bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disagreement between patient‐ and physician‐reported outcomes on symptomatic adverse events as poor prognosis in patients treated with first‐line cetuximab plus chemotherapy for unresectable metastatic colorectal cancer: Results of Phase II QUACK trial
Authors: Ooki Akira , Morita Satoshi , Tsuji Akihito , Iwamoto Shigeyoshi , Hara Hiroki , Tanioka Hiroaki , Satake Hironaga , Kataoka Masato , Kotaka Masahito , Kagawa Yoshinori , Nakamura Masato , Shingai Tatsushi , Ishikawa Masashi , Miyake Yasuhiro , Suto Takeshi , Hashiguchi Yojiro , Yabuno Taichi , Ando Masahiko , Sakamoto Junichi , Yamaguchi Kensei 
Published: November 2020

AbstractThe status and prognostic value of the disagreement between physician and patient assessments of symptomatic adverse events (AEs) remain unclear for patients with metastatic colorectal cancer treated with first‐line cetuximab plus chemotherapy. Paired data on patient‐reported outcomes using the EORTC QLQ‐C30 and physician‐reported outcomes using the NCI‐CTCAE for eight symptomatic AEs (fatigue, pain, insomnia, dyspnea, constipation, appetite loss, nausea/vomiting, and diarrhea) were collected from a prospective trial assessing the relationships between treatment efficacy, AEs, and quality of life. The overall agreement rates between patient and physician reporting at 4 weeks ranged from 40.2% to 76.5% for 129 patients. The level of agreement based on Cohen's κ statistics was slight to poor for dyspnea, pain, fatigue, and insomnia, while it was moderate to fair for the remaining AEs. No clinicopathological characteristics of disagreement were found. The underreporting by physicians ranged from 12.5% (nausea/vomiting) to 56.7% (fatigue). The 2‐year overall survival (OS) rate was more favorable for patients with high agreement than for those with low agreement (71.2% vs. 46.5%, p = .016), and the agreement status was an independent factor of OS (HR, 2.31; 95% CI, 1.13–4.71; p = .022). For patients who were reported as asymptomatic by the physician, the presence of patient‐reported symptoms resulted in a trend toward poor prognostic outcomes for appetite loss, dyspnea, diarrhea, and constipation. These findings provide the clinical importance of the monitoring of patient‐reported symptoms that can be complementary to physician‐reported data to ensure more accurate clinical outcomes.
Endovascular removal of a misplaced ureteral stent in the vena cava: a complication of ultrasound‐guided percutaneous nephrolithotomy
Authors: Hu Chao , Zhu Anyi , Zhu Xianhua , Liang Ting , Lu Xiongbing 
Published: November 2020

AbstractIntravascular migration of a double J stent into the inferior vena cava is an uncommon complication. Active prevention, timely diagnosis, and early intervention are crucial for this complication. Intravascular interventional therapy is relatively easy, less traumatic, and has a high success rate. It can be used to select patients for intravascular ectopic DJS treatment.
Spontaneous rupture of a degenerated leiomyoma causing peritonitis and ileus during pregnancy: A case report
Authors: Odagami Mizuha , Makino Mutsuko , Miyagi Etsuko , Aoki Shigeru 
Published: November 2020

AbstractDegenerated leiomyomas can rupture during pregnancy, and leakage of the fluid causes peritonitis in rare cases. If peritonitis associated with a degenerated leiomyoma is observed, the occurrence of rupture of the leiomyoma should be considered.
Surface Modified Persistent Luminescence Probes for Biosensing and Bioimaging: A Review
Authors: Luo Qiang , Wang Wenjie , Tan Jie , Yuan Quan 
Published: November 2020

AbstractPersistent luminescence materials (PLMs) are a class of unique luminescent materials that can remain luminescent for a few milliseconds to days without constant excitation. By virtue of the super long decay time, PLMs have been extensively explored in biosensing and bioimaging applications to elimin ate autofluorescence interference and improve signal‐to‐noise ratio in complex samples and tissues. However, nude PLMs often suffer from the poor stability, selectivity, and biocompatibility in biological system and in vivo, which greatly impedes their applications in biomedicine and bioanalysis. Remarkably, surface modification is a viable solution that endows PLMs with span‐new features and can make PLMs suitable for organisms by altering PLMs’ interaction with biological system. In this review, commonly used strategies for surface modification of PLMs are briefly introduced, and the applications of surface modified PLMs in biosensing and bioimaging as well as their challenges are summarized.image
Extended cubic B‐spline collocation method for singularly perturbed parabolic differential‐difference equation arising in computational neuroscience
Authors: Daba Imiru Takele , Duressa Gemechis File 
Published: November 2020

AbstractA parameter uniform numerical method is presented for solving singularly perturbed parabolic differential‐difference equations with small shift arguments in the reaction terms arising in computational neuroscience. To approximate the terms with the shift arguments, Taylor's series expansion is used. The resulting singularly perturbed parabolic differential equation is solved by applying the implicit Euler method in temporal direction and extended cubic B‐spline basis functions consisting of a free parameter λ for the resulting system of ordinary differential equations in the spatial direction. The proposed method is shown to be accurate of order by preserving an ε− uniform convergence. To demonstrate the applicability of the proposed method, two test examples are solved by the method and the numerical results are compared with some existing results. The obtained numerical results agreed with the theoretical results.
3D Oral and Cervical Tissue Models for Studying Papillomavirus Host‐Pathogen Interactions
Authors: Jackson Robert , Maarsingh Jason D. , Herbst‐Kralovetz Melissa M. , Van Doorslaer Koenraad 
Published: November 2020

AbstractHuman papillomavirus (HPV) infection occurs in differentiating epithelial tissues. Cancers caused by high‐risk types (e.g., HPV16 and HPV18) typically occur at oropharyngeal and anogenital anatomical sites. The HPV life cycle is differentiation‐dependent, requiring tissue culture methodology that is able to recapitulate the three‐dimensional (3D) stratified epithelium. Here we report two distinct and complementary methods for growing differentiating epithelial tissues that mimic many critical morphological and biochemical aspects of in vivo tissue. The first approach involves growing primary human epithelial cells on top of a dermal equivalent consisting of collagen fibers and living fibroblast cells. When these cells are grown at the liquid‐air interface, differentiation occurs and allows for epithelial stratification. The second approach uses a rotating wall vessel bioreactor. The low‐fluid‐shear microgravity environment inside the bioreactor allows the cells to use collagen‐coated microbeads as a growth scaffold and self‐assemble into 3D cellular aggregates. These approaches are applied to epithelial cells derived from HPV‐positive and HPV‐negative oral and cervical tissues. The second part of the article introduces potential downstream applications for these 3D tissue models. We describe methods that will allow readers to start successfully culturing 3D tissues from oral and cervical cells. These tissues have been used for microscopic visualization, scanning electron microscopy, and large omics‐based studies to gain insights into epithelial biology, the HPV life cycle, and host‐pathogen interactions. © 2020 Wiley Periodicals LLC.Basic Protocol 1: Establishing human primary cell–derived 3D organotypic raft culturesSupport Protocol 1: Isolation of epithelial cells from patient‐derived tissuesSupport Protocol 2: Growth and maintenance of primary human epithelial cells in monolayer cultureSupport Protocol 3: PCR‐based HPV screening of primary cell culturesBasic Protocol 2: Establishing human 3D cervical tissues using the rotating wall vessel bioreactorSupport Protocol 4: Growth and maintenance of human A2EN cells in monolayer cultureSupport Protocol 5: Preparation of the slow‐turning lateral vessel bioreactorSupport Protocol 6: Preparation of Cytodex‐3 microcarrier beadsBasic Protocol 3: Histological assessment of 3D organotypic raft tissuesBasic Protocol 4: Spatial analysis of protein expression in 3D organotypic raft culturesBasic Protocol 5: Immunofluorescence imaging of RWV‐derived 3D tissuesBasic Protocol 6: Ultrastructural visualization and imaging of RWV‐derived 3D tissuesBasic Protocol 7: Characterization of gene expression by RT‐qPCR
Involvement of activated cytotoxic T lymphocytes and natural killer cells in Henoch–Schönlein purpura nephritis
Authors: Imai Takashi , Nishiyama Kei , Ueki Kenji , Tanaka Tamami , Kaku Yoshitsugu , Hara Toshiro , Ohga Shouichi 
Published: November 2020

AbstractObjectivesImmunoglobulin A vasculitis/Henoch–Schönlein purpura (IgAV/HSP) is a major cause of vasculitis in children. It is often accompanied by nephritis (HSPN) and could progress to chronic kidney disease. Galactose‐deficient IgA1 was recently reported to be involved in the pathogenesis of HSPN, for which immunosuppressive drugs are considered key treatment. However, the involvement of immune cells in the development of HSPN remains unclear.MethodsWe compared gene expressions of peripheral blood mononuclear cells (PBMCs) among healthy controls (n = 10), IgAV/HSP patients (n = 21) and HSPN patients (n = 8), which required nephritis development within 3 months of IgAV/HSP onset. Immunohistochemistry analysis and flow cytometry were performed to assess renal biopsy specimens and PBMCs, respectively. Serum CX3CL1 levels were measured by ELISA.ResultsGNLY and GZMB expressions increased in HSPN patients, consistent with increased number of glomerular granulysin‐ and/or granzyme B‐positive cells demonstrated by immunohistochemistry analysis. Additionally, circulating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells were activated with the up‐regulated surface expressions of human leucocyte antigen DR (HLA‐DR) and CX3CR1 in HSPN patients with severe proteinuria. Renal biopsies demonstrated increased number of CD8+ cells and/or CD56+ cells and up‐regulated expression of glomerular CX3CL1, a specific ligand for CX3CR1, along with increased serum CX3CL1 level.ConclusionActivated CTLs and NK cells play roles in the development of nephritis in IgAV/HSP patients and can be used as novel biomarkers for HSPN.
The application of community ecology theory to co‐infections in wildlife hosts
Authors: Ramsay Chloe , Rohr Jason R. 
Published: November 2020

AbstractPriority effect theory, a foundational concept from community ecology, states that the order and timing of species arrival during species assembly can affect species composition. Although this theory has been applied to co‐infecting parasite species, it has almost always been with a single time lag between co‐infecting parasites. Thus, how the timing of parasite species arrival affects co‐infections and disease remains poorly understood. To address this gap in the literature, we exposed postmetamorphic Cuban tree frogs (Osteopilus septentrionalis) to Ranavirus, the fungus Batrachochytrium dendrobatidis (Bd), a nematode Aplectana hamatospicula, or pairs of these parasites either simultaneously or sequentially at a range of time lags and quantified load of the secondary parasite and host growth, survival, and parasite tolerance. Prior exposure to Bd or A. hamatospicula significantly increased viral loads relative to hosts singly infected with Ranavirus, whereas A. hamatospicula loads in hosts were higher when coexposed to Bd than when coexposed to Ranavirus. There was a significant positive relationship between time since Ranavirus infection and Bd load, and prior exposure to A. hamatospicula decreased Bd loads compared to simultaneous co‐infection with these parasites. Infections with Bd and Ranavirus either singly or in co‐infections decreased host growth and survival. This research reveals that time lags between co‐infections can affect parasite loads, in line with priority effects theory. As co‐infections in the field are unlikely to be simultaneous, an understanding of when co‐infections are impacted by time lags between parasite exposures may play a major role in controlling problematic co‐infections.
Ventricular tachycardia, premature ventricular contractions, and mortality in unselected patients with lung, colon, or pancreatic cancer: a prospective study
Authors: Anker Markus S. , von Haehling Stephan , Coats Andrew J.S. , Riess Hanno , Eucker Jan , Porthun Jan , Butler Javed , Karakas Mahir , Haverkamp Wilhelm , Landmesser Ulf , Anker Stefan D. 
Published: November 2020

AbstractAimsMany cancer patients die due to cardiovascular disease and sudden death, but data on ventricular arrhythmia prevalence and prognostic importance are not known.Methods and resultsBetween 2005 and 2010, we prospectively enrolled 120 unselected patients with lung, colon, or pancreatic cancer due to one of three diagnoses: colorectal (n = 33), pancreatic (n = 54), or non‐small cell lung cancer (n = 33). All were free of manifest cardiovascular disease. They were compared to 43 healthy controls similar in age and sex distribution. Each participant underwent 24 h electrocardiogram recording and cancer patients were followed for up to 12.5 years for survival (median 21 months). Ninety‐six cancer patients (80%) died during follow‐up [5‐year survival: 27% (95% confidence interval 19–35%)]. Non‐sustained ventricular tachycardia (NSVT) was more frequent in cancer patients vs. controls (8% vs. 0%, P = 0.021). The number of premature ventricular contractions (PVCs) over 24 h was not increased in cancer patients vs. controls (median 4 vs. 9, P = 0.2). In multivariable analysis, NSVT [hazard ratio (HR) 2.44, P = 0.047] and PVCs (per 100, HR 1.021, P = 0.047) were both significant predictors of mortality, independent of other univariable mortality predictors including tumour stage, cancer type, potassium concentration, prior surgery, prior cardiotoxic chemotherapy, and haemoglobin. In patients with colorectal and pancreatic cancer, ≥50 PVCs/24 h predicted mortality (HR 2.30, P = 0.0024), and was identified in 18% and 26% of patients, respectively.ConclusionsNon‐sustained ventricular tachycardia is more frequent in unselected patients with colorectal, pancreatic, and non‐small cell lung cancer and together with PVCs predict long‐term mortality. This raises the prospect of cardiovascular mortality being a target for future treatment interventions in selected cancers.
Association between renin–angiotensin–aldosterone system inhibitor use and COVID‐19 hospitalization and death: a 1.4 million patient nationwide registry analysis
Authors: Savarese Gianluigi , Benson Lina , Sundström Johan , Lund Lars H. 
Published: November 2020

AbstractAimsRenin–angiotensin–aldosterone system inhibitors (RAASi) improve outcomes in cardiorenal disease but concerns have been raised over increased risk of incident hospitalization and death from coronavirus disease 2019 (COVID‐19). We investigated the association between use of angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs) and COVID‐19 hospitalization/death in a large nationwide population.Methods and resultsPatients with hypertension, heart failure, diabetes, kidney disease, or ischaemic heart disease registered in the Swedish National Patient Registry until 1 February 2020 were included and followed until 31 May 2020. COVID‐19 cases were defined based on hospitalization/death for COVID‐19. Multivariable logistic and Cox regressions were fitted to investigate the association between ACEi/ARB and MRA and risk of hospitalization/death for COVID‐19 in the overall population, and of all‐cause mortality in COVID‐19 cases. We performed consistency analysis to quantify the impact of potential unmeasured confounding. Of 1 387 746 patients (60% receiving ACEi/ARB and 5.8% MRA), 7146 (0.51%) had incident hospitalization/death from COVID‐19. After adjustment for 45 variables, ACEi/ARB use was associated with a reduced risk of hospitalization/death for COVID‐19 (odds ratio 0.86, 95% confidence interval 0.81–0.91) in the overall population, and with reduced mortality in COVID‐19 cases (hazard ratio 0.89, 95% confidence interval 0.82–0.96). MRA use was not associated with risk of any outcome. Consistency analysis showed that unmeasured confounding would need to be large for there to be harmful signals associated with RAASi use.ConclusionsIn a 1.4 million nationwide cohort, use of RAASi was not associated with increased risk of hospitalization for or death from COVID‐19.
Analysis of mutational signatures with yet another package for signature analysis
Authors: Hübschmann Daniel , Jopp‐Saile Lea , Andresen Carolin , Krämer Stephen , Gu Zuguang , Heilig Christoph E. , Kreutzfeldt Simon , Teleanu Veronica , Fröhling Stefan , Eils Roland , Schlesner Matthias 
Published: November 2020

AbstractDifferent mutational processes leave characteristic patterns of somatic mutations in the genome that can be identified as mutational signatures. Determining the contributions of mutational signatures to cancer genomes allows not only to reconstruct the etiology of somatic mutations, but can also be used for improved tumor classification and support therapeutic decisions. We here present the R package yet another package for signature analysis (YAPSA) to deconvolute the contributions of mutational signatures to tumor genomes. YAPSA provides in‐built collections from the COSMIC and PCAWG SNV signature sets as well as the PCAWG Indel signatures and employs signature‐specific cutoffs to increase sensitivity and specificity. Furthermore, YAPSA allows to determine 95% confidence intervals for signature exposures, to perform constrained stratified signature analyses to obtain enrichment and depletion patterns of the identified signatures and, when applied to whole exome sequencing data, to correct for the triplet content of individual target capture kits. With this functionality, YAPSA has proved to be a valuable tool for analysis of mutational signatures in molecular tumor boards in a precision oncology context. YAPSA is available at R/Bioconductor (http://bioconductor.org/packages/3.12/bioc/html/YAPSA.html).
Tumor‐only sequencing for oncology management: Germline‐focused analysis and implications
Authors: George Angela , Turnbull Clare 
Published: November 2020

AbstractAs patients are now routinely having large somatic genomic testing panels undertaken as part of routine management, there is the rising likelihood of uncovering the presence of a germline pathogenic variant. This may be found on testing undertaken on plasma (ctDNA) or tissue. This has led to the need for clear guidelines for oncologists about how to manage such results, including which variants require validation, how this should be undertaken, and what potential problems may arise. This requires an understanding of the limits of testing, and the pitfalls that may be encountered. In this review, we assess the frequency of detecting germline variants through tumor‐only sequencing, the necessary considerations for such information to be analyzed and the role of the molecular tumor board in considering results. We assess the additional considerations for interpretation of the underlying tumor, use of ctDNA or tissue for testing, clonal hematopoiesis, and hypermutation.
Neurophysiological mechanisms underlying motor feature binding processes and representations
Authors: Takacs Adam , Bluschke Annet , Kleimaker Maximilian , Münchau Alexander , Beste Christian 
Published: November 2020

AbstractCoherent, voluntary action requires an integrated representation of these actions and their defining features. Although theories delineate how action integration requiring binding between different action features may be accomplished, the underlying neurophysiological mechanisms are largely elusive. The present study examined the neurophysiological mechanisms underlying binding processes in actions. To this end, we conducted EEG recordings and applied standard event‐related potential analyses, temporal EEG signal decomposition and multivariate pattern analyses (MVPA). According to the code occupation account, an overlap between a planned and a to‐be‐performed action impairs performance. The level, to which performance is attenuated depends on the strength of binding of action features. This binding process then determines the representation of them, the so‐called action files. We show that code occupation and bindings between action features specifically modulate processes preceding motor execution as showed by the stimulus‐locked lateralized readiness potential (LRP). Conversely, motor execution processes reflected by the response‐locked LRP were not modulated by action file binding. The temporal decomposition of the EEG signal, further distinguished between action file related processes: the planned response determining code occupation was reflected in general (voluntary) response selection but not in involuntary (response priming‐related) activation. Moreover, MVPA on temporally decomposed neural signals indicated that action files are represented as a continuous chain of activations. Within this chain, inhibitory and response re‐activation patterns can be distinguished. Taken together, the neurophysiological correlates of action file binding suggest that parallel, stimulus‐ and response‐related pre‐motor processes are responsible for the code occupation in the human motor system.
COVID‐19 is increasing Ghanaian pregnant women’s anxiety and reducing healthcare seeking
Authors: Moyer Cheryl A. , Sakyi Kwame S. , Sacks Emma , Compton Sarah D. , Lori Jody R. , Williams John E. O. 
Published: November 2020

SynopsisPregnant women in Ghana report skipping antenatal care and reconsidering facility delivery due to concerns about COVID‐19.
Changes of lipid profiles in human umbilical vein endothelial cells exposed to zirconia nanoparticles with or without the presence of free fatty acids
Authors: Cheng Xiangjun , Guo Hao , Xian Youqi , Xie Xiaowei 
Published: November 2020

AbstractZirconia nanoparticles (NPs) have been widely used in biomedicine, which will likely lead to their interactions with endothelial cells (ECs). However, the toxicity of zirconia NPs to ECs is less investigated and the toxicological data are not consistent. Furthermore, no previous study, to the best of our knowledge, investigated the influence of zirconia NPs on lipid metabolism. This study investigated lipid profiles in human umbilical vein ECs (HUVECs) exposed to zirconia NPs with or without the presence of free fatty acids (FFAs). Incubation with FFA changed the hydrodynamic size, zeta potential, and surface profiles of zirconia NPs, indicating the surface coating effects. Exposure of HUVECs to various concentrations of zirconia NPs with or without the presence of FFA did not significantly decrease cellular viability, but FFA decreased zirconium elemental levels in NP‐exposed cells. Oil Red O staining showed that FFA or zirconia NPs and FFA, but not zirconia NPs alone, significantly increased lipid accumulation in HUVECs. Consistently, lipidomic data suggested that exposure to FFA or zirconia NPs and FFA up‐regulated most lipid classes in HUVECs. As the mechanisms for increased lipid accumulation, exposure to FFA or zirconia NPs and FFA up‐regulated endoplasmic reticulum (ER) stress axis IRE1α–XBP‐1, leading to increased FASN and ACSL3, proteins involved in lipid metabolism. Combined, our results demonstrated that zirconia NPs were noncytotoxic and showed minimal impact on ER stress‐mediated lipid metabolism in HUVECs under both normal and FFA‐challenged conditions, which indicated the relatively high biocompatibility of zirconia NPs to ECs.