Deaminase-mediated chromatin accessibility profiling with single-allele resolution.

Binding of transcription factors (TFs) at gene regulatory elements controls cellular epigenetic state and gene expression. Current genome-wide chromatin profiling approaches have inherently limited resolution, complicating assessment of TF occupancy and co-occupancy, especially at individual alleles. In this work, we introduce Accessible Chromatin by Cytosine Editing Site Sequencing with ATAC-seq (ACCESS-ATAC), which harnesses a double-stranded DNA cytosine deaminase (Ddd) enzyme to stencil TF binding locations within accessible chromatin regions.

Solitary fibrous tumor of the gallbladder: a case report.

Background: Primary solitary fibrous tumors (SFTs) of the gallbladder are rare. Here, we report the case of a patient who underwent surgical treatment for a primary SFT originating in the gallbladder.

Case Presentation: A 48-mm gallbladder tumor was detected in a 70-year-old man using abdominal ultrasonography at a primary hospital, and he was subsequently referred to our department.

Dynamic regulation of inter-organelle communication by ubiquitylation controls skeletal muscle development and disease onset.

Ubiquitin-proteasome system (UPS) dysfunction is associated with the pathology of a wide range of human diseases, including myopathies and muscular atrophy. However, the mechanistic understanding of specific components of the regulation of protein turnover during development and disease progression in skeletal muscle is unclear. Mutations in , an E3 ubiquitin ligase cullin3 (CUL3) substrate-specific adapter protein, result in severe congenital nemaline myopathy, but the events that initiate the pathology and the mechanism through which it becomes pervasive remain poorly understood.

Dynamics of the prognostic nutritional index in preoperative chemotherapy in patients with colorectal liver metastases.

Background: Identifying the prognostic indicators that reflect the efficacy of preoperative chemotherapy is necessary. In this study, we investigated the prognostic indicators targeting the systemic inflammatory response for the administration of preoperative chemotherapy in patients with colorectal liver metastases.

Methods: Data for 192 patients were retrospectively analyzed.

Semisynthetic Approach to the Analysis of Tumor Suppressor PTEN Ubiquitination.

Phosphatase and tensin homologue (PTEN) tumor suppressor protein is a PIP3 lipid phosphatase that is subject to multifaceted post-translational modifications. One such modification is the monoubiquitination of Lys13 that may alter its cellular localization but is also positioned in a manner that could influence several of its cellular functions. To explore the regulatory influence of ubiquitin on PTEN's biochemical properties and its interaction with ubiquitin ligases and a deubiquitinase, the generation of a site-specifically and stoichiometrically ubiquitinated protein could be beneficial.

Successful resection of port site recurrence of pancreatic ductal adenocarcinoma after laparoscopic distal pancreatectomy.

Background: There are many reports of port site recurrence after laparoscopic surgery for various types of cancer. However, only two cases of port site recurrence after laparoscopic pancreatectomy have been reported to date. We herein report a case of port site recurrence after laparoscopic distal pancreatectomy.

D1 Distal Pancreatectomy for Left-sided Pancreatic Ductal Adenocarcinoma Is Justifiable: A Propensity-score Matched Multicenter Study.

Background/aim: Evidence on the optimal extent of lymph node dissection for left-sided pancreatic ductal adenocarcinoma (PDAC) is scarce. The aim of the current study was to compare the long-term outcomes of patients who underwent D1 distal pancreatectomy (DP) with D2 DP for left-sided PDAC.

Patients And Methods: Patients undergoing DP for left-sided PDAC at the four institutions affiliated to The Jikei University were enrolled in this study.

The structural basis of PTEN regulation by multi-site phosphorylation.

Phosphatase and tensin homolog (PTEN) is a phosphatidylinositol-3,4,5-triphosphate (PIP) phospholipid phosphatase that is commonly mutated or silenced in cancer. PTEN's catalytic activity, cellular membrane localization and stability are orchestrated by a cluster of C-terminal phosphorylation (phospho-C-tail) events on Ser380, Thr382, Thr383 and Ser385, but the molecular details of this multi-faceted regulation have remained uncertain. Here we use a combination of protein semisynthesis, biochemical analysis, NMR, X-ray crystallography and computational simulations on human PTEN and its sea squirt homolog, VSP, to obtain a detailed picture of how the phospho-C-tail forms a belt around the C2 and phosphatase domains of PTEN.

Identification of Functional Domains of CXCL14 Involved in High-Affinity Binding and Intracellular Transport of CpG DNA.

Some CXC chemokines, including CXCL14, transport CpG oligodeoxynucleotides (ODNs) into dendritic cells (DCs), thereby activating TLR9. The molecular basis of this noncanonical function of CXC chemokines is not well understood. In this study, we investigated the CpG ODN binding and intracellular transport activities of various CXC chemokines and partial peptides of CXCL14 in mouse bone marrow-derived dendritic cells.

Ischemic small bowel perforation caused by cholesterol crystal embolism following transcatheter arterial chemoembolization for recurrent hepatocellular carcinoma: a case report.

Background: Cholesterol crystal embolism (CCE) following transcatheter arterial chemoembolization (TACE) is rare.

Case Presentation: A 71-year-old man underwent TACE for recurrence of hepatocellular carcinoma (HCC). On postoperative day (POD) 5, he developed abdominal pain and fever.

Clinically based score predicting cryptogenic NORSE at the early stage of status epilepticus.

Objective: To determine whether a clinically based score predicts cryptogenic new-onset refractory status epilepticus (C-NORSE) at the early stage of status epilepticus (SE) with prominent motor symptoms (SE-M) of unclear etiology.

Methods: The score (range 0-6) included 6 clinical features: highly refractoriness to antiseizure drugs, previously healthy individual, presence of prodromal fever, absence of prodromal psychobehavioral or memory alterations, absence of dyskinesias, and symmetric brain MRI abnormalities (the first 2 mandatory). We retrospectively assessed the usefulness of a high scale score (≥5) in predicting C-NORSE in 83 patients with SE-M of unclear etiology, who underwent testing for neuronal surface antibodies (NS-Abs) between January 2007, and December 2019.

Intracranial dural arteriovenous fistula mimicking neuromyelitis optica spectrum disorder: A case report.

Neuromyelitis optica spectrum disorder (NMOSD) is an immune-mediated disorder. It often develops acute myelopathy due to longitudinally extensive transverse myelitis (LETM), although other disorders can cause an LETM-like lesion. Here, we report a 76-year-old patient presenting with acute-onset, progressive myelopathy, which proved to be caused by an intracranial dural arteriovenus fistula (dAVF).

Dupilumab for Atopic Dermatitis, a Possible Risk Factor of Juvenile Ischemic Stroke: A Case Report.

Dupilumab, a dual inhibitor of IL-4 and IL-13 cytokine signaling, is indicated for the treatment of moderate-to-severe atopic dermatitis, which leads to the control of atopic dermatitis. The cytokines IL-4 and IL-13 are related to vascular inflammation, which is mediated by vascular endothelial cells. We report the case of a 20-year-old man with atopic dermatitis treated with dupilumab for half a year, who presented with sudden onset of dizziness, nausea, and slight cerebellar ataxia.

Interaction Energetics and Druggability of the Protein-Protein Interaction between Kelch-like ECH-Associated Protein 1 (KEAP1) and Nuclear Factor Erythroid 2 Like 2 (Nrf2).

Development of small molecule inhibitors of protein-protein interactions (PPIs) is hampered by our poor understanding of the druggability of PPI target sites. Here, we describe the combined application of alanine-scanning mutagenesis, fragment screening, and FTMap computational hot spot mapping to evaluate the energetics and druggability of the highly charged PPI interface between Kelch-like ECH-associated protein 1 (KEAP1) and nuclear factor erythroid 2 like 2 (Nrf2), an important drug target. FTMap identifies four binding energy hot spots at the active site.

Assessment of Outcome of Hepatic Resection for Extremely Elderly Patients With a Hepatic Malignancy.

Background/aim: We aimed to assess surgical outcome and long-term survival after elective hepatic resection for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) in patients aged 80 years or older.

Patients And Methods: This study included 100 patients aged 70 years or older, who underwent hepatic resection for HCC or CRLM between January 2000 and December 2012. Outcomes and clinicopathological data were compared between the elderly (aged 70-79 years; n=84) and extremely elderly groups (aged 80 years or older; n=16).

Risk Factors for Deterioration of Remnant Liver Function After Hepatic Resection for Hepatocellular Carcinoma.

Background/aim: After primary resection of hepatocellular carcinoma (HCC), the impact of patient's characteristics at the initial hepatectomy, on long-term remnant liver function has not been reported. The aim of this study was to identify factors associated with the deterioration of remnant liver function among patients who developed recurrent HCC.

Patients And Methods: A total of 51 patients with intrahepatic recurrence after initial hepatic resection for HCC were included.

Assessment of Outcome of Hepatic Resection for Extremely Elderly Patients With a Hepatic Malignancy.

Background/aim: We aimed to assess surgical outcome and long-term survival after elective hepatic resection for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) in patients aged 80 years or older.

Patients And Methods: This study included 100 patients aged 70 years or older, who underwent hepatic resection for HCC or CRLM between January 2000 and December 2012. Outcomes and clinicopathological data were compared between the elderly (aged 70-79 years; n=84) and extremely elderly groups (aged 80 years or over; n=16).

Double Percutaneous Transesophageal Gastrotubing for Gastric Cancer: A Pilot Study.

Background: The management of gastric cancer causing gastric outlet obstruction and dilatation must include decompression of the stomach and intravenous nutrition. Percutaneous transesophageal gastrotubing (PTEG) is an effective technique for either gastric decompression or enteral nutrition. Here, we investigated the efficacy and safety of double PTEG (dPTEG), that is, using PTEG for both purposes simultaneously, in patients with gastric cancer.

Glycogen synthase kinase-3β activity plays a key role in the antitumor effect of nafamostat mesilate in pancreatic cancer cells.

Pancreatic cancer is often resistant to chemotherapy. We previously showed the efficacy of combination treatment using gemcitabine and nafamostat mesilate (FUT-175) for patients with unresectable pancreatic cancer. However, the mechanisms that affect the sensitivity of FUT-175 are not fully understood.

Pomalidomide promotes chemosensitization of pancreatic cancer by inhibition of NF-κB.

Introduction: Nuclear factor κB (NF-κB) plays an important role in cancer progression and causes therapeutic resistance to chemotherapy. Pomalidomide, a third-generation immunomodulating drug derived from thalidomide, has been approved for uncontrolled multiple myeloma. We hypothesized that pomalidomide may inhibit the anticancer agent-induced NF-κB activity and enhance chemosensitization of combination chemotherapy with gemcitabine and S1 (Gem/S1) in pancreatic cancer.

Optimal timing of preoperative indocyanine green administration for fluorescent cholangiography during laparoscopic cholecystectomy using the PINPOINT® Endoscopic Fluorescence Imaging System.

Introduction: The PINPOINT® Endoscopic Fluorescence Imaging System (Novadaq, Mississauga, Canada) allows surgeons to visualize the bile ducts during laparoscopic cholecystectomy. Surgeons can continue operation while confirming the bile ducts' fluorescence with a bright-field/color image. However, strong fluorescence of the liver can interfere with the surgery.

OsCERK1 plays a crucial role in the lipopolysaccharide-induced immune response of rice.

Plant cell surface receptor-like kinases (RLKs) mediate the signals from microbe-associated molecular patterns (MAMPs) that induce immune responses. Lipopolysaccharide (LPS), the major constituent of the outer membrane of gram-negative bacteria, is a common MAMP perceived by animals and plants; however, the plant receptors/co-receptors are unknown except for LORE, a bulb-type lectin S-domain RLK (B-lectin SD1-RLK) in Arabidopsis. OsCERK1 is a multifunctional RLK in rice that contains lysin motifs (LysMs) and is essential for the perception of chitin, a fungal MAMP, and peptidoglycan, a bacterial MAMP.

Training of Intra-Axial Brain Tumor Resection Using a Self-Made Simple Device with Agar and Gelatin.

Introduction: Self-made devices composed of agar and gelatin gel were used for resident training in intra-axial brain tumor resection. The mixture gel of agar and gelatin is retractable and can be suctioned. Hardness of the gel depends on the concentration of the solution.