bluuebunny/crossref_metadata_2025_split huggingface dataset:
RvD1 disrupts nociceptor neuron and macrophage activation and neuroimmune communication, reducing pain and inflammation in gouty arthritis in mice
Authors: Zaninelli Tiago H. , Fattori Victor , Saraiva‐Santos Telma , Badaro‐Garcia Stephanie , Staurengo‐Ferrari Larissa , Andrade Ketlem C. , Artero Nayara A. , Ferraz Camila R. , Bertozzi Mariana M. , Rasquel‐Oliveira Fernanda , Manchope Marilia F. , Amaral Flávio A. , Teixeira Mauro M. , Borghi Sergio M. , Rogers Michael S. , Casagrande Rubia , Verri Waldiceu A. 
Published: June 2022

Background and PurposeGouty arthritis is characterized by an intense inflammatory response to monosodium urate crystals (MSU), which induces severe pain. Current therapies are often ineffective in reducing gout‐related pain. Resolvin D1 (RvD1) is a specialized pro‐resolving lipid mediator with anti‐inflammatory and analgesic proprieties. In this study, we evaluated the effects and mechanisms of action of RvD1 in an experimental mouse model of gouty arthritis, an aim that was not pursued previously in the literature.Experimental ApproachMale mice were treated with RvD1 (intrathecally or intraperitoneally) before or after intraarticular stimulation with MSU. Mechanical hyperalgesia was assessed using an electronic von Frey aesthesiometer. Leukocyte recruitment was determined by knee joint wash cell counting and immunofluorescence. IL‐1β production was measured by ELISA. Phosphorylated NF‐kB and apoptosis‐associated speck‐like protein containing CARD (ASC) were detected by immunofluorescence, and mRNA expression was determined by RT‐qPCR. CGRP release was determined by EIA and immunofluorescence. MSU crystal phagocytosis was evaluated by confocal microscopy.Key ResultsRvD1 inhibited MSU‐induced mechanical hyperalgesia in a dose‐ and time‐dependent manner by reducing leukocyte recruitment and IL‐1β production in the knee joint. Intrathecal RvD1 reduced the activation of peptidergic neurons and macrophages as well as silenced nociceptor to macrophage communication and macrophage function. CGRP stimulated MSU phagocytosis and IL‐1β production by macrophages. RvD1 downmodulated this phenomenon directly by acting on macrophages, and indirectly by inhibiting CGRP release and CGRP‐dependent activation of macrophages.Conclusions and ImplicationsThis study reveals a hitherto unknown neuro‐immune axis in gouty arthritis that is targeted by RvD1.
Hippocampal neuroprotection mediated by secretome of human mesenchymal stem cells against experimental stroke
Authors: Asgari Taei Afsaneh , Dargahi Leila , Khodabakhsh Pariya , Kadivar Mehdi , Farahmandfar Maryam 
Published: June 2022

AbstractAimsRegenerative medicine literature has demonstrated that the therapeutic potentials of mesenchymal stem cells (MSCs) in experimental stroke are attributed to secreted bioactive factors rather than to cell replacement. Here, we explored the effects of secretome or conditioned medium (CM) derived from human embryonic stem cell‐derived MSCs (hESC‐MSCs) on hippocampal neurogenesis, inflammation, and apoptosis in experimental stroke.MethodsIschemic stroke was induced by right middle cerebral artery occlusion (MCAO) in male Wistar rats, and CM was infused either one time (1‐h post‐stroke; CM1) or three times (1‐, 24‐, and 48‐h post‐stroke; CM3) into left lateral ventricle. Neurogenesis markers (Nestin, Ki67, Doublecortin, and Reelin) were assessed at transcript and protein levels in the dentate gyrus of the hippocampus on day seven following MCAO. In parallel, changes in the gene expression of markers of apoptosis (Bax and Bim, as well as an anti‐apoptotic marker of Bcl2), inflammation (IL‐1β and IL‐6, as well as IL‐10 as an anti‐inflammatory cytokine), trophic factors (BDNF, GDNF, NGF, and NT‐3), and angiogenesis (CD31 and VEGF) in the hippocampus were assessed.ResultsOur results demonstrate that CM3 treatment could stimulate neurogenesis and angiogenesis concomitant with inhibition of inflammation, apoptosis, and neuronal loss in ischemic brains. Furthermore, rats treated with CM3 exhibited upregulation in neurotrophic factors.ConclusionOur results suggest that hESC‐MSC‐CM could promote neurogenesis and protect brain tissue from ischemic injury, partly mediated by induction of angiogenesis and neurotrophic factors and inhibition of inflammatory and apoptotic factors expression.
CircHIPK3 prevents chondrocyte apoptosis and cartilage degradation by sponging miR‐30a‐3p and promoting PON2
Authors: Shang Jie , Li Huizi , Wu Biao , Jiang Ning , Wang Bin , Wang Dawei , Zhong Junlong , Chen Yufeng , Xu Xianghe , Lu Huading 
Published: June 2022

AbstractOsteoarthritis (OA) is a common joint disease featured by the deterioration of articular cartilage and chondrocyte death. Emerging evidence has indicated that circular RNAs (circRNAs) play an essential role in OA progress. Here, we found that the expression of circHIPK3 was significantly decreased in human and mouse OA cartilage. Knocking down circHIPK3 increased apoptosis and intracellular ROS level in HC‐a chondrocytes. We performed proteomic studies and identified that circHIPK3 regulated chondrocyte apoptosis through the mitochondrial pathway. Results of JC‐1 staining and western blot further confirmed that mitochondrial outer membrane permeabilization was promoted in HC‐a chondrocytes transfected by circHIPK3 siRNA. In terms of mechanism, we showed that PON2 functioned as a potential target of circHIPK3 to regulate chondrocyte apoptosis. Moreover, we revealed that circHIPK3 interacted with miR‐30a‐3p to regulate PON2 expression in chondrocytes. Taken together, our findings suggested that circHIPK3 regulated chondrocyte apoptosis by mitochondrial pathway, and targeting the circHIPK3/miR‐30a‐3p/PON2 axis might be a potential strategy for OA treatment.
Sprouty1 exerts a preventive effect on the initiation of psoriasis by inhibiting innate immune antimicrobial peptide cathelicidin and immunocytes
Authors: Zhou Yuan , Wang Ping , Chen Xue‐Yan , Yan Bing‐Xi , Landeck Lilla , Wang Zhao‐Yuan , Xu Fan , Zheng Min , Man Xiao‐Yong 
Published: June 2022

AbstractObjectivesPsoriasis is an immune‐mediated skin disease dominated by the cutaneous immune system. Keratinocytes have been considered important triggers that initiate psoriasis. The key molecules and events of keratinocytes that link the innate immune system in psoriasis must be investigated in more detail. Human psoriasis skin and primary human keratinocyte were detected in vitro. Epidermis specific transgenic mouse strain (Krt14‐Sprouty1 tg) was used to further investigate psoriasis‐like skin inflammation in vivo.Materials and MethodsBulk RNA sequencing of primary human keratinocyte screened differentially expressed genes, which was confirmed by quantitative real time PCR and Western Blot (WB). Moreover, we concomitantly reviewed open‐accessed published RNAseq datasets of human psoriatic skin from GEO database. Immunohistochemical staining and immunofluorescence were used to detect Sprouty1 (SPRY1) expression in human psoriatic skin with and without anti‐psoriasis treatments. Krt14‐Sprouty1 tg was used to further investigate psoriasis‐like skin inflammation, and followed by Hematoxylin and Eosin (HE) Staining, enzyme linked immunosorbent assay (ELISA), Western Blot and flow cytometry.ResultsOur data showed that Sprouty1 was decreased in psoriatic skin and keratinocytes. In imiquimod‐induced psoriasis‐like skin inflammation, the production of cathelicidin (camp/LL37) was inhibited by suppressing signal transducer and activator of transcription3 (Stat3) activation when Sprouty1 overexpressed in mouse epidermal keratinocytes. Moreover, CD11b+CCR2+ dendritic cells, IL‐17A+ γδT cells, and Ly6C+ CD11c+ monocyte‐derived dendritic cells were decreased in Krt14‐Sprouty1 tg (STG) imiquimod‐induced cutaneous inflammation.ConclusionsThese findings indicate that Sprouty1 expressed in keratinocytes has a suppressive role in imiquimod‐induced skin inflammation mediated by inhibiting the production of cathelicidin. Collectively, Sprouty1 plays a preventive role in psoriatic skin. Our data provide new evidence for the pathogenesis of psoriatic keratinocytes, and the link cutaneous innate immunity, that indicated Sprouty1 is a potential novel therapeutic target.
Employment and ability to work after kidney transplantation in the Netherlands: The impact of preemptive versus non‐preemptive kidney transplantation
Authors: Visser Annemieke , Alma Manna A. , Bakker Stephan J. L. , Bemelman Frederike J. , Berger Stefan P. , van der Boog Paul J. M. , Brouwer Sandra , Hilbrands Luuk B. , Standaar Dorien S. M. , Stewart Roy E. , Gansevoort Ron T. 
Published: June 2022

AbstractBackgroundWork can have a major positive impact on health and wellbeing. Employment of kidney transplant recipients (KTR) of working age is much lower than in the general population. The first aim of this study was to examine the impact of a preemptive kidney transplantation (PKT) on employment, in addition to other possible influencing factors. The second aim was to explore differences in work ability, absenteeism and work performance among employed KTR with different types of transplantations.MethodsA cross‐sectional survey study was conducted between 2018 and 2019 in nine Dutch hospitals. PKT as potential predictor of employment was examined. Furthermore, work ability, absenteeism and loss of work performance were compared between employed preemptive recipients with a living donor (L‐PKT) and non‐preemptive recipients with a living donor (L‐nPKT) and with a deceased donor (D‐nPKT).ResultsTwo hundred and twenty four KTR participated; 71% reported having paid work. Paid work was more common among PKT recipients (82% vs. 65% in L‐nPKT and 55% in D‐nPKT) and recipients who were younger (OR .950, 95%CI .913–.989), had no comorbidities (1 comorbidity: OR .397, 95%CI .167–.942; 2 comorbidities: OR .347, 95%CI .142–.844), had less fatigue (OR .974, 95%CI .962–.987) and had mentally demanding work tasks (only in comparison with physically demanding tasks, OR .342, 95%CI .145–.806). If recipients were employed, D‐nPKT recipients worked fewer hours (mean 24.6±11.3 vs. PKT 31.1±9.6, L‐nPKT 30.1±9.5) and D‐nPKT and L‐nPKT recipients received more often supplemental disability benefits (32 and 33.3%, respectively) compared to PKT recipients (9.9%). No differences were found for self‐reported ability to work, sick leave (absenteeism) and loss of work performance with the exception of limitations in functioning at work.ConclusionsPreemptive kidney transplantation recipients with a kidney from a living donor are employed more often, work more hours per week (only in comparison with D‐nPKT) and have a partial disability benefit less often than nPKT recipients. More knowledge regarding treatments supporting sustainable participation in the labor force is needed as work has a positive impact on recipients’ health and wellbeing and is also beneficial for society as a whole.
Developmental temperature predicts body size, flight, and pollen load in a widespread butterfly
Authors: Büyükyilmaz Erez , Tseng Michelle 
Published: June 2022

Abstract
Most of our understanding of the effects of climate warming on insect body size comes from laboratory experiments. Whether these studies predict patterns in nature is largely unknown.
Here we examine the relevance of laboratory warming experiments for wild populations of the butterfly Pieris rapae. We tested two predictions: (i) butterflies reared at warmer temperatures in the laboratory should attain smaller adult sizes and have reduced flight ability, and (ii) in nature, this trait combination should lead to smaller butterflies visiting fewer flowers and accumulating less pollen.
Overall, we found that warm‐reared butterflies were indeed smaller and flew more slowly compared to colder‐reared conspecifics. Additionally, wild‐caught small butterflies carried fewer, and a lower diversity of pollen grains compared to larger butterflies.
Our warming experiments thus largely predicted pollen collection patterns in wild P. rapae.
This study demonstrates that increased temperatures will likely have important consequences for butterfly‐plant interactions in nature.
How agency and self‐efficacy moderate the effects of strategic improvisational behaviors on sales performance: Evidence from an emerging market
Authors: Hultman Magnus , Boso Nathaniel , Yeboah‐Banin Abena Animwaa , Hodgkinson Ian , Souchon Anne L. , Nemkova Ekaterina , Oliveira Joao , Hughes Paul 
Published: June 2022

AbstractThis study develops and tests arguments that improvisation is not universal in its benefits for the firm, but rather its multidimensional characteristics (action‐orientation, creativity, and spontaneity) hold differential performance effects. The study further examines whether these relationships are contingent upon individual agency and self‐efficacy. Drawing on primary data from industrial sales account managers in Ghana, the study finds that an increasing level of action‐orientation is associated with decreases in perceived sales performance and the decrease in performance is more pronounced under conditions of stronger sense of agency and self‐efficacy. Similarly, an increasing level of creativity is associated with decreases in perceived sales performance when agency is stronger. However, an increasing level of spontaneity is associated with increases in performance and this increase is strengthened under conditions of stronger sense of self‐efficacy. The study concludes that the effect of strategic improvisation on sales performance outcome within the context of an emerging economy (such as Ghana) is more nuanced than established improvisation literature suggests.
Anti‐CD20 therapy for multiple sclerosis‐associated uveitis: A case series
Authors: Stascheit Frauke , Rübsam Anne , Otto Carolin , Meisel Andreas , Ruprecht Klemens , Pleyer Uwe 
Published: June 2022

AbstractBackground and purposeApproximately 1% of patients with multiple sclerosis (MS) have uveitis, but data on the effects of immunotherapies for MS on MS‐associated uveitis are scarce. The aim of this study was to investigate the ophthalmological outcomes in patients with MS‐associated uveitis treated with anti‐CD20 therapy.MethodsA retrospective study of 12 eyes of six patients with MS‐associated uveitis, refractory to previous immunotherapies, was conducted. Uveitis activity was assessed before initiation of anti‐CD20 therapy and at regular follow‐up visits. Primary outcome measures were: vitreous haze score; retinal vasculitis score, determined on fluorescein angiography images; macular edema, as quantified by central retinal thickness (CRT) on optical coherence tomography; and visual acuity (VA). Secondary outcomes included number of annualized uveitis or MS relapses, disease activity on cerebral magnetic resonance imaging (cMRI) and Expanded Disability Status Scale (EDSS) score.ResultsAfter a median (interquartile range [IQR]) treatment time of 28.5 (8–43) months, anti‐CD20 therapy was associated with an improvement of vitreous haze score (p = 0.002), retinal vasculitis score (p = 0.001), CRT (p = 0.002), and VA (p = 0.007). The median (IQR) annualized uveitis relapse rate declined from 0.59 (0.56–0.94) before to 0 (0–0.49) after the start of anti‐CD20 therapy. The median (IQR) annualized MS relapse rate declined from 0.62 (0.26–2.84) before to 0 (0–0) after the start of anti‐CD20 therapy. After initiation of anti‐CD20 therapy, there was no disease activity on cMRI, and EDSS score improved (n = 2) or remained stable (n = 4). No severe adverse events were observed.ConclusionThese findings suggest that anti‐CD20 therapy may be a valuable treatment option for MS‐associated uveitis.
Precision medicine for genetic epilepsy on the horizon: Recent advances, present challenges, and suggestions for continued progress
Authors: Knowles Juliet K. , Helbig Ingo , Metcalf Cameron S. , Lubbers Laura S. , Isom Lori L. , Demarest Scott , Goldberg Ethan M. , George Alfred L. , Lerche Holger , Weckhuysen Sarah , Whittemore Vicky , Berkovic Samuel F. , Lowenstein Daniel H. 
Published: June 2022

AbstractThe genetic basis of many epilepsies is increasingly understood, giving rise to the possibility of precision treatments tailored to specific genetic etiologies. Despite this, current medical therapy for most epilepsies remains imprecise, aimed primarily at empirical seizure reduction rather than targeting specific disease processes. Intellectual and technological leaps in diagnosis over the past 10 years have not yet translated to routine changes in clinical practice. However, the epilepsy community is poised to make impressive gains in precision therapy, with continued innovation in gene discovery, diagnostic ability, and bioinformatics; increased access to genetic testing and counseling; fuller understanding of natural histories; agility and rigor in preclinical research, including strategic use of emerging model systems; and engagement of an evolving group of stakeholders (including patient advocates, governmental resources, and clinicians and scientists in academia and industry). In each of these areas, we highlight notable examples of recent progress, new or persistent challenges, and future directions. The future of precision medicine for genetic epilepsy looks bright if key opportunities on the horizon can be pursued with strategic and coordinated effort.
Cardiovascular disease prediction using recursive feature elimination and gradient boosting classification techniques
Authors: Theerthagiri Prasannavenkatesan , Vidya Jyothiprakash 
Published: June 2022

AbstractCardiovascular diseases are one of the most common chronic illnesses that affect people's health. Early detection of cardiovascular diseases's can reduce mortality rates by preventing or reducing the severity of the disease. Machine learning algorithms are a promising method for identifying risk factors. This article proposes a recursive feature elimination‐based gradient boosting algorithm in order to obtain accurate heart disease prediction. The patients' health record with important cardiovascular disease features has been analysed for the evaluation of the results. Several other machine learning methods were also used to build the prediction model, and the results were compared with the proposed model. The results of this proposed model infer that the combined recursive feature elimination and gradient boosting algorithm achieves the highest accuracy (89.7%). Further, with an area under the curve of 0.84, the proposed algorithm was found superior and had obtained a substantial gain over other techniques. Thus, the proposed gradient boosting algorithm will serve as a prominent cardiovascular disease estimation and treatment model.
Benzimidazole derivatives: A versatile scaffold for drug development against Helicobacter pylori‐related diseases
Authors: Rostami Hedieh , Haddadi Mohammad Hossein 
Published: June 2022

AbstractHelicobacter pylori (H. pylori) is a microaerophilic gastric pathogen and a major contributor to chronic atrophic gastritis, peptic ulcer, and gastric malignancies. The increasing prevalence of H. pylori infection and its related diseases, such as gastric cancer (GC), motivates medicinal chemists to seek for more effective multi‐targeting drugs to prevent and treat H. pylori‐related clinical complications. Benzimidazole, a hetero‐aromatic bicyclic ring compound, has claimed a prominent role in medicinal chemistry owing to its broad range of biological activities, including antibacterial, antiviral, antidiabetic, and anticancer activities. Studies highlight the promising therapeutic potential of benzimidazole derivatives in the treatment of H. pylori‐related clinical complications such as gastric infection, gastritis, peptic ulcer, and GC. Accordingly, we here aimed to scrutinize the role of active molecules of benzimidazole derivatives as potential antibacterial, anti‐urease, anti‐inflammatory, anti‐ulcerative, and anticancer agents, which are expected to find their ways to the clinical setting sooner or later. Due to the role of structural moieties in determining the biological behaviors of benzimidazole derivatives, we explored the structure–activity relationship (SAR) of these compounds to further expand the scope of design of and research on new drugs against H. pylori‐related diseases.
Copper mobilisation from Cu sulphide minerals by methanobactin: Effect of pH, oxygen and natural organic matter
Authors: Rushworth Danielle D. , Christl Iso , Kumar Naresh , Hoffmann Kevin , Kretzschmar Ruben , Lehmann Moritz F. , Schenkeveld Walter D. C. , Kraemer Stephan M. 
Published: June 2022

AbstractAerobic methane oxidation (MOx) depends critically on the availability of copper (Cu) as a crucial component of the metal centre of particulate methane monooxygenase, one of the main enzymes involved in MOx. Some methanotrophs have developed Cu acquisition strategies, in which they exude Cu‐binding ligands termed chalkophores under conditions of low Cu availability. A well‐characterised chalkophore is methanobactin (mb), exuded by the microaerophilic methanotroph Methylosinus trichosporium OB3b. Aerobic methanotrophs generally reside close to environmental oxic–anoxic interfaces, where the formation of Cu sulphide phases can aggravate the limitation of bioavailable Cu due to their low solubility. The reactivity of chalkophores towards such Cu sulphide mineral phases has not yet been investigated. In this study, a combination of dissolution experiments and equilibrium modelling was used to examine the dissolution and solubility of bulk and nanoparticulate Cu sulphide minerals in the presence of mb as influenced by pH, oxygen and natural organic matter. In general, we show that mb is effective at increasing the dissolved Cu concentrations in the presence of a variety of Cu sulphide phases that may potentially limit Cu bioavailability. More Cu was mobilised per mole of mb from Cu sulphide nanoparticles compared with well‐crystalline bulk covellite (CuS). In general, the efficacy of mb at mobilising Cu from Cu sulphides is pH‐dependent. At lower pH, e.g. pH 5, mb was ineffective at solubilizing Cu. The presence of mb increased dissolved Cu concentrations between pH 7 and 8.5, where the solubility of all Cu sulphides is generally low, both in the presence and absence of oxygen. These results suggest that chalkophore‐promoted Cu mobilisation from sulphide phases is an effective extracellular mechanism for increasing dissolved Cu concentrations at oxic–anoxic interfaces, particularly in the neutral to slightly alkaline pH range. This suggests that aerobic methanotrophs may be able to fulfil their Cu requirements via the exudation of mb in natural environments where the bioavailability of Cu is constrained by very stable Cu sulphide phases.