bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive Training for Mild Traumatic Brain Injury and Posttraumatic Stress Disorder
Authors: Samuelson Kristin W. , Engle Krista , Abadjian Linda , Jordan Joshua , Bartel Alisa , Talbot Margaret , Powers Tyler , Bryan Lori , Benight Charles
Published: November 2020

Although there is evidence of mild cognitive impairments for many individuals with mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD), little research evaluating the effectiveness of cognitive training interventions has been conducted. This randomized controlled trial examined the effectiveness of a 9-h group cognitive training targeting higher-order functions, Strategic Memory Advanced Reasoning Training (SMART), compared to a 9-h psychoeducational control group in improving neurocognitive functioning in adults with mTBI and PTSD. A sample of 124 adults with histories of mild TBI (n = 117) and/or current diagnoses of PTSD (n = 84) were randomized into SMART (n = 66) or Brain Health Workshop (BHW; n = 58) and assessed at three time points: baseline, following training, and 6 months later. Participants completed a battery of neurocognitive tests, including a test of gist reasoning (a function directly targeted by SMART) as well as tests of verbal, visual, and working memory and executive functioning, functions commonly found to be mildly impaired in mTBI and PTSD. The two groups were compared on trajectories of change over time using linear mixed-effects models with restricted maximum likelihood (LMM). Contrary to our hypothesis that SMART would result in superior improvements compared to BHW, both groups displayed statistically and clinically significant improvements on measures of memory, executive functioning, and gist reasoning. Over 60% of the sample showed clinically significant improvements, indicating that gains can be found through psychoeducation alone. A longer SMART protocol may be warranted for clinical samples in order to observe gains over the comparison group.
Familial Idiopathic Intracranial Hypertension in Two Non-obese Chinese Sisters
Authors: Qiao Lei , Wei Yanping
Published: November 2020

Background: Familial idiopathic intracranial hypertension (FIIH) is a rare condition, the etiology of which is unclear.

Aims: To describe two non-obese Chinese sisters who met the criteria of FIIH and to analyze the clinical features and prognosis of FIIH.

Methods: The clinical course, treatment, and prognosis of these two patients were analyzed retrospectively. Meanwhile, all the literature of familial IIH (FIIH) was reviewed.

Results: These two sisters presented with headaches and visual impairment in their mid-thirties. Magnetic resonance imaging (MRI) of the brain was unremarkable except for partial empty sella. No comorbidities or defined causes were detected. Headaches were partially relieved by dehydrated medicine, whereas the visual impairment persisted.

Conclusion: In cases where patients present with headaches, empty sella are found on an MRI, and there is visual impairment with or without papilla edema, intracranial hypertension should be excluded. Furthermore, we should pay more attention to the relatives of those patients with increased intracranial hypertension.
BrainWave Nets: Are Sparse Dynamic Models Susceptible to Brain Manipulation Experimentation?
Authors: Nascimento Diego C. , Pinto-Orellana Marco A. , Leite Joao P. , Edwards Dylan J. , Louzada Francisco , Santos Taiza E. G.
Published: November 2020

Sparse time series models have shown promise in estimating contemporaneous and ongoing brain connectivity. This paper was motivated by a neuroscience experiment using EEG signals as the outcome of our established interventional protocol, a new method in neurorehabilitation toward developing a treatment for visual verticality disorder in post-stroke patients. To analyze the [complex outcome measure (EEG)] that reflects neural-network functioning and processing in more specific ways regarding traditional analyses, we make a comparison among sparse time series models (classic VAR, GLASSO, TSCGM, and TSCGM-modified with non-linear and iterative optimizations) combined with a graphical approach, such as a Dynamic Chain Graph Model (DCGM). These dynamic graphical models were useful in assessing the role of estimating the brain network structure and describing its causal relationship. In addition, the class of DCGM was able to visualize and compare experimental conditions and brain frequency domains [using finite impulse response (FIR) filter]. Moreover, using multilayer networks, the results corroborate with the susceptibility of sparse dynamic models, bypassing the false positives problem in estimation algorithms. We conclude that applying sparse dynamic models to EEG data may be useful for describing intervention-relocated changes in brain connectivity.
Disrupted Lipid Raft Shuttling of FcεRI by n-3 Polyunsaturated Fatty Acid Is Associated With Ligation of G Protein-Coupled Receptor 120 (GPR120) in Human Mast Cell Line LAD2
Authors: Wang Xiaofeng , Ilarraza Ramses , Tancowny Brian P. , Alam Syed Benazir , Kulka Marianna
Published: November 2020

n-3 polyunsaturated fatty acids (PUFA) influences a variety of disease conditions, such as hypertension, heart disease, diabetes, cancer and allergic diseases, by modulating membrane constitution, inhibiting production of proinflammatory eicosanoids and cytokines, and binding to cell surface and nuclear receptors. We have previously shown that n-3 PUFA inhibit mast cell functions by disrupting high affinity IgE receptor (FcεRI) lipid raft partitioning and subsequent suppression of FcεRI signaling in mouse bone marrow-derived mast cells. However, it is still largely unknown how n-3 PUFA modulate human mast cell function, which could be attributed to multiple mechanisms. Using a human mast cell line (LAD2), we have shown similar modulating effects of n-3 PUFA on FcεRI lipid raft shuttling, FcεRI signaling, and mediator release after cell activation through FcεRI. We have further shown that these effects are at least partially associated with ligation of G protein-coupled receptor 120 expressed on LAD2 cells. This observation has advanced our mechanistic knowledge of n-3 PUFA's effect on mast cells and demonstrated the interplay between n-3 PUFA, lipid rafts, FcεRI, and G protein-coupled receptor 120. Future research in this direction may present new targets for nutritional intervention and therapeutic agents.
Osimertinib Resistance With a Novel EGFR L858R/A859S/Y891D Triple Mutation in a Patient With Non-Small Cell Lung Cancer: A Case Report
Authors: Yang Yanli , Zhang Xing , Wang Ruixiao , Qin Jiayue , Wang Juan , Li Zhimin , Song Xia
Published: November 2020

Targeted drug therapy based on the types of epidermal growth factor receptor (EGFR) gene mutations has been widely used in the diagnosis and treatment of patients with non-small cell lung cancer (NSCLC). With the development of next-generation sequencing (NGS) technology, more and more EGFR-tyrosine kinase inhibitor (TKI) resistance mutation sites have been revealed. Here, we report a novel EGFR L858R/A859S/Y891D triple mutation in plasma-derived circulating tumor DNA (ctDNA) was identified in a 53-year-old male patient with NSCLC resistant to osimertinib treatment, using an ultra-deep (20,000×) 160-gene panel through the NGS platform. Our case confirms that dynamic monitoring of liquid biopsy based on ctDNA is conducive to the selection of targeted therapy and the realization of the patient’s full course management.
A Ticket to Ride: The Implications of Direct Intercellular Communication via Tunneling Nanotubes in Peritoneal and Other Invasive Malignancies
Authors: Lou Emil
Published: November 2020

It is well established that the role of the tumor microenvironment (TME) in cancer progression and therapeutic resistance is crucial, but many of the underlying mechanisms are still being elucidated. Even with better understanding of molecular oncology and identification of genomic drivers of these processes, there has been a relative lag in identifying and appreciating the cellular drivers of both invasion and resistance. Intercellular communication is a vital process that unifies and synchronizes the diverse components of the tumoral infrastructure. Elucidation of the role of extracellular vesicles (EVs) over the past decade has cast a brighter light on this field. And yet even with this advance, in addition to diffusible soluble factor-mediated paracrine and endocrine cell communication as well as EVs, additional niches of intratumoral communication are filled by other modes of intercellular transfer. Tunneling nanotubes (TNTs), tumor microtubes (TMs), and other similar intercellular channels are long filamentous actin-based cellular conduits (in most epithelial cancer cell types, ~15-500 µm in length; 50–1000+ nm in width). They extend and form direct connections between distant cells, serving as conduits for direct intercellular transfer of cell cargo, such as mitochondria, exosomes, and microRNAs; however, many of their functional roles in mediating tumor growth remain unknown. These conduits literally create a physical bridge to create a syncytial network of dispersed cells amidst the intercellular stroma-rich matrix. Emerging evidence suggests that they provide a cellular mechanism for induction and emergence of drug resistance and contribute to increased invasive and metastatic potential. They have been imaged in vitro and also in vivo and ex vivo in tumors from human patients as well as animal models, thus not only proving their existence in the TME, but opening further speculation about their exact role in the dynamic niche of tumor ecosystems. TNT cellular networks are upregulated between cancer and stromal cells under hypoxic and other conditions of physiologic and metabolic stress. Furthermore, they can connect malignant cells to benign cells, including vascular endothelial cells. The field of investigation of TNT-mediated tumor-stromal, and tumor-tumor, cell-cell communication is gaining momentum. The mixture of conditions in the microenvironment exemplified by hypoxia-induced ovarian cancer TNTs playing a crucial role in tumor growth, as just one example, is a potential avenue of investigation that will uncover their role in relation to other known factors, including EVs. If the role of cancer heterocellular signaling via TNTs in the TME is proven to be crucial, then disrupting formation and maintenance of TNTs represents a novel therapeutic approach for ovarian and other similarly invasive peritoneal cancers.
Biotherapeutic Antibodies for the Treatment of Head and Neck Cancer: Current Approaches and Future Considerations of Photothermal Therapies
Authors: Al Qaraghuli Mohammed M.
Published: November 2020

Head and neck cancer (HNC) is a heterogeneous disease that includes a variety of tumors originating in the hypopharynx, oropharynx, lip, oral cavity, nasopharynx, or larynx. HNC is the sixth most common malignancy worldwide and affects thousands of people in terms of incidence and mortality. Various factors can trigger the development of the disease such as smoking, alcohol consumption, and repetitive viral infections. HNC is currently treated by single or multimodality approaches, which are based on surgery, radiotherapy, chemotherapy, and biotherapeutic antibodies. The latter approach will be the focus of this article. There are currently three approved antibodies against HNCs (cetuximab, nivolumab, and pembrolizumab), and 48 antibodies under development. The majority of these antibodies are of humanized (23 antibodies) or human (19 antibodies) origins, and subclass IgG1 represents a total of 32 antibodies. In addition, three antibody drug conjugates (ADCs: telisotuzumab-vedotin, indatuximab-ravtansine, and W0101) and two bispecific antibodies (GBR 1372 and ABL001) have been under development. Despite the remarkable success of antibodies in treating different tumors, success was limited in HNCs. This limitation is attributed to efficacy, resistance, and the appearance of various side effects. However, the efficacy of these antibodies could be enhanced through conjugation to gold nanoparticles (GNPs). These conjugates combine the high specificity of antibodies with unique spectral properties of GNPs to generate a treatment approach known as photothermal therapy. This approach can provide promising outcomes due to the ability of GNPs to convert light into heat, which can specifically destroy cancer cells and treat HNC in an effective manner.
Survival Outcomes of Radical Prostatectomy + Extended Pelvic Lymph Node Dissection and Radiotherapy in Prostate Cancer Patients With a Risk of Lymph Node Invasion Over 5%: A Population-Based Analysis
Authors: Chen Junru , Ni Yuchao , Sun Guangxi , Zhu Sha , Zhao Jinge , Wang Zhipeng , Zhang Haoran , Zhu Xudong , Zhang Xingming , Dai Jindong , Shen Pengfei , Zeng Hao
Published: November 2020

Purpose

We aimed to compare the efficacy of radical prostatectomy (RP) + extended pelvic lymph node dissection (ePLND) and radiotherapy (RT) in localized prostate cancer (PCa) patients with a risk of lymph node invasion (LNI) over 5%.

Methods

The Surveillance, Epidemiology, and End Results (SEER) databases were used to identify patients with PCa from 2010 to 2014. Propensity score matching (PSM) was performed to balance baseline characteristics between patients in different treatment groups. Kaplan-Meier curves and Cox regression were used to assess the effects of treatments on cancer-specific survival (CSS) and overall survival (OS).

Results

Overall 20584 patients were included in this study, with 4,057 and 16,527 patients receiving RP + ePLND and RT, respectively. After PSM, patients with RP + ePLND had similar CSS (5-year CSS rate: 97.8% vs. 97.2%, P=0.310) but longer OS (5-year OS rate: 96.0% vs. 90.8%, P<0.001) compared to those receiving RT. When separating RT cohort into external beam radiotherapy (EBRT) group and EBRT+ brachytherapy (BT) group, treatments with RP + ePLND and EBRT+ BT achieved equivalent OS and were both superior to EBRT alone (5-year OS rate: 96.0% vs. 94.4% vs. 90.0%, P<0.001). Subgroup analyses and multivariate analyses further confirmed the superiority of RP + ePLND and EBRT+ BT.

Conclusion

RP + ePLND and EBRT + BT were associated with better survival outcomes compared to EBRT alone in PCa patients with a probability of LNI over 5%. However, no survival difference was observed between RP + ePLND and EBRT + BT.
Effectiveness of Pharmacist–Physician Collaborative Management for Patients With Idiopathic Pulmonary Fibrosis Receiving Pirfenidone
Authors: Satsuma Yukari , Ikesue Hiroaki , Kusuda Kaori , Maeda Mami , Muroi Nobuyuki , Mori Ryobu , Kogo Mariko , Hirabayashi Ryosuke , Nagata Kazuma , Nakagawa Atsushi , Tachikawa Ryo , Tomii Keisuke , Hashida Tohru
Published: November 2020

Background: Pirfenidone is an anti-fibrotic agent used to treat patients with idiopathic pulmonary fibrosis (IPF). Managing adverse drug events and ensuring compliance with pirfenidone treatment for a prolonged period are important to reduce the rate of disease progression. To maximize the benefits of pirfenidone treatment, we established and evaluated an ambulatory care pharmacy practice, a model of pharmacist–physician collaborative management, for patients receiving pirfenidone.

Methods: We conducted a retrospective chart review of 76 consecutive patients treated with pirfenidone in the Kobe City Medical Center General Hospital, Japan, between January 2012 and January 2019. The first group (61 patients) received pirfenidone treatment as conventional management, whereas the second group (15 patients) started pirfenidone based on collaborative pharmacist–physician management. The drug discontinuation rate and time to drug discontinuation were compared between the groups. To analyze factors associated with pirfenidone discontinuation, we used a multivariate Cox regression analysis to evaluate the baseline characteristics of patients, including those receiving the collaborative management. Clinical outcomes were compared using a propensity score matched analysis.

Results: In the collaborative management group, pharmacists made 56 suggestions, including suggestions for supportive care (51 suggestions), to the physicians. Among these suggestions, 52 were accepted by the physicians. The discontinuation rates at 3 [6.7% (1/15) vs. 26.2% (16/61)] and 6 [9.1% (1/11) vs. 36.1% (22/61)] months were lower in the collaborative management group than in the conventional management group. Multivariate analysis revealed that collaborative management [hazard ratio (HR) 0.34, 95% CI 0.08–0.96, p = 0.041] and predicted baseline forced vital capacity <60% (HR 2.13, 95% CI 1.17–3.85, p = 0.015) were significantly associated with pirfenidone discontinuation. The time to drug discontinuation was also significantly longer in the collaborative management group than in the conventional management group (p = 0.034, log-rank test). Propensity score matched analysis confirmed a significant correlation between collaborative management and drug discontinuation time (HR 0.20, 95% CI 0.03–0.84, p = 0.027).

Conclusions: We established an ambulatory care pharmacy practice for out-patients with IPF receiving pirfenidone. The results suggest that collaborative management may help prevent pirfenidone discontinuation compared with conventional management.
Clinical Review: Navitoclax as a Pro-Apoptotic and Anti-Fibrotic Agent
Authors: Mohamad Anuar Nur Najmi , Nor Hisam Nur Syahidah , Liew Sze Ling , Ugusman Azizah
Published: November 2020

B-cell lymphoma 2 (BCL-2) family proteins primarily work as a programmed cell death regulator, whereby multiple interactions between them determine cell survival. This explains the two major classes of BCL-2 proteins which are anti-apoptotic and pro-apoptotic proteins. The anti-apoptotic proteins are attractive targets for BCL-2 family inhibitors, which result in the augmentation of the intrinsic apoptotic pathway. BCL-2 family inhibitors have been studied extensively for novel targeted therapies in various cancer types, fibrotic diseases, aging-related as well as autoimmune diseases. Navitoclax is one of them and it has been discovered to have a high affinity toward BCL-2 anti-apoptotic proteins, including BCL-2, BCL-W and B-cell lymphoma-extra-large. Navitoclax has been demonstrated as a single agent or in combination with other drugs to successfully ameliorate tumor progression and fibrosis development. To date, navitoclax has entered phase I and phase II clinical studies. Navitoclax alone potently treats small cell lung cancer and acute lymphocytic leukemia, whilst in combination therapy for solid tumors, it enhances the therapeutic effect of other chemotherapeutic agents. A low platelet count has always associated with single navitoclax treatments, though this effect is tolerable. Moreover, the efficacy of navitoclax is determined by the expression of several BCL-2 family members. Here, we elucidate the complex mechanisms of navitoclax as a pro-apoptotic agent, and review the early and current clinical studies of navitoclax alone as well as with other drugs. Additionally, some suggestions on the development of navitoclax clinical studies are presented in the future prospects section.
The Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Pinostrobin in Rats: Ultra-High-Performance Liquid Chromatography Coupled With Linear Trap Quadrupole Orbitrap Mass Spectrometry Studies
Authors: Sun Xiaoya , Liu Xiaojun , Chen Suiqing
Published: November 2020

Pinostrobin is a natural flavonoid found in various plants, well known for its wide range of pharmacological activities. However, there are few reports regarding the pharmacokinetics, tissue distribution, metabolism, and excretion of pinostrobin in rats after oral administration as a single compound. Therefore, we established a method using ultra-high-performance liquid chromatography coupled with linear trap quadrupole orbitrap mass spectrometry (UPLC-LTQ orbitrap-MS/MS) to determine pinostrobin and its metabolites in rat plasma, urine, feces, bile, and tissue homogenates. Pharmacokinetic parameters were measured. The large apparent volume of distribution implied that pinostrobin preferentially bound to tissues and preferably remained within the body. Based on previous pharmacological studies of its antiulcer, anti-HP, anti-inflammatory, and antioxidant activities, pinostrobin is mostly distributed in the gastrointestinal tract, indicating its potential as an effective component of traditional Chinese medicines for the treatment of peptic ulcers. Furthermore, 30 flavonoid metabolites were screened using UPLC-LTQ orbitrap-MS/MS. The metabolism pathways (mainly hydroxylation, demethylation, glucuronidation, and sulfation) of pinostrobin in rats have also been proposed. A small amount of pinostrobin in its parent form is excreted through the urine, feces, and bile, indicating that it is mainly metabolized in vivo. In this study, we systemically investigated the pharmacokinetics, tissue distribution, metabolism, and excretion of pinostrobin in rats. Our results provide a significant basis for the clinical development and application of pinostrobin as well as traditional Chinese medicines containing pinostrobin.
Suppression of Urokinase-Type Plasminogen Activator Receptor by Docosahexaenoic Acid Mediated by Heme Oxygenase-1 in 12-O-Tetradecanoylphorbol-13-Acetate-Induced Human Endothelial Cells
Authors: Lian Sen , Li Shinan , Sah Dhiraj Kumar , Kim Nam Ho , Lakshmanan Vinoth‐Kumar , Jung Young Do
Published: November 2020

Urokinase-type plasminogen activator receptor (uPAR) plays a crucial role in inflammation and tumor metastasis. Docosahexaenoic acid (DHA), a representative omega-3 polyunsaturated fatty acid, has been shown to exhibit anti-inflammatory and anti-tumor properties. However, the mechanism by which DHA negatively regulates uPAR expression is not yet understood. The aim of this study was to investigate the effect of DHA on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced uPAR expression and potential role of heme oxygenase-1 (HO-1) in DHA-induced inhibition of uPAR in human endothelial ECV304 cells. Results showed that TPA induced uPAR expression in a time dependent manner, while DHA inhibited uPAR expression in a concentration-dependent manner. Moreover, treatment with DHA induced HO-1 expression in a time- and concentration-dependent manner. In addition, DHA-induced inhibition of uPAR expression and cell invasion in TPA-stimulated cells was reversed by si-HO-1 RNA. Induction of HO-1 by ferric protoporphyrin IX (FePP) inhibited TPA-induced uPAR expression, and this effect was abolished by treatment with the HO-1 inhibitor tin protoporphyrin IX (SnPP). Additionally, carbon monoxide, an HO-1 product, attenuated TPA-induced uPAR expression and cell invasion. Collectively, these data suggest a novel role of DHA-induced HO-1 in reducing uPAR expression and cell invasion in human endothelial ECV304 cells.
Vigna radiata (L.) R. Wilczek Extract Inhibits Influenza A Virus by Targeting Viral Attachment, Penetration, Assembly, and Release
Authors: Lo Chieh-Wen , Pi Chia-Chen , Chen You-Ting , Chen Hui-Wen
Published: November 2020

Vigna radiata (L.) R. Wilczek (mung bean) is a Chinese functional food with antioxidant, antimicrobial and anti-inflammatory activities. However, little is known about its antiviral activity. We aimed to investigate the antiviral activity and mechanisms of action of Vigna radiata extract (VRE) against influenza virus. HPLC was conducted to analyze the components of the VRE. The anti-influenza viral activity of VRE in Mardin-Darby canine kidney (MDCK) cells was evaluated by virus titration assays, hemagglutination assays, quantitative RT-PCR assays, cellular α-glucosidase activity assays and neuraminidase activity assays. Chromatographic profiling analysis identified two major flavonoids, vitexin and isovitexin, in the ethanol extract of Vigna radiata. Through in vitro studies, we showed that VRE, at concentrations up to 2,000 μg/ml, exhibited no cytotoxicity in MDCK cells. VRE protected cells from influenza virus-induced cytopathic effects and significantly inhibited viral replication in a concentration-dependent manner. A detailed time-of-addition assay revealed that VRE may act on both the early and late stages of the viral life cycle. We demonstrated that 1) VRE inhibits virus entry by directly blocking the HA protein of influenza virus; 2) VRE inhibits virus entry by directly binding to cellular receptors; 3) VRE inhibits virus penetration; 4) VRE inhibits virus assembly by blocking cellular α-glucosidase activity, thus reducing HA protein trafficking to the cell surface; and 5) VRE inhibits virus release by inhibiting viral neuraminidase activity. In summary, Vigna radiata extract potently interferes with two different subtypes of influenza viruses at multiple steps during the infectious cycle, demonstrating its broad-spectrum potential as an anti-influenza preventive and therapeutic agent. Continued development of Vigna radiata-derived products into antiviral therapeutics is warranted.
The Potential Roles of Artemisinin and Its Derivatives in the Treatment of Type 2 Diabetes Mellitus
Authors: Jiang Ya-yi , Shui Jia-cheng , Zhang Bo-xun , Chin Jia-wei , Yue Ren-song
Published: November 2020

Type 2 diabetes mellitus (T2DM) is a chronic disease that has become a global public health problem. Studies on T2DM prevention and treatment mostly focus on discovering therapeutic drugs. Artemisinin and its derivatives were originally used as antimalarial treatments. In recent years, the roles of artemisinins in T2DM have attracted much attention. Artemisinin treatments not only attenuate insulin resistance and restore islet ß-cell function in T2DM but also have potential therapeutic effects on diabetic complications, including diabetic kidney disease, cognitive impairment, diabetic retinopathy, and diabetic cardiovascular disease. Many in vitro and in vivo experiments have confirmed the therapeutic utility of artemisinin and its derivatives on T2DM, but no article has systematically demonstrated the specific role artemisinin plays in the treatment of T2DM. This review summarizes the potential therapeutic effects and mechanism of artemisinin and its derivatives in T2DM and associated complications, providing a reference for subsequent related research.
Severe Acute Respiratory Syndrome Coronavirus-2 Induces Cytokine Storm and Inflammation During Coronavirus Disease 19: Perspectives and Possible Therapeutic Approaches
Authors: Mannino Federica , Bitto Alessandra , Irrera Natasha
Published: November 2020

The new coronavirus outbreak was first identified in Wuhan, China, in December 2019, and has turned out to be a global health emergency, affecting millions of people worldwide. Coronavirus disease 19 (COVID-19), caused by the SARS-CoV-2 virus, can manifest with flu-like symptoms and can be complicated by severe pneumonia with acute respiratory distress syndrome (ARDS); however a large percentage of infected individuals do not have symptoms but contribute to the spread of the disease. Severe acute respiratory syndrome coronavirus-2 infection has become a global public health emergency since no available treatment seems effective and it is hard to manage the several complications caused by an intense release of cytokines. This paper reviews the current options on drugs used to reduce the deadly effects of the cytokine storm.
A Review of Edible Jujube, the Ziziphus jujuba Fruit: A Heath Food Supplement for Anemia Prevalence
Authors: Chen Jianping , Tsim Karl W. K.
Published: November 2020

The fruits of Ziziphus jujuba, commonly known as jujube, red date or Chinese date, are taken as fresh or dried food, and as traditional medicine worldwide due to high nutritional and health values. Traditionally in China, jujube is considered as a medicinal fruit that is being used in treating blood deficiency. In this review, the beneficial effects of jujubes on the hematopoietic functions are summarized and discussed. As illustrated in cell and animal models, the application of jujube extract possessed beneficial effects, including regulation of erythropoiesis via activation of hypoxia inducible factor-induced erythropoietin, potential capacity in recycling heme iron during erythrophagocytosis and bi-directional regulation of immune response. Thus, the blood-nourishing function of jujube is being proposed here. Flavonoid, polysaccharide and triterpenoid within jujube could serve as the potential active ingredients accounting for the aforementioned health benefits. Taken together, these findings provide several lines of evidence for further development of jujube as supplementary products for prevention and/or treatment of anemia.
pH-Sensitive and Long-Circulation Nanoparticles for Near-Infrared Fluorescence Imaging-Monitored and Chemo-Photothermal Synergistic Treatment Against Gastric Cancer
Authors: Zhou Yun , Sun Xuanzi , Zhou Liansuo , Zhang Xiaozhi
Published: November 2020

Gastrectomy is the primary therapeutic option for gastric cancer. Postoperative treatment also plays a crucial role. The strategy to improve the postoperative prognosis of gastric cancer requires a combined system that includes a more efficient synergistic treatment and real-time monitoring after surgery. In this study, photothermal-chemotherapy combined nanoparticles (PCC NPs) were prepared via π-π stacking to perform chemo-photothermal synergistic therapy and continuous imaging of gastric cancer. PCC NPs had a spherical morphology and good monodispersity under aqueous conditions. The hydrodynamic diameter of PCC NPs was 59.4 ± 3.6 nm. PCC NPs possessed strong encapsulation ability, and the maximum drug loading rate was approximately 37%. The NPs exhibited extraordinary stability and pH-response release profiles. The NPs were rapidly heated under irradiation. The maximum temperature was close to 58°C. PCC NPs showed good biocompatibility both in vitro and in vivo. Moreover, the NPs could effectively be used for in vivo continuous monitoring of gastric cancer. After one injection, the fluorescent signal remained in tumor tissues for nearly a week. The inhibitory effect of PCC NPs was evaluated in a gastric cancer cell line and xenograft mouse model. Both in vitro and in vivo evaluations demonstrated that PCC NPs could be used for chemo-photothermal synergistic therapy. The suppression effect of PCC NPs was significantly better than that of single chemotherapy or photothermal treatment. This study lays the foundation for the development of novel postoperative treatments for gastric cancer.
Preclinical Challenges in Proton Minibeam Radiotherapy: Physics and Biomedical Aspects
Authors: Datzmann Gerd , Sammer Matthias , Girst Stefanie , Mayerhofer Michael , Dollinger Günther , Reindl Judith
Published: November 2020

The concept of spatial fractionation in radiotherapy was developed for better sparing of normal tissue in the entrance channel of radiation. Spatial fractionation utilizing proton minibeam radiotherapy (pMBRT) promises to be advantageous compared to X-ray minibeams due to higher dose conformity at the tumor. Preclinical in vivo experiments conducted with pMBRT in mouse ear models or in rat brains support the prospects, but the research about the radiobiological mechanisms and the search for adequate application parameters delivering the most beneficial minibeam therapy is still in its infancy. Concerning preclinical research, we consider glioma, non-small cell lung cancer and hepatocellular carcinoma as the most promising targets and propose investigating the effects on healthy tissue, especially neuronal cells and abdominal organs. The experimental setups for preclinical pMBRT used so far follow different technological approaches, and experience technical limitations when addressing the current questions in the field. We review the crucial physics parameters necessary for proton minibeam production and link them to the technological challenges to be solved for providing an optimal research environment. We consider focusing of pencil or planar minibeams in a scanning approach superior compared to collimation due to less beam halos, higher peak-to-valley dose ratios and higher achievable dose rates. A possible solution to serve such a focusing system with a high-quality proton beam at all relevant energies is identified to be a 3 GHz radio-frequency linear accelerator. We propose using a 16 MeV proton beam from an existing tandem accelerator injected into a linear post-accelerator, boosted up to 70 MeV, and finally delivered to an imaging and positioning end-station suitable for small animal irradiation. Ion-optical simulations show that this combination can generate focused proton minibeams with sizes down to 0.1 mm at 18 nA mean proton current - sufficient for all relevant preclinical experiments. This technology is expected to offer powerful and versatile tools for unleashing structured and advanced preclinical pMBRT studies at the limits and also has the potential to enable a next step into precision tumor therapy.
Dynamic Network Connectedness of Bitcoin Markets: Evidence from Realized Volatility
Authors: Chen Shuanglian , Dong Hao
Published: November 2020

In this paper, we explore the volatility spillovers across different Bitcoin markets. We decompose the realized volatility into common and idiosyncratic volatilities, as well as the good and bad volatilities. Then the asymmetry in volatility spillovers between Bitcoin markets is measured by the DY (Diebold and Yilmaz) index. In addition, we construct statistics to test the asymmetry in volatility spillovers between different Bitcoin markets. The results are achieved as follows. The spillovers of systematic and idiosyncratic volatilities dominate the connectedness among different Bitcoin markets. In addition, the idiosyncratic volatility spillovers are more easily influenced by policies. Good volatility spillovers dominate the Bitcoin markets and change over time. The further results suggest that there is significant asymmetry between systematic and idiosyncratic volatility spillovers in the Bitcoin markets, while the asymmetries between good and bad volatility spillovers are heterogeneous in different markets. The findings in this paper can provide some suggestions for regulators controlling market stability and investors generating investment strategies.
The Influence of Chromosomal Polymorphism on Embryo Development and Embryonic Molecular Karyotype in Preimplantation Genetic Testing for Chromosomal Translocation
Authors: Li Gang , Shi Weiyi , Niu Wenbin , Xu Jiawei , Guo Yihong , Su Yingchun , Sun Yingpu
Published: November 2020

Traditionally, chromosomal polymorphisms (CPMs) are normal genetic variants in individuals with no phenotypic variations. However, some studies have shown that CPM is related to reproductive diseases. We explored the influence of CPM on embryonic development and molecular karyotype in chromosomal translocation (CT) patients undergoing preimplantation genetic testing (PGT) between February 2013 and May 2019. Twenty-six cases with CPM and 56 controls with normal chromosomes were included. Furthermore, a 1:4 match pair analysis by female age included 39 cases with CTCPM and 185 controls with CT. There was no statistical difference in fertilization rate (78.48% vs. 78.33%), cleavage rate on Day 3 (90.32% vs. 89.16%), blastocyst rate (60.00% vs. 60.80%), and the high-quality blastocyst rate (36.31% vs. 35.22%) between CPM and normal chromosomes. The high-quality blastocyst rate of CTCPM was significantly lower than that for CT (26.78% vs. 38.89%). Moreover, there was no statistical difference in fertilization rate (70.65% vs. 70.37%), cleavage rate on Day 3 (88.67% vs. 89.53%), and blastocyst rate (48.48% vs. 53.17%) between CTCPM and CT. In addition, one CTCPM spouse had a lower high-quality blastocyst rate, especially of males with CTCPM. Abnormal embryo rates of CTCPM were significantly higher than those for CT (78.64% vs. 68.93%). Abnormal embryo rates were higher in both CTCPM and CPM paternal carriers with CT partners, respectively. For CT, CTCPM may have an impact on the high-quality blastocyst rate and embryonic molecular karyotype, especially in male patients. Patients with CTCPM are relatively rare, but this population would benefit from being explored using a larger sample size.
UDP-Glycosyltransferases and Albendazole Metabolism in the Juvenile Stages of Haemonchus contortus
Authors: Kellerová Pavlína , Navrátilová Martina , Nguyen Linh Thuy , Dimunová Diana , Raisová Stuchlíková Lucie , Štěrbová Karolína , Skálová Lenka , Matoušková Petra
Published: November 2020

The nematode Haemonchus contortus, a gastrointestinal parasite of ruminants, can severely burden livestock production. Although anthelmintics are the mainstay in the treatment of haemonchosis, their efficacy diminishes due to drug-resistance development in H. contortus. An increased anthelmintics inactivation via biotransformation belongs to a significant drug-resistance mechanism in H. contortus. UDP-glycosyltransferases (UGTs) participate in the metabolic inactivation of anthelmintics and other xenobiotic substrates through their conjugation with activated sugar, which drives the elimination of the xenobiotics due to enhanced solubility. The UGTs family, in terms of the biotransformation of commonly used anthelmintics, has been well described in adults as a target stage. In contrast, the free-living juvenile stages of H. contortus have attracted less attention. The expression of UGTs considerably varies throughout the life cycle of the juvenile nematodes, suggesting their different roles. Furthermore, the constitutive expression in a susceptible strain with two resistant strains shows several resistance-related changes in UGTs expression, and the exposure of juvenile stages of H. contortus to albendazole (ABZ) and ABZ-sulfoxide (ABZSO; in sublethal concentrations) leads to the increased expression of several UGTs. The anthelmintic drug ABZ and its primary metabolite ABZSO biotransformation, tested in the juvenile stages, shows significant differences between susceptible and resistant strain. Moreover, higher amounts of glycosidated metabolites of ABZ are formed in the resistant strain. Our results show similarly, as in adults, the UGTs and glycosidations significant for resistance-related differences in ABZ biotransformation and warrant further investigation in their individual functions.
Insights Into the Early Gene Regulatory Network Controlling Neural Crest and Placode Fate Choices at the Neural Border
Authors: Seal Subham , Monsoro-Burq Anne H.
Published: November 2020

The neural crest (NC) cells and cranial placodes are two ectoderm-derived innovations in vertebrates that led to the acquisition of a complex head structure required for a predatory lifestyle. They both originate from the neural border (NB), a portion of the ectoderm located between the neural plate (NP), and the lateral non-neural ectoderm. The NC gives rise to a vast array of tissues and cell types such as peripheral neurons and glial cells, melanocytes, secretory cells, and cranial skeletal and connective cells. Together with cells derived from the cranial placodes, which contribute to sensory organs in the head, the NC also forms the cranial sensory ganglia. Multiplein vivostudies in different model systems have uncovered the signaling pathways and genetic factors that govern the positioning, development, and differentiation of these tissues. In this literature review, we give an overview of NC and placode development, focusing on the early gene regulatory network that controls the formation of the NB during early embryonic stages, and later dictates the choice between the NC and placode progenitor fates.
Testing the Process Dissociation Procedure by Behavioral and Neuroimaging Data: The Establishment of the Mutually Exclusive Theory and the Improved PDP
Authors: Zhang Jianxin , Wang Xiangpeng , Huang Jianping , Chen Antao , Liu Dianzhi
Published: November 2020

The process dissociation procedure (PDP) of implicit sequence learning states that the correct inclusion-task response contains the incorrect exclusion-task response. However, there has been no research to test the hypothesis. The current study used a single variable (Stimulus Onset Asynchrony SOA: 850 ms vs. 1350 ms) between-subjects design, with pre-task resting-state fMRI, to test and improve the classical PDP to the mutually exclusive theory (MET). (1) Behavioral data and neuroimaging data demonstrated that the classical PDP has not been validated. In the SOA = 850 ms group, the correct inclusion-task response was at chance, but the incorrect exclusion-task response occurred greater than chance. In the SOA = 850 ms group, the two responses were not correlated, but in the SOA = 1,350 ms group and putting the two groups together, the two responses were in contrast to each other. In each group, brain areas whose amplitude of low frequency fluctuations (ALFFs) in the resting-state related to the two responses were either completely different or opposite to one another. However, the results were perfectly consistent with the MET proposed by the present study which suggests that the correct inclusion-task response is equal to the correct exclusion-task response is equal toC+A1, and the incorrect exclusion-task response is equal toA2.Cdenotes the controlled response andA1andA2denote two different automatic responses. (2) The improved PDP was proposed to categorize the 12 kinds of triplets as delineating four knowledge types, namely non-acquisition of knowledge, uncontrollable knowledge, half-controllable knowledge, and controllable knowledge with the MET. ALFFs in the resting-state could predict the four knowledge types of the improved PDP among two groups. The participants’ control of the four knowledge types (degree of consciousness) gradually improved. Correspondingly, the brain areas in the resting-state positively related to the four knowledge types, gradually changed from the sensory and motor network to the somatic sensorimotor network, and then to the implicit learning network, and then to the consciousness network. The brain areas in the resting-state negatively related to the four knowledge types gradually changed from the consciousness network to the sensory and motor network. As SOA increased, the brain areas associated with almost all the four knowledge types changed. (3) The inhomogeneous hypothesis of the MET is best suited to interpret behavioral and neuroimaging data; it states that the same components among the four knowledge types are not homogeneous, and the same knowledge types are not homogeneous between the two SOA groups.
Risk Factors for Sexual Offending in Self-Referred Men With Pedophilic Disorder: A Swedish Case-Control Study
Authors: Wittström Felix , Långström Niklas , Landgren Valdemar , Rahm Christoffer
Published: November 2020

Background

The risk of child sexual abuse among non-forensic, non-correctional patients with Pedophilic Disorder (PD) is largely unknown.

Methods

We recruited a consecutive sample of 55 help-seeking, non-correctional adult men diagnosed with DSM-5 PD at a university-affiliated sexual medicine outpatient unit in Sweden. PD participants were compared with 57 age-matched, non-clinical control men on four literature-based dynamic risk domains and self-rated child sexual abuse risk.

Results

PD participants scored higher than controls on all tested domains (0–3 points); expectedly so for pedophilic attraction (2.5 vs. 0.0, Cohen’s d = 2.40, 95% confidence interval (CI): [1.91–2.89]), but also for sexual preoccupation (1.6 vs. 1.0, d = 1.11, 95% CI: [0.71–1.51]), impaired self-regulation (1.4 vs. 1.0, d = 0.44, 95% CI: [0.06 to 0.81]), impaired cognitive empathy and antisocial traits (0.9 vs. 0.1, d = 1.18, 95% CI: [0.78–1.59]), and self-rated child sexual abuse risk (1.0 vs. 0.0, d = 1.56, 95% CI: [1.13–1.98]). When summarizing all five domains into a pre-specified composite score (0–15 points), PD subjects scored substantially higher than matched control men (7.5 vs. 2.1, d = 2.12, 95% CI: [1.65–2.59]). Five (9%) PD participants self-reported any previous conviction for a contact child sexual offense and eight (15%) for possession of child sexual abuse material or non-contact sexual offending (adult or child victim). Eighteen subjects (34%) acknowledged past week, child-related sexual behaviors.

Conclusion

Self-referred, help-seeking men with PD scored higher (small to very large effect sizes) than non-clinical control men on psychiatric measures of dynamic risk of child sexual abuse suggested in prior research with correctional samples diagnosed with PD. Our findings, including the composite risk measure, might inform clinical practice, but needs validation against actual sexual offending behavior.
Sociometric Popularity, Perceived Peer Support, and Self-Concept in Adolescence
Authors: Fernández-Zabala Arantza , Ramos-Díaz Estibaliz , Rodríguez-Fernández Arantzazu , Núñez Juan L.
Published: November 2020

The objective of this study is to analyze the role that peer support plays in the incidence relationships between sociometric popularity and general self-concept based on sociometer theory. A total of 676 randomly selected secondary school students from the Basque Country (49.6% boys and 50.4% girls) between 12 and 18 years of age (M = 14.32, DT = 1.36) participated voluntarily. All of them completed a sociometric questionnaire (SOCIOMET), the Family and Friends Support Questionnaire (AFA-R), and the Dimensional Self-concept Questionnaire (AUDIM-33). Several models of structural equations were tested. The results indicate that sociometric popularity is linked to self-concept through the perceived social support of peers. These results are discussed within the framework of positive psychology and its practical implications in the school context.
Authoritarianism, Conspiracy Beliefs, Gender and COVID-19: Links Between Individual Differences and Concern About COVID-19, Mask Wearing Behaviors, and the Tendency to Blame China for the Virus
Authors: Prichard Eric C. , Christman Stephen D.
Published: November 2020

The present study investigated variables potentially associated with a lack of concern about COVID-19 and belief in the conspiracy theory that China is responsible for the virus. In particular, the study looked at Authoritarianism, Conspiracy Beliefs, gender, and consistency of handedness as predictors of nine Likert-type items gauging attitudes, behavior, and beliefs regarding the virus. Initial analyses showed that Authoritarianism predicted less concern about the impact of the virus on health, less mask wearing, and a stronger belief in China’s responsibility for the illness. Conspiracy Beliefs were associated with a stronger belief in China’s responsibility. Women expressed greater degrees of concern about their own and others’ health and about the financial wellbeing of others. In order to reduce the number of dimensions, and thus the number of tests that could yield a type one error, the nine items were then submitted to a principal components analysis which yielded a “Concern about COVID” factor and a “Blame for China” factor. Authoritarianism is generally associated with less concern about the virus. In addition, men showed less concern about the virus overall than women. Both Authoritarianism and Conspiracy Beliefs accounted for unique variance in blame on China for the virus.