bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the Consistency of ECMWF Ensemble Forecasts
Authors: Richardson David S. , Cloke Hannah L. , Pappenberger Florian 
Published: May 2020

AbstractAn expected benefit of ensemble forecasts is that a sequence of consecutive forecasts valid for the same time will be more consistent than an equivalent sequence of individual forecasts. Inconsistent (jumpy) forecasts can cause users to lose confidence in the forecasting system. We present a first systematic, objective evaluation of the consistency of the European Centre for Medium‐Range Weather Forecasts (ECMWF) ensemble using a measure of forecast divergence that takes account of the full ensemble distribution. Focusing on forecasts of the North Atlantic Oscillation and European Blocking regimes up to 2 weeks ahead, we identify occasional large inconsistency between successive runs, with the largest jumps tending to occur at 7–9 days lead. However, care is needed in the interpretation of ensemble jumpiness. An apparent clear flip‐flop in a single index may hide a more complex predictability issue which may be better understood by examining the ensemble evolution in phase space.
Impact of HPV vaccination on cervical screening performance: a population-based cohort study
Authors: Lei Jiayao , Ploner Alexander , Lehtinen Matti , Sparén Pär , Dillner Joakim , Elfström K. Miriam 
Published: May 2020

Abstract
Background
Human papillomavirus (HPV) vaccination is predicted to lower the positive predictive value (PPV) of cytology.

Methods
We included 153,250 girls born between 1989 and 1993, resident in Sweden since the introduction of HPV vaccines (October 2006) and attending cervical screening at age 23 years. We assessed their first cytology and following histopathological diagnosis using Swedish National Cervical Screening Registry (NKCx). By linkage with the national Swedish HPV vaccination registry, we determined PPV of abnormal cytology for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and the differences with 95% confidence intervals (CIs) according to vaccination status.

Results
The PPV of high-grade cytology for CIN2+ was 69.9% (95% CI, 67.9–71.9), 64.9% (95% CI, 59.8–69.8) and 57.4% (95% CI, 50.9–63.7) among women unvaccinated, initiating vaccination at age 17–22 years and initiating vaccination before age 17 years, corresponding to reduction in PPV by 8% (95% CI, 0–15%) and 17% (95% CI, 7–26%) in vaccinated groups after adjustment for birth cohort, respectively.

Conclusion
The PPV of cytology for CIN2+ decreased among vaccinated women, and the decrease was stronger for girls vaccinated at younger ages. A switch from cytology to HPV testing might potentially improve the screening performance.
Integrated single-cell and bulk gene expression and ATAC-seq reveals heterogeneity and early changes in pathways associated with resistance to cetuximab in HNSCC-sensitive cell lines
Authors: Kagohara Luciane T. , Zamuner Fernando , Davis-Marcisak Emily F. , Sharma Gaurav , Considine Michael , Allen Jawara , Yegnasubramanian Srinivasan , Gaykalova Daria A. , Fertig Elana J. 
Published: May 2020

Abstract
Background
Identifying potential resistance mechanisms while tumour cells still respond to therapy is critical to delay acquired resistance.

Methods
We generated the first comprehensive multi-omics, bulk and single-cell data in sensitive head and neck squamous cell carcinoma (HNSCC) cells to identify immediate responses to cetuximab. Two pathways potentially associated with resistance were focus of the study: regulation of receptor tyrosine kinases by TFAP2A transcription factor, and epithelial-to-mesenchymal transition (EMT).

Results
Single-cell RNA-seq demonstrates heterogeneity, with cell-specific TFAP2A and VIM expression profiles in response to treatment and also with global changes to various signalling pathways. RNA-seq and ATAC-seq reveal global changes within 5 days of therapy, suggesting early onset of mechanisms of resistance; and corroborates cell line heterogeneity, with different TFAP2A targets or EMT markers affected by therapy. Lack of TFAP2A expression is associated with HNSCC decreased growth, with cetuximab and JQ1 increasing the inhibitory effect. Regarding the EMT process, short-term cetuximab therapy has the strongest effect on inhibiting migration. TFAP2A silencing does not affect cell migration, supporting an independent role for both mechanisms in resistance.

Conclusion
Overall, we show that immediate adaptive transcriptional and epigenetic changes induced by cetuximab are heterogeneous and cell type dependent; and independent mechanisms of resistance arise while tumour cells are still sensitive to therapy.
MCL-1Matrix maintains neuronal survival by enhancing mitochondrial integrity and bioenergetic capacity under stress conditions
Authors: Anilkumar Ujval , Khacho Mireille , Cuillerier Alexanne , Harris Richard , Patten David A. , Bilen Maria , Iqbal Mohamed Ariff , Guo Ding Yuan , Trudeau Louis-Eric , Park David S. , Harper Mary-Ellen , Burelle Yan , Slack Ruth S. 
Published: May 2020

AbstractMitochondria play a crucial role in neuronal survival through efficient energy metabolism. In pathological conditions, mitochondrial stress leads to neuronal death, which is regulated by the anti-apoptotic BCL-2 family of proteins. MCL-1 is an anti-apoptotic BCL-2 protein localized to mitochondria either in the outer membrane (OM) or inner membrane (Matrix), which have distinct roles in inhibiting apoptosis and promoting bioenergetics, respectively. While the anti-apoptotic role for Mcl1 is well characterized, the protective function of MCL-1 Matrix remains poorly understood. Here, we show MCL-1OM and MCL-1Matrix prevent neuronal death through distinct mechanisms. We report that MCL-1Matrix functions to preserve mitochondrial energy transduction and improves respiratory chain capacity by modulating mitochondrial oxygen consumption in response to mitochondrial stress. We show that MCL-1Matrix protects neurons from stress by enhancing respiratory function, and by inhibiting mitochondrial permeability transition pore opening. Taken together, our results provide novel insight into how MCL-1Matrix may confer neuroprotection under stress conditions involving loss of mitochondrial function.
Dual targeting of BCL2 and MCL1 rescues myeloma cells resistant to BCL2 and MCL1 inhibitors associated with the formation of BAX/BAK hetero-complexes
Authors: Seiller Carolane , Maiga Sophie , Touzeau Cyrille , Bellanger Céline , Kervoëlen Charlotte , Descamps Géraldine , Maillet Laurent , Moreau Philippe , Pellat-Deceunynck Catherine , Gomez-Bougie Patricia , Amiot Martine 
Published: May 2020

AbstractMultiple myeloma is a plasma cell malignancy that escapes from apoptosis by heterogeneously over-expressing anti-apoptotic BCL2 proteins. Myeloma cells with a t(11;14) translocation present a particular vulnerability to BCL2 inhibition while a majority of myeloma cells relies on MCL1 for survival. The present study aimed to determine whether the combination of BCL2 and MCL1 inhibitors at low doses could be of benefit for myeloma cells beyond the single selective inhibition of BCL2 or MCL1. We identified that half of patients were not efficiently targeted neither by BCL2 inhibitor nor MCL1 inhibitor. Seventy percent of these myeloma samples, either from patients at diagnosis or relapse, presented a marked increase of apoptosis upon low dose combination of both inhibitors. Interestingly, primary cells from a patient in progression under venetoclax treatment were not sensitive ex vivo to neither venetoclax nor to MCL1 inhibitor, whereas the combination of both efficiently induced cell death. This finding suggests that the combination could overcome venetoclax resistance. The efficacy of the combination was also confirmed in U266 xenograft model resistant to BCL2 and MCL1 inhibitors. Mechanistically, we demonstrated that the combination of both inhibitors favors apoptosis in a BAX/BAK dependent manner. We showed that activated BAX was readily increased upon the inhibitor combination leading to the formation of BAK/BAX hetero-complexes. We found that BCLXL remains a major resistant factor of cell death induced by this combination. The present study supports a rational for the clinical use of venetoclax/S63845 combination in myeloma patients with the potential to elicit significant clinical activity when both single inhibitors would not be effective but also to overcome developed in vivo venetoclax resistance.
Building and identifying highly active oxygenated groups in carbon materials for oxygen reduction to H2O2
Authors: Han Gao-Feng , Li Feng , Zou Wei , Karamad Mohammadreza , Jeon Jong-Pil , Kim Seong-Wook , Kim Seok-Jin , Bu Yunfei , Fu Zhengping , Lu Yalin , Siahrostami Samira , Baek Jong-Beom 
Published: May 2020

AbstractThe one-step electrochemical synthesis of H2O2 is an on-site method that reduces dependence on the energy-intensive anthraquinone process. Oxidized carbon materials have proven to be promising catalysts due to their low cost and facile synthetic procedures. However, the nature of the active sites is still controversial, and direct experimental evidence is presently lacking. Here, we activate a carbon material with dangling edge sites and then decorate them with targeted functional groups. We show that quinone-enriched samples exhibit high selectivity and activity with a H2O2 yield ratio of up to 97.8 % at 0.75 V vs. RHE. Using density functional theory calculations, we identify the activity trends of different possible quinone functional groups in the edge and basal plane of the carbon nanostructure and determine the most active motif. Our findings provide guidelines for designing carbon-based catalysts, which have simultaneous high selectivity and activity for H2O2 synthesis.
Demographic and genetic factors influence the abundance of infiltrating immune cells in human tissues
Authors: Marderstein Andrew R. , Uppal Manik , Verma Akanksha , Bhinder Bhavneet , Tayyebi Zakieh , Mezey Jason , Clark Andrew G. , Elemento Olivier 
Published: May 2020

AbstractDespite infiltrating immune cells having an essential function in human disease and patients’ responses to treatments, mechanisms influencing variability in infiltration patterns remain unclear. Here, using bulk RNA-seq data from 46 tissues in the Genotype-Tissue Expression project, we apply cell-type deconvolution algorithms to evaluate the immune landscape across the healthy human body. We discover that 49 of 189 infiltration-related phenotypes are associated with either age or sex (FDR < 0.1). Genetic analyses further show that 31 infiltration-related phenotypes have genome-wide significant associations (iQTLs) (P < 5.0 × 10−8), with a significant enrichment of same-tissue expression quantitative trait loci in suggested iQTLs (P < 10−5). Furthermore, we find an association between helper T cell content in thyroid tissue and aCOMMD3/DNAJC1regulatory variant (P = 7.5 × 10−10), which is associated with thyroiditis in other cohorts. Together, our results identify key factors influencing inter-individual variability of immune infiltration, to provide insights on potential therapeutic targets.
Nanoengineering room temperature ferroelectricity into orthorhombic SmMnO3 films
Authors: Choi Eun-Mi , Maity Tuhin , Kursumovic Ahmed , Lu Ping , Bi Zenxhing , Yu Shukai , Park Yoonsang , Zhu Bonan , Wu Rui , Gopalan Venkatraman , Wang Haiyan , MacManus-Driscoll Judith L. 
Published: May 2020

AbstractOrthorhombic RMnO3 (R = rare-earth cation) compounds are type-II multiferroics induced by inversion-symmetry-breaking of spin order. They hold promise for magneto-electric devices. However, no spontaneous room-temperature ferroic property has been observed to date in orthorhombic RMnO3. Here, using 3D straining in nanocomposite films of (SmMnO3)0.5((Bi,Sm)2O3)0.5, we demonstrate room temperature ferroelectricity and ferromagnetism with TC,FM ~ 90 K, matching exactly with theoretical predictions for the induced strain levels. Large in-plane compressive and out-of-plane tensile strains (−3.6% and +4.9%, respectively) were induced by the stiff (Bi,Sm)2O3 nanopillars embedded. The room temperature electric polarization is comparable to other spin-driven ferroelectric RMnO3 films. Also, while bulk SmMnO3 is antiferromagnetic, ferromagnetism was induced in the composite films. The Mn-O bond angles and lengths determined from density functional theory explain the origin of the ferroelectricity, i.e. modification of the exchange coupling. Our structural tuning method gives a route to designing multiferroics.
Clinical utility of 24-h rapid trio-exome sequencing for critically ill infants
Authors: Wang Huijun , Qian Yanyan , Lu Yulan , Qin Qian , Lu Guoping , Cheng Guoqiang , Zhang Ping , Yang Lin , Wu Bingbing , Zhou Wenhao 
Published: May 2020

AbstractGenetic diseases are a leading cause of death in infants in the intensive care setting; therefore, rapid and accurate genetic diagnosis is desired. To validate 24-h trio-exome sequencing (TES), samples from probands and their parents were processed by the AmpliSeq /Ion S5XL platform in a hospital clinical laboratory. Infants from the intensive care unit (ICU) suspected of having a genetic disease were enrolled. Regular and 24-h TES using the Agilent SureSelect capture kit/Illumina platform were performed on all samples in parallel. Of 33 enrolled infants, 23 received positive results with rapid TES, and an additional two diagnoses were achieved with regular TES. Among the 23 diagnosed patients, 10 experienced changes in medical management, such as hematopoietic stem cell transplant. Ten diagnosed cases were discharged prior to receiving the regular TES results; six received timely symptom control, and four withdrew medical support. Rapid TES enabled faster time to diagnosis, which resulted in an overall decrease in length of hospital stay. The 24-h TES can serve as a rapid response tool for patients with suspected monogenic disorders and can guide clinical decision-making in urgent cases.
A systematic review and meta-analysis of bone loss in space travelers
Authors: Stavnichuk Mariya , Mikolajewicz Nicholas , Corlett Tatsuya , Morris Martin , Komarova Svetlana V. 
Published: May 2020

AbstractBone loss in space travelers is a major challenge for long-duration space exploration. To quantify microgravity-induced bone loss in humans, we performed a meta-analysis of studies systematically identified from searching Medline, Embase, Web of Science, BIOSIS, NASA Technical reports, and HathiTrust, with the last update in November 2019. From 25 articles selected to minimize the overlap between reported populations, we extracted post-flight bone density values for 148 individuals, and in-flight and post-flight biochemical bone marker values for 124 individuals. A percentage difference in bone density relative to pre-flight was positive in the skull, +2.2% [95% confidence interval: +1.1, +3.3]; neutral in the thorax/upper limbs, −0.7% [−1.3, −0.2]; and negative in the lumbar spine/pelvis, −6.2 [−6.7, −5.6], and lower limbs, −5.4% [−6.0, −4.9]. In the lower limb region, the rate of bone loss was −0.8% [−1.1, −0.5] per month. Bone resorption markers increased hyperbolically with a time to half-max of 11 days [9, 13] and plateaued at 113% [108, 117] above pre-flight levels. Bone formation markers remained unchanged during the first 30 days and increased thereafter at 7% [5, 10] per month. Upon landing, resorption markers decreased to pre-flight levels at an exponential rate that was faster after longer flights, while formation markers increased linearly at 84% [39, 129] per month for 3–5 months post-flight. Microgravity-induced bone changes depend on the skeletal-site position relative to the gravitational vector. Post-flight recovery depends on spaceflight duration and is limited to a short post-flight period during which bone formation exceeds resorption.
Sources of seasonal wetland methane emissions in permafrost regions of the Qinghai-Tibet Plateau
Authors: Zhang Shunyao , Zhang Fugui , Shi Zeming , Qin Aihua , Wang Huiyan , Sun Zhongjun , Yang Zhibin , Zhu Youhai , Pang Shouji , Wang Pingkang 
Published: May 2020

AbstractIn this study, systematic soil methane cycle geochemical monitoring was carried out in a typical gas hydrate region in the Qinghai-Tibet Plateau. Soil gas samples were collected for hydrocarbon components and carbon isotope analysis. Meanwhile, soil-methane fluxes from the upper active layer (20–30 cm) were monitored during six months of one year. The results of this research provide evidence of a new source of methane emission from wetland soils in permafrost regions: gas hydrate release. Sites with large methane emissions were found using flux monitoring, the characteristics of thermogenic methane were identified using carbon isotope tracing, and the relationship between emission by soils and effusion from gas hydrates was determined through correlation analyses of soil-adsorbed hydrocarbons. Seasonal variation of methane emissions are also discussed by considering the emission of bacterial methane, thermogenic methane, and the absorption of methane from the soil active layer. These comprehensive findings provide valuable information for carbon cycle research of wetlands in permafrost regions.
Factors governing outbreak dynamics in a forest intensively managed for mountain pine beetle
Authors: Kunegel-Lion Mélodie , Lewis Mark A. 
Published: May 2020

AbstractMountain pine beetle (MPB) outbreaks have caused major economic losses and ecological consequences in North American pine forests. Ecological and environmental factors impacting MPB life-history and stands susceptibility can help with the detection of MPB infested trees and thereby, improve control. Temperatures, water stress, host characteristics, and beetle pressure are among those ecological and environmental factors. They play different roles on MPB population dynamics at the various stages of an outbreak and these roles can be affected by intensive management. However, to make detailed connections between ecological and environmental variables and MPB outbreak phases, a deeper quantitative analysis on local scales is needed. Here, we used logistic regressions on a highly-detailed and georeferenced data set to determine the factors driving MPB infestations for the different phases of the current isolated MPB outbreak in Cypress Hills. While we showed that the roles of ecological and environmental factors in a forest intensively controlled for MPB are consistent with the literature for uncontrolled forests, we determined how these factors shifted through onset, peak, and collapse phases of the intensively controlled forest. MPB presence mostly depends on nearby beetle pressure, notably for the outbreak peak. However additional weather and host variables are necessary to achieve high predictive ability for MPB outbreak locations. Our results can help managers make appropriate decisions on where and how to focus their effort, depending on which phase the outbreak is in.
Characterization of a novel automated microfiltration device for the efficient isolation and analysis of circulating tumor cells from clinical blood samples
Authors: Yee-de León Juan F. , Soto-García Brenda , Aráiz-Hernández Diana , Delgado-Balderas Jesús Rolando , Esparza Miguel , Aguilar-Avelar Carlos , Wong-Campos J. D. , Chacón Franco , López-Hernández José Y. , González-Treviño A. Mauricio , Yee-de León José R. , Zamora-Mendoza Jorge L. , Alvarez Mario M. , Trujillo-de Santiago Grissel , Gómez-Guerra Lauro S. , Sánchez-Domínguez Celia N. , Velarde-Calvillo Liza P. , Abarca-Blanco Alejandro 
Published: May 2020

AbstractThe detection and analysis of circulating tumor cells (CTCs) may enable a broad range of cancer-related applications, including the identification of acquired drug resistance during treatments. However, the non-scalable fabrication, prolonged sample processing times, and the lack of automation, associated with most of the technologies developed to isolate these rare cells, have impeded their transition into the clinical practice. This work describes a novel membrane-based microfiltration device comprised of a fully automated sample processing unit and a machine-vision-enabled imaging system that allows the efficient isolation and rapid analysis of CTCs from blood. The device performance was characterized using four prostate cancer cell lines, including PC-3, VCaP, DU-145, and LNCaP, obtaining high assay reproducibility and capture efficiencies greater than 93% after processing 7.5 mL blood samples spiked with 100 cancer cells. Cancer cells remained viable after filtration due to the minimal shear stress exerted over cells during the procedure, while the identification of cancer cells by immunostaining was not affected by the number of non-specific events captured on the membrane. We were also able to identify the androgen receptor (AR) point mutation T878A from 7.5 mL blood samples spiked with 50 LNCaP cells using RT-PCR and Sanger sequencing. Finally, CTCs were detected in 8 out of 8 samples from patients diagnosed with metastatic prostate cancer (mean ± SEM = 21 ± 2.957 CTCs/mL, median = 21 CTCs/mL), demonstrating the potential clinical utility of this device.
Video-call based newborn triage system for local birth centres can be established without major instalment costs using commercially available smartphones
Authors: Okada Junichiro , Hisano Tadashi , Unno Mitsuaki , Tanaka Yukari , Saikusa Mamoru , Kinoshita Masahiro , Harada Eimei , Iwata Sachiko , Iwata Osuke 
Published: May 2020

AbstractNeonates often develop transition problems after low-risk birth, precise assessment of which is difficult at primary birth centres. The aim of this study was to assess whether a video triage system can be established without a specially designed communication system between local birth centres and a tertiary neonatal intensive care unit in a region with a population of 700,000. 761 neonates who were referred to a tertiary neonatal intensive care unit were examined. During period 1 (April 2011-August 2015), only a voice call was available for consultations, whereas, during period 2 (September 2015-December 2017), a video call was additionally available. The respiratory condition was assessed based on an established visual assessment tool. A video consultation system was established by connecting personal smartphones at local birth centres with a host computer at a tertiary neonatal intensive care centre. During period 2, video-based triage was performed for 42.4% of 236 consultations at 30 birth centres. Sensitivity and specificity for predicting newborns with critical respiratory dysfunction changed from 0.758 to 0.898 and 0.684 to 0.661, respectively. A video consultation system for ill neonates was established without major instalment costs. Our strategy might improve the transportation system in both high- and low-resource settings.