bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of transcranial direct current stimulation on post-stroke fatigue
Authors: De Doncker William , Ondobaka Sasha , Kuppuswamy Annapoorna
Published: November 2020

Background

Fatigue is one of the most commonly reported symptoms post-stroke, which has a severe impact on quality of life. Post-stroke fatigue is associated with reduced motor cortical excitability, specifically of the affected hemisphere.

Objective

The aim of this exploratory study was to assess whether fatigue symptoms can be reduced by increasing cortical excitability using anodal transcranial direct current stimulation (tDCS).

Methods

In this sham-controlled, double-blind intervention study, tDCS was applied bilaterally over the primary motor cortex in a single session in thirty stroke survivors with high severity of fatigue. A questionnaire-based measure of trait fatigue (primary outcome) was obtained before, after a week and a month post stimulation. Secondary outcome measures of state fatigue, motor cortex neurophysiology and perceived effort were also assessed pre, immediately post, a week and a month post stimulation.

Results

Anodal tDCS significantly improved fatigue symptoms a week after real stimulation when compared to sham stimulation. There was also a significant change in motor cortex neurophysiology of the affected hemisphere and perceived effort, a week after stimulation. The degree of improvement in fatigue was associated with baseline anxiety levels.

Conclusion

A single session of anodal tDCS improves fatigue symptoms with the effect lasting up to a week post stimulation. tDCS may therefore be a useful tool for managing fatigue symptoms post-stroke.
Remdesivir induced viral RNA and subgenomic RNA suppression, and evolution of viral variants in SARS-CoV-2 infected patients
Authors: Boshier Florencia A.T. , Pang Juanita , Penner Justin , Hughes Joseph , Parker Matthew , Shepherd James , Alders Nele , Bamford Alasdair , Grandjean Louis , Grunewald Stephanie , Hatcher James , Best Timothy , Dalton Caroline , Bynoe Patricia Dyal , Frauenfelder Claire , Köeglmeier Jutta , Myerson Phoebe , Roy Sunando , Williams Rachel ,   The COVID-19 Genomics UK (COG-UK) consortium, Thomson Emma C , de Silva Thushan I , Goldstein Richard A. , Breuer Judith
Published: November 2020

While changes in SARS-CoV-2 viral load over time have been documented, detailed information on the impact of remdesivir and how it might alter intra-host viral evolution is limited. Sequential viral loads and deep sequencing of SARS-CoV-2 recovered from the upper respiratory tract of hospitalised children revealed that remdesivir treatment suppressed viral RNA levels in one patient but not in a second infected with an identical strain. Evidence of drug resistance to explain this difference was not found. Reduced levels of subgenomic (sg) RNA during treatment of the second patient, suggest an additional effect of remdesivir on viral replication that is independent of viral RNA levels. Haplotype reconstruction uncovered persistent SARS-CoV-2 variant genotypes in four patients. We conclude that these are likely to have arisen from within-host evolution, and not co-transmission, although superinfection cannot be excluded in one case. Sample-to-sample heterogeneity in the abundances of variant genotypes is best explained by the presence of discrete viral populations in the lung with incomplete population sampling in diagnostic swabs. Such compartmentalisation is well described in serious lung infections caused by influenza and Mycobacterium tuberculosis and has been associated with poor drug penetration, suboptimal treatment and drug resistance. Our data provide evidence that remdesivir is able to suppress SARS-CoV-2 replication in vivo but that its efficacy may be compromised by factors reducing penetration into the lung. Based on data from influenza and Mycobacterium tuberculosis lung infections we conclude that early use of remdesivir combined with other agents should now be evaluated.

Summary Sentence

Deep sequencing of longitudinal samples from SARS-CoV-2 infected paediatric patients identifies evidence of remdesivir-associated inhibition of viral replication in vivo and uncovers evidence of within host evolution of distinct viral genotypes.
Causal effects of circulating cytokine concentrations on risk of Alzheimer’s disease: A bidirectional two-sample Mendelian randomization study
Authors: Pagoni Panagiota , Howe Laura D , Smith George Davey , Ben-Shlomo Yoav , Stergiakouli Evie , Anderson Emma L
Published: November 2020

Background

There is considerable interest in the role of neuroinflammation in the pathogenesis of Alzheimer’s disease. Evidence from observational studies suggests an association between cytokine concentrations and Alzheimer’s disease. However, establishing a causal role of cytokine concentrations on risk of Alzheimer’s disease is challenging due to bias from reverse causation and residual confounding.

Methods

We used two-sample MR to explore causal effects of circulating cytokine concentrations on Alzheimer’s disease and vice versa, employing genetic variants associated with cytokine concentrations (N=8,293) and Alzheimer’s disease (71,880 cases / 383,378 controls) from the largest non-overlapping genome-wide association studies (GWAS) of European ancestry.

Results

There was weak evidence to suggest that 1 standard deviation (SD) increase in levels of CTACK (CCL27) (OR= 1.09 95%CI: 1.01 to 1.19, p=0.03) increased risk of Alzheimer’s disease. There was also weak evidence of a causal effect of 1 SD increase in levels of MIP-1b (CCL4) (OR=1.04 95%CI: 0.99 to 1.09, p=0.08), Eotaxin (OR=1.08 95%CI: 0.99 to 1.17, p =0.10), GROa (CXCL1) (OR=1.04 95%CI: 0.99 to 1.10, p=0.15), MIG (CXCL9) (OR=1.17 95%CI: 0.97 to 1.41, p=0.10), IL-8 (Wald Ratio: OR=1.21 95%CI: 0.97 to 1.51, p=0.09) and IL-2 (Wald Ratio: OR=1.21 95%CI: 0.94 to 1.56, p=0.14) on greater risk of Alzheimer’s disease. There was little evidence of a causal effect of genetic liability to Alzheimer’s disease on circulating cytokine concentrations.

Conclusions

Our study provides some evidence supporting a causal role of cytokines in the pathogenesis of Alzheimer’s disease. However, more studies are needed to elucidate the specific mechanistic pathways via which cytokines alter the risk of Alzheimer’s disease.
Lipidomics and Dietary Assessment of Infant Formulas Reveal High Intakes of Major Cholesterol Oxidative Product (7-ketocholesterol)
Authors: Kilvington Alice , Barnaba Carlo , Rajasekaran Surender , Leimanis Mara L. , Medina-Meza Ilce Gabriela
Published: November 2020

Approximately two-thirds of US infants receive infant formula (IF) as a primary or sole nutritional source during the first six months of life. IF is available in a variety of commercial presentations, although from a manufacturing standpoint, they can be categorized in powder-(PIF) or liquid-(LIF) based formulations. Herein, thirty commercial IFs were analyzed in their oxidative and non-oxidative lipidomics profiles. Results show that LIFs have a characteristic lipidomic fingerprint, enriched in an oxidated form of cholesterol, and a lower load of phytosterols. We identified 7-ketocholesterol – a major end-product of cholesterol oxidation – as a potential biomarker of IF manufacturing. Our data allowed re-classification of IF based on their metabolomic fingerprint, resulting in three groups assigned with low-to-high oxidative status. Finally, we modeled the dietary intake for cholesterol, sterols, and 7-ketocholesterol in the first year of life. The database provided in this study will be instrumental for scientists interested in infant nutrition, to establish bases for epidemiological studies aimed to find connections between nutrition and diet-associated diseases, such as sitosterolemia.
Investigating Blunt Force Trauma to the Larynx: The Role of Inferior-Superior Vocal Fold Displacement on Phonation
Authors: Stewart Molly E. , Erath Byron D.
Published: November 2020

Blunt force trauma to the larynx, which may result from motor vehicle collisions, sports activities, etc., can cause significant damage, often leading to displaced fractures of the laryngeal cartilages, thereby disrupting vocal function. Current surgical interventions primarily focus on airway restoration to stabilize the patient, with restoration of vocal function usually being a secondary consideration. Due to laryngeal fracture, asymmetric vertical misalignment of the left or right vocal fold (VF) in the inferior-superior direction often occurs. This affects VF closure and can lead to a weak, breathy voice requiring increased vocal effort. It is unclear, however, how much vertical VF misalignment can be tolerated before voice quality degrades significantly. To address this need, the influence of inferior-superior VF displacement on phonation is investigated in 1.0 mm increments using synthetic, self-oscillating VF models in a physiologically-representative facility. Acoustic (SPL, frequency, H1-H2, jitter, and shimmer), kinematic (amplitude and phase differences), and aerodynamic parameters (flow rate and subglottal pressure) are investigated as a function of inferior-superior vertical displacement. Significant findings include that once the inferior-superior medial length of the VF is surpassed, sustained phonation degrades significantly, becoming severely pathological. If laryngeal reconstruction approaches can ensure VF contact is maintained during phonation (i.e., vertical displacement doesn’t surpass VF medial length), better vocal outcomes are expected.
Chemoproteomics Maps Glycolytic Targetome in Cancer Cells
Authors: Tian Yang , Wan Ning , Ding Ming , Shao Chang , Wang Nian , Bao Qiuyu , Lu Wenjie , Hu Haiyang , Sun Huiyong , Yang Chenxi , Zhou Kun , Chen Shuai , Wang Guangji , Ye Hui , Hao Haiping
Published: November 2020

Hyperactivated glycolysis, favoring uncontrolled growth and metastasis by producing essential metabolic intermediates engaging bioenergetics and biosynthesis, is a metabolic hallmark of most cancer cells. Although sporadic information has revealed glycolytic metabolites also possess non-metabolic function as signaling molecules, it remains largely elusive how these metabolites interact with and functionally regulate their binding targets. Here we introduce a Target Responsive Accessibility Profiling (TRAP) approach that measures ligand binding-induced steric hindrance in protein targets via global profiling accessibility changes in reactive lysines, and mapped 913 target candidates and 2,487 interactions for 10 major glycolytic metabolites in cancer cells via TRAP. The elucidated targetome uncovers diverse regulatory modalities of glycolytic metabolites involving the direct perturbation of carbohydrate metabolism enzymes, intervention of transcriptional control, modulation of proteome-level acetylation and protein complex assemblies. The advantages gained from glycolysis by cancer cells are expanded by discovering lactate as a ligand for an orphan transcriptional regulator TRIM 28 that promotes p53 degradation, and by identifying pyruvate acting against a cell apoptosis inducer trichostatin A via attenuating protein acetylation. Lastly, the inhibition of glycolytic key enzymes led to identify an intrinsically active glycolytic intermediate glyceraldehyde 3-phosphate that elicits its cytotoxicity by engaging with ENO1 and MTHFD1. Collectively, the glycolytic targetome depicted by TRAP constitutes a fertile resource for understanding how glycolysis finely tunes metabolism and signaling in support of cancer cells, and fostering the exploitation of glycolytic targetome as promising nodes for anti-cancer therapeutics development.
Detecting SARS-CoV-2 variants with SNP genotyping
Authors: Harper Helen , Burridge Amanda J. , Winfield Mark , Finn Adam , Davidson Andrew D. , Matthews David , Hutchings Stephanie , Vipond Barry , Jain Nisha , Edwards Keith J ,   The COVID-19 Genomics UK (COG-UK) consortium, Barker Gary
Published: November 2020

Tracking genetic variations from positive SARS-CoV-2 samples yields crucial information about the number of variants circulating in an outbreak and the possible lines of transmission but sequencing every positive SARS-CoV-2 sample would be prohibitively costly for population-scale test and trace operations. Genotyping is a rapid, high-throughput and low-cost alternative for screening positive SARS-CoV-2 samples in many settings. We have designed a SNP identification pipeline to identify genetic variation using sequenced SARS-CoV-2 samples. Our pipeline identifies a minimal marker panel that can define distinct genotypes. To evaluate the system we developed a genotyping panel to detect variants-identified from SARS-CoV-2 sequences surveyed between March and May 2020- and tested this on 50 stored qRT-PCR positive SARS-CoV-2 clinical samples that had been collected across the South West of the UK in April 2020. The 50 samples split into 15 distinct genotypes and there was a 76% probability that any two randomly chosen samples from our set of 50 would have a distinct genotype. In a high throughput laboratory, qRT-PCR positive samples pooled into 384-well plates could be screened with our marker panel at a cost of < £1.50 per sample. Our results demonstrate the usefulness of a SNP genotyping panel to provide a rapid, cost-effective, and reliable way to monitor SARS-CoV-2 variants circulating in an outbreak. Our analysis pipeline is publicly available and will allow for marker panels to be updated periodically as viral genotypes arise or disappear from circulation.
SARS-CoV-2 infection suppresses ACE2 function and antiviral immune response in the upper respiratory tract of infected patients
Authors: Gutiérrez-Chamorro Lucía , Riveira-Muñoz Eva , Barrios Clara , Palau Vanesa , Massanella Marta , Garcia-Vidal Edurne , Badia Roger , Pedreño Sònia , Senserrich Jordi , Rodríguez Eva , Clotet Bonaventura , Cabrera Cecilia , Mitjà Oriol , Crespo Marta , Pascual Julio , Riera Marta , Ballana Ester
Published: November 2020

There is an urgent need to elucidate the molecular mechanisms underlying the transmissibility and pathogenesis of SARS-CoV-2. ACE2 is a host ectopeptidase with well-described anti-inflammatory and tissue protective functions and the receptor for the virus. Understanding SARS-CoV-2-ACE2 interaction and the expression of antiviral host genes in early infection phase is crucial for fighting the pandemic. We tested the significance of soluble ACE2 enzymatic activity longitudinally in positive nasopharyngeal swabs at two time points after symptom consultation, along with gene expression profiles ofACE2, its proteases,ADAM17andTMPRRS2, and interferon-stimulated genes (ISGs),DDX58,CXCL10andIL-6. Soluble ACE2 activity decreased during infection course, in parallel toACE2gene expression. On the contrary, SARS-CoV-2 infection induced expression of the ISG genes in positive SARS-CoV-2 samples at baseline compared to negative control subjects, although this increase wanes with time. These changes positively correlated with viral load. Our results demonstrate the existence of mechanisms by which SARS-CoV-2 suppressACE2expression and function casting doubt on the IFN-induced upregulation of the receptor. Moreover, we show that initial intracellular viral sensing and subsequent ISG induction is also rapidly downregulated. Overall, our results offer new insights into ACE2 dynamics and inflammatory response in the human upper respiratory tract that may contribute to understand the early antiviral host response to SARS-CoV-2 infection.
Heme dependent transcriptional regulation of thePseudomonas aeruginosatandem sRNAprrF1,F2locus by the cytoplasmic heme binding protein PhuS
Authors: Wilson Tyree , Mouriño Susana , Wilks Angela
Published: November 2020

Pseudomonas aeruginosais an opportunistic pathogen requiring iron for its survival and virulence.P. aeruginosacan acquire iron from heme via the heme assimilation system (Has) andPseudomonasheme uptake (Phu) systems. The Has and Phu systems have non-redundant roles in heme sensing and transport, respectively. However, despite their respective roles heme taken up by either the Has or Phu system is regulated at the metabolic level by the cytoplasmic heme binding protein PhuS, which controls heme flux through the iron-regulated heme oxygenase HemO. Herein, through a combination of CHIP-PCR, EMSA and fluorescence anisotropy we show PhuS binds upstream of the tandem iron-responsive sRNAsprrF1,F2.Furthermore, qPCR analysis of the PAO1 WT and ΔphuSallelic strain shows loss of PhuS abrogates the heme dependent regulation of PrrH. Taken together our data shows PhuS, in addition to its role in regulating extracellular heme metabolism also functions as a transcriptional regulator of the heme-dependent sRNA, PrrH. This dual function of PhuS is central to integrating extracellular heme utilization into the PrrF/PrrH sRNA regulatory network critical forP. aeruginosaadaptation and virulence within the host.
Mortality rates in matched cohort, pseudo-randomised and randomised trials of convalescent plasma given to COVID-19 patients
Authors: Ahmad Amar , Salsabil Marwa , Oliver Tim
Published: November 2020

Introduction

For more than 80 years convalescent or immune sera has been used in severe life threatening infections. Since March of this year a rapidly increasing number of publications have reported series of Convalescent plasma (CP) investigations in severely ill COVID-19 patients.

Objective

a brief CP scoping review focusing on early mortality

Methods

We searched available data bases. Three randomised trials, two pseudo-randomised observations and twelve matched cohort studies were identified. Random-effects meta-analyses were performed on extracted data

Results

A total of 2,378 CP treated and 5188 “controls” in 17 studies. Individually only two studies were significant for reduction of deaths to 30 days, but all showed a similar percentage reduction. When pooled, meta-analysis was undertaken. It showed that the overall reduction of death was significant for all series RR 0.710 (p=0.00001), all matched cohort series RR = 0.610 (p-value = 0.001) and the two pseudo-randomised series RR 0.747 (p=0.005) but not the three technically inadequate randomised trials, RR 0.825 (p=0.397). In two of these randomised trials, there was faster clearance of Viral DNA at 72 hours after CP than placebo

Conclusion

It is hoped the significance of this less than perfect data will increase interest in completing the delayed randomised trials as the results suggest they could be better than currently licenced drugs. Given increasing published evidence of increased risk of both diagnosis and death from COVID-19 in patients with severe Vitamin-D deficiency, future studies should also study influence of Vitamin-D status of donor and recipient on outcome.
COVID-19: how the pandemic impacted the emergency department and urgent surgical activity in a medium-size Italian hospital
Authors: Pinotti Enrico , Carissimi Francesca , Baronio Gianluca , Montuori Mauro , Ongaro Deborah , Vasino Michele Ciocca
Published: November 2020

Backgrounds

COVID-19 has grown rapidly in Lombardy, particularly in the province of Bergamo. To deal with the pressure the pandemic has exerted on the Italian health system; many hospitals have had to reorganize their medical and surgical activities. The aim of this study was to evaluate how the pandemic influenced the emergency department and urgent surgical activity in a medium-size hospital in the province of Bergamo.

Methods

In this retrospective observational study, we analyzed the number of admissions to the medical and surgical Emergency Room and their severity compared with those in the same period in previous years (2011-2019). Admission in the medical and surgical department and urgent surgical operation was also assessed.

Results

From March 7th to April 5th, 2020, we observe a reduction in emergency department access (−53%) when compared with the corresponding period of previous years. The number of medical admissions was similar to the past years (+0.9%), we observed a drastic reduction of surgical patients (−82.5%). We experienced a significant increase in hospitalizations in the medical department (+359%) and a reduction of admission in the surgical department (−71.2%).

Conclusion

SARS-CoV2 disease has spread so suddenly and severely that it has stressed Italian health system, in particular the Lombard one. Our data show the rise of critical medical ER accesses and the significant expansion in hospitalisation in the medical department with the necessary hospital reorganisation to face COVID-19 emergency. We also observed a reduction in both surgical ER accesses and urgent surgical activity.
Unmasking Seasonal Cycles in Human Fertility: How holiday sex and fertility cycles shape birth seasonality
Authors: Symul L. , Hsieh P. , Shea A. , Moreno CRC. , Skene D.J. , Holmes S. , Martinez M
Published: November 2020

The mechanisms of human birth seasonality have been debated for over 150 years1. In particular, the question of whether sexual activity or fertility variations drive birth seasonality has remained open and challenging to test without large-scale data on sexual activity2,3. Analyzing data from half-a-million users worldwide collected from the female health tracking app Clue combined with birth records, we inferred that birth seasonality is primarily driven by seasonal fertility, yet increased sexual activity around holidays explains minor peaks in the birth curve. Our data came from locations in the Northern Hemisphere (UK, US, and France) and the Southern Hemisphere (Brazil). We found that fertility peaks between the autumn equinox and winter solstice in the Northern Hemisphere locations and shortly following the winter solstice in the Southern Hemisphere locations.
Aberrant gliogenesis and excitation in MEF2C autism patient hiPSC-neurons and cerebral organoids
Authors: Trudler Dorit , Ghatak Swagata , Parker James , Talantova Maria , Grabauskas Titas , Noveral Sarah Moore , Teranaka Mayu , Luevanos Melissa , Dolatabadi Nima , Bakker Clare , Lopez Kevin , Sultan Abdullah , Chan Agnes , Choi Yongwook , Kawaguchi Riki , Schork Nicholas , Stankiewicz Pawel , Garcia-Bassets Ivan , Kozbial Piotr , Rosenfeld Michael G. , Nakanishi Nobuki , Geschwind Daniel H. , Chan Shing Fai , Ambasudhan Rajesh , Lipton Stuart A.
Published: November 2020

MEF2C has been shown to be a critical transcription factor for neurodevelopment, whose loss-of-function mutation in humans results in MEF2C haploinsufficiency syndrome (MHS), a severe form of autism spectrum disorder (ASD)/intellectual disability (ID). Here, we use patient hiPSC-derived cerebrocortical neurons and cerebral organoids to characterize MHS deficits. Unexpectedly, we found an aberrant micro-RNA-mediated gliogenesis pathway that contributes to decreased neurogenesis. We also demonstrate network-level hyperexcitability in neurons, as evidenced by excessive synaptic and extrasynaptic activity contributing to excitatory/inhibitory (E/I) imbalance. Notably, the extrasynaptic NMDA receptor antagonist, NitroSynapsin, corrects this aberrant electrical activity associated with abnormal phenotypes. During neurodevelopment, MEF2C regulates many ASD-associated gene networks suggesting that our approach may lead to personalized therapy for multiple forms of ASD.

One sentence summary

Autism-like MEF2C+/-patient hiPSC models show miRNA-mediated overproduction of astrocytes and hyperactivity of neurons.
Ngn2 induces diverse neuronal lineages from human pluripotency
Authors: Lin Hsiu-Chuan , He Zhisong , Ebert Sebastian , Schörnig Maria , Santel Malgorzata , Weigert Anne , Hevers Wulf , Kasri Nael Nadif , Taverna Elena , Camp J. Gray , Treutlein Barbara
Published: November 2020

Human neurons engineered from induced pluripotent stem cells (iPSCs) through Neurogenin 2 (Ngn2) overexpression are widely used to study neuronal differentiation mechanisms and to model neurological diseases. However, the differentiation paths and heterogeneity of emerged neurons have not been fully explored. Here we used single-cell transcriptomics to dissect the cell states that emerge during Ngn2 overexpression across a time course from pluripotency to neuron functional maturation. We find a substantial molecular heterogeneity in the neuron types generated, with at least two populations that express genes associated with neurons of the peripheral nervous system. Neuron heterogeneity is observed across multiple iPSC clones and lines from different individuals. We find that neuron fate acquisition is sensitive to Ngn2 expression level and the duration of Ngn2 forced expression. Our data reveals that Ngn2 dosage can regulate neuron fate acquisition, and that Ngn2-iN heterogeneity can confound results that are sensitive to neuron type.
Abrupt light transitions in illuminance and CCT result in different temporal dynamics and interindividual variability for sensation, comfort and alertness
Authors: Kompier M.E. , Smolders K.C.H.J. , de Kort Y.A.W.
Published: November 2020

Detailed insights in both visual effects of light and effects beyond vision due to manipulations in illuminance and correlated color temperature (CCT) are needed to optimize study protocols as well as to design light scenarios for practical applications. This study investigated temporal dynamics and interindividual variability in subjective evaluations of sensation, comfort and mood as well as subjective and objective measures of alertness, arousal and thermoregulation following abrupt transitions in illuminance and CCT in a mild cold environment. The effects could be uniquely attributed to changes in illuminance or CCT and no interaction effects of illuminance and CCT were found for any of these markers. Responses to the abrupt transitions in illuminance and CCT always occurred immediately and exclusively amongst the subjective measures. Most of these responses diminished over time within the 45-minute light manipulation. In this period, no responses were found for objective measures of vigilance, arousal nor thermoregulation. Significant interindividual variability occurred only in the visual comfort evaluation in response to changes in the intensity of the light. The results indicate that the design of dynamic light scenarios aimed to enhance human alertness and vitality requires tailoring to the individual to create visually comfortable environments.
Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape
Authors: McCarthy Kevin R. , Rennick Linda J. , Nambulli Sham , Robinson-McCarthy Lindsey R. , Bain William G. , Haidar Ghady , Duprex W. Paul
Published: November 2020

Zoonotic pandemics, like that caused by SARS-CoV-2, can follow the spillover of animal viruses into highly susceptible human populations. Their descendants have adapted to the human host and evolved to evade immune pressure. Coronaviruses acquire substitutions more slowly than other RNA viruses, due to a proofreading polymerase. In the spike glycoprotein, we find recurrent deletions overcome this slow substitution rate. Deletion variants arise in diverse genetic and geographic backgrounds, transmit efficiently, and are present in novel lineages, including those of current global concern. They frequently occupy recurrent deletion regions (RDRs), which map to defined antibody epitopes. Deletions in RDRs confer resistance to neutralizing antibodies. By altering stretches of amino acids, deletions appear to accelerate SARS-CoV-2 antigenic evolution and may, more generally, drive adaptive evolution.
The human hippocampus plays a time-limited role in retrieving autobiographical memories
Authors: Gilmore Adrian W. , Quach Alina , Kalinowski Sarah E. , Gonzalez-Araya Estefanía I. , Gotts Stephen J. , Schacter Daniel L. , Martin Alex
Published: November 2020

The necessity of the human hippocampus for remote autobiographical recall remains fiercely debated. The standard model of consolidation predicts a time-limited role for the hippocampus, but the competing multiple trace/trace transformation theories posit indefinite involvement. Lesion evidence remains inconclusive, and the inferences one can draw from fMRI have been limited by reliance on covert (silent) recall, which obscures dynamic, moment-to-moment content of retrieved memories. Here, we capitalized on advances in fMRI denoising to employ overtly spoken recall. Forty participants retrieved recent and remote memories, describing each for approximately two minutes. Details associated with each memory were identified and modeled in the fMRI timeseries data using a variant of the Autobiographical Interview procedure, and activity associated with the recall of recent and remote memories was then compared. Posterior hippocampal regions exhibited temporally-graded activity patterns (recent events > remote events), as did several regions of frontal and parietal cortex. Consistent with predictions of the standard model, recall-related hippocampal activity differed from a non-autobiographical control task only for recent, and not remote, events. Task-based connectivity between posterior hippocampal regions and others associated with mental scene construction also exhibited a temporal gradient, with greater connectivity accompanying the recall of recent events. These findings support predictions of the standard model of consolidation and demonstrate the potential benefits of overt recall in neuroimaging experiments.
Crystal structure of a new hydrate form of the NSAID sodium diclofenac
Authors: Angel Nieto Ismael , Bernès Sylvain , Pérez-Benítez Aarón
Published: November 2020

The crystal structure is reported of sodium 2-[2-(2,6-dichloroanilino)phenyl]acetate 3.5-hydrate or tetra-μ-aqua-κ8
O:O-decaaquabis{μ3-2-[2-(2,6-dichloroanilino)phenyl]acetato-κ3
O:O:O}tetrasodium(I) bis{2-[2-(2,6-dichloroanilino)phenyl]acetate}, {[Na4(C14H10Cl2NO2)2(H2O)14](C14H10Cl2NO2)2}
n
, which represents a new hydrate form of the NSAID sodium diclofenac (SD). The triclinic unit cell contains one ionic compound with formula Na4(C14H10Cl2NO2)4(H2O)14, in which two symmetry-related carboxylate anions C14H10Cl2NO2
− are bonded to a centrosymmetric [Na4]4+ core cationic cluster, while the others are only hydrogen bonded to the cationic cluster. The conformation for the anions is similar to that found in other diclofenac compounds, and the [Na4(Ocarbox)2(H2O)14]4+ cluster displays an unprecedented geometry, which can be described as an incomplete dicubane cluster formed by face-sharing incomplete cubes. A complex framework of O—H...O hydrogen bonds stabilizes the crystal structure. The herein reported crystal structure for SD·3.5H2O in space group P\overline{1} is different from those previously reported for other hydrates, namely SD·4.75H2O (P21) and SD·5H2O (P21/m).
Numerical investigation of the effect of the injection angle on the spray structures of an air-blast atomizer
Authors: Chen Sheng , Xing Yuming , Liu Xin , Zhao Liang
Published: November 2020

Purpose

The purpose of this study is to investigate the effect of the injection angle α on the spray structures of an air-blast atomizer and help enhance the understanding of droplet-gas mixing process in such atomizers in the engineering domain.

Design/methodology/approach

The phenomena in the air-blast atomizer were numerically modelled using the computational fluid dynamics software Fluent 17.2. The Euler-Lagrange approach was applied to model the droplet tracking and droplet-gas interaction in studied cases. The standard k-ε model was used to simulate the turbulent flow. A model with a modified drag coefficient was used to consider the effects of the bending of the liquid column and its penetration in the primary breakup region. The Kelvin-Helmholtz, Rayleigh-Taylor model was applied to consider the secondary breakup of the droplets.

Findings

The basic spatial distribution and spray structures of the droplets corresponding to the angled liquid jet (α = 60°) were similar to those reported in liquid jets injected transversely into a gaseous crossflow studies. The injection angle α did not considerably influence the averaged Sauter to mean diameter (SMD) of the cross-sections. However, the spray structures pertaining to α = 30°, α = 60° and α = 90° were considerably different. In the case of the atomizer with multiple injections, a “collision region” was observed at α = 60° and characterized by a higher ci and larger averaged SMD in the central parts of the cross-sections.

Originality/value

The injection angle α is a key design parameter for air-blast atomizers. The findings of this study can help enhance the understanding of the droplet-gas mixing process in air-blast atomizers. Engineers who design air-blast atomizers and face new challenges in the process can refer to the presented findings to obtain the desired atomization performance. The code has been validated and can be used in the engineering design process of the gas-liquid jet atomizer.
Social and health sector reform towards 2040 in Japan
Authors: Hasegawa Tomonori , Matsumoto Kunichika , Onishi Ryo , Hirata Koki
Published: November 2020

Purpose

The purpose of this paper is to examine the health sector reform toward 2040 of Japan as a super-aged society.

Design/methodology/approach

This paper discusses the current healthcare policies adopted in Japan and projects the challenges in future as a super-aged society.

Findings

Through Japanese experiences, it is considered that Community-based Integrated Care System is useful, which takes into account the perspective of health care users. Being a super-aged society, it is essential for Japan to have more consensus by further removing obstacles, and paying attention to the change of paradigm and the purpose of care.

Originality/value

Based on the case of Japan, this paper serves as a reference for other East Asian countries, which would sooner or later encounter the similar situation of becoming super-aged societies in the 21st century.
Diffuse dermal mucinosis secondary to colony‐stimulating factor 1 receptor monoclonal antibody treatment: A novel and peculiar drug‐induced diffuse cutaneous mucinosis
Authors: Olmos‐Alpiste Ferran , Segura Sonia , Tomás‐Velázquez Alejandra , Aguado Leyre , España Agustín , Arriola Edurne , Martín‐Algarra Salvador , Barranco Carlos , Lloreta Josep , Pujol Ramon M.
Published: November 2020

Colony‐stimulating factor 1 receptor (CSF1R) inhibitors represent a new class of immune‐modulatory drugs, mostly investigated in clinical trials in different malignant neoplasms. Four patients, diagnosed with recurrent or advanced malignant neoplasm and treated with a combination of anti‐programmed death ligand 1 and anti‐CSF1R monoclonal antibodies, developed an asymptomatic cutaneous eruption characterized by an ill‐defined pseudoedematous to waxy diffuse infiltration with a reticular cobblestone‐like pattern. Histopathological examination revealed diffuse mucin deposition involving the superficial and mid‐dermis with fragmented and scattered elastic fibers. The exact pathogenic mechanisms implicated in the development of mucin deposits in patients treated with CSF1R inhibitors remain to be elucidated. A reduced degradation and clearance of components of the extracellular matrix by macrophages secondary to CSF1 pathway inhibition may be hypothesized. Shredding and fragmentation of elastic fibers may be a result of the increased accumulation of mucopolysaccharides. This observation illustrates the new spectrum of skin‐related toxicities secondary to new targeting therapies. This may contribute to a better understanding of the underlying pathogenic mechanisms in skin diseases characterized by a persistent dermal glycosaminoglycan deposition.
Functional group changes and chemical bond‐dependent dielectric properties of lotus seed flour with microwave vacuum drying
Authors: Wang Weiwei , Zheng Baodong , Tian Yuting
Published: November 2020

Microwave vacuum drying (MVD) was applied to dehydrate lotus (Nelumbo nuciferaGaertn.) seeds. This paper evaluated the changes of molecular, crystalline, and morphological structural properties of lotus seeds after MVD. The results showed the frequency of δ(CH) bending, β(CH), ν(OH), and carbon–oxygen double bonds (C = O) increased with increasing microwave power density. Moreover, as microwave power density increased, the transition enthalpy of crystallinity gradually increased, which was related to the formation of crystalline starch, re‐crystallization, and complexes of starch–lipid structure depending on the hydrogen bonds formed. The MVD process resulted molecular polarity of lotus seeds, whereas the dielectric properties also changed. The dielectric properties interacted with the changes of molecules and crystalline structure. The morphology of lotus seed flour changed because the shape of starch granules was disrupted and the granules became aggregated with nonstarch components as the microwave power density increased. All these results explain the interactions among polymer molecules in lotus seeds dried by MVD.
Distinguishing between long‐term‐stored and fresh chili pepper powder through fingerprinting of volatiles by headspace capillary‐gas chromatography‐ion mobility spectrometry
Authors: Hwang In Min , Park Boyeon , Yang Ji‐Su , Ha Ji‐Hyoung
Published: November 2020

Long‐term storage of chili pepper powder results in physicochemical and microbiological changes that decrease its commercial value; these changes occur owing to fungal growth and production of off‐flavor compounds. Herein, long‐term‐stored chili pepper powder (LSCPP) and fresh chili pepper powder (FCPP) were analyzed using internal transcribed spacer sequencing and volatile organic compound fingerprinting by headspace capillary‐gas chromatography‐ion mobility spectrometry. Fungal analysis detected only Xeromyces bisporus with high accuracy in all the analyzed LSCPP samples. However, the proliferation of X. bisporus on nonspecific spots complicated the distinguishing process between the two groups based solely on fungal analysis. Therefore, nine compounds (three ketones, one alcohol, two aldehydes, one ester, one furan, and one sulfur compound) obtained by autoxidation and fungal metabolism were selected as potential markers for distinguishing LSCPP and FCPP. These above‐mentioned substances, which were confirmed as off‐flavor species owing to “stale” odor, emitted lipid fragrance and were used to successfully distinguish LSCPP from FCPP using principal component analysis and linear discriminant analysis.

Practical Application

According to the research results, it was possible to discriminate between long‐term stored and fresh chili pepper powders using nine VOC markers for quality control in industry. In addition, the fungus generated from long‐term storage of chili pepper powder was Xeromyces bisporus, which was confirmed to be safe for intake because it does not form secondary toxic metabolites.
Antiquitas non fingo: Newton, the Moderns and the Science of Ancient History
Authors: Mattana Alessio
Published: November 2020

In his posthumous The Chronology of the Ancient Kingdoms Amended (1728) Isaac Newton re‐dated a number of significant events in ancient history, most importantly the Argonautic expedition and the Fall of Troy. This article explores the eighteenth‐century reception of the Chronology as a text contiguous with Newton's previous works on natural philosophy. In particular, it will be argued that the Chronology was considered as proof that the moderns had made history into a scientific discipline based on principles like those delineated in Newton's Principia.
From Classification to Recreated ‘Reality’: William Bullock's Exhibitions of Human and Natural History
Authors: Pearce Susan
Published: November 2020

In his London Museum (1809), William Bullock organised displays of his animal collections into family and contextual groups within re‐creations of their natural surroundings. Subsequently his displays of Saami material re‐created its social environment. Bullock’s exhibitions signal a significant moment in the movement from the Linnaean‐style classification of natural material by appearance to explanation of it through contextual and inherent qualities. A new kind of meaning was generated, bringing together the natural and the antiquarian in showing that the same approach transformed understanding of both. It shifted emphasis from eighteenth‐century natural philosophy towards nineteenth‐century science, both natural and human.
Eltrombopag preferentially expands haematopoietic multipotent progenitors in human aplastic anaemia
Authors: Quintino de Oliveira Bruno , Catto Luiz F. B. , Santana Bárbara A. A. , Tellechea M. Florencia , Scheucher Priscila S. , Scheinberg Phillip , Calado Rodrigo T.
Published: November 2020

Eltrombopag has been added to first‐line treatment of immune aplastic anaemia (AA), resulting in higher responses. We analysed marrow samples of AA patients who responded to immunosuppressive therapy (IST) alone or in combination with eltrombopag for the composition of the haematopoietic stem and progenitor cell (HSPC) compartment. The number of CD34+ cells and multipotent progenitors was higher in patients treated with eltrombopag (P < 0·005; P < 0·05; respectively), but not the number of stem cells. No aberrant phenotype was observed. These results indicate that eltrombopag augments CD34+ cells in vivo and preferentially expands multipotent progenitors, but not stem cells.
Stable middle‐aged face recognition: No moderation of the own‐age bias across contexts
Authors: Cronin Sophie L. , Craig Belinda M. , Lipp Ottmar V.
Published: November 2020

The own‐age bias (OAB) has been proposed to be caused by perceptual expertise and/or social‐cognitive mechanisms. Investigations into the role of social cognition have, however, yielded mixed results. One reason for this might be the tendency for research to focus on the OAB in young adults, between young and older adult faces where other‐age individuation experience is low. To explore whether social‐cognitive manipulations may be successful when observers have sufficient other‐age individuation experience, we examined biases involving middle‐aged other‐age faces and the influence of a context manipulation. Across four experiments, young adult participants were presented with middle‐aged faces alongside young or older adult faces to remember. We predicted that in contexts where middle‐aged faces were positioned as other‐age faces (alongside young adult faces), recognition performance would be worse than when they were positioned as relative own‐age faces (alongside older adult faces). However, the context manipulations did not moderate middle age face recognition. This suggests that past findings that context does not change other‐age face recognition holds for other‐age faces for which observers have higher individuation experience. These findings are consistent with a perceptual expertise account of the OAB but more investigation of the generality of these results is required.
Antitumor effects of novel mAbs against cationic amino acid transporter 1 (CAT1) on human CRC with amplified CAT1 gene
Authors: Okita Kouki , Hara Yuta , Okura Hiroshi , Hayashi Hidemi , Sasaki Yoko , Masuko Sachiko , Kitadai Eri , Masuko Kazue , Yoshimoto Soshi , Hayashi Natsumi , Sugiura Reiko , Endo Yuichi , Okazaki Shogo , Arai Sayaka , Yoshioka Toshiaki , Matsumoto Toshiharu , Makino Yasutaka , Komiyama Hiromitsu , Sakamoto Kazuhiro , Masuko Takashi
Published: November 2020

Copy number alterations detected by comparative genomic hybridization (CGH) can lead to the identification of novel cancer‐related genes. We analyzed chromosomal aberrations in a set of 100 human primary colorectal cancers (CRCs) using CGH and found a solute carrier (SLC) 7A1 gene, which encodes cationic amino acid transporter 1 (CAT1) with 14 putative transmembrane domains, in a chromosome region (13q12.3) with a high frequency of gene amplifications. SLC7A1/CAT1 is a transporter responsible for the uptake of cationic amino acids (arginine, lysine, and ornithine) essential for cellular growth. Microarray and PCR analyses have revealed that mRNA transcribed from CAT1 is overexpressed in more than 70% of human CRC samples, and RNA interference–mediated knockdown of CAT1 inhibited the cell growth of CRCs. Rats were immunized with rat hepatoma cells expressing CAT1 tagged with green fluorescent protein (GFP), and rat splenocytes were fused with mouse myeloma cells. Five rat monoclonal antibodies (mAbs) (CA1 ~ CA5) reacting with HEK293 cells expressing CAT1‐GFP in a GFP expression–dependent manner were selected from established hybridoma clones. Novel anti‐CAT1 mAbs selectively reacted with human CRC tumor tissues compared with adjacent normal tissues according to immuno‐histochemical staining and bound strongly to numerous human cancer cell lines by flow cytometry. Anti‐CAT1 mAbs exhibited internalization activity, antibody‐dependent cellular cytotoxicity, and migration inhibition activity against CRC cell lines. Furthermore, CA2 inhibited the in vivo growth of human HT29 and SW‐C4 CRC tumors in nude mice. This study suggested CAT1 to be a promising target for mAb therapy against CRCs.
Implant and prosthesis survival rates of full‐arch immediate prostheses supported by implants with and without bicortical anchorage: Up to 2 years of follow‐up retrospective study
Authors: Thomé Geninho , Caldas Waleska , Bernardes Sergio Rocha , Cartelli Carolina Accorsi , Gracher Ana Helena Pereira , Trojan Larissa Carvalho
Published: November 2020

Objectives

To compare implant and prosthesis survival rates between full‐arch immediate prostheses supported by 4 hydrophilic implants with bicortical anchorage and by 5 or 6 hydrophilic implants placed without bicortical anchorage.

Material and Methods

The sample was retrospectively selected and comprised completely edentulous patients treated with full‐arch immediate prostheses supported by Morse Taper hydrophilic implants. The selected patients were divided into four groups, according to the region of implant placement and type of anchorage. Differences in implant and prosthesis survival rates between groups, as well as the influence of bicortical anchorage on implant primary stability, were verified using Fisher's exact tests (significant at p < .05).

Results

The sample comprised 392 implants, 72 were placed in the maxilla with bicortical anchorage, and 85 were placed without. In the mandible, 140 implants were placed with and 95 were placed without bicortical anchorage. The follow‐up period was up to 24 months. A 98.8% implant survival rate was observed for the group of implants placed without bicortical anchorage in the maxilla, and of 100% for the other groups. The overall implant survival rate was 99.7% (391 of 392 implants). Prosthesis survival rate was 100% for all groups. No differences were observed between groups with respect to implant and prosthesis survival rates. Significantly higher primary stability was observed for implants placed with bicortical anchorage in both jaws.

Conclusion

Predictable results and high survival rates were achieved within the period evaluated by the present retrospective study, with immediate full‐arch prostheses when only four hydrophilic implants are placed bicortically.