bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scoring System Based on RNA Modification Writer-Related Genes to Predict Overall Survival and Therapeutic Response in Bladder Cancer
Authors: Zhang Pu , Liu Zijian , Wang Decai , Li Yunxue , Xing Yifei , Xiao Yajun 
Published: August 2021

IntroductionIt’s widely reported the “writer” enzymes mediated RNA adenosine modifications which is known as a crucial mechanism of epigenetic regulation in development of tumor and the immunologic response in many kinds of cancers. However, the potential roles of these writer genes in the progression of bladder cancer (BLCA) remain unclear.Materials and MethodsWe comprehensively described the alterations of 26 RNA modification writer genes in BLCA from the genetic and transcriptional fields and identified writer-related genes from four independent datasets. Utilizing least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression, we constructed a ten writer-related gene signature. After that, we confirmed the predictive and prognostic value of this signature on another six independent datasets and established a nomogram to forecast the overall survival (OS) and mortality odds of BLCA patients clinically.ResultsThe writer-related genes signature showed good performance in predicting the OS for BLCA patients. Moreover, the writer-related gene signature was related to EMT-related pathways and immune characteristics. Furthermore, the immune cell infiltration levels of CD8 T cells, cytotoxic cells, M1/2 macrophage cells and tumor mutation burden might be able to predict which patients will benefit from immunotherapy. This could also be reflected by the writer-related gene signature.ConclusionsThis signature might play an important role in precision individualized immunotherapy. The present work highlights the crucial clinical implications of RNA modifications and may help developing individualized therapeutic strategies for patients with BLCA.
Potential Role of NEU1 in Hepatocellular Carcinoma: A Study Based on Comprehensive Bioinformatical Analysis
Authors: Wu Zhulin , He Li , Yang Lina , Fang Xuehong , Peng Lisheng 
Published: August 2021

Background: Aberrant expression of NEU1 has been identified in many malignancies. Nevertheless, the clinical significance of NEU1 in hepatocellular carcinoma (HCC) has not been fully elucidated.Methods: In our study, multiple databases, including ONCOMINE, The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC), Cancer Cell Line Encyclopedia (CCLE), Human Protein Atlas (HPA), Kaplan-Meier (KM) plotter, MethSurv, Gene Expression Profiling Interactive Analysis (GEPIA), and Metascape, etc., were utilized to investigate the expression, prognostic value, and function of NEU1 in HCC.Results: ONCOMINE, GEO, and TCGA analyses revealed that NEU1 was more highly expressed in HCC compared to normal tissues. Additionally, the mRNA and protein expression levels of NEU1 were increased in liver cancer cell lines and HCC tissues, respectively. Moreover, a trend toward increased NEU1 expression with advanced stage or grade was found. Furthermore, higher mRNA expression of NEU1 was found to be remarkably correlated with worse survival in HCC patients, and multivariate Cox analysis indicated that high mRNA expression of NEU1 was an independent prognostic factor for poor prognosis of HCC patients. Also, 21 methylated CpGs were found to be significantly related to HCC prognosis. Besides, functional enrichment analyses indicated that high NEU1 expression group had lower levels of B cells, CD8+ T cells, NK cells, and T helper cells, etc. than the low NEU1 expression group, and NEU1 may regulate a variety of tumor-related proteins and pathways, including lysosome, spliceosome, mTOR signaling pathway and so on.Conclusion: High expression level of NEU1 was positively correlated with unfavorable prognosis of HCC patients, which may be related to the regulation of cancer-associated pathways and the inhibition of immune function by NEU1. Thus, NEU1 could be used as a potential prognostic biomarker and target for HCC.
Prediction of Cognitive Decline Using Heart Rate Fragmentation Analysis: The Multi-Ethnic Study of Atherosclerosis
Authors: Costa Madalena D. , Redline Susan , Hughes Timothy M. , Heckbert Susan R. , Goldberger Ary L. 
Published: August 2021

Background: Heart rate fragmentation (HRF), a new non-invasive metric quantifying cardiac neuroautonomic function, is associated with increasing age and cardiovascular disease. Since these are risk factors for cognitive decline and dementia, in the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated whether disrupted cardiac neuroautonomic function, evidenced by increased HRF, would be associated with worse cognitive function assessed concurrently and at a later examination, and with greater cognitive decline.Methods: HRF was derived from the ECG channel of the polysomnographic recordings obtained in an ancillary study (n = 1,897) conducted in conjunction with MESA exam 5 (2010–2012). Cognitive function was assessed at exam 5 and 6.4 ± 0.5 years later at exam 6 (2016–2018) with tests of global cognitive performance (the Cognitive Abilities Screening Instrument, CASI), processing speed (Digit Symbol Coding, DSC) and working memory (Digit Span). Multivariable regression models were used to quantify the associations between HRF indices and cognitive scores.Results: The participants’ mean age was 68 ± 9 years (54% female). Higher HRF at baseline was independently associated with lower cognitive scores at both exams 5 and 6. Specifically, in cross-sectional analyses, a one-standard deviation (SD) (13.7%) increase in HRF was associated with a 0.51 (95% CI: 0.17–0.86) points reduction in CASI and a 1.12 (0.34–1.90) points reduction in DSC. Quantitatively similar effects were obtained in longitudinal analyses. A one-SD increase in HRF was associated with a 0.44 (0.03–0.86) and a 1.04 (0.28–1.81) points reduction in CASI and DSC from exams 5 to 6, respectively. HRF added predictive value to the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE-APOE-ε4) risk score and to models adjusted for serum concentration of NT-proBNP, an analyte associated with cognitive impairment and dementia.Conclusion: Increased HRF assessed during sleep was independently associated with diminished cognitive performance (concurrent and future) and with greater cognitive decline. These findings lend support to the links between cardiac neuroautonomic regulation and cognitive function. As a non-invasive, repeatable and inexpensive probe, HRF technology may be useful in monitoring cognitive status, predicting risk of dementia and assessing therapeutic interventions.
Reduced Hippocampal GABA+ Is Associated With Poorer Episodic Memory in Healthy Older Women: A Pilot Study
Authors: Jiménez-Balado Joan , Ycaza Herrera Alexandra , Igwe Kay , Klem Lynda , Buyukturkoglu Korhan , Irimia Andrei , Chen Liu , Guo Jia , Brickman Adam M. , Eich Teal S. 
Published: August 2021

Background: The current pilot study was designed to examine the association between hippocampal γ-aminobutyric acid (GABA) concentration and episodic memory in older individuals, as well as the impact of two major risk factors for Alzheimer’s disease (AD)—female sex and Apolipoprotein ε4 (ApoE ε4) genotype—on this relationship.Methods: Twenty healthy, community-dwelling individuals aged 50–71 (11 women) took part in the study. Episodic memory was evaluated using a Directed Forgetting task, and GABA+ was measured in the right hippocampus using a Mescher-Garwood point-resolved magnetic resonance spectroscopy (MRS) sequence. Multiple linear regression models were used to quantify the relationship between episodic memory, GABA+, ApoE ɛ4, and sex, controlling for age and education.Results: While GABA+ did not interact with ApoE ɛ4 carrier status to influence episodic memory (p = 0.757), the relationship between GABA+ and episodic memory was moderated by sex: lower GABA+ predicted worse memory in women such that, for each standard deviation decrease in GABA+ concentration, memory scores were reduced by 11% (p = 0.001).Conclusions: This pilot study suggests that sex, but not ApoE ɛ4 genotype, moderates the relationship between hippocampal GABA+ and episodic memory, such that women with lower GABA+ concentration show worse memory performance. These findings, which must be interpreted with caution given the small sample size, may serve as a starting point for larger studies using multimodal neuroimaging to understand the contributions of GABA metabolism to age-related memory decline.
Zytux in Refractory Myasthenia Gravis: A Multicenter, Open-Labeled, Clinical Trial Study of Effectiveness and Safety of a Rituximab Biosimilar
Authors: Fatehi Farzad , Moradi Kamyar , Okhovat Ali Asghar , Shojatalab Ghazaleh , Sedighi Behnaz , Boostani Reza , Sarraf Payam , Haghi Ashtiani Bahram , Ghasemi Majid , Moussavi Soussan , Anjidani Nassim , Nafissi Shahriar 
Published: August 2021

Objectives: Myasthenia gravis (MG) is an immune-mediated neuromuscular disorder responsive to immunomodulatory treatments. 10–20% of MGs are not responsive to conventional first-line therapies. Here, we sought to investigate the efficacy and safety of rituximab therapy in the treatment of patients with refractory MG.Methods: In a 48-week, multicenter, open-labeled, prospective cohort setting, 34 participants with refractory MG were assigned to receive infusions of Zytux, which is a rituximab biosimilar, according to a validated protocol. Clinical, functional, and quality of life (QoL) measurements were recorded at baseline, and seven further visits using the Myasthenia Gravis Foundation of America (MGFA), Myasthenia Gravis Composite (MGC), Myasthenia Gravis Activities of Daily Living profile (MG-ADL), and Myasthenia Gravis Quality of Life (MGQoL-15) scales. Besides, the post-infusion side effects were systematically assessed throughout the study.Results: The correlation analysis performed by generalized estimating equations analysis represented a significant reduction of MGC, MG-ADL, and MGQoL-15 scores across the trial period. The subgroup analysis based on the patients' clinical status indicated a significant effect for the interaction between time and MGFA subtypes on MG-ADL score, MGC score, and pyridostigmine prednisolone dose, reflecting that the worse clinical condition was associated with a better response to rituximab. Finally, no serious adverse event was documented.Conclusions: Rituximab therapy could improve clinical, functional, and QoL in patients with refractory MG in a safe setting. Further investigations with larger sample size and a more extended follow-up period are warranted to confirm this finding.Clinical Trial Registration: The study was registered by the Iranian Registry of Clinical Trials (IRCT) (Code No: IRCT20150303021315N18).
Pre- and Interhospital Workflow Times for Patients With Large Vessel Occlusion Stroke Transferred for Endovasvular Thrombectomy
Authors: van Meenen Laura C. C. , Riedijk Frank , Stolp Jeffrey , van der Veen Bas , Halkes Patricia H. A. , van der Ree Taco C. , Majoie Charles B. L. M. , Roos Yvo B. W. E. M. , Smeekes Martin D. , Coutinho Jonathan M. 
Published: August 2021

Background: Patients with large vessel occlusion (LVO) stroke are often initially admitted to a primary stroke center (PSC) and subsequently transferred to a comprehensive stroke center (CSC) for endovascular thrombectomy (EVT). This interhospital transfer delays initiation of EVT. To identify potential workflow improvements, we analyzed pre- and interhospital time metrics for patients with LVO stroke who were transferred from a PSC for EVT.Methods: We used data from the regional emergency medical services and our EVT registry. We included patients with LVO stroke who were transferred from three nearby PSCs for EVT (2014–2021). The time interval between first alarm and arrival at the CSC (call-to-CSC time) and other time metrics were calculated. We analyzed associations between various clinical and workflow-related factors and call-to-CSC time, using multivariable linear regression.Results: We included 198 patients with LVO stroke. Mean age was 70 years (±14.9), median baseline NIHSS was 14 (IQR: 9–18), 136/198 (69%) were treated with intravenous thrombolysis, and 135/198 (68%) underwent EVT. Median call-to-CSC time was 162 min (IQR: 137–190). In 133/155 (86%) cases, the ambulance for transfer to the CSC was dispatched with the highest level of urgency. This was associated with shorter call-to-CSC time (adjusted β [95% CI]: −27.6 min [−51.2 to −3.9]). No clinical characteristics were associated with call-to-CSC time.Conclusion: In patients transferred from a PSC for EVT, median call-to-CSC time was over 2.5 h. The highest level of urgency for dispatch of ambulances for EVT transfers should be used, as this clearly decreases time to treatment.
Pulmonary Toxicity After Total Body Irradiation – Critical Review of the Literature and Recommendations for Toxicity Reporting
Authors: Vogel Jennifer , Hui Susanta , Hua Chia-Ho , Dusenbery Kathryn , Rassiah Premavarthy , Kalapurakal John , Constine Louis , Esiashvili Natia 
Published: August 2021

IntroductionTotal body irradiation is an effective conditioning regimen for allogeneic stem cell transplantation in pediatric and adult patients with high risk or relapsed/refractory leukemia. The most common adverse effect is pulmonary toxicity including idiopathic pneumonia syndrome (IPS). As centers adopt more advanced treatment planning techniques for TBI, total marrow irradiation (TMI), or total marrow and lymphoid irradiation (TMLI) there is a greater need to understand treatment-related risks for IPS for patients treated with conventional TBI. However, definitions of IPS as well as risk factors for IPS remain poorly characterized. In this study, we perform a critical review to further evaluate the literature describing pulmonary outcomes after TBI.Materials and MethodsA search of publications from 1960-2020 was undertaken in PubMed, Embase, and Cochrane Library. Search terms included “total body irradiation”, “whole body radiation”, “radiation pneumonias”, “interstitial pneumonia”, and “bone marrow transplantation”. Demographic and treatment-related data was abstracted and evidence quality supporting risk factors for pulmonary toxicity was evaluated.ResultsOf an initial 119,686 publications, 118 met inclusion criteria. Forty-six (39%) studies included a definition for pulmonary toxicity. A grading scale was provided in 20 studies (17%). In 42% of studies the lungs were shielded to a set mean dose of 800cGy. Fourteen (12%) reported toxicity outcomes by patient age. Reported pulmonary toxicity ranged from 0-71% of patients treated with TBI, and IPS ranged from 1-60%. The most common risk factors for IPS were receipt of a TBI containing regimen, increasing dose rate, and lack of pulmonary shielding. Four studies found an increasing risk of pulmonary toxicity with increasing age.ConclusionsDefinitions of IPS as well as demographic and treatment-related risk factors remain poorly characterized in the literature. We recommend routine adoption of the diagnostic workup and the definition of IPS proposed by the American Thoracic Society. Additional study is required to determine differences in clinical and treatment-related risk between pediatric and adult patients. Further study using 3D treatment planning is warranted to enhance dosimetric precision and correlation of dose volume histograms with toxicities.
Kratom Use Within the Context of the Evolving Opioid Crisis and the COVID-19 Pandemic in the United States
Authors: Prozialeck Walter C. , Lamar Peter C. , Krupp Michael , Moon Matthew , Phelps Laura E. , Grundmann Oliver 
Published: August 2021

Kratom (Mitragyna speciosa, Korth.) is an evergreen tree that is indigenous to Southeast Asia. When ingested, kratom leaves or decoctions from the leaves have been reported to produce complex stimulant and opioid-like effects. For generations, native populations in Southeast Asia have used kratom products to stave off fatigue, improve mood, alleviate pain and manage symptoms of opioid withdrawal. Despite the long history of kratom use in Asia, it is only within the past 10–20 years that kratom has emerged as an important herbal agent in the United States, where it is being used for the self-treatment of pain, opioid withdrawal symptoms, and mood disorders. The increase in the use of kratom in the United States has coincided with the serious epidemic of opioid abuse and dependence. Since 2015, efforts to restrict access to prescription opioids have resulted in a marked increase in the use of “street” opioids such as heroin and illicit fentanyl. At the same time, many patients with chronic pain conditions or opioid use disorder have been denied access to appropriate medical help. The lack of access to care for patients with chronic pain and opioid use disorder has been magnified by the emergence of the COVID-19 pandemic. In this report, we highlight how these converging factors have led to a surge in interest in kratom as a potential harm reduction agent in the treatment of pain and opioid use disorder.
Global Surgery Indicators and Pediatric Hydrocephalus: A Multicenter Cross-Country Comparative Study Building the Case for Health System Strengthening
Authors: Ferraris Kevin Paul , Palabyab Eric Paolo M. , Kim Sergei , Matsumura Hideaki , Yap Maria Eufemia C. , Cloma-Rosales Venus Oliva , Letyagin German , Muroi Ai , Baticulon Ronnie E. , Alcazaren Jose Carlos , Seng Kenny , Navarro Joseph Erroll 
Published: August 2021

Objective: The aim of this study is to compare specific three-institution, cross-country data that are relevant to the Global Surgery indicators and the functioning of health systems.Methods: We retrospectively reviewed the clinical and socioeconomic characteristics of pediatric patients who underwent cerebrospinal fluid (CSF) diversion surgery for hydrocephalus in three different centers: the University of Tsukuba Hospital in Ibaraki, Japan (HIC), the Jose R. Reyes Memorial Medical Center in Manila, Philippines [low-to-middle-income country (LMIC)], and the Federal Neurosurgical Center in Novosibirsk, Russia (UMIC). The outcomes of interest were the timing of CSF diversion surgery and mortality. Statistical tests included descriptive statistics, Cox proportional hazards model, and logistic regression. Nation-level data were also obtained to provide the relevant socioeconomic contexts in discussing the results.Results: In total, 159 children were included, where 13 are from Japan, 99 are from the Philippines, and 47 are from the Russian Federation. The median time to surgery at the specific neurosurgical centers was 6 days in the Philippines and 1 day in both Japan and Russia. For the cohort from the Philippines, non-poor patients were more likely to receive CSF diversion surgery at an earlier time (HR = 4.74, 95% CI 2.34–9.61, p &lt;0.001). In the same center, those with infantile or posthemorrhagic hydrocephalus (HR = 3.72, 95% CI 1.70–8.15, p = 0.001) were more likely to receive CSF diversion earlier compared to those with congenital hydrocephalus, and those with postinfectious (HR = 0.39, 95% CI 0.22–0.70, p = 0.002) or myelomeningocele-associated hydrocephalus (HR = 0.46, 95% CI 0.22–0.95, p = 0.037) were less likely to undergo surgery at an earlier time. For Russia, older patients were more likely to receive or require early CSF diversion (HR = 1.07, 95% CI 1.01–1.14, p = 0.035). External ventricular drain (EVD) insertion was found to be associated with mortality (cOR 14.45, 95% CI 1.28–162.97, p = 0.031).Conclusion: In this study, Filipino children underwent late time-interval of CSF diversion surgery and had mortality differences compared to their Japanese and Russian counterparts. These disparities may reflect on the functioning of the health systems of respective countries.
Civil war in Ukraine. Content, development, actors
Authors: Ланской Г.Н. 
Published: August 2021

Статья посвящена событиям Гражданской войны на Украине в период между 1918 и 1920 годами. На уровнях практической деятельности и идеологических взглядов в статье представлены основные институциональные и индивидуальные акторы, участвовавшие в данной войне.
Особое внимание ориентировано на выявление внешних факторов, воздействовавших на возникновение, развитие и временное окончание активной фазы внутриукраинского конфликта после образования СССР.
В то же время в статье представлена авторская концепция гражданской конфронтации на Украине как перманентного исторического процесса, элементы которого актуальны до настоящего времени.
В тексте также продемонстрирован большой информационный потенциал архивных документов из коллекции «Азбука» для изучения событий, ставших объектом освещения в статье.
The article is dedicated to the events of the Civil War in Ukraine between 1918 and 1920. Analyzed are the practical and ideological levels of the war discourse, anddepicted are theinstitutions and personalities engaged into the events. Special attention is given to the external factors, which contributed to the beginning, development and finish of the conflict in Ukraine after the formation of theUSSR. At the same time, the author’spersonal concept of the Civil War in Ukraine is presented. The events and the historical process behind them are shown to be permanent, depicted patterns and elements can be seen nowadays. The article demonstrates the informative capacity of archival documents from «Azbouka» collection.
Pengembangan Nilai-Nilai Karakter Religius Berbasis Kearifan Lokal pada Siswa MI
Authors: Rahayu Tri 
Published: August 2021

Penelitian ini dilatarbelakangi fenomena semakin memudarnya pengetahuan masyarakat tentang kearifan lokal yang telah menjadi karakter dan filosofi hidup mereka, yaitu membatik. Oleh karena itu, perlu ada upaya untuk terus menggali dan memproteksi kearifan lokal. Penelitian ini merupakan penelitian deskriptif kualitatif dengan pendekatan psikologi pendidikan. Subyek penelitian adalah Kepala Sekolah, guru mata pelajaran batik, Pengawas Sekolah serta siswa kelas V dan kelas VI. Teknik pengumpulan datanya meliputi observasi, wawancara, dan dokumentasi. Adapun teknik analisis data melalui pengumpulan data, reduksi data, penyajian data serta penarikan kesimpulan. Dari penelitian ini diperoleh hasil bahwa proses pembelajaran berbasis kearifan lokal membatik di MI Maarif Giriloyo I dilaksanakan melalui tahap perencanaan (mencakup program tahunan, program semester, silabus, dan RPP); pelaksanaan terdiri atas kegiatan pendahuluan, inti (meliputi eksplorasi, elaborasi, konfirmasi), dan penutup; evaluasi pembelajaran melalui observasi, penilaian diri, dan penilaian antarteman. Sedangkan nilai-nilai karakter religius yang dikembangkan dalam pembelajaran berbasis kearifan lokal membatik di MI Maarif Giriloyo I antara lain: pertama, melalui penciptaan motif batik sebagai pesan dan doa atau harapan yang ditujukan kepada Allah SWT. Kedua, pengembangan karakter religius siswa terintegrasi dalam pelaksanaan pembelajaran di kelas terdiri atas kegiatan pendahuluan, inti, dan penutup.
Efectos de la escritura como proceso en la producción de de textos argumentativos
Authors: Rivera Pulido Yudy Ximena 
Published: August 2021

Este artículo tiene como propósito describir un Proyecto Disciplinar de Aula -PDA desarrollado con estudiantes de 4 ° de primaria. El objetivo de este PDA fue el desarrollar habilidades para producir textos argumentativos a través de la estrategia escritura como proceso. La pregunta que guió este PDA fue: ¿Qué efecto tiene la escritura como proceso en la producción de textos argumentativos de estudiantes de cuarto grado de primaria?proyecto se desarrolló con estudiantes de una institución educativa distrital de la localidad cuarta de Bogotá. Este artículo reúne evidencia teórica y empírica del efecto positivo que tiene la estrategia utilizada en la producción de textos argumentativos, además de confirmar que la argumentación es una actividad inherente al ser humano y que está presente en él desde la niñez.