bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Bactericidal Activity Levels Monitor to Guide Intravenous Dalbavancin Chronic Suppressive Therapy of Inoperable Staphylococcal Prosthetic Valve Endocarditis: A Case Report
Authors: Spaziante Martina , Franchi Cristiana , Taliani Gloria , D’Avolio Antonio , Pietropaolo Valeria , Biliotti Elisa , Esvan Rozenn , Venditti Mario 
Published: September 2019

AbstractHere we describe a case of a methicillin-resistant coagulase-negative staphylococci prosthetic valve endocarditis in a patient considered not eligible for valve replacement due to high perioperative mortality risk and who did not tolerate oral antibiotic treatment. Under these circumstances, intravenous long-term chronic suppressive antibiotic therapy with dalbavancin, scheduling the doses using the serum bactericidal activity titers, proved to be safe and effective.
Metastatic spinal cord compression by gastric cancer: a case report
Authors: Kawahigashi Teiko , Kawabe Takashi , Iijima Hirokazu , Igarashi Yuto , Suno Yuma , Takagi Mutsuo , Yamaji Fuminori , Watanabe Kazunao 
Published: September 2019

Abstract
Metastatic spinal cord compression (MSCC) is one of the serious complications of malignancy. Most cases of MSCC occur from breast or prostate cancer primaries; MSCC secondary to gastric cancer is rare. We herein report a case of a patient with gastric cancer with weakness of the lower limbs and urinary retention on initial presentation. This case demonstrates that although rare, bone metastases and MSCC may occur from gastric primaries. It also highlights the importance of prompt diagnosis and early treatment of MSCC.
Efficiency evaluation of S&T resource allocation using an accurate quantification of the time-lag effect and relation effect: a case study of Chinese research institutes
Authors: Yue Weizhen , Gao Jun , Suo Weilan 
Published: September 2019

Abstract
Efficiency evaluation is a significant means of judging the allocation quality of science and technology (S&T) resource. In reality, the process of S&T resource allocation is accompanied by the time-lag effect and relation effect, and the effect differences among research institutes are obvious. In this study, we attempt to conduct efficiency evaluation of S&T resource allocation in Chinese research institutes using an accurate quantification of the time-lag effect and relation effect. A hybrid model for efficiency evaluation is designed, where the vector autoregression (VAR) model and the output revision model are adopted to quantify the time-lag effect and relation effect, and an extended super-efficiency data envelopment analysis (SE-DEA) model is proposed to conduct efficiency estimation under the quantified effects. Subsequently, a quantitative case study is conducted based on 30 sample institutes in the Chinese Academy of Sciences using statistical data from 1992 to 2014. The results indicate that the time-lag effect of each institute varies with the forms of outputs owing to the difference of individual transformation capability. The relation effect of each institute varies with the allocation proportions of inputs owing to the difference of individual developmental orientation. Compared with other methods, the proposed hybrid model can not only determine a discriminative ranking of the sample institutes, but also clarify the strengths and weaknesses of each institute. These main findings are beneficial for decision makers of sample institutes to realize the overall optimization of S&T resource allocation from the aspects of capability promotion, resource adjustment, and efficiency improvement.
Performance of ultra-high-frequency ultrasound in the evaluation of skin involvement in systemic sclerosis: a preliminary report
Authors: Naredo Esperanza , Pascau Javier , Damjanov Nemanja , Lepri Gemma , Gordaliza Pedro M , Janta Iustina , Ovalles-Bonilla Juan Gabriel , López-Longo Francisco Javier , Matucci-Cerinic Marco 
Published: September 2019

Abstract

Objective
High frequency ultrasound allows visualization of epidermis, dermis and hypodermis, precise measurement of skin thickness, as well as assessment of skin oedema, fibrosis and atrophy. The aim of this pilot cross-sectional observational study was to assess the performance and multiobserver variability of ultra-high-frequency (UHF) (50 MHz) ultrasound (US) in measuring skin thickness as well as the capacity of UHF-derived skin features to differentiate SSc patients from healthy controls.

Methods
Twenty-one SSc patients (16 limited and five diffuse SSc) and six healthy controls were enrolled. All subjects underwent US evaluation by three experts at three anatomical sites (forearm, hand and finger). Dermal thickness was measured and two rectangular regions of interest, one in dermis and one in hypodermis, were established for texture feature analysis.

Results
UHF-US allowed a precise identification and measurement of the thickness of the dermis. The dermal thickness in the finger was significantly higher in patients than in controls (P &lt; 0.05), while in the forearm it was significantly lower in patients than in controls (P &lt; 0.001). Interobserver variability for dermal thickness was good to excellent [forearm intraclass correlation coefficient (ICC) = 0.754; finger ICC = 0.699; hand ICC = 0.602]. Texture computed analysis of dermis and hypodermis was able to discriminate between SSc and healthy subjects (area under the curve &gt;0.7).

Conclusion
These preliminary data show that skin UHF-US allows a very detailed imaging of skin layers, a reliable measurement of dermal thickness, and a discriminative capacity between dermis and hypodermis texture features in SSc and healthy subjects.
Determinants of ferritin response to oral iron supplementation in children with sleep movement disorders
Authors: DelRosso Lourdes M , Yi Troy , Chan Jeremy H M , Wrede Joanna E , Lockhart Carey T , Ferri Raffaele 
Published: September 2019

Abstract

Study Objectives
To identify children who respond to oral iron supplementation as evidenced by increased ferritin levels and to identify factors that correlate with improvement in ferritin levels in those who respond.

Methods
A retrospective chart review of the PLMS/RLS/RSD database at Seattle Children’s Hospital was carried out. Data collected included nocturnal polysomnography parameters, age, sex, initial and follow-up ferritin level and date of collection, and presence of restless legs syndrome (RLS), periodic limb movements of sleep (PLMS)/PLM disorder (PLMD), restless sleep disorder (RSD), obstructive sleep apnea (OSA), neurologic, psychiatric, neurodevelopmental, or medical comorbidity. Oral iron therapy was evaluated by side effects (none; constipation; bad taste/nausea), subjective outcome in symptoms (resolved, improved, no change), and adherence to therapy (poor, fair, good).

Results
Seventy-seven children were included in this study of whom 42 were classified as responders (increase in ferritin of ≥10 µg/L) and 35 were nonresponders. Age and sex were not different between groups. Adherence was the only significant predictor of an increase in ferritin of ≥10 µg/L. Constipation was seen in 7.1% of responders vs. 45.8% of nonresponders. No change in symptoms was reported in 26.2% of responders vs. 71.4% in nonresponders. A significant correlation was found between treatment duration and ferritin level change in responders but not in nonresponders

Conclusions
Side effects hinders adherence to oral iron supplementation in children. Responders to oral iron show improvement in ferritin levels and symptoms, while nonresponders show no improvement in ferritin levels despite a long-lasting treatment, at least in part of them.
Striatal Nurr1 Facilitates the Dyskinetic State and Exacerbates Levodopa-Induced Dyskinesia in a Rat Model of Parkinson’s Disease
Authors: Sellnow RC , Steece-Collier K , Altwal F , Sandoval IM , Kordower JH , Collier TJ , Sortwell CE , West AR , Manfredsson FP 
Published: September 2019

AbstractBackgroundThe transcription factor Nurr1 has been identified to be ectopically induced in the striatum of dyskinetic rodents expressing L-DOPA-induced dyskinesia (LID). In the present study, we sought to characterize Nurr1 as a causative factor in LID expression.MethodsWe used rAAV2/5 to overexpress Nurr1 or GFP in the parkinsonian striatum of LID-resistant Lewis or LID-prone Fischer-344 (F344) rats. In a second cohort, rats received the Nurr1 agonist amodiaquine (AQ) together with L-DOPA or ropinirole. All rats received a chronic DA agonist and were evaluated for LID severity. Finally, we performed single unit recordings and dendritic spine analyses in drug-naïve rAAV-injected parkinsonian rats.ResultsrAAV-GFP injected LID-resistant Lewis rats displayed mild LID and no induction of striatal Nurr1. However, Lewis rats transduced to overexpress Nurr1 developed severe LID. Nurr11 agonism with AQ exacerbated LID in F344 rats. We additionally determined that in L-DOPA-naïve rats striatal rAAV-Nurr1 overexpression 1) increased firing activity in dopamine-depleted striatal direct pathway neurons, and 2) decreased spine density and thin-spine morphology on striatal medium spiny neurons, mimicking changes seen in dyskinetic rats. Finally, we provide post-mortem evidence of Nurr1 expression in the striatum of L-DOPA treated PD patients.ConclusionsOur data demonstrate that ectopic induction of striatal Nurr1 is capable of inducing LID behavior and associated neuropathology, even in resistant subjects. These data support a direct role of Nurr1 in aberrant neuronal plasticity and LID induction, providing a potential novel target for therapeutic development.
Genetic factor for twisting legume pods identified by fine-mapping of shattering-related traits in azuki bean and yard-long bean
Authors: Takahashi Yu , Kongjaimun Alisa , Muto Chiaki , Kobayashi Yuki , Kumagai Masahiko , Sakai Hiroaki , Satou Kazuhito , Teruya Kuniko , Shiroma Akino , Shimoji Makiko , Hirano Takashi , Isemura Takehisa , Saito Hiroki , Baba-Kasai Akiko , Kaga Akito , Somta Prakit , Tomooka Norihiko , Naito Ken 
Published: September 2019

SUMMARYLegumes have evolved a unique manner of seed dispersal in that the seed pods explosively split open with helical tension generated by sclerenchyma on the endocarp. During domestication, azuki bean (Vigna angularis) and yard-long bean (Vigna unguiculata cv-gr. Sesquipedalis) have reduced or lost the sclerenchyma and lost the shattering behavior of seed pods. Here we performed fine-mapping with back-crossed populations and narrowed the candidate genomic region down to 4 kbp in azuki bean and 13 kbp in yard-long bean. Among genes located in these regions, we found MYB26 genes encoded truncated proteins in both the domesticated species. We also found in azuki bean and other legumes that MYB26 is duplicated and only the duplicated copy is expressed in seed pods. Interestingly, in Arabidopsis MYB26 is single copy and is specifically expressed in anther to initiate secondary wall thickening that is required for anther dehiscence. These facts indicated that, in legumes, MYB26 has been duplicated and acquired a new role in development of pod sclerenchyma. However, pod shattering is unfavorable phenotype for harvesting and thus has been selected against by human.
Defective excitatory/inhibitory synaptic balance and increased neuron apoptosis in a zebrafish model of Dravet syndrome
Authors: Brenet Alexandre , Hassan-Abdi Rahma , Somkhit Julie , Yanicostas Constantin , Soussi-Yanicostas Nadia 
Published: September 2019

AbstractDravet syndrome is a type of severe childhood epilepsy that responds poorly to current anti-epileptic drugs. In recent years, zebrafish disease models with Scn1Lab sodium channel deficiency have been generated to seek novel anti-epileptic drug candidates, some of which are currently undergoing clinical trials. However, the spectrum of neuronal deficits observed following Scn1Lab depletion in zebrafish larvae has not yet been fully explored. To fill this gap and gain a better understanding of the mechanisms underlying neuron hyperexcitation in Scn1Lab-depleted larvae, we analyzed neuron activity in vivo using combined local field potential recording and transient calcium uptake imaging, studied the distribution of excitatory and inhibitory synapses and neurons as well as investigated neuron apoptosis. We found that Scn1Lab-depleted larvae displayed recurrent epileptiform seizure events, associating massive synchronous calcium uptakes and ictal-like local field potential bursts. Scn1Lab-depletion also caused a dramatic shift in the neuronal and synaptic balance toward excitation and increased neuronal death. Our results thus provide in vivo evidence suggesting that Scn1Lab loss of function causes neuron hyperexcitation as the result of disturbed synaptic balance and increased neuronal apoptosis.
miRNA858b Inhibits Proanthocyanidin Accumulation by Repression ofDkMYB19andDkMYB20in Persimmon
Authors: Yang Sichao , Zhang Meng , Xu Liqing , Luo Zhengrong , Zhang Qinglin 
Published: September 2019

AbstractPersimmon proanthocyanidin (PA) biosynthetic had been reported to be regulated by several transcription factors, but the miRNAs function involved in this process was poorly understood. We identified a miRNA858b that putatively targeted two R2R3-MYB transcription factors,DkMYB19/DkMYB20. Transcript accumulation ofDkMYB19/DkMYB20and miRNA858b showed contrasting divergent expression patterns during fruit development. DkMYB19/DkMYB20 were confirmed to be localized in the nucleus. The interaction between miRNA858b andDkMYB19/DkMYB20were experimentally validated by 5’ RNA ligase-mediated RACE and LUC enzyme activity detection. Overexpression of miRNA858b led to the down-regulation ofDkMYB19/DkMYB20which reduced the accumulation of PA, whereas the reduced miRNA858b activity that up-regulated theDkMYB19/DkMYB20resulted in high levels of PA in STTM858b transient expression in leavesin vivo. Similarly, the transient transformation of miRNA858b in fruit wafersin vitroalso reduced the accumulation of PA by repressing theDkMYB19/DkMYB20, while the up-regulation ofDkMYB19/DkMYB20enhanced the accumulation of PA in STTM858b orDkMYB19/DkMYB20transient transformation in fruit wafers. PA content decreased after overexpression of miRNA858b inArabidopsiswild type andDkMYB19/DkMYB20in persimmon leaf callus consisted with the above results. These findings suggested that miRNA858b repressed the expression ofDkMYB19/DkMYB20which contribute to PA accumulation in persimmon.
Hepatic JNK-mediated bile acid homeostasis regulates liver cancer through PPARα
Authors: Manieri Elisa , Esteban-Lafuente Laura , Rodríguez María Elena , Leiva-Vega Luis , Chen Chaobo , Cubero Francisco Javier , Barrett Tamera , Cavanagh-Kyros Julie , Seruggia Davide , Monte Maria J. , Marin Jose J.G. , Davis Roger J. , Mora Alfonso , Sabio Guadalupe 
Published: September 2019

ABSTRACTcJun NH2-terminal kinase (JNK) inhibition has been suggested as a potential treatment for insulin resistance and steatosis through activation of the transcription factor PPARα. However, the long-term consequences have not been evaluated. We found that hepatic JNK deficiency alters bile acid and cholesterol metabolism, resulting in hepatic expression of FGF15 and activation of ERK in cholangiocytes, which ultimately promotes their proliferation. Genetic inactivation of PPARα identifies PPARα hyperactivation as the molecular mechanism for these deleterious effects. Our analysis indicates that hepatic PPARα activation is oncogenic: PPARα deficiency protects mice against carcinogen-induced hepatocellular carcinoma under high fat diet (HFD) condition. These surprising results urge the re-consideration of using JNK inhibitors or PPAR agonists for the treatment of metabolic syndrome.
Admixture-enabled selection for rapid adaptive evolution in the Americas
Authors: Norris Emily T. , Rishishwar Lavanya , Chande Aroon T. , Conley Andrew B. , Ye Kaixiong , Valderrama-Aguirre Augusto , King Jordan I. 
Published: September 2019

AbstractBackgroundAdmixture occurs when previously isolated populations come together and exchange genetic material. We hypothesized that admixture can enable rapid adaptive evolution in human populations by introducing novel genetic variants (haplotypes) at intermediate frequencies, and we tested this hypothesis via the analysis of whole genome sequences sampled from admixed Latin American populations in Colombia, Mexico, Peru, and Puerto Rico.ResultsOur screen for admixture-enabled selection relies on the identification of loci that contain more or less ancestry from a given source population than would be expected given the genome-wide ancestry frequencies. We employed a combined evidence approach to evaluate levels of ancestry enrichment at (1) single loci across multiple populations and (2) multiple loci that function together to encode polygenic traits. We found cross-population signals of African ancestry enrichment at the major histocompatibility locus on chromosome 6, consistent with admixture-enabled selection for enhanced adaptive immune response. Several of the human leukocyte antigen genes at this locus (HLA-A,HLA-DRB51andHLA-DRB5) showed independent evidence of positive selection prior to admixture, based on extended haplotype homozygosity in African populations. A number of traits related to inflammation, blood metabolites, and both the innate and adaptive immune system showed evidence of admixture-enabled polygenic selection in Latin American populations.ConclusionsThe results reported here, considered together with the ubiquity of admixture in human evolution, suggest that admixture serves as a fundamental mechanism that drives rapid adaptive evolution in human populations.
Systematic assessment of regulatory effects of human disease variants in pluripotent cells
Authors: Bonder Marc Jan , Smail Craig , Gloudemans Michael J. , Frésard Laure , Jakubosky David , D’Antonio Matteo , Li Xin , Ferraro Nicole M. , Carcamo-Orive Ivan , Mirauta Bogdan , Seaton Daniel D. , Cai Na , Horta Danilo ,   HipSci Consortium,   iPSCORE Consortium,   GENESiPS Consortium,   PhLiPS Consortium, Smith Erin N. , Frazer Kelly A. , Montgomery Stephen B. , Stegle Oliver 
Published: September 2019

AbstractIdentifying regulatory genetic effects in pluripotent cells provides important insights into disease variants with potentially transient or developmental origins. Combining existing and newly-generated data, we characterized 1,367 iPSC lines from 948 unique donors, collectively analyzed within the “Integrated iPSC QTL” (i2QTL) Consortium. The sample size of our study allowed us to derive the most comprehensive map of quantitative trait loci (QTL) in pluripotent human cells to date. We mapped the effects of nearby common genetic variants on five expression phenotypes, identifying cis-QTL at gene-, exon-level and transcript-, splicing-, alternative polyadenylation-ratio (APA) for a total of 18,556 genes. For gene-level, we further quantified the effects of rare and singleton variants, and the effect of distal variants that act in trans (trans-eQTL), which we replicated in independent samples. Our data are a valuable community resource, uncovering novel regulatory effects that have not previously been described in differentiated cells and tissues. Building on this regulatory map, we functionally explore GWAS signals for over 4,336 trait loci, finding evidence for colocalization with common and rare iPSC QTL for traits such as height and BMI, and diseases, such as cancer and coronary artery disease.
X chromosome inactivation in the human placenta is patchy and distinct from adult tissues
Authors: Phung Tanya N. , Olney Kimberly C. , Silasi Michelle , Perley Lauren , O’Bryan Jane , Kliman Harvey J. , Wilson Melissa A. 
Published: September 2019

AbstractOne of the X chromosomes in genetic females is silenced by a process called X chromosome inactivation (XCI). Variation in XCI across the placenta may contribute to observed sex differences and variability in pregnancy outcomes. However, XCI has predominantly been studied in human adult tissues. Here we sequenced and analyzed DNA and RNA from two locations from 30 full-term pregnancies. Implementing an allele specific approach to examine XCI, we report evidence that XCI in the human placenta is patchy, with large patches of either silenced maternal or paternal X chromosomes. Further, using similar measurements, we show that this is in contrast to adult tissues, which generally exhibit mosaic X-inactivation, where bulk samples exhibit both maternal and paternal X chromosome expression. Further, by comparing skewed samples in placenta and adult tissues, we identify genes that are uniquely silenced or expressed in the placenta compared to adult tissues highlighting the need for tissue-specific maps of XCI.
Prevalent pH Controls the Capacity of Galdieria Maxima to Use Ammonia and Nitrate as a Nitrogen Source
Authors: Iovinella M. , Carbone DA. , Cioppa D. , Davis S.J. , Innangi M. , Esposito S. , Ciniglia C. 
Published: September 2019

ABSTRACTGaldieria maxima is a polyextremophilic alga capable of diverse metabolic processes. Ammonia is widely used in culture media typical of laboratory growth. Recent reports that this species can grow on wastes promote the concept that G. maxima might have biotechnological utility. Accordingly, there is a need to know the range of pH levels that can support G. maxima growth in a given nitrogen source. Here, we examined the combined effect of pH and nitrate/ammonium source on the growth and long-term response of the photochemical process to a pH gradient in different G. maxima strains. All were able to use differing nitrogen sources, despite both the growth rate and photochemical activity were significantly affected by the combination with the pH. All strains acidified the NH4+-medium (pH<3); only G. maxima IPPAS P507 showed reduced capacity in lowering the pH from 6.5. pH was a limiting factor in nitrate uptake at pH≥6.5; noteworthy, at pH 5 on nitrate G. maxima ACUF551 showed a good growth performance, despite the alkalization of the medium.
A new role of the Mus81 nuclease for replication completion after fork restart
Authors: Pardo Benjamin , Moriel-Carretero María , Vicat Thibaud , Aguilera Andrés , Pasero Philippe 
Published: September 2019

ABSTRACTImpediments to DNA replication threaten genome stability. The homologous recombination (HR) pathway is involved in the restart of blocked replication forks. Here, we used a new method to study at the molecular level the restart of replication in response to DNA topoisomerase I poisoning by camptothecin (CPT). We show that HR-mediated restart at the global genomic level occurs by a BIR-like mechanism that requires Rad52, Rad51 and Pol32. The Mus81 endonuclease, previously proposed to cleave blocked forks, is not required for replication restart in S phase but appears to be essential to resolve fork-associated recombination intermediates in G2/M as a step necessary to complete replication. We confirmed our results using an independent system that allowed us to conclude that this mechanism is independent of the accumulation of DNA supercoiling and DNA-protein crosslinks normally caused by CPT. Thus, we describe here a specific function for Mus81 in the processing of HR-restarted forks required to complete DNA replication.