Atypical cancer risk profile in carriers of Italian founder BRCA1 variant p.His1673del: Implications for classification and clinical management.

Background: BRCA1:c.5017_5019del (p.His1673del) is a founder variant relatively frequent in Northern Italy.

Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline sequence variants.

The ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer (HBOP) Variant Curation Expert Panel (VCEP) is composed of internationally recognized experts in clinical genetics, molecular biology and variant interpretation. This VCEP made specifications for ACMG/AMP guidelines for the ataxia telangiectasia mutated () gene according to the Food and Drug Administration (FDA)-approved ClinGen protocol. These gene-specific rules for were modified from the American College of Medical Genetics and Association for Molecular Pathology (ACMG/AMP) guidelines and were tested against 33 variants of various types and classifications in a pilot curation phase.

Excellent capture of NO functioning at RT and lower pressure by utilizing an NaCaA-85 zeolite.

We have found an efficient adsorption feature provided by an NaCaA-85 zeolite for NO even at 298 K and at lower pressures: NO adsorption capacities of 1.33 mmol g and 4.69 mmol g under respective pressures of 0.

Challenges and approaches to calibrating patient phenotype as evidence for cancer gene variant classification under ACMG/AMP guidelines.

Since first publication of the American College of Medical Genetics and Genomics/Association for Medical Pathology (ACMG/AMP) variant classification guidelines, additional recommendations for application of certain criteria have been released (https://clinicalgenome.org/docs/), to improve their application in the diagnostic setting. However, none have addressed use of the PS4 and PP4 criteria, capturing patient presentation as evidence towards pathogenicity.

Specifications of the ACMG/AMP Variant Classification Guidelines for Germline Variant Curation.

Germline pathogenic variants in predispose individuals to develop a variety of benign and malignant tumors. Accurate variant curation and classification is essential for reliable diagnosis of -related tumor predisposition and identification of individuals who may benefit from surveillance. Since 2015, most labs have followed the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) sequence variant classification guidelines for germline variant curation.

Successful treatment of multiple microbleeds in a large area of the small bowel by transcatheter arterial embolization using imipenem/cilastatin as embolization material.

A 44-year-old man with chronic idiopathic pseudo-intestinal obstruction and lumbar disc herniation presented with orthostatic dizziness, black vomiting, and stools. He was suspected to have an ulcer caused by nonsteroidal anti-inflammatory drugs and treated conservatively but continued to have transfusion-dependent anemia. Trans-arterial contrast-enhanced computed tomography showed multiple microbleeds in the small intestine.

Functional and Clinical Characterization of Variants of Uncertain Significance Identifies a Hotspot for Inactivating Missense Variants in RAD51C.

Unlabelled: Pathogenic protein-truncating variants of RAD51C, which plays an integral role in promoting DNA damage repair, increase the risk of breast and ovarian cancer. A large number of RAD51C missense variants of uncertain significance (VUS) have been identified, but the effects of the majority of these variants on RAD51C function and cancer predisposition have not been established. Here, analysis of 173 missense variants by a homology-directed repair (HDR) assay in reconstituted RAD51C-/- cells identified 30 nonfunctional (deleterious) variants, including 18 in a hotspot within the ATP-binding region.

A low prognostic nutritional index is associated with increased remote infections within 30 days of colorectal surgery: A retrospective cohort study.

Objective: This study aimed to identify risk factors for remote infection (RI) within 30 days after colorectal surgery.

Methods: This retrospective study included 660 patients who underwent colorectal surgery at Yamaguchi University Hospital or Ube Kosan Central Hospital between April 2015 and March 2019. Using electronic medical records, we identified the incidence of surgical site infection and RI within 30 days after surgery and obtained information on associated factors.

Transcatheter arterial embolization for acute lower gastrointestinal bleeding using imipenem/cilastatin: a single-center retrospective study.

Background: Transcatheter arterial embolization (TAE) is a standard treatment for acute lower gastrointestinal bleeding (LGIB) in situations where endoscopic approaches are impossible or ineffective. Various embolic materials, such as metallic coils and N-butyl cyanoacrylate, are used. This study aimed to evaluate the clinical outcomes of an imipenem/cilastatin (IPM/CS) mixture as an embolic agent in TAE for acute LGIB.

Classification of BRCA2 Variants of Uncertain Significance (VUS) Using an ACMG/AMP Model Incorporating a Homology-Directed Repair (HDR) Functional Assay.

Purpose: The identification of variants of uncertain significance (VUS) in the BRCA1 and BRCA2 genes by hereditary cancer testing poses great challenges for the clinical management of variant carriers. The ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology) variant classification framework, which incorporates multiple sources of evidence, has the potential to establish the clinical relevance of many VUS. We sought to classify the clinical relevance of 133 single-nucleotide substitution variants encoding missense variants in the DNA-binding domain (DBD) of BRCA2 by incorporating results from a validated functional assay into an ACMG/AMP-variant classification model from a hereditary cancer-testing laboratory.

Sphingomyelin maintains the cutaneous barrier via regulation of the STAT3 pathway.

Epidermal tissues play vital roles in maintaining homeostasis and preventing the dysregulation of the cutaneous barrier. Sphingomyelin (SM), a sphingolipid synthesized by sphingomyelin synthase (SMS) 1 and 2, is involved in signal transduction via modulation of lipid-raft functions. Though the implications of SMS on inflammatory diseases have been reported, its role in dermatitis has not been clarified.

Case Report: Diagnosis of Myelodysplastic Syndrome in a 72-Year-Old Female With Interstitial Lung Disease.

Acute fibrinous and organizing pneumonia (AFOP) is an entity that can be secondary to various conditions leading to lung injury, such as infections, malignancies, and various autoimmune conditions or idiopathic interstitial lung disease, when no obvious underlying cause is identified. Myelodysplastic syndromes (MDS), on the other hand, are a spectrum of clonal myeloid disorders, with a higher risk of acute leukemia, characterized by ineffective bone marrow (BM) hematopoiesis and, thus, peripheral blood (PB) cytopenias. Immune deregulation is thought to take part in the pathophysiology of the disease, including abnormal T and/or B cell responses, innate immunity, and cytokine expression.

Dietary Ceramide Prepared from Soy Sauce Lees Improves Skin Barrier Function in Hairless Mice.

Dietary sphingolipids such as glucosylceramide and sphingomyelin are known to improve the skin barrier function of damaged skin. In this study, we focused on free-ceramide prepared from soy sauce lees, which is a byproduct of soy sauce production. The effects of dietary soy sauce lees ceramide on the skin of normal mice were evaluated and compared with those of dietary maize glucosylceramide.

Lipid-soluble polyphenols from sweet potato exert antitumor activity and enhance chemosensitivity in breast cancer.

Polyphenols are abundant in vegetables and fruit. They have been shown to have various antitumor, antioxidant, and anti-inflammatory effects. Here, we extracted the lipid-soluble fraction of polyphenols from fermented sweet potato ().

Appearance of Intact Molecules of Dietary Ceramides Prepared from Soy Sauce Lees and Rice Glucosylceramides in Mouse Plasma.

Although the beneficial effects of dietary sphingolipids have recently been reported, the mechanism of their intestinal absorption has yet to be fully elucidated. In this study, the absorption and metabolism of dietary ceramides and glucosylceramides were evaluated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis in the plasma of mice after a single oral administration. Ceramide molecules prepared from soy sauce lees (mainly composed of phytosphingosine and its derivatives) were undetectable or minor compounds in the plasma of control mice but appeared 1-6 h after administration.

Condensed Film Formation and Molecular Packing in Cationic Surfactant-Cholesterol and Zwitterionic Surfactant-Cholesterol Systems at the Hexane/Water Interface.

A condensed film formation of surfactants with a charged head group at the oil/water interface was achieved by mixing surfactants of different geometric shapes to control molecular packing at the interface. The adsorbed films of mixed tetradecyltrimethylammonium bromide (C14TAB)-cholesterol (Chol) and tetradecylphosphocholine (C14PC)-Chol systems at the hexane/water interface were examined by interfacial tension and X-ray reflectivity measurements. The interfacial tension versus Chol concentration curves have break points because of the expanded-condensed phase transition of the adsorbed film.

Calculation of Liquid-Disordered/Liquid-Ordered Line Tension from Pairwise Lipid Interactions.

The energy penalty for bilayer phase domain interfaces, line tension, is an important quantity for describing the phase domain size transition from the nanometer scale to the micrometer scale and larger. We connected pairwise lipid interaction energies in ternary lipid mixtures with experimentally measured line tensions by using the compositional differences between coexisting liquid-disordered (Ld) and liquid-ordered (Lo) phases known from phase diagrams. Using a mean-field theory model, we developed a computational procedure to map out Ld + Lo phase boundaries and thermodynamic tielines based on a set of pairwise interaction energies.

Predictive value of immuno-inflammatory and nutritional measures modulated by neoadjuvant chemotherapy on the response of neoadjuvant chemotherapy and long-term outcomes in patients with esophageal cancer.

It has been reported that immuno-inflammatory and nutritional parameters are associated with long-term survival in various malignancies. However, little is known regarding the associations between alterations of these parameters during neoadjuvant chemotherapy (NAC) and the response to NAC in patients with esophageal cancer. The present study examined the clinical significance of alterations in these parameters during NAC in terms of the response to NAC and the long-term outcomes in patients with esophageal cancer.

Nutritional benefit of laparoscopic jejunostomy during neoadjuvant chemotherapy for obstructing esophageal cancer.

Neoadjuvant chemotherapy (NAC) confers a survival benefit in esophageal carcinoma, but it is difficult to perform in patients who cannot receive enteral feeding due to an esophageal obstruction. In the current study, the nutritional benefit of laparoscopic jejunostomy (Lap-J) was evaluated in patients with NAC for obstructing esophageal cancer. A total of 91 patients with esophageal cancer who received NAC between 2009 and 2017 were included in the present study.

Successful resection of a granulocyte colony-stimulating factor-producing carcinoma of the pancreas: A case report.

Granulocyte colony-stimulating factor (G-CSF) is a naturally occurring glycoprotein that stimulates the proliferation of precursor cells in the bone marrow and their maturation into fully differentiated neutrophils. G-CSF-producing cancers rarely occur in the digestive system, particularly the pancreas. Herein we report the rare case of a G-CSF-producing pancreatic carcinoma associated with severe anemia due to bleeding in the duodenum, which was successfully treated with surgery.

Evaluation of BacterioScan 216Dx in Comparison to Urinalysis as a Screening Tool for Diagnosis of Urinary Tract Infections in Children.

Urinalysis (UA) has routinely been used as a screening tool prior to urine culture set up. BacterioScan 216Dx is an FDA-cleared semiautomated system to detect bacterial growth in urine. The aim of this study was to evaluate 216Dx in comparison to UA for diagnosis of urinary tract infection (UTI) in children.

Long-term outcome following sentinel node navigation surgery for cT1 gastric cancer.

Sentinel node navigation surgery (SNNS) has become a standard procedure for early-stage melanoma and breast cancer. However, very few studies have evaluated the long-term clinical outcomes following SNNS for gastric cancer. The present study analyzed 51 patients with cT1 gastric cancer who underwent SNNS at our hospital.