bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of a preliminary therapeutic reference range for children and adolescents with tic disorders treated with tiapride
Authors: Fekete Stefanie , Egberts K. , Preissler T. , Wewetzer C. , Mehler-Wex C. , Romanos M. , Gerlach M. 
Published: September 2020

Abstract
Purpose
Tiapride is commonly used in Europe for the treatment of tics. The aim of this study was to examine the relationship between dose and serum concentrations of tiapride and potential influential pharmacokinetic factors in children and adolescents. In addition, a preliminary therapeutic reference range for children and adolescents with tics treated with tiapride was calculated.

Methods
Children and adolescents treated with tiapride at three university hospitals and two departments of child and adolescents psychiatry in Germany and Austria were included in the study. Patient characteristics, doses, serum concentrations, and therapeutic outcome were assessed during clinical routine care using standardised measures.

Results
In the 49 paediatric patients (83.7% male, mean age = 12.5 years), a positive correlation was found between tiapride dose (median 6.9 mg/kg, range 0.97–19.35) and serum concentration with marked inter-individual variability. The variation in dose explained 57% of the inter-patient variability in tiapride serum concentrations; age, gender, and concomitant medication did not contribute to the variability. The symptoms improved in 83.3% of the patients. 27.1% of the patients had mild or moderate ADRs. No patient suffered from severe ADRs.

Conclusions
This study shows that tiapride treatment was effective and safe in most patients with tics. Compared with the therapeutic concentration range established for adults with Chorea Huntington, our data hinted at a lower lower limit (560 ng/ml) and similar upper limit (2000 ng/ml).
Phase I, first-in-human trial of programmed cell death receptor-1 (PD-1) inhibitor, JTX-4014, in adult patients with advanced, refractory, solid tumors
Authors: Papadopoulos Kyriakos P. , Lakhani Nehal , Falchook Gerald S. , Riley Gosia , Baeck Johan , Brown Karen S. , Gordon Gilad , Le Lidya , Wang Judy S. 
Published: September 2020

Abstract
Background
Inhibition of programmed cell death receptor protein-1 (PD-1) has proven to be a highly effective strategy for immunotherapy of cancer. Approvals of both PD-1 and PD-L1 inhibitors [PD-(L)1i] in multiple tumor types are evidence of the durable benefits they provide to patients with cancer. In this first-in-human trial, we assessed the safety and tolerability of JTX-4014, a fully human antibody targeting PD-1.

Methods
JTX-4014 was administered to 18 patients with multiple solid tumor types who had not previously received a PD-(L)1i. The primary objectives were to evaluate the safety and tolerability of JTX-4014 and determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Secondary objectives included evaluation of the pharmacokinetics (PK) of JTX-4014, anti-drug antibodies (ADA) against JTX-4014, and clinical activity.

Results
JTX-4014 was well tolerated and no new safety signals were identified as compared with other PD-1is. The MTD was not reached and the RP2D was selected, based on PK modelling and supportive safety data, to be 500 mg every 3 weeks or 1000 mg every 6 weeks. Clinical activity, based on RECIST v1.1 criteria, demonstrated an overall response rate of 16.7% (n = 3) with one complete and two partial responses and a disease control rate of 44.4% (n = 8). The responses occurred at different doses in patients with PD-L1 positive tumors and in tumor types that are not typically PD-1i responsive.

Conclusions
Further development of JTX-4014 is warranted as a monotherapy or in combination with other innovative cancer therapies.

Trial registration number
NCT03790488, December 31 2018.
Impact of Remnant Carcinoma in Situ at the Ductal Stump on Long‐Term Outcomes in Patients with Distal Cholangiocarcinoma
Authors: Yasukawa Koya , Shimizu Akira , Motoyama Hiroaki , Kubota Koji , Notake Tsuyoshi , Fukushima Kentaro , Ikehara Tomohiko , Hayashi Hikaru , Kobayashi Akira , Soejima Yuji 
Published: September 2020

AbstractBackgroundThe management of positive ductal margins with carcinoma in situ (R1‐CIS) after resection is controversial. The aim of this study was to evaluate the impact of R1‐CIS on survival in patients who underwent resection for distal cholangiocarcinoma.MethodsWe enrolled 121 consecutive patients with distal cholangiocarcinoma. Poor prognostic factors were investigated by multivariable analysis, and we performed a stratified analysis to evaluate the impact of R1‐CIS on survival in patients with or without prognostic factors.ResultsMultivariable analysis identified node‐positive status as the prognostic factor (P = 0.003). Stratified by lymph node status, overall survival (OS) in the R0 group was significantly better than that in the R1‐CIS group in node‐negative patients (57.1% vs 30.0%; P < 0.050). Although OS was comparable between the two groups in node‐positive patients (5‐year OS: 22.2% vs 20.0%, respectively; P = not significant). Furthermore, OS in patients in whom R0 was achieved by additional resection was significantly better than that in patients with R1‐CIS (5‐year OS: 66.7% vs 30.0%, respectively; P < 0.050).ConclusionsRemnant CIS is associated with a poor prognosis in patients with node‐negative distal cholangiocarcinoma. Every effort should be made to achieve negative bile duct margins.
Pairwise relatedness testing in the context of inbreeding: expectation and variance of the likelihood ratio
Authors: Brustad Hilde Kjelgaard , Vigeland Magnus Dehli , Egeland Thore 
Published: September 2020

AbstractIn this paper we investigate various effects of inbreeding on the likelihood ratio (LR) in forensic kinship testing. The basic setup of such testing involves formulating two competing hypotheses, in the form of pedigrees, describing the relationship between the individuals. The likelihood of each hypothesis is computed given the available genetic data, and a conclusion is reached if the ratio of these exceeds some pre-determined threshold. An important aspect of this approach is that the hypotheses are usually not exhaustive: The true relationship may differ from both of the stated pedigrees. It is well known that this may introduce bias in the test results. Previous work has established formulas for the expected value and variance of the LR, given the two competing hypotheses and the true relationship. However, the proposed method only handles cases without inbreeding. In this paper we extend these results to all possible pairwise relationships. The key ingredient is formulating the hypotheses in terms of Jacquard coefficients instead of the more restricted Cotterman coefficients. While the latter describe the relatedness between outbred individuals, the more general Jacquard coefficients allow any level of inbreeding. Our approach also enables scrutiny of another frequently overlooked source of LR bias, namely background inbreeding. This ubiquitous phenomenon is usually ignored in forensic kinship computations, due to lack of adequate methods and software. By leveraging recent work on pedigrees with inbred founders, we show how background inbreeding can be modeled as a continuous variable, providing easy-to-interpret results in specific cases. For example, we show that if true siblings are subjected to a test for parent-offspring, moderate levels of background inbreeding are expected to inflate the LR by more than 50%.
Neonatal spectral EEG is prognostic of cognitive abilities at school age in premature infants without overt brain damage
Authors: Cainelli Elisa , Vedovelli Luca , Wigley Isabella Lucia Chiara Mariani , Bisiacchi Patrizia Silvia , Suppiej Agnese 
Published: September 2020

AbstractPrematurity is a prototype of biological risk that could affect the late neurocognitive outcome; however, the condition itself remains a non-specific marker. This longitudinal 6-year study aimed to evaluate the prognostic role of neonatal spectral EEG in premature infants without neurological complications. The study cohort was 26 children born 23–34 gestational ages; all neonates underwent multichannel EEG recordings at 35 weeks post-conception. EEG data were transformed into the frequency domain and divided into delta (0.5–4 Hz), theta (5–7 Hz), alpha (8–13 Hz), and beta (14–20 Hz) frequency bands. At 6 years, a neuropsychological and behavioral evaluation was performed. Correlations between spectral bands and neuropsychological assessments were performed with a conservative and robust Bayesian correlation model using weakly informative priors. The correlation of neuropsychological tasks to spectral frequency bands highlighted a significant association with visual and auditory attention tests. The performance on the same tests appears to be mainly impaired.Conclusions: We found that spectral EEG frequencies are independent predictors of performance in attention tasks. We hypothesized that spectral EEG might reflect early circuitries’ imbalance in the reticular ascending system and cumulative effect on ongoing development, pointing to the importance of early prognostic instruments.

What is Known:• Prematurity is a non-specific marker of late neurocognitive risk.• Precise prognostic instruments are lacking, mostly in patients with low-grade conditions.What is New:• Longitudinal long-term studies are scarce but crucial for the inferential attributive process.• Spectral EEG frequencies are independent predictors of performance in attention tasks.
Preoperative endoscopic marking of the gastrointestinal tract using fluorescence imaging: submucosal indocyanine green tattooing versus a novel fluorescent over-the-scope clip in a survival experimental study
Authors: Barberio Manuel , Pizzicannella Margherita , Spota Andrea , Ashoka Anila Hoskere , Agnus Vincent , Al Taher Mahdi , Jansen-Winkeln Boris , Gockel Ines , Marescaux Jacques , Swanström Lee , Kong Seong-Ho , Felli Eric , Klymchenko Andrey , Diana Michele 
Published: September 2020

Abstract
Background
Intraoperative localization of endoluminal lesions is can be difficult during laparoscopy. Preoperative endoscopic marking is therefore necessary. Current methods include submucosal tattooing using visible dyes, which in case of transmural injection can impair surgical dissection. Tattooing using indocyanine green (ICG) coupled to intraoperative near-infrared (NIR) laparoscopy has been described. ICG is only visible under NIR-light, therefore, it doesn’t impair the surgical workflow under white light even if there is spillage. However, ICG tattoos have rapid diffusion and short longevity. We propose fluorescent over-the-scope clips (FOSC), using a novel biocompatible fluorescent paint, as durable lesion marking.

Methods
In six pigs, gastric and colonic endoscopic tattoos using 0.05 mg/mL of ICG and markings using the fluorescent OSC were performed (T0). Simultaneously, NIR laparoscopy was executed. Follow-up laparoscopies were conducted at postoperative day (POD) 4–6 (T1) and POD 11–12 (T2). During laparoscopy, fluorescence intensity was assessed. In one human cadaver, FOSC was used to mark a site on the stomach and on the sigmoid colon, respectively. Intraoperative detection during NIR laparoscopy was assessed.

Results
Gastric and colonic ICG tattooing and OSC markings were easily visible using NIR laparoscopy on T0. All FOSC were visible at T1 and T2 in both stomach and colon, whereas the ICG tattooing at T1 was only visible in the stomach of 2 animals and in the colon of 3 animals. At T2, tattoos were not visible in any animal. FOSC were still visible in both stomach and colon of the human cadaver at 10 days.

Conclusion
Endoscopic marking using FOSC can be an efficient and durable alternative to standard methods.
Interim safety analysis of the first-in-human clinical trial of the Versius surgical system, a new robot-assisted device for use in minimal access surgery
Authors: Kelkar Dhananjay , Borse Mahindra A. , Godbole Girish P. , Kurlekar Utkrant , Slack Mark 
Published: September 2020

AbstractObjectiveThe aim of this study was to provide an interim safety analysis of the first 30 surgical procedures performed using the Versius Surgical System.BackgroundRobot-assisted laparoscopy has been developed to overcome some of the important limitations of conventional laparoscopy. The new system is currently undergoing a first-in-human prospective clinical trial to confirm the safety and effectiveness of the device when performing minimal access surgery (MAS).MethodsProcedures were performed using Versius by a lead surgeon supported by an operating room (OR) team. Male or female patients aged between 18 and 65 years old and requiring elective minor or intermediate gynaecological or general surgical procedures were enrolled. The primary endpoint was the rate of unplanned conversion of procedures to other MAS or open surgery.ResultsThe procedures included nine cholecystectomies, six robot-assisted total laparoscopic hysterectomies, four appendectomies, five diagnostic laparoscopy cases, two oophorectomies, two fallopian tube recanalisation procedures, an ovarian cystectomy and a salpingo-oophorectomy procedure. All procedures were completed successfully without the need for conversion to MAS or open surgery. No patient returned to the OR within 24 h of surgery and readmittance rate at 30 and 90 days post-surgery was 1/30 (3.3%) and 2/30 (6.7%), respectively.ConclusionsThis first-in-human interim safety analysis demonstrates that the Versius Surgical System is safe and can be used to successfully perform minor or intermediate gynaecological and general surgery procedures. The cases presented here provide evidence that the Versius clinical trial can continue to extend recruitment and begin to include major procedures, in alignment with the IDEAL-D Framework Stage 2b: Exploration.
Long-Term Impact of Liming on Soil C and N in a Fertile Spruce Forest Ecosystem
Authors: Persson T. , Andersson S. , Bergholm J. , Grönqvist T. , Högbom L. , Vegerfors B. , Wirén A. 
Published: September 2020

AbstractLiming can counteract acidification in forest soils, but the effects on soil C and N pools and fluxes over long periods are less well understood. Replicated plots in an acidic and N-rich 40-year-old Norway spruce (Picea abies) forest in SW Sweden (Hasslöv) were treated with 0, 3.45 and 8.75 Mg ha−1of dolomitic lime (D0, D2 and D3) in 1984. Between 1984 and 2016, soil organic C to 30 cm depth increased by 28 Mg ha−1(30% increase) in D0 and decreased by 9 Mg ha−1(9.4% decrease) in D3. The change in D2 was not significant (+ 2 Mg ha−1). Soil N pools changed proportionally to those in soil C pools. The C and N changes occurred almost exclusively in the top organic layer. Non-burrowing earthworms responded positively to liming and stimulated heterotrophic respiration in this layer in both D2 and D3. Burrowing earthworms in D3 further accelerated C and N turnover and loss of soil. The high soil C and N loss at our relatively N-rich site differs from studies of N-poor sites showing no C and N loss. Earthworms need both high pH and N-rich food to reach high abundance and biomass. This can explain why liming of N-rich soils often results in decreasing C and N pools, whereas liming of N-poor soils with few earthworms will not show any change in soil C and N. Extractable nitrate N was always higher in D3 than in D2 and D0. After 6 years (1990), potential nitrification was much higher in D3 (197 kg N ha−1) than in D0 (36 kg N ha−1), but this difference decreased during the following years, when also the unlimed organic layers showed high nitrification potential. Our experiment finds that high-dose liming of acidic N-rich forest soils produces an initial pulse of soil heterotrophic respiration and increases in earthworm biomass, which together cause long-term declines in soil C and N pools.
In Vitro Calcification of Bioprosthetic Heart Valves: Test Fluid Validation on Prosthetic Material Samples
Authors: Kiesendahl N. , Schmitz C. , Menne M. , Schmitz-Rode T. , Steinseifer U. 
Published: September 2020

AbstractCalcification is a major failure mode of bioprosthetic heart valves. So far, cost and time saving in vitro analyses of calcification potentials are unreliable, mostly due to superficial or spontaneous precipitation of the applied fluids. In this study, we developed a near-physiological non-spontaneously precipitating fluid for an accelerated in vitro calcification assessment, and validated it by analyzing the calcification potential of two prosthetic materials within two reference-tests. The first test focused on the comparison of four calcification fluids under dynamic contact with n=12 commercial bovine pericardium patches. The second one focused on the validation of the most appropriate fluid by analyzing the calcification potential of pericardium vs. polyurethane. The patches were mounted in separate test compartments and treated simultaneously with the respective fluids at an accelerated test frequency. Calcification propensity and progression were detected macroscopically and microscopically. Structural analyses of all deposits indicated hydroxyapatite by X-ray powder diffraction, which is also most commonly observed in vivo. Histological examination by von Kossa staining showed matrix internal and superficial calcifications, depending on the fluid composition. The present study reveals promising results towards the development of a meaningful, cost and time saving in vitro analysis of the calcification potential of bioprosthetic heart valves.
Predicting Academic Outcomes: A Survey from 2007 Till 2018
Authors: Alturki Sarah , Hulpuș Ioana , Stuckenschmidt Heiner 
Published: September 2020

AbstractThe tremendous growth of educational institutions’ electronic data provides the opportunity to extract information that can be used to predict students’ overall success, predict students’ dropout rate, evaluate the performance of teachers and instructors, improve the learning material according to students’ needs, and much more. This paper aims to review the latest trends in predicting students’ performance in higher education. We provide a comprehensive background for understanding Educational Data Mining (EDM). We also explain the measures of determining academic success and highlight the strengths and weaknesses of the most common data mining (DM) tools and methods used nowadays. Moreover, we provide a rich literature review of the EDM work that has been published during the past 12 years (2007–2018) with focus on the prediction of academic performance in higher education. We analyze the most commonly used features and methods in predicting academic achievement, and highlight the benefits of the mostly used DM tools in EDM. The results of this paper could assist researchers and educational planners who are attempting to carry out EDM solutions in the domain of higher education as we highlight the type of features that the previous researches found to have significant impact on the prediction, as well as the benefits and drawbacks of the DM methods and tools used for predicting academic outcomes.
Secret Hunger: The Case of Anorexia Nervosa
Authors: Giordano Simona 
Published: September 2020

AbstractAnorexia nervosa is currently classed as a mental disorder. It is considered as a puzzling condition, scarcely understood and recalcitrant to treatment. This paper reviews the main hypotheses relating to the aetiology of anorexia nervosa. In particular, it focuses on family and sociological studies of anorexia. By reflecting on the hypotheses provided within these domains, and on the questions that these studies leave unanswered, this paper suggests that anorexic behaviour is understandable and rational, if seen in light of ordinary moral values.
Ambitious subsidy reform by the WTO presents opportunities for ocean health restoration
Authors: Costello Christopher , Millage Katherine , Eisenbarth Sabrina , Galarza Elsa , Ishimura Gakushi , Rubino Laura Lea , Saccomanno Vienna , Sumaila U. Rashid , Strauss Kent 
Published: September 2020

AbstractThe World Trade Organization (WTO) is in a unique position to deliver on Sustainable Development Goal (SDG) 14.6 by reforming global fisheries subsidies in 2020. Yet, a number of unanswered questions threaten to inhibit WTO delegates from crafting a smart agreement that improves global fisheries health. We combine global data on industrial fishing activity, subsidies, and stock assessments to show that: (1) subsidies prop up fishing effort all across the world’s ocean and (2) larger subsidies tend to occur in fisheries that are poorly managed. When combined, this evidence suggests that subsidy reform could have geographically-extensive consequences for many of the world’s largest fisheries. While much work remains to establish causality and make quantitative predictions, this evidence informs the rapidly-evolving policy debate and we conclude with actionable policy suggestions.
Cryogenic Materials and Circuit Integration for Quantum Computers
Authors: Chien Wei-Chen , Jhan Shun-Jhou , Chiu Kuei-Lin , Liu Yu-xi , Kao Eric , Chang Ching-Ray 
Published: September 2020

AbstractOver the last decade, quantum computing has experienced significant changes and captured worldwide attention. In particular, superconducting qubits have become the leading candidates for scalable quantum computers, and a number of cryogenic materials have scientifically demonstrated their potential uses in constructing qubit chips. However, because of insufficient coherence time, establishing a robust and scalable quantum platform is still a long-term goal. Another consideration is the control circuits essential to initializing, operating and measuring the qubits. To keep noise low, control circuits in close proximity to the qubits require superior reliability in the cryogenic environment. The realization of the quantum advantage demands qubits with appropriate circuitry designs to maintain long coherence times and entanglement. In this work, we briefly summarize the current status of cryogenic materials for qubits and discuss typical cryogenic circuitry designs and integration techniques for qubit chips. In the end, we provide an assessment of the prospects of quantum computers and some other promising cryogenic materials.