bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transarterial Chemoembolization in Treatment-Naïve and Recurrent Hepatocellular Carcinoma: A Propensity-Matched Outcome and Risk Signature Analysis
Authors: Liu Yiming , Ren Yanqiao , Ge Sangluobu , Xiong Bin , Zhou Guofeng , Feng Gansheng , Song Songlin , Zheng Chuansheng 
Published: June 2021

ObjectivesThe purpose of this study was to evaluate the efficacy and safety of transarterial chemoembolization (TACE) in the treatment of patients with treatment-naïve hepatocellular carcinoma (TN-HCC) and recurrent HCC (R-HCC). In addition, risk signature analysis was performed to accurately assess patients’ recurrence and survival.MethodsThis retrospective study assessed the consecutive medical records of TN-HCC and R-HCC patients from January 2014 to December 2018. In order to reduce the patient selection bias, propensity score matching (PSM) analysis was applied. Conditional inference tree was used to establish a risk signature.ResultsA total of 401 eligible patients were included in our study, including 346 patients in the TN-HCC group and 55 patients in the R-HCC group. Forty-seven pairs of patients were chosen after the PSM analysis. Before the PSM analysis, the objective tumor regression (ORR) and disease control rate (DCR) of R-HCC patients were better than that of TN-HCC patients; however, after the PSM analysis, there was no significant difference in the ORR and DCR between the two groups (P&gt;0.05). Before the PSM analysis, the median overall survival (OS) and progression-free survival (PFS) in the R-HCC group were significantly greater than those of the TN-HCC group (OS: 24 months vs. 18 months, P =0.004; PFS: 9 months vs. 6 months, P =0.012). However, after the PSM analysis, the median OS and PFS in the R-HCC group were inferior to those in the TN-HCC group (OS: 24 months vs. 33 months, P= 0.0035; PFS: 10 months vs. 12 months, P = 0.01). The conditional inference tree divided patients into different subgroups according to tumor size, BCLC stage, and TACE sessions and shared different hazards ratio to recurrence or survival.ConclusionPatients with R-HCC treated with TACE achieved satisfactory results, although survival after the PSM analysis was not as good as in the TN-HCC group. In addition, risk signature based on conditional inference tree analysis can more accurately predict the recurrence and survival in both groups of patients.
Blood-Based Biomarkers for Glioma in the Context of Gliomagenesis: A Systematic Review
Authors: Ali Hamza , Harting Romée , de Vries Ralph , Ali Meedie , Wurdinger Thomas , Best Myron G. 
Published: June 2021

BackgroundGliomas are the most common and aggressive tumors of the central nervous system. A robust and widely used blood-based biomarker for glioma has not yet been identified. In recent years, a plethora of new research on blood-based biomarkers for glial tumors has been published. In this review, we question which molecules, including proteins, nucleic acids, circulating cells, and metabolomics, are most promising blood-based biomarkers for glioma diagnosis, prognosis, monitoring and other purposes, and align them to the seminal processes of cancer.MethodsThe Pubmed and Embase databases were systematically searched. Biomarkers were categorized in the identified biomolecules and biosources. Biomarker characteristics were assessed using the area under the curve (AUC), accuracy, sensitivity and/or specificity values and the degree of statistical significance among the assessed clinical groups was reported.Results7,919 references were identified: 3,596 in PubMed and 4,323 in Embase. Following screening of titles, abstracts and availability of full-text, 262 articles were included in the final systematic review. Panels of multiple biomarkers together consistently reached AUCs &gt;0.8 and accuracies &gt;80% for various purposes but especially for diagnostics. The accuracy of single biomarkers, consisting of only one measurement, was far more variable, but single microRNAs and proteins are generally more promising as compared to other biomarker types.ConclusionPanels of microRNAs and proteins are most promising biomarkers, while single biomarkers such as GFAP, IL-10 and individual miRNAs also hold promise. It is possible that panels are more accurate once these are involved in different, complementary cancer-related molecular pathways, because not all pathways may be dysregulated in cancer patients. As biomarkers seem to be increasingly dysregulated in patients with short survival, higher tumor grades and more pathological tumor types, it can be hypothesized that more pathways are dysregulated as the degree of malignancy of the glial tumor increases. Despite, none of the biomarkers found in the literature search seem to be currently ready for clinical implementation, and most of the studies report only preliminary application of the identified biomarkers. Hence, large-scale validation of currently identified and potential novel biomarkers to show clinical utility is warranted.
Prognostic Implication of a Novel Metabolism-Related Gene Signature in Hepatocellular Carcinoma
Authors: Yuan Chaoyan , Yuan Mengqin , Chen Mingqian , Ouyang Jinhua , Tan Wei , Dai Fangfang , Yang Dongyong , Liu Shiyi , Zheng Yajing , Zhou Chenliang , Cheng Yanxiang 
Published: June 2021

BackgroundHepatocellular carcinoma (HCC) is one of the main causes of cancer-associated deaths globally, accounts for 90% of primary liver cancers. However, further studies are needed to confirm the metabolism-related gene signature related to the prognosis of patients with HCC.MethodsUsing the “limma” R package and univariate Cox analysis, combined with LASSO regression analysis, a metabolism-related gene signature was established. The relationship between the gene signature and overall survival (OS) of HCC patients was analyzed. RT-qPCR was used to evaluate the expression of metabolism-related genes in clinical samples. GSEA and ssGSEA algorithms were used to evaluate differences in metabolism and immune status, respectively. Simultaneously, data downloaded from ICGC were used as an external verification set.ResultsFrom a total of 1,382 metabolism-related genes, a novel six-gene signature (G6PD, AKR1B15, HMMR, CSPG5, ELOVL3, FABP6) was constructed based on data from TCGA. Patients were divided into two risk groups based on risk scores calculated for these six genes. Survival analysis showed a significant correlation between high-risk patients and poor prognosis. ROC analysis demonstrated that the gene signature had good predictive capability, and the mRNA expression levels of the six genes were upregulated in HCC tissues than those in adjacent normal liver tissues. Independent prognosis analysis confirmed that the risk score and tumor grade were independent risk factors for HCC. Furthermore, a nomogram of the risk score combined with tumor stage was constructed. The calibration graph results demonstrated that the OS probability predicted by the nomogram had almost no deviation from the actual OS probability, especially for 3-year OS. Both the C-index and DCA curve indicated that the nomogram provides higher reliability than the tumor stage and risk scores. Moreover, the metabolic and immune infiltration statuses of the two risk groups were significantly different. In the high-risk group, the expression levels of immune checkpoints, TGF-β, and C-ECM genes, whose functions are related to immune escape and immunotherapy failure, were also upregulated.ConclusionsIn summary, we developed a novel metabolism-related gene signature to provide more powerful prognostic evaluation information with potential ability to predict the immunotherapy efficiency and guide early treatment for HCC.
Attitudes Toward and Use of Prostate-Specific Antigen Testing Among Urologists and General Practitioners in Germany: A Survey
Authors: Kappen Sanny , Jürgens Verena , Freitag Michael H. , Winter Alexander 
Published: June 2021

BackgroundIn 2020, around 1.4 million new prostate cancer (PCa) cases were recorded worldwide. Early detection of PCa by prostate-specific antigen (PSA) screening remains debated, leading to different specialist-specific recommendations in PCa guidelines. This study aimed to assess attitudes toward and use of PSA testing among urologists in Germany and general practitioners (GPs) in Lower Saxony (Germany).MethodsA nationwide questionnaire was sent to urologists via the mailing lists of the Professional Association of German Urologists and the German Urological Society. A version of the questionnaire for GPs was sent to email addresses via the Association of Statutory Health Insurance Physicians Lower Saxony. The online questionnaires covered use of PSA testing, information communication, handling of test results, and handling of/knowledge about national and international guidelines and recommendations on early detection of PCa. Statistical analysis was performed at a descriptive level.ResultsIn total, 432 of 6,568 urologists (6.6%) and 96 of 1,579 GPs (6.1%) participated in this survey. Urologists and GPs differed in their attitudes and approaches toward PSA testing. Most urologists (86.8%, n=375) judged the test as “very meaningful” or “meaningful”, compared with 52.1% (n=50) of GPs. Almost two-thirds of the urologists (64.4%, n=278) viewed the PCa mortality reduction by PSA testing as proven, compared with one-fifth of GPs (20.8%, n=20). Almost 80% of male urologists (79.9%, n=291) indicated that they would undergo a PSA test in the future (again), compared with 55.1% of male GPs (n=38). In addition, 56.3% (n=243) of urologists stated that “considerably more than half” or “almost all” men aged 45 years or older received a PSA test, compared with 19.8% (n=19) of GPs.ConclusionsUrologists are more convinced about the PSA test than GPs. PSA testing is therefore used more often in urological settings, although the preselected patient population must be considered. In accordance with specialist-specific recommendations, GPs show a more reserved approach toward PSA testing. Instead of focusing on different attitudes and recommendations on PSA testing, the exchange between specialist groups should be improved to achieve a consistent approach to PSA testing.
The Nonsteroidal Anti-Inflammatory Drug Ketorolac Alters the Small Intestinal Microbiota and Bile Acids Without Inducing Intestinal Damage or Delaying Peristalsis in the Rat
Authors: Hutka Barbara , Lázár Bernadette , Tóth András S. , Ágg Bence , László Szilvia B. , Makra Nóra , Ligeti Balázs , Scheich Bálint , Király Kornél , Al-Khrasani Mahmoud , Szabó Dóra , Ferdinandy Péter , Gyires Klára , Zádori Zoltán S. 
Published: June 2021

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) induce significant damage to the small intestine, which is accompanied by changes in intestinal bacteria (dysbiosis) and bile acids. However, it is still a question of debate whether besides mucosal inflammation also other factors, such as direct antibacterial effects or delayed peristalsis, contribute to NSAID-induced dysbiosis. Here we aimed to assess whether ketorolac, an NSAID lacking direct effects on gut bacteria, has any significant impact on intestinal microbiota and bile acids in the absence of mucosal inflammation. We also addressed the possibility that ketorolac-induced bacterial and bile acid alterations are due to a delay in gastrointestinal (GI) transit.Methods: Vehicle or ketorolac (1, 3 and 10 mg/kg) were given to rats by oral gavage once daily for four weeks, and the severity of mucosal inflammation was evaluated macroscopically, histologically, and by measuring the levels of inflammatory proteins and claudin-1 in the distal jejunal tissue. The luminal amount of bile acids was measured by liquid chromatography-tandem mass spectrometry, whereas the composition of microbiota by sequencing of bacterial 16S rRNA. GI transit was assessed by the charcoal meal method.Results: Ketorolac up to 3 mg/kg did not cause any signs of mucosal damage to the small intestine. However, 3 mg/kg of ketorolac induced dysbiosis, which was characterized by a loss of families belonging to Firmicutes (Paenibacillaceae, Clostridiales Family XIII, Christensenellaceae) and bloom of Enterobacteriaceae. Ketorolac also changed the composition of small intestinal bile by decreasing the concentration of conjugated bile acids and by increasing the amount of hyodeoxycholic acid (HDCA). The level of conjugated bile acids correlated negatively with the abundance of Erysipelotrichaceae, Ruminococcaceae, Clostridiaceae 1, Muribaculaceae, Bacteroidaceae, Burkholderiaceae and Bifidobacteriaceae. Ketorolac, under the present experimental conditions, did not change the GI transit.Conclusion: This is the first demonstration that low-dose ketorolac disturbed the delicate balance between small intestinal bacteria and bile acids, despite having no significant effect on intestinal mucosal integrity and peristalsis. Other, yet unidentified, factors may contribute to ketorolac-induced dysbiosis and bile dysmetabolism.
PK11195 Protects From Cell Death Only When Applied During Reperfusion: Succinate-Mediated Mechanism of Action
Authors: Seidlmayer Lea K. , Hanson Benjamin J. , Thai Phung N. , Schaefer Saul , Bers Donald M. , Dedkova Elena N. 
Published: June 2021

Aim: Reperfusion after myocardial ischemia causes cellular injury, in part due to changes in mitochondrial Ca2+ handling, oxidative stress, and myocyte energetics. We have previously shown that the 18-kDa translocator protein of the outer mitochondrial membrane (TSPO) can modulate Ca2+ handling. Here, we aim to evaluate the role of the TSPO in ischemia/reperfusion (I/R) injury.Methods: Rabbit ventricular myocytes underwent simulated acute ischemia (20 min) and reperfusion (at 15 min, 1 h, and 3 h) in the absence and presence of 50 μM PK11195, a TSPO inhibitor. Cell death was measured by lactate dehydrogenase (LDH) assay, while changes in mitochondrial Ca2+, membrane potential (ΔΨm), and reactive oxygen species (ROS) generation were monitored using confocal microscopy in combination with fluorescent indicators. Substrate utilization was measured with Biolog mitochondrial plates.Results: Cell death was increased by ~200% following I/R compared to control untreated ventricular myocytes. Incubation with 50 μM PK11195 during both ischemia and reperfusion did not reduce cell death but increased mitochondrial Ca2+ uptake and ROS generation. However, application of 50 μM PK11195 only at the onset and during reperfusion effectively protected against cell death. The large-scale oscillations in ΔΨm observed after ~1 h of reperfusion were significantly delayed by 1 μM cyclosporin A and almost completely prevented by 50 μM PK11195 applied during 3 h of reperfusion. After an initial increase, mitochondrial Ca2+, measured with Myticam, rapidly declined during 3 h of reperfusion after the initial transient increase. This decline was prevented by application of PK11195 at the onset and during reperfusion. PK11195 prevented a significant increase in succinate utilization following I/R and succinate-induced forward-mode ROS generation. Treatment with PK11195 was also associated with a significant increase in glutamate and a decrease in leucine utilization.Conclusion: PK11195 administered specifically at the moment of reperfusion limited ROS-induced ROS release and cell death, likely in part, by a shift from succinate to glutamate utilization. These data demonstrate a unique mechanism to limit cardiac injury after I/R.
Assessment of the Effect of Recruitment Maneuver on Lung Aeration Through Imaging Analysis in Invasively Ventilated Patients: A Systematic Review
Authors: Pierrakos Charalampos , Smit Marry R. , Hagens Laura A. , Heijnen Nanon F. L. , Hollmann Markus W. , Schultz Marcus J. , Paulus Frederique , Bos Lieuwe D. J. 
Published: June 2021

Background: Recruitment maneuvers (RMs) have heterogeneous effects on lung aeration and have adverse side effects. We aimed to identify morphological, anatomical, and functional imaging characteristics that might be used to predict the RMs on lung aeration in invasively ventilated patients.Methods: We performed a systemic review. Studies included invasively ventilated patients who received an RM and in whom re-aeration was examined with chest computed tomography (CT), electrical impedance tomography (EIT), and lung ultrasound (LUS) were included.Results: Twenty studies were identified. Different types of RMs were applied. The amount of re-aerated lung tissue after an RM was highly variable between patients in all studies, irrespective of the used imaging technique and the type of patients (ARDS or non-ARDS). Imaging findings suggesting a non-focal morphology (i.e., radiologic findings consistent with attenuations with diffuse or patchy loss of aeration) were associated with higher likelihood of recruitment and lower chance of overdistention than a focal morphology (i.e., radiological findings suggestive of lobar or segmental loss of aeration). This was independent of the used imaging technique but only observed in patients with ARDS. In patients without ARDS, the results were inconclusive.Conclusions: ARDS patients with imaging findings suggestive of non-focal morphology show most re-aeration of previously consolidated lung tissue after RMs. The role of imaging techniques in predicting the effect of RMs on re-aeration in patients without ARDS remains uncertain.
The Sexual Development, Sexual Health, Sexual Experiences, and Sexual Knowledge of Forensic Mental Health Patients: A Research Design and Methodology Protocol
Authors: Brand Elnike , Ratsch Angela , Heffernan Edward 
Published: June 2021

Introduction: There is substantial evidence that severe mental illness (SMI) can have significant impacts on general development, knowledge acquisition, and quality of life including sexual function. However, whilst the sexual development, sexual health, sexual experiences and sexual knowledge of the broader Australian community and the Australian prisoner population have been well-described, these concepts have been less explored in people with a SMI. In particular, there is an absence of research around these topics involving people who are subject to a treatment order (aka a Forensic Order) under the relevant jurisdictional Mental Health Act.Methods and Analysis: People currently under the treatment requirements of a Queensland Forensic Order will be invited to participate in this descriptive, mixed-method study. The study will be conducted in three phases. The first two phases will involve 50 participants (100 face-to-face quantitative interviews) with the aim of mapping sexual development, sexual health, sexual experiences, and sexual knowledge. The third phase will involve qualitative semi-structured interviews with a purposely enrolled, informant-rich cohort identified through the quantitative surveys until saturation is reached. Quantitative data will be analyzed using descriptive and comparative statistics. Qualitative data will be analyzed by content analysis of the major themes.Ethics and dissemination: The project has ethics approval from a Queensland Health Human Research Ethics Committee. Results will be reported to participants and other stakeholders at seminars and conferences and through peer-reviewed publications.Strengths and Limitations of this Study: This is a mixed-method study which engages with participants by using face-to-face interviews. The study is conducted in three phases which sub-divide the research into the following areas: (1) demographics, general health, and sexual health, (2) sexual knowledge and experiences, and (3) sexual knowledge gaps. This study uses electronic data capture to efficiently record and analyse participant responses. This study captures self-reported data and uses non-probability sampling from a population who have been pre-selected through an arms-length approach—both these processes elevate the risk of bias.
Sustainable Laboratory Capacity Building After the 2014 Ebola Outbreak in the Republic of Guinea
Authors: Ndjomou Jean , Shearrer Scott , Karlstrand Brendan , Asbun Carmen , Coble Jesse , Alam Jane S. , Mar Mar P. , Presser Lance , Poynter Scott , Michelotti Julia M. , Wauquier Nadia , Ross Casey , Altmann Sharon 
Published: June 2021

Background: The 2014–2016 West Africa Ebola virus disease outbreak heavily impacted the Republics of Guinea, Sierra Leone, and Liberia. The outbreak uncovered the weaknesses of the public health systems, including inadequately trained and insufficient health personnel as well as limited and poorly equipped health infrastructures. These weaknesses represent significant threats to global health security. In the wake of the outbreak, affected countries made urgent requests for international engagement to help strengthening the public health systems.Methods: This work describes the successful multi-year implementation of a laboratory capacity building program in the Republic of Guinea. The program integrated biorisk and quality management systems training, infectious diseases diagnostic training, facility engineering and maintenance training, and mentorship to strengthen Guinea's bio-surveillance capacity.Results: The major outcome of these efforts was an established and local staff-operated public health laboratory that performs disease surveillance and reporting and diagnostic of priority diseases and pathogens of security concerns.Conclusions: This work has improved the Guinea country's capabilities to address country public health issues and preparedness to respond to future infectious disease threats.
Effect of Aging Vessel (Clay-Tinaja versus Oak Barrel) on the Volatile Composition, Descriptive Sensory Profile, and Consumer Acceptance of Red Wine
Authors: Issa-Issa Hanán , Lipan Leontina , Cano-Lamadrid Marina , Nemś Agnieszka , Corell Mireia , Calatayud-García Pablo , Carbonell-Barrachina Ángel A. , López-Lluch David 
Published: June 2021

Consumers look for unique wines, offering pleasant experiences. Wine producers need to open new markets and are targeting countries with fewer traditions in drinking red and complex wines, such as Poland, Russia and Germany. The use of less popular aging vessels (e.g., clay-tinajas) will help in creating unique wines. The aim of this study was to evaluate the effect of the aging vessel on the volatile and sensory profiles and consumer acceptance of red wine in Spain and Poland (model of potential new markets). Three wines were studied: (i) wine A, aged in a clay-tinaja with non-permeable coating); (ii) wine B, aged in clay-tinaja without coating; and (iii) wine C, aged in oak barrels (control). The key families in the volatile profiles were esters (wines B and C) and organic acids and terpenes (wine A). Wine A was described as sour and bitter, wine B had a distinctive mineral note, and wine C had a complex profile with typical wood notes. Finally, wines C and A were the preferred ones for Spanish and Polish consumers, respectively. Clay-tinaja wine A can be a good option to introduce clay-tinaja wines in Polish and similar markets because it is a unique product and fulfills the sensory demands/habits of Polish consumers.