bluuebunny/crossref_metadata_2025_split huggingface dataset:
INSTIGO Trial: Evaluation of a Plasma Protein Profile as a Predictive Biomarker for Metastatic Relapse of Triple Negative Breast Cancer
Authors: Veyssière Hugo , Lusho Sejdi , Molnar Ioana , Kossai Myriam , Bernadach Maureen , Abrial Catherine , Bidet Yannick , Radosevic-Robin Nina , Durando Xavier 
Published: June 2021

BackgroundTriple negative breast cancer (TNBC) accounts for 10-20% of breast cancers but has no specific therapy. While TNBC may be more sensitive to chemotherapy than other types of breast cancer, it has a poor prognosis. Most TNBC relapses occur during the five years following treatment, however predictive biomarkers of metastatic relapse are still lacking. High tumour-infiltrating lymphocytes (TILs) levels before and after neo-adjuvant chemotherapy (NAC) are associated with lower relapse risk and longer survival but TILs assessment is highly error-prone and still not introduced into the clinic. Therefore, having reliable biomarker of relapse, but easier to assess, remains essential for TNBC management. Searching for such biomarkers among serum/plasma proteins, circulating tumoral DNA (ctDNA) and blood cells appear relevant.MethodsThis single-centre and prospective study aims to discover predictive biomarkers of TNBC relapse and particularly focuses on plasma proteins. Blood samples will be taken at diagnosis, on the day of first-line or post-NAC surgery, on the day of radiotherapy start, then 6 months and one year after radiotherapy. A blood sample will be taken at the time of metastatic relapse diagnosis. Blood samples will be used for circulating protein quantification, blood cell counts and circulating tumour DNA quantification. A tumour RNA signature, based on the analysis of the RNA expression of 6 genes, will also be tested from the initial biopsy taken routinely. In NAC patients, TILs quantity will be assessed on TNBC pre-treatment biopsy and surgical specimen.Ethics and DisseminationINSTIGO belongs to category 2 interventional research on humans. This study has been approved by the SUD-EST IV ethics committee and is conducted in accordance with the Declaration of Helsinki and General Data Protection Regulation (GDPR). Study findings will be published in peer-reviewed medical journals.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT04438681.
Comparison of Diagnostic Performance of Spread Through Airspaces of Lung Adenocarcinoma Based on Morphological Analysis and Perinodular and Intranodular Radiomic Features on Chest CT Images
Authors: Qi Lin , Li Xiaohu , He Linyang , Cheng Guohua , Cai Yongjun , Xue Ke , Li Ming 
Published: June 2021

ObjectSTAS is associated with poor differentiation, KRAS mutation and poor recurrence-free survival. The aims of this study are to evaluate the ability of intra- and perinodular radiomic features to distinguish STAS at non-contrast CT.Patients and MethodsThis retrospective study included 216 patients with pathologically confirmed lung adenocarcinoma (STAS+, n = 56; STAS−, n = 160). Texture-based features were extracted from intra- and perinodular regions of 2, 4, 6, 8, 10, and 20 mm distances from the tumor edge using an erosion and expansion algorithm. Traditional radiologic features were also analyzed including size, consolidation tumor ratio (CTR), density, shape, vascular change, cystic airspaces, tumor–lung interface, lobulation, spiculation, and satellite sign. Nine radiomic models were established by using the eight separate models and a total of the eight VOIs (eight-VOI model). Then the prediction efficiencies of the nine radiomic models were compared to predict STAS of lung adenocarcinomas.ResultsAmong the traditional radiologic features, CTR, unclear tumor–lung interface, and satellite sign were found to be associated with STAS significantly, and the AUCs were 0.796, 0.677, and 0.606, respectively. Radiomic model of combined tumor bodies and all the distances of perinodular areas (eight-VOI model) had better predictive efficiency for predicting STAS+ lung adenocarcinoma. The AUCs of the eight-VOI model in the training and verification sets were 0.907 (95%CI, 0.862–0.947) in the training set, and 0.897 (95%CI, 0.784–0.985) in the testing set, and 0.909 (95%CI, 0.863–0.949) in the external validation set, and the diagnostic accuracy in the external validation set was 0.849.ConclusionRadiomic features from intra- and perinodular regions of nodules can best distinguish STAS of lung adenocarcinoma.
Radiomics Analysis of Contrast-Enhanced CT Predicts Survival in Clear Cell Renal Cell Carcinoma
Authors: Yan Lei , Yang Guangjie , Cui Jingjing , Miao Wenjie , Wang Yangyang , Zhao Yujun , Wang Ning , Gong Aidi , Guo Na , Nie Pei , Wang Zhenguang 
Published: June 2021

PurposeTo develop and validate the radiomics nomogram that combines clinical factors and radiomics features to estimate overall survival (OS) in patients with clear cell renal cell carcinoma (ccRCC), and assess the incremental value of radiomics for OS estimation.Materials and MethodsOne hundred ninety-four ccRCC cases were included in the training cohort and 188 ccRCC patients from another hospital as the test cohort. Three-dimensional region-of-interest segmentation was manually segmented on multiphasic contrast-enhanced abdominal CT images. Radiomics score (Rad-score) was calculated from a formula generated via least absolute shrinkage and selection operator (LASSO) Cox regression, after which the association between the Rad-score and OS was explored. The radiomics nomogram (clinical factors + Rad-score) was developed to demonstrate the incremental value of the Rad-score to the clinical nomogram for individualized OS estimation, which was then evaluated in relation to calibration and discrimination.ResultsRad-score, calculated using a linear combination of the 11 screened features multiplied by their respective LASSO Cox coefficients, was significantly associated with OS. Calibration curves showed good agreement between the OS predicted by the nomograms and observed outcomes. The radiomics nomogram presented higher discrimination capability compared to clinical nomogram in the training (C-index: 0.884; 95% CI: 0.808–0.940 vs. 0.803; 95% CI: 0.705–0.899, P &lt; 0.05) and test cohorts (C-index: 0.859; 95% CI: 0.800–0.921 vs. 0.846; 95% CI: 0.777–0.915, P &lt; 0.05).ConclusionsThe radiomics nomogram may be used for predicting OS in patients with ccRCC, and radiomics is useful to assist quantitative and personalized treatment.
ASRGL1 Correlates With Immune Cell Infiltration in Hepatocellular Carcinoma and Can Serve as a Prognostic Biomarker
Authors: Xue Cailin , Gao Peng , Cui Xiaohan , Zhang Xudong , Lei Jin , Li Renzhi , Zhu Chunfu , Qin Xihu 
Published: June 2021

BackgroundThe enzyme L-asparaginase (ASRGL1) catalyzes the hydrolysis of L-asparagine (Asn) to L-aspartic acid (Asp) and ammonia. Numerous studies have shown a strong correlation between ASRGL1 expression and tumorigenesis. However, the expression and biological function of ASRGL1 in hepatocellular carcinoma (HCC) are still unclear.MethodsWe explored the mRNA expression of ASRGL1 in HCC using the HCCDB, Oncomine, and TIMER 2.0 databases. Western blotting and immunohistochemical analyses were also used to determine the mRNA expression of ASRGL1 in HCC. LinkedOmics was used to analyze the genes co-expressed with ASRGL1 and regulators including kinases, miRNAs, and transcription factors. The Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the co-expressed genes were also investigated using LinkedOmics. The correlation between ASRGL1 expression and immune infiltrates was analyzed using the TIMER 2.0 and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The effects of ASRGL1 expression on patient outcome were investigated using the UALCAN and GEPIA databases, and the Kaplan–Meier plotter. c-Bioportal was used to explore the mutations of ASRGL1 in HCC.ResultsCompared with the adjacent tissues, ASRGL1 was upregulated in HCC. High ASRGL1 expression in HCC indicated poor relapse-free survival, progression-free survival, disease-specific survival, and overall survival. The expression of ASRGL1 was significantly correlated with infiltrating levels of B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC.ConclusionOur findings suggest that ASRGL1 is overexpressed in HCC and that ASRGL1 expression was significantly correlated with immune infiltration in HCC and prognosis. Therefore, ASRGL1 may serve as a biomarker for the early diagnosis and treatment of HCC.
Survival, Chemotherapy and Chemosensitivity Predicted by CTC Cultured In Vitro of SCLC Patients
Authors: Ju Lixia , Yang Juan , Zhai Changyun , Chai Shuizhen , Dong Zhiyi , Li Minghua 
Published: June 2021

PurposeThe prognosis for small cell lung cancer (SCLC) patients receiving later-line treatment is very poor and there is still no standard treatments after the second-line setting. Analyzing the susceptibility of chemotherapeutic drugs with circulating tumor cells (CTCs) cultured in vitro may contribute to optimize the therapeutic regimen. However, so far CTCs have been barely used for studying their chemosensitivity due to the lack of technology to obtain wholly intact and viable CTCs.MethodsBased on a retrospective study of the therapeutic response of 99 patients with unresectable SCLC, the CTC count in 14 SCLC patients was detected before and after chemotherapy to evaluate its role as a potential marker of response. Furthermore, the drug susceptibility of CTCs cultured in vitro obtained from ClearCell FX® System was tested and the therapy response was evaluated.ResultsAll of the 99 patients received the first-line chemotherapy and the objective response rate (ORR) was 74.7%. A total of 36 patients received the second-line therapy and the average duration was 2.6 months, and only 11 cases out of them received the third-line therapy but no one responded. The change of CTC counts was identified to be correlated with therapy response. However all the five SCLC patients who were administered with the drugs according to the drug susceptibility test of CTCs for two cycles underwent progression of disease.ConclusionThe results showed that the responses of chemotherapy are very poor in later lines and the drug susceptibility test using CTCs primary cultured in vitro may not benefit the improvement of therapeutic regimen of SCLC patients.
68Ga-FAPI-04 Versus 18F-FDG PET/CT in the Detection of Hepatocellular Carcinoma
Authors: Wang Hao , Zhu Wenwei , Ren Shuhua , Kong Yanyan , Huang Qi , Zhao Jun , Guan Yihui , Jia Huliang , Chen Jinhong , Lu Lu , Xie Fang , Qin Lunxiu 
Published: June 2021

BackgroundFibroblast activation protein (FAP) is commonly expressed in activated stromal fibroblasts in various epithelial tumours. Recently, 68Ga-FAPI-04 has been used for tumour imaging in positron emission tomography/computed tomography (PET/CT). This study aimed to compare the diagnostic performances of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in hepatocellular carcinoma (HCC), and to assess factors associated with 68Ga-FAPI-04 uptake in HCC.Materials and MethodsTwenty-nine patients with suspiciously HCC who received both 18F-FDG and 68Ga-FAPI-04 PET/CT were included in this retrospective study. The results were interpreted by two experienced nuclear medicine physicians independently. The maximum and mean standardized uptake values (SUVmax and SUVmean) were measured in the lesions and liver background, respectively. The tumour-to-background ratio (TBR) was then calculated as lesion’s SUVmax divided by background SUVmean.ResultsA total of 35 intrahepatic lesions in 25 patients with HCC were finally involved in the statistical analysis. 68Ga-FAPI-04 PET/CT showed a higher sensitivity than 18F-FDG PET/CT in detecting intrahepatic HCC lesions (85.7% vs. 57.1%, P = 0.002), including in small (≤ 2 cm in diameter; 68.8% vs. 18.8%, P = 0.008) and well- or moderately-differentiated (83.3% vs. 33.3%, P = 0.031) tumors. SUVmax was comparable between 68Ga-FAPI-04 and 18F-FDG (6.96 ± 5.01 vs. 5.89 ± 3.38, P &gt; 0.05), but the TBR was significantly higher in the 68Ga-FAPI-04 group compared with the 18F-FDG group (11.90 ± 8.35 vs. 3.14 ± 1.59, P &lt; 0.001). SUVmax and the TBR in 68Ga-FAPI-04 positive lesions were associated with tumour size (both P &lt; 0.05), but not the remaining clinical and pathological features (all P &gt; 0.05).Conclusions68Ga-FAPI-04 PET/CT is more sensitive than 18F-FDG PET/CT in detecting HCC lesions, and 68Ga-FAPI-04 uptake is correlated mainly with tumour size.
A New Prognostic Risk Signature of Eight Ferroptosis-Related Genes in the Clear Cell Renal Cell Carcinoma
Authors: Chen Ji , Zhan Yating , Zhang Rongrong , Chen Bo , Huang Junting , Li Chunxue , Zhang Wenjie , Wang Yajing , Gao Yuxiang , Zheng Jianjian , Li Yeping 
Published: June 2021

Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma and has poor prognosis in the locally advanced stage. Ferroptosis, a relatively new type of cell death, has gained significant attention in recent years. This study aimed to explore the prognostic value of ferroptosis-related genes (FRGs) in ccRCC. In this study, 50 differentially expressed FRGs between ccRCC and adjacent normal kidney tissues were identified, 26 of them correlated with overall survival (OS) (P &lt;0.05). Eight optimal FRGs were selected by Lasso regression and multivariate Cox regression analysis, and used to construct a new prognostic risk signature to predict the prognosis of ccRCC patients. In addition, the signature passed the validation of prognostic survival analyses by a significant margin, and the risk score was identified as an independent prognostic marker via Cox regression analyses. Further studies indicated that the signature was significantly correlated with immune cell infiltration. Moreover, the levels of eight FRGs were examined in ccRCC. Collectively, the 8-FRG prognostic risk signature helps the clinicians predict the prognosis and OS of the patients, and standardize prognostic assessments.
Identification of the Target for a Transition Metal-α-Amino Acid Complex Antibiotic Against Mycobacterium smegmatis
Authors: Karpin George W. , Merola Joseph S. , Falkinham Joseph O. 
Published: June 2021

Spontaneous mutants of Mycobacterium smegmatis strain mc2155 resistant to 1-PG (iridium-L-phenylglycine complex), an antimycobacterial antibiotic, were isolated. Based on the discovery that some 1-PG-resistant mutants (1-PGR) were also resistant to high concentrations of clarithromycin (≥250 μg/ml), but no other anti-mycobacterial antibiotics, the 23S rRNA region spanning the peptidyl transferase domain was sequenced and mutations shown to be localized in the peptidyl transferase domain of the 23S rRNA gene. Measurements showed that 1-PG bound to ribosomes isolated from the 1-PG-sensitive parental strain, but the ribosome binding values for the 1-PGR mutant reduced.
Mild Hypoxia Enhances the Expression of HIF and VEGF and Triggers the Response to Injury in Rat Kidneys
Authors: Xu Yaya , Kong Xiangmei , Li Jiru , Cui Tiantian , Wei Yifan , Xu Jiayue , Zhu Yueniu , Zhu Xiaodong 
Published: June 2021

BackgroundHypoxia contributes to a cascade of inflammatory response mechanisms in kidneys that result in the development of renal interstitial fibrosis and subsequent chronic renal failure. Nonetheless, the kidney possesses a self-protection mechanism under a certain degree of hypoxia and this mechanism its adaptation to hypoxia. As the hypoxia-inducible factor (HIF)–vascular endothelial growth factor (VEGF) axis is a key pathway for neovascularization, the activation of this axis is a target for renal hypoxia therapies.MethodsSprague–Dawley rats were exposed to normobaric hypoxia and subdivided into three groups, namely group A (21% O2), group B (10% O2), and group C (7% O2). Renal tissue samples were processed and analyzed to determine pathological morphological changes, the expression of HIF, VEGF, inflammation factor and vascular density.ResultsWe found that as the duration of hypoxia increased, destructive changes in the kidney tissues became more severe in group C (7% O2). In contrast, the increased duration of hypoxia did not exacerbate kidney damage in group B (10% O2). As the hypoxia was prolonged and the degree of hypoxia increased, the expression of HIF-1α increased gradually. As hypoxia time increased, the expression of VEGF increased gradually, but VEGF expression in group B (10% O2) was the highest. Group C (7% O2) had higher levels of IL-6, IL-10, and TNF-alpha. Additionally, the highest vascular density was observed in group B.ConclusionThese findings suggest that activating the HIF–VEGF signaling pathway to regulate angiogenesis after infliction of hypoxic kidney injury may provide clues for the development of novel CKD treatments.
Sleep Monitoring Using WatchPAT Device to Predict Recurrence of Major Depression in Patients at High Risk for Major Depression Disorder Recurrence: A Case Report
Authors: Harlev Daniel , Ravona-Springer Ramit , Nuriel Yonatan , Fruchter Eyal 
Published: June 2021

Background: Major depressive disorders are strongly correlated with alterations in sleep pattern and architecture, including changes in the Rapid Eye Movement (REM) phase. However, it is still unknown whether sleep alterations precede other depression-related symptoms, particularly in patients with recurrent depressive episodes at relapse risk.Case Presentation: We initiated a study aimed at examining the value of ambulatory sleep monitoring using a WatchPAT device, in predicting recurrence of Major depression. Depression was assessed monthly with the Beck Depression Inventory version II (BDI-II). Here we present the case of a 63 years old woman, with a history of recurrent depressive episodes. AT the time of recruitment, she was asymptomatic, she experienced recurrence of Major depression 3 months into the study. We observed a significant reduction of the Rem Latency parameters 5 weeks prior to BDI-II score increase, reflecting major depressive episode recurrence.Conclusion: Though our results are preliminary, they suggest that ambulatory sleep monitoring can be used as a simple and accessible tool, predicting recurrence of Major Depressive episodes in patients at high risk, thus enabling early treatment intervention.
Prevalence of Polypharmacy and Inappropriate Medication in Adults With Intellectual Disabilities in a Hospital Setting in Switzerland
Authors: Lonchampt Sophie , Gerber Fabienne , Aubry Jean-Michel , Desmeules Jules , Kosel Markus , Besson Marie 
Published: June 2021

Background: Polypharmacy and inappropriate prescription are frequent in vulnerable and multi-morbid populations. Adults with intellectual disability (ID) are at risk of being polymedicated because they often present with multiple comorbidities and challenging behaviors.Aim: The objective of this study was thus to evaluate the prevalence of potentially inappropriate medications (PIM) and polypharmacy in a hospital unit dedicated to adults with ID.Methods: A 10-month prospective observational study took place at a hospital unit specializing in the care of adults with ID in Geneva, Switzerland. Once a week, health and prescription data were collected and screened for PIM according to preset definitions.Results: Fourteen patients consented to participate, leading to 20 hospitalization events assessed during the study. Hospitalizations lasted 12.8 weeks on average. ID severities ranged from mild to profound, all degrees of severity being equally represented. One hundred percent of the patients were polymedicated (defined as five drugs or more prescribed simultaneously). A mean number of 9.4 drugs were prescribed per week, including 5.3 psychotropic drugs. The number of prescribed drugs remained stable throughout the hospitalizations. Antipsychotics were the most prescribed drug class (19% of all prescribed drugs), followed by benzodiazepines (13%) and laxatives (12%). A total of 114 PIM were recorded with an average of 5.7 PIM per hospitalization.Conclusions: This study showed that polypharmacy and inappropriate prescription are very common in adults with ID, even though the literature and expert positions advocate for deprescription in these patients. Specific prescribing and deprescribing guidelines are needed for that specific population.
Psychopathological Symptom Load and Distinguishable Cerebral Blood Flow Velocity Patterns in Patients With Schizophrenia and Healthy Controls: A Functional Transcranial Doppler Study
Authors: Egger Stephan T. , Bobes Julio , Rauen Katrin , Seifritz Erich , Vetter Stefan , Schuepbach Daniel 
Published: June 2021

Introduction: Schizophrenia is a severe psychiatric disorder, with executive dysfunction and impaired processing speed playing a pivotal role in the course of the disease. In patients with schizophrenia, neurocognitive deficits appear to be related to alterations in cerebral hemodynamics. It is not fully understood if psychopathological symptom load (i.e., presence and severity of symptoms) is also related to alterations in cerebral hemodynamics. We aim to study the relationship between psychopathological symptom load and cerebral hemodynamics in the Middle Cerebral Artery (MCA) during a cognitive task in patients with schizophrenia and healthy controls.Methodology: Cerebral hemodynamics in the MCA were examined in 30 patients with schizophrenia and 15 healthy controls using functional Transcranial Doppler (fTCD) during the Trail Making Test (TMT). Psychopathological symptoms were measured using the Brief Psychiatric Rating Scale (BPRS). Patients were dichotomized according to BPRS scores: mild-moderate (BPRS &lt; 41, n = 15) or marked-severe (BPRS ≧ 41, n = 15). Mean blood flow velocity (MFV) in the MCA and processing speed of the TMT were analyzed. Cerebral hemodynamics were analyzed using the general additional model (GAM) with a covariate analysis of variance (ANCOVA) for group comparisons.Results: Patients and healthy controls were comparable regarding demographics. Patients had a slower processing speed for the TMT-A (patients-severe: 52s, patients-moderate: 40s, healthy-controls: 32s, p = 0.019) and TMT-B [patients-severe: 111s, patients-moderate: 76s, healthy-controls: 66s, p &lt; 0.001)]. Patients demonstrated differing hemodynamic profiles in both TMTs: TMT- A [F(6, 1,792) = 17, p &lt; 0.000); TMT-B [F(6, 2,692) = 61.93, p &lt; 0.000], with a delay in increase in MFV and a failure to return to baseline values.Conclusions: Patients with schizophrenia demonstrated slower speeds of processing during both the TMT-A and TMT-B. The speed of processing deteriorated with increasing psychopathological symptom load, additionally a distinct cerebral hemodynamic pattern in the MCA was observed. Our results further support the view that severity of schizophrenia, particularly psychopathological symptom load, influences performance in neurocognitive tasks and is related to distinct patterns of brain hemodynamics.