bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in epigenetic therapeutics with focus on solid tumors
Authors: Jin Ning , George Tiffany L. , Otterson Gregory A. , Verschraegen Claire , Wen Haitao , Carbone David , Herman James , Bertino Erin M. , He Kai 
Published: April 2021

AbstractEpigenetic (“above genetics”) modifications can alter the gene expression without altering the DNA sequence. Aberrant epigenetic regulations in cancer include DNA methylation, histone methylation, histone acetylation, non-coding RNA, and mRNA methylation. Epigenetic-targeted agents have demonstrated clinical activities in hematological malignancies and therapeutic potential in solid tumors. In this review, we describe mechanisms of various epigenetic modifications, discuss the Food and Drug Administration-approved epigenetic agents, and focus on the current clinical investigations of novel epigenetic monotherapies and combination therapies in solid tumors.
Prognostic value of amyloid/tau/neurodegeneration (ATN) classification based on diagnostic cerebrospinal fluid samples for Alzheimer’s disease
Authors: Delmotte Koen , Schaeverbeke Jolien , Poesen Koen , Vandenberghe Rik 
Published: April 2021

Abstract
Objective
The primary study objective of this retrospective academic memory clinic-based observational longitudinal study was to investigate the prognostic value of a cerebrospinal fluid (CSF)-based ATN classification for subsequent cognitive decline during the 3 years following lumbar puncture in a clinical, real-life setting. The secondary objective was to investigate the prognostic value of CSF biomarkers as continuous variables.

Methods
Data from 228 patients (median age 67 (47–85) years), who presented at the Neurology Memory Clinic UZ/KU Leuven between September 2011 and December 2016, were included with a follow-up period of up to 36 months. Patients underwent a CSF AD biomarker test for amyloid-beta 1–42 (Aβ42), hyperphosphorylated tau (p181-tau) and total tau (t-tau) in the clinical work-up for diagnostic reasons. Patients were divided into ATN classes based on CSF biomarkers: Aβ42 for amyloid (A), p181-tau for tau (T), and t-tau as a measure for neurodegeneration (N). Based on retrospective data analysis, cognitive performance was evaluated by Mini Mental State Examination (MMSE) scores every 6 months over a period up to 36 months following the lumbar puncture. The statistical analysis was based on linear mixed-effects modeling (LME).

Results
The distribution in the current clinical sample was as follows: A−/T−/N− 32.02%, A+/T−/N− 33.33%, A+/T+/N+ 17.11%, A+/T−/N+ 11.84%, A−/T−/N+ 4.39%, A−/T+/N+ 1.32% (3 cases), with no cases in the A−/T+/N− and A+/T+/N− class. Hence, the latter 3 classes were excluded from further analyses. The change of MMSE relative to A−/T−/N− over a 36-month period was significant in all four ATN classes: A+/T+/N+ = − 4.78 points on the MMSE; A−/T−/N+ = − 4.76; A+/T−/N+ = − 2.83; A+/T−/N− = − 1.96. The earliest significant difference was seen in the A+/T+/N+ class at 12 months after baseline. The effect of ATN class on future cognitive decline was confirmed for a different set of CSF thresholds. All individual baseline CSF biomarkers including the Aβ42/t-tau ratio showed a significant correlation with subsequent cognitive decline, with the highest correlation seen for Aβ42/t-tau.

Conclusion
ATN classification based on CSF biomarkers has a statistically significant and clinically relevant prognostic value for the course of cognitive decline in a 3-year period in a clinical practice setting.
Use of the Clock Drawing Test and the Rey–Osterrieth Complex Figure Test-copy with convolutional neural networks to predict cognitive impairment
Authors: Youn Young Chul , Pyun Jung-Min , Ryu Nayoung , Baek Min Jae , Jang Jae-Won , Park Young Ho , Ahn Suk-Won , Shin Hae-Won , Park Kwang-Yeol , Kim Sang Yun 
Published: April 2021

Abstract
Background
The Clock Drawing Test (CDT) and Rey–Osterrieth Complex Figure Test (RCFT) are widely used as a part of neuropsychological test batteries to assess cognitive function. Our objective was to confirm the prediction accuracies of the RCFT-copy and CDT for cognitive impairment (CI) using convolutional neural network algorithms as a screening tool.

Methods
The CDT and RCFT-copy data were obtained from patients aged 60–80 years who had more than 6 years of education. In total, 747 CDT and 980 RCFT-copy figures were utilized. Convolutional neural network algorithms using TensorFlow (ver. 2.3.0) on the Colab cloud platform (www.colab.research.google.com) were used for preprocessing and modeling. We measured the prediction accuracy of each drawing test 10 times using this dataset with the following classes: normal cognition (NC) vs. mildly impaired cognition (MI), NC vs. severely impaired cognition (SI), and NC vs. CI (MI + SI).

Results
The accuracy of the CDT was better for differentiating MI (CDT, 78.04 ± 2.75; RCFT-copy, not being trained) and SI from NC (CDT, 91.45 ± 0.83; RCFT-copy, 90.27 ± 1.52); however, the RCFT-copy was better at predicting CI (CDT, 77.37 ± 1.77; RCFT, 83.52 ± 1.41). The accuracy for a 3-way classification (NC vs. MI vs. SI) was approximately 71% for both tests; no significant difference was found between them.

Conclusions
The two drawing tests showed good performance for predicting severe impairment of cognition; however, a drawing test alone is not enough to predict overall CI. There are some limitations to our study: the sample size was small, all the participants did not perform both the CDT and RCFT-copy, and only the copy condition of the RCFT was used. Algorithms involving memory performance and longitudinal changes are worth future exploration. These results may contribute to improved home-based healthcare delivery.
Mimickers of breast malignancy: imaging findings, pathologic concordance and clinical management
Authors: Guirguis Mary S. , Adrada Beatriz , Santiago Lumarie , Candelaria Rosalind , Arribas Elsa 
Published: April 2021

AbstractMany benign breast entities have a clinical and imaging presentation that can mimic breast cancer. The purpose of this review is to illustrate the wide spectrum of imaging features that can be associated with benign breast diseases with an emphasis on the suspicious imaging findings associated with these benign conditions that can mimic cancer. As radiologic-pathologic correlation can be particularly challenging in these cases, the radiologist’s familiarity with these benign entities and their imaging features is essential to ensure that a benign pathology result is accepted as concordant when appropriate and that a suitable management plan is formulated.
Efficacy and safety of mesenchymal stem cells co-infusion in allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis
Authors: Li Teng , Luo Chengxin , Zhang Jiasi , Wei Ling , Sun Wei , Xie Qin , Liu Yan , Zhao Yongli , Xu Shuangnian , Wang Lihua 
Published: April 2021

Abstract
Background
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is life-saving for severe hematological conditions. However, its outcomes need further improvement, and co-infusion of mesenchymal stem cells (MSCs) may show promise. A growing body of research on this subject exists, while the results of different trials are conflicting. A systematic review and meta-analysis is needed to appraise the real efficacy and safety of MSC co-transplantation in allo-HSCT.

Methods
Studies comparing MSC co-transplantation in allo-HSCT with allo-HSCT alone were searched in six medical databases from inception to June 10, 2020. The primary outcomes were engraftment and graft-versus-host disease (aGVHD and cGVHD, respectively). Other outcomes included overall survival (OS), relapse rate (RR), non-relapse mortality (NRM), and immune reconstitution. Information was independently extracted by two investigators. Methodological quality was assessed using the Cochrane Collaboration tool. Meta-analysis was performed using RevMan 5.4.

Results
Six randomized controlled trials (RCTs) and 13 non-randomized controlled trials (nRCTs) were included. MSC co-infusion resulted in shorter times to neutrophil engraftment (RCTs: standardized mean difference (SMD) − 1.20, p = 0.04; nRCTs: SMD − 0.54, p = 0.04) and platelet engraftment (RCTs: SMD − 0.60, p = 0.04; nRCTs: SMD − 0.70, p = 0.01), a lower risk of cGVHD (RCTs: risk ratio (RR) 0.53, p = 0.01; nRCTs: RR 0.50, p <  0.01), and a slightly positive trend towards reducing the risk of aGVHD and NRM, without affecting RR and OS. Subgroup analyses revealed that when MSCs were co-transplanted, children and adolescents, and patients receiving human leukocyte antigen (HLA)-nonidentical HSCT showed improvements in engraftment and incidence of GVHD and NRM; adults and patients who received HLA-identical HSCT had lower cGVHD; patients with malignancies exhibited improvements in GVHD and NRM incidence; and patients with non-malignancies experienced accelerated engraftment. Notably, a reduced OS was observed in patients with hematological malignancies undergoing HLA-identical HSCT.

Conclusion
MSC co-infusion generally improved engraftment and reduced cGVHD, without increasing mortality or relapse. Regarding aGVHD and NRM, the effects of MSCs were not quite significant. Specifically, our data support the utilization of MSC co-transplantation in children and young individuals with HLA-nonidentical HSCT, but not in adult patients with hematological malignancies undergoing HLA-identical HSCT.
ABO blood types and sepsis mortality
Authors: Itenov Theis S. , Sessler Daniel I. , Khanna Ashish K. , Ostrowski Sisse R. , Johansson Pär I. , Erikstrup Christian , Pedersen Ole B. , Rygård Sofie L. , Holst Lars B. , Bestle Morten H. , Hein Lars , Lindhardt Anne , Tousi Hami , Andersen Mads H. , Mohr Thomas , Lundgren Jens D. , Jensen Jens-Ulrik 
Published: April 2021

Abstract
Background
We aimed to determine if the ABO blood types carry different risks of 30-day mortality, acute kidney injury (AKI), and endothelial damage in critically ill patients with sepsis. This was a retrospective cohort study of three independent cohorts of critically ill patients from the United States and Scandinavia consisting of adults with septic shock. We compared the 30-day mortality across the blood types within each cohort and pooled the results in a meta-analysis. We also estimated the incidence of AKI and degree of endothelial damage, as measured by blood concentrations of soluble thrombomodulin and syndecan-1.

Results
We included 12,342 patients with severe sepsis. In a pooled analysis blood type B carried a slightly lower risk of 30-day all-cause mortality compared to non-blood type B (adjusted HR 0.88; 95%-CI 0.79–0.98; p = 0.02). There was no difference in the risk of AKI. Soluble thrombomodulin and syndecan-1 concentrations were lower in patients with blood type B and O compared to blood type A, suggesting less endothelial damage.

Conclusion
Septic patients with blood type B had less endothelial damage, and a small reduction in mortality. The exposure is, however, unmodifiable.
Discrete choice experiment to determine preferences of decision-makers in healthcare for different formats of rapid reviews
Authors: Speckemeier Christian , Krabbe Laura , Schwenke Susanne , Wasem Jürgen , Buchberger Barbara , Neusser Silke 
Published: April 2021

Abstract
Background
Time-saving formats of evidence syntheses have been developed to fulfill healthcare policymakers’ demands for timely evidence-based information. A discrete choice experiment (DCE) with decision-makers and people involved in the preparation of evidence syntheses was undertaken to elicit preferences for methodological shortcuts in the conduct of abbreviated reviews.

Methods
D-efficient scenarios, each containing 14 pairwise comparisons, were designed for the DCE: the development of an evidence synthesis in 20 working days (scenario 1) and 12 months (scenario 2), respectively. Six attributes (number of databases, number of reviewers during screening, publication period, number of reviewers during data extraction, full-text analysis, types of HTA domains) with 2 to 3 levels each were defined. These were presented to the target population in an online survey. The relative importance of the individual attributes was determined using logistic regression models.

Results
Scenario 1 was completed by 36 participants and scenario 2 by 26 participants. The linearity assumption was confirmed by the full model. In both scenarios, the linear difference model showed a preference for higher levels for “number of reviewers during data extraction”, followed by “number of reviewers during screening” and “full-text analysis”. Subgroup analyses showed that preferences were influenced by participation in the preparation of evidence syntheses.

Conclusion
The surveyed persons expressed preferences for quality standards in the process of literature screening and data extraction.
Application of triple compound combination anti-synchronization among parallel fractional snap systems & electronic circuit implementation
Authors: Mahmoud Emad E. , Trikha Pushali , Jahanzaib Lone Seth , Higazy M. , Alkinani Monagi H. 
Published: April 2021

AbstractIn this article we examine the dynamical properties of the fractional version of the snap system by means of chaotic attractor, existence, and uniqueness of the solution, symmetry, dissipativity, stagnation point analysis, Lyapunov dynamics, K.Y. dimension, bifurcation diagram, etc. Also, parallel systems to this system are synchronized in presence of uncertainties and external disturbances using triple compound combination anti-synchronization by two ways. Synchronization time is compared with some other works. Also the utilization of achieved synchronization is illustrated in secure transmission. By constructing the snap system’s signal flow graph and its real electronic circuit, some of its additional invariants are investigated.
Individual and community-level determinants of childhood vaccination in Ethiopia
Authors: Fenta Setegn Muche , Fenta Haile Mekonnen 
Published: April 2021

Abstract
Background
Vaccines are one of our most important tools for preventing outbreaks and keeping the world safe. Most unvaccinated children live in the poorest countries including Ethiopia. Therefore, this study aimed to identify the determinants of vaccination coverage among children aged12–23 months in Ethiopia.

Methods
A cross-sectional secondary data were obtained from the 2016 Ethiopian Demographic and Health Survey data (EDHS). A total of 1929 children were included. A Multilevel Proportional Odds Model was used to identify the individual and community-level factors associated with child vaccination.

Result
Among 1, 929 children, only 48.6% (95% CI: 46.3 to 50.8%) were fully vaccinated while 37.8% (95% CI: 35.7 to 40.1%) were partially vaccinated.. The multilevel ordinal logistic regression model reveled that housewife mother (AOR =1.522, 95%CI: 1.139, 2.034), institutional delivery (AOR =2.345, 95%CI: 1.766, 3.114),four or above antenatal care visits (AOR = 2.657; 95% CI: 1.906, 3.704), children of mothers with secondary or higher education (AOR = 2.008; 95% CI: 1.209, 3.334),Children whose fathers primary education (AOR = 1.596; 95% CI: 1.215, 2.096), from the rich households (AOR = 1.679; 95% CI: 1.233, 2.287) were significantly associated with childhood vaccination.

Conclusion
Child vaccination coverage in Ethiopia remains low. Therefore, there is a need to increase child vaccination coverage by promoting institutional delivery and prenatal care visits, as well as maternal tetanus immunization. Besides, public initiatives needed to improve child vaccination coverage, women’s and husband’s education, poor women, and further advancement of health care services for poor women, housewife women, women living in remote areas should be made to maintain further improvements in child vaccination. Furthermore, policies and programs aimed at addressing cluster variations in child vaccination need to be formulated and their implementation must be strongly pursued.
Is telemedicine the answer to rural expansion of medication treatment for opioid use disorder? Early experiences in the feasibility study phase of a National Drug Abuse Treatment Clinical Trials Network Trial
Authors: Hser Yih-Ing , Ober Allison J. , Dopp Alex R. , Lin Chunqing , Osterhage Katie P. , Clingan Sarah E. , Mooney Larissa J. , Curtis Megan E. , Marsch Lisa A. , McLeman Bethany , Hichborn Emily , Lester Laurie S. , Baldwin Laura-Mae , Liu Yanping , Jacobs Petra , Saxon Andrew J. 
Published: April 2021

AbstractTelemedicine (TM) enabled by digital health technologies to provide medical services has been considered a key solution to increasing health care access in rural communities. With the immediate need for remote care due to the COVID-19 pandemic, many health care systems have rapidly incorporated digital technologies to support the delivery of remote care options, including medication treatment for individuals with opioid use disorder (OUD). In responding to the opioid crisis and the COVID-19 pandemic, public health officials and scientific communities strongly support and advocate for greater use of TM-based medication treatment for opioid use disorder (MOUD) to improve access to care and have suggested that broad use of TM during the pandemic should be sustained. Nevertheless, research on the implementation and effectiveness of TM-based MOUD has been limited. To address this knowledge gap, the National Drug Abuse Treatment Clinical Trials Network (CTN) funded (via the NIH HEAL Initiative) a study on Rural Expansion of Medication Treatment for Opioid Use Disorder (Rural MOUD; CTN-0102) to investigate the implementation and effectiveness of adding TM-based MOUD to rural primary care for expanding access to MOUD. In preparation for this large-scale, randomized controlled trial incorporating TM in rural primary care, a feasibility study is being conducted to develop and pilot test implementation procedures. In this commentary, we share some of our experiences, which include several challenges, during the initial two-month period of the feasibility study phase. While these challenges could be due, at least in part, to adjusting to the COVID-19 pandemic and new workflows to accommodate the study, they are notable and could have a substantial impact on the larger, planned pragmatic trial and on TM-based MOUD more broadly. Challenges include low rates of identification of risk for OUD from screening, low rates of referral to TM, digital device and internet access issues, workflow and capacity barriers, and insurance coverage. These challenges also highlight the lack of empirical guidance for best TM practice and quality remote care models. With TM expanding rapidly, understanding implementation and demonstrating what TM approaches are effective are critical for ensuring the best care for persons with OUD.
Impact of sugar beet pulp and wheat bran on serum biochemical profile, inflammatory responses and gut microbiota in sows during late gestation and lactation
Authors: Shang Qinghui , Liu Sujie , Liu Hansuo , Mahfuz Shad , Piao Xiangshu 
Published: April 2021

Abstract
Background
Sows are frequently subjected to various stresses during late gestation and lactation, which trigger inflammatory response and metabolic disorders. Dietary fiber can influence animal health by modulating gut microbiota and their by-products, with the effects depending upon the source of the dietary fiber. This study aimed to evaluate the impacts of different fiber sources on body condition, serum biochemical parameters, inflammatory responses and fecal microbiota in sows from late gestation to lactation.

Methods
Forty-five multiparous sows (Yorkshire × Landrace; 3–6 parity) were assigned to 1 of 3 dietary treatments from d 85 of gestation to the end of lactation (d 21 post-farrowing): a control diet (CON, a corn-soybean meal diet), a sugar beet pulp diet (SBP, 20% SBP during gestation and 10% SBP during lactation), and a wheat bran diet (WB, 30% WB during gestation and 15% WB during lactation).

Results
Compared with CON, supplementation of SBP decreased (P < 0.05) lactation BW loss, reduced (P < 0.05) serum concentration of total cholesterol, non-esterified fatty acids, interleukin-6 and tumor necrosis factor-α, and increased (P < 0.05) fecal water content on d 110 of gestation and d 21 of lactation, while supplementation of WB reduced (P < 0.05) serum concentration of total cholesterol on d 110 of gestation, increased (P < 0.05) fecal water content and decreased (P < 0.05) serum interleukin-6 concentration on d 110 of gestation and d 21 of lactation. In addition, sows fed SBP had lower (P < 0.01) abundance of Clostridium_sensu_stricto_1 and Terrisporobacter than those fed CON, but had greater (P < 0.05) abundance of Christensenellaceae_R-7_group and Ruminococcaceae_UCG-002 than those fed the other two diets on d 110 of gestation. On d 21 of lactation, supplementation of SBP decreased (P < 0.05) the abundance of Firmicutes and Lactobacillus, but enriched (P < 0.05) the abundance of Christensenellaceae_R-7_group, Prevotellaceae_NK3B31_group, Ruminococcaceae_UCG-002, Prevotellaceae_UCG_001 and unclassified_f__Lachnospiraceae compared with WB. Compared with CON, sows fed SBP had greater (P < 0.05) fecal concentrations of acetate, butyrate and total SCFAs during gestation and lactation, while sows fed WB only had greater (P < 0.05) fecal concentration of butyrate during lactation.

Conclusions
Supplementation of dietary fiber during late gestation and lactation could improve sow metabolism and gut health, and SBP was more effective than WB.
The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice
Authors: Barretto Sharon Ann , Lasserre Frederic , Huillet Marine , Régnier Marion , Polizzi Arnaud , Lippi Yannick , Fougerat Anne , Person Elodie , Bruel Sandrine , Bétoulières Colette , Naylies Claire , Lukowicz Céline , Smati Sarra , Guzylack Laurence , Olier Maïwenn , Théodorou Vassilia , Mselli-Lakhal Laila , Zalko Daniel , Wahli Walter , Loiseau Nicolas , Gamet-Payrastre Laurence , Guillou Hervé , Ellero-Simatos Sandrine 
Published: April 2021

Abstract
Background
The gut microbiota–intestine–liver relationship is emerging as an important factor in multiple hepatic pathologies, but the hepatic sensors and effectors of microbial signals are not well defined.

Results
By comparing publicly available liver transcriptomics data from conventional vs. germ-free mice, we identified pregnane X receptor (PXR, NR1I2) transcriptional activity as strongly affected by the absence of gut microbes. Microbiota depletion using antibiotics in Pxr+/+vs Pxr-/- C57BL/6J littermate mice followed by hepatic transcriptomics revealed that most microbiota-sensitive genes were PXR-dependent in the liver in males, but not in females. Pathway enrichment analysis suggested that microbiota–PXR interaction controlled fatty acid and xenobiotic metabolism. We confirmed that antibiotic treatment reduced liver triglyceride content and hampered xenobiotic metabolism in the liver from Pxr+/+ but not Pxr-/- male mice.

Conclusions
These findings identify PXR as a hepatic effector of microbiota-derived signals that regulate the host’s sexually dimorphic lipid and xenobiotic metabolisms in the liver. Thus, our results reveal a potential new mechanism for unexpected drug–drug or food–drug interactions.