bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances and highlights in biomarkers of allergic diseases
Authors: Ogulur Ismail , Pat Yagiz , Ardicli Ozge , Barletta Elena , Cevhertas Lacin , Fernandez‐Santamaria Ruben , Huang Mengting , Bel Imam Manal , Koch Jana , Ma Siyuan , Maurer Debbie J. , Mitamura Yasutaka , Peng Yaqi , Radzikowska Urszula , Rinaldi Arturo O. , Rodriguez‐Coira Juan , Satitsuksanoa Pattraporn , Schneider Stephan R. , Wallimann Alexandra , Zhakparov Damir , Ziadlou Reihane , Brüggen Marie‐Charlotte , van de Veen Willem , Sokolowska Milena , Baerenfaller Katja , Zhang Luo , Akdis Mubeccel , Akdis Cezmi A. 
Published: September 2021

AbstractDuring the past years, there has been a global outbreak of allergic diseases, presenting a considerable medical and socioeconomical burden. A large fraction of allergic diseases is characterized by a type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, eosinophils, mast cells, and M2 macrophages. Biomarkers are valuable parameters for precision medicine as they provide information on the disease endotypes, clusters, precision diagnoses, identification of therapeutic targets, and monitoring of treatment efficacies. The availability of powerful omics technologies, together with integrated data analysis and network‐based approaches can help the identification of clinically useful biomarkers. These biomarkers need to be accurately quantified using robust and reproducible methods, such as reliable and point‐of‐care systems. Ideally, samples should be collected using quick, cost‐efficient and noninvasive methods. In recent years, a plethora of research has been directed toward finding novel biomarkers of allergic diseases. Promising biomarkers of type 2 allergic diseases include sputum eosinophils, serum periostin and exhaled nitric oxide. Several other biomarkers, such as pro‐inflammatory mediators, miRNAs, eicosanoid molecules, epithelial barrier integrity, and microbiota changes are useful for diagnosis and monitoring of allergic diseases and can be quantified in serum, body fluids and exhaled air. Herein, we review recent studies on biomarkers for the diagnosis and treatment of asthma, chronic urticaria, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, food allergies, anaphylaxis, drug hypersensitivity and allergen immunotherapy. In addition, we discuss COVID‐19 and allergic diseases within the perspective of biomarkers and recommendations on the management of allergic and asthmatic patients during the COVID‐19 pandemic.
An active approach of pressure waveform matching for stress‐based testing of arteries
Authors: Agrafiotis Emmanouil , Geith Markus A. , Golkani Mohammad A. , Hergesell Vera , Sommer Gerhard , Spiliopoulos Sotirios , Holzapfel Gerhard A. 
Published: September 2021

AbstractBackgroundArterial compliance assists the cardiovascular system with three key roles: (i) storing up to 50% of the stroke volume; (ii) ensuring blood flow during diastole; (iii) dampening pressure oscillations through arterial distension. In mock circulation loops (MCLs), arterial compliance was simulated either with membrane, spring, or Windkessel chambers. Although they have been shown to be suitable for cardiac device testing, their passive behavior can limit stress‐based testing of arteries. Here we present an active compliance chamber with a feedback control of variable compliance as part of an MCL designed for biomechanical evaluation of arteries under physiological waveforms.Materials and MethodsThe chamber encloses a piston that changes the volume via a cascaded controller when there is a difference between the real‐time pressure and the physiological reference pressure with the aim to equilibrate both pressures.ResultsThe experimental results showed repeatable physiological waveforms of aortic pressure in health (80–120 mm Hg), systemic hypertension (90–153 mm Hg), and heart failure reduced ejection fraction (78–108 mm Hg). Statistical validation (n = 20) of the function of the chamber is presented against compared raw data.ConclusionWe demonstrate that the active compliance chamber can track the actual pressure of the MCL and balance it in real time (every millisecond) with the reference values in order to shape the given pressure waveform. The active compliance chamber is an advanced tool for MCL applications for biomechanical examination of stented arteries and for preclinical evaluation of vascular implants.
Schlemm's canal: the outflow ‘vessel’
Authors: Lewczuk Katarzyna , Jabłońska Joanna , Konopińska Joanna , Mariak Zofia , Rękas Marek 
Published: September 2021

AbstractIn a healthy eye, the aqueous humour (AH) flows via the ciliary body and trabecular meshwork into the collector channels, which carry it to the episcleral veins. In glaucoma, a heterogeneous group of eye disorders affecting approximately 60 million individuals worldwide, the juxtacanalicular meshwork offers greater resistance to the outflow of the AH, leading to an increase in outflow resistance that gradually results in elevated intraocular pressure (IOP). The present review comprehensively covers the morphology of Schlemm’s canal (SC) and AH pathways. The path of the AH from the anterior chamber through the trabeculum into suprascleral and conjunctival veins via collector channels is described, and the role of SC in the development of glaucoma and outflow resistance is discussed. Finally, channelography is presented as a precise method of assessing the conventional drainage pathway and facilitating localization of an uncollapsed collector and aqueous veins. Attention is also given to the relationship between aqueous and episcleral veins and heartbeat. Possible directions of future research are proposed.
Glucagon‐like peptide‐1 (GLP‐1) signalling in the brain: From neural circuits and metabolism to therapeutics
Authors: Kabahizi Anita , Wallace Briana , Lieu Linh , Chau Dominic , Dong Yanbin , Hwang Eun‐Sang , Williams Kevin W. 
Published: September 2021

Glucagon‐like‐peptide‐1 (GLP‐1) derived from gut enteroendocrine cells and a discrete population of neurons in the caudal medulla acts through humoral and neural pathways to regulate satiety, gastric motility and pancreatic endocrine function. These physiological attributes contribute to GLP‐1 having a potent therapeutic action in glycaemic regulation and chronic weight management. In this review, we provide an overview of the neural circuits targeted by endogenous versus exogenous GLP‐1 and related drugs. We also highlight candidate subpopulations of neurons and cellular mechanisms responsible for the acute and chronic effects of GLP‐1 and GLP‐1 receptor agonists on energy balance and glucose metabolism. Finally, we present potential future directions to translate these findings towards the development of effective therapies for treatment of metabolic disease.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
The role of glia in the physiology and pharmacology of glucagon‐like peptide‐1: implications for obesity, diabetes, neurodegeneration and glaucoma
Authors: Cui Qi N. , Stein Lauren M. , Fortin Samantha M. , Hayes Matthew R. 
Published: September 2021

The medical applications of glucagon‐like peptide‐1 receptor (GLP‐1R) agonists is evergrowing in scope, highlighting the urgent need for a comprehensive understanding of the mechanisms through which GLP‐1R activation impacts physiology and behaviour. A new area of research aims to elucidate the role GLP‐1R signalling in glia, which play a role in regulating energy balance, glycemic control, neuroinflammation and oxidative stress. Once controversial, existing evidence now suggests that subsets of glia (e.g. microglia, tanycytes and astrocytes) and infiltrating macrophages express GLP‐1Rs. In this review, we discuss the implications of these findings, with particular focus on the effectiveness of both clinically available and novel GLP‐1R agonists for treating metabolic and neurodegenerative diseases, enhancing cognition and combating substance abuse.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
The flip side of reactive oxygen species in the tropical disease‐Amoebiasis
Authors: Desure Sakshi , Mallika Arya , Roy Mrinalini , Jyoti Anupam , Kaushik Sanket , Srivastava Vijay Kumar 
Published: September 2021

AbstractEntamoeba histolytica is the conductive agent of amoebiasis. Upon the parasite's infection, macrophages and neutrophils are activated by interferon γ, IL‐13 and tumour necrosis factor. These immune cells then carry out the amoebicidal activity by releasing nitric oxide synthase and reactive oxygen species (ROS). This review talks about the protective and destructive role of ROS in Eh. E. histolytica has defence strategies against oxidative stress which is a result of excess ROS production. They possess antioxidants for their defence such as L‐Cysteine, flavodiiron proteins, peroxiredoxin and trichostatin A, which contribute to the parasite’s virulence. The ROS are harmful to the host cells as excess ROS production stimulates cell death by mechanisms like apoptosis and necroptosis. NADPH oxidase (NOX) is a key source of ROS in mammalian cells and causes apoptosis of host cells via the protein kinase transduction pathway. This review provides insights into why NOX inhibitors that could be a potent antiparasitic drug, is not effective for in vivo purposes. This paper also gives an insight into a solution that could be a potent source in generating new treatment and vaccines for amoebiasis by targeting parasite development.
Chromones: Privileged scaffold in anticancer drug discovery
Authors: Patil Vaishali M. , Masand Neeraj , Verma Saroj , Masand Vijay 
Published: September 2021

AbstractIn the design and discovery of anticancer drugs, various natural heterocyclic scaffolds have attracted considerable interest as privileged structures. For rational drug design, some of the natural scaffolds such as chromones have exhibited wide acceptability due to their drug‐like properties. Among the approved anticancer drugs, the scaffolds with high selectivity for a small group of closely related targets are of importance. In the development of selective anticancer agents, the natural, as well as synthetic, can generate highly selective compounds toward cancer targets. The present manuscript includes more particularly the development of cancer inhibitors incorporating the chromone scaffold, with a strong emphasis on their molecular interactions in the anticancer mechanism. It also includes the structure‐activity relationship studies and related examples of lead optimization.
Bezafibrate induces hypothyroidism in a patient with resistance to thyroid hormone β due to a G347R variant
Authors: Yamauchi Ichiro , Yamashita Takafumi , Sugawa Taku , Tagami Tetsuya , Hanaoka Ikuko , Usui Takeshi , Hirota Keisho , Hakata Takuro , Ueda Yohei , Fujii Toshihito , Sakane Yoriko , Yasoda Akihiro , Inagaki Nobuya 
Published: September 2021

AbstractObjectiveA unique clinical course was observed in a patient with resistance to thyroid hormone β (RTHβ) caused by a variant of the THRB gene leading to the replacement of glycine with arginine in codon 347 (p.G347R). He presented with the syndrome of inappropriate secretion of thyrotropin (TSH) (free T4 [fT4]: 32.43 pmol/L, TSH: 4.67 mIU/L), but slowly developed progressive hypothyroidism (fT4: 8.37 pmol/L, TSH: 100.90 mIU/L) that resolved after suspending bezafibrate (BZ) treatment (fT4: 32.18 pmol/L, TSH: 7.14 mIU/L). This study clinically and experimentally evaluated this interesting phenomenon.MethodsA retrospective cohort analysis of non‐RTHβ patients was performed at Kyoto University Hospital. Data before BZ treatment were compared to the first data after treatment. Using reporter assays of iodothyronine deiodinases (DIO1, DIO2, DIO3) in HEK293T cells, we performed functional analyses of mutant thyroid hormone receptor β with p.G347R (G347R TRβ). Mice with G347R TRβ were generated by hydrodynamic gene delivery.ResultsIn non‐RTHβ patients (n = 7), BZ treatment did not change serum free T3 and TSH but significantly increased fT4 (p = .008). BZ administration increased DIO3 reporter activity in the context of G347R TRβ, whereas did not change DIO1 and DIO2 reporter activity. In the livers of mice with G347R TRβ, BZ administration increased reverse T3 content, which corresponded to an increase in Dio3 messenger RNA.ConclusionsWhile hypothyroidism associated with BZ treatment did not occur in non‐RTHβ patients, it was observed in a patient with RTHβ due to the p.G347R variant. Liver DIO3 upregulation might involve this hypothyroidism.
Opioid agonist treatment and patient outcomes during the COVID‐19 pandemic in south east Sydney, Australia
Authors: Lintzeris Nicholas , Deacon Rachel M. , Hayes Victoria , Cowan Tracy , Mills Llewellyn , Parvaresh Laila , Harvey Dodds Lucy , Jansen Louisa , Dojcinovic Raelene , Leung Man Cho , Demirkol Apo , Finch Therese , Mammen Kristie 
Published: September 2021

AbstractIntroductionIn early 2020, many services modified their delivery of opioid treatment in response to the COVID‐19 pandemic, to limit viral spread and maintain treatment continuity. We describe the changes to treatment and preliminary analysis of the association with patients' substance use and well‐being.MethodsA pre‐post comparison of treatment conditions and patient self‐reported outcomes using data extracted from electronic medical records in the 5 months before (December 2019–April 2020) and after (May 2020–September 2020) changes were implemented in three public treatment services in South Eastern Sydney Local Health District.ResultsData are available for 429/460 (93%) patients. Few (21, 5%) dropped out of treatment. In the ‘post’ period there was significantly more use of depot buprenorphine (12–24%), access to any take‐away doses (TAD; 24–69%), access to ≥6 TAD per week (7–31%), pharmacy dosing (24–52%) and telehealth services. There were significant reductions in average opioid and benzodiazepine use, increases in cannabis use, with limited group changes in social conditions, or quality of life, psychological and physical health. At an individual level, 22% of patients reported increases in their use of either alcohol, opioids, benzodiazepines or stimulants of ≥4 days in the past 4 weeks. Regression analysis indicates increases in substance use were associated with higher levels of supervised dosing.Discussion and ConclusionsThese preliminary findings suggest that the modified model of care continued to provide safe and effective treatment, during the pandemic. Notably, there was no association between more TAD and significant increases in substance use. Limitations are discussed and further evaluation is needed.
A small Rho GTPase OsRacB is required for pollen germination in rice
Authors: Xu Yangfan , Cai Wenguo , Chen Xiaofei , Chen Mingjiao , Liang Wanqi 
Published: September 2021

AbstractPlant Rho small GTPases (Rop/Rac) are versatile molecular switches regulating many plant developmental processes. Particularly, their important functions in regulating pollen development have been demonstrated in Arabidopsis. A group of conserved Rop/Rac activators RopGEFs were recently reported to regulate rice (Oryza sativa) pollen tube germination, indicating that rice and Arabidopsis may have a conserved Rop/Rac mediated signaling pathway in regulating pollen tube growth. However, the Rop/Rac activated by the rice pollen specific RopGEFs remains to be identified. Here we demonstrated a Rop/Rac gene, OsRacB, co‐expressed with the mature pollen expressed OsRopGEF2/3/6/8. The knockout mutants were normal in anther and pollen development but defective in the pollen grain germination, suggesting a specific and non‐redundant role of OsRacB in the mature pollen. We further demonstrated that OsRacB is directly activated by the pollen specific expressing OsRopGEFs in vitro. Together with the previous study, we establish a RopGEF‐Rop/Rac regulon which plays essential roles in rice pollen grain germination. Our data encourage further identification of the upstream and downstream players of RopGEF‐Rop/Rac signaling in pollen germination and have agricultural implications for breeding robust seed yielding cultivars.
Population stratification in type 2 diabetes mellitus: A systematic review
Authors: Hodgson Sam , Cheema Sukhmani , Rana Zareena , Olaniyan Doyinsola , O’Leary Ellen , Price Hermione , Dambha‐Miller Hajira 
Published: September 2021

AbstractAimsThere is increasing interest in using stratification in type 2 diabetes to target resources, individualise care and improve outcomes. We aim to systematically review and collate literature that has utilised population stratification methods in the study of adults with type 2 diabetes; and to describe and compare stratification methodologies, population characteristics, variables used to stratify and outcome variables.MethodsThe MEDLINE, EMBASE, CINAHL and Cochrane databases were searched from inception to July 2020. Studies included adults with type 2 diabetes using population stratification methods. The review protocol was registered on PROSPERO (ID: CRD42020206604) and conducted in line with PRISMA guidance. Extracted data included study aims; study setting (primary or secondary care); population characteristics; stratification variables and outcomes; and methodological approach to stratification.ResultsAcross 348 included studies, there were a total of 10,776,009 participants with a mean age of 61.0 years (SD 5.94). 6.7% of studies used data‐driven methods and the rest employed expert‐driven approaches using pre‐defined stratification criteria. The commonest variable used to stratify populations was HbA1c (n = 57, 16.4%); few studies stratified using clinically important non‐traditional variables such as health behaviours and beliefs.ConclusionsMost studies performing population stratification in type 2 diabetes used expert‐driven approaches with the aim of predicting outcomes in glycaemic control, mortality and cardiovascular complications. We identified relatively few studies using data‐driven approaches, which offer opportunities generate hypotheses beyond current expert knowledge. We describe important research gaps including stratification with regard to disease remission.
Hydrogen sulphide in liver glucose/lipid metabolism and non‐alcoholic fatty liver disease
Authors: Mateus Inês , Prip‐Buus Carina 
Published: September 2021

AbstractBackgroundFor a long time, hydrogen sulphide (H2S) was considered only as a toxic gas, inhibiting mitochondrial respiration at the level of cytochrome c oxidase, and an environmental pollutant. Nowadays, H2S is recognized as the third mammalian gasotransmitter, playing an important role in inflammation, septic shock, ischaemia reperfusion events, cardiovascular disease and more recently in liver physiology and chronic liver diseases such as non‐alcoholic fatty liver disease (NAFLD).MethodsThis narrative review is based on literature search using PubMed.ResultsFrom a bioenergetic perspective, H2S is a very unique molecule, serving as a mitochondrial poison at high concentrations or as an inorganic mitochondrial substrate at low concentrations. By using transgenic animal models to specifically modulate liver H2S biosynthesis or exogenous compounds that release H2S, several studies demonstrated that H2S is a key player in liver glucose and lipid metabolism. Liver H2S content and biosynthesis were also altered in NAFLD animal models with the in vivo administration of H2S‐releasing molecules preventing the further escalation into non‐alcoholic‐steatohepatitis. Liver steady‐state levels of H2S, and hence its cell signalling properties, are controlled by a tight balance between its biosynthesis, mainly through the transsulphuration pathway, and its mitochondrial oxidation via the sulphide oxidizing unit. However, studies investigating mitochondrial H2S oxidation in liver dysfunction still remain scarce.ConclusionsSince H2S emerges as a key regulator of liver metabolism and metabolic flexibility, further understanding the physiological relevance of mitochondrial H2S oxidation in liver energy homeostasis and its potential implication in chronic liver diseases are of great interest.
Micro‐climate correlations and conserved sexual dimorphism of cuticular hydrocarbons in European populations of the jewel wasp Nasonia vitripennis
Authors: Buellesbach Jan , Diao Wenwen , Schmitt Thomas , Beukeboom Leo W. 
Published: September 2021

1. Protection against desiccation and chemical communication are two fundamental functions of cuticular hydrocarbons (CHCs) in insects. In the parasitoid jewel wasp Nasonia vitripennis (Walker), characterised by a cosmopolitan distribution through largely different environments, CHCs function as universally recognised female sex pheromones. However, CHC uniformity as basis for sexual recognition may conflict with the desiccation protection function, expected to display considerable flexibility through adaptation to different environmental conditions.2. We compared male and female CHC profiles of N. vitripennis across a wide latitudinal gradient in Europe and correlated their CHC variation with climatic factors associated with desiccation. Additionally, we tested male mate discrimination behaviour between populations to detect potential variations in female sexual attractiveness.3. Results did not conform to the general expectation that longer, straight‐chain CHCs occur in higher proportions in warmer and drier climates. Instead, unexpected environmental correlations of intermediate chain‐length CHCs (C31) were found exclusively in females, potentially reflecting the different life histories of the sexes in N. vitripennis.4. Furthermore, we found no indication of population‐specific male mate preference, confirming the stability of female sexual attractiveness, likely conveyed through their CHC profiles. C31 mono‐ and C33 di‐methyl‐branched alkanes were consistently and most strongly associated with sexual dimorphism, suggesting their potential role in encoding the female‐specific sexual signalling function.5. Our study sheds light on how both adaptive flexibility and conserved sexual attractiveness can potentially be integrated and encoded in CHC profiles of N. vitripennis females across a wide distribution range in Europe.