bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease‐modifying agents for multiple sclerosis and the risk for reporting cancer: A disproportionality analysis using the US Food and Drug Administration Adverse Event Reporting System database
Authors: Stamatellos Vasileios‐Periklis , Siafis Spyridon , Papazisis Georgios 
Published: May 2021

AimWhile the efficacy of disease‐modifying therapies (DMTs) for patients with multiple sclerosis (MS) is established, little is known about their long‐term safety. Cancer‐risk after DMT use remains unclear. This study aimed to investigate whether the prescription of DMTs for patients with MS increases the risk of reporting cancer.MethodsData from the Food and Drug Administration Adverse Event Reporting System were extracted from 2004 to 2020. After data cleaning, the crude and adjusted reported odds ratios (cROR and aROR) for cancer were calculated for DMTs with Interferon beta‐1a as the reference drug. Sensitivity analyses investigated the group of reports with multiple registered DMTs, the effect of indication restriction and the results when using the rest of the DMTs as reference.ResultsFor malignant tumours, aROR (95% confidence interval [CI]) values were Cladribine 0.46 (0.18‐0.95), Dimethyl fumarate 0.30 (0.27‐0.34), Fingolimod 0.61 (0.53‐0.70), Glatiramer 0.50 (0.43‐0.58), Alemtuzumab 0.84 (0.64‐1.08), Interferon beta‐1b 0.49 (0.42‐0.56), Natalizumab 0.36 (0.34‐0.39), Ocrelizumab 0.48 (0.29‐0.74), Peginterferon beta‐1a 0.35 (0.26‐0.48), Siponimod 0.89 (0.47‐1.54) and Teriflunomide 0.25(0.21‐0.30) adjusted to age, gender and concomitant medications. In the sensitivity analysis, when the rest of the drugs were used as a reference, Interferon beta‐1a and Peginterferon beta‐1a had aROR (95% CI) 2.60 (2.47‐2.74, P < .001) and Alemtuzumab had aROR 1.47 (1.13‐1.88, I = .003).ConclusionsNo safety signal for increased cancer risk was detected among the approved DMTs. A potential safety signal detected in the sensitivity analysis concerning Interferon beta‐1a and Alemtuzumab requires further evaluation with more robust evidence.
Mediating worklife learning and the digitalisation of work
Authors: Billett Stephen 
Published: May 2021

AbstractCompetence in contemporary working life requirements is increasingly aligned with electronically mediated tasks and work roles: ie, the digitalisation of work. This alignment necessitates workers learning and utilising the conceptual knowledge and ways of working needed for this work. This knowledge is often distinct from and displaces workers' existing ways of knowing, which threatens their competence and sense of self. Yet, it can be difficult to access, learn and practice, requiring it to be mediated through interventions making it knowable. For working age adults, this often needs to occur through work activities for efficacy and practical reasons. These worklife learning issues are discussed here from a cultural psychological perspective, drawing on studies of contemporary work and human cognition, considerations for how these forms of knowledge can be made accessible and their processes of knowledge construction be supported. Four key propositions are advanced: (a) this knowledge needs to be made accessible to be engaged with and learnt; (b) that can often best occur in work settings; (c) workers' occupational subjectivities need accommodating; and (d) electronically mediated forms and artefacts offer means to make that knowledge accessible and support its learning. Hence, learning, work and digitalisation are reciprocally aligned in promoting both the initial and ongoing development of workers' capacities.Practitioner notesWhat is already known about this topic?The knowledge required for work constantly changes.Digitalised work has changed the requirements of much work and many occupations.Conceptual and symbolic knowledge are required for competence in digital kinds of work.Many studies have illustrated the impact of digital technologies across a range of occupations and industry sectors.What this paper adds?An elaboration of how the knowledge to be learnt and ways of knowing have changed in digital work.Considerations of the implications of the changes for worklife learning (lifelong learning).The importance of digitalised artefacts mediating access to this knowledge through symbolic representations.Implications for practice and/or policyWorking age adults need to be able to access the kinds of knowledge required for digitalised work.Worksites and work practice are potentially the optimum circumstances for accessing and learning this knowledge across working life.The ability of this knowledge to be represented symbolically is a key basis for workers ongoing learning of digitalised work requirements.Digital technology offers means for the conceptual representations to be made accessible.
Validation of the IMPEDE VTE score for prediction of venous thromboembolism in multiple myeloma: a retrospective cohort study
Authors: Covut Fahrettin , Ahmed Ramsha , Chawla Sanchit , Ricaurte Frank , Samaras Christy J. , Anwer Faiz , Garcia Alex V. M. , Angelini Dana E. , Mazzoni Sandra , Faiman Beth , Valent Jason , Khouri Jack 
Published: May 2021

SummaryThe IMPEDE VTE score has recently emerged as a novel risk prediction tool for venous thromboembolism (VTE) in multiple myeloma (MM). We retrospectively reviewed 839 patients with newly diagnosed MM between 2010 and 2015 at Cleveland Clinic and included 575 patients in final analysis to validate this score. The c‐statistic of the IMPEDE VTE score to predict VTE within 6 months of treatment start was 0·68 (95% CI: 0·61–0·75). The 6‐month cumulative incidence of VTE was 5·0% (95% CI: 2·1–7·9) in the low risk group, compared to 12·6% (95% CI: 8·9–16·4%) and 24·1% (95% CI: 12·2–36·1) in the intermediate and high risk groups (P < 0·001 for both). In addition, a higher proportion of patients in the VTE cohort had ECOG performance status of ≥2 as compared to the no VTE cohort (33% vs. 16%, P = 0·001). Other MM characteristics such as stage, immunoglobulin subtype, and cytogenetics were not predictors of VTE. In summary, we have validated the IMPEDE VTE score in our patient cohort and our findings suggest that it can be utilized as a VTE risk stratification tool in prospective studies looking into investigating VTE prophylaxis strategies in MM patients.
NLRP3 at the crossroads between immune/inflammatory responses and enteric neuroplastic remodelling in a mouse model of diet‐induced obesity
Authors: Pellegrini Carolina , Fornai Matteo , Benvenuti Laura , Colucci Rocchina , Caputi Valentina , Palazon‐Riquelme Pablo , Giron Maria Cecilia , Nericcio Anna , Garelli Francesca , D'Antongiovanni Vanessa , Segnani Cristina , Ippolito Chiara , Nannipieri Monica , Lopez‐Castejon Gloria , Pelegrin Pablo , Haskó György , Bernardini Nunzia , Blandizzi Corrado , Antonioli Luca 
Published: May 2021

Background and PurposeEnteric neurogenic/inflammation contributes to bowel dysmotility in obesity. We examined the role of NLRP3 in colonic neuromuscular dysfunctions in mice with high‐fat diet (HFD)‐induced obesity.Experimental ApproachWild‐type C57BL/6J and NLRP3‐KO (Nlrp3−/−) mice were fed with HFD or standard diet for 8 weeks. The activation of inflammasome pathways in colonic tissues from obese mice was assessed. The role of NLRP3 in in vivo colonic transit and in vitro tachykininergic contractions and substance P distribution was evaluated. The effect of substance P on NLRP3 signalling was tested in cultured cells.Key ResultsHFD mice displayed increased body and epididymal fat weight, cholesterol levels, plasma resistin levels and plasma and colonic IL‐1β levels, colonic inflammasome adaptor protein apoptosis‐associated speck‐like protein containing caspase‐recruitment domain (ASC) and caspase‐1 mRNA expression and ASC immunopositivity in macrophages. Colonic tachykininergic contractions were enhanced in HFD mice. HFD NLRP3−/− mice developed lower increase in body and epididymal fat weight, cholesterol levels, systemic and bowel inflammation. In HFD Nlrp3−/− mice, the functional alterations of tachykinergic pathways and faecal output were normalized. In THP‐1 cells, substance P promoted IL‐1β release. This effect was inhibited upon incubation with caspase‐1 inhibitor or NK1 antagonist and not observed in ASC−/− cells.Conclusion and ImplicationsIn obesity, NLRP3 regulates an interplay between the shaping of enteric immune/inflammatory responses and the activation of substance P/NK1 pathways underlying the onset of colonic dysmotility. Identifying NLRP3 as a therapeutic target for the treatment of bowel symptoms related to obesity.
Eco‐evolutionary consequences of habitat warming and fragmentation in communities
Authors: Faillace Cara A. , Sentis Arnaud , Montoya José M. 
Published: May 2021

ABSTRACTEco‐evolutionary dynamics can mediate species and community responses to habitat warming and fragmentation, two of the largest threats to biodiversity and ecosystems. The eco‐evolutionary consequences of warming and fragmentation are typically studied independently, hindering our understanding of their simultaneous impacts. Here, we provide a new perspective rooted in trade‐offs among traits for understanding their eco‐evolutionary consequences. On the one hand, temperature influences traits related to metabolism, such as resource acquisition and activity levels. Such traits are also likely to have trade‐offs with other energetically costly traits, like antipredator defences or dispersal. On the other hand, fragmentation can influence a variety of traits (e.g. dispersal) through its effects on the spatial environment experienced by individuals, as well as properties of populations, such as genetic structure. The combined effects of warming and fragmentation on communities should thus reflect their collective impact on traits of individuals and populations, as well as trade‐offs at multiple trophic levels, leading to unexpected dynamics when effects are not additive and when evolutionary responses modulate them. Here, we provide a road map to navigate this complexity. First, we review single‐species responses to warming and fragmentation. Second, we focus on consumer–resource interactions, considering how eco‐evolutionary dynamics can arise in response to warming, fragmentation, and their interaction. Third, we illustrate our perspective with several example scenarios in which trait trade‐offs could result in significant eco‐evolutionary dynamics. Specifically, we consider the possible eco‐evolutionary consequences of (i) evolution in thermal performance of a species involved in a consumer–resource interaction, (ii) ecological or evolutionary changes to encounter and attack rates of consumers, and (iii) changes to top consumer body size in tri‐trophic food chains. In these scenarios, we present a number of novel, sometimes counter‐intuitive, potential outcomes. Some of these expectations contrast with those solely based on ecological dynamics, for example, evolutionary responses in unexpected directions for resource species or unanticipated population declines in top consumers. Finally, we identify several unanswered questions about the conditions most likely to yield strong eco‐evolutionary dynamics, how better to incorporate the role of trade‐offs among traits, and the role of eco‐evolutionary dynamics in governing responses to warming in fragmented communities.
Peer Effects on Early Language Development in Dual Language Learners
Authors: Schmerse Daniel 
Published: May 2021

This study investigated the vocabulary development of children (N = 547) from linguistically and socioeconomically diverse classrooms in Germany from age 3 in preschool to age 7 in Grade 1. The results showed that for dual language learners (DLLs,n = 107) growth rates in their German majority language skills varied over classrooms. Compared to monolingual children, DLLs improved faster in classrooms with higher peer‐level skills in the majority language than DLLs in classrooms with lower peer‐level skills (controlling for socioeconomic status and classroom quality). DLLs showed stronger growth dynamics than monolingual children during later preschool stages. The findings highlight the role of preschool peers in DLLs’ acquisition of the majority language before entering elementary school.
Intranasal delivery of allergen in a nanoemulsion adjuvant inhibits allergen‐specific reactions in mouse models of allergic airway disease
Authors: Baker James R. , Rasky Andrew J. , Landers Jeffrey J. , Janczak Katarzyna W. , Totten Tiffanie D. , Lukacs Nicholas W. , O’Konek Jessica J. 
Published: May 2021

AbstractBackgroundAtopic diseases are an increasing problem that involve both immediate hypersensitivity reactions mediated by IgE and unique cellular inflammation. Many forms of specific immunotherapy involve the administration of allergen to suppress allergic immune responses but are focused on IgE‐mediated reactions. In contrast, the effect of allergen‐specific immunotherapy on allergic inflammation is complex, not entirely consistent and not well understood. We have previously demonstrated the ability of allergen administered in a nanoemulsion (NE) mucosal adjuvant to suppress IgE‐mediated allergic responses and protect from allergen challenge in murine food allergy models. This activity was associated with decreases in allergen‐specific IL‐10 and reductions in allergic cytokines and increases in regulatory T cells.ObjectiveHere, we extend these studies to using 2 distinct models, the ovalbumin (OVA) and cockroach (CRA) models of allergic airway disease, which are based predominantly on allergic inflammation.MethodsAcute or chronic allergic airway disease was induced in mice using ovalbumin and cockroach allergen models. Mice received three therapeutic immunizations with allergen in NE, and reactivity to airway challenge was determined.ResultsTherapeutic immunization with cockroach or OVA allergen in NE markedly reduced pathology after airway challenge. The 2 models demonstrated protection from allergen challenge‐induced pathology that was associated with suppression of Th2‐polarized immune responses in the lung. In addition, the reduction in ILC2 numbers in the lungs of allergic mice along with reduction in epithelial cell alarmins, IL‐25 and IL‐33, suggests an overall change in the lung immune environment induced by the NE immunization protocol.Conclusions and Clinical RelevanceThese results demonstrate that suppression of allergic airway inflammation and bronchial hyper‐reactivity can be achieved using allergen‐specific immunotherapy without significant reductions in allergen‐specific IgE and suggest that ILC2 cells may be critical targets for this activity.
Comparative incidence and outcomes of COVID‐19 in kidney or kidney‐pancreas transplant recipients versus kidney or kidney‐pancreas waitlisted patients: A single‐center study
Authors: Santos Carlos A. Q. , Rhee Yoona , Hollinger Edward F. , Olaitan Oyedolamu K. , Schadde Erik , Peev Vasil , Saltzberg Samuel N. , Hertl Martin 
Published: May 2021

AbstractBackgroundCOVID‐19 epidemiologic studies comparing immunosuppressed and immunocompetent patients may provide insight into the impact of immunosuppressants on outcomes.MethodsIn this retrospective cohort study, we assembled kidney or kidney‐pancreas transplant recipients who underwent transplant from January 1, 2010, to June 30, 2020, and kidney or kidney‐pancreas waitlisted patients who were ever on the waitlist from January 1, 2019, to June 30, 2020. We identified laboratory‐confirmed COVID‐19 until January 31, 2021, and tracked its outcomes by leveraging informatics infrastructure developed for an outcomes research network.ResultsCOVID‐19 was identified in 62 of 887 kidney or kidney‐pancreas transplant recipients and 20 of 434 kidney or kidney‐pancreas waitlisted patients (7.0% vs. 4.6%, p = .092). Of these patients with COVID‐19, hospitalization occurred in 48 of 62 transplant recipients and 8 of 20 waitlisted patients (77% vs. 40%, p = .002); intensive care unit admission occurred in 18 of 62 transplant recipients and 2 of 20 waitlisted patients (29% vs. 10%, p = .085); and 7 transplant recipients were mechanically ventilated and died, whereas no waitlisted patients were mechanically ventilated or died (11% vs. 0%, p = .116).ConclusionsOur study provides single‐center data and an informatics approach that can be used to inform the design of multicenter studies.
Trauma trends during COVID‐19 alcohol prohibition at a South African regional hospital
Authors: Chu Kathryn M. , Marco Jenna‐Lee , Owolabi Eyitayo Omolara , Duvenage Riaan , Londani Mukhethwa , Lombard Carl , Parry Charles D. H. 
Published: May 2021

AbstractIntroductionThe objective of this study was to examine the relationship between trauma volume and alcohol prohibition during the COVID‐19 lockdown in South Africa.MethodsThis was a retrospective analysis of trauma volume from Worcester Regional Hospital in South Africa from 1 January to 28 December 2020. We compared total volume and incidence rates during five calendar periods; one when alcohol sales were allowed as per normal and four when alcohol sales were completely or partially banned. Poisson regression was used to model differences between alcohol ban and non‐ban periods.ResultsDuring the first period (pre‐COVID‐19, no ban), the trauma admission rate was 95 per 100 days, compared to 39 during the second period (complete ban 1), 74 during the third period (partial ban 1), 40 during the fourth period (complete ban 2) and 105 during the fifth period (partial ban 2). There was a 59–69% decrease in trauma volume between the no ban and complete ban 1 periods. When alcohol sales were partially reinstated, trauma volume significantly increased by 83–90% then dropped again by 39–46% with complete ban 2. By the second half of 2020, when alcohol sales were partially allowed again (partial ban 2), trauma volume increased by 163–250%, thus returning to pre‐COVID‐19 levels.Discussion and ConclusionsOur study demonstrates a clear trend of decreased trauma volume during periods of complete alcohol prohibition compared to non‐ and partial alcohol bans. This finding suggests that temporary alcohol bans can be used to decrease health facility traffic during national emergencies.
How to take an ant’s pulse: a procedure for non‐destructively monitoring baseline and stimulated heart rate in Formicidae
Authors: Davis Andrew K. , Clancy Kathleen Mei , Sasaki Takao 
Published: May 2021

AbstractAnts, like other insects, have a heart that pumps hemolymph rhythmically. We designed an apparatus and procedure to non‐destructively monitor the rate of cardiac contractions in ants, using a modified light microscope and infrared light. This allowed us to obtain the first baseline heart rate data on three ant species, collected in Georgia, USA. We next describe how ant heart rates can be stimulated, for comparing cardiac reactions among colonies, or for assessing stress responses. The procedures described here may be useful for other researchers interested in ant physiology.
Using mobile brain/body imaging to advance research in arts, health, and related therapeutics
Authors: King Juliet L. , Parada Francisco J. 
Published: May 2021

AbstractThe uses of mobile brain/body imaging (MoBI) are expanding and allow for more direct study of the neurophysiological signals associated with behavior in psychotherapeutic encounters. Neuroaesthetics is concerned with the cognitive and neural basis of art appreciation, and scientific correlations are being made in the field that might help to clarify theories claimed in the creative arts therapies. Yet, most neuroaesthetics studies are confined to the laboratory and do not propose a translation for research methods and clinical applications. The creative arts therapies have a long history of clinical success with various patient populations and will benefit from increased scientific explanation to support intervention strategies. Examining the brain dynamics and motor behaviors that are associated with the higher complex processes involved in artistic expression offers MoBI as a promising instrumentation to move forward in linking ideas from neuroaesthetics to the creative arts therapies. Tracking brain dynamics in association with behavioral change allows for more objective and quantitative physiological monitors to evaluate, and together with subjective patient reports provides insight into the psychological mechanisms of change in treatment. We outline a framework that shows how MoBI can be used to study the effectiveness of creative arts therapy interventions motivated by the 4E approach to cognition with a focus on visual art therapy. The article illuminates how a new partnership among the fields of art therapy, neuroscience, and neuroaesthetics might work together within the 4E/MoBI framework in efforts to advance transdisciplinary research for clinical health populations.
Myostatin as a fibroblast‐activating factor impacts on postoperative outcome in patients with hepatocellular carcinoma
Authors: Yoshio Sachiyo , Shimagaki Tomonari , Hashida Ryuki , Kawaguchi Takumi , Tsutsui Yuriko , Sakamoto Yuzuru , Yoshida Yuichi , Kawai Hironari , Yoshikawa Shiori , Yamazoe Taiji , Mori Taizo , Osawa Yosuke , Itoh Shinji , Fukai Moto , Yoshizumi Tomoharu , Taketomi Akinobu , Mori Masaki , Kanto Tatsuya 
Published: May 2021

AbstractAimIn patients with liver cirrhosis, high levels of serum myostatin are associated with poor prognosis. We aimed to clarify the influence of myostatin on the prognosis of patients with non‐alcoholic fatty liver disease–hepatocellular carcinoma (NAFLD‐HCC) without cirrhosis and on the progression of liver fibrosis.MethodsSerum myostatin levels were evaluated in 234 patients who underwent primary surgical resection for single HCC. To clarify the impact of myostatin on liver fibrosis, we established human primary liver fibroblasts from resected livers, and cultured them in the presence of myostatin.ResultsThe median age was 67.4 years, the median L3 skeletal muscle mass index was 44.4 cm2/m2, and the median body mass index was 23.4 kg/m2. Eighty‐two (35.0%) patients had sarcopenia (L3 skeletal muscle mass index: men <42, women <38 cm2/m2). The etiologies of liver disease were hepatitis B virus (n = 61), hepatitis C virus (n = 86), and non‐B non‐C hepatitis (n = 87) including NAFLD (n = 74). High preoperative serum myostatin and vascular invasion were independent predictors of poor overall survival (OS). High serum myostatin was associated with poor OS in patients with no sarcopenia (n = 152). In patients without advanced liver fibrosis (Fibrosis stage, 0–2; n = 58), high levels of serum myostatin were also associated with poor OS, regardless of sarcopenia. Serum myostatin levels were increased with the progression of liver fibrosis. Liver fibroblasts were activated and produced collagen following stimulation with myostatin.ConclusionsIn patients with NAFLD‐HCC without advanced liver fibrosis, high levels of serum myostatin were associated with poor OS. Myostatin activated primary fibroblasts and stimulated collagen production.