bluuebunny/crossref_metadata_2025 huggingface dataset:
Antioxidants and vitamins in clinical conditions
Authors: Zadák Z , Hyšpler R , Tichá A , Hronek M , Fikrová P , Rathouská J , Hrnčiariková D , Štětina R
Published: March 2021

Various reactive oxygen species (ROS) may be produced from
normal biochemical, essential metabolic processes or from
external sources as exposure to a variety of agents presented in
the environment. Lipids, proteins, carbohydrates and DNA are all
capable of reacting with ROS and can be implicated in etiology of
various human disorders (rheumatoid arthritis, reperfusion injury,
atherosclerosis, lung diseases etc.). In the organism damage by
ROS is counteracted with natural antioxidants (glutathione
peroxidases, superoxide dismutases, catalase, glutathione,
ubiquinol, uric acid, and essential minerals) and nutritional
antioxidants from diet (i.e. vitamins E, C, carotenoids). Possible
mechanisms of nutritional depletion and side effects of high
intake are in the article described.
Probabilistic Bearing Capacity of a Pavement Resting on Fibre Reinforced Embankment Considering Soil Spatial Variability
Authors: Choudhuri Kouseya , Chakraborty Debarghya
Published: March 2021

This paper intends to examine the influence of spatial variability of soil properties on the probabilistic bearing capacity of a pavement located on the crest of a fibre reinforced embankment. An anisotropic random field, in combination with the finite difference method, is used to carry out the probabilistic analyses. The cohesion and internal friction angle of the soil are assumed to be lognormally distributed. The Monte Carlo simulations are carried out to obtain the mean and coefficient of variation of the pavement bearing capacity. The mean bearing capacity of the pavement is found to decrease with the increase in horizontal scale of fluctuation for a constant vertical scale of fluctuation; whereas, the coefficient of variation of the bearing capacity increases with the increase in horizontal scale of fluctuation. However, both the mean and coefficient of variation of bearing capacity of the pavement are observed to be increasing with the increase in vertical scale of fluctuation for a constant horizontal scale of fluctuation. Apart from the different scales of fluctuation, the effects of out of the plane length of the embankment and randomness in soil properties on the probabilistic bearing capacity are also investigated in the present study.
Meiotic Recombination Defects and Premature Ovarian Insufficiency
Authors: Huang Chengzi , Guo Ting , Qin Yingying
Published: March 2021

Premature ovarian insufficiency (POI) is the depletion of ovarian function before 40 years of age due to insufficient oocyte formation or accelerated follicle atresia. Approximately 1–5% of women below 40 years old are affected by POI. The etiology of POI is heterogeneous, including genetic disorders, autoimmune diseases, infection, iatrogenic factors, and environmental toxins. Genetic factors account for 20–25% of patients. However, more than half of the patients were idiopathic. With the widespread application of next-generation sequencing (NGS), the genetic spectrum of POI has been expanded, especially the latest identification in meiosis and DNA repair-related genes. During meiotic prophase I, the key processes include DNA double-strand break (DSB) formation and subsequent homologous recombination (HR), which are essential for chromosome segregation at the first meiotic division and genome diversity of oocytes. Many animal models with defective meiotic recombination present with meiotic arrest, DSB accumulation, and oocyte apoptosis, which are similar to human POI phenotype. In the article, based on different stages of meiotic recombination, including DSB formation, DSB end processing, single-strand invasion, intermediate processing, recombination, and resolution and essential proteins involved in synaptonemal complex (SC), cohesion complex, and fanconi anemia (FA) pathway, we reviewed the individual gene mutations identified in POI patients and the potential candidate genes for POI pathogenesis, which will shed new light on the genetic architecture of POI and facilitate risk prediction, ovarian protection, and early intervention for POI women.
Distribution of Iron on FCC Catalyst and Its Effect on Catalyst Performance
Authors: Liao Yitao , Liu Tao , Du Xiaohui , Gao Xionghou
Published: March 2021

The effects of different iron contamination content on the formation of iron nodules and the performance of FCC catalysts have been studied by cyclic deactivation treatment using iron naphthenate. The catalysts were characterized by X-ray diffraction, N2 adsorption-desorption, and SEM. The catalysts’ performance was evaluated by the Advanced Cracking Evaluation device. It has been found that there will be obvious nodulation on the catalyst when the iron concentration exceeds 7,400 μg/g. With the iron deposition from 53 μg/g to 11,690 μg/g, the crystal structure of zeolite will not be destroyed by iron. The surface area and pore volume of the catalyst decreased significantly; the surface area decreased from 125.3 m2/g to 91.0 m2/g, and the pore volume decreased from 0.21 cm3/g to 0.16 cm3/g. The studies also showed that the increase of iron deposition will lead to the decrease of catalytic reaction efficiency. With the iron deposition from 53 μg/g to 11,690 μg/g, the conversion decreased by 4.83%. Under the same 78 wt.% conversion, bottoms yield and coke yield increased by 2.15% and 1.31%, while gasoline yield and LCO yield decreased by 2.59% and 2.16%, respectively. The real state of the industrial iron contaminated equilibrium catalyst can be mimicked by using the cyclic deactivation method.
Is HPV the Novel Target in Male Idiopathic Infertility? A Systematic Review of the Literature
Authors: Muscianisi Francesco , De Toni Luca , Giorato Gloria , Carosso Andrea , Foresta Carlo , Garolla Andrea
Published: March 2021

Infertility is an important health problem that affects up to 16% of couples worldwide. Male infertility is responsible for about 50% of the cases, and the various causes of male infertility may be classified in pre-testicular (for example hypothalamic diseases), testicular, and post-testicular (for example obstructive pathologies of seminal ducts) causes. Sexually transmitted infections (STI) are increasingly widely accepted by researchers and clinicians as etiological factors of male infertility. In particular, several recent reports have documented the presence of HPV in seminal fluid and observed that sperm infection can also be present in sexually active asymptomatic male and infertile patients. In this review, we aimed to perform a systematic review of the whole body of literature exploring the impact of HPV infection in natural and assisted fertility outcomes, from both an experimental and a clinical point of view. Starting from in-vitro studies in animals up to in-vivo studies in humans, we aimed to study and evaluate the weight of this infection as a possible cause of idiopathic infertility in males with any known cause of conception failure.
Prognostic Association of TERC, TERT Gene Polymorphism, and Leukocyte Telomere Length in Acute Heart Failure: A Prospective Study
Authors: Li Yanxiu , Cheang Iokfai , Zhang Zhongwen , Yao Wenming , Zhou Yanli , Zhang Haifeng , Liu Yun , Zuo Xiangrong , Li Xinli , Cao Quan
Published: March 2021

Background

Telomere length and telomerase are associated in development of cardiovascular diseases. Study aims to investigate the associations of TERC and TERT gene polymorphism and leukocyte telomere length (LTL) in the prognosis of acute heart failure (AHF).

Methods

Total 322 patients with AHF were enrolled and divided into death and survival group according to all-cause mortality within 18 months. Seven single nucleotide polymorphisms (SNPs) of TERC and TERT were selected. Baseline characteristics, genotype distribution and polymorphic allele frequency, and genetic model were initially analyzed. Genotypes and the LTL were determined for further analysis.

Results

Compared to carrying homozygous wild genotype, the risk of death in patients with mutated alleles of four SNPs- rs12696304(G>C), rs10936599(T>C), rs1317082(G>A), and rs10936601(T>C) of TERC were significantly higher. The dominant models of above were independently associated with mortality. In recessive models, rs10936599 and rs1317082 of TERC, rs7726159 of TERT were independently associated with long-term mortality. Further analysis showed, in haplotype consisting with TERC - rs12696304, rs10936599, rs1317082, and rs10936601, mutant alleles CCAC and wild alleles GTGT were significant difference between groups (P<0.05). CCAC is a risk factor and GTGT is a protective factor for AHF patients. Relative LTL decreased over age, but showed no difference between groups and genotypes.

Conclusions

The SNPs of TERC and TERT are associated with the prognosis of AHF, and are the independent risk factors for predicting 18-month mortality in AHF.
A Web-Based Software Platform for Restoration-Oriented Species Selection Based on Plant Functional Traits
Authors: Wang Chen , Jian Shuguang , Ren Hai , Yan Junhua , Liu Nan
Published: March 2021

Plant functional traits are fundamental to the understanding of plant adaptations and distributions. Recently, scientists proposed a trait-based species selection theory to support the selection of suitable plant species to restore the degraded ecosystems, to prevent the invasive exotic species and to manage the sustainable ecosystems. Based on this theory, in a previous study, we developed a species screening model and successfully applied it to a project where plant species were selected for restoring a tropical coral island. However, during this process we learned that a software platform is necessary to automate the selection process because it can flexible to assist users. Here, we developed a generalized software platform called the “Restoration Plant Species Selection (RPSS) Platform.” This flexible software is designed to assist users in selecting plant species for particular purposes (e.g., restore the degraded ecosystems and others). It is written in R language and integrated with external R packages, including the packages that computing similarity indexes, providing graphic outputs, and offering web functions. The software has a web-based graphical user interface that allows users to execute required functions via checkboxes and buttons. The platform has cross-platform functionality, which means that it can run on all common operating systems (e.g., Windows, Linux, macOS, and others). We also illustrate a successful case study in which the software platform was used to select suitable plant species for restoration purpose. The objective of this paper is to introduce the newly developed software platform RPSS and to provide useful guidances on using it for various applications. At this step, we also realized that the software platform should be constantly updated (e.g., add new features) in the future. Based on the existing successful application and the possible updates, we believe that our RPSS software platform will have broader applications in the future.
Genetic Identification of Edible Bird’s Nest in Thailand Based on ARMS-PCR
Authors: Lv Dongyong , Fan Yaohua , Zhong Wanhua , Lonan Piyanuch , Liu Kunfeng , Wu Maoyong , Wu Yina , Liang Yueliang , Lai Xiaoping , Li Geng , Yu Liangwen
Published: March 2021

Edible bird’s nest (EBN) is a popular delicacy in the Asian Pacific region originating from Indonesia, Malaysia, Thailand and Vietnam, which consist of various potential medicine value in Traditional Chinese Medicine (TCM). Thailand is one of the main exporters of EBN. However, the genetic information of EBN, a key part of molecular biology, has yet to be reported in Thailand. It is necessary to explore the genetic information of EBN in Thailand based on a quick and simple method to help protect the rights and interests of consumers. This research aimed to systematically evaluate different methods of extracting EBN DNA to improve the efficiency of the analysis of cytochrome b (Cytb) and NADH dehydrogenase subunit 2 (ND2) gene sequences, the establishment of phylogenetic trees, and the genetic information of EBN in Thailand. Additionally, we aimed to develop a quick and simple method for identifying EBN from different species based on the genetic information and amplification-refractory mutation system PCR (ARMS-PCR). By comparing the four methods [cetyltrimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS), kit and guanidinium isothiocyanate methods] for EBN extraction, we found that the guanidinium isothiocyanate method was the optimal extraction method. Phylogenetic trees generated on the basis of Cytb and ND2 gene analyses showed that 26 samples of house EBN and 4 samples of cave EBN came from Aerodramus fuciphagus and Aerodramus maximus, respectively. In addition, to distinguish different samples from different species of Apodiformes, we designed 4 polymerase chain reaction (PCR) amplification primers based on the ND2 gene sequences of A. fuciphagus and A. maximus. The ARMS-PCR results showed band lengths for A. fuciphagus EBN of 533, 402, and 201 bp, while those for A. maximus EBN were 463, 317, and 201 bp. Collectively, the results showed that ARMS-PCR is a fast and simple method for the genetic identification of EBN based on designing specific original identification primers.
Genomic Loci Affecting Milk Production in German Black Pied Cattle (DSN)
Authors: Korkuć Paula , Arends Danny , May Katharina , König Sven , Brockmann Gudrun A.
Published: March 2021

German Black Pied cattle (DSN) is an endangered population of about 2,550 dual-purpose cattle in Germany. Having a milk yield of about 2,500 kg less than the predominant dairy breed Holstein, the preservation of DSN is supported by the German government and the EU. The identification of the genomic loci affecting milk production in DSN can provide a basis for selection decisions for genetic improvement of DSN in order to increase market chances through the improvement of milk yield. A genome-wide association analysis of 30 milk traits was conducted in different lactation periods and numbers. Association using multiple linear regression models in R was performed on 1,490 DSN cattle genotyped with BovineSNP50 SNP-chip. 41 significant and 20 suggestive SNPs affecting milk production traits in DSN were identified, as well as 15 additional SNPs for protein content which are less reliable due to high inflation. The most significant effects on milk yield in DSN were detected on chromosomes 1, 6, and 20. The region on chromosome 6 was located nearby the casein gene cluster and the corresponding haplotype overlapped the CSN3 gene (casein kappa). Associations for fat and protein yield and content were also detected. High correlation between traits of the same lactation period or number led to some SNPs being significant for multiple investigated traits. Half of all identified SNPs have been reported in other studies, previously. 15 SNPs were associated with the same traits in other breeds. The other associated SNPs have been reported previously for traits such as exterior, health, meat and carcass, production, and reproduction traits. No association could be detected between DGAT1 and other known milk genes with milk production traits despite the close relationship between DSN and Holstein. The results of this study confirmed that many SNPs identified in other breeds as associated with milk traits also affect milk traits in dual-purpose DSN cattle and can be used for further genetic analysis to identify genes and causal variants that affect milk production in DSN cattle.
Cross Kingdom Immunity: The Role of Immune Receptors and Downstream Signaling in Animal and Plant Cell Death
Authors: Roudaire Thibault , Héloir Marie-Claire , Wendehenne David , Zadoroznyj Aymeric , Dubrez Laurence , Poinssot Benoit
Published: March 2021

Both plants and animals are endowed with sophisticated innate immune systems to combat microbial attack. In these multicellular eukaryotes, innate immunity implies the presence of cell surface receptors and intracellular receptors able to detect danger signal referred as damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). Membrane-associated pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), C-type lectin receptors (CLRs), receptor-like kinases (RLKs), and receptor-like proteins (RLPs) are employed by these organisms for sensing different invasion patterns before triggering antimicrobial defenses that can be associated with a form of regulated cell death. Intracellularly, animals nucleotide-binding and oligomerization domain (NOD)-like receptors or plants nucleotide-binding domain (NBD)-containing leucine rich repeats (NLRs) immune receptors likely detect effectors injected into the host cell by the pathogen to hijack the immune signaling cascade. Interestingly, during the co-evolution between the hosts and their invaders, key cross-kingdom cell death-signaling macromolecular NLR-complexes have been selected, such as the inflammasome in mammals and the recently discovered resistosome in plants. In both cases, a regulated cell death located at the site of infection constitutes a very effective mean for blocking the pathogen spread and protecting the whole organism from invasion. This review aims to describe the immune mechanisms in animals and plants, mainly focusing on cell death signaling pathways, in order to highlight recent advances that could be used on one side or the other to identify the missing signaling elements between the perception of the invasion pattern by immune receptors, the induction of defenses or the transmission of danger signals to other cells. Although knowledge of plant immunity is less advanced, these organisms have certain advantages allowing easier identification of signaling events, regulators and executors of cell death, which could then be exploited directly for crop protection purposes or by analogy for medical research.
Incidence and Risk of Infection Associated With Fingolimod in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis of 8,448 Patients From 12 Randomized Controlled Trials
Authors: Zhao Zhao , Ma Chun-Lai , Gu Zhi-Chun , Dong Yue , Lv Yang , Zhong Ming-Kang
Published: March 2021

Background and Aims: There is a controversy regarding whether fingolimod is associated with an increased risk of infection in patients with multiple sclerosis (MS). We performed a systematic review and meta-analysis of data from randomized controlled trials (RCTs) to determine the risk of infection in these patients.

Methods: We systematically searched PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov from inception to April 8, 2020, to identify RCTs that reported the occurrence of infection in patients with MS treated with fingolimod. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated using the random-effects model.

Results: Twelve RCTs including 8,448 patients were eligible. Compared with the control (placebo and other active treatments), fingolimod significantly increased the risk of infection (RR, 1.16; 95% CI, 1.07–1.27; I2, 81%), regardless of whether the infection was a general infection (RR, 1.14; 95% CI, 1.05–1.25; I2, 78%), or a serious infection (RR, 1.49; 95% CI, 1.06–2.10; I2, 0%). Analyses of subgroups found that fingolimod significantly increased the risk of lower respiratory infection (RR, 1.48; 95% CI, 1.19–1.85; I2, 0%) and herpes virus infection (RR, 1.34; 95% CI, 1.01–1.78; I2, 9%). There appears to be no dose-dependent increase in the risk of infection associated with fingolimod (0.5 mg: RR, 1.15; 95% CI, 1.07–1.25; I2, 91%; 1.25 mg: RR, 1.11; 95% CI, 0.97–1.28; I2, 81%; Pinteraction = 0.66).

Conclusions: Compared with a placebo and other active treatments, fingolimod was associated with a 16% increase in the risk of infection, especially lower respiratory infection and herpes virus infection. The risk of infection associated with fingolimod might not be dose related.
Function of Macrophages in Disease: Current Understanding on Molecular Mechanisms
Authors: Zhang Chunye , Yang Ming , Ericsson Aaron C.
Published: March 2021

Tissue-resident macrophages (TRMs) are heterogeneous populations originating either from monocytes or embryonic progenitors, and distribute in lymphoid and non-lymphoid tissues. TRMs play diverse roles in many physiological processes, including metabolic function, clearance of cellular debris, and tissue remodeling and defense. Macrophages can be polarized to different functional phenotypes depending on their origin and tissue microenvironment. Specific macrophage subpopulations are associated with disease progression. In studies of fate-mapping and single-cell RNA sequencing methodologies, several critical molecules have been identified to induce the change of macrophage function. These molecules are potential markers for diagnosis and selective targets for novel macrophage-mediated treatment. In this review, we discuss some of the recent findings regarding less-known molecules and new functions of well-known molecules. Understanding the mechanisms of these molecules in macrophages has the potential to yield new macrophage-mediated treatments or diagnostic approaches to disease.
Germline Genetic Variants of Viral Entry and Innate Immunity May Influence Susceptibility to SARS-CoV-2 Infection: Toward a Polygenic Risk Score for Risk Stratification
Authors: Grolmusz Vince Kornél , Bozsik Anikó , Papp János , Patócs Attila
Published: March 2021

The ongoing COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2 has affected all aspects of human society with a special focus on healthcare. Although older patients with preexisting chronic illnesses are more prone to develop severe complications, younger, healthy individuals might also exhibit serious manifestations. Previous studies directed to detect genetic susceptibility factors for earlier epidemics have provided evidence of certain protective variations. Following SARS-CoV-2 exposure, viral entry into cells followed by recognition and response by the innate immunity are key determinants of COVID-19 development. In the present review our aim was to conduct a thorough review of the literature on the role of single nucleotide polymorphisms (SNPs) as key agents affecting the viral entry of SARS-CoV-2 and innate immunity. Several SNPs within the scope of our approach were found to alter susceptibility to various bacterial and viral infections. Additionally, a multitude of studies confirmed genetic associations between the analyzed genes and autoimmune diseases, underlining the versatile immune consequences of these variants. Based on confirmed associations it is highly plausible that the SNPs affecting viral entry and innate immunity might confer altered susceptibility to SARS-CoV-2 infection and its complex clinical consequences. Anticipating several COVID-19 genomic susceptibility loci based on the ongoing genome wide association studies, our review also proposes that a well-established polygenic risk score would be able to clinically leverage the acquired knowledge.
Evaluation of the Thermal Inactivation of a Salmonella Serotype Oranienburg Strain During Cocoa Roasting at Conditions Relevant to the Fine Chocolate Industry
Authors: Yan Runan , Pinto Gabriella , Taylor-Roseman Rebecca , Cogan Karen , D’Alesandre Greg , Kovac Jasna
Published: March 2021

Cocoa roasting produces and enhances distinct flavor of chocolate and acts as a critical control point for inactivation of foodborne pathogens in chocolate production. In this study, the inactivation kinetics of Salmonella enterica subsp. enterica serotype Oranienburg strain was assessed on whole cocoa beans using roasting protocols relevant to the fine chocolate industry. Beans were inoculated with 107–108 log10 CFU/bean of Salmonella Oranienburg and roasted at 100–150°C for 2–100 min. A greater than 5 log10 reduction of S. Oranienburg was experimentally achieved after 10-min roasting at 150°C. Data were fitted using log-linear and Weibull models. The log-linear models indicated that the roasting times (D) needed to achieve a decimal reduction of Salmonella at 100, 110, 115, 120, 130, and 140°C were 33.34, 18.57, 12.92, 10.50, 4.20, and 1.90 min, respectively. A Weibull model indicated a decrease in the Salmonella inactivation rate over time (β < 1). Statistical analysis indicated that the Weibull model fitted the data better compared to a log-linear model. These data demonstrate the efficacy of cocoa roasting in inactivation of Salmonella and may be used to guide food safety decision-making.
Microfluidics in Sickle Cell Disease Research: State of the Art and a Perspective Beyond the Flow Problem
Authors: Aich Anupam , Lamarre Yann , Sacomani Daniel Pereira , Kashima Simone , Covas Dimas Tadeu , de la Torre Lucimara Gaziola
Published: March 2021

Sickle cell disease (SCD) is the monogenic hemoglobinopathy where mutated sickle hemoglobin molecules polymerize to form long fibers under deoxygenated state and deform red blood cells (RBCs) into predominantly sickle form. Sickled RBCs stick to the vascular bed and obstruct blood flow in extreme conditions, leading to acute painful vaso-occlusion crises (VOCs) – the leading cause of mortality in SCD. Being a blood disorder of deformed RBCs, SCD manifests a wide-range of organ-specific clinical complications of life (in addition to chronic pain) such as stroke, acute chest syndrome (ACS) and pulmonary hypertension in the lung, nephropathy, auto-splenectomy, and splenomegaly, hand-foot syndrome, leg ulcer, stress erythropoiesis, osteonecrosis and osteoporosis. The physiological inception for VOC was initially thought to be only a fluid flow problem in microvascular space originated from increased viscosity due to aggregates of sickled RBCs; however, over the last three decades, multiple molecular and cellular mechanisms have been identified that aid the VOCin vivo. Activation of adhesion molecules in vascular endothelium and on RBC membranes, activated neutrophils and platelets, increased viscosity of the blood, and fluid physics driving sickled and deformed RBCs to the vascular wall (known as margination of flow) – all of these come together to orchestrate VOC. Microfluidic technology in sickle research was primarily adopted to benefit from mimicking the microvascular network to observe RBC flow under low oxygen conditions as models of VOC. However, over the last decade, microfluidics has evolved as a valuable tool to extract biophysical characteristics of sickle red cells, measure deformability of sickle red cells under simulated oxygen gradient and shear, drug testing,in vitromodels of intercellular interaction on endothelialized or adhesion molecule-functionalized channels to understand adhesion in sickle microenvironment, characterizing biomechanics and microrheology, biomarker identification, and last but not least, for developing point-of-care diagnostic technologies for low resource setting. Several of these platforms have already demonstrated true potential to be translated from bench to bedside. Emerging microfluidics-based technologies for studying heterotypic cell–cell interactions, organ-on-chip application and drug dosage screening can be employed to sickle research field due to their wide-ranging advantages.
Emerging Therapeutic Approaches to Combat COVID-19: Present Status and Future Perspectives
Authors: Vivekanandhan Karthik , Shanmugam Poornima , Barabadi Hamed , Arumugam Vigneshwaran , Daniel Raj Daniel Paul Raj Dharun , Sivasubramanian Manikandan , Ramasamy Subbaiya , Anand Krishnan , Boomi Pandi , Chandrasekaran Balakumar , Arokiyaraj Selvaraj , Saravanan Muthupandian
Published: March 2021

Coronavirus disease (COVID-19) has emerged as a fast-paced epidemic in late 2019 which is disrupting life-saving immunization services. SARS-CoV-2 is a highly transmissible virus and an infectious disease that has caused fear among people across the world. The worldwide emergence and rapid expansion of SARS-CoV-2 emphasizes the need for exploring innovative therapeutic approaches to combat SARS-CoV-2. The efficacy of some antiviral drugs such as remdesivir, favipiravir, umifenovir, etc., are still tested against SARS-CoV-2. Additionally, there is a large global effort to develop vaccines for the protection against COVID-19. Because vaccines seem the best solution to control the pandemic but time is required for its development, pre-clinical/clinical trials, approval from FDA and scale-up. The nano-based approach is another promising approach to combat COVID-19 owing to unique physicochemical properties of nanomaterials. Peptide based vaccines emerged as promising vaccine candidates for SARS-CoV-2. The study emphasizes the current therapeutic approaches against SARS-CoV-2 and some of the potential candidates for SARS-CoV-2 treatment which are still under clinical studies for their effectiveness against SARS-CoV-2. Overall, it is of high importance to mention that clinical trials are necessary for confirming promising drug candidates and effective vaccines and the safety profile of the new components must be evaluated before translation of in vitro studies for implementation in clinical use.
The Emerging Role of Neuropeptides in Parkinson’s Disease
Authors: Zheng Yanan , Zhang Linlin , Xie Junxia , Shi Limin
Published: March 2021

Parkinson’s disease (PD), the second most common age-related neurodegenerative disease, results from the loss of dopamine neurons in the substantia nigra. This disease is characterized by cardinal non-motor and motor symptoms. Several studies have demonstrated that neuropeptides, such as ghrelin, neuropeptide Y, pituitary adenylate cyclase-activating polypeptide, substance P, and neurotensin, are related to the onset of PD. This review mainly describes the changes in these neuropeptides and their receptors in the substantia nigra-striatum system as well as the other PD-related brain regions. Based on several in vitro and in vivo studies, most neuropeptides play a significant neuroprotective role in PD by preventing caspase-3 activation, decreasing mitochondrial-related oxidative stress, increasing mitochondrial biogenesis, inhibiting microglial activation, and anti-autophagic activity. Thus, neuropeptides may provide a new strategy for PD therapy.
Prevalence and Clinical Features of FOG in Chinese PD Patients, a Multicenter and Cross-Sectional Clinical Study
Authors: Gan Jing , Liu Weiguo , Cao Xuebing , Xie Anmu , Li Wentao , Yuan Canxing , Jin Lirong , Liu Suzhi , Jin Lingjing , Guo Dengjun , Shen Yuefei , Wu Yuncheng , Liu Zhenguo
Published: March 2021

Objectives: Freezing of gait (FOG) is generally considered as an independent symptom of Parkinson's disease (PD) with a complex pathophysiology. There is a wide range of associated clinical features of FOG reported from different studies without consistent conclusion. Thus, a multicenter, cross-sectional study was designed to investigate the prevalence and clinical features of FOG together with its unique contribution quality of life in Chinese PD patients.

Methods: Eight hundred and thirty eight PD patients were consecutively recruited into this study from 12 hospital centers in six provinces in China. Clinical information, including motor and neuropsychological features as well as pharmacological details, was collected.

Results: Of 827 PD patients, 245 (29.63%) reported FOG. The prevalence of FOG was strongly correlated with modified H-Y stages and symptomatic duration (p < 0.01). 84.90% freezers experienced FOG during turning and 88.98% experienced when initiating the first step. Compared with non-freezers, freezers reported longer disease duration (7.73 ± 5.44 vs. 4.69 ± 3.94, p < 0.000), higher frequent PIGD phenotype (61.22 vs. 35.91%, p < 0.000), higher scores of UPDRS III (32.85 ± 15.47 vs. 22.38 ± 12.89, p < 0.000), HAMA (10.99 ± 7.41 vs. 7.59 ± 6.47, p < 0.000), HAMD (15.29 ± 10.29 vs. 10.58 ± 8.97, p < 0.000) and lower MMSE score (25.12 ± 5.27 vs. 26.63 ± 3.97, p < 0.000), and higher daily levodopa dosage (432.65 ± 264.31 vs. 319.19 ± 229.15, p < 0.000) with less frequent initial use of dopaminergic agonist (8.57 vs. 14.78%, p < 0.05). Using binary logistic regression, the associated factors of FOG might be non-tremor dominant onset (OR = 3.817, p < 0.000), the presence of anxiety (OR = 2.048, p < 0.000) and imbalance (OR = 4.320, p = 0.012). Freezers had poorer quality of life than non-freezers and FOG impacted PDQ-8 independently.

Conclusion: Nearly one third of the PD patients experienced FOG. Its frequency increased with PD progression and FOG reduced independently the quality of life. Non-tremor dominant, disease progression, and anxiety were risk factors of FOG.
Multiple Sclerosis Patient Management During the COVID-19 Pandemic: Practical Recommendations From the Portuguese Multiple Sclerosis Study Group (GEEM)
Authors: Cerqueira João J. , Ladeira Ana F. , Silva Ana M. , Timóteo Ângela , Vale José , Sousa Lívia , Arenga Marta , Abreu Pedro , Guerreiro Rui , de Sá João
Published: March 2021

The spread of the COVID-19 pandemic has imposed significant challenges on healthcare provision, requiring changes in the conventional patient management, particularly in chronic diseases like multiple sclerosis (MS). To increase patient safety and reduce the risk of infection, while ensuring an appropriate and regular follow-up, tele-medicine gained prominence as a valid alternative to face-to-face appointments. However, the urgency of the implementation and the lack of experience in most MS centers led to “ad hoc” and extremely diverse approaches, which now merit to be standardized and refined. Indeed, while tele-consultation cannot fully replace face-to-face visits, it certainly can, and will, be incorporated as part of the routine care of MS patients in the near future. Bearing this in mind, the Portuguese Multiple Sclerosis Study Group (GEEM) has developed a set of recommendations for the usage of tele-medicine in the management of MS patients, both during the pandemic and in the future. The consensus was obtained through a two-step modified Delphi methodology, resulting in 15 recommendations, which are detailed in the manuscript.
Admission Dehydration Is Associated With Significantly Lower In-Hospital Mortality After Intracerebral Hemorrhage
Authors: Gao Bin , Gu Hongqiu , Yu Wengui , Liu Shimeng , Zhou Qi , Kang Kaijiang , Zhang Jia , Li Zixiao , Zhao Xingquan , Wang Yongjun
Published: March 2021

Background and Purpose: Our aim was to investigate the frequency of dehydration at admission and associations with in-hospital mortality in patients with intracerebral hemorrhage (ICH).

Methods: Data of consecutive patients with ICH between August 2015 and July 2019 from the China Stroke Center Alliance (CSCA) registry were analyzed. The patients were stratified based on the blood urea nitrogen (BUN) to creatinine (CR) ratio (BUN/CR) on admission into dehydrated (BUN/CR ≥ 15) or non-dehydrated (BUN/CR < 15) groups. Data were analyzed with multivariate logistic regression models to investigate admission dehydration status and the risks of death at hospital.

Results: A total number of 84,043 patients with ICH were included in the study. The median age of patients on admission was 63.0 years, and 37.5% of them were women. Based on the baseline BUN/CR, 59,153 (70.4%) patients were classified into dehydration group. Patients with admission dehydration (BUN/CR ≥ 15) had 13% lower risks of in-hospital mortality than those without dehydration (BUN/CR < 15, adjusted OR = 0.87, 95%CI 0.78–0.96). In patients aged <65 years, admission dehydration was associated with 19% lower risks of in-hospital mortality (adjusted OR = 0.81, 95%CI 0.70–0.94. adjusted p = 0.0049) than non-dehydrated patients.

Conclusion: Admission dehydration is associated with significantly lower in-hospital mortality after ICH, in particular, in patients <65 years old.
A Novel Recurrent Neural Network to Classify EEG Signals for Customers' Decision-Making Behavior Prediction in Brand Extension Scenario
Authors: Ma Qingguo , Wang Manlin , Hu Linfeng , Zhang Linanzi , Hua Zhongling
Published: March 2021

It was meaningful to predict the customers' decision-making behavior in the field of market. However, due to individual differences and complex, non-linear natures of the electroencephalogram (EEG) signals, it was hard to classify the EEG signals and to predict customers' decisions by using traditional classification methods. To solve the aforementioned problems, a recurrent t-distributed stochastic neighbor embedding (t-SNE) neural network was proposed in current study to classify the EEG signals in the designed brand extension paradigm and to predict the participants' decisions (whether to accept the brand extension or not). The recurrent t-SNE neural network contained two steps. In the first step, t-SNE algorithm was performed to extract features from EEG signals. Second, a recurrent neural network with long short-term memory (LSTM) layer, fully connected layer, and SoftMax layer was established to train the features, classify the EEG signals, as well as predict the cognitive performance. The proposed network could give a good prediction with accuracy around 87%. Its superior in prediction accuracy as compared to a recurrent principal component analysis (PCA) network, a recurrent independent component correlation algorithm [independent component analysis (ICA)] network, a t-SNE support vector machine (SVM) network, a t-SNE back propagation (BP) neural network, a deep LSTM neural network, and a convolutional neural network were also demonstrated. Moreover, the performance of the proposed network with different activated channels were also investigated and compared. The results showed that the proposed network could make a relatively good prediction with only 16 channels. The proposed network would become a potentially useful tool to help a company in making marketing decisions and to help uncover the neural mechanisms behind individuals' decision-making behavior with low cost and high efficiency.
Role of Muscle Mass and Nutritional Assessment Tools in Evaluating the Nutritional Status of Patients With Locally Advanced Nasopharyngeal Carcinoma
Authors: Pan Xi , Liu Hong , Feng Guo , Xiao Jie , Wang Meng , Liu Hua , Xie Xueyi , Rong Zhipeng , Wu Jinru , Liu Min
Published: March 2021

Objective: This study was to explore the role and necessity of muscle mass [fat-free mass index (FFMI) and appendicular skeletal muscle index (ASMI) measured by bioelectrical impedance analysis (BIA)] in nutritional status evaluation of patients with locally advanced (III, IVa) nasopharyngeal carcinoma (NPC).

Methods: One hundred and thirty locally advanced NPC patients were recruited. Their nutritional status was assessed by albumin (ALB), body mass index (BMI), Nutritional Risk Screening 2002 (NRS 2002), Patient generated-Subjective Global Assessment (PG-SGA), and muscle mass. Consistency test and McNemar test were used to evaluate the consistency of muscle mass with ALB, BMI, NRS 2002, and PG-SGA, and correlation analysis was performed on muscle mass and PG-SGA or BMI.

Results: 61/130 (46.9%) of the patients had nutritional risks according to NRS 2002, 68/130 (53.1%) of the patients had malnutrition according to PG-SGA assessment. FFMI and ASMI could determine the loss of muscle mass that cannot be detected by albumin (30.2 and 65.6%), BMI (28.0 and 35.3%), NRS 2002 (26.1 and 25.0%), and PG-SGA (18.6 and 55.6%). McNemar test showed that the malnutrition results assessed by FFMI and BMI were inconsistent (P <0.001), but further Pearson correlation analysis showed that BMI was positively correlated with FFMI (rs = 0.300, P = 0.001).

Conclusion: The commonly used nutritional assessment scale/parameters cannot identify the muscle mass loss in patients with locally advanced NPC. Analysis of human body composition is important for nutritional assessment in patients with locally advanced NPC.
High Expression of Hyaluronan-Mediated Motility Receptor Predicts Adverse Outcomes: A Potential Therapeutic Target for Head and Neck Squamous Cell Carcinoma
Authors: Lu Tianzhu , Zheng Yahan , Gong Xiaochang , Lv Qiaoli , Chen Junjun , Tu Ziwei , Lin Shaojun , Pan Jianji , Guo Qiaojuan , Li Jingao
Published: March 2021

Background:Several studies have shown that the hyaluronan-mediated motility receptor (HMMR) is overexpressed in various cancers and could be a potential prognostic factor. However, further research is still required to determine the prognostic value and potential function of HMMR in head and neck squamous cell carcinoma (HNSCC).

Materials and Methods:Transcriptomic expression data were collected from the Cancer Genome Atlas database (TCGA) and Gene Expression Omnibus and the differences in HMMR expression between normal and tumor tissues were analyzed. The correlation between the methylation level of HMMR and its mRNA expression was analyzed via cBioPortal. Additionally, the data obtained from TCGA was analyzed with MethSurv to determine the prognostic value of the HMMR methylation levels in HNSCC. Gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA) were used to explore the potential biological functions of HMMR.

Results:HMMR was highly expressed in HNSCC tumor tissue compared to normal tissue (p< 0.001). Multivariate analysis (MAV) showed that high HMMR mRNA expression was an independent prognostic factor of overall survival (OS) in TCGA (HR = 1.628, 95% CI: 1.169–2.266,p= 0.004) and GSE41613 data (HR = 2.238,p= 0.013). The methylation level of HMMR negatively correlated with the HMMR expression (R= −0.12,p< 0.001), and patients with low HMMR methylation had worse OS than patients with high methylation (p< 0.001). GSEA found that HMMR expression was associated with the KARS, EMT, and G2M checkpoint pathways, as well as the interferon-gamma and interferon-alpha responses, whereas ssGSEA showed thatHMMRexpression positively correlated with the infiltration level of Th2 cells. MAV confirmed that high HMMR protein expression was an inferior independent factor for OS (HR = 2.288,p= 0.045) and progression-free survival (HR = 2.247,p= 0.038) in 70 HNSCC.

Conclusions:This study demonstrated that the upregulation of HMMR mRNA and protein in HNSCC is a biomarker for poor prognosis. The biological functions of HMMR are potentially related to the KARS, EMT, and G2M checkpoint pathways, as well as the interferon-gamma and interferon-alpha responses. These findings help to elucidate the role of HMMR in carcinogenesis and lay a foundation for further study.
Clinical Features and Prognoses of IgG4-Positive and IgG4-Negative Lacrimal Lymphomas
Authors: Liu Rui , Wang Jinjin , Wang Nan , Li Jing , Ge Xin , Zhang Jingxue , Ma Jianmin
Published: March 2021

Purpose: The clinical characteristics and prognoses of immunoglobulin G4-positive (IgG4+) and IgG4-negative (IgG4−) lacrimal lymphomas were comparatively analyzed to screen for clinical indicators with differential diagnostic significance.

Methods: This was a retrospective and single-center clinical study. From June 2011 to June 2018, clinical data of 39 patients with lacrimal lymphoma, diagnosed by histopathology were collected from the Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University.

Results: According to inclusion and exclusion criteria, 30 (76.9%) were in the IgG4− group and 9 (23.1%) were in the IgG4+ group. In the IgG4+ group, the sex ratio of male to female was 2:1 and the mean age was 56.67 ± 13.29 years old. In the IgG4− group, the sex ratio of male to female was 3.29:1 and the mean age was 61.47 ± 12.87 years old. Statistical analysis of the clinical indicators showed significant differences between the two groups in affected eye, preoperative history of glucocorticoids, ocular nerve thickening, the expression of serum IgG4 and prognosis (P < 0.05). There was no significant statistical difference in laboratory indicators between the two groups, including C3, C4, RF, ASO, CRP, IgA, IgM, IgG, IgG1, IgG2, and IgG3 (P > 0.05). The event-free cumulative percentages at 3 and 5 years for the 39 lacrimal lymphomas were 81.1 and 62.4%, respectively, with recurrence and death as end events. In 34 lacrimal gland MALT lymphoma cases, the event-free cumulative percentages at 3 and 5 years were 84.4 and 69.1%, respectively. In the IgG4+ and IgG4− groups, the event-free cumulative percentages at 3 years were 75.0 and 87.7%, respectively. The event-free cumulative percentage at 5 years was 62.6% in the IgG4-group and insignificant in the IgG4+ group. There was no statistical difference in event-free cumulative percentage between the two groups (P = 0.983).

Conclusion: The pathogenesis and disease characteristics of IgG4-positive lacrimal lymphoma may differ from IgG4-negative lacrimal lymphoma, but the positive expression of IgG4 may not have significant influence on the recurrence of lacrimal lymphoma.
Technical Challenges of Real-Time Adaptive MR-Guided Radiotherapy
Authors: Thorwarth Daniela , Low Daniel A.
Published: March 2021

In the past few years, radiotherapy (RT) has experienced a major technological innovation with the development of hybrid machines combining magnetic resonance (MR) imaging and linear accelerators. This new technology for MR-guided cancer treatment has the potential to revolutionize the field of adaptive RT due to the opportunity to provide high-resolution, real-time MR imaging before and during treatment application. However, from a technical point of view, several challenges remain which need to be tackled to ensure safe and robust real-time adaptive MR-guided RT delivery. In this manuscript, several technical challenges to MR-guided RT are discussed. Starting with magnetic field strength tradeoffs, the potential and limitations for purely MR-based RT workflows are discussed. Furthermore, the current status of real-time 3D MR imaging and its potential for real-time RT are summarized. Finally, the potential of quantitative MR imaging for future biological RT adaptation is highlighted.
Beginning Restorative Activities Very Early: Implementation of an Early Mobility Initiative in a Pediatric Onco-Critical Care Unit
Authors: Ghafoor Saad , Fan Kimberly , Williams Sarah , Brown Amanda , Bowman Sarah , Pettit Kenneth L. , Gorantla Shilpa , Quillivan Rebecca , Schwartzberg Sarah , Curry Amanda , Parkhurst Lucy , James Marshay , Smith Jennifer , Canavera Kristin , Elliott Andrew , Frett Michael , Trone Deni , Butrum-Sullivan Jacqueline , Barger Cynthia , Lorino Mary , Mazur Jennifer , Dodson Mandi , Melancon Morgan , Hall Leigh Anne , Rains Jason , Avent Yvonne , Burlison Jonathan , Wang Fang , Pan Haitao , Lenk Mary Anne , Morrison R. Ray , Kudchadkar Sapna R.
Published: March 2021

Introduction

Children with underlying oncologic and hematologic diseases who require critical care services have unique risk factors for developing functional impairments from pediatric post-intensive care syndrome (PICS-p). Early mobilization and rehabilitation programs offer a promising approach for mitigating the effects of PICS-p in oncology patients but have not yet been studied in this high-risk population.

Methods

We describe the development and feasibility of implementing an early mobility quality improvement initiative in a dedicated pediatric onco-critical care unit. Our primary outcomes include the percentage of patients with consults for rehabilitation services within 72 h of admission, the percentage of patients who are mobilized within 72 h of admission, and the percentage of patients with a positive delirium screen after 48 h of admission.

Results

Between January 2019 and June 2020, we significantly increased the proportion of patients with consults ordered for rehabilitation services within 72 h of admission from 25 to 56% (p<0.001), increased the percentage of patients who were mobilized within 72 h of admission to the intensive care unit from 21 to 30% (p=0.02), and observed a decrease in patients with positive delirium screens from 43 to 37% (p=0.46). The early mobility initiative was not associated with an increase in unplanned extubations, unintentional removal of central venous catheters, or injury to patient or staff.

Conclusions

Our experience supports the safety and feasibility of early mobility initiatives in pediatric onco-critical care. Additional evaluation is needed to determine the effects of early mobilization on patient outcomes.