bluuebunny/crossref_metadata_2025 huggingface dataset:
Qingwei San Treats Oral Ulcer Subjected to Stomach Heat Syndrome in db/db Mice by Targeting TLR4/MyD88/NF-κB Pathway
Authors: Shi Lu , An Yongcheng , Cheng Long , Li Yiyang , Li Huimin , Wang Chen , Lv Yinglan , Duan Yuhui , Dai Hongyu , He Changhao , Zhang Huilin , Huang Yan , Fu Wanxin , Wang ShengPeng , Zhao Baosheng , Wang Yitao , Zhao Yonghua
Published: November 2021

Background Qingwei San (QWS), one of classic Chinese Medicine prescripts, has been widely used to treat stomach heat syndrome which manifests oral ulcer (OU), periodontitis and upper gastrointestinal bleeding for seven hundred years. However, the therapeutic effects of QWS on diabetic OU subjected to stomach heat syndrome are still ambiguous. In the study, we investigate the pharmacological mechanisms. Methods The main components of QWS aqueous extract were analyzed by LC-MS, and potential pathways of QWS targeting OU were predicted by network pharmacology. The db/db mice were administered with the decoction of dried Zingiber officinale Rosc. rhizome combined with NaOH cauterization to establish the model of diabetic OU subjected to stomach heat syndrome. Subsequently, the model mice were treated with QWS, and OU wound healing status were recorded. The pathological changes of gastric tissue and oral mucosa were evaluated using hematoxylin-eosin staining, and the morphology of collagen fibers in oral mucosa was assessed by Masson staining. The levels of thromboxane B 2 (TXB 2 ), 6-Keto-prostaglandin F1α (6-keto-PGF1α), interleukin-1 β (IL-1β), IL-2, IL-6, tumor necrosis factor-α (TNF-α), β-endorphin (β-EP) and 5-Hydroxytryptamine (5-HT) were determined by ELISA assay. The protein expressions of Toll-like receptor 4 (TLR4), TNF receptor associated factor 6 (TRAF6), myeloid differentiation factor 88 (MyD88), inhibitor of NF-κB alpha (IκΒα), p-IκΒα and nuclear factor kappa-B (NF-κB) p65 were measured by Western Blotting. Results A total of 183 compounds in QWS were identified by LC-MS, and identified 79 bioactive compounds corresponded to 269 targets and 59 pathways. QWS high-dose treatment significantly reduced the level of TXB 2 and the ratio of TXB 2 /6-keto-PGF1α. Meanwhile, it improved mucosal pathological morphology, and reduced the area of OU and local edema. Simultaneously, the levels of TNF-α, IL-1β, IL-6, IL-2 and 5-HT, and the expressions of TLR4、TRAF6、MyD88、p-IκΒα and NF-κB p65 were decreased. Conclusion QWS treatment facilitates the healing of OU, ameliorates pathological morphologies of gastric and oral mucosa and decreases the levels of pro-inflammatory cytokines in db/db mice subjected to stomach heat syndrome, whose mechanism may be associated with the inhibition of TLR4/MyD88/NF-κB signaling pathway to exert anti-inflammatory effects.
Construction of a Convenient Screening Method for P-Hydroxybenzoate Hydroxylase To Enable Efficient Gallic Acid and Pyrogallol Biosynthesis
Authors: Chen Zhenya , Chen Tongtong , Yu Shengzhu , Huo Yi-Xin
Published: November 2021

BackgroundGallic acid (GA) and pyrogallol are phenolic hydroxyl compounds and have diverse biological activities. Microbial-based biosynthesis of GA and pyrogallol has been emerged as an ecofriendly method to replace the traditional chemical synthesis. In GA and pyrogallol biosynthetic pathways, the low hydroxylation activity of p-hydroxybenzoate hydroxylase (PobA) towards 3,4-dihydroxybenzoic acid (3,4-DHBA) limited the high-level biosynthesis of GA and pyrogallol.ResultsThis work reported a high active PobA mutant (Y385F/T294A/V349A PobA) towards 3,4-DHBA. This mutant was screened out from a PobA random mutagenesis library through a novel naked eye visual screening method. In vitro enzyme assay showed this mutant has a kcat/Km of 0.059 μM-1s-1 towards 3,4-DHBA, which was 4.92-fold higher than the reported mutant (Y385F/T294A PobA). Molecular docking simulation provided the mechanism explanation of the high activity. Expression of this mutant in E. coli BW25113 (F’) can generate 830 ± 33 mg/L GA from 1000 mg/L 3,4-DHBA. After that, we utilized this mutant to assemble a de novo GA biosynthetic pathway. Subsequently, this pathway was introduced into a 3,4-DHBA-producing strain (E. coli BW25113 (F’)ΔaroE) to achieve 301 ± 15 mg/L GA production from simple carbon sources. Similarly, assembling this mutant into a de novo pyrogallol biosynthetic pathway enabled 129 ± 15 mg/L pyrogallol production.ConclusionsThis work established an efficient screening method and generated a high active PobA mutant. Assembling this mutant into GA and pyrogallol biosynthetic pathways achieved the de novo production of these two compounds. Besides, this mutant has great potential for GA or pyrogallol derivatives production. The screening method could be used for other GA biosynthesis-related enzymes.
Effects of polycyclic aromatic hydrocarbons on the proliferation and differentiation of placental cells
Authors: Jo Yun Sung , Ko Hyun Sun , Kim Ah Young , Jo Ha Gyeong , Kim Woo Jung , Choi Sae Kyung
Published: November 2021

Background
The purpose of this study was to investigate the effects of polycyclic aromatic hydrocarbons (PAHs) other than bisphenol A (BPA) and BPA substitutes on placental cells.
Methods
HTR-8/SVneo cells were treated with anthracene, benzo[k]fluoranthene, benzo[a]pyrene, endocrine disruptors, and 4,4-(9-fluorenylidene)diphenol, which is used as a substitute for BPA-free products. After confirming the dose response for each reagent using the prepared cells, the cells were incubated for 24, 48, and 72 h. Cell viability was confirmed using the XTT assay. Each experiment was performed with the minimum number of samples (n = 3) required for statistical analysis. The results were analyzed using t-tests; p < 0.05 was considered statistically significant.
Results
After treatment with anthracene, benzo[k]fluoranthene, benzo[a]pyrene, endocrine disruptors, and 4,4-(9-fluorenylidene)diphenol, the absorbance measured using the XTT assay decreased significantly with increasing concentration. The absorbance decreased significantly over time following treatment with each endocrine disruptor at the concentration confirmed by the dose–response analysis.
Conclusions
This study showed that anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol—a BPA substitute—affect cell viability and necrosis in the placental cell line. The study indicates the serious effects of PAHs that negatively affect pregnancy but were previously unknown. Further, this study would serve as a reference for the identification of harmful PAHs during pregnancy prognosis in women who are more susceptible to PAH exposure.
A Novel Pyroptosis-related Genes Prognostic Signature Affects the Immune Infiltration Patterns in Hepatocellular Carcinoma
Authors: Jin Yiqun , Xue-song Bai.
Published: November 2021

PurposePyroptosis is an inflammatory form of cell death associated with tumorigenesis and progression. However, the prognostic value of pyroptosis-related genes (PRGs) in hepatocellular carcinoma (HCC) have not been elucidated.MethodsWe downloaded mRNA expression profiles and clinical information from TCGA and ICGC database. Then, differently expressed PRGs were screened to construct a multigene prognostic signature by least absolute contraction and selection operator (LASSO) Cox regression method in TCGA cohort. Date from ICGC was used to validate the robustness of this signature. Kaplan-Meier analysis was used to compare overall survival (OS) between high- and low-risk group. Univariate and multivariate Cox analysis were performed to identify the independent prognostic value of the signature. Gene set enrichment analysis (GSEA) was utilized to conduct GO and KEGG analysis. Single-sample gene set enrichment analysis was implemented to assess the immune cell infiltration and immune-related function. TIDE algorithm evaluated the significance of this signature in predicting immunotherapeutic sensitivity. ResultsAn 8-PRGs prognostic model was established. The OS of low-risk group was significantly increased compared to high-risk group. Receiver operating characteristic curve showed the model had a good prognostic predictive accuracy. Cox regression analysis proved the model an independent predictor for OS in HCC. GSEA indicated that the risk score was associated with immune response. Furthermore, different subgroups exhibited different immunoinfiltration patterns, different immune-checkpoint levels and different potential responses for immune-checkpoint blockade therapy.ConclusionAn 8-PRGs signature can predict the prognosis of HCC patients and may act as an immunotherapeutic potential target for HCC.
Biochemical Targets and Molecular Mechanism of Ginsenoside Compound K for Treating Osteoporosis Based on Network Pharmacology
Authors: Zhang Sen , Shen Shihong , Ma Pei , Fan Daidi
Published: November 2021

Ginsenosides have been proven to be potential beneficial in treatment of osteoporosis. To investigate the potential of ginsenosides in osteoporosis, ginsenoside compound K (GCK) was selected to explore the potential therapy targets and mechanism based on network pharmacology (NP). 206 and 6590 targets were obtained for GCK and osteoporosis, respectively, in which 138 targets were identified as co-targets of GCK and osteoporosis based on intersection analysis. Five central gene clusters and hub genes (STAT3, PIK3R1, VEGFA, JAK2 and MAP2K1) were identified through protein-protein interaction network analysis. Gene Ontology (GO) enrichment implied that phosphatidylinositol-related biological process, molecular modification and function may play an important role for GCK in treatment and prevention of osteoporosis. Functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that 16 targets were enriched in the osteoclast differentiation. Also, except for being identified as hub targets, MAPK and phosphatidylinositol-related proteins were enriched in the downstream signaling of c-Fms in the osteoclast differentiation pathway. Molecular docking further confirmed that GCK could interact with active cavity on the surface of c-Fms (osteoclast differentiation-related membrane receptor), and their complex could be stabilized by three H-bonds with residues including Glu 664 (3.19 Å), Glu 664 (2.62 Å) and Cys 666 (2.78 Å). Summarily, GCK could interfere the occurrence and progress of osteoporosis through c-Fms-mediated MAPK and phosphatidylinositol-related signaling regulating osteoclast differentiation.
Lateral Trans-Malleolar Approach for Posterior Malleolar Fractures of the Ankle for Articular and Syndesmosis Reduction : A Retrospective Study
Authors: Taki Masanori , Suzuki Kosuke , Hio Naohiro , Hasegawa Atsushi
Published: November 2021

Background
The lateral transmalleolar approach (LTA) is a surgical approach for posterior malleolar fractures (PMFs), providing direct visualization of the articular surface of the posterior malleolus, though temporarily disrupting the syndesmosis. However, it is still unclear whether this fibrous joint can be effectively reconstructed afterward to prevent complications. We report the clinical results and computed tomography (CT) findings for articular and syndesmosis reduction status after surgery with LTA for PMF.
Methods
Sixteen patients who underwent PMF reduction with LTA and were followed up for at least 1 year were evaluated retrospectively. According to the AO/OTA classification, the fracture type was type 44B in 13 patients and 44C in three patients. The Haraguchi classifications of PMF were type 1 in six cases and type 2 in 10 cases. The American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS) score, post-surgical complications, and reduction status of PMF and syndesmosis on CT were investigated.
Results
The mean AOFAS score was 93.0 ± 5.2 points. Post-operative complications were observed in one case of superficial infection and one case of delayed fibular union. The articular step-off seen on CT improved significantly after surgery (5.9 ± 2.9 mm preoperatively vs. 0.6 ± 0.8 mm post-operatively). Syndesmosis malreduction was seen in three cases, including two high fibular fractures and one comminuted fibular fracture with osteoporosis.
Conclusions
The LTA provided favourable clinical results and effective reduction of intra-articular PMFs. However, surgeons should be aware of the possibility of syndesmosis malreduction in cases of high fibular fractures or comminuted fibular fractures.
Synthesis and Characterization of Non-Stoichiometric Li1.1Co0.3Fe2.1O4 Ferrite Nanoparticles For Humidity Applications
Authors: ElFarhatey Ebtesam Ateia , Ateia Mahmoud A. , Mosry M.M. , Singh Charanjeet , Arman M.M.
Published: November 2021

Humidity sensor plays a crucial role in determining the efficiency of materials and the precision of apparatuses. To measure and control humidity, a non-stoichiometric Li1.1Co0.3Fe2.1O4 mesopores sensor is synthesized by a modified citrate auto combustion technique. The XRD study confirms that prepared nanoparticles are cubic spinel structures having Fd3m space group. The crystallite size is approximate 36 nm. Thermal analyses measurements confirm that the samples become thermally stable starting from 600 °C. Additionally, the kinetic studies of the prepared samples are calculated via a pseudo-first-order kinetic model. The temperature dependence of AC conductivity is found to increase with increasing the temperature. These observations are explained in various models. The resistivity mechanism of humidity sensors is studied via Complex impedance spectroscopy (CIS). Its impedance data is fitting to a corresponding circuit, to achieve a simulation of the sample under study. This fitting is detected by the Nyquist plot (Cole-Cole). The obtained data confirms that the studied samples are very sensitive to humidity and can be commercially used as a humidity sensing element.
Economic Growth and Quality Adjusted Human Capital Equation: Moderating Role of Social Capabilities in Africa
Authors: Joseph Tonuchi Emmanuel , Obikaonu Pauline Chimuru
Published: November 2021

The role of human capital on economic growth across countries has over time garnered lots of discussion in economic literature. This is fundamental, given that the actual determinant of the difference in income per capita across countries or why some countries are growing faster than other countries has remained an unresolved issue. This study provides a different insight into the nexus between human capital and economic growth by accounting for the role of social capabilities in a panel framework. Specifically, the study covers 40 African countries between 1998-2019, where the General Method of Moment (GMM) was employed to estimate the model. Specifically, it was discovered that without improved legal institutions and better economic opportunities, human capital impact on the growth of income per capita across countries is insignificant though positive. The study concludes that the effectiveness of knowledge accumulation and adoption of technology in a country is hinged on the availability of an enhanced legal, social, and economic environment.
WITHDRAWN: Performance Analysis of Optimal Sized Hybrid Renewable Energy Grid-Connected Systems.
Authors: Prajapati Anjani Kumar , Srivast Sudhir Kumar
Published: November 2021

Hybrid solar energy-based power generation systems (PGS) are one of the exciting options for potential distributed networks. PV and wind grid linked PGSs are the most appropriate for its good output across various configurations. However, due to the system's complexity, special attention is required to achieve a successful engineering solution in the optimal balance between these two energy sources. This paper discusses optimum scale of PV and wind by following multiple optimization methods to various condition decision analysis (VCDA). The versatility of the VCDA algorithm was tested by taking into account several weighting parameter techniques for differing wind speeds and fluctuations in radiation levels, thus illustrating the advantages and limitations of the suggested optimum size approaches. The subsequent study may be called as a significant reference for decision makers, analysts and policymakers.
WITHDRAWN: A Novel Approach for Mitigating Power Quality Issues in a PV Integrated Microgrid System Using an Improved Jelly Fish Algorithm
Authors: Suman Swati , Chatterjee Debashis , Mohanty Rupali
Published: November 2021

A two-step methodology was used to address the power quality concerns for the PV integrated microgrid system. In the first step, partial shading was included to deal with the real-time issues. The Improved Jelly Fish Algorithm integrated Perturb and Obserb (IJFA-PO) has been proposed to track the Global Maximum Power Point (GMPP). In the second step, the main unit powered by a DC-AC converter is synchronised with the grid. To cope with the wide voltage variation, an auxiliary unit is connected to the main unit in the opposite phase. This study evaluates various switching approaches to determine the optimal solution for achieving the stated goals. It was found that the IJFA-based SHE in 120 օ conduction gives improved results. A novel series compensation technique has been employed to further eliminate harmonics before grid integration. The proposed IJFA has been used to determine the switching angles for the SHEPWM converter. The objective function and novel series compensation work together to determine the harmonics that should be decreased and kept to a minimum. Three switching angles' performance was equivalent to that of nine switching angles. As a result, higher-order harmonics can be minimised with fewer switches, and switching losses can be lowered without compromising efficiency. The THD of the proposed system was 1.32 percent, which is very much within the tolerable limit of IEEE 1547, IEC, and CIGRE WG 36-05 standards. In terms of efficiency, metaheuristics, and convergence, the proposed system outperformed the existing ones. The model was developed in MATLAB/Simulink 2016b. To verify the simulation results, an experimental prototype of grid synchronised PV capacity of 260W was tested under various loading conditions. The present model is reliable and features a simple controller that provides more convenient and adequate performance for practical reasons.
A Dynamic K-means Based Clustering Algorithm Using Fuzzy Logic for CH Selection and Machine Learning Based Data Transmission
Authors: Choudhary Anupam , Badholia Abhishek , Sharma Anurag , Patel Brijesh , Jain Sapna
Published: November 2021

Clustering is effective method to increase network lifetime, energy efficiency, and connectivity of Sensor nodes in wireless sensor network. An energy efficient clustering algorithm has been proposed in this paper. Sensor nodes are clustered using K-means algorithm which dynamically forms number of clusters in accordance with number of alive nodes. Selection of suitable CH is done by fuzzy inference system by choosing three fuzzy input variable such as residual energy of Sensor node, its distance from cluster center and base station. Amount of data transmitted by member nodes to CH is reduced by machine learning that classify similar data at regular interval. The simulation results show that proposed algorithm outperforms other cluster based algorithms in terms of data received by base station, number of alive node per round, time of first node, middle node and last node to die for various density of sensor nodes and scalable conditions.
Long Term Surgical Oncological and Functional Outcome of Large Petroclival and Cerebellopontine Angle Epidermoid Cysts: A Multicenter Study.
Authors: Sellier Aurore , Troude Lucas , Baumgarten Clément , Caudron Yohan , Bretonnier Maxime , Gallet Clémentine , Boissonneau Sébastien , Cungi Pierre-Julien , Morandi Xavier , Dufour Henry , Fournier Henri-Dominique , Gay Emmanuel , Kalamarides Michel , Roche Pierre-Hugues
Published: November 2021

Objective: To assess the long-term surgical results on cranial nerve (CN) function and tumor control in patients harboring cerebellopontine angle (CPA) and petroclival area (PCA) epidermoid cysts (EC).Methods: This is a retrospective cohort study about 56 consecutive patients operated on for a CPA or PCA EC between January 2001 and July 2019 in six participating French cranial base referral centers.Results: Sixteen patients (29%) presented a PCA EC, and 40 a CPA EC (71%). The median clinical and radiological follow-up was 46 months (range 0-409). Preoperative CN disorders were present in 84% of patients (n=47), 72% of them experienced CN deficits improvement at last follow-up consultation (n=34) : 60% of cochlear and vestibular deficits (n=9/15 in both groups), 67% of trigeminal neuralgia (n=10/15), 53% of trigeminal hypoesthesia (n=8/15), 44% of lower cranial nerve disorders (n=4/9), 38% of facial nerve deficits (n=5/8), and 43% of oculomotor deficits (n=3/7) improved or were cured after surgery. New postoperative CN deficits occurred in 48% of patients (n=27). Most of them resolved at last follow-up, except for cochlear deficits which improved in only 14% of cases (n = 1/7). Twenty-six patients (46 %) showed evidence of tumor progression after a median duration of 63 months (range 7-210). Extent of resection, tumor location and tumor size were not associated with the occurrence of new postoperative CN deficit nor tumor progression. Conclusion: A functional nerve-sparing resection of posterior fossa EC is an effective strategy to optimize the results on preexisting CN deficits and reduces the risk of permanent de novo deficits.
A Rare Case of Iliopsoas Abscess in a Term Neonate – Case Report and Brief Review of Literature
Authors: Peddu Sai Praveen , Nanda Debasish , Pradhan Antaryami , Kumar TV Ram
Published: November 2021

Iliopsoas abscesses are rare in neonates. Clinical presentation of neonates with iliopsoas abscess often mimic other common neonatal illness. Typical clinical features as described in adults may not be observed in neonates. Such abscesses cause a diagnostic dilemma for the clinician, often resulting in a delay in clinical diagnosis and institution of specific treatment. We report a case of a 10-day old term male neonate from community who presented with high grade fever, abdominal distension, left lower limb swelling with limitation of movement and diagnosed to have left sided iliopsoas abscess on ultrasonography. The neonate undergone and extraperitoneal surgical drainage of the abscess along with a course systemic antimicrobial agent. The case is of clinical importance because it describes the presence of a localized abscess in an uncommon location and Methicillin resistant staphylococcus being the causative organism, which represents a rare and potentially life-threatening infection in neonates.
Organic Matter And Anaerobic Cellulolytic Activity In Sediments of Ashtamudi Estuary, Kerala, India
Authors: Arya Dennison Bindhulekha , Vincent Salom Gnana Thanga , Reshma J.K , Salahudeen Junaid Hassan
Published: November 2021

Estuarine sediments are best suited for bioprospecting cellulose degrading microorganisms because of continuous input of cellulosic carbon from rivers and terrestrial runoff, and such sediments act as a substrate for decomposition by microbes. Sediment samples were collected from thirteen stations of Ashtamudi estuary, a tropical Ramsar site during April 2016 and January 2017 and analysed for environmental variables such as temperature, pH, electrical conductivity, oxidation- reduction potential, sulphate, total organic carbon (Corg), carbohydrate, protein, lipid and labile organic matter. Microcosm experiments were conducted in the sediment samples to compare native and substrate-induced cellulase enzyme activities in mesophilic and thermophilic conditions added with crystalline cellulose and cellobiose as substrates. Abundance of cellulolytic anaerobes in the roll tubes was higher with cellobiose than crystalline cellulose. Substrate induced enzyme activity was more than native enzyme activity [0.0012±0.0001- 0.004±0.002 (April 2016) and 0.004±0.001- 0.161±0.002 mg glucose h-1 (January 2017)] in the sediment samples and cellulolytic activity was more pronounced in thermophilic conditions during April 2016. Redundancy analysis indicated that salinity was the highest determining factor for explaining variations among bacterial abundance and activity during April 2016 and sediment lipid content during January 2017. The study reveals that estuarine sediments can act as a potential source of thermophilic cellulase enzyme producing bacteria, which needs to be further explored owing to their vast industrial applications.
The Cyclical Sine Model Explanation for Climate Change
Authors: Nierode Dale Erwin
Published: November 2021

Climate Change due to excessive buildup of greenhouse gasses in the atmosphere from hydrocarbon combustion is one explanation (NASA greenhouse effect) for the Earth’s temperature increase since 1850. If this is true, then eliminating fossil fuel use is the only way to preserve our planet. However, there is another explanation for Global Warming/Climate Change that leads to the opposite conclusion – hydrocarbon energy will be needed well into the future to cope with future, excessively hot and cold temperature cycles. This paper will show that the Global Warming/Climate Change underway on Earth today is a totally natural occurrence with solid scientific and historical support. The Earth is currently in the upswing part of its normal temperature cycle. Very warm (Medieval Warming) and very cold (Little Ice Age) cycles have been historically documented on Earth for at least the last 3,000 years. This cyclicity has a repeated period of about every 1,500 years (Singer 2008). This explanation for the Earth’s temperature increases since 1850 is captured in a mathematical model called the Cyclical Sine Model. This model fits past climate cycles, measured temperatures since 1850, and correlates closely with the cyclicity of Bond Atlantic Drift Ice Cycles (Bond 1997), the Atlantic Multidecadal Oscillation (NASA AMO), and the Pacific Decadal Oscillation (NASA PDO). This model also quantitively explains the time span 1945-1975 when an impending ice age was feared (Time Magazine 1974). The Cyclical Sine Model is the best explanation for the Earth’s recent temperature increases.
Postpartum Haemorrhage in Anaemic Women: Assessing Outcome Measures for Clinical Trials
Authors: Brenner Amy Charlotte , Roberts Ian , Balogun Eni , Bello Folasade Adenike , Chaudhri Rizwana , Fleming Charlotte , Javaid Kiran , Kayani Aasia , Lubeya Mwansa Ketty , Mansukhani Raoul , Olayemi Oladapo , Prowse Danielle , Vwalika Bellington , Shakur-Still Haleema
Published: November 2021

Background: Post-partum haemorrhage (PPH) is a leading cause of maternal mortality worldwide. Maternal anaemia greatly increases the risk of PPH and over a third of all pregnant women are anaemic. Because anaemia reduces the oxygen-carrying capacity of the blood, anaemic women cannot tolerate the same volume of blood loss as healthy women. Yet the same blood loss threshold is used to define PPH in all women. The lack of an established PPH definition in anaemic women means the most appropriate outcome measures for use in clinical trials are open to question. We used data from the WOMAN-2 trial to examine different definitions of PPH in anaemic women and consider their appropriateness as clinical trial outcome measures. Main body: The WOMAN-2 trial is assessing tranexamic acid (TXA) for PPH prevention in women with moderate or severe anaemia at baseline. To obtain an accurate, precise estimate of the treatment effect, outcome measures should be highly specific and reasonably sensitive. Some outcome misclassification is inevitable. Low sensitivity reduces precision, but low specificity biases the effect estimate towards the null. Outcomes should also be related to how patients feel, function, or survive. The primary outcome in the WOMAN-2 trial, a ‘clinical diagnosis of PPH’, is defined as estimated blood loss >500 ml or any blood loss within 24 hours sufficient to compromise haemodynamic stability. To explore the utility of several PPH outcome measures, we analysed blinded data from 4,521 participants. For each outcome, we assessed its: 1) frequency, 2) specificity for significant bleeding defined as shock index ≥1.0, and 3) association with fatigue (modified fatigue symptom inventory [MFSI]), physical endurance (six-minute walk test) and breathlessness. A clinical diagnosis of PPH was sufficiently frequent (7%), highly specific for clinical signs of early shock (95% specificity for shock index ≥1) and associated with worse maternal functioning after childbirth.Conclusion: Outcome measures in clinical trials of interventions for PPH prevention should facilitate valid and precise estimation of the treatment effect and be important to women. A clinical diagnosis of PPH appears to meet these criteria, making it an appropriate primary outcome for the WOMAN-2 trial.Clinical trial registration: ClinicalTrials.gov NCT03475342, registered on 23 March 2018; ISRCTN62396133, registered on 7 December 2017; Pan African Clinical Trial Registry PACTR201909735842379, registered on 18 September 2019.
Research On Medical Insurance Policies Against Serious Illness Among Urban And Rural Residents In Shanghai Based On Micro-Simulation
Authors: Li Yang , Duan Guangfeng , Xiong Linping
Published: November 2021

Background: Urban and rural residents’ basic medical insurance (URRBMI) is an institutional arrangement for rural residents and unemployed urban residents in China. The serious illness medical insurance system (SIMIS) was established to provide additional medical cover. There are two ways in which medical expenses are covered. One is based on large expenses and provides proportional compensation for the individual’s own expenses after the URRBMI payment; the other is to pay for the treatment of some serious diseases after the URRBMI payment. At present, the SIMIS payment method in China is based on large expenses, and only a few areas, such as Shanghai, pay according to the treatment of serious diseases. This study aims to simulate and analyse the effect of the two payment methods on SIMIS in Shanghai. Methods: We developed a micro-simulation model to predict the number and characteristics of SIMIS participants among urban and rural residents in Shanghai and to simulate the process of medical treatment, medical consumption, and medical insurance payments for each insured person from 2020 to 2025. We then summarised and analysed the payment compensation effect, and compared it with Shanghai’s current policies.Results: Under the current financing standard, the payment of SIMIS according to high expenses is not sustainable and the compensation is insufficient and cannot effectively prevent or alleviate poverty.Conclusions: The policy of designing SIMIS according to national guidelines does not meet the development needs of Shanghai. Shanghai should take the current policy of paying compensation according to the treatment of serious illness as the policy basis, consider the security needs of patients with large medical expenses outside the scope of protection, and adjust policies appropriately to prevent poverty caused by illness.
Potentially Toxic Elemental Contamination in Wainivesi River, Fiji Impacted by Gold-mining Activities using Chemometric Tools and SOM Analysis
Authors: Kumar Satendra , I Abu Reza Md. Towfiqul , Hasanuzzaman Md. , Salam Roquia , Islam Md. Saiful , Khan Rahat , Rahman M. Safiur , Pal Subodh Chandra , Ali Mir Mohammad , Idris Abubakr M. , Gustave Williamson , Elbeltagi Ahmed
Published: November 2021

Potentially toxic elements (PTEs) contamination in Wainivesi River, Fiji triggered by gold-mining activities is a major public health concern deserving attention. However, chemometric approaches and pattern recognition of PTEs in surface water and sediment are yet hardly studied in Pacific Island countries like Fijin urban River. In our study, twenty-four sediment and eight water sampling sites from the Wainivesi River, Fiji were explored to evaluate the spatial pattern, eco-environmental pollution, and source apportionment of PTEs. This analysis was done using an integrated approach of self-organizing map (SOM), principle component analysis (PCA), hierarchical cluster analysis (HCA), and indexical approaches. The PTEs average concentration is decreasing order of Fe > Pb > Zn > Ni > Cr > Cu > Mn > Co > Cd for water and Fe > Zn > Pb > Mn > Cr > Ni > Cu > Co > Cd for sediment, respectively. Outcomes of eco-environmental indices including contamination and enrichment factors, and geo-accumulation index differed spatially indicated that majority of the sediment sites were highly polluted by Zn, Cd, and Ni. Cd and Ni contents can cause both ecological and human health risks. According to PCA, two sources such as point and geogenic sources for sediment and also two sources including weathering of rock-water and anthropogenic sources of PTEs for water were identified in the study area. The SOM analysis identified three spatial patterns e.g., Cr-Co-Zn-Mn, Fe-Cd and Ni-Pb-Cu in water and Zn-Cd-Cu-Mn, Cr-Ni and Fe, Co-Pb in sediment. Spatial distribution of entropy water quality index values depicted that northern and northwestern areas possess ‘poor’ to ‘extremely-poor’ quality water. The entropy weights indicated Zn, Cd and Cu as the major pollutants in deteriorating the water quality. Our finding provides a baseline database with eco-environmental and health risk measures for the Wainivesi river contamination.
Tim-3ScFv-Transforming Lactobacillus Inhibits Transplanted Tumour of Renal Cell Carcinoma
Authors: Chen Zerong , Zhang Haibo , Hui Jialiang , Jiang Yaodong , Huang Zehai , Chen Zhuangfei , Zeng Weisen
Published: November 2021

Background

T cell immunoglobulin-3(Tim-3) is an immune checkpoint molecule; Tim-3 antibody is suitable for treating malignant renal tumours. However, Tim-3 antibody drugs are expensive, which limits their application. To overcome the disadvantages of expensive immunotherapeutic drugs, Lactococcus lactis was used as the host bacteria to express Tim-3 single-chain antibody in the intestine, and its promotion of the mouse immune system and inhibitory effects on the transplanted tumour of kidney cancer in mice were tested.
Methods

Molecular cloning technology was used to construct plasmids pLAN-CTB-Tim3scFv and pLAN-Tim3scFv, which were transformed into Lactococcus lactis. The expression of the transformed bacteria was analysed using western blotting, and the immune activity of secreted proteins of the transformed bacteria was detected using ELISA in vitro. A subcutaneous transplanted tumour model of renal adenocarcinoma was constructed in RAG mice, and the promoting effect of transforming bacteria on the activation of mouse spleen lymphocytes, and its inhibitory effect on transplanted tumours in mice was analysed.
Results

(1) Transformed Lactococcus lactis NZ -CTB-Tim3scFv and NZ -Tim3scFv, which secrete CTB-Tim3scFv and Tim3scFv single-chain antibodies, were successfully constructed. (2) CTB-Tim3scFv secreted by NZ-CTB-Tim3scFv transformed bacteria showed immunological activity. (3) Compared with the NZ-Tim3scFv and NZ-Vector groups, the characteristics of the subgroups of splenic lymphocytes in the NZ-CTB-Tim3scFv group had a higher proportion of CD3+CD4+, CD3+CD8a+, and CD3+CD69+ cells. Ki67 and CD31 expression in the NZ-CTB-Tim3scFv group was significantly reduced. The tumour volume of the NZ-CTB-Tim3scFv group increased the least, and was statistically different from that of the other two groups.
Conclusions

The Tim-3 single-chain antibody gene was successfully constructed and transformed in Lactococcus lactis. After feeding mice NZ-CTB-Tim3scFv transforming Lactobacillus, the CTB-Tim3scFv secreted by the transforming Lactobacillus promoted the proliferation and activation of spleen lymphocytes and inhibited volume growth, cell proliferation, and angiogenesis of the tumour in mice. In summary, apply transgenic lactobacillus secreting CTB-Tim-3scFv, to perform its role in anti-tumor immunotherapy through oral approach, is low cost and convenient. It is expected to become a new way of immunotherapy for renal cell carcinoma.
PPARG, GNG12, and CD19 are Potential Independent Predictors of Central Nerve Recurrence in Childhood Acute Lymphoblastic Leukemia
Authors: Zhang Shan , Tu Yansong , Wu Qianmiao , Chen Huijun , Tu Huaijun , Li Jian
Published: November 2021

Objective: To identify biomarkers that can predict the recurrence of the central nervous system (CNS) in children with acute lymphoblastic leukemia (ALL), and establish a prediction model. Materials and Methods: The transcriptome and clinical data collected by the Children's Oncology Group (COG) collaboration group in the Phase II study (use for test group) and Phase I study (use for validation group) of ALL in children were downloaded from the TARGET database. Transcriptome data were analyzed by bioinformatics method to identify core (hub) genes and establish a risk assessment model. Univariate Cox analysis was performed on each clinical data, and multivariate Cox regression analysis was performed on the obtained results and risk score. The children ALL phase I samples collected by the COG collaboration group in the TARGET database were used for verification. Results: A total of 1230 differentially expressed genes were screened out between the CNS relapsed and non-relapsed groups. Univariate multivariate Cox analysis of 10 hub genes identified showed that PPARG (HR=0.78, 95%CI=0.67-0.91, p=0.007), CD19 (HR=1.15, 95%CI=1.05-1.26, p=0.003) and GNG12 (HR=1.25, 95%CI=1.04-1.51, p=0.017) had statistical differences. The risk score was statistically significant in univariate (HR=3.06, 95%CI=1.30-7.19, p=0.011) and multivariate (HR=1.81, 95%CI=1.16-2.32, p=0.046) Cox regression analysis. The survival analysis results of the high and low-risk groups were different when the validation group was substituted into the model (p=0.018). In addition, the CNS involvement grading status at first diagnosis CNS3 vs. CNS1 (HR=5.74, 95%CI=2.01-16.4, p=0.001), T cell vs B cell (HR=1.63, 95% CI=1.06-2.49, p=0.026) were also statistically significant. Conclusions: PPARG, GNG12, and CD19 may be predictors of CNS relapse in childhood ALL.
Comparative study on efficacy and safety of ultrasound guided transoral and transcutaneous core needle biopsy in patients with oral masses
Authors: Wei Ting , Lu Man , Li Juan , Hu Ziyue , Li Tingting , Cheng Xueqing , Wang Lu , Pu Wei
Published: November 2021

Background
Ultrasound (US) guided transoral biopsy is a novel and safe procedure for obtaining tissue in patients with oral masses. However, this procedure is less commonly used in comparison to US guided transcutaneous biopsy. The aim of this study is to compare the efficacy and safety of US-guided transoral and transcutaneous core needle biopsy (CNB) in patients with oral masses.
Methods
From November 2019 to March 2021, consecutive patients with oral masses were randomly assigned to undergo US-guided transoral CNB (transoral group) and US-guided transcutaneous CNB from a submental approach (transcutaneous group). During the operation, procedure time, intra‑operative blood loss volume, diagnostic performance, rate of complications and pain level were recorded and compared.
Results
There were 112 patients (62 in the transoral group and 50 in the transcutaneous group) evaluated in this study. The postprocedural complication rate of the transcutaneous group was significantly higher than the transoral group (24% vs 0%, P=0.000). There was no significant difference in accuracy (95.2% vs 88%, P = 0.30), biopsy time (76±12 seconds vs 80±13 seconds, p=0.09), blood losses (2.6±0.5 ml vs 2.7±0.4 ml, p=0.17) and visual analogue score (p=0.327 and p =0.444 before and after the sampling procedure) between the two groups.
Conclusion
US-guided transoral CNB results in high rates of technical success and lower rates of postprocedural complications.
Identifying Dihydropyrimidine Dehydrogenase as a Novel Regulator of Hepatic Steatosis
Authors: Sullivan Kelly E. , Kumar Sheetal , Liu Xin , Zhang Ye , Koning Emily , Li Yanfei , Yuan Jing , Fan Fan
Published: November 2021

Pyrimidine catabolism is implicated in hepatic steatosis. Dihydropyrimidine Dehydrogenase (DPYD) is an enzyme responsible for uracil and thymine catabolism, and DPYD human genetic variability affects clinically observed toxicity following 5-Fluorouracil (5-FU) administration. In an in vitro model of diet-induced steatosis, the pharmacologic inhibition of DPYD resulted in protection from lipid accumulation. Additionally, a gain-of-function mutation of DPYD, created through clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR-Cas9) engineering, led to an increased lipid burden, which was associated with altered mitochondrial functionality in a hepatocarcionma cell line. The studies presented herein describe a novel role for DPYD in hepatocyte metabolic regulation as a modulator of hepatic steatosis.
Financial Inclusion and Its Influence on Economic-environmental Performance: Demand and Supply Perspectives
Authors: Liu Dong , Zhang Yuying , Hafeez Muhammad , ullah Sana
Published: November 2021

In this study, we want to test the impact of financial inclusion on the economic growth and the environmental quality of OBOR economies. We have selected four different proxies of financial inclusion, two from the perspective of the supply side and two from the perspective of the demand side. For empirical analysis, we have applied 2SLS and GMM methods. In the economic growth model, among the variables of financial inclusion, only the variable of ATMS is positively significant when we apply the 2SLS approach and all others are insignificant, however, when we apply the GMM approach two variables i.e. ATMS and branches are positively significant implying that supply-side financial inclusion is vital for economic growth in OBOR countries. On the other side, the variables of financial inclusion, whether supply-side or demand-side, exerted a positive impact on the CO2 emissions irrespective of the estimation techniques i.e. 2SLS and GMM. These findings imply that financial inclusion, in general, causes CO2 emissions to rise.
Potentially Preventable Hospital Readmissions After Patients’ First Stroke—A National Population-Based Study In Taiwan
Authors: Chiou Ling-Jan , Lang Hui-Chu
Published: November 2021

Readmission is an important indicator of the quality of care. The purpose of this study was to explore the probabilities and predictors of 30-day and 1-year potentially preventable hospital readmission (PPR) after a patient’s first stroke. We used claims data from the National Health Insurance (NHI) from 2010 to 2018. Multinomial logistic regression was used to assess the predictors of 30-day and 1-year PPR. A total of 41,921 discharged stroke patients was identified. We found that hospital readmission rates were 15.48% within 30-days and 47.25% within 1-year. The PPR and non-PPR were 9.84% (4,123) and 5.65% (2,367) within 30-days, and 30.65% (12,849) and 16.60% (6,959) within 1-year, respectively. The factors of older patients, type of stroke, shorter length of stay, higher Charlson Comorbidity Index (CCI), higher stroke severity index (SSI), hospital level, hospital ownership, and urbanization level were associated significantly with the 30-day PPR. In addition, the factors of gender, hospitalization year, and monthly income were associated significantly with 1-year PPR. The results showed that better discharge planning and post-discharge follow-up programs could reduce PPR substantially. Also, implementing a post-acute care program for stroke patients has helped reduce the long-term PPR in Taiwan.
TWIICE One powered exoskeleton: Effect of design improvements on usability in daily-life as measured by Cybathlon race performance
Authors: Vouga Tristan , Fasola Jemina , Baud Romain , Manzoori Ali Reza , Pache Julien , Bouri Mohamed
Published: November 2021

Background

Spinal cord injury leading to paraplegia affects the mobility and physiological well-being of nearly one in a thousand people. Powered exoskeletons can temporarily restore the ability to walk. Their relevance in daily life is still limited because of low performance beyond even ground. Cybathlon is an international competition promoting improvements in assistive technology. In this article we present the latest design and results of testing of TWIICE One 2018, one of the competing devices in the 2020 race.
Methods

A person with a motor-complete spinal cord injury at thoracic level T10 participated as race pilot. Training ahead of the race took place over one week at a rate of 2-5 hours per week. Time to perform each of the 7 tasks of the competition was recorded together with the number of repetitions. Performance is compared over training time and against 2016 race results.
Results

Progression was observed in all tasks and accounted for by both user training and technology improvements. Final competition rank was second out of 7 participating teams, with a record time of 4'40" min. This represents an average of 40 % improvement with respect to comparable obstacles of the 2016 race, explaining the two ranks of improvement since then.
Conclusion

These results help understand which features had a positive impact on real life performance of the device. Understanding how design affects performance is a key information to create devices that really improve the life of people living with paraplegia.
Three-dimensional Printed Polylactic Acid and Hydroxyapatite Composite Scaffold with Urine-derived Stem Cells Treatment for Bone Defects
Authors: Zhang Xiang , Chen Jialei , Wang Hongren , Duan Xin , Gao Feng
Published: November 2021

BACKGROUND: Bone defects still pose various challenges in osteology. As one of the treatment options for bone defects, bone tissue engineering requires biomaterials with good biocompatibility and seed cells with good differentiation capacity. This study aimed to fabricate a 3D-printed polylactic acid and hydroxyapatite (PLA/HA) composite scaffold with urine-derived stem cells (USCs) to study its therapeutic effect in a model of skull defect in rats.METHODS: USCs, isolated and extracted from the urine of healthy adult males, were inoculated onto a 3D-printed PLA/HA composite scaffold and a PLA scaffold. Skull defect model rats were randomly divided into three groups (control, PLA, and PLA/HA). Twelve weeks after implanting scaffolds containing USCs into rats with a skull defect, the therapeutic efficacy was evaluated by real-time PCR, micro-CT, histology, and immunohistochemistry.RESULTS: The 3D-printed PLA/HA composite scaffold had good mechanical properties and porosity. The adhesion and proliferation of USCs on scaffolds also demonstrated excellent biocompatibility. PLA and PLA/HA containing USCs promoted bone regeneration in the defect area, supported by the general observation and CT images at 12 weeks after treatment, with coverage of 74.6%±1.9% and 96.7%±1.6%, respectively. Immunohistochemical staining showed a progressive process of new bone formation on PLA/HA scaffolds containing USCs at the defect site compared to that in PLA and control groups.CONCLUSION: The 3D-printed PLA/HA composite scaffold with USCs was successfully applied to the skull defect in rats. Under the linkage of the scaffold, the proliferation, differentiation, and osteogenesis expression of USCs were promoted near the bone defect area. These findings demonstrated broad application prospects of PLA/HA scaffolds with USCs in bone tissue engineering.