bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enkurin domain containing 1 (ENKD1) regulates the proliferation, migration and invasion of non‐small cell lung cancer cells
Authors: Song Ting , Zhou Peng , Sun Chunjiao , He Na , Li Haixia , Ran Jie , Zhou Jun , Wu Yue , Liu Min 
Published: March 2021

AbstractNon‐small cell lung cancer (NSCLC) is the most common cause of cancer mortality worldwide. NSCLC has an aggressive phenotype and poor prognosis, and is quite heterogeneous without effective and specific targeted therapies. Therefore, exploring new tumor markers and drug targets for NSCLC is crucial towards individualized treatment. Here, we demonstrate that enkurin domain containing 1 (ENKD1), a protein with unknown structure and function, is significantly downregulated in NSCLC tumor tissues compared with their non‐tumor counterparts. We also show that ENKD1 expression is decreased in NSCLC cells compared to normal human lung epithelial cells. EdU incorporation, wound healing, and transwell invasion assays reveal that ENKD1 regulates the proliferation, migration, and invasion of NSCLC cells. Collectively, these results suggest that ENKD1 plays an important role in NSCLC progression and that ENKD1 is a tumor marker and a potential molecular drug target for the treatment of NSCLC patients.
IgE‐cross‐blocking antibodies to Fagales following sublingual immunotherapy with recombinant Bet v 1
Authors: Grilo João Rodrigues , Kitzmüller Claudia , Aglas Lorenz , Sánchez Acosta Gabriela , Vollmann Ute , Ebner Christof , Horak Fritz , Kinaciyan Tamar , Radauer Christian , Ferreira Fatima , Jahn‐Schmid Beatrice , Bohle Barbara 
Published: March 2021

AbstractBackgroundEvidence has accumulated that birch pollen immunotherapy reduces rhinoconjunctivitis to pollen of birch homologous trees. Therapeutic efficacy has been associated with IgE‐blocking IgG antibodies. We have recently shown that sera collected after 16 weeks of sublingual immunotherapy with recombinant Bet v 1 (rBet v 1‐SLIT) display strong IgE‐blocking bioactivity for Bet v 1. Here, we assessed whether rBet v 1‐SLIT‐induced IgG antibodies display cross‐blocking activity to related allergens in Fagales pollen.MethodsIgE, IgG1 and IgG4 reactivity to recombinant Bet v 1, Aln g 1, Car b 1, Ost c 1, Cor a 1, Fag s 1, Cas s 1 and Que a 1 were assessed in pre‐ and post‐SLIT samples of 17 individuals by ELISA. A basophil inhibition assay using stripped basophils re‐sensitized with a serum pool containing high Bet v 1‐specific IgE levels was established and used to assess CD63 expression in response to allergens after incubation with pre‐SLIT or post‐SLIT samples. IgG1 and IgG4 were depleted from post‐SLIT samples to assess its contribution to IgE‐cross‐blocking.ResultsSublingual immunotherapy with recombinant Bet v 1 boosted cross‐reactive IgE antibodies and induced IgG1 and IgG4 antibodies with inter‐ and intra‐individually differing reactivity to the homologs. Highly variable cross‐blocking activities of post‐SLIT samples to the different allergens were found. IgG1 and IgG4 antibodies displayed cross‐blocking activity with individual variance.ConclusionsOur mechanistic approach suggested that immunotherapy with the reference allergen Bet v 1 induces individual repertoires of cross‐reactive IgG1 and IgG4 antibodies. The cross‐blocking bioactivity of these antibodies was also highly variable and neither predictable from protein homology nor IgE‐cross‐reactivity.
Population‐based picture of breast reconstruction in Queensland, Australia
Authors: Youl Philippa , Philpot Shoni , Moore Julie , Theile David E. 
Published: March 2021

AbstractBackgroundApproximately 40% of women with invasive breast cancer will undergo a mastectomy. Clinical practice guidelines recommend breast reconstruction (BR) options should be discussed with all women who are to undergo a mastectomy. We sought to examine rates of BR, BR methods over time and to identify factors associated with the likelihood of receiving BR in Queensland.MethodsThis population‐based study used linked data from the Queensland Oncology Repository for 12 364 women who underwent a mastectomy for invasive breast cancer from 2008 to 2017. Multivariate logistic regression was used to model predictors of immediate breast reconstruction (IBR) and delayed breast reconstruction (DBR).ResultsOverall, 2560 (20.7%) women had BR, with 9.8% having IBR and 10.9% having DBR. Factors associated with a reduced likelihood of IBR or DBR included older age (P < 0.001), living in a regional/rural area (P < 0.001) and having a mastectomy in a public versus private hospital (P < 0.001). Median time from mastectomy to DBR was 18.4 and 29.2 months for women attending a private versus public hospital, respectively (P < 0.001). Use of implant‐based BR increased significantly with a corresponding decrease in autologous BR over time.ConclusionsSignificant disparities exist in rates of BR between public and private hospitals. Women living in regional and rural areas as well as those aged over 60 years continue to have lower rates of BR. Addressing the health system barriers and developing strategies to improve access to, and uptake of BR should be a priority.
Holiday hazards: burns in children during school holidays
Authors: Tran Sonia , Holland Andrew J. A. , Bertinetti Monique 
Published: March 2021

AbstractBackgroundPaediatric burns are preventable injuries that can have a permanent impact on a child's health and wellbeing. The Burns Unit at the Children's Hospital at Westmead appeared to experience an increase in paediatric burn injury referrals during the school holidays. The evaluation of the characteristics of burn injuries in the school holidays compared to the school term may improve the effectiveness of burn prevention programmes.MethodsA retrospective review was performed of all school‐aged children who were referred to our institution between January 2005 and January 2019. Patient details, burn aetiology, burn severity, length of stay and need for grafting were compared between burns sustained during the school holidays and burns sustained during school term.ResultsA total of 3020 children were referred to Children's Hospital at Westmead between January 2005 and January 2019. The mean number of burns sustained increased from 3.8 children per week during the school term to 5.4 children per week during school holidays (P < 0.0001). Contact burns were proportionally more common during school holidays than during the school term (26% versus 19.7%, P < 0.0001), whilst the proportion of scalds decreased significantly during the school holidays (43.5 versus 51.4%, P < 0.0001). There was no difference between mean age, % total body surface area, admission rates, length of stay or skin grafting rates.ConclusionThere is a significant increase in burn injuries among school‐aged children during the school holidays. This highlights the need for targeted education and prevention campaigns in the periods immediately preceding the school holidays.
The Dialectic of Neoliberal Exploitation and Cultural‐Sexual Exclusion: From Special Economic Zones to LGBT‐Free Zones in Poland
Authors: Żuk Piotr , Pluciński Przemysław , Żuk Paweł 
Published: March 2021

AbstractThis article analyses the process of spatial segregation in Poland: the transition from economic deprivation and the neoliberal logic initiated in the 1990s, which can be symbolised by special economic zones, to the atmosphere of cultural exclusion manifested by LGBT‐free zones created at the level of municipalities, cities and regions in Poland in 2019 and 2020. The authors defend the thesis that events in Poland have confirmed that not only the state can be authoritarian, but that local and regional authorities can also reproduce an authoritarian and excluder vision of social order. The article also shows similarities between the arguments of the modern populist right, which demanded the establishment of LGBT‐free zones, and anti‐Semitic slogans of the pre‐war (1918–1939) right, which demanded the creation of ghettos for Jews. In conclusion, the authors call for avoiding the mistake of separating economic exclusion from cultural discrimination and treating these challenges separately.
Development of enzyme immunoassay for chromogranin A (CgA) and profiling of plasma CgA concentrations in the cow
Authors: Saito Chihiro , Ido‐Matsumoto Haruka , Kumazaki Hiromasa , Kubo Tomoaki , Kanazawa Tomomi , Takahashi Toru 
Published: March 2021

AbstractThe objectives of this study were to establish and characterize a homologous immunoassay for bovine chromogranin A (bCgA) and to profile plasma bCgA concentrations during early pregnancies. We synthesized oligopeptide corresponding to the amino acid sequence 341–355 of bCgA for immunizing rabbits and peptide corresponding to the amino acid sequence 336–365 of bCgA for both a biotinylated tracer and reference standards. Recombinant bCgA protein was also generated inEscherichia colilysate. Dose‐dependent displacement curves were obtained from 1 to 1,000 nM of the reference standards. The displacement curves showed a good relationship between the reference standards of the synthetic peptide and the serially diluted plasma sample or recombinant bCgA protein generated in the present study. The assay sensitivity defined as the value of two standard deviations below the zero standard was calculated as 0.46 nM. The intraassay and interassay coefficients of variation were 6.48% and 13.4%, respectively. Changes in the plasma bCgA concentrations in early pregnancies undulated in nonpregnant animals. The results of the present study suggest that assaying plasma bCgA concentrations could be utilized as measures to evaluate the physiological status of cattle.
Adverse events of recreational cannabis use reported to the French addictovigilance network (2012–2017)
Authors: Bouquet Emilie , Pain Stéphanie , Eiden Céline , Jouanjus Emilie , Richard Nathalie , Fauconneau Bernard , Pérault‐Pochat Marie‐Christine ,   French Addictovigilance Network
Published: March 2021

AimsTo describe the adverse events (AEs) of recreational cannabis use in France between 2012 and 2017.MethodsAEs related to recreational cannabis use, alone or in combination with alcohol and/or tobacco reported to the French Addictovigilance Network were analysed (excluding cannabidiol and synthetic cannabinoids).ResultsReporting of AEs tripled between 2012 (n = 179, 6.3%, 95% confidence interval [CI] = 5.4–7.2) and 2017 (n = 562, 10.1%, 95% CI = 9.3–10.9), reaching 2217 cases. They concerned mainly men (76.4%) and users aged between 18 and 34 years (18–25: 30.9%; 26–34: 26.3%, range: 12–84 years). Cannabis was mainly inhaled (71.6%) and exposure was most often chronic (64.2%). Many types of AEs were reported: psychiatric (51.2%), neurological (15.6%), cardiac (7.8%) and gastrointestinal (7.7%), including unexpected AEs (n = 34, 1.1%). The most common effect was dependence, ranging from 10.1% (95% CI = 7.9–12.3) to 20.3% (95% CI = 17.3–23.2) over the study period. Cannabinoid hyperemesis syndrome (n = 87, 2.8%) emerged from 2015. Deaths accounted for 0.2% of all AEs (4 men and 3 women aged on average 35 years). A chronic pattern of cannabis use was reported in 4 of them (intracranial hypertension in the context of lung cancer, suicide, cerebral haematoma, neonatal death with concomitant chronic alcohol use), while in the other cases the toxicological analysis identified cannabis use (ruptured aneurysm and unknown aetiology).ConclusionThis study showed a multitude of AEs related to recreational cannabis use, including unexpected AEs and deaths. It highlights the problem of dependence and the emergence of cannabinoid hyperemesis syndrome.
Vasculo‐toxic and pro‐inflammatory action of unbound haemoglobin, haem and iron in transfusion‐dependent patients with haemolytic anaemias
Authors: Vinchi Francesca , Sparla Richard , Passos Sara T. , Sharma Richa , Vance S. Zebulon , Zreid Hala S. , Juaidi Hesham , Manwani Deepa , Yazdanbakhsh Karina , Nandi Vijay , Silva André M. N. , Agarvas Anand R. , Fibach Eitan , Belcher John D. , Vercellotti Gregory M. , Ghoti Husam , Muckenthaler Martina U. 
Published: March 2021

SummaryIncreasing evidence suggests that free haem and iron exert vasculo‐toxic and pro‐inflammatory effects by activating endothelial and immune cells. In the present retrospective study, we compared serum samples from transfusion‐dependent patients with β‐thalassaemia major and intermedia, hereditary spherocytosis and sickle cell disease (SCD). Haemolysis, transfusions and ineffective erythropoiesis contribute to haem and iron overload in haemolytic patients. In all cohorts we observed increased systemic haem and iron levels associated with scavenger depletion and toxic ‘free’ species formation. Endothelial dysfunction, oxidative stress and inflammation markers were significantly increased compared to healthy donors. In multivariable logistic regression analysis, oxidative stress markers remained significantly associated with both haem‐ and iron‐related parameters, while soluble vascular cell adhesion molecule 1 (sVCAM‐1), soluble endothelial selectin (sE‐selectin) and tumour necrosis factor α (TNFα) showed the strongest association with haem‐related parameters and soluble intercellular adhesion molecule 1 (sICAM‐1), sVCAM‐1, interleukin 6 (IL‐6) and vascular endothelial growth factor (VEGF) with iron‐related parameters. While hereditary spherocytosis was associated with the highest IL‐6 and TNFα levels, β‐thalassaemia major showed limited inflammation compared to SCD. The sVCAM1 increase was significantly lower in patients with SCD receiving exchange compared to simple transfusions. The present results support the involvement of free haem/iron species in the pathogenesis of vascular dysfunction and sterile inflammation in haemolytic diseases, irrespective of the underlying haemolytic mechanism, and highlight the potential therapeutic benefit of iron/haem scavenging therapies in these conditions.
Animal models of pulmonary hypertension: Getting to the heart of the problem
Authors: Dignam Joshua P. , Scott Tara E. , Kemp‐Harper Barbara K. , Hobbs Adrian J. 
Published: March 2021

Despite recent therapeutic advances, pulmonary hypertension (PH) remains a fatal disease due to the development of right ventricular (RV) failure. At present, no treatments targeted at the right ventricle are available, and RV function is not widely considered in the preclinical assessment of new therapeutics. Several small animal models are used in the study of PH, including the classic models of exposure to either hypoxia or monocrotaline, newer combinational and genetic models, and pulmonary artery banding, a surgical model of pure RV pressure overload. These models reproduce selected features of the structural remodelling and functional decline seen in patients and have provided valuable insight into the pathophysiology of RV failure. However, significant reversal of remodelling and improvement in RV function remains a therapeutic obstacle. Emerging animal models will provide a deeper understanding of the mechanisms governing the transition from adaptive remodelling to a failing right ventricle, aiding the hunt for druggable molecular targets.LINKED ARTICLESThis article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc
Non‐peptide agonists and positive allosteric modulators of glucagon‐like peptide‐1 receptors: Alternative approaches for treatment of Type 2 diabetes
Authors: Malik Faisal , Li Zhijun 
Published: March 2021

Glucagon‐like peptide‐1 (GLP‐1) receptors belong to the pharmaceutically important Class B family of GPCRs and are involved in many biologically significant signalling pathways. Its incretin peptide ligand GLP‐1 analogues are effective treatments for Type 2 diabetes. Although developing non‐peptide low MW drugs targeting GLP‐1 receptors remains elusive, considerable progress has been made in discovering non‐peptide agonists and positive allosteric modulators (PAMs) of GLP‐1 receptors with demonstrated efficacy. Many of these compounds induce biased signalling in GLP‐1 receptor‐mediated functional pathways. High‐quality structures of GLP‐1 receptors in both inactive and active states have been reported, revealing detailed molecular interactions between GLP‐1 receptors and non‐peptide agonists or PAMs. These progresses raise the exciting possibility of developing non‐peptide drugs of GLP‐1 receptors as alternative treatments for Type 2 diabetes. The insight into the interactions between the receptor and the non‐peptide ligand is also useful for developing non‐peptide ligands targeting other Class B GPCRs.LINKED ARTICLESThis article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc
Exempted sectors in free trade agreements
Authors: Deardorff Alan V. , Sharma Rishi R. 
Published: March 2021

AbstractAlmost all participants in free trade agreements (FTAs) exclude at least a few products or sectors from complete tariff removal on the exports of their FTA partners. The positive tariffs that remain within an FTA are often the highest tariffs that the countries apply on an MFN basis. It seems plausible that such exclusions may be chosen because the domestic producers of these products are viewed as especially vulnerable to competition from imports from the partner country. In brief, they are especially “sensitive sectors.” We develop this idea theoretically and then test it empirically on data from 37 countries in 240 importer–exporter pairs within FTAs. We find support for the sensitive‐sector hypothesis only in the high‐income countries. We find that low‐income countries, in contrast, exempt sectors where bilateral tariff removal would be more likely trade‐diverting and therefore harmful. Our explanation for this, supported empirically, is not that they are following the advice of trade economists, but rather that they are avoiding loss of tariff revenue and may also perhaps be influenced by the greater bargaining power of richer and/or larger partners in their FTAs.
The evaluation of follow‐up strategies of watch‐and‐wait patients with a complete response after neoadjuvant therapy in rectal cancer
Authors: Haak Hester E. , Žmuc Jan , Lambregts Doenja M. J. , Beets‐Tan Regina G. H. , Melenhorst Jarno , Beets Geerard L. , Maas Monique ,   the Dutch Watch‐and‐Wait Consortium
Published: March 2021

ABSTRACTAimMany of the current follow‐up schedules in a watch‐and‐wait approach include very frequent MRI and endoscopy examinations to ensure early detection of local regrowth (LR). The aim of this study was to analyse the occurrence and detection of LR in a watch‐and‐wait cohort and to suggest a more efficient follow‐up schedule.MethodRectal cancer patients with a clinical complete response after neoadjuvant therapy were prospectively and retrospectively included in a multicentre watch‐and‐wait registry between 2004 and 2018, with the current follow‐up schedule with 3‐monthly endoscopy and MRI in the first year and 6 monthly thereafter. A theoretical comparison was constructed for the detection of LR in the current follow‐up schedule against four other hypothetical schedules.ResultsIn all, 50/304 (16%) of patients developed a LR. The majority (98%) were detected at ≤2 years, located in the lumen (94%) and were visible on endoscopy (88%). The theoretical comparison of the different hypothetical schedules suggests that the optimal follow‐up schedule should focus on the first 2 years with 3‐monthly endoscopy and 3–6 monthly MRI. Longer intervals in the first 2 years will cause delays in diagnosis of LR ranging from 0 to 5 months. After 2 years, increasing the interval from 6 to 12 months did not cause important delays.ConclusionThe optimal follow‐up schedule for a watch‐and‐wait policy in patients with a clinical complete response after chemoradiation for rectal cancer should include frequent endoscopy and to a lesser degree MRI in the first 2 years. Longer intervals, up to 12 months, can be considered after 2 years.
Ant colony optimization–evolutionary hybrid optimization with translation of problem representation
Authors: Polnik Wojciech , Stobiecki Jacek , Byrski Aleksander , Kisiel‐Dorohinicki Marek 
Published: March 2021

AbstractDifferent hybrid optimization metaheuristics (see the works of Talbi for classification) either assume the embedding of one algorithm (usually a metaheuristic) in another (for instance, a local search inside an evolutionary algorithm—a memetic algorithm) or creating a chain of algorithms. In this paper, such a chain combination of two algorithms (namely, the Ant Colony Optimization and Evolutionary Algorithm) is presented. However, because of the intrinsic differences between the two algorithms (a vector of labels and a pheromone table when solving the traveling salesman problem, for example), several dedicated algorithms for translating the solutions between these two representations of the problem are proposed. The hybrid algorithm constructed with the application of the translation methods turns out to be significantly better in solving the TSP compared to non‐hybrid versions (relevant experimental results are presented and discussed). This paves the way for new possibilities of constructing hybrid metaheuristics by putting together completely different ones (using different representations); the impact of the presented research is aimed far beyond the hybridization of only ant colony optimization and evolutionary algorithm.
Kant, Frege, and the normativity of logic:MacFarlane's argument for common ground
Authors: Nunez Tyke 
Published: March 2021

AbstractAccording to what used to be the standard view (Poincaré, Wang, etc.), although Frege endorses, and Kant denies, the claim that arithmetic is reducible to logic, there is not a substantive disagreement between them because their conceptions of logic are too different. In his “Frege, Kant, and the Logic in Logicism,” John MacFarlane aims to establish that Frege and Kant do share enough of a conception of logic for this to be a substantive, judicable dispute. MacFarlane maintains that for both Frege and Kant, the fundamental defining characteristic of logic is “that it provides norms for thoughtas such” (MacFarlane, 2002, p.57). I defend the standard view. I show that MacFarlane's argument rests on conflating the way that pure general logic is normative as a canon and as a propaedeutic, and that once these are distinguished the argument is blocked.