bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonged inhibitory effect of repeated period tibial nerve stimulation on the micturition reflex in the rat
Authors: Zeng Jiawen , Zeng Shaohua , Jiang Chonghe , Lindström Sivert
Published: July 2020

Background

The aims of this study was determine if stimulation of tibial nerve afferents could induce a prolonged modulation of the micturition reflex in the rats.

Methods

Fifteen female Sprague Dawley rats (250-350 g) were fully decorticated and paralysed for the study. Tibial nerve stimulation (TNS) was delivered by inserting two pairs of needle electrodes close to the nerves at the level of the medial malleolus. Constant flow cystometries (0.07 ml/min) at about 10 min interval were performed and the micturition threshold volume (MTV) was recorded and used as the dependent variable. After 4 – 5 stable control recordings, the tibial nerves of both sides were stimulated continuously for 5 min at 10 Hz, 3 times threshold for α-motor axons. Six times of same stimulation were applied repeatedly with an interval of 5 min between the stimulations. The mean MTV was compiled from several cystometries in each half hour before the TNS and during, after 6 periods TNS.

Results

During the experiment, all the animals survived in a good condition with reasonably stable micturition reflexes, a significant increase in MTV was revealed after TNS. The best effect (mean 178%) occurred during the first 30 min after 6 periods of stimulation. This clear threshold increase remained for at least 5 h.

Conclusions

A prolonged increase in MTV was demonstrated by a short periods of TNS repeatedly. This post stimulation modulatory effects of micturition reflex would provide a theoretical explanation for the clinical beneficial effect of TNS in patients with overactive bladder (OAB).
Curcumin combined with Glu-GNPs enhancing radiosensitivity of transplanted tumor of MDA-MB-231-luc cells in nude mice
Authors: Li Mengjie , Guo Tingting , Wu Yujian , Lin Jiayi , Yang Ke , Hu Chenxia
Published: July 2020

Breast cancer is the first cause of cancer death in women all over the world. And the morbidity of breast cancer has been increasing in recent years. Nowadays, the treatment of breast cancer is still a problem. Radiotherapy resistance is one of the important factors leading to poor prognosis of clinical treatment. Curcumin, a plant polyphenol from Curcuma longa, has antitumor activity and inhibition of tumor recurrence and metastasis. However, the influence of curcumin on radiosensitivity of breast carcinoma xenografts, the synergistic effect and possible mechanism of curcumin and Glucose-Gold nanoparticles (Glu-GNPs) in nude mice in vivo need to be further explored. The model of transplanted tumor in nude mice was established and sensitized by intravenous injection of curcumin and Glu-GNPs. The results showed that curcumin can significantly inhibit the growth of tumor, and has no obvious effect on the body weight of nude mice, and Curcumin, Glu-GNPs and X-ray irradiation treatment alone or in combination could reduce the expression ofVEGFandHSP90mRNA and protein compared with model group in tumor tissue. The inhibition of irradiation resistance may be related to inhibiting the synthesis ofVEGFandHSP90. This study suggested that curcumin and Glu-GNPs have the radiosensitization effect in vivo, which provides an experimental basis for the clinical development of green radiosensitizers.
Analysis of the transcriptome and DNA methylome in response to acute and recurrent low glucose in human primary astrocytes
Authors: Potter Paul G Weightman , Washer Sam , Jeffries Aaron R , Holley Janet E , Gutowski Nick J , Dempster Emma , Beall Craig
Published: July 2020

Aims/hypothesis

Recurrent hypoglycaemia (RH) is a major side-effect of intensive insulin therapy for people with diabetes. Changes in hypoglycaemia sensing by the brain contribute to the development of impaired counterregulatory responses to and awareness of hypoglycaemia. Little is known about the intrinsic changes in human astrocytes in response to acute and recurrent low glucose (RLG) exposure.

Methods

Human primary astrocytes (HPA) were exposed to zero, one, three or four bouts of low glucose (0.1 mmol/l) for three hours per day for four days to mimic RH. On the fourth day, DNA and RNA were collected. Differential gene expression and ontology analyses were performed using DESeq2 and GOseq respectively. DNA methylation was assessed using the Infinium MethylationEPIC BeadChip platform.

Results

24 differentially expressed genes (DEGs) were detected (after correction for multiple comparisons). One bout of low glucose exposure had the largest effect on gene expression. Pathway analyses revealed that endoplasmic-reticulum (ER) stress-related genes such asHSPA5,XBP1, andMANF, involved in the unfolded protein response (UPR), were all significantly increased following LG exposure, which was diminished following RLG. There was little correlation between differentially methylated positions and changes in gene expression yet the number of bouts of LG exposure produced distinct methylation signatures.

Conclusions/interpretation

These data suggest that exposure of human astrocytes to transient LG triggers activation of genes involved in the UPR linked to endoplasmic reticulum (ER) stress. Following RLG, the activation of UPR related genes was diminished, suggesting attenuated ER stress. This may be mediated by metabolic adaptations to better preserve intracellular and/or ER ATP levels, but this requires further investigation.
Single species RNA purification with DNA nanoswitches
Authors: Zhou Lifeng , Cavaliere Cassandra , Hayden Andrew , Dey Paromita , Mao Song , Chandrasekaran Arun Richard , Sheng Jia , Dey Bijan K. , Halvorsen Ken
Published: July 2020

We report a novel method to purify individual RNA species using programmable DNA nanoswitches to facilitate RNA capture, release, and isolation. We validate sequence-based purification of microRNA, rRNA, and an mRNA fragment from total RNA, demonstrate multiplexing with two different RNA species, and show an application with downstream LC/MS analysis to identify RNA modifications. The simplicity, low cost, and low sample requirements of our method make it suitable for easy adoption.
Optoribogenetic control of regulatory RNA molecules
Authors: Pilsl Sebastian , Morgan Charles , Choukeife Moujab , Möglich Andreas , Mayer Günter
Published: July 2020

Short regulatory RNA molecules underpin gene expression and govern cellular state and physiology. To establish a novel layer of control over these processes, we generated chimeric regulatory RNAs that interact reversibly and light-dependently with the light-oxygen-voltage photoreceptor PAL. By harnessing this interaction, the function of micro RNAs (miRs) and short hairpin (sh) RNAs in mammalian cells can be regulated in spatiotemporally precise manner. The underlying strategy is generic and can be adapted to near-arbitrary target sequences. Owing to full genetic encodability, it establishes unprecedented optoribogenetic control of cell state and physiology. The method stands to facilitate the non-invasive, reversible and spatiotemporally resolved study of regulatory RNAs and protein function in cellular and organismal environments.
Genes Encoding ACE2, TMPRSS2 and Related Proteins Mediating SARS-CoV-2 Viral Entry are Upregulated with Age in Human Cardiomyocytes
Authors: Robinson Emma L. , Alkass Kanar , Bergmann Olaf , Maguire Janet J. , Roderick H. Llewelyn , Davenport Anthony P.
Published: July 2020

Age is an independent risk factor for adverse outcome in patients following COVID-19 infection. We hypothesised that differential expression of genes encoding proteins proposed to be required for entry of SARS-Cov-2 in aged compared to younger cardiomyocytes might contribute to the susceptibility of older individuals to COVID-19-associated cardiovascular complications.

We generated strand-specific RNA-sequencing libraries from RNA isolated from flow-sorted cardiomyocyte nuclei from left ventricular tissue. RNASeq data were compared between five young (19-25yr) and five older (63-78yr) Caucasian males who had not been on medication or exhibited evidence of cardiovascular disease post-mortem.

Expression of relevant genes encodingACE2, TMPRSS2, TMPRS11D, TMPRS11E, FURIN, CTSL, CTSBandB0AT1/SLC6A19were upregulated in aged cardiomyocytes and the combined relative cardiomyocyte expression of these genes correlated positively with age. Genes encoding proteins in the RAAS and interferon/interleukin pathways were also upregulated such asACE, AGTR1, MAS1andIL6R.

Our results highlight SARS-CoV-2 related genes that have higher expression in aged compared with young adult cardiomyocytes. These data may inform studies using selective enzyme inhibitors/antagonists, available as experimental compounds or clinically approved drugs e.g. remdesivir that has recently been rapidly accepted for compassionate use, to further understand the contribution of these pathways in human cardiomyocytes to disease outcome in COVID-19 patients.
Dimeric prion protein ligand activates Adgrg6 but does not rescue myelinopathy of PrP-deficient mice
Authors: Henzi Anna , Senatore Assunta , Lakkaraju Asvin KK , Scheckel Claudia , Mühle Jonas , Reimann Regina , Sorce Silvia , Schertler Gebhard , Toyka Klaus V , Aguzzi Adriano
Published: July 2020

The adhesion G-protein coupled receptor Adgrg6 (formerly Gpr126) is instrumental in the development, maintenance and repair of peripheral nervous system myelin. The prion protein (PrP) is a potent activator of Adgrg6 and could be used as a potential therapeutic agent in treating peripheral demyelinating and dysmyelinating diseases. We designed a dimeric Fc-fusion protein comprising the myelinotrophic domain of PrP (FT2Fc), which activated Adgrg6 in vitro and exhibited favorable pharmacokinetic properties for in vivo treatment of peripheral neuropathies. While chronic FT2Fc treatment elicited specific transcriptomic changes in the sciatic nerves of PrP knockout mice, no amelioration of the peripheral demyelinating neuropathy was detected. Instead, RNA sequencing of sciatic nerves revealed downregulation of cytoskeletal and sarcomere genes, akin to the gene expression changes seen in myopathic skeletal muscle of PrP overexpressing mice. These results call for caution when devising myelinotrophic therapies based on PrP-derived Adgrg6 ligands. While our treatment approach was not successful, Adgrg6 remains an attractive therapeutic target to be addressed in other disease models or by using different biologically active Adgrg6 ligands.

Summary blurb

A dimeric prion protein ligand activates Adgrg6 but fails to induce pro-myelination signaling upon chronic treatment in a mouse model of peripheral demyelination.
Loss of Ubiquitin Ligase STUB1 Amplifies IFNγ-R1/JAK1 Signaling and Sensitizes Tumors to IFNγ
Authors: Apriamashvili Georgi , Vredevoogd David W. , Krijgsman Oscar , Bleijerveld Onno B. , Ligtenberg Maarten A. , de Bruijn Beaunelle , Boshuizen Julia , Altimari Daniela D’Empaire , Visser Nils L. , Londino James D. , Altelaar Maarten , Peeper Daniel S.
Published: July 2020

Despite the success of immune checkpoint blockade (ICB) most patients fail to respond durably, in part owing to reduced interferon gamma (IFNγ) sensitivity. Thus, elevating tumor IFNγ-receptor 1 (IFNγ-R1) expression to enhance IFNγ-mediated cytotoxicity is of potential clinical interest. Here, we show that increased IFNγ-R1 expression sensitizes tumors to IFNγ-mediated killing. To unveil the largely undefined mechanism governing IFNγ-R1 expression, we performed a genome-wide CRISPR/Cas9 screen for suppressors of its cell surface abundance. We uncovered STUB1 as key mediator of proteasomal degradation of the IFNγ-R1/JAK1 complex. STUB1 inactivation amplified IFNγ signaling, thereby sensitizing to cytotoxic T cells, but also inducing PD-L1. STUB1 loss in a rational combination with PD-1 blockade strongly inhibited melanomasin vivo. Clinically corroborating these results, aSTUB1-KO gene signature was strongly associated with anti-PD-1 response. These results uncover STUB1 as pivotal regulator of IFNγ tumor signaling and provide a rationale for its inhibition combined with anti-PD-1.
Beware of White Matter Hyperintensities Causing Systematic Errors in Grey Matter Segmentations!
Authors: Dadar Mahsa , Potvin Olivier , Camicioli Richard , Duchesne Simon ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: July 2020

Introduction

Volumetric estimates of subcortical and cortical structures, extracted from T1-weighted MRIs, are widely used in many clinical and research applications. Here, we investigate the impact of the presence of white matter hyperintensities (WMHs) onFreeSurfergrey matter (GM) structure volumes and its possible bias on functional relationships.

Methods

T1-weighted images from 1077 participants (4321 timepoints) from the Alzheimer’s Disease Neuroimaging Initiative were processed withFreeSurferversion 6.0.0. WMHs were segmented using a previously validated algorithm on either T2-weighted or Fluid-attenuated inversion recovery (FLAIR) images. Mixed effects models were used to assess the relationships between overlapping WMHs and GM structure volumes and overal WMH burden, as well as to investigate whether such overlaps impact associations with age, diagnosis, and cognitive performance.

Results

Participants with higher WMH volumes had higher overalps with GM volumes of bilateral caudate, cerebral cortex, putamen, thalamus, pallidum, and accumbens areas (P < 0.0001). When not corrected for WMHs, caudate volumes increased with age (P < 0.0001) and were not different between cognitively healthy individuals and age-matched probable Alzheimer’s disease patients. After correcting for WMHs, caudate volumes decreased with age (P < 0.0001), and Alzheimer’s disease patients had lower caudate volumes than cognitively healthy individuals (P < 0.01). Uncorrected caudate volume was not associated with ADAS13 scores, whereas corrected lower caudate volumes were significantly associated with poorer cognitive performance (P < 0.0001).

Conclusions

Presence of WMHs leads to systematic inaccuracies in GM segmentations, particularly for the caudate, which can also change clinical associations. While specifically measured for theFreesurfertoolkit, this problem likely affects other algorithms.
Divergent strategies to reduce stomatal pore index during water deficit in perennial angiosperms
Authors: Mano Noel Anthony , Lopez Santiago Franco , Mickelbart Michael V.
Published: July 2020

⍰ Modulation of stomatal development may be an acclimation response to low water availability. However, stomatal development plasticity has been assessed in very few species.

⍰ We quantified leaf anatomy traits, including stomatal index (SI), density (SD), size (SS), and pore index (SPI), in response to water-deficit stress in river birch (Betula nigraL.), eastern redbud (Cercis canadensisL.), and silver maple (Acer saccharinumL.).

⍰ Birch and redbud, but not maple, had reduced SPI in response to water deficit. The mechanism by which SPI reduction occurred (via SD or SS) varied among species and with severity of water stress. Despite reduced SPI in birch and redbud, anatomical changes were relatively small and had a minor to no effect on the theoretical maximum stomatal conductance. Furthermore, gas-exchange rates were equivalent to well-watered plants following media re-irrigation.

⍰ In some tree species, stomatal development is downregulated in response to water deficit conditions. Stomatal development plasticity is facilitated by smaller or fewer stomata, depending upon the species and the intensity of the stress. Water-deficit-induced plasticity in stomatal development is species-specific, likely due to species adaptation to ecological niches.
Pomegranate: 2D segmentation and 3D reconstruction for fission yeast and other radially symmetric cells
Authors: Baybay Erod Keaton , Esposito Eric , Hauf Silke
Published: July 2020

Three-dimensional (3D) segmentation of cells in microscopy images is crucial to accurately capture signals that extend across optical sections. Using brightfield images for segmentation has the advantage of being minimally phototoxic and leaving all other channels available for signals of interest. However, brightfield images only readily provide information for two-dimensional (2D) segmentation. In radially symmetric cells, such as fission yeast and many bacteria, this 2D segmentation can be computationally extruded into the third dimension. However, current methods typically make the simplifying assumption that cells are straight rods. Here, we report Pomegranate, a pipeline that performs the extrusion into 3D using spheres placed along the topological skeletons of the 2D-segmented regions. The diameter of these spheres adapts to the cell diameter at each position. Thus, Pomegranate accurately represents radially symmetric cells in 3D even if cell diameter varies and regardless of whether a cell is straight, bent or curved. We have tested Pomegranate on fission yeast and demonstrate its ability to 3D segment wild-type cells as well as classical size and shape mutants. The pipeline is available as macro for the open-source image analysis software Fiji/ImageJ. 2D segmentations created within or outside Pomegranate can serve as input, thus making this a valuable extension to the image analysis portfolio already available for fission yeast and other radially symmetric cell types.
Evolutionary dynamics of sex-biased genes expressed in cricket brains and gonads
Authors: Whittle Carrie A. , Kulkarni Arpita , Extavour Cassandra G.
Published: July 2020

Sex-biased gene expression, particularly sex-biased expression in the gonad, has been linked to rates of protein sequence evolution (nonsynonymous to synonymous substitutions, dN/dS) in animals. However, in insects, sex-biased expression studies remain centered on a few holometabolous species, and moreover, other major tissue types such as the brain remain underexplored. Here, we studied sex-biased gene expression and protein evolution in a hemimetabolous insect, the cricketGryllus bimaculatus. We generated novel male and female RNA-seq data for two sexual tissue types, the gonad and somatic reproductive system, and for two core components of the nervous system, the brain and ventral nerve cord. From a genome-wide analysis, we report several core findings. Firstly, testis-biased genes had accelerated evolution, as compared to ovary-biased and unbiased genes, which was associated with positive selection events. Secondly, while sex-biased brain genes were much less common than for the gonad, they exhibited a striking tendency for rapid protein evolution, an effect that was stronger for the female than male brain. Further, some sex-biased brain genes were linked to sexual functions and mating behaviors, which we suggest may have accelerated their evolution via sexual selection. Thirdly, a tendency for narrow cross-tissue expression breadth, suggesting low pleiotropy, was observed for sex-biased brain genes, suggesting relaxed purifying selection, which we speculate may allow enhanced freedom to evolve adaptive protein functional changes. The findings of rapid evolution of testis-biased genes and male and female-biased brain genes are discussed with respect to pleiotropy, positive selection, and the mating biology of this cricket.
Tau forms oligomeric complexes on microtubules that are distinct from pathological oligomers in disease
Authors: Gyparaki M. T. , Arab A. , Sorokina E. M. , Santiago-Ruiz A. N. , Bohrer C. H. , Xiao J. , Lakadamyali M.
Published: July 2020

Tau is a microtubule-associated protein, which promotes neuronal microtubule assembly and stability. Accumulation of tau into insoluble aggregates known as neurofibrillary tangles (NFTs) is a pathological hallmark of several neurodegenerative diseases. The current hypothesis is that small, soluble oligomeric tau species preceding NFT formation cause toxicity. However, thus far visualizing the spatial distribution of tau monomers and oligomers inside cells under physiological or pathological conditions has not been possible. Here, using single molecule localization microscopy (SMLM), we show that,in vivo, tau forms small oligomers on microtubules under physiological conditions. These physiological oligomers are distinct from those found in cells exhibiting tau aggregation and could be pre-cursors of aggregated tau in pathology. Further, using an unsupervised shape classification algorithm that we developed, we show that different tau phosphorylation states are associated with distinct tau aggregate species. Our work elucidates tau’s nanoscale composition under physiological and pathological conditionsin vivo.
Ultra-accurate Microbial Amplicon Sequencing Directly from Complex Samples with Synthetic Long Reads
Authors: Callahan Benjamin J , Grinevich Dmitry , Thakur Siddhartha , Balamotis Michael A , Yehezkel Tuval Ben
Published: July 2020

Out of the many pathogenic bacterial species that are known, only a fraction are readily identifiable directly from a complex microbial community using standard next generation DNA sequencing technology. Long-read sequencing offers the potential to identify a wider range of species and to differentiate between strains within a species, but attaining sufficient accuracy in complex metagenomes remains a challenge. Here, we describe and analytically validate LoopSeq, a commercially-available synthetic long-read (SLR) sequencing technology that generates highly-accurate long reads from standard short reads. LoopSeq reads are sufficiently long and accurate to identify microbial genes and species directly from complex samples. LoopSeq applied to full-length 16S rRNA genes from known strains in a microbial community perfectly recovered the full diversity of full-length exact sequence variants in a known microbial community. Full-length LoopSeq reads had a per-base error rate of 0.005%, which exceeds the accuracy reported for other long-read sequencing technologies. 18S-ITS and genomic sequencing of fungal and bacterial isolates confirmed that LoopSeq sequencing maintains that accuracy for reads up to 6 kilobases in length. Analysis of rinsate from retail meat samples demonstrated that LoopSeq full-length 16S rRNA synthetic long-reads could accurately classify organisms down to the species level, and could differentiate between different strains within species identified by the CDC as potential foodborne pathogens. The order-of-magnitude improvement in both length and accuracy over standard Illumina amplicon sequencing achieved with LoopSeq enables accurate species-level and strain identification from complex and low-biomass microbiome samples. The ability to generate accurate and long microbiome sequencing reads using standard short read sequencers will accelerate the building of quality microbial sequence databases and removes a significant hurdle on the path to precision microbial genomics.
Notch controls arterialization by regulating the cell cycle and not differentiation
Authors: Luo Wen , Garcia-Gonzalez Irene , Fernandez-Chacon Macarena , Casquero-Garcia Veronica , Benedito Rui
Published: July 2020

Arteries are thought to be formed by the induction of a highly conserved arterial genetic program in a subset of vessels experiencing an increase in pulsatile and oxygenated blood flow. Both VEGF and Notch signalling have been shown to be essential for the initial steps of arterial specification. Here, we combined inducible genetic mosaics and transcriptomics to modulate and understand the function of these signalling pathways on cell proliferation, arterial-venous differentiation and mobilization. We observed that endothelial cells with high VEGF or Notch signalling are not genetically pre-determined and can form both arteries and veins. Importantly, cells completely lacking the Notch-Rbpj transcriptional activator complex can form arteries when the Myc-dependent metabolic and cell-cycle activity is suppressed. Thus, arterial development does not require the induction of a Notch-dependent arterial differentiation program, but rather the timely suppression of the endothelial metabolism and cell-cycle, a process preceding arterial mobilization and complete differentiation.
Joint Detection of Serum IgM/IgG Antibody is An Important Key to Clinical Diagnosis of SARS-COV-2 Infection
Authors: Hu Fang , Shang Xiaoling , Chen Meizhou , Zhang Changliang
Published: July 2020

Background

This study was aimed to investigate the application of SARS- COV-2 IgM and IgG antibodies in diagnosis of COVID-19 infection.

Method

This study enrolled a total of 178 patients at Huangshi Central Hospital from January to February, 2020. Among them, 68 patients were SARS-COV-2 infected confirmed with nucleic acid test (NAT) and CT imaging. 9 patients were in the suspected group (NAT negative) with fever and other respiratory symptoms. 101 patients were in the control group with other diseases and negative to SARS-COV-2 infection. After serum samples were collected, SARS-COV-2 IgG and IgM antibodies were tested by chemiluminescence immunoassay (CLIA) for all patients.

Results

The specificity of serum IgM and IgG antibodies to SARS-COV-2 were 99.01% (100/101) and 96.04% (97/101) respectively, and the sensitivity were 88.24% (60/68) and 97.06% (66/68) respectively. The combined detection rate of SARS-COV-2 IgM and IgG antibodies were 98.53% (67/68).

Conclusion

Combined detection of serum SARS-COV-2 IgM and IgG antibodies had better sensitivity compared with single IgM or IgG test, which can be used as an important diagnostic tool for SARS-COV-2 infection and a screening tool of potential SARS-COV-2 carriers in clinics, hospitals and accredited scientific laboratory.
Accuracy of online symptom checkers and the potential impact on service utilisation
Authors: Ceney Adam , Tolond Stephanie , Glowinski Andrzej , Marks Ben , Swift Simon , Palser Tom
Published: July 2020

Objectives

The aims of this study are firstly to investigate the diagnostic and triage performance of symptom checkers, secondly to assess their potential impact on healthcare utilisation and thirdly to investigate for variation in performance between systems.

Setting

Publicly available symptom checkers

Participants

Publicly available symptom-checkers were identified. A standardised set of 50 clinical vignettes was developed and systematically run through each system by a non-clinical researcher.

Primary and secondary outcome measures

System accuracy was assessed by measuring the percentage of times the correct diagnosis was a) listed first, b) within the top five diagnoses listed and c) listed at all. The safety of the disposition advice was assessed by comparing it with national guidelines for each vignette.

Results

Twelve tools were identified and included. Mean diagnostic accuracy of the systems was poor, with the correct diagnosis being listed first on 37.7% (Range 22.2 to 72.0%) of occasions and present in the top five diagnoses on 51.0% (Range 22.2 to 84.0%). 51.0% of systems suggested additional resource utilisation above that recommended by national guidelines (range 18.0% to 61.2%). Both diagnostic accuracy and appropriate resource recommendation varied substantially between systems.

Conclusions

There is wide variation in performance between available symptom checkers and overall performance is significantly below what would be accepted in any other medical field, though some do achieve a good level of accuracy and safety of disposition. External validation and regulation are urgently required to ensure these public facing tools are safe.

Strengths and Limitations

Data collection was undertaken by non-clinically trained staff to replicate patient behaviour and there was random sampling to test the inter-rater reliability

Clinical vignettes were agreed by a clinical team consisting of a GP, a pharmacist and a hospital emergency care consultant

Current UK guidelines were used to assess service utilisation. Where symptom checkers were developed outside of the UK the disposition advice may be unlikely to be aligned due to different jurisdictions

This research was a limited indirect study on the variety of terms and language patients might use in their interactions with these systems

There was no assessment of how a clinician would diagnose and triage a patient presenting with the vignette symptoms
High excess mortality during the COVID-19 outbreak in Stockholm Region areas with young and socially vulnerable populations
Authors: Calderón-Larrañaga Amaia , Vetrano Davide L , Rizzuto Debora , Bellander Tom , Fratiglioni Laura , Dekhtyar Serhiy
Published: July 2020

Background

We aimed to describe the distribution of excess mortality (EM) during the first weeks of the COVID-19 outbreak in the Stockholm Region, Sweden, according to individual age and sex, and the sociodemographic context

Methods

Weekly all-cause mortality data were obtained from Statistics Sweden for the period 01/01/2015 to 17/05/2020. EM during the first 20 weeks of 2020 was estimated by comparing observed mortality rates with expected mortality rates during the five previous years (N=2,379,792). EM variation by socioeconomic status (tertiles of income, education, Swedish-born, gainful employment) and age distribution (share of 70+ year-old persons) was explored based on Demographic Statistics Area (DeSO) data.

Findings

An EM was first detected during the week of March 23-29 2020. During the peaking week of the epidemic (6-12 April 2020), an EM of 160% was observed: 211% in 80+ year-old women; 179% in 80+ year-old men. During the same week, the highest EM was observed for DeSOs with lowest income (171%), lowest education (162%), lowest share of Swedish-born (178%), and lowest share of gainfully employed (174%). There was a 1.2 to 1.7-fold increase in EM between those areas with a higher vs. lower proportion of young people.

Interpretation

Living in areas with lower socioeconomic status and younger populations is linked to COVID-19 EM. These conditions might have facilitated the viral spread. Our findings add to the well-known biological vulnerability linked to increasing age, the relevance of the sociodemographic context when estimating the individual risk to COVID-19.

Funding

None.
Atypical Presentations of COVID-19 in Care Home Residents presenting to Secondary Care: A UK Single Centre Study
Authors: Rawle Mark James , Bertfield Deborah Lee , Brill Simon Edward
Published: July 2020

Purpose

The United Kingdom (UK) care home population has experienced high mortality during the COVID-19 pandemic. Atypical presentations of COVID-19 are being reported in older adults and may pose difficulties for early isolation and treatment, particularly in institutional care settings. We aimed to characterise the presenting symptoms and associated mortality of COVID-19 in older adults, with a focus on care home residents and older adults living in the community.

Methods

This was a retrospective cohort study of consecutive inpatients over 80 years old hospitalised with PCR confirmed COVID-19 between 10th March 2020 and 8th April 2020. Symptoms at presentation, including those associated with frailty, were analysed. Differences between community dwelling and care home residents, and associations with mortality, were assessed using between-group comparisons and logistic regression.

Results

Care home residents were less likely to experience cough (46.9% vs 72.9%, p=0.002) but more likely to present with delirium (51.6% vs 31.4%, p=0.018), particularly hypoactive delirium (40.6% vs 24.3%, p=0.043). Mortality was more likely in the very frail (OR 1.25, 95% CI 1.00, 1.58, p=0.049) and those presenting with anorexia (OR 3.20, 95% CI 1.21, 10.09, p=0.028). There were no differences in either mortality or length of stay between those admitted from care homes and community dwelling older adults.

Conclusion

COVID-19 in those over 80 does not always present with typical symptoms, particularly in those admitted from institutional care. These individuals have a reduced incidence of cough and increased hypoactive delirium. Individuals presenting atypically, especially with anorexia, have higher mortality.
Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients
Authors: Aschenbrenner Anna C. , Mouktaroudi Maria , Krämer Benjamin , Antonakos Nikolaos , Oestreich Marie , Gkizeli Konstantina , Nuesch-Germano Melanie , Saridaki Maria , Bonaguro Lorenzo , Reusch Nico , Baßler Kevin , Doulou Sarandia , Knoll Rainer , Pecht Tal , Kapellos Theodore S. , Rovina Nikoletta , Kröger Charlotte , Herbert Miriam , Holsten Lisa , Horne Arik , Gemünd Ioanna D. , Agrawal Shobhit , Dahm Kilian , Uelft Martina van , Drews Anna , Lenkeit Lena , Bruse Niklas , Gerretsen Jelle , Gierlich Jannik , Becker Matthias , Händler Kristian , Kraut Michael , Theis Heidi , Mengiste Simachew , Domenico Elena De , Schulte-Schrepping Jonas , Seep Lea , Raabe Jan , Hoffmeister Christoph , ToVinh Michael , Keitel Verena , Rieke Gereon , Talevi Valentina , Aziz N. Ahmad , Pickkers Peter , van de Veerdonk Frank , Netea Mihai G. , Schultze Joachim L. , Kox Matthijs , Breteler Monique M.B. , Nattermann Jacob , Koutsoukou Antonia , Giamarellos-Bourboulis Evangelos J. , Ulas Thomas ,   German COVID-19 Omics Initiative (DeCOI)
Published: July 2020

The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases calls for a better characterization and understanding of the changes in the immune system. Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 11 COVID-19 patients. Comparison of COVID-19 blood transcriptomes with those of a collection of over 2,800 samples derived from 11 different viral infections, inflammatory diseases and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host.
Reconstructing the early global dynamics of under-ascertained COVID-19 cases and infections
Authors: Russell Timothy W. , Golding Nick , Hellewell Joel , Abbott Sam , Wright Lawrence , Pearson Carl A B , Zandvoort Kevin van , Jarvis Christopher I , Gibbs Hamish , Liu Yang , Eggo Rosalind M. , Edmunds W. John , Kucharski Adam J.
Published: July 2020

Background

Asymptomatic or subclinical SARS-CoV-2 infections are often unreported, which means that confirmed case counts may not accurately reflect underlying epidemic dynamics. Understanding the level of ascertainment (the ratio of confirmed symptomatic cases to the true number of symptomatic individuals) and undetected epidemic progression is crucial to informing COVID-19 response planning, including the introduction and relaxation of control measures. Estimating case ascertainment over time allows for accurate estimates of specific outcomes such as seroprevalence, which is essential for planning control measures.

Methods

Using reported data on COVID-19 cases and fatalities globally, we estimated the proportion of symptomatic cases (i.e. any person with any of fever >= 37.5°C, cough, shortness of breath, sudden onset of anosmia, ageusia or dysgeusia illness) that were reported in 210 countries and territories, given those countries had experienced more than ten deaths. We used published estimates of the baseline case fatality ratio (CFR), which was adjusted for delays and under-ascertainment, then calculated the ratio of this baseline CFR to an estimated local delay-adjusted CFR to estimate the level of under-ascertainment in a particular location. We then fit a Bayesian Gaussian process model to estimate the temporal pattern of under-ascertainment.

Results

Based on reported cases and deaths, we estimated that, during March 2020, the median percentage of symptomatic cases detected across the 84 countries which experienced more than ten deaths ranged from 2.4% (Bangladesh) to 100% (Chile). Across the ten countries with the highest number of total confirmed cases as of 6th July 2020, we estimated that the peak number of symptomatic cases ranged from 1.4 times (Chile) to 18 times (France) larger than reported. Comparing our model with national and regional seroprevalence data where available, we find that our estimates are consistent with observed values. Finally, we estimated seroprevalence for each country. As of the 7th June, our seroprevalence estimates range from 0% (many countries) to 13% (95% CrI: 5.6% – 24%) (Belgium).

Conclusions

We found substantial under-ascertainment of symptomatic cases, particularly at the peak of the first wave of the SARS-CoV-2 pandemic, in many countries. Reported case counts will therefore likely underestimate the rate of outbreak growth initially and underestimate the decline in the later stages of an epidemic. Although there was considerable under-reporting in many locations, our estimates were consistent with emerging serological data, suggesting that the proportion of each country’s population infected with SARS-CoV-2 worldwide is generally low.

Funding

Wellcome Trust, Bill & Melinda Gates Foundation, DFID, NIHR, GCRF, ARC.
Modeling reductions in SARS-CoV-2 transmission and hospital burden achieved by prioritizing testing using a clinical prediction rule
Authors: Reimer Jody R. , Ahmed Sharia M. , Brintz Benjamin , Shah Rashmee U. , Keegan Lindsay T. , Ferrari Matthew J. , Leung Daniel T.
Published: July 2020

Prompt identification of cases is critical for slowing the spread of COVID-19. However, many areas have faced diagnostic testing shortages, requiring difficult decisions to be made regarding who receives a test, without knowing the implications of those decisions on population-level transmission dynamics. Clinical prediction rules (CPRs) are commonly used tools to guide clinical decisions. We used data from electronic health records to develop a parsimonious 5-variable CPR to identify those who are most likely to test positive, and found that its application to prioritize testing increases the proportion of those testing positive in settings of limited testing capacity. To consider the implications of these gains in daily case detection on the population level, we incorporated testing using the CPR into a compartmentalized disease transmission model. We found that prioritized testing led to a delayed and lowered infection peak (i.e. “flattens the curve”), with the greatest impact at lower values of the effective reproductive number (such as with concurrent social distancing measures), and when higher proportions of infectious persons seek testing. Additionally, prioritized testing resulted in reductions in overall infections as well as hospital and intensive care unit (ICU) burden. In conclusion, we present a novel approach to evidence-based allocation of limited diagnostic capacity, to achieve public health goals for COVID-19.

One Sentence Summary

A clinical prediction rule to prioritize SARS-CoV-2 testing improves daily case detection, flattens and delays the curve, and reduces hospital burden.
Single-cell analysis of human embryos reveals diverse patterns of aneuploidy and mosaicism
Authors: Starostik Margaret R. , Sosina Olukayode A. , McCoy Rajiv C.
Published: July 2020

Less than half of human zygotes survive to birth, primarily due to aneuploidies of meiotic or mitotic origin. Mitotic errors generate chromosomal mosaicism, defined by multiple cell lineages with distinct chromosome complements. The incidence and impacts of mosaicism in human embryos remain controversial, with most previous studies based on bulk DNA assays or comparisons of multiple biopsies of few embryonic cells. Single-cell genomic data provide an opportunity to quantify mosaicism on an embryo-wide scale. To this end, we extended an approach to infer aneuploidies based on dosage-associated changes in gene expression by integrating signatures of allelic imbalance. We applied this method to published single-cell RNA sequencing data from 74 human embryos, spanning the morula to blastocyst stages. Our analysis revealed widespread mosaic aneuploidies, with 59 of 74 (80%) embryos harboring at least one putative aneuploid cell (1% FDR). By clustering copy number calls, we reconstructed histories of chromosome segregation, inferring that 55 (74%) embryos possessed mitotic aneuploidies and 23 (31%) embryos possessed meiotic aneuploidies. We found no significant enrichment of aneuploid cells in the trophectoderm compared to the inner cell mass, although we do detect such enrichment in data from later postimplantation stages. Finally, we observed that aneuploid cells up-regulate immune response genes and down-regulate genes involved in proliferation, metabolism, and protein processing, consistent with stress responses documented in other stages and systems. Together, our work provides a high-resolution view of aneuploidy in preimplantation embryos, and supports the conclusion that low-level mosaicism is a common feature of early human development.
Health care service quality: a journey so far
Authors: Upadhyai Raghav , Upadhyai Neha , Jain Arvind Kumar , Roy Hiranmoy , Pant Vimal
Published: July 2020

Purpose

Health care service is a widely researched area. Several established models and instruments measuring health care service quality (HCSQ) are available in the published academic literature. The objective of this article is to summarize this vast pool of available knowledge under the themes of HCSQ, its determinants and measurement strategies.

Design/methodology/approach

Sixty-three available published studies in peer reviewed journal combed in EBSCO and Google Scholar database have been examined and presented in exemplary literature review.

Findings

The findings have been segregated under the themes of HCSQ, its dimensions and determinants. It can be deduced from the findings that in spite of health care being a professional service, the user defined service quality takes center stage.

Originality/value

Rather than the seeker of care, the authors call for further research by taking a dyadic view of professional exchanges and including providers' perspectives of care in service quality evaluations as well.
Analyzing barriers and strategies for implementing Lean Six Sigma in the context of Indian SMEs
Authors: Gaikwad Sandesh Kanhu , Paul Ananna , Moktadir Md. Abdul , Paul Sanjoy Kumar , Chowdhury Priyabrata
Published: July 2020

Purpose

The purpose of this study is to investigate the barriers for implementing Lean Six Sigma (LSS) in small and medium-sized enterprises (SMEs) and present a framework that provides prioritized strategies to overcome the barriers.

Design/methodology/approach

The barriers and strategies are identified via a comprehensive literature review and validated by industry experts. The study uses the fuzzy Technique for Order of Preference by Similarity to Ideal Solution (fuzzy TOPSIS) to analyze the barriers and strategies for determining the prioritized list of strategies.

Findings

The findings reveal that there are sixteen barriers to LSS implementation in Indian SMEs. To overcome these barriers, this study reveals twelve strategies. The analysis shows that “effective management” is the most crucial strategy to overcome the barriers for implementing LSS in Indian SMEs.

Research limitations/implications

This research guides SMEs practitioners to efficiently and effectively implement LSS, which, in turn, can enhance the performance of SMEs.

Originality/value

This study contributes to the literature by integrating the strategies with the barriers for implementing LSS in Indian SMEs. Besides, this study provides the prioritized list of strategies to overcome the barriers for implementing LSS in Indian SMEs.
Violent behaviour on construction sites: structural equation modelling of its impact on unsafe behaviour using partial least squares
Authors: Adinyira Emmanuel , Manu Patrick , Agyekum Kofi , Mahamadu Abdul-Majeed , Olomolaiye Paul Olaniyi
Published: July 2020

Purpose

Work on construction sites involves individuals with diverse character, temperament,age, physical strength, culture, religion and experience level. A good number of these individuals are also alleged to involve themselves in substance and alcohol abuse due to the physically demanding nature of their work. These could promote the prevalence of violence on construction sites which could in turn affect safety on construction sites. However, there is a lack of empirical insight into the effect of violent behaviour and unsafe behaviour on construction sites. This study therefore pioneers an empirical inquiry into the relationship between violent behaviour and unsafe behaviour on construction sites.

Design/methodology/approach

Seventeen violent behaviours and 15 unsafe behaviours were measured on 12 construction sites among 305 respondents using a structured questionnaire. A total of 207 valid questionnaire responses were collected from site workers. Partial least square–structural equation modelling (PLS-SEM) technique was used to examine the relationship between violent behaviour and unsafe behaviour.

Findings

The results indicate that there is a significant positive relationship between violent behaviour and unsafe behaviour on construction sites.

Originality/value

The findings from this study provide valuable insight into a less investigated dimension of the problem of construction site safety management. A focus on attitudinal issues such as how workers relate toward others and toward self should be an important consideration in safety improvement interventions on construction sites.
The passport nightmare: business process analysis in public service
Authors: Ramirez-Nafarrate Adrian , López-Hernández Carlos Eduardo
Published: July 2020

Learning outcomes

Students should be able to: identify the elements of business processes; analyze efficiency measures; identify and define causes of poor efficiency in business process; analyze the results of a simulation model; propose process redesign alternatives based on the analysis; and acknowledge the challenges for improving public service processes.

Case overview/synopsis

The process to get a passport seems to be very simple, but Jose Hernandez, a Manufacturing Plant Director, has had bad experiences the past three times he has visited the passport office. He and his family have spent more than 3 h to get the passport for his little daughter, Maria. In this case, the authors illustrate the process analysis performed by Jose to find effective and efficient solutions to the problems that he found. The case study guides students through the analysis of a business process in public service from the perspective of the users. The students participating in the case analysis will not only learn to diagnose and describe the process but also to redesign it to achieve significant improvements. Furthermore, the students will realize that adding more resources to the process may not solve the fundamental issues, but analytical and creative skills are needed. In addition, the teaching notes provide a discussion about the existing challenges to improve public service processes.

Complexity academic level

Management and engineering undergraduate programs, operations management and business process design in Master of Business Administration programs.

Supplementary materials

Teaching Notes are available for educators only.

Subject code

CSS 9: Operations and Logistics.