bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicentre, prospective study on local treatment of metastatic prostate cancer (LoMP study)
Authors: Buelens Sarah , Poelaert Filip , Claeys Tom , De Bleser Elise , Dhondt Bert , Verla Wesley , Ost Piet , Rappe Bernard , De Troyer Bart , Verbaeys Caroline , Kimpe Bart , Billiet Ignace , Plancke Hendrik , Fransis Karen , Willemen Patrick , Ameye Filip , Decaestecker Karel , Lumen Nicolaas
Published: July 2021

Objectives

To investigate the role of cytoreductive radical prostatectomy in addition to standard of care for patients with newly diagnosed metastatic prostate cancer.

Materials and Methods

This multicentre, prospective study included asymptomatic patients from 2014 to 2018 (NCT02138721). Cytoreductive radical prostatectomy was offered to all fit patients with resectable tumours, resulting in 40 patients. Standard of care was administered to 40 patients who were ineligible or unwilling to undergo surgery. The primary endpoint was castration resistant cancer‐free survival at the time point of ≥50% events. The secondary endpoint was local event‐free survival. Kaplan–Meier and Cox regression analyses with propensity‐score analysis were applied.

Results

After a median (quartiles) follow‐up of 35 (24–47) months, 42 patients became castration‐resistant or died. The median castration resistant cancer‐free survival was 53 (95% confidence interval [CI] 14–92) vs 21 (95% CI 15–27) months for cytoreductive radical prostatectomy compared to standard of care (P = 0.017). The 3‐year estimates for local event‐free survival were 83% (95% CI 71–95) vs 59% (95% CI 51–67) for cytoreductive radical prostatectomy compared to standard of care (P = 0.012). However, treatment group showed no significance in the multivariable models for castration resistant cancer‐free survival (P = 0.5) or local event‐free survival (P = 0.3), adjusted for propensity‐score analysis. Complications were similar to the non‐metastatic setting. Patients undergoing surgery were younger, with lower baseline prostate‐specific antigen levels, alkaline phosphatase levels and metastatic burden.

Conclusion

The present LoMP study was unable to show a difference between the two inclusion groups regarding castration resistant cancer‐free survival for asymptomatic patients with newly diagnosed metastatic prostate cancer. These results validate previous evidence that, in well‐selected and informed patients, cytoreductive radical prostatectomy is feasible and safe, with corresponding continence rates compared to the non‐metastatic, high‐risk setting. Whether cytoreductive radical prostatectomy could be a valuable option to achieve good local palliation needs to be further researched. Overall, the role of cytoreductive radical prostatectomy needs to be further explored in randomized studies to correct for potential bias.
Pharmacological characterisation of mouse calcitonin and calcitonin receptor‐like receptors reveals differences compared with human receptors
Authors: Garelja Michael L. , Bower Rebekah L. , Brimble Margaret A. , Chand Shanan , Harris Paul W. R. , Jamaluddin Muhammad Aqfan , Petersen Jakeb , Siow Andrew , Walker Christopher S. , Hay Debbie L.
Published: July 2021

Background and Purpose

The calcitonin (CT) receptor family is complex, comprising two receptors (the CT receptor [CTR] and the CTR‐like receptor [CLR]), three accessory proteins (RAMPs) and multiple endogenous peptides. This family contains several important drug targets, including CGRP, which is targeted by migraine therapeutics. The pharmacology of this receptor family is poorly characterised in species other than rats and humans. To facilitate understanding of translational and preclinical data, we need to know the receptor pharmacology of this family in mice.

Experimental Approach

Plasmids encoding mouse CLR/CTR and RAMPs were transiently transfected into Cos‐7 cells. cAMP production was measured in response to agonists in the absence or presence of antagonists.

Key Results

We report the first synthesis and characterisation of mouse adrenomedullin, adrenomedullin 2 and βCGRP and of mouse CTR without or with mouse RAMPs. Receptors containing m‐CTR had subtly different pharmacology than human receptors; they were promiscuous in their pharmacology, both with and without RAMPs. Several peptides, including mouse αCGRP and mouse adrenomedullin 2, were potent agonists of the m‐CTR:m‐RAMP3 complex. Pharmacological profiles of receptors comprising m‐CLR:m‐RAMPs were generally similar to those of their human counterparts, albeit with reduced specificity.

Conclusion and Implications

Mouse receptor pharmacology differed from that in humans, with mouse receptors displaying reduced discrimination between ligands. This creates challenges for interpreting which receptor may underlie an effect in preclinical models and thus translation of findings from mice to humans. It also highlights the need for new ligands to differentiate between these complexes.

LINKED ARTICLES

This article is part of a themed issue on Advances in Migraine and Headache Therapy (BJP 75th Anniversary).. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.3/issuetoc
Children’s consent to child welfare services: Some explorative remarks
Authors: Pösö Tarja
Published: July 2021

In this article, children consenting to a care order proposal is explored as a form of meaningful participation as seen by care‐experienced young people. In contrast to health care and research ethics, almost no research exists on children's consent to child welfare measures. The findings suggest that instead of approaching children as individualistic rights‐holders, a more relational understanding about consenting is required, both conceptually and in practice, to acknowledge the social, emotional and power relations in which children's consent (or objection) becomes topical in child welfare. Without that recognition, consenting may be far from meaningful participation.
There are no differences in brachial artery endothelial shear stress and blood flow patterns between males and females during exercise
Authors: Gurovich Alvaro N. , Rodriguez Lisa , Morales‐Acuna Francisco
Published: July 2021

Premenopausal females have a lower cardiovascular risk than males. Sex differences on exercise‐induced endothelial shear stress (ESS) and blood flow patterns may explain part of this risk reduction. The purpose of this cross‐sectional study was to determine the differences in brachial artery exercise‐induced ESS and blood flow patterns between males and females. Thirty subjects (13 females) were recruited to perform a three‐workload steady‐state exercise test based on blood lactate levels (i.e. <2.0, 2.0–4.0, >4.0 mmol/l). ESS and blood flow patterns were estimated at rest and during each workload using Womersley's approximation and Reynolds number, respectively. Both males and females showed an exercise intensity‐dependent increase in antegrade and retrograde ESS. There was no significant sex effect or interaction for antegrade ESS (F(1, 30) = 0.715, p = 0.405 and F(1·672, 60) = 1.511, p = 0.232, respectively) or retrograde ESS (F(1, 30) = 0.794, p = 0.380 and F(1·810, 60) = 1.022, p = 0.361, respectively). Additionally, antegrade blood flow was turbulent during all bouts of exercise while retrograde blood flow became disturbed at moderate and high exercise intensities in both groups. There are no differences in exercise‐induced ESS and blood flow patterns between males and females when the exercise load is equivalent. This suggests that the vascular benefits of exercise training are similar in both sexes from a haemodynamic standpoint.
Trotz einer großen Auswahl wirksame Medikamente: Psoriatiker scheinen immer noch untertherapiert zu sein
Authors: Pilz Anna Caroline , Zink Alexander , Schielein Maximilian C. , Hell Katharina , Romer Katrin , Hillmann Elena , Bäumer Daniel , Reinhardt Maximilian , Wagner Nicola
Published: July 2021

Hintergrund und Ziele

Durch die Entwicklung neuer anti‐psoriatischer Medikamente und verbesserte Strukturen zu deren flächendeckender Einführung hat sich die medizinische Versorgung von Psoriasis‐Patienten deutlich verbessert. In dieser Studie haben wir die tatsächliche Inanspruchnahme des Gesundheitswesens untersucht und Gründe für die Unzufriedenheit der Betroffenen ermittelt.

Patienten und Methodik

Diese nicht‐interventionelle Querschnittsstudie wurde als anonyme Online‐Befragung von 12/2018 bis 01/2019 in Deutschland durchgeführt. Teilnehmer mit einer selbstberichteten, von einem Arzt gestellten Psoriasis‐Diagnose und Symptomen beantworteten Fragen zu ihrer Erkrankung, deren Einfluss auf das tägliche Leben und ihrer medizinischen Versorgung.

Ergebnisse

649 Teilnehmer mit einem mittleren Alter von 42,5 ± 13,7 Jahren und ausgewogener Geschlechterverteilung (männlich: 50,2 %) wurden ausgewertet. 54,1 % waren zum Zeitpunkt der Studie in ärztlicher Behandlung, 45,9 % nicht. Von den Teilnehmern mit medizinischer Versorgung waren 59,3 % nur mäßig oder weniger zufrieden mit ihrer Behandlung. Gründe für die Unzufriedenheit mit der Medikation waren unter anderem mangelnde Wirksamkeit und Nebenwirkungen. Von den nicht in ärztlicher Behandlung befindlichen Teilnehmern wurde “Zeitmangel des Arztes” als Hauptgrund für die Nichtinanspruchnahme ärztlicher Hilfe angegeben.

Schlussfolgerungen

Trotz der Verfügbarkeit effizienter Therapieoptionen in Deutschland sind viele Betroffene mit Psoriasis unzufrieden. Diese unterbehandelte Gruppe wurde als neue Zielgruppe identifiziert.
Fairness ideals in inventory allocation
Authors: Spiliotopoulou Eirini , Conte Anna
Published: July 2021

We study fairness ideals in distribution systems where inventory is allocated to multiple retailers and there is supply–demand mismatch. In particular, we focus on (a) what is considered fair inventory allocation by retailers (e.g., equal profit, same fill rate, equal share of supply–demand mismatch?) and (b) how the supply chain context affects fairness perceptions. We consider an integrated supply chain setting where total inventory is allocated at the retail level and retailers may face either shortage or surplus, and a disintegrated supply chain where retailers may face supply scarcity when total demand exceeds available inventory. Our experimental data suggest that subjects, taking on the role of retailers in the same supply chain, are often motivated by fairness considerations: they claim for themselves inventory that is not exactly equal to their needs in more than one‐third of the instances. Across settings, “fair” allocations depend on retail demands rather than on profit comparisons, even when these are facilitated by a decision support tool. However, in cases of surplus, the most prevalent fairness ideal is that of equal split of inventory–demand mismatch, while in cases of shortage, the most prevalent fairness ideal is that of equal fill rates. Follow‐up experiments suggest that retailers under both cases of shortage and surplus are more likely to evaluate an allocation as fair when it is based on realized demands, and this is independent of whether it was determined by a rule or a human decision maker.
Preoperative biliary drainage for pancreatic cancer
Authors: Nehme Fredy , Lee Jeffrey H.
Published: July 2021

Pancreatic adenocarcinoma is currently one of the leading causes of cancer‐related morbidity and mortality with dismal long term survival after diagnosis. Nearly 85% of pancreatic cancer patients present with advanced disease precluding curative surgical resection. In those who are candidates for surgery, preoperative biliary drainage (PBD) has been developed since the 1960s in order to improve surgical outcomes. While obstructive jaundice in resectable pancreatic cancer has been traditionally treated before surgical resection in all patients, data over the past decade demonstrated increased perioperative complications and morbidity with systematic PBD compared to direct surgery. With new evidence of potential adverse events, the role of routine PBD is being reassessed. Current indications for PBD include cholangitis, delayed surgery, and relief of jaundice in patients planned to receive neoadjuvant therapy (NAT). NAT is being increasingly utilized in borderline resectable as well as resectable pancreatic cancer and a higher proportion of patients with likely require PBD in the future. The evidence for endoscopic retrograde cholangiopancreatography as first line for PBD is robust with supporting data from endoscopic ultrasound assisted biliary drainage. Self‐expanding metal stent was shown to be cost‐effective in recent studies without increase in morbidity compared to plastic stents in this setting. In this review, we will summarize the current evidence for PBD in patients with pancreatic cancer.
The association of inadequate lip coverage and malocclusion with dental trauma in Brazilian children and adolescents – A systematic review and meta‐analysis
Authors: Vieira Walbert de Andrade , Pecorari Vanessa Gallego Arias , Gabriel Paulo Henrique , Vargas‐Neto Júlio , Santos Eduardo César Almada , Gomes Brenda Paula Figueiredo de Almeida , Ferraz Caio Cézar Randi , Almeida José Flávio Affonso de , Marciano Marina , de‐Jesus‐Soares Adriana
Published: July 2021

Background/Aim

Dental trauma (DT) occurs frequently in children and adolescents. Therefore, understanding the factors associated with its occurrence in these age groups is important to establish specific preventive measures. The aim of this study was to investigate the relationships of lip coverage, overjet, and open bite to dental trauma in Brazilian children and adolescents.

Material and methods

The review protocol was registered in the PROSPERO database (CRD42020156290) and the bibliographic search was performed in nine electronic databases until July 2020. The studies included were observational, performed in Brazil, with healthy children and adolescents (0–19 years old), and without the restriction of date or language. Two reviewers assessed the individual risk of bias of the eligible studies with a standardized checklist. The meta‐analyses were stratified by dentition stage and age range using fixed or random effects, odds ratio (OR) as the effect measure, and 95% confidence interval. The heterogeneity across studies was assessed with the I² test and the GRADE approach assessed the certainty of evidence.

Results

The search presented 2493 initial results, from which 55 met the eligibility criteria and were included. Most studies (67%) presented a low risk of bias and were published between 2000 and 2019. Children and adolescents with inadequate lip coverage are 1.86–2.36 times more likely to suffer from DT, while those with increased overjet are 1.94–3.11 times more likely. Children with primary dentitions and anterior open bites are 1.76 (95% CI: 1.20–2.59) times more likely to suffer from DT. The certainty of evidence varied from very low to moderate.

Conclusions

Inadequate lip coverage, increased overjet, and anterior open bite are associated with the occurrence of dental trauma in Brazilian children and adolescents.
Safety of the BNT162b2 COVID‐19 vaccine in multiple sclerosis (MS): Early experience from a tertiary MS center in Israel
Authors: Lotan Itay , Wilf‐Yarkoni Adi , Friedman Yitzhak , Stiebel‐Kalish Hadas , Steiner Israel , Hellmann Mark A.
Published: July 2021

Background and purpose

Although the COVID‐19 vaccines are currently recommended for people with multiple sclerosis (MS), the fact that they were not specifically tested in people with MS raises uncertainty regarding their safety in this population. The purpose of this study was to report real‐life safety data of the BNT162b2 COVID‐19 vaccine in a cohort of MS patients.

Methods

An anonymous survey was distributed to 425 MS patients. Participants were asked general demographic and disease‐related questions and specific questions regarding the safety profile of the COVID‐19 vaccine.

Results

Of the 425 MS patients, 262 completed the questionnaire. The median (range) participant age was 42 (22–79) years, 199 participants were women (75.9%), and 66 participants (25.2%) had associated comorbidities. A total of 198 participants (75.6%) were treated with disease‐modifying therapies. In all, 239 participants (91.2% of the responders) had received the BNT162b2 COVID‐19 vaccine. Of these, 182 (76.1%) were aged <55 years, and 57 (23.9%) were aged >55 years. Adverse events were reported by 136 participants (56.9%; 52.5% of those aged <55 years and 40.3% of those aged >55 years; p = 0.1517) and 36 participants (15.1%) reported new or worsening neurological symptoms following the vaccination, the most frequent being sensory disturbances (21 participants, 58.3%). Most symptoms occurred within the first 24 h after vaccination and resolved within 3 days. A total of 28 participants (77.8%) did not require any medication to treat their symptoms.

Conclusions

This survey indicates an overall favorable safety profile of the BNT162b2 vaccine in people with MS. These data should be confirmed in further prospective, large‐scale studies.
Differential behaviour and gene expression in 3D cultures of femoral‐ and calvarial‐derived human osteoblasts under a cyclic compressive mechanical load
Authors: Itskovich Yana , Meikle Murray C , Cannon Richard D , Farella Mauro , Coates Dawn E , Milne Trudy J
Published: July 2021

The aim of the study was to compare the response of calvarial and femoral osteoblasts cultured in a 3D hydrogel environment to cyclic compressive mechanical loading. Human foetal femoral and calvarial osteoblasts were encapsulated in a semi‐synthetic thiol‐modified hyaluronan gelatin polyethylene glycol diacrylate (PEGDA) cross‐linked HyStemC hydrogel. Constructs were subjected to a cyclic compressive strain of 33.4 kPa force every second for 5 s every hour for 6 h per day using FlexCell BioPress culture plates and compared to non‐compressed constructs. Cell viability, mineralisation, and morphological changes were observed over 21 days. BMP2, ALP, COL1A1, COL2A1, and OCN gene expression levels were quantified. Encapsulated osteoblast numbers increased and formed hydroxyapatite over a 21‐day period. Cell viability decreased under a cyclical strain when compared to cells under no strain. Femoral osteoblasts under strain expressed increased levels of BMP2 (53.9‐fold) and COL1A1 (5.1‐fold) mRNA compared to no strain constructs. Surprisingly, no BMP2 mRNA was detected in calvarial osteoblasts. Osteoblasts derived from endochondral (femoral) and intra‐membranous (calvarial) processes behaved differently in 3D‐constructs. We therefore recommend that site‐specific osteoblasts be used for future bone engineering and bone replacement materials and further research undertaken to elucidate how site‐specific osteoblasts respond to cyclic compressive loads.
Patient specific prediction of temporal lobe epilepsy surgical outcomes
Authors: Benjumeda Marco , Tan Yee‐leng , González Otárula Karina A. , Chandramohan Dharshan , Chang Edward F. , Hall Jeffery A. , Bielza Concha , Larrañaga Pedro , Kobayashi Eliane , Knowlton Robert C.
Published: July 2021

Objective

Drug‐resistant temporal lobe epilepsy (TLE) is the most common type of epilepsy for which patients undergo surgery. Despite the best clinical judgment and currently available prediction algorithms, surgical outcomes remain variable. We aimed to build and to evaluate the performance of multidimensional Bayesian network classifiers (MBCs), a type of probabilistic graphical model, at predicting probability of seizure freedom after TLE surgery.

Methods

Clinical, neurophysiological, and imaging variables were collected from 231 TLE patients who underwent surgery at the University of California, San Francisco (UCSF) or the Montreal Neurological Institute (MNI) over a 15‐year period. Postsurgical Engel outcomes at year 1 (Y1), Y2, and Y5 were analyzed as primary end points. We trained an MBC model on combined data sets from both institutions. Bootstrap bias corrected cross‐validation (BBC‐CV) was used to evaluate the performance of the models.

Results

The MBC was compared with logistic regression and Cox proportional hazards according to the area under the receiver‐operating characteristic curve (AUC). The MBC achieved an AUC of 0.67 at Y1, 0.72 at Y2, and 0.67 at Y5, which indicates modest performance yet superior to what has been reported in the state‐of‐the‐art studies to date.

Significance

The MBC can more precisely encode probabilistic relationships between predictors and class variables (Engel outcomes), achieving promising experimental results compared to other well‐known statistical methods. Multisite application of the MBC could further optimize its classification accuracy with prospective data sets. Online access to the MBC is provided, paving the way for its use as an adjunct clinical tool in aiding pre‐operative TLE surgical counseling.
Global assessment of marine and freshwater recreational fish reveals mismatch in climate change vulnerability and conservation effort
Authors: Nyboer Elizabeth A. , Lin Hsien‐Yung , Bennett Joseph R. , Gabriel Joseph , Twardek William , Chhor Auston D. , Daly Lindsay , Dolson Sarah , Guitard Eric , Holder Peter , Mozzon Christina M. , Trahan Alexandria , Zimmermann Dennis , Kesner‐Reyes Kathleen , Garilao Cristina , Kaschner Kristin , Cooke Steven J.
Published: July 2021

Recreational fisheries contribute substantially to the sociocultural and economic well‐being of coastal and riparian regions worldwide, but climate change threatens their sustainability. Fishery managers require information on how climate change will impact key recreational species; however, the absence of a global assessment hinders both directed and widespread conservation efforts. In this study, we present the first global climate change vulnerability assessment of recreationally targeted fish species from marine and freshwater environments (including diadromous fishes). We use climate change projections and data on species’ physiological and ecological traits to quantify and map global climate vulnerability and analyze these patterns alongside the indices of socioeconomic value and conservation effort to determine where efforts are sufficient and where they might fall short. We found that over 20% of recreationally targeted fishes are vulnerable to climate change under a high emission scenario. Overall, marine fishes had the highest number of vulnerable species, concentrated in regions with sensitive habitat types (e.g., coral reefs). However, freshwater fishes had higher proportions of species at risk from climate change, with concentrations in northern Europe, Australia, and southern Africa. Mismatches in conservation effort and vulnerability were found within all regions and life‐history groups. A key pattern was that current conservation effort focused primarily on marine fishes of high socioeconomic value rather than on the freshwater and diadromous fishes that were predicted to be proportionately more vulnerable. While several marine regions were notably lacking in protection (e.g., Caribbean Sea, Banda Sea), only 19% of vulnerable marine species were without conservation effort. By contrast, 72% of freshwater fishes and 33% of diadromous fishes had no measures in place, despite their high vulnerability and cultural value. The spatial and taxonomic analyses presented here provide guidance for the future conservation and management of recreational fisheries as climate change progresses.
Academic freedom in contemporary Britain: A cause for concern?
Authors: Karran Terence , Beiter Klaus D. , Mallinson Lucy
Published: July 2021

Using comparable legal information, and empirical data from over 2000 members of the UK's University and College Union and 2000 staff in universities of the European states, gathered by means of similar surveys, this paper is a comparative assessment of the de jure protection for, and the de facto levels of, academic freedom enjoyed by academic staff in the UK, when compared to their EU counterparts. The paper examines the legal and constitutional protection for academic freedom and the current levels of, and changes to, the two substantive elements (freedom to teach and freedom to research) and three supportive components (autonomy, governance and tenure) of academic freedom. The study reveals that UK academic staff believe that there is a low level of protection for academic freedom and that it has declined, both in general, and with respect to the two substantive elements and three supportive components of academic freedom. Similar trends are evident in the EU states, but statistical tests reveal that for every measure utilised, the decline in academic freedom is significantly greater in the UK than in the EU states.
Stranger danger? Cue‐based trust in online consumer product review videos
Authors: Pfeuffer Alexander , Phua Joe
Published: July 2021

Trust is a significant factor in electronic word‐of‐mouth (eWOM) effects. Consumers often need to form judgements about others using heuristic cues when they cannot rely on previous cumulative experiences with an online entity. Drawing on the theoretical construct of cue‐based trust and signalling theory, this study aimed to identify and examine the efficacy of content attributes serving as trust cues in online consumer product review videos. A multi‐method study conducted a series of focus groups and a survey study; focus groups identified 18 content attributes intentionally provided by a content creator in product review videos that serve as trust cues. In the focus groups and the survey, six of these content attributes emerged as heuristic cues that are particularly effective at eliciting consumer trust. Findings contribute to the understanding of cue‐based trust and signalling theory in the eWOM context and hold practical implications for various stakeholders.
Effect of heat moisture treatment on resistant starch content among carbohydrate sources: a meta‐analysis
Authors: Faridah Didah Nur , Damaiyanti Sanaz , Indrasti Dias , Jayanegara Anuraga , Afandi Frendy Ahmad
Published: July 2021

Resistant starch (RS) can be generated through heat moisture treatment (HMT). The HMT was conducted by modifying starch using different ratio of moisture content, high temperature and heating time. A number of studies showed that the effects of HMT on RS contents in cereals, pulses, tubers and fruits were inconsistent. This study aimed to analyse the impact of HMT on RS level in various carbohydrate sources through a meta‐analysis approach. Study selection was conducted with the PRISMA method. There were 21 relevant studies and 67 data used for meta‐analysis. The database was analysed by using Hedges’ d. The results showed that there was a significant impact of HMT on RS level of cereals, especially wheat. The highest increase in RS levels for various carbohydrate sources in starch was influenced by the interaction of treatment between water content at 15 ≤ x < 25%, heating time at 0.25 < x ≤ 6 h and temperature at 120 ≤ x ≤ 130 °C.
COVID‐19: Thrombosis, thromboinflammation, and anticoagulation considerations
Authors: Levy Jerrold H. , Iba Toshiaki , Olson Lyra B. , Corey Kristen M. , Ghadimi Kamrouz , Connors Jean M.
Published: July 2021

Vascular endothelial injury is a hallmark of acute infection at both the microvascular and macrovascular levels. The hallmark of SARS‐CoV‐2 infection is the current COVID‐19 clinical sequelae of the pathophysiologic responses of hypercoagulability and thromboinflammation associated with acute infection. The acute lung injury that initially occurs in COVID‐19 results from vascular and endothelial damage from viral injury and pathophysiologic responses that produce the COVID‐19–associated coagulopathy. Clinicians should continue to focus on the vascular endothelial injury that occurs and evaluate potential therapeutic interventions that may benefit those with new infections during the current pandemic as they may also be of benefit for future pathogens that generate similar thromboinflammatory responses. The current Accelerating COVID‐19 Therapeutic Interventions and Vaccines (ACTIV) studies are important projects that will further define our management strategies. At the time of writing this report, two mRNA vaccines are now being distributed and will hopefully have a major impact on slowing the global spread and subsequent thromboinflammatory injury we see clinically in critically ill patients.
Unsupervised flow cytometry analysis in hematological malignancies: A new paradigm
Authors: Béné Marie C. , Lacombe Francis , Porwit Anna
Published: July 2021

Ever since hematopoietic cells became “events” enumerated and characterized in suspension by cell counters or flow cytometers, researchers and engineers have strived to refine the acquisition and display of the electronic signals generated. A large array of solutions was then developed to identify at best the numerous cell subsets that can be delineated, notably among hematopoietic cells. As instruments became more and more stable and robust, the focus moved to analytic software. Almost concomitantly, the capacity increased to use large panels (both with mass and classical cytometry) and to apply artificial intelligence/machine learning for their analysis. The combination of these concepts raised new analytical possibilities, opening an unprecedented field of subtle exploration for many conditions, including hematopoiesis and hematological disorders. In this review, the general concepts and progress achieved in the development of new analytical approaches for exploring high‐dimensional data sets at the single‐cell level will be described as they appeared over the past few years. A larger and more practical part will detail the various steps that need to be mastered, both in data acquisition and in the preanalytical check of data files. Finally, a step‐by‐step explanation of the solution in development to combine the Bioconductor clustering algorithm FlowSOM and the popular and widely used software Kaluza® (Beckman Coulter) will be presented. The aim of this review was to point out that the day when these progresses will reach routine hematology laboratories does not seem so far away.
Minimizing cost associated with management of heparin‐induced thrombocytopenia: A cost analysis of various laboratory testing models
Authors: Northam Kalynn A. , Johnson Jasmine A. , Behrens Allison , Chen Sheh‐Li , Kasthuri Raj S. , Rollins‐Raval Marian
Published: July 2021

Introduction

Management of patients with suspected heparin‐induced thrombocytopenia (HIT) can lead to significant costs. Reported cost‐saving initiatives have focused on minimizing inappropriate testing in low‐risk patients and optimizing alternative anticoagulant selection. We sought to further investigate how utilizing various HIT laboratory testing models would impact total cost of testing and alternative anticoagulant use.

Methods

Utilizing a retrospective cohort of adult patients tested for HIT over three years within our institution, we evaluated how utilization of four distinct laboratory models impacted total number of HIT test combinations completed, time to HIT testing finalization, percentage of patients discharged from the hospital prior to HIT testing finalization, total alternative anticoagulant days, and total anticipated major bleed events. Additionally, we calculated cost of laboratory testing and alternative anticoagulant associated with each model.

Results

A total of 482 patients were included in our cohort. A laboratory testing model that utilized an in‐house platelet factor 4 (PF4)‐heparin enzyme‐linked immunosorbent assay (ELISA) completed three days weekly, and reflex serotonin release assay (SRA) with a five‐day turnaround resulted in the shortest mean time to HIT testing finalization, lowest percentage of patients discharged prior to HIT testing finalization, and lowest total alternative anticoagulant days.

Conclusions

Institutions should evaluate current HIT laboratory testing practices and assess for opportunities for optimization. Testing models utilizing a PF4‐heparin antibody ELISA with a reflex SRA for positive results may improve testing metrics and lead to lower utilization of alternative anticoagulants.
Linking grain boundary structure and composition to microstructure in commercial‐grade‐doped specialty Aluminas
Authors: Marvel Christopher J. , Frueh Tobias , Compson Charles , Harmer Martin P.
Published: July 2021

The design of commercial‐grade specialty alumina for improved behavior relies on better understanding the complex interplay between high concentrations of intentional dopants and unintentional impurities, which are unavoidably introduced during industrial‐scale processing. In particular, dopants and impurities govern grain boundary structure/composition, grain growth, and bulk material properties. While the effects of single dopants in ultra‐high‐purity ceramics are well understood, the same concepts have not been adequately extended to commercial materials containing numerous impurities, especially when utilizing the latest atomic‐resolution characterization techniques to evaluate grain boundary structure and composition. Therefore, this work investigated the effects of varying co‐doping levels of MgO, CaO, and SiO2 on grain boundary structure and composition in commercial‐grade alumina by applying aberration‐corrected scanning transmission electron microscopy. First, it was observed that grain growth behavior, specifically grain morphology, in doped specialty aluminas was anomalous to ultra‐high‐purity alumina; in the composition range that was investigated in this study, Ca‐doped specialty alumina exhibited equiaxed grains, whereas Si‐doped specialty alumina exhibited elongated grains. Afterward, it was determined that elemental ratios of bulk doping concentrations differed from grain boundary compositions. Grain boundary compositions, as well as grain boundary structure, were therefore determined to be the dominant metrics to predict grain growth behavior. Overall, co‐doping effects on grain boundary structure and composition are the key parameters to consider to control commercial‐grade ceramics and improve material reliability.
Virtual reality application influences cognitive load‐mediated creativity components and creative performance in engineering design
Authors: Chen Yi‐Ching , Chang Yu‐Shan , Chuang Meng‐Jung
Published: July 2021

Virtual reality (VR) can promote design performance, and may generate a high cognitive load and affect creative design thinking as well. In order to examine the effect of VR application on cognitive load and engineering design creativity, this study recruited 81 eighth‐grade students as participants and employed a non‐equivalent‐groups quasi‐experimental design to examine how VR application influences creativity components and creative performance. A creativity component scale (creative motivation, creative thinking, and professional cognition), a measurement of creative performance, and a cognitive load scale were used to collect data. The study also investigated the ability of VR application to predict creativity components and creative performance, using cognitive load as the mediator. The conclusions are as follows: (1) VR application had marked effects on professional cognition and creative motivation but no effect on creative thinking skills. (2) VR application had marked effects on the novelty and usefulness aspects of creative performance, particularly with respect to usefulness. (3) VR application had marked effects on extraneous and germane cognitive load, but no influence on intrinsic cognitive load, and (4) Both VR application and cognitive load were able to predict creativity components and creative performance. Their abilities to predict creative performance approached an acceptable level. Nevertheless, VR application had no effect on general creative thinking skills; therefore, other teaching strategies are needed to strengthen creative thinking.
Balancing between Artemia and microdiet usage for normal skeletal development in zebrafish (Danio rerio)
Authors: Printzi Alice , Kourkouta Chara , Fragkoulis Stefanos , Dimitriadi Anastasia , Geladakis George , Orfanakis Michail , Mazurais David , Zambonino‐Infante Jose‐Luis , Koumoundouros George
Published: July 2021

Targeting in zebrafish fast growth, high survival rates and improved reproductive performance has led over the last years in variable feeding regimes between different facilities. Despite its significance on fish function and welfare, normal skeletal development has rarely been evaluated in establishing the best feeding practices for zebrafish. The aim of this study was to establish a protocol for normal skeletal development, growth and survival of zebrafish larvae through live feed‐to‐microdiet transition at an appropriate rate. Four feeding regimes including feeding exclusively on Artemia nauplii (A) or dry microdiet (D), and feeding on both Artemia and microdiet at two different transition rates (slow (B) or fast (C)) were applied from 5 to 24 dpf (days post‐fertilization). Results demonstrated a significant effect of feeding regimes on the incidence of skeletal abnormalities (gill cover, fins and vertebral column, p < .05) in zebrafish larvae. The A and B experimental groups presented the highest (88 ± 3 and 84 ± 17%, respectively), but the C and D the lowest (18 ± 14 and 11 ± 2%, respectively), rates of normal fish (fish without any abnormality). Similarly, growth rate was comparatively elevated in A and B groups. No significant differences were observed in fish survival between A, B and C groups. However, D group presented a significantly lower survival rate. To our knowledge, this is the first study to show that the live feed‐to‐microdiet transition rate influences larval growth, survival and abnormality rates in a non‐homogenous pattern.
Flood frequency analysis of Manas River Basin in China under non‐stationary condition
Authors: He Chaofei , Chen Fulong , Wang Yixuan , Long Aihua , He Xinlin
Published: July 2021

Incorporating 50 years of flood data for the Manas River Kenswat Hydrological Station from 1957 to 2006, the Pettitt test and Mann–Kendall trend test are used to analyse non‐stationarity of the flood characteristic sequences. Moreover, the Pearson type‐III (P‐III) distribution, the mixed distribution (MD) and conditional probability distribution (CPD) models are employed to analyse frequency and to calculate the design flood process line. The results showed that the annual maximum peak discharge and the annual maximum flood volume are most likely to change in 1993. The MD model considering the non‐stationarity of the flood sequence is more accurate than the CPD model and the traditional P‐III distribution model. There are significant differences in the design flood process lines of the 1996 typical flood process obtained by the three methods using the same frequency scaling method. In addition, under different design standards, the design value of the MD model is 20–53% smaller than the design value approved in 2008 (approved by China Renewable Energy Engineering Institute) and 4–48% higher than the traditional P‐III distribution design value. The results can provide a new reference for the management of non‐stationary floods in Manas River.
Kikuchi pattern simulations of backscattered and transmitted electrons
Authors: Winkelmann Aimo , Nolze Gert , Cios Grzegorz , Tokarski Tomasz , Bała Piotr , Hourahine Ben , Trager‐Cowan Carol
Published: July 2021

We discuss a refined simulation approach which treats Kikuchi diffraction patterns in electron backscatter diffraction (EBSD) and transmission Kikuchi diffraction (TKD). The model considers the result of two combined mechanisms: (a) the dynamical diffraction of electrons emitted coherently from point sources in a crystal and (b) diffraction effects on incoherent diffuse intensity distributions. Using suitable parameter settings, the refined simulation model allows to reproduce various thickness‐ and energy‐dependent features which are observed in experimental Kikuchi diffraction patterns. Excess‐deficiency features are treated by the effect of gradients in the incoherent background intensity. Based on the analytical two‐beam approximation to dynamical electron diffraction, a phenomenological model of excess‐deficiency features is derived, which can be used for pattern matching applications. The model allows to approximate the effect of the incident beam geometry as a correction signal for template patterns which can be reprojected from pre‐calculated reference data. As an application, we find that the accuracy of fitted projection centre coordinates in EBSD and TKD can be affected by changes in the order of – if excess‐deficiency features are not considered in the theoretical model underlying a best‐fit pattern matching approach. Correspondingly, the absolute accuracy of simulation‐based EBSD strain determination can suffer from biases of a similar order of magnitude if excess‐deficiency effects are neglected in the simulation model.
Comparative anatomy and phylogenetic contribution of intracranial osseous canals and cavities in armadillos and glyptodonts (Xenarthra, Cingulata)
Authors: Le Verger Kévin , González Ruiz Laureano R. , Billet Guillaume
Published: July 2021

The evolutionary history of the Cingulata, as for many groups, remains a highly debated topic to this day, particularly for one of their most emblematic representatives: the glyptodonts. There is no consensus among morphological and molecular phylogenies regarding their position within Cingulata. As demonstrated by recent works, the study of the internal anatomy constitutes a promising path for enriching morphological matrices for the phylogenetic study of armadillos. However, internal cranial anatomy remains understudied in the Cingulata. Here we explored and compared the anatomy of intracranial osseous canals and cavities in a diverse sample of extant and extinct cingulates, including the earliest well‐preserved glyptodont crania. The virtual 3D reconstruction (using X‐ray microtomography) of selected canals, that is, the nasolacrimal canal, the palatine canal, the sphenopalatine canal, the canal for the frontal diploic vein, the transverse canal, the orbitotemporal canal, the canal for the capsuloparietal emissary vein and the posttemporal canal, and alveolar cavities related to cranial vascularization, innervation or tooth insertion allowed us to compare the locations, trajectories, and shape of these structures and to discuss their potential interest for cingulate systematics. We tentatively reconstructed evolutionary scenarios for eight selected traits related to these structures in which glyptodonts often showed a close resemblance to pampatheres, to the genus Proeutatus, and/or to chlamyphorines. This latter pattern was partly congruent with recent molecular hypotheses, but more research is needed on these resemblances and on the potential effects of development and allometry on the observed variations. Overall, these comparisons have enabled us to highlight new anatomical variation that may be of great interest to further explore the evolutionary history of cingulates and the origins of glyptodonts on a morphological basis.
Paleobiological reconstructions of articular function require all six degrees of freedom
Authors: Manafzadeh Armita R. , Gatesy Stephen M.
Published: July 2021

Paleobiologists typically exclude impossible joint poses from reconstructions of extinct animals by estimating the rotational range of motion (ROM) of fossil joints. However, this ubiquitous practice carries the assumption that osteological estimates of ROM consistently overestimate true joint mobility. Because studies founded on ROM‐based exclusion have contributed substantially to our understanding of functional and locomotor evolution, it is critical that this assumption be tested. Here, we evaluate whether ROM‐based exclusion is, as currently implemented, a reliable strategy. We measured the true mobilities of five intact cadaveric joints using marker‐based X‐ray Reconstruction of Moving Morphology and compared them to virtual osteological estimates of ROM made allowing (a) only all three rotational, (b) all three rotational and one translational, and (c) all three rotational and all three translational degrees of freedom. We found that allowing combinations of motions in all six degrees of freedom is necessary to ensure that true mobility is always successfully captured. In other words, failing to include joint translations in ROM analyses results in the erroneous exclusion of many joint poses that are possible in life. We therefore suggest that the functional and evolutionary conclusions of existing paleobiological reconstructions may be weakened or even overturned when all six degrees of freedom are considered. We offer an expanded methodological framework for virtual ROM estimation including joint translations and outline recommendations for future ROM‐based exclusion studies.
External surface anatomy of the postfolding human embryo: Computer‐aided, three‐dimensional reconstruction of printable digital specimens
Authors: Azkue Jon Jatsu
Published: July 2021

Opportunities for clinicians, researchers, and medical students to become acquainted with the three‐dimensional (3D) anatomy of the human embryo have historically been limited. This work was aimed at creating a collection of digital, printable 3D surface models demonstrating major morphogenetic changes in the embryo's external anatomy, including typical features used for external staging. Twelve models were digitally reconstructed based on optical projection tomography, high‐resolution episcopic microscopy and magnetic resonance imaging datasets of formalin‐fixed specimens of embryos of developmental stages 12 through 23, that is, stages following longitudinal and transverse embryo folding. The reconstructed replica reproduced the external anatomy of the actual specimens in great detail, and the progress of development over stages was recognizable in a variety of external anatomical features and bodily structures, including the general layout and curvature of the body, the pharyngeal arches and cervical sinus, the physiological gut herniation, and external genitalia. In addition, surface anatomy features commonly used for embryo staging, such as distinct steps in the morphogenesis of facial primordia and limb buds, were also apparent. These digital replica, which are all provided for 3D visualization and printing, can serve as a novel resource for teaching and learning embryology and may contribute to a better appreciation of the human embryonic development.
Beyond Ethnicity: Applying Helms’s White Racial Identity Development Model Among White Youth
Authors: Moffitt Ursula , Rogers Leoandra Onnie , Dastrup Kara R. H.
Published: July 2021

Research on racial identity among Youth of Color has expanded considerably in recent years, but a parallel examination of racial identity among white youth has not occurred, reiterating whiteness as normative. We applied Janet Helms’s White Racial Identity Development (WRID) model among white U.S. youth (8–14 years old) to address this research gap. WRID centers racism and white supremacy, offering a framework to analyze white racial identity in the context of systemic inequity. Using longitudinal, qualitative analysis, we found age‐related change over time, with some evidence of increasing resistance to racism. There was high participant variability, however, indicating that socio‐cognitive abilities alone cannot predict anti‐racist white identity development. We discuss implications for racial identity research and social justice‐orientated developmental science.