bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of a competence‐based planting support training programme for development agents in Ethiopia
Authors: Tarekegne Chalachew , Wesselink Renate , Biemans Harm J. A. , Mulder Martin
Published: April 2022

Competence‐based education and training (CBE/T) has been implemented in Ethiopia to develop the competences of (future) professionals and to improve their performance. However, empirical evidence that demonstrates the effectiveness of CBE/T is scarce. Positioning the study within the theory of strategic alignment and comprehensive competence‐based training, we used the authentic core job task ‘On‐Site Helping of Farmers during the Planting of Maize’, of Development Agents as problem context and conducted an experimental‐longitudinal research study including multirater performance assessment. The study compared competence development of the Development Agents who received training that could be characterized as ‘High‐CBT’ (N = 33) and ‘Low‐CBT’ (N = 32). ‘High‐CBT’ means that in these training programmes, principles of competence‐based training were used more completely than in the ‘Low‐CBT’ programmes. Experts rated the competence levels of the Development Agents and Development Agents rated their own competence levels. Both groups did that before and after the training. Individual Development Agent performance was also rated by Trained Assessors. Longitudinally, Development Agent performance data was collected during one production year at three points in time. Development Agent's competence development in the ‘High‐CBT’ training condition was higher than in the ‘Low‐CBT’ condition. Observations made on each Development Agent's performance by Trained Assessors both in the Farmer Training Centres and in the authentic job situations, generally confirmed better performance of the ‘High‐CBT’ group compared with the ‘Low‐CBT’ group. The finding contributes to the state of research on the relationship between competence development and performance improvement, which is theoretically postulated although less empirically tested.
The influence of ‘soft’ fair work regulation on union recovery: A case of re‐recognition in the Scottish voluntary social care sector
Authors: Cunningham Ian , James Philip , Baluch Alina
Published: April 2022

This longitudinal case study contributes to debates concerning how ‘soft’ and ‘hard’ forms of regulation can interact to contribute to the advancement of worker rights. More specifically, the article explores the contribution of Scotland's soft fair work (FW) programme and the UK's hard statutory recognition procedure to union re‐recognition in a voluntary sector social care provider. In combination, hard and soft regulations are found to have added breadth to the pressures for re‐recognition exerted by the union, bringing reputational and financial costs associated with derecognition to the employer. Concerns nevertheless arose regarding the depth of impact from this interaction due to union compromises on key issues in the final recognition agreement. Due to the specific public service context of the study, doubts are also expressed regarding the potential for unions in other hard to organise sectors to achieve similar outcomes.
Tildrakizumab efficacy and safety in patients with psoriasis and concomitant metabolic syndrome: post hoc analysis of 5‐year data from reSURFACE 1 and reSURFACE 2
Authors: Fernandez A.P. , Dauden E. , Gerdes S. , Lebwohl M.G. , Menter M.A. , Leonardi C.L. , Gooderham M. , Gebauer K. , Tada Y. , Lacour J.P. , Bianchi L. , Egeberg A. , Pau‐Charles I. , Mendelsohn A.M. , Rozzo S.J. , Mehta N.N.
Published: April 2022

Background

Limited data are available on long‐term efficacy and safety of biologics in patients with psoriasis and metabolic syndrome (MetS), a common comorbidity.

Objectives

This analysis updates tildrakizumab efficacy and safety for up to 5 years in patients with and without MetS.

Methods

This was a post hoc analysis of the double‐blind, randomized, placebo‐controlled, phase 3 reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754) trials in adult patients with moderate to severe chronic plaque psoriasis. Analyses included data through Week 244 from patients who continuously received tildrakizumab 100 (TIL100) or 200 mg (TIL200) and entered the extension studies, stratified by baseline MetS status. Efficacy was assessed via Psoriasis Area and Severity Index (PASI) scores. Safety was evaluated from exposure‐adjusted incidence rates (EAIRs) of treatment‐emergent adverse events (TEAEs).

Results

reSURFACE 1 and reSURFACE 2 analyses included 26 and 44 TIL100‐treated patients with MetS, 98 and 167 TIL100‐treated patients without MetS, 34 and 30 TIL200‐treated patients with MetS, and 111 and 130 TIL200‐treated patients without MetS, respectively. There were no clinically relevant differences in PASI 75/90/100 response rates at Week 244 between patients with vs without MetS. The proportion of patients with vs without MetS achieving absolute PASI score <3 at Week 244 was 53.8% vs 69.4% and 77.3% vs 80.8% in reSURFACE 1 and 2, respectively, for TIL100‐treated patients and 58.8% vs 72.1% and 63.3% vs 72.3%, respectively, for TIL200‐treated patients. In both studies, median reduction from baseline PASI score at all time points in patients with vs without MetS was >83% vs >89% for TIL100 and >85% vs >90% for TIL200. Pooled EAIRs of TEAEs, serious TEAEs, and TEAEs of special interest were similar in patients with and without MetS.

Conclusions

Tildrakizumab maintains efficacy and a favorable safety profile over 5 years in patients with psoriasis regardless of MetS status.
Molecular evolutionary analysis of the SM and SNARE vesicle fusion machinery in ciliates shows concurrent expansions in late secretory machinery
Authors: Kaur Harpreet , Richardson Elisabeth , Kamra Komal , Dacks Joel B.
Published: April 2022

Protists in the phylum Ciliophora possess a complex membrane‐trafficking system, including osmoregulatory Contractile Vacuoles and specialized secretory organelles. Molecular cell biological investigations in Tetrahymena thermophila have identified components of the protein machinery associated with the secretory organelles, mucocysts. The Qa‐SNARE Syn7lp plays a role in mucocyst biogenesis as do subunits of the CORVET tethering complex (specifically Vps8). Indeed, Tetrahymena thermophila possesses expanded gene complements of several CORVET components, including Vps33 which is also a Sec1/Munc18 (SM) protein that binds Qa‐SNAREs. Moreover, the Qa‐SNAREs in Paramecium tetraurelia have been localized to various endomembrane organelles. Here, we use comparative genomics and phylogenetics to determine the evolutionary history of the SM and Qa‐SNARE proteins across the Ciliophora. We identify that the last ciliate common ancestor possessed the four SM proteins and six Qa‐SNAREs common to eukaryotes, including the uncommonly retained Syntaxin 17. We furthermore identify independent expansion of these protein families in several ciliate classes, including concurrent expansions of the SM protein‐Qa SNARE partners Sec1:SynPM in the oligohymenophorean ciliates lineage, consistent with novel Contractile Vacuole specific innovations. Overall, these data are consistent with SM proteins and Qa‐SNAREs being a common set of components for endomembrane modulation in the ciliates.
A review on the encapsulation of bioactive components using spray‐drying and freeze‐drying techniques
Authors: Kandasamy Sengodan , Naveen Rajshri
Published: April 2022

Bioactive compounds are a type of chemical substance found in plant sources. Lycopene, carotenoids, phytochemicals, phenolic compounds, and anthocyanin are a few bioactive compounds. These compounds are rich in antimicrobial, antioxidant, and free radical‐scavenging properties. But these compounds are easily degraded. In order to enhance the chemical stability and the retention properties of functional ingredients, encapsulation is indispensable. This paper reviews the two important methods of encapsulation of bioactive components and the novelties in these techniques. Spray‐drying and freeze‐drying techniques are commonly used for encapsulation in the food and pharmaceutical industries. The former is a quick and high‐temperature process, while the latter is a time‐consuming and low‐temperature procedure. The inlet temperature during spray drying is maintained between 120 and 190°C, whereas during freeze drying, a temperature of −80°C to −20°C is maintained. For effective encapsulation, the optimization of the process conditions such as the temperature, pressure, feed rate, airflow rates, and selection of wall materials are essential. In this paper, the influence of these parameters on encapsulation efficiency and product stability is also discussed.

Practical Applications

The spray‐drying and freeze‐drying techniques find their application in the food and chemical industries for the purpose of encapsulation and drying. The former technique helps transform liquid foods to powder and thereby extending their shelf life. The encapsulation of some biologically active components helps better retention and delivery of the components. Spray drying is a technique in which liquid foods are converted to powdered form. These techniques have been used for a very long time in the dairy industry. But in recent times, they have been used in the pharmaceutical industries as well. Their main application in the pharmaceutical industry is drug delivery. Freeze drying is a low‐temperature encapsulation process which is mainly used for the encapsulation of functional foods. The most commonly spray‐dried active materials include oleoresins, natural food colors, natural antioxidants, lipids, flavors, and functional foods. Probiotic sources such as bacterial cultures are the main freeze‐dried products. In this review, the practical applications of the techniques are elaborated.
Gamma‐glutamyl transpeptidase dynamics as a biomarker for advanced fibrosis in non‐alcoholic fatty liver disease
Authors: Ha Yeonjung , Chon Young Eun , Kim Mi Na , Lee Joo Ho , Hwang Seong Gyu
Published: April 2022

Background and Aim

It is unclear whether changes in lipid profile and liver biochemistry are associated with advanced fibrosis.

Methods

Patients diagnosed with non‐alcoholic fatty liver disease (NAFLD) between 2009 and 2017 were included. The changes in blood tests were calculated as follows: [(value at 6 months − value at baseline)/value at baseline] × 100. The endpoint was advanced fibrosis determined by the NAFLD fibrosis score, calculated every year from diagnosis until 2019. Cox proportional hazards models were used to identify factors predicting advanced fibrosis.

Results

After a median follow‐up of 31.7 (19.4–50.8) months, advanced fibrosis occurred in 64 (6.3%) of 1021 patients. Gamma‐glutamyl transpeptidase (GGT) levels (72.9 vs 51.1 IU/L; P = 0.23) and ΔGGT (+6.0% vs −6.9%; P = 0.06) were higher in the advanced fibrosis group. ΔGGT (hazard ratio [HR] 1.03; P < 0.001) was significantly associated with advanced fibrosis after adjusting for age and platelet count. The positive ΔGGT group showed a higher incidence of advanced fibrosis and the 1‐standard deviation increment in ΔGGT showed a significant association with advanced fibrosis both in statin users (HR, 1.35) and in non‐users (HR, 1.31; Ps < 0.05). The restricted cubic spline model identified a positive correlation between ΔGGT and the NAFLD fibrosis scores (P < 0.001). ΔGGT showed sensitivity of 64.2%, specificity of 52.6%, and negative predictive value of 98.3% in predicting advanced fibrosis.

Conclusions

ΔGGT calculated at 6 months following NAFLD diagnosis is associated with advanced fibrosis.
Adverse events following third dose of mRNA COVID‐19 vaccination among nursing home residents who received the primary series
Authors: Bardenheier Barbara H. , White Elizabeth M. , Blackman Carolyn , Gravenstein Stefan , Gutman Roee , Sarkar Indra Neil , Feifer Richard A. , McConeghy Kevin , Nanda Aman , Duprey Matthew , Mor Vincent
Published: April 2022

Background

We sought to compare rates of adverse events among nursing home residents who received an mRNA COVID‐19 vaccine booster dose with those who had not yet received their booster.

Methods

We assessed a prospective cohort of 11,200 nursing home residents who received a primary COVID‐19 mRNA vaccine series at least 6 months prior to September 22, 2021 and received a third “booster dose” between September 22, 2021 and February 2, 2022. Residents lived in 239 nursing homes operated by Genesis HealthCare, spanning 21 U.S. states. We screened electronic health records for 20 serious vaccine‐related adverse events that are monitored following receipt of COVID‐19 vaccination by the CDC's Vaccine Safety Datalink. We matched boosted and yet‐to‐be boosted residents during the same time period, comparing rates of events occurring 14 days after booster administration with those occurring 14 days prior to booster administration. To supplement previously reported background rates of adverse events, we report background rates of medical conditions among nursing home residents during 2020, before COVID‐19 vaccines were administered in nursing homes. Events occurring in 2021–2022 were confirmed by physician chart review. We report unadjusted rates of adverse events and used a false discovery rate procedure to adjust for multiplicity of events tested.

Results

No adverse events were reported during the 14 days post‐booster. A few adverse events occurred prior to booster (ischemic stroke: 49.4 per 100,000 residents, 95% CI: 21.2, 115.7; venous thromboembolism: 9.9 per 100,000 residents, 95% CI: 1.7, 56.0), though differences in event rates pre‐ versus post‐booster were not statistically significant (p < 0.05) after adjusting for multiple comparisons. No significant differences were detected between post‐booster vaccination rates and prior year 14‐day background rates of medical conditions.

Conclusions

No safety signals were detected following a COVID‐19 mRNA vaccine booster dose in this large multi‐state sample of nursing home residents.
Age‐related differences in symptoms in older emergency department patients with COVID‐19: Prevalence and outcomes in a multicenter cohort
Authors: Goldberg Elizabeth M. , Southerland Lauren T. , Meltzer Andrew C. , Pagenhardt Justine , Hoopes Ryan , Camargo Carlos A. , Kline Jeffrey A.
Published: April 2022

Background

Older adults represent a disproportionate share of severe COVID‐19 presentations and fatalities, but we have limited understanding of the differences in presentation by age and the association between less typical emergency department (ED) presentations and clinical outcomes.

Methods

This retrospective cohort study used the RECOVER Network registry, a research collaboration of 86 EDs in 27 U.S. states. We focused on encounters with a positive nasopharyngeal swab for SARS‐CoV‐2, and described their demographics, clinical presentation, and outcomes. Sequential multivariable logistic regressions examined the strength of association between age cohort and outcomes.

Results

Of 4536 encounters, median patient age was 55 years, 49% were women, and 34% were non‐Hispanic Black persons. Cough was the most common presenting complaint across age groups (18–64, 65–74, and 75+): 71%, 67%, and 59%, respectively (p < 0.001). Neurological symptoms, particularly altered mental status, were more common in older adults (2%, 11%, 26%; p < 0.001). Patients 75+ had the greatest odds of ED index visit admission of all age groups (adjusted odds ratio [aOR] 6.66; 95% CI 5.23–8.56), 30‐day hospitalization (aOR 7.44; 95% CI 5.63–9.99), and severe COVID‐19 (aOR 4.26; 95% CI 3.45–5.27). Compared to individuals with alternate presentations and adjusting for age, patients with typical symptoms (fever, cough and/or shortness of breath) had similar odds of ED index visit admission (aOR 1.01; 95% CI 0.81–1.24), potentially higher odds of 30‐day hospitalization (aOR 1.23; 95% CI 1.00–1.53), and greater odds of severe COVID‐19 (aOR 1.46; 95% CI 1.12–1.90).

Conclusions

Older patients with COVID‐19 are more likely to have presentations without the most common symptoms. However, alternate presentations of COVID‐19 in older ED patients are not associated with greater odds of mechanical ventilation and/or death. Our data highlights the importance of a liberal COVID‐19 testing strategy among older ED patients to facilitate accurate diagnoses and timely treatment and prophylaxis.
Estrogenic regulation of reproduction and energy homeostasis by a triumvirate of hypothalamic arcuate neurons
Authors: Stincic Todd L. , Kelly Martin J.
Published: April 2022

Pregnancy is energetically demanding and therefore, by necessity, reproduction and energy balance are inextricably linked. With insufficient or excessive energy stores a female is liable to suffer complications during pregnancy or produce unhealthy offspring. Gonadotropin‐releasing hormone neurons are responsible for initiating both the pulsatile and subsequent surge release of luteinizing hormone to control ovulation. Meticulous work has identified two hypothalamic populations of kisspeptin (Kiss1) neurons that are critical for this pattern of release. The involvement of the hypothalamus is unsurprising because its quintessential function is to couple the endocrine and nervous systems, coordinating energy balance and reproduction. Estrogens, more specifically 17β‐estradiol (E2), orchestrate the activity of a triumvirate of hypothalamic neurons within the arcuate nucleus (ARH) that govern the physiological underpinnings of these behavioral dynamics. Arising from a common progenitor pool, these cells differentiate into ARH kisspeptin, pro‐opiomelanocortin (POMC), and agouti related peptide/neuropeptide Y (AgRP) neurons. Although the excitability of all these subpopulations is subject to genomic and rapid estrogenic regulation, Kiss1 neurons are the most sensitive, reflecting their integral function in female fertility. Based on the premise that E2 coordinates autonomic functions around reproduction, we review recent findings on how Kiss1 neurons interact with gonadotropin‐releasing hormone, AgRP and POMC neurons, as well as how the rapid membrane‐initiated and intracellular signaling cascades activated by E2 in these neurons are critical for control of homeostatic functions supporting reproduction. In particular, we highlight how Kiss1 and POMC neurons conspire to inhibit AgRP neurons and diminish food motivation in service of reproductive success.
The lived experience of adults and parents: Transitioning from paediatric to adult health care with oesophageal atresia and tracheo‐oesophageal fistula
Authors: Haig‐Ferguson Andrew , Wallace Vuokko , Davis Cara
Published: April 2022

Aim and Objective

To explore the experience of healthcare transition from paediatric to adult health care for adults born with oesophageal atresia and tracheo‐oesophageal fistula (OA/TOF) and parents.

Background

OA/TOF is a rare and chronic health condition that can require lifelong medical follow‐up and management. There is evidence to suggest that transitioning from paediatric to adult health care can be problematic for people with rare and chronic conditions, including OA/TOF. The previous literature suggests that the experience of transitioning with a rare condition is more complex than transitioning with a common chronic condition.

Design

The current study was a qualitative, cross‐sectional, survey‐based study.

Methods

Data were collected through an online survey. Parents of children born with OA/TOF (n = 23) and adults born with OA/TOF (n = 16) were recruited through a UK‐based OA/TOF patient charity. Data from six open‐ended questions were analysed using a hybrid approach combining elements of inductive and deductive thematic analyses. Throughout the research process, the SRQR were followed.

Results

Five themes were constructed during the analysis, reflecting the experience of parents and adults transitioning from paediatric to adult health care: thrown into the unknown; a cultural shift; stepping back and stepping up; ‘no transition as such’; and living with uncertainty.

Conclusions

The findings suggested that a formalised, managed healthcare transition is not commonly experienced by people born with OA/TOF and parents.

Relevance to Clinical Practice

We recommend a formalised healthcare transition process in OA/TOF, including preparation for transition and having a named key worker to manage the multidisciplinary transition process. The results also highlighted the need for adults born with OA/TOF to have access to a specialist health service with knowledge and understanding of issues related to OA/TOF.
Comparison of the modified laparoscopic Vecchietti and Davydov colpoplasty techniques in Mayer‐Rokitansky‐Küster‐Hauser syndrome: A long‐term follow‐up analysis
Authors: Yang Xinyun , Zhu Linling , Wang Yan Jing , Tong Baoqin , Zhong Shuangshuang , Yang Chunbo , Liang Junxiao , Jin Hangmei , Xie Zhenwei
Published: April 2022

Aims

To introduce and compare the modified laparoscopic Vecchietti and Davydov techniques for vaginoplasty in patients with Mayer‐Rokitansky‐Küster‐Hauser (MRKH) syndrome. Moreover, the long‐term treatment of vaginal agenesis was followed‐up.

Methods

This comparative retrospective cohort study enrolled a total of 53 women with MRKH syndrome. The patients underwent surgical creation of a neovagina including 32 patients who underwent the modified laparoscopic Vecchietti technique, and 21 patients who underwent the modified laparoscopic Davydov technique from January 2009 to February 2019. The perioperative parameters, complications, anatomical, and functional outcomes of the two groups were compared. Patients' sexual functions were evaluated over a long‐term follow‐up using the female sexual function index (FSFI) and the revised female sexual distress scale (FSDS‐R).

Results

The medians (25th–75th) of the surgery duration for modified Vecchietti procedures was 50.0 (40.0–59.0) minutes, comparing to 135.0 (117.5–162.5) min for Davydov procedures (p < 0.001). The intraoperative blood loss was 20 (7.5–20.0) mL versus 50.0 (50.0–100.0) mL using the modified Vecchietti and Davydov approaches (p < 0.001), respectively. In the 39 follow‐up cases, the lengths of the neovagina of the patients for Vecchietti group versus Davydov group were 7.9 ± 1.0 cm versus 8.6 ± 1.2 cm at 6 months after the vaginoplasty and 8.3 ± 0.7 cm versus 8.5 ± 0.9 cm after 2 years. There was no statistical difference in the FSFI and FSDS‐R scores between the two groups.

Conclusions

Both the modified Davydov and Vecchietti laparoscopic procedures successfully achieved optimal anatomic and functional outcomes in treatments of vaginal agenesis. The modified Vecchietti technique is relatively simpler than the modified Davydov technique.
Iron deficiency screening is a key issue in chronic inflammatory diseases: A call to action
Authors: Cacoub Patrice , Choukroun Gabriel , Cohen‐Solal Alain , Luporsi Elisabeth , Peyrin‐Biroulet Laurent , Peoc'h Katell , Andrieu Valérie , Lasocki Sigismond , Puy Hervé , Trochu Jean‐Noël
Published: April 2022

Iron deficiency is frequent in patients with chronic inflammatory conditions (e.g., chronic heart failure, chronic kidney disease, cancers, and bowel inflammatory diseases). Indeed, high concentrations of inflammatory cytokines increase hepcidin concentrations that lead to the sequestration of iron in cells of the reticuloendothelial system (functional iron deficiency). Iron parameters are often assessed only in the context of anemia, but iron deficiency, even without anemia, is present in about half of patients with inflammatory conditions. Iron deficiency worsens underlying chronic diseases and is an independent factor of morbidity and mortality. In daily practice, the most effective biomarkers of iron status are serum ferritin, which reflects iron storage, and transferrin saturation, which reflects the transport of iron. Serum ferritin is increased in an inflammatory context, and there is still no consensus on the threshold to be used in chronic inflammatory conditions. Nevertheless, recent recommendations of international guidelines agreed to define iron deficiency by serum ferritin <100 µg/L and/or transferrin saturation <20%. Iron parameters remain, however, insufficiently assessed in patients with chronic inflammatory conditions. Indeed, clinical symptoms of iron deficiency, such as fatigue, are not specific and often confused with those of the primary disease. Iron repletion, preferably by the intravenous route to bypass tissue sequestration, improves clinical signs and quality of life. Because of the negative impact of iron deficiency on chronic inflammatory diseases and the efficacy of intravenous iron repletion, screening of iron parameters should be part of the routine examination of all patients with chronic inflammatory diseases.
Immunoexpression of oral brush biopsy enhances the accuracy of diagnosis for oral lichen planus and lichenoid lesions
Authors: Idrees Majdy , Shearston Kate , Farah Camile S. , Kujan Omar
Published: April 2022

Background

This study assessed the efficacy of using oral liquid‐based brush cytology (OLBC) coupled with immunostained cytology‐derived cell‐blocks, quantified using machine‐learning, in the diagnosis of oral lichen planus (OLP).

Methods

Eighty‐two patients diagnosed clinically with either OLP or oral lichenoid lesion (OLL) were included. OLBC samples were obtained from all patients before undergoing surgical biopsy. Liquid‐based cytology slides and cell‐blocks were prepared and assessed by cytomorphology and immunocytochemistry for four antibodies (Ki‐67, BAX, NF‐κB‐p65, and AMACR). For comparison purposes, a sub‐group of 31 matched surgical biopsy samples were selected randomly and assessed by immunohistochemistry. Patients were categorized according to their definitive diagnoses into OLP, OLL, and clinically lichenoid, but histopathologically dysplastic lesions (OEDL). Machine‐learning was utilized to provide automated quantification of positively stained protein expression.

Results

Cytomorphological assessment was associated with an accuracy of 77.27% in the distinction between OLP/OLL and OEDL. A strong concordance of 92.5% (κ = 0.84) of immunostaining patterns was evident between cell‐blocks and tissue sections using machine‐learning. A diagnostic index using a Ki‐67‐based model was 100% accurate in detecting lichenoid cases with epithelial dysplasia. A BAX‐based model demonstrated an accuracy of 92.16%. The accuracy of cytomorphological assessment was greatly improved when it was combined with BAX immunoreactivity (95%).

Conclusions

Cell‐blocks prepared from OLBC are reliable and minimally‐invasive alternatives to surgical biopsies to diagnose OLLs with epithelial dysplasia when combined with Ki‐67 immunostaining. Machine‐learning has a promising role in the automated quantification of immunostained protein expression.
Entrepreneurship and new product development: Exploring the “advantage of youth” and “business acumen” views
Authors: Grilli Luca
Published: April 2022

We explore the relevance of two different views on new product development (NPD) drivers, defined as “advantage of youth” and “business acumen.” The two arguments, that establish a negative relationship between an individual's age and NPD and a positive impact of professional experience on NPD, are theoretically contextualized and empirically tested in the entrepreneurship domain. Considering a sample of more than 4000 Italian entrepreneurs of innovative start‐ups, a series of econometric analyses confirm that both effects apply and reveal interesting nuances as to the relevance of the age effect and the relative importance of different dimensions of entrepreneurs' business acumen on NPD. Further additional analyses highlight how both the “advantage of youth” and “business acumen” do not necessarily lead to successful entrepreneurial NPD, but at the same time, they both are found to importantly characterize top performers among entrepreneurs engaging in NPD. Overall, this in‐depth analysis on entrepreneurial NPD and its drivers underlies the importance of a micro‐founded and individual‐based approach in the study of new product dynamics, and in doing so, it contributes to enrich the upper echelons perspective and related frameworks on innovation outcomes through entrepreneurship. By theorizing and documenting those personal demographic and human capital traits which are mostly associated with entrepreneurial NPD, a series of interesting implications quite naturally descend for several stakeholders: (prospective) entrepreneurs, managers who aim at nurturing an intrapreneurship culture within their companies and policy makers interested in increasing dynamic efficiency in the economic system through the launch of new products and services.
Insomnia disorder: State of the science and challenges for the future
Authors: Riemann Dieter , Benz Fee , Dressle Raphael J. , Espie Colin A. , Johann Anna F. , Blanken Tessa F. , Leerssen Jeanne , Wassing Rick , Henry Alasdair L. , Kyle Simon D. , Spiegelhalder Kai , Van Someren Eus J. W.
Published: April 2022

Insomnia disorder comprises symptoms during night and day that strongly affect quality of life and wellbeing. Prolonged sleep latency, difficulties to maintain sleep and early morning wakening characterize sleep complaints, whereas fatigue, reduced attention, impaired cognitive functioning, irritability, anxiety and low mood are key daytime impairments. Insomnia disorder is well acknowledged in all relevant diagnostic systems: Diagnostic and Statistical Manual of the American Psychiatric Association, 5th revision, International Classification of Sleep Disorders, 3rd version, and International Classification of Diseases, 11th revision. Insomnia disorder as a chronic condition is frequent (up to 10% of the adult population, with a preponderance of females), and signifies an important and independent risk factor for physical and, especially, mental health. Insomnia disorder diagnosis primarily rests on self‐report. Objective measures like actigraphy or polysomnography are not (yet) part of the routine diagnostic canon, but play an important role in research. Disease concepts of insomnia range from cognitive‐behavioural models to (epi‐) genetics and psychoneurobiological approaches. The latter is derived from knowledge about basic sleep–wake regulation and encompass theories like rapid eye movement sleep instability/restless rapid eye movement sleep. Cognitive‐behavioural models of insomnia led to the conceptualization of cognitive‐behavioural therapy for insomnia, which is now considered as first‐line treatment for insomnia worldwide. Future research strategies will include the combination of experimental paradigms with neuroimaging and may benefit from more attention to dysfunctional overnight alleviation of distress in insomnia. With respect to therapy, cognitive‐behavioural therapy for insomnia merits widespread implementation, and digital cognitive‐behavioural therapy may assist delivery along treatment guidelines. However, given the still considerable proportion of patients responding insufficiently to cognitive‐behavioural therapy for insomnia, fundamental studies are highly necessary to better understand the brain and behavioural mechanisms underlying insomnia. Mediators and moderators of treatment response/non‐response and the associated development of tailored and novel interventions also require investigation. Recent studies suggest that treatment of insomnia may prove to add significantly as a preventive strategy to combat the global burden of mental disorders.
Sleep medicine guidelines, recommendations for clinical practice: the role of the European Sleep Research Society
Authors: Penzel Thomas
Published: April 2022

The European Sleep Research Society (ESRS) has a strong focus on sleep research in Europe. In addition, the ESRS supports sleep medicine in Europe by providing a platform of exchange and communication for the national sleep societies of all European countries and by providing committees that support co‐ordination for important clinical activities. These committees help on clinical guidelines, certification of sleep centres, certification of sleep physicians, psychologists, sleep scientists, sleep technologists, and medical education in sleep medicine. For education in sleep medicine, a “Catalogue on knowledge and skills” has been developed based on a consensus process. This catalogue serves as the backbone for a European textbook on sleep medicine and as the basis for courses, qualifications, and examinations of somnologists in Europe. These activities are devoted to improving and maintain a high quality of care in Europe for sleep medicine services.
Pharmacology, safety, efficacy and clinical uses of the COX‐2 inhibitor robenacoxib
Authors: Lees Peter , Toutain Pierre‐Louis , Elliott Jonathan , Giraudel Jerome M. , Pelligand Ludovic , King Jonathan N.
Published: April 2022

Robenacoxib is a veterinary‐approved non‐steroidal anti‐inflammatory drug (NSAID) of the coxib group. It possesses anti‐hyperalgesic, anti‐inflammatory and anti‐pyretic properties. Robenacoxib inhibits the cyclooxygenase (COX)‐2 isoform of COX selectively (in vitro IC50 ratios COX‐1:COX‐2, 129:1 in dogs, 32:1 in cats). At registered dosages (2 mg/kg subcutaneously in dogs and cats, 1–4 mg/kg orally in dogs and 1–2.4 mg/kg orally in cats), robenacoxib produces significant inhibition of COX‐2 whilst sparing COX‐1. The pharmacokinetic (PK) profile of robenacoxib is characterized by a high degree of binding to plasma proteins (>98%) and moderate volume of distribution (at steady state, 240 ml/kg in dogs and 190 ml/kg in cats). In consequence, the terminal half‐life in blood (<2 h) is short, despite moderate body clearance (0.81 L/kg/h) in dogs and low clearance (0.44 L/kg/h) in cats. Excretion is principally in the bile (65% in dogs and 72% in cats). Robenacoxib concentrates in inflamed tissues, and clinical efficacy is achieved with once‐daily dosing, despite the short blood terminal half‐life. In dogs, no relevant breed differences in robenacoxib PK have been detected. Robenacoxib has a wide safety margin; in healthy laboratory animals daily oral doses 20‐fold (dog, 1 month), eight‐fold (cat, 6 weeks) and five‐fold (dog, 6 months) higher than recommended clinical doses were well tolerated. Clinical efficacy and safety have been demonstrated in orthopaedic and soft tissue surgery, and in musculoskeletal disorders in dogs and cats.
Functional traits and propagule pressure explain changes in the distribution and demography of non‐native trees in Spain
Authors: Lara‐Romero Carlos , Ruiz‐Benito Paloma , Castro‐Díez Pilar
Published: April 2022

Questions

Non‐native tree species (NNT) may bring about economic benefits, but also threats to ecosystems, mostly if they show expansive trends.

Location

A set of 12,000 permanent plots of the second (1986–1996), third (1997–2007) and fourth (2008–2017) Spanish Forest Inventory.

Methods

We quantified changes over time (1986–2017) of the NNT present in forests of peninsular Spain and we assessed how NNT’s traits, propagule pressure and human perception of NNT explain changes in distribution and demography of NNT. We quantified changes in four demographic parameters of every NNT: changes in the occupancy of species (number of plots where the species are present), annual changes in tree density and basal area, and tree growth. To explain the observed species trends, we selected functional traits related to the resource acquisition strategy, and key human drivers.

Results

Most of the NNT expanded their occupancy in the study area and increased their density, basal area, and tree growth through time. Increases in tree density and growth were greater in NNT with greater tolerance for low water potentials, with low specific leaf area, and with high propagule pressure. Increases in basal area were greater with high height of the NNT.

Conclusions

The overall increase in occupancy suggests that there is room for expansion of NNT in Spain. This knowledge will help to predict the dynamics of NNT already present in Spain and identify risks for forest biodiversity.
The DEAD‐box helicase DDX3x ameliorates non‐alcoholic fatty liver disease via mTORC1 signalling pathway
Authors: Liu Peihao , Zhang Yuwei , Tang Chenxi , Cen Li , Chen Yishu , Li Sha , Chen Xueyang , Yu Mengli , Zhang Jie , Zhang Xiaofen , Zeng Hang , Xu Chengfu , Yu Chaohui
Published: April 2022

Background & Aims

The DEAD (Asp‐Glu‐Ala‐Asp)‐box helicase family member DDX3x has been proven to involve in hepatic lipid disruption during HCV infection. However, the role of DDX3x in non‐alcoholic fatty liver disease (NAFLD), in which lipid homeostasis is severely disrupted, remains unclear. Here, we aimed to illustrate the potential role of DDX3x in NAFLD.

Methods

DDX3x protein levels were evaluated in NAFLD patients and NAFLD models via immunohistochemistry or western blotting. In vivo ubiquitin assay was performed to identify the ubiquitination levels of DDX3x in the progression of steatosis. DDX3x protein levels in mice livers were manipulated by adeno‐associated virus‐containing DDX3x short hairpin RNA or DDX3x overexpression plasmid. Hepatic or serum triglyceride and total cholesterol were evaluated and hepatic steatosis was confirmed by haematoxylin and eosin staining and oil red o staining. Western blotting was performed to identify the underlying mechanisms of DDX3x involving in the progression of NAFLD.

Results

DDX3x protein levels were significantly decreased in NAFLD patients and NAFLD models. DDX3x protein might be degraded via ubiquitin–proteasome system in the progression of steatosis. Knockdown of hepatic DDX3x exacerbated HFD‐induced hepatic steatosis in mice, while overexpression of hepatic DDX3x alleviated HFD‐induced hepatic steatosis in mice. Further explorative experiments revealed that knockdown of DDX3x could lead to the overactivation of mTORC1 signalling pathway which exacerbates NAFLD.

Conclusions

DDX3x involved in the progression of NAFLD via affecting the mTORC1 signalling pathway. DDX3x might be a potential target for NAFLD treatment.
Hepatic exosomes with declined MiR‐27b‐3p trigger RIG‐I/TBK1 signal pathway in macrophages
Authors: You Jie , Wu Wenyu , Lu Mengxin , Xie Yanghao , Miao Rui , Gu Misi , Xi Dong , Yan Weiming , Wu Di , Wang Xiaojing , Chen Tao , Ning Qin , Han Meifang
Published: April 2022

Background and Aims

Evidence suggests that interferon alpha (IFNα) plays an essential role in decreasing the HBsAg quantification and elevating the rate of clinical cure in chronic hepatitis B (CHB). However, the mechanisms underlying the effects of the exosomes on the expression of host genes in IFNα treatment remain unclear.

Methods

CHB patients with IFNα treatment were divided into responders and non‐responders according to the degree of HBsAg decline. Through microRNA sequencing and a series of molecular biology methods, the key microRNAs in serum exosomes associated with clinical antiviral response of Peg‐IFNα treatment in nucleotide analogue‐treated CHB patients were investigated. The roles of exosomal miRNAs on the IFNα signal pathway were explored in macrophages.

Results

MicroRNA sequencing and RT‐qPCR assays confirmed six distinctly declined miRNAs in serum exosomes of responders at week 12 compared with levels at baseline. Exosomes with declined miR27b‐3p in the serum of Peg‐IFNα‐treated responders activated phosphorylation of interferon regulatory factor 3/7 (IRF3/7) in IFNα synthesis pathway in macrophages. However, miR27b‐3p overexpression in HepAD38 cells suppressed IFNα synthesis in macrophages, resulting in insufficient ability to eliminate HBV, whereas the inhibitory effect could be blocked by inhibitors of exosomes release. Luciferase assay showed miR‐27b‐3p directly suppressed retinoic acid‐inducible gene I (RIG‐I) and TANK‐binding kinase 1 (TBK1) expressions, and these effects could be abrogated in mutation experiments.

Conclusions

In IFNα treatment, exosomes with declined miR‐27b‐3p triggered activation of RIG‐I/TBK1 signalling in macrophages against HBV. Serum exosomal miR‐27‐3p might represent a potential biomarker for patients with CHB.
Whole‐genome analysis of multiple wood ant population pairs supports similar speciation histories, but different degrees of gene flow, across their European ranges
Authors: Portinha Beatriz , Avril Amaury , Bernasconi Christian , Helanterä Heikki , Monaghan Josie , Seifert Bernhard , Sousa Vitor C. , Kulmuni Jonna , Nouhaud Pierre
Published: April 2022

The application of demographic history modelling and inference to the study of divergence between species has become a cornerstone of speciation genomics. Speciation histories are usually reconstructed by analysing single populations from each species, assuming that the inferred population history represents the actual speciation history. However, this assumption may not be met when species diverge with gene flow, for example, when secondary contact may be confined to specific geographic regions. Here, we tested whether divergence histories inferred from heterospecific populations may vary depending on their geographic locations, using the two wood ant species Formica polyctena and F. aquilonia. We performed whole‐genome resequencing of 20 individuals sampled in multiple locations across the European ranges of both species. Then, we reconstructed the histories of distinct heterospecific population pairs using a coalescent‐based approach. Our analyses always supported a scenario of divergence with gene flow, suggesting that divergence started in the Pleistocene (c. 500 kya) and occurred with continuous asymmetrical gene flow from F. aquilonia to F. polyctena until a recent time, when migration became negligible (2–19 kya). However, we found support for contemporary gene flow in a sympatric pair from Finland, where the species hybridise, but no signature of recent bidirectional gene flow elsewhere. Overall, our results suggest that divergence histories reconstructed from a few individuals may be applicable at the species level. Nonetheless, the geographical context of populations chosen to represent their species should be taken into account, as it may affect estimates of migration rates between species when gene flow is spatially heterogeneous.
Home care providers' perceptions of shared decision‐making with older clients (and their caregivers): A cross‐sectional study
Authors: Lai Claudia , Holyoke Paul , Plourde Karine V. , Yeung Lily , Légaré France
Published: April 2022

Interprofessional care teams can play a key role in supporting older adults (and caregivers) in making informed health decisions, yet shared decision making is not widely practiced in home care. Based on an earlier needs assessment with older adults (and caregivers) with home care experience, we aimed to explore the perceptions of home care teams on the decisions facing their clients and their perceived involvement in shared decision making. A cross‐sectional study was conducted with 614 home care providers (nurses, personal support workers, rehabilitation professionals) in three Canadian provinces (Quebec, Ontario, and Alberta). Home care providers considered the decision “to stay at home or move” as the most difficult for older adults. Those most frequently involved in decision making with older adults were family members and least involved were physicians. Although all home care providers reported high levels of shared decision‐making, we detected an effect of respondent's discipline on self‐perceived shared decision‐making; nurses and rehabilitation professionals reported significantly higher levels of shared decision making than personal support workers. A more tailored approach is required to support shared decision making in interprofessional care teams.
Decoding the molecular regulation mechanism of plant architecture in woody plants
Authors: Liu Caixia , Chen Song , Wang Guohua , Chen Su
Published: April 2022

This article is a Commentary on Zheng et al. (2022), 235: 141–156.
Photobiomodulation for chemotherapy‐induced oral mucositis in leukemic children: A randomized controlled clinical trial
Authors: Reyad Farida A. , Elsayed Naguiba M , El Chazli Yasmine
Published: April 2022

Objectives

Evaluation of the effectiveness of Photobiomodulation(PBM) for chemotherapy‐induced oral mucositis (OM) in leukemic children.

Materials and methods

A randomized controlled clinical study including forty‐four leukemic children diagnosed with chemotherapy‐induced OM at the Hematology/Oncology inpatient unit at Alexandria University Children's Hospital, Alexandria, Egypt. Patients were randomly assigned to either the control or test groups with a 1:1 ratio. The control group received conventional symptomatic treatment, while the test group was treated with PBM in addition to the symptomatic treatment. The response to both treatment modalities was evaluated according to the reduction of pain and lesions severity from baseline to 5, 10, and 14 days after treatment.

Results

A significant reduction of pain was recorded on day 10 in the test group compared to the control group (p < 0.001). There was also a significant decline in the OM grades between the two groups on day14 (p = 0.003). No adverse events were reported.

Conclusions

The use of PBM along with the conventional treatment was effective in reducing pain and in the recovery of OM lesions in children receiving chemotherapy for the treatment of ALL. It was also safe and applicable to children.
Comprehensive analysis of microRNAs and their target genes in oral submucous fibrosis
Authors: Jishnu Padacherri Vethil , Shenoy Sangeetha U. , Sharma Mohit , Chopra Aditi , Radhakrishnan Raghu
Published: April 2022

The objective of the study is to understand the role of experimentally validated microRNAs (miRNAs) contributing to the acquisition of oncogenic phenotype in oral submucous fibrosis (OSF) by computational analysis. A comprehensive review was carried out to corroborate and summarize altered miRNA expression in OSF by retrieving relevant publications querying MEDLINE, Web of Science, Embase, and Scopus. The association between the miRNA‐mRNA was performed using miRTarBase 8.0. The visualization of the miRNA‐mRNA interaction was plotted using Cytoscape. MIENTURNET was used for the pathway analysis. Enrichment analysis was carried out for elucidating the hierarchical functions of miRNAs related to the acquisition of biological processes involved in the development of cancer. Thirteen miRNAs (hsa‐miR‐499a, hsa‐miR‐200b, hsa‐miR‐200c, hsa‐miR‐1246, hsa‐miR‐31, hsa‐miR‐10b, hsa‐miR‐21, hsa‐miR‐203, hsa‐miR‐455, hsa‐miR‐760, hsa‐miR‐623, hsa‐miR‐610, and hsa‐miR‐509‐3‐5p) were found to be deregulated in OSF. A total of 371 experimentally validated genes were shown to be interacting with the OSF‐associated miRNAs. The targets of antifibrotic and profibrotic miRNAs were enriched in the cancer‐related pathways. Dysregulated miRNA and its target genes illustrate the physiological role of miRNAs in fibrosis. Understanding the miRNA‐mediated fibrotic signaling and targetting the specific miRNA‐target gene interaction might provide relevant cues to ameliorate the fibrotic disease.
Trust, but verify? Understanding citizen attitudes toward evidence‐informed policy making
Authors: Bundi Pirmin , Pattyn Valérie
Published: April 2022

In this article, we inquire to what extent different manifestations of trust are associated with public support for evidence informed policy making (EIPM). We present the results of a cross‐sectional survey conducted in the peak of the second COVID‐19 wave in six Western democracies: Australia, Belgium, Canada, France, Switzerland, and the United States (N = 8749). Our findings show that public trust in scientific experts is generally related to positive attitudes toward evidence‐informed policy making, while the opposite is the case for trust in governments and fellow citizens. Interestingly, citizens' assessment of government responses to COVID‐19 moderates the relationship between trust and attitudes toward EIPM. Respondents who do rather not trust their governments or their fellow citizens are more in favor of EIPM if they evaluate government responses negatively. These findings suggest that attitudes toward EIPM are not only related to trust, but also strongly depend on perceived government performance.