bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug design targeting active posttranslational modification protein isoforms
Authors: Meng Fanwang , Liang Zhongjie , Zhao Kehao , Luo Cheng 
Published: December 2020

AbstractModern drug design aims to discover novel lead compounds with attractable chemical profiles to enable further exploration of the intersection of chemical space and biological space. Identification of small molecules with good ligand efficiency, high activity, and selectivity is crucial toward developing effective and safe drugs. However, the intersection is one of the most challenging tasks in the pharmaceutical industry, as chemical space is almost infinity and continuous, whereas the biological space is very limited and discrete. This bottleneck potentially limits the discovery of molecules with desirable properties for lead optimization. Herein, we present a new direction leveraging posttranslational modification (PTM) protein isoforms target space to inspire drug design termed as “Post‐translational Modification Inspired Drug Design (PTMI‐DD).” PTMI‐DD aims to extend the intersections of chemical space and biological space. We further rationalized and highlighted the importance of PTM protein isoforms and their roles in various diseases and biological functions. We then laid out a few directions to elaborate the PTMI‐DD in drug design including discovering covalent binding inhibitors mimicking PTMs, targeting PTM protein isoforms with distinctive binding sites from that of wild‐type counterpart, targeting protein‐protein interactions involving PTMs, and hijacking protein degeneration by ubiquitination for PTM protein isoforms. These directions will lead to a significant expansion of the biological space and/or increase the tractability of compounds, primarily due to precisely targeting PTM protein isoforms or complexes which are highly relevant to biological functions. Importantly, this new avenue will further enrich the personalized treatment opportunity through precision medicine targeting PTM isoforms.
Toward data‐efficient learning: A benchmark for COVID‐19 CT lung and infection segmentation
Authors: Ma Jun , Wang Yixin , An Xingle , Ge Cheng , Yu Ziqi , Chen Jianan , Zhu Qiongjie , Dong Guoqiang , He Jian , He Zhiqiang , Cao Tianjia , Zhu Yuntao , Nie Ziwei , Yang Xiaoping 
Published: December 2020

PurposeAccurate segmentation of lung and infection in COVID‐19 computed tomography (CT) scans plays an important role in the quantitative management of patients. Most of the existing studies are based on large and private annotated datasets that are impractical to obtain from a single institution, especially when radiologists are busy fighting the coronavirus disease. Furthermore, it is hard to compare current COVID‐19 CT segmentation methods as they are developed on different datasets, trained in different settings, and evaluated with different metrics.MethodsTo promote the development of data‐efficient deep learning methods, in this paper, we built three benchmarks for lung and infection segmentation based on 70 annotated COVID‐19 cases, which contain current active research areas, for example, few‐shot learning, domain generalization, and knowledge transfer. For a fair comparison among different segmentation methods, we also provide standard training, validation and testing splits, evaluation metrics and, the corresponding code.ResultsBased on the state‐of‐the‐art network, we provide more than 40 pretrained baseline models, which not only serve as out‐of‐the‐box segmentation tools but also save computational time for researchers who are interested in COVID‐19 lung and infection segmentation. We achieve average dice similarity coefficient (DSC) scores of 97.3%, 97.7%, and 67.3% and average normalized surface dice (NSD) scores of 90.6%, 91.4%, and 70.0% for left lung, right lung, and infection, respectively.ConclusionsTo the best of our knowledge, this work presents the first data‐efficient learning benchmark for medical image segmentation, and the largest number of pretrained models up to now. All these resources are publicly available, and our work lays the foundation for promoting the development of deep learning methods for efficient COVID‐19 CT segmentation with limited data.
Psychometric properties of the Norwegian version of the clinical learning environment comparison survey
Authors: Olaussen Camilla , Jelsness‐Jørgensen Lars‐Petter , Tvedt Christine Raaen , Hofoss Dag , Aase Ingunn , Steindal Simen A. 
Published: December 2020

AbstractAimTo translate The Clinical Learning Environment Comparison Survey (CLECS) into Norwegian and to evaluate the psychometric properties of the Norwegian version.DesignA cross‐sectional survey including a longitudinal component.MethodsThe CLECS was translated into Norwegian following the World Health Organization guidelines, including forward translation, expert panel, back‐translation, pre‐testing and cognitive interviewing. Nursing students at a Norwegian university college were invited to participate in the study (psychometrical testing) based on informed consent. Reliability and validity of the translated version of CLECS were investigated using a confirmatory factor analysis (CFA), Cronbach's alpha and test–retest analysis.ResultsA total of 122 nursing students completed the questionnaire and Cronbach alphas for the CLECS subscales ranged from 0.69 to 0.89. CFA goodness‐of‐fit indices (χ2/df = 1.409, CFI = 0.915, RMSEA = 0.058) showed acceptable model fit. Test–retest ICC ranged from 0.55 to 0.75, except for two subscales with values below 0.5
Retinoblastoma management in 13q deletion syndrome patients using super‐selective chemotherapies and other cancer‐directed interventions
Authors: Cobbs Lucy V. , Francis Jasmine H. , Dunkel Ira J. , Gobin Y. Pierre , Brodie Scott E. , Abramson David H. 
Published: December 2020

AbstractBackgroundThis study aimed to identify best practices for treating 13q deletion syndrome (13q−) patients with retinoblastoma in the era of super‐selective ophthalmic artery chemosurgery (OAC) and intravitreal injection therapy (IVIT).MethodsRetrospective study of 21 eyes from 14 patients with retinoblastoma and 13q− who were treated at Memorial Sloan Kettering Cancer Center (MSKCC) between May 2006 and May 2020, with a mean follow up of 3.7 years. Ocular survival, patient survival, and treatment toxicities were assessed.ResultsNine of the 12 eyes that underwent OAC/IVIT at MSKCC have been progression free for at least 1 year since their last treatments. Fifteen out of 26 OAC cycles resulted in grade 3‐4 hematologic toxicity. There was one death from sepsis in the setting of intravenous chemotherapy (IVC) for metastatic disease that occurred after OAC/IVIT therapy. The 2‐year Kaplan‐Meier ocular survival estimate for the whole cohort was 75% and for the eyes that received OAC or IVIT at MSKCC 83%. For OAC hematologic toxicities, one platelet transfusion and two filgrastim doses were administered, and one patient was hospitalized for neutropenic fevers.ConclusionsThe majority of 13q− eyes treated with OAC/IVIT‐based regimens can be cured, and there were no deaths related to complications from OAC or IVIT. 13q− Patients did have increased risk of systemic treatment complications, even from super‐selective chemotherapies. Despite these toxicities, only one patient developed febrile neutropenia, one patient required a blood product transfusion, and two patients received filgrastim for both OAC and IVC complications.PrécisChildren with 13q deletion syndrome with retinoblastoma managed with intra‐arterial and intravitreal chemotherapy have excellent patient and ocular survival with acceptable toxicity.
How to be successful in an academic interview in pediatric oncology: A survey of Children's Oncology Group (COG) and International Society of Paediatric Oncology (SIOP) mentors
Authors: Bryan Gemma , Morgan Jessica E. , Dhall Girish , Esbenshade Adam J. 
Published: December 2020

AbstractBackgroundA successful academic interview has been reported as the most important factor contributing to ranking of candidates for residency. However, little published guidance exists to help a prospective oncologist or researcher give such an interview. The International Society of Paediatric Oncology (SIOP) Young Investigator (YI) Network and Children's Oncology Group (COG) YI group thus cosponsored a survey of senior investigators seeking their advice.MethodsAn electronic survey covering aspects of the academic interview of both trainees and faculty were sent to all current/past mentors serving in the COG YI mentorship program and those registered as mentors in the SIOP YI mentorship program. The responses were quantitatively and qualitatively analyzed.ResultsThe response rate was 43.7% (118/270) from 25 countries. Majority of United States (US) interviewers (86.8%) conducted interviews individually, while 74% of non‐US interviewers conducted panel interviews or both types equally (P < .001). Majority of interviewers (83.4%) at least occasionally contacted colleagues for off the record opinions on candidates, and 40.9% conducted an internet or social media search. Enthusiasm for the job (97.2%) and being a team player (95.3%) were the qualities most rated as at least moderately important, while a priority for work‐life balance (45.4%) and having interests/hobbies outside of medicine (29.2%) were considered less important. Interviewers provided interview questions, tips for candidates, and key pitfalls to avoid.DiscussionCandidates should prepare for their academic interviews in advance, be enthusiastic and honest when giving responses. Detailed guidance for those applying at different career stages and in different countries are provided.
Short‐lived peaks of stem methane emissions from mature black alder (Alnus glutinosa (L.) Gaertn.) – Irrelevant for ecosystem methane budgets?
Authors: Köhn Daniel , Günther Anke , Schwabe Ines , Jurasinski Gerald 
Published: December 2020

AbstractTree stems can be a source of the greenhouse gas methane (CH4). However, assessments of the global importance of stem CH4 emissions are complicated by a lack of research and high variability between individual ecosystems. Here, we determined the contribution of emissions from stems of mature black alder (Alnus glutinosa (L.) Gaertn.) to overall CH4 exchange in two temperate peatlands. We measured emissions from stems and soils using closed chambers in a drained and an undrained alder forest over 2 years. Furthermore, we studied the importance of alder leaves as substrate for methanogenesis in an incubation experiment. Stem CH4 emissions were short‐lived and occurred only during times of inundation at the undrained site. The drained site did not show stem emissions and the soil acted as a small CH4 sink. The contribution of stem emissions to the overall CH4 budget was below 0.3% in both sites. Our results show that mature black alder can be an intermittent source of CH4 to the atmosphere. However, the low share of stem CH4 emissions in both investigated stands indicates that this pathway may be of minor relative importance in temperate peatlands, yet strongly depend on the hydrologic regime.
Micellization through complexation of oppositely charged diblock copolymers: Effects of composition, polymer architecture, salt of different valency, and thermoresponsive block
Authors: Gioldasis Christos , Gergidis Leonidas N. , Vlahos Costas 
Published: December 2020

AbstractThe structural and electrical characteristics of polyelectrolyte complex micelles (PCMs) formed by mixing of oppositely charged double hydrophilic copolymers are studied by means of molecular dynamics simulations. In mixtures of linear diblock copolymers we found that the preferential aggregation numberNpof PCMs is a universal function of the ratioγ±of the total positive to total negative charges of the mixture. The addition of divalent salts ions induces a secondary micellization. In mixtures of copolymers bearing a common neutral thermoresponsive block, micelles with contracted corona consisting of thermoresponsive blocks and complex polyelectrolyte core are formed at low salt concentration and temperature far away the biphasic regime. At high salt concentration and temperature in the biphasic regime, reversed micelles are obtained. In equimolar mixtures of linear copolymers with miktoarm stars we found thatNpof PCMs decreases as the number of charged branches of miktoarm copolymer increases. The shape of micelles progressively changes from spherical to worm‐like with the increase of number of branches of miktoarm copolymers. Our findings are in full agreement with existing experimental and theoretical predictions and provides new and additional insights.
Controls for a nonlinear system arising in vision‐based landing of airliners
Authors: Burlion Laurent , Gibert Victor , Malisoff Michael , Mazenc Frederic 
Published: December 2020

AbstractWe use a novel backstepping method to solve a stabilization problem for a nonlinear system with delayed sampled outputs that are not accurately measured. We provide an application to a system arising in vision‐based landing of airliners that includes coupling between the lateral and longitudinal dynamics, for which we provide performance guarantees in the presence of the delay, nonlinearity, and sampling. Our major contributions are (a) designs of lateral and longitudinal controls for our nonlinear model of an aircraft landing on an unequipped runway, (b) mathematical proofs that our controls ensure that the aircraft being modeled achieves desired alignment with the runway during its align phase, under sampling and delays that arise from image processing of visual information, and (c) comparative simulations exhibiting considerable improvement in control performance compared with previous methods that did not take the coupling of the dynamics or imprecise delayed sampled measurements into account.
Distributed continuous‐time constrained convex optimization with general time‐varying cost functions
Authors: Huang Bomin , Zou Yao , Meng Ziyang 
Published: December 2020

AbstractThe distributed time‐varying constrained convex optimization problem over a connected undirected network topology is studied in this article. The proposed distributed optimization algorithm is composed of a projection map term, a consensus term, and a gradient term, and is feasible for any initial condition. We first show that the states of the optimization algorithm uniformly converge to a neighborhood of the constraint set while an approximate global consensus is achieved. Then the states are proven to uniformly converge to a neighborhood of the time‐varying optimal trajectory. The theoretical results are validated by some simulations.
Stem Cells for Next Level Toxicity Testing in the 21st Century
Authors: Fritsche Ellen , Haarmann‐Stemmann Thomas , Kapr Julia , Galanjuk Saskia , Hartmann Julia , Mertens Peter R. , Kämpfer Angela A. M. , Schins Roel P. F. , Tigges Julia , Koch Katharina 
Published: December 2020

AbstractThe call for a paradigm change in toxicology from the United States National Research Council in 2007 initiates awareness for the invention and use of human‐relevant alternative methods for toxicological hazard assessment. Simple 2D in vitro systems may serve as first screening tools, however, recent developments infer the need for more complex, multicellular organotypic models, which are superior in mimicking the complexity of human organs. In this review article most critical organs for toxicity assessment, i.e., skin, brain, thyroid system, lung, heart, liver, kidney, and intestine are discussed with regards to their functions in health and disease. Embracing the manifold modes‐of‐action how xenobiotic compounds can interfere with physiological organ functions and cause toxicity, the need for translation of such multifaceted organ features into the dish seems obvious. Currently used in vitro methods for toxicological applications and ongoing developments not yet arrived in toxicity testing are discussed, especially highlighting the potential of models based on embryonic stem cells and induced pluripotent stem cells of human origin. Finally, the application of innovative technologies like organs‐on‐a‐chip and genome editing point toward a toxicological paradigm change moves into action.
Dinucleoside‐Based Macrocycles Displaying Unusually Large Chelate Cooperativities
Authors: Serrano‐Molina David , de Juan Alberto , González‐Rodríguez David 
Published: December 2020

AbstractHigh‐fidelity production of a single self‐assembled species in competition with others relies on achieving strong chelate cooperativities, which can be quantified by the effective molarity parameter. Therefore, supramolecular systems displaying very high effective molarities are reliably formed in a wide range of experimental conditions and exhibit “all‐or‐none” phenomena, meaning that the assembly is either fully formed or fully dissociated into the corresponding monomeric components. We summarize here our efforts in the study and characterization of one of these synthetic systems exhibiting record chelate cooperativities: the self‐assembly of rod‐like dinucleoside molecules into tetrameric macrocycles through hydrogen‐bonding Watson‐Crick interactions.
Harmonic hybrid inflation
Authors: Carta Federico , Righi Nicole , Welling Yvette , Westphal Alexander 
Published: December 2020

AbstractWe present a mechanism for realizing hybrid inflation using two axion fields with a purely non-perturbatively generated scalar potential. The structure of the scalar potential is highly constrained by the discrete shift symmetries of the axions. We show that harmonic hybrid inflation generates observationally viable slow-roll inflation for a wide range of initial conditions. This is possible while accommodating certain UV arguments favoring constraintsf≲MPand ∆ϕ60≲MPon the axion periodicity and slow-roll field range, respectively. We discuss controlled ℤ2-symmetry breaking of the adjacent axion vacua as a means of avoiding cosmological domain wall problems. Including a minimal form of ℤ2-symmetry breaking into the minimally tuned setup leads to a prediction of primordial tensor modes with the tensor-to-scalar ratio in the range 10−4≲r≲ 0.01, directly accessible to upcoming CMB observations. Finally, we outline several avenues towards realizing harmonic hybrid inflation in type IIB string theory.
Fertility versus productivity: a model of growth with evolutionary equilibria
Authors: Foreman-Peck James , Zhou Peng 
Published: December 2020

AbstractWe develop a quantitative model that is consistent with three principal building blocks of Unified Growth Theory: the break-out from economic stagnation, the build-up to the Industrial Revolution, and the onset of the fertility transition. Our analysis suggests that England’s escape from the Malthusian trap was triggered by the demographic catastrophes in the aftermath of the Black Death; household investment in children ultimately raised wages despite an increasing population; and rising human capital, combined with the increasing elasticity of substitution between child quantity and quality, reduced target family size and contributed to the fertility transition.
Bowel wall thickening and hyperemia assessed by high-frequency ultrasound indicate histological inflammation in Crohn’s ileitis
Authors: Goertz Ruediger S. , Hensel Stefanie , Wildner Dane , Neurath Markus F. , Strobel Deike 
Published: December 2020

Abstract
Purpose
We evaluated ileal bowel wall thickness and semiquantitative vascularization by ultrasound in correlation with the presence or absence of histopathological inflammation in patients with Crohn’s disease (CD).

Methods
We conducted a retrospective analysis of 221 ultrasound examinations of the terminal ileum or neoterminal ileum in CD patients with biopsies of the ileum during colonoscopies within 8 weeks of the ultrasound. Ultrasound data were obtained from an inflammatory bowel disease ultrasound register from 2011 to 2017. Bowel wall ultrasound was performed by a high-frequency, linear transducer (7–12 MHz). Presence of bowel wall thickening (> 3 mm), vascularization by the Limberg score, and presence of ileal histopathological inflammation were analyzed.

Results
In 221 bowel wall ultrasound examinations of CD patients (128 female, 93 male, mean age 37.5 years), a thickened bowel wall was found in 140 (63.3%) and hypervascularization (corresponding to a Limberg score ≥ 2) in 96 (43.4%) cases. In 187 (84.6%) cases, ileal inflammation was confirmed by histopathology and in 34 (15.4%) cases no inflammation was shown. Bowel wall thickening showed a sensitivity of 70.1%, a negative predictive value (NPV) of 30.9%, a specificity of 73.5% and a positive predictive value (PPV) of 93.6% for the detection of histopathological ileal inflammation. Hypervasularization had a low sensitivity (49.7%) and NPV (24.8%), but high specificity (91.2%) and PPV (96.9%).

Conclusion
In this CD subcohort of an ultrasound register, pathologic ultrasound findings were quite common. Bowel wall thickening (> 3 mm) and hypervascularization are good predictors of histopathological inflammation within the terminal ileum or neoterminal ileum. Normal ultrasound findings without bowel wall thickening and without hypervascularization do not rule out histopathological inflammation.
The effect of daily walking exercise on sleep quality in healthy young adults
Authors: Wang Feifei , Boros Szilvia 
Published: December 2020

Abstract
Purpose
Walking has beneficial effects on sleep quality in elderly population and patients in clinical settings. However, less is known whether walking improves sleep quality among healthy young adults. This study examined the effectiveness of a 12-week walking intervention on sleep quality among sedentary young adults.

Methods
Fifty-four healthy adults aged 19 to 36-years old participated a pedometer based aerobic walking intervention, a cross-over randomized control trial. Participants were assigned into two groups (group A and group B) randomly. The 12-week intervention was divided into three sessions equally. Sleep quality was assessed by Pittsburgh Sleep Quality Index (PSQI) before and after session 1 and session 3. Omron HJ-112 pedometer and daily walking diary facilitated the intervention process. Within group and between group comparisons were made for statistical analysis.

Results
Within group comparison by repeated measures showed that sleep duration (p < 0.01, F-test 22.79), sleep medication (p < 0.05, F-test 5.22), subjective sleep (p < 0.05, F-test 5.51) and global sleep quality (p < 0.01, F-test 12.19) were significantly improved. The comparison between intervention group and control group showed that sleep disturbance was significantly improved (p < 0.05).

Conclusion
Daily walking exercise has a significant effect on facilitating sleep quality and sleep components among young adults. Further studies are suggested to examine the impact of walking intensity on sleep quality.