bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfemoral interface considerations: A clinical consensus practice guideline
Authors: O'Brien Erin , Stevens Phillip M. , Miro Rebecca , Highsmith M. Jason
Published: November 2022

Background:

Although there have been a number of studies exploring the impact and efficacy of transfemoral prosthetic components such as knee and foot mechanisms, the empirical evidence surrounding transfemoral prosthetic interface considerations is limited. This constitutes a substantial void for practicing clinicians seeking to apply best practices for patients who use transfemoral prostheses. Recent years have seen increased production and availability of clinical practice guidelines germane to prosthetic rehabilitation. In those areas where empirical evidence is lacking, consensus clinical opinions may constitute the highest level of evidence.

Objective:

A consensus exercise was performed to generate clinical practice recommendations in the areas of transfemoral interface considerations including socket variations and critical design features, suspension and interface considerations, alignment, heat retention and dermatologic considerations, female considerations, surgical considerations, and both regulatory and ethical considerations related to osseointegration.

Methods:

This began with the generation of postulate items through systematic and narrative literature reviews. A Delphi consensus exercise was performed among clinical experts in government hospital and private clinical practice settings, culminating in a series of clinical practice recommendations associated with the prosthesis–limb interface for individuals with transfemoral amputation.

Results:

The completed recommendations include guidance statements relative to socket variations and critical design features, female considerations, suspension and interface considerations, surgical variations and prescription considerations, rehabilitation team considerations and both regulatory and ethical considerations related to osseointegration.

Conclusions:

The Delphi process facilitated the development of practice guidelines for transfemoral prosthetic interface considerations based on aggregated subject matter expertise.
Reconstructing horizontal gene flow network to understand prokaryotic evolution
Authors: Sengupta Soham , Azad Rajeev K.
Published: November 2022

Horizontal gene transfer (HGT) is a major source of phenotypic innovation and a mechanism of niche adaptation in prokaryotes. Quantification of HGT is critical to decipher its myriad roles in microbial evolution and adaptation. Advances in genome sequencing and bioinformatics have augmented our ability to understand the microbial world, particularly the direct or indirect influence of HGT on diverse life forms. Methods for detecting HGT can be classified into phylogenetic-based and parametric or composition-based approaches. Here, we exploited the complementary strengths of both the approaches to construct a high confidence horizontal gene flow network. Our network is unique in its ability to detect the transfer of native genes of a genome to genomes from other taxa, thus establishing donor and recipient organisms (taxa), rather than through a post hoc analysis as is the practice with several other approaches. The scale-free horizontal gene flow network presented here provides new insights into modes of transfer for the exchange of genetic information and also illuminates differential gene flow across phyla.
Blunt head impact causes a temperature rise in the brain
Authors: Madhukar Amit , Ostoja-Starzewski Martin
Published: November 2022

A magnetic resonance imaging-based finite-element model is employed to assess the temperature in the human brain due to blunt head trauma. The model is based on a coupled thermoelasticity under small strain and Fourier or Maxwell–Cattaneo heat conduction assumptions, accompanied by a standard coupling of thermal fields to mechanics. It is found that mechanical impacts on the forehead cause a temperature rise of up to 0.3°C above the reference homogeneous temperature field.
Registered reports in forensic science
Authors: Houck M. M. , Chin J. , Swofford H. , Gibb C.
Published: November 2022

Research assessing the validity and reliability of many forensic science disciplines has been published; however, the quality of this research varies depending on the methodologies employed. This was a major point of contention with the United States' President's Council of Advisors on Science and Technology, who recognized the existing literature but found the majority lacking because of methodological issues. Questionable scientific methodologies have undermined the forensic science community's ability to defend the scientific foundations and examination protocols used to examine evidence in criminal cases. Such scientific failures have significant legal implications. Registered reports, which strengthen the quality of scientific research and reliability of laboratory protocols, can provide transparency, validity and a stronger scientific foundation for forensic science.
Nutrigonometry III: curvature, area and differences between performance landscapes
Authors: Morimoto Juliano , Conceição Pedro , Smoczyk Knut
Published: November 2022

Nutrition is one of the underlying factors necessary for the expression of life-histories and fitness across the tree of life. In recent decades, the geometric framework (GF) has become a powerful framework to obtain biological insights through the construction of multidimensional performance landscapes. However, to date, many properties of these multidimensional landscapes have remained inaccessible due to our lack of mathematical and statistical frameworks for GF analysis. This has limited our ability to understand, describe and estimate parameters which may contain useful biological information from GF multidimensional performance landscapes. Here, we propose a new model to investigate the curvature of GF multidimensional landscapes by calculating the parameters from differential geometry known as Gaussian and mean curvatures. We also estimate the surface area of multidimensional performance landscapes as a way to measure landscape deviations from flat. We applied the models to a landmark dataset in the field, where we also validate the assumptions required for the calculations of curvature. In particular, we showed that linear models perform as well as other models used in GF data, enabling landscapes to be approximated by quadratic polynomials. We then introduced the Hausdorff distance as a metric to compare the similarity of multidimensional landscapes.
Normal forms for saddle-node bifurcations: Takens’ coefficient and applications in climate models
Authors: Glendinning P. A. , Simpson D. J. W.
Published: November 2022

We show that a one-dimensional differential equation depending on a parameterμwith a saddle-node bifurcation atμ=0can be modelled by an extended normal formy˙=ν(μ)−y2+a(μ)y3,where the functionsνandaare solutions to equations that can be written down explicitly. The equivalence to the original equations is a local differentiable conjugacy on the basins of attraction and repulsion of stationary points in the parameter region for which these exist, and is a differentiable conjugacy on the whole local interval otherwise. (Recall that in standard approaches local equivalence is topological rather than differentiable.) The valuea(0)is Takens’ coefficient from normal form theory. The results explain the sense in which normal forms extend away from the bifurcation point and provide a new and more detailed characterization of the saddle-node bifurcation. The one-dimensional system can be derived from higher dimensional equations using centre manifold theory. We illustrate this using two examples from climate science and show how the functionsνandacan be determined analytically in some settings and numerically in others.
The serotonin circuit that coordinates germline proliferation and egg laying with other reproductive functions in
Caenorhabditis elegans
Authors: Aprison Erin Z. , Dzitoyeva Svetlana , Ruvinsky Ilya
Published: November 2022

Behaviour and physiology are altered in reproducing animals, but neuronal circuits that regulate these changes remain largely unknown. Insights into mechanisms that regulate and possibly coordinate reproduction-related traits could be gleaned from the study of sex pheromones that can improve the reproductive success of potential mating partners. In
Caenorhabditis elegans
, the prominent male pheromone, ascr#10, modifies reproductive behaviour and several aspects of reproductive physiology in hermaphrodite recipients, including improving oocyte quality. Here we show that a circuit that contains serotonin-producing and serotonin-uptaking neurons plays a key role in mediating effects of ascr#10 on germline development and egg laying behaviour. We also demonstrate that increased serotonin signalling promotes proliferation of germline progenitors in adult hermaphrodites. Our results establish a role for serotonin in maintaining germline quality and highlight a simple neuronal circuit that acts as a linchpin that couples food intake, mating behaviour, reproductive output, and germline renewal and provisioning.
Among-species variation in hormone concentrations is associated with urban tolerance in birds
Authors: Sinclair Emma C. C. , Martin Paul R. , Bonier Frances
Published: November 2022

As cities expand across the globe, understanding factors that underlie variation in urban tolerance is vital for predicting changes in patterns of biodiversity. Endocrine traits, like circulating hormone concentrations and regulation of endocrine responses, might contribute to variation in species' ability to cope with urban challenges. For example, variation in glucocorticoid and androgen concentrations has been linked to life-history and behavioural traits that are associated with urban tolerance. However, we lack an understanding of the degree to which evolved differences in endocrine traits predict variation in urban tolerance across species. We analysed 1391 estimates of circulating baseline corticosterone, stress-induced corticosterone, and testosterone concentrations paired with citizen-science-derived urban occurrence scores in a broad comparative analysis of endocrine phenotypes across 71 bird species that differ in their occurrence in urban habitats. Our results reveal context-dependent links between baseline corticosterone and urban tolerance, as well as testosterone and urban tolerance. Stress-induced corticosterone was not related to urban tolerance. These findings suggest that some endocrine phenotypes contribute to a species’ tolerance of urban habitats, but also indicate that other aspects of the endocrine phenotype, such as the ability to appropriately attenuate responses to urban challenges, might be important for success in cities.
Gene transferability and sociality do not correlate with gene connectivity
Authors: Hao Chunhui , Dewar Anna E. , West Stuart A. , Ghoul Melanie
Published: November 2022

The connectivity of a gene, defined as the number of interactions a gene's product has with other genes' products, is a key characteristic of a gene. In prokaryotes, the complexity hypothesis predicts that genes which undergo more frequent horizontal transfer will be less connected than genes which are only very rarely transferred. We tested the role of horizontal gene transfer, and other potentially important factors, by examining the connectivity of chromosomal and plasmid genes, across 134 diverse prokaryotic species. We found that (i) genes on plasmids were less connected than genes on chromosomes; (ii) connectivity of plasmid genes was not correlated with plasmid mobility; and (iii) the sociality of genes (cooperative or private) was not correlated with gene connectivity.
Experimental reduction of haemosporidian infection affects maternal reproductive investment, parental behaviour and offspring condition
Authors: Schoepf Ivana , Olson Sarena , Moore Ignacio T. , Bonier Frances
Published: November 2022

When hosts have a long coevolutionary history with their parasites, fitness costs of chronic infection have often been assumed to be negligible. Yet, experimental manipulation of infections sometimes reveals effects of parasites on their hosts, particularly during reproduction. Whether these effects translate into fitness costs remains unclear. Here, we present the results of an experimental study conducted in a free-ranging population of red-winged blackbirds (Agelaius phoeniceus) naturally experiencing a high prevalence of haemosporidian infections, with more than 95% of breeding adults infected with parasites from one or more haemosporidian genus. To assess effects of infection during reproduction, we manipulated adult red-winged blackbird females’ parasite burden by administering an anti-haemosporidian medication before onset of egg-laying. Experimental reduction of infection resulted in significant benefits to mothers and their offspring. Medicated females laid heavier clutches, invested more in incubation and provisioning behaviour, and produced more fledglings than control females. Nestlings of medicated females had higher haematocrit, higher blood glucose, and lower reactive oxygen metabolites than nestlings of control females. Overall, our results provide evidence that, even in a species with high prevalence of infection, parasites can lead to decreased maternal investment and offspring quality, substantially reducing fitness.
On the function of flower number: disentangling fertility from pollinator-mediated selection
Authors: Barbot Estelle , Dufaÿ Mathilde , Tonnabel Jeanne , Godé Cécile , De Cauwer Isabelle
Published: November 2022

In animal-pollinated angiosperms, the ‘male-function’ hypothesis claims that male reproductive success (RS) should benefit from large floral displays, through pollinator attraction, while female RS is expected to be mainly limited by resource availability. As appealing as this theory might be, studies comparing selection strength on flower number in both sexes rarely document the expected asymmetry. This discrepancy could arise because flower number impacts both pollinator attraction and overall gamete number. In this study, we artificially manipulate floral displays to disentangle the fertility versus pollinator attraction components of selection, both in terms of mating and RS. In females, flower number was under strong fertility selection, as predicted in the absence of pollen limitation. By contrast, in males, flower number was mainly under sexual selection, which in turn increased male RS. However, these selection patterns were not different in males with artificially increased floral displays. This suggests that sexual selection acting on flower number in males does not occur because flower number increases pollinator attraction, but rather because more pollen is available to disperse on more mates. Our study illustrates the power of disentangling various components of selection with potentially sex-specific effects for understanding the evolution of sexual dimorphism.
Managing the effects of multiple stressors on wildlife populations in their ecosystems: developing a cumulative risk approach
Authors: Tyack Peter L. , Thomas Len , Costa Daniel P. , Hall Ailsa J. , Harris Catriona M. , Harwood John , Kraus Scott D. , Miller Patrick J. O. , Moore Michael , Photopoulou Theoni , Pirotta Enrico , Rolland Rosalind M. , Schwacke Lori H. , Simmons Samantha E. , Southall Brandon L.
Published: November 2022

Assessing cumulative effects of human activities on ecosystems is required by many jurisdictions, but current science cannot meet regulatory demands. Regulations define them as effect(s) of one human action combined with other actions. Here we argue for an approach that evaluates the cumulative risk of multiple stressors for protected wildlife populations within their ecosystems. Monitoring effects of each stressor is necessary but not sufficient to estimate how multiple stressors interact to affect wildlife populations. Examining the mechanistic pathways, from cellular to ecological, by which stressors affect individuals can help prioritize stressors and interpret how they interact. Our approach uses health indicators to accumulate the effects of stressors on individuals and to estimate changes in vital rates, driving population status. We advocate using methods well-established in human health and integrating them into ecosystem-based management to protect the health of commercially and culturally important wildlife populations and to protect against risk of extinction for threatened species. Our approach will improve abilities to conserve and manage ecosystems but will also demand significant increases in research and monitoring effort. We advocate for increased investment proportional to the economic scale of human activities in the Anthropocene and their pervasive effects on ecology and biodiversity.
Plasmids of the urinary microbiota
Authors: Johnson Genevieve , Bataclan Seanna , So Minerva , Banerjee Swarnali , Wolfe Alan J. , Putonti Catherine
Published: November 2022

Studies of the last decade have identified a phylogenetically diverse community of bacteria within the urinary tract of individuals with and without urinary symptoms. Mobile genetic elements (MGEs), including plasmids and phages, within this niche have only recently begun to be explored. These MGEs can expand metabolic capacity and increase virulence, as well as confer antibiotic resistance. As such, they have the potential to contribute to urinary symptoms. While plasmids for some of the bacterial taxa found within the urinary microbiota (urobiome) have been well characterized, many urinary species are under-studied with few genomes sequenced to date. Using a two-pronged bioinformatic approach, we have conducted a comprehensive investigation of the plasmid content of urinary isolates representative of 102 species. The bioinformatic tools plasmidSPAdes and Recycler were used in tandem to identify plasmid sequences from raw short-read sequence data followed by manual curation. In total, we identified 603 high-confidence plasmid sequences in 20 different genera of the urobiome. In total, 70 % of these high-confidence plasmids exhibit sequence similarity to plasmid sequences from the gut. This observation is primarily driven by plasmids from

E. coli

, which is found in both anatomical niches. To confirm our bioinformatic predictions, long-read sequencing was performed for 23 of the

E. coli

isolates in addition to two

E. coli

strains that were sequenced as part of a prior study. Overall, 66.95 % of these predictions were confirmed highlighting the strengths and weaknesses of current bioinformatic tools. Future studies of the urobiome, especially concerning under-studied species in the urobiome, should employ long-read sequencing to expand the catalogue of plasmids for this niche.
Cognitive Interview Validation of a Novel Household Hazard Vulnerability Assessment Instrument
Authors: Amberson Taryn , Ndayishimiye Olive , Cloud Quanah Yellow , Castner Jessica
Published: November 2022

Background

Weather and climate disasters are responsible for over 13,000 USA deaths, worsened morbidity, and $1.7 trillion additional costs over the last 40 years with profound racial disparities. This project empirically generated items for a novel survey instrument of household hazard vulnerability with initial construct validation while addressing racial data bias.

Methods

Cognitive interviewing methodology was completed with transdisciplinary disaster expert panelists (n=20) from diverse USA regions on 60 unique hazard, disaster, or event items. Interview video recordings were qualitatively analyzed using thematic and pattern coding.

Results

A cognitive process mapped to themes of disaster characteristics, resources, individual life facet, and felt effect was revealed. 379 unique instances of linked terms as synonyms, co-occurring, compounding, or cascading events were identified. Potential for racial data bias was elucidated. Analysis of radiation exposure, trauma, criminal acts of intent items revealed participants may not interpret survey items with these terms as intended.

Discussion

The findings indicate the potential for racial data bias relative to water dam failure, evacuation, external flood, suspicious package/substance, and transportation failure. Hazard terms that were not interpreted as intended require further revision in the validation process of individual or household disaster vulnerability assessments.

Conclusion

Several commonalities in the cognitive process and mapping of disaster terms may be utilized in disaster and climate change research aimed at the individual and household unit of analysis.

Highlights

⍰

Older adults and those with Black/African American racial identities are particularly susceptible to post-disaster health sequelae.

⍰

Prior to this study, no household-level Hazard Vulnerability Analysis existed. Quantifying risk for at-risk individuals/groups is a necessary initial step for working to eliminate disparities in large-scale disaster health outcomes.

⍰

Our findings indicate the potential for racial data bias relative to water dam failure, evacuation, external flood, suspicious package/substance, and transportation failure. Overall, several hazard, disaster, and event terms were not interpreted by survey-takers as intended, which may require elimination, replacement, or further revision in the validation process of individual or household assessments.
Segment and Slice: A Two-Step Deep Learning Pipeline for Opportunistic Vertebral Fracture Detection in Computed Tomography
Authors: Glessgen Carl G. , Cyriac Joshy , Yang Shan , Manneck Sebastian , Wichtmann Hildegard , Wasserthal Jakob , Kovacs Balazs K. , Harder Dorothee
Published: November 2022

Objectives

An end-to-end method is introduced to build a combined segmentation-classification pipeline using deep learning for opportunistic fracture detection in CT spine images of varying field-of-views.

Materials and Methods

This retrospective study builds on 452 CTs of the lumbar/thoracolumbar spine. Patients were included based on the evidence of ≥ 1 vertebral body fracture and excluded in case of history of spinal surgery or pathologic fractures. The collective was split into training/validation (405) and test (47) sets. An open-source pre-segmented spine dataset was used to train a preliminary segmentation model, which was applied on the training set. The resulting segmentation was post-processed to remove posterior vertebral structures and if needed manually refined by a radiologist. Using the refined version as new training data, a final segmentation nnU-net was trained. Sagittal slices from each vertebra were labelled individually with regard to fracture evidence. Slices without signs of fracture were used as negative class. 27,019 slices (20,396 negative, 6,623 positive) trained a classification algorithm using resnet18. Two senior readers independently assessed fractures in the test set to obtain a consensual ground truth. The segmentation-classification pipeline was applied to the test set and compared to the ground truth.

Results

The segmentation model correctly segmented 330/339 (97%) vertebrae. Considering every segmented vertebra, the classifier detected fractures with 88% sensitivity, 95% specificity and 93% accuracy.

Conclusion

Our two-step method can help to detect spine fractures on images of varying field-of-views, with an accuracy comparable to that of a radiologist in-training. The final models as well as our code material are available athttps://github.com/usb-radiology/VertebraeFx.
A scoping review of virtual morning report and outcomes in Canada and the United States
Authors: Sarma Shohinee , Kanagalingam Tharsan , Lai James , Ahmad Tehmina
Published: November 2022

Purpose

To describe the current landscape of virtual morning report (VMR) in medical residency education including its varying formats, methods, and associated effectiveness on learning and clinical outcomes.

Methods

The authors conducted a scoping review using the Arksey and O’Malley methodology. They searched Embase, OvidMEDLINE, Google Scholar, and PubMed between January 1, 1991 to April 15, 2022. Articles written in English on virtual morning report and virtual case-based teaching in medical residency programs were captured. Two authors independently screened articles using the inclusion criteria. Using a snowball approach, further citations were identified from included references. Two authors performed data extraction including outcomes using the Kirkpatrick model. We conducted thematic analysis using an iterative process.

Results

A total of 401 citations were screened for eligibility and we included 40 articles. The number of published studies per year on VMR increased since the COVID-19 pandemic. Most studies used online case-based modules (n=20; 50.0%) or videoconferencing (n=12; 30.0%). The majority of studies described improved confidence with clinical reasoning, easy access, and preference for chatboxes/polls for engagement (Kirpatrick level 1). Nineteen studies demonstrated improved knowledge acquisition with pre-and post-test scores (Kirkpatrick level 2). Behaviour changes (Kirkpatrick level 3) included improved screening tests and medication prescribing. There were no studies on clinical outcomes (Kirkpatrick level 4). Thematic analyses revealed that VMR increased clinical reasoning, efficiently used technology, provided an inclusive environment for diverse learners, but reduced peer engagement and bedside teaching.

Conclusion

Virtual morning report has a positive impact on learner confidence, knowledge, inclusivity, accessibility, and behaviour change. Future research is needed to explore the impact on patient outcomes as well as identify strategies for peer engagement and social interaction.
Developing a research ready population-scale linked data ethnicity-spine in Wales
Authors: Akbari Ashley , Torabi Fatemeh , Bedston Stuart , Lowthian Emily , Abbasizanjani Hoda , Fry Richard , Lyons Jane , Owen Rhiannon K , Khunti Kamlesh , Lyons Ronan A
Published: November 2022

Introduction Ethnicity information is recorded routinely in electronic health records (EHRs); however, to date, there is no national standard or framework for harmonisation of the existing records. Methods and analysis The national ethnicity-spine uses anonymised individual-level population-scale ethnicity data from 26 EHR available through the Secure Anonymised Information Linkage (SAIL) Databank. A total of 46 million ethnicity records for 4,297,694 individuals in Wales-UK over 22 years (between 2000 and 2021) have been compiled in a harmonised, deduplicated longitudinal research ready data asset. We serialised this data and compared distribution of records over time for four selection approaches (Latest, Mode, Weighted-Mode and Composite) across age bands, sex, deprivation quintiles, health board, and residential location, against the ONS census 2011. The distribution of the dominant group (White) is minimally affected based on the four different selection approaches. Across all other ethnicity categorisations, the Mixed group was most susceptible to variation in distribution depending on the selection approach used and varied from a 0.6% prevalence across the Latest and Mode approach to a 1.1% prevalence for the Weighted-Mode, compared to the 3.1% prevalence for the Composite approach. Substantial alignment was observed with ONS census with the Latest group method (kappa= 0.68, 95% CI [0.67,0.71]) across all sub-groups. Conclusion We provides a reproducible EHR based resource enabling the investigation and evaluation of health inequalities related to ethnic groups in Wales. This generalisable method informs opportunities for the transferability of this methodology across the UK to platforms with comparable routine data sources. Ethics and dissemination This work was supported by the Con-COV team funded by Medical Research Council, Health Data Research UK, ADR Wales funded by ADR UK through the Economic and Social Research Council, and the Wales COVID-19 Evidence Centre, funded by Health and Care Research Wales.
Determinants of catastrophic health expenditure attributable to non-communicable diseases and impoverishment in Pakistan
Authors: Naz Lubna , Sriram Shyamkumar , Sardar Filzah
Published: November 2022

Background

Pakistan has a disproportionately high burden of non-communicable diseases (NCDs), leading to an increase in healthcare utilization and associated out-of-pocket health expenditure, adversely affecting the well-being of the household. This study aims to identify the determinants of catastrophic health expenditure (CHE) on NCDs and quantify the impoverishment effects of OOP expenditure attributable to NCDs.

Methods

The study used Household Integrated Economic Survey - 2018/2019 and the National Health Accounts Data 2017. The welfare impact of out-of-pocket health spending associated with NCDs was assessed using specific measures: a) incidence and intensity of catastrophic health expenditure and b) the impoverishing effect. A generalized linear model with a logit link function was used to study the determinants of CHE at different thresholds.

Results

The poverty headcount was 20.5% without accounting for OOP expenditure for NCDs; with adjustment, it increased to 27%, causing 13 million (from 42.4 million to 55.6) more people to fall into poverty. Households experiencing CHE fell from 60% to 3.5% as the threshold increased from 10% to 40%, implying fewer households encounter CHE at higher thresholds. Larger families, male-headed, families with children and older members, having more members with NCDs, and using private healthcare were more likely to incur CHE.

Conclusions

CHE has a high propensity to push households into poverty. Pakistan’s National Health Vision 2016-2025 recognizing the provision of Universal Health Coverage and poverty alleviation as the top health and social priorities needs to be implemented to achieve Sustainable Development Goal targets of UHC and financial risk protection.

Key messages

Household’s out-of-pocket spending associated with non-communicable disease was USD19 per month.

Female headed families had a lower likelihood of incurring catastrophic health expenditure on NCDs than the male.

Only a fewer households encountered catastrophic health expenditure at higher thresholds.

Rural households had a higher impoverishing effect of out-of-pocket expenditure associated with NCDs compared to the urban.
Paediatric snakebite in Kilifi County, Kenya: A 19-year observational study
Authors: Abouyannis Michael , Boga Mwanamvua , Amadi David , Ouma Nelson , Nyaguara Amek , Mturi Neema , Berkley James A. , Adetifa Ifedayo , Casewell Nicholas R , Lalloo David G , Hamaluba Mainga
Published: November 2022

Introduction

Estimates suggest that one-third of snakebite cases in sub-Saharan Africa affect children. Despite children being at a greater risk of disability and death, there are limited published data describing the burden of paediatric snakebite. This study describes the clinical features, hospital management, population-incidence, and mortality of consecutive paediatric snakebite cases over a 19-year period.

Methods

Using the Kilifi Health and Demographic Surveillance System (KHDSS), all children with snakebite presenting to Kilifi County Hospital were identified. All cases were prospectively registered, admitted for at least 24-hours, and managed on a paediatric high dependency unit (HDU). Households within the KHDSS study area have been included in 4-monthly surveillance and verbal autopsy, enabling calculation of population-incidence and mortality. Predictors of severe local tissue damage were identified using a multivariate logistic regression analysis.

Results

Between 2003 and 2021, there were 19,798 admissions to the paediatric HDU, of which 619 were due to snakebite. Amongst infants (≤5-years age) the population-incidence of hospital-attended snakebite was 9.8/100,000 person-years; for children aged 6-13-years this was 26.4/100,000 person-years. The number of children attending hospital with snakebite has increased over time. Children aged 8-11 years had the highest incidence. There were six snakebite associated deaths. At admission, low haemoglobin, raised white blood cell count, and an upper limb bite-site were associated with the development of severe local tissue damage.

Conclusion

There is a substantial burden of disease due to paediatric snakebite and this has increased in-line with population growth. Most cases present with local rather than systemic envenoming, and many of these receive antivenom. The mortality rate was low, which may reflect the quality of care delivered on the paediatric HDU. There is an urgent need to better define the burden of paediatric snakebite across Africa, to initiate community engagement to prevent snakebites, and to improve treatments for local tissue damage.
Myeloid-specific KDM6B inhibition sensitizes Glioblastoma to PD1 blockade
Authors: Goswami Sangeeta , Raychaudhuri Deblina , Singh Pratishtha , Natarajan Seanu Meena , Chen Yulong , Poon Candice , Hennessey Mercedes , Zhang Jan , Anandhan Swetha , Kerrigan Brittany Parker , Macaluso Marc D. , He Zhong , Jindal Sonali , Lang Frederick F. , Basu Sreyashi , Sharma Padmanee
Published: November 2022

Glioblastoma (GBM) tumors are enriched in immune-suppressive myeloid cells and are refractory to immune checkpoint therapy (ICT). Targeting epigenetic pathways to reprogram the functional phenotype of immune-suppressive myeloid cells to overcome resistance to ICT remains unexplored. Single-cell and spatial transcriptomic analyses of human GBM tumors demonstrated high expression of an epigenetic enzyme - histone 3 lysine 27 demethylase (KDM6B) in intra- tumoral immune-suppressive myeloid cell subsets. Importantly, myeloid-cell specificKdm6bdeletion enhanced pro-inflammatory pathways and improved survival in GBM tumor-bearing mice. Mechanistic studies elucidated that the absence ofKdm6benhances antigen-presentation, interferon response and phagocytosis in myeloid cells by inhibiting mediators of immune suppression includingMafb, Socs3andSirpa. Further, pharmacological inhibition of KDM6B mirrored the functional phenotype ofKdm6bdeleted myeloid cells and enhanced anti-PD1 efficacy. Thus, this study identified KDM6B as an epigenetic regulator of the functional phenotype of myeloid cell subsets and a potential therapeutic target to improve response to ICT.
A simple within-host, between-host model for a vector-transmitted disease
Authors: Núñez-López Mayra , Castro-Echeverría Jocelyn A. , Velasco-Hernández Jorge X.
Published: November 2022

We present a model that explicitly links the epidemiological Ross-Macdonald model with a simple immunological model through a virus inoculation term that depends on the abundance of infected mosquitoes. We explore the relationship between the reproductive numbers at the population (between-host) and individual level (within-host), in particular the role that viral load and viral clearance rate play in the coupled dynamics. Our model shows that under certain conditions on the strength of the coupling and the immunological response of the host, there can be sustained low viral load infections, with a within-host reproduction number below one that still can trigger epidemic outbreaks provided the between host reproduction number is greater than one. We also describe a particular kind of transmission-clearance trade off for vector-host systems with a simple structure.
Multimodal MALDI imaging mass spectrometry for improved diagnosis of melanoma
Authors: Zhang Wanqiu , Patterson Nathan Heath , Verbeeck Nico , Moore Jessica L. , Ly Alice , Caprioli Richard M. , De Moor Bart , Norris Jeremy L. , Claesen Marc
Published: November 2022

Imaging mass spectrometry (IMS) provides promising avenues to augment histopathological investigation with rich spatio-molecular information. We have previously developed a classification model to differentiate melanoma from nevi lesions based on IMS protein data, a task that is challenging solely by histopathologic evaluation.

Most IMS-focused studies collect microscopy in tandem with IMS data, but this microscopy data is generally omitted in downstream data analysis. Microscopy, nevertheless, forms the basis for traditional histopathology and thus contains invaluable morphological information. In this work, we developed a multimodal classification pipeline that uses deep learning, in the form of a pre-trained artificial neural network, to extract the meaningful morphological features from histopathological images, and combine it with the IMS data.

To test whether this deep learning-based classification strategy can improve on our previous results in classification of melanocytic neoplasia, we utilized MALDI IMS data with collected serial H&E stained sections for 331 patients, and compared this multimodal classification pipeline to classifiers using either exclusively microscopy or IMS data. The multimodal pipeline achieved the best performance, with ROC-AUCs of 0.968 vs. 0.938 vs. 0.931 for the multimodal, unimodal microscopy and unimodal IMS pipelines respectively. Due to the use of a pre-trained network to perform the morphological feature extraction, this pipeline does not require any training on large amounts of microscopy data. As such, this framework can be readily applied to improve classification performance in other experimental settings where microscopy data is acquired in tandem with IMS experiments.
Urinary Extracellular vesicles abundance of SLC12A3 (NCC) increase and Aquaporine2 decrease following DASH diet implementation
Authors: Bielopolski Dana , Musante Luca , Molina Henrik , Barrows Douglas , Carrol Thomas , Tobin Jonathan N. , Kost Rhonda. G , Erdbruegger U
Published: November 2022

The Dietary Approach to Stop Hypertension (DASH) diet is a proven intervention to treat hypertension, yet its mechanism is not clearly known. We investigated the change in protein abundance patterns in urine extracellular vesicles (uEV’s) following DASH diet implementation.

A pilot study was carried out to compare uEVs isolated using three different methods: a low centrifugation (P20), high centrifugation (P100), and a combination of both (P20 and P100). Uromodulin was removed by size exclusion chromatography and low ionic strength washing. Mass spectrometry analysis identified 1,593 proteins in the combined fraction (P20+P100), 1434 in the P20 fraction and 1229 in the P100 fraction. The combined fraction was chosen for further analysis. Statistical analysis was carried out using R and Limma to identify all proteins that changed before and during 11 days of DASH intervention (p < 0.05) as well as between individual timepoints.

Nine hypertensive volunteers were admitted for a 14-day supervised transition from American style diet to DASH diet. First-void urine was collected on days 0, 5, 11 for uEV processing. In total, 1800 proteins were identified across all 27 DASH samples with 22 proteins upregulated and 25 down regulated between day 0 and both days 5 and 11. These included increased abundance of SLC12A3 (NCC) and reduced abundance of Aquaporine 2.

These changes could explain the increased urine volume and reduced sodium reabsorption that lead to blood pressure reduction following consumption of the high potassium and low sodium DASH diet. uEVs may serve as a surrogate to a more invasive procedure.

Translational Statement

Myriad studies have characterized blood pressure reduction following DASH diet implementation, yet its precise mechanism is unclear. Here, we demonstrate for the first time the effect of DASH nutritional changes, on kidney ion channel composition using proteomic analysis of urinary EVs. Using this innovative tool as a substitute for an invasive procedure, we show that the expression of Aquaporine2 increases and NCC decreases in response to DASH which may account for its antihypertensive effect. Our results indicate that urinary EV are a potential biomarker for DASH compliance, and targeting aquaporine2 may be an effective innovative therapeutic strategy for blood pressure reduction.
Polyvalent mRNA vaccination elicited potent immune response to monkeypox surface antigens
Authors: Fang Zhenhao , Renauer Paul A. , Suzuki Kazushi , Chen Sidi
Published: November 2022

The soaring global monkeypox cases lead to a surge in demand for monkeypox vaccine, which far exceeds the supply. mRNA vaccine has achieved great success in prevention of coronavirus disease and holds promise against diverse pathogens. In this study, we generate a polyvalent lipid nanoparticle (LNP) mRNA vaccine candidate for monkeypox virus (MPXV) and evaluate its immunogenicity in animal models. This polyvalent MPXV mRNA vaccine candidate, MPXVac-097, encodes five 2022 MPXV targets that are important surface antigens. Three-dose (prime-boost-booster) MPXVac-097 vaccination elicits strong antibody response to A35R and E8L antigens, moderate response to M1R, but not B6R or A29, highlighting the differences in immunogenicity. Bulk T cell receptor (TCR) sequencing reveals preferential usage of VJ combinations and clonal expansion of peripheral T cells after MPXVac-097 vaccination. These data demonstrate initial feasibility of developing MPXV mRNA vaccine and pave the way for its future optimization.
Strategic positioning of projects in crowdfunding platforms: do advanced technology terms referencing, signaling and articulation matter?
Authors: Zheng Yilong , Wang Yiru , Mian Sarfraz A.
Published: November 2022

Purpose

Tracking trends in new technology funding patterns is essential for venture scaling. The emerging advanced digital technologies (ADT) such as virtual reality (VR), artificial intelligence (AI), blockchain and Internet-of-things (IoT) promote business innovation adaptations, and in turn, reshape the industrial landscape. To attract nascent funding for such prospective projects among the public, well-articulated project pitches that are equipped with effective marketing communication convey the projects' importance and marketability. Specifically, when the entrepreneurs and the crowdfunding platform users interact via different types of crowdfunding platforms, pitch framing, including the signaling of ADT terms, project location and fundraising goal, becomes imperative to help facilitate crowdfunding success.

Design/methodology/approach

Drawing on data collected from six leading US-based equity and reward-based crowdfunding platforms in 2020, an empirical study was performed. Using the text analysis approach, the authors examined the positive effects of incorporating technology orientation on crowdfunding success. While the effect between the project description's signaling of geographic location, fundraising goal and articulation style on fundraising success, while controlling for project and platform characteristics.

Findings

The results suggested that the technology-orientated projects are more likely to achieve better fundraising outcomes. Taking crowdfunding platform types, project locations, minimum fundraising goals and articulation with analytical and authentic into consideration, the results still hold.

Originality/value

Building on the theoretical framework of signaling theory, the authors consider the crowdfunding-specific contextual factors to enhance the understanding of the positivity impact of technology orientation. By such addition, it facilitates more effective strategic composition of entrepreneurs' fundraising conversations.
From what we know to what we do: Human resource management intervention to support mode 2 healthcare research
Authors: Currie Graeme , Spyridonidis Dimitrios
Published: November 2022

There is a huge volume of evidence about what is clinically effective and efficient, but this is slow to translate into frontline practice. To address the problem, we need to support clinical academics and practitioners to co‐produce research and service improvement; necessitating HRM intervention. Our case study shows common purpose in mode 2 research across clinical academics and practitioners can be attained by focussing upon their professional identity, within which their status and jurisdictional autonomy are key dimensions. Our study shows how development workshops, through which control is ceded by managers to clinical academics and practitioners, are used to co‐design HRM interventions to support mode 2 research. Relevant HRM interventions are first, performance management that is non‐intrusive and aligns with criteria clinical academics and practitioners value. Second, job design that allows autonomy and status enhancement for clinical academics and practitioners engaging in mode 2 research.
Invasion of the coccinellid community associated with a tropical annual agroecosystem
Authors: Andow David A. , Fontes Eliana M. G. , Pires Carmen S. S. , Souza Lucas M. , Paula Débora P.
Published: November 2022

Detailed understanding of the mechanisms enabling or limiting the impacts of invasive generalist predators is needed. Harmonia axyridis is an invasive generalist coccinellid predator that may have destabilised coccinellid communities worldwide and is an excellent candidate for investigating invasion dynamics.

We evaluated four hypotheses: (1) Nine years after being detected in Central Brazil, Ha. axyridis has dominated the coccinellid community. This is facilitated by (2) its broader aphid prey range than the other aphidophagous coccinellids, (3) its superiority as an asymmetrical intraguild predator, and (4) the invasibility of the present coccinellid community.

We sampled the invertebrate communities associated with six organic vegetable farms in Brazil during 2017 and 2018, conducted a feeding trial to measure prey niche breadth and overlap, and estimated intra‐ and interspecific interaction strengths corresponding to first‐order Lotka‐Volterra parameters to evaluate the strength of intraguild predation and create a community matrix.

We found (1) Ha. axyridis comprised ≤8.3% of the coccinellid community. (2) Hi. convergens had the broadest prey niche and dominated the prey niche of Ha. axyridis. (3) We could not determine from the population data if Ha. axyridis was the dominant intraguild predator because its density was too low and constant. (4) The community matrix indicated that the present‐day coccinellid community was stable.

We conclude Ha. axyridis has not become invasive in Central Brazil, in part because it does not have the broadest prey niche breadth and the present coccinellid community is stable to the present perturbation of Ha. axyridis.
Prevalence and factors associated with pressure injury in patients undergoing open heart surgery: A systematic review and meta‐analysis
Authors: Taghiloo Hamed , Ebadi Abbas , Saeid Yaser , Jalali Farahni Alireza , Davoudian Atefeh
Published: November 2022

Pressure injuries (PIs) are one of the major and costliest medical problems with severe implications for patients. Cardiovascular surgery patients are at the higher risk of developing surgery‐related PIs. So this study was conducted with the aim of investigating the prevalence and factors associated with PIs in patients undergoing open heart surgery. We identified articles through electronic databases such as Web of Science, Scopus, PubMed, ProQuest; and Persian Databases: SID, Magiran and Irandoc without restriction on language or publication period (from inception through June 2022). Finally, 17 studies that fulfilled eligibility criteria were included in final systematic review and meta‐analysis. Data analyses were conducted using STATA version 14. The pooled prevalence of PI in patients undergoing open heart surgery was 24.06% (95% CI: 17.85–30.27). High heterogeneity was observed across the included studies (I2 = 96.0, P < 0.000). The prevalence by gender was reported as 25.19% (95% CI: 13.45–36.93) in men and 33.36% (95 CI%: 19.99–46.74) in women. The result showed there was statistically significant association between PI and Female sex (Pooled Est: 1.551, 95% CI: 1.199–2.006, z = 3.345, P = 0.001), diabetes (Pooled Est: 1.985, 95% CI: 1.383–2.849, z = 3.719, P = 0.000), advanced age (SMD: 0.33 years; 95% CI: 0.09–0.57), Duration of surgery (SMD: 0.47; 95% CI: 0.19–0.75) and preoperative serum albumin level (SMD: 0.56; 95% CI: 0.14–0.98). The relatively high PIs incidence among patients undergoing open heart surgery suggests that typical PI prevention methods are insufficient for this population. Targeted prevention measures must be developed and implemented.