bluuebunny/crossref_metadata_2025_split huggingface dataset:
The majority of A-to-I RNA editing is not required for mammalian homeostasis
Authors: Chalk Alistair M. , Taylor Scott , Heraud-Farlow Jacki E. , Walkley Carl R. 
Published: December 2019

Abstract
Background
Adenosine-to-inosine (A-to-I) RNA editing, mediated by ADAR1 and ADAR2, occurs at tens of thousands to millions of sites across mammalian transcriptomes. A-to-I editing can change the protein coding potential of a transcript and alter RNA splicing, miRNA biology, RNA secondary structure and formation of other RNA species. In vivo, the editing-dependent protein recoding of GRIA2 is the essential function of ADAR2, while ADAR1 editing prevents innate immune sensing of endogenous RNAs by MDA5 in both human and mouse. However, a significant proportion of A-to-I editing sites can be edited by both ADAR1 and ADAR2, particularly within the brain where both are highly expressed. The physiological function(s) of these shared sites, including those evolutionarily conserved, is largely unknown.

Results
To generate completely A-to-I editing-deficient mammals, we crossed the viable rescued ADAR1-editing-deficient animals (Adar1E861A/E861AIfih1−/−) with rescued ADAR2-deficient (Adarb1−/−Gria2R/R) animals. Unexpectedly, the global absence of editing was well tolerated. Adar1E861A/E861AIfih1−/−Adarb1−/−Gria2R/R were recovered at Mendelian ratios and age normally. Detailed transcriptome analysis demonstrated that editing was absent in the brains of the compound mutants and that ADAR1 and ADAR2 have similar editing site preferences and patterns.

Conclusions
We conclude that ADAR1 and ADAR2 are non-redundant and do not compensate for each other’s essential functions in vivo. Physiologically essential A-to-I editing comprises a small subset of the editome, and the majority of editing is dispensable for mammalian homeostasis. Moreover, in vivo biologically essential protein recoding mediated by A-to-I editing is an exception in mammals.
Statistical methods for testing X chromosome variant associations: application to sex-specific characteristics of bipolar disorder
Authors: Jons William A. , Colby Colin L. , McElroy Susan L. , Frye Mark A. , Biernacka Joanna M. , Winham Stacey J. 
Published: December 2019

AbstractBackgroundBipolar disorder (BD) affects both sexes, but important sex differences exist with respect to its symptoms and comorbidities. For example, rapid cycling (RC) is more prevalent in females, and alcohol use disorder (AUD) is more prevalent in males. We hypothesize that X chromosome variants may be associated with sex-specific characteristics of BD. Few studies have explored the role of the X chromosome in BD, which is complicated by X chromosome inactivation (XCI). This process achieves “dosage compensation” for many X chromosome genes by silencing one of the two copies in females, and most statistical methods either ignore that XCI occurs or falsely assume that one copy is inactivated at all loci. We introduce new statistical methods that do not make these assumptions.MethodsWe investigated this hypothesis in 1001 BD patients from the Genetic Association Information Network (GAIN) and 957 BD patients from the Mayo Clinic Bipolar Disorder Biobank. We examined the association of over 14,000 X chromosome single nucleotide polymorphisms (SNPs) with sex-associated BD traits using two statistical approaches that account for whether a SNP may be undergoing or escaping XCI. In the “XCI-informed approach,” we fit a sex-adjusted logistic regression model assuming additive genetic effects where we coded the SNP either assuming one copy is expressed or two copies are expressed based on prior knowledge about which regions are inactivated. In the “XCI-robust approach,” we fit a logistic regression model with sex, SNP, and SNP-sex interaction effects that is flexible to whether the region is inactivated or escaping XCI.ResultsUsing the “XCI-informed approach,” which considers only the main effect of SNP and does not allow the SNP effect to differ by sex, no significant associations were identified for any of the phenotypes. Using the “XCI-robust approach,” intergenic SNP rs5932307 was associated with BD (P= 8.3 × 10−8), with a stronger effect in females (odds ratio in males (ORM) = 1.13, odds ratio in females for a change of two allele copies (ORW2) = 3.86).ConclusionX chromosome association studies should employ methods which account for its unique biology. Future work is needed to validate the identified associations with BD, to formally assess the performance of both approaches under different true genetic architectures, and to apply these approaches to study sex differences in other conditions.
Tau- but not Aß -pathology enhances NMDAR-dependent depotentiation in AD-mouse models
Authors: Faldini Enrico , Ahmed Tariq , Bueé Luc , Blum David , Balschun Detlef 
Published: December 2019

AbstractMany mouse models of Alzheimer’s disease (AD) exhibit impairments in hippocampal long-term-potentiation (LTP), seemingly corroborating the strong correlation between synaptic loss and cognitive decline reported in human studies. In other AD mouse models LTP is unaffected, but other defects in synaptic plasticity may still be present. We recently reported that THY-Tau22 transgenic mice, that overexpress human Tau protein carrying P301S and G272 V mutations and show normal LTP upon high-frequency-stimulation (HFS), develop severe changes in NMDAR mediated long-term-depression (LTD), the physiological counterpart of LTP. In the present study, we focused on putative effects of AD-related pathologies on depotentiation (DP), another form of synaptic plasticity. Using a novel protocol to induce DP in the CA1-region, we found in 11–15 months old male THY-Tau22 and APPPS1–21 transgenic mice that DP was not deteriorated by Aß pathology while significantly compromised by Tau pathology. Our findings advocate DP as a complementary form of synaptic plasticity that may help in elucidating synaptic pathomechanisms associated with different types of dementia.
First field application of temperature sensor modules for groundwater flow detection near borehole heat exchanger
Authors: Michalski Alexander , Klitzsch Norbert 
Published: December 2019

AbstractHere, we present the first application of a temperature sensor module (TSM) for deducing groundwater flow velocity and direction at borehole heat exchangers (BHEs). The TSM maps the horizontal temperature distribution around a BHE. As groundwater flow distorts this temperature distribution, flow velocity and direction can be inferred from the measured temperatures. As modular systems, TSMs can be attached to a BHE at any depth. For the studied BHE, the depths of interest are 82 m and at 94 m. We recorded TSM data for 2 weeks before and during the operation of the BHE. After simulating the working fluid temperature, we model the horizontal temperature distributions using the working fluid temperatures at the depths of interest as input. We use the latter simulations for inferring groundwater flow by minimizing the root mean square error between the measured and simulated temperatures. We obtain a groundwater flow of 0.4 m/day in the NW direction and groundwater flow below the detection limit of 0.01 m to 0.02 m/day at 82 m and 94 m depths, respectively. A flow meter measurement in a nearby groundwater well confirms the flow direction at 82 m but gives an order of magnitude higher velocity, which we attribute to the measurement principle. Moreover, long-term monitoring of a BHE equipped with multiple TSMs could provide information on seasonal variations in groundwater flow, changes in the thermal properties of the BHE filling or changes in the thermal resistance between BHE and ground.
Optimizing Chimeric Antigen Receptor T-Cell Therapy for Adults With Acute Lymphoblastic Leukemia
Authors: Frey Noelle V. , Shaw Pamela A. , Hexner Elizabeth O. , Pequignot Edward , Gill Saar , Luger Selina M. , Mangan James K. , Loren Alison W. , Perl Alexander E. , Maude Shannon L. , Grupp Stephan A. , Shah Nirav N. , Gilmore Joan , Lacey Simon F. , Melenhorst Jos J. , Levine Bruce L. , June Carl H. , Porter David L. 
Published: December 2019

PURPOSE The anti-CD19 chimeric antigen receptor T-cell therapy tisagenlecleucel (CTL019) has an 81% response rate in children with relapsed or chemotherapy refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). Cytokine release syndrome (CRS) is a life-threatening treatment-related toxicity that limits the full therapeutic potential in adults. We report outcomes for adults with r/r ALL treated with an optimized CTL019 dosing and CRS management strategy. METHODS Adults with r/r B-cell ALL received CTL019 in 1 of 2 trials. Patients received lymphodepletion followed by CTL019 as either a one-time infusion or fractionated infusions split over 3 days (day 1, 10%; day 2, 30%; day 3, 60%), which allowed for day 2 and day 3 doses to be held for early CRS. Total planned CTL019 dose varied with adaptive protocol modifications in response to efficacy and CRS toxicity. RESULTS Thirty-five adults with r/r ALL received CTL019 in 1 of 3 dosing cohorts. The low-dose cohort (n = 9) received single or fractionated dosing and had manageable toxicity with a 33% complete remission (CR) rate. In the high-dose single infusion cohort, 3 of 6 patients with refractory CRS concurrent with culture-positive sepsis died, and 3 achieved CR. The 20 patients in the high-dose fractionated (HDF) cohort had a 90% CR rate and manageable CRS. The HDF cohort had the highest survival, with a 2-year overall survival of 73% (95% CI, 46% to 88%) and event-free survival of 49.5% (95% CI, 21% to 73%). CONCLUSION Fractionated dosing of CTL019 with intrapatient dose modification optimizes safety without compromising efficacy in adults with r/r ALL.
Patient-Centered Standards for Medically Integrated Dispensing: ASCO/NCODA Standards
Authors: Dillmon Melissa S. , Kennedy Erin B. , Anderson Mary K. , Brodersen Michael , Cohen Howard , D′Amato Steven L. , Davis Patty , Doshi Gury , Genschaw Stuart , Makhoul Issam , Ormsby Wayne , Panikkar Rajiv , Peng Eileen , Raez Luis E. , Ronnen Ellen A. , Wimbiscus Bill , Reff Michael 
Published: December 2019

PURPOSE To provide standards for medically integrated dispensing of oral anticancer drugs and supportive care medications. METHODS An Expert Panel was formed, and a systematic review of the literature on patient-centered best practices for the delivery of oral anticancer and supportive care drugs was performed to April 2019 using PubMed and Google Scholar. Available patient-centered standards, including one previously developed by the National Community Oncology Dispensing Association (NCODA), were considered for endorsement. Public comments were solicited and considered in preparation of the final manuscript. RESULTS A high-quality systematic review that was current to May 2016 was adopted into the evidence base. Five additional primary studies of multifaceted interventions met the inclusion criteria. These studies generally included a multicomponent intervention, often led by an oncology pharmacist, and also included patient education and regular follow-up and monitoring. These interventions resulted in significant improvements to patient quality and safety and demonstrated improvements in adherence and other patient outcomes. CONCLUSION The findings of the systematic review were consistent with the NCODA patient-centered standards for patient relationships and education, adherence, safety, collection of data, documentation, and other areas. NCODA standards were adopted and used as basis for these American Society of Clinical Oncology/NCODA standards. Additional information is available at www.asco.org/mid-standards .
Bridging the Gap: A Priorities Assessment Tool to Support Shared Decision Making, Maximize Appointment Time, and Increase Patient Satisfaction in Women With Ovarian Cancer
Authors: Frey Melissa K. , Ellis Annie , Shyne Savannah , Kahn Ryan , Chapman-Davis Eloise , Blank Stephanie V. 
Published: December 2019

PURPOSE: Women with ovarian cancer identify patient-physician communication as an essential element in determining treatment course and believe a discussion about goals and values should precede treatment decisions. We sought to develop a patient-centered priorities assessment tool for women with ovarian cancer that could streamline communication, enhance treatment discussions, and increase patient satisfaction. MATERIALS AND METHODS: We designed a priorities assessment tool using a validated ovarian cancer symptom index (National Comprehensive Cancer Center–Functional Assessment of Cancer Therapy Ovarian Symptom Index-18) combined with an index to assess daily quality-of-life priorities. The tool was distributed to women with ovarian cancer in small focus group settings and online, followed by a postactivity feedback form. RESULTS: In this pilot study, 36 women completed the priorities assessment tool and 35 completed the postactivity feedback form between September 2015 and May 2016. All participants reported that the tool was easy to understand and comprehensive in scope. Twenty-nine participants (82.9%) completed the tool in 10 minutes or less. Most participants (n = 31, 86.1%) were able to stratify their priorities and identify 5 top treatment-related priorities. Participants who indicated that their goals and priorities had changed since diagnosis (n = 25, 69.4%) reported that the tool helped to identify current goals and priorities (22 [88%] of 25 participants) and would help them feel more comfortable participating in shared decision making with their medical team (21 [84%] of 25 participants). CONCLUSION: A patient-centered priorities assessment tool was easy to complete and viewed as comprehensive and useful in a pilot cohort of women with ovarian cancer. Use of a priorities assessment tool has the potential to enhance communication, promote shared decision making, and improve patient satisfaction.
Violência e privação de liberdade: um estudo sobre trajetórias juvenis a partir do Radar de Relações Interpessoais
Authors: Santos Lopes de Oliveira Maria Claudia , Rejanne Machado Kelita 
Published: December 2019

A psicologia cultural é um ramo da psicologia que constitui fértil matriz interpretativa para sustentar o trânsito analítico entre o macrocontexto histórico-cultural e institucional, e o microcontexto das relações interpessoais, a fim de se compreender, desde uma perspectiva idiográfica, a configuração de trajetórias de desenvolvimento de adolescentes autores de ato infracional. Discutimos três estudos de caso decorrentes de nove meses de imersão etnográfica, durante a qual foram utilizados diferentes dispositivos metodológicos para favorecer a construção de narrativas e representações gráficas das trajetórias de vida. No presente artigo, exploraremos um dos instrumentos, denominado Radar de Relações Interpessoais (RRI). Os resultados produzidos pelo RRI apontam que as me- didas socioeducativas não promovem a ressocialização dos jovens, despreparam-nos para a participação social e contribuem para afastá-los das redes significativas previamente existentes. Por outro lado, o apoio recebido de diferentes atores institucionais foi percebido como promovendo tênue proteção, que deixa de existir quan- do são liberados. A existência de Outros significativos, catalisadores de trajetórias saudáveis e da projeção de futuros possíveis dentro e fora da internação, foi per- cebido como importante para o alcance de trajetórias de desenvolvimento desvinculadas da infração.
BENEFÍCIOS DAS ATIVIDADES AQUÁTICAS PARA IDOSOS
Authors: Leão Luciano Amado , Luciano Gilberto Aparecido Gomes , Santana Yasmin Barros de , Bonfim Mariana Rotta 
Published: December 2019

Introdução: Os profissionais da educação física devem estar sempre atualizados sobre os efeitos da prática de atividades aquáticas na saúde física, mental e emocional dos idosos, visando a melhoria de sua qualidade de vida, condição de saúde e bem-estar. Objetivo: Identificar as mais recentes evidências nacionais sobre os benefícios da prática de atividades aquáticas na vida dos idosos. Métodos: Revisão bibliográfica cujo levantamento dos trabalhos foi realizado nas bases de dados SciELO e LILACS, utilizando as combinações dos termos “Idoso(s)”, “atividades aquáticas”, “hidroginástica” e “natação”, publicados no período de Agosto de 2013 a Setembro de 2018. Resultados: A prática de hidroginástica e de fisioterapia aquática altera positiva e significativamente a performance dos idosos nos testes de equilíbrio e de flexibilidade quando comparados aos sedentários, porém não está associada a bons índices de força muscular. A fisioterapia aquática contribui para a melhora dos quadros de dor e da capacidade funcional na osteoartrite de joelho, e melhorou o desempenho no teste de 6 minutos dos idosos; porém, os praticantes de dança apresentaram melhor desempenho que os praticantes de hidroginástica. Conclusão: As atividades aquáticas de hidroginástica e hidroterapia contribuem para manutenção e melhora da flexibilidade, equilíbrio e capacidade funcional dos idosos; apesar de melhorarem a dor na oesteoartrite de joelho, não estão associadas a bons índices de força muscular de membros inferiores.
Surface treatments of dielectric laser accelerators for increased laser-induced damage threshold
Authors: Miao Yu , Black Dylan S. , Leedle Kenneth J. , Zhao Zhexin , Deng Huiyang , Ceballos Andrew , Byer Robert L. , Harris James S. , Solgaard Olav 
Published: December 2019

This paper describes two surface treatments for silicon dual-pillar dielectric laser accelerators (DLAs), which increase the laser-induced damage threshold (LIDT) and therefore the maximum achievable acceleration gradient. Hydrogen annealing reduces the surface roughness of the silicon pillars and mesa, making the LIDT less dependent on surface perturbations incurred during fabrication, as well as causing damage to occur at predictable locations. Hydrogen annealing decreases the range of the measured LIDT from

5.3
−
10

m
J

/

c

m
2

to

9.5
−
10.2

m
J

/

c

m
2

with 1960 nm 300 fs pulses. Additionally, 90 nm of low-stress silicon nitride film coating on the annealed DLA improves the damage fluence by 27%. Smoother interfaces, possibly combined with charge transfer from the pillars to the nitride coating, decrease the range of the LIDT and increase the damage fluence. The surface-treated DLAs accelerate 97 keV electrons with an acceleration gradient of

178
±
1.8

M
e
V

/

m

, an increase of 11% over the previous maximal gradient achieved with dual-pillar DLAs.
Carmen Alemany Bay (ed.). Las ficciones heterodoxas de Margo Glantz. Visiones críticas. Madrid: Visor, 2018
Authors: Jiménez Ríos Laura 
Published: December 2019

Esta reseña evalúa el volumen editado por Carmen Alemany Bay: Las ficciones heterodoxas de Margo Glantz. Visiones críticas, publicado por Visor en 2018, 400 pp. ISBN: 9788498952124.
Analisis Inkonsistensi Penggunaan Lahan di Kawasan Lindung DAS Cisadane
Authors: Ianah Ianah 
Published: December 2019

Penelitian ini bertujuan untuk menganalisis kesesuaian pemanfaatan kawasan lindung dengan rencana pola ruang dan menganalisis faktor-faktor yang mempengaruhinya untuk selanjutanya dapat merumuskan arahan pengen­dalian pemanfaatan ruang di kawasan lindung DAS Cisadane Kabupaten Bogor. Analisis spasial digunakan untuk mendapatkan informasi tentang penggunaan lahan, kepemilikan lahan, izin lokasi, dan evaluasi penggunaan lahan terhadap rencana pola ruang. Metode kualitatif melalui wawancara untuk mengidentifikasi faktor-faktor yang mempengaruhi inkonsistensi penggunaan lahan terhadap rencana pola ruang melalui tumpang susun peta RTRW 2016-2036 dengan tutupan lahan 2016. Perumusan arahan pengendalian pemanfaatan ruang diperoleh dengan analisis deskriptif. Hasil penelitian menunjukkan bahwa ketidaksesuaian pemanfaatan lahan sebesar 22.7%, luas kawasan hutan yang tutupan hutan 25.35%. Faktorfaktor yang menyebabkan inkonsistensi karena ketidakpahaman masyarakat tentang rencana pola ruang kawasan lindung terutama yang bukan kawasan hutan, penegakan hukum yang lemah bagi pelanggaran ruang, kurangnya koordinasi dan transparansi dalam proses perizinan, kebutuhan lahan masyarakat sekitar hutan, Perubahan budaya bertani yang menurun dan fasilitas pertanian yang kurang men­dukung dan berpindahnya kepemilikan lahan. Oleh karena itu diperlukan instrument pengendalian melalui Trans­paransi, koordinasi dan integrasi dalam hal perizinan, RDTR perlu segera diselesaikan, pemberian insentif dan disinsentif, dan sanksi, menumbuhkan aksi bersama dalam melakukan pengawasan dan pengendalian pemanfaatan ruang.
La zarzuela costarricense
Authors: Le Franc Ureña Roberto 
Published: December 2019

La zarzuela es un género musical español que tuvo su origen en el siglo XVI. Se incluye dentro de las artes escénicas y básicamente se divide en zarzuela grande y en género chico. La época de su auge y esplendor fue en el siglo XIX.
En Costa Rica se conoce a partir de 1850. Posteriormente fueron recreadas por algunos compositores musicales nacionales ya que desde sus inicios tuvieron gran aceptación por ser obras escénico-musicales expresadas en idioma español.
Sin seguir estrictamente un criterio musicológico o técnico musical, este trabajo es más una recopilación de datos dispersos sobre los compositores nacionales que incursionaron en el campo de la zarzuela o de modestas obras escénico-musicales agrupadas como zarzuelas o como género chico, tan celebrado y gustado en España. Con lo anterior se quiso demostrar que en Costa Rica este género musical tuvo sus exponentes y que con muy buen tino dieron a los costarricenses lo mejor de su esfuerzo.
Provocation of life functions at a unicellular eukaryote level by extremely low doses of mammalian hormones: Evidences of hormesis
Authors: Csaba György 
Published: December 2019

Hormones, characteristic to higher ranked animals, are synthesized, stored, and secreted by unicellular eukaryote animals. The unicells also have receptors for recognizing these materials and transmit the message into the cells for provoking response. The hormones are effective in very low concentrations (down to 10–21 M) and opposite effects of lower and higher concentrations can be observed. However, sometimes linear concentration effects can be found, which means that hormesis exists, nevertheless uncertain, as it is in the phase of formation (evolutionary experimentation). Hormesis, by transformation (fixation) of cytoplasmic receptor-like membrane components to receptors in the presence of the given hormone, likely helps the development of unicellular endocrine character and by this the evolution of endocrine system. The effect by extremely low concentrations of hormones had been forced by the watery way of unicellular life, which could establish the physiological concentrations of hormones in the blood of higher ranked animals. This means that hormetic low doses are the normal, effective concentrations and the high concentrations are artificial, consequently could be dangerous.