bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing machine-learning models for mutagenicity prediction through better feature selection
Authors: Shinada Nicolas K , Koyama Naoki , Ikemori Megumi , Nishioka Tomoki , Hitaoka Seiji , Hakura Atsushi , Asakura Shoji , Matsuoka Yukiko , Palaniappan Sucheendra K 
Published: April 2022

Abstract
Assessing a compound’s mutagenicity using machine learning is an important activity in the drug discovery and development process. Traditional methods of mutagenicity detection, such as Ames test, are expensive and time and labor intensive. In this context, in silico methods that predict a compound mutagenicity with high accuracy are important. Recently, machine-learning (ML) models are increasingly being proposed to improve the accuracy of mutagenicity prediction. While these models are used in practice, there is further scope to improve the accuracy of these models. We hypothesize that choosing the right features to train the model can further lead to better accuracy. We systematically consider and evaluate a combination of novel structural and molecular features which have the maximal impact on the accuracy of models. We rigorously evaluate these features against multiple classification models (from classical ML models to deep neural network models). The performance of the models was assessed using 5- and 10-fold cross-validation and we show that our approach using the molecule structure, molecular properties, and structural alerts as feature sets successfully outperform the state-of-the-art methods for mutagenicity prediction for the Hansen et al. benchmark dataset with an area under the receiver operating characteristic curve of 0.93. More importantly, our framework shows how combining features could benefit model accuracy improvements.
Convergence of SIRT1 and ATR signaling to modulate replication origin dormancy
Authors: Thakur Bhushan L , Baris Adrian M , Fu Haiqing , Redon Christophe E , Pongor Lorinc S , Mosavarpour Sara , Gross Jacob M , Jang Sang-Min , Sebastian Robin , Utani Koichi , Jenkins Lisa M , Indig Fred E , Aladjem Mirit I 
Published: April 2022

Abstract
During routine genome duplication, many potential replication origins remain inactive or ‘dormant’. Such origin dormancy is achieved, in part, by an interaction with the metabolic sensor SIRT1 deacetylase. We report here that dormant origins are a group of consistent, pre-determined genomic sequences that are distinguished from baseline (i.e. ordinarily active) origins by their preferential association with two phospho-isoforms of the helicase component MCM2. During normal unperturbed cell growth, baseline origins, but not dormant origins, associate with a form of MCM2 that is phosphorylated by DBF4-dependent kinase (DDK) on serine 139 (pS139-MCM2). This association facilitates the initiation of DNA replication from baseline origins. Concomitantly, SIRT1 inhibits Ataxia Telangiectasia and Rad3-related (ATR)-kinase-mediated phosphorylation of MCM2 on serine 108 (pS108-MCM2) by deacetylating the ATR-interacting protein DNA topoisomerase II binding protein 1 (TOPBP1), thereby preventing ATR recruitment to chromatin. In cells devoid of SIRT1 activity, or challenged by replication stress, this inhibition is circumvented, enabling ATR-mediated S108-MCM2 phosphorylation. In turn, pS108-MCM2 enables DDK-mediated phosphorylation on S139-MCM2 and facilitates replication initiation at dormant origins. These observations suggest that replication origin dormancy and activation are regulated by distinct post-translational MCM modifications that reflect a balance between SIRT1 activity and ATR signaling.
Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial
Authors: Omuro Antonio , Brandes Alba A , Carpentier Antoine F , Idbaih Ahmed , Reardon David A , Cloughesy Timothy , Sumrall Ashley , Baehring Joachim , van den Bent Martin , Bähr Oliver , Lombardi Giuseppe , Mulholland Paul , Tabatabai Ghazaleh , Lassen Ulrik , Sepulveda Juan Manuel , Khasraw Mustafa , Vauleon Elodie , Muragaki Yoshihiro , Di Giacomo Anna Maria , Butowski Nicholas , Roth Patrick , Qian Xiaozhong , Fu Alex Z , Liu Yanfang , Potter Von , Chalamandaris Alexandros-Georgios , Tatsuoka Kay , Lim Michael , Weller Michael 
Published: April 2022

Abstract

Background
Addition of temozolomide (TMZ) to radiotherapy (RT) improves overall survival (OS) in patients with glioblastoma (GBM), but previous studies suggest that patients with tumors harboring an unmethylated MGMT promoter derive minimal benefit. The aim of this open-label, phase III CheckMate 498 study was to evaluate the efficacy of nivolumab (NIVO) + RT compared with TMZ + RT in newly diagnosed GBM with unmethylated MGMT promoter.

Methods
Patients were randomized 1:1 to standard RT (60 Gy) + NIVO (240 mg every 2 weeks for eight cycles, then 480 mg every 4 weeks) or RT + TMZ (75 mg/m2 daily during RT and 150–200 mg/m2/day 5/28 days during maintenance). The primary endpoint was OS.

Results
A total of 560 patients were randomized, 280 to each arm. Median OS (mOS) was 13.4 months (95% CI, 12.6 to 14.3) with NIVO + RT and 14.9 months (95% CI, 13.3 to 16.1) with TMZ + RT (hazard ratio [HR], 1.31; 95% CI, 1.09 to 1.58; P = .0037). Median progression-free survival was 6.0 months (95% CI, 5.7 to 6.2) with NIVO + RT and 6.2 months (95% CI, 5.9 to 6.7) with TMZ + RT (HR, 1.38; 95% CI, 1.15 to 1.65). Response rates were 7.8% (9/116) with NIVO + RT and 7.2% (8/111) with TMZ + RT; grade 3/4 treatment-related adverse event (TRAE) rates were 21.9% and 25.1%, and any-grade serious TRAE rates were 17.3% and 7.6%, respectively.

Conclusions
The study did not meet the primary endpoint of improved OS; TMZ + RT demonstrated a longer mOS than NIVO + RT. No new safety signals were detected with NIVO in this study. The difference between the study treatment arms is consistent with the use of TMZ + RT as the standard of care for GBM.
ClinicalTrials.gov NCT02617589
Role of shift work in dietary changes among Danish nurses
Authors: Martyn Y , McElvenny D 
Published: April 2022

Abstract

Background
Research indicates that shift work is associated with dietary changes and the development of chronic diseases.

Aims
To assess if moving from day work into shift work is associated with dietary changes in Danish nurses.

Methods
Binary variables of changes in food consumption were created using data from the 1993 and 1999 surveys of the Danish Nurse Cohort. Analyses were carried out using multiple logistic regression in SPSS to assess how dietary practices changed in nurses who moved from day work into shift work compared with those who remained in day work.

Results
This study included 763 nurses who changed from Day to Shift work and 4022 nurses who continued to work days. Nurses who moved from day work into shift work were more likely to decrease their potato and vegetable intake odds ratio (OR) 1.31 (1.04–1.63). There was no difference in the frequency of coffee, milk or cheese consumption. New shift workers consumed more fatty meat OR 1.82 (1.23–2.69), sausages OR 1.37 (1.09–1.73) and cream/whipped cream/butter OR 1.61 (1.25–2.07) when they had avoided these foods in the past, compared to those who remained in day work.

Conclusions
The majority of Danish nurses made little change to their diet as a result of moving into shift work, but some made dietary changes that were generally unhealthy compared with those who remained in day work. Employers of nurses should consider implementing health promotional activities, facilitating access and/or providing healthy eating options in nurses moving from Day to Shift work.
Phase II Study of Ramucirumab Plus Irinotecan Combination Therapy as Second-Line Treatment in Patients with Advanced Gastric Cancer: HGCSG1603
Authors: Kawamoto Yasuyuki , Yuki Satoshi , Sawada Kentaro , Nakamura Michio , Muto Osamu , Sogabe Susumu , Shindo Yoshiaki , Ishiguro Atsushi , Sato Atsushi , Tsuji Yasushi , Dazai Masayoshi , Okuda Hiroyuki , Meguro Takashi , Harada Kazuaki , Sekiguchi Mari , Okada Kazufumi , Ito Yoichi M , Sakata Yuh , Sakamoto Naoya , Komatsu Yoshito 
Published: April 2022

Abstract

Background
Ramucirumab is a human IgG1 monoclonal vascular endothelial growth factor receptor-2 antibody that inhibits tumor cell growth and affects the tumor cell microenvironment. We assessed the efficacy and safety of ramucirumab plus irinotecan combination therapy as second-line treatment in patients with previously treated advanced gastric cancer.

Materials and Methods
Patients with advanced gastric cancer refractory or intolerant to primary chemotherapy were included. Ramucirumab 8 mg/kg plus irinotecan 150 mg/m2 combination therapy was administered every 2 weeks. The primary endpoint was progression-free survival rate at 6 months and secondary endpoints were overall survival, progression-free survival, response rate, safety, and dose intensity for each drug.

Results
Thirty-five patients were enrolled between January 2018 and September 2019. The progression-free survival rate at 6 months was 26.5% [95%CI, 13.2%–41.8%, P = .1353)]. Median progression-free and overall survivals were 4.2 months (95%CI, 2.5-5.4 months) and 9.6 months (95%CI, 6.4-16.6 months), respectively. The overall response rate was 25.9% (95%CI, 11.1-36.3%) and disease control rate was 85.2% (95%CI, 66.3-95.8%). Grade ≥3 adverse events that occurred in &gt;10% of patients included neutropenia, leucopenia, anemia, anorexia, and febrile neutropenia. No death or new safety signals with a causal relation to the study treatment were observed.

Conclusion
Although the primary endpoint was not achieved statistically, combination therapy of ramucirumab plus irinotecan showed anticancer activity and a manageable safety profile for second-line treatment of patients with advanced gastric cancer.
How to solve big problems: bespoke versus platform strategies
Authors: Ansar Atif , Flyvbjerg Bent 
Published: April 2022

Abstract
How should government and business leaders solve big problems? Ought policy responses to occur in bold leaps or multitudinous methodical moves? Here we show that one-off major projects, with a high level of bespoke content, are prone systematically to poorer outcomes than projects built with a repeatable platform strategy. Repeatable projects are cheaper, faster, and scale in volume and variety at much lower risk of failure. We arrive at these conclusions using comparative evidence—NASA vs SpaceX—on cost, speed-to-market and schedule, and scalability outcomes of their respective space missions. Our reference class dataset consists of 203 space missions spanning 1963–2021, of which 181 missions belong to NASA and 22 belong to SpaceX. We find that SpaceX’s platform strategy was 10X cheaper and 2X faster than NASA’s bespoke strategy. Moreover, SpaceX’s platform strategy was less risky, virtually eliminating cost overruns. We further show that achieving platform repeatability is a strategically diligent process involving experimental learning sequences. Sectors of the economy where governments find it difficult to control spending or timeframes or to get benefits quickly enough—e.g. health, education, climate, defence—are ripe for a platform rethink.
The Future of Parliamentary and Legislative Studies
Authors: Crewe Emma , Taylor-Robinson Michelle M , Martin Shane 
Published: April 2022

Abstract
In this article, Emma Crewe, Michelle M. Taylor-Robinson and Shane Martin discuss the future of parliamentary and legislative studies. The exchange is based on a Roundtable on the past, present and future of parliamentary studies, which was held online on 9 June 2021 as part of the Annual Conference of the UK Political Studies Association’s Parliaments Specialist Group.
ThePresentof Parliamentary and Legislative Studies
Authors: Taylor-Robinson Michelle M , Crewe Emma , Martin Shane 
Published: April 2022

AbstractIn this article, Michelle M. Taylor-Robinson, Emma Crewe and Shane Martin discuss the present of parliamentary and legislative studies. The exchange is based on a Roundtable on the past, present and future of parliamentary studies, which was held online on 9 June 2021 as part of the Annual Conference of the UK Political Studies Association’s Parliaments Specialist Group.
COVID-19 Vaccination Passports: Are They a Threat to Equality?
Authors: Voigt Kristin 
Published: April 2022

Abstract
In several countries, governments have implemented so-called ‘COVID passport’ schemes, which restrict access to venues such as bars or sports events to those who are vaccinated against COVID-19 and/or exempt vaccinated individuals from public health measures such as curfews or quarantine requirements. These schemes have been the subject of a heated debate. Concerns about inequality have played an important role in the opposition to such schemes. This article highlights that determining how COVID passports affect equality requires a much more nuanced analysis than is typically assumed. I identify a range of broadly egalitarian considerations that could be affected by the introduction of COVID passport schemes. While these schemes could undermine certain aspects of equality, I argue that they could also be used to promote equality. The magnitude and severity of these different effects, both promoting and undermining equality, depend on how precisely these schemes are framed and the local context in which they are implemented.
Quantitation of SARS-CoV-2 neutralizing antibodies with a virus-free, authentic test
Authors: Roessler Johannes , Pich Dagmar , Albanese Manuel , Wratil Paul R , Krähling Verena , Hellmuth Johannes C , Scherer Clemens , von Bergwelt-Baildon Michael , Becker Stephan , Keppler Oliver T , Brisson Alain , Zeidler Reinhard , Hammerschmidt Wolfgang 
Published: April 2022

AbstractNeutralizing antibodies (NAbs), and their concentration in sera of convalescents and vaccinees are a correlate of protection from COVID-19. The antibody concentrations in clinical samples that neutralize SARS-CoV-2 are difficult and very cumbersome to assess with conventional virus neutralization tests (cVNTs), which require work with the infectious virus and biosafety level 3 containment precautions. Alternative virus neutralization tests (VNTs) currently in use are mostly surrogate tests based on direct or competitive enzyme immunoassays or use viral vectors with the spike protein as the single structural component of SARS-CoV-2. To overcome these obstacles, we developed a virus-free, safe and very fast (4.5 h) in vitro diagnostic test based on engineered yet authentic SARS-CoV-2 virus-like particles (VLPs). They share all features of the original SARS-CoV-2 but lack the viral RNA genome, and thus are noninfectious. NAbs induced by infection or vaccination, but also potentially neutralizing monoclonal antibodies can be reliably quantified and assessed with ease and within hours with our test, because they interfere and block the ACE2-mediated uptake of VLPs by recipient cells. Results from the VLP neutralization test (VLPNT) showed excellent specificity and sensitivity and correlated very well with a cVNT using fully infectious SARS-CoV-2. The results also demonstrated the reduced neutralizing capacity of COVID-19 vaccinee sera against variants of concern of SARS-CoV-2 including omicron B.1.1.529, BA.1.
A Method for Organized Crime Harm Assessment: Connecting Associated Crimes
Authors: Gómez-Quintero Juliana , Chainey Spencer , Borrion Hervé 
Published: April 2022

AbstractThe increasing call for harm-focused approaches warrants a method for assessing the harm of organized crime. A harm assessment of organized crime can be of use to law enforcement agencies for prioritizing efforts and designing policies that aim to counter organized crimes based on the harm they cause. It can also be used by other institutions that can intervene and support law enforcement indirectly in preventing and counteracting organized crime. However, assessing the harm of organized crime entails dealing with the complex structure of intertwined criminal activities and addressing the fact that organized crime groups commit other crimes to support their main criminal activity. This research introduces a novel method for Organized Crime Harm Assessment (OCHA method) and demonstrates it with the application to the case of heroin trade into and within England and Wales. The challenges of applying the OCHA method are identified and discussed, as well as its limitations, contributions, and opportunities for future research.
Anti-mafia Cross-border: Conceptual and Procedural Asymmetries in the Fight against Italian Mafias in Europe
Authors: Sergi Anna , Rizzuti Alice 
Published: April 2022

Abstract
This article explores some of the challenges to fighting against Italian mafias and mafia-type organized crime in Europe, specifically in eight countries—Germany, Switzerland, the Netherlands, Belgium, Spain, Romania, the UK, and Italy. Data have been collected and analysed in two phases: first, from open sources (including media and official reports) and judicial files; secondly, from 40 individual or collective interviews. European institutions still struggle to counter the mobility of Italian mafias because of conceptual asymmetries in policing mafia-type crimes/groups and procedural challenges. We present two analytical foci: first, the existence of a conceptual tension in the definition of mafia and mafia mobility between Italy and European countries and institutions; second, emerging procedural asymmetries in countering mafias across borders, which relate more broadly to cross-border countering of organized crime. This article wishes to screenshot the state of the art and advance some reflections, without pushing any specific theoretical framework. After exploring the two main analytical foci emerging in this research, we advance recommendations.
Police Shootings in New Zealand and England and Wales: A Cross-National Comparison
Authors: Hendy Ross , Walton Darren 
Published: April 2022

AbstractIn this study, we compare the rates of New Zealand (NZ) and England and Wales (EW) police shootings from 1970 to 2020. Taking this long view lessens the stochastic effect of shootings over shorter time periods and reveals that the frequency of police shootings has increased in both jurisdictions over this period, despite police not being routinely armed with firearms. In EW, police shootings have increased from an average of 1.4 persons shot per annum for the decade ending 1980 to 4.3 per annum for the decade ending 2020. Similarly, NZ has seen an increase of 0.3 persons shot per annum (decade ending 1980) to 3.7 per annum (decade ending 2020). When comparing the rate of persons shot per million population in the past two decades, NZ has doubled the rate of shootings from 0.360 per million (2001–10) to 0.783 per million (2011–20). Such an increase has not occurred in EW as the number of persons shot has decreased from 0.080 per million (2001–10) to 0.074 per million (2011–20). We highlight the time-series trajectories with trend breakpoints at points of known policy implementations.
Possibility of a multi-step electroweak phase transition in the two-Higgs doublet models
Authors: Aoki Mayumi , Komatsu Takatoshi , Shibuya Hiroto 
Published: April 2022

Abstract
We discuss whether a multi-step electroweak phase transition (EWPT) occurs in two-Higgs doublet models (2HDMs). The EWPT is related to interesting phenomena such as baryogenesis and the ensuing gravitational wave. We examine parameter regions in CP-conserving 2HDMs and find certain areas where multi-step EWPTs occur. The parameter search shows the multi-step EWPT prefers the scalar potential with the approximate Z2 symmetry and a mass hierarchy between the neutral CP-odd and CP-even extra scalar bosons mA &lt; mH. By contrast, the multi-step EWPT whose first step is strongly first order favors a mass hierarchy mA &gt; mH. In addition, we compute the Higgs trilinear coupling in the parameter region where multi-step EWPTs occur, which can be observed at future colliders. We also discuss a multi-peaked gravitational wave from a multi-step EWPT. Subject index B53, B59
Perfect state transfer in two dimensions and the bivariate dual-Hahn polynomials
Authors: Miki Hiroshi , Tsujimoto Satoshi , Vinet Luc 
Published: April 2022

Abstract
A new solvable two-dimensional spin lattice model defined on a regular grid of triangular shape is proposed. The hopping amplitudes between sites are related to recurrence coefficients of certain bivariate dual-Hahn polynomials. For a specific choice of the parameters, perfect state transfer and fractional revival are shown to take place.
The SIT-PT Trial Protocol: A Dose-Matched Randomized Clinical Trial Comparing 2 Physical Therapist Interventions for Infants and Toddlers With Cerebral Palsy
Authors: Dusing Stacey C , Harbourne Regina T , Hsu Lin-Ya , Koziol Natalie A , Kretch Kari , Sargent Barbara , Jensen-Willett Sandra , McCoy Sarah Westcott , Vanderbilt Douglas L 
Published: April 2022

Abstract

Objective
Although early intervention for infants at risk for cerebral palsy is routinely recommended, the content of intervention is poorly described, varies widely, and has mixed supporting evidence. The purpose of this study was to compare efficacy of 2 interventions grounded in differing domains of the International Classification of Functioning, Disability and Health on developmental outcomes of infants with or at high risk of cerebral palsy.

Methods
Infants who meet inclusion criteria will be randomized into either Sitting Together and Reaching To Play or Movement, Orientation, Repetition, Exercise Physical Therapy groups. Both groups will receive intervention twice weekly for 3 months and follow-up at 3, 6, 9, and 12 months from baseline. The primary objectives compare changes over time and between groups in sitting, gross motor, and cognitive development. The setting is the infant’s home unless the caregiver requests otherwise. One hundred and fifty infants between 8 and 24 months of age will be enrolled in 3 geographically, racially, and ethnically diverse sites: Los Angeles, California; Omaha, Nebraska; and Seattle, Washington. Enrolled infants will demonstrate motor delays, emerging sitting skills, and signs of neurologic impairment. Sitting Together and Reaching To Play targets activities including sitting, reaching, and motor-based problem solving to improve global development. In contrast, Movement, Orientation, Repetition, Exercise Physical Therapy focuses on strengthening and musculoskeletal alignment while encouraging repeated movement practice. Outcome measures include the Gross Motor Function Measure, Bayley Scales of Infant Development-IV, Assessment of Problem Solving in Play, and a Parent Child Interaction assessment. Enrolled children will maintain usual intervention services due to ethical concerns with intervention withdrawal.

Impact
This will be the first study, to our knowledge, comparing efficacy of early physical therapy with dose-matched interventions and well-defined key principles. The outcomes will inform selection of key principle of intervention in this population.