bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zinc restores functionality in porcine prepubertal Sertoli cells exposed to subtoxic cadmium concentration via regulating the Nrf2 signaling pathway
Authors: Mancuso Francesca , Arato Iva , Bellucci Catia , Lilli Cinzia , Eugeni Elena , Aglietti Maria Chiara , Stabile Anna Maria , Pistilli Alessandra , Brancorsini Stefano , Gaggia Francesco , Calvitti Mario , Baroni Tiziano , Luca Giovanni 
Published: February 2023

IntroductionAmong substances released into the environment by anthropogenic activities, the heavy metal cadmium (Cd) is known to induce severe testicular injury causing male subfertility/infertility. Zinc (Zn) is another heavy metal that, unlike Cd, is physiologically present in the testis, being essential for spermatogenesis. We aimed to examine the possibility that 50 µM ZnCl2 could counteract the toxic effects induced by Cd in an in vitro model of porcine prepubertal Sertoli cells (SCs) exposed to both subtoxic (5 μM) and toxic (10 μM) concentrations of CdCl2 for 48 h.Materials and MethodsApoptosis, cell cycle, and cell functionality were assessed. The gene expression of Nrf2 and its downstream antioxidant enzymes, ERK1/2, and AKT kinase signaling pathways were evaluated.Materials and ResultsWe found that Zn, in co-treatment with subtoxic and toxic Cd concentration, increased the number of metabolically active SCs compared to Cd exposure alone but restored SC functionality only in co-treatment with subtoxic Cd concentration with respect to subtoxic Cd alone. Exposure of Cd disrupted cell cycle in SCs, and Zn co-treatment was not able to counteract this effect. Cd alone induced SC death through apoptosis and necrosis in a dose-dependent manner, and co-treatment with Zn increased the pro-apoptotic effect of Cd. Subtoxic and toxic Cd exposures activated the Nrf2 signaling pathway by increasing gene expression of Nrf2 and its downstream genes (SOD, HO-1, and GSHPx). Zn co-treatment with subtoxic Cd attenuated upregulation on the Nrf2 system, while with toxic Cd, the effect was more erratic. Studying ERK1/2 and AKT pathways as a target, we found that the phosphorylation ratio of p-ERK1/2 and p-AKT was upregulated by both subtoxic and toxic Cd exposure alone and in co-treatment with Zn.DiscussionOur results suggest that Zn could counteract Cd effects by increasing the number of metabolically active SCs, fully or partially restoring their functionality by modulating Nrf2, ERK1/2, and AKT pathways. Our SC model could be useful to study the effects of early Cd exposure on immature testis, evaluating the possible protective effects of Zn.
Managing an invasive tree in coastal dunes: The importance of follow-up treatments to improve the recovery of protected habitats
Authors: Duarte Liliana Neto , Marchante Elizabete , Marchante Hélia 
Published: February 2023

Conservation of biodiversity in protected areas is often threatened by invasive alien plants (IAPs), and its successful management requires proper planning, resources, and monitoring to adjust future interventions. Although follow-up controls and evaluation of different management actions through monitoring programs are crucial in an adaptive management strategy, they are often neglected.Acacia longifoliais one of the most widespread IAPs in the Portuguese coastal areas, causing several negative impacts. This study reports the results of different control methods ofA. longifoliain two forest plantations over coastal dunes in two protected sites in Portugal, under different management regimes and for over 4 years. The best results were achieved after hand pulling, but due to its high cost, this method is not suitable for large areas. Mechanical cuts, which include the use of brush hogs, brush cutters, and chainsaws, resulted in variable levels of resprouting ofA. longifoliastumps. Follow-up treatments, whether mechanical and/or chemical, reduced the number ofA. longifoliaresprouts and kept its cover below 20% and height below 50 cm. Furthermore, controlling with brush cutters/hogs reduced the seed bank ofA. longifoliaby 74% while that with a disc harrow allowed an even greater reduction (91%). In areas where no follow-up treatments were carried out,A. longifoliastarted producing flowers two and a half years after the initial treatment, restarting the cycle of seed production. Nevertheless, a biological control agent that reducesA. longifoliaseed production (Trichilogaster acaciaelongifoliae) establishment was confirmed in the controlled areas, suggesting that new seed production by these plants will be soon controlled. Although species characteristic of the protected habitats are currently poorly represented, it is expected that they begin to emerge with the reduction ofA. longifolia. Our results stress the importance of persistence of follow-up treatments if higher success in IAPs control is to be achieved, not only because of the resprouting ability of many species (despite this not being very common inA. longifolia) but also because invasive plants can produce extensive persistent seed banks. The role of the management regime on the level of success in controlling IAPs will be discussed.
Partial SAA patients benefit from delayed response of IST
Authors: Wang Ting , Wang Chaomeng , Liu Chunyan , Shao Zonghong , Fu Rong 
Published: February 2023

IntroductionSevere aplastic anemia(SAA)is a severe disease characterized by immune-mediated bone marrow failure and pancytopenia. Immunosuppressive therapy (ATG plus CsA, IST) is the standard treatment for patients who are not suitable for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Some patients have a delayed response after 6 months of ATG, and unnecessary to be given secondary ATG or allo-HSCT. We attempted to distinguish patients who may get potential delayed response from those who were really not responsive to IST.MethodsWe collected data from 45 SAA patients who were assessed no-response to IST at 6 months after rATG and failed to receive secondary ATG or allo-HSCT.ResultsCsA plus eltrombopag (EPAG) group has an extra 75% response rate while CsA maintenance group has an extra 44% response rate at 12 months. ATG was applied within 30 days after diagnosis, ATG dosage was suffificient (ATG/lymphocyte ≥2), and absolute reticulocyte count (ARC) was ≥30×109 /L at 6 months, indicated patients could get delayed response and benefifit from CsA maintenance. Addition of EPAG could give an even better response. Otherwise, secondary ATG or allo-HSCT treatment were recommended to be given immediately.Clinical Trial Registrationhttps://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR2300067615.
Specific in situ immuno-imaging of pulmonary-resident memory lymphocytes in human lungs
Authors: Humphries Duncan C. , O’Connor Richard A. , Stewart Hazel L. , Quinn Tom M. , Gaughan Erin E. , Mills Beth , Williams Gareth O.S. , Stone James M. , Finlayson Keith , Chabaud-Riou Martine , Boudet Florence , Dhaliwal Kevin , Pavot Vincent 
Published: February 2023

IntroductionPulmonary-resident memory T cells (TRM) and B cells (BRM) orchestrate protective immunity to reinfection with respiratory pathogens. Developing methods for the in situ detection of these populations would benefit both research and clinical settings.MethodsTo address this need, we developed a novel in situ immunolabelling approach combined with clinic-ready fibre-based optical endomicroscopy (OEM) to detect canonical markers of lymphocyte tissue residency in situ in human lungs undergoing ex vivo lung ventilation (EVLV).ResultsInitially, cells from human lung digests (confirmed to contain TRM/BRM populations using flow cytometry) were stained with CD69 and CD103/CD20 fluorescent antibodies and imaged in vitro using KronoScan, demonstrating it’s ability to detect antibody labelled cells. We next instilled these pre-labelled cells into human lungs undergoing EVLV and confirmed they could still be visualised using both fluorescence intensity and lifetime imaging against background lung architecture. Finally, we instilled fluorescent CD69 and CD103/CD20 antibodies directly into the lung and were able to detect TRM/BRM following in situ labelling within seconds of direct intra-alveolar delivery of microdoses of fluorescently labelled antibodies.DiscussionIn situ, no wash, immunolabelling with intra-alveolar OEM imaging is a novel methodology with the potential to expand the experimental utility of EVLV and pre-clinical models.
Suppression of MR1 by human cytomegalovirus inhibits MAIT cell activation
Authors: Ashley Caroline L. , McSharry Brian P. , McWilliam Hamish E. G. , Stanton Richard J. , Fielding Ceri A. , Mathias Rommel A. , Fairlie David P. , McCluskey James , Villadangos Jose A. , Rossjohn Jamie , Abendroth Allison , Slobedman Barry 
Published: February 2023

IntroductionThe antigen presentation molecule MHC class I related protein-1 (MR1) is best characterized by its ability to present bacterially derived metabolites of vitamin B2 biosynthesis to mucosal-associated invariant T-cells (MAIT cells).MethodsThrough in vitro human cytomegalovirus (HCMV) infection in the presence of MR1 ligand we investigate the modulation of MR1 expression. Using coimmunoprecipitation, mass spectrometry, expression by recombinant adenovirus and HCMV deletion mutants we investigate HCMV gpUS9 and its family members as potential regulators of MR1 expression. The functional consequences of MR1 modulation by HCMV infection are explored in coculture activation assays with either Jurkat cells engineered to express the MAIT cell TCR or primary MAIT cells. MR1 dependence in these activation assays is established by addition of MR1 neutralizing antibody and CRISPR/Cas-9 mediated MR1 knockout.ResultsHere we demonstrate that HCMV infection efficiently suppresses MR1 surface expression and reduces total MR1 protein levels. Expression of the viral glycoprotein gpUS9 in isolation could reduce both cell surface and total MR1 levels, with analysis of a specific US9 HCMV deletion mutant suggesting that the virus can target MR1 using multiple mechanisms. Functional assays with primary MAIT cells demonstrated the ability of HCMV infection to inhibit bacterially driven, MR1-dependent activation using both neutralizing antibodies and engineered MR1 knockout cells.DiscussionThis study identifies a strategy encoded by HCMV to disrupt the MR1:MAIT cell axis. This immune axis is less well characterized in the context of viral infection. HCMV encodes hundreds of proteins, some of which regulate the expression of antigen presentation molecules. However the ability of this virus to regulate the MR1:MAIT TCR axis has not been studied in detail.
A case report of neuronal intranuclear inclusion disease with paroxysmal peripheral neuropathy-like onset lacking typical signs on diffusion-weighted imaging
Authors: Fu Jiayu , Zhao Chen , Hou Guanghao , Liu Xiaoxuan , Zheng Mei , Zhang Yingshuang , Zhang Shuo , Zheng Danfeng , Zhang Yixuan , Huang Xiao , Ye Shan , Fan Dongsheng 
Published: February 2023

BackgroundNeuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions and the GGC repeats in the 5'-untranslated region of NOTCH2NLC. The prevalent presence of high-intensity signal along the corticomedullary junction on diffusion-weighted imaging (DWI) helps to recognize this heterogeneous disease despite of highly variable clinical manifestations. However, patients without the typical sign on DWI are often misdiagnosed. Besides, there are no reports of NIID patients presenting with paroxysmal peripheral neuropathy-like onset to date.Case presentationWe present a patient with NIID who suffered recurrent transient numbness in arms for 17 months. Magnetic resonance imaging (MRI) showed diffuse, bilateral white matter lesions without typical subcortical DWI signals. Electrophysiological studies revealed mixed demyelinating and axonal sensorimotor polyneuropathies involving four extremities. After excluding differential diagnosis of peripheral neuropathy through body fluid tests and a sural nerve biopsy, NIID was confirmed by a skin biopsy and the genetic analysis of NOTCH2NLC.ConclusionThis case innovatively demonstrates that NIID could manifest as paroxysmal peripheral neuropathy-like onset, and addresses the electrophysiological characteristics of NIID in depth. We broaden the clinical spectrum of NIID and provide new insights into its differential diagnosis from the perspective of peripheral neuropathy.
People solve rebuses unwittingly—Both forward and backward: Empirical evidence for the mental effectiveness of the signifier
Authors: Olyff Giulia , Bazan Ariane 
Published: February 2023

IntroductionFreud proposed that names of clinically salient objects or situations, such as for example a beetle (Käfer) in Mr. E’s panic attack, refer through their phonological word form, and not through their meaning, to etiologically important events—here, “Que faire?” which summarizes the indecisiveness of Mr. E’s mother concerning her marriage with Mr. E’s father. Lacan formalized these ideas, attributing full-fledged mental effectiveness to the signifier, and summarized this as “the unconscious structured as a language”. We tested one aspect of this theory, namely that there is an influence of the ambiguous phonological translation of the world upon our mental processing without us being aware of this influence.MethodsFor this, we used a rebus priming paradigm, including 14 French rebuses, composed of two images depicting common objects, such as paon /pã/ “peacock” and terre /tεr/ “earth,” together forming the rebus panthère /pãtεr/ “panther.” These images were followed by a target word semantically related to the rebus resolution, e.g., félin “feline,” upon which the participants, unaware of the rebus principle, produced 6 written associations. A total of 1,458 participants were randomly assigned either to Experiment 1 in which they were shown the rebus images in either forward or in reverse order or to Experiment 2, in which they were shown only one of both rebus images, either the first or the last.Results and discussionThe results show that the images induced inadvertent rebus priming in naïve participants. In other words, our results show that people solve rebuses unwittingly independent of stimulus order, thereby constituting empirical evidence for the mental effectiveness of the signifier.
A clinical prediction model for lung metastasis risk in osteosarcoma: A multicenter retrospective study
Authors: Zheng Shengping , Chen Longhao , Wang Jiaming , Wang Haosheng , Hu Zhaohui , Li Wanying , Xu Chan , Ma Minmin , Wang Bing , Huang Yangjun , Liu Qiang , Tang Zhi-Ri , Liu Guanyu , Wang Tingting , Li Wenle , Yin Chengliang 
Published: February 2023

BackgroundLung metastases (LM) have a poor prognosis of osteosarcoma. This study aimed to predict the risk of LM using the nomogram in patients with osteosarcoma.MethodsA total of 1100 patients who were diagnosed as osteosarcoma between 2010 and 2019 in the Surveillance, Epidemiology and End Results (SEER) database were selected as the training cohort. Univariate and multivariate logistic regression analyses were used to identify independent prognostic factors of osteosarcoma lung metastases. 108 osteosarcoma patients from a multicentre dataset was as valiation data. The predictive power of the nomogram model was assessed by receiver operating characteristic curves (ROC) and calibration plots, and decision curve analysis (DCA) was utilized to interpret the accurate validity in clinical practice.ResultsA total of 1208 patients with osteosarcoma from both the SEER database(n=1100) and the multicentre database (n=108) were analyzed. Univariate and multivariate logistic regression analyses showed that Survival time, Sex, T-stage, N-stage, Surgery, Radiation, and Bone metastases were independent risk factors for lung metastasis. We combined these factors to construct a nomogram for estimating the risk of lung metastasis. Internal and external validation showed significant predictive differences (AUC 0.779, 0.792 respectively). Calibration plots showed good performance of the nomogram model.ConclusionsIn this study, a nomogram model for predicting the risk of lung metastases in osteosarcoma patients was constructed and turned out to be accurate and reliable through internal and external validation. Moreover we built a webpage calculator (https://drliwenle.shinyapps.io/OSLM/) taken into account nomogram model to help clinicians make more accurate and personalized predictions.
99mTc-rituximab tracer injection for guiding internal mammary sentinel lymph nodes biopsy in primary breast cancer: A prospective observational study
Authors: Chen Wenxin , Su Yaodong , Zhang Hui , Zhang Yu , Zhu Lin , Lin Mengbo , Lin Zhiyi , Yu Mingdian , Yang Shengping , Zhang Yanmin 
Published: February 2023

ObjectiveTo explore the use of 99mTc-rituximab tracer injection for internal mammary sentinel lymph node (IM-SLN) detection in patients with primary breast cancer.MethodsThis prospective observational study enrolled female patients with primary breast cancer between September 2017 and June 2022 at Fujian Provincial Hospital. The participants were divided into the peritumoral group (two subcutaneous injection points on the surface of the tumor), two-site group (injections into the glands at 6 and 12 o’clock around the areola area), and four-site group (injections into the gland at 3, 6, 9, and 12 o’clock around the areola area). The outcomes were the detection rates of the IM-SLNs and axillary sentinel lymph nodes (A-SLNs).ResultsFinally, 133 patients were enrolled, including 53 in the peritumoral group, 60 in the two-site group, and 20 in the four-site group. The detection rate of the IM-SLNs in the peritumoral group (9.4% [5/53]) was significantly lower than in the two-site (61.7% [37/60], P&lt;0.001) and four-site (50.0% [10/20], P&lt;0.001) groups. The detection rates of A-SLNs among the three groups were comparable (P=0.436).ConclusionThe two-site or four-site intra-gland injection of 99mTc-rituximab tracer might achieve a higher detection rate of IM-SLNs and a comparable detection rate of A-SLNs compared with the peritumoral method. The location of the primary focus has no impact on the detection rate of the IM-SLNs.
The safety and efficacy of remimazolam tosylate for induction and maintenance of general anesthesia in pediatric patients undergoing elective surgery: Study protocol for a multicenter, randomized, single-blind, positive-controlled clinical trial
Authors: Fang Yu-Bo , Wang Cheng-Yu , Gao Yu-Qing , Cai Yu-Hang , Chen Jia , Zhang Xu-Lin , Dong Le-Qi , Shang-Guan Wang-Ning , Liu Hua-Cheng 
Published: February 2023

Introduction: Remimazolam is an ultra-short-acting benzodiazepine sedative agent commonly used in general anesthesia, procedural sedation, and intensive care unit (ICU) sedation. This study aimed to explore the efficacy and safety of remimazolam versus propofol for the induction and maintenance of general anesthesia in preschool-age children undergoing elective surgery.Methods and analysis: In this multicenter, randomized, single-blind, positive-controlled non-inferior clinical trial, one hundred ninety-two children aged 3–6 years will be randomly allocated as a 3:1 ratio into two groups: Group R with an intravenous dose of remimazolam 0.3 mg/kg for the induction of anesthesia followed by a constant infusion rate of remimazolam 1–3 mg/kg/h to maintain anesthesia, and Group P with an intravenous dose of propofol 2.5 mg/kg for the induction of anesthesia followed by a constant infusion rate of propofol 4–12 mg/kg/h to maintain anesthesia. The primary outcome will be the rate of the successful induction and maintenance of anesthesia. The secondary outcomes will include the time to LoC, the Bispectral Index (BIS) value, awakening time, extubation time, post-anesthesia care unit (PACU) discharge time, usage of additional sedative drugs during the induction period, usage of remedial drugs in PACU, emergence delirium, pain in PACU, behavior scores at day 3 after surgery, parental and anesthesiologists’ satisfaction, and adverse events.Ethics and dissemination: This study has been approved by the ethics review boards at all participating hospitals. The Ethics Committee of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University (Reference No. LCKY 2020-380, November 13, 2020) is the central ethics committee.
Prevalence and global trends of polypharmacy in patients with chronic kidney disease: A systematic review and meta-analysis
Authors: Naseralallah Lina , Khatib Malkan , Al-Khulaifi Azhar , Danjuma Mohammed 
Published: February 2023

Background and objectives: Polypharmacy and chronic kidney disease (CKD) are becoming increasingly common due to an ageing population and the rise of multimorbidity. In line with the therapeutic guidelines, managing CKD and its complications necessitates prescribing multiple medications, which predisposes patients to polypharmacy. The aim of this systematic review and meta-analysis is to describe the prevalence of polypharmacy in patients with CKD and to explore the global trends of factors driving any apparent variability in prevalence estimates.Methods: PubMed, Scopus, the Cochrane Database of Systematic Reviews (CDSR), and Google Scholar were searched from 1999 to November 2021. Study selection, data extraction, and critical appraisal were conducted by two independent reviewers. The pooled prevalence of polypharmacy was estimated utilizing the random effects model using the default double arcsine transformation.Results: This review involved 14 studies comprising of 17 201 participants, a significant proportion of which were males (56.12%). The mean age of the review population was 61.96 (SD ± 11.51) years. The overall pooled prevalence of polypharmacy amongst patients with CKD was 69% (95% CI: 49%–86%) (I2 = 100%, p &lt; 0.0001), with a proportionately higher prevalence in North America and Europe as compared to Asia.Conclusion: The results from this meta-analysis showed a high pooled prevalence estimates of polypharmacy amongst patient cohorts with CKD. The exact interventions that are likely to significantly mitigate its effect remain uncertain and will need exploration by future prospective and systematic studies.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022306572].