bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caffeine Consumption and Dementia: Are Lewy Bodies the Link?
Authors: Cornelis Marilyn C. , Bennett David A. , Weintraub Sandra , Schneider Julie A. , Morris Martha Clare 
Published: March 2022

ObjectiveThe objective of this study was to examine the association between caffeine intake and cognitive impairment. Caffeine‐neuropathology correlations and interactions with lifestyle and genetic factors impacting caffeine metabolism and response were also tested.MethodsWe included 888 participants aged 59+ years from the Rush Memory and Aging Project (MAP) and 303,887 participants aged 55+ years from the UK Biobank (UKB). MAP participants took part in annual cognitive testing. Diagnosis of dementia was based on clinical neurological examination and standardized criteria. A subset provided postmortem tissue for neuropathologic evaluation for common age‐related diseases (eg, Alzheimer's disease [AD], Lewy bodies, and vascular). For UKB, dementia was determined by linked hospital and death records. Self‐reported caffeine intake was estimated using food‐frequency questionnaires in both cohorts. Cox proportional hazard ratio (HR), regression, and mixed models were used to examine associations of caffeine intake with incident dementia, cognitive decline, and neuropathology.ResultsIn MAP, compared to ≤100 mg/day, caffeine intake >100 mg/day was associated with a significantly higher HR (95% confidence interval [CI]) of all‐cause (HR = 1.35, 95% CI = 1.03–1.76) and AD (HR = 1.41, 95% CI = 1.07–1.85) dementia. Caffeine intake was not associated with cognitive decline. In UKB, compared to ≤100 mg/day, the HRs (95% CI) of all‐cause dementia for consuming 100 ≤ 200, 200 ≤ 300, 300 ≤ 400, and > 400 mg/day were 0.83 (95% CI = 0.72–0.94), 0.74 (95% CI = 0.64–0.85), 0.74 (95% CI = 0.64–0.85), and 0.92 (95% CI = 0.79–1.08), respectively. Similar results were observed for Alzheimer's dementia. In MAP, caffeine intake was inversely associated with postmortem Lewy bodies but no other age‐related pathologies. Caffeine intake >100 mg/day was associated with lower neocortical type Lewy bodies (odds ratio (95%CI): 0.40 (95% CI = 0.21–0.75).InterpretationCaffeine intake was inconsistently associated with clinical dementia; potentially explained by cohort differences in underlying dementia etiology. Lewy bodies may link caffeine to lower risk in some persons. ANN NEUROL 2022;91:834–846
Occurrence and population structure of sharks in two ecologically or biologically significant marine areas off north‐eastern Brazil
Authors: Barcellos Laís R. , Barreto Rodrigo , Lessa Rosângela PT 
Published: March 2022

Abstract

Ecologically or Biologically Significant Marine Areas (EBSAs) are rare, and highly important sites to the life history of a number of declining shark species are endangered by fishing.
The high diversity of sharks caught by fisheries is difficult to monitor due to the scarcity of information on species‐specific biological aspects (growth, maturity and fertility rate).
There are two EBSAs off north‐eastern Brazil, where key species are caught, more specifically the oceanic whitetip (Carcharhinus longimanus), mako (Isurus oxyrinchus), blue (Prionace glauca) and silky (Carcharhinus falciformis) sharks. Another 23 species displaying low frequency in catches have also been recorded, many of them considered threatened according to the IUCN Red List and the Brazilian Ministry of Environment.
The main purpose of this study was to generate information about shark diversity and demonstrate the role of the two EBSAs in their conservation. After analysing fishing data collected from 2000 to 2011, maps were built to categorize shark species by phases of their ontogenetic development (neonate, young and adult) based on samples of C. falciformis (n = 330), C. longimanus (n = 440), I. oxyrinchus (n = 452) and P. glauca (n = 8,176).
Shark stocks comprised mainly juveniles, which raises concerns since they are considered a crucial life stage for the sustainability of shark populations. Catch monitoring also highlighted that several of the species caught are threatened and their catch is either prohibited or limited according to the Brazilian laws and international rules in place.
Action plans and enforcement of laws and rules are needed to deliver the protective measures needed for shark species in these EBSAs.
A Comparison of International League of Associations for Rheumatology and Pediatric Rheumatology International Trials Organization Classification Systems for Juvenile Idiopathic Arthritis Among Children in a Canadian Arthritis Cohort
Authors: Lee Jennifer J. Y. , Eng Simon W. M. , Guzman Jaime , Duffy Ciáran M. , Tucker Lori B. , Oen Kiem , Yeung Rae S. M. , Feldman Brian M. ,   the ReACCh‐Out Investigators
Published: March 2022

ObjectiveThe aim of the Paediatric Rheumatology International Trials Organisation (PRINTO) juvenile idiopathic arthritis (JIA) classification criteria, which is still in development, is to identify homogeneous groups of JIA patients. This study was undertaken to compare International League of Associations for Rheumatology (ILAR) JIA classification criteria and PRINTO JIA classification criteria using data from the ReACCh‐Out (Research in Arthritis in Canadian Children, Emphasizing Outcomes) cohort.MethodsWe used clinicobiologic data recorded within 7 months of diagnosis to assign a diagnosis of JIA and identify subcategories of JIA among 1,228 patients according to the 2 JIA classification systems. We compared the proportions of patients classified and the alignment of classification categories with clinicobiologic subtypes and adult arthritis types.ResultsThe PRINTO criteria classified 244 patients (19.9%) as having early‐onset antinuclear antibody–positive JIA, 157 (12.8%) as having enthesitis/spondylitis–related JIA, 38 (3.1%) as having systemic JIA, and 10 (0.8%) as having rheumatoid factor–positive JIA. A total of 12% of patients were unclassifiable using the ILAR criteria, while 63.3% were unclassifiable using the PRINTO criteria (777 with other JIA and 2 with unclassified JIA). In sensitivity analyses, >50% of patients remained unclassifiable using the PRINTO criteria. Compared to the PRINTO criteria, ILAR JIA categories aligned better with clinicobiologic subtypes in 131 patients (χ2 = 44, P = 0.005, versus χ2 = 15, P = 0.07 for PRINTO), and ILAR categories aligned better with adult types of arthritis in 389 evaluable patients.ConclusionCurrently identified PRINTO disorders can only be used to classify a minority of JIA patients, leaving a large proportion of JIA patients with other disorders requiring further characterization. Current PRINTO JIA classification criteria do not align better with clinicobiologic subtypes or adult forms of arthritis compared with the older ILAR classification system.
Designing for serendipity in online knowledge communities: An investigation of tag presentation formats and openness to experience
Authors: Qin Chunxiu , Liu Yaxi , Ma Xubu , Chen Jiangping , Liang Huigang 
Published: March 2022

AbstractUsers increasingly acquire, share, and create knowledge in online knowledge communities, making them massive dynamic knowledge repositories that spark inspiration. While online knowledge communities provide powerful searching tools, they ignore the potential of serendipity in fostering knowledge acquisition. Against this backdrop, this research investigates whether serendipity can be stimulated by design features of communities. Specifically, we examine whether different tag presentation formats may promote serendipity. Two hundred seven participants were randomly assigned to our experimental website that displays one of three tag formats. Results show that users experienced serendipity more frequently while using tag trees than tag clouds, followed by tag lists. Moreover, tag formats moderate how openness to experience affects serendipity. Although openness did not influence serendipity across tag formats, further analysis shows that it significantly decreases serendipity for tag lists, but significantly increases serendipity for tag clouds and trees. Theoretically, these results provide an in‐depth understanding of serendipity that is contingent on the interaction between community design features and personality (e.g., openness to experience). Practically, these findings demonstrate how interface features (e.g., tag presentation formats) facilitate serendipity, thus informing better design of online knowledge communities to improve the efficiency of knowledge acquisition.
Electrochemical Study of Prussian White Cathodes with Glymes – Pathway to Graphite‐Based Sodium‐Ion Battery Full Cells
Authors: Gourang Patnaik Sai , Escher Ines , Ferrero Guillermo A. , Adelhelm Philipp 
Published: March 2022

AbstractPrussian white (PW) cathodes exhibit extremely fast rate kinetics for sodium ion (Na+) insertion/de‐insertion at relatively high potentials. However, one of the major bottlenecks is to pair them with appropriate anode materials having similar rate kinetics. Herein, the combination of graphite anodes and several glyme‐based electrolytes as appropriate building blocks for PW cathodes to achieve high power density without compromising on energy density is reported. Low defect, Na‐rich PW is synthesized, and its electrochemical behavior is studied with conventional carbonate‐based electrolytes as well as with diglyme (2G), tetraglyme (4G) and a 1 : 1 mixture of 2G and 4G. The stability of the electrolytes is also monitored via in situ (operando) pressure cell measurements. Graphite | electrolyte | PW cells are then studied in both two and three electrode configurations. It was found that glymes are compatible with the graphite/PW electrode pair and the resulting cells exhibit very good cyclability and rate capability.
A novel human stem cell‐based biomarker assay for in vitro assessment of developmental toxicity
Authors: Jamalpoor Amer , Hartvelt Sabine , Dimopoulou Myrto , Zwetsloot Tom , Brandsma Inger , Racz Peter I. , Osterlund Torben , Hendriks Giel 
Published: March 2022

AbstractBackgroundTesting for developmental toxicity according to the current regulatory guidelines requires large numbers of animals, making these tests very resource intensive, time‐consuming, and ethically debatable. Over the past decades, several alternative in vitro assays have been developed, but these often suffered from low predictability and the inability to provide a mechanistic understanding of developmental toxicity.MethodsTo identify embryotoxic compounds, we developed a human induced pluripotent stem cells (hiPSCs)‐based biomarker assay. The assay is based on the differentiation of hiPSCs into functional cardiomyocytes and hepatocytes. Proper stem cell differentiation is investigated by morphological profiling and assessment of time‐dependent expression patterns of cell‐specific biomarkers. In this system, a decrease in the expression of the biomarker genes and morphology disruption of the differentiated cells following compound treatment indicated teratogenicity.ResultsThe hiPSCs‐based biomarker assay was validated with 21 well‐established in vivo animal teratogenic and non‐teratogenic compounds during cardiomyocyte and hepatocyte differentiation. The in vivo teratogenic compounds (e.g., thalidomide and valproic acid) markedly disrupted morphology, functionality, and the expression pattern of the biomarker genes in either one or both cell types. Non‐teratogenic chemicals generally had no effect on the morphology of differentiated cells, nor on the expression of the biomarker genes. Compared to the in vivo classification, the assay achieved high accuracy (91%), sensitivity (91%), and specificity (90%).ConclusionThe assay, which we named ReproTracker®, is a state‐of‐the‐art in vitro method that can identify the teratogenicity potential of new pharmaceuticals and chemicals and signify the outcome of in vivo test systems.
Evaluating mental workload during multitasking in simulated flight
Authors: Li Wenbin , Li Rong , Xie Xiaoping , Chang Yaoming 
Published: March 2022

AbstractBackgroundPilots must process multiple streams of information simultaneously. Mental workload is one of the main issues in man–machine interactive mode when dealing with multiple tasks. This study aimed to combine functional near‐infrared spectroscopy (fNIRS) and electrocardiogram (ECG) to detect changes in mental workload during multitasking in a simulated flight.MethodsTwenty‐six participants performed three multitasking tasks at different mental workload levels. These mental workload levels were set by varying the number of subtasks. fNIRS and ECG signals were recorded during tasks. Participants filled in the national aeronautics and space administration task load index (NASA‐TLX) scale after each task. The effects of mental workload on scores of NASA‐TLX, performance of tasks, heart rate (HR), heart rate variability (HRV), and the prefrontal cortex (PFC) activation were analyzed.ResultsCompared to multitasking in lower mental workload conditions, participants exhibited higher scores of NASA‐TLX, HR, and PFC activation when multitasking in high mental workload conditions. Their performance was worse during the high mental workload multitasking condition, as evidenced by the higher average tracking distance, smaller number of response times, and longer response time of the meter. The standard deviation of the RR intervals (SDNN) was negatively correlated with subjective mental workload in the low task load condition and PFC activation was positively correlated with HR and subjective mental workload in the medium task load condition.ConclusionHR and PFC activation can be used to detect changes in mental workload during simulated flight multitasking tasks.
Prolonged progression‐free survival achieved by octreotide LAR plus transarterial embolization in low‐to‐intermediate grade neuroendocrine tumor liver metastases with high hepatic tumor burden
Authors: Liu Yiming , Liu Haikuan , Chen Wenchuan , Yu Hang , Yao Wang , Fan Wenzhe , Li Jiaping , Chen Minhu , Chen Jie , Wang Yu 
Published: March 2022

AbstractObjectiveTo evaluate the efficacy and outcome of transarterial embolization (TAE) plus octreotide long‐acting repeatable (LAR) on patients with low‐to‐intermediate neuroendocrine tumor liver metastases (NETLM).MethodsOne hundred and sixteen patients with G1/G2 NETLM treated with TAE plus octreotide LAR at the First Affiliated Hospital, Sun Yat‐sen University between January 12, 2016 and September 24, 2020 were reviewed. Radiological response was evaluated according to response evaluation criterion in solid tumor version 1.1. Overall progression‐free survival (PFS) was assessed. Intrahepatic and extrahepatic PFS were evaluated in the whole cohort and in patients with the extrahepatic disease (EHD), respectively. Factors affecting treatment response and overall PFS were analyzed using the logistic regression model and Cox proportional hazard model. Adverse events were recorded and evaluated according to Common Terminology Criteria for Adverse Events 5.0.ResultsThe median overall PFS of the whole cohort was 13.6 months. For the patients with EHD, the median intrahepatic PFS and extrahepatic PFS were 13.6 and 26.1 months, respectively. The median overall PFS of patients with hepatic tumor burden (HTB) <10%, 10%–25%, 25%–50%, and >50% were 25.2, 13.6, 11.2, and 12.3 months, respectively. Ki67 >10%, HTB >50%, and bone metastasis were independently associated with overall PFS. The objective response rate was 78.4%. In patients with HTB 25%–50% and >50%, responders (complete response or partial response) had significant prolonged PFS compared with nonresponders (stable disease or progression disease). Ki67 >10%, bone metastasis, and clear tumor margin were independently associated with response to TAE. The most frequent adverse events that occurred after TAE were postembolization syndrome, and no treatment‐associated death occurred during the perioperative period.ConclusionTransarterial embolization plus octreotide LAR can significantly prolong the PFS of neuroendocrine tumor liver metastases, especially with high HTB over 50%. Selected patients with HTB >25% (ki67 ≤10%, absence of bone metastasis, clear tumor margin) could derive prognostic advantage from the combined treatment.
Serum tumor markers level and their predictive values for solid and micropapillary components in lung adenocarcinoma
Authors: Li Zhihua , Wu Weibing , Pan Xianglong , Li Fang , Zhu Quan , He Zhicheng , Chen Liang 
Published: March 2022

AbstractBackgroundThis study aims to reveal the serum tumor marker (STM) levels in lung adenocarcinoma (LUAD) histological subtypes and evaluate their values in predicting the solid and micropapillary components (SMC).MethodsWe retrospectively analyzed 3100 invasive LUAD patients between January 2017 and December 2020. Associations between preoperative STMs (CEA, CYFRA21‐1, CA199, CA724, NSE, AFP) and LUAD subtypes were evaluated. Multivariate regression analyses were used to determine the independent predictors. Predictive models for SMC were constructed and AUC (area under the curve) was calculated.ResultsCEA and CYFRA21‐1 levels differed across the LUAD histological subtypes, with the SPA (solid‐predominant adenocarcinoma) having the highest level and the LPA (lepidic‐predominant adenocarcinoma) harboring the lowest level (p <0.001). Tumors with SMC also had higher CEA and CYFRA21‐1 levels than those absence of SMC. Gender, tumor size, CEA, Ki‐67, EGFR mutation (solid components only), and tumor differentiation were significantly independently associated with the containing of SMC. Patients were split into two data sets (training set: 2017–2019 and validation set: 2020). The model with gender and tumor size yielded an AUC of 0.723 (training set) and 0.704 (validation set) for the solid component. Combination of CEA, gender, and tumor size led to a significant increase in the predictive accuracy (training set: 0.771, p = 0.009; validation set: 0.747, p = 0.034). The AUC of the model for micropapillary component with only gender and tumor size was 0.699 and 0.711 in the training set and validation set, respectively. Integration of CEA with gender and tumor size significantly improved the predictive performance with an AUC of 0.746 (training set, p = 0.045) and 0.753 (validation set, p <0.001).ConclusionSerum CEA and CYFRA21‐1 varied considerably according to LUAD histological subtypes. The combination of serum CEA and other factors showed prominent values in predicting the SMC.
Molecular profile of pure squamous cell carcinoma of the bladder identifies major roles for OSMR and YAP signalling
Authors: Hurst Carolyn D , Cheng Guo , Platt Fiona M , Alder Olivia , Black Emma VI , Burns Julie E , Brown Joanne , Jain Sunjay , Roulson Jo‐An , Knowles Margaret A 
Published: March 2022

AbstractPure squamous cell carcinoma (SCC) is the most common pure variant form of bladder cancer, found in 2–5% of cases. It often presents late and is unresponsive to cisplatin‐based chemotherapy. The molecular features of these tumours have not been elucidated in detail. We carried out whole‐exome sequencing (WES), copy number, and transcriptome analysis of bladder SCC. Muscle‐invasive bladder cancer (MIBC) samples with no evidence of squamous differentiation (non‐SD) were used for comparison. To assess commonality of features with urothelial carcinoma with SD, we examined data from SD samples in The Cancer Genome Atlas (TCGA) study of MIBC. TP53 was the most commonly mutated gene in SCC (64%) followed by FAT1 (45%). Copy number analysis revealed complex changes in SCC, many differing from those in samples with SD. Gain of 5p and 7p was the most common feature, and focal regions on 5p included OSMR and RICTOR. In addition to 9p deletions, we found some samples with focal gain of 9p24 containing CD274 (PD‐L1). Loss of 4q35 containing FAT1 was found in many samples such that all but one sample analysed by WES had FAT1 mutation or deletion. Expression features included upregulation of oncostatin M receptor (OSMR), metalloproteinases, metallothioneins, keratinisation genes, extracellular matrix components, inflammatory response genes, stem cell markers, and immune response modulators. Exploration of differentially expressed transcription factors identified BNC1 and TFAP2A, a gene repressed by PPARG, as the most upregulated factors. Known urothelial differentiation factors were downregulated along with 72 Kruppel‐associated (KRAB) domain‐containing zinc finger family protein (KZFP) genes. Novel therapies are urgently needed for these tumours. In addition to upregulated expression of EGFR, which has been suggested as a therapeutic target in basal/squamous bladder cancer, we identified expression signatures that indicate upregulated OSMR and YAP/TAZ signalling. Preclinical evaluation of the effects of inhibition of these pathways alone or in combination is merited.
Scrutinizing high‐risk patients from ASC‐US cytology via a deep learning model
Authors: Tao Xiang , Chu Xiao , Guo Bingxue , Pan Qiuzhi , Ji Shuting , Lou Wenjie , Lv Chuanfeng , Xie Guotong , Hua Keqin 
Published: March 2022

BACKGROUNDAtypical squamous cells of undetermined significance (ASC‐US) is the most frequent but ambiguous abnormal Papanicolaou (Pap) interpretation and is generally triaged by high‐risk human papillomavirus (hrHPV) testing before colposcopy. This study aimed to evaluate the performance of an artificial intelligence (AI)‐based triage system to predict ASC‐US cytology for cervical intraepithelial neoplasia 2+ lesions (CIN2+).METHODSMore than 60,000 images were used to train this proposed deep learning‐based ASC‐US triage system, where both cell‐level and slide‐level information were extracted. In total, 1967 consecutive ASC‐US Paps from 2017 to 2019 were included in this study. Histological follow‐ups were retrieved to compare the triage performance between the AI system and hrHPV in 622 patients with simultaneous hrHPV testing.RESULTSIn the triage of women with ASC‐US cytology for CIN2+, our system attained equivalent sensitivity (92.9%; 95% confidence interval [CI], 75.0%‐98.8%) and higher specificity (49.7%; 95% CI, 45.6%‐53.8%) than hrHPV testing (sensitivity: 89.3%; 95% CI, 70.6%‐97.2%; specificity: 34.3%; 95% CI, 30.6%‐38.3%) without requiring additional patient examination or testing. Additionally, the independence of this system from hrHPV testing (κ = 0.138) indicated that these 2 different methods could be used to triage ASC‐US as an alternative way.CONCLUSIONThis de novo deep learning‐based system can triage ASC‐US cytology for CIN2+ with a performance superior to hrHPV testing and without incurring additional expenses.;