bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unearthed opium: development of a UHPLC-MS/MS method for the determination of Papaver somniferum alkaloids in Daunian vessels
Authors: Vincenti Flaminia , Montesano Camilla , Ciccola Alessandro , Serafini Ilaria , Favero Gabriele , Pallotta Matteo , Pagano Flavia , Di Francesco Gaia , Croce Martina , Leone Maria Laura , Muntoni Italo Maria , Sergi Manuel 
Published: July 2023

Introduction: The analysis of organic residue in ancient vessels to investigate early-age civilization habits is an important archeological application that needs advanced analytical methods. However, these procedures should meet inherent requisites such as low sampling invasiveness and high sensitivity for trace analysis. This study deals with the development of advanced analytical methods for the detection of opium alkaloids in ceramic vessels and its first application to the study of Daunian pots dating back to the VIII–IV sec BC.Methods: All the stages of the analytical procedure, from sampling to analysis, were carefully optimized. Concerning sampling, the traditional scraping approach was compared with a swabbing strategy which permitted minimizing sample encroachment. Extraction was based on pressurized liquid extraction or ultrasound-assisted liquid extraction, followed by dispersive liquid–liquid microextraction, which allowed concentration enrichment. On the other hand, a UHPLC-MS/MS method was specifically developed and validated to obtain reliable data. Some Daunian pots, belonging to the Ceci-Macrini private archeological collection, were selected for sample withdrawal as their iconography could suggest opium usage.Results: Several of the analyzed samples resulted positive to thebaine and less frequently to morphine and codeine; furthermore, 70% of the analyzed items tested positive for at least one opium alkaloid. Positive findings were common to all the samples collected in the pots, suggesting that scraping and swabbing provided comparable results and validating this unusual sampling strategy. All samples were additionally analyzed by UHPLC-HRMS to further improve the confidence level of the identified compounds. The obtained results shed new light on the hypothesis of opium usage by the ancient Daunian civilization. Furthermore, this study provided suitable analytical tools for further investigations on the same topic, with a good level of confidence in the quality of the results.
Establishment of a mathematical prediction model for voriconazole stable maintenance dose: a prospective study
Authors: Zhou Lijuan , Li Min , Li Huihong , Guo Zhiqiang , Gao Yanqiu , Zhang Hua , Qin Fuli , Sang Zhihui , Xing Qinghe , Cheng Long , Cao Wei 
Published: July 2023

BackgroundIn patients with invasive fungal infection (IFI), the steady-state serum trough concentration (Cmin) of voriconazole (VCZ) is highly variable and can lead to treatment failure (Cmin &lt; 0.5 mg/L) and toxicity (Cmin ≥ 5.0 mg/L). However, It remains challenging to determine the ideal maintenance dose to achieve the desired Cmin level quickly.AimsThis randomized, prospective observational single-center study aimed to identify factors affecting VCZ-Cmin and maintenance dose and create an algorithmic model to predict the necessary maintenance dose. MeThe study enrolled 306 adult IFI patients, split into two groups: non-gene-directed (A) (where CYP2C19 phenotype is not involved in determining VCZ dose) and gene-directed (B) (where CYP2C19 phenotype is involved in determining VCZ dose).ResultsResults indicated that CYP2C19 genetic polymorphisms might significantly impact VCZ loading and maintenance dose selection. CYP2C19 phenotype, C-reaction protein (CRP), and average daily dose/body weight were significant influencers on VCZ-Cmin, while CYP2C19 phenotype, CRP, and body weight significantly impacted VCZ maintenance dose. A feasible predictive formula for VCZ stable maintenance dose was derived from the regression equation as a maintenance dose (mg) =282.774-0.735×age (year)+2.946×body weight(Kg)-19.402×CYP2C19 phenotype (UM/RM/NM:0, IM:1, PM:2)-0.316×CRP (mg/L) (p &lt; 0.001).DiscussionDiThis formula may serve as a valuable supplement to the Clinical Pharmacogenetics Implementation Consortium (CPIC®) guideline for CYP2C19 and VCZ therapy, especially for IFI patients with highly variable inflammatory cytokines during VCZ therapy.
Regulation of FGF2-induced proliferation by inhibitory GPCR in normal pituitary cells
Authors: Sosa Liliana del V. , Picech Florencia , Perez Pablo , Gutierrez Silvina , Leal Rodrigo Bainy , De Paul Ana , Torres Alicia , Petiti Juan Pablo 
Published: July 2023

IntroductionIntracellular communication is essential for the maintenance of the anterior pituitary gland plasticity. The aim of this study was to evaluate whether GPCR-Gαi modulates basic fibroblast growth factor (FGF2)-induced proliferative activity in normal pituitary cell populations.MethodsAnterior pituitary primary cell cultures from Wistar female rats were treated with FGF2 (10ng/mL) or somatostatin analog (SSTa, 100nM) alone or co-incubated with or without the inhibitors of GPCR-Gαi, pertussis toxin (PTX, 500nM), MEK inhibitor (U0126, 100µM) or PI3K inhibitor (LY 294002, 10 μM).ResultsFGF2 increased and SSTa decreased the lactotroph and somatotroph BrdU uptak2e (p&lt;0.05) whereas the FGF2-induced S-phase entry was prevented by SSTa co-incubation in both cell types, with these effects being reverted by PTX, U0126 or LY294002 pre-incubation. The inhibition of lactotroph and somatotroph mitosis was associated with a downregulation of c-Jun expression, a decrease of phosphorylated (p) ERK and pAKT. Furthermore, SSTa was observed to inhibit the S-phase entry induced by FGF2, resulting in a further increase in the number of cells in the G1 phase and a concomitant reduction in the number of cells in the S phases (p&lt; 0.05), effects related to a decrease of cyclin D1 expression and an increase in the expression of the cell cycle inhibitors p27 and p21.DiscussionIn summary, the GPCR-Gαi activated by SSTa blocked the pro-proliferative effect of FGF2 in normal pituitary cells via a MEK-dependent mechanism, which acts as a mediator of both anti and pro-mitogenic signals, that may regulate the principal effectors of the G1 to S-phase transition.
T-lymphocytes from focused ultrasound ablation subsequently mediate cellular antitumor immunity after adoptive cell transfer immunotherapy
Authors: Ran Li-Feng , Xie Xun-Peng , Xia Ji-Zhu , Xie Fang-Lin , Fan Yan-Min , Wu Feng 
Published: July 2023

BackgroundOur previous studies found that high-intensity focused ultrasound (HIFU) stimulated tumor-specific T cells in a mouse H22 tumor model, and adoptive transfer of the T cells from HIFU-treated mice could subsequently elicit stronger inhibition on the growth and progression of the implanted tumors. The aim of this study was to investigate the mechanism of T cells from focused ultrasound ablation in HIFU-mediated immunomodulation.MethodsSixty H22 tumor-bearing mice were treated by either HIFU or sham-HIFU, and 30 naïve syngeneic mice served as controls. All mice were euthanized on day 14 after HIFU and splenic T cell suspensions were obtained in each group. Using an adoptive cell transfer model, a total of 1 × 106 T cells from HIFU treated-mice were intravenously injected into each syngeneic H22 tumor-bearing mouse twice on day 3 and 4, followed by the sacrifice for immunological assessments at 14 days after the adoptive transfer.ResultsT cells from HIFU-treated mice could significantly enhance the cytotoxicity of CTLs (p &lt; 0.001), with a significant increase of TNF-α (p &lt; 0.001) and IFN-γ secretion (p &lt; 0.001). Compared to control and sham-HIFU groups, the number of Fas ligand+ and perforin+ tumor-infiltrating lymphocytes (TILs) and apoptotic H22 tumor cells were significantly higher (p &lt; 0.001) in the HIFU group. There were linear correlations between apoptotic tumor cells and Fas ligand+ TILs (r = 0.9145, p &lt; 0.001) and perforin+ TILs (r = 0.9619, p &lt; 0.001).ConclusionT cells from HIFU-treated mice can subsequently mediate cellular antitumor immunity, which may play an important role in the HIFU-based immunomodulation.
Exploring the contribution of pro-inflammatory cytokines to impaired wound healing in diabetes
Authors: Nirenjen S. , Narayanan J. , Tamilanban T. , Subramaniyan Vetriselvan , Chitra V. , Fuloria Neeraj Kumar , Wong Ling Shing , Ramachawolran Gobinath , Sekar Mahendran , Gupta Gaurav , Fuloria Shivkanya , Chinni Suresh V. , Selvaraj Siddharthan 
Published: July 2023

BackgroundImpaired wound healing is the most common and significant complication of Diabetes. While most other complications of Diabetes have better treatment options, diabetic wounds remain a burden as they can cause pain and suffering in patients. Wound closure and repair are orchestrated by a sequence of events aided by the release of pro-inflammatory cytokines, which are dysregulated in cases of Diabetes, making the wound environment unfavorable for healing and delaying the wound healing processes. This concise review provides an overview of the dysregulation of pro-inflammatory cytokines and offers insights into better therapeutic outcomes.Purpose of reviewAlthough many therapeutic approaches have been lined up nowadays to treat Diabetes, there are no proper treatment modalities proposed yet in treating diabetic wounds due to the lack of understanding about the role of inflammatory mediators, especially Pro-inflammatory mediators- Cytokines, in the process of Wound healing which we mainly focus on this review.Recent findingsAlthough complications of Diabetes mellitus are most reported after years of diagnosis, the most severe critical complication is impaired Wound Healing among Diabetes patients. Even though Trauma, Peripheral Artery Disease, and Peripheral Neuropathy are the leading triggering factors for the development of ulcerations, the most significant issue contributing to the development of complicated cutaneous wounds is wound healing impairment. It may even end up with amputation. Newer therapeutic approaches such as incorporating the additives in the present dressing materials, which include antimicrobial molecules and immunomodulatory cytokines is of better therapeutic value.SummaryThe adoption of these technologies and the establishment of novel therapeutic interventions is difficult since there is a gap in terms of a complete understanding of the pathophysiological mechanisms at the cellular and molecular level and the lack of data in terms of the assessment of safety and bioavailability differences in the individuals’ patients. The target-specific pro-inflammatory cytokines-based therapies, either by upregulation or downregulation of them, will be helpful in the wound healing process and thereby enhances the Quality of life in patients, which is the goal of drug therapy.
Swiss Survey on current practices and opinions on clinical constellations triggering the search for PNH clones
Authors: Rovó Alicia , Gavillet Mathilde , Drexler Beatrice , Keller Peter , Schneider Jenny Sarah , Colucci Giuseppe , Beauverd Yan , Dorland Hendrika Anette van , Pollak Matthias , Schmidt Adrian , De Gottardi Andrea , Bissig Marina , Lehmann Thomas , Duchosal Michel A. , Zeerleder Sacha 
Published: July 2023

This national survey investigated the current practice in Switzerland by collecting participants' opinions on paroxysmal nocturnal hemoglobinuria (PNH) clone assessment and clinical practice.AimThis study aimed to investigate clinical indications prompting PNH clones' assessment and physician's accessibility of a flow cytometry facility, and also to understand clinical attitudes on the follow-up (FU) of patients with PNH clones.MethodsThe survey includes 16 multiple-choice questions related to PNH and targets physicians with a definite level of experience in the topic using two screener questions. Opinion on clinical management was collected using hypothetical clinical situations. Each participant had the option of being contacted to further discuss the survey results. This was an online survey, and 264 physicians were contacted through email once a week for 5 weeks from September 2020.ResultsIn total, 64 physicians (24.2%) from 23 institutions participated (81.3% hematologists and 67.2% from university hospitals). All had access to flow cytometry for PNH clone testing, with 76.6% having access within their own institution. The main reasons to assess for PNH clones were unexplained thrombosis and/or hemolysis, and/or aplastic anemia (AA). Patients in FU for PNH clones were more likely to be aplastic anemia (AA) and symptomatic PNH. In total, 61% of the participants investigated PNH clones repetitively during FU in AA/myelodysplastic syndromes patients, even when there was no PNH clone found at diagnosis, and 75% of the participants tested at least once a year during FU. Opinions related to clinical management were scattered.ConclusionThe need to adhere to guidelines for the assessment, interpretation, and reporting of PNH clones emerges as the most important finding, as well as consensus for the management of less well-defined clinical situations. Even though there are several international guidelines, clear information addressing specific topics such as the type of anticoagulant to use and its duration, as well as the indication for treatment with complement inhibitors in some borderline situations are needed. The analysis and the discussion of this survey provide the basis for understanding the unmet needs of PNH clone assessment and clinical practice in Switzerland.
Primary renal myxoid liposarcoma with pancreatic invasion on 18F-FDG PET/CT: first case report and literature review
Authors: Huang Wenpeng , Chao Fangfang , Zhang Yongbai , Li Liming , Gao Yuan , Qiu Yongkang , Gao Jianbo , Kang Lei 
Published: July 2023

BackgroundMyxoid liposarcoma (MLS) is a rare malignant soft tissue sarcoma that predominantly manifests in the deep soft tissues of the extremities, particularly within the musculature of the thigh. Unlike other types of liposarcoma, MLS demonstrates a propensity for metastasis to atypical sites, including the lung parenchyma, soft tissues, retroperitoneum, mediastinum, breast, liver, thymus, lymph nodes, and bones. The definitive diagnosis primarily relies on histology with HE staining. Imaging modalities such as ultrasound, CT, MRI, and 18F-FDG PET/CT scans serve as valuable tools for tumor identification.Case reportA 57-year-old man presented with symptoms of abdominal distention and vomiting 1 month ago. Contrast-enhancement CT revealed a heterogeneous hypodense mass in the upper-middle part of the left kidney, displaying irregular morphology and protrusion towards the exterior of the kidney, with abundant blood supply and had a maximum dimension of approximately 10.7 cm × 9.0 cm. Additionally, a rounded soft tissue density was identified in the pancreatic body. Multiplanar reconstruction demonstrated a connection between the pancreatic lesion and the kidney mass. 18F-FDG PET/CT was conducted for staging, revealing significant growth of the lesion in the upper-middle part of the left kidney, extending beyond the kidney and infiltrating the pancreatic body. The lesion demonstrated remarkably high 18F-FDG uptake (SUVmax = 10.2, MTV = 136.13 cm3, TLG = 484.62). The postoperative pathological examination confirmed the diagnosis of MLS. On the 10th day post-surgery, the patient presented with tumor recurrence and underwent another surgical resection. Unfortunately, during the operation, the patient experienced a sudden cardiac arrest and died.ConclusionRenal MLS with invasion into the pancreas is very rare in clinical practice. Due to the limited research on the utilization of 18F-FDG PET/CT in this particular context, given the rarity and low incidence of MLS, its role remains largely unexplored. As PET/CT imaging becomes increasingly prevalent, thorough imaging of disease sites becomes indispensable for the development of treatment protocols and the monitoring of treatment response.
Dynamic distribution of Massilia spp. in sewage, substrate, plant rhizosphere/phyllosphere and air of constructed wetland ecosystem
Authors: Xu Ailing , Liu Congcong , Zhao Shuke , Song Zhiwen , Sun Hui 
Published: July 2023

IntroductionMassilia bacteria are widely distributed and have various ecological functions. Preliminary studies have shown that Massilia is the dominant species in constructed wetland ecosystems, but its species composition and distribution in constructed wetlands are still unclear.MethodsIn this paper, the in-house-designed primers were used to construct a 16S rDNA clone library of Massilia. The RFLP sequence analysis method was used to analyze the diversity of Massilia clone library and the composition of Massilia in sewage, substrate, plant rhizosphere, plant phyllosphere and air in a constructed wetland sewage treatment system. Redundancy analysis (RDA) and canonical correspondence analysis (CCA) were used to analyze the correlation between environmental factors and the population characteristics of Massilia in the corresponding environment. The dominant species of Massilia were analyzed for differences.ResultsThe results showed that the 16S rDNA clone library in primer 5 worked well. According to the clone library diversity index analysis, the richness of Massilia varied significantly in different environments in different seasons, where the overall summer and autumn richness was higher than that in the spring and winter. The relative abundance of 5 Massilia in the constructed wetland ecosystem was greater than 1% in all samples, which were M. alkalitolerans, M. albidiflava, M. aurea, M. brevitalea, and M. timonae. The seasonal variation of dominant genera was significantly correlated with environmental factors in constructed wetlands.DiscussionThe above results indicated that the species of Massilia were abundant and widely distributed in the constructed wetland ecosystem, and there were significant seasonal differences. In addition, the Massilia clone library of constructed wetland was constructed for the first time in this study and the valuable data of Massilia community structure were provided, which was conducive to the further study of microbial community in constructed wetland.
Postmortem skin microbiome signatures associated with human cadavers within the first 12 h at the morgue
Authors: Iancu Lavinia , Muslim Azdayanti , Aazmi Shafiq , Jitaru Victor 
Published: July 2023

IntroductionForensic microbiome studies expanded during the last decade, aiming to identify putative bacterial biomarkers to be used for the postmortem interval (PMI) estimation. Bacterial diversity and dynamics during decomposition are influenced by each individual’s micro and macroenvironment, ante and postmortem conditions, varying across body sites and time. The skin, the largest organ of the human body, hosts a diverse microbial diversity, representing the first line of defense of a living individual. Targeting the investigation of the postmortem skin microbiome could help understanding the role of microbes during decomposition, and association with the ante and postmortem conditions.MethodsThe current study aimed to identify the postmortem skin microbiome signatures associated with eight human bodies, received at the Institute of Legal Medicine Iasi, Romania, during April and May 2021. A total of 162 samples (including triplicate) representing face and hands skin microbiome were investigated via Illumina MiSeq, upon arrival at the morgue (T0) and after 12 hours (T1).ResultsThe taxonomic characteristics of the skin microbiota varied across different body sites. However, there were no significant differences in taxonomic profiles between collection time, T0 and T1, except for some dynamic changes in the abundance of dominant bacteria. Moreover, different microbial signatures have been associated with a specific cause of death, such as cardiovascular disease, while an elevated blood alcohol level could be associated with a decrease in bacterial richness and diversity.DiscussionThe places where the bodies were discovered seemed to play an important role in explaining the bacterial diversity composition. This study shows promising results towards finding common postmortem bacterial signatures associated with human cadavers within the first 12h at the morgue.
Changes in plasma endocannabinoids concentrations correlate with 18F-FDG PET/MR uptake in brown adipocytes in humans
Authors: Maliszewska Katarzyna , Miniewska Katarzyna , Godlewski Adrian , Gosk Wioleta , Mojsak Malgorzata , Kretowski Adam , Ciborowski Michal 
Published: July 2023

Introduction: Recent data suggest a possible role of endocannabinoids in the regulation of brown adipose tissue (BAT) activity. Those findings indicate potential treatment options for obesity. The aim of this study was to evaluate the relationship between plasma endocannabinoids concentrations and the presence of BAT in humans.Methods: The study group consisted of 25 subjects divided into two groups: BAT positive BAT(+), (n = 17, median age = 25 years) and BAT negative BAT(−), (n = 8, median age = 28 years). BAT was estimated using 18F-FDG PET/MR after 2 h of cold exposure. The level of plasma endocannabinoids was assessed at baseline, 60 min and 120 min of cold exposure.Results: In both groups, BAT(+) and BAT(−), during the cooling, we observed a decrease of the same endocannabinoids: arachidonoylethanolamide (AEA), eicosapentaenoyl ethanolamide (EPEA) and oleoyl ethanolamide (OEA) with a much more profound decline in BAT(+) subjects. Statistically significant fall of PEA (palmitoylethanolamide) and SEA (stearoylethanolamide) concentrations after 60 min (FC = 0.7, p = 0.007 and FC = 0.8, p = 0.03, respectively) and 120 min (FC = 0.81, p = 0.004, and FC = 0.9, p = 0.01, respectively) of cooling was observed only in individuals with BAT.Conclusion: We noticed the profound decline of endocannabinoids concentrations in subjects with increased 18F-FDG PET/MR uptake in BAT. Identification of a new molecules related to BAT activity may create a new target for obesity treatment.