Unifying community-wide whole-brain imaging datasets enables robust automated neuron identification and reveals determinants of neuron positioning in C. elegans.

We develop a data harmonization approach for C. elegans volumetric microscopy data, still or video, consisting of a standardized format, data pre-processing techniques, and a set of human-in-the-loop machine learning based analysis software tools. We unify a diverse collection of 118 whole-brain neural activity imaging datasets from 5 labs, storing these and accompanying tools in an online repository called WormID ( wormid.org ). We use this repository to generate a statistical atlas that, for the first time, enables accurate automated cellular identification that generalizes across labs, approaching human performance in some cases. We mine this repository to identify factors that influence the developmental positioning of neurons. To facilitate communal use of this repository, we created open-source software, code, web-based tools, and tutorials to explore and curate datasets for contribution to the scientific community. This repository provides a growing resource for experimentalists, theorists, and toolmakers to investigate neuroanatomical organization and neural activity across diverse experimental paradigms, develop and benchmark algorithms for automated neuron detection, segmentation, cell identification, tracking, and activity extraction, and inform models of neurobiological development and function.

PYloroplasty versus No Intervention in GAstric REmnant REconstruction after Oesophagectomy: study protocol for the PYNI-GAREREO phase III randomized controlled trial.

BACKGROUND: After esophagectomy for esophageal and esophagogastric cancer, more than half of patients have lost > 10% of their body weight at 12 months. In most cases, the gastric remnant is used for reconstruction after esophagectomy. One of the most serious nutritional complications of this technique is delayed gastric emptying caused by gastric remnant mobilization and denervation of the vagus nerve. The aim of the PYloroplasty versus No Intervention in GAstric REmnant REconstruction after Oesophagectomy (PYNI-GAREREO) trial is to analyze the clinical outcome of modified Horsley pyloroplasty (mH-P) as a method of preventing delayed gastric emptying. METHODS: The PYNI-GAREREO trial is designed as an open randomized, single-center superiority trial. Patients will be randomly allocated to undergo gastric remnant reconstruction with mH-P (intervention group) or no intervention (control group) in parallel groups. All patients with esophageal cancer or esophagogastric cancer planning to undergo curative minimally invasive esophagectomy will be considered for inclusion. A total of 140 patients will be included in the study and randomized between the groups in a 1:1 ratio. The primary outcome is the body weight change at 6 months postoperatively, and the secondary outcomes are the nutritional status, postoperative complications, functional outcome, and quality of life until 1 year postoperatively. DISCUSSION: We hypothesize that mH-P after minimally invasive esophagectomy more effectively maintains patients' nutritional status than no pyloroplasty. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000045104. Registered on 25 August 2021. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000051346 .

Initial Results of Laparoscopic Proximal Gastrectomy With Double-tract Reconstruction Using Oblique Jejunogastrostomy Method on the Long-term Outcome of Postoperative Nutritional Status: A Propensity Score-matched Study.

BACKGROUND: The aim of this study was to evaluate the long-term nutritional state of patients with gastric cancer who underwent laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DTR) using oblique jejunogastrostomy method (OJG). METHODS: Medical records of 38 patients who underwent LPG-DTR using OJG (21 patients) or laparoscopic total gastrectomy with Roux-en-Y reconstruction (LTG-RY) (17 patients) between October 2011 and March 2018 were retrospectively reviewed. In these patients, clinicopathologic variables were analyzed using propensity score matching for age, sex, body mass index, American Society of Anesthesiologists physical state, clinical stage, and lymph node dissection. Operative outcomes and postoperative nutritional status were compared between the 2 groups. RESULTS: A total of 16 patients were matched to analyze the LPG-DTR and LTG-RY groups. The serum hemoglobin, total protein, and albumin levels at 12 months postoperatively (P=0.008, 0.034, and 0.049) and serum hemoglobin level at 24 months (P=0.025) in the LPG-DTR group was significantly superior to those in the LTG-RY group. CONCLUSIONS: The postoperative nutritional status as long-term outcomes of patients who underwent LPG-DTR using OJG was significantly superior to those who underwent LTG-RY. The results hereby presented suggest that LPG-DTR using OJG for gastric cancer produces better postoperative nutritional status.

Robot-assisted laparoscopic total gastrectomy for Epstein-Barr virus-associated multiple gastric cancer: A case report.

INTRODUCTION: Epstein-Barr virus-associated gastric cancer (EBVaGC) sometimes appears as multiple gastric cancer lesions. Here, we report a case of robot-assisted laparoscopic total gastrectomy (RTG) for a relatively rare disease with four synchronized lesions in EBVaGC and discuss the usefulness of robotic gastrectomy. PRESENTATION OF CASE: A 60-year-old woman was diagnosed with multiple gastric cancer because she had five lesions in the stomach and biopsy showed the presence of adenocarcinoma in four of the five lesions. We performed robot-assisted laparoscopic total gastrectomy on the patient. The histopathological diagnosis was multiple gastric cancer T1bN0M0 pStage IA. The four lesions were positive for the Epstein-Barr virus encoding region in in-situ hybridization and were considered to be EBVaGC. The patient had no sign of recurrence without postoperative therapy for 24 months. DISSCUSSION: EBVaGC was found in about 10% of all gastric cancer cases worldwide. EBVaGC sometimes appears as multiple gastric cancer, suggesting that EBV infection is closely related to the early stages of tumor formation. Total gastrectomy may be necessary for multiple gastric cancer such as EBVaGC, and robotic surgery is useful in total gastrectomy in terms of high-resolution three-dimensional images and using forceps with multi-joint functions. CONCLUSIONS: We performed RTG on a patient with four synchronous lesions of EBVaGC, which is relatively rare. Robot-assisted laparoscopic total gastrectomy is known to be a safe procedure, and we effectively performed total gastrectomy for multiple EBVaGC.

Laparoscopic partial splenectomy for splenic lymphangioma: a case report.

BACKGROUND: Lymphangioma is a benign malformation of the lymphatic system and is often found in the neck and axilla, the orbit, the mediastinum, etc. However, isolated splenic lymphangioma is a rare disease in young women, and its treatment is controversial. We report a case of laparoscopic partial splenectomy for isolated splenic lymphangioma in a young woman. CASE PRESENTATION: An 18-year-old woman with mild epigastralgia was admitted to a nearby hospital. Abdominal ultrasound detected a 6-cm mass confined to the upper pole of the spleen; thereafter, she was referred to our department for surgical treatment. Although a benign tumor, we decided to resect it because of her symptoms. To preserve part of the normal spleen, laparoscopic partial splenectomy was performed with a co-axial approach using four ports and a liver retractor in the lithotomy position. After dissection around the spleen hilum, we identified that the tumor was being fed from the splenic vessels of the upper pole and severed the branch. Postoperatively, the patient showed no complications and was discharged on postoperative day 8 without symptoms. Pathological examination revealed splenic lymphangioma, which is rare in young women. No recurrence was seen 1 year after surgery, and a computed tomography scan showed no problems with the remaining spleen. CONCLUSIONS: In our experience of laparoscopic partial splenectomy for a young woman with an isolated splenic lymphangioma, we determined that laparoscopic partial splenectomy is a safe, effective, and valuable option for the treatment of benign splenic tumors.

Investigation of anti-tumor effect of doxorubicin-loaded human serum albumin nanoparticles prepared by a desolvation technique.

PURPOSE: Nanoparticles of human serum albumin (HSA) prepared using a desolvation method possess sizes suitable for tumor accumulation. Here, we report on an investigation of the anti-tumor effects and biodistribution of doxorubicin-HSA nanoparticles in vitro and in vivo. METHODS: The cytotoxicity of nanoparticles was evaluated in 2D and 3D colon 26 cell cultures. Furthermore, the biodistribution and the anti-tumor activity of nanoparticles in colon 26-bearing mice were investigated. Assessments on the effect on metastasis and the toxicity were also carried out. RESULTS: Doxorubicin-HSA nanoparticles showed cytotoxicity in colon 26 cancer cell cultures, although the cytotoxicity was less in the case of nanoparticles than in free doxorubicin. In vivo anti-tumor activity was more pronounced in nanoparticles despite the fact that their accumulation in tumors was not superior to that of free doxorubicin, suggesting that factors other than accumulation contribute to the enhanced anti-tumor activity of these nanoparticles. The administration of nanoparticles also resulted in the suppression of metastasis. CONCLUSIONS: The prepared nanoparticles appear to be effective for cancer therapy although further studies will be needed to clarify the details of anti-tumor activity and the toxicity of these nanoparticles.

Preparation and in Vitro Analysis of Human Serum Albumin Nanoparticles Loaded with Anthracycline Derivatives.

Nanoparticles prepared using human serum albumin (HSA) have emerged as versatile carriers for improving the pharmacokinetic profile of drugs. The desolvation of HSA using ethanol followed by stabilization through crosslinking with glutaraldehyde is a common technique for preparing HSA nanoparticles, but our knowledge concerning the characteristics (or functions) of HSA nanoparticles and their efficiency when loaded with drugs is limited. To address this issue in more detail, we prepared anthracycline-loaded HSA nanoparticles. Doxorubicin-loaded HSA nanoparticles with a size similar to doxorubicin-unloaded particles could be prepared by desolvating at a higher pH (8-9), and the size (100-150 nm) was optimum for delivery to tumor tissues. Using this procedure, HSA nanoparticles were loaded with other anthracycline derivatives, and all showed cytotoxicity in cancer cells. However, the efficiency of drug loading and dissolution rate were different among them possibly due to the differences in the type of association of the drugs on nanoparticles (doxorubicin and daunorubicin; covalently bound to nanoparticles, pirarubicin; both covalently bound to and adsorbed on nanoparticles, aclarubicin; adsorbed on nanoparticles). Since the formulation of such drug-loaded HSA nanoparticles should be modified for efficient delivery to tumors, the findings reported herein provide the useful information for optimizing the formulation and the production process for the HSA nanoparticles using a desolvation technique.

A novel and conserved protein AHO-3 is required for thermotactic plasticity associated with feeding states in Caenorhabditis elegans.

Although a large proportion of molecules expressed in the nervous system are conserved from invertebrate to vertebrate, functional properties of such molecules are less characterized. Here, we show that highly conserved hydrolase AHO-3 acts as a novel regulator of starvation-induced thermotactic plasticity in Caenorhabditis elegans. As wild-type animals, aho-3 mutants migrated to the cultivation temperature on a linear thermal gradient after cultivation at a particular temperature with food. Whereas wild-type animals cultivated under food-deprived condition showed dispersed distribution on the gradient, aho-3 mutants exhibited tendency to migrate toward higher temperature. Such an abnormal behavior was completely rescued by the expression of human homologue of AHO-3, indicating that the molecular function of AHO-3 is highly conserved between nematode and human. The behavioral regulation by AHO-3 requires the N-terminal cysteine cluster, which ensures the proper subcellular localization of AHO-3 to sensory endings. Double-mutant analysis suggested that AHO-3 acts in the same pathway with ODR-3, a heterotrimeric G protein alpha subunit. Our results unveiled a novel neural protein in C. elegans, confirming its conserved role in behavioral regulation.

Biomechanical study of the effect of degree of static compression of the spinal cord in ossification of the posterior longitudinal ligament.

OBJECT: The authors evaluated the biomechanical effect of 3 different degrees of static compression in a model of the spinal cord in order to investigate the effect of cord compression in patients with ossification of the posterior longitudinal ligament (OPLL). METHODS: A 3D finite element spinal cord model consisting of gray matter, white matter, and pia mater was established. As a simulation of OPLL-induced compression, a rigid plate compressed the anterior surface of the cord. The degrees of compression were 10, 20, and 40% of the anteroposterior (AP) diameter of the cord. The cord was supported from behind by the rigid body along its the posterior border, simulating the lamina. Stress distributions inside of the cord were evaluated. RESULTS: The stresses on the cord were very low under 10% compression. At 20% compression, the stresses on the cord increased very slightly. At 40% compression, the stresses on the cord became much higher than with 20% compression, and high stress distributions were observed in gray matter and the lateral and posterior funiculus. The stresses on the compressed layers were much higher than those on the uncompressed layer. CONCLUSIONS: The stress distributions at 10 and 20% compression of the AP diameter of the spinal cord were very low. The stress distribution at 40% compression was much higher. The authors conclude that a critical point may exist between 20 and 40% compression of the AP diameter of the cord such that when the degree of the compression exceeds this point, the stress distribution becomes much higher, and that this may contribute to myelopathy.