bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real‐world Omalizumab and Mepolizumab treated difficult asthma phenotypes and their clinical outcomes
Authors: Fong Wei Chern Gavin , Azim Adnan , Knight Deborah , Mistry Heena , Freeman Anna , Felongco Mae , Kyyaly Aref , Harvey Matthew , Dennison Patrick , Zhang Hongmei , Howarth Peter , Arshad Syed Hasan , Kurukulaaratchy Ramesh J. 
Published: April 2021

AbstractBackgroundOmalizumab and Mepolizumab are biologic drugs with proven efficacy in clinical trials. However, a better understanding of their real‐world effectiveness in severe asthma management is needed.ObjectivesTo better understand the real‐world effectiveness of Omalizumab and Mepolizumab, elucidate the clinical phenotypes of patients treated with these drugs, identify baseline characteristics associated with biologic response and assess the spectrum of responses to these medications.MethodsUsing real‐world clinical data, we retrospectively phenotyped biologic naïve patients from the Wessex AsThma CoHort of difficult asthma (N = 478) commenced on Omalizumab (N = 105) or Mepolizumab (N = 62) compared to severe asthma patients not receiving biologics (SNB, N = 178). We also assessed multiple clinical endpoints and identified features associated with response.ResultsCompared to SNB, Omalizumab patients were younger, diagnosed with asthma earlier, and more likely to have rhinitis. Conversely, compared to SNB, Mepolizumab patients were predominantly older males, diagnosed with asthma later, and more likely to have nasal polyposis but less dysfunctional breathing. Both treatments reduced exacerbations, Acute Healthcare Encounters [AHE] (emergency department or hospital admissions), maintenance oral corticosteroid dose, and improved Asthma Control Questionnaire 6 (ACQ6) scores. Omalizumab response was independently associated with more baseline exacerbations (p = .024) but fewer AHE (p = .050) and absence of anxiety (p = .008). Lower baseline ACQ6 was independently associated with Mepolizumab response (p = .007). A composite group of non‐responders demonstrated significantly more psychopathologies and worse baseline subjective disease compared to responder groups.Conclusions and Clinical RelevanceIn a difficult asthma cohort, Omalizumab and Mepolizumab were used in distinct clinical phenotypes but were both multidimensionally efficacious. Certain baseline clinical characteristics were associated with poorer biologic responses, such as psychological co‐morbidity, which may assist clinicians in biologic selection. These characteristics also emphasize the need for comprehensive approaches to support these patients.
Functional variants in the chromosome 4q21 locus contribute to allergic rhinitis risk by modulating the expression of N‐acylethanolamine acid amidase
Authors: Sio Yang Yie , Shi Ping , Say Yee‐How , Chew Fook Tim 
Published: April 2021

AbstractBackgroundPrevious haplotype‐based association studies identified chromosome 4q21 as an allergic rhinitis (AR) susceptibility locus; however, the functional role of 4q21 single nucleotide polymorphisms (SNPs) on AR risk remains unclear.ObjectiveTo investigate the functional effect of 4q21 SNPs on AR risk by conducting cohort‐based functional genomics and genetic association analyses.MethodsThe associations between 4q21 SNPs and mRNA expression levels of three 4q21‐associated genes (SDAD1, NAAA and CXCL9) in peripheral blood mononuclear cells (PBMCs) were assessed in a Singapore/Malaysia Chinese cohort (n = 291). Exon expression levels of these genes in PBMCs were tested against the tag‐SNP genotypes in a Singapore Chinese cohort (n = 30). Serum protein levels of these genes were assessed with tag‐SNP genotypes in a Singapore Chinese cohort (n = 193). SNP functions were characterized through luciferase assay. In a Singapore Chinese cohort (n = 1794), we confirmed the associations between functional SNPs and AR.ResultsForty SNPs in 4q21 showed significant associations with NAAA (but not SDAD1 or CXCL9) mRNA expression in PBMCs, of which were tagged by two tag‐SNPs, rs17001237 and rs2242470. Both tag‐SNPs rs2242470 and rs12648687 (a proxy for rs17001237) were also significantly associated with the expression level of NAAA exon 1. Tag‐SNP rs12648687 was correlated with serum NAAA level. A four promoter SNPs‐haplotype tagged by rs17001237 influenced the NAAA promoter activity in HEK293T cells. Lastly, individuals carrying the risk allele A of rs12648687 exhibited significantly higher AR risk in the Singapore Chinese population.Conclusions & Clinical RelevanceThe rs17001237 linkage set SNPs in the 4q21 locus are associated with NAAA expression at both gene and protein levels ex vivo, have functional consequences in vitro and contribute to AR susceptibility in our study population. Our findings provided a better understanding of the genetic mechanism that contributes to AR pathogenesis.
Intracellular expression of granzymes A, B, K and M in blood lymphocyte subsets of critically ill patients with or without sepsis
Authors: García-Laorden M Isabel , Hoogendijk Arie J , Wiewel Maryse A , van Vught Lonneke A , Schultz Marcus J , Bovenschen Niels , de Vos Alex F , van der Poll Tom 
Published: April 2021

SummarySepsis is a complex syndrome related to an infection-induced exaggerated inflammatory response, which is associated with a high mortality. Granzymes (Gzm) are proteases mainly found in cytotoxic lymphocytes that not only have a role in target cell death, but also as mediators of infection and inflammation. In this study we sought to analyse the intracellular expression of GzmA, B, M and K by flow cytometry in diverse blood lymphocyte populations from 22 sepsis patients, 12 non-infected intensive care unit (ICU) patients and 32 healthy controls. Additionally, we measured GzmA and B plasma levels. Both groups of patients presented decreased percentage of natural killer (NK) cells expressing GzmA, B and M relative to healthy controls, while sepsis patients showed an increased proportion of CD8+ T cells expressing GzmB compared to controls. Expression of GzmK remained relatively unaltered between groups. Extracellular levels of GzmB were increased in non-infected ICU patients relative to sepsis patients and healthy controls. Our results show differential alterations in intracellular expression of Gzm in sepsis patients and non-infected critically ill patients compared to healthy individuals depending on the lymphocyte population and on the Gzm.
16α-Bromoepiandrosterone as a new candidate for experimental diabetes–tuberculosis co-morbidity treatment
Authors: López-Torres Manuel Othoniel , Marquina-Castillo Brenda , Ramos-Espinosa Octavio , Mata-Espinosa Dulce , Barrios-Payan Jorge A , Baay-Guzman Guillermina , Yepez Sara Huerta , Bini Estela , Torre-Villalvazo Ivan , Torres Nimbe , Tovar Armando , Chamberlin William , Ge Yu , Carranza Andrea , Hernández-Pando Rogelio 
Published: April 2021

Summary
Tuberculosis (TB) is the leading cause of death from a single bacterial infectious agent and is one of the most relevant issues of public health. Another pandemic disease is type II diabetes mellitus (T2D) that is estimated to affect half a billion people in the world. T2D is directly associated with obesity and a sedentary lifestyle and is frequently associated with immunosuppression. Immune dysfunction induced by hyperglycemia increases infection frequency and severity. Thus, in developing countries the T2D/TB co-morbidity is frequent and represents one of the most significant challenges for the health-care systems. Several immunoendocrine abnormalities are occurring during the chronic phase of both diseases, such as high extra-adrenal production of active glucocorticoids (GCs) by the activity of 11-β-hydroxysteroid dehydrogenase type 1 (11-βHSD1). 11-βHSD1 catalyzes the conversion of inactive cortisone to active cortisol or corticosterone in lungs and liver, while 11-β-hydroxysteroid dehydrogenase type 2 (11-βHSD2) has the opposite effect. Active GCs have been related to insulin resistance and suppression of Th1 responses, which are deleterious factors in both T2D and TB. The anabolic adrenal hormone dehydroepiandrosterone (DHEA) exerts antagonistic effects on GC signaling in immune cells and metabolic tissues; however, its anabolic effects prohibit its use to treat immunoendocrine diseases. 16α-bromoepiandrosterone (BEA) is a water miscible synthetic sterol related to DHEA that lacks an anabolic effect while amplifying the immune and metabolic properties with important potential therapeutic uses. In this work, we compared the expression of 11-βHSD1 and the therapeutic efficacy of BEA in diabetic mice infected with tuberculosis (TB) (T2D/TB) with respect to non-diabetic TB-infected mice (TB). T2D was induced by feeding mice with a high-fat diet and administering a single low-dose of streptozotocin. After 4 weeks of T2D establishment, mice were infected intratracheally with a high-dose of Mycobacterium tuberculosis strain H37Rv. Then, mice were treated with BEA three times a week by subcutaneous and intratracheal routes. Infection with TB increased the expression of 11-βHSD1 and corticosterone in the lungs and liver of both T2D/TB and TB mice; however, T2D/TB mice developed a more severe lung disease than TB mice. In comparison with untreated animals, BEA decreased GC and 11-βHSD1 expression while increasing 11-βHSD2 expression. These molecular effects of BEA were associated with a reduction in hyperglycemia and liver steatosis, lower lung bacillary loads and pneumonia. These results uphold BEA as a promising effective therapy for the T2D/TB co-morbidity.
Scleral necrosis after brachytherapy for uveal melanoma: Analysis of risk factors
Authors: Jabbarli Leyla , Guberina Maja , Biewald Eva , Flühs Dirk , Guberina Nika , Le Guin Claudia H. D. , Sauerwein Wolfgang , Bornfeld Norbert , Stuschke Martin , Bechrakis Nikolaos E. 
Published: April 2021

AbstractBackgroundRadiation‐induced scleral necrosis (RISN) is a rare, but a serious complication of brachytherapy for uveal melanoma. We aimed at analysing the incidence, timing and risk factors associated with development of RISN in a large institutional series.MethodsAll consecutive cases with brachytherapy for uveal melanoma treated by the Departments of Ophthalmology and Radiotherapy at University Hospital Essen between 1999 and 2016 were eligible. Development of RISN during the post‐treatment follow‐up was recorded. A 1:2 propensity score matched case–control study was performed for the evaluation of the prognostic value of different tumour‐ and treatment‐associated parameters.ResultsRISN was documented in 115 (2.9%) of 3960 patients with uveal melanoma included in the final analysis, and occurred at the mean 30.3 months (range: 1.26–226 months) after brachytherapy. In the whole cohort, younger age (p = 0.042), plaque type (p = 0.001) and ciliary body involvement (p < 0.0001) were independently associated with the RISN occurrence. In the case–control study, multivariable weighted proportional hazard analysis discovered the association of the following additional tumour‐ and treatment‐associated characteristics with RISN: posterior tumour margin anterior to equatorial region (p = 0.0003), extraocular tumour extension (p = <0.0001), scleral contact dose (p = <0.0001), conjunctival dehiscence after therapy (p = 0.0001), disinsertion of the superior rectus muscle (p = 0.001) and the glaucoma medication (p = 0.014).ConclusionsOur study confirms RISN as a rare complication, which might occur even years later after the brachytherapy for uveal melanoma. Alongside with scleral dose five other tumour and therapy related factors predict the risk of RISN after brachytherapy for uveal melanoma were established.
Severe congenital cutis laxa: Identification of novel homozygous LOX gene variants in two families
Authors: McKenzie Fiona , Mina Kym , Callewaert Bert , Beyens Aude , Dickinson Jan E. , Jevon Gareth , Papadimitriou John , Diness Birgitte Rode , Steensberg Jesper Norman , Ek Jakob , Baynam Gareth 
Published: April 2021

AbstractWe report three babies from two families with a severe lethal form of congenital cutis laxa. All three had redundant and doughy‐textured skin and two siblings from one family had facial dysmorphism. Echocardiograms showed thickened and poorly contractile hearts, arterial dilatation and tortuosity. Post‐mortem examination in two of the babies further revealed widespread ectasia and tortuosity of medium and large sized arteries, myocardial hypertrophy, rib and skull fractures. The presence of fractures initially suggested a diagnosis of osteogenesis imperfecta. Under light microscopy bony matrices were abnormal and arterial wall architecture was grossly abnormal showing fragmented elastic fibres. Molecular analysis of known cutis laxa genes did not yield any pathogenic defects. Whole exome sequencing of DNA following informed consent identified two separate homozygous variants in the LOX (Lysyl Oxidase) gene. LOX belongs to the 5‐lysyl oxidase gene family involved in initiation of cross‐linking of elastin and collagen. A mouse model of a different variant in this gene recapitulates the phenotype seen in the three babies. Our findings suggest that the LOX gene is a novel cause of severe congenital cutis laxa with arterial tortuosity, bone fragility and respiratory failure.
Single‐use device endoscopy for the diagnosis of acute bacterial rhinosinusitis in primary care: A pilot and feasibility study
Authors: Glinz Dominik , Georg Hansen Jens , Trutmann Caroline , Schaller Bernhard , Vogt Jürg , Diermayr Claus , Marti Andreas , Leitmeyer Katharina , Doerig Patrick , Zeller Andreas , Welge‐Luessen Lemcke Antje , Bucher Heiner C. 
Published: April 2021

AbstractObjectiveAntibiotics are largely overprescribed for acute rhinosinusitis in primary care, mainly due to the lack of diagnostic tests to confirm or rule out bacterial infection. The study objective was to assess the on‐site applicability and safety of the newly developed JGG endoscope® for the diagnosis of acute bacterial rhinosinusitis in primary care.DesignFive Swiss primary care centres and one university‐affiliated ENT unit participated in this single‐arm pilot study.ParticipantsAdults with acute suspected bacterial rhinosinusitis. The newly developed JGG endoscope®, which is attached to a pocket otoscope, was used to inspect after local anaesthesia the nasal cavity and middle meatus and to gain material for bacterial culture from paranasal sinuses draining ostium.Main outcome measuresApplicability and safety.ResultsThe visualisation of the middle meatus was successful in 16 of 21 patients (13 in both sides and three in one side), and unclear or unsuccessful in five patients. Sample collection from the middle meatus was successful in 10 patients (six on both and four on one side) and unclear or unsuccessful in the remaining patients. Only one culture‐confirmed bacterial rhinosinusitis and 11 PCR‐confirmed viral infections were identified from collected samples. After a 2‐week follow‐up, no serious adverse events were observed.ConclusionsThe on‐site use of the JGG endoscope® in daily primary care routine is feasible and safe and was well accepted by the trial physicians and patients (assessed with structured questionnaires). The JGG endoscope® may support general practitioners to differentiate between bacterial and viral rhinosinusitis.
CT‐guided microcoil localization for pulmonary nodules in the scapula‐shadowed area before Video‐Assisted Thoracic Surgery
Authors: Xu Yanyan , Ma Lingchuan , Lin Jie , Sun Hongliang , Huang Zhenguo , Zhang Zhenrong , Xiao Fei , Ma Qianli 
Published: April 2021

AbstractPurposeTo evaluate the feasibility and safety of CT‐guided microcoil localization for pulmonary nodules in the scapula‐shadowed area before video‐assisted thoracic surgery (VATS).Materials and MethodsForty‐seven patients (18 males, 19 females; mean age 57.5 years) with 48 pulmonary nodules covered by the scapulae were consecutively enrolled in this study. Successful targeting, localization, and VATS were defined as implantation of microcoil at the target site on CT image obtained immediately after the marking procedure, visualization of nodule location during VATS, and complete resection of the target nodule with adequate margin, respectively. Meanwhile, the procedure‐related complication rate was also recorded.ResultsThe rates of successful targeting and localization were 95.8% (46/48) and 89.6% (43/48), respectively. Of all nodules, 47 were successfully resected with VATS (30 wedge resections; 17 anatomic resections) and 1 nodule was converted to open thoracotomy for diffuse pleural adhesion, thus the successful VATS rate was 97.9% (47/48).With respect to procedure‐related complications, only minor complications (including localized pneumothorax and intrapulmonary hemorrhage) were developed and the rate of overall procedure‐related complications was 37.5% (18/48), including minor pneumothorax developed in 15 of 48 nodules (31.3%) and intrapulmonary hemorrhage in 6 of 48 nodules (12.5%).ConclusionsCT‐guided microcoil technique is a safe and effective localization method prior to VATS for the nodules in the scapula‐shadowed area.
Obesity is a risk factor for progression to kidney transplant waitlisting after liver transplantation
Authors: Locke Jayme E. , Shelton Brittany , Orandi Babak , Olthoff Kim , Pomfret Elizabeth , Forde Kimberly A. , Sawinski Deirdre , Gray Meagan , Ascher Nancy 
Published: April 2021

AbstractBackgroundNon‐alcoholic steatohepatitis has emerged as a leading cause of cirrhosis, and obesity‐associated comorbidities, including renal disease, have increased in prevalence. Obesity predisposes the kidney to hyperfiltration injury, potentially impairing acute kidney injury recovery. Identification of patients at risk for renal dysfunction is impeded by poor performance of renal function estimating equations among cirrhotics. To better understand obesity among cirrhotics and renal disease progression, we examined likelihood of kidney transplantation (KT) waitlisting after liver transplant alone (LTA) by obesity class.Methods68 607 LTA recipients were identified in SRTR (2005–2018). Fine and Gray competing risks models were used to analyze likelihood of KT waitlisting.Results27.4% of recipients were obese (BMI ≥ 30 kg/m2) and were 10% more likely to require KT waitlisting (aHR: 1.10, 95%CI: 1.01–1.20). Risk was highest among recipients with Classes II and III obesity (BMI: ≥35 kg/m2) (aHR: 1.37, 95%CI: 1.17–1.56). Moreover, recipients with Classes II and III obesity were 57% more likely to require KT waitlisting within one year post‐LTA (aHR: 1.57, 95%CI: 1.18–2.10) compared to non‐obese recipients.DiscussionThese findings suggest obesity was a risk factor for renal recovery failure and/or renal disease progression post‐LTA and may confound identification of renal dysfunction and/or prediction of renal recovery among cirrhotics.
Ecology of Oobius rudnevi, egg parasitoid of Cerambyx cerdo and Cerambyx welensii in oak forests
Authors: Torres‐Vila Luis M. , López‐Calvo Rafael , Sánchez‐González Álvaro , Mendiola‐Díaz F. Javier 
Published: April 2021

AbstractOobius rudnevi (Nowicki) (Hymenoptera: Encyrtidae) is a gregarious egg parasitoid of Cerambyx cerdo L. and Cerambyx welensii (Küster) (Coleoptera: Cerambycidae), two well‐known large oak‐living saproxylic beetles with different pest/legal status: whereas C. cerdo is a protected species, C. welensii is considered an emerging pest. Despite the potential interest of O. rudnevi as a native parasitoid, the knowledge of its biology remains very limited. We used sentinel eggs to assess the distribution of O. rudnevi in Extremadura (southwest Spain) and to explore its ecology, phenology, behavior, parasitism rates, and host preference. More than 13 500 sentinel eggs, housed in 1 030 wood disks, were field‐exposed during 2016–2018 in 147 oak stands over an array of oak forests. Oobius rudnevi was the only egg parasitoid detected, being widespread and relatively abundant over the studied area (90/147 stands, 61.2%) with adults flying in May–July. Parasitoids were detected in both host species, but net parasitism (PN) was significantly higher in C. cerdo (22.4%) than in C. welensii (9.5%). Net parasitism was affected by altitude (it was higher at 600–800 m) and tended to increase in colder aspects; PN was poorly related to host egg density (no. eggs per disk) and unrelated to host population size (no. adults per trap). Most parasitoids overwintered and emerged in the following spring (synchronously with their hosts) but some phenotypes/lineages did not undergo obligate diapause and were bivoltine. Bivoltine wasps were spatially widespread (27/90 stands, 30%), even if their actual prevalence was rather low (60/1641 parasitized eggs, 3.7%). We also found that O. rudnevi was slightly protogynous, the sex ratio was female‐biased, and the mean (± SEM) number of wasps emerging per parasitized egg was 9.3 ± 0.1 (range 1–29). We discuss the potential role of O. rudnevi as a biological control agent from an evolutionary perspective.
Effect of adult feeding on the δ15N signatures of different tissues for Popillia japonica
Authors: Henden Jacob , Guédot Christelle 
Published: April 2021

AbstractAs insects feed, stable isotopes from their diets are assimilated into their tissues. Stable isotopes provide a method to determine what insects are feeding on, and in some cases, where the insects have been feeding. One method for evaluating what adult holometabolous insects fed on as larvae, is to sample tissues from the integument of the adult. The integument should have isotopic signatures that reflect the diet of the larvae, and these inert tissues should be less influenced by adult feeding compared to other tissues. The objective of our research was to examine how isotopic signatures of nitrogen in various tissues of adult Popillia japonica (Newman) (Coleoptera: Scarabaeidae) beetles would be influenced by adults feeding on 15N‐enriched plant material. We collected adults from emergences cages at unenriched grasses and fed them for 0, 2, 5, or 10 days with grape plants fertilized with isotopically enriched or unenriched potassium nitrate. The δ15N signature of elytra and soft tissues both increased over time when fed enriched plant material. The δ15N signatures of soft tissues were higher than that of the elytra over time. Adult beetles fed highly enriched plant material displayed increased δ15N signatures over time of tissues generally considered metabolically inactive, which suggests that adult feeding does contribute to the isotopic signatures of elytra tissue. The difference between the δ15N signatures of soft tissues and elytra demonstrates a lower turnover rate in the elytra and highlights the fact that diet does contribute to the signature of elytra.