Identification of sterile a-motif domain-containing 9-like as a potential biomarker in patients with cutaneous melanoma
Skin cutaneous melanoma (SKCM) is one of the most aggressive malignancies, accounting for approximately 75% of skin cancer-related fatalities annually. Sterile a-motif domain-containing 9-like (SAMD9L) has been found to regulate cell proliferation and suppress the neoplastic phenotype, but its specific role in SKCM remains unknown. To investigate the cancer-associated immunology of SKCM and the role of SAMD9L in tumor progression, we conducted an integrative bioinformatics analysis that revealed elevated expression levels of SAMD9L in SKCM. ROC curves and survival analyses confirmed the considerable diagnostic and prognostic abilities of SAMD9L. Moreover, a real-world cohort of 35 SKCM patients from the First Affiliated Hospital of Soochow University showed that higher expression levels of SAMD9L were associated with better prognosis. We performed validation experiments, including cell culture, generation of lentiviral-transfected SKCM cell lines, cell proliferation assay, and transwell assay, which demonstrated that down-regulation of SAMD9L significantly promoted proliferation and migration capacities of SKCM cells. Additionally, SAMD9L expression was found to be strongly linked to immune infiltration. Our results revealed a positive correlation between SAMD9L and XAF1 expression, suggesting that SAMD9L may serve as a prospective prognostic indicator of SKCM with co-expressed XAF1 gene. In summary, our findings indicate that SAMD9L may serve as a promising prognostic and therapeutic biomarker and play a critical role in tumor-immune interactions in SKCM.
Ye et al. (2023) Identification of sterile a-motif domain-containing 9-like as a potential biomarker in patients with cutaneous melanoma. PeerJ 11:e15634 https://doi.org/10.7717/peerj.15634
The mediating role of attention deficit in relationship between insomnia and social cognition tasks among nurses in Saudi Arabia: A cross-sectional study
Purpose Insomnia-related affective functional disorder may negatively affect social cognition such as empathy, altruism, and attitude toward providing care. No previous studies have ever investigated the mediating role of attention deficit in the relationship between insomnia and social cognition. Methods A cross-sectional survey was carried out among 664 nurses (Mage = 33.03 years; SD ± 6.93 years) from December 2020 to September 2021. They completed the Scale of Attitude towards the Patient (SAtP), the Athens Insomnia Scale (AIS), a single-item numeric rating scale assessing the increasing severity of attention complaints, and questions relating to socio-demographic information. The analysis was carried out by examining the mediating role of attention deficit in the relationship between insomnia and social cognition. Results The prevalence of insomnia symptoms was high (52% insomnia using the AIS). Insomnia was significantly correlated with attention problems (b = 0.18, standard error (SE) = 0.02, p < 0.001). Attention problems were significantly negatively correlated with nurses’ attitudes towards patients (b = −0.56, SE = 0.08, p < 0.001), respect for autonomy (b = −0.18, SE = 0.03, p < 0.001), holism (b = −0.14, SE = 0.03, p < 0.001), empathy (b = −0.15, SE = 0.03, p < 0.001), and altruism (b = −0.10, SE = 0.02, p < 0.001). Attention problems indirectly mediated the effect of insomnia on attitudes toward patients (99% CI = −0.10 [−0.16 to −0.05]), respect for autonomy (99% CI = −0.03 [−0.05 to −0.02]), holism (99% CI = −0.02 [−0.04 to −0.01]) empathy (99% CI = −0.03 [−0.04 to −0.01]), and altruism (99% CI = −0.02 [−0.03 to −0.01]). Conclusion Nurses with insomnia-related attention problems are likely to have poor explicit social cognition such as attitude toward patients, altruism, empathy, respect for autonomy, and holism.
Manzar et al. (2023) The mediating role of attention deficit in relationship between insomnia and social cognition tasks among nurses in Saudi Arabia: A cross-sectional study. PeerJ 11:e15508 https://doi.org/10.7717/peerj.15508
Functionalized nanoparticles crossing the brain–blood barrier to target glioma cells
Glioma is the most common tumor of the central nervous system (CNS), with a 5-year survival rate of <35%. Drug therapy, such as chemotherapeutic and immunotherapeutic agents, remains one of the main treatment modalities for glioma, including temozolomide, doxorubicin, bortezomib, cabazitaxel, dihydroartemisinin, immune checkpoint inhibitors, as well as other approaches such as siRNA, ferroptosis induction, etc. However, the filter function of the blood-brain barrier (BBB) reduces the amount of drugs needed to effectively target CNS tumors, making it one of the main reasons for poor drug efficacies in glioma. Thus, finding a suitable drug delivery platform that can cross the BBB, increase drug aggregation and retainment in tumoral areas and avoid accumulation in non-targeted areas remains an unsolved challenge in glioma drug therapy. An ideal drug delivery system for glioma therapy should have the following features: (1) prolonged drug life in circulation and effective penetration through the BBB; (2) adequate accumulation within the tumor (3) controlled-drug release modulation; (4) good clearance from the body without significant toxicity and immunogenicity, etc. In this regard, due to their unique structural features, nanocarriers can effectively span the BBB and target glioma cells through surface functionalization, providing a new and effective strategy for drug delivery. In this article, we discuss the characteristics and pathways of different nanocarriers for crossing the BBB and targeting glioma by listing different materials for drug delivery platforms, including lipid materials, polymers, nanocrystals, inorganic nanomaterials, etc.
Wu et al. (2023) Functionalized nanoparticles crossing the brain–blood barrier to target glioma cells. PeerJ 11:e15571 https://doi.org/10.7717/peerj.15571
Attitudes of medical students in Khartoum, Sudan towards the doctor-patient relationship: a cross-sectional study
Background/Objectives The doctor-patient relationship is essential to the delivery of high-quality medical care. A strong doctor-patient relationship that improves patient outcomes and satisfaction depends on effective communication. The purpose of this study was to assess medical students’ attitudes toward the doctor-patient relationship during their clinical years at the University of Khartoum. We also looked at how gender and study year affected patient-centeredness. Participants/Setting The study was conducted on medical students in their clinical years from December 2020 to March 2021. Students were selected from years 3 to 6. A total of 353 medical students constituted the study sample. Design The cross-sectional study utilized the Patient Practitioner Orientation Scale (PPOS) for the measurement of student attitudes towards the doctor-patient relationship. PPOS scores are calculated as a mean score that ranges from 1 (indicating doctor or disease-centered inclinations) to 6 (indicating patient-centered or egalitarian inclinations). Medical students’ demographic data was collected, including their gender, age and study year. Results A total of 313 students completed the survey (response rate: 89%). The average total PPOS score and the scores for the caring and sharing subscales for the entire cohort were 4.08 ± 0.53, 4.43 ± 0.58, and 3.72 ± 0.72, respectively. Female gender was significantly associated with more patient-centered attitudes (p < 0.001). When compared to the start of their clinical curriculum, students’ attitudes were significantly more patient-centered by the conclusion of their studies (p < 0.001). Conclusion A satisfactory level of patient-centeredness was demonstrated by medical students at the University of Khartoum, and gender had an impact on this quality. Additional consideration should be given to the finding that students’ orientations were more patient-centered in the caring dimension and less so in the sharing one. Once addressed, improvements in that area could create an environment that enhances attitudes among students in the sharing domain, with great potential gains to patients.
Haiba et al. (2023) Attitudes of medical students in Khartoum, Sudan towards the doctor-patient relationship: a cross-sectional study. PeerJ 11:e15434 https://doi.org/10.7717/peerj.15434
Measuring blood glucose before or after lumbar puncture
Background The ratio of cerebrospinal fluid (CSF) to peripheral blood glucose at the same period is an important index for diagnosing and monitoring the efficacy of central nervous system infection, especially bacterial meningitis. Some guidelines refer that blood glucose measurement should be carried out before lumbar puncture. The main reason is to avoid possible effect of stress response induced by lumbar puncture on the level of blood glucose. However, there is no consensus on whether it should be followed in actual clinical work, since up to now no research work having been published on whether lumbar puncture will induce the changes on blood glucose. Our study aimed to investigate the changes of peripheral blood glucose before and after lumbar puncture. Methods In order to clarify the influence of timing of peripheral blood glucose measurement at the same period of lumbar puncture, a prospective study was conducted including children with an age range from 2 months to 12 years old in the neurology department of a medical center. For those children who need lumbar puncture due to their illness, their blood glucose was measured within 5 min before and after lumbar puncture, respectively. The blood glucose level and the ratio of CSF to blood glucose before and after lumbar puncture were compared. Meanwhile, the patients were divided into different groups according to the factors of sex, age and sedation or not for further comparison. All statistical analyses of the data were performed using SPSS version 26.0 for Windows. Results In total, 101 children who needed lumbar puncture during hospitalization from January 1, 2021, to October 1, 2021, were recruited with 65 male and 36 female respectively. There was no significant difference on the level of blood glucose, CSF to blood glucose ratio before and after lumbar puncture among the children (p > 0.05). No differences were observed within different groups (sex, age, sedation or not) either. Conclusion It is unnecessary to emphasize blood glucose measurement should be carried out before lumbar puncture, especially for pediatric patients. From the perspective of facilitating smoother cerebrospinal fluid puncture in children, blood glucose measurement after lumbar puncture might be a better choice.
Shi et al. (2023) Measuring blood glucose before or after lumbar puncture. PeerJ 11:e15544 https://doi.org/10.7717/peerj.15544
A histological analysis of coloration in the Peruvian mimic poison frog (Ranitomeya imitator)
Aposematism continues to be a phenomenon of central interest in evolutionary biology. The life history of the mimic poison frog, Ranitomeya imitator, relies heavily on aposematism. In order for aposematic signals to be effective, predators must be able to learn to avoid the associated phenotype. However, in R. imitator, aposematism is associated with four different color phenotypes that mimic a complex of congeneric species occurring across the mimic frog’s geographic range. Investigations of the underlying mechanics of color production in these frogs can provide insights into how and why these different morphs evolved. We used histological samples to examine divergence in the color production mechanisms used by R. imitator to produce effective aposematic signals across its geographic range. We measured the coverage of melanophores and xanthophores (the area covered by chromatophores divided by total area of the skin section) in each color morph. We find that morphs that produce orange skin exhibit a higher coverage of xanthophores and lower coverage of melanophores than those that produce yellow skin. In turn, morphs that produce yellow skin exhibit a higher coverage of xanthophores and lower coverage of melanophores than those that produce green skin. Generally, across the morphs, a high ratio of xanthophores to melanophores is associated with colors of brighter spectral reflectance. Together, our results contribute to the understanding of color production in amphibians and document divergence in the histology of a species that is subject to divergent selection associated with aposematism.
de Araujo Miles et al. (2023) A histological analysis of coloration in the Peruvian mimic poison frog (Ranitomeya imitator). PeerJ 11:e15533 https://doi.org/10.7717/peerj.15533
Comparative analysis of machine learning approaches for predicting respiratory virus infection and symptom severity
Respiratory diseases are among the major health problems causing a burden on hospitals. Diagnosis of infection and rapid prediction of severity without time-consuming clinical tests could be beneficial in preventing the spread and progression of the disease, especially in countries where health systems remain incapable. Personalized medicine studies involving statistics and computer technologies could help to address this need. In addition to individual studies, competitions are also held such as Dialogue for Reverse Engineering Assessment and Methods (DREAM) challenge which is a community-driven organization with a mission to research biology, bioinformatics, and biomedicine. One of these competitions was the Respiratory Viral DREAM Challenge, which aimed to develop early predictive biomarkers for respiratory virus infections. These efforts are promising, however, the prediction performance of the computational methods developed for detecting respiratory diseases still has room for improvement. In this study, we focused on improving the performance of predicting the infection and symptom severity of individuals infected with various respiratory viruses using gene expression data collected before and after exposure. The publicly available gene expression dataset in the Gene Expression Omnibus, named GSE73072, containing samples exposed to four respiratory viruses (H1N1, H3N2, human rhinovirus (HRV), and respiratory syncytial virus (RSV)) was used as input data. Various preprocessing methods and machine learning algorithms were implemented and compared to achieve the best prediction performance. The experimental results showed that the proposed approaches obtained a prediction performance of 0.9746 area under the precision-recall curve (AUPRC) for infection (i.e., shedding) prediction (SC-1), 0.9182 AUPRC for symptom class prediction (SC-2), and 0.6733 Pearson correlation for symptom score prediction (SC-3) by outperforming the best leaderboard scores of Respiratory Viral DREAM Challenge (a 4.48% improvement for SC-1, a 13.68% improvement for SC-2, and a 13.98% improvement for SC-3). Additionally, over-representation analysis (ORA), which is a statistical method for objectively determining whether certain genes are more prevalent in pre-defined sets such as pathways, was applied using the most significant genes selected by feature selection methods. The results show that pathways associated with the ‘adaptive immune system’ and ‘immune disease’ are strongly linked to pre-infection and symptom development. These findings contribute to our knowledge about predicting respiratory infections and are expected to facilitate the development of future studies that concentrate on predicting not only infections but also the associated symptoms.
Işık et al. (2023) Comparative analysis of machine learning approaches for predicting respiratory virus infection and symptom severity. PeerJ 11:e15552 https://doi.org/10.7717/peerj.15552
Influencing factors of cardiac valve calcification (CVC) in patients with chronic kidney disease and the impact of CVC on long-term prognosis: a single-center retrospective study
Objective To investigate the effect of cardiac valve calcification (CVC) on the prognosis of patients with chronic kidney disease (CKD). Methods A total of 343 CKD patients were retrospectively analyzed, and divided into two groups according to the presence or absence of cardiac valve calcification. All patients were followed until death, loss to follow-up, or the end point of the study (December 2021). Results The incidence of CVC among the 343 CKD patients was 29.7%, including 21 cases of mitral valve calcification, 63 cases of aortic valve calcification, and 18 cases of mitral valve combined with aortic valve calcification. The incidence of CVC in CKD stages 1–2 was 0.3%, 5.2% in CKD stages 3–4, and 24.2% in CKD stage 5 (P < 0.05). Advanced age, higher serum albumin, higher cystatin C and lower uric acid levels were all associated with a higher risk of CVC. After six years of follow-up, 77 patients (22.4%) died. The causes of death were cardiovascular and cerebrovascular diseases in 36 cases (46.7%), infection in 29 cases (37.7%), gastrointestinal bleeding in nine cases (11.7%), and “other” in the remaining three cases (3.9%). A Kaplan Meier survival analysis showed that the overall survival rate of patients with CVC was lower than that of patients without CVC. Conclusion The incidence of CVC, mainly aortic calcification, is high in patients with CKD. Advanced age, higher serum albumin and higher cystatin C levels were associated with a higher risk of CVC. Hyperuricemia was associated with a lower risk of CVC. The overall survival rate of patients with CVC was lower than that of patients without CVC.
Wang et al. (2023) Influencing factors of cardiac valve calcification (CVC) in patients with chronic kidney disease and the impact of CVC on long-term prognosis: a single-center retrospective study. PeerJ 11:e15569 https://doi.org/10.7717/peerj.15569
MK8617 inhibits M1 macrophage polarization and inflammation via the HIF-1α/GYS1/UDPG/P2Y14 pathway
Background Nonresolving inflammation is a major driver of disease and needs to be taken seriously. Hypoxia-inducible factor (HIF) is closely associated with inflammation. Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs), as stabilizers of HIF, have recently been reported to have the ability to block inflammation. We used MK8617, a novel HIF-PHI, to study its effect on macrophage inflammation and to explore its possible mechanisms. Methods Cell viability after MK8617 and lipopolysaccharide (LPS) addition was assessed by Cell Counting Kit-8 (CCK8) to find the appropriate drug concentration. MK8617 pretreated or unpretreated cells were then stimulated with LPS to induce macrophage polarization and inflammation. Inflammatory indicators in cells were assessed by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), western blot (WB) and immunofluorescence (IF). The level of uridine diphosphate glucose (UDPG) in the cell supernatant was measured by ELISA. Purinergic G protein-coupled receptor P2Y14, as well as hypoxia-inducible factor-1α (HIF-1α) and glycogen synthase 1 (GYS1) were detected by qRT-PCR and WB. After UDPG inhibition with glycogen phosphorylase inhibitor (GPI) or knockdown of HIF-1α and GYS1 with lentivirus, P2Y14 and inflammatory indexes of macrophages were detected by qRT-PCR and WB. Results MK8617 reduced LPS-induced release of pro-inflammatory factors as well as UDPG secretion and P2Y14 expression. UDPG upregulated P2Y14 and inflammatory indicators, while inhibition of UDPG suppressed LPS-induced inflammation. In addition, HIF-1α directly regulated GYS1, which encoded glycogen synthase, an enzyme that mediated the synthesis of glycogen by UDPG, thereby affecting UDPG secretion. Knockdown of HIF-1α and GYS1 disrupted the anti-inflammatory effect of MK8617. Conclusions Our study demonstrated the role of MK8617 in macrophage inflammation and revealed that its mechanism of action may be related to the HIF-1α/GYS1/UDPG/P2Y14 pathway, providing new therapeutic ideas for the study of inflammation.
Qian et al. (2023) MK8617 inhibits M1 macrophage polarization and inflammation via the HIF-1α/GYS1/UDPG/P2Y14 pathway. PeerJ 11:e15591 https://doi.org/10.7717/peerj.15591
miR-455-3p ameliorates pancreatic acinar cell injury by targeting Slc2a1
Objective With the number of patients with acute pancreatitis (AP) increasing year by year, it is pressing to explore new key genes and markers for the treatment of AP. miR-455-3p/solute carrier family 2 member 1 (Slc2a1) obtained through bioinformatics analysis may participate in the progression of AP. Materials and Methods The C57BL/6 mouse model of AP was constructed for subsequent studies. Through bioinformatics analysis, the differentially expressed genes related to AP were screened and hub genes were identified. A caerulein-induced AP animal model was constructed to detect the pathological changes of mouse pancreas by HE staining. The concentrations of amylase and lipase were measured. Primary mouse pancreatic acinar cells were isolated and subjected to microscopy to observe their morphology. The enzymatic activities of trypsin and amylase were detected. The secretion of inflammatory cytokines in mouse were measured with the ELISA kits of TNF-α, IL-6 and IL-1β to determine pancreatic acinar cell damage. A binding site between the Slc2a1 3′ UTR region and the miR-455-3p sequence was verified by dual-luciferase reporter assay. The expression of miR-455-3p was quantified by qRT-PCR, and Slc2a1 were detected by western blot. Results A total of five (Fyn, Gadd45a, Sdc1, Slc2a1, and Src) were identified by bioinformatics analysis, and miR-455-3p/Slc2a1 were further studied. HE staining results showed that the AP models were successfully established by caerulein induction. In mice with AP, the expression of miR-455-3p was reduced, while that of Slc2a1 was increased. In the caerulein-induced cell model, the expression of Slc2a1 was significantly reduced after intervention of miR-455-3p mimics, whereas increased after miR-455-3p inhibitor treatment. miR-455-3p decreased the secretion of inflammatory cytokines in the cell supernatant, reduced the activity of trypsin and amylase, and alleviated the cell damage induced by caerulein. In addition, Slc2a1 3’UTR region was bound by miR-455-3p, and its protein expression was also regulated. Conclusion miR-455-3p alleviated caerulein-induced mouse pancreatic acinar cell damage by regulating the expression of Slc2a1.
Zhan et al. (2023) miR-455-3p ameliorates pancreatic acinar cell injury by targeting Slc2a1. PeerJ 11:e15612 https://doi.org/10.7717/peerj.15612