2D, CVD, cancer, and all-cause premature mortality.

Polypharmacology prediction: the long road toward comprehensively anticipating small-molecule selectivity to de-risk drug discovery.

Introduction: Small molecules often bind to multiple targets, a behavior termed polypharmacology. Anticipating polypharmacology is essential for drug discovery since unknown off-targets can modulate safety and efficacy - profoundly affecting drug discovery success. Unfortunately, experimental methods to assess selectivity present significant limitations and drugs still fail in the clinic due to unanticipated off-targets.

Influence of Schneiderian Membrane Perforation on Implant Survival Rate: Systematic Review and Meta-Analysis.

: Maxillary sinus lift is a well-documented and accepted technique in the rehabilitation of the posterior maxilla. Schneiderian membrane perforation is the most common complication and may occur in between 7% and 56% of cases. Different materials and techniques have been described to achieve reparation of the perforation.

Patritumab deruxtecan in HER2-negative breast cancer: part B results of the window-of-opportunity SOLTI-1805 TOT-HER3 trial and biological determinants of early response.

Patritumab deruxtecan (HER3-DXd) exhibits promising efficacy in breast cancer, with its activity not directly correlated to baseline ERBB3/HER3 levels. This research investigates the genetic factors affecting HER3-DXd's response in women with early-stage hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer. In the SOLTI-1805 TOT-HER3 trial, a single HER3-DXd dose was administered to 98 patients across two parts: 78 patients received 6.

PRRX1 silencing is required for metastatic outgrowth in melanoma and is an independent prognostic of reduced survival in patients.

Paired related homeobox 1 (PRRX1) is an inducer of epithelial-to-mesenchymal transition (EMT) in different types of cancer cells. We detected low PRRX1 expression in nevus but increased levels in primary human melanoma and cell lines carrying the BRAF mutation. High expression of PRRX1 correlates with invasiveness and enrichment of genes belonging to the EMT programme.

Association between blood-brain barrier permeability and changes in pulse wave velocity following a recent small subcortical infarct.

Cerebral small vessel disease (cSVD) is associated with increased blood-brain barrier (BBB) permeability. We sought to evaluate whether arterial stiffness might be associated with BBB permeability in patients with cSVD. We assessed BBB permeability using Dynamic Contrast-Enhanced MRI (DCE-MRI) in 29 patients that had suffered a recent small subcortical infarct (RSSI).

The HepHIV 2023 Madrid conference: A call to action for political leadership in reaching the sustainable development goals on earlier testing and linkage to care for HIV, viral hepatitis, and sexually transmitted infections.

Introduction And Objectives: The HepHIV 2023 Conference, held in Madrid in November 2023, highlighted how Europe is not on track to meet the United Nations (UN) sustainable development goals and Joint UN Programme on HIV/AIDS (UNAIDS) targets. This article presents the outcomes of the conference, which focus on ways to improve testing and linkage to care for HIV, viral hepatitis, and other sexually transmitted infections. HIV-related stigma and discrimination, a major barrier to progress, was a key concept of the conference and on the agenda of the Spanish Presidency of the European Union.

Cancer cell plasticity defines response to immunotherapy in cutaneous squamous cell carcinoma.

Immune checkpoint blockade (ICB) approaches have changed the therapeutic landscape for many tumor types. However, half of cutaneous squamous cell carcinoma (cSCC) patients remain unresponsive or develop resistance. Here, we show that, during cSCC progression in male mice, cancer cells acquire epithelial/mesenchymal plasticity and change their immune checkpoint (IC) ligand profile according to their features, dictating the IC pathways involved in immune evasion.

Differences in tumor-associated T-cell receptor repertoires between early-onset and average-onset colorectal cancer.

The incidence of colorectal cancer (CRC) among individuals younger than age 50 (early-onset CRC [EOCRC]) has substantially increased, and yet the etiology and molecular mechanisms underlying this alarming rise remain unclear. We compared tumor-associated T-cell repertoires between EOCRC and average-onset CRC (AOCRC) to uncover potentially unique immune microenvironment-related features by age of onset. Our discovery cohort included 242 patients who underwent surgical resection at Cleveland Clinic from 2000 to 2020.

Proof of Concept Study: Comparability of Microbiome Diversity in Self- and Physician-Collected HPV-Positive and HPV-Negative Cervicovaginal Samples.

Recent studies have revealed the impact of human papillomavirus (HPV) infections on the cervicovaginal microbiome; however, few have explored the utility of self-collected specimens (SCS) for microbiome detection, obtained using standardised methods for HPV testing. Here, we present a proof-of-concept analysis utilising Oxford Nanopore sequencing of the 16S rRNA gene in paired samples collected either by the patient using an Evalyn Brush or collected by a physician using liquid-based cytology (LBC). We found no significant differences in the α-diversity estimates between the SCS and LBC samples.

Rituximab in the treatment of progressive interstitial lung disease associated with the antisynthetase syndrome.

Objective: To assess the real-world, long-term effectiveness of rituximab (RTX) as a rescue therapy in patients with antisynthetase syndrome and progressive interstitial lung disease (ASS-ILD).

Methods: Multicentre observational retrospective longitudinal study of a cohort of patients with ASS-ILD that started treatment with RTX due to recurrent or ongoing progressive ILD despite therapy with glucocorticoids and immunosuppressants.

Results: Twenty-eight patients were analyzed.

Increase of pertussis cases in the Vallès region, Catalonia, Spain, September 2023 to April 2024.

We describe a pertussis outbreak in the Vallès region of Catalonia, from September 2023 to April 2024. Incidence was high in children aged 10-14 years compared with previous outbreaks. Limited impact in newborns could be explained by the high vaccination coverage during pregnancy and at 11 months of age in 2022, at 85% and 94.

The hepatocyte epidermal growth factor receptor (EGFR) pathway regulates the cellular interactome within the liver fibrotic niche.

Liver fibrosis is the consequence of chronic liver injury in the presence of an inflammatory component. Although the main executors of this activation are known, the mechanisms that lead to the inflammatory process that mediates the production of pro-fibrotic factors are not well characterized. Epidermal growth factor receptor (EGFR) signaling in hepatocytes is essential for the regenerative processes of the liver; however, its potential role in regulating the fibrotic niche is not yet clear.

KRAS-mutant non-small cell lung cancer (NSCLC) therapy based on tepotinib and omeprazole combination.

Background: KRAS-mutant non-small cell lung cancer (NSCLC) shows a relatively low response rate to chemotherapy, immunotherapy and KRAS-G12C selective inhibitors, leading to short median progression-free survival, and overall survival. The MET receptor tyrosine kinase (c-MET), the cognate receptor of hepatocyte growth factor (HGF), was reported to be overexpressed in KRAS-mutant lung cancer cells leading to tumor-growth in anchorage-independent conditions.

Methods: Cell viability assay and synergy analysis were carried out in native, sotorasib and trametinib-resistant KRAS-mutant NSCLC cell lines.

Clinical considerations when switching antiretroviral therapy.

Introduction: Antiretroviral therapy (ART) can be personalized through simple formulations with high resistance barriers, favorable safety profiles, and novel administration routes. Switching treatments has become a key clinical strategy for addressing drug toxicity and interactions and enhancing adherence and convenience. This strategy aims to improve the quality of life and long-term efficacy, even in challenging cases like people living with HIV (PLWH) with multiple comorbidities, prior virological failure, and drug resistance.

Severe Gastrointestinal Cytomegalovirus Infection in a Patient Diagnosed with Late Onset Combined Immunodeficiency.

Unlabelled: Late onset combined immunodeficiency (LOCID) is a rare variant of common variable immunodeficiency (CVID), typically affecting adult patients who present with opportunistic infections (OI) and/or low CD4+ T lymphocytes. Diagnostic delay is common due to the rareness of this entity, increasing morbidity and mortality. We report on a 66-year-old male who developed a severe gastrointestinal cytomegalovirus (CMV) infection, refractory to antiviral treatment and anti-cytomegalovirus specific human immunoglobulin administration, with a fatal outcome due to an undiagnosed LOCID.

Anticipatory and consummatory neural correlates of monetary and music rewarding stimuli.

Most of the literature on the neural bases of human reward and punishment processing has used monetary gains and losses, but less is known about the neurophysiological mechanisms underlying the anticipation and consumption of other types of rewarding stimuli. In the present study, EEG was recorded from 19 participants who completed a modified version of the Monetary Incentive Delay (MID) task. During the task, cues providing information about potential future outcomes were presented to the participants.

Efficacy and cost-effectiveness of a digital guided self-management intervention to support transition from intensive care to community care in anorexia nervosa (TRIANGLE): pragmatic multicentre randomised controlled trial and economic evaluation.

Background: There is uncertainty regarding how best to support patients with anorexia nervosa following inpatient or day care treatment. This study evaluated the impact of augmenting intensive treatment with a digital, guided, self-management intervention (ECHOMANTRA) for patients with anorexia nervosa and their carers.

Methods: In this pragmatic multicentre randomised controlled trial and economic evaluation, patients with a diagnosis of anorexia nervosa or atypical anorexia nervosa, aged 16+ and attending one of the 31 inpatient or day-patient services in the UK were randomised with one of their carers to receive ECHOMANTRA plus treatment as usual (TAU), or TAU alone.