bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Therapies for Parkinsonian Syndromes–Recent Progress and Future Perspectives
Authors: Przewodowska Dominika , Marzec Weronika , Madetko Natalia 
Published: August 2021

Background: Atypical parkinsonian syndromes are rare, fatal neurodegenerative diseases associated with abnormal protein accumulation in the brain. Examples of these syndromes include progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration. A common clinical feature in parkinsonism is a limited improvement with levodopa. So far, there are no disease-modifying treatments to address these conditions, and therapy is only limited to the alleviation of symptoms. Diagnosis is devastating for patients, as prognosis is extremely poor, and the disease tends to progress rapidly. Currently, potential causes and neuropathological mechanisms involved in these diseases are being widely investigated.Objectives: The goal of this review is to summarize recent advances and gather emerging disease-modifying therapies that could slow the progression of atypical parkinsonian syndromes.Methods: PubMed and Google Scholar databases were searched regarding novel perspectives for atypical parkinsonism treatment. The following medical subject headings were used: “atypical parkinsonian syndromes—therapy,” “treatment of atypical parkinsonian syndromes,” “atypical parkinsonian syndromes—clinical trial,” “therapy of tauopathy,” “alpha-synucleinopathy treatment,” “PSP therapy/treatment,” “CBD therapy/treatment,” “MSA therapy/treatment,” and “atypical parkinsonian syndromes—disease modifying.” All search results were manually reviewed prior to inclusion in this review.Results: Neuroinflammation, mitochondrial dysfunction, microglia activation, proteasomal impairment, and oxidative stress play a role in the neurodegenerative process. Ongoing studies and clinical trials target these components in order to suppress toxic protein accumulation. Various approaches such as stem cell therapy, anti-aggregation/anti-phosphorylation agent administration, or usage of active and passive immunization appear to have promising results.Conclusion: Presently, disease-modifying strategies for atypical parkinsonian syndromes are being actively explored, with encouraging preliminary results. This leads to an assumption that developing accurate, safe, and progression-halting treatment is not far off. Nevertheless, the further investigation remains necessary.
Development of a Prognostic Scoring System for Hepatocellular Carcinoma Patients With Main Portal Vein Tumor Thrombus Undergoing Conventional Transarterial Chemoembolization: An Analysis of 173 Patients
Authors: Li Jing-huan , Yin Xin , Fan Wen-shuai , Zhang Lan , Chen Rong-xin , Chen Yi , Li Li-xin , Ge Ning-ling , Gan Yu-hong , Wang Yan-hong , Ren Zheng-gang 
Published: August 2021

BackgroundPatients with hepatocellular carcinoma (HCC) with main portal vein tumor thrombus (mPVTT) have poor prognosis. Promising systemic therapies, such as target therapies, have limited benefits. The purpose of this study is to retrospectively evaluate the benefits of conventional TACE (c-TACE) and to establish a prognostic stratification of HCC patients with mPVTT.MethodsThis is a single center retrospective study conducted over 5 years (duration of performing c-TACE), on consecutive HCC patients with mPVTT receiving c-TACE. Univariable and multivariable analysis were used to explore factors independently associated with overall survival (OS). Based on Cox-regression analysis, prognostic models were developed and internally validated by bootstrap methods. Discrimination and performance were measured by Akaike information criterion, concordance index, and likelihood ratio test.ResultsA total of 173 patients were included. Median OS was 6.0 months (95%CI: 3.92~8.08). The independent variables correlated with survival were largest tumor diameter, tumor number, mPVTT extension, and AFP. In the final model, patients were assigned 2 points if largest tumor diameter ≥8 cm, or tumor number ≥2, 1point if main trunk was complete obstructed, or AFP ≥400 ng/ml. By summing up these points, patients were divided into three risk groups according to the score at the 15rd and 85th percentiles, in which median OS were 18, 7, and 3.5months, respectively (p&lt;0.001). The model shown optimal discrimination, performance, and calibration.Conclusionsc-TACE could provide survival benefits in HCC patients with mPVTT and the proposed prognostic stratification may help to identify good candidates for the treatment, and those for whom c-TACE may be futile.
CEUS-Based Radiomics Can Show Changes in Protein Levels in Liver Metastases After Incomplete Thermal Ablation
Authors: Bao Haiwei , Chen Ting , Zhu Junyan , Xie Haiyang , Chen Fen 
Published: August 2021

ObjectiveTo investigate the ability of contrast-enhanced ultrasound (CEUS)-based radiomics combined with machine learning to detect early protein changes after incomplete thermal ablation.MethodsHCT-26 colorectal adenoma cells were engrafted into the livers of 80 mice, which were randomly divided into 4 groups for palliative laser ablation. Changes in heat shock protein (HSP) and apoptosis-related protein expression in the tumors were assessed. SCID mice subjected to CEUS and ultrasonography were divided into training (n=56) and test (n=24) datasets. Then, 102 features from seven feature groups were extracted. We use the least absolute shrinkage and selection operator (LASSO) feature selection method to fit the machine learning classifiers. The feature selection methods and four classifiers were combined to determine the best prediction model.ResultsThe areas under the receiver-operating characteristic curves (AUCs) of the classifiers in the test dataset ranged from 0.450 to 0.932 (median: 0.721). The best score was obtained from the model in which the omics data of CEUS was analyzed in the arterial phase by random forest (RF) classification.ConclusionsA machine learning model, in which radiomics characteristics are extracted by multimodal ultrasonography, can accurately, rapidly and noninvasively identify protein changes after ablation.
Successful Treatment of Refractory and Relapsed CNS Acute Lymphoblastic Leukemia With CD-19 CAR-T Immunotherapy: A Case Report
Authors: Htun Kyaw Thu , Gong Qiang , Ma Le , Wang Ping , Tan Ya , Wu Guangsheng , Chen Jieping 
Published: August 2021

In recent decades, survival was significantly improved in B cell acute lymphoblastic leukemia (B-ALL) patients. But refractory and relapsed B-ALL still has aggressive clinical behavior and poor prognosis. Especially, the patients with central nervous system infiltration is very difficult to achieve complete remissions with routine treatment. Chimeric antigen receptor-modified T-cell therapy targeting CD-19 has shown to be a beneficial treatment approach in refractory and relapsed B cell acute lymphoblastic leukemia (r/r ALL). However, there are very few studies reporting to treatment of refractory and relapsed B cell ALL with central nervous system infiltration. Here, we reported one single case of a patient diagnosed with relapsed B cell ALL with CNS infiltration who was successfully treated by second generation CAR containing a co-stimulator CD28 or 4-1BB therapy. Long-term proliferation of CAR-T cells in peripheral blood and bone marrow was observed more than 18 months. After CAR-T treatment, the patient got toxicity of grade 1 cytokine release syndrome and achieved significantly 36 months event free survival of follow-up. It is suggested that CD-19 CAR containing CD28 or 4-1BB costimulatory may be an effective therapy in refractory and relapsed B cell ALL with central nervous system infiltration. Its toxicity is mild, and its safety is high.Clinical Trial Registration:ClinicalTrials.gov Identifier: NCT02349698.
Transferrin-Conjugated Erianin-Loaded Liposomes Suppress the Growth of Liver Cancer by Modulating Oxidative Stress
Authors: Yang Anhui , Sun Zhen , Liu Rui , Liu Xin , Zhang Yue , Zhou Yulin , Qiu Ye , Zhang Xinrui 
Published: August 2021

BackgroundLiver cancer is one of the most malignant human cancers, with few treatments and a poor prognosis. Erianin (ERN) is a natural compound with multiple pharmacological activities that has been reported to have numerous excellent effects against liver cancer in experimental systems. However, its application in vivo has been limited due to its poor aqueous solubility and numerous off-target effects. This study aimed to improve the therapeutic efficacy of ERN by developing novel ERN-loaded tumor-targeting nanoparticles.ResultsIn this study, ERN was loaded into liposomes by ethanol injection (LP-ERN), and the resulting LP-ERN nanoparticles were treated with transferrin to form Tf-LP-ERN to improve the solubility and enhance the tumor-targeting of ERN. LP-ERN and Tf-LP-ERN nanoparticles had smooth surfaces and a uniform particle size, with particle diameters of 62.60 nm and 88.63 nm, respectively. In HepG2 and SMMC-7721 cells, Tf-LP-ERN induced apoptosis, decreased mitochondrial membrane potentials and increased ERN uptake more effectively than free ERN and LP-ERN. In xenotransplanted mice, Tf-LP-ERN inhibited tumor growth, but had a minimal effect on body weight and organ morphology. In addition, Tf-LP-ERN nanoparticles targeted tumors more effectively than free ERN and LP-ERN nanoparticles, and in tumor tissues Tf-LP-ERN nanoparticles promoted the cleavage PARP-1, caspase-3 and caspase-9, increased the expression levels of Bax, Bad, PUMA, and reduced the expression level of Bcl-2. Moreover, in the spleen of heterotopic tumor model BALB/c mice, ERN, LP-ERN and Tf-LP-ERN nanoparticles increased the expression levels of Nrf2, HO-1, SOD-1 and SOD-2, but reduced the expression levels of P-IKKα+β and P-NF-κB, with Tf-LP-ERN nanoparticles being most effective in this regard. Tf-LP-ERN nanoparticles also regulated the expression levels of TNF-α, IL-10 and CCL11 in serum.ConclusionTf-LP-ERN nanoparticles exhibited excellent anti-liver cancer activity in vivo and in vitro by inducing cellular apoptosis, exhibiting immunoregulatory actions, and targeting tumor tissues, and did so more effectively than free ERN and LP-ERN nanoparticles. These results suggest that the clinical utility of a Tf-conjugated LP ERN-delivery system for the treatment of liver cancer warrants exploration.
Transcriptomic and Proteomic Study on the High-Fat Diet Combined With AOM/DSS-Induced Adenomatous Polyps in Mice
Authors: Guo Cui , Xu Yimin , Han Xinyue , Liu Xiaoqiang , Xie Runnan , Cheng Zhihong , Fu Xiaoling 
Published: August 2021

ObjectiveTo screen and identify molecular targets and bacteria genus leading to adenomatous polyps in mouse induced by high-fat diet (HFD) +AOM/DSS using omics technology.MethodsThe molecular targets of colorectal adenoma disease were obtained from the GeneCards and OMIM database. The SPF C57BL mice were randomly divided into blank (Control) and AOM/DSS+HFD colorectal adenoma model (ADH) groups. The ADH model group was intraperitoneally injected with AOM reagent. Then, mice were given with 2.5% DSS (in free drinking water) and high-fat diet to establish the mouse model. During this period, the changes of physical signs of mice in each group were observed. After the end of modeling, HE staining was used to evaluate the histopathological change of mice. The differentially expressed genes and proteins in the Control group and ADH group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. The histological results were analyzed by intersection with the intestinal adenoma molecular targets obtained from the database. Moreover, the changes of intestinal flora in the two groups were examined. The correlation between targets and differential bacteria was analyzed and verified by Parallel Reaction Monitoring (PRM) to comprehensively evaluate the mouse model of adenomatous polyp induced by AOM/DSS+HFD.ResultsThe general condition and histopathological results of mice confirmed that the ADH mouse model was successfully established and tubular adenoma was formed. A total of 604 genes and 42 proteins related to intestinal adenoma were obtained by histological analysis and database intersection analysis. The intestinal microflora of ADH mice was different from that of normal mice, and the constituents and abundance of intestinal flora were similar to those of human intestinal adenoma. GATA4 and LHPP were selected as potential pathological markers of the model mice by correlation analysis of targets and intestinal flora. The results of PRM verification were highly consistent with the results of RNA-Seq transcriptome sequencing and TMT analysis.ConclusionThe pathological results, molecular pathological markers and the changes of intestinal flora suggest that the mouse ADH model is ideal for studying the transformation of inflammatory cancer. The ADH model will be helpful for understanding the occurrence and development of human colorectal cancer at the transcriptomic and proteomic level.
Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei of Appendiceal Origin: A Single Center Experience
Authors: Santullo Francesco , Pacelli Fabio , Abatini Carlo , Attalla El Halabieh Miriam , Fortunato Giusy , Lodoli Claudio , Giovinazzo Francesco , Rotolo Stefano , Di Giorgio Andrea 
Published: August 2021

Background: Pseudomyxoma peritonei (PMP) originating from appendiceal mucinous neoplasm is a rare peritoneal malignancy characterized by the progressive intraperitoneal accumulation of mucus leading to death if left untreated. In recent years, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) offered increased survival rates. This study aims to identify the clinical, pathological, and surgical features influencing safety and survival outcomes of patients undergoing CRS and HIPEC for PMP of appendiceal origin.Methods: A retrospective analysis of all patients undergoing CRS and HIPEC for PMP of appendiceal origin from January 2015 to May 2019 was conducted at our institution.Results: Study population included 50 patients (74% female, 26% male). The median age at CRS was 60 (38–84). The median peritoneal cancer index (PCI) was 17. Complete cytoreductive surgery (CC 0–1) was achieved in 47 patients (94%). HIPEC chemotherapeutic regimen was based on oxaliplatin for 13 (28%) patients and mitomycin for 34 (72%) patients. We experienced a total of 19 (38%) postoperative complications, of which 14 (74%) of grade I-II and 5 (26%) of grade III-IV, according to the Clavien-Dindo classification. The median follow-up period was 27 months (12–107) from the date of cytoreductive surgery. The mean survival rate was 100 months, with a 5-year OS of 91%. The mean progression-free survival rate was 77 months (0–107), with a 5-year PFS of 63%. Multivariate analysis identified adenocarcinoma histotype and incomplete cytoreduction to significantly worsen progression-free survival, while incomplete cytoreduction was the only independent predictor of poorer overall survival.Conclusion: Complete cytoreduction and appendiceal neoplasm histotype play a crucial role in the survival of patients affected by PMP of appendiceal origin. The rates of morbidity associated with CRS and HIPEC for PMP are acceptable.
Implementing emergency admission risk prediction in general practice: a qualitative study
Authors: Evans Bridie Angela , Dale Jeremy , Davies Jan , Hutchings Hayley , Kingston Mark , Porter Alison , Russell Ian , Williams Victoria , Snooks Helen 
Published: August 2021

BackgroundUsing computer software in general practice to predict patient risk of emergency hospital admission has been widely advocated, despite limited evidence about effects. In a trial evaluating the introduction of a Predictive Risk Stratification Model (PRISM), statistically significant increases in emergency hospital admissions and use of other NHS services were reported without evidence of benefits to patients or the NHS.AimTo explore GPs’ and practice managers’ experiences of incorporating PRISM into routine practice.Design and settingSemi-structured interviews were carried out with GPs and practice managers in 18 practices in rural, urban, and suburban areas of south Wales.MethodInterviews (30–90 min) were conducted at 3–6 months after gaining PRISM access, and ∼18 months later. Data were analysed thematically using Normalisation Process Theory.ResultsResponders (n = 22) reported that the decision to use PRISM was based mainly on fulfilling Quality and Outcomes Framework incentives. Most applied it to <0.5% practice patients over a few weeks. Using PRISM entailed undertaking technical tasks, sharing information in practice meetings, and making small-scale changes to patient care. Use was inhibited by the model not being integrated with practice systems. Most participants doubted any large-scale impact, but did cite examples of the impact on individual patient care and reported increased awareness of patients at high risk of emergency admission to hospital.ConclusionQualitative results suggest mixed views of predictive risk stratification in general practice and raised awareness of highest-risk patients potentially affecting rates of unplanned hospital attendance and admissions. To inform future policy, decision makers need more information about implementation and effects of emergency admission risk stratification tools in primary and community settings.
Floral design GaN crystals: low-resistive and low-dislocation-density growth by oxide vapor phase epitaxy
Authors: Takino Junichi , Sumi Tomoaki , Okayama Yoshio , Kitamoto Akira , Usami Shigeyoshi , Imanishi Masayuki , Yoshimura Masashi , Mori Yusuke 
Published: August 2021

Abstract
GaN crystal growth mode in the oxide vapor phase epitaxy (OVPE) method, which simultaneously provides low electrical resistance and low threading dislocation density (TDD), has been investigated in detail. The results clarified that these qualities can be achieved by the expression of numerous inverted pyramidal pits, called three-dimensional (3D) growth mode. This mode reduced TDD from 3.8 × 106 cm−2 to 2.0 × 104 cm−2 for 1 mm thick growth because the threading dislocations (TDs) converged to the center of each pit. Moreover, when the crystal surface after polishing was observed by photoluminescence measurement, peculiar floral designs reflecting the distribution of oxygen concentration were observed over the entire surface. In addition, the etch pits exhibited TDs in the center of each floral design. On the basis of our results, we proposed that the 3D-OVPE-GaN will serve as a key material for improving the performance of vertical GaN devices.
Escópica de videos confesionales en Youtube ¿Lugares de resistencia o Subjetividades en suspensión?
Authors: Rodríguez Cuberos Édgar Giovanni 
Published: August 2021

El texto indaga, en clave exploratoria, la atención a las dimensiones ésteticas desplegadas en el consumo de videos confesionales como parte de la relación de niños y jóvenes como usuarios de la Internet. Se problematiza la ausencia de los maestros y la escuela en la interpelación de dichos productos de consumo y sus impactos en las subjetividades, dando como resultado lo que se denomina aquí subjetividades en suspensión, es decir, cuerpos y mentes predispuestos a la captura, al pensamiento de medianía en su devenir propiamente tele/ maquínico. Se proponen algunos modos probables de resistencia.
Sobre la diversidad sexual en la escuela
Authors: Castelar C. Andrés Felipe 
Published: August 2021

El texto presenta un acercamiento a la diversidad sexual y de género desde una perspectiva “Queer”, con el fin de reconocer su lugar en el cambio cultural que se le exige a la escuela hoy. La fórmula sexo-género es vista como un sistema clasificatorio que puede ser desafiado en vez de asumirlo como real y normativo para la educación. Al desnaturalizar las producciones del lenguaje, dadas como verdades, y poner en tensión las desigualdades propias de la Modernidad, se espera que la diversidad opere como estrategia de convivencia.
Territorios nómadas: nuevos lenguajes y subjetividades. Una experiencia sobre el lenguaje juvenil e infantil en la escuela
Authors: Delgado Ríos Zulma Giovanna , Morales Carrillo Luis Carlos , Rodríguez Rodríguez Nelson Custodio 
Published: August 2021

La escuela contemporánea es un reflejo de los constantes flujos de cambio en las dinámicas sociales, los cuales la han coaccionado en un lugar del desarraigo, de sujetos sin sentido de pertenencia e identidad hacia el lugar que habitan. Sin embargo, dicho contexto es el interés del proyecto Territorios nómadas como una reflexión permanente en el aula sobre aquel espacio significante. Integra los diferentes modos de expresión y el liderazgo de propuestas didácticas que fortalecen el reconocimiento de seres con decisión y participación política, autonomía, valores críticos y propositivos frente a las hacendosas situaciones que hoy enfrenta la sociedad colombiana.
La escuela como territorio de prácticas de resistencia en escenarios de emergencia social, Toribío-Cauca: “El que es Nasa resiste
Authors: Hernández Castillo Camila Andrea , Cetina Ramos Nury Marcela , García Donato Pablo Ariel 
Published: August 2021

El presente artículo muestra los resultados de la investigación “Prácticas de resistencia en escenarios de emergencia social: comunidad Nasa, Toribío-Cauca”, desarrollada en el marco de una investigación cualitativa e inscrita en un enfoque hermenéutico, que utilizó la Cartografía Social y entrevistas a profundidad como herramientas para la recolección de información, lo cual permitió identificar el papel de la escuela en las prácticas de resistencia generadas por la comunidad Nasa, de Toribío-Cauca, frente a las relaciones de poder que se producen en escenarios de emergencia social.
Genealogía de la maestra de preescolar en la escuela distrital de Bogotá (1980-1990)
Authors: Cárdenas Forero Oscar Leonardo 
Published: August 2021

El presente artículo de investigación, desde un enfoque cualitativo, describe las condiciones que permitieron la emergencia y existencia de la maestra de preescolar en la escuela oficial de Bogotá; la investigación se ubica en la década de los 80, momento en el que convergieron diversos acontecimientos discursivos y no discursivos que, acoplados, favorecieron su instalación. Se pretende reconocerle un lugar diferente a la maestra de preescolar, develando sus actuaciones y participación en el nuevo modo de ser de la escuela pública del país.