bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolomic signature of the Dravet syndrome: A genetic mouse model study
Authors: Miljanovic Nina , van Dijk Roelof Maarten , Buchecker Verena , Potschka Heidrun
Published: July 2021

Objective

Alterations in metabolic homeostasis can contribute to neuronal hyperexcitability and seizure susceptibility. Although the pivotal role of impaired bioenergetics is obvious in metabolic epilepsies, there is a gap of knowledge regarding secondary changes in metabolite patterns as a result of genetic Scn1a deficiency and ketogenic diet in the Dravet syndrome.

Methods

A comprehensive untargeted metabolomics analysis, along with assessment of epileptiform activity and behavioral tests, was completed in a Dravet mouse model. Data sets were compared between animals on a control and a ketogenic diet, and metabolic alterations associated with Dravet mice phenotype and ketogenic diet were identified.

Results

Hippocampal metabolomic data revealed complex alterations in energy metabolism with an effect of the genotype on concentrations of glucose and several glycolysis and tricarboxylic acid (TCA) cycle intermediates. Although low glucose, lactate, malate, and citrate concentrations became evident, the increase of several intermediates suggested a genotype‐associated activation of catabolic processes with enhanced glycogenolysis and glycolysis. Moreover, we observed an impact on the glutamate/γ‐aminobutyric acid (GABA)‐glutamine cycle with reduced levels of all components along with a shift toward an increased GABA‐to‐glutamate ratio. Further alterations comprised a reduction in hippocampal levels of noradrenaline, corticosterone, and of two bile acids.

Significance

Considering that energy depletion can predominantly compromise the function of GABAergic interneurons, the changes in energy metabolism may contribute to seizure susceptibility and ictogenesis. They may also explain the therapeutic potential of the ketogenic diet, which aims to shift energy metabolism toward a more fat‐based energy supply. Conversely, the increased GABA‐to‐glutamate ratio might serve as an endogenous compensatory mechanism, which can be further supported by GABAergic drugs, representing the mainstay of therapeutic management of Dravet syndrome. In view of a possible neuroprotective function of bile acids, it might be of interest to explore a possible therapeutic potential of bile acid–mediated therapies, already in discussion for neurodegenerative disorders.
Ethical considerations for research on small‐scale fisheries and blue crimes
Authors: Satizábal Paula , Le Billon Philippe , Belhabib Dyhia , Saavedra‐Díaz Lina M. , Figueroa Isabela , Noriega Gina , Bennett Nathan J.
Published: July 2021

Crimes at sea—blue crimes—can have devastating impacts on small‐scale fishing communities. Increasing calls to address “blue crimes” demand more research to address the drivers, patterns, actors and impacts of criminal activities in society and the oceans. This research and policy agenda, however, is not without risks as it might impact individual small‐scale fishers and their communities, exacerbate existing inequalities and contribute to the criminalization of small‐scale fishing practices. This paper discusses the risks and ethical challenges faced by a blue crimes research agenda to improve rather than worsen the plight of small‐scale fishers. We identify eight inter‐related ethical considerations: (i) pay attention to context and forms of involvement, (ii) cultivate reciprocal relationships and collaborations, (iii) evaluate and minimize risks, (iv) integrate storytelling and careful listening, (v) challenge reductionism, (vi) represent people, places, and practices carefully, (vii) follow communication ethics and (viii) consider the legal and policy implications. In light of a review of the literature on blue crimes and small‐scale fisheries, we point to the need for ethically grounded research that is committed to reducing the associated burdens on small‐scale fishers and their communities.
Watching them grow: Intergenerational video‐calling among transnational families in the age of smartphones
Authors: Demirsu Ipek
Published: July 2021

This paper investigates the novel forms of intergenerational communication in transnational families introduced by the widespread use of video‐calls on smartphones. Centring on the kin‐keeping role of the mother, the study analyses 30 semi‐structured interviews with migrant Turkish mothers living in 10 different countries around the world, as the facilitators of video‐calls and intergenerational mediators. It is argued that smartphone mediated video‐calls add new dimensions to the communication that expand the possibilities of self‐expression and bonding for the migrant child with their grandparents in the form of visual performance, spatial sharing and spatio‐temporal longing, while offering new ways of carrying out traditional grandparenting roles in a digitalized setting. Such intergenerational communication is mediated by migrant mothers as manifested through the practice of simultaneous multigenerational communication engaging all three generations on different forms of exchange enabled by the device itself. Although the new generation born into the digital age struggle with the paradox of separation vis‐à‐vis virtual togetherness, everyday video‐calls on smartphones not only help keep the image of ‘family’ alive for the migrant child, they also generate a circumambient virtual setting that permits the transfer of family culture, knowledge and values wherein the younger generation can learn from the parent–grandparent relationship model.
Amphibian thrombocyte‐derived extracellular vesicles, including microRNAs, induce angiogenesis‐related genes in endothelial cells
Authors: Sugimoto Kenkichi , Toume Kayano
Published: July 2021

Thrombocytes circulate in the blood of nonmammalian vertebrates and are involved in hemostasis; however, many detailed characteristics of thrombocytes remain unclear. Recently, we established an amphibian thrombocyte cell line. Here, we report the finding that thrombocytes produce integrin alpha IIb (CD41)‐positive extracellular vesicles (EVs), which include microRNAs (miRs). Flow cytometric analysis showed the expression of CD41+ and phosphatidylserine on the surface of EVs. Nanotracking analysis showed that these CD41+ EVs were approximately 100 nm in diameter. As CD41+ EVs were also observed from African clawed frogs, the production of CD41+ EVs might be common to amphibians. Microarray analysis showed that the CD41+ EVs contain many kinds of miRs. These CD41+ EVs were phagocytosed by endothelial cells and macrophages. qPCR analysis showed that many angiogenesis‐related genes were up‐regulated in CD41+ EV‐treated endothelial cells. Over‐expression of some miRs in the CD41+ EVs increased the proliferation of endothelial cells. These results indicated that thrombocytes produced CD41+ EVs, including miRs, that were received by endothelial cells to induce the expression of angiogenesis‐related genes. These results indicated that the CD41+ EVs produced from thrombocytes act as signaling molecules to repair damaged blood vessels.
Species, subspecies or morph—what was the Canary Islands Oystercatcher?
Authors: Collar Nigel J. , Donald Paul F. , Kirwan Guy M.
Published: July 2021

Taxonomists now usually recognize 10 extant species of oystercatcher Haematopus, plus the extinct Canary Islands Oystercatcher Haematopus meadewaldoi. Molecular data, however, have recently been used to propose meadewaldoi as either a morph or a subspecies of Eurasian Oystercatcher Haematopus ostralegus. The morph option is untenable for multiple reasons, but we also find subspecies rank problematic given (a) the all‐black plumage and (based on our examination of all known specimens) significantly larger bill of the Canarian taxon, and (b) the global acceptance of species rank for Variable Haematopus unicolor and South Island Oystercatchers Haematopus finschi, which are genetically as close as and morphologically closer than meadewaldoi is to ostralegus but which despite their sympatry rarely interbreed. This case illustrates the difficulties of assessing species rank in shallowly divergent, morphologically conservative groups of birds such as the oystercatchers.
A novel atmospheric‐pressure air plasma jet for wound healing
Authors: Guo Peng , Liu Yang , Li Juan , Zhang Nan , Zhou Ming , Li Yi , Zhao Guozhu , Wang Ning , Wang Aiguo , Wang Yupeng , Wang Fujin , Huang Liping
Published: July 2021

Current low‐temperature plasma (LTP) devices essentially use a rare gas source with a short working distance (8 to 20 mm), low gas flow rate (0.12 to 0.3 m3/h), and small effective treatment area (1‐5 cm2), limiting the applications for which LTP can be utilised in clinical therapy. In the present study, a novel type of LTP equipment was developed, having the advantages of a free gas source (surrounding air), long working distance (8 cm), high gas flow rate (10 m3/h), large effective treatment area (20 cm2), and producing an abundance of active substances (NOγ, OH, N2, and O), effectively addressing the shortcomings of current LTP devices. Furthermore, it has been verified that the novel LTP device displays therapeutic efficacy in terms of acceleration of wound healing in normal and Type I diabetic rats, with enhanced wound kinetics, rate of condensation of wound area, and recovery ratio. Cellular and molecular analysis indicated that LTP treatment significantly reduced inflammation and enhanced re‐epithelialization, fibroblast proliferation, deposition of collagen, neovascularization, and expression of TGF‐β, superoxide dismutase, glutathione peroxidase, and catalase in Type I diabetic rats. In conclusion, the novel LTP device provides a convenient and efficient tool for the treatment of clinical wounds.
A tale of two conifers: Migration across a dispersal barrier outpaced regional expansion from refugia
Authors: Fernandez Matias C. , Hu Feng Sheng , Gavin Daniel G. , de Lafontaine Guillaume , Heath Katy D.
Published: July 2021

Aim

Understanding how climate refugia and migration over great distances have facilitated species survival during past climate changes is crucial for evaluating contemporary threats to biodiversity, particularly in the face of dispersal barriers. We address this longstanding question on the refugial origins and post‐glacial development of mesic forests.

Location

Pacific Northwest, North America.

Taxon

Mountain hemlock (Tsuga mertensiana) and western redcedar (Thuja plicata).

Methods

Range‐wide genotyping‐by‐sequencing (ddRADseq) of both study species and a pollen reconstruction of mountain hemlock presence over the last 20,000 years.

Results

Mountain hemlock occurred in two coastal populations (Oregon and Washington) during the glacial maximum, each of which dispersed to the interior (Idaho and British Columbia) during the Holocene. These populations spread in the direction of dominant winds across a barrier of dry, rain‐shadowed valleys. In contrast, for western redcedar, we infer four disparate refugia during the glacial maximum: southern (California), central (Washington), interior (Idaho), and northern (Haida Gwaii islands).

Main conclusions

Despite the presence of pre‐dispersed refugial populations, the majority of the redcedar distribution was colonized by the central population. The history for these two key conifers contrast with many recent studies emphasizing the role of cryptic refugia in colonizing modern species ranges.
Artificial intelligence in educational assessment: ‘Breakthrough? Or buncombe and ballyhoo?’
Authors: Gardner John , O'Leary Michael , Yuan Li
Published: July 2021

Artificial Intelligence is at the heart of modern society with computers now capable of making process decisions in many spheres of human activity. In education, there has been intensive growth in systems that make formal and informal learning an anytime, anywhere activity for billions of people through online open educational resources and massive online open courses. Moreover, new developments in Artificial Intelligence‐related educational assessment are attracting increasing interest as means of improving assessment efficacy and validity, with much attention focusing on the analysis of the large volumes of process data being captured from digital assessment contexts. In evaluating the state of play of Artificial Intelligence in formative and summative educational assessment, this paper offers a critical perspective on the two core applications: automated essay scoring systems and computerized adaptive tests, along with the Big Data analysis approaches to machine learning that underpin them.
The results of health‐related quality of life assessment depend on the prevailing rhythm at the assessment: Experience from the CAPTAF trial (Catheter Ablation Compared with Pharmacological Therapy for Atrial Fibrillation)
Authors: Jansson Victoria , Schwieler Jonas , Bergfeldt Lennart , Kennebäck Göran , Jensen Steen M. , Sciaraffia Elena , Blomström‐Lundqvist Carina
Published: July 2021

Aims

To assess whether the prevailing rhythm at the time of replying to symptom and health‐related quality of life (HR‐QoL) questionnaires impacts the findings.

Method

A total of 150 patients from the randomized Catheter Ablation Compared with Pharmacological Therapy for Atrial Fibrillation‐trial, comparing atrial fibrillation (AF) ablation versus drugs, were included. The effect of the prevailing rhythm on the outcome results of the HR‐QoL 36‐Item Short‐Form Health Survey, the symptom severity questionnaire (SSQ), and the European Heart Rhythm Association (EHRA) score for classification of AF‐related symptoms was assessed.

Results

AF as the prevailing rhythm was independently associated with a significantly lower Vitality score; 18.4 points lower (95% confidence interval −32.7 to −4.1, p = .01) compared with sinus rhythm when adjusted for AF burden, median duration of episode, number of episodes, beta‐blocker use, type of AF, and sex. The presence of AF did not affect the General Health score compared with sinus rhythm, nor did it influence symptoms assessed by the SSQ or EHRA score.

Conclusion

The observation that the presence of AF versus sinus rhythm when conducting HR‐QoL tests had a negative impact on its outcome, leaving symptom‐related questionnaires unaffected, implies that the prevailing rhythm should be taken into account when results of HR‐QoL questionnaires are interpreted.
Hyperglycaemia‐associated macrophage pyroptosis accelerates periodontal inflamm‐aging
Authors: Zhao Pengfei , Yue Ziqi , Nie Lulingxiao , Zhao Zhihao , Wang Qian , Chen Jiao , Wang Qi
Published: July 2021

Aim

Pyroptosis and inflamm‐aging have been newly identified to be involved in diabetic periodontitis. This study aimed to elucidate whether macrophage pyroptosis plays a role in periodontal inflamm‐aging by impacting the senescence of fibroblasts, as well as the potential mechanism via NLR family CARD domain‐containing protein 4 (NLRC4) phosphorylation.

Materials and methods

Diabetes was induced in mice using streptozotocin. Periodontal pyroptosis and senescence were detected using immunohistochemical analysis. Prior to evaluating senescence in human gingival fibroblasts cultured with conditioned medium derived from macrophages, RAW 264.7 macrophages were confirmed to undergo pyroptosis by scanning electron microscopy and gasdermin D (GSDMD) detection. The NLRC4‐related pathway was examined under hyperglycaemic conditions.

Results

Our data showed that macrophage pyroptosis induced the expression of senescent markers in vivo and in vitro. Importantly, clearance of pyroptotic macrophages rescued senescence in fibroblasts. Furthermore, GSDMD activation and pyroptosis in hyperglycaemia were found to be mediated by NLRC4 phosphorylation.

Conclusions

Hyperglycaemia could initially induce macrophage pyroptosis and lead to cellular senescence, thereby critically contributing to periodontal pathogenesis in diabetes. In particular, NLRC4 phosphorylation could be a potential therapeutic target for the inhibition of this process.
Psychiatric comorbidity of eating disorders in children between the ages of 9 and 10
Authors: Convertino Alexandra D. , Blashill Aaron J.
Published: July 2021

Background

Eating disorders exhibit high comorbidity with other psychiatric disorders, most notably mood, substance use, and anxiety disorders. However, most studies examining psychiatric comorbidity are conducted in adolescents and adults. Therefore, the comorbidity among children living with eating disorders is unknown. The aim of this study was to characterize co‐occurring psychiatric disorders with eating disorders in a US sample of children aged 9–10 years old utilizing the Adolescent Brain Cognitive Development study.

Methods

The analytic sample included 11,718 children aged 9–10 years. Anorexia nervosa, bulimia nervosa, binge eating disorder, and other specified feeding and eating disorder subtype diagnoses were examined. Statistical analyses were conducted using complex sampling. Odds ratios and 95% confidence intervals were calculated comparing the likelihood of being diagnosed for a psychiatric disorder when having an eating disorder, as compared to children without an eating disorder, children diagnosed with major depressive disorder, and children diagnosed with posttraumatic stress disorder using binary logistic regression.

Results

Co‐occurring psychiatric disorders were substantially higher in children with eating disorders as compared to children without eating disorders, but not as compared to children diagnosed with major depressive disorder or posttraumatic stress disorder. The most common comorbidities for the eating disorder group were anxiety disorders (71.4%), attention deficit/hyperactivity disorder (47.9%), disruptive/impulse control disorders (45.0%), mood disorders (29.6%), and obsessive‐compulsive disorder (28.8%), largely in line with previous research.

Conclusions

This study extends prior research finding high rates of comorbidity in eating disorders, specifically with anxiety, mood, and disruptive/impulse control disorders. Clinicians assessing for psychiatric disorders should be aware that eating disorders can occur in children 9 and 10 years old and are associated with severe comorbidity. Referrals for specialty mental health care should be considered.
Proteomic characterization of serum proteins from Atlantic salmon (Salmo salar L.) from an outbreak with cardiomyopathy syndrome
Authors: Costa Janina Z. , del Pozo Jorge , McLean Kevin , Inglis Neil , Sourd Philippe , Bordeianu Andrei , Thompson Kim D.
Published: July 2021

Cardiomyopathy syndrome (CMS), caused by piscine myocarditis virus (PMCV), is a serious challenge to Atlantic salmon (Salmo salar L.) aquaculture. Regrettably, husbandry techniques are the only tool to manage CMS outbreaks, and no prophylactic measures are available at present. Early diagnosis of CMS is therefore desirable, preferably with non‐lethal diagnostic methods, such as serum biomarkers. To identify candidate biomarkers for CMS, the protein content of pools of sera (4 fish/pool) from salmon with a CMS outbreak (3 pools) and from clinically healthy salmon (3 pools) was compared using liquid chromatography–electrospray ionization–tandem mass spectrometry (LC‐ESI‐MS/MS). Overall, seven proteins were uniquely identified in the sera of clinically healthy fish, while 27 proteins were unique to the sera of CMS fish. Of the latter, 24 have been associated with cardiac disease in humans. These were grouped as leakage enzymes (creatine kinase, lactate dehydrogenase, glycogen phosphorylase and carbonic anhydrase); host reaction proteins (acute‐phase response proteins—haptoglobin, fibrinogen, α2‐macroglobulin and ceruloplasmin; and complement‐related proteins); and regeneration/remodelling proteins (fibronectin, lumican and retinol). Clinical evaluation of the suitability of these proteins as biomarkers of CMS, either individually or as part of a panel, is a logical next step for the development of early diagnostic tools for CMS.
Spiritual needs among Koreans and Americans with advanced chronic illnesses: A cultural comparison
Authors: Mamier Iris , Kim Sun Min , Petersen Denise , Bae Hye‐Jin , Taylor Elizabeth Johnston , Kang Kyung‐Ah
Published: July 2021

Aims and objectives

This study aimed to measure the frequency of spiritual needs, identify the factors associated with these needs among Korean and American persons living with an advance chronic illness and compare them from a cross‐cultural perspective.

Background

Persons with serious or life‐limiting illnesses often have spiritual needs. Unmet spiritual needs are associated with poor well‐being and threaten psychological health. Little is known about how specific spiritual needs vary across cultures.

Design

A quantitative, cross‐sectional, observational cross‐cultural comparison was undertaken.

Methods

The study has been prepared in accordance with the STROBE guidelines. Convenience sampling was used to recruit participants from outpatient clinics in South Korea and Southern California (N = 202). Spiritual needs were measured using the Spiritual Interests Related to Illness Tool (SpIRIT); demographic and illness‐related variables were also assessed using paper‐and‐pencil questionnaires. Data were analysed using various parametric statistical tests, including multiple regression analysis.

Results

The findings quantify the intensity and types of spiritual needs that persons living with an advanced chronic illness experience. Furthermore, they show how the spiritual needs of religiously diverse samples of South Koreans and Americans differ. The findings also indicate that self‐reported spirituality and religiosity independently explain a substantial amount of the variance in spiritual needs.

Conclusions

In both the samples, spiritual needs were reported and associated with spirituality and religiosity. Although all the eight domains of spiritual needs assessed by the SpIRIT were pertinent to the Korean and American samples, they were prioritised differently.

Relevance to clinical practice

Screening patients to ascertain how important spirituality or religiosity is to them may help clinicians focus their in‐depth assessments on those who report high levels of spirituality or religiosity because these patients may experience the strongest spiritual needs. The SpIRIT shows promise as a measure of diverse spiritual needs.
A clinical‐academic partnership to develop a family management intervention for parents of preterm infants
Authors: Weber Ashley M. , Voos Kristin C. , Bakas Tamilyn M. , Rice Jared B. , Blatz Mary Ann , Ribeiro Ana Paula Duarte , Tubbs‐Cooley Heather L. , Rota Matthew J. , Kaplan Heather C.
Published: July 2021

Aims

To examine the critical role that an academic clinical partnership played in the development and refinement of a family management intervention in the Neonatal Intensive Care Unit (NICU).

Background

Clinical‐academic partnerships enable earlier infusion of implementation science principles into development of evidence‐based interventions, yet partners often report difficulty leveraging resources, personnel and expertise to create beneficial outcomes for all.

Design

Longitudinal qualitative descriptive design.

Methods

To develop and refine the intervention, designated time was taken during meetings of the NICU’s Parent Partnership Council (PPC), a committee comprised of nursing, physician and allied health leadership and former NICU parents. Partnership was also achieved by having bedside clinical nurses, in addition to medical and nursing students, participate as research team members. Qualitative data were collected via email, research team and Council meetings, and informal individual chats with key stakeholders (N = 25) and NICU mothers (N = 22). Qualitative data were analysed deductively using thematic analysis based on MacPhee’s partnership logic model and the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE‐AIM) model. The consolidated criteria for reporting qualitative research checklist guided our work.

Results

During Council meetings, the clinical‐academic nurse, Director of Family‐Integrated Care and Council members identified the need for a family management intervention, and worked together to develop and refine PREEMIE PROGRESS. Mothers found the intervention had numerous strengths and perceived a benefit knowing they helped future parents.

Conclusions

This work was only possible by leveraging both the university’s technology/research resources and the clinical expertise of the NICU staff and PPC. Co‐authored presentations, publications and grant funding continued this NICU’s legacy in family‐centred care and helped shape the clinical‐academic nurse’s career.

Relevance to clinical practice

Clinical‐academic partnerships can promote excellence in nursing practice, research and education through swifter knowledge translation and earlier infusion of implementation science principles into the development of evidence‐based nursing interventions.
Healthcare personnel's working conditions in relation to risk behaviours for organism transmission: A mixed‐methods study
Authors: Arvidsson Lisa , Lindberg Magnus , Skytt Bernice , Lindberg Maria
Published: July 2021

Aims and objectives

To investigate healthcare personnel's working conditions in relation to risk behaviours for organism transmission.

Background

Healthcare personnel's behaviour is often influenced by working conditions that in turn can impact the development of healthcare‐associated infections. Observational studies are scarce, and further understanding of working conditions in relation to behaviour is essential for the benefit of the healthcare personnel and the safety of the patients.

Design

A mixed‐methods convergent design.

Methods

Data were collected during 104 h of observation at eight hospital units. All 79 observed healthcare personnel were interviewed. Structured interviews covering aspects of working conditions were performed with the respective first‐line manager. The qualitative and quantitative data were collected concurrently and given equal priority. Data were analysed separately and then merged. The study follows the GRAMMS guidelines for reporting mixed‐methods research.

Results

Regardless of measurable and perceived working conditions, risk behaviours frequently occurred especially missed hand disinfection. Healthcare personnel described staffing levels, patient‐level workload, physical factors and interruptions as important conditions that influence infection prevention behaviours. The statistical analyses confirmed that interruptions increase the frequency of risk behaviours. Significantly higher frequencies of risk behaviours also occurred in activities where healthcare personnel worked together, which in the interviews was described as a consequence of caring for high‐need patients.

Conclusions

These mixed‐methods findings illustrate that healthcare personnel's perceptions do not always correspond to the observed results since risk behaviours frequently occurred regardless of the observed and perceived working conditions. Facilitating the possibility for healthcare personnel to work undisturbed when needed is essential for their benefit and for patient safety.

Relevance for Clinical Practice

The results can be used to enlighten healthcare personnel and managers and when designing future infection prevention work.
Risk Management in Financial Institutions: A Replication
Authors: GUEST PAUL M.
Published: July 2021

Rampini, Viswanathan, and Vuillemey (RVV) show empirically that net worth drives hedging. I identify discrepancies to which RVV's key findings are not robust: the positive correlation between net worth and hedging is not independent of institution size, house price decline shocks to net worth (which RVV use for identification) have mixed effects on hedging that are not robust across alternative specifications, and the treatment effects on net worth and hedging are not increasing in real estate exposure, inconsistent with a causal explanation. Overall, my analysis does not support the conclusion of RVV that higher net worth causes more hedging.
Screening of genes related to survival prognosis of cervical squamous cell carcinoma and construction of prognosis prediction model
Authors: Qin Rui , Cao Lu , Ye Cong , Wang Junrong , Sun Ziqian
Published: July 2021

Aim

We aimed to screen for the genes related to survival prognosis of cervical squamous cell carcinoma (CSCC) and then constructed a prognosis prediction model.

Methods

The GSE63514 dataset was obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO). The CSCC gene dataset and the GSE44001 dataset were obtained from The Cancer Genome Atlas and NCBI GEO, respectively. The Kaplan–Meier (KM) curve was used to evaluate the association between high and low prognosis that was with the actual survival prognosis information. The Cox proportional hazards model was used to screen out the optimized prognostic‐related signature differentially expressed gene (DEG) combinations. Gene set enrichment analysis was used to perform pathway enrichment annotation analysis for DEGs that were related to risk grouping.

Results

In total, 16 399 DEGs were obtained and 23 gene ontology biological processes and 8 Kyoto Encyclopedia of Genes and Genomes pathways were screened. Nine optimized DEG groups related to independent prognosis were selected. The KM curves of pathologic N0 and N1 showed that low‐risk group were associated with a better overall survival (p = 1.518e; p = 1.704e−01). The pathways related to risk grouping were cytokine–cytokine receptor interaction, JAK stat signaling pathway, and glycolysis–gluconeogenesis.

Conclusion

On the basis of this study, we established a prognostic risk model, which provided a reliable prognostic tool and was of great significance for locating the biomarkers related to survival prognosis in CSCC.
Coagulopathy is not predictive of bleeding in patients with acute decompensation of cirrhosis and acute‐on‐chronic liver failure
Authors: Campello Elena , Zanetto Alberto , Bulato Cristiana , Maggiolo Sara , Spiezia Luca , Russo Francesco Paolo , Gavasso Sabrina , Mazzeo Pierluigi , Tormene Daniela , Burra Patrizia , Angeli Paolo , Senzolo Marco , Simioni Paolo
Published: July 2021

Background & Aims

Understanding factors responsible for the increased bleeding tendency in acute‐on‐chronic liver failure (ACLF) would improve the management of these complications. We investigated coagulation alterations in ACLF and assessed whether they were predictive of bleeding.

Methods

Cirrhosis patients with ACLF (cases) and acute decompensation (AD, controls) were prospectively recruited and underwent an extensive haemostatic assessment including standard tests, pro and anticoagulant factors, thrombomodulin‐modified thrombin generation (TG) and thromboelastometry (ROTEM®). In study part 1 (case‐control), we compared coagulation in ACLF vs AD. In study part 2 (prospective), all patients were followed for bleeding, and predictors of outcome were assessed.

Results

Ninety‐one patients were included (51 with ACLF, 40 with AD). Infections and ascites/renal dysfunction were the most common precipitating and decompensating events. Platelet count was lower while INR and activated partial thrombin time were longer in ACLF cohort vs AD. Regarding clotting factors, fibrinogen and factor VIII were comparable between groups while protein C and antithrombin were significantly reduced in ACLF. Endogenous thrombin potential by TG was comparable between groups. Clotting formation time and clot stability by ROTEM® were significantly lower in ACLF, indicative of a more hypocoagulable state. No haemostasis alteration could discriminate between patients who had bleeding complications during hospitalization and those who did not.

Conclusion

We found coagulation changes in ACLF to largely overlap with that of AD and evidence of preserved coagulation capacity in both groups. ROTEM alterations were indicative of a more pronounced hypocoagulable state in ACLF; however, no correlation was found between such alterations and bleeding.
Peripheral neuropathy after viral eradication with direct‐acting antivirals in chronic HCV hepatitis: A prospective study
Authors: Zanone Maria M. , Marinucci Claudia , Ciancio Alessia , Cocito Dario , Zardo Federica , Spagone Emanuela , Ferrero Bruno , Cerruti Cristina , Charrier Lorena , Cavallo Franco , Saracco Giorgio M. , Porta Massimo
Published: July 2021

Background

HCV‐related extra‐hepatic complications include peripheral neuropathies, with important prevalence and impact. A recent metanalysis of previous intervention trials concluded for insufficient data to support evidence‐based treatments for this complication. In this longitudinal study, we assessed for the first time prevalence and outcome of neuropathy in a cohort of patients with chronic HCV, before and after direct‐acting antiviral agent (DAA) treatment.

Method

Ninety‐four patients (mean age 58.5 ± 9.9, infection duration 22.2 ± 6.3 years) without systemic and metabolic diseases, underwent neurological examination and electroneurography studies before (T0) and 10.4 ± 1.7 months after the end of DAA therapy (T1), and cryoglobulins (CG) assessment. Muscle strength was evaluated by Medical Research Council (MRC) score; neuropathic pain, sensory function, disability, quality of life were assessed by validated questionnaires (DN4, NPSI, SSS, INCAT and Euro‐QoL).

Results

At T0, sensory‐motor neuropathy was detected in 22 patients (23%), reflexes were depressed in 32 (34%) with no association with infection duration, viral load, age, CG. Neuropathic pain (DN4 ≥4) was present in 37 patients (39%). At T1, out of the 22 patients with altered electroneurography, 3 had died or developed HCC, 4 showed normal electroneurography, and nerve amplitude parameters tended to improve in the whole group. Only 11 patients (12%) had depressed reflexes and 10 (11%) DN4 ≥4 (P < .05 compared to T0). Scores for MRC, questionnaires and Euro‐QoL improved significantly (P < .05).

Conclusion

Our study confirms the high prevalence of clinical and subclinical peripheral sensory‐motor neuropathy in patients with HCV infection and indicates improvement after eradication by DAA. These results support the need for larger intervention studies.
Anti‐TNFα treatment in Crohn’s disease: Impact on hepatic steatosis, gut‐derived hormones and metabolic status
Authors: Manka Paul , Sydor Svenja , Wase Nishikant , Best Jan , Brandenburg Malte , Hellbeck Annika , Schänzer Julia , Vilchez‐Vargas Ramiro , Link Alexander , Figge Anja , Jähnert Andreas , von Arnim Ulrike , Coombes Jason D. , Cubero Francisco‐Javier , Kahraman Alisan , Kim Moon‐Sung , Kälsch Julia , Kinner Sonja , Faber Klaas‐Nico , Moshage Han , Gerken Guido , Syn Wing‐Kin , Friedman Scott L. , Canbay Ali , Bechmann Lars P.
Published: July 2021

Background and Aims

An association between Crohn's disease (CD) and hepatic steatosis has been reported. However, the underlying mechanisms of steatosis progression in CD are not clear. Among the most effective CD treatments are agents that inhibit Tumor‐Necrosis‐Factor (TNF) activity, yet it is unclear why anti‐TNFα agents would affect steatosis in CD. Recent studies suggest that microbiome can affect both, CD and steatosis pathogenesis. Therefore, we here analysed a potential relationship between anti‐TNF treatment and hepatic steatosis in CD, focusing on the gut‐liver axis.

Methods

This cross‐sectional study evaluated patients with established CD, with and without anti‐TNFα treatment, analysing serum markers of liver injury, measurement of transient elastography, controlled attenuation parameter (CAP) and MRI for fat detection. Changes in lipid and metabolic profiles were assessed by serum and stool lipidomics and metabolimics. Additionally, we analysed gut microbiota composition and mediators of bile acid (BA) signalling via stool and serum analysis.

Results

Patients on anti‐TNFα treatment had less hepatic steatosis as assessed by CAP and MRI. Serum FGF19 levels were significantly higher in patients on anti‐TNFα therapy and associate with reduced steatosis and increased bowel motility. Neutral lipids including triglycerides were reduced in the serum of patients on anti‐TNF treatment. Bacteria involved in BA metabolism and FGF19 regulation, including Firmicutes, showed group‐specific alterations with low levels in patients without anti‐TNFα treatment. Low abundance of Firmicutes was associated with higher triglyceride levels.

Conclusions

Anti‐TNFα treatment is associated with reduced steatosis, lower triglyceride levels, alterations in FXR‐signalling (eg FGF19) and microbiota composition in CD.
Global incidence, prevalence and features of primary sclerosing cholangitis: A systematic review and meta‐analysis
Authors: Mehta Tej I. , Weissman Simcha , Fung Brian M. , Sotiriadis John , Lindor Keith D. , Tabibian James H.
Published: July 2021

Background & Aims

Primary sclerosing cholangitis (PSC) is an idiopathic, cholestatic liver disease with a diverse range of clinical manifestations. Inter‐regional data on PSC are variable, but its global geoepidemiology has not been well‐studied. We aimed to examine the worldwide incidence, prevalence and features of PSC and PSC‐inflammatory bowel disease (PSC‐IBD).

Methods

A systematic search of multiple databases was conducted to identify all original, full‐text studies until December 2020 with data regarding the incidence rate (IR) and/or prevalence of PSC. Outcomes were PSC IR, prevalence, features and IBD concurrence. Additionally, a meta‐analysis of PSC IR was performed. The study was registered in PROSPERO (CRD42021224550).

Results

Of the 1003 studies identified, 17 studies spanning three continents were included. PSC IR was 0.60 per 100 000 person‐years (PY) (95% confidence interval: 0.37‐0.88 per 100 000 PY). In pooled subgroup analysis for studies conducted in Europe and North America, PSC IR was 0.62 and 0.53 per 100 000 PY, respectively. PSC prevalence ranged 0‐31.7 per 100 000 persons, with notable inter‐regional differences. Mean age at PSC diagnosis was bimodally distributed, with relative peaks at 15 and 35 years. Mean concurrence of IBD with PSC was 50%, with 76% having ulcerative colitis, 17% Crohn's disease and 8% indeterminate/unspecified IBD.

Conclusion

While considerable heterogeneity exists in the geoepidemiology of PSC, overall, the classical dogmata of male predilection, bimodal distribution of mean age and high PSC‐IBD concurrence appear to hold true. Despite a seemingly stable IR over time, further studies are needed to better understand the geoepidemiology of PSC.
The C5 protein encoded by Ageratum leaf curl Sichuan virus is a virulence factor and contributes to the virus infection
Authors: Li Pengbai , Su Feng , Meng Qiyuan , Yu Huabin , Wu Gentu , Li Mingjun , Qing Ling
Published: July 2021

Earlier reports have indicated that begomoviruses encode four proteins (AC1/C1, AC2/C2, AC3/C3, and AC4/C4 proteins) using complementary‐sense DNA as the template. In recent years, several reports have shown that some begomoviruses also encode an AC5/C5 protein from the complementary DNA strand, and these AC5/C5 proteins play different roles in virus infections. Here, we provide evidence showing that Ageratum leaf curl Sichuan virus (ALCScV), a monopartite begomovirus, also encodes a C5 protein that is important for disease symptom formation and can affect viral replication. Infection of Nicotiana benthamiana plants with a potato virus X (PVX)‐based vector carrying the ALCScV C5 gene resulted in more severe disease symptoms and higher virus accumulation levels. ALCScV C5 protein can be found in the cytoplasm and the nucleus. Furthermore, this protein is also a suppressor of posttranscriptional gene silencing. Mutational analysis showed that knockout of C5 gene expression significantly reduced ALCScV‐induced disease symptoms and virus accumulation, while expression of the C5 gene using the PVX‐based vector enhanced ALCScV accumulation in coinfected N. benthamiana plants.
Studying seed dispersal through the lens of movement ecology
Authors: Borah Binod , Beckman Noelle G.
Published: July 2021

Frugivore movement plays a critical role in animal‐mediated seed dispersal. Frugivores utilize resources that are heterogeneously distributed in the landscape and execute complex movement to exploit these resources. Employing the ‘movement ecology paradigm', we discuss the drivers behind frugivore movement, categorize movement into canonical activity modes and explore the potential impacts on seed dispersal effectiveness via removal and deposition of seeds. Among the movement drivers, frugivore physiology determines the goals, motion capacities determine how frugivores move across their heterogenous landscape, navigation capabilities determine how frugivores acquire and process both internal and external information that set them in motion, and biotic interactions further modulate frugivore movement. The movement process that emerges from the interactions of these drivers can be classified into different canonical activity modes that determine levels of seed removal and generate clumped, even or other spatial distributions of seed deposition. We provide a novel framework to integrate movement drivers, frugivore activities and seed dispersal services. We provide future directions utilizing advances in animal movement research to better understand the role of animal movement in the effectiveness of seed dispersal, highlighting potential impacts of increased anthropogenic activities. To advance a mechanistic understanding of animal‐mediated seed dispersal, we encourage increased collaboration between animal movement and plant ecologists.
Association of different enteroviruses with atopy and allergic diseases in early childhood
Authors: Palmu Tiina , Lehtonen Jussi , Korhonen Laura , Virtanen Suvi M. , Niemelä Onni , Toppari Jorma , Ilonen Jorma , Veijola Riitta , Knip Mikael , Laitinen Olli H. , Lönnrot Maria , Hyöty Heikki
Published: July 2021

Background

Enterovirus (EV) infections, being among the most prevalent viruses worldwide, have been associated with reduced risk of allergic diseases. We sought to determine the association between EVs and allergic sensitization and disease in early childhood.

Methods

The study was carried out in a nested case‐control setting within a prospective birth cohort in Finland. We included 138 case children who had specific IgE (s‐IgE) sensitization at the age of 5 years and 138 control children without s‐IgE sensitization. Allergic disease was recorded at study visits and identified with the ISAAC questionnaire. We screened for the presence of serotype‐specific antibodies against 41 EVs at 1–5 years of age and assessed their association with allergic sensitization and disease.

Results

The overall number of EV infections did not differ between s‐IgE–sensitized children and non‐sensitized control children. However, there was a tendency of case children with an allergic disease having less EV infections than their controls. This observation was statistically significant for species A EVs in case children with atopic dermatitis vs. control children: OR 0.6 (95% CI 0.36–0.99), p = .048.

Conclusion

This study supports the evidence that EV exposure and development of allergic disease are inversely associated. Interestingly, the inverse association was not observed for bare atopic IgE sensitization, but for IgE sensitization coupled with clinical atopic disease. This suggests that environmental factors influencing IgE sensitization may differ from those influencing progression to clinical allergic disease.
Propensity Score Analysis for a Semi-Continuous Exposure Variable: A Study of Gestational Alcohol Exposure and Childhood Cognition
Authors: Akkaya Hocagil Tugba , Cook Richard J. , Jacobson Sandra W. , Jacobson Joseph L. , Ryan Louise M.
Published: July 2021

Propensity score methodology has become increasingly popular in recent years as a tool for estimating causal effects in observational studies. Much of the related research has been directed at settings with binary or discrete exposure variables with more recent work involving continuous exposure variables. In environmental epidemiology, a substantial proportion of individuals is often completely unexposed while others may experience heavy exposure leading to an exposure distribution with a point mass at zero and a heavy right tail. We suggest a new approach to handle this type of exposure data by constructing a propensity score based on a two-part model and show how this model can be used to more reliably adjust for covariates of a semi-continuous exposure variable. We also consider the case when a misspecified propensity score is used in a regression adjustment and derive an explicit form of the bias. We show that the potential bias gets smaller as the estimated propensity score gets closer to the true expectation of the exposure variable given a set of observed covariates. While this result pertains to a more general setting, we use it to evaluate the potential bias in settings in which the true exposure has a semi-continuous structure. We also evaluate and compare the performance of our proposed method through simulation studies relative to a simpler linear regression-based propensity score for a continuous exposure variable as well as through direct covariate adjustment. Overall, we find that using a propensity score constructed via a two-part model significantly improves the regression estimate when the exposure variable is semi-continuous in nature. Specifically when the proportion of non-exposed subjects is high and the effects of covariates on exposure and outcome are strong, the proposed two-part propensity score method outperforms the more standard competing methods. We illustrate our method using data from the Detroit Longitudinal Cohort Study in which the exposure variable reflects gestational alcohol exposure featuring zero values and a long tail.
What factors affect patients’ ability to access healthcare? An overview of systematic reviews
Authors: Dawkins Bryony , Renwick Charlotte , Ensor Tim , Shinkins Bethany , Jayne David , Meads David
Published: July 2021

OBJECTIVES

This overview aims to synthesise global evidence on factors affecting healthcare access, and variations across low‐ and middle‐income countries (LMICs) vs. high‐income countries (HICs); to develop understanding of where barriers to healthcare access lie, and in what context, to inform tailored policies aimed at improving access to healthcare for all who need it.

METHODS

An overview of systematic reviews guided by a published protocol was conducted. Medline, Embase, Global Health and Cochrane Systematic Reviews databases were searched for published articles. Additional searches were conducted on the Gates Foundation, WHO and World Bank websites. Study characteristics and findings (barriers and facilitators to healthcare access) were documented and summarised. The methodological quality of included studies was assessed using an adapted version of the AMSTAR 2 tool.

RESULTS

Fifty‐eight articles were included, 23 presenting findings from LMICs and 35 presenting findings from HICs. While many barriers to healthcare access occur in HICs as well as LMICs, the way they are experienced is quite different. In HICs, there is a much greater emphasis on patient experience; as compared to the physical absence of care in LMICs.

CONCLUSIONS

As countries move towards universal healthcare access, evaluation methods that account for health system and wider cultural factors that impact capacity to provide care, healthcare finance systems and the socio‐cultural environment of the setting are required. Consequently, methods employed in HICs may not be appropriate in LMICs due to the stark differences in these areas.