Safe model based optimization balancing exploration and reliability for protein sequence design.

Discovering proteins with desired functionalities using protein engineering is time-consuming. Offline Model-Based Optimization (MBO) accelerates protein sequence design by exploring the vast protein sequence space using a trained proxy model. However, the proxy model often yields excessively good values that are far from the training dataset and causes pathological behavior in the MBO.

Functional Outcomes after Subtotal/Total Glossectomy with Microsurgical Reconstruction: A Multicenter Prospective Observational Study in Japan.

Background: This prospective observational multicenter study aimed to provide evidence-based data on the risk factors for feeding tube dependence, oral intake level, and speech function after tongue reconstruction.

Patients And Methods: This study was conducted by the Oral Pharyngeal Esophageal Operation and Reconstruction Analytical group across 21 Japanese institutions. Patients with oral tongue squamous cell carcinoma who underwent microsurgical reconstruction following subtotal/total glossectomy were included.

Phase II study of afatinib for advanced non-small cell lung cancer with uncommon epidermal growth factor receptor mutations, including compound mutations detected by next-generation sequencing.

Background: There are no prospective clinical data on the efficacy of afatinib in patients with non-small cell lung cancer (NSCLC) harboring various uncommon epidermal growth factor receptor (EGFR) mutations detected using next-generation sequencing. We aimed to report the efficacy and safety of afatinib in patients with NSCLC harboring uncommon EGFR mutations detected using next-generation sequencing.

Methods: This was a prospective single-center single-arm phase II study.

A prospective, randomized, double-blind, placebo-controlled trial of the Kampo formula daiobotanpito combined with antibiotic therapy for acute diverticulitis.

Daiobotanpito (DBT) is a Kampo formula traditionally used to treat abscesses in intestinal disorders. This double-blind, multicenter, randomized controlled trial was conducted at participating hospitals in Japan. Patients with CT-proven moderate acute diverticulitis received conventional therapy along with an oral DBT (treatment group) or placebo (control group) administered thrice a day for 10 days (Registration: jRCTs041180063).

Metal-Responsive Up-Regulation of Bifunctional Disulfides for Suppressing Protein Misfolding and Promoting Oxidative Folding.

The stress-responsive up-regulation process is a sophisticated biological response to maintain cellular homeostasis. In intracellular anti-oxidant systems, the expression level of oxidoreductases is up-regulated under oxidative stress, mitigating oxidative damage on biomolecules and enhancing protein folding capacity. Herein, inspired by the biological system, we developed a synthetic folding promotor whose reactivity is up-regulated under stress conditions.

A Randomized Trial of Nutrition and Exercise Treatment in Patients With Pancreatic and Non-Small Cell Lung Cancer (NEXTAC-TWO).

Background: In our previous study (NEXTAC-ONE), the Nutrition and Exercise Treatment for Advanced Cancer (NEXTAC) program (including home-based exercise and branched-chain amino acid-containing supplements combined with nutritional counselling) was shown to potentially prevent low muscle mass-related disability in elderly cancer patients. This randomized controlled trial (NEXTAC-TWO) was conducted to elucidate whether the NEXTAC program prolongs disability-free survival in elderly patients with advanced pancreatic or non-small cell lung cancer.

Methods: This open-label, multicentre, randomized phase II study was conducted at 15 Japanese hospitals.

A randomized, double-blind, placebo-controlled phase III study evaluating the preventive effect of diclofenac cream on capecitabine-related hand-foot syndrome: study protocol of J-SUPPORT2401/JORTC-SUP06 (J-DIRECT).

Background: Clinical evidence on preventive therapy for capecitabine-induced hand-foot syndrome (HFS) is limited, and moisturizing and avoiding local pressure are recommended in guidelines. Although the precise pathogenesis and mechanisms of HFS remain unclear, inflammatory reactions are thought to be involved. The preventive effects of topical diclofenac gel have been reported from India.

Correlation between cancer cachexia and psychosocial impact in older patients with advanced lung cancer undergoing chemotherapy.

Objective: This study aimed to evaluate the association of cancer cachexia with psychosocial impact, nutrition impact symptoms (NIS), and geriatric assessment in older patients newly diagnosed with advanced lung cancer undergoing chemotherapy.

Methods: Older patients with advanced lung cancer scheduled to receive first-line chemotherapy between August 2021 and February 2022 were enrolled. Cachexia was diagnosed according to the International Consensus.

Activity and safety of atezolizumab plus carboplatin and paclitaxel in patients with advanced or recurrent thymic carcinoma (MARBLE): a multicentre, single-arm, phase 2 trial.

Background: Despite the poor prognosis of advanced or recurrent thymic carcinoma, the rarity of thymic carcinoma has delayed the development and introduction of novel pharmacotherapy options. Carboplatin plus paclitaxel remains a standard treatment for chemotherapy-naive advanced or recurrent thymic carcinoma. We evaluated the activity and safety of atezolizumab combined with chemotherapy.

Assessment of safety and patency of 7-mm covered metal stents for preoperative biliary drainage in pancreatic cancer: Prospective multicenter study.

Background And Study Aims: For preoperative biliary drainage of pancreatic cancer (PC), a 10-mm diameter metal stent (MS) is commonly used; however, the rate of pancreatitis is high. It is hypothesized that smaller-diameter MS may reduce the rate of pancreatitis. Therefore, we conducted a multicenter prospective study to evaluate the efficacy and safety of 7-mm MS.

Outcomes of thoracic endovascular aortic repair for complicated type B acute aortic dissection from a multicenter Japanese post-market surveillance study.

Objectives: A primary goal of thoracic endovascular aortic repair (TEVAR) for type B acute aortic dissection (BAAD) is exclusion of the primary entry tear with a suitable stent graft (SG) to reestablish true lumen flow and promote aortic remodeling. This study aimed to determine the safety and efficacy of a conformable thoracic SG in a Japanese population with complicated BAAD.

Methods: Between 2016 and 2017, 43 patients with complicated BAAD were enrolled in this prospective, nonrandomized, multicenter post-market surveillance study at 27 sites in Japan.

Prospective randomized trial of antibiotic prophylaxis for percutaneous renal biopsy.

Background: Infection is a rare complication of percutaneous renal biopsy (RB). However, the questionnaire included in the Kidney Biopsy Guidebook 2020 in Japan revealed that antibiotic prophylaxis (AP) was administered at about 60% of hospitals. The objective of this study was to evaluate whether it is possible to omit AP for RB.

A phase II study of ME2136 (Asenapine Maleate) plus standard antiemetic therapy for patients, including diabetic patients, receiving cisplatin-based chemotherapy.

Olanzapine combined with the neurokinin-1 receptor antagonist, palonosetron and dexamethasone is the standard treatment for chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC). However, the use of olanzapine poses challenges in patients with diabetes mellitus (DM) due to the potential risk of hyperglycemia. ME2136, antipsychotic similar to olanzapine, is associated with a lower risk of hyperglycemia.

Final Analysis Data and Exploratory Biomarker Analysis of a Randomized Phase 2 Study of Osimertinib Plus Bevacizumab Versus Osimertinib Monotherapy for Untreated Patients With Nonsquamous NSCLC Harboring EGFR Mutations: The WJOG9717L Study.

Introduction: EGFR tyrosine kinase inhibitors have been the standard treatment for patients with NSCLC who have sensitive mutations. This study revealed final analysis survival data, biomarkers, and resistance mechanisms of osimertinib plus bevacizumab or osimertinib monotherapy in previously untreated patients with advanced -positive nonsquamous NSCLC.

Methods: We previously reported the primary results of a randomized, open-label, phase 2 study comparing osimertinib plus bevacizumab with osimertinib monotherapy for this population.

Deletion of p38 MAPK in macrophages ameliorates peritoneal fibrosis and inflammation in peritoneal dialysis.

One of the most common causes of peritoneal dialysis withdrawal is ultrafiltration failure which is characterized by peritoneal membrane thickening and fibrosis. Although previous studies have demonstrated the inhibitory effect of p38 MAPK inhibitors on peritoneal fibrosis in mice, it was unclear which specific cells contribute to peritoneal fibrosis. To investigate the role of p38 MAPK in peritoneal fibrosis more precisely, we examined the expression of p38 MAPK in human peritoneum and generated systemic inducible p38 MAPK knockout mice and macrophage-specific p38 MAPK knockout mice.

Safety and efficacy of underwater EMR for 10- to 20-mm colorectal serrated lesions (SEA CLEAR study).

Background And Aims: Colorectal serrated lesions (SLs) are precursors of colorectal carcinoma via the serrated neoplasia pathway. However, the success rate of endoscopic resection of large SLs is low. Therefore, this study aimed to determine the safety and efficacy of underwater EMR (UEMR) for SLs sized 10 to 20 mm.

Daily change of peritoneal ultrafiltration volume in patients with hybrid dialysis.

Introduction: Hybrid dialysis is widely used in Japan. Although previous reports have shown the beneficial effects of hybrid dialysis, little is known about the daily change in peritoneal ultrafiltration volume in hybrid dialysis.

Methods: A multicenter, cross-sectional study was conducted in 25 patients with hybrid dialysis.

Trial Protocol of a Phase II Study of mFOLFOXIRI after Metastasectomy in Patients with Oligometastatic Colorectal Cancer (FANTASTIC Study).

Background: The survival benefit of adjuvant chemotherapy after surgical resection of oligometastases from colorectal cancer (CRC) remains unclear. The prognostic role of circulating-tumor DNA (ctDNA) was reported recently and a risk stratification strategy based on monitoring minimal/molecular residual disease (MRD) has been proposed, however, which drug regimen is most effective for ctDNA-positive patients is unknown.

Methods/design: Oligometastatic CRC patients planning to undergo surgery were registered in this study.

Association between recovery from desaturation after stair climbing and postoperative complications in lung resection.

Objective: The stair-climbing test (SCT) is used as a surrogate for cardiopulmonary exercise testing, which measures maximal oxygen uptake, and considered a useful method for assessing exercise capacity in thoracic surgery. This study aims to investigate whether the recovery time of percutaneous oxygen saturation (SpO) after stair climbing is a predictor of postoperative complications after lobectomy.

Methods: We retrospectively identified 54 patients who performed SCT and underwent lobectomy between January 2015 and February 2023 at Shizuoka Cancer Center.

Proton and carbon ion radiotherapy for operable early-stage lung cancer; a prospective nationwide registry.

Background And Purpose: To investigate the toxicity and survival outcomes of proton and carbon ion radiotherapy for patients with operable early-stage lung cancer who are eligible for lobectomy.

Materials And Methods: This multicenter nationwide prospective cohort study included patients with operable early-stage lung cancer. Proton and carbon ion radiotherapy was performed according to the schedule stipulated in the unified treatment policy.

Shared decision-making support program for older patients with advanced cancer using a question prompt list and geriatric assessment: A pilot randomized controlled trial.

Introduction: Older patients with cancer are less likely to express their treatment preferences than younger patients. Question prompt lists (QPLs) facilitate communication between patients and physicians. Geriatric assessment (GA) is recommended when older patients with cancer make treatment decisions.

Monitoring ctDNA RAS Mutational Status in Metastatic Colorectal Cancer: A Trial Protocol of RAS-trace and RAS-trace-2 Studies.

Background: Spatial and temporal heterogeneities of RAS and other molecular genes should be considered in the treatment of metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs); acquired RAS mutation is sometimes observed at disease progression of treatment with the anti-EGFR mAb. At the same time, discrepancy of RAS status from tissues and circulating tumor DNA (ctDNA) in the same patient is sometimes observed. Based on this, we commenced two observational studies to clarify these heterogeneities of RAS and BRAF in mCRC, using next generation sequencing from liquid biopsy.

Diagnostic performance of linked color imaging for gastric cancer by Helicobacter pylori infection status: A subanalysis of the large-scale, multicenter randomized controlled trial LCI-FIND.

Background: Linked color imaging (LCI) is a new image enhancement technology that facilitates the recognition of subtle differences in mucosal color. In the large-scale, multicenter randomized controlled trial LCI-FIND, LCI demonstrated good diagnostic performance for the detection of tumor lesions in the upper gastrointestinal tract. The aim of the present study was to exploratively evaluate the diagnostic performance of LCI according to H.