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The three-dimensional folding of chromosomes is essential for nuclear functions such as DNA replication and gene regulation. The emergence of chromatin architecture is thus an important process during embryogenesis. To shed light on the molecular and kinetic underpinnings of chromatin architecture formation, we characterized biophysical properties of cohesin and CTCF binding to chromatin and their changes upon cofactor depletion using single-molecule imaging in live developing zebrafish embryos. We found that chromatin-bound fractions of both cohesin and CTCF increased significantly between the 1000-cell and shield stages, which we could explain through changes in both their association and dissociation rates. Moreover, increasing binding of cohesin restricted chromatin motion, potentially via loop extrusion, and showed distinct stage-dependent nuclear distribution. Polymer simulations with experimentally derived parameters recapitulated the experimentally observed gradual emergence of chromatin architecture. Our findings reveal molecular kinetics underlying chromatin architecture formation during zebrafish embryogenesis. Using single-molecule tracking of cohesin and CTCF during zebrafish embryogenesis, the molecular kinetics underlying chromatin architecture formation was revealed and gradual emergence of chromatin structure recapitulated by polymer simulations.

Background Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Overall surgical experience with minimally invasive surgery (MIS) has increased; however, published reports on MIS resection of GIST are limited to small, single-institution experiences. Methods A total of 397 patients who underwent open surgery ( n = 230) or MIS ( n = 167) for a gastric GIST between 1998 and 2012 were identified from a multicenter database. The impact of MIS approach on recurrence and survival was analyzed using propensity-score matching by comparing clinicopathologic factors between patients who underwent MIS versus open resection. Results There were 19 conversions (10 %) to open; the most common reasons for conversion were tumor more extensive than anticipated (26 %) and unclear anatomy (21 %). On multivariate analysis, smaller tumor size and higher body mass index (BMI) were associated with receipt of MIS. In the propensity-matched cohort ( n = 248), MIS resection was associated with decreased length of stay (MIS, 3 days vs open, 8 days) and fewer ≥ grade 3 complications (MIS, 3 % vs open, 14 %) compared with open surgery. High rates of R0 resection and low rates of tumor rupture were seen in both groups. After propensity-score matching, there was no difference in recurrence-free or overall survival comparing the MIS and the open group (both p > 0.05). Conclusions An MIS approach for gastric GIST was associated with low morbidity and a high rate of R0 resection. The long-term oncological outcome following MIS was excellent, and therefore the MIS approach should be considered the preferred approach for gastric GIST in well-selected patients.

Neuroblastoma (NBL) is the commonest extra-cranial solid tumor in children and the leading cause of cancer related deaths in childhood between the age of 1 to 4 years. NBL may behave in very different ways, from the less aggressive stage 4S NBL or congenital forms that may resolve without treatment in up to 90% of the children, to the high-risk disseminated stage 4 disease in older children with a cure rate of 35 to 40%. Initial staging is crucial for effective management and radiolabeled metaiodobenzylguanidine (MIBG) with iodine-123 is a powerful tool with a sensitivity around 90% and a specificity close to 100% for the diagnosis of NBL. MIBG scintigraphy is used routinely and is mandatory in most investigational clinical trials both for the initial staging of the disease, the evaluation of the response to treatment, as well as for the detection of recurrence during follow-up. With respect to outcome of children presenting disseminated stage 4 NBL, the role of post-therapeutic [(123)I]MIBG scan has been investigated by several groups but so far there is no consensus whereas a complete or very good partial response as assessed by MIBG may be of prognostic value. NBL needs a multimodality approach at diagnosis and during follow-up and MIBG scintigraphy keeps its pivotal role, in particular with respect to bone marrow involvement and/or cortical bone metastases.

Background Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Adjuvant imatinib therapy has resulted in improved disease-free survival (DFS) following resection of primary GIST. The aim of our study was to create a nomogram to predict DFS following resection of GIST. Method Using a multi-institutional cohort of patients who underwent surgery for primary GIST at 7 academic hospitals in the USA and Canada between January 1998 and December 2012, a multivariable Cox proportional hazards model predicting DFS was created using backward stepwise selection. A nomogram to predict DFS following surgical resection of GIST was constructed with the variables selected in the multivariable model. We tested nomogram discrimination by calculating the C-statistic and compared the nomogram to four existing GIST prognostic stratification systems. Results A total of 365 patients who underwent surgery for primary GIST was included in the study. Using backward stepwise selection, sex, tumor size, tumor site, and mitotic rate were selected for incorporation into the nomogram. The nomogram demonstrated superior discrimination compared to the NIH criteria, modified NIH criteria, and Memorial Sloan-Kettering Nomogram and had similar discrimination to the Miettinen criteria (C-statistic 0.77 vs 0.73, 0.71, 0.71, and 0.78, respectively). Conclusion Four independent predictors of recurrence following surgery for primary GIST were used to create a nomogram to predict DFS. The nomogram stratified patients into prognostic groups and performed well on internal validation.

About 1%–2% of pregnant patients develop conditions that require emergency general surgery (EGS). The diagnosis and management of these conditions can be challenging, as surgeons must carefully balance the needs of the pregnant patient and the developing fetus. We sought to summarize the latest literature guiding surgical management of appendicitis, benign biliary disease, bowel obstruction, and hemorrhoids in pregnant patients. We performed a comprehensive scoping review using OVID Medline for articles published between January 2000 and June 2023 pertaining to EGS and pregnancy. Acute appendicitis, benign biliary disease, and bowel obstructions confer increased risk of adverse maternal and fetal obstetrical outcomes. In general, pregnant patients with acute appendicitis and cholecystitis should undergo appendectomy or cholecystectomy, respectively. The management of biliary colic has significant nuance depending on trimester. While an operative approach is favoured in the first 2 trimesters, the role of surgery in the third trimester is less clear. Nonoperative treatment of each of these diseases can result in significant maternal, and possibly fetal, morbidity. Operative management of bowel obstruction must be determined on a case-by-case basis. In all instances, a laparoscopic approach is preferred, if feasible. A thoughtful approach is crucial for surgeons and institutions caring for pregnant patients with EGS diseases. Treatment should be similar to that in nonpregnant patients, with some important considerations and modifications. Nonoperative or delayed operative management often increases adverse obstetrical events, including death. Environ 1 %–2 % des personnes enceintes devront subir une intervention urgente en chirurgie générale pour un problème de santé dont le diagnostic et la prise en charge sont parfois complexes, car il faut judicieusement prendre en compte les besoins de la personne enceinte et ceux du foetus. Nous avons voulu faire le point sur les directives récemment publiées relativement au traitement chirurgical de l’appendicite, de la maladie biliaire bénigne, de l’obstruction intestinale et des hémorroïdes chez les personnes enceintes. Nous avons procédé à une étude de portée globale à partir du réseau OVID Medline pour y trouver les articles publiés entre janvier 2000 et juin 2023 sur les interventions d’urgence en chirurgie générale et la grossesse. L’appendicite, la maladie biliaire bénigne et l’obstruction intestinale aggravent le risque de complications maternelles et foetales. En général, les personnes enceintes aux prises avec une appendicite ou une cholécystite doivent subir respectivement une appendicectomie ou cholécystectomie. La prise en charge de la colique hépatique varie selon trimestre de grossesse. Une approche chirurgicale est préférable au cours des 2 premiers trimestres, mais son rôle est moins clair pour le troisième trimestre. L’approche non chirurgicale pour chacun de ces problèmes de santé peut comporter une morbidité maternelle significative et une morbidité foetale potentielle. Le recours à la chirurgie pour l’obstruction intestinale est déterminé au cas par cas. Une approche laparoscopique est toujours à privilégier si possible. Les établissements qui ont un service d’obstétrique et les équipes chirurgicales doivent impérativement adopter une approche rigoureuse face à des personnes enceintes nécessitant une intervention en chirurgie générale. Le traitement doit équivaloir à celui qui est destiné aux personnes non enceintes, moyennant certaines considérations et modifications importantes. Les modalités non chirurgicales ou un retard à les appliquer augmentent souvent le risque de complications obstétricales, y compris un risque de mortalité.

Ptychites is among the most widely distributed ammonoid genera of the Triassic and is namesake of a family and superfamily. However, representatives of the genus mostly show low-level phenotypic disparity. Furthermore, a large number of taxa are based on only a few poorly preserved specimens, creating challenges to determine ptychitid taxonomy. Consequently, a novel approach is needed to improve ptychitid diversity studies. Here, we investigate Ptychites spp. from the middle and late Anisian of Nevada. The species recorded include Ptychites embreei n. sp., which is distinguished by an average conch diameter that is much smaller and shows a more evolute coiling than most of its relatives. The new species ranges from the Gymnotoceras mimetus to the Gymnotoceras rotelliformis zones, which makes it the longest-ranging species of the genus. For the first time, the ontogenetic development of Ptychites was obtained from cross sections where possible. Cross-sectioning highlights unique ontogenetic trajectories in ptychitids. This demonstrates that, despite showing little phenotypic disparity, Ptychites was highly ontogenetically differentiated, and thus the high taxonomic diversity at the species level is justified for the species investigated.

BackgroundCytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) can be associated with decreases in quality of life (QOL). Bowel-related QOL (BR-QOL) after CRS-HIPEC has not been previously studied. The objectives of the current study were to examine the effect of different types of bowel resection during CRS-HIPEC on overall QOL and BR-QOL.MethodsA prospective cohort study was performed. QOL data were collected using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR-29 questionnaires at 3, 6, and 12 months after CRS-HIPEC. Patients were divided into groups that underwent no bowel resection, non-low anterior resection (LAR) bowel resection, LAR, and LAR with stoma. Primary outcomes were global QOL and BR-QOL.ResultsOverall, 158 patients were included in this study. Bowel resections were performed in 77% of patients, with 31% undergoing LAR. Global QOL was not significantly different between groups. LAR patients (with and without stoma) had significantly worse BR-QOL, embarrassment, and altered body image, with LAR + stoma patients having the largest impairments in these domains. Trends toward higher levels of impotence and anxiety were also seen in LAR patients. Although global QOL improved over time, impairments in BR-QOL and sexual and social function did not significantly improve over time.ConclusionsAlthough global QOL after CRS-HIPEC was not affected by the type of bowel resection, the use of LAR and ostomies was associated with clinically meaningful and persistent impairments in BR-QOL and related functional domains. Generic QOL questionnaires may not adequately capture these domains; however, targeted questionnaires in these patients may help improve QOL after CRS-HIPEC.

Background: In recent years experience has been accumulated in percutaneous radiofrequency ablation (RFA) of lung malignancies in nonsurgical patients. Objectives: In this study, we retrospectively evaluated a simultaneous diagnostic and therapeutic approach including CT-guided biopsy followed immediately by RFA of solitary malignant pulmonary lesions. Methods: CT-guided transthoracic core needle biopsy of solitary pulmonary lesions suspicious for malignancy was performed and histology was proven based on immediate frozen sections. RFA probes were placed into the pulmonary tumors under CT guidance and the ablation was performed subsequently. The procedure-related morbidity was analyzed. Follow-up included a CT scan and pulmonary function parameters. Results: A total of 33 CT-guided biopsies and subsequent RFA within a single procedure were performed. Morbidity of CT-guided biopsy included pulmonary hemorrhage (24%) and a mild pneumothorax (12%) without need for further interventions. The RFA procedure was not aggravated by the previous biopsy. The rate of pneumothorax requiring chest tube following RFA was 21%. Local tumor control was achieved in 77% with a median follow-up of 12 months. The morbidity of the CT-guided biopsy had no statistical impact on the local recurrence rate. Conclusions: The simultaneous diagnostic and therapeutic approach including CT-guided biopsy followed immediately by RFA of solitary malignant pulmonary lesions is a safe procedure. The potential of this combined approach is to avoid unnecessary therapies and to perform adequate therapies based on histology. Taking the local control rate into account, this approach should only be performed in those patients who are unable to undergo or who refuse surgery.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third leading cause of cancer death worldwide. Recurrence rates after curative intent treatment for HCC are high; 5-year disease-free survival ranges from only 19 to 81 %. There is no direct evidence to guide the optimal frequency and method of surveillance for recurrent HCC after curative intent treatment. In contrast, there is strong evidence supporting both primary screening for HCC in patients with chronic liver disease. After resection, HCC tends to recur locally, whereas the pattern after transplantation is more at extrahepatic sites. In theory, if an HCC recurrence is discovered early, more therapeutic options are available for treatment of the recurrent HCC. As such, close surveillance after curative intent therapy may have the potential to prolong survival. We herein review the available literature derived from primary surveillance of patients with cirrhosis, as well as data on postoperative surveillance of HCC patients. In aggregate, although data remain scarce, close surveillance with α-fetoprotein and cross-sectional imaging every 3–4 months for 3 years after curative intent therapy, followed by surveillance every 6–12 months thereafter, seems the most prudent approach to follow-up of patients with HCC in the postsurgical setting.

Background: Prevalence studies of Internet addiction in the general population are rare. In addition, a lack of approved criteria hampers estimation of its occurrence. Aims: This study conducted a latent class analysis (LCA) in a large general population sample to estimate prevalence. Methods: A telephone survey was conducted based on a random digit dialling procedure including landline telephone (n = 14,022) and cell phone numbers (n = 1,001) in participants aged 14-64. The Compulsive Internet Use Scale (CIUS) served as the basis for a LCA used to look for subgroups representing participants with Internet addiction or at-risk use. CIUS was given to participants reporting to use the Internet for private purposes at least 1 h on a typical weekday or at least 1 h on a day at the weekend (n = 8,130). Results: A 6-class model showed best model fit and included two groups likely to represent Internet addiction and at-risk Internet use. Both groups showed less social participation and the Internet addiction group less general trust in other people. Proportions of probable Internet addiction were 1.0% (CI 0.9-1.2) among the entire sample, 2.4% (CI 1.9-3.1) in the age group 14-24, and 4.0% (CI 2.7-5.7) in the age group 14-16. No difference in estimated proportions between males and females was found. Unemployment (OR 3.13; CI 1.74-5.65) and migration background (OR 3.04; CI 2.12-4.36) were related to Internet addiction. Conclusions: This LCA-based study differentiated groups likely to have Internet addiction and at-risk use in the general population and provides characteristics to further define this rather new disorder.