Study of LY9 as a potential biomarker for prognosis and prediction of immunotherapy efficacy in lung adenocarcinoma
Background Lymphocyte antigen 9 (LY9) participates in the development of several tumors and diseases but has not been reported yet in lung adenocarcinoma (LUAD). Methods First, we analyzed the expression and prognostic value of LY9 in pan-cancer, including LUAD. Additionally, we conducted a correlation analysis of LY9 expression in LUAD with immune cell infiltration using the TIMER database and the CIBERSORT algorithm, and with immune checkpoints using the GEPIA database. Also, we constructed a potential ceRNA network for LY9. Furthermore, we explored LY9-related pathways by Gene Set Enrichment Analysis (GSEA). Finally, validation of differential expression at the mRNA level was obtained from the GEO database. We collected LUAD tissues for Quantitative Real-time PCR (qRT-PCR) to verify the expression of LY9, CD8, and CD4 and calculated the correlation between them. We also conducted immunohistochemistry (IHC) to verify the protein expression of LY9. Results Results showed that LY9 was highly expressed in various tumors, including LUAD. Besides, patients with high LY9 expression presented longer overall survival (OS) and more multiple lymphocyte infiltrations. The expression of LY9 in LUAD strongly and positively correlates with multiple immune cell infiltration and immune checkpoints. The functional enrichment analysis indicated that LY9 was involved in multiple immune-related pathways and non-small cell lung cancer. Moreover, a ceRNA regulatory network of LINC00943-hsa-miR-141-3p-LY9 might be involved. Finally, GSE68465 dataset confirmed differential expression of LY9 mRNA levels in LUAD and the qRT-PCR results verified LY9 had a strong and positive correlation with CD4 and CD8 T cells. Unfortunately, IHC did not detect the expression of LY9 protein level in tumor tissues and WB experiments validated the protein expression of LY9 in the OCI-AML-2 cell line. Conclusions Therefore, we hypothesized that LY9 could serve as a potential, novel prognostic biomarker for LUAD and could predict immunotherapy efficacy at the mRNA level.
Deng et al. (2024) Study of LY9 as a potential biomarker for prognosis and prediction of immunotherapy efficacy in lung adenocarcinoma. PeerJ 12:e17816 https://doi.org/10.7717/peerj.17816
The contribution of energy systems during 15-second sprint exercise in athletes of different sports specializations
Background Long-term adaptations and ongoing training seem to modify the energy system contribution in highly trained individuals. We aimed to compare the energy metabolism profile during sprint exercise in athletes of different specialties. Methods Endurance (n = 17, 20.3 ± 6.0 yrs), speed-power (n = 14, 20.3 ± 2.5 yrs), and mixed (n = 19, 23.4 ± 4.8 yrs) athletes performed adapted 15-second all-out test before and after a general preparation training period. The contribution of phosphagen, glycolytic, and aerobic systems was calculated using the three-component PCr-LA-O2 method. Results Between-group differences were observed in the contribution of energy systems in the first and second examinations. The proportions were 47:41:12 in endurance, 35:57:8 in team sports, and 45:48:7 in speed-power athletes. Endurance athletes differed in the phosphagen (p < 0.001) and glycolytic systems (p = 0.006) from team sports and in the aerobic system from speed-power athletes (p = 0.003). No substantial shifts were observed after the general preparatory phase, except a decrease in aerobic energy contribution in team sports athletes (p = 0.048). Conclusion Sports specialization and metabolic profile influence energy system contribution during sprint exercise. Highly trained athletes show a stable energy profile during the general preparation phase, indicative of long-term adaptation, rather than immediate training effects.
Archacki et al. (2024) The contribution of energy systems during 15-second sprint exercise in athletes of different sports specializations. PeerJ 12:e17863 https://doi.org/10.7717/peerj.17863
Long-term passage impacts human dental pulp stem cell activities and cell response to drug addition in vitro
Background Dental pulp stem cells (DPSCs) possess mesenchymal stem cell characteristics and have potential for cell-based therapy. Cell expansion is essential to achieve sufficient cell numbers. However, continuous cell replication causes cell aging in vitro, which usually accompanies and potentially affect DPSC characteristics and activities. Continuous passaging could alter susceptibility to external factors such as drug treatment. Therefore, this study sought to investigate potential outcome of in vitro passaging on DPSC morphology and activities in the absence or presence of external factor. Methods Human DPSCs were subcultured until reaching early passages (P5), extended passages (P10), and late passages (P15). Cells were evaluated and compared for cell and nuclear morphologies, cell adhesion, proliferative capacity, alkaline phosphatase (ALP) activity, and gene expressions in the absence or presence of external factor. Alendronate (ALN) drug treatment was used as an external factor. Results Continuous passaging of DPSCs gradually lost their normal spindle shape and increased in cell and nuclear sizes. DPSCs were vulnerable to ALN. The size and shape were altered, leading to morphological abnormality and inhomogeneity. Long-term culture and ALN interfered with cell adhesion. DPSCs were able to proliferate irrespective of cell passages but the rate of cell proliferation in late passages was slower. ALN at moderate dose inhibited cell growth. ALN caused reduction of ALP activity in early passage. In contrast, extended passage responded differently to ALN by increasing ALP activity. Late passage showed higher collagen but lower osteocalcin gene expressions compared with early passage in the presence of ALN. Conclusion An increase in passage number played critical role in cell morphology and activities as well as responses to the addition of an external factor. The effects of cell passage should be considered when used in basic science research and clinical applications.
Patntirapong et al. (2024) Long-term passage impacts human dental pulp stem cell activities and cell response to drug addition in vitro. PeerJ 12:e17913 https://doi.org/10.7717/peerj.17913
DNA methylation and gene expression profiling reveal potential association of retinol metabolism related genes with hepatocellular carcinoma development
Background Aberrant DNA methylation patterns play a critical role in the development of hepatocellular carcinoma (HCC). However, the molecular mechanisms associated with these aberrantly methylated genes remain unclear. This study aimed to comprehensively investigate the methylation-driven gene expression alterations in HCC using a multi-omics dataset. Methods Whole genome bisulfite sequencing (WGBS) and RNA sequencing (RNA-seq) techniques were used to assess the methylation and gene expression profiles of HCC tissues (HCCs) and normal adjacent tissues (NATs). The candidate genes’ potential function was further investigated using single-cell RNA sequencing (scRNA seq) data. Results We observed widespread hypomethylation in HCCs compared to NATs. Methylation levels in distinct genomic regions exhibited significant differences between HCCs and NATs. We identified 247,632 differentially methylated regions (DMRs) and 4,926 differentially expressed genes (DEGs) between HCCs and NATs. Integrated analysis of DNA methylation and RNA-seq data identified 987 methylation-driven candidate genes, with 970 showing upregulation and 17 showing downregulation. Four genes involved in the retinol metabolic pathway, namely ADH1A, CYP2A6, CYP2C8, and CYP2C19, were identified as hyper-downregulated genes. Their expression levels could stratify HCCs into three subgroups with distinct survival outcomes, immune cell infiltration, and tumor microenvironments. Validation of these findings in an independent dataset yielded similar outcomes, confirming the high concordance and potential prognostic value of these genes. ScRNA seq data revealed the low expression of these genes in immune cells, emphasizing their role in promoting malignant cell proliferation and migration. In conclusion, this study provides insights into the molecular characteristics of HCC, revealing the involvement of retinol metabolism-related genes in the development and progression of HCC. These findings have implications for HCC diagnosis, prognosis prediction, and the development of therapeutic targets.
Zhao et al. (2024) DNA methylation and gene expression profiling reveal potential association of retinol metabolism related genes with hepatocellular carcinoma development. PeerJ 12:e17916 https://doi.org/10.7717/peerj.17916
Changes of Tamarix austromongolica forests with embankment dams along the Laizhou bay
Background Embankment dams were built south of the Laizhou bay in China for controlling storm surge disasters, but they are not enough to replace coastal forests in protecting the land. This study was designed to evaluate the effects of embankment dams on natural forests dominated by Tamarix austromongolica and test whether the dam-shrub system is a preferable updated defense. Methods Coastal forests on two typical flats, one before and one behind embankment dams, were investigated using quadrats and lines. Land bareness, vegetation composition and species co-occurrence were assessed; structures of T. austromongolica populations were evaluated; and spatial patterns of the populations were analyzed using Ripley’s K and K1,2 functions. Results In the area before embankment dams, 84.8% of T. austromongolica were juveniles (basal diameter ≤ 3 cm), and 15.2% were adults (basal diameter > 3 cm); behind the dams, 52.9% were juveniles, and 47.1 were adults. In the area before the dams, the land bareness was 13.7%, four species occurred, and they all were ready to co-occur with T. austromongolica; behind the dams, the land bareness was 0%, and 16 species occurred whereas they somewhat resisted co-occurrence with T. austromongolica. In the area before the dams, the T. austromongolica population was aggregated in heterogeneous patches, and the juveniles tended to co-occur with the adults; behind the dams, they were over-dispersed as nearly uniform distributions, while the juveniles could recruit and were primarily independent of the adults. These results indicate that the T. austromongolica species did not suffer from the unnatural dams, but benefited somehow in population expansion and development. Overall, the T. austromongolica species can adapt to artificial embankment dams to create a synthetic defense against storm surges.
Yang et al. (2024) Changes of Tamarix austromongolica forests with embankment dams along the Laizhou bay. PeerJ 12:e17934 https://doi.org/10.7717/peerj.17934
Broad-scale ecological niches of pathogens vectored by the ticks Ixodes scapularis and Amblyomma americanum in North America
Environmental dimensions, such as temperature, precipitation, humidity, and vegetation type, influence the activity, survival, and geographic distribution of tick species. Ticks are vectors of various pathogens that cause disease in humans, and Ixodes scapularis and Amblyomma americanum are among the tick species that transmit pathogens to humans across the central and eastern United States. Although their potential geographic distributions have been assessed broadly via ecological niche modeling, no comprehensive study has compared ecological niche signals between ticks and tick-borne pathogens. We took advantage of National Ecological Observatory Network (NEON) data for these two tick species and associated bacteria pathogens across North America. We used two novel statistical tests that consider sampling and absence data explicitly to perform these explorations: a univariate analysis based on randomization and resampling, and a permutational multivariate analysis of variance. Based on univariate analyses, in Amblyomma americanum, three pathogens (Borrelia lonestari, Ehrlichia chaffeensis, and E. ewingii) were tested; pathogens showed nonrandom distribution in at least one environmental dimension. Based on the PERMANOVA test, the null hypothesis that the environmental position and variation of pathogen-positive samples are equivalent to those of A. americanum could not be rejected for any of the pathogens, except for the pathogen E. ewingii in maximum and minimum vapor pressure and minimum temperature. For Ixodes scapularis, six pathogens (A. phagocytophilum, Babesia microti, Borrelia burgdorferi sensu lato, B. mayonii, B. miyamotoi, and Ehrlichia muris-like) were tested; only B. miyamotoi was not distinct from null expectations in all environmental dimensions, based on univariate tests. In the PERMANOVA analyses, the pathogens departed from null expectations for B. microti and B. burgdorferi sensu lato, with smaller niches in B. microti, and larger niches in B. burgdorferi sensu lato, than the vector. More generally, this study shows the value of large-scale data resources with consistent sampling methods, and known absences of key pathogens in particular samples, for answering public health questions, such as the relationship of presence and absence of pathogens in their hosts respect to environmental conditions.
Alkishe et al. (2024) Broad-scale ecological niches of pathogens vectored by the ticks Ixodes scapularis and Amblyomma americanum in North America. PeerJ 12:e17944 https://doi.org/10.7717/peerj.17944
Efficacy and safety of etrolizumab in the treatment of inflammatory bowel disease: a meta-analysis
Background To explore the efficacy and safety of etrolizumab in treating inflammatory bowel disease (IBD) through meta-analysis. Method A comprehensive exploration encompassed randomized controlled trials examining the efficacy of etrolizumab in treating IBD across PubMed, Embase, Cochrane library, and Web of Science, with a search deadline of 1 December 2023. Quality assessment leaned on the Cochrane manual’s risk-of-bias evaluation, while Stata 15 undertook the data analysis. Result Five randomized controlled studies involving 1682 individuals were finally included, Meta-analysis results suggested that compared with placebo, etrolizumab could improve clinical response (RR = 1.26, 95% CI [1.04–1.51]), clinical remission (RR = 1.26, 95% CI [1.04–1.51]) in IBD patients. Endoscopic alleviate (RR = 2.10, 95% CI [1.56–2.82]), endoscopic improvement (RR = 2.10, 95% CI [1.56–2.82]), endoscopic remission (RR = 2.10, 95% CI [1.56–2.82]), Endoscopic improvement (RR = 1.56, 95% CI [1.30–1.89]), histological remission (RR = 1.62, 95% CI [1.26–2.08]), and did not increase any adverse events (RR = 0.95, 95% CI [0.90–1.01]) and serious adverse events (RR = 0.94, 95% CI [0.68–1.31]). Conclusion According to our current study, etrolizumab is a promising drug in IBD.
Dai et al. (2024) Efficacy and safety of etrolizumab in the treatment of inflammatory bowel disease: a meta-analysis. PeerJ 12:e17945 https://doi.org/10.7717/peerj.17945
Test-retest reliability of a single isometric mid-thigh pull protocol to assess peak force and strength-endurance
The purpose of this study was to examine the test-retest reliability of strength-endurance protocols using isometric mid-thigh pull (IMTP). Twenty-eight participants (23.2 ± 4.9 years) completed two protocols across four testing sessions. Protocol one consisted of 10 maximal IMTP tests lasting 5 seconds each with 10 seconds rest between. Protocol two consisted of a prolonged 60 second maximal IMTP. Data from protocol 1 was analysed in two ways; (a) use of the highest peak value from the first three IMTP efforts, and the lowest peak value from the final three IMTP efforts, and (b) use of the mean peak force from the first three IMTP efforts and mean peak force from the final three IMTP efforts. Data from protocol two used the highest and lowest peak values in the first- and final-15 seconds. Analyses revealed excellent reliability for peak force across all four testing sessions (ICC = 0.94), as well as good test-retest reliability for strength-endurance for protocol 1 (a; ICC = 0.81, b; ICC = 0.79). Test-retest reliability for protocol 2 was poor (ICC = 0.305). Bland-Altman bias values were smaller for protocol 1(a = −8.8 Nm, b = 21.7 Nm) compared to protocol 2 = (119.3 Nm). Our data suggest that 10 maximal IMTP tests performed as described herein is a reliable method for exercise professionals to assess both peak force and strength-endurance in a single, time-efficient protocol.
Grover et al. (2024) Test-retest reliability of a single isometric mid-thigh pull protocol to assess peak force and strength-endurance. PeerJ 12:e17951 https://doi.org/10.7717/peerj.17951
Unveiling the urban colonization of the Asian water monitor (Varanus salvator) across its distribution range using citizen science
Background This study aims to investigate the urban colonization of the Asian water monitor (Varanus salvator) across its entire range of distribution, addressing the paucity of research on this species in urban ecosystems. The research spans the geographic range of the Asian water monitor, focusing on urbanized areas where the species accumulates more observations (Bangkok, Colombo, Jakarta, Kuala Lumpur and Singapore). Methods We conducted a systematic review to comprehensively assess the current knowledge of the species’ presence in cities. Additionally, citizen science data from repositories like GBIF (Global Biodiversity Information facility ) were utilized to analyze the distribution patterns of V. salvator in urban environments. To elucidate urban distribution and correct collection biases, observations were weighted by sampling effort, using as a proxy all squamate occurrences available from 2010–2023, including V. salvator. Results Despite the widespread presence of the Asian water monitor in numerous cities within its distribution range, the available studies on the topic appear to be scarce. Existing research primarily consists of descriptive reports on diet and behavior. Our findings indicate that V. salvator predominantly colonizes green patches in urban areas, such as parks and small gardens. Larger cities exhibit higher records, potentially due to both permanent populations and increased citizen science reporting. Conclusions The Asian water monitor, as the largest lizard with established populations in cities, remains scarcely studied on a broader scale. However, the urban design of each city seems relevant to understand the distribution patterns within each context. Our study highlights the need for further research to explore the ecological and human dimensions associated with the species’ presence in urban environments.
Luna et al. (2024) Unveiling the urban colonization of the Asian water monitor (Varanus salvator) across its distribution range using citizen science. PeerJ 12:e17357 https://doi.org/10.7717/peerj.17357
Clinical and dosimetric correlation in terms of treatment response, bladder and rectal toxicities in cervical cancer patients treated with cobalt 60 high dose rate brachytherapy
Background High dose rate (HDR) image-guided brachytherapy with Cobalt-60 isotope is a relatively recent approach. The aim of the study is to evaluate the clinical and dosimetric parameters in terms of tumour response, bladder, and rectal toxicity in patients undergoing Co-60 HDR brachytherapy. Materials and Method All patients were initially treated with chemoradiation (CT-RT) at our center or other referral centers with external beam radiation therapy (EBRT) for a dose of 45 Gy–60 Gy at 1.8-2Gy/fraction (including nodal boost) with concomitant chemotherapy with either cisplatin or carboplatin. Patients were then scheduled for brachytherapy within 1 week after completion of CT-RT and are assessed by local examination. Depending on local examination parameters at the time of brachytherapy they were eligible either for intracavitary brachytherapy (ICBT) or interstitial brachytherapy (ISBT). Results The complete response (CR) observed in stage I, II, III, IVA were 60%, 79.4%, 86% and 76.2% respectively. Complete response was seen in patients with mean EQD2 of 78.67 Gy10, 83.33 Gy10, 84.23 Gy10, 85.63 Gy10 in stages I, II, III, IVA respectively. 79.2% of cisplatin-treated patients and 87.5% of carboplatin-treated patients had a complete response indicating that patients treated with either chemotherapy had similar response rates. Conclusions According to results obtained from the study we conclude by saying that higher rates of complete response to treatment in cervical cancer is seen in patients with shorter overall treatment time (OTT), shorter interval between end of definitive CT-RT and beginning of brachytherapy and squamous cell histology. The study also noted the trend of increasing mean EQD2 to tumor with increasing stage for achieving complete response. Higher acute bladder and rectal toxicity is seen in patients who received EQD2 of ¿70-90Gy3 and ¿70Gy3 respectively. The study findings suggest that the clinical outcomes and the toxicities are clinically comparable with other radioisotope based HDR brachytherapy treatment.
Makkapati et al. (2024) Clinical and dosimetric correlation in terms of treatment response, bladder and rectal toxicities in cervical cancer patients treated with cobalt 60 high dose rate brachytherapy. PeerJ 12:e17759 https://doi.org/10.7717/peerj.17759