bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baricitinib-associated changes in global gene expression during a 24-week phase II clinical systemic lupus erythematosus trial implicates a mechanism of action through multiple immune-related pathways
Authors: Dörner Thomas , Tanaka Yoshiya , Petri Michelle A , Smolen Josef S , Wallace Daniel J , Dow Ernst R , Higgs Richard E , Rocha Guilherme , Crowe Brenda , Benschop Robert J , Byers Nicole L , Silk Maria E , de Bono Stephanie , Fantini Damiano , Hoffman Robert W 
Published: October 2020

ObjectiveTo characterise the molecular pathways impacted by the pharmacologic effects of the Janus kinase (JAK) 1 and JAK2 inhibitor baricitinib in SLE.MethodsIn a phase II, 24-week, randomised, placebo-controlled, double-blind study (JAHH), RNA was isolated from whole blood in 274 patients and analysed using Affymetrix HTA2.0 array. Serum cytokines were measured using ultrasensitive quantitative assays.ResultsGene expression profiling demonstrated an elevation ofSTAT1,STAT2and multiple interferon (IFN) responsive genes at baseline in patients with SLE. Statistical and gene network analyses demonstrated that baricitinib treatment reduced the mRNA expression of functionally interconnected genes involved in SLE includingSTAT1-target,STAT2-target andSTAT4-target genes and multiple IFN responsive genes. At baseline, serum cytokines IFN-α, IFN-γ, interleukin (IL)-12p40 and IL-6 were measurable and elevated above healthy controls. Treatment with baricitinib significantly decreased serum IL-12p40 and IL-6 cytokine levels at week 12, which persisted through week 24.ConclusionBaricitinib treatment induced significant reduction in the RNA expression of a network of genes associated with the JAK/STAT pathway, cytokine signalling and SLE pathogenesis. Baricitinib consistently reduced serum levels of two key cytokines implicated in SLE pathogenesis, IL-12p40 and IL-6.
Targeting Oncogene mRNA Translation in B-Cell Malignancies with eFT226, a Potent and Selective Inhibitor of eIF4A
Authors: Thompson Peggy A. , Eam Boreth , Young Nathan P. , Fish Sarah , Chen Joan , Barrera Maria , Howard Haleigh , Sung Eric , Parra Ana , Staunton Jocelyn , Chiang Gary G. , Gerson-Gurwitz Adina , Wegerski Christopher J. , Nevarez Andres , Clarine Jeff , Sperry Samuel , Xiang Alan , Nilewski Christian , Packard Garrick K. , Michels Theodore , Tran Chinh , Sprengeler Paul A. , Ernst Justin T. , Reich Siegfried H. , Webster Kevin R. 
Published: October 2020

Abstract
The PI3K/AKT/mTOR pathway is often activated in lymphoma through alterations in PI3K, PTEN, and B-cell receptor signaling, leading to dysregulation of eIF4A (through its regulators, eIF4B, eIF4G, and PDCD4) and the eIF4F complex. Activation of eIF4F has a direct role in tumorigenesis due to increased synthesis of oncogenes that are dependent on enhanced eIF4A RNA helicase activity for translation. eFT226, which inhibits translation of specific mRNAs by promoting eIF4A1 binding to 5′-untranslated regions (UTR) containing polypurine and/or G-quadruplex recognition motifs, shows potent antiproliferative activity and significant in vivo efficacy against a panel of diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma models with ≤1 mg/kg/week intravenous administration. Evaluation of predictive markers of sensitivity or resistance has shown that activation of eIF4A, mediated by mTOR signaling, correlated with eFT226 sensitivity in in vivo xenograft models. Mutation of PTEN is associated with reduced apoptosis in vitro and diminished efficacy in vivo in response to eFT226. In models evaluated with PTEN loss, AKT was stimulated without a corresponding increase in mTOR activation. AKT activation leads to the degradation of PDCD4, which can alter eIF4F complex formation. The association of eFT226 activity with PTEN/PI3K/mTOR pathway regulation of mRNA translation provides a means to identify patient subsets during clinical development.
Precision Prevention and Cancer Interception: The New Challenges of Liquid Biopsy
Authors: Serrano Maria Jose , Garrido-Navas Maria Carmen , Diaz Mochon Juan Jose , Cristofanilli Massimo , Gil-Bazo Ignacio , Pauwels Patrick , Malapelle Umberto , Russo Alessandro , Lorente Jose A. , Ruiz-Rodriguez Antonio J. , Paz-Ares Luis G. , Vilar Eduardo , Raez Luis E. , Cardona Andres F. , Rolfo Christian 
Published: October 2020

Abstract
Despite major therapeutic progress, most advanced solid tumors are still incurable. Cancer interception is the active way to combat cancer onset, and development of this approach within high-risk populations seems a logical first step. Until now, strategies for the identification of high-risk subjects have been based on low-sensitivity and low-specificity assays. However, new liquid biopsy assays, “the Rosetta Stone of the new biomedicine era,” with the ability to identify circulating biomarkers with unprecedented sensitivity, promise to revolutionize cancer management. This review focuses on novel liquid biopsy approaches and the applications to cancer interception. Cancer interception involves the identification of biomarkers associated with developing cancer, and includes genetic and epigenetic alterations, as well as circulating tumor cells and circulating epithelial cells in individuals at risk, and the implementation of therapeutic strategies to prevent the beginning of cancer and to stop its development. Large prospective studies are needed to confirm the potential role of liquid biopsy for early detection of precancer lesions and tumors.
Evaluation of IMERG V05B 30-Min Rainfall Estimates over the High-Elevation Tropical Andes Mountains
Authors: Bulovic Nevenka , McIntyre Neil , Johnson Fiona 
Published: October 2020

AbstractSatellite-based estimates of rainfall are frequently used to complement scarce networks of gauges. Understanding uncertainties is an important step, but it is often hindered by a lack of validation data or misrepresented by spatial-scale-related uncertainties, which are especially important in spatially variable regions such as mountains. This study evaluates the Integrated Multisatellite Retrievals for GPM (IMERG) V05B 30-min estimates for all three runs (Early, Late, Final) over the high tropical Andes. A unique dataset containing 15 rain gauges located within one IMERG grid at elevations ranging from 3800 to 4600 m provides a first evaluation opportunity in this topographical context. The evaluation was based on categorical, statistical, and graphical methods. Error dependencies on precipitation characteristics and data source of the IMERG estimate were investigated. We show that IMERG severely underdetects precipitation events, thus underestimating precipitation depths. Poor detection is partially attributable to the low-intensity nature of precipitation over the region. However, tracing the error to the data source highlights limitations in passive microwave retrievals over the full range of intensities. No IMERG run has best overall performance, emphasizing that run suitability is application specific. The impact of gauge density on performance metrics was also evaluated and showed that subdaily IMERG accuracy is overestimated by sparse networks. A minimum of six gauges was required at the 30-min increment so that performance metrics are within 0.1 points of their true scores. We provide the first comprehensive assessment of 30-min IMERG in a mountainous setting, highlighting the importance of high-density networks for accurate subdaily evaluations.
Determinants of treatment disengagement among those at risk of suicide referred to primary mental health care services in Western Sydney, Australia
Authors: Munasinghe Sithum , Page Andrew , Mannan Haider , Ferdousi Shahana , Peek Brendan 
Published: October 2020

Objective: Continued engagement with primary mental health services has been associated with the prevention of subsequent suicidal behaviour; however, there are few studies that identify determinants of treatment disengagement among those at risk of suicide in primary care settings. This study investigated determinants of treatment disengagement of those at risk of suicide who were referred to primary mental health care services in Western Sydney, Australia. Method: This study used routinely collected data of those referred for suicide prevention services provided through primary mental health care services between July 2012 and June 2018. Associations between sociodemographic, diagnostic, referral- and service-level factors and treatment non-attendance and early treatment cessation were investigated using a series of multivariable generalised estimation equations. Results: There were 1654 suicidal referrals for 1444 people during the study period. Those identified with a risk of suicide were less likely to never attend treatments (16.14% vs 19.77%), but were more likely to disengage earlier from subsequent service sessions (16.02% vs 12.41%), compared to those with no risk of suicide. A higher likelihood of non-attendance to any primary mental health care service sessions was associated with those aged 25–44, lower socioeconomic status, a presentation for substance use and a referral from acute care (either emergency department or hospital). Among those who attended an initial treatment session, younger age (18–24 years) and a longer waiting time for an initial follow-up appointment were associated with a higher likelihood of early treatment cessation from primary mental health care services. Conclusion: These findings can inform potential strategies in routine primary mental health care practice to improve treatment engagement among those at risk of suicidal behaviour. Youth-specific interventions, behavioural engagement strategies and prompt access to services are policy and service priorities.
Characteristics and Management of Children With COVID-19 in a Tertiary Care Hospital in Turkey
Authors: Yayla Burcu Ceylan Cura , Aykac Kubra , Ozsurekci Yasemin , Ceyhan Mehmet 
Published: October 2020

Introduction Limited data are available for pediatric patients with coronavirus disease 2019 (COVID-19), especially with regard to disease management strategies. Objective To assess the children with COVID-19. Method We conducted a retrospective review of the medical records of pediatric patients on March 11 and May 23, 2020. Results We evaluated 77 COVID-19 pediatric patients, of whom 45.5% were male, with a median age of 8 years (interquartile range [IQR] = 2-13), and 6.4% had underlying diseases. Patients were classified according to severity, with the percentages of asymptomatic, mild, moderate, and critical/severe cases determined to be 24.7%, 41.6%, 29.9%, and 3.9%, respectively. Extracorporeal membrane oxygenation and mechanic ventilation were only required for 1 patient. Targeted therapies were used in 3 patients. Conclusion The disease course of COVID-19 appears to be milder in children than in adults, and the treatment course primarily consists of supportive care.
Comparison of changes in albumin binding capacity during hemodiafiltration or hemodialysis with middle cut off membranes
Authors: Koball Sebastian , Westphal Christina , Frimmel Silvius , Hinz Michael , Klammt Sebastian , Mitzner Steffen 
Published: October 2020

Background: Albumin is important for the transport of protein-bound substances (PBS). Albumin binding capacity (ABiC) is reduced in dialysis patients. This can contribute to worsening of uremic symptoms. It is presumed that open-porous middle cut off filters that is, HDx (Baxter-Theranova) remove high molecular substances more efficiently than conventional treatment. To evaluate HDx for the improvement of ABiC and removal of PBS, HDx was compared to hemodiafiltration (Fresenius-FX80, HDF). Methods: We included 32 chronic patients on HDF. After inclusion patients were treated with HDx for 14 days. Blood samples were drawn before/after treatments at study entry, first HDx and sixth HDx, to determine ABiC and other study parameters. Results: ABiC improved in HDx (68.4% vs 72.4%) and HDF (69.9% vs 72.4%) without differences between both therapies. No reduction of albumin concentration during HDx treatment was observed. Conclusion: HDx is accepted as a safe and equally efficient therapy for removing albumin bound uremic toxins compared to HDF with high flux dialyzers.
General and Intensive Care Outcomes for Hospitalized Patients With Solid Organ Transplants With COVID-19
Authors: Mastroianni Fiore , Leisman Daniel E. , Fisler Grace , Narasimhan Mangala 
Published: October 2020

Purpose: COVID-19 has been associated with a dysregulated inflammatory response. Patients who have received solid-organ transplants are more susceptible to infections in general due to the use of immunosuppressants. We investigated factors associated with mechanical ventilation and outcomes in solid-organ transplant recipients with COVID-19. Materials and Methods: We conducted a retrospective cohort study of all solid-organ transplant recipients admitted with a diagnosis of COVID-19 in our 23-hospital health system over a 1-month period. Descriptive statistics were used to describe hospital course and laboratory results and bivariate comparisons were performed on variables to determine differences. Results: Twenty-two patients with solid-organ transplants and COVID-19 were identified. Eight patients were admitted to the ICU, of which 7 were intubated. Admission values of CRP (p = 0.045) and N/L ratio (p = 0.047) were associated with the need for mechanical ventilation. Seven patients (32%) died during admission, including 86% (n = 6) of patients who received mechanical ventilation. Conclusions: In solid-organ transplant recipients with COVID-19, initial CRP and N/L ratio were associated with need for mechanical ventilation.
Acupuncture for metabolic syndrome: systematic review and meta-analysis
Authors: Li Xue , Jia Hong-Xiao , Yin Dong-Qing , Zhang Zhang-Jin 
Published: October 2020

Background: Metabolic syndrome (MetS) is a cluster of conditions associated with an increased risk of cardiovascular disease and diabetes mellitus. Acupuncture may have benefits in the treatment of MetS. This systematic review with meta-analysis aimed to determine the effectiveness and safety of acupuncture therapy in the treatment of MetS. Methods: Large-sample randomized controlled trials (RCTs) of acupuncture treatment for MetS were extracted from multiple Chinese and English databases and analyzed using meta-analysis to evaluate the efficacy/effectiveness of acupuncture with respect to various MetS indices in comparison with control treatments including conventional medications (CMs) and lifestyle intervention (LI), together and separately. Results: A total of 13 RCTs were identified with 423 subjects undergoing acupuncture regimens and 411 receiving control interventions. Active acupuncture yielded better outcomes than sham acupuncture with respect to improving multiple MetS indices. Acupuncture monotherapy had similar effectiveness in controlling triglyceride levels and high-density lipoprotein levels compared to CMs. The overall effects of adjunctive acupuncture were markedly greater than those of controls (CMs + LI, CMs, and LI) with respect to waist circumference with a mean difference of −5.11 cm (Z = 4.57, p < 0.001) and body mass index with a mean difference of −2.54 (Z = 5.38, p <0.001), and improvements were observed in most hyperlipidemia indices and fasting blood glucose. An evidence-based acupuncture regimen was identified as a future treatment strategy for MetS. Conclusion: Acupuncture is beneficial in the treatment of MetS and could serve as an alternative therapy for MetS-associated conditions. Larger-scale RCTs are needed to confirm the efficacy/effectiveness of our recommended evidence-based acupuncture regimen in MetS.
Circulating Tumor Cells Counting Act as a Potential Prognostic Factor in Cervical Cancer
Authors: Du Kunpeng , Huang Qian , Bu Junguo , Zhou Jieling , Huang Zijian , Li Jiqiang 
Published: October 2020

Background: Circulating tumor cells (CTCs) hold huge potential for both clinical applications and basic research into the management of cancer, but the relationship between CTC count and cervical cancer prognosis remains unclear. Therefore, research on this topic is urgently required. Objective: This study investigated whether CTCs were detectable in patients with cervical cancer and whether CTC count was an indicator of prognosis. Methods: We enrolled 107 patients with pathologically confirmed cervical cancer. CTCs were detected after radiotherapy or concurrent cisplatin-containing chemotherapy in all patients. We evaluated all medical records and imaging data as well as follow-up information to calculate progression-free survival (PFS). PFS was defined as the time until first diagnosis of tumor progression or death. We also analyzed the relationship between CTC count and patient age, disease stage, histological differentiation, tumor size, and pathological type. Results: CTCs were identified in 86 of 107 patients (80%), and the CTC count ranged from 0 to 27 cells in 3.2 mL blood. The median progression-free survival (PFS) was 43.1 months. Patients in which CTCs were detected had a significantly shorter PFS than CTC-negative patients (P = 0.018). Multivariate analysis indicated that CTC count was an independent negative prognostic factor for survival. However, no correlation was observed between CTC count and patient age, disease stage, histological differentiation, tumor size, and pathological type. Conclusion: CTC count is an independent negative prognostic factor for cervical cancer.
Short-term effectiveness of medial unicompartmental knee arthroplasty in young patients aged less than or equal to 60 years
Authors: Wang Fangxing , Xue Huaming , Ma Tong , Wen Tao , Yang Tao , Xue Long , Tu Yihui 
Published: October 2020

Purpose: The treatment for young patients with advanced knee arthritis by Oxford unicompartmental knee arthroplasty (Oxford-UKA) is still controversial. A relative few studies were published about Asian patients. We evaluated midterm results of Oxford-UKA in young patients aged less than or equal to 60 years. Methods: Between December 2009 and December 2018, 95 patients (109 knees) (mean age 57.48 years; range: 33–60 years) were included. The mean follow-up period was 3.0 years (range: 1.0–9.5 years). The functional outcomes and pain score of the knee before and after surgery were examined. Results: To the last follow-up, no patient died, six patients (nine knees) were lost and one patient underwent total knee revision in case of unexplained postoperative pain. The patients demonstrated significant improvement in range of knee motion (103.65 vs. 115.96, p < 0.05), Oxford Knee Score (40.0 vs. 14.4, p < 0.05), Hospital for Special Surgery Score (56.0 vs. 85.7, p < 0.05), and Visual Analogue Score (VAS) (5.23 vs. 1.08, p < 0.05) before and after surgery. Conclusion: Our midterm results showed that the Oxford-UKA was a reliable and effective treatment option for young patients aged less than or equal to 60 years with anterior medial osteoarthritis. The knee pain can be effectively relieved and excellent functional activities of the knee joint can be obtained after surgery.
Leukemic evolution of polycythemia vera and essential thrombocythemia: genomic profiles predict time to transformation
Authors: Luque Paz Damien , Jouanneau-Courville Rébecca , Riou Jérémie , Ianotto Jean-Christophe , Boyer Françoise , Chauveau Aurélie , Renard Maxime , Chomel Jean-Claude , Cayssials Emilie , Gallego-Hernanz Maria-Pilar , Pastoret Cédric , Murati Anne , Courtier Frédéric , Rousselet Marie-Christine , Quintin-Roué Isabelle , Cottin Laurane , Orvain Corentin , Thépot Sylvain , Chrétien Jean-Marie , Delneste Yves , Ifrah Norbert , Blanchet Odile , Hunault-Berger Mathilde , Lippert Eric , Ugo Valérie 
Published: October 2020

Abstract
Among myeloproliferative neoplasms, polycythemia vera (PV) and essential thrombocythemia (ET) are the 2 entities associated with the most chronic disease course. Leukemic evolution occurs rarely but has a grim prognosis. The interval between diagnosis and leukemic evolution is highly variable, from a few years to &gt;20 years. We performed a molecular evaluation of 49 leukemic transformations of PV and ET by targeted next-generation sequencing. Using a hierarchical classification, we identified 3 molecular groups associated with a distinct time to leukemic transformation. Short-term transformations were mostly characterized by a complex molecular landscape and mutations in IDH1/2, RUNX1, and U2AF1 genes, whereas long-term transformations were associated with mutations in TP53, NRAS, and BCORL1 genes. Studying paired samples from chronic phase and transformation, we detected some mutations already present during the chronic phase, either with a significant allele burden (short-term transformation) or with a very low allele burden (especially TP53 mutations). However, other mutations were not detected even 1 year before leukemic transformation. Our results suggest that the leukemic transformation of PV and ET may be driven by distinct time-dependent molecular mechanisms.
MLL-TFE3: a novel and aggressive KMT2A fusion identified in infant leukemia
Authors: Kosasih Hansen J. , Davidson Nadia M. , Bjelosevic Stefan , Morrish Emma , Brennan Margs S. , Oshlack Alicia , Johnstone Ricky W. , Brumatti Gabriela , Khaw Seong L. , Ekert Paul G. 
Published: October 2020

Key Points
A novel KMT2A-rearrangement, MLL-TFE3, was identified in an infant leukemia patient. MLL-TFE3 expression produces aggressive leukemia in a mouse model.
Plasma calprotectin was associated with platelet activation and no-reflow phenomenon in acute coronary syndrome
Authors: Song Nian-Peng , Zhen Xiao-Wen , Li Liu-dong , Zhong Lin , Wang Hua , An Yi 
Published: October 2020

Abstract
Background
No-reflow occurs in 3–4% of all percutaneous coronary interventions (PCIs) and has a strong negative impact on clinical outcomes of acute coronary syndrome (ACS). Therefore, the discovery of a biomarker that can early predict the occurrence of no-reflow has great clinical significance. Multiple factors including platelet activation are relevant to no-reflow. Calprotectin is found to be a biomarker of plaque instability and is identified to be a novel diagnostic and prognostic biomarker of cardiovascular diseases. The association of plasma calprotectin with platelet activation and no-reflow phenomenon in ACS is not clear.

Methods
In this prospective study performed at Yantai Yuhuangding Hospital from 2017 to 2018, a total of 176 Chinese patients with ACS who had undergone PCIs were recruited consecutively, aged from 30 to 88 years. Angiographic no-reflow was defined as thrombolysis in myocardial infarction grade less than 3. Blood samples were collected immediately at admission for the detection of plasma calprotectin and platelet–monocyte aggregates formation. Statistical analysis was performed for the variable’s comparisons between groups and the prediction value of plasma calprotectin for no-reflow.

Results
The mean age of the 176 included ACS patients were 64(±11) years and acute ST-segment elevation myocardial infarction (STEMI) was present in 41.5% of patients. Twenty-two patients had no-reflow during the PCI procedures and the prevalence was 12.5%. Patients with higher plasma calprotectin had a higher level of platelet–monocyte aggregates (PMA) and a higher prevalence of no-reflow (p < 0.001). The multivariate regression showed that plasma calprotectin and admission hs-cTnI were independently associated with PMA, while plasma calprotectin and serum LDL-c were independent predictors of no-reflow (p < 0.001 and p = 0.017). AUC of calprotectin for predicting no-reflow were 0.898. The cut-off value of plasma calprotectin for no-reflow was 4748.77 ng/mL with a sensitivity of 0.95 and a specificity of 0.77.

Conclusion
Plasma calprotectin was associated with platelet activation and may act as an early predictive biomarker of no-reflow in patients with acute coronary syndrome.