bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of major and minor chicken allergens in dogs
Authors: Olivry Thierry , Pucheu‐Haston Cherie M. , Mayer Ursula , Bergvall Kerstin , Bexley Jennifer 
Published: November 2021

BackgroundAllergens targeted by serum‐specific immunoglobulin E (sIgE) in dogs clinically allergic to chicken have not been reported.ObjectivesTo characterise the allergens targeted by sIgE in dogs sensitised and allergic to chicken.AnimalsSera from three dogs not sensitised to chicken, from 10 chicken sensitised dogs and from 12 chicken allergic dogs.Methods and materialsEnzyme‐linked immunosorbent assay (ELISA) and immunoblotting with a commercial chicken extract were utilized. The bands identified on immunoblotting were sequenced by mass spectrometry for allergen characterization.ResultsUsing ELISA, we detected chicken‐sIgE above the positive threshold in zero of three (0%) nonsensitised dogs, five of five (100%) chicken‐sensitised dogs (a selection criterion), and in seven of 12 (58%) chicken‐allergic dogs. Immunoblotting performed with the same extract revealed IgE‐bound protein bands in 100% of all chicken‐sensitised and ‐allergic dogs, respectively. To identify the allergens, we excised the corresponding bands on the electrophoretic gel, and submitted them for sequencing by mass spectrometry. We conclusively identified seven major allergens (serum albumin, pyruvate kinase M, enolase 3, creatine kinase M, lactate dehydrogenase A, glyceraldehyde‐3‐phosphate dehydrogenase and triose‐phosphate isomerase) and one minor allergen (troponin C), which are relevant to dogs.Conclusions and clinical relevanceWe identified herein seven major chicken allergens for dogs, several of which are known to be cross‐reactive allergens for humans. Based on their degree of sequence identity, these allergens exhibit the theoretical potential to be cross‐reactive between poultry and mammalian meats; six of these allergens already are known to be cross‐reactive between chicken and fish species. Future studies should address the clinical relevance and cross‐reactivity potential of these chicken allergens in dogs.
SAM-Competitive PRMT5 Inhibitor PF-06939999 Demonstrates Antitumor Activity in Splicing Dysregulated NSCLC with Decreased Liability of Drug Resistance
Authors: Jensen-Pergakes Kristen , Tatlock John , Maegley Karen A. , McAlpine Indrawan J. , McTigue Michele , Xie Tao , Dillon Christopher P. , Wang Yuli , Yamazaki Shinji , Spiegel Noah , Shi Manli , Nemeth Amy , Miller Natalie , Hendrickson Eleanore , Lam Hieu , Sherrill John , Chung Chi-Yeh , McMillan Elizabeth A. , Bryant Shannon Karlicek , Palde Prakash , Braganza John , Brooun Alexei , Deng Ya-Li , Goshtasbi Vesta , Kephart Susan E. , Kumpf Robert A. , Liu Wei , Patman Ryan L. , Rui Eugene , Scales Stephanie , Tran-Dube Michelle , Wang Fen , Wythes Martin , Paul Thomas A. 
Published: November 2021

Abstract
Protein arginine methyltransferase 5 (PRMT5) overexpression in hematologic and solid tumors methylates arginine residues on cellular proteins involved in important cancer functions including cell-cycle regulation, mRNA splicing, cell differentiation, cell signaling, and apoptosis. PRMT5 methyltransferase function has been linked with high rates of tumor cell proliferation and decreased overall survival, and PRMT5 inhibitors are currently being explored as an approach for targeting cancer-specific dependencies due to PRMT5 catalytic function. Here, we describe the discovery of potent and selective S-adenosylmethionine (SAM) competitive PRMT5 inhibitors, with in vitro and in vivo characterization of clinical candidate PF-06939999. Acquired resistance mechanisms were explored through the development of drug resistant cell lines. Our data highlight compound-specific resistance mutations in the PRMT5 enzyme that demonstrate structural constraints in the cofactor binding site that prevent emergence of complete resistance to SAM site inhibitors. PRMT5 inhibition by PF-06939999 treatment reduced proliferation of non–small cell lung cancer (NSCLC) cells, with dose-dependent decreases in symmetric dimethyl arginine (SDMA) levels and changes in alternative splicing of numerous pre-mRNAs. Drug sensitivity to PF-06939999 in NSCLC cells associates with cancer pathways including MYC, cell cycle and spliceosome, and with mutations in splicing factors such as RBM10. Translation of efficacy in mouse tumor xenograft models with splicing mutations provides rationale for therapeutic use of PF-06939999 in the treatment of splicing dysregulated NSCLC.
Nuclear Receptor 4A2 (NR4A2/NURR1) Regulates Autophagy and Chemoresistance in Pancreatic Ductal Adenocarcinoma
Authors: Zarei Mehrdad , Shrestha Rupesh , Johnson Sneha , Yu Zuhua , Karki Keshav , Vaziri-Gohar Ali , Epps Jessica , Du Heng , Suva Larry , Zarei Mahsa , Safe Stephen 
Published: November 2021

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis and chemotherapy with gemcitabine has limited effects and is associated with development of drug resistance. Treatment of Panc1 and MiaPaca2 pancreatic cancer cells with gemcitabine induced expression of the orphan nuclear receptor 4A2 (NURR1) and analysis of The Cancer Genome Atlas indicated the NURR1 is overexpressed in pancreatic tumors and is a negative prognostic factor for patient survival. Results of NURR1 knockdown or treatment with the NURR1 antagonist 1,1-bis(3΄-indolyl)-1-(p-chlorophenyl)methane (C-DIM 12) demonstrated that NURR1 was prooncogenic in pancreatic cancer cells and regulated cancer cell and tumor growth and survival. NURR1 is induced by gemcitabine and serves as a key drug resistance factor and is also required for gemcitabine-induced cytoprotective autophagy. NURR1-regulated genes were determined by RNA sequencing of mRNAs expressed in MiaPaCa2 cells expressing NURR1 and in CRISPR/Cas9 gene–edited cells for NURR1 knockdown and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the differentially expressed genes showed that autophagy was the major pathway regulated by NURR1. Moreover, NURR1 regulated expression of two major autophagic genes, ATG7 and ATG12, which are also overexpressed in pancreatic tumors and like NURR1 are negative prognostic factors for patient survival. Thus, gemcitabine-induced cytoprotective autophagy is due to the NURR1–ATG7/ATG12 axis and this can be targeted and disrupted by NURR1 antagonist C-DIM12 demonstrating the potential clinical applications for combination therapies with gemcitabine and NURR1 antagonists.

Significance:
Gemcitabine induces NURR1-dependent ATG7 and ATG12 cytoprotective autophagy in PDA cells that can be reversed by NURR1 antagonists.
Identification of Functional Genetic Determinants of Cardiac Troponin T and I in a Multiethnic Population and Causal Associations With Atrial Fibrillation
Authors: Yang Yunju , Bartz Traci M. , Brown Michael R. , Guo Xiuqing , Zilhão Nuno R. , Trompet Stella , Weiss Stefan , Yao Jie , Brody Jennifer A. , Defilippi Christopher R. , Hoogeveen Ron C. , Lin Henry J. , Gudnason Vilmundur , Ballantyne Christie M. , Dörr Marcus , Jukema J. Wouter , Petersmann Astrid , Psaty Bruce M. , Rotter Jerome I. , Boerwinkle Eric , Fornage Myriam , Jun Goo , Yu Bing 
Published: November 2021

Background:
Elevated cardiac troponin levels in blood are associated with increased risk of cardiovascular diseases and mortality. Cardiac troponin levels are heritable, but their genetic architecture remains elusive.

Methods:
We conducted a transethnic genome-wide association analysis on high-sensitivity cTnT (cardiac troponin T; hs-cTnT) and high-sensitivity cTnI (cardiac troponin I; hs-cTnI) levels in 24 617 and 14 336 participants free of coronary heart disease and heart failure from 6 population-based cohorts, followed by a series of bioinformatic analyses to decipher the genetic architecture of hs-cTnT and hs-cTnI.

Results:

We identified 4 genome-wide significant loci for hs-cTnT including a novel locus rs3737882 in
PPFIA4
and 3 previously reported loci at
NCOA2
,
TRAM1
, and
BCL2
. One known locus at
VCL
was replicated for hs-cTnI. One copy of C allele for rs3737882 was associated with a 6% increase in hs-cTnT levels (minor allele frequency, 0.18;
P
=2.80×10
−9
). We observed pleiotropic loci located at
BAG3
and
ANO5
. The proportions of variances explained by single-nucleotide polymorphisms were 10.15% and 7.74% for hs-cTnT and hs-cTnI, respectively. Single-nucleotide polymorphisms were colocalized with
BCL2
expression in heart tissues and hs-cTnT and with
ANO5
expression in artery, heart tissues, and whole blood and both troponins. Mendelian randomization analyses showed that genetically increased hs-cTnT and hs-cTnI levels were associated with higher odds of atrial fibrillation (odds ratio, 1.38 [95% CI, 1.25–1.54] for hs-cTnT and 1.21 [95% CI, 1.06–1.37] for hs-cTnI).

Conclusions:
We identified a novel genetic locus associated with hs-cTnT in a multiethnic population and found that genetically regulated troponin levels were associated with atrial fibrillation.
A View from Inside: Understanding Puerto Rico Cockfighting
Authors: Aragunde-Kohl Úrsula A. , Segarra-González Yahaira , Meléndez-Samó Liza M. , Hernández-Rivera Ivemarie , Quiles-Peña Carolina 
Published: November 2021

Abstract
The purpose of this research was to better understand the beliefs and practices that the residents of Puerto Rico have regarding cockfighting, including their perception of the recently passed prohibition against nonhuman animal fighting on the island. It had an exploratory descriptive design consisting of three phases, where the qualitative data obtained from phase one would guide the process of identifying variables that could be measured. In the second phase, an instrument was developed, and in the third, it was administered. Most of the participants agreed with the prohibition of cockfighting in Puerto Rico and that it was necessary. The data showed that there is a disconnect between what the federal government of the United States legislated, what the local government and agencies that were supposed to enforce the prohibition did with the legislation, and what the people directly affected by the legislation received for education and guidance.
African Traditional Religion and Trans-Saharan Migration from Ghana
Authors: Tweneboah Seth , Agyeman Edmond Akwasi 
Published: November 2021

Abstract
This paper interrogates an unexamined component of the religion-migration nexus in Ghana. Using African Traditional Religion as a case in point, the paper examines the function shrines play in sustaining youth migration to Libya and across the Mediterranean to Europe. The paper relies on interviews and fieldtrips to migrant sending communities in the Nkoranza area of the Bono East region of central Ghana. The paper gives an account of the daily realities of prospective migrants, returnees and their families. Among other key findings, it is shown that there is an intricate connection between youth migration, the family system and the deities in sustaining the trans-Saharan migration. This migration, we observe, has become a livelihood strategy, the perpetuation of which reassures the survival of not only the people, but their gods as well.
“We Are Suffering Here”
Authors: Bedert Maarten 
Published: November 2021

Abstract
Liberia is a state built on a history of migration. From the transatlantic slave trade to its contemporary generation of transnational citizens, images of elsewhere have always informed this West African country’s local and national discussions of integration and exclusion. This paper shows how historical imaginations and representations of ‘here’ and ‘there’, of ‘suffering’ and ‘escape’, inform contemporary discourses of belonging in Liberia. I argue that the imagination of civilisation – kwii – and distinction plays an important role in the ways distance and mobility are perceived and articulated, both from a physical point of view and a moral-social point of view, at transnational and local levels. Rather than being merely tied to a national elite, the imagination of mobility is, I demonstrate, linked to an ethos of suffering articulated at all levels of society, informed by the experience of structural violence and crises over time.
Surgical and Oncologic Outcomes With Intraoperative Radiation Therapy for Early Breast Cancer
Authors: Friedman-Eldar Orli , Layton Christina , De Castro Silva Iago , Moller Mecker G , Allen Ahkeel , Franceschi Dido , Isrow Derek , Samuels Stuart , Takita Cristiane , Avisar Eli 
Published: November 2021

Background For selected patients with early-stage breast cancer (BC), intraoperative radiation therapy (IORT) has emerged as a convenient alternative to standard whole breast irradiation (WBI). We report a single institution experience with IORT in terms of oncologic outcomes, toxicities, and cosmesis. Methods Clinicopathological and perioperative outcomes of patients who underwent IORT for early-stage BC at a public hospital from 2017 to 2020 were retrospectively retrieved. Toxicity was categorized to acute or chronic based on 6 months post-IORT cutoff. Results 85 patients underwent IORT and had complete data, aged 49‐85 years (mean 62). Intraoperative radiation therapy added 23 minutes on average to the total operative time. Final stage was 0, I, and II in 40%, 58.9%, and 1.1% of patients, respectively. Mean tumor size was 0.8 cm (range .1-2.1), with ductal histology comprising 94% of cases. Surgical margins were positive in 2 patients, and adjuvant WBI was required in 5 patients. After a median follow‐up of 17 months (range 3-41), none of the patients had local recurrence and no mortality was recorded. Early wound complications included wound dehiscence (n = 1), seroma/hematoma (n = 15), and re-operation with loss of nipple-areola complex (n = 1). Chronic skin toxicities were reported in 10 (12%) patients and good or excellent cosmetic outcome was reported in 93% of patients. Conclusions Utilizing IORT among low-risk early BC patients may be a safe and more convenient alternative to traditional WBI, with low toxicity rate, acceptable cosmetic results, and good oncologic outcomes at 17 months. Longer follow-up and further prospective controlled studies are needed to confirm these findings.
Near Disappearance of Splenorrhaphy as an Operative Strategy for Splenic Preservation After Trauma
Authors: Ko Ara , Radding Sydney , Feliciano David V. , DuBose Joseph J. , Kozar Rosemary A. , Morrison Jonathan , Kundi Rishi , Maddox John , Scalea Thomas M. 
Published: November 2021

Background Splenorrhaphy was once used to achieve splenic preservation in up to 40% of splenic injuries. With increasing use of nonoperative management and angioembolization, operative therapy is less common and splenic injuries treated operatively are usually high grade. Patients are often unstable, making splenic salvage unwise. Modern surgeons may no longer possess the knowledge to perform splenorrhaphy. Methods The records of adult trauma patients with splenic injuries from September 2014 to November 2018 at an urban level I trauma center were reviewed retrospectively. Data including American Association for the Surgery of Trauma splenic organ injury scale, type of intervention, splenorrhaphy technique, and need for delayed splenectomy were collected. This contemporary cohort (CC) was compared to a historical cohort (HC) of splenic injuries at a single center from 1980 to 1989 (Ann Surg 1990; 211: 369). Results From 2014 to 2018, 717 adult patients had splenic injuries. Initial management included 157 (21.9%) emergent splenectomy, 158 (22.0%) angiogram ± embolization, 371 (51.7%) observation, and only 10 (1.4%) splenorrhaphy. The HC included a total of 553 splenic injuries, of which 313 (56.6%) underwent splenectomy, while splenorrhaphy was performed in 240 (43.4%). Those who underwent splenorrhaphy in each cohort (CC vs HC) were compared. Conclusion The success rate of splenorrhaphy has not changed. However, splenorrhaphy now involves only electrocautery with topical hemostatic agents and is used primarily in low-grade injuries. Suture repair and partial splenectomy seem to be “lost arts” in modern trauma care.
Early Versus Delayed Microdiscectomy for Chronic Sciatica Lasting 4–12 Months Secondary to Lumbar Disc Herniation: A Secondary Analysis of a Randomized Controlled Trial
Authors: Bailey Christopher S. , Glennie Andrew , Rasoulinejad Parham , Kanawati Andrew , Taylor David , Sequeira Keith , Miller Thomas , Watson Jim , Rosedale Richard , Bailey Stewart I. , Gurr Kevin R. , Siddiqi Fawaz , Urquhart Jennifer C. 
Published: November 2021

Objectives To compare the effect of delaying surgery on clinical outcome in patients with chronic sciatica secondary to lumbar disc herniation. Methods Patients with sciatica lasting 4–12 months and lumbar disc herniation at the L4–L5 or L5–S1 level were randomized to undergo microdiscectomy (early surgery) or to receive 6 months of nonoperative treatment followed by surgery if needed (delayed surgery). Outcomes were leg pain, Oswestry Disability Index score (ODI), back pain, SF–36 physical component (PCS) and mental component (MCS) summary scores, employment, and satisfaction measured preoperatively and at 6 weeks, 3 months, 6 months, and 1 year after surgery. Results Of the 64 patients in the early surgery group, 56 underwent microdiscectomy an average of 3 ± 2 weeks after enrollment. Of the 64 patients randomized to nonoperative care, 22 patients underwent delayed surgery an average of 53 ± 24 weeks after enrollment. The early surgery group experienced less leg pain than the delayed surgery group, which was the primary outcome, at 6 months after surgery (early surgery 2.8 ± .4 vs delayed surgery 4.8 ± .7; difference, 2.0; 95% confidence interval, .5–3.5). The overall estimated mean difference between groups significantly favored early surgery for leg pain, ODI, SF36-PCS, and back pain. The adverse event rate was similar between groups. Conclusions Patients presenting with chronic sciatica treated with delayed surgery after prolonging standardized non-operative care have inferior outcomes compared to those that undergo expedited surgery.
Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation
Authors: Sparreman Mikus Maria , Kolmert Johan , Andersson Lars I. , Östling Jörgen , Knowles Richard G. , Gómez Cristina , Ericsson Magnus , Thörngren John-Olof , Emami Khoonsari Payam , Dahlén Barbro , Kupczyk Maciej , De Meulder Bertrand , Auffray Charles , Bakke Per S. , Beghe Bianca , Bel Elisabeth H. , Caruso Massimo , Chanez Pascal , Chawes Bo , Fowler Stephen J. , Gaga Mina , Geiser Thomas , Gjomarkaj Mark , Horváth Ildikó , Howarth Peter H. , Johnston Sebastian L. , Joos Guy , Krug Norbert , Montuschi Paolo , Musial Jacek , Niżankowska-Mogilnicka Ewa , Olsson Henric K. , Papi Alberto , Rabe Klaus F. , Sandström Thomas , Shaw Dominick E. , Siafakas Nikolaos M. , Uhlén Mathias , Riley John H. , Bates Stewart , Middelveld Roelinde J.M. , Wheelock Craig E. , Chung Kian Fan , Adcock Ian M. , Sterk Peter J. , Djukanovic Ratko , Nilsson Peter , Dahlén Sven-Erik , James Anna 
Published: November 2021

RationaleAsthma phenotyping requires novel biomarker discovery.ObjectivesTo identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs).MethodsAn antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED.ResultsIn U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SAversusMMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-β and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation.ConclusionsThe plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA.
External validation of a refined four-stratum risk assessment score from the French pulmonary hypertension registry
Authors: Boucly Athénaïs , Weatherald Jason , Savale Laurent , de Groote Pascal , Cottin Vincent , Prévot Grégoire , Chaouat Ari , Picard François , Horeau-Langlard Delphine , Bourdin Arnaud , Jutant Etienne-Marie , Beurnier Antoine , Jevnikar Mitja , Jaïs Xavier , Simonneau Gérald , Montani David , Sitbon Olivier , Humbert Marc 
Published: November 2021

IntroductionContemporary risk assessment tools categorise patients with pulmonary arterial hypertension (PAH) as low, intermediate or high risk. A minority of patients achieve low risk status with most remaining intermediate risk. Our aim was to validate a four-stratum risk assessment approach categorising patients as low, intermediate-low, intermediate-high or high risk, as proposed by the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) investigators.MethodsWe evaluated incident patients from the French PAH Registry and applied a four-stratum risk method at baseline and at first reassessment. We applied refined cut-points for three variables: World Health Organization functional class, 6-min walk distance and N-terminal pro-brain natriuretic peptide. We used Kaplan–Meier survival analyses and Cox proportional hazards regression to assess survival according to three-stratum and four-stratum risk approaches.ResultsAt baseline (n=2879), the four-stratum approach identified four distinct risk groups and performed slightly better than a three-stratum method for predicting mortality. Four-stratum model discrimination was significantly higher than the three-stratum method when applied during follow-up and refined risk categories among subgroups with idiopathic PAH, connective tissue disease-associated PAH, congenital heart disease and portopulmonary hypertension. Using the four-stratum approach, 53% of patients changed risk category from baseline compared to 39% of patients when applying the three-stratum approach. Those who achieved or maintained a low risk status had the best survival, whereas there were more nuanced differences in survival for patients who were intermediate-low and intermediate-high risk.ConclusionsThe four-stratum risk assessment method refined risk prediction, especially within the intermediate risk category of patients, performed better at predicting survival and was more sensitive to change than the three-stratum approach.