bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of treatment response in chronic spontaneous urticaria
Authors: Fok Jie Shen , Kolkhir Pavel , Church Martin K. , Maurer Marcus 
Published: February 2021

AbstractThe current therapeutic algorithm for chronic spontaneous urticaria (CSU), endorsed by the international guideline, entails treatment escalation from second‐generation H1‐antihistamines (sgAHs) to omalizumab and cyclosporine until complete response is achieved. Recently, several predictors of response to these treatment options have been described. Here, we discuss the most promising predictors of response and nonresponse to these treatments in CSU. A systematic search was performed by two independent researchers using the MEDLINE/PubMed database with specific keywords and 73 studies included in the review. Levels of evidence were categorized as strong (robust predictors), weak (emerging predictors) or no association, based on the outcome and number of studies available. High disease activity, high levels of C‐reactive protein and D‐dimer are robust predictors for a poor or no response to sgAHs. Poor or no response to omalizumab is robustly predicted by low serum levels of total IgE. A good response to cyclosporine is robustly predicted by a positive basophil histamine release assay, whereas low total IgE is an emerging predictor. The response to treatment with sgAHs, omalizumab and cyclosporine can be predicted by the use of markers that are readily available in routine clinical practice. Further studies are needed to confirm these predictors.
IL‐1β promotes immunoregulatory responses in human blood basophils
Authors: Iype Joseena , Odermatt Andrea , Bachmann Sofia , Coeudevez Mazarine , Fux Michaela 
Published: February 2021

AbstractHuman basophils are essential effector cells of chronic allergic inflammation. IL‐1 family cytokines such as interleukin (IL)‐33 and IL‐1β are elevated in serum and bronchoalveolar lavage fluid of allergic asthmatics. IL‐33 is known to be a critical regulator of basophil's T2 immune responses. However, the effect of IL‐1β on the function of basophils has not been well investigated. Here, we elucidate whether IL‐1β regulates the function of human basophils and compared the effects of IL‐1β and IL‐33 on basophils of healthy and allergic subjects. We found that IL‐1β activates the p38 MAPK signaling pathway and promotes IL‐8 release in basophils of healthy donors, while FcεRI‐mediated LCT4and histamine secretion is not affected. Strikingly, in the presence of IL‐3, IL‐1β shows more potency than IL‐33, as evidenced by the enhanced p38 phosphorylation and NF‐κB activation, as well as the release of both IL‐13 and IL‐8. We found that the enhanced basophil responsiveness is achieved through IL‐3‐induced IL‐1RI surface expression. Importantly, basophils of allergic donors release significantly higher amounts of IL‐8 compared to those from healthy donors upon IL‐33 and IL‐1β stimulation. Consistently, we detected increased IL‐1RI and decreased IL‐3 receptor alpha‐chain (CD123) and CCR3 expression on basophils of allergic subjects compared to healthy controls, suggesting an in vivo IL‐3 priming in allergic donors. In summary, our results suggest enhanced sensitivity of basophils toward IL‐33 and IL‐1β in allergic subjects compared to those from healthy controls.
Regulatory B cells, A to Z
Authors: Jansen Kirstin , Cevhertas Lacin , Ma Siyuan , Satitsuksanoa Pattraporn , Akdis Mübeccel , van de Veen Willem 
Published: February 2021

AbstractB cells play a central role in the immune system through the production of antibodies. During the past two decades, it has become increasingly clear that B cells also have the capacity to regulate immune responses through mechanisms that extend beyond antibody production. Several types of human and murine regulatory B cells have been reported that suppress inflammatory responses in autoimmune disease, allergy, infection, transplantation, and cancer. Key suppressive molecules associated with regulatory B‐cell function include the cytokines IL‐10, IL‐35, and TGF‐β as well as cell membrane‐bound molecules such as programmed death‐ligand 1, CD39, CD73, and aryl hydrocarbon receptor. Regulatory B cells can be induced by a range of different stimuli, including microbial products such as TLR4 or TLR9 ligands, inflammatory cytokines such as IL‐6, IL‐1β, and IFN‐α, as well as CD40 ligation. This review provides an overview of our current knowledge on regulatory B cells. We discuss different types of regulatory B cells, the mechanisms through which they exert their regulatory functions, factors that lead to induction of regulatory B cells and their role in the alteration of inflammatory responses in different diseases.
Scaffold‐free tissue‐engineered arterial grafts derived from human skeletal myoblasts
Authors: Saito Junichi , Yokoyama Utako , Nakamura Takashi , Kanaya Tomomitsu , Ueno Takayoshi , Naito Yuji , Takayama Toshio , Kaneko Makoto , Miyagawa Shigeru , Sawa Yoshiki , Ishikawa Yoshihiro 
Published: February 2021

AbstractTissue‐engineered vascular grafts (TEVGs) are in urgent demand for both adult and pediatric patients. Although several approaches have utilized vascular smooth muscle cells (SMCs) and endothelial cells as cell sources for TEVGs, these cell sources have a limited proliferative capacity that results in an inability to reconstitute neotissues. Skeletal myoblasts are attractive cell sources as they possess high proliferative capacity, and they are already being tested in clinical trials for patients with ischemic cardiomyopathy. Our previous study demonstrated that periodic hydrostatic pressurization (PHP) promoted fibronectin fibrillogenesis in vascular SMCs, and that PHP‐induced extracellular matrix (ECM) arrangements enabled the fabrication of implantable arterial grafts derived from SMCs without using a scaffold material. We assessed the molecular response of human skeletal myoblasts to PHP exposure, and aimed to fabricate arterial grafts from the myoblasts by exposure to PHP. To examine the PHP‐response genes, human skeletal myoblasts were subjected to bulk RNA‐sequencing after PHP exposure. Gene‐set enrichment analysis revealed significant positive correlations between PHP exposure and vascular development‐related genes. Real‐time polymerase chain reaction (RT‐PCR) demonstrated that PHP significantly upregulated collagen and elastic fiber formation‐related gene expression, such as fibronectin, lysyl oxidase, collagen type I α1, collagen type IV α1, and tropoelastin. Based on these findings showing the potential role of PHP in vessel formation, we fabricated arterial grafts by repeated cell seeding and exposure to PHP every 24 hours. The resultant 15‐layered myoblast grafts had high collagen content, which provided a tensile rupture strength of 899 ± 104 mm Hg. Human skeletal myoblast grafts were implanted as patch grafts in the aorta of immunosuppressed rats and found to be endothelialized and completely patent until the endpoint of 60 postoperative days. Implanted human myoblasts were gradually replaced by host‐derived cells, which successfully formed vascular neotissues with layered elastic fibers. These findings suggest that human skeletal myoblasts have the potential to be a feasible cell source for scaffold‐free implantable arterial grafts under PHP culture conditions.
Comparison of different methods of retinal imaging for the screening of diabetic retinopathy: a systematic review
Authors: Kárason Kolbeinn Tumi , Vo Diana , Grauslund Jakob , Rasmussen Malin Lundberg 
Published: February 2021

AbstractBackgroundScreening for diabetic retinopathy (DR) is recommended to detect sight‐threatening complications prior to visual loss. Early Treatment Diabetic Retinopathy Study (ETDRS) seven standard field (7SF) retinal imaging has traditionally been regarded the gold standard for DR classification, but other methods are often preferred clinically. The purpose of this systematic review was to determine whether 7SF is the most optimal screening method for DR grading, or if similar results can be achieved by other methods using a smaller field of view (<7SF) or ultra‐wide field (UWF) imaging.MethodsBased on Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guidelines, two independent reviewers initially identified 7167 publications in PubMed, Cochrane and Embase databases. Of these, 16 publications were included based on predefined inclusion criteria.Results7SF was used as reference standard in 12 studies (compared with < 7SF in five studies and UWF in seven studies), and four studies compared other reference standards. Compared to 7SF, studies using < 7SF and UWF images both reported of similar agreement. A lower rate of ungradable images was reported for mydriatic and non‐mydriatic UWF as compared to non‐mydriatic < 7SF modalities.ConclusionRetinal imaging of <7SF and UWF both provide acceptable performance compared to 7SF. Given the time‐consuming nature of the latter, these methods could be reasonable options in DR screening, even though a high number of ungradable images in non‐mydriatic < 7SF may pose a clinical challenge.
Post‐dural puncture headache—a single‐centre analysis in paediatric patients with and without SMA
Authors: Schorling David C. , Pechmann Astrid , Eckenweiler Matthias , Müller Cornelia K. , Langer Thorsten , Kirschner Janbernd 
Published: February 2021

AbstractAimTo gather epidemiologic data on post‐dural puncture headache (PDPH) after diagnostic or therapeutic lumbar puncture (LP) in children and adolescents with SMA as well as in a cohort of paediatric patients without SMA.MethodsWe performed a retrospective, single‐centre analysis via chart review and questionnaire. Patients were identified using the German procedure classification. Respective charts and SMArtCARE documentation forms (SMA patients) were reviewed concerning documentation of headaches fulfilling criteria of the IHS‐classification for PDPH of 2004. Non‐SMA patients received additional questionnaires.ResultsWe identified a total of 218 LPs in 95 patients. Of those 141 were performed in 22 patients with known SMA (mean age SMA patients 9.2 years; non‐SMA patients 11.4 years). Following chart review, IHS criteria for PDPH were fulfilled in 6.9% of all procedures (3.5% in SMA patients; 13.0% in non‐SMA patients; p = 0.008). Data from questionnaires of non‐SMA patients confirmed this result (position dependent headache within 72 h after intervention in 13.0% of procedures).ConclusionThe prevalence of PDPH after therapeutic LPs in our cohort of SMA patients was significantly lower than after LPs in the general paediatric cohort. Data of this retrospective analysis show a similar overall prevalence of PDPH in paediatric patients as reported in bigger adult cohorts.
Relationship among genetic polymorphism of SLCO1B1, rifampicin exposure and clinical outcomes in patients with active pulmonary tuberculosis
Authors: Kim Eun Sun , Kwon Byoung Soo , Park Jong Sun , Chung Jae‐Yong , Seo Soo Hyun , Park Kyoung Un , Song Junghan , Yoon Seonghae , Lee Jae Ho 
Published: February 2021

AimsRifampicin is a key drug for the treatment of tuberculosis (TB). Little is known for the relationship between the rifampicin pharmacokinetics and genetic polymorphisms in the Asian population. We aimed to investigate relationship between genetic polymorphism of SLCO1B1 and rifampicin exposure and its impact on clinical outcomes in Korean patients with active pulmonary TB.MethodsFrom February 2016 to December 2019, patients with active pulmonary TB who were taking rifampicin for >1 week were prospectively enrolled. Serial or 1‐time blood sampling was conducted to determine rifampicin concentrations. The genotype of 4 single nucleotide polymorphisms of SLCO1B1 was determined. To estimate the drug clearance and exposure, population pharmacokinetics analysis was conducted. Clinical outcomes such as time to acid‐fast bacteria culture conversion, chest radiograph score changes from baseline, and all‐cause mortality were also evaluated. The exposure among different SLCO1B1 genotype was compared and relationship between drug exposure and clinical outcomes were explored.ResultsA total of 105 patients (70 males and 35 females) were included in the final analysis. The mean age of patients was 55.4 years. The mean drug clearance and exposure were 13.6 L/h and 57.9 mg h/L, respectively. The genetic polymorphisms of SLCO1B1 were not related to rifampicin clearance or exposure. As the rifampicin exposure increased, the chest radiographs improved significantly, but the duration of acid‐fast bacteria culture conversion was not related to the drug exposure.ConclusionSLCO1B1 gene polymorphisms did not influence rifampicin concentrations and clinical outcomes in Korean patients with active pulmonary TB.
Acylated ghrelin protects against doxorubicin‐induced nephropathy by activating silent information regulator 1
Authors: Shati Ali A. , El‐Kott Attalla F. 
Published: February 2021

AbstractThis study investigated the nephroprotective role of acylated ghrelin (AG) against DOX‐induced nephropathy and examined whether the protection involves silent information regulator 1 (SIRT1). Rats were divided into control, control + AG, DOX, DOX + AG, DOX + AG + [D‐Lys3]‐GHRP‐6 (a ghrelin receptor antagonist), and DOX + AG + EX‐527 (a sirt1 inhibitor). DOX was given over the first 2 weeks. AG (10 ng/kg) and both inhibitors were given as 3 doses/wk for 5 weeks. AG improved the structure and the function of the kidneys; down‐regulated the renal expression of TGF‐β1, collagen 1A1 and α‐SMA; and inhibited the renal collagen deposition in the kidneys of DOX‐treated rats. Concomitantly, it reduced the renal levels of ROS, MDA, TNF‐α, and IL‐6 and protein levels of cytochrome‐c, TGF‐β1, Smad3 and α‐SMA in these rats. In both the control and DOX‐treated rats, AG significantly increased the renal levels of SOD and GSH, decreased the expression of cleaved caspase‐3 and Bax, increased the total levels and the nuclear activity of SIRT1 and reduced the deacetylation of p53, NF‐κB and FOXO‐31. All the effects were abolished by the concurrent administration of EX‐527 and [D‐Lys3]‐GHRP‐6. In conclusion, AG prevents DOX‐induced nephropathy in SIRT1 and GSHRa1‐dependent mechanism.
A survey of health care practitioners’ attitudes toward shared decision‐making for choice of next birth after cesarean
Authors: Munro Sarah , Wilcox Elizabeth S. , Lambert Leah K. , Norena Monica , Kaufman Sarah , Encinger Jana , Kendall Tamil , Thompson Rachel 
Published: February 2021

AbstractBackgroundPatients with a history of cesarean may benefit from shared decision‐making (SDM) interventions, such as patient decision aids, that provide individualized clinical information and help to clarify personal preferences. We sought to understand the factors that influence how care practitioners support choices for mode of birth and what individual and health system factors influence uptake of SDM in routine care.MethodsWe conducted a cross‐sectional survey of health care practitioners in British Columbia, Canada (2016‐2017). Participants included family physicians, midwives, obstetricians, and registered nurses. We conducted descriptive and inferential analyses of quantitative data and subjected the open‐ended survey responses to thematic analysis.ResultsAnalysis of survey responses (n = 307) suggested there was no significant association between the size of the participant hospital and their medico‐legal concerns about mode of birth. Environmental factors that may influence the use of SDM included the length of time it takes to initiate an emergency cesarean and the timing of when the SDM intervention is introduced to the patient. No participants reported protocols prohibiting VBAC at their hospital. Participants preferred an SDM approach where the pregnant person is involved in making the final decision for mode of birth.ConclusionsAlthough maternity care practitioners express attitudes and behaviors that may support SDM for mode of birth after cesarean, implementing SDM using a patient decision aid alone may be challenging because of environmental factors. Our study demonstrates how survey data can aid in identifying how, when, where, for whom, and why an SDM intervention could be implemented.
Principles of shortening in salt basins containing isolated minibasins
Authors: Duffy Oliver B. , Dooley Tim P. , Hudec Michael R. , Fernandez Naiara , Jackson Christopher A.‐L. , Soto Juan I. 
Published: February 2021

AbstractShortening styles in salt‐influenced basins can vary markedly, with the volume and distribution of salt prior to shortening being a key control. Here, we use a suite of physical models to examine styles of thin‐skinned regional shortening in settings where the preshortening structure comprised minibasins surrounded by salt (‘isolated‐minibasin’ provinces). Our models show that the high volume of mechanically weak salt localizes lateral regional shortening, with shortening inducing salt flow towards the foreland that subsequently contributes to three key processes – translation, tilting and rotation of minibasins. First, we demonstrate that the flowing salt pushes against minibasins, propelling them in the regional shortening direction. Minibasin translation is enhanced by fast‐flowing salt streams and impeded by basal friction due to welding and base‐salt buttresses. Second, we show how minibasin tilt directions and magnitudes vary spatially and temporally during regional shortening. Minibasins tilt away from zones of pressurized salt, the locations of which may shift due to changes in salt flow regimes. Tilt directions may also change as minibasins pivot on primary welds, or due to forces associated with minibasin collision. Third, minibasins can rotate around sub‐vertical axes during regional shortening. We speculate that this rotation is caused by a combination of: (a) traction imparted on the minibasin boundary by differential horizontal flow of adjacent salt; and (b) pivoting on primary and secondary welds. We synthesize our results in a series of 3‐D conceptual models, before we compare and contrast regional shortening styles and processes in salt‐influenced basins with different preshortening salt configurations. Our findings contribute to the understanding of the geometry and kinematics of shortened salt basins, as well as a deeper understanding of the tectono‐stratigraphic evolution of minibasins.
A farewell to arms and legs: a review of limb reduction in squamates
Authors: Camaiti Marco , Evans Alistair R. , Hipsley Christy A. , Chapple David G. 
Published: February 2021

ABSTRACTElongated snake‐like bodies associated with limb reduction have evolved multiple times throughout vertebrate history. Limb‐reduced squamates (lizards and snakes) account for the vast majority of these morphological transformations, and thus have great potential for revealing macroevolutionary transitions and modes of body‐shape transformation. Here we present a comprehensive review on limb reduction, in which we examine and discuss research on these dramatic morphological transitions. Historically, there have been several approaches to the study of squamate limb reduction: (i) definitions of general anatomical principles of snake‐like body shapes, expressed as varying relationships between body parts and morphometric measurements; (ii) framing of limb reduction from an evolutionary perspective using morphological comparisons; (iii) defining developmental mechanisms involved in the ontogeny of limb‐reduced forms, and their genetic basis; (iv) reconstructions of the evolutionary history of limb‐reduced lineages using phylogenetic comparative methods; (v) studies of functional and biomechanical aspects of limb‐reduced body shapes; and (vi) studies of ecological and biogeographical correlates of limb reduction. For each of these approaches, we highlight their importance in advancing our understanding, as well as their weaknesses and limitations. Lastly, we provide suggestions to stimulate further studies, in which we underscore the necessity of widening the scope of analyses, and of bringing together different perspectives in order to understand better these morphological transitions and their evolution. In particular, we emphasise the importance of investigating and comparing the internal morphology of limb‐reduced lizards in contrast to external morphology, which will be the first step in gaining a deeper insight into body‐shape variation.
Characteristics of B lymphocyte infiltration in HPV+ head and neck squamous cell carcinoma
Authors: Zhang Siwei , Wang Bozhi , Ma Fen , Tong Fangjia , Yan Bingqing , Liu Tianyang , Xie Huanhuan , Song Lianhao , Yu Siyang , Wei Lanlan 
Published: February 2021

AbstractHuman papillomavirus (HPV) is an important etiological factor of head and neck squamous cell carcinoma (HNSCC). HPV+ HNSCC patients usually have a better prognosis, which probably results from the higher infiltration of B lymphocytes. This study was purposed to detect the infiltration of B lymphocyte subsets and the correlation between B lymphocyte subsets and the prognosis in HPV‐related HNSCC. In this study, 124 HPV+ and 513 HPV− HNSCC samples were obtained from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database for transcriptomic analysis. Infiltration of B lymphocytes subsets was detected with 7 HPV+ HNSCC and 13 HPV− HNSCC tissues through immunohistochemistry and immunofluorescence. One HPV− HNSCC sample was detected with single‐cell sequencing for chemokine analysis. In the results, the infiltration of plasma cells (CD19+CD38+) and memory B cells (MS4A1+CD27+) was higher in HPV+ HNSCC samples. High infiltration of plasma cells and memory B cells was related to a better prognosis. High density of B lymphocytes was positively correlated with high CXCL13 production mainly from CD4+ T lymphocytes in HNSCC. These results indicated that a high density of plasma cells and memory B cells could predict excellent prognosis. CD4+ T lymphocytes might affect B lymphocytes and their subsets through the CXCL13/CXCR5 axis in HNSCC.
Growth‐differentiation‐factor 15 levels in obese and healthy pregnancies: Relation to insulin resistance and insulin secretory function
Authors: Andersson‐Hall Ulrika , Joelsson Louise , Svedin Pernilla , Mallard Carina , Holmäng Agneta 
Published: February 2021

AbstractObjective/AimGrowth‐differentiation‐factor 15 (GDF15) has been suggested to improve or protect beta cell function. During pregnancy, beta cell numbers and function increase to overcome the natural rise in insulin resistance during gestation. In this study, we longitudinally measured serum GDF15 levels during and after pregnancy in women of normal weight (NW) and in women with obesity (OB) and explored associations between GDF15 and changes in beta cell function by homeostatic model assessment (HOMA).MethodsThe cohort participants were 38 NW (BMI 22.3 ± 1.7) and 35 OB (BMI 35.8 ± 4.2). Blood was sampled and body composition measured at each trimester (T1, T2, and T3) and at 6, 12 and 18 months postpartum. Fasting glucose, insulin and GDF15 were measured, and HOMA for insulin resistance (HOMA‐IR) and beta cell function (HOMA‐B) determined.ResultsGDF15 levels increased significantly each trimester and were ~200‐fold higher at T3 than in the nonpregnant postpartum state. GDF15 was higher in NW than OB during pregnancy, but was reversed after pregnancy with a significant interaction effect. GDF15 correlated inversely with BMI and fat‐free mass at T3. Low GDF15 was associated with lower incidence of nausea and with carrying a male foetus. The pregnancy induced increase in GDF15 associated with increased HOMA‐B in OB and with reduced fasting glucose in all women.ConclusionLarge gestational upregulation of GDF15 levels may help increase insulin secretory function to overcome pregnancy‐induced insulin resistance.