bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review of Dosages of Chloroquine and Hydroxychloroquine for COVID-19 in registered Clinical Trials during First Quarter of 2020
Authors: Rana Divya RSJB , Dulal Santosh
Published: March 2020

Background

The novel corona virus disease 2019 (COVID-19) pandemic has been causing a massive global public health havoc. Use of quinolones for treatment of COVID-19 was a matter of huge discussion in scientific community. Falsified data about efficacy of the drug against COVID-19 disseminated. This review was designed to study the dosages of chloroquine and hydroxychloroquine planned to be administered in clinical trials registered up to March 2020.

Inclusion of chloroquine and hydroxychloroquine for COVID-19 treatment in Chinese national treatment guideline in the early days of the pandemic prompted numerous clinical trials in many countries to authenticate the efficacy of the drugs. Trials were designed to include chloroquine or hydroxychloroquine singly or in combination with other drugs. Almost all of the trials planned oral administration except few which used aerosol inhalation. In the later half of 2020, systematic reviews and results of those clinical trials point out the inefficacies and inadvertent adverse events due to the use of these quinolone drugs for COVID-19.

Conclusion

This study reviews the various dosages of chloroquine and hydroxychloroquine utilized in published and under-study clinical trials as assessed during the end of March 2020. Specifically, clinical trials registered in Chinese and US trial registries were examined.
Clinical features and the maternal and neonatal outcomes of pregnant women with coronavirus disease 2019
Authors: Nie Rui , Wang Shao-shuai , Yang Qiong , Fan Cui-fang , Liu Yu-ling , He Wen-cong , Jiang Mei , Liu Cheng-cheng , Zeng Wan-jiang , Wu Jian-li , Oktay Kutluk , Feng Ling , Jin Lei
Published: March 2020

BACKGROUND

There is little information about the coronavirus disease 2019 (Covid-19) during pregnancy. This study aimed to determine the clinical features and the maternal and neonatal outcomes of pregnant women with Covid-19.

METHODS

In this retrospective analysis from five hospitals, we included pregnant women with Covid-19 from January 1 to February 20, 2020. The primary composite endpoints were admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Secondary endpoints included the clinical severity of Covid-19, neonatal mortality, admission to neonatal intensive care unit (NICU), and the incidence of acute respiratory distress syndrome (ARDS) of pregnant women and newborns.

RESULTS

Thirty-three pregnant women with Covid-19 and 28 newborns were identified. One (3%) pregnant woman needed the use of mechanical ventilation. No pregnant women admitted to the ICU. There were no moralities among pregnant women or newborns. The percentages of pregnant women with mild, moderate, and severe symptoms were 13 (39.4%),19(57.6%), and 1(3%). One (3.6%) newborn developed ARDS and was admitted to the NICU. The rate of perinatal transmission of SARS-CoV-2 was 3.6%.

CONCLUSIONS

This report suggests that pregnant women are not at increased risk for severe illness or mortality with Covid-19 compared with the general population. The SARS-CoV-2 infection during pregnancy might not be associated with as adverse obstetrical and neonatal outcomes that are seen with the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infection during pregnancy. (Funded by the National Key Research and Development Program.)
Function of a novel nasal protrusion for oral-shelling within an adaptive radiation of pupfishes
Authors: St. John Michelle E. , Dixon Kristi , Martin Christopher H.
Published: March 2020

Dietary specialization on hard prey items, such as mollusks and crustaceans, is commonly observed in a diverse array of fish species. Many fish consume these types of prey by crushing the shell to consume the soft tissue within, but a few fishes extricate the soft tissue without breaking the shell using a method known as oral shelling. Oral shelling involves pulling a mollusk from its shell and may be a way to subvert an otherwise insurmountable shell defense. However, the biomechanical requirements and potential adaptations for oral shelling are unknown. Here, we test the hypothesis that a novel nasal protrusion is an adaptation for oral shelling in a durophagous pupfish (Cyprinodon brontotheroides). We first demonstrate oral shelling in this species and then predicted that a larger nasal protrusion would allow pupfish to consume larger snails. Durophagous pupfish are found within an endemic radiation of pupfish on San Salvador Island, Bahamas. We took advantage of closely related sympatric species and outgroups to test: 1) whether durophagous pupfish shell and consume more snails than other species, 2) if F1 and F2 durophagous hybrids consume similar amounts of snails as purebred durophagous pupfish, and 3) to determine if nasal protrusion size in parental and hybrid populations increases the maximum diameter snail consumed. We found that durophagous pupfish and their hybrids consumed the most snails, but did not find a strong association between nasal protrusion size and maximum snail size consumed within the parental or F2 hybrid population, suggesting that the size of their novel nasal protrusion does not provide a major benefit in oral shelling. Instead, we suggest that nasal protrusion may increase feeding efficiency, act as a sensory organ, or is a sexually selected trait, and that a strong feeding preference may be most important for oral shelling.

Significance Statement

Specialization on hard-shell prey items (i.e. durophagy) is a common dietary niche among fishes. Oral shelling is a rare technique used by some durophagous fish to consume prey items like snails; however, adaptations for oral shelling are still unknown. Here, we document the first evidence of oral shelling in a cyprinodontiform fish, the durophagous pupfish (Cyprinodon brontotheroides), and experimentally test whether its novel nasal protrusion is an adaptation for oral shelling using hybrid feeding trials.
Immune Cell Profiling of COVID-19 Patients in the Recovery Stage by Single-Cell Sequencing
Authors: Wen Wen , Su Wenru , Tang Hao , Le Wenqing , Zhang Xiaopeng , Zheng Yingfeng , Liu Xiuxing , Xie Lihui , Li Jianmin , Ye Jinguo , Cui Xiuliang , Miao Yushan , Wang Depeng , Dong Jiantao , Xiao Chuanle , Chen Wei , Wang Hongyang
Published: March 2020

COVID-19, caused by SARS-CoV-2, has recently affected over 300,000 people and killed more than 10,000. The manner in which the key immune cell subsets change and their states during the course of COVID-19 remain unclear. Here, we applied single-cell technology to comprehensively characterize transcriptional changes in peripheral blood mononuclear cells during the recovery stage of COVID-19. Compared with healthy controls, in patients in the early recovery stage (ERS) of COVID-19, T cells decreased remarkably, whereas monocytes increased. A detailed analysis of the monocytes revealed that there was an increased ratio of classical CD14++ monocytes with high inflammatory gene expression as well as a greater abundance of CD14++IL1B+ monocytes in the ERS. CD4+ and CD8+ T cells decreased significantly and expressed high levels of inflammatory genes in the ERS. Among the B cells, the plasma cells increased remarkably, whereas the naïve B cells decreased. Our study identified several novel B cell-receptor (BCR) changes, such as IGHV3-23 and IGHV3-7, and confirmed isotypes (IGHV3-15, IGHV3-30, and IGKV3-11) previously used for virus vaccine development. The strongest pairing frequencies, IGHV3-23-IGHJ4, indicated a monoclonal state associated with SARS-CoV-2 specificity. Furthermore, integrated analysis predicted that IL-1β and M-CSF may be novel candidate target genes for inflammatory storm and that TNFSF13, IL-18, IL-2 and IL-4 may be beneficial for the recovery of COVID-19 patients. Our study provides the first evidence of an inflammatory immune signature in the ERS, suggesting that COVID-19 patients are still vulnerable after hospital discharge. Our identification of novel BCR signaling may lead to the development of vaccines and antibodies for the treatment of COVID-19.

Highlights

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The immune response was sustained for more than 7 days in the early recovery stage of COVID-19, suggesting that COVID-19 patients are still vulnerable after hospital discharge.

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Single-cell analysis revealed a predominant subset of CD14++ IL1β+ monocytes in patients in the ERS of COVID-19.

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Newly identified virus-specific B cell-receptor changes, such as IGHV3-23, IGHV3-7, IGHV3-15, IGHV3-30, and IGKV3-11, could be helpful in the development of vaccines and antibodies against SARS-CoV-2.

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IL-1β and M-CSF were discovered as novel mediators of inflammatory cytokine storm, and TNFSF13, IL-2, IL-4, and IL-18 may be beneficial for recovery.
Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome
Authors: Sims Matthew C , Mayer Louisa , Collins Janine H , Bariana Tadbir K , Megy Karyn , Lavenu-Bombled Cecile , Seyres Denis , Kollipara Laxmikanth , Burden Frances S , Greene Daniel , Lee Dave , Rodriguez-Romera Antonio , Alessi Marie-Christine , Astle William J , Bahou Wadie F , Bury Loredana , Chalmers Elizabeth , Da Silva Rachael , De Candia Erica , Deevi Sri V V , Farrow Samantha , Gomez Keith , Grassi Luigi , Greinacher Andreas , Gresele Paolo , Hart Dan , Hurtaud Marie-Françoise , Kelly Anne M , Kerr Ron , Quellec Sandra Le , Leblanc Thierry , Leinøe Eva B , Mapeta Rutendo , McKin-ney Harriet , Michelson Alan D , Morais Sara , Nugent Diane , Papadia Sofia , Park Soo J , Pasi John , Podda Gian Marco , Poon Man-Chiu , Reed Rachel , Sekhar Mallika , Shalev Hanna , Sivapalaratnam Suthesh , Steinberg-Shemer Orna , Stephens Jonathan C , Tait Robert C , Turro Ernest , Wu John K M , Zieger Barbara ,   NIHR BioResource, Kuijpers Taco W , Whetton Anthony D , Sickmann Albert , Freson Kathleen , Downes Kate , Erber Wendy N , Frontini Mattia , Nurden Paquita , Ouwehand Willem H , Favier Remi , Guerrero Jose A
Published: March 2020

Gray platelet syndrome (GPS) is a rare recessive disorder caused by variants in NBEAL2 and characterized by bleeding symptoms, the absence of platelet ɑ-granules, splenomegaly and bone marrow (BM) fibrosis. Due to its rarity, it has been difficult to fully understand the pathogenic processes that lead to these clinical sequelae. To discern the spectrum of pathological features, we performed a detailed clinical genotypic and phenotypic study of 47 GPS patients. We identified 33 new causal variants in NBEAL2. Our GPS patient cohort exhibited known phenotypes, including macro-thrombocytopenia, BM fibrosis, megakaryocyte emperipolesis of neutrophils, splenomegaly, and elevated serum vitamin B12 levels. We also observed novel clinical phenotypes; these include reduced leukocyte counts and increased presence of autoimmune disease and positive autoantibodies. There were widespread differences in the transcriptome and proteome of GPS platelets, neutrophils, monocytes, and CD4-lymphocytes. Proteins less abundant in these cells were enriched for constituents of granules, supporting a role for Nbeal2 in the function of these organelles across a wide range of blood cells. Proteomic analysis of GPS plasma showed increased levels of proteins associated with inflammation and immune response. One quarter of plasma proteins increased in GPS are known to be synthesized outside of hematopoietic cells, predominantly in the liver. In summary, our data demonstrate that, in addition to the well-described platelet defects in GPS, there are also immune defects. The abnormal immune cells may be the drivers of systemic abnormalities, such as autoimmune disease.
Serology characteristics of SARS-CoV-2 infection since the exposure and post symptoms onset
Authors: Lou Bin , Li Ting-Dong , Zheng Shu-Fa , Su Ying-Ying , Li Zhi-Yong , Liu Wei , Yu Fei , Ge Sheng-Xiang , Zou Qian-Da , Yuan Quan , Lin Sha , Hong Cong-Ming , Yao Xiang-Yang , Zhang Xue-Jie , Wu Ding-Hui , Zhou Guo-Liang , Hou Wang-Heng , Li Ting-Ting , Zhang Ya-Li , Zhang Shi-Yin , Fan Jian , Zhang Jun , Xia Ning-Shao , Chen Yu
Published: March 2020

Background

Timely diagnosis of SARS-CoV-2 infection is the prerequisite for treatment and preventive quarantine. The serology characteristics and complement diagnosis value of antibody test to RNA test needs to be demonstrated.

Method

A patient cohort study was conducted at the first affiliated hospital of Zhejiang University, China. Serial plasma of COVID-19 patients and were collected and total antibody (Ab), IgM and IgG antibody against SARS-CoV-2 were detected. The antibody dynamics during the infection were described.

Results

The seroconversion rate for Ab, IgM and IgG in COVID-19 patients was 98.8% (79/80), 93.8% (75/80) and 93.8% (75/80), respectively. The first detectible serology marker is total antibody and followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 day post exposure (d.p.e) or 9, 10 and 12 days post onset, separately. The antibody levels increased rapidly since 6 d.p.o and accompanied with the decline of viral load. For patients in the early stage of illness (0-7d.p.o),Ab showed the highest sensitivity (64.1%) compared to the IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG detection increased to 100%, 96.7% and 93.3% two weeks later, respectively.

Conclusions

Typical acute antibody response is induced during the SARS-CoV-2 infection. The serology testing provides important complementation to RNA test for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patient. It should be strongly recommended to apply well-validated antibody tests in the clinical management and public health practice to improve the control of COVID-19 infection.

Take-Home Message

Antibody responses are induced after SARS-CoV-2 infection and complement diagnosis value of antibody test to RNA test was observed. Antibody tests are critical tools in clinical management and control of SARS-CoV-2 infection and COVID-19.
Effects of episodic future thinking on temporal discounting: a re-analysis of six data sets using hierarchical Bayesian parameter estimation and compilation of effect sizes
Authors: Peters Jan , Brassen Stefanie , Bromberg Uli , Büchel Christian , Sasse Laura , Wiehler Antonius
Published: March 2020

Temporal discounting refers to the tendency of humans and many animals to devalue rewards as a function of time. Steep discounting of value over time is associated with a range of psychiatric disorders, including substance use disorders and behavioral addictions, and therefore of potentially high clinical relevance. One cognitive factor that has repeatedly been shown to reduce temporal discounting in humans is episodic future thinking, the process of vividly imagining future outcomes, which has been linked to hippocampal mechanisms in a number of studies. However, the analytical approaches used to quantify the behavioral effects have varied between studies, which complicates a direct comparison of the obtained effect sizes. Here we re-analyzed temporal discounting data from previously published functional magnetic resonance imaging (fMRI) and behavioral studies (six data sets from five papers, n=204 participants in total) using an identical model structure and hierarchical Bayesian parameter estimation procedure. Analyses confirmed that engagement in episodic future thinking leads to robust and and consistent reductions in temporal discounting with on average medium effect sizes. In contrast, effects on choice consistency (decision noise) where small and with inconsistent directionality. We provide standardized and unstandardized effect size estimates for each data set and discuss clinical implications as well as issues of hierarchical Bayesian parameter estimation.
Automatic Identification of SARS Coronavirus using Compression-Complexity Measures
Authors: Balasubramanian Karthi , Nagaraj Nithin
Published: March 2020

Abstract

Finding vaccine or specific antiviral treatment for global pandemic of virus diseases (such as the ongoing COVID-19) requires rapid analysis, annotation and evaluation of metagenomic libraries to enable a quick and efficient screening of nucleotide sequences. Traditional sequence alignment methods are not suitable and there is a need for fast alignment-free techniques for sequence analysis. Information theory and data compression algorithms provide a rich set of mathematical and computational tools to capture essential patterns in biological sequences. In 2013, our research group (Nagaraj et al., Eur. Phys. J. Special Topics 222(3-4), 2013) has proposed a novel measure known as Effort-To-Compress (ETC) based on the notion of compression-complexity to capture the information content of sequences. In this study, we propose a compression-complexity based distance measure for automatic identification of SARS coronavirus strains from a set of viruses using only short fragments of nucleotide sequences. We also demonstrate that our proposed method can correctly distinguish SARS-CoV-2 from SARS-CoV-1 viruses by analyzing very short segments of nucleotide sequences. This work could be extended further to enable medical practitioners in automatically identifying and characterizing SARS coronavirus strain in a fast and efficient fashion using short and/or incomplete segments of nucleotide sequences. Potentially, the need for sequence assembly can be circumvented.

Note

The main ideas and results of this research were first presented at theInternational Conference on Nonlinear Systems and Dynamics(CNSD-2013) held at Indian Institute of Technology, Indore, December 12, 2013. In this manuscript, we have extended our preliminary analysis to include SARS-CoV-2 virus as well.
Spontaneous recovery and the multiple timescales of human motor memory
Authors: Orozco Simon P. , Albert Scott T. , Shadmehr Reza
Published: March 2020

In numerous paradigms, from fear conditioning to motor adaptation, memory exhibits a remarkable property: acquisition of a novel behavior followed by its extinction results in spontaneous recovery of the original behavior. A current model suggests that spontaneous recovery occurs because learning is supported by two different adaptive processes: one fast (high error sensitivity, low retention), and the other slow (low error sensitivity, high retention). Here, we searched for signatures of these hypothesized processes in the commands that guided single movements. We examined human saccadic eye movements and observed that following experience of a visual error, there was an adaptive change in the motor commands of the subsequent saccade, partially correcting for the error. However, the error correcting commands were expressed only during the deceleration period. If the errors persisted, the acceleration period commands also changed. Adaptation of acceleration period commands exhibited poor sensitivity to error, but the learning was resistant to forgetting. In contrast, the deceleration period commands adapted with high sensitivity to error, and the learning suffered from poor retention. Thus, within a single saccade, a fast-like process influenced the deceleration period commands, whereas a slow-like process influenced the acceleration period commands. Following extinction training, with passage of time motor memory exhibited spontaneous recovery, as evidenced by return of saccade endpoints toward their initial adapted state. The temporal dynamics of spontaneous recovery suggested that a single saccade is controlled by two different adaptive controllers, one active during acceleration, and the other during deceleration.

Significance statement

A feature of memory in many paradigms is the phenomenon of spontaneous recovery: learning followed by extinction inevitably leads to reversion toward the originally learned behavior. A theoretical model posits that spontaneous recovery is a feature of memory systems that learn with two independent learning processes, one fast, and the other slow. However, there have been no direct measures of these putative processes. Here, we found potential signatures of the two independent adaptive processes during control of a single saccade. The results suggest that distinct adaptive controllers contribute to the acceleration and deceleration phases of a saccade, and that each controller is supported by a fast and a slow learning process.
Hepatic NFAT signaling regulates the expression of inflammatory cytokines in cholestasis
Authors: Cai Shi-Ying , Yu Dongke , Soroka Carol J. , Wang Jing , Boyer James L.
Published: March 2020

The inflammatory response plays an important role in cholestatic liver injury where bile acid (BA) induction of proinflammatory cytokines in hepatocytes is an initial pathophysiologic event. However, the signaling pathways involving BA stimulation of cytokine production remain to be elucidated. In this report, we examined the functional role of the Nuclear Factor of Activated T-cells (NFAT) in BA-induction of inflammatory genes in hepatic cells and cholestatic livers. We found that NFAT isoform c1 and c3 were expressed in human and mouse hepatocytes. When treated with cholestatic levels of BA, both human and mouse hepatocytes but not cholangiocytes increased NFATc3 nuclear translocation, associated with elevated mRNA levels of IL-8, Cxcl2, and Cxcl10 in these cells. Blocking NFAT activation with pathway-specific inhibitors (i.e. cyclosporine A, FK-506, KN-62 and Inca-6) or knocking down Nfatc3, significantly repressed BA-induction of these cytokines in mouse hepatocytes, including Ccl2, Cxcl2, Cxcl10, Icam1 and Egr1. Nuclear expression of NFATc3/Nfatc3 protein was also increased in cholestatic livers after bile duct ligation or in Abcb4-/-mice and in patients with primary biliary cholangitis and primary sclerosing cholangitis in association with tissue elevations of Cxcl2 and IL-8. Gene reporter assays and ChIP-PCR demonstrated that the NFAT response element in its promoter played a key role in BA-induced human IL-8 expression. Together our findings indicate that NFAT plays an important role in BA stimulation of hepatic cytokines in cholestasis and is a mechanism that may provide novel targets to reduce cholestatic liver injury.
Capacity of short-term memory in dyslexia is reduced due to less efficient utilization of items’ long-term frequency
Authors: Kimel Eva , Lieder Itay , Ahissar Merav
Published: March 2020

Dyslexia, defined as a specific impairment in decoding the written script, is the most widespread learning difficulty. However, individuals with dyslexia (IDDs) also consistently manifest reduced short-term memory (STM) capacity, typically measured by Digit Span or non-word repetition tasks. In this paper we report two experiments which test the effect of item frequency and the effect of a repeated sequence on the performance in STM tasks in good readers and in IDDs. IDDs’ performance benefited less from item frequency, revealing poor use of long-term single item statistics. This pattern suggests that the amply reported shorter verbal spans in dyslexia may in fact reflect their impaired sensitivity to items’ long-term frequency. For repeated sequence learning, we found no significant deficit among IDDs, even when a sensitive paradigm and a robust measure were used.
Changes in the blood plasma lipidome associated with response to atypical antipsychotic treatments in schizophrenia
Authors: de Almeida Valéria , Alexandrino Guilherme L. , Aquino Adriano , Gomes Alexandre F. , Murgu Michael , Guest Paul C. , Steiner Johann , Martins-de-Souza Daniel
Published: March 2020

Atypical antipsychotics are widely used to manage schizophrenia symptoms. However, these drugs can induce deleterious side effects, such as MetS, which are associated with an increased cardiovascular risk to patients. Lipids play a central role in this context, and changes in lipid metabolism have been implicated in schizophrenia’s pathobiology. Furthermore, recent evidence suggests that lipidome changes may be related to antipsychotic treatment response. The aim of this study was to evaluate the lipidome changes in blood plasma samples of schizophrenia patients before and after 6 weeks of treatment with either risperidone, olanzapine, or quetiapine. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis showed changes in the levels of ceramides (Cer), glycerophosphatidic acids (PA), glycerophosphocholines (PC), phosphatidylethanolamines (PE), phosphatidylinositols (PI), glycerophosphoglycerols (PG), and phosphatidylserines (PS) for all treatments. However, the treatment with risperidone also affected diacylglycerides (DG), ceramide 1-phosphates (CerP), triglycerides (TG), sphingomyelins (SM), and ceramide phosphoinositols (PI-Cer). Moreover, specific lipid profiles were observed that could be used to distinguish poor and good responders to the different antipsychotics. As such, further work in this area may lead to lipid-based biomarkers that could be used to improve the clinical management of schizophrenia patients.
Non-selective inhibition of the motor system following unexpected and expected infrequent events
Authors: Iacullo Carly , Diesburg Darcy A. , Wessel Jan R.
Published: March 2020

Motor inhibition is a key control mechanism that allows humans to rapidly adapt their actions in response to environmental events. One of the hallmark signatures of rapidly exerted, reactive motor inhibition is the non-selective suppression of cortico-spinal excitability (CSE): unexpected sensory stimuli lead to a suppression of CSE across the entire motor system, even in muscles that are inactive. Theories suggest that this reflects a fast, automatic, and broad engagement of inhibitory control, which facilitates behavioral adaptations to unexpected changes in the sensory environment. However, it is an open question whether such non-selective CSE suppression is truly due to the unexpected nature of the sensory event, or whether it is sufficient for an event to be merely infrequent (but not unexpected). Here, we report data from two experiments in which human subjects experienced both unexpected and expected infrequent events during a simple reaction time task while CSE was measured from a task-unrelated muscle. We found that expected infrequent events can indeed produce non-selective CSE suppression – but only when they occur during movement initiation. In contrast, unexpected infrequent events produce non-selective CSE suppression even in the absence of movement initiation. Moreover, CSE suppression due to unexpected events occurs at shorter latencies compared to expected infrequent events. These findings demonstrate that unexpectedness and stimulus infrequency have qualitatively different suppressive effects on the motor system. They also have key implications for studies that seek to disentangle neural and psychological processes related to motor inhibition and stimulus detection.
Glycyrrhizic acid improves cognitive levels of aging mice by regulating T/B cell proliferation
Authors: Jiang Ruichan , Gao Jiaming , Shen Junyan , Zhu Xiaoqi , Wang Hao , Feng Shengyu , Huang Ce , Shen Haitao , Liu Hailiang
Published: March 2020

Dear Editor,

Licorice is the root ofGlycyrrhiza glabraL. (Leguminosae), which grows in various warm climates such as the Middle East, Asia, and Southern Europe. It is one of the oldest known medicinal herbs and is referred to as “the father of herbal medicine.” Glycyrrhizic acid (GA) (Fig. 1A), a triterpenoid saponin, is a major component of licorice. It has a variety of pharmacological activities such as anti-inflammatory, antioxidant, anticancer, neuroprotective, and immune effects, among others.[1]. Previous studies indicated that GA produces robust neuroprotection via the modulation of anti-apoptotic and pro-apoptotic factors, primarily through the ERK signaling pathway and its anti-inflammatory properties against high-mobility group box 1 phosphorylation and the suppression of inflammatory cytokine induction[2-4]. These results were based on pathological models. Although numerous pathways have been implicated in the neuroprotective effects of GA, the molecular mechanisms are not yet completely understood. In this study, we aimed to investigate the effects of GA in preventing age-related immune involution and cognitive disorders, the relationship between immune involution and cognition, and the underlying molecular mechanisms.
Unhealthy Behaviours and Parkinson’s Disease: A Mendelian Randomisation Study
Authors: Heilbron Karl , Jensen Melanie P. , Bandres-Ciga Sara , Fontanillas Pierre ,   The 23andMe Research Team, Blauwendraat Cornelis , Nalls Mike A. , Singleton Andrew B. , Smith George Davey , Cannon Paul , Noyce Alastair
Published: March 2020

Objective

Tobacco smoking, alcohol intake, and high BMI have been identified in observational studies as potentially protective factors against developing Parkinson’s disease (PD). Because of the possibility of residual confounding and reverse causation, it is unclear whether such epidemiological associations are causal. Mendelian randomisation (MR) uses genetic variants to explore causal effects of exposures on outcomes; minimising these sources of bias. Using MR, this study sought to determine the causal relationship between tobacco smoking, alcohol intake, and high BMI, and the risk of PD.

Methods

We performed genome-wide association studies to identify single nucleotide polymorphisms associated with the exposures. MR analysis of the relationship between each exposure and PD was undertaken using a split-sample design. The inverse variance weighted (IVW) method was used to combine SNP-specific effect estimates.

Results

Ever-smoking causally reduced risk of PD (OR 0.955; 95% confidence interval [CI] 0.921-0.991; p=0.013). An increase in daily alcohol intake causally increased risk of PD (OR 1.125, 95% CI 1.025-1.235; p=0.013) and a 1 kg/m2BMI causally reduced risk of PD (OR 0.988, 95% CI 0.979-0.997; p=0.008). Sensitivity analyses did not suggest bias from horizontal pleiotropy or invalid instruments.

Interpretation

Using split-sample MR in over 2.4 million participants, we observed a protective effect of smoking on risk of PD, warranting the prioritisation of related therapeutic targets, such as nicotinic agonists, in prevention trials. In contrast to observational data, alcohol consumption causally increased risk of PD. Higher BMI had a protective effect on PD, but the effect was small.
Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis
Authors: Alqahtani Jaber S. , Oyelade Tope , Aldhahir Abdulelah M. , Alghamdi Saeed M. , Almehmadi Mater , Alqahtani Abdullah S , Quaderi Shumonta , Mandal Swapna , Hurst John R.
Published: March 2020

Background

Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020. No studies have yet summarised the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.

Methods

We systematically searched electronic databases from inception to March 24, 2020. Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study quality was assessed using a modified version of the Newcastle-Ottawa Scale. We synthesised a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).

Results

In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed. A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients. All studies were included in the meta-analysis. The crude case fatality rate of COVID-19 was 6.4%. The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%–3%) and 9% (95% CI, 4%–14%) respectively. COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4– 2.4)]. This was associated with higher mortality (60%). Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications. The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03–2.04] to have severe complications compared to former and never smokers. Current smokers also had a higher mortality rate of 38.5%.

Conclusion

Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD. Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate. Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers.
Attentional Focus Modulates Automatic Finger-tapping Movements
Authors: Zhang Xilei. , Jiang Xingxun. , Yuan Xiangyong. , Zheng Wenming.
Published: March 2020

The majority of human behaviors are composed of automatic movements (e.g., walking or finger-tapping) which are learned during nurturing and can be performed simultaneously without interfering with other tasks. One critical and yet to be examined assumption is that the attention system has the innate capacity to modulate automatic movements. The present study tests this assumption. Setting no deliberate goals for movement, we required sixteen participants to perform personalized and well-practiced finger-tapping movements in three experiments while focusing their attention on either different component fingers or away from movements. Using cutting-edge pose estimation techniques to quantify tapping trajectory, we showed that attention to movement can disrupt movement automaticity, as indicated by decreased inter-finger and inter-trial temporal coherence; facilitate the attended and inhibit the unattended movements in terms of tapping amplitude; and re-organize the action sequence into distinctive patterns according to the focus of attention. These findings demonstrate compelling evidence that attention can modulate automatic movements and provide an empirical foundation for theories based on such modulation in controlling human behavior.
A comparison study of SARS-CoV-2 IgG antibody between male and female COVID-19 patients: a possible reason underlying different outcome between gender
Authors: Zeng Fanfan , Dai Chan , Cai Pengcheng , Wang Jinbiao , Xu Lei , Li Jianyu , Hu Guoyun , Wang Lin
Published: March 2020

Objective

To compare the difference of SARS-CoV-2 IgG antibody between male and female COVID-19 patients and figure out a possible explanation for different outcome between male and female patients.

Methods

A total number of 331 patients confirmed SARS-CoV-2 infection were enrolled. The plasma of these patients were collected during hospitalization and were detected for SARS-CoV-2 IgG antibody. Afterwards, the difference of IgG antibody between male and female patients was analyzed.

Results

The level of IgG antibody in mild, general and recovering patients showed on difference between male and female. In severe status, the average IgG antibody level in female patients tended to be higher than that of in male patients. Compared with male patients, most of the female patients generated a relatively high level of SARS-CoV-2 IgG antibody in severe status. In addition, the generation of IgG antibody in female tended to be stronger than male patients in disease early phase.

Conclusions

The inconsistent of SARS-CoV-2 IgG antibody generation in male and female patients may account for the different outcome of COVID-19 between gender.
A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface
Authors: Castro Danielle Karoline Silva do Vale , da Silva Sabrina Matos de Oliveira , Pereira Humberto D'Muniz , Macedo Joci Neuby Alves , Leonardo Diego Antonio , Valadares Napoleão Fonseca , Kumagai Patricia Suemy , Brandão-Neto José , Araújo Ana Paula Ulian , Garratt Richard Charles
Published: March 2020

Human septins 3, 9 and 12 are the only members of a specific subgroup of septins that display several unusual features, including the absence of a C-terminal coiled coil. This particular subgroup (the SEPT3 septins) are present in rod-like octameric protofilaments but are lacking in similar hexameric assemblies, which only contain representatives of the three remaining subgroups. Both hexamers and octamers can self-assemble into mixed filaments by end-to-end association, implying that the SEPT3 septins may facilitate polymerization but not necessarily function. These filaments frequently associate into higher order complexes which associate with biological membranes, triggering a wide range of cellular events. In the present work, a complete compendium of crystal structures for the GTP-binding domains of all of the SEPT3 subgroup members when bound to either GDP or to a GTP analogue is provided. The structures reveal a unique degree of plasticity at one of the filamentous interfaces (dubbed NC). Specifically, structures of the GDP and GTPγS complexes of SEPT9 reveal a squeezing mechanism at the NC interface which would expel a polybasic region from its binding site and render it free to interact with negatively charged membranes. On the other hand, a polyacidic region associated with helix α5′, the orientation of which is particular to this subgroup, provides a safe haven for the polybasic region when retracted within the interface. Together, these results suggest a mechanism which couples GTP binding and hydrolysis to membrane association and implies a unique role for the SEPT3 subgroup in this process. These observations can be accounted for by constellations of specific amino-acid residues that are found only in this subgroup and by the absence of the C-terminal coiled coil. Such conclusions can only be reached owing to the completeness of the structural studies presented here.
Crystal structure, Hirshfeld surface and frontier molecular orbital analysis of 10-benzyl-9-(3-ethoxy-4-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione
Authors: Suresh Babu N. , Sughanya V. , Dhandapani A. , Kalaivanan R.
Published: March 2020

In the fused ring system of the title compound, C32H37NO4, the central dihydropyridine ring adopts a flattened boat conformation, the mean and maximum deviations of the dihydropyridine ring being 0.1429 (2) and 0.2621 (2) Å, respectively. The two cyclohexenone rings adopt envelope conformations with the tetrasubstituted C atoms as flap atoms. The benzene and phenyl rings form dihedral angles of 85.81 (2) and 88.90 (2)°, respectively, with the mean plane of the dihydropyridine ring. In the crystal, molecules are linked via an O—H...O hydrogen bond, forming a helical chain along the b-axis direction. A Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H...H (65.2%), O...H/H...O (18.8%) and C...H/H...C (13.9%) contacts. Quantum chemical calculations for the frontier molecular orbitals were undertake to determine the chemical reactivity of the title compound.
Poly[(μ4-5,7-dihydro-1H,3H-dithieno[3,4-b:3′,4′-e]pyrazine-κ4
N:N′:S:S′)tetra-μ3-iodido-tetracopper]: a three-dimensional copper(I) coordination polymer
Authors: Assoumatine Tokouré , Stoeckli-Evans Helen
Published: March 2020

The reaction of ligand 5,7-dihydro-1H,3H-dithieno[3,4-b:3′,4′-e]pyrazine (L) with CuI lead to the formation of a three-dimensional coordination polymer, incorporating the well known [Cu
x
I
x
]
n
staircase motif (x = 4). These polymer [Cu4I4]
n
chains are linked via the N and S atoms of the ligand to form the three-dimensional coordination polymer poly[(μ4-5,7-dihydro-1H,3H-dithieno[3,4-b:3′,4′-e]pyrazine-κ4
N:N′:S:S′)tetra-μ3-iodido-tetracopper], [Cu4I4(C8H8N2S2)]
n
(I). The asymmetric unit is composed of half a ligand molecule, with the pyrazine ring located about a center of symmetry, and two independent copper(I) atoms and two independent I− ions forming the staircase motif via centers of inversion symmetry. The framework is consolidated by C—H...I hydrogen bonds.
AESA radar and IRST against low observable threats
Authors: Gaitanakis George-Konstantinos , Limnaios George , Zikidis Konstantinos
Published: March 2020

Purpose

Modern fighter aircraft using active electronically scanned array (AESA) fire control radars are able to detect and track targets at long ranges, in the order of 50 nautical miles or more. Low observable or stealth technology has contested the radar capabilities, reducing detection/tracking ranges roughly to one-third (or even less, for fighter aircraft radar). Hence, infrared search and track (IRST) systems have been reconsidered as an alternative to the radar. This study aims to explore and compare the capabilities and limitations of these two technologies, AESA radars and IRST systems, as well as their synergy through sensor fusion.

Design/methodology/approach

The AESA radar range is calculated with the help of the radar equation under certain assumptions, taking into account heat dissipation requirements, using the F-16 fighter as a case study. Concerning the IRST sensor, a new model is proposed for the estimation of the detection range, based on the emitted infrared radiation caused by aerodynamic heating.

Findings

The maximum detection range provided by an AESA radar could be restricted because of the increased waste heat which is produced and the relevant constraints concerning the cooling capacity of the carrying aircraft. On the other hand, IRST systems exhibit certain advantages over radars against low observable threats. IRST could be combined with a datalink with the help of data fusion, offering weapons-quality track.

Originality/value

An original approach is provided for the IRST detection range estimation. The AESA/IRST comparison offers valuable insight, while it allows for more efficient planning, at the military acquisition phase, as well as at the tactical level.
Adoption of smart technologies and circular economy performance of buildings
Authors: Windapo Abimbola Oluwakemi , Moghayedi Alireza
Published: March 2020

Purpose

This paper examines the use of intelligent technologies in buildings and whether the use of smart technologies impacts the circular economy performance of buildings in terms of energy and water consumption, their marginal cost and the management decision time and quality, for building management companies.

Design/methodology/approach

The study is initiated through the detailed build-up of the proposition that employs a systematic literature review and adopts the case study research design to make a cross-case analysis of the information extracted from data. The data are derived from the operating costs of two buildings in which most advanced smart technologies are used in Cape Town and interviews with their facility managers. These data provide two research case studies. The results of the investigation are then analysed and linked back to the literature.

Findings

The results of the research suggest that the implementation of smart technologies to create intelligent infrastructure is beneficial to the circular economy performance of buildings and the time taken for management decisions. The results of the study have proven that the impact of smart technologies on the circular economy performance of buildings is positive, as it lowers the cost of utilities and decreases the time required for management decisions.

Research limitations/implications

The research reported in this paper is exploratory, and due to its limited sample size, its findings may not be statistically generalizable to the population of high-occupancy buildings in Cape Town, which incorporate smart infrastructure technologies within their building management systems (BMSs). Also, the empirical data collected were limited to the views and opinions of the interviewees, and the secondary data were obtained from the selected buildings.

Practical implications

The findings suggest that investment in smart technologies within buildings is of significant value and will improve the circular economy performance of buildings in terms of low energy and water use, and effective management decisions.

Social implications

The results imply that there would be more effective maintenance decisions taken by facilities managers, which will enable the maintenance of equipment to be properly monitored, problems with the building services and equipment to be identified in good time and in improved well-being and user satisfaction.

Originality/value

The study provides evidence to support the concept that advanced smart technologies boost performance, the time required for management decisions and that they enable circularity in buildings. It supports the proposition that investment in the more advanced smart technologies in buildings has more positive rewards.
Agricultural product price forecasting methods: research advances and trend
Authors: Wang Luyao , Feng Jianying , Sui Xiaojie , Chu Xiaoquan , Mu Weisong
Published: March 2020

Purpose

The purpose of this paper is to provide reference for researchers by reviewing the research advances and trend of agricultural product price forecasting methods in recent years.

Design/methodology/approach

This paper reviews the main research methods and their application of forecasting of agricultural product prices, summarizes the application examples of common forecasting methods, and prospects the future research directions.

Findings

1) It is the trend to use hybrid models to predict agricultural products prices in the future research; 2) the application of the prediction model based on price influencing factors should be further expanded in the future research; 3) the performance of the model should be evaluated based on DS rather than just error-based metrics in the future research; 4) seasonal adjustment models can be applied to the difficult seasonal forecasting tasks in the agriculture product prices in the future research; 5) hybrid optimization algorithm can be used to improve the prediction performance of the model in the future research.

Originality/value

The methods from this paper can provide reference for researchers, and the research trends proposed at the end of this paper can provide solutions or new research directions for relevant researchers.