bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Tramadol with Bupivacaine Versus Bupivacaine Alone on Postoperative Analgesia at Wolaita Sodo, Southern Ethiopia: Observational Cohort Study
Authors: G/medhin Tsegaye Demeke , Obsa Mohammed Suleiman , Andebirku Andualem Asefa , Gemechu Ashebir Debalike , Haile Kirubel Eshetu
Published: June 2021

Background: Postoperative pain can cause immediate and extended consequences of poor outcome and result in extended hospitalization. It also progresses to chronic pain, if not intervening early. Wound site infiltration with a mixture of tramadol and bupivacaine is inexpensive, easy, and useful means of providing desirable analgesia for postoperative pain relief. The purpose of the study was to compare the analgesic effectiveness of bupivacaine with the tramadol combination and bupivacaine alone as part of postoperative pain management.Method: A prospective cohort study was employed on 120 patients who underwent elective lower abdominal surgery under general or spinal anesthesia with a systematic random sampling technique. Pain severity was measured by using a numerical rating scale, and the employment of additional analgesics was recorded for 24 hours between the two groups. The Mann-Whitney test and chi-square test were used to compare the median pain score and total analgesia consumption. Kaplan-Meier survival analysis was used to compare the time to first analgesic request between the two groups. Statistical significance was stated at a p value < 0.05 with a power of 95%.Result: Postoperatively, the median (interquartile range) of pain severity score was 1.0 (0-5) in the BT group compared with 5 (3-6) in the BA group. And, time to first analgesic request with the BT group, was 18 hours, 95% CI: (14.53- 21.47), had longer time compared to patients in the BA group was 6 hours, 95% CI:(4.48 - 7.71).Conclusion and Recommendation: Local wound infiltration with a mixture of Bupivacaine and Tramadol decreases the postoperative pain score, total analgesia consumption and has prolonged time to first analgesia request. Therefore, we recommend using a mixture of 0.25% bupivacaine with tramadol is effective for postoperative analgesia.
Constitutive Silencing of LRRK2 Kinase Activity Leads to Early Glucocerebrosidase Deregulation and Late Impairment of Autophagy in vivo
Authors: Albanese Federica , Mercatelli Daniela , Finetti Luca , Lamonaca Giulia , Pizzi Sara , Shimshek Derya , Bernacchia Giovanni , Morari Michele
Published: June 2021

Background: Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with familiar and sporadic Parkinson’s disease. LRRK2 modulates the autophagy-lysosome pathway (ALP), a clearance process subserving the quality control of cellular proteins and organelles. Since dysfunctional ALP might lead to α-synuclein accumulation and, hence, Parkinson’s disease, LRRK2 kinase modulation of ALP, its age-dependence and relation with pSer129 a-synuclein inclusions in striatal and nigral neurons were investigated in vivo. Methods: Striatal ALP markers were analyzed by Western blotting in 3, 12 and 20-month-old LRRK2 G2019S knock-in mice (bearing enhanced kinase activity), LRRK2 knock-out mice, LRRK2 D1994S knock-in (kinase-dead) mice and wild-type controls. The lysosomotropic agent chloroquine was used to investigate the autophagic flux in vivo. Quantitative Real-time PCR was used to quantify the transcript levels of key ALP genes. The activity of the lysosomal enzyme glucocerebrosidase was measured using enzymatic assay. Immunohistochemistry was used to co-localize LC3B puncta with pSer129 a-synuclein inclusion in striatal MAP-positive and nigral TH-positive neurons. Results: No genotype differences in macroautophagy and chaperone-mediated autophagy markers were observed at 3 months. Conversely, increase of LC3-I, p62, LAMP2 and GAPDH levels, decrease of p-mTOR levels and downregulation of mTOR and TFEB expression was observed in 12-month-old kinase-dead mice. The LC3-II/LC3-I ratio was reduced following administration of chloroquine, suggesting a defective autophagic flux. G2019S knock-in mice showed LAMP2 accumulation and downregulation of ALP key genes MAP1LC3B, LAMP2, mTOR, TFEB and GBA1. Subacute administration of the LRRK2 kinase inhibitor MLi-2 in wild-type and G2019S knock-in mice did not replicate the pattern of kinase-dead mice. Lysosomal glucocerebrosidase activity was increased in 3 and 12-month-old knock-out and kinase-dead mice, and GBA1 expression reduced in 12-month-old G2019S knock-in mice. Immunofluorescence revealed a dissociation between LC3B puncta accumulation and pSer129 a-synuclein inclusions in striatal neurons of kinase-dead and G2019S knock-in mice. Conclusions: We conclude that constitutive LRRK2 kinase silencing results in early deregulation of GCase activity followed by late impairment of macroautophagy and chaperone-mediated autophagy. In G2019S knock-in mice, pSer129 a-synuclein inclusions observed under basal conditions appear unrelated to autophagy impairment.
Multiple Mutations of CYP2C19, PON1 and ABCB1 Influence Platelet Response, Bleeding and Thrombosis Risk to Clopidogrel after Percutaneous Coronary Intervention: A Retrospective Study
Authors: Jin Hui , Song Jinfei , Shen Xiaoying , Liang Qing , Sun Guangchun , Yu Yan
Published: June 2021

Background:Different combinations of multiple mutations of CYP2C19, PON1and ABCB1 for the efficiency and safety of Clopidogrel in patients undergoing percutaneous coronary intervention (PCI) remain unclear.Methods: 263 Chinese Han patients receiving 75mg Clopidogrel and 100mg Aspirin every day for 12 months after PCI were enrolled in this study. ADP-induced platelet aggregation rates, thrombosis and bleeding risk are used to compare the Clopidogrel response among the combined genetic mutation. Results: Our study demonstrated that multiple genetic mutations are very common in patients receiving Clopidogrel and Aspirin after PCI.Patients who have high ADP-induced platelet aggregation rate with more mutations of CYP2C19, PON1 and ABCB1. Patients with full mutations of CYP2C19, PON1 and ABCB1 have highest risk of thrombosis and lowest risk of bleeding in patients receiving clopidogrel and aspirin with one-year follow-up duration.Conclusions:We summarized multiple genetic polymorphism influences platelet reactivity, bleeding and thrombosis risk to Clopidogrel after percutaneous coronary intervention.
Comparsion of Mobile-bearing UKA and Posterior Cruciate Ligament Retaining TKA for Patients with Unicompartmental Knee Osteoarthritis:a Retrospective Cohort Study
Authors: Wu Dan , Li Yang , Ruan Mingxuan , Ma GuangWen , Huang Fei
Published: June 2021

Introduction: Many studies have compared unicompartmental knee arthroplasty (UKA) with total knee arthroplasty (TKA) for knee osteoarthritis suggesting that both procedures had good clinical outcomes. However, there have been fewer studies comparing the mobile-bearing UKA (MB-UKA) and posterior cruciate ligament retaining TKA (CR-TKA) for patients with unicompartmental knee osteoarthritis. Thus, we explored the differences in outcomes and complications between the two cohorts.Methods: In this retrospective study, 41 patients who underwent MB-UKA and 40 who underwent CR-TKA in our institution were included. All patients were suffered from unicompartmental knee osteoarthritis. Patient demographics, preoperative and latest postoperative range of movement (ROM), Knee Society (KS) scores, and Forgotten Joint Score (FJS) were compared between the two cohorts. Additionally, complications, revisions, and 5-years survivorship were also analyzed.Results: The results showed MB-UKA patients had similar preoperative ROM and Knee Society pain (KSP), functional (KSF), and clinical (KSC) scores with CR-TKA patients (p = 0.104, p = 0.755, p = 0.32, p = 0.928, respectively). The mean follow-up for MB-UKA and CR-TKA groups was 3.4 and 3.7 years, respectively. Two MB-UKA and one CR-TKA patient required revision surgery. The latest postoperative KSF scores, ROM, FJS, and change in KSC scores and ROM were higher (p < 0.05) after MB-UKA, but the latest postoperative KSP, KSC, and change in KSF scores were equivalent between the two cohorts. There were no differences in complication, revision rates, and 5-year survivorship estimates.Conclusions: MB-UKA patients showed better functional outcomes and FJS, and higher ROM with similar survivorship compared with CR-TKA patients. MB-UKA should be considered as a primary treatment option for patients with unicompartmental knee osteoarthritis.Trial registration: researchregistry5032. Registered 23 July 2019, retrospectively registered
Epicardial Adipose Tissue and Postoperative Atrial Fibrillation
Authors: Laura Petraglia , Maddalena Conte , Giuseppe Comentale , Serena Cabaro , Pasquale Campana , Teresa Cante , Gerardo Gerundo , Carmela Russo , Ilaria Amaranto , Dario Bruzzese , Pietro Formisano , Emanuele Pilato , Dario Leosco , Valentina Parisi
Published: June 2021

Background. Atrial fibrillation (AF) often occurs after cardiac surgery and is associated to increased risk of stroke and mortality. Several evidence support the important role of inflammation in the pathogenesis of postoperative atrial fibrillation (POAF). It is known that an increased volume and a pro-inflammatory phenotype of epicardial adipose tissue (EAT) are both associated with AF onset in non surgical context. In the present study, we aim to evaluate whether also POAF occurrence may be triggered by an exalted production of inflammatory mediators from EAT.Methods. The study population was composed of 105 patients, with no history of paroxysmal or permanent AF, undergoing elective cardiac surgery. After clinical evaluation, all patients performed an echocardiographic study including the measurement of EAT thickness. Serum samples and EAT biopsies were collected before surgery. Levels of 10 inflammatory cytokines were measured in serum and EAT conditioned media. After surgery, cardiac rhythm was monitored for 7 days.Results. Forty-four patients (41.3%) developed POAF. As regard to cardiovascular therapy, only statin use was significantly lower in POAF patients (65.1% vs. 84.7%; p-0.032). Levels of Monocyte Chemoattractant Protein-1 (MCP-1), in both serum and EAT, were significantly higher in POAF patients (130.1 pg/ml vs. 68.7 pg/ml; p = < 0.001; 322.4 pg/ml vs. 153.4 pg/ml; p = 0.028 respectively). EAT levels of IL-6 were significantly increased in POAF patients compared to those in sinus rhythm (126.3 pg/ml vs. 23 pg/ml; p = < 0.005).ConclusionHigher EAT levels of IL6 and MCP1 are significantly associated with the occurrence of POAF. Statin therapy seems to play a role in preventing POAF. These results might pave the way for a targeted use of these drugs in the perioperative period.
Low Transmission Rates of Equine Infectious Anemia Virus (EIAV) in Foals Born To Seropositive Feral Mares Inhabiting the Amazon Delta Region Despite Climatic Conditions Supporting High Insect Vector Populations
Authors: Resende Cláudia Fideles , Santos Alison Miranda , Cook Richard Frank , Victor Raphael Mattoso , Câmara Rebeca Jéssica Falcão , Gonçalves Gilberto Pereira , Lima Juliana Gonçalves , Silva André Guimarães Maciel e , Leite Romulo Cerqueira , Reis Jenner Karlisson Pimenta
Published: June 2021

Background

Marajó Island within in the Amazon River Delta supports numerous bands of feral equids including the genetically distinct Marajoara horses. Roughly 40% of the equids on the island are infected with the Equine infectious anemia virus (EIAV). In the absence of iatrogenic transmission, spread of this lentivirus is mediated mainly by hematophagous insects whose year-round prevalence on the island is supported by favorable climatic conditions. The euthanasia of all infected equids within the population is not a feasible strategy when the prevalence of the disease is high or in highly specialized or rare breeds of equid such as the Marajoara horse. Preservation of these animals is complicated by high rates of seropositivity with the potential for vertical transmission or insect mediated transmission following parturition of foal. Therefore, the aim of this study was to evaluate EIAV vertical and post-partum insect-mediated transmission rates among foals born to seropositive feral mares until natural weaning. Serum samples of foals born to seropositive feral mares from Soure municipality, within Marajó Island, were collected to investigate their serological status, using an indirect ELISApgp45 with positive samples being tested in the classical agar gel immunodiffusion (AGID) assay to confirm the results.
Results

Twenty-eight foals were sampled and their serological status was monitored over a 2-year period. Depending on the birth date, some of them were sampled up to six times. All foals remained with their respective mares until fully weaned, approximately 10 months of age, and just 2 of 28 foals (7.14%) in the study group became seropositive against EIAV.
Conclusion

The results showed that in most cases it is possible to obtain negative foals born to and eventually weaned by EIA positive mares, even in equatorial regions where substantial rainfall and high temperatures favor the proliferation of insect vectors.
Amine-grafted Walnut Shell for Efficient Removal Phosphate and Nitrate from Aqueous Solution
Authors: Dovi Evans , Aryee Aaron Albert , Li Jianjun , Li Zhaohui , Qu Lingbo , Han Runping
Published: June 2021

The presence of emerging pollutants such as PO43− and NO3− in water bodies has attracted worldwide concern about their severe effects on water bodies and the health of humankind in general. Therefore, to preserve the health of humankind and environmental safety, it is of the essence that industrial effluents are treated before they are discharged into water bodies. To accomplish this, the walnut shell was functionalized (ACWNS) with amine for effective removal of PO43− and NO3−. Characterization studies of ACWNS were conducted using FTIR, XRD, XPS and BET techniques. Removal of both ions was enhanced at lower temperature (293 K). The maximum uptake capacity of phosphate and nitrate, at 293 K, was 82.2 and 35.7 mg g− 1, respectively. The primary mechanism by which these ions were uptaken onto ACWNS could be electrostatic interactions and hydrogen bonding.Pseudo-second-order kinetics fitted the PO43̶ and NO3− adsorption, while Freundlich and Langmuir models best fitted the PO43̶ and NO3̶ adsorption, respectively. Furthermore, in the binary system, the uptake capacity of phosphate decreased by 14.4% while nitrate witnessed a reduction in its uptake capacity by 10.4 %. So ACWNS has a higher attraction towards both ions and this could be attributed to the existence of a variety of active areas on ACWNS that exhibit a degree of specificity for the individual anions. Results obtained from real water samples analysis confirmed ACWNS as highly efficient to be utilized for practical remediation processes.
Identification and Bioinformatics Analysis of Differentially Expressed Milk Exosomal Micrornas in Milk Exosomes of Heat-Stressed Holstein Cows
Authors: Wang Yue , Fang Jian , Zeng Han-Fang , Li Hui-Xia , Chen Kun-Lin
Published: June 2021

Background
In summer, heat stress is one of the primary reasons for the compromised health and low milk productivity of dairy cows. Hyperthermia affects milk synthesis and secretion in the mammary glands of dairy cows. As molecules for intercellular communication, milk-derived exosomes carry genetic material, proteins and, lipids, playing a crucial role in mammary tissue growth and milk synthesis in dairy cows. The aim of this study was to explore the milk exosomal miRNAs profile of heat-stressed and normal Holstein cows.
Results
We isolated and identified milk exosomes to screening for differentially expressed miRNAs using small RNA sequencing. Then, TargetScan and miRanda algorithms were used to predict the putative targets of the differentially expressed miRNAs, whereas GO and KEGG pathway enrichment analyses were performed for the differentially expressed miRNA-target genes. Our results showed that 215 miRNAs were significantly differentially expressed in heat-stressed milk exosomes, of which one was up-regulated and 214 were significantly downregulated. GO and KEGG enrichment analyses indicated that differentially expressed miRNAs might play a role in apoptosis, autophagy, and the p38 MAPK pathway. qRT-PCR assay verified that the expression of miRNAs was consistent with the sequencing results, warranting further verification of their specific targets of action.
Conclusions
In conclusion, changes in the miRNA expression profile of milk exosomes indicated the role of exosomal miRNAs in regulating heat stress resistance and apoptosis in dairy cows. Our results suggested that milk-derived exosomal miRNAs could increase mammary gland resistance to heat stress, thereby enhancing milk synthesis in dairy cows.
Knowledge and attitude toward ethics committee and ethical research practice among researchers of three sectors: An institutional study in Kuwait
Authors: Shiju Rashmi , Thankachan Smitha , Akhil Ayesha , Sharma Prem , Bennakhi Abdullah
Published: June 2021

Background
Adherence to ethical guidelines in the conduct of research is of paramount importance. This ensures that the research is conducted with integrity which in turn builds trust in the researchers and their results. However, misconduct occurs frequently in the research.
Methods
In this anonymous online cross-sectional survey, researchers from Dasman Diabetes institute were surveyed about their knowledge of and attitude toward ethics committee and research ethics practices across sectors. The study was conducted in November and December 2019 using an online Microsoft forms questionnaire. The questionnaire was divided into five parts including demographics, knowledge of ethical principles and the function of ethics committee, knowledge of ethics and attitudes toward ethics committees and ethical practices. Question-formats were combination of multiple-choice, yes or no, and five-point Likert-scale formats. Researchers applied, the Chi-square test, the Kolmogorov-Smirnov test, ANOVA, the nonparametric Kruskal-Wallis test, the Student’s t-test, and or the Mann-Whitney U test for data analysis.
Results
The study had a response rate of 86%. Among the 55 participants of this study, 43 (78%) had prior training in research ethics. Those with maximum training were from the medical sector (82.4%) followed by the research sector (80.8%) and operations sector (66.7%). Significant association was observed between prior ethics training and different number of projects handled by a respondent. Similar significant association was noted among the trained participants on knowledge and awareness of the role of the ethics committee, ethical principles, the committee’s ways of reviewing protocol and attitude towards consenting process. However, knowledge and awareness of ethics committee and its function varied significantly across sectors and across different number of projects handled. Attitude toward ethical practices such as misconduct and manipulation of data was also found to vary significantly across sectors.
Conclusion
Our study demonstrated that research sector and medical sector were aware of the knowledge and attitude toward ethics committee, its function and research ethical practices in comparison to operations sector. This indicates a gap in knowledge and attitude which can be bridged by continuous and customized ethics training based on the type of research.
Barrier Function-Based Adaptive Integral Sliding Mode Finite-time Attitude Control for Rigid Spacecraft
Authors: Wang Jie , Hu YuShang , Ji Wenqiang
Published: June 2021

This paper investigates the problem of the finite-time attitude tracking control for rigid spacecrafts with external disturbances and inertia uncertainties. Firstly, a finite-time approach is designed to achieve attitude tracking control of the rigid spacecraft in absence of disturbances and inertia uncertainties and the time of convergence can be chosen in advance. Then, the integral sliding mode combined with barrier function-based adaptive laws is proposed to reject the disturbances and inertia uncertainties, and at the same time, a barrier function-based adaptive method can also ensure the solutions of the rigid spacecraft system belonging to a stipulated vicinity of the intended variables starting from the initial moment and the uncertainties' upper bound is not overestimated. Finally, numerical simulation is provided to illustrate the efficiency of the proposed control protocol.
Effects of Low-Intensity Pulsed Ultrasound on Pain and Functional Disability in Patients With Early-Stage Lumbar Spondylolysis: A Randomized Controlled Trial
Authors: Tanveer Fahad , Arslan Syed Asadullah , Darain Haider , Ahmad Ashfaq , Gilani Syed Amir , Hanif Asif
Published: June 2021

Background: Low Intensity Pulsed Ultrasound (LIPUS) is beneficial in accelerating fracture recovery, enhancing their capacity to execute tasks of daily life and, as a result, their autonomy. Methods: Thirty-four (29 males and 5 females) pre-diagnosed patients referred by an orthopaedic surgeon exhibiting symptomatic low back pain for at least four months were recruited and randomly divided into LIPUS group and Routine Physical Therapy (RPT) group. The lottery method was used to randomly assign patients into two groups. Numeric Pain Rating Scale (NPRS) was utilized for the measurement of pain and Oswestry Disability Index (ODI) for functional disability. Patients were assessed at baseline, at the end of 12th and 20 th week. Interventions were applied by the physical therapist having more than eight years of clinical experience for 10 weeks on alternate days. Results: LIPUS group reported greater reduction in pain with mean change of 3.18 points (95% CI: 2.2, 4.2; p < 0.001) at 12 th week, 6.18 points (95% CI: 5.5, 6.8; p < 0.001) at 20th week follow-up and functional disability with mean change of 28.24 points (95% CI: 23.7, 36 32.8; p < 0.001) at 12th week and 39.47 points (95% CI: 31.8, 47.1; p < 0.001) at 20th week follow-up compared with the RPT group.Conclusion: Low-intensity pulsed ultrasound has significantly reduced pain and functional disability in patients with early-stage lumbar spondylolysis and could be preferred as a safe non-invasive treatment method for early bone healing. Trial registration: WHO-Iranian registry of clinical trials (IRCT20200206046396N1, Dated: 02/05/2020).
An Optimal Integration of Multiple Machine Learning Techniques to Real-Time Reservoir Inflow Forecasting
Authors: Huang I-Hang , Chang Ming-Jui , Lin Gwo-Fong
Published: June 2021

A reservoir inflow forecasting system represents a crucial technique in reservoir operation and disaster prevention, particularly in areas where the primary water source derives from typhoon events. This includes the study area of the current research, i.e., the Shimen Reservoir (Taiwan). Effectively depositing short and high-intensity rainfall and avoiding disaster losses present significant challenges in this regard. However, the high variability and uncertainty of such rainfall events make them difficult to forecast using traditional physical-based models, which require too many calculations for application in real-time disaster forecasting. Accordingly, in this study, seven machine learning (ML) algorithms, including three conventional ML and four deep learning algorithms, were compared to derive their effectiveness for reservoir inflow forecasting in extreme weather events. The forecasting lead-times were set to 1, 4, and 6-h, representing short, medium, and long-term forecasting, respectively. Moreover, to ensure the stability and credibility of the models, two types of integrated approaches, ensemble means and switched prediction method (SP) were also employed. The results showed that although an optimal algorithm could be selected for the short, medium, and long-term, individual algorithms did not always perform well in all events. Nonetheless, the integrated approaches can effectively combine the advantages of all the included algorithms and generate more accurate and stable forecasting results, particularly when using SP, which was involved in the top three performances among all typhoon examples and indicated the best average performance. Accordingly, when using a single forecasting algorithm, gated recurrent unit, a type of transformed recurrent neural network, will yield the best performance. Furthermore, integrated forecasts, particularly involving SP, can effectively improve the accuracy and stability of forecasts to render a model more applicable to an actual situation.
MEX3A and MEX3B as Potential Prognostic Indicators in Stomach Adenocarcinoma
Authors: Zou Junwei , Huang Yong , Wu Zhaoying , Xie Hao , Wang Rongsheng , Xing Chungen
Published: June 2021

Stomach adenocarcinoma(STAD) is one of the deadliest cancers in the world. The expression levels of family members of mex-3 RNA that bound MEX3A (member A) and MEX3B (member B) were high expressions in different cancers and interconnected to deficient prognosis. The present research assessed the potential regarding the expression of MEX3A and MEX3B in STAD by analysing the facts of STAD (viz. The Cancer Genome Atlas). TCGA, MEX3A and MEX3B in the cancers were analyzed using TIMER2.0, Kaplan Meier Plotter, and cBioPortal. The data was visualized using version 4.0.3 of R. We found MEX3A and MEX3B had various expressions regarding major cancer and relevant common tissues. Especially, high expression of MEX3A and MEX3B had relationships with the OS (namely overall survival) with deficiency and RFS (viz. relapse-free survival) concerning STAD. The expressions of MEX3B had correlations to T stage with P being 0.012 and to the race with P being 0.049. MEX3B was highly expressed in T3 and T4 stages, and was highly expressed in the white race. MEX3A mutation had a better survival without diseases, with P being 0.0205. However, the situation was different with non-overall survival, with P being 0.194, in comparison with the patients who did not have MEX3A change. MEX3A and MEX3B on tumor pathogenesis might be related to "RNA splicing" and "spliceosomal complex" and "single-stranded RNA binding". We further investigated the association between MEX3A and MEX3B and immune cells. The mast cells of the most connections to MEX3A (R=-0.300, P<0.001) and the NK cells were positively correlation with MEX3B (R=0.590, P<0.001). It showed that they might be potential prognostic molecular biomarkers in patients with STAD.
Long-Term Clinical Results of Trabectome Surgery
Authors: Un Yasemin , Buyukavsar Cihan , Comerter Dogukan , Sonmez Murat
Published: June 2021

Purpose: To analyze the long-term results of trabectome surgery and to characterize risk factors for failure.Method: This is a single-center retrospective study including 66 eyes of 56 patients who underwent trabectome alone (TA) or phacotrabectome (TP) surgeries between 2012-2016. Surgical success was defined as intraocular pressure (IOP) drop by 20% or IOP ≤21 mmHg and no further glaucoma surgery. Risk factors for further surgeries were analyzed with Cox proportional hazard ratio models. Cumulative success analysis of subgroups was completed with the Kaplan Meier analysis.Results: Mean follow-up period was 59.7±14.1 months. During the follow-up period, 15 of 62 (24.2%) eyes had additional glaucoma surgery. The mean preoperative IOP was 26.8±6.5 mmHg. The mean last visit IOP was 18.7±4.5 mmHg (p<0.01). IOP decreased 30.1% from baseline at the last visit. Average numbers of medications used were 3.42 ±0.76 (range 1-4) and 2.45±1.33 (range 0-4) at preoperative and last visit, respectively (p<0.01). The risk factors for further surgery requirements were higher baseline IOP (HR:1.12, p:0.01), higher central corneal thickness (CCT) (HR:1.01, p:0.04), and higher amounts of preoperative drugs (HR:2.22, p:0.08). The cumulative probability of success was 93.5%, 90.5%, 85.5%, 80.6%, and 77.4% at 3, 12, 24, 36, and 60 months, respectively. Kaplan Meier survival plots indicating the time of additional glaucoma surgery in the subgroups showed higher survival probability in primary open angle glaucoma (POAG), males, phacotrabectome cases, early stage glaucoma, and eyes without previous glaucoma surgery. Conclusion: Trabectome success ratio was 50% at 59 months. Higher baseline IOP and thicker CCT are associated with an increased risk of further glaucoma surgery.
Economic Impact of Switching From Partially Combined Vaccine “Pentaxim ® and Hepatitis B” to Fully Combined Vaccine “Hexaxim ® ” in The Malaysian National Immunization Program
Authors: Aljunid Syed Mohamed , Bashir Lama Al , Ismail Aniza Binti , Aizuddin Azimatun Noor , Zafirah S A , Nur Amrizal Muhammad
Published: June 2021

Background: The decision to implement new vaccines should be supported by public health and economic evaluations. Therefore, this study was primarily designed to evaluate the economic impact of switching from partially combined vaccine (Pentaxim® plus hepatitis B) to fully combined vaccine (Hexaxim®) in the Malaysian National Immunization Program (NIP) and to investigate healthcare professionals (HCPs)’ and parents/caregivers’ perceptions.Methods: In this economic evaluation study, 22 primary healthcare centers were randomly selected in Malaysia between December 2019 and July 2020. The baseline immunization schedule includes switching from Pentaxim® (four doses) and hepatitis B (three doses) to Hexaxim® (four doses), whereas alternative scheme includes switching from Pentaxim® (four doses) and hepatitis B (three doses) to Hexaxim® (four doses) and hepatitis B (one dose) administered at birth. Direct medical costs were extracted using a costing questionnaire and an observational time and motion chart. Direct non-medical (cost for transportation) and indirect costs (loss of productivity) were derived from parents/caregiver’s questionnaire. The vaccine societal cost was calculated as cost per dose, per fully immunized child and per birth cohort, and then the net cost savings were calculated upon the total cost of Hexaxim® and Pentaxim® plus hepatitis B. Also, HCPs’ and parents/caregiver’s perceptions were investigated using structured questionnaires.Results: The cost per dose of Pentaxim® plus hepatitis B vs. Hexaxim® was Malaysian ringgit (RM) 31.90 vs. 17.10 (direct medical cost), RM 54.40 vs. RM 27.20 (direct non-medical cost), RM 221.33 vs. RM 110.66 (indirect cost), and RM 307.63 vs. RM 155.00 (total cost). Similar trend was observed for alternative scheme. Compared with Pentaxim® plus hepatitis B, total cost savings per dose of Hexaxim® were RM 137.20 and RM 104.70 in the baseline and alternative scheme, respectively. Conclusions: Incorporation of Hexaxim® within Malaysian NIP is highly recommended because the use of Hexaxim® has demonstrated substantial direct and indirect cost savings for healthcare providers and parents/caregivers with high percentage of positive perceptions, compared with Pentaxim® plus hepatitis B.Trial registration: Not applicable
Unplanned Removal of a Patent Foramen Ovale Closure Device During Retrieval of an Inferior Vena Cava Filter
Authors: Agzarian Marc , Sinhal Ajay
Published: June 2021

This brief communication reports what appears to be the first case of an interaction between an inferior vena cava filter and a patent foramen ovale closure device. During removal of the inferior vena cava filter, the patent foramen ovale closure device was unintentionally removed. This case report serves to highlight the possible interaction of these two devices.
Multipopulational Transcriptome Analysis of Post-Weaned Beef Cattle at Arrival Further Validates Candidate Biomarkers for Predicting Clinical Bovine Respiratory Disease
Authors: Scott Matthew , Woolums Amelia , Swiderski Cyprianna , Perkins Andy , Nanduri Bindu , Smith David , Karisch Brandi , Epperson William , Blanton John
Published: June 2021

Bovine respiratory disease (BRD) remains the leading infectious disease in post-weaned beef cattle. The objective of this investigation was to contrast the at-arrival blood transcriptomes from cattle derived from two distinct populations that developed BRD in the 28 days following arrival versus cattle that did not. 48 blood samples from two populations were selected for mRNA sequencing based on even distribution of development (n=24) or lack of (n=24) clinical BRD within 28 days following arrival. Sequenced reads (~50M/sample, 150 bp paired-end) were aligned to the ARS-UCD1.2 bovine genome assembly. 132 unique DEGs were identified between groups stratified by disease severity (healthy, n=24; treated_1, n=13; treated_2+, n=11) with edgeR (FDR < 0.05). DEGs in treated_1 relative to both healthy and treated_2+ were predicted to increase neutrophil activation, cellular cornification/keratinization, and antimicrobial peptide production. DEGs in treated_2+ relative to both healthy and treated_1 were predicted to increase alternative complement activation, decrease leukocyte activity, and increase nitric oxide production. Receiver operating characteristic (ROC) curves generated from expression data for six DEGs identified in our current and previous studies (MARCO, CFB, MCF2L, ALOX15, LOC100335828 (aka CD200R1), and SLC18A2) demonstrated good-to-excellent predictability for classifying disease occurrence and severity. This investigation identifies candidate biomarkers and functional mechanisms in at arrival blood that predicted development and severity of BRD.
Optimization of An O2-Balanced Bioartificial Pancreas for Type 1 Diabetes Using Statistical Design of Experiment.
Authors: Mouré Anne , Bekir Sawsen , Bacou Elodie , Haurogne Karine , Allard Marie , De Beaurepaire Laurence , Bosch Steffi , Riochet David , Gauthier Olivier , Blancho Gilles , Soulillou Jean-Paul , Poncelet Denis , Mignot Grégoire , Courcoux Philippe , Jegou Dominique , Bach Jean-Marie , Mosser Mathilde
Published: June 2021

A bioArtificial pancreas (BAP) encapsulating high pancreatic islets concentration is a promising alternative for type 1 diabetes. However, the main limitation of this approach is O2 supply, especially until graft neovascularization. Here, we described a methodology to design an optimal O2-balanced BAP using statistical design of experiment (DoE). A full factorial DoE was first performed to screen two O2-technologies on their ability to preserve pseudo-islet viability and function under hypoxia and normoxia. Then, response surface methodology was used to define the optimal O2-carrier and islet seeding concentrations to maximize the number of viable pseudo-islets in the BAP containing an O2-generator under hypoxia. Monitoring of viability, function and maturation of neonatal pig islets for 15 days in vitro demonstrated the efficiency of the optimal O2-balanced BAP. The findings should allow the design of a more realistic BAP for humans with high islets concentration by maintaining the O2 balance in the device.
TBHQ Regulates the Nrf2/HO-1 Pathway to Enhance Stem Cell Treatment of Diabetic Retinopathy
Authors: XU Ze-Peng , TIAN Ni , LI Song-Tiao , LI Kun-Meng , WANG Xiao-Yu , LI Xiao-Jie , DONG Yan , AN Mei-Xia , YU Xiao-Yi , ZHONG Rui-Ying , LIU Qiu-Hong , WANG Xiao-Chuan , YANG Yan , LUO Ying-Zi
Published: June 2021

Objective: To investigate the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on diabetic retinopathy (DR) in diabetic rats, and to study the mechanism of hUCMSCs in treating diabetic retinopathy by tert-butylhydroquinone (tBHQ) regulation of the Nrf2/HO-1 pathway.Methods: The diabetic rat model was induced by intraperitoneal injection of streptozotocin (STZ). The experimental animals were divided into six groups: Normal, diabetes mellitus (DM), hUCMSCs, tBHQ, combined tBHQ-hUCMSCs, and all-trans-retinoid acid (ATRA)-hUCMSCs combined group. Visual function experiments and histological analyses were performed eight weeks post intravitreal injection. Biochemical and molecular analyses were used to assess the hUCMSCs composition and its biological effects.Results: Improvements in systemic oxidative stress and inflammation were found in the tBHQ group. Although hUCMSCs had no significant effect on oxidative stress, retinal structure was improved, visual defects reduced and expression of local retinal inflammatory factors were inhibited following its application. The effect of combined therapy was better than that of single therapy. Inhibition of the Nrf2/HO-1 pathway can promote the expression of systemic inflammatory factors and inhibit the therapeutic effect of hUCMSCs in the retina.Conclusions: Intravitreal administration of hUCMSCs triggers an effective cytoprotective microenvironment in the retina of diabetic mice. Alone, however, it may not significantly improve the systemic inflammatory response of diabetes. In combination with tBHQ it may promote Nrf2expression, systemic antioxidant stress and therapeutic effects of hUCMSCs.
Effects of Grain Shape Genes Editing on Appearance Quality of Erect-Panicle Geng/Japonica Rice
Authors: Mao Ting , Zhu Mingdong , Sheng Zhonghua , Shao Gaoneng , Jiao Guiai , Mawia Amos Musyoki , Ahmad Shakeel , Xie Lihong , Tang Shaoqing , Wei Xiangjin , Hu Shikai , Hu Peisong
Published: June 2021

Background
Long grain geng/japonica rice has a higher market preference due its excellent appearance quality. The dense and erect-panicle 1 (dep1) gene has been widely used in the breeding of high-yielding geng/japonica rice cultivars in China. However, this gene causes short and round grain shape thus making it less attractive in global rice markets. Therefore, breeding of high-yielding long-grain geng/japonica rice cultivars by incorporating dep1 with major-effect grain shape gene is of high priority in rice industry. Up to now, multiple grain shape genes’ effect mechanism has been clearly elaborated, however, under the background of erect-panicle geng/japonica rice, the effect of major grain shape genes on the appearance quality need to be further clarified, as detailed reports are limited.
Findings:
Utilizing CRISPR/Cas9 technology, a series of near-isogenic lines (NILs) (YF47dep1-gw8, YF47dep1-gs3, YF47dep1-gl7, YF47dep1-qgl3 and YF47dep1-tgw6) in Yanfeng 47(YF47dep1) background were created. Grain appearance and yield components analysis showed that: i) All NILs’ grain length to width ratio was significantly increased compared to that of YF47dep1, excepted YF47dep1-gs3, ii) The chalkiness degree was significantly reduced in all of the NILs, iii) In all of the NILs, YF47dep1-gw8 grains exhibited the greatest length to width ratio and the lowest chalkiness degree, iv) The composition of glume cells and filling characteristics of the endosperm were two key factors contributing grain shape and grain chalk variations, respectively, and v) Owning to a substantial increase in the thousand grain weight, the yields of YF47dep1-gs3 and YF47dep1-tgw6 were significantly higher than that of YF47dep1, whereas YF47dep1-qgl3 exhibited the lowest yield because of a dramatic decrease in the effective panicle number and thousand grain weight.
Conclusions
All the results revealed that pyramiding dep1 with major-effect grain shape alleles was an effective approach to improving the appearance quality of erect-panicle geng/japonica rice, owning to both of the appearance quality and yield improvement, GS3 and TGW6 alleles can be applied directly for breeding long-grain shape geng/japonica rice, and editing GW8 resulted in excellent appearance quality but low yield, therefore, this gene would be difficult to use directly but can be considered as the core germplasm resource.
An Investigation of Neonatal Mortality and its Main Risk Factors in Hospitalized Late Preterm Infants
Authors: Basiri Behnaz , sadeghian zohre , Pezeshki Nasrollah , Rabie Mohammad Ali Seif , lakpour Tara
Published: June 2021

Background: Late preterm infants are born at a gestational age between 34+1 and 36+6 weeks, they have higher morbidity and mortality rates than term infants (gestational age ≥37 weeks). Methods: In this retrospective, cross-sectional study the medical records of late preterm infant hospitalized in Fatemieh hospital, Hamadan- Iran, were extracted during a one-year period (March 2018– March 2019). Demographic information including sex, birth weight, causes of hospitalization and complications of the disease, length of stay, and outcome were assessed. Results: Out of 150 infants studied in this research, 52% were female and 48% were male. Mean weight was 2775±572 gr with mean admission days of 9.1±4.7 days. Respiratory distress syndrome (RDS) was the most common cause of admission (80.7%). Neonatal mortality rate was overall 7.3%. According to logistic regression, need for resuscitation and ventilation, central nervous system (CNS) involvement (seizure) (P≤0.001), congenital heart disease (P≤0.001), need to surfactant administration (P=0.034), pneumonia (P=0.018), feeding problems (P≤0.001), hypoglycemia (P=0.048) and septicemia (P≤0.001), could all possibly correlate with the occurrence of death in late-preterm infants.Conclusion: Neonatal mortality is high in late preterm infants and can be predicted by the need to intensive supports for respiratory distress syndrome, CNS involvement, congenital heart disease, and septicemia.
Comparison of Bacterial Communities from the Surface and Adjacent Bottom Layers Water of Billings Reservoir
Authors: Marcondes Marta Angela , Nascimento Andrezza , Pessôa Rodrigo , Victor Jefferson Russo , Duarte Alberto José da Silva , Sanabani Sabri Saeed
Published: June 2021

Here, we describe the microbial diversity and physicochemical properties in freshwater samples from the surface and bottom layer of Billings reservoir in São Paulo state, Brazil. Twenty-two matched samples were characterized using the 16S rRNA gene Illumina MiSeq platform. Taxonomical composition revealed an abundance of Cyanobacteria phyla, followed by Proteobacteria, with 1903 and 2689 known bacterial genera in the surface and deep-water layers, respectively. Shannon diversity index ranging from 2.3 - 5.39 and 4.04 - 6.86 in the surface and bottom layer, respectively. Among the 120 pathogenic genera identified, Flavobacterium was the most predominant genus. Temperature and phosphorus concentration were the most influential factors in shaping the microbial communities of both layers. Predictive functional analysis suggests that the reservoir is enriched in motility genes involved in the flagellar assembly. The overall results present new information on the significantly altered diversity composition of the bacterial community detected in Billings freshwater reservoir.
Hydroxychloroquine for Treatment of COVID‐19 Patients: a Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Moraes Vinícius Y , Marra Alexandre R , Matos Leandro L , Neto Ary Serpa , Rizzo Luiz Vicente , Neto Miguel Cendoroglo , Lenza Mário
Published: June 2021

Background: We performed a systematic review of the literature and meta-analysis on the efficacy and safety of hydroxychloroquine to treat coronavirus disease 2019 (COVID-19) patients. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and LILACS (2019 to March 2021) for patients aged 18 years or older, who had COVID-19 and were treated with hydroxychloroquine versus placebo or standard of care. We also searched the WHO Clinical Trials Registry for ongoing and recently completed studies, and the reference lists of selected articles and reviews for possible relevant studies, with no restrictions regarding language or publication status. Random-effects models were used to obtain pooled mean differences of treatment effect on mortality, and serious adverse effects between hydroxychloroquine (HCQ) and the control group (standard of care or placebo); heterogeneity was assessed using the I2 and the Cochran´s Q statistic. Results: Nine studies met the inclusion criteria and were included in the meta-analysis. There was no significant difference in mortality rate between patients treated with HCQ compared to standard of care or placebo (16.7% vs. 18.5%; pooled risk ratio 1.09; 95%CI: 0.99-1.19). Also, therate of serious adverse effects was similar between both groups, HCQ and control (3.7% vs. 2.9%; pooled risk ratio 1.22; 95%CI: 0.76-1.96). Conclusion: Hydroxychloroquine is not efficacious in reducing mortality of COVID-19 patients.Systematic review registration: Prospero database, registration number: CRD42020197070.
Event-Triggered Control and Application for A Class of Nonlinear Multi-Agent Systems With Time Delay
Authors: Zhang Jiancheng , Wang Xinsheng , Cao Qi
Published: June 2021

Linear multi-agent systems (MAS) have been studied a lot. Since nonlinear MAS with time delay and directed graph by using the event-triggered technique are seldom studied, the distributed control of a class of nonlinear leader-following MAS is considered in this paper. Firstly, we linearize the nonlinear MAS composed of N agents with directed graph by feedback, and transform the research object into a linear system. Furthermore, we proposed an event-triggered consensus algorithm for the leader-following MAS. Then we prove the consensus of the proposed algorithm by using related theorems. It is proved that the algorithm converges exponentially and avoids Zeno-behavior of triggering time sequences. Finally, we apply the designed event-triggered consensus algorithm to an engineering example. A simulation system is established in Matlab environment and the simulation example results verify the effectiveness of the proposed algorithm. It effectively reduces the number of communication among agents and achieves the consistency of control objectives.
Engineering Resistance Against Cotton Leaf Curl Kokhran Virus-Burewala Strain Using CRISPR-Cas9 System in Nicotiana Benthamiana
Authors: Hamza Muhammad , Khan Muhammad Zuhaib , Mustafa Roma , Kamal Hira , Hussain Aneela , Mansoor Shahid , Amin Imran
Published: June 2021

Clustered regularly interspaced palindromic repeats (CRISPR) and associated Cas9 nuclease (CRISPR-Cas9) systems provide adaptive immunity to prokaryotes against infectious phage particles that can be engineered as a genome-editing tool. Guided by an RNA strand, the class II type II CRISPR-Cas9 system can be employed to provide resistance against plant DNA viruses. Here we describe an efficient CRISPR-Cas9 genome editing system based on simultaneous targeting of the highly conserved intergenic region (IR) of the virus that can provide resistance against Cotton leaf curl Kokhran virus-Burewala strain (CLCuKoV-Bur) in Nicotiana benthamiana plants. The data revealed that upon infection, the transgenic plants harboring CRISPR-Cas9 and two gRNAs showed complete resistance against CLCuKoV-Bur/Cotton leaf curl Multan betasatellite (CLCuMB). All efforts failed to find the intact virus in CLCuKoV-Bur/CLCuMB challenged transgenic (OX:Cas9NB:IR) plants using either gene specific PCR primers or CLCuKoV-Bur as a probe in southern blot hybridization. Thus, our results have demonstrated an efficient CRISPR-Cas9 approach to engineer durable resistance against CLCuKoV-Bur in a model system. The implications of these findings are discussed.