bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of ultrasound−based ADNEX model with magnetic resonance imaging for discriminating adnexal masses: a multi-center study
Authors: Hu Yanli , Chen Bo , Dong Hongmei , Sheng Bo , Xiao Zhibo , Li Jia , Tian Wei , Lv Furong 
Published: April 2023

ObjectivesThe ADNEX model offered a good diagnostic performance for discriminating adnexal tumors, but research comparing the abilities of the ADNEX model and MRI for characterizing adnexal tumors has not been reported to our knowledge. The aim of this study was to evaluate the diagnostic accuracy of the ultrasound-based ADNEX (Assessment of Different NEoplasias in the adneXa) model in comparison with that of magnetic resonance imaging (MRI) for differentiating benign, borderline and malignant adnexal masses.MethodsThis prospective study included 529 women with adnexal masses who underwent assessment via the ADNEX model and subjective MRI analysis before surgical treatment between October 2019 and April 2022 at two hospitals. Postoperative histological diagnosis was considered the gold standard.ResultsAmong the 529 women, 92 (17.4%) masses were diagnosed histologically as malignant tumors, 67 (12.7%) as borderline tumors, and 370 (69.9%) as benign tumors. For the diagnosis of malignancy, including borderline tumors, overall agreement between the ADNEX model and MRI pre-operation was 84.9%. The sensitivity of the ADNEX model of 0.91 (95% confidence interval [CI]: 0.85–0.95) was similar to that of MRI (0.89, 95% CI: 0.84–0.94; P=0.717). However, the ADNEX model had a higher specificity (0.90, 95% CI: 0.87–0.93) than MRI (0.81, 95% CI: 0.77–0.85; P=0.001). The greatest sensitivity (0.96, 95% CI: 0.92–0.99) and specificity (0.94, 95% CI: 0.91–0.96) were achieved by combining the ADNEX model and subjective MRI assessment. While the total diagnostic accuracy did not differ significantly between the two methods (P=0.059), the ADNEX model showed greater diagnostic accuracy for borderline tumors (P&lt;0.001).ConclusionThe ultrasound-based ADNEX model demonstrated excellent diagnostic performance for adnexal tumors, especially borderline tumors, compared with MRI. Accordingly, we recommend that the ADNEX model, alone or with subjective MRI assessment, should be used for pre-operative assessment of adnexal masses.
ERBB family fusions are recurrent and actionable oncogenic targets across cancer types
Authors: Schubert Laura , Elliott Andrew , Le Anh T. , Estrada-Bernal Adriana , Doebele Robert C. , Lou Emil , Borghaei Hossein , Demeure Michael J. , Kurzrock Razelle , Reuss Joshua E. , Ou Sai-Hong Ignatius , Braxton David R. , Thomas Christian A. , Darabi Sourat , Korn Wolfgang Michael , El-Deiry Wafik S. , Liu Stephen V. 
Published: April 2023

PurposeGene fusions involving receptor tyrosine kinases (RTKs) define an important class of genomic alterations with many successful targeted therapies now approved for ALK, ROS1, RET and NTRK gene fusions. Fusions involving the ERBB family of RTKs have been sporadically reported, but their frequency has not yet been comprehensively analyzed and functional characterization is lacking on many types of ERBB fusions.Materials and methodsWe analyzed tumor samples submitted to Caris Life Sciences (n=64,354), as well as the TCGA (n=10,967), MSK IMPACT (n=10,945) and AACR GENIE (n=96,324) databases for evidence of EGFR, ERBB2 and ERBB4 gene fusions. We also expressed several novel fusions in cancer cell lines and analyzed their response to EGFR and HER2 tyrosine kinase inhibitors (TKIs).ResultsIn total, we identified 1,251 ERBB family fusions, representing an incidence of approximately 0.7% across all cancer types. EGFR, ERBB2, and ERBB4 fusions were most frequently found in glioblastoma, breast cancer and ovarian cancer, respectively. We modeled two novel types of EGFR and ERBB2 fusions, one with a tethered kinase domain and the other with a tethered adapter protein. Specifically, we expressed EGFR-ERBB4, EGFR-SHC1, ERBB2-GRB7 and ERBB2-SHC1, in cancer cell lines and demonstrated that they are oncogenic, regulate downstream signaling and are sensitive to small molecule inhibition with EGFR and HER2 TKIs.ConclusionsWe found that ERBB fusions are recurrent mutations that occur across multiple cancer types. We also establish that adapter-tethered and kinase-tethered fusions are oncogenic and can be inhibited with EGFR or HER2 inhibitors. We further propose a nomenclature system to categorize these fusions into several functional classes.
Terminal fucosylation of haptoglobin in cancer-derived exosomes during cholangiocarcinoma progression
Authors: Choi Hyewon , Ju Sungeun , Kang Keunsoo , Seo Moon-Hyeong , Kim Jin-Man , Miyoshi Eiji , Yeo Min-Kyung , Park Seung-Yeol 
Published: April 2023

BackgroundCholangiocarcinoma (CCA) is a silent tumor with a high mortality rate due to the difficulty of early diagnosis and prediction of recurrence even after timely surgery. Serologic cancer biomarkers have been used in clinical practice, but their low specificity and sensitivity have been problematic. In this study, we aimed to identify CCA-specific glycan epitopes that can be used for diagnosis and to elucidate the mechanisms by which glycosylation is altered with tumor progression.MethodsThe serum of patients with various cancers was fractioned into membrane-bound and soluble components using serial ultracentrifugation. Lectin blotting was conducted to evaluate glycosylation. Proteins having altered glycosylation were identified using proteomic analysis and further confirmed using immunoblotting analysis. We performed HPLC, gene analysis, real-time cargo tracking, and immunohistochemistry to determine the origin of CCA glycosylation and its underlying mechanisms. Extracellular vesicles (EV) were isolated from the sera of 62 patients with CCA at different clinical stages and inflammatory conditions and used for glycan analysis to assess their clinical significance.ResultsThe results reveal that glycosylation patterns between soluble and membrane-bound fractions differ significantly even when obtained from the same donor. Notably, glycans with α1-3/4 fucose and β1-6GlcNAc branched structures increase specifically in membrane-bound fractions of CCA. Mechanically, it is primarily due to β-haptoglobin (β-Hp) originating from CCA expressing fucosyltransferase-3/4 (FUT 3/4) and N-acetylglucosaminyltransferase-V (MGAT5). Newly synthesized β-Hp is loaded into EVs in early endosomes via a KFERQ-like motif and then secreted from CCA cells to induce tumor progression. In contrast, β-Hp expressed by hepatocytes is secreted in a soluble form that does not affect CCA progression. Moreover, evaluation of EV glycosylation in CCA patients shows that fucosylation level of EV-Hp gradually increases with tumor progression and decreases markedly when the tumors are eliminated by surgery.ConclusionThis study suggests that terminal fucosylation of Hp in cancer-derived exosomes can be a novel glycan marker for diagnosis and prognosis of CCA. These findings highlight the potential of glycan analysis in different fractions of serum for biomarker discover for other diseases. Further research is needed to understand the role of fucosylated EVs on CCA progression.
Youth baseline and state pain-related injustice appraisals are associated with emotional responses of anger and sadness: An experimental study
Authors: Daenen Frederick , Wauters Aline , Van Ryckeghem Dimitri M.L. , Trost Zina , Vervoort Tine 
Published: April 2023

BackgroundYouth pain-related injustice appraisals are associated with adverse functioning; however, mechanisms by which injustice appraisals exert their impact have yet to be elucidated. Adult injustice literature suggests anger, sadness, and attention bias to anger (AB) as potential mechanisms. This study examined the effects of injustice appraisals in a healthy youth sample by applying a justice violation manipulation. We hypothesized the justice violation condition to lead to worse pain outcomes with effects mediated by anger, sadness, and AB as compared to the control condition. We further explored associations between both baseline and state injustice appraisals and anger, sadness, and AB across conditions.MethodsA 2 × 2 time by condition design was used to test hypotheses. 133 healthy youth aged 9–16 years old completed two cold pressor tasks (CPTs). In the experimental (i.e., justice violation) group, participants were initially told to complete one CPT, but were told afterwards to perform it again due to experimenter negligence. In the control group, no justice violation occurred. Baseline injustice appraisals and pain catastrophizing were assessed with the Injustice Experience Questionnaire and Pain Catastrophizing Scale for Children; state outcomes (i.e., injustice, catastrophizing, anger, sadness) were assessed after CPTs. AB was indexed using a dot-probe task.ResultsFindings indicated no effects of the justice violation on pain outcomes or associated mechanisms, nor on injustice appraisals, suggesting manipulation failure. However, across conditions, baseline and state injustice appraisals were positively associated with anger and sadness, but not with AB.ConclusionsDespite the experimental justice violation failing to elicit differential injustice appraisals across conditions, the current study supports both anger and sadness as key emotional responses associated with pain-related injustice appraisals in a healthy youth sample.
Value assessment of PD-1/PD-L1 inhibitors in the treatment of oesophageal and gastrointestinal cancers
Authors: Ou Shun-Long , Luo Jing , Wei Hua , Qin Xiao-Li , Jiang Qian 
Published: April 2023

Background: Evidence of efficacy and safety of programmed cell death 1 (PD-1) and programmed death ligand-1 (PD-L1) checkpoint inhibitors in oesophageal cancer (EC), gastric cancer (GC) and colorectal cancer (CRC) was inconsistent, obscuring their clinical application and decision-making. The aim of this study was to comprehensively evaluate the value of PD-1/PD-L1 inhibitors in EC, GC and CRC to select valuable PD-1/PD-L1 inhibitors, and to assess the association between the value and cost of PD-1/PD-L1 inhibitors.Methods: A comprehensive search of trials of PD-1/PD-L1 inhibitors in EC, GC and CRC was performed in Chinese and English medical databases with a cut-off date of 1 July 2022. Two authors independently applied the ASCO-VF and ESMO-MCBS to assess the value of PD-1/PD-L1 inhibitors. A receiver operating characteristic (ROC) curve was generated to establish the predictive value of the ASCO-VF score to meet the threshold of the ESMO-MCBS grade. Spearman’s correlation was used to calculate the relationship between the cost and value of drugs.Results: Twenty-three randomized controlled trials were identified: ten (43.48%) in EC, five (21.74%) in CRC, and eight (34.78%) in GC or gastroesophageal junction cancer (GEJC). For advanced diseases, ASCO-VF scores ranged from −12.5 to 69, with a mean score of 26.5 (95% CI 18.4–34.6). Six (42.9%) therapeutic regimens met the ESMO-MCBS benefit threshold grade. The area under the ROC curve was 1.0 (p = 0.002). ASCO-VF scores and incremental monthly cost were negatively correlated (Spearman’s ρ = −0.465, p = 0.034). ESMO-MCBS grades and incremental monthly cost were negatively correlated (Spearman’s ρ = −0.211, p = 0.489).Conclusion: PD-1/PD-L1 inhibitors did not meet valuable threshold in GC/GEJC. Pembrolizumab met valuable threshold in advanced microsatellite instability–high CRC. The value of camrelizumab and toripalimab may be more worth paying in EC.
The safety concerns regarding immune checkpoint inhibitors in liver cancer patients rising mainly from CHB
Authors: Lou Shike , Cao Zhujun , Chi Wanqing , Wang Xiaoyin , Feng Mingyang , Lin Lanyi , Ding Yezhou , Liu Kehui , Qu Lihong , Zhao Gangde , Bao Shisan , Wang Hui 
Published: April 2023

Aim: To analyze the safety of immune checkpoint inhibitors in primary liver cancer patients and to identify the risk factors for immune-related adverse events (irAEs).Methods: The study enrolled 106 patients with primary liver cancer, including 81 with hepatocellular carcinoma and 25 with intrahepatic cholangiocarcinoma. We analyzed the differences between groups in irAE occurrence, including those with and without targeted drugs and those who received interventional therapy.Results: The incidence of irAEs was 39%, with thyroid function, liver function, and skin events being the most common. There was no correlation among irAE incidence and the liver cancer type, stage, or severity; grade of Child–Pugh score; and Barcelona Clinical Liver Cancer classification. However, being overweight was a significant risk factor for irAEs, correlating with high body mass index. The combination of targeted drugs and/or transcatheter arterial chemoembolization therapy did not increase the incidence of irAEs.Conclusion: Being overweight is a potential risk factor for irAEs in primary liver cancer patients. However, there is no correlation between irAE incidence and the liver cancer type, stage, or severity or a combination of targeted drugs or transarterial chemoembolization therapy.
Protective effects of ginsenosides Rg1 and Rb1 against cognitive impairment induced by simulated microgravity in rats
Authors: Jiang Ning , Lv Jingwei , Zhang Yiwen , Sun Xinran , Yao Caihong , Wang Qiong , He Qinghu , Liu Xinmin 
Published: April 2023

Microgravity experienced during space flight is known to exert several negative effects on the learning ability and memory of astronauts. Few effective strategies are currently available to counteract these effects. Rg1 and Rb1, the major steroidal components of ginseng, have shown potent neuroprotective effects with a high safety profile. The present study aimed to investigate the effects of Rg1 and Rb1 on simulated microgravity-induced learning and memory dysfunction and its underlying mechanism in the hindlimb suspension (HLS) rat model. Administration of Rg1 (30 and 60 μmol/kg) and Rb1 (30 and 60 μmol/kg) for 2 weeks resulted in a significant amelioration of impaired spatial and associative learning and memory caused by 4-week HLS exposure, measured using the Morris water maze and Reward operating conditioning reflex (ROCR) tests, respectively. Furthermore, Rg1 and Rb1 administration alleviated reactive oxygen species production and enhanced antioxidant enzyme activities in the prefrontal cortex (PFC). Rg1 and Rb1 also assisted in the recovery of mitochondrial complex I (NADH dehydrogenase) activities, increased the expression of Mfn2 and decreased the fission marker dynamin-related protein (Drp)-1expression. Additionally, Rg1 and Rb1 treatment increased the SYN, and PSD95 protein expressions and decreased the ratio of Bax:Bcl-2 and reduced the expression of cleaved caspase-3 and cytochrome C. Besides these, the BDNF-TrkB/PI3K-Akt pathway was also activated by Rg1 and Rb1 treatment. Altogether, Rg1 and Rb1 treatment attenuated cognitive deficits induced by HLS, mitigated mitochondrial dysfunction, attenuated oxidative stress, inhibited apoptosis, increased synaptic plasticity, and restored BDNF-TrkB/PI3K-Akt signaling.
Effect of the combination of 25-hydroxyvitamin D3 and higher level of calcium and phosphorus in the diets on bone 3D structural development in pullets
Authors: White Dima , Chen Chongxiao , Kim Woo Kyun 
Published: April 2023

Bone issues such as osteoporosis are major concerns for the laying hen industry. A study was conducted to improve bone-health in pullets. A total of 448 one-day-old Hyline W36 pullets were randomly assigned to four treatments (8 rep; 14 birds/rep) until 17 weeks (wks). Dietary treatments were: 1) vitamin D3 at (2,760 IU/kg) (D), 2) vitamin D3 (2,760 IU/kg)+62.5 mg 25-(OH)D3/ton (H25D), 3) vitamin D3 (2,760 IU/kg) + 62.5 mg 25-(OH)D3/ton + high Ca&amp;P (H25D + Ca/P), and 4) vitamin D3 (2,760 IU/kg) + high Ca&amp;P (D + Ca/P). The high calcium (Ca) and phosphorus (P) diet was modified by increasing both high calcium and phosphorus by 30% (2:1) for the first 12 wks and then only increasing P for 12–17 wks to reduce the Ca to P ratio. At 17 wk, growth performance was measured, whole body composition was measured by dual energy x-ray absorptiometry (DEXA), and femur bones were scanned using Micro-computed tomography (Micro-CT) for bone 3D structure analyses. The data were subjected to a one-way ANOVA using the GLM procedure, with means deemed significant at p &lt; 0.05. There was no significant outcome for growth performance or dual energy x-ray absorptiometry parameters. Micro-computed tomography results indicated that the H25D + Ca/P treatment had lower open pore volume space, open porosity, total volume of pore space, and total porosity in the cortical bone compared to the D + Ca/P. It also showed that a higher cortical bone volume/tissue volume (BV/TV) in the H25D + Ca/P than in the D + Ca/P. Furthermore, the H25D + Ca/P treatment had the lowest trabecular pattern factor and structure model index compared to the other treatments, which indicates its beneficial effects on trabecular structural development. Moreover, the H25D + Ca/P had a higher trabecular percentage compared to the D and 25D, which suggests the additional high calcium and phosphorus supplementation on top of 25D increased trabecular content in the cavity. In conclusion, the combination of 25D with higher levels of high calcium and phosphorus could improve cortical bone quality in pullets and showed a beneficial effect on trabecular bone 3D structural development. Thus, combination of a higher bio-active form of vitamin D3 and higher levels of high calcium and phosphorus could become a potential feeding strategy to improve bone structural integrity and health in pullets.
Ultrasound assessments of organs and blood vessels before and after 40 days isolation in a cavern (deep time experiment 2021)
Authors: Arbeille Philippe , Zuj Kathryn A. , Besnard Stephane , Mauvieux Benoit , Hingrand Corentin , Delaunay Pierre-Louis , Hughson Richard L. , Clot Christian 
Published: April 2023

Introduction: Spaceflight simulation studies like confinement in small volume habitat with limited physical activity have reported even after 60 days an abnormal arterial wall adaptation with increase thickness or stiffness. The purpose of the current study was to determine the effects on blood vessel and organ structure of 40 days of isolation in a huge habitat with intensive physical activity.Method: Data were collected from 14 individuals (7 male) who isolated in a cavern for 40-days while performing normal daily activities without time references. Ultrasound assessments were performed pre- and post-isolation using a teleoperated system with eight different acoustic windows to obtain 19 measurements on 12 different organ/vascular structures which included the common carotid artery, femoral artery, tibial artery, jugular vein, portal vein, bile duct, kidney, pancreas, abdominal aorta, cervical and lumbar vertebral distance, and Achilles tendon.Results: Common carotid artery measures, including the intima media thickness, stiffness index, and the index of reflectivity measured from the radiofrequency signal, were not changed with isolation. Similarly, no differences were found for femoral artery measurements or measurements of any of the other organs/vessels assessed. There were no sex differences for any of the assessments.Discussion: Results from this study indicate a lack of physiological effects of 40-days of isolation in a cavern, contrary to what observed in previous 60 days confinement. This suggests a potential protective effect of sustained physical activity, or reduced environmental stress inside the huge volume of the confined facility.
Out-of-season spawning of largemouth bass in a controllable recirculating system
Authors: Hu Chen-Hao , Bie Han-Qing , Lu Zi-Yi , Ding Yang , Guan He-He , Geng Long-Hui , Ma Shuai , Hu Yuan-Xiang , Fan Qi-Xue , Shen Zhi-Gang 
Published: April 2023

Largemouth bass (LMB) production exceeded 0.7 million tons in 2021 and has become one of the most important freshwater aquaculture species in China. The stable and fixed culture cycle led to regular and drastic price fluctuation during the past decade. Strong price fluctuation provides opportunities and challenges for the LMB industry, and out-of-season spawning (OSS) and culture will provide technical support for the opportunities. To induce OSS at a low cost, we established a controllable recirculating system that allows precise thermo-photoperiod manipulation. In the system, four experimental groups were assigned, 18NP (18°C overwintering water temperature, natural photoperiod), 18CP (18°C overwintering water temperature, controlled photoperiod), 16CP (16°C overwintering water temperature, controlled photoperiod), and NTNP (natural water temperature and natural photoperiod), to determine the effects of chilling temperature and photoperiod on spawning performance. OSS was observed in all the experimental groups without significant differences, except NTNP. The manipulated broodstock can re-spawn 3 months later in the next spring in advance. Further analysis of the volume percentage of different stages of oocytes provides a base for excellent regression between the volume percentage of the primary growth stage, cortical alveoli stage, vitellogenesis/maturation stage, and gonadal development/maturation. The results suggest that the volume percentage of oocytes is a better indicator of gonadal development and maturation than the gonadosomatic index. We also found that LMB prefers palm fiber as a spawning nest over gravel. The findings of this work provide important technique guidance for practical OSS of the LMB aquaculture industry and standardization of ovary development and maturation in fish with asynchronous developmental oocytes.