bluuebunny/crossref_metadata_2025 huggingface dataset:
Deregulation of arachidonic acid metabolism CYP450 pathway is associated with microvascular invasion in hepatocellular carcinoma
Authors: Wang Kai , Shi Jihua , Gao Jie , Sun Yaohui , Wang Zhihui , Shi Xiaoyi , Guo Wenzhi , Jin Yang , Zhang Shuijun
Published: June 2022

The liver is one major organ undergoing arachidonic acid synthesis and metabolism; however, the role of arachidonic acid metabolism in hepatocellular carcinoma (HCC) has not been fully elucidated. In this study, the expression of key arachidonic acid metabolism pathway genes in HCC were determined by bioinformatics analysis of publicly available datasets, proteomics analysis of clinical HCC tissues, and immunohistochemical analysis of tissue microarrays (TMAs) of HCC. By comparing the differential expression of hepatic arachidonic acid metabolic genes, we found that the expression of the cytochrome P450 (CYP450) pathway genes, at both mRNA and protein levels, was significantly decreased in HCC tissues. The deregulation of the arachidonic acid metabolism CYP450 pathway is markedly correlated with the pathological features and prognosis of HCC. In addition, we found a significant correlation between the activity of the CYP450 pathway and vascular invasion status in HCC, indicating it would have potential as a predictive factor for early recurrence in HCC patients.
Deciphering the effects of co-culturing on the metabolite profiles of Ligilactobacillus reuteri ZJ625 and Limosilactobacillus salivarius ZJ614 using untargeted metabolomics
Authors: Kwoji Iliya Dauda , Okpeku Moses , Aiyegoro Olayinka Ayobami , Adeleke Matthew Adekunle
Published: June 2022

Ligilactobacillus reuteri ZJ625 (ZJ625) and Limosilactobacillus salivarius ZJ614 (ZJ614) are important lactic acid bacteria with the potential for use as probiotics. To better understand the mechanisms of cell-to-cell interactions between ZJ625 and ZJ614 and elucidate their probiotics potentials, we studied the effects of co-culturing in defined media on the metabolomes. The strains were cultured singly (L. reuteri ZJ625 or L. salivarius ZJ614) and in co-cultures (L. reuteri ZJ625 plus L. salivarius ZJ614) and harvested at the mid-exponential phase. Single-phase extraction method was used to extract the metabolites from pre-weighed cells for the two-dimensional gas-column time-of-flight-mass spectrometry (GCxGC- TOFMS) analysis. The data was obtained using a Leco corporation ChromaTOF software and exported for statistical, pathway enrichment, and impact analyses using MetaboAnalyst 5.0. Principal component analysis (PCA) indicated an overlap of the samples from the two batches, indicating no significant batch effect. The data was then analyzed using the group allocations. This study revealed 1388 metabolites from L. reuteri ZJ625 and L. salivarius ZJ614 single and co-cultures in defined media, of which 18.87% were significantly expressed (p < 0.05). Of the significantly expressed metabolites, 28% DEMs were identified (p < 0.05, VIP > 1), of which 51.3% were annotated while 48.6% are currently not annotated in the databases. The whole metabolome of the strains in single and co-cultures revealed the expression of several important metabolites, including arabinofuranose, methyl-galactoside, N-acetyl-glutamic acid, phosphoric acid, decanoic acid, metyrosine, and deoxypentafuranose which play roles in different metabolic and biosynthetic pathways, hence confirming the probiotic potential as single- or multi-strain cultures. The co-culturing of the strains influenced the metabolites profiles of the strains showing additive and regulatory differential metabolites expressions. Pathway enrichment and impact analyses revealed the association of the differentially expressed metabolites with functional effects such as antihypertensive, antimicrobial, and microbiome stimulation.
Neuroendocrine involves in flesh quality degradation of Litopenaeus vannamei during waterless transport by disturbing physiological and metabolic response
Authors: Xu Defeng F. , Zheng Xiaoxian , Li Caihong , Sun Lijun , Qin Xiaoming , Wang Yaling
Published: June 2022

The flesh quality degradation of shrimp during waterless transport has been observed and the underlying mechanism remains unknown. The present study aimed to clarify the biochemistry mechanisms of flesh degradation with integration of quality evaluation, metabolic profiling, and histopathological analysis. The flesh quality indicators such as water holding capacity, protein and lipid contents, amino acid composition, and myofiber characteristics degraded with the prolongation of combined stress. In addition, the metabolites including gamma-aminobutyric acid, Val-Ala, Trh and derivatives of carnitine, phosphocholine, and prostaglandin all reduced significantly under combined stress (P < 0.05). Furthermore, KEGG analysis discovered the enrichment of neuroactive ligand-receptor interaction and estrogen signaling pathways, indicating the involvement of neuroendocrine in stress response. Moreover, architecture impairment in hepatopancreas tissue verified the accumulation of metabolic disturbance. Altogether, these findings indicate that neuroendocrine system mediates the flesh degradation of L. vannamei during waterless transport by disturbing the biochemical metabolic pathways and inducing architecture impairment on myofibril fibers.
Characteristics and predictors of mortality in patients with severely exacerbated COPD with acute respiratory failure
Authors: Hong Wei-Cheng , Yin Chun-Hao , Hsu Chien-Wei , Chen Jin-Shuen , Chen Yao-Shen
Published: June 2022

Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease associated with high mortality when acutely exacerbated. However, the mortality may be higher in patients needing mechanical ventilation due to severely exacerbated COPD with acute respiratory failure. Hence, we performed a cohort study to investigate the predictors in these patients.Methods: We retrospectively reviewed medical records of patients diagnosed with exacerbated COPD with acute respiratory failure, who had been treated with invasive mechanical ventilation or noninvasive positive pressure ventilation (NIPPV). We included patients admitted to our hospital, Kaohsiung Veterans General Hospital in Taiwan, from January 2011 to December 2021. Patients were excluded if they were aged below 20 years or had incomplete clinical or laboratory test data.Results: We found that the 30-day in-hospital mortality rate was 20% after ventilation in patients with severely exacerbated COPD with acute respiratory failure. Patients with age ≥70 years (P: 0.007, adjusted odds ratio (aOR): 2.21, 95% confident interval (CI): 1.25–3.92), shock (P < 0.001, aOR: 4.39, 95% CI: 2.26–8.55), high serum lactate > 4 mmole/L (P: 0.008, aOR: 2.82, 95% CI: 1.31–6.07), PaCO2 < 50 mmHg (P: 0.003, aOR: 2.35, 95% CI: 1.33–4.14), and NIPPV (P < 0.001, aOR: 4.24, 95% CI: 2.29–7.84) were independent predictors for higher 30-day in-hospital mortality rate in stepwise logistic regression analysis.Conclusions: We identified clinical predictors of mortality in patients with severely exacerbated COPD with acute respiratory failure. Age ≥70 years, shock, high serum lactate > 4 mmol/L, PaCO2 < 50 mmHg, and NIPPV were associated with higher 30-day in-hospital mortality rates in these patients.
Double Counting in Mystery: Journey of Intermediate Products in Multi-Country Trade
Authors: BIYIK ONUR
Published: June 2022

This study analyzes the production concept of the Value-Added (VA) chain by applying an alternative framework, as this concept is the main driver of the VA embodied in the intermediate export. VA supply chain spillover (upstream and downstream) of the production activities is investigated. The focal point of this study is to extend Global Value Chains (GVC) based on the multilevel and bilateral trade flow. In brief, there are two main contributions of this paper; the first begins with the originality of this work’s theory which reveals the intermediate input journey among sector-country pairs, and the second is to introduce the optimal GVC participation with the knowledge spillover effect regarding vertical (upstream and downstream) integration. In other words, this paper found that different forms of the VA with traveled products (among countries) provide more precise (sectoral/regional) integration and optimal estimation method. This paper relies on constructed Global Trade Analysis Project Multi-Region Input-Output (GTAP-MRIO) and patent panel datasets. As a result of the analysis, if the product crosses the border only twice as the product returns home to its origin country, the export/import coefficient of the sectoral linkages, which boosts VA and then causes double-counting, is about 1.54 % in terms of (single) country-level data. More importantly, with regard to its contributions with the knowledge spillover effect, traveling products among countries as twice or infinity is to contribute by 1.6% or 154%. Lastly, its contribution to VA presents 0.8% to 72%.
Level Line Trees on 2D Voronoi Diagrams
Authors: Song Yuqing , Tao Rui
Published: June 2022

We present a topdown algorithm to compute the level line tree of a 2D point set with a Voronoi diagram and scalar values. A level line is a boundary of a component of an upper/lower level set. All level lines are nested to form a tree, called the level line tree. The running time of the algorithm is O (n + L), where n is the size of the input data, L is the total length of all level lines, and the length of a level line is measured by the number of Voronoi edges in it. The efficiency of the algorithm is illustrated by experiments.
Construction and yield optimization of a cinnamylamine biosynthesis route in Escherichia coli
Authors: Wang Qi , Ma Linlin , Wang Zhiguo , Chen Quan , Wang Qian , Qi Qingsheng
Published: June 2022

BackgroundWith the development of metabolic engineering and synthetic biology, the biosynthesis of aromatic compounds has attracted much attention. Cinnamylamine is an aromatic compound derived from l-phenylalanine, which is used in the synthesis of biologically active molecules, including drugs, and energetic materials. Cinnamylamine has been mainly synthesized by chemical methods to date, and few reports have focused on the biosynthesis of cinnamylamine. Therefore, it is desirable to establish an efficient biosynthesis method for cinnamylamine.ResultsThe ω-aminotransferase Cv-ωTA from Chromobacterium violaceum has been demonstrated to have high enzyme activity in the conversion of cinnamaldehyde to cinnamylamine. To prevent the preferable conversion of cinnamaldehyde to cinnamyl alcohol in wild-type Escherichia coli, the strain MG1655 (RARE) in which six aldehyde ketone reductase and alcohol dehydrogenase genes have been knocked out was employed. Then, the carboxylic acid reductase from Neurospora crassa (NcCAR) and phosphoubiquitinyl transferase (PPTase) from E. coli were screened for a high conversion rate of cinnamic acid to cinnamaldehyde. To shift the equilibrium of the reaction toward cinnamylamine, saturation mutagenesis of Cv-ωTA at key amino acid residues was performed, and Cv-ωTA Y168G had the highest conversion rate with 88.56 mg/L cinnamylamine obtained after 4 h of fermentation. Finally, by optimizing the substrates and the supply of the cofactors, PLP and NADPH, in the fermentation, the yield of cinnamylamine in engineered E. coli reached 523.15 mg/L.ConclusionWe achieved the first biosynthesis of cinnamylamine using cinnamic acid as the precursor in E. coli using a combinatorial metabolic engineering strategy. This study provides a reference for the biosynthesis of other amine compounds and lays a foundation for the de novo synthesis of cinnamamine.
Partition Minimization Technique
Authors: Das Arghya Ranjan
Published: June 2022

There are various algorithms to find the minima of a function, most of them are based on calculating the gradients and using them to find and approximate minima. In this work we will look at a numerical algorithm to find the minimum value of a function, since it is a numerical algorithm hence it does not requires calculation of any gradients. Also the error in the solution decreases exponentially fast with each iteration, thus a highly accurate result can be generated within a small number of iterations. In this algorithm we successively partition the search domain to reduce its size with each iterations and ultimately giving the minimum value within some error limits. Though the algorithm presented here is to find an minima in a given search domain, but with proper parameters it can be used to find the global minima in the search domain.
A metapopulation study of Olea europaea subsp. cuspidata in forest patches of Zobel area northern Wollo Ethiopia
Authors: Semu Araya , Bekele Tamrat , Molla Ermias
Published: June 2022

In recent years, the concept of metapopulation has acquired traction in both biological and conservation circles. The population of a metapopulation is believed to be unstructured and spatially distributed when modeling it. As a result of both natural and artificial forces, Ethiopia's forest has been fragmented and divided into smaller portions. Due to the expansion of agriculture and urbanization, forest areas have been preserved around Ethiopian Orthodox Church monasteries and churches. Species that are important to the local community are on the edge of extinction in the forest and are seeking shelter in protected or church woodlands. Olea europaea subsp. Cuspidata is a plant that is widely used by locals in different sections of the country. The study's major goal is to determine the population distribution and investigate factors that influence Olea's survival and growth. Both a plot and a comprehensive survey were used to determine the species' prevalence. The metapopulation of the Olea population in the Zobel region was studied using thirty forest patches owned by various owners. The Incidence function model was used to analyze the presence and absence data from both the dry and rainy seasons. The largest patch was 24.06 hectares in size, while the smallest was 0.9 hectares in size. The presence of mature trees in the study area was shown to be strongly influenced by the age of the patch. Forest ownership and the number of goats in the area, according to the GLM data, have a significant impact on the occurrence of Olea seedlings and saplings in the patches. The species' adult stage has been influenced by the local community, and it can only be found in old forests like church forests. Steps must be taken to improve awareness in order to increase the incidence of species planting.
Incidental Finding of Elevated Pulmonary Arterial Pressures During Liver Transplantation and Postoperative Pulmonary Complications
Authors: Joosten Alexandre , Carrier Francois Martin , Menioui Aïmane , Linden Philippe Van der , Alexander Brenton , Coilly Audrey , Golse Nicolas , Allard Marc-Antoine , Lucidi Valerio , Azoulay Daniel , Naili Salima , Toubal Leila , Moussa Maya , Karam Lydia , Pham Hung , LAUKAITYTE Edita , Amara Youcef , Minet Marc Lanteri , Samuel Didier , Sitbon Olivier , Humbert Marc , Savale Laurent , Duranteau Jacques
Published: June 2022

Background: In patients with end stage liver disease (ESLD) scheduled for liver transplantation (LT), an intraoperative incidental finding of elevated mean pulmonary arterial pressure (mPAP) may be observed. Its association with patient outcome has not been evaluated. We aimed to estimate the effects of an incidental finding of a mPAP >20mmHg during LT on the incidence of pulmonary complications.Methods: We examined all patients who underwent a LT at Paul-Brousse hospital between January 1,2015 and December 31,2020. Those who received: a LT due to acute liver failure, a combined transplantation, or a retransplantation were excluded, as well as patients for whom known porto-pulmonary hypertension was treated before the LT or patients who underwent a LT for other etiologies than ESLD. Using right sided pulmonary artery catheterization measurements made following anesthesia induction, the study cohort was divided into two groups using a mPAP cutoff of 20mmHg. The primary outcome was a composite of pulmonary complications. Univariate and multivariable logistic regression analyses were performed to identify variables associated with the primary outcome. Sensitivity analyses of multivariable models were also conducted with other mPAP cutoffs (mPAP ≥ 25 mmHg and ≥ 35 mmHg) and even with mPAP as a continuous variableResults: Of 942 patients who underwent a LT, 659 met our inclusion criteria. Among them, 446 patients (67.7%) presented with an elevated mPAP (mPAP of 26.4±5.9mmHg). When adjusted for confounding factors, an elevated mPAP was not associated with a higher risk of pulmonary complications (adjusted OR: 1.16; 95%CI 0.8-1.7), nor with 90 days-mortality or any other complications. In our sensitivity analyses, we observed a lower prevalence of elevated mPAP when increasing thresholds (235 patients (35.7%) had an elevated mPAP when defined as ≥ 25 mmHg and 41 patients (6.2%) had an elevated mPAP when defined as ≥ 35 mmHg). We did not observe consistent association between a mPAP ≥ 25 mmHg or a mPAP ≥ 35 mmHg and our outcomes.Conclusion: Incidental finding of elevated mPAP was highly prevalent during LT, but it was not associated with a higher risk of postoperative complications.
Correlations between serum levels of microRNA-148a-3p and microRNA-485- 5p and the progression and recurrence of prostate cancer
Authors: He Wenyan , Zhang Furong , Jiang Feng , Liu Huan , Wang Gang
Published: June 2022

Background: Unpredicted postoperative recurrence of prostate cancer, one of the most common malignancies among males worldwide, has become a prominent issue-affecting patients after treatment. Here, we investigated the correlation between the serum miR-148a-3p and miR-485-5p expression levels and cancer recurrence in PCa patients, aiming to identify new biomarkers for diagnosis and predicting postoperative recurrence of prostate cancer. Methods: 198 male PCa cases treated with surgery, postoperative radiotherapy, and chemotherapy were involved in the presented study. Serum levels of miR-148a-3p and miR-485-5p were measured before the initial operation for the involved cases, which were then followed up for two years to monitor the recurrence of cancer to split the cases into recurrence and non-recurrence groups. Comparison of the relative expressions of serum miR-148a-3p and miR-485-5p were made and related to other clinic pathological features. Results: Pre-surgery serum levels of miR-148a-3p in patients with TNM stage I~II prostate cancer (Gleason score < 7) were significantly lower (P < 0.05) than levels in patients with TNM Classification of Malignant Tumors (TNM) stage III~IV cancer (Gleason score ≥7)while pre-surgery serum levels of miR-485-5p in patients with TNM stage I~II prostate cancer (Gleason score < 7) were significantly higher (P < 0.05) than patients with TNM stage III~IV cancer (Gleason score ≥ 7). Serum miR-148a-3p level in recurrence group is higher than the non-recurrence group (P < 0.05) while serum miR-485-5p level in recurrence group is lower than non-recurrence group (P < 0.05). ROC curve analysis showed the AUCs of using miR-148a-3p, miR-485-5p, and combined detection for predicting recurrence of prostate cancer were 0.825 (95% CI: 0.765 -0.875, P < 0.0001), 0.790 (95% CI: 0.726 -0.844, P < 0.0001), and 0.913 (95%CI: 0.865 -0.948, P < 0.0001). Conclusion: Pre-surgery serum miR-148a-3p level positively correlates while miR-485-5p level negatively correlates with prostate cancer's progressing and postoperative recurrence. Both molecules show potential to be used for predicting postoperative recurrence individually or combined.
Machine Learning Framework for Porcine Reproductive and Respiratory Syndrome Outbreak Forecasting
Authors: Shamsabardeh Mohammadsadegh , Martínez-López Beatriz , O’Hara Kathleen C. , Gomez Jose Pablo , Liu Xin
Published: June 2022

Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the most challenging and costly viral infectious diseases impacting the swine industry. The disease transmission pathways for PRRS are very complex, requiring a combined approach of intensive surveillance (i.e., testing), biosecurity, and vaccination for control and eradication. This study builds a proactive framework to forecast the risk of having a PRRS outbreak on a farm. This forecasting allows for early detection of disease outbreaks and could direct risk-based, and thus more cost-effective, interventions. Machine learning algorithms were trained using multi-scale data (pig group-, farm-, and area-level data). For the first time, on-farm, between-farm, and environmental variables, including farm location, pig movements, production parameters, diagnostic data, and climatic information, were combined for the prediction of PRRS outbreaks. Multi-scale datasets were merged via feature extraction, followed by the wrapper and filter feature selection, to find those feature subsets with the best forecasting performance. The predictive value of each feature selection mechanism was evaluated in terms of its stability. Numerical results demonstrate good forecasting performance in terms of area under the ROC curve.
Stratification analysis reveal associations between CYP2B6 polymorphisms and lung cancer susceptibility in Chinese Han population
Authors: Yang Shuangyu , Zhang Wenjie , Meng Wenting , Dou Xia , Jin Tianbo
Published: June 2022

Background: Recently, many clinical studies have demonstrated that Cytochrome P450 (CYP) is related to the occurrence and development of many cancers. The purpose of our study is to clarify the relevance of CYP2B6 single nucleotide polymorphisms (SNPs) to lung cancer susceptibility.Methods: Five SNPs in CYP2B6 were genotyped in the Han population of China including 507 cases and 505 controls using Agena MassARRAY. Using odds ratio, 95% confidence interval, and χ2 test to calculate the relationship between the SNPs and LC susceptibility. The SNP-SNP interactions were analyzed by performing multifactor dimensionality reduction (MDR).Results: We found that rs2099361 was associated with an increased susceptibility to LC in the codominant model (OR = 1.31, p = 0.045). After stratification analysis, the results found that CYP2B6 rs4803418 (BMI > 24 kg/m2), rs4803420 (BMI > 24 kg/m2, No-smoking), rs12979270 (BMI > 24 kg/m2), and rs1038376 (III-IV versus I-II) were significantly associated with decreased susceptibility of LC. Inversely, rs4803418 (BMI > 24 kg/m2), rs4803420 (III-IV versus I-II) and rs12979270 (No-smoking) showed increased susceptibility to LC. Furthermore, the result of MDR showed that a synergistic relationship might exist between rs12979270, rs4803420, rs2099361, rs1038376, and rs4803418 in CYP2B6 gene and the pathophysiology and genetics of LC. Conclusions: The results suggest that SNPs of CYP2B6 have crucial roles in LC susceptibility, and its correlation is related to the patients’ BMI, smoking status, and clinical stages.
Galilius: A Simple Simulation Model of Spiral Galaxies
Authors: MANSOUR El Houssain AIT , MANSOUR El Houssain AIT
Published: June 2022

Galaxy morphology classification plays a significant role in the galaxy’s evolution. The existence of spiral arms and bars classification of the Hubble sequence is a misunderstood problem. The most previous studies disagree on the role of coherent and chaotic orbital structures on galaxy spirals and bar formation. This article suggests a cyclic galaxy simulation model based-on star motions. We implement approximated velocity curves with various parameters. We provide a brief overview of galaxy model flowchart. We show that phase synchronization of stars at initial conditions has a major effect on spiral arms and bar development. In addition, the irregular galaxy shape occurs among chaotic initial conditions or random velocities. We also highlight the model accretion factor α and its linking with stars accretion and galaxy morphology transformation. The proposed model image datasets and simulation tutorials are available on Galilius.com.
Photo-thermal tuning of integrated optical waveguides coated with 2D graphene oxide thin films
Authors: Moss David
Published: June 2022

We experimentally investigate power-sensitive photo-thermal tuning (PTT) of two-dimensional (2D) graphene oxide (GO) films coated on integrated optical waveguides. We measure the light power thresholds for reversible and permanent GO reduction in silicon nitride (SiN) waveguides integrated with 1 and 2 layers of GO. Raman spectra at different positions of a hybrid waveguide with permanently reduced GO are characterized, verifying the inhomogeneous GO reduction along the direction of light propagation through the waveguide. The differences between the PTT induced by a continuous-wave laser and a pulsed laser are also compared, confirming that the PTT mainly depend on the average input power. These results reveal interesting features for 2D GO films coated on integrated optical waveguides, which are of fundamental importance for the control and engineering of GO’s properties in hybrid integrated photonic devices.
Multilevel linear and temporal analyses on the effects of weather indices on movements and behaviors
Authors: Herbuela Von Ralph Dane Marquez , Karita Tomonori , Toya Akihiro , Furukawa Yoshiya , Senba Shuichiro , Onishi Eiko , Saeki Tatsuo
Published: June 2022

Weather indices significantly affecting movements, affective, and behavioral states remain largely unknown among children with profound or severe intellectual and multiple disabilities (PIMD/IDs). Main, seasonal interaction and 24-hour time-offsets effects of outdoor weather indices on the movements and behaviors of children with PIMD/IDs were explored using hierarchical and general linear models. Caregiver-interpreted facial, body, and limb movements and behaviors of 20 8-to 16-year-old children with PIMD/IDs and simultaneous online-API-and-sensor-collected app-based weather, proximity and time data were collected in 105 single-dyad video-recorded (30-hour) natural-child-caregiver-dyadic interactions over 5 months. Fluctuations in outdoor atmospheric pressure, humidity, cloudiness, wind speed, season, daylength, time (12 to 1 pm), and conditions were predictive of variations in movements and behaviors, which in turn, also responded to increased indoor UV, humidity, and cloudiness levels during winter, and increasing atmospheric pressure and decreasing humidity during fall. While outdoor temperature, atmospheric pressure, humidity, and cloudiness immediately affected variations in movement and behavior outcomes, time-offset wind-related indices had significant delayed effects at several time lags. Evidently, variations in movements and behaviors of children with PIMD/IDs are affected by seasonal variations and current or delayed fluctuating levels of outdoor weather indices which has significant implications for communication and educational interventions.
Evaluation of cardiac toxicity with ponatinib using a spontaneous reporting database
Authors: Kanbayashi Yuko , Uchida Mayako , Nakano Kana , Wakabayashi Haruka , Shimizu Tadashi
Published: June 2022

This study aimed to determine the risk of ponatinib-induced cardiac toxicity, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. We analyzed data for the period between April 2004 and March 2021. Data on cardiac toxicities were extracted, and relative risk of adverse events (AEs) was estimated using the reporting odds ratio. We analyzed 1,772,494 reports and identified 1,152 reports of AEs caused by ponatinib. Of these, 163 cardiac toxicities were reportedly associated with ponatinib. Signals were detected for thirteen cardiac toxicities: hypertension, cardiac failure, acute cardiac failure, atrial fibrillation, increased blood pressure, coronary artery stenosis, myocardial infarction, angina pectoris, pulmonary hypertension, prolonged QT on electrocardiography, cardiomyopathy, cardiac dysfunction, and acute myocardial infarction. Among these, hypertension was the most frequently reported AE (27.6%). A histogram of times to onset showed occurrence from 4.5 to 150.5 days. Hypertension, cardiac failure, coronary artery stenosis, and myocardial infarction could potentially result in serious outcomes and some cases occurred earlier or even more than 1 year after starting administration. In conclusion, patients should be monitored for signs of the onset of these AEs not only at the start of ponatinib administration but also over the longer term.
Comparative studies of two AA10 family lytic polysaccharide monooxygenases from Bacillus thuringiensis
Authors: Zhang Huiyan , Zhou Haichuan , Zhao Yong , Li Tang , Yin Heng
Published: June 2022

Lytic polysaccharide monooxygenases (LPMOs) are a group of copper-dependent enzymes that depolymerize recalcitrant polysaccharides via an oxidative mechanism. However, the biological reasons that could be accounted for this diversity remains largely unknown. In previous reports, two chitin-active LPMOs from Bacillus thuringiensis, BtLPMO10A and BtLPMO10B, have been preliminarily characterized. However, some important biochemical features and substrate preference, as well as their potential applications in chitin degradation, still deserve further investigation. Results from present study showed that both BtLPMO10A and BtLPMO10B exhibit similar catalytic domains as well as highly conserved substrate-binding planes. However, unlike BtLPMO10A, which has comparable binding ability to both crystalline and amorphous form of chitins, BtLPMO10B exhibited much stronger binding ability to colloidal chitin, which mainly attribute to its carbohydrate-binding module-5 (CBM5). Interestingly, the relative high binding ability of BtLPMO10B to colloidal chitin does not lead to high catalytic activity of the enzyme. In contrast, the enzyme exhibited higher activity on β-chitin. Further experiments showed that the binding of BtLPMO10B to colloidal chitin was mainly non-productive, indicating a complicated role for CBM5 in LPMO activity. Furthermore, synergistic experiments demonstrated that both LPMOs boosted the activity of the chitinase, and the higher efficiency of BtLPMO10A can be override by BtLPMO10B.
Preparation of Therapy-Grade Extracellular Vesicles from Adipose Tissue to Promote Diabetic Wound Healing
Authors: Pan Chuqiao , Xu Peng , Zheng Yi , Wang Yikai , Chen Chuhsin , Fu Shibo , Liu Zibo , Chen Yahong , Xue Ke , Liu Kai
Published: June 2022

Background
Treatment of diabetic wounds is a major challenge in clinical practice. Extracellular vesicles (EVs) from adipose-derived stem cells (ADSCs) have shown effectiveness in diabetic wound models. However, obtaining ADSC-EVs requires culturing vast numbers of cells, which is hampered by the need for expensive equipment and reagents, extended time cost, and complicated procedures before commercialization. Therefore, methods to extract EVs from discarded tissue need to be developed, for immediate application during surgery. For this reason, mechanical, collagenase-digestive, and effused methods were designed and compared for preparing therapy-grade EVs directly from adipose tissue.
Methods
Characteristics and quantities of EVs were detected by transmission electron microscopy, nanoparticle tracking analysis, and western blotting firstly. To investigate the biological effects of EVs on diabetic wound healing, angiogenesis, proliferation, migration, and inflammation-regulation assays were then evaluated in vitro, along with a diabetic wound healing mouse model in vivo. To further explore the potential therapeutic mechanism of EVs, miRNA expression profile of EVs were also identified and analyzed.
Results
The adipose tissue derived EVs (AT-EVs) were showed to qualify ISEV identification by NTA and western blotting and the AT-EVs yield from three methods was equal. EVs also showed promoting effects on biological processes related to diabetic wound healing, which depend on fibroblasts, keratinocytes, endothelial cells, and macrophages both in vitro and in vivo. We also observed enrichment of overlapping or unique miRNAs associated with diabetic wound healing for further investigation.
Conclusion
After comparative analyses, a mechanical method was proposed for preparing immediate clinical applicable EVs from adipose tissue that would result in reduced preparation time and lower cost, which could have promising application potential in treating diabetic wounds.
The α-hemolysis negative CC59 clone of Methicillin-resistant Staphylococcus aureus isolates from Beijing，China
Authors: Wang Lijuan , Sun Chen , Qian Suyun , Liu Yingchao , Yao Kaihu , Dong Fang
Published: June 2022

Staphylococcus aureus is one of the most famous bacterial pathogens, it is a leading causative agent in skin and invasive infections. We analyzed the hemolytic patterns of MRSA isolates from Beijing Children’ hospital and found that most CC59 isolates were α hemolysis negative. In this study, we tried to find the possible reason for α hemolytic deletion in CC59 isolates. Hemolysis patterns of different MRSA types were showed. We have knocked out hlα gene of R23 isolate to form R23Δhlα isolate. A differential expression of hlα gene was examined among isolates with different hemolysis phenotypes using RT-PCR. We have examined the secretion of Hlα of R23, USA300 and R23Δhlα by Western blot. A high-copy-number plasmid containing the hlα gene was utilized to restore expression of α hemolysin.During the four periods (2009-2011, 2012-2013, 2016, 2017), 290 MRSA isolates were collected in Beijing Children’s Hospital (BCH). Most of the ST59 isolates (94.38%), and nine of the ST338 isolates (100%) showed negative α hemolysis phenotype. Both of them belong to CC30 clone. Transcriptional levels of hlα were equal among isolates showing α, δ hemolysis and β, δ hemolysis. R23 did not show α hemolysis phenotype but it produced Hlα. High-copy-number plasmid containing the hlα gene could restore α hemolysis phenotype of R23Δhlα isolate.This study elucidated that the negative α hemolysis in CC59 isolates was not related to Hlα protein production. However, over-production of Hlα could restore the α hemolytic activity. β hemolysin worked well in CC59 clone.
Sequencing of hsp70 for discernment of species from the Leishmania (Viannia) guyanensis complex from endemic areas in Colombia
Authors: Hoyos Juliana , Rosales-Chilma Mariana , Leon Cielo , Gonzalez Camila , Gomez Maria Adelaia
Published: June 2022

Background: Colombia reports one of the highest numbers of endemic Leishmania species (n=9) causing human disease. Although much effort has been devoted to generating simple and specific tools for Leishmania species identification, challenges remain in the discrimination of species belonging to the Leishmania (Viannia) guyanensis complex: L. (V.) guyanensis and L. (V.) panamensis.Methods: A set of seven reference strains of species pertaining to the L. Leishmania and L. Viannia subgenera, clinical strains from human cases of cutaneous leishmaniasis (CL, n=26), and samples collected from sylvatic mammals and sandflies (n=7) from endemic areas in Colombia were included in this study. The hsp70 gene was PCR-amplified from DNA extracts of logarithmic phase promastigotes or tissue samples, and PCR products were sequenced. Sequence alignment was performed against a set of previously published and curated sequences, and phylogenetic analysis based on maximum-likelihood and Bayesian inference approaches was conducted. Haplotypic diversity among strains and species of the L.(V.) guyanensis complex was explored using a median-joining network. Results: Sequencing of the hsp70 gene for L.Viannia species typing was comparable to species identification using isoenzyme electrophoresis or monoclonal antibodies. Complete species matching was found, except for one sylvatic sample with an identity yet unsolved. Among the L. (V.) panamensis clinical strains, we found two distinctive phylogenetic clusters correlated with two different zymodemes, L.(V.) panamensis Z2.2 and Z2.3. Analysis of samples from sylvatic environments identified novel records of wild mammals and sandflies species naturally infected.Conclusions: Our results support the adequacy of hsp70 gene sequencing as a single locus approach for discrimination of L.Viannia species, as well as for exploring the genetic diversity within the L. (V.) guyanensis complex.
Predictors of the degree of ventricular catheter obstruction: duration of implantation, number of prior revision surgeries, contact with the ventricular wall and the surgical approach
Authors: Hariharan Prashant , Gluski Jacob , Sondheimer Jeffrey , Petroj Alexandra , Jea Andrew , Whitehead William E , Bigio Marc R. Del , Marupudi Neena I. ,   James P. McAllister 2nd, Limbrick David , Rocque Brandon G , Harris Carolyn A
Published: June 2022

The authors have requested that this preprint be removed from Research Square.
RegentK regenerative treatment available for ruptured anterior cruciate ligament? A scoping review
Authors: Tedeschi Roberto
Published: June 2022

Background
Conservative/regenerative therapy for cruciate ligament ruptures can be considered as primary treatment. However, nowadays, the first option is almost always only surgical, although studies on the efficacy of intervention exist in the literature.
Aim
This scoping review aimed to map and summarise the literature to identify interventions with Regentk therapy available for cruciate ligament ruptures.
Methods
Four databases were searched until May 2022. Studies that considered anterior cruciate ruptures treated with the Regentk method could be included. All interventions and contexts were considered. No restrictions were applied regarding language, study design and publication type. No grey literature and reference lists of included articles were identified. Results were presented in numerical and thematic form.
Results
Da 245 record iniziali, 7 studi hanno soddisfatto i criteri di inclusione. La maggior parte degli articoli erano RCT e prendevano in considerazione pazienti sportivi con rottura del legamento crociato. Gli autori hanno discusso una sola gamma di interventi: conservativi (n = 7). In particolare, il trattamento conservativo/rigenerativo Regentk.
Conclusions
This is the first scoping review that provides a comprehensive overview of the topic. The results revealed clear gaps in primary research, confirming that current management is based on surgery. This review may be useful for overall management and may provide a starting point for future research.
WITHDRAWN: Effects of channel dimensions and wall properties on the performance of heat-integrated reactors
Authors: Chen Junjie
Published: June 2022

Autothermal multifunctional reactors have been a subject of vital research and development. However, the mechanisms for the effects of various design factors on heat transfer characteristics are still not fully understood. This study relates to a thermochemical process for producing hydrogen by the catalytic endothermic reaction of methanol with steam in a thermally integrated microchannel reforming reactor. Computations are carried out to better understand the specific features of coupling endothermic and exothermic reactions. The effects of wall heat conduction properties and channel dimensions on heat transfer characteristics and reactor performance are investigated. The respective considerations are presented and discussed for different modes of operation. The results indicate that maximum temperature control is the key issue in coupling endothermic and exothermic reactions in an autothermal mode of operation. The rate of the hydrogen production reaction is limited by the ability to remove heat from the reactor. Reaction heat flux profiles are considerably affected by channel dimensions. The peak reaction heat flux increases with the channel dimensions while maintaining the flow rates. The thermal conductivity of the channel walls is fundamentally important. Materials with high thermal conductivity are preferred for the channel walls. Thermally conductive ceramics and metals are well-suited. Wall materials with poor heat conduction properties degrade the reactor performance. Design recommendations are made to improve thermal performance for the reactor. Improved heat removal could dramatically increase the throughput of the heat-integrated reactor. Nearly complete methanol conversion to hydrogen is achieved and the rate of conversion is high due to the excellent heat conduction properties of the channel walls.
Socio-economic impact of COVID-19 pandemic lockdown in Ota, Ogun State, Nigeria
Authors: Akinpelu Olusegun Peter , Owolabi Muhydeen Adedeji , Kilasho Omotunde Musiliudeen
Published: June 2022

The study analysis socio-economic impact of COVID-19 pandemic lockdown as perceived by the residents in different residential zones of Ota, Ogun State, Nigeria, this is aimed at proffering recommendations that guide policy framework. The study adopted survey approach. Data for the study were obtained through questionnaire administration. The study area, Ota, was stratified into three residential zones (Core, transition and sub-urban). Using systematic sampling technique, 229 residents from 2% of residential buildings were sampled in the study area. Data collected were analysed with the use of descriptive and inferential statistics. Results of the study established that majority (63.7%) did not believed in the existence of COVID-19 pandemic, while 63.8% of the residents claimed that COVID-19 pandemic was not severe in the area. Over 60% of the residents affirmed that existence of COVID-19 is a political scam. It was found that 66.8% of the residents confirmed that the lockdown had negative impact on the economy of the area. Residents perceived increased incidence of social vices as a result of COVID-19 pandemic lockdown. The COVID-19 pandemic lockdown index (CPLI) reveals theft incidence (4.41), domestic violence (3.85) and less social gathering (3.98) recorded highest index in core, transition and sub-urban respectively. However, the lockdown has least impact on governments’ palliative to the residents. It can be established that there is a no significant variation in the impact of COVID-19 pandemic lockdown in the three residential zones (p < 0.05). It is therefore, recommended that appropriate machinery for effective monitoring and feedback on governments’ intervention programme should be given needed priority.
HbA1c range determination for diabetes treatment in Google Cloud Compute Engine and SerpAPI
Authors: VALAVANDAN RAMAMURTHY , Mukherjee Surasa , R Vijay
Published: June 2022

In this paper, we have taken a use case in the healthcare domain for the determination of factors for an accurate range of HbA1c in diabetics’ treatment. Google Search Engine Application Program Interface (API), SerpAPI@ is evaluated for the execution of Compute engine in Google cloud. As a service in Infrastructure as a Service (IaaS), the Compute Engine gives the accurate value in HbA1c in the work orchestration in Airflow (astronomer) of Apache and Cloud Composer. We have also developed the application layer for every work stream in python and application output is stored in Google Cloud Storage. The accuracy of diabetic range determination is calculated in python as a measure for the healthcare practitioner to provide the right line of treatment for diabetic patients. A python program is developed to connect to the Google Search with a wrapper of SerpAPI in the Google Cloud Scheduler and create the JSON file schema for parameterization of Search Engine API. The results are shared with customers in the healthcare domain. We have also addressed the challenges of diabetic treatment during long-term Covid-19.
Enhancement of the Mechanical Properties of a Geopolymer Concrete Due to Chemical and Microstructural Interaction of the Binder Material
Authors: Karthikadevi S , Saraswathi.R
Published: June 2022

Many experimentation and researchers were made in the recent decades in concrete and advancement in the field of concrete technology were given a major focus. There are so many alternative materials that were identified and researches were carried out for better understanding. In this study, the binder which is to be cement basically is replaced with a combination of Alccofine-1203(A), Metakaolin (MK), and Ground Granulated Blast-furnace Slag (GGBS) in different ratios to arrive a geopolymer concrete mix. In addition, the study also focuses on the chemical interaction of the replacement material and its microstructure interaction. The liquid binder (l/b) ratios varied between 0.48 to 0.54, and about seven geopolymer concrete mixes were arrived and experimental investigation done for mechanical property. The maximum compressive strength obtained from the mix proportions G50M35A15 at an l/b ratio of 0.50 was taken as a mix design for the Geopolymer mix. The identified combination of Granulated Blast-furnace Slag, Metakaolin, Alccofine-1203 (GMA) is used for further study. The experimental study was conducted by casting specimens for evaluating compressive strength, tensile strength and flexural behaviour. It is found that the experimental results proves that there is a significant hike in the mechanical behaviour of the concrete. The microstructure investigation is done by SEM analysis and energy dispersive X-ray analysis (EDAX). The SEM images also indicated a good interlocking characteristics of the materials which in turn directly impacts the mechanical properties of the concrete.
Screening anlotinib responders via blood-based proteomics in non-small cell lung cancer
Authors: Lu Jun , Zhang Wei , Yu Keke , Zhang Lele , Lou Yuqing , Gu Ping , Nei Wei , Qian Jie , Xu Jun , Wang Huimin , Zhong Hua , Han Baohui
Published: June 2022

Anlotinib has been demonstrated to be effective in advanced non-small cell lung cancer (NSCLC) patients. The response stratification of anlotinib remains unclear. In this study, plasma samples from 28 anlotinib-treated NSCLC patients (discovery cohort: 14 responders and 14 non-responders) were subjected to proteomic analysis, and plasma samples from 35 anlotinib-treated NSCLC patients (validation cohort) were subjected to validation analysis. Liquid chromatography-tandem mass spectrometry analysis was performed on samples with different time points, namely baseline (BL), best response (BR), and progression disease (PD). Bioinformatics analysis was performed to screen for the underlying differential proteins. Enzyme-linked immunosorbent assay was performed to detect plasma ARHGDIB, FN1, CDH1, and KNG1 levels respectively. The Kaplan-Meier survival analysis was used for biomarker-based responsive stratification. Our results indicated that differential proteins between responders and non-responders showed that proteomic technology potentially contributes to biomarker screening in plasma samples at BL. Furthermore, our results suggested that the detection of plasma ARHGDIB, FN1, CDH1, and KNG1 levels have potential predictive value for anlotinib response both in discovery cohort and validation cohort. Collectively, this study offers novel insights into the value of plasma biomarker screening via proteomic examination and suggests that plasma ARHGDIB, FN1, CDH1, and KNG1 levels could be used as biomarkers for anlotinib stratification in NSCLC patients.