bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of crosstalk between STAT3 and mTOR signaling in driving sensitivity to chemotherapy in osteosarcoma cell lines
Authors: Wang Yi‐tian , Tang Fan , Hu Xin , Zheng Chuan‐xi , Gong Tao‐jun , Zhou Yong , Luo Yi , Min Li 
Published: July 2020

AbstractOsteosarcoma (OS) is a malignant bone neoplasm, mostly occurring in pediatric patients. OS is characterized by a highly aggressive and metastatically active tumor. Chemotherapy followed by surgical excision is the treatment of choice but is often associated with both chemoresistance and relapse. Hence, it is important to develop further understanding of OS pathogenesis and identify potential therapeutic targets. Both the signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) have been implicated in OS pathogenesis. Crosstalk between mTOR and STAT3 signaling has been shown to regulate hypoxia‐induced angiogenesis in other diseases. In this study, we determined using OS cell lines if there is a crosstalk between these two pathways and how that impacts sensitivity to treatment with Rapamycin. OS cell lines exhibited differential sensitivity to mTOR inhibitor Rapamycin. Evaluation of phosphorylated STAT3 showed that in Rapamycin‐sensitive 143B cells, the inhibitor decreased phosphorylation of STAT3 at Y705, but not at S727 whereas, in Rapamycin‐resistant U2OS cells, the inhibitor decreased S727 phosphorylation but not Y705. However, knockdown of STAT3 in U2OS cells made them sensitive to Rapamycin. Immunofluorescence (IF) analysis showed that mTOR is constitutively activated in the 143B cells but is suppressed in the U2OS cells, indicating that this might be their reason for being resistant to Rapamycin. Both cell lines were sensitive to treatment with the STAT3 inhibitor Napabucasin (NP). Treatment with NP inhibited STAT3 activation at Y705 and additionally inhibited mTOR activation, indicating crosstalk between STAT3 and mTOR signaling pathways. Rapamycin could effectively prevent lung metastasis in an orthotropic OS mice model using 143B cells. However, Rapamycin could not inhibit lung metastasis in mice injected with U2OS cells. The STAT3 inhibitor NP attenuated lung metastasis with the U2OS cells. Our results thus established yet undefined crosstalk of STAT3 and mTOR signaling pathways in OS and highlight the possibility of using mTOR inhibitors for treatment in patients with OS.
Test–Retest Reliability and Correlates of Vertebral Bone Marrow Lipid Composition by Lipidomics Among Children With Varying Degrees of Bone Fragility
Authors: Whitney Daniel G , Devlin Maureen J , Alford Andrea I , Modlesky Christopher M , Peterson Mark D , Li Ying , Caird Michelle S 
Published: July 2020

ABSTRACTThe reliability of lipidomics, an approach to identify the presence and interactions of lipids, to analyze the bone marrow lipid composition among pediatric populations with bone fragility is unknown. The objective of this study was to assess the test–retest reliability, standard error of measurement (SEM), and the minimal detectable change (MDC) of vertebral bone marrow lipid composition determined by targeted lipidomics among children with varying degrees of bone fragility undergoing routine orthopedic surgery. Children aged 10 to 19 years, with a confirmed diagnosis of adolescent idiopathic scoliosis (n = 13) or neuromuscular scoliosis and cerebral palsy (n = 3), undergoing posterior spinal fusion surgery at our institution were included in this study. Transpedicular vertebral body bone marrow samples were taken from thoracic vertebrae (T11, 12) or lumbar vertebrae (L1 to L4). Lipid composition was assessed via targeted lipidomics and all samples were analyzed in the same batch. Lipid composition measures were examined as the saturated, monounsaturated, and polyunsaturated index and as individual fatty acids. Relative and absolute test–retest reliability was assessed using the intraclass correlation coefficient (ICC), SEM, and MDC. Associations between demographics and index measures were explored. The ICC, SEM, and MDC were 0.81 (95% CI, 0.55–0.93), 1.6%, and 4.3%, respectively, for the saturated index, 0.66 (95% CI, 0.25–0.87), 3.5%, and 9.7%, respectively, for the monounsaturated index, and 0.60 (95% CI, 0.17–0.84), 3.6%, and 9.9%, respectively, for the polyunsaturated index. For the individual fatty acids, the ICC showed a considerable range from 0.04 (22:2n‐6) to 0.97 (18:3n‐3). Age was positively correlated with the saturated index (r2 = 0.36; p = 0.014) and negatively correlated with the polyunsaturated index (r2 = 0.26; p = 0.043); there was no difference in index measures by sex (p > 0.58). The test–retest reliability was moderate‐to‐good for index measures and poor to excellent for individual fatty acids; this information can be used to power research studies and identify measures for clinical or research monitoring. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
A theoretical study on the alkali metal carboxylate‐promoted L‐Lactide polymerization
Authors: Ozen Cihan , Satoh Toshifumi , Maeda Satoshi 
Published: July 2020

AbstractSodium acetate‐catalyzed L‐lactide polymerization reaction is a simple yet efficient reaction. It provides a robust system to produce poly(L‐lactide) in industrial scale. In this study, the mechanism of this reaction has been studied by means of computational chemistry tools based on the experimental results. Basically, the mechanism consists of two steps: lactide coordination and ring opening through O‐Acyl bond cleavage. Additionally, the effect of cation size and substituent on carboxylate moiety have been evaluated. The calculations indicate that the larger cation leads to faster reactions. Moreover, the stronger electron‐donating group on carboxylate moiety accelerates the reaction rates. To obtain further insights, an orbital analysis has been also carried out. Our calculations are consistent with experimental findings and clarify underlying mechanistic features of the present reaction.
Comparison of dentin penetration ability of different root canal sealers used with different obturation methods
Authors: Turkyilmaz Ali , Erdemir Ali 
Published: July 2020

AbstractThis in vitro study aimed to investigate the tubular penetration depth of four different sealers used with two different obturation methods in the apical, middle, and coronal root canal dentin. Eighty‐four single‐rooted teeth were instrumented until the F4 ProTaper universal rotary file and filled with AH26, AH Plus (Dentsply, DeTrey, Konstanz, Germany), RealSeal (SybronEndo, Orange, CA), and MTA Fillapex (Angelus, Londrina, Brazil) using cold lateral condensation (CLC) and single‐cone (SC) obturation techniques. Thereafter, the roots were sectioned longitudinal and prepared for scanning electron microscope evaluation. The maximum and minimum sealers penetration depth into dentinal tubules at the apical, middle, and coronal regions and the average depth of sealer penetration were calculated. The data was statistically analyzed two‐way ANOVA and post hoc Tukey and Dunnett tests and independent samples t test using maximum mean values. There was no statistically difference between the obturation methods (p > .05). When the sealers are evaluated within themselves AH26 was affected by obturation methods significantly (p < .05). Also the results revealed a significant difference between root regions (p < .05). AH26 and RealSeal root canal sealers had the highest penetration values with CLC and SC obturation techniques, respectively. The obturation method did not affect the penetration amount of root canal sealers. RealSeal root canal sealer performed better penetration ability than the other sealers. Apical third of the root in all groups showed lowest penetration depth.
A digital image analysis study on the disintegration kinetics of reticular fibers in the ethylene glycol‐induced rat liver tissue
Authors: Ünver Saraydin Serpil , Saraydin Dursun , Şahin İnan Zeynep Deniz 
Published: July 2020

AbstractEthylene glycol (EG), the raw material of polyethylenterephthalate, which is the most consumed plastic in the world, has low toxicity, but its metabolites are toxic. EG metabolites can cause acidosis, fibrosis, and eventually cirrhosis in the liver. This study aimed to investigate the effect of EG on rat liver and to determine the quantitative values of the disintegration of reticular fibers (RF) in the liver with the dose duration and to investigate the changes by digital image analysis (DIA). For this purpose, Wistar albino rats were divided into control, and five different daily experimental groups. The control group received saline, and the experimental groups received EG. At the end of experiments, liver tissues of all euthanized rats were removed, and sections were taken, and RF was shown by silver staining. It was observed that the RF fragments in the experimental groups were less than the control group. DIA of RF fragments was then performed with Olympus cellSensDimension 1.15 software and number, area, and ROI% values of the fragments were determined. Statistical analysis revealed that there was a significant difference between control and all experimental groups. RF fragments showed first‐order disintegration kinetics, mean disintegration rate constant, and half‐time values were 0.1 day−1 and 7 days, respectively. Consequently, the digital image analysis approach can be a useful tool for the biologist, pathologist, fibrosis‐cirrhosis specialist, and computer scientist to understand the effects of toxic chemicals in the liver and analyze reticular fiber disintegration.
Circ_0000105 promotes liver cancer by regulating miR‐498/PIK3R1
Authors: Sun Yanni , Sun Xiuxiang , Huang Qingxian 
Published: July 2020

AbstractBackgroundA growing number of studies demonstrate that circular RNA (circRNA) has a prominent role in the regulation of numerous biological behaviors of tumor cells. The present study aimed to investigate the expression, function and molecular mechanisms of circ_0000105 in liver cancer.MethodsA quantitative real‐time polymerase chain reaction (qRT‐PCR) was utilized to obtain the expressions of circ_0000105 and miR‐498 in liver cancer tissues and cells. The association between the expression level of circ_0000105 and the clinicopathological characteristics of liver cancer patients was analyzed. qRT‐PCR and western blotting were utilized to investigate the expression of phosphoinositide‐3‐kinase regulatory subunit 1 (PIK3R1) in cells. Cell counting kit‐8, bromodeoxyuridine and flow cytometry assays were utilized to determine liver cancer cell proliferation and apoptosis, respectively. Bioinformatics, a luciferase reporter gene experiment and a RNA immunoprecipitation experiment were conducted to predict and confirm the targeting correlation of circ_0000105 and miR‐498, as well as miR‐498 and PIK3R1.ResultsCirc_0000105 was highly expressed in liver cancer tissues and cell lines. Moreover, its high expression was associated with an increase in the T stage of liver cancer patients and a low degree of tumor differentiation. Circ_0000105 overexpression promoted liver cancer cell proliferation and inhibited apoptosis, whereas knocking down circ_0000105 triggered the opposite effect. miR‐498 was a downstream target of circ_0000105, inhibiting liver cancer cell proliferation and promoting apoptosis. Mechanistically, circ_0000105 indirectly up‐regulated the expression of PIK3R1 by adsorbing miR‐498.ConclusionsCirc_0000105 plays a cancer‐promoting role in liver cancer by regulating the miR‐498/PIK3R1 axis.
Rituximab maintenance significantly reduces early follicular lymphoma progressions in patients treated with frontline R‐CHOP
Authors: Procházka Vít , Belada David , Janíková Andrea , Benešová Kateřina , Mociková Heidi , Ďuraš Juraj , Pirnos Jan , Kopečková Kateřina , Campr Vít , Fürst Tomáš , Pytlík Robert , Sýkorová Alice , Michalka Jozef , Dlouhá Jitka , Papajík Tomáš , Trněný Marek 
Published: July 2020

AbstractTwenty percent of patients with high‐tumor‐burden (HTB) follicular lymphoma (FL) develop progression/relapse of disease (POD) within 24 months of frontline immunochemotherapy. Unfortunately, about 50% of these patients die within 5 years since POD event. Rituximab maintenance was proven to reduce relapse rate in responding FL, but its role on preventing POD was not defined. We analyzed 1360 HTB‐FL patients from the Czech Lymphoma Study Group registry treated with frontline rituximab‐containing regimen. Of those, 950 cases received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) and achieved complete or partial remission: 712 patients received rituximab maintenance (MAINT) and 238 were a historical observational cohort (OBS). We have proposed a modified POD24 (mPOD24) endpoint for the chemosensitive patients calculated from the end‐of‐induction (EOI). Survival rates since EOI were as follows: 5‐year overall survival (OS) 86.2% versus 94.5% in the OBS and MAINT groups, respectively (P < .001) and 5‐year progression‐free survival 58.5% (OBS) and 75.4% (MAINT) (P < .001). The Cox proportional hazards model showed a decrease in mPOD24 incidence in the MAINT group with the overall hazard rate reduced by 56% (hazard ratio = 0.44; P < .001). The cumulative incidence of mPOD24 was reduced from 24.1% in OBS to 10.1% in MAINT (P < .001). Comparison of non‐mPOD24 cases showed OS similar to that in the general population. Rituximab maintenance given after R‐CHOP resulted in a 2.4‐fold reduction in mPOD24 incidence. Once the non‐POD24 status is achieved, FL does not shorten the patients’ life expectancy.
Intra‐day variability of temperature and its near‐surface gradient with elevation over mountainous terrain: Comparing MODIS land surface temperature data with coarse and fine scale near‐surface measurements
Authors: Collados‐Lara Antonio‐Juan , Fassnacht Steven R. , Pulido‐Velazquez David , Pfohl Anna K.D. , Morán‐Tejeda Enrique , Venable Niah B.H. , Pardo‐Igúzquiza Eulogio , Puntenney‐Desmond Kira 
Published: July 2020

AbstractWhere land surface air temperature data are not available, satellite land surface temperature are used. However, the coarse spatial resolution of satellite‐derived products may yield errors at the local scale. This work shows the differences between the MODIS Land Surface Temperature and Emissivity (MOD11A1) product and ground measurements at two different scales. We used data from 21 SNOTEL stations across the northern Front Range of Colorado to represent the coarse scale and 17 iButton temperature sensors across the Colorado State University Mountain Campus to represent the fine scale. We found significant differences in the temperature and its changes with elevation for the two spatial scales. At the fine scale, cold air drainage can induce an inversion of the temperature gradient with elevation. A higher correlation was found during the nighttime at the fine scale, while, at the coarse scale, higher correlations were observed during the daytime. On windy nights, temperatures do not cool as much as on calmer nights, and the coarse scale near‐surface temperature gradient with elevation persists, though the fine scale inversions do not develop. The near‐surface temperature gradients with elevation based on the MODIS pixels are similar to the ground‐based data at the coarse scale but not at the fine scale. Thus, one must be cautious in selecting the near‐surface temperature gradients with elevation for mountainous terrain when different scales are considered, and a proper validation of satellite products is necessary prior to their use to avoid the propagation of uncertainties.
Knee fibrosis is associated with the development of osteoarthritis in a murine model of tibial compression
Authors: Wang Mengying , Lessard Samantha G. , Singh Purva , Pannellini Tania , Chen Tony , Rourke Brennan J. , Chowdhury Luvana , Craveiro Vinicius , Sculco Peter K. , van der Meulen Marjolein C. H. , Otero Miguel 
Published: July 2020

AbstractFibrosis in the synovium and infrapatellar fat pad (IFP) is frequently observed in knee osteoarthritis (OA) and is often correlated with joint pain and stiffness. However, the mechanisms underpinning the development of knee fibrosis in OA are relatively poorly understood. In this study, we used a combination of histological, immunohistochemical, and multiplex gene expression analyses to characterize the fibrosis that develops in a mouse model of load‐induced OA. Histological evaluation showed the time‐dependent development of fibrosis in the synovium, capsule, and IFP of loaded limbs of male 11‐week‐old mice. The development of load‐induced fibrosis was accompanied primarily by proliferation, expansion, and activation of the stromal compartment, and by increased macrophage presence evidenced by increased F4/80 and MAC2 positive immunostaining. The presence of B and T‐cells was minimal in both control and loaded limbs, but CD3‐positive immunostaining was significantly higher in C57BL/6J at 2 weeks after loading, indicating an increased presence of T‐cells. Using NanoString gene expression analyses of human and mouse tissues, we found that mice subjected to cyclic loading recapitulated the gene expression profile observed in human fibrotic tissues, including increased expression of collagen genes. Together, our results indicate that this well‐controlled nonsurgical mouse model can be used to study the mechanisms underpinning the development of knee fibrosis, and potentially to test targeted strategies to prevent the development of fibrosis and stiffness of the knee.
Novel Adaptation of a Validated Tactile Aesthesiometer to Evaluate Laryngopharyngeal Sensation
Authors: Strohl Madeleine P. , Young VyVy N. , Dwyer Christopher D. , Bhutada Abhishek , Crawford Ethan , Chang Jolie L. , Rosen Clark A. , Cheung Steven W. 
Published: July 2020

ObjectivesTo evaluate laryngopharyngeal sensation at specific subsites using a novel adaptation of a buckling force aesthesiometer for delivery of calibrated tactile stimuli.Study DesignCross‐sectional.MethodsTwenty‐two healthy adults (12 men, 10 women) were tested for responses to tactile forces, using 30‐mm 6‐0, 5‐0, and 4‐0 nylon monofilaments to map sensation of the aryepiglottic (AE) fold, lateral pyriform sinus (PS), and medial PS bilaterally. The outcome measures were the laryngeal adductor reflex (LAR) and patient reported rating of perceptual strength.ResultsRates of triggered LAR response grew monotonically with increasing tactile force at a mean (SD) stimulus duration of 663 (164) msec across all three subsites. The AE fold and medial PS had similar profiles and were the most responsive, while the lateral PS was the least responsive. Low force (6‐0) response rate was ≤14% for all subsites. High force (4‐0) response rate was 91% for AE fold and medial PS, and 23% for lateral PS. The perceptual strength gradient was in the lateral to medial trajectory.ConclusionNormative data for LAR response rates to low, medium, and high stimulation forces will be useful to assess sensory dysfunction in a variety of laryngopharyngeal disorders, including aspiration, dysphagia, chronic cough, and spasmodic dysphonia. In turn, that information will guide the creation of innovative treatments. LAR response profiles to low and high force stimuli will inform the development of screening tools to diagnose laryngopharyngeal hypersensitivity and hyposensitivity conditions.Level of Evidence3b Laryngoscope, 131:1324–1331, 2021
Thermally Targeted p50 Peptide Inhibits Proliferation and Induces Apoptosis of Breast Cancer Cell Lines
Authors: Thomas Emily , Dragojevic Sonja , Price Amira , Raucher Drazen 
Published: July 2020

AbstractThe application of rationally designed therapeutic peptides (TP) may improve outcomes in cancer treatment. These peptides hold the potential to directly target proliferative pathways and stimulate cell arrest or death pathways. Elastin‐like polypeptide (ELP) is an elastin derived biopolymer that undergoes a thermally mediated phase transition. This study employs p50, a nuclear localization sequence derived peptide that inhibits the activation of NFκB and is implicated in cancer cell survival and metastasis. In order to effectively delivery p50, it is conjugated to SynB1‐ELP1, a thermally responsive macromolecular carrier. By applying an external heat source, mild hyperthermic conditions (41 °C) induce aggregation and therefore can be used to specifically target ELP to solid tumors in cancer therapy. The addition of a cell penetrating peptide (CPP) to the N‐terminus of the macromolecular carrier enhances the cellular uptake and directs the subcellular localization of the bioactive peptide. The novel TP, p50, inhibits proliferation and induces apoptosis of breast cancer cells by blocking the intranuclear import of NFκB. By expanding the repertoire of oncogenic targets, CPPs, and ELP carrier sizes, ELP‐based polypeptides may be modulated to optimize the delivery of these novel therapies and allow for the flexibility to create individualized cancer therapies.
Well‐posedness of degenerate fractional integro‐differential equations in vector‐valued functional spaces
Authors: Bu Shangquan , Cai Gang 
Published: July 2020

AbstractWe study the well‐posedness of the fractional degenerate integro‐differential equations
in Lebesgue–Bochner spaces and Besov spaces , where A, B and M are closed linear operators on a Banach space X satisfying , , and . We completely characterize the well‐posedness of in the above vector‐valued function spaces on by using operator‐valued Fourier multiplier. We also give an example that our abstract results may be applied.
Missed diagnoses: Clinically relevant lessons learned through medical mysteries solved by the Undiagnosed Diseases Network
Authors: Cope Heidi , Spillmann Rebecca , Rosenfeld Jill A. , Brokamp Elly , Signer Rebecca , Schoch Kelly , Glanton Emily , Sullivan Jennifer A. , Macnamara Ellen , Lincoln Sharyn , Golden‐Grant Katie ,   Undiagnosed Diseases Network, Orengo James P. , Clark Gary , Burrage Lindsay C. , Posey Jennifer E. , Punetha Jaya , Robertson Amy , Cogan Joy , Phillips John A. , Martinez‐Agosto Julian , Shashi Vandana 
Published: July 2020

AbstractBackgroundResources within the Undiagnosed Diseases Network (UDN), such as genome sequencing (GS) and model organisms aid in diagnosis and identification of new disease genes, but are currently difficult to access by clinical providers. While these resources do contribute to diagnoses in many cases, they are not always necessary to reach diagnostic resolution. The UDN experience has been that participants can also receive diagnoses through the thoughtful and customized application of approaches and resources that are readily available in clinical settings.MethodsThe UDN Genetic Counseling and Testing Working Group collected case vignettes that illustrated how clinically available methods resulted in diagnoses. The case vignettes were classified into three themes; phenotypic considerations, selection of genetic testing, and evaluating exome/GS variants and data.ResultsWe present 12 participants that illustrate how clinical practices such as phenotype‐driven genomic investigations, consideration of variable expressivity, selecting the relevant tissue of interest for testing, utilizing updated testing platforms, and recognition of alternate transcript nomenclature resulted in diagnoses.ConclusionThese examples demonstrate that when a diagnosis is elusive, an iterative patient‐specific approach utilizing assessment options available to clinical providers may solve a portion of cases. However, this does require increased provider time commitment, a particular challenge in the current practice of genomics.