bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urbanization causes shifts in the functional traits and foraging activity, and alters food particle size preference and biomass removal of urban-dwelling ants
Authors: Chen Yuan-Hung , Neoh Kok-Boon 
Published: July 2023

Urbanization may lead to changes in assemblage and result in shifts in trait distribution from natural habitats to highly urbanized habitats. The shift in functional traits can affect ecosystem functions in urban areas. This study explored the foraging period of ants over 72 h and determined the relationship between the behavioral, morphological, and physiological traits of local foragers ants and environmental conditions in urban and forest sites. In addition, this study examined the ants’ ecosystem functions and compared it with that of their forest counterparts. Our results revealed that the foraging period of ants (i.e., Cardiocondyla sp.1, Monomorium chinense, Paratrechina longicornis, Pheidole megacephala, and Solenopsis sp.1) in urban areas peaked between 0900 and 1500 and that of some ants (i.e., Carebara diversa, P. megacephala, Pheidole fervens, Plagiolepis longwang, and Nylanderia sp.1) in forest areas was constant over time. For urban ants, a weak correlation was observed between foraging period and body size traits (i.e., Weber’s length and head width). This finding indicates that the major factor underlying the change in the foraging period might not be related to body size. Rather, the change may be attributed to synchronization between food availability and human activity (waste disposal; i.e., between 0900 and 1800). The shift in the functional traits of ants affects ecosystem functions in urban areas. In urban areas, although only one predatory ant species (P. megacephala) was sampled, its activity density was high. Most of these individuals were active during the daytime, indicating that the predatory behavior of ants in the novel urban environment has decreased temporally and is limited to the daytime. Urban ants tended to choose smaller food particles, whereas forest ants preferred larger food particles and had a twofold higher food removal rate.
Persistent and transient olfactory deficits in COVID-19 are associated to inflammation and zinc homeostasis
Authors: Lupi Lorenzo , Bordin Anna , Sales Gabriele , Colaianni Davide , Vitiello Adriana , Biscontin Alberto , Reale Alberto , Garzino-Demo Alfredo , Antonini Angelo , Ottaviano Giancarlo , Mucignat Carla , Parolin Cristina , Calistri Arianna , De Pittà Cristiano 
Published: July 2023

IntroductionThe Coronavirus Disease 2019 (COVID-19) is mainly a respiratory syndrome that can affect multiple organ systems, causing a variety of symptoms. Among the most common and characteristic symptoms are deficits in smell and taste perception, which may last for weeks/months after COVID-19 diagnosis owing to mechanisms that are not fully elucidated.MethodsIn order to identify the determinants of olfactory symptom persistence, we obtained olfactory mucosa (OM) from 21 subjects, grouped according to clinical criteria: i) with persistent olfactory symptoms; ii) with transient olfactory symptoms; iii) without olfactory symptoms; and iv) non-COVID-19 controls. Cells from the olfactory mucosa were harvested for transcriptome analyses.Results and discussionRNA-Seq assays showed that gene expression levels are altered for a long time after infection. The expression profile of micro RNAs appeared significantly altered after infection, but no relationship with olfactory symptoms was found. On the other hand, patients with persistent olfactory deficits displayed increased levels of expression of genes involved in the inflammatory response and zinc homeostasis, suggesting an association with persistent or transient olfactory deficits in individuals who experienced SARS-CoV-2 infection.
Crosstalk between ferroptosis and chondrocytes in osteoarthritis: a systematic review of in vivo and in vitro studies
Authors: Cao Siyang , Wei Yihao , Xu Huihui , Weng Jian , Qi Tiantian , Yu Fei , Liu Su , Xiong Ao , Liu Peng , Zeng Hui 
Published: July 2023

PurposeRecent scientific reports have revealed a close association between ferroptosis and the occurrence and development of osteoarthritis (OA). Nevertheless, the precise mechanisms by which ferroptosis influences OA and how to hobble OA progression by inhibiting chondrocyte ferroptosis have not yet been fully elucidated. This study aims to conduct a comprehensive systematic review (SR) to address these gaps.MethodsFollowing the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020, we conducted a comprehensive search of the Embase, Ovid, ProQuest, PubMed, Scopus, the Cochrane Library, and Web of Science databases to identify relevant studies that investigate the association between ferroptosis and chondrocytes in OA. Our search included studies published from the inception of these databases until January 31st, 2023. Only studies that met the predetermined quality criteria were included in this SR.ResultsIn this comprehensive SR, a total of 21 studies that met the specified criteria were considered suitable and included in the current updated synthesis. The mechanisms underlying chondrocyte ferroptosis and its association with OA progression involve various biological phenomena, including mitochondrial dysfunction, dysregulated iron metabolism, oxidative stress, and crucial signaling pathways.ConclusionFerroptosis in chondrocytes has opened an entirely new chapter for the investigation of OA, and targeted regulation of it is springing up as an attractive and promising therapeutic tactic for OA.Systematic review registrationhttps://inplasy.com/inplasy-2023-3-0044/, identifier INPLASY202330044.
Development and validation of prognostic risk prediction models for hepatocellular carcinoma patients treated with immune checkpoint inhibitors based on a systematic review and meta-analysis of 47 cohorts
Authors: Ma Delin , Liu Mingkun , Zhai Xiangyu , Li Xianzhi , Jin Bin , Liu Yang 
Published: July 2023

ObjectiveTo identify the risk factors associated with prognosis in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICI) via meta-analysis. And to construct prediction models to aid in the prediction and improvement of prognosis.MethodsWe searched PubMed, Embase, Web of Science and Cochrane Library for relevant studies from inception to March 29, 2023. After completing literature screening and data extraction, we performed meta-analysis, sensitivity analysis, and subgroup analysis to identify risk factors associated with OS and PFS. Using the pooled hazard ratio value for each risk factor, we constructed prediction models, which were then validated using datasets from 19 centers in Japan and two centers in China, comprising a total of 204 patients.ResultsA total of 47 studies, involving a total of 7649 ICI-treated HCC patients, were included in the meta-analysis. After analyzing 18 risk factors, we identified AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number, vascular invasion and combination therapy as predictors for OS prediction model, while AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number and vascular invasion were selected as predictors for PFS model. To validate the models, we scored two independent cohorts of patients using both prediction models. Our models demonstrated good performance in these cohorts. In addition, in the pooled cohort of 204 patients, Our models also showed good performance with area under the curve (AUC) values of 0.712, 0.753, and 0.822 for the OS prediction model at 1-year, 2-year, and 3-year follow-up points, respectively, and AUC values of 0.575, 0.749 and 0.691 for the PFS prediction model Additionally, the calibration curve, decision curve analysis, and Kaplan-Meier curves in the pooled cohort all supported the validity of both models.ConclusionBased on the meta-analysis, we successfully constructed the OS and PFS prediction models for ICI-treated HCC patients. We also validated the models externally and observed good discrimination and calibration. The model’s selected indicators are easily obtainable, making them suitable for further application in clinical practice.
Antigen-specific cytokine profiles for pulmonary Mycobacterium avium complex disease stage diagnosis
Authors: Yamashita Yoshiro , Yasuda Ikkoh , Tanaka Takeshi , Ikeda Toru , Terada Mayumi , Takaki Masahiro , Tsuchihashi Yoshiko , Asoh Norichika , Ohara Yukiko , Enany Shymaa , Kobayashi Haruka , Matsumoto Sohkichi , Morimoto Konosuke 
Published: July 2023

IntroductionControlling pulmonary Mycobacterium avium complex (MAC) disease is difficult because there is no way to know the clinical stage accurately. There have been few attempts to use cell-mediated immunity for diagnosing the stage. The objective of this study was to characterize cytokine profiles of CD4+T and CD19+B cells that recognize various Mycobacterium avium-associated antigens in different clinical stages of MAC.MethodsA total of 47 MAC patients at different stages based on clinical information (14 before-treatment, 16 on-treatment, and 17 after-treatment) and 17 healthy controls were recruited. Peripheral blood mononuclear cells were cultured with specific antigens (MAV0968, 1160, 1276, and 4925), and the cytokine profiles (IFN-γ, TNF-α, IL-2, IL-10, IL-13, and IL-17) of CD4+/CD3+ and CD19+ cells were analyzed by flow cytometry.ResultsThe response of Th1 cytokines such as IFN-γ and TNF-α against various antigens was significantly higher in both the on-treatment and after-treatment groups than in the before-treatment group and control (P &lt; 0.01–0.0001 and P &lt; 0.05–0.0001). An analysis of polyfunctional T cells suggested that the presence of IL-2 is closely related to the stage after the start of treatment (P = 0.0309-P &lt; 0.0001) and is involved in memory function. Non-Th1 cytokines, such as IL-10 and IL-17, showed significantly higher responses in the before-treatment group (P &lt; 0.0001 and P &lt; 0.01–0.0001). These responses were not observed with purified protein derivative (PPD). CD19+B cells showed a response similar to that of CD4+T cells.ConclusionThere is a characteristic cytokine profile at each clinical stage of MAC.
Case Report: Intervention of radiotherapy improves the prognosis of rectal squamous cell carcinoma with high PD-L1 expression and enable patients to obtain NED status
Authors: Qu Fuyin , Xiao Linlin , Xiao Yuting , Gao Chao , Wang Xuan , Wang Yi , Gao Yuanhang , Wu Fengpeng , Liu Ming 
Published: July 2023

BackgroundRectal squamous cell carcinoma (RSCC) is a rare malignancy of the rectal tumor. Due to its extremely low incidence, there is still a lack of high-level treatment evidence and clinical consensus on this disease.Case reportIn this article, we report a treatment process of RSCC with high PD-L1 expression. Firstly, this patient received 2 cycles of Pembrolizumab immunotherapy, but the efficacy was less sanguine. Subsequently, 4 cycles of mFOLFOX6 chemotherapy were synchronously performed on the basis of the initial regimen. Although partial remission was achieved in the lymph nodes thereafter, the changes in the primary lesions were still not significant. After that, the patient received radiotherapy, and followed by 6 cycles of PC (Albumin-binding Paclitaxel and Nedaplatin) regimen chemotherapy combined with Pembrolizumab. Eventually, the patient achieved no evidence of disease (NED) status, and no signs of recurrence or metastasis were found after 12 months of follow-up.ConclusionThis is the first report of a RSCC patient with high PD-L1 expression achieving a complete response. Looking back over the whole treatment process of this patient, we found that the participation of radiotherapy was the inflection point of prominent efficacy, which may provide a new idea for the selection of comprehensive treatment strategies for patients with RSCC.
Target therapy for high-risk neuroblastoma treatment: integration of regulatory and scientific tools is needed
Authors: Ceci Adriana , Conte Rosa , Didio Antonella , Landi Annalisa , Ruggieri Lucia , Giannuzzi Viviana , Bonifazi Fedele 
Published: July 2023

IntroductionSeveral new active substances (ASs) targeting neuroblastoma (NBL) are under study. We aim to describe the developmental and regulatory status of a sample of ASs targeting NBL to underline the existing regulatory gaps in product development and to discuss possible improvements.MethodsThe developmental and regulatory statuses of the identified ASs targeting NBL were investigated by searching for preclinical studies, clinical trials (CTs), marketing authorizations, pediatric investigation plans (PIPs), waivers, orphan designations, and other regulatory procedures.ResultsA total of 188 ASs were identified. Of these, 55 were considered ‘not under development' without preclinical or clinical studies. Preclinical studies were found for 115 ASs, of which 54 were associated with a medicinal product. A total of 283 CTs (as monotherapy or in combination) were identified for 70 ASs. Of these, 52% were at phases 1, 1/2, and 2 aimed at PK/PD/dosing activity. The remaining ones also included efficacy. Phase 3 studies were limited. Studies were completed for 14 ASs and suspended for 11. The highest rate of ASs involved in CTs was observed in the RAS-MAPK-MEK and VEGF groups. A total of 37 ASs were granted with a PIP, of which 14 involved NBL, 41 ASs with a waiver, and 18 ASs with both PIPs and waivers, with the PIP covering pediatric indications different from the adult ones. In almost all the PIPs, preclinical studies were required, together with early-phase CTs often including efficacy evaluation. Two PIPs were terminated because of negative study results, and eight PIPs are in progress. Variations in the SmPC were made for larotrectinib sulfate/Vitrakvi® and entrectinib/Rozlytrek® with the inclusion of a new indication. For both, the related PIPs are still ongoing. The orphan designation has been largely adopted, while PRIME designation has been less implemented.DiscussionSeveral ASs entered early phase CTs but less than one out of four were included in a regulatory process, and only two were granted a pediatric indication extension. Our results confirm that it is necessary to identify a more efficient, less costly, and time-consuming “pediatric developmental model” integrating predictive preclinical study and innovative clinical study designs. Furthermore, stricter integration between scientific and regulatory efforts should be promoted.
Histopathological differences between vitiligo and lichen sclerosus et atrophicus using quantitative immunohistochemical analysis
Authors: Park Young Joon , Lee Heera , Park Hyoung Soo , Kim You Chan 
Published: July 2023

IntroductionLichen sclerosus et atrophicus (LS) is rare skin condition characterized by the presence of whitish patches primarily affecting the genital and perianal areas, though it can occur other parts of the body. LS may result in skin depigmentation without textural changes and should be differentiated from vitiligo. However, the histopathological features of hypopigmentation during vitiligo and LS have rarely been compared and have not been precisely described using quantitative immunohistochemical analysis. This study, therefore, aimed to investigate and compare the pigmentary characteristics of LS and vitiligo lesions using histochemical and immunohistochemical staining.MethodsWe included 31 and 46 patients diagnosed with LS and vitiligo, respectively, at Ajou University Hospital between March 2009 and March 2020 in this study. Their medical charts and skin biopsy specimens were retrospectively reviewed. Additionally, Fontana–Masson staining for melanin and immunohistochemical staining for Melan-A, NKI/beteb, tyrosinase, and microphthalmia-associated transcription factor was performed.ResultsThe melanin content, as well as the number of melanocytes was, in general, significantly higher in the epidermis of patients in the LS group compared with that in the vitiligo group. However, 22.6% of LS tissues showed less melanin pigmentation, 25.8% of LS specimens exhibited a lower number of melanocytes, and 29.0% of LS specimens demonstrated less melanocyte activity when compared with the average of vitiligo specimens.ConclusionAs lower melanin pigmentation and the near absence number of melanocytes were also observed in several LS specimens, both the clinical and histological findings must be comprehensively reviewed to differentiate vitiligo from LS.
TRIM3 attenuates cytokine storm caused by Dabie bandavirus via promoting Toll-like receptor 3 degradation
Authors: Jin Ke , Dai Yan , Ouyang Ke , Huang Huaying , Jiang Zhengyi , Yang Zhan , Zhou Tingting , Lin Hong , Wang Chunhui , Wang Chunyan , Sun Xuewei , Lu Dafeng , Liu Xiaoguang , Hu Nannan , Zhu Chuanlong , Zhu Jin , Li Jun 
Published: July 2023

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by the Dabie bandavirus (DBV), and it has become a global public health threat. Cytokine storm is considered to be an important pathogenesis of critical SFTS. Tripartite motif-containing 3 (TRIM3), as a member of the TRIM protein family, may contribute to the regulation of the immune and inflammatory responses after viral infection. However, whether TRIM3 plays a major role in the pathogenesis of SFTS has not yet been investigated.MethodsTRIM3 mRNA levels were detected in PBMCs between 29 SFTS patients and 29 healthy controls by qRT-PCR. We established the pathogenic IFNAR−/− SFTS mouse model successfully by inoculating subcutaneously with DBV and testing the expression levels of TRIM3 mRNA and protein by qRT-PCR and immunofluorescence in the livers, spleens, lungs, and kidneys. TRIM3OE THP-1 cells and peritoneal macrophages extracted from TRIM3−/− mice were infected with DBV. The effect of TRIM3 on cytokines was detected by qRT-PCR and ELISA. Then we examined Toll-like receptor 3 (TLR3) and protein phosphorylation in the MAPK pathway after DBV infection using Western blot. Flow cytometry was used to verify TLR3 expression on peripheral blood monocytes in SFTS patients. We further explored the interaction between TRIM3 and TLR3 using CO-IP and Western blot.ResultsCompared to healthy controls, TRIM3 mRNA expression in PBMCs is decreased in SFTS patients, especially in severe cases. TRIM3 mRNA and protein were synchronously reduced in the livers, spleens, lungs, and kidney tissues of the IFNAR−/− SFTS mice model. In the DBV-infected cell model, TRIM3 overexpression can inhibit the DBV-induced release of IL-1β, IL-6, and TNF-α, the expression of TLR3, and protein phosphorylation in the MAPK pathway, which plays an anti-inflammatory role, while TRIM3 deficiency exacerbates the pro-inflammatory effects. We further found that TRIM3 can promote TLR3 degradation through K48-linked ubiquitination.ConclusionTRIM3 can inhibit the production of cytokines by regulating the degradation of TLR3 through K48-linked ubiquitination, which can be a therapeutic target for improving the prognosis of SFTS.
Wild-type Lactococcus lactis producing bacteriocin-like prophage lysins
Authors: Takala Timo M. , Mokhtari Samira , Ahonen Susanna L. , Wan Xing , Saris Per E. J. 
Published: July 2023

IntroductionLactococcus is a genus of lactic acid bacteria used in the dairy industry as a starter. Lactococci have been found to produce altogether more than 40 different bacteriocins, ribosomally synthesized antimicrobial proteins. All known Lactococcus spp. bacteriocins belong to classes I and II, which are mainly heat-resistant peptides. No class III bacteriocins, bigger heat-sensitive proteins, including phage tail-like bacteriocins, have been found from the Lactococcus spp. Unlike phage tail-like bacteriocins, prophage lysins have not been regarded as bacteriocins, possibly because phage lysins contribute to autolysis, degrading the host's own cell wall.MethodsWild-type Lactococcus lactis strain LAC460, isolated from spontaneously fermented idli batter, was examined for its antimicrobial activity. We sequenced the genome, searched phage lysins from the culture supernatant, and created knock-out mutants to find out the source of the antimicrobial activity.Results and discussionThe strain LAC460 was shown to kill other Lactococcus strains with protease- and heat-sensitive lytic activity. Three phage lysins were identified in the culture supernatant. The genes encoding the three lysins were localized in different prophage regions in the chromosome. By knock-out mutants, two of the lysins, namely LysL and LysP, were demonstrated to be responsible for the antimicrobial activity. The strain LAC460 was found to be resistant to the lytic action of its own culture supernatant, and as a consequence, the phage lysins could behave like bacteriocins targeting and killing other closely related bacteria. Hence, similar to phage tail-like bacteriocins, phage lysin-like bacteriocins could be regarded as a novel type of class III bacteriocins.
Identification of novel gene signatures and immune cell infiltration in intervertebral disc degeneration using bioinformatics analysis
Authors: Tang Tao , He Zhongyuan , Zhu Zhengya , Wang Fuan , Chen Hongkun , Zhang Fu , Zhou Jiaxiang , Wang Jianmin , Li Baoliang , Liu Xizhe , Zhou Zhiyu , Liu Shaoyu 
Published: July 2023

Background: Intervertebral disc degeneration (IDD) is the leading cause of lower back pain, and an overall understanding of the molecular mechanisms related to IDD is still lacking. The purpose of this study was to explore gene signatures and immune cell infiltration related to IDD via bioinformatics analysis.Methods: A total of five expression profiles of mRNA and non-coding RNA were downloaded from the Gene Expression Omnibus (GEO) database. The potentially involved lncRNA/circRNA–miRNA–mRNA networks and protein-protein interaction networks were constructed by miRNet, circBank, STRING, and the Cytoscape database. Gene ontology, Kyoto Encyclopaedia of Genes and Genomes Analysis, Gene Set Enrichment Analysis, Gene Set Variation Analysis, Immune Infiltration Analysis, and Drug-Gene Interaction were used to analyse the top 20 hub genes. RT-qPCR was conducted to confirm the 12 differential expressions of genes both in the nucleus pulposus and annulus fibrosus tissuesResults: There were 346 differentially expressed mRNAs, 12 differentially expressed miRNAs, 883 differentially expressed lncRNAs, and 916 differentially expressed circRNAs in the GEO database. Functional and enrichment analyses revealed hub genes associated with platelet activation, immune responses, focal adhesion, and PI3K-Akt signalling. The apoptotic pathway, the reactive oxygen species pathway, and oxidative phosphorylation play an essential role in IDD. Immune infiltration analysis demonstrated that the Treg cells had significant infiltration, and three levels of immune cells, including dendritic cells, Th2 cells, and tumour-infiltrating lymphocytes, were inhibited in IDD. Drug-gene interaction analysis showed that COL1A1 and COL1A2 were targeted by collagenase clostridium histolyticum, ocriplasmin, and PDGFRA was targeted by 66 drugs or molecular compounds. Finally, 24 cases of IDD tissues and 12 cases of normal disc tissues were collected, and the results of RT-qPCR were consistent with the bioinformatics results.Conclusion: Our data indicated that the 20 hub genes and immune cell infiltration were involved in the pathological process of IDD. In addition, the PDGFRA and two potential drugs were found to be significant in IDD development.