bluuebunny/crossref_metadata_2025 huggingface dataset:
Prehospital Identification of Large Vessel Occlusions Using Modified National Institutes of Health Stroke Scale: A Pilot Study
Authors: Mulkerin William D. , Spokoyny Ilanit , Francisco Jonathan T. , Lima Brandon , Corry Megan D. , Nudelman Matthew J. R. , Niknam Kian , Brown Ian P. , Kohn Michael A. , Govindarajan Prasanthi
Published: May 2021

Stroke identification is a key step in acute ischemic stroke management. Our objectives were to prospectively examine the agreement between prehospital and hospital Modified National Institutes of Health Stroke Scale (mNIHSS) assessments as well as assess the prehospital performance characteristics of the mNIHSS for identification of large vessel occlusion strokes.

Method: In this prospective cohort study conducted over a 20-month period (11/2016–6/2018), we trained 40 prehospital providers (paramedics) in Emergency Neurological Life Support (ENLS) curriculum and in mNIHSS. English-speaking patients aged 18 and above transported for an acute neurological deficit were included. Using unique identifiers, we linked the prehospital assessment records to the hospital record. We calculated the agreement between prehospital and hospital mNIHSS scores using the Bland-Altman analysis and the sensitivity and specificity of the prehospital mNIHSS.

Results: Of the 31 patients, the mean difference (prehospital mNIHSS—hospital mNIHSS) was 2.4, 95% limits of agreement (−5.2 to 10.0); 10 patients (32%) met our a priori imaging definition of large vessel occlusion and the sensitivity of mNIHSS ≥ 8 was 6/10 or 0.60 (95% CI: 0.26–0.88) and the specificity was 13/21 or 0.62 (95% CI: 0.38–0.82), respectively.

Conclusions: We were able to train prehospital providers to use the prehospital mNIHSS. Prehospital and hospital mNIHSS had a reasonable level of agreement and and the scale was able to predict large vessel occlusions with moderate sensitivity.
Glial Purinergic Signaling in Neurodegeneration
Authors: Pietrowski Marie J. , Gabr Amr Ahmed , Kozlov Stanislav , Blum David , Halle Annett , Carvalho Kevin
Published: May 2021

Purinergic signaling regulates neuronal and glial cell functions in the healthy CNS. In neurodegenerative diseases, purinergic signaling becomes dysregulated and can affect disease-associated phenotypes of glial cells. In this review, we discuss how cell-specific expression patterns of purinergic signaling components change in neurodegeneration and how dysregulated glial purinergic signaling and crosstalk may contribute to disease pathophysiology, thus bearing promising potential for the development of new therapeutical options for neurodegenerative diseases.
Ulnar Neuropathy at the Elbow: From Ultrasound Scanning to Treatment
Authors: Mezian Kamal , Jačisko Jakub , Kaiser Radek , Machač Stanislav , Steyerová Petra , Sobotová Karolína , Angerová Yvona , Naňka Ondřej
Published: May 2021

Ulnar neuropathy at the elbow (UNE) is commonly encountered in clinical practice. It results from either static or dynamic compression of the ulnar nerve. While the retroepicondylar groove and its surrounding structures are quite superficial, the use of ultrasound (US) imaging is associated with the following advantages: (1) an excellent spatial resolution allows a detailed morphological assessment of the ulnar nerve and adjacent structures, (2) dynamic imaging represents the gold standard for assessing the ulnar nerve stability in the retroepicondylar groove during flexion/extension, and (3) US guidance bears the capability of increasing the accuracy and safety of injections. This review aims to illustrate the ulnar nerve's detailed anatomy at the elbow using cadaveric images to understand better both static and dynamic imaging of the ulnar nerve around the elbow. Pathologies covering ulnar nerve instability, idiopathic cubital tunnel syndrome, space-occupying lesions (e.g., ganglion, heterotopic ossification, aberrant veins, and anconeus epitrochlearis muscle) are presented. Additionally, the authors also exemplify the scientific evidence from the literature supporting the proposition that US guidance is beneficial in injection therapy of UNE. The non-surgical management description covers activity modifications, splinting, neuromobilization/gliding exercise, and physical agents. In the operative treatment description, an emphasis is put on two commonly used approaches—in situ decompression and anterior transpositions.
Hemorrhagic Transformation in Ischemic Stroke and the Role of Inflammation
Authors: Spronk Elena , Sykes Gina , Falcione Sarina , Munsterman Danielle , Joy Twinkle , Kamtchum-Tatuene Joseph , Jickling Glen C.
Published: May 2021

Hemorrhagic transformation (HT) is a common complication in patients with acute ischemic stroke. It occurs when peripheral blood extravasates across a disrupted blood brain barrier (BBB) into the brain following ischemic stroke. Preventing HT is important as it worsens stroke outcome and increases mortality. Factors associated with increased risk of HT include stroke severity, reperfusion therapy (thrombolysis and thrombectomy), hypertension, hyperglycemia, and age. Inflammation and the immune system are important contributors to BBB disruption and HT and are associated with many of the risk factors for HT. In this review, we present the relationship of inflammation and immune activation to HT in the context of reperfusion therapy, hypertension, hyperglycemia, and age. Differences in inflammatory pathways relating to HT are discussed. The role of inflammation to stratify the risk of HT and therapies targeting the immune system to reduce the risk of HT are presented.
Recurrent Traumatic Brain Injury Surveillance Using Administrative Health Data: A Bayesian Latent Class Analysis
Authors: Lasry Oliver , Dendukuri Nandini , Marcoux Judith , Buckeridge David L.
Published: May 2021

Background: The initial injury burden from incident TBI is significantly amplified by recurrent TBI (rTBI). Unfortunately, research assessing the accuracy to conduct rTBI surveillance is not available. Accurate surveillance information on recurrent injuries is needed to justify the allocation of resources to rTBI prevention and to conduct high quality epidemiological research on interventions that mitigate this injury burden. This study evaluates the accuracy of administrative health data (AHD) surveillance case definitions for rTBI and estimates the 1-year rTBI incidence adjusted for measurement error.

Methods: A 25% random sample of AHD for Montreal residents from 2000 to 2014 was used in this study. Four widely used TBI surveillance case definitions, based on the International Classification of Disease and on radiological exams of the head, were applied to ascertain suspected rTBI cases. Bayesian latent class models were used to estimate the accuracy of each case definition and the 1-year rTBI measurement-error-adjusted incidence without relying on a gold standard rTBI definition that does not exist, across children (<18 years), adults (18-64 years), and elderly (> =65 years).

Results: The adjusted 1-year rTBI incidence was 4.48 (95% CrI 3.42, 6.20) per 100 person-years across all age groups, as opposed to a crude estimate of 8.03 (95% CrI 7.86, 8.21) per 100 person-years. Patients with higher severity index TBI had a significantly higher incidence of rTBI compared to patients with lower severity index TBI. The case definition that identified patients undergoing a radiological examination of the head in the context of any traumatic injury was the most sensitive across children [0.46 (95% CrI 0.33, 0.61)], adults [0.79 (95% CrI 0.64, 0.94)], and elderly [0.87 (95% CrI 0.78, 0.95)]. The most specific case definition was the discharge abstract database in children [0.99 (95% CrI 0.99, 1.00)], and emergency room visits claims in adults/elderly [0.99 (95% CrI 0.99, 0.99)]. Median time to rTBI was the shortest in adults (75 days) and the longest in children (120 days).

Conclusion: Conducting accurate surveillance and valid epidemiological research for rTBI using AHD is feasible when measurement error is accounted for.
Prefrontal Cortex Activation During Motor Sequence Learning Under Interleaved and Repetitive Practice: A Two-Channel Near-Infrared Spectroscopy Study
Authors: Immink Maarten A. , Pointon Monique , Wright David L. , Marino Frank E.
Published: May 2021

Training under high interference conditions through interleaved practice (IP) results in performance suppression during training but enhances long-term performance relative to repetitive practice (RP) involving low interference. Previous neuroimaging work addressing this contextual interference effect of motor learning has relied heavily on the blood-oxygen-level-dependent (BOLD) response using functional magnetic resonance imaging (fMRI) methodology resulting in mixed reports of prefrontal cortex (PFC) recruitment under IP and RP conditions. We sought to clarify these equivocal findings by imaging bilateral PFC recruitment using functional near-infrared spectroscopy (fNIRS) while discrete key pressing sequences were trained under IP and RP schedules and subsequently tested following a 24-h delay. An advantage of fNIRS over the fMRI BOLD response is that the former measures oxygenated and deoxygenated hemoglobin changes independently allowing for assessment of cortical hemodynamics even when there is neurovascular decoupling. Despite slower sequence performance durations under IP, bilateral PFC oxygenated and deoxygenated hemoglobin values did not differ between practice conditions. During test, however, slower performance from those previously trained under RP coincided with hemispheric asymmetry in PFC recruitment. Specifically, following RP, test deoxygenated hemoglobin values were significantly lower in the right PFC. The present findings contrast with previous behavioral demonstrations of increased cognitive demand under IP to illustrate a more complex involvement of the PFC in the contextual interference effect. IP and RP incur similar levels of bilateral PFC recruitment, but the processes underlying the recruitment are dissimilar. PFC recruitment during IP supports action reconstruction and memory elaboration while RP relies on PFC recruitment to maintain task variation information in working memory from trial to trial. While PFC recruitment under RP serves to enhance immediate performance, it does not support long-term performance.
Comparative Neurology of Circadian Photoreception: The Retinohypothalamic Tract (RHT) in Sighted and Naturally Blind Mammals
Authors: Hannibal Jens
Published: May 2021

The mammalian eye contains two systems for light perception: an image detecting system constituted primarily of the classical photoreceptors, rods and cones, and a non-image forming system (NIF) constituted of a small group of intrinsically photosensitive retinal ganglion cells driven by melanopsin (mRGCs). The mRGCs receive input from the outer retina and NIF mediates light entrainment of circadian rhythms, masking behavior, light induced inhibition of nocturnal melatonin secretion, pupillary reflex (PLR), and affect the sleep/wake cycle. This review focuses on the mammalian NIF and its anatomy in the eye as well as its neuronal projection to the brain. This pathway is known as the retinohypothalamic tract (RHT). The development and functions of the NIF as well as the knowledge gained from studying gene modified mice is highlighted. Furthermore, the similarities of the NIF between sighted (nocturnal and diurnal rodent species, monkeys, humans) and naturally blind mammals (blind mole ratsSpalax ehrenbergiand the Iberian mole,Talpa occidentalis) are discussed in relation to a changing world where increasing exposure to artificial light at night (ALAN) is becoming a challenge for humans and animals in the modern society.
ACTB Methylation in Blood as a Potential Marker for the Pre-clinical Detection of Stroke: A Prospective Nested Case-Control Study
Authors: Liu Chunlan , Yin Qiming , Li Mengxia , Fan Yao , Shen Chong , Yang Rongxi
Published: May 2021

Background

Stroke is the second leading cause of death worldwide. If risk of stroke could be evaluated early or even at a preclinical stage, the mortality rate could be reduced dramatically. However, the identified genetic factors only account for 5–10% of the risk of stroke. Studies on the risk factors of stroke are urgently needed. We investigated the correlation between blood-based β-actin (ACTB) methylation and the risk of stroke in a prospective nested case-control study.

Methods

The methylation level of ACTB was quantitatively determined by mass spectrometry in 139 stroke cases who developed stroke within 2 years after recruitment and 147 age- and sex-matched controls who remained stroke-free in a median follow-up of 2.71 years.

Results

We observed a highly significant correlation between hypomethylation of one CpG site of ACTB and increased risk of stroke in an onset-time-dependent manner (for onset time ≤ 1.5 years: odds ratio (OR) per + 10% methylation = 0.76, P = 0.001; for onset time ≤ 1.32 years: OR per + 10% methylation = 0.59, P = 7.82 × 10–7; for onset time ≤ 1 year: OR per + 10% methylation = 0.43, P = 3.00 × 10–6), and the increased cumulative incidence of stroke (log-rank P = 3.13 × 10–7). Neighboring CpG sites showed an inverse correlation with age and drinking status in controls (P < 0.05) but not in stroke cases.

Conclusion

We firstly reported the blood-based ACTB methylation as a marker for the risk evaluation and preclinical detection of stroke, which can be further modified by age and drinking.
Detection and Grading of Gliomas Using a Novel Two-Phase Machine Learning Method Based on MRI Images
Authors: Chen Tao , Xiao Feng , Yu Zunpeng , Yuan Mengxue , Xu Haibo , Lu Long
Published: May 2021

The early detection and grading of gliomas is important for treatment decision and assessment of prognosis. Over the last decade numerous automated computer analysis tools have been proposed, which can potentially lead to more reliable and reproducible brain tumor diagnostic procedures. In this paper, we used the gradient-based features extracted from structural magnetic resonance imaging (sMRI) images to depict the subtle changes within brains of patients with gliomas. Based on the gradient features, we proposed a novel two-phase classification framework for detection and grading of gliomas. In the first phase, the probability of each local feature being related to different types (e.g., diseased or healthy for detection, benign or malignant for grading) was calculated. Then the high-level feature representing the whole MRI image was generated by concatenating the membership probability of each local feature. In the second phase, the supervised classification algorithm was used to train a classifier based on the high-level features and patient labels of the training subjects. We applied this framework on the brain imaging data collected from Zhongnan Hospital of Wuhan University for glioma detection, and the public TCIA datasets including glioblastomas (WHO IV) and low-grade gliomas (WHO II and III) data for glioma grading. The experimental results showed that the gradient-based classification framework could be a promising tool for automatic diagnosis of brain tumors.
Multi-Dimensional Transcriptome Analysis Reveals Modulation of Cholesterol Metabolism as Highly Integrated Response to Brain Injury
Authors: Gourain Victor , Armant Olivier , Lübke Luisa , Diotel Nicolas , Rastegar Sepand , Strähle Uwe
Published: May 2021

Zebrafish is an attractive model to investigate regeneration of the nervous system. Despite major progress in our understanding of the underlying processes, the transcriptomic changes are largely unknown. We carried out a computational analysis of the transcriptome of the regenerating telencephalon integrating changes in the expression of mRNAs, their splice variants and investigated the putative role of regulatory RNAs in the modulation of these transcriptional changes. Profound changes in the expression of genes and their splice variants engaged in many distinct processes were observed. Differential transcription and splicing are important processes in response to injury of the telencephalon. As exemplified by the coordinated regulation of the cholesterol synthesizing enzymes and transporters, the genome responded to injury of the telencephalon in a multi-tiered manner with distinct and interwoven changes in expression of enzymes, transporters and their regulatory molecules. This coordinated genomic response involved a decrease of the mRNA of the key transcription factor SREBF2, induction of microRNAs (miR-182,miR-155,miR-146,miR-31) targeting cholesterol genes, shifts in abundance of splice variants as well as regulation of long non-coding RNAs. Cholesterol metabolism appears to be switched from synthesis to relocation of cholesterol. Based on ourin silicoanalyses, this switch involves complementary and synergistic inputs by different regulatory principles. Our studies suggest that adaptation of cholesterol metabolism is a key process involved in regeneration of the injured zebrafish brain.
Identification of Mutator-Derived Alternative Splicing Signatures of Genomic Instability for Improving the Clinical Outcome of Cholangiocarcinoma
Authors: Lin Zijing , Gong Jianping , Zhong Guochao , Hu Jiejun , Cai Dong , Zhao Lei , Zhao Zhibo
Published: May 2021

Background

Cholangiocarcinoma is an aggressive carcinoma with increasing incidence and poor outcomes worldwide. Genomic instability and alternative splicing (AS) events are hallmarks of carcinoma development and progression. The relationship between genomic instability, AS events, and tumor immune microenvironment remain unclear.

Methods

The splicing profiles of patients with cholangiocarcinoma were obtained from The Cancer Genome Atlas (TCGA) spliceSeq database. The transcriptomics, simple nucleotide variation (SNP) and clinical data of patients with cholangiocarcinoma were obtained from TCGA database. Patients were divided into genomic unstable (GU-like) and genomic stable (GS-like) groups according to their somatic mutations. Survival-related differential AS events were identified through integrated analysis of splicing profiling and clinical data. Kyoto Encyclopedia of Genes and Genomes enrichment analysis was used to identify AS events occurring in genes enriched in cancer pathways. Pearson correlation was applied to analyze the splicing factors regulating AS events. CIBERSORT was used identify differentially infiltrating immune cells.

Results

A prognostic signature was constructed with six AS events. Using this signature, the hazard ratio of risk score for overall survival is 2.362. For TCGA patients with cholangiocarcinoma, the area under the receiver operating characteristic curve is 0.981. CDK11A is a negative regulator of survival associated AS events. Additionally, the CD8+ T cell proportion and PD-L1 expression are upregulated in patients with cholangiocarcinoma and high splicing signatures.

Conclusion

We provide a prognostic signature for cholangiocarcinoma overall survival. The CDK11A splicing factor and SLC46A1-39899-ES and IARS-86836-ES AS events may be potential targets for cholangiocarcinoma therapy. Patients with high AS risk score may be more sensitive to anti-PD-L1/PD1 immunotherapy.
The Prognostic Value of Preoperative Systemic Inflammatory Response Index (SIRI) in Patients With High-Grade Glioma and the Establishment of a Nomogram
Authors: He Qian , Li Longhao , Ren Qinglan
Published: May 2021

Background

The predictive value of systemic inflammatory response index (SIRI) was confirmed in some malignant tumors. However, few studies investigated the prognostic value of SIRI in high-grade gliomas. This study aimed to evaluate the prognostic relationship of preoperative SIRI in high-grade gliomas and established a nomogram accordingly.

Methods

Data of operable high-grade glioma patients were analyzed. Kaplan-Meier, log-rank test, cox regression and propensity score matching (PSM) analysis were used to analyze survival. ROC curve and area under the curve (AUC) were used to compare the ability of preoperative SIRI, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) to predict prognosis. A nomogram based on the results was established. The consistency index (C-index) was calculated and a calibration curve was drawn.The prediction effect of the nomogram and WHO grade was compared by AUC.

Results

A total of 105 patients were included. Kaplan-Meier survival analysis showed that the overall survival (OS) of grade III gliomas patients with lower preoperative SIRI (SIRI<1.26) was significantly prolonged (p=0.037), and grade IV gliomas patients with lower preoperative SIRI had a tendency to obtain longer OS (p = 0.107). Cox regression showed preoperative SIRI was an independent prognostic factor for grade IV and grade III glioma, however, in IDH mutant-type IV gliomas, patients with lower SIRI only showed a tendency to obtain better OS. Similar results were obtained in PSM. The prognostic value of SIRI were better than PLR and MLR by ROC analysis. And in grade IV gliomas, the predictive value of SIRI was better than NLR. The nomogram established based on preoperative SIRI, age, extent of resection, number of gliomas, MGMT methylation status and histological types (only in grade III gliomas) could predict the prognosis more accurately.

Conclusion

SIRI was valuable for prognosis prediction in high-grade glioma. The nomogram covering SIRI could more accurately predict the survival rate in operable high-grade glioma patients.
Prenatal IgE as a Risk Factor for the Development of Childhood Neurodevelopmental Disorders
Authors: Straughen Jennifer K. , Sitarik Alexandra R. , Johnson Christine Cole , Wegienka Ganesa , Ownby Dennis R. , Johnson-Hooper Tisa M. , Allo Ghassan , Levin Albert M. , Cassidy-Bushrow Andrea E.
Published: May 2021

Background: Few studies have examined if maternal allergic disease is associated with an offspring's neurodevelopment. We hypothesized that Th-2 biased maternal immune function assessed as total serum immunoglobulin (Ig) E is associated with attention deficit hyperactivity disorder (ADHD).

Methods: Data are from the Wayne County Health, Environment, Allergy, and Asthma Longitudinal Study (WHEALS), a racially and socioeconomically diverse birth cohort in metropolitan Detroit, Michigan. Maternal total IgE was measured prenatally and at 1-month postpartum. Child total IgE was assessed at birth, 6 months, and 2 years of age. ADHD diagnosis was based on the parental report at the 10–12-year study visits or medical chart abstraction. Total IgE was log2 transformed. Poisson regression models with robust error variance were used to calculate the risk ratios (RR). Inverse probability weighting was used to correct for potential bias due to a loss to follow-up and non-response.

Results: Of the 636 maternal-child pairs in the analysis, 513 children were neurotypical and 123 had ADHD. Maternal prenatal total IgE was significantly associated with ADHD even after adjustment for potential confounders (RR = 1.08, 95% CI 1.03–1.13). Maternal and child IgE measures were positively and significantly correlated, but child total IgE was not associated with ADHD at any time point.

Conclusions: Maternal prenatal IgE may influence neurodevelopment, but additional studies are needed to confirm and expand these findings.
Case Report: Lessons Learned From Aortic Valve Rupture After Blunt Chest Trauma
Authors: Zhao Qu-ming , Lai Ling-yu , He Lan , Liu Fang
Published: May 2021

Aortic valve rupture (AVR) due to blunt chest trauma is extremely rare in the pediatric population, and little attention has been paid to such damages. Early diagnosis of AVR may not be easy in patients with multiple competing injuries and poor acoustic windows. We report a case of delayed diagnosis of AVR in a 12-year-old boy after falling from a height of 15 meters, who presented with recurrent hemoptysis and ventilator dependence. This rare case highlights the importance of performing transesophageal echocardiography in trauma patients when the images of transthoracic echocardiography are suboptimal, especially for those presenting with signs and symptoms suggestive of heart failure. The overall prognosis of aortic valve replacement is good.
Chronic Illness in Pediatric Critical Care
Authors: Murphy Salem Sinead , Graham Robert J.
Published: May 2021

Children and Youth with Special Healthcare Needs (CYSHCN), children with medical complexity (CMC), and children with chronic, critical illness (CCI) represent pediatric populations with varying degrees of medical dependance and vulnerability. These populations are heterogeneous in underlying conditions, congenital and acquired, as well as intensity of baseline medical needs. In times of intercurrent illness or perioperative management, these patients often require acute care services in the pediatric intensive care (PICU) setting. This review describes epidemiologic trends in chronic illness in the PICU setting, differentiates these populations from those without significant baseline medical requirements, reviews models of care designed to address the intersection of acute and chronic illness, and posits considerations for future roles of PICU providers to optimize the care and outcomes of these children and their families.
β-Caryophyllene, A Natural Dietary CB2 Receptor Selective Cannabinoid can be a Candidate to Target the Trinity of Infection, Immunity, and Inflammation in COVID-19
Authors: Jha Niraj Kumar , Sharma Charu , Hashiesh Hebaallah Mamdouh , Arunachalam Seenipandi , Meeran MF Nagoor , Javed Hayate , Patil Chandragouda R. , Goyal Sameer N. , Ojha Shreesh
Published: May 2021

Coronavirus disease (COVID-19), caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing pandemic and presents a public health emergency. It has affected millions of people and continues to affect more, despite tremendous social preventive measures. Identifying candidate drugs for the prevention and treatment of COVID-19 is crucial. The pathogenesis and the complications with advanced infection mainly involve an immune-inflammatory cascade. Therefore, therapeutic strategy relies on suppressing infectivity and inflammation, along with immune modulation. One of the most promising therapeutic targets for the modulation of immune-inflammatory responses is the endocannabinoid system, particularly the activation of cannabinoid type 2 receptors (CB2R), a G-protein coupled receptor which mediates the anti-inflammatory properties by modulating numerous signaling pathways. To pharmacologically activate the CB2 receptors, a naturally occurring cannabinoid ligand, beta-caryophyllene (BCP), received attention due to its potent anti-inflammatory, antiviral, and immunomodulatory properties. BCP is recognized as a full selective functional agonist on CB2 receptors and produces therapeutic effects by activating CB2 and the nuclear receptors, peroxisome proliferator-activated receptors (PPARs). BCP is regarded as the first dietary cannabinoid with abundant presence across cannabis and non-cannabis plants, including spices and other edible plants. BCP showed tissue protective properties and favorably modulates numerous signaling pathways and inhibits inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids. Based on its pharmacological properties, molecular mechanisms, and the therapeutic potential of BCP as an immunomodulator, anti-inflammatory, organ-protective, and antiviral, we hypothesize that BCP could be a promising therapeutic and/or preventive candidate to target the triad of infection, immunity, and inflammation in COVID-19. In line with numerous studies that proposed the potential of cannabinoids in COVID-19, BCP may be a novel candidate compound for pharmaceutical and nutraceutical development due to its unique functional receptor selectivity, wide availability and accessibility, dietary bioavailability, nonpsychoactivity, and negligible toxicity along with druggable properties, including favorable pharmacokinetic and physicochemical properties. Based on reasonable pharmacological mechanisms and therapeutic properties, we speculate that BCP has potential to be investigated against COVID-19 and will inspire further preclinical and clinical studies.
Comparing Predictions of a PBPK Model for Cyclosporine With Drug Levels From Therapeutic Drug Monitoring
Authors: Zapke Sonja E. , Willmann Stefan , Grebe Scott-Oliver , Menke Kristin , Thürmann Petra A. , Schmiedl Sven
Published: May 2021

This study compared simulations of a physiologically based pharmacokinetic (PBPK) model implemented for cyclosporine with drug levels from therapeutic drug monitoring to evaluate the predictive performance of a PBPK model in a clinical population. Based on a literature search model parameters were determined. After calibrating the model using the pharmacokinetic profiles of healthy volunteers, 356 cyclosporine trough levels of 32 renal transplant outpatients were predicted based on their biometric parameters. Model performance was assessed by calculating absolute and relative deviations of predicted and observed trough levels. The median absolute deviation was 6 ng/ml (interquartile range: 30 to 31 ng/ml, minimum = −379 ng/ml, maximum = 139 ng/ml). 86% of predicted cyclosporine trough levels deviated less than twofold from observed values. The high intra-individual variability of observed cyclosporine levels was not fully covered by the PBPK model. Perspectively, consideration of clinical and additional patient-related factors may improve the model’s performance. In summary, the current study has shown that PBPK modeling may offer valuable contributions for pharmacokinetic research in clinical drug therapy.
Broad Anti-Viral Capacities of Lian-Hua-Qing-Wen Capsule and Jin-Hua-Qing-Gan Granule and Rational use Against COVID-19 Based on Literature Mining
Authors: Shi Mingfei , Peng Bo , Li An , Li Ziyun , Song Ping , Li Jing , Xu Ruodan , Li Ning
Published: May 2021

The novel coronavirus disease 2019 (COVID-19) has become a matter of international concern as the disease is spreading exponentially. Statistics showed that infected patients in China who received combined treatment of Traditional Chinese Medicine and modern medicine exhibited lower fatality rate and relatively better clinical outcomes. Both Lian-Hua-Qing-Wen Capsule (LHQWC) and Jin-Hua-Qing-Gan Granule (JHQGG) have been recommended by China Food and Drug Administration for the treatment of COVID-19 and have played a vital role in the prevention of a variety of viral infections. Here, we desired to analyze the broad-spectrum anti-viral capacities of LHQWC and JHQGG, and to compare their pharmacological functions for rational clinical applications. Based on literature mining, we found that both LHQWC and JHQGG were endowed with multiple antiviral activities by both targeting viral life cycle and regulating host immune responses and inflammation. In addition, from literature analyzed, JHQGG is more potent in modulating viral life cycle, whereas LHQWC exhibits better efficacies in regulating host anti-viral responses. When translating into clinical applications, oral administration of LHQWC could be more beneficial for patients with insufficient immune functions or for patients with alleviated symptoms after treatment with JHQGG.
Evaluation of the Hypoglycemic Activity of Morchella conica by Targeting Protein Tyrosine Phosphatase 1B
Authors: Begum Naeema , Nasir Abdul , Parveen Zahida , Muhammad Taj , Ahmed Asma , Farman Saira , Jamila Nargis , Shah Mohib , Bibi Noor Shad , Khurshid Akif , Huma Zille , Khalil Atif Ali Khan , Albrakati Ashraf , Batiha Gaber El-Saber
Published: May 2021

Morchella conica (M. conica) Pers. is one of six wild edible mushrooms that are widely used by Asian and European countries for their nutritional value. The present study assessed the anti-diabetic potential of M. conica methanolic extract (100 mg/kg body weight) on streptozotocin (STZ)-induced diabetic mice. STZ was used in a single dose of 65 mg/kg to establish diabetic models. Body weights, water/food intake and fasting blood glucose levels were measured. Histopathological analysis of the pancreas and liver were performed to evaluate STZ-induced tissue injuries. In addition, in vitro assays such as α-amylase and protein tyrosine phosphatase 1B (PTP1B) inhibitory, antiglycation, antioxidant and cytotoxicity were performed. The in vitro study indicated potent PTP1B inhibitory potential of M. conica with an IC50 value of 26.5 μg/ml as compared to the positive control, oleanolic acid (IC50 36.2 μg/ml). In vivo investigation showed a gradual decrease in blood sugar level in M. conica-treated mice (132 mg/dl) at a concentration of 100 mg/kg as compared to diabetic mice (346 mg/dl). The extract positively improved liver and kidney damages as were shown by their serum glutamic pyruvic transaminase, serum glutamic oxaloacetate, alkaline phosphatase, serum creatinine and urea levels. Histopathological analysis revealed slight liver and pancreas improvement of mice treated with extract. Cytotoxicity assays displayed lower IC50 values. Based on the present results of the study, it may be inferred that M. conica are rich in bioactive compounds responsible for antidiabetic activity and this mushroom may be a potential source of antidiabetic drug. However, further studies are required in terms of isolation of bioactive compounds to validate the observed results.
Toward the Development of an On-Chip Acoustic Focusing Fluorescence Lifetime Flow Cytometer
Authors: Sambrano Jesus , Rodriguez Felicia , Martin John , Houston Jessica P.
Published: May 2021

Conventional flow cytometry is a valuable quantitative tool. Flow cytometers reveal physical and biochemical information from cells at a high throughput, which is quite valuable for many biomedical, biological, and diagnostic research fields. Flow cytometers range in complexity and typically provide multiparametric data for the user at rates of up to 50,000 cells measured per second. Cytometry systems are configured such that fluorescence or scattered light signals are collected per-cell, and the integrated optical signal at a given wavelength range indicates a particular cellular feature such as phenotype or morphology. When the timing of the optical signal is measured, the cytometry system becomes “time-resolved.” Time-resolved flow cytometry (TRFC) instruments can detect fluorescence decay kinetics, and such measurements are consequential for Förster Resonance Energy Transfer (FRET) studies, multiplexing, and metabolic mapping, to name a few. TRFC systems capture fluorescence lifetimes at rates of thousands of cells per-second, however the approach is challenged at this throughput by terminal cellular velocities. High flow rates limit the total number of photons integrated per-cell, reducing the reliability of the average lifetime as a cytometric parameter. In this contribution, we examine an innovative approach to address this signal-to-noise issue. The technology merges time-resolved hardware with microfluidics and acoustics. We present an “acoustofluidic” time-resolved flow cytometer so that cellular velocities can be adjusted on the fly with a standing acoustic wave (SAW). Our work shows that acoustic control can be combined with time-resolved features to appropriately balance the throughput with the optical signals necessary for lifetime data.
Motor Unit Force Potentiation and Calcium Handling Protein Concentration in Rat Fast Muscle After Resistance Training
Authors: Łochyński Dawid , Kaczmarek Dominik , Grześkowiak Marcin , Majerczak Joanna , Podgórski Tomasz , Celichowski Jan
Published: May 2021

Post-tetanic potentiation (PTP) of force depends on intramuscular Ca2+levels and sensitivity and may be affected by fatigue. The aim of this study was to determine the ability of isolated fast fatigue-resistant (FR) and fast-fatigable (FF) motor units (MUs) to potentiate force evoked with single and 40-Hz electrical stimulation after 5 weeks of voluntary weight-lifting training. Tetanic contractions evoked by gradually increasing (10–150 Hz) stimulation frequency served as conditioning stimulation. Additionally, the concentration of myosin light chain kinase and proteins engaged in calcium handling was measured in rat fast medial gastrocnemius muscle. After the training, the potentiation of twitch force and peak rate of force development was increased in FF but not FR MUs. Force potentiation of 40-Hz tetanic contractions was increased in both fast MU types. After the training, the twitch duration of FR MUs was decreased, and FF MUs were less prone to high-frequency fatigue during conditioning stimulation. Muscle concentration of triadin was increased, whereas concentrations of ryanodine receptor 1, junctin, FKBP12, sarcoplasmic reticulum calcium ATPase 1, parvalbumin, myosin light chain kinase, and actomyosin adenosine triphosphatase content were not modified. After short-term resistance training, the twitch contraction time and twitch:tetanus force ratio of FR MUs are decreased, and PTP ability is not changed. However, PTP capacity is increased in response to submaximal activation. In FF MUs increase in PTP ability coexists with lesser fatigability. Further work is required to find out if the increase in triadin concentration has any impact on the observed contractile response.
Genome-Wide Association Study for Grain Micronutrient Concentrations in Wheat Advanced Lines Derived From Wild Emmer
Authors: Liu Jia , Huang Lin , Li Tingxuan , Liu Yaxi , Yan Zehong , Tang Guan , Zheng Youliang , Liu Dengcai , Wu Bihua
Published: May 2021

Wheat is one of the important staple crops as the resources of both food and micronutrient for most people of the world. However, the levels of micronutrients (especially Fe and Zn) in common wheat are inherently low. Biofortification is an effective way to increase the micronutrient concentration of wheat. Wild emmer wheat (Triticum turgidum ssp. dicoccoides, AABB, 2n = 4x = 28) is an important germplasm resource for wheat micronutrients improvement. In the present study, a genome-wide association study (GWAS) was performed to characterize grain iron, zinc, and manganese concentration (GFeC, GZnC, and GMnC) in 161 advanced lines derived from wild emmer. Using both the general linear model and mixed linear model, we identified 14 high-confidence significant marker-trait associations (MTAs) that were associated with GFeC, GZnC, and GMnC of which nine MTAs were novel. Six MTAs distributed on chromosomes 3B, 4A, 4B, 5A, and 7B were significantly associated with GFeC. Three MTAs on 1A and 2A were significantly associated with GZnC and five MTAs on 1B were significantly associated with GMnC. These MTAs show no negative effects on thousand kernel weight (TKW), implying the potential value for simultaneous improvement of micronutrient concentrations and TKW in breeding. Meanwhile, the GFeC, GZnC and GMnC are positively correlated, suggesting that these traits could be simultaneously improved. Genotypes containing high-confidence MTAs and 61 top genotypes with a higher concentration of grain micronutrients were recommended for wheat biofortification breeding. A total of 38 candidate genes related to micronutrient concentrations were identified. These candidates can be classified into four main groups: enzymes, transporter proteins, MYB transcription factor, and plant defense responses proteins. The MTAs and associated candidate genes provide essential information for wheat biofortification breeding through marker-assisted selection (MAS).
Characterization of BoaCRTISO Reveals Its Role in Carotenoid Biosynthesis in Chinese Kale
Authors: Jiang Min , Zhang Fen , Yuan Qiao , Lin Peixing , Zheng Hao , Liang Sha , Jian Yue , Miao Huiying , Li Huanxiu , Wang Qiaomei , Sun Bo
Published: May 2021

Carotenoids are organic pigments that play an important role in both plant coloration and human health; they are a critical subject in molecular breeding due to growing demand for natural molecules in both food and medicine. In this study, we focus upon characterizing BoaCRTISO, the carotenoid isomerase gene before the branch of the carotenoid biosynthetic pathway, which is expressed in all organs and developmental stages of Chinese kale, and BoaCRTISO, which is located in the chloroplast. The expression of BoaCRTISO is induced by strong light, red and blue combined light, and gibberellic acid treatment, but it is suppressed by darkness and abscisic acid treatment. We obtained BoaCRTISO-silenced plants via virus-induced gene silencing technology, and the silence efficiencies ranged from 52 to 77%. The expressions of most carotenoid and chlorophyll biosynthetic genes in BoaCRTISO-silenced plants were downregulated, and the contents of carotenoids and chlorophyll were reduced. Meanwhile, BoaCRTISO-silenced plants exhibited phenotypes of yellowing leaves and inhibited growth. This functional characterization of BoaCRTISO provides insight for the biosynthesis and regulation of carotenoid in Chinese kale.
Development, Identification, and Application of a Germplasm Specific SCAR Marker for Dendrobium officinale Kimura et Migo
Authors: Zheng Kaixin , Cai Yuchen , Chen Weijie , Gao Yadi , Jin Jingjing , Wang Huizhong , Feng Shangguo , Lu Jiangjie
Published: May 2021

The stems of Dendrobium officinale have been used as a rare and valuable Chinese tonic medicine, known as “Tiepi Fengdou”, since the Qing dynasty. Because of the increased market demand and continued exploitation of this plant, the reserves of wild D. officinale resources have been depleted, and D. officinale products on the market are being increasingly adulterated. Such changes have strongly affected the sustainable utilization of this valuable medicinal plant resource and the development of related industries. In this study, a species-specific DNA marker was developed for the rapid and accurate authentication of D. officinale. In total, 36 start codon-targeted (SCoT) polymorphism primers were screened in 36 definite Dendrobium species, and a distinct species-specific DNA amplicon (SCoT13-215) for D. officinale was obtained. After the sequence was cloned and sequenced, a sequence-characterized amplified region marker was developed (named SHF/SHR) and validated through PCR amplification of all 38 Dendrobium samples. The marker’s specificity for D. officinale was confirmed through the consistent amplification of a clear 197-bp band. This SCAR marker can be used to rapidly, effectively, and reliably identify D. officinale among various Dendrobium species and may play an important role in ensuring the quality of medicinal preparations and protecting the germplasm of this important medicinal species.
Individual Differences in the Association Between Celebrity Worship and Subjective Well-Being: The Moderating Role of Gender and Age
Authors: Zsila Ágnes , Orosz Gábor , McCutcheon Lynn E. , Demetrovics Zsolt
Published: May 2021

The association of celebrity worship with mental health concerns has been extensively studied in the past two decades. However, there is a lack of research on basic demographic characteristics that can potentially alter the link between celebrity admiration and different aspects of mental health. The present study investigates the possible moderating role of gender, age, and opposite/same-gender celebrity selection on the association of celebrity worship with general well-being, self-esteem and perceived daytime sleepiness. A total of 1763 Hungarian adults (66.42% men, Mage = 37.2 years, SD = 11.4) completed an online survey focusing on attitudes and behaviors relating to celebrities and mental well-being. The moderation analysis showed that (i) the negative association between celebrity worship and self-esteem was slightly stronger for women than for men, and (ii) the association between celebrity worship and perceived daytime sleepiness was slightly stronger for younger individuals than for older ones. Although both gender and age were particularly weak moderators, these results draw the attention to some potential individual differences when interpreting links between celebrity worship and different aspects of mental health.
Think Unique: Perceptions of Uniqueness Increases Resistance to Persuasion and Attitude-Intention Relations
Authors: Blankenship Kevin L. , Kane Kelly A. , Machacek Marielle G.
Published: May 2021

The present research examines whether the perceived uniqueness of one’s thoughts and salience of uniqueness motivations can influence attitude strength and resistance. Participants who rated their thoughts as relatively unique formed attitudes that showed greater correspondence with behavioral intentions to act on the attitude (Study 1). In Study 2, participants who recalled a previous purchase motivated by the desire to be unique (versus to fit in) after generating message counterarguments were less persuaded (more resistant) and reported greater willingness to act on their (negative) attitude. Moreover, attitudes mediated the effect of the purchase manipulation on intentions to act on the attitude.
When to Scaffold Motivational Self-Regulation Strategies for High School Students' Science Text Comprehension
Authors: Michalsky Tova
Published: May 2021

Noting the important role of motivation in science students' reading comprehension, this 14-weeks quasi-experiment investigated the optimal timing for implementation of metamotivational scaffolding for self-regulation of scientific text comprehension. The “IMPROVE” metamotivational self-regulatory model (Introducing new concepts, Metamotivation questioning, Practicing, Reviewing and reducing difficulties, Obtaining mastery, Verification, and Enrichment) was embedded at three different phases of secondary students' engagement with scientific texts and exercises (before, during, or after) to examine effects of timing on groups' science literacy and motivational regulation. Israeli 10th graders (N = 202) in eight science classrooms received the same scientific texts and reading comprehension exercises in four groups. Three treatment groups received metamotivational scaffolding before (n = 52), during (n = 50), or after text engagement (n = 54). The control group (n = 46) received standard instructional methods with no metamotivational scaffolding. Pretests and posttests assessed science literacy, domain-specific microbiology knowledge, and metamotivation regulation. Intergroup differences were non-significant at pretest but significant at posttest. The “before” group significantly outperformed all other groups. The “after” group significantly outperformed the “during” group, and the control group scored lowest. Outcomes suggested delivery of metamotivational scaffolding as a potentially important means for promoting students' science literacy and effortful perseverance with challenging science tasks, especially at the reflection-before-action stage for looking ahead and also at the reflection-on-action stage for looking back. More theoretical and practical implications of this preliminary study were discussed to meet the growing challenges in science teaching schoolwork.
Battling for Consumer's Positive Purchase Intention: A Comparative Study Between Two Psychological Techniques to Achieve Success and Sustainability for Digital Entrepreneurships
Authors: Dong Dandan , Malik Haider Ali , Liu Yaoping , Elashkar Elsayed Elsherbini , Shoukry Alaa Mohamd , Khader J. A.
Published: May 2021

This research focuses on students' online purchase intentions in Pakistan toward different products available for sale on numerous e-business websites. This study's main objective is to determine which methodology is better to enhance customer online purchase intention. It also aims to discover how to improve perceived benefits and lower perceived risks associated with any available online product and entrepreneurship. AMOS 24 has been used to deal with the mediation in study design with bootstrap methodology. The study was conducted on 250 students from different educational institutes in Pakistan using a simple random sampling technique. A finding of this study suggests that both methods positively impact online purchase intention of consumers and sustainable digital economy. But social media advertisement is more effective through enhancing the perceived benefits of products. In contrast, product content factors are more effective at lowering the perceived risks associated with available online products.