bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe COVID‐19 represents an undiagnosed primary immunodeficiency in a high proportion of infected individuals
Authors: Gray Paul E , Bartlett Adam W , Tangye Stuart G
Published: April 2022

Since the emergence of the COVID‐19 pandemic in early 2020, a key challenge has been to define risk factors, other than age and pre‐existing comorbidities, that predispose some people to severe disease, while many other SARS‐CoV‐2‐infected individuals experience mild, if any, consequences. One explanation for intra‐individual differences in susceptibility to severe COVID‐19 may be that a growing percentage of otherwise healthy people have a pre‐existing asymptomatic primary immunodeficiency (PID) that is unmasked by SARS‐CoV‐2 infection. Germline genetic defects have been identified in individuals with life‐threatening COVID‐19 that compromise local type I interferon (IFN)‐mediated innate immune responses to SARS‐CoV‐2. Remarkably, these variants – which impact responses initiated through TLR3 and TLR7, as well as the response to type I IFN cytokines – may account for between 3% and 5% of severe COVID‐19 in people under 70 years of age. Similarly, autoantibodies against type I IFN cytokines (IFN‐α, IFN‐ω) have been detected in patients' serum prior to infection with SARS‐CoV‐2 and were found to cause c. 20% of severe COVID‐19 in the above 70s and 20% of total COVID‐19 deaths. These autoantibodies, which are more common in the elderly, neutralise type I IFNs, thereby impeding innate antiviral immunity and phenocopying an inborn error of immunity. The discovery of PIDs underlying a significant percentage of severe COVID‐19 may go some way to explain disease susceptibility, may allow for the application of targeted therapies such as plasma exchange, IFN‐α or IFN‐β, and may facilitate better management of social distancing, vaccination and early post‐exposure prophylaxis.
NUTM1‐fusion positive malignant neoplasms of the genitourinary tract: A report of six cases highlighting involvement of unusual anatomic locations and histologic heterogeneity
Authors: Xu Bin , Chen Jie‐Fu , Sarungbam Judy , Tickoo Satish , Dickson Brendan C. , Reuter Victor E. , Antonescu Cristina R.
Published: April 2022

Tumors with NUTM1 fusions occur predominantly in the thoracic cavity and head and neck region. However, recent literature expanded the location of NUTM1‐translocated malignancy to soft tissue, brain, and visceral organs. In this study, we describe the first series of six NUTM1‐translocated carcinomas and sarcomas occurring in the genitourinary tract. The sites of origin were kidney (n = 2), bladder (n = 3), and penis (n = 1). All tumors occurred in adulthood (range: 30–78 years). The histologic features were heterogeneous, showing epithelial, spindle cell, or primitive small blue round cell morphology. Glandular architecture, keratinization, rhabdoid cells, or myxoid‐to‐edematous stromal component were also noted. In three cases, features were in keeping with a carcinoma (two from kidney and one from bladder), whereas the remaining three were classified as malignant undifferentiated neoplasm (MUN)/sarcoma. Fusion partners detected in four cases tested by either FISH and/or RNA sequencing were BRD4 in two kidney tumors, MXD1 in a bladder sarcoma, and MXD4 in a penile sarcoma. NUT immunostain showed diffuse spiculated positivity in five cases. Immunopositivity for various cytokeratins was noted in two tumors. The outcome of NUTM1‐rearranged genitourinary malignancy was dismal: four of five cases with follow‐up developed distant metastasis, and three suffered disease‐specific death. In conclusion, NUTM1‐rearranged carcinoma and sarcoma can affect the genitourinary tract, including kidney, bladder, and penis. Histologic features and keratin immunoexpression are highly variable. A NUTM1‐fusion positive malignancy may be included in the differential diagnosis of a MUN of the genitourinary tract given the dismal outcome and the existing BET‐targeted therapy for tumors with BRD3/4::NUTM1 fusion.
Prognostic impact of copy number alterations and tumor mutational burden in carcinoma of unknown primary
Authors: Bochtler Tilmann , Wohlfromm Timothy , Hielscher Thomas , Stichel Damian , Pouyiourou Maria , Kraft Bianca , Neumann Olaf , Endris Volker , von Deimling Andreas , Stenzinger Albrecht , Krämer Alwin
Published: April 2022

Introduction

Chromosomal aberrations are known to drive metastatic spread, but their profile is still elusive in carcinoma of unknown primary (CUP). Therefore, the aim of this study was to characterize the chromosomal aberration pattern in CUP depending on histological and clinical features and to assess its prognostic impact together with chromothripsis, tumor mutational burden (TMB), microsatellite instability (MSI), and mutational profiles as potential prognostic biomarkers.

Methods

Chromosomal aberrations and chromothripsis were detected by methylation‐based copy number variation (CNV) analysis, whereas TMB and MSI were calculated based on large next‐generation sequencing (NGS) panels. Putative primaries were assigned by consensus between two independent oncologists.

Results

CNV losses varied depending on putative primaries and were more abundant in patients harboring TP53 mutations and/or deletions 17p. CNV loss was prognostically adverse in localized CUP treated with surgery and/or radiotherapy, but not in disseminated poor‐risk CUP treated with palliative chemotherapy. CNV loss also worsened the prognosis in squamous cell CUP. Chromothripsis was detected in 18/59 (30.5%) patients without prognostic effect. TMB was highest in cases with MSI, squamous cell histology, and with lung, anal or cervical putative primaries.

Conclusion

Overall, CNV, chromothripsis, TMB, and MSI profiles in CUP are reminiscent of biological characteristics known from other cancer entities without a unifying CUP‐specific signature. Markedly, high‐level CNV loss is an adverse predictive biomarker in localized but not disseminated chemotherapy‐treated CUP. This implies that chromosomal losses drive CUP progression, but also increase susceptibility to chemotherapy, with both effects apparently leveling out in disseminated CUP.
Tight association between microbial eukaryote and giant virus communities in the Arctic Ocean
Authors: Xia Jun , Kameyama Sohiko , Prodinger Florian , Yoshida Takashi , Cho Kyoung‐Ho , Jung Jinyoung , Kang Sung‐Ho , Yang Eun‐Jin , Ogata Hiroyuki , Endo Hisashi
Published: April 2022

Viruses are important regulatory factors of the marine microbial community including microeukaryotes. However, little is known about their role in the northern Chukchi Sea in the Arctic basin, which has oligotrophic conditions in summer. To clarify the link between microbial eukaryotic communities and viruses as well as environmental conditions, we investigated the community structures of microeukaryotes (from 3 to144 μm and from 0.23 μm size bio‐particles collected from seawater) and Imitervirales (from 0.23 μm size bio‐particles collected from seawater), a dominant group of viruses infecting marine microeukaryotes. To the best of our knowledge, no study has investigated both Imitervirales and eukaryotic communities in the Arctic Ocean. Surface water samples were collected at 21 ocean stations located in the northeastern Chukchi Sea and an adjacent area outside the Beaufort Gyre (Adjacent Sea), and at two melt ponds on sea ice in the summer of 2018. At the ocean stations, nutrient concentrations were low in most of the locations, except the shelf in the adjacent sea. The community variations were significantly correlated between eukaryotes and Imitervirales, even within the northeastern Chukchi Sea characterized by relatively homogeneous environmental conditions. The association of the eukaryotic community with the viral community was stronger than that with geographical and physicochemical environmental factors. These results suggest that Imitervirales actively infect their hosts even in the cold and oligotrophic seawater in the Arctic Ocean.
SARS-CoV-2 and neurodegenerative diseases: what we know and what we don’t
Authors: Lingor Paul , Demleitner Antonia F. , Wolff Andreas W. , Feneberg Emily
Published: April 2022

Infection of the CNS with the SARS-CoV-2 can occur via different routes and results in para- or post-infectious manifestations with a variety of neurological symptoms. In patients with neurodegenerative diseases, SARS-CoV-2 is often associated with a higher fatality rate, which is a relevant problem in increasingly older populations. Apart from the direct consequences of an infection in patients with neurodegenerative diseases, indirect consequences of the pandemic such as limited access to care facilities and treatment have negative effects on the course of these chronic disorders. The occurrence of long-lasting neurological symptoms after infection with SARS-CoV-2 indicates a prolonged impact on the CNS. However, while it is known that SARS-CoV-2 affects neuronal populations that are relevant in the pathogenesis of neurodegenerative diseases, it is yet unclear whether an infection with SARS-CoV-2 is sufficient to trigger neurodegeneration. Reflecting on the impact of SARS-CoV-2 on neurodegeneration, we provide a concise overview on the current knowledge of SARS-CoV-2-induced pathology in the CNS and discuss yet open questions in the field.
Enhancing the performance of smart electrical grids using data mining and fuzzy inference engine
Authors: El-Balka Rana Mohamed , Saleh Ahmed I. , Abdullah Ahmed A. , Sakr Noha
Published: April 2022

This paper is about enhancing the smart grid by proposing a new hybrid feature-selection method called feature selection-based ranking (FSBR). In general, feature selection is to exclude non-promising features out from the collected data at Fog. This could be achieved using filter methods, wrapper methods, or a hybrid. Our proposed method consists of two phases: filter and wrapper phases. In the filter phase, the whole data go through different ranking techniques (i.e., relative weight ranking, effectiveness ranking, and information gain ranking) The results of these ranks are sent to a fuzzy inference engine to generate the final ranks. In the wrapper phase, data is being selected based on the final ranks and passed on three different classifiers (i.e., Naive Bayes, Support Vector Machine, and neural network) to select the best set of the features based on the performance of the classifiers. This process can enhance the smart grid by reducing the amount of data being sent to the cloud, decreasing computation time, and decreasing data complexity. Thus, the FSBR methodology enables the user load forecasting (ULF) to take a fast decision, the fast reaction in short-term load forecasting, and to provide a high prediction accuracy. The authors explain the suggested approach via numerical examples. Two datasets are used in the applied experiments. The first dataset reported that the proposed method was compared with six other methods, and the proposed method was represented the best accuracy of 91%. The second data set, the generalization data set, reported 90% accuracy of the proposed method compared to fourteen different methods.
Ideas, hopes, and fears: what young adults think about genome editing, nature, and society
Authors: Ebeling Smillo , Gebhard Ulrich
Published: April 2022

Gene technologies are developing at a high speed. Yet, the understandings and ethical conceptions about these developments are not sufficiently scrutinized and reflected. Our qualitative analysis examines everyday myths of younger generations about genome editing; these contribute to a complex fabric of rationally and intuitively justified opinions on genome editing. We argue that current thought patterns and social ways of thinking co-constitute the everyday myths. On the basis of group discussions with teenagers and students about genome editing, we reconstruct their topical views of humanity, the world, science and technology, value orientations, fears, hopes, and desires that are connected to genome editing. Our focus is on everyday myths about health and nature (particularly the nature–culture dichotomy) as well as their implications for social developments in the times of genome editing. Among these developments feared by the young generations are first and foremost conceptions regarding population density, environmental destruction, family relationships, normalization processes, and nature as a fundamental normative authority. The juveniles and students also reflect abstract ideals, e.g., perfection and health, within their contexts, and demystify these ideals.
Decomposing the effects of digitalization on workers’ job satisfaction
Authors: Bolli Thomas , Pusterla Filippo
Published: April 2022

This paper provides novel results on the relative importance of multiple channels through which digitalization affects job satisfaction. Using part-time students and graduates of professional education and training colleges in Switzerland as a case study, we investigate the relative strength of ten different channels. We find that the association between digitalization and job satisfaction is positive on average. This relationship is mainly due to the increase in productivity and more interesting work. Heterogeneity analyses on subsets of workers suggest that the effect through increasing productivity is more beneficial for women, for older workers, for workers without an executive position, and for workers who did not study in technology-related fields. The effect through the interestingness of work is larger for males and for older workers. Our results further suggest that among the channels that decrease job satisfaction, increase of time pressure and worsening of work-life balance are much more important than the threat of losing one’s job. Both channels are more relevant for men, for older workers, and for workers whose field of study is technology-related.
Adaptive personalized routing for vulnerable road users
Authors: Darko Justice , Folsom Larkin , Pugh Nigel , Park Hyoshin , Shirzad Khadijeh , Owens Justin , Miller Andrew
Published: April 2022

This research presents an adaptive and personalized routing model that enables individuals with mobility impairments to save their route preferences to a mobility assistant platform. The proactive approach based on anticipated user need accommodates vulnerable road users' personalized optimum dynamic routing rather than a reactive approach passively awaiting input. Most currently available trip planners target the general public's use of simpler route options prioritized based on static road characteristics. These static normative approaches are only satisfactory when conditions of intermediate intersections in the network are consistent, a constant rate of change occurs per each change of the segment condition, and the same fixed routes are valid every day regardless of the user preference. In this study, the vulnerable road user mobility problem is modeled by accommodating personalized preferences changing by time, sidewalk segment traversability, and the interaction between sidewalk factors and weather conditions for each segment contributing to a path choice. The developed reinforcement learning solution presents a lower average cost of personalized, accessible, and optimal path choices in various trip scenarios and superior to traditional shortest path algorithms (e.g., Dijkstra) with static and dynamic extensions.
Blockade of Microglial Activation in Hypothalamic Paraventricular Nucleus Improves High Salt-Induced Hypertension
Authors: Yu Xiao-Jing , Liu Xiao-Jing , Guo Jing , Su Yu-Kun , Zhang Nianping , Qi Jie , Li Ying , Fu Li-Yan , Liu Kai-Li , Li Yanjun , Kang Yu-Ming
Published: April 2022

BACKGROUND

It has been shown that activated microglia in brain releasing proinflammatory cytokines (PICs) contribute to the progression of cardiovascular diseases. In this study, we tested the hypothesis that microglial activation in hypothalamic paraventricular nucleus (PVN), induced by high-salt diet, increases the oxidative stress via releasing PICs and promotes sympathoexcitation and development of hypertension.

METHODS

High-salt diet was given to male Dahl salt-sensitive rats to induce hypertension. Those rats were bilaterally implanted with cannula for PVN infusion of minocycline, a selective microglial activation blocker, or artificial cerebrospinal fluid for 4 weeks.

RESULTS

High-salt diet elevated mean arterial pressure of Dahl salt-sensitive rats. Meanwhile, elevations of renal sympathetic nerve activity and central prostaglandin E2, as well as increase of plasma norepinephrine, were observed in those hypertensive rats. Tumor necrosis factor-α, interleukin-1β (IL-1β), and IL-6 increased in the PVN of those rats, associated with a significant activation of microglia and prominent disruption of redox balance, which was demonstrated by higher superoxide and NAD(P)H oxidase 2 (NOX-2) and NAD(P)H oxidase 4 (NOX-4), and lower Cu/Zn superoxide dismutase in PVN. PVN infusion of minocycline attenuated all hypertension-related alterations described above.

CONCLUSION

This study indicates that high salt leads to microglial activation within PVN of hypertensive rats, and those activated PVN microglia release PICs and trigger the production of reactive oxygen species, which contributes to sympathoexcitation and development of hypertension. Blockade of PVN microglial activation inhibits inflammation and oxidative stress, therefore attenuating the development of hypertension induced by high-salt diet.
Tamponade dressing versus no dressing after haemorrhoidectomy: multicentre, randomized clinical trial
Authors: Langenbach Mike Ralf , Florescu Razvan-Valentin , Köhler Andreas , Barkus Jörg , Ritz Jörg-Peter , Quemalli Eduart , Siegel Robert , Zirngibl Hubert , Lefering Rolf , Bönicke Lars
Published: April 2022

Background

Symptomatic haemorrhoids are a common anorectal disorder. The aim of the study was to investigate whether the omission of tamponade dressings after haemorrhoidectomy reduces postoperative pain without increasing the risk of severe bleeding.

Method

This was an open-label, randomized clinical trial conducted at 14 German hospitals. All patients with third- or fourth-degree haemorrhoids undergoing haemorrhoidectomy were considered eligible for selection in the intervention (no dressing) or control group (tamponade applied). Two co-primary outcomes were analysed by testing hierarchically ordered hypotheses. First, maximum pain intensity within 48 h after surgery was compared between the groups (superiority). This was followed by an analysis of severe bleeding complications, defined as any bleeding requiring surgical re-intervention within 7 days (non-inferiority). Secondary outcomes included health-related quality of life, patient satisfaction, haemoglobin levels, and adverse events.

Results

Out of 950 patients screened, 754 were randomized and 725 received intervention (366 patients in the intervention and 359 patients in the control group). In the group with tamponade dressings, median pain intensity on the 0 to 10 scale was 6 (interquartile range (i.q.r.) 4–7). Patients without tamponade dressings reported significantly less pain (median 5 (i.q.r. 3–7), P < 0.001). In each group, five patients (1.4 per cent) experienced severe bleeding. The absolute difference for the severe bleeding rate was −0.03 per cent with the 90 per cent confidence interval ranging from −1.47 per cent to +1.41 per cent, in line with the non-inferiority aim. No significant between-group difference was found for secondary outcomes.

Conclusions

The practice of inserting tamponade dressings after haemorrhoidectomy correlates with increased postoperative pain and does not provide benefits in terms of reduced postoperative bleeding.

Registration number

DRKS00011590
Effects of the COVID-19 pandemic on early career neuroscientists
Authors: Spires-Jones Tara L.
Published: April 2022

Our editor discusses the emerging effects of the COVID-19 pandemic on early career neuroscientists.
Structured Understanding of Assessment and Plans in Clinical Documentation
Authors: Stupp Doron , Barequet Ronnie , Lee I-Ching , Oren Eyal , Feder Amir , Benjamini Ayelet , Hassidim Avinatan , Matias Yossi , Ofek Eran , Rajkomar Alvin
Published: April 2022

Physicians record their detailed thought-processes about diagnoses and treatments as unstructured text in a section of a clinical note called the assessment and plan. This information is more clinically rich than structured billing codes assigned for an encounter but harder to reliably extract given the complexity of clinical language and documentation habits. We describe and release a dataset containing annotations of 579 admission and progress notes from the publicly available and de-identified MIMIC-III ICU dataset with over 30,000 labels identifying active problems, their assessment, and the category of associated action items (e.g. medication, lab test). We also propose deep-learning based models that approach human performance, with a F1 score of 0.88. We found that by employing weak supervision and domain specific data-augmentation, we could improve generalization across departments and reduce the number of human labeled notes without sacrificing performance.
Whole Genome DNA and RNA Sequencing of Whole Blood Elucidates the Genetic Architecture of Gene Expression Underlying a Wide Range of Diseases
Authors: Liu Chunyu , Joehanes Roby , Ma Jiantao , Wang Yuxuan , Sun Xianbang , Keshawarz Amena , Sooda Meera , Huan Tianxiao , Hwang Shih-Jen , Bui Helena , Tejada Brandon , Munson Peter J. , Cumhur Demirkale , Heard-Costa Nancy L. , Pitsillides Achilleas N , Peloso Gina M. , Feolo Michael , Sharopova Nataliya , Vasan Ramachandran S. , Levy Daniel
Published: April 2022

To create a scientific resource of expression quantitative trail loci (eQTL), we conducted a genome-wide association study (GWAS) using genotypes obtained from whole genome sequencing (WGS) of DNA and gene expression levels from RNA sequencing (RNA-seq) of whole blood in 2622 participants in Framingham Heart Study. We identified 6,778,286 cis-eQTL variant-gene transcript (eGene) pairs at p<5×10−8 (2,855,111 unique cis-eQTL variants and 15,982 unique eGenes) and 1,469,754 trans-eQTL variant-eGene pairs at p<1e-12 (526,056 unique trans-eQTL variants and 7,233 unique eGenes). In addition, 442,379 cis-eQTL variants were associated with expression of 1518 long non-protein coding RNAs (lncRNAs). Gene Ontology (GO) analyses revealed that the top GO terms for cis-eGenes are enriched for immune functions (FDR <0.05). The cis-eQTL variants are enriched for SNPs reported to be associated with 815 traits in prior GWAS, including cardiovascular disease risk factors. As proof of concept, we used this eQTL resource in conjunction with genetic variants from public GWAS databases in causal inference testing (e.g., COVID-19 severity). After Bonferroni correction, Mendelian randomization analyses identified putative causal associations of 60 eGenes with systolic blood pressure, 13 genes with coronary artery disease, and seven genes with COVID-19 severity. This study created a comprehensive eQTL resource via BioData Catalyst that will be made available to the scientific community. This will advance understanding of the genetic architecture of gene expression underlying a wide range of diseases.
The use of obinutuzumab and ofatumumab in the treatment of immune thrombotic thrombocytopenic purpura
Authors: Doyle Andrew J. , Stubbs Matthew J. , Lester Will , Thomas Will , Westwood John‐Paul , Thomas Mari , Percy Charles , Prasannan Nithya , Scully Marie
Published: April 2022

Rituximab, an anti‐CD20 monoclonal antibody, can be used to treat immune thrombotic thrombocytopenic purpura (iTTP) during acute presentation or disease relapse. Undesirable side‐effects include severe hypersensitivity reactions, particularly anaphylaxis and rituximab‐induced serum sickness, with a minority not maintaining a response to treatment. Alternative humanised anti‐CD20 treatments, obinutuzumab and ofatumumab, have been used. A review of the UK TTP Registry showed 15 patients received these drugs over 26 treatment episodes (eight obinutuzumab and 18 ofatumumab). Indications for alternative anti‐CD20 treatment were severe infusion‐related reactions, acute rituximab‐induced serum sickness and a short duration of disease remission. All patients achieved disease remission (ADAMTS13 [A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13] activity ≥30 iu/dl) after a median 15 days and 92% of episodes achieved complete remission (≥60 iu/dl). Seven patients required further treatment for disease relapse with a median relapse‐free survival of 17.4 months. All patients continued to respond to re‐treatment with the preceding drug when relapse occurred. There were four adverse events in 26 treatment episodes (15%) – two infections and two infusion reactions. These results suggest that obinutuzumab and ofatumumab may be considered as an alternative option to rituximab in the treatment of iTTP with a comparable safety profile, absence of significant hypersensitivity reactions and sustained normalisation of ADAMTS13.
Lack of congruence between fundamental and realised aridity niche in a lineage of water beetles
Authors: Pallarés Susana , Millán Andrés , Lobo Jorge M. , Pérez Abraham , Sánchez‐Fernández David
Published: April 2022

Coping with aridity is a physiological challenge for all organisms, including freshwater ones. Aridity shapes distributions of aquatic species at fine and large geographical scales. Specifically, for aquatic beetles, the desiccation resistance of the adults is a potential constraint for the colonisation of arid regions.

We assessed the congruence between the fundamental and realised aridity niche in eight species of a Palearctic lineage of water beetles (subgenus Lumetus, genus Enochrus, family Hydrophilidae). We also estimated the relative explanatory capacity of aridity‐related versus other environmental variables in species distributions.

Most of the species, even those most sensitive to desiccation stress in laboratory experiments, occur in areas with high aridity within the Palearctic region. Our results suggest a lack of association between the physiological (desiccation resistance) and environmental distance matrix (realised aridity niche), or between either of these and phylogenetic distances. Aridity‐related variables had generally a similar explanatory capacity in explaining the distribution of species than non‐related ones.

Our results indicate that desiccation resistance has not been an important physiological constraint for the colonisation of arid environments by this clade and suggest that other non‐physiological factors are more important in shaping their distributions along aridity gradients. The studied beetle lineage might conserve a high basal desiccation resistance from relatively recent terrestrial ancestors, which could have provided a physiological advantage for the colonisation of arid areas. Further research could shed light on whether these unexpected results are common to other groups of aquatic insects living in arid areas or are particular to this group of beetles.
Stimulatory role of nectin‐4 and p95‐ErbB2 in multilayered T47D cell proliferation
Authors: Kedashiro Shin , Kameyama Takeshi , Mizutani Kiyohito , Takai Yoshimi
Published: April 2022

Multilayered proliferation in an adherent culture as well as proliferation in a suspension culture is a characteristic feature of cancer cells. We previously showed using T47D human mammary cancer cells that nectin‐4, upregulated in many cancer cells, cis‐interacts with ErbB2 and its trastuzumab‐resistant splice variants, p95‐ErbB2 and ErbB2ΔEx16, and enhances DNA synthesis mainly through the PI3K‐AKT pathway in an adherent culture. We showed here that only the combination of nectin‐4 and p95‐ErbB2, but not that of nectin‐4 and ErbB2 or that of nectin‐4 and ErbB2ΔEx16, cooperatively enhanced multilayered T47D cell proliferation through the Hippo pathway–mediated SOX2 gene expression in an adherent culture. T47D cells expressed the components of the apical junctional complex (AJC) consisting of adherens junctions (AJs) and tight junctions and cell polarity molecules, but not the AJ component afadin. The AJC and apicobasal polarity were disorganized in T47D cells in a monolayer and T47D cells stably expressing both nectin‐4 and p95‐ErbB2 in multilayers. These results indicate that nectin‐4 and p95‐ErbB2 play a stimulatory role in multilayered proliferation in an adherent culture.
Predictors for the detection of arrhythmia requiring pacemaker/ICD implantation—Results from a loop recorder study
Authors: Kreimer Fabienne , Aweimer Assem , Backhaus Julian Felix , Pflaumbaum Andreas , Mügge Andreas , Gotzmann Michael
Published: April 2022

Background

There are few large studies on which factors are associated with the occurrence of arrhythmias. Implantable loop recorders (ILR) are useful in detecting arrhythmia due to prolonged and continuous ECG monitoring. Therefore, the aim of this study is to identify and evaluate clinical characteristics and ECG parameters for predicting arrhythmias requiring pacemaker/ICD implantation by analyzing a study cohort with ILR.

Methods

This bicentric study comprised a study cohort of 451 patients (mean age 64 ± 16 years, 209 women) receiving ILR implantation between 2011 and 2021. Patients were followed up on a 3 monthly outpatient interval. All arrhythmias with a pacemaker or ICD indication were considered clinically relevant. The primary study endpoint was the detection of clinically relevant arrhythmia.

Results

During a follow up of 678 ± 392 days, a clinically relevant arrhythmia was detected in 81 of 451 patients (18%). Multivariate analysis revealed five independent risk factors: coronary artery disease (HR 1.954, CI 1.077–3.546, p = .028), atrial fibrillation (HR 2.253, CI 1.201–4.228, p = .011), previous syncope (HR 6.404, CI 3.202–12.808, p < .001), right bundle branch block (HR 4.370, CI 2.215–8.621, p < .001) and left bundle branch block (HR 2.685, CI 1.116–6.461, p = .028). Our risk model, based on these independent predictors, divided the study cohort into patients with low (2%), intermediate (18%), medium (34%), and high (45%) risk for clinically relevant arrhythmia.

Conclusion

By the use of ILR, a clinically relevant arrhythmia has been detected in almost one fifth of the study cohort. In addition, clinical and electrocardiographic parameters were shown to be suitable predictors of clinically relevant arrhythmia.
Motivated reasoning and the ethics of belief
Authors: Ellis Jon
Published: April 2022

In recent years,motivated reasoninghas received significant attention across numerous areas of philosophy, including political philosophy, social philosophy, epistemology, moral psychology, philosophy of science, even metaphysics. At the heart of much of this interest is the idea that motivated reasoning (e.g., rationalization, wishful thinking, and self‐deception) isproblematic, that it runs afoul of epistemic normativity, or is otherwise irrational. Is motivated reasoning epistemically problematic? Is it always? When it is, what is the nature of the violation? Philosophical projects on motivated reasoning require informed positions on these questions, demanding explicit engagement with fundamental issues about epistemic normativity and the ethics of belief. But attention to this has been limited, thwarting progress on a variety of critical questions. In this paper, I distinguish some of the key issues at play and discuss their interactions. At the end, I offer three methodological recommendations for future research on motivated reasoning.
Optical solitons in birefringent fibers with Sasa–Satsuma equation having multiplicative noise with Itô calculus
Authors: Zayed Elsayed M. E. , Alngar Mohamed E. M. , Shohib Reham M. A. , Biswas Anjan , Yıldırım Yakup , Triki Houria , Moshokoa Seithuti P. , Alshehri Hashim M.
Published: April 2022

This paper obtains soliton solutions to Sasa–Satsuma equation, which is studied in birefringent fibers with multiplicative noise. The extended auxiliary equation approach reveals solutions in terms of Jacobi’s elliptic functions from which bright, dark and singular solitons emerge when the limiting operation is applied to the modulus of ellipticity, with the limit approaching zero or unity.
A Discrete Approach to Feedback Linearization, Yaw Control of An Unmanned Helicopter
Authors: Mohammadzahri Morteza , Khaleghifar Arman , Ghodsi Mojtaba , Soltani Payam , AlSulti Sami
Published: April 2022

Nonlinear control laws often need to be implemented with digital hardware. Use of digital control systems leads to communication/processing delays which are widely neglected in control of mechanical systems. This paper proposes a discrete approach to feedback linearization that considers these commonly overlooked delays in design. The proposed approach is shown to both improve the performance and remove the need for continuous derivative terms. In feedback linearization control systems, designed in the continuous domain, derivative terms are required to speed up the control response of mechanical systems, but disadvantageously cause high sensitivity to noise. The proposed approach was used to design a feedback linearization control system for a common turning maneuver of an unmanned helicopter in yaw. At this maneuver, the helicopter centroid motion and pitch rotational speed are almost zero. Governing differential equations of the helicopter at this maneuver are nonlinear and coupled. A feedback linearization law was proposed to curb nonlinearity and, a discrete control system, considering the inevitable delay due to the use of digital control systems, was adopted to complete the control law. This innovative approach resulted in less sensitivity to noises and performance boost. Practical limits in terms of control input, rotor speed, sampling frequency and noises of the gyroscope, the tachometer and the acceleration sensor were taken into account in this research. The results show that the proposed control system leads to fast and smooth yaw turns even at a high pitch angle (close to vertical) or in the case of being hit by external objects.
Optimal exercise frontier of Bermudan options by simulation methods
Authors: Xie Dejun , Edwards David A. , Wu Xiaoxia
Published: April 2022

In this paper, a novel algorithm for determining the free exercise boundary for high-dimensional Bermudan option problems is presented. First, a rough estimate of the boundary is constructed on a fine (daily) time grid. This rough estimate is used to generate a more accurate estimate on a coarse time grid (exercise opportunities). Antithetic branching is used to reduce the computational workload. The method is validated by comparing it with other methods of solving the standard Black–Scholes problem. Finally, the method is applied to two cases of Bermudan options with a second stochastic variable: a stochastic interest rate and a stochastic volatility.
Wireless Communication for Robotic Process Automation Using Machine Learning Technique
Authors: Murugamani C. , Sahoo Santosh Kumar , Kshirsagar Pravin R. , Prathap Boppuru Rudra , Islam Saiful , Noorulhasan Naveed Quadri , Hussain Mohammad Rashid , Hung Bui Thanh , Teressa Dawit Mamiru
Published: April 2022

Machine intelligence is what has been generated by programming computers with certain aspects of human intellect, like training, solving problems, and priority setting. A machine can solve a number of complicated issues using these capabilities. In major industries, such as customer support and manufacturing, machine intelligence is now being employed. The growth and quick development of digital technology and artificial intelligence (AI) technologies are becoming more and more difficult. At now, sophisticated manufacturing, the world of invention, and broad acceptance are undergoing a fast transition. Robotics is much more vital as it may now be related to the human brain by the connection between machine and brain, as AI develops. The world’s economy faces substantial difficulties by increasing productivity in the manufacturing industry. This study examines the present progress of robotic communication styles of artificial intelligence (AI). In many specific applications, communication between members of a robotic group or even people becomes vital. The paper solves the problem of implementation of an independent industry mobile robot in all fields in the major business, live interactive, planning, mobile robot technologies, and intending. In order to identify the best solution to this issue, a mixed integer robotic model has been developed.
Performance Evaluation of SeisTutor Using Cognitive Intelligence‐Based “Kirkpatrick Model”
Authors: Singh Ninni , Gunjan Vinit Kumar , Kadiyala Ramana , Xin Qin , Gadekallu Thippa Reddy
Published: April 2022

The classroom learning environment facilitates human tutors to interact with every learner and get the opportunity to understand the learner’s psychology and then provide learning material (access learner prior knowledge and well align the learning material as per learner requirement) to them accordingly. Implementing this cognitive intelligence in intelligent tutoring system is quite tricky. This research has focused on mimicking human tutor cognitive intelligence in the computer-aided system of offering an exclusive curriculum to the learners. The prime focus of this research article is to evaluate the proposed SeisTutor using Kirkpatrick’s four-phase evaluation model. Experimental results depicting the enhanced learning gain through intelligence incorporated SeisTutor as against the intelligence absence are demonstrated.
The Convertible Learning System: A Certainty for Uncertain Times
Authors: Abuhmaid Atef , Kaur Irameet , Joordens Steve
Published: April 2022

In light of our forced migration to the online world, this article argues in favor of a widespread evolution of our approach to education, drifting from rigid to flexible models. Such an optimal system would be able to change from one form and function to another, even in mid-course, without compromising pedagogy. This system has to be based on evidence-based innovative pedagogies and scholarships of teaching and learning. The article proposes a “Convertible Learning System” (CLS)—a synergistic optimization of relative strengths of traditional and online learning approaches, while simultaneously allowing the flexibility that we realize is now critical. Although the examples lie in the realms of tertiary education, the concepts and implications can be beneficial at educational levels.
Plasma haemolysis index and interleukine-6 for the early prediction of cardiac surgery-associated acute kidney injury. A proof-of-concept study
Authors: Lakhal Karim , Rozec Bertrand , Souab Fouzia , Senage Thomas , Leroy Maxime , Legrand Arnaud , Boissier Elodie , Bigot-Corbel Edith
Published: April 2022

Introduction

Haemolysis and inflammation contribute to cardiac surgery-associated acute kidney injury (CS-AKI). We aimed to assess the performance of plasma haemolysis index (HI) and interleukine-6 (IL-6) for the prediction of all-stage CS-AKI. We also assessed their ability to predict moderate-to-severe CS-AKI and to discriminate persistent from transient CS-AKI.

Methods

Adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) were prospectively included. Haemolysis index and IL-6 were measured immediately after the end of CPB and 6 hours later. Correction for haemodilution relied upon changes in albuminaemia. Persistent CS-AKI was defined as a steady/increasing CS-AKI stage between the 48th and the 60th postoperative hour as compared with the worst stage observed within the 48 first hours.

Results

Among 82 patients, CS-AKI occurred in 37 (45%) patients. Postoperative HI and IL-6 were positively correlated to the duration of CPB (r ≤ 0.51, p ≤ 0.0003). Whether we considered isolated measurements of HI or IL-6, their indexation to haemodilution or not, their kinetics and/or their combination, the prediction of all stage CS-AKI was inaccurate (area under the receiver operating characteristic curve [AUCROC]≤ 0.68) whereas moderate-to-severe CS-AKI (6 patients only) was predicted with an honourable performance (AUCROC = 0.77 [95%CI 0.67;0.86] and 0.87 [95%CI 0.77;0.93] for HI and IL-6, respectively). The persistent/transient nature of CS-AKI was inaccurately predicted (AUCROC ≤ 0.68).

Conclusions

In a population in which most CS-AKI cases were mild, although they frequently (41%) persisted >48 hours, CS-AKI was inaccurately predicted by HI and/or IL-6. A better performance for moderate-to-severe CS-AKI prediction is likely. These preliminary findings are yet to be validated.
Research on infilling strategy in surrogate-aided optimization for axial compressor blades
Authors: Liu Wei , Xu Yibing , He Ming , Yan Chong , Wang Qiujun , Piao Ying
Published: April 2022

The hybrid Voronoi-Latin Hypercube Sampling (Voronoi-LHS) method is proposed for the surrogate-aided optimization of the axial compressor blades. The hybrid method is first applied to the fundamental test cases. The analytical results show that, compared with the Voronoi and LHS strategies, the hybrid method generally improves the robustness and convergency. Then the multi-objective genetic algorithm (MOGA) in conjunction with the artificial neural network (ANN) is applied to optimize the aerodynamic performance of an axial compressor rotor. Before the optimization process, the hybrid Voronoi-LHS sample infilling method is employed to refine the ANN surrogate model. Considering the typical intake distortion, the sweep and lean distributions of this rotor are optimized to pursue the maximum total pressure ratio and adiabatic efficiency. The results show that the optimization significantly improves the pressure ratio, efficiency and surge margin of the compressor with low computing cost.
Introducing Fairy Comments: Gen Z’s Instrument of Online Kudos Trolling
Authors: Khanna Karman , Kataria Priya
Published: April 2022

Social media platforms have come a long way from being spaces for just informal interactions between friends and family. Today, these platforms provide numerous ways for people to express their ideas, views and opinions. In this article, we look at one such medium of expression that gained widespread popularity on Instagram during the 2020 pandemic. Popularly known as ‘fairy comments’, these are comments with a very typical syntactic structure used on social media platforms. The syntactic structure involves several emoticons in the middle of a sentence rather than the end. The aim is to define what a fairy comment is and understand the characteristics responsible for its popularity among the youth. We conducted in-depth interviews with 17 Gen Z participants who are active users of Instagram and fairy comment makers tractioning high engagement on their comments. Besides, a rhetorical criticism of high engagement comments on posts of an Indian political leader helped develop an anatomy of a fairy comment. Based on the findings, we propose that Gen Z’s inclination for using fairy comments in the online public sphere is contingent on two characteristics intrinsic to the nature of a fairy comment. First, the potential for creative expression that fairy comments provide, and second, the potential of fairy comments to tread on borders of offense but not harm as they steer clear of abuse or suggested violence in the online space. A collateral outcome of making fairy comments is a coalition between the youth on matters of public interest. These characteristics indicate that fairy comments constitute a medium of trolling under the ‘kudos trolling’ category used by the youth as an instrument of expression in the online space.
Out-of-home participation among people living with dementia: A study in four countries
Authors: Thalén Liv , Malinowsky Camilla , Margot-Cattin Isabel , Gaber Sophie N , Seetharaman Kishore , Chaudhury Habib , Cutchin Malcolm , Wallcook Sarah , Anders Kottorp , Brorsson Anna , Nygård Louise
Published: April 2022

Social participation in out-of-home activities is important for people living with dementia, yet little is known about such participation. The aim of this study was to explore and compare out-of-home participation among people living with dementia in four countries by assessing different types of places of participation visited or no longer visited. A cross-sectional design was used to gather self-reported experiences concerning out-of-home participation among people with mild stage dementia living in Canada ( n = 29), Sweden ( n = 35), Switzerland ( n = 35) and the UK ( n = 64). Interviews were conducted using the Participation in ACTivities and places OUTside the Home for older adults (ACT-OUT) instrument. Participants still visited 16 ( Median) places out of a possible total of 24, and they had abandoned 5 ( Median) places. Neighbourhood was the place most participants still visited, whereas 50% of them had stopped going to a Sports facility, with no significant differences between country samples regarding how many participants had abandoned that place (Fisher’s exact test, p > 0.01). There were significant differences between country samples in the frequency of present participation and abandonment of the Hospital, Dentist’s office, Cemetery, Garden, and Forest (Fisher’s exact test, all p < 0.01). Although the participants still visited a variety of places, they had stopped going to places previously visited, which indicates reductions in participation, posing an inherent risk to well-being. The similarities and differences across samples from the four countries suggest that healthcare services and access to public transport may contribute to the complex interactional process of out-of-home participation for people living with dementia. The findings highlight the need for initiatives targeting specific types of places to support continued participation in society, especially places at a higher risk of abandonment such as places for recreation and physical activity.
Predicting lymph node metastasis and prognosis of individual cancer patients based on miRNA-mediated RNA interactions
Authors: Ren Shulei , Lee Wook , Han Kyungsook
Published: April 2022

Background

Lymph node metastasis is usually detected based on the images obtained from clinical examinations. Detecting lymph node metastasis from clinical examinations is a direct way of diagnosing metastasis, but the diagnosis is done after lymph node metastasis occurs.

Results

We developed a new method for predicting lymph node metastasis based on differential correlations of miRNA-mediated RNA interactions in cancer. The types of RNAs considered in this study include mRNAs, lncRNAs, miRNAs, and pseudogenes. We constructed cancer patient-specific networks of miRNA mediated RNA interactions and identified key miRNA–RNA pairs from the network. A prediction model using differential correlations of the miRNA–RNA pairs of a patient as features showed a much higher performance than other methods which use gene expression data. The key miRNA–RNA pairs were also powerful in predicting prognosis of an individual patient in several types of cancer.

Conclusions

Differential correlations of miRNA–RNA pairs identified from patient-specific networks of miRNA mediated RNA interactions are powerful in predicting lymph node metastasis in cancer patients. The key miRNA–RNA pairs were also powerful in predicting prognosis of an individual patient of solid cancer.