bluuebunny/crossref_metadata_2025 huggingface dataset:
A Genome-Wide Association Study Identifying SVEP1 Variant as a Predictor of Response to Tolvaptan for Cirrhotic Ascites
Authors: Tanaka Yasuhito , Kawaratani Hideto , Sawai Hiromi , Onishi Masaya , Kogiso Tomomi , Shimada Noritomo , Uojima Haruki , Nakajima Tomoaki , Matsumoto Naoki , Ikejima Kenichi , Ishikawa Toru , Terai Shuji , Motoyama Hiroyuki , Komori Atsumasa , Hirashima Noboru , Saito Satoru , Eguchi Yuichiro , Nojima Masanori , Kawai Yosuke , Tateyama Masakuni , Yoshiji Hitoshi
Published: April 2021

Background and Aims: Tolvaptan, an orally active vasopressin V2-receptor antagonist, has been used for patients with difficult-to-treat ascites in Japan. In this study, we conducted a genome-wide association study (GWAS) in the Japanese population to identify genetic variants associated with tolvaptan’s efficacy for patients with hepatic ascites. Methods: From 2014 through 2018, genomic DNA samples were obtained from 550 patients who were treated with tolvaptan. Of those, 80 cases (non-responder; increase of body weight [BW]) and 333 controls (responder; > 1.5 kg decrease of BW) were included in the GWAS and replication study. Results: GWAS showed 5 candidate SNPs around the miR818, KIAA1109, and SVEP1 genes. After validation and performing a replication study, an SNP (rs2991364) located in the SVEP1 gene was found to have a significant genome-wide association (OR = 3.55, P = 2.01 x 10− 8). Univariate and multivariate analyses showed that blood urea nitrogen (BUN) and SVEP1 SNP were significantly associated with the response (OR = 1.03, p = 0.02 and OR = 4.24, p < 0.0001, respectively). Based on a prediction model of logistic regression analysis in a population with the rs2991364 risk allele, the failure probability (= exp (score: 22.234 + BUN*0.077 + Na*-0.179) (1 + exp (score)) was determined for the detection of non-responders. Assuming a cutoff of failure probability at 38.6%, sensitivity was 84.4%, specificity was 70% and AUC was 0.774. Conclusion: SVEP1 rs2991364 was identified as the specific SNP for the tolvaptan response. The prediction score can identify tolvaptan non-responders and help to avoid a lengthy period of futile treatment.
Benefits of a standardized protocol for axillary management after neoadjuvant chemotherapy in a single center.
Authors: Canal Marina de Paula , Rocha Caroline gomes de almeida , Osório Cynthia Ap. Bueno de Toledo , Bitencourt Almir , Sonagli Marina , Tavares Monique Celeste , Sanches Solange Moraes , Makdissi Fabiana Baroni Alves
Published: April 2021

Purpose: Axillary lymph node status is one of the most important prognostic factors in breast cancer. Neoadjuvant chemotherapy (NACT) has been indicated for locally advanced tumors, and for HER2-positive and triple negative tumors larger than 2.0 and 1.0 cm, respectively, regardless of axillary status. NACT allows clinicians to assess the biological responses of the tumor, predicting prognosis and permitting more conservative surgeries in breast and axilla.Objective: evaluate the use of a standardized protocol after NACT to enable, sentinel node dissection (SLND) in patients with axillary downstaging, avoiding axillary dissection (ALND).Methods: retrospective cohort study of data collected from medical records of patients who underwent NACT in a single center, from January 2014 to December 2018. 471 patients were included in this study: 303 patients before and 165 patients after the implementation of this protocol. This protocol comprises a placement of a metal clip in biopsied lymph node, in patients with up to 2 clinically lymph nodes. After NACT, if a radiologic complete response were achieved, SLND was performed using blue die and tecnecion99. ALDN were avoided in patients whose clipped sentinel node were negative for metastasis. Trial registration number 2786/19, october,19, 2019, retrospectively registered.Results: Protocol avoided ALDN in 18% of selected patients (p< 0.05). Also, patients with triple negative and HER2 positive tumors underwent SLND most frequently, when compared to Luminal tumors (p 0.03).This results showed that the proposed protocol can improve SLND in selected patients when axillary targeted dissection cannot be performed.
What Is the Doppler Profile of the Ophthalmic and the Middle Cerebral Arteries in Male and Female Smokers? A Sex-specific Approach
Authors: Paes Maria Marta Bini Martins , Diniz Angélica Lemos Debs , Martins Luísa Macedo Mendes
Published: April 2021

Vascular dysfunctions can progress and lead to stroke and cardiovascular disease, especially in smokers. The presence of particular vascular changes according to sex has been described and they can be identified by the Doppler method. This study evaluated Doppler velocimetry parameters of the ophthalmic artery (OA) and the middle cerebral artery (MCA) according to sex in smokers regarding a non-smoker group. This cross-sectional observational study included 178 subjects: 93 women and 85 men. Doppler parameters were assessed in OA and MCA. Student’s t-test was used, with p < 0.05. There were no significant differences in OA and MCA Doppler velocimetry data between male non-smokers and smokers. However, female smokers presented several differences compared with non-smokers: lower pulsatility index (PI) and higher peak ratio and second peak of systolic velocity in OA, and higher PI and resistance index and lower end diastolic velocity in MCA. There were different brain vascular waveforms in the group of female smokers compared with non-smokers. Cigarette smoking also led to opposite arterial patterns in OA and MCA in the female group, with signs of falling impedance in OA and increased impedance in MCA. An individualised approach regarding arterial changes according to sex is desirable.
Lipid Droplets Degradation by Autophagy Connects Mitochondria Metabolism to PROX1-driven Expression of Lymphatic Genes and Lymphangiogenesis
Authors: Mece Odeta , Houbaert Diede , Durré Tania , Maes Hannelore , Schaaf Marco , More Sanket , Ganne Maarten , García-Caballero Melissa , Borri Mila , Verhoeven Jelle , Blacher Silvia , Ghesquière Bart , Dewerchin Mieke , Swinnen Johannes , Vinckier Stefan , Soengas Maria , Carmeliet Peter , Noel Agnès , Agostinis Patrizia
Published: April 2021

Autophagy has an emerging vasculoprotective role but whether and how it regulates lymphatic endothelial cells (LEC) and lymphangiogenesis is unknown. Here, we show that genetic deficiency of autophagy in LEC impairs the responses to VEGF-C and injury-driven corneal lymphangiogenesis. Loss of autophagy compromises expression of lymphatic markers, affects mitochondrial dynamics and causes an accumulation of lipid droplets (LDs) in LEC and lymphatic vessels in vivo. When LDs accumulate because lipophagy is impaired, mitochondrial ATP production, fatty acid oxidation (FAO), acetyl-CoA/CoA ratio and expression of lymphangiogenic PROX1 target genes are dwindled. Enforcing mitochondria fusion by silencing dynamin-related-protein 1 (DRP1) in autophagy-deficient LEC fails to affect LDs turnover and lymphatic gene expression, whereas supplementing the acetyl-CoA precursor acetate rescues LEC identity and lymphangiogenesis in LEC-Atg5-/- mice. Our findings reveal that lipophagy in LEC by supporting FAO, preserves a mitochondrial-PROX1 gene expression circuit that ensures LEC identity, responsiveness to lymphangiogenic mediators and lymphangiogenesis.
Clinical Value of CTR, CEA, Histological Type, Ki-67 and EGFR in Predicting pN in Clinical Stage IA Lung Adenocarcinoma and Nomogram Construction
Authors: Yi tengfei , Li Shuo , Qin Kun , Song Guisong , Shao Shengteng , Dai Dongdong , Liu Yuhong
Published: April 2021

To investigate the clinical value of CTR, CEA, histological type, Ki-67 and EGFR in detecting pathological lymph node metastasis (pN) in clinical stage IA (cIA) lung adenocarcinoma and to construct a pN Nomogram model. A total of 374 cIA lung adenocarcinoma patients who had undergone thoracoscopic radical resection with Systematic mediastinal lymph node dissection (SMLD) in the Department of Thoracic Surgery of the Affiliated Hospital of Qingdao University between January 2018 to January 2020 were retrospectively reviewed. The patients were divided into pN(+) and pN(-) groups. Univariate and multivariate Logistic regression analyses were used to analyze the independent risk factors of pN in lung cancer patients. The ROC curve was used to compare the accuracy of CTR, CEA and Ki-67 in predicting pN. R software was used to construct a Nomogram prediction model based on multivariate Logistic regression analysis of the pN risk. The C-index was calculated, and a calibration curve was drawn to judge the calibration degree of the model. The preoperative and intraoperative examinations showed that CTR (OR 570.406, P＜0.001), CEA (OR 1.239, P＜0.001) and micropapillary adenocarcinoma (OR 86.712, P＜0.001) were independent risk factors of pN. Immunohistochemical analysis and gene detection showed that Ki-67 index (OR 4.832, P＜0.001) and EGFR mutations, such as exon 19 (OR 10.319, P＜0.001), exon 21 (OR 7.163, P＜0.001) and exon 19+20 mutations (OR 570.406, P＜0.001), were significant factors in predicting pN. CTR, CEA, histological type, Ki-67 index, and EGFR mutations are the predictive factors of pN in cT1a-3aN0M0 lung adenocarcinoma patients. SMLD is recommended to improve patients’ postoperative survival rate when preoperative CTR≥0.775, CEA＞2.52μg/L or intraoperative rapid freezing pathology shows micropapillary components.
Potential Military Cotton Textiles by Carbon Quantum Dots
Authors: Emam Hossam E. , El-Shahat Mahmoud , Hasanin Mohamed S. , Ahmed Hanan B.
Published: April 2021

Owing to the sensitivity for color vicissitude by exposing to UV irradiation, manufacturing of fluorescent fabrics is widely demanded to be exploited in camping, sensing and military purposes. Pyrimidine based heterocycles were investigated with excellent pharmacological activity, however, their photoluminescence activity was never been investigated till now. The presented approach demonstrate a quite novel route for manufacturing of potential military textiles (fluorescent/UV-protective cotton fabrics with micobicide activity) via exploitation of carbon quantum dots (CQDs) nucleated from pyrimidine based heterocycle (4-(2,4-dichlorophenyl)-6-oxo-2-thioxohexahydropyrimidine-5-carbonitrile, Target Molecule, TM). The synthesized TM & CQDs were separately immobilized within both of native and cationized cotton fabrics to obtain TM@cotton, CQDs@cotton, TM@Q-cotton and CQDs@Q-cotton fabrics. The estimated yellowness index, intensity of the fluorescence peak, UV-blocking activity and microbicide action, were all followed the order of CQDs@Q-cotton > TM@Q-cotton > CQDs@cotton > TM @cotton. CQDs@Q-cotton showed quite good durability, as after 5 washings, yellowness index was diminished from 26.5 to only 20.3, florescence intensity for CQDs@Q-cotton was decreased from 540 nm to 340 nm and transmission percent was increased from 7 % to 10 %. Moreover, even after 10 washings, microbial inhibition (as a percent) against E. coli, Staphylococcus aureus and Candida albicans was estimated to 63 %, 68 % and 67 %, respectively, while, UV protection factor (UPF) was diminished from 38.2 (very good) to 21.5 (good). The presented unique route was succeeded for manufacturing of durable fluorescent textiles that could be superiorly applied as potential military textiles.
Kinetic Modeling of Enzymatic Hydrolysis of Cellulosic Material
Authors: Shokrkar Hanieh , Ebrahimi Sirous
Published: April 2021

Development of a kinetic model for analysis of processes for fermentable sugars production is a significant challenging issue due to the complexity of the enzymatic hydrolysis of cellulose. This paper presents a useful mathematical model for simulation and evaluation of enzymatic hydrolysis of cellulosic material. The simulation results were compared with a set of experimental results reported in the literature, in order to validate the proposed model. A comparison was also made between the proposed model and another model previously described in the literature Numerical results indicate that the proposed model gives a more accurate prediction of time course production of glucose, cellobiose, and cellulose during enzymatic hydrolysis cellulosic materials.
An isolation system to collect high quality and purify extracellular vesicles from serum
Authors: Yang Jian , Liao Li , Gao Xin , Xing Xiaotao , Huang Haisen , Tang Qi , Ma Shixing , Xu Xun , Liang Cheng , Li Maojiao , Tian Weidong
Published: April 2021

Background: Extracellular vesicles (EVs) are membrane encapsulated nanoparticles that function as carriers and play a role in intercellular communication. There are a large number of EVs in the blood and serve as an indicator of pathophysiological conditions. Studies on the basics and application of EVs are hampered by the limitations of current protocols to isolate EVs from blood. However, current isolation methods are difficult to achieve a balance between yield and purity.Results: Firstly, we use Sepharose-4B to build a self-made size exclusion chromatography (SEC) column and perform separation and identification. Then we use the SEC column to systematically compare the efficiency with the most common EV isolation methods: ultracentrifugation (UC) and total exosomes isolation commercial kit (TEI). The EVs isolated through different methods were characterized the yield and size of EVs, analyzed their protein profiles, the morphology and purity were observed under the transmission electron microscope. To further improve the quality and purity, we combined SEC and UC methods and established a two-steps method to isolated EVs from serum.Conclusion: Our study presents the combination of size-exclusion chromatography and ultracentrifugation as a feasible and time-saving method to isolate high quality and purity extracellular vesicles from serum.
Analgesic effect of lidocaine in paracervical block in women undergoing colposcopy and cervical biopsy: a randomized clinical trial
Authors: Nokhostin Fahimeh , Behdad Shekoufeh , Mousavi-Roknabadi Reyhaneh Sadat , Mousavi-Roknabadi Razieh Sadat
Published: April 2021

Objective: To investigate the effect of lidocaine in paracervical block in women undergoing colposcopy and cervical biopsy.Methods: This a triple-blind randomized controlled trial (July-September 2020) was conducted on women who were candidate for the colposcopy and cervical biopsy with American Society of Anesthesiologists classification Class I or II. They were randomly allocated to receive a single dose of lidocaine hydrochloride 2% or injectable sodium chloride 0.9% paracervical block, and then, cervical biopsy was done. The pain score was asked and intra-procedural and 5-minutes post-procedural in both groups, using the VAS tool. Also, patients' satisfaction after the procedure and complications were recorded.Results: Totally, 74 patients (37 in each groups) were enrolled, with the mean±SD age of 35.91±8.10 years. The mean±SD of pain score intra-procedural was statistically higher in patients in the treatment group (0.92±1.53 vs. 2.73±2.34, P<0.001), as well the pain score 5-minutes post-procedural (0.27±0.65 vs. 0.95±1.15, P=0.003). Also, the mean±SD of patients' satisfaction score was higher in the treatment group (4.65±0.82 vs. 4.05±1.41, P=0.03). Dizziness were observed only in the treatment group, statistically (P<0.001).Conclusion: Paracervical block using lidocaine could reduce the intra-procedural and 5-minutes post-procedural pain. Also, it can increase the patients' satisfaction with the procedure.
Heat-induced magnetic transition accelerates redox couple mediated electrocatalytic water oxidation in alkaline media
Authors: Liu Duanduan , Lu Mengfei , Liu Depei , Yan Shicheng , Zhou Wei , Zhang Lunyong , Zou Zhigang
Published: April 2021

The redox couple oxidation as an initial step for oxygen evolution reaction (OER) may be key for high electricity consumption in electrochemical redox couple mediated water splitting. Here, we report a heat-induced magnetic transition strategy to speed up the oxidation kinetics of redox couples. The activation energy of Ni2+/Ni3+ redox couple oxidation was significantly decreased by heating the Ni0.5Fe0.5OxHy OER catalyst above Néel temperature (TN) of 70oC. In such a strategy, the heat in stead of electricity to overcome the spin flipping of Ni2+/Ni3+ oxidation through the heat-sensitive ferrimagnetic-to-paramagnetic spin state changes. The efficient heat-electricity coupling enables Ni0.5Fe0.5OxHy to produce the lowest OER overpotential of 170 mV at 100 mA cm-2 at 90 oC in alkaline electrolyte, outperforming the benchmark IrO2 catalyst. Our findings demonstrate the application potential of heat-sensitive magnetic materials in the field of electrocatalysis, which may inspire insights into designing of multi-energy complementary OER devices.
Dynamic Analysis of Ocular Fundus Changes after Different Doses of Bevacizumab in the Treatment of Retinopathy of Prematurity in Threshold Period
Authors: Chen Feng , Yu Ying , Wang Jianxun , Liu Tian , Xiang Daoman
Published: April 2021

Purpose: To analyze the efficacy of three different doses of bevacizumab treatment on Threshold retinopathy of prematurity during different periods . Methods: 36 cases (72 eyes) of infants with threshold ROP were analyzed, whom were treated with intravitreal injection of 1.25mg, 0.75mg or 0.5mg bevacizumab respectively from October 1st, 2016 to September 30th, 2017. After treatment, fundus examination results during five time points were recorded and classified into four grades according to the efficacy. Results: There were significant differences in the changes of fundus among the 3 groups on the 4th day and the 2nd week after treatment （P<0.001）. In the 1.25mg group, there was a significant difference in the changes of fundus on the 4th day after treatment VS. the 2nd week after treatment (P<0.001). In the 0.5mg and 0.75mg group respectively, the changes of fundus were significantly different between each consecutive time points of the 4th day, 2nd week, 4th week and 2nd month after treatment (P<0.001,P<0.001,P=0.01; P<0.001,P=0.01,P=0.032). The proportion of normal retinal vessels of the three groups is 41.67% - 66. 67% in the 3rd month after treatment.Conclusion: Among the three doses of bevacizumab treatment, the efficacy of 1.25mg group is the best on the 4th day and the 2nd week after treatment, and there was no difference after 4 weeks. The efficacy of 0.5mg and 0.75mg group changed significantly from the 4th day to the 2nd month after treatment. Long-term follow-up of fundus changes was still needed to avoid recurrence of ROP whatever the dose of bevacizumab was uesed.
Investigating a Newly Developed Educational Orthopedic Application for Medical Interns
Authors: Daliri Mahla , Majd Hassan M. , Moradi Ali
Published: April 2021

BackgroundIn COVID 19 era, the literature on e-learning- or particularly smartphone (m-learning)- has considerably increased its attention on the subject of medical knowledge transfer. Regarding the importance of the orthopedic knowledge for general practitioners and the inadequacy of the orthopedics internship duration in Mashhad University of Medical Sciences (MUMS), we have developed and investigated a smartphone orthopedic educational application, named “Orthobox”.MethodsIn a quasi-clinical before-after trial study, we investigated the application benefits for medical interns attending MUMS orthopedic departments. A total of 120 students (64 and 56 students in control and case groups respectively) were recruited. The application consists of five main parts of medication, common order samples, common prescriptions, cast and splint types, and educational movies. Students who passed the course without getting access to the application (control group) and students who were using application during the course (case group) were defined, and comparison was done between them objectively-through final exam score comparison and subjectively-through Visual Analogue Scale (VAS) questionnaire score comparison. Besides, using case group students’ activity report provided by the application panel, correlational analysis was done on their amount of activity on each of the main parts of the application and the corresponding question exam and VAS score separately.ResultsThe case group of the study generally achieved higher final exam scores, mainly on Order question score (P value<0.001). Total VAS scores were also greater in case group (P value =0.001). It has also been identified that there is a notable positive trend between student’s amount of usage of the application and their final exam scores through correlational analysis. This correlation was not significant about students’ application visit numbers and VAS scores. ConclusionThese results on one hand, suggest that m-learning has got the potential to improve students’ medical knowledge and skills by organizing must-to-learn content specified for intern students of orthopedics and on the other hand, cause students more satisfied by their education.Level of evidence: Level III (Evidence obtained from well-designed controlled trials without randomization (i.e. quasi-experimental).
Nitrogen availability controls plant carbon storage with warming
Authors: Zhou Guiyao , Terrer César , Hungate Bruce , Gestel Natasja van , Zhou Xuhui , Groenigen Kees Jan van
Published: April 2021

Plants may slow global warming through enhanced growth, thereby stimulating the land carbon (C) sink. However, the key drivers determining responses of plants to warming remain unclear, causing uncertainty in climate projections. Using meta-analysis, we show that the effect of experimental warming on plant biomass is best explained by soil C:N ratio, an indicator of soil nitrogen (N) availability. Our results suggest that warming stimulates plant C storage most strongly in ecosystems where N limits plant growth, and may inform model predictions of warming may improve by considering spatially explicitly .
The Magnitude and Drug Resistance Profile of Extended Spectrum Β-Lactamase (Esbl) Producing Gram-Negative Bacteria from Different Inanimate Objects at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia
Authors: Jemberu Asegedech Asmamaw , Tullu Kassu Desta , Mulate Yimtubeznash Woldeamanuel
Published: April 2021

Background: Infections caused by gram-negative bacteria are causing morbidity and mortality worldwide. The production of extended-spectrum β-lactamases (ESBLs) is an important mechanism that is responsible for resistance to the third-generation cephalosporin. The purpose of this study was to determine the magnitude and drug resistance profile of ESBL producing gram-negative bacteria isolated from various inanimate objects at Tikur Anbessa Specialized Hospital. Methods: Laboratory based cross-sectional study was conducted involving a total of 216 isolates from January to March 2019. The samples were taken from different inanimate objects at Tikur Anbessa Specialized Hospital using pre-moistened sterile swabs. Screening of ESBLs was done using ESBL CHROME agar and confirmed with combined disk diffusion test. Antimicrobial susceptibility testing was done by disc diffusion method. The data were analyzed using SPSS software version 20 and descriptive statistical tests were performed. Results: 33/216 (15.3%) isolates were found to be ESBL producers based on the confirmatory test (combined disk method). Different ESBL producing gram-negative bacteria were isolated from the various inanimate objects of TASH including, Klebsiella ozaenae, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella rhinoscleromatis, Citrobacter spp, Escherichia coli, Serriatia spp and Acinetobacter spp. The isolates were found to be 100% resistant to ceftazidime and ceftriaxone. Conclusion: It is worrisome to detect ESBL producing gram-negative bacteria from the inanimate objects of TASH, calling for systematic screening of inanimate objects for ESBL and other multidrug-resistant bacteria in the hospital. Furthermore, strengthening the infection prevention practice is vital to halt the transmission of these microorganisms.
Surface D2 Autoreceptor Expression on Substantia Nigra Dopamine Neuron Dendrites
Authors: Williams John T , Lebowitz Joseph J. , Bunzow James R. , Robinson Brooks , Sesack Susan R.
Published: April 2021

G-Protein coupled D2 receptors expressed on dopamine neurons, i.e. D2-autoreceptors (D2Rs), negatively regulate transmitter release and cell firing in axonal terminals and somatodendritic compartments. However, as the membrane distribution of D2Rs at somatodendritic signaling sites has not been fully characterized, functional mechanistic details remain uncertain. This study utilized a knockin mouse to examine surface D2Rs linked at the N-terminus to a superecliptic pHlourin green fluorescent protein epitope (SEP) in dopamine neurons of the substantia nigra. By incubating live slices with a highly specific anti-SEP antibody, the selective labeling of plasma membrane associated receptors was achieved. The SEP-D2Rs appeared as puncta like structures apposed to the surface of dendrites and soma of dopamine neurons. The percentage of D2R expression apposed to TH positive structures varied linearly with the density of TH fibers observed. TH-associated SEP-D2Rs displayed a cell surface density of 0.180 puncta per µm2, which corresponds to an average frequency of 1 punctum every 1.326 µm using nearest neighbor analysis. The distinct punctate appearance of the anti-SEP staining indicates there is a population of D2Rs organized in discrete clusters along the plasma membrane, an arrangement that can spatially localize signaling and influence GPCR efficacy. The results also indicate that D2Rs are spatially distributed on the plasma membrane at a frequency higher than previously reported.
Effects of Dietary Aspirin Supplementation on Growth Performance, Carcass Characteristics, Gastrointestinal Organs and Liver Enzymes, Abdominal Fats, Immune Response, Cecum Microflora and Fatty Acid Profile in Breast Meat of Broiler Chickens
Authors: Tavakoli Masoomeh , Bouyeh Mehrdad , Seidavi Alireza
Published: April 2021

The authors have requested that this preprint be removed from Research Square.
Mesoporous Polydopamine Nanoparticles Carrying Peptide RL-QN15 Show Potential for Skin Wound Therapy
Authors: Qin Pan , Meng Yi , Wang Ying , Gou Xinyu , Liu Naixin , Yin Saige , Hu Yan , Sun Huiling , Fu Zhe , Wang Yinlei , Li Xiaojie , Tang Jing , Yang Ying , Deng Ziwei , Yang Xinwang
Published: April 2021

Background: Skin wound healing remains a considerable clinical challenge, thus stressing the urgent need for the development of new interventions to promote repair. Recent researches indicate that both peptides and nanoparticles may be potential therapies for the treatment of skin wounds. Methods: In the current study, the mesoporous polydopamine (MPDA) nanoparticles were prepared and the peptide RL-QN15 that was previously identified from amphibian skin secretions and exhibited significant potential as a novel prohealing agent was successfully loaded onto the MPDA nanoparticles, which was confirmed by results of analysis of scanning electron microscopy and fourier transform infrared spectroscopy. The encapsulation efficiency and sustained release rate of RL-QN15 from the nanocomposites were determined. The prohealing potency of nanocomposites were evaluated by full-thickness injured wounds in both mice and swine & burn wounds in mice. Results: Our results indicated that, compared with RL-QN15 alone, the prohealing potency of nanocomposites of MPDA and RL-QN15 in the full-thickness injured wounds and burn wounds in mice was increased by up to 50 times through the slow release of RL-QN15. Moreover, the load on the MPDA obviously increased the prohealing activities of RL-QN15 in full-thickness injured wounds in swine. In addition, the obvious increase in the prohealing potency of nanocomposites of MPDA and RL-QN15 was also proved by the results from histological analysis. Conclusions: Based on our knowledge, this is the first research to report that the load of MPDA nanoparticles could significantly increase the prohealing potency of peptide and hence highlighted the promising potential of MPDA nanoparticles-carrying peptide RL-QN15 for skin wound therapy.
A Comparative Study of Forest Methods for Time-to-Event Data: Variable Selection and Predictive Performance
Authors: Liu Yingxin , Zhou Shiyu , Wei Hongxia , An Shengli
Published: April 2021

BackgroundAs a hot method in machine learning field, the forests approach is an attractive alternative approach to Cox model. Random survival forests (RSF) methodology is the most popular survival forests method, whereas its drawbacks exist such as a selection bias towards covariates with many possible split points. Conditional inference forests (CIF) methodology is known to reduce the selection bias via a two-step split procedure implementing hypothesis tests as it separates the variable selection and splitting, but its computation costs too much time. Random forests with maximally selected rank statistics (MSR-RF) methodology proposed recently seems to be a great improvement on RSF and CIF.MethodsIn this paper we used simulation study and real data application to compare prediction performances and variable selection performances among three survival forests methods, including RSF, CIF and MSR-RF. To evaluate the performance of variable selection, we combined all simulations to calculate the frequency of the correct variables ranking in the top by variable importance measure, where higher frequency means better selection ability. We used Integrated Brier Score (IBS) to measure the prediction accuracy of all three methods. The smaller IBS value, the greater the prediction. Results1. Simulations show that three forests methods differ slightly in prediction performance. Real data results show that three forest methods all have advantages in different scenarios.2. For variable selection performance, 1) MSR-RF and CIF have higher selection frequency than RSF when there are multiple categorical variables in the simulation datasets, and CIF perform well especially with the interaction term.2) Forests methods seem to be suitable for processing data with correlation, as the selection frequency fluctuates slightly when correlation degree changes.3) RSF and MSR-RF outperform CIF with complete binary covariate type. MSR-RF outperform RSF and CIF with complete continuous covariate type.4) MSR-RF perform relatively robust when the variable dimension increases, while CIF perform poorly.Conclusions All three forests methods have respective advantages in different situations. It is important to choose the appropriate method based on the covariates in practice.
Deciphering The Molecular Mechanism Of Water Boiling At Heterogeneous Interfaces
Authors: Karalis Konstantinos , Zahn Dirk , Prasianakis Nikolaos , Niceno Bojan , Churakov Sergey V.
Published: April 2021

Water boiling control evolution of natural geothermal systems is widely exploited in industrial processes due to the unique non-linear thermophysical behavior. Even though the properties of water both in the liquid and gas state have been extensively studied experimentally and by numerical simulations, there is still a fundamental knowledge gap in understanding the mechanism of the heterogeneous nucleate boiling controlling evaporation and condensation. In this study, the molecular mechanism of bubble nucleation at the hydrophilic and hydrophobic solid-water interface was determined by performing unbiased molecular dynamics simulations using the transition path sampling scheme. Analyzing the liquid to vapor transition path, the initiation of small void cavities (vapor bubbles nuclei) and their subsequent merging mechanism, leading to successively growing vacuum domains (vapor phase), has been elucidated. The molecular mechanism and the boiling nucleation sites' location are strongly dependent on the solid surface hydrophobicity and hydrophilicity. Then simulations reveal the impact of the surface functionality on the adsorbed thin water molecules film structuring and the location of high probability nucleation sites. Our findings provide molecular-scale insights into the computational aided design of new novel materials for more efficient heat removal and rationalizing the damage mechanisms.
What Role Conceptions Do Multi-Healthcare Professionals Have of Physicians and What Role Expectation Do They Have of Physicians in a Community?
Authors: Haruta Junji , Goto Ryohei , Ozone Sachiko , Maeno Tetsuhiro
Published: April 2021

Background: To create an effective community-based integrated care system, interprofessional collaboration based on the healthcare professionals’ mutual understanding of their respective roles must be promoted. This study aimed to identify the role conception and role expectation that other healthcare professionals have towards physicians in the context of community-based integrated care system.Methods: We organized focus groups and adopted ‘Role Theory’ as a theoretical framework. We collected data for healthcare professionals attending a conference on community-based integrated care systems in Japan. Fifty-four healthcare professionals other than physicians consented to participating in 7 focus groups. Theme analysis based on the recorded and verbatim transcripts was conducted on collation with the research questions.Results: The role conception of physicians is as a figure of intellectual authority positioned at the top of a traditional hierarchy, with a personal character of criticism/autonomy/closedness, not accommodating any interference from others, and upholding the Biomedical Model as an absolute standard. In response to it, the role expectation of physicians in a community is that they undertake actions that only physicians can undertake to ensure that a flat organization functions properly to provide medical explanations during transitions and to offer healthcare support for patients who are difficult to access. The role expectation also includes a perception of patients as human beings, with physicians adapting to the Bio-Psycho-Social Model, explaining to patients about their disease as an authoritative voice based on an understanding of psychosocial circumstances, and sharing the prognosis of disease or disability. The personal character expected was for someone with an open mind who allows others to seek advice, as well as a sense of approachableness which makes it easier for others to seek advice. Conclusion: In the context of a community-based integrated care system, physicians should consider understanding of the role conception and role expectation that other professionals have of them, and need to endeavor to create an open relationship with all healthcare professionals and give careful thought to their own roles.
APOS - Antibiotic Prophylaxis For Preventing Infectious Complications In Orthognathic Surgery: Study Protocol For A Phase III, Multicentre, Randomised, Controlled, Double Blinded, Clinical Trial With Two Parallel Study Arms
Authors: Ristow Oliver , Hofele Christof , Münch Philipp , Danner Sylvia , Dietzel Anja , Krisam Johannes , Pilz Maximilian , Klose Christina , Hoffmann Jürgen , Freudlsperger Christian
Published: April 2021

Background: It is a constant debate among surgeons whether the use of prolonged postoperative antibiotics may reduce surgical site infection rates. As specific treatment guidelines are still lacking, many surgeons continue to use broad-spectrum antibiotics, causing not only increased costs but also contributing to the potential for antibiotic resistance. Hence, there is an urgent need for an appropriately designed prospective clinical trial, to investigate whether a prophylactic use of antibiotics after surgery actually decreases surgical site infections to a clinically relevant degree.Methods: This study presents a multicentre, randomised, controlled, double-blinded, clinical trial with two parallel study arms to demonstrate that no postoperative antibiotic prophylaxis (AP) is not inferior to antibiotic prophylaxis with respect to surgical site infections in patients having undergone orthognathic surgery. The primary efficacy endpoint is defined as the occurrence of postoperative surgical site infections within 30 days of surgery. Secondary endpoints are further efficacy and subject-oriented parameters within 90 days after surgery. The entire trial is planned for 54 months, with an enrolment of 1420 patients over 39 months by 14 national participating centres. Discussion: As a highly standardised procedure on an exceeding, healthy and young homogenous study population and identical processes all over the world, elective orthognathic surgery as clean-contaminated procedure provides comparable intervention groups with balanced baseline characteristics, comparable surgical duration, even when performed within multiple centres. Therefore, evaluating antibiotic prophylaxis after orthognathic surgery will be of high scientific value representable for other surgical procedures.Trial registration: DRKS - German Clinical Trials Register - DRKS00022838; EudraCT No. 2020-001397-30
Prehospital notification reduced time delays but not neurological outcomes in acute ischemic stroke
Authors: Sangari Azra , Akhoundzadeh Kobra , Vahedian Mostafa
Published: April 2021

Introduction: Since timely thrombolytic therapy is a crucial variable in acute ischemic stroke recovery, health care systems are trying to find new interventions to reduce treatment delay in order to improve neurological function. In Iran, SAMA code as a prehospital notification plan has been developed to help emergent stroke treatment. This study aimed to compare time delay to thrombolysis therapy and neurological outcomes between prehospital notification (SAMA)-transported patients and self-transported patients in acute ischemic stroke.Methods and materials: In this retrospective cohort study, the data of 185 stroke patients treated with intravenous thrombolysis were gathered. There were two groups including, SAMA-transported (n=110) patients and self-transported (n=75) patients. The treatment delays including, onset to needle time (ONT), onset to door time, (ODT), door to CT time (DCT) and door to needle time (DNT) as well the neurological scores measured using NIHSS and mRS were analyzed between two groups. p-value<0.05 was considered as significant.Results: The results showed that delay times reduced in SAMA-transported patient compared to that in self-transported patients. The findings revealed a significant difference in ONT (150 (120-180) vs 180 (150-225) (p=0.001), DNT (80 (60-105) vs 100 (80-125) (p=0.0001), and DCT (27 (20-37) vs 36 (24-52) (p=0.001) between SAMA-transported patients and self-transported patients. The times are represented as minute (median and IQR). However, there was no significant difference between two groups in terms of neurologic deficit severity. Also, there was no relationship between the delay time and neurological outcomes. Conclusion: Although SAMA prehospital notification could partially reduce treatment delay times in acute ischemic stroke, such reduction was not enough to impact on neurologic deficit recovery. It seems more reduction in delay time is needed to significant improvement of neurological dysfunctions.
Septic Shock Caused By Aeromonas Daca: A Bacterium That We Have Neglected In The Past.
Authors: Zhao Qiquan , Zhou Yuguo , Han Xiaoli , Jian Li
Published: April 2021

Introduction: For decades, Aeromonas daca has often been mistaken for Aeromonas hydrophila by phenotypic identification systems and shows obvious characteristics of virulence. To our knowledge, a total of two English-language studies with relatively complete data were retrieved.Case presentation: The patient, a 26-year-old male with no underlying disease, was admitted to our hospital for 3 days because of cough, expectoration and shortness of breath. According to blood and lavage fluid cultures and next-generation sequencing (NGS), the patient was diagnosed with an A. daca infection. He soon deteriorated to a critical condition complicated with septic shock and died after active rescue treatment.Conclusions: A. daca infection is lethal, and an accurate taxonomy can improve our understanding of the epidemiological distribution and virulence potential of this human pathogen. Third-generation cephalosporins and carbapenems should be used cautiously in the treatment of severe A. daca infection, and the best regimen is cefepime or fluoroquinolones.
Automated Detection of Poor-Quality Data: Case Studies in Healthcare
Authors: Dakka M.A. , Nguyen T. , Hall J.M.M. , Diakiw S.M. , VerMilyea M. , Linke R. , Perugini M. , Perugini D.
Published: April 2021

The detection and removal of poor-quality data in a training set is crucial to achieve high-performing AI models. In healthcare, data can be inherently poor-quality due to uncertainty or subjectivity, but as is often the case, the requirement for data privacy restricts AI practitioners from accessing raw training data, meaning manual visual verification of private patient data is not possible. Here we describe a novel method for automated identification of poor-quality data, called Untrainable Data Cleansing. This method is shown to have numerous benefits including protection of private patient data; improvement in AI generalizability; reduction in time, cost, and data needed for training; all while offering a truer reporting of AI performance itself. Additionally, results show that Untrainable Data Cleansing could be useful as a triage tool to identify difficult clinical cases that may warrant in-depth evaluation or additional testing to support a diagnosis.
The transdermal penetration of novel amphiphilic MTC-Y carrier
Authors: Kuropka Piotr , Janeczek Maciej , Bursy Dawid
Published: April 2021

A transdermal drug delivery system capable of transporting the active substance through skin is alternative path for drug delivery for different purposes. In an attempt to demonstrate the permeability of the active substance through the skin layers of the rats, the amphiphilic MTC-Y carrier was combined with fluorochromes of different chemical properties. After extraction, the skin material was subjected histological examination under fluorescence microscope Nikon Eclipse 80i UV-2A filter (EX330-380, DM-400, BA-420). Moreover, histological slides routinely stained with haematoxylin were analysed. Results indicate that use of the MTC-Y carrier seems to be very promising compound for drug delivery both locally and systematically
Molecular Characterization of Two Isolates of Wild Tomato Mosaic Virus and Chilli Veinal Mottle Virus Co-infecting Chilli Pepper in China
Authors: Hu Yongliang , Chen Yuqin , Su Xiaoxia , Huang Jiawei , Yin Hongxing , Ma Guanrun , Wang Yingqing , Zhang Jie , Zhang Zhongkai , Ding Yong , Zheng Kuanyu
Published: April 2021

The present study reports observation of a field chilli pepper disease consisting of a co-infection with two potyviruses: Wild tomato mosaic virus Dehong isolate (WTMV-Dh) and Chili veinal mottle virus Dehong isolate (ChiVMV-Dh). We obtained the complete genome sequences of these two viruses by NGS sequencing. The WTMV-Dh is 9,598 nucleotides (nt) in length and encodes a complete polyprotein of 3,075 amino acids (aa). The polyprotein of WTMV-Dh shares 76.1–82.6% nt and 85.3–89.5% aa identities with the other three WTMV isolates reported previously. The ChiVMV-Dh is 9688 nt in length and encodes a complete polyprotein with 3, 089 aa. The polyprotein of ChiVMV-Dh shares 80.8–92.2% nt and 85.3–95.6% aa identities with the other ChiVMV isolates reported previously. Following phylogenetic analysis based on the polyprotein sequences of other potyviruses, WTMV-Dh clustered with the Vietnam strain WTMV-Laichau while ChiVMV-Dh clustered with several ChiVMV Sichuan isolates. Evaluation of the recombination events within the WTMV and ChiVMV subgroups indicated that some putative recombination events occurred in critical regions. These regions include the N-terminal of HC-Pro and P1 region of WTMV-Dh, CP and the P3 to CI region of ChiVMV-Dh, which may be new evidence of adaptive evolution of potyviruses.
On the order of the non-primes of type 6n+5 and 6n+1
Authors: Wolmersdorfer Christoph
Published: April 2021

The fundamental importance of prime numbers for mathematics is that all other natural numbers can be represented as a unique product of prime numbers[1]. For centuries, mathematicians have been trying to find an order in the occurrence of prime numbers. Since Riemann´s paper on the number of primes under a given size, the distribution of the primes is assumed to be random[2]. Here, I show that prime numbers are not randomly distributed. Their positions are determined by the order of occurrence of the nonprimes of types 6n+5 and 6n+1. By using parametric sine functions, I will show here that all assumptions known today regarding the distribution of prime numbers larger than 3 are wrong. In particular, this refutes Riemann´s hypothesis of random distribution of prime numbers. Furthermore, I will show an exact primality test based on these parametric sine functions, which only uses one parameter.
The Change of Retinal Microvascular, Microstructure and Expression of IL-6, CD18, ICAM, TNF-α and VEGF in The Early Stage of Rat Diabetic Retinopathy
Authors: Xiao Ang , Zhong HuiFeng , Xiong Lei , Yang Lin , Xu YunFang , Shao Yi , Zhou Qiong
Published: April 2021

The authors have requested that this preprint be removed from Research Square.
A New Qualitative RT-PCR Assay Detecting SARS-CoV-2
Authors: Favaro Marco , Mattina Walter , Pistoia Enrico Salvatore , Gaziano Roberta , Francesco Paolo Di , Middleton Simon , D'Angelo Silvia , Altarozzi Tullio , Fontana Carla
Published: April 2021

Purpuse: The world is facing an exceptional pandemic caused by SARS-CoV-2. To allow the diagnosis of COVID infection, several assays based on the real-time PCR technique have been proposed. The requests for diagnosis are such that it was immediately clear that the choice of the most suitable method for each microbiology laboratory had to be based on one hand, the availability of materials, on the other hand, the personnel and training priorities for this activity. Unfortunately, due to high demand, the shortage of commercial diagnostic kits has also become a major problem. To overcome these critical issues, we have developed a new qualitative RT-PCR probe based. Methods: Our system detects three genes: RNA-dependent RNA polymerase (RdRp), envelope (E) and nucleocapsid (N), while the b-actin gene was used as an endogenous internal control. Results: The results of our assay show complete agreement with those obtained using a commercially available kit, except for two samples that did not pass the endogenous internal control. The coincidence rate was 0.96. The LoD of our assay was 140 cp/reaction for N and 14 cp/reaction for RdRp and E. Conclusion: Our kit was designed to be open either for the nucleic acid extraction step or on the RT-PCR assay to be carried out on several instruments. Therefore, it is free from the industrial production logics of closed systems and, conversely, it is hypothetically available for distribution in large quantities in any microbiological laboratory. The kit is currently distributed worldwide (called: MOLgen-COVID-19; Adaltis). A new version of the kit detecting S gene also is coming available.