bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Mandatory Auditor Tenure Disclosures on Ratification Voting, Auditor Dismissal, and Audit Pricing*
Authors: Dunn Ryan T. , Lundstrom Nathan G. , Wilkins Michael S.
Published: June 2021

Recent amendments to Auditing Standard (AS) 3101 require disclosure of the initial year of the auditor‐client relationship in the audit report. As the standard was being discussed, auditors, clients, and some PCAOB members expressed reservations about the necessity of tenure disclosures and were particularly concerned about disclosing tenure in the audit report. Our purpose is to investigate whether the tenure disclosures mandated by AS 3101 are associated with changes in stakeholder behavior. We predict and find that after the implementation date, ratification votes against the auditor and the probability of subsequent auditor dismissal increase for long‐tenured versus short‐tenured auditors. Results from a path analysis further suggest that the relative increase in dismissal for long‐tenured auditors appears to be influenced directly through tenure disclosures and indirectly through ratification voting. We also predict and find that negotiating power decreases for long‐tenured auditors as evidenced by lower audit fees. Our results are comparable for companies that voluntarily disclosed and companies that did not disclose auditor tenure in their proxy statements prior to the AS 3101 amendment. Overall, our study suggests that mandatory disclosure of auditor tenure in the audit report significantly affects stakeholder behavior. The PCAOB should consider our findings carefully as they evaluate whether AS 3101 is achieving its intended purpose.
Oral health status of newly admitted residents living in residential aged care
Authors: Chu K‐Y , Cockrell D , Naganathan V , Stanaway F , Wright FAC
Published: June 2021

Background

It is important to understand whether older people are admitted into residential care with existing dental diseases or their oral health deteriorates while residing in residential care. There is, however, little research available exploring the oral health status of people newly admitted into residential care. Understanding this disease trend would lead to effective prevention and treatment strategies to be trialled and implemented prior to admission. In this cross‐sectional study, we hypothesize that older people with one or more natural teeth might have poor oral health prior to admission to residential care.

Method

The study was carried out using the de‐identified oral health assessment database of an established domiciliary oral health care program in metropolitan New South Wales, Australia. Four hundred and nine participants with mean participant age of 85.56 years from 13 facilities from 2015 to 2018 fulfilled the inclusion criteria for this study.

Conclusion

This study confirmed that dentate, newly admitted residents to residential care had pre‐existing dental problems and oral health concerns. Almost half of the newly admitted residents had an unsatisfactory oral cleanliness score when examined in their residential care setting.
Decompression strategy for critical‐sized lesions: A case series and literature review
Authors: Umer Fahad , Javed Faizan
Published: June 2021

Critical‐sized lesions are defined as the smallest sized intraosseous wound in a particular bone that will not heal spontaneously during the lifetime of that animal. These critical‐sized entities pose a unique challenge in endodontics, where these lesions are most likely cystic, with dimensions extending over 10 mm. This paper describes a structured methodology to treat such cases whilst also highlighting inconsistencies and variability between practitioners regarding management of critical‐sized lesions. The case series demonstrates that non‐surgical root canal therapy followed by surgical decompression may be the treatment of choice for such pathosis. A 16 gauge nasogastric tube was used as a decompression device and sutured to surrounding mucosa. Healing was evaluated using both two‐ and three‐dimensional radiographs. Decompression of critical‐sized lesions would appear to be a reliable, conservative and an altogether complete procedure that may not warrant second‐stage surgery.
3D reconstruction of the rat adrenal medulla
Authors: Kemoklidze Konstantin Gerbertovich , Tyumina Natalia Andreevna , Leonenko Pavel Sergeevich
Published: June 2021

We performed 3D reconstruction of the microscopic structure of the adrenal medulla of the adult rats using serial histological sections with histochemical differentiation of adrenaline‐storing (A) and noradrenaline‐storing (NA) cells. Medulla volume is 1.18 ± 0.17 mm3. Chromaffin tissue consists of 82.9 ± 2.6% of A and 17.1 ± 2.6% of NA cells. Cords of the chromaffinocytes run along the nerves in the adrenal cortex and form cones when merging with medulla bulk. There is no unambiguously greater prevalence of A cells over NA in the areas of the medulla bordering on the cortex as compared to deep layers of medulla. NA cells form a network of beams. Their concentration increases with distance from the entry site of the nerves and is maximal on the opposite side. This testifies to the fallacy of the point of view about the disordered distribution of NA cells in the medulla. Based on the polar asymmetric arrangement of the adrenal chromaffin tissue, if it is necessary to completely remove the medulla with the keeping or reimplantation of the cortex, the subcapsular cortex zone located on the pole opposite to the entrance of nerves should be chosen. In addition, comparable results in the stereological examination of the medulla can be obtained only if taking its areas similar in location. The pronounced relationship in the arrangement of A and NA cells with nerves clearly indicates that in vivo nerve factors play a key role in differentiation and stabilization of the A and NA cells phenotypes.
How rural nurses in Southern New Zealand navigate their ethical landscape—A qualitative study
Authors: Doolan‐Noble Fiona , Tumilty Emma , McAuley Kathryn , Stokes Tim
Published: June 2021

Objective

To explore rural nurse experiences of ethical issues and their management of these as a first step in a programme of work to address rural nurses' ethical needs.

Design

This study was qualitative, using mixed qualitative techniques to gather data, which was analysed using a general inductive approach.

Setting

Primary health care in 2 regions of Aotearoa New Zealand.

Participants

Eleven nurses working in the West Coast (District Health Board) region and 9 working within the Southern District Health Board region.

Intervention

Participants took part in either a focus groups or an interview with members of the research team.

Main outcome measures

To document ethical issues that confronted these rural nurses and how they navigated these issues.

Results

Three themes were identified: ‘Signals and Silences,’ ‘One and Other’ and ‘Frustrations and Freedoms.’ A continuous thread through these themes was the concept of phronesis, or what is sometimes called practical virtue. This practical virtue largely developed through their own experiences, rather than through educational or health system specific support or resources.

Conclusions

We found that rural nurses' deal with specific issues related to the rural setting, such as resourcing and isolation, while maintaining a relationship with the communities they serve and their professional autonomy. Additionally, we discovered the ways in which rural nurses deal with the ethical issues they encounter to be practically focussed. However, rural nurses need supportive leadership not only to sustain the moral agency they demonstrate but also to further develop their ethical decision‐making practices. The provision of a clinical ethics tele‐service delivering both training opportunities and an on‐call consult support service would provide a potential solution.
Mother‐Newborn Couplet Care from theory to practice to ensure zero separation for all newborns
Authors: Klemming Stina , Lilliesköld Siri , Westrup Björn
Published: June 2021

With an increasing awareness of the importance of nurturing care and within a framework of Infant‐ and Family‐Centred Developmental Care (IFCDC), zero separation, keeping parent and infant in continuous close physical and psychological proximity to each other, is key. In modern neonatology, high technological and pharmaceutical treatments are consistently integrated with caregiving considerations. Mother‐Newborn Couplet Care is a concept of care where the dyad of the ill or prematurely born infant and the mother, needing medical care of her own, are cared for together, from the birth of the baby to its discharge. Mother‐Newborn Couplet Care requires systems changes in both obstetrics and paediatrics considering planning and organisation of care, equipment and design of units. Accordingly, strong leadership setting clear goals and changing the professional mindset by providing targeted education and training is crucial to ensure the warranted high quality of care of all mother‐baby dyads.
3‐Quinuclidinyl benzilate (agent BZ) toxicokinetics in rats
Authors: Dlabkova Alzbeta , Herman David , Cechova Lenka , Hroch Milos , Vanova Nela , Zdarova Karasova Jana
Published: June 2021

3‐Quinuclidinyl benzilate (BZ) ranks among incapacitating military warfare agents. It acts as a competitive inhibitor on muscarinic receptors leading to non‐lethal mental impairment. The present study aimed to investigate toxicokinetics of BZ in rats. Moreover, BZ can be exploited to produce a pharmacological model of Alzheimer's disease; thus, this paper focuses mainly on the BZ distribution to the brain. Wistar rats were administered i.p. with BZ (2 and 10 mg/kg). The BZ concentration was determined using LC‐MS/MS in plasma, urine, bile, brain, kidney and liver. The sample preparation was based on a solid phase extraction (liquids) or protein precipitation (organ homogenates). The plasma concentration peaked at 3 min (204.5 ± 55.4 and 2185.5 ± 465.4 ng/ml). The maximal concentration in the brain was reached several minutes later. Plasma elimination half‐life was 67.9 ± 3.4 in the 2 mg/kg group and 96.6 ± 27.9 in the 10 mg/kg group. BZ concentrations remained steady in the brain, with slow elimination (t1/2 506.9 ± 359.5 min). Agent BZ is excreted mainly via the urine. Steady BZ concentration in the brain could explain the previously published duration of the significant impairment in passive avoidance tasks in rats after an injection of BZ.
Dark times for cosmopolitanism? An ethical framework to address private agri‐food governance and planetary stewardship
Authors: Alcaraz Jose M. , Tirado Francisco , Gálvez Ana
Published: June 2021

The scholarly tradition of cosmopolitanism (illustrated by the old saying, “I am a citizen of the world”) offers important insights into the examination of agri‐food multinational corporations (MNCs) as powerful global actors. Acknowledging that agriculture is the business sector with the highest planetary environmental impact, in this paper, we advance existing discussions around cosmopolitanism and the normative implications of considering agri‐food MNCs as political actors. Relying on an integrative literature review, we propose a tripartite ethical framework that gives a new momentum to the ideals and tenets of cosmopolitanism. This novel lens offers an integrated, seamless ethical approach and revolves around three dimensions:culture,morality, andgovernance. The first dimension examines key agri‐food cultural and social‐ecological issues, the second acknowledges interdependence and causality as central to understanding MNCs’ ethical responsibilities, and the third outlines several governance parameters around legitimacy, planetary reach and efficiency. Hence, our integrative framework resituates the planetary geographical imagination of cosmopolitanism within the biophysical parameters outlined by the planetary boundaries concept, advancing key issues on private agri‐food environmental governance and planetary stewardship.
I’ll scratch your back if you give me a compliment: Exploring psychological mechanisms underlying compliments’ effects on compliance
Authors: Grant Naomi K. , Krieger Laura R. , Nemirov Harrison , Fabrigar Leandre R. , Norris Meghan E.
Published: June 2021

Although compliments can be an effective compliance tactic, little is known about the reasons for their effectiveness. Two studies tested three potential mechanisms underlying the use of compliments as a compliance tactic: reciprocity, positive mood, and liking. In both studies, participants were either primed with the reciprocity norm or not, then received either complimentary or neutral feedback from a stranger. Participants were later faced with a request from the stranger. Mood, liking for the requestor, and compliance were measured. As predicted, compliments increased compliance in both studies. Neither study found evidence for positive mood nor liking as a mediator of the compliment effect. However, reciprocity priming was found to moderate the compliment effect in both studies, suggesting that compliments are effective, at least in part, because they invoke the reciprocity norm.
Thy will be done: Exploring the longitudinal rewards of religious group membership enactment during volunteering
Authors: Wakefield Juliet Ruth Helen , Bowe Mhairi , Kellezi Blerina
Published: June 2021

The volunteering literature is replete with studies revealing the health benefits of volunteering. This has led psychologists to question whether social processes may help deliver these benefits while also supporting sustained volunteering engagement. The Social Identity Approach (SIA) recognizes that volunteering takes place in groups and sheds light on these processes by providing insights into group dynamics. Specifically, recent work within the Social Cure tradition has revealed the dynamic relationship between volunteering and group identification, and how this can influence health and well‐being. This study extends previous work by exploring whether the relationship is mediated by the extent to which volunteers feel able to enact their membership of a valued group (specifically their religious group) through their volunteering. People who volunteer with religiously motivated voluntary groups (N = 194) completed the same online survey twice, three months apart (T1/T2). For participants high in religiosity, T1 identification with their voluntary group positively predicted their sense of being able to enact the membership of their religious group through their voluntary work at T2, which in turn was a positive predictor of T2 mental health and volunteer engagement. The implications of these findings for both the theoretical literature and for voluntary organizations are discussed.
Trametinib overcomes KRAS‐G12V–induced osimertinib resistance in a leptomeningeal carcinomatosis model of EGFR‐mutant lung cancer
Authors: Fukuda Koji , Otani Sakiko , Takeuchi Shinji , Arai Sachiko , Nanjo Shigeki , Tanimoto Azusa , Nishiyama Akihiro , Naoki Katsuhiko , Yano Seiji
Published: June 2021

Leptomeningeal carcinomatosis (LMC) occurs frequently in non–small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and is associated with acquired resistance to EGFR tyrosine kinase inhibitors (EGFR‐TKIs). However, the mechanism by which LMC acquires resistance to osimertinib, a third‐generation EGFR‐TKI, is unclear. In this study, we elucidated the resistance mechanism and searched for a novel therapeutic strategy. We induced osimertinib resistance in a mouse model of LMC using an EGFR‐mutant NSCLC cell line (PC9) via continuous oral osimertinib treatment and administration of established resistant cells and examined the resistance mechanism using next‐generation sequencing. We detected the Kirsten rat sarcoma (KRAS)‐G12V mutation in resistant cells, which retained the EGFR exon 19 deletion. Experiments involving KRAS knockdown in resistant cells and KRAS‐G12V overexpression in parental cells revealed the involvement of KRAS‐G12V in osimertinib resistance. Cotreatment with trametinib (a MEK inhibitor) and osimertinib resensitized the cells to osimertinib. Furthermore, in the mouse model of LMC with resistant cells, combined osimertinib and trametinib treatment successfully controlled LMC progression. These findings suggest a potential novel therapy against KRAS‐G12V–harboring osimertinib‐resistant LMC in EGFR‐mutant NSCLC.
Novel metastatic burden‐stratified risk model in de novo metastatic hormone‐sensitive prostate cancer
Authors: Shiota Masaki , Terada Naoki , Kitamura Hiroshi , Kojima Takahiro , Saito Toshihiro , Yokomizo Akira , Kohei Naoki , Goto Takayuki , Kawamura Sadafumi , Hashimoto Yasuhiro , Takahashi Atsushi , Kimura Takahiro , Tabata Ken‐ichi , Tomida Ryotaro , Hashimoto Kohei , Sakurai Toshihiko , Shimazui Toru , Sakamoto Shinichi , Kamiyama Manabu , Tanaka Nobumichi , Mitsuzuka Koji , Kato Takuma , Narita Shintaro , Yasumoto Hiroaki , Teraoka Shogo , Kato Masashi , Osawa Takahiro , Nagumo Yoshiyuki , Matsumoto Hiroaki , Enokida Hideki , Sugiyama Takayuki , Kuroiwa Kentaro , Inoue Takahiro , Sugimoto Mikio , Mizowaki Takashi , Kamoto Toshiyuki , Nishiyama Hiroyuki , Eto Masatoshi ,   Japanese Urological Oncology Group
Published: June 2021

The metastatic burden is a critical factor for decision‐making in the treatment of metastatic hormone‐sensitive prostate cancer (HSPC). This study aimed to develop and validate a novel risk model for survival in patients with de novo low‐ and high‐burden metastatic HSPC. The retrospective observational study included men with de novo metastatic prostate cancer who were treated with primary androgen‐deprivation therapy at 30 institutions across Japan between 2008 and 2017. We created a risk model for overall survival (OS) in the discovery cohort (n = 1449) stratified by the metastatic burden (low vs high) and validated its predictive ability in a separate cohort (n = 951). Based on multivariate analyses, lower hemoglobin levels, higher Gleason grades, and higher clinical T‐stage were associated with poor OS in low‐burden disease. Meanwhile, lower hemoglobin levels, higher Gleason grade group, liver metastasis, and higher extent of disease scores in bone were associated with poor OS in patients with high‐burden disease. In the discovery and validation cohorts, the risk model using the aforementioned parameters exhibited excellent discriminatory ability for progression‐free survival and OS. The predictive ability of this risk model was superior to that of previous risk models. Our novel metastatic burden‐stratified risk model exhibited excellent predictive ability for OS, and it is expected to have several clinical uses, such as precise prognostic estimation.
Beneficiaries of radical surgery among clinical complete responders to neoadjuvant chemoradiotherapy in rectal cancer
Authors: Zhang Shu , Zhang Rong , Li Rong‐zhen , Wang Qiao‐xuan , Chang Hui , Ding Pei‐rong , Li Li‐ren , Wu Xiao‐jun , Chen Gong , Zeng Zhi‐fan , Xiao Wei‐wei , Gao Yuan‐hong
Published: June 2021

This study aimed to identify patients who benefit from radical surgery among those with rectal cancer who achieved clinical complete response (cCR). Patients with locally advanced rectal cancer (LARC; stage II/III) who achieved cCR after neoadjuvant chemoradiotherapy (nCRT) were included (n = 212). Univariate/multivariate Cox analysis was performed to validate predictors for distant metastasis‐free survival (DMFS). A decision tree was generated using recursive partitioning analysis (RPA) to categorize patients into different risk stratifications. Total mesorectal excision (TME) was compared with the watch‐and‐wait (W&W) strategy in each risk group. Two molecular predicators of CEA and CA19‐9 were selected to establish the RPA‐based risk stratification, categorizing LARC patients into low‐risk (n = 139; CA19‐9 < 35 U/mL and CEA < 5 ng/mL) and high‐risk (n = 73; CA19‐9 ≥ 35 U/mL or CEA ≥5 ng/mL) groups. Superior 5‐y DMFS was observed in the low‐risk group vs. the high‐risk group (92.9% vs. 76.2%, P = .002). Low‐risk LARC patients who underwent TME had significantly improved 5‐y DMFS compared with their counterparts receiving the W&W strategy (95.9% vs. 84.3%; P = .028). No significant survival difference was observed in high‐risk patients receiving the 2 treatment modalities (77.9% vs. 94.1%; P = .143). LARC patients with cCR who had both baseline CA19‐9 < 35 U/mL and CEA < 5 ng/mL may benefit from radical surgery.
Alginate oligosaccharide alleviates senile osteoporosis via the RANKL–RANK pathway in D‐galactose‐induced C57BL/6J mice
Authors: Wang Shan , Feng Wenjing , Liu Jianya , Wang Xufu , Zhong Lina , Lv Chengxiu , Feng Meiping , An Nina , Mao Yongjun
Published: June 2021

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density (BMD) and bone quality and increased bone porosity, which increase the risk of bone fracture. Inflammation, one of the important mechanisms related to aging, is associated with osteoporosis. Treatment with anti‐inflammatory agents is effective for alleviating senile osteoporosis. Alginate oligosaccharide (AOS) can prevent and treat diseases related to inflammation, oxidative stress, and immunity. This study evaluates the effect of AOS on osteoporosis and investigates the underlying mechanism. Osteoporosis model was induced by D‐galactose (D‐gal) (200 mg kg−1 day−1) for eight weeks. Three groups were administered via AOS (50, 100, and 150 mg kg−1 day−1) for four weeks, while a control group received sterile water (5 ml kg−1 day−1) for 8 weeks. The results showed that AOS improved bone density and bone microstructure in D‐gal‐induced osteoporosis mice. AOS inhibited osteoclast proliferation, probably through the suppression of receptor activator of nuclear factor‐kappa B ligand (RANKL)‐associated nuclear factor kappa B (NF‐κB) and c‐Fos signaling pathway. AOS also increased osteoprotegerin (OPG) expression and competitively inhibited the binding between RANK and RANKL in senile osteoporosis. Further, AOS decreased the secretion of serum osteocalcin and reduced bone conversion. Together, these results demonstrate the anti‐osteoporosis activity of AOS in mice with osteoporosis.
Cytometric analysis of T cell phenotype using cytokine profiling for improved manufacturing of an EBV-specific T cell therapy
Authors: Cooper Rachel S , Kowalczuk Aleksandra , Wilkie Gwen , Vickers Mark A , Turner Marc L , Campbell John D M , Fraser Alasdair R
Published: June 2021

Adoptive immunotherapy using Epstein–Barr Virus (EBV)-specific T cells is a potentially curative treatment for patients with EBV-related malignancies where other clinical options have proved ineffective. We describe improved good manufacturing practice (GMP)-compliant culture and analysis processes for conventional lymphoblastoid cell line (LCL)-driven EBV-specific T cell manufacture, and describe an improved phenotyping approach for analysing T cell products. We optimized the current LCL-mediated clinical manufacture of EBV-specific T cells to establish an improved process using xenoprotein-free GMP-compliant reagents throughout, and compared resulting products with our previous banked T cell clinical therapy. We assessed effects of changes to LCL:T cell ratio in T cell expansion, and developed a robust flow cytometric marker panel covering T cell memory, activation, differentiation and intracellular cytokine release to characterize T cells more effectively. These data were analysed using a t-stochastic neighbour embedding (t-SNE) algorithm. The optimized GMP-compliant process resulted in reduced cell processing time and improved retention and expansion of central memory T cells. Multi-parameter flow cytometry determined the optimal protocol for LCL stimulation and expansion of T cells and demonstrated that cytokine profiling using interleukin (IL)-2, tumour necrosis factor (TNF)-α and interferon (IFN)-γ was able to determine the differentiation status of T cells throughout culture and in the final product. We show that fully GMP-compliant closed-process culture of LCL-mediated EBV-specific T cells is feasible, and profiling of T cells through cytokine expression gives improved characterization of start material, in-process culture conditions and final product. Visualization of the complex multi-parameter flow cytometric data can be simplified using t-SNE analysis.
Pharmacogenetic variants of infliximab response in young patients with inflammatory bowel disease
Authors: Curci Debora , Lucafò Marianna , Cifù Adriana , Fabris Martina , Bramuzzo Matteo , Martelossi Stefano , Franca Raffaella , Decorti Giuliana , Stocco Gabriele
Published: June 2021

Infliximab is commonly used in inflammatory bowel disease (IBD), however, differences in clinical response among patients are common. Several studies have considered the possibility that these differences are caused by genetic variability even if no unique marker has been yet identified in pediatric patients. We evaluated the impact of two candidate single‐nucleotide polymorphisms (SNPs) rs396991 in FCGR3A and rs1800629 in TNFα genes on infliximab response in an Italian cohort of 76 pediatric patients with IBD. Results showed that patients with the variant FCGR3A allele had a reduced clinical response at the end of induction (p value = 0.004), at 22 weeks (p value = 0.001), and at 52 weeks of treatment (p value = 0.01). A significant association between the FCGR3A variant and median infliximab levels measured during maintenance therapy was also observed: patients with wild type genotype had higher infliximab levels compared to patient with variant allele. Furthermore, patients with the variant allele had a higher probability to produce antidrug antibodies (ADAs). No association was found among the TNFα SNP, clinical response, and infliximab levels. This study addressed for the first time in pediatric patients with IBD, the association of FCGR3A SNP, infliximab response, and ADA production.
The Dyskinetic Cerebral Palsy Functional Impact Scale: development and validation of a new tool
Authors: Stewart Kirsty , Lewis Jennifer , Wallen Margaret , Bear Natasha , Harvey Adrienne
Published: June 2021

Aim

To outline the development and examine the content and construct validity of a new tool, the Dyskinetic Cerebral Palsy Functional Impact Scale (D‐FIS), which measures the impact of dyskinesia on everyday activities in children with cerebral palsy (CP).

Method

D‐FIS content was informed by a systematic review of dyskinesia outcome measures, in collaboration with children with dyskinetic CP, parents, caregivers, and expert clinicians. The D‐FIS uses parent proxy to rate impact of dyskinesia on everyday activities. Construct validity was determined by examining internal consistency; known groups validity with the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), Communication Function Classification System (CFCS), and Eating and Drinking Ability Classification System (EDACS); and convergent validity with the Barry‐Albright Dystonia Scale (BADS).

Results

Fifty‐seven parents of children (29 males, 28 females, mean [SD] age 11y 8mo [4y 4mo], range 2y 6mo–18y) completed the D‐FIS. Correlation between D‐FIS and GMFCS was r=0.86 (95% confidence interval [CI]: 0.77–0.91, p<0.001); MACS r=0.84 (95% CI: 0.73–0.90, p<0.001); CFCS r=0.80 (95% CI: 0.67–0.88, p<0.001); and EDACS r=0.78 (95% CI: 0.66–0.87). Correlation between D‐FIS and BADS was r=0.77 (95% CI: 0.64–0.86, p<0.001). Cronbach’s alpha was 0.96.

Interpretation

The D‐FIS demonstrates good construct validity and high internal consistency. The D‐FIS will be useful for identifying priorities for intervention. It adds to the measurement tool kit for children with dyskinetic CP by addressing functional impact of dyskinetic movements and postures.

What this paper adds

The Dyskinetic Cerebral Palsy Functional Impact Scale (D‐FIS) assesses the perceived impact of dyskinesia on daily activities in children with cerebral palsy (CP).

The D‐FIS demonstrates good construct validity and high internal consistency.

The D‐FIS is a clinically feasible, family‐centred tool that fills a current gap in the dyskinetic CP assessment toolkit.
Building a competitive infrastructure to support clinical research in healthcare institution
Authors: Cimino Jonathan , Braun Claude
Published: June 2021

Background

Clinical research is becoming increasingly popular in Europe at a growth rate much higher than expected, especially in Benelux. Although traditionally thought to be the purview of academic health centres, clinical research to evaluate new drugs, devices and medical practices is being done more and more in healthcare organizations with little or no academic affiliation.

Methods

By managing a new infrastructure and centralizing resources and demands, clinical research unit (CRU) has become an effective mechanism for hospital research. The ‘infrastructure’ or CRU refers to the necessary resources and how the CRU is organized and communicates operationally to conduct clinical research within the institution. The creation of a new CRU within the Robert Schuman Hospital in Luxembourg is described in this article.

Results

This article discusses the concrete steps and basic elements such as patient‐centric and hospital approaches needed to create and structure a CRU to provide academic or industry‐sponsored research support in clinical research.

Conclusions

Some infrastructure challenges (insufficient engagement, regulatory and administrative barriers) and possible courses of action (standardized procedures, training and centralization) will be discussed.
Exploring spatial ability in healthcare students and the relationship to training with virtual and actual objects
Authors: Sezer Baris , Sezer Tufan Asli , Elcin Melih
Published: June 2021

Introduction

The relationship between the spatial ability levels of students and anatomy education is not well established in the literature, but it was stated that students should take short‐term training during the first years of their education. There is limited number of studies on this topic. In that respect, the aim of this study was to determine the spatial ability levels of medical, dental and nursing students and to evaluate whether this ability level showed difference with respect to faculty, anatomy courses attended or short‐term training, or not.

Materials and Methods

Study sample was composed of 1071 students. Data were collected by Personal Information Form, Visualization of Views Test (VoVT) and Cross Section Test (CST). Data analyses were done by SPSS 21 package software.

Results

Students were determined to have medium level spatial ability. Medical and dental students were found to have higher spatial ability levels than nursing students. Medical and nursing students’ CST scores showed significant difference after taking anatomy course. After short‐term training, both CST and VoVT scores of students differed significantly.

Conclusion

Supporting anatomy courses with education materials appropriate for the spatial ability level of students and introducing spatial ability development trainings in small groups would aid in increasing spatial ability levels of students.
EBI2 is expressed in glial cells in multiple sclerosis lesions, and its knock‐out modulates remyelination in the cuprizone model
Authors: Klejbor Ilona , Shimshek Derya R. , Klimaszewska‐Łata Joanna , Velasco‐Estevez Maria , Moryś Janusz , Karaszewski Bartosz , Szutowicz Andrzej , Rutkowska Aleksandra
Published: June 2021

EBI2 receptor regulates the immune system, and in multiple, sclerosis is upregulated in the central nervous system infiltrating lymphocytes. In newborn EBI2‐deficient mice, myelin development is delayed, and its persistent antagonism inhibits remyelination in chemically demyelinated organotypic cerebellar slices. We used the cuprizone model of multiple sclerosis to elucidate the role of central nervous system‐expressed EBI2 in de‐ and remyelination. The wild‐type and EBI2 knock‐out mice were fed 0.2% cuprizone in chow for 5 weeks and allowed to recover on a normal diet for 2 weeks. The data showed less efficient recovery of myelin, attenuated oligodendrocyte loss, fewer astrocytes and increased total cholesterol levels in the EBI2 knock‐out mice after recovery. Moreover, the wild‐type mice upregulated EBI2 expression after recovery confirming the involvement of EBI2 signalling during recovery from demyelination in the cuprizone model. The pro‐inflammatory cytokine levels were at comparable levels in the wild‐type and EBI2 knock‐out mice, with only minor differences in TNFα and IL1β levels either at peak or during recovery. The neuroinflammatory signalling molecules, Abl1 kinase and NFКB1 (p105/p50) subunit, were significantly downregulated in the EBI2 knock‐out mice at peak of disease. Immunohistochemical investigations of EBI2 receptor distribution in the central nervous system (CNS) cells in multiple sclerosis (MS) brain revealed strong expression of EBI2 in astrocytes and microglia inside the plaques implicating glia‐expressed EBI2 in multiple sclerosis pathophysiology. Taken together, these findings demonstrate the involvement of EBI2 signalling in the recovery from demyelination rather than in demyelination and as such warrant further research into the role of EBI2 in remyelination.
No evidence for a single oscillator underlying discrete visual percepts
Authors: Morrow Audrey , Samaha Jason
Published: June 2021

Theories of perception based on discrete sampling posit that visual consciousness is reconstructed based on snapshot‐like perceptual moments, as opposed to being updated continuously. According to a model proposed by Schneider (2018), discrete sampling can explain both the flash–lag and the Fröhlich illusion, whereby a lag in the conscious updating of a moving stimulus alters its perceived spatial location in comparison to stationary stimulus. The alpha‐band frequency, which is associated with phasic modulation of stimulus detection and the temporal resolution of perception, has been proposed to reflect the duration of perceptual moments. The goal of this study was to determine whether a single oscillator (e.g., alpha) is underlying the duration of perceptual moments, which would predict that the point of subjective equality (PSE) in the flash–lag and Fröhlich illusions are positively correlated across individuals. Although our displays induced robust flash–lag and Fröhlich effects, virtually zero correlation was seen between the PSE in the two illusions, indicating that the illusion magnitudes are unrelated across observers. These findings suggest that, if discrete sampling theory is true, these illusory percepts either rely on different oscillatory frequencies or not on oscillations at all. Alternatively, discrete sampling may not be the mechanism underlying these two motion illusions or our methods were ill‐suited to test the theory.
Neural correlates of visual stimulus encoding and verbal working memory differ between cochlear implant users and normal‐hearing controls
Authors: Prince Priyanka , Paul Brandon T. , Chen Joseph , Le Trung , Lin Vincent , Dimitrijevic Andrew
Published: June 2021

A common concern for individuals with severe‐to‐profound hearing loss fitted with cochlear implants (CIs) is difficulty following conversations in noisy environments. Recent work has suggested that these difficulties are related to individual differences in brain function, including verbal working memory and the degree of cross‐modal reorganization of auditory areas for visual processing. However, the neural basis for these relationships is not fully understood. Here, we investigated neural correlates of visual verbal working memory and sensory plasticity in 14 CI users and age‐matched normal‐hearing (NH) controls. While we recorded the high‐density electroencephalogram (EEG), participants completed a modified Sternberg visual working memory task where sets of letters and numbers were presented visually and then recalled at a later time. Results suggested that CI users had comparable behavioural working memory performance compared with NH. However, CI users had more pronounced neural activity during visual stimulus encoding, including stronger visual‐evoked activity in auditory and visual cortices, larger modulations of neural oscillations and increased frontotemporal connectivity. In contrast, during memory retention of the characters, CI users had descriptively weaker neural oscillations and significantly lower frontotemporal connectivity. We interpret the differences in neural correlates of visual stimulus processing in CI users through the lens of cross‐modal and intramodal plasticity.
Interplay of population size and environmental fluctuations: A new explanation for fitness cost rarity in asexuals
Authors: Chavhan Yashraj , Malusare Sarthak , Dey Sutirth
Published: June 2021

Theoretical models of ecological specialisation commonly assume that adaptation to one environment leads to fitness reductions (costs) in others. However, experiments often fail to detect such costs. We addressed this conundrum using experimental evolution with Escherichia coli in several constant and fluctuating environments at multiple population sizes. We found that in fluctuating environments, smaller populations paid significant costs, but larger ones avoided them altogether. Contrastingly, in constant environments, larger populations paid more costs than the smaller ones. Overall, large population sizes and fluctuating environments led to cost avoidance only when present together. Mutational frequency distributions obtained from whole‐genome whole‐population sequencing revealed that the primary mechanism of cost avoidance was the enrichment of multiple beneficial mutations within the same lineage. Since the conditions revealed by our study for avoiding costs are widespread, it provides a novel explanation of the conundrum of why the costs expected in theory are rarely detected in experiments.
Muscle involvement assessed by quantitative magnetic resonance imaging in patients with anoctamin 5 deficiency
Authors: Khawajazada Tahmina , Kass Konni , Rudolf Karen , de Stricker Borch Josefine , Sheikh Aisha Munawar , Witting Nanna , Vissing John
Published: June 2021

Objective

Using magnetic resonance imaging (MRI) and stationary dynamometry, the aim was to investigate the muscle affection in paraspinal muscles and lower extremities and compare the muscle affection in men and women with anoctamin 5 (ANO5) deficiency.

Methods

Seventeen patients (seven women) with pathogenic ANO5‐mutations were included. Quantitative muscle fat fraction of back and leg muscles were assessed by Dixon MRI. Muscle strength was assessed by stationary dynamometer. Results were compared with 11 matched, healthy controls.

Results

Muscle involvement pattern in men with ANO5‐deficiency is characterized by a severe fat replacement of hamstrings, adductor and gastrocnemius muscles, while paraspinal muscles are only mildly affected, while preserved gracilis and sartorius muscles were hypertrophied. Women with ANO5‐myopathy, of the same age as male patients, were very mildly affected, showing muscle affection and strength resembling that found in healthy persons, with the exception of the gluteus minimus and medius and gastrocnemii muscles that were significantly replaced by fat. Although individual muscles showed clear asymmetric involvement in a few muscle groups, the overall muscle involvement was symmetric.

Conclusions

Patients with ANO5‐deficiency have relatively preserved paraspinal muscles on imaging and only mild reduction of trunk extension strength in men only. Our study quantifies the large difference in muscle affection in lower extremity between women and men with ANO5‐deficiency. The clinical notion is that affection may be very asymmetric in ANO5‐deficiency, but the present study shows that while this may be true for a few muscles, the general impression is that muscle affection is very symmetric.
Indoleamine 2,3‐dioxygenase 1 (IDO1): an up‐to‐date overview of an eclectic immunoregulatory enzyme
Authors: Pallotta Maria Teresa , Rossini Sofia , Suvieri Chiara , Coletti Alice , Orabona Ciriana , Macchiarulo Antonio , Volpi Claudia , Grohmann Ursula
Published: June 2021

Indoleamine 2,3‐dioxygenase 1 (IDO1) catalyzes the initial rate‐limiting step in the degradation of the essential amino acid tryptophan along the kynurenine pathway. When discovered more than 50 years ago, IDO1 was thought to be an effector molecule capable of mediating a survival strategy based on the deprivation of bacteria and tumor cells of the essential amino acid tryptophan. Since 1998, when tryptophan catabolism was discovered to be crucially involved in the maintenance of maternal T‐cell tolerance, IDO1 has become the focus of several laboratories around the world. Indeed, IDO1 is now considered as an authentic immune regulator not only in pregnancy, but also in autoimmune diseases, chronic inflammation, and tumor immunity. However, in the last years, a bulk of new information—including structural, biological, and functional evidence—on IDO1 has come to light. For instance, we now know that IDO1 has a peculiar conformational plasticity and, in addition to a complex and highly regulated catalytic activity, is capable of performing a nonenzymic function that reprograms the expression profile of immune cells toward a highly immunoregulatory phenotype. With this state‐of‐the‐art review, we aimed at gathering the most recent information obtained for this eclectic protein as well as at highlighting the major unresolved questions.
Drop‐in ready jet biofuel from carinata: A real options analysis of processing plant investments
Authors: Zhao Chong , Colson Greg , Karali Berna , Philippidis George P.
Published: June 2021

A promising feedstock for large‐scale production of sustainable jet biofuel is the inedible oilseed Brassica carinata (referred to simply as “carinata”), but transitioning to large‐scale fuel production entails significant economic uncertainty and requires substantial up‐front capital requirements for biorefinery construction. Furthermore, for carinata and other feedstocks attempting to compete within the established fossil jet fuel market, historically volatile aviation fuel prices affect the economic feasibility and return of biorefinery investments. In this study, we assess the impact of jet fuel price volatility on the return on investment in a carinata biorefinery employing a real options analysis (ROA). The key advantage of ROA over traditional net present value (NPV) analysis is that it simultaneously assesses the optimal timing for investments and the impact of jet fuel price dynamics on the likelihood of positive economic returns from investments in processing plants. Given the nonstationary nature of jet fuel prices and the presence of structural breaks, the price series are modeled as a geometric Brownian motion. Taking into account the volatility of jet fuel price, the ROA price threshold for a profitable investment is 45% greater than the NPV threshold. The ROA model identifies the necessary market conditions for a profitable investment and highlights the importance of considering market price dynamics before making substantial capital investments in a carinata biorefinery.
Similar sports participation as the general population in Dutch persons with haemophilia; results from a nationwide study
Authors: Versloot Olav , van Balen Erna C. , Hassan Shermarke , Schols Saskia E.M. , Leebeek Frank W.G. , Eikenboom Jeroen , Coppens Michiel , van Vulpen Lize F.D. , Smit Cees , Driessens Mariëtte H.E. , van der Net Janjaap , Gouw Samantha C. , Fischer Kathelijn ,   the Haemophilia in the Netherlands 6 steering committee
Published: June 2021

Introduction

Although sports participation is advocated in people with haemophilia (PWH), detailed data concerning sports participation in Dutch PWH is lacking.

Aim

to assess sports participation in Dutch PWH (6‐65 years) compared to the Dutch general population (GP).

Methods

Data from a nationwide, cross‐sectional study in PWH were analysed. Sports participation (type, duration, frequency) was assessed by the Modifiable Activities Questionnaire (MAQ), limitations in activities using the (Paediatric) Haemophilia Activities List ((Ped)HAL). Sports in the two highest categories according to the National Hemophilia Foundation classification were considered high‐risk sports. Groups were compared using Chi‐square testing.

Results

A total of 524 Adult PWH (median age: 45 (IQR: 30–55); 37% severe) and 126 paediatric PWH (median age: 11 (IQR: 8–14); 52% severe) were included. Sports participation was higher in adults (70%) than the GP (58%) and similar to the GP in children (PWH: 68%, GP: 72%). High‐risk sports participation decreased with age in PWH: from 65% (6‐12 years) to 17% (50‐65 years), which was also observed in the GP. Sports participation in children was independent of severity (non‐severe: 67% vs. severe: 65%; P = 0.97), but not in adults (non‐severe: 75%, severe: 62%; P < 0.01). Non‐severe PWH played more high‐risk sports than severe PWH: children at 65% vs. 48% (P = 0.05), adults at 25% vs. 15% (P = 0.07).

Discussion

These results suggest that sports participation in PWH was comparable to the GP. Sports participation was dependent of haemophilia severity in adults. Children were more involved in high‐risk sports than adults. More studies on sports‐related injury‐risk are needed for adequate counselling.
VALUE PRESERVING WELFARE WEIGHTS FOR SOCIAL OPTIMIZATION PROBLEMS
Authors: Anagnostopoulos Alexis , Carceles‐Poveda Eva , Tauman Yair
Published: June 2021

We propose endogenous, value preserving (VP) welfare weights as an alternative to equal weights utilitarianism. VP weights require that the contribution of an agent's endowments to social welfare is proportional to the contribution of the final allocation to his welfare. Under three axioms, the per unit contribution of a good to welfare is shown to equal the gradient of the welfare function. VP weights coincide with Negishi weights in frictionless environments but prescribe redistribution toward a good's owner when the good's social value exceeds its market value. When ability is treated as an endowment, VP weights reward ability and effort.
Polymer (PCL) fibers with Zn‐doped mesoporous bioactive glass nanoparticles for tissue regeneration
Authors: Neščáková Zuzana , Kaňková Hana , Galusková Dagmar , Galusek Dušan , Boccaccini Aldo R. , Liverani Liliana
Published: June 2021

Composite fibrous membranes based on poly(ɛ‐caprolactone) (PCL) and mesoporous bioactive glass nanoparticles (MBGNs) were fabricated by electrospinning. MBGNs and Zn‐doped MBGNs prepared by microemulsion sol–gel method were successfully incorporated inside the polymeric fibers of 240 and 385 nm in diameter for undoped and Zn‐doped PCL_MBGNs fibers, respectively. Thermal analysis showed that the concentration of MBGNs reached a maximum of around 21 wt% for Zn‐doped MBGNs. Both PCL_MBGNs and PCL_MBGNs_Zn composite membrane exhibited bioactivity after immersion in simulated body fluid (SBF). X‐ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) showed the evolution of composite membranes, confirming the formation of hydroxyapatite (HAp). However, the degradation products of membranes did not affect the viability and proliferation of murine stromal cells (ST‐2) and thus the new fiber structures represent a suitable environment for cell adhesion. Therefore, the incorporation of mesoporous glass nanoparticles doped with therapeutically active Zn2+ ions inside the PCL fibers offers the possibility to create a multifunctional biomaterial suitable for drug delivery and tissue engineering.