bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of Global Grassland Net Ecosystem Carbon Exchange Using a Model Tree Ensemble Approach
Authors: Liang Wei , Zhang Weibin , Jin Zhao , Yan Jianwu , Lü Yihe , Wang Shuai , Fu Bojie , Li Shuai , Ji Qiulei , Gou Fen , Fu Shuyi , An Shantao , Wang Fengjiao 
Published: December 2019

AbstractUnderstanding the net ecosystem CO2 exchange (NEE) between terrestrial ecosystems and the atmosphere is crucial for accurate estimation of carbon budgets, which remains unclear for grassland ecosystems. Here we upscaled site‐level NEE from 44 grassland flux towers (1,457 site‐months) to the global scale by using a model tree ensemble approach that considers the management activities (grazing and cutting) (MTE‐GM). Cross‐validation showed that MTE‐GM performs reasonably well in terms of among‐site variability and seasonal variation, with a Nash‐Sutcliffe efficiency of 0.90 and 0.86 and an R2 of 0.91 and 0.86, respectively. Radiation (shortwave and longwave), temperature, leaf area index, and fraction of absorbed photosynthetic active radiation had the highest relative explanatory power in predicting NEE. Based on MTE‐GM, mean annual NEE of global grassland was 72 ± 4 g C m−2 year−1 (1.9 ± 0.11 Pg C year−1) during 1982–2011, suggesting that the grassland ecosystems have been acting as a small carbon source during the past three decades. However, grasslands in temperate and continental regions had the largest carbon sink of −61.9 ± 5.7 and −51.8 ± 7.9 g C m−2 year−1, respectively. Moreover, we found that elimination of grassland management effect resulted in an extra emission of 1.7% CO2 to the atmosphere (CO2 sink from the management is 0.03 Pg C year−1). From the 1980s to the 2000s, 38% (22%) and 17% (18%) of pixels showed an increased (decreased) carbon uptake and decreased (increased) carbon release, respectively. Uncertainty assessment suggested that there would be higher confidence in NEE estimates in most parts of middle‐ to high‐latitude regions in the Northern Hemisphere.
Phase 2 study of vismodegib, a hedgehog inhibitor, combined with gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic adenocarcinoma
Authors: De Jesus-Acosta Ana , Sugar Elizabeth A. , O’Dwyer Peter J. , Ramanathan Ramesh K. , Von Hoff Daniel D. , Rasheed Zeshaan , Zheng Lei , Begum Asma , Anders Robert , Maitra Anirban , McAllister Florencia , Rajeshkumar N. V. , Yabuuchi Shinichi , de Wilde Roeland F. , Batukbhai Bhavina , Sahin Ismet , Laheru Daniel A. 
Published: December 2019

Abstract
Background
The Hedgehog (Hh) signalling pathway is overexpressed in pancreatic ductal adenocarcinoma (PDA). Preclinical studies have shown that Hh inhibitors reduce pancreatic cancer stem cells (pCSC), stroma and Hh signalling.

Methods
Patients with previously untreated metastatic PDA were treated with gemcitabine and nab-paclitaxel. Vismodegib was added starting on the second cycle. The primary endpoint was progression-free survival (PFS) as compared with historical controls. Tumour biopsies to assess pCSC, stroma and Hh signalling were obtained before treatment and after cycle 1 (gemcitabine and nab-paclitaxel) or after cycle 2 (gemcitabine and nab-paclitaxel plus vismodegib).

Results
Seventy-one patients were enrolled. Median PFS and overall survival (OS) were 5.42 months (95% confidence interval [CI]: 4.37–6.97) and 9.79 months (95% CI: 7.85–10.97), respectively. Of the 67 patients evaluable for response, 27 (40%) had a response: 26 (38.8%) partial responses and 1 complete response. In the tumour samples, there were no significant changes in ALDH + pCSC following treatment.

Conclusions
Adding vismodegib to chemotherapy did not improve efficacy as compared with historical rates observed with chemotherapy alone in patients with newly diagnosed metastatic pancreatic cancer. This study does not support the further evaluation of Hh inhibitors in this patient population.

Trial registration
ClinicalTrials.gov Identifier: NCT01088815.
El Niño-Southern oscillation and under-5 diarrhea in Botswana
Authors: Heaney Alexandra K. , Shaman Jeffrey , Alexander Kathleen A. 
Published: December 2019

AbstractChildhood diarrheal disease causes significant morbidity and mortality in low and middle-income countries, yet our ability to accurately predict diarrhea incidence remains limited. El Niño-Southern Oscillation (ENSO) has been shown to affect diarrhea dynamics in South America and Asia. However, understanding of its effects in sub-Saharan Africa, where the burden of under-5 diarrhea is high, remains inadequate. Here we investigate the connections between ENSO, local environmental conditions, and childhood diarrheal disease in Chobe District, Botswana. Our results demonstrate that La Niña conditions are associated with cooler temperatures, increased rainfall, and higher flooding in the Chobe region during the rainy season. In turn, La Niña conditions lagged 0–5 months are associated with higher than average incidence of under-5 diarrhea in the early rainy season. These findings demonstrate the potential use of ENSO as a long-lead prediction tool for childhood diarrhea in southern Africa.
Evolution of satellite plasmids can prolong the maintenance of newly acquired accessory genes in bacteria
Authors: Zhang Xue , Deatherage Daniel E. , Zheng Hao , Georgoulis Stratton J. , Barrick Jeffrey E. 
Published: December 2019

AbstractTransmissible plasmids spread genes encoding antibiotic resistance and other traits to new bacterial species. Here we report that laboratory populations of Escherichia coli with a newly acquired IncQ plasmid often evolve ‘satellite plasmids’ with deletions of accessory genes and genes required for plasmid replication. Satellite plasmids are molecular parasites: their presence reduces the copy number of the full-length plasmid on which they rely for their continued replication. Cells with satellite plasmids gain an immediate fitness advantage from reducing burdensome expression of accessory genes. Yet, they maintain copies of these genes and the complete plasmid, which potentially enables them to benefit from and transmit the traits they encode in the future. Evolution of satellite plasmids is transient. Cells that entirely lose accessory gene function or plasmid mobility dominate in the long run. Satellite plasmids also evolve in Snodgrassella alvi colonizing the honey bee gut, suggesting that this mechanism may broadly contribute to the importance of IncQ plasmids as agents of bacterial gene transfer in nature.
An Abl-FBP17 mechanosensing system couples local plasma membrane curvature and stress fiber remodeling during mechanoadaptation
Authors: Echarri Asier , Pavón Dácil M. , Sánchez Sara , García-García María , Calvo Enrique , Huerta-López Carla , Velázquez-Carreras Diana , Viaris de Lesegno Christine , Ariotti Nicholas , Lázaro-Carrillo Ana , Strippoli Raffaele , De Sancho David , Alegre-Cebollada Jorge , Lamaze Christophe , Parton Robert G. , Del Pozo Miguel A. 
Published: December 2019

AbstractCells remodel their structure in response to mechanical strain. However, how mechanical forces are translated into biochemical signals that coordinate the structural changes observed at the plasma membrane (PM) and the underlying cytoskeleton during mechanoadaptation is unclear. Here, we show that PM mechanoadaptation is controlled by a tension-sensing pathway composed of c-Abl tyrosine kinase and membrane curvature regulator FBP17. FBP17 is recruited to caveolae to induce the formation of caveolar rosettes. FBP17 deficient cells have reduced rosette density, lack PM tension buffering capacity under osmotic shock, and cannot adapt to mechanical strain. Mechanistically, tension is transduced to the FBP17 F-BAR domain by direct phosphorylation mediated by c-Abl, a mechanosensitive molecule. This modification inhibits FBP17 membrane bending activity and releases FBP17-controlled inhibition of mDia1-dependent stress fibers, favoring membrane adaptation to increased tension. This mechanoprotective mechanism adapts the cell to changes in mechanical tension by coupling PM and actin cytoskeleton remodeling.
Agreement between two large pan-cancer CRISPR-Cas9 gene dependency data sets
Authors: Dempster Joshua M. , Pacini Clare , Pantel Sasha , Behan Fiona M. , Green Thomas , Krill-Burger John , Beaver Charlotte M. , Younger Scott T. , Zhivich Victor , Najgebauer Hanna , Allen Felicity , Gonçalves Emanuel , Shepherd Rebecca , Doench John G. , Yusa Kosuke , Vazquez Francisca , Parts Leopold , Boehm Jesse S. , Golub Todd R. , Hahn William C. , Root David E. , Garnett Mathew J. , Tsherniak Aviad , Iorio Francesco 
Published: December 2019

AbstractGenome-scale CRISPR-Cas9 viability screens performed in cancer cell lines provide a systematic approach to identify cancer dependencies and new therapeutic targets. As multiple large-scale screens become available, a formal assessment of the reproducibility of these experiments becomes necessary. We analyze data from recently published pan-cancer CRISPR-Cas9 screens performed at the Broad and Sanger Institutes. Despite significant differences in experimental protocols and reagents, we find that the screen results are highly concordant across multiple metrics with both common and specific dependencies jointly identified across the two studies. Furthermore, robust biomarkers of gene dependency found in one data set are recovered in the other. Through further analysis and replication experiments at each institute, we show that batch effects are driven principally by two key experimental parameters: the reagent library and the assay length. These results indicate that the Broad and Sanger CRISPR-Cas9 viability screens yield robust and reproducible findings.
Dual microglia effects on blood brain barrier permeability induced by systemic inflammation
Authors: Haruwaka Koichiro , Ikegami Ako , Tachibana Yoshihisa , Ohno Nobuhiko , Konishi Hiroyuki , Hashimoto Akari , Matsumoto Mami , Kato Daisuke , Ono Riho , Kiyama Hiroshi , Moorhouse Andrew J. , Nabekura Junichi , Wake Hiroaki 
Published: December 2019

AbstractMicroglia survey brain parenchyma, responding to injury and infections. Microglia also respond to systemic disease, but the role of blood–brain barrier (BBB) integrity in this process remains unclear. Using simultaneous in vivo imaging, we demonstrated that systemic inflammation induces CCR5-dependent migration of brain resident microglia to the cerebral vasculature. Vessel-associated microglia initially maintain BBB integrity via expression of the tight-junction protein Claudin-5 and make physical contact with endothelial cells. During sustained inflammation, microglia phagocytose astrocytic end-feet and impair BBB function. Our results show microglia play a dual role in maintaining BBB integrity with implications for elucidating how systemic immune-activation impacts neural functions.
Descending motor circuitry required for NT-3 mediated locomotor recovery after spinal cord injury in mice
Authors: Han Qi , Ordaz Josue D. , Liu Nai-Kui , Richardson Zoe , Wu Wei , Xia Yongzhi , Qu Wenrui , Wang Ying , Dai Heqiao , Zhang Yi Ping , Shields Christopher B. , Smith George M. , Xu Xiao-Ming 
Published: December 2019

AbstractLocomotor function, mediated by lumbar neural circuitry, is modulated by descending spinal pathways. Spinal cord injury (SCI) interrupts descending projections and denervates lumbar motor neurons (MNs). We previously reported that retrogradely transported neurotrophin-3 (NT-3) to lumbar MNs attenuated SCI-induced lumbar MN dendritic atrophy and enabled functional recovery after a rostral thoracic contusion. Here we functionally dissected the role of descending neural pathways in response to NT-3-mediated recovery after a T9 contusive SCI in mice. We find that residual projections to lumbar MNs are required to produce leg movements after SCI. Next, we show that the spared descending propriospinal pathway, rather than other pathways (including the corticospinal, rubrospinal, serotonergic, and dopaminergic pathways), accounts for NT-3-enhanced recovery. Lastly, we show that NT-3 induced propriospino-MN circuit reorganization after the T9 contusion via promotion of dendritic regrowth rather than prevention of dendritic atrophy.
Attribute driven inverse materials design using deep learning Bayesian framework
Authors: Tagade Piyush M. , Adiga Shashishekar P. , Pandian Shanthi , Park Min Sik , Hariharan Krishnan S. , Kolake Subramanya Mayya 
Published: December 2019

AbstractMuch of computational materials science has focused on fast and accurate forward predictions of materials properties, for example, given a molecular structure predict its electronic properties. This is achieved with first principles calculations and more recently through machine learning approaches, since the former is computation-intensive and not practical for high-throughput screening. Searching for the right material for any given application, though follows an inverse path—the desired properties are given and the task is to find the right materials. Here we present a deep learning inverse prediction framework, Structure Learning for Attribute-driven Materials Design Using Novel Conditional Sampling (SLAMDUNCS), for efficient and accurate prediction of molecules exhibiting target properties. We apply this framework to the computational design of organic molecules for three applications, organic semiconductors for thin-film transistors, small organic acceptors for solar cells and electrolyte additives with high redox stability. Our method is general enough to be extended to inorganic compounds and represents an important step in deep learning based completely automated materials discovery.
Neural correlates of tactile simultaneity judgement: a functional magnetic resonance imaging study
Authors: Kimura Takahiro , Kadota Hiroshi , Kuroda Tsuyoshi , Funai Tomomi D. , Iwata Makoto , Kochiyama Takanori , Miyazaki Makoto 
Published: December 2019

AbstractSimultaneity judgement (SJ) is a temporal discrimination task in which the targets span an ultimately short time range (zero or not). Psychophysical studies suggest that SJ is adequate to probe the perceptual components of human time processing in pure form. Thus far, time-relevant neural correlates for tactile SJ are unclear. We performed functional magnetic resonance imaging (fMRI) to investigate the neural correlates of tactile SJ using tactile number judgement as a time-irrelevant control task. As our main result, we demonstrated that the right inferior parietal lobule (IPL) is an SJ-specific region. The right IPL was detected by both parametric and non-parametric statistical analyses, and its activation intensity fulfilled a strict statistical criterion. In addition, we observed that some left-dominant regions (e.g., the striatum) were specifically activated by successive stimuli during SJ. Meanwhile, no region was specifically activated by simultaneous stimuli during SJ. Accordingly, we infer that the neural process for tactile SJ is as follows: the striatum estimates the time interval between tactile stimuli; based on this interval, the right IPL discriminates the successiveness or simultaneity of the stimuli. Moreover, taking detailed behavioural results into account, we further discuss possible concurrent or alternative mechanisms that can explain the fMRI results.
Optimized Measurement Parameters of Sensory Evoked Cortical Potentials to Assess Human Bladder Afferents - A Randomized Study
Authors: van der Lely Stéphanie , Liechti Martina D. , Schmidhalter Melanie R. , Schubert Martin , Bachmann Lucas M. , Kessler Thomas M. , Mehnert Ulrich 
Published: December 2019

AbstractOveractive bladder and voiding dysfunction are highly prevalent and often associated with malfunction of the bladder afferent pathways. Appropriate diagnostic tools for an objective assessment of afferent nerve function of the human bladder are currently missing. One promising possibility is the assessment of sensory evoked potentials (SEP) during repetitive electrical bladder stimulation, which proved feasible in healthy subjects. For an implementation into clinical practice, however, further refinements for efficient and reliable data acquisition are crucial. The aim of this randomized study was to find the optimal measurement settings regarding stimulation frequency, repetition number, and data acquisition. Forty healthy subjects underwent two visits of SEP (Cz-Fz) assessments using repetitive (500 stimuli) electrical stimulation of 0.5 Hz, 1.1 Hz, and 1.6 Hz and pulse width of 1 ms at the bladder dome or trigone. SEP analyses revealed higher amplitudes and better signal-to-noise ratio (SNR) with lower stimulation frequencies, while latencies remained unchanged. Decreasing amplitudes and SNR were observed with continuing stimulation accompanied by decreasing responder rate (RR). When applying stimuli at a frequency of 0.5 Hz, averaging across 200 stimuli revealed optimal reliability with best SNR, RR and sufficiently high amplitudes. This constitutes an optimal compromise between the duration of the assessment and SEP peak-to-peak amplitudes.
Long-term effectiveness and safety of varenicline and nicotine replacement therapy in people with neurodevelopmental disorders: A prospective cohort study
Authors: Itani Taha , Rai Dheeraj , Jones Tim , Taylor Gemma M. J. , Thomas Kyla H. , Martin Richard M. , Munafò Marcus R. , Davies Neil M. , Taylor Amy E. 
Published: December 2019

AbstractThis study aimed to determine the effectiveness and safety of varenicline versus NRT for smoking cessation in people with neurodevelopmental disorders, compared to those without, at up to four years after exposure. We analysed electronic medical records from the Clinical Practice Research Datalink using three different statistical approaches: multivariable logistic regression, propensity score matching (PSM), and instrumental variable analysis. Exposure was prescription of varenicline versus NRT and the primary outcome was smoking cessation at 2-years. We included 235,314 people aged 18 and above with eligible smoking cessation prescriptions in the effectiveness analysis. Smokers with neurodevelopmental disorders were 48% less likely (95% confidence interval: 42%, 54%) to be prescribed varenicline than NRT, compared to smokers without neurodevelopmental disorders. At 2-year follow-up, smokers with neurodevelopmental disorders prescribed varenicline were 38% more likely to quit smoking (95% confidence interval: 6%, 78%). Similar results were obtained using PSM and instrumental variable analyses. There was little evidence showing that varenicline increased the likelihood of mental health related adverse events in people with neurodevelopmental disorders. Varenicline is less likely to be prescribed to people with neurodevelopmental disorders despite results suggesting it is more effective than NRT and little evidence of increased likelihood of mental health related adverse events.
A prospective compound screening contest identified broader inhibitors for Sirtuin 1
Authors: Chiba Shuntaro , Ohue Masahito , Gryniukova Anastasiia , Borysko Petro , Zozulya Sergey , Yasuo Nobuaki , Yoshino Ryunosuke , Ikeda Kazuyoshi , Shin Woong-Hee , Kihara Daisuke , Iwadate Mitsuo , Umeyama Hideaki , Ichikawa Takaaki , Teramoto Reiji , Hsin Kun-Yi , Gupta Vipul , Kitano Hiroaki , Sakamoto Mika , Higuchi Akiko , Miura Nobuaki , Yura Kei , Mochizuki Masahiro , Ramakrishnan Chandrasekaran , Thangakani A. Mary , Velmurugan D. , Gromiha M. Michael , Nakane Itsuo , Uchida Nanako , Hakariya Hayase , Tan Modong , Nakamura Hironori K. , Suzuki Shogo D. , Ito Tomoki , Kawatani Masahiro , Kudoh Kentaroh , Takashina Sakurako , Yamamoto Kazuki Z. , Moriwaki Yoshitaka , Oda Keita , Kobayashi Daisuke , Okuno Tatsuya , Minami Shintaro , Chikenji George , Prathipati Philip , Nagao Chioko , Mohsen Attayeb , Ito Mari , Mizuguchi Kenji , Honma Teruki , Ishida Takashi , Hirokawa Takatsugu , Akiyama Yutaka , Sekijima Masakazu 
Published: December 2019

AbstractPotential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds usingin silicomethods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified.
Preventive Pharmacotherapy for Cardiovascular Disease: A Modelling Study Considering Health Gain, Costs, and Cost-Effectiveness when Stratifying by Absolute Risk
Authors: Nghiem Nhung , Knight Josh , Mizdrak Anja , Blakely Tony , Wilson Nick 
Published: December 2019

AbstractCardiovascular disease (CVD) is the leading cause of death internationally. We aimed to model the impact of CVD preventive double therapy (a statin and anti-hypertensive) by clinician-assessed absolute risk level. An established and validated multi-state life-table model for the national New Zealand (NZ) population was adapted. The new version of the model specifically considered the 60–64-year-old male population which was stratified by risk using a published NZ-specific CVD risk equation. The intervention period of treatment was for five years, but a lifetime horizon was used for measuring benefits and costs (a five-year horizon was also implemented). We found that for this group offering double therapy was highly cost-effective in all absolute risk categories (eg, NZ$1580 per QALY gained in the >20% in 5 years risk stratum; 95%UI: Dominant to NZ$3990). Even in the lowest risk stratum (≤5% risk in 5 years), the cost per QALY was only NZ$25,500 (NZ$28,200 and US$19,100 in 2018). At an individual level, the gain for those who responded to the screening offer and commenced preventive treatment ranged from 0.6 to 4.9 months of quality-adjusted life gained (or less than a month gain with a five-year horizon). Nevertheless, at the individual level, patient considerations are critical as some people may decide that this amount of average health gain does not justify taking daily medication.
Resistance to Haemonchus contortus in Corriedale sheep is associated to high parasite-specific IgA titer and a systemic Th2 immune response
Authors: Escribano Cecilia , Saravia Anderson , Costa Monique , Castells Daniel , Ciappesoni Gabriel , Riet-Correa Franklin , Freire Teresa 
Published: December 2019

AbstractGastrointestinal nematode infections, including Haemonchus contortus, are one of the main causes of economic losses to ovine farmers worldwide. In order to contribute to the control of nematode infections and avoid parasite spreading we generated divergent resistant and susceptible sheep breeds and evaluated the adaptive immunity of these animals developed upon experimental infection against H. contortus. The selection of resistant or susceptible animals from the Corriedale Breed has been based on Expected Progeny Differences for faecal egg counts per gram. Furthermore, animals from the resistant Corriedale line were inseminated with imported semen from Australian Rylington Merino rams. Thus, the objective of this work was to analyze the adaptive immune response in both susceptible and resistant obtained lambs. Our results indicate that there is a potent parasite-specific local and systemic immune response in resistant animals and that although susceptible lambs can produce high levels of IgA antibodies during the infection, their antibody response is delayed which, together with an impaired specific-Th2 response, does not contribute to initial parasite elimination. Our results shed light into the immune mechanisms that mediate resistance to H. contortus and could constitute important assets to sheep farmers, not only as a means to detect resistance, but also to enhance the efficiency of selection in stud flocks.