bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Evaluation of a Novel Fast Broad-Range ITS/LSU DNA PCR and Sequencing Assay (FBR-PCR/S) for Rapid Diagnosis of Invasive Fungal Diseases: Multi-Year Experience in a Large Canadian Healthcare Zone and a Literature Review
Authors: Chow B , Groeschel M , Carson J , Griener Thomas , Church Deirdre
Published: November 2021

BackgroundThis study evaluated the performance of a novel fast broad range PCR and sequencing (FBR-PCR/S) assay for the improved diagnosis of invasive fungal disease (IFD) in high-risk patients in a large Canadian healthcare region.MethodsA total of 114 clinical specimens (CS) including bronchoalveolar lavages (BALs) were prospectively tested from 107 patients over a 2-year period. Contrived BALs (n=33) inoculated with known fungi pathogens were also tested to increase diversity. Patient characteristics, fungal stain and culture results were collected from the laboratory information system. Dual-priming oligonucleotide (DPO) primers targeted to the ITS (~350 bp) and LSU (~550 bp) gene regions were used to perform FBR-PCR/S assays on extracted BALs/CS. The performance of the molecular test was evaluated against results of fungal stains and culture, and where available, histopathology, and clinical review for the presence of IFD.ResultsThe 107 patients were predominantly male (67, 62.6%%) with a mean age of 59 yrs. (range = 0 to 85 yrs.): 74 (69.2%) patients had at least one underlying comorbidity: 19 (34.5%) had confirmed and 12 (21.8%) had probable IFD. Culture recovered 66 fungal isolates from 55 BALs/CS with Candida spp. and Aspergillus spp. being most common. For BALs, the molecular assay vs. fungal culture had sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), and efficiency of 88.5% vs.100%, 100% vs. 61.1%, 100% vs. 88.5%, 61.1% vs. 100%, and 90.2% for both. For other CS, the molecular assay had similar performance to fungal culture with sensitivity, specificity, PPV, NPV and efficiency of 66.7%, 87.0%, 66.7%, 87.0% and 81.3% for both methods. Both methods also performed similarly, regardless of whether CS stain/microscopy showed yeast/fungal elements. FBR-PCR/S assays results were reported in ~8h compared to fungal cultures that took between 4 to 6 weeks.ConclusionsRapid molecular testing compared to culture has equivalent diagnostic efficiency but improves clinical utility by reporting a rapid species-level identification the same dayshift (~8h).
Development of High Intensity Interval Training (HIIT) for Reactive Agility Tennis: Literature Review and Validity of Aiken
Authors: Alim Abdul , Tomoliyus Tomoliyus , Fauzi Fauzi , Ariani Nevita , Widodo Hary
Published: November 2021

Background

The purpose of this study was to examine High Intensity Interval Training (HIIT) for Reactive Agility Tennis with a literature review approach and develop HIIT for Reactive Agility Tennis with Aiken validation.
Methods

This research method consists of two stages: the first stage using the Literature review method and the second stage is Aiken validation. In the first stage, the participants of this research used documents. Data collection through the Pubmed database, and Google Scholar, used the PRISMA. Data analysis uses thematic analysis through three stages. The second stage is validating the HIIT model for Reactive Agility Tennis. The participants of this study used eight experts. Data analysis using the Aiken formula.
Results

the results of previous research on HIIT for reactive agility tennis found similarities, namely in general, using high intensity, a minimum number of eight types, training frequency at least 3 times per week, whereas in general the difference in training intervals, the type of HIIT exercise in previous studies for Increases reactive tennis agility. In addition, there are very few HIIT studies for reactive agility in tennis. Therefore, it is necessary to develop HIIT for reactive agility tennis. The second stage of this research has found a high validity of Aiken value in the development of HITT for reactive agility tennis.
Conclusions

HIIT highly increasing reactive tennis agility, therefore, HIIT can be used by coaches to increase tennis athletes' reactive agility, and further research needs to be done.
Systematic Review registrations:
SYSR-D-21-00999
Examining the place of the Female Condom in India’s Family Planning Program: A qualitative investigation of the attitudes and opinions of key stakeholders in Pune, India
Authors: Weerasinghe Medhavi , Agawane Shubhangi , Karandikar Neelima , Fisher Jane , Sastry Jayagowri
Published: November 2021

Background: With overpopulation contributing to the depletion of planetary resources, the high rates of unintended pregnancies in India are a cause for concern. Despite the free supply of contraception options within India’s national family planning initiatives, women are generally offered hormonal options as temporary spacing methods. However, female condoms, a much neglected but potent women initiated, non-hormonal multipurpose prevention device, are yet to be considered for inclusion in India’s contraceptive cafeteria. Thus, we aim to examine the place of female condoms among the contraceptive options, by analysing the perceptions of key stakeholders regarding its advantages and disadvantages, along with their opinions on how female condoms should be promoted.Methods: We used purposive sampling to recruit and interview potential users and dispensers of the female condom. The interview participants visited or worked at family planning clinics in Pune at Smt. Kashibai Navale Medical College and General Hospital (SKNMC-GH), its urban and rural outreach clinics, and at Saheli (a non-governmental organisation for female sex workers). We conducted semi-structured interviews and coded our data inductively. Results: We interviewed 5 rural women, 20 urban women (including 10 female sex workers), 5 male partners of female sex workers, and 5 family planning healthcare providers. Nearly half (12/25) of the women we interviewed, said that they were eager to use female condoms in the future. Many participants perceived female condoms to be an instrument to empower women to be in control of their sexual and reproductive lives (15/35), and that it provided user comfort and confidence (4/35). Their perceived disadvantages are that they are relatively more expensive (6/35), users have limited experience (9/35), and women who buy or use them may be stigmatised and feel embarrassed (4/35). Yet, nearly three-quarters of potential users (21/30) and most healthcare providers (4/5), were confident that female condoms could become popular following extensive promotional campaigns, interventions to improve availability and access, and initiatives to enhance the knowledge of female users. Conclusions: Female condoms have garnered support from both users and dispensers and have the potential to be widely adopted in India if family planning initiatives which increase awareness, knowledge, and access are systematically undertaken as with other contraceptive options.
Ventilatory Ratio is a Valuable Prognostic Indicator in a Representative Observational Cohort of Patients with Acute Respiratory Distress Syndrome
Authors: Siegel Emily R. , Zhuo Hanjing , Sinha Pratik , Papolos Alexander I. , Ni Siyuan A. , Vessel Kathryn , Belzer Annika , Minus Emily B. , Calfee Carolyn S. , Matthay Michael A. , Wick Katherine DesPrez
Published: November 2021

Background Estimating mortality risk is essential for prognostic enrichment. How various indices specific to respiratory compromise contribute to prognostication in patients with acute respiratory distress syndrome (ARDS) is not well-characterized in general clinical populations. The primary objective of this study was to identify variables specific to respiratory failure that add prognostic value to indicators of systemic illness severity. We tested the added benefit of respiratory variables in a representative observational cohort of patients with ARDS.Methods 50 patients with ARDS were enrolled in a single-center, prospective, observational cohort. We tested the contribution of respiratory variables (oxygenation index, ventilatory ratio [VR], and the radiographic assessment of lung edema score) to logistic regression models of 28-day mortality adjusted for indicators of systemic illness severity (the Acute Physiology and Chronic Health Evaluation [APACHE] III score or severity of shock as measured by the number of vasopressors required at baseline). We also compared a model utilizing APACHE III with one including baseline number of vasopressors using the areas under their receiver operating curves.ResultsVR significantly improved model performance by likelihood ratio testing when added to APACHE III (p = 0.04) or vasopressor number at baseline (p = 0.01). Adjusted for APACHE III, each 0.5-unit change in VR was associated with an odds ratio for 28-day mortality of 1.78 (95% CI = 0.78-3.23). The number of vasopressors required at baseline had similar prognostic discrimination to the multi-component APACHE III. A model including the number of vasopressors and VR (area under the receiver operating curve [AUROC] 0.77, 95% CI 0.64-0.90) was comparable to a model including APACHE III and VR (AUROC 0.81 (95% CI 0.68 – 0.93), p value for comparison = 0.58.) ConclusionsIn this observational cohort of patients with ARDS, the ventilatory ratio significantly improved discrimination for mortality when combined with indicators of severe systemic illness. Additionally, the number of vasopressors required at baseline and APACHE III had similar discrimination for mortality when combined with VR. The ventilatory ratio is easily obtained at the bedside and offers promise for both clinical prognostication and enriching clinical trial populations.
Optimizing the Mean and Variance of Bead Geometry in the Wire + Arc Additive Manufacturing Using a Desirability Function Method
Authors: Cho Jin-Soo , Lee Dong-Hee , Seo Gi-Jeong , Kim Duck-Bong , Shin Seung-Jun
Published: November 2021

Wire + arc additive manufacturing (WAAM) is an arc welding process that uses non-consumable tungsten electrodes to produce the weld. The material used in this study is a titanium, carbon, zirconium, and molybdenum (TZM) alloy that is physically and chemically stable and has good performance for use as a welding and high-temperature heating element. However, the price is higher than that of other materials. Because welding cannot be modified after manufacturing, economic losses are high in the case of a defective product. Therefore, it is important to find the best welding settings for the target bead geometry during welding. In this study, welding experiments are designed based on a central composite design, and single-layer WAAM is performed using a TZM material. Consequently, we obtain 17 beads and measure the height, width, as well as left and right toe angles, which represent the geometry of the beads. Based on the measured geometry, we obtain the optimal settings for the WAAM parameters whereat the mean of each geometry is close to its target value and its variance is minimized by using a desirability function method. Furthermore, we conduct additional experiments to validate the optimal settings that we obtain. We compare the predicted and actual geometry values and find that they are quite close. This result indicates that valid optimal settings for the process parameters can be obtained via the proposed method.
Resolving User Conflicts in Multi-user Context-aware Home Environment
Authors: Aljawarneh Mahmoud , Dhomeja Lachhman Das , Malkani Yasir Arafat , shah shahid munir
Published: November 2021

Context-awareness is an enabling technology of pervasive computing that allows applications to adapt themselves in responseto contexts (e.g. activity, location, temperature level, etc.). However, an issue of user conflicts in context-aware applicationsmay arise when multiple users want to access the same application. Our research focuses on this issue and proposes aconflict resolution approach that resolves the conflicts in context-aware home applications. The proposed approach takes intoconsideration the users’ special case contexts (e.g. illness of user) along with their priorities and preferences. The proposedapproach is also useful in cases where multiple users with multiple special cases try to access one application or service.To show the usefulness of the proposed approach, we have integrated the proposed conflict manager with the UbiREAL, asimulated context-aware home environment. The conflict manager utilizes different strategies and different approaches toresolve user conflicts according to the involved situation to suit the need of the family. The prototype evaluation shows thatthe users are satisfied with the proposed system and suggests that the use of users’ special case contexts in detecting andresolving the user conflicts is essential and necessary in the context-aware smart home environments.
The Effect of Particle Size on the Absorption of Cyclosporin A Nanosuspension Through the Gastrointestinal Barrier
Authors: Sun Wenjun , Gao Jing , Fan Ranran , Zhang Ting , Tian Yang , Wang Zengming , Zhang Hui , Zheng Aiping
Published: November 2021

Background: The particle size is one of great important properties of nanoparticles which affects the dissolution rate in vitro and pharmacokinetics in vivo. This study aimed to design an oral cyclosporin A nanosuspension (CsA-NS) and investigate the effect of particle size of cyclosporin A nanosuspension (CsA-NS) on absorption through the gastrointestinal barrier.Results: CsA-NSs with different particle sizes were prepared. Dissolution rate in vitro, transmembrane permeation, gastrointestinal transport properties and the oral absorption of CsA-NSs were promoted by reducing size, except cellular uptake. Specially the particle size of CsA-NSs was nanoscale, their bioavailability was bioequivalent with marked soft capsules (Sandimmun Neoral®) which is self-microemulsion. Conclusions: This study proposed the potential of developing CsA oral multi dosage form, taken the advantage of nanosuspensions.
Rapidly quantitative antimicrobial susceptibility testing for Klebsiella pneumoniae using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry under optimal conditions
Authors: Zhang Anran , Chen Qianqian , Dong Yulan , Tian Bin , Li Jing , Hu Zhidong
Published: November 2021

Background
Klebsiella pneumoniae infections, especially Carbapenem-resistant Klebsiella pneumoniae (CRKP), have become an “Urgent Threats” with high morbidity and mortality. Therefore, rapidly determining of the susceptibility and timely choosing an appropriate antibiotic were the important premises of the treatment of Klebsiella pneumoniae infections. The present study was first to explore the fitness of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) in quantitative rapid antimicrobial susceptibility testing (RAST) with optimal conditions.
Methods
Firstly, we optimized the methodology based on the formic acid extraction method. Taking broth micro-dilution method (BMD) as a reference method, we utilized 25-fold, 50-fold and 100-fold dilutions matching with appropriate incubation time to evaluate the consistency of minimum inhibition concentration (MIC) values derived from BMD and MALDI-TOF MS. Finally, the performances of optimal dilution and incubation time were verified through the reproducibility on different three days.
Results
Directly incubated in the EP tubes and skipped the washing step can not only simplify the procedure, but reduce the unnecessary loss of bacteria biomass to improve sensitivity. The optimal volumes of 70% formic acid/100% acetonitrile (FA/ACN) and supernatant on the target plate were 3 µL and 2 µL, respectively. Comparing the different combination, 25-fold dilution of the 0.5 McFarland suspension and 2hr incubation time resulted in best performance. The consistency between the MS-MIC and corresponding BMD-MIC values in CRKP and Carbapenem-susceptible Klebsiella pneumoniae (CSKP) strains accounted for 76.67% and 66.67%, respectively, which generated the substantial agreements between MS-MIC and BMD-MIC values for CRKP strains (Kappa=0.643) and the moderate agreements for CSKP strains (Kappa=0.476). Finally, the MALDI-TOF MS-based RAST showed a well repeatability.
Conclusion
Considerable potentials were demonstrated for universal and mechanism-indepent RAST by MALDI-TOF MS with optimal conditions, which strengthened its application in accelerating reporting time and clinical diagnosis.
Accurate Prediction Model - Polygenic Risk Score for High-Risk Individuals Predictive of Gastric Cancer
Authors: Duan Fujiao , Song Chunhua , Wang Peng , Ye Hua , Dai Liping , Zhang Jianying , Wang Kaijuan
Published: November 2021

Background

The genetic variation of gastric cancer has not been fully identified. We aimed to screen and identify common variant single nucleotide polymorphisms (SNPs) and long noncoding RNA (lncRNA) related SNPs associated with the risk of gastric cancer, and construct and evaluate prediction models based on polygenic risk score (PRS).
Methods

Non-genetic factors such as H.pylori infection, environment, and genetic factors associated with gastric cancer were screened following meta-analysis and bioinformatics,verified by frequency matched case-control study. PRS and weighted genetic risk scores (wGRS) were derived from estimation of effect size. Net reclassification improvement (NRI), integrated discrimination improvement (IDI), akaike information criterion (AIC) and bayesian information criterion (BIC) were used to evaluate model.
Results

A risk gradient was observed across quantile of the PRS, the results showed that the risk of gastric cancer in the highest 10 quantile of PRS was 3.24 folds higher than that of the general population (OR=3.24,95%CI: 2.07, 5.06). The PRS with one or more risk factors (smoking, drinking and H. pylori infection) was superior to the single genetic risk model. For NRI and IDI, the PRS combinations were significantly improved compared to wGRS model combinations (P<0.001). The model of PRS combined with lncRNA SNPs, smoking, drinking and H. pylori infection was the best fitting model (AIC=117.23, BIC=122.31).
Conclusion

Our findings indicated that the model based on PRS combined with lncRNA SNPs, smoking, drinking, and H. pylori infection had the optimal predictive ability on the risk of gastric cancer, contributing to distinguish high-risk groups from population.
Vertical Plane Buoyant Jets and Fountains in a Uniform Stagnant Ambient Revisited
Authors: Minos Panagiotis , Papanicolaou Panos N.
Published: November 2021

Planar, vertical buoyant jets are of particular interest, both for research and practical purposes for being related to the disposal of the effluent from wastewater treatment plants or saline, a by-product from desalination plants into a body of stagnant fluid. Analytical, closed form solution is derived for plane buoyant jets based on a buoyant jet width parameter proposed by List and Imberger (1973), and compares to earlier laboratory experiments satisfactorily. The derived entrainment coefficient as a function of the local Richardson number of the flow, takes two asymptotic values for jet-like and plume-like flows, while in fountains it takes values lower than that in jets. Laboratory experiments were performed to measure the penetration height of vertical plane fountains with initial Froude number in the range 20 to 130 using shadowgraph and Planar Laser Induced Fluorescence (PLIF) techniques. Interest was focused on the maximum and terminal, steady-state penetration height before the flow direction reversed. The flow was found to be in a state of unstable equilibrium, as it deviated from the vertical axis, swinging on either side. The equations of motion have been solved numerically using the derived entrainment coefficient function, and the results are congruent to earlier and present experiment for vertical fountains.
Tactics for using a Mobile Robot to Recover an Overturned wheeled Vehicle
Authors: Ikeda Hidetoshi , Atoji Shinya , Amemiya Manami , Tajima Shingo , Kitada Takayoshi , Fukai Kotaro , Sato Keisuke
Published: November 2021

This paper describes mobile robot tactics for recovering a wheeled vehicle that has overturned. If such a vehicle were to tip over backward off its wheels and become unable to recover itself, especially in areas where it would be difficult for humans to enter and work, total working efficiency could decline significantly, not only because the vehicle is no only able to perform its job, but because it becomes an obstacle to other work. Herein, we propose a robot-based recovery method that can be used to recover such overturned vehicles and demonstrates its utility. The recovery robot, which uses a mounted manipulator and hand to recover the overturned vehicle, is also equipped with a camera and a personal computer (PC). The ARToolKit software package installed on the robot-mounted PC detects ARmarkers attached to the overturned vehicle and uses the information they provide to orient itself in order to perform recovery operations. To facilitate these ARToolKit-based operations, it is necessary to conduct a theoretical analysis to clarify the distance between the robot manipulator and vehicle, and thus achieve an objective position for grasping the overturned vehicle. The experimental results obtained in this study demonstrate the effectiveness of our proposed system.
Cacoepy (bad pronunciation or mispronunciation) of scientific terms and their effect on learning of secondary level science students
Authors: Rasheed Arsalan , Shahzadi Anita
Published: November 2021

This research investigates cacoepy of science terminology encountered by the secondary level school students of Kohat district. The problem of cacoepy of scientific terms needs investigation due to the assumption that mispronunciations if learned in secondary level were still frequently performed by the advanced level students or may be throughout their life. The current research was designed in order to identify the cacoepy of common science terminologies by secondary school students and to study the science teachers’ views on secondary level science textbooks produced by the Khyber Pakhtunkhwa Textbook board. It was found that majority of the students like science subjects and find the terminologies difficult in which most of the terms contain more than 7 alphabets and were considered as complex terms. Due to this complexity, students feel difficulty in learning of scientific terms. Most of science terms were derived from Greek, Latin and other ancient languages, so students cannot understand their meanings. Almost every chapter of secondary school biology, chemistry and physics is overloaded with difficult terms and students felt difficulty in preparation of those subjects in which mostly difficult terms were found in biology. Mostly science teachers emphasize goals for school science that are directed only toward preparing students for the next academic level (for further formal study of science) and finishing his course within session ignoring the students` pronunciation of scientific terminologies. It is recommended that authors should use simple terms and avoid terms containing more than 7 alphabets. It is important to expose the students of secondary level to such a workload which is appropriate for their studying needs instead of annual books`s revision and insertion of high workload. Teachers should insert few terms into science lessons for practising daily, and it is enough to devote a minute or two to some pronunciation issue so that fluency during lecture is not interrupted a lot. Pointing out a pronunciation problem when it has just arisen in the course is a good way of introducing correct pronunciation into the class. English plays an important part in the development of students because of its present and future as an international language. Real life activities or examples should be associated with important topics. Textbooks should be altered for language of explanation to match the level of students in secondary schools in Khyber Pakhtunkhwa, and some outdated themes should be replaced with new themes to meet the needs of the 21st century. It is suggested that the textbook board in Khyber Pakhtunkhwa should include the urdu phonology and meaning of the found terminologies at the start of each chapter.
GSTT1 and GSTM1 Polymorphisms with Human Papillomavirus Infection in Women from Southern Brazil: A Case-control Study
Authors: Bortolli Ana Paula Reolon , Vieira Valquíria Kulig , Treco Indianara Carlotto , Pascotto Claudicéia Risso , Wendt Guilherme Welter , Lucio Léia Carolina
Published: November 2021

Background Some important factors for the most common sexually transmitted infection (STI) in the world caused by human papillomavirus (HPV) are well defined as early sexual activity, use of contraceptives, tobacco smoking, immunological and genetic factors. This study aimed to investigate the relationship between polymorphisms, GSTM1 and GSTT1, and HPV infection and associated risk factors in a group of women assisted in the public health system in southwestern Paraná, Brazil. Methods and results A case-control study was designed, in which the case group consisted of 21 women with HPV, matched by age, with the control group, 84 women without the virus. Viral detection was conducted via Polymerase Chain Reaction (PCR) and GSTM1 and GSTT1 genotyping by Multiplex PCR. The results showed that the GSTT1 null allele was a protective factor against infection (ORadj: 0.219; 95% CI 0.078-0.618; p=0.004). No relationship was observed for the GSTM1 gene. The smoking habit was defined as a risk factor (ORadj: 3.678; 95% CI 1.111-12.171; p=0.033), increasing the chance for the presence of HPV by up to 3.6 times.Conclusion In short, this study showed in an unprecedented way, the relationship between GSTM1 and GSTT1 genetic polymorphisms and HPV. The relationship found portrays protection from viral infection and not from susceptibility in the female population of southern Brazil.
KDM3A is a Positive Regulator of Cardiac Fibroblasts Conversion that Increases Smad3 Phosphorylation Following TGFβ1 Stimulation
Authors: Liu Xiaopei , Jining Zhou , Zhang Bofang , Liu Gen , Hu Qi , Chen Jing
Published: November 2021

The epigenetic molecule KDM3A has been shown to be involved in improving cardiovascular diseases, but its effect on cardiac fibroblasts (CFs) remains unclear. Thus, we designed the gain- and loss-of-function experiments to investigate the biological functions of KDM3A in cardiac fibroblasts (CFs). Moreover, we added a SIS3-HCL (a specific inhibitor of p-Smad3) to explore the underlying mechanism. The cells viability and migration were verified by CCK-8 and cell migration experiments, respectively, and the degree of fibrosis was measured by Western blot analysis. Our data reveal that KDM3A enhance the proliferation and migration of cardiac fibroblasts, meanwhile, increasing the fibroblast-to-myofibroblast transition, while enabling Smad3 phosphorylation response to TGFβ1 stimuli. However, these results could be abolished by SIS3-HCL, an inhibitor of the p-Smad3. Furthermore, KDM3A inhibition obviously protect cardiac fibroblasts conversion against TGFβ1 stimuli. These results identify that KDM3A may be a novel regulator of the cardiac fibroblasts conversion, through its ability to modulate phosphorylation of Smad3 following TGFβ1 stimuli.
Aptamer Based Point of Care Diagnostic for the Detection of Food Allergens
Authors: Stidham Sarah , Villareal Valerie , Chellappa Vasant , Yoder Lucas , Alley Olivia , Shreffler Wayne , Spergel Jonathan , Fleischer David , Sampson Hugh , Gilboa-Geffen Adi
Published: November 2021

Aptamers, due to their small size, strong target affinity, and ease of chemical modification, are ideally suited for molecular detection technologies. Here, we describe successful use of aptamer technology in a consumer device for the detection of peanut antigen in food. The novel aptamer-based protein detection method is robust across a wide variety of food matrices and sensitive to peanut protein at concentrations as low as 12.5 ppm (37.5 µg peanut protein in the sample). Integration of the assay into a sensitive, stable, and consumer friendly portable device will empower users to easily and quickly assess the presence of peanut allergens in foods before eating. With most food reactions occurring outside the home, the type of technology described here has significant potential to improve lives for children and families.
Triptolide’s anti-inflammatory effects on ARDS by down-regulating miR-9-5p and up-regulating LRG1 and CLDN5
Authors: Han Junyong , Que Huiqing , Li Wei , Xue Shijie , Lin Sui , chen gang
Published: November 2021

Background
Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory disease and its treatment is not fully established. Triptolide, one of Tripterygium wilfordii’s main active components, has been proved to alleviate Lipopolysaccharide (LPS)-induced ARDS. Imbalance of MicroRNAs (miRNAs) is recognized as the pathogenic mechanism of various diseases, including ARDS. However, the specific miRNAs that play a key regulatory role in the anti-inflammatory effect of triptolide in ARDS remain elusive.
Methods
In this study, we administered triptolide in a mouse model of ARDS, and whole transcriptome sequencing was applied to identify meaningful miRNAs and validate them in vitro.
Results
The results showed that triptolide may reduce the inflammatory response in ARDS by regulating miR-9-5p. The data further proved that LRG1 and CLDN5 expression are regulated by miR-9-5p, and triptolide can down-regulate the expression of miR-9-5p by regulating negatively the expression of LRG1 and CLDN5.
Conclusion
Our study revealed that miR-9-5p was the specific miRNAs that plays key role in triptolide’s alleviation of ARDS inflammation by regulating target genes, and its inhibitory effect on LRG1 and CLDN5 expression was verified.
Meiotic Aberrations Leading To Aneuploidy In Cauliflower (Brassica Oleracea L. var. Botrytis)
Authors: Ji Xianwen , Lelivelt Cilia , Wijnker Erik , de Jong Hans
Published: November 2021

Aneuploid cauliflower plants (Brassica oleracea L. var. botrytis) display abnormal curd phenotypes causing serious commercial problems in offspring populations. Despite extensive breeding efforts, selection of genotypes producing euploid gametes remains unsuccessful due to unknown genetic and environmental factors. To reveal the origin of aneuploid gametes, we analyzed chromosome pairing, chiasma formation and chromosome segregation in pollen mother cells of selected cauliflower genotypes. To this end we compared different genotypes exhibiting Low with < 5%, Moderate with 5-10% and High with > 10% aberrant offspring. Microscopic observations revealed regular chromosome pairing at pachytene. However, cells at diakinesis and metaphase I showed variable numbers of univalents, suggesting that chiasma formation during meiotic prophase is incomplete or disrupted and results in a partial desynaptic phenotype. Cells at anaphase I – telophase II exhibited various degrees of unbalanced chromosome numbers explaining the aneuploid offspring. Immunofluorescence probed with an MLH1 antibody demonstrated fluorescent foci in all genotypes, but their lower numbers do not correspond to the putative sites of chiasmata. Interchromosomal connections between chromosomes and bivalents are common at diakinesis and metaphase I, and they contain centromeric and 45S rDNA tandem repeats, but such threads seemed not to affect proper disjoin of the half bivalents at anaphase I. Moreover, male meiosis in the arabidopsis APETALA1/ CAULIFLOWER double mutant with the typical cauliflower phenotype did show interchromosomal connections, but there were no indications for partial desynapsis. We now hypothesize that the occurrence of desynapsis in cauliflower is a developmental out-of-phase phenomenon partially or completely controlled by genes involved in flower and curd development.
MELD 3.0 Score For Predicting Survival in Patients With Cirrhosis After Transjugular Intrahepatic Portosystemic Shunt Creation
Authors: Song Jinlei , Wang Xiaoze , Yan Yuling , Xiang Tong , Luo Xuefeng
Published: November 2021

Background/purpose: Evaluate the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in patients with cirrhosis is important and challenging. To validate the Model for End-Stage Liver Disease (MELD) 3.0 score in predicting mortality in patients with cirrhosis after TIPS creation.Methods: A total of 885 consecutive patients with cirrhosis from December 2011 to October 2019 who underwent TIPS placement were retrospectively reviewed. The prognostic value of the MELD 3.0 score, MELD score, MELD-Na score and Child-Pugh score was calculated and compared with Receiver operating characteristic (ROC) curve and DeLong et al. test.Results: The AUROC of the MELD 3.0 score in predicting 3-month mortality was 0.732 (0.702-0.761), which were significantly superior to the MELD score (0.671 [0.639-0.702]; P = 0.019) and MELD-Na score (0.678 [0.647-0.709]; P = 0.009). A MELD 3.0 score of 10 could be used as a cut-off point for discriminating high- and low-risk patients. The MELD 3.0 score could stratify patients with Child-Pugh grade A (log-rank P = 0.005) and B (log-rank P < 0.001). Child-Pugh score could stratify patients defined as low risk by MELD 3.0 score (log-rank P = 0.010). Conclusions: The MELD 3.0 score was significantly superior to the MELD and MELD-Na scores in predicting mortality in patients with cirrhosis after TIPS creation.
Nutritional, Lipid Metabolic and Body Composition Features of Children with Spinal Muscular Atrophy
Authors: Feng Yijie , Yao Mei , Xia Yu , Wei Jia , Hong Yi , Long Qi , Chen Fei , Jin Jianing , Zhou Dongming , Hu Jingjing , Cui Yiqin , Chen Xiao , Yuan Changzheng , Mao Shanshan
Published: November 2021

Background
Spinal Muscular Atrophy (SMA) is a progressive neuromuscular disease affecting multiple organs and systems, including nutritional and metabolic status. There is still a lack of relevant large sample size research. We aimed to investigate the nutritional status, serum lipid profile, and body composition characteristics in children with SMA.
Methods
A hospital-based, case-control study was conducted on 91 children with SMA (17.6% of type I, 48.4% of type II, 34.1% of type III) and 91 age- and gender-matched healthy children in a single hospitalized center in China. Anthropometric information, serum lipids parameters and body composition (in subgroup of patients older than 3 years) were collected. According to the anthropometric Z scores, nutritional status was categorized into normal and malnutrition (including under- and over-nutrition) groups.
Results
The prevalence of malnutrition and dyslipidemia in children with SMA was higher than that of controls (49.45% vs. 23.08% and 56.04% vs. 34.07%, respectively and p<0.01). Particularly, the prevalence of lower-than-normal levels of high density lipoprotein (HDL) and apolipoprotein A1 (Apo A1) were significantly higher than that in healthy controls in children with SMA (26.37% vs. 7.69% and 41.76% vs. 6.59%, respectively and p<0.01). In terms of the body composition characteristics in children with SMA II & III, on average, the total body fat mass percentage (FM%) was 43.38% (36.99%, 48.20%), the fat mass index (FMI) was 7.30 (5.07, 8.72), the lean body mass index (LBMI) was 7.70 (6.96, 9.02) and the bone mineral density-z score (BMD-z) was -1.40 (-2.80, -0.60), generally different from the reference profiles in published literature.
Conclusion
Children with SMA in China have obvious nutritional imbalances, abnormal levels of serum lipid and unbalanced body composition. Further research is warranted to explore the potential mechanisms and health management strategies on nutritional and metabolic disorders of SMA.
Dual One-Way Study of Sepsis Survivability Study in Rats Exposed to Cecal Ligation and Puncture with Propofol or Isoflurane
Authors: Ikeda Keita , Osuru Hari Prasad , Thiele Robert H.
Published: November 2021

The authors have requested that this preprint be removed from Research Square.
A randomized controlled study comparing microsurgical clipping via the keyhole approach, conventional craniotomy, and endovascular coiling for ruptured anterior circulation aneurysms
Authors: Zhu Qing , Lan Qing , Chen Ailin
Published: November 2021

Objective: Few prospective randomized controlled studies have investigated the efficacy of endovascular treatment and microsurgical clipping of intracranial aneurysms, especially via microsurgical keyhole approach. We compared the efficacy of three techniques in treating patients with ruptured anterior circulation aneurysms to provide surgeons with a more objective basis for treatment selection. Methods: 150 patients with ruptured anterior circulation aneurysms were randomly assigned to endovascular treatment, conventional craniotomy, and keyhole approach groups. Aneurysm occlusion, surgical time, hospitalization time, hospitalization expenses, and surgical complications were compared between groups. Results: The complete occlusion rates of aneurysms at discharge were 90% in the endovascular group, 94% in the conventional group, and 96% in the keyhole group. No significant differences in complete occlusion rates or Glasgow Outcome Scale scores were found between groups. In the keyhole approach, conventional craniotomy, and endovascular groups, the overall surgical times were 161.78±34.51 min, 201.55±38.79 min, and 85.86±58.57 min, respectively; the hospitalization times were 11.42±6.64 d, 18.03±7.14 d, and 10.57±8.67 d; hospitalization expenses were 10574.25±4154.25 USD, 13214.54±5487.65 USD, and 20134.58±6587.61 USD; and the incidence rates of postoperative complications such as intracranial infection, cerebral vasospasm, hydrocephalus, intracranial hematoma, and epilepsy were 8%, 28%, and 20%. Conclusions: Endovascular coiling and the microsurgical keyhole approach have the advantages of simple execution, time savings, and short hospitalization. Microsurgical clipping of intracranial aneurysms needs to be updated to a minimally invasive procedure to maintain its complementary value with endovascular treatment.Clinical trial registration: The study has been retrospectively registered in clinicaltrial.org (NCT05049564) in Sep. 8th, 2021.
Musculoskeletal Diseases in Marfan Syndrome – A Nationwide Registry Study.
Authors: H.Andersen Niels , Hauge Ellen-Margrethe , Baad-Hansen Thomas , Groth Kristian A. , Berglund Agnethe , Gravholt Claus H. , Stochholm Kirstine
Published: November 2021

BackgroundMarfan syndrome is associated with abnormalities in the musculoskeletal system including scoliosis, pectus deformities, protrusio acetabuli, and foot deformities. Over a life span, many patients with Marfan syndrome will need treatment; however, the musculoskeletal morbidity over a life span is not well described. The aim of the present study was to assess the overall burden of musculoskeletal disease in patients with Marfan syndrome.Materials and MethodsA registry-based, nationwide epidemiological study of patients with a Ghent II verified Marfan syndrome diagnosis from 1977-2014. Each patient was matched on age, and sex with up to 100 controls from the background population.ResultsWe identified 407 patients with Marfan syndrome and 40,700 controls and compared their musculoskeletal diagnoses and surgical treatments using Cox proportional hazards regression (HR). The risk of a registration of a musculoskeletal diagnosis in patients with Marfan syndrome was significantly increased compared to controls (HR: 1.94 (1.69-2.24). One out of six with Marfan syndrome was registered with scoliosis (HR: 36.7 (27.5-48.9). Scoliosis was more common in women with Marfan syndrome compared to men (HR: 4.30 (1.73-1.08)). One out of 11 were registered with a pectus deformity HR: 40.8 (28.1-59.3), and one out of three with a deformity of the foot (HR: 1.9 (1.6-2.3)). The proportion of patients with Marfan syndrome (94/407) that underwent musculoskeletal surgery was also significantly higher (HR: 1.76 (1.43-2.16)). The major areas of surgery were the spine, pectus correction, and surgery of the foot/ancle. Ten patients with Marfan syndrome had elective orthopedic surgery without being recognized and diagnosed with Marfan syndrome until later in life. None of these had scoliosis, pectus deformity or a foot deformity.Among patients with an aortic dissection, the age at dissection was 34.3 years in those with at least one major musculoskeletal abnormality. In patients without a major abnormality the age at dissection was 45.1 years (p<0.01).ConclusionsThe extend of musculoskeletal disease is quite significant in Marfan syndrome and many will need corrective surgery during their life span. Surgeons should be aware of undiagnosed patients with Marfan syndrome when treating patients with a Marfan syndrome like-phenotype.
The Restrictive Type, Infectious Complications, a Long Duration of Illness Might Predict Nadir Hematological Values Among Individuals With Anorexia Nervosa During the Refeeding Period: A Retrospective Study
Authors: Funayama Michitaka , Koreki Akihiro , Mimura Yu , Takata Taketo , Ogino Satoyuki , Kurose Shin , Shimizu Yusuke , Kudo Shun
Published: November 2021

BackgroundAlthough hematological abnormalities in patients with anorexia nervosa have been documented, the mechanisms involved have not been fully clarified, especially during the refeeding period, when hematological values further decrease after admission prior to improving. Here we address potential mechanisms underlying the hematological abnormalities of anorexic inpatients during the refeeding period.MethodsWe recruited patients from 101 admissions corresponding to 55 individual patients with anorexia nervosa with severe malnutrition (body mass index, 13.4 ± 3.4) from the neuropsychiatry unit in Ashikaga Red Cross Hospital during the period from October 1999 to March 2018. We analyzed three hematological cell measures (hemoglobin, white blood cells, platelets) to determine their levels at admission and their lowest levels during the refeeding period and calculated the rate of decrease in those values from admission to the nadir levels. We analyzed each measure using a general mixed model with explanatory variables, including data upon admission and a treatment-related indicator. ResultsThe initial hemoglobin value of 12.1 ± 2.7 g/dl decreased by 22.3% to 9.4 ± 2.5 g/dl; the initial white cell count was 5387 ± 3474/μl, which decreased by 33.6% to 3576 ± 1440/μl; the initial platelet count of 22.6 ± 10.1 ×104/μl decreased by 24.3% to 17.1 ± 8.0 ×104/μl. All nadir levels were observed during the refeeding period from the fifth to tenth day of hospitalization. The anorexia nervosa restrictive type was associated with a lower nadir level of hemoglobin and white blood cell count. Infectious complications were related to a lower nadir level of hemoglobin and platelet count. A longer duration of illness was associated with a lower nadir white blood cell count. Conclusions﻿Nadir hematological cell measures of inpatients with anorexia nervosa during the refeeding period might be predicted by the restrictive type, infectious complications, and a long duration of illness. These factors might be used as indicators to guide clinical approaches for controlling hematological deficiencies during the refeeding period.
Total Hip Arthroplasty After Failed Less Invasive Hip Preservation Surgery for Osteonecrosis of the Femoral Head: A Systematic Review and Meta-analysis
Authors: mo liang , Li Jianxiong , Wang Zhangzheng , Huang Fayi , Xin Pengfei , Ma Chao , Zhang Jiahao , Huang Haoran , Zhou Chi , Liu Yuhao , He Wei
Published: November 2021

BackgroundLess invasive hip-preserving surgery (LIHP) is an effective treatment in delaying total hip arthroplasty (THA) for young patients with osteonecrosis of the femoral head (ONFH). But the success rate of it was not as effective as expected and were significantly reduced with the advancement of the diseases stages. Therefore, it is essential to analysis the impact of LIHP on subsequent THA.MethodsThe search language was restricted to Chinese and English, and the references of included studies were also searched. Chinese databases including CNKI, Wan-Fang databases and VIP, and English databases including PubMed, Embase and Cochrane library were searched by the computer from the inception of each database to 23rd May 2021. The outcome indicators were extracted from the included literature and analyzed by Cochrane Collaboration Review Manager software (RevMan version 5.4). The quality of the studies was scored using the Newcastle-Ottawa scale (NOS).ResultsA total of nine articles met the inclusion and were included in this meta-analysis, two of them were published in Chinese and the remaining studies were published in English. Results showed that the LIHP group has longer operative time (SMD=17.31, 95%CI=6.29 to 28.32, p=0.002), more intraoperative blood loss (SMD=79.90, 95%CI=13.92 to 145.87, p=0.02) and higher rate of varus or valgus femoral stem (OR=4.17, 95%CI=1.18 to 14.71, p=0.03) compared to primary THA group. The risk of intraoperative fracture was higher in the prior LIHP THA group compared with primary THA group but the difference was not statistically significant (OR=5.88, 95%CI=0.93 to 37.05, p=0.06). While there was no significant difference in cup anteversion angle (SMD=-0.10, 95%CI=-0.61 to 0.41, p=0.70), cup inclination angle (SMD=0.58, 95%CI=-0.05 to 1.22, p=0.07), postoperative Harris Hip Score (HHS) (SMD=-0.01, 95%CI=-0.43 to 0.46, p=0.96) and survivorship (OR=1.38, 95%CI=0.34 to 5.55, p=0.65) between THA groups with and without prior LIHP.ConclusionAlthough the prior LIHP increased the difficulty of the conversion to THA with longer operative time, more intraoperative blood loss, and higher rate of intraoperative fracture, it does not detrimentally affect the clinical results of subsequent THA in the mid-term following-up.
NPGREAT: Assembly of the human subtelomere regions with the use of ultralong Nanopore reads and Linked-Reads
Authors: Adam Eleni , Ranjan Desh , Riethman Harold
Published: November 2021

Background

Human subtelomeric DNA regulates the length and stability of adjacent telomeres that are critical for cellular function, and contains many gene/pseudogene families. Large evolutionarily recent segmental duplications and associated structural variation in human subtelomeres has made complete sequencing and assembly of these regions difficult to impossible for many loci, complicating or precluding a wide range of genetic analyses to investigate their function.
Results

We present a hybrid assembly method, NanoPore Guided REgional Assembly Tool (NPGREAT), which combines Linked-Read data with ultralong nanopore reads spanning subtelomeric segmental duplications to potentially overcome these difficulties. Linked-Read sets identified by matches with 1-copy subtelomere sequence adjacent to segmental duplications are assembled and extended into the segmental duplication regions using Regional Extension of Assemblies using Linked-Reads (REXTAL). Telomere-containing ultralong nanopore reads are then used to provide contiguity and correct orientation for matching REXTAL sequence contigs as well as identification/correction of any misassemblies (associated primarily with tandem repeats). While we focus on subtelomeres, the method is generally applicable to assembly of segmental duplications and other complex genome regions. Our method was tested for a subset of representative subtelomeres with ultralong nanopore read coverage in GM12878. 10X Linked-Read datasets with high depth of coverage and a TELL-seq Linked-Read dataset with lower depth of coverage were each combined with the ultralong nanopore reads from the same genome to provide improved assemblies. Tandem repeat regions of the short-read assemblies, which are especially prone to misassembly due to collapse of matching tandemly repeated reads, were readily identified and properly sized by comparison with the nanopore reads.
Conclusion

The NPGREAT method resulted in extension of high-quality assemblies into otherwise inaccessible segmental duplication regions near telomeres, enhancing our ability to accurately assemble human subtelomere DNA. This information will enable improved analyses of the structure, function, and evolution of these key regions.