Multi-shelled ECIF: improved extended connectivity interaction features for accurate binding affinity prediction.

Motivation: Extended connectivity interaction features (ECIF) is a method developed to predict protein-ligand binding affinity, allowing for detailed atomic representation. It performed very well in terms of Comparative Assessment of Scoring Functions 2016 (CASF-2016) scoring power. However, ECIF has the limitation of not being able to adequately account for interatomic distances. Results: To investigate what kind of distance representation is effective for P-L binding affinity prediction, we have developed two algorithms that improved ECIF's feature extraction method to take distance into account. One is multi-shelled ECIF, which takes into account the distance between atoms by dividing the distance between atoms into multiple layers. The other is weighted ECIF, which weights the importance of interactions according to the distance between atoms. A comparison of these two methods shows that multi-shelled ECIF outperforms weighted ECIF and the original ECIF, achieving a CASF-2016 scoring power Pearson correlation coefficient of 0.877. Availability and implementation: All the codes and data are available on GitHub (https://github.com/koji11235/MSECIFv2).

AQDnet: Deep Neural Network for Protein-Ligand Docking Simulation.

We have developed an innovative system, AI QM Docking Net (AQDnet), which utilizes the three-dimensional structure of protein-ligand complexes to predict binding affinity. This system is novel in two respects: first, it significantly expands the training dataset by generating thousands of diverse ligand configurations for each protein-ligand complex and subsequently determining the binding energy of each configuration through quantum computation. Second, we have devised a method that incorporates the atom-centered symmetry function (ACSF), highly effective in describing molecular energies, for the prediction of protein-ligand interactions. These advancements have enabled us to effectively train a neural network to learn the protein-ligand quantum energy landscape (P-L QEL). Consequently, we have achieved a 92.6% top 1 success rate in the CASF-2016 docking power, placing first among all models assessed in the CASF-2016, thus demonstrating the exceptional docking performance of our model.

[A Case Report of Neuroendocrine Carcinoma in the Gall Bladder Showing Recurrence Shortly after Surgery].

A55 -year-old woman with a 10×8mm protuberant gallbladder lesion visited our hospital. To determine possible malignancy, she underwent laparoscopic excision biopsy of the gallbladder, and pathological findings revealed an endocrine carcinoma in the gallbladder. Surgery involved extrahepatic bile duct resection, gallbladder bed resection, and hepatic portal lymph node resection. Recurrence in the peritoneal lymph node was observed in the early postoperative period. Chemotherapy was initiated with cisplatin and irinotecan, and continues 18 months post-operatively. Neuroendocrine carcinoma of the gallbladder is rare and is known to have a poor prognosis, with few confirmed treatments reported for this disease due to its rarity. Therefore, we report this case along with a review of the literature.

Probe-Based Confocal Laser Endomicroscopy Using Acrinol as a Novel Dye Can Be Used to Observe Cancer Nuclei of Bladder Carcinoma In Situ.

Background: Cystoscopy using white light is a standard procedure for diagnosing bladder cancer; however, white light can result in missed lesions that are present, but not visible, such as in cases of carcinoma in situ (CIS). In this case report, we describe observing the nuclei of urothelial carcinoma cells in situ that were not visible with cystoscopy under white light using probe-based confocal laser endomicroscopy (pCLE) with acrinol and fluorescein during transurethral resection of a bladder tumor (TURBT). Case Presentation: A 59-year-old male with a medical history of neurogenic bladder dysfunction with multiple bladder diverticula was referred to the urology department for gross hematuria. TURBT was performed with the assistance of pCLE, using acrinol as a novel dye. Standard cystoscopy under white light could not detect any bladder tumor; however, pCLE using acrinol could detect the abnormal nuclei of bladder CIS. Subsequent histopathologic analysis of the specimen confirmed a diagnosis of bladder CIS. To our knowledge, this is the first reported case of bladder CIS diagnosed with the assistance of pCLE using acrinol in a patient undergoing a TURBT. Conclusion: pCLE using acrinol as a novel dye can help observe the cancerous nuclei of bladder CIS that cannot be detected using conventional cystoscopy under white light. Therefore, pCLE using acrinol is one possible modality for performing an optical biopsy during TURBT.

[Laparoscopic radiofrequency ablation for hepatocellular carcinoma].

We examined the case of laparoscopic radiofrequency ablation (L-RFA) to hepatocellular carcinoma (HCC), and then the method of this treatment was considered in terms of selection and adjustment. Between January 2008 and May 2010, L-RFC was performed on 18 cases (27 tumors). A total operation time was 203 minutes (± 85.5). The median survival time was 562 days (± 197 day). The amount of blood was 21.0 g (± 68.4), and 3 postoperative complications (pleural effusion) were observed. The average length of hospital stay after the operation was 8 days. There was no vestigial remnant in all cases after the operation. The prognosis of death due to a liver failure was one case on the 516th day after the operation. All other 17 cases were survived. If the tumors were identified by the naked eye and ultrasonography, and considering the position in relation to the main vas, the ablation would be possible for the troublesome part in case of the percutaneous approach. Therefore, we thought the application of RFA to HCC would be more expandable.

Pancreatic acinar cell carcinoma extending into the common bile and main pancreatic ducts.

Acinar cell carcinoma (ACC) of the pancreas is relatively rare, accounting for only approximately 1% of all exocrine pancreatic tumors. A 69-year-old man was found to have a mass lesion measuring approximately 4 cm in diameter in the pancreatic head on ultrasound, abdominal dynamic CT, and percutaneous transhepatic cholangiography. Magnetic resonance cholangiopancreatography showed defect of the lower common bile duct (CBD) due to obstruction by the tumor cast. Histopathologically, the pancreatic head tumor invaded the main pancreatic duct (MPD) and CBD with extension into the CBD in a form of tumor cast. The tumor cells consisted of a solid proliferation with abundant eosinophilic cytoplasm and round nuclei in an acinar and trabecular fashion. A 55-year-old man with upper abdominal pain and nausea, had a cystic lesion approximately 3 cm in size in the pancreatic tail on CT. Histopathologically, the tumor was encapsulated by fibrous capsule and had extensive central necrosis with solid areas in the tumor periphery, and invaded with extension into the MPD in a form of tumor cast. The tumor cells resembled acinar cells in solid growths. Two resected cases of ACC with unusual tumor extension into the CBD and the MPD, respectively, are reported.

Carcinoid tumor of the Vater's papilla presenting with chronic pancreatitis--a case report--.

Carcinoid tumors are common in the duodenum except for in the Vater's papilla [1-9]. We report here a case of carcinoid tumor arising in the Vater's papilla with repeated episods of pancreatitis. The patient is a 28 year-old-woman who had repeated abdominal pain with elevated serum amylase and had been treated as chronic pancreatitis. Computed tomography (CT) revealed a slight dilatation of the main pancreatic duct from the pancreatic head to the tail, and mild swelling of the pancreas. A submucosal tumor measuring 1.3 cm in diameter was detected in the ampulla of Vater by esophagogastroduodenscopy (EGD), and total papillectomy was performed under the suspicious of carcinoid tumor. The tumor was not encapsulated, 1.0 cm in diameter, undefined, and whitish in color. Histologically monomorphic tumor cells with lightly eosinophlic cytoplasm and round nuclei proliferate in trabecular and solid patterns. Immunohistochemically tumor cells were positive for neuron-specific enolase, chromogranin A and synaptophysin, and the tumor was diagnosed as carcinoid tumor. It should be noted that carcinoid tumor in the ampulla may occur with initial signs of acute or chronic pancreatitis.

The pathogenesis of nonalcoholic steatohepatitis and other fatty liver diseases: a four-step model including the role of lipid release and hepatic venular obstruction in the progression to cirrhosis.

Fatty liver disease involves the accumulation of triglycerides in hepatocytes, necrosis of hepatocytes, inflammation, and often fibrosis with progression to cirrhosis. The two-hit model summarizes the important early metabolic events leading to hepatocellular necrosis in nonalcoholic steatohepatitis (NASH). In this article, we provide evidence of lipid release from hepatocytes in posttransplant fat necrosis and in NASH and quantify vascular obliteration in a series of biopsies with NASH. Obliteration of small hepatic veins (<30 microm) in small numbers is compensated by collateral flow. Obliteration of larger hepatic veins (>30 microm) is associated with fibrotic collapse lesions that are not easily resorbed. Based on these observations, we propose a new four-step model that includes the later events that lead to cirrhosis after necrosis has occurred. This model is applicable to nonalcoholic fatty liver disease (NAFLD), alcoholic disease, postjejunoileal bypass disease, and posttransplant fat necrosis. The first step is steatosis facilitated by insulin, and the second is necrosis induced by intracellular lipid toxicity or lipid peroxidation, or both, modified by alcohol, drugs, and ischemia. The third step is release of bulk lipid from hepatocytes into the interstitium leading to direct and inflammatory injury to hepatic veins. The fourth step is venous obstruction with secondary collapse and ultimately fibrous septation and cirrhosis.

Ramipril-associated hepatotoxicity.

CONTEXT: Angiotensin-converting enzyme inhibitors are prescribed for many cardiovascular and renal diseases. Adverse hepatic events, especially cholestasis, have rarely been reported with captopril, enalapril, lisinopril, and fosinopril. To date, hepatic injury associated with ramipril has not been reported. OBJECTIVE: To describe 3 patients who developed hepatitis, with or without jaundice, after receiving ramipril. DESIGN: Medical records and liver biopsies of the 3 patients were reviewed. Clinical, laboratory, and histologic findings were compared with findings in other cases of angiotensin-converting enzyme inhibitor-induced liver injury reported in the literature. RESULTS: The 3 patients were middle-aged men. In 2 patients, jaundice appeared 4 and 8 weeks after starting ramipril. Bilirubin levels peaked at 15.5 and 5 mg/dL, and alkaline phosphatase values peaked at 957 and 507 U/L. Aminotransferase levels were mildly elevated. Endoscopic retrograde cholangiopancreatography and ultrasonography showed no bile duct obstruction. Liver biopsies from the jaundiced patients were similar, with cholestasis, duct necrosis, and extravasation of bile, ductular proliferation, and portal inflammation. Cholestasis improved in 1 patient 6 weeks after stopping ramipril and was prolonged for 14 months in the other, in whom biliary cirrhosis was present on biopsy. The third patient developed hepatitis without jaundice 3 weeks after starting ramipril; symptoms resolved after stopping the drug. Ramipril-associated liver injury is similar to that seen with other angiotensin-converting enzyme inhibitors, but liver biopsy findings of duct necrosis and extravasation of bile have not been reported previously. CONCLUSION: Prolonged cholestatic hepatitis and biliary cirrhosis may result from the use of ramipril. Monitoring of liver enzymes is advisable for patients starting on ramipril.