bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of antenatal dietary myo-inositol supplementation on the incidence of gestational diabetes mellitus and fetal outcome: protocol for a double-blind randomised controlled trial
Authors: Ibrahim Ibrahim , Abdullahi Hala , Fagier Yassin , Ortashi Osman , Terranegra Annalisa , Okunoye Gbemisola 
Published: January 2022

IntroductionGestational diabetes mellitus (GDM) affects 23.6% of Qatari women and is associated with maternal and perinatal morbidity and long-term risk of developing type 2 diabetes. A number of challenges exist with current interventions, including non-compliance with dietary advice, the reluctance of mothers to ingest metformin tablets or use insulin injections. These challenges highlight the importance of pursuing evidence-based prevention strategies. Myo-inositol is readily available as an US Food and Drug Administration-approved food supplement with emerging but limited evidence suggesting it may be beneficial in reducing the incidence of GDM. Further studies, such as this one, from different ethnic contexts and with differing risk factors, are urgently needed to assess myo-inositol effects on maternal and neonatal outcomes.Methods and analysisThis study is a prospective, randomised, double-blinded, placebo controlled clinical trial to either myo-inositol supplementation or placebo.We plan to enrol 640 pregnant women attending antenatal care at Sidra Medicine, Doha, Qatar, 320 in each arm. All participants will complete at least 12 weeks of supplementation prior to undertaking the Oral Glucose Tolerance Test at 24–28 weeks. The daily use of the trial supplementation will continue until the end of pregnancy. All outcome measures will be collected from the electronic medical records.Ethics and disseminationEthical approval for the study was obtained on 12 April 2021 from Sidra Medicine (IRB number 1538656). Results of the primary trial outcome and secondary endpoints will be submitted for publication in a peer-reviewed journal.Trial registration numberProspectively registered on 26 May 2021. Registration number ISRCTN16448440 (ISRCTN registry).
Exploring hepatitis C virus testing and treatment engagement over time in Melbourne, Australia: a study protocol for a longitudinal cohort study (EC-Experience Cohort study)
Authors: O’Keefe Daniel , Gunn J , Ryan Kathleen , Djordjevic Filip , Kerr Phoebe , Gold Judy , Elsum Imogen , Layton Chloe , Chan Kico , Dietze Paul , Higgs Peter , Doyle Joseph , Stoové Mark A , Hellard Margaret , Pedrana A E 
Published: January 2022

IntroductionThe advent of direct acting antiviral therapy for hepatitis C virus (HCV) means the elimination of HCV is possible but requires sustained effort to achieve. Between 2016 and 2019, 44% of those living with HCV were treated in Australia. However, treatment uptake has declined significantly. In Australia, people who inject drugs (PWID) are the population most at risk of HCV acquisition. Eliminating HCV in Australia will require nuanced understanding of the barriers to HCV treatment experienced by PWID and tailored interventions to address these barriers. The EC-Experience Cohort study aims to explore the barriers and enablers reported by PWID to engagement in HCV care.Methods and analysisThe EC-Experience Cohort study is a prospective cohort of PWID, established in Melbourne, Australia in 2018. Participants are assigned into three study groups: (1) those not currently engaged in HCV testing; (2) those diagnosed with HCV but not currently engaged in treatment and (3) those completed treatment. Participants complete a total of four interviews every 6 months across an 18-month study period. Predictors of experience of key outcome events along the HCV care cascade will be explored over time.Ethics and disseminationEthical approval for the EC-Experience Cohort study was obtained by the Alfred Hospital Ethics Committee in Melbourne, Australia (Project Number: HREC/16/Alfred/164). All eligible participants are assessed for capacity to consent and partake in a thorough informed consent process. Results from the EC-Experience Cohort study will be disseminated via national and international scientific and public health conferences and peer-reviewed journal publications. Data from the EC-Experience Cohort study will improve the current understanding of the barriers to HCV care for PWID and guide the tailoring of service provision for specific subgroups. Understanding the barriers and how to increase engagement in care of PWID is critical to achieve HCV elimination goals.
Quantification of the Selective Advantage of Driver Mutations Is Dependent on the Underlying Model and Stage of Tumor Evolution
Authors: Bozic Ivana 
Published: January 2022

Abstract
Measuring the selective fitness advantages provided by driver mutations has the potential to facilitate a precise quantitative understanding of cancer evolution. However, accurately measuring the selective advantage of driver mutations has remained a challenge in the field. Early studies reported small selective advantages of drivers, on the order of 1%, whereas newer studies report much larger selective advantages, as high as 1,200%. In this article, we argue that the calculated selective advantages of cancer drivers are dependent on the underlying mathematical model and stage of cancer evolution and that comparisons of numerical values of selective advantage without regard for the underlying model and stage can lead to spurious conclusions.
Antibody–Drug Conjugates: A New Addition to the Treatment Landscape of EGFR-Mutant Non–Small Cell Lung Cancer
Authors: Lim Sun Min , Kim Chang Gon , Cho Byoung Chul 
Published: January 2022

Abstract
The emergence of treatment resistance to targeted agents is currently inevitable and inherently heterogeneous in cancer, presenting significant challenges for improving survival outcomes in patients. This is not an exception for cancers harboring EGFR mutations, one of the most prevalently observed oncogenic alterations in non–small cell lung cancer (NSCLC) targeted clinically. Currently, numerous efforts have attempted to delay or overcome acquired resistance to EGFR–tyrosine kinase inhibitors (TKI), changing the treatment landscape of EGFR-mutant NSCLC. Haikala and colleagues have developed a unique strategy using patritumab deruxtecan, an antibody–drug conjugate targeting human epidermal growth factor receptor 3 (HER3) linked to exatecan derivatives, for treating EGFR-mutant NSCLC. By incorporating EGFR TKIs to upregulate surface HER3 expression, the antitumor efficacy of patritumab deruxtecan was augmented in various preclinical models. In parallel, Jänne and colleagues reported the clinical activity of patrimumab deruxtecan in patients with EGFR-mutant NSCLC with prior EGFR TKI treatment. These two studies provide the grounds for hopeful anticipation for a novel strategy that concurrently targets compensatory feedback loops in addition to oncogenic signaling pathways.
See related article by Haikala et al., p. 130
Abstract P057: Targeting Treg cells with GITR activation alleviates resistance to immunotherapy in murine glioblastomas
Authors: Amoozgar Zohreh , Kloepper Jonas , Ren Jun , Tay Rong En , Kazer Samuel W. , Kiner Evgeny , Krishnan Shanmugarajan , Posada Jessica M. , Ghosh Mitrajit , Mamessier Emilie , Wong Christina , Ferraro Gino B. , Batista Ana , Wang Nancy , Badeaux Mark , Roberge Sylvie , Xu Lei , Huang Peigen , Shalek Alex K. , Fukumura Dai , Kim Hye-Jung , Jain Rakesh K. 
Published: January 2022

Abstract
Glioblastoma (GBM) shows high level of resistance to currently available treatments including the standard of care and immunotherapy, representing the most fatal cancer type. Our study revealed that immune suppression by regulatory T cells (Treg) secondary to therapy with immune checkpoint blocker (anti-PD1) confers this resistance. In the GBM tumor microenvironment, Treg cells with increased suppressive phenotype were found of which frequency and anergic phenotype increase after ICB therapy, potentially contributing to the resistance. Targeting Treg has a dual-barreled effect on enhancing anti-tumor immunity: GBM is highly infiltrated with Treg while CD8 T cells are excluded. In view of Treg's intrinsic reactivity to self-antigens, mobilizing converted Treg as effector T cells can be an effective strategy to a tumor type that expresses a low level of neoantigens including GBM. Our study revealed that GITR (glucocorticoid induced TNFR family related protein) is a desirable therapeutic target based on its increased expression on GBM Tregs as compared to peripheral Tregs. Engagement of GITR with agonistic antibody led to conversion of Treg to Th1-like effector T cells, which is accompanied with downregulation of Helios and IL-10 expression that are associated with Treg suppressive function. Through combining anti-GITR with anti-PD1 therapy, tumor recognition by converted Treg and CD8 T cells could be enhanced via IFNg induced promotion of MHC class I and II expression by GBM cells, which also resulted in T cell memory formation in the long-term survivors. To obtain clinically relevant information, we established a standard of care regimen consisting of surgery, radiation, and chemotherapy for orthotopic mouse GBM. We found that the anti-GITR +anti-PD1 therapy tailored to the GBM specific TME synergizes with the standard of care, suggesting a translational potential in patients.
Citation Format: Zohreh Amoozgar, Jonas Kloepper, Jun Ren, Rong En Tay, Samuel W. Kazer, Evgeny Kiner, Shanmugarajan Krishnan, Jessica M. Posada, Mitrajit Ghosh, Emilie Mamessier, Christina Wong, Gino B. Ferraro, Ana Batista, Nancy Wang, Mark Badeaux, Sylvie Roberge, Lei Xu, Peigen Huang, Alex K. Shalek, Dai Fukumura, Hye-Jung Kim, Rakesh K. Jain. Targeting Treg cells with GITR activation alleviates resistance to immunotherapy in murine glioblastomas [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P057.
A new proactive feature selection model based on the enhanced optimization algorithms to detect DRDoS attacks
Authors: Nuiaa Riyadh Rahef , Manickam Selvakumar , Alsaeedi Ali Hakem , Alomari Esraa Saleh 
Published: January 2022

Cyberattacks have grown steadily over the last few years. The distributed reflection denial of service (DRDoS) attack has been rising, a new variant of distributed denial of service (DDoS) attack. DRDoS attacks are more difficult to mitigate due to the dynamics and the attack strategy of this type of attack. The number of features influences the performance of the intrusion detection system by investigating the behavior of traffic. Therefore, the feature selection model improves the accuracy of the detection mechanism also reduces the time of detection by reducing the number of features. The proposed model aims to detect DRDoS attacks based on the feature selection model, and this model is called a proactive feature selection model proactive feature selection (PFS). This model uses a nature-inspired optimization algorithm for the feature subset selection. Three machine learning algorithms, i.e., k-nearest neighbor (KNN), random forest (RF), and support vector machine (SVM), were evaluated as the potential classifier for evaluating the selected features. We have used the CICDDoS2019 dataset for evaluation purposes. The performance of each classifier is compared to previous models. The results indicate that the suggested model works better than the current approaches providing a higher detection rate (DR), a low false-positive rate (FPR), <span>and increased accuracy detection (DA).</span> The PFS model shows better accuracy to detect DRDoS attacks with 89.59%.
Un análisis de contenido de libros de texto para la alfabetización emancipadora de adultos en el contexto educativo poscolonial. El caso de la Amazonia brasileña en los años 1980
Authors: Silva Fabricio Valentim da , Éthier Marc-André , Demers Stéphanie 
Published: January 2022

Esta investigación se centra en el estudio de la noción de emancipación en libros didácticos de inspiración freireana que sirvieron a la alfabetización de adultos en el contexto de la educación postcolonial en el norte de Brasil, entre los años 1960 y 1980. Este estudio se apoya en la metodología del análisis de contenido de libros de texto y en la literatura sobre la Educación a la Ciudadanía, pues el objetivo central fue construir y evaluar la solidez de un modelo conceptual de alfabetización emancipadora a través de tres pasos metodológicos para analizar los contenidos en libros de texto que son favorables para el desarrollo de dicho tipo de alfabetización. Se constató que en la muestra estudiada los tipos del ciudadano orientado a la justicia o de ciudadano participativo forman parte de los criterios primordiales que ayudan a definir los contenidos de libros de texto favorables a una alfabetización emancipadora.
Review Review of the New World species of Microplitis Foerster (Hymenoptera, Braconidae, Microgastrinae) attacking Sphingidae (Lepidoptera, Bombycoidea)
Authors: Ghafouri Moghaddam Mostafa , Tomlinson Sloan , Jaffe Samuel , Arias-Penna Diana Carolina , Whitfield James B. , Janzen Daniel H. , Hallwachs Winifred , Latibari Minoo Heidari 
Published: January 2022

Abstract
Microplitis Foerster is a highly diverse and cosmopolitan genus within Microgastrinae (Hymenoptera, Ichneumonoidea, Braconidae). Microplitis ceratomiae Riley, a widely distributed North American species, exclusively attacks sphingid caterpillars. In this paper, M. ceratomiae is reported parasitizing a caterpillar of Sphinx poecila Stephens (Sphingidae) which was collected feeding on Spiraea alba Du Roi (Rosaceae), a species of white meadowsweet native to the wet soils of the Allegheny Mountains and other portions of eastern North America. Here, we report and describe this new host-parasitoid-food plant association in southern New Hampshire, and include a distribution map for the species. Biological, ecological and phylogenetic analyses, and an identification key for the nine known species of Microplitis that attack sphingids in the New World are provided.
On a Solution of the Closure Problem for Dry Convective Boundary Layer Turbulence and Beyond
Authors: Gryanik Vladimir M. , Hartmann Jörg 
Published: January 2022

Abstract
We consider the closure problem of representing the higher-order moments (HOMs) in terms of lower-order moments, a central feature in turbulence modeling based on the Reynolds-averaged Navier–Stokes (RANS) approach. Our focus is on models suited for the description of asymmetric, nonlocal, and semiorganized turbulence in the dry atmospheric convective boundary layer (CBL). We establish a multivariate probability density function (PDF) describing populations of plumes that are embedded in a sea of weaker randomly spaced eddies, and apply an assumed delta-PDF approximation. The main content of this approach consists of capturing the bulk properties of the PDF. We solve the closure problem analytically for all relevant HOMs involving velocity components and temperature and establish a hierarchy of new non-Gaussian turbulence closure models of different content and complexity ranging from analytical to semianalytical. All HOMs in the hierarchy have a universal and simple functional form. They refine the widely used Millionshchikov closure hypothesis and generalize the famous quadratic skewness–kurtosis relationship to higher order. We examine the performance of the new closures by comparison with measurement, LES, and DNS data and derive empirical constants for semianalytical models, which are best for practical applications. We show that the new models have a good skill in predicting the HOMs for atmospheric CBL. Our closures can be implemented in second-, third-, and fourth-order RANS turbulence closure models of bi-, tri-, and four-variate levels of complexity. Finally, several possible generalizations of our approach are discussed.
Propagation of Thermohaline Anomalies and Their Predictive Potential along the Atlantic Water Pathway
Authors: Langehaug H. R. , Ortega P. , Counillon F. , Matei D. , Maroon E. , Keenlyside N. , Mignot J. , Wang Y. , Swingedouw D. , Bethke I. , Yang S. , Danabasoglu G. , Bellucci A. , Ruggieri P. , Nicolì D. , Årthun M. 
Published: January 2022

Abstract
We assess to what extent seven state-of-the-art dynamical prediction systems can retrospectively predict winter sea surface temperature (SST) in the subpolar North Atlantic and the Nordic seas in the period 1970–2005. We focus on the region where warm water flows poleward (i.e., the Atlantic water pathway to the Arctic) and on interannual-to-decadal time scales. Observational studies demonstrate predictability several years in advance in this region, but we find that SST skill is low with significant skill only at a lead time of 1–2 years. To better understand why the prediction systems have predictive skill or lack thereof, we assess the skill of the systems to reproduce a spatiotemporal SST pattern based on observations. The physical mechanism underlying this pattern is a propagation of oceanic anomalies from low to high latitudes along the major currents, the North Atlantic Current and the Norwegian Atlantic Current. We find that the prediction systems have difficulties in reproducing this pattern. To identify whether the misrepresentation is due to incorrect model physics, we assess the respective uninitialized historical simulations. These simulations also tend to misrepresent the spatiotemporal SST pattern, indicating that the physical mechanism is not properly simulated. However, the representation of the pattern is slightly degraded in the predictions compared to historical runs, which could be a result of initialization shocks and forecast drift effects. Ways to enhance predictions could include improved initialization and better simulation of poleward circulation of anomalies. This might require model resolutions in which flow over complex bathymetry and the physics of mesoscale ocean eddies and their interactions with the atmosphere are resolved.

Significance Statement
In this study, we find that dynamical prediction systems and their respective climate models struggle to realistically represent ocean surface temperature variability in the eastern subpolar North Atlantic and Nordic seas on interannual-to-decadal time scales. In previous studies, ocean advection is proposed as a key mechanism in propagating temperature anomalies along the Atlantic water pathway toward the Arctic Ocean. Our analysis suggests that the predicted temperature anomalies are not properly circulated to the north; this is a result of model errors that seems to be exacerbated by the effect of initialization shocks and forecast drift. Better climate predictions in the study region will thus require improving the initialization step, as well as enhancing process representation in the climate models.
Modulation of East African Boreal Fall Rainfall: Combined Effects of the Madden–Julian Oscillation (MJO) and El Niño–Southern Oscillation (ENSO)
Authors: Vashisht Amandeep , Zaitchik Benjamin 
Published: January 2022

Abstract
Climate variabilities can have significant impacts on rainfall in East Africa, leading to disruption in natural and human systems and affecting the lives of tens of millions of people. Subseasonal and interannual variabilities are critical components of total rainfall variability in the region. The goal of this study is to examine the combined effects of the Madden–Julian oscillation (MJO), operating at a subseasonal time scale, and El Niño–Southern Oscillation (ENSO), operating at an interannual scale, on the modulation of East African boreal fall [October–December (OND)] rainfall, commonly called the short rains. Composite analysis shows that daily rainfall responses depend on MJO phase and its interaction with ENSO state. In particular, MJO modulation of rainfall is generally stronger under El Niño conditions relative to ENSO neutral and La Niña conditions, leading to increased potential for daily precipitation excesses during wet MJO phases under El Niño. There is evidence for both dynamic and thermodynamic mechanisms associated with these impacts, including an increase in westerly moisture transport and easterly advection of temperature and moist static energy. Seasonal analysis shows that the frequency and intensity of wet MJO phases during an El Niño contribute notably to the seasonal total precipitation anomaly. This suggests that the MJO can mediate El Niño’s impact on OND rainfall in East Africa.
Enhanced Predictability of Rapidly Intensifying Tropical Cyclones over the Western North Pacific Associated with Snow Depth Changes over the Tibetan Plateau
Authors: Cai Yuhao , Han Xiang , Zhao Haikun , Klotzbach Philip J. , Wu Liguang , Raga Graciela B. , Wang Chao 
Published: January 2022

Abstract
This study finds an enhanced relationship in recent years between January–March eastern Tibetan Plateau snow depth (TPSD) and the frequency of rapidly intensifying tropical cyclones (RITCs) over the western North Pacific (WNP) during the following peak TC season (July–November). The correlation between TPSD and RITCs is significant during 2000–14 but was insignificant during 1979–99. During 2000–14, when TPSD increases, there is an enhanced low-level anomalous anticyclone over the subtropical eastern North Pacific mainly due to the combined effect of advection and dynamics of the climatological prevailing westerly jet. Northeasterly wind anomalies are observed on the flank of the anticyclonic circulation anomaly, favoring anomalously cool sea surface temperature (SST). These anomalies lead to an anomalous pattern similar to the Pacific meridional mode (PMM), via a wind–evaporation feedback and cold advection. A Gill-type Rossby response to the PMM-like negative phase results in an anticyclonic circulation anomaly over the WNP, suppressing RITCs during 2000–14. A nearly opposite circulation anomaly occurred when TPSD was lower during 2000–14. There is a weak relationship between TPSD and RITCs, due to the lack of a link between TPSD and the PMM-like pattern from 1979 to 1999. Decadal changes in the relationship between TPSD and RITCs are mainly due to the meridional displacement of the prevailing westerly jet, which may be in response to decadal-to-multidecadal variability of SST anomalies. These changes then result in changes in the relationship between January–March TPSD and the PMM-like pattern.

Significance Statement
Forecasts of tropical cyclone rapid intensification, typically defined to be when a tropical cyclone intensifies by at least 30 knots (∼15 m s−1) in 24 h, remain extremely challenging. This study finds an enhanced relationship since the start of the twenty-first century between winter–spring Tibetan Plateau snow depth and western North Pacific rapidly intensifying tropical cyclones, while the relationship between snow depth and rapidly intensifying tropical cyclones was weak from 1979 to 1999. Decadal changes in the relationship between Tibetan Plateau snow depth and western North Pacific rapidly intensifying tropical cyclones is mainly due to the north–south displacement of the prevailing westerly jet, which may be in response to a transition in a midlatitude North Pacific climate mode. This study highlights the importance of the synergetic impact of the land, air, and sea on tropical cyclone climate and provides a potential predictor for seasonal-to-decadal prediction of rapidly intensifying tropical cyclones.