bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanozyme-Natural Enzymes Cascade Catalyze Cholesterol Consumption and Reverse Cancer Multidrug Resistance
Authors: Du Bin , Zheng Mei , Huang Jingshu , Jiao Qingqing , Bai Yimeng , Zhao Mengmeng , Zhou Jie
Published: November 2021

Multidrug resistance is still a major obstacle to cancer treatment. The most studies are to inhibit the activity of the drug transporter P-glycoprotein (P-gp), but the effect is not ideal. Herein, a nanosystem was built based on cascade catalytic consumption of cholesterol. Cholesterol oxidase (natural enzyme, COD) was immobilized on the carrier (NH2-MIL-88B, MOF) through amide reaction, COD catalyzed the consumption of cholesterol, the reaction product H2O2 was further produced by the MOF with its peroxidase-like activity to produce hydroxyl radicals (•OH) with killing effect. Due to the high expression of CD44 receptor on the surface of tumor cells, we encapsulated chondroitin sulfate gel shell (CS-shell) with CD44 targeting and apoptosis promoting effect on the surface of DOX@MOF-COD nanoparticles, which can accurately and efficiently deliver the drugs to the tumor site and improve the effect of reversing drug resistance. Taking drug-resistant cell membrane as "breakthrough", this paper will provide a new idea for reversing multidrug resistance of tumor.
Experiencing Eight Psychotherapy Approaches Devoted to Eating Disorders in a Single Day Workshop Increases Insight and Motivation to Engage in Care
Authors: Scanferla Elisabetta , Pachoud Bernard , Gorwood Philip
Published: November 2021

PurposeFor patients with eating disorders (EDs), early engagement in care is usually considered as a positive prognostic factor. The aim of the present study is to investigate how a single-day intervention devoted to an early experiential exposure to a variety of psychotherapy approaches, supports transition to specialised care and commitment to change in patients with EDs.MethodsOne hundred and sixty-nine outpatients newly diagnosed with an ED took part in a single-day workshop for groups of up to 10 patients, where they discovered and experienced eight psychotherapeutic approaches. Motivation to change care, and level of insight were assessed at baseline and 10 days after the intervention.ResultsMotivation and commitment to take active steps toward change (expressed by the “Committed Action” composite score) significantly improved after intervention (p<0.001), and a significant number of patients specifically moved from “contemplation” to “action” stage (p<0.001). The improvement of motivation to change is significantly associated to an increase of insight capacity (p<0.001), and this for almost all dimensions.ConclusionA single-day session devoted to experiencing a range of group psychotherapies increased patients’ insight and motivation to actively engage in care. Further studies including different factors and long-term outcomes evaluation may be necessary to better establish which aspects are specifically involved in patients' increased motivation for care and confirm potential longer-term benefits of this intervention.Level of evidenceLevel V: Opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.
Chronic Pain Alters Somatosensory Evoked Potentials and Paired-pulse Inhibition in Athlete
Authors: Yamashiro Koya , Siiya Kanako , Ikarashi Koyuki , Baba Yasuhiro , Fujimoto Tomomi , Ochi Genta , Otsuru Naofumi , Onishi Hideaki , Sato Daisuke
Published: November 2021

Injuries are inevitable for athletes, and when injuries end up causing chronic pain, they usually force athletes to withdraw from training. Chronic pain is known to be caused by plastic changes in the brain; thus, the purpose of this study was to assess the somatosensory evoked potential (SEP) and the paired-pulse inhibition (PPI) in athletes suffering from chronic pain as compared to pain-free athletes. Twenty track and field (T&F) athletes, that were also undergraduate students, were recruited for this study. These athletes (12 men; 8 women) were divided into two groups of 10 based on their self-reporting of actively experiencing chronic pain (defined as pain that persisted for more than 3 months) or not. Both SEP and PPI in the primary somatosensory cortex (SI) were elicited by constant current square-wave pulses (of 0.2 ms duration) that were delivered to the right median nerve by an electrical stimulator through a surface bar electrode with a cathode proximal. Paired-pulse stimulation was set at interstimulus intervals of 30 and 100 ms. Subjects were randomly presented with 1,500 single- and paired-pulse stimuli at 2 Hz. Our measurements demonstrated a trend toward a lower N20 and P25 amplitude as well as a disinhibition of the PPI_30 ms in the athletes suffering from chronic pain. These findings suggest that chronic pain may modulate excitatory and inhibitory function of the SI in athletes as well as in patients suffering from complex regional pain syndrome or fibromyalgia.
Chronic Alcohol Reduces Bone Formation Through Inhibiting Proliferation and Promoting Aging of Endothelial Cells in Type-H Vessels
Authors: Chen Ao , Li Xiaoting , Zhao Jingyu , Zhou Jiawen , Xie Chunfeng , Chen Haiyun , Wang Qiuyi , Wang Rong , Miao Dengshun , Li Jie , Jin Jianliang
Published: November 2021

Background: Chronic alcohol is one of the leading risk factors for male osteoporosis . Angiogenesis and osteogenesis coupled by type-H vessels coordinate the biological process of bone homeostasis to prevent osteopenia. It is unknown whether alcohol inhibits type-H-vessel-dependent bone formation. Aims: This study aimed to determine whether alcohol hampers proliferation and promotes aging of endothelial cells of type-H vessels, and whether alcohol inhibits the differentiation of bone marrow-mesenchymal stem cells (BM-MSCs) into osteoblasts through reducing the number and secretion of endothelial cells in type-H vessels. Materials and Methods: Two-month-old mice fed with alcohol liquid diet (28% of calories) or normal liquid diet for two months. The tibias were isolated and detected with X-ray and micro-CT. Paraffin-embedded or frozen tibial sections were prepared and used for immunohistochemical or immunofluorescence staining respectively in vivo . Human Umbilical Vein Endothelial Cells (HUVECs) were treated with different-concentrated alcohol for 12 hours. The conditioned medium of the above HUVECs cells was collected to culture human BM-MSCs, which were induced to differentiate into osteoblasts in vitro . Results: The alcoholic diet retarded the bone growth and lead to osteoporosis, impaired bone formation of osteoblasts, and decreased CD31 hi EMCN hi type-H-vessel formation through inhibiting proliferation and promoting aging of endothelial cells in mice. Alcohol treatment obviously increased the expression of p16, while significantly decreased the expression of Bmi-1, CDK6, Cyclin D, E2F1 and BMP2 compared to vehicle. Alcohol inhibited the differentiation of BM-MSCs into osteoblasts through reducing the BMP2 secretion of endothelial cells in type-H vessels. Conclusions: Alcoholic diet impaired CD31 hi EMCN hi type-H-vessel formation through inhibiting proliferation and promoting aging of endothelial cells via Bmi-1/p16 signaling, and inhibited the differentiation of BM-MSCs into osteoblasts through reducing the BMP2 secretion of endothelial cells in type-H vessels. It provides a basis for developing a new treatment strategy targeting aging endothelial cells of type-H-vessel to prevent alcoholic osteopenia.
CXCL13 Expressed on Inflamed Cerebral Blood Vessels Recruit IL-21 Producing TFH Cells to Damage Neurons Following Stroke.
Authors: Rayasam Aditya , Kijak Julie A. , Kissel Lee , Kim Taehee , Hsu Martin , Joshi Dinesh , Laaker Collin J. , Cismaru Peter , Lindstedt Anders , Kovacs Krisztian , Vemuganti Raghu , Chiu Shing Yan , Priyathilaka Thanthrige Thiunuwan , Sandor Matyas , Fabry Zsuzsanna
Published: November 2021

Background: Ischemic stroke is a leading cause of mortality worldwide, largely due to the inflammatory response to brain ischemia during post-stroke reperfusion. Despite ongoing intensive research, there have not been any clinically approved drugs targeting the inflammatory component to stroke. Preclinical studies have identified T cells as pro-inflammatory mediators of ischemic brain damage, yet mechanisms that regulate the infiltration and phenotype of these cells are lacking. Further understanding of how T cells migrate to the ischemic brain and facilitate neuronal death during brain ischemia can reveal novel targets for post-stroke intervention.Methods: To identify the population of T cells that produce IL-21 and contribute to stroke, we performed transient middle cerebral artery occlusion (tMCAO) in mice and performed flow cytometry on brain tissue. We also utilized immunohistochemistry in both mouse and human brain sections to identify cell types and inflammatory mediators related to stroke-induced IL-21 signaling. To mechanistically demonstrate our findings, we employed pharmacological inhibitor anti-CXCL13 and performed histological analyses with Cresyl violet to evaluate its effects on brain infarct damage. Finally, to evaluate cellular mechanisms of stroke, we exposed mouse primary neurons to oxygen glucose deprivation (OGD) conditions with or without IL-21 and measured cell viability, caspase activity and JAK/STAT signaling.Results: Flow cytometry on brains from mice following tMCAO identified a novel population of cells IL-21 producing CXCR5+ CD4+ ICOS-1+ T follicular helper cells (TFH) in the ischemic brain early after injury. We observed augmented expression of CXCL13 on inflamed brain vascular cells and demonstrated that inhibition of CXCL13 protects mice from tMCAO by restricting the migration and influence of IL-21 producing TFH cells in the ischemic brain. We also illustrate that neurons express IL-21R in the peri-infarct regions of both mice and human stroke tissue in vivo. Lastly, we found that IL-21 acts on mouse primary ischemic neurons to activate the JAK/STAT pathway and induce Caspase 3/7 mediated apoptosis in vitro. Conclusion: These findings identify a novel mechanism for how pro-inflammatory T cells are recruited to the ischemic brain to propagate stroke damage and provide a potential novel therapeutic target for stroke.
The Impact of Catheter Removal Time on Urinary Continence and Overactive Bladder Symptoms After Robot-Assisted Radical Prostatectomy: A Retrospective Analysis of Consecutive 250 Cases From a Single Institution
Authors: Hao Han , Chen Xu , Liu Yue , Si Longmei , Chen Yuke , Zhang Meng , Yu Wei , Song Yi , Wu Shiliang , Zhang Zhongyuan , Zhao Zheng , Shen Cheng , Han Wenke
Published: November 2021

Background After radical prostatectomy, the optimal length of postoperative catheterization time remains to be determined. This study investigates the impact of catheter removal time on urinary continence and overactive bladder symptoms after robot-assisted radical prostatectomy (RARP).Methods Two hundred and fifty consecutive patients underwent RARP by a single surgeon between November 2020 and May 2021. Time to catheter removal was categorized into 7, 10, and ≥ 14 days. Continence was defined as no more than 1 pad used or no more than 20 grams of urine leakage per 24 hours. The patients' continence rates and overactive bladder symptom score (OABSS) were assessed at 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks after catheter removal.Results Overall, continence rates were 36% 48 hours after catheter removal, 55.6% 1 week, 74.8% 4 weeks, 98.4% 12 weeks, and 100% 24 weeks after catheter removal. The median time to regain continence was 1 week. After stratification according to catheterization time, no significant difference in continence rates was found between different groups at each time point after catheter removal. Longer catheterization was not an independent predictor of continence recovery (10 days: OR 0.985, 95% CI 0.689-1.409, p = 0.936; ≥14 days: OR 1.194, 95% CI 0.869-1.642, p = 0.274). The presence of diabetes was associated with worse continence outcomes (OR 1.535, 95% CI 1.105-2.132, p = 0.011). The mean OABSS of patients in the continent group were significantly lower than the incontinent group at 48 hours, 1 week, and 4 weeks after catheter removal. No significant difference in OABSS was found between different catheterization time groups at each time point after catheter removal.Conclusions Our results demonstrated that different catheterization time (7 days, 10 days, ≥14 days) is not associated with short-, intermediate-, long-term continence outcomes or overactive bladder symptoms.
PALT (Partial Allogeneic Limbal Transplantation): A New Surgical Technique For Limbal Stem Cell Deficiency
Authors: Kesper Christiane , Viestenz Anja , Hammer Thomas , Heinzelmann Joana , Foja Sabine , Viestenz Arne
Published: November 2021

PurposeLimbal stem cell deficiency (LSCD) is a rare but extremely relevant disease of the eye. LSCD patients often require a variety of surgical procedures, including keratoplasty in some cases. However, the outcome of these surgeries, including opacification and revascularization, is often frustrating due to LSCD relapse.MethodsWe developed a new surgical technique for the treatment of LSCD in which partial allogenic limbal transplantation (PALT) is carried out as part of penetrating keratoplasty (PK). After the PK, 1-8 slices from the limbal tissue of the donor graft are prepared and placed under the double running sutures attaching the corneal graft. This procedure was performed on 14 patients with LSCD, caused by severe ocular burn in 5 cases and by infection in 9. Between one and eight limbal transplants were used depending on the extension of the LSCD. ResultsAll 14 patients showed stable or increased visual acuity after the PALT surgery compared to their preoperative visual acuity. All of the grafts were integrated into the superficial corneal layers without progression of corneal vascularization beyond the limbal grafts. The median follow-up period was 12 months on average.ConclusionThe PALT method seems to be a promising surgical procedure for the treatment of patients with LSCD. It can be properly carried out in the context of keratoplasty and does not require a separate donor tissue. The PALT grafts may offer the possibility of constructing a new limbal region, resulting in stable or even increased visual acuity and the absence of corneal vascularization.
Comparative Study on Pseudaulacaspis Pentagona Resistance of Four Different Cultivars of Kiwifruit
Authors: Zheng Xianzhe , Li Qiaohong , Zhang Qian , Wu Guanle , Tao Ke , Deng Wei , Zhuang Qiguo
Published: November 2021

Background:Kiwifruit is a common and popular fruit around the world. However, white peach scale (Pseudaulacaspis pentagona) [Targioni-Tozzetti], a scale insect with a wide range of hosts, seriously affects the yield and quality of kiwifruit. To investigate the differences in resistance of different kiwifruit cultivars to Pseudaulacaspis pentagona, cellular structure and gene expression assays were used to explain the mechanism. Results:In this study, based on the stability of the rate of injury fruit, we selected four cultivars from fifty kiwifruits for in-depth study, including “LC-04285”, “CF-3”, “DA-7B” and “Hayward”. By analyzing the differences in the anatomical structure of the canes of these cultivars, we found that the resistant cultivar "LC-04285" had thicker cuticle, denser epidermis and cortex. The real-time quantitative PCR data indicated that the expression levels of genes related to cuticle synthesis and formation of epidermis and cortex are also higher in “LC-04285”. Jasmonic acid (JA) is an important hormone involved in plant defense against many insect pests. In this study, we found that the expression levels of JA receptor COI1 were higher in “LC-04285”. However, the expression levels of AcJAZs, which played negative role in JA signaling, were higher in susceptible cultivar “Hayward”. Besides, the expression levels of AcICS, AcPAL4, AcPAL5, and AcNPRs, which were involved in salicylic acid (SA) synthesis and SA response, were also higher in “LC-04285”. Conclusions:Our results revealed the mechanism of kiwifruit resistance to P. pentagona at the molecular and cellular levels. This study provided useful guidance for breeding insect-resistant kiwifruit in future.
Microvirga Terrestris sp. nov., and Microvirga Arvi sp. nov., Two Novel Species Isolated From Soil in South Korea
Authors: Damdintogtokh Tuvshinzaya , Park Yuna , Maeng Soohyun , Oh Hye Jin , Bang Minji , Bai Jaewoo , Kim Myung Kyum
Published: November 2021

Two novel Gram-stain-negative, aerobic, rod shaped bacterial strains BT290T and BT689T were isolated from soil collected in South Korea. Colony morphologies of both strains were circular and convex while the colors of BT290T and BT689T were light-pink and white, respectively. Phylogenetic analysis based on 16S rRNA gene sequences revealed that BT290T and BT689T belong to a distinct lineage within the genus Microvirga (family Methylobacteriaceae, order Rhizobiales, class Alphaproteobacteria, phylum Proteobacteria, kingdom Bacteria). The 16S rRNA gene sequence similarity between two strains was 97.9 %. Both strains had the similar quinone system, with ubiquinone 10 (Q-10) as the major respiratory quinone. The major polar lipids of strains BT290T and BT689T were phosphatidylethanolamine (PE), diphosphatydilglycerol (DPG), phosphatidylcholine (PC) and phosphatydilglycerol (PG). The major cellular fatty acids of strain BT290T were C18:1 ω7c (58.2 %) and C16:0 (17.7 %), while those of strain BT689T were C18:1 ω7c (61.8 %) and C16:0 (10.8 %).On the bases of polyphasic analysis (phylogenetic, chemotaxonomic and biochemical), strains BT290T and BT689T can be suggested as novel bacterial species within the genus Microvirga and the proposed names are Microvirga terrestris and Microvirga arvi, respectively. The type strain of Microvirga terrestris is BT290T (= KCTC 72367T=NBRC 114844T) and the type strain of Microvirga arvi is BT689T (= KACC 22016T = NBRC 114858T), respectively.
α2-Macroglobulin-Rich Serum As a Master Inhibitor of Inflammatory Factors Attenuates Cartilage Degeneration in a Mini Pig Model of Osteoarthritis Induced By “Idealized” Anterior Cruciate Ligament Reconstruction
Authors: Zhao Ruipeng , Wei Xiaochun , Zhang Chengming , Wu Hongru , Xiang Chuan , Li Haoqian , Duan Wangping , Duan Zhiqing , Li Chuanjiang , Zhao Yu , Huang Lingan
Published: November 2021

Background: α2-Macroglobulin (α2M) is important for chondral protection in post-traumatic osteoarthritis (PTOA). However, its injection into xenogeneic joint cavities has safety hazards, limiting clinical applications. Exploring serum α2M-enriching strategies and the therapeutic effect and mechanism of α2M-rich serum (α2MRS) autologous joint injection to treat PTOA has significant value.Methods: A unique filtration process was used to concentrate α2M from serum. Human osteoarthritic chondrocytes induced with interleukin (IL)-1β were used to evaluate catabolic enzymes, cell proliferation, apoptosis, and gene expression 24h after α2MRS treatment. Eighteen mature female mini pigs were randomized to three groups, sham (n = 6), “idealized” anterior cruciate ligament autograft reconstruction (IACL-R) (n = 6), and IACL-R+α2MRS (n = 6). Expression of inflammatory factors in the synovial fluid (SF) was measured using Luminex assays. Gait features were recorded using the Tekscan Walkway system. The extent of PTOA progression was evaluated using imaging, real-time PCR , and histology 3 months post-surgery.Results: The α2M concentration in α2MRS was higher than that in human and mini pig serum, respectively. In vitro, α2MRS significantly promoted human chondrocyte proliferation (p < 0.001) and reduced apoptosis (p < 0.001) and chondrocyte catabolic cytokine gene transcription (p < 0.001) and secretion (p < 0.001). In vivo, SF concentrations of all tested inflammatory factors were significantly lower in the IACL-R+α2MRS group than in the IACL-R group (p < 0.001). All gait parameters in the IACL-R+α2MRS group returned to normal significantly early compared to those in the IACL-R group (p < 0.05). Imaging , histology, and biochemistry data showed that cartilage degeneration in the IACL-R+α2MRS group was significantly diminished relative to that in the IACL-R group (p < 0.001).Conclusion: Injecting α2MRS into the joint cavity after IACL-R can significantly delay articular cartilage degeneration.
Glycerol Monolaurate Attenuated Immunological Stress and Intestinal Mucosal Injury by Regulating the Gut Microbiota and AMPK/NF-κB/Nrf2 Signaling Pathway in Lipopolysaccharide-Challenged Broilers
Authors: Kong Linglian , Wang Zhenhua , Xiao Chuanpi , Zhu Qidong , Song Zhigang
Published: November 2021

Background

Antibiotic residues and resistance issues have led to the ban on antibiotic growth promoters in the poultry industry. Targeted dietary supplementation such as glycerol monolaurate (GML) has been found to ameliorate the negative effects of restriction on the use of antibiotic growth promoters by modulating the animal immune system and intestinal health. However, the mechanism by which GML contributes to the health and growth of broilers is indistinct. This study was conducted to investigate the effects of GML on immunity, intestinal barrier function, and cecal microbiota profiles in lipopolysaccharide (LPS)-challenged broilers.
Results

The results revealed that dietary GML intake augmented serum immunoglobulin A and G levels in LPS-challenged broilers. GML supplementation normalized LPS-induced variations in serum interleukin-6, interferon-γ, and LPS levels; jejunal villus height; and gene expression of interleukin-6, macrophage inflammatory protein-3α, toll-like receptor 4, nuclear factor kappa-B (NF-κB), caspase-1, tight junction proteins, adenosine monophosphate-activated protein kinase α1, nuclear factor-erythroid 2-related factor 2, and superoxide dismutase-1. GML administration ameliorated LPS-induced peroxidation by reducing malondialdehyde content and increasing antioxidant enzyme activity. Dietary GML intake enhanced the abundances of cecal probiotics such as Blautia, Lactobacillus, and Coprobacter in challenged broilers. The LPS-induced reduction in Anaerostipes, Pseudoflavonifractor, and Gordonibacter abundances in the cecum was inhibited by GML supplementation. Dietary GML intake was positively correlated with alterations in antioxidant enzyme activities and adenosine monophosphate-activated protein kinase (AMPK) α1, nuclear factor-erythroid 2-related factor 2 (Nrf2), and zonula occludens-1 levels. The genera Anaerostipes, Lachnospira, Gordonibacter, Lachnospira, Marvinbryantia, Peptococcus, and Pseudoflavonifractor were linked to attenuated inflammation and improved immunity and antioxidant capacity of LPS-challenged broilers.
Conclusion

Dietary GML intake alleviated LPS-induced immunological stress and intestinal injury in broilers. This beneficial effect of GML supplementation was attributed to the suppression of inflammation and oxidative stress by regulation of cecal microbiota and the AMPK/NF-κB/Nrf2 signaling pathway in LPS-challenged broilers.
Combined disruption of the thoracic spine and costal arch fracture: An indicator of a severe chest trauma
Authors: Schulz-Drost Stefan , Kloesel Stephan , Kühling Jan Carsten , Ekkernkamp Axel , Bakir M. Sinan
Published: November 2021

Background
Blunt high-energy trauma increase the risk of associated thoracic and accompanying abdominal organ injuries in chest trauma. A higher overall injury severity has been shown for sternovertebral injuries caused by a flexion-compression mechanism. Literature for a hyperextension-distraction mechanism equivalent to a costal arch fracture combined with a thoracic spinal fracture is sparse. Therefore, we want to show the clinical significance of this entity.
Methods
A retrospective analysis of our level-one trauma center collective of severely injured patients was performed. Patients from 2013 to 2019 that involved an Injury Severity Score (ISS) ≥16 were screened for the combined thoracovertebral injury entity and analyzed concerning its accident mechanism, the injury spectrum, and the clinical course.
Results
The thoracovertebral injury entity is rare. Three male patients (50–65 years old) with ISS of 57, 41, and 20 could be observed from over 1000 severely injured. All patients suffered from high-energy trauma and from tearing of the thoracic vertebrae regions 7–9. The costal arch was torn in the anterior area. All cases showed a posterolateral serial rib fracture, a traumatic intercostal pulmonary hernia, and an avulsion of the diaphragm. Two patients sustained further life-threatening injuries, such as severely bleeding avulsion to the azygos vein and a rupture of the spleen. The physicians performed exploratory thoracotomy, closure of the pulmonary hernia, re-fixation of the diaphragm and angle-stable plate osteosynthesis of the fractured ribs, including the costal arch. The spine was fixed dorsally using a screw-rod system. The patients were discharged home with independent mobility and without neurological damage.
Conclusions
This thoracovertebral injury entity is associated with high overall injury severity and life-threatening thoracoabdominal injuries. Injuries to the costal arch can act as an indicator of severe trauma. They should be detected thorough clinical examination and assessment of the trauma CT in the soft tissue window.
Factors associated with normal physical function in patients with rheumatoid arthritis of different ages
Authors: Komiya Yoji , Sugihara Takahiko , Hirano Fumio , Matsumoto Takumi , Kamiya Mari , Sasaki Hirokazu , Hosoya Tadashi , Kimura Naoki , Ishizaki Tatsuro , Mori Masaaki , Tohma Shigeto , Yasuda Shinsuke , Matsui Toshihiro
Published: November 2021

Background

To investigate factors associated with normal physical function of middle-aged (55-64), old (65-74) or very old (75-84) patients with rheumatoid arthritis (RA).
Methods

Data from RA patients in the National Database of Rheumatic Diseases in Japan (NinJa) were extracted from April 2017 to March 2018. Factors associated with impaired physical function (Health Assessment Questionnaire Disability Index [HAQ-DI] >0.5) were analyzed by multivariable logistic regression. Association of glucocorticoids (GCs) and age with impaired physical function were presented as adjusted odds ratio (OR) for the 5 groups relative to middle-aged patients without GCs as the reference group.
Results

Low disease activity (3.3< simplified disease activity index [SDAI] ≤11) or remission (SDAI ≤3.3) was achieved in 3,466 (31.4%) or 3,021(27.4%) of 11,036 patients aged 55-84, respectively. To reduce the influence of joint destruction on HAQ-DI, we assessed the 3,708 patients in both SDAI ≤11 and Steinbrocker stage I/II. About half of the very old patients were receiving methotrexate, which was the lowest proportion amongst the three age groups. GCs were continued in 32.6% of very old patients, and the proportion was higher than in old and middle-aged patients. On the other hand, 16.2% of the very old patients received biological disease-modifying anti-rheumatic drugs (bDMARDs), and the proportions were similar among the three groups. SDAI was higher in patients with HAQ-DI >0.5 at all ages, and GCs was used more frequently in the old and very old patients with HAQ-DI >0.5, compared to those with HAQ-DI ≤0.5. To minimize the influence of disease activity on HAQ-DI, we selected the 2078 patients in both remission and stage I/II. Multivariable analysis revealed the use of GCs further increased the adjusted OR from 4.01 (95% confidence interval [CI] 2.30-6.99) to 6.81 (95%CI 3.65-12.7) in the very old patients, while the adjusted OR was 2.03 (95%CI 1.17-1.13) in the old patients without GCs, 2.22 (95%CI 1.13-4.36) in the old patients with GCs, and 0.73 (95%CI 0.21-2.56) in the middle-aged patients with GCs.
Conclusions

The negative impact of GCs was likely to most strongly influence physical function of very old patients than middle-aged or old patients.
The Influence of Concrete and Urban Water Quality On The Growth of An Invasive Weed (Salix Spp.) in One of Australia’s Most Endangered Aquatic Environments.
Authors: Purdy Katherine , Reynolds Jason K , Wright Ian Alexander
Published: November 2021

Riparian vegetation along urban streams and wetlands is frequently dominated by invasive weeds. Elevated nitrogen and phosphorous in urban waters and soils are well-known to encourage invasive urban weeds, but this research demonstrates that other urban geochemical contaminants may also be influential. Previous studies have demonstrated that the dissolution of urban concrete is a poorly recognised source of modified water and soil geochemistry, which may enhance the growth of some invasive weeds. This study investigated the relationship between urban water quality and the growth of an invasive urban riparian weed, willow (Salix spp.) to examine the contribution of concrete materials. The study used water from a wetland in the Greater Blue Mountains World Heritage Area. These wetlands have a unique biodiversity but are fragile and susceptible to degradation from human activity. Many are in urban catchments and are frequently dominated by invasive weeds, including Salix spp. In this study, willow cuttings were grown in a laboratory using four water treatments: pristine, urban, and pristine water exposed to two different concrete materials. The urban and concrete water treatments had higher pH, salinity, calcium, potassium, and higher concentration of several metals and were associated with increased growth of Salix spp. We suggest that the modification of urban water and riparian soil chemistry by urban concrete materials may contribute to the success of invasive species in urban wetlands and riparian zones. Some metals (barium, strontium) were present in urban water and in pristine water exposed to concrete and bioaccumulated in plant tissue.
Pediatric Tuina For Functional Constipation In Children: Study Protocol For A Randomized Controlled Trail
Authors: Zhang Xinghe , Hu Luan , Li Li , Wang Yuanwang , Zhang Can , Su Jinyan , Di Hua , Gao Qing , Tai Xiantao , Guo Taipin
Published: November 2021

Background: Functional constipation (FC) is a common functional gastrointestinal disorder (FGID), which brings many negative impacts to the children’s daily life. Pediatric Tuina has been proved to be a potential therapy for functional constipation (FC). However, the evidence for its effectiveness and safety is insufficient due to the lack of high-quality study. This study aims to evaluate the efficacy and safety of pediatric Tuina for children with FC.Methods/design: This study is a randomized, controlled, multicentre, clinical trial. We will include 176 children with FC from five hospitals. The participants will be randomly allocated into two groups: the pediatric Tuina group and the Medilac-Vita group. This study will include a 1-week actual treatment period and a 2-week follow-up period. Primary outcomes are weekly spontaneous bowel movements (SBMs), weekly complete spontaneous bowel movements (CSBMs). The secondary outcomes are effective rate, stool form, distress sensation, and glycerine enema rate. The assessment will be performed each week. Adverse event will be monitored in treatment period and follow-up period.Discussion: This study is designed to evaluate the efficacy and safety of pediatric Tuina for children with FC, and we hypothesize that pediatric Tuina is more effective than probiotics. It will provide reliable evidence and support for the treatment of FC by pediatric Tuina.Trail registration: This protocol was registered in Chinese Clinical Trial Registry (ChiCTR2100046485).
Cellular and Humoral Immune Response to SARS-CoV-2 mRNA Vaccines in Patients Treated with either Ibrutinib or Rituximab
Authors: Bacova Barbora , Kohutova Zuzana , Zubata Ivana , Gaherova Lubica , Kucera Petr , Heizer Tomas , Mikesova Marcela , Novak Jan
Published: November 2021

Patients treated with B-cell targeting therapies like Rituximab or Ibrutinib have decreased serological response to various vaccines. In this study, we tested serological and cellular response to SARS-CoV-2 mRNA vaccines in 16 patients treated with Ibrutinib, 16 treated with maintenance Rituximab, 18 patients with chronic lymphocytic leukaemia (CLL) with watch and wait status and 21 healthy volunteers. In comparison to the healthy volunteers, where serological response was achieved by 100% subjects, patients on B-cell-targeting therapy (Ibrutinib and Rituximab) had their response dramatically impaired. The serological response was achieved in 0% of Rituximab treated, 18% of Ibrutinib treated and 50% of untreated CLL patients. Cell-mediated immunity analysed by the whole blood Interferon-γ Release immune Assay developed in 80% of healthy controls, 62% of Rituximab treated, 75% of Ibrutinib treated and 55% of untreated CLL patients. The probability of cell-mediated immune response development negatively correlates with disease burden mainly in CLL patients. Our study shows that even though the serological response to SARS-CoV-2 vaccine is severely impaired in patients treated with B-cell-targeting therapy, the majority of these patients develop sufficient cell-mediated immunity. The vaccination of these patients therefore might be meaningful in terms of protection against SARS-CoV-2 infection.
Efficient THz Generation by Nonlinear Interaction of Gaussian Laser Beam With the Anharmonic and Rippled CNTs Aligned Vertically in the Array
Authors: Kumar Sandeep , Vij Shivani , Kant Niti , Thakur Vishal
Published: November 2021

We purpose a theoretical analysis for the generation of efficient terahertz (THz) radiation by using the nonlinear interaction of Gaussian laser beam with vertically aligned anharmonic, and rippled carbon nanotubes (CNTs) array. This array of vertically aligned carbon nanotubes (VA-CNTs) is embedded on the base of the dielectric surface. The VA-CNTs have been magnetized by applying a static magnetic field mutually perpendicular to the direction of propagation of the Gaussian beam and length of CNTs. The Gaussian laser beam passing through the CNTs exerts a nonlinear ponderomotive force on the electrons of CNTs and provides them resonant nonlinear transverse velocity. This produces the nonlinear current which is further responsible for the generation of THz radiation. The anharmonicity plays a vital role in the efficient generation of THz radiation. The anharmonicity arises due to the nonlinear variation of restoration force on the various electrons of CNTs. This anharmonicity in the electrons of CNTs helps in broadening the resonance peak. We have observed that externally applied static magnetic field 110 kg to 330 kg) also paves the way for the enhancement of the normalized THz amplitude.
Structural Transformation Path Across Countries: Is It Systematic Pattern
Authors: Padder Altaf Hussain , Mathavan B
Published: November 2021

The structural transformation across the economic sectors is one of the prominent features that go together with economic development. The paper scrutinizes whether developing and low-income countries follow the similar path and pattern of structural transformation by which the developed countries are following or followed this threshold and are now experiencing a shift from the industrial sector to the service sector. The structural transformation paths of developed countries are almost identical, but the pattern of sectoral output shares varies from that of developing countries. The research reveals a fascinating finding i.e., low-income countries outperform middle-income countries and some major countries in terms of the pace of structural transformation from agriculture to service sector.
DOA Estimation of LFM Signal Based on Krylov Subspace Method
Authors: BAKHSHI hamidreza , Lohrasbipeyde Hannan
Published: November 2021

Direction of arrival estimation (DOA) of LFM signal is an essential task in radar, sonar, acoustics and biomedical. In this paper, a short time Fourier transform multi-step knowledge aided iterative generalized minimum residual (STFT-MS-KAI-GMRES) approach is presented to amend the angle measurement of this signal. A three stage algorithm is proposed. First, the process is initiated with formulating an estimation algorithm for the carrier frequency and chirp rate, followed by calculation of STFT of the output of array element; this yields a spatial time-frequency distribution (STFD) matrix. Next, the Krylov subspace-based estimation algorithm is formulated in the presence of MS-KAI-ESPRIT algorithm. If the number of antennas increases, the accuracy of the algorithm will increase, but we will incur more communication costs. Results are presented showing attainment of the CRLB by STFT-MS-KAI-GMRES the for an adequately large signal to noise ratio (SNR). An important feature of the method presented in the current study is the low computational complexity that has higher suitability for practical applications.
Rate of Recovery and Symptomatic Efficacy of a Polyherbal AYUSH Formulation in the Treatment of SARS CoV-2 disease: A Single-arm trial
Authors: Kanchibhotla Divya , Harsora Prateek , Subramanian Saumya , reddy Ravi , Venkatesh Hari
Published: November 2021

Background

The COVID-19 pandemic, caused by the human coronavirus SARS- CoV-2, has led to millions of deaths across the globe. Not only is the SARS-CoV-2 virus highly infectious, it also mutates very easily. This creates additional challenges for development of robust therapeutic solutions. Along with modern system of healthcare, there is a definite need for exploring natural plant based antiviral compounds directed against the SARS CoV-2 virus.
Objective

The present observational study investigates the efficacy of an Ayurvedic polyherbal formulation of 19 ingredients, NOQ19, in the management of COVID-19.
Methodology:

A single arm, single centric, open label study design was adopted for this feasibility study. 161 RT-PCR positive COVID-19 patients were enrolled. The enrolled participants were provided the Ayurvedic intervention, 2 tablets of NOQ19, thrice daily along with the standard of care treatment. Follow up COVID-19 RT- PCR tests were conducted on Day 5, Day 10 and Day 14, or until the patient turned negative. The time required for testing negative on the RT-PCR test or becoming asymptomatic was noted.
Results

A subjective analysis demonstrated that 74% of patients turned RT-PCR negative within 5 days of taking NOQ19. Additionally, 98% of the subjects turned RT-PCR Negative on Day 10 after taking NOQ19 in addition to the standard of care treatment of Vitamin C, Zinc and antipyretic (as necessary). None of the participants reported any adverse or side effects to the medication.
Conclusion

NOQ19 Ayurvedic polyherbal formulation can be an effective and safe option for the symptomatic management of COVID-19.
Nrf2 Regulates Microglia-Mediated Phagocytosis and Neuroinflammation Following Intracerebral Hemorrhage
Authors: Liu Lirong , Bao Shuangjin , Yao Zhenjia , Bai Qinqin , Liang Chuntian , Zhang John H. , Fu Pengcheng , Wang gaiqing
Published: November 2021

Background
To explore the effect of microglial functional transformation in hematoma clearance following intracerebral hemorrhage (ICH), and investigate whether Nuclear factor erythroid 2-related factor 2 (Nrf2) -mediated microglial phagocytosis and inflammatory response is beneficial for hematoma clearance and functional recovery in vitro and in vivo experiments after ICH.
Methods
In vitro experiments, BV-2 cells were cultured and randomly divided into 4 groups: normal control, microglia + Nrf2-siRNA (100 nmol/L), microglia + monascin (15 µM), microglia + Xuezhikang (200 µg/mL). In vivo experiments, 42 mice were divided into sham, ICH+vehicle, ICH+Nrf2-/-, ICH+monascin (10mg/kg/day, twice) and ICH+Xuezhikang (0.2g/kg/day, twice). Neurologic scores, hemoglobin levels, microglial phagocytosis, brain expression of CD80 /Trem1/TNF-α (pro-inflammatory cytokines) as well as CD206/Trem2/BDNF (anti-inflammatory cytokines) were analyzed at 72 hours after surgery.
Results
The results showed that Nrf2 agonists improved neurological deficits and decreased hemoglobin levels after ICH. The administration of Nrf2 agonist- monascin/ Xuezhikang enhanced microglia-mediated phagocytosis of erythrocytes and bioparticles by up-regulating Nrf2. Alternatively, monascin/Xuezhikang promoted the expressions of Triggering receptor II expressed on myeloid cells (Trem2), CD206 and BDNF, while inhibited the expressions of Trem1,CD80 and TNF-αexpressed in microglia. Conversely, Nrf2 inhibition (Nrf2 siRNA or Nrf2-/-) showed the opposite results following ICH.
Conclusions
Microglial functional transformation are involved in hematoma clearance following ICH. Nrf2 activation contributes to microglial functional transformation and phagocytic responses then exerts its neuroprotection after ICH. Nrf2 activator (Monascin/Xuezhikang) enhances hematoma clearance and alleviates neuroinflammation via the regulation of microglial functional alteration following ICH.
Preoperative Anatomy Parameters in Implantable Collamer Lenses
Authors: Xue Yanzhen , Guo Yonghong , Zhao Ruibo
Published: November 2021

Purpose: To determine patient preoperative anatomical features and the parameters of implantable collamer lenses (ICLs) relevant in explaining vault variability.Setting: Ophthalmology Xi’an Aier Gucheng Eye hospital , Xi’an China.Design: Retrospective case series.Methods:This study comprised 88 eyes of 45 patients implanted with myopic or toric ICLs between May 2021 and August 2021.Pentacam imaging was used for assessing white-to-white (WTW) diameter, central keratometry, anterior chamber depth(ACD), central corneal thickness and vault. Anterior-segment optical coherence tomography（AS-OCT） was used to measure the horizontal anterior chamber angle distance (ATA). Ultrasound biomicroscopy (UBM) was used to measure horizontal and vertical sulcus to sulcus(vSTS). According to different ACD,we divide ACD into shallow group(2.8 to 3.2 mm),medium group(3.2 to 3.5 mm),and deep group(＞3.5mm).Results: Linear regression analysis found significant correlation between WTW diameters and ATA diameters( y= 0.9605x+0.1491,R² = 0.9148),with a coefficient of determinant of 0.9148 (P＜0.01). Linear regression analysis found significant correlation between hSTS and vSTS（y=0.9855x-0.0178,R²=0.1979）,with a coefficient of determinant of 0.1979 (P＜0.01). WTW diameters showed statistically significant difference in shallow and medium ACD (t=-3.28,P＜0.01 ), significant difference in shallow and deep ACD (t=-4.69,P＜0.01 ),there was no correlation in medium and deep ACD(t=-1.41,P＞0.05 ). There was a statistically significant correlation between WTW diameters and hSTS diameters when the ACD was less than 3.5 mm (t=-0.451, P=0.000) (t=1.406, P=0.026),but weak correlation when the ACD was bigger than 3.5 mm(t=1.594, P=0.051). ATA and WTW with a mean difference close to zero(-0.66 mm). Despite the relatively high correlation (intraclass correlation co-efficient =0.689), the range of agreement is quite broad (1.33 mm).Conclusions:ATA measured with AS-OCT can not be used interchangeably with WTW obtained with Pentacam. WTW diameters and hSTS diameters have a statistically significant correlation when the ACD was less than 3.5 mm. WTW, ATA, hSTS and vSTS all should be considered during design the size of lens and regulating the vault after surgery.
The effect of halogens (F, Cl) on the near-liquidus crystallinity of a hydrous trachyte melt
Authors: Feisel Yves , Castro Jonathan M. , Helo Christoph , Dingwell Donald B.
Published: November 2021

The effect of F and Cl on the liquidus temperature of a hydrous (~3.5–4 wt% H2O) trachytic melt (~66 wt% SiO2) at 925 to 990 °C and at 100 MPa has been experimentally investigated. We employed a novel disequilibrium approach involving diffusion couple experiments with the two-diffusion couple end-members differing solely in halogen concentrations. A shift of the liquidus temperature by ~50 °C was observed between a halogen-poor and halogen-enriched melt. Each experiment spanned the entire range of F and Cl concentrations between the two end-member compositions. We determined the halogen concentrations at the transition from crystal-bearing to crystal-free melt. These concentrations correspond to the liquidus halogen concentrations of the melt at each experimental temperature. We demonstrate that there is a limiting halogen concentration (~0.19–0.52 wt% F; ~0.07–0.24 wt% Cl), below which the melt crystallizes spherulitic clinopyroxene during heating to the run temperature. At high temperatures, upon diffusion of F and Cl into the halogen-poor melt, those crystals dissolve, leaving behind a dissolution front parallel to the diffusion interface. We propose that the dissolution is a consequence of F and Cl complexing with some of the main cationic components of clinopyroxene (Mg, Fe, Ca), thereby destabilizing this phase. Thus, the experimental dissolution of clinopyroxene is a manifestation of a liquidus depression caused by increased halogen content. Our results show that the liquidus shifts at a rate of ~1575(379) K/mol% of F and Cl in the melt, which is a minimum estimate, assuming both halogens equally drive dissolution. This liquidus depression is valid for a range of halogen concentrations (~0.06–0.87 wt% F; ~0.06–0.36 wt% Cl) and the experimental temperatures. Our findings illustrate that the degassing of halogens during or prior to an eruption can enhance crystallization in the melt and therefore influence magma physical properties that may ultimately affect eruption style.
DYNAMIC RESPONSE AND STABILITY ANALYSES OF AKOSOMBO DAM USING NUMERICAL ANALYSIS
Authors:   Department of Mechanical,Aerospace and Civil Engineering, University of Manchester, Manchester, UK., A. Irinyemi Stephen , Lombardi Domenico ,   Department of Mechanical,Aerospace and Civil Engineering, University of Manchester, Manchester, UK., M. Ahmad Syed ,   Department of Mechanical,Aerospace and Civil Engineering, University of Manchester, Manchester, UK.
Published: November 2021

Dams are very important in Ghanas economic development and environmental improvement. Although Ghana dams are seismically far from the active zone, accurately analysed dams should be evaluated since failure could severely impact the people in the flood environment and the regions economy on a large scale. This paper proposes a numerical procedure for the static, slope stability, and dynamic analysis of the Akosombo embankment dam. Nineteen horizontal acceleration time histories recorded data was used based on Maximum Design Earthquake (MDE), Maximum Credible Earthquake (MCE), Design Basis Earthquake (DBE) and Operating Basis Earthquake (OBE) data. The numerical results estimated showed that the Akosombo embankment dam is likely to experience moderate deformations during the different design earthquakes. The result also indicated that non-linear analysis capable of capturing dominant non-linear mechanisms could be used to assess the stability of embankment dams. The factor of safety (FS) calculated was greater than 1.5 for high reservoir, rapid drawdown condition and low reservoir condition whereas, the FS values were found to be 1.42 for slow drawdown condition.