bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth
Authors: Qu Yuan-Yuan , Zhao Rui , Zhang Hai-Liang , Zhou Qian , Xu Fu-Jiang , Zhang Xuan , Xu Wen-Hao , Shao Ning , Zhou Shu-Xian , Dai Bo , Zhu Yao , Shi Guo-Hai , Shen Yi-Jun , Zhu Yi-Ping , Han Cheng-Tao , Chang Kun , Lin Yan , Zang Wei-Dong , Xu Wei , Ye Ding-Wei , Zhao Shi-Min , Zhao Jian-Yuan 
Published: November 2019

Abstract

The tumorigenic role and underlying mechanisms of lipid accumulation, commonly observed in many cancers, remain insufficiently understood. In this study, we identified an AMP-activated protein kinase (AMPK)–GATA-binding protein 3 (GATA3)–enoyl-CoA hydratase short-chain 1 (ECHS1) pathway that induces lipid accumulation and promotes cell proliferation in clear cell renal cell carcinoma (ccRCC). Decreased expression of ECHS1, which is responsible for inactivation of fatty acid (FA) oxidation and activation of de novo FA synthesis, positively associated with ccRCC progression and predicted poor patient survival. Mechanistically, ECHS1 downregulation induced FA and branched-chain amino acid (BCAA) accumulation, which inhibited AMPK-promoted expression of GATA3, a transcriptional activator of ECHS1. BCAA accumulation induced activation of mTORC1 and de novo FA synthesis, and promoted cell proliferation. Furthermore, GATA3 expression phenocopied ECHS1 in predicting ccRCC progression and patient survival. The AMPK–GATA3–ECHS1 pathway may offer new therapeutic approaches and prognostic assessment for ccRCC in the clinic.

Significance:
These findings uncover molecular mechanisms underlying lipid accumulation in ccRCC, suggesting the AMPK–GATA3–ECHS1 pathway as a potential therapeutic target and prognostic biomarker.
CDK4/6 Inhibitor Biomarker Research: Are We Barking Up the Wrong Tree?
Authors: Anurag Meenakshi , Haricharan Svasti , Ellis Matthew J. 
Published: November 2019

Abstract
CDK4/6 inhibitors have emerged as a significant advance for the treatment of patients with advanced estrogen receptor–positive breast cancer. However, the identification of predictive markers that optimize their use is proving harder than expected. In this commentary we advocate for unbiased discovery and a collaborative approach across trials.
See related article by Finn et al., p. 110
Boundary Layer Quasi-Equilibrium Limits Convective Intensity Enhancement from the Diurnal Cycle in Surface Heating
Authors: Hansen Zachary R. , Back Larissa E. , Zhou Peigen 
Published: November 2019

AbstractA combination of cloud-permitting model (CPM) simulations, satellite, and reanalysis data are used to test whether the diurnal cycle in surface temperature has a significant impact on the intensity of deep convection as measured by high-percentile updraft velocities, lightning, and CAPE. The land–ocean contrast in lightning activity shows that convective intensity varies between land and ocean independently from convective quantity. Thus, a mechanism that explains the land–ocean contrast must be able to do so even after controlling for precipitation variations. Motivated by the land–ocean contrast, we use idealized CPM simulations to test the impact of the diurnal cycle on high-percentile updrafts. In simulations, updrafts are somewhat enhanced due to large-scale precipitation enhancement by the diurnal cycle. To control for large-scale precipitation, we use statistical sampling techniques. After controlling for precipitation enhancement, the diurnal cycle does not affect convective intensities. To explain why sampled updrafts are not enhanced, we note that CAPE is also not increased, likely due to boundary layer quasi equilibrium (BLQE) occurring over our land area. Analysis of BLQE in terms of net positive and negative mass flux finds that boundary layer entrainment, and even more importantly downdrafts, account for most of the moist static energy (MSE) sink that is balancing surface fluxes. Using ERA-Interim data, we also find qualitative evidence for BLQE over land in the real world, as high percentiles of CAPE are not greater over land than over ocean.
Comparison between magnetic resonance hysterosalpingography and conventional hysterosalpingography: direct visualization of the fallopian tubes using a novel MRI contrast agent mixture
Authors: Duan Na , Chen Xiao , Yin Yanyun , Wang Zhongqiu , Chen Rong 
Published: November 2019

Background Magnetic resonance hysterosalpingography (MR-HSG) is a promising technique in the work-up of female infertility. Few existing MR-HSG studies focus on the comparison between MR-HSG with gold standard examination. Purpose To compare the diagnostic value of MR-HSG with conventional HSG in patients receiving both exams in one day. Material and Methods This study included 33 infertile women who completed pelvic MR scanning, HSG, and MR-HSG in that order. A traditional HSG contrast agent (iohexol) and a magnetic resonance imaging (MRI) contrast agent (1 mL gadopentetate dimeglumine (Gd-DTPA) blended with 100 mL iohexol) were used to achieve image enhancement. Inter-observer and inter-modality agreements of HSG and MR-HSG exams were assessed. The results were calculated by using the kappa test. Three radiologists who were blinded to the clinical data independently reviewed the MR images. Extratubal abnormalities were analyzed. Results A total of 62 fallopian tubes of 33 women were included in the study. MR-HSG imaging findings to depict tubal patency were similar to these of HSG (AUC 0.911, sensitivity 0.821, specificity 1.000, positive predictive values 1.000, and negative predictive values 0.872). Pairwise inter-observer agreement among three observers and inter-modality agreement of the diagnosis were excellent (mean kappa 0.863 and 0.835, respectively). In addition, 29 extratubal abnormalities in 21 patients were found on pelvic MR scanning. Conclusion MR-HSG and HSG demonstrated similar results in assessing tubal patency. Because it offers the comprehensive assessment of female pelvic structures, and avoids ionizing radiation, MR-HSG may be used as an alternative imaging technique for evaluation of female infertility.
Diagnostic Performance of Magnetic Resonance Imaging for Detecting Meniscal Ramp Lesions in Patients With Anterior Cruciate Ligament Tears: A Systematic Review and Meta-analysis
Authors: Koo Boyeon , Lee Sun Hwa , Yun Seong Jong , Song Jae Gwang 
Published: November 2019

Background: The clinical importance of meniscal ramp lesions in patients with anterior cruciate ligament (ACL) tear has emerged as a major issue. However, the diagnostic accuracy of magnetic resonance imaging (MRI) for detecting ramp lesions has a wide range. Purpose: To perform a systematic review and meta-analysis of the diagnostic performance of MRI for diagnosing ramp lesion in patients with ACL tear. Study Design: Systematic review and meta-analysis. Methods: A literature search of PubMed, EMBASE, and the Cochrane Library was performed based on the revised guidelines for the PRISMA DTA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Accuracy Studies) statement. Diagnostic performance studies using MRI as the index test and arthroscopy as the reference standard for ramp lesion were included. Bivariate and hierarchical summary receiver operating characteristic modeling was used to evaluate the diagnostic performance. Meta-regression analyses were performed to identify potential sources of heterogeneity. Results: The review and meta-analysis included 9 studies from 8 articles (883 patients with ACL tear and reconstruction). The summary sensitivity, summary specificity, and area under the hierarchical summary receiver operating characteristic for ramp lesion were 0.71 (95% CI, 0.59-0.81), 0.94 (95% CI, 0.88-0.97), and 0.90 (95% CI, 0.87-0.92), respectively. Among the potential covariates, magnet strength ( P < .01), patient knee position ( P = .04), and MRI interpreter ( P = .04) were associated with heterogeneity in terms of sensitivity, whereas magnet strength ( P = .03) was associated with heterogeneity in terms of specificity. Conclusion: MRI demonstrated moderate sensitivity and excellent specificity for diagnosing ramp lesion. Routine arthroscopic assessment is recommended for the presence of ramp lesion, regardless of whether it is suspected on MRI. Further clinicoradiological studies of diagnostic algorithms are needed for identifying ramp lesion, including high-resolution MRI with appropriate knee position.
Emergency department telemedicine consults decrease time to interpret computed tomography of the head in a multi-network cohort
Authors: Swanson Morgan B , Miller Aspen C , Ward Marcia M , Ullrich Fred , Merchant Kimberly AS , Mohr Nicholas M 
Published: November 2019

Introduction Telemedicine can improve access to emergency stroke care in rural areas, but the benefit of telemedicine across different types and models of telemedicine networks is unknown. The objectives of this study were to (a) identify the impact of telemedicine on emergency department (ED) stroke care, (b) identify if telemedicine impact varied by network and (c) describe the variation in process outcomes by telemedicine across EDs. Methods A prospective cohort study identified stroke patients in four telemedicine networks between November 2015 and December 2017. Primary exposure was telemedicine consultation during ED evaluation. Outcomes included: (a) interpretation of computed tomography (CT) of the head within 45 minutes and (b) time to administer tissue plasminogen activator (tPA). An interaction term tested for differences in telemedicine effect on stroke care by network and hospital. Results Of the 932 stroke subjects, 36% received telemedicine consults. For subjects with a last known well time within two hours of ED arrival (27.9%), recommended CT interpretation within 45 minutes was met for 66.8%. Telemedicine was associated with higher odds of timely head CT interpretation (adjusted odds ratio = 3.03; 95% confidence interval (CI) 1.69–5.46). The magnitude of the association between telemedicine and time to interpret a CT of the head differed between telemedicine networks (interaction term p = 0.033). Among eligible patients, telemedicine was associated with faster time to administer tPA (adjusted hazard ratio = 1.81; 95% CI 1.31–2.50). Discussion Telemedicine consultation during the ED encounter decreased the time to interpret at CT of the head among stroke patients, with differing magnitudes of benefit across telemedicine networks. The effect of heterogeneity of telestroke affects across different networks should be explored in future analyses.
Immune checkpoint inhibitor-associated gastrointestinal and hepatic adverse events and their management
Authors: Shivaji Uday N. , Jeffery Louisa , Gui Xianyong , Smith Samuel C. L. , Ahmad Omer F. , Akbar Ayesha , Ghosh Subrata , Iacucci Marietta 
Published: November 2019

Background: Drug-induced colitis is a known complication of therapies that alter the immune balance, damage the intestinal barrier or disturb intestinal microbiota. Immune checkpoint inhibitors (ICI) directed against cancer cells may result in activated T lymphocyte-induced immune-related adverse events (AEs), including immune-related colitis and hepatitis. The aim of this review article is to summarize the incidence of gastrointestinal (GI) and hepatic AEs related to ICI therapy. We have also looked at the pathogenesis of immune-mediated AEs and propose management strategies based on current available evidence. Methods: A literature search using PubMed and Medline databases was undertaken using relevant search terms pertaining to names of individual drugs, mechanism of action, related AEs and their management. Results: ICI-related GI AEs are common, and colitis appears to be the most common side effect, with some studies reporting incidence as high as 30%. The incidence of both all-grade colitis and hepatitis were highest with combination therapy with anti-CTLA-4/PD-1; severity of colitis was dose-dependent (anti-CTLA-4). Early intervention is associated with better outcomes. Conclusion: ICI-related GI and hepatic AEs are common and clinicians need to be aware. Patients with GI AEs benefit from early diagnosis using endoscopy and computed tomography. Early intervention with oral steroids is effective in the majority of patients, and in steroid-refractory colitis infliximab and vedolizumab have been reported to be useful; mycophenolate has been used for steroid-refractory hepatitis.
Body mass index in women aged 18 to 45 and subsequent risk of heart failure
Authors: Björck Lena , Lundberg Christina , Schaufelberger Maria , Lissner Lauren , Adiels Martin , Rosengren Annika 
Published: November 2019

Background The incidence of heart failure (HF) is decreasing in older ages, but increasing rates have been observed among younger persons in Sweden. Therefore, we investigated the relationship between risk of hospitalization for HF and body mass index (BMI). Methods This was a prospective registry-based cohort study. We included 1,374,031 women aged 18–45 years (mean age 27.9 years) who gave birth during 1982–2014, and were registered in the Medical Birth Register. Information on hospitalization because of HF was collected through linkage to the National Inpatient Register. Results Compared to women with a BMI of 20–<22.5 kg/m2, women with a BMI of 22.5–<25.0 had a hazard ratio (HR) of 1.24 (95% confidence interval (CI), 1.10–1.39) for HF after adjustment for age, year, parity, baseline disorders, smoking, and education. The HR (95% CI) increased to 1.56 (1.36–1.78), 2.39 (2.05–2.78), 2.82 (2.43–3.28), and 4.51 (3.63–5.61) in women with a BMI of 25–<27.5, 27.5–<30, 30–<35, and ≥35 kg/m2, respectively. The multiple-adjusted HRs (95% CI) associated with risk of HF per one-unit increase in BMI in women with a BMI ≥ 22.5 kg/m2 ranged from 1.01 (0.97–1.06) for HF related to valvular disease to 1.14 (1.12–1.15) for coronary heart disease, diabetes, or hypertension. Conclusion Increasing body weight was strongly associated with the risk of early HF in women. Compared with lean women, the risk for HF started to increase at high-normal BMI levels, and was nearly five-fold in women with a BMI ≥ 35 kg/m2.
A modified proximally based nail bed flap approach for benign subungual bone tumors in the distal phalanx
Authors: Hong Seok Woo , Kim Jihyeung , Jang Seonpyo , Lee Min Ho , Gong Hyun Sik , Baek Goo Hyun 
Published: November 2019

Background: Complete tumor removal and damaged nail bed repair are critical factors that determine the success of subungual tumor excision. We examined a modified proximally based nail bed flap approach for excision of subungual bone tumors of the distal phalanx and present cases where this approach was used, along with postoperative functional and cosmetic outcomes. Methods: Twenty-four benign subungual bone tumors, identified from 23 patients (9 males and 14 females), were included in this study. All patients underwent tumor excision by the modified proximally based nail bed flap approach. Pain was assessed using a numeric rating scale, and cosmesis was self-assessed using a visual analog scale preoperatively and 1 year postoperatively. We measured sensation of the involved digit tip, relative to opposite-side sensation, using static and moving two-point discrimination and Semmes–Weinstein monofilament tests 1 year postoperatively. Lastly, we assessed postoperative nail deformities and tumor recurrence as potential surgical complications. Results: Mean pain severity and cosmesis were significantly improved 1 year postoperatively. There were no significant differences in the digit tip sensation between the involved and the opposite-side digits 1 year postoperatively. We observed one case of tumor recurrence and four cases of postoperative nail deformities. Conclusions: The modified proximally based nail bed flap approach showed satisfactory functional and cosmetic outcomes. This approach enables a low rate of recurrence after removal of benign subungual bone tumors in the short term and cosmetically superior nail bed repair. Level of evidence: Therapeutic, IV
MoMI-G: modular multi-scale integrated genome graph browser
Authors: Yokoyama Toshiyuki T. , Sakamoto Yoshitaka , Seki Masahide , Suzuki Yutaka , Kasahara Masahiro 
Published: November 2019

AbstractBackgroundGenome graph is an emerging approach for representing structural variants on genomes with branches. For example, representing structural variants of cancer genomes as a genome graph is more natural than representing such genomes as differences from the linear reference genome. While more and more structural variants are being identified by long-read sequencing, many of them are difficult to visualize using existing structural variants visualization tools. To this end, visualization method for large genome graphs such as human cancer genome graphs is demanded.ResultsWe developed MOdular Multi-scale Integrated Genome graph browser, MoMI-G, a web-based genome graph browser that can visualize genome graphs with structural variants and supporting evidences such as read alignments, read depth, and annotations. This browser allows more intuitive recognition of large, nested, and potentially more complex structural variations. MoMI-G has view modules for different scales, which allow users to view the whole genome down to nucleotide-level alignments of long reads. Alignments spanning reference alleles and those spanning alternative alleles are shown in the same view. Users can customize the view, if they are not satisfied with the preset views. In addition, MoMI-G has Interval Card Deck, a feature for rapid manual inspection of hundreds of structural variants. Herein, we describe the utility of MoMI-G by using representative examples of large and nested structural variations found in two cell lines, LC-2/ad and CHM1.ConclusionsUsers can inspect complex and large structural variations found by long-read analysis in large genomes such as human genomes more smoothly and more intuitively. In addition, users can easily filter out false positives by manually inspecting hundreds of identified structural variants with supporting long-read alignments and annotations in a short time.Software availabilityMoMI-G is freely available athttps://github.com/MoMI-G/MoMI-Gunder the MIT license.
The midline approach for endotracheal intubation using GlideScope video laryngoscopy could provide better glottis exposure in adults: a randomized controlled trial
Authors: Jiang Lianxiang , Qiu Shulin , Zhang Peng , Yao Weidong , Chang Yan , Dai Zeping 
Published: November 2019

Abstract

Background
Previous studies have demonstrated that the common laryngoscopic approach (right-sided) and midline approach are both used for endotracheal intubation by direct laryngoscopy. Although the midline approach is commonly recommended for video laryngoscopy (VL) in the clinic, there is a lack of published evidences to support this practice. This study aimed to evaluate the effects of different video laryngoscopic approaches on intubation.

Methods
Two hundred sixty-two patients aged 18 years who underwent elective surgery under general anaesthesia and required endotracheal intubation were included in the present prospective, randomized, controlled study. The participants were randomly and equally allocated to the right approach (Group R) or midline approach (Group M). All the intubations were conducted by experienced anaesthetists using GlideScope video laryngoscopy. The primary outcomes were Cormack-Lehane laryngoscopic views (CLVs) and first-pass success (FPS) rates. The secondary outcomes were the time to glottis exposure, time to tracheal intubation, haemodynamic responses and other adverse events. Comparative analysis was performed between the groups.

Results
Finally, 262 patients completed the study, and all the tracheas were successfully intubated. No significant differences were observed in the patient characteristics and airway assessments (P > 0.05). Compared with Group R, Group M had a better CLV (χ2 = 14.706, P = 0.001) and shorter times to glottis exposure (8.82 ± 2.04 vs 12.38 ± 1.81; t = 14.94; P < 0.001) and tracheal intubation (37.19 ± 5.01 vs 45.23 ± 4.81; t = 13.25; P < 0.001), but no difference was found in the FPS rate (70.2% vs 71.8%; χ2 = 0.074; P = 0.446) and intubation procedure time (29.86 ± 2.56 vs 30.46 ± 2.97, t = 1.75, P = 0.081). Between the groups, the rates of hoarseness or sore throat, minor injury, hypoxemia and changes in SBP and HR showed no significant difference (P > 0.05).

Conclusion
Although the FPS rate did not differ based on the laryngoscopic approach, the midline approach could provide better glottis exposure and shorter times to glottis exposure and intubation. The midline approach should be recommended for teaching in VL-assisted endotracheal intubation.

Trial registration
The study was registered on May 18, 2019 in the Chinese Clinical Trial Registry (ChiCTR1900023252).
European Medicines Agency Policy 0070: an exploratory review of data utility in clinical study reports for academic research
Authors: Ferran Jean-Marc , Nevitt Sarah J. 
Published: November 2019

Abstract

Background
Clinical study reports (CSRs) have been increasingly utilised within academic research in recent years. European Medicines Agency (EMA) Policy 0070 ‘Phase 1,’ which came into effect in January 2015, requires the publication of regulatory documents such as CSRs from central applications in an anonymised format. EMA Policy 0070 requires sponsors to demonstrate careful consideration of data utility within anonymised CSRs published within the scope of the policy, yet the concept of data utility is not clearly defined in the associated anonymisation guidance.

Objective
To review the use of data from CSRs in published academic research and to hypothesise the potential data utility of CSRs anonymised under the objectives of EMA Policy 0070 for future academic research.

Methods
Review of the objectives, research methodologies and findings of academic research reports using unpublished data from CSRs (prior to EMA Policy 0070). Semi-structured interviews with authors of academic research reports, including questions related to data utility of anonymised CSRs published under EMA Policy 0070.

Results
Thirteen academic research reports were identified and reviewed. The research purposes ranged from assessment of reporting bias, comparison of methods and results with published data sources, detailed evaluation of harms and adverse events, re-analysis and novel analyses including systematic reviews and meta-analysis. All of the examples identified required access to the methods and results sections of CSRs (including aggregated summary tables) and research purposes relating to evaluation of adverse events also required access to participant narratives. Retaining anonymised participant narratives relating to interventions, findings and events, while maintaining an acceptably low risk of participant re-identification, may provide an important gain in data utility and further understanding of drug safety profiles.

Conclusions
This work provides an initial insight into the previous use of CSR data and current practices for including regulatory data in academic research. This work also provides early guidance to qualitatively assess and document data utility within anonymised CSRs published under EMA Policy 0070.