bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clearance of therapy‐induced senescent tumor cells by the senolytic ABT‐263 via interference with BCL‐XL–BAX interaction
Authors: Saleh Tareq , Carpenter Valerie J. , Tyutyunyk‐Massey Liliya , Murray Graeme , Leverson Joel D. , Souers Andrew J. , Alotaibi Moureq R. , Faber Anthony C. , Reed Jason , Harada Hisashi , Gewirtz David A. 
Published: July 2020

Tumor cells undergo senescence in response to both conventional and targeted cancer therapies. The induction of senescence in response to cancer therapy can contribute to unfavorable patient outcomes, potentially including disease relapse. This possibiliy is supported by our findings that tumor cells induced into senescence by doxorubicin or etoposide can give rise to viable tumors in vivo. We further demonstrate sensitivity of these senescent tumor cells to the senolytic ABT‐263 (navitoclax), therefore providing a “two‐hit” approach to eliminate senescent tumor cells that persist after exposure to chemotherapy or radiation. The sequential combination of therapy‐induced senescence and ABT‐263 could shift the response to therapy toward apoptosis by interfering with the interaction between BCL‐XL and BAX. The administration of ABT‐263 after either etoposide or doxorubicin also resulted in marked, prolonged tumor suppression in tumor‐bearing animals. These findings support the premise that senolytic therapy following conventional cancer therapy may improve therapeutic outcomes and delay disease recurrence.
Epithelial/mesenchymal heterogeneity of high‐grade serous ovarian carcinoma samples correlates with miRNA let‐7 levels and predicts tumor growth and metastasis
Authors: Chirshev Evgeny , Hojo Nozomi , Bertucci Antonella , Sanderman Linda , Nguyen Anthony , Wang Hanmin , Suzuki Tise , Brito Emmanuel , Martinez Shannalee R. , Castañón Christine , Mirshahidi Saied , Vazquez Marcelo E. , Wat Pamela , Oberg Kerby C. , Ioffe Yevgeniya J. , Unternaehrer Juli J. 
Published: July 2020

Patient‐derived samples present an advantage over current cell line models of high‐grade serous ovarian cancer (HGSOC) that are not always reliable and phenotypically faithful models of in vivo HGSOC. To improve upon cell line models of HGSOC, we set out to characterize a panel of patient‐derived cells and determine their epithelial and mesenchymal characteristics. We analyzed RNA and protein expression levels in patient‐derived xenograft (PDX) models of HGSOC, and functionally characterized these models using flow cytometry, wound healing assays, invasion assays, and spheroid cultures. Besides in vitro work, we also evaluated the growth characteristics of PDX in vivo (orthotopic PDX). We found that all samples had hybrid characteristics, covering a spectrum from an epithelial‐to‐mesenchymal state. Samples with a stronger epithelial phenotype were more active in self‐renewal assays and more tumorigenic in orthotopic xenograft models as compared to samples with a stronger mesenchymal phenotype, which were more migratory and invasive. Additionally, we observed an inverse association between microRNA let‐7 (lethal‐7) expression and stemness, consistent with the loss of let‐7 being an important component of the cancer stem cell phenotype. We observed that lower let‐7 levels were associated with the epithelial state and a lower epithelial mesenchymal transition (EMT) score, more efficient spheroid and tumor formation, and increased sensitivity to platinum‐based chemotherapy. Surprisingly, in these HGSOC cells, stemness could be dissociated from invasiveness: Cells with lower let‐7 levels were more tumorigenic, but less migratory, and with a lower EMT score, than those with higher let‐7 levels. We conclude that let‐7 expression and epithelial/mesenchymal state are valuable predictors of HGSOC proliferation, in vitro self‐renewal, and tumor burden in vivo.
Development and execution of a pandemic preparedness plan: Therapeutic medical physics and radiation dosimetry during the COVID‐19 crisis
Authors: Riegel Adam C. , Chou Henry , Baker Jameson , Antone Jeffrey , Potters Louis , Cao Yijian 
Published: July 2020

AbstractThe SARS‐CoV‐2 coronavirus pandemic has spread around the world including the United States. New York State has been hardest hit by the virus with over 380 000 citizens with confirmed COVID‐19, the illness associated with the SARS‐CoV‐2 virus. At our institution, the medical physics and dosimetry group developed a pandemic preparedness plan to ensure continued operation of our service. Actions taken included launching remote access to clinical systems for all dosimetrists and physicists, establishing lines of communication among staff members, and altering coverage schedules to limit on‐site presence and decrease risk of infection. The preparedness plan was activated March 23, 2020, and data were collected on treatment planning and chart checking efficiency for 6 weeks. External beam patient load decreased by 25% during the COVID‐19 crisis, and special procedures were almost entirely eliminated excepting urgent stereotactic radiosurgery or brachytherapy. Efficiency of treatment planning and chart checking was slightly better than a comparable 6‐week interval in 2019. This is most likely due to decreased patient load: Fewer plans to generate and more physicists available for checking without special procedure coverage. Physicists and dosimetrists completed a survey about their experience during the crisis and responded positively about the preparedness plan and their altered work arrangements, though technical problems and connectivity issues made the transition to remote work difficult. Overall, the medical physics and dosimetry group successfully maintained high‐quality, efficient care while minimizing risk to the staff by minimizing on‐site presence. Currently, the number of COVID‐19 cases in our area is decreasing, but the preparedness plan has demonstrated efficacy, and we will be ready to activate the plan should COVID‐19 return or an unknown virus manifest in the future.
Health Disparities Research with American Indian Communities: The Importance of Trust and Transparency
Authors: Skewes Monica C. , Gonzalez Vivian M. , Gameon Julie A. , FireMoon Paula , Salois Emily , Rasmus Stacy M. , Lewis Jordan P. , Gardner Scott A. , Ricker Adriann , Reum Martel 
Published: July 2020

AbstractAmerican Indian and Alaska Native (AI/AN) communities experience notable health disparities associated with substance use, including disproportionate rates of accidents/injuries, diabetes, liver disease, suicide, and substance use disorders. Effective treatments for substance use are needed to improve health equity for AI/AN communities. However, an unfortunate history of unethical and stigmatizing research has engendered distrust and reluctance to participate in research among many Native communities. In recent years, researchers have made progress toward engaging in ethical health disparities research by using a community‐based participatory research (CBPR) framework to work in close partnership with community members throughout the research process. In this methodological process paper, we discuss the collaborative development of a quantitative survey aimed at understanding risk and protective factors for substance use among a sample of tribal members residing on a rural AI reservation with numerous systems‐level barriers to recovery and limited access to treatment. By using a CBPR approach and prioritizing trust and transparency with community partners and participants, we were able to successfully recruit our target sample and collect quality data from nearly 200 tribal members who self‐identified as having a substance use problem. Strategies for enhancing buy‐in and recruiting a community sample are discussed.
Growth in individuals with Saul–Wilson syndrome
Authors: Ferreira Carlos R. , Niiler Timothy , Duker Angela L. , Jackson Andrew P. , Bober Michael B. 
Published: July 2020

AbstractSaul–Wilson syndrome (SWS) is a rare autosomal recessive disorder characterized by microcephalic primordial dwarfism, spondyloepimetaphyseal dysplasia, characteristic facial findings, clubfoot, brachydactyly, bilateral cataracts, and hearing loss. Recently, recurrent mutations in COG4, encoding a component of the Conserved Oligomeric Golgi (COG) complex, were identified. We created detailed growth curves for stature, weight, and head circumference, as well as weight‐for‐length and weight velocity charts for younger children, derived from hundreds of data points obtained by retrospective chart review from 14 individuals with molecularly‐confirmed SWS. In addition, we performed statistical comparisons of height‐for‐age model fits before and after initiation of growth hormone supplementation, and found that this therapy does not appear to influence height in individuals with SWS. We hope that these charts will represent valuable tools for clinicians, both in assessing whether SWS seems an appropriate diagnosis, as well as to monitor growth of affected individuals. In particular, we hope that our detailed growth characterization will reduce morbidity resulting from unnecessarily aggressive nutritional interventions by well‐intentioned physicians trying to promote weight gain, an unrealistic goal in this genetically‐determined cause of primordial dwarfism.
Genome‐wide admixture mapping ofDSM‐IValcohol dependence, criterion count, and the self‐rating of the effects of ethanol in African American populations
Authors: Lai Dongbing , Kapoor Manav , Wetherill Leah , Schwandt Melanie , Ramchandani Vijay A. , Goldman David , Chao Michael , Almasy Laura , Bucholz Kathleen , Hart Ronald P. , Kamarajan Chella , Meyers Jacquelyn L. , Nurnberger John I. , Tischfield Jay , Edenberg Howard J. , Schuckit Marc , Goate Alison , Scott Denise M. , Porjesz Bernice , Agrawal Arpana , Foroud Tatiana 
Published: July 2020

AbstractAfrican Americans (AA) have lower prevalence of alcohol dependence and higher subjective response to alcohol than European Americans. Genome‐wide association studies (GWAS) have identified genes/variants associated with alcohol dependence specifically in AA; however, the sample sizes are still not large enough to detect variants with small effects. Admixture mapping is an alternative way to identify alcohol dependence genes/variants that may be unique to AA. In this study, we performed the first admixture mapping of DSM‐IV alcohol dependence diagnosis, DSM‐IV alcohol dependence criterion count, and two scores from the self‐rating of effects of ethanol (SRE) as measures of response to alcohol: the first five times of using alcohol (SRE‐5) and average of SRE across three times (SRE‐T). Findings revealed a region on chromosome 4 that was genome‐wide significant for SRE‐5 (pvalue = 4.18E‐05). Fine mapping did not identify a single causal variant to be associated with SRE‐5; instead, conditional analysis concluded that multiple variants collectively explained the admixture mapping signal.PPARGC1A, a gene that has been linked to alcohol consumption in previous studies, is located in this region. Our finding suggests that admixture mapping is a useful tool to identify genes/variants that may have been missed by current GWAS approaches in admixed populations.
Huntingtin geneCAGrepeat size affects autism risk: Family‐based and case–control association study
Authors: Piras Ignazio Stefano , Picinelli Chiara , Iennaco Raffaele , Baccarin Marco , Castronovo Paola , Tomaiuolo Pasquale , Cucinotta Francesca , Ricciardello Arianna , Turriziani Laura , Nanetti Lorenzo , Mariotti Caterina , Gellera Cinzia , Lintas Carla , Sacco Roberto , Zuccato Chiara , Cattaneo Elena , Persico Antonio M. 
Published: July 2020

AbstractThe Huntingtin (HTT) gene contains a CAG repeat in exon 1, whose expansion beyond 39 repeats consistently leads to Huntington's disease (HD), whereas normal‐to‐intermediate alleles seemingly modulate brain structure, function and behavior. The role of the CAG repeat in Autism Spectrum Disorder (ASD) was investigated applying both family‐based and case–control association designs, with the SCA3 repeat as a negative control. Significant overtransmission of “long” CAG alleles (≥17 repeats) to autistic children and of “short” alleles (≤16 repeats) to their unaffected siblings (allp < 10−5) was observed in 612 ASD families (548 simplex and 64 multiplex). Surprisingly, both 193 population controls and 1,188 neurological non‐HD controls have significantly lower frequencies of “short” CAG alleles compared to 185 unaffected siblings and higher rates of “long” alleles compared to 548 ASD patients from the same families (p < .05–.001). The SCA3 CAG repeat displays no association. “Short” HTT alleles seemingly exert a protective effect from clinically overt autism in families carrying a genetic predisposition for ASD, while “long” alleles may enhance autism risk. Differential penetrance of autism‐inducing genetic/epigenetic variants may imply atypical developmental trajectories linked to HTT functions, including excitation/inhibition imbalance, cortical neurogenesis and apoptosis, neuronal migration, synapse formation, connectivity and homeostasis.
Language characterization in 16p11.2 deletion and duplication syndromes
Authors: Kim So Hyun , Green‐Snyder LeeAnne , Lord Catherine , Bishop Somer , Steinman Kyle J. , Bernier Raphael , Hanson Ellen , Goin‐Kochel Robin P. , Chung Wendy K. 
Published: July 2020

AbstractExpressive language impairment is one of the most frequently associated clinical features of 16p11.2 copy number variations (CNV). However, our understanding of the language profiles of individuals with 16p11.2 CNVs is still limited. This study builds upon previous work in the Simons Variation in Individuals Project (VIP, now known as Simons Searchlight), to characterize language abilities in 16p11.2 deletion and duplication carriers using comprehensive assessments. Participants included 110 clinically ascertained children and family members (i.e., siblings and cousins) with 16p11.2 BP4‐BP5 deletion and 58 with 16p11.2 BP4‐BP5 duplication between the ages of 2–23 years, most of whom were verbal. Regression analyses were performed to quantify variation in language abilities in the presence of the 16p11.2 deletion and duplication, both with and without autism spectrum disorder (ASD) and cognitive deficit. Difficulties in pragmatic skills were equally prevalent in verbal individuals in both deletion and duplication groups. NVIQ had moderate quantifiable effects on language scores in syntax and semantics/pragmatics (a decrease of less than 1 SD) for both groups. Overall, language impairments persisted even after controlling for ASD diagnosis and cognitive deficit. Language impairment is one of the core clinical features of individuals with 16p11.2 CNVs even in the absence of ASD and cognitive deficit. Results highlight the need for more comprehensive and rigorous assessment of language impairments to maximize outcomes in carriers of 16p11.2 CNVs.
Phylogenetic relationships in the genusCheracebus(Callicebinae, Pitheciidae)
Authors: Carneiro Jeferson , Sampaio Iracilda , Lima Thaynara , Silva‐Júnior José de S. , Farias Izeni , Hrbek Tomas , Valsecchi João , Boubli Jean , Schneider Horacio 
Published: July 2020

AbstractCheracebusis a new genus of New World primate of the family Pitheciidae, subfamily Callicebinae. Until recently,Cheracebuswas classified as thetorquatusspecies group of the genusCallicebus. The genusCheracebushas six species:C. lucifer, C. lugens, C. regulus, C. medemi, C. torquatus, andC. purinus, which are all endemic to the Amazon biome. Before the present study, there had been no conclusive interpretation of the phylogenetic relationships among most of theCheracebusspecies. The present study tests the monophyly of the genus and investigates the relationships among the differentCheracebusspecies, based on DNA sequencing of 16 mitochondrial and nuclear markers. The phylogenetic analyses were based on Maximum Likelihood, Bayesian Inference, and multispecies coalescent approaches. The divergence times and genetic distances between theCheracebustaxa were also estimated. The analyses confirmed the monophyly of the genus and a well‐supported topology, with the following arrangement: ((C. torquatus, C. lugens), (C. lucifer(C. purinus, C. regulus))). A well‐differentiated clade was also identified within part of the geographic range ofC. lugens, which warrants further investigation to confirm its taxonomic status.
Shift work and incidence of dementia: A Danish Nurse Cohort study
Authors: Jørgensen Jeanette Therming , Hansen Johnni , Westendorp Rudi G. J. , Nabe‐Nielsen Kirsten , Stayner Leslie Thomas , Simonsen Mette Kildevæld , Andersen Zorana Jovanovic 
Published: July 2020

AbstractIntroductionA few studies suggest that working night and rotating shifts increase the risk of dementia. We examined the association between shift work and the incidence of dementia in a cohort of female Danish nurses.MethodsWe linked Danish Nurse Cohort participants, who reported work schedules (day, evening, night, rotating shifts) in 1993 and/or 1999 and their duration in 2009, to Danish registers to obtain information on dementia hospitalizations and prescription medication until November 2018.ResultsAmong 6048 nurses who reported work schedules in 1993 and 1999, nurses working night shifts ≥6 years had higher dementia incidence (hazard ratio: 2.43, 95% confidence interval: 1.39 to 4.23) than those working day shifts ≥6 years. Among 8059 nurses who reported shift work duration, nurses working night shifts ≥6 years had higher dementia incidence than those working night shifts <1 year (1.47, 1.06 to 2.06).DiscussionPersistent night shift work may increase the risk of dementia.
Dealkenylative Alkenylation: Formal σ‐Bond Metathesis of Olefins
Authors: Swain Manisha , Sadykhov Gusein , Wang Ruoxi , Kwon Ohyun 
Published: July 2020

AbstractThe dealkenylative alkenylation of alkene C(sp3)−C(sp2) bonds has been an unexplored area for C−C bond formation. Herein 64 examples of β‐alkylated styrene derivatives, synthesized through the reactions of readily accessible feedstock olefins with β‐nitrostyrenes by ozone/FeII‐mediated radical substitutions, are reported. These reactions proceed with good efficiencies and high stereoselectivities under mild reaction conditions and tolerate an array of functional groups. Also demonstrated is the applicability of the strategy through several synthetic transformations of the products, as well as the syntheses of the natural product iso‐moracin and the drug (E)‐metanicotine.
Synergie von elektrostatischen und π‐π‐Wechselwirkungen für die Verwirklichung von künstlichen photosynthetischen Modellsystemen auf Nano‐Ebene
Authors: Anaya‐Plaza Eduardo , Joseph Jan , Bauroth Stefan , Wagner Maximilian , Dolle Christian , Sekita Michael , Gröhn Franziska , Spiecker Erdmann , Clark Timothy , de la Escosura Andrés , Guldi Dirk M. , Torres Tomás 
Published: July 2020

AbstractIm Zuge der Entwicklung von effizienteren, lichtaktiven Elektronen‐Donor‐Akzeptor‐Systemen ist wenig darüber bekannt, wie einzelne Bausteine in einem supramolekularen, Nanometer großen Gerüst miteinander wechselwirken, besonders in wässrigen Umgebungen. In dieser Arbeit beschreiben wir ein wässriges Elektronen‐Donor‐Akzeptor‐System, dessen Struktur im Nanobereich eine herausragende Stabilität und Effizienz aufweist. Unser Fokus lag auf einem tetrakationischen Zink(II)phthalocyanin (ZnPc) mit Pyren‐Gruppen, das eine beispiellose Form der Aggregation aufgrund einer subtilen Kooperation von elektrostatischen und π‐π Wechselwirkungen aufweist. Unsere Untersuchungen zeigen ein monokristallines Wachstum in Lösung und einen lichtinduzierten, symmetriebrechenden intermolekularen Elektronen‐Transfer zwischen benachbarten ZnPcs. Nach Zugabe von einem negativ geladenen Fulleren (C60) als Elektronenakzeptor konnte neben einer verbesserten Stabilität auch die energieverschwendende Ladungsrekombination unterdrückt werden, die in Abwesenheit von C60 stattfand. Im Ganzen betrachtet bietet dieses photosynthetische Modellsystem einen hohen Grad an Vororganisation, welche die effiziente Ladungstrennung und den anschließenden Ladungstransport begünstigt.
Tuning Electrical‐ and Photo‐Conductivity by Cation Exchange within a Redox‐Active Tetrathiafulvalene‐Based Metal–Organic Framework
Authors: Zhou Yan , Yu Fei , Su Jian , Kurmoo Mohamedally , Zuo Jing‐Lin 
Published: July 2020

AbstractTo activate electronic and optical functions of the redox‐active metal–organic framework, (Me2NH2)[InIII(TTFTB)]⋅0.7 C2H5OH⋅DMF (Me2NH2@1, TTFTB=tetrathiafulvalene‐tetrabenzoate, DMF=N,N‐dimethylformamide), has been exchanged by tetrathiafulvalenium (TTF.+) and N,N′‐dimethyl‐4,4′‐bipyridinium (MV2+). These cations provide electron carriers and photosensitivity. The exchange retains the crystallinity allowing single‐crystal to single‐crystal post‐synthetic transformation to TTF@1 and MV@1. Both TTF.+ and MV2+ enhance the electrical conductivity by a factor of 102 and the visible light induced photocurrent by 4 and 28 times, respectively. EPR evidences synergetic effect involving charge transfer between the framework redox‐active TTFTB bridges and MV2+. The results demonstrate that functionalization of MOF by cation exchange without perturbing the crystallinity extends possibilities to achieve switchable materials.
Synergy of Electrostatic and π–π Interactions in the Realization of Nanoscale Artificial Photosynthetic Model Systems
Authors: Anaya‐Plaza Eduardo , Joseph Jan , Bauroth Stefan , Wagner Maximilian , Dolle Christian , Sekita Michael , Gröhn Franziska , Spiecker Erdmann , Clark Timothy , de la Escosura Andrés , Guldi Dirk M. , Torres Tomás 
Published: July 2020

AbstractIn the scientific race to build up photoactive electron donor‐acceptor systems with increasing efficiencies, little is known about the interplay of their building blocks when integrated into supramolecular nanoscale arrays, particularly in aqueous environments. Here, we describe an aqueous donor‐acceptor ensemble whose emergence as a nanoscale material renders it remarkably stable and efficient. We have focused on a tetracationic zinc phthalocyanine (ZnPc) featuring pyrenes, which shows an unprecedented mode of aggregation, driven by subtle cooperation between electrostatic and π–π interactions. Our studies demonstrate monocrystalline growth in solution and a symmetry‐breaking intermolecular charge transfer between adjacent ZnPcs upon photoexcitation. Immobilizing a negatively charged fullerene (C60) as electron acceptor onto the monocrystalline ZnPc assemblies was found to enhance the overall stability, and to suppress the energy‐wasting charge recombination found in the absence of C60. Overall, the resulting artificial photosynthetic model system exhibits a high degree of preorganization, which facilitates efficient charge separation and subsequent charge transport.