Curative-Intended Management of Synchronous Esophageal and Rectal Cancer-A Systematic Literature Review.

Purpose: Synchronous esophageal (EC) and rectal carcinoma (RC) is a rare and challenging condition, particularly in curative-intended treatment. Especially locally advanced tumors may not be suitable for primary resection and require individual multimodal treatment. This review examines curative-intended management of synchronous EC and RC.

Validation of a hypomorphic variant in CDK13 as the cause of CHDFIDD with autosomal recessive inheritance through determination of an episignature.

Autosomal dominant CDK13-related disease is characterized by congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD). Heterozygous pathogenic variants, particularly missense variants in the kinase domain, have previously been described as disease causing. Using the determination of a methylation pattern and comparison with an established episignature, we reveal the first hypomorphic variant in the kinase domain of CDK13, leading to a never before described autosomal recessive form of CHDFIDD in a boy with characteristic features.

Fast, bioluminescent blinks attract group members of the nocturnal flashlight fish Anomalops katoptron (Bleeker, 1856).

Background: During their nighttime shoaling, the flashlight fish Anomalops katoptron produce fascinating, bioluminescent blink patterns, which have been related to the localization of food, determination of nearest neighbor distance, and initiation of the shoal's movement direction. Information transfer e.g.

Deep imaging of LepR stromal cells in optically cleared murine bone hemisections.

Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional (3D) architecture of tissues and deciphering cellular spatial interactions under physiological and pathological conditions. Deciphering the spatial interaction of leptin receptor-expressing (LepR) stromal cells with other compartments in the bone marrow is crucial for a deeper understanding of the stem cell niche and the skeletal tissue. In this study, we introduce an optimized protocol for the 3D analysis of skeletal tissues, enabling the visualization of hematopoietic and stromal cells, especially LepR stromal cells, within optically cleared bone hemisections.

Uncovering the genetic basis of antiviral polyketide limocrocin biosynthesis through heterologous expression.

Background: Streptomyces roseochromogenes NRRL 3504 produces clorobiocin, an aminocoumarin antibiotic that inhibits DNA replication. No other natural products have been isolated from this bacterium so far, despite the presence of a rich repertoire of specialized metabolite biosynthesis gene clusters (smBGCs) within its genome. Heterologous expression of smBGCs in suitable chassis speeds up the discovery of the natural products hidden behind these sets of genes.

Comparative assessment of Mini-FLOTAC, McMaster and semi-quantitative flotation for helminth egg examination in camel faeces.

Background: Faecal egg counts (FECs) are essential for diagnosing helminth infections and guiding treatment decisions. For camels, no evaluations of coproscopic methods regarding precision, sensitivity and correlation between individual and pooled faecal samples are currently available.

Methods: Here, 410 camel faecal samples were collected in 2022 from South Darfur State, Sudan, and analysed to compare the semi-quantitative flotation, McMaster and Mini-FLOTAC methods in terms of precision, sensitivity, inter-rater reliability and helminth egg count correlations, as well as the effects of pooling samples.

The world's most venomous spider is a species complex: systematics of the Sydney funnel-web spider (Atracidae: Atrax robustus).

The Sydney funnel-web spider Atrax robustus O. Pickard-Cambridge, 1877 is an iconic Australian species and considered among the most dangerously venomous spiders for humans. Originally described in 1877 from a single specimen collected in "New Holland", this spider has a complex taxonomic history.

Analysis of differential gene expression of PBMC for the in vitro detection of drug sensitization.

Background: The detection of drug-specific activation of T cells in the lymphocyte transformation test (LTT) is mainly based on cell proliferation or cytokine secretion. However, the LTT presents with a varying sensitivity and specificity. The aim of our study was to analyse the genome wide gene expression of PBMC to identify drug allergy-specific gene regulation patterns.

The Efficacy and Safety of Angiotensin II for Treatment of Vasoplegia in Critically Ill Patients: A Systematic Review.

Objectives: To summarize evidence regarding intravenous angiotensin II administration in critical illness and provide an updated understanding of its effects on various organ dysfunction and renin-angiotensin system (RAS) biomarkers.

Design: A systematic review.

Setting: A search of PubMed, Embase, and the Cochrane Library from inception to May 3, 2024.

Frontiers in laccase nanozymes-enabled colorimetric sensing: A review.

In recent years, nanozyme-based analytics have become popular. Among these, laccase nanozyme-based colorimetric sensors have emerged as simple and rapid colorimetric detection methods for various analytes, effectively addressing natural enzymes' stability and high-cost limitations. Laccase nanozymes are nanomaterials that exhibit inherent laccase enzyme-like activity.

Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.

The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists.

Informal care for people with dementia in Europe.

Introduction: Informal care estimates for use in health-economic models are lacking. We aimed to estimate the association between informal care time and dementia symptoms across Europe.

Methods: A secondary analysis was performed on 13,529 observations in 5,369 persons from 9 European pooled cohort or trial studies in community-dwelling persons with dementia.

Genetic predisposition to high circulating levels of interleukin 6 and risk for Alzheimer's disease. Discovery and replication.

Importance: Aging is accompanied by immune dysregulation, which has been implicated in Alzheimer's disease (AD) pathogenesis. Individuals who are genetically predisposed to elevated levels of proinflammatory mediators might be at increased risk for AD.

Objective: To investigate whether genetic propensity for higher circulating levels of interleukin 6 (IL-6) is associated with AD risk.

Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial.

Background: There are no approved oral disease-modifying treatments for Alzheimer's disease (AD).

Objectives: The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX®2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement.

Design: ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial.

Automated electronic health record-based screening for Fabry disease in unexplained left ventricular hypertrophy (FAPREV-HCM).

Background And Aims: Hypertrophic cardiomyopathy (HCM) has various aetiologies, including genetic conditions like Fabry disease (FD), a lysosomal storage disorder. FD prevalence in high-risk HCM populations ranges from 0.3% to 11.

Cost-utility analysis of MR imaging-guided transurethral ultrasound ablation for the treatment of low- to intermediate-risk localised prostate cancer.

Background: Magnetic resonance-guided transurethral ultrasound ablation (MR-TULSA) is a new focal therapy for treating localised prostate cancer that is associated with fewer adverse effects (AEs) compared with established treatments. To support large-scale clinical implementation, information about cost-effectiveness is required.

Objective: To evaluate the cost-utility of MR-TULSA compared with robot-assisted radical prostatectomy (RARP), external beam radiation therapy (EBRT) and active surveillance (AS) for patients with low- to favourable intermediate-risk localised prostate cancer.

Digital screening tool for the assessment of cognitive impairment in unsupervised setting-digiDEM-SCREEN: study protocol for a validation study.

Introduction: Dementia is one of the most relevant widespread diseases, with a prevalence of currently 55 million people with dementia worldwide. However, about 60-75% of people with dementia have not yet received a formal diagnosis. Asymptomatic screening of cognitive impairments using neuropsychiatric tests has been proven to efficiently enhance diagnosis rates.

Safe Implementation of Treatments in Stroke: a study on intravenous thrombolysis in patients over 80 years of age with acute ischaemic stroke.

Objectives: To investigate the safety and efficacy outcomes of intravenous thrombolysis (IVT) in patients aged >80 years with acute ischaemic stroke (AIS) after IVT was approved in this patient population in several European and non-European countries during 2018-2019.

Design: This is an observational registry study using prospectively collected data from the Safe Implementation of Treatment in Stroke (SITS) registry. Comparisons will be performed between patients treated post-approval (July 2018 to December 2021) period with those treated pre-approval (June 2015 to June 2018) period using propensity score matching (PSM).

Estimating the environmental burden of disease resulting from exposure to chemicals in European countries - potentials and challenges revealed in selected case studies.

Background: The increased use of chemicals leads to a continuous deposition of chemicals in the environment and to a continuous increase in exposure of the global and the European population. Comprehensive burden of disease analyses are however still missing for many countries.

Methods: Using the World Health Organization's Environmental Burden of Disease (EBD) approach and combining data from the European Human Biomonitoring (HBM) dashboard with disease and population data, we estimated the comprehensive attributable burden (AB) for the year 2021, in the best-case quantified by disability-adjusted life years (DALY).

Acute pulmonary embolism with and without hemodynamic instability (2003-2022): A Swiss nationwide epidemiological study.

Background: Data on the epidemiological burden of acute pulmonary embolism (PE) in Switzerland is unavailable. Knowledge gaps remain on trends in PE-related comorbidities, PE severity, and length of in-hospital stay (LOS) at a nationwide level.

Methods: We used nationwide, patient-level data including all patients aged 15 years or older hospitalized for PE in Switzerland from 2003 to 2022, amounting to N=180,600.

Effects of periodontal disease on the proteomic profile of the periodontal ligament.

Periodontal disease affects over 1 billion people globally. This study investigated how periodontitis affects the protein profile of the periodontal ligament (PDL) in rats. Eight Holtzman rats were divided into the control and experimental periodontitis groups.

Hyperacute Effects of Mitral Transcatheter Edge-to-Edge Repair on Left Ventricular Volumes and Functions.

Transcatheter edge-to-edge repair (TEER) is an effective intervention for high-risk patients with severe symptomatic mitral regurgitation (MR), but its acute impact on left ventricular (LV) function has not been well studied using advanced echocardiographic techniques. This study investigated the immediate effects of TEER on LV volumes and functions, as well as their influence on mid-term outcomes, using high-resolution 3D transesophageal echocardiography. In 80 patients undergoing TEER for severe MR (mean age 79±8 years, 49% with primary MR), LV end-diastolic volume (LVEDV) and stroke volume significantly decreased (161±61 to 147±54 ml and 69±18 to 50±15 ml, respectively), while end-systolic volume increased (92±60 to 97±45 ml; p<0.

Balloon atrioseptostomy for transposition of the great arteries in Europe: characteristics and outcomes.

Introduction And Objectives: Balloon atrial septostomy (BAS) improves oxygenation in neonates with transposition of the great arteries (TGA) and restrictive foramen ovale. Currently, there is a global shortage of dedicated BAS catheters, while new unmarked catheters have recently become available at some European centers. This study aimed to characterize BAS outcomes using the currently available BAS catheters in Europe.

Risk of colorectal cancer associated with frequency of colorectal polyp diagnosis in relatives.

Background & Aims: We aimed to evaluate the association of frequency of polyp diagnosis in relatives with the risk of overall and early-onset colorectal cancer (CRC).

Methods: We leveraged data from nationwide Swedish family cancer datasets (1964-2018) to calculate standardized incidence ratios (SIRs) for individuals with a family history of polyp by frequency of polyp diagnosis in family members.

Results: We followed up 11,676,043 individuals for up to 54 years.

Accounting for differential exclusions in the NordICC trial discloses stronger-than-reported effects of screening colonoscopy.

Objective: Recently, results on colorectal cancer (CRC) incidence and mortality reduction by the offer of screening colonoscopy were reported for the first time from a randomized controlled trial (RCT), the Nordic-European Initiative on Colorectal Cancer (NordICC) trial. Despite randomization, there was a substantially lower proportion of post-randomization exclusions of CRC cases due to cancer registry-recorded date of diagnosis before recruitment in the invited group than in the usual-care group. We aimed to evaluate the impact of such differential exclusions on the trial's effect estimates on CRC risk.