bluuebunny/crossref_metadata_2025 huggingface dataset:
Promising targets for therapy of osteoarthritis: a review on the Wnt and TGF-β signalling pathways
Authors: Cherifi Chahrazad , Monteagudo Silvia , Lories Rik J.
Published: April 2021

Osteoarthritis (OA) is the most common chronic joint disorder worldwide, with a high personal burden for the patients and an important socio-economic impact. Current therapies are largely limited to pain management and rehabilitation and exercise strategies. For advanced cases, joint replacement surgery may be the only option. Hence, there is an enormous need for the development of effective and safe disease-modifying anti-OA drugs. A strong focus in OA research has been on the identification and role of molecular signalling pathways that contribute to the balance between anabolism and catabolism in the articular cartilage. In this context, most insights have been gained in understanding the roles of the transforming growth factor-beta (TGF-β) and the Wingless-type (Wnt) signalling cascades. The emerging picture demonstrates a high degree of complexity with context-dependent events. TGF-β appears to protect cartilage under healthy conditions, but shifts in its receptor use and subsequent downstream signalling may be deleterious in aged individuals or in damaged cartilage. Likewise, low levels of Wnt activity appear important to sustain chondrocyte viability but excessive activation is associated with progressive joint damage. Emerging clinical data suggest some potential for the use of sprifermin, a recombinant forms of fibroblast growth factor 18, a distant TGF-β superfamily member, and for lorecivivint, a Wnt pathway modulator.
Return-to-Play Outcomes in Elite Athletes After Cervical Spine Surgery: A Systematic Review
Authors: Leider Joseph , Piche Joshua David , Khan Moin , Aleem Ilyas
Published: April 2021

Context:

Return-to-play (RTP) outcomes in elite athletes after cervical spine surgery are currently unknown.

Objective:

To systematically review RTP outcomes in elite athletes after anterior cervical discectomy and fusion (ACDF), cervical disc replacement (CDR), or posterior foraminotomy (PF) surgery.

Data Sources:

EMBASE, PubMed, Cochrane, and Medline databases from inception until April 2020. Keywords included elite athletes, return to play, ACDF, foraminotomy, and cervical disc replacement.

Study Selection:

Eligible studies included those that reported RTP outcomes in elite athletes after cervical spine surgery.

Study Design:

Systematic review.

Level of Evidence:

Level 4.

Data Extraction:

Data were extracted by 2 independent reviewers.

Results:

The primary outcomes of interest were rates and timing of RTP. Secondary outcomes included performance on RTP. A total of 1720 studies were initially screened. After inclusion criteria were applied, 13 studies with a total of 349 patients were included. A total of 262 (75%) played football, 37 (11%) played baseball, 19 (5%) played rugby, 10 (3%) played basketball, 10 (3%) played hockey, 9 (3%) were wresters, and 2 (1%) played soccer. ACDF was reported in 13 studies, PF in 3 studies, and CDR in 2 studies. The majority of studies suggest that RTP after surgical management is safe in elite athletes who are asymptomatic after their procedure and may lead to higher rates and earlier times of RTP. There is limited evidence regarding RTP or outcomes after CDR or multilevel surgery.

Conclusion:

The management and RTP in elite athletes after cervical spine injury is a highly complex and multifactorial topic. The overall evidence in this review suggests that RTP in asymptomatic athletes after both ACDF and PF is safe, and there is little evidence for decreased performance postoperatively. Surgical management results in a higher RTP rate compared with athletes managed conservatively.
The Salience of Children Increases Adult Prosocial Values
Authors: Wolf Lukas J. , Thorne Sapphira R. , Iosifyan Marina , Foad Colin , Taylor Samuel , Costin Vlad , Karremans Johan C. , Haddock Geoffrey , Maio Gregory R.
Published: April 2021

Organizations often put children front and center in campaigns to elicit interest and support for prosocial causes. Such initiatives raise a key theoretical and applied question that has yet to be addressed directly: Does the salience of children increase prosocial motivation and behavior in adults? We present findings aggregated across eight experiments involving 2,054 adult participants: Prosocial values became more important after completing tasks that made children salient compared to tasks that made adults (or a mundane event) salient or compared to a no-task baseline. An additional field study showed that adults were more likely to donate money to a child-unrelated cause when children were more salient on a shopping street. The findings suggest broad, reliable interconnections between human mental representations of children and prosocial motives, as the child salience effect was not moderated by participants’ gender, age, attitudes, or contact with children.
Improving the effectiveness of a paediatric handbook for new house officers
Authors: Wee Justin Liang Yi , Ting Chun Yi , Cheng Duo-Tong , Kan Sheau Yun , Kang Zhi Lin , Loo Benny Kai Guo
Published: April 2021

Background and objectives:

To help house officers adjust quickly to their new responsibilities, a departmental handbook is provided. As this had not been updated recently and was underutilised, a quality improvement project was undertaken to improve this resource.

Methods:

The handbook was updated and new material added based on feedback from house officers and senior medical staff. Subsequently, house officers were surveyed on their utilization rate of the new handbook and its usefulness in various clinical scenarios. An open-book clinical quiz was administered to gauge their clinical competency.

Results:

There was a 26.8% increase in the proportion of house officers who used the handbook more than once every 2–3 days compared to pre-intervention. There was a significant improvement in quiz scores from 26.7/40 to 31.1/40 between the pre-intervention ( n=19) and post-intervention ( n=37) groups ( p<0.001), as well as perceived usefulness of the handbook in various clinical scenarios as measured on a 10-point Likert scale.

Conclusions:

We find that improvement in the quality of a handbook for paediatric house officers is associated with increase in its utilization and benefits to their clinical competency and confidence level, especially on call. To increase the utilization rate of the handbook, both the user interface and content need to be improved.
Rethinking time in response to the Anthropocene: From timescales to timescapes
Authors: Bensaude-Vincent Bernadette
Published: April 2021

Since the coinage of the term Anthropocene, scholarly debates have been dominated by critics of the reference to anthropos, the abstract undifferentiated global subject of the new geological epoch. Many humanities scholars objected that this aggregated whole obfuscates inequalities and responsibilities. While the prefix ‘Anthropos’ has been the target of sharp criticisms, the suffix ‘cene’ remained unchallenged. This paper questions the relevance of the chronological timeline divided up into a sequence of epochs differentiated in terms of scales. I argue that the discourse about the ‘great acceleration’ pointing to a clash of tempos relies on the chronological framework. The single uniform timeline covering all events from the origin of the universe to the birth of individual people tends to conceal the variety of timelines whose interplay determines the climate. I suggest that the current ecological crisis calls for a radical revision of our notion of time which is based on the western metaphysics where human subjects reign supreme over nature and the earth. This crisis invites us to adopt a polychronic view, assuming a variety of heterogeneous temporal trajectories. The first section presents the thesis of ‘the great acceleration’ as a grand narrative based on on the western modern framework. The second section disentangles the prerequisites of the construction of this universal timeline: the assumption of a view from nowhere that makes all times commensurable. In the third section I venture the metaphor of timescape as an alternative to the usual timescales of the universal chronology. This notion seems more appropriate to understand the ecological crisis as resulting from conflicting temporalities. The final section tests the timescaping approach on the cases of two technologies that are considered as candidate markers of the onset of the Anthropocene: nuclear technology and plastics.
The potential of transformative video design for improving caregiver’s wellbeing
Authors: Petrovic Milica , Gaggioli Andrea
Published: April 2021

The existing interventions for informal caregivers assist with managing health outcomes of the role burden. However, the deeper meaning-making needs of informal caregivers have been generally neglected. This paper reflects on the meaning-making needs of informal caregivers, through the theory of narrative identity, and proposes a new approach – the Transformative Video Design technique delivered via video storytelling. Transformative Video Design assists informal caregivers to re-create a cohesive caregiving story and incorporate it into the narrative identity. The technique is used as a stimulus for triggering the self-re-structure within the narrative identity and facilitating role transformation.
A review on the production, structure, bioactivities and applications of Tremella polysaccharides
Authors: Ma Xia , Yang Meng , He Yan , Zhai Chuntao , Li Chengliang
Published: April 2021

Tremella polysaccharide is known to be structurally unique and biologically active natural products, abundant and versatile in activities and applications in food industry, daily chemical industry and medicine industry. In order to improve the industrialisation of Tremella polysaccharide, the limitations of preparation and structure-activity relationship of Tremella polysaccharide were reviewed in this paper. The research progress of Tremella polysaccharide in the past 20 years was summarized from the sources, preparation methods, molecular structure, activity and application, and the research trend in the future was also prospected. The application prospect of Tremella polysaccharide in against multiple sub-health states was worth expecting.
Rapid, remote and responsive research during COVID-19
Authors: Richardson Jane , Godfrey Barry , Walklate Sandra
Published: April 2021

In March 2020, the UK Research and Innovation announced an emergency call for research to inform policy and practice responses to the COVID-19 pandemic. This call implicitly and explicitly required researchers to work rapidly, remotely and responsively. In this article, we briefly review how rapid response methods developed in health research can be used in other social science fields. After outlining the literature in this area, we use the early stages of our applied research into criminal justice responses to domestic abuse during COVID-19 as a case study to illustrate some of the practical challenges we faced in responding to this rapid funding call. We review our use of and experience with remote research methods and describe how we used and adapted these methods in our research, from data gathering through to transcription and analysis. We reflect on our experiences to date of what it means to be responsive in fast-changing research situations. Finally, we make some practical recommendations for conducting applied research in a ‘nimble’ way to meet the demands of working rapidly, remotely, responsively and, most importantly, responsibly.
Metadiscourse and Voice Construction in Discussion Sections in BA Theses by Chinese University Students Majoring in English
Authors: Peng Jian-E , Zheng Yuting
Published: April 2021

Voice is considered essential in academic writing, and metadiscourse is an important device contributing to voice. This study explores the use of metadiscourse and voice construction in Bachelor of Arts (BA) theses written at the onset and final stages by university undergraduates majoring in English in China. A corpus consisting of the discussion sections in the first and final versions of 35 BA theses was built, annotated, and analyzed. Two academics from this university were then invited to evaluate 10 pairs of the texts and specify textual elements that conveyed voice and to provide further comments in a follow-up interview. Results showed that the students used significantly more evidentials, hedges, and boosters in the final versions. The reviewers perceived minor growth in voice strength from the sample texts, and they commented that both content-related features and metadiscourse contributed to voice. This study highlights the importance of cultivating undergraduates’ awareness of voice construction and the use of metadiscourse in academic writing.
Societal transformation: Eastern European experience and conceptualization
Authors: Genov Nikolai
Published: April 2021

The paper contains analyses of attempts at explaining the profound changes in Eastern Europe after 1989. The analyses are guided by the conceptual framework of social interaction. It covers the micro, meso and macro level of the social organization. The first target is the theory of transition. The diagnosis reveals some constructive features of the theory together with its difficulties to get operationalized and effectively used in explanations. The major deficit of the theory is the absence of a concept of society. Based on the concept of social interaction the conceptual framework of societal transformation efficiently functions as a heuristic tool and as an organizer of knowledge. Is the societal transformations conceptual framework sufficient for a full-fledged explanation of the reform processes in Eastern Europe? The search for an answer leads to increasing relevance of the region’s involvement in the globalization. The conclusion is that the impact of global trends should be integrated in the explanatory procedures of the continuing transformation of Eastern European societies.
A Quantifiable Risk Factor for ACL Injury: Applied Mathematics to Model the Posterolateral Tibial Plateau Surface Geometry
Authors: Tat Jimmy , Crapser Drew , Alaqeel Motaz , Schupbach Justin , Lee-Howes Jacob , Tamimi Iskandar , Burman Mark , Martineau Paul A.
Published: April 2021

Background:

The mechanism for traumatic ruptures of the native anterior cruciate ligament (ACL) is frequently a noncontact injury involving a valgus moment with internal rotation of the tibia. The abnormal rotation and translation of the lateral femoral condyle posteroinferiorly relative to the lateral tibial plateau is thought to be related to the geometry of the tibial plateau.

Purpose/Hypothesis:

The purpose of the study was to mathematically model the posterior tibial plateau geometry in patients with ACL injuries and compare it with that of matched controls. The hypothesis was that increased convexity and steepness of the posterior aspect of the lateral plateau would subject knees to higher forces, leading to a potentially higher risk of ACL injury.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

We mathematically modeled the posterior curvature of the lateral tibial plateau in 64 patients with ACL injuries and 68 matched controls. Using sagittal magnetic resonance imaging scans of the knee, points on the articular cartilage of the posterolateral tibial plateau were selected and curve-fitted to a power function ( y = a × xn). For coefficient a and coefficient n, both variables modulated the shape of the curve, where a larger magnitude represented an increase in slope steepness. Groups were compared using a Mann-Whitney test and α < .05.

Results:

There was a significant difference in surface geometry between the patients with ACL injuries and matched controls. The equation coefficients were significantly larger in the patients with ACL injuries: coefficient a (ACL injury, 0.9 vs control, 0.68; P < .0001) and coefficient n (ACL injury, 0.34 vs control, 0.30; P = .07). For coefficient a, there was a 78.9% sensitivity, 77.5% specificity, and odds ratio of 12.6 (95% CI, 5.5-29.0) for ACL injury using a cutoff coefficient a = .78.

Conclusion:

Patients with ACL injuries had a significantly greater posterolateral plateau slope. The steeper drop off may play a role in higher anterior translation forces, coupled with internal rotation torques on the knee in noncontact injury, which could increase ACL strain and predispose to ACL injury.
Racial Resentment, Empathy, and Support for Release during COVID-19: Results from a Survey Experiment
Authors: Ivanov Stefan , Novisky Meghan A. , Vogel Matt
Published: April 2021

Coronavirus disease 2019 (COVID-19) has presented the American criminal justice system with unprecedented challenges, including protecting the safety of incarcerated men and women. Given the ill-suited structure of correctional facilities to facilitate health and safety guidelines, one solution is decarceration. Yet decarceration has faced political and public backlash. As no evidence currently exists on how the public views this emergency solution, the authors examined the correlates of support for decarceration by conducting a survey experiment in which respondents were randomly presented with information on the dangers of COVID-19 in prisons and jails. Respondents’ attitudes toward releasing various subgroups of the incarcerated population were then measured. The findings indicate that learning about the health risks of COVID-19 in correctional facilities had no discernable effect on support for decarceration for any subgroup. Racial resentment consistently predicted opposition to release for all groups, although its effect largely operated through empathetic identification with those who commit crimes.
Decline in Rate of Divorce and Separation Filings in Denmark in 2020 Compared with Previous Years
Authors: Fallesen Peter
Published: April 2021

The radical changes to everyday life brought on by the coronavirus disease 2019 (COVID-19) pandemic and the closure of nonfamily social spheres in particular may have impacted marriage dynamics. The author provides evidence on the monthly rates of initiation of divorce and separation filings in Denmark for the period from 2016 to 2020 to examine how filing behavior changed during 2020 compared with the four previous years. Because filing precedes divorce, rates reflect more precisely the temporal dynamic of divorce initiation. Rates of initiation of divorce filings declined in 2020 to the lowest level across the period from 2016 to 2020. On average, monthly rates in 2020 were 7 percent lower than 2019 rates and 20 percent lower than 2016 rates. There is little indication that the COVID-19 pandemic had an immediate influence on divorce dynamics, although the filing rate was more depressed during lockdown periods.
Bright and Dark Spots in Project Studies: Continuing Efforts to Advance Theory Development and Debate
Authors: Geraldi Joana , Söderlund Jonas , Marrewijk Alfons van
Published: April 2021

In this special issue, we encouraged project scholars to be bold and construct their voices. We now reflect on the results, which include the bright spots in four areas: project organizing (organizing and collaborating in and between projects), project value (organizing value in and through projects), project citizenship (living in and through projects), and project scholarship (reflecting on project theorizing and scholarship). We then dared to voice our views on three dark spots: a lack of diversity in the project scholars’ ethnicities, geographies, and genders; in disciplines that extend beyond management and organization studies; and in modes of reflexivity.
Respiratory muscle imaging by ultrasound and MRI in neuromuscular disorders
Authors: van Doorn Jeroen L.M. , Pennati Francesca , Hansen Hendrik H.G. , van Engelen Baziel G.M. , Aliverti Andrea , Doorduin Jonne
Published: April 2021

Respiratory muscle weakness is common in neuromuscular disorders (NMDs) and leads to significant respiratory difficulties. Therefore, reliable and easy assessment of respiratory muscle structure and function in NMDs is crucial. In the last decade, ultrasound and magnetic resonance imaging (MRI) have emerged as promising imaging techniques to assess respiratory muscle structure and function. Respiratory muscle imaging directly measures the respiratory muscles and, in contrast to pulmonary function testing, is independent of patient effort. This makes respiratory muscle imaging suitable to use as a tool in clinical respiratory management and as an outcome parameter in upcoming drug trials for NMDs, particularly in children. In this narrative review, we discuss the latest studies and technological developments in imaging of the respiratory muscles by ultrasound and MRI, and its clinical application and limitations. We aim to increase understanding of respiratory muscle imaging and facilitate its use as an outcome measure in daily practice and clinical trials.
Impact of obstructive sleep apnoea and intermittent hypoxia on blood rheology: a translational study
Authors: Waltz Xavier , Beaudin Andrew E. , Belaidi Elise , Raneri Jill , Pépin Jean-Louis , Pialoux Vincent , Hanly Patrick J. , Verges Samuel , Poulin Marc J.
Published: April 2021

Background

Haemorheological alterations are reported in obstructive sleep apnoea (OSA) and reversed with continuous positive airway pressure (CPAP), observations potentially explained by intermittent hypoxia (IH)-induced oxidative stress. Our objective was to investigate whether IH causes haemorheological alterationsviaoxidative stress.

Methods

Wistar rats were exposed to normoxia (n=7) or IH (n=8) for 14 days. 23 moderate-to-severe OSA patients were assessed at three time-points: baseline, after randomisation to either 2 weeks of nocturnal oxygen (n=13) or no treatment (n=10) and after 1 month of CPAP treatment (n=17). Furthermore, an OSA-free control group (n=13) was assessed at baseline and after time-matched follow-up. We measured haemorheological parameters (haematocrit, blood viscosity, plasma viscosity (rats only), erythrocyte aggregation and deformability (humans only)) and redox balance (superoxide dismutase (SOD), glutathione peroxidase, protein oxidation (advanced oxidation protein products (AOPPs)) and lipid peroxidation (malondialdehyde)). We also tested the haemorheological sensitivity of erythrocytes to reactive oxygen species (ROS) in our human participants using the oxidantt-butyl hydroperoxide (TBHP).

Results

In rats, IH increased blood viscosity by increasing haematocrit without altering the haemorheological properties of erythrocytes. IH also reduced SOD activity and increased AOPPs. In humans, baseline haemorheological properties were similar between patients and control participants, and properties were unaltered following oxygen and CPAP, except erythrocyte deformability was reduced following oxygen therapy. Redox balance was comparable between patients and control participants. At baseline, TBHP induced a greater reduction of erythrocyte deformability in patients while CPAP reduced TBHP-induced increase in aggregation strength.

Conclusions

IH and OSAper sedo not cause haemorheological alterations despite the presence of oxidative stress or higher sensitivity to ROS, respectively.
Association between the renin–angiotensin system and chronic lung allograft dysfunction
Authors: Berra Gregory , Farkona Sofia , Mohammed-Ali Zahraa , Kotlyar Max , Levy Liran , Clotet-Freixas Sergi , Ly Phillip , Renaud-Picard Benjamin , Zehong Guan , Daigneault Tina , Duong Allen , Batruch Ihor , Jurisica Igor , Konvalinka Ana , Martinu Tereza
Published: April 2021

Chronic lung allograft dysfunction (CLAD) is the major cause of death after lung transplantation. Angiotensin II (AngII), the main effector of the renin–angiotensin system, elicits fibrosis in both kidney and lung. We identified six AngII-regulated proteins (Ras homolog family member B (RHOB), bone marrow stromal cell antigen 1 (BST1), lysophospholipase 1 (LYPA1), glutamine synthetase (GLNA), thrombospondin 1 (TSP1) and laminin subunit β2 (LAMB2)) that were increased in urine of patients with kidney allograft fibrosis. We hypothesised that the renin–angiotensin system is active in CLAD and that AngII-regulated proteins are increased in bronchoalveolar lavage fluid (BAL) of CLAD patients.

We performed immunostaining of AngII receptors (AGTR1 and AGTR2), TSP1 and GLNA in 10 CLAD lungs and five controls. Using mass spectrometry, we quantified peptides corresponding to AngII-regulated proteins in BAL of 40 lung transplant recipients (stable, acute lung allograft dysfunction (ALAD) and CLAD). Machine learning algorithms were developed to predict CLAD based on BAL peptide concentrations.

Immunostaining demonstrated significantly more AGTR1+cells in CLADversuscontrol lungs (p=0.02). TSP1 and GLNA immunostaining positively correlated with the degree of lung fibrosis (R2=0.42 and 0.57, respectively). In BAL, we noted a trend towards higher concentrations of AngII-regulated peptides in patients with CLAD at the time of bronchoscopy, and significantly higher concentrations of BST1, GLNA and RHOB peptides in patients that developed CLAD at follow-up (p<0.05). The support vector machine classifier discriminated CLAD from stable and ALAD patients at the time of bronchoscopy (area under the curve (AUC) 0.86) and accurately predicted subsequent CLAD development (AUC 0.97).

Proteins involved in the renin–angiotensin system are increased in CLAD lungs and BAL. AngII-regulated peptides measured in BAL may accurately identify patients with CLAD and predict subsequent CLAD development.
The coexistence of asthma and COPD: risk factors, clinical history and lung function trajectories
Authors: Marcon Alessandro , Locatelli Francesca , Dharmage Shyamali C. , Svanes Cecilie , Heinrich Joachim , Leynaert Bénédicte , Burney Peter , Corsico Angelo , Caliskan Gulser , Calciano Lucia , Gislason Thorarinn , Janson Christer , Jarvis Deborah , Jõgi Rain , Lytras Theodore , Malinovschi Andrei , Probst-Hensch Nicole , Toren Kjell , Casas Lidia , Verlato Giuseppe , Garcia-Aymerich Judith , Accordini Simone
Published: April 2021

Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden.

Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477).

Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991–1993, 1999–2002 and 2010–2013. Disease status was classified in 2010–2013, when the subjects were aged 40–68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV1/FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated.

Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life.

The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood.
Efficacy and safety of fremanezumab in patients with migraine and inadequate response to prior preventive treatment: subgroup analyses by country of a randomized, placebo-controlled trial
Authors: Spierings Egilius L. H. , Kärppä Mikko , Ning Xiaoping , Cohen Joshua M. , Campos Verena Ramirez , Yang Ronghua , Reuter Uwe
Published: April 2021

Background

The FOCUS study evaluated the efficacy of migraine preventive medications across different countries within the same patient population, particularly for patients with difficult-to-treat migraine. These prespecified subgroup analyses evaluated efficacy by country in the FOCUS study of fremanezumab in adults with episodic migraine or chronic migraine and documented inadequate response to 2 to 4 migraine preventive medication classes.

Methods

Overall, 838 participants were enrolled in the FOCUS study, a randomized, double-blind, placebo-controlled, parallel-group, phase 3b study performed at 104 sites. For 12 weeks of double-blind treatment, patients were randomized (1:1:1) to quarterly fremanezumab, monthly fremanezumab, or matched placebo. The primary efficacy endpoint was the mean change from baseline in monthly average migraine days over 12 weeks of double-blind treatment, evaluated by country in these subgroup analyses.

Results

Of 14 countries contributing data, the Czech Republic (n = 188/838; 22%), the United States (n = 120/838; 14%), and Finland (n = 85/838; 10%) enrolled the most patients. Changes from baseline in monthly average migraine days over 12 weeks were significantly greater with fremanezumab versus placebo for patients in these countries: Czech Republic (least-squares mean difference versus placebo [95% confidence interval]: quarterly fremanezumab, − 1.9 [− 3.25, − 0.47]; P = 0.009; monthly fremanezumab, − 3.0 [− 4.39, − 1.59]; P < 0.001), the United States (quarterly fremanezumab, − 3.7 [− 5.77, − 1.58]; P < 0.001; monthly fremanezumab, − 4.2 [− 6.23, − 2.13]; P < 0.001), and Finland (quarterly fremanezumab, − 3.0 [− 5.32, − 0.63]; P = 0.014; monthly fremanezumab, − 3.9 [− 6.27, − 1.44]; P = 0.002). Results were comparable for the remaining 9 countries, with the least-squares mean difference versus placebo ranging from – 5.6 to – 2.4 with quarterly fremanezumab and from − 5.3 to − 1.5 with monthly fremanezumab. Incidences of serious adverse events and adverse events leading to discontinuation were low and comparable across countries and treatment groups.

Conclusions

Monthly and quarterly fremanezumab significantly reduced the monthly average number of migraine days versus placebo regardless of country and continent (North America versus Europe) in migraine patients with documented inadequate response to 2 to 4 migraine preventive medication classes.

Trial registration

ClinicalTrials.gov Identifier: NCT03308968.
Genome sequencing and comparative genomic analysis of highly and weakly aggressive strains of Sclerotium rolfsii, the causal agent of peanut stem rot
Authors: Yan Liying , Wang Zhihui , Song Wanduo , Fan Pengmin , Kang Yanping , Lei Yong , Wan Liyun , Huai Dongxin , Chen Yuning , Wang Xin , Sudini Hari , Liao Boshou
Published: April 2021

Background

Stem rot caused by Sclerotium rolfsii is a very important soil-borne disease of peanut. S. rolfsii is a necrotrophic plant pathogenic fungus with an extensive host range and worldwide distribution. It can infect peanut stems, roots, pegs and pods, leading to varied yield losses. S. rolfsii strains GP3 and ZY collected from peanut in different provinces of China exhibited a significant difference in aggressiveness on peanut plants by artificial inoculation test. In this study, de-novo genome sequencing of these two distinct strains was performed aiming to reveal the genomic basis of difference in aggressiveness.

Results

Scleotium rolfsii strains GP3 and ZY, with weak and high aggressiveness on peanut plants, exhibited similar growth rate and oxalic acid production in laboratory. The genomes of S. rolfsii strains GP3 and ZY were sequenced by Pacbio long read technology and exhibited 70.51 Mb and 70.61 Mb, with contigs of 27 and 23, and encoded 17,097 and 16,743 gene models, respectively. Comparative genomic analysis revealed that the pathogenicity-related gene repertoires, which might be associated with aggressiveness, differed between GP3 and ZY. There were 58 and 45 unique pathogen-host interaction (PHI) genes in GP3 and ZY, respectively. The ZY strain had more carbohydrate-active enzymes (CAZymes) in its secretome than GP3, especially in the glycoside hydrolase family (GH), the carbohydrate esterase family (CBM), and the polysaccharide lyase family (PL). GP3 and ZY also had different effector candidates and putative secondary metabolite synthetic gene clusters. These results indicated that differences in PHI, secreted CAZymes, effectors and secondary metabolites may play important roles in aggressive difference between these two strains.

Conclusions

The data provided a further understanding of the S. rolfsii genome. Genomic comparison provided clues to the difference in aggressiveness of S. rolfsii strains.
Long non-coding RNA pairs to assist in diagnosing sepsis
Authors: Zheng Xubin , Leung Kwong-Sak , Wong Man-Hon , Cheng Lixin
Published: April 2021

Background

Sepsis is the major cause of death in Intensive Care Unit (ICU) globally. Molecular detection enables rapid diagnosis that allows early intervention to minimize the death rate. Recent studies showed that long non-coding RNAs (lncRNAs) regulate proinflammatory genes and are related to the dysfunction of organs in sepsis. Identifying lncRNA signature with absolute abundance is challenging because of the technical variation and the systematic experimental bias.

Results

Cohorts (n = 768) containing whole blood lncRNA profiling of sepsis patients in the Gene Expression Omnibus (GEO) database were included. We proposed a novel diagnostic strategy that made use of the relative expressions of lncRNA pairs, which are reversed between sepsis patients and normal controls (eg. lncRNAi > lncRNAj in sepsis patients and lncRNAi < lncRNAj in normal controls), to identify 14 lncRNA pairs as a sepsis diagnostic signature. The signature was then applied to independent cohorts (n = 644) to evaluate its predictive performance across different ages and normalization methods. Comparing to common machine learning models and existing signatures, SepSigLnc consistently attains better performance on the validation cohorts from the same age group (AUC = 0.990 & 0.995 in two cohorts) and across different groups (AUC = 0.878 on average), as well as cohorts processed by an alternative normalization method (AUC = 0.953 on average). Functional analysis demonstrates that the lncRNA pairs in SepsigLnc are functionally similar and tend to implicate in the same biological processes including cell fate commitment and cellular response to steroid hormone stimulus.

Conclusion

Our study identified 14 lncRNA pairs as signature that can facilitate the diagnosis of septic patients at an intervenable point when clinical manifestations are not dramatic. Also, the computational procedure can be generalized to a standard procedure for discovering diagnostic molecule signatures.
Appetite, oral health and weight loss in community-dwelling older men: an observational study from the Concord Health and Ageing in Men Project (CHAMP)
Authors: Takehara Sachiko , Hirani Vasant , Wright F. A. Clive , Naganathan Vasi , Blyth Fiona M. , Le Couteur David G. , Waite Louise M. , Seibel Markus J. , Handelsman David J. , Cumming Robert G.
Published: April 2021

Background

Unintended weight loss and the reduction in appetite are common phenomenon among older people. Reduced appetite has been linked to medication related reductions in saliva production, reduced taste ability and poor oral health. Poor appetite can result in reduced nutrient intake ensuing weight loss. It is possible that poor appetite is a mediating step on the causal pathway between oral health and weight loss. This study investigates whether poor oral health and loss of appetite are related to weight loss.

Methods

This is an observational study where data were obtained from the Concord Health and Ageing in Men Project (CHAMP). Information on socio-demographics, appetite and health related behavior was collected by self-completed questionnaire. Intraoral assessment was conducted by calibrated oral health therapists. Height and weight were measured by trained staff. Regression analysis investigated associations between oral health and appetite as risk factors for weight loss.

Results

Participants included 542 community dwelling older males. 99 older men (18.3%) experienced 5% or more weight loss over 3 years. Men who lost weight from baseline had lower BMI and lower body weight, had higher prevalence of frailty and depression, reported poorer appetite, and had fewer teeth (13.8 ± 9.5) than those who did not lose weight (16.3 ± 9.3). Before adjustment, the prevalence ratio (PR) for weight loss was 1.76 (95% Confidence Interval (CI), 1.19–2.59) for participants with 0–19 natural teeth present compared to those with 20 or more teeth. When adding appetite and other variables to the model, the PR for number of teeth and weight loss was unchanged: 1.78 (95% CI, 1.06–3.00). The mediation analysis showed that the indirect effect of appetite on the association between number of natural teeth on weight loss was not found to be significant.

Conclusion

This study found that number of natural teeth present and appetite are independently related to weight change among elderly men in Australia. Tooth loss can increase the risk of swallowing difficulty leading to change in food preference, avoidance of foods and a decrease in energy intake. Our study showed the importance of oral health interventions to encourage maintenance of 20 or more natural teeth in older people.
RETRACTED ARTICLE: Methylene blue photochemical treatment as a reliable SARS-CoV-2 plasma virus inactivation method for blood safety and convalescent plasma therapy for COVID-19
Authors: Jin Changzhong , Yu Bin , Zhang Jie , Wu Hao , Zhou Xipeng , Yao Hangping , Liu Fumin , Lu Xiangyun , Cheng Linfang , Jiang Miao , Wu Nanping
Published: April 2021

Background

In 2020, a new coronavirus, SARS-CoV-2, quickly spread worldwide within a few months. Although coronaviruses typically infect the upper or lower respiratory tract, the virus RNA can be detected in plasma. The risk of transmitting coronavirus via transfusion of blood products remains. As more asymptomatic infections are identified in COVID-19 cases, blood safety has become particularly important. Methylene blue (MB) photochemical technology has been proven to inactivate lipid-enveloped viruses with high efficiency and safety. The present study aimed to investigate the SARS-CoV-2 inactivation effects of MB in plasma.

Methods

The SARS-CoV-2 virus strain was isolated from Zhejiang University. The live virus was harvested from cultured VERO-E6 cells, and mixed with MB in plasma. The MB final concentrations were 0, 1, 2, and 4 μM. The “BX-1 AIDS treatment instrument” was used at room temperature, the illumination adjusted to 55,000 ± 0.5 million Lux, and the plasma was irradiated for 0, 2, 5, 10, 20, and 40 mins using light at a single wavelength of 630 nm. Virus load changes were measured using quantitative reverse transcription- PCR.

Results

BX-1 could effectively eliminate SARS-CoV-2 within 2 mins in plasma, and the virus titer declined to 4.5 log10 TCID50 (median tissue culture infectious dose)/mL.

Conclusion

BX-1 is based on MB photochemical technology, which was designed to inactivate HIV-1 virus in plasma. It was proven to be safe and reliable in clinical trials of HIV treatment. In this study, we showed that BX-1 could also be applied to inactivate SARS-CoV-2. During the current outbreak, this technique it has great potential for ensuring the safety of blood transfusions, for plasma transfusion therapy in recovering patients, and for preparing inactivated vaccines.
Development of a patient-reported outcome measure for patients who have recovered from a subarachnoid hemorrhage: the “questionnaire for the screening of symptoms in aneurysmal subarachnoid hemorrhage” (SOS-SAH)
Authors: Nobels-Janssen Edith , Abma Inger L. , Verhagen Wim I. M. , Bartels Ronald H. M. A. , van der Wees Philip J. , Boogaarts Jeroen D.
Published: April 2021

Background

Patients who have been successfully treated for an aneurysmal subarachnoid hemorrhage (aSAH) often retain multiple health complaints, including mood disorders, cognitive complaints, fatigue, and problems with social participation. These problems are not always fully addressed during hospital visits or in current outcome measures, such as the modified Rankin score and the Glasgow Outcome Scale. Here, we present the development of the “Questionnaire for the Screening of Symptoms in aneurysmal Subarachnoid Hemorrhage” (SOS-SAH), which screens for the self-reported symptoms of patients with mild disabilities.

Methods

During the development of the SOS-SAH we adhered to the PROM-cycle framework for the selection and implementation of patient-reported outcome measures (PROMs). The SOS-SAH was developed in an iterative process informed by a literature study. Patients and healthcare professionals were involved in the development process through participating in a working group, interviews, and a cognitive validation study.

Results and conclusions

Relevant patient-reported outcomes (PROs) were identified for patients with aSAH. The SOS-SAH was developed primarily using domains and items from existing PROMs and, if necessary, by developing new items. The SOS-SAH consists of 40 items and covers 14 domains: cognitive abilities, hypersensitivity to stimuli, anxiety, depression, fatigue, social roles, personality change, language, vision, taste, smell, hearing, headache, and sexual function. It also includes a proxy measurement for use by family members to assess cognitive functioning and personality change.
The effect of sevoflurane anesthesia for dental procedure on neurocognition in children: a prospective, equivalence, controlled trial
Authors: Zhou Pinping , Zhang Chao , Huang Guijin , Hu Yuan , Ma Wenzhu , Yu Cong
Published: April 2021

Background

Dental procedures under general anesthesia (DGA) was found to improve the oral health-related quality of children’s life. However, some parents and pediatricians expressed concern about the neurotoxicity of general anesthesia. The purpose of this trial was to whether DGA in children has an adverse effect on neurocognition.

Methods

In this prospective, assessor-masked, controlled, equivalence trial, we recruited 340 children younger than 7 years who were undergoing caries treatment between Feb 1, 2019, and Aug 31, 2019, without factors affecting neurodevelopment. They received either sevoflurane-based general anesthesia or awake-local anesthesia. The Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition was used to evaluate the neurocognitive function of children at 6 months after surgery, and the Full-Scale IQ (FSIQ) was selected as the primary outcome. The predefined clinical equivalence margin was 5 (1/3 SD of FSIQ score). If the 95% CI of the difference between the average FSIQ score of the two groups is within − 5 to + 5, then the two groups are equivalent.

Results

The outcome data were obtained from 129 children in the general anesthesia group and 144 in the local anesthesia group. The median length of general anesthesia was 130 min (IQR 110–160). The mean FSIQ score in the general anesthesia group was 103·12 (SD 8.94), and the mean of the local anesthesia group was 103·58 (SD 8.40). There was equivalence in means of FSIQ score between the two groups (local minus general anesthesia 0.46, 95% CI − 2.35 to 1.61). There was no significant difference in FSIQ scores between different age groups and different anesthesia durations. Only the mother’s education could affect the primary outcome.

Conclusions

In this trial, prolonged DGA with a sevoflurane-only anesthetic in preschool children, does not adversely affect neurocognitive function at 6 months after surgery compared with awake-local anesthesia.

Trial registration

Chinese Clinical Trial Registry, ChiCTR1800015216. Registered Mar 15 2018.
Association of source country gender inequality with experiencing assault and poor mental health among young female immigrants to Ontario, Canada
Authors: Lebenbaum Michael , Stukel Therese A. , Saunders Natasha Ruth , Lu Hong , Urquia Marcelo , Kurdyak Paul , Guttmann Astrid
Published: April 2021

Background

Gender inequality varies across countries and is associated with poor outcomes including violence against women and depression. Little is known about the relationship of source county gender inequality and poor health outcomes in female immigrants.

Methods

We used administrative databases to conduct a cohort study of 299,228 female immigrants ages 6–29 years becoming permanent residence in Ontario, Canada between 2003 and 2017 and followed up to March 31, 2020 for severe presentations of suffering assault, and selected mental health disorders (mood or anxiety, self-harm) as measured by hospital visits or death. Poisson regression examined the influence of source-country Gender Inequality Index (GII) quartile (Q) accounting for individual and country level characteristics.

Results

Immigrants from countries with the highest gender inequality (GII Q4) accounted for 40% of the sample, of whom 83% were from South Asia (SA) or Sub-Saharan Africa (SSA). The overall rate of assault was 10.9/10,000 person years (PY) while the rate of the poor mental health outcome was 77.5/10,000 PY. Both GII Q2 (Incident Rate Ratio (IRR): 1.48, 95% Confidence Interval (CI): 1.08, 2.01) and GII Q4 (IRR: 1.58, 95%CI: 1.08, 2.31) were significantly associated with experiencing assault but not with poor mental health. For females from countries with the highest gender inequality, there were significant regional differences in rates of assault, with SSA migrants experiencing high rates compared with those from SA. Relative to economic immigrants, refugees were at increased risk of sustaining assaults (IRR: 2.96, 95%CI: 2.32, 3.76) and poor mental health (IRR: 1.73, 95%CI: 1.50, 2.01). Higher educational attainment (bachelor’s degree or higher) at immigration was protective (assaults IRR: 0.64, 95%CI: 0.51, 0.80; poor mental health IRR: 0.69, 95% CI: 0.60, 0.80).

Conclusion

Source country gender inequality is not consistently associated with post-migration violence against women or severe depression, anxiety and self-harm in Ontario, Canada. Community-based research and intervention to address the documented socio-demographic disparities in outcomes of female immigrants is needed.
Effectiveness of a 23-valent pneumococcal polysaccharide vaccine for the prevention of pneumococcal pneumonia in the elderly with chronic respiratory diseases: a case–control study of a single center
Authors: Masuda Toshihiro , Nakatani Eiji , Shirai Toshihiro , Akamatsu Taisuke , Tamura Kanami , Takahashi Shingo , Tanaka Yuko , Watanabe Hirofumi , Endo Yoshinari , Suzuki Takahito , Saigusa Mika , Yamamoto Akito , Morita Satoru , Sato Yoko , Asada Kazuhiro
Published: April 2021

Background

The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in preventing pneumococcal pneumonia has been controversial.

Methods

To evaluate the effectiveness of the PPSV23 in elderly outpatients with chronic respiratory diseases, we carried out a case–control study, including 4128 outpatients aged ≥ 65 years, in the respiratory department.

Results

There were 320 vaccinated patients, of which 164 were diagnosed with pneumococcal pneumonia. The adjusted odds ratio was 0.39 (95% confidence interval (CI), 0.17 to 0.89). In the subsets consisting of age groups ≥ 70 and ≥ 75 years, the adjusted odds ratio (95% CI) was respectively 0.16 (0.04 to 0.67) and 0.15 (0.02 to 1.12).

Conclusion

This real-world study suggests that PPSV23 can be useful in preventing pneumococcal pneumonia in the elderly with chronic respiratory diseases.