bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Post-stroke Cognition: In-hospital Predictors and the Association With Functional Outcome
Authors: Sharma Richa , Mallick Dania , Llinas Rafael H. , Marsh Elisabeth B.
Published: December 2020

Purpose: To characterize and predict early post-stroke cognitive impairment by describing cognitive changes in stroke patients 4–8 weeks post-infarct, determining the relationship between cognitive ability and functional status at this early time point, and identifying the in-hospital risk factors associated with early dysfunction.

Materials and Methods: Data were collected for 214 patients with ischemic stroke and 39 non-stroke controls. Montreal Cognitive Assessment (MoCA) exams were administered at post-hospitalization clinic visits approximately 4–8 weeks after infarct. MoCA scores were compared for patients with: no stroke, minor stroke [NIH Stroke Scale (NIHSS) < 5], and major stroke. Ordinal logistic regression was performed to assess the relationship between MoCA score and functional status [modified Rankin Scale score (mRS)] at follow-up. Predictors of MoCA < 26 and < 19 (cutoffs for mild and severe cognitive impairment, respectively) at follow-up were identified by multivariable logistic regression using variables available during hospitalization.

Results: Post stroke cognitive impairment was common, with 66.8% of patients scoring < 26 on the MoCA and 22.9% < 19. The average total MoCA score at follow-up was 18.7 (SD 7.0) among major strokes, 23.6 (SD 4.8) among minor strokes, and 27.2 (SD 13.0) among non-strokes (p = <0.0001). The follow-up MoCA score was associated with the follow-up mRS in adjusted analysis (OR 0.69; 95% C.I. 0.59–0.82). Among patients with no prior cognitive impairment (N = 201), a lack of pre-stroke employment, admission NIHSS > 6, and left-sided infarct predicted a follow-up MoCA < 26 (c-statistic 0.75); while admission NIHSS > 6 and infarct volume > 17 cc predicted a MoCA < 19 (c-statistic 0.75) at follow-up.

Conclusion: Many patients experience early post-stroke cognitive dysfunction that significantly impacts function during a critical time period for decision-making regarding return to work and future independence. Dysfunction measured at 4–8 weeks can be predicted during the inpatient hospitalization. These high-risk individuals should be identified for targeted rehabilitation and counseling to improve longer-term post-stroke outcomes.
Involvement of the Right Dorsolateral Prefrontal Cortex in Numerical Rule Induction: A Transcranial Direct Current Stimulation Study
Authors: Yao Yuzhao , Jia Xiuqin , Luo Jun , Chen Feiyan , Liang Peipeng
Published: December 2020

Numerical inductive reasoning has been considered as one of the most important higher cognitive functions of the human brain. Importantly, previous behavioral studies have consistently reported that one critical component of numerical inductive reasoning is checking, which often occurs when a discrepant element is discovered, and reprocessing is needed to determine whether the discrepancy is an error of the original series. However, less is known about the neural mechanism underlying the checking process. Given that the checking effect involves cognitive control processes, such as the incongruent resolution, that are linked to the right dorsolateral prefrontal cortex (DLPFC), this study hypothesizes that the right DLPFC may play a specific role in the checking process. To test the hypothesis, this study utilized the transcranial direct current stimulation (tDCS), a non-invasive brain stimulation method that could modulate cortical excitability, and examined whether and how the stimulation of the right DLPFC via tDCS could modulate the checking effect during a number-series completion problem task. Ninety healthy participants were allocated to one of the anodal, cathodal, and sham groups. Subjects were required to verify whether number sequences formed rule-based series, and checking effect was assessed by the difference in performance between invalid and valid conditions. It was found that significantly longer response times (RTs) were exhibited in invalid condition compared with valid condition in groups of anodal, cathodal, and sham tDCS. Furthermore, the anodal tDCS significantly shortened the checking effect than those of the cathodal and sham groups, whereas no significantly prolonged checking effect was detected in the cathodal group. The current findings indicated that anodal tDCS affected the process of checking, which suggested that the right DLPFC might play a critical role in the checking process of numerical inductive reasoning by inhibiting incongruent response.
Repeated Contrast Adaptation Does Not Cause Habituation of the Adapter
Authors: Dong Xue , Du Xinxin , Bao Min
Published: December 2020

Adaptation can optimize information processing by allowing the visual system to always adjust to the environment. However, only a few studies have investigated how the visual system makes adjustments to repeatedly occurring changes in the input, still less about the related neural mechanism. Our previous study found that contrast adaptation attenuated after multiple daily sessions of repeated adaptation, which was explained by the habituation of either the adapter’s effective strength or the adaptation mechanisms. To examine the former hypothesis, in the present study we used the frequency tagging technique to measure the adapter-elicited steady-state visual evoked potential (SSVEP) amplitudes. Participants repeatedly adapted to the same contrast adapter in a top-up manner for six continuous days, which was called training of adaptation. The behavioral adaptation effect and SSVEP response to the trained adapter and an untrained control adapter were measured before and after training. The psychophysical results showed that the effect of adaptation in the trained condition significantly reduced after training, replicating our previous finding. Contradicting the prediction of the hypothesis that repeated adaptation attenuated the effective strength of the adapter, the SSVEP amplitude was unchanged after training, which was further confirmed by an equivalence test. Taken together, the results challenge the account of habituation of adapter in repeated adaptation, while leaving the account of habituation of adaptation mechanism to be tested.
Comparative Analysis of Dorsal Root, Nodose and Sympathetic Ganglia for the Development of New Analgesics
Authors: Sapio Matthew R. , Vazquez Fernando A. , Loydpierson Amelia J. , Maric Dragan , Kim Jenny J. , LaPaglia Danielle M. , Puhl Henry L. , Lu Van B. , Ikeda Stephen R. , Mannes Andrew J. , Iadarola Michael J.
Published: December 2020

Interoceptive and exteroceptive signals, and the corresponding coordinated control of internal organs and sensory functions, including pain, are received and orchestrated by multiple neurons within the peripheral, central and autonomic nervous systems. A central aim of the present report is to obtain a molecularly informed basis for analgesic drug development aimed at peripheral rather than central targets. We compare three key peripheral ganglia: nodose, sympathetic (superior cervical), and dorsal root ganglia in the rat, and focus on their molecular composition using next-gen RNA-Seq, as well as their neuroanatomy using immunocytochemistry and in situ hybridization. We obtained quantitative and anatomical assessments of transmitters, receptors, enzymes and signaling pathways mediating ganglion-specific functions. Distinct ganglionic patterns of expression were observed spanning ion channels, neurotransmitters, neuropeptides, G-protein coupled receptors (GPCRs), transporters, and biosynthetic enzymes. The relationship between ganglionic transcript levels and the corresponding protein was examined using immunohistochemistry for select, highly expressed, ganglion-specific genes. Transcriptomic analyses of spinal dorsal horn and intermediolateral cell column (IML), which form the termination of primary afferent neurons and the origin of preganglionic innervation to the SCG, respectively, disclosed pre- and post-ganglionic molecular-level circuits. These multimodal investigations provide insight into autonomic regulation, nodose transcripts related to pain and satiety, and DRG-spinal cord and IML-SCG communication. Multiple neurobiological and pharmacological contexts can be addressed, such as discriminating drug targets and predicting potential side effects, in analgesic drug development efforts directed at the peripheral nervous system.
Recent Developments in Data Independent Acquisition (DIA) Mass Spectrometry: Application of Quantitative Analysis of the Brain Proteome
Authors: Li Ka Wan , Gonzalez-Lozano Miguel A. , Koopmans Frank , Smit August B.
Published: December 2020

Mass spectrometry is the driving force behind current brain proteome analysis. In a typical proteomics approach, a protein isolate is digested into tryptic peptides and then analyzed by liquid chromatography–mass spectrometry. The recent advancements in data independent acquisition (DIA) mass spectrometry provide higher sensitivity and protein coverage than the classic data dependent acquisition. DIA cycles through a pre-defined set of peptide precursor isolation windows stepping through 400–1,200 m/z across the whole liquid chromatography gradient. All peptides within an isolation window are fragmented simultaneously and detected by tandem mass spectrometry. Peptides are identified by matching the ion peaks in a mass spectrum to a spectral library that contains information of the peptide fragment ions' pattern and its chromatography elution time. Currently, there are several reports on DIA in brain research, in particular the quantitative analysis of cellular and synaptic proteomes to reveal the spatial and/or temporal changes of proteins that underlie neuronal plasticity and disease mechanisms. Protocols in DIA are continuously improving in both acquisition and data analysis. The depth of analysis is currently approaching proteome-wide coverage, while maintaining high reproducibility in a stable and standardisable MS environment. DIA can be positioned as the method of choice for routine proteome analysis in basic brain research and clinical applications.
Associations Between Added Sugar Intake and Risk of Four Different Cardiovascular Diseases in a Swedish Population-Based Prospective Cohort Study
Authors: Janzi Suzanne , Ramne Stina , González-Padilla Esther , Johnson Linda , Sonestedt Emily
Published: December 2020

Aims: Although diet is one of the main modifiable risk factors of cardiovascular disease, few studies have investigated the association between added sugar intake and cardiovascular disease risk. This study aims to investigate the associations between intake of total added sugar, different sugar-sweetened foods and beverages, and the risks of stroke, coronary events, atrial fibrillation and aortic stenosis.

Methods: The study population consists of 25,877 individuals from the Malmö Diet and Cancer Study, a Swedish population-based prospective cohort. Dietary data were collected using a modified diet history method. National registers were used for outcome ascertainment.

Results: During the mean follow-up of 19.5 years, there were 2,580 stroke cases, 2,840 coronary events, 4,241 atrial fibrillation cases, and 669 aortic stenosis cases. Added sugar intakes above 20 energy percentage were associated with increased risk of coronary events compared to the lowest intake category (HR: 1.39; 95% CI: 1.09–1.78), and increased stroke risk compared to intakes between 7.5 and 10 energy percentage (HR: 1.31; 95% CI: 1.03 and 1.66). Subjects in the lowest intake group for added sugar had the highest risk of atrial fibrillation and aortic stenosis. More than 8 servings/week of sugar-sweetened beverages were associated with increased stroke risk, while ≤2 servings/week of treats were associated with the highest risks of stroke, coronary events and atrial fibrillation.

Conclusion: The results indicate that the associations between different added sugar sources and cardiovascular diseases vary. These findings emphasize the complexity of the studied associations and the importance of considering different added sugar sources when investigating health outcomes.
Metabolic and Gut Microbiota Responses to Sourdough Pasta Consumption in Overweight and Obese Adults
Authors: Shah Shrushti , Brown Paul D. S. , Mayengbam Shyamchand , Gänzle Michael G. , Wang Weilan , Mu Chunlong , Lettrari Silvio , Bertagnolli Craig , Shearer Jane
Published: December 2020

Increasing consumer interest in fermented products has driven the emergence of a number of novel foods including shelf-stable sourdough pasta. This study comprehensively examined the impact of fermentation on the microbial composition of the culture, pasta, its subsequent effects on glycemic responses and gut microbiota in overweight men and women (>25 kg/m2) compared to a conventional, non-fermented pasta. Two, randomized crossover trials were performed. Study A examined acute feeding responses to each product wherein fasted participants completed a meal tolerance test comprised of 75 g of conventional or sourdough pasta to examine glycemic responses. Results showed enhanced gastric emptying with sourdough, but no difference in overall blood glucose, insulin or satiety hormone responses between the treatments. Study B consisted of three standard oral glucose tolerance tests as well as fecal collection for sequencing at baseline and following each pasta intervention (150 g or 2 serving/d for 5 days) followed by a 2-week washout period. Results showed no differential impact of either pasta treatment on glucose tolerance. Analysis of fecal bacterial and fungal (mycobiome) microbiota showed no change at the individual species or genus levels. However, fungi were adaptive following chronic pasta consumption with decreases in alpha diversity of fungi following sourdough, but not conventional pasta. This was accompanied by reductions in total fecal short chain fatty acid concentrations. In conclusion, sourdough fermentation did not change the overall glycemic properties of the pasta, incretin responses or bacterial gut microbiota, but appears to impact microbiome fungal community structure with chronic consumption.
Case Report: Prostate Adenocarcinoma With Mucinous Features of Normal-Level Serum PSA, Atypical Imaging, Biopsy-Negative, and Peculiar Urethrocystoscopic Manifestation
Authors: Zhang Yao , Shen Hua , Liao Kai , Wu Weili , Li Jiuming , Yu Hongbo , Wu Hongfei , Wang Zengjun
Published: December 2020

Background

Mucinous tumors of the prostate are seen as rare morphological variants of prostate carcinoma. Misdiagnosis and missed diagnosis are frequent clinically, especially when the clinical performance appears atypical. Furthermore, there has not been reported about the urethrocystoscopic performance of mucinous adenocarcinoma growing into the prostatic urethra so far.

Case Presentation

The current case report describes a 48-year old Asian male who was hospitalized because of intermittent gross hematuria for more than two months. The patient was diagnosed as prostatic space occupying lesions and an examination of needle biopsy was conducted on him, which did not indicate a definite malignancy. Transurethral plasma kinetic resection of the prostate (TUPKP) was performed for the patient, but the postoperative pathology revealed prostatic adenocarcinoma with mucinous features. Specifically, two cord-like neoplasms, extending to the bladder neck, were found through urethrocystoscopy in the prostatic urethra, both of which grew pedicles. The pedicles were situated on the right side of the parenchyma of the prostate. Finally, the patient underwent radical prostatectomy three weeks later.

Conclusion

Here, we reported a case that prostatic adenocarcinoma with mucinous features was diagnosed after TUPKP. The patient had normal serum prostate-specific antigen levels with atypical images and negative biopsy result. This report lays stress on the vigilance of clinicians in prostate mucinous adenocarcinoma and makes a description of its peculiar urethrocystoscopic manifestation, typical imaging, and unique growth pattern for the first time.
The Esophageal Adenocarcinoma Epidemic Has Reached Hungary: A Multicenter, Cross-Sectional Study
Authors: Tinusz Benedek , Szapáry László Botond , Paládi Bence , Papp András , Bogner Barna , Hegedűs Ivett , Bellyei Szabolcs , Vincze Áron , Solt Jenő , Micsik Tamás , Dunás-Varga Veronika , Pályu Eszter , Vass Tamás , Schnabel Tamás , Farkas Nelli , Hegyi Péter , Thrift Aaron P. , Erőss Bálint
Published: December 2020

Background

The epidemiology of esophageal cancer has changed dramatically over the past 4 decades in many Western populations. We aimed to understand the Hungarian epidemiologic trends of esophageal squamous cell cancer (SCC) and adenocarcinoma (AC).

Methods

We performed a cross-sectional study using data from esophageal cancer patients diagnosed between 1992 and 2018 at eight tertiary referral centers in four major cities of Hungary. We retrospectively identified cases in the electronic databases of each center and collected data on gender, age at diagnosis, year of diagnosis, specialty of the origin center, histological type, and localization of the tumor. Patients were grouped based on the two main histological types: AC or SCC. For statistical analysis, we used linear regression models, chi-square tests, and independent sample t tests.

Results

We extracted data on 3,283 patients with esophageal cancer. Of these, 2,632 were diagnosed with either of the two main histological types; 737 had AC and 1,895 SCC. There was no significant difference in the gender ratio of the patients between AC and SCC (80.1 vs 81.8% males, respectively; p = 0.261). The relative incidence of AC increased over the years (p < 0.001, b = 1.19 CI: 0.84–1.54). AC patients were older at diagnosis than SCC patients (64.37 ± 11.59 vs 60.30 ± 10.07 years, p < 0.001). The age of patients at the diagnosis of primary esophageal cancer increased over time (p < 0.001, R = 0.119).

Conclusions

The rapid increase in the relative incidence of AC and simultaneous decrease of the relative incidence of SCC suggest that this well-established Western phenomenon is also present in Hungary.
Ex Vivo Fluorescein-Assisted Confocal Laser Endomicroscopy (CONVIVO® System) in Patients With Glioblastoma: Results From a Prospective Study
Authors: Acerbi Francesco , Pollo Bianca , De Laurentis Camilla , Restelli Francesco , Falco Jacopo , Vetrano Ignazio G. , Broggi Morgan , Schiariti Marco , Tramacere Irene , Ferroli Paolo , DiMeco Francesco
Published: December 2020

Background

Confocal laser endomicroscopy (CLE) allowing intraoperative near real-time high-resolution cellular visualization is a promising method in neurosurgery. We prospectively tested the accuracy of a new-designed miniatured CLE (CONVIVO® system) in giving an intraoperative first-diagnosis during glioblastoma removal.

Methods

Between January and May 2018, 15 patients with newly diagnosed glioblastoma underwent fluorescein-guided surgery. Two biopsies from both tumor central core and margins were harvested, dividing each sample into two specimens. Biopsies were firstly intraoperatively ex vivo analyzed by CLE, subsequently processed for frozen and permanent fixation, respectively. Then, a blind comparison was conducted between CLE and standard permanent section analyses, checking for CLE ability to provide diagnosis and categorize morphological patterns intraoperatively.

Results

Blindly comparing CONVIVO® and frozen sections images we obtained a high rate of concordance in both providing a correct diagnosis and categorizing patterns at tumor central core (80 and 93.3%, respectively) and at tumor margins (80% for both objectives). Comparing CONVIVO® and permanent sections, concordance resulted similar at central core (total/partial concordance in 80 and 86.7% for diagnosis and morphological categorization, respectively) and lower at tumor margins (66.6% for both categories). Time from fluorescein injection and time from biopsy sampling to CONVIVO® scanning was 134 ± 31 min (122–214 min) and 9.23 min (1–17min), respectively. Mean time needed for CONVIVO® images interpretation was 5.74 min (1–7 min).

Conclusions

The high rate of diagnostic/morphological consistency found between CONVIVO® and frozen section analyses suggests the possibility to use CLE as a complementary tool for intraoperative diagnosis of ex vivo tissue specimens during glioblastoma surgery.
Primary Brain Tumor Research Productivity in Southeast Asia and Its Association With Socioeconomic Determinants and Burden of Disease
Authors: Mondia Mark Willy L. , Espiritu Adrian I. , Jamora Roland Dominic G.
Published: December 2020

Background

There is an unmet need to assess research productivity from southeast Asia (SEA) regarding primary central nervous system (CNS) tumors. The country’s economy, landscape of neurology practice, and disease burden are hypothesized to correlate with scientific output. This study aimed to objectively measure the impact of published studies on primary brain tumors in SEA and to assess for correlation with socioeconomic determinants and burden of disease.

Methods

We systematically searched electronic databases for relevant articles from SEA on primary CNS tumor until July 31, 2020. Bibliometric indices were reported and subjected to correlational analysis with population size, gross domestic product (GDP) per capita, percentage (%) GDP for research and development (R&D), total number of neurologists, disease incidence, deaths, and disability-adjusted life years.

Results

A total of 549 articles were included, consisting primarily of case reports (n=187, 34.06%) and discussed gliomas (n=195, 35.52%). Singapore published the most number of the articles (n=246, 44.8%). Statistical analysis showed a positive correlation between %GDP for R&D and total publication. Additionally, negative relationships were noted between burden of disease and total neurologist with most bibliometric indices. However, GDP per capita was not correlated with measures for research productivity.

Conclusion

The low impact of scientific output on primary CNS tumors in SEA does not address the growing epidemiology and burden of this disease. An increase in the GDP growth and financial and manpower investment to R&D may significantly improve research productivity in SEA.
Circulating Chromogranin A Is Cleaved Into Vasoregulatory Fragments in Patients With Pancreatic Ductal Adenocarcinoma
Authors: Reni Michele , Andreasi Valentina , Gasparri Anna Maria , Dugnani Erica , Colombo Barbara , Macchini Marina , Bianco Mimma , Dallatomasina Alice , Citro Antonio , Assi Emma , Protti Maria Pia , Esposito Antonio , Falconi Massimo , Curnis Flavio , Piemonti Lorenzo , Corti Angelo
Published: December 2020

Chromogranin A (CgA), a secretory protein released in the blood by the neuroendocrine system, consists of a mixture of full-length molecules and fragments endowed of vasoregulatory activity. The extent and the role of CgA fragmentation were investigated in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC, n=172). Multivariate analysis showed that full-length CgA was associated with better progression free and overall survival, whereas CgA C-terminal fragmentation was associated with worse prognosis. In vitro studies showed that PDAC cells can promote the cleavage of CgA C-terminal region by activating plasminogen to plasmin. Limited digestion of full-length CgA with plasmin abolished its anti-angiogenic activity and generated pro-angiogenic molecules. The fragmentation of CgA C-terminal region was increased also in murine models of PDAC. In these models, the inhibition of CgA fragmentation with aprotinin, an inhibitor of plasmin and other serine proteases, or the blockade of pro-angiogenic fragments with specific antibodies inhibited the growth of PDAC implanted subcutaneously in mice. Finally, administration of full-length CgA to mice bearing orthotopic PDAC reduced tumor perfusion, as measured by contrast-enhanced ultrasound. These findings suggest that PDAC can promote the cleavage of circulating CgA C-terminal region to generate fragments that regulate the tumor vascular biology and that may represent new potential therapeutic targets.
The Roles of Beclin 1 Expression in Gastric Cancer: A Marker for Carcinogenesis, Aggressive Behaviors and Favorable Prognosis, and a Target of Gene Therapy
Authors: Zheng Hua-chuan , Zhao Shuang , Xue Hang , Zhao En-hong , Jiang Hua-mao , Hao Chang-lai
Published: December 2020

Beclin 1 is encoded by Becn1, and plays a role in tumorigenesis, neurodegeneration, apoptosis and autophagy. Here, the aggressive phenotypes and relevant proteins were examined after Beclin 1 expression was altered in gastric cancer cells. We also observed the effects of Beclin 1 on gastric carcinogenesis using Becn1 knockout mice. Finally, clinicopathological significances of Beclin 1 expression were analyzed using meta- and bioinformatics analyses. Becn1 overexpression was found to inhibit proliferation, glucose metabolism, migration and invasion of gastric cancer cells, whereas its knockdown caused the opposite effects. Beclin 1 suppressed the tumor growth by decreasing proliferation and increasing apoptosis. The heterozygous abrogation of Becn1 in gastric pit, parietal and chief cells could not cause any epithelial lesion. Beclin 1-mediated chemoresistance was closely linked to the autophagy, Bax underexpression, and the overexpression of Bcl-2, LRP1, MDR1, and ING5. Bioinformatics analysis showed higher Becn1 mRNA expression in intestinal- than diffuse-type carcinomas (P<0.05), and in male than female gastric cancer patients (P<0.05). Becn1 hyperexpression was positively associated with both overall and progression-free survival rates of the cancer patients (P<0.05). Meta-analysis showed that down-regulated Beclin 1 expression in gastric cancer was positively with lymph node metastasis, TNM staging, dedifferentiation and poor prognosis (P<0.05). Becn1-related signal pathways in gastric cancer included prostate, lung, renal, colorectal, endometrial and thyroid cancers, glioma, and leukemia, the metabolism of amino acid, lipid and sugar, and some signal pathways of insulin, MAPK, TRL, VEGF, JAK-STAT, chemokine, p53, lysosome, peroxidome and ubiquitin-mediated protein degradation (P<0.05). These suggested that Beclin 1 might be considered as a potential marker of gastric carcinogenesis, aggressiveness and prognostic prediction, and as a target of gene therapy in gastric cancer.
Analysis of 10 Pediatric Nephrotic Syndrome Cases With Complications of Cerebral Sinovenous Thrombosis
Authors: Rong Liping , Chen Lizhi , Dong Zhi , Zhuang Hongjie , Lin Zhilang , Mo Ying , Jiang Xiaoyun
Published: December 2020

Background: To analyze the clinical characteristics of nephrotic syndrome (NS) with complications of cerebral sinovenous thrombosis (CSVT) in children.

Method: Clinical, radiographic, laboratory, and treatment data obtained from 10 confirmed cases of NS with complications of CSVT were analyzed. All patients were followed up for at least 18 months. CSVT was diagnosed by cerebral computed tomography (CT) and/or magnetic resonance imaging (MRI) with or without magnetic resonance venography (MRV) of the cerebral vessels.

Results: Among 10 cases reported, 4 were steroid-sensitive NS with frequent relapse, 5 were steroid-resistant (three of them had renal biopsies showing two minimal change disease and one IgA nephropathy), and 1 was steroid-sensitive with one relapse. Common clinical manifestations were headache or ophthalmodynia complicated by vomiting, dizziness, convulsion, and coma. Neuropathologic signs were positive in some cases. Papilledema appeared in only one case with winding of vein. Cerebrospinal fluid was examined in three cases with elevated pressure but normal cytological and biochemical results. D dimer and fibrinogen levels were elevated while prothrombin time and activated partial thromboplastin time were shortened. Five out of seven cases who had performed cranial CT were suspicious for cerebral thrombosis. Nine cases had cranial MRI with abnormal signs in seven cases. All of the cases received MRV, confirming the diagnosis of CVST.

Conclusion: Clinical manifestations of NS with CSVT are not specific but varied. Therefore, CSVT should be considered once nervous manifestations present. MRV is a better method in the diagnosis of CSVT.
Angiotensin Type 2 Receptors: Painful, or Not?
Authors: Pulakat Lakshmi , Sumners Colin
Published: December 2020

Pain in response to various types of acute injury can be a protective stimulus to prevent the organism from using the injured part and allow tissue repair and healing. On the other hand, neuropathic pain, defined as ‘pain caused by a lesion or disease of the somatosensory nervous system’, is a debilitating pathology. The TRPA1 neurons in the Dorsal Root Ganglion (DRG) respond to reactive oxygen species (ROS) and induce pain. In acute nerve injury and inflammation, macrophages infiltrating the site of injury undergo an oxidative burst, and generate ROS that promote tissue repair and induce pain via TRPA1. The latter discourages using the injured limb, with a lack of movement helping wound healing. In chronic inflammation caused by diabetes, cancer etc., ROS levels increase systemically and modulate TRPA1 neuronal functions and cause debilitating neuropathic pain. It is important to distinguish between drug targets that elicit protective vs. debilitating pain when developing effective drugs for neuropathic pain. In this context, the connection of the Angiotensin type 2 receptor (AT2R) to neuropathic pain presents an interesting dilemma. Several lines of evidence show that AT2R activation promotes anti-inflammatory and anti-nociceptive signaling, tissue repair, and suppresses ROS in chronic inflammatory models. Conversely, some studies suggest that AT2R antagonists are anti-nociceptive and therefore AT2R is a drug target for neuropathic pain. However, AT2R expression in nociceptive neurons is lacking, indicating that neuronal AT2R is not involved in neuropathic pain. It is also important to consider that Novartis terminated their phase II clinical trial (EMPHENE) to validate that AT2R antagonist EMA401 mitigates post-herpetic neuralgia. This trial, conducted in Australia, United Kingdom, and a number of European and Asian countries in 2019, was discontinued due to pre-clinical drug toxicity data. Moreover, early data from the trial did not show statistically significant positive outcomes. These facts suggest that may AT2R not be the proper drug target for neuropathic pain in humans and its inhibition can be harmful.
Pharmacokinetics and Pharmacodynamics of the Combination of Rhein and Curcumin in the Treatment of Chronic Kidney Disease in Rats
Authors: He Xiaoying , Li Guowei , Chen Yuanyuan , Xiao Qiming , Yu Xinwei , Yu Xixi , Lu Xiaoyang , Xiang Zheng
Published: December 2020

Objectives: The interaction between the components of traditional Chinese medicine (TCM) is an important basis for their synergy. Rhein and curcumin exert various pharmacological activities, including anti-tumour, anti-inflammatory, antioxidant, anti-fibrosis and renoprotective effects. However, no investigation has reported the synergistic anti-fibrosis effect yet. This study aims at determine the pharmacokinetics and pharmacodynamics of the combination of rhein and curcumin in the treatment for chronic kidney disease in rats.

Design: Fifty two male Sprague-Dawley (SD) rats were randomly divided into rhein group, curcumin group and their combination group for pharmacodynamics studies. HE and Masson staining was conducted to observe the changes of renal morphology. Kits were used to detect the level of urea nitrogen (BUN) and creatinine (Scr). For pharmacokinetic study, 36 SD rats were randomly divided into rhein group, curcumin group and a combination group, the content of rhein and curcumin in plasma and renal tissue was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In additon, molecular docking method and cell experiments was used to disclose the interaction mechanism between curcumin and rhein.

Results: The pharmacodynamic results showed that the degree of renal fibrosis was improved obviously by co-administration rhein and curcumin. Meanwhile, compared to single administration, the Cmax and AUC of rhein and curcumin in plasma and renal tissue were enhanced significantly after co-administration. Moreover, the result of molecular docking and cell experiments showed that both two compounds could interact with P-gp, CYP2C9 and CYP2C19.

Conclusion: Together, these findings demonstrated that rhein and curcumin had a synergistic effect in ameliorateing chonic kidney disease, providing an important explanation on the synergistic mechanism of curcumin and rhein from a pharmacokinetic viewpoint.
Case Report: Central Retinal Artery Occlusion in a COVID-19 Patient
Authors: Montesel Andrea , Bucolo Claudio , Mouvet Victoria , Moret Emmanuelle , Eandi Chiara M.
Published: December 2020

We report a case of central retinal artery occlusion (CRAO) in a patient with a previous history of severe COVID-19 disease. This disease has been associated with inflammatory-induced homeostasis changes leading to endothelial dysfunction and a procoagulant state with multi-organ involvement, but the burden of thromboembolic complications in COVID-19 patients is currently unknown. The pathogenesis of retinal artery occlusions is a multifactorial process where inflammation and hypercoagulation state are established risk factors. Even if our experience may represent a coincidental relationship, it is likely that COVID-19 patients could be at risk of developing retinal vascular occlusions. A focused ophthalmological surveillance is advisable to prevent and manage this possible cause of severe vision loss that has an important impact in health care system.
The Impact of Population Migration on the Spread of COVID-19: A Case Study of Guangdong Province and Hunan Province in China
Authors: Xing Guo-Rong , Li Ming-Tao , Li Li , Sun Gui-Quan
Published: December 2020

On the eve of the Spring Festival in 2020, the coronavirus disease 2019 (COVID-19) was reported. Subsequently, the Chinese government at all levels took emergency measures to control the spread of COVID-19 among people. Guangdong and Hunan are large population floating provinces. The spread of COVID-19 is affected by population migration. Before the Spring Festival, Guangdong and Hunan Provinces dominated population export and import, respectively; after the Spring Festival, the trend of population flow was reversed by the resumption of work. Taking Guangdong and Hunan as examples, we establish a three-stage dynamical model to study the impact of population migration on the spread of COVID-19. The result reveals that Guangdong Province mainly emigrated the population and the scale of infection was reduced before the Spring Festival. However, the situation in Hunan Province was just the opposite. After the Spring Festival, work resumption was taking place across China and the migration of Guangdong may cause a second outbreak of the epidemic. While people in Hunan leave the province to work, the migration of population will have little effect on the spread of COVID-19.
Analysis of Acoustic Signals During the Optical Breakdown of Aqueous Solutions of Fe Nanoparticles
Authors: Baimler Ilya V. , Lisitsyn Andrey B. , Serov Dmitriy A. , Astashev Maxim E. , Gudkov Sergey V.
Published: December 2020

The study investigates the spectra of acoustic signals generating during the optical breakdown of colloidal solutions of iron nanoparticles. A characteristic form of the acoustic spectrum has been experimentally established, a distinctive feature of which is the presence of signals from an expanding and collapsing gas bubble. It is shown that the amplitude and area of these acoustic signals depend on the concentration of nanoparticles in the irradiated colloid. The effect of the concentration of nanoparticles on the bubble lifetime corresponding to the time interval between the acoustic spectrum signals corresponding to the birth and cavitation of a gas bubble has been studied.
Assessment of Distinct Electrophysiological Parameters in Rectal Biopsies for the Choice of the Best Diagnosis/Prognosis Biomarkers for Cystic Fibrosis
Authors: Silva Iris A. L. , Duarte Aires , Marson Fernando A. L. , Centeio Raquel , Doušová Tereza , Kunzelmann Karl , Amaral Margarida D.
Published: December 2020

Most cases of Cystic Fibrosis (CF) are diagnosed early in life. However, people with atypical CF forms pose diagnosis dilemmas, requiring laboratory support for diagnosis confirmation/exclusion. Ex vivo analysis of fresh rectal biopsies by Ussing chamber has been the best discriminant biomarker for CF diagnosis/prognosis so far. Here we aimed to evaluate different electrophysiological parameters from Ussing chamber analysis of rectal biopsies from people with CF (PwCF) to establish the one with highest correlations with clinical features as the best CF diagnosis/prognosis biomarker. We analyzed measurements of CFTR-mediated Cl– secretion in rectal biopsies from 143 individuals (∼592 biopsies), the largest cohort so far analyzed by this approach. New parameters were analyzed and compared with the previous biomarker, i.e., the IBMX (I)/Forskolin (F)/Carbachol (C)-stimulated short-circuit current (I’sc–I/F/C). Correlations with clinical features showed that the best parameter corresponded to voltage measurements of the I/F + (I/F/CCH) response (VI/F+I/F/C), with higher correlations vs. I’sc–I/F/C for: sweat chloride (59 vs. 52%), fecal elastase (69 vs. 55%) and lung function, measured by FEV1 (27 vs. 20%). Altogether data show that VI/F+I/F/C is the most sensitive, reproducible, and robust predictive biomarker for CF diagnosis/prognosis effectively discriminating classical, atypical CF and non-CF groups.
Oxygen in Red Blood Cell Concentrates: Influence of Donors’ Characteristics and Blood Processing
Authors: Bardyn Manon , Martin Agathe , Dögnitz Nora , Abonnenc Mélanie , Dunham Andrew , Yoshida Tatsuro , Prudent Michel
Published: December 2020

Objective: Unexpectedly wide distribution (<10 to >90%) of hemoglobin oxygen saturation (sO2) within red cell concentrates (RCCs) has recently been observed. Causes of such variability are not yet completely explained whereas the roles of oxygen and oxidative lesions during the storage of RCCs are known. The objectives of the present study are to characterize sO2 distribution in RCCs produced in a Swiss blood center and to investigate the influence of processing and donors’ characteristics.

Methods: The level of sO2 was measured in 1701 leukocyte-depleted RCCs derived from whole blood donations in both top–bottom (TB; component filtered, SAGM) and top–top (TT; whole blood filtration, PAGGSM) RCCs. The sO2 value was measured non-invasively through the PVC bag prior to storage by resonance Raman spectroscopy. Gender, age, blood type, hemoglobin level, and living altitude of donors, as well as process method and time-to-process were recorded.

Results: Overall, the sO2 exhibited a wide non-Gaussian distribution with a mean of 51.2 ± 18.5%. Use of top-top kits resulted in a 16% higher sO2 (P < 0.0001) than with top-bottom ones. Waiting time before processing only had a modest impact, but the blood processing itself reduced the sO2 by almost 12% (P < 0.0001). sO2 was also significantly affected by some donors’ characteristics. RCCs from men exhibited 25% higher sO2 (P < 0.0001) than those donated by women. Multivariate analysis revealed that the apparent correlation observed with hemoglobin level and age was actually due to multicollinearity with the sex variable. Finally, we noticed no significant differences across blood type but found that altitude of residence was associated with the sO2 (i.e., higher in higher living place).

Conclusion: These data confirm wide sO2 distribution in RCCs reported recently. The sO2 was impacted by the processing and also by donors’ characteristics such as the gender and the living altitude, but not by the hemoglobin level, blood group and donor age. This study provides new hints on the factors influencing red blood cells storage lesions, since they are known to be related to O2 content within the bags, giving clues to better process and to better store RCCs and therefore potentially improve the efficacy of transfusion.
Indirect Selection on Flower Color in Silene littorea
Authors: Rodríguez-Castañeda Nancy L. , Ortiz Pedro L. , Arista Montserrat , Narbona Eduardo , Buide Mª Luisa
Published: December 2020

Flower color, as other floral traits, may suffer conflicting selective pressures mediated by both mutualists and antagonists. The maintenance of intraspecific flower color variability has been usually explained as a result of direct selection by biotic agents. However, flower color might also be under indirect selection through correlated traits, since correlations among flower traits are frequent. In this study, we aimed to find out how flower color variability is maintained in two nearby populations ofSilene littoreathat consistently differ in the proportions of white-flowered plants. To do that, we assessed natural selection on floral color and correlated traits by means of phenotypic selection analysis and path analysis. Strong directional selection on floral display and flower production was found in both populations through either male or female fitness. Flower color had a negative indirect effect on the total male and female fitness in Melide population, as plants with lighter corollas produced more flowers. In contrast, in Barra population, plants with darker corollas produced more flowers and have darker calices, which in turn were selected. Our results suggest that the prevalence of white-flowered plants in Melide and pink-flowered plants in Barra is a result of indirect selection through correlated flower traits and not a result of direct selection of either pollinators or herbivores on color.
Constructing a Core Collection of the Medicinal Plant Angelica biserrata Using Genetic and Metabolic Data
Authors: Liu Man , Hu Xin , Wang Xu , Zhang Jingjing , Peng Xubing , Hu Zhigang , Liu Yifei
Published: December 2020

Angelica biserratais an important medicinal plant in Chinese traditional medicine. Its roots, which are known asDuhuoin Chinese, are broadly applied to treat inflammation, arthritis, and headache. With increasing market demand, the wild resources ofA. biserratahave been overexploited, and conservation, assessment of genetic resources and breeding for this species is needed. Here, we sequenced the transcriptome ofA. biserrataand developed simple sequence repeat (SSR) markers from it to construct a core collection based on 208 samples collected from Changyang-related regions. A total of 132 alleles were obtained for 17 SSR loci used with the polymorphic information content (PIC) ranging from 0.44 to 0.83. Abundant genetic diversity was inferred by Shannon’s information index (1.51), observed (0.57) and expected heterozygosity (0.72). The clustering analysis resulted into two sample groups and analysis of molecular variance (AMOVA) showed only 6% genetic variation existed among populations. A further metabolic analysis of these samples revealed the main coumarin contents, such as osthole and columbianadin. According to the genetic and metabolic data, we adopted the least distance stepwise sampling strategy to construct seven preliminary core collections, of which the 20CC collection, which possessed 42A. biserrataindividuals accounting for 90.20% of the genetic diversity of the original germplasm, represented the best core collection. This study will contribute to the conservation and management ofA. biserratawild germplasm resources and provide a material basis for future selection and breeding of this medicinal plant.
Less Is More—Cyclists-Triathlete’s 30 min Cycling Time-Trial Performance Is Impaired With Multiple Feedback Compared to a Single Feedback
Authors: Bayne Freya , Racinais Sebastien , Mileva Katya , Hunter Steve , Gaoua Nadia
Published: December 2020

Purpose: The purpose of this article was to (i) compare different modes of feedback (multiple vs. single) on 30 min cycling time-trial performance in non-cyclist’s and cyclists-triathletes, and (ii) investigate cyclists-triathlete’s information acquisition.

Methods: 20 participants (10 non-cyclists, 10 cyclists-triathletes) performed two 30 min self-paced cycling time-trials (TT, ∼5–7 days apart) with either a single feedback (elapsed time) or multiple feedback (power output, elapsed distance, elapsed time, cadence, speed, and heart rate). Cyclists-triathlete’s information acquisition was also monitored during the multiple feedback trial via an eye tracker. Perceptual measurements of task motivation, ratings of perceived exertion (RPE) and affect were collected every 5 min. Performance variables (power output, cadence, distance, speed) and heart rate were recorded continuously.

Results: Cyclists-triathletes average power output was greater compared to non-cyclists with both multiple feedback (227.99 ± 42.02 W; 137.27 ± 27.63 W; P < 0.05) and single feedback (287.9 ± 60.07 W; 131.13 ± 25.53 W). Non-cyclist’s performance did not differ between multiple and single feedback (p > 0.05). Whereas, cyclists-triathletes 30 min cycling time-trial performance was impaired with multiple feedback (227.99 ± 42.02 W) compared to single feedback (287.9 ± 60.07 W; p < 0.05), despite adopting and reporting a similar pacing strategy and perceptual responses (p > 0.05). Cyclists-triathlete’s primary and secondary objects of regard were power (64.95 s) and elapsed time (64.46 s). However, total glance time during multiple feedback decreased from the first 5 min (75.67 s) to the last 5 min (22.34 s).

Conclusion: Cyclists-triathletes indoor 30 min cycling TT performance was impaired with multiple feedback compared to single feedback. Whereas non-cyclist’s performance did not differ between multiple and single feedback. Cyclists-triathletes glanced at power and time which corresponds with the wireless sensor networks they use during training. However, total glance time during multiple feedback decreased over time, and therefore, overloading athletes with feedback may decrease performance in cyclists-triathletes.
Machine Learning-Based Data Mining Method for Sentiment Analysis of the Sewol Ferry Disaster's Effect on Social Stress
Authors: Lee Min-Joon , Lee Tae-Ro , Lee Seo-Joon , Jang Jin-Soo , Kim Eung Ju
Published: December 2020

The Sewol Ferry Disaster which took place in 16th of April, 2014, was a national level disaster in South Korea that caused severe social distress nation-wide. No research at the domestic level thus far has examined the influence of the disaster on social stress through a sentiment analysis of social media data. Data extracted from YouTube, Twitter, and Facebook were used in this study. The population was users who were randomly selected from the aforementioned social media platforms who had posted texts related to the disaster from April 2014 to March 2015. ANOVA was used for statistical comparison between negative, neutral, and positive sentiments under a 95% confidence level. For NLP-based data mining results, bar graph and word cloud analysis as well as analyses of phrases, entities, and queries were implemented. Research results showed a significantly negative sentiment on all social media platforms. This was mainly related to fundamental agents such as ex-president Park and her related political parties and politicians. YouTube, Twitter, and Facebook results showed negative sentiment in phrases (63.5, 69.4, and 58.9%, respectively), entity (81.1, 69.9, and 76.0%, respectively), and query topic (75.0, 85.4, and 75.0%, respectively). All results were statistically significant (p< 0.001). This research provides scientific evidence of the negative psychological impact of the disaster on the Korean population. This study is significant because it is the first research to conduct sentiment analysis of data extracted from the three largest existing social media platforms regarding the issue of the disaster.