bluuebunny/crossref_metadata_2025 huggingface dataset:
Management effects on soil nematode abundance differ among functional groups and land‐use types at a global scale
Authors: Li Xianping , Liu Ting , Li Huixin , Geisen Stefan , Hu Feng , Liu Manqiang
Published: May 2022

Anthropogenic land use is threatening global biodiversity. As one of the most abundant animals on Earth, nematodes occupy several key positions in belowground food webs and contribute to many ecosystem functions and services. However, the effects of land use on nematode abundance and its determinants remain poorly understood at a global scale.

To characterize nematodes' responses to land use across trophic groups, we used a dataset of 6,825 soil samples globally to assess how nematode abundance varies among regional land‐use types (i.e. primary vegetation, secondary vegetation, pasture, cropland and urban) and local land‐use intensities (i.e. human‐managed or not). We also quantified the interactive effects of land use and environmental predictors (i.e. mean annual temperature, annual precipitation, soil organic carbon, soil pH, global vegetation biomass and global vegetation productivity) on nematode abundance.

We found that total nematode abundance and the abundance of bacterivores, fungivores, herbivores, omnivores and predators generally increased or were not affected under management across land‐use types. Specifically, the most numerically abundant bacterivores were higher in managed than in unmanaged secondary vegetation habitats and urban areas, and herbivores were more abundant in managed than in unmanaged primary and secondary vegetation habitats. Furthermore, the numbers of significant environmental predictors of nematode abundance were reduced and the magnitude and the direction of the predictors were changed under management. We also found that nematode abundance was more variable and less determined by environmental factors in urban than in other land‐use types.

These findings challenge the view that human land use decreases animal abundance across trophic groups, but highlight that land use is altering the trophic composition of soil nematodes and its relationships with the environment at the global scale.
Evaluating staging habitat quality to advance the conservation of a declining migratory shorebird, Red Knot Calidris canutus
Authors: Mu Tong , Cai Shangxiao , Peng He‐Bo , Hassell Chris J. , Boyle Adrian , Zhang Zhengwang , Piersma Theunis , Wilcove David S.
Published: May 2022

Identifying where and when population ‘bottlenecks’ occur is critical to the conservation of migratory species, many of which are declining precipitously worldwide. Especially challenging is the evaluation of changes to staging sites. These sites are indispensable links in the migratory cycle but are typically used only briefly.

We devised a field‐based approach to assess the quality and carrying capacity of a critical staging site in Nanpu, China, for the declining, migratory Red Knot (Calidris canutus rogersi & C. c. piersmai) during northward migration. The Nanpu tidal flat supports 50,000–100,000 Red Knots annually, and while there, the knots feed almost exclusively on the bivalve Potamocorbula laevis. We simultaneously monitored changes in the abundance of Red Knots and bivalves across this entire staging site in spring 2018.

After taking into account potential competition with other shorebird species, we estimated that the Nanpu tidal flat was capable of supporting approximately 1.46–1.70 times the observed level of Red Knot usage of this site, and therefore is operating below, but close to, carrying capacity with respect to food resources for Red Knots. This result suggests that any further habitat loss or degradation at this site could harm the Red Knot population along the entire East Asian‐Australasian Flyway.

Synthesis and applications. Quantitative monitoring and evaluation of habitat quality of staging sites are essential to successfully conserve declining migratory species. In particular, researchers and conservation practitioners should incorporate both population size and staging duration to more accurately assess the importance of different sites and to quantify how changes in staging habitat quality may translate into changes in the population sizes of migratory species at both local and global scales.
Forearmed is forewarned: A prospective intervention observational time‐series study of patient empowerment for ultrasound‐guided peripheral intravenous access
Authors: Libbis Eng , Sweeny Amy L , Holmes Travis , Aggarwal Nisha , Snelling Peter J , Slaughter Eugene , Poncia Hugo , Watkins Stuart C
Published: May 2022

Objective

Ultrasound (US) is a valuable adjunct to improve the success rates of difficult peripheral intravenous cannula (PIVC) insertions but is usually clinician initiated. The present study assessed for any change in clinician practice resulting from interventions aimed at empowering patients to advocate for early use of US if they self‐identified as having difficult PIVC access.

Methods

This was a prospective observational time‐series study using a rapid quality improvement (RQI) framework. Three ED waiting room intervention strategies (printed media, video and wristband) were tested over three 2‐week periods at a large teaching hospital. The impact of each intervention was assessed at eight time points during each intervention and compared to a pre‐intervention baseline period using trend and time‐series analysis.

Results

A total of 1611 PIVC insertions were surveyed over 42 time points. The proportion of US‐guided PIVC insertions was highest during Intervention 3 (wristbands; 5.5%) but all proportions remained below baseline (6.5%). Trend analysis identified an increasing frequency of US use during Intervention 1 (printed media, P = 0.01). However, no statistically significant trends were observed within the periods.

Conclusions

This is the first prospective study to assess the effect of various interventions to empower patients to self‐identify as having difficult PIVC access and advocate for the use of US‐guidance. The present study was indeterminate: no intervention tested in the present study noticeably influenced clinical practice, potentially attributable to the study design and confounding factors. This innovative study serves as a pilot for future research into patient empowerment, which is currently lacking in the literature.
Recovering the genomes hidden in museum wet collections
Authors: Ruiz‐Gartzia Irune , Lizano Esther , Marques‐Bonet Tomas , Kelley Joanna L.
Published: May 2022

Natural history museums hold vast collections of biomaterials. The collections in museums, often painstakingly sampled, are largely unexplored treasures that may help us better understand biodiversity on the planet. Museum collections can provide a unique window into the past of species long gone or currently declining due to human activity. From a molecular perspective, however, many museum samples are stored under conditions that hasten the damage of DNA, RNA and proteins. For example, samples in wet collections are those stored in liquid preservatives, typically ethanol. These ethanol‐preserved tissues are often, although not always, formalin‐fixed prior to storage, which may damage DNA. In this and recent issues of Molecular Ecology Resources, Straube et al (2021), O'Connell et al (2021) and Hahn et al (2022) explore different types of specimens from museum wet collections as new sources of DNA for scientific studies. All three articles found that for wet museum collections, overall specimen condition mattered most for recovering high‐quality genomic DNA.
Determinants and Consequences of the Severity of Executive Compensation Clawbacks*
Authors: Asante‐Appiah Bright , Sharma Divesh S.
Published: May 2022

We examine the determinants and consequences of the severity of executive compensation clawbacks. As one of the most substantial, prolonged, and controversial proposals to reform executive compensation, clawback rules recently regained the SEC's focus. We construct an intuitive clawback severity score and find that clawbacks are considerably heterogeneous and not homogenous as assumed in the literature. Our determinants analyses suggest that clawback severity is increasing in firms with greater board effectiveness and with higher cash and stock awards in director compensation. In contrast, higher director stock option compensation and more powerful CEOs attenuate the severity of clawbacks. The consequences analyses indicate that while severe clawbacks deter financial restatements, management circumvents severe clawbacks by reducing R&D expenses to avoid earnings decreases. One consistent finding throughout our analyses is that the associations are entirely driven by more severe clawbacks. However, we observe that the financial reporting benefits of severe clawbacks can be diminished by the dynamics in the boardroom. Our study extends extant clawback literature, makes a timely contribution to the SEC's decision to reinitiate discussion on clawbacks, and informs various stakeholders interested in the efficacy of clawbacks. Finally, our clawback score can be used to evaluate clawback policies.
Taxonomic, functional, and phylogenetic diversity of lizard assemblages across habitats and seasons in a Brazilian Cerrado area
Authors: Barros Rafael Assis , Dorado‐Rodrigues Tainá Figueras , Strüssmann Christine
Published: May 2022

One of the core issues in community ecology is the understanding of mechanisms that determine community structure. In this study, we examine how two structurally distinct habitats (campo sujo – a grassy savanna habitat with low shrubby cover – and seasonal semi‐deciduous forest) and distinct hydrological seasons (dry and rainy) influence the taxonomic, functional and phylogenetic diversity of lizard assemblages in a savanna area in the Brazilian Cerrado. We used pitfall traps to sample lizards from May 2000 to February 2002. To quantify spatio‐temporal changes in the lizard assemblages, we used parameters of taxonomic (species richness – SR), functional (functional diversity – SES.FD, functional redundancy – FR and functional dispersion – FDis), and phylogenetic diversity (phylogenetic species richness – PSR and phylogenetic species variability – PSV). We also estimate functional and phylogenetic structure of the assemblages in each habitat during dry and rainy seasons. We recorded 182 lizards distributed among 14 species. Species composition differed among habitat types, but did not differ seasonally within habitats. SES.FD, FDis, and FR also differed among habitat types but not among seasons, with SES.FD and FDis being greater in seasonal semi‐deciduous forest, while FR was greater in campo sujo. SR, PSR, and PSV were not influenced by the factors analysed. The lizard assemblage of campo sujo was functionally clustered in the dry season and phylogenetically clustered in the rainy season. These results demonstrate that differences among habitat types and seasons are important in shaping the taxonomic, functional, phylogenetic diversity and structure of lizard assemblages in the savanna area studied. Our study also demonstrates the importance of using different measures of diversity to obtain a better understanding on the mechanisms that influence the lizard assemblages in a highly seasonal environment.
Airway remodelling rather than cellular infiltration characterizes both type2 cytokine biomarker‐high and ‐low severe asthma
Authors: Khalfaoui Latifa , Symon Fiona A. , Couillard Simon , Hargadon Beverley , Chaudhuri Rekha , Bicknell Steve , Mansur Adel H. , Shrimanker Rahul , Hinks Timothy S. C. , Pavord Ian D. , Fowler Stephen J. , Brown Vanessa , McGarvey Lorcan P. , Heaney Liam G. , Austin Cary D. , Howarth Peter H. , Arron Joseph R. , Choy David F. , Bradding Peter
Published: May 2022

Background

The most recognizable phenotype of severe asthma comprises people who are blood eosinophil and FeNO‐high, driven by type 2 (T2) cytokine biology, which responds to targeted biological therapies. However, in many people with severe asthma, these T2 biomarkers are suppressed but poorly controlled asthma persists. The mechanisms driving asthma in the absence of T2 biology are poorly understood.

Objectives

To explore airway pathology in T2 biomarker‐high and ‐low severe asthma.

Methods

T2 biomarker‐high severe asthma (T2‐high, n = 17) was compared with biomarker‐intermediate (T2‐intermediate, n = 21) and biomarker‐low (T2‐low, n = 20) severe asthma and healthy controls (n = 28). Bronchoscopy samples were processed for immunohistochemistry, and sputum for cytokines, PGD2 and LTE4 measurements.

Results

Tissue eosinophil, neutrophil and mast cell counts were similar across severe asthma phenotypes and not increased when compared to healthy controls. In contrast, the remodelling features of airway smooth muscle mass and MUC5AC expression were increased in all asthma groups compared with health, but similar across asthma subgroups. Submucosal glands were increased in T2‐intermediate and T2‐low asthma. In spite of similar tissue cellular inflammation, sputum IL‐4, IL‐5 and CCL26 were increased in T2‐high versus T2‐low asthma, and several further T2‐associated cytokines, PGD2 and LTE4, were increased in T2‐high and T2‐intermediate asthma compared with healthy controls.

Conclusions

Eosinophilic tissue inflammation within proximal airways is suppressed in T2 biomarker‐high and T2‐low severe asthma, but inflammatory and structural cell activation is present, with sputum T2‐associated cytokines highest in T2 biomarker‐high patients. Airway remodelling persists and may be important for residual disease expression beyond eosinophilic exacerbations.

Registered at ClincialTrials.gov: NCT02883530.
Online training module for micro suturing incorporating motor imagery and mental practice: a design and development research study
Authors: Rajaratnam Vaikunthan , Ng Hannah Jia Hui , Rahman Norana Abdul , Dong Chaoyan
Published: May 2022

Introduction

There have been reduced opportunities for surgical skill acquisition due to the COVID‐19 pandemic and the regulated training hours. Despite these challenges, self‐regulated learning allows trainees to learn continuously, and one form of this is through mental practice and motor imagery. The study aimed to design and develop an online basic micro suturing training module for skill acquisition for self‐regulated learning using a low‐fidelity rubber glove model.

Methods

This study utilized a design and developmental research framework and Mayer's multimedia theory guidelines. The primary author created an online instructional module on micro suturing based on the ADDIE instructional design model. This module was then evaluated in a pilot study comparing the new training model to traditional methods of learning using an experimental design.

Results

This study describes the use of Design and Development Research to create a new model for surgical skill training and a tool for producing instructional materials and learning products for online learning. The product was evaluated using an experimental design and showed a significant effect on the quality of motor skill outcome and the richness of motor imagery using the resource developed in the research.

Conclusion

This study describes the methodological approach of a design and developmental framework to create an online training module for micro suturing which has significant utility in hand surgery.
Primary hepatic epithelioid angiomyolipoma: a small case series
Authors: Zhu Jisheng , Wang Guiyan , Sun Gen , Xie Bin , Xiao Weidong , Li Yong
Published: May 2022

Background

Hepatic epithelioid angiomyolipomas (HEAMLs) are rare and usually arise in case reports, and thus, we aimed to study the clinicopathological features, treatment and prognosis of these lesions.

Methods

We identified patients from institutional database with HEAMLs and retrospectively collected clinical data.

Results

Of 12 patients, 10 were females, and the median age was 49 years. A liver mass was found on chance upon routine health screening in nine patients. Imaging features included clear border (9/12), internal heterogeneity (8/12), arterial enhancement (12/12), fat (5/12), intra‐tumour vessel (3/12), draining hepatic vein (2/12) and pseudocapsule (1/12). The preoperative diagnoses contained HEAML (n = 5), hepatocellular carcinoma (n = 6), and hepatic cystadenocarcinoma (n = 1). All cases had received surgery and obtained a negative margin. All specimens showed positive findings for HMB‐45 and Melan A. No tumour recurrence or mortality was described with a mean follow‐up time of 23.5 months.

Conclusions

HEAML is a low potential malignancy tumour that frequently appears in middle‐aged females. It has nonspecific symptoms and may present special imaging features including intra‐tumour vessel, early draining hepatic vein and lack of a pseudo capsule. The lesion is confirmed by pathological and immunohistochemical findings. Surgery and subsequent long‐term follow‐up are the most appropriate management approaches.
A snapshot of intraoperative conditions to predict prolonged postoperative ileus after colorectal surgery
Authors: de Gaay Fortman Duveke P. E. , Kroon Hidde M. , Bedrikovetski Sergei , Fitzsimmons Tracy R. , Dudi‐Venkata Nagendra N. , Sammour Tarik
Published: May 2022

Background

The cause of prolonged postoperative ileus (PPOI) is multifactorial. The influence of preoperative factors on PPOI has been well documented, but little is known about the impact of intraoperative conditions. The aim of this study was to investigate the influence of intraoperative factors on PPOI in patients undergoing colorectal surgery.

Methods

The LekCheck study database of the Colorectal Unit at the Royal Adelaide Hospital was analysed. Per patient, over 60 data points were prospectively collected between March 2018 and July 2020. Intraoperative data were collected in theatre during a one‐off snapshot measure. Univariate and multivariable logistic regression analyses were performed.

Results

Data of 336 patients were included. The median age was 66 years and 58.3% were male. Ninety‐three patients (27.7%) developed PPOI. Univariate analysis identified the following intraoperative variables as risk‐factors of PPOI: greater volumes of intraoperative IV fluid administration (464 versus 415 mL/h for those without PPOI; p = 0.04), side‐to‐side anastomosis orientation (53.8 versus 41.2%; p = 0.04) and increased perioperative opioid use (6.73 versus 4.11 mg/kg morphine equivalents for patients with and without PPOI, respectively; p = 0.02). Upon multivariable analysis, increased perioperative opioid use remained significant (p = 0.05), as well as the preoperative factors anticoagulation use (p = 0.04) and higher levels of serum total protein (p = 0.02).

Conclusion

This study suggests that intraoperative factors may also contribute to the development of PPOI, but this could not be confirmed in the multivariate analysis. Further studies including larger patient numbers will be required to determine the impact of intraoperative conditions on the development of PPOI.
Feline immunodeficiency virus (FIV) infection in domestic pet cats in Australia and New Zealand: Guidelines for diagnosis, prevention and management
Authors: Westman ME , Coggins SJ , van Dorsselaer M , Norris JM , Squires RA , Thompson M , Malik R
Published: May 2022

Despite the passage of over 30 years since its discovery, the importance of feline immunodeficiency virus (FIV) on the health and longevity of infected domestic cats is hotly debated amongst feline experts. Notwithstanding the absence of good quality information, Australian and New Zealand (NZ) veterinarians should aim to minimise the exposure of cats to FIV. The most reliable way to achieve this goal is to recommend that all pet cats are kept exclusively indoors, or with secure outdoor access (e.g., cat enclosures, secure gardens), with FIV testing of any in‐contact cats. All animal holding facilities should aim to individually house adult cats to limit the spread of FIV infection in groups of animals that are stressed and do not have established social hierarchies. Point‐of‐care (PoC) FIV antibody tests are available in Australia and NZ that can distinguish FIV‐infected and uninfected FIV‐vaccinated cats (Witness™ and Anigen Rapid™). Although testing of whole blood, serum or plasma remains the gold standard for FIV diagnosis, PoC testing using saliva may offer a welfare‐friendly alternative in the future. PCR testing to detect FIV infection is not recommended as a screening procedure since a negative PCR result does not rule out FIV infection and is only recommended in specific scenarios. Australia and NZ are two of three countries where a dual subtype FIV vaccine (Fel‐O‐Vax® FIV) is available and offers a further avenue for disease prevention. Since FIV vaccination only has a reported field effectiveness of 56% in Australia, and possibly lower in NZ, FIV‐vaccinated cats should undergo annual FIV testing prior to annual FIV re‐vaccination using a suitable PoC kit to check infection has not occurred in the preceding year. With FIV‐infected cats, clinicians should strive to be even more thorough than usual at detecting early signs of disease. The most effective way to enhance the quality of life and life expectancy of FIV‐infected cats is to optimise basic husbandry and to treat any concurrent conditions early in the disease course. Currently, no available drugs are registered for the treatment of FIV infection. Critically, the euthanasia of healthy FIV‐infected cats, and sick FIV‐infected cats without appropriate clinical investigations, should not occur.
Central anticholinergic syndrome secondary to atropine eye drops: A case study
Authors: Soletchnik Mickael , Rousseau Geoffroy , Gonzalez Lola , Laribi Saïd
Published: May 2022

Atropine eye drops are frequently used in the treatment of keratitis and during ophthalmic surgery. We described a rare complication of central anticholinergic syndrome secondary to atropine eye drops.
The structure of executive functioning in 11 to 14 year olds with and without special educational needs
Authors: Messer David , Kearvell‐White Jennifer , Danielsson Henrik , Faulkner Dorothy , Henry Lucy , Ibbotson Paul
Published: May 2022

The structure and development of executive functioning (EF) have been intensively studied in typically developing populations, with little attention given to those with Special Educational Needs (SEN). This study addresses this by comparing the EF structure of 132 adolescents (11–14 years‐old) with SEN and 138 adolescents not requiring additional support (Non‐SEN peers). Participants completed verbal and non‐verbal assessments of key components of EF: inhibition, working memory and switching. Confirmatory Factor Analysis on each group tested one‐, two‐ and three‐factor models of EF. In both groups, there was statistical support for the fit of one‐ and two‐factor models with no model being clearly better than the others; there was little support for three‐factor models. Parsimony suggests that the one‐factor model best represents the structure of EF. In light of our results, the implications for the nature of EF in early adolescence in both SEN and Non‐SEN groups are discussed.
Anti‐severe acute respiratory syndrome coronavirus‐2 adenoviral‐vector vaccines trigger subclinical antiplatelet autoimmunity and increase of soluble platelet activation markers
Authors: Petito Eleonora , Colonna Elisabetta , Falcinelli Emanuela , Mezzasoma Anna Maria , Cesari Enrica , Giglio Elisa , Fiordi Tiziana , Almerigogna Fabio , Villa Alfredo , Gresele Paolo
Published: May 2022

To slow down the coronavirus disease 2019 (COVID‐19) pandemic an unequalled vaccination campaign was initiated. Despite proven efficacy and safety, a rare but potentially fatal complication of adenoviral‐vector vaccines, called vaccine‐induced immune thrombotic thrombocytopenia (VITT), has emerged the pathogenesis of which seems to be related to the development of platelet‐activating anti‐platelet factor 4 (PF4) antibodies. While a few studies have evaluated the incidence of anti‐PF4 positivity in anti‐severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccine recipients, to date no studies have assessed whether an antiplatelet immunological response develops and if this associates with platelet and blood clotting activation. We carried out a prospective study in healthy subjects who received the first dose of ChAdOx1 or Ad26.COV2.S or BNT162b2 vaccines to evaluate platelet‐specific and non‐specific immune response and in vivo platelet activation and blood clotting activation. Individuals receiving ChAdOx1 and, less so, Ad26.COV2.S developed with high frequency auto‐ or alloantiplatelet antibodies, increased circulating platelet‐derived microvesicles and soluble P‐selectin associated with mild blood clotting activation. Our study shows that an immunological reaction involving platelets is not uncommon in individuals receiving anti‐SARS‐CoV‐2 vaccination, especially after ChAdOx1 and Ad26.COV2.S, and that it associates with in vivo platelet and blood clotting activation.
Minimal residual disease and imaging‐guided consolidation strategies in newly diagnosed and relapsed refractory multiple myeloma
Authors: Böckle David , Tabares Paula , Zhou Xiang , Schimanski Sven , Steinhardt Maximilian J. , Bittrich Max , Seebacher Elena , Ulbrich Maria , Wilnit Amy , Metz Corona , Heidemeier Anke , Bley Thorsten , Werner Rudolf , Buck Andreas , Einsele Hermann , Kortüm K. Martin , Beilhack Andreas , Rasche Leo
Published: May 2022

Measurement of minimal residual disease (MRD) by next‐generation flow cytometry (NGF) is an important tool to define deep responses in multiple myeloma (MM). However, little is known about the value of combining NGF with functional imaging and its role for MRD‐based consolidation strategies in clinical routine. In the present study, we report our experience investigating these issues with 102 patients with newly diagnosed (n = 57) and relapsed/refractory MM (n = 45). Imaging was performed using either positron emission tomography or diffusion‐weighted magnetic resonance imaging. In all, 45% of patients achieved MRD‐negativity on both NGF and imaging (double‐negativity), and 8% and 40% of patients were negative on either NGF or imaging respectively. Thus, in a minority of patients imaging was the only technique to detect residual disease. Imaging‐positivity despite negativity on NGF was more common in heavily pretreated disease (four or more previous lines) compared to newly diagnosed MM (p < 0.01). Among the 29 patients undergoing MRD‐triggered consolidation, 51% responded with MRD conversion and 21% with improved serological response. MRD‐triggered consolidation led to superior progression‐free survival (PFS) when compared to standard treatment (p = 0.04). In conclusion, we show that combining NGF with imaging is helpful particularly in patients with heavily pretreated MM, and that MRD‐based consolidation could lead to improved PFS.
To control or not to control: How to organize employee‐driven innovation
Authors: Flocco Nicole , Canterino Filomena , Cagliano Raffaella
Published: May 2022

Nowadays organizations are increasingly understanding the relevance of employees for innovation. Innovative initiatives that involve larger groups of employees, despite their role and hierarchical position, are more and more diffused within companies. However, the literature on this topic is still at its infancy, especially considering those initiatives that are structured and organized by management. Using multiple case studies, performing 34 semistructured interviews in five different companies, we investigate how managers navigate alternative design choices when they organize employee‐driven innovation (EDI). Our findings suggest companies adopt different structures to organize EDI (i.e., open, closed, and hybrid), depending on the desired goals they want to achieve (i.e., creating a community or producing innovation). In this paper, we provide a clustering of different EDI practices (i.e., community‐nurturing practices, solution‐based practices, and integrative practices), outlining how managers can configure different design choices (e.g., topic definition, team creation, ideas transfer, ideas filtering and evaluation, and task division and allocation) to drive employees' involvement and to produce innovation.
Development of a potent small‐molecule degrader against oncogenic BRAFV600E protein that evades paradoxical MAPK activation
Authors: Ohoka Nobumichi , Suzuki Masanori , Uchida Takuya , Tsukumo Yoshinori , Yoshida Masayuki , Inoue Takao , Ohki Hitoshi , Naito Mikihiko
Published: May 2022

BRAF mutations are frequently observed in melanoma and hairy‐cell leukemia. Currently approved rapidly accelerated fibrosarcoma (RAF) kinase inhibitors targeting oncogenic BRAF V600 mutations have shown remarkable efficacy in the clinic, but their therapeutic benefits are occasionally hampered by acquired resistance due to RAF dimerization–dependent reactivation of the downstream MAPK pathway, which is known as paradoxical activation. There is also a concern that paradoxical activation of the MAPK pathway may trigger secondary cancer progression. In this study, we developed chimeric compounds, proteolysis targeting chimeras (PROTACs), that target BRAFV600E protein for degradation. CRBN(BRAF)‐24, the most effective chimera, potently degraded BRAFV600E in a ubiquitin‐proteasome system (UPS)‐dependent manner and inhibited the proliferation of BRAFV600E‐driven cancer cells. In BRAF wild‐type cells, CRBN(BRAF)‐24 induced neither BRAFWT degradation nor paradoxical activation of the MAPK pathway. Biochemical analysis revealed that CRBN(BRAF)‐24 showed more potent and sustained suppression of MAPK signaling than a BRAFV600E inhibitor, PLX‐8394, in BRAFV600E‐driven cancer cells. Targeted degradation of BRAFV600E by CRBN(BRAF)‐24 could be a promising strategy to evade paradoxical activation of the RAF‐MAPK pathway.
Open‐sleeve templates for computer‐assisted implant surgery at healed or extraction sockets: An in vitro comparison to closed‐sleeve guided system and free‐hand approach
Authors: Li Junying , Meneghetti Priscila Ceolin , Galli Matthew , Mendonca Gustavo , Chen Zhaozhao , Wang Hom‐Lay
Published: May 2022

Objective

A buccal opening guide provides better view and better irrigation. The aim of this study was to investigate the accuracy of this open‐sleeve system.

Material and Methods

Thirty duplicated maxillary models, each with six extraction sockets and four healed sites, were used. Based on the same digital plan, three modalities, sCAIS with open‐sleeves, closed‐sleeves, and free‐hand approach, were used to place implants. The global, horizontal, depth, and angular deviations between the virtual and actual implant positions were measured.

Results

Both sCAIS groups exhibited better accuracy than the free‐hand group in two clinical scenarios. At healed sites, the closed‐sleeve group showed a significantly fewer error than the open‐sleeve group in global apical (0.68 ± 0.33 vs. 0.96 ± 0.49 mm), horizontal coronal (0.28 ± 0.15 vs. 0.44 ± 0.25 mm), horizontal apical (0.64 ± 0.32 vs. 0.94 ± 0.48 mm), and angular deviations (1.83 ± 0.95 vs. 2.86 ± 1.46°). For extraction sockets, the open‐sleeve group exhibited fewer deviations than the closed‐sleeve group in terms of global (coronal: 0.77 ± 0.29 vs. 0.91 ± 0.22 mm; apical: 1.08 ± 0.49 vs. 1.37 ± 0.52 mm) and horizontal (coronal: 0.60 ± 0.24 vs. 0.86 ± 0.20 mm; apical: 0.95 ± 0.50 vs. 1.32 ± 0.51 mm) deviations. However, the closed‐sleeve group was more accurate in the depth control (0.26 ± 0.20 vs. 0.40 ± 0.31 mm).

Conclusion

In this in vitro investigation, open‐sleeve sCAIS proved better accuracy than free‐hand surgery for both delayed and immediate implant placement. Compared with a closed‐sleeve sCAIS system, open sleeve have the potential of providing better outcomes in extraction sockets but not in healed sites.
Community, Time, and (Con)text: A Dynamical Systems Analysis of Online Communication and Community Health among Open‐Source Software Communities
Authors: Paxton Alexandra , Varoquaux Nelle , Holdgraf Chris , Geiger R. Stuart
Published: May 2022

Free and open‐source software projects have become essential digital infrastructure over the past decade. These projects are largely created and maintained by unpaid volunteers, presenting a potential vulnerability if the projects cannot recruit and retain new volunteers. At the same time, their development on open collaborative development platforms provides a nearly complete record of the community's interactions; this affords the opportunity to study naturally occurring language dynamics at scale and in a context with massive real‐world impact. The present work takes a dynamical systems view of language to understand the ways in which communicative context and community membership shape the emergence and impact of language use—specifically, sentiment and expressions of gratitude. We then present evidence that these language dynamics shape newcomers' likelihood of returning, although the specific impacts of different community responses are crucially modulated by the context of the newcomer's first contact with the community.
Indefinite Pronouns Optimize the Simplicity/Informativeness Trade‐Off
Authors: Denić Milica , Steinert‐Threlkeld Shane , Szymanik Jakub
Published: May 2022

The vocabulary of human languages has been argued to support efficient communication by optimizing the trade‐off between simplicity and informativeness. The argument has been originally based on cross‐linguistic analyses of vocabulary in semantic domains of content words, such as kinship, color, and number terms. The present work applies this analysis to a category of function words: indefinite pronouns (e.g., someone, anyone, no one). We build on previous work to establish the meaning space and featural make‐up for indefinite pronouns, and show that indefinite pronoun systems across languages optimize the simplicity/informativeness trade‐off. This demonstrates that pressures for efficient communication shape both content and function word categories. In doing so, our work aligns with several concurrent studies exploring the simplicity/informativeness trade‐off in functional vocabulary. Importantly, we further argue that the trade‐off may explain some of the universal properties of indefinite pronouns, thus reducing the explanatory load for linguistic theories.
Sensitivity to Evidential Dependencies in Judgments Under Uncertainty
Authors: Xie Belinda , Hayes Brett
Published: May 2022

According to Bayesian models of judgment, testimony from independent informants has more evidential value than dependent testimony. Three experiments investigated learners' sensitivity to this distinction. Each experiment used a social version of the balls‐and‐urns task, in which participants judged which of two urns was the most likely source of evidence presented by multiple informants. Informants either provided independent testimony based solely on their own observations or dependent‐sequential testimony that considered the testimonies of previous informants. Although participants updated their beliefs with additional evidence, this updating was generally insensitive to evidential dependency (Experiments 1 and 2). A notable exception was when individuals were separated according to their beliefs about the relative value of independent and sequential evidence. Those who viewed independent evidence as having greater value subsequently gave more weight to independent testimony in the balls‐and‐urns task (Experiment 3), in line with the predictions of a Bayesian model. Our findings suggest that only a minority of individuals conform to Bayesian predictions in the relative weighting of independent and dependent evidence in judgments under uncertainty.
Using partition analysis as a facile method to derive net clearances
Authors: Korzekwa Ken , Yadav Jaydeep , Nagar Swati
Published: May 2022

Partition analysis has been described previously by W.W. Cleland to derive net rate constants and simplify the derivation of enzyme kinetic equations. Here, we show that partition analysis can be used to derive elimination and transfer (distribution) net clearances for use in pharmacokinetic models. For elimination clearances, the net clearance approach is exemplified with a mammillary two‐compartment model with peripheral elimination, and the established well‐stirred and full hepatic clearance models. The intrinsic hepatic clearance associated with an observed average hepatic clearance can be easily calculated with net clearances. Expressions for net transfer clearances are easily derived, including models with explicit membranes (e.g., monolayer permeability and blood–brain barrier models). Together, these approaches can be used to derive equations for physiologically based and hybrid compartmental/ physiologically based models. This tutorial describes how net clearances can be used to derive relationships for simple models as well as increasingly complex models, such as inclusion of active transport and target mediated processes.
Requiring help injecting among people who inject drugs in Toronto, Canada: Characterising the need to address sociodemographic disparities and substance‐use specific patterns
Authors: Mitra Sanjana , Kolla Gillian , Bardwell Geoff , Wang Rick , Sniderman Ruby , Mason Kate , Werb Dan , Scheim Ayden
Published: May 2022

Introduction

Those requiring help injecting are at an elevated risk of injection‐related injury and blood‐borne infections and are thus a priority group for harm reduction programs. As supervised consumption services (SCS) are scaled‐up across Canada, information on those who require help injecting is necessary to inform equitable service uptake. We characterised the sociodemographic, structural and drug use correlates of needing help injecting among a cohort of people who inject drugs in Toronto, Canada.

Methods

A cross‐sectional baseline survey was administered between November 2018 and March 2020. Unadjusted and multivariable logistic regression models examined associations with requiring help injecting in the past 6 months. A gender‐stratified sub‐analysis described characteristics of receiving help among those requiring it.

Results

Of 701 participants (31.0% cisgender women), 294 (41.9%) needed recent help injecting. In unadjusted analyses, being a racialised, non‐Indigenous person (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.13–2.86) or a cisgender woman (OR 1.72, 95% CI 1.24–2.39) were associated with needing help. In multivariable analyses, requiring assistance was associated with needing frequent help preparing drugs (adjusted OR [AOR] 9.52, 95% CI 4.78–21.28), fewer years since first injection (AOR for 1 year increase: 0.97, 95% CI 0.95–0.99) and injecting stimulants. Among those who required help, cisgender women reported needing assistance more often than cisgender men (P = 0.009).

Discussion and Conclusions

Over two‐fifths of the sample required help injecting; requiring assistance was associated with sociodemographic indicators and substance use‐specific patterns. Findings highlight the need to scale‐up educational resources for those who receive or provide help injecting, as well as SCS that accommodate onsite injection assistance.
S1‐Leitlinie Kontaktekzem
Authors: Dickel Heinrich , Bauer Andrea , Brehler Randolf , Mahler Vera , Merk Hans F. , Neustädter Irena , Strömer Klaus , Werfel Thomas , Worm Margitta , Geier Johannes
Published: May 2022

Das Kontaktekzem (syn.Kontaktdermatitis) ist eine durch äußere Einwirkungen ausgelöste Entzündung der Epidermis und der Dermis am Ort der Einwirkung. Die beiden Hauptformen sind das irritative und das allergische Kontaktekzem, die neben einer ausgeprägten Verminderung der Lebensqualität auch erhebliche gesundheits‐ und sozioökonomische Kosten verursachen. Wegweisend für die erforderlichen diagnostischen Maßnahmen sind die Anamnese und das klinische Bild. Eine möglichst genaue diagnostische Einordnung des Kontaktekzems mittels allergologischer Testung ist wichtig für das Krankheitsmanagement, da hier nicht nur die klassische Ekzemtherapie, sondern auch das Meiden der exogenen auslösenden Faktoren von großer Bedeutung sind. Die Wahl der Therapie sollte sich nach der Akuität, dem klinischen Schweregrad, der Morphologie der Läsionen und der Lokalisation des Kontaktekzems richten. Erforderlich ist eine bedarfsadaptierte Kombination aus Basistherapie, topischer, physikalischer und systemischer Therapie, wobei nicht alle Therapieformen gleichzeitig durchgeführt werden müssen, sondern variierend eingesetzt werden können. Primäre, sekundäre und tertiäre Präventionsstrategien zielen auf die Erkennung der auslösenden Noxen beziehungsweise der auslösenden Allergene mit nachfolgender Kontaktvermeidung oder ‐minimierung.

Die vorliegende S1‐Leitlinie zum Kontaktekzem soll vor allem Dermatologen, Allergologen sowie allergologisch und berufsdermatologisch tätigen Ärzten eine Entscheidungshilfe für die Auswahl sowie die Durchführung einer geeigneten und suffizienten Diagnostik, Therapie und Prävention zur Verfügung zu stellen.
The subtypes of developmental coordination disorder
Authors: Lust Jessica M. , Steenbergen Bert , Diepstraten Johanna (Ankie) E. M. , Wilson Peter H. , Schoemaker Marina M. , Poelma Margriet J.
Published: May 2022

Aim

To identify subtypes in a large group of children clinically diagnosed with developmental coordination disorder (DCD) based on their pattern of motor, cognitive, and visual‐motor abilities.

Method

Standardized scores for verbal IQ, total IQ, Movement Assessment Battery for Children, Second Edition (MABC‐2) balance, MABC‐2 manual dexterity, MABC‐2 ball skills, and Beery‐Buktenica Developmental Tests of Visual‐Motor Integration (Beery‐VMI), Motor Coordination (Beery‐MC), and Visual Perception (Beery‐VP) were used. The NbClust complete procedure was used to best partition the data on 98 children (84 males, 14 females, mean [SD] age: 8 years [2 years 1 month]) into clusters. Deviation contrasts, multivariate analysis of variance, and post hoc comparisons were used to characterize the clusters.

Results

Four clusters were revealed: two clusters with a broad motor skill problem, one with relatively preserved visual‐motor integration and Beery‐MC skills, and a second with abnormal ball skills, balance, and Beery‐MC skills. A third cluster with more specific gross‐motor problems, and a fourth with relatively preserved ball skills but low Beery‐MC and performance IQ, were identified. Balance scores were ‘at risk’ or ‘abnormal’ in all four clusters.

Interpretation

DCD is a heterogeneous condition. However, subtypes can be discriminated on the basis of more severe difficulties in fine‐motor performance, gross‐motor performance, or both. There was evidence for generalized motor impairments in around half of all children. Importantly, at least borderline level reduced balance was evident in each subtype.

What this paper adds

Four subtypes were identified in a large clinical group of children with developmental coordination disorder (DCD).

Subtypes were based on motor, cognitive, and visual‐motor abilities.

There was evidence of generalized motor impairments in around 50% of children with DCD.

A generalized balance problem is present across all subtypes of DCD.
Promoting openness to autism amongst dental care professional students
Authors: Mac Giolla Phadraig Caoimhin , Kahatab Ahmed , Daly Blánaid
Published: May 2022

Introduction

Autism spectrum disorders (ASD) is a lifelong condition affecting communication and social interaction, characterised by repetitive or repeated patterns of behaviour. People with ASD experience poor systemic and oral health. They face reduced access to dental care related to provider barriers associated with lack of understanding of ASD, lack of training and a consequent reluctance to treat people with ASD.

Materials and Methods

The effectiveness of training given by a person with autism to student dental care professionals was evaluated by measuring change in 62 students' openness to autism scale scores and confidence treating a person with autism. These students included third year dental students and second year dental nursing and hygiene students. This cohort was recruited as part of their curriculum and opted in for inclusion in the study. Data were analysed using SPSS®.

Results

An increase in openness scale scores of 7.6% (p < .05) and in confidence of 4.9% (p < .05) between pre‐ and post‐training was observed. Openness scale score predicted level of confidence at baseline (OR = 0.21 (95% CI = 0.02–0.39)).

Conclusion

An educational intervention delivered by a person with autism promoted modest increases in openness towards autism and confidence amongst dental care pre‐service professionals. Whilst the results suggest that peer‐led dental care professional teaching by people with autism may be beneficial, more research is needed.
Students' perception on flipped classroom with formative assessment: A focus group study
Authors: Othman Siti Adibah , Kamarudin Yasmin , Sivarajan Saritha , Soh Eunice Xinwei , Lau May Nak , Zakaria Nor Nadia , Wey Mang Chek , Wan Hassan Wan Nurazreena , Bahar Aufa Dahlia , Mohd Tahir Norhidayah @ Nor Zahidah, , Razi Roziana M. , Naimie Zahra
Published: May 2022

Objective

To explore students' perception on the implementation of flipped classroom (FC) combined with formative assessment during the undergraduate teaching of orthodontic wire‐bending skills.

Methods

Third‐year undergraduate dental students were taught wire‐bending skills via FC teaching method using a series of pre‐recorded online video demonstrations. As part of the formative assessment, the students were given the results and assessment rubrics of their prior wire‐bending assessment before every subsequent session. Purposive sampling method for focus group discussion was used to recruit eight students comprising four high achievers and four low achievers. Strengths, weaknesses and suggestions for improvement of the FC with formative assessment were explored. Data were transcribed and thematically analysed.

Results

Students perceived that FC allowed for a more convenient and flexible learning experience with personalised learning and improved in‐class teaching efficiency. The pre‐recorded online videos were useful to aid in teaching wire‐bending skills but lacked three‐dimensional representation of the wire‐bending process. Students suggested better standardisation of instructions and access to the marking rubric before and after assessment.

Conclusions

FC teaching with continuous formative assessment and constructive feedback as a form of personalised learning was viewed favourably by students. The implementation of periodic individual feedback can further enhance their learning experience.