bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome Wide Characterization, Identification And Expression Analysis OfErfGene Family In Cotton
Authors: Zafar Muhammad Mubashar , Rehman Abdul , Razzaq Abdul , Parvaiz Aqsa , Mustafa Ghulam , Mo Huijuan , Youlu Yuan , Shakeel Amir , Ren Maozhi
Published: December 2020

ERFis a subfamily ofAP2/EREBPsuperfamily, contained single AP2 domain. The overexpression ofERFgenes steered to abiotic stress tolerance and pathogen resistance in transgenic plants. Here, a genome-wide analysis ofERFgene family within two diploid species (G. arboreum & G. raimondii) and two tetraploid species (G. barbadense, G. hirsutum) was performed. A total of 118, 120, 213, 220 genes contained sequence single AP2 domain were identified inG. arboreum,G. raimondii,G. barbadenseandG. hirsutumrespectively. The identified genes were unevenly distributed across 13/26 chromosomes of A and D genomes of cotton. Genome comparison revealed that segmental duplication may have played crucial roles in the expansion of the cottonERFgene family, and tandem duplication also played a minor role. Analysis of RNA-Seq data indicated that cottonERFgene expression levels varied across different tissues and in response to different abiotic stress. Overall, our results could provide valuable information for better understanding the evolution of cottonERFgenes and lays a foundation for future investigation in cotton.
Artificial Antigen Presenting Cells for Detection and Desensitisation of Auto-reactive T cells Associated with Type 1 Diabetes
Authors: Artzy-Schnirman Arbel , Abu-Shah Enas , Chandrawati Rona , Altman Efrat , Yusuf Norkhairin , Wang Shih-Ting , Ramos Jose , Hansel Catherine S. , Haus-Cohen Maya , Dahan Rony , Arif Sefina , Dustin Michael L. , Peakman Mark , Reiter Yoram , Stevens Molly M.
Published: December 2020

Autoimmune diseases and in particular type 1 diabetes rely heavily on treatments that target the symptoms rather than prevent the underlying disease. One of the barriers to better therapeutic strategies is the inability to detect and efficiently target rare autoreactive T-cell populations that are major drivers of these conditions. Here, we develop a unique artificial antigen presenting cell (aAPC) system from biocompatible polymer particles that allows specific encapsulation of bioactive ingredients. Using our aAPC we demonstrate that we are able to detect rare autoreactive CD4 populations in human patients and using mouse models we demonstrate that our particles are able to induce desensitization in the autoreactive population. This system provides a promising tool that can be used in the prevention of autoimmunity before disease onset.
Genomic profiling of cancerous patients identifies FPR2 as an alternative immunotherapeutic target in glioblastoma multiforme
Authors: Yang Yuqing , Sun Ting , Qiu Chuchen , Chen Dongjing , Wu You
Published: December 2020

Background

Glioblastoma multiforme (GBM) is a type of high-grade brain tumor known for its proliferative, invasive property, and low survival rate. Recently, with the advancement in therapeutics for tumors such as targeted therapy, individual cancer-specific biomarkers could be recognized as targets for curative purposes. This study identified six differentially expressed genes that have shown significant implications in clinical field, including FPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3. FPR2 was of the same protein family with FPR1, and the latter has been repeatedly reported to promote motility and invasiveness of multiple tumor forms.

Methods

The gene expression profiling of 40 GBM samples and five normal samples from the TCGA database were comprehensively analyzed. The differentially expressed genes (DEGs) were identified using R package and screened by enrichment analysis and examination of protein–protein interaction networks, in order to further explore the functions of DEGs with the highest association with clinical traits and to find hub genes. A qRT-PCR and Western blots were conducted to verify the results of this study.

Results

Our investigation showed that FPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3 were significantly up-regulated in GBM primary tumor compared to the control group. Functional enrichment analysis of the DEGs demonstrated that biological functions related to immune systems, cell division and cell cycle were significantly increased, which were closely related to tumor progression and development. Downstream construction of PPI network analysis indicated that FPR2 was a hub gene involved in high level of interaction with CR3 and VEGFA, which played a key role in inflammatory pathways and cellular dysfunction.

Conclusion

FPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3 were significantly over-expressed in primary tumor samples of GBM patients and were involved in cellular functions and pathways contributing to tumor progression. Out of these six pivotal genes, we intensively focused on FPR2, and our analysis and experimental data both suggested its efficacy as a potential biomarker, serving as an alternative immunotherapeutic target for glioblastoma multiforme.
Curvature of the retroviral capsid assembly is modulated by a molecular switch
Authors: Thames Tyrone , Bryer Alexander J , Qiao Xin , Jeon Jaekyun , Weed Ryan , Janicki Kaylie , Hu Bingwen , Gor’kov Peter L. , Hung Ivan , Gan Zhehong , Perilla Juan R , Chen Bo
Published: December 2020

During the maturation step, the capsid proteins (CAs) of a retrovirus assemble into polymorphic capsids, whose acute curvature is largely determined by insertion of 12 pentamers into the hexameric lattice. Despite years of intensive research, it remains elusive how the CA switches its conformation between the quasi-equivalent pentameric and hexameric assemblies to generate the acute curvature in the capsid. Here we report the high-resolution structural model of the RSV CA T=1 capsid. By comparing with our prior model of the RSV CA tubular assembly consisting entirely of hexameric lattices, we identify that a dozen of residues are the key to dictate the incorporation of acute curvatures in the capsid assembly. They undergo large torsion angle changes, which result a 34° rotation of the C-terminal domain relative to its N-terminal domain around the flexible interdomain linker, without substantial changes of either the conformation of individual domains or the assembly contact interfaces.
Standardization of inducer-activated broad host range expression modules: Debugging and refactoring an alkane-responsive AlkS/PalkBdevice
Authors: Arce-Rodríguez Alejandro , Benedetti Ilaria , Silva-Rocha Rafael , de Lorenzo Víctor
Published: December 2020

Although inducible heterologous expression systems have been available since the birth of recombinant DNA technology, the diversity of devices and genetic architectures of the corresponding vectors have often resulted in a lack of reproducibility and interoperability. In an effort to increase predictability of expression of genes of interest in a variety of possible bacterial hosts we propose a composition standard for debugging and reassembling all regulatory parts that participate in the performance of such devices. As a case study we address then-octane and dicyclopropyl ketone (DCPK)-induciblePalkBpromoter of the alkane biodegradation pOCT plasmid ofPseudomonas putida. The standardized expression module consisted of an editedalkSregulatory gene that is divergently expressed and separated ofPalkBby a synthetic DNA buffer sequence. The native DNA sequence of the structuralalkSgene was modified to alleviate the catabolite repression exerted by some carbon and nitrogen sources through the Crc/Hfq complex of some hosts. ThePalkBpromoter along with thealkSvariants were then formatted as SEVA (Standard European Vector Architecture) cargoes and their activity parameters inP. putidadetermined with GFP and luminiscent reporters. The thereby refactored system showed improvements in various features desirable in conditional expression modules: inducibility, capacity, noise reduction and on/off ratio. When applied to other promoter/regulator pairs, the compositional standard thereby implemented in the AlkS/PalkBmodule will enable more complex genetic programming in non-model bacteria.
Activation of cGAS/STING pathway upon paramyxovirus infection
Authors: Iampietro Mathieu , Dumont Claire , Mathieu Cyrille , Spanier Julia , Robert Jonathan , Charpenay Aude , Dupichaud Sébastien , Dhondt Kévin P. , Aurine Noémie , Pelissier Rodolphe , Ferren Marion , Mély Stéphane , Gerlier Denis , Kalinke Ulrich , Horvat Branka
Published: December 2020

During inflammatory diseases, cancer and infection, the cGAS/STING pathway is known to recognize foreign or self-DNA in the cytosol and activate an innate immune response. Here, we report that negative-strand RNA paramyxoviruses, Nipah virus (NiV) and Measles virus (MeV), can also trigger the cGAS/STING axis. While mice deficient for MyD88, TRIF and MAVS still moderately control NiV infection when compared to WT mice, additional STING deficiency resulted in 100% lethality, suggesting synergistic roles of these pathways in host protection. Moreover, deletion of cGAS or STING resulted in decreased type-I interferon production with enhanced paramyxoviral infection in both human and murine cells. Finally, the phosphorylation and ubiquitination of STING, observed during viral infections, confirmed the activation of cGAS/STING pathway by NiV and MeV. Our data suggest that cGAS/STING activation is critical in controlling paramyxovirus infection, and possibly represent attractive targets to develop countermeasures against severe disease induced by these pathogens.
Systematic evaluation of chromosome conformation capture assays
Authors: Oksuz Betul Akgol , Yang Liyan , Abraham Sameer , Venev Sergey V. , Krietenstein Nils , Parsi Krishna Mohan , Ozadam Hakan , Oomen Marlies E. , Nand Ankita , Mao Hui , Genga Ryan MJ , Maehr Rene , Rando Oliver J. , Mirny Leonid A. , Gibcus Johan Harmen , Dekker Job
Published: December 2020

Chromosome conformation capture (3C)-based assays are used to map chromatin interactions genome-wide. Quantitative analyses of chromatin interaction maps can lead to insights into the spatial organization of chromosomes and the mechanisms by which they fold. A number of protocols such as in situ Hi-C and Micro-C are now widely used and these differ in key experimental parameters including cross-linking chemistry and chromatin fragmentation strategy. To understand how the choice of experimental protocol determines the ability to detect and quantify aspects of chromosome folding we have performed a systematic evaluation of experimental parameters of 3C-based protocols. We find that different protocols capture different 3D genome features with different efficiencies. First, the use of cross-linkers such as DSG in addition to formaldehyde improves signal-to-noise allowing detection of thousands of additional loops and strengthens the compartment signal. Second, fragmenting chromatin to the level of nucleosomes using MNase allows detection of more loops. On the other hand, protocols that generate larger multi-kb fragments produce stronger compartmentalization signals. We confirmed our results for multiple cell types and cell cycle stages. We find that cell type-specific quantitative differences in chromosome folding are not detected or underestimated by some protocols. Based on these insights we developed Hi-C 3.0, a single protocol that can be used to both efficiently detect chromatin loops and to quantify compartmentalization. Finally, this study produced ultra-deeply sequenced reference interaction maps using conventional Hi-C, Micro-C and Hi-C 3.0 for commonly used cell lines in the 4D Nucleome Project.
Road salt compromises functional morphology of larval gills in populations of an amphibian
Authors: Szeligowski Richard V. , Scanley Jules A. , Broadbridge Christine C. , Brady Steven P.
Published: December 2020

Throughout much of the world, winter deicing practices have led to secondary salinization of freshwater habitats, where numerous taxa are vulnerable to elevated salinity. Many amphibians are of particular concern because of their permeable skin and reliance on small ponds and pools, where salinity levels can be high. The early life-history stages of amphibians that develop in these habitats are especially sensitive to salt exposure. Larvae developing in salt-polluted environments must osmoregulate through ion exchange in gills. While salt-induced changes to the physiology of ion exchange in amphibian gills is generally understood, functionally relevant changes in gill morphology remain poorly described. Yet the structure of gills should be an important component affecting their ionoregulatory capacity, for instance in terms available surface area. Larval amphibian gills also play critical roles in gas exchange and foraging. Thus, changes in gill morphology due to salt pollution potentially affect not only osmoregulation, but also respiration and feeding. Here, we used a chronic exposure experiment to quantify the effect of salinity on larval gill morphology in populations of the wood frog (Rana sylvatica). We measured a suite of morphological traits on gill tufts, where ionoregulation and gas exchange occur, and on gill filters, which are used in feeding. Larvae raised in high salinity conditions had gill tufts with lower surface area to volume ratio, while epithelial cells on these tufts were less circular but occurred at higher densities. Gill filters showed increased spacing, which can potentially reduce their efficiency in filtering food particles. Together, these changes seem likely to diminish the ionoregulatory and respiratory capacity of gill tufts, and compromise feeding functionality of gill filters. Thus, a singular change in the aquatic environment from a widespread pollutant has the potential to generate a suite of consequences via changes in gill morphology. Critically, this suite of negative effects is likely most detrimental in salinized environments, where ionoregulatory demands are higher, which in turn should increase respiratory demands along with energy acquisition demands through foraging.

Summary Statement

Chronic road salt exposure alters the functional morphology of gills in larval amphibians, potentially compromising osmoregulation, feeding, and respiration.
IWS1 phosphorylation by AKT3 controls nuclear export of type I IFN mRNAs and sensitivity to oncolytic viral infection, by regulating the alternative RNA splicing of U2AF2
Authors: Laliotis Georgios I. , Kenney Adam D. , Chavdoula Evangelia , Orlacchio Arturo , Kaba Abdul , La Ferlita Alessandro , Anastas Vollter , Tsatsanis Christos , Beane Joal D. , Sehgal Lalit , Coppola Vincenzo , Yount Jacob S. , Tsichlis Philip N.
Published: December 2020

The authors have withdrawn their manuscript. While attempting to reproduce the data on the alternative splicing of exon 2 of U2AF2, they observed that the proposed splicing mechanism could not give rise to a functional U2AF2 protein. In addition, they observed evidence of manipulation in the electropherogram of the splicing junction between exons 1 and 3 and in the primary data on which this electropherogram was based, which were deposited in Mendeley by the first author. These observations raise questions on the integrity of the reported results. In light of this information, the authors have no confidence in the key findings of the paper, and therefore, do not wish it to be cited. If you have any questions, please contact the corresponding author.
Enhancing bioreactor arrays for automated measurements and reactive control with ReacSight
Authors: Bertaux François , Sosa-Carrillo Sebastián , Fraisse Achille , Aditya Chetan , Furstenheim Mariela , Batt Gregory
Published: December 2020

New small-scale, low-cost bioreactors provide researchers with exquisite control of environmental parameters of microbial cultures over long durations, allowing them to perform sophisticated, high-quality quantitative experiments that are particularly useful in systems biology, synthetic biology and bioengineering. However, existing setups are limited in their automated measurement capabilities, primarily because sensitive and specific measurements require bulky, expensive, stand-alone instruments. Here, we present ReacSight, a generic and flexible strategy to enhance bioreactor arrays for automated measurements and reactive experiment control. On the hardware side, ReacSight leverages a pipetting robot for sample collection, handling and loading. On the software side, ReacSight provides a versatile instrument control architecture and a generic event system for reactive experiment control. ReacSight is ideally suited to integrate open-source, open-hardware components but can also accommodate closed-source, GUI-only components (e.g. cytometers). We use ReacSight to assemble a platform for cytometry-based characterization and reactive optogenetic control of parallel yeast continuous cultures. Using a dedicated bioreactor array, we showcase its capabilities on three applications. First, we achieve parallel real-time control of gene expression with light in different bioreactors. Second, we explore the impact of nutrient scarcity on fitness and cellular stress using well-controlled, high-information content competition assays. Third, we exploit nutrient scarcity to achieve dynamic control over the composition of a two-strain consortium. To illustrate the genericity of ReacSight, we also assemble an equivalent platform using the optogenetic-ready, open-hardware and commercially available Chi.Bio bioreactors.
Deciphering colchicine like actions of clerodin in terms of microtubule destabilization based mitotic abnormalities, G2/M-phase arrest, and plant polyploidy
Authors: Roy Sujit , Kundu Lalit Mohan , Roy Gobinda Chandra , Barman Manabendu , Chakraborty Tista , Ghosh Poulomi , Das Ria , Tripathy Debabrata , Singh Nanda , Banerjee Sagnik , Bhattacharjee Atanu , Pal Amit , Chatterjee Anupam , Ray Sanjib
Published: December 2020

Clerodin (C24H34O7), a clerodane diterpenoid, is a bitter principle ofClerodendrum viscosum. The present study aimed to decipher colchicine-like actions of clerodin in terms of microtubule destabilization based mitotic abnormalities, G2-M arrest, and plant polyploidy. Purified clerodin showed increased metaphase frequency in Human Peripheral Blood Lymphocytes (HPBLs), Human Embryonic Kidney cells (HEK-293), andAllium ceparoot apical meristem cells. Both squashed slide of the onion root tip and flow cytometric analysis of radish protoplast revealed a significantly increased frequency of polyploid cells. Flow cytometric analysis showed an increase in frequencies of G2-M in MCF-7 cells from 6.10 to 16.25% after clerodin (200μg/mL) treatment for 24 h. Confocal microscopy imaging of tubulin in clerodin-treated MCF-7 cells revealed microtubule destabilization. Molecular docking and LIGPLOT analysis indicate that clerodin interact in the colchicine binding site, including, single hydrogen bond with Asn 101 of α-tubulin. In summary, our experimental data revealed that clerodin has metaphase arresting, microtubule destabilization, and polyploidy inducing ability similar to colchicine. Molecular docking analysis revealed for the first time that clerodin and colchicine interact at the common site of tubulin residue indicating a common mechanism of action. The results also indicate similar cytotoxic potentialities of both clerodin and colchicine even though they belong to different chemical groups. Thus, clerodin may be used in place of colchicine as a plant polyploidy inducing agent in plant breeding programs in Agriculture.
The effect of corporate social responsibility (CSR) on shareholder value: evidence from the 9/11 terrorist attack
Authors: Ongsakul Viput , Jiraporn Pornsit , Tong Shenghui , Treepongkaruna Sirimon
Published: December 2020

Purpose

This paper aims to explore the effect of corporate social responsibility (CSR) on shareholder value using the stock market reactions to a terrorist attack. This paper exploits the September 11 terrorist attack as an unanticipated exogenous shock that reduced shareholder wealth suddenly and unexpectedly. Based on the risk-mitigation hypothesis, the argument is that more socially responsible firms should suffer less negative market reactions.

Design/methodology/approach

This paper uses the standard event study methodology to estimate the stock market reactions to the 9/11 terrorist attack. Then, the study executes a cross-section analysis to determine whether CSR offers any protection in the presence of a sudden negative shock. Additional analysis includes propensity score matching, instrumental-variable analysis and using Oster’s (2019) method for testing coefficient stability.

Findings

The results show that the negative stock market reactions to the shock are significantly alleviated for firms with strong social responsibility. A rise in CSR by one standard deviation improves the market reactions by 22.56% of the average decline. This is consistent with the prediction of the risk mitigation hypothesis, where CSR spawns moral capital or goodwill that functions as an insurance-like defense in case of an adverse event.

Research limitations/implications

The study focuses on short-term market reactions because this method is more likely to show a causal effect. Future research may investigate long-term effects.

Originality/value

While prior research has investigated the effect of CSR on firm value, it has been challenging to establish causality. The approach is more likely to show causality as it is based on a sudden and unanticipated negative shock. This paper also uses several methods to reduce endogeneity, making it more likely that the results show causality, rather than merely an association.
Distribution of amoebal endosymbiotic environmental chlamydia Neochlamydia S13 via amoebal cytokinesis
Authors: Okude Miho , Matsuo Junji , Yamazaki Tomohiro , Saito Kentaro , Furuta Yoshikazu , Nakamura Shinji , Thapa Jeewan , Okubo Torahiko , Higashi Hideaki , Yamaguchi Hiroyuki
Published: December 2020

We previously isolated a symbiotic environmental amoeba, harboring an environmental chlamydia, Neochlamydia S13. Interestingly, this bacterium failed to survive outside of host cells and was immediately digested inside other amoebae, indicating bacterial distribution via cytokinesis. This may provide a model for understanding organelle development and chlamydial pathogenesis and evolution; therefore, we assessed our hypothesis of Neochlamydia S13 distribution via cytokinesis by comparative analysis with other environmental Chlamydiae (Protochlamydia R18 and Parachlamydia Bn9). Dual staining with 4′,6‐diamidino‐2‐phenylindole and phalloidin revealed that the progeny of Neochlamydia S13 and Protochlamydia R18 existed in both daughter cells with a contractile ring on the verge of separation. However, in contrast to other environmental Chlamydiae, little Neochlamydia S13 16S ribosomal DNA was amplified from the culture supernatant. Interestingly, Neochlamydia S13 failed to infect aposymbiotic amoebae, indicating an intimate interaction with the host cells. Furthermore, its infectious rates in cultures expanded from a single amoeba were always maintained at 100%, indicating distribution via cytokinesis. We concluded that unlike other environmental Chlamydiae, Neochlamydia S13 has a unique ability to divide its progeny only via host amoebal cytokinesis. This may be a suitable model to elucidate the mechanism of cell organelle distribution and of chlamydial pathogenesis and evolution.
Organ‐preserving procedures as an option for treatment of patients with pancreatic neuroendocrine tumours
Authors: Kriger Andrey G. , Berelavichus Stanislav V. , Kaldarov Ayrat R. , Gorin David S. , Raevskaya Marianna B. , Kazennov Vladimir V. , Zekster Vita Y. , Panteleev Vladimir I.
Published: December 2020

Objective

Pancreatic neuroendocrine tumour (pNET) is a rare type of tumour with different malignant potential. Nowadays there is no universal approach for treatment of small and benign‐looking pNETs throughout the world.

Methods

There were 137 patients with pNETs surgically treated in our department between 2007 and 2017. Most of them were female ‐ 96 cases with median age 42 years old. Organ‐preserving procedures (OP) were performed in 44 (32%) cases and were compared with standard procedures 93 (68%) cases.

Results

Main intraoperative characteristics were comparable in groups. There was significantly less estimated blood loss volume in the OP group: less than 1 dL. Postoperative length of stay and drainage placement time were less in the OP group. There were less pancreatic fistulas and no delayed gastric empties in the OP group. 90‐day postoperative mortality rate was the same in both groups: four cases of severe postoperative pancreatitis with acute respiratory distress syndrome.

Conclusion

As the “wait‐and‐see” policy can be not useful due to uncontrolled disease progression, choice of organ‐preserving treatment first can become the first line of decision taking in small benign pNETs. Our experience shows that organ‐preserving treatment is more comfortable for the surgeon and for the patient. However, it is not the universal position. The long‐term survival data still has to be estimated.
COVID‐19 pandemic impact on urology residencies in Asia ‐ An observational study
Authors: Ngoo Kay Seong , Fadzli Ahmad Nazran , Amponin Mark Oliver Christian Sebastian E. , Cho Sung Yong , Chuang Yao‐Chi , Horiguchi Akio , Karthikeyan Vilvapathy Senguttuvan , Morshed Md Selim , Situmorang Gerhard Reinaldi , Tan Tinh Chung , Teoh Jeremy Yuen‐Chun , Thaidumrong Tanet , Ong Teng‐Aik
Published: December 2020

Objective

The Coronavirus Disease 2019 (Covid‐19) pandemic affected surgical training in many ways. This observational study was carried out to evaluate the impact of Covid‐19 on urological residencies across Asia.

Methodology

An open‐ended survey questionnaire examining key areas in a urology training program was distributed to several urologists in Asia. The survey evaluated seven areas including the burden of Covid‐19 disease, the need for re‐deployment of residents, the impact on clinical work, the effect on research work for residents, the delivery of teaching to the residents, the impact on training and assessments, the effects on mental, personal health and social welfare of residents.

Results

Reports from 11 Asian countries were analysed. There is stark variability in Covid‐19 disease burden across Asia. Re‐deployment occurred in selected Asian countries. Affected residents reported challenges obtaining personal protective equipment and training. Clinical workload and research were generally reduced except for countries reporting low volume Covid‐19 cases. Residents teaching evolved from in‐person to online platforms. Almost all residency program postponed their examinations. Mental health disturbance was more pronounced than personal health.

Conclusions

The Covid‐19 pandemic presented multiple obstacles to Asian urology residencies. The understanding of these challenges will assist program directors in developing mitigating measures.
Genome‐wide identification of target genes for transcription factor BR‐C in the silkworm, Bombyx mori
Authors: Guo Meng‐Pei , Qian Wen‐Liang , He Xue‐Chuan , Peng Jian , Wang Peng , Wang Wei‐Na , Xia Qing‐You , Cheng Dao‐Jun
Published: December 2020

Transcription factor Broad Complex (BR‐C) is an ecdysone primary response gene in insects and participates in the regulation of insect growth and development. In this study, we performed a genome‐wide identification of BR‐C target genes in silkworm (Bombyx mori) using chromatin immunoprecipitation followed by high‐throughput sequencing (ChIP‐seq). As a result, a total of 1006 BR‐C ChIP peaks were identified, and 15% of peaks were located in the promoter regions of 133 protein‐coding genes. Functional annotation revealed that these ChIP peak‐associated genes, as potential BR‐C targets, were enriched in pathways related to biosynthetic process, metabolic process, and development. Transcriptome analysis and quantitative real‐time polymerase chain reaction (PCR) examination revealed that developmental changes in expression patterns of a portion of potential BR‐C targets, including HR96 and GC‐α1, were similar to those of BR‐C. ChIP‐PCR examination confirmed that BR‐C could directly bind to the promoters of potential targets. Further, dual luciferase assays demonstrated that HR96 promoter activity was significantly upregulated following BR‐C overexpression, and this upregulation was abolished when the binding motif in the promoter was truncated. This study will be helpful for deciphering the regulatory roles of BR‐C during insect growth and development.
Systematic review of safety and efficacy of belimumab in treating immune‐mediated disorders
Authors: Kaegi Celine , Steiner Urs C. , Wuest Benjamin , Crowley Catherine , Boyman Onur
Published: December 2020

Background

Biologic agents (also termed biologics or biologicals) are becoming increasingly important in the treatment of immune‐mediated diseases. However, the diversity of clinical trials along with the fast pace of publication makes it difficult to determine the level of evidence for the use of a biologic for a given disorder. To address this challenge, we are publishing a series of systematic reviews evaluating the safety and efficacy of B cell–targeting biologics for the treatment of immune‐mediated diseases. In this article, we have assessed the safety and efficacy of belimumab, a fully human IgG1 monoclonal antibody targeting the cytokine B cell–activating factor (BAFF).

Objective

To evaluate belimumab's safety and efficacy for the treatment of immune‐mediated disorders compared to placebo, conventional treatment or other biologics.

Methods

The Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) checklist guided the reporting of the data. We searched the PubMed database between October 4, 2016, and June 23, 2019, concentrating on immune‐mediated disorders.

Results

The literature search identified 583 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 17 articles were finally included in a narrative synthesis.

Conclusions

Belimumab is both safe and effective for the treatment of systemic lupus erythematosus. Results were further promising for the use of belimumab in patients with rheumatoid arthritis and Sjögren’s syndrome. Conversely, results using belimumab in patients with anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis and myasthenia gravis were rather disappointing.
The ties that mobilize us: Networks, intergroup contact, and participation in the Black Lives Matter movement
Authors: Hong Pamela M. , Peoples Clayton D.
Published: December 2020

Scholarship on peoples’ involvement in social movements shows that social networks predict movement participation. Research in this area has traditionally focused on connections to activists—but other kinds of social relationships, such as intergroup contact, may matter as well. In this study, unique data were collected from both a student sample and a general sample of the population to examine how intergroup contact—namely, social ties with African Americans—affects whites’ participation in the Black Lives Matter (BLM) movement. In both samples, intergroup contact is a significant predictor of participation in BLM, net of other factors. The study's findings suggest that social ties outside of activist networks can matter greatly for movement participation; they also suggest that intergroup contact can affect more than just attitudes—it can spur collective action.
Multiculturalism and social cohesion: A Japanese community’s perceptions of “being Australian”
Authors: Funaki Shinsuke , Hamano Takeshi , Phillips Ruth
Published: December 2020

Based on a large‐scale survey conducted with parents from Japanese language schools in Sydney in 2015, this paper aims to review multiple dimensions of social cohesion in the Japanese ethnic community in Australia. Looking at several indices such as economic, political, and cultural integration, the paper describes the social profile of the Japanese ethnic community, questioning the generic perception of the community as a coherent body of middle‐class migrants in Australia. This was achieved through a comparative analysis with outcomes of a national survey of the Australian population on social cohesion and draws attention to the ways in which a particular sense of social cohesion with Australian society is constructed by Japanese migrants. The study found a differentiated sense of belonging to the local community, country of residence (Australia), and nation of origin (Japan). It found communal diversity in the Japanese community resulting from there being a majority of women migrants who were part of cross‐border marriages and their children living in multicultural family circumstances. It was concluded that this configuration within the community leads to advocacy related to a re‐identification as a possible ethnic group of migrants that should be recognized in an inclusive migration settlement policy in Australia.
A spatial Bayesian latent factor model for image‐on‐image regression
Authors: Guo Cui , Kang Jian , Johnson Timothy D.
Published: December 2020

Image‐on‐image regression analysis, using images to predict images, is a challenging task, due to (1) the high dimensionality and (2) the complex spatial dependence structures in image predictors and image outcomes. In this work, we propose a novel image‐on‐image regression model, by extending a spatial Bayesian latent factor model to image data, where low‐dimensional latent factors are adopted to make connections between high‐dimensional image outcomes and image predictors. We assign Gaussian process priors to the spatially varying regression coefficients in the model, which can well capture the complex spatial dependence among image outcomes as well as that among the image predictors. We perform simulation studies to evaluate the out‐of‐sample prediction performance of our method compared with linear regression and voxel‐wise regression methods for different scenarios. The proposed method achieves better prediction accuracy by effectively accounting for the spatial dependence and efficiently reduces image dimensions with latent factors. We apply the proposed method to analysis of multimodal image data in the Human Connectome Project where we predict task‐related contrast maps using subcortical volumetric seed maps.
Incorporation of somatic panels for the detection of haematopoietic transformation in children and young adults with leukaemia predisposition syndromes and with acquired cytopenias
Authors: Noy‐Lotan Sharon , Krasnov Tanya , Dgany Orly , Jeison Marta , Yanir Asaf D. , Gilad Oded , Toledano Helen , Barzilai‐Birenboim Shlomit , Yacobovich Joanne , Izraeli Shai , Tamary Hannah , Steinberg‐Shemer Orna
Published: December 2020

Detection of somatic mutations may help verify the diagnosis of myelodysplastic syndrome (MDS) in patients with persistent cytopenias or with MDS‐predisposition syndromes, prior to the development of overt leukemia. However, the spectrum and consequences of acquired changes in paediatric patients have not been fully evaluated, and especially not in the context of an underlying syndrome. We incorporated a targeted next‐generation‐sequencing panel of 54 genes for the detection of somatic mutations in paediatric and young adult patients with inherited or acquired cytopenias. Sixty‐five patients were included in this study, of whom 17 (26%) had somatic mutations. We detected somatic mutations in 20% of individuals with inherited MDS‐predisposition syndromes, including in patients with severe congenital neutropenia and Fanconi anaemia, and with germline mutations in SAMD9L. Thirty‐eight per cent of children with acquired cytopenias and suspected MDS had somatic changes, most commonly in genes related to signal transduction and transcription. Molecularly abnormal clones often preceded cytogenetic changes. Thus, routine performance of somatic panels can establish the diagnosis of MDS and determine the optimal timing of haematopoietic stem cell transplantation, prior to the development of leukaemia. In addition, performing somatic panels in patients with inherited MDS‐predisposition syndromes may reveal their unique spectrum of acquired mutations.
Debate: Implementation Science can help bridge the gap between evidence and policy – a case study from the Eastern Mediterranean Region
Authors: Rahman Atif , Hamdani Syed Usman
Published: December 2020

The burden from mental disorder in the Eastern Mediterranean Region (EMR) has risen steadily over the last three decades. The unmet need for interventions puts pressure on policymakers for urgent action, often leading to the introduction of programmes developed in high‐income countries, with very little attention to how well these meet local needs. Till well‐designed local research including randomised controlled trials become common practice in low‐ and middle‐income countries, implementation science could provide relatively cheaper and quicker ways of ensuring that these interventions do indeed lead to patient benefit. We present a case study of a teacher‐delivered school mental health intervention developed by international experts, and implemented in the EMR under the auspices of the World Health Organization. We used an implementation research framework to adapt the programme to local needs, obtain stakeholder buy‐in, and design an online‐training programme for rapid dissemination in local schools in Egypt, Iran, Jordan and Pakistan. Within the official roll‐out of the programme in one EMR country (Pakistan), we embedded a hybrid effectiveness‐implementation cluster randomised control trial to evaluate both clinical and implementation outcomes of the adapted intervention. The approach allows for rapid adaptation and evidence building within real‐world implementation settings. Capacity in low‐ and middle‐income countries for such research needs to be developed.
A scoping review of Table 2 fallacy in the oral health literature
Authors: Akinkugbe Aderonke A. , Simon Alyssa M. , Brody Erica R.
Published: December 2020

Background

Coined by Westreich and Greenland in 2013, Table 2 fallacy refers to the practice of reporting estimates of the primary exposure and adjustment covariates derived from a single model on the same table. This study seeks to describe the extent to which Table 2 fallacy is present in the oral health literature and provide recommendations on presenting findings from multivariable‐adjusted models and/or interpretation of adjustment covariate estimates that are not the primary exposure.

Methods

We conducted a scoping review in PubMed and Scopus of human observational studies published in 4 oral health journals (JDR‐CTR, CDOE, JPHD, BMC Oral Health) starting in 2013 until the end of 2018. The resulting articles were exported into Excel and were either included or excluded for full‐text review based on six criteria. After categorizing the articles, we exported and summarized the results in SAS.

Results

A total of 1358 articles were initially screened of which 937 articles were excluded based on title or abstract for being animal studies, systematic reviews or meta‐analysis, prediction models or descriptive studies. The remaining 421 articles were eligible for full text reviewed of which, 189 (45%) committed Table 2 fallacy. The prevalence of table 2 fallacy appears high in the oral health literature.

Conclusions

The problem of presenting multiple effect estimates derived from a single model in the same table is that it inadvertently encourages the reader to interpret all estimates the same way, often as total effects. Implications and recommendations are discussed.
Structural Analogy from a Single Image Pair
Authors: Benaim S. , Mokady R. , Bermano A. , Wolf L.
Published: December 2020

The task of unsupervised image‐to‐image translation has seen substantial advancements in recent years through the use of deep neural networks. Typically, the proposed solutions learn the characterizing distribution of two large, unpaired collections of images, and are able to alter the appearance of a given image, while keeping its geometry intact. In this paper, we explore the capabilities of neural networks to understand image structure given only a single pair of images, and . We seek to generate images that are structurally aligned: that is, to generate an image that keeps the appearance and style of , but has a structural arrangement that corresponds to . The key idea is to map between image patches at different scales. This enables controlling the granularity at which analogies are produced, which determines the conceptual distinction between style and content. In addition to structural alignment, our method can be used to generate high quality imagery in other conditional generation tasks utilizing images and only: guided image synthesis, style and texture transfer, text translation as well as video translation. Our code and additional results are available in https://github.com/rmokady/structural-analogy/
Comparison of voice therapy and selective electrical stimulation of the larynx in early unilateral vocal fold paralysis after thyroid surgery: A retrospective data analysis
Authors: Kurz Annabella , Leonhard Matthias , Denk‐Linnert Doris Maria , Mayr Winfried , Kansy Ines , Schneider‐Stickler Berit
Published: December 2020

Objectives

The goal of the retrospective study was to investigate the 3‐month‐outcome after treatment of patients with early unilateral vocal fold paralysis (UVFP) with either standard voice therapy (VT) or selective electrical stimulation of the larynx (SES).

Design

Non‐randomised retrospective study.

Setting

1519 patients who underwent thyroid surgery between 2015 and 2018 were analysed according vocal fold mobility; UVFP patients were treated either by VT or SES.

Participants

51 UVFP patients.

Main outcome measures

51 UVFP patients have been advised regarding treatment options like either VT (group 1) or SES (group 2). The patients of group 1 (n = 26) and 2 (n = 25) were re‐assessed up to 3 months post‐operatively regarding UVFP persistence/recovery and perceptive voice sound quality. At follow‐ups, perceptual analysis of voice sound (using roughness=R/breathiness=B/hoarseness=H scale) and endoscopic laryngoscopy have been performed. Position of immobile vocal fold, shape of glottal closure and RBH parameters have been considered for statistical analyses.

Results

Restitution of UVFP with regular respiratory vocal fold mobility of both vocal folds occurred in 53.8% of group 1 (VT), and in 40.0% of group 2 (SES) after 3 months of therapy between both groups. No difference could be seen for RBH, type of glottal closure and position of ailing vocal folds in patients with persisting UVFP within both groups and between the groups.

Conclusions

The study reveals that SES can achieve similar functional outcome in early UVFP. Thus, it should be considered as an equivalent therapy alternative to VT for treatment of early UVFP patients since no significant difference in vocal outcome and glottal configuration between the two groups could be demonstrated.
Lichen aureus with pseudolymphomatous infiltrate
Authors: Kolm Isabel , Buset Caroline , Flury Ursula , Nosek Daniel , Kazakov Dmitry V. , Kempf Werner
Published: December 2020

Lichen aureus is a variant of pigmented purpuric dermatoses. The usual histopathology of lichen aureus is characterized by a subepidermal dense, band‐like lymphocytic infiltrate, extravasated erythrocytes, and hemosiderin deposits. We report three patients with lichen aureus on the extremities with similar clinical, dermoscopic, and histopathological findings characterized by a dense band‐like relatively deep dermal infiltrate accompanied by extravasation of erythrocytes and hemosiderin deposits occasioning a resemblance to a lymphoproliferative disorder.
Changes in landscape‐scale tree biodiversity in the north‐eastern USA since European settlement
Authors: Vellend Mark , Thompson Jonathan R. , Danneyrolles Victor , Rousseu François
Published: December 2020

Aim

Despite global biodiversity losses, trends at local and regional scales are context dependent. Recent studies have been criticized for lacking baselines preceding human impacts, and few such studies have addressed the landscape scale. Our aim was to quantify temporal trends in landscape‐scale tree diversity during an unambiguous period of massively increased anthropogenic disturbance and to test the hypothesis that land use can increase landscape‐scale diversity via increased environmental heterogeneity.

Location

Eastern USA.

Time period

1620–2008.

Major taxa studied

Trees.

Methods

We combined data from archival land surveys and modern‐day forest inventories in the north‐eastern USA to quantify tree genus diversity at the scale of towns (“landscapes”). We modelled change in diversity over time as a function of the proportion of the landscape historically converted to agriculture, historical temperature increases and nitrogen deposition, and other abiotic and spatial variables. We also tested for scale‐dependent changes in beta diversity.

Results

Overall, tree genus diversity (Shannon and Simpson indices) changed minimally over time on average, but the magnitude of change increased with the maximum historical percentage of the town in agriculture. Other predictor variables had minimal influence. Beta diversity increased over time for nearby pairs of towns and decreased over time for more distant towns.

Main conclusions

Forests have regrown on much former agricultural land, and our results support the hypothesis that increased landscape‐scale environmental heterogeneity, attributable to land use, increased tree diversity. Where agricultural land use was uncommon, declines in diversity might be attributable to effects of logging and fire suppression. Even the strongest driver of biodiversity loss at local and global scales (human land use) can lead to increases in biodiversity at the landscape scale, in addition to scale dependence of biotic differentiation versus homogenization.
Immune deficiency is a risk factor for severe COVID‐19 in people living with HIV
Authors: Hoffmann Christian , Casado José L. , Härter Georg , Vizcarra Pilar , Moreno Ana , Cattaneo Dario , Meraviglia Paola , Spinner Christoph D. , Schabaz Farhad , Grunwald Stephan , Gervasoni Cristina
Published: December 2020

Objectives

A prior T cell depletion induced by HIV infection may carry deleterious consequences in the current COVID‐19 pandemic. Clinical data on patients co‐infected with HIV and SARS‐CoV‐2 are still scarce.

Methods

This multicentre cohort study evaluated risk factors for morbidity and mortality of COVID‐19 in people living with HIV (PLWH), infected with SARS‐CoV‐2 in three countries in different clinical settings. COVID‐19 was clinically classified as to be mild‐to‐moderate or severe.

Results

Of 175 patients, 49 (28%) had severe COVID‐19 and 7 (4%) patients died. Almost all patients were on antiretroviral therapy (ART) and in 94%, HIV RNA was below 50 copies/mL prior to COVID‐19 diagnosis. In the univariate analysis, an age 50 years or older, a CD4+ T cell nadir of < 200/µl, current CD4+ T cells < 350/µl and the presence of at least one comorbidity were significantly associated with severity of COVID‐19. No significant association was found for gender, ethnicity, obesity, a detectable HIV RNA, a prior AIDS‐defining illness, or tenofovir (which was mainly given as alafenamide) or protease inhibitor use in the current ART. In a multivariate analysis, the only factor associated with risk for severe COVID‐19 was a current CD4+ T cell count of < 350/µl (adjusted odds ratio 2.85, 95% confidence interval 1.26‐6.44, p=0.01). The only factor associated with mortality was a low CD4 T cell nadir.

Conclusions

In PLWH, immune deficiency is a possible risk factor for severe COVID‐19, even in the setting of virological suppression. There is no evidence for a protective effect of PIs or tenofovir alafenamide.