bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of T790M Acquisition After Treatment With First- and Second-Generation Tyrosine-Kinase Inhibitors: A Systematic Review and Network Meta-Analysis
Authors: Hsieh Po-Chun , Wu Yao-Kuang , Huang Chun-Yao , Yang Mei-Chen , Kuo Chan-Yen , Tzeng I-Shiang , Lan Chou-Chin 
Published: June 2022

BackgroundLung adenocarcinoma is a common disease with a high mortality rate. Epidermal growth factor receptor (EGFR) mutations are found in adenocarcinomas, and oral EGFR-tyrosine kinase inhibitors (EGFR-TKIs) show good responses. EGFR-TKI therapy eventually results in resistance, with the most common being T790M. T790M is also a biomarker for predicting resistance to first- and second-generation EGFR-TKIs and is sensitive to osimertinib. The prognosis was better for patients with acquired T790M who were treated with osimertinib than for those treated with chemotherapy. Therefore, T790M mutation is important for deciding further treatment and prognosis. Previous studies based on small sample sizes have reported very different T790 mutation rates. We conducted a meta-analysis to evaluate the T790M mutation rate after EGFR-TKI treatment.MethodsWe systematic reviewed the electronic databases to evaluate the T790M mutation rate after treatment with first-generation (gefitinib, erlotinib, and icotinib) and second-generation (afatinib and dacomitinib) EGFR-TKIs. Random-effects network meta-analysis and single-arm meta-analysis were conducted to estimate the T790M mutation rate of the target EGFR-TKIs.ResultsA total of 518 studies were identified, of which 29 were included. Compared with afatinib, a higher odds ratio (OR) of the T790M mutation rate was observed after erlotinib [OR = 1.48; 95% confidence interval (CI):1.09–2.00] and gefitinib (OR = 1.45; 95% CI: 1.11–1.90) treatments. An even OR of the T790M mutation rate was noted after icotinib treatment (OR = 0.91, 95% CI: 0.46–1.79) compared with that after afatinib. The T790M mutation rate was significantly lower with afatinib (33%) than that with gefitinib (49%) and erlotinib treatments (47%) (p &lt; 0.001). The acquired T790M mutation rate in all participants was slightly lower in Asians (43%) than that in Caucasians (47%).ConclusionsErlotinib and gefitinib had a higher OR for the T790M mutation than afatinib. The T790M mutation rate was significantly lower in afatinib than in gefitinib and erlotinib. T790M is of great significance because osimertinib shows a good prognosis in patients with T790M mutation.Systematic Review RegistrationPROSPERO, identifier CRD42021257824.
Subclinical Left Ventricular Dysfunction Detected by Speckle-Tracking Echocardiography in Breast Cancer Patients Treated With Radiation Therapy: A Six-Month Follow-Up Analysis (MEDIRAD EARLY‐HEART study)
Authors: Locquet Médéa , Spoor Daan , Crijns Anne , van der Harst Pim , Eraso Arantxa , Guedea Ferran , Fiuza Manuela , Santos Susana Constantino Rosa , Combs Stephanie , Borm Kai , Mousseaux Elie , Gencer Umit , Frija Guy , Cardis Elisabeth , Langendijk Hans , Jacob Sophie 
Published: June 2022

BackgroundIn the case of breast cancer (BC), radiotherapy (RT) helps reduce locoregional recurrence and BC-related deaths but can lead to cardiotoxicity, resulting in an increased risk of long-term major cardiovascular events. It is therefore of primary importance to early detect subclinical left ventricular (LV) dysfunction in BC patients after RT and to determine the dose–response relationships between cardiac doses and these events.MethodsWithin the frame of the MEDIRAD European project (2017–2022), the prospective multicenter EARLY‐HEART study (ClinicalTrials.gov Identifier: NCT03297346) included chemotherapy naïve BC women aged 40–75 years and treated with lumpectomy and adjuvant RT. Myocardial strain analysis was provided using speckle‐tracking echocardiography performed at baseline and 6 months following RT. A global longitudinal strain (GLS) reduction &gt;15% between baseline and follow-up was defined as a GLS-based subclinical LV dysfunction. Individual patient dose distributions were obtained using multi-atlas-based auto-segmentation of the heart. Dose-volume parameters were studied for the whole heart (WH) and left ventricle (LV).ResultsThe sample included 186 BC women (57.5 ± 7.9 years, 64% left-sided BC). GLS-based subclinical LV dysfunction was observed in 22 patients (14.4%). These patients had significantly higher cardiac exposure regarding WH and LV doses compared to patients without LV dysfunction (for mean WH dose: 2.66 ± 1.75 Gy versus 1.64 ± 0.96 Gy, p = 0.01). A significantly increased risk of subclinical LV dysfunction was observed with the increase in the dose received to the WH [ORs from 1.13 (V5) to 1.74 (Dmean); p &lt;0.01] and to the LV [ORs from 1.10 (V5) to 1.46 (Dmean); p &lt;0.01]. Based on ROC analysis, the LV-V5 parameter may be the best predictor of the short-term onset of subclinical LV dysfunction.ConclusionThese results highlighted that all cardiac doses were strongly associated with the occurrence of subclinical LV dysfunction arising 6 months after BC RT. Whether measurements of GLS at baseline and 6 months after RT combined with cardiac doses can early predict efficiently subclinical events occurring 24 months after RT remains to be investigated.
Radiomic Machine Learning and External Validation Based on 3.0 T mpMRI for Prediction of Intraductal Carcinoma of Prostate With Different Proportion
Authors: Yang Ling , Li Zhengyan , Liang Xu , Xu Jingxu , Cai Yusen , Huang Chencui , Zhang Mengni , Yao Jin , Song Bin 
Published: June 2022

PurposeTo assess the association of radiomics features based on multiparametric MRI (mpMRI) with the proportion of intraductal carcinoma of prostate (IDC-P) and validate the predictive models.Materials and MethodsWe retrospectively included pre-treatment MR images of prostate cancer (PCa) with IDC components of high proportion (≥10%, hpIDC-P), low proportion (&lt;10%, lpIDC-P), and pure acinar adenocarcinoma (PAC) from our institution for training and internal validation and cooperated cohort for external validation. Normalized images of T2WI, diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) map, and dynamic contrast enhanced (DCE) sequences were used for radiomics modeling. The clinical model was built based on serum total prostate specific antigen (tPSA) and Gleason score (GS), and the integrated model was the combination of Rad-score and clinicopathological data. The discrimination ability was assessed by area under the receiver operating characteristic curve (ROC-AUC) in the internal and external validation sets and compared by DeLong test.ResultsOverall, 97 patients with hpIDC-P, 87 lpIDC-P, and 78 PAC were included for training and internal validation, and 11, 16, and 19 patients for external validation. The integrated model for predicting hpIDC-P got the best ROC-AUC of 0.88 (95%CI = 0.83-0.93) in internal and 0.86 (95%CI = 0.72-1.0) in external validation, which both outperformed clinical models (AUC=0.78, 95% CI = 0.72-0.85, AUC=0.69, 95% CI = 0.5-0.85, respectively) based solely on GS, and the radiomics model (AUC=0.85, 95% CI = 0.79-0.91) was slightly inferior to the integrated model and better than the clinical model in internal dataset. The integrated model for predicting lpIDC-P outperformed both radiomics and clinical models in the internal dataset, while slightly inferior to the integrated model for predicting hpIDC-P.ConclusionsRadiomics signature improved differentiation of both hpIDC-P and lpIDC-P versus PAC when compared with the clinical model based on Gleason score, and was validated in an external cohort.
Communicating Risk for Obesity in Early Life: Engaging Parents Using Human-Centered Design Methodologies
Authors: Cheng Erika R. , Moore Courtney , Parks Lisa , Taveras Elsie M. , Wiehe Sarah E. , Carroll Aaron E. 
Published: June 2022

ObjectivePediatricians are well positioned to discuss early life obesity risk, but optimal methods of communication should account for parent preferences. To help inform communication strategies focused on early life obesity prevention, we employed human-centered design methodologies to identify parental perceptions, concerns, beliefs, and communication preferences about early life obesity risk.MethodsWe conducted a series of virtual human-centered design research sessions with 31 parents of infants &lt;24 months old. Parents were recruited with a human intelligence task posted on Amazon's Mechanical Turk, via social media postings on Facebook and Reddit, and from local community organizations. Human-centered design techniques included individual short-answer activities derived from personas and empathy maps as well as group discussion.ResultsParents welcomed a conversation about infant weight and obesity risk, but concerns about health were expressed in relation to the future. Tone, context, and collaboration emerged as important for obesity prevention discussions. Framing the conversation around healthy changes for the entire family to prevent adverse impacts of excess weight may be more effective than focusing on weight loss.ConclusionsOur human-centered design approach provides a model for developing and refining messages and materials aimed at increasing parent/provider communication about early life obesity prevention. Motivating families to engage in obesity prevention may require pediatricians and other health professionals to frame the conversation within the context of other developmental milestones, involve the entire family, and provide practical strategies for behavioral change.
Cost-Effectiveness of Pharmacogenomics-Guided Prescribing to Prevent Gene-Drug-Related Deaths: A Decision-Analytic Model
Authors: van der Wouden Cathelijne H. , Marck Heiralde , Guchelaar Henk-Jan , Swen Jesse J. , van den Hout Wilbert B. 
Published: June 2022

Aim: Prospective studies support the clinical impact of pharmacogenomics (PGx)-guided prescribing to reduce severe and potentially fatal adverse effects. Drug-gene interactions (DGIs) preventing potential drug-related deaths have been categorized as “essential” by the Dutch Pharmacogenetics Working Group (DPWG). The collective clinical impact and cost-effectiveness of this sub-set is yet undetermined. Therefore, we aim to assess impact and cost-effectiveness of “essential” PGx tests for prevention of gene-drug-related deaths, when adopted nation-wide.Methods: We used a decision-analytic model to quantify the number and cost per gene-drug-related death prevented, from a 1-year Dutch healthcare perspective. The modelled intervention is a single gene PGx-test for CYP2C19, DPYD, TPMT or UGT1A1 to guide prescribing based on the DPWG recommendations among patients in the Netherlands initiating interacting drugs (clopidogrel, capecitabine, systemic fluorouracil, azathioprine, mercaptopurine, tioguanine or irinotecan).Results: For 148,128 patients initiating one of seven drugs in a given year, costs for PGx-testing, interpretation, and drugs would increase by €21.4 million. Of these drug initiators, 35,762 (24.1%) would require an alternative dose or drug. PGx-guided prescribing would relatively reduce gene-drug related mortality by 10.6% (range per DGI: 8.1–14.5%) and prevent 419 (0.3% of initiators) deaths a year. Cost-effectiveness is estimated at €51,000 per prevented gene-drug-related death (range per DGI: €-752,000–€633,000).Conclusion: Adoption of PGx-guided prescribing for “essential” DGIs potentially saves the lives of 0.3% of drug initiators, at reasonable costs.
RETRACTED: Abnormal Plasma Levels of Steroids and Their Ratios in Patients With Prurigo Nodularis: A Pilot Study
Authors: Chu Liuxi , Shu Xin , Wu Yan , Yang Haoran , Lu Qin , Deng Huihua 
Published: June 2022

Background: It has been suggested that cortisol levels are abnormal in chronic urticaria and atopic dermatitis, but other steroids, such as dehydroepiandrosterone (DHEA) and testosterone, are still unknown, and whether these hormones affect the maintenance of skin homeostasis or the pathogenesis of skin diseases is not fully understood. Limited data are available on steroid levels in prurigo nodularis (PN)-related research, and no study has examined the association between pruritus severity and steroid levels in PN patients.Aims: This pilot study aimed to investigate the differences in the levels of five steroids combined with their ratios in plasma between PN patients and controls and to examine the associations between the biomarkers and pruritus severity.Methods: Plasma concentrations of five steroids, including cortisol, cortisone, testosterone, progesterone, and dehydroepiandrosterone (DHEA), in 36 patients with PN were compared with concentrations in thirty-six and matched healthy controls. The concentrations of steroids were quantitated using liquid chromatography-tandem mass spectrometry. The PN symptoms, including pruritus severity, pain, and life quality, were assessed with the use of the visual analog scale, prurigo score index, numerical rating scale, and verbal rating scale and dermatology life quality index scores.Results: In comparison with controls, PN patients had lower levels of plasma cortisol and cortisone, which negatively correlated with PN symptoms. PN patients had higher levels of cortisone and testosterone to cortisol, which positively correlated with pruritus severity. Additionally, there were no significant differences in plasma concentrations of DHEA and testosterone between the two groups. We found no correlation between plasma concentrations of DHEA and testosterone and pruritus severity.Conclusion: This pilot study suggests that there may be abnormalities in peripheral blood levels of cortisol, and cortisone and the ratios of cortisone and testosterone to cortisol in patients with PN, and they are related to pruritus severity. The plasma concentrations of testosterone and DHEA may be not abnormal in PN patients and may not be associated with pruritus severity.
Anxiety and Its Influencing Factors in Patients With Drug-Induced Liver Injury
Authors: Liu Yi-Hui , Guo Yan , Xu Hong , Feng Hui , Chen Dong-Ya 
Published: June 2022

ObjectiveThis study aims to investigate anxiety and its influencing factors in patients with drug-induced liver injury (DILI).Materials and MethodsNinety-four patients with DILI were enrolled and evaluated with a self-rating anxiety scale (SAS). According to the anxiety score, they were divided into four groups: the non-anxiety, mild anxiety, moderate anxiety, or severe anxiety groups, and the scores were analyzed based on demographic and biochemical indicators.ResultsOf the 94 patients with DILI, 63 did not have anxiety and 31 had anxiety (32.9%), of which 27 had mild, 3 had moderate, and 1 had severe anxiety. There were no statistically significant differences in gender, age, occupation, and level of education between the groups (F= 1.42,H= 2.361,H= 6.751,H= 1.796, andP&gt; 0.05); anxiety score and degree of anxiety between the types of drugs that led to the liver injury (H= 0.812,H= 1.712, andP&gt; 0.05); anxiety score between the different degrees of liver injury (H= 2.836,H= 4.957,P&gt; 0.05); or length of hospital stay or prognosis between the degrees of anxiety (F= 1.487,H= 0.761,P&gt; 0.05). However, there were statistically significant differences in the degree of anxiety between different degree and types of liver injury (H= 7.981,H= 8.208,P&lt; 0.05).ConclusionPatients with DILI may have anxiety, especially mild anxiety. The occurrence of anxiety in patients with DILI is not related to gender, age, occupation, or level of education but may be related to the degree and type of liver injury. Anxiety has no impact on the length of stay in hospital or the prognosis of the DILI. These findings may contribute to the development of management strategies for patients with DILI.
Crocetin Protected Human Hepatocyte LO2 Cell From TGF-β-Induced Oxygen Stress and Apoptosis but Promoted Proliferation and Autophagy via AMPK/m-TOR Pathway
Authors: Guo Hongxing , Ruan Chenyu , Zhan Xiuhong , Pan Hao , Luo Yumei , Gao Ke 
Published: June 2022

ObjectiveTo investigate the protective effects of crocetin against transforming growth factor-β (TGF-β)—induced injury in LO2 cells.MethodsHuman hepatocyte LO2 cells were pre-treated with crocetin (10 μM) for 6, 12, and 24 h, and then induced by TGF-β. Proliferation, oxidative stress, apoptosis, autophagy, and related proteins were assessed.ResultsCrocetin pre-treating promoted proliferation but suppressed apoptosis in TGF-β-induced LO2 cells. Crocetin protected LO2 cells from TGF-β-induced inflammation and oxygen stress by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) but enhancing superoxide dismutase (SOD) and glutathione (GSH). Autophagy was suppressed in TGF-β but crocetin promoted autophagy in LO2 cells by mediating Adenosine 5'-monophosphate—activated protein kinase (AMPK)/mammalian target of rapamycin (m-TOR) signaling pathway via upregulating p-AMPK and p-Beclin-1 but downregulating p-mTOR.ConclusionsCrocetin protected LO2 cells from TGF-β-induced damage by promoting proliferation and autophagy, and suppressing apoptosis and anti-inflammation via regulation of AMPK/m-TOR signaling pathway.
Analysis of the Dose-Response Relationship Between the International Normalized Ratio and Hepatic Encephalopathy in Patients With Liver Cirrhosis Using Restricted Cubic Spline Functions
Authors: Tan Juntao , He Yuxin , Li Zhanbiao , Zhang Qinghua , Yang Yanzhi , Xu Qian , Xu Xiaomei 
Published: June 2022

BackgroundThe International Normalized Ratio (INR) is significantly associated with Hepatic Encephalopathy (HE) in patients with liver cirrhosis. However, the dose-response relationship between continuous INR changes and HE risk has not been clearly defined. Thus, our goal was to explore the continuous relationship between HE and INR among patients hospitalized with liver cirrhosis and to evaluate the role of the INR as a risk factor for HE in these patients.MethodsA total of 6,266 people were extracted from the Big Data Platform of the Medical Data Research Institute of Chongqing Medical University. In this study, unconditional logistic regression and restricted cubic spline (RCS) model were used to analyze the dose-response association of INR with HE. Alcoholic liver disease, smoking status, and drinking status were classified for subgroup analysis.ResultsThe prevalence of HE in the study population was 8.36%. The median INR was 1.4. After adjusting for alcoholic liver disease, age, smoking status, drinking status, total bilirubin, neutrophil percentage, total hemoglobin, aspartate aminotransferase, serum sodium, albumin, lymphocyte percentage, serum creatinine, red blood cell, and white blood cell, multivariate logistic regression analysis revealed that INR ≥ 1.5 (OR = 2.606, 95% CI: 2.072–3.278) was significantly related to HE risk. The RCS model showed a non-linear relationship between the INR and HE (non-linear test, χ2 = 30.940, P &lt; 0.001), and an increased INR was an independent and adjusted dose-dependent risk factor for HE among patients with liver cirrhosis.ConclusionThis finding could guide clinicians to develop individualized counseling programs and treatments for patients with HE based on the INR risk stratification.
Toward Exempting from Sentinel Lymph Node Biopsy in T1 Breast Cancer Patients: A Retrospective Study
Authors: Li Guozheng , Zhao Jiyun , Zhang Xingda , Ma Xin , Li Hui , Chen Yihai , Zhang Lei , Zhang Xin , Wu Jiale , Wang Xinheng , Zhang Yan , Xu Shouping 
Published: June 2022

Background and ObjectiveSentinel lymph node biopsy (SLNB) is used to assess the status of axillary lymph node (ALN), but it causes many adverse reactions. Considering the low rate of sentinel lymph node (SLN) metastasis in T1 breast cancer, this study aims to identify the characteristics of T1 breast cancer without SLN metastasis and to select T1 breast cancer patients who avoid SLNB through constructing a nomogram.MethodsA total of 1,619 T1 breast cancer patients with SLNB in our hospital were enrolled in this study. Through univariate and multivariate logistic regression analysis, we analyzed the tumor anatomical and clinicopathological factors and constructed the Heilongjiang Medical University (HMU) nomogram. We selected the patients exempt from SLNB by using the nomogram.ResultsIn the training cohort of 1,000 cases, the SLN metastasis rate was 23.8%. Tumor volume, swollen axillary lymph nodes, pathological types, and molecular subtypes were found to be independent predictors for SLN metastasis in multivariate regression analysis. Distance from nipple or surface and position of tumor have no effect on SLN metastasis. A regression model based on the results of the multivariate analysis was developed to predict the risk of SLN metastasis, indicating an AUC of 0.798. It showed excellent diagnostic performance (AUC = 0.773) in the validation cohort.ConclusionThe HMU nomogram for predicting SLN metastasis incorporates four variables, including tumor volume, swollen axillary lymph nodes, pathological types, and molecular subtypes. The SLN metastasis rates of intraductal carcinoma and HER2 enriched are 2.05% and 6.67%. These patients could be included in trials investigating the SLNB exemption.
SOX30 Overexpression Reflects Tumor Invasive Degree, Lymph Node Metastasis and Predicts Better Survival in Colorectal Cancer Patients: A Long-Term Follow-Up Cohort Study
Authors: Li Chao , Li Pengfei , Yu Lulu , Sun Qingsen , Gu Bin , Sun Yanhua , Sun Liansheng 
Published: June 2022

AimsSex-determining region Y-box containing gene 30 (SOX30) takes part in the progression of several cancers, while its clinical engagement in colorectal cancer (CRC) is obscure. Therefore, this study aimed to explore the association of SOX30 with clinicopathological features and prognosis in CRC patients.MethodsTumor and adjacent noncancerous specimens of 195 CRC patients who received resection were acquired. Furthermore, an immunohistochemistry assay was performed to detect SOX30 protein expression in these specimens; meanwhile, SOX30 mRNA expression was determined by reverse transcription-quantitative polymerase chain reaction assay in 95 out of 195 specimens. Moreover, clinical characteristics and survival data (follow-up duration median (range): 71.0 (7.0-95.0) months) of CRC patients were gathered.ResultsSOX30 protein and mRNA expressions were both decreased in CRC tumor tissue compared to adjacent tissue (both P &lt; 0.001). Furthermore, a negative correlation was found in tumor SOX30 protein expression with tumor size (P = 0.049), lymph node (LYN) metastasis (P = 0.018), T stage (P = 0.001), N stage (P = 0.034), and TNM stage (P = 0.001); tumor SOX30 mRNA expression was also negatively correlated with LYN metastasis (P = 0.001), T stage (P = 0.019), N stage (P = 0.004), and TNM stage (P &lt; 0.001). Furthermore, tumor SOX30 protein expression was positively correlated with overall survival (OS) (P = 0.017), while tumor SOX30 mRNA expression was not correlated with OS (P = 0.070). Multivariate Cox’s regression analysis illustrated that tumor SOX30 protein high expression was an independent factor for favorable OS (hazard ratio: 0.525, P = 0.034).ConclusionsSOX30 has potential as a biomarker for the progression and prognostication of CRC, which might improve the management of CRC.