bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doxorubicin‐induced skeletal muscle atrophy: Elucidating the underlying molecular pathways
Authors: Hiensch Anouk E. , Bolam Kate A. , Mijwel Sara , Jeneson Jeroen A. L. , Huitema Alwin D. R. , Kranenburg Onno , van der Wall Elsken , Rundqvist Helene , Wengstrom Yvönne , May Anne M. 
Published: October 2019

AbstractAimLoss of skeletal muscle mass is a common clinical finding in cancer patients. The purpose of this meta‐analysis and systematic review was to quantify the effect of doxorubicin on skeletal muscle and report on the proposed molecular pathways possibly leading to doxorubicin‐induced muscle atrophy in both human and animal models.MethodsA systematic search of the literature was conducted in PubMed, EMBASE, Web of Science and CENTRAL databases. The internal validity of included studies was assessed using SYRCLE’s risk of bias tool.ResultsTwenty eligible articles were identified. No human studies were identified as being eligible for inclusion. Doxorubicin significantly reduced skeletal muscle weight (ie EDL, TA, gastrocnemius and soleus) by 14% (95% CI: 9.9; 19.3) and muscle fibre cross‐sectional area by 17% (95% CI: 9.0; 26.0) when compared to vehicle controls. Parallel to negative changes in muscle mass, muscle strength was even more decreased in response to doxorubicin administration. This review suggests that mitochondrial dysfunction plays a central role in doxorubicin‐induced skeletal muscle atrophy. The increased production of ROS plays a key role within this process. Furthermore, doxorubicin activated all major proteolytic systems (ie calpains, the ubiquitin‐proteasome pathway and autophagy) in the skeletal muscle. Although each of these proteolytic pathways contributes to doxorubicin‐induced muscle atrophy, the activation of the ubiquitin‐proteasome pathway is hypothesized to play a key role. Finally, a limited number of studies found that doxorubicin decreases protein synthesis by a disruption in the insulin signalling pathway.ConclusionThe results of the meta‐analysis show that doxorubicin induces skeletal muscle atrophy in preclinical models. This effect may be explained by various interacting molecular pathways. Results from preclinical studies provide a robust setting to investigate a possible dose‐response, separate the effects of doxorubicin from tumour‐induced atrophy and to examine underlying molecular pathways. More research is needed to confirm the proposed signalling pathways in humans, paving the way for potential therapeutic approaches.
Likert vs PI‐RADS v2: a comparison of two radiological scoring systems for detection of clinically significant prostate cancer
Authors: Khoo Christopher C. , Eldred‐Evans David , Peters Max , Bertoncelli Tanaka Mariana , Noureldin Mohamed , Miah Saiful , Shah Taimur , Connor Martin J. , Reddy Deepika , Clark Martin , Lakhani Amish , Rockall Andrea , Hosking‐Jervis Feargus , Cullen Emma , Arya Manit , Hrouda David , Qazi Hasan , Winkler Mathias , Tam Henry , Ahmed Hashim U. 
Published: October 2019

ObjectiveTo compare the clinical validity and utility of Likert assessment and the Prostate Imaging Reporting and Data System (PI‐RADS) v2 in the detection of clinically significant and insignificant prostate cancer.Patients and MethodsA total of 489 pre‐biopsy multiparametric magnetic resonance imaging (mpMRI) scans in consecutive patients were subject to prospective paired reporting using both Likert and PI‐RADS v2 by expert uro‐radiologists. Patients were offered biopsy for any Likert or PI‐RADS score ≥4 or a score of 3 with PSA density ≥0.12 ng/mL/mL. Utility was evaluated in terms of proportion biopsied, and proportion of clinically significant and insignificant cancer detected (both overall and on a ‘per score’ basis). In those patients biopsied, the overall accuracy of each system was assessed by calculating total and partial area under the receiver‐operating characteristic (ROC) curves. The primary threshold of significance was Gleason ≥3 + 4. Secondary thresholds of Gleason ≥4 + 3, Ahmed/UCL1 (Gleason ≥4 + 3 or maximum cancer core length [CCL] ≥6 or total CCL≥6) and Ahmed/UCL2 (Gleason ≥3 + 4 or maximum CCL ≥4 or total CCL ≥6) were also used.ResultsThe median (interquartile range [IQR]) age was 66 (60–72) years and the median (IQR) prostate‐specific antigen level was 7 (5–10) ng/mL. A similar proportion of men met the biopsy threshold and underwent biopsy in both groups (83.8% [Likert] vs 84.8% [PI‐RADS v2]; P = 0.704). The Likert system predicted more clinically significant cancers than PI‐RADS across all disease thresholds. Rates of insignificant cancers were comparable in each group. ROC analysis of biopsied patients showed that, although both scoring systems performed well as predictors of significant cancer, Likert scoring was superior to PI‐RADS v2, exhibiting higher total and partial areas under the ROC curve.ConclusionsBoth scoring systems demonstrated good diagnostic performance, with similar rates of decision to biopsy. Overall, Likert was superior by all definitions of clinically significant prostate cancer. It has the advantages of being flexible, intuitive and allowing inclusion of clinical data. However, its use should only be considered once radiologists have developed sufficient experience in reporting prostate mpMRI.
Waterjet Ablation Therapy for Endoscopic Resection of prostate tissue trial (WATER) vs WATER II: comparing Aquablation therapy for benign prostatic hyperplasia in 30–80 and 80–150 mL prostates
Authors: Nguyen David‐Dan , Barber Neil , Bidair Mo , Gilling Peter , Anderson Paul , Zorn Kevin C. , Badlani Gopal , Humphreys Mitch , Kaplan Steven , Kaufman Ronald , So Alan , Paterson Ryan , Goldenberg Larry , Elterman Dean , Desai Mihir , Lingeman Jim , Roehrborn Claus , Bhojani Naeem 
Published: October 2019

ObjectiveTo compare the outcomes of Aquablation in 30–80 mL prostates with those in 80–150 mL prostates. Surgical options, especially with short learning curves, are limited when treating large prostates for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). Aquablation (AquaBeam System, PROCEPT BioRobotics Inc., Redwood City, CA, USA) could solve this issue with global reproducibility, independent of prostate volume.Patients and MethodsWaterjet Ablation Therapy for Endoscopic Resection of prostate tissue (WATER [W‐I]; NCT02505919) is a prospective, double‐blind, multicentre, international clinical trial comparing Aquablation and transurethral resection of the prostate (TURP) for the treatment of LUTS/BPH in prostates between 30 and 80 mL. WATER II (W‐II; NCT03123250) is a prospective, multicentre, single‐arm international clinical trial of Aquablation in prostates between 80 and 150 mL. We compare baseline parameters and 12‐month outcomes in 116 W‐I and 101 W‐II study patients. Students’ t‐test or Wilcoxon tests were used for continuous variables and Fisher’s test for binary variables.ResultsThe mean (SD) operative time was 33 (17) and 37 (13) min in W‐I and W‐II, respectively. Actual treatment time was 4 and 8 min in W‐I and W‐II, respectively. The mean change in the International Prostate Symptom Score was substantial averaging (at 12 months) 15.1 in W‐I and 17.1 in W‐II (P = 0.605). By 3 months, Clavien–Dindo grade ≥II events occurred in 19.8% of W‐I patients and 34.7% of W‐II patients (P = 0.468).ConclusionAquablation clinically normalises outcomes between patients with 30–80 mL prostates and patients with 80–150 mL prostates treated for LUTS/BPH, with an expected increase in the risk of complications in larger prostates. Long‐term outcomes of procedure durability are needed.
Tumor‐suppressive circular RNAs: Mechanisms underlying their suppression of tumor occurrence and use as therapeutic targets
Authors: Li Zhe , Ruan Yao , Zhang Haiyan , Shen Yijing , Li Tianwen , Xiao Bingxiu 
Published: October 2019

AbstractCircular RNAs (circRNAs) have a covalently closed circular conformation and are structurally stable. Those circRNAs with tumor‐suppressive properties play an important role in tumorigenesis and metastasis and thus may be used as therapeutic targets of cancers. Herein, we review the current understanding of the classification of circRNAs and summarize the functions and mechanisms of circRNAs that have tumor‐suppressive roles in various cancers, including liver cancer (circARSP91, circADAMTS13, circADAMTS14, circMTO1, hsa_circ_0079299, and circC3P1), bladder cancer (circFNDC3B, circITCH, circHIPK3, circRNA‐3, cdrlas, and circLPAR1), gastric cancer (circLARP4, circYAP1, hsa_cric_0000096, hsa_circ_0000993, and circPSMC3), breast cancer (circ_000911, hsa_circ_0072309, and circASS1), lung cancer (hsa_circ_0000977, circPTK2, circ_0001649, hsa_circ_100395, and circ_0006916), glioma (circ_0001946, circSHPRH, and circFBXW7), and colorectal cancer (circITGA7 and hsa_circ_0014717). Thanks to their structural stability, these tumor‐suppressive circRNAs may be used as potential and potent therapeutic targets. Moreover, we propose a new method for the classification of circRNAs. Based on whether they can be translated, circRNAs can be divided into noncoding circRNAs and coding circRNAs.
Serum microRNA profile enables preoperative diagnosis of uterine leiomyosarcoma
Authors: Yokoi Akira , Matsuzaki Juntaro , Yamamoto Yusuke , Tate Keisei , Yoneoka Yutaka , Shimizu Hanako , Uehara Takashi , Ishikawa Mitsuya , Takizawa Satoko , Aoki Yoshiaki , Kato Ken , Kato Tomoyasu , Ochiya Takahiro 
Published: October 2019

AbstractUterine leiomyosarcoma (ULMS) is the major subtype of uterine sarcoma (US) and contributes to uterine cancer deaths. Although preoperative diagnosis of US remains challenging, frequent application of laparoscopic surgery for benign uterine leiomyomas (ULM) requires precise exclusion of US. MicroRNAs are stably present in the bloodstream, and the application of circulating miRNAs as disease biomarkers has been recognized. In the present study, we aimed to identify diagnostic biomarkers for distinguishing US from ULM by focusing on circulating miRNAs. All serum samples were collected preoperatively between 2009 and 2017, and all cases were histopathologically diagnosed. Whole miRNA profiles were obtained using a miRNA microarray. By analyzing expression levels of the miRNAs, candidate miRNAs were selected based on diagnostic performance in discriminating US from ULM, and a diagnostic model was then constructed. A total of 90 serum samples were analyzed, and clustering analyses revealed that the profiles of ULMS were distinct from those of controls. Based on leave‐one‐out cross‐validation, seven miRNAs were selected as biomarker candidates. Based on model construction, the optimal model consisted of two miRNAs (miR‐1246 and miR‐191‐5p), with an area under the receiver operating characteristic curve (AUC) for identifying ULMS of 0.97 (95% confidence interval [CI], 0.91‐1.00). In contrast, serum lactate dehydrogenase had an AUC of only 0.64 (95% CI, 0.34‐0.94). Seven serum miRNAs with high diagnostic performance for preoperative US screening were detected, and a promising diagnostic model for ULMS was generated.
A comparison of open, laparoscopic and robotic total mesorectal excision: trial sequential analysis and network meta‐analysis
Authors: Zheng B. , Zhang X. , Wang X. , Ge L. , Wei M. , Bi L. , Deng X. , Wang Q. , Li J. , Wang Z. 
Published: October 2019

AbstractAimTotal mesorectal excision (TME) for rectal cancer can be achieved by employing open (OpTME), laparoscopic (LaTME) and robotic (RoTME) approaches but which of these has the best outcome? The aim of present study is to identify the most effective technique for rectal cancer by comparing all outcomes.MethodsRandomized controlled trials (RCTs) which compared at least two TME strategies were identified by literature search of electronic databases of articles published to June 2018. Network meta‐analysis with trial sequential analysis was performed using a frequentist approach with random‐effects meta‐analysis.Data collection and analysisWe conducted a systematic search of PubMed, EmBase, the Cochrane Library, CNKI, and Web of Science. Titles and abstracts of the retrieved publications were independently and blindly assessed by two authors.ResultsTwenty‐two RCTs with 4882 rectal cancer patients were included in this analysis. The trial sequential analysis demonstrated that the cumulative Z‐curve crossed either the traditional boundary or the trial sequential monitoring boundaries, suggesting that OpTME resulted in a more complete TME specimen than LaTME (relative risk 1.05, 95% confidence interval 1.01–1.08). Network meta‐analysis showed there was no significant difference in the other comparisons. Based on the P score of completeness of the TME specimen and circumferential resection margin positivity, the best technique was OpTME, followed by RoTME and then LaTME. However, this order was reversed when complications and mortality were considered. RoTME led to better lymph node harvest.ConclusionsAlthough OpTME may give better pathological specimens, minimally invasive techniques may have advantages when considering lymph node harvest, complications and mortality. More RCTs are needed to determine which technique actually gives the best chance of survival.
IL‐7–Mediated IL‐7R‐JAK3/STAT5 signalling pathway contributes to chemotherapeutic sensitivity in non–small‐cell lung cancer
Authors: Shi Lin , Xu Zhaozhong , Yang Qiong , Huang Yuanyuan , Gong Yuxin , Wang Fang , Ke Bin 
Published: October 2019

AbstractObjectivesThe chemotherapy drug resistance is a major challenge for non‐small‐cell lung cancer (NSCLC) treatment. Combination of immunotherapy and chemotherapy has shown promise for cancer. The goal of this study was to evaluate the anti‐tumour efficacy of interleukin‐7 (IL‐7) combining cisplatin against NSCLC.Materials and MethodsCell proliferation was analysed using CCK‐8 assay, EdU proliferation assay and colony‐forming assay. Cell apoptosis was evaluated using HOECHST 33342 assay and flow cytometry. The protein expression levels were analysed by Western blot. The blocking antibody against the IL‐7 receptor and the inhibitors of STAT5 and JAK3 were used to investigate the pathway involved. A xenograft model was established to assess the anti‐tumour efficacy of IL‐7 combining cisplatin in vivo.ResultsHere we found IL‐7R was increased in A549/DDP cells compared with A549 cells. The block of IL‐7R reversed the inhibitory effects of IL‐7 combined with cisplatin and decreased the numbers of apoptosis cells induced by treatment of IL‐7 combined with cisplatin. The JAK3 inhibitor and STAT5 inhibitor were used to identify the pathway involved. The results showed that JAK3/STAT5 pathway was involved in enhancing role of cisplatin sensitivity of NSCLC cells by IL‐7. In vivo, cisplatin significantly inhibited tumour growth and IL‐7 combined with cisplatin achieved the best therapeutic effect.ConclusionTogether, IL‐7 promoted the sensitivity of NSCLC cells to cisplatin via IL‐7R‐JAK3/STAT5 signalling pathway.
Target‐Mediated Drug Disposition Pharmacokinetic/Pharmacodynamic Model‐Informed Dose Selection for the First‐in‐Human Study of AVB‐S6‐500
Authors: Bonifacio Laura , Dodds Michael , Prohaska David , Moss Aaron , Giaccia Amato , Tabibiazar Ray , McIntyre Gail 
Published: October 2019

AVB‐S6‐500 neutralized growth arrest‐specific 6 (GAS6) protein and effectively inhibited AXL signaling in preclinical cancer models. A target‐mediated drug disposition (TMDD) pharmacokinetic/pharmacodynamic (PK/PD) model was used to select first‐in‐human (FIH) doses for AVB‐S6‐500 based on predicted target (GAS6) suppression in the clinic. The effect of TMDD on AVB‐S6‐500 clearance was incorporated into a standard two‐compartment model, providing parallel linear and nonlinear clearance. Observed AVB‐S6‐500 and GAS6 concentration data in cynomolgus monkeys and relevant interspecies differences were used to predict the PK (serum concentration)/PD (GAS6 suppression) relationship in humans. Human exposure and GAS6 suppression were simulated for the proposed FIH doses of 1, 2.5, 5, and 10 mg/kg. A dose of 1 mg/kg was selected to target GAS6 suppression for 2 weeks in the initial healthy volunteer study. The cynomolgus monkey:human ratios for the highest proposed FIH dose were anticipated to yield more than a 10‐fold margin to the nonclinical no observed adverse event level while maintaining > 90% GAS6 suppression. In human subjects, the first dose (1 mg/kg) model‐projected and clinically observed maximal concentration (Cmax) was within 10% of predicted; repeat dosing at 5 mg/kg was within 1% (Cmax) and 45% (area under the serum concentration‐time curve from time 0 to end of dosing interval) of predicted. Predicted GAS6 suppression duration of 14 days was accurate for the 1 mg/kg dose. A PK/PD model expedited clinical development of AVB‐S6‐500, minimized exposure of patients with cancer to subtherapeutic doses, and rationally guided the optimal dosing in patients.
First demonstration of effective spatial training for near transfer to spatial performance and far transfer to a range of mathematics skills at 8 years
Authors: Gilligan Katie A. , Thomas Michael S. C. , Farran Emily K. 
Published: October 2019

AbstractThere is evidence that spatial thinking is malleable, and that spatial and mathematical skills are associated (Mix et al. [2016] Journal of Experimental Psychology: General, 145, 1206; Mix et al. [2017] Journal of Cognition and Development, 18, 465; Uttal et al. [2013] Psychological Bulletin, 139, 352). However, few studies have investigated transfer of spatial training gains to mathematics outcomes in children, and no known studies have compared different modes of spatial instruction (explicit vs. implicit instruction). Based on a sample of 250 participants, this study compared the effectiveness of explicit and implicit spatial instruction in eliciting near transfer (to the specific spatial skills trained), intermediate transfer (to untrained spatial skills) and far transfer (to mathematics domains) at age 8. Spatial scaling and mental rotation skills were chosen as training targets as previous studies have found, and proposed explanations for, associations between these skills and mathematics in children of this age (Journal of Experimental Psychology: General, 145, 2016 and 1206). In this study, spatial training led to near, intermediate and far transfer of gains. Mental visualization and proportional reasoning were proposed to explain far transfer from mental rotation and spatial scaling skills respectively. For most outcomes, except for geometry, there was no difference in the effectiveness of implicit (practice with feedback) compared to explicit instruction (instructional videos). From a theoretical perspective, the study identified a specific causal effect of spatial skills on mathematics skills in children. Practically, the results also highlight the potential of instructional videos as a method of introducing spatial thinking into the classroom.
IGFBP5 promotes angiogenic and neurogenic differentiation potential of dental pulp stem cells
Authors: Li Jing , Diao Shu , Yang Haoqing , Cao Yangyang , Du Juan , Yang Dongmei 
Published: October 2019

AbstractDental stem cells for dental pulp regeneration have become a new strategy for pulpitis treatment. Angiogenesis and neurogenesis play a vital role in the pulp‐dentin complex regeneration, and appropriate growth factors will promote the process of angiogenesis and neurogenesis. Insulin‐like growth factor‐binding protein 5 (IGFBP5) is involved in the regulation of tooth growth and development. A previous study showed that IGFBP5 enhanced osteo/odontogenic differentiation of dental stem cells. Our research intends to reveal the function of IGFBP5 in the angiogenic and neurogenic differentiation of human dental stem cells. Human dental pulp stem cells (DPSCs) were used in the present study. Lentiviral IGFBP5 shRNA was used to silence the IGFBP5. Retroviruses expressing Wild‐type IGFBP5 were used to over‐express IGFBP5. Angiogenic and neurogenic differentiation were carried out by in vitro study. Real‐time RT‐PCR and western blot results showed that over‐expression of IGFBP5 upregulated the expressions of angiogenic markers, including VEGF, PDGFA and ANG‐1, and neurogenic markers, including NCAM, TH, Nestin, βIII‐tubulin, and TH, in DPSCs. Moreover, microscope observation confirmed that over‐expression of IGFBP5 enhanced neurosphere formation in DPSCs in size and amount. Immunofluorescence staining results showed that over‐expression of IGFBP5 also prompted the percentage of Nestin and βIII‐tubulin positive neurospheres in DPSCs. While depletion of IGFBP5 downregulated the expressions of VEGF, PDGFA, ANG‐1, NCAM, TH, Nestin, βIII‐tubulin, and TH, it decreased the neurosphere formation and percentage of Nestin and βIII‐tubulin positive neurospheres in DPSCs. In conclusion, our results revealed that IGFBP5 promoted angiogenic and neurogenic differentiation potential of DPSCs in vitro and provided the possible potential target for enhancing directed differentiation of dental stem cells and dental pulp‐dentin functional regeneration.
Improved bioconversion of lignocellulosic biomass by Saccharomyces cerevisiae engineered for tolerance to acetic acid
Authors: Ko Ja Kyong , Enkh‐Amgalan Tseveendorj , Gong Gyeongtaek , Um Youngsoon , Lee Sun‐Mi 
Published: October 2019

AbstractLignocellulosic biomass has considerable potential for the production of fuels and chemicals as a promising alternative to conventional fossil fuels. However, the bioconversion of lignocellulosic biomass to desired products must be improved to reach economic viability. One of the main technical hurdles is the presence of inhibitors in biomass hydrolysates, which hampers the bioconversion efficiency by biorefinery microbial platforms such as Saccharomyces cerevisiae in terms of both production yields and rates. In particular, acetic acid, a major inhibitor derived from lignocellulosic biomass, severely restrains the performance of engineered xylose‐utilizing S. cerevisiae strains, resulting in decreased cell growth, xylose utilization rate, and product yield. In this study, the robustness of XUSE, one of the best xylose‐utilizing strains, was improved for the efficient conversion of lignocellulosic biomass into bioethanol under the inhibitory condition of acetic acid stress. Through adaptive laboratory evolution, we successfully developed the evolved strain XUSAE57, which efficiently converted xylose to ethanol with high yields of 0.43–0.50 g ethanol/g xylose even under 2–5 g/L of acetic stress. XUSAE57 not only achieved twofold higher ethanol yields but also improved the xylose utilization rate by more than twofold compared to those of XUSE in the presence of 4 g/L of acetic acid. During fermentation of lignocellulosic hydrolysate, XUSAE57 simultaneously converted glucose and xylose with the highest ethanol yield reported to date (0.49 g ethanol/g sugars). This study demonstrates that the bioconversion of lignocellulosic biomass by an engineered strain could be significantly improved through adaptive laboratory evolution for acetate tolerance, which could help realize the development of an economically feasible lignocellulosic biorefinery to produce fuels and chemicals.