bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-speed railways and local economic performance: evidence from China’s prefecture-level cities
Authors: Li Chao , Zhao Zhao , Li Han 
Published: November 2021

Purpose
The purpose of this paper is to identify the causal effect of high-speed railways (HSRs) and investigate the affecting channels; the second purpose is to examine how HSRs change the distribution of economic activity across cities and sectors.

Design/methodology/approach
A difference-in-difference strategy is implemented to estimate the impact of recently built HSRs on local economic performance in China, exploiting the geography and time variations in HSR operations.

Findings
Using panel data from China’s City Statistical Yearbook 2001–2019, the authors find that HSRs lead to a significant increase in cities’ gross domestic product (GDP) and GDP per capita, but the authors do not find any significant change in GDP growth. This conclusion still holds true after the authors address the endogeneity problems. A mechanism analysis shows that HSRs improve local economic performance mainly by increasing fixed asset investment. The authors also find that the HSR investment is a policy that favors metropolitan areas due to the larger increase in the GDP for larger cities and with HSRs, the industrial and service sectors will further agglomerate in larger cities.

Originality/value
The authors contribute to the literature in several ways. First, this paper improves the estimation strategy in identifying the HSR impact on the local economic performance. Second, this paper investigates the affecting channels of HSRs. This paper proves that HSRs in China promote the cities’ economic performance mainly by increasing the fixed asset investment. Third, this study provides evidence for the new economic geography models pioneered by Krugman (1991).
Improving school performance and student academic orientation: the role of safety-oriented knowledge management and diversity
Authors: Birasnav M. , Gantasala Prabhakar Venugopal , Gantasala Swapna Bhargavi 
Published: November 2021

Purpose
The purpose of this study is to examine the influence of the implementation of safety-oriented knowledge management (KM) processes and student diversity acceptance in schools and the interaction effect of safety-oriented KM processes and student diversity acceptance over school performance and student academic orientation.

Design/methodology/approach
Responses of 977 American schools available in the database of the National Center for Education Statistics were analyzed using hierarchical regression analyses.

Findings
Results show that implementation of safety-oriented KM processes and diversity acceptance in schools have varying effects on school performance and student academic orientation. The impact of knowledge acquisition from parents on the academic achievement of students is positive and stronger in schools that are low in student diversity acceptance than schools that are high in student diversity acceptance.

Originality/value
This study adds value to the KM literature by exploring how KM processes are executed in American schools to improve their performance and students’ academic orientation and how diversity among students alters the strength of the relationships.
Immune activity in Merkel cell carcinoma
Authors: Nakamura Motoki , Morita Akimichi 
Published: November 2021

AbstractMerkel cell carcinoma (MCC) is widely known as a highly malignant skin cancer. The pathogenesis of MCC, however, remains mysterious due to the extremely small number of cases and its prevalence in the elderly. Despite its high‐grade malignancy, spontaneous regression occurs with some frequency. The immune activity of the tumor underlies this peculiar behavior. In recent years, immune checkpoint blockade therapies, including the anti‐programmed death ligand 1 antibody, have provided successful results. These therapies, however, are ineffective in approximately half the patients with advanced MCC and few treatments are available for those patients. In this review, we summarize the increasing body of evidence relating to the immune activity of MCC and immunological biomarkers. The interesting and sometimes peculiar behavior of MCC, such as their spontaneous regression, is largely due to their high immunosensitivity. Understanding the tumor immunokinetics of MCC should provide critical insight for understanding cancer immunotherapy. Here, we introduce a new classification for MCC according to its immune activity. Combined application of programmed death ligand 1 (a prognostic factor and predictor of the efficacy of immune checkpoint inhibitors in various cancers) with glucose‐6‐phosphate dehydrogenase (a new promising biomarker for MCC) may enable classification of MCC based on its immune status. Whether the new classification can be used to predict the efficacy of immune checkpoint blockade therapies remains to be evaluated in future studies, but the classification may facilitate future treatment selection.
The alternative sigma factors, rpoN1 and rpoN2 are required for mycophagous activity of Burkholderia gladioli strain NGJ1
Authors: Das Joyati , Kumar Rahul , Yadav Sunil Kumar , Jha Gopaljee 
Published: November 2021

SummaryBacteria utilize RpoN, an alternative sigma factor (σ54) to grow in diverse habitats, including nitrogen‐limiting conditions. Here, we report that a rice‐associated mycophagous bacterium Burkholderia gladioli strain NGJ1 encodes two paralogues of rpoN viz. rpoN1 and rpoN2. Both of them are upregulated during 24 h of mycophagous interaction with Rhizoctonia solani, a polyphagous fungal pathogen. Disruption of either one of rpoNs renders the mutant NGJ1 bacterium defective in mycophagy, whereas ectopic expression of respective rpoN genes restores mycophagy in the complementing strains. NGJ1 requires rpoN1 and rpoN2 for efficient biocontrol to prevent R. solani to establish disease in rice and tomato. Further, we have identified 17 genes having RpoN regulatory motif in NGJ1, majority of them encode potential type III secretion system (T3SS) effectors, nitrogen assimilation, and cellular transport‐related functions. Several of these RpoN regulated genes as well as certain previously reported T3SS apparatus (hrcC and hrcN) and effector (Bg_9562 and endo‐β‐1,3‐glucanase) encoding genes are upregulated in NGJ1 but not in ΔrpoN1 or ΔrpoN2 mutant bacterium, during mycophagous interaction with R. solani. This highlights that RpoN1 and RpoN2 modulate T3SS, nitrogen assimilation as well as cellular transport systems in NGJ1 and thereby promote bacterial mycophagy.
‘Candidatus Gromoviella agglomerans’, a novel intracellular Holosporaceae parasite of the ciliate Paramecium showing marked genome reduction
Authors: Castelli Michele , Lanzoni Olivia , Giovannini Michele , Lebedeva Natalia , Gammuto Leandro , Sassera Davide , Melekhin Maksim , Potekhin Alexey , Fokin Sergei , Petroni Giulio 
Published: November 2021

SummaryHolosporales are an alphaproteobacterial lineage encompassing bacteria obligatorily associated with multiple diverse eukaryotes. For most representatives, little is known on the interactions with their hosts. In this study, we characterized a novel Holosporales symbiont of the ciliate Paramecium polycaryum. This bacterium inhabits the host cytoplasm, frequently forming quite large aggregates. Possibly due to such aggregates, host cells sometimes displayed lethal division defects. The symbiont was also able to experimentally stably infect another Paramecium polycaryum strain. The bacterium is phylogenetically related with symbionts of other ciliates and diplonemids, forming a putatively fast‐evolving clade within the family Holosporaceae. Similarly to many close relatives, it presents a very small genome (<600 kbp), and, accordingly, a limited predicted metabolism, implying a heavy dependence on Paramecium, thanks also to some specialized membrane transporters. Characterized features, including the presence of specific secretion systems, are overall suggestive of a mild parasitic effect on the host. From an evolutionary perspective, a potential ancestral trend towards pronounced genome reduction and possibly linked to parasitism could be inferred, at least among fast‐evolving Holosporaceae, with some lineage‐specific traits. Interestingly, similar convergent features could be observed in other host‐associated lineages, in particular Rickettsiales among Alphaproteobacteria.
Fragmented QRS is associated with ventricular arrhythmias in heart failure patients: A systematic review and meta‐analysis
Authors: Engstrom Nathan , Dobson Geoffrey , Ng Kevin , Letson Hayley 
Published: November 2021

AbstractIntroductionMany primary prevention heart failure (HF) patients with an implantable cardiac defibrillator (ICD) rarely experience life‐threatening ventricular arrhythmias (VA). New strategies are required to identify patients most at risk of VA and sudden cardiac death who would benefit from an ICD. One potential method is the detection of fragmented QRS (fQRS) on the electrocardiogram. The aim was to assess the predictive capacity of fQRS for VA and mortality in ischemic (ICM) and non‐ischemic cardiomyopathy (NICM) primary prevention HF patients.Methods and ResultsA systematic review and meta‐analysis of studies examining fQRS in HF patients with or without an ICD who met primary prevention indications with reduced ejection fraction ≤40%. Outcome measures were VA (or appropriate ICD therapy) and all‐cause mortality. Ten studies involving 3885 patients were included for analysis. Most patients were male with non‐fQRS patients being significantly younger (−1.5[−2.66, −0.42], p = .03). Diabetes was more likely in fQRS patients (1.12[1.01, 1.25], p = .03) while non‐fQRS patients were 28% more likely to have a history of atrial fibrillation (0.82[0.67,1.00], p = .05). Ventricular arrhythmias were significantly 1.5 times more likely in patients with fQRS (1.51[1.02, 2.25], p = .04). HF patients were 1.7 times more likely to die of any cause if fQRS was present (1.68[1.13, 2.52], p = .01). NICM patients with fQRS have a significant 2.6‐fold increased incidence of death compared with ICM patients (2.55[1.63, 3.98], p < .0001).ConclusionfQRS is associated with VA and all‐cause mortality and may be a novel marker in the risk stratification of primary prevention HF patients indicated for ICD implantation.
Sexual dimorphism in prostacyclin‐mimetic responses within rat mesenteric arteries: A novel role for KV7.1 in shaping IP receptor‐mediated relaxation
Authors: Baldwin Samuel N. , Forrester Elizabeth A. , McEwan Lauren , Greenwood Iain A. 
Published: November 2021

Background and PurposeProstacyclin mimetics express potent vasoactive effects via prostanoid receptors that are not unequivocally defined, as to date no study has considered sex as a factor. The aim of this study was to determine the contribution of IP and EP3 prostanoid receptors to prostacyclin mimetic iloprost‐mediated responses, whether KV7.1–5 channels represent downstream targets of selective prostacyclin‐IP‐receptor agonist MRE‐269 and the impact of the oestrus cycle on vascular reactivity.Experimental ApproachWithin second‐order mesenteric arteries from male and female Wistar rats, we determined (1) relative mRNA transcripts for EP1–4 (Ptger1–4), IP (Ptgi) and TXA2 (Tbxa) prostanoid receptors via RT‐qPCR; (2) the effect of iloprost, MRE‐269, isoprenaline and ML277 on precontracted arterial tone in the presence of inhibitors of prostanoid receptors, potassium channels and the molecular interference of KV7.1 via wire‐myograph; (3) oestrus cycle stage via histological changes in cervical cell preparations.Key ResultsIloprost evoked a biphasic response in male mesenteric arteries, at concentrations ≤100 nmol·L−1 relaxing, then contracting the vessel at concentration ≥300 nmol·L−1, a process attributed to IP and EP3 receptors respectively. Secondary contraction was absent in the females, which was associated with a reduction in Ptger3. Pharmacological inhibition and molecular interference of KV7.1 significantly attenuated relaxations produced by the selective IP receptor agonist MRE‐269 in male and female Wistar in dioestrus/metoestrus, but not pro‐oestrus/oestrus.Conclusions and ImplicationsStark sexual dimorphisms in iloprost‐mediated vasoactive responses are present within mesenteric arteries. KV7.1 is implicated in IP receptor‐mediated vasorelaxation and is impaired by the oestrus cycle.
α‐Adrenoceptor stimulation attenuates melanoma growth in mice
Authors: Maccari Sonia , Buoncervello Maria , Ascione Barbara , Stati Tonino , Macchia Daniele , Fidanza Stefano , Catalano Liviana , Matarrese Paola , Gabriele Lucia , Marano Giuseppe 
Published: November 2021

Background and PurposeRecently, β‐adrenoceptor blockade has emerged as a potential strategy to inhibit melanoma growth. It remains to be ascertained whether β‐adrenoceptor stimulation by circulating catecholamines increases melanoma growth in mice.Experimental ApproachB16F10 melanoma‐bearing mice were used to evaluate effects of adrenaline and specific adrenoceptor (AR) ligands on tumour volume. AR expression and effects of AR ligands on cell viability, production of mitochondrial reactive oxygen species (mROS), and proliferation activity in B16F10 cells, were determined by biochemical analyses.Key ResultsReal‐time polymerase chain reaction (qPCR) analyses revealed that B16F10 cells express α1B‐, α2A‐, α2B‐ and β2‐ARs. We found that treatment with the α‐ and β‐AR agonist adrenaline or with the synthetic catecholamine isoprenaline, which selectively stimulates β‐ARs, did not affect melanoma growth. Conversely, adrenaline reduced tumour growth in mice cotreated with propranolol, a β1β2‐AR antagonist. Adrenaline had no effect in tumour‐bearing β1β2‐AR knockout mice, in which β1‐ and β2‐ARs are lacking, but it reduced tumour growth when co‐administered with propranolol suggesting that tumour β2‐ARs negatively regulate adrenaline antitumour activity. Additionally, we found that α1‐AR stimulation with cirazoline yielded a decrease in B16F10 melanoma size. These effects on melanoma growth were paralleled by reduced cell viability and proliferation activity as well as increased mROS production in α1‐AR‐stimulated B16F10 cells. Decreased viability, proliferation and mitochondrial function in B16F10 cells also occurred after α2‐AR stimulation by α2‐AR agonist ST91.Conclusions and ImplicationsIn the B16F10 melanoma model, stimulation of α‐AR subtypes yields in vivo and in vitro anticancer activity.
Bi‐allelic variants in MDH2: Expanding the clinical phenotype
Authors: Ticci Chiara , Nesti Claudia , Rubegni Anna , Doccini Stefano , Baldacci Jacopo , Dal Canto Flavio , Ragni Luca , Cordelli Duccio M. , Donati Maria Alice , Santorelli Filippo M. 
Published: November 2021

AbstractBi‐allelic alterations in the MDH2 gene have recently been reported in three unrelated toddlers with early‐onset severe encephalopathy. Here, we describe a new case of a child carrying novel variants in MDH2. This child presented with early‐onset encephalocardiopathy requiring heart transplant and showed cerebellar ataxia and drug‐responsive epilepsy; his family history was significant for multiple cancers, a feature often associated with monoallelic variants in MDH2. Functional studies in cultured skin fibroblasts from the proband showed reduced protein levels and impaired enzyme activity, further corroborating the genetic results. The relatively mild neurological presentation and severe cardiac manifestations requiring heart transplant distinguish this case from previous reports. This patient thus expands the spectrum of clinical features associated with MDH2 variants.
Increasing soil organic carbon pools and wheat yields by optimising tillage and fertilisation on the Loess Plateau in China
Authors: Zhang Xia , Wang Minge , Zhang Dandan , Zhang Yulin , Wang Xudong 
Published: November 2021

AbstractThe effect of conservation tillage on soil organic carbon (SOC) sequestration and crop production is controversial in semi‐arid areas. In addition, fertilisation is another essential factor affecting soil carbon pool and crop yields. We sought to explore the changes of SOC pool and crop productivity after optimising fertilisation and tillage. An 11‐year field experiment on the Loess Plateau in China was conducted to evaluate the effects of (i) fertilisation (balanced fertilisation, low fertilisation, conventional fertilisation) and (ii) tillage (no‐tillage, subsoiling, ploughing) on input‐C, SOC stocks, labile C fractions, C pool management index (CMI) and wheat yield. SOC stock accumulation at 0–35 cm depth under balanced fertilisation increased by 59% compared to conventional fertilisation due to the larger amount and stabilisation efficiency of input‐C. Simultaneously, balanced fertilisation increased labile C contents and CMI at 0–10 cm depth. For tillage, no‐tillage and subsoiling improved input‐C and its stabilisation efficiency, and increased SOC stocks compared to ploughing. Balanced fertilisation combined with no‐tillage or subsoiling produced greater SOC stocks at 0–35 cm depth compared to other treatments. No‐tillage increased labile C contents and CMI at 0–10 cm depth, while subsoiling increased labile C contents and CMI at 0–10 and 35–50 cm depths. Wheat yield and sustainable yield index (SYI) were positively correlated with SOC, and the effect of SOC contributed to SYI largely through indirect effects of dissolved organic C and particulate organic C. Wheat yield and SYI were increased by optimising fertilisation and tillage, and the greatest yield was under balanced fertilisation combined with the subsoiling treatment. Our findings suggested that balanced fertilisation combined with subsoiling was an effective practice for increasing SOC sequestration, soil quality, wheat yields and had great potential application on the Loess Plateau in China.Highlights
C sequestration under conservation tillage and fertilisation are controversial in semi‐arid areas.
Balanced fertilisation promoted SOC sequestration in no‐tillage and subsoiling treatments.
Subsoiling improved soil quality at 0–10 and 35–50 cm depths due to the greater SOC and labile C.
Subsoiling was superior to no‐tillage and ploughing in maintaining crop productivity.
In vitro flow rates through five different catheters intended for intravenous use in horses at two different heights
Authors: Lord S. , Duncan J. , Gozalo‐Marcilla M. , Woodhouse K. 
Published: November 2021

SummaryBackgroundFluid therapy is an important component of equine practice. The choice of intravenous catheter is likely to impact fluid flow rates, which is of relevance in clinical cases.Objectives(i) To assess fluid flow rates through five different equine catheters; (ii) to evaluate the impact of height on fluid flow rates and (iii) to compare agreement of flow rates achieved through identical catheters.Study designIn vitro experimental study.MethodsFlow rates were measured through five different equine catheters (2 × 14, 13, 12 and 10‐gauge) at 150 and 200 cm from ground level. Each catheter was attached to a standardised fluid administration system, time taken to reach 1000 g of fluids was measured. Three catheters were used to assess the agreement between identical catheters. Statistical analysis: (i) one‐way ANOVA assessed whether catheter type influenced flow rate and a post‐hoc Tukey's test compared mean flow rates with all other flow rates; (ii) two‐way ANOVA assessed whether height and catheter type influenced the flow rate. Finally, (iii) an intraclass correlation assessed how closely flow rates from identical catheters resembled each other.Results(i) The fastest mean flow rates were achieved through the 10‐gauge catheter at 150 (14.1 L/h) and 200 cm (17.8 L/h). (ii) Mean flow rates through all five catheters increased by a range of 25.4–28.6% at 200 vs. 150 cm. (iii) There was excellent agreement between mean fluid rates through identical catheters (intraclass correlation 0.994–0.998).Main limitationsFlow rates achievable in vivo are likely to be lower. We used water which may have a different viscosity compared with fluids used commonly in equine practice.ConclusionsFluid flow rates can be increased using wider bore catheters and increasing the height of the fluid bag. There is excellent agreement between fluid flow rates through identical catheters.
A multi‐tenancy and robust workflow management system
Authors: Ding Weilong , Liu Ji , Yang Zhongguo , Lv Bo , Li Han , Xu Hanchuan 
Published: November 2021

AbstractWorkflow management system (WfMS) in cloud always works as platform as a service to manage customized business processes for massive enterprises. In big data era, non‐functional guarantees of such systems are significant when facing a large number of users and concurrent requests. It is not trivial to support multi‐tenancy and hold high‐availability, because traditional architecture cannot simultaneously satisfy requirements about data isolation and runtime efficiency. In this paper, a modularized distributed workflow management system is proposed, which considers both multi‐tenancy and high‐availability in storage and engine parts of the system. A multiple‐worker‐with‐separate‐schema mechanism is defined to jointly manage the data for tenants, and a proactive strategy is presented to intelligently dispatch large concurrent requests from users to engine workers. After extensive case studies and experiments in practical scenes, our system deployed on modest machines is proved to support tens of thousands of tenants, second‐level response time for 10 K concurrency, and no‐human‐intervened failure recovery for a fail‐stop system node.
Molecular dating of the blood pigment hemocyanin provides new insight into the origin of animals
Authors: Maria Costa‐Paiva Elisa , Mello Beatriz , Santos Bezerra Bruno , Coates Christopher J. , Halanych Kenneth M. , Brown Federico , de Moraes Leme Juliana , Trindade Ricardo I. F. 
Published: November 2021

AbstractThe Neoproterozoic included changes in oceanic redox conditions, the configuration of continents and climate, extreme ice ages (Sturtian and Marinoan), and the rise of complex life forms. A much‐debated topic in geobiology concerns the influence of atmospheric oxygenation on Earth and the origin and diversification of animal lineages, with the most widely popularized hypotheses relying on causal links between oxygen levels and the rise of animals. The vast majority of extant animals use aerobic metabolism for growth and homeostasis; hence, the binding and transportation of oxygen represent a vital physiological task. Considering the blood pigment hemocyanin (Hc) is present in sponges and ctenophores, and likely to be present in the common ancestor of animals, we investigated the evolution and date of Hc emergence using bioinformatics approaches on both transcriptomic and genomic data. Bayesian molecular dating suggested that the ancestral animal Hc gene arose approximately 881 Ma during the Tonian Period (1000–720 Ma), prior to the extreme glaciation events of the Cryogenian Period (720–635 Ma). This result is corroborated by a recently discovered fossil of a putative sponge ~890 Ma and modern molecular dating for the origin of metazoans of ~1,000–650 Ma (but does contradict previous inferences regarding the origin of Hc ~700–600 Ma). Our data reveal that crown‐group animals already possessed hemocyanin‐like blood pigments, which may have enhanced the oxygen‐carrying capacity of these animals in hypoxic environments at that time or acted in the transport of hormones, detoxification of heavy metals, and immunity pathways.