bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pan-kidney cancer study identifies subtype specific perturbations on pathways with potential drivers in renal cell carcinoma
Authors: Zhan Xiaohui , Liu Yusong , Yu Christina Y. , Wang Tian-Fu , Zhang Jie , Ni Dong , Huang Kun 
Published: December 2020

Abstract
Background
Renal cell carcinoma (RCC) is a complex disease and is comprised of several histological subtypes, the most frequent of which are clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (PRCC) and chromophobe renal cell carcinoma (ChRCC). While lots of studies have been performed to investigate the molecular characterizations of different subtypes of RCC, our knowledge regarding the underlying mechanisms are still incomplete. As molecular alterations are eventually reflected on the pathway level to execute certain biological functions, characterizing the pathway perturbations is crucial for understanding tumorigenesis and development of RCC.

Methods
In this study, we investigated the pathway perturbations of various RCC subtype against normal tissue based on differential expressed genes within a certain pathway. We explored the potential upstream regulators of subtype-specific pathways with Ingenuity Pathway Analysis (IPA). We also evaluated the relationships between subtype-specific pathways and clinical outcome with survival analysis.

Results
In this study, we carried out a pathway-based analysis to explore the mechanisms of various RCC subtypes with TCGA RNA-seq data. Both commonly altered pathways and subtype-specific pathways were detected. To identify the distinctive characteristics of each subtype, we focused on subtype-specific perturbed pathways. Specifically, we observed that some of the altered pathways were regulated by several recurrent upstream regulators which presenting different expression patterns among distinct RCC subtypes. We also noticed that a large number of perturbed pathways were controlled by the subtype-specific upstream regulators. Moreover, we also evaluated the relationships between perturbed pathways and clinical outcome. Prognostic pathways were identified and their roles in tumor development and progression were inferred.

Conclusions
In summary, we evaluated the relationships among pathway perturbations, upstream regulators and clinical outcome for differential subtypes in RCC. We hypothesized that the alterations of common upstream regulators as well as subtype-specific upstream regulators work together to affect the downstream pathway perturbations and drive cancer initialization and prognosis. Our findings not only increase our understanding of the mechanisms of various RCC subtypes, but also provide targets for personalized therapeutic intervention.
Differential alternative splicing between hepatocellular carcinoma with normal and elevated serum alpha-fetoprotein
Authors: Jin Young-Joo , Aycheh Habtamu Minassie , Han Seonggyun , Chamberlin John , Shin Jaehang , Byun Seyoun , Lee Younghee 
Published: December 2020

AbstractBackgroundSerum alpha-fetoprotein (AFP) is the approved serum marker for hepatocellular carcinoma (HCC) screening. However, not all HCC patients show high (≥ 20 ng/mL) serum AFP, and the molecular mechanisms of HCCs with normal (< 20 ng/mL) serum AFP remain to be elucidated. Therefore, we aimed to identify biological features of HCCs with normal serum AFP by investigating differential alternative splicing (AS) between HCCs with normal and high serum AFP.MethodsWe performed a genome-wide survey of AS events in 249 HCCs with normal (n = 131) and high (n = 118) serum AFP levels using RNA-sequencing data obtained from The Cancer Genome Atlas.ResultsIn group comparisons of RNA-seq profiles from HCCs with normal and high serum AFP levels, 161 differential AS events (125 genes; ΔPSI > 0.05, FDR < 0.05) were identified to be alternatively spliced between the two groups. Those genes were enriched in cell migration or proliferation terms such as “the cell migration and growth-cone collapse” and “regulation of insulin-like growth factor (IGF) transport and uptake by IGF binding proteins”. Most of all, two AS genes (FN1andFAM20A) directly interact with AFP; these relate to the regulation of IGF transport and post-translational protein phosphorylation. Interestingly, 42 genes and 27 genes were associated with gender and vascular invasion (VI), respectively, but only eighteen genes were significant in survival analysis. We especially highlight thatFN1exhibited increased differential expression of AS events (ΔPSI > 0.05), in which exons 25 and 33 were more frequently skipped in HCCs with normal (low) serum AFP compared to those with high serum AFP. Moreover, these events were gender and VI dependent.ConclusionWe found that AS may influence the regulation of transcriptional differences inherent in the occurrence of HCC maintaining normal rather than elevated serum AFP levels.
Outdoor air pollution from industrial chemicals causing new onset of asthma or COPD: a systematic review protocol
Authors: Lux Harald , Baur Xaver , Budnik Lygia Therese , Heutelbeck Astrid , Teixeira João Paulo , Neumann Emeri , Adliene Diana , Puišo Judita , Lucas David , Löndahl Jakob , Damialis Athanasios , Goksel Ozlem , Orru Hans 
Published: December 2020

AbstractBackgroundUntil today, industrial sources contribute to the multifaceted contamination of environmental air. Exposure to air pollutants has the potential to initiate and promote asthma and chronic obstructive pulmonary disease (COPD). At global scale, both entities cause the majority of about 4 million annual deaths by respiratory disease. However, we identified industrial contamination as a subgroup of air pollution that may be associated with this burden and is underinvestigated in research. Therefore, the aim of this study is to investigate associations between substances industrially released into environmental air and the occurrence of asthma and COPD in the human population. Here we present the protocol for our systematic review of the current evidence.MethodsThe following determinations will be applied during the systematic review process and are specified in the protocol that complies with the PRISMA-P statement. Populations of children and adults, as well as outdoor workers, exposed to industrially released air pollutants are of interest. Eligible studies may include subjects as controls who are non- or less exposed to the investigated air pollutants. The outcomes new-onset asthma and/or COPD investigated with risk ratio, odds ratio, hazard ratio, incidence rate ratio, cumulative incidence, and incidence rate are eligible. We will search the electronic literature databases EMBASE, MEDLINE, and Web of Science for peer-reviewed reports of incidence studies and incidence case-control studies. After systematic sorting of initial records, included studies will be subjected to quality assessment. Data will be synthesized qualitatively and, if appropriate, quantitatively for risk ratio and odds ratio. We will maintain and provide a PRISMA report.DiscussionResults of this systematic review may indicate alterations of incidence and risk of asthma and/or COPD in populations within industrial exposure radiuses including outdoor workplaces. Specific causal substances and compositions will be identified, but results will depend on the exposure assessment of the eligible studies. Our approach covers effects of industrial contributions to overall air pollution if studies reportedly attribute investigated emissions to industry. Results of this study may raise the question wether the available higher-level evidence sufficiently covers the current scale of industrial exposure scenarios and their potential harm to respiratory health.Trial registrationThis protocol was registered in PROSPERO, registration numberCRD42020151573.
Accuracy and precision of zero-echo-time, single- and multi-atlas attenuation correction for dynamic [11C]PE2I PET-MR brain imaging
Authors: Sousa João M. , Appel Lieuwe , Merida Inés , Heckemann Rolf A. , Costes Nicolas , Engström Mathias , Papadimitriou Stergios , Nyholm Dag , Ahlström Håkan , Hammers Alexander , Lubberink Mark 
Published: December 2020

Abstract
Background
A valid photon attenuation correction (AC) method is instrumental for obtaining quantitatively correct PET images. Integrated PET/MR systems provide no direct information on attenuation, and novel methods for MR-based AC (MRAC) are still under investigation. Evaluations of various AC methods have mainly focused on static brain PET acquisitions. In this study, we determined the validity of three MRAC methods in a dynamic PET/MR study of the brain.

Methods
Nine participants underwent dynamic brain PET/MR scanning using the dopamine transporter radioligand [11C]PE2I. Three MRAC methods were evaluated: single-atlas (Atlas), multi-atlas (MaxProb) and zero-echo-time (ZTE). The 68Ge-transmission data from a previous stand-alone PET scan was used as reference method. Parametric relative delivery (R1) images and binding potential (BPND) maps were generated using cerebellar grey matter as reference region. Evaluation was based on bias in MRAC maps, accuracy and precision of [11C]PE2I BPND and R1 estimates, and [11C]PE2I time-activity curves. BPND was examined for striatal regions and R1 in clusters of regions across the brain.

Results
For BPND, ZTE-MRAC showed the highest accuracy (bias < 2%) in striatal regions. Atlas-MRAC exhibited a significant bias in caudate nucleus (− 12%) while MaxProb-MRAC revealed a substantial, non-significant bias in the putamen (9%). R1 estimates had a marginal bias for all MRAC methods (− 1.0–3.2%). MaxProb-MRAC showed the largest intersubject variability for both R1 and BPND. Standardized uptake values (SUV) of striatal regions displayed the strongest average bias for ZTE-MRAC (~ 10%), although constant over time and with the smallest intersubject variability. Atlas-MRAC had highest variation in bias over time (+10 to − 10%), followed by MaxProb-MRAC (+5 to − 5%), but MaxProb showed the lowest mean bias. For the cerebellum, MaxProb-MRAC showed the highest variability while bias was constant over time for Atlas- and ZTE-MRAC.

Conclusions
Both Maxprob- and ZTE-MRAC performed better than Atlas-MRAC when using a 68Ge transmission scan as reference method. Overall, ZTE-MRAC showed the highest precision and accuracy in outcome parameters of dynamic [11C]PE2I PET analysis with use of kinetic modelling.
Sentience and transcendence: personal reflections on physical and mental adaptation from a near-death event and life-limiting surgery
Authors: Ramsay James 
Published: December 2020

SummaryIn this article I reflect on my experience of adapting physically, mentally and spiritually to a medical trauma that had life-changing consequences. I consider how, over 7 years to the time of writing, mental difficulties were inseparable from the physical; and how, for me, both are aspects of a form of understanding knowable only as mystery. Writing from a position of religious faith, I try to convey my experiences in a way that will be of interest to others regardless of their views. At the end, I reflect on aspects of my care that might be particularly relevant for a holistic, person-centred therapeutic approach.
Psychiatry and neurodevelopmental disorders: experts by experience, clinical care and research
Authors: Alexander Regi T. , Langdon Peter E. , O'Hara Jean , Howell Andreana , Lane Tadhgh , Tharian Reena , Shankar Rohit 
Published: December 2020

SummaryPeople with neurodevelopmental disorders often present with challenging behaviours and psychiatric illnesses. Diagnosis and treatment require patients, families and healthcare professionals to work closely together in partnership, acknowledging their respective areas of expertise. Good treatment outcomes should also be underpinned by robust research evidence. Key research priorities are highlighted.
Spinach and Chive for Kidney Tubule Engineering: the Limitations of Decellularized Plant Scaffolds and Vasculature
Authors: Jansen Katja , Evangelopoulou Marianna , Pou Casellas Carla , Abrishamcar Sarina , Jansen Jitske , Vermonden Tina , Masereeuw Rosalinde 
Published: December 2020

AbstractTissue decellularization yields complex scaffolds with retained composition and structure, and plants offer an inexhaustible natural source of numerous shapes. Plant tissue could be a solution for regenerative organ replacement strategies and advanced in vitro modeling, as biofunctionalization of decellularized tissue allows adhesion of various kinds of human cells that can grow into functional tissue. Here, we investigated the potential of spinach leaf vasculature and chive stems for kidney tubule engineering to apply in tubular transport studies. We successfully decellularized both plant tissues and confirmed general scaffold suitability for topical recellularization with renal cells. However, due to anatomical restrictions, we believe that spinach and chive vasculature themselves cannot be recellularized by current methods. Moreover, gradual tissue disintegration and deficient diffusion capacity make decellularized plant scaffolds unsuitable for kidney tubule engineering, which relies on transepithelial solute exchange between two compartments. We conclude that plant-derived structures and biomaterials need to be carefully considered and possibly integrated with other tissue engineering technologies for enhanced capabilities.
Chimalpahin’s Nahua Authority: Modifying a Spanish Account of the Conquest of Mexico
Authors: Rodriguez Veronica 
Published: December 2020

AbstractThis article provides an analysis of Chimalpahin’s additions to Francisco López de Gómara’s Historia de la conquista de México. In his account, Chimalpahin draws attention to the plurality of ethnic states, their cultural practices, and political conflicts. In this article, the author argues that Chimalpahin’s modifications depict a Nahua version of the conquest in which the emphasis on the native’s active participation reflects its effect in the outcome of the war even though such contributions are often unseen in the most representative narratives of the event. It shows that Chimalpahin participates in the production of an indigenous collective memory and that he had the agency to create an account that clarifies, and even challenges, Spanish-centered narratives such as López de Gómara’s work.
Fitness Trends From Around the Globe
Authors: Kercher Vanessa Marie , Kercher Kyle , Bennion Trevor , Yates Brandon A. , Feito Yuri , Alexander Chris , Amaral Paulo Costa , Soares Waldyr , Li Yong-Ming , Han Jia , Liu Yang , Wang Ran , Huang Hai-Yan , Gao Bing-Hong , Batrakoulis Alexios , Chávez Francisco Gómez , Haro Jorge López , Zavalza Adrián Ricardo Pelayo , Rodríguez Luis Eduardo Aguirre , Veiga Oscar L. , Valcarce-Torrente Manel , De la Cámara Miguel Á. 
Published: December 2020

Apply It!
From this article, the reader should be able to do the following:
• Identify top 20 fitness trends for Australia, Brazil, China, Europe, Mexico, Spain, and the United States
• Recognize individual and unique fitness trends represented within Australia, Brazil, China, Europe, Mexico, Spain, and the United States
Estimating the Critical Parameter in Almost Stochastic Dominance from Insurance Deductibles
Authors: Huang Yi-Chieh , Kan Kamhon , Tzeng Larry Y. , Wang Kili C. 
Published: December 2020

Knowing how small a violation of stochastic dominance rules would be accepted by most individuals is a prerequisite to applying almost stochastic dominance criteria. Unlike previous laboratory-experimental studies, this paper estimates an acceptable violation of stochastic dominance rules with 939,690 real world data observations on a choice of deductibles in automobile theft insurance. We find that, for all policyholders in the sample who optimally chose a low deductible, the upper bound estimate of the acceptable violation ratio is 0.0014, which is close to zero. On the other hand, considering that most decision makers, such as 99% (95%) of the policyholders in the sample, optimally chose the low deductible, the upper bound estimate of the acceptable violation ratio is 0.0405 (0.0732). Our results provide reference values for the acceptable violation ratio for applying almost stochastic dominance rules. This paper was accepted by Manel Baucells, decision analysis.
Symptoms of Autism Spectrum Disorder in Children With Down Syndrome and Williams Syndrome
Authors: Kirchner Rebecca M. , Walton Katherine M. 
Published: December 2020

Abstract
Research suggests that people with a Williams syndrome (WS) or Down syndrome (DS) diagnosis display an increased prevalence of autism spectrum disorder (ASD) when compared to the general population. This study aimed to examine characteristics of ASD in a group of children with DS or WS. Results suggest that children with DS and WS exhibit higher levels of autism symptoms than the general population, particularly in the area of unusual behaviors, and that these elevations are not solely due to deficits in adaptive behavior. There are many possible explanations for these elevations, such as issues with measurement, etiological overlap, or similar behavioral phenotypes. More research is needed to further our understanding of the overlap of ASD symptoms in these populations.
Blood test dynamics in hospitalized COVID-19 patients: Potential utility of D-dimer for pulmonary embolism diagnosis
Authors: Cerdà Pau , Ribas Jesus , Iriarte Adriana , Mora-Luján José María , Torres Raquel , del Río Belén , Jofre Héctor Ignacio , Ruiz Yolanda , Huguet Marta , Fuset Mari Paz , Martínez-Yélamos Sergio , Santos Salud , Llecha Núria , Corbella Xavier , Riera-Mestre Antoni 
Published: December 2020

Background
A higher incidence of thrombotic events, mainly pulmonary embolism (PE), has been reported in hospitalized patients with COVID-19. The main objective was to assess clinical and laboratory differences in hospitalized COVID-19 patients according to occurrence of PE.

Methods
This retrospective study included all consecutive patients hospitalized with COVID-19 who underwent a computed tomography (CT) angiography for PE clinical suspicion. Clinical data and median blood test results distributed into weekly periods from COVID-19 symptoms onset, were compared between PE and non-PE patients.

Results
Ninety-two patients were included, 29 (32%) had PE. PE patients were younger (63.9 (SD 13.7) vs 69.9 (SD 12.5) years). Clinical symptoms and COVID-19 CT features were similar in both groups. PE was diagnosed after a mean of 20.0 (SD 8.6) days from the onset of COVID-19 symptoms. Corticosteroid boluses were more frequently used in PE patients (62% vs. 43%). No patients met ISTH DIC criteria. Any parameter was statistically significant or clinically relevant except for D-Dimer when comparing both groups. Median values [IQR] of D-dimer in PE vs non-PE patients were: week 2 (2010.7 [770.1–11208.9] vs 626.0 [374.0–2382.2]; p = 0.004); week 3 (3893.1 [1388.2–6694.0] vs 1184.4 [461.8–2447.8]; p = 0.003); and week 4 (2736.3 [1202.1–8514.1] vs 1129.1 [542.5–2834.6]; p = 0.01). Median fold-increase of D-dimer between week 1 and 2 differed between groups (6.64 [3.02–23.05] vs 1.57 [0.64–2.71], p = 0.003); ROC curve AUC was 0.879 (p = 0.003) with a sensitivity and specificity for PE of 86% and 80%, respectively.

Conclusions
Among hospitalized COVID-19 patients, D-dimer levels are higher at weeks 2, 3 and 4 after COVID-19 symptom onset in patients who develop PE. This difference is more pronounced when the fold increase between weeks 1 and 2 is compared.
Occupational exposures and exacerbations of asthma and COPD—A general population study
Authors: Skaaby Stinna , Flachs Esben Meulengracht , Lange Peter , Schlünssen Vivi , Marott Jacob Louis , Brauer Charlotte , Nordestgaard Børge G. , Sadhra Steven , Kurmi Om , Bonde Jens Peter Ellekilde 
Published: December 2020

Purpose
Recent studies suggest that occupational inhalant exposures trigger exacerbations of asthma and chronic obstructive pulmonary disease, but findings are conflicting.

Methods
We included 7,768 individuals with self-reported asthma (n = 3,215) and/or spirometric airflow limitation (forced expiratory volume in 1 second (FEV1)/ forced expiratory volume (FVC) <0.70) (n = 5,275) who participated in The Copenhagen City Heart Study or The Copenhagen General Population Study from 2001–2016. Occupational exposure was assigned by linking job codes with job exposure matrices, and exacerbations were defined by register data on oral corticosteroid treatment, emergency care unit assessment or hospital admission. Associations between occupational inhalant exposure each year of follow-up and exacerbation were assessed by Cox regression with time varying exposure and age as the underlying time scale.

Results
Participants were followed for a median of 4.6 years (interquartile range, IQR 5.4), during which 870 exacerbations occurred. Exacerbations were not associated with any of the selected exposures (high molecular weight sensitizers, low molecular weight sensitizers, irritants or low and high levels of mineral dust, biological dust, gases & fumes or the composite variable vapours, gases, dusts or fumes). Hazards ratios ranged from 0.8 (95% confidence interval: 0.7;1.0) to 1.2 (95% confidence interval: 0.9;1.7).

Conclusion
Exacerbations of obstructive airway disease were not associated with occupational inhalant exposures assigned by a job exposure matrix. Further studies with alternative exposure assessment are warranted.
Ethnic variation and the relevance of homozygous RNF 213 p.R4810.K variant in the phenotype of Indian Moya moya disease
Authors: K. Arun , Shafeeque C. M. , Sudhir Jayanand B. , Banerjee Moinak , P. N. Sylaja 
Published: December 2020

Background and purpose
Polymorphisms in Ring Finger Protein 213 (RNF 213) gene have been detected to confer genetic susceptibility to Moya moya disease (MMD) in the East Asian population. We investigated the frequency of RNF 213 gene polymorphism and its association with MMD phenotypes in the Indian population.

Materials and methods
A case-control study for RNF 213 polymorphism involving 65 MMD patients, 75 parents, and 120 controls were performed. A total of 21 SNPs were screened, of which 17 SNPs were monomorphic. Allelic and genotypic frequency of all polymorphic SNPs were assessed and its association with MMD phenotypes was evaluated.

Results
The median age of symptom onset was 9 (range 2–17) and 37 years (range 20–58) in paediatric and adult patients respectively. A strong association was observed with RNF 213 rs112735431(p.R4810K) and MMD. Out of 65 patients with MMD, five patients carried the homozygous risk AA genotype. None of the healthy controls carried this homozygous mutation. The mutant allele was detected in MMD patients from Tamil Nadu and North eastern states of India (p = <0.0001). All the patients carrying the mutant allele had an early age of onset (p = <0.0001), higher incidence of bilateral disease (p = <0.002), positive family history (p = 0.03), higher Suzuki angiographic stage (≥3) (p<0.0006) and recurrent neurological events (ischemic strokes and TIAs) (p = <0.009).

Conclusion
The homozygous rs112735431(p.R4810K) variant in RNF 213 variant not only predicts the risk for MMD but can also predict the phenotypic variants.