bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Effectiveness of Omnitrope® (Somatropin) in PATRO Children: A Multi-Center, Post-Marketing Surveillance Study Comparison of United States and Rest of World Data
Authors: Backeljauw Philippe , Kanumakala Shankar , Loche Sandro , Schwab Karl Otfried , Miller Bradley S , Levy Richard , McCormick Kenneth , Zouater Hichem , Zabransky Markus , Campbell Kim
Published: September 2021

PAtients TReated with Omnitrope® (PATRO) Children is an international, non-interventional study with Omnitrope® (somatropin, Sandoz Inc.), conducted across 14 different countries. Here we present a comparison of safety and effectiveness data from patients in the United States (US) and in other countries. All visits and assessments are carried out according to routine clinical practice, and doses of Omnitrope® are given according to country-specific prescribing information. By September 2018, 294 patients had been enrolled in the US (53.1% recombinant human growth hormone [rhGH]-naïve) and 6206 patients had been enrolled across 13 other countries (international group; 86.2% rhGH-naïve). The most common indication in both groups was growth hormone deficiency (GHD). Overall, 194 US patients (66.0%) and 2977 international patients (48.0%) experienced adverse events (AEs; 886 and 11,716 events, respectively), most of which were of mild or moderate intensity. The AEs were suspected to be treatment-related in five US patients (1.7%) and 452 international patients (7.3%). All reported neoplasms were benign, non-serious, and considered unrelated to rhGH therapy. No cases of diabetes mellitus or hyperglycemia were reported. In rhGH-naïve GHD patients, after 3 years of rhGH therapy, the improvement in mean height SD score from baseline was +1.25 and +1.35 in US and international patients, respectively. Conclusion Omnitrope® treatment appears to be well tolerated and effective in US patients and those from other countries. Across the pediatric indications included, there was no evidence of an increased risk of developing uncommon or unexpected AEs with rhGH.Trial registration: NA
A Novel Optimized Finite Element Model of Lenke 1 Adolescent Idiopathic Scoliosis Based on Dynamic Flexibility in Vivo
Authors: Niu Shengbo , Bai Jinyi , Yang Huan , Zhang Dongsheng , Wu Jianghong , Liu Siyong , Yang Changwei , Li Ming
Published: September 2021

Bacground: It is of great significance to optimize the finite element model by spinal flexibility of adolescent idiopathic scoliosis (AIS) patients. The elastic modulus of the intervertebral disc is of critical importance in determining the overall flexibility of the spine. The aim of the present study was to optimize the finite element model of Lenke 1 AIS based on the dynamic flexibility in vivo by matching the optimal elastic modulus of the intervertebral disc.Methods: The Cobb angles under different longitudinal traction loads of one patient with Lenke 1 AIS were dynamically measured by using a spine morphometer with a posture sensor to plot the Cobb angle-longitudinal traction load characteristic curve. A 3D finite element model of the patient was established. The patient’s Cobb angle-longitudinal traction load characteristic curve was used as the dynamic flexibility in vivo to determine the optimal intervertebral disc elastic modulus of the model. Results: The dynamic flexibility curve in vivo of one Lenke 1 AIS patient was successfully obtained, and the patient’s optimal elastic modulus of the intervertebral disc for the finite element model was 5 MPa according to the dynamic flexibility curve in vivo.Conclusions: The use of dynamic flexibility in vivo to optimize the finite element model can provide a new perspective and approach for model optimization, which can reproduce the biomechanical characteristics in vivo of AIS patients.
Association between health literacy and risk of depressive symptoms among Chinese college students
Authors: Ren Zhongyu , Cao Jianhua , Cao Bing , E Shuang , Kuang Jujiao
Published: September 2021

Background

The association between health literacy and depressive symptoms has been examined among Chinese middle school students, however there is no evidence are available from college students.
Aims

This study aimed to examined the association between health literacy and depressive symptoms among Chinese college students.
Methods

This cross-sectional study recruited 2771 college students in Southwest University. Depressive symptoms was assessed using Zung self-rating depression scale and a score of ≥ 50 represented having depressive symptoms. We used Chinese adolescent interactive health literacy questionnaire to assess health literacy. Multivariate logistic regressions analysis was applied to assess the association between health literacy and depressive symptoms.
Results

The prevalence of depressive symptoms was 34.9% (967/2771). Multivariate logistic regressions analysis showed an inverse association between health literacy and depressive symptoms after adjusting for potential confounders. The multivariate adjusted ORs (95%CIs) for depressive symptoms across quartiles of health literacy level were 1.000 (reference), 0.48 (0.39, 0.60), 0.25 (0.19, 0.32), and 0.16 (0.12, 0.21) (P for trend: <0.001). Similar associations were also found when all 6 health literacy dimensions were analyzed separately.
Conclusion

The results of this cross-sectional study indicated that higher health literacy level was associated with lower risks of depressive symptoms. Further prospective studies or randomized controlled trials should be conducted to prove the causal association between health literacy and risk of depressive symptoms.
XJP Inhibits Apoptosis, Invasion, EMT, and Wnt/Β-Catenin Pathway in Triple-Negative Breast Cancer
Authors: Feng Dandan , Chen Hongzhi , Shi Guangxi , Zhang Mengdi , Liang Hongyi , Liu Zhiyong , Li Jingwei
Published: September 2021

Background: Triple-negative breast cancer (TNBC) progresses at a rapid pace. Chemotherapy is a major clinical application. However, resistance and metastases are key barriers to chemotherapy. Xiaojin pills (XJP) have been used clinically for treating TNBC for decades. However, the potential molecular mechanisms of the effect of XJP on breast cancer is still not understood.Methods: The cell viability was analyzed using Cell Counting Kit-8 (CCK-8). Flow cytometry was used to detect apoptosis, and the migration and invasion abilities of TNBC were assessed using Transwell assay. For molecular mechanisms, the protein expression levels were determined by Western blot analysis. The expression of β-catenin in the Wnt/β-serial protein (β-catenin) pathway was detected with immunofluorescence (IF).Results: XJP inhibited the viability and proliferation of the TNBC cell line in vitro. Flow cytometry analysis showed that apoptosis increased in both MDA-MB-231 and MDA-MB-468 cells induced by XJP. The expression of the proteins associated with invasion, for example, matrix metalloproteinase (MMP) and MMP9, was reduced. Among epithelial–mesenchymal transition markers, E-cadherin was upregulated and N-cadherin was downregulated. The apoptosis-related proteins caspase-8, caspase-3, caspase-9, and Parp were all upregulated. Additionally, XJP effectively suppressed the expression of β-catenin, which belonged to the Wnt/β-catenin pathway.Conclusions: These results suggested that XJP suppressed the progression of TNBC cells by suppressing apoptosis, invasion, EMT, and Wnt/β-catenin pathway.
A Novel Push-pull Central-lever Mechanism Reduces Peak Forces and Energy-cost Compared to Hand-rim Wheelchair Propulsion During a Controlled Lab-based Experiment
Authors: Rütte Thomas A le , Trigo Fransisca , Bessems Luca , Woude Lucas HV van der , Vegter Riemer JK
Published: September 2021

Background: Hand-rim wheelchair propulsion is straining and mechanically inefficient, often leading to upper limb complaints. Previous push-pull lever propulsion mechanisms have shown to perform better or equal in efficiency and physiological strain. Propulsion biomechanics have not been evaluated thus far. A novel push-pull central-lever propulsion mechanism is compared to conventional hand-rim wheelchair propulsion, using both physiological and biomechanical outcomes under low-intensity steady-state conditions on a motor driven treadmill. Methods: In this 5-day (distributed over a maximum of 21 days) between-group experiment, 30 able-bodied novices performed 60 minutes (5x3x4 min) of practice in either the push-pull central lever wheelchair (n=15) or the hand-rim wheelchair (n=15). At the first and final sessions cardiopulmonary strain, propulsion kinematics and force production were determined in both instrumented propulsion mechanisms. Repeated measures ANOVA evaluated between (propulsion mechanism type), within (over practice) and interaction effects. Results: Over practice, both groups significantly improved on all outcome measures. After practice the peak forces during the push and pull phase of lever propulsion were considerably lower compared to those in the handrim push phase (42±10 & 46±10 vs 63±21 N). Concomitantly, energy expenditure was found to be lower as well (263±45 vs 298±59 W), on the other hand gross mechanical efficiency (6.4±1.5 vs 5.9±1.3 %), heart-rate (97±10 vs 98±10 bpm) and perceived exertion (9±2 vs 10±1) were not significantly different between modes.Conclusion: The current study shows the potential benefits of the newly designed push-pull central-lever propulsion mechanism over regular hand rim wheelchair propulsion. The much lower forces and energy expenditure might help to reduce the strain on the upper extremities and thus prevent the development of overuse injury. This proof of concept in a controlled laboratory experiment warrants continued experimental research in wheelchair-users during daily life.
3-HAA Metabolic Pathway Regulates HCC Growth
Authors: Shi Zhaopeng , Gan Guifang , Gao Xianfu , Chen Fuxiang , Mi Jun
Published: September 2021

Background

Kynurenine, a metabolite of tryptophan, promotes immune tolerance in development and tumor evasion by binding to the aryl hydrocarbon receptor (AHR). However, the kynurenine catabolic enzyme IDO1 inhibitors fail in clinical trials.
Methods

The LC-MS/MS and GC-MS/MS were performed to measure the concentration of tryptophan metabolites. The PCX model, PDX model, and transposon liver cancer models were used to evaluate the effects of 3-HAA, DUSP6, and YY1 on HCC tumor formation and/or tumor growth.
Results

3-hydroxyanthranilic acid (3-HAA) induced HCC apoptosis and reduced xenografted tumor growth, the survival of the transposon HCC mice, and synergized with IDO1 inhibitor on HCC growth in vivo. Overexpression of 3-HAA synthesis enzyme KMO suppressed tumor formation and tumor growth by increasing endogenous 3-HAA while adding exogenous 3-HAA also inhibited tumor growth. Notably, 3-HAA was lower in tumor cells due to the downregulation of its synthetic enzyme KMO/KYNU and/or upregulation of its catalytic enzyme HAAO. The mechanistic investigation demonstrated that 3-HAA induced dual-specificity phosphatase 6 (DUSP6) transcription. DUSP6 overexpression induced apoptosis of hepatocellular carcinoma (HCC) cells and suppressed the HCC growth in vitro and in vivo. DUSP6 knockdown abolished 3-HAA-induced apoptosis and restores tumor growth.
Conclusions

These findings demonstrate that 3-HAA metabolic pathway regulates HCC cell growth, suggesting it is a promising therapeutic candidate for HCC.
Evaluation of Cardiac Functions By Speckle Tracking Echocardiography in Type 2 Diabetes Mellitus With Hyperlipidemia
Authors: Dong Zhizhi , Zhou Jun , Chen Yue , Liu Zulin , Shi Douzi , Zhou Chang , Liu Rong
Published: September 2021

Background

To investigate the value of two-dimensional speckle tracking echocardiography (2D-STE) in evaluating cardiac functions in type 2 diabetes mellitus (T2DM) with hyperlipidemia.
Methods

Sixty T2DM patients with normal left ventricular ejection fraction (LVEF) and poorly-controlled blood glucose were selected. Among these, thirty had hyperlipidemia. Thirty age- and gender-matched healthy individuals were recruited as the normal control group. Longitudinal strain of left ventricular segments, left ventricular global longitudinal strain (LV GLS), left atrial global longitudinal strain (LA GLS), right ventricular global longitudinal strain (RV GLS) and right atrial global longitudinal strain (RA GLS) were measured by 2D-STE.
Results

(1) Compared with the normal control group, LV GLS in T2DM group and T2DM with hyperlipidemia group decreased (P < 0.05), but there was no significant difference of LV GLS between T2DM group and T2DM with hyperlipidemia group (P > 0.05). Compared with the normal control group and T2DM group, longitudinal strain of middle segment of LV in T2DM with hyperlipidemia group decreased (P < 0.05). (2) There was a significant difference in LA GLS among the three groups. LA GLS of T2DM with hyperlipidemia group was lower compared with the normal control and T2DM group (P < 0.05). (3) Compared with the normal control group, RV GLS in T2DM group and T2DM with hyperlipidemia group was lower (P < 0.05), but there was no significant difference of RV GLS between T2DM group and T2DM with hyperlipidemia group (P > 0.05). RA GLS in T2DM with hyperlipidemia group decreased (P < 0.05) compared to the normal control group and T2DM group.
Conclusion

Speckle tracking echocardiography can effectively evaluate cardiac dysfunction in patients with T2DM. LA GLS and RA GLS can be used as potential markers of cardiac dysfunction in T2DM with hyperlipidemia, and provide the basis for early clinical diagnosis and treatment.
Sarcopenia Increases the Risk of Major Organ Invasion in Patients with Papillary Thyroid Cancer
Authors: Yoon Ja Kyung , Yoon Jung Hyun , Park Vivian Youngjean , Lee Minah , Kwak Jin Young
Published: September 2021

While sarcopenia is associated with poor overall survival and cancer-specific survival in solid cancer patients, the impact of sarcopenia on clinicopathologic features that can influence conventional papillary thyroid cancer (PTC) prognosis remains unclear. To investigate the impact of sarcopenia on aggressive clinicopathologic features in PTC patients, prospectively collected data on 305 patients who underwent surgery for PTC with preoperative staging ultrasonography and bioelectrical impedance analysis were retrospectively analyzed. Nine sarcopenia patients showed more patients aged 55 or older (p = 0.022), higher male proportion (p < 0.001), lower body-mass index (p = 0.015), higher incidence of major organ invasion (p = 0.001), higher T (p = 0.002) stage, higher TNM (p = 0.007) stage, and more tumor recurrence (p = 0.023) compared to the non-sarcopenia patients. Unadjusted and adjusted logistic regression analyses showed that sarcopenia (odds ratio (OR) 9.936, 95% confidence interval (CI) 2.052–48.111, p = 0.004), tumor size (OR 1.048, 95% CI 1.005–1.093, p = 0.027), and tumor multiplicity (OR 3.323, 95% CI 1.048–10.534, p = 0.041) significantly increased the risk of major organ invasion. Therefore, sarcopenia in PTC patients should raise suspicion for a more locally advanced disease and direct appropriate management.
D-Dimer is a Predictive Factor of Cancer Therapeutics-Related Cardiac Dysfunction in Patients Treated With Cardiotoxic Chemotherapy
Authors: Oikawa Masayoshi , Yaegashi Daiki , Yokokawa Tetsuro , Misaka Tomofumi , Sato Takamasa , Kaneshiro Takashi , Kobayashi Atsushi , Yoshihisa Akiomi , Nakazato Kazuhiko , Ishida Takafumi , Takeishi Yasuchika
Published: September 2021

Background: D-dimer is a sensitive biomarker for cancer-associated thrombosis, but little is known about its significance on cancer therapeutics-related cardiac dysfunction (CTRCD). Methods: Consecutive 169 patients planned for cardiotoxic chemotherapy were enrolled and followed up for 12 months. All patients underwent echocardiography and blood test at baseline, as well as at 3-month, 6-month, and 12-month. Results: The patients were divided into 2 groups based on the level of D-dimer (> 1.65 µg/ml or ≦ 1.65 µg/ml) at baseline before chemotherapy: High D-dimer group (n = 37) and low D-dimer group (n = 132). Left ventricular ejection fraction (EF) decreased at 3-month and 6-month after chemotherapy in high D-dimer group (baseline, 65.2% [62.8%-71.4%]; 3-month, 62.9% [59.0%-67.7%]; 6-month, 63.1% [60.0%-67.1%]; 12-month, 63.3% [58.8%-66.0%], P = 0.03), but no change was observed in low D-dimer group. The occurrence of CTRCD within the 12-month follow-up period was higher in high D-dimer group than in low D-dimer group (16.2% vs. 4.5%, P = 0.0146). Multivariable logistic regression analysis revealed that high D-dimer level at baseline was an independent predictor of the development of CTRCD (odds ratio 3.93, 95% CI [1.00-15.82], P = 0.047). Conclusion: Elevated D-dimer is a pivotal biomarker to predict CTRCD.
Identification of IGF2BP2 as a Prognostic Biomarker and Immunotherapeutic Target Based on Alternative Splicing Events in Glioblastoma
Authors: Li Xin-Yu , Hou Lei , Zhang Lu-yu , Li Xue-yuan , Yang xi-tao
Published: September 2021

Aim: A glioblastoma (GBM) prognostic model was developed with GBM -related alternative splicing (AS) data and prognostic markers were identified. Methods: AS data and clinical data of GBM patients were retrieved from The Cancer Genome Atlas (TCGA) SpliceSeq database and TCGA database, respectively. The data from these two databases were intersected to screen the prognosis-associated AS events, which was subsequently examined in Univariate Cox regression models. To avoid model overfitting, LASSO regression analysis was conducted. On the basis of these AS events, we established a prognostic model of GBM with the use of multivariate Cox regression analysis. On the strength of this model, the patients were assigned into high-risk and low-risk groups with a median risk score as the threshold. Kaplan-Meier survival, receiver operating characteristic (ROC), and calibration curves were applied to evaluate the performance of this model. Finally, combined with the risk model and clinicopathological characteristics, Cox regression analysis was utilized to identify the independent prognostic markers of GBM, and a nomogram was constructed. Results: The AS and clinical data of 169 GBM patients from the TCGA SpliceSeq and TCGA databases were collected. Univariate Cox regression analysis identified 1000 prognosis-related AS events in GBM, and then Lasso regression analysis identified 16 AS events. A GBM prognostic risk model was constructed based on AS events of 7 genes (FAM86B1, ZNF302, C19orf57, RPL39L, CBLL1, RWDD1, IGF2BP2). Through this model, we found lower overall survival (OS) rates of the high-risk population versus the low-risk population (p < 0.05). ROC and calibration curve analyses demonstrated the good ability of this model to predict the OS of GBM patients. Cox regression analysis suggested risk score as an independent prognostic factor for GBM. We also found that IGF2BP2 is associated with patient prognosis and have a strong relationship with immunotherapy response. Conclusion: The prognostic model based on AS events can significantly distinguish the survival rate of high-risk and low-risk GBM patients and IGF2BP2 were identified as a novel prognostic biomarker and immunotherapeutic target.
Correlation Between Immune-related Adverse Events and Therapeutic Effects of Nivolumab in Patients With Malignant Pleural Mesothelioma
Authors: Yoneda Hiroto , Nokihara Hiroshi , Mitsuhashi Atsushi , Ozaki Ryohiko , Yabuki Yohei , Ogino Hirokazu , Otsuka Kenji , Nishioka Yasuhiko
Published: September 2021

Background: Nivolumab is used for the treatment of malignant pleural mesothelioma (MPM). However, immune-related adverse events (irAEs) occur in patients treated with nivolumab. Several studies have reported the correlation between irAEs and therapeutic effects of immune checkpoint inhibitor, but none have reported the correlation in MPM. Here we report a retrospective study which shows the correlation between irAEs and therapeutic effects of nivolumab in patients with MPM. Methods: This study included patients treated with nivolumab at Tokushima University Hospital from February 2009 to December 2019. We retrospectively reviewed the medical records to evaluate the several clinical factors, such as the presence or absence of irAEs, their severities, progression-free survival (PFS), overall survival (OS) or objective response to the treatment.Results: Eight patients received treatment with nivolumab. Overall response rate was 14.3% and the disease control rate was 87.5%. Median PFS was 6.6 months (95% confidence interval, 2.4 to 10.8 months) and median OS was 15.2 months (95% confidence interval, 11.1 to 19.4 months). IrAEs occurred in six patients (85.7%), and grade 2 ≤ irAEs occurred in four patients (50.0%). Median PFS was significantly longer in the grade 2 ≤ irAEs group (16.3 months) than in their counterpart (3.8 months; p = 0.0266).Conclusions: This is the first study to report the correlation between irAEs and therapeutic effects in patients with MPM. Because the presence of irAEs may be associated with a favorable clinical outcome, early detection and appropriate management of irAEs will increase the therapeutic benefits to patients.
Lipid Risk Factors of Coronary Heart Disease in Postmenopausal Women with Statins based on NMR Metabolomics
Authors: Li Chuang , CHEN Jingxun , Wei Siyue , Zhang Mei , Chu Yushun , Meng Fanpeng , Wang Jianyu , Tang Jie , Luo Jian , Yang Yu , Niu Xiulong , Cai Wei
Published: September 2021

Background The role of nuclear magnetic resonance (NMR) metabolomics in the prevention of coronary heart disease (CHD) in postmenopausal women is unclear.Objective To explore the NMR measured risk factors of CHD and the correlation among Gensini score, proprotein convertase subtilisin/kexin type-9 (PCSK9) and NMR metabolomics.Method 300 postmenopausal women who were under moderate intensity statins were enrolled and assigned into CHD Group (242) and non-CAHD Group (58). Multivariate Logistic regression and Spearman correlation analysis were conducted for the risk factors of CHD and the relationship among Gensini score, PCSK9 and NMR results in all patients as well as the patients with CHD, diabetes mellitus (DM) and metabolic syndrome (MS). ResultsAge, the particle of LDL-6, LDL-6- triglyceride (TG) and LDL-6-free cholesterol (FC) were risk factors of CHD, while, glycerol were the protective factors of CHD. Lipoprotein contents of very-low-density lipoprotein (VLDL)-2 ~ VLDL-5, intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL)-1 and LDL-2 were positively related to Gensini score, while the lipoprotein contents, apolipoprotein A1 (ApoA1) and ApoA2 of high-density lipoprotein (HDL)-1 ~ HDL-4 showed negative correlations with Gensini score. PCSK9 was negatively correlated to the particles of VLDL, IDL and LDL, total cholesterol (TC), ApoB/A1, and nearly all the lipid contents in VLDL-3 ~ VLDL-5, IDL and LDL-1.ConclusionIn postmenopausal women, under moderate intensity statins, age, and the NMR measured particle of LDL-6, LDL-6-TG and LDL-6-FC were risk factors of CHD, while glycerol were the protective factors of CHD. Lipoprotein contents of VLDL-2 ~ VLDL-5, IDL, LDL-1 and LDL-2 maybe the residual risk factors of CHD in postmenopausal women, who is under moderate intensive statin.
Impact of Electromagnetic Stirring on the Gas Metal Arc Welding of an MAR-M247 Superalloy
Authors: Tzeng Yu-Chih , Lu Cheng-Yu , Chen RenYu
Published: September 2021

In this paper, the impact of electromagnetic stirring (EMS) on the gas metal arc welding (GATW) of an MAR-M247 superalloy was investigated. Results revealed that, without electromagnetic stirring, it was easy for carbides in the heat-affected zone (HAZ) of the weld bead to liquefy during welding, leading to weld bead cracks. Electromagnetic stirring refined the grains in the HAZ and the weld bead, leading to grain strengthening and subsequently resulting in the effective improvement in the hardness of the weld bead. In addition, electromagnetic stirring significantly facilitated the formation of the weld bead by the removal of large inclusions which in turn effectively improved crack resistance at the joint. It also accelerated the floating up of gas holes thereby reducing the generation of gas hole defects.
Bipolar Plasma Kinetic Vaporization Resection in the Management of Benign Anastomotic Stricture after Rectal Cancer Surgery: A Report of 12 Cases
Authors: Zhang Shaopeng , Xiao Mingming , Wu Song , pan guoqiang , kong yuan , li wei
Published: September 2021

Background: Postoperative anastomotic stricture is a common complication after kinds of rectal cancer surgery, especially in low anterior resection and anal retention patients. Currently, various of treatments including anal expansion, endoscopic dilation and also surgery are applied with different efficacy and safety. Besides, bipolar plasma kinetic vaporization resection is a technique used to be applied for benign prostatic hyperplasia with minimally invasion and high safety. To the best of my knowledge, it had not been reported to be applied for narrow scars after rectal surgery.Methods: To analysis retrospectively the clinical data of 12 patients who suffered anastomotic strictures after rectal cancer surgery in the First Hospital of Jilin University from Feb 2015 to December 2017. Result：All of them were successfully treated by the technique of once bipolar plasma kinetic vaporization resection in 8 cases, twice in 3 cases, and more times in 1 cases without occurrence of additional complications. Conclusions: Demonstrated by these limited cases, bipolar plasma kinetic vaporization resection would be applied as an alternative method in the treatment of postoperative anastomotic strictures due to its advantages as well as its effectiveness and safety.
Synthesis and Macrocyclization-Induced Emission Enhancement of Benzothiadiazole-based Macrocycle
Authors: Li Chunju , Bai Yue-Ling , Cui Lei , Li Shuo
Published: September 2021

We presented a novel strategy for the improvement of luminophore’s solid-state emission, i.e., macrocyclization-induced emission enhancement (MIEE), by linking luminophores through C(sp3) bridges to give a macrocycle. Benzothiadiazole-based macrocycle (BT-LC) has been synthesized by a one-step condensation of the monomer 4,7-bis(2,4-dimethoxyphenyl)-2,1,3-benzothiadiazole (BT-M) with paraformaldehyde, catalyzed by Lewis acid. BT-LC shows strong emission in both dilute solution and aggregated state. Moreover, in comparison with the monomer, macrocycle BT-LC produces much more intense fluorescence in the solid state (ΦPL=99%) and exhibits better device performance in the application of OLEDs. The MIEE can be ascribed to the restriction of intramolecular motion and the alleviation of the concentration quenching by the macrocyclic topological structure.
Polymeric Photonic Quasicrystal: Octonacci Sequence and Elasto-optic Effect
Authors: NAYAK Chittarajan , Jena Shuvendu , Rout Satyam , Suthar Bhuvneshwer , Udupa Dinesh V.
Published: September 2021

Here we would like to discuss the light transmission modulation by the one-dimensional polymeric quasi-multilayer which is formed according to substitutional generalized Octonacci with PMMA and PS as the constituent materials. In particular, we will present some theoretical findings using the well-known transfer matrix method. PBG inter-band spacing and depth can be managed by choosing the appropriate generation number. The number of PBGs is the same while increasing in the generation number and are shifted symmetrically towards the designed frequency. It also reveals the aroused forbidden frequency band can be manipulated by changing the applied hydrostatic pressure and the thickness of the constituent polymeric materials. The increase in pressure shows a blue shift in the PBGs while the increase in thickness of the polymeric material provides a redshift to PBGs. The proposed structure could be another possible system for optical device design specially multi-band tunable optical reflectors.
regCOVID: Tracking publications of registered COVID-19 studies
Authors: Mayer Craig , Huser Vojtech
Published: September 2021

In response to the COVID-19 pandemic many clinical studies have been initiated leading to the need for efficient ways to track and analyze study results. We expanded our previous project that tracked registered COVID-19 clinical studies to also track result articles generated from these studies. We conducted searches of ClinicalTrials.gov and PubMed to identify articles linked to COVID-19 studies, and developed criteria based on the trial phase, intervention, location, and record recency to develop a prioritized list of result publications. We found 760 articles linked to 419 interventional trials (15.7% of all 2 669 COVID-19 interventional trials as of 15 August 2021), with 418 identified via abstract-link in PubMed and 342 via registry-link in ClinicalTrials.gov. Of the 419 trials publishing at least one article, 123 (29.4%) have multiple linked publications. We used an attention score to develop a prioritized list of all publications linked to COVID-19 trials and identified 58 publications that are result articles from late phase (Phase 3) trials with at least one US site and multiple study record updates. For COVID-19 vaccine trials, we found 69 linked result articles for 40 trials (13.9% of 290 total COVID-19 vaccine trials). Our method allows for the efficient identification of important COVID-19 articles that report results of registered clinical trials and are connected via a structured article-trial link.
Future temperature and salinity in Puget Sound, Washington State, under CMIP6 climate change scenarios
Authors: Walker Stevie , Morzaria-Luna Hem Nalini , Kaplan Isaac , Petatán-Ramírez David
Published: September 2021

In Washington State, climate change will reshape the Puget Sound marine ecosystem through bottom-up and top-down processes, directly affecting species at all trophic levels. To better understand future climate change effects on sea surface temperature and salinity in Puget Sound, we used empirical downscaling to derive high-resolution time series of future sea surface temperature and salinity. Downscaling was based on scenario outputs of two coarse-resolution General Circulation Models, GFDL-CM4 and CNRM-CM6-1-HR, developed as part of the Coupled Model Intercomparison Project Phase 6 (CMIP6). We calculated 30-year climatologies for historical and future simulations, calculated the anomalies between historical and future projections, interpolated to a high resolution, and applied the resulting downscaled anomalies to a Regional Ocean Modeling System (ROMS) time series, yielding short-term (2020–2050) and long-term (2070–2100) delta-downscaled forecasts. Downscaled output for Puget Sound showed temperature and salinity variability between scenarios and models, but overall, there was strong model agreement. Model variability and uncertainty was higher for long-term projections. Spatially, we found regional differences for both temperature and salinity, including higher temperatures in the South Basin of Puget Sound and higher salinity in the North Basin. This study is a first step to translating CMIP6 outputs to higher resolution predictions of future conditions in Puget Sound. Interpreting downscaled projections of temperature and salinity in Puget Sound will help inform future ecosystem-based management decisions, such as supporting end-to-end ecosystem modeling simulations and assessing local-scale exposure risk to climate change.
Research on A Novel MPP Tracking Strategy Reaction to Rapid Change of Light Intensity
Authors: Sun Chunhu , Ling Jing , Liu Tingting
Published: September 2021

For the misjudgment and oscillation in the traditional MPP tracking process when the light intensity changes rapidly, a novel improved optimal gradient method for power prediction is proposed, based on the research of the traditional power prediction method and the optimal gradient method.In this article, the working principle, advantages and disadvantages of the traditional power prediction method and optimal gradient method are firstly analyzed; then a novel power prediction method with high-precision power calculation, as we as an improved optimal gradient method are proposed. Finally, Simulink simulation analysis is carried out on the proposed MPP tracking strategy when the light intensity changes rapidly. The simulation results show that when the light intensity changes rapidly, the novel power prediction improvement is adopted. The optimal gradient method can not only eliminate the misjudgment phenomenon and oscillation phenomenon, but also the power calculation is more accurate. The introduction of the variable step factor can make the system output more power, which can well realize the fast tracking of MPP.
Sarcocystis Attenuati N. Sp. (Apicomplexa: Sarcocystidae) Infecting the Asian Gray Shrew, Crocidura Attenuata (Insectivora: Soricidae), in China
Authors: hu junjie , Sun Jun , Guo Yanmei , Zeng Hongxia , Zhang Yunzhi , Tao Jianping
Published: September 2021

Background: There are limited data on Sarcocystis in insectivores. The Asian gray shrew, Crocidura attenuata, is one of the most common species of insectivores in the family Soricidae distributed in South Asia and Southeast Asia. To date, Sarcocystis has never been recorded in this host.Methods: Tissues from 42 Asian gray shrews were collected in China in 2017 and 2018. Sarcocysts were observed using light (LM) and transmission electron microscopy (TEM). To complete the parasite life cycle, muscle tissues of the host infected with sarcocysts were force-fed to two beauty rat snakes, Elaphe taeniura. Individual sarcocysts from different Asian gray shrews and oocysts/sporocysts isolated from the small intestines and feces of the experimental snakes were selected for DNA extraction, and seven genetic markers, including two nuclear loci (18S rDNA and ITS1), three mitochondrial genes (cox1, cox3 and cytb), and two apicoplastic genes (rpoB and clpC), were amplified, sequenced and analyzed.Results: Sarcocysts were found in 17 of 42 (40.5%) Asian gray shrews. Under LM, the microscopic sarcocysts were exhibited saw-tooth-like protrusions measuring 3.3–4.5 μm. Ultrastructurally, the sarcocyst wall contained numerous lancet- or leaf-like villous protrusions, similar to type 9h. The experimental beauty rat snakes shed oocysts/sporcysts measuring 11.9–16.7 × 9.2–10.6 μm with a prepatent period of 10 to 11 days. Comparing these sequences with those previously deposited in GenBank revealed that the 18S rDNA sequences and cox1 sequences shared the highest similarity with those of S. scandentiborneensis recorded in tree shrews, Tuaia minor and T. tana (i.e., 97.6–98.3% and 100% identity, respectively). Phylogenetic analysis based on 18S rDNA, ITS1 or cox1 sequences revealed that this parasite formed an independent clade with Sarcocystis spp. that utilize small animals as intermediate hosts and snakes as the known or presumed definitive host. On the basis of morphological and molecular characteristics and host specificity, the parasite was proposed as a new species, named S. attenuati.Conclusions: Sarcocysts were recorded in Asian gray shrews for the first time. The sarcocysts were characterized morphologically and molecularly. The 18S rDNA and cox1 sequences of S. attenuati, named in the present study, shared the highest identities with those of S. scandentiborneensis. However, the sarcocysts of the two species of Sarcocystis were quite different under LM and TEM. Based on experimental infection, beauty rat snakes have been proven to be a definitive host of S. attenuati. As more species of Sarcocystis from insectivores and other small mammals are properly morphologically and molecularly characterized, we may gain a better understanding of the biodiversity, host specificity and evolution of Sarcocystis in the future.
Tumor Cell-Derived Exosomal hsa_circ_0017252 Suppresses the Tumorigenesis of Gastric Cancer Through Suppressing M2 Polarization of Macrophage
Authors: Song Jin , Xu Xiaolong , He Shasha , Wang Ning , Bai Yunjing , Li Bo , Zhang Shengsheng
Published: September 2021

Background: Gastric cancer (GC) is a source of global cancer death. MiR-17-5p is reported to regulate the tumorigenesis of GC. Meanwhile, hsa_circ_0017252 is known to be upregulated in GC. However, the relation between hsa_circ_0017252 and miR-17-5p in GC remains unclear. Methods: Cell viability, migration and invasion were tested by CCK-8 and transwell assay, respectively. Gene expressions were detected by RT-qPCR, and the protein levels in cells or exosomes were tested by western blot. The efficiency of exosomes isolation was investigated by transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA). Meanwhile, cell apoptosis was tested by flow cytometry. In vivo model was constructed to assess the function of MKN45 cells-derived exosomal hsa_circ_0017252 in GC. Results: Hsa_circ_0017252 was verified to be significantly downregulated in GC tissues. Hsa_circ_0017252 upregulation significantly decreased the viability and migration of GC cells, and hsa_circ_0017252 could bind with miR-17-5p. Additionally, exosomal hsa_circ_0017252 reversed the polarization of M2 macrophages, and the polarized macrophages decreased the GC cell invasion. Furthermore, exosomes with upregulated hsa_circ_0017252 suppressed the tumor growth of GC. Conclusion: Delivery of hsa_circ_0017252 by GC cells-derived exosomes inhibits the tumorigenesis of GC through reversing M2 polarization of macrophages. Thus, our finding might provide a new method for GC treatment.
Factors Related to Serum Lipids Using Multilevel Quantile Mixed Model: Analysis of Nationwide STEPs Survey 2016
Authors: Mohseni Parisa , Khalili Davood , Djalalinia Shirin , Farzadfar Farshad , Mehrabi Yadollah
Published: September 2021

Backgroundlipid disorder is a modifiable risk factor for diseases related to plaque formation in arteries such as heart attack, stroke and peripheral vascular diseases. Identifying related factors and diagnosis and treatment in time reduces the incidence of non - communicable diseases. The aim of this study was to determine factors associated with lipids based on a national survey data.MethodsData of 16757 individuals aged 25–64 years obtained from the Iranian national cross-sectional study of the risk factors of non-Communicable disease (STEPs) performed in 2016, through multi-stage random sampling, were analyzed. Because of clustered, hierarchical and skewed form of the data, factors related to total Cholesterol (TC), Triglycerides (TG), LDL-C, HDL-C, TG/HDL-C, TC/HDL-C, LDL-C/HDL-C were determined applying multilevel quantile mixed model. Parameters of the model were estimated on the basis of random effect of the province as well as urban or rural area for 10th, 25th, 50th, 75th and 90th quantiles. Statistical analyses were performed by R software version 4.0.2.ResultsSignificant relationship was found between age, BMI, waist circumference, diabetes, hypertension, smoking, physical activity, education level, and marital status with TC, LDL-C, HDL-C, LDL-C and LDL-C/HDL-C. With increasing BMI and WC, subjects had higher levels of serum lipids, especially in higher quantiles of lipid levels. Lipid levels were significantly increased among smokers and those with diabetes or hypertension. The random effects were also significant showing that there is a correlation between the level of lipids in provincial habitants as well as urban and rural areas.ConclusionThis study showed that the effect of each factor varies depending on the centiles of the lipids. Significant relationship was found between sociodemographic, Behaviors and anthropometric indices with lipid parameters.
Clinicopathological and Genetic Analyses of Small Cell Neuroendocrine Carcinoma of the Prostate: Histological Features for Accurate Diagnosis and Toward Future Novel Therapies Short Running Title: Characteristics of Prostatic Small Cell Neuroendocrine Carcinoma
Authors: Ida Arika , Okubo Yoichiro , Kasajima Rika , Washimi Kota , Sato Shinya , Yoshioka Emi , Osaka Kimito , Suzuki Takahisa , Yamamoto Yayoi , Yokose Tomoyuki , Kishida Takeshi , Miyagi Yohei
Published: September 2021

Differentiating small cell neuroendocrine carcinoma (SCNC) of the prostate from prostatic cancer with diffuse neuroendocrine (NE) differentiation based on morphological features alone can be challenging. Given that treatment strategies vary depending on histological type, accurate diagnosis is critical. This study firstly aimed to identify the accurate diagnostic factors for primary prostate NE tumors. Furthermore, the possibility of novel treatment strategies through genetic analysis is also an aim. Specifically, prostate biopsies conducted in our hospital between January 2017 and May 2020 were included. As a result seven cases of SCNC and four cases of prostatic cancer with diffuse NE differentiation were identified. No significant differences in serum neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), and prostate-specific antigen (PSA) levels were observed between SCNC and adenocarcinoma with diffuse NE differentiation. The Ki-67 labeling index was significantly higher and PSA immunoreactivity tended to be lower in SCNC. Genetic analysis did not detect any ALK mutations but confirmed several other mutations, including those of PIK3CA and TP53. In conclusion, given the heterogeneity in serum NE markers in SCNC, diagnosis based on these markers alone is difficult. A high Ki-67 labeling index and low PSA immunoreactivity may be useful for diagnosing, but p53 immunoreactivity is insufficient to distinguish these tumors. Although further studies are required to interpret the results of the genetic analysis involving ALK, PIK3CA, and TP53 mutations, the results of our genetic analysis suggest that PIK3CA mutations in SCNC of the prostate may provide a novel therapeutic strategy.
Seismic activity in the focus of the Uglegorsk earthquakes, Sakhalin Island in relevance to intensive development of coal deposits
Authors: Kostylev Dmitry , Boginskaya Natalya , Zakupin Alexander
Published: September 2021

Induced seismicity is an increase in seismic activity caused by the human engineering. An example of such activity is the mineral exploration, large water reservoirs construction, exploitation of underground oil and gas storages, etc. The authors studied the seismicity in the Uglegorsky district of Sakhalin region, where the Solntsevskoye brown coal field is located, which is the most promising in the island. Its area is over 100 sq. km, and productive strata of the Verkhneduiskaya formation with a thickness of up to 600 m contains 12 coal seams, 8 of which are working. Active mining of brown coal is carried out at the Solntsevsky coal mine, and blasting operations are performed on a large scale, that, as a result, does not exclude the relation of the seismic process to technogenic seismicity. The earthquake recurrence curves for two decades beginning from 2000 to the present were constructed in the work to compare the characteristics of the seismic regime in the studied area. The difference in the slope angle of recurrence graph during the period of 2011-2020 (the period of the most active development of the Solntsevsky coal mine) from the previous decade is quite significant. The maps of spatiotemporal distribution of seismic events epicenters in the vicinity of Solntsevsky coal mine are constructed. The contraction of zones of seismic events concentration to the mining areas, first of all to the Solntsevsky coal mine, have been found. Such a combination allows us to talk about an increase in seismicity of the region during the last years and change in its character from the natural to a mixed natural and technogenic. The focal mechanisms of the largest earthquakes occurred in the Uglegorsky district have been constructed in order to prove the change in seismicity character and reasons for the earthquake occurrence in the studied area. The mechanisms of seismic events of 2020 are classified as strike-slip faults, that is not character for the most earthquakes on the territory of Sakhalin Island. The authors made an attempt to determine the regularities of the parameters of the produced blasts and earthquakes through dynamic parameters of the seismic events foci by means of studying the frequency content of earthquakes and blasts in order to determine a corner frequency from the focal velocity spectrum.
WITHDRAWN: Plasma-based Endogenous Metabolomics Profiling of High-Risk Human Papillomavirus and Their Emerging Roles in the Progression of Cervical Cancer
Authors: Wang Qin , Xu Min , Chen Tingting , Chen Jing , Zhang Runjie , Qiu Jin
Published: September 2021

Objective: High-risk human papillomavirus (HR-HPV) is the main etiological factor for cervical cancer. Accumulating evidence has suggested that the active role of metabolites in the initiation and progression of cancers. This study was to explore the metabolic profiles of HR-HPV infection and their potential functions in cervical cancer.Methods: Non-targeted metabolomics approach was used to detect metabolic alterations in the plasma obtained from HPV-16 positive (HPV16 (+)), HPV-18 positive (HPV18 (+)) and HPV negative (CTL) individuals, followed by CCK8 experiment to detect the effect of different metabolites on the proliferation of Hela and GH354. A cell migration test then verified significant metabolites on the migration of Hela and GH354. Q RT-qPCR and western blot were used to detect malignant progression related mRNA and protein expression levels of cervical cancer.Results: HR-HPV groups shared 24 dysregulated metabolites (such as amino acids, ceramides, glycerophosphocholines). Further experiments showed ceramide species, including C8 inhibits cervical cancer cells proliferation and migration in vitro. In contrast, C12 significantly enhanced cervical cancer cells proliferation and migration in vitro. Protein and mRNA expressions indicated C8 and C12 were related to the malignant behavior of cervical cancer in vitro. The underlying mechanism demonstrated that C8 intervention inhibited proliferation and migration in cervical cancer cells via the MAPK/JNK signaling pathway, while C12 intervention promoted proliferation and migration in cervical cancer cells via the MAPK/ERK signaling pathway. These findings may contribute to the treatment of HR-HPV-induced cervical cancer by intervening in its initiation and progression.Conclusion: Our study shed some light on how metabolites influenced the relationship between HR-HPV oncogenic capability and metabolic phenotype change and identify species C8 and C12 as critical lipid metabolites that modulate cervical cancer cell’s function.