title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=140 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Geometrical determinants of cerebral artery fenestration for cerebral infarction link: https://peerj.com/articles/18774 last-modified: 2025-01-21 description: PurposeFew data are available on the causality of cerebral artery fenestration (CAF) triggering cerebral infarction (CI) and this study aims to identify representative morphological features that can indicate risks.MethodsA cohort comprising 89 patients diagnosed with CAF were enrolled from a total of 9,986 cranial MR angiographies. These patients were categorized into Infarction Group (n = 55) and Control Group (n = 34) according to infarction events. These two groups are divided into two subgroups depending on fenestration location (basilar artery or other cerebravascular location), respectively, i.e., BA Infarction Group (n = 37), BA Control Group (n = 23), Non_BA Infarction Group (n = 18), Non_BA Control Group (n = 11). This study firstly defined 12 indices to quantify the morphological characteristics of fenestration per se and its connecting arteries. The data were evaluated using either the independent sample t-test or the Mann–Whitney U test. Conducting univariate and multivariate logistic regression analyses to ascertain potential independent predictors of CI.ResultsThe initiation angle φ1 and confluence angle φ2 at the fenestration in the Infarction Group are both smaller compared to the Control Group, but only the Infarction Group and BA Infarction Group have significant difference (p < 0.05). The maximum left fenestration axis (fAL) and the left tortuosity index (TIL) were greater in the Infarction Group for CAFs than those in the Control Group (p < 0.05). In contrast, the maximum right fenestration axis (fAR) and the right tortuosity index (TIR) were smaller than those in Control Group (p < 0.05). The logistic regression analysis revealed that φ2 (AUC = 0.68, p = 0.02), fAL (AUC = 0.72, p < 0.01), and fAR (AUC = 0.70, p < 0.01) serve as independent risk factors influencing the occurrence of CI. The regression predictive model achieved an AUC of 0.83, enabling accurate classification of 77.5% of cases, indicating a robust predictive performance of the model.ConclusionMorphological results demonstrated a left-leaning type of fenestration with more narrow fenestration terminals indicating a higher risk of CI occurrence. Furthermore, the regression predictive model established in this study demonstrates a good predictive performance, enabling early prediction of CI occurrence in fenestrated patients and facilitating early diagnosis of CI. creator: Yuqian Mei creator: Xiaoqin Chen creator: Yao Zhang creator: Yanling Wang creator: Bo Wu creator: Mingcheng Hu creator: Quan Bao uri: https://doi.org/10.7717/peerj.18774 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Mei et al. title: Development of metastasis and survival prediction model of luminal and non-luminal breast cancer with weakly supervised learning based on pathomics link: https://peerj.com/articles/18780 last-modified: 2025-01-21 description: ObjectiveBreast cancer stands as the most prevalent form of cancer among women globally. This heterogeneous disease exhibits varying clinical behaviors. The stratification of breast cancer patients into risk groups, determined by their metastasis and survival outcomes, is pivotal for tailoring personalized treatments and therapeutic interventions. The pathological sections of radical specimens encompass a diverse range of histological information pertinent to the metastasis and survival of patients. In this study, our objective is to develop a deep learning model utilizing pathological images to predict the metastasis and survival outcomes for breast cancer patients.MethodsThis study utilized pathological sections from 204 radical mastectomy specimens obtained between January 2013 and December 2014 at the Second Affiliated Hospital of the Medical College of Zhejiang University. The 204 pathological slices were scanned and transformed into whole slide imaging (WSI), with manual labeling of all tumor areas. The WSI was then partitioned into smaller tiles measuring 512 × 512 pixels. Three networks, namely Densely Connected Convolutional Network 121 (DenseNet121), Residual Network (ResNet50), and Inception_v3, were assessed. Subsequently, we combined patch-level predictions, probability histograms, and Term Frequency-Inverse Document Frequency (TF-IDF) features to create comprehensive participants representations. These features served as the foundational input for developing a machine learning algorithm for metastasis analysis and a Cox regression model for survival analysis.ResultOur results show that the Inception_v3 model shows a particularly robust patch recognition ability for estrogen receptor (ER) recognition. Our pathological model shows high accuracy in predicting tumor regions. The train area under the curve (AUC) of the Inception_v3 model based on supervised learning is 0.975, which is higher than the model established by weakly supervised learning. But the AUC of the metastasis prediction in training and testing sets is higher than value based on supervised learning. Furthermore, the C-index of the survival prediction model is 0.710 in the testing sets, which is also better than the value by supervised learning.ConclusionOur study demonstrates the significant potential of deep learning models in predicting breast cancer metastasis and prognosis, with the pathomic model showing high accuracy in identifying tumor areas and ER status. The integration of clinical features and pathomics signature into a nomogram further provides a valuable tool for clinicians to make individualized treatment decisions. creator: Hui Liu creator: Linlin Ying creator: Xing Song creator: Xueping Xiang creator: Shumei Wei uri: https://doi.org/10.7717/peerj.18780 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Liu et al. title: Melatonin attenuates MPP+-induced autophagy via heat shock protein in the Parkinson’s disease mouse model link: https://peerj.com/articles/18788 last-modified: 2025-01-21 description: BackgroundThis study investigates the protective properties of melatonin in an in vivo Parkinson’s disease (PD) model, focusing on the underlying mechanisms involving heat shock proteins (HSPs).MethodsTwelve adult male C57BL/6 mice were randomly divided into four groups (normal control, melatonin control, Parkinson’s model, and melatonin treatment; n = 3 per group) and housed in a single cage. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected intraperitoneally in the Parkinson’s model and treatment groups to establish a subacute PD model, while controls received saline. Limb motor ability was assessed 1 h after the final injection using behavioral tests, including the open field test to evaluate central zone entries and average movement. Dopamine transporter (DAT) expression in the striatum was analyzed by immunohistochemistry, and Western blot was used to measure autophagy proteins and HSP70 levels.ResultsThe PD mouse model was successfully established through MPTP stimulation. Compared to the normal control group, the model group showed a significant reduction in the frequency of entering the central zone and average movement. The number of DAT-positive cells in the brain also decreased significantly. The expression levels of HSP70 and CDK5 were significantly lower, while the expression levels of LC3 II /LC3I and p62 increased significantly. In the MT treatment group, both the frequency of entering the central zone and the average movement were significantly higher compared to the model group. DAT-positive cells in the midbrain also increased significantly. The expression levels of HSP70 and CDK5 were significantly elevated, while the expression levels of LC3 II /LC3I and p62 protein were significantly decreased.ConclusionMelatonin exerts a protective effect against MPP+-induced damage to dopaminergic neurons, presumably by upregulating HSP70, which inhibits neuronal autophagy. creator: Yinli Guo creator: Chengbo Liu uri: https://doi.org/10.7717/peerj.18788 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Guo and Liu title: Controlled temperature contrasts of three native and one highly invasive annual plant species in California link: https://peerj.com/articles/18794 last-modified: 2025-01-21 description: Plant responses to changes in temperature can be a key factor in predicting the presence and managing invasive plant species while conserving resident native plant species in dryland ecosystems. Climate can influence germination, establishment, and seedling biomass of both native and invasive plant species. We tested the hypothesis that common and widely distributed native and an invasive plant species in dryland ecosystems in California respond differently to increasing temperatures. To test this, we examined the effects of temperature variation on germination, establishment, and per capita seedling biomass of three native and one invasive plant species (Bromus rubens) in independent 6 week growth trial experiments in a controlled greenhouse. Higher relative temperatures reduced the germination and establishment of the tested invasive species and two tested native species, however, per capita biomass was not significantly affected. Specifically, germination and establishment of the invasive species B. rubens and the native species Phacelia tanacetifolia was significantly reduced. This invasive species can often outcompete natives, but increasing temperature could potentially shift the balance between the germination and establishment of natives. A warming climate will likely have negative impacts on native annual plant species in California tested here because increasing temperatures can co-occur with drought. This study shows that our tested native annual plant species tested here have some resilience to relatively significant increases in temperature, and this can favor at least one native species relative to at least one highly noxious invasive plant species. creator: Mario Zuliani creator: Stephanie Haas-Desmarais creator: Laura Brussa creator: Jessica Cunsolo creator: Angela Zuliani creator: Christopher J. Lortie uri: https://doi.org/10.7717/peerj.18794 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Zuliani et al. title: Turkish validation of a resilience scale from older people’s perspectives: resilience scale for older adults link: https://peerj.com/articles/18837 last-modified: 2025-01-21 description: BackgroundAs the global population ages and life expectancy increases, older adults encounter challenges like chronic illnesses and losing loved ones; resilience is crucial for adapting to these difficulties. This study aims to culturally and linguistically adapt the psychological resilience scale designed for older adults to the Turkish context.MethodsThis methodological study included 566 individuals aged 65 and older. All participants completed the Resilience Scale for Older Adults, the Perceived Stress Scale, the Geriatric Depression Scale, and the Quality of Life in Older Adults Scale—Short Form. Construct validity was assessed through confirmatory and exploratory factor analyses, while convergent and discriminant validity were evaluated through the correlation of the scales. Reliability was determined using internal consistency and the split-half method.ResultsThe scale retains its original structure with 33 items and four sub-dimensions (Intrapersonal, Interpersonal, Spiritual, and Experiential). The content validity index of the scale is 0.98, with item loadings ranging from 0.406 to 0.947, according to exploratory factor analysis. Confirmatory factor analysis indicates good fit indices. Convergent validity is supported by a strong positive correlation (r = 0.657, p < 0.001) between the Resilience Scale for Older Adults and the Quality of Life in Older Adults Scale—Short Form. Reliability measures include a Cronbach’s alpha internal consistency coefficient of 0.93 and a Guttman split-half reliability coefficient of 0.723.ConclusionThe results show that the Turkish version of the Resilience Scale for Older Adults is a valid and reliable measurement tool. creator: Seher Palanbek Yavaş creator: Caner Baysan uri: https://doi.org/10.7717/peerj.18837 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Palanbek Yavaş and Baysan title: SSR marker-based genetic diversity and structure analyses of Camellia nitidissima var. phaeopubisperma from different populations link: https://peerj.com/articles/18845 last-modified: 2025-01-21 description: BackgroundCamellia nitidissima var. phaeopubisperma is a variety in the section Chrysantha of the genus Camellia of the family Theaceae which is native to Fangchenggang, Guangxi, China. To date, the genetic diversity and structure of this variety remains to be understood.MethodsIn the present study, eight simple sequence repeat (SSR) molecular markers previously screened were used to analyze the genetic diversity and structure of C. nitidissima var. phaeopubisperma natural populations from 14 growing areas in China, so as to determine the influence of environmental changes on genetic variations and provide the basis for introduction and selection of suitable growing sites of that variety.ResultsOur results show that, for the eight SSR loci, the observed numbers of alleles per locus (Na) and the effective numbers of alleles per locus (Ne) were nine and 3.206, respectively on average, and the Ne was lower than the Na for all loci; the observed heterozygosity (Ho) was lower than the expected heterozygosity (He). For all the eight loci, the fixation index (F) was greater than 0, and the intra-population inbreeding coefficient (Fis) for seven loci was positive. Three loci were moderately polymorphic (0.25 < polymorphism information content (PIC) <0.5), and five loci were highly polymorphic (PIC > 0.5); all eight loci had a moderate genetic differentiation level (0.05 < genetic differentiation coefficient (Fst) <0.25). As shown by the genetic diversity analysis, the He was bigger than the Ho for 10 populations, indicating the presence of a certain degree of intra-population inbreeding. The F had a negative value for four populations, suggesting that excessive random mating was present within each of them. Results of the analysis of molecular variance show that 19% of the total variation was attributed to among-individuals and 78% of the total variation originated from within-individuals. The adjusted Fst (F’st) was 0.073, indicative of a moderate level of genetic differentiation among the populations. The value of gene flow was greater than 1 (7.367), suggesting that genetic differentiation among populations was not caused by genetic drift. Results of the STRUCTURE analysis show that all the samples tested could be clustered into five ancestor groups. Results of the Unweighted Pair Group Method using Arithmetic Averages (UPGMA) clustering analyses show that the 84 plant samples could be divided into three clusters and natural populations from the 14 growing areas could be divided into two clusters. Clustering results of the populations were not affected by geographic distances, and gene flow occurred frequently among the populations, suggesting that the genetic variation among the natural populations of C. nitidissima var. phaeopubisperma from 14 growing areas was not influenced by environmental changes of these areas but mainly derived from the genetic variation present in pre-introduction populations. creator: Yang-Jiao Xie creator: Meng-Xue Su creator: Hui Gao creator: Guo-Yue Yan creator: Shuang-Shuang Li creator: Jin-Mei Chen creator: Yan-Yuan Bai creator: Jia-Gang Deng uri: https://doi.org/10.7717/peerj.18845 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Xie et al. title: A nociceptor-specific RNAi screen in Drosophila larvae identifies RNA-binding proteins that regulate thermal nociception link: https://peerj.com/articles/18857 last-modified: 2025-01-21 description: Nociception is the process by which sensory neurons detect and encode potentially harmful environmental stimuli to generate behavioral responses. Nociceptor neurons exhibit plasticity in which their sensitivity to noxious stimuli and subsequent ability to drive behavior may be altered by environmental conditions, injury, infection, and inflammation. In some cases, nociceptor sensitization requires regulated changes in gene expression, and recent studies have indicated roles for post-transcriptional mechanisms in regulating these changes as an aspect of nociceptor plasticity. The larvae of Drosophila melanogaster have been developed as a powerful model for studying mechanisms of nociception, nociceptor plasticity, and nociceptor development. Diverse RNA-binding proteins regulate the development and morphology of larval nociceptors, implying important roles for post-transcriptional regulation of gene expression in these neurons, but the importance of these mechanisms for nociceptive behavior has not been investigated systematically. In this study, we conducted a nociceptor-specific RNAi screen of 112 candidate RNA-binding protein genes to identify those that are required for normal sensitivity to noxious thermal stimuli. The screen and subsequent validation experiments identified nine candidate genes (eIF2α, eIF4A, eIF4AIII, eIF4G2, mbl, SC35, snf, Larp4B and CG10445) that produce defects in nociceptive response latency when knocked down in larval nociceptors. Some of the genes identified have well-understood roles in the regulation of translation initiation and regulation of nociceptor sensitization in vertebrate and invertebrate animal models, suggesting an evolutionarily conserved role for these mechanisms in regulating nociceptor sensitivity. Other screen isolates have previously described roles in regulating nociceptor morphology and mRNA processing, but less clear roles in regulating nociceptor function. Further studies will be necessary to identify the mechanisms by which the identified RNA-binding proteins regulate sensory neuron function and the identities of the mRNAs that they target. creator: Amber Dyson creator: Gita Gajjar creator: Katherine C. Hoffman creator: Dakota Lewis creator: Sara Palega creator: Erik Rangel Silva creator: James Auwn creator: Andrew Bellemer uri: https://doi.org/10.7717/peerj.18857 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Dyson et al. title: Photogrammetric determination of movement speed of invasive Indo-Pacific lionfish in the Florida Keys link: https://peerj.com/articles/18474 last-modified: 2025-01-20 description: As a key determinant of how efficiently lionfish (Pterois sp.) locate and capture prey, swimming speed plays a crucial role in shaping the predator-prey interactions and broader ecological dynamics within the invaded ecosystems. Swimming speed on a small temporal and spatial scale is difficult to measure because of the need for precise measurements of both distance and duration of the behavior. Using photogrammetry by way of stereo-camera setups is ideal for analyzing the minutiae of lionfish behaviors because it can include the benefits of remote video traps coupled with precise measurements of movements in three-dimensional space and time. The primary objective of this study was to identify and characterize lionfish behavior associated with different movement speeds, and then to quantify small-scale swimming speeds of lionfish associated with those behaviors. Swimming speeds were classified under three different observed behaviors: relaxed swimming, traverse swimming, and striking at prey. The differences between these behaviors were primarily distinguished based on body and fin positioning, as well as the apparent intent of the motion if any was evident. The mean lionfish swimming speed from stereoscopic camera footage was 44.75 mm s−1 for relaxed swimming, 138.99 mm s−1 for traverse swimming, and 625.44 mm s−1 for striking at prey. Swimming speed can be used to quantify how much habitat area a lionfish may cover in a day, and therefore the amount of prey that may be encountered by a predator. Lionfish feeding success under different environmental conditions could be an important factor in understanding their survival and growth in areas where they are found. creator: Neal Kolonay creator: Cassandra N. Glaspie uri: https://doi.org/10.7717/peerj.18474 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Kolonay and Glaspie al. title: Genetic determinants of COVID-19 severity and mortality: ACE1 Alu 287 bp polymorphism and ACE1, ACE2, TMPRSS2 expression in hospitalized patients link: https://peerj.com/articles/18508 last-modified: 2025-01-20 description: BackgroundThe angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are central human molecules in the SARS-CoV-2 virus-host interaction. Evidence indicates that ACE1 may influence ACE2 expression. This study aims to determine whether ACE1, ACE2, and TMPRSS2 mRNA expression levels, along with the ACE1 Alu 287 bp polymorphism (rs4646994), contribute to the severity and mortality of COVID-19.MethodsSwabs were collected in two Brazilian cities in 2020: Belo Horizonte (n = 134) and Rio de Janeiro (n = 41). A swab of mild patients in Rio de Janeiro who were not hospitalized (n = 172) was also collected. All analyzed biological material was obtained from residual diagnostic samples in 2020, prior to the emergence of SARS-CoV-2 variants of concern. ACE1, ACE2, TMPRSS2, and B2M (reference gene) expression levels were evaluated in 40 cycles of quantitative PCR. ACE1 Alu 287 bp polymorphism was genotyped using the FastStart Universal SYBR Green Master kit.ResultsThe median age differed between clinical sites (p = 0.016), but no difference in median days of hospitalization was observed (p = 0.329). Age was associated with severity (p = 0.014) and mortality (p = 0.014) in the Belo Horizonte cohort. No alteration in ACE1, ACE2 and TMPRSS2 expression was associated with severity or mortality. ACE1 polymorphism rs4646994 did not influence the likelihood of either outcome. A meta-analysis including available data from the literature showed significant effects: the D-allele conferred risk (OR = 1.39; 95% CI [1.12–1.72]). creator: João Locke Ferreira de Araújo creator: Átila Duque Rossi creator: Jessica Maciel de Almeida creator: Hugo José Alves creator: Isabela de Carvalho Leitão creator: Renata Eliane de Ávila creator: Anna Carla Pinto Castiñeiras creator: Jéssica da Silva Oliveira creator: Rafael Mello Galliez creator: Marlon Daniel Lima Tonini creator: Débora Souza Faffe creator: Shana Priscila Coutinho Barroso Barroso creator: Gustavo Gomes Resende creator: Cássia Cristina Alves Gonçalves creator: Terezinha Marta Pereira Pinto Castiñeiras creator: Amilcar Tanuri creator: Mauro Martins Teixeira creator: Renato Santana Aguiar creator: Cynthia Chester Cardoso creator: Renan Pedra de Souza uri: https://doi.org/10.7717/peerj.18508 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 de Araújo et al. title: Targeted correction of megabase-scale CNTN6 duplication in induced pluripotent stem cells and impacts on gene expression link: https://peerj.com/articles/18567 last-modified: 2025-01-20 description: Copy number variations of the human CNTN6 gene, resulting from megabase-scale microdeletions or microduplications in the 3p26.3 region, are frequently implicated in neurodevelopmental disorders such as intellectual disability and developmental delay. However, duplication of the full-length human CNTN6 gene presents with variable penetrance, resulting in phenotypes that range from neurodevelopmental disorders to no visible pathologies, even within the same family. Previously, we obtained a set of induced pluripotent stem cell lines derived from a patient with a CNTN6 gene duplication and from two healthy donors. Our findings demonstrated that CNTN6 expression in neurons carrying the duplication was significantly reduced. Additionally, the expression from the CNTN6 duplicated allele was markedly lower compared to the wild-type allele. Here, we first introduce a system for correcting megabase-scale duplications in induced pluripotent stem cells and secondly analyze the impact of this correction on CNTN6 gene expression. We showed that the deletion of one copy of the CNTN6 duplication did not affect the expression levels of the remaining allele in the neuronal cells. creator: Maria Gridina creator: Polina Orlova creator: Oleg Serov uri: https://doi.org/10.7717/peerj.18567 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Gridina et al.