bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal Analysis of Circulating Tumor Cells in Colorectal Cancer Patients by a Cytological and Molecular Approach: Feasibility and Clinical Application
Authors: Hendricks Alexander , Dall Katharina , Brandt Burkhard , Geisen Reinhild , Röder Christian , Schafmayer Clemens , Becker Thomas , Hinz Sebastian , Sebens Susanne 
Published: June 2021

IntroductionLiquid biopsies allowing for individualized risk stratification of cancer patients have become of high significance in individualized cancer diagnostics and treatment. The detection of circulating tumor cells (CTC) has proven to be highly relevant in risk prediction, e.g., in colorectal cancer (CRC) patients. In this study, we investigate the clinical relevance of longitudinal CTC detection over a course of follow-up after surgical resection of the tumor and correlate these findings with clinico-pathological characteristics.MethodsIn total, 49 patients with histologically proven colorectal carcinoma were recruited for this prospective study. Blood samples were analyzed for CTC presence by two methods: first by marker-dependent immunofluorescence staining combined with automated microscopy with the NYONE® cell imager and additionally, indirectly, by semi-quantitative Cytokeratin-20 (CK20) RT-qPCR. CTC quantification data were compared and correlated with the clinico-pathological parameters.ResultsDetection of CTC over a post-operative time course was feasible with both applied methods. In patients who were pre-operatively negative for CTCs with the NYONE® method or below the cut-off for relative CK20 mRNA expression after analysis by PCR, a statistically significant rise in the immediate post-operative CTC detection could be demonstrated. Further, in the cohort analyzed by PCR, we detected a lower CTC load in patients who were adjuvantly treated with chemotherapy compared to patients in the follow-up subgroup. This finding was contrary to the same patient subset analyzed with the NYONE® for CTC detection.ConclusionOur study investigates the occurrence of CTC in CRC patients after surgical resection of the primary tumor and during postoperative follow-up. The resection of the tumor has an impact on the CTC quantity and the longitudinal CTC analysis supports the significance of CTC as a prognostic biomarker. Future investigations with an even more extended follow-up period and larger patient cohorts will have to validate our results and may help to define an optimal longitudinal sampling scheme for liquid biopsies in the post-operative monitoring of cancer patients to enable tailored therapy concepts for precision medicine.
Molecular Markers of MDR of Chemotherapy for HSCC: Proteomic Screening With High-Throughput Liquid Chromatography-Tandem Mass Spectrometry
Authors: Shen Bin , Dong Xuelin , Yuan Bo , Zhang Zhijun 
Published: June 2021

BackgroundHypopharyngeal squamous cell cancer (HSCC) is a head and neck tumor with a poor prognosis. Chemotherapy lacks effectiveness because of multidrug resistance (MDR), which has increased toxic side effects. Thus, there is an urgent need to identify the molecular markers of MDR of chemotherapy for HSCC.MethodsFifty clinical samples of HSCC were derived from patients including 12 sensitive or resistant to chemotherapy drugs. Proteomic screening was performed using liquid chromatography-tandem mass spectrometry (LC-MS), which was based on data-independent acquisition. Molecular markers of MDR of chemotherapy in patients with HSCC were identified with clinical data and validated with ELISA.ResultsA total of 673 differentially expressed proteins were identified in HSCC samples, where 172 were upregulated and 501 were downregulated. A total of 183 differentially expressed proteins including 102 upregulated and 81 downregulated proteins, were identified by comparing cancer sensitive to chemotherapy with cancer resistant to chemotherapy. Clinical HSCC samples had significantly higher expression of FADD and significantly lower expression of RIPK1. Expressions of FADD and RIPK1 proteins were significantly lower in the chemotherapy-sensitive group. These expression differences were not correlated with clinical data. RIPK1 and FADD are involved in necroptosis and the signaling pathway of PRRs. Using ELISA, the low expression of RIPK1 and FADD was found in the patients sensitive to chemotherapy.ConclusionLC-MS proteomics is an effective method to identify the molecular markers of HSCC. FADD and RIPK1 can act as molecular markers of MDR of chemotherapy in patients with HSCC and may function through necroptosis and the PRR signaling pathway.
Relationship Between Ultrasound Features and Ki-67 Labeling Index of Soft Tissue Sarcoma
Authors: Wang Pingping , Li Hai , Hu Yu , Peng Xiaojing , Ye Xinhua , Xu Di , Li Ao 
Published: June 2021

ObjectivesTo explore the relationship between ultrasound (US) features and Ki-67 labeling index (LI) of soft tissue sarcoma (STS).MethodsForty-six patients with 47 STS lesions, between September 2014 and April 2020, were enrolled in the study. Point-biserial correlation analysis and Spearman’s correlation analysis were utilized to examining the relationship between the US features and the Ki-67 LI of STS. The differences of US features between high and low Ki-67 proliferation groups were statistically analyzed by independent t test, Wilcoxon rank-sum test, and Fisher’s exact test. The optimal cut-off points of US features revealing significant differences were estimated by the maximum Youden index.ResultsA moderate correlation between the vascular density grade and the Ki-67 LI (ρ = 0.409, P = 0.004) was found in this study. In addition, other ultrasound features were irrelevant to the Ki-67 LI. The cut-off for differentiating low- and high-proliferation groups was grade II according to the best Youden index. The area under receiver operating characteristic (ROC) curve was 0.74 (p = 0.011) with a sensitivity of 60.6% and specificity of 78.6%.ConclusionsOnly the vascular density grade of STS had a weak positive correlation with Ki-67 LI, and might be capable of predicting the proliferation of STS. Other ultrasonographic features of STS such as shape and tumor margin have no correlation with Ki-67 LI.
Case Report: Treatment of Alectinib in NSCLC With Brain Metastasis Patient Refractory to Radiotherapy After Resistance to Crizotinib
Authors: Zhang Chunzhi 
Published: June 2021

BackgroundBrain metastasis is the most common form of tumor recurrence after resistance to crizotinib in patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC). The treatment of brain metastasis in patients with ALK-positive NSCLC requires a multidisciplinary approach, including targeted therapy, chemotherapy, and radiotherapy. At present, no optimal treatment for these patients has been identified, although radiotherapy has remained a vital treatment.Case PresentationWe experienced a patient with ALK-positive NSCLC who developed brain metastasis after crizotinib therapy. ALK rearrangement was not detected in a blood sample using next-generation sequencing. In accordance with National Comprehensive Cancer Network guidance, the patient underwent whole-brain radiotherapy. However, the number of metastatic sites unexpectedly increased. In desperation, the patient was empirically given alectinib after radiotherapy failure, and unanticipated success was achieved.ConclusionsThis case revealed some new insights. First, liquid biopsy is complementary to tissue biopsy in patients with NSCLC, mainly in those with EGFR mutation. However, ALK rearrangement should be assessed using tissue biopsy as much as possible. Second, brain metastasis of NSCLC might respond to second-generation tyrosine kinase inhibitors (TKIs), such as alectinib and ceritinib, after resistance to crizotinib regardless of the presence or absence of ALK rearrangement in liquid biopsy. Finally, combined radiotherapy and TKI therapy appears optimal in patients with brain metastasis of NSCLC after resistance to crizotinib in the absence of a definitive driver gene.
Castaneroxy A From the Leaves of Castanea sativa Inhibits Virulence in Staphylococcus aureus
Authors: Salam Akram M. , Porras Gina , Cho Young-Saeng K. , Brown Morgan M. , Risener Caitlin J. , Marquez Lewis , Lyles James T. , Bacsa John , Horswill Alexander R. , Quave Cassandra L. 
Published: June 2021

Methicillin-resistant Staphylococcus aureus (MRSA) represents one of the most serious infectious disease concerns worldwide, with the CDC labeling it a “serious threat” in 2019. The current arsenal of antibiotics works by targeting bacterial growth and survival, which exerts great selective pressure for the development of resistance. The development of novel anti-infectives that inhibit quorum sensing and thus virulence in MRSA has been recurrently proposed as a promising therapeutic approach. In a follow-up of a study examining the MRSA quorum sensing inhibitory activity of extracts of Italian plants used in local traditional medicine, 224C-F2 was reported as a bioactive fraction of a Castanea sativa (European chestnut) leaf extract. The fraction demonstrated high activity in vitro and effective attenuation of MRSA pathogenicity in a mouse model of skin infection. Through further bioassay-guided fractionation using reverse-phase high performance liquid chromatography, a novel hydroperoxy cycloartane triterpenoid, castaneroxy A (1), was isolated. Its structure was established by nuclear magnetic resonance, mass spectrometry and X-ray diffraction analyses. Isomers of 1 were also detected in an adjacent fraction. In a series of assays assessing inhibition of markers of MRSA virulence, 1 exerted activities in the low micromolar range. It inhibited agr::P3 activation (IC50 = 31.72 µM), δ-toxin production (IC50 = 31.72 µM in NRS385), supernatant cytotoxicity to HaCaT human keratinocytes (IC50 = 7.93 µM in NRS385), and rabbit erythrocyte hemolytic activity (IC50 = 7.93 µM in LAC). Compound 1 did not inhibit biofilm production, and at high concentrations it exerted cytotoxicity against human keratinocytes greater than that of 224C-F2. Finally, 1 reduced dermonecrosis in a murine model of MRSA infection. The results establish 1 as a promising antivirulence candidate for development against MRSA.
Cannabidiol and Sertraline Regulate Behavioral and Brain Gene Expression Alterations in an Animal Model of PTSD
Authors: Gasparyan Ani , Navarrete Francisco , Manzanares Jorge 
Published: June 2021

This study evaluated the effects of cannabidiol (CBD) and/or sertraline (STR) on behavioral and gene expression alterations induced by a new chronic animal model of post-traumatic stress disorder (PTSD). C57BL/6J male mice were repeatedly exposed to physical and psychogenic alternate stressful stimuli. Fear-related memory and anxiety-like behaviors were evaluated. The effects of the administration of CBD (20 mg/kg, i.p.) and/or STR (10 mg/kg, p.o.) were analyzed on behavioral and gene expression changes induced by the model of PTSD. Gene expression alterations of targets related with stress regulation, endocannabinoid and serotonergic systems were analyzed by real-time PCR. The results revealed an increased and long-lasting fear-related memory and anxiety-like behaviors in mice exposed to the animal model of PTSD. Treatment with CBD improved these behaviors in PTSD animals, effects that were significantly potentiated when combined with STR. Gene expression analyses revealed a long-term increase of corticotropin releasing factor (Crf) that was significantly normalized with the combination CBD plus STR. Cannabinoid receptors (Cnr1 and Cnr2) were up regulated in PTSD mice whereas the serotonin transporter (Slc6a4) was reduced. Interestingly, CBD and STR alone or combined induced a significant and marked increase of Slc6a4 gene expression. These results point out the cooperative action of the combination CBD plus STR to enhance fear extinction and reduce anxiety-like behaviors, normalizing gene expression alterations in this animal model of PTSD and suggesting that the combination of CBD with STR deserves to be further explored for the treatment of patients with PTSD.
Quantitative Proteomics Reveal That Metabolic Improvement Contributes to the Cardioprotective Effect of T89 on Isoproterenol-Induced Cardiac Injury
Authors: Wei Xiao-Hong , Guo Xiao , Pan Chun-Shui , Li Huan , Cui Yuan-Chen , Yan Li , Fan Jing-Yu , Deng Jing-Na , Hu Bai-He , Chang Xin , He Shu-Ya , Yan Lu-Lu , Sun Kai , Wang Chuan-She , Han Jing-Yan 
Published: June 2021

BackgroundT89, a traditional Chinese medicine, has passed phase II, and is undergoing phase III clinical trials for treatment of ischemic cardiovascular disease by the US FDA. However, the role of T89 on isoproterenol (ISO)-induced cardiac injury is unknown. The present study aimed to explore the effect and underlying mechanism of T89 on ISO-induced cardiac injury.MethodsMale Sprague-Dawley rats received subcutaneous injection of ISO saline solution at 24 h intervals for the first 3 days and then at 48 h intervals for the next 12 days. T89 at dose of 111.6 and 167.4 mg/kg was administrated by gavage for 15 consecutive days. Rat survival rate, cardiac function evaluation, morphological observation, quantitative proteomics, and Western blotting analysis were performed.ResultsT89 obviously improved ISO-induced low survival rate, attenuated ISO-evoked cardiac injury, as evidenced by myocardial blood flow, heart function, and morphology. Quantitative proteomics revealed that the cardioprotective effect of T89 relied on the regulation of metabolic pathways, including glycolipid metabolism and energy metabolism. T89 inhibited the enhancement of glycolysis, promoted fatty acid oxidation, and restored mitochondrial oxidative phosphorylation by regulating Eno1, Mcee, Bdh1, Ces1c, Apoc2, Decr1, Acaa2, Cbr4, ND2, Cox 6a, Cox17, ATP5g, and ATP5j, thus alleviated oxidative stress and energy metabolism disorder and ameliorated cardiac injury after ISO. The present study also verified that T89 significantly restrained ISO-induced increase of HSP70/HSP40 and suppressed the phosphorylation of ERK, further restored the expression of CX43, confirming the protective role of T89 in cardiac hypertrophy. Proteomics data are available via ProteomeXchange with identifier PXD024641.ConclusionT89 reduced mortality and improves outcome in the model of ISO-induced cardiac injury and the cardioprotective role of T89 is correlated with the regulation of glycolipid metabolism, recovery of mitochondrial function, and improvement of myocardial energy.
Association Between Obsessive-Compulsive Symptom Dimensions in Mothers and Psychopathology in Their Children
Authors: Blanco-Vieira Thiago , Hoexter Marcelo Queiroz , Batistuzzo Marcelo C. , Alvarenga Pedro , Szejko Natalia , Fumo Afonso Mazine Tiago , Miguel Eurípedes C. , do Rosário Maria Conceição 
Published: June 2021

Background:The non-clinical presentation of obsessive–compulsive symptoms (OCS) in women may impact not only their daily lives and well-being but also increase the risk for emotional and behavioral problems in their children. This study aims to investigate the OCS dimension distribution in a large sample of mothers from a cohort of school age children and the association between these OCS dimensions with their own psychopathology, and with the presence of OCS and other psychopathology in their children.Method:Our final sample consisted of 2,511 mother-children dyads recruited from the elementary schools of two large cities. Throughout multiple regression analysis, we examined the correlations between demographic and clinical variables of mothers assessed by the Mini International Psychiatric Interview (MINI) and the Dimensional Yale-Brown Obsessive-Compulsive Scale-Short Version (DY-BOCS-SV) with children's psychopathology status reported by the Child Behavior Checklist (CBCL).Results:The overall prevalence of mothers who reported experiencing at least one OCS was 40% (N= 1,004). “Aggression/violence” was the most frequent symptom dimension (32.2%), followed by the “symmetry/ordering” (16.4%) and the “sexual/religious” dimensions (13.8%). There was a significant correlation between the presence of OCS and maternal psychopathology in general (p&lt; 0.001,r= 0.397). Not only the presence but also the severity of the mother's OCS were strongly correlated to the total (p&lt; 0.001), internalizing (p&lt; 0.001), externalizing (p&lt; 0.001), and OCS subscale scores (p&lt; 0.001) on the CBCL.Conclusion:OCS dimensions are highly prevalent in women. Presence and severity of maternal OCS are related to children's psychopathology and behavioral problems.
Identification of Gene Loci That Overlap Between Mental Disorders and Poor Prognosis of Cancers
Authors: Xu Ji-li , Guo Yong 
Published: June 2021

Background: Co-morbid psychiatric disorders are common in patients with cancers, which make the treatment more difficult. Studying the connection between mental disease-related genes and the prognosis of cancers may potentially lead to novel therapeutic methods.Method: All mental disorders genes were selected from published articles. The correlations between the expression of these genes and the prognosis of different cancers were analyzed by starBase v2.0 and TIMER. The molecular functions, reactome pathways, and interactions among diverse genes were explored via the STRING tool.Results: 239 genes were identified for further survival analysis, 5 of which were overlapping genes across at least five cancer types, including RHEBL1, PDE4B, ANKRD55, EPHB2, and GIMAP7. 146 high-expression and 157 low-expression genes were found to be correlated with the unfavorable prognosis of diverse cancer types. Tight links existed among various mental disease genes. Besides, risk genes were mostly related to the dismal outcome of low-grade glioma (LGG) and kidney renal clear cell carcinoma (KIRC) patients. Gene Ontology (GO) and reactome pathway analysis revealed that most genes involved in various critical molecular functions and primarily related to metabolism, signal transduction, and hemostasis.Conclusions: To explore co-expression genes between mental illnesses and cancers may aid in finding preventive strategies and therapeutic methods for high-risk populations and patients with one or more diseases.
SARs for the Antiparasitic Plant Metabolite Pulchrol. 3. Combinations of New Substituents in A/B-Rings and A/C-Rings
Authors: Terrazas Paola , Salamanca Efrain , Dávila Marcelo , Manner Sophie , Gimenez Alberto , Sterner Olov 
Published: June 2021

The natural products pulchrol and pulchral, isolated from the roots of the Mexican plant Bourreria pulchra, have previously been shown to possess antiparasitic activity towards Trypanosoma cruzi, Leishmania braziliensis and L. amazonensis, which are protozoa responsible for Chagas disease and leishmaniasis. These infections have been classified as neglected diseases, and still require the development of safer and more efficient alternatives to their current treatments. Recent SARs studies, based on the pulchrol scaffold, showed which effects exchanges of its substituents have on the antileishmanial and antitrypanosomal activity. Many of the analogues prepared were shown to be more potent than pulchrol and the current drugs used to treat leishmaniasis and Chagas disease (miltefosine and benznidazole, respectively), in vitro. Moreover, indications of some of the possible interactions that may take place in the binding sites were also identified. In this study, 12 analogues with modifications at two or three different positions in two of the three rings were prepared by synthetic and semi-synthetic procedures. The molecules were assayed in vitro towards T. cruzi epimastigotes, L. braziliensis promastigotes, and L. amazonensis promastigotes. Some compounds had higher antiparasitic activity than the parental compound pulchrol, and in some cases even benznidazole and miltefosine. The best combinations in this subset are with carbonyl functionalities in the A-ring and isopropyl groups in the C-ring, as well as with alkyl substituents in both the A- and C-rings combined with a hydroxyl group in position 1 (C-ring). The latter corresponds to cannabinol, which indeed was shown to be potent towards all the parasites.
Analisis Dampak Platform Peer-To-Peer Airbnb Terhadap Usaha Perhotelan Konvensional di Provinsi Bali
Authors: Ganapati I Dewa Gede , Sukwika Tatan , Sulistyadi Yohanes 
Published: June 2021

The sharing economy platforms in the accommodation, such as Airbnb, gain more public attention. Several hoteliers in Indonesia have complained about the unequal playing of the field due to the alleged tax violations. Some studies on the impact of Airbnb have been discussed in various countries, but this subject has not been widely conducted in Indonesia. This study aims to determine the impact of Airbnb on the conventional hotel industry in Bali and how the conventional hotel’s response to compete with Airbnb. This research was conducted using qualitative research. Data was collected through interviews and secondary data collection. Interviews were conducted with representatives of hoteliers, Airbnb owners, and hospitality associations in Bali. Using forecasting analysis, this study finds that the presence of Airbnb in Bali has an impact on the occupancy rate of conventional hotels in Bali. However, there doesn't a significant impact from Airbnb regarding the hospitality revenue. Meanwhile, conventional hoteliers generally do not make particular efforts to compete with Airbnb. This research implies for the managerial side of hotels and public programs and policies, especially for the Government of Bali in the future to pay attention to consumer protection to provide equal action between conventional hotel and Airbnb owners.
Factor structure of the complex preparedness of young football players 12-13 years old
Authors: Cieślicka M. , Muszkieta R. , Bejtka M. , Gryn I. 
Published: June 2021

Purpose: to determine the factor structure of the complex readiness of young football players 12-13 years old based on the level of development of physical qualities, mastery of technical elements and indicators of psychophysiological functions. Material and methods. Participants: 48 football players 12-13 years old participated in the study of the sports club “Kolos”, Kharkiv, Ukraine. All children started to play football in the age of 10-11, that is, the duration of football classes was 1-2 years. Research methods. The following data were determined: indicators of the level of physical preparedness, indicators of the level of technical preparedness, indicators of the psychophysiological functional state. The structure of complex preparedness was determined using factor analysis (SPSS-17, Dimension Redaction - Factor; Extraction Method: Principal Component Analysis; Varimax with Kaiser Normalization). Results. In the structure of complex training of young football players aged 12-13, 4 main factors were identified: 1 - "Speed-power and technical training" (30.36% of the total dispersion); 2 - "Attention switching" (20.7% of the total variance); 3 - "Sensitivity of the nervous system" (15.4% of the total dispersion); 4 - "Mobility of the nervous system" (13.9% of the total dispersion). Conclusions. Speed and strength, technical training in combination with switching of attention and mobility of the nervous system are dominated in the structure of complex training of young football players aged 12-13. The obtained data create conditions for recommendations in the training process of young football players aged 12-13 increase the number of exercises that require the development of speed and strength, technical training in combination with exercises to switch attention.