bluuebunny/crossref_metadata_2025 huggingface dataset:
Negative impact of COVID-19 associated health system shutdown on patients diagnosed with colorectal cancer: a retrospective study from a large tertiary center in Ontario, Canada
Authors: Forse Catherine L. , Petkiewicz Stephanie , Teo Iris , Purgina Bibianna , Klaric Kristina-Ana , Ramsay Tim , Wasserman Jason K.
Published: August 2021

Background

In March 2020, a directive to halt all elective and non-urgent procedures was issued in Ontario, Canada because of COVID-19. The directive caused a temporary slowdown of screening programs including surveillance colonoscopies for colorectal cancer (CRC). Our goal was to determine if there was a difference in patient and tumour characteristics between CRC patients treated surgically prior to the COVID-19 directive compared to CRC patients treated after the slowdown.

Methods

CRC resections collected within the Champlain catchment area of eastern Ontario in the six months prior to COVID-19 (August 1, 2019-January 31, 2020) were compared to CRC resections collected in the six months post-COVID-19 slowdown (August 1, 2020-January 31, 2021). Clinical (e.g. gender, patient age, tumour site, clinical presentation) and pathological (tumour size, tumour stage, nodal stage, lymphovascular invasion) features were evaluated using chi square tests, T-tests and Mann-Whitney tests where appropriate.

Results

343 CRC specimens were identified (175 pre-COVID-19, 168 post-COVID-19 slowdown). CRC patients treated surgically post-COVID-19 slowdown had larger tumours (44 mm vs. 35 mm; p = 0.0048) and were more likely to have presented emergently (24% vs .10%; p < 0.001). While there was a trend towards higher tumour stage, nodal stage, and clinical stage, these differences did not reach statistical significance. Other demographic and pathologic variables including patient gender, age, and tumour site were similar between the two cohorts.

Interpretation

The COVID-19 slowdown resulted in a shift in the severity of disease experienced by CRC patients in Ontario. Pandemic planning in the future should consider the long-term consequences to cancer diagnosis and management.
Symptom Persistence Despite Improvement in Cardiopulmonary Health – Insights from longitudinal CMR, CPET and lung function testing post-COVID-19
Authors: Cassar Mark Philip , Tunnicliffe Elizabeth M. , Petousi Nayia , Lewandowski Adam J. , Xie Cheng , Mahmod Masliza , Abd Samat Azlan Helmy , Evans Rachael A. , Brightling Christopher E. , Ho Ling-Pei , Piechnik Stefan K. , Talbot Nick P. , Holdsworth David , Ferreira Vanessa M. , Neubauer Stefan , Raman Betty
Published: August 2021

Background

The longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19.

Methods

Fifty-eight patients and thirty matched controls underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months.

Findings

At 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T1(marker of inflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pVO2) on CPET.

By 6 months, 53% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (−4·3 mls/m2,P=0·005) decreased and RV ejection fraction (+3·2%,P=0·0003) increased. Native T1and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak VO2, although better, were abnormal in patients versus controls. 31% had reduced pVO2secondary to fatigue and submaximal tests. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures.

Interpretation

In patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health.

Funding

NIHR Oxford and Oxford Health BRC, Oxford BHF CRE, UKRI and Wellcome Trust.
Epidemiology of 869,220 varicose vein surgeries over 12 years in Brazil: trends, costs and mortality rate
Authors: Silva Marcela Juliano , Sposato Louzada Andressa Cristina , Alexandrino da Silva Marcelo Fiorelli , Cassino Portugal Maria Fernanda , Teivelis Marcelo Passos , Wolosker Nelson
Published: August 2021

2.

Structured Abstract

Objectives

to assess the total numbers of surgical procedures performed between 2008 and 2019 for the treatment of varicose veins in the Public Health System, which exclusively insures more than 160 million Brazilians, the distribution of surgeries over time, as well as its costs and mortality rates.

Study design

retrospective cross-sectional population-based study

Materials and Methods

public and open data referring to all surgeries to treat chronic venous disease between 2008 and 2019 were extracted from the database of the Brazilian Public Health System.

Results

In total, 869,220 surgeries were performed to treat chronic venous disease in public hospitals and outpatient clinics in Brazil, with an average rate of 4.5 surgeries per 10,000 inhabitants per year. From 2015 on, we observed a slight downward trend in the total number of procedures. The total amount reimbursed by the government was US$ 232,775,518.11. A total of 49 deaths were registered following varicose vein surgery, corresponding to a mortality rate of 0.0056%.

Conclusions

a total of 869,220 surgeries performed to treat chronic venous disease over twelve years, with an overall rate of 4.52 procedures per 10,000 inhabitants per year. The mortality rate was very low, 0.0056%.
ExhauFS: exhaustive search-based feature selection for classification and survival regression
Authors: Nersisyan Stepan , Novosad Victor , Galatenko Alexei , Sokolov Andrey , Bokov Grigoriy , Konovalov Alexander , Alekseev Dmitry , Tonevitsky Alexander
Published: August 2021

Motivation

Feature selection is one of the main techniques used to prevent overfitting in machine learning applications. The most straightforward approach for feature selection is exhaustive search: one can go over all possible feature combinations and pick up the model with the highest accuracy. This method together with its optimizations were actively used in biomedical research, however, publicly available implementation is missing.

Results

We present ExhauFS – the user-friendly command-line implementation of the exhaustive search approach for classification and survival regression. Aside from tool description, we included three application examples in the manuscript to comprehensively review the implemented functionality. First, we executed ExhauFS on a toy cervical cancer dataset to illustrate basic concepts. Then, a multi-cohort microarray and RNA-seq breast cancer datasets were used to construct gene signatures for 5-year recurrence classification. Finally, Cox survival regression models were used to fit isomiR signatures for overall survival prediction for patients with colorectal cancer.

Availability

Source codes and documentation of ExhauFS are available on GitHub: https://github.com/s-a-nersisyan/ExhauFS.

Contact

snersisyan@hse.ru
The heterogeneity of the DNA damage response landscape determines patient outcomes in ovarian cancer
Authors: Walker TDJ , Faraahi ZF , Price MJ , Hawarden A , Waddell CA , Russell B , Jones DM , McCormick A , Gavrielides N , Tyagi S , Woodhouse LC , Whalley B , Roberts C , Crosbie EJ , Edmondson RJ
Published: August 2021

Defective DNA damage response (DDR) pathways allow cancer cells to accrue genomic aberrations and evade normal cellular growth checkpoints. Defective DDR also determines response to chemotherapy. However, the interaction and overlap between the two double strand repair pathways and the three single strand repair pathways is complex, and has remained poorly understood.

Here we show that, in ovarian cancer, a disease hallmarked by chromosomal instability, explant cultures show a range of DDR abrogation patterns. Defective homologous recombination (HR) and non-homologous end joining (NHEJ) are near mutually exclusive with HR deficient (HRD) cells showing increased abrogation of the single strand repair pathways compared to NHEJ defective cells.

When combined with global markers of DNA damage, including mitochondrial membrane functionality and reactive oxygen species burden, the pattern of DDR abrogation allows the construction of DDR signatures which are predictive of bothex vivocytotoxicity, and more importantly, patient outcome.

Significance

Holistic assessment of the DDR is possible, shows improved ability to predict response to chemotherapy over single pathway assessment, and is applicable to a variety of ovarian cancer types. Such an assessment has clinical utility in settings of therapeutic dilemma such as retreatment for relapse.
MapToCleave: high-throughput profiling of microRNA biogenesis in living cells
Authors: Kang Wenjing , Fromm Bastian , Houben Anna J. S. , Høye Eirik , Bezdan Daniela , Arnan Carme , Thrane Kim , Asp Michaela , Johnson Rory B. , Biryukova Inna , Friedländer Marc R.
Published: August 2021

Previous large-scale studies have uncovered many features that determine the processing of microRNA (miRNA) precursors, however, they have been conducted in vitro. Here we introduce MapToCleave, a new method to simultaneously profile processing of thousands of distinct RNA structures in living cells. Our new in cell method captures essentially all the biogenesis features that have been discovered through near two decades of in vitro studies - providing support for both approaches. We find that miRNA precursors with a stable lower basal stem are more efficiently processed and also have higher expression in vivo in tissues from twenty animal species. We systematically compare the importance of known and novel sequence and structural features and test biogenesis of miRNA precursors from ten animal and plant species in human cells. Lastly, we provide evidence that the GHG motif better predicts processing when defined as a structure rather than sequence motif, consistent with recent cryo-EM studies. In summary, we apply a new screening assay in living cells to reveal the importance of lower basal stem stability for miRNA processing and in vivo expression.
Ancestral contributions to contemporary European complex traits
Authors: Marnetto Davide , Pankratov Vasili , Mondal Mayukh , Montinaro Francesco , Pärna Katri , Vallini Leonardo , Molinaro Ludovica , Saag Lehti , Loog Liisa , Montagnese Sara , Costa Rodolfo , Metspalu Mait , Eriksson Anders , Pagani Luca
Published: August 2021

The contemporary European genetic makeup formed in the last 8000 years as the combination of three main genetic components: the local Western Hunter-Gatherers, the incoming Neolithic Farmers from Anatolia and the Bronze Age component from the Pontic Steppes. When meeting into the post-Neolithic European environment, the genetic variants accumulated during their three distinct evolutionary histories mixed and came into contact with new environmental challenges.

Here we investigate how this genetic legacy reflects on the complex trait landscape of contemporary European populations, using the Estonian Biobank as a case study.

For the first time we directly connect the phenotypic information available from biobank samples with the genetic similarity to these ancestral groups, both at a genome-wide level and focusing on genomic regions associated with each of the 27 complex traits we investigated. We also found SNPs connected to pigmentation, cholesterol, sleep, diastolic blood pressure, and body mass index (BMI) to show signals of selection following the post Neolithic admixture events. We recapitulate existing knowledge about pigmentation traits, corroborate the connection between Steppe ancestry and height and highlight novel associations. Among others, we report the contribution of Hunter Gatherer ancestry towards high BMI and low blood cholesterol levels.

Our results show that the ancient components that form the contemporary European genome were differentiated enough to contribute ancestry-specific signatures to the phenotypic variability displayed by contemporary individuals in at least 11 out of 27 of the complex traits investigated here.
A distinct core regulatory module enforces oncogene expression in KMT2A-rearranged leukemia
Authors: Harada Taku , Heshmati Yaser , Kalfon Jérémie , Ferrucio Juliana Xavier , Perez Monika , Ewers Jazmin , Kossenkov Andrew , Ellegast Jana M. , Yi Joanna S. , Bowker Allyson , Zhu Qian , Eagle Kenneth , Dempster Joshua M. , Kugener Guillaume , Wickramasinghe Jayamanna , Herbert Zachary T. , Li Charles H. , Koren Jošt Vrabič , Weinstock David M. , Paralkar Vikram R. , Nabet Behnam , Lin Charles Y. , Dharia Neekesh V. , Stegmaier Kimberly , Orkin Stuart H. , Pimkin Maxim
Published: August 2021

A small set of lineage-restricted transcription factors (TFs), termed core regulatory circuitry (CRC), control cell identity and malignant transformation. Here, we integrated gene dependency, chromatin architecture and TF perturbation datasets to characterize 31 core TFs in acute myeloid leukemia (AML). Contrary to a widely accepted model, we detected a modular CRC structure with hierarchically organized, partially redundant and only sparsely interconnected modules of core TFs controlling distinct genetic programs. Rapid TF degradation followed by measurement of genome-wide transcription rates revealed that core TFs directly regulate dramatically fewer genes than previously assumed. Leukemias carrying KMT2A (MLL) rearrangements depend on the IRF8/MEF2 axis to directly enforce expression of the key oncogenes MYC, HOXA9 and BCL2. Our datasets provide an evolving model of CRC organization in human cells, and a resource for further inquiries into and therapeutic targeting of aberrant transcriptional circuits in cancer.
Selection bias in mutation accumulation
Authors: Wahl Lindi M. , Agashe Deepa
Published: August 2021

Mutation accumulation (MA) experiments, in which de novo mutations are sampled and subsequently characterized, are an essential tool in understanding the processes underlying evolution. In microbial populations, MA protocols typically involve a period of population growth between severe bottlenecks, such that a single individual can form a visible colony. While it has long been appreciated that the action of positive selection during this growth phase cannot be eliminated, it is typically assumed to be negligible. Here, we quantify the effect of both positive and negative selection in MA studies, demonstrating that selective effects can substantially bias the distribution of fitness effects (DFE) and mutation rates estimated from typical MA protocols in microbes. We then present a simple correction for this bias which applies to both beneficial and deleterious mutations, and can be used to correct the observed DFE in multiple environments. Finally, we use simulated MA experiments to illustrate the extent to which the MA-inferred DFE differs from the underlying true DFE, and demonstrate that the proposed correction accurately reconstructs the true DFE over a wide range of scenarios. These results highlight that positive selection during microbial MA experiments is in fact not negligible, but can be corrected to gain a more accurate understanding of fundamental evolutionary parameters.
Three-axis classification of mouse lung mesenchymal cells reveals two populations of myofibroblasts
Authors: del Pilar Odemaris Narvaez , Chen Jichao
Published: August 2021

The mesenchyme consists of heterogeneous cell populations that support neighboring structures and are integral to intercellular signaling. Despite such importance, mesenchymal cell types are poorly defined morphologically and molecularly, lagging behind their counterparts in the epithelial, endothelial, and immune lineages. Leveraging single-cell RNA-seq, three-dimensional imaging, and lineage tracing, we classify the mouse lung mesenchyme into three proximal-distal axes that are associated with the endothelium, epithelium, and interstitium, respectively. From proximal to distal, (1) the vascular axis includes vascular smooth muscle cells and pericytes that transition as arterioles and venules ramify into capillaries; (2) the epithelial axis includes airway smooth muscle cells and two populations of myofibroblasts: ductal myofibroblasts, surrounding alveolar ducts and marked by CDH4, HHIP, and Lgr6, which persist post-alveologenesis, and alveolar myofibroblasts, surrounding alveoli and marked by high expression of PDGFRA, which undergo developmental apoptosis; (3) the interstitial axis, residing between the epithelial and vascular trees and sharing a newly-identified marker MEOX2, includes fibroblasts in the bronchovascular bundle and the alveolar interstitium that are marked by IL33/DNER/PI16 and Wnt2, respectively. Single-cell imaging reveals distinct morphology of each mesenchymal cell population. This classification provides a conceptual and experimental framework applicable to other organs.
Llamanade: an open-source computational pipeline for robust nanobody humanization
Authors: Sang Zhe , Xiang Yufei , Bahar Ivet , Shi Yi
Published: August 2021

Nanobodies (Nbs) have recently emerged as a promising class of antibody fragments for biomedical and therapeutic applications. Despite having marked physicochemical properties, Nbs are derived from camelids and may require “humanization” to improve translational potentials for clinical trials. Here we have systematically analyzed the sequence and structural properties of Nbs based on NGS (next-generation sequencing) databases and high-resolution structures. Our analysis reveals substantial framework diversities and underscores the key differences between Nbs and human Immunoglobulin G (IgG) antibodies. We identified conserved residues that may contribute to enhanced solubility, structural stability, and antigen-binding, providing insights into Nb humanization. Based on big data analysis, we developed “Llamanade’’, a user-friendly, open-source to facilitate rational humanization of Nbs. Using Nb sequence as input, Llamanade provides information on the sequence features, model structures, and optimizes solutions to humanize Nbs. The full analysis for a given Nb takes less than a minute on a local computer. To demonstrate the robustness of this tool, we applied it to successfully humanize a cohort of structurally diverse and highly potent SARS-CoV-2 neutralizing Nbs. Llamanade is freely available and will be easily accessible on a web server to support the development of a rapidly expanding repertoire of therapeutic Nbs into safe and effective trials.

Author Summary

Camelid Nbs are characterized by small size, excellent pharmacological properties and high flexibility in bioengineering for therapeutic development. However, Nbs are “xeno” antibodies, which require “humanization” to improve their translational potential. Currently, there is a lack of systematic investigation of Nbs to rationally guide humanization. No dedicated software has been developed for this purpose. Here, we report the development of Llamanade, an open-source computational pipeline and the first dedicated software to facilitate rational humanization of Nbs.

To subjectively evaluate Llamanade, we used it to humanize a cohort of structurally diverse and ultrapotent antiviral Nbs against SARS-CoV-2. Robust humanization by Llamanade significantly improved the humanness level of Nbs to closely resemble fully human IgGs. Importantly, these highly humanized antiviral Nbs remained excellent solubility and comparably high bioactivities to the non-humanized Nb precursors. We envision that Llamanade will help advance Nb research into therapeutic development.
Quantifying the ongoing epidemic of disability after covid-19 in the UK population aged under 35 years; secondary analysis of the Covid Infection Survey
Authors: Spiers Nicola
Published: August 2021

Web-based survey and anecdotal evidence suggest that many people infected with covid-19 go on to develop long covid (symptoms persisting for more than 12 weeks) despite mild initial disease. There is particular concern that this epidemic is unfolding in the younger population where vaccination rates are low. The Covid Infection Survey (CIS) has recently published estimates of the proportion of people with long covid whose daily activities are affected a little or a lot.

This paper focuses on the population aged under 35 years and uses the term ‘disabling long covid’ to describe those with symptoms lasting more than 12 weeks and daily activities limited a lot. By applying the CIS estimates to confirmed infections, with age breakdown from mid-2020 population estimates, this paper reports a first estimate of the cases of disabling long covid seeded from confirmed covid-19 infections to July 31st 2021.

Results suggest there will approximately 39,000 cases of disabling long covid in those aged under 35 seeded by Covid-19 infections confirmed to July 31st. There is a need for rapid action to prevent Covid-19 infection in the younger population and support those struggling with Long Covid-related disability.
Integrated miRNA/cytokine/chemokine profiling reveals immunopathological step changes associated with COVID-19 severity
Authors: Wilson Julie C. , Kealy David , James Sally R. , Newling Katherine , Jagger Chris , Filbey Kara , Mann Elizabeth R. , Konkel Joanne E. , Menon Madhvi , Knight Sean B. , Simpson Angela ,   CIRCO collaborative group, Grainger John R. , Hussell Tracy , Kaye Paul M. , Signoret Nathalie , Lagos Dimitris
Published: August 2021

Circulating microRNAs (miRNAs) are exceptional mechanism-based correlates of disease, yet their potential remains largely untapped in COVID-19. Here, we determined circulating miRNA and cytokine and chemokine (CC) profiles in 171 blood plasma samples from 58 hospitalised COVID-19 patients. Thirty-two miRNAs were differentially expressed in severe cases when compared to moderate and mild cases. These miRNAs and their predicted targets reflected key COVID-19 features including cell death and hypoxia. Compared to mild cases, moderate and severe cases were characterised by a global decrease in circulating miRNA levels. Partial least squares regression using miRNA and CC measurements allowed for discrimination of severe cases with greater accuracy (87%) than using miRNA or CC levels alone. Correlation analysis revealed severity group-specific associations between CC and miRNA levels. Importantly, the miRNAs that correlated with IL6 and CXCL10, two cardinal COVID-19-associated cytokines, were distinct between severity groups, providing a novel qualitative way to stratify patients with similar levels of proinflammatory cytokines but different disease severity. Integration of miRNA and CC levels with clinical parameters revealed severity-specific signatures associated with clinical hallmarks of COVID-19. Our study highlights the existence of severity-specific circulating CC/miRNA networks, providing insight into COVID-19 pathogenesis and a novel approach for monitoring COVID-19 progression.
Increased circulating cell-free DNA in eosinophilic granulomatosis with polyangiitis: implications for eosinophil extracellular traps and immunothrombosis
Authors: Hashimoto Teppei , Ueki Shigeharu , Kamide Yosuke , Miyabe Yui , Fukuchi Mineyo , Yokoyama Yuichi , Furukawa Tetsuya , Azuma Naoto , Oka Nobuyuki , Takeuchi Hiroki , Kanno Kyoko , Ishida-Yamamoto Akemi , Taniguchi Masami , Hashiramoto Akira , Matsui Kiyoshi
Published: August 2021

Background

Endogenous DNA derived from nuclei or mitochondria is released into the blood circulation as cell-free DNA (cfDNA) following cell damage or death. cfDNA is associated with various pathological conditions; however, its clinical significance in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) remains unclear. This study aimed to evaluate the clinical significance of cfDNA in AAV.

Methods

We enrolled 35 patients with AAV, including 10 with eosinophilic granulomatosis with polyangiitis (EGPA), 13 with microscopic polyangiitis, and 12 with granulomatosis with polyangiitis. Serum cf-nuclear DNA (cf-nDNA) and cf-mitochondrial DNA (cf-mtDNA) levels were measured by quantitative polymerase chain reaction. Tissue samples from EGPA patients were examined by immunofluorescence and transmission electron microscopy. The structure, stability, and platelet adhesion of eosinophil extracellular traps (EETs) were also assessed in vitro.

Results

Serum cf-nDNA and cf-mtDNA levels were significantly higher in AAV than in healthy controls, with the highest levels in EGPA; however, serum DNase activities were comparable among all groups. cf-nDNA and cf-mtDNA decreased after treatment and were associated with disease activity only in EGPA. Blood eosinophil count and plasma D-dimer levels were significantly correlated with cf-nDNA in EGPA and cf-mtDNA. EGPA tissue samples showed lytic eosinophils and EETs in small-vessel thrombi. EETs showed greater stability against DNase than neutrophil extracellular traps and provided a scaffold for platelet adhesion in vitro.

Conclusion

cfDNA was increased in EGPA, associated with disease activity. The presence of DNase-resistant EETs might contribute to the occurrence of immunothrombosis in EGPA.
Clinical characteristics and outcomes of COVID-19 breakthrough infections among vaccinated patients with systemic autoimmune rheumatic diseases
Authors: Cook Claire , Patel Naomi J. , D’Silva Kristin M. , Hsu Tiffany Y-T. , DiIorio Michael , Prisco Lauren , Martin Lily , Vanni Kathleen M.M. , Zaccardelli Alessandra , Todd Derrick J. , Sparks Jeffrey A. , Wallace Zachary S.
Published: August 2021

Objective

To describe the characteristics of COVID-19 vaccine breakthrough infections among systemic autoimmune rheumatic disease (SARD) patients.

Methods

We identified SARDs patients in a large healthcare system with COVID-19 vaccination ≥14 days prior to a positive SARS-CoV-2 molecular test. Details of the patient’s SARD, vaccination status, and COVID-19 infection were extracted.

Results

Of 340 confirmed COVID-19 infections among SARDs patients between December 11th, 2020 (date of first COVID-19 vaccine approval in the US) and July 30th, 2021, we identified 16 breakthrough infections. Seven (44%) received the Pfizer-BioNtech vaccine, five (31%) received the Moderna vaccine, and four (25%) received the Janssen/Johnson & Johnson vaccine. The most common SARDs included rheumatoid arthritis (6, 38%), inflammatory myopathy (3, 19%), and systemic lupus erythematosus (3, 19%). Rituximab (5, 31%), glucocorticoids (4, 25%), and mycophenolate mofetil (4, 25%) were the most frequent treatments. Among the breakthrough infections, 15 (93%) were symptomatic, six (38%) were hospitalized, one (6%) required mechanical ventilation, and two (13%) died.

Conclusions

Symptomatic, including severe, breakthrough infections were observed in SARDs patients; many were on treatments associated with attenuated antibody responses to vaccination. Further studies are needed to determine the rate of breakthrough infection associated with SARD treatments and other features.

Key messages

What is already known about this subject?

Breakthrough infections following COVID-19 vaccination are expected but some patients with systemic autoimmune rheumatic diseases (SARDs) may be at higher risk because of blunted antibody responses to vaccination associated with rheumatic disease treatments and other factors that remain poorly understood.

What does this study add?

We identify and describe 16 COVID-19 vaccine breakthrough infections within the Mass General Brigham system between December 11th, 2020 and June 26th, 2021. The vast majority of cases were symptomatic and two were fatal.

How might this impact on clinical practice or future developments?

This study complements observations regarding the attenuated antibody response to COVID-19 vaccination in patients with SARDs by identifying serious clinical outcomes from breakthrough infections in patients receiving DMARDs that have been reported to have blunted vaccine responses. Our study identifies characteristics of COVID-19 breakthrough infections that may guide the prioritization of booster vaccines and other risk-mitigating strategies in patients with SARDs.
Molecular basis of UHRF1 allosteric activation for synergistic histone modification binding by PI5P
Authors: Mandal Papita , Yerkesh Zhadyra , Kharchenko Vladlena , Zandarashvili Levani , Bensaddek Dalila , Jaremko Lukasz , Black Ben E. , Fischle Wolfgang
Published: August 2021

Chromatin marks are recognized by distinct binding modules many of which are embedded in multidomain proteins or complexes. How the different protein functionalities of complex chromatin modulators are regulated is often unclear. Using a combination of biochemical, biophysical and structural approaches we delineated the regulation of the H3unmodified and H3K9me binding activities of the multidomain UHRF1 protein. The phosphoinositide PI5P interacts with two distant flexible linker regions of UHRF1 in a mode that is dependent on the polar head group and the acyl part of the phospholipid. The associated conformational rearrangements stably position the H3unmodified and H3K9me3 histone recognition modules of UHRF1 for multivalent and synergistic binding of the H3 tail. Our work highlights a novel molecular function for PI5P outside of the context of lipid mono- or bilayers and establishes a molecular paradigm for the allosteric regulation of complex, multidomain chromatin modulators by small cellular molecules.
Preexisting mycobacterial infection modulates Candida albicans-driven pyroptosis
Authors: Bhatt Bharat , Prakhar Praveen , Lohia Gaurav Kumar , Rajmani Raju S. , Balaji Kithiganahalli Narayanaswamy
Published: August 2021

Active tuberculosis patients are at high risk of co-infection with opportunistic fungal pathogen C. albicans. However, the molecular mechanisms that orchestrate pathogenesis of Mycobacterium tuberculosis (Mtb)-C. albicans co-infection remains elusive. In the current study, we utilise a mouse model to demonstrate that Mtb promotes macrophage environment conducive for C. albicans survival. Mtb-dependent PKCζ-WNT signalling axis induces expression of an E3 ubiquitin ligase, COP1. A secondary infection of C. albicans in such Mtb-infected macrophages causes COP1 to mediate the proteasomal degradation of IRF9, a cardinal factor that we identified to arbitrate an inflammatory programmed cell death, pyroptosis. In vivo experiments mimicking a preexisting Mtb infection demonstrate that inhibition of pyroptosis in mice results in increased C. albicans burden and aberrant lung tissue architecture, leading to increased host mortality. Together, our study reveals the crucial role of pyroptosis regulation for manifesting a successful C. albicans-Mtb co-infection.
Identification of key genes and immune infiltration modulated by CPAP in Obstructive sleep apnea by integrated bioinformatics analysis
Authors: Fan Cheng , Huang Shiyuan , Xiang Chunhua , An Tianhui , Song Yi
Published: August 2021

Patients with obstructive sleep apnea (OSA) experience partial or complete upper airway collapses during sleep resulting in nocturnal hypoxia-normoxia cycling. And continuous positive airway pressure (CPAP) is the golden treatment for OSA. Nevertheless, the exact mechanisms of action, especially the transcriptome effect of CPAP on OSA patients, remains elusive. The goal of this study was to evaluate the longitudinal alterations in peripheral blood mononuclear cells transcriptome profiles of OSA patients in order to identify the hub gene and immune response. GSE133601 were downloaded from Gene Expression Omnibus (GEO). We identified black module via weighted gene co-expression network analysis (WGCNA), the genes in which were correlated significantly with the clinical trait of CPAP treatment. Finally, eleven hub genes (TRAV10, SNORA36A, RPL10, OBP2B, IGLV1-40, H2BC8, ESAM, DNASE1L3, CD22, ANK3, ACP3) were traced and used to construct a random forest model to predict therapeutic efficacy of CPAP in OSA with a good performance with AUC of 0.92. We further studied the immune cells infiltration in OSA patients with CIBERSORT, and monocytes were found to be related with the remission of OSA and partially correlated with the hub genes identified. In conclusion, these key genes and immune infiltration may be of great importance in the remission of OSA and related research of these genes may provide a new therapeutic target for OSA in the future.
Intermediary role of lung alveolar type 1 cells in epithelial repair upon Sendai virus infection
Authors: Hernandez Belinda J , Cain Margo P , Flores Jose R , Tuvim Michael J , Dickey Burton F , Chen Jichao
Published: August 2021

The lung epithelium forms the first barrier against respiratory pathogens and noxious chemicals; however, little is known about how >90% of this barrier – made of alveolar type 1 (AT1) cells – responds to injury, in contrast to our accumulating knowledge of epithelial progenitor and stem cells whose importance lies in their ability to restore the barrier. Using Sendai virus to model natural infection in mice, we combine 3D imaging, lineage-tracing, and single-cell genomics to show that AT1 cells have an intermediary role by persisting in areas depleted of alveolar type 2 (AT2) cells, mounting an interferon response, and receding from invading airway cells. Sendai virus infection mobilizes airway cells to form alveolar SOX2+ clusters without differentiating into AT1 or AT2 cells, as shown in influenza models. Intriguingly, large AT2-cell-depleted areas remain covered by AT1 cells, which we name “AT2-less regions”, and are replaced by SOX2+ clusters spreading both basally and luminally around AT1 cell extensions. AT2 cell proliferation and differentiation are largely confined to topologically distal regions – the end of airspace that could be in the periphery or middle of the lung – and form de novo alveolar surface, with limited contribution to in situ repair of AT2-less regions. Time course single-cell RNA-seq and AT1-cell interactome analyses suggest enhanced recognition of AT1 cells by immune cells and altered growth signals. Our comprehensive spatiotemporal and genome-wide study highlights the hitherto unappreciated role of AT1 cells during Sendai virus infection and possibly other injury-repair processes.
A developed combined control method for induction machine drives based on PWM
Authors: Dahmardeh Hassan , Ghanbari Mahmood , Rakhtala Seyed Mehdi
Published: August 2021

Purpose

The purpose of this paper is to develop a combined control (CC) technique based on the direct torque control (DTC) strategy and vector control (VC) method, to improve the overall performance of a three-phase induction machine (TPIM) drives.

Design/methodology/approach

The proposed control scheme includes a table-based DTC strategy in connection with a proportional-integral-sliding mode controller and pulse width modulation switching strategy. The control system has merits of DTC technique such as simple structure, less dependent on machine parameters, fast dynamic response and merits of VC technique such as high accuracy and constant switching frequency.

Findings

To validate the effectiveness of the proposed control system, simulation and experimental studies are carried out for a 0.75 kW TPIM in different operating conditions. The achieved results show the superiority of the proposed method in terms of fast dynamics and simple structure compared to the VC strategy and low speed and torque ripples and constant switching frequency compared to the DTC method.

Originality/value

Compared to the conventional CC strategies, the control law of the proposed method is based on DTC theory and modulation is established based on VC. In other words, the variable switching frequency which is one of the main disadvantages of the conventional CC strategies is rectified using the proposed CC scheme.
Forty five nm CMOS low power multilevel active feedback transimpedance amplifier for optical receivers
Authors: Singh Priya , Niranjan Vandana , Kumar Ashwni
Published: August 2021

Purpose

Recent advancements in the domain of smart communication systems and technologies have led to the augmented developments for very large scale integrated circuit designs in electro-magnetic applications. Increasing demands for low power, compact area and superior figure of merit–oriented circuit designs are the trends of the recent research studies. Hence, to accomplish such applications intended for optical communications, the transimpedance amplifier (TIA) was designed.

Design/methodology/approach

In this research work, the authors present a multi-layer active feedback structure which mainly composes a transimpedance stage and a gain stage followed by a low pass filter. This structure enables to achieve improved input impedance and superior gain. A simplified cascaded amplifier has also been designed in a hierarchical topology to improvise the noise effect further. The proposed TIA has been designed using Taiwan Semiconductor Manufacturing Company 45 nm complementary metal oxide semiconductor technology. Moreover, the thermal noise has been analyzed at −3 dB bandwidth to prove the reduction in thermal noise with increase in frequency for most of the devices used in the designed circuit.

Findings

The proposed differential TIA circuit was found to obtain the transimpedance gain of 50.1 dBO without applying any external bias current which is almost 8% improvised as compared to the conventional circuit. In addition to this, bandwidth achieved was 2.15 GHz along with only 38 W of power consumption, which is reasonably 100 times improvised in comparison of conventional circuit. Hence, the proposed differential TIA is suitable for the low power optical communications applications intended to work on low supply voltage.

Originality/value

The designed work is done by authors in university lab premises and is not copied from anywhere. To the best of the authors’ knowledge, it is 100% original.
Analytic evaluation of facilities performance from the user perspective: case study on a badminton hall
Authors: Shi Wenchao , Lai Joseph H.K. , Chau C.K. , Wong Philip , Edwards David
Published: August 2021

Purpose

The purpose of this study is to identify key performance indicators (KPIs) for badminton halls and, through a case study, illustrate how the facilities performance of a university badminton hall can be evaluated from the user perspective.

Design/methodology/approach

After a desktop literature review, the findings were discussed by a focus group, and the discussion result formed the basis for establishing an analytic hierarchy of facilities performance for the badminton hall. Then, interviews were made with 169 badminton hall users to solicit their perceived facilities’ importance and performance levels of the hall. Using MATLAB, a computer program incorporated with an Analytic Hierarchy Process was devised to compute the importance weights of the performance attributes under assessment. The outcomes were interpreted using an importance-performance evaluation matrix.

Findings

A facilities performance hierarchy, comprising nine KPIs, was established for the badminton hall. The factors influencing the users’ perceptions, the importance and performance levels of the KPIs and the areas of the hall requiring improvements were identified.

Research limitations/implications

Future studies can take a similar approach of this study to develop KPIs and facilities performance hierarchies for other types of sports venues.

Practical implications

The method used to identify the improvements required for the badminton hall can be applied to investigations on other sports facilities.

Originality/value

The methodology of this research was first applied to study a badminton hall – as reported in this paper.
The price-rent dynamics and linkage of urban housing: evidence from Singapore
Authors: Ji Philip Inyeob , Bogati Bhandari Seema
Published: August 2021

Purpose

The aim of this paper is to examine dynamic linkages between price and rent and between property types. Intuition suggests that housing market segments experience different market cycles in response to macroeconomic shocks. However, they may be dynamically interlinked in urban areas because of substitutability. The linkage may even change, if preference weakens for multiple occupancies. A sudden reduction in apartment demand may create repercussions to other housing segments. Past analyses, despite their contributions, are static and do not consider possible linkages between property types. To fill this void, this paper investigates the price-rent dynamics for urban homes by adopting the case of Singapore.

Design/methodology/approach

This paper applies a methodology from Phillips et al. (2015) to Singaporean housing (price and rent) data. Phillips et al. (2015) recently proposed a test for an explosive root in time series data and has spurred several empirical applications in the bubble literature.

Findings

This paper finds for Singapore that the markets were subjected to explosive growth (where rents grew at a higher rate than prices did) during the Global Financial Crisis. Also, the results suggest that rent drives price and that non-landed housing (offices in central areas) leads to other residential housing (non-residential housing) in both price and rent.

Practical implications

Overall, the present findings suggest that rent drives price, while property types are interlinked. Non-landed homes and offices in central areas are the sources of repercussions. Under normal circumstances, rental shocks may be propagated positively from nonlanded housing (central offices) to the other residential (non-residential) property types as the present findings suggest, which enables us to infer that a decrease in non-landed housing (central offices) rent may lead to an increase in rent on other property types because pandemic shocks only shift demand fromone property type to another, unlike typical macroeconomic shocks.

Originality/value

Urban homes are faced with uncertainty arising from the COVID-19 outbreak for which city residents have a stronger incentive to exile to suburbs. Urban life may no longer be attractive because of social distancing and work from home policy. This has implications for urban home demands that are closely linked to urban house price and rent. In the present study, the paper set out to investigate the price-rent and property-type dynamics for urban homes in Singapore.
The intertwined relationship of shadow banking and commercial banks’ deposit growth: evidence from India
Authors: Mohanty Shiba Prasad , Gopalkrishnan Santosh , Mahendra Ashish
Published: August 2021

Purpose

While traditionally it was believed that shadow banking undercuts business from traditional commercial banks, the time has now arrived to examine the various innovative practices used by various shadow banks and non-banking finance companies (NBFCs) to explore various collaboration and competition possibilities. The parallel existence of the traditional and shadow banking systems creates a market environment where both the entities are inter-dependent for growth and development with their edge of advantages and snags. This study aims to investigate the development and growth of deposits in NBFCs and scheduled commercial banks (SCBs) and, through the adoption of innovative practices, highlights possible growth opportunities for both ahead.

Design/methodology/approach

This study uses yearly bank deposit data from 1998 to 2019. This study incorporates univariate autoregressive integrated moving average modeling to predict the future deposit growth of SCBs and NBFCs in India.

Findings

This study concludes that both the entities, i.e. NBFCs and SCBs, will experience deposit growth; however, the proportionate growth of deposits in SCBs will be higher than NBFCs.

Research limitations/implications

This study concludes that the NBFCs will exhibit higher growth in the future. Thus, a strengthened regulatory framework will boost the growth of the NBFCs, providing a safe environment to the investor. Further, as this study primarily considers only deposit-taking NBFCs and commercial banks and a single variable – “deposit” to predict its future growth, it offers a scope for future research to consider and include other kinds of NBFCs like non-deposit taking NBFCs, housing finance companies, micro-finance Institutions and infrastructure finance companies.

Originality/value

A competently regulated financial system of an emerging economy confers tremendous growth opportunities to the financial institutions functioning in the system. Deposits are a significant parameter for the performance of the financial institution; thus, by keeping it as the underlying premise, this study forecasts the future growth in deposits for both the commercial banks and NBFCs. This forecasted growth in deposits for both entities, if analyzed and acted upon appropriately, can, apart from other opportunities for investment, be used to point at directional growth of the economy and the gross domestic product, considering that credit growth is a barometer for economic growth. The scope of this study is limited to NBFCs and SCBs of India and considers only a single variable, i.e. deposit for data analysis and growth forecasting.
Integration of BIM and advanced digital technologies to the end of life decision-making process: a paradigm of future opportunities
Authors: Abruzzini Aurora , Abrishami Sepehr
Published: August 2021

Purpose

At the end of a building’s lifecycle, there are several limitations to the decision-making process (DMP). There is a lack of data available from the building’s history, the difficulty in assessing the condition of a building and the variety of stakeholders’ needs that have to be satisfied. The purpose of this paper is to answer the question: how would end-of-life (EOL) DMP change when buildings will have been digitally built? The answer will be illustrated through a conceptual framework.

Design/methodology/approach

A qualitative analysis of the existing literature has been performed to identify the elements within building information modelling (BIM) and advanced digital technologies that could be of support to the DMP. The findings have been collected and summarised in a conceptual framework that has been validated and enhanced through online interviews with industry experts.

Findings

The enhanced framework has identified that BIM technology would bring the benefit of providing the initial digital data source, from which machine learning and data analytics would then extract the relevant data needed to measure accurately the criteria during the analysis of the EOL options put on the table.

Originality/value

The findings of this research could contribute to developing the software modules making the bridge between BIM and machine learning technologies, to implement them in the EOL DMP.