Expression of renal cell markers and detection of 3p loss links endolymphatic sac tumor to renal cell carcinoma and warrants careful evaluation to avoid diagnostic pitfalls.

Endolymphatic sac tumor (ELST) is a rare neoplasm arising in the temporal petrous region thought to originate from endolymphatic sac epithelium. It may arise sporadically or in association with Von-Hippel-Lindau syndrome (VHL). The ELST prevalence in VHL ranges from 3 to 16% and may be the initial presentation of the disease.

XBP1-KLF9 Axis Acts as a Molecular Rheostat to Control the Transition from Adaptive to Cytotoxic Unfolded Protein Response.

Transcription factor XBP1s, activated by endoplasmic reticulum (ER) stress in a dose-dependent manner, plays a central role in adaptive unfolded protein response (UPR) via direct activation of multiple genes controlling protein refolding. Here, we report that elevation of ER stress above a critical threshold causes accumulation of XBP1s protein sufficient for binding to the promoter and activation of a gene encoding a transcription factor KLF9. In comparison to other XBP1s targets, KLF9 promoter contains an evolutionary conserved lower-affinity binding site that requires higher amounts of XBP1s for activation.

Increased Risk for Malignancies in 131 Affected Mutation Carriers.

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a negative immune regulator on the surface of T cells. In humans, heterozygous germline mutations in can cause an immune dysregulation syndrome. The phenotype comprises a broad spectrum of autoinflammatory, autoimmune, and immunodeficient features.

Inhibition of the aryl hydrocarbon receptor/polyamine biosynthesis axis suppresses multiple myeloma.

Polyamine inhibition for cancer therapy is, conceptually, an attractive approach but has yet to meet success in the clinical setting. The aryl hydrocarbon receptor (AHR) is the central transcriptional regulator of the xenobiotic response. Our study revealed that AHR also positively regulates intracellular polyamine production via direct transcriptional activation of 2 genes, ODC1 and AZIN1, which are involved in polyamine biosynthesis and control, respectively.

Detrimental Effect of Broad-spectrum Antibiotics on Intestinal Microbiome Diversity in Patients After Allogeneic Stem Cell Transplantation: Lack of Commensal Sparing Antibiotics.

Background: Maintaining gastrointestinal (GI) microbiome diversity plays a key role during allogeneic stem cell transplantation (ASCT), and loss of diversity correlates with acute GI graft versus host disease (GvHD) and poor outcomes.

Methods: In this retrospective analysis of 161 ASCT patients, we used serial analyses of urinary 3-indoxyl sulfate (3-IS) levels and GI microbiome parameters within the first 10 days after ASCT to identify potential commensal microbiota-sparing antibiotics. Based on antibiotic activity, we formed 3 subgroups (Rifaximin without systemic antibiotics, Rifaximin with systemic antibiotics, and Ciprofloxacin/Metronidazole with/without systemic antibiotics).

The influence of glucocorticoid receptor single nucleotide polymorphisms on outcome after haematopoietic stem cell transplantation.

Haematopoietic stem cell transplantation (HSCT) remains the only cure for most haematological malignancies, however, the mortality rate remains high. Complications after HSCT include relapse, graft versus host disease (GvHD), graft rejection and infection. Over the last few years several groups, have demonstrated that non-HLA gene polymorphisms can be predictive of outcome after HSCT.

Insights into the variability of microbial community composition and micropollutant degradation in diverse biological wastewater treatment systems.

The biological potential of conventional wastewater treatment plants to remove micropollutants mainly depends on process conditions and the predominant microbial community. To explore this dependence and to connect the occurrence of genera with operating conditions, five pilot-scale reactors with different process conditions were combined into two reactor cascades and fed with the effluent of the primary clarifier of a municipal WWTP. All reactors and the WWTP were analyzed for the removal of 33 micropollutants by LC-MS/MS and the presence of the microbial community using 16S rRNA gene sequencing.

Relative Impact of HLA Matching and Non-HLA Donor Characteristics on Outcomes of Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome.

Increasing donor-recipient HLA disparity is associated with negative outcomes of allogeneic hematopoietic stem cell transplantation (HSCT), but its comparative relevance amid non-HLA donor characteristics is not well established. We addressed this question in 3215 HSCTs performed between 2005 and 2013 in Germany for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Donors were HLA-matched related (MRD; n = 872) or unrelated (10/10 MUD, n = 1553) or HLA-mismatched unrelated (<10/10 MMUD, n = 790).

The eGVHD App has the potential to improve the accuracy of graft-versus-host disease assessment: a multicenter randomized controlled trial.

Graft--host disease (GvHD) assessment has been shown to be a challenge for healthcare professionals, leading to the development of the eGVHD App (www.uzleuven.be/egvhd).

Camptothecin exhibits topoisomerase1-independent KMT1A suppression and myogenic differentiation in alveolar rhabdomyosarcoma cells.

Alveolar rhabdomyosarcoma (aRMS) is an aggressive subtype of the most common soft tissue cancer in children. A hallmark of aRMS tumors is incomplete myogenic differentiation despite expression of master myogenic regulators such as MyoD. We previously reported that histone methyltransferase KMT1A suppresses MyoD function to maintain an undifferentiated state in aRMS cells, and that loss of KMT1A is sufficient to induce differentiation and suppress malignant phenotypes in these cells.

EBMT-NIH-CIBMTR Task Force position statement on standardized terminology & guidance for graft-versus-host disease assessment.

Several international recommendations address the assessment of graft-versus-host disease (GvHD) after hematopoietic cell transplantation (HCT). This position statement by GvHD experts from the European Society for Blood and Marrow Transplantation (EBMT), the National Institutes of Health (NIH) and the Center for International Blood and Marrow Transplant Research (CIBMTR) reviews the existing guidelines for both acute and chronic GvHD, addresses potential confusions that arise in daily practice and proposes consensus definitions for many key terms. We provide a historical perspective on the currently available guidelines and recommend the Mount Sinai Acute GvHD International Consortium (MAGIC) criteria for acute GvHD and the NIH 2014 criteria for chronic GvHD as the most comprehensive and detailed criteria available.

Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects.

Background: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in human subjects.

Objective: We sought to characterize the penetrance, clinical features, and best treatment options in 133 CTLA4 mutation carriers.

Personalized Knowledge Transfer for Caregiving Relatives.

Caregiving relatives have to manage very diverse tasks and need a lot of care-relevant knowledge. For most of them it is not easy to find the knowledge required. Thus, a personalized knowledge transfer for caregiving relatives is necessary.

Psychosocial impact, perceived stress and learning effect in undergraduate dental students during transition from pre-clinical to clinical education.

Introduction: This study aimed to develop a suitable instrument for a comprehensive quantitative and qualitative assessment of perceived psychosocial impact, levels of stress and learning effect in undergraduate dental students during the transition from pre-clinical to clinical education. These findings might improve curricular structures and didactic organisation during this period.

Materials And Methods: At the beginning of their first clinical year, undergraduate dental students were asked to complete an anonymous forty-item questionnaire.

Quality of life and sexual well-being in patients with a Fontan circulation: An explorative pilot study with a mixed method design.

Objective: To get an impression of the quality of life (QOL) and sexual well-being in the Fontan population, and to generate hypotheses for future research.

Methods: For this cross-sectional pilot study, questionnaires regarding health-related QOL, sexual function and fertility/pregnancy were completed by 21 patients with a Fontan circulation >16 years old, followed at the University Medical Center Groningen, the Netherlands. Semi-structured qualitative interviews were conducted in 8 patients.

FOXQ1 controls the induced differentiation of melanocytic cells.

Oncogenic transcription factor FOXQ1 has been implicated in promotion of multiple transformed phenotypes in carcinoma cells. Recently, we have characterized FOXQ1 as a melanoma tumor suppressor that acts via repression of N-cadherin gene, and invasion and metastasis. Here we report that FOXQ1 induces differentiation in normal and transformed melanocytic cells at least partially via direct transcriptional activation of MITF gene, melanocytic lineage-specific regulator of differentiation.

Biological evaluation of subgingivally placed direct resin composite materials.

Placement of composite resin restorations in deep subgingival cavities can damage surrounding soft tissues. In addition, commonly used resin-based composites (RBCs) might interfere with wound healing and periodontal health. To clarify cellular interactions with RBCs, we used an MTT assay to investigate adhesion of primary human gingival fibroblasts and human osteoblasts (hFOB 1.

Biomarkers in chronic graft-versus-host disease: quo vadis?

Biomarkers are increasingly used for diagnosis and treatment of transplant-related complications including the first biomarker-driven interventional trials of acute graft-versus-host disease (GvHD). In contrast, the development of biomarkers of chronic GvHD (cGvHD) has lagged behind due to a broader variety of manifestations, overlap with acute GvHD, a greater variation in time to onset and maximum severity, and lack of sufficient patient numbers within prospective trials. An international workshop organized by a North-American and European consortium was held in Marseille in March 2017 with the goal to discuss strategies for future biomarker development to guide cGvHD therapy.

Authors' Reply.

Authors' Reply to the Letter to the Editor by Montgomery et al (Identification of Germline Variants in Tumor Genomic Sequencing Analysis. J Mol Diagn 2017, 19:XXXX-XXXX).

First Report of Prenatal Ascertainment of a Fetus With Homozygous Loss of the SOX10 Gene and Phenotypic Correlation by Autopsy Examination.

The SOX10 gene plays a vital role in neural crest cell development and migration. Abnormalities in SOX10 are associated with Waardenburg syndrome Types II and IV, and these patients have recognizable clinical features. This case report highlights the first ever reported homozygous loss of function of the SOX10 gene in a human.

Quantitative drinking water arsenic concentrations in field environments using mobile phone photometry of field kits.

Arsenic (As) groundwater contamination is common yet spatially heterogeneous within most environments. It is therefore necessary to measure As concentrations to determine whether a water source is safe to drink. Measurement of As in the field involves using a test strip that changes color in the presence of As.

The association between acute graft-versus-host disease and antimicrobial peptide expression in the gastrointestinal tract after allogeneic stem cell transplantation.

Intestinal microbiota disruption is associated with acute gastrointestinal (GI) Graft-versus-Host Disease (GvHD) and poor outcome after allogeneic stem cell transplantation (ASCT). Here, in a retrospective analysis of 200 patients undergoing ASCT at the Regensburg University Medical Center, we assessed the relative expression of Paneth cell antimicrobial peptides (AMPs), Human Defensins (HD) 5 and 6 and regenerating islet-derived 3α (Reg3α), in 292 human intestinal biopsies as well as Reg3α serum levels in relation to acute GI GvHD. In the absence of GI GvHD, the relative expression of Paneth cell AMPs was significantly higher in the small intestine (duodenum to ileum) than in the stomach and large intestine (cecum to rectum) for Reg3α (p≤0.

Potential Role of the PD-1/PD-L1 Axis in the Immune Regulation of Chronic GVHD.

Background: Antibodies blocking the PD-1/PD-L1 axis have been shown to have substantial antitumor effects also in the treatment of Hodgkin's lymphoma (HL) relapsing after conventional chemotherapy or even autologous hematopoietic stem cell transplantation (autoHSCT). In the case of allogeneic HSCT (alloHSCT), this treatment bears the risk of inducing graft-versus-host disease (GVHD). So far, only a small number of patients who developed acute GVHD after PD-1 antibody administration are described in the literature.