Dynamics of affect modulation in neurodevelopmental disorders (DynAMoND) - study design of a prospective cohort study.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common neuro-developmental disorder that often persists into adulthood. Moreover, it is frequently accompanied by bipolar disorder (BD) as well as borderline personality disorder (BPD). It is unclear whether these disorders share underlying pathomechanisms, given that all three are characterized by alterations in affective states, either long or short-term.

Targeting molecular pathways to control immune checkpoint inhibitor toxicities.

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but are frequently associated with immune-related adverse events (irAEs). This article offers a novel synthesis of findings from both preclinical and clinical studies, focusing on the molecular mechanisms driving irAEs across diverse organ systems. It examines key immune cells, such as T cell subsets and myeloid cells, which are instrumental in irAE pathogenesis, alongside an in-depth analysis of cytokine signaling [interleukin (IL)-6, IL-17, IL-4), interferon γ (IFN-γ), IL-1β, tumor necrosis factor α (TNF-α)], integrin-mediated interactions [integrin subunits αITGA)4 and ITGB7], and microbiome-related factors that contribute to irAE pathology.

Comparative efficacy and safety of treatment regimens for Pneumocystis jirovecii pneumonia in people living with HIV - A systematic review and network meta-analysis of randomized controlled trials.

Background: Pneumocystis jirovecii pneumonia (PCP) is a serious opportunistic infection in people living with HIV (PWH) who have low CD4 counts. Despite its side effects, trimethoprim-sulfamethoxazole (TMP-SMX) is currently considered the primary treatment for PCP.

Objectives: To compare the efficacy (treatment-failure and mortality) and tolerability (treatment change) of PCP treatment-regimens with a frequentist network meta-analysis (NMA).

Isolating high-quality RNA for RNA-Seq from 10-year-old blood samples.

There is much interest in analysing RNA, particularly with RNA Sequencing, across both research and diagnostic domains. However, its inherent instability renders it susceptible to degradation. Given the imperative for RNA integrity in such applications, proper storage and biobanking of blood samples and successful subsequent RNA isolation is essential to guarantee optimal integrity for downstream analyses.

Development of a Sensitive and Reliable Meso Scale Discovery-Based Electrochemiluminescence Immunoassay to Quantify TDP-43 in Human Biofluids.

Transactive response DNA-binding protein of 43 kDa (TDP-43) is a major component of pathological inclusions in various neurodegenerative disorders, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration. The detection of TDP-43 in biofluids is crucial for the development of diagnostic and prognostic indicators of disease and therapeutic development for TDP-43-related proteinopathies. Despite its potential as a biomarker for numerous neurological disorders, the lack of a sensitive and reproducible TDP-43 assay hinders progress in TDP-43-based therapy development, underscoring the need for an effective and standardized method for accurate quantification.

Effectiveness of the BNT162b2 XBB.1.5-adapted vaccine against COVID-19 hospitalization related to the JN.1 variant in Europe: a test-negative case-control study using the id.DRIVE platform.

Background: Prior studies have reported lower effectiveness of XBB.1.5-adapted vaccines against hospitalization related to the Omicron JN.

A Pooled Pharmacokinetic Analysis for Piperacillin/Tazobactam Across Different Patient Populations: From Premature Infants to the Elderly.

Background And Objectives: The pharmacokinetics (PK) of piperacillin/tazobactam (PIP/TAZ) is highly variable across different patient populations and there are controversies regarding non-linear elimination as well as the fraction unbound of PIP (f). This has led to a plethora of subgroup-specific models, increasing the risk of misusing published models when optimising dosing regimens. In this study, we aimed to develop a single model to simultaneously describe the PK of PIP/TAZ in diverse patient populations and evaluate the current dosing recommendations by predicting the PK/pharmacodynamics (PD) target attainment throughout life.

An update on access to novel treatment for metastatic melanoma in Europe - A 2024 survey of the European melanoma registry and the European association of dermato-oncology.

Advances in cancer treatments have significantly improved their effectiveness, yet access to first-line therapies remains limited. A 2017 survey revealed that over 25 % of metastatic melanoma patients in Europe lacked access to recommended therapies. To address this, the European Association of Dermato-Oncology and the European Melanoma Registry conducted a follow-up study on the registration and reimbursement of first-line treatments.

Impact of annotation imperfections and auto-curation for deep learning-based organ-at-risk segmentation.

Background And Purpose: Segmentation imperfections (noise) in radiotherapy organ-at-risk segmentation naturally arise from specialist experience and image quality. Using clinical contours can result in sub-optimal convolutional neural network (CNN) training and performance, but manual curation is costly. We address the impact of simulated and clinical segmentation noise on CNN parotid gland (PG) segmentation performance and provide proof-of-concept for an easily implemented auto-curation countermeasure.

Innovative use of the new pulsed-thulium: YAG laser for ureteroscopic lithotripsy: can the "kidney stone calculator" predict lithotripsy duration?

To assess the accuracy of Kidney Stone Calculator(KSC), a software designed for surgical planning, in predicting the duration of lithotripsy during flexible ureteroscopy(FURS) when using the novel pulsed-Thulium: YAG(p-Tm: YAG) laser. From February to August 2023, a single-center prospective study was conducted, including patients with kidney or ureteral stones through non-contrast computed tomography(NCCT), who underwent FURS with p-Tm: YAG laser lithotripsy. KSC used three-dimensional segmentation of the stones from NCCT images, along with an interactive user interface for laser settings, to estimate the stone volume(SV) and the lithotripsy duration(LD).

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i): Mechanisms of resistance and where to find them.

CDK4/6 inhibitors (CDK4/6i) have significantly impacted on the treatment of HR + HER2 negative (HER2-) metastatic breast cancer (BC) when combined with endocrine therapy. Nonetheless, despite significant research efforts, the mechanisms of de novo and acquired resistance to CDK4/6i have not yet been fully elucidated, highlighting the need for a deeper understanding of these process. Additionally, the importance of dissecting CDK4/6i resistance from endocrine resistance for personalized treatment is increasingly recognized.

Atezolizumab, bevacizumab, pemetrexed and platinum for EGFR-mutant NSCLC patients after EGFR TKI failure: A phase II study with immune cell profile analysis.

Background: Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) remains a significant hurdle for patients with EGFR-mutated non-small cell lung cancer (NSCLC), particularly those lacking the EGFR. IMpower 150 study demonstrated promising efficacy for a combination of immune-chemotherapy and bevacizumab in patients with EGFR-mutated NSCLC.

Methods: This open-label, single-arm, phase II trial evaluated the efficacy and immune cell profile of the modified regimen combining atezolizumab, bevacizumab (7.

The role of artificial intelligence in standardizing global longitudinal strain measurements in echocardiography.

Aims: To evaluate the accuracy and feasibility of artificial intelligence (AI) in left ventricular global longitudinal strain (GLS) analysis as compared to conventional (Manual) and semi-automated (SemiAuto) method in echocardiography (Echo).

Methods And Results: GLS validation was performed on 550 standard Echo exams by expert cardiologists. The performance of a beginner cardiologist without experience of GLS analysis was assessed on a subset of 90 exams.

What is the lower limb length discrepancy after arthroplasty for proximal femoral fracture? A prospective, multicenter observational study of 590 hips.

Introduction: Lower limb length discrepancy (LLD) following hip arthroplasty after proximal femoral fracture (PFFA) is little studied. The aim of this work was to answer the following questions: 1) What are the incidence and mean values ​​of LLD after PFFA? 2) What are the clinical consequences (tolerance) of LLD after PFFA? 3) Can we identify risk factors for LLD after PFFA? 4) Is there a significant difference in terms of LLD after PFFA to treat intra- versus extra-capsular fractures?

Hypothesis: LLD after proximal femoral fracture arthroplasty is rare but has good clinical tolerance, given the low functional demands of the patients.

Patients And Methods: This is a multicenter prospective observational cohort study (15 centers), including 590 patients, operated on for hip arthroplasty for proximal femur fracture between May 2022 and June 2023.

Temporal Trends of Ischemic Stroke Risk in Patients With Incident Atrial Fibrillation Before Anticoagulation.

Background: Atrial fibrillation (AF) is a major risk factor for ischemic stroke (IS), but whether the magnitude of this risk has changed over time is unknown.

Objectives: This study sought to investigate temporal trends in IS rates in patients with incident AF before oral anticoagulant agent (OAC) therapy.

Methods: The nationwide FinACAF (Finnish Anticoagulation in Atrial Fibrillation) study covers patients with AF at all levels of care in Finland from 2007 to 2018.

Prognostic Biomarkers in Evolving Melanoma Immunotherapy.

Melanoma, a highly aggressive form of skin cancer, has seen significant advancements in treatment through the introduction of immunotherapy. However, the variability in patient responses underscores the need for reliable biomarkers to guide treatment decisions. This article reviews key biomarkers in melanoma immunotherapy, such as PD-L1 expression, tumor mutational burden (TMB), and gene expression profiles (GEPs).

Efficacy of CTLA-4 checkpoint therapy is dependent on IL-21 signaling to mediate cytotoxic reprogramming of PD-1CD8 T cells.

The mechanisms underlying the efficacy of anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) therapy are incompletely understood. Here, by immune profiling responding PD-1CD8 T (T) cell populations from patients with advanced melanoma, we identified differential programming of T cells in response to combination therapy, from an exhausted toward a more cytotoxic effector program. This effect does not occur with anti-PD-1 monotherapy.

Degradable starch microspheres transarterial chemoembolization (DSM-TACE) in patients with unresectable hepatocellular carcinoma: results from the Prospective Multicenter Observational HepaStar Trial.

Objectives: Despite increasing interest, prospective data on the use of degradable starch microsphere-transarterial chemoembolization (DSM-TACE) in the management of patients with unresectable HCC are still scarce. The objective of the HepaStar study was to collect prospective safety and effectiveness data in a prospective multicenter observational study.

Materials And Methods: Between January 2017 and December 2022, consecutive participants with unresectable or recurrent HCC treated with DSM-TACE as standard of care at 6 participating centers in Europe were enrolled.

Evaluation of S100A8/A9 and neutrophils as prognostic markers in metastatic melanoma patients under immune-checkpoint inhibition.

Immune-checkpoint inhibitors (ICIs) have revolutionized melanoma treatment, yet approximately half of patients do not respond to these therapies. Identifying prognostic biomarkers is crucial for treatment decisions. Our retrospective study assessed liquid biopsies and tumor tissue analyses for two potential biomarkers: danger-associated molecular pattern (DAMP) S100A8/A9 and its source, neutrophils.

Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancer.

High-risk non-muscle-invasive bladder cancer (NMIBC) presents high recurrence and progression rates. Despite the use of Bacillus Calmette-Guérin gold-standard immunotherapy and the recent irruption of anti-PD-1/PD-L1 drugs, we are missing a comprehensive understanding of the tumor microenvironment (TME) that may help us find biomarkers associated to treatment outcome. Here, we prospectively analyzed TME composition and PD-L1 expression of tumor and non-tumoral tissue biopsies from 73 NMIBC patients and used scRNA-seq, transcriptomic cohorts and tissue micro-array to validate the prognostic value of cell types of interest.

Sex differences in patients with Non-Small Cell Lung Cancer harboring driver fusions treated with tyrosine kinase inhibitors: a systematic review.

Background: While targeted therapies have transformed the treatment landscape of oncogene-addicted non-small cell lung cancer (NSCLC), the influence of sex on treatment outcomes remains insufficiently understood.

Objectives: This systematic review aimed to investigate the impact of sex on clinical outcomes in patients with NSCLC harboring driver fusions treated with targeted therapies enrolled in clinical trials.

Data Sources And Methods: A comprehensive literature search was conducted using PubMed, Embase, and relevant conference abstracts to identify phase III randomized and early clinical trials that reported sex-specific data, including progression-free survival (PFS), overall survival (OS), overall response rate, and adverse events (AEs), in patients with fusion-positive NSCLC treated with tyrosine kinase inhibitors (TKIs).