bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alemtuzumab‐induced petechiae and epistaxis in a patient with relapsing–remitting multiple sclerosis: A case report
Authors: Mahmoudi Farhad , Emami Sayed Ali , Masaeli Farid , Rayatpisheh Najmeh 
Published: November 2023

Key clinical messageHere, we present a case of relapsing–remitting multiple sclerosis that experienced petechiae and epistaxis following treatment with second dose of alemtuzumab. This study highlights such effects, emphasizing the need for vigilance as alemtuzumab usage increases. Timely recognition and management are vital for patient care.
Application of a dried blood spot based proteomic and genetic assay for diagnosing hereditary angioedema
Authors: Iuraşcu Marius‐Ionuţ , Balla Zsuzsanna , Pereira Catarina , Andrási Noémi , Varga Lilian , Csuka Dorottya , Szilágyi Ágnes , Tripolszki Kornelia , Khan Suliman , Susnea Iuliana , Bauer Peter , Cozma Claudia , Farkas Henriette 
Published: November 2023

AbstractBackgroundHereditary angioedema (HAE) with C1‐inhibitor deficiency (C1‐INH‐HAE) is a rare disease caused by low level (type I) or dysfunction (type II) of the C1‐inhibitor protein with subsequent reduction of certain complement protein levels.MethodsTo develop and test the reliability of a two‐tier method based on C1‐INH and C4 quantitation followed by genetic analysis from dried blood spot (DBS) for establishing the diagnosis of C1‐INH‐HAE. C1‐INH and C4 proteins have been quantified in human plasma using a classical immuno‐assay and in DBS using a newly developed proteolytic liquid chromatography–mass spectrometry method. Genetic analysis was carried out as reported previously (PMID: 35386643) and by a targeted next‐generation sequencing panel, multiplex ligation‐dependent probe amplification and in some cases whole genome sequencing.ResultsDBS quantification of C1‐INH and C4 showed the same pattern as plasma, offering the possibility of screening patients with AE symptoms either locally or remotely. Genetic analysis from DBS verified each of the previously identified SERPING1 mutations of the tested C1‐INH‐HAE patients and revealed the presence of other rare variations in genes that may be involved in the pathogenesis of AE episodes.ConclusionsC1‐INH/C4 quantification in DBS can be used for screening of hereditary AE and DNA extracted from dried blood spots is suitable for identifying various types of mutations of the SERPING1 gene.
Diabetes mellitus in long‐term survivors with colorectal, breast, or prostate cancer: Prevalence and prognosis. A population‐based study
Authors: Yang Keyi , Doege Daniela , Thong Melissa S. Y. , Koch‐Gallenkamp Lena , Weisser Linda , Bertram Heike , Eberle Andrea , Holleczek Bernd , Nennecke Alice , Waldmann Annika , Zeissig Sylke Ruth , Pritzkuleit Ron , Jansen Lina , Brenner Hermann , Arndt Volker 
Published: November 2023

AbstractBackgroundPatients with cancer are at increased risk of diabetes mellitus (DM). Previous studies on the prevalence and prognostic impact of DM in cancer survivors were limited by small sample sizes or short follow‐up times. We aimed to compare the patient‐reported prevalence of DM in long‐term cancer survivors (LTCS), who survived 5 years or more after cancer diagnosis, with that in cancer‐free controls, and to estimate the mortality risk among LTCS according to DM status.MethodsOur population‐based cohort comprised 6952 LTCS diagnosed with breast, colorectal, or prostate cancer between 1994 and 2004, recruited in 2008–2011 (baseline), and followed until 2019. A total of 1828 cancer‐free individuals served as controls. Multivariable logistic regression was used to compare the prevalence of DM in LTCS and controls, and according to covariates at baseline. Mortality among LTCS according to DM was assessed by Cox proportional hazards regression.ResultsA total of 962 (13.8%) LTCS at baseline reported DM. Prevalence of DM in LTCS was not higher than in cancer‐free controls, both at baseline (odds ratio, 0.80; 95% CI, 0.66–0.97) and at follow‐up (odds ratio, 0.83; 95% CI, 0.67–1.04). Prevalence of DM in LTCS was associated with cancer site, older age, lower education, higher socioeconomic deprivation, higher body mass index, physical inactivity, other comorbidities, and poorer prognosis (adjusted hazard ratio [all‐cause mortality] = 1.29; 95% CI, 1.15–1.44).ConclusionDM in LTCS is prevalent, but not higher than in cancer‐free population controls. Cancer survivors with concurrent DM are at a potentially higher risk of death.Plain Language Summary

Cancer and diabetes mellitus (DM) are two serious threats to global health.
In our study, prevalence of DM in long‐term cancer survivors who survived 5 years or more after cancer diagnosis was not higher than in cancer‐free controls.
This should not be interpreted as an indication of a lower risk of DM in cancer survivors. Rather, it highlights the potentially poor prognosis in diabetic cancer survivors. Therefore, keeping a continuous satisfactory DM and hyperglycemia management is essential during long‐term cancer survivorship.
Prognostic value of red blood cell distribution width and D‐Dimer in diffuse large B‐cell lymphoma: Systematic review and meta‐analysis
Authors: Rahchamani Maryam , Sedghi Mohammad , Hakimi Ali , Nejatianfar Mahdi , Javaheri Tohid , Tavakoli Reza , Ahmadi Ramtin , Makarem Mansoureh , Azmi‐Naei Nazanin , Zahmatkesh Sangani Saeid , Kamandi Neda , Soleimanian AmirMohammad , Shavaleh Rasoul , Foogerdi Molood , Rahmani Kazem 
Published: November 2023

AbstractBackgroundThe significant role of red blood cell distribution width (RDW) and D‐Dimer as prognostic factors in patients with some blood malignancies has been reported recently.AimWe designed and performed a meta‐analysis to investigate the prognostic roles of RDW and D‐Dimer in subjects with diffuse large B‐cell lymphoma (DLBCL).Materials and MethodsWe systematically reviewed PubMed‐Medline, SCOPUS, EMBASE, Web of Science Core Collection, and Google Scholar up to the present to look for publications on prognostic effects of RDW and D‐Dimer in DLBCL patients. For investigation of the associations between RDW and D‐Dimer with the overall survival (OS) and progression‐free survival (PFS) of the DLBCL cases, hazard ratio (HR) with 95% confidence intervals (CIs) was used.ResultsWe included 13 eligible studies in the present meta‐analysis. The results of pooled analysis showed that increased levels of RDW was related to poor OS (HR = 2.01, 95% CI: 1.62–2.48, p value <.01, I2 = 0%) and poor PFS (HR = 1.52, 95% CI: 1.24–1.85, p value <.01, I2 = 16%) among the DLBCL patients. Similarly, a significant relationship was found between increased D‐Dimer and poor OS (HR = 2.30, 95% CI: 1.03–5.14, p value <.05, I2 = 95%) of the DLBCL patients as well. In addition, there was no significant heterogeneity in OS (p value H = 0.65) and PFS (p value H = 0.31) related to RDW among studies included in the meta‐analysis.ConclusionOur finding clearly confirmed that elevated RDW levels and D‐Dimer were associated with adverse OS and PFS in DLBCL.
Pharmacokinetics and Bioequivalence of Amlodipine Besylate Tablet in Healthy Chinese Volunteers Under Fasting and Fed Conditions
Authors: Tang Liyuan , Wang Yanrong , Chen Ran , He Yuanyuan , Liu Ying , Wang Na , Sun Xiaoyan , Song Jingya 
Published: November 2023

AbstractThe purpose of this study was to compare the blood concentration and pharmacokinetic (PK) parameters of 2 formulations under fasting and ed conditions in healthy Chinese volunteers and to evaluate whether the 2 preparations were bioequivalent. This trial screened 170 subjects. Thirteen subjects were assigned to the fasting trial and 18 subjects to the fed trial; 1 subject in the fed trial group was automatically withdrawn for personal reasons. Two cycles had a 14‐day washout period. This clinical study was a bioequivalence study, with PK parameters as end point indicators. The bioequivalence PK parameters were the maximal concentration (Cmax), area under the blood drug concentration‐time curve from 0 to 72 hours (AUC0‐72 h), and the time to peak plasma concentration (tmax) which were determined in human plasma by the liquid chromatography‐tandem mass spectrometry method, and nonatrioventricular model analysis was used to determine Cmax, AUC0‐72 h, tmax, and other PK parameters. The incidence of adverse events was calculated on the basis of System Organ Classification and Preferred Terms. The results showed that the amlodipine besylate tablets met the equivalence range requirements of bioequivalence in the guidelines for human bioavailability and bioequivalence testing under fasting and fed conditions, compared to the fasting test; the tmax of the fed test was almost unchanged; and the Cmax and AUC0‐72 h showed no difference between fasting and fed conditions. It was confirmed that both formulations were well tolerated, and no new safety signals were observed.
A lightweight hierarchical method for improving security in the internet of things using fuzzy logic
Authors: Doostani Shadi , Barati Hamid , Barati Ali 
Published: November 2023

SummaryThe internet of things (IoT) refers to the interconnection of various devices through the internet. With the help of IoT, different applications and devices can interact with each other and even with humans through the internet. However, the widespread use of IoT in homes, offices, and private companies has raised concerns about privacy and security. The theft of user information by hackers is a major challenge that has hindered the adoption of IoT. This paper proposes a method for improving security on two levels: intra‐cluster and inter‐cluster. In the intra‐cluster phase, the cluster head uses fuzzy logic to measure the trust level of nodes. If the node is trusted, the information is received and sent to the destination. In the inter‐cluster phase, data between cluster heads is encrypted using column transposition encryption. The encryption is hop by hop, and the encryption key is changed at each hop. The proposed method is simulated using NS‐2 software. A comparison of the proposed method's performance with conventional methods shows that the proposed method results in better packet delivery rate, throughput, and prevention of link spoofing attacks.
Chronological analysis of periodontal bone loss in experimental periodontitis in mice
Authors: Hernández Martínez Cristhiam de J.  , Felix Silva Pedro  , Salvador Sergio L. , Messora Michel , Palioto Daniela B. 
Published: November 2023

AbstractObjectivesPeriodontal disease is understood to be a result of dysbiotic interactions between the host and the biofilm, causing a unique reaction for each individual, which in turn characterizes their susceptibility. The objective of this study was to chronologically evaluate periodontal tissue destruction induced by systemic bacterial challenge in known susceptible (BALB/c) and resistant (C57BL/6) mouse lineages.Material and MethodsAnimals, 6–8 weeks old, were allocated into three experimental groups: Negative control (C), Gavage with sterile carboxymethyl cellulose 2%—without bacteria (Sham), and Gavage with carboxymethyl cellulose 2% + Porphyromonas gingivalis (Pg‐W83). Before infection, all animals received antibiotic treatment (sulfamethoxazole/trimethoprim, 400/80 mg/5 mL) for 7 days, followed by 3 days of rest. Microbial challenge was performed 3 times per week for 1, 2, or 3 weeks. After that, the animals were kept until the completion of 42 days of experiments, when they were euthanized. The alveolar bone microarchitecture was assessed by computed microtomography.ResultsBoth C57BL/6 and BALB/c mice exhibited significant bone volume loss and lower trabecular thickness as well as greater bone porosity compared to the (C) and (Sham) groups after 1 week of microbial challenge (p < .001). When comparing only the gavage groups regarding disease implantation, time and lineage, it was possible to observe that within 1 week of induction the disease was more established in BALB/c than in C57BL/6 (p < .05).ConclusionsOur results reflected that after 1 week of microbial challenge, there was evidence of alveolar bone loss for both lineages, with the loss observed in BALB/c mice being more pronounced.
Circular economy: On the road to ISO 59000 family of standards
Authors: Arana‐Landin German , Sigüenza Waleska , Landeta‐Manzano Beñat , Laskurain‐Iturbe Iker 
Published: November 2023

AbstractThe article aims to analyse the experience regarding the adoption of the voluntary French standard XP X30‐901, used as the main reference point to design the ISO 59004 that will define the terminology, principles and guidance to provide a common understanding of the circular economy. After an analysis of its structure, based on a case study conducted in a pioneering company, the study provides an innovative contribution to the understanding of the adoption of Circular Economy Project Management Systems by companies to move towards CE through XP X30‐901, explaining the main drivers and barriers, the standard's adoption process and the effects in the results. The main enabler is considered its experience working with an integrated management system. The adoption has helped to integrate actions to improve the indicators of the seven areas considered by the standard: Sustainable Sourcing, Eco‐design, Industrial Symbiosis, Functional Economy, Responsible Consumption, Extending Lifetime and Efficient Management of Materials at the end of life. Overall, the company appears to be satisfied with the adoption, mainly, because it has helped it to structure actions to improve its circularity indicators. However, the need for capital to develop the investments has been the most important barrier.
Blockchain and the transition to the circular economy: A literature review
Authors: Schmidt Jefferson Leandro , Sehnem Simone , Spuldaro Juliano Danilo 
Published: November 2023

AbstractCompanies and industries face various challenges when it comes to embracing the circular economy (CE). These challenges not only deter companies from adopting effective strategies that promote it but also hinder industries from effectively establishing a circular system that ensures the addition of economic value to the supply chain. To address these challenges, blockchain technology has emerged as a new and revolutionary protocol for sharing and updating information. It does so by linking databases within a decentralized, peer‐to‐peer, open‐access network, guaranteeing secure, immutable, and irreversible operations. Within this context, the primary objective of this article is to investigate how blockchain technology supports the transition to the CE. Additionally, the paper aims to identify the barriers that hinder the process of transitioning to the CE. To achieve this, a systematic literature review (SLR) was conducted, considering 22 articles published in recent years across Scopus, Web of Science, and Science Direct databases. The results of this review underscore the considerable potential of blockchain in supporting companies and industries as they embrace their roles in the CE and seek to overcome the barriers they encounter. The findings reveal that blockchain supports the transition to the CE by facilitating decentralization, enabling smart contracting, enhancing information sharing and improvement, ensuring traceability and transparency, providing incentives, offering protection and security, and promoting value creation. However, in examining the barriers that blockchain may face in supporting companies and industries as they transition to the CE, certain challenges are highlighted. These include issues related to low scalability, insufficient funding, underdeveloped regulations, limited infrastructure support, a lack of standardization and generalization, high initial adoption costs, associated risks, and a deficiency in engagement and awareness. In conclusion, this study contributes to the existing literature by demonstrating that although barriers may pose challenges to blockchain's role in facilitating the CE transition, the benefits it offers are likely to outweigh these obstacles.
Plasma SARS‐CoV‐2 RNA elimination and RAGE kinetics distinguish COVID‐19 severity
Authors: Deng Xiaoyan , Gantner Pierre , Forestell Julia , Pagliuzza Amélie , Brunet‐Ratnasingham Elsa , Durand Madeleine , Kaufmann Daniel E , Chomont Nicolas , Craig Morgan 
Published: November 2023

AbstractObjectivesIdentifying biomarkers causing differential SARS‐CoV‐2 infection kinetics associated with severe COVID‐19 is fundamental for effective diagnostics and therapeutic planning.MethodsIn this work, we applied mathematical modelling to investigate the relationships between patient characteristics, plasma SARS‐CoV‐2 RNA dynamics and COVID‐19 severity. Using a straightforward mathematical model of within‐host viral kinetics, we estimated key model parameters from serial plasma viral RNA (vRNA) samples from 256 hospitalised COVID‐19+ patients.ResultsOur model predicted that clearance rates distinguish key differences in plasma vRNA kinetics and severe COVID‐19. Moreover, our analyses revealed a strong correlation between plasma vRNA kinetics and plasma receptor for advanced glycation end products (RAGE) concentrations (a plasma biomarker of lung damage), collected in parallel to plasma vRNA from patients in our cohort, suggesting that RAGE can substitute for viral plasma shedding dynamics to prospectively classify seriously ill patients.ConclusionOverall, our study identifies factors of COVID‐19 severity, supports interventions to accelerate viral clearance and underlines the importance of mathematical modelling to better understand COVID‐19.
Improving thymus implantation for congenital athymia with interleukin‐7
Authors: Min Hyunjung , Valente Laura A , Xu Li , O'Neil Shane M , Begg Lauren R , Kurtzberg Joanne , Filiano Anthony J 
Published: November 2023

AbstractObjectivesThymus implantation is a recently FDA‐approved therapy for congenital athymia. Patients receiving thymus implantation develop a functional but incomplete T cell compartment. Our objective was to develop a mouse model to study clinical thymus implantation in congenital athymia and to optimise implantation procedures to maximise T cell education and expansion of naïve T cells.MethodsUsing Foxn1nu athymic mice as recipients, we tested MHC‐matched and ‐mismatched donor thymi that were implanted as fresh tissue or cultured to remove donor T cells. We first implanted thymus under the kidney capsule and then optimised intramuscular implantation. Using competitive adoptive transfer assays, we investigated whether the failure of newly developed T cells to expand into a complete T cell compartment was because of intrinsic deficits or whether there were deficits in engaging MHC molecules in the periphery. Finally, we tested whether recombinant IL‐7 would promote the expansion of host naïve T cells educated by the implanted thymus.ResultsWe determined that thymus implants in Foxn1nu athymic mice mimic many aspects of clinical thymus implants in patients with congenital athymia. When we implanted cultured, MHC‐mismatched donor thymus into Foxn1nu athymic mice, mice developed a limited T cell compartment with notably underdeveloped naïve populations and overrepresented memory‐like T cells. Newly generated T cells were predominantly educated by MHC molecules expressed by the donor thymus, thus potentially undergoing another round of selection once in the peripheral circulation. Using competitive adoptive transfer assays, we compared expansion rates of T cells educated on donor thymus versus T cells educated during typical thymopoiesis in MHC‐matched and ‐mismatched environments. Once in the circulation, regardless of the MHC haplotypes, T cells educated on a donor thymus underwent abnormal expansion with initially more robust proliferation coupled with greater cell death, resembling IL‐7 independent spontaneous expansion. Treating implanted mice with recombinant interleukin (IL‐7) promoted homeostatic expansion that improved T cell development, expanded the T cell receptor repertoire, and normalised the naïve T cell compartment.ConclusionWe conclude that implanting cultured thymus into the muscle of Foxn1nu athymic mice is an appropriate system to study thymus implantation for congenital athymia and immunodeficiencies. T cells are educated by the donor thymus, yet naïve T cells have deficits in expansion. IL‐7 greatly improves T cell development after thymus implantation and may offer a novel strategy to improve outcomes of clinical thymus implantation.
Metformin reduces hepatocarcinogenesis by inducing downregulation of Cyp26a1 and CD8+ T cells
Authors: He Weizhi , Wang Xicheng , Chen Miaomiao , Li Chong , Chen Wenjian , Pan Lili , Cui Yangyang , Yu Zhao , Wu Guoxiu , Yang Yang , Xu Mingyang , Dong Zhaoxuan , Ma Keming , Wang Jinghan , He Zhiying 
Published: November 2023

AbstractBackgroundHepatocellular carcinoma (HCC) is a highly heterogeneous cancer with major challenges in both prevention and therapy. Metformin, adenosine monophosphate‐activated protein kinase (AMPK) activator, has been suggested to reduce the incidence of HCC when used for patients with diabetes in preclinical and clinical studies. However, the possible effects of metformin and their mechanisms of action in non‐diabetic HCC have not been adequately investigated.MethodsFah−/− mice were used to construct a liver‐injury‐induced non‐diabetic HCC model for exploring hepatocarcinogenesis and therapeutic potential of metformin. Changes in relevant tumour and biochemical indicators were measured. Bulk and single‐cell RNA‐sequencing analyses were performed to validate the crucial role of proinflammatory/pro‐tumour CD8+ T cells. In vitro and in vivo experiments were performed to confirm Cyp26a1‐related antitumour mechanisms of metformin.ResultsRNA‐sequencing analysis showed that chronic liver injury led to significant changes in AMPK‐, glucose‐ and retinol metabolism‐related pathways in Fah−/− mice. Metformin prevented the formation of non‐diabetic HCC in Fah−/− mice with chronic liver injury. Cyp26a1 ddexpression in hepatocytes was significantly suppressed after metformin treatment. Moreover, downregulation of Cyp26a1 occurred in conjunction with increased levels of all‐trans‐retinoic acid (atRA), which is involved in the activation of metformin‐suppressed hepatocarcinogenesis in Fah−/− mice. In contrast, both CD8+ T‐cell infiltration and proinflammatory/pro‐tumour cytokines in the liver were significantly upregulated in Fah−/− mice during chronic liver injury, which was notably reversed by either metformin or atRA treatment. Regarding mechanisms, metformin regulated the decrease in Cyp26a1 enzyme expression and increased atRA expression via the AMPK/STAT3/Gadd45β/JNK/c‐Jun pathway.ConclusionsMetformin inhibits non‐diabetic HCC by upregulating atRA levels and downregulating CD8+ T cells. This is the first reporting that the traditional drug metformin regulates the metabolite atRA via the Cyp26a1‐involved pathway. The present study provides a potential application of metformin and atRA in non‐diabetic HCC.