Epigenetic insights to pediatric uropathology: Celebrating the fundamental biology vision of Tony Khoury.

Introduction: Many pediatric urology conditions affect putatively normal tissues or appear too commonly to be based solely on specific DNA mutations. Understanding epigenetic mechanisms in pediatric urology, therefore, has many implications that can impact cell and tissue responses to settings, such as environmental and hormonal influences on urethral development, uropathogenic infections, obstructive stimuli, all of which originate externally or extracellularly. Indeed, the cell's response to external stimuli is often mediated epigenetically.

Etiologies and predictors of mortality in an all-comer population of patients with non-ischemic heart failure.

Background: Despite progress in diagnosis and therapy of heart failure (HF), etiology and risk stratification remain elusive in many patients.

Methods: The My Biopsy HF Study (German clinical trials register number: DRKS22178) is a retrospective monocentric study investigating an all-comer population of patients with unexplained HF based on a thorough workup including endomyocardial biopsy (EMB).

Results: 655 patients (70.

Outcomes After Transcatheter Mitral Valve Replacement According to Regurgitation Etiology.

Background: Whether transcatheter mitral valve replacement (TMVR) devices perform similarly with respect to the underlying mitral regurgitation (MR) etiology remains unknown. The aim of the present analysis was to assess outcomes of TMVR according to the MR underlying etiology among the CHoice of OptImal transCatheter trEatment for Mitral Insufficiency (CHOICE-MI) registry.

Methods: Of 746 patients, 229 patients (30.

EZH2 and matrix co-regulate phenotype and KCNB2 expression in bladder smooth muscle cells.

Background: Partial bladder outlet obstruction (PBO) is a widespread cause of urinary dysfunction and patient discomfort, resulting in immense health care costs. Previously, we found that obstruction is associated with altered regulation of epigenetic machinery and altered function. Here we examined if PBO and chronic bladder obstructive disease (COBD) affect epigenetic marks in a proof of principle gene and explored mechanisms of its epigenetic regulation using models.

Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer.

Background: Treatment for patients with recurrent ovarian cancer has been mainly based on systemic therapy. The role of secondary cytoreductive surgery is unclear.

Methods: We randomly assigned patients with recurrent ovarian cancer who had a first relapse after a platinum-free interval (an interval during which no platinum-based chemotherapy was used) of 6 months or more to undergo secondary cytoreductive surgery and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone.

Should Contact Bans Have Been Lifted More in Germany?: A Quantitative Prediction of Its Effects.

Many countries consider the lifting of restrictions of social contacts (RSC). We quantify the effects of RSC for Germany. We initially employ a purely statistical approach to predicting prevalence of Covid-19 if RSC had been upheld after 20 April.

Prognostic Significance of Interferon-γ and Its Signaling Pathway in Early Breast Cancer Depends on the Molecular Subtypes.

Interferons are crucial for adaptive immunity and play an important role in the immune landscape of breast cancer. Using microarray-based gene expression analysis, we examined the subtype-specific prognostic significance of interferon-γ (IFN-γ) as a single gene as well as an IFN-γ signature covering the signaling pathway in 461 breast cancer patients. Prognostic significance of IFN-γ, as well as the IFN-γ signature for metastasis-free survival (MFS), were examined using Kaplan-Meier as well as univariate and multivariate Cox regression analyses in the whole cohort and in different molecular subtypes.

Screening and assessment tools for gaming disorder: A comprehensive systematic review.

The inclusion of gaming disorder (GD) as an official diagnosis in the ICD-11 was a significant milestone for the field. However, the optimal measurement approaches for GD are currently unclear. This comprehensive systematic review aimed to identify and evaluate all available English-language GD tools and their corresponding evidence.

The impact of intraocular pressure fluctuations and other factors on conversion of ocular hypertension to primary open-angle glaucoma.

Purpose: To evaluate the role of intraocular pressure (IOP) fluctuations and other factors on conversion of ocular hypertension to open-angle glaucoma (OAG) within a retrospective, longitudinal cohort study.

Patients And Methods: The study population included patients with ocular hypertension defined by IOP > 21 mmHg with normal appearing optic discs and no visual field defect. IOP fluctuation, mean and maximum were examined in 61 eyes over a follow-up period of 36 months (standard deviation (SD) 24).

Cardiovascular risk factors are important determinants of platelet-dependent thrombin generation in adult survivors of childhood cancer.

Cardiovascular disease is the most frequent non-malignant cause of morbidity and mortality in adult survivors of childhood or adolescent cancer. Thrombin generation (TG) analysis gives insight in hypercoagulability as an important mechanism linked to cardiovascular risk factors (CVRFs). In 200 individuals, from the cardiac and vascular late sequelae in long-term survivors of childhood cancer study, TG in platelet-rich plasma (PRP) and platelet-free plasma (PFP) at 1pM tissue factor was investigated.

Clinical trial of the D.E.L.P.H.I.N. speech treatment for children and adolescents who stutter.

The present trial investigated the D.E.L.

Association of ocular, cardiovascular, morphometric and lifestyle parameters with retinal nerve fibre layer thickness.

Background: Glaucoma is a neurodegenerative disease, leading to thinning of the retinal nerve fibre layer (RNFL). The exact influence of ocular, cardiovascular, morphometric, lifestyle and cognitive factors on RNFL thickness (RNFLT) is unknown and was analysed in a subgroup of the Gutenberg Health Study (GHS).

Methods: Global peripapillary RNFLT was measured in 3224 eyes of 1973 subjects (49% female) using spectral-domain optical coherence tomography (SD-OCT).

Clinical Determinants of Thrombin Generation Measured in Presence and Absence of Platelets-Results from the Gutenberg Health Study.

The tendency of a plasma sample to generate thrombin, a central enzyme in blood coagulation, might be an important indicator of prothrombotic risk linked to cardiovascular disease (CVD), but the presence of platelets may be a critical determinant. Clinical data, laboratory markers and thrombin generation (TG), investigated in both platelet-rich plasma (PRP) and platelet-free plasma (PFP) at 1 pM TF, were available in 407 individuals from the Gutenberg Health Study. Given the well-known effect of anticoagulants on TG, subjects taking anticoagulants ( = 15) have been excluded resulting in 392 subjects for further analysis.

Prognostic impact of CD4-positive T cell subsets in early breast cancer: a study based on the FinHer trial patient population.

Background: The clinical importance of tumor-infiltrating cluster of differentiation 4 (CD4) T cells is incompletely understood in early breast cancer. We investigated the clinical significance of CD4, forkhead box P3 (FOXP3), and B cell attracting chemokine leukocyte chemoattractant-ligand (C-X-C motif) 13 (CXCL13) in early breast cancer.

Methods: The study is based on the patient population of the randomized FinHer trial, where 1010 patients with early breast cancer were randomly allocated to adjuvant chemotherapy containing either docetaxel or vinorelbine, and human epidermal growth factor receptor 2 (HER2)-positive patients were also allocated to trastuzumab or no trastuzumab.

Sunitinib added to FOLFIRI versus FOLFIRI in patients with chemorefractory advanced adenocarcinoma of the stomach or lower esophagus: a randomized, placebo-controlled phase II AIO trial with serum biomarker program.

Background: As a multi-targeted anti-angiogenic receptor tyrosine kinase (RTK) inhibitor sunitinib (SUN) has been established for renal cancer and gastrointestinal stromal tumors. In advanced refractory esophagogastric cancer patients, monotherapy with SUN was associated with good tolerability but limited tumor response.

Methods: This double-blind, placebo-controlled, multicenter, phase II clinical trial was conducted to evaluate the efficacy, safety and tolerability of SUN as an adjunct to second and third-line FOLFIRI (NCT01020630).

Transcatheter valve-in-ring implantation of a repositionable valve system for treatment of severe mitral regurgitation.

Introduction: Years after mitral valve surgery, progressive degeneration of reconstructed mitral valves or bioprostheses might lead to severe mitral valve regurgitation. Patients with significant comorbidity, or impaired left ventricular function are poor candidates for redo surgery at an acceptable risk at that later time point.

Methods And Results: This study reports the first-in-man transapical valve-in-ring implantations in the mitral position of the fully repositionable Lotus valve system approved for transcatheter aortic valve replacement in Europe.

Reconstruction of Protein Networks Using Reverse-Phase Protein Array Data.

In this chapter, we describe an approach to reconstruct cellular signaling networks based on measurements of protein activation after different stimulation experiments. As experimental platform reverse-phase protein arrays (RPPA) are used. RPPA allow the measurement of proteins and phosphoproteins across many samples in parallel with minimal sample consumption using a panel of highly target protein-specific antibodies.

Gemcitabine plus sorafenib versus gemcitabine alone in advanced biliary tract cancer: a double-blind placebo-controlled multicentre phase II AIO study with biomarker and serum programme.

Background: Since sorafenib has shown activity in different tumour types and gemcitabine regimens improved the outcome for biliary tract cancer (BTC) patients, we evaluated first-line gemcitabine plus sorafenib in a double-blind phase II study.

Patients And Methods: 102 unresectable or metastatic BTC patients with histologically proven adenocarcinoma of gallbladder or intrahepatic bile ducts, Eastern Cooperative Oncology Group (ECOG) 0-2 were randomised to gemcitabine (1000 mg/m2 once weekly, first 7-weeks+1-week rest followed by once 3-weeks+1-week rest) plus sorafenib (400 mg twice daily) or placebo. Treatment continued until progression or unacceptable toxicity.

Bacteriology of aspiration pneumonia in patients with acute coma.

Loss of protective airway reflexes in patients with acute coma puts these patients at risk of aspiration pneumonia complicating the course of the primary disease. Available data vary considerably with regard to bacteriology, role of anaerobic bacteria, and antibiotic treatment. Our objective was to research the bacteriology of aspiration pneumonia in acute coma patients who were not pre-treated with antibiotics or hospitalized within 30 days prior to the event.

Synthesis, properties, and biological activity of boranophosphate analogs of the mRNA cap: versatile tools for manipulation of therapeutically relevant cap-dependent processes.

Modified mRNA cap analogs aid in the study of mRNA-related processes and may enable creation of novel therapeutic interventions. We report the synthesis and properties of 11 dinucleotide cap analogs bearing a single boranophosphate modification at either the α-, β- or γ-position of the 5',5'-triphosphate chain. The compounds can potentially serve either as inhibitors of translation in cancer cells or reagents for increasing expression of therapeutic proteins in vivo from exogenous mRNAs.

Targeting the tumor mutanome for personalized vaccination therapy.

Next generation sequencing enables identification of immunogenic tumor mutations targetable by individualized vaccines. In the B16F10 melanoma system as pre-clinical proof-of-concept model, we found a total of 563 non-synonymous expressed somatic mutations. Of the mutations we tested, one third were immunogenic.