bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of intravenous golimumab on health-related quality of life and work productivity in patients with active psoriatic arthritis: results of the Phase 3 GO-VIBRANT trial
Authors: Ogdie Alexis , Walsh Jessica A. , Chakravarty Soumya D. , Peterson Steven , Lo Kim Hung , Kim Lilianne , Li Nan , Hsia Elizabeth C. , Chan Eric K. H. , Kavanaugh Arthur , Husni M. Elaine
Published: March 2021

Introduction/objectives

To evaluate changes in health-related quality of life (HRQoL) and productivity following treatment with intravenous (IV) golimumab in patients with psoriatic arthritis (PsA).

Methods

Patients were randomized to IV golimumab 2 mg/kg (n=241) at Weeks 0, 4, then every 8 weeks (q8w) through Week 52 or placebo (n=239) at Weeks 0, 4, then q8w, with crossover to IV golimumab 2 mg/kg at Weeks 24, 28, then q8w through Week 52. Change from baseline in EuroQol-5 dimension-5 level (EQ-5D-5L) index and visual analog scale (EQ-VAS), daily productivity VAS, and the Work Limitations Questionnaire (WLQ) was assessed. Relationships between these outcomes and disease activity and patient functional capability were evaluated post hoc.

Results

At Week 8, change from baseline in EQ-5D-5L index (0.14 vs 0.04), EQ-VAS (17.16 vs 3.69), daily productivity VAS (−2.91 vs −0.71), and WLQ productivity loss score (−2.92 vs −0.78) was greater in the golimumab group versus the placebo group, respectively. At Week 52, change from baseline was similar in the golimumab and placebo-crossover groups (EQ-5D-5L index: 0.17 and 0.15; EQ-VAS: 21.61 and 20.84; daily productivity VAS: −2.89 and −3.31; WLQ productivity loss: −4.49 and −3.28, respectively). HRQoL and productivity were generally associated with disease activity and functional capability, with continued association from Week 8 through Week 52.

Conclusion

IV golimumab resulted in early and sustained improvements in HRQoL and productivity from Week 8 through 1 year in patients with PsA. HRQoL and productivity improvements were associated with improvements in disease activity and patient functional capability.

Key Points• In patients with active psoriatic arthritis (PsA), intravenous (IV) golimumab improved health-related quality of life (HRQoL) and productivity as early as 8 weeks and maintained improvement through 1 year• Improvements in HRQoL and productivity outcomes in patients with PsA treated with IV golimumab were associated with improvements in disease activity and patient functional capability outcomes• IV golimumab is an effective treatment option for PsA that can mitigate the negative effects of the disease on HRQoL and productivity
Demand-side decarbonization and electrification: EMF 35 JMIP study
Authors: Sakamoto Shogo , Nagai Yu , Sugiyama Masahiro , Fujimori Shinichiro , Kato Etsushi , Komiyama Ryoichi , Matsuo Yuhji , Oshiro Ken , Silva Herran Diego
Published: March 2021

Japan’s long-term strategy submitted to the United Nations Framework Convention on Climate Change emphasizes the importance of improving the electrification rates to reducing GHG emissions. Using the five models participating in Energy Modeling Forum 35 Japan Model Intercomparison project (JMIP), we focused on the demand-side decarbonization and analyzed the final energy composition required to achieve 80% reductions in GHGs by 2050 in Japan. The model results show that the electricity share in final energy use (electrification rate) needs to reach 37–66% in 2050 (26% in 2010) to achieve the emissions reduction of 80%. The electrification rate increases mainly due to switching from fossil fuel end-use technologies (i.e. oil water heater, oil stove and combustion-engine vehicles) to electricity end-use technologies (i.e. heat pump water heater and electric vehicles). The electricity consumption in 2050 other than AIM/Hub ranged between 840 and 1260 TWh (AIM/Hub: 1950TWh), which is comparable to the level seen in the last 10 years (950–1035 TWh). The pace at which electrification rate must be increased is a challenge. The model results suggest to increase the electrification pace to 0.46–1.58%/yr from 2030 to 2050. Neither the past electrification pace (0.30%/year from 1990 to 2010) nor the outlook of the Ministry of Economy, Trade and Industry (0.15%/year from 2010 to 2030) is enough to reach the suggested electrification rates in 2050. Therefore, more concrete measures to accelerate dissemination of electricity end-use technologies across all sectors need to be established.
Metamodeling of the Electrical Conditions in Submerged Arc Furnaces
Authors: Sparta Manuel , Varagnolo Damiano , Stråbø Kristian , Halvorsen Svenn Anton , Herland Egil Vålandsmyr , Martens Harald
Published: March 2021

Physics-based Finite Element Methods models can be used to investigate the electrical conditions in submerged arc furnaces (SAFs). However, their explicit solution may be very demanding in terms of time and computational resources. This makes these models difficult to employ during control operations and in fast prototyping. To obviate these inconveniences, we developed metamodels that are grounded on the physics-based model. In this context, a metamodel is a surrogate of an original model obtained using statistical analysis tools to determine approximate input–output relationships in a database of simulations from the original model. The metamodels for the SAF electrical conditions are shown to retain the same generalization capabilities as the original model while being computationally lightweight.
Design and Testing of an Underwater Microscope with Variable Objective Lens for the Study of Benthic Communities
Authors: Shahani Kamran , Song Hong , Mehdi Syed Raza , Sharma Awakash , Tunio Ghulam , Qureshi Junaidullah , Kalhoro Noor , Khaskheli Nooruddin
Published: March 2021

Monitoring the ecology and physiology of corals, sediments, planktons, and microplastic at a suitable spatial resolution is of great importance in oceanic scientific research. To meet this requirement, an underwater microscope with an electrically controlled variable lens was designed and tested. The captured microscopic images of corals, sediments, planktons, and microplastic revealed their physical, biological, and morphological characteristics. Further studies of the images also revealed the growth, degradation, and bleaching patterns of corals; the presence of plankton communities; and the types of microplastics. The imaging performance is majorly influenced by the choice of lenses, camera selection, and lighting method. Image dehazing, global saturation masks, and image histograms were used to extract the image features. Fundamental experimental proof was obtained with micro-scale images of corals, sediments, planktons, and microplastic at different magnifications. The designed underwater microscope can provide relevant new insights into the observation and detection of the future conditions of aquatic ecosystems.
Context-Aware Business Process Management
Authors: vom Brocke Jan , Baier Marie-Sophie , Schmiedel Theresa , Stelzl Katharina , Röglinger Maximilian , Wehking Charlotte
Published: March 2021

Context awareness is essential for successful business process management (BPM). So far, research has covered relevant BPM context factors and context-aware process design, but little is known about how to assess and select BPM methods in a context-aware manner. As BPM methods are involved in all stages of the BPM lifecycle, it is key to apply appropriate methods to efficiently use organizational resources. Following the design science paradigm, the study at hand addresses this gap by developing and evaluating the Context-Aware BPM Method Assessment and Selection (CAMAS) Method. This method assists method engineers in assessing in which contexts their BPM methods can be applied and method users in selecting appropriate BPM methods for given contexts. The findings of this study call for more context awareness in BPM method design and for a stronger focus on explorative BPM. They also provide insights into the status quo of existing BPM methods.
Vulnerability of groundwater to iron and manganese contamination in the coastal alluvial plain of a developing Indonesian city
Authors: Rusydi Anna Fadliah , Onodera Shin-Ichi , Saito Mitsuyo , Ioka Seiichiro , Maria Rizka , Ridwansyah Iwan , Delinom Robert M.
Published: March 2021

This paper evaluates environmental conditions responsible for the high concentrations of trace metals in Indonesian coastal groundwater. Indramayu, which has significant potential groundwater resources, but for which limited information is available regarding its vulnerability, is selected as our study area. Results show that Fe2+ and Mn2+ are natural contaminants in the groundwater of the study site. The correlations of trace metals with salinity and redox-sensitive parameters verify that saline water has a significant impact upon the dissolution of Fe and Mn. Furthermore, reductive condition is confirmed to be responsible for Fe and Mn dissolution with a less significant correlation compared to salinity. Moreover, the high concentrations of trace metals are coupled with high dissolved organic carbon (DOC), which indicates that reductive environment may arise because of organic-matter decomposition. Finally, the impact of human activity upon Fe and Mn dissolution is identified at the northern tip of Indramayu, where trace-metal contents are significantly elevated. Further, in the southern part, the groundwater condition is relatively more natural; thus, the impact of human activity upon the presence of Fe and Mn is lesser in this region.
DTFLOW: Inference and Visualization of Single-Cell Pseudotime Trajectory Using Diffusion Propagation
Authors: Wei Jiangyong , Zhou Tianshou , Zhang Xinan , Tian Tianhai
Published: March 2021

One of the major challenges in single-cell data analysis is the determination of cellular developmental trajectories using single-cell data. Although substantial studies have been conducted in recent years, more effective methods are still strongly needed to infer the developmental processes accurately. This work devises a new method, named DTFLOW, for determining the pseudo-temporal trajectories with multiple branches. DTFLOW consists of two major steps: a new method called Bhattacharyya kernel feature decomposition (BKFD) to reduce the data dimensions, and a novel approach named Reverse Searching on k-nearest neighbor graph (RSKG) to identify the multi-branching processes of cellular differentiation. In BKFD, we first establish a stationary distribution for each cell to represent the transition of cellular developmental states based on the random walk with restart algorithm, and then propose a new distance metric for calculating pseudotime of single cells by introducing the Bhattacharyya kernel matrix. The effectiveness of DTFLOW is rigorously examined by using four single-cell datasets. We compare the efficiency of DTFLOW with the published state-of-the-art methods. Simulation results suggest that DTFLOW has superior accuracy and strong robustness properties for constructing pseudotime trajectories. The Python source code of DTFLOW can be freely accessed at https://github.com/statway/DTFLOW.
Integrative Proteomic Analysis of Multiple Posttranslational Modifications in Inflammatory Response
Authors: Ji Feiyang , Zhou Menghao , Zhu Huihui , Jiang Zhengyi , Li Qirui , Ouyang Xiaoxi , Lv Yiming , Zhang Sainan , Wu Tian , Li Lanjuan
Published: March 2021

Posttranslational modifications (PTMs) of proteins, particularly acetylation, phosphorylation, and ubiquitination, play critical roles in the host innate immune response. PTMs’ dynamic changes and the crosstalk among them are complicated. To build a comprehensive dynamic network of inflammation-related proteins, we integrated data from the whole-cell proteome (WCP), acetylome, phosphoproteome, and ubiquitinome of human and mouse macrophages. Our datasets of acetylation, phosphorylation, and ubiquitination sites helped identify PTM crosstalk within and across proteins involved in the inflammatory response. Stimulation of macrophages by lipopolysaccharide (LPS) resulted in both degradative and non-degradative ubiquitination. Moreover, this study contributes to the interpretation of the roles of known inflammatory molecules and the discovery of novel inflammatory proteins.
Determinants of dietary diversity and its relationship with the nutritional status of pregnant women
Authors: Saaka Mahama , Mutaru Sofo , Osman Shaibu Mohammed
Published: March 2021

There is little information regarding factors that determine dietary diversity among pregnant women in Ghana. The present study, therefore, sought to assess the independent predictors of dietary diversity and its relationship with nutritional status of pregnant women in the Northern Region of Ghana. The present study was an analytical cross-sectional survey involving 423 pregnant women in different stages of gestation. The 24-h dietary recall method was used to assess minimum dietary diversity for women (MDD-W), and nutritional status was assessed using mid-upper arm circumference (MUAC) measurements. Binary logistic regression was performed to assess the association between maternal dietary diversity and maternal thinness and aPvalue of <0⋅05 was considered statistically significant. Of the 423 women, 79⋅9 % (95 % CI 76⋅1, 83⋅7) met the MDD-W and the prevalence of undernutrition among the pregnant women was 26⋅0 %. The analysis showed that women of low household wealth index were 48 % less likely (AOR 0⋅52, CI 0⋅31, 0⋅88) of meeting the MDD-W, whereas women from households of poor food insecurity were 88 % less likely (AOR 0⋅12, CI 0⋅05, 0⋅27) of achieving the MDD-W. Women of low household size were three times more likely of meeting the MDD-W (AOR 3⋅07, CI 1⋅13, 8⋅39). MDD-W was not associated with maternal underweight during pregnancy. In conclusion, the results of the present study showed that food insecurity and not low MDD-W, associated with mothers’ thinness (underweight) during pregnancy in peri-urban setting of Northern Ghana.
Generalized small cancellation conditions, non-positive curvature and diagrammatic reducibility
Authors: Blufstein Martín Axel , Minian Elías Gabriel , Sadofschi Costa Iván
Published: March 2021

We present a metric condition $\TTMetric$ which describes the geometry of classical small cancellation groups and applies also to other known classes of groups such as two-dimensional Artin groups. We prove that presentations satisfying condition $\TTMetric$ are diagrammatically reducible in the sense of Sieradski and Gersten. In particular, we deduce that the standard presentation of an Artin group is aspherical if and only if it is diagrammatically reducible. We show that, under some extra hypotheses, $\TTMetric$-groups have quadratic Dehn functions and solvable conjugacy problem. In the spirit of Greendlinger's lemma, we prove that if a presentation P = 〈X| R〉 of group G satisfies conditions $\TTMetric -C'(\frac {1}{2})$, the length of any nontrivial word in the free group generated by X representing the trivial element in G is at least that of the shortest relator. We also introduce a strict metric condition $\TTMetricStrict$, which implies hyperbolicity.
Humanoid NAO: A Kinematic Encounter
Authors: Sahu Chinmaya , Parhi Dayal R. , Kumar Priyadarshi Biplab , Muni Manoj Kumar , Chhotray Animesh , Pandey Krishna Kant
Published: March 2021

In the current research, kinematic analysis of a humanoid NAO is attempted. Here, both Denavit–Hartenberg (DH) parameter approach and multibody formulation approach have been analyzed. In the DH parameter approach, the NAO robot is solved by separating it into five individual kinematic chains. In the multibody formulation approach, NAO is divided into 15 segments, and each segment is analyzed. Kinematic analysis holds a significant importance; as from the data obtained in the kinematic analysis, the robots can be designed for real-time path planning and navigation. The current analysis is a novel approach to analyze the NAO based on its kinematic constraints.
Neuroprotective effects of Sonic hedgehog agonist SAG in a rat model of neonatal stroke
Authors: Nguyen Vien , Chavali Manideep , Larpthaveesarp Amara , Kodali Srikirti , Gonzalez Ginez , Franklin Robin J. M. , Rowitch David H. , Gonzalez Fernando
Published: March 2021

Background

Neonatal stroke affects 1 in 2800 live births and is a major cause of neurological injury. The Sonic hedgehog (Shh) signaling pathway is critical for central nervous system (CNS) development and has neuroprotective and reparative effects in different CNS injury models. Previous studies have demonstrated beneficial effects of small molecule Shh-Smoothened agonist (SAG) against neonatal cerebellar injury and it improves Down syndrome-related brain structural deficits in mice. Here we investigated SAG neuroprotection in rat models of neonatal ischemia–reperfusion (stroke) and adult focal white matter injury.

Methods

We used transient middle cerebral artery occlusion at P10 and ethidium bromide (EB) injection in adult rats to induce damage. Following surgery and SAG or vehicle treatment, we analyzed tissue loss, cell proliferation and fate, and behavioral outcome.

Results

We report that a single dose of SAG administered following neonatal stroke preserved brain volume, reduced gliosis, enhanced oligodendrocyte progenitor cell (OPC) and EC proliferation, and resulted in long-term cognitive improvement. Single-dose SAG also promoted proliferation of OPCs following focal demyelination in the adult rat.

Conclusions

These findings indicate benefit of one-time SAG treatment post insult in reducing brain injury and improving behavioral outcome after experimental neonatal stroke.

Impact

A one-time dose of small molecule Sonic hedgehog agonist protected against neonatal stroke and improved long-term behavioral outcomes in a rat model.

This study extends the use of Sonic hedgehog in treating developing brain injury, previously shown in animal models of Down syndrome and cerebellar injury.

Sonic hedgehog agonist is one of the most promising therapies in treating neonatal stroke thanks to its safety profile and low dosage.
Delivery mode and altered infant growth at 1 year of life in India
Authors: Babu Giridhara R. , Mueller Noel T. , Lewis Melissa Glenda , Krishnan Anjaly , Lobo Eunice , Deepa R. , Khetrapal Sonalini , Benjamin-Neelon Sara E.
Published: March 2021

Background

Cesarean section (C-section) delivered infants are more likely to be colonized by opportunistic pathogens, resulting in altered growth. We examined whether C-section (elective/emergency) vs vaginal delivery was associated with altered weight and linear growth at 1 year of life.

Methods

A total of 638 mother–infant pairs were included from MAASTHI cohort 2016–2019. Information on delivery mode was obtained from medical records. Based on WHO child growth standards, body mass index-forage z-score (BMI z) and length-for-age z-score (length z) were derived. We ran multivariable linear and Poisson regression models before and after multiple imputation.

Results

The rate of C-section was 43.4% (26.5%: emergency, 16.9%: elective). Percentage of infant overweight was 14.9%. Compared to vaginal delivery, elective C-section was associated with β = 0.57 (95% CI 0.20, 0.95) higher BMI z. Also infants born by elective C-section had RR = 2.44 (95% CI 1.35, 4.41) higher risk of being overweight; no such association was found for emergency C-section. Also, elective C-section delivery was associated with reduced linear growth at 1 year after multiple imputation (β = −0.38, 95% CI −0.76, −0.01).

Conclusions

Elective C-section delivery might contribute to excess weight and also possibly reduced linear growth at 1 year of age in children from low- and middle-income countries.

Impact

Our study, in a low-income setting, suggests that elective, but not emergency, C-section is associated with excess infant BMI z at 1 year of age and elective C (C-section) was also associated with altered linear growth but only in multiple imputation analyses.

Elective C-section was associated with a higher risk of being overweight at 1 year of age.

Our results indicate that decreasing medically unnecessary elective C-section deliveries may help limit excess weight gain and stunted linear growth among infants.
Depression, anxiety and associated factors among Chinese adolescents during the COVID-19 outbreak: a comparison of two cross-sectional studies
Authors: Chen Xu , Qi Han , Liu Rui , Feng Yuan , Li Wen , Xiang Mi , Cheung Teris , Jackson Todd , Wang Gang , Xiang Yu-Tao
Published: March 2021

The 2019 coronavirus disease (COVID-19) is a public health emergency of international concern. In China, all schools were shut down and students were home quarantined to prevent disease spread; these steps could have potential negative effects on mental health of adolescents. This study aimed to examine changes in depression and anxiety among Chinese adolescents during the COVID-19 epidemic, and explore factors associated with depression and anxiety. Two survey administrations were conducted among Chinese adolescents between February 20 and February 27 and between April 11 and April 19, 2020, respectively. The Center for Epidemiological Studies-Depression Scale (CES-D) and the 7-item Generalized Anxiety Disorder (GAD-7) scale were used to assess depressive symptoms and anxiety symptoms, respectively. A total of 9554 and 3886 adolescents participated in the first and second surveys. During the initial survey, the prevalence of depression was 36.6% (95% CI: 35.6–37.6%) while the prevalence of anxiety was 19% (95% CI: 18.2–19.8%). Rates of depression and anxiety increased to 57.0% (95% CI: 55.4–58.6%) and 36.7% (95% CI: 35.2–38.2%), respectively, in the second survey. Multivariable logistic regression analyses revealed that group membership in the second survey, female gender, senior secondary school enrollment, and concerns about entering a higher grade were positively associated with both depression and anxiety. Conversely, a sleep duration of ≥6 h/day, an exercise duration ≥30 min/day, having the same as typical or higher study efficiency during the COVID-19 outbreak, and living in provinces with 1000–9999 confirmed COVID-19 cases were negatively associated with depression and anxiety. In conclusion, compared to figures reported during the COVID-19 outbreak, the prevalence of depression and anxiety in Chinese adolescents significantly increased after the initial outbreak. Regular screening and appropriate interventions are urgently needed to reduce the risk for emotional disturbances among adolescents during and after the initial COVID-19 outbreaks.
A molecular switch in sulfur metabolism to reduce arsenic and enrich selenium in rice grain
Authors: Sun Sheng-Kai , Xu Xuejie , Tang Zhong , Tang Zhu , Huang Xin-Yuan , Wirtz Markus , Hell Rüdiger , Zhao Fang-Jie
Published: March 2021

Rice grains typically contain high levels of toxic arsenic but low levels of the essential micronutrient selenium. Anthropogenic arsenic contamination of paddy soils exacerbates arsenic toxicity in rice crops resulting in substantial yield losses. Here, we report the identification of the gain-of-function arsenite tolerant 1 (astol1) mutant of rice that benefits from enhanced sulfur and selenium assimilation, arsenic tolerance, and decreased arsenic accumulation in grains. The astol1 mutation promotes the physical interaction of the chloroplast-localized O-acetylserine (thiol) lyase protein with its interaction partner serine-acetyltransferase in the cysteine synthase complex. Activation of the serine-acetyltransferase in this complex promotes the uptake of sulfate and selenium and enhances the production of cysteine, glutathione, and phytochelatins, resulting in increased tolerance and decreased translocation of arsenic to grains. Our findings uncover the pivotal sensing-function of the cysteine synthase complex in plastids for optimizing stress resilience and grain quality by regulating a fundamental macronutrient assimilation pathway.
RNA m6A methylation orchestrates cancer growth and metastasis via macrophage reprogramming
Authors: Yin Huilong , Zhang Xiang , Yang Pengyuan , Zhang Xiaofang , Peng Yingran , Li Da , Yu Yanping , Wu Ye , Wang Yidi , Zhang Jinbao , Ding Xiaochen , Wang Xiangpeng , Yang Angang , Zhang Rui
Published: March 2021

N6-methyladenosine (m6A) is a reversible mRNA modification that has been shown to play important roles in various biological processes. However, the roles of m6A modification in macrophages are still unknown. Here, we discover that ablation of Mettl3 in myeloid cells promotes tumour growth and metastasis in vivo. In contrast to wild-type mice, Mettl3-deficient mice show increased M1/M2-like tumour-associated macrophage and regulatory T cell infiltration into tumours. m6A sequencing reveals that loss of METTL3 impairs the YTHDF1-mediated translation of SPRED2, which enhances the activation of NF-kB and STAT3 through the ERK pathway, leading to increased tumour growth and metastasis. Furthermore, the therapeutic efficacy of PD-1 checkpoint blockade is attenuated in Mettl3-deficient mice, identifying METTL3 as a potential therapeutic target for tumour immunotherapy.
Caldera resurgence during the 2018 eruption of Sierra Negra volcano, Galápagos Islands
Authors: Bell Andrew F. , La Femina Peter C. , Ruiz Mario , Amelung Falk , Bagnardi Marco , Bean Christopher J. , Bernard Benjamin , Ebinger Cynthia , Gleeson Matthew , Grannell James , Hernandez Stephen , Higgins Machel , Liorzou Céline , Lundgren Paul , Meier Nathan J. , Möllhoff Martin , Oliva Sarah-Jaye , Ruiz Andres Gorki , Stock Michael J.
Published: March 2021

Recent large basaltic eruptions began after only minor surface uplift and seismicity, and resulted in caldera subsidence. In contrast, some eruptions at Galápagos Island volcanoes are preceded by prolonged, large amplitude uplift and elevated seismicity. These systems also display long-term intra-caldera uplift, or resurgence. However, a scarcity of observations has obscured the mechanisms underpinning such behaviour. Here we combine a unique multiparametric dataset to show how the 2018 eruption of Sierra Negra contributed to caldera resurgence. Magma supply to a shallow reservoir drove 6.5 m of pre-eruptive uplift and seismicity over thirteen years, including an Mw5.4 earthquake that triggered the eruption. Although co-eruptive magma withdrawal resulted in 8.5 m of subsidence, net uplift of the inner-caldera on a trapdoor fault resulted in 1.5 m of permanent resurgence. These observations reveal the importance of intra-caldera faulting in affecting resurgence, and the mechanisms of eruption in the absence of well-developed rift systems.
Structure–function analysis of oncogenic EGFR Kinase Domain Duplication reveals insights into activation and a potential approach for therapeutic targeting
Authors: Du Zhenfang , Brown Benjamin P. , Kim Soyeon , Ferguson Donna , Pavlick Dean C. , Jayakumaran Gowtham , Benayed Ryma , Gallant Jean-Nicolas , Zhang Yun-Kai , Yan Yingjun , Red-Brewer Monica , Ali Siraj M. , Schrock Alexa B. , Zehir Ahmet , Ladanyi Marc , Smith Adam W. , Meiler Jens , Lovly Christine M.
Published: March 2021

Mechanistic understanding of oncogenic variants facilitates the development and optimization of treatment strategies. We recently identified in-frame, tandem duplication of EGFR exons 18 - 25, which causes EGFR Kinase Domain Duplication (EGFR-KDD). Here, we characterize the prevalence of ERBB family KDDs across multiple human cancers and evaluate the functional biochemistry of EGFR-KDD as it relates to pathogenesis and potential therapeutic intervention. We provide computational and experimental evidence that EGFR-KDD functions by forming asymmetric EGF-independent intra-molecular and EGF-dependent inter-molecular dimers. Time-resolved fluorescence microscopy and co-immunoprecipitation reveals EGFR-KDD can form ligand-dependent inter-molecular homo- and hetero-dimers/multimers. Furthermore, we show that inhibition of EGFR-KDD activity is maximally achieved by blocking both intra- and inter-molecular dimerization. Collectively, our findings define a previously unrecognized model of EGFR dimerization, providing important insights for the understanding of EGFR activation mechanisms and informing personalized treatment of patients with tumors harboring EGFR-KDD. Finally, we establish ERBB KDDs as recurrent oncogenic events in multiple cancers.
Trace element catalyses mineral replacement reactions and facilitates ore formation
Authors: Xing Yanlu , Brugger Joël , Etschmann Barbara , Tomkins Andrew G. , Frierdich Andrew J. , Fang Xiya
Published: March 2021

Reaction-induced porosity is a key factor enabling protracted fluid-rock interactions in the Earth’s crust, promoting large-scale mineralogical changes during diagenesis, metamorphism, and ore formation. Here, we show experimentally that the presence of trace amounts of dissolved cerium increases the porosity of hematite (Fe2O3) formed via fluid-induced, redox-independent replacement of magnetite (Fe3O4), thereby increasing the efficiency of coupled magnetite replacement, fluid flow, and element mass transfer. Cerium acts as a catalyst affecting the nucleation and growth of hematite by modifying the Fe2+(aq)/Fe3+(aq) ratio at the reaction interface. Our results demonstrate that trace elements can enhance fluid-mediated mineral replacement reactions, ultimately controlling the kinetics, texture, and composition of fluid-mineral systems. Applied to some of the world’s most valuable orebodies, these results provide new insights into how early formation of extensive magnetite alteration may have preconditioned these ore systems for later enhanced metal accumulation, contributing to their sizes and metal endowment.
Multi-omics analysis reveals contextual tumor suppressive and oncogenic gene modules within the acute hypoxic response
Authors: Andrysik Zdenek , Bender Heather , Galbraith Matthew D. , Espinosa Joaquin M.
Published: March 2021

Cellular adaptation to hypoxia is a hallmark of cancer, but the relative contribution of hypoxia-inducible factors (HIFs) versus other oxygen sensors to tumorigenesis is unclear. We employ a multi-omics pipeline including measurements of nascent RNA to characterize transcriptional changes upon acute hypoxia. We identify an immediate early transcriptional response that is strongly dependent on HIF1A and the kinase activity of its cofactor CDK8, includes indirect repression of MYC targets, and is highly conserved across cancer types. HIF1A drives this acute response via conserved high-occupancy enhancers. Genetic screen data indicates that, in normoxia, HIF1A displays strong cell-autonomous tumor suppressive effects through a gene module mediating mTOR inhibition. Conversely, in advanced malignancies, expression of a module of HIF1A targets involved in collagen remodeling is associated with poor prognosis across diverse cancer types. In this work, we provide a valuable resource for investigating context-dependent roles of HIF1A and its targets in cancer biology.
Computational modelling of nanotube delivery of anti-cancer drug into glutathione reductase enzyme
Authors: Begum Saheen Shehnaz , Das Dharitri , Gour Nand Kishor , Deka Ramesh Chandra
Published: March 2021

Density functional theory method combined with docking and molecular dynamics simulations are used to understand the interaction of carmustine with human glutathione reductase enzyme. The active site of the enzyme is evaluated by docking simulation is used for molecular dynamics simulation to deliver the carmustine molecule by (5,5) single walled carbon nanotube (SWCNT). Our model of carmustine in the active site of GR gives a negative binding energy that is further refined by QM/MM study in gas phase and solvent phase to confirm the stability of the drug molecule inside the active site. Once released from SWCNT, carmustine forms multiple polar and non-polar hydrogen bonding interactions with Tyr180, Phe209, Lys318, Ala319, Leu320, Leu321, Ile350, Thr352 and Val354 in the range of 2–4 Å. The SWCNT vehicle itself is held fix at its place due to multiple pi-pi stacking, pi-amide, pi-sigma interactions with the neighboring residues. These interactions in the range of 3–5 Å are crucial in holding the nanotube outside the drug binding region, hence, making an effective delivery. This study can be extended to envisage the potential applications of computational studies in the modification of known drugs to find newer targets and designing new and improved controlled drug delivery systems.
A study on the characteristics of cognitive function in patients with multiple system atrophy in China
Authors: Li Nannan , Yang Tianwen , Ran Weizheng , Zhang Xinning , Wang Yao , Xu Zhifang , Ren Shan , Zhao Qianyu , Guo Bingyu , Wang Sushi , Meng Fanxing , Chen Zhigang
Published: March 2021

Nonmotor symptoms in patients with multiple system atrophy (MSA) have received an increasing amount of attention in recent years, but no research on MSA patients' cognitive characteristics has been conducted in China. To evaluate the cognitive function of MSA patients in China. Using a case–control study design, 256 MSA patients and 64 controls were evaluated by the Montreal cognitive assessment (MoCA) scale to characterize their cognitive function. Like the controls, 60.5% of the patients with MSA had cognitive impairment, but the characteristics of cognitive impairment between the two groups were different. The cognitive impairment in MSA patients was prominent in the cognitive domains of visuospatial/executive functions, naming, attention, and orientation; particularly, the visuospatial/executive functions were the most significantly impaired, while impairment in language function was mainly seen in the controls. Besides, impairments in visuospatial/executive functions, attention, language, and orientation were more prominent in MSA-P (MSA with predominant Parkinsonism) patients than in MSA-C (MSA with predominant cerebellar ataxia). The cognitive impairments were more severe in patients with probable MSA than in patients with possible MSA. In addition, the results showed that the level of cognitive function was negatively correlated with the severity of MSA. This study, which characterized the cognitive function of MSA patients with the largest sample size known so far in China, found that patients with MSA do have cognitive impairment and display specific characteristics. Therefore, the cognitive impairment of MSA should be paid more attention.

The study has been registered in the Chinese Clinical Trial Registry (ChiCTR) (Registration No: ChiCTR1900022462).
Nanophotonic crystals on unpolished sapphire substrates for deep-UV light-emitting diodes
Authors: Tran Tinh Binh , AlQatari Feras , Luc Quang-Ho
Published: March 2021

A new method has been established and employed to create a random nanophotonic crystal (NPhC) structure without photolithography on the unpolished side of a single-side-polished sapphire substrate. This nano structure has potential use in enhancing the light-extraction efficiency (LEE) of deep ultraviolet light-emitting diodes (DUV-LEDs), and has never been built for DUV-LED applications before. Two mask layers in the nano scale (Au and SiO2) were used to create the NPhC and observed using scanning electron microscopy to have an average height of 400 nm and various sizes from 10 to 200 nm. Finally, a conventional DUV-LED and a DUV-LED device with NPhC were simulated using 2D Lumerical Finite-Difference Time-Domain (FDTD) for comparison. The results show that the LEE of the DUV-LED device with this NPhC integrated was significantly directly enhanced by up to 46% and 90% for TE and TM modes, respectively, compared to the conventional DUV-LED device. Thus, this NPhC is believed to be a new, key technique to enhance the LEE of DUV-LEDs.
Treatment of distal clavicle fracture of Neer type II with locking plate in combination with titanium cable under the guide
Authors: Wang Jun , Guan Jie , Liu Minbo , Cui Yongfeng , Zhang Yuhang
Published: March 2021

To observe and compare the curative effect of a locking plate plus titanium cable under the Guide device and clavicular hook plate in the treatment of Neer type II distal clavicle fractures. A prospective cohort study was conducted to analyse the clinical data of 36 patients with distal clavicle fractures from January 2016 to January 2019. The results were analysed. According to the random number method, the patients were divided into two groups: the titanium cable group (fixed with a titanium cable in combination with a locking plate) and hook plate group (fixed with a clavicular hook plate only). Under the guidance of a special device (for which a patent was obtained), in the titanium cable group, the coracoclavicular ligament was fixed with tension reduction, and then the distal clavicular fracture was fixed with a locking plate. In the hook plate group, the distal clavicle fracture was fixed with a hook plate. The incision length, operation time, bleeding volume and VAS score before, 1 week after and 1 year after the operation were compared between the two groups. The effect of the operation was evaluated by the Constant-Murley score before and 1 year after the operation. X-ray films were taken 2 days, 3 months, half a year and 1 year after the operation to observe the reduction and healing of fractures. At the same time, complications were recorded. The amount of bleeding was the same in the two groups. The operation time in the hook plate group was relatively short, and the difference was statistically significant (P < 0.05). The VAS score in the titanium cable group was significantly lower than that in the hook plate group one year after the operation. The Constant-Murley score in the titanium cable group and hook plate group was significantly higher 1 year after the operation. The number of postoperative complications in the titanium cable group was significantly lower than that in the hook plate group. The treatment of Neer type II distal clavicle fractures with a titanium cable plus a locking plate has a good curative effect, few complications and good postoperative recovery and thus is worth popularizing.
Immobilising hairpin DNA-conjugated distyryl boron dipyrromethene on gold@polydopamine core–shell nanorods for microRNA detection and microRNA-mediated photodynamic therapy
Authors: Dai Gaole , Choi Chun Kit K. , Zhou Yimin , Bai Qianqian , Xiao Yu , Yang Caixia , Choi Chung Hang Jonathan , Ng Dennis K. P.
Published: March 2021

A novel nanosystem based on polydopamine-coated gold nanorods has been designed and fabricated for detection of oncogenic microRNA-21 and microRNA-21-mediated photodynamic therapy.
A new synthetic protectin D1 analog 3-oxa-PD1n-3 DPA reduces neuropathic pain and chronic itch in mice
Authors: Nesman Jannicke Irina , Chen Ouyang , Luo Xin , Ji Ru-Rong , Serhan Charles N. , Hansen Trond Vidar
Published: March 2021

The novel protectin D1 analog 3-oxa-PD1n-3 DPA was synthesized. Nanogram amounts of this analog reduces neuropathic pain and chronic itch, and shows analgesic action in a mouse model of diabetic neuropathy.
Achieving high circularly polarized luminescence with push–pull helicenic systems: from rationalized design to top-emission CP-OLED applications
Authors: Dhbaibi Kais , Abella Laura , Meunier-Della-Gatta Sylvia , Roisnel Thierry , Vanthuyne Nicolas , Jamoussi Bassem , Pieters Grégory , Racine Benoît , Quesnel Etienne , Autschbach Jochen , Crassous Jeanne , Favereau Ludovic
Published: March 2021

A CPL intensity of up to 3 × 10−2 is achieved in π-extended 6-helicene derivatives, owing to an intense helicene-mediated exciton coupling. Corresponding top-emission CP-OLEDs afforded a promising gEl of around 8 × 10−3.
Formation of Ni(ii)-phenoxyl radical complexes by O2: a mechanistic insight into the reaction of Ni(ii)-phenol complexes with O2
Authors: Suzuki Takashi , Sato Akari , Oshita Hiromi , Yajima Tatsuo , Tani Fumito , Abe Hitoshi , Mieda-Higa Kaoru , Yanagisawa Sachiko , Ogura Takashi , Shimazaki Yuichi
Published: March 2021

The reaction of Ni(ii)-(phenol)(phenolate) complexes with O2 gave the Ni(ii)-phenoxyl radical complexes assisted by CH3OH. This reaction was concluded to undergo via the proton transfer–electron transfer type mechanism without redox of the Ni ion.
Spray-dried assembly of 3D N,P-Co-doped graphene microspheres embedded with core–shell CoP/MoP@C nanoparticles for enhanced lithium-ion storage
Authors: Muhammad Ishaq , Jabeen Maher , Wang Peiran , He Yu-Shi , Liao Xiao-Zhen , Ma Zi-Feng
Published: March 2021

A novel synthesis route was developed for the fabrication of 3D N,P dual-atom doped graphene (G-NP) microspheres embedded with core–shell CoP@C and MoP@C nanoparticles (CoP@C⊂G-NP and MoP@C⊂G-NP) as anode materials for lithium-ion batteries.
Crystal, electronic and magnetic structures of a novel series of intergrowth carbometalates R4Co2C3 (R = Y, Gd, Tb)
Authors: Levytskyi Volodymyr , Isnard Olivier , Kremer Reinhard K. , Babizhetskyy Volodymyr , Fontaine Bruno , Rocquefelte Xavier , Halet Jean-François , Gumeniuk Roman
Published: March 2021

R4Co2C3 (R = Gd, Tb) carbides are magnetic metals and their crystal structures result from the stacking of alternating RCoC (YCoC-type) and R2C (anti-CdCl2 type) fragments with a 2 : 1 ratio.
Fabrication of a porous NiFeP/Ni electrode for highly efficient hydrazine oxidation boosted H2 evolution
Authors: Wang Honglei , Tao Shengyang
Published: March 2021

Here, a simple dual-regulation strategy is reported to synthesize porous P-NiFeP/Ni nanoflowers for enabling the anodic hydrazine oxidation reaction and the cathodic energy-saving hydrogen evolution reaction.
Polymer defect engineering – conductive 2D organic platelets from precise thiophene-doped polyethylene
Authors: Suraeva Oksana , Jeong Beomjin , Asadi Kamal , Landfester Katharina , Wurm Frederik R. , Lieberwirth Ingo
Published: March 2021

Synthesis and crystallization of polyethylene with precisely positioned thiophene groups were used to produce polymer crystals with a conductive surface.
Correlating axial and equatorial ligand field effects to the single-molecule magnet performances of a family of dysprosium bis-methanediide complexes
Authors: Thomas-Hargreaves Lewis R. , Giansiracusa Marcus J. , Gregson Matthew , Zanda Emanuele , O'Donnell Felix , Wooles Ashley J. , Chilton Nicholas F. , Liddle Stephen T.
Published: March 2021

Studies on equatorial donor and CDyC angle variation effects on energy barriers to the slow relaxation of magnetisation are reported.
Machine learning dielectric screening for the simulation of excited state properties of molecules and materials
Authors: Dong Sijia S. , Govoni Marco , Galli Giulia
Published: March 2021

Machine learning can circumvent explicit calculation of dielectric response in first principles methods and accelerate simulations of optical properties of complex materials at finite temperature.
The ortho effect in directed C–H activation
Authors: Tóth Balázs L. , Monory Anna , Egyed Orsolya , Domján Attila , Bényei Attila , Szathury Bálint , Novák Zoltán , Stirling András
Published: March 2021

The term and concept of Ortho Effect (OE) is introduced for the description of steric effects in transition metal catalyzed directedorthoC–H activation reactions to explain and predict reactivities of substrates.
Evaluating the Language ENvironment Analysis System for Korean
Authors: McDonald Margarethe , Kwon Taeahn , Kim Hyunji , Lee Youngki , Ko Eon-Suk
Published: March 2021

Purpose

The algorithm of the Language ENvironment Analysis (LENA) system for calculating language environment measures was trained on American English; thus, its validity with other languages cannot be assumed. This article evaluates the accuracy of the LENA system applied to Korean.

Method

We sampled sixty 5-min recording clips involving 38 key children aged 7–18 months from a larger data set. We establish the identification error rate, precision, and recall of LENA classification compared to human coders. We then examine the correlation between standard LENA measures of adult word count, child vocalization count, and conversational turn count and human counts of the same measures.

Results

Our identification error rate (64% or 67%), including false alarm, confusion, and misses, was similar to the rate found in
Cristia, Lavechin, et al. (2020)
. The correlation between LENA and human counts for adult word count (
r
= .78 or .79) was similar to that found in the other studies, but the same measure for child vocalization count (
r
= .34–.47) was lower than the value in Cristia, Lavechin, et al., though it fell within ranges found in other non-European languages. The correlation between LENA and human conversational turn count was not high (
r
= .36–.47), similar to the findings in other studies.

Conclusions

LENA technology is similarly reliable for Korean language environments as it is for other non-English language environments. Factors affecting the accuracy of diarization include speakers' pitch, duration of utterances, age, and the presence of noise and electronic sounds.
Small‐signal‐based study of a two stage AC/DC and DC/DC battery charger using battery one time constant model
Authors: Hajisadeghian Hossein , Motie Birjandi Ali Akbar , Asadi Mehdi , Vazini Hossein
Published: March 2021

This study focuses on considering battery one time constant model in the design of controllers of a two‐stage AC/DC and DC/DC battery charger using the small‐signal approach. For this aim, small‐signal models of DC/DC and AC/DC converters and also the battery model are obtained. Moreover, the effect of disturbance terms are analysed to be omitted in controller loops. Simulation and experimental results of a 1 kW laboratory prototype show appropriate performance of designed controllers in tracking reference signals. Also, tuned controllers using this approach have guaranteed unity power factor and low total harmonic distortion. Furthermore, a complete charge cycle of a lithium‐ion battery evaluates the performance of the converter in different constant current/voltage controlling modes. In comparison with restive model consideration, results show a more accurate model with grater damping ration and better stability characteristics.