bluuebunny/crossref_metadata_2025 huggingface dataset:
Two novel loci underlie natural differences inCaenorhabditis elegansmacrocyclic lactone responses
Authors: Evans Kathryn S. , Wit Janneke , Stevens Lewis , Hahnel Steffen R. , Rodriguez Briana , Park Grace , Zamanian Mostafa , Brady Shannon C. , Chao Ellen , Introcaso Katherine , Tanny Robyn E. , Andersen Erik C.
Published: January 2021

Parasitic nematodes cause a massive worldwide burden on human health along with a loss of livestock and agriculture productivity. Anthelmintics have been widely successful in treating parasitic nematodes. However, resistance is increasing, and little is known about the molecular and genetic causes of resistance. The free-living roundwormCaenorhabditis elegansprovides a tractable model to identify genes that underlie resistance. Unlike parasitic nematodes,C. elegansis easy to maintain in the laboratory, has a complete and well annotated genome, and has many genetic tools. Using a combination of wild isolates and a panel of recombinant inbred lines constructed from crosses of two genetically and phenotypically divergent strains, we identified three genomic regions on chromosome V that underlie natural differences in response to the macrocyclic lactone (ML) abamectin. One locus was identified previously and encodes an alpha subunit of a glutamate-gated chloride channel (glc-1). Here, we validate and narrow two novel loci using near-isogenic lines. Additionally, we generate a list of prioritized candidate genes identified inC. elegansand in the parasiteHaemonchus contortusby comparison of ML resistance loci. These genes could represent previously unidentified resistance genes shared across nematode species and should be evaluated in the future. Our work highlights the advantages of usingC. elegansas a model to better understand ML resistance in parasitic nematodes.

Author Summary

Parasitic nematodes infect plants, animals, and humans, causing major health and economic burdens worldwide. Parasitic nematode infections are generally treated efficiently with a class of drugs named anthelmintics. However, resistance to many of these anthelmintic drugs, including macrocyclic lactones (MLs), is rampant and increasing. Therefore, it is essential that we understand how these drugs act against parasitic nematodes and, conversely, how nematodes gain resistance in order to better treat these infections in the future. Here, we used the non-parasitic nematodeCaenorhabditis elegansas a model organism to study ML resistance. We leveraged natural genetic variation between strains ofC. eleganswith differential responses to abamectin to identify three genomic regions on chromosome V, each containing one or more genes that contribute to ML resistance. Two of these loci have not been previously discovered and likely represent novel resistance mechanisms. We also compared the genes in these two novel loci to the genes found within genomic regions linked to ML resistance in the parasiteHaemonchus contortusand found several cases of overlap between the two species. Overall, this study highlights the advantages of usingC. elegansto understand anthelmintic resistance in parasitic nematodes.
Novel Thyroid-Specific Autoantibodies in Patients with Immune-Related Adverse Events Involving the Thyroid Gland
Authors: Yamauchi Ichiro , Yasoda Akihiro , Hakata Takuro , Yamashita Takafumi , Hirota Keisho , Ueda Yohei , Fujii Toshihito , Taura Daisuke , Sone Masakatsu , Inagaki Nobuya
Published: January 2021

Aims

Programmed cell death-1 (PD-1) blockade therapy frequently results in immune-related adverse events involving the thyroid gland (thyroid irAEs). Although clinical features of thyroid irAEs are known, the mechanisms remain unclear. Here, we conducted a pilot study to investigate mechanisms of thyroid irAE development from the perspective of autoantibodies.

Methods

We performed immunoprecipitation-based assays using sera of 3 patients who developed thyroid irAEs with PD-1 blockade therapy by nivolumab and HEK293T cell lysates, including overexpressed proteins of interest (NKX2-1, PAX8, FOXE1, and HHEX; thyroid-specific transcriptional factors). The pellets were analyzed by western blot to detect the HiBit tag attached to the C-terminus of the proteins.

Results

Relevant changes to NKX2-1 bands were not seen in all 3 patients, but PAX8 bands were augmented in patient 2 with lung cancer and patient 3 with renal cell carcinoma. In addition, FOXE1 bands were augmented in patient 1 with malignant melanoma and patient 3, and a HHEX band was augmented in patient 3. Thus, we revealed novel thyroid-specific autoantibodies, PAX8Ab, FOXE1Ab, and HHEXAb. Expression patterns of the antigens recognized by these antibodies were not identical to the primary sites, so autoimmune responses in thyroid irAE may originate from the thyroid gland, and not the malignancy. Considering that TPOAb rather than TgAb is often negative in patients with thyroid irAEs, other mechanisms such as cytotoxic T cell and antigenicity of thyroglobulin may be involved.

Conclusions

Although the significance of these novel autoantibodies needs further examination, the present study provides new insights for thyroid autoimmunity.
An enhancer sequence in the intrinsically disordered region of the essential cell division protein FtsZ promotes conformation-guided substrate processing by ClpXP inEscherichia coli
Authors: Viola Marissa G. , Perdikari Theodora Myrto , Trebino Catherine , Rahmani Negar , Mathews Kaylee L. , Pena Carolina Meija , Chua Xien Yu , Xuan Botai , LaBreck Christopher J. , Fawzi Nicolas L. , Camberg Jodi L.
Published: January 2021

The essential bacterial division protein inEscherichia coli, FtsZ, assembles into the FtsZ-ring at midcell and recruits other proteins to the division site to promote septation. A region of the FtsZ amino acid sequence that links the conserved polymerization domain to a C-terminal protein interaction site was predicted to be intrinsically disordered and has been implicated in modulating spacing and architectural arrangements of FtsZ filaments. While the majority of cell division proteins that directly bind to FtsZ engage either the polymerization domain or the C-terminal interaction site, ClpX, the recognition and unfolding component of the bacterial ClpXP proteasome, has a secondary interaction with the predicted intrinsically disordered region (IDR) of FtsZ when FtsZ is polymerized. Here, we use NMR spectroscopy and reconstituted degradation reactions in vitro to demonstrate that this linker region is indeed disordered in solution and, further, that amino acids in the IDR of FtsZ enhance the degradation by conformationally-guided interactions.
Dissociable developmental trajectories of Orbitofrontal subregion grey matter volume
Authors: Gibbons S. G. , Noonan M. P.
Published: January 2021

Adolescence is a period of development which is characterised by distinct differences in decision-making strategies relative to adults. While it is broadly established that there are relative differences in the structural maturation of the prefrontal cortex (PFC) and subcortical reward nuclei, such as the amygdala and ventral striatum, heterogeneitywithinthe PFC is often neglected. In particular very little is known about the fine-scale gray matter (GM) development of the Orbitofrontal Cortex (OFC), itself critical to a number of learning and decision-making mechanisms which show delayed development trajectories. Here we applied voxel-based morphometry to examine subregional differences in OFC grey matter in high-quality structural MRI scans of 125 subjects aged 11-35yrs from the Human Connectome Project. First, we examined fine-scale GM maturation in 5 anatomically dissociable OFC subregions and identified the best-fitting polynomial model. Next, we directly compared developmental trajectories across 3 functionally dissociable subregions, revealing a complex topological developmental profile from medial to lateral subregions. Collectively, the two complementary analyses suggest that while unequivocally the phylogenetically younger lateral OFCs showed the greatest shift in GM volume across adolescence, with maturation continuing well into young adulthood, the differences between the medial and central OFC subregions suggested a more complex pattern of maturation than a simple graded medial to lateral topological development. We argue that knowledge of these fine-scale anatomical differences in maturation could explain precise mechanistic differences in goal-directed behaviours.
Ethnic differences in the incidence of clinically diagnosed influenza: an England population-based cohort study 2008-2018
Authors: Davidson Jennifer A. , Banerjee Amitava , Mathur Rohini , Ramsay Mary , Smeeth Liam , Walker Jemma , McDonald Helen , Warren-Gash Charlotte
Published: January 2021

We used primary and linked secondary healthcare data to investigate the incidence of clinically diagnosed influenza/influenza-like-illness (ILI) by ethnicity in England from 2008-2018. We identified higher incidence rate ratios for influenza/ILI among South Asian (1.70, 95% CI 1.66-1.75), Black (1.48, 1.44-1.53) and Mixed (1.22, 1.15-1.30) groups compared to White ethnicity.

People from ethnic minority backgrounds are represented disproportionately among patients with severe COVID-19. Recent research has found people of Black and South Asian ethnicity have increased risk of SARS-CoV-2 infection, COVID-19-related hospitalization and death, independent of deprivation, occupation, household size, and underlying health conditions(1,2).

The COVID-19 pandemic has reinforced the importance of seasonal influenza vaccination. By preventing influenza-related hospitalization, vaccination can minimize the risk of hospital-acquired COVID-19 (co-) infection for these individuals and reduce health service pressures, particularly the need for isolation of patients with respiratory symptoms awaiting COVID-19 test results.

In the UK, influenza vaccine is routinely recommended for adults aged ≥65 years, or people <65 years with underlying health conditions. These recommendations formed the basis of the original guidance to identify patients at moderate- and high-risk of COVID-19. Influenza vaccine recommendations were expanded for the 2020/21 season to include all adults ≥50 years(3). However, vaccine uptake among clinical risk groups is low, particularly for Black and Mixed Black ethnic groups(4). In addition, people of non-White ethnicity have higher risk of severe outcomes following influenza infection(5,6). It is unclear whether this is driven by the risk of infection or complications, with most research focused on distal outcomes rather than initial infection risk.

Here we investigate the incidence of influenza and influenza-like-illness (ILI) by ethnicity from 2008-2018 among people not eligible for routine influenza vaccination, to consider disparities in infection risk.
Putting assemblage to work to explore pedagogical practices in health education in Aotearoa New Zealand
Authors: Dixon Rachael , Abel Gillian , Burrows Lisette
Published: January 2021

Purpose

In Aotearoa New Zealand, Health Education is socio-critical in orientation and is offered as a subject that can offer credits towards the national secondary school qualification. The purpose of this paper is to explore the learning experiences of people who studied Health Education to the final level of secondary schooling in Aotearoa New Zealand. The authors focus specifically on how the subject is taught; or the pedagogical practices that are “put to work” in the Health Education learning environment.

Design/methodology/approach

Using in-depth interviews as the authors’ method of data production, they experiment with a post-qualitative approach to analysis while traversing the theoretical terrain of new materialism. In doing so, they explicate the non-human and human elements that are arranged in a pedagogical assemblage – and explore what these elements can do.

Findings

The authors found that an array of pedagogical practices were put to work in the senior secondary school Health Education classroom: Student-centred approaches, a non-judgemental and energetic tone to teaching, deployment of human and non-human resources, and students connecting with the community. The authors argue that these practices open up possibilities for a critical Health Education.

Practical implications

This research addresses an empirical gap in the literature by focusing on Health Education in the senior secondary levels of schooling. The findings in this paper may provide readers who are Health Education teachers with ideas that could be of material use to them in their teaching practice. In terms of implications for researchers, the authors demonstrate how putting “new” theory and methodological approaches to work in the area of school-based Health Education can produce novel ways of thinking about the subject and what it can do.

Originality/value

The shifting nature of the pedagogical assemblage can ignite new ways of thinking about teaching practice in the Health Education classroom and the capacities that result for learners. In combination with a post-qualitative approach to analysis, the paper provides a novel approach to exploring Health Education.
Putative resistance and tolerance mechanisms have little impact on disease progression for an emerging salamander pathogen
Authors: Wilber Mark Q. , Carter Edward Davis , Gray Matthew J. , Briggs Cheryl J.
Published: January 2021

Resistance and tolerance are unique host defence strategies that can limit the impacts of a pathogen on a host. However, for most wildlife–pathogen systems, there are still fundamental uncertainties regarding (a) how changes in resistance and tolerance can affect disease outcomes and (b) the mechanisms underlying resistance and tolerance in host populations.

Here, we first compared observed patterns of resistance and tolerance and their effects on disease outcomes among salamander species that are susceptible to infection and mortality from the emerging fungal pathogen Batrachochytrium salamandrivorans (Bsal). We then tested whether two putative mechanisms that contribute to host resistance and tolerance, skin sloughing and skin lesion reduction, predicted reduced Bsal growth rate or increased host survival during infection, respectively.

We performed multi‐dose Bsal challenge experiments on four species of Salamandridae found throughout North America. We combined the laboratory experiments with dynamic models and sensitivity analysis to examine how changes in load‐dependent resistance and tolerance functions affected Bsal‐induced mortality risk. Finally, we used our disease model to test whether skin sloughing and lesion reduction predicted variability in infection outcomes not described by Bsal infection intensity.

We found that resistance and tolerance differed significantly among salamander species, with the most susceptible species being both less resistance and less tolerant of Bsal infection. Our dynamic model showed that the relative influence of resistance versus tolerance on host survival was species‐dependent—increasing resistance was only more influential than increasing tolerance for the least tolerant species where changes in pathogen load had a threshold‐like effect on host survival. Testing two candidate mechanisms of resistance and tolerance, skin sloughing and lesion reduction, respectively, we found limited support that either of these processes were strong mechanisms of host defence.

Our study contributes to a broader understanding of resistance and tolerance in host–pathogen systems by showing that differences in host tolerance can significantly affect whether changes in resistance or tolerance have larger effects on disease outcomes, highlighting the need for species and even population‐specific management approaches that target host defence strategies.

A free Plain Language Summary can be found within the Supporting Information of this article.
Species asynchrony stabilises productivity under extreme drought across Northern China grasslands
Authors: Muraina Taofeek O. , Xu Chong , Yu Qiang , Yang Yadong , Jing Minghui , Jia Xiaotong , Jaman Md. Shahariar , Dam Quockhanh , Knapp Alan K. , Collins Scott L. , Luo Yiqi , Luo Wentao , Zuo Xiaoan , Xin Xiaoping , Han Xingguo , Smith Melinda D.
Published: January 2021

Biodiversity can stabilise productivity through different mechanisms, such as asynchronous species responses to environmental variability and species stability. Global changes, like intensified drought, could negatively affect species richness, species asynchrony and species stability, but it is unclear how changes in these mechanisms will affect the stability of above‐ground primary productivity (ANPP) across ecosystems.

We studied the effects of a 4‐year extreme drought on ANPP stability and the underlying mechanisms (species richness, species asynchrony and species stability) across six grasslands in Northern China. We also assessed the relative importance of these mechanisms in determining ANPP stability under extreme drought.

We found that extreme drought decreased ANPP stability, species richness, species asynchrony and species stability across the six grasslands. However, structural equation modelling revealed that species asynchrony, not species richness or species stability, was the most important mechanism promoting stability of ANPP, regardless of drought across the six grasslands.

Synthesis. Our results suggest that species asynchrony, not species richness and species stability, consistently buffers ecosystem stability against extreme drought across and within grasslands spanning a broad precipitation gradient. Thus, species asynchrony may be a more general mechanism for promoting stability of ANPP in grasslands in the face of intensified drought.
Size‐selective exclusion of mammals and invertebrates differently affects grassland plant communities depending on vegetation type
Authors: Wang Xiaowei , Schütz Martin , Risch Anita C.
Published: January 2021

Human‐caused loss of vertebrate and invertebrate animals, defaunation, is increasing, and potentially affects plant community structure of diverse grassland ecosystems world‐wide.

We experimentally simulated defaunation using size‐selective fences to progressively exclude large‐, medium‐ and small‐sized mammals, and invertebrates from two subalpine vegetation types in the Swiss National Park (SNP): intensively grazed short‐grass and moderately grazed tall‐grass vegetation. We assessed plant community properties yearly from 2009 to 2013, and examined treatment effects on plant community structure in the two grassland types.

In the short‐grass vegetation, the exclusion of large mammals increased total plant biomass, while the exclusion of large and medium‐sized mammals increased total, grass and forb biomass compared to when all animals had access. These increases became stronger when invertebrates were also excluded. The exclusion of all mammals and invertebrates increased biomass of grasses by 205%, forbs by 100% and total plant biomass by 118% compared to when all animals had access, hence enhancing relative biomass of grasses from 43.6% to 60%, changing plant species composition and lowering richness of forbs by 16%, the number of plant families by 13% and family‐level Shannon diversity by 23%. In contrast to these significant community‐level responses found in the short‐grass vegetation, there was no evidence that the size‐selective exclusion of animals altered the plant community structure of the tall‐grass vegetation. The contrasting results were due to the difference in plant community composition prior to our experiment, which were related to differences in quantity and quality of forage and in grazing intensities of herbivores between the two grassland types.

Synthesis. Our results showed that different‐sized animals, in particular large mammals and invertebrates, contributed to maintain the plant community structure in the short‐grass vegetation, highlighting the importance of multiple, functionally different animal groups for ecosystem functioning and stability. In contrast to the short‐grass vegetation, we could not detect such a top‐down control by animals in the tall‐grass vegetation. Our results suggest that potential defaunation effects on grassland plant community structure depend on the degree of grazing pressure release and grassland vegetation type.
Bilberry seed production explains spatiotemporal synchronicity in bank vole population fluctuations in Norway
Authors: Selås Vidar , Framstad Erik , Rolstad Jørund , Sonerud Geir A. , Spidsø Tor K. , Wegge Per
Published: January 2021

Population fluctuations of small rodents are often synchronized over larger areas (>100 km) than what could be explained by dispersal, suggesting that the synchronizing factor is weather‐related and possibly mediated through changes in food quality. Because bank vole (Myodes glareolus) populations usually peak 1 year after peaks in reproduction of the staple winter food plant bilberry (Vaccinium myrtillus), we tested for a possible link between food and spatial synchrony by comparing the synchrony in bank vole population indices and bilberry seed production indices between three study areas across about 20,000 km2 in South Norway during a four decade period (1979–2019). There were subperiods of spatial synchrony and asynchrony between the study areas in the fluctuations of bank vole numbers and bilberry seed production, with the latter part of the study period displaying more pronounced synchrony than the first and middle part. However, with a few marked exceptions, when vole fluctuations were spatially out of phase across study areas so was bilberry seed production. Thus, we conclude that bilberry seed production to a large extent explained the spatiotemporal synchronicity in bank vole population fluctuations. Although bilberry seed production seems to be a causal driver of vole fluctuations, it remains to be seen to what extent the chemical composition of bilberry plants influences vole performance. Finally, certain weather factors may still influence voles directly, or indirectly by triggering bilberry seed production.
Un‐nudgeable Nudgers: An Experiment on Voluntary Contribution to an Academic Network Working on the CAP. A Note
Authors: Lefebvre Marianne , Barreiro‐Hurlé Jesus , Rommel Jens
Published: January 2021

Peer networks can positively affect individual careers and the scientific enterprise as a whole. People’s willingness to contribute to such networks is poorly understood. In an email experiment, we investigated how framing the future research environment affects people’s willingness to contribute to an emerging academic network. In spite of relatively large treatment effects, we do not find statistically significant effects of pessimistic or optimistic messaging on the willingness to contribute. We discuss limitations of the small sample size and the future research potential of network nudges.
RNA interference‐mediated silencing of vATPase subunits A and E affect survival and development of the 28‐spotted ladybeetle, Henosepilachna vigintioctopunctata
Authors: Guo Wei , Guo Mujuan , Yang Chunxiao , Liu Zhuoqi , Chen Shimin , Lü Jing , Qiu Baoli , Zhang Youjun , Zhou Xuguo , Pan Huipeng
Published: January 2021

RNA interference (RNAi) has emerged as a powerful tool for developing novel management strategies for controlling insect pests. The 28‐spotted ladybeetle, Henosepilachna vigintioctopunctata is one of the most important pests attacking solanaceous plants in Asia. In this study, the potential of dietary RNAi to manage H. vigintioctopunctata was investigated using both in vitro synthesized and bacterially expressed double‐stranded RNAs (dsRNAs) of HvvATPase A and HvvATPase E. The expression levels of HvvATPase A and HvvATPase E were higher in Malpighian tubules than in other tissue types. The silencing of HvvATPase A and HvvATPase E led to significant mortality in H. vigintioctopunctata larvae. In addition, the ingestion of HvvATPase A and HvvATPase E significantly deterred feeding behavior and subsequently arrested the development of H. vigintioctopunctata. Notably, the bacterially expressed dsRNAs consistently caused higher mortality in larvae and adults. Finally, the nontarget effects of the dsRNAs of H. vigintioctopunctata on the predatory ladybeetle Propylaea japonica were evaluated. P. japonica 1st instar larvae were administered vATPase A and vATPase E dsRNAs from H. vigintioctopunctata and P. japonica under the worst‐case scenario, in which dsGFP served as negative control. There were significant effects of dsHvvATPase A on P. japonica at the transcriptional level but not at the organismal level, whereas dsHvvATPase E did not effect P. japonica at either the transcriptional or the organismal level. Collectively, the results of the study suggest that HvvATPase A and HvvATPase E can act as novel molecular targets for the control of H. vigintioctopunctata.
Enzymatic hydrolysis of black cricket (Gryllus assimilis) proteins positively affects their antioxidant properties
Authors: de Matos Francielle Miranda , Novelli Paula Kern , de Castro Ruann Janser Soares
Published: January 2021

The development of innovative ingredients through biotechnological routes has established insect proteins as an emerging source of bioactive peptides. The current study aimed to evaluate the antioxidant properties of black cricket (Gryllus assimilis) protein hydrolysates produced using the proteases FlavourzymeTM 500L, AlcalaseTM 2.4L, and NeutraseTM 0.8L, either individually or in binary/ternary combinations. The enzymatic hydrolysis promoted an increase of approximately 160% in total antioxidant capacity and 93% in the ferric reducing antioxidant power. The isolated use of the enzyme FlavourzymeTM 500L showed the most prominent positive effect on the antioxidant properties, presenting an IC50 value of 455 and 71 µg/mL for DPPH and ABTS radicals scavenging activities, respectively. This sample was composed mainly of small peptides (MW < 3 kDa), in which the antioxidant properties increased after fractionation by ultrafiltration. Gel electrophoresis analysis showed protein hydrolysates composed mainly of polypeptide chains with a mass of less than 14 kDa. Finally, the enzymatic treatment proved to be an efficient process to improve the antioxidant properties of black cricket proteins, increasing the possibility of applying these hydrolysates as bioactive ingredients in food or nutraceutical products.

Practical Application

Insects represent an alternative source of proteins. Their modification through hydrolysis allows for the acquisition of compounds with great potential in industrial applications, such as functional ingredients or for nutraceutical purposes. The use of our experimental design proved to be an adequate tool for defining the best process conditions required for increasing the attainment of biologically active compounds.
A high‐quality genome assembly of the eggplant provides insights into the molecular basis of disease resistance and chlorogenic acid synthesis
Authors: Li Dandan , Qian Jun , Li Weiliu , Yu Ning , Gan Guiyun , Jiang Yaqin , Li Wenjia , Liang Xuyu , Chen Riyuan , Mo Yongcheng , Lian Jinmin , Niu Yongchao , Wang Yikui
Published: January 2021

The eggplant (Solanum melongena L.) is one of the most important Solanaceae crops, ranking third for total production and economic value in its genus. Herein, we report a high‐quality, chromosome‐scale eggplant reference genome sequence of 1155.8 Mb, with an N50 of 93.9 Mb, which was assembled by combining PacBio long reads and Hi‐C sequencing data. Repetitive sequences occupied 70.1% of the assembly length, and 35,018 high‐confidence protein‐coding genes were annotated based on multiple sources. Comparative analysis revealed 646 species‐specific families and 364 positive selection genes, conferring distinguishing traits on the eggplant. We performed genome‐wide comparative identification of disease resistance genes and discovered an expanded gene family of bacterial spot resistance in eggplant and pepper, but not in tomato and potato. The genes involved in chlorogenic acid synthesis were comprehensively characterized. Highly similar chromosomal distribution patterns of polyphenol oxidase genes were observed in the eggplant, tomato, and potato genomes. The eggplant reference genome sequence will not only facilitate evolutionary studies of the Solanaceae but also facilitate their breeding and improvement.
Teaching Global Citizenship: The Global Leadership Initiative, its Impact and Challenges
Authors: Dobson Hugo , Bishop Matthew L. , Enns Charis , Horn Philipp , Stiles Gregory
Published: January 2021

In 2015, as part of the University of Sheffield's strategic commitment to innovation in its approaches to internationalization, as well as recognition of both the importance of student employability and growing opportunities in student‐led research, the Faculty of Social Sciences established a unique learning and research initiative in the shape of the Global Leadership Initiative as part of the Global Learning Opportunities in the Social Sciences programme. Its mission reflects both a desire to develop Social Sciences students as global citizens with an international outlook and a belief that staff and students can, and should, collaborate as partners in research. To this end, these initiatives have provided students, who would not normally have the opportunity, with the means to blend an international experience into their studies and understand the Social Sciences in this context. At the same time, they have sought to provide students in the Faculty with a unique Social Sciences research‐based opportunity that will enhance their employability. This article outlines the development of these Global Citizenship Education initiatives before exploring the pedagogical benefits and challenges of the programme from an academic and student perspective based on semi‐structured interviews, surveys and student evaluations.
Early‐onset interstitial pneumonitis in a patient with advanced non‐small cell lung cancer treated with crizotinib and osimertinib
Authors: Cheng Yuan , Yu Qing , Xiong Yan , Guo Cuiyan , Nie Ligong
Published: January 2021

Both crizotinib and osimertinib have been reported to have an adverse effect of interstitial pneumonitis in the treatment of non‐small cell lung cancer (NSCLC). Here, we report the case of a 60‐year‐old male patient with advanced NSCLC resistant to osimertinib. Crizotinib was administered in combination with osimertinib due to elevated mesenchymal epithelial transition (MET) copy number amplification. However, early‐onset interstitial pneumonitis occurred within two days.
Mtor inhibition by INK128 extends functions of the ovary reconstituted from germline stem cells in aging and premature aging mice
Authors: Heng Dai , Sheng Xiaoyan , Tian Chenglei , Li Jie , Liu Linlin , Gou Mo , Liu Lin
Published: January 2021

Stem cell transplantation has been generally considered as promising therapeutics in preserving or recovering functions of lost, damaged, or aging tissues. Transplantation of primordial germ cells (PGCs) or oogonia stem cells (OSCs) can reconstitute ovarian functions that yet sustain for only short period of time, limiting potential application of stem cells in preservation of fertility and endocrine function. Here, we show that mTOR inhibition by INK128 extends the follicular and endocrine functions of the reconstituted ovaries in aging and premature aging mice following transplantation of PGCs/OSCs. Follicular development and endocrine functions of the reconstituted ovaries by transplanting PGCs into kidney capsule of the recipient mice were maintained by INK128 treatment for more than 12 weeks, in contrast to the controls for only about 4 weeks without receiving the mTOR inhibitors. Comparatively, rapamycin also can prolong the ovarian functions but for limited time. Furthermore, our data reveal that INK128 promotes mitochondrial function in addition to its known function in suppression of immune response and inflammation. Taken together, germline stem cell transplantation in combination with mTOR inhibition by INK128 improves and extends the reconstituted ovarian and endocrine functions in reproductive aging and premature aging mice.
Comparative morphometrical studies on the skull bones of barking deer (Muntiacus muntjak) and sambar deer (Rusa unicolor)
Authors: Keneisenuo Keneisenuo , Choudhary Om Prakash , Kalita Pranab Chandra , Choudhary Priyanka , Kalita Arup , Doley Probal Jyoti , Chaudhary Jitendra Kumar
Published: January 2021

The present study reports data on the skull bone morphometry of barking and sambar deer. The skulls of adult barking deer (n = 6) and sambar deer (n = 6) of either sex (n = 3 males and n = 3 females) were collected from the Aizawl Zoological Park, Aizawl, Mizoram, India, with official permission from the Government of Mizoram. Anatomically, barking and sambar deer's skulls were elongated, pyramid‐like, dolichocephalic and consisted of thirty‐two cranial and facial bones. The cranial bones were eleven (three single and four paired), comprising of occipital, sphenoid, ethmoid, frontal, interparietal, parietal and temporal. The facial bones were twenty‐one (one single and ten were paired), consisting of the maxilla, premaxilla (incisive), palatine, pterygoid, nasal, lacrimal, zygomatic (malar), vomer, turbinates, mandible and hyoid. In the present study, altogether 41 different measurements were taken morphologically and 6 different indices were applied. The obtained morphometrical parameters were significantly (p < .01, p < .05) higher in males than females of both species. Species wise, all obtained parameters were higher in sambar deer than barking deer. The obtained 41 different skull parameters and 6 indices showed statistically significant differences (p < .01 and p < .05) between both sexes of barking and sambar deer; however, practically these differences were meagre. The present morphometrical study on the skull of both species can help the wildlife professionals and zoo veterinarians determine the sex of these animals and differentiate it from other domestic and wild small ruminants for solving veterolegal cases. This study's findings will also motivate and assist other comparative studies with various domestic and wild small ruminants.
Fundamentals and innovations in regional anaesthesia for infants and children
Authors: Heydinger G. , Tobias J. , Veneziano G.
Published: January 2021

Regional anaesthesia in children has evolved rapidly in the last decade. Although it previously consisted of primarily neuraxial techniques, the practice now incorporates advanced peripheral nerve blocks, which were only recently described in adults. These novel blocks provide new avenues for providing opioid‐sparing analgesia while minimising invasiveness, and perhaps risk, associated with older techniques. At the same time, established methods, such as infant spinal anaesthesia, under‐utilised in the last 20 years, are experiencing a revival. The impetus has been the concern regarding the potential long‐term neurocognitive effects of general anaesthesia in the young child. These techniques have expanded from single shot spinal anaesthesia to combined spinal/epidural techniques, which can now effectively provide surgical anaesthesia for procedures below the umbilicus for a prolonged period of time, thereby avoiding the need for general anaesthesia. Continuous 2‐chloroprocaine infusions, previously only described for intra‐operative regional anaesthesia, have gained popularity as a means of providing prolonged postoperative analgesia in epidural and continuous nerve block techniques. The rapid, liver‐independent metabolism of 2‐chloroprocaine makes it ideal for prolonged local anaesthetic infusions in neonates and small infants, obviating the increased risk of local anaesthetic systemic toxicity that occurs with amide local anaesthetics. Debate continues over certain practices in paediatric regional anaesthesia. While the rarity of complications makes comparative analyses difficult, data from large prospective registries indicate that providing regional anaesthesia to children while under general anaesthesia appears to be at least as safe as in the sedated or awake patient. In addition, the estimated frequency of serious adverse events demonstrates that regional blocks in children under general anaesthesia are no less safe than in awake adults. In infants, the techniques of direct thoracic epidural placement or caudal placement with cephalad threading each have distinct advantages and disadvantages. As the data cannot support the safety of one technique over the other, the site of epidural insertion remains largely a matter of anaesthetist discretion.
Volatile anaesthesia and peri‐operative outcomes related to cancer: a feasibility and pilot study for a large randomised control trial
Authors: Dubowitz J. A. , Cata J. P. , De Silva A. P. , Braat S. , Shan D. , Yee K. , Hollande F. , Martin O. , Sloan E. K. , Riedel B. ,   the Global Onco‐Anaesthesia Research Collaboration Group
Published: January 2021

Published data suggest that the type of general anaesthesia used during surgical resection for cancer may impact on patient long‐term outcome. However, robust prospective clinical evidence is essential to guide a change in clinical practice. We explored the feasibility of conducting a randomised controlled trial to investigate the impact of total intravenous anaesthesia with propofol vs. inhalational volatile anaesthesia on postoperative outcomes of patients undergoing major cancer surgery. We undertook a randomised, double‐blind feasibility and pilot study of propofol total intravenous anaesthesia or volatile‐based maintenance anaesthesia during cancer resection surgery at three tertiary hospitals in Australia and the USA. Patients were randomly allocated to receive propofol total intravenous anaesthesia or volatile‐based maintenance anaesthesia. Primary outcomes for this study were successful recruitment to the study and successful delivery of the assigned anaesthetic treatment as per randomisation arm. Of the 217 eligible patients approached, 146 were recruited, a recruitment rate of 67.3% (95%CI 60.6–73.5%). One hundred and forty‐five patients adhered to the randomised treatment arm, 99.3% (95%CI 96.2–100%). Intra‐operative patient characteristics and postoperative complications were comparable between the two intervention groups. This feasibility and pilot study supports the viability of the protocol for a large, randomised controlled trial to investigate the effect of anaesthesia technique on postoperative cancer outcomes. The volatile anaesthesia and peri‐operative outcomes related to cancer (VAPOR‐C) study that is planned to follow this feasibility study is an international, multicentre trial with the aim of providing evidence‐based guidelines for the anaesthetic management of patients undergoing major cancer surgery.
The impact of five years storage/biobanking at −80°C on mouse spermatozoa fertility, physiology, and function
Authors: Raspa Marcello , Putti Sabrina , Paoletti Renata , Barboni Barbara , Ramal‐Sanchez Marina , Lanuti Paola , Marchisio Marco , D’Atri Mario , Ortolani Claudio , Papa Stefano , Valbonetti Luca , Bernabo Nicola , Scavizzi Ferdinando
Published: January 2021

Background

We previously demonstrated how mouse spermatozoa can be efficiently stored for two years in a −80°C freezer, maintaining their ability to fertilize mouse eggs.

Objectives

The main objective here was to evaluate the effects of five years at −80°C compared to liquid nitrogen storage (LN2, control condition) on mouse sperm viability, physiological parameters, and fertilization capacity.

Materials and methods

Three different strains were used: C57BL/6N, C57BL/6J and CD1. Flow cytometry experiments were performed to analyze sperm viability (SYBR‐14 + Propidium Iodide +Hoechst33342), the intracellular calcium concentration (Fluo 3‐AM), the membrane lipid disorder (Merocyanine 540), and the mitochondrial activity (MitoTracker Red) in live spermatozoa. The in vitro fertilization (IVF) was used to evaluate the sperm fertilizing ability.

Results

Flow cytometry analysis showed that the percentage of live cells are reduced in B6N and B6J, but not in CD1 mice. However, in the live population no differences in terms of intracellular calcium concentration, membrane lipid disorder, and mitochondrial activity were reported when comparing both biobanking methods. Spermatozoa stored at −80°C for 5 years successfully fertilized the eggs and developed mouse embryo normally both in culture and in vivo, generating live pups with no differences compared to control samples stored in LN2.

Discussion

Long‐term mouse sperm storage at −80°C (five years) could be considered an ideal alternative to the most common LN2 approach, giving economical and logistic advantages. Moreover, the precise information originated from the flow cytometry analysis stands up this technique as an optimal strategy to evaluate the sperm quality and ranking.

Conclusion

It is demonstrated here the possibility to store mouse spermatozoa for up to five years in a −80°C freezer with no significant differences compared to the storage in LN2 in terms of fertilizing ability, sperm viability, intracellular calcium concentration, membrane lipid disorder, and mitochondrial activity.
Altered presentation of oropharyngeal cancer, a 6‐year review
Authors: Floros Peter , Rao Amshuman , McCloy Rachael A. , Sim Hao‐Wen , Chin Venessa T. , Leavers Brett C. , Crawford Julia A. , Gallagher Richard M.
Published: January 2021

Background

Human papilloma virus (HPV)‐associated oropharyngeal squamous cell carcinoma (OPSCC) continues to increase in incidence. Patients are younger, non‐smokers and most commonly present with a neck mass often with no other symptoms. This altered presentation compared with non‐HPV OPSCC may not be recognized by medical practitioners, leading to delayed diagnosis.

Methods

Patients with histopathological confirmation of OPSCC and known HPV and/or P16 status who presented to our institution between 2012–2017 inclusive were included in the study. Demographic data, tumour characteristics and presenting symptoms were retrospectivxely obtained from both electronic‐ and paper‐based records. Descriptive statistics were used to report demographic data and the two sample t‐test and Fisher's exact test were used to compare groups based on HPV status. Time to diagnosis was also reported.

Results

A total of 184 patients were included in the study. The majority of patients were male (85.4%) and HPV + (85.3%). The tonsillar complex (53.8%) and tongue base (42.4%) were the most common primary sites. HPV+ patients were less likely to smoke (17.8%) and they commonly presented with a neck mass (39.5% alone or with other symptoms 61.2%). Time to diagnosis in the HPV+ group was longer (15 weeks).

Conclusion

Our review has highlighted the altered presentation of OPSCC due to the increased incidence of HPV infection. We showed a delayed time to diagnosis in HPV+ OPSCC compared with non‐HPV disease. This confirms the importance of focusing our efforts on educating medical practitioners and creating further awareness to facilitate early detection and treatment.
Cardiopulmonary bypass‐induced coagulopathy in pediatric patients: The role of platelets in postoperative bleeding. A preliminary study
Authors: Di Gregorio Guido , Sella Nicolò , Spiezia Luca , Menin Eugenia , Boscolo Annalisa , Pasin Laura , Pittarello Demetrio , Vida Vladimiro , Simioni Paolo , Navalesi Paolo
Published: January 2021

Pediatric patients are particularly prone to cardiopulmonary bypass (CPB)‐induced coagulopathy mainly due to hemodilution, consumption of coagulation factors and hypothermia. The aim of the present study was to examine the possible role of platelet count and function as it relates to the bleeding risk after CPB in the pediatric population. All consecutive patients (age <13 years) scheduled for elective cardiac surgery between January 2019 and November 2019 were retrospectively considered for the study. We gathered demographic characteristics, perioperative laboratory data (mainly platelet count and function), transfusion requirements, and blood loss for each patient. Patients with a chest tube output during the first 24 hours after surgery >75th percentile were bleeders (cases). Controls were nonbleeders. A total of 31 patients were enrolled [median age 17 (4‐57) months]. A significant postoperative reduction in platelet count (P < .001) and function either in ADP‐test (P < .001), TRAP‐test (P < .001) and ASPI‐test (P < .001) was found, with positive correlations between chest tube output within the first 24 hours after surgery and postoperative impairment of platelet count (R = 0.553, P = .001), ADP‐test (R = 0.543, P = .001), TRAP‐test (R = 0.627, P < .001) and ASPI‐test (R = 0.436, P = .014). Eight children (26%) experienced major postoperative bleeding. Bleeders were significantly younger (P = .015) and underwent longer CPB duration (P = .015). Despite no significant differences in postoperative platelet count and function between cases and controls, the postoperative reduction (Δ) in platelet count (P = .002) and function in ADP‐test (P = .007), TRAP‐test (P = .020) and ASPI‐test (P = .042) was significantly greater in bleeders vs. nonbleeders. A ΔPLT >262 500 ×109/L, a ΔADP‐test >29 U, a ΔTRAP‐test >44 U and a ΔASPI‐test >26 U showed to be predictive of major postoperative bleeding. Postoperative bleeding in children undergoing cardiac surgery with CPB was linked to younger age, longer CPB duration, and significant postoperative reduction in platelet count and function. Larger studies are needed to confirm our results and define strategies to reduce postoperative bleeding in these patients.
Evaluation of real‐time thrombus detection method in a magnetically levitated centrifugal blood pump using a porcine left ventricular assist circulation model
Authors: Seki Haruna , Fujiwara Tatsuki , Hijikata Wataru , Murashige Tomotaka , Tahara Tomoki , Yokota Sachie , Ogata Asato , Ohuchi Katsuhiro , Mizuno Tomohiro , Arai Hirokuni
Published: January 2021

Pump thrombosis induces significant complications and requires timely detection. We proposed real‐time monitoring of pump thrombus in a magnetically levitated centrifugal blood pump (mag‐lev pump) without using additional sensors, by focusing on the changes in the displacement of the pump impeller. The phase difference between the current and displacement of the impeller increases with pump thrombus. This thrombus detection method was previously evaluated through simulated circuit experiments using porcine blood. Evaluation of real‐time thrombus detection in a mag‐lev blood pump was performed using a porcine left ventricular assist circulation model in this study. Acute animal experiments were performed five times using five Japanese domestic pigs. To create thrombogenic conditions, fibrinogen coating that induces thrombus formation in a short time was applied to the inner surfaces of the pump. An inflow and an outflow cannula were inserted into the apex of the left ventricle and the carotid artery, respectively, by a minimally invasive surgical procedure that allowed minimal bleeding and hypothermia. Pump flow was maintained at 1 L/min without anticoagulation. The vibrational frequency of the impeller (70 Hz) and its vibrational amplitude (30 μm) were kept constant. The thrombus was detected based on the fact that the phase difference between the impeller displacement and input current to the magnetic bearing increases when a thrombus is formed inside a pump. The experiment was terminated when the phase difference increased by over 1° from the lowest value or when the phase difference was at the lowest value 12 hours after commencing measurements. The phase difference increased by over 1° in three cases. The pump was stopped after 12 hours in two cases. Pump thrombi were found in the pump in three cases in which the phase difference increased by over 1°. No pump thrombus was found in the other two cases in which the phase difference did not increase. We succeeded in real‐time thrombus monitoring of a mag‐lev pump in acute animal experiments.