bluuebunny/crossref_metadata_2025_split huggingface dataset:
High expression of the MADS-box geneVRT2increases the number of rudimentary basal spikelets in wheat
Authors: Backhaus Anna E , Lister Ashleigh , Tomkins Melissa , Adamski Nikolai M , Simmonds James , Macaulay Iain , Morris Richard J , Haerty Wilfried , Uauy Cristobal 
Published: April 2022

AbstractSpikelets are the fundamental building blocks of Poaceae inflorescences, and their development and branching patterns determine the various inflorescence architectures and grain yield of grasses. In wheat (Triticum aestivum), the central spikelets produce the most and largest grains, while spikelet size gradually decreases acropetally and basipetally, giving rise to the characteristic lanceolate shape of wheat spikes. The acropetal gradient corresponds with the developmental age of spikelets; however, the basal spikelets are developed first, and the cause of their small size and rudimentary development is unclear. Here, we adapted G&T-seq, a low-input transcriptomics approach, to characterize gene expression profiles within spatial sections of individual spikes before and after the establishment of the lanceolate shape. We observed larger differences in gene expression profiles between the apical, central, and basal sections of a single spike than between any section belonging to consecutive developmental time points. We found that SHORT VEGETATIVE PHASE MADS-box transcription factors, including VEGETATIVE TO REPRODUCTIVE TRANSITION 2 (VRT-A2), are expressed highest in the basal section of the wheat spike and display the opposite expression gradient to flowering E-class SEPALLATA1 genes. Based on multi-year field trials and transgenic lines, we show that higher expression of VRT-A2 in the basal sections of the spike is associated with increased numbers of rudimentary basal spikelets. Our results, supported by computational modeling, suggest that the delayed transition of basal spikelets from vegetative to floral developmental programs results in the lanceolate shape of wheat spikes. This study highlights the value of spatially resolved transcriptomics to gain insights into developmental genetics pathways of grass inflorescences.
All-cause and cause-specific mortality in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis: a nationwide registry study
Authors: Kerola Anne M , Kazemi Amirhossein , Rollefstad Silvia , Lillegraven Siri , Sexton Joseph , Wibetoe Grunde , Haavardsholm Espen A , Kvien Tore K , Semb Anne Grete 
Published: April 2022

Abstract

Objectives
To explore mortality and causes of death among Norwegian patients with RA, PsA and axial spondyloarthritis (axSpA) compared with the general population by conducting a nationwide registry-based cohort study.

Methods
Patients with RA, PsA and axSpA were identified from the Norwegian Patient Registry based on ICD-10 codes between 2008 and 2017. Using age as the time variable, all-cause and cause-specific mortality were estimated between 2010 and 2017 with the Kaplan–Meier estimator and the cumulative incidence competing risk method, respectively. Sex-, education level-, health region- and age group-adjusted hazard ratios (HRs) for mortality were estimated using Cox regression models.

Results
We identified 36 095 RA, 18 700 PsA and 16 524 axSpA patients (70%, 53% and 45% women, respectively). RA and axSpA were associated with increased all-cause mortality (HR 1.45 [95% CI: 1.41, 1.48] and HR 1.38 [95% CI: 1.28, 1.38], respectively). Women but not men with PsA had a slightly increased mortality rate (HR 1.10 [95% CI: 1.00, 1.21] among women and 1.02 [95% CI: 0.93, 1.11] among men). For all patient groups as well as for the general population, the three leading causes of death were cardiovascular diseases, neoplasms and respiratory diseases. RA patients had increased mortality from all of these causes, while axSpA patients had increased mortality from cardiovascular and respiratory diseases.

Conclusion
Even in the era of modern treatments for IJDs, patients with RA and axSpA still have shortened life expectancy. Our findings warrant further attention to the prevention and management of comorbidities.
Implications of sympathetic activation for objective versus self-reported daytime sleepiness in obstructive sleep apnea
Authors: Chen Baixin , Somers Virend K , Sun Qimeng , Dai Yanyuan , Li Yun 
Published: April 2022

Abstract

Study Objectives
Objective excessive daytime sleepiness (EDS) is associated with systemic inflammation and a higher risk of cardiometabolic morbidity in obstructive sleep apnea (OSA). We hypothesized that OSA with objective EDS is associated with higher levels of sympathetic nerve activity (SNA) when compared with self-reported EDS. We, therefore, examined the associations between objective and self-reported EDS with SNA in patients with OSA.

Methods
We studied 147 consecutive male patients with OSA from the institutional sleep clinic. Objective EDS and self-reported EDS were defined based on Multiple Sleep Latency Test (MSLT) latency ≤ 8 minutes and Epworth Sleepiness Scale (ESS) &gt; 10, respectively. Twenty-four-hour urinary norepinephrine was used for assessing SNA. Blood pressure (BP) was measured both in the evening and in the morning.

Results
Twenty-four-hour urinary norepinephrine was significantly higher in patients with OSA with objective EDS compared with those without objective EDS (p = 0.034), whereas it was lower in patients with OSA with self-reported EDS compared with those without self-reported EDS (p = 0.038) after adjusting for confounders. Differences in the sympathetic drive were most striking in those with an objective but not self-reported EDS versus those with self-reported but not objective EDS (p = 0.002). Moreover, shorter MSLT latency was significantly associated with higher diastolic BP (β = −0.156, p = 0.049) but not systolic BP. No significant association between ESS scores and BP was observed.

Conclusions
Objective, but not self-reported EDS, is associated with increased SNA and diastolic BP among males with OSA, suggesting that objective EDS is a more severe phenotype of OSA that is accompanied by higher sympathetic drive, higher BP, and possibly greater cardiovascular morbidity and mortality.
The past, present, and future of sleep measurement in mild cognitive impairment and early dementia—towards a core outcome set: a scoping review
Authors: Blackman Jonathan , Morrison Hamish Duncan , Lloyd Katherine , Gimson Amy , Banerjee Luke Vikram , Green Sebastian , Cousins Rebecca , Rudd Sarah , Harding Sam , Coulthard Elizabeth 
Published: April 2022

AbstractStudy ObjectivesSleep abnormalities emerge early in dementia and may accelerate cognitive decline. Their accurate characterization may facilitate earlier clinical identification of dementia and allow for assessment of sleep intervention efficacy. This scoping review determines how sleep is currently measured and reported in Mild Cognitive Impairment (MCI) and early dementia, as a basis for future core outcome alignment.MethodsThis review follows the PRISMA Guidelines for Scoping Reviews. CINAHL, Embase, Medline, Psychinfo, and British Nursing Index databases were searched from inception—March 12, 2021. Included studies had participants diagnosed with MCI and early dementia and reported on sleep as a key objective/ outcome measure.ResultsNineteen thousand five hundred and ninety-six titles were returned following duplicate removal with 188 studies [N] included in final analysis. Sleep data was reported on 17 139 unique, diagnostically diverse participants (n). “Unspecified MCI” was the most common diagnosis amongst patients with MCI (n = 5003, 60.6%). Despite technological advances, sleep was measured most commonly by validated questionnaires (n = 12 586, N = 131). Fewer participants underwent polysomnography (PSG) (n = 3492, N = 88) and actigraphy (n = 3359, N = 38) with little adoption of non-PSG electroencephalograms (EEG) (n = 74, N = 3). Sleep outcome parameters were reported heterogeneously. 62/165 (37.6%) were described only once in the literature (33/60 (60%) in interventional studies). There was underrepresentation of circadian (n = 725, N = 25) and micro-architectural (n = 360, N = 12) sleep parameters.ConclusionsAlongside under-researched areas, there is a need for more detailed diagnostic characterization. Due to outcome heterogeneity, we advocate for international consensus on core sleep outcome parameters to support causal inference and comparison of therapeutic sleep interventions.
Modelling behaviour in intergroup conflicts: a review of microeconomic approaches
Authors: Rusch Hannes 
Published: April 2022

Microeconomic modelling offers a powerful formal toolbox for analysing the complexities of real-world intergroup relations and conflicts. One important class of models scrutinizes individuals’ valuations of different group memberships, attitudes towards members of different groups and preferences for resource distribution in group contexts. A second broad class uses game theoretical methods to study strategic interactions within and between groups of individuals in contest and in conflict. After a concise discussion of some essential peculiarities of microeconomic modelling, this review provides an overview of the pertinent literatures in economics, highlights instructive examples of central model types and points out several ways forward.This article is part of the theme issue ‘Intergroup conflict across taxa’.
Oxytocin has ‘tend-and-defend’ functionality in group conflict across social vertebrates
Authors: Triki Zegni , Daughters Katie , De Dreu Carsten K. W. 
Published: April 2022

Across vertebrate species, intergroup conflict confronts individuals with a tension between group interests best served by participation in conflict and personal interest best served by not participating. Here, we identify the neurohormone oxytocin as pivotal to the neurobiological regulation of this tension in distinctly different group-living vertebrates, including fishes, birds, rodents, non-human primates and humans. In the context of intergroup conflict, a review of emerging work on pro-sociality suggests that oxytocin and its fish and birds homologues, isotocin and mesotocin, respectively, can elicit participation in group conflict and aggression. This is because it amplifies (i) concern for the interests of genetically related or culturally similar ‘in-group’ others and (ii) willingness to defend against outside intruders and enemy conspecifics. Across a range of social vertebrates, oxytocin can induce aggressive behaviour to ‘tend-and-defend’ the in-group during intergroup contests.
This article is part of the theme issue ‘Intergroup conflict across taxa’.
Sex bias in intergroup conflict and collective movements among social mammals: male warriors and female guides
Authors: Smith Jennifer E. , Fichtel Claudia , Holmes Rose K. , Kappeler Peter M. , van Vugt Mark , Jaeggi Adrian V. 
Published: April 2022

Intergroup conflict is a major evolutionary force shaping animal and human societies. Males and females should, on average, experience different costs and benefits for participating in collective action. Specifically, among mammals, male fitness is generally limited by access to mates whereas females are limited by access to food and safety. Here we analyse sex biases among 72 species of group-living mammals in two contexts: intergroup conflict and collective movements. Our comparative phylogenetic analyses show that the modal mammalian pattern is male-biased participation in intergroup conflict and female-biased leadership in collective movements. However, the probability of male-biased participation in intergroup conflicts decreased and female-biased participation increased with female-biased leadership in movements. Thus, female-biased participation in intergroup conflict only emerged in species with female-biased leadership in collective movements, such as in spotted hyenas and some lemurs. Sex differences are probably attributable to costs and benefits of participating in collective movements (e.g. towards food, water, safety) and intergroup conflict (e.g. access to mates or resources, risk of injury). Our comparative review offers new insights into the factors shaping sex bias in leadership across social mammals and is consistent with the ‘male warrior hypothesis' which posits evolved sex differences in human intergroup psychology.
This article is part of the theme issue ‘Intergroup conflict across taxa’.
Safety, Immunologic Effects and Clinical Response in a Phase I Trial of Umbilical Cord Mesenchymal Stromal Cells in Patients with Treatment Refractory Systemic Lupus Erythematosus
Authors: Kamen Diane , Wallace Caroline , Li Zihai , Wyatt Megan , Paulos Crystal , Wei Chungwen , Wang Hongjun , Sanz Inaki , Wolf Bethany J , Nietert Paul J , Robinson Angela , Gilkeson Gary 
Published: April 2022

AbstractBackgroundReports of clinical improvement following mesenchymal stromal cell (MSC) infusions in refractory lupus patients at a single center in China led us to perform an explorative Phase I trial of umbilical cord derived MSCs in patients refractory to six months of immunosuppressive therapy.MethodsSix women with a SLEDAI>6, having failed standard of care therapy, received one IV infusion of 1×106 MSCs/kg of body weight. They maintained their current immunosuppressives, but their physician was allowed to adjust corticosteroids initially for symptom management. The clinical endpoint was an SRI of 4 with no new BILAG As and no increase in Physician Global Assessment score of >0.3 with tapering of prednisone to 10mg or less by 20 weeks.ResultsOf 6 patients, 5 (83.3%; 95% CI = 35.9% to 99.6%) achieved the clinical endpoint of an SRI of 4. Adverse events were minimal. Mechanistic studies revealed significant reductions in CD27IgD negative B cells, switched memory B cells and activated naïve B cells with increased transitional B cells in the 5 patients who met the endpoint. There was a trend towards decreased autoantibody levels in specific patients. One patient had an increase in their Helios+Treg cells, but no other significant T cell changes were noted. GARP-TGFβ complexes were significantly increased following the MSC infusions. The B cell changes and the GARP-TGFβ increase were significantly correlated with SLEDAI scores.ConclusionThis pilot trial suggests that UC MSC infusions are safe and may have efficacy in lupus. The B cell and GARP-TGFβ changes provide insight into mechanisms by which MSCs may impact disease.Trial RegistrationNCT03171194FundingThis study was funded by a grant from the Lupus Foundation of America and NIH UL1 RR029882
Tegaserod maleate suppresses the growth of gastric cancer in vivo and in vitro by targeting MEK1/2
Authors: Wang Zitong , Chen Yingying , Li Xiaoyu , Zhang Yuhan , Zhao Xiaokun , Zhou Hao , Lu Xuebo , Zhao Lili , Yuan Qiang , Shi Yunshu , Zhao Jimin , Dong Ziming , Jiang Yanan , Liu Kangdong 
Published: April 2022

AbstractGastric cancer (GC), ranking fifth in global incidence and fourth in mortality. The current treatments for GC include surgery, chemotherapy, and radiotherapy. Although management and treatment strategies for GC have been improved over the last decade, the overall five-year survival rate remains less than 30%. Therefore, there is an urgent need to find novel therapeutic or preventive strategies that can increase GC patient survival rates. In the current study, we found that tegaserod maleate, a FDA-approved drug, could inhibit the proliferation of gastric cancer cells. Tegaserod maleate binds to MEK1 /2 and inhibits MEK1 /2 kinase activity. Moreover, the construction of CRISPER/Cas9 cell line further verified that tegaserod maleate depended on MEK1 /2 to inhibit the progress of gastric cancer. Notably, we found that tegaserod maleate suppressed tumor growth in patient-derived gastric xenograft (PDX) mouse model. We also compared tegaserod maleate with trametinib, a clinical MEK1/2 inhibitor, and comfirmed that tegaserod maleate have the same effect in inhibiting tumor volume and tumor weight. Our findings suggest that tegaserod maleate can inhibit GC proliferation by targeting MEK1/2.
NSMCE2, a Novel Super-Enhancer Regulated Gene, is Linked to Poor Prognosis and Therapy Resistance in Breast Cancer
Authors: Di Benedetto Carolina , Oh Justin , Choudhery Zainab , Shi Weiquan , Valdes Gilmer , Betancur Paola 
Published: April 2022

AbstractIn this study, we identified two novel super-enhancer associated genes: NSMCE2 and MAL2, highly upregulated in breast tumors, for which high RNA levels significantly and specifically correlate with breast cancer patients’ poor prognosis. To approach this, we took advantage of existing datasets containing super-enhancers associated genes identified in primary breast tumors and public databases comprising gene expression, genomic and clinical outcomes for patients diagnosed with breast cancer. Through in-vitro pharmacological super-enhancer disruption assays in breast cancer cells we confirmed that super-enhancers are involved in NSMCE2 and MAL2 transcript upregulation and through bioinformatics we found that high levels of NSMCE2 strongly associate with poor response to chemotherapy. This was observed especially for patients diagnosed with aggressive triple negative and HER2 positive tumor types. Finally, we showed that treating breast cancer cells with chemotherapeutic agents while simultaneously decreasing NSMCE2 gene expression by super-enhancer blockade or by directly silencing it, reduces cell viability thus increasing the effectiveness of chemotherapy. Our results indicate that moderating the transcript levels of the novel identified super-enhancer associated gene NSMCE2 could improve patients’ response to standard chemotherapy and, consequently, may improve disease outcome. In summary by mining existing public breast cancer datasets, our work demonstrates that searching for super-enhancer regulated genes and their association to patients’ survival and response to treatment, could be an effective method for identifying a signature of tumor specific -not frequently mutated, but super-enhancer dysregulated genes. Our approach offers a new avenue to identify novel biomarkers of poor prognosis and potential pharmacological targets for improving cancer treatment.
The influence of BPM-supportive culture and individual process orientation on process conformance
Authors: Benraad Minou , Ozkan Baris , Turetken Oktay , Vanderfeesten Irene 
Published: April 2022

PurposeOrganizations rely on their business processes to achieve their business objectives and ensure compliance with relevant laws and regulations. Hence, conformance to process specifications is essential to remain compliant. Various factors influence an organization’s ability to operate in conformance to its process specifications. This study investigates the influence of business process management (BPM)-supportive culture and individual process orientation on process conformance.Design/methodology/approachA construct was created for perceived process conformance and two constructs were selected from literature to represent BPM-supportive culture and individual process orientation. A survey was conducted with 178 employees of a global enterprise, hypotheses were formulated, and a statistical model was constructed and validated.FindingsResults pinpoint the key role of the BPM-supportive culture in influencing both individual process orientation and conformance. Individual process orientation is also found to have a significant influence on process conformance. The findings provide additional evidence for the significance of human-related aspects of BPM in achieving BPM success.Originality/valueThe contributions of this paper help better understand how soft factors of BPM contribute to employees’ process conformance drawing on and relating concepts of BPM and organizational routines.
The cultural dimension in companies' leverage. New evidence using panel data for a European macroeconomic context
Authors: Neves Maria Elisabete , Almeida Daniela , Vieira Elisabete S. 
Published: April 2022

PurposeThe main objective of this work is to show that the traditional specific characteristics of companies as well as cultural and religious dimensions can influence the leverage of companies in different macro-environmental systems.Design/methodology/approachTo achieve this aim, the authors have used data from 1.568 firms from 7 European countries between 2010 and 2016, and the models were estimated by using panel data methodology, specifically the generalized method of moments (GMM) estimation method by Arellano and Bover (1995) and Blundell and Bond (1998).FindingsOverall, the empirical results point out that the cultural moderating factors are essential in determining companies' capital structure, regardless of the country's legal origin. The study results also show that traditional variables, intrinsic to management, macroeconomic environment and religion, have a central role in capital structure, namely for the civilian countries.Originality/valueAs far as the authors know, this is the first work that uses, in addition to the traditional specific characteristics of companies, cultural dimensions and religion, as determinants of debt levels, in different legal systems for Europe.
The impact of COVID-19 on the operations and management of NGOs: resilience and recommendations
Authors: Asogwa Ikenna Elias , Varua Maria Estela , Datt Rina , Humphreys Peter 
Published: April 2022

Purpose
The COVID-19 pandemic has made humanity contend with the negative footprint of its activities in which social justice, ecological integrity and economic stability are compromised. This study aims to investigate the impact of COVID-19 on the operation and management of non-governmental organisations (NGOs) in Nigeria.

Design/methodology/approach
Multiple case study research design was used in the study with interviews from 25 senior-level management staff of NGOs.

Findings
The analysis revealed that COVID-19 impacts NGOs both negatively and positively. Dominant among the negative impacts are a decline in health-seeking behaviours, low programme implementation, increased cost and wastages resulting from PPE, transition to virtual meetings, a decline in capacity building and staff burnout/pressure. However, some positive impacts include increased efficiency through the use of virtual innovations, peer-to-peer intervention through the establishment of networks, flexibility and prompt adaptation to the crisis, prudent management of available resources, etc. This research contributes to theory and practice.

Research limitations/implications
Conducting this research and recruiting participants at the height of COVID-19 in Nigeria, in adherence to the prevention guidelines, constituted a considerable limitation to the study.

Practical implications
Although the identified impact could be useful in framing operational policies and guidelines, the study highlights a salient future outlook with policy implications for both the governance of NGOs and the facilitation of sustainable development goals by the government.

Originality/value
Although researchers continue to explore the impact of COVID-19, none has considered the NGO sector, especially in developing countries, and with a focus on providing evidence-backed resilience practices for the future.