Efficacy and safety of Brolucizumab for neovascular age-related macular degeneration: a systematic review and meta-analysis
Background To evaluate the efficacy and safety of Brolucizumab for neovascular age-related macular degeneration (n-AMD) through a systematic review and meta-analysis. Materials and Methods Cochrane, PubMed, Embase, and Web of Science databases were comprehensively searched for relevant studies. Stata and RevMan5.4 were applied for meta-analysis and risk of bias assessment. Data on the best-corrected visual acuity (BCVA), central subfield thickness (CSFT), presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), participants with ≥1 serious adverse events, and participants with ≥1 adverse events were analyzed. Results Six studies were finally included. Meta-analysis showed statistical differences in BCVA [SMD = −0.65, 95% CI [−0.17 to −0.23], P < 0.05], the presence of IRF and/or SRF [RR = 0.67, 95% CI [0.56–0.79], P < 0.05], and the safety of participants with ≥1 serious adverse events [RR = 0.57, 95% CI [0.39–0.84], P < 0.05] between the experimental group and the control group. However, no statistical differences were observed in CSFT [SMD = −1.16, 95% CI [−2.79 to 0.47], P > 0.05] or the safety of participants with ≥1 adverse events [RR = 1.07, 95% CI [0.97–1.17], P > 0.05]. Conclusions Compared to other anti-VEGF drugs such as Aflibercept and Ranibizumab, intravitreal injection of 6 mg Brolucizumab is more effective and safer for n-AMD, especially in the presence of IRF and/or SRF, and for participants with ≥1 serious adverse events.
Dou et al. (2024) Efficacy and safety of Brolucizumab for neovascular age-related macular degeneration: a systematic review and meta-analysis. PeerJ 12:e17561 https://doi.org/10.7717/peerj.17561
Retrospective study of a novel hematological parameter for predicting the survival of patients with nasopharyngeal carcinoma
Purpose This study aims to explore the prognostic values of routine pre-treatment hematological parameters in patients with nasopharyngeal carcinoma (NPC). Methods The hematological parameters and clinical data of patients with NPC were collected from January 2012 to December 2013 at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. The survival statistics were obtained by regularly following-up the patients. The cut-off values for the hematological parameters were calculated using X-tile software. SPSS version 24.0 was used for the statistical analysis. The relationship between the hematological parameters and the prognosis of patients with NPC was analyzed using the Kaplan–Meier method and Cox multivariate regression. The discriminating abilities of the factors, which predict the prognosis, were evaluated by utilizing the receiver operating characteristic (ROC) area under the curve (AUC). Results This study included 179 patients with NPC. Multivariate analysis shows that pretreatment platelet-to-lymphocyte ratio (PLR; hazard ratio; HR = 0.44, 95% CI [0.21–0.91], p = 0.029), serum albumin (ALB; HR = 2.49, 95% CI [1.17–5.30], p = 0.018), and globulin (GLO; HR = 0.44, 95% CI [0.21–0.90], p = 0.024) are independent predictors for 5-year overall survival (OS) in patients with NPC. In addition, pre-treatment PLR (HR = 0.47, 95% CI [0.25–0.90], p = 0.022) and pre-treatment GLO (HR = 0.37, 95% CI [0.19–0.72], p = 0.001) are associated with 5-year progression-free survival (PFS) in patients with NPC. Based on the results of the multivariate analysis, we proposed a new biomarker GLO-PLR, which is observably correlated with the T stage, N stage and clinical stage in patients with NPC. The OS resolving ability of the GLO-PLR evaluated by AUC is 0.714, which is better than those of GLO and PLR. The PFS resolving ability of the GLO-PLR evaluated by AUC was 0.696, which is also better than those of GLO and PLR. Conclusion Pre-treatment PLR, ALB, and GLO are independent predictors of 5-year OS in patients with NPC, where PLR and GLO are also independent predictors of 5-year FPS. Compared with other hematological parameters, the proposed GLO-PLR is an inexpensive, effective, objective, and easy-to-measure marker for predicting the prognosis of NPC.
Tang et al. (2024) Retrospective study of a novel hematological parameter for predicting the survival of patients with nasopharyngeal carcinoma. PeerJ 12:e17573 https://doi.org/10.7717/peerj.17573
Lokiceratops rangiformis gen. et sp. nov. (Ceratopsidae: Centrosaurinae) from the Campanian Judith River Formation of Montana reveals rapid regional radiations and extreme endemism within centrosaurine dinosaurs
The Late Cretaceous of western North America supported diverse dinosaur assemblages, though understanding patterns of dinosaur diversity, evolution, and extinction has been historically limited by unequal geographic and temporal sampling. In particular, the existence and extent of faunal endemism along the eastern coastal plain of Laramidia continues to generate debate, and finer scale regional patterns remain elusive. Here, we report a new centrosaurine ceratopsid, Lokiceratops rangiformis, from the lower portion of the McClelland Ferry Member of the Judith River Formation in the Kennedy Coulee region along the Canada-USA border. Dinosaurs from the same small geographic region, and from nearby, stratigraphically equivalent horizons of the lower Oldman Formation in Canada, reveal unprecedented ceratopsid richness, with four sympatric centrosaurine taxa and one chasmosaurine taxon. Phylogenetic results show that Lokiceratops, together with Albertaceratops and Medusaceratops, was part of a clade restricted to a small portion of northern Laramidia approximately 78 million years ago. This group, Albertaceratopsini, was one of multiple centrosaurine clades to undergo geographically restricted radiations, with Nasutuceratopsini restricted to the south and Centrosaurini and Pachyrostra restricted to the north. High regional endemism in centrosaurs is associated with, and may have been driven by, high speciation rates and diversity, with competition between dinosaurs limiting their geographic range. High speciation rates may in turn have been driven in part by sexual selection or latitudinally uneven climatic and floral gradients. The high endemism seen in centrosaurines and other dinosaurs implies that dinosaur diversity is underestimated and contrasts with the large geographic ranges seen in most extant mammalian megafauna.
Loewen et al. (2024) Lokiceratops rangiformis gen. et sp. nov. (Ceratopsidae: Centrosaurinae) from the Campanian Judith River Formation of Montana reveals rapid regional radiations and extreme endemism within centrosaurine dinosaurs. PeerJ 12:e17224 https://doi.org/10.7717/peerj.17224
Gypenosides exert cardioprotective effects by promoting mitophagy and activating PI3K/Akt/GSK-3β/Mcl-1 signaling
Background Gynostemma pentaphyllum (Thunb.) Makino, a well-known edible and medicinal plant, has anti-aging properties and is used to treataging-associated conditions such as diabetes, metabolic syndrome, and cardiovascular diseases. Gypenosides (GYPs) are the primary constituents of G. pentaphyllum. Increasing evidence indicates that GYPs are effective at preserving mitochondrial homeostasis and preventing heart failure (HF). This study aimed to uncover the cardioprotective mechanisms of GYPs related to mitochondrial regulation. Methods The bioactive components in GYPs and the potential targets in treating HF were obtained and screened using the network pharmacology approach, followed by drug-disease target prediction and enrichment analyses. The pharmacological effects of GYPs in cardioprotection, mitochondrial function, mitochondrial quality control, and underlying mechanisms were further investigated in Doxorubicin (Dox)-stimulated H9c2 cardiomyocytes. Results A total of 88 bioactive compounds of GYPs and their respective 71 drug-disease targets were identified. The hub targets covered MAPK, EGFR, PI3KCA, and Mcl-1. Enrichment analysis revealed that the pathways primarily contained PI3K/Akt, MAPK, and FoxO signalings, as well as calcium regulation, protein phosphorylation, apoptosis, and mitophagy process. In Dox-stimulated H9c2 rat cardiomyocytes, pretreatment with GYPs increased cell viability, enhanced cellular ATP content, restored basal oxygen consumption rate (OCR), and improved mitochondrial membrane potential (MMP). Furthermore, GYPs improved PINK1/parkin-mediated mitophagy without influencing mitochondrial fission/fusion proteins and the autophagic LC3 levels. Mechanistically, the phosphorylation of PI3K, Akt, GSK-3β, and the protein level of Mcl-1 was upregulated by GYP treatment. Conclusion Our findings reveal that GYPs exert cardioprotective effects by rescuing the defective mitophagy, and PI3K/Akt/GSK-3β/Mcl-1 signaling is potentially involved in this process.
Zheng et al. (2024) Gypenosides exert cardioprotective effects by promoting mitophagy and activating PI3K/Akt/GSK-3β/Mcl-1 signaling. PeerJ 12:e17538 https://doi.org/10.7717/peerj.17538
Mitochondrial DNA and Y chromosome reveal the genetic structure of the native Polish Konik horse population
Polish Konik remains one of the most important horse breeds in Poland. The primitive, native horses with a stocky body and mouse-like coat color are protected by a conservation program, while their Polish population consists of about 3,480 individuals, representing 16 dam and six sire lines. To define the population’s genetic structure, mitochondrial DNA and Y chromosome sequence variables were identified. The mtDNA whole hypervariable region analysis was carried out using the Sanger sequencing method on 233 Polish Koniks belonging to all dam lines, while the Y chromosome analysis was performed with the competitive allele-specific PCR genotyping method on 36 horses belonging to all sire lines. The analysis of the mtDNA hypervariable region detected 47 SNPs, which assigned all tested horses to 43 haplotypes. Most dam lines presented more than one haplotype; however, five dam lines were represented by only one haplotype. The haplotypes were classified into six (A, B, E, J, G, R) recognized mtDNA haplogroups, with most horses belonging to haplogroup A, common among Asian horse populations. Y chromosome analysis allocated Polish Koniks in the Crown group, condensing all modern horse breeds, and divided them into three haplotypes clustering with coldblood breeds (28 horses), warmblood breeds (two horses), and Duelmener Pony (six horses). The clustering of all Wicek sire line stallions with Duelmener horses may suggest a historical relationship between the breeds. Additionally, both mtDNA and Y chromosome sequence variability results indicate crossbreeding before the studbooks closure or irregularities in the pedigrees occurred before the DNA testing introduction.
Musiał et al. (2024) Mitochondrial DNA and Y chromosome reveal the genetic structure of the native Polish Konik horse population. PeerJ 12:e17549 https://doi.org/10.7717/peerj.17549
Identifying the source rookery of green turtles (Chelonia mydas) found in feeding grounds around the Korean Peninsula
Determining the genetic diversity and source rookeries of sea turtles collected from feeding grounds can facilitate effective conservation initiatives. To ascertain the genetic composition and source rookery, we examined a partial sequence of the mitochondrial control region (CR, 796 bp) of 40 green turtles (Chelonia mydas) collected from feeding grounds around the Korean Peninsula between 2014 and 2022. We conducted genetic and mixed-stock analyses (MSA) and identified 10 CR haplotypes previously reported in Japanese populations. In the haplotype network, six, three, and one haplotype(s) grouped with the Japan, Indo-Pacific, and Central South Pacific clades, respectively. The primary rookeries of the green turtles were two distantly remote sites, Ogasawara (OGA) and Central Ryukyu Island (CRI), approximately 1,300 km apart from each other. Comparing three parameters (season, maturity, and specific feeding ground), we noted that OGA was mainly associated with summer and the Jeju Sea, whereas CRI was with fall and the East (Japan) Sea ground. The maturity did not show a distinct pattern. Our results indicate that green turtles in the feeding grounds around the Korean Peninsula originate mainly from the Japan MU and have genetic origins in the Japan, Indo-Pacific, and Central South Pacific clades. Our results provide crucial insights into rookeries and MUs, which are the focus of conservation efforts of the Republic of Korea and potential parties to collaborate for green turtle conservation.
Park et al. (2024) Identifying the source rookery of green turtles (Chelonia mydas) found in feeding grounds around the Korean Peninsula. PeerJ 12:e17560 https://doi.org/10.7717/peerj.17560
VOE: automated analysis of variant epitopes of SARS-CoV-2 for the development of diagnostic tests or vaccines for COVID-19
Background The development of serodiagnostic tests and vaccines for COVID-19 depends on the identification of epitopes from the SARS-CoV-2 genome. An epitope is the specific part of an antigen that is recognized by the immune system and can elicit an immune response. However, when the genetic variants contained in epitopes are used to develop rapid antigen tests (Ag-RDTs) and DNA or RNA vaccines, test sensitivity and vaccine efficacy can be low. Methods Here, we developed a “variant on epitope (VOE)” software, a new Python script for identifying variants located on an epitope. Variant analysis and sensitivity calculation for seven recommended epitopes were processed by VOE. Variants in 1,011 Omicron SRA reads from two variant databases (BCFtools and SARS-CoV-2-Freebayes) were processed by VOE. Results A variant with HIGH or MODERATE impact was found on all epitopes from both variant databases except the epitopes KLNDLCFTNV, RVQPTES, LKPFERD, and ITLCFTLKRK on the S gene and ORF7a gene. All epitope variants from the BCFtools and SARS-CoV-2 Freebayes variant databases showed about 100% sensitivity except epitopes APGQTGK and DSKVGGNYN on the S gene, which showed respective sensitivities of 28.4866% and 6.8249%, and 87.7349% and 71.1177%. Conclusions Therefore, the epitopes KLNDLCFTNV, RVQPTES, LKPFERD, and ITLCFTLKRK may be useful for the development of an epitope-based peptide vaccine and GGDGKMKD on the N gene may be useful for the development of serodiagnostic tests. Moreover, VOE can also be used to analyze other epitopes, and a new variant database for VOE may be further established when a new variant of SARS-CoV-2 emerges.
Lee et al. (2024) VOE: automated analysis of variant epitopes of SARS-CoV-2 for the development of diagnostic tests or vaccines for COVID-19. PeerJ 12:e17504 https://doi.org/10.7717/peerj.17504
A quantitative test of the “Ecomorphotype Hypothesis” for fossil true seals (Family Phocidae)
The fossil record of true seals (Family Phocidae) is mostly made up of isolated bones, some of which are type specimens. Previous studies have sought to increase referral of non-overlapping and unrelated fossils to these taxa using the ‘Ecomorphotype Hypothesis’, which stipulates that certain differences in morphology between taxa represent adaptations to differing ecology. On this basis, bulk fossil material could be lumped to a specific ecomorphotype, and then referred to species in that ecomorphotype, even if they are different bones. This qualitative and subjective method has been used often to expand the taxonomy of fossil phocids, but has never been quantitatively tested. We test the proposed ecomorphotypes using morphometric analysis of fossil and extant northern true seal limb bones, specifically principal components analysis and discriminant function analysis. A large amount of morphological overlap between ecomorphotypes, and poor discrimination between them, suggests that the ‘Ecomorphotype Hypothesis’ is not a valid approach. Further, the analysis failed to assign fossils to ecomorphotypes designated in previous studies, with some fossils from the same taxa being designated as different ecomorphotypes. The failure of this approach suggests that all fossils referred using this method should be considered to have unknown taxonomic status. In light of this, and previous findings that phocid limb bones have limited utility as type specimens, we revise the status of named fossil phocid species. We conclude that the majority of named fossil phocid taxa should be considered nomina dubia.
Rule et al. (2024) A quantitative test of the “Ecomorphotype Hypothesis” for fossil true seals (Family Phocidae). PeerJ 12:e17592 https://doi.org/10.7717/peerj.17592
The role of monocyte chemoattractant protein-1 (MCP-1) as an immunological marker for patients with leprosy: a systematic literature review
Leprosy, a significant global health concern affecting primarily the peripheral nerves and integumentary system, is influenced by the host immune system’s response, affecting its pathology, disease progression, and reaction occurrence. MCP-1, integral to leprosy’s immunological processes, holds promise as a diagnostic tool and predictor of reaction occurrence. This systematic review aimed to investigate MCP-1’s involvement in leprosy. Literature search, employing specified MeSH keywords, covered databases such as PubMed, Scopus, ScienceDirect, and Wiley Online Library until September 30th, 2023, yielding seventeen relevant studies. Assessing each study’s quality with the Newcastle-Ottawa Scale (NOS) and investigating bias using the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS), a narrative synthesis compiled findings. Seventeen distinct studies were included, each characterized by diverse designs, sample sizes, demographics, and outcome measures, highlighting MCP-1’s potential in diagnosing leprosy, differentiating it from control groups, and discerning leprosy types. Furthermore, MCP-1 shows promise in predicting leprosy reversal reactions. Although MCP-1 offers clinical benefits, including early diagnosis and type differentiation, further research with larger sample sizes and standardized methodologies is imperative to confirm its diagnostic utility fully.
Prakoeswa et al. (2024) The role of monocyte chemoattractant protein-1 (MCP-1) as an immunological marker for patients with leprosy: a systematic literature review. PeerJ 12:e17400 https://doi.org/10.7717/peerj.17400
Bioinformatic analysis and experimental validation of six cuproptosis-associated genes as a prognostic signature of breast cancer
Background Breast carcinoma (BRCA) is a life-threatening malignancy in women and shows a poor prognosis. Cuproptosis is a novel mode of cell death but its relationship with BRCA is unclear. This study attempted to develop a cuproptosis-relevant prognostic gene signature for BRCA. Methods Cuproptosis-relevant subtypes of BRCA were obtained by consensus clustering. Differential expression analysis was implemented using the ‘limma’ package. Univariate Cox and multivariate Cox analyses were performed to determine a cuproptosis-relevant prognostic gene signature. The signature was constructed and validated in distinct datasets. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were also conducted using the prognostic signature to uncover the underlying molecular mechanisms. ESTIMATE and CIBERSORT algorithms were applied to probe the linkage between the gene signature and tumor microenvironment (TME). Immunotherapy responsiveness was assessed using the Tumor Immune Dysfunction and Exclusion (TIDE) web tool. Real-time quantitative PCR (RT-qPCR) was performed to detect the expressions of cuproptosis-relevant prognostic genes in breast cancer cell lines. Results Thirty-eight cuproptosis-associated differentially expressed genes (DEGs) in BRCA were mined by consensus clustering and differential expression analysis. Based on univariate Cox and multivariate Cox analyses, six cuproptosis-relevant prognostic genes, namely SAA1, KRT17, VAV3, IGHG1, TFF1, and CLEC3A, were mined to establish a corresponding signature. The signature was validated using external validation sets. GSVA and GSEA showed that multiple cell cycle-linked and immune-related pathways along with biological processes were associated with the signature. The results ESTIMATE and CIBERSORT analyses revealed significantly different TMEs between the two Cusig score subgroups. Finally, RT-qPCR analysis of cell lines further confirmed the expressional trends of SAA1, KRT17, IGHG1, and CLEC3A. Conclusion Taken together, we constructed a signature for projecting the overall survival of BRCA patients and our findings authenticated the cuproptosis-relevant prognostic genes, which are expected to provide a basis for developing prognostic molecular biomarkers and an in-depth understanding of the relationship between cuproptosis and BRCA.
Chen et al. (2024) Bioinformatic analysis and experimental validation of six cuproptosis-associated genes as a prognostic signature of breast cancer. PeerJ 12:e17419 https://doi.org/10.7717/peerj.17419