bluuebunny/crossref_metadata_2025_split huggingface dataset:
Locally Derived, Meteoric Fluid Infiltration Was Responsible for Widespread Late Paleozoic Illite Authigenesis in the Appalachian Basin
Authors: Boles A. , van der Pluijm B. 
Published: June 2020

AbstractIsotopic and geochronologic investigation of authigenic, K‐bearing clays in the Appalachian Plateau of the northeastern U.S. Midcontinent yields new insights about the tectonic and diagenetic history of the North American sedimentary cover sequence. In situ texture analysis by High Resolution X‐ray Texture Goniometry indicates preservation of bedding‐parallel diagenetic fabrics with burial depths of 2–5 km, and illite mineralization temperatures are spatially variable, ranging from 80 to 190 °C, correlating to similar depths of 3–6 km. The mineralizing geofluid is surface derived, with δD values ranging from −48‰ to −72‰ (in the range of predicted Pangea meteoric fluid). In addition, we find that mineralizing fluid δD values increase away from the orogenic front, consistent with a rain shadow effect from the high elevation Appalachian orogen. The age of authigenic illite is constrained by 40Ar/39Ar geochronology to 308–318 Ma, reflecting Upper Carboniferous diagenesis. We postulate that far‐field stress transmission from continent‐continent collision created regional permeability pathways for surface fluids, altering the hydrologic architecture of the brittle crust and allowing meteoric fluid infiltration into upper crustal rocks. This interpretation challenges the popular view of tectonically forced, lateral fluid flow from the Appalachian orogen (squeegee hypothesis).
Can Managed Aquifer Recharge Mitigate the Groundwater Overdraft in California's Central Valley?
Authors: Alam Sarfaraz , Gebremichael Mekonnen , Li Ruopu , Dozier Jeff , Lettenmaier Dennis P. 
Published: June 2020

AbstractGroundwater plays a critical role in sustaining agriculture in California's Central Valley (CV). However, groundwater storage in the CV has been declining by around 3 km3/year over the last several decades, with much larger declines during the 2007–2009 and 2012–2015 droughts. Managed Aquifer Recharge (MAR) can potentially mitigate existing overdraft by recharging excess streamflows (during flood periods) to the aquifers. However, the degree to which the existing CV groundwater overdraft might be mitigated by MAR is unknown. We applied a coupled surface water‐groundwater simulation model to quantify the potential for groundwater overdraft recovery via MAR. To quantify the potential benefit of MAR, we used the coupled surface water‐groundwater model to simulate water allocation scenarios where streamflow above the 90th or 80th percentiles was reallocated to aquifers, subject to constraints on the maximum depth of applied water (0.61 and 3.05 m). Our results show that MAR could recover 9–22% of the existing groundwater overdraft CV‐wide based on a 56‐year simulation (1960–2015). However, the impact of MAR varies strongly among regions. In the southern CV where groundwater depletion is most serious, the contribution of MAR to the overdraft recovery would be small, only 2.7–3.2% in the Tulare basin and 3.2–7.8% in the San Joaquin basin. However, transferring excess winter flow from the northern to the southern CV for MAR would increase the overdraft recovery to 30% in San Joaquin and 62% in Tulare. Our results also indicate that MAR has the potential to supplement summer low flows (52–73%, CV‐wide) and reduce flood peaks.
Expanding Attention-Deficit/Hyperactivity Disorder Service Provision in Urban Socioeconomically Disadvantaged Communities: A Pilot Study
Authors: Chacko Anil , Hopkins Karen , Acri Mary , Mendelsohn Alan , Dreyer Benard 
Published: June 2020

Objective: Access to evidence-based psychosocial interventions for the treatment of attention-deficit/hyperactivity disorder (ADHD) is a challenge in urban, socioeconomically disadvantaged communities. Approaches that leverage existing but underdeveloped workforces and connects these with well-established settings that treat ADHD offers an opportunity to address this barrier. This pilot study focused on a preliminary test of the potential utility of paraprofessional-delivered behavioral parent training (BPT) to parents of children with ADHD being treated in a developmental behavioral pediatric practice. Method: In an open clinical trial of 7 families, Family Peer Advocate paraprofessionals delivered BPT to parents of children with ADHD. Parent reports of their child’s ADHD symptoms/oppositional defiant behaviors and functional impairment were assessed before, weekly during BPT, and immediately after BPT. Parents report of their positive and negative parenting behaviors were assessed before and immediately after BPT. Results: Findings demonstrated that participation in BPT was associated with improvements in child- and parent-level outcomes, with moderate to large effects across outcomes. Conclusions: Integrating existing service systems with oversight through pediatric psychologists offers opportunities to efficiently utilize resources, thereby increasing access to evidence-based interventions for ADHD in urban, socioeconomically disadvantaged communities. Implications for Impact Statement This study advances the scope of paraprofessional involvement in formal pediatric settings. In addition, it highlights the potential effectiveness of peer-to-peer delivered services.
Adapting PCIT to Address Mental Health Care Disparities Among Underserved Families Impacted by Pediatric Illness: A Case Series of Bedside PCIT
Authors: Christian-Brandt Allison S. , Santacrose Diana 
Published: June 2020

Objective: Medically ill children are at elevated risk for mental health issues ( Blackman, Gurka, Gurka, & Oliver, 2011 ), which can negatively affect health status ( DeMore, Adams, Wilson, & Hogan, 2005 ; Johnston & Martin-Herz, 2010 ). Given that children from diverse racial/ethnic backgrounds are disproportionately impacted by medical conditions ( Mehta, Lee, & Ylitalo, 2013 ) and experience marked mental health care disparities ( Marrast, Himmelstein, & Woolhandler, 2016 ), innovative interventions are necessary for meeting the needs of underserved families. Methods: The current study presents an adaptation of parent-child interaction therapy (PCIT) for medical settings that seeks to reduce barriers to care among underserved children with medical conditions and their families. We present outcomes from a case series of bedside PCIT among 5 low–socioeconomic status, medically ill children (3–6 years old; 2 Hispanic, 1 Black, 2 non-Hispanic White) exhibiting medical trauma and disruptive behavior. Main adaptations to standard PCIT included flexible setting delivery, psychoeducation on parenting a medically ill child, and modification of time-out based on child capacity. Results: All families completed treatment and demonstrated reliable and clinically meaningful change in child traumatic stress, child disruptive behavior, and parenting stress. Systematic behavioral observations also indicated improved parenting practices. Conclusions: Results suggest that PCIT can be adapted for medical settings and has the potential to address care disparities among diverse, low–socioeconomic status families impacted by pediatric medical illness. Continued research on bedside PCIT will further elucidate the feasibility and effectiveness of this adaptation, as compared with standard PCIT and typical behavioral health supports in medical settings. Implications for Impact Statement The present case series of an adaptation of parent-child interaction therapy for medically ill children yieled positive child and family outcomes among five low–socioeconomic status families across a variety of medical settings. Results highlight how bedside parent-child interaction therapy could help increase access and continuity of care among underserved pediatric populations while also filling a gap in the literature regarding behavioral parent training tailored for families impacted by pediatric illness.
The Teen Symposium: Engaging Adolescents and Young Adults With Sickle Cell Disease in Clinical Care and Research
Authors: Crosby Lori E. , Strong Heather , Johnson Alisha , Mitchell Monica J. 
Published: June 2020

Objective: In the United States, sickle cell disease (SCD) is the most prevalent genetic disorder affecting African American and Hispanic youth. Disparities in care have been reported for this population with adolescents and young adults (AYA) with SCD at increased risk for poor health outcomes. It is essential that AYA with SCD receive high-quality care and have access to disease-modifying therapies, yet engaging them in their care and clinical research studies to discover new treatments remains a challenge. Method: Our team developed an innovative approach to engage AYA with SCD in clinical care and research: the SCD Teen Symposium, which uses motivational interviewing strategies to educate AYA with SCD, their family members, and friends while providing concurrent opportunities for research participation. Results: Over a 6-year period, 81 AYA with SCD (47% male; M age = 14.58, SD = 2.9) and 162 family and friends (48% male; M age = 13.37, SD = 2.1) participated. Participants rated the symposium as acceptable ( M rating = 1.74, SD = 0.85) on a scale from 1 ( excellent) to 5 ( poor), and 72% reported they would recommend it to others. Research was rated as very important ( M rating = 1.21, SD = 0.46) by 81% of attendees on a scale from 1 ( very important) to 4 ( not important), and 82% reported increased trust in research. AYA suggested improvements including separate programming for younger and older teens. Conclusions: Results support the feasibility of the Teen Symposium as a model for increasing trust and potentially increasing participation in research. Future studies will determine whether it can be disseminated by other SCD clinics. Implications for Impact Statement This study describes a 1-day research and education event for adolescents and young adults with sickle cell disease, the Teen Symposium. After attending the symposium, teens reported more trust in research and that they would participate in research studies in the future.
Parent Decision-Making About Support for Siblings of Children With Cancer: Sociodemographic Influences
Authors: Oberoi Anjali R. , Cardona Nicole D. , Davis Kathryn A. , Pariseau Emily M. , Berk Deborah , Muriel Anna C. , Long Kristin A. 
Published: June 2020

Background: Siblings of children with cancer have elevated psychosocial risk. Sociodemographic factors (e.g., non-White race, low income, and low caregiver education) are associated with increased risk. Little is known about how sociodemographic factors influence families’ decisions to participate in sibling support services. This convergent mixed-methods study characterizes how sociodemographic factors influence parent decision-making to engage siblings in support. Method: A purposive sample of parents of children with cancer ( N = 28) participated in semistructured interviews that queried their perceptions of sibling support, including preferences for ideal support and perceived barriers to accessing support. Qualitative findings were merged with quantitative data to stratify by sociodemographic categories (ethnicity, parent-reported financial hardship, parent education). Applied thematic analysis was used to distill findings. Results: Sociodemographic differences emerged across parents’ decision-making on whether to engage with sibling support services. Some cross-cutting barriers to accessing sibling support were described by all groups. However, differences across sociodemographic groups emerged for other barriers to care and for preferences for sibling support. Conclusions: These findings inform the design and implementation of sibling support programs. Providers can work with families to craft individualized sibling support plans that align with the family’s preferences and circumvent perceived barriers, which may improve acceptability and use of support programming and ultimately improve siblings’ psychosocial outcomes. Implications for Impact Statement This article offers an overview of sociodemographic variables (ethnicity, financial hardship, parent education) associated with parents’ decision to engage in support for siblings of children of cancer. An understanding of these factors can support clinicians in the design and implementation of programs that are acceptable and accessible for all families of children with cancer.
Bosutinib for pretreated patients with chronic phase chronic myeloid leukemia: primary results of the phase 4 BYOND study
Authors: Hochhaus Andreas , Gambacorti-Passerini Carlo , Abboud Camille , Gjertsen Bjørn Tore , Brümmendorf Tim H. , Smith B. Douglas , Ernst Thomas , Giraldo-Castellano Pilar , Olsson-Strömberg Ulla , Saussele Susanne , Bardy-Bouxin Nathalie , Viqueira Andrea , Leip Eric , Russell-Smith T. Alexander , Leone Jocelyn , Rosti Gianantonio , Watts Justin , Giles Francis J. ,   on behalf of the BYOND Study Investigators, Abruzzese E. , Akard L. P. , Bosi A. , Cervantes F. , Charbonnier A. , Di Raimondo F. , Etienne G. , Garcia Gutierrez V. , Guerci-Bresler A. P. , Hjorth-Hansen H , Karsenti J. M. , Kelly K. R. , Le Coutre P. , Martinez Chamorro C. , Oehler V. G. , Orti Pascual G. , Petzer A. , Pungolino E. , Rege-Cambrin G. , Rigal-Huguet F. , Roboz G. J. , Rousselot P. , Sanchez-Guijo F. M. , Sanz Santillana G. , Schafhausen P. , Scheid C. , Schmidt S. , Specchia G. , Steegmann J. L. , Stenke L. 
Published: June 2020

AbstractBosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of cumulative confirmed major cytogenetic response (MCyR) rate by 1 year was 75.8% in Ph+ CP CML patients after one or two prior TKIs and 62.2% after three prior TKIs. Cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) rates by 1 year were 80.6% and 70.5%, respectively, in Ph+ CP CML patients overall. No patient progressed to AP/BP on treatment. Across all patients, the most common treatment-emergent adverse events were diarrhea (87.7%), nausea (39.9%), and vomiting (32.5%). The majority of patients had confirmed MCyR by 1 year and MMR by 1 year, further supporting bosutinib use for Ph+ CP CML patients resistant/intolerant to prior TKIs.
Functional genomics identifies new synergistic therapies for retinoblastoma
Authors: Aubry Arthur , Pearson Joel D. , Huang Katherine , Livne-bar Izhar , Ahmad Mohammad , Jagadeesan Madhavan , Khetan Vikas , Ketela Troy , Brown Kevin R. , Yu Tao , Lu Suying , Wrana Jeffrey L. , Moffat Jason , Bremner Rod 
Published: June 2020

AbstractLocal intravitreal or intra-arterial chemotherapy has improved therapeutic success for the pediatric cancer retinoblastoma (RB), but toxicity remains a major caveat. RB initiates primarily withRB1loss or, rarely,MYCNamplification, but the critical downstream networks are incompletely understood. We set out to uncover perturbed molecular hubs, identify synergistic drug combinations to target these vulnerabilities, and expose and overcome drug resistance. We applied dynamic transcriptomic analysis to identify network hubs perturbed in RB versus normal fetal retina, and performed in vivo RNAi screens inRB1nullandRB1wt;MYCNamporthotopic xenografts to pinpoint essential hubs. We employed in vitro and in vivo studies to validate hits, define mechanism, develop new therapeutic modalities, and understand drug resistance. We identified BRCA1 and RAD51 as essential for RB cell survival. Their oncogenic activity was independent of BRCA1 functions in centrosome, heterochromatin, or ROS regulation, and instead linked to DNA repair. RAD51 depletion or inhibition with the small molecule inhibitor, B02, killed RB cells in a Chk1/Chk2/p53-dependent manner. B02 further synergized with clinically relevant topotecan (TPT) to engage this pathway, activating p53–BAX mediated killing of RB but not human retinal progenitor cells. Paradoxically, a B02/TPT-resistant tumor exhibited more DNA damage than sensitive RB cells. Resistance reflected dominance of the p53–p21 axis, which mediated cell cycle arrest instead of death. Deleting p21 or applying the BCL2/BCL2L1 inhibitor Navitoclax re-engaged the p53–BAX axis, and synergized with B02, TPT or both to override resistance. These data expose new synergistic therapies to trigger p53-induced killing in diverse RB subtypes.
YES1 amplification confers trastuzumab–emtansine (T-DM1) resistance in HER2-positive cancer
Authors: Wang Lei , Wang Quanren , Xu Piaopiao , Fu Li , Li Yun , Fu Haoyu , Quan Haitian , Lou Liguang 
Published: June 2020

AbstractBackgroundTrastuzumab–emtansine (T-DM1), one of the most potent HER2-targeted drugs, shows impressive efficacy in patients with HER2-positive breast cancers. However, resistance inevitably occurs and becomes a critical clinical problem.MethodsWe modelled the development of acquired resistance by exposing HER2-positive cells to escalating concentrations of T-DM1. Signalling pathways activation was detected by western blotting, gene expression was analysed by qRT-PCR and gene copy numbers were determined by qPCR. The role of Yes on resistance was confirmed by siRNA-mediated knockdown and stable transfection-mediated overexpression. The in vivo effects were tested in xenograft model.ResultsWe found that Yes is overexpressed in T-DM1–resistant cells owing to amplification of chromosome region 18p11.32, where theYES1gene resides. Yes activated multiple proliferation-related signalling pathways, including EGFR, PI3K and MAPK, and led to cross-resistance to all types of HER2-targeted drugs, including antibody-drug conjugate, antibody and small molecule inhibitor. The outcome of this cross-resistance may be a clinically incurable condition. Importantly, we found that inhibiting Yes with dasatinib sensitised resistant cells in vitro and in vivo.ConclusionsOur study revealed thatYES1amplification conferred resistance to HER2-targeted drugs and suggested the potential application of the strategy of combining HER2 and Yes inhibition in the clinic.
SIX1 cooperates with RUNX1 and SMAD4 in cell fate commitment of Müllerian duct epithelium
Authors: Terakawa Jumpei , Serna Vanida A. , Nair Devi M. , Sato Shigeru , Kawakami Kiyoshi , Radovick Sally , Maire Pascal , Kurita Takeshi 
Published: June 2020

AbstractDuring female mammal reproductive tract development, epithelial cells of the lower Müllerian duct are committed to become stratified squamous epithelium of the vagina and ectocervix, when the expression of ΔNp63 transcription factor is induced by mesenchymal cells. The absence of ΔNp63 expression leads to adenosis, the putative precursor of vaginal adenocarcinoma. Our previous studies with genetically engineered mouse models have established that fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK), bone morphogenetic protein (BMP)/SMAD, and activin A/runt-related transcription factor 1 (RUNX1) signaling pathways are independently required for ΔNp63 expression in Müllerian duct epithelium (MDE). Here, we report that sine oculis homeobox homolog 1 (SIX1) plays a critical role in the activation of ΔNp63 locus in MDE as a downstream transcription factor of mesenchymal signals. In the developing mouse reproductive tract, SIX1 expression was restricted to MDE within the future cervix and vagina. SIX1 expression was totally absent in SMAD4 null MDE and was reduced in RUNX1 null and FGFR2 null MDE, indicating that SIX1 is under the control of vaginal mesenchymal factors: BMP4, activin A and FGF7/10. Furthermore, Six1, Runx1, and Smad4 gene-dose-dependently activated ΔNp63 expression in MDE within the vaginal fornix. Using a mouse model of diethylstilbestrol (DES)-associated vaginal adenosis, we found DES action through epithelial estrogen receptor α (ESR1) inhibits activation of ΔNp63 locus in MDE by transcriptionally repressing SIX1 and RUNX1 in the vaginal fornix.
Formation of ammonia–helium compounds at high pressure
Authors: Shi Jingming , Cui Wenwen , Hao Jian , Xu Meiling , Wang Xianlong , Li Yinwei 
Published: June 2020

AbstractUranus and Neptune are generally assumed to have helium only in their gaseous atmospheres. Here, we report the possibility of helium being fixed in the upper mantles of these planets in the form of NH3–He compounds. Structure predictions reveal two energetically stable NH3–He compounds with stoichiometries (NH3)2He and NH3He at high pressures. At low temperatures, (NH3)2He is ionic with NH3 molecules partially dissociating into (NH2)− and (NH4)+ ions. Simulations show that (NH3)2He transforms into intermediate phase at 100 GPa and 1000 K with H atoms slightly vibrate around N atoms, and then to a superionic phase at ~2000 K with H and He exhibiting liquid behavior within the fixed N sublattice. Finally, (NH3)2He becomes a fluid phase at temperatures of 3000 K. The stability of (NH3)2He at high pressure and temperature could contribute to update models of the interiors of Uranus and Neptune.
The genome of Prasinoderma coloniale unveils the existence of a third phylum within green plants
Authors: Li Linzhou , Wang Sibo , Wang Hongli , Sahu Sunil Kumar , Marin Birger , Li Haoyuan , Xu Yan , Liang Hongping , Li Zhen , Cheng Shifeng , Reder Tanja , Çebi Zehra , Wittek Sebastian , Petersen Morten , Melkonian Barbara , Du Hongli , Yang Huanming , Wang Jian , Wong Gane Ka-Shu , Xu Xun , Liu Xin , Van de Peer Yves , Melkonian Michael , Liu Huan 
Published: June 2020

AbstractGenome analysis of the pico-eukaryotic marine green algaPrasinoderma colonialeCCMP 1413 unveils the existence of a novel phylum within green plants (Viridiplantae), the Prasinodermophyta, which diverged before the split of Chlorophyta and Streptophyta. Structural features of the genome and gene family comparisons revealed an intermediate position of theP. colonialegenome (25.3 Mb) between the extremely compact, small genomes of picoplanktonic Mamiellophyceae (Chlorophyta) and the larger, more complex genomes of early-diverging streptophyte algae. Reconstruction of the minimal core genome of Viridiplantae allowed identification of an ancestral toolkit of transcription factors and flagellar proteins. Adaptations ofP. colonialeto its deep-water, oligotrophic environment involved expansion of light-harvesting proteins, reduction of early light-induced proteins, evolution of a distinct type of C4photosynthesis and carbon-concentrating mechanism, synthesis of the metal-complexing metabolite picolinic acid, and vitamin B1, B7and B12auxotrophy. TheP. colonialegenome provides first insights into the dawn of green plant evolution.