bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinesin and Myosin Motors Compete to Drive Rich Multi-Phase Dynamics in Programmable Cytoskeletal Composites
Authors: Achiriloaie Daisy , Currie Christopher , Michel Jonathan , Hendija Maya , Lindsay K Alice , Bolef Nadia Schwartz , Lee Gloria , Rust Michael , Sheung Janet , Das Moumita , Ross Jennifer , McGorty Ryan , Robertson-Anderson Rae
Published: January 2022

The cytoskeleton of biological cells relies on a diverse population of motors, filaments, and binding proteins acting in concert to enable non-equilibrium processes ranging from mitosis to chemotaxis. The cytoskeleton’s versatile reconfigurability, programmed by interactions between its constituents, make it a foundational active matter platform. However, current active matter endeavors are limited largely to single force-generating components acting on a single substrate – far from the composite cytoskeleton in live cells. Here, we engineer actin-microtubule composites, driven by kinesin and myosin motors and tuned by crosslinkers, that restructure into diverse morphologies from interpenetrating filamentous networks to de-mixed amorphous clusters. Our Fourier analyses reveal that kinesin and myosin compete to delay kinesin-driven restructuring and suppress de-mixing and flow, while crosslinking accelerates reorganization and promotes actin-microtubule correlations. The phase space of non-equilibrium dynamics falls into three broad classes– slow reconfiguration, fast advective flow, and multi-mode ballistic dynamics – with structure-dynamics relations described by the relative contributions of elastic and dissipative responses to motor-generated forces.
Using Machine Learning to Discover Unexpected Patterns in Clinical Data: A Case Study in COVID-19 Sub-cohort Discovery
Authors: Cowley Hannah Paris , Robinette Michael S. , Matelsky Jordan K. , Xenes Daniel , Kashyap Aparajita , Ibrahim Nabeela F. , Robinson Matthew L. , Zeger Scott , Garibaldi Brian T. , Gray-Roncal William
Published: January 2022

As clinicians are faced with a deluge of new information, data science can play a key role in highlighting key features towards developing new clinical hypotheses. Indeed, insights derived from machine learning can serve as a clinical support tool by connecting care providers with results from big data analysis to identify latent patterns that may not be easily detected by even skilled human observers. In this work, we show an example of collaboration between clinicians and data scientists during the COVID-19 pandemic, identifying subgroups of COVID-19 patients with unanticipated outcomes or who are high-risk for severe disease or death. We apply a random forest classifier model to predict adverse patient outcomes early in the disease course, and we connect our classification results to unsupervised clustering of patient features that may underpin patient risk. The paradigm for using data science for hypothesis generation and clinical decision support, as well as our triage classification approach and unsupervised clustering methods to determine patient cohorts, are applicable to driving rapid hypothesis generation and iteration in a variety of clinical challenges, including future public health crises.
The Addition of Epistatic Genetic Effects Increases Genomic Prediction Accuracy for Reproduction and Production Traits in Duroc Pigs Using Genomic Models
Authors: Cheng Jian , Tiezzi Francesco , Howard Jeremy , Maltecca Christian , Jiang Jicai
Published: January 2022

Background: Genomic selection has been implemented in livestock genetic evaluations for years. However, currently most genomic selection models only consider the additive effects associated with SNP markers and nonadditive genetic effects have been for the most part ignored. Methods: Production traits for 26,735 to 27,647 Duroc pigs and reproductive traits for 5,338 sows were used, including off-test body weight (WT), off-test back fat (BF), off-test loin muscle depth (MS), number born alive (NBA), number born dead (NBD), and number weaned (NW). All animals were genotyped with the PorcineSNP60K Bead Chip. Variance components were estimated using a linear mixed model that includes inbreeding coefficient, additive, dominance, additive-by-additive, additive-by-dominance, dominance-by-dominance effect, and common litter environmental effect. Genomic prediction performance, including all nonadditive genetic effects, was compared with a reduced model that included only additive genetic effect. Results: Significant estimates of additive-by-additive effect variance were observed for NBA, BF, and WT (31%, 9%, and 10%, respectively). Production traits showed significant large estimates of additive-by-dominance variance (9%-23%). MS also showed large estimate of dominance-by-dominance variance (10%). Dominance effect variance estimates were low for all traits (0%-2%). Compared to the reduced model, prediction accuracies using the full model, including nonadditive effects, increased significantly by 12%, 12%, and 1% for NBA, WT, and MS, respectively. A strong dominance association signal with BF was identified near AK5.Conclusions: Sizable estimates of epistatic effects were found for the reproduction and production traits, while the dominance effect was relatively small for all traits yet significant for all production traits. Including nonadditive effects, especially epistatic effects in the genomic prediction model, significantly improved prediction accuracy for NBA, WT, and MS.
Three-dimensional Alignment of the Upper Extremity in the Standing Neutral Position in Healthy Subjects
Authors: Yoshida Yuki , Matsumura Noboru , Yamada Yoshitake , Hiraga Satoshi , Ishii Kazunori , Oki Satoshi , Yokoyama Yoichi , Yamada Minoru , Nakamura Masaya , Nagura Takeo , Jinzaki Masahiro
Published: January 2022

Background: Though alignment of the spine and lower extremities in the standing neutral position has been evaluated, a few studies evaluating the alignment of the upper extremities have also been made. This study assessed the normal alignment of the upper extremities in the standing neutral position and clarified the three-dimensional angular rotations of the upper extremity joints.Methods: Computed tomography (CT) images of 158 upper extremities from 79 healthy volunteers were prospectively acquired in the standing neutral position using an upright CT scanner. Three-dimensional coordinate systems of the thorax, scapula, humerus, and forearm were designated, and three-dimensional angular rotations of the scapulothoracic, glenohumeral, and elbow joints were calculated.Results: The mean angle of the scapulothoracic joint was 8.5° ± 5.9° of upward rotation, 28.7° ± 5.9° of internal rotation, and 7.9° ± 5.2° of anterior inclination. The mean angle of the glenohumeral joint was 4.4° ± 5.9° of abduction, 9.4° ± 12.3° of internal rotation, and 0.3° ± 4.4° of extension. The mean angle of the elbow joint was 9.6° ± 3.7° of valgus, 88.8° ± 14.3° of pronation, and 15.4° ± 4.2° of flexion. Correlations in angular rotation values were found, and interactions for keeping the upper extremities in a neutral position were observed.Conclusions: This study clarified the three-dimensional angular rotation of upper extremity joints in the standing neutral position using an upright CT scanner. Our results may provide important insights for the functional evaluation of upper extremity alignment.
Influence of Different Dielectrics on Process Performance for Electrical Discharge-Assisted Milling of Titanium Alloy
Authors: Xu Moran , Li Changping , Kurniawan Rendi , Chen Jielin , Ko Tae Jo
Published: January 2022

Electrical discharge-assisted milling (EDAM) is an effective method for machining titanium alloys according to previous research. In this study, the influence of three different dielectrics (kerosene, EDM oil, and deionized water) on the EDAM performance was studied. Experimental studies reveal the influence of different dielectrics by analyzing the discharged signal, surface morphology, and elemental composition of the electrode. The results show that kerosene and EDM oil have a higher discharge frequency than deionized water. After a long discharge time, carbides and debris were generated during the machining process, which affected the micro-hardness and the discharge stability of the machined material. In EDAM, EDM oil can produce the best surface quality, and the surface roughness value was 34.93%, 87.92%, and 121.68% higher than that of kerosene, deionized water, and conventional milling (CM), respectively.
The safety and cost-analysis of simultaneous versus staged bilateral total knee arthroplasty in a Taiwan population
Authors: Chou Te-Feng Arthur , Ma Hsuan-Hsiao , Hsu Yu-Chun , Tsai Chi-Wu , Tsai Shang-Wen , Chen Cheng-Fong , Chiu Fang-Yao , Wu Po-Kuei , Chen Tain-Hsiung , Chen Wei-Ming
Published: January 2022

The purpose of this study was to investigate the safety of Simultaneous, bilateral TKA (SiTKA). Furthermore, we also assessed the cost reduction of SiTKA in comparison with Staged, bilateral TKA (StTKA). We retrospectively review all patients that underwent SiTKA or StTKA due to osteoarthritis (OA) or spontaneous osteonecrosis of the knee (SONK).We assessed length of stay, transfusion rate, early postoperative complications, 30-day and 90-day readmission rate, 1-year reoperation rate and the indication for reoperation. Furthermore, we analyzed the total cost of the two groups, reimbursement from the national health insurance (NHI), cost of the procedures, and net income from each case. A total of 2016 patients (1565 SiTKA and 451 StTKAs) were included in this study. There were no significant differences in terms of complication rates, 30-day and 90-day readmission, and 1-year reoperations between the two groups. The total length of stay was on average 5.0 days longer for StTKA (p<0.01). In terms of cost, all categories of medical costs were significantly lower in SiTKA, while the net hospital income was significantly higher for StTKA. In conclusion, SiTKA and StTKA have similar postoperative complication, readmission and reoperation rates, while SiTKA significantly reduces medical expenses for the patient and NHI. Level of evidence: level III, retrospective cohort study
Numerical and Experimental Validation of Gas Metal Arc Welding on AISI 441 Ferritic Stainless Steel Through Mechanical and Microstructural Analysis
Authors: CARUSO SERAFINO , UMBRELLO DOMENICO
Published: January 2022

Residual stresses and strains, distortion, heat affected zone (HAZ), grain size changes and hardness variation during gas metal arc welding (GMAW), are fundamental aspects to study and control during welding processes. For this reason, numerical simulations of the welding processes represent the more frequently used tool to better analyse the several aspects characterizing this joining process with the aim to reduce lead time and production costs. In the present study an uncoupled 3D thermo-mechanical analysis was carried out by two commercial finite element method (FEM) software to model an experimental single bead GMAW of AISI 441 at different process set-up. The experimental HAZ and measured temperatures were used to calibrate the heat source of both the used numerical codes, then a validation procedure was done to test the robustness of the two developed analytical procedures. One software was used to predict the residual stresses and strains and the distortions of the welded components, while in the second software a user routine was implemented, including a physical based model and the Hall-Petch (H-P) equation, to predict grain size change and hardness evolution respectively. The results demonstrate that the predicted mechanical and microstructural aspects agree with those experimentally found showing the reliability of the two codes in predicting the thermal phenomena characterizing the HAZ during the analysed welding process.
Disrupting The Resting State: Meta-Analytic Evidence That Mindfulness Training Alters Default Mode Network Connectivity
Authors: Rahrig Hadley , Vago David R. , Passarelli Matthew , Auten Allison , Lynn Nicholas A. , Brown Kirk Warren
Published: January 2022

This meta-analysis sought to expand upon neurobiological models of mindfulness through investigation of inherent brain network connectivity outcomes, indexed via resting state functional connectivity (rsFC). We conducted a systematic review and meta-analysis of rsFC as an outcome of mindfulness training (MT) relative to structurally-equivalent programs, with the hypothesis that that MT would increase cross-network connectivity between nodes of the Default Mode Network (DMN), Salience Network (SN), and Frontoparietal Control Network (FPCN) as a mechanism of internally-oriented attentional control. Texts were identified from the databases: MEDLINE/PubMed, ERIC, PSYCINFO, ProQuest, Scopus, and Web of Sciences; and were screened for inclusion based on experimental/quasi-experimental trial design and use of standardized mindfulness-based interventions. RsFC effects were extracted from twelve studies (mindfulness n = 226; control n = 204). Voxel-based meta-analysis revealed significantly greater rsFC (MT > control) between the left middle cingulate (Hedge’s g = .234, p = 0288, I2 = 15.87), located within the SN, and the posterior cingulate cortex, a focal hub of the DMN. Egger’s test for publication bias was nonsignificant, bias = 2.17, p = .162. In support of our hypothesis, results suggest that MT targets internetwork (SN-DMN) connectivity implicated in the flexible control of internally-oriented attention.
A universal deep learning-based framework towards fully ab initio simulation of atmospheric aerosol nucleation
Authors: Jiang Shuai , Liu Yi-Rong , Huang Teng , Feng Ya-Juan , Wang Chun-Yu , Wang Zhong-Quan , Ge Bin-Jing , Liu Quan-Sheng , Guang Wei-Ran , Huang Wei
Published: January 2022

Atmospheric aerosol nucleation contributes to around half of cloud condensation nuclei globally. Despite the importance for climate, detailed nucleation mechanisms are still poorly understood. Understanding aerosol nucleation dynamics is hindered by non-reactivity of force fields and high computational costs due to rare event nature of aerosol nucleation. Developing reactive force fields for nucleation systems are even more challenging than covalently bonded materials because of wide size range and high dimensional characteristics of non-covalent hydrogen bonding bridging clusters. Here we proposes a system transferable framework to train an accurate reactive force field (FF) based on deep neural network (DNN) and further bridges the DNN-FF based molecular dynamics (MD) with cluster kinetics model based on Poisson distributions of reactive events to overcome high computational costs from direct MD. We found that previously reported acid-base formation rates tend to be underestimated several times, emphasizing acid-base nucleation observed in multiple environments should be revisited.
The Intrinsic Differences Between Immune Checkpoint Inhibitor Induced Myocarditis: A Retrospective Analysis of Real-World Data
Authors: Lei Yanna , Zheng Xiufeng , Huang Qian , Li Xiaoying , Qiu Meng , Liu Ming
Published: January 2022

Immune-related myocarditis is a severe and even life-threatening immune-related adverse event (irAE) which may also be under-estimated due to the challenge in diagnosis. There have been few reports about the intrinsic difference between patients with immune-associated myocarditis. A retrospective analysis was conducted between March 2019 to June 2020 in West China Hospital and 18 patients with immune-related myocarditis were studied. Cases were classified as mild (n=12) or severe myocarditis (n=6) according to the clinical manifestations and haemodynamic complications. Covariates extracted from medical records were compared in different groups, and factors associated with severe myocarditis were identified. In this retrospective analysis, the median age of the 18 patients was 60 years old. Most cases occur early and approximately after the first or second ICI infusion. The severity of myocarditis may be correlated with lactate dehydrogenase (LDH) (P=0.04) and troponin (P=0.0057). The relationship between troponin and myocarditis was further confirmed in another cohort which including 30 patients. In addition, patients are more likely to develop multi-irAEs, and myositis was the most common second irAE. Those who experience multi-irAEs had significantly higher LDH (P=0.02) as well as myoglobin levels (P=0.02) than did not experience. All patients were treated with steroids timely and the mortality rate was 5.6% in our study. In this study, we explore risk factors for severe myocarditis and we emphasized the importance of a multidisciplinary team in assisting diagnosis and treatment options. It is critical to initiate corticosteroid therapy, regardless of the severity of the myocarditis.
Analysis of Factors Affecting the Length of Stay in the Emergency Department for Critically Ill Patients Transferred to Regional Emergency Medical Centers
Authors: Lee Hyungbok , Lee Sangrim , Kim Hyeoneui
Published: January 2022

BackgroundTransferring an emergency patient to another emergency department (ED) is necessary when she/he is unable to receive necessary treatment from the first visited ED, although the transfer poses potential risks for adverse clinical outcomes and lowering the quality of emergency medical services by overcrowding the transferred ED. This study aimed to understand the factors affecting the ED length of stay (LOS) of critically ill patients and to investigate whether they are receiving prompt treatment through Interhospital Transfer (IHT).MethodsThis study analyzed 968 critically ill patients transferred to the ED of the study site in 2019. Machine learning based prediction models were built to predict the ED LOS dichotomized as greater than 6 hours or less. Explanatory variables in patient characteristics, clinical characteristics, transfer-related characteristics, and ED characteristics were selected through univariate analyses.ResultsAmong the prediction models, the Logistic Regression (AUC 0.85) model showed the highest prediction performance, followed by Random Forest (AUC 0.83) and Naïve Bayes (AUC 0.83). The Logistic Regression model suggested that the need for emergency operation or angiography (OR 3.91, 95% CI=1.65–9.21), the need for Intensive Care Unit (ICU) admission (OR 3.84, 95% CI=2.53–5.83), fewer consultations (OR 3.57, 95% CI=2.84–4.49), a high triage level (OR 2.27, 95% CI=1.43–3.59), and fewer diagnoses (OR 1.32, 95% CI=1.09–1.61) coincided with a higher likelihood of 6-hour-or-less stays in the ED. Furthermore, an interhospital transfer handoff led to significantly shorter ED LOS among the patients who needed emergency operation or angiography, or ICU admission, or had a high triage level.ConclusionsThe results of this study suggest that patients prioritized in emergency treatment receive prompt intervention and leave the ED in time. Also, having a proper interhospital transfer handoff before IHT is crucial to provide efficient care and avoid unnecessarily longer stay in ED.
Modulation of Cortical Inhibition by Lovastatin in Neurofibromatosis Type 1: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial
Authors: Bernardino Ines , Dionísio Ana , Castelo-Branco Miguel
Published: January 2022

Neurofibromatosis type 1 (NF1) is associated with GABAergic dysfunction which has been suggested as the underlying cause of cognitive impairments. Previous intervention trials investigated the statins’ effects using cognitive outcome measures. However, available outcome measures have led to inconclusive results and there is a need to identify other options. Here, we aimed at investigating alternative outcome measures in a feasibility trial targeting cortical inhibition mechanisms known to be altered in NF1. We explored the neurochemical and physiological changes elicited by lovastatin, with magnetic resonance spectroscopy and transcranial magnetic stimulation (TMS). Fifteen NF1 adults participated in this randomized, triple-blind, placebo-controlled crossover trial (Clinicaltrials.gov NCT03826940) composed by one baseline and two reassessment visits after lovastatin/placebo intake (60mg/day, 3-days). Motor cortex GABA+ and Glx concentrations were measured using HERMES and PRESS sequences, respectively. Cortical inhibition was investigated by paired-pulse, input-output curve and cortical silent period (CSP) TMS protocols. CSP ratios were significantly increased by lovastatin (relative: p=0.027; absolute: p=0.034) but not by placebo. CSP durations showed a negative correlation with LICI 50ms amplitude ratio. Lovastatin was able to modulate cortical inhibition in NF1, as assessed by TMS CSP ratios, highlighting the potential of this outcome measure to be considered in future large-scale studies.
Gene Function Prediction in Five Model Eukaryotes Exclusively Based on Gene Relative Location Through Machine Learning
Authors: Obregón Flavio Pazos , Silvera Diego , Soto Pablo , Yankilevich Patricio , Guerberoff Gustavo , Cantera Rafael
Published: January 2022

The function of most genes is unknown. The best results in automated function prediction are obtained with machine learning-based methods that combine multiple data sources, typically sequence derived features, protein structure and interaction data. Even though there is ample evidence showing that a gene’s function is not independent of its location, the few available examples of gene function prediction based on gene location rely on sequence identity between genes of different organisms and are thus subjected to the limitations of the relationship between sequence and function. Here we predict thousands of gene functions in five model eukaryotes (Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Homo sapiens) using machine learning models exclusively trained with features derived from the location of genes in the genomes to which they belong. Our aim was not to obtain the best performing method to automated function prediction but to explore the extent to which a gene's location can predict its function in eukaryotes. We found that our models outperform BLAST when predicting terms from Biological Process and Cellular Component Ontologies, showing that, at least in some cases, gene location alone can be more useful than sequence to infer gene function.
Postmastectomy radiotherapy after neoadjuvant chemotherapy in cT1-2N+ breast cancer patients: a single center experience and review of current literature
Authors: Luo Meng , Chen Huihui , Deng Hao , Jin Yao , Wang Gui , Zhang Kun , Ma Hong , Chen Yiding , Zhang Suzhan , Zhou Jiaojiao
Published: January 2022

PurposePostmastectomy radiotherapy (PMRT) after NAC in breast cancer patients with initial clinical stage cT1−2N+, especially for those who achieved ypT1−2N0, is still controversial. This study was to evaluate the survival prognosis of cT1−2N+ patients after NAC with or without PMRT, and to discuss the selection of patients who may omit PMRT.Patients and MethodsFrom January 2005 to December 2017, 3055 female breast cancer patients underwent mastectomy in our medical center, among whom 215 patients of cT1−2N+ stage, receiving neoadjuvant chemotherapy (NAC) with or without PMRT were finally analyzed. The median follow-up duration was 72.6 months. The primary endpoint was overall survival, and the secondary endpoint was disease-free survival. Comparison was conducted between PMRT and non-PMRT subgroups.ResultsOf the 215 eligible patients, 35.8% (77/215) cT1−2N+ patients achieved ypT0−2N0 after NAC while 64.2% (138/215) of the patients remained nodal positive (ypT0−2N+). The 5-year DFS of ypT0−2N0 non-PMRT was 79.5% (95% confidence interval [CI] 63.4-95.6%). No statistically significant difference was observed between the ypT0−2N0 PMRT and non-PMRT subgroups for the 5-year DFS (78.5% vs 79.5%, p = 0.673) and OS (88.8% vs 90.8%, p = 0.721). The 5-years DFS didn’t obviously differ between the ypT0−2N0 non-PMRT subgroup and cT1−2N0 subgroup (79.5% vs 93.3%, p = 0.070). By using Cox regression model in multivariate analyses of prognosis in ypT0−2N+ PMRT subgroup, HER2 overexpression and triple-negative breast cancer were significantly poor predictors of DFS and OS, while ypN stage was significant independent predictors of OS.ConclusionAn excellent response to NAC (ypT0−2N0) indicates a sufficiently favorable prognosis, and PMRT might be omitted for cT1−2N+ breast cancer patients with ypT0−2N0 after NAC.
Rostral Hypothalamic Differentiation With Minimal Exogenous Signals in Human Naive Induced Pluripotent Stem Cells
Authors: Ozaki Hajime , Suga Hidetaka , Sakakibara Mayu , Soen Mika , Miyake Natsuki , Miwata Tsutomu , Taga Shiori , Nagai Takashi , Kano Mayuko , Mitsumoto Kazuki , Miyata Takashi , Kobayashi Tomoko , Sugiyama Mariko , Onoue Takeshi , Takagi Hiroshi , Hagiwara Daisuke , Iwama Shintaro , Banno Ryoichi , Iguchi Genzo , Takahashi Yutaka , Muguruma Keiko , Inoue Haruhisa , Arima Hiroshi
Published: January 2022

Familial neurohypophyseal diabetes insipidus (FNDI) is a degenerative disease of vasopressin (AVP) neurons. Studies in mouse in vivo models indicate that accumulation of mutant AVP prehormone is associated with FNDI pathology. However, studying human FNDI pathology in vivo is technically challenging. Therefore, an in vitro human model needs to be developed. When exogenous signals are minimized in the early phase of differentiation in vitro, mouse embryonic stem cells (ESCs) differentiate into AVP neurons, whereas human ESCs/induced pluripotent stem cells (iPSCs) die. Human ES/iPSCs are generally more similar to mouse epiblast stem cells compared to mouse ESCs, which are termed as primed and naive, respectively. In this study, we converted human FNDI-specific iPSCs from primed to naive cells, and found improved cell survival under minimal exogenous signals and differentiation into rostral hypothalamic organoids. Overall, this method provides a simple and straightforward differentiation direction, which may improve the efficiency of hypothalamic differentiation.
Evaluation of Ocular Surface Epithelial and Stromal Thicknesses in Psoriasis Using Anterior Segment Optical Coherence Tomography
Authors: Ersan Ismail , Kılıc Sevilay , Isık Selda
Published: January 2022

Purpose: To evaluate the epithelial and stromal thicknesses of conjunctiva and cornea in psoriatic patients with anterior segment optical coherence tomography (AS-OCT),Methods: In this cross-sectional study, 61 patients with psoriasis and 42 age-matched, healthy individuals were enrolled. The epithelial and stromal thicknesses of both inferotemporal bulbar conjunctiva and central cornea were measured using AS-OCT. Results: Both the Tear break-up time and Schirmer-1 test values were significantly lower in the psoriasis group compared with the controls (p<0.05). The epithelial thickness of conjunctiva and cornea did not differ between psoriasis and control groups. (p>0.05) The central corneal stroma was significantly thicker in the psoriasis group (p=0.04). PASI was positively correlated with the thickness of central cornea stroma (r=0.442, p=0.006) in the nail psoriasis group. Conclusions: Psoriasis is not associated with altered epithelial thicknesses of the cornea and conjunctiva. It is accompanied by the stromal thickening of the cornea without conjunctival stromal involvement.
circ_0035277 Promotes Gastric Cancer Proliferation and Metastasis via miR-576-3p/LIN28B Axis
Authors: Wang Xiaoyan , He Rong , Wang Yan , Liu Yunyun , Wang Yuxin , Chen Dandan , Fan Yu
Published: January 2022

Circular RNAs (circRNAs) regulate biological processes of human tumours. Gastric cancer is a prevalent disease that presents tumours with high metastasis. This study aimed to understand regulatory function and mechanism of circ_0035277 in gastric cancer development. circ_0035277 level in tissues and cells was assessed using RT-qPCR assay. Function of circ_0035277 was evaluated via CCK-8, colony formation and Transwell assays. Location of circ_0035277 was verified with FISH assay. Potential mechanism of circ_0035277 was examined using bioinformatics and luciferase reporter assays. BALB/c nude mice were utilised to construct the gastric cancer metastasis model with subcutaneous injection. Haematoxylin–eosin staining was performed to measure visible tumour nodules in lung tissues. Results showed that circ_0035277 is significantly up-regulated in tissues and cell lines of gastric cancer, accelerates the deterioration of gastric cancer, is significantly located in the cytoplasm and serves as a sponge to participate in gastric cancer by targeting miR-576-3p. Furthermore, lin-28 homolog B (LIN28B) was a direct target of miR-576-3p and reversed the role of circ_0035277/miR-576-3p on gastric cancer metastasis. In vivo studies have shown that knockdown of circ_0035277 suppresses gastric cancer metastasis. Overall, circ_0035277 accelerated gastric cancer progression and metastasis by regulating miR-576-3p/LIN28B axis. These findings can provide a potential target for the treatment of gastric cancer.
Comparative Life Cycle Assessment of Safety Shoes Toe Caps Manufacturing Processes
Authors: Bianchi Iacopo , Forcellese Archimede , Simoncini Michela , Vita Alessio , Castorani Vincenzo , Cafagna Damiana , Buccoliero Giuseppe
Published: January 2022

Toe caps are fundamental components of safety footwear used to prevent injuries which can be caused by falling objects. They can be realized by exploiting different materials (metal, composites and plastics) and manufacturing processes (stamping, injection molding, compression molding, etc.). However, they have always to fulfill the stringent requirements of safety regulations. In addition, in order to guarantee an ergonomic use, they must be as light as possible. It is estimated that at least 300 million pairs of safety footwear, with 600 million of toe caps, end up in landfill or are incinerated every year. This huge amount of wastes generates a relevant environmental impact, mainly attributable to toe caps manufacturing. In this context, it is important to develop new solutions which minimize the environmental impacts of toe caps manufacturing. Among others, the reuse of carbon fiber prepreg scraps has been recognized as a valid method to produce effective toe caps. In this paper, a detailed analysis of the environmental impacts associated to toe caps realized with reclaimed prepreg scraps has been conducted exploiting the Life Cycle Assessment methodology. The results have been compared to those obtained by analyzing toe caps realized in steel, aluminum, polycarbonate and glass fiber composite. Results demonstrate that the reclaim process for carbon fiber prepreg scraps can be a valid circular economy model to produce more sustainable toe caps for safety footwear.
Tracing the Origins of Glioblastoma by Investigating the Role of Gliogenic and Related Neurogenic Genes/Signaling Pathways in GBM Development: A Systematic Review
Authors: Shafi Ovais , Siddiqui Ghazia
Published: January 2022

Background: Glioblastoma is one of the most aggressive tumors. The etiology and the factors determining its onset are not yet entirely known. This study investigates the origins of GBM and for this purpose it focuses primarily on developmental gliogenic processes. It also focuses on impact of the related neurogenic developmental processes in glioblastoma oncogenesis. It also addresses why glial cells are at more risk of tumor development compared to neurons.Methods:Databases including PubMed, MEDLINE and Google Scholar were searched for published articles without any date restrictions, involving glioblastoma, gliogenesis, neurogenesis, stemness, neural stem cells, gliogenic signaling and pathways, neurogenic signaling and pathways, astrocytogenic genes.Results:The origin of GBM is dependent on dysregulation in multiple genes and pathways that accumulatively converge the cells towards oncogenesis. There are multiple layers of steps in glioblastoma oncogenesis including the failure of cell fate specific genes to keep the cells differentiated in their specific cell type such as p300, BMP, HOPX, NRSF/REST and others. There are genes and signaling pathways that are involved in differentiation and also contribute to GBM such as FGFR3, JAK-STAT, hey1 and others. The genes that contribute to differentiation processes but also contribute to stemness in GBM include notch, Sox9, Sox4, c-myc gene overrides p300 and then GFAP, leading to upregulation of nestin, SHH, NF-κB and others. GBM mutations pathologically impact the cell circuitry such as the interaction between Sox2 and JAK-STAT pathway, resulting in GBM development and progression. Conclusion: Glioblastoma originates when the gene expression of key gliogenic genes and signaling pathways become dysregulated. This study identifies key gliogenic genes having the ability to control oncogenesis in glioblastoma cells, including p300, BMP, PAX6, HOPX, NRSF/REST, LIF, TGF beta. It also identifies key neurogenic genes having the ability to control oncogenesis including PAX6, neurogenins including Ngn1, NeuroD1, NeuroD4, Numb, NKX6-1 Ebf, Myt1, ASCL1 and others. This study also postulates how aging contributes to the onset of glioblastoma by dysregulating the gene expression of NF-κB, REST/NRSF, ERK, AKT, EGFR and others.
A Green Strategy to Produce Potential Substitute Resource for Bear Bile Using Engineered Saccharomyces Cerevisiae
Authors: Jin Lina , Yang Li , Zhao Shujuan , Wang Zhengtao
Published: January 2022

BackgroundBear bile powder is a precious natural material characterized by high content of tauroursodeoxycholic acid (TUDCA) at a ratio of 1.00–1.50 to taurochenodeoxycholic acid (TCDCA).ResultsIn this study, we use the crude enzymes from engineered Saccharomyces cerevisiae to directional convert TCDCA from chicken bile powder to TUDCA at the committed ratio in vitro. This S. cerevisiae strain was modified with heterologous 7α-hydroxysteroid dehydrogenase (7α-HSDH) and 7β-hydroxysteroid dehydrogenase (7β-HSDH) genes. S. cerevisiae host and HSDH gene combinatorial optimization and response surface methodology was applied to get the best engineered strain and the optimal biotransformation condition, respectively, under which 10.99 ± 0.16 g/L of powder products containing 36.73±6.68 % of TUDCA and 28.22±6.05 % of TCDCA were obtained using 12.00 g/L of chicken bile powder as substrate.Conclusion﻿This study provides a healthy and environmentally friendly way to produce potential alternative resource for bear bile powder from cheap and readily available chicken bile powder, and also gives a reference for the green manufacturing of other rare and endangered animal-derived valuable resource.
Strategies for Prevention of COVID-19 Transmission in Hospitals: a Nationwide Survey of Controversial Issues Related to Infection Control and Prevention in Korea
Authors: Jang Wooyoung , Kim Bongyoung , Kim Eu Suk , Song Kyoung-Ho , Moon Song Mi , Lee Myung Jin , Park Ji Young , Kim Ji-Yeon , Shin Myoung Jin , Lee Hyunju , Kim Hong Bin
Published: January 2022

Background: Infection-control measures against the coronavirus disease 2019 (COVID-19) within a hospital are often based on expert experience and intuition due to the lack of clear guidelines. This study aimed to survey the current strategies for the prevention of the spread of COVID-19 in medical institutions.Methods: In a systematic review of national-level guidelines, 13 key topics were selected. Six hospitals were provided an open survey between August 11 and 25, 2020, to assess their responses to these topics. Using these data, an online questionnaire was developed and sent to the infection-control teams of 46 hospitals in South Korea. The survey was conducted between January 31, 2021, and February 20, 2021.Results: All 46 hospitals responded to the survey. All hospitals operated screening clinics, while 89.1% (41/46) allowed symptomatic patients without COVID-19-associated symptoms to visit the general outpatient clinics. Most hospitals (87.2%; 34/39) conducted polymerase chain reaction (PCR) tests for all hospitalised patients. Moreover, 35 (76.1%) hospitals had preemptive isolation policies for hospitalised patients, of which 97.1% (34/35) released patients from isolation after a single negative PCR test. Most hospitals (76.9%; 20/26) allowed shared-room accommodation for patients who met the national criteria for release from isolation but showed positive PCR results with cycle threshold values above a certain threshold (34.6%; 9/26) or after a certain period that satisfied the national criteria (26.9%; 7/26). Conclusions: Various guidelines were being applied by each medical institution, but an explicit set of national guidelines to support these guidelines was unavailable.
Deep Water Pathways In The North Pacific Ocean Revealed By Lagrangian Particle Tracking
Authors: Kawasaki Takao , Matsumura Yoshimasa , Hasumi Hiroyasu
Published: January 2022

Lagrangian particle tracking experiments are conducted to investigate the pathways of deep water in the North Pacific Ocean. The flow field is taken from a state-of-the-art deep circulation simulation. An unprecedented number of particles are tracked to quantify the volume transport and residence time. Half of the North Pacific deep water returns to the Southern Ocean, and its principal pathway is along the western boundary current in the Southwest Pacific Basin in the deep layer. About 30 % is exported to the Indian Ocean after upwelling to the shallow layer in the western North Pacific Ocean. The rest is transported to the Arctic Ocean through the Bering Strait or evaporates within the Pacific Ocean. Upwelling of deep water is confined in the western North Pacific Ocean owing to the strong vertical mixing. The mean residence time of deep water in the North Pacific Ocean is estimated to be several hundred years, which is considerably shorter than the conventional understandings of the deep Pacific Ocean circulation.
Microtransplantation Improves the Outcome of Older Patients With Newly Diagnosed Acute Myeloid Leukaemia: a Single-centre Study With Long-term Follow-up
Authors: Liu Juan , Huang Xiao-mei , Zhao Si-yuan , Yang Ya-kun , Qu Yuan-yuan , Zhao Jin-na , Lv Pan-pan , Yang Chao , Sun Wan-jun
Published: January 2022

Purpose: This retrospective single-centre study was to validate the efficacy and safety of microtransplantation (or micro-stem cell transplantation, MST) in the treatment of older patients with acute myeloid leukemia (AML).Methods: MST combines chemotherapy and human leukocyte antigen (HLA)-mismatched peripheral blood stem cell infusion without graft-versus-host disease (GVHD) prophylaxis. In total, 26 newly diagnosed AML patients were enrolled in our study from April 2008 to April 2018. The deadline date of follow-up was December 31, 2019. All of them received MST. Patients were divided into 2 age groups: 60~70 years (n=17) and >70 years (n=9). The outcomes of complete remission (CR) rate, overall survival (OS), leukemia free survival (LFS), hematopoietic recovery time, and treatment related toxicities were analyzed and summarized in this study.Results: 10 patients were still alive with complete remission (CR) at the deadline date, and the median overall survival (OS) was 64 months (range, 21-135 months). The CR, relapse and nonrelapse mortality rates were 84.6%, 38.5% and 30%, respectively. Both OS (p < 0.0001) and leukaemia free survival (LFS) (p < 0.0001) were significantly higher in the younger group than in the older group. The median times of neutrophil and platelet recovery were 12 days and 14 days, respectively. Conclusions: These data showed that MST could be an alternative treatment for older AML patients.
Monthly Average Rainfall Forecasting Based On An Adaptive Neuro-Fuzzy Inference System in Upper Brahmani Basin, Odisha, India
Authors: Rao M.Uma Maheswar , Patra Kanhu Charan , Sasmal Suvendu Kumar
Published: January 2022

Floods disrupt human activities, resulting in the loss of lives and property of a region. Excessive rainfall is one of the reasons for flooding, especially in the downstream areas of a catchment. Because of its complexity, understanding and forecasting rainfall is incredibly a challenge. This study investigates the use of an Adaptive Neuro-Fuzzy Inference System (ANFIS) in predicting rainfall using several surface weather parameters as predictors. An ANFIS model is developed for forecasting rainfall over the Upper Brahmani Basin by using 30 years of climate data. A hybrid model with six membership functions gives the best forecast for an area. The suggested method blends neural network learning capabilities with language representations of fuzzy systems that are transparent. The application of ANFIS is to the upper Brahmani river basin is tried for the first time. The ANFIS model with various input structures and membership functions has been built, trained, and tested to evaluate the capability of the model. Statistical performance indices are used to evaluate the performance. Using the developed model, forecast is done for year 2021 – 2030.
Comprehensive Analysis on the Hydrologic Alteration and Causes of River Runoff in Min River of the Yangtze River, China
Authors: Guo Wenxian , Zhou Haotong , Jiao Xuyang , Zhu Yongwei , Wang Hongxiang
Published: January 2022

The construction of water conservancy projects has changed the hydrological situation of rivers and has an essential impact on the river ecosystem. The influence modes of different factors on runoff alteration are discussed to improve the development and utilization of water resources and promote ecological benefits. The ecological, hydrological index change range method (IHA-RVA) and hydrological alteration degree method were comprehensively used to evaluate Min River's hydrological situation. Based on six budyko hypothesis formulas, the contribution rates of climate change and human activities to runoff change are quantitatively analyzed. The study showed that the runoff of Min River basin showed a significant decreasing trend from 1960 to 2019 and a sudden alteration around 1993; The overall alteration in runoff conditions was 45% moderate, and the overall alteration in precipitation was 37% moderate; Precipitation and potential evapotranspiration also showed a decreasing trend within the same period, but the overall trend was not significant; The contribution of climate alteration to runoff alteration is 30.2%, and the contribution of human activities to runoff alteration is 69.8%, human activities are the dominant factor affecting the alteration of runoff situation in Min River basin.
Is SARS-CoV-2 Omicron (B.1.1.529) variant causing different symptoms?
Authors: Lippi Giuseppe , Mattiuzzi Camilla , Henry Brandon M.
Published: January 2022

Background: Since preliminary evidence suggests that the new SARS-CoV-2 Omicron (B.1.1.529) variant may cause different symptoms and trigger outbreaks associated with less severe illness compared to previous strains, we conducted and infodemic analysis to verify these suppositions.Methods: We searched Google Trends using the most frequent COVID-19 symptoms, with “United Kingdom” country option and search periods “20-26 December 2020” (predominance of Alpha variant) and “19-25 December 2021” (Omicron prevalence >80%).Results: Seven symptoms (i.e., conjunctivitis, chills, cough, aches, fever, nausea and sore throat) appeared to be more searched in 2021 compared to 2020 (i.e., >15% increase), five symptoms (i.e., anosmia, tiredness, ageusia, sneezing and shortness of breath) were found to be less searched in 2021 compared to 2020 (i.e., >15% decrease), whilst the number of Google searches for headache, diarrhea and runny nose were almost comparable between the two periods (i.e., <15% variation).Conclusion: Actual predominance of Omicron (B.1.1.529) variant in UK is associated with higher number of Google searches for mild symptoms (conjunctivitis, chills, cough, aches and fever), accompanied by considerable lower interest for a severe clinical sign like shortness of breath, which characterizes lower respiratory tract infection.
Evaluation of the Anticonvulsant Activities of Gastrodia Elata Bl.- Acorus Tatarinowii Decoction on Experimentally Induced Seizures in Mice
Authors: He Xirui , Yang Yan , Yuan Xufang , Sun Yin
Published: January 2022

Epilepsy is a serious public health problem in the world. At present, the effect of drug treatment of epilepsy is are not satisfactory. Medicinal plants as pharmaceuticals and for healthcare treatments in the management of epilepsy in China for many centuries. Especially, Gastrodia elata Bl.-Acorus tatarinowii, as a classic and important herb pairs in folk medicine, has been used in folk medicine to control seizures. However, the animal experiment data of its anticonvulsant effect is limited in the literature. The objective of this study was to mainly analyze the anticonvulsant activity of Gastrodia elata-Acorus tatarinowii (GEAT) decoction in maximal electroshock (MES), pentylenetetrazole (PTZ) and trimercaptopropionic acid (3-MP) induced seizures in mice, providing scientific basis for the treatment of convulsive disorders in traditional medicine. In addition, the improvement effect were examined on seizure severity, anxiety, cognitive dysfunction, inflammation and oxidative stress in PTZ kindled mice. The results showed that GEAT decoction dose-dependently protected mice against MES, 3-MP and PTZ induced acute seizures. Meanwhile, GEAT decoction ameliorated seizure severity, decreased the accumulation of inflammatory mediators TNF-α, IL-1β, and IL-6, mitigated oxidative stress, as well as alleviated anxious-like behavior and cognitive deficits in PTZ-kindled mice. Our data evidenced that the anticonvulsant properties attributed to GEAT decoction as adjunctive therapy for epileptic patients in folk medicine.
How Large Fraction of A Population Must be Vaccinated before A Disease is Controlled?
Authors: Halamicek Robin , Schubert Dirk W , Nilsson Fritjof
Published: January 2022

The ongoing Covid-19 pandemic has already caused more than 5 million casualties despite hard restrictions and relatively high vaccine coverage in many countries. The crucial question is therefore, how large vaccination rate and how severe restrictions are required to terminate the spread of the decease, assuming that the vaccine efficiency and the basic reproduction ratio (R0) are known? To answer this question, a simple mathematical equation was developed to visualize the required vaccination level as function of vaccine efficiency, restriction efficiency and basic reproduction ratio (R0). In addition to the modelling study, Covid-19 data from Europe was collected during 19/11-26/11 (2021) to assess the relation between vaccination rate and incidence. The analysis indicates that a vaccination rate of ~92% (2 doses) is currently required to stop Delta (B.1.617.2) without severe restrictions, using the vaccines that are most common in Europe today. A third vaccine dose, improved vaccines, higher vaccination rates and/or stronger restrictions will be required to force Omicron (B.1.1.529) to expire without infecting a large fraction of the population.