bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of learning curve of robot‐assisted laparoscopy on oncological outcomes in early‐stage cervical cancer: an observational cohort study
Authors: Baeten IGT , Hoogendam JP , Schreuder HWR , Jürgenliemk‐Schulz IM , Verheijen RHM , Zweemer RP , Gerestein CG 
Published: July 2020

ObjectiveTo investigate the learning curve of robot‐assisted laparoscopy in early‐stage cervical cancer and quantify impact on oncological outcomes.DesignObservational cohort study.SettingTertiary referral centre with one surgical team.PopulationAll women with early‐stage cervical cancer treated consecutively with robot‐assisted laparoscopy between 2007 and 2017.MethodsWith multivariate risk‐adjusted cumulative sum analysis (RA‐CUSUM), we assessed the learning curve of robot‐assisted laparoscopy of a single surgical team based on cervical cancer recurrence. Subsequently, a survival analysis was conducted comparing oncological outcomes of women treated during different phases of the learning curve.Main outcome measuresSurgical proficiency based on recurrence, survival rates in the different learning phases.ResultsOne hundred and sixty‐five women with cervical cancer underwent robot‐assisted laparoscopy, with a median follow up of 57 months (range 3–132 months). The RA‐CUSUM analysis demonstrated two phases of the learning curve: a learning phase of 61 procedures (group 1) and an experienced phase representing the 104 procedures thereafter (group 2). The 5‐year disease‐free survival was 80.2% in group 1 and 91.1% in group 2 (P = 0.040). Both the 5‐year disease‐specific survival and overall survival significantly increased after the learning phase.ConclusionThe learning phase of robot‐assisted laparoscopy in early‐stage cervical cancer in this institutional cohort is at least 61 procedures, with higher survival rates in the women treated thereafter. The learning curve of robot‐assisted laparoscopy affects oncological outcomes and warrants more attention in the design of future studies.Tweetable abstractThe learning curve of robot‐assisted laparoscopy in early‐stage cervical cancer affects oncological outcomes and warrants more attention.
High‐quality Digital 3D Reconstruction of Microscopic Findings in Forensic Pathology: The Terminal Pathway of a Heart Stab Wound*
Authors: Porzionato Andrea , Guidolin Diego , Emmi Aron , Boscolo‐Berto Rafael , Sarasin Gloria , Rambaldo Anna , Macchi Veronica , De Caro Raffaele 
Published: July 2020

AbstractHigh‐quality digital three‐dimensional (3D) reconstructions of microscopic findings have been used in anatomical and histopathologic research, but their use in forensic pathology may also be of interest. This paper presents an application of these methods to better characterize the pathway of a stab wound of the anterior surface of the heart in a case of suicide. A portion of the heart wall including the stab wound was serially sectioned for microscopic analysis along the full extent of the wound. Histologic sections were digitally acquired, and a 3D reconstruction was created with ImageJ software for 3D computer graphics. This showed a full‐thickness wound path extending to the endocardial surface of the left ventricle, curvilinear in appearance. After correction for shrinkage, 3D reconstruction allowed estimation of the dimensions of the myocardial injury and comparison of the appearance of the wound with the suspected knife used. The curvilinear appearance was considered to reflect injury during myocardial contraction. Complete microscopic sectioning and 3D reconstruction may allow virtual sectioning through various orientations and also provide useful forensic information for selected injuries.
Rating shopping: evidence from the Chinese corporate debt security market
Authors: Chang Zhang , Hu Xiaolu , Pan Zheyao , Shi Jing 
Published: July 2020

AbstractWe provide the first direct evidence on how issuers choose a credit rating agency (CRA). Using rating data from a leading CRA in China, we find that although in most cases the issuers publish more favourable ratings, in some cases issuers just select the ratings provided by CRAs they have business relationships with, especially when the more favourable ratings are above issuers’ prior ratings. Our further analysis suggests that this phenomenon is driven by the switching cost arising from the issuer being considered as a rating shopper when it obtains an upgrade from a CRA without a business relationship.
Land cover change of arid environment in Tunisia based on analysis of Landsat images
Authors: Henchiri Malak , Zhang Sha , Essifi Bouajila , Ouessar Mohamed , Bai Yun , Jiahua Zhang 
Published: July 2020

AbstractThe impact of Land use/land cover (LULC) change was assessed through monitoring the distribution of ecological indicators and tracking the aeolian deposits, which provides valuable information on desertification and climate change in Tunisian arid regions. This study was conducted in Oum Zessar area, in southeastern Tunisia. Both visual interpretation and automated classification approach were developed to extract sand features using Landsat images for 2000, 2008 and 2014. The automated classification includes a decision tree classifier (DT) and an unsupervised classification applied to the principal components extracted from Knepper ratios composite. The validation of the classification methods showed that the DT had an overall accuracy over 84%. The results of the change detection have shown an increase in the classes of Agriculture behind tabia by 10.68%, the rangelands and croplands by 24.37% and the mountain rangelands by 14.93%, and a decrease in the classes of Agriculture behind jessour by 33.65%, sand encroachments by 12.93% and halophyte rangelands by 3.4%, respectively. These resulting maps seem to be the suitable decision‐support tools for management of land use in arid regions of Tunisia, in particular, for land degradation assessment and water and soil conservation.
Proliferation does not contribute to murine models of renin cell recruitment
Authors: Guessoum Omar , Zainab Momna , Sequeira‐Lopez Maria Luisa S. , Gomez R. Ariel 
Published: July 2020

AbstractAimRenin cells are essential for regulation of blood pressure and fluid‐electrolyte homeostasis. During homeostatic threat, the number of renin cells in the kidney increases, a process termed as recruitment. It has been proposed that recruitment occurs by proliferation, yet no systematic studies have been performed. We sought to determine the extent to which proliferation contributes to the recruitment process.MethodsMice were subjected to recruitment before analysing the renin cells’ cell cycle. For acute threats, we subjected SV129 and C57Bl6 mice to a low sodium diet plus captopril. Tissue sections from treated mice were co‐stained for proliferation markers (Ki67, PCNA, pH3 and BrdU) and renin. Chronic recruitment was studied in deletion models of aldosterone synthase and angiotensinogen through co‐immunostaining and counting mitotic figures in periodic acid‐Schiff‐stained sections. Finally, RNA‐seq of renin cells isolated from recruited mice was performed to study mitotic signature.ResultsMice subjected to low salt and captopril displayed increases in renin cell number (312 ± 40 in controls to 692 ± 85 in recruited animals, P<.0001), 10‐fold increases in renin mRNA and fourfold increases in circulating renin. Co‐staining these kidney sections for proliferation markers revealed negligible proliferation of renin cells (<2%), indistinguishable from control animals. Similarly, chronic models of recruitment—aldosterone synthase KO and angiotensinogen KO—had negligible proliferation. Additionally, the transcriptome of recruited renin cells revealed overall downregulation of mitotic pathways when compared to proliferative cell lines.ConclusionAcute and chronic physiological threats to homeostasis produced a distinct increase in renin‐synthesizing cells, but we found no evidence to suggest the involvement of proliferation.
A Bayesian hierarchical model for characterizing the diffusion of new antipsychotic drugs
Authors: Gu Chenyang , Huskamp Haiden , Donohue Julie , Normand Sharon‐Lise 
Published: July 2020

AbstractNew prescription medications are a primary driver of spending growth in the United States. For patients with severe mental illnesses, second‐generation antipsychotic (SGA) medications feature prominently. However, many SGAs are costly, particularly before generic entry, and some may increase the risk of diabetes. Because physicians play a prominent role in new prescription adoption, understanding their prescribing behaviors is policy‐relevant. Several features of prescription data, such as different antipsychotic choice sets over time, variable physician prescription volumes, and correlation among drug choices within physicians, complicate inferences. We propose a multivariate Bayesian hierarchical model with piecewise random effects to characterize the diffusion of new antipsychotic drugs. This model captures the complex prescriber‐specific relationships among the different diffusion processes and takes advantage of the Bayesian paradigm to quantify uncertainty for all parameters straightforwardly. To evaluate the prescribing patterns for each physician, we propose various indices to identify early new SGA adopters. A sample of nearly 17,000 US physicians whose antipsychotic drug prescribing information was collected between January 1, 1997 and December 31, 2007 illustrates the methods. Determinants of high prescription rates and adoption speeds of new SGAs included physician sex, age, hospital affiliation, physician specialty, and office location. Large within‐ and between‐provider variations in prescribing patterns of new SGAs were identified. Early adopters for one drug were not early adopters for another drug.
Clinical utility of target capture‐based panel sequencing in hematological malignancies: A multicenter feasibility study
Authors: Yasuda Takahiko , Sanada Masashi , Nishijima Dai , Kanamori Takashi , Iijima Yuka , Hattori Hiroyoshi , Saito Akiko , Miyoshi Hiroaki , Ishikawa Yuichi , Asou Norio , Usuki Kensuke , Hirabayashi Shinsuke , Kato Motohiro , Ri Masaki , Handa Hiroshi , Ishida Tadao , Shibayama Hirohiko , Abe Masahiro , Iriyama Chisako , Karube Kennosuke , Nishikori Momoko , Ohshima Koichi , Kataoka Keisuke , Yoshida Kenichi , Shiraishi Yuichi , Goto Hiroaki , Adachi Souichi , Kobayashi Ryoji , Kiyoi Hitoshi , Miyazaki Yasushi , Ogawa Seishi , Kurahashi Hiroki , Yokoyama Hisayuki , Manabe Atsushi , Iida Shinsuke , Tomita Akihiro , Horibe Keizo 
Published: July 2020

AbstractAlthough next‐generation sequencing‐based panel testing is well practiced in the field of cancer medicine for the identification of target molecules in solid tumors, the clinical utility and clinical issues surrounding panel testing in hematological malignancies have yet to be fully evaluated. We conducted a multicenter prospective clinical sequencing study to verify the feasibility of a panel test for hematological tumors, including acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma, and diffuse large B‐cell lymphoma. Out of 96 eligible patients, 79 patients (82%) showed potentially actionable findings, based on the clinical sequencing assays. We identified that genetic alterations with a strong clinical significance were found at a higher frequency in terms of diagnosis (n = 60; 63%) and prognosis (n = 61; 64%) than in terms of therapy (n = 8; 8%). Three patients who harbored a germline mutation in either DDX41 (n = 2) or BRCA2 (n = 1) were provided with genetic counseling. At 6 mo after sequencing, clinical actions based on the diagnostic (n = 5) or prognostic (n = 3) findings were reported, but no patients were enrolled in a clinical trial or received targeted therapies based on the sequencing results. These results suggest that panel testing for hematological malignancies would be feasible given the availability of useful diagnostic and prognostic information. This study is registered with the UMIN Clinical Trial Registry (UMIN000029879, multiple myeloma; UMIN000031343, adult acute myeloid leukemia; UMIN000033144, diffuse large B‐cell lymphoma; and UMIN000034243, childhood leukemia).
Ribociclib, a CDK 4/6 inhibitor, plus endocrine therapy in Asian women with advanced breast cancer
Authors: Yap Yoon‐Sim , Chiu Joanne , Ito Yoshinori , Ishikawa Takashi , Aruga Tomoyuki , Kim Seung Jin , Toyama Tatsuya , Saeki Toshiaki , Saito Mitsue , Gounaris Ioannis , Su Fei , Ji Yan , Han Yu , Gazdoiu Mihaela , Masuda Norikazu 
Published: July 2020

AbstractThe ongoing, Phase Ib MONALEESASIA study is evaluating the efficacy and safety of ribociclib plus endocrine therapy in Asian patients with hormone receptor‐positive, human epidermal growth factor receptor 2‐negative advanced breast cancer. Eligible patients from Japan, Hong Kong, and Singapore were enrolled in this 2‐phase study consisting of a dose‐escalation phase to determine the maximum‐tolerated dose and the recommended Phase II dose of ribociclib plus letrozole, and a dose‐expansion phase to evaluate safety and tolerability of ribociclib plus letrozole, fulvestrant, or tamoxifen. An exploratory biomarker analysis evaluating expression of target genes was also conducted. In the dose‐escalation phase, the maximum‐tolerated/recommended Phase II doses of ribociclib were lower in Japanese patients (300 mg) than in Asian non‐Japanese patients (600 mg). Ribociclib plus endocrine therapy at the recommended Phase II dose had a manageable safety profile, with neutropenia and elevated liver transaminases being the most common adverse events leading to dose modifications or discontinuations, and it demonstrated evidence of clinical activity in both Japanese and Asian non‐Japanese patients. Preliminary efficacy in Asian populations is similar to that observed in White populations studied in previous ribociclib (MONALEESA) trials. Biomarker analysis demonstrated suppression of pharmacodynamic biomarker gene expression, indicating inhibition of target genes by ribociclib combined with endocrine therapy. Results from the ongoing study support the use of ribociclib in combination with letrozole in Asian non‐Japanese patients at the same dose (600 mg) as White patients. In Japanese patients, a lower dose of ribociclib (300 mg) should be considered. Clinicaltrials.gov: NCT02333370.
De novo missense variants in the RAP1B gene identified in two patients with syndromic thrombocytopenia
Authors: Niemann Jan Hendrik , Du Chen , Morlot Susanne , Schmidt Gunnar , Auber Bernd , Kaune Beate , Göhring Gudrun , Ripperger Tim , Schlegelberger Brigitte , Hofmann Winfried , Smol Thomas , Ait‐Yahya Emilie , Raimbault Anna , Lambilliotte Anne , Petit Florence , Steinemann Doris 
Published: July 2020

AbstractWe present two independent cases of syndromic thrombocytopenia with multiple malformations, microcephaly, learning difficulties, dysmorphism and other features. Exome sequencing identified two novel de novo heterozygous variants in these patients, c.35G>T p.(Gly12Val) and c.178G>C p.(Gly60Arg), in the RAP1B gene (NM_001010942.2). These variants have not been described previously as germline variants, however functional studies in literature strongly suggest a clinical implication of these two activating hot spot positions. We hypothesize that pathogenic missense variants in the RAP1B gene cause congenital syndromic thrombocytopenia with a spectrum of associated malformations and dysmorphism, possibly through a gain of function mechanism.
Predicting outcomes of pelvic exenteration using machine learning
Authors:   PelvEx Collaborative
Published: July 2020

AbstractAimWe aim to compare machine learning with neural network performance in predicting R0 resection (R0), length of stay > 14 days (LOS), major complication rates at 30 days postoperatively (COMP) and survival greater than 1 year (SURV) for patients having pelvic exenteration for locally advanced and recurrent rectal cancer.MethodA deep learning computer was built and the programming environment was established. The PelvEx Collaborative database was used which contains anonymized data on patients who underwent pelvic exenteration for locally advanced or locally recurrent colorectal cancer between 2004 and 2014. Logistic regression, a support vector machine and an artificial neural network (ANN) were trained. Twenty per cent of the data were used as a test set for calculating prediction accuracy for R0, LOS, COMP and SURV. Model performance was measured by plotting receiver operating characteristic (ROC) curves and calculating the area under the ROC curve (AUROC).ResultsMachine learning models and ANNs were trained on 1147 cases. The AUROC for all outcome predictions ranged from 0.608 to 0.793 indicating modest to moderate predictive ability. The models performed best at predicting LOS > 14 days with an AUROC of 0.793 using preoperative and operative data. Visualized logistic regression model weights indicate a varying impact of variables on the outcome in question.ConclusionThis paper highlights the potential for predictive modelling of large international databases. Current data allow moderate predictive ability of both complex ANNs and more classic methods.
Native distribution characteristics rather than functional traits explain preadaptation of invasive species to high‐UV‐B environments
Authors: Hock Maria , Hofmann Rainer , Essl Franz , Pyšek Petr , Bruelheide Helge , Erfmeier Alexandra 
Published: July 2020

AbstractAimAlien species successfully colonize new ranges if they encounter favourable environmental conditions there and possess traits that match new challenges. Climate‐matching approaches comparing native and exotic ranges mostly consider temperature and precipitation niches of alien species, but have largely ignored UV‐B radiation. UV‐B fundamentally differs between hemispheres, with much higher levels at southern than at northern latitudes. Consequently, UV‐B might act at the global scale and present a so far neglected filter that species need to overcome when invading high‐UV‐B environments.LocationWe performed two multi‐species common garden experiments, conducted in the native European range (Germany) and the high‐UV‐B exotic range (New Zealand) to test for preadaptation to UV‐B.MethodsWe used 25 herbaceous species from open habitats, which we exposed in each range to three UV radiation treatments: (a) natural sunlight, (b) exclusion of UV‐B while allowing natural UV‐A, and (c) exclusion of UV‐B and UV‐A. We additionally used plant traits (TRY), global distribution data (GBIF, GloNAF) and global UV‐B satellite data (glUV) to determine species‐specific characteristics as fostering agents of UV‐B tolerance. The joint analysis of experimental and macroecological data allowed quantification of species plasticity and identification of beneficial species traits in high‐UV‐B environments.ResultsOur results showed an overall limiting effect of UV‐B in both common gardens but the UV‐stress response tended to be more pronounced in the invaded range. Across all species, we found little evidence for preadaptation by functional plant traits. In contrast, preadaptation to climatic conditions related to the species’ native UV‐B niche was of greater importance for plant performance in the presence of UV‐B radiation.Main conclusionsFor predicting alien species’ ability to expand into high‐UV‐B environments, macroclimatic niche characteristics of the species’ native range might be better predictors than functional traits and should be more considered in future projection models.
Zebrafish models of impulsivity and impulse control disorders
Authors: de Abreu Murilo S. , C. V. V. Giacomini Ana , Genario Rafael , Fontana Barbara D. , Parker Matthew O. , Marcon Leticia , Scolari Naiara , Bueno Barbara , Demin Konstantin A. , Galstyan David , Kolesnikova Tatyana O. , Amstislavskaya Tamara G. , Zabegalov Konstantin N. , Strekalova Tatyana , Kalueff Allan V. 
Published: July 2020

AbstractImpulse control disorders (ICDs) are characterized by generalized difficulty controlling emotions and behaviors. ICDs are a broad group of the central nervous system (CNS) disorders including conduct disorder, intermittent explosive, oppositional‐defiant disorder, antisocial personality disorder, kleptomania, pyromania and other illnesses. Although they all share a common feature (aberrant impulsivity), their pathobiology is complex and poorly understood. There are also currently no ICD‐specific therapies to treat these illnesses. Animal models are a valuable tool for studying ICD pathobiology and potential therapies. The zebrafish (Danio rerio) has become a useful model organism to study CNS disorders due to high genetic and physiological homology to mammals, and sensitivity to various pharmacological and genetic manipulations. Here, we summarize experimental models of impulsivity and ICD in zebrafish and highlight their growing translational significance. We also emphasize the need for further development of zebrafish ICD models to improve our understanding of their pathogenesis and to search for novel therapeutic treatments.
Assessing multifunctionality of agricultural soils: Reducing the biodiversity trade‐off
Authors: Vazquez Carmen , de Goede Ron G. M. , Rutgers Michiel , de Koeijer Tanja J. , Creamer Rachel E. 
Published: July 2020

AbstractSoils are indispensable for the provision of several functions. Agricultural intensification and its focus on increasing primary productivity (PP) poses a threat to soil quality, due to increases in nutrient loads, greenhouse gas emissions and declining biodiversity. The EU Horizon 2020 Landmark project has developed multi‐criteria decision models to assess five soil functions: PP, nutrient cycling (NC), soil biodiversity and habitat provision (B‐HP), climate mitigation and water regulation, simultaneously in agricultural fields. Using these algorithms, we evaluated the supply of PP, NC and B‐HP of 31 grasslands and 21 croplands as low, medium or high. The multi‐criteria decision models showed that 38% of the farms had a medium to high supply of all three soil functions, whereas only one cropland had a high supply for all three. Forty‐eight per cent of the farms were characterized by a high supply of PP and NC. We observed a clear trade‐off between these two functions and B‐HP. Multivariate statistical analyses indicated that higher organic inputs combined with a lower mineral fertilization concur with higher biodiversity scores while maintaining a medium delivery of PP and NC. Additionally, we compared the outputs of the model predictions to independent variables that served as proxies for the soil functions and found: (a) croplands (but not grasslands) with high PP had a higher standardized yield than those with medium PP; (b) grasslands (but not croplands) with high NC had a significantly lower fungal to bacterial biomass ratio, suggesting faster decomposition channels; and (c) a positive though non‐significant trend between B‐HP score and rank according to soil invertebrate biodiversity. These comparisons suggest a successful upscaling of the models from field to farm level. Our study highlights the need for systematic collection of management‐related data for the assessment of soil functions. Multifunctionality can be achieved in agricultural soils; however, without specifically managing for it, biodiversity might come at a loss.Highlights
We study how well soils can provide primary productivity, nutrient cycling and biodiversity.
We study trade‐offs and synergies among soil functions, as well as the drivers of these relationships.
Soil biodiversity is largely sacrificed for primary productivity and nutrient cycling
Changes in pesticide and fertilizer management can increase soil multifunctionality.