bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction and validation of a nomogram to predict overall survival in patients with breast sarcoma
Authors: Cheng Yixin , Zhang Pengkun , Huang Yulin , Tang Ru , Zhang Lei , Sun Jiayuan , Chi Feng , Wu San-Gang , He Zhenyu 
Published: October 2022

BackgroundThis study aimed to construct a nomogram for Breast sarcoma (BS) to predict the prognosis of patients with BS accurately and provide a theoretical basis for individualized treatment.MethodsPatients selected from the Surveillance, Epidemiology and End Results (SEER) database from 2000 to 2018 were assigned to a training group (TG, n = 696) and an internal validation group (IVG, n = 299) at a 7:3 ratio. Cox regression analysis was performed on the TG, and statistically significant factors were used to establish a nomogram to predict 3-, 5-, and 10-year overall survival (OS). The nomogram’s predictive power was validated using data from patients who attended our institution as the external validation group (EVG, n =79).ResultsCox regression analysis identified five factors, which were used to construct the nomogram. Good prediction accuracy was demonstrated using calibration curves. The concordance (C) indices for TG = 0.804 (95% confidence interval (CI) 0.777–0.831) and IVG = 0.761 (0.716–0.806) were higher than those based on 8th American Joint Committee on Cancer (AJCC8) stage: TG = 0.695 (0.660–0.730), IVG = 0.637 (0.584–0.690). The EVG also had a high C-index: 0.844 (0.768–0.920). Decision curve analysis showed that nomogram has larger net benefits than the AJCC8. The Kaplan–Meier curves of the nomogram-based risk groups showed significant differences (p &lt; 0.001).ConclusionsThe nomogram could accurately predict 3-, 5-, and 10-year OS and provided nomogram-based risk stratification, which could help physicians to personalize treatment plans for patients with BS.
Feasibility and Efficacy of Adjuvant Chemotherapy With Gemcitabine After Liver Transplantation for Perihilar Cholangiocarcinoma - A Multi-Center, Randomized, Controlled Trial (pro-duct001)
Authors: Schmelzle Moritz , Benzing Christian , Fischer Lutz , Herden Uta , Sterneck Martina , Settmacher Utz , Bauschke Astrid , Neumann Ulf , Pelzer Uwe , Müller Tobias , Strassburg Christian , Lang Hauke , Becker Thomas , Königsrainer Alfred , Nadalin Silvio , Quante Markus , Paul Andreas , Friess Helmut , Klempnauer Jürgen , Richter Nicolas , Vondran Florian , Pascher Andreas , Rösch Thomas , Schöning Wenzel , Krenzien Felix , Öllinger Robert , Seehofer Daniel , Neuhaus Peter , Pratschke Johann 
Published: October 2022

BackgroundLiver transplantation (LT) is considered a therapeutic option for unresectable perihilar cholangiocarcinoma (PHC) within defined criteria. It remains uncertain whether patients can safely receive adjuvant chemotherapy after LT.MethodsWe performed a prospective, multi-center, randomized, non-blinded two-arm trial (pro-duct001). Patients after LT for unresectable PHC within defined criteria were randomized to adjuvant gemcitabine (LT-Gem group) and LT alone (LT alone group). The primary objective was to investigate if adjuvant chemotherapy is feasible in ≥ 85% of patients after LT. The primary endpoint was the percentage of patients completing the 24 weeks course of adjuvant chemotherapy. Secondary endpoints included overall survival (OS) and disease-free (DFS), and complication rates.ResultsTwelve patients underwent LT for PHC, of which six (50%) were eligible for randomization (LT-Gem: three patients, LT alone: three patients). Two out of three patients discontinued adjuvant chemotherapy after LT due to intolerance. The study was prematurely terminated due to slow enrollment. One patient with PHC had underlying primary sclerosing cholangitis (PSC). Tumor-free margins could be achieved in all patients. In both the LT-Gem and the LT alone group, the cumulative 1-, 3-, and 5-year OS and DFS rates were 100%, 100%, 67%, and 100%, 67% and 67%, respectively.ConclusionsThis prospective, multi-center study was prematurely terminated due to slow enrollment and a statement on the defined endpoints cannot be made. Nevertheless, long-term survival data are consistent with available retrospective data and confirm defined criteria for LT. Since more evidence of LT per se in unresectable PHC is urgently needed, a prospective, non-randomized follow-up study (pro-duct002) has since been launched.
Ultrasound-guided posterior quadratus lumborum block can reduce postoperative opioid consumption and promote rapid recovery in patients undergoing sutureless laparoscopic partial nephrectomy: A triple-blind, randomized, controlled study
Authors: Zhu Youzhuang , Li Zhichao , Qin Shangyuan , Xu Hao , He Jianshuai , Sheng Fang , Zhao Qin , Kang Yihan , Gao Xin , Li Si , Chai Jun , Chen Lina , Wang Weiwei 
Published: October 2022

PurposeWe hypothesized that posterior quadratus lumborum block would reduce postoperative opioid consumption and improve the quality of recovery in patients undergoing sutureless laparoscopic partial nephrectomy.Materials and methodsThe study included 60 patients, ages 18−65 with American Society of Anesthesiologists scores of I-II scheduled for elective sutureless laparoscopic partial nephrectomy. Before general anesthesia, 60 participating patients were randomly allocated to receive a 30-ml injection posterior to the quadratus lumborum muscle with either 0.375% ropivacaine (n = 30) or normal saline (n = 30). The primary outcomes included cumulative opioid consumption within 12 h postoperatively and quality of postoperative recovery at 48 h. Secondary outcomes included the Numerical Rating Scale (NRS), opioid consumption by period, first time to press the analgesic pump, number of patients needing rescue analgesia, blood glucose and cortisol concentrations, early postoperative recovery indicators, and adverse events.ResultsThere were 48 patients included in the final analysis. The intervention group had lower cumulative consumption of sufentanil within 12 h postoperatively and higher quality of postoperative recovery scores at 48 h postoperatively compared with the control group (p &lt; 0.001). The NRS at resting and movement of the intervention group was lower at 0 h, 6 h, and 12 h after surgery than in the control group (p &lt; 0.05). At prespecified intervals (0 to 2 h, 2 to 6 h, 6 to 12 h, 12 to 24 h, and 24 to 48 h) after surgery, the intervention group had lower consumption of sufentanil compared with the control group (p &lt; 0.05). The intervention group took longer to press the analgesic pump for the first time within 48 h after surgery compared with the control group (p &lt; 0.001). The postoperative blood glucose and cortisol concentrations in the intervention group were lower than in the control group (p &lt; 0.05). The times to first excretion, ambulation, and discharge were shorter in the intervention group compared with the control group (p &lt; 0.05). There was no significant difference in adverse events between the two groups.ConclusionsOur trial demonstrated that patients who received posterior quadratus lumborum block had significantly lower opioid consumption within 12 h postoperatively and had a better quality of recovery at 48 h postoperatively. Therefore, we recommend posterior quadratus lumborum block as an option for postoperative analgesia in patients undergoing sutureless laparoscopic partial nephrectomy.Trial Registrationhttp://www.chictr.org.cn, identifier ChiCTR2100053439.
A performance review of novel adiposity indices for assessing insulin resistance in a pediatric Latino population
Authors: McGraw Mac B. , Kohler Lindsay N. , Shaibi Gabriel Q. , Mandarino Lawrence J. , Coletta Dawn K. 
Published: October 2022

IntroductionBody mass index (BMI) percentile or BMI adjusted for age and sex is the most common anthropometric index to monitor and assess obesity in children. However, the ability of BMI to accurately predict insulin resistance (IR) in youth is debated. Determining the best method to noninvasively measure IR in the pediatric population is especially important due to the growing prevalence of type 2 diabetes mellitus (T2DM), which is more likely to develop in people with IR. Therefore, this study analyzed the performance of BMI against newer anthropometric indices in assessing IR in a pediatric Latino identifying sample.MethodsWe studied 127 pediatric Latino participants from the Arizona Insulin Resistance (AIR) registry and performed linear regression analyses between various measures of IR and adiposity indices, including body mass index (BMI), triponderal mass index (TMI), body adiposity index (BAI), pediatric body adiposity index (pBAI), a body shape index (ABSI), abdominal volume index (AVI), waist to height ratio (WtHR) and waist to hip ratio (WHR). Log transformations of each index adjusted for age and sex and IR were used for the linear regressions. Additionally, we generated receiver operating characteristics (ROC) from logistic regressions between HOMA-IR and HOMA2IR against the same indices.ResultsUsing the homeostatic assessment of insulin resistance (HOMA-IR), HOMA2IR, the quantitative insulin-sensitivity check index (QUICKI), fasting serum insulin, and FPG/FSI to measure IR, we showed that BMI adjusted for age and sex performs similarly to many of the newer indices in our sample. The correlation coefficients for pBAI [R2: 0.27, 95% confidence interval: 0.88–1.81, p &lt; 0.001] and BMI [R2: 0.27, 95% confidence interval: 0.92–1.92, p &lt; 0.001] were the highest for HOMA-IR. Similarly, pBAI [R2: 0.29, 95% confidence interval: 0.88–1.72, p &lt; 0.001] and BMI [R2: 0.29, 95% confidence interval: 0.93–1.83, p &lt; 0.001] were the highest for HOMA2IR. A similar trend was observed with QUICKI, FSI, and FPG/FSI. ABSI had the lowest R2 value for all measures of IR. Area under the curve (AUC) values for the receiver operating characteristics (ROC) for HOMA-IR and HOMA2IR support these conclusions.ConclusionsBMI adjusted for age and sex, despite its usage and simplicity, still stacks up well against newer indices in our Latino sample. Testing these indices across larger samples is necessary to generalize these findings and translate performance to adults.
Barriers to adherence to iron chelation therapy among adolescent with transfusion dependent thalassemia
Authors: Mohamed Rafaa , Abdul Rahman Amir Hamzah , Masra Farin , Abdul Latiff Zarina 
Published: October 2022

Study backgroundThalassemia is the commonest genetic blood disorder in Malaysia which requires life-long blood transfusions. From a total of 7,984 thalassemia patients in Malaysia, adolescent age group account for the highest number of patients (2,680 patients, 33.57%). In developed countries, the average rate of adherence to long-term treatment among children and adolescents is only 58%. Sub-optimal adherence to iron chelation therapy may impact the outcome and quality of life in these patients. Thus, assessing adherence level and identification of risk factors for non-adherence is essential in optimizing management.ObjectivesTo determine the association between mean serum ferritin level with self-reported level of adherence to iron chelation therapy in transfusion dependent thalassemia (TDT) adolescents in Hospital Tengku Ampuan Afzan (HTAA), Kuantan and Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Cheras; to determine the association between socio-demographic factors and patients’ knowledge on thalassemia and iron chelation therapy with the level of adherence.Materials and methodsThis was a cross-sectional study conducted between 1st March 2019 and 31st March 2020. Data was collected through face-to-face interview by a single interviewer during the thalassemia clinic follow up, with content validated questionnaires. The questionnaires comprised four sections which included socio-demographic data, medication adherence questionnaire, knowledge of disease, and clinical characteristics of the participants.ResultsA total of 70 participants were recruited. Results showed that only 51.4% of participants had good adherence to iron chelation therapy. There was a significant association between monthly household incomes of the family with the level of adherence to iron chelation (p-value 0.006). There was also an association between the mean serum ferritin levels with total Adherence Starts with Knowledge (ASK-12) score (p-value 0.001). However, there was no association between knowledge on thalassemia with the level of adherence.ConclusionAdherence to iron chelation was generally unsatisfactory amongst adolescents with TDT as only 51.4% had good adherence. Low monthly household income of the family may affect adherence to iron chelation therapy in TDT patients. As adherence remains to be an issue amongst adolescent thalassemia patients, management should include regular and objective assessments to address this problem so as to optimize patient outcome.
Network analysis and experimental pharmacology study explore the protective effects of Isoliquiritigenin on 5-fluorouracil-Induced intestinal mucositis
Authors: Liao Yi-fan , Luo Feng-lin , Tang Shan-shan , Huang Jing-wei , Yang Ying , Wang Shuang , Jiang Tang-yu , Man Qiong , Liu Sha , Wu Yi-ying 
Published: October 2022

5-fluorouracil (5-FU) is one of the most widely used chemotherapy drugs for malignant tumors. However, intestinal mucositis caused by 5-FU is a severe dose-limiting toxic effect and even leads to treatment interruption. Isoliquiritigenin (ISL) is one of the main active compounds of licorice, which is a traditional Chinese herbal medicine commonly used in inflammation and gastrointestinal diseases. It is speculated that ISL have protective effects on intestinal mucositis. However, no such studies have been reported. Therefore, to investigate the impact of ISL on 5-Fu-induced intestinal mucositis, a strategy based on network prediction and pharmacological experimental validation was proposed in this study. Firstly, the targets and mechanism of ISL in alleviating 5-Fu-induced gastrointestinal toxicity were predicted by network analysis. And the results were further confirmed by molecular docking. Then, a mouse model of intestinal mucositis was established by intraperitoneal injection of 5-FU (384 μmol/kg) to verify the prediction of network analysis. The network analysis results suggested that PTGS2 (Prostaglandin G/H synthase 2) and NOS2 (Nitric oxide synthase, inducible) might be the critical targets of ISL for reducing the intestinal toxicity of 5-FU. In addition, KEGG and GO enrichment analysis revealed that the HIF-1, TNF, MAPK, IL-17, PI3K-Akt, Ras, NF-kappa B signaling pathway, and biological processes of the inflammatory response, apoptosis regulation, NO production and NF-kappa B transcription factor activity might be involved in the mechanism of ISL against intestinal mucositis. Subsequent animal experiments showed that ISL could reduce the weight loss, leukopenia and mucosal damage caused by 5-FU. Compared with the intestinal mucositis model, the protein expressions of PTGS2, NOS2, TNFα (Tumor necrosis factor-alpha) and NF-κB p65 (nuclear factor kappa-B P65) were decreased after ISL treatment. In conclusion, this study is the fist time to find that ISL can attenuate 5-FU-induced intestinal mucositis in mice. Its anti-mucositis effect may be through regulating TNF/NF-κB pathway and inhibiting inflammatory mediators PTGS2 and NOS2. It will provide a potential candidate for the prevention and treatment of chemotherapy-induced intestinal mucositis.
Bibliometric analysis of research on immunogenic cell death in cancer
Authors: Zhou Yan , Hu Fen , Cui Yang , Wu Haiyang , Hu Shunan , Wei Wei 
Published: October 2022

Background: Immunotherapy is changing the way we treat cancer. Immunogenic cell death (ICD) has received considerable attention in the treatments of various cancer types, due to the long-lasting antitumor responses elicited in human body. However, to date, no relevant bibliometric research has been reported.Methods: Publications related to ICD in cancer research were collected from the Web of Science Core Collection. Using CiteSpace, VOSviewer and an online platform, the analyses of co-author, co-citation, and co-occurrence of terms retrieved from literatures were carried out.Results: A total of 1,577 publications were included in this study. The global research literatures on ICD in cancer research have been increasing from 2005 to 2021. China, the United States and France dominated in this area and had close collaborations with many countries. Six of the top 10 most contributive institutions were from France. When it comes to author analysis, Kroemer G, Zitvogel L, Kepp O, Garg AD and Galluzzi L were in both the top 10 most productive authors and top 10 most co-cited authors lists. The co-occurring author keywords could be grouped into three clusters: “biomarkers of ICD”, “nanoparticles” and “combination therapy”. In terms of promising hotspots, keywords (author keywords and KeyWords Plus) with recent citation bursts could be summarized into two aspects: “tumor microenvironment” and “nanoparticles”.Conclusion: Increased attention has been paid to ICD in cancer treatment. However, there are still many unresolved domains in the field of ICD, such as clinical application and molecular mechanisms of this cell death process. ICD-inducing modalities combined with nanotechnology could potentiate the current immunotherapies, and will be hotspots for future research.
Systemic triplet therapy for metastatic hormone-sensitive prostate cancer: A systematic review and network meta-analysis
Authors: Jian Tengteng , Zhan Yang , Hu Kebang , He Liang , Chen Sunmeng , Hu Rui , Lu Ji 
Published: October 2022

Purpose: To perform a systematic review and network meta-analysis to compare the efficacy and safety of currently available docetaxel-based systemic triplet therapies for metastatic hormone-sensitive prostate cancer (mHSPC).Methods: We searched for eligible publications in PubMed, Embase, and Cochrane CENTRAL. Improvements in overall survival (OS) and radiographic progression-free time (rPFS) were compared indirectly using network meta-analysis and evaluated using the surface under the cumulative ranking curve (SUCRA). Other secondary endpoints, such as time to castration-resistant prostate cancer and/or adverse events (AEs), were also compared and evaluated.Results: Five trials were selected and analyzed using a network meta-analysis. Compared to androgen deprivation therapy (ADT) plus docetaxel, darolutamide (hazard ratio [HR]: 0.68, 95% credible interval [CrI]: 0.57–0.80) and abiraterone (HR: 0.75, 95% CrI: 0.59–0.95) triplet therapy had significantly longer OS, and darolutamide triplet therapy was the first treatment ranked. Abiraterone (HR: 0.49, 95% CrI: 0.39–0.61) and enzalutamide (HR: 0.52, 95% CrI: 0.30–0.89) had significantly better rPFS than ADT plus docetaxel; however, all three therapies, including abiraterone, apalutamide, and enzalutamide, were the best options with a similar SUCRA. At most secondary endpoints, systemic triplet therapy was superior to ADT plus docetaxel. The risk of any AEs in darolutamide or abiraterone triplet therapy was comparable with ADT plus docetaxel (odds ratio [OR]: 2.53, 95% credible interval [CrI]: 0.68–12.63; OR: 1.07, 95% CrI: 0.03–36.25). Abiraterone triplet therapy had an increased risk of grade≥3 AEs (OR: 1.56, 95% CrI: 1.15–2.11).Conclusion: Systemic triplet therapy was more effective than ADT plus docetaxel for mHSPC. Of the triplet therapy regimens, darolutamide ranked first in terms of improved OS. Abiraterone and enzalutamide triplet ranked first in terms of rFPS, however, it did not confer a statistically difference among all triplet regimens. The overall risk of AEs was comparable. More studies are required for current and potential combinations of systemic triplet therapy.
Aldosterone-stimulated endothelial epithelial sodium channel (EnNaC) plays a role in cold exposure–induced hypertension in rats
Authors: Tang Liang-Liang , Yang Xu , Yu Shu-Qi , Qin Qi , Xue Rong , Sun Yu , Xiao Han , Shang An-Qi , Liu Jia-Qun , Han Song-Qi , Liang Chen , Lou Jie , Wang Qiu-Shi , Yu Chang-Jiang , Wu Ming-Ming , Zhang Zhi-Ren 
Published: October 2022

Background: Previous studies have demonstrated that activated endothelial epithelial sodium channel (EnNaC) impairs vasodilatation, which contributes to salt-sensitive hypertension. Here, we investigate whether mesenteric artery (MA) EnNaC is involved in cold exposure–induced hypertension (CIH) and identify the underlying mechanisms in SD rats.Methods: One group of rats was housed at room temperature and served as control. Three groups of rats were kept in a 4°C cold incubator for 10 h/day; among which two groups were administrated with either benzamil (EnNaC blocker) or eplerenone (mineralocorticoid receptor antagonist, MR). Blood pressure (BP), vasodilatation, and endothelial function were measured with tail-cuff plethysmography, isometric myograph, and Total Nitric Oxide (NO) Assay kit, respectively. A cell-attached patch-clamp technique, in split-open MA, was used to determine the role of EnNaC in CIH rats. Furthermore, the plasma aldosterone levels were detected using an ELISA kit; and Western blot analysis was used to examine the relative expression levels of Sgk1 and Nedd4-2 proteins in the MA of SD rats.Results: We demonstrated that cold exposure increased BP, impaired vasodilatation, and caused endothelial dysfunction in rats. The activity of EnNaC significantly increased, concomitant with an increased level of plasma aldosterone and activation of Sgk1/Nedd4-2 signaling. Importantly, CIH was inhibited by either eplerenone or benzamil. It appeared that cold-induced decrease in NO production and impairment of endothelium-dependent relaxation (EDR) were significantly ameliorated by either eplerenone or benzamil in MA of CIH rats. Moreover, treatment of MAs with aldosterone resulted in an activation of EnNaC, a reduction of NO, and an impairment of EDR, which were significantly inhibited by either eplerenone or GSK650394 (Sgk1 inhibitor) or benzamil.Conclusion: Activation of EnNaC contributes to CIH; we suggest that pharmacological inhibition of the MR/Sgk1/Nedd4-2/EnNaC axis may be a potential therapeutic strategy for CIH.
Detection of endo-epicardial atrial low-voltage areas using unipolar and omnipolar voltage mapping
Authors: Van Schie Mathijs S. , Knops Paul , Zhang Lu , Van Schaagen Frank R. N. , Taverne Yannick J. H. J. , De Groot Natasja M. S. 
Published: October 2022

Background: Low-voltage areas (LVA) can be located exclusively at either the endocardium or epicardium. This has only been demonstrated for bipolar voltages, but the value of unipolar and omnipolar voltages recorded from either the endocardium and epicardium in predicting LVAs at the opposite layer remains unknown. The goal of this study was therefore to compare simultaneously recorded endo-epicardial unipolar and omnipolar potentials and to determine whether their voltage characteristics are predictive for opposite LVAs.Methods: Intra-operative simultaneous endo-epicardial mapping (256 electrodes, interelectrode distances 2 mm) was performed during sinus rhythm at the right atrium in 93 patients (67 ± 9 years, 73 male). Cliques of four electrodes (2 × 2 mm) were used to define maximal omnipolar (Vomni,max) and unipolar (Vuni,max) voltages. LVAs were defined as Vomni,max ≤0.5 mV or Vuni,max ≤1.0 mV.Results: The majority of both unipolar and omnipolar LVAs were located at only the endocardium (74.2% and 82.0% respectively) or epicardium (52.7% and 47.6% respectively). Of the endocardial unipolar LVAs, 25.8% were also located at the opposite layer and 47.3% vice-versa. In omnipolar LVAs, 18.0% of the endocardial LVAs were also located at the epicardium and 52.4% vice-versa. The combination of epicardial Vuni,max and Vomni,max was most accurate in identifying dual-layer LVAs (50.4%).Conclusion: Unipolar and omnipolar LVAs are frequently located exclusively at either the endocardium or epicardium. Endo-epicardial LVAs are most accurately identified using combined epicardial unipolar and omnipolar voltages. Therefore, a combined endo-epicardial unipolar and omnipolar mapping approach is favoured as it may be more indicative of possible arrhythmogenic substrates.