An artificial intelligence-assisted clinical framework to facilitate diagnostics and translational discovery in hematologic neoplasia.

Background: The increasing volume and intricacy of sequencing data, along with other clinical and diagnostic data, like drug responses and measurable residual disease, creates challenges for efficient clinical comprehension and interpretation. Using paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) as a use case, we present an artificial intelligence (AI)-assisted clinical framework clinALL that integrates genomic and clinical data into a user-friendly interface to support routine diagnostics and reveal translational insights for hematologic neoplasia.

Methods: We performed targeted RNA sequencing in 1365 cases with haematological neoplasms, primarily paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) from the AIEOP-BFM ALL study.

Separation and Analysis of Connected, Micrometer-Sized, High-Frequency Damage on Glass Plates due to Laser-Accelerated Material Fragments in Vacuum.

In this paper, we present a new processing method, called MOSES-Impacts, for the detection of micrometer-sized damage on glass plate surfaces. It extends existing methods by a separation of damaged areas, called impacts, to support state-of-the-art recycling systems in optimizing their parameters. These recycling systems are used to repair process-related damages on glass plate surfaces, caused by accelerated material fragments, which arise during a laser-matter interaction in a vacuum.

The landscape of cytogenetic and molecular genetic methods in diagnostics for hematologic neoplasia.

Improvements made during the last decades in the management of patients with hematologic neoplasia have resulted in increase of overall survival. These advancements have become possible through progress in our understanding of genetic basis of different hematologic malignancies and their role in the current risk-adapted treatment protocols. In this review, we provide an overview of current cytogenetic and molecular genetic methods, commonly used in the genetic characterization of hematologic malignancies, describe the current developments in the cytogenetic and molecular diagnostics, and give an outlook into their future development.

Chemotherapy-Free Targeted Anti-BCR-ABL+ Acute Lymphoblastic Leukemia Therapy May Benefit the Heart.

Targeted therapies are currently considered the best cost-benefit anti-cancer treatment. In hematological malignancies, however, relapse rates and non-hematopoietic side effects including cardiotoxicity remain high. Here, we describe significant heart damage due to advanced acute lymphoblastic leukemia (ALL) with t(9;22) encoding the bcr-abl oncogene (BCR-ABL+ ALL) in murine xenotransplantation models.

Increased prostaglandin-D2 in male STAT3-deficient hearts shifts cardiac progenitor cells from endothelial to white adipocyte differentiation.

Cardiac levels of the signal transducer and activator of transcription factor-3 (STAT3) decline with age, and male but not female mice with a cardiomyocyte-specific STAT3 deficiency conditional knockout (CKO) display premature age-related heart failure associated with reduced cardiac capillary density. In the present study, isolated male and female CKO-cardiomyocytes exhibit increased prostaglandin (PG)-generating cyclooxygenase-2 (COX-2) expression. The PG-degrading hydroxyprostaglandin-dehydrogenase-15 (HPGD) expression is only reduced in male cardiomyocytes, which is associated with increased prostaglandin D2 (PGD2) secretion from isolated male but not female CKO-cardiomyocytes.

Common genetic predisposition for heart failure and cancer.

Cardiovascular diseases and cancer are major causes of mortality in industrialized societies. They share common risk factors (e.g.

Outcome in German and South African peripartum cardiomyopathy cohorts associates with medical therapy and fibrosis markers.

Aims: This study aims to compare the clinical course of peripartum cardiomyopathy (PPCM) cohorts from Germany (G-PPCM) and South Africa (SA-PPCM) with fibrosis-related markers to get insights into novel pathomechanisms of PPCM.

Methods And Results: G-PPCM (n = 79) and SA-PPCM (n = 72) patients and healthy pregnancy-matched women from Germany (n = 56) and South Africa (n = 40) were enrolled. Circulating levels of procollagen type-I (PINP) and type-III (PIIINP) N-terminal propeptides, soluble ST2, galectin-3, and full-length and cleaved osteopontin (OPN) were measured at diagnosis (baseline) and 6 months of follow-up.

Data on left ventricular expression of STAT3 and AKT in transgenic mouse models with B16F10 melanoma.

The dataset describes protein expression of phosphorylated and total signal transducer and activator of transcription 3 (STAT3), protein kinase B (AKT) and suppressor of cytokine signalling 3 (SOCS3) in left ventricular tissue (LV) from healthy and B16F10 melanoma tumour-bearing (B16F10-TM) wildtype (WT) mice, mice with cardiomyocyte-specific constitutively active AKT transgene (AKTtg) and mice with cardiomyocyte-restricted deletion of STAT3 (CKO) analysed in Western blot and/or fluorescence microscopy experiments. The data presented in this article are related to the research paper entitled "Modulation of cardiac AKT and STAT3 signalling in preclinical cancer models and their impact on the heart", available in Biochim. Biophys.

Intersection AEB implementation strategies for left turn across path crashes.

Left turn across path with traffic from the opposite direction (LTAP/OD) is the second most frequent car-to-car intersection crash type after straight crossing path (SCP) in Germany and the United States. Intersection automated emergency braking (AEB) for passenger cars can address these crashes. This study investigates 2 implementation strategies of intersection AEB addressing LTAP/OD crashes: (1) only the turning car is equipped with an intersection AEB and (2) turning and straight-heading cars are equipped with an intersection AEB.

Modulation of cardiac AKT and STAT3 signalling in preclinical cancer models and their impact on the heart.

Background: Advanced cancer induces fundamental cardiac changes and promotes body wasting and heart failure. We evaluated the impact of cancer on major cardiac signalling pathways, and resulting consequences for the heart.

Methods And Results: Metastatic melanoma disease was induced in male C57BL/6 N mice by intraperitoneal injection of the melanoma cell line B16F10 and lead to cardiac atrophy and heart failure.

Costs and cost-effectiveness of three point-of-use water treatment technologies added to community-based treatment of severe acute malnutrition in Sindh Province, Pakistan.

Background: Severe acute malnutrition (SAM) is a major global public health concern. Despite the cost-effectiveness of treatment, ministries of health are often unable to commit the required funds which limits service coverage.

Objective: A randomised controlled trial was conducted in Sindh Province, Pakistan, to assess whether adding a point of use water treatment to the treatment of SAM without complications improved its cost-effectiveness.

Point-of-use water treatment improves recovery rates among children with severe acute malnutrition in Pakistan: results from a site-randomized trial.

Objective: To evaluate effectiveness of point-of-use water treatment in improving treatment of children affected by severe acute malnutrition (SAM).

Design: Programme sites were randomized to one of four intervention arms: (i) standard SAM treatment; (ii) SAM treatment plus flocculent/disinfectant water treatment; (iii) SAM treatment plus chlorine disinfectant; or (iv) SAM treatment plus ceramic water filter. Outcome measures were calculated based on participant status upon exit or after 120d of enrolment, whichever came first.

Children who are both wasted and stunted are also underweight and have a high risk of death: a descriptive epidemiology of multiple anthropometric deficits using data from 51 countries.

Background: Wasting and stunting are common. They are implicated in the deaths of almost two million children each year and account for over 12% of disability-adjusted life years lost in young children. Wasting and stunting tend to be addressed as separate issues despite evidence of common causality and the fact that children may suffer simultaneously from both conditions ().

The cost of preventing undernutrition: cost, cost-efficiency and cost-effectiveness of three cash-based interventions on nutrition outcomes in Dadu, Pakistan.

Cash-based interventions (CBIs) increasingly are being used to deliver humanitarian assistance and there is growing interest in the cost-effectiveness of cash transfers for preventing undernutrition in emergency contexts. The objectives of this study were to assess the costs, cost-efficiency and cost-effectiveness in achieving nutrition outcomes of three CBIs in southern Pakistan: a 'double cash' (DC) transfer, a 'standard cash' (SC) transfer and a 'fresh food voucher' (FFV) transfer. Cash and FFVs were provided to poor households with children aged 6-48 months for 6 months in 2015.

Impact evaluation of different cash-based intervention modalities on child and maternal nutritional status in Sindh Province, Pakistan, at 6 mo and at 1 y: A cluster randomised controlled trial.

Background: Cash-based interventions (CBIs), offer an interesting opportunity to prevent increases in wasting in humanitarian aid settings. However, questions remain as to the impact of CBIs on nutritional status and, therefore, how to incorporate them into emergency programmes to maximise their success in terms of improved nutritional outcomes. This study evaluated the effects of three different CBI modalities on nutritional outcomes in children under 5 y of age at 6 mo and at 1 y.

Insulin supplementation attenuates cancer-induced cardiomyopathy and slows tumor disease progression.

Advanced cancer induces fundamental changes in metabolism and promotes cardiac atrophy and heart failure. We discovered systemic insulin deficiency in cachectic cancer patients. Similarly, mice with advanced B16F10 melanoma (B16F10-TM) or colon 26 carcinoma (C26-TM) displayed decreased systemic insulin associated with marked cardiac atrophy, metabolic impairment, and function.

Low STAT3 expression sensitizes to toxic effects of β-adrenergic receptor stimulation in peripartum cardiomyopathy.

Aims: The benefit of the β1-adrenergic receptor (β1-AR) agonist dobutamine for treatment of acute heart failure in peripartum cardiomyopathy (PPCM) is controversial. Cardiac STAT3 expression is reduced in PPCM patients. Mice carrying a cardiomyocyte-restricted deletion of STAT3 (CKO) develop PPCM.

Cardiomyocytes display low mitochondrial priming and are highly resistant toward cytotoxic T-cell killing.

Following heart transplantation, alloimmune responses can cause graft rejection by damaging donor vascular and parenchymal cells. However, it remains unclear whether cardiomyocytes are also directly killed by immune cells. Here, we used two-photon microscopy to investigate how graft-specific effector CD8(+) T cells interact with cardiomyocytes in a mouse heart transplantation model.

The REFANI Pakistan study--a cluster randomised controlled trial of the effectiveness and cost-effectiveness of cash-based transfer programmes on child nutrition status: study protocol.

Background: Cash-based transfer programmes are an emerging strategy in the prevention of wasting in children, especially targeted at vulnerable households during periods of food insecurity or during emergencies. However, the evidence surrounding the use of either cash or voucher transfer programmes in the humanitarian context and on nutritional outcomes is elusive. More evidence is needed not only to inform the global community of practice on best practices in humanitarian settings, but also to help strengthen national mitigation responses.

Learning local objective functions for robust face model fitting.

Model-based techniques have proven to be successful in interpreting the large amount of information contained in images. Associated fitting algorithms search for the global optimum of an objective function, which should correspond to the best model fit in a given image. Although fitting algorithms have been the subject of intensive research and evaluation, the objective function is usually designed ad hoc, based on implicit and domain-dependent knowledge.

Interaction of quercetin glucosides with the intestinal sodium/glucose co-transporter (SGLT-1).

Recently it has been postulated that flavonoid glucosides may be absorbed by the small intestine via the SGLT-1. Therefore, we applied an in vitro mucosal uptake method to investigate mucosal uptake of the non-metabolisable glucose analogue methyl-alpha-D-glucopyranoside (MDG) as influenced by quercetin-3-glucoside (isoquercitrin) and quercetin-4'-glucoside (spiraeosid). We found that both glucosides significantly inhibited SGLT-1-mediated MDG uptake whereas the aglycon quercetin or the quercetin-3-rhamnoglucoside (rutin) were ineffective.

[The dose-dependent effects of oral premedication with midazolam].

Objective: The aim of this study was to examine the psychological effects, well-being and side effects after various doses of oral midazolam medication.

Methods: After informed consent has been obtained and following the approval by the institutional ethical committee, 80 adult patients in the ASA physical status I and II were randomly assigned to one of five different premedication groups: 3.75, 7.