bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Natural inhibitor agianst L1 beta-lactamase present in Stenotrophomonas maltophilia
Authors: H Sreenithya K , Jade Dhananjay , Harrison Michael , Sugumar Shobana
Published: July 2022

Antibiotic resistance is becoming a threat to the medical industry in treating microbial infections. Many organisms are acquiring antibiotic resistance because of the continuous use of the same drug. Gram-negative organisms are developing multi-drug resistance properties (MDR) due to chromosomal level changes that occurred as a part of evolution or some intrinsic factors already present in the organism. Stenotrophomonas maltophilia falls under the category of Multidrug-Resistant organism. WHO has also urged to evaluate the scenario and develop new strategies for making this organism susceptible to otherwise resistant antibiotics. Using novel compounds as drugs can ameliorate the issue to some extent. The beta-lactamase enzyme in the bacteria is responsible for inhibiting several drugs currently being used for treatment. This enzyme can be targeted to find an inhibitor that can inhibit the enzyme activity and make the organism susceptible to beta-lactam antibiotics. Plants produce several secondary metabolites for their survival in adverse environments. Several phytoconstituents have antimicrobial properties and have been used in traditional medicine for a very long time. The computational technologies can be exploited to find the best compound from many compounds. Virtual screening, molecular docking, and dynamic simulation methods are followed to get the best inhibitor for L1 beta-lactamase. IMPPAT database is screened, and the top hit compounds are studied for ADMET properties. Finally, four compounds are selected to set for dynamics. After all the computational calculations, Withanolide R is found to have a better binding and forms a stable complex with the protein. This compound can act as a potent natural inhibitor for L1 beta-lactamase.
Study protocol for validation of the safety and efficacy of topical steroid therapy targeting nasal-associated lymphoid tissue in IgA nephropathy ﻿: a single-centre, open-label, historical controlled study
Authors: Lee Mingfeng , Suzuki Hitoshi , Kato Rina , Nakayama Maiko , Fukao Yusuke , Kano Toshiki , Makita Yuko , Kobayashi Takashi , Sato Daisuke , Kihara Masao , Nojiri Shuko , Suzuki Yusuke
Published: July 2022

Background
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Approximately 30–40% of patients progress to end-stage renal disease over 20 years. Mucosal immune dysregulation in nasal-associated lymphoid tissue (NALT) may be involved in the pathogenesis of IgAN. In Japan, the efficacy of tonsillectomy combined with steroid pulse therapy (TSP) has been reported. Meanwhile, the risk of surgery i.e., tonsillectomy and the adverse effects related to systemic steroid administration are major concerns for TSP. To overcome these problems, we propose a topical steroid therapy targeting NALT. This therapeutic concept is a novel approach to regulate the mucosal immunity of NALT. In this study, we aim to evaluate the safety and efficacy of dexamethasone-based elixir gargling in patients with IgAN.
Methods
This will be a single-centre, open-label, historical controlled study. We plan to enroll 20 patients diagnosed with IgAN who were scheduled to undergo tonsillectomy. All participants are required to sign a written consent form. The study protocol has been reviewed and approved by Juntendo University Hospital Certified Review Board (CRB3180012). Patients will receive steroid gargling therapy with 10 ml of 0.01% undiluted solution of dexamethasone elixir four times per day for 4 weeks. The primary endpoint is the safety of steroid gargling, including the incidence of adverse events (oral/pharyngeal discomfort and taste disorders), presence of elevated inflammatory markers and presence of glucose intolerance. The secondary endpoint is the efficacy of steroid gargling, including serum IgA and galactose-deficient IgA1 (Gd-IgA1) level, renal function, proteinuria and haematuria. All statistical analyses will be conducted using the SAS statistical software (version 9.4, SAS Institute, Cary, NC, USA).
Discussion
There are few reports of intra-oral, topical steroids in renal disease. Once the steroid gargle is evaluated as safe in this study, extending the gargling period for longer term—for example 3 to 6 months—would be considered in the subsequent large-scale study. This pilot trial would also help in assessing the financial, technical, administrative, or logistic feasibility of a larger study.
Trial registration number
Japan Registry of Clinical Trials (jRCTs031200127). https://jrct.niph.go.jp/latest-detail/jRCTs031200127. Protocol version: October 15, 2021 Ver. 1.3. The date of registration 09/23/2020
Increased Macrophage-like Cell Density in Retinal Vein Occlusion as Characterized by Swept-Source Optical Coherence Tomography Angiography
Authors: Wang Wenyu , Sun Gongpeng , He Lu , Chen Changzheng
Published: July 2022

Objectives: To quantitatively analyze macrophage-like cells (MLCs) at the vitreoretinal interface in retinal vein occlusion (RVO) using swept-source optical coherence tomography angiography (SS-OCTA).Methods: The study included 72 RVO patients, with 43 acute patients and 29 chronic patients. For a normal control, 64 fellow eyes were included. MLCs were visualized in a 5μm en face OCT slab above the vitreoretinal interface centered on the fovea. After semi-automatic binarization and quantification, we evaluated the MLC count and density among groups. We also investigated the MLC density and distribution relative to retinal edema.Results: Morphological changes and congregation of MLCs appeared in RVO eyes. The MLC density of both the acute and chronic groups was significantly higher than that of the control eyes (p<0.001). In the acute group, the MLC density of the edematous region was lower than both the non-edematous region (p<0.001) and the whole image (p<0.01). The MLC density in acute eyes was negatively correlated to central fovea thickness (CFT) (r=-0.352, p<0.05). The MLC density in chronic eyes was positively correlated to CFT and mean retina thickness (MRT) (r=0.406, P<0.05; r=0.412, P<0.05, respectively).Conclusions: SS-OCTA is a viable and simple method for the characterization of MLCs at the vitreoretinal interface. A significant increase in the MLC density in both acute and chronic eyes implicates the activation and recruitment of MLCs in RVO and that the MLC density and distribution can be affected by retinal edema.
Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease among 948,263 individuals ≥65 years of age: A Danish cohort study
Authors: Nielsen Katrine Finderup , Nielsen Lise Birk , Lomholt Frederikke Kristensen , Slotved Hans-Christian , Dalby Tine , Fuursted Kurt , Jørgensen Charlotte Sværke , Valentiner-Branth Palle
Published: July 2022

This study aimed to estimate the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) against invasive pneumococcal disease (IPD) among individuals ≥ 65 years of age. We used Danish nationwide databases to obtain information on PPV23 vaccination, covariates and IPD, and linked data on an individual-level using a unique personal identifier. A total of 948,263 individuals were included and followed between June 15, 2020 and September 18, 2021 (58.6% were vaccinated during follow-up). The adjusted vaccine effectiveness was 42% (95% confidence interval (CI): 9%-63%) for all-serotype IPD and 58% (95% CI: 21%-78%) for PPV23-serotype IPD, using no vaccination as the reference.
Polycyclic aromatic hydrocarbons (PAHs) in fruit juice samples: a health risk assessment study
Authors: Naghashan Mahsa , Kargarghomsheh Pegah , Nazari Roshanak Rafiei , Mehraie Abbas , Tooryan Fahimeh , Shariatifar Nabi
Published: July 2022

The objective of the present research was to investigate the level of 16 PAHs in fruit juice samples (orange, apple, peach, pineapple, and mango) with three different packages (PET bottle, Tetra Pak and Canned packaging) by using MSPE/GC–MS (magnetic solid-phase extraction and gas chromatography-mass spectrometry) method. Our outcomes showed the mean of total PAHs and PAH4 (in all samples) were 7.67 ± 3.19 and 0.37 ± 0.16 µg/L, respectively. The mean of BaP in samples was )0.06 ± 0.03 µg/L( lower than the standard level of US-EPA (0.2 µg/L in drinking water). Also, our results showed that pineapple juice had a maximum mean of total PAHs of 12.42 ± 4.84 µg/L and mango juice had a minimum mean of total PAHs of 5.17 ± 1.24 µg/L. Additionally, canned packaging had a maximum average total PAH of 10.62 ± 5.22 µg/L and PET bottles had a minimum average total PAH of 5.25 03 2.03 µg/L. A heat map approach was also used to cluster samples. The Monte Carlo outcomes indicated that the estimated daily intake (EDI) rank order was Na > B(g)P > Ch > I(cd)P > B(b)F > Ph > B(k)F > F > Ace > Fl > B(a)P > B(a)A > P > A. The Monte Carlo Simulation (MCS) results showed the incremental lifetime cancer risk (ILCR) at the 95th percentiles for adults and children was 4.91E-7 and 9.12E-7, respectively, which indicated no risk (< 10− 6).
Exosomes derived from cancer-associated fibroblasts promote tumorigenesis, metastasis, chemoresistance of colorectal cancer cells by upregulating circ_0067557 to target Lin28A and Lin28B
Authors: Yu Zhiwei , Yang Cheng , Zhang Yan , Yu ZhiWei , Wang Jiahao , Wang Jiaming , Wang Muhong , Xuan Yuhong , Cheng Haiyue , Ma Jiaao , Chai Cuicui , Li Mingzhe
Published: July 2022

Exosomes derived from cancer-associated fibroblasts (CAFs) may be crucial in colorectal cancer (CRC) progression, although the underlying function and mechanism of CAF-derived exosomes in CRC are still unclear. We used a circular RNA (circRNA) array to identify differentially expressed circRNAs in exosomes from normal fibroblasts (NFs) and CAFs. One differentially expressed circRNA was circ_0067557, whose expression was verified by RT-qPCR. The target genes of circ_0067557 (Lin28A and Lin28B) were identified by RNA-pull down, RNA-IP, and RNA-EMSA. The biological behavior of CRC cells and CRC xenograft tumors were examined by multiple assays. Circ_0067557 expression in exosomes from CAFs was higher than in exosomes from NFs. Functionally, CAF-derived exosomes could induce proliferation, migration, invasion, chemoresistance, EMT, and the cancer stem cell (CSC) features of CRC cells while suppressing apoptosis. In addition, we confirmed that circ_0067557 could bind to its target genes (Lin28A and Lin28B). Silencing of circ_0067557 prevented the malignant phenotype of the CRC cell by targeting Lin28A and Lin28B. Moreover, CAF-derived exosomes enhanced the growth of CRC xenograft tumors, suppressed apoptosis, and upregulated Lin28A and Lin28B through circ_0067557. Circ_0067557/Lin28A and Lin28B signal axis may be a potential therapy target for CRC patients.
How Climate, Landscape and Economical Changes Increase the Exposure of Echinococcus Spp.
Authors: Di Xiaoyu , Li Shuo , Ma Bin , Di Xiaofan , Li Yuhao , An Bei , Jiang Wenwen
Published: July 2022

Background: Echinococcosis is a global enzootic disease influenced by different biological and environmental factors. We investigated do and patient populations, and climatic and environmental factors affecting the distribution of Echinococcosis in Gansu Province, China. The risk to people in urban areas is increasing with climate, landscape, and lifestyle changes.Methods: We conducted a retrospective descriptive study using hospitalization case data (2000 to 2020) in Lanzhou. All hospital discharges with echinococcosis diagnosis placed in the first diagnostic position were analyzed, and clinical characteristics were described. We mapped the addresses of 626 hospitalized echinococcosis patients and distribution dogs and studied the effects of different temperature models, mean annual rainfall and slope, latitude, land covers, closeproximity to travel routes, livestock, and dog densities on the occurrence of echinococcosis using a geographical information systems approach. The spatial and temporal distribution of patient epidemiological data combined with infected dog fecal incidence from the scientific literature was also evaluated. We assessed model performance and variable importance to discover the relation of these variables to the exposure of the Echinococcus spp. niche. Then, we imported the resulting niche model into future global Shared Socioeconomic Pathways scenarios.Results: The average cost of treating a case of echinococcosis in Gansu Province was $24,370.2 and showed an increasing trend during the study period. The cost of treating a case of echinococcosis in different counties was significantly negative with their corresponding gross domestic product (GDP). The three factors with the strongest correlation to echinococcosis infection probability were (1) GLC (56.6%), (2) annual precipitation (Bio12, 21.2%), and (3) mean temperature of the Wettest Quarter (Bio12, 8.5% of variations). The risk map showed that areas characterized by Echinococcus spp were mainly located east southern Gansu Province with the highest probability, followed by areas in the center of Gansu Province. When comparing the possible future distribution with the present distribution of Echinococcus spp., an increasing tendency was observed in the highly suitable areas of Echinococcus spp., indicating that environmental changes would affect the distribution of Echinococcus spp.Conclusion: This study provides valuable information for cost-effective public health programs to control echinococcosis in Gansu Province and elsewhere. Raising travelers’ disease awareness and preventive health habits is an urgent agenda and most efficient-reaching action with a small investment.
Stress fracture of ipsilateral femoral neck after total knee replacement: 2 cases report
Authors: Liu Changjie , Liu Xiaoguang , Fu Daotong , Liu Zezhong , Shen Xiaoru , Zhang Yimin
Published: July 2022

The main complications after total knee replacement were pain, infection, thrombosis and nerve injury, but few patients had ipsilateral femoral neck fractures, which might be related to changes of the biomechanical axis of the knee joint, increasing activity level, osteoporosis, and high BMI, following TKR.
Crystal-Modeler: A Tool for Geometric Analysis and Three-Dimensional Modeling of Crystal Forms Based on Rectangular Coordinates in Space
Authors: Chao Huixia , Li Yue , Yao Weihua , Han Xin , Wang Ran
Published: July 2022

Various classification methods have been developed for geometric form of crystals. One method involves the generation of three-dimensional (3D) models of crystals, mainly through graphical representations. However, traditional graphical representations depend on symmetrical operations of crystal planes and the use of polar stereographic projections. There is still very few geometric analysis or mathematical expression for the rectangular coordinate system, meaning that 3D visualization of crystal forms is limited. In this paper, we present a geometric analysis that allows 3D visualization analysis of crystal forms and identifies geometric relations between crystal forms. We divide crystal models in a 3D rectangular coordinate system within 47 types of geometric form into the tetrahedron, polygon (polyhedron), and cube classes. We determine the vertex space coordinates of the 47 types of crystal form through geometric analysis and coordinate calculation of the crystal forms. Last but not least, in order to obtain 3D models of every geometric form under the automorphism of crystals, it is the convex envelope geometric polyhedron algorithm to be created to calculate the edges and triangular faces by WebGL technology which makes it possible to develop an online interactive 3D crystallographic study system in a web-browser.
Longevity of metal-ceramic single crowns cemented with self-adhesive resin cement: An update of a prospective analysis with up to 106 months of follow-up
Authors: Machry Renan Vaz , Bergoli César Dalmolin , Schwantz Julia Kaster , Brondani Lucas Pradebon , Pereira-Cenci Tatiana , Pereira Gabriel Kalil Rocha , Valandro Luiz Felipe
Published: July 2022

Objectives: To evaluate longevity of metal-ceramic single crowns cemented using a self-adhesive resin cement in a prospective clinical analytical study. Methods: A total of 152 teeth received resin composite prosthetic cores and metal-ceramic crowns cemented with a self-adhesive resin cement. The patients included in the sample were recalled for clinical and radiography evaluation in an up-to-106-month period after the final cementation procedures, with an average of 62 months of follow-up. Next, 93% of the sample (142 teeth) were evaluated regarding the treatment survival rate, analysed considering the loss of crown retention (crown debonding) as the primary outcome. In addition, post debonding, root fracture and tooth loss occurrences were also recorded as secondary outcomes to evaluate the success rate of the prosthetic treatment. The aesthetic parameters were also evaluated according to the FDI criteria. The Kaplan-Meier method and Cox regression, with 95% confidence interval was applied for the statistical analysis. Results: Regarding the primary outcome, the metal-ceramic crowns cemented with self-adhesive resin cement presented a high survival rate (93%), with 8 crown debondings occurring after the evaluation period. For secondary outcomes, 9 root fractures, 4 post debondings and 3 tooth losses (1 due to caries and 2 due to periodontal disease) occurred, generating a success rate of 72%. All crowns had a score 1 on the FDI criteria, indicating that they were clinically excellent or very good regarding the aesthetic parameters.Conclusion: The metal-ceramic crowns luted with a self-adhesive resin cement presented a survival rate of 93% after an average follow-up of 62 months. Furthermore, the restorations remained aesthetically satisfactory over time, without changes that would indicate prosthetic retreatment. A success rate of 72% was obtained considering the secondary outcome, mainly related to intraradicular retainer failures (root fractures or post debonding). Clinical Significance: The self-adhesive resin cement is clinically indicated for cementation of metal-ceramic crowns.
Knowledge of necrophagous insects by justice actors and traditional gravediggers for their application in criminal investigations in the northern and southern Sudanese zones of Burkina Faso
Authors: Zongo David , Drabo Samuel Fogné , Séré Aminata , Romba Rahim , Bougma Adjima , Millogo Missa , Salou Noufou , Zeba Moctar , Kinda Prosper , GNANKINE Olivier
Published: July 2022

Forensic entomology is used in criminal investigations for post-mortem dating of cadavers. The aims of this study was to evaluate the endogenous knowledge of necrophagous insects of six target groups of workers in two climatic zones of Burkina Faso for their application in criminal investigations. The survey was conducted among 223 informants splited in six target groups in four cities and eight villages belonging to Sudano-Sahelian and Sudanian climatic zones. The study was conducted on the knowledge of necrophagous insects from exhumed and exposed corpses to the air. Chi-square tests and principal component analysis (PCA) were performed to check for species diversity distributions significant differences in knowledge and climatic zones of study. The different phases of insect succession on post-mortem corpses were cited. The results showed that knowledge of the species varies from one species to another. The most cited species are Calliphoridae larvae and pupae with a frequency of citation of 16.54% for open corpses Astrapaeus sp. with a frequency of citation of 32.25% for exhumed corpses. The citation of species also varied according to locality climatic zone and function of the informants. Traditional gravediggers and funeral workers cited more species than other justice actors. The species of Chrysomya sp. and Lucilia sp. are species found to be specific to the West African area and were mentioned for the first time in Burkina Faso. The knowledge of necrophagous insects by the informants in this survey opens new perspectives for entomological expertise in criminal investigations in Burkina Faso.
Design of inherent fire retarding and degradable bio-based epoxy vitrimer with excellent self-healing and mechanical reprocessability
Authors: Yang Weijun , Ding Hui , Zhou Wei , Liu Tianxi , Xu Pengwu , Puglia Debora , Kenny Jose M , Ma Piming
Published: July 2022

Epoxy resin possesses poor flame retardancy and difficulty in both recycling and reprocess ability that largely limit its application. Herein, two vanillin based epoxy monomers, shorted as VAD-EP (A) and VDP-EP (P), containing both imine bonds and inherently fire retarding phosphorus elements, were synthesized via in situ condensation reaction with DDM and addition reaction with DOPO, followed by the epoxidation by epichlorohydrin. Epoxy vitrimer materials were then cured by D230 diamine hardener by adjusting the proportion of VAD-EP and VDP-EP monomer. When the mass ratio of VAD-EP and VDP-EP was 8:2, A8P2-D230 reached the fire retarding UL-94 V0 rating and LOI value of 27.0% with only 0.66% of phosphorus content, this behavior was ascribed to condensed phase and free radical scavenging mechanisms. When the mass ratio was 7:3, the tensile strength and elastic modulus of the A7P3-D230 epoxy were 75.5 MPa and 2.5 GPa, respectively, i.e. 48.6% and 18.8% higher than A10P0-D230 sample. Meanwhile, the material showed high stress relaxation rate, due to the presence of dynamic imine bonds in the topological crosslinking network. As a consequence, the epoxy vitrimer exhibited excellent self-healing capability, reprocessability and degradation behaviors. The biobased epoxy vitrimer was then used to prepare the carbon fibers (CFs) reinforced epoxy composites, results showed that CFs can be completely recycled. Interestingly, the recycled CFs maintain unchanged chemical structure, mechanical properties and morphology as the original CFs.
Effectiveness of laparoscopic tubal anastomosis in tubal ligation patients, A retrospective study
Authors: Ding Nan , zhang Jian , Wang peili , Wang Fang
Published: July 2022

Objective
To evaluate the pregnancy outcome after laparoscopic tubal anastomosis and to analyze the factors that may affect the pregnancy outcome.
Methods
This study was a retrospective analysis of pregnancy outcomes in 82 patients with a history of tubal sterilization treated with laparoscopic tubal anastomosis at the Lanzhou University Second Hospital Reproductive Medicine from July 2017 to December 2021. The primary outcomes were intrauterine pregnancy, ectopic pregnancy, miscarriage. We also examined relevant factors that may influence pregnancy status.
Results
The cumulative clinical pregnancy rate for all patients was 52/81 (63.61%). The distribution of pregnancy outcomes for the whole group was as follows: intrauterine pregnancy rate, 49/81 (59.75%), ectopic pregnancy rate, 3/82 (3.66%) and miscarriage rate, 5/81 (6.10%). In the multivariate model, age, pelvic adhesions, and endometrial polyps may be the main prognostic factors.
Conclusion
Laparoscopic tubal anastomosis is an effective treatment for patients with tubal-related infertility, especially for women under 40 years.
Enabling Data-Limited Chemical Bioactivity Predictions through Deep Neural Network Transfer Learning
Authors: Liu Ruifeng , Laxminarayan Srinivas , Reifman Jaques , Wallqvist Anders
Published: July 2022

The main limitation in developing deep neural network (DNN) models to predict bioactivity properties of chemicals is the lack of sufficient assay data to train the network’s classification layers. Focusing on feedforward DNNs that use atom- and bond-based structural fingerprints as input, we examined whether layers of a fully trained DNN based on large amounts of data to predict one property could be used to develop DNNs to predict other related or unrelated properties based on limited amounts of data. Hence, we assessed if and under what conditions the dense layers of a pre-trained DNN could be transferred and used for the development of another DNN associated with limited training data. We carried out a quantitative study employing more than 400 pairs of assay datasets, where we used fully trained layers from a large dataset to augment the training of a small dataset. We found that the higher the correlation r between two assay datasets, the more efficient the transfer learning is in reducing prediction errors associated with the smaller dataset DNN predictions. The reduction in mean squared prediction errors ranged from 10–20% for every 0.1 increase in r2 between the datasets, with the bulk of the error reductions associated with transfers of the first dense layer. Transfer of other dense layers did not result in additional benefits, suggesting that deeper, dense layers conveyed more specialized and assay-specific information. Importantly, depending on the dataset correlation, training sample size could be reduced by up to 10-fold without any loss of prediction accuracy.
Single irrigation at the four-leaf stage in the spring optimizes winter wheat water consumption characteristics and water use efficiency
Authors: Bao Xiaoyuan , Liu Xuejing , Hou Xiaoyang , Yin Baozhong , Duan Weiwei , Wang Yandong , Ren Jianhong , Gu Limin , Zhen Wenchao
Published: July 2022

Water scarcity is a major limiting factor for crop production in North China Plain (NCP), which produces the majority of the country's winter wheat (Triticum aestivum L.). The objective of this three-year field study was to see if and when irrigation one-time in spring improves grain yield and water use efficiency. Four sets of irrigation were established at the 3-leaf visible stage (L3) and the L4, L5, and L6 stages. The spike number, 1,000-grain weight, and water consumption increased progressively when irrigation time was delayed, whereas grain yield, grain number, dry matter, harvest, and WUE grew, then dropped, and peaked at L4. The increased grain number can be attributed to the L4's higher daily water consumption and water consumption percentage than the L3, L5, and L6 at the jointing-anthesis stages. L4 had a shorter cumulative period of soil drought stress (37 days), whereas L3, L5, and L6 had 40, 42, and 43 days, respectively. Furthermore, flag leaf senescence was postponed in L4 with a better post-anthesis leaf area index, photosynthetic rate, chlorophyll content, stronger superoxide dismutase activity, and reduced malondialdehyde concentration. As a result, single irrigation at the 4-leaf visible stage optimized water deficit and consumption before and after anthesis, resulting in higher yield and WUE in the NCP.
The influence of extremely high body weight (BMI > 35kg/ m2) on apixaban plasma concentration in patients with atrial fibrillation
Authors: Hilu May , Colodner Raul , Eitam Harel , Avraham Gilat Ron , Ram Kerstin Carlin , Elias Mazen , Shimoni Orli , Schwartzberg Eyal , Goldstein Lee Hilary
Published: July 2022

Apixaban, a direct oral anticoagulant (DOAC) is administered in a fixed-dose regimen for atrial fibrillation patients. Dosage adjustment is based on renal function, age, and body weight (less than 60 kg). No data exist on the pharmacokinetics of apixaban in patients with body mass index (BMI) ≥ 35 Kg/m2, nor about treatment efficacy and safety in this population. Aims: To reveal whether BMI ≥ 35 kg/m2 affects trough plasma concentrations of apixaban in patients with atrial fibrillation and whether dose adjustment is required in this population. Methods: This prospective study compared steady state trough concentrations of apixaban in patients with BMI ≥ 35 kg/m2 and patients with BMI < 35 kg/m2. Results: Sixty patients were included in the study. In patients on 5 mg twice daily dose, the median trough plasma concentration was 29% lower in the high BMI group (BMI ≥ 35 kg/m2) compared with the lower BMI group (BMI < 35 kg/m2) (148.9 ng/ml, IQR: 94.5-205.6, compared to 209.1 ng/ml IQR: 167- 266.8 ng/ml respectively). P = 0.044. However, median trough concentrations were within the manufactures predicted steady-state apixaban exposure range. A similar trend was found among patients treated with 2.5 mg apixaban twice daily, but the results did not reach statistical significance. According to multivariate analysis performed, no correlation was found between BMI values (neither BMI ≥ 35 kg/m2 nor BMI < 35 kg/m2) and trough concentrations. Conclusion: Lower apixaban trough concentration was observed in patients with BMI ≥ 35 kg/m2 but remains within the steady-state apixaban exposure range found to be effective according to manufacturer data.
Testing the effects of perceptual grouping on visual search in older adults
Authors: Lai Sung-Nan , Jingling Li
Published: July 2022

Visual search is to find targets while ignoring distractors. Previous studies established that a target is more difficult to identify if aligned collinearly with other items, called the collinear search impairment. Since older adults have lower perceptual grouping ability than younger adults, benefits in visual search may occur for older adults for they may be less distracted by the collinear distractors. Three experiments were carried out to compare 45 younger and 45 older healthy adults. Participants were asked to identify a target either overlapping or non-overlapping with a collinear distractor, and the response difference between the two conditions is the collinear search impairment. Results showed that both groups showed reliable search impairment specific to collinear distractor regardless of grouping difficulty and task demands, and the impairment strength increased with the grouping strength of the collinear distractor. Further analysis revealed that the response times of older adults increased in a multiplicative manner to that of younger adults, suggesting that longer response of older adults spread to multiple underlying processing including grouping and suppression of collinear distractors. Together, the results suggest that older adults were still distracted in visual search even when grouping was required on a distractor. Our findings also highlight how general slowing may delay suppression processing in visual search.
oxLDL promotes EMS-induced angiogenesis by up-regulating VEGF-A expression and secretion of endometrial cells
Authors: Ma Caiqi , Huang Wei , Wang Hui , Yao Wenxia , Liang Min , Yu Guifang , Zhou Xinke
Published: July 2022

Background
Endometriosis (EMS) is a "tumor-like" gynecological disease with distant metastasis, and studies have shown that EMS can carry out distant metastasis through vascular vessels, but the driving factor and its mechanism is not clear.
Methods
We use EMS animal model and gene knockout technique to explore the role of EMS-induced angiogenesis in EMS metastasis in vivo and in vitro, and clarify the role and molecular mechanism of oxLDL in promoting EMS induced angiogenesis.
Results
We found that microvascular density (MVD) in metastasized ectopic endometrium and eutopic endometrial tissue were higher than the normal endometrial tissue, and the plasma oxLDL was positively correlated with the distant metastasis of EMS. Furthermore, we clarify that oxLDL enhanced the MVD of endometrial tissue by up-regulating the VEGF-A expression and secretion in endometrial cells. At last, we illustrated the mechanism of oxLDL promoting the VEGF-A expression through the AKT-HIF-1α signaling pathway.
Conclusion
oxLDL is a risk factor promoting the EMS distant metastasis by up-regulating VEGF-A expression and secretion through AKT-HIF-1α signaling. This founding may provide theoretical support and therapeutic targets for the clinical prevention and treatment of EMS.
Evaluation of a Pilot, Community-Led Mental Illness De-stigmatization Theater Intervention in Rural Uganda
Authors: Lee Yang Jae , Rauben Kazungu , Liu Curtis , Kim Rebecca , Velde Nina van der , Taylor Chelsea , Walsh Alyssa , Asasira Mildred , Katongole Ivan , Hatfield-King Jolee , Blackwell Scott , Iheanacho Theddeus , Christ Ryan , Ssekalo Ibrahim
Published: July 2022

Background
In rural areas of low- and middle- income countries (LMICs), mental health care is often unavailable and inaccessible, and stigma is a major barrier to treatment. Destigmatization can increase treatment-seeking attitudes, community support, and acceptance of mentally ill individuals. This study’s primary objective was to evaluate the impact of a community-led, theater-based destigmatization campaign for mental illness conducted in the Busoga region of Eastern Uganda.
Methods
One hundred residents of the Busoga region were randomly selected via cluster sampling to complete a structured questionnaire assessing mental health stigma. Common misconceptions and points of stigma were identified from these responses, and local village health team personnel (VHTs) developed and performed a culturally-adapted theatrical performance addressing these points. Changes in perceptions of mental illness were measured among 57 attendees using two measures, the Broad Acceptance Scale (BAS) and Personal Acceptance Scale (PAS), before and after the performance.
Results
There was a significant increase in acceptance according to the BAS (p < .001) and PAS (p < .001). Qualitative responses from play attendees also indicated a decrease in stigma and an increased sense of the importance of seeking treatment for mentally ill patients.
Conclusions
This study shows community-led, theater intervention may be an effective tool for the destigmatization of mental illness in rural areas of Uganda. Further, larger studies are needed to test its effectiveness, and potential for scale up and sustainment.
E-scooter Related Facial Injuries- A One Year Review Following Implementation Of A Citywide Trial
Authors: Sritha Rajeevan , Blore Christopher , Arya Richa , McMillan Kevin
Published: July 2022

ObjectiveBirmingham City Council commenced e-scooter trials from September 2020 as part of the wider UK effort to introduce E-scooters as an alternative method of transport. Our aim was to review and evaluate maxillofacial injuries in the initial trial period of 1-year and comment on the safety implications.MethodThe Queen Elizabeth Hospital is a level 1 Major Trauma Centre and the hub for maxillofacial services in Birmingham, UK. A single-center retrospective study captured patients who sustained e-scooter related facial injuries in the Birmingham e-scooter trial period from September 2020 to September 2021.ResultsA total of 29 patients were identified as having facial injuries. 59% (n=17) of patients were male and aged under 30. 43% (n=18) of all injuries recorded involved hard tissue. 41% (n=12) of patients were recorded to be under the influence of alcohol or cannabis. The non-use of helmets was recorded at 34% (n=10) of patients. 20 patients were managed operatively. 100% of patients (n=12) that were under the influence of drugs or alcohol required operative management.ConclusionWith the introduction of the trials, it is shown that facial injuries represent a sizeable proportion of all injuries. It is clear that e-scooters have significant safety issues. Our study may influence legislation to account for improvements in users’ compliance to safety measures and enforcement of those using e-scooters illegally. Legislation regarding the future of E-scooters is expected from the Department of Transport (UK) in March 2022.
Mental imagery content is associated with disease severity and specific brain functional connectivity changes in patients with Parkinson’s disease
Authors: Cherry Jared Michael , Kamel Serageldin , Elfil Mohamed , Aravala Sai Sudha , Bayoumi Ahmed , Patel Amar , Sinha Rajita , Tinaz Sule
Published: July 2022

ABSTRACT
Mental imagery is the mental re-creation of perceptual experiences, events and scenarios, and motor acts. In our previous study, we assessed whether motor imagery (MI) training combined with functional magnetic resonance imaging-based neurofeedback could improve the motor function of nondemented subjects with mild Parkinson’s disease (PD) (N=22). We used visual imagery (VI) (e.g., of scenes or events, but not of self-movements) training without neurofeedback for the control group (N=22). Notably, both groups showed significant and comparable improvement in motor function after four weeks of daily imagery practice. In this study, we further examined the neural correlates of the motor enhancement as a result of the VI training by analyzing the self-reported VI content during daily practice and relating its quality to the functional connectivity characteristics of the same subjects. We demonstrated that the VI practice encompassed multisensory, spatial, affective, and executive processes all of which are also important for motor function in real life. Subjects with worse global disease severity also showed poorer quality of the VI content. Finally, the quality of the VI content showed significant positive correlations with the functional connectivity changes during the VI tasks in brain areas supporting visuospatial and sensorimotor processes. Our findings suggest that mental imagery training combining VI and MI may enhance motor function in patients with mild PD, and more broadly, underline the importance of incorporating self-reports of thoughts and experiences in neuroimaging studies that examine the brain mechanisms of complex cognitive processes especially in neuropsychiatric patient populations.
Vegetation Assessments Under the Influence of Environmental Variables; A Case Study from the Yakhtangay hill of Himalayan range, Pakistan
Authors: Khan Hameed Ullah , Khan Shujaul Mulk Khan , Khan Zahid Ullah , Khan Zeeshan Ahmad , Jahangir Sadia Jahangir
Published: July 2022

The interrelationship between vegetation and abiotic variables inside an ecosystem is one of the main jobs of plant scientist. This study was designed to investigate the vegetation structure and species diversity along the environmental variables in the Yakhtangay hill district Shangla of the Himalayan Mountain series Pakistan, by using multivariate statistical analysis. Quadrat’s method was used and a total of 171 Quadrats were laid down 57 for Tree, Shrubs and Herbs respectively, to analyze the phytosociological attributes of the vegetation. The vegetation of the selected area was classified into different Life and leaf forms according to Raunkiaer classification, while PCORD software version 5 was used to classify the vegetation into different plants communities by Two-way indicator species Analysis (TWINSPAN). The CANOCCO version 4.5 was used for DCA and CCA analysis to find out variation directories of vegetation with different environmental variables. A total of 114 plants species belonging to 45 different families was investigated inside the area. The Rosaceae was the dominant family followed by Poaceae and then Asteraceae. Monocots were dominant than Dicots and Angiosperms were dominant than Gymnosperms. Among the life forms the Hemicryptophytes and Nanophanerophytes were dominant followed by Therophytes, while among the leaf forms Microphylls were dominant followed by Leptophylls. It is concluded that among the edaphic factors such as soil pH, the concentration of soil organic matter, Calcium Carbonates concentration in soil, soil EC, soil TDS, and physiographic factors such as Altitude and slope are affecting the structure of vegetation, species composition and species diversity at the significant level with p-value ≤ 0.05. The Vegetation of the selected area was classified into four major plants communities and the indicator species for each community was recorded. Classification of plants into 4 different communities based upon edaphic gradients favors the individualistic hypothesis. Indicator Species Analysis (ISA) shows the indicators of the study area are mostly indicators to the Himalayan or moist temperate ecosystem, furthermore these indicators could be considered for micro-habitat conservation and respective ecosystem management plans.
LY294002 attenuates neutrophilic airway inflammation and inhibits NLRP3 inflammasome activation in an OVA-LPS-induced asthma murine model
Authors: Lv Yunxiang , Jiang Guiyun
Published: July 2022

Background: Existing investigations suggest that the blockade of phosphoinositide 3-kinase (PI3K) activity contributes to inflammatory solution in allergic asthma, but whether this inhibition directly attenuates neutrophilic airway inflammation in vivo is still unclear. We explored the pharmacological effects of LY294002, a specific inhibitor of PI3K on the progression of neutrophilic airway inflammation and investigated the underlying mechanism. Methods and Results: Female C57BL/6 mice were intranasally sensitized with ovalbumin (OVA) together with LPS on days 0 and 6, and challenged with OVA on days 14-17 to establish a neutrophilic airway disease model. In the challenge phase, a subset of mice was treated intratracheally with LY294002. We found that treatment of LY294002 attenuates clinic symptoms of inflammatory mice. Histological studies showed that LY294002 significantly inhibited inflammatory cell infiltration and mucus production. The treatment also significantly inhibited OVA-LPS induced increases in inflammatory cell counts, especially neutrophil counts, and IL-17 levels in bronchoalveolar lavage fluid (BALF). LY294002 treated mice exhibited significantly increased IL-10 levels in BALF compared to the untreated mice. In addition, LY294002 reduced the plasma concentrations of IL-6 and IL-17. The anti-inflammatory effects of LY29402 were correlated with the downregulation of NLRP3 inflammasome. Conclusions: Our findings suggested that LY294002 as a potential pharmacological target for neutrophilic airway inflammation.
Deformation Mechanism of the Zhoujiashan Landslide Under the Combined Effect of Rainfall and Earthquakes in Tianshui, Northwestern China
Authors: REN Jian , SUN Ping , LI Rongjian , WANG Haojie , ZHANG Shuai , ZHANG Jing
Published: July 2022

Tianshui is located in a geomorphologic transitional zone with well-developed tectonics. Two historical earthquakes with magnitudes greater than 7.0 have occurred in Tianshui and its surrounding areas. The strata consist of primarily loess and mudstone, and geological disasters frequently occur. The Zhoujiashan landslide is a historical earthquake landslide that is currently relatively stable. To study its deformation and stability under the combined effect of rainfall and earthquake motion, the landslide was analyzed via field investigations, shaking table tests, and numerical calculations. The fastest responses were those of the pore water pressure and volume water content in the 0.3-m-depth range under rainfall conditions. The rainfall infiltration depth is limited to approximately 2 m and has a minimal impact on the overall stability of the slope. The response to earthquake accelerations increases with increasing elevation, and earthquakes have a significant amplification effect on structures with an inherent period of 0.2–0.4 s. Under 0.1-g and 0.3-g earthquake conditions, the slope deforms and the safety factor decreases but the landslide does not suffer overall failure. Under the 0.6-g earthquake condition, the slope liquefies, leading to the overall failure of the slope. The location of the liquefaction zone in the numerical calculation is in agreement with the actual situation. Under the 0.6-g earthquake condition, the overall failure mechanism of the slope is vibration liquefaction at the sliding surface.
Pregnancy outcome and risk of recurrence after tissue-preserving LOOP Electrosurgical Excision Procedure (LEEP)
Authors: Alena Jule , Mondal Anne , Lieb Lenard , Fehm Tanja Natscha , Hampl Monika
Published: July 2022

Background/Purpose: This study aims to investigate whether women with cervical dysplasia after LEEP have an increased risk of pregnancy/childbirth complications or recurrence of dysplasia in an upcoming pregnancy. Methods: Data from 240 women after LEEP were analysed retrospectively. The reference group consisted of 956 singleton births. Fisher and Wilcoxon rank tests were used to detect differences between groups. Using logistic regressions, we analysed the effect of surgery specific aspects of LEEP on pregnancy/childbirth complications and the frequency of CIN recurrences. Results: We found that tissue preserving LEEP did not lead to premature birth or miscarriage and did not increase the likelihood of CIN recurrence. We did not observe differences regarding preterm birth (< 37 (p < 0.28) < 34 (p < 0.31), < 32 weeks of gestation (p < 0.11)) or birth weight (< 2500g (p < 0.54), < 2000g (p < 0.77) between groups. However, women after LEEP exhibit a higher risk of premature rupture of membranes 2 (PROM) at term (p < 0.009) and vaginal infections (p < 0.06). Neither volume nor depth of the removed tissue nor an additional endocervical resection seem to influence the likelihood of premature birth or early miscarriage. Performing an endocervical resection protects against CIN recurrence (OR = 0.0881, p < 0.003). Conclusions: After tissue-preserving LEEP, there is an increased risk of vaginal infections and PROM at term in consecutive pregnancy. LEEP does not affect prematurity or miscarriage. The removal of additional endocervical tissue appears to be a protective factor against recurrence of CIN.
Factors Associated with EMS On-Scene Time and Its Regional Difference in Road Traffic Injuries: A Population-based Observational Study
Authors: Ito Shingo , Asai Hideki , Kawai Yasuyuki , Suto Shunji , Ohta Sachiko , Fukushima Hidetada
Published: July 2022

Background
The outcome of road traffic injury (RTI) is determined by duration of prehospital time, patient’s demographics, and the type of injury and its mechanism. During the emergency medical service (EMS) prehospital time interval, on-scene time should be minimized for early treatment. This study aimed to examine the factors influencing on-scene EMS time among RTI patients.
Methods
We evaluated 19,141 cases of traffic trauma recorded between April 2014 and March 2020 in the EMS database of the Nara Wide Area Fire Department and the prehospital database of the emergency Medical Alliance for Total Coordination of Healthcare (e-MATCH). To examine the asociation of the number of EMS phone calls until hospital acceptance, age ≥ 65 years, high-risk injury, vital signs, holiday, and nighttime (0:00–8:00) with on-scene time, a generalized linear mixed model with random effects for four study regions was condcuted.
Results
EMS phone calls were the biggest factor, accounting for 5.69 minutes per call, and high-risk injury accounted for an additional 2.78 minutes. Holiday, nighttime, and age ≥ 65 years were also associated with increased on-scene time, but there were no significant vital sign variables for on-scene time except for level of consciousness. Regional differences were also noted based on random effects, with a maximum difference of 2 minutes among regions.
Conclusions
The number of EMS phone calls until hospital acceptance was the most significant influencing factor in reducing on-scene time, and high-risk injury accounted for up to an additional 2.78 minutes. Considering these factors, including regional differences, can help improve the regional EMS policies and outcomes of RTI patients.
Isolation and cloning of sprA gene-producing alkaline protease of Streptomyces flavogriseus ADEM7, and application as an antioxidant and antitumor
Authors: ELHADEDY doaa , safwat nesreen , partila abir
Published: July 2022

The authors have requested that this preprint be removed from Research Square.