bluuebunny/crossref_metadata_2025 huggingface dataset:
Soldiership, Christianity, and the Crimean War: The Reception of Catherine Marsh’s Memorials of Captain Hedley Vicars
Authors: Spanou Petros
Published: January 2022

Recent scholarship has done much to illuminate the cultural significance of Catherine Marsh’s popular evangelical biography of Hedley Vicars, a British officer killed during the Crimean War (1853–1856). However, scholars have not systematically examined the ways in which Marsh’s hagiographical portrait of this officer – who, in the eyes of many contemporaries, was the epitome of the ‘Christian soldier’ – was drawn into religious debates following its publication in December 1855. A crucial part of its reception history thus remains incomplete. Building on secondary literature which has recently opened new avenues for the fruitful investigation of the interface between religion and war in Victorian culture, and employing hitherto untapped sources, this article advances fresh perspectives on the place of Vicars’s ‘Christian soldiership’ in wartime religious thought. The article situates Marsh’s Memorials of Captain Hedley Vicars within the context of debates on the lawfulness of war for Christians in general, and on the justice of the Crimean War in particular, before tracing the deployment of the religious and heroic themes of the Memorials by pro-war clergy against peace advocates. The article then explores the peace movement’s critiques of Marsh’s Memorials which sought to undercut the idea of the ‘Christian soldier’ and to demolish the argument that Vicars’s martial valour and fervent piety affirmed the compatibility of war, soldiering, and Christianity. The result is an account which demonstrates the centrality of religious debate to contemporary understandings of a war which helped to define the Victorian era.
Risk of adrenal insufficiency in patients with polymyalgia rheumatica versus patients with rheumatoid arthritis: A cross-sectional study
Authors: Kasahara Akiko , Kida Takashi , Hirano Aiko , Omura Satoshi , Sofue Hideaki , Sakashita Aki , Sagawa Tomoya , Asano Mai , Fukui Michiaki , Wada Makoto , Kohno Masataka , Kawahito Yutaka
Published: January 2022

Objective

To determine whether patients with polymyalgia rheumatica (PMR) are more susceptible to glucocorticoid-induced adrenal insufficiency, one of the barriers to glucocorticoid tapering strategies, compared to patients with rheumatoid arthritis (RA).

Methods

This cross-sectional study included PMR and RA patients who underwent adrenocorticotropic hormone (ACTH) tests to assess adrenal function. The eligibility criteria were as follows: previous use of prednisolone (PSL) ≥ 5 mg/day, use of PSL for six consecutive months before ACTH test, and current use of PSL at 5 mg/day or less. The association between disease type (PMR vs. RA) and insufficient adrenal response was assessed using logistic regression models.

Results

Twenty-six of 34 (76.5%) patients with PMR and 13 of 37 (35.1%) patients with RA had insufficient adrenal response. Compared to patients with RA, patients with PMR were more likely to have insufficient adrenal response, even after adjusting for age, sex, and PSL dose (adjusted odds ratio, 6.75; 95% confidence interval, 1.78–25.60).

Conclusion

Patients with PMR have a higher risk of glucocorticoid-induced adrenal insufficiency than patients with RA. Assessing the adrenal function in patients with PMR will contribute to establishing a more appropriate glucocorticoid reduction strategy.
Thrombosis-associated hypofibrinogenemia: novel abnormal fibrinogen variant FGG c.8G>A with oxidative posttranslational modifications
Authors: Ceznerová Eliška , Kaufmanová Jiřina , Stikarová Jana , Pastva Ondřej , Loužil Jan , Chrastinová Leona , Suttnar Jiři , Kotlín Roman , Dyr Jan Evangelista
Published: January 2022

Here, we present the first case of fibrinogen variant FGG c.8G>A. We investigated the behaviour of this mutated fibrinogen in blood coagulation using fibrin polymerization, fibrinolysis, fibrinopeptides release measurement, mass spectrometry (MS), and scanning electron microscopy (SEM). The case was identified by routine coagulation testing of a 34-year-old man diagnosed with thrombosis. Initial genetic analysis revealed a heterozygous mutation in exon 1 of the FGG gene encoding gamma chain signal peptide. Fibrin polymerization by thrombin and reptilase showed the normal formation of the fibrin clot. However, maximal absorbance within polymerization was lower and fibrinolysis had a longer degradation phase than healthy control. SEM revealed a significant difference in clot structure of the patient, and interestingly, MS detected several posttranslational oxidations of fibrinogen. The data suggest that the mutation FGG c.8G>A with the combination of the effect of posttranslational modifications causes a novel case of hypofibrinogenemia associated with thrombosis.
MicroRNAs in Pancreatic Cancer and Chemoresistance
Authors: Pan Yue , Li Kun , Tao Xufeng , Li Ning , Huang Jing , Liu Jianzhou , Xiao Gary Guishan
Published: January 2022

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading malignancies affecting human health, largely because of the development of resistance to chemotherapy/radiotherapy. There are many mechanisms that mediate the development of drug resistance, such as the transport of antineoplastic agents into cells, shifts in energy metabolism and environment, antineoplastic agent-induced DNA damage, and genetic mutations. MicroRNAs are short, noncoding RNAs that are 20 to 24 nucleotides in length and serve several biological functions. They bind to the 3′-untranslated regions of target genes and induce target degradation or translational inhibition. MicroRNAs can regulate several target genes and mediate PDAC chemotherapy/radiotherapy resistance. The detection of novel microRNAs would not only reveal the molecular mechanisms of PDAC and resistance to chemotherapy/radiotherapy but also provide new approaches to PDAC therapy. MicroRNAs are thus potential therapeutic targets for PDAC and might be essential in uncovering new mechanisms of the disease.
Facility Type Affects Treatment Outcomes for Patients With Mucinous Cystic Neoplasms and Intraductal Papillary Mucinous Neoplasms of the Pancreas
Authors: Ahmad Maria , Maegawa Felipe B. , Ashouri Yazan , Le Emily , Mendoza Ladd Antonio , Elhanafi Sherif , Philipovskiy Alexander , Tyroch Alan H. , Konstantinidis Ioannis T.
Published: January 2022

Objective

Academic centers report better outcomes for pancreatic ductal adenocarcinoma. We hypothesized that treatment outcomes for mucinous cysts differ according to institution type.

Methods

Using the National Cancer Data Base, we analyzed data on patients with mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs).

Results

Of 3278 identified patients, 2622 (80%) had IPMNs and 656 (20%) had MCNs. While most academic/research programs (ARCPs, 84.9%) treated more than 10 patients/year, this was true for only 59% of integrated network cancer programs, 37.3% of comprehensive community cancer programs, and 0% of community cancer programs (P < 0.001). Surgery was used more often in ARCPs and for smaller tumors. The ARCPs had higher rates of margin negative resections with retrieval of 15 or more nodes with the lowest 30- and 90-day mortality rates. The median overall survival was better in ARCPs (110.3 months) than comprehensive community cancer programs (75.1 mo), community cancer programs (75.1 mo), or integrated network cancer programs (100.8 mo, P < 0.001).

Conclusions

Treatment of MCNs and IPMNs of the pancreas at academic centers is associated with a higher probability of pancreatectomy, disease identification in a noninvasive stage, and better overall survival. Centralization of care for mucinous pancreatic cysts will lead to improved outcomes.
Perceptions of Experiences of Recovery After Pancreaticoduodenectomy—A Phenomenographic Interview Study
Authors: Andersson Thomas K. , Engström My , Bjerså Kristofer
Published: January 2022

Background

Pancreatic surgery in the context of enhanced recovery has mainly been evaluated using clinical variables. However, there is limited knowledge about patients’ perceptions of recovery in this context. Hence, the aim of this study was to explore patients’ perceptions of recovery after pancreatic surgery within an enhanced recovery program.

Objective

To explore the variations in patients’ perceptions, a qualitatively designed study was undertaken.

Methods

Data in this phenomenographic study consisted of interviews with 19 patients at 4 to 6 weeks after surgery.

Results

Recovery after pancreatic surgery was classified into 5 categories, based on patients’ perceptions: to be as before, affected by symptoms, physical activity, understanding the process, and facilitated by other people.

Conclusion

The study focused on various areas of recovery, which took place between the in-hospital and after-discharge phases. Physical experiences were found to disturb recovery, in contrast to social and emotional experiences, which facilitated recovery. Variations in perceptions of recovery suggest that care may need to be more individualized, both in the preoperative and the postoperative phase. Working with realistic expectations and early patient education might better prepare patients to continue working on their own recovery after discharge from the hospital.

Implications for Practice

Major cancer surgery needs to be perceived as a personal journey for the patient, even in enhanced recovery program care. Preoperative education is good, but adding continuous and individually adopted education during recovery is better. Knowledge about both hindering and facilitating factors for recovery is important for the healthcare personal.
New Suturing Approaches for Patients with Nasal Hump and Septal Deviation
Authors: Öztürk Güncel
Published: January 2022

Rhinoplasty is one of the most common applied aesthetic surgery procedures worldwide. Dorsal hump deformity is common in western countries due to nasal profile of Whites. Septal deviation deformity is another common problem among patients who goes through aesthetic and plastic surgery. The estimated rate of septal deviation was reported to be 77% to 90% in the general population. The patients who had dorsal hump and septal deviation simultaneously are considered to be challenging for surgeons. In this research, the author presents new suturing approaches, which would be beneficial in dorsal preservation techniques in terms of fixing the septal deviation. One hundred and seventeen patients met the inclusion and exclusion criteria, and their records were assessed retrospectively. The patients who underwent either push-down and let-down techniques or septorhinoplasty were applied “8” shaped or loop suturing approaches. In addition, 33 patients with the same inclusion and exclusion criteria in whom classical loop suturing technique was used were included in the study. The Rhinoplasty Outcome Evaluation scores ranged between 80 and 100 points after 1 year. The initial median Rhinoplasty Outcome Evaluation score was 52.5, and it increased to 91.00 points at 12 months after surgery (P < 0.001). Patient satisfaction was excellent in 92.68% of the study group, and it was 72.72% in the control group. Excellent satisfaction rate was higher in the study group (P = 0.01). This study is the first to demonstrate the beneficial effects of loop and “8”-shaped sutures in patients who had nasal hump and septal deviation deformities. These suturing approaches will allow better long-term outcomes.
Tuftsin: a natural molecule against SARS-CoV-2 infection
Authors: Huang Jiahao , Wang Jing , Wang Ziyuan , Chu Ming , Wang Yuedan
Published: January 2022

Coronavirus disease 2019 (COVID-19) continuously proceeds despite the application of a variety of vaccines. It is still urgent to find effective ways to treat COVID-19. Recent studies indicate that NRP1, an important receptor of the natural peptide tuftsin, facilitates SARS-CoV-2 infection. Importantly, tuftsin is a natural human molecule released from IgG. Here, we found 91 overlapping genes between tuftsin targets and COVID-19-associated genes. Bioinformatics analyses indicated that tuftsin could also target ACE2 and exert some immune-related functions to treat COVID-19. Using surface plasmon resonance (SPR) analysis, we confirmed that tuftsin can bind ACE2 and NRP1 directly. Moreover, tuftsin effectively impairs the binding of SARS-CoV-2 S1 to ACE2. Thus, tuftsin is an attractive drug against COVID-19. And tuftsin as natural immunostimulating peptide in human, we speculate that tuftsin may has crucial roles in asymptomatic carriers or mild cases of COVID-19.
Increased airborne transmission of COVID-19 with new variants, Implications for health policies
Authors: Rowe Bertrand.R. , Canosa André , Meslem Amina , Rowe Frantz
Published: January 2022

New COVID-19 variants, either of higher viral load such as delta or higher contagiousness like omicron, can lead to higher airborne transmission than historical strains. This paper highlights their implications for health policies, based on a clear analytical understanding and modeling of the airborne contamination paths, of the dose following exposure, and the importance of the counting unit for pathogens, itself linked to the dose-response law. Using the counting unit of Wells, i.e. the quantum of contagium, we develop the conservation equation of quanta which allows deriving the value of the quantum concentration at steady state for a well-mixed room. The link with the monitoring concentration of carbon dioxide is made and used for a risk analysis of a variety of situations for which we collected CO2time-series observations. The main conclusions of these observations are that 1) the present norms of ventilation, are both insufficient and not respected, especially in a variety of public premises, leading to high risk of contamination and that 2) air can often be considered well-mixed. Finally, we insist that public health policy in the field of airborne transmission should be based on a multi parameter analysis such as the time of exposure, the quantum production rate, mask wearing and the infector proportion in the population in order to evaluate the risk, considering the whole complexity of dose evaluation. Recognizing airborne transmission requires thinking in terms of time of exposure rather than in terms of proximal distance.

Highlights

Relative airborne risk assessment following variant viral load and contagiousness

Indoor analytical risk assessment including absence of ventilation

Adequacy of the present norms of ventilation to Covid-19 pandemic

Observation of non-compliance to standards concerning CO2Indoor Air Quality
Limited Cross-Variant Immunity after Infection with the SARS-CoV-2 Omicron Variant Without Vaccination
Authors: Suryawanshi Rahul K. , Chen Irene P , Ma Tongcui , Syed Abdullah M. , Brazer Noah , Saldhi Prachi , Simoneau Camille R , Ciling Alison , Khalid Mir M. , Sreekumar Bharath , Chen Pei-Yi , Kumar G. Renuka , Montano Mauricio , Garcia-Knight Miguel A , Sotomayor-Gonzalez Alicia , Servellita Venice , Gliwa Amelia , Nguyen Jenny , Silva Ines , Milbes Bilal , Kojima Noah , Hess Victoria , Shacreaw Maria , Lopez Lauren , Brobeck Matthew , Turner Fred , Soveg Frank W , George Ashley F. , Fang Xiaohui , Maishan Mazharul , Matthay Michael , Greene Warner C. , Andino Raul , Spraggon Lee , Roan Nadia R. , Chiu Charles Y. , Doudna Jennifer , Ott Melanie
Published: January 2022

SARS-CoV-2 Delta and Omicron strains are the most globally relevant variants of concern (VOCs). While individuals infected with Delta are at risk to develop severe lung disease1, Omicron infection causes less severe disease, mostly upper respiratory symptoms2,3. The question arises whether rampant spread of Omicron could lead to mass immunization, accelerating the end of the pandemic. Here we show that infection with Delta, but not Omicron, induces broad immunity in mice. While sera from Omicron-infected mice only neutralize Omicron, sera from Delta-infected mice are broadly effective against Delta and other VOCs, including Omicron. This is not observed with the WA1 ancestral strain, although both WA1 and Delta elicited a highly pro-inflammatory cytokine response and replicated to similar titers in the respiratory tracts and lungs of infected mice as well as in human airway organoids. Pulmonary viral replication, pro-inflammatory cytokine expression, and overall disease progression are markedly reduced with Omicron infection. Analysis of human sera from Omicron and Delta breakthrough cases reveals effective cross-variant neutralization induced by both viruses in vaccinated individuals. Together, our results indicate that Omicron infection enhances preexisting immunity elicited by vaccines, but on its own may not induce broad, cross-neutralizing humoral immunity in unvaccinated individuals.
Sparse and Skew Hashing of K-Mers
Authors: Pibiri Giulio Ermanno
Published: January 2022

Motivation

A dictionary of k-mers is a data structure that stores a set of n distinct k-mers and supports membership queries. This data structure is at the hearth of many important tasks in computational biology. High-throughput sequencing of DNA can produce very large k-mer sets, in the size of billions of strings – in such cases, the memory consumption and query efficiency of the data structure is a concrete challenge.

Results

To tackle this problem, we describe a compressed and associative dictionary for k-mers, that is: a data structure where strings are represented in compact form and each of them is associated to a unique integer identifier in the range [0, n). We show that some statistical properties of k-mer minimizers can be exploited by minimal perfect hashing to substantially improve the space/time trade-off of the dictionary compared to the best-known solutions.

Availability

The C++ implementation of the dictionary is available at https://github.com/jermp/sshash.

Contact

giulio.ermanno.pibiri@isti.cnr.it
Hidden multiplicity in the analysis of variance (ANOVA): multiple contrast tests as an alternative
Authors: Hothorn Ludwig A.
Published: January 2022

In bio-medical studies, the p-values of the F-tests in ANOVA are usually interpreted independently as measures of the significance of the associated factors. This ’hidden multiplicity’ effect increases the false positive rate. Therefore, Cramer et al. (2016) proposed the Bonferroni adjustment of the p-values to control for familywise error rate for the experiment. Here, instead of using F-tests, it is alternatively suggested to use multiple contrast tests vs. total mean and to perform multiplicity adjustment by object merging in the interplay between the R-packages emmeans and multcomp. This new approach, denotes as multipleANOM, allows not only to interpret global factor effects but also local effects between factor levels as adjusted p-values or simultaneous confidence intervals for selected effect measures in generalized linear models. R-code is provided by means of selected data examples.
Dietary butyrate treatment enhances healthy metabolites by longitudinal untargeted metabolomic analysis in amyotrophic lateral sclerosis mice
Authors: Ogbu Destiny , Zhang Yongguo , Claud Katerina , Xia Yinglin , Sun Jun
Published: January 2022

Microbial metabolites affect the neuron system and muscle cell functions. Amyotrophic Lateral Sclerosis (ALS) is a multifactorial neuromuscular disease. Our previous study has demonstrated elevated intestinal inflammation and dysfunctional microbiome in ALS patients and an ALS mouse model (human-SOD1G93Atransgenic mice). However, the metabolites in ALS progression are unknown. Using an unbiased global metabolomic measurement and targeted measurement, we investigated the longitudinal changes of fecal metabolites in the SOD1G93Amice over the course of 13 weeks. We compared the changes of metabolites and inflammatory response in age-matched WT and SOD1G93Amice treated with bacterial product butyrate. We found changes in carbohydrate levels, amino acid metabolism, and formation of gamma-glutamyl amino acids. Shifts in several microbially-contributed catabolites of aromatic amino acids agree with butyrate-induced changes in composition of gut microbiome. Declines in gamma-glutamyl amino acids in feces may stem from differential expression of GGT in response to butyrate administration. Due to signaling nature of amino acid-derived metabolites, these changes indicate changes in inflammation (e.g. histamine) and contribute to differences in systemic levels of neurotransmitters (e.g. GABA, glutamate). Butyrate treatment was able to restore some of the healthy metabolites in ALS mice. Moreover, microglia in the spinal cord were measured by the IBA1 staining. Butyrate treatment significantly suppressed the IBA1 level in the SOD1G93Amice. The serum IL-17 and LPS were significantly reduced in the butyrate treated SOD1G93Amice. We have demonstrated an inter-organ communications link among metabolites, inflammation, and ALS progression, suggesting the potential to use metabolites as ALS hallmarks and for treatment.

Graphic Abstract

We compared the changes of metabolites and inflammatory response in age-matched WT and SOD1G93Amice treated with bacterial product butyrate. Butyrate treatment was able to restore some of the healthy metabolites in ALS mice. Due to signaling nature of amino acid-derived metabolites, these changes indicate changes in inflammation and contribute to differences in systemic levels of neurotransmitters (e.g. GABA, glutamate). Moreover, butyrate treatment significantly suppressed the microglia IBA1 level and aggregated SOD1G93Ain the SOD1G93Amice. The inflammatory cytokine, e.g serum IL-17, was significantly reduced in the butyrate treated SOD1G93Amice. We have demonstrated an inter-organ communications link among metabolites, inflammation, and ALS progression, suggesting the potential to use metabolites as ALS hallmarks and for treatment.
Analog of the Hutchinson equation in biophysical neurodynamics: from the Morris-Lecar model to a delay differential equation
Authors: Paraskevov Alexander
Published: January 2022

Starting with the classical biophysical Morris-Lecar model of neuronal excitability, we introduce a functional analog of the Hutchinson equation initially obtained for population dynamics with delayed negative feedback. It is shown that the resulting equation with a fixed time delay qualitatively reproduces the dynamics of the original model upon direct current stimulation, preserving both the initial type of neuronal excitability and biophysically realistic spike shape within a wide range of the delay values. If the delay becomes very small (2 ms or less), the simplified delay-based model exhibits a distinct transition from the 1st to the 2nd excitability type.
Single-sequence protein structure prediction using supervised transformer protein language models
Authors: Wang Wenkai , Peng Zhenling , Yang Jianyi
Published: January 2022

It remains challenging for single-sequence protein structure prediction with AlphaFold2 and other deep learning methods. In this work, we introduce trRosettaX-Single, a novel algorithm for singlesequence protein structure prediction. It is built on sequence embedding from s-ESM-1b, a supervised transformer protein language model optimized from the pre-trained model ESM-1b. The sequence embedding is fed into a multi-scale network with knowledge distillation to predict inter-residue 2D geometry, including distance and orientations. The predicted 2D geometry is then used to reconstruct 3D structure models based on energy minimization. Benchmark tests show that trRosettaX-Single outperforms AlphaFold2 and RoseTTAFold on natural proteins. For instance, with single-sequence input, trRosettaX-Single generates structure models with an average TM-score ~0.5 on 77 CASP14 domains, significantly higher than AlphaFold2 (0.35) and RoseTTAFold (0.34). Further test on 101 human-designed proteins indicates that trRosettaX-Single works very well, with accuracy (average TM-score 0.77) approaching AlphaFold2 and higher than RoseTTAFold, but using much less computing resource. On 2000 designed proteins from network hallucination, trRosettaX-Single generates structure models highly consistent to the hallucinated ones. These data suggest that trRosettaX-Single may find immediate applications in de novo protein design and related studies. trRosettaX-Single is available through the trRosetta server at: http://yanglab.nankai.edu.cn/trRosetta/.
Live-cell fluorescence lifetime multiplexing using synthetic fluorescent probes
Authors: Frei Michelle S. , Koch Birgit , Hiblot Julien , Johnsson Kai
Published: January 2022

Fluorescence lifetime multiplexing requires fluorescent probes with distinct fluorescence lifetimes but similar spectral properties. Even though synthetic probes for many cellular targets are available for multicolor live-cell fluorescence microscopy, few of them have been characterized for their use in fluorescence lifetime multiplexing. Here we demonstrate that from a panel of 18 synthetic probes, eight pairwise combinations are suitable for fluorescence lifetime multiplexing in living mammalian cell lines. Moreover, combining multiple pairs in different spectral channels enables us to image up to six different biological targets, effectively doubling the number of observable targets. The combination of synthetic probes with fluorescence lifetime multiplexing is thus a powerful approach for live-cell imaging.
Phylovar: Towards scalable phylogeny-aware inference of single-nucleotide variations from single-cell DNA sequencing data
Authors: Edrisi Mohammadamin , Valecha Monica V. , Chowdary Sunkara B. V. , Robledo Sergio , Ogilvie Huw A. , Posada David , Zafar Hamim , Nakhleh Luay
Published: January 2022

Single-nucleotide variants (SNVs) are the most common variations in the human genome. Recently developed methods for SNV detection from single-cell DNA sequencing (scDNAseq) data, such as SCIΦ and scVILP, leverage the evolutionary history of the cells to overcome the technical errors associated with single-cell sequencing protocols. Despite being accurate, these methods are not scalable to the extensive genomic breadth of single-cell whole-genome (scWGS) and whole-exome sequencing (scWES) data.

Here we report on a new scalable method, Phylovar, which extends the phylogeny-guided variant calling approach to sequencing datasets containing millions of loci. Through benchmarking on simulated datasets under different settings, we show that, Phylovar outperforms SCIΦ in terms of running time while being more accurate than Monovar (which is not phylogeny-aware) in terms of SNV detection. Furthermore, we applied Phylovar to two real biological datasets: an scWES triple-negative breast cancer data consisting of 32 cells and 3375 loci as well as an scWGS data of neuron cells from a normal human brain containing 16 cells and approximately 2.5 million loci. For the cancer data, Phylovar detected somatic SNVs with high or moderate functional impact that were also supported by bulk sequencing dataset and for the neuron dataset, Phylovar identified 5745 SNVs with non-synonymous effects some of which were associated with neurodegenerative diseases. We implemented Phylovar and made it publicly available athttps://github.com/mae6/Phylovar.git.
RT-qPCR as a screening platform for mutational and small molecule impacts on structural stability of RNA tertiary structures
Authors: Zafferani Martina , Muralidharan Dhanasheel , Hargrove Amanda E.
Published: January 2022

The exponential increase in the discovery and characterization of RNA tertiary structures has highlighted their active role in a variety of human disease, yet often their interactome and specific function remain unknown. Small molecules offer opportunities to both decode these cellular roles and develop therapeutics, yet there are few examples of small molecules that target biologically relevant RNA tertiary structures. While RNA triple helices are a particular attractive target, discovery of triple helix modulators has been hindered by the lack of correlation between small molecule affinity and effect on structural modulation, thereby limiting the utility of affinity-based screening as a primary filtering method. To address this challenge, we developed a high-throughput RT-qPCR screening platform that reports on the effect of mutations and additives, such as small molecules, on the structuredness of triple helices. Using the 3’-end of the oncogenic non-coding RNA MALAT1 as an example, we demonstrated the applicability of both a two-step and a one-pot method to assess the impact of mutations and small molecules on the stability of the triple helix. Employment of a functional high-throughput assay as a primary screen will significantly expedite the discovery of probes that modulate RNA triple helices structural landscape and, consequently, help gain insight into the roles of these pervasive structures.
Conserved Untranslated Regions of Multipartite Viruses: Natural Markers of Novel Viral Genomic Components and Tags of Viral Evolution
Authors: Zhang Song , Yang Caixia , Wu Jiaxing , Qiu Yuanjian , Xuan Zhiyou , Yang Liu , Liao Ruiling , Liang Xiaofei , Yu Haodong , Ren Fang , Dong Yafeng , Xie Xiaoying , Han Yanhong , Wu Di , Ramos-González Pedro Luis , Freitas-Astúa Juliana , Zhou Changyong , Cao Mengji
Published: January 2022

Viruses with split genomes are categorized as being either segmented or multipartite according to whether their genomic segments occur in single or different virions. Some complexity will exist, in that inherited “core” vital segments viruses may renew the others once host and environmental alterations keep driving viral evolution. Despite this uncertainty, empirical observations have been made across the split genomes in the untranslated regions (UTRs) on the short or long stretches of conserved or identical sequences. In this study, we describe a methodology that combines RNA and small RNA sequencing, conventional BLASTx, and iterative BLASTn of UTRs to detect viral genomic components even if they encode orphan genes (ORFans). Within the phylum Kitrinoviricota, novel putative multipartite viruses and viral genomic components were annotated using data obtained from our sampling or publicly available sources. The novel viruses, as extensions or intermediate nodes, enriched the information of the evolutionary networks. Furthermore, the diversity of novel genomic components emphasized the evolutionary roles of reassortment and recombination, as well as genetic deletion, strongly supporting the genomic complexity. These data also suggest insufficient knowledge of these genomic components for categorizing some extant viral taxa. The relative conservation of UTRs at the genome level may explain the relationships between monopartite and multipartite viruses and how the multipartite viruses can have a life strategy involving multiple host cells.

Author summary

The current workflows for virus identification are largely based on high-throughput sequencing and coupled protein sequence homology-dependent analysis methods and tools. However, for viruses with split genomes, the identification of genomic components whose deduced protein sequences are not homologous to known sequences is inadequate. Furthermore, many plant-infecting multipartite viruses contain conserved UTRs across their genomic components. Based on this, we propose a practical method of UTR-backed iterative BLASTn (UTR-iBLASTn) to explore the components with ORFans and study virus evolution using the UTRs as signals. These shed light on viral “dark matter”—unknown/omitted genomic components of segmented/multipartite viruses from different kingdoms and hosts, and the origins of these components.
Comparative study of the unbinding process of some HTLV-1 protease inhibitors using Unbiased Molecular Dynamics simulation
Authors: Tiyoula Fereshteh Noroozi , Aryapour Hassan , Moghadam Mostafa Javaheri
Published: January 2022

The HTLV-1 protease is one of the major antiviral targets to overwhelm this virus. Several research groups have been developing protease inhibitors over the years, but none has been successful. In this regard, the development of new HTLV-1 protease inhibitors based on fixing the defects of previous inhibitors will overcome the absence of curative treatment for this oncovirus. Thus, we decided to study the unbinding pathways of the most potent (compound 10, Ki = 15 nM) and one of the weakest (compound 9, Ki = 7900 nM) protease inhibitors, which are very structurally similar, with the PDB IDs: 4YDG, 4YDF, using the Supervised Molecular Dynamics (SuMD) method. In this project, we had various short and long-time-scale simulations, that in total, we could have 12 successful unbindings (a total of 14.8 μs) for the two compounds in both mp forms. This comparative study measured all the essential factors simultaneously in two different inhibitors, which improved our results. This study revealed that Asp32 or Asp32′ in the two forms of mp state similarly exert super power effects on maintaining both potent and weak inhibitors in the binding pocket of HTLV-1 protease. In parallel with the important impact of these two residues, in the potent inhibitor’s unbinding process, His66′ was a great supporter, that was absent in the weak inhibitor’s unbinding pathway. In contrast, in the weak inhibitor’s unbinding process, Trp98/Trp98′ by pi-pi stacking interactions were unfavorable for the stability of the inhibitor in the binding site. In our opinion, these results will assist in designing more potent and effective inhibitors for the HTLV-1 protease.
Catch bond models may explain how force amplifies TCR signaling and antigen discrimination
Authors: Choi Hyun-Kyu , Cong Peiwen , Ge Chenghao , Natarajan Aswin , Liu Baoyu , Zhang Yong , Li Kaitao , Rushdi Muaz Nik , Chen Wei , Lou Jizhong , Krogsgaard Michelle , Zhu Cheng
Published: January 2022

Central to T cell biology, the T cell receptor (TCR) integrates forces in its triggering process upon interaction with peptide-major histocompatibility complex (pMHC)1-3. Phenotypically, forces elicit TCR catch-slip bonds with strong pMHCs but slip-only bonds with weak pMHCs4-10. While such correlation is commonly observed, the quantitative bond pattern and degree of “catchiness” vary. We developed two models based on the structure, elastic properties, and force-induced conformational changes of the TCR–pMHC-I/II complexes to derive from their bond characteristics more intrinsic parameters that underlie structural mechanisms, predict T cell signaling, and discriminate antigens. Applying the models to 55 datasets of 12 αβTCRs and their mutants interacting with corresponding pMHCs without coreceptor engagement demonstrated the ability for structural and physical parameters to quantitatively integrate and classify a broad range of bond behaviors and biological activities. Comparing to the generic two-state model for catch-slip bond that also fits the data, our models can distinguish class I from class II MHC systems and their best-fit parameters correlate with the TCR/pMHC potency to trigger T cell activation, which the generic model cannot. The models were tested by mutagenesis using structural analysis, bond profile measurement, and functional assay of a MHC and a TCR mutated to alter conformation changes. The extensive comparisons between theory and experiment provided strong validation of the models and testable hypothesis regarding specific conformational changes that control bond profiles, thereby suggesting structural mechanisms for the inner workings of the TCR mechanosensing machinery and plausible explanation of why and how force may amplify TCR signaling and antigen discrimination.
Tracking Genomic Characteristics across Oceanic Provinces: Contrasting Early and Mature Plastic Biofilm Communities
Authors: Bos Ryan P. , Kaul Drishti , Zettler Erik R. , Hoffman Jeffrey M. , Dupont Christopher L. , Amaral-Zettler Linda A. , Mincer Tracy J.
Published: January 2022

While plastic has become omnipresent in the marine environment, knowledge of how plastic biofilm communities develop from functional metabolic and phylogenetic perspectives is nascent, although these data are central to understanding microbial ecology surrounding plastic substrates in the ocean. By incubating virgin microplastics during oceanic transects and comparing with naturally occurring plastic litter at the same locations, we constructed functional gene catalogs to contrast the metabolic differences between early and mature biofilm communities. Early colonization incubations were consistently dominated by Alteromonadaceae and harbored significantly higher proportions of genes associated with adhesion, biofilm formation, chemotaxis, defense, iron acquisition and utilization, and motility. Comparative genomic analyses with Alteromonas, Marinobacter, and Marisediminitalea metagenome assembled genomes (MAGs) spotlighted the importance of the mannose-sensitive hemagglutinin operon, adhesive genes genetically transposed from intestinal pathogens, for early colonization of hydrophobic plastic surfaces. Synteny alignments of the former operon also demonstrated apparent positive selection for mshA alleles across all MAGs. Early colonizers varied little in terms of large-scale genomic characteristics, despite the presence of latitudinal, salinity, and temperature gradients. Mature plastic biofilms, composed of predominantly Rhodobacteraceae followed by Flavobacteriaceae, that are critically important for carbon turnover in oceanic ecosystems, displayed significantly higher proportions of genes involved in oxidative phosphorylation, phosphonate metabolism, photosynthesis, secondary metabolism, and Type IV secretion. Our metagenomic analyses provide insight into early biofilm formation on virgin surfaces in the marine environment, as well as how early colonizers self-assemble, compared to mature, taxonomically, and metabolically diverse biofilms.

Significance Statement

Little is known about plastic biofilm assemblage dynamics and successional changes over time. Our results demonstrate that highly reproducible and predictable types of bacteria, with similar genomic characteristics, can initially colonize plastic in the marine environment across varying environmental gradients. The key gene sets involved in foundational bacterial colonization may have broad impacts for biofilm formation on plastic surfaces used in agriculture, biomedicine, environmental science, and food science. Genomic characteristics of early colonizers may metabolically underpin the origin of the ordered succession observed in marine microbial communities and be useful for predicting microbial community membership and biogeochemical processes.
Bridging the divide: understanding collaborative action in disability-inclusive disaster risk reduction through socio-cultural activity theory
Authors: Pertiwi Pradytia P.
Published: January 2022

Purpose

This paper presents a methodological reflection on the use of socio-cultural activity theory (SCAT) as a framework to understand collaborative action and problem-solving between people with disabilities and non-disabled stakeholders in three disaster risk reduction (DRR) initiatives led by Disabled People's Organisations (DPOs) in Indonesia.

Design/methodology/approach

This paper is based on case study research, using a multiple case design. It looks at the conception and implementation of three DPO-led DRR projects in Indonesia. It focuses hereby on the processes and outcomes of collaborations between DPOs and non-disabled stakeholders. It presents a reflection as to what extent the six elements of SCAT were present.

Findings

The investigation of SCAT's six elements captured the co-construction of DPO-led DRR projects and constant changes and transformation in implementation. The findings reveal the dynamics of the collaboration between DPOs and non-disabled stakeholders (e.g. funding donors, DRR experts, government and community groups) and its outcomes and learning points.

Practical implications

SCAT can provide a better understanding of collaborative learning processes and associated outcomes between DPOs and DRR actors. Such collaborations facilitate the timely and relevant inclusion of people with disabilities in DRR initiatives through DPOs' leadership in DRR. Furthermore, such initiatives can promote the realisation of the disability-inclusion principle of the Sendai Framework for DRR, which is underpinned by the all-of-society approach to DRR.

Originality/value

This paper presents a reflection on the use of SCAT in inclusive disaster studies, thereby enabling further investigation and understanding of how the collaboration between disabled and non-disabled stakeholders occurs, and its implication. This is a topic that has been rarely tackled in the disability and disaster studies literature and practice.
How does intelligent technology investment affect employment compensation and firm value in Chinese financial institutions?
Authors: Lai Zhoujing , Luo Hang (Robin)
Published: January 2022

Purpose

The authors intend to expand the literature on the relationship between intelligent technology and human resources in operating cost, and firm value of financial institutions in emerging markets by integrating the influence of intelligent technology and contribute to a growing body of literature on the determinants of firm value.

Design/methodology/approach

This paper empirically investigates the impact of intelligent technology investment on employment compensation and firm value using a sample of 86 listed financial institutions in China from 2010 to 2019.

Findings

This paper reports robust evidence that an increase in intelligent technology investment has a significantly negative effect on employment compensation in financial institutions. In addition, this inhibitory effect is persistent. The increase in intelligent investment has a significant two-year lag effect on firm value, which is positive and sustained. This indicates that intelligent technology investment has a short-term “useless” effect but brings long-term “gains” for Chinese financial institutions.

Originality/value

These findings may shed light on the decision-making processes of financial institutions, which helps practitioners better understand that firms need to reasonably deal with the subsequent cost of growth caused by intelligent technology input. Alternatively, they may wish to select the appropriate accounting method of depreciation or amortization to smooth its impact.
Feature selection for measurement models
Authors: Mueller Tobias , Segin Alexander , Weigand Christoph , Schmitt Robert H.
Published: January 2022

Purpose

In the determination of the measurement uncertainty, the GUM procedure requires the building of a measurement model that establishes a functional relationship between the measurand and all influencing quantities. Since the effort of modelling as well as quantifying the measurement uncertainties depend on the number of influencing quantities considered, the aim of this study is to determine relevant influencing quantities and to remove irrelevant ones from the dataset.

Design/methodology/approach

In this work, it was investigated whether the effort of modelling for the determination of measurement uncertainty can be reduced by the use of feature selection (FS) methods. For this purpose, 9 different FS methods were tested on 16 artificial test datasets, whose properties (number of data points, number of features, complexity, features with low influence and redundant features) were varied via a design of experiments.

Findings

Based on a success metric, the stability, universality and complexity of the method, two FS methods could be identified that reliably identify relevant and irrelevant influencing quantities for a measurement model.

Originality/value

For the first time, FS methods were applied to datasets with properties of classical measurement processes. The simulation-based results serve as a basis for further research in the field of FS for measurement models. The identified algorithms will be applied to real measurement processes in the future.
Effects of learning and uncertainty on crowdsourcing performance of solvers: insights from performance feedback theory
Authors: Ye Hua (Jonathan)
Published: January 2022

Purpose

In crowdsourcing contests, the capabilities and performance of individual workers (solvers) determine whether seeker firms can obtain satisfactory solutions from the platform. It is noted that solvers may learn such skills in crowdsourcing from doing (experiential learning) or observing (vicarious learning). However, it remains unclear if such learning can be materialized into improved performance considering the unique settings of crowdsourcing contests. The study aims to understand how experiential learning and vicarious learning enhance solver performance and under what conditions.

Design/methodology/approach

The model was tested using survey and archival data from 261 solvers on a large contest platform in China.

Findings

Results support the premise that experiential learning and vicarious learning separately and jointly enhance solver performance. Moreover, perceived task uncertainty strengthens the effect of vicarious learning but weakens the effect of experiential learning, whereas perceived competition uncertainty weakens the effect of vicarious learning.

Originality/value

The current study enriches the understanding of the impacts of experiential learning and vicarious learning and offers a more nuanced understanding of the conditions under which solvers can reap the performance benefits from learning in crowdsourcing contests. The study also provides practical insights into enhancing solver performance under perceived task uncertainty and perceived competition uncertainty.
Board of director's effectiveness, audit quality and ownership structure: impact on audit risk-Tunisian evidence
Authors: Fakhfakh Imen , Jarboui Anis
Published: January 2022

Purpose

The purpose of this paper is to investigate the potential influence of internal and external corporate governance mechanisms on audit risk in Tunisian companies.

Design/methodology/approach

Based on a sample of Tunisian non-financial firms listed on the Tunisian Stock Exchange (TSE) over the periods 2005 to 2010 (pre- 2011 revolution) and 2011 to 2017 (post −2011 revolution), consisting of 371 observations for the whole period, the authors apply the generalized least square (GLS) to test the research hypotheses and model.

Findings

The results are consistent with the agency theory suggesting that efficient corporate governance is able to control and reduce a company’s agency problem. Evidence reveals that the effectiveness of the director’s board/ownership structure and audit quality have the most influence on audit risk before than after the 2011 revolution, although governance mechanisms should play a more active role in encouraging companies to be more transparent in the post-revolution period. Moreover these findings are confirmed when identifying a composite measure of corporate governance.

Practical implications

Significant implications are provided for analysts, investors, regulators and academics. First, findings can help Tunisian regulators determine corporate governance disclosure requirements. Second, this research will make investors and stakeholders aware of the fact that minimizing auditor risk will be effective in reducing agency problems in emerging markets like Tunisia. Then, this work can help researchers better understand and realize the corporate governance role in the quality of audit process and financial statements and encourage them to deeply and broadly investigate this issue on other emerging markets.

Originality/value

This study stands for an extension of the existing research on corporate governance and audit risk. It fills a research gap in the local context. In fact, the considered data are those of the pre- and post-revolution Tunisian market, mainly in periods of instability. Although emerging markets make up the vast majority of economic activity around the world, they have received limited attention in academic research.