bluuebunny/crossref_metadata_2025_split huggingface dataset:
Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines Update on the Role of Cytotoxic Chemotherapy and Other Cytotoxic Therapies in the Management of Progressive Glioblastoma in Adults
Authors: Germano Isabelle M. , Ziu Mateo , wen patrick , ormond david ryan , olson jeff 
Published: September 2021

Abstract
Target populationThese recommendations apply to adult patients diagnosed with progressive glioblastoma (pGBM).Question (Q1):In adult patients with pGBM does the use of temozolomide (TMZ) with alternative dosing or the use of TMZ in combination with other cytotoxic treatments result in increased overall survival compared to other chemotherapy?Recommendation:Level III: Adult patients with pGBM might derive benefit in treatment with TMZ especially those who progress after more than 5 months of TMZ-treatment free interval. Level III: Combination of TMZ with other cytotoxic agents such as nitrosourea, cisplatin, electrohypothermia, or tamoxifen is not suggested in adult patients with pGBM as a stand-alone therapy.There is insufficient data to make a recommendation about which alternative TMZ dosing provides the best benefits.Question (Q2):In adult patients with pGBM does the use of systemic or in situ nitrosourea result in increased overall survival compared to other chemotherapy?Recommendation:Level III: In the setting of pGBM, fotemustine is suggested in elderly patients with methylated MGMT promoter status. There is insufficient evidence to compare fotemustine to other nitrosoureas. There is insufficient evidence to make a suggestion about the use of in situ nitrosourea in patients with pGBM who underwent the Stupp regimen.Question (Q3):In adult patients with pGBM does the use of platinum compounds and topoisomerase result in increased survival compared to other chemotherapy?Recommendation:Level III: Other chemotherapy including platinum compounds and topoisomerase inhibitors are not suggested to be used in adult patients with pGBM.Level III: Other cytotoxic therapies like perillyl acohol and ketogenic diet are not suggested for use in adult patients with pGBM as a stand-alone therapy.Question (Q4):In adult patients with pGBM does the use of tumor treating field (TTF) result in increased overall survival compared to chemotherapy?Recommendation:Level III: The use of TTF with other chemotherapy may be considered when treating adult patients with pGBM.There is insufficient evidence to recommend TTF to increase overall survival in adult patients with pGBM.Question (Q5):In adult patients with pGBM does the use of oncolytic virotherapy result in increased survival compared to chemotherapy?Recommendation:Level III: Oncolytic virotherapy is not suggested in patients with pGBM.
Specialist Wait Time Reporting Using Family Physicians’ Electronic Medical Record Data: A Mixed Method Study of Feasibility and Clinical Utility
Authors: Naimer Michelle , Aliarzadeh Babak , Bell Chaim M. , Ivers Noah , Jaakkimainen Liisa , McIsaac Warren , Meaney Christopher , Moineddin Rahim , Permaul Joanne A. , Makuwaza Tutsirai , Kukan Sahana 
Published: September 2021

Abstract
Background: More than 50% of Canadian patients wait longer than four weeks to see a specialist after referral from primary care. Access to accurate wait time information may help primary care physicians choose the timeliest specialist to address a patient’s specific needs. We conducted a mixed-methods study to assess if primary to specialist care wait times can be extracted from electronic medical records (EMR), analyzed the wait time information, and used focus groups and interviews to assess the potential clinical utility of the wait time information. Methods: Two family practices were recruited to examine primary care physician to specialist wait times between 2016 and 2017, using EMR data. The primary outcome was the median wait time from physician referral to specialist appointment for each specialty service. Secondary outcomes included the physician and patient characteristics associated with wait times as well as qualitative analyses of physician interviews about the resulting wait time reports.Results: Wait time data can be extracted from the primary care EMR and converted to a report format for family physicians and specialists to review. After data cleaning, there were 7141 referrals included from 4967 unique patients. The 5 most common specialties referred to were Dermatology, Gastroenterology, Ear Nose and Throat, Obstetrics and Gynecology and Urology. Half of the patients were seen by a specialist within 42 days, 75% seen within 80 days and all patients within 760 days. There were few patient or provider differences amongst the wait times for referrals. Overall, wait time reports were perceived to be important since they could help family physicians decide how to triage referrals and might lead to system improvements. Conclusions: Wait time information from primary to specialist care can aid in decision-making around specialist referrals, identify bottlenecks, and help with system planning. This mixed method study is a starting point to review the importance of providing wait time data for both family physicians and local health systems. Future work can be directed towards developing wait time reporting functionality and evaluating if wait time information will help increase system efficiency and/or improve provider and patient satisfaction.
A pan-cancer analysis of tumor-infiltrating B cell repertoires
Authors: Yu Katharine , Ravoor Akshay , Malats Nuria , Pineda Silvia , Sirota Marina 
Published: September 2021

Abstract
Tumor-infiltrating B cells can play an important role in anti-tumor responses but their presence is not well understood. In this study, we extracted the B cell receptor repertoires from 9522 tumor and adjacent non-tumor samples across 28 tumor types in the Cancer Genome Atlas (TCGA) project and performed diversity and network analysis. We identified differences in diversity and network statistics across tumor types and subtypes and we observed a trend towards increased clonality in primary tumor samples compared to adjacent non-tumor tissues. We also found significant associations between the repertoire features and mutation load, tumor stage, and age. Our V-gene usage analysis identified similar V-gene usage patterns in colorectal and endometrial cancers. Lastly, we evaluated the prognostic value of the repertoire features and identified significant associations with survival in seven tumor types. This study warrants further research into better understanding the role of tumor-infiltrating B cells across a wide range of tumor types.
Turnaround Time for Microbiological Testing of Tuberculosis in Routine Clinical Practice and Time to Patient Initiation on Treatment, Iganga Hospital, Uganda: 2012-2017
Authors: Musewa Angella , Bulage Lilian , Maganda Joseph Frank , Ario Alex Riolexus 
Published: September 2021

Abstract
Background: Multidrug-resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis (Mtb) that is resistant to atleast isoniazid and rifampicin. Delayed diagnosis and treatment initiation lead to increased transmission and poor clinical outcomes. Although GeneXpert MTB/RIF detects Mtb and rifampicin resistance within 2 hours, the TB control program needs to understand the turnaround time (TAT) from specimen collection to treatment initiation and its impact on treatment outcomes for patients with Rif-resistant TB in Uganda. We quantified the TAT overall and at each step of the process for diagnosis of Rif-resistant TB in routine clinical practice and time to initiation on appropriate treatment over a 5-year period.Methods: We conducted a retrospective study in Iganga General Hospital, Eastern Uganda. Both Rif-resistant and MDR TB cases are recorded in the same register. We abstracted data from the MDR-TB clinic and laboratory registers (Form 2A and 096B) at Iganga Hospital, 2012-2017, including dates for smear microscopy, Xpert MTB/RIF, initiating MDR-TB patients on treatment after the Xpert MTB/RIF test, and dates for Drug Susceptibility Testing (DST). We performed descriptive and survival analysis to estimate the TAT for microbiological testing and time to initiation on treatment among MDR-TB patients.Results: Overall, we analyzed sixty-three (63) records, including specimens from Iganga Hospital patients and referrals from other health facilities. Of 63 records, 81% (51/63) had microscopy results, 97% (61/63) had Xpert MTB/RIF results, and 98% (62/63) had DST results. The median TAT for smear microscopy was the same day or within 1 day for 38/51 (75%) of the patients, ranging from 2-31 days for the rest. TAT for Xpert MTB/RIF results was the same day or within 1 day for 45/61 (75%), while the rest ranged from 2-183 days. Treatment initiation was within 28 days for 30/61 (50%). Reporting results for DST, took a median time of 13 days (IQR: 10-40 days) with an overall range of 0-334 days. Conclusion: Prompt Xpert MTB/RIF testing and result reporting allows timely treatment initiation. We recommend timely release of DST results by the National Tuberculosis Reference Laboratory or decentralization of DST services so as to mitigate delays and improve patient re-evaluation.
Effects of Tarragon Hydroalcoholic Extract and Coumarin On Memory, Tissue Index and GABAA Receptor Gene Expression in The Hippocampus of Male Rats
Authors: Heidarieh Nasrin , Najafifard Maryam , Rohani Ali Haeri , Eidi Akram 
Published: September 2021

Abstract
Background and objective:

Learning and memory are necessary for survival. The hippocampus plays a significant role in learning process. GABAA receptors in the hippocampus are effective in learning and memory mechanism. The present study effect of tarragon hydroalcoholic extract and coumarin on memory, tissue index and GABAA receptor gene expression in the hippocampus of male rats.
Methodology:

56 Wistar rats were used and randomized in 7 groups (N = 8). These groups included the intact, receiving DMSO, receiving tarragon hydroalcoholic extract doses of 25, 50 and 100 mg/kg and receiving coumarin dose of 3, 5 mg/kg. They have undergone treatment intraperitoneally once a day for two weeks. The shuttle box was used for the memory retention test. The rats were killed according to the research ethical codes after the tests were done. When the brains of rats were removed, 4 brains in each group were chosen for the histological test using Nissl staining. In the other four brains, the hippocampus was removed immediately. The hippocampus was located in a microtube and was frozen by liquid nitrogen. Finally, a gene expression test was performed using real-time PCR.
Results

the findings of the present study reveal that there was no significant difference between of solvent recipients and the intact group in the memory retention test, the number of healthy hippocampal pyramidal neurons, and the expression of the GABAA gene. The treated groups with various doses of hydroalcoholic extract of tarragon and coumarin showed decreased in the memory retention test and the number of healthy pyramidals neurons as well as a significant increase in GABAA- α5 and GABAA- α2 genes expression compared to the group receiving solvent.
Conclusion

Tarragon hydroalcoholic extract and coumarin affects memory impairment through increasing the GABAA-α5 and GABAA-α2 genes expression and decreasing the number of healthy hippocampal neurons.
Development and Evaluation of a Website With Patients Experiences of Multiple Sclerosis: A Mixed Methods Study
Authors: Sippel Anna , Scheiderbauer Jutta , Eklund Désirée , Arnade Sigrid , Schmidt Stephan , Kleiter Ingo , Morrison Rebecca , Kofahl Christopher , Heesen Christoph 
Published: September 2021

Abstract
Background
A variety of management options (e.g., disease-modifying therapy, lifestyle interventions, rehabilitation) are available for persons with relapsing-remitting multiple sclerosis (MS). Besides coping with the diagnosis, persons with MS have to make complex decisions, e.g., regarding disease-modifying therapies. In addition to factual information, reports of patient experiences may support other patients in their decision-making. Therefore, we developed a website presenting patient experiences illustrated by video, audio and text files. This study aimed to test the acceptability and usability of a website with patient experiences with MS.
Methods
A mixed-methods approach was applied. A total of 69 participants visited the German “Patient Experiences with MS (PExMS)” website and among them, 50 persons with MS and 6 experts completed an online survey. In total, 18 participants took part in telephone interviews or focus groups. Data from the survey were analysed using descriptive statistics. Qualitative data were analysed using thematic analysis.
Results
Both quantitative and qualitative responses suggest that the PExMS website was viewed positively by patients and experts. 94% of persons with MS agreed that the information was comprehensible and reliable. 54% felt encouraged to share their health problems with others after having studied the website. 74% claimed to use the website if they had to make a decision regarding their health. Qualitative responses deduced from the website fell into 5 key themes: (1) web design, appearance, and functionality, (2) content, (3) usability, (4) satisfaction, and (5) loyalty. The search for persons of similar age and with comparable experiences was a major driving force to navigate the website. The material on the website was perceived as diverse, covering both positive and negative experiences in daily living with MS. All participants greatly appreciated having access to other people’s experiences online and judged the material on the website as particularly helpful in decision-making for disease-modifying therapies.
Conclusions
The findings suggest that the PExMS website might have the potential to be a useful source of audio-visual information for persons with MS. Given the lack of websites available to patients with experiential information, health care professionals may be encouraged to routinely inform patients about this website at regular appointments.
Reference-Based Versus Reference-Free Cell Type Estimation In DNA Methylation Studies Using Human Placental Tissue
Authors: Dieckmann Linda , Cruceanu Cristiana , Lahti-Pulkkinen Marius , Lahti Jari , Kvist Tuomas , Laivuori Hannele , Sammallahti Sara , Villa Pia M. , Suomalainen-König Sanna , Rancourt Rebecca C. , Plagemann Andreas , Henrich Wolfgang , Eriksson Johan G. , Kajantie Eero , Entringer Sonja , Braun Thorsten , Raikkonen Katri , Binder Elisabeth B. , Czamara Darina 
Published: September 2021

Abstract
The placenta is a central organ during early development, influencing trajectories of health and disease. DNA methylation (DNAm) studies of human placenta improve our understanding of how its function relates to disease risk. However, DNAm studies can be biased by cell type heterogeneity, so it is essential to control for this in order to reduce confounding and increase precision. Computational cell type deconvolution approaches have proven to be very useful for this purpose. For human placenta, however, an assessment of the performance of these estimation methods is still lacking. Here, we compare the predictive performance of reference-based versus reference-free estimated proportions of cell types from genome-wide DNAm in placental samples taken at birth and from chorion villus biopsies early in pregnancy using three independent studies comprising over 1,000 samples. We found both reference-free and reference-based estimated cell type proportions to have predictive value for DNAm, however, reference-based cell type estimation outperformed reference-free estimation for the majority of data sets. Reference-based cell type estimations mirror previous histological knowledge on changes in cell type proportions through gestation. Further, CpGs whose variation in DNAm was largely explained by reference-based estimated cell type proportions were in the proximity of genes that are highly tissue-specific for placenta. This was not the case for reference-free estimated cell type proportions. We provide a list of these CpGs as a resource to help researchers to interpret results of existing studies and improve future DNAm studies of human placenta.
PCGF2 and PCGF4 Opposite Drive Stem-like Properties in Hepatocellular Carcinoma
Authors: Hu Jinjing , Zhou Yongqiang , Feng Huan , Xie Yi , Qi Kuo , Chen Yonglin , Meng Wenbo , Ma Xiaojun , Wei Yongjian , Lu Fei , Yao Jia , Cheng Bo , Li Xun 
Published: September 2021

Abstract
Background: PCGF4 is highly expressed in liver cancer and can be used as a marker for liver cancer stem cells. However, PCGF2, a homologue of PCGF4, is not clear whether it is expressed in HCC, and whether it regulates the stemness of liver cancer stem cells.Methods: IHC and Western blot were used to detect the expression of PCGF2 and PCGF4 protein in human HCC tissues and cell lines. Flow cytometry and sphere formation were performed to detect the effect of PCGF2 or PCGF4 on the stem-like properties of liver cancer stem cells. Kaplan-Meier curves were conducted for OS and DFS. Cell viability was measured at the indicated time points using Cell Counting Kit-8. We performed KEGG analysis on these target genes through the cluster profiler package of the R language.Results: IHC results showed that PCGF2 was lower expressed in HCC, while PCGF4 was higher expressed in HCC compared with matched paracancerous, and this higher expression exhibited poor prognosis in HCC. Up regulation of PCGF2 was also accompanied with decreased stem-like properties and sphere formation in HCC cell lines. Interestingly, down regulating PCGF4 got the similar results as up regulating PCGF2. Furthermore, up regulating PCGF2 or down regulating PCGF4 cells performed more sensitivity to sorafenib. We also found that PCGF2 and PCGF4 oppositely regulated the drives stem-like properties by p38 MAPK signal pathway.Conclusion: PCGF2 was a novel negative regulator of LCSCs that inhibiting the stem cell population, reducing the sphere formation ability of liver cancer stem cells, and increasing the sensitivity of sorafenib by targeting p38 MAPK signaling. PCGF2 was supposed to be a novel therapeutic target for Liver cancer stem cell.
Comparative Transcriptome Analysis of Preterm Placental Tissue with Maternal Diabetes, Obesity and Periodontitis Diseases Using Integrated Bioinformatics Approach
Authors: Amin Humaira , Bokhari Syed Habib , Shahzad Khuram 
Published: September 2021

Abstract
Preterm birth (PTB) is one of the major reasons of infant mortalities and morbidities worldwide. Exact mechanism of this disease has not been elucidated yet but studies have shown several factors which have been found associated with the disease. Through several studies, it has been discovered that different chronic diseases like obesity, type 1 diabetes and periodontitis are also associated with PTB but no omics studies have yet been performed to discover their association. In the current study, comparative transcriptome analysis of the preterm birth with type 1 diabetes, obesity and periodontitis using integrated bioinformatics approach was performed to validate their association with preterm birth. Four different datasets retrieved from Gene expression omnibus (GEO) were processed through Bioconductor packages in R. Pairwise comparison of preterm was performed with all three diseases. Several bioinformatics tools were used such as DAVID for Gene ontology (GO) terms and pathway analysis, DIA for impact and direction of KEGG pathways and Cytoscape along with its different plugins for construction of networks, identification of hub genes and modules. Significant number of common differentially expressed genes between datasets and their roles in different pathways were identified. Most of the significant genes and pathways found in these comparisons were involved in initiating different inflammatory processes, degradation of proteins leading to preterm premature rupture of membranes (PPROM), preeclampsia, and cancer which are the known risk factors of PTB. According to our results, all these three chronic diseases were found to have a strong association with PTB.
Highly Transparent and Tunable Antenna Window Using Saltwater for UHF Band Applications
Authors: Phan Duy Tung , Nguyen Tien Dat , Jung Chang Won 
Published: September 2021

Abstract
This paper presents a highly optical transparent and tunable liquid antenna for applications on the UHF band. The antenna has high transparency (> 91%), which is achieved through its use of salty water as a conductive medium held within a clear and hollow acrylic rectangular prism, allowing its use as an optical window. To achieve frequency- and beam-tunable characteristics, two advanced configurations of the antenna using dual-port feeding are proposed. The antenna’s performance is simulated and then verified through experiments. Measurement results show that for a basic configuration using single-port feeding, the antenna has a −6 dB bandwidth ranging from 350 to 675 MHz and efficient radiation efficiency (> 60%) over the band. For advanced configurations, a tunable frequency and directional radiation pattern can be achieved with enhancing gain compared to the basic configuration. These results demonstrate the proposed antenna can be used as a bi-functional device, i.e., as atunable antenna and optical window.
Viromic Analysis of Feces From Laboratory Rabbits Reveals a Novel Circovirus
Authors: Ning Song-Yi , Xiao Yu-Qing , Qain Yu-Chen , Feng Zhang-Hao , Dai Zi-yuan , Zhang Wen , Wang Hao , Tang Yuan-Jie 
Published: September 2021

Abstract
Circoviruses are responsible for fatal diseases that can affect mammals and birds. Beak and feather disease virus (BFDV) is responsible for fatal diseases of birds, causing the psittacine beak and feather disease. The current study discovered a novel circovirus named RabCV from feces of laboratory rabbits, which shows close relationship to BFDVs. This novel circovirus was discovered from feces of rabbits, which showed low prevalence in the healthy laboratory rabbits. BFDV is responsible for fatal diseases that could affect birds, which suggested that the potential threat of the novel rabbit circovirus to the health of laboratory rabbits needs further study.
Phenotype of Higher Post-load Insulin Response as a Predictor of All-cause Mortality and Cardiovascular Mortality in the Chinese Non-diabetes Population
Authors: Shen Xiaoxia , He Siyao , Wang Jinping , Qian Xin , Wang Hui , Zhang Bo , Chen Yanyan , Li Hui , Li Guangwei 
Published: September 2021

Abstract
Background This study aimed to assess whether a higher insulin response increased the long-term risk of mortality in a non-diabetes population.Methods A total of 446 non-diabetes who participated in the Da Qing Diabetes Study were stratified into quartiles subgroups according to their baseline insulin area under the curve (AUC) during oral glucose tolerance test, defined as Q1, Q2, Q3 and Q4. The insulin AUC increased drastically from 75.23, 129.61, 179.06 to 309.85mU/L across the four groups. The participants were followed from 1986 to 2016 to assess the risk of death in association with the magnitude of post-load insulin response.Results The rates of all-cause death in participants who were assigned in the highest (Q4) and lowest (Q1) quartiles of insulin AUC groups were 17.58/1000 and 9.94/1000 person years during a 30-year period, respectively. Multiple Cox analyses with adjustment for baseline age, sex, smoking, post load glucose and other potential confounders showed that the risks of all-cause death in the Group 4 was significantly higher than Group 1(HR 1.90, 95% CI:1.12-3.23). The CVD death rate across these subgroups showed a similar trend (10.47/1000 person years in Group 4 vs 5.14/1000 person years in Group 1) as all-cause death, but it was not significantly different after the same adjustment. Conclusions A higher post-load insulin response was significantly associated with a long-term increased risk of all-cause mortality in the Chinese non-diabetes population. Therefore, subjects featured by this phenotype was a potential important target for further intervention.