bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic significance of MR identified EMVI, tumour deposits, mesorectal nodes and pelvic side wall disease in locally advanced rectal cancer
Authors: Chandramohan Anuradha , Mittal Rohin , Dsouza Romina , Yezzaji Harish , Eapen Anu , Simon Betty , John Reetu , Singh Ashish , Ram Thomas S. , Jesudason Mark R. , Masih Dipti , Karuppusami Reka
Published: December 2021

Aim

To study the prognostic significance of MRI identified tumour deposits (TD), extramural vascular invasion (EMVI), lymph node metastases (LNM) and pelvic sidewall (PSW) disease in rectal cancer.

Methods

This IRB approved study was conducted on patients with stage IIA–IIIC rectal adenocarcinoma treated with neoadjuvant long course chemoradiotherapy (LCCRT) and total mesorectal excision (TME) type of surgery between 2012–2018. A radiologist blinded to outcome reviewed staging and restaging magnetic resonance imaging (MRI) for TD, EMVI, LNM and PSW. The agreement between four radiologists was studied and we obtained outcome data from a prospectively maintained database. The prognostic significance of imaging findings was assessed.

Results

A total of 297 (186 males) patients with a mean age of 47.3 (SD14.4) years were included in the study. The majority had T3 (n = 206) or T4 (n = 59) stage disease. The mean duration of follow‐up was 49.3 ± 25 months (6.6–101 months). 5‐year overall (OS) and disease‐free survival (DFS) was 84% and 74%, respectively. Staging and restaging MRI had EMVI in 49.5% and 31.3%; TD in 47.5% and 31.6%; LNM in 61.1% and 38.1% and PSW in 11.4% and 6.1%. OS was adversely affected by EMVI, TD and PSW with the adjusted HR (aHR) of 3.32, 3.31, 3.27 for staging MRI and 2.99, 3.1, 2.81 for restaging MRI, respectively, p < 0.05. DFS was affected by EMVI (aHR = 1.85, 2.33) and TD (aHR = 1.83, 2.19), p < 0.05. Persistence of these findings after LCCRT led to worst outcome. Intra‐ and interobserver agreement for EMVI, TD and LN was 0.789, 0.734, 0.406 and 0.449, 0.354, 0.376, respectively, p < 0.001.

Conclusions

MRI identified that TD, EMVI and PSW disease are independent poor prognostic indicators in rectal cancer patients. Interobserver agreement for these findings was moderate to fair.
Technology and task changes in the major EU countries
Authors: De Nardis Sergio , Parente Francesca
Published: December 2021

Drawing on the Acemoglu–Restrepo framework, this article investigates the influence of technological innovations on the wage bill of France, Germany, Italy and Spain We show that in these countries: (a) the wage‐bill deceleration since the 1990s has mainly been productivity driven; (b) but was also affected by a wage‐share compression; (c) contraction of labor‐intensive tasks played a relevant role in such compression; (d) this reflected an acceleration of technology‐induced labor displacement not sufficiently offset by the reinstatement of new labor‐intensive tasks; (e) labor displacement was higher in low‐end services. Econometric analysis of displacement confirms the influence of technology.
Transcriptional analysis identifies potential novel biomarkers associated with successful ex‐vivo perfusion of human donor lungs
Authors: Ferdinand John Robert , Morrison Morvern Isabel , Andreasson Anders , Charlton Catriona , Chhatwal Alisha Kaur , Scott William Earl , Borthwick Lee Anthony , Clatworthy Menna Ruth , Fisher Andrew J.
Published: December 2021

Background

Transplantation is an effective treatment for end‐stage lung disease, but the donor organ shortage is a major problem. Ex‐vivo lung perfusion (EVLP) of extended criteria organs enables functional assessment to facilitate clinical decision‐making around utilization, but the molecular processes occurring during EVLP, and how they differ between more or less viable lungs, remain to be determined.

Methods

We used RNA sequencing of lung tissue to delineate changes in gene expression occurring in 10 donor lungs undergoing EVLP and compare lungs that were deemed non‐transplantable (n = 4) to those deemed transplantable (n = 6) following perfusion.

Results

We found that lungs deemed unsuitable for transplantation had increased induction of innate immune pathways and lower expression of oxidative phosphorylation related genes. Furthermore, the expression of SCGB1A1, a gene encoding an anti‐inflammatory secretoglobin CC10, and other club cell genes was significantly decreased in non‐transplantable lungs, while CHIT‐1 was increased. Using a larger validation cohort (n = 17), we confirmed that the ratio of CHIT1 and SCGB1A1 protein levels in lung perfusate have potential utility to distinguish transplantable from non‐transplantable lungs (AUC .81).

Conclusions

Together, our data identify novel biomarkers that may assist with pre‐transplant lung assessment, as well as pathways that may be amenable to therapeutic intervention during EVLPAQ6.
Exenatide‐induced granulomatous panniculitis associated with poly(d,l‐lactide‐co‐glycolide)
Authors: Zhu Caroline S. , Kwan Eddie A. , Williams Grant M. , Lewin‐Smith Michael , Lincoln Mark S. , Lee Abigail J.
Published: December 2021

The extended‐release formulation of exenatide for treatment of Type II diabetes mellitus is encapsulated in microspheres composed of poly(d,l‐lactide‐co‐glycolide) (PLGA) and administered weekly. This medication has been reported to potentially cause injection‐site reactions such as pruritus, transient nodules, and foreign body reaction. Here, we report a case of exenatide‐induced granulomatous panniculitis. Our patient is a 63‐year‐old female with Type II diabetes presenting for concerns about painful nodules on her abdomen, developing approximately every week over the past year and migrating. Of note, the lesions appeared following exenatide injections in the same locations. Two deep‐seated nodules of 1 cm were identified on examination. There were no overlying skin changes, and the lesions were tender to palpation. Punch biopsies of the two lesions were performed, which revealed a septal panniculitis containing amorphous material, along with a mixed inflammatory infiltrate. Gomori methenamine silver (GMS) and acid‐fast bacilli (AFB) stains were negative for organisms. On infrared (IR) spectroscopy examination of the biopsy tissue, the spectral characteristics of (tissue) protein and PLGA were seen. Evaluation of the clinical and histopathologic findings, along with the IR spectroscopy match, determined that exenatide‐induced panniculitis was the cause of the patient's nodules. This case highlights the importance of clinicians' awareness regarding injection‐site reactions.
Understanding autonomous behaviour development: Exploring the developmental contributions of context‐tracking and task selection to self‐directed cognitive control
Authors: Frick Aurélien , Brandimonte Maria A. , Chevalier Nicolas
Published: December 2021

Gaining autonomy is a key aspect of growing up and cognitive control development across childhood. However, little is known about how children engage cognitive control in an autonomous (or self‐directed) fashion. Here, we propose that in order to successfully engage self‐directed control, children identify, and achieve goals by tracking contextual information and using this information to select relevant tasks. To disentangle the respective contributions of these processes, we manipulated the difficulty of context‐tracking via altering the presence or absence of contextual support (Study 1) and the difficulty of task selection by varying task difficulty (a)symmetry (Study 2) in 5–6 and 9‐10‐year‐olds, and adults. Results suggested that, although both processes contribute to successful self‐directed engagement of cognitive control, age‐related progress mostly relates to context‐tracking.
Reconceptualising dentist learning–A commentary
Authors: Goh Adeline Yuen Sze , Lim Alistair Daniel
Published: December 2021

Professional bodies and organisations increasingly require health care professionals, including dentists, to account for their learning as part of mandatory continuing professional development (CPD) requirements. In recent years, there has been a shift from an input‐based model to an outcome‐ based model in order to respond to the needs of dental professionals. In this commentary, we aim to explore the learning assumptions inscribed in these models for CPD. Drawing on one of the authors' dental work experiences and contemporary professional learning literature, we hope to incite discussions on widening our perspectives about dentists’ professional learning and the implications for CPD.
Multi‐scaled feature fusion enabled convolutional neural network for predicting fibrous dysplasia bone disorder
Authors: Arirangan Saranya , Kottursamy Kottilingam
Published: December 2021

Background

Convolutional Neural Network (CNN) has exciting advantages in the processing of medical images. It produces the denoised and segmented results of images. When an image has orientation and scaling issues over the bundle that is not correctly recognized by the classifier.

Methods

To overcome these issues, we propose Extreme Deep Learning on Feature Fusion Convolutional Neural Network (EDL‐FFCNN) for classification. Feature fusion workflow enhances the ability to learn the feature from the inconsistent behaviour. And, to learn the texture, colour, and intensities of an image. The initial step of the FFCNN framework is to reconstruct the images using filtered back projection. It reduces the noise in edges and cross‐sectional areas. Contrast Limited Adaptive Histogram Equalization and Local Binary Pattern is applied to an image to adjust and extract the intensity and textural features of an image. The proposed FFCNN is a decision‐based approach that consists of two persistent classifiers. One, the convolutional features are combined with manually extracted multi‐scaled features. Subsequently, the normalization techniques are built‐in every layer to adjust the input dimensions. It also helps to reduce the training time. As an outcome of Image abnormalities is considered as knowledge transfer to the CNN.

Results

The fused features on the CNN classifier produce the abnormality prediction results. Second, the Inception V2 CNN classifier framework classifies the bone images with extracted features. With these two comparative‐classification results, the major counting has been taken as the decision for final abnormality prediction. The proposed model gives improved accuracy of 95% for the elbow, 93% for the forearm, 92% for the shoulder, 92% for the wrist, 93% for the finger, 92% for humerus images.
Biophysical investigation of the dual binding surfaces of human transcription factors FOXO4 and p53
Authors: Kim Jinwoo , Ahn Dabin , Park Chin‐Ju
Published: December 2021

Cellular senescence is protective against external oncogenic stress, but its accumulation causes aging‐related diseases. Forkhead box O4 (FOXO4) and p53 are human transcription factors known to promote senescence by interacting with each other and activating p21 transcription. Inhibition of the interaction is a strategy for inducing apoptosis of senescent cells, but the binding surfaces that mediate the FOXO4–p53 interaction remain elusive. Here, we investigated two binding sites involved in the interaction between FOXO4 and p53 by NMR spectroscopy. NMR chemical shift perturbation analysis showed that the binding between FOXO4’s forkhead domain (FHD) and p53’s transactivation domain (TAD), and between FOXO4’s C‐terminal transactivation domain (CR3) and p53’s DNA‐binding domain (DBD), mediate the FOXO4–p53 interaction. Isothermal titration calorimetry data showed that both interactions have micromolar Kd values, and FOXO4 FHD–p53 TAD interaction has a higher binding affinity. We also showed that the intramolecular CR3‐binding surface of FOXO4 FHD interacts with p53 TAD2, and FOXO4 CR3 interacts with the DNA/p53 TAD‐binding surface of p53 DBD, suggesting a network of potentially competitive and/or coordinated interactions. Based on these results, we propose that a network of intramolecular and intermolecular interactions contributes to the two transcription factors’ proper localisation on the p21 promoter and consequently promotes p21 transcription and cell senescence. This work provides structural information at the molecular level that is key to understanding the interplay of two proteins responsible for cellular senescence.
EHMT1/EHMT2 in EMT, cancer stemness and drug resistance: emerging evidence and mechanisms
Authors: Nachiyappan Alamelu , Gupta Neelima , Taneja Reshma
Published: December 2021

Metastasis, therapy failure and tumour recurrence are major clinical challenges in cancer. The interplay between tumour‐initiating cells (TICs) and epithelial–mesenchymal transition (EMT) drives tumour progression and spread. Recent advances have highlighted the involvement of epigenetic deregulation in these processes. The euchromatin histone lysine methyltransferase 1 (EHMT1) and euchromatin histone lysine methyltransferase 2 (EHMT2) that primarily mediate histone 3 lysine 9 di‐methylation (H3K9me2), as well as methylation of non‐histone proteins, are now recognised to be aberrantly expressed in many cancers. Their deregulated expression is associated with EMT, cellular plasticity and therapy resistance. In this review, we summarise evidence of their myriad roles in cancer metastasis, stemness and drug resistance. We discuss cancer‐type specific molecular targets, context‐dependent mechanisms and future directions of research in targeting EHMT1/EHMT2 for the treatment of cancer.
Biochemical propensity mapping for structural and functional anatomy of importin α IBB domain
Authors: Jibiki Kazuya , Liu Mo‐yan , Lei Chao‐sen , Kodama Takashi S. , Kojima Chojiro , Fujiwara Toshimichi , Yasuhara Noriko
Published: December 2021

Importin α has been described as a nuclear protein transport receptor that enables proteins synthesized in the cytoplasm to translocate into the nucleus. Besides its function in nuclear transport, an increasing number of studies have examined its non‐nuclear transport functions. In both nuclear transport and non‐nuclear transport, a functional domain called the IBB domain (importin β binding domain) plays a key role in regulating importin α behavior, and is a common interacting domain for multiple binding partners. However, it is not yet fully understood how the IBB domain interacts with multiple binding partners, which leads to the switching of importin α function. In this study, we have distinguished the location and propensities of amino acids important for each function of the importin α IBB domain by mapping the biochemical/physicochemical propensities of evolutionarily conserved amino acids of the IBB domain onto the structure associated with each function. We found important residues that are universally conserved for IBB functions across species and family members, in addition to those previously known, as well as residues that are presumed to be responsible for the differences in complex‐forming ability among family members and for functional switching.
Feminism from the margins: How women are contesting the “othering” of Muslims through arts‐based resistance?
Authors: Kumar Ritesh , Kamble Rahul
Published: December 2021

This paper captures how a women's protest offered resistance to the ethnonationalist state's exclusionary citizenship policy that seeks to disqualify Muslims from citizenship rights and entitlements in postcolonial India. Since the pre‐pandemic period, Muslim women have been contesting this ideological play of the sovereign state power through various cultural and political framing of counter‐narratives through various art forms, including poetry, poetic practices, and graffiti. We argue that this arts‐based resistance has significant implication for how grassroots feminist movements discursively mobilizes theory and practice to build feminist consciousness and solidarity among this minority community as well as create coalitions and networks with broader communities of different faiths. Poetry, poetic practice, and graffiti provide the communicative platform to voice against injustice and violence by those in power. We contribute to the debates on writing differently by integrating the poems and graffiti as an empirical source that brings forth collective experiences to engender empathy and the hope to resist structures of hegemony.
An updated review on efficacy and benefits of sweet almond, evening primrose and jojoba oils in skin care applications
Authors: Blaak Jürgen , Staib Peter
Published: December 2021

Background

Renewed consumer and industry interest in natural ingredients has led to a large growth of natural cosmetics. This has put pressure on formulation skills and product claims when it comes to using natural compounds. Taking a strategic and comprehensive approach in viewing natural ingredients, including natural oils, as ‘active’ ingredients rather than just providing for so‐called ‘natural’ claims, aids both innovation and development. Given the ever‐increasing consumer demand for natural ingredients, and more importantly the demand for effective natural ingredients including plant oils, it is important for the cosmetic industry to re‐evaluate them in this context.

Method

The objectives of this review are to provide an update of three popular cosmetic plant oils – Sweet Almond, Evening Primrose and Jojoba – in terms of their cosmetic applications as ‘active’ ingredients. This review highlights the activity of these oils, in the management of dry skin, ageing skin, juvenile skin, atopic dermatitis, scalp conditions and their wider potential. Attention is given to formulation considerations where the content of these oils impacts product oxidation, skin penetration and stratum corneum homeostasis.

Results

Benefits of these oils have been well documented both pre‐clinically and clinically. Historically, they have been used for hundreds if not thousands of years for their management and treatment of various skin and other ailments. Given the discrepancies in some clinical data presented for a variety of dermatoses, the importance of the choice of oil and how to formulate with them within the context of the epidermal barrier function, skin penetration and toxicity cannot be underestimated. Care should be taken in terms of the quality and stability of theses oils, as well as ensuring best formulation type, if the reported activities of these oils are to be achieved with consistency. Despite discrepancies in the literature and questionable study designs, it is clear that Sweet Almond, Evening Primrose and Jojoba oils do have skin care benefits for both adult and juvenile applications.

Conclusion

They are effective ingredients for skin care preparations to strengthen stratum corneum integrity, recovery and lipid ratio. Nevertheless, further experimental data are required concerning the impact on stratum corneum physiology and structure.
Wear and fracture of curettes due to sharpening and scaling processes
Authors: Liu Guojing , Liu Xueling , Li Na , Gao Chengcheng , Cui Ting , Luan Qingxian , Wang Jianmin
Published: December 2021

Objectives

To examine the wear occurring in a group of new Gracey curettes due to the sharpening and scaling processes and record the number of service cycles before breakage.

Methods

This study included 592 working ends of Gracey curettes that were subjected to cycles of sharpening and scaling. Three‐dimensional measurements of the blades and the status of the working ends were recorded before and after each process.

Results

With an increase in the number of usage cycles, the three‐dimensional measurements of the blades decreased. During this study, 184 working ends were broken, of which 38.59% were of #11/12 Gracey curettes, and only 8.15% were of #7/8 Gracey curettes. The average number of cycles required for the fracture of Gracey curettes was 14.34. Cox regression analyses showed that the factors influencing the survival cycles were the tip width before usage and the type of Gracey curette. Moreover, the sharpening process was responsible for approximately half of the total instrument wear. Among the four types of Gracey curettes, the #11/12 Gracey curettes showed the greatest amount of sharpening wear, accounting for >50% of the total wear.

Conclusions

The service life of Gracey curettes varies according to their types; the #11/12 Gracey curettes are more susceptible to breakage, while #7/8 Gracey curettes tend to have a long service life. Furthermore, the sharpening process was responsible for a considerable amount of curette wear.
Microbial traces and their role in forensic science
Authors: Speruda Mateusz , Piecuch Agata , Borzęcka Justyna , Kadej Marcin , Ogórek Rafał
Published: December 2021

Forensic microbiology, also known as the microbiology of death, is an emerging branch of science that is still underused in criminal investigations. Some of the cases might be difficult to solve with commonly used forensic methods, and then they become an operational field for microbiological and mycological analyses. The aim of our review is to present significant achievements of selected studies on the thanatomicrobiome (micro-organisms found in the body, organs and fluids after death) and epinecrotic community (micro-organisms found on decaying corpses) that can be used in forensic sciences. Research carried out as a part of the forensic microbiology deals with the thanatomicrobiome and the necrobiome—communities of micro-organisms that live inside and outside of a putrefying corpse. Change of species composition observed in each community is a valuable feature that gives a lot of information related to the crime. It is mainly used in the estimation of post-mortem interval (PMI). In some criminal investigations, such noticeable changes in the microbiome and mycobiome can determine the cause or the actual place of death. The microbial traces found at the crime scene can also provide clear evidence of guilt. Nowadays, identification of micro-organisms isolated from the body or environment is based on metagenome analysis and 16S rRNA gene amplicon-based sequencing for bacteria and ITS rRNA gene amplicon-based sequencing for fungi. Cultivation methods are still in use and seem to be more accurate; however, they require much more time to achieve a final result, which is an unwanted feature in any criminal investigation.
Trait‐based response of lichens to large‐scale patterns of climate and forest availability in Norway
Authors: Phinney Nathan H. , Ellis Christopher J. , Asplund Johan
Published: December 2021

Aim

Functional traits offer a window into how organisms are adapted, and might acclimate, to environmental pressures. Despite being important in ecosystem function, lichens are underrepresented in trait‐based research; understanding how lichen functional traits vary with climate and habitat availability will be useful in predicting how communities will respond to climate change, for example, in wetter and warmer boreal and arctic ecosystems. Here, we assess the influence of macroclimate and forest availability on the spatial distribution of lichen traits across Norway.

Location

Norwegian mainland.

Taxon

Lichens.

Methods

We used relative trait frequency (RTF) data from LIAS gtm, a database combining trait information from LIAS (A Global Information System for Lichenized and Non‐Lichenized Ascomycetes) and GBIF (Global Biodiversity Information Facility) species observations. The 20 traits included photobiont types, growth forms, cortical features and reproductive modes. Nonparametric multiplicative regression (NPMR) models were used to explore the relationships between the environmental predictors of precipitation, temperature and forest availability.

Results

All traits showed significant relationships with the three environmental predictors. Photobiont type and reproductive mode traits produced the strongest models and revealed ecologically meaningful biogeographical patterns. Trebouxioid species peaked in colder, drier upland regions, while trentepohlioid lichens displayed an affinity for wetter and warmer climates and had a western and southern distribution. Cyanolichens increased with increasing precipitation and were strongly coastal. Sorediate and isidiate lichens were positively related to temperature, the former also increasing with forest cover. The above responses were consistent with the physiological and habitat requirements of the associated lichens. The remaining traits had weaker responses.

Main conclusions

Discrete traits (i.e. photobiont type and reproductive mode) with relatively low ecological plasticity reflect clear functional environmental responses at the large scale. By contrast, growth form and thallus structural features—proxies for continuous variables—are too variable within each given category to show observable distribution patterns.
Interfering with mitochondrial dynamics sensitizes glioblastoma multiforme to temozolomide chemotherapy
Authors: Wang Nan , Huang Renxuan , Yang Kunmeng , He Yichun , Gao Yufei , Dong Delu
Published: December 2021

Glioblastoma multiforme (GBM) is a primary tumour of the central nervous system (CNS) that exhibits the highest degree of malignancy. Radiotherapy and chemotherapy are essential to prolong the survival time of patients. However, clinical work has demonstrated that sensitivity of GBM to chemotherapy decreases with time. The phenomenon of multi‐drug resistance (MDR) reminds us that there may exist some fundamental mechanisms in the process of chemo‐resistance. We tried to explore the mechanism of GBM chemo‐resistance from the perspective of energy metabolism. First, we found that the oxidative phosphorylation (OXPHOS) level of SHG44 and U87 cells increased under TMZ treatment. In further studies, it was found that the expression of PINK1 and mitophagy flux downstream was downregulated in GBM cells, which were secondary to the upregulation of TP53 in tumour cells under TMZ treatment. At the same time, we examined the mitochondrial morphology in tumour cells and found that the size of mitochondria in tumour cells increased under the treatment of TMZ, which originated from the regulation of AMPK on the subcellular localization of Drp1 under the condition of unbalanced energy supply and demand in tumour cells. The accumulation of mitochondrial mass and the optimization of mitochondrial quality accounted for the increased oxidative phosphorylation, and interruption of the mitochondrial fusion process downregulated the efficiency of oxidative phosphorylation and sensitized GBM cells to TMZ, which was also confirmed in the in vivo experiment. What is more, interfering with this process is an innovative strategy to overcome the chemo‐resistance of GBM cells.
Capital and Closure in the EU Field. Advancement in the European Economic and Social Committee
Authors: Johansson Håkan , Uhlin Anders , Arvidson Malin
Published: December 2021

This article explores what it takes to advance to the top of an EU institution (European Economic and Social Committee). The article combines Bourdieu’s theories of field and capital with Weber’s theory of social closure to study the interplay between required forms of capital and closure practices during three ideal‐typical phases of upward mobility: ‘getting in’, ‘fitting in’ and ‘moving on’. Drawing on 26 semi‐structured interviews, the article finds that capital and closure are mutually interdependent as members’ access to capital to advance depends on whether they pass the closure tests deployed by closure agents and manage to get in, fit in and move on in the EU field. By combining capital and closure approaches, the article suggests a new balance between structure and actor‐centred theories, which can help us better capture what is at stake in the EU field, and how the game of career advancement is played.
Persistence of Trypanosoma brucei as early procyclic forms and social motility are dependent on glycosylphosphatidylinositol transamidase
Authors: Knüsel Sebastian , Jenni Aurelio , Benninger Mattias , Bütikofer Peter , Roditi Isabel
Published: December 2021

Glycosylphosphatidylinositol (GPI)‐linked molecules are surface‐exposed membrane components that influence the infectivity, virulence and transmission of many eukaryotic pathogens. Procyclic (insect midgut) forms of Trypanosoma brucei do not require GPI‐anchored proteins for growth in suspension culture. Deletion of TbGPI8, and inactivation of the GPI:protein transamidase complex, is tolerated by cultured procyclic forms. Using a conditional knockout, we show TbGPI8 is required for social motility (SoMo). This collective migration by cultured early procyclic forms has been linked to colonization of the tsetse fly digestive tract. The SoMo‐negative phenotype was observed after a lag phase with respect to loss of TbGPI8 and correlated with an unexpectedly slow loss of procyclins, the major GPI‐anchored proteins. Procyclins are not essential for SoMo, however, suggesting a requirement for at least one other GPI‐anchored protein. Loss of TbGPI8 initiates the transition from early to late procyclic forms; this effect was observed in a subpopulation in suspension culture, and was more pronounced when cells were cultured on SoMo plates. Our results indicate two, potentially interlinked, scenarios that may explain the previously reported failure of TbGPI8 deletion mutants to establish a midgut infection in the tsetse fly: interference with stage‐specific gene expression and absence of SoMo.
Rotavirus activates MLKL‐mediated host cellular necroptosis concomitantly with apoptosis to facilitate dissemination of viral progeny
Authors: Mukhopadhyay Urbi , Patra Upayan , Chandra Pritam , Saha Priyanka , Gope Animesh , Dutta Moumita , Chawla‐Sarkar Mamta
Published: December 2021

Reprogramming the host cellular environment is an obligatory facet of viral pathogens to foster their replication and perpetuation. One of such reprogramming events is the dynamic cross‐talk between viruses and host cellular death signaling pathways. Rotaviruses (RVs) have been reported to develop multiple mechanisms to induce apoptotic programmed cell death for maximizing viral spread and pathogenicity. However, the importance of non‐apoptotic programmed death events has remained elusive in context of RV infection. Here, we report that RV‐induced apoptosis accompanies another non‐apoptotic mode of programmed cell death pathway called necroptosis to promote host cellular demise at late phase of infection. Phosphorylation of mixed lineage kinase domain‐like (MLKL) protein indicative of necroptosis was observed to concur with caspase‐cleavage (apoptotic marker) beyond 6 hr of RV infection. Subsequent studies demonstrated phosphorylated‐MLKL to oligomerize and to translocate to plasma membrane in RV infected cells, resulting in loss of plasma membrane integrity and release of alarmin molecules e.g., high mobility group box protein 1 (HMGB1) in the extracellular media. Moreover, inhibiting caspase‐cleavage and apoptosis could not fully rescue virus‐induced cell death but rather potentiated the necroptotic trigger. Interestingly, preventing both apoptosis and necroptosis by small molecules significantly rescued virus‐induced host cytopathy by inhibiting viral dissemination.
Highly efficient genome editing in Xanthomonas oryzae pv. oryzae through repurposing the endogenous type I‐C CRISPR‐Cas system
Authors: Jiang Dandan , Zhang Dandan , Li Shengnan , Liang Yueting , Zhang Qianwei , Qin Xu , Gao Jinlan , Qiu Jin‐Long
Published: December 2021

Efficient and modular genome editing technologies that manipulate the genome of bacterial pathogens will facilitate the study of pathogenesis mechanisms. However, such methods are yet to be established for Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of rice bacterial blight. We identified a single type I‐C CRISPR‐Cas system in the Xoo genome and leveraged this endogenous defence system for high‐efficiency genome editing in Xoo. Specifically, we developed plasmid components carrying a mini‐CRISPR array, donor DNA, and a phage‐derived recombination system to enable the efficient and programmable genome editing of precise deletions, insertions, base substitutions, and gene replacements. Furthermore, the type I‐C CRISPR‐Cas system of Xoo cleaves target DNA unidirectionally, and this can be harnessed to generate large genomic deletions up to 212 kb efficiently. Therefore, the genome‐editing strategy we have developed can serve as an excellent tool for functional genomics of Xoo, and should also be applicable to other CRISPR‐harbouring bacterial plant pathogens.
The cap‐snatching frequency of a plant bunyavirus from nonsense mRNAs is low but is increased by silencing of UPF1 or SMG7
Authors: Jin Jing , She Yuanyuan , Qiu Ping , Lin Wenzhong , Zhang Wenwen , Zhang Jie , Wu Zujian , Du Zhenguo
Published: December 2021

Bunyaviruses cleave host cellular mRNAs to acquire cap structures for their own mRNAs in a process called cap‐snatching. How bunyaviruses interact with cellular mRNA surveillance pathways such as nonsense‐mediated decay (NMD) during cap‐snatching remains poorly understood, especially in plants. Rice stripe virus (RSV) is a plant bunyavirus threatening rice production in East Asia. Here, with a newly developed system allowing us to present defined mRNAs to RSV in Nicotiana benthamiana, we found that the frequency of RSV to target nonsense mRNAs (nsRNAs) during cap‐snatching was much lower than its frequency to target normal mRNAs. The frequency of RSV to target nsRNAs was increased by virus‐induced gene silencing of UPF1 or SMG7, each encoding a protein component involved in early steps of NMD (in an rdr6 RNAi background). Coincidently, RSV accumulation was increased in the UPF1‐ or SMG7‐silenced plants. These data indicated that the frequency of RSV to target nsRNAs during cap‐snatching is restricted by NMD. By restricting the frequency of RSV to target nsRNAs, NMD may impose a constraint to the overall cap‐snatching efficiency of RSV. Besides a deeper understanding for the cap‐snatching of RSV, these findings point to a novel role of NMD in plant–bunyavirus interactions.
Characterisation of rapid alkalinisation factors in Physcomitrium patens reveals functional conservation in tip growth
Authors: Ginanjar Eggie Febrianto , Teh Ooi‐kock , Fujita Tomomichi
Published: December 2021

Small signalling peptides are key molecules for cell‐to‐cell communications in plants. The cysteine‐rich signalling peptide, rapid alkalinisation factors (RALFs) family are involved in diverse developmental and stress responses and have expanded considerably during land plant evolution, implying neofunctionalisations in the RALF family. However, the ancestral roles of RALFs when land plant first acquired them remain unknown.

Here, we functionally characterised two of the three RALFs in bryophyte Physcomitrium patens using loss‐of‐function mutants, overexpressors, as well as fluorescent proteins tagged reporter lines.

We showed that PpRALF1 and PpRALF2 have overlapping functions in promoting protonema tip growth and elongation, showing a homologous function as the Arabidopsis RALF1 in promoting root hair tip growth. Although both PpRALFs are secreted to the plasma membrane on which PpRALF1 symmetrically localised, PpRALF2 showed a polarised localisation at the growing tip. Notably, proteolytic cleavage of PpRALF1 is necessary for its function.

Our data reveal a possible evolutionary origin of the RALF functions and suggest that functional divergence of RALFs is essential to drive complex morphogenesis and to facilitate other novel processes in land plants.
A generalist nematode destabilises plant competition: no evidence for direct effects, but strong evidence for indirect effects on rhizobium abundance
Authors: Catella Samantha A. , Olmsted Castilleja Fallon , Markalanda Shaniya H. , McFadden Connor J. , Wood Corlett W. , Kuebbing Sara E.
Published: December 2021

Difficulties quantifying pathogen load and mutualist abundance limit our ability to connect disease dynamics to host community ecology. For example, specific predictions about how differential pathogen load is hypothesised to drive host competitive outcomes are rarely tested. Additionally, although infection is known to affect mutualists, we rarely measure the magnitude of pathogen effects on mutualist abundance across host competitive contexts. We tested for both mechanisms in a plant–rhizobia–nematode system.

We paired the legume Medicago lupulina with intraspecific and interspecific plant competitors, with and without a generalist nematode parasite Meloidogyne sp. Relative change in plant biomass was used to determine how nematode inoculation affected plant competitive outcomes. We counted nematode galls to test for direct effects of parasitism on plant competition and rhizobia nodules to test for indirect effects of nematode presence on rhizobium abundance.

Parasites were destabilising despite similar nematode load across competition treatments. During interspecific compared with intraspecific competition, nematode inoculation decreased nodulation on M. lupulina, increased nodulation on Trifolium repens and had no effect on nodulation on Chamaecrista fasciculata.

We found no support for hypothesised direct effects of nematode load on competitive outcomes and strong but idiosyncratic indirect effects of nematode inoculation on rhizobium abundance.
Efficacy of a 1% malic acid spray for xerostomia treatment: A systematic review and meta‐analysis
Authors: Liu Gang , Qiu Xiaoning , Tan Xinzhi , Miao Rong , Tian Weidong , Jing Wei
Published: December 2021

Objectives

To assess the efficacy of topical sialogogue spray containing malic acid 1% for treating xerostomia.

Methods

We searched PubMed, Cochrane Library, Embase, ClinicalTrials.gov and Web of Science databases. Literature search, screening, study selection, data collection, data extraction and assessment of bias risk were independently conducted by two reviewers. The study appraisal was performed by Cochrane Collaboration's tool for assessing bias risk. The systematic review registration number was PROSPERO‐CRD42021241322. All statistical analyses were performed using Review Manager version 5.4.

Results

Five original articles involving 244 patients with xerostomia who received topical sialogogue spray (malic acid 1%) or placebo for two weeks were included in this review. Based on the questionnaire survey, the topical sialogogue spray (malic acid 1%) improved the symptoms of dry mouth significantly better than the placebo, which was reflected in the Dry Mouth Questionnaire (DMQ), Xerostomia Inventory (XI) and Visual Analogue Scale (VAS) scores. Regarding the increase in unstimulated and stimulated saliva flow rates, the intervention group was also better than the placebo group after a two‐week course of treatment.

Conclusions

Although the included studies are limited, our results show that topical sialogogue spray (malic acid 1%) is an effective method for the treatment of xerostomia. Additional randomised controlled trials in the future are needed to provide high‐quality evidence of this therapy and to improve clinical practice guidelines.
Low vitamin D and high cholesterol facilitate oral carcinogenesis in 4NQO‐induced rat models via regulating glycolysis
Authors: Gumus Rasim , Capik Ozel , Gundogdu Betul , Tatar Arzu , Altinkaynak Konca , Ozdemir Tozlu Ozlem , Karatas Omer Faruk
Published: December 2021

Objectives

Diets and nutritional habits are critical during carcinogenic processes, where a diet poor in fruits and vegetables and rich in meat and other foods of animal origin facilitates carcinogenesis. In this study, we aimed at investigating the possible involvement of vitamin D deficiency (VDD) and high cholesterol (HC) together in oral squamous cell carcinoma (OSCC) through modulating glycolysis.

Subjects and Methods

We compared total cholesterol, LDL, HDL, triglycerides, LDH, and vitamin D levels of OSCC patients and control individuals. We used GEO datasets for gene set enrichment and 4‐nitroquinoline‐1‐oxide induced in vivo oral carcinogenesis models to investigate contribution of VDD and HC during carcinogenesis via possible modulation of glycolysis.

Results

We found that VDD and HC co‐exist in OSCC patients, and deregulation of cholesterol and vitamin D levels results in enrichment of genes related to glycolysis. We, then, demonstrated that VDD and HC on their own and together facilitated the formation of larger tumors in 4NQO‐induced in vivo cancer models, which are suppressed by glycolysis inhibition.

Conclusion

We reported collaborative contribution of HC and VDD during oral carcinogenesis, which is mainly carried out via altering energy metabolism in tumor cells.
Escort of older people into the operating room: A feasibility study
Authors: Shem Tov Lior , Ronel Ilai , Matot Idit
Published: December 2021

Background

While special care is given to perioperative risk assessment and management of older people undergoing surgery, psychological aspects have been largely neglected. Escort presence in the operating room (OR) is common practice in the surgical paediatric and obstetric populations and may be beneficial in older people.

Objectives

This study explored the feasibility of family member escort of older people into the OR and their presence until induction of anaesthesia.

Methods

Prospective observational study of older people (>70 years) undergoing surgery, who were offered an escort into the OR. The primary end point was the proportion of relatives who completed the intervention without feeling dizzy or fainting. Secondary end points related to patient, escort and medical and nursing staff perception of the process.

Results

Forty‐four sets of patients and escorts completed the process. The primary objective assessing feasibility was concluded successfully. Secondary objectives assessed (1) satisfaction, where 93% of escorts and 75% of patients would support a repeat of this process; (2) anxiolysis, where 61% of patients reported a reduced level of anxiety; (3) although 68% of anaesthesiologists agreed this process improved patients' well‐being, most nurses and anaesthesiologists believed this should not become routine practice. Interestingly, most staff support parents escorting a paediatric patient into OR.

Conclusions

This is the first study exploring the feasibility of escorting older people into the OR. It shows a unique insight into patient‐ and family‐centred care of the surgical older person. Escort presence may help alleviate anxiety and increase satisfaction. The medical and nursing staff objections must be looked at further.
The gradual corporatization of transport infrastructure: The Danish case
Authors: Christensen Lene Tolstrup , Grossi Giuseppe
Published: December 2021

The article introduces the theoretical perspective on gradual institutional change to the corporatization literature. This is achieved via a longitudinal case study on the institutionalization of the Danish state guarantee model (SGM) for transport infrastructure based on archival document studies of seven infrastructure projects and 31 interviews with elite actors and experts. The article explores with a detailed analysis how the gradual change mechanisms of layering, conversion and displacement coexist, are interrelated, and are coevolving over a long period. It contributes to the corporatization literature presenting the SGM as an alternative to public and private partnerships and government agencies.
Thoracic regional anesthesia and the impact on ventilation
Authors: Bosenberg Adrian , Holland Erica
Published: December 2021

Thoracic surgical incisions can be associated with intense pain or discomfort. Postoperative thoracic pain may be multifactorial in origin. Inadequate analgesia causes respiratory dysfunction. Adequate analgesia preserves pulmonary function and may hasten recovery. Intravenous opioids are widely used but sufficient analgesia is seldom achieved in doses that permit safe spontaneous ventilation. Thoracic regional anesthesia provides profound analgesia, is opiate sparing and has minimal depressant effects on ventilation. Thoracic regional anesthesia is both an effective alternative to systemic analgesics or can be used as part of a multimodal analgesic technique.
New detections of chestnut blight in Great Britain during 2019–2020 reveal high Cryphonectria parasitica diversity and limited spread of the disease
Authors: Romon‐Ochoa Pedro , Kranjec Orlović Jelena , Gorton Caroline , Lewis Alex , van der Linde Sietse , Pérez‐Sierra Ana
Published: December 2021

Cryphonectria parasitica was detected for the first time in the United Kingdom in 2011. A 2017–2018 survey detected the disease at different sites in Berkshire, Derbyshire, Devon, Dorset and London, while the present study comprises the results of the 2019–2020 survey with new findings and additional sites in the United Kingdom (Berkshire, Buckinghamshire, Cornwall, Derbyshire, Devon, London, West Sussex) and in Jersey, reflecting the progressive detection of more infected trees. A total of 189 samples were collected from 52 sites, and 123 samples tested positive both by quantitative real‐time PCR and/or isolation from 43 sites. A total of 115 isolates were tested for mating type, vegetative compatibility group (VCG) and Cryphonectria hypovirus 1 (CHV‐1). Twelve VCGs were identified, with four of them being first records in United Kingdom. The highest diversity of VCGs was detected in Devon followed by West Sussex while London and Derbyshire presented the lowest. Both mating types were detected (41% MAT‐1 and 59% MAT‐2), and no heterokaryons were detected. Perithecia of C. parasitica were not observed at any site during this survey. CHV‐1 was detected in three isolates in very low concentration from three different locations in London and was always the unmutated subtype I haplotype E‐5. A greater diversity of VCGs at outbreak sites compared with previous surveys, combined with their scattered distribution and the slow spread of the pathogen, supports the hypothesis that this disease has been introduced through imports over time from Europe.
Postural freezing relates to startle potentiation in a human fear‐conditioning paradigm
Authors: van Ast Vanessa A. , Klumpers Floris , Grasman Raoul P. P. P. , Krypotos Angelos‐Miltiadis , Roelofs Karin
Published: December 2021

Freezing to impending threat is a core defensive response. It has been studied primarily using fear conditioning in non‐human animals, thwarting advances in translational human anxiety research that has used other indices, such as skin conductance responses. Here we examine postural freezing as a human conditioning index for translational anxiety research. We employed a mixed cued/contextual fear‐conditioning paradigm where one context signals the occurrence of the US upon the presentation of the CS, and another context signals that the CS is not followed by the US. Critically, during the following generalization phase, the CS is presented in a third and novel context. We show that human freezing is highly sensitive to fear conditioning, generalizes to ambiguous contexts, and amplifies with threat imminence. Intriguingly, stronger parasympathetically driven freezing under threat, but not sympathetically mediated skin conductance, predicts subsequent startle magnitude. These results demonstrate that humans show fear‐conditioned animal‐like freezing responses, known to aid in active preparation for unexpected attack, and that freezing captures real‐life anxiety expression. Conditioned freezing offers a promising new, non‐invasive, and continuous, readout for human fear conditioning, paving the way for future translational studies into human fear and anxiety.