bluuebunny/crossref_metadata_2025 huggingface dataset:
Mice derived from in vitro αMEM-cultured preimplantation embryos exhibit postprandial hyperglycemia and higher inflammatory gene expression in peripheral leukocytes
Authors: Ishiyama Shiori , Kimura Mayu , Umihira Nodoka , Matsumoto Sachi , Takahashi Atsushi , Nakagawa Takao , Wakayama Teruhiko , Kishigami Satoshi , Mochizuki Kazuki
Published: February 2021

We examined whether peripheral leukocytes of mice derived from in vitro αMEM-cultured embryos and exhibiting type 2 diabetes had higher expression of inflammatory-related genes associated with the development of atherosclerosis. Also, we examined the impact of a barley diet on inflammatory gene expression. Adult mice were produced by embryo transfer, after culturing two-cell embryos for 48 h in either α minimal essential media (α-MEM) or potassium simplex optimized medium control media. Mice were fed either a barley or rice diet for 10 weeks. Postprandial blood glucose and mRNA levels of several inflammatory genes, including Tnfa and Nox2, in blood leukocytes were significantly higher in MEM mice fed a rice diet compared with control mice. Barley intake reduced expression of S100a8 and Nox2. In summary, MEM mice exhibited postprandial hyperglycemia and peripheral leukocytes with higher expression of genes related to the development of atherosclerosis, and barley intake reduced some gene expression.
Subtype-GAN: a deep learning approach for integrative cancer subtyping of multi-omics data
Authors: Yang Hai , Chen Rui , Li Dongdong , Wang Zhe
Published: February 2021

Motivation

The discovery of cancer subtyping can help explore cancer pathogenesis, determine clinical actionability in treatment, and improve patients' survival rates. However, due to the diversity and complexity of multi-omics data, it is still challenging to develop integrated clustering algorithms for tumor molecular subtyping.

Results

We propose Subtype-GAN, a deep adversarial learning approach based on the multiple-input multiple-output neural network to model the complex omics data accurately. With the latent variables extracted from the neural network, Subtype-GAN uses consensus clustering and the Gaussian Mixture model to identify tumor samples' molecular subtypes. Compared with other state-of-the-art subtyping approaches, Subtype-GAN achieved outstanding performance on the benchmark datasets consisting of ∼4000 TCGA tumors from 10 types of cancer. We found that on the comparison dataset, the clustering scheme of Subtype-GAN is not always similar to that of the deep learning method AE but is identical to that of NEMO, MCCA, VAE and other excellent approaches. Finally, we applied Subtype-GAN to the BRCA dataset and automatically obtained the number of subtypes and the subtype labels of 1031 BRCA tumors. Through the detailed analysis, we found that the identified subtypes are clinically meaningful and show distinct patterns in the feature space, demonstrating the practicality of Subtype-GAN.

Availabilityand implementation

The source codes, the clustering results of Subtype-GAN across the benchmark datasets are available at https://github.com/haiyang1986/Subtype-GAN.

Supplementary information

Supplementary data are available at Bioinformatics online.
Graph contextualized attention network for predicting synthetic lethality in human cancers
Authors: Long Yahui , Wu Min , Liu Yong , Zheng Jie , Kwoh Chee Keong , Luo Jiawei , Li Xiaoli
Published: February 2021

Motivation

Synthetic Lethality (SL) plays an increasingly critical role in the targeted anticancer therapeutics. In addition, identifying SL interactions can create opportunities to selectively kill cancer cells without harming normal cells. Given the high cost of wet-lab experiments, in silico prediction of SL interactions as an alternative can be a rapid and cost-effective way to guide the experimental screening of candidate SL pairs. Several matrix factorization-based methods have recently been proposed for human SL prediction. However, they are limited in capturing the dependencies of neighbors. In addition, it is also highly challenging to make accurate predictions for new genes without any known SL partners.

Results

In this work, we propose a novel graph contextualized attention network named GCATSL to learn gene representations for SL prediction. First, we leverage different data sources to construct multiple feature graphs for genes, which serve as the feature inputs for our GCATSL method. Second, for each feature graph, we design node-level attention mechanism to effectively capture the importance of local and global neighbors and learn local and global representations for the nodes, respectively. We further exploit multi-layer perceptron (MLP) to aggregate the original features with the local and global representations and then derive the feature-specific representations. Third, to derive the final representations, we design feature-level attention to integrate feature-specific representations by taking the importance of different feature graphs into account. Extensive experimental results on three datasets under different settings demonstrated that our GCATSL model outperforms 14 state-of-the-art methods consistently. In addition, case studies further validated the effectiveness of our proposed model in identifying novel SL pairs.

Availabilityand implementation

Python codes and dataset are freely available on GitHub (https://github.com/longyahui/GCATSL) and Zenodo (https://zenodo.org/record/4522679) under the MIT license.

Supplementary information

Supplementary data are available at Bioinformatics online.
The extracellular matrix as modifier of neuroinflammation and remyelination in multiple sclerosis
Authors: Ghorbani Samira , Yong V Wee
Published: February 2021

Remyelination failure contributes to axonal loss and progression of disability in multiple sclerosis. The failed repair process could be due to ongoing toxic neuroinflammation and to an inhibitory lesion microenvironment that prevents recruitment and/or differentiation of oligodendrocyte progenitor cells into myelin-forming oligodendrocytes. The extracellular matrix molecules deposited into lesions provide both an altered microenvironment that inhibits oligodendrocyte progenitor cells, and a fuel that exacerbates inflammatory responses within lesions. In this review, we discuss the extracellular matrix and where its molecules are normally distributed in an uninjured adult brain, specifically at the basement membranes of cerebral vessels, in perineuronal nets that surround the soma of certain populations of neurons, and in interstitial matrix between neural cells. We then highlight the deposition of different extracellular matrix members in multiple sclerosis lesions, including chondroitin sulphate proteoglycans, collagens, laminins, fibronectin, fibrinogen, thrombospondin and others. We consider reasons behind changes in extracellular matrix components in multiple sclerosis lesions, mainly due to deposition by cells such as reactive astrocytes and microglia/macrophages. We next discuss the consequences of an altered extracellular matrix in multiple sclerosis lesions. Besides impairing oligodendrocyte recruitment, many of the extracellular matrix components elevated in multiple sclerosis lesions are pro-inflammatory and they enhance inflammatory processes through several mechanisms. However, molecules such as thrombospondin-1 may counter inflammatory processes, and laminins appear to favour repair. Overall, we emphasize the crosstalk between the extracellular matrix, immune responses and remyelination in modulating lesions for recovery or worsening. Finally, we review potential therapeutic approaches to target extracellular matrix components to reduce detrimental neuroinflammation and to promote recruitment and maturation of oligodendrocyte lineage cells to enhance remyelination.
Haemophagocytic lymphohistiocytosis in a patient with left ventricular assist device
Authors: Ergi Defne Güneş , Dorken Gallastegi Ander , Arslan Eren , Kahraman Ümit
Published: February 2021

Left ventricular assist devices provide circulatory support to heart failure patients while awaiting a suitable donor heart. However, with their increased duration of therapy, complications are seen frequently. Although coagulation disorders (bleeding and thrombosis) are the most common complications, infection is also a major complication associated with significant morbidity. We report a case of a 53-year-old male with a left ventricular assist device who presented with driveline infection. He subsequently developed pancytopenia and was diagnosed with haemophagocytosis. Immediate treatment with intravenous immunoglobulin and methylprednisolone was started. His blood cell count returned to normal levels and the patient became eligible for heart transplantation again. Our case represents the rare occurrence of haemophagocytosis in a patient, which, if unnoticed, could lead to fatal consequences.
Clinical implications of late-onset right ventricular failure after implantation of a continuous-flow left ventricular assist device as bridge to transplantation
Authors: Ruiz-Cano Maria J , Ramazyan Lylit , Schramm Renné , Lauenroth Volker , Paluszkiewicz Lech , Rojas Sebastian , Gummert Jan , Morshuis Michiel
Published: February 2021

OBJECTIVES

The development of late-onset right ventricular failure (LoRVF) that occurs months after a continuous-flow left ventricular assist device (LVAD) is implanted is a clinical problem that warrants investigation. Our goal was to study the incidence, clinical manifestations and prognosis of LoRVF in a population of patients who received an LVAD as bridge to transplantation.

METHODS

Data were analysed from 97 consecutive patients who received an LVAD as bridge to transplantation and underwent a right heart catheterization at least 3 months after receiving an LVAD implantation. LoRVF was defined if both haemodynamic criteria of a central venous pressure >16 mmHg and a cardiac index <2.3 l/min/m2 were present. Clinical and echocardiographic variables, hospitalizations for heart failure and survival were compared between patients with and without LoRVF.

RESULTS

LoRVF was diagnosed in 13% of patients after a median time of 11 months. Patients with LoRVF presented preoperative worse right ventricular (RV) dilatation and severe tricuspid regurgitation. LORVF was also associated with postoperative RV dilatation, moderate to severe tricuspid regurgitation and lower tricuspid annular plane systolic excursion. LoRVF resulted in increased brain natriuretic peptide levels and the need for diuretics, lower haemoglobin levels and a higher rate of atrial fibrillation and gastrointestinal bleeding. The rate of hospitalizations for heart failure in patients with LoRVF was 46%, and 15% required an urgent transplantation due to refractory RV failure. LoRVF decreased global survival and survival free from hospitalizations for heart failure (P < 0.0001).

CONCLUSIONS

LoRVF after the implantation of an LVAD as bridge to transplantation is associated with higher morbidity and lower survival. The results suggest that the routine use of a right heart catheterization and transthoracic echocardiography may contribute to an early diagnosis before further severe complications due to refractory RV failure might occur.

ID number of the IRB approval

AZ-2019-521 on 10 July 2019.
Cardioprotection with esmolol-based cardioplegia for non-infarcted and infarcted rat hearts
Authors: Veitinger Alexander B , Komguem Audrey , Assling-Simon Lena , Heep Martina , Schipke Julia , Mühlfeld Christian , Niemann Bernd , Grieshaber Philippe , Boengler Kerstin , Böning Andreas
Published: February 2021

OBJECTIVES

Esmolol-based cardioplegic arrest offers better cardioprotection than crystalloid cardioplegia but has been compared experimentally with blood cardioplegia only once. We investigated the influence of esmolol crystalloid cardioplegia (ECCP), esmolol blood cardioplegia (EBCP) and Calafiore blood cardioplegia (Cala) on cardiac function, metabolism and infarct size in non-infarcted and infarcted isolated rat hearts.

METHODS

Two studies were performed: (i) the hearts were subjected to a 90-min cardioplegic arrest with ECCP, EBCP or Cala and (ii) a regional myocardial infarction was created 30 min before a 90-min cardioplegic arrest. Left ventricular peak developed pressure (LVpdP), velocity of contractility (dLVP/dtmax), velocity of relaxation over time (dLVP/dtmin), heart rate and coronary flow were recorded. In addition, the metabolic parameters were analysed. The infarct size was determined by planimetry, and the myocardial damage was determined by electron microscopy.

RESULTS

In non-infarcted hearts, cardiac function was better preserved with ECCP than with EBCP or Cala relative to baseline values (LVpdP: 100 ± 28% vs 86 ± 11% vs 57 ± 7%; P = 0.002). Infarcted hearts showed similar haemodynamic recovery for ECCP, EBCP and Cala (LVpdP: 85 ± 46% vs 89 ± 55% vs 56 ± 26%; P = 0.30). The lactate production with EBCP was lower than with ECCP (0.6 ± 0.7 vs 1.4 ± 0.5 μmol/min; P = 0.017). The myocardial infarct size and (ECCP vs EBCP vs Cala: 16 ± 7% vs 15 ± 9% vs 24 ± 13%; P = 0.21) the ultrastructural preservation was similar in all groups.

CONCLUSIONS

In non-infarcted rat hearts, esmolol-based cardioplegia, particularly ECCP, offers better myocardial protection than Calafiore. After an acute myocardial infarction, cardioprotection with esmolol-based cardioplegia is similar to that with Calafiore.
Long-term survival after surgical aortic valve replacement in patients aged 80 years and over
Authors: Malvindi Pietro Giorgio , Luthra Suvitesh , Giritharan Suresh , Kowalewski Mariusz , Ohri Sunil
Published: February 2021

OBJECTIVES

Surgical aortic valve replacement can be safely performed in people aged 80 years and older with early benefits on both symptomatic and prognostic ground. While new approaches are advocated to treat this elderly and frail population, data on long-term outcomes are not available.

METHODS

We conducted a retrospective analysis of 1870 patients aged 80 years and over who underwent first time surgical aortic valve replacement during the period 2000–2019. The Kaplan–Meier method was used to calculate survival and comparisons among groups were performed by log-rank test. Cox analysis was used to determine the independent risk factors for late mortality.

RESULTS

The patients’ mean age was 84 years and 53% were male. Isolated aortic valve replacement was performed in 42% of the patients, and coronary artery bypass grafting (n = 956), mitral valve (n = 94) or aortic surgery (n = 69) were associated in the remaining cases. One hundred eighty-one patients (8%) sustained at least 1 postoperative complication (reopening for bleeding or tamponade 3%, renal replacement therapy 3%, new cerebral stroke 1.5%). In-hospital mortality was 3.2% in the overall population (60/1870) and 2.2% after isolated aortic valve replacement (18/790). Survival was 90%, 66%, 31% and 14% at 1, 5, 10 and 15 years, respectively, and was similar to the expected survival of a sex- and age-matched population (log-rank P = 0.96). A complicated postoperative course was an independent risk factor for mortality during the follow-up [hazard ratio 1.32 (1.03, 1.68), P = 0.026].

CONCLUSIONS

Surgical aortic valve replacement can be performed with an acceptable early mortality rate and provides excellent long-term survival in people aged 80 years and older.
NEWS2 to assess suspected COVID-19 in the community: a service evaluation of a primary care assessment centre
Authors: Zaman Imran , Beevers Zachary C R , Ahmed Ridwan , Lasserson Daniel , Knight Thomas
Published: February 2021

Background

Primary care has played a central role in the community response to the coronavirus disease-19 (COVID-19) pandemic. The use of the National Early Warning Score 2 (NEWS2) has been advocated as a tool to guide escalation decisions in the community. The performance of this tool applied in this context is unclear.

Aim

To evaluate the process of escalation of care to the hospital within a primary care assessment centre (PCAC) designed to assess patients with suspected COVID-19 in the community.

Design and setting

A retrospective service evaluation of all adult patients assessed between 30 March and 22 April 2020 within a COVID-19 primary care assessment centre within Sandwell West Birmingham CCG.

Method

A database of patient demographics, healthcare interactions and physiological observations was constructed. NEWS2 and CRB65 scores were calculated retrospectively. The proportion of patients escalated was within risk groups defined by NHSE guidelines in place during the evaluation period was determined.

Results

A total of 150 patients were identified. Following assessment 13.3% (n = 20) patients were deemed to require escalation. The proportion of patients escalated with a NEWS2 greater than or equal to 3 was 46.9% (95% CI 30.8–63.6%). The proportion of patients escalated to secondary care using NHSE defined risk thresholds was 0% in the green group, 22% (n = 4) in the amber group, and 81.3% (n = 13) in the red group.

Conclusion

Clinical decisions to escalate care to the hospital did not follow initial guidance written for the COVID-19 outbreak but were demonstrated to be safe.
Why genetic selection to reduce the prevalence of infectious diseases is way more promising than currently believed
Authors: Hulst Andries D , de Jong Mart C M , Bijma Piter
Published: February 2021

Genetic selection for improved disease resistance is an important part of strategies to combat infectious diseases in agriculture. Quantitative genetic analyses of binary disease status, however, indicate low heritability for most diseases, which restricts the rate of genetic reduction in disease prevalence. Moreover, the common liability threshold model suggests that eradication of an infectious disease via genetic selection is impossible because the observed-scale heritability goes to zero when the prevalence approaches zero. From infectious disease epidemiology, however, we know that eradication of infectious diseases is possible, both in theory and practice, because of positive feedback mechanisms leading to the phenomenon known as herd immunity. The common quantitative genetic models, however, ignore these feedback mechanisms. Here, we integrate quantitative genetic analysis of binary disease status with epidemiological models of transmission, aiming to identify the potential response to selection for reducing the prevalence of endemic infectious diseases. The results show that typical heritability values of binary disease status correspond to a very substantial genetic variation in disease susceptibility among individuals. Moreover, our results show that eradication of infectious diseases by genetic selection is possible in principle. These findings strongly disagree with predictions based on common quantitative genetic models, which ignore the positive feedback effects that occur when reducing the transmission of infectious diseases. Those feedback effects are a specific kind of Indirect Genetic Effects; they contribute substantially to the response to selection and the development of herd immunity (i.e., an effective reproduction ratio less than one).
Protective effects of antidepressant citalopram against abnormal APP processing and amyloid beta-induced mitochondrial dynamics, biogenesis, mitophagy and synaptic toxicities in Alzheimer’s disease
Authors: Reddy Arubala P , Yin Xiangling , Sawant Neha , Reddy P Hemachandra
Published: February 2021

The purpose of this study is to study the neuroprotective role of selective serotonin reuptake inhibitor (SSRI), citalopram, against Alzheimer’s disease (AD). Multiple SSRIs, including citalopram, are reported to treat patients with depression, anxiety and AD. However, their protective cellular mechanisms have not been studied completely. In the current study, we investigated the protective role of citalopram against impaired mitochondrial dynamics, defective mitochondrial biogenesis, defective mitophagy and synaptic dysfunction in immortalized mouse primary hippocampal cells (HT22) expressing mutant APP (SWI/IND) mutations. Using quantitative RT-PCR, immunoblotting, biochemical methods and transmission electron microscopy methods, we assessed mutant full-length APP/C-terminal fragments and Aβ levels and mRNA and protein levels of mitochondrial dynamics, biogenesis, mitophagy and synaptic genes in mAPP-HT22 cells and mAPP-HT22 cells treated with citalopram. Increased levels of mRNA levels of mitochondrial fission genes, decreased levels of fusion biogenesis, autophagy, mitophagy and synaptic genes were found in mAPP-HT22 cells relative to WT-HT22 cells. However, mAPP-HT22 cells treated with citalopram compared to mAPP-HT22 cells revealed reduced levels of the mitochondrial fission genes, increased fusion, biogenesis, autophagy, mitophagy and synaptic genes. Our protein data agree with mRNA levels. Transmission electron microscopy revealed significantly increased mitochondrial numbers and reduced mitochondrial length in mAPP-HT22 cells; these were reversed in citalopram-treated mAPP-HT22 cells. Cell survival rates were increased in citalopram-treated mAPP-HT22 relative to citalopram-untreated mAPP-HT22. Further, mAPP and C-terminal fragments werealso reduced in citalopram-treated cells. These findings suggest that citalopram reduces mutant APP and Aβ and mitochondrial toxicities and may have a protective role of mutant APP and Aβ-induced injuries in patients with depression, anxiety and AD.
Exergetic performance analysis of low GWP alternative refrigerants for R404A in a refrigeration system
Authors: Altinkaynak Mehmet
Published: February 2021

According to the regulation of European Union laws in 2014, it was inevitable to switch to low global warming potential (GWP) fluids in the refrigeration systems where the R404A working fluid is currently used. The GWP of R404A is very high, and the potential for ozone depletion is zero. In this study, energetic and exergetic performance assessment of a theoretical refrigeration system was carried out for R404 refrigerant and its alternatives, comparatively. The analyses were made for R448A, R449A, R452A and R404A. The results of the analysis were presented separately in the tables and graphs. According to the results, the cooling system working with R448A exhibited the best performance with a coefficient of performance (COP) value of 2.467 within the alternatives of R404A followed by R449A and R452A, where the COP values were calculated as 2.419 and 2.313, respectively. In addition, the exergy efficiencies of the system were calculated as 20.62%, 20.22% and 19.33% for R448A, R449A and R452A, respectively. For the base calculations made for R404A, the COP of the system was estimated as 2.477, where the exergy efficiency was 20.71%. Under the same operating conditions, the total exergy destruction rates for R404A, R448A, R449A and R452A working fluids were found to be 3.201 kW, 3.217 kW, 3.298 kW and 3.488 kW, respectively. Furthermore, parametric analyses were carried out in order to investigate the effects of different system parameters such as evaporator and condenser temperature.
Product Matrix Processes With Symplectic and Orthogonal Invariance via Symmetric Functions
Authors: Ahn Andrew , Strahov Eugene
Published: February 2021

We apply symmetric function theory to study random processes formed by singular values of products of truncations of Haar distributed symplectic and orthogonal matrices. These product matrix processes are degenerations of Macdonald processes introduced by Borodin and Corwin. Through this connection, we obtain explicit formulae for the distribution of singular values of a deterministic matrix multiplied by a truncated Haar orthogonal or symplectic matrix under conditions where the latter factor acts as a rank $1$ perturbation. Consequently, we generalize the recent Kieburg–Kuijlaars–Stivigny formula for the joint singular value density of a product of truncated unitary matrices to symplectic and orthogonal symmetry classes. Specializing to products of two symplectic matrices with a rank $1$ perturbative factor, we show that the squared singular values form a Pfaffian point process.
Extreme Morphology, Functional Trade-offs, and Evolutionary Dynamics in a Clade of Open-Ocean Fishes (Perciformes: Bramidae)
Authors: Gilbert Michelle C , Conith Andrew J , Lerose Catherine S , Moyer Joshua K , Huskey Steve H , Albertson R Craig
Published: February 2021

Synopsis

When novel or extreme morphologies arise, they are oft met with the burden of functional trade-offs in other aspects of anatomy, which may limit phenotypic diversification and make particular adaptive peaks inaccessible. Bramids (Perciformes: Bramidae) comprise a small family of 20 extant species of fishes, which are distributed throughout pelagic waters worldwide. Within the Bramidae, the fanfishes (Pteraclis and Pterycombus) differ morphologically from the generally stout, laterally compressed species that typify the family. Instead, Pteraclis and Pterycombus exhibit extreme anterior positioning of the dorsal fin onto the craniofacial skeleton. Consequently, they possess fin and skull anatomies that are radically different from other bramid species. Here, we investigate the anatomy, development, and evolution of the Bramidae to test the hypothesis that morphological innovations come at functional (proximate) and evolutionary (ultimate) costs. Addressing proximate effects, we find that the development of an exaggerated dorsal fin is associated with neurocrania modified to accommodate an anterior expansion of the dorsal fin. This occurs via reduced development of the supraoccipital crest (SOC), providing a broad surface area on the skull for insertion of the dorsal fin musculature. While these anatomical shifts are presumably associated with enhanced maneuverability in fanfishes, they are also predicted to result in compromised suction feeding, possibly limiting the mechanisms of feeding in this group. Phylogenetic analyses suggest craniofacial and fin morphologies of fanfishes evolved rapidly and are evolutionarily correlated across bramids. Furthermore, fanfishes exhibit a similar rate of lineage diversification as the rest of the Bramidae, lending little support for the prediction that exaggerated medial fins are associated with phylogenetic constraint. Our phylogeny places fanfishes at the base of the Bramidae and suggests that nonfanfish bramids have reduced medial fins and re-evolved SOCs. These observations suggest that the evolution of novel fin morphologies in basal species has led to the phylogenetic coupling of head and fin shape, possibly predisposing the entire family to a limited range of feeding. Thus, the evolution of extreme morphologies may have carryover effects, even after the morphology is lost, limiting ecological diversification of lineages.
The Most Influential Woman in Tech
Authors: Hamilton Johanna
Published: February 2021

Anne-Marie Imafidon MBE is Computer Weekly's most influential woman in tech 2020. She talks to Johanna Hamilton AMBCS about awards, equality and why sometimes it's great to have compliments about your laptop and shoes.
Becoming a UX Pro
Authors: Burgar Vanessa
Published: February 2021

User experience (UX) is a rapidly growing specialism, essential to the design of modern technology. Vanessa Burgar DipHE MSc QTS CITP discusses what knowledge is needed for successful practice and considers how can we provide education for aspiring UX professionals that is fit-for-purpose and strengthens professional identity.
BCS Virtual Festival of Digital Skills
Authors: Penketh Claire
Published: February 2021

BCS successfully delivers virtual conference with the theme of nurturing digital skills to aid economic recovery post-COVID. Claire Penketh reports.
How on Earth Can You Help The World?
Authors: Basu Dalim
Published: February 2021

There is a shortage of skilled IT professionals and the need will increase hugely in the future, writes Dalim Basu FBCS, Chairman of BCS London Central and North London.
10 Things You Need to Know About Data in 2021
Authors: Barnett Vanessa
Published: February 2021

Vanessa Barnett, Technology and Data Partner at Keystone Law, scans the data regulation horizon to warn of what's to come in the year ahead.
Why is it Governance so Important?
Authors: Taylor Paul
Published: February 2021

Organisations need to implement suitable governance to ensure technology platforms are suitably controlled and managed, argues freelance consultant, Paul Taylor MBCS.
How Covid-19 Changed The Future
Authors: Madhavan Naveen
Published: February 2021

Naveen Madhavan PhD MBCS, Senior Product Specialist (Pathology) at the NHS Wales Informatics Service, assesses how COVID-19 has changed our perceptions of the workplace and explores the likely lasting influence for the virus on digital transformation.
Seriously ill pediatric patient, parent, and clinician perspectives on visualizing symptom data
Authors: Vaughn Jacqueline , Kamkhoad Donruedee , Shaw Ryan J , Docherty Sharron L , Subramaniam Arvind P , Shah Nirmish
Published: February 2021

Objective

This study examined the perspectives on the use of data visualizations and identified key features seriously ill children, their parents, and clinicians prefer to see when visualizing symptom data obtained from mobile health technologies (an Apple Watch and smartphone symptom app).

Materials and Methods

Children with serious illness and their parents were enrolled into a symptom monitoring study then a subset was interviewed for this study. A study team member created symptom data visualizations using the pediatric participant’s mobile technology data. Semi-structured interviews were conducted with a convenience sample of participants (n = 14 children; n = 14 parents). In addition, a convenience sample of clinicians (n = 30) completed surveys. Pediatric and parent participants shared their preferences and perspectives on the symptom visualizations.

Results

We identified 3 themes from the pediatric and parent participant interviews: increased symptom awareness, communication, and interpretability of the symptom visualizations. Clinicians preferred pie charts and simple bar charts for their ease of interpretation and ability to be used as communication tools. Most clinicians would prefer to see symptom visualizations in the electronic health record.

Discussion

Mobile health tools offer a unique opportunity to obtain patient-generated health data. Effective, concise symptom visualizations can be used to synthesize key clinical information to inform clinical decisions and promote patient-clinician communication to enhance symptom management.

Conclusions

Effectively visualizing complex mobile health data can enhance understanding of symptom dynamics and promote patient-clinician communication, leading to tailored personalized symptom management strategies.
Components from spider venom activate macrophages against glioblastoma cells: new potential adjuvants for anticancer immunotherapy
Authors: Munhoz Jaqueline , Peron Gabriela , Bonfanti Amanda Pires , Oliveira Janine , da Rocha-e-Silva Thomaz A A , Sutti Rafael , Thomé Rodolfo , Bombeiro André Luís , Barreto Natalia , Chalbatani Ghanbar Mahmoodi , Gharagouzloo Elahe , Vitorino-Araujo João Luiz , Verinaud Liana , Rapôso Catarina
Published: February 2021

Immunomodulation has been considered an important approach in the treatment of malignant tumours. However, the modulation of innate immune cells remains an underexplored tool. Studies from our group demonstrated that the Phoneutria nigriventer spider venom (PnV) administration increased the infiltration of macrophage in glioblastoma, in addition to decreasing the tumour size in a preclinical model. The hypothesis that PnV would be modulating the innate immune system led us to the main objective of the present study: to elucidate the effects of PnV and its purified fractions on cultured macrophages. Results showed that PnV and the three fractions activated macrophages differentiated from bone marrow precursors. Further purification generated 23 subfractions named low weight (LW-1 to LW-12) and high weight (HW-1 to HW-11). LW-9 presented the best immunomodulatory effect. Treated cells were more phagocytic, migrated more, showed an activated morphological profile and induced an increased cytotoxic effect of macrophages on tumour cells. However, while M1-controls (LPS) increased IL-10, TNF-alpha and IL-6 release, PnV, fractions and subfractions did not alter any cytokine, with the exception of LW-9 that stimulated IL-10 production. These findings suggest that molecules present in LW-9 have the potential to be used as immunoadjuvants in the treatment of cancer.
Safe Together, Vulnerable Apart: How Interstitial Space in Text Logos Impacts Brand Attitudes in Tight versus Loose Cultures
Authors: Gupta Tanvi , Hagtvedt Henrik
Published: February 2021

This research demonstrates that interstitial space in textual brand logos—that is, spacious (vs. compact) arrangement of letters—unfavorably influences brand attitude by reducing product safety perceptions. When potential threats are salient, the effect tends to occur within tight (but not loose) cultures, characterized by sensitivity to threats and a need for rigid social structures. When threats are not salient, the effect appears to occur across cultures. Five studies, including lab and field experiments, as well as archival dataset analysis, provide supportive evidence.
A Dentist’s Chair: For Practicality, Comfort, or Spectacle?
Authors: Armandroff Olivia
Published: February 2021

This essay focuses on a thirteen-inch-high reclining chair with a carved walnut frame, brass base, and emerald green velvet upholstery in the Winterthur Museum collection [1 and 2]. Created by Ira Salmon of Boston circa 1866, the chair is a patent model and part of Salmon’s efforts to win a professional reputation as a dentist early in his career. This essay documents the transformation of dentistry in America from an itinerant practice in the early republic to a professionalized career in the mid-nineteenth century. It offers evidence of how the material world of dentists changed when tools of the profession became standardized and mass produced. Developing technologies facilitated reclining chairs suited for newfangled operative techniques. The essay also focuses on a period that anticipates the development of germ theory in the early twentieth century and the sterilization of the dentist’s office. In this mid-nineteenth century moment, the aesthetics of dentist offices, and their chairs’ designs, bridge a divide between the traditional values associated with dentists and those ascribed to dentists today. The patent model demonstrates Salmon’s desire to appeal to his clients’ interest by capturing the dramatic potential of a dentist’s visit while satisfying their desire for comfort and expectation of skilful technique.
Collective professional role identity in the age of artificial intelligence
Authors: Goto Masashi
Published: February 2021

The increasing use of digital technologies such as artificial intelligence (AI) may be harmful to professions and occupations. Professional role identity can be damaged as AI takes the place of people across a broad range of professional tasks. Past studies have focused on individual-level identity, yet collective-level professional role identity remains largely unstudied. In addition, identity studies have developed two separate explanations for identity shifts: one relying on professionals’ interpretation of technology and one relying on institutional logics. It is thus unclear whether and how the interpretation of technology and institutional logics coexist in a shifting identity. To address these gaps, I studied how collective-level professional role identity is being affected by AI among audit professionals in Japan. My research consisted of a textual analysis of professional publications from 2009 to 2018 and 42 interviews with Japan's national professional association and the ‘Big Four’ firm auditors. My analysis shows that a new collective professional role identity was constructed with six identity themes reflecting six interpretations of technology. These identity themes enacted a new constellation of managerial and professional logics that framed the audit profession’s future positively. This study expands our knowledge about professional role identity by showing the value of an in-depth analysis of the content of collective identity, the missing link between the interpretation of technology and institutional logics and the importance of collective identity as a guiding principle for professions. This research also helps advance hybridity literature, as well as the emerging scholarly conversation about AI and professions.
Essential role of protein kinase C βI in icariin-mediated protection against atherosclerosis
Authors: Zhang Yibing , Xu Dongsheng , Huang Peng , Zhang Yang , Li Qi , Fan Zhimin , Ren Liqun
Published: February 2021

Objectives

This study aimed to clarify the superior beneficial effects of icariin on atherosclerosis, as well as to explore the possible underlying mechanisms for its effect via the modulation of protein kinase C βI.

Methods

Lipid profiles were determined while dissected aortas were prepared of ApoE−/− mice. The expression of protein kinase C βI and phosphorylation of protein kinase C βI were determined by immunohistochemistry analysis. Human vascular smooth muscle cells were subjected to ox-LDL stimulation. MTS assay was conducted to detect cell proliferation. A transwell migration assay was performed to evaluate migration capacity. Flow cytometric analysis was used to determine cell cycle progression. Quantitative real-time PCR and western blot were performed to assess gene expression.

Results

Icariin significantly alleviated atherogenesis, as well as protein levels of protein kinase C βI and phosphorylated protein kinase C βI in the aorta. Icariin effectively suppressed cell proliferation and migration. protein kinase C βI, cyclin D1 and matrix metalloproteinase-9 were modulated in response to treatment with icariin. Protein kinase C activator reversed the protective effect of icariin on human vascular smooth muscle cells against ox- low-density lipoprotein, protein kinase C β inhibitor augmented the inhibitory effect of icariin.

Conclusions

Our findings highlight the probable application of icariin in atherosclerotic therapy and reveal that protein kinase C βI acts as a crucial regulator in the anti-atherosclerotic action of icariin.
A case series of a rare tendon rupture
Authors: Weber Sabrina , Zimmermann Bernd , Bühler Gian , Stillhard Philipp F
Published: February 2021

The distal triceps tendon rupture is a rare finding. Only 1% of tendon ruptures are related to it. The triceps brachii muscle has three parts. All of them insert together at the posterior surface of olecranon. Mostly, the tendon ruptured at this level of insertion. The typically trauma mechanism is a fall on the hand with fully extended elbow or a direct trauma. There are also some cases described after weightlifting or secondary due to insufficiency after total joint replacement of the elbow. The diagnosis is based on clinical findings. Ultrasound or magnetic resonance imaging diagnostic is secondary but might help to differentiate between partial or complete rupture as well as to assess tendon retraction. The diagnosis should be treated operatively. Until today, there is no standard of art of surgery techniques. We describe three cases with traumatic triceps tendon rupture fixed by a transosseous refixation.
SDSS-IV MaNGA: radial gradients in stellar population properties of early-type and late-type galaxies
Authors: Parikh Taniya , Thomas Daniel , Maraston Claudia , Westfall Kyle B , Andrews Brett H , Boardman Nicholas Fraser , Drory Niv , Oyarzun Grecco
Published: February 2021

We derive ages, metallicities, and individual element abundances of early- and late-type galaxies (ETGs and LTGs) out to 1.5 Re. We study a large sample of 1900 galaxies spanning 8.6–11.3 log M/M⊙ in stellar mass, through key absorption features in stacked spectra from the SDSS-IV/MaNGA survey. We use mock galaxy spectra with extended star formation histories to validate our method for LTGs and use corrections to convert the derived ages into luminosity- and mass-weighted quantities. We find flat age and negative metallicity gradients for ETGs and negative age and negative metallicity gradients for LTGs. Age gradients in LTGs steepen with increasing galaxy mass, from −0.05 ± 0.11 log Gyr/Re for the lowest mass galaxies to −0.82 ± 0.08 log Gyr/Re for the highest mass ones. This strong gradient–mass relation has a slope of −0.70 ± 0.18. Comparing local age and metallicity gradients with the velocity dispersion σ within galaxies against the global relation with σ shows that internal processes regulate metallicity in ETGs but not age, and vice versa for LTGs. We further find that metallicity gradients with respect to local σ show a much stronger dependence on galaxy mass than radial metallicity gradients. Both galaxy types display flat [C/Fe] and [Mg/Fe], and negative [Na/Fe] gradients, whereas only LTGs display gradients in [Ca/Fe] and [Ti/Fe]. ETGs have increasingly steep [Na/Fe] gradients with local σ reaching 6.50 ± 0.78 dex/log km s−1 for the highest masses. [Na/Fe] ratios are correlated with metallicity for both galaxy types across the entire mass range in our sample, providing support for metallicity-dependent supernova yields.
Deviations from tidal torque theory: Evolution of the halo spin–filament alignment
Authors: López Pablo , Cautun Marius , Paz Dante , Merchán Manuel , van de Weygaert Rien
Published: February 2021

The alignment between halo spins and the cosmic web is still poorly understood despite being a widely studied topic. Here, we study this alignment within the context of tidal torque theory (TTT) and deviations from it. To this end, we analyse the evolution of the shape and spin direction of proto-haloes, i.e. of all the volume elements associated to a z = 0 halo, with respect to the present-day filaments. We find that the major axis of proto-haloes undergoes a major change, from being strongly perpendicular to the filament spine in the initial conditions, to being preferentially aligned at the present time. In comparison, the spin orientation shows only a mild evolution: it starts slightly parallel to the filament spine, but the subsequent evolution, up to z ∼ 1, gradually changes its orientation to preferentially perpendicular. In order to analyse these signals in the TTT framework, we split the haloes according to their net spin growth with respect to the median TTT expectation, finding a clear correlation with the spin–filament alignment. At the present time, haloes whose spin grew the most are the ones most perpendicular to the filament spine, while haloes whose spin grew below the median TTT expectation are typically more aligned. The dependence of spin directions on net spin growth is already present in the initial conditions, and gets further modified by late-time, z < 2, evolution. Also, spin directions mildly deviate from the TTT predictions even at high redshift, indicating the need for extensions to the model.
A novel RNA pol II CTD interaction site on the mRNA capping enzyme is essential for its allosteric activation
Authors: Bage Marcus G , Almohammed Rajaei , Cowling Victoria H , Pisliakov Andrei V
Published: February 2021

Recruitment of the mRNA capping enzyme (CE/RNGTT) to the site of transcription is essential for the formation of the 5′ mRNA cap, which in turn ensures efficient transcription, splicing, polyadenylation, nuclear export and translation of mRNA in eukaryotic cells. The CE GTase is recruited and activated by the Serine-5 phosphorylated carboxyl-terminal domain (CTD) of RNA polymerase II. Through the use of molecular dynamics simulations and enhanced sampling techniques, we provide a systematic and detailed characterization of the human CE–CTD interface, describing the effect of the CTD phosphorylation state, length and orientation on this interaction. Our computational analyses identify novel CTD interaction sites on the human CE GTase surface and quantify their relative contributions to CTD binding. We also identify, for the first time, allosteric connections between the CE GTase active site and the CTD binding sites, allowing us to propose a mechanism for allosteric activation. Through binding and activity assays we validate the novel CTD binding sites and show that the CDS2 site is essential for CE GTase activity stimulation. Comparison of the novel sites with cocrystal structures of the CE–CTD complex in different eukaryotic taxa reveals that this interface is considerably more conserved than previous structures have indicated.
Phase I dose-escalation, safety, and CNS pharmacokinetic study of dexanabinol in patients with brain cancer
Authors: Juarez Tiffany M , Piccioni David , Rose Lara , Nguyen Angel , Brown Bradley , Kesari Santosh
Published: February 2021

Background

Dexanabinol is a synthetic analogue of tetrahydrocannabinol identified as a potential anti-cancer therapeutic by e-Therapeutics PLC. Dexanabinol was selected for further investigation based on its preclinical tumoricidal activity. This phase I dose-escalation trial examined the safety, drug penetration into the central nervous system (CNS), preliminary antitumor activity, and recommended phase II dose.

Methods

Dexanabinol formulated in cremophor/ethanol was administered once weekly via 3-hour intravenous infusion to patients with brain cancer.

Results

A total of 26 patients were dosed once weekly at 2, 4, 8, 16, 24, 28, and 36 mg/kg. Two patients at 36 mg/kg were nonevaluable for dose level confirmation, having withdrawn early for reasons unrelated to study treatment. A recommended phase II dose of dexanabinol was established at 28 mg/kg due to related, reversible adverse events at higher dose levels that required medications for symptomatic relief. The most common drug-related toxicities were the depressed level of consciousness and lightheadedness, diarrhea, itching, fatigue, chest discomfort, and tingling in the mouth. Systemic exposure to dexanabinol (AUC0-t and Cmax) increased from 2 to 36 mg/kg, with dose nonproportionality apparent at the highest dose; dexanabinol was present in appreciable levels in the cerebrospinal fluid (CSF), which implies the possibility of exposure of intracranial tumors to drug. Five of 24 efficacy-evaluable patients (21%) experienced stable disease with a median duration of 2 cycles (28-day cycle) as the best response.

Conclusions

Dexanabinol administered weekly by intravenous infusion was safe and well-tolerated up to 28 mg/kg in brain cancer patients, but has limited antitumor activity in patients with brain cancer.