bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venetoclax-based Rational Combinations are Effective in Models of MYCN-amplified Neuroblastoma
Authors: Dalton Krista M. , Krytska Kateryna , Lochmann Timothy L. , Sano Renata , Casey Colleen , D'Aulerio Alessia , Khan Qasim A. , Crowther Giovanna Stein , Coon Colin , Cai Jinyang , Jacob Sheeba , Kurupi Richard , Hu Bin , Dozmorov Mikhail , Greninger Patricia , Souers Andrew J. , Benes Cyril H. , Mossé Yael P. , Faber Anthony C. 
Published: June 2021

Abstract
Venetoclax is a small molecule inhibitor of the prosurvival protein BCL-2 that has gained market approval in BCL-2–dependent hematologic cancers including chronic lymphocytic leukemia and acute myeloid leukemia. Neuroblastoma is a heterogenous pediatric cancer with a 5-year survival rate of less than 50% for high-risk patients, which includes nearly all cases with amplified MYCN. We previously demonstrated that venetoclax is active in MYCN-amplified neuroblastoma but has limited single-agent activity in most models, presumably the result of other pro-survival BCL-2 family protein expression or insufficient prodeath protein mobilization. As the relative tolerability of venetoclax makes it amenable to combining with other therapies, we evaluated the sensitivity of MYCN-amplified neuroblastoma models to rational combinations of venetoclax with agents that have both mechanistic complementarity and active clinical programs. First, the MDM2 inhibitor NVP-CGM097 increases the prodeath BH3-only protein NOXA to sensitize p53-wild-type, MYCN-amplified neuroblastomas to venetoclax. Second, the MCL-1 inhibitor S63845 sensitizes MYCN-amplified neuroblastoma through neutralization of MCL-1, inducing synergistic cell killing when combined with venetoclax. Finally, the standard-of-care drug cocktail cyclophosphamide and topotecan reduces the apoptotic threshold of neuroblastoma, thus setting the stage for robust combination efficacy with venetoclax. In all cases, these rational combinations translated to in vivo tumor regressions in MYCN-amplified patient-derived xenograft models. Venetoclax is currently being evaluated in pediatric patients in the clinic, including neuroblastoma (NCT03236857). Although establishment of safety is still ongoing, the data disclosed herein indicate rational and clinically actionable combination strategies that could potentiate the activity of venetoclax in patients with amplified MYCN with neuroblastoma.
EMT-Derived Alterations in Glutamine Metabolism Sensitize Mesenchymal Breast Cells to mTOR Inhibition
Authors: Karvelsson Sigurdur Trausti , Sigurdsson Arnar , Seip Kotryna , Grinde Maria Tunset , Wang Qiong , Johannsson Freyr , Mælandsmo Gunhild Mari , Moestue Siver Andreas , Rolfsson Ottar , Halldorsson Skarphedinn 
Published: June 2021

Abstract

Epithelial-to-mesenchymal transition (EMT) is a fundamental developmental process with strong implications in cancer progression. Understanding the metabolic alterations associated with EMT may open new avenues of treatment and prevention. Here we used 13C carbon analogs of glucose and glutamine to examine differences in their utilization within central carbon and lipid metabolism following EMT in breast epithelial cell lines. We found that there are inherent differences in metabolic profiles before and after EMT. We observed EMT-dependent re-routing of the TCA-cycle, characterized by increased mitochondrial IDH2-mediated reductive carboxylation of glutamine to lipid biosynthesis with a concomitant lowering of glycolytic rates and glutamine-dependent glutathione (GSH) generation. Using weighted correlation network analysis, we identified cancer drugs whose efficacy against the NCI-60 Human Tumor Cell Line panel is significantly associated with GSH abundance and confirmed these in vitro. We report that EMT-linked alterations in GSH synthesis modulate the sensitivity of breast epithelial cells to mTOR inhibitors.

Implications:
EMT in breast cells causes an increased demand for glutamine for fatty acid biosynthesis, altering its contribution to glutathione biosynthesis, which sensitizes the cells to mTOR inhibitors.
New species of Paraodontomma from mid-Cretaceous Burmese amber with muscle tissue preservation (Coleoptera: Archostemata: Ommatidae)
Authors: Li Yan-Da , Yamamoto Shûhei , Huang Di-Ying , Cai Chen-Yang 
Published: June 2021

The third member of the extinct ommatid genus Paraodontomma is reported from mid-Cretaceous Burmese amber. Our observation confirms the transverse ridges on elytra as a diagnostic character for the genus. Paraodontomma leptocristatum sp. nov. differs from previously reported congeners mainly in head subquadrate and without prominent protuberances, pronotal disc without prominent ridges, elytral ridges indistinct, and teeth along elytral margins not forming a wavy pattern. Musculature is preserved in the newly discovered specimen of P. leptocristatum, which further demonstrates the preservation potential and irreplaceable value of amber fossils.
Sagitta otolith of three demersal species in a tropical environment
Authors: Oliveira Crismen Santana de , Freire Kátia de Meirelles Felizola , Rosa Leonardo Cruz da , Carvalho Barbara Maichak de 
Published: June 2021

The objective of this study was to describe the morphology and morphometry of saggitta otoliths of Polydactylus virginicus, Menticirrhus cuiaranensis and Conodon nobilis in a tropical environment. Fishes were caught with rod and reel in competitive fishing events promoted in 2014-2015 along the coast of Sergipe. A total of 174 pairs of sagitta otoliths of P. virginicus, 181 of M. cuiaranensis and 77 of C. nobilis was extracted. In general, the sagitta otoliths of all three species analyzed here presented different morphology and shape indices. The permutational multivariate analysis of variance (PERMANOVA) demonstrated significant differences among species and ontogenetic phases within each species using morphometry and shape indices. The linear discriminant analysis (LDA) presented a 98.3% correct reclassification of the otoliths by species.
Modern Slavery and the Law of the Sea
Authors: Kojima Chie 
Published: June 2021

Abstract
Practices of modern slavery across maritime borders, such as human trafficking and forced labour in the maritime and fishing industries, are often unregulated and uncontrolled due to legal uncertainties and the lack of political will. This article discusses possibilities to re-interpret the United Nations Convention on the Law of the Sea to give a complementary role to non-flag States in controlling modern slavery practices at sea. In particular, it analyses the question as to whether a non-flag State may take prescriptive and enforcement measures against a foreign vessel suspected of modern slavery on the high seas.
What Use Is Customary International Law?
Authors: Carty Anthony 
Published: June 2021

Abstract
Customary international law as a source of general law is given a primary place in Article 38 of the ICJ Statute. However, it is historically a concept created by legal doctrine. The very idea of custom supposes legal persons are natural persons living in a dynamic, evolving community. This was the assumption of the historical school of law in the 19th century when the concept of custom was developed. Now the dominant notion of legal personality is the State as an impersonal corporation and international legal theory (Brierly and D’Amato) can see well that the death of the historical school of law has to mean the death of the concept of custom. What should replace it? Two steps need to be taken in sequence. Firstly, following the Swedish realist philosopher Haegerstrom, we have to ascertain the precise constellations of the conflictual attitudes the populations of States have to the patterns of normativity which they project onto international society. Secondly, we should follow the virtue ethics jurisprudence of Paul Ricoeur and others, who develop a theory of critical legal doctrinal judgement, along the classical lines of Aristotle and Confucius, to challenge and sort out the prejudices of peoples into some reasonable shape, whereby these can be encouraged to understand and respect one another.
Then one will not have to endure so many silly interpretations of international law such as the one declaring that there are only rocks in the South China Sea and not islands. Such interpretations have nothing to do with the supposedly ordinary legal language analysis of a convention and the State practice surrounding it. They have to do entirely with a continued lack of respect by Western jurists for non-Western societies and nations.
The Development of International Law of the Sea by International Courts and Tribunals
Authors: Zhang Hua 
Published: June 2021

Abstract
The development of international law of the sea by international courts and tribunals is generally acknowledged among international lawyers. In retrospect, the creative jurisprudence of international judicial bodies was incorporated into the mainstream of international law-making process in many cases, while the experience of failure cannot be ignored. In the past decade, the strengthening of marine environmental protection has become a tendency in international adjudication. Accordingly, the content and scope of due diligence obligation has been discovered, consolidated and extended. In light of the evolution of due diligence obligation, the methodology of law-making by international judicial bodies includes: inter alia, interpretation, cross-reference of precedents, analogy, and assertion. However, from the perspective of legitimacy, law-making should not become the normal function of international judicial bodies. Bearing in mind international rule of law and good administration of justice, the lawmaking activities of international courts and tribunals should be curtailed in certain degree.
Hydrological evaluation of high-resolution precipitation estimates from the WRF model in the Third Pole river basins
Authors: Sun He , Su Fengge , He Zhihua , Ou Tinghai , Chen Deliang , Li Zhenhua , Li Yanping 
Published: June 2021

AbstractIn this study, two sets of precipitation estimates based on the regional Weather Research and Forecasting model (WRF) –the high Asia refined analysis (HAR) and outputs with a 9 km resolution from WRF (WRF-9km) are evaluated at both basin and point scales, and their potential hydrological utilities are investigated by driving the Variable Infiltration Capacity (VIC) large-scale land surface hydrological model in seven Third Pole (TP) basins. The regional climate model (RCM) tends to overestimate the gauge-based estimates by 20–95% in annual means among the selected basins. Relative to the gauge observations, the RCM precipitation estimates can accurately detect daily precipitation events of varying intensities (with absolute bias < 3 mm). The WRF-9km exhibits a high potential for hydrological application in the monsoon-dominated basins in the southeastern TP (with NSE of 0.7–0.9 and bias of -11% to 3%), while the HAR performs well in the upper Indus (UI) and upper Brahmaputra (UB) basins (with NSE of 0.6 and bias of -15% to -9%). Both the RCM precipitation estimates can accurately capture the magnitudes of low and moderate daily streamflow, but show limited capabilities in flood prediction in most of the TP basins. This study provides a comprehensive evaluation of the strength and limitation of RCMs precipitation in hydrological modeling in the TP with complex terrains and sparse gauge observations.
Evaluation of a land-atmosphere coupling metric computed from a ground-based infrared interferometer
Authors: Wakefield Ryann A. , Turner David D. , Basara Jeffrey B. 
Published: June 2021

AbstractLand-atmosphere feedbacks are a critical component of the hydrologic cycle. Vertical profiles of boundary layer temperature and moisture, together with information about the land surface, are used to compute land-atmosphere coupling metrics. Ground based remote sensing platforms, such as the Atmospheric Emitted Radiance Interferometer (AERI), can provide high temporal resolution vertical profiles of temperature and moisture. When co-located with soil moisture, surface flux, and surface meteorological observations, such as at the Atmospheric Radiation Measurement (ARM) Southern Great Plains (SGP) site, it is possible to observe both the terrestrial and atmospheric legs of land-atmosphere feedbacks. In this study, we compare a commonly used coupling metric computed from radiosonde-based data to that obtained from the AERI to characterize the accuracy and uncertainty in the metric derived from the two distinct platforms. This approach demonstrates the AERI’s utility where radiosonde observations are absent in time and/or space. Radiosonde and AERI based observations of the Convective Triggering Potential and Low-Level Humidity Index (CTP-HIlow) were computed during the 1200 UTC observation time and displayed good agreement during both 2017 and 2019 warm seasons. Radiosonde and AERI derived metrics diagnosed the same atmospheric preconditioning based upon the CTP-HIlow framework a majority of the time. When retrieval uncertainty was considered, even greater agreement was found between radiosonde and AERI derived classification. The AERI’s ability to represent this coupling metric well enabled novel exploration of temporal variability within the overnight period in CTP and HIlow. Observations of CTP-HIlow computed within a few hours of 1200 UTC were essentially equivalent, however with greater differences in time arose greater differences in CTP and HIlow.
Innovative work behaviors and networking across government
Authors: Demircioglu Mehmet Akif , Hameduddin Taha , Knox Colin 
Published: June 2021

Public organizations have long faced pressures to become more innovative and entrepreneurial. This has been accompanied by a shift from traditional bureaucratic structures toward public management networks, both in scholarship and practice. We use the example of the Australian public service and its emphasis on increased networking to examine whether increased networking behavior is associated with greater innovative work behaviors. In developing our theoretical model, we hypothesize that networking activities are positively related to innovative work behaviors but that too few or too many networked actors are negatively associated with innovative work behaviors. Our analysis finds that networking practices are, indeed, associated with greater levels of innovative work behaviors but that they differ between the type of stakeholders public managers engage with. In addition, we find only limited evidence of a curvilinear relationship between these two constructs. The article ends with implications for research and practice. Points for practitioners Public organizations around the world are under pressure to become more innovative and collaborative. This is especially the case in the Australian public service. One way to achieve innovation is to encourage innovative work behaviors. We find that increased networking by public managers is associated with higher levels of innovative work behaviors. Contrary to our hypotheses, we find limited evidence of a curvilinear relationship between networking and innovative work behaviors, that is, too little or too much networking was not associated with reduced innovative work behaviors.
Clinicians’ Experience of Collaboration in the Treatment of Suicidal Clients Within the Collaborative Assessment and Management of Suicidality Framework
Authors: Fogarty Bríd , Houghton Sharon , Galavan Eoin , O’Súilleabháin Páraic S. 
Published: June 2021

Introduction There is little known about the clinicians’ experience of collaboration using the Collaborative Assessment and Management of Suicide (CAMS) framework. This study aimed to give voice to the clinician experience. Method A qualitative design utilised semi-structured interviews with ten psychologists who worked in a Suicide Assessment and Treatment Service (SATS) in Ireland which utilises the CAMS framework. Results An Interpretative Phenomenological Analysis (IPA) approach revealed several important findings. The superordinate themes included ‘Finding Safety’, ‘Regulation of the Self’, ‘Connecting’, and ‘Systemic Challenges’. Discussion The CAMS framework plays an important role in providing a safe base for the clinician (in terms of understanding suicidality, in addition to the structures of the framework). It provides a mechanism in which to process difficult emotions, and a way of communicating a formulation of suicide to the treating team. Importantly, the CAMS emerged as facilitating a collaborative, therapeutic way of working.
Role of digital tomosynthesis in the context of tuberculosis contact investigation: comparisons with digital radiography
Authors: Mok Jeongha , Yeom Jeong A , Nam Su Won , Yoo Jun Mi , Lee Ji Won , Lee Geewon , Kim Kun-Il , Jeong Yeon Joo 
Published: June 2021

Background Chest radiography value as a screening tool in those exposed to pulmonary tuberculosis (TB) is reduced by its lower sensitivity to detect small intrapulmonary lesions. Purpose To evaluate the efficacy of digital tomosynthesis (DTS) screening of individuals that had contacted persons with active TB using low-dose computed tomography (CT) as the reference standard methods. Material and Methods This retrospective, community-based screening study of 90 adults who had been in close contact with a TB case was undertaken at our institution. All individuals underwent clinical evaluation, digital radiography (DR), DTS, and low-dose chest CT. Observers assessed and classified DR and DTS images using CT as the reference-standard method. Based on clinical and imaging findings, TB status was classified as normal, latent, minimal, subclinical, and active. Diagnostic performances of DTS and DR for the interpretation of correct diagnosis were calculated. Results The estimated effective doses for DR, DTS, and low-dose CT were 0.01 mSv, 0.1 mSv, and 0.33 mSv, respectively. TB statuses of the 90 individuals were as follows: 62 latent (68.9%); two subclinical (2.2%); and one minimal (1.1%). The sensitivities, specificities, and accuracies of DTS and DR in the interpretation of correct diagnosis were 75.8%, 100%, 91.1% and 48.5%, 96.5%, 78.9%, respectively. Conclusion DTS appears to be superior to DR for the detection of lung lesions in individuals with TB contacts. DTS can offer a reasonable option for TB contact investigation.
Mutations in domain V of Mycoplasma pneumoniae 23S rRNA and clinical characteristics of pediatric M. pneumoniae pneumonia in Nanjing, China
Authors: Xu Changdi , Deng Huan , Zhang Jiamin , Zhu Yifan , Rong Qiangquan , Quan Yao , Tang Heng , Zhao Deyu 
Published: June 2021

Objective To investigate the prevalence of mutations in domain V of Mycoplasma pneumoniae (MP) 23S ribosomal RNA (rRNA) and the clinical characteristics of pediatric MP pneumonia (MPP) in Nanjing, China. Methods Domain V of 23S rRNA was sequenced in MP strains collected from children diagnosed with MPP in Nanjing. Clinical and laboratory data were obtained. Results Among the 276 MP strains, 255 (92.39%) harbored mutations, primarily A2063G in domain V of MP 23S rRNA. When children were stratified according to the presence or absence of mutations, no significant differences were found in sex, age, the MP DNA load at enrollment, lymphocyte counts, pulmonary complications, immunomodulator levels, fever duration, the duration of fever after macrolide therapy, and hospital stay. The prevalence of refractory MPP in the two groups was similar. Children with refractory MPP exhibited higher MP DNA loads than those with non-refractory MPP. Conclusions Despite the high prevalence of the A2063G mutation in domain V of MP 23S rRNA, mutations were not associated with the clinical characteristics of MPP. The MP DNA load significantly differed between refractory and non-refractory MPP.
Arthroscopic Treatment and Outcomes of Borderline Dysplasia With Acetabular Retroversion: A Matched-Control Study From the MASH Study Group
Authors: Matsuda Dean , Kivlan Benjamin R. , Nho Shane J. , Wolff Andrew B. , Salvo John P. , Christoforetti John J. , Martin RobRoy L. , Carreira Dominic S. 
Published: June 2021

Background: Although acetabular retroversion (AR) occurs in dysplasia, management of the crossover sign (COS) or outcomes in borderline dysplasia (BD) with AR have not been reported. Purpose: To report any differences in the management of the COS in BD and nondysplastic hips and to report comparative outcomes of BD with AR with matched controls with BD or AR (ie, focal pincer femoroacetabular impingement [FAI]). Study design: Cohort study; Level of evidence, 3. Methods: A multicenter matched-pair study was performed with data from a large prospectively collected database. Inclusion criteria were patients who had undergone primary unilateral hip arthroscopy including labral repair for FAI and/or chondral pathology without significant osteoarthritis (ie, Tönnis grade 0 or 1). The study group (BD+AR) was defined radiographically by lateral center-edge angle (LCEA) on standing anteroposterior pelvis of 18° to 25° and positive COS. A 1:1:1 matching on age, sex, and body mass index was performed with a control group with BD and another control group with AR (LCEA, >25°+COS). Acetabuloplasty rates were determined for each group. Mean 2-year outcomes including the 12-Item International Hip Outcome Tool (iHOT-12), minimally clinical important difference (MCID), substantial clinical benefit (SCB), and Patient Acceptable Symptom State (PASS) scores were compared. Subanalysis of the study group both with and without acetabuloplasty was performed. Results: There were 69 patients, with 23 in the study group and 23 in each control group. The effect of dysplasia with or without the presence of the COS resulted in changes in acetabuloplasty rates, with 0% performed in the BD group, 35% in the BD+AR study group, and 91% in the AR group ( P = .001). Arthroscopic outcomes demonstrated similar and significant mean 2-year improvement of iHOT-12 patient-reported outcomes, MCID, SCB, and PASS scores in the study and both control groups. There was a trend within the study group toward greater postoperative iHOT-12 scores in patients who received anterior-based acetabuloplasty than those who did not receive acetabuloplasty (81.7 and 70.4, respectively; P = .11). Conclusion: Acetabular coverage influences the management of the COS, with significantly lower acetabuloplasty rates in BD with AR compared with AR without BD (focal pincer impingement). Symptomatic patients with combined BD and AR had similar significant successful outcomes to those of patients with BD and those with AR (focal pincer impingement), whether treated without acetabuloplasty or, less frequently, with limited anterior-based acetabuloplasty.
Characterizing Underlying Cognitive Components of ADHD Presentations and Co-morbid Diagnoses: A Diffusion Decision Model Analysis
Authors: Ging-Jehli Nadja R. , Arnold L. Eugene , Roley-Roberts Michelle E. , deBeus Roger 
Published: June 2021

Objective: To Explore whether subtypes and comorbidities of attention-deficit hyperactivity disorder (ADHD) induce distinct biases in cognitive components involved in information processing. Method: Performance on the Integrated Visual and Auditory Continuous Performance Test (IVA-CPT) was compared between 150 children (aged 7 to 10) with ADHD, grouped by DSM-5 presentation (ADHD-C, ADHD-I) or co-morbid diagnoses (anxiety, oppositional defiant disorder [ODD], both, neither), and 60 children without ADHD. Diffusion decision modeling decomposed performance into cognitive components. Results: Children with ADHD had poorer information integration than controls. Children with ADHD-C were more sensitive to changes in presentation modality (auditory/visual) than those with ADHD-I and controls. Above and beyond these results, children with ADHD+anxiety+ODD had larger increases in response biases when targets became frequent than children with ADHD-only or with ADHD and one comorbidity. Conclusion: ADHD presentations and comorbidities have distinct cognitive characteristics quantifiable using DDM and IVA-CPT. We discuss implications for tailored cognitive-behavioral therapy.