bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive Values of the Selected Inflammatory Index in the Progression of Colon Cancer Patients
Authors: Huang Li , Hu Zuojian , Luo Ruixian , Li Hailan , Yang Ziji , Mo Zhuning
Published: October 2021

Background: Ample evidence has revealed that the lymphocyte-to-monocyte ratio (LMR), albumin-to-globulin ratio (AGR) and mean platelet volume (MPV) are cancer-related inflammatory markers. The present study aimed to assess a better diagnostic marker for the progression of colon cancer. Methods: This retrospective study enrolled 251 patients with colon cancer, 171 patients with benign colon diseases, and 187 healthy control subjects from January 2012 to September 2020. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to determine the diagnostic values of the selected inflammatory index.Results: The levels of LMR, AGR and MPV were decreased in the colon cancer group compared with the healthy control and benign colon disease groups. The LMR, AGR and MPV were all correlated with tumor size. Moreover, LMR and AGR was associated with lymph node metastasis and clinical stage, AGR was related to distant metastasis. Both the LMR (p = 0.030) and AGR (p = 0.005) were negatively correlated with the concentration of carcinoembryonic antigen (CEA). The AUC value of MPV combined with CEA had a good diagnostic ability for distinguishing controls from colon cancer cases (AUC = 0.950) and patients with benign colon diseases (AUC = 0.886). Meanwhile, the combination of LMR or AGR with CEA could enhance the diagnostic efficacy (AUC; 0.746 for LMR + CEA, 0.737 for AGR + CEA) of detecting colon cancer from benign colon diseases. Conclusions: CEA combined with the selected inflammatory index may be used as better blood-based biomarkers in the progression of colon cancer patients.
Identifying Key Factors Associated with Subscapularis Tendon Tears and Developing a Risk Prediction Model to Assist Diagnosis
Authors: xu Wennan , wang Fei , xue Qingyun
Published: October 2021

Background: Subscapularis (SSC) tendon tears can cause pain and restricted motion of the shoulder, but accurate diagnosis of this lesion on magnetic resonance imaging (MRI) is challenging, especially in small and partial tears. There are no studies that have established a method to reliably assess the risk of subscapularis tendon tears.Methods: Data on 460 patients who received shoulder arthroscopic surgery with preoperative shoulder MRI were collected retrospectively. Of these, patients with SSC tendon tears were defined as the SSC tear group, and patients with intact subscapularis tendon were enrolled in the non-SSC tear group. Logistic regression analysis was used to identify the risk factors of SSC tendon tears which were then incorporated into the nomogram. Results: Among 22 candidate factors, five independent factors including coracohumeral distance CHD (oblique sagittal) (OR, 0.75; 95%CI, [0.67-0.84]), fluid accumulation (Y-face) (OR, 2.29; 95%CI, [1.20-4.38]), long head of biceps tendon (LHB) dislocation/subluxation (OR, 3.62; 95%CI, [1.96-6.68]), number of posterosuperior (PS) rotator cuff tears (OR, 5.36; 95%CI, [3.12-9.22]), and MRI diagnosis (OR, 1.88; 95%CI, [1.06-3.32]) were identified as key predictors associated with subscapularis tendon tears. Incorporating these predictors, the nomogram achieved a good C index with a good agreement on the risk estimation of calibration plots. Higher total points of the nomogram were associated with a greater risk of subscapularis tendon tears. Conclusion: The diagnostic accuracy of conventional 3.0-T MRI for SSC tendon tears was insufficient. Our study revealed critical predictors associated with subscapularis tendon tears. When evaluating the severity of subscapularis tendon injury, more attention should be paid to these tear-related factors. We developed and validated s satisfactory prediction model to improve the diagnostic performance of MRI which was convenient for clinicians to reach a consensus on risk assessment and identify the SSC tendon tears.
Influence of Cusp External Magnetic Field on Deposition Rate of Two-electrode TIG Welding
Authors: Liu Liming , Zhu Yanli , Liu Runtao
Published: October 2021

Experiments have been conducted to investigate the influence of the cusp external magnetic field (EMF) on deposition rate of two-electrode tungsten insert gas (T-TIG) welding. T-TIG arc parameters such as arc shape, arc voltage, arc pressure and arc plasma information were acquired respectively. Results showed compared to TIG, a higher welding current could be allowed for T-TIG, due to its low arc pressure characteristic. Under the effect of the cusp EMF, the arc shape was compressed along x-axis of T-TIG, while elongated along y-axis of T-TIG. Besides, the peak arc pressure of T-TIG was not significantly increased by the cusp EMF. Moreover, with the action of the cusp EMF, the maximum values of the electron temperature (Te) and electron density (Ne) of T-TIG were not significantly increased, but along y-axis, the increments of the two parameters were gradually increased and their distributions were widened. Therefore, more arc energy was allocated on y-axis of T-TIG by the cusp EMF, which could improve the preheating and the melting of the filler wire along y-axis, so the deposition rate of T-TIG could be increased by 17.6% under the effect of the cusp EMF.
WITHDRAWN: Fuzzy reliability analysis based on support vector machine
Authors: Nie xiao bo , Li Haibin , Chen Hongxia , Pang Ruying , Sun Honghua
Published: October 2021

For a structure with implicit performance function structure and less sample data, it is difficult to obtain accurate probability distribution parameters by traditional statistical analysis methods. To address the issue, the probability distribution parameters of samples are often regarded as fuzzy numbers. In this paper, a novel fuzzy reliability analysis method based on support vector machine is proposed. Firstly, the fuzzy variable is converted into an equivalent random variable, and the equivalent mean and equivalent standard deviation are calculated. Secondly, the support vector regression machine with excellent small sample learning ability is used to train the sample data. Subsequently, and the performance function is approximated. Finally, the Monte Carlo method is used to obtain fuzzy reliability. Numerical examples are investigated to demonstrate the effectiveness of the proposed method, which provides a feasible way for fuzzy reliability analysis problems of small sample data.
An Efficient Approach For the Nodal Water Demand Estimation in Large-Scale Water Distribution Systems
Authors: Chu Shipeng , Zhang Tuqiao , Zhou Xinhong , Yu Tingchao , Shao Yu
Published: October 2021

Real-time modeling of the water distribution system (WDS) is a critical step for the control and operation of such systems. The nodal water demand as the most important time-varying parameter must be estimated in real-time. The computational burden of nodal water demand estimation is intensive, leading to inefficiency for the modeling of the large-scale network. The Jacobian matrix computation and Hessian matrix inversion are the processes that dominate the main computation time. To address this problem, an approach to shorten the computational time for the real-time demand estimation in the large-scale network is proposed. The approach can efficiently compute the Jacobian matrix based on solving a system of linear equations, and a Hessian matrix inversion method based on matrix partition and Iterative Woodbury-Matrix-Identity Formula is proposed. The developed approach is applied to a large-scale network, of which the number of nodal water demand is 12523, and the number of measurements ranging from 10 to 2000. Results show that the time consumptions of both Jacobian computation and Hessian matrix inversion are significantly shortened compared with the existing approach.
Far from boring: a new Grenvillian perspective on Mesoproterozoic tectonics
Authors: Gervais Félix , Beaudry Alexandre , Kavanagh-Lepage Charles , Moukhsil Abdelali
Published: October 2021

As determining when plate tectonics began on Earth is a highly debated subject, it is crucial to understand the “boring billion” (1.8 to 0.8 billion years ago), a period of tectonic quiescence inferred from proxies, such as the average chemical composition of the mineral zircon on Earth and the isotopic composition of seawater derived from marine rocks. Yet this period saw the construction of what may have been the biggest mountain belt that ever existed, the remnants of which are found in the Grenville Orogen of eastern North-America. This contribution first exposes a compilation of multidisciplinary geological datasets and new geochemical data from igneous suites emplaced during the Grenvillian Orogeny that are incompatible with the current tectonic paradigm. We then present a completely revised model for Grenvillian tectonics. In contrast with the actual Laurentian-centred paradigm, our model involves the construction of a newly revealed continent by amalgamation of volcanic arcs far away from Laurentia (the craton forming the core of actual North-America) and their collision 60 millions year later than the currently accepted timing. This new model resolves the longstanding contradiction between tectonic proxies and geological record and invalidates the view considering the Mesoproterozoic as a tectonically quiet Era.
Fisetin attenuates Renal Ischemia/Reperfusion Injury by improving mitochondrial quality, reducing apoptosis and oxidative stress
Authors: Prem Priyanka N , Kurian Gino A
Published: October 2021

Purpose
Renal ischemic reperfusion (IR) injury is one of the major source of mortality and morbidity associated with acute kidney injury (AKI). Several flavonoids have shown to be renal protective against many nephrotoxic agents causing AKI. Fisetin, a promising flavonoid, is effective in the management of septic AKI, expected to ameliorate renal IR injury. Present study aim to generate evidence for fisetin mediated renal protection against IR injury
Methodology:
Male wistar rats of 200-250 g subjected to IR protocol by performing bilateral clamping for 45 minutes and reperfusion for 24 hours. Fisetin administrated 30 minutes ( 20 mg/kg b.wt, ip) before the surgery. Renal injury was evaluated by measuring the biomarkers in plasma, examining the ultrastructure of kidney and analyzing the apoptotic changes. Oxidative stress, antioxidant levels and mitochondrial function were analysed in the renal tissue.
Results
Fisetin administration significantly reduced the renal damages associated with IR, by improving estimated glomerular filtration rate (eGFR: IR-0.35 ml/min, F_IR-9.03 ml/min), reducing plasma creatinine level (IR-2.2 mg/dl, F_IR-0.92 mg/dl) and lowering urinary albumin/creatinine ratio (IR- 6.09 F_IR-2.16), caspase activity, decreased DNA fragmentation and reduced tubular injury score (IR- 11 F_IR-6.5). At cellular level, fisetin significantly reduced renal oxidative stress and augmented the antioxidant levels. Fisetin found to preserve mitochondrial electron transport chain activities and improved the ATP producing capacity in the renal tissue upon IR injury.
Conclusion
fisetin pre-treatment attenuate renal IR injury by improving the renal function, reducing the renal injury mediated by apoptosis, reducing free radical release, and augmenting mitochondrial function.
Enterovirus 71 structural viral protein 1 promotes autophagy by inducing an m6A-mediated PMP22 overexpression in mouse Schwann cells
Authors: Liu Guangming , Zhu Danping , Hu Dandan , Li Suyun , Peng Qiuyan , Li Peiqing , Yang Sida
Published: October 2021

Objective

Enterovirus 71 (EV71), one of the enteroviruses responsible for the hand, foot and mouth disease (HFMD), can cause severe neurologic diseases such as brainstem encephalitis and demyelination. The molecular mechanism of demyelination is still not fully understood. This study aims to investigate the mechanism of how the EV71 structural viral protein 1, VP1 can act on host cellular pathways in mouse Schwann cells.
Methods

An EV71 VP1-expressing vector was generated and transfected into mouse Schwann cells (MSCs). Selective mRNA methylation inhibitor (DAA) was employed to identify key members of m6A pathway that are targeted by VP1. To investigate the role of METTL14 and YTHDF1 in PMP22 expression, small interfering RNA against METTL14 and YTHDF1 was employed to knockdown the METTL14 and YTHDF1 expression in MSCs. Real-time PCR and Western blot analysis were performed to determine the expression of PMP22 and m6A modification-associated proteins.
Results

Our results demonstrated VP1 upregulated m6A pathway by targeting METTL14 and YTHDF1. The expression of PMP22 was decreased by inhibiting the expression of METTL14 and YTHDF1.
Conclusions

VP1 upregulates m6A modification, which in turn causes the hypermethylation of PMP22 in MSCs, resulting in a higher level of PMP22. Ultimately, this VP1-induced PMP22 overexpression leads to MSC autophagy.
Identification of ATFs in Human Breast Cancer by Integrated Bioinformatic Analysis
Authors: Geng chenchen , Pu Qian , Tian Shuxu , Geng Wenwen , Wang Haiyan , Zhao Guanghui , Gao Haidong
Published: October 2021

Background: To obtain a thorough comprehension of the profile and prognosis of activating transcription factor (ATF) family members in breast cancer.Method: We searched Oncomine, GEPIA, cBioPortal, Kaplan-Meier plotter, and CancerSEA databases to assess expression level, prognostic value, and functions of ATFs in breast cancer. Results: In breast cancer, we found that the expression levels of genes like ATF1, ATF5, and ATF6, were higher than in normal tissues. While the expression levels of ATF3, ATF4, ATF7 were lower in the former than in the latter. Similarly, the ATFs protein expressions were consistent with this in the Human Protein Atlas database. High expressions of ATF2, ATF4, and ATF6-7 were associated with good relapse-free survival. Increased expressions of ATF4 and ATF7 had high overall survival. Conversely, the mRNA expression of ATF1 was negatively correlated with distant metastasis-free survival. Similarly, high expression of ATF2 had reduced post-progression survival. Conclusions: ATF1 was a target of potential therapeutic interest for breast cancer, and ATF4 and ATF6-7 were potential prognostic factors in evaluating breast cancer.
Effects of Steam Treated Rice Straw-Based Diet on the Physico-Chemical Properties of Goats Longissimus Muscle
Authors: Naeem Muhammad , Ali Sher , Rajput Nasir Ali , Bilal Muhammad , Wang Tian
Published: October 2021

The present study was carried out to investigate the effects of steam treated rice straw-based diets on, physico-chemical properties of longissimus muscle of goat. Goats were assigned to rice straw treated with steam at 15.5 kgf/cm2 for 120 Sec (STRS) and untreated rice (UTRS) straw-based diets. After 60 days all goats were slaughtered and 50 g of muscle longissimus dorsi (LD) was removed from left side of carcass for determination of meat quality and fatty acid profile. The results showed that the steam treated rice straw diet improved (P < 0.05) carcass yield and dressing % of goats as compared to untreated rice straw fed goats. Significantly higher protein and lower moisture was observed for meat of STRS group than UTRS, however the fat, ash contents, meat color and pH were not different between the groups. The TBARS values gradually increased in stored meat. The different diet did not affect the composition of fatty acids. Total saturated (∑SFA) monounsaturated fatty acids (∑MUFA) for UTRS and total polyunsaturated fatty acid (∑PUFA) for STRS group was higher (P > 0.05). It is concluded that the goats fed on treated straw diet (STRS) maintained carcass yield, dressing % and meat composition without negative impact on meat characteristics.
Development of a radiographic scoring system for new bone formation in gout
Authors: Son Chang-Nam , Cai Ken , Stewart Sarah , Ferrier John , Billington Karen , Tsai Yun-Jung Jack , Bardin Thomas , Horne Anne , Stamp Lisa K. , Doyle Anthony , Dalbeth Nicola
Published: October 2021

Background
Features of new bone formation (NBF) are common in tophaceous gout. The aim of this project was to develop a plain radiographic scoring system for NBF in gout.
Methods
Informed by a literature review, scoring systems were tested in 80 individual 1st and 5th metatarsophalangeal joints. Plain radiography scores were compared with computed tomography (CT) measurements of the same joints. The best-performing scoring system was then tested in paired sets of hand and foot radiographs obtained over two years from an additional 25 patients. Inter-reader reproducibility was assessed using intra-class correlation coefficients (ICC). NBF scores were correlated with plain radiographic erosion scores (using the gout-modified Sharp-van der Heijde system).
Results
Following a series of structured reviews of plain radiographs and scoring exercises, a semi-quantitative scoring system for sclerosis and spur was developed. In the individual joint analysis, the inter-observer ICC (95% CI) was 0.84 (0.76-0.89) for sclerosis and 0.81 (0.72-0.87) for spur. Plain radiographic sclerosis and spur scores correlated with CT measurements (R2 = 0.65-0.74, P < 0.001 for all analyses). For the hand and foot radiograph sets, the inter-observer ICC (95% CI) was 0.94 (0.90-0.98) for sclerosis score and 0.76 (0.65-0.84) for spur score. Sclerosis and spur scores correlated highly with plain radiographic erosion scores (R2 = 0.87 and 0.71 respectively), but not with change in erosion scores over two years (R2 = -0.04 – 0.15).
Conclusion
A semi-quantitative plain radiographic scoring method for assessment of NBF in gout is feasible, valid, and reproducible. This method may facilitate consistent measurement of NBF in gout.
VPS35 Protects Against TMEM230-Mutation-Induced Progressive Locomotor Deficits in Drosophila
Authors: Ma Chao , Wang Xiaobo , Smith Wanli W , Liu Zhaohui
Published: October 2021

BackgroundRecently, four Parkinson’s disease (PD)-linked mutations (Y92C, R141L, 184PGext*5 and 184Wext*5) in transmembrane protein 230 (TMEM230) were identified in PD patients, and these mutations have implications in protein trafficking and neurodegeneration. However, there is a lack of in vivo studies on the roles of PD-related variants of TMEM230 in PD pathogenesis.MethodsIn this study, we generated human wild-type (WT) and mutant TMEM230 (Y92C, R141L, 184PGext*5 and 184Wext*5) transgenic Drosophila using isoform Ⅱ cDNA. ResultsWe found that the expression of TMEM230 184PGext*5 in pan-neurons or dopaminergic neurons in Drosophila induced PD-like phenotypes, which included impaired locomotor ability, a shortened lifespan, reduced TH levels, and increased phosphorylated JNK and cleaved caspase-3 levels. Moreover, rotenone, a common pesticide, enhanced TMEM230-184PGext*5-induced PD-like phenotypes. In contrast, the overexpression of wild-type (WT) VPS35 rescued TMEM230-184PGext*5-induced PD-like phenotypes, while the knockdown of VPS35 by RNA interference (RNAi) or the expression of mutant VPS35 D620N worsened PD-like phenotypes. ConclusionThese results indicate that VPS35, as a downstream effector of TMEM230, plays a critical role in TMEM230-linked JNK/caspase-3 signalling pathways and that mutations in TMEM230 and VPS35 disrupt these pathways, resulting in dopaminergic neurodegeneration and PD-like phenotypes. These findings provide novel insight into the molecular mechanisms of mutant TME230- and VPS35-induced abnormalities underlying the pathogenesis of PD.
Signal Transduction in Light-Oxygen-Voltage Receptors Lacking the Active-Site Glutamine
Authors: Dietler Julia , Gelfert Renate , Kaiser Jennifer , Borin Veniamin , Renzl Christian , Pilsl Sebastian , Ranzani Américo Tavares , de Fuentes Andrés García , Gleichmann Tobias , Diensthuber Ralph , Weyand Michael , Mayer Günter , Schapiro Igor , Möglich Andreas
Published: October 2021

In nature as in biotechnology, light-oxygen-voltage (LOV) photoreceptors perceive blue light to elicit spatiotemporally defined cellular responses. Photon absorption drives thioadduct formation between a conserved cysteine and the flavin chromophore. An equally conserved, proximal glutamine processes the resultant flavin protonation into downstream hydrogen-bond rearrangements. Here, we report that this glutamine, long deemed essential, is generally dispensable. In its absence, several LOV receptors invariably retained productive, if often attenuated, signaling responses. Structures of a LOV paradigm at around 1 Å resolution revealed highly similar light-induced conformational changes, irrespective of whether the glutamine is present. Naturally occurring, glutamine-deficient LOV receptors likely serve as bona fide photoreceptors, as we showcase for a diguanylate cyclase. We propose that without the glutamine, water molecules transiently approach the chromophore and thus propagate flavin protonation downstream. Signaling without glutamine appears intrinsic to LOV receptors, which pertains to biotechnological applications and suggests evolutionary descendance from redox-active flavoproteins.
Lanthanide Tag in Search For Paramagnetically Induced Residual Dipolar Couplings in Small Molecules
Authors: Yassin Ali , Kantar Sally El , Obeid Sandy , Akoury Elias
Published: October 2021

The structure elucidation of molecules and determination of their characteristic interactions and thermodynamic processes have become routine measurements while using Nuclear Magnetic Resonance (NMR) spectroscopy as an indispensable technique. The theoretical description of NMR spectroscopy and treatment of the dynamics of nuclear spin systems is highly dependent on quantum mechanics. More precisely, Residual Dipolar Coupling (RDC) provides global orientation information of magnetic dipole-dipole interaction in a reference frame and distance-independent angular insights to local relaxation. RDC measurements necessitates the use of an anisotropic orientation medium for the partial alignment of the target molecule with respect to the magnetic field. Such media include liquid crystals or paramagnetic centers with a lanthanide ion. Anisotropic paramagnetic tags have been successful in biomolecular NMR applications of large proteins but their use in small organic molecules remains imperfect due to challenges in designing functional lanthanide-complexes with varying degrees of nondirectional bonding in the Ln(III) inner coordination sphere. In this study, we propose a strategy for the synthesis of a lanthanide tag and the measurement of RDCs in a target organic molecule using several paramagnetic lanthanide complexes.
Activation of Gαq sequesters specific transcripts into Ago2 particles
Authors: Jackson Lela , Poussaint Alison , Scarlata Suzanne
Published: October 2021

Hormones and neurotransmitters can activate the Gαq / phospholipase Cβ1 (PLCβ1) signaling system eliciting cellular calcium responses. PLCβ1 also prevents the aggregation of ribosomal and RNA proteins into stress granules, which are halted translation complexes that form in response to cellular stress. Activation of Gαq promotes PLCβ1association releasing bound proteins and promoting the formation of stress granules. However, the cellular impact of stress granules formed from routine Gαq protein signaling is unknown. Here, we have characterized Ago2 stress granules formed in response to Gαq activation in a neuronal-like cell line. We find these stress granule have a distinct protein composition, and unlike stress granules formed under heat stress, contain only two mRNA transcripts, chromogranin B, which is involved in secretory function, and ATP synthase 5f1b, which is required for ATP synthesis. Our studies show an unexpected pathway where Gαq/PLCβ regulates the translation of specific proteins.
Weight-Loss Behaviors of Avoiding Between Meal and Midnight Snack in Teenagers Associated with Gestational Diabetes: The Japan Environment and Children’s Study
Authors: Minami Marina , Watanabe Takafumi , Eitoku Masamitsu , Maeda Nagamasa , Fujieda Mikiya , Suganuma Narufumi
Published: October 2021

Background: Dietary habits and weight control before pregnancy are important in preventing gestational diabetes. This study aims to examine whether the weight-loss behavior of avoiding between meal and midnight snacks in teenagers is associated with subsequent gestational diabetes mellitus (GDM).Methods: A total of 89,227 (85.7% of the total) mother-infant pairs of live births were included in our study of the Japan Environment and Children's Study (JECS). In the second or third trimesters, participants were asked to report their weight-loss behaviors during their teenage years. Response items included avoidance of meals and midnight snacking. The main outcome of our study was the prevalence of GDM.Results: Overall, 2,066 (2.3%) participants had GDM. Relative to those without GDM, women with GDM were older, were smokers, had a higher prevalence of hypertension, previous cesarean delivery, mental illness, and higher body mass index (BMI). Weight-loss behavior in their teenage years was associated with a decreased risk of GDM (unadjusted crude odds ratio, 0.83; 95% confidence interval [CI]: 0.76–0.91), model 1 (adjusted odds ratio [aOR], 0.86; 95% CI: 0.79–0.94), and model 2 (aOR, 0.80; 95% CI: 0.73–0.88). Weight-loss behavior in teens was associated with a decreased risk of GDM in the normal weight [aOR, 0.79; 95% CI: 0.70–0.89) and overweight (aOR, 0.82; 95% CI: 0.69–0.98) groups.Conclusions: The results suggest that weight-loss behaviors of avoiding in-between meals and midnight snacking as teenagers are associated with a decreased risk of developing GDM.
DAXX-ATRX-H3.3 Regulation of p53 Chromatin Binding and DNA Damage Response
Authors: Gulve Nitish , Deng Zhong , Soldan Samantha , Vladimirova Olga , Wickramasinghe Jayamanna , Zheng Hongwu , Kossenkov Andrew , Lieberman Paul
Published: October 2021

DAXX and ATRX are tumor suppressor proteins that form a histone H3.3 chaperone complex and are frequently mutated in cancers with the alternative lengthening of telomeres (ALT), such as pediatric glioblastoma. Rapid loss of function of either DAXX or ATRX are not by themselves sufficient to induce the ALT phenotype. However, cells lacking DAXX or ATRX can be readily selected for ALT-like features. Here, we show that DAXX and ATRX null glioblastoma cells with ALT-like features have defects in p53 chromatin binding and DNA damage response regulation. RNA-seq analysis of DAXX or ATRX null U87 glioblastoma cells with ALT-like features revealed that p53 pathway is among perturbed. ALT-selected DAXX and ATRX-null cells had aberrant response to DNA damaging agent etoposide. Both DAXX and ATRX-null ALT cells showed a loss of p53 binding at a subset of response elements. Complementation of DAXX null cells with a wild-type DAXX transgene rescued p53 binding and transcription, while the tumor associated mutation L130R that disrupts ATRX binding was incapable of rescuing p53 chromatin binding. We show that histone H3.3 binding is reduced in DAXX-null cells especially at subtelomeric p53 binding sites and telomere repeats. These findings indicate that DAXX and ATRX function to enable p53 chromatin binding through modulation of histone H3.3 binding, especially at sub-telomeric sites.
A phylogenetically-restricted essential cell cycle progression factor in the human pathogen Candida albicans
Authors: Jaitly Priya , Legrand Melanie , Das Abhijit , Patel Tejas , Chauvel Murielle , d'Enfert Christophe , Sanyal Kaustuv
Published: October 2021

Chromosomal instability in fungal pathogens caused by cell division errors is associated with antifungal drug resistance. To identify mechanisms underlying such instability and to uncover new potential antifungal targets, we conducted an overexpression screen monitoring chromosomal stability in the human fungal pathogen Candida albicans. Analysis of ~1000 genes uncovered six chromosomal stability (CSA) genes, five of which are related to cell division genes in other organisms. The sixth gene, CSA6, is selectively present in the CUG-Ser clade species that includes C. albicans and other human fungal pathogens. The protein encoded by CSA6 localizes to the spindle pole bodies, is required for exit from mitosis, and induces a checkpoint-dependent metaphase arrest upon overexpression. Together, Csa6 defines an essential CUG-Ser fungal clade-specific cell cycle progression factor, highlighting the existence of phylogenetically-restricted cell division genes which may serve as potential unique therapeutic targets.
Protein Partitioning In A Droplet-Based Aqueous-Two Phase System Microfluidic Device
Authors: Cid David Hernández , Gallo-Villanueva Roberto Carlos , González-Valdez José , González Victor Hugo Pérez , Mata-Gómez Marco Arnulfo
Published: October 2021

Aqueous-Two Phase Systems (ATPS) is an important tool for the separation of biological entities as proteins, membranes, enzymes, among others. On the other hand, microfluidics is an emerging technology that studies and manipulates liquids either one single phase or dispersed fluids such as droplets at the micro or smaller scales. Applications of microfluidics in different areas such as molecular biology, biochemical analysis and bioprocess have increased in the last years. In this work, we proposed a droplet-based microfluidic approach to generate ATPS systems and to observe how two model proteins, native ribonuclease A (RNase A) and its PEGylated form (PEG-RNase A), behave and partition on these systems. Using polyethylenglycol (PEG) and potasium phosphate salts as the phase-forming chemicals, we were able to form ATPS systems inside the microfluidic device as commonly performed in conventional ATPS macrosystems. Even more, formation of ATPS systems in which one of the fluids was present as a droplet was also achieved. As expected, model proteins exhibited the same behavior as they do in a macrosystem, that is, they displaced to a particular phase according to their affinity for them. When native RNase A was placed in the salt-rich phase, it remained there, and migrated from the PEG-rich phase to the former. On its part, PEGylated RNase A remained in the PEGrich phase or migrated from salt-rich phase to the PEG-rich phase. These results open the possibility for a prospect of micro bioprocess to separate interest biomolecules.
The differential diagnosis of IgG4-related disease based on machine learning
Authors: Yamamoto Motohisa , Nojima Masanori , Kamekura Ryuta , Kuribara-Souta Akiko , Uehara Masaaki , Yamazaki Hiroki , Yoshikawa Noritada , Aochi Satsuki , Mizushima Ichiro , Watanabe Takayuki , Nishiwaki Aya , Komai Toshihiko , Shoda Hirofumi , Kitagori Koji , Yoshifuji Hajime , Hamano Hideaki , Kawano Mitsuhiro , Takano Ken-ichi , Fujio Keishi , Tanaka Hirotoshi
Published: October 2021

Introduction:
To eliminate the disparity and maldistribution of physicians and medical specialty services, the development of diagnostic support for rare diseases using artificial intelligence is being promoted. Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a rare disorder often requiring special knowledge and experience to diagnose. In this study, we investigated the possibility of differential diagnosis of IgG4-RD based on basic patient characteristics and blood test findings using machine learning.
Methods
Six-hundred and two patients with IgG4-RD and 212 patients with non-IgG4-RD that needed to be differentiated who visited the participating institutions were included in the study. Ten percent of the subjects were randomly excluded as a validation sample. Among the remaining cases, 80% were used as training samples, and the remaining 20% were used as test samples. Finally, validation was performed on the validation sample. The analysis was performed using a decision tree and a random forest model. Furthermore, a comparison was made between conditions with and without the serum IgG4 concentration. Accuracy was evaluated using the area under the receiver-operating characteristic (AUROC) curve.
Results
In diagnosing IgG4-RD, AUROC curve values of the decision tree and the random forest method were 0.905 and 0.970, respectively, when serum IgG4 levels were included in the analysis. Excluding serum IgG4 levels, the AUROC curve value of the analysis by the random forest method was 0.919.
Conclusion
Based on machine learning in a multicenter collaboration, with or without serum IgG4 data, basic patient characteristics and blood test findings alone were sufficient to differentiate IgG4-RD from non-IgG4-RD.
High-Performance BaTiO3 Film Based on Aqueous Tape Casting for Ultrathin MLCC Applications
Authors: Wang Pengfei , Zhang Lei , Yu Shuhui , Cao Xiuhua , Fu Zhenxiao , Sun Rong
Published: October 2021

The authors have requested that this preprint be removed from Research Square.
Clinical presentations and surgical outcomes of hemifacial spasm involving the vertebral artery
Authors: Li Jianguo , Lyu Liang , Chen Cheng , Yin Senlin , Jiang Shu , zhou peizhi
Published: October 2021

ObjectivesWe aimed to determine whether vertebral artery (VA) affects the success rate of microvascular decompression(MVD) in hemifacial spasm(HFS) patients. We compared the clinical presentations and surgical outcomes between VA-involved and non-VA HFS patients.MethodsThe study comprised 313 HFS patients who underwent MVD between January 2015 and December 2018. There were 59 patients in the VA-involved group and 254 patients in the non-VA group. The clinical results mainly included the rate of HFS remission and the complications. Postoperative neurosurgery-related problems and neurological issues were among the complications.ResultsAmong the 313 enrolled patients, 288 were spasem-free: 52 (88%) in VA-involved group and 236 (91.4%) in non-VA group. Delayed and partial remissions were frequent in VA-involved group. Furthermore, VA was significantly associated with partial remission (P=0.014). The total rate of complications was comparable between the two groups. However, motor or sensory impairments mainly occurred in the VA-involved group.ConclusionsThe rates of long-term remission and overall complication after MVD were not significantly different between the groups. VA-involved HFS may be at high risk for severe neurological complications and the partial spasem-free.
Unrelated Umbilical Cord Blood Transplantation For Children With Hereditary Leukodystrophy: Single Center Experience
Authors: Wang Ping , Du Xiaonan , Shen Quanli , Jiang Wenjin , Shen Chen , Wang Hongsheng , Zhou Shuizhen , Wang Yi , Qian Xiaowen , Zhai Xiaowen
Published: October 2021

Background

Hereditary leukodystrophies are diverse metabolic diseases caused by gene mutations that result in the abnormal development or degeneration of myelin. Transplantation of matched sibling donor umbilical cord blood (UCB) can slow progression and prolong survival in some cases. For patients without siblings, however, UCB transplantation from unrelated donors may be the only option.
Methods

This retrospective study assessed unrelated UCB transplantation (UCBT) efficacy following busulfan- and cyclophosphamide-based myeloablative chemotherapy.
Results

The study cohort included 12 pediatric patients (ten males), nine with adrenoleukodystrophy (ALD) and three with globoid cell leukodystrophy (GLD), treated between April 2015 and March 2020. All received HLA-matched or partially mismatched UCBT. Median age at UCBT was 7.2 years (range, [0.8–12.9 years]). There were no cases of graft rejection. Median neutrophil engraftment time was 20 days [12–33 days] and median platelet engraftment time was 29 days [14–65 days]. Median follow-up was 28 months [1–73 months], and overall survival rate was 83.3% (10/12). Seven patients had higher Loes scores post-transplantation, and two patients died of infection. Four patients with rapid neurological deterioration pre-UCBT exhibited worse neurological symptoms post-UCBT. In contrast, four patients with stable neurological symptoms pre-UCBT demonstrated symptom stability post-UCBT, and two with no neurological symptoms pre-UCBT were also symptom-free post-UCBT. Further, lipid profiles of surviving ALD patients were improved post-treatment.
Conclusions

Hereditary leukodystrophy patients with mild neurological symptoms can benefit from UCBT, while UCBT cannot reverse advanced disease.
Conditional Knockout of PDK1 in Osteoclasts Suppressed Osteoclastogenesis and Ameliorated Prostate Cancer-Induced Osteolysis
Authors: Zhang Yanan , Nong Haibin , Bai Yiguang , Zhou Quan , Zhang Qiong , Liu Mingfu , Liu Pan , Zeng Gaofeng , Zong Shaohui
Published: October 2021

Background: The development and maintenance of normal bone tissue is supported by balanced communication between osteoblasts and osteoclasts. The invasion of cancer cells disrupts this balance, leading to osteolysis. As the only bone resorption cells in vivo, osteoclasts play important roles in cancer-induced osteolysis. However, the function of 3-phosphoinositide–dependent protein kinase-1 (PDK1) in osteoclast resorption remains unclear. Methods: In our study, we used a receptor activator of nuclear factor-kappa B (RANK) promoter‐driven Cre‐LoxP system to conditionally delete the PDK1 gene in osteoclasts in mice. We investigated the impact of Osteoclast‐specific knockout of PDK1 on prostate cancer-induced osteolysis. Bone marrow-derived macrophage cells (BMMs) were extracted and induced to differentiate osteoclasts in vitro to examine the function of PDK1 in osteoclasts.Results: In this study, we found that PDK1 conditional knockout (cKO) mice exhibited smaller body sizes when contrasted with the wild-type (WT) mice. Moreover, deletion of PDK1 in osteoclasts ameliorated osteolysis and reduced bone resorption markers in the murine model of prostate cancer-stimulated osteolysis. In vivo, we discovered that osteoclast‐specific knockout of PDK1 suppressed RANKL-stimulated bone resorption function, osteoclastogenesis, and osteoclast-specific gene expression (Ctsk, TRAP, MMP-9, NFATc1). Western blot analyses of RANKL-induced signaling pathways showed that conditional knockout of PDK1 in osteoclasts inhibited the early nuclear factor κB (NF-κB) activation, which consequently suppressed the downstream induction of NFATc1. Conclusion: These findings demonstrated that PDK1 performs an instrumental function in osteoclastogenesis and prostate cancer-induced osteolysis by modulating the PDK1/AKT/NF-κB signaling pathway.
Redes Neurais Convolucionais para Classificação da COVID-19 em Imagens de Raio-x de Tórax
Authors: Farias Ricardo de Sousa , Oliveira Kaique Rijkaard de Sousa , Regis Carlos Danilo Miranda , Costa Cecília de Moura , Seixas José Manoel
Published: October 2021

A COVID-19 tem causado pânico e transtornos pelo mundo, principalmente pela sua forma de contágio e às altas taxas de internação em Unidades de Terapia Intensiva (UTI). Os infectados por COVID-19, geralmente apresentam sintomas que acometem o sistema respiratório. A análise de imagens de raio-x de tórax têm auxiliado o entendimento do quadro clínico dos pacientes com COVID-19, possibilitando uma melhor perspectiva dos impactos causados no pulmão. Este trabalho aborda a classificação de imagens de raio-x em três classes distintas: COVID-19, Normal e Pneumonia Viral, utilizando oito diferentes modelos convolucionais de aprendizado profundo, sendo eles a VGG16, VGG19, InceptionV3, ResNet50, InceptionResNetV2, Xception, DenseNet201 e NASNetLarge. Na classificação binária de COVID-19 e Normal, o modelo Xception se destacou na maioria da medidas de desempenho com valores em torno de 99\%. Na classificação binária entre COVID-19 e Pneumonia Viral, o modelo DenseNet201 alcançou os melhores resultados na maioria das medidas de desempenho em torno de 98%. Na classificação multiclasse a DenseNet201 alcançou os melhores resultados em quatro das seis medidas de desempenho com valores entre 94% e 96%.
Multi-station calibration strategy for evaluation and sensitivity analysis of the snowmelt runoff model using MODIS satellite images
Authors: Nourani Vahid , Afkhaminia Amin , Andaryani Soghra , Zhang Yongqiang
Published: October 2021

In this study, the snowmelt runoff model (SRM) was employed to estimate the effect of snow on the surface flow of Aji-Chay basin, northwest Iran. Two calibration techniques were adopted to enhance the calibration. The multi-station calibration (MSC) and single-station calibration (SSC) strategies applied to investigate their effects on the modeling accuracy. The runoff coefficients (cs and cr) were selected as calibration parameters because of their uncertainty in such an extended basin. To determine the most substantial input of the model which is the snow-covered area (SCA) from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor imagery, MOD10A2 images were collected with spatial and temporal resolutions of 500 meters and 8 days, respectively. The results show an average of 15% improvement in the model performance in the MSC strategy from the data period of 2008–2012. Also, an appropriate agreement with physical characteristics of the study area could be seen for the calibration parameters. The contribution of snowmelt in the river flow reaches its peak in April and May, then with increasing temperature, the contribution decreased gradually. Furthermore, analysis of parameters indicates that the SRM is sensitive to recession coefficient and runoff coefficients.
LAGOM IN THE SWEDISH CULTURE (ON THE EXAMPLE OF THE GASTRONOMIC DISCOURSE)
Authors:   Private educational institution of additional education for the study of foreign languages “Nordic School”, ULYANA P. PRIRODINA
Published: October 2021

This article is devoted to the question of the word lagom in the Swedish language and the culture of the ethnic group. The analysis revealed the etymology of the word lagom and described its role in the Swedish society, as well as presented the semantics of the word lagom with the support of its functioning at the level of the gastronomic discourse. The following research methods were used in the work: observation method, descriptive method and method of etymological analysis. The analysis of the material made it possible to conclude that the word lagom reflects the value attitudes developed by the historically developing social consciousness, the way of ethnic life, and the worldview. The word lagom , denoting the ideal amount, with the help of which the search for moderation in everything and balance in all spheres of life is carried out, has a direct bearing on gastronomy. The semantic structure of the word lagom in the Swedish gastronomic discourse is characterized by inconsistency.
SOMATIC CODE OF THE CULTURE IN INGUSH PROVERBS AND SAYINGS
Authors:   Ingush State University, MILANA T. KHAMKHOEVA
Published: October 2021

In the Ingush proverbs and sayings somatic words are one of ways to form value of concepts of the internal and external world of the person. Various representations about body parts have laid down in a basis of semantics of various figurative means which have served for the characteristic of spiritually-moral, intellectual, emotionally-mental, physical, social qualities of the person.
RHETORICAL CULTURE OF THE MODERN INFORMATION SOCIETY IN THE ASPECT OF SPEECH EFFICIENCY
Authors:   Astrakhan State University, IRINA Y. CHISTYAKOVA
Published: October 2021

The article is devoted to the research of public speaking of the modern information society in the aspect of speech efficiency. The main focus is on political, educational and cultural discourses, polemical television genres.
TERMINOLOGICAL ACTUALIZATION OF MODERN TECHNICAL KNOWLEDGE: COGNITIVE-DERIVATION ASPECT
Authors:   Kuban State University, LUDMILA YU. BUYANOVA , DARIA I. NOVOSELETSKAYA ,   Krasnodar Higher Military School named after General of the Army S.M. Shtemenko
Published: October 2021

Theoretical issues of terminological actualization of technical knowledge, status and functional amplitude of technical terms are investigated. The evolutionary significance of technical terminological semiosis is noted: the emergence of more and more classes of technical terms contributes to the replenishment of the terminology fund of the national language and the language of science as a whole. The process of terminological actualization is determined, which is a cognitive-derivational activity to create a term; the plurality of interpretation of the concept "term" as a means of verbalizing technical knowledge is considered. The term "cluster" is introduced and substantiated as the nomination of the mega-complex of modern technical sciences; shows its substantive efficiency in comparison with the term "subject area".
MODELING FEATURES IN DECISION-MAKING IN THE FIELD OF PROFESSIONAL MEDICAL EDUCATION
Authors:   Novokuznetsk State Institute of Improvement of Doctors, ANDREI A. KOZHEVNIKOV
Published: October 2021

The article presents an approach to modeling decision-making in the process of professional medical education, taking into account the theory of management. Possibilities of application of the method developed by the author on analysis of parameters of "problem field" and minimization of factors of "uncertainty" in selection of themes and educational material based on application of indices of presence of problems are considered. The purpose of the study was to consider decision-making issues in the field of professional medical education based on management theory in order to increase the competence of teachers and students, as well as to form educational programs and educational projects taking into account industry specifics and existing restrictions. As a method of research, modeling was used, including sign modeling, including using mathematical methods and ratios; system analysis; and methods of situational and logical analysis of management problems for setting and selecting alternatives to solve research problems. In addition, strategic reflection was assessed against the background of industry specifics and existing restrictions in the training of specialists in the field of health care, as well as the likelihood of ensuring a Nash-equilibrium vector of actions corresponding to the topic under consideration. The conclusions contain proposals for the introduction of this approach in the formation of educational services in order to increase their manageability and achieve their goals.
3D VISION SYSTEM FOR UNDERWATER ROBOT
Authors:   Sevastopol State University, ALEKSEY A. KABANOV , VADIM A. KRAMAR ,   Sevastopol State University, OLEG A. KRAMAR ,   Sevastopol State University
Published: October 2021

The article deals with the development of an integrated high-resolution 3D vision system for remotely controlled and autonomous underwater robotic systems. The problem of developing a 3D vision system as a sensor subsystem of an underwater robot is presented. Typical examples of tasks solved with the help of such robotic systems are environmental monitoring; detection of objects and obstacles, their localization; convergence of the CRS with the object; performing operations with objects. The structure of a complex 3D vision system is presented. The description of the design of the main structural elements of the system is given, the main functionality of the developed test software is described. The technical characteristics of the subsystems are given, such as the module for the near-vision of the 3D vision system, the module for additional lighting, and the module for far vision. The description of the developed software for processing video data of a stereo camera (stereo module) in real-time is given. The paper presents the results of the test approbation of software that implements many algorithms for 3D reconstruction of the working space of an underwater robot based on information received from the stereo vision module. The approbation was carried out on the operating model of the underwater stereo vision module connected to the developed underwater robot. The study of the characteristics of a complex 3D vision system was carried out in an aquarium. The effectiveness of the developed system was shown by the experiments with the underwater robot.