bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospital admission risk stratification of patients with gout presenting to the emergency department
Authors: Han Wang , Allameen Nur Azizah , Ibrahim Irwani , Dhanasekaran Preeti , Mengling Feng , Lahiri Manjari 
Published: January 2022

Abstract
To characterise gout patients at high risk of hospitalisation and to develop a web-based prognostic model to predict the likelihood of gout-related hospital admissions.
This was a retrospective single-centre study of 1417 patients presenting to the emergency department (ED) with a gout flare between 2015 and 2017 with a 1-year look-back period. The dataset was randomly divided, with 80% forming the derivation and the remaining forming the validation cohort. A multivariable logistic regression model was used to determine the likelihood of hospitalisation from a gout flare in the derivation cohort. The coefficients for the variables with statistically significant adjusted odds ratios were used for the development of a web-based hospitalisation risk estimator. The performance of this risk estimator model was assessed via the area under the receiver operating characteristic curve (AUROC), calibration plot, and brier score. Patients who were hospitalised with gout tended to be older, less likely male, more likely to have had a previous hospital stay with an inpatient primary diagnosis of gout, or a previous ED visit for gout, less likely to have been prescribed standby acute gout therapy, and had a significant burden of comorbidities. In the multivariable-adjusted analyses, previous hospitalisation for gout was associated with the highest odds of gout-related admission. Early identification of patients with a high likelihood of gout-related hospitalisation using our web-based validated risk estimator model may assist to target resources to the highest risk individuals, reducing the frequency of gout-related admissions and improving the overall health-related quality of life in the long term.

Key points

• We reported the characteristics of gout patients visiting a tertiary hospital in Singapore.
• We developed a web-based prognostic model with non-invasive variables to predict the likelihood of gout-relatedhospital admissions.
Effect of dose adjustments on the efficacy and safety of tofacitinib in patients with rheumatoid arthritis: a post hoc analysis of an open-label, long-term extension study (ORAL Sequel)
Authors: Mueller Ruediger B. , Schulze-Koops Hendrik , Furst Daniel E. , Cohen Stanley B.  , Kwok Kenneth , Wang Lisy , Killeen Tim , von Kempis Johannes 
Published: January 2022

Abstract
Introduction/objectives
We assess the impact of switching versus staying on the same tofacitinib dose on efficacy and safety in patients with rheumatoid arthritis (RA).

Methods
ORAL Sequel was an open-label, long-term extension study of patients with RA receiving tofacitinib 5 or 10 mg BID for up to 9.5 years. Tofacitinib doses could be switched during the study at investigator discretion. In this post hoc analysis, data from ORAL Sequel were stratified into four groups: 5 → 10 mg BID (Dose-up); 5 mg BID (Stay-on 5); 10 → 5 mg BID (Dose-down); and 10 mg BID (Stay-on 10). Efficacy assessments over 12 months included: change from baseline in 4-component Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28), and DAS28 minimum clinically important difference, remission, and low disease activity (LDA) rates. Safety was assessed for the study duration.

Results
Generally, DAS28 improvements and minimum clinically important difference rates were significantly greater (p < 0.05) in Dose-up versus Stay-on 5 up to month 12. DAS28 remission rates were significantly greater in Dose-up versus Stay-on 5 at month 12. Change from baseline in DAS28 was similar in Dose-down and Stay-on 10. No significant differences in DAS28 LDA rates were observed between groups. Safety data were similar overall across the four groups.

Conclusion
In patients with RA receiving open-label tofacitinib, this analysis found that some benefited from increasing dose from 5 to 10 mg BID and did not find that reducing dose from 10 to 5 mg BID affected efficacy or that dose switching in either direction affected safety.

Study registration
ClinicalTrials.gov number NCT00413699. Registered December 20, 2006. https://clinicaltrials.gov/ct2/show/NCT00413699

Key Points• This post hoc analysis of data from the long-term extension study, ORAL Sequel, assessed the impact of dose switching between tofacitinib 5 and 10 mg twice daily (BID), at the investigator’s discretion, on efficacy and safety in patients with rheumatoid arthritis (RA).• Dosing up from tofacitinib 5 to 10 mg BID was associated with improved efficacy up to 12 months versus staying on 5 mg BID, and dosing down from 10 to 5 mg BID was not generally associated with a significant loss of efficacy.• Safety outcomes were generally consistent across dose groups and did not change markedly after switching dose in either direction.• These findings can help to inform physicians on what may be expected in terms of efficacy and safety when adjusting tofacitinib dose according to clinical need. The recommended tofacitinib dosage for the treatment of RA in most jurisdictions is 5 mg BID.
Avelumab first-line maintenance plus best supportive care (BSC) vs BSC alone for advanced urothelial carcinoma: JAVELIN Bladder 100 Japanese subgroup analysis
Authors: Tomita Yoshihiko , Yamamoto Yoshiaki , Tsuchiya Norihiko , Kanayama Hiroomi , Eto Masatoshi , Miyake Hideaki , Powles Thomas , Yoshida Mizuki , Koide Yuichiro , Umeyama Yoshiko , di Pietro Alessandra , Uemura Hirotsugu 
Published: January 2022

Abstract
Background
The phase 3 JAVELIN Bladder 100 trial showed significantly prolonged overall survival (OS) with avelumab as first-line (1L) maintenance therapy + best supportive care (BSC) vs BSC alone in patients with advanced urothelial carcinoma (UC) that had not progressed with 1L platinum-containing chemotherapy. Efficacy and safety were assessed in patients enrolled in Japan.

Methods
Patients with locally advanced or metastatic UC that had not progressed with 4–6 cycles of 1L platinum-containing chemotherapy were randomized to avelumab (10 mg/kg intravenously every 2 weeks) + BSC or BSC alone. The primary endpoint was OS, and secondary endpoints included progression-free survival (PFS) and safety.

Results
In Japanese patients (n = 73) randomized to avelumab + BSC (n = 36) or BSC alone (n = 37), median OS was 24.7 months (95% CI, 18.2-not estimable) vs 18.7 months (95% CI, 12.8–33.0), respectively (HR, 0.81 [95% CI, 0.41–1.58]), and median PFS was 5.6 months (95% CI, 1.9–9.4) vs 1.9 months (95% CI, 1.9–3.8), respectively (HR, 0.63 [95% CI, 0.36–1.11]). In the avelumab + BSC and BSC-alone arms, grade ≥ 3 treatment-emergent adverse events (AEs) occurred in 50.0% vs 8.1%, including grade ≥ 3 treatment-related AEs in 13.9% vs 0%, respectively. Efficacy and safety results in Japanese patients were generally consistent with findings in the overall trial population.

Conclusion
Avelumab 1L maintenance treatment showed a favorable benefit-risk balance in Japanese patients, supporting avelumab 1L maintenance as a new standard of care in Japanese patients with advanced UC that has not progressed with 1L platinum-containing chemotherapy.

Trial registration
Clinicaltrials.gov NCT02603432.
Validation of the estimated glomerular filtration rate equation for Japanese children younger than 2 years
Authors: Gotoh Yoshimitsu , Uemura Osamu , Fujita Naoya , Hamasaki Yuko , Honda Masataka , Ishikura Kenji ,   On behalf of the Pediatric CKD Study Group in Japan in conjunction with the Committee of Measures for Pediatric CKD of the Japanese Society of Pediatric Nephrology, Gotoh Yoshimitsu , Uemura Osamu , Fujita Naoya , Hamasaki Yuko , Honda Masataka , Ishikura Kenji 
Published: January 2022

Abstract
Background
We have developed a simple and easy method of estimating the glomerular filtration rate (eGFR) of serum creatinine in Japanese children (eGFRUemura). The eGFR equation is for children aged 2–18 years. Therefore Uemura et al. developed an equation for children younger than 2 years (eGFRunder 2). The aim of the present study was to validate this new equation.

Methods
We collected the data of 13 patients from previous studies and compared the results of eGFRunder 2, eGFRUemura, and updated eGFR developed by Schwartz (eGFRSchwartz) with measured GFR using mean error (ME), root mean square error (RMSE), P30 and Bland–Altman analysis.

Results
The ME of eGFRunder 2, eGFRUemura and eGFRSchwartz were 2.3 ± 15.9, 7.7 ± 14.5, and 16.0 ± 18.2 ml/min/1.73m2, respectively. The RMSEs were 15.5, 15.9, and 49.6, respectively. The P30 values were 76.9%, 76.9%, and 53.8%, respectively. The graph of Bland–Altman bias analysis showed fan-shape. The eGFRunder 2 equation was the most accurate in the three equations.

Conclusion
The eGFRunder 2 equation was useful for Japanese children younger than 2 years.
Aboveground biomass increments over 26 years (1993–2019) in an old-growth cool-temperate forest in northern Japan
Authors: Noguchi Mahoko , Hoshizaki Kazuhiko , Matsushita Michinari , Sugiura Daiki , Yagihashi Tsutomu , Saitoh Tomoyuki , Itabashi Tomohiro , Kazuhide Ohta , Shibata Mitsue , Hoshino Daisuke , Masaki Takashi , Osumi Katsuhiro , Takahashi Kazunori , Suzuki Wajirou 
Published: January 2022

AbstractAssessing long-term changes in the biomass of old-growth forests with consideration of climate effects is essential for understanding forest ecosystem functions under a changing climate. Long-term biomass changes are the result of accumulated short-term changes, which can be affected by endogenous processes such as gap filling in small-scale canopy openings. Here, we used 26 years (1993–2019) of repeated tree census data in an old-growth, cool-temperate, mixed deciduous forest that contains three topographic units (riparian, denuded slope, and terrace) in northern Japan to document decadal changes in aboveground biomass (AGB) and their processes in relation to endogenous processes and climatic factors. AGB increased steadily over the 26 years in all topographic units, but different tree species contributed to the increase among the topographic units. AGB gain within each topographic unit exceeded AGB loss via tree mortality in most of the measurement periods despite substantial temporal variation in AGB loss. At the local scale, variations in AGB gain were partially explained by compensating growth of trees around canopy gaps. Climate affected the local-scale AGB gain: the gain was larger in the measurement periods with higher mean air temperature during the current summer but smaller in those with higher mean air temperature during the previous autumn, synchronously in all topographic units. The influences of decadal summer and autumn warming on AGB growth appeared to be counteracting, suggesting that the observed steady AGB increase in KRRF is not fully explained by the warming. Future studies should consider global and regional environmental factors such as elevated CO2 concentrations and nitrogen deposition, and include cool-temperate forests with a broader temperature range to improve our understanding on biomass accumulation in this type of forests under climate change.
Transgenic plants expressing immunosuppressive dsRNA improve entomopathogen efficacy against Spodoptera littoralis larvae
Authors: Di Lelio Ilaria , Barra Eleonora , Coppola Mariangela , Corrado Giandomenico , Rao Rosa , Caccia Silvia 
Published: January 2022

AbstractTransgenic plants that express double-stranded RNA (dsRNA) targeting vital insect genes have recently emerged as a valuable new tool for pest control. In this study, tobacco plants were transformed to produce dsRNA targeting Sl 102 gene that is involved in the immune response of Spodoptera littoralis larvae, a serious lepidopteran pest of several crops. Experimental larvae reared on transgenic tobacco lines showed (1) a strongly reduced level of Sl 102 transcripts, which was positively associated with food consumption; (2) a substantial impairment of the encapsulation response mediated by hemocytes; and (3) a marked increase in the susceptibility to Xentari™, a Bacillus thuringiensis-based insecticide. Importantly, this approach may allow a reduction in the doses of B. thuringiensis used for field applications and enhance its killing activity on mature larvae. The results obtained thus support the use of immunosuppressive RNAi plants to enhance the performance of microbial insecticides on lepidopteran larvae.
Silvopastoral and conventional management of extensive livestock and the diversity of bats in fragments of tropical dry forest in Córdoba, Colombia
Authors: Ballesteros-Correa Jesús , Pérez-Torres Jairo 
Published: January 2022

AbstractThe establishment of extensive livestock systems in the Colombian Caribbean Region has historically generated a strong loss of the tropical dry forest (TDF) with negative effects on biodiversity. Currently, the implementation of silvopastoral systems (SPS) has been proposed with strategy to curb the loss of biodiversity caused by the conventional management system (CS). The objective was to evaluate the effect of SPS and CS of extensive livestock on the assemblage of bats associated with fragments of TDF. During a continuous year and a sampling effort of 30,240 h-net/night, the structure and composition of bat assemblage between SPS and CS were compared. 2788 bats belonging to six families, 23 genera, and 39 species were captured. ThePhyllostomidaefamily presented the highest species richness (S = 30), with the greatest abundance in theStenodermatinaesubfamily (n = 1543). Bat assemblage in the SPS fragments was more equitable; and the relative abundance per species, per genera, and per foraging guilds was also significantly higher. The capture success showed significant variations between the climatic seasons (dry and rainy). The rate of species turnover was higher in the CS fragments. The speciesArtibeus planirostris, Artibeus lituratus, Carollia perspicillata, Carollia castanea, Phyllostomus discolor, Dermanura phaeotis, Uroderma convexum, Glossophaga soricina, C. brevicauda,andSturnira liliumaccounted for 92% of the captures. In conclusion, frugivorous bats were more abundant in the SPS, type of extensive livestock management that can generate greater temporal stability of bat assemblage. This research provides the first scientific evidence of the positive effect of silvopastoral management on the diversity of bats in tropical dry forest areas of the Colombian Caribbean region.
Multiple graph fusion based on Riemannian geometry for motor imagery classification
Authors: Xie Xiaofeng , Zou Xiaokun , Yu Tianyou , Tang Rongnian , Hou Yao , Qi Feifei 
Published: January 2022

AbstractIn motor imagery-based brain-computer interfaces (BCIs), the spatial covariance features of electroencephalography (EEG) signals that lie on Riemannian manifolds are used to enhance the classification performance of motor imagery BCIs. However, the problem of subject-specific bandpass frequency selection frequently arises in Riemannian manifold-based methods. In this study, we propose a multiple Riemannian graph fusion (MRGF) model to optimize the subject-specific frequency band for a Riemannian manifold. After constructing multiple Riemannian graphs corresponding to multiple bandpass frequency bands, graph embedding based on bilinear mapping and graph fusion based on mutual information were applied to simultaneously extract the spatial and spectral features of the EEG signals from Riemannian graphs. Furthermore, with a support vector machine (SVM) classifier performed on learned features, we obtained an efficient algorithm, which achieves higher classification performance on various datasets, such as BCI competition IIa and in-house BCI datasets. The proposed methods can also be used in other classification problems with sample data in the form of covariance matrices.
Interaction Between Waves and Turbulence Within the Nocturnal Boundary Layer
Authors: Barbano Francesco , Brogno Luigi , Tampieri Francesco , Di Sabatino Silvana 
Published: January 2022

AbstractThe presence of waves is proven to be ubiquitous within nocturnal stable boundary layers over complex terrain, where turbulence is in a continuous, although weak, state of activity. The typical approach based on Reynolds decomposition is unable to disaggregate waves from turbulence contributions, thus hiding any information about the production/destruction of turbulence energy injected/subtracted by the wave motion. We adopt a triple-decomposition approach to disaggregate the mean, wave, and turbulence contributions within near-surface boundary-layer flows, with the aim of unveiling the role of wave motion as a source and/or sink of turbulence kinetic and potential energies in the respective explicit budgets. By exploring the balance between buoyancy (driving waves) and shear (driving turbulence), a simple interpretation paradigm is introduced to distinguish two layers, namely the near-ground and far-ground sublayer, estimating where the turbulence kinetic energy can significantly feed or be fed by the wave. To prove this paradigm, a nocturnal valley flow is used as a case study to detail the role of wave motions on the kinetic and potential energy budgets within the two sublayers. From this dataset, the explicit kinetic and potential energy budgets are calculated, relying on a variance–covariance analysis to further comprehend the balance of energy production/destruction in each sublayer. With this investigation, we propose a simple interpretation scheme to capture and interpret the extent of the complex interaction between waves and turbulence in nocturnal stable boundary layers.
The Selective NLRP3-inflammasome inhibitor MCC950 Mitigates Post-resuscitation Myocardial Dysfunction and Improves Survival in a Rat Model of Cardiac Arrest and Resuscitation
Authors: Zheng Guanghui , He Fenglian , Xu Jing , Hu Juntao , Ge Weiwei , Ji Xianfei , Wang Changsheng , Bradley Jennifer L. , Peberdy Mary Ann , Ornato Joseph P. , Jiang Longyuan , Toldo Stefano , Wang Tong , Tang Wanchun 
Published: January 2022

Abstract
Purpose
To investigate the effects of the selective NLRP3 inflammasome inhibitor MCC950 on post-resuscitation myocardial function and survival in a rat model of cardiopulmonary resuscitation (CPR).

Methods
Thirty-six Sprague Dawley rats were randomized into three groups: (1) MCC950, (2) control, and (3) sham. Each group consisted of a 6 h non-survival subgroup (n = 6) and a 48 h survival subgroup (n = 6). Ventricular fibrillation (VF) was induced and untreated for 6 min. CPR was initiated and continued for 8 min. Resuscitation was attempted with a 4 J defibrillation. MCC950 (10 mg/kg) or vehicle was administered via intraperitoneal injection immediately after the return of spontaneous circulation (ROSC). Myocardial function and sublingual microcirculation were measured after ROSC in the non-survival subgroups. Plasma levels of interleukin Iβ (IL-1β) and cardiac troponin I (cTnI) were measured at baseline and 6 h in the non-survival subgroups. Heart tissue was harvested to measure the NLRP3 inflammasome constituents, including NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, and IL-1β. Survival duration and neurologic deficit score (NDS) were recorded and evaluated among survival groups.

Results
Post-resuscitation myocardial function and sublingual microcirculation were improved in MCC950 compared with control (p < 0.05). IL-1β and cTnI were decreased in MCC950 compared to control (p < 0.01). The MCC950 treated groups showed significantly reduced ASC, caspase-1, and IL-1β compared with the control group (p < 0.05). Survival at 48 h after ROSC was greater in MCC950 (p < 0.05) with improved NDS (p < 0.05).

Conclusion
Administration of MCC950 following ROSC mitigates post-resuscitation myocardial dysfunction and improves survival.
Genome-wide DNA methylome and transcriptome changes induced by inorganic nanoparticles in human kidney cells after chronic exposure
Authors: Soltysova Andrea , Begerova Patricia , Jakic Kristina , Kozics Katarina , Sramkova Monika , Meese Eckart , Smolkova Bozena , Gabelova Alena 
Published: January 2022

AbstractThe unique physicochemical properties make inorganic nanoparticles (INPs) an exciting tool in diagnosis and disease management. However, as INPs are relatively difficult to fully degrade and excrete, their unintended accumulation in the tissue might result in adverse health effects. Herein, we provide a methylome–transcriptome framework for chronic effects of INPs, commonly used in biomedical applications, in human kidney TH-1 cells. Renal clearance is one of the most important routes of nanoparticle excretion; therefore, a detailed evaluation of nanoparticle-mediated nephrotoxicity is an important task. Integrated analysis of methylome and transcriptome changes induced by INPs (PEG-AuNPs, Fe3O4NPs, SiO2NPs, and TiO2NPs) revealed significantly deregulated genes with functional classification in immune response, DNA damage, and cancer-related pathways. Although most deregulated genes were unique to individual INPs, a relatively high proportion of them encoded the transcription factors. Interestingly, FOS hypermethylation inversely correlating with gene expression was associated with all INPs exposures. Our study emphasizes the need for a more comprehensive investigation of INPs’ biological safety, especially after chronic exposure.
Graphical abstract
ERK inhibitor ASN007 effectively overcomes acquired resistance to EGFR inhibitor in non‐small cell lung cancer
Authors: Ku Bo Mi , Heo Jae Yeong , Kim Jinchul , sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Park Keunchil , Ahn Myung-Ju 
Published: January 2022

SummaryThe emergence of acquired resistance limits the long-term efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs). Thus, development of effective strategies to overcome resistance to EGFR TKI is urgently needed. Multiple mechanisms to reactivate ERK signaling have been successfully demonstrated in acquired resistance models. We found that in EGFR mutant non-small cell lung cancer (NSCLC) patients, acquired resistance to EGFR TKIs was accompanied by increased activation of ERK. Increased ERK activation was also found in in vitro models of acquired EGFR TKI resistance. ASN007 is a potent selective ERK1/2 inhibitor with promising antitumor activity in cancers with BRAF and RAS mutations. ASN007 treatment impeded tumor cell growth and the cell cycle in EGFR TKI-resistant cells. In addition, combination treatment with ASN007 and EGFR TKIs significantly decreased the survival of resistant cells, enhanced induction of apoptosis, and effectively inhibited the growth of erlotinib-resistant xenografts, providing the preclinical rationale for testing combinations of ASN007 and EGFR TKIs in EGFR-mutated NSCLC patients. This study emphasizes the importance of targeting ERK signaling in maintaining the long-term benefits of EGFR TKIs by overcoming acquired resistance.