bluuebunny/crossref_metadata_2025 huggingface dataset:
The intrinsic chaperone network of Arabidopsis stem cells confers protection against proteotoxic stress
Authors: Llamas Ernesto , Torres-Montilla Salvador , Lee Hyun Ju , Barja María Victoria , Schlimgen Elena , Dunken Nick , Wagle Prerana , Werr Wolfgang , Zuccaro Alga , Rodríguez-Concepción Manuel , Vilchez David
Published: January 2021

The biological purpose of plant stem cells is to maintain themselves while providing new pools of differentiated cells that form organs and rejuvenate or replace damaged tissues1-3. Protein homeostasis, or proteostasis, is required for cell function and viability4-7. However, the link between proteostasis and plant stem cell identity remains unknown. In contrast to their differentiated counterparts, we find that root stem cells can prevent the accumulation of aggregated proteins even under proteotoxic stress conditions such as heat stress or proteasome inhibition. Notably, root stem cells exhibit enhanced expression of distinct chaperones that maintain proteome integrity. Particularly, intrinsic high levels of the TRiC/CCT chaperonin determine stem cell maintenance and their remarkable ability to suppress protein aggregation. Overexpression of CCT8, a key activator of TRiC/CCT assembly8, is sufficient to ameliorate protein aggregation in differentiated cells and confer resistance to proteotoxic stress in plants. Taken together, our results indicate that enhanced proteostasis mechanisms in stem cells could be an important requirement for plants to persist under extreme environmental conditions and reach extreme long ages. Thus, proteostasis of stem cells could provide insights to design and breed plants tolerant to environmental challenges caused by the climate change.
Oncogenic RAS instructs morphological transformation of human epithelia via differential tissue mechanics
Authors: Nyga A. , Muñoz J. , Dercksen S. , Fornabaio G. , Uroz M. , Trepat X. , Baum B. , Matthews H. , Conte V.
Published: January 2021

The RAS proto-oncogene is a critical regulator of cell state, morphology and mechanics, and plays a key role in cancer progression. Here, by using a human epithelial model in vitro, we ask how morpho-mechanical changes driven by oncogenic RAS activation at the level of individual cells are collectively integrated to drive changes in tissue behaviour. We found that the uniform oncogenic expression of HRAS.V12 in confined epithelial monolayers causes reproducible changes in the structure and organization of the tissue, which acquires a transitory bilayered morphology. RAS-driven bilayering associates with reproducible layer-specific differences in cell-cell contractility and cell-matrix forces. These drive the initially flat tissues to form three-dimensional structures mimicking some of the behaviours seen in human cancers. Our findings establish a physical mechanism of cellular collectives through which uniform expression of RAS can be interpreted differently in different places of the same tissue to regulate its physiological and pathological morphology.
Txikispora philomaiosn. sp., n. g., a Micro-Eukaryotic Pathogen of Amphipods, Reveals Parasitism and Hidden Diversity in Class Filasterea
Authors: Urrutia Ander , Mitsi Konstantina , Foster Rachel , Ross Stuart , Carr Martin , Marigomez Ionan , Leger Michelle M. , Ruiz-Trillo Iñaki , Feist Stephen W. , Bass David
Published: January 2021

This study provides a morphological, ultrastructural, and phylogenetic characterization of a novel micro-eukaryotic parasite (2.3-2.6 µm) infecting generaEchinogammarusandOrchestia. Longitudinal studies across two years revealed that infection prevalence peaked in late April and May, reaching 64% inEchinogammarussp. and 15% inOrchestiasp., but was seldom detected during the rest of the year. The parasite infected predominantly haemolymph, connective tissue, tegument, and gonad, although hepatopancreas and nervous tissue were affected in heavier infections, eliciting melanization and granuloma formation. Cell division occurred inside walled parasitic cysts, often within host haemocytes, resulting in haemolymph congestion. Small subunit (18S) rRNA gene phylogenies including related environmental sequences placed the novel parasite as a highly divergent lineage within Class Filasterea, which together with Choanoflagellatea represent the closest protistan relatives of Metazoa. We describe the new parasite asTxikispora philomaiosn. sp. n. g., the first confirmed parasitic filasterean lineage, which otherwise comprises four free-living flagellates and a rarely observed endosymbiont of snails. Lineage-specific PCR probing of other hosts and surrounding environments only detectedT. philomaiosin the platyhelminthProcerodessp. We expand the known diversity of Filasterea by targeted searches of metagenomic datasets, resulting in 13 previously unknown lineages from environmental samples.
Antifungal activity of Propranolol againstFusariumkeratitis isolates from the Mycotic Ulcer Treatment Trial (MUTT) and the United States
Authors: Bao Ruina , Ross Brandon S. , Perez Cecilia G. , Poimenidou Galini , Prajna N. Venkatesh , Cramer Robert A. , Zegans Michael E.
Published: January 2021

SYNOPSIS

Background

Fusariumkeratitis is an infection of the cornea that often results in corneal perforation requiring corneal transplantation even with topical ocular antifungal therapy. The polyene natamycin remains the current antifungal of choice forFusariumkeratitis, but prompt sterilization of the cornea is often not achieved with contemporary therapy. Recently, natamycin synergy with the beta-adrenergic antagonist timolol againstFusariumspecies was reported.

Objective

Our objective in this study was to characterize thein vitroantifungal effects of additional beta-adrenergic antagonists alone or in combination with natamycin onFusariumkeratitis isolates from the Mycotic Ulcer Treatment Trial (MUTT) and USA.

Methods

Microbroth dilution assays were used to determine the minimal inhibitory concentration (MIC) of beta-adrenergic antagonists against 18Fusarium spp. keratitis (10 from MUTT, 8 from USA) and 3Aspergillus fumigatusisolates. The fractional inhibitory concentration index (FICI) was calculated to assess interactions with natamycin.

Results

Most beta-blockers did not show antifungal activity or synergy with natamycin with the exception of propranolol. A racemic mix of propranolol had fungicidal activity with MIC between 31 and 83 μg/mL for theFusariumisolates. The MIC of the less cardioactive R enantiomer was lower (27-83 μg/mL) than the MIC of the S enantiomer (42-104 μg/mL). The MICs of both propranolol and natamycin were lower in combination but were not synergistic. The MIC of propranolol was 156 μg/mL for theA. fumigatusisolates.

Conclusions

Propranolol has intrinsicin vitrofungicidal activity and lowers the MIC of natamycin. Both the R and S enantiomers of propranolol had antifungal activity with the MIC modestly but significantly lower for R-propranolol. These findings have relevance both for the treatment of fungal keratitis and of glaucoma in the setting of fungal keratitis. Further study of propranolol’s antifungal activity may lead to a novel treatment for fungal keratitis and possibly other fungal infections.

Trial Registration

ClinicalTrials.gov Identifier:NCT00997035(MUTT Trial)
Global analysis of cell behavior and protein localization dynamics reveals region-specific functions for Shroom3 and N-cadherin during neural tube closure
Authors: Baldwin Austin T. , Kim Juliana , Wallingford John B.
Published: January 2021

Failures of neural tube closure are common and serious birth defects, yet we have a poor understanding of the interaction of genetics and cell biology during neural tube closure. Additionally, mutations that cause neural tube defects (NTDs) tend to affect anterior or posterior regions of the neural tube but rarely both, indicating a regional specificity to NTD genetics. To better understand the regional specificity of cell behaviors during neural tube closure, we analyzed the dynamic localization of actin and N-cadherin via high-resolution tissue-level time-lapse microscopy duringXenopusneural tube closure. To investigate the regionality of gene function, we generated mosaic mutations inshroom3, a key regulator or neural tube closure This approach elucidates new differences between cell behaviors during cranial/anterior and spinal/posterior neural tube closure, provides mechanistic insight into the function ofshroom3and demonstrates the ability of tissue-level imaging and analysis to generate cell-biological mechanistic insights into neural tube closure.
Coevolutionary Analysis and Perturbation-Based Network Modeling of the SARS-CoV-2 Spike Protein Complexes with Antibodies: Binding-Induced Control of Dynamics, Allosteric Interactions and Signaling
Authors: Verkhivker Gennady M. , Di Paola Luisa
Published: January 2021

The structural and biochemical studies of the SARS-CoV-2 spike glycoproteins and complexes with highly potent antibodies have revealed multiple conformation-dependent epitopes highlighting the link between conformational plasticity of spike proteins and capacity for eliciting specific binding and broad neutralization responses. In this study, we used coevolutionary analysis, molecular simulations, and perturbation-based hierarchical network modeling of the SARS-CoV-2 S complexes with H014, S309, S2M11 and S2E12 antibodies targeting distinct epitopes to explore molecular mechanisms underlying binding-induced modulation of dynamics, stability and allosteric signaling in the spike protein trimers. The results of this study revealed key regulatory centers that can govern allosteric interactions and communications in the SARS-CoV-2 spike proteins. Through coevolutionary analysis of the SARS-CoV-2 spike proteins, we identified highly coevolving hotspots and functional clusters forming coevolutionary networks. The results revealed significant coevolutionary couplings between functional regions separated by the medium-range distances which may help to facilitate a functional cross-talk between distant allosteric regions in the SARS-CoV-2 spike complexes with antibodies. We also discovered a potential mechanism by which antibody-specific targeting of coevolutionary centers can allow for efficient modulation of allosteric interactions and signal propagation between remote functional regions. Using a hierarchical network modeling and perturbation-response scanning analysis, we demonstrated that binding of antibodies could leverage direct contacts with coevolutionary hotspots to allosterically restore and enhance couplings between spatially separated functional regions, thereby protecting the spike apparatus from membrane fusion. The results of this study also suggested that antibody binding can induce a switch from a moderately cooperative population-shift mechanism, governing structural changes of the ligand-free SARS-CoV-2 spike protein, to antibody-induced highly cooperative mechanism that can better withstand mutations in the functional regions without significant deleterious consequences for protein function. This study provides a novel insight into allosteric regulatory mechanisms of SARS-CoV-2 S proteins, showing that antibodies can modulate allosteric interactions and signaling of spike proteins, providing a plausible strategy for therapeutic intervention by targeting specific hotspots of allosteric interactions in the SARS-CoV-2 proteins.
Deep Learning Achieves Neuroradiologist-Level Performance in Detecting Hydrocephalus Requiring Treatment
Authors: Huang Yu , Moreno Raquel , Malani Rachna , Meng Alicia , Swinburne Nathaniel , Holodny Andrei I , Choi Ye , Rusinek Henry , Golomb James B , George Ajax , Parra Lucas C , Young Robert J
Published: January 2021

Purpose

In large clinical centers a small subset of patients present with hydrocephalus that requires surgical treatment. We aimed to develop a screening tool to detect such cases from the head MRI with performance comparable to neuroradiologists.

Methods

We leveraged 496 clinical MRI exams collected retrospectively at a single clinical site from patients referred for any reason. This diagnostic dataset was enriched to have 259 hydrocephalus cases. A 3D convolutional neural network was trained on 16 manually segmented exams (ten hydrocephalus) and subsequently used to automatically segment the remaining 480 exams and extract volumetric anatomical features. A linear classifier of these features was trained on 240 exams to detect cases of hydrocephalus that required treatment with surgical intervention. Performance was compared to four neuroradiologists on the remaining 240 exams. Performance was also evaluated on a separate screening dataset of 451 exams collected from a routine clinical population to predict the consensus reading from four neuroradiologists using images alone. The pipeline was also tested on an external dataset of 31 exams from a 2nd clinical site.

Results

The most discriminant features were the Magnetic Resonance Hydrocephalic Index (MRHI), ventricle volume, and the ratio between ventricle and brain volume. At matching sensitivity, the specificity of the machine and the neuroradiologists did not show significant differences for detection of hydrocephalus on either dataset (proportions test, p > 0.05). ROC performance compared favorably with the state-of-the-art (AUC 0.90–0.96), and replicated in the external validation.

Conclusion

Hydrocephalus cases requiring treatment can be detected automatically from MRI in a heterogeneous patient population based on quantitative characterization of brain anatomy with performance comparable to that of neuroradiologists.
Sahul’s megafauna were vulnerable to plant-community changes due to their position in the trophic network
Authors: Llewelyn John , Strona Giovanni , McDowell Matthew C. , Johnson Christopher N. , Peters Katharina J. , Stouffer Daniel B. , de Visser Sara N. , Saltré Frédérik , Bradshaw Corey J. A.
Published: January 2021

Extinctions stemming from environmental change often trigger trophic cascades and coextinctions. However, it remains unclear whether trophic cascades were a large contributor to the megafauna extinctions that swept across several continents in the Late Pleistocene. The pathways to megafauna extinctions are particularly unclear for Sahul (landmass comprising Australia and New Guinea), where extinctions happened earlier than on other continents. We investigated the role of bottom-up trophic cascades in Late Pleistocene Sahul by constructing pre-extinction (~ 80 ka) trophic network models of the vertebrate community of Naracoorte, south-eastern Australia. These models allowed us to predict vertebrate species’ vulnerability to cascading extinctions based on their position in the network. We tested whether the observed extinctions could be explained by bottom-up cascades, or if they should be attributed to other external causes. Species that disappeared from the community were more vulnerable, overall, to bottom-up cascades than were species that survived. The position of extinct species in the network – having few or no predators – also suggests they might have been particularly vulnerable to a new predator. These results provide quantitative evidence that trophic cascades and naivety to predators could have contributed to the megafauna extinction event in Sahul.
Genome streamlining, proteorhodopsin, and organic nitrogen metabolism in freshwater nitrifiers
Authors: Podowski Justin C. , Paver Sara F. , Newton Ryan J. , Coleman Maureen L.
Published: January 2021

Microbial nitrification is a critical process governing nitrogen availability in aquatic systems. Freshwater nitrifiers have received little attention, leaving many unanswered questions about their taxonomic distribution, functional potential, and ecological interactions. Here, we reconstructed genomes to infer the metabolism and ecology of free-living picoplanktonic nitrifiers across the Laurentian Great Lakes, a connected series of five of Earth’s largest lakes. Surprisingly, ammonia oxidizing Bacteria (AOB) related to Nitrosospira dominated over ammonia oxidizing Archaea (AOA) at nearly all stations, with distinct ecotypes prevailing in the transparent, oligotrophic upper lakes compared to Lakes Erie and Ontario. Unexpectedly, one ecotype of Nitrosospira encodes proteorhodopsin, which could enhance survival in conditions where ammonia oxidation is inhibited or substrate limited. Nitrite oxidizing Bacteria (NOB) Ca. Nitrotoga and Nitrospira fluctuated in dominance, with the latter prevailing in deeper, less productive basins. Genome reconstructions reveal highly reduced genomes and features consistent with genome streamlining, along with diverse adaptations to sunlight and oxidative stress and widespread capacity for organic nitrogen use. Our findings expand the known functional diversity of nitrifiers and establish their ecological genomics in large lake ecosystems. By elucidating links between microbial biodiversity and biogeochemical cycling, our work also informs ecosystem models of the Laurentian Great Lakes, a critical freshwater resource experiencing rapid environmental change.

Importance

Microorganisms play critical roles in Earth’s nitrogen cycle. In lakes, microorganisms called nitrifiers derive energy from reduced nitrogen compounds. In doing so, they transform nitrogen into a form that can ultimately be lost to the atmosphere by a process called denitrification, which helps mitigate nitrogen pollution from fertilizer runoff and sewage. Despite their importance, freshwater nitrifiers are virtually unexplored. To understand their diversity and function, we reconstructed genomes of freshwater nitrifiers across some of Earth’s largest freshwater lakes, the Laurentian Great Lakes. We discovered several new species of nitrifiers specialized for clear low nutrient waters, and distinct species in comparatively turbid Lake Erie. Surprisingly, one species may be able to harness light energy using a protein called proteorhodopsin, despite the fact that nitrifiers typically live in deep dark water. Our work reveals unique biodiversity of the Great Lakes and fills key gaps in our knowledge of an important microbial group, the nitrifiers.
Neisseria gonorrhoeaesubverts formin-dependent actin polymerization to colonize human macrophages
Authors: Ivanov Stanimir S. , Castore Reneau , Circu Magdalena , Dragoi Ana-Maria
Published: January 2021

Dynamic reorganization of the actin cytoskeleton dictates plasma membrane morphology and is frequently subverted by bacterial pathogens for entry and colonization of host cells. The human-adapted bacterial pathogenNeisseria gonorrhoeaecan colonize and replicate when cultured with human macrophages, however the basic understanding of how this process occurs is incomplete.N. gonorrhoeaeis the etiological agent of the sexually transmitted disease gonorrhea and tissue resident macrophages are present in the urogenital mucosa which is colonized by the bacteria. We uncovered that when gonococci colonize macrophages they can establish an intracellular or a cell surface-associated niche that support bacterial replication independently. Unlike other intracellular bacterial pathogens, which enter host cells as single bacterium, establish an intracellular niche and then replicate, gonococci invade human macrophages as a colony. Individual diplococci are rapidly phagocytosed by macrophages and transported to lysosomes for degradation. However, we found that surface-associated gonococcal colonies of various sizes can invade macrophages by triggering actin skeleton rearrangement resulting in plasma membrane invaginations that slowly engulf the colony. The resulting intracellular membrane-bound organelle supports robust bacterial replication. The gonococci-occupied vacuoles evaded fusion with the endosomal compartment and were enveloped by a network of actin filaments. We demonstrate that gonococcal colonies invade macrophages via a process mechanistically distinct from phagocytosis that is regulated by the actin nucleating factor FMNL3. Our work provides insights into the gonococci life-cycle in association with human macrophages and defines key host determinants for macrophage colonization.
Inactivated rabies virus vectored SARS-CoV-2 vaccine prevents disease in a Syrian hamster model
Authors: Kurup Drishya , Malherbe Delphine C. , Wirblich Christoph , Lambert Rachael , Ronk Adam J. , Diba Leila Zabihi , Bukreyev Alexander , Schnell Matthias J.
Published: January 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic. Although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. There is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model. CORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response. Vaccinated hamsters were protected from weight loss and viral replication in the lungs and nasal turbinates three days after challenge with SARS-CoV-2. CORAVAX also prevented lung disease, as indicated by the significant reduction in lung pathology. This study highlights CORAVAX as a safe, immunogenic, and efficacious vaccine that warrants further assessment in human trials.
Use Of Canine Olfactory Detection For COVID-19 Testing Study On U.A.E. Trained Detection Dog Sensitivity
Authors: Grandjean Dominique , Al Marzooqi Dana Humaid , Lecoq-Julien Clothilde , Muzzin Quentin , Al Hammadi Hamad Katir , Alvergnat Guillaume , Al Blooshi Kalthoom Mohammad , Al Mazrouei Salah khalifa , Alhmoudi Mohammed Saeed , Al Ahbabi Faisal Musleh , Mohammed Yasser Saifallah , Alfalasi Nasser Mohammed , Almheiri Noor Majed , Al Blooshi Sumaya Mohamed , Desquilbet Loïc
Published: January 2021

This study aimed to evaluate the sensitivity of 21 dogs belonging to different United Arab Emirates (UAE) Ministry of Interior (MOI), trained for COVID-19 olfactory detection.

The study involved 17 explosives detection dogs, two cadaver detection dogs and two dogs with no previous detection training. Training lasted two weeks before starting the validation protocol. Sequential five and seven-cone line-ups were used with axillary sweat samples from symptomatic COVID-19 individuals (SARS-CoV-2 PCR positive) and from asymptomatic COVID-19 negative individuals (SARS-CoV-2 PCR negative). A total of 1368 trials were performed during validation, including 151 positive and 110 negative samples. Each line-up had one positive sample and at least one negative sample. The dog had to mark the positive sample, randomly positioned behind one of the cones. The dog, handler and data recorder were blinded to the positive sample location.

The calculated overall sensitivities were between 71% and 79% for three dogs, between83% and 87% for three other dogs, and equal to or higher than 90% for the remaining 15 dogs (more than two thirds of the 21 dogs).

After calculating the overall sensitivity for each dog using all line-ups, “matched” sensitivities were calculated only including line-ups containing COVID-19 positive and negative samples strictly comparable on confounding factors such as diabetes, anosmia, asthma, fever, body pain, diarrhoea, sex, hospital, method of sweat collection and sampling duration. Most of the time, the sensitivities increased after matching.

Pandemic conditions in the U.A.E., associated with the desire to use dogs as an efficient mass-pretesting tool has already led to the operational deployment of the study dogs.

Future studies will focus on comparatives fields-test results including the impact of the main COVID-19 comorbidities and other respiratory tract infections.
‘Candidatus Sarmatiella mevalonica’ endosymbiont of the ciliate Paramecium provides insights on evolutionary plasticity among Rickettsiales
Authors: Castelli Michele , Lanzoni Olivia , Nardi Tiago , Lometto Stefano , Modeo Letizia , Potekhin Alexey , Sassera Davide , Petroni Giulio
Published: January 2021

Members of the bacterial order Rickettsiales are obligatorily associated with a wide range of eukaryotic hosts. Their evolutionary trajectories, in particular concerning the origin of shared or differential traits among distant sub‐lineages, are still poorly understood. Here, we characterized a novel Rickettsiales bacterium associated with the ciliate Paramecium tredecaurelia and phylogenetically related to the Rickettsia genus. Its genome encodes significant lineage‐specific features, chiefly the mevalonate pathway gene repertoire, involved in isoprenoid precursor biosynthesis. Not only this pathway has never been described in Rickettsiales, it also is very rare among bacteria, though typical in eukaryotes, thus likely representing a horizontally acquired trait. The presence of these genes could enable an efficient exploitation of host‐derived intermediates for isoprenoid synthesis. Moreover, we hypothesize the reversed reactions could have replaced canonical pathways for producing acetyl‐CoA, essential for phospholipid biosynthesis. Additionally, we detected phylogenetically unrelated mevalonate pathway genes in metagenome‐derived Rickettsiales sequences, likely indicating evolutionary convergent effects of independent horizontal gene transfer events. Accordingly, convergence, involving both gene acquisitions and losses, is highlighted as a relevant evolutionary phenomenon in Rickettsiales, possibly favoured by plasticity and comparable lifestyles, representing a potentially hidden origin of other more nuanced similarities among sub‐lineages.
Confraternal Devotions in Malta, 1670–1798
Authors: Ciappara Frans
Published: January 2021

The aims of this article are twofold. It first discusses how confraternities tried to improve the spiritual worth of their members. The brothers conducted their devotions communally in their oratory, confessing and receiving the Eucharist, hearing mass and listening to sermons. They also participated in processions while the liturgy of the suffrages for the dead was recognised as the special task of confraternities. The brethren also practised their own private devotions, like examination of conscience and the adoration of the host. Second, the brethren were not concerned solely with themselves but they influenced the other parishioners, who followed their example.
The Association of Coloproctology of Great Britain and Ireland consensus guidelines in emergency colorectal surgery
Authors: Miller Andrew S. , Boyce Kathryn , Box Benjamin , Clarke Matthew D. , Duff Sarah E. , Foley Niamh M. , Guy Richard J. , Massey Lisa H. , Ramsay George , Slade Dominic A. J. , Stephenson James A. , Tozer Phil J. , Wright Danette
Published: January 2021

Aim

There is a requirement for an expansive and up to date review of the management of emergency colorectal conditions seen in adults. The primary objective is to provide detailed evidence‐based guidelines for the target audience of general and colorectal surgeons who are responsible for an adult population and who practise in Great Britain and Ireland.

Methods

Surgeons who are elected members of the Association of Coloproctology of Great Britain and Ireland Emergency Surgery Subcommittee were invited to contribute various sections to the guidelines. They were directed to produce a pathology‐based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. Each author was asked to provide a set of recommendations which were evidence‐based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after two votes were included in the guidelines.

Results

All aspects of care (excluding abdominal trauma) for emergency colorectal conditions have been included along with 122 recommendations for management.

Conclusion

These guidelines provide an up to date and evidence‐based summary of the current surgical knowledge in the management of emergency colorectal conditions and should serve as practical text for clinicians managing colorectal conditions in the emergency setting.
Implications for the colorectal surgeon following the 100 000 Genomes Project
Authors: McDermott Frank D. , Newton Katy , Beggs Andrew D. , Clark Susan K.
Published: January 2021

Aim

The 100 000 Genomes Project was completed in 2019 with the objective of integrating genomic medicine into routine National Health Service (NHS) clinical pathways. This project and genomic research will revolutionize the way we practice colorectal surgery in the 21st century. This paper aims to provide an overview of genomic medicine and its implications for the colorectal surgeon.

Results

Within NHS England, consolidation has created seven regional Genomic Laboratory Hubs. DNA from solid tumours, including colorectal cancers, will be assessed using 500‐gene panels, results will be fed back to Genome Tumour Advisory Boards. Identifying variants from biopsies earlier in the clinical pathway may alter surgical and other treatment options for patients. However, there is an important distinction between somatic variants within a tumour biopsy and germline variants that may suggest a heritable condition such as Lynch syndrome. Novel drugs, for example immunotherapy, will increase treatment options including downstaging cancers and changing the surgical approach. The use of circulating tumour DNA (liquid biopsies) will have applications in diagnosis, treatment and surveillance of cancer. There are many exciting potential future applications of this technology for offering personalized medicine that will require multidisciplinary working and the colorectal community.

Conclusion

There are many challenges but also exciting opportunities to embed new ‘omic’ technologies and innovation into 21st century colorectal surgery. The next phase for the colorectal community is how we engage with this change, with questions around training, identification of genomic multidisciplinary team (MDT) champions and how we collaborate with the core members of the MDT, clinical geneticists and national genomic testing.
Cutaneous involvement as initial presentation of multicentric plasmacytic Castleman disease
Authors: Chen Hongxiao , Ba Wei , Chen Hao , Yang Hongyu
Published: January 2021

Castleman disease (CD) is an unusual lymphoproliferative disorder characterized by multiple lymphadenopathy accompanied by marked systemic inflammatory symptoms. CD can be unicentric (UCD) or multicentric (MCD), and it can be classified into three types based on histopathology: hyaline vascular type, plasma cell type, and mixed hyaline vascular and plasma cell type. CD involving skin is an unusual clinical manifestation. Abnormalities including rash, hyperpigmentation, cherry hemangiomatosis, paraneoplastic pemphigus, and Kaposi sarcoma have been reported to occur in MCD. Here, we reported an unusual case of MCD which presented initially with disseminated dark brown papules, patches, and plaques, and pathologically demonstrated plasma cell type CD, a finding which is rarely reported. The peculiar clinicopathological features will be discussed.
Primary epithelioid angiosarcoma of the thyroid: A case report
Authors: Bravaccini Sara , Caprara Licia , Cortecchia Stefania , De Lillo Margherita , Lega Stefania , Poli Francesca , Tasca Ignazio , Vacirca Anna , Cimatti Maria Chiara , Tumedei Maria Maddalena , Ravaioli Sara , Puccetti Maurizio
Published: January 2021

Angiosarcoma of the thyroid is a rare and aggressive primary malignant tumour of the thyroid. We report the case of a 69‐year‐old woman who presented with a red and sore skin area at the right‐anterior region of the neck. Ultrasound examination and computed tomography scan showed a non‐homogeneous mass in the right thyroid lobe. Fine needle aspiration cytology was suggestive of atypical vascular proliferation and so the patient underwent right thyroid lobectomy. The specimen measured 6 × 5 × 2.5 cm, and a reddish nodule was found, including a whitish central area of maximum 4 cm in diameter. Immunohistochemistry showed CD31 and ERG positivity, while thyroglobulin, calcitonin and TTF‐1 expression were negative, indicating a diagnosis of angiosarcoma.
Is relationship evolution good or bad? It depends! A qualitative and quantitative examination of the relational behaviors and the stimulants of supply chain integration
Authors: Verghese Anto John , Koufteros Xenophon , Schoenherr Tobias , Vanpoucke Evelyne
Published: January 2021

Buyer–supplier (B–S) relationships are dynamic. Nevertheless, research on external supply chain integration (SCI) has largely adopted a static‐snapshot perspective and has failed to grasp SCI's dynamic reality. The scant research devoted to SCI's dynamic perspectives suggests that the strength and scope of ties between buyers and suppliers differ based on integration levels. However, ambiguity persists regarding the relational behaviors exhibited across integration levels, as well as the stimulants that motivate firms to evolve their relationships. With buyers increasingly relying upon suppliers (and vice‐versa) and compounded by the knowledge that nearly half of SCI initiatives end up as failures, the need for a holistic framework that takes into account the underlying dynamics of relational behaviors and stimulants cannot be overstated. Using a mixed‐methods approach, six relational behaviors that differ in their saliency across SCI levels are identified, and eight stimulants that motivate B–S relationships to evolve are extracted. Specifically, we note that once a stimulant is activated, it remains influential across SCI levels, though its potency may vary. Our research significantly extends the contemporary understanding of SCI by (i) providing a holistic framework to comprehend SCI from a behavioral perspective, and (ii) noting that the highest integration levels do not necessarily typify successful B–S relationships. In doing so, we combine an evolutionary perspective with a relationship portfolio perspective for examining B–S relationship dynamics, thereby offering a comprehensive view to yield finer‐grained insights into B–S relationship dynamics.
Concepts and applications of ultrafast cardiac ultrasound imaging
Authors: Petrescu Aniela , D'hooge Jan , Voigt Jens‐Uwe
Published: January 2021

The concept of ultrafast echocardiographic imaging has been around for decades. However, only recent progress in ultrasound machine hardware and computer technology allowed to apply this concept to echocardiography. High frame rate echocardiography can visualize phenomena that have never been captured before. It enables a wide variety of potential new applications, including shear wave imaging, speckle tracking, ultrafast Doppler imaging, and myocardial perfusion imaging. The principles of these applications and their potential clinical use will be presented in this manuscript.
An exploration of student access to a learning management system—challenges and recommendations for educators and researchers
Authors: Chan Albert K.M. , Botelho Michael G. , Lam Otto L.T.
Published: January 2021

Introduction

This study examined student access to online resources of a faculty's learning management system (LMS). Issues relating to current e‐learning resources usage were identified and formed the basis for recommendations to help assist stakeholders in teaching, learning and research.

Methods

Learning analytics from four cohorts of undergraduate dental students were extracted from the database of a LMS spanning between 2012 and 2016. Individual datasets were combined into one master file, re‐categorised, filtered and analysed based on cohort, year of study, course and nature of online resource.

Results

A total of 157,293 access events were documented. The proportion of administrative to learning data varied across cohorts, with oldest cohort having the highest ratio (82:18) in their final year and most recent cohort having a ratio of 33:67 in their 4th year demonstrating a higher proportion to learning. SevenLearningdomains were identified in the access data: access to problem‐based learning resources was the highest and next was fixed prosthodontics videos. The prosthodontics discipline had the highest access across the curriculum while some others had very limited or even no learning access events.

Conclusion

A number of limitations have been identified with the analytics and learning resources in this LMS and engagement with learning resource provision. More detailed data capture of access use and unique identifiers to resources as well as keyword tagging of the resources are required to allow accurate mapping and support of students learning. Moreover, motivation or nudging of students behaviour to more actively engage with learning content needs exploration.
Improvement preclinical and clinical skills for dental preparations using assisted training software
Authors: Jorquera Gilbert , Sánchez Juan Pablo , Sampaio Camila S , Atria Pablo , Fernández Eduardo
Published: January 2021

Introduction

Digital workflow is currently available for different fields of dentistry. Additionally, to clinical use, digital technology is focused on the education and training of students. The objective of this study was to show the potential benefit of the use of digital CAD / CAM technology and assisted training software in the evaluation and improvement of student skills in preclinical and clinical environments.

Materials and Methods

30 models of dental preparations were digitalised and analysed by PrepCheck software, after that was used the PrepCheck Report tool, gathering the results of the analysis in an automatically created report and containing the following parameters: analysis of the conicity, distance between a preparation and the opposing jaw, analysis of the type of preparation, quality of the margin and total occlusal convergence.

Results

The use of the PrepCheck Pro 2.1 software makes evident the errors made by the students during the biomechanical preparation, since they generally change the inclination, in order to have less difficulties to comply with the parameters established in the preparations. Regarding the evaluated parameters for anterior and posterior fixed prosthesis) such as: ‘Conicity’, ‘Type of preparation’ and ‘Distance to the antagonist’, the preparations, in their majority, were classified within the tolerance range with of 50‐60%, 80‐93% and 53‐67%, respectively.

Conclusion

This pilot study demonstrated the benefits of using software and CAD/CAM technology in both preclinical and clinical environments for teaching and learning. Its use on preclinical environments allows the student observe qualitatively and quantitatively a preparation flaws when compared to a master’s preparation. Lastly, the ease of visualising errors associated with magnification would allow students to improve their skills.
Constructing a graduate career future: Working with Bourdieu to understand transitions from university to employment for students from working‐class backgrounds in England
Authors: Bathmaker Ann‐Marie
Published: January 2021

In high participation systems of higher education, the link between undergraduate study and progression to graduate employment is increasingly tenuous. One response is a growing emphasis on the development of employability skills and preparing students to take advantage of future opportunities as part of university study. This paper uses a Bourdieusian‐based conceptualisation of graduate capitals, combined with a concern for the psycho‐social dimensions of classed experience, to consider transitions through university and into employment for students from working‐class backgrounds in England, drawing on data from a study of students who attended the two universities in Bristol UK. It is argued that the assemblage of capitals that make up graduate capital could be seen as constituting a form of symbolic capital with magical powers, that hides the power relations involved in successful progression to graduate futures. While the move from university into work is more prolonged and precarious for students from all backgrounds, access to the resources that enable the development and mobilisation of graduate capitals, along with psycho‐social dimensions of class, create additional challenges for the development of viable graduate career identities for working‐class students such as those discussed in this paper. The paper concludes by noting implications for policy and practice.
Comparison of post‐operative inflammatory response in horses undergoing elective castration treated preoperatively with ceftiofur crystalline free acid or procaine penicillin G
Authors: Bergstrom T. , Frey M. , Rao S. , Bass L.
Published: January 2021

Castration is among the most common surgical procedures performed in the horse (Equus Caballus) and a variety of post‐operative complications can occur. This study aims to determine if a single dose of long‐acting ceftiofur crystalline free acid (CCFA) used as a preoperative antimicrobial in equine field castrations offers any reduction in post‐operative inflammatory markers when compared to procaine penicillin G (PPG). Sixty‐five horses aged 8 months to 2 years were randomly assigned to the CCFA (n = 33) or PPG (n = 32) treatment groups. Horses were castrated under general anaesthesia using a closed castration technique with removal of the median raphe. Quantitative and qualitative inflammatory markers were measured and short‐term complications were recorded post‐operatively on Days 3, 8 and 14. No clinically significant difference in any post‐operative inflammatory markers between the CCFA and PPG group was detected. In the CCFA group, 48% of horses experienced short‐term post‐operative complications compared to 31% in the PPG group. Regardless of the preoperative treatment, castration induced significant elevation in serum amyloid A (P<0.0001), preputial oedema (P<0.0001) and scrotal oedema (P<0.0001) at Day 3. These values returned to baseline levels by Day 8. Horses with grade 3 or above preputial oedema had elevated serum amyloid A values (P<0.001). The data from this study indicate CCFA used as a preoperative antibiotic for routine castration offers no advantages over PPG. The difference in complication rate between groups is likely of minimal clinical importance, as all complications were mild and self‐limiting.
Effects of artificial intelligence on English speaking anxiety and speaking performance: A case study
Authors: El Shazly Reham
Published: January 2021

Foreign language anxiety (FLA) has been a perennial concern in language learning, as foreign language (FL) learners often communicate feelings of anxiety, stress, or nervousness. This study explored the role of artificial intelligence (AI) applications in speaking practice for FLA management of 48 undergraduate participants in an EFL class in Egypt. An eight‐week, quasi‐experimental pretest–posttest design examined learner anxiety levels using a 33‐item FLA questionnaire. Their oral proficiency was assessed via roleplaying using an interaction‐enhanced public version of the IELTS speaking evaluation rubric. The results confirmed that FL learners experienced FLA pre‐ and post‐intervention. The identified anxiety levels played a facilitative role in FL learning with several ensuing gains. The use of conversationally enhanced AI chatbots in interactive activities slightly intensified learners' FLA, thus meriting further investigation of these objectives. Overall, subject to further development, AI chatbots are promising for significantly improving linguistic output gains; however, this study found that learners' speech‐related anxieties were not reduced following the interactions with the chatbots. It is concluded that FLA plays an underexplored facilitative role in sharpening learner cognitive faculties and linguistic capacities. Moreover, AI chatbots may be beneficial in advancing FL learning with significant potential in EFL contexts, facilitating improved interaction and oral communication. These findings support the integration of AI technologies as effective tools in FL education, providing flexible, interactive, and learner‐centred learning. This study is expected to be of considerable interest to FL educators and learners.
Cost of providing a mobile dental service for dependent older people
Authors: Spatzier Hansmartin , Stillhart Angela , Hillebrecht Anna‐Lena , McKenna Gerald , Srinivasan Murali
Published: January 2021

Background and Objective

Dental care provision in long‐term care facilities (LTCFs) is often a problem despite the high demand. LTCF residents would greatly benefit from a concept that provides an onsite dental care. A rational evaluation of the costs to render this service as well as the cost benefits is worth investigating. This study aimed to calculate the costs involved in providing a mobile dental clinic (MDC) service for LTCF residents in Zurich, Switzerland.

Materials and Methods

Cost models for setting up, executing and maintaining an MDC unit were generated. The costs included personnel, equipment/material, maintenance and running costs. The treatment costs were calculated for the treatment in MDC, university‐setting dental clinic (UC) and private practice (PP). Hypothetical cost estimates were generated for the return of the invested capital. Costs incurred for the institutions for accommodating the MDC visit were also calculated.

Results

The set‐up capital required to start a MDC in Switzerland (for 2020) was approximately around CHF 505'007.90 (Euros 466'576.80) and was around CHF 452'666.48 (Euros 418'218.56) when a dental care professional (DCP) substituted the dentist. The estimated cost savings for an LTCF resident in the MDC were CHF 205.60 (Euros 189.95) when compared to a UC and approximately CHF 226.34 (Euros 209.12) when compared to a PP. With the dentist, the return of the invested capital can be expected by 3 years while it would take around 6 years with the DCP, assuming that the maximum number of patients possible‐to‐treat are treated every year. The daily running costs for the LTCF for accommodating the MDC visit were approximately CHF 299.04 (Euros 276.28).

Conclusions

Delivery of oral health services for LTCF residents through the use of a MDC service seems to be an effective model for dependent elders with limited access to care. However, the costs of maintaining this service are high with similarly large start‐up costs. Future development of this model by utilising dental care professionals may produce cost savings but with a more limited range of services offered.
Race in South Asia: Colonialism, nationalism and modern science
Authors: Ghoshal Sayori
Published: January 2021

Unlike caste and religion, race has not been considered a primary lens for reading the formative histories of the different communities in colonial India. “Race” in South Asia holds a prominent place primarily in the history of medicine. Largely, this scholarship can be considered situated within the more generalized framework of race being the determinant of colonial difference. Beyond that, however, the significant role “race” played in producing knowledge about the difference between communities within the subcontinent, has been underexamined. In the early‐mid 20th century, despite critiquing European race science, several Indian scholars continued to use “race” as a scientific object in order to trace racial difference and affinity between various communities—particularly, Dalits, Muslims, and Adivasis. This anticolonial, nationalist science which derived from certain European methods (viz., anthropometry), without conceding to all conclusions predominant in Europe (viz., the existence of racial purity), contributed to the production of upper‐caste Hindus as the hegemonic population of India. This article argues that much insight remains to be gained by focusing on how race played a fundamental role in producing the notion of the upper caste Hindu population as hegemonic, in distinction to its others, like Scheduled Castes and Muslims.