bluuebunny/crossref_metadata_2025 huggingface dataset:
Composition and Diversity of the Ocular Surface Microbiota in Patients With Blepharitis in Northwestern China
Authors: Wang Changhao , Dou Xiuhong , Li Jian , Wu Jie , Cheng Yan , An Na
Published: December 2021

Purpose: To investigate the composition and diversity of the microbiota on the ocular surface of patients with blepharitis in northwestern China via 16S rDNA amplicon sequencing.

Methods: Thirty-seven patients with blepharitis divided into groups of anterior, posterior and mixed blepharitis and twenty healthy controls from northwestern China were enrolled in the study. Samples were collected from the eyelid margin and conjunctival sac of each participant. The V3–V4 region of bacterial 16S rDNA in each sample was amplified and sequenced on the Illumina HiSeq 2500 sequencing platform, and the differences in taxonomy and diversity among different groups were compared.

Results: The composition of the ocular surface microbiota of patients with blepharitis was similar to that of healthy subjects, but there were differences in the relative abundance of each bacterium. At the phylum level, the abundances of Actinobacteria, Cyanobacteria, Verrucomicrobia, Acidobacteria, Chloroflexi, and Atribacteria were significantly higher in the blepharitis group than in the healthy control group, while the relative abundance of Firmicutes was significantly lower (p < 0.05, Mann-Whitney U). At the genus level, the abundances of Lactobacillus, Ralstonia, Bacteroides, Akkermansia, Bifidobacterium, Escherichia-Shigella, Faecalibacterium, and Brevibacterium were significantly higher in the blepharitis group than in the healthy control group, while the relative abundances of Bacillus, Staphylococcus, Streptococcus, and Acinetobacter were significantly lower in the blepharitis group (p < 0.05, Mann-Whitney U). The microbiota of anterior blepharitis was similar to that of mixed blepharitis but different from that of posterior blepharitis. Lactobacillus and Bifidobacterium are biomarkers of posterior blepharitis, and Ralstonia is a biomarker of mixed blepharitis. There was no significant difference in the ocular surface microbiota between the eyelid margin and conjunctival sac with or without blepharitis.

Conclusion: The ocular surface microbiota of patients with blepharitis varied among different study groups, according to 16S rDNA amplicon sequencing analysis. The reason might be due to the participants being from different environments and having different lifestyles. Lactobacillus, Bifidobacterium, Akkermansia, Ralstonia, and Bacteroides may play important roles in the pathogenesis of blepharitis.
Differential Survivability of Two Genetically Similar Salmonella Thompson Strains on Pre-harvest Sweet Basil (Ocimum basilicum) Leaves
Authors: Zwe Ye Htut , Ten Michelle Mei Zhen , Pang Xinyi , Wong Chun Hong , Li Dan
Published: December 2021

Although conventionally considered an animal pathogen, recent evidence increasingly suggests that fresh produce may act as significant transmission vehicles and alternative hosts to Salmonella. This study reports the differential survivability of two genetically similar Salmonella Thompson strains (ST 889B and ST 688C) on the adaxial surface of pre-harvest basil (Ocimum basilicum) leaves. Upon inoculation, two distinct phenomena, a dried water-print or a macroscopic lesion, were observed within 24 h. ST 889B survived better than ST 688C on healthy-looking leaves without lesions, possibly due to its higher biofilm-forming ability. Both strains survived better on the leaves with lesions than on the healthy-looking leaves (ST 688C: 4.39 ± 0.68 vs. 2.18 ± 0.29; ST 889B: 4.78 ± 0.12 vs. 2.83 ± 0.18 log CFU per sample at 6 days post-inoculation). ST 889B caused the formation of lesions at a higher frequency [70/117 leaves (59.8%)] than ST 688C [35/96 leaves (36.5%)]. Thus, we highlighted two distinct Salmonella survival strategies in the basil pathosystem and demonstrated gene expression polymorphism (variations in the expression of the same set of genes) as an indispensable strategy in the colonization of plants as hosts by the human pathogens.
The Coexistence Relationship Between Plants and Soil Bacteria Based on Interdomain Ecological Network Analysis
Authors: Cong Wei , Yu Jingjing , Feng Kai , Deng Ye , Zhang Yuguang
Published: December 2021

The relationship between plants and their associated soil microbial communities plays a crucial role in maintaining ecosystem processes and function. However, identifying these complex relationships is challenging. In this study, we constructed an interdomain ecology network (IDEN) of plant–bacteria based on SparCC pairwise associations using synchronous aboveground plant surveys and belowground microbial 16S rRNA sequencing among four different natural forest types along the climate zones in China. The results found that a total of 48 plants were associated with soil bacteria among these four sites, and soil microbial group associations with specific plant species existed within the observed plant–bacteria coexistence network. Only 0.54% of operational taxonomy units (OTUs) was shared by the four sites, and the proportion of unique OTUs for each site ranged from 43.08 to 76.28%, which occupied a large proportion of soil bacterial community composition. The plant–bacteria network had a distinct modular structure (p < 0.001). The tree Acer tetramerum was identified as the network hubs in the warm temperate coniferous and broad-leaved mixed forests coexistence network and indicates that it may play a key role in stabilizing of the community structure of these forest ecosystems. Therefore, IDEN of plant–bacteria provides a novel perspective for exploring the relationships of interdomain species, and this study provides valuable insights into understanding coexistence between above-ground plants and below-ground microorganisms.
Captivity Influences the Gut Microbiome of Rhinopithecus roxellana
Authors: Wang Xiaochen , Wang Ziming , Pan Huijuan , Qi Jiwei , Li Dayong , Zhang Liye , Shen Ying , Xiang Zuofu , Li Ming
Published: December 2021

Ex situ(captivity in zoos) is regarded as an important form of conservation for endangered animals. Many studies have compared differences in the gut microbiome between captive and wild animals, but few have explained those differences at the functional level due to the limited amount of 16S rRNA data. Here, we compared the gut microbiome of captive and wildRhinopithecus roxellana, whose high degree of dietary specificity makes it a good subject to observe the effects of the captive environment on their gut microbiome, by performing a metagenome-wide association study (MWAS). The Chao1 index was significantly higher in the captiveR. roxellanacohort than in the wild cohort, and the Shannon index of captiveR. roxellanawas higher than that of the wild cohort but the difference was not significant. A significantly increased ratio ofPrevotella/Bacteroides, which revealed an increased ability to digest simple carbohydrates, was found in the captive cohort. A significant decrease in the abundance of Firmicutes and enrichment of genes related to the pentose phosphate pathway were noted in the captive cohort, indicating a decreased ability of captive monkeys to digest fiber. Additionally, genes required for glutamate biosynthesis were also significantly more abundant in the captive cohort than in the wild cohort. These changes in the gut microbiome correspond to changes in the composition of the diet in captive animals, which has more simple carbohydrates and less crude fiber and protein than the diet of the wild animals. In addition, more unique bacteria in captiveR. roxellanawere involved in antibiotic resistance (Acinetobacter) and diarrhea (Desulfovibrio piger), and in the prevention of diarrhea (Phascolarctobacterium succinatutens) caused byClostridioides difficile. Accordingly, our data reveal the cause-and-effect relationships between changes in the exact dietary composition and changes in the gut microbiome on both the structural and functional levels by comparing of captive and wildR. roxellana.
The Evaluation of Cellular Immunity to Avian Viral Diseases: Methods, Applications, and Challenges
Authors: Hao Xiaoli , Zhang Fan , Yang Yi , Shang Shaobin
Published: December 2021

Cellular immune responses play critical roles in the control of viral infection. However, the immune protection against avian viral diseases (AVDs), a major challenge to poultry industry, is yet mainly evaluated by measuring humoral immune response though antibody-independent immune protection was increasingly evident in the development of vaccines against some of these diseases. The evaluation of cellular immune response to avian viral infection has long been neglected due to limited reagents and methods. Recently, with the availability of more immunological reagents and validated approaches, the evaluation of cellular immunity has become feasible and necessary for AVD. Herein, we reviewed the methods used for evaluating T cell immunity in chickens following infection or vaccination, which are involved in the definition of different cellular subset, the analysis of T cell activation, proliferation and cytokine secretion, andin vitroculture of antigen-presenting cells (APC) and T cells. The pros and cons of each method were discussed, and potential future directions to enhance the studies of avian cellular immunity were suggested. The methodological improvement and standardization in analyzing cellular immune response in birds after viral infection or vaccination would facilitate the dissection of mechanism of immune protection and the development of novel vaccines and therapeutics against AVD.
Barriers to Optimal Acute Management of Stroke: Perspective of a Stroke Center in Mexico City
Authors: Cano-Nigenda Vanessa , Castellanos-Pedroza Enrique , Manrique-Otero Diana , Méndez Beatriz , Menéndez-Manjarrez María Fernanda , Toledo-Treviño Roberto , Calderón Miguel , Arauz Antonio
Published: December 2021

Background: Stroke is a leading cause of death and disability worldwide, particularly in low- and middle-income countries. We aimed to identify the main barriers to optimal acute management of stroke in a referral center.

Methods: Demographic data was collected from patients assessed with acute stroke in the emergency department of the Instituto Nacional de Neurología y Neurocirugía (INNN) from January to June 2019. Additionally, a telephone interview was conducted with patients/primary caregiver to know which they considered the main reason for the delay in arrival at INNN since the onset of stroke.

Results: 116 patients were assessed [age 65 ± 15 years, 67 (57.8%) men]. Patients consulted other facilities prior to arrival at INNN in 59 (50.9%) cases (range of hospitals visited 1–4), 83 (71.6%) arrived in a private car, with prenotification in only 4 (3.4%) of the total sample. The mean onset-to-door time was 17 h (45 min−10 days). Telephone interviews were done in 61 patients/primary caregivers, stating that they consider the multiple evaluations in other facilities [n = 26/61 (42.6%)] as the main reason for delay in arrival at the ED, followed by ignorance of stroke symptoms and treatment urgency [n = 21/61 (34.4%)].

Conclusion: In this small, retrospective, single center study, the main prehospital barrier to optimal acute management of stroke in a developing country is multiple medical evaluations prior to the patient's transport to a specialized stroke hospital, who mostly arrived in a private car and without prenotification. These barriers can be overcome by strengthening public education and improving patient transfer networks and telemedicine.
Frequency-Specific Blood Oxygen Level Dependent Oscillations Associated With Pain Relief From Ankle Acupuncture in Patients With Chronic Low Back Pain
Authors: Xiang Anfeng , Chen Meiyu , Qin Chuan , Rong Jun , Wang Can , Shen Xueyong , Liu Sheng
Published: December 2021

Objective: Recent advances in brain imaging have deepened our knowledge of the neural activity in distinct brain areas associated with acupuncture analgesia. However, there has not been conclusive research into the frequency-specific resting-state functional changes associated with acupuncture analgesia in patients with chronic pain. Here, we aimed to characterize changes across multiple frequencies of resting-state cortical activity associated with ankle acupuncture stimulation (AAS) in patients with chronic low back pain (CLBP) and healthy controls.

Methods: Twenty seven patients with CLBP and Twenty five age- and gender-matched healthy volunteers were enrolled in the study. Participants received tactile sham acupuncture (TSA) and AAS, respectively. The whole-brain amplitude of low-frequency fluctuation (ALFF) in the range 0.01–0.25 Hz was assessed for changes associated with each intervention. Further, a visual analog scale (VAS) was used to collect subjective measures of pain intensity in patients. Linear mixed-effect modeling (LME) was used to examine the mean ALFF values of AAS and TSA between patients and healthy controls.

Results: The ALFF was modulated in the default mode network (an increase in the medial prefrontal cortex, and a decrease in the cerebellum/posterior ingulate/parahippocampus, P < 0.01, corrected) in both patients and controls. Decreased ALFF in the bilateral insular was frequency-dependent. Modulations in the cerebellum and right insular were significantly correlated with VAS pain score after AAS (P < 0.01).

Conclusion: Hence, frequency-specific resting-state activity in the cerebellum and insular was correlated to AAS analgesia. Our frequency-specific analysis of ALFF may provide novel insights related to pain relief from acupuncture.
Gut Microbiota Composition and Predicted Microbial Metabolic Pathways of Obesity Prone and Obesity Resistant Outbred Sprague-Dawley CD Rats May Account for Differences in Their Phenotype
Authors: Obanda Diana N. , Keenan Michael J. , Page Ryan , Raggio Anne M. , Taylor Christopher M. , Marx Brian D. , Stout Rhett W. , Guice Justin , Luo Meng , Welsh David A. , Coulon Diana , Husseneder Claudia
Published: December 2021

Like humans, outbred Sprague-Dawley CD rats exhibit a polygenic pattern of inheritance of the obese phenotype and not all individuals exposed to a high calorie intake develop obesity. We hypothesized that differences in gut microbiota composition account for phenotype differences between obese prone (OP) and obese resistant (OR) rats. We studied the gut microbiota composition of OPand OR rats after a high fat (HF) diet and how they respond to fermentation of resistant starch (RS). In phase 1 of the study 28 OP and 28 OR rats were fed a HF diet. In order to determine causal role of microbiota on phenotypes, In phase 2, a microbiota transplant between the two phenotypes was performed before switching all rats to a HF diet supplemented with 20% RS. We determined microbiota composition by 16S sequencing and predicted microbiota function by PICRUSt2. Despite a similar calorie intake, in phase 2 OP rats gained more weight and accumulated more abdominal fat in both phase 1 and 2 compared to OR rats (P < 0.001; n = 6). The OP rats fermented RS more robustly compared with OR rats with an increase in total bacteria, short chain fatty acids, and increased weight of the cecum, but microbiota of OP rats had much lower alpha diversity and evenness. The microbiota of OP rats, had higher amounts of bacteria from order Bacteroidales, specifically family Muribaculaceae (S24-7), which is known to possess several starch degrading enzymes and was reported in previous studies to increase with fermentation of RS. The OR rats fermented RS less but had higher bacterial diversity and evenness and had significantly higher bacterial counts from phylum Firmicutes particularly order Clostridiales, genus Clostridium and an uncultured bacterium of the genus Akkermansia. The microbiota of OR rats had enhanced bacterial chemotaxis, phosphotransferase system (PTS), and fatty acid biosynthesis compared to OP rats whose microbiota had higher glycan degradation and LPS biosynthesis pathways. The microbiota transplant did not change obesity phenotype or microbiota composition. In conclusion, a higher alpha-diversity and evenness of the microbiota and higher proportions of Clostridiales and Akkermansia in OR rats were associated with a better metabolic phenotype with lower body fat. However, robust RS fermentation caused a lower diversity and evenness and did not result in a leaner phenotype.
Relative Rates of Gluten Digestion by Nine Commercial Dietary Digestive Supplements
Authors: Tanner Gregory John
Published: December 2021

Endopeptidases containing supplements may digest gluten and reduce the impact on celiac and gluten-sensitive subjects who inadvertently consume gluten. We investigated the relative rate of disappearance of coeliac relevant epitopes in extracts of nine commercial supplements, using two competitive enzyme-linked immunosorbent assays (ELISAs)—Ridascreen (detects QQPFP, QQQFP, LQPFP, and QLPFP) and Gluten-Tec (detects Glia-α20 and PFRPQQPYPQ). All epitopes are destroyed by cleavage after P and Q amino acids. Rates at pH 3.5 and pH 7.0 were measured. These experiments were designed to measure relative rates of epitope digestion not to mimic in vivo digestion. The supplements were: 1 GluteGuard, 2 GlutenBlock, 3 GliadinX, 4 GlutnGo, 5 GlutenRescue, 6 Eat E-Z Gluten+, 7 Glutenease, 8 Glutezyme, and 9 Gluten Digest. The mean initial rate and half-lives of epitope digestion were deduced and extrapolated to rates at the recommended dose of one supplement in a fasting stomach volume. At pH 7, supplement 1 was the fastest acting of the supplements, with Ridascreen ELISA, more than twice as fast as the next fastest supplements, 5, 6, 7, and 8. Supplements 2, 3, and 4 showed little activity at pH 7.0. Supplement 1 was also the fastest acting at pH 7 with Gluten-Tec ELISA, more than three times the rate for supplements 2 and 3, with supplements 4–9 showing minimal activity. At pH 3.5, supplement 1 acted more than five times as fast as the next fastest supplements, 2 and 3, when measured by Ridascreen, but supplements 2 and 3 were over two times faster than supplement 1 when measured by Gluten-Tec. Supplements 4–9 demonstrated minimal activity at pH 3.5 with either ELISA. Supplement 1 most rapidly digested the key immuno-reactive gluten epitopes identified by the R5 antibody in the Codex-approved competitive Ridascreen ELISA method and associated with the pathology of celiac disease.
A Functional Variant in SEPP1 Interacts With Plasma Selenium Concentrations on 3-Year Lipid Changes: A Prospective Cohort Study
Authors: Zhou Li , Liang Xiaoling , Xie Manling , Yin Jiawei , Huang Yue , Li Xiaoqin , Shan Zhilei , Chen Liangkai , Zhang Yan , Luo Cheng , Liu Liegang
Published: December 2021

Background: Excess selenium has been related with adverse lipid levels in previous epidemiological studies. Meanwhile, a functional variant in SEPP1 (encodes selenoprotein P), namely rs7579, has been suggested to modulate lipid metabolism. However, the interactions between selenium status and rs7579 polymorphism on lipid changes remain unclear.

Objective: To examine whether the associations between plasma selenium and 3-year lipid changes is modified by rs7579 polymorphism.

Methods: A prospective cohort study was conducted among 1,621 individuals to examine the associations between baseline plasma selenium and 3-year lipid changes, as well as the interactions between plasma selenium and rs7579 polymorphism on lipid changes.

Results: The median (interquartile range) concentration of plasma selenium was 91.68 (81.55–104.92) μg/L. Higher plasma selenium was associated with adverse 3-year lipid changes. Comparing the highest to the lowest quartiles of plasma selenium concentrations, 3-year lipid changes were elevated by 8.25% (95% CI: 1.54–14.96%) for triglycerides (P = 0.016), 5.88% (3.13–8.63%) for total cholesterol (P < 0.001), 7.37% (3.07–11.67%) for low-density lipoprotein cholesterol (P = 0.0008), 6.44% (2.66–10.21%) for non-high-density lipoprotein cholesterol (P = 0.0009), 4.99% (0.62–9.36%) for total cholesterol/high-density lipoprotein cholesterol ratio (P = 0.025), and 7.00% (1.55–12.46%) for low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (P = 0.012). In analyses stratified by rs7579 genotypes, positive associations between plasma selenium concentrations and 3-year changes in triglycerides, TC, LDL-C, non-HDL-C, TC/HDL-C ratio, and LDL-C/HDL-C ratio were observed among CC genotype carriers, but negative associations between plasma selenium and TC/HDL-C ratio, and LDL-C/HDL-C ratio were observed among TT genotype carriers.

Conclusions: Our findings suggested that plasma selenium was associated with 3-year lipid changes differentially by rs7579 genotypes, and higher plasma selenium was associated with adverse lipid changes among rs7579 CC genotype carriers, but not among T allele carriers.
Current Surgical Therapy of Locally Advanced cSCC: From Patient Selection to Microsurgical Tissue Transplant. Review
Authors: Brambullo Tito , Azzena Gian Paolo , Toninello Paolo , Masciopinto Giuseppe , De Lazzari Alberto , Biffoli Bernardo , Vindigni Vincenzo , Bassetto Franco
Published: December 2021

Among the non-melanoma skin cancers (NMSC) the squamous cell carcinoma (SCC) is one of the most challenging for the surgeon. Local aggressiveness and a tendency to metastasize to regional lymph nodes characterize the biologic behavior. The variants locally advanced and metastatic require wide excision and node dissection. Such procedures can be extremely detrimental for patients. The limit of the surgery can be safely pushed forward with a multidisciplinary approach. The concept of skin oncoplastic surgery, the ablative procedures and the reconstructive options (skin graft, pedicled flap, microsurgical free flap) are discussed together with a literature review.
Photodynamic and Photothermal Therapy of Hepatocellular Carcinoma
Authors: Fan Zhe , Zhuang Chengjun , Wang Shuang , Zhang Yewei
Published: December 2021

Hepatocellular carcinoma (HCC) is the most common primary liver tumor. It is ranked the sixth most common neoplasm and the third most common cause of cancer mortality. At present, the most common treatment for HCC is surgery, but the 5-year recurrence rates are still high. Patients with early stage HCC with few nodules can be treated with resection or radiofrequency ablation (RFA); while for multinodular HCC, transarterial chemoembolization (TACE) has been the first-line treatment. In recent years, based on medical engineering cooperation, nanotechnology has been increasingly applied to the treatment of cancer. Photodynamic therapy and photothermal therapy are effective for cancer. This paper summarizes the latest progress of photodynamic therapy and photothermal therapy for HCC, with the aim of providing new ideas for the treatment of HCC.
Role of Three-Dimensional Visualization Modalities in Medical Education
Authors: Bui Ivy , Bhattacharya Arunabh , Wong Si Hui , Singh Harinder R. , Agarwal Arpit
Published: December 2021

For the past two decades, slide-based presentation has been the method of content delivery in medical education. In recent years, other teaching modalities involving three-dimensional (3D) visualization such as 3D printed anatomical models, virtual reality (VR), and augmented reality (AR) have been explored to augment the education experience. This review article will analyze the use of slide-based presentation, 3D printed anatomical models, AR, and VR technologies in medical education, including their benefits and limitations.
Beneficial Effect of Phenytoin and Carbamazepine on GFAP Gene Expression and Mutant GFAP Folding in a Cellular Model of Alexander’s Disease
Authors: Bachetti Tiziana , Zanni Eleonora Di , Adamo Annalisa , Rosamilia Francesca , Sechi M. Margherita , Solla Paolo , Bozzo Matteo , Ceccherini Isabella , Sechi GianPietro
Published: December 2021

Alexander’s disease (AxD) is a rare, usually relentlessly progressive disorder of astroglial cells in the central nervous system related to mutations in the gene encoding the type III intermediate filament protein, glial fibrillary acidic protein (GFAP). The pathophysiology of AxD is only partially understood. Available data indicate that an excessive GFAP gene expression may play a role. In particular, a “threshold hypothesis” has been reported, suggesting that mutant GFAP representing about 20% of the total cellular GFAP should be sufficient to cause disease. Thus, strategies based on reducing cellular mutant GFAP protein levels and/or activating biological processes involved in the correct protein folding could be effective in counteracting the toxic effect of misfolded GFAP. Considering that clomipramine (CLM), which has been selected by a wide small molecules screening as the greatest inhibitory potential drug against GFAP expression, is contraindicated because of its proconvulsant activity in the infantile form of AxD, which is also characterized by the occurrence of epileptic seizures, two powerful antiepileptic agents, carbamazepine (CBZ) and phenytoin (PHT), which share specific stereochemical features in common with CLM, were taken into consideration in a reliable in vitro model of AxD. In the present work, we document for the first time that CBZ and PHT have a definite inhibitory effect on pathological GFAP cellular expression and folding. Moreover, we confirm previous results of a similar beneficial effect of CLM. In addition, we have demonstrated that CBZ and CLM play a refolding effect on mutant GFAP proteins, likely ascribed at the induction of CRYAB expression, resulting in the decrease of mutant GFAP aggregates formation. As CBZ and PHT are currently approved for use in humans, their documented effects on pathological GFAP cellular expression and folding may indicate a potential therapeutic role as disease-modifying agents of these drugs in the clinical management of AxD, particularly in AxD patients with focal epilepsy with and without secondary generalization.
Association of Direct Oral Anticoagulants (DOACs) and Warfarin With Haemorrhagic Risk by Applying Correspondence Analysis to Data From the Italian Pharmacovigilance Database – A Case Study
Authors: Gaio Mario , Ferrajolo Carmen , Zinzi Alessia , Riccardi Consiglia , Di Filippo Pasquale , Carangelo Ludovica , Pieretti Gorizio , Rossi Francesco , Nicoletti Giovanni Francesco , Capuano Annalisa
Published: December 2021

Introduction: Post-marketing data on the risks associated with direct oral anticoagulants (DOACs) are conflicting and only few studies evaluated a comparison between each different DOAC. Real-world data from pharmacovigilance databases can help to better define the safety profile of each DOAC and warfarin. However, Correspondence Analysis (CA) could represent a useful tool in this context.

Objective: In the attempt to assess the usefulness of CA as a signal detection pharmacovigilance tool, we applied this method to the Italian Pharmacovigilance Database (RNF, Rete Nazionale di Farmacovigilanza), by comparing with disproportionality analysis on warfarin and DOACs.

Methods: Study based on AEs sent to RNF by Campania Region from 2008 to 2021, in which warfarin, dabigatran, apixaban, edoxaban or rivaroxaban were reported as suspected drug. AEs were clustered into three Standardized MedDRA Queries (SMQs): Central Nervous System Haemorrhages and Conditions (CNSH), GastroIntestinal Perforation, Ulceration, Obstruction or Haemorrhages (GIPUOH) and other Haemorrhages (HH). Non-haemorrhagic AEs were included in a fourth cluster (nHH).

Results: We retrieved 1,161 reports: 41.5% are associated to warfarin, 21.0% to dabigatran, 17.8% to rivaroxaban, 13.9% to apixaban and 5.8% to edoxaban. No significant differences in age distribution were observed. Results of CA showed that dabigatran and warfarin have the highest contribution (44.910 and 47.656, respectively) to the inertia of Dimension 1 as well as apixaban and dabigatran to the inertia of Dimension 2 (53.768 and 30.488, respectively). Edoxaban and rivaroxaban showed a negligible total contribution. CA biplot showed positive associations between warfarin and HH, apixaban and CNSH and dabigatran and nHH.

Conclusion: Results seem to confirm that DOACs are not interchangeable. Apixaban was surprisingly associated with a higher risk of cerebral haemorrhage. As expected, our data support the better safety profile of DOACs than warfarin in terms of skin and respiratory tract hemorrhagic risks. Finally, we showed how CA could play a complementary role in analyzing data from pharmacovigilance databases.
Sempervirine Inhibits Proliferation and Promotes Apoptosis by Regulating Wnt/β-Catenin Pathway in Human Hepatocellular Carcinoma
Authors: Yue Rongcai , Liu Haiping , Huang Yaxin , Wang Jing , Shi Dongmei , Su Yanping , Luo Yufei , Cai Ping , Jin Guilin , Yu Changxi
Published: December 2021

Gelsemium elegans (G. elegans) Benth., recognized as a toxic plant, has been used as traditional Chinese medicine for the treatment of neuropathic pain and cancer for many years. In the present study, we aim to obtain the anti-tumor effects of alkaloids of G. elegans and their active components in hepatocellular carcinoma (HCC) and the potential mechanism was also further investigated. We demonstrated that sempervirine induced HCC cells apoptosis and the apoptosis was associated with cell cycle arrest during the G1 phase, up-regulation of p53 and down-regulation of cyclin D1, cyclin B1 and CDK2. Furthermore, sempervirine inhibited HCC tumor growth and enhances the anti-tumor effect of sorafenib in vivo. In addition, inactivation of Wnt/β-catenin pathway was found to be involved in sempervirine-induced HCC proliferation. The present study demonstrated that alkaloids of G. elegans were a valuable source of active compounds with anti-tumor activity. Our findings justified that the active compound sempervirine inhibited proliferation and induced apoptosis in HCC by regulating Wnt/β-catenin pathway.
Ultrafast Laser Processing of Diamond Materials: A Review
Authors: Apostolova Tzveta , Kurylo Vasyl , Gnilitskyi Iaroslav
Published: December 2021

Diamond laser engineering is of great importance for designing devices, which find applications in radiation sensing and quantum technologies. A review of the present state of the art of experimental and theoretical studies on ultrashort laser irradiation of diamond is presented. For a wide range of laser parameters, the optimization of laser-induced electronic, optical and structural modifications of diamond requires quantitative understanding of the microscopic processes underlying the high electronic excitation in the material.
Interacting Effects of Cell Size and Temperature on Gene Expression, Growth, Development and Swimming Performance in Larval Zebrafish
Authors: van de Pol Iris Louise Eleonora , Hermaniuk Adam , Verberk Wilhelmus Cornelis Egbertus Petrus
Published: December 2021

Cell size may be important in understanding the thermal biology of ectotherms, as the regulation and consequences of cell size appear to be temperature dependent. Using a recently developed model system of triploid zebrafish (which have around 1.5-fold larger cells than their diploid counterparts) we examine the effects of cell size on gene expression, growth, development and swimming performance in zebrafish larvae at different temperatures. Both temperature and ploidy affected the expression of genes related to metabolic processes (citrate synthase and lactate dehydrogenase), growth and swimming performance. Temperature also increased development rate, but there was no effect of ploidy level. We did find interactive effects between ploidy and temperature for gene expression, body size and swimming performance, confirming that the consequences of cell size are temperature dependent. Triploids with larger cells performed best at cool conditions, while diploids performed better at warmer conditions. These results suggest different selection pressures on ectotherms and their cell size in cold and warm habitats.
The Heterogeneity of Inflammatory Response and Emphysema in Chronic Obstructive Pulmonary Disease
Authors: Xu Xia , Huang Ke , Dong Fen , Qumu Shiwei , Zhao Qichao , Niu Hongtao , Ren Xiaoxia , Gu Xiaoying , Yu Tao , Pan Lin , Yang Ting , Wang Chen
Published: December 2021

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by chronic inflammation, emphysema, airway remodeling, and altered lung function. Despite the canonical classification of COPD as a neutrophilic disease, blood and airway eosinophilia are found in COPD patients. Identifying the tools to assess eosinophilic airway inflammation in COPD models during stable disease and exacerbations will enable the development of novel anti-eosinophilic treatments. We developed different animal models to mimic the pathological features of COPD. Our results show that eosinophils accumulated in the lungs of pancreatic porcine elastase-treated mice, with emphysema arising from the alveolar septa. A lipopolysaccharide challenge significantly increased IL-17 levels and induced a swift change from a type-2 response to an IL-17-driven inflammatory response. However, lipopolysaccharides can exacerbate cigarette smoking-induced airway inflammation dominated by neutrophil infiltration and airway remodeling in COPD models. Our results suggest that eosinophils may be associated with emphysema arising from the alveolar septa, which may be different from the small airway disease-associated emphysema that is dominated by neutrophilic inflammation in cigarette smoke-induced models. The characterization of heterogeneity seen in the COPD-associated inflammatory signature could pave the way for personalized medicine to identify new and effective therapeutic approaches for COPD.
Regulation of Mating-Induced Increase in Female Germline Stem Cells in the Fruit Fly Drosophila melanogaster
Authors: Hoshino Ryo , Niwa Ryusuke
Published: December 2021

In many insect species, mating stimuli can lead to changes in various behavioral and physiological responses, including feeding, mating refusal, egg-laying behavior, energy demand, and organ remodeling, which are collectively known as the post-mating response. Recently, an increase in germline stem cells (GSCs) has been identified as a new post-mating response in both males and females of the fruit fly, Drosophila melanogaster. We have extensively studied mating-induced increase in female GSCs of D. melanogaster at the molecular, cellular, and systemic levels. After mating, the male seminal fluid peptide [e.g. sex peptide (SP)] is transferred to the female uterus. This is followed by binding to the sex peptide receptor (SPR), which evokes post-mating responses, including increase in number of female GSCs. Downstream of SP-SPR signaling, the following three hormones and neurotransmitters have been found to act on female GSC niche cells to regulate mating-induced increase in female GSCs: (1) neuropeptide F, a peptide hormone produced in enteroendocrine cells; (2) octopamine, a monoaminergic neurotransmitter synthesized in ovary-projecting neurons; and (3) ecdysone, a steroid hormone produced in ovarian follicular cells. These humoral factors are secreted from each organ and are received by ovarian somatic cells and regulate the strength of niche signaling in female GSCs. This review provides an overview of the latest findings on the inter-organ relationship to regulate mating-induced female GSC increase in D. melanogaster as a model. We also discuss the remaining issues that should be addressed in the future.
Leaf Trait Networks Based on Global Data: Representing Variation and Adaptation in Plants
Authors: Li Ying , Liu Congcong , Xu Li , Li Mingxu , Zhang Jiahui , He Nianpeng
Published: December 2021

The interdependence of multiple traits allows plants to perform multiple functions. Acquiring an accurate representation of the interdependence of plant traits could advance our understanding of the adaptative strategies of plants. However, few studies focus on complex relationships among multiple traits. Here, we proposed use of leaf trait networks (LTNs) to capture the complex relationships among traits, allowing us to visualize all relationships and quantify how they differ through network parameters. We established LTNs using six leaf economic traits. It showed that significant differences in LTNs of different life forms and growth forms. The trait relationships of broad-leaved trees were tighter than conifers; thus, broad-leaved trees could be more efficient than conifers. The trait relationships of shrubs were tighter than trees because shrubs require multiple traits to co-operate efficiently to perform multiple functions for thriving in limited resources. Furthermore, leaf nitrogen concentration and life span had the highest centrality in LTNs; consequently, the environmental selection of these two traits might impact the whole phenotype. In conclusion, LTNs are useful tools for identifying key traits and quantifying the interdependence of multiple traits.
Morpho-Anatomical Traits and Soluble Sugar Concentration Largely Explain the Responses of Three Deciduous Tree Species to Progressive Water Stress
Authors: Hernandez Jonathan O. , An Ji Young , Combalicer Marilyn S. , Chun Jong-Pil , Oh Sang-Keun , Park Byung Bae
Published: December 2021

A better understanding of plant drought responses is essential to improve plant water use efficiency, productivity, and resilience to ever-changing climatic conditions. Here, we investigated the growth, morpho-anatomical, physiological, and biochemical responses of Quercus acutissima Carruth., Quercus serrata Murray, and Betula schmidtii Regel to progressive water-stress. Seedlings were subjected to well-watered (WW) and water-stressed (WS) conditions while regularly monitoring the soil volumetric water content, stem diameter (SD), height, biomass, stomatal conductance (gs), intercellular CO2 concentration (Ci), and leaf relative water content (RWC). We also investigated the variation in stomatal pore (SP) area, specific leaf area (SLA), root xylem vessel diameter (VD), and total soluble sugar (TSS) concentration between treatments. After 2 months, WS significantly suppressed SD growth of Q. acutissima and B. schmidtii but had no impact on Q. serrata. Total biomass significantly declined at WS-treated seedlings in all species. WS resulted in a smaller SLA than WW in all species. The SP of WS-treated seedlings of Q. acutissima and B. schmidtii significantly decreased, whereas it increased significantly with time in Q. serrata. Larger vessels (i.e., >100 to ≤ 130) were more frequent at WS for Q. acutissima and B. schmidtii, whereas smaller vessels (i.e., >40 to ≤ 90) were more frequent at WS than at WW for Q. serrata after 8 weeks. Tylosis was more frequent at WS than WW for Q. serrata and B. schmidtii at eighth week. WS seedlings showed lower gs, Ci, and RWC compared with WW-treated ones in Q. acutissima and B. schmidtii. TSS concentration was also higher at WS-treated seedlings in two Quercus species. Overall, principal component analysis (PCA) showed that SLA and SP are associated with WS seedlings of Q. serrata and B. schmidtii and the tylosis frequency, TSS, and VD are associated with WS seedlings of Q. acutissima. Therefore, water-stressed plants from all species responded positively to water stress with increasing experimental duration and stress intensity, and that is largely explained by morpho-anatomical traits and soluble sugar concentration. The present study should enhance our understanding of drought-induced tree growth and short-term tree-seedling responses to drought.
Identification and Validation of Stable Quantitative Trait Loci for SDS-Sedimentation Volume in Common Wheat (Triticum aestivum L.)
Authors: Tian Shuai , Zhang Minghu , Li Jinghui , Wen Shaozhe , Bi Chan , Zhao Huanhuan , Wei Chaoxiong , Chen Zelin , Yu Jiazheng , Shi Xintian , Liang Rongqi , Xie Chaojie , Li Baoyun , Sun Qixin , Zhang Yufeng , You Mingshan
Published: December 2021

Sodium dodecyl sulfate-sedimentation volume is an important index to evaluate the gluten strength of common wheat and is closely related to baking quality. In this study, a total of 15 quantitative trait locus (QTL) for sodium dodecyl sulfate (SDS)-sedimentation volume (SSV) were identified by using a high-density genetic map including 2,474 single-nucleotide polymorphism (SNP) markers, which was constructed with a doubled haploid (DH) population derived from the cross between Non-gda3753 (ND3753) and Liangxing99 (LX99). Importantly, four environmentally stable QTLs were detected on chromosomes 1A, 2D, and 5D, respectively. Among them, the one with the largest effect was identified on chromosome 1A (designated as QSsv.cau-1A.1) explaining up to 39.67% of the phenotypic variance. Subsequently, QSsv.cau-1A.1 was dissected into two QTLs named as QSsv.cau-1A.1.1 and QSsv.cau-1A.1.2 by saturating the genetic linkage map of the chromosome 1A. Interestedly, favorable alleles of these two loci were from different parents. Due to the favorable allele of QSsv.cau-1A.1.1 was from the high-value parents ND3753 and revealed higher genetic effect, which explained 25.07% of the phenotypic variation, mapping of this locus was conducted by using BC3F1 and BC3F2 populations. By comparing the CS reference sequence, the physical interval of QSsv.cau-1A.1.1 was delimited into 14.9 Mb, with 89 putative high-confidence annotated genes. SSVs of different recombinants between QSsv.cau-1A.1.1 and QSsv.cau-1A.1 detected from DH and BC3F2 populations showed that these two loci had an obvious additive effect, of which the combination of two favorable loci had the high SSV, whereas recombinants with unfavorable loci had the lowest. These results provide further insight into the genetic basis of SSV and QSsv.cau-1A.1.1 will be an ideal target for positional cloning and wheat breeding programs.
Characterization of a Haematococcus pluvialis Diacylglycerol Acyltransferase 1 and Its Potential in Unsaturated Fatty Acid-Rich Triacylglycerol Production
Authors: Cui Hongli , Xu Wenxin , Zhu Xiaoli , Zhao Chunchao , Cui Yulin , Ji Chunli , Zhang Chunhui , Xue Jinai , Qin Song , Jia Xiaoyun , Li Runzhi
Published: December 2021

The unicellular green alga Haematococcus pluvialis has been recognized as an industry strain to produce simultaneously esterified astaxanthin (EAST) and triacylglycerol (TAG) under stress induction. It is necessary to identify the key enzymes involving in synergistic accumulation of EAST and TAG in H. pluvialis. In this study, a novel diacylglycerol acyltransferase 1 was systematically characterized by in vivo and in silico assays. The upregulated expression of HpDGAT1 gene was positively associated with the significant increase of TAG and EAST contents under stress conditions. Functional complementation by overexpressing HpDGAT1 in a TAG-deficient yeast strain H1246 revealed that HpDGAT1 could restore TAG biosynthesis and exhibited a high substrate preference for monounsaturated fatty acyl-CoAs (MUFAs) and polyunsaturated fatty acyl-CoAs (PUFAs). Notably, heterogeneous expression of HpDGAT1 in Chlamydomonas reinhardtii and Arabidopsis thaliana resulted in a significant enhancement of total oils and concurrently a high accumulation of MUFAs- and PUFAs-rich TAGs. Furthermore, molecular docking analysis indicated that HpDGAT1 contained AST-binding sites. These findings evidence a possible dual-function role for HpDGAT1 involving in TAG and EAST synthesis, demonstrating that it is a potential target gene to enrich AST accumulation in this alga and to design oil production in both commercial algae and oil crops.
Defining Online Hating and Online Haters
Authors: Malecki W. P. , Kowal Marta , Dobrowolska Małgorzata , Sorokowski Piotr
Published: December 2021

According to a view widely held in the media and in public discourse more generally, online hating is a social problem on a global scale. However, thus far there has been little scientific literature on the subject, and, to our best knowledge, there is even no established scholarly definition of online hating and online haters in the first place. The purpose of this manuscript is to provide a new perspective on online hating by, first, distinguishing online hating from the phenomena it is often confused with, such as trolling, cyberstalking, and online hate speech, and, second, by proposing an operational definition of online hating and online haters based on ethnographic interviews and surveys of the existing scholarly literature.
Global Trends in the Incidence, Prevalence, and Years Lived With Disability of Parkinson's Disease in 204 Countries/Territories From 1990 to 2019
Authors: Ou Zejin , Pan Jing , Tang Shihao , Duan Danping , Yu Danfeng , Nong Huiqi , Wang Zhi
Published: December 2021

Background: Parkinson's disease (PD) is an increasing challenge to public health. Tracking the temporal trends of PD burden would inform health strategies.

Methods: Data of PD burden was obtained from the Global Burden of Disease 2019. Trends in the incidence, prevalence, and years lived with disability (YLDs) of PD were estimated using the annual percentage change (EAPC) and age-standardized rate (ASR) from 1990 to 2019. The EAPCs were calculated with ASR through a linear regression model.

Results: The overall ASR of the incidence, prevalence, and YLDs of PD increased from 1990 to 2019, and their EAPCs were 0.61 (95% confidence interval [CI]: 0.58–0.65), 0.52 (95% CI: 0.43–0.61), and 0.53 (95% CI: 0.44–0.62). The largest number of PD patients was seen in the groups aged more than 65 years, and the percentage rapidly increased in the population aged more than 80 years. Upward trends in the ASR of PD were observed in most settings over the past 30 years. Incident trends of ASR increased pronouncedly in the United States of America and Norway, in which the respective EAPCs were 2.87 (95% CI: 2.35–3.38) and 2.14 (95% CI: 2.00–2.29). Additionally, the largest increasing trends for prevalence and YLDs were seen in Norway, with the respective EAPCs of 2.63 (95% CI: 2.43–2.83) and 2.61 (95% CI: 2.41–2.80). However, decreasing trends in PD appeared in about 30 countries, particularly Italy and the Republic of Moldova.

Conclusions: Increasing trends in the burden of PD were observed globally, and in most regions and countries from 1990 to 2019. Our findings suggested that the control and management of PD should be strengthened, especially when considering the aging tendency of the population.
Review on Patient-Cooperative Control Strategies for Upper-Limb Rehabilitation Exoskeletons
Authors: Dalla Gasperina Stefano , Roveda Loris , Pedrocchi Alessandra , Braghin Francesco , Gandolla Marta
Published: December 2021

Technology-supported rehabilitation therapy for neurological patients has gained increasing interest since the last decades. The literature agrees that the goal of robots should be to induce motor plasticity in subjects undergoing rehabilitation treatment by providing the patients with repetitive, intensive, and task-oriented treatment. As a key element, robot controllers should adapt to patients’ status and recovery stage. Thus, the design of effective training modalities and their hardware implementation play a crucial role in robot-assisted rehabilitation and strongly influence the treatment outcome. The objective of this paper is to provide a multi-disciplinary vision of patient-cooperative control strategies for upper-limb rehabilitation exoskeletons to help researchers bridge the gap between human motor control aspects, desired rehabilitation training modalities, and their hardware implementations. To this aim, we propose a three-level classification based on 1) “high-level” training modalities, 2) “low-level” control strategies, and 3) “hardware-level” implementation. Then, we provide examples of literature upper-limb exoskeletons to show how the three levels of implementation have been combined to obtain a given high-level behavior, which is specifically designed to promote motor relearning during the rehabilitation treatment. Finally, we emphasize the need for the development of compliant control strategies, based on the collaboration between the exoskeleton and the wearer, we report the key findings to promote the desired physical human-robot interaction for neurorehabilitation, and we provide insights and suggestions for future works.