bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome sequencing provides potential strategies for drug discovery and synthesis
Authors: Zhao Chunsheng , Zhang Ziwei , Sun Linlin , Bai Ronglu , Wang Lizhi , Chen Shilin
Published: September 2023

Medicinal plants are renowned for their abundant production of secondary metabolites, which exhibit notable pharmacological activities and great potential for drug development. The biosynthesis of secondary metabolites is highly intricate and influenced by various intrinsic and extrinsic factors, resulting in substantial species diversity and content variation. Consequently, precise regulation of secondary metabolite synthesis is of utmost importance. In recent years, genome sequencing has emerged as a valuable tool for investigating the synthesis and regulation of secondary metabolites in medicinal plants, facilitated by the widespread use of high-throughput sequencing technologies. This review highlights the latest advancements in genome sequencing within this field and presents several strategies for studying secondary metabolites. Specifically, the article elucidates how genome sequencing can unravel the pathways for secondary metabolite synthesis in medicinal plants, offering insights into the functions and regulatory mechanisms of participating enzymes. Comparative analyses of plant genomes allow identification of shared pathways of metabolite synthesis among species, thereby providing novel avenues for obtaining cost-effective biosynthetic intermediates. By examining individual genomic variations, genes or gene clusters associated with the synthesis of specific compounds can be discovered, indicating potential targets and directions for drug development and the exploration of alternative compound sources. Moreover, the advent of gene-editing technology has enabled the precise modifications of medicinal plant genomes. Optimization of specific secondary metabolite synthesis pathways becomes thus feasible, enabling the precise editing of target genes to regulate secondary metabolite production within cells. These findings serve as valuable references and lessons for future drug development endeavors, conservation of rare resources, and the exploration of new resources.
Secondary salvage intravenous chemotherapy for refractory/recurrent retinoblastoma: A study of 41 eyes
Authors: Kaliki Swathi , Gavara Suneetha , Patil Gaurav , Reddy Palkonda Vijay Anand
Published: September 2023

Purpose:

To determine the efficacy of secondary salvage intravenous chemotherapy (IVC) for refractory/recurrent retinoblastoma (RB).

Methods:

Retrospective, nonrandomized interventional case series of 41 eyes of 33 patients with RB

Results:

Of the 33 patients, mean age at the time of commencement of salvage IVC was 5 years (median, 5 years; range, 2 to 8 years). At presentation, RB in 41 eyes of 33 patients were classified by the International Classification of Retinoblastoma as Group B (n=7, 17%), Group C (n=3, 7%), Group D (n=16, 39%) and Group E (n=15, 37%). All patients received 6 cycles of IVC as primary treatment. The indication for secondary salvage IVC with focal treatment included recurrent solid tumor (n=36; 88%), subretinal seeds (n=22; 54%), or persistent solid tumor (n=2; 5%). Mean number of cycles of salvage IVC were 8 (median, 6; range, 6 to 18). Over a mean follow-up period of 43 months (median, 43 months; range, 12 to 96 months) after completion of salvage IVC, globe salvage was achieved in 22 (54%) eyes, 1 (3%) patient had histopathology-proven bone metastasis, and 1 (3%) patient died due to presumed metastasis.

Conclusion:

Secondary salvage IVC with appropriate focal treatment allows globe salvage in 54% eyes with refractory/recurrent RB and thus serves as an alternative to intra-arterial chemotherapy or enucleation.
Assessing and Identifying Improvements for Lung Cancer Screening in a Rural Population: A Human-Centered Design and Systems Approach
Authors: Golding Shaun A. , Hasson Rian M. , Kinney Linda M. , Kyung Ellie J. , Bardach Shoshana H. , Perry Amanda N. , Boardman Maureen B. , Halloran Sean R. , Youkilis Samuel L. , Fay Kayla A. , Bird Thomas L. , Bridges Connor J. , Schifferdecker Karen E.
Published: September 2023

Although lung cancer claims more lives than any other cancer in the United States, screening is severely underutilized, with <6% of eligible patients screened nationally in 2021 versus 76% for breast cancer and 67% for colorectal cancer. This article describes an effort to identify key reasons for the underutilization of lung cancer screening in a rural population and to develop interventions to address these barriers suitable for both a large health system and local community clinics. Data were generated from 26 stakeholder interviews (clinicians, clinical staff, and eligible patients), a review of key systems (Electronic Health Record and billing records), and feedback on the feasibility of several potential interventions by health care system staff. These data informed a human-centered design approach to identify possible interventions within a complex health care system by exposing gaps in care processes and electronic health record platforms that can lead patients to be overlooked for potentially life-saving screening. Deployed interventions included communication efforts focused on (1) increasing patient awareness, (2) improving physician patient identification, and (3) supporting patient management. Preliminary outcomes are discussed.
Life Experience of Chinese Pediatric Medulloblastoma Survivors: A Qualitative Study
Authors: Feng Jinzhi , He Qingqing , Sun Lin
Published: September 2023

BACKGROUND:With the improvement of technology and the advancement of medical treatment in recent decades, more and more pediatric medulloblastoma survivors reintegrate to the community. This study aimed to examine the experiences of pediatric medulloblastoma survivors.METHODS: A qualitative research was conducted. Twenty Chinese pediatric medulloblastoma survivors were interviewed. Interviews were recorded and transcribed. Colaizzi's analysis method was used to analyze data.RESULTS:There were 4 themes in this study: physical health issues, community reintegration challenges, overcoming psychological pressure, and multiple unmet needs.CONCLUSION: Pediatric medulloblastoma survivors face challenges in the physical, psychological, and social aspects of their health, along with multiple unmet healthcare needs. Nurses should comprehensively assess the survivor's needs from admission, plan for discharge, and provide regular follow-up care after discharge. Furthermore, nurses should collaborate with caregivers, clinicians, and schoolteachers to develop programs aimed at enhancing the quality of life for survivors. It is also important to explore the survival experiences of individuals in different regions.
A model including standardized weight improved predicting waiting list mortality in adolescent liver transplant candidates: A US national study
Authors: Shaheen Abdel Aziz , Martin Steven R. , Khorsheed Sahar , Abraldes Juan G.
Published: September 2023

The Model for End-Stage Liver Disease (MELD) score has been employed to identify adolescents eligible for liver transplantation since 2004. However, the optimal model for prioritizing adolescent candidates is uncertain. In our study, we aimed at evaluating the value of adding anthropometric variables to liver transplantation allocation models among adolescents. We conducted a retrospective cohort study using the data from the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research to identify adolescent patients registered on the liver transplant waiting list in the United States between January 1, 2003, and December 31, 2022. Adolescents (12–17 y) who were listed for their first liver transplantation were included. We evaluated the performance of different models including pediatric end-stage liver disease with Na and creatinine, MELD, and MELD 3.0. Furthermore, we evaluated whether adding anthropometric variables (z-score for weight and height) would improve the models’ performance for our primary outcome (mortality at 90 days after listing). We identified 1421 eligible adolescent patients. Adding a z-score of weight (MELD-TEEN) improved the performance and discrimination of the MELD score. The final model including weight z-score (MELD-TEEN) had better discriminative power compared to MELD 3.0 and pediatric end-stage liver disease with Na and creatinine in the overall cohort and in different age groups (ages 12–14 and 15–17). MELD-TEEN could improve the accuracy of allocation of liver transplants among adolescents by incorporating the weight z-score compared to MELD 3.0 and pediatric end-stage liver disease with Na and creatinine.
The efficacy of dexmedetomidine for septic shock: A meta-analysis of randomized controlled trials
Authors: Huang Xue , He Chunyan
Published: September 2023

Introduction:

The efficacy of dexmedetomidine was elusive for septic shock. This meta-analysis aimed to explore the efficacy of dexmedetomidine for septic shock.

Methods:

PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases have been searched through October 2022 and we included randomized controlled trials reporting the effect of dexmedetomidine in patients with septic shock.

Results:

Five randomized controlled trials were included in the meta-analysis. Compared with control group for septic shock, dexmedetomidine treatment was able to substantially decrease Sequential Organ Failure Assessment score (mean difference [MD] = ‐0.99; 95% confidence interval [CI] = ‐1.14 to ‐0.84; P < .00001) and duration of mechanical ventilation (MD = ‐0.90; 95% CI = ‐1.27 to ‐0.54; P < .00001), but showed no obvious influence on morality at 28 days (odds ratio = 0.79; 95% CI = 0.38 to 1.66; P = 054), hospital mortality (odds ratio = 0.66; 95% CI = 0.35 to 1.24; P = .20) or intensive care unit length of stay (MD = ‐1.47; 95% CI = ‐4.60 to 1.66; P = .36).

Conclusions:

Dexmedetomidine administration may help treat patients with septic shock.
The evolution of primary hyperparathyroidism publications and global productivity from past to present: A bibliometric analysis during 1980 to 2022
Authors: Göbüt Hüseyin , Bostanci Hasan
Published: September 2023

The aim of this study was to perform a descriptive analysis of scientific articles about primary hyperparathyroidism (PHPT) using bibliometric approaches. By analyzing the links between the various research components (authors, journals, institutions, countries) of the academic outputs, it was aimed to summarize the intellectual structure of PHPT, identify recent research trends, and determine the global productivity. Three thousand nine hundred fifty-four articles on PHPT published between 1980 and 2022 were pulled from the Web of Science database and analyzed using bibliometric approaches. Bibliometric network visualization maps were used to identify trending topics, citation analysis, and international collaborations. Spearman correlation coefficient was used for correlation analysis. The 3 most prolific authors are Bilezikian JP. (n = 87), Silverberg SJ. (n = 72) and Akerstrom G. (n = 57). The top 3 most productive institutions were Columbia University (n = 133), Udice French Research Universities (n = 127) and Uppsala University (n = 98). The top 3 most productive journals were Surgery (n = 216), Journal of Clinical Endocrinology and Metabolism (n = 201) and World Journal of Surgery (n = 148). The top 3 contributing countries to the PHPT literature were United States of America (n = 1062, 26.8%), Italy (346, 8.7%) and United Kingdom (274, 6.9%). The most studied topics from past to present are parathyroidectomy, hypercalcemia, parathyroid hormone/adenoma/glands, calcium/calcimimetics, scintigraphy/sestamibi, bone mineral density, ultrasound, vitamin D, osteoporosis, minimally invasive parathyroidectomy, brown tumor, nephrocalcinosis/nephrolithiasis, multiple endocrine neoplasia type 1, normocalcemia, pregnancy, imaging/preoperative imaging, parathyroid cancer/carcinoma, asymptomatic primary hyperparathyroidism, and cinacalcet. The trending topics in recent years were normocalcemic primary hyperparathyroidism, trabecular bone score, children, CDC73, microwave ablation, radiofrequency ablation, denosumab, cinacalcet, preoperative imaging, imaging, diagnosis, CT, PET, PET/CT, 4D/CT, SPECT/CT, F-18-fluorocholine, quality of life, fractures, and metabolic syndrome. We can say that there will be an increasing research trend on PHPT in the coming years. In addition to the Western countries such as the United States and European countries with large economies, Japan and Turkey were also identified as leading countries in the development of the PHPT literature. This study provides significant information about the intellectual structure and global productivity of PHPT to clinicians and other researchers interested on PHPT.
The effect of short-term cranial electrotherapy stimulation on sleep quality in athletes: A pilot study
Authors: Tan Chenhao , Wang Jinhao , Yin Jun , Cao Guohuan , Qiu Jun
Published: September 2023

Background:

To verify the effect of a 5-day cranial electrotherapy stimulation (CES) intervention on sleep quality in professional athletes.

Methods:

25 professional athletes with poor sleep quality participated in the study. Athletes belonging to the CES group (12 athletes) received a 5-day CES intervention, and those in the control group did not receive any intervention. Objectively and subjected assessed sleep quality was measured 1 week before and after the intervention using an Actigraphy activity recorder, Pittsburgh sleep quality index (PSQI), and Insomnia Severity Index (ISI).

Results:

Objectively measured sleep efficiency increased after CES intervention (P = .013), while the difference between the pretest and posttest of the control group was not significant. For total sleep time (TST), the main effects and interaction were not significant. However, the analysis on wake after sleep onset showed wake after sleep onset decreased after CES intervention (P = .015). No significant interaction was found in subjectively assessed sleep quality but only revealed an improvement in both groups.

Conclusion:

The CES intervention of 30 minutes per day for 5 consecutive days enhanced objective sleep quality in athletes with sleep quality problems. The intervention increased sleep efficiency by lowering awake time after falling asleep.
Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis
Authors: Ge Pu , Han Chunyan , Reyila Abudurousuli , Liu Diyue , Hong Wenying , Liu Jiaxin , Zhang Jinzi , Han Xiao , Li Xialei , Huang Mengjie , Fan Siyuan , Kaierdebieke Ayidana , Wu Xiaoyu , Huang Xiaolu , Guo Weirui , Liu Siyu , Bian Ying
Published: September 2023

Background:

Aflibercept has been approved for the treatment of metastatic colorectal cancer for more than a decade, but its antiangiogenesis adverse effect profile during treatment remains unclear. This study is conducted to systematically review the risk of antiangiogenic adverse events in patients with metastatic colorectal cancer receiving aflibercept plus chemotherapy.

Methods:

We searched databases, including PubMed, Embase and the Cochrane Library up to September 9, 2021. Relevant randomized controlled trials (RCTs) and single-arm studies were included in the review. Statistical analyses were performed using R to calculate the summary incidence rate of antiangiogenic-related adverse events, odds ratios and 95% CIs. Heterogeneity among the included studies was assessed by subgroup analysis. Publication bias analysis and sensitivity analysis were performed to confirm the reliability of the results.

Results:

A total of 2889 patients from 10 studies met the inclusion criteria. The quality of the included studies was evaluated as qualified for further quantitative synthesis. In part of single-arm studies, the occurrence rates were 44.2% (95%CI, 39.7–48.7%) for hypertension, 31.3% (95% CI, 19.3–43.3%) for proteinuria, 27.3% (95%CI, 21.2–33.4%) for epistaxis, 22.5% (95%CI, 7.8–37.3%) for hemorrhage events, 8.0% (95%CI, 2.0–14 .0%) for venous thromboembolic event in all grades and 22.6% (95%CI, 19.1–26.2%) for grade III/IV hypertension, 7.4% (95%CI, 6.2–8.5%) for grade III/IV proteinuria. In part of RCT, compared to its counterpart, aflibercept containing arm was associated with the increased incidence rate in hypertension (OR:6.30, 95%CI: 3.49–11.36), proteinuria (OR:4.12, 95%CI: 1.25–13.61), epistaxis (OR:3.71, 95%CI: 2.84–4.85), III/IV hypertension (OR:7.20, 95%CI: 5.23–9.92), III/IV proteinuria (OR:5.13, 95%CI: 3.13–8.41). The funnel plot, Begg test and Egger test were carried out on the primary endpoints, III/IV hypertension rate and III/IV proteinuria rate, the result of which detected no obvious publication bias. No significant difference was observed in subgroup analysis in the primary endpoint between the subgroups stratified by treatment line (firstline or non-firstline), chemotherapy regime (FOLFIRI or others) and study design (RCTs or single-arm trials).

Conclusion:

The available evidence suggests that using aflibercept is associated with an increased risk of antiangiogenic adverse events compared with controls. Further studies are needed to investigate this association. In the appropriate clinical scenario, the use of aflibercept in its approved indications remains justified. However, the results of this study should be interpreted with caution, as some of the evidence comes from single-arm clinical trials.
The association of ABO and Rhesus blood groups with the occurrence of type 2 diabetes mellitus: A comparative cross-sectional study
Authors: Walle Muluken , Tesfaye Addisu , Getu Fasil
Published: September 2023

Type 2 diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated levels of glucose in circulation which result from insufficient insulin or insulin resistance. The blood group of an individual is thought to be genetically predetermined and plays a vital role in increasing susceptibility to DM for particular blood groups. Therefore, this study aimed to determine the association between ABO and Rhesus blood groups with type 2 DM. A comparative cross-sectional study was conducted on 326 participants (163 type 2 DM patients and 163 age and sex-matched healthy individuals). Socio-demographic data were collected using a semi-structured questionnaire while Clinical data were extracted from the patient chart. A blood sample was collected from each study participant for ABO and Rhesus blood grouping. Chi-square test, bivariable, and multivariable logistic regression analysis were employed to indicate the association between different blood group types and type 2 DM. The current result showed that blood group O had the highest frequency among all study participants followed by blood groups B, A, and AB. Blood groups B and A were more common in the type 2 DM group compared with the control group while blood groups O and AB were more frequent in the control group. A chi-square test indicated that the ABO blood group had a significant association with type 2 DM while the Rhesus blood group was not associated with type 2 DM. Moreover, logistic regression analysis showed that B and O blood groups had a significant association with type 2 DM while A and AB blood groups had no association. The findings of this study indicated that type 2 DM has an association with the ABO blood group and has no association with the Rhesus blood group. Individuals with blood group B have a higher risk of developing T2DM (type II DM) as compared to other ABO blood groups.
Association between serum ferritin and liver stiffness in adults aged ≥20 years: A cross-sectional study based on NHANES
Authors: Han Hao , Chen Yan , Zhang Siqi , Ji Xiaojuan , Zhu Mingli , Ma Wanyu , Ge Hongfeng , Chu Hailiang
Published: September 2023

The importance of serum ferritin has been demonstrated in many liver diseases, but its relationship with liver stiffness remains unclear. The objective of this study was to investigate the association between serum ferritin levels and participants’ liver stiffness measurement (LSM) in the United States population. We conducted a screening of participants from National Health and Nutrition Examination Survey (NHANES) 2017.1 to 2020.3 to ensure that participants included in this study had complete serum ferritin and LSM information. Association between the independent variable (serum ferritin) and the dependent variable (LSM) was investigated by multiple linear regression and subgroup analysis was performed to identify sensitive individuals, and we subsequently assessed whether there was a non-linear relationship between the 2 using smoothed curve fitting and threshold effect models. The final 7143 participants were included in this study. There was a positive association between participants’ serum ferritin concentration and LSM, with an effect value of (β = 0.0007, 95% confidence interval (CI): 0.0002–0.0011) in the all-adjusted model. The smoothing curve and threshold effect models indicated a non-linear positive correlation between serum ferritin and LSM, which was more pronounced when serum ferritin concentration exceeded 440 ng/mL. Subsequent subgroup analysis showed that this positive correlation was more pronounced in males (β = 0.0007, 95% CI: 0.0001–0.0012), age >60 years (β = 0.00015, 95% CI: 0.0007–0.0023), black participants (β = 0.00018, 95% CI: 0.0009–0.0026), and participants with body mass index (BMI) <25 kg/m2 (β = 0.00012, 95% CI: 0.0005–0.0020). In U.S. adults, there was a positive correlation between serum ferritin levels and liver stiffness, which was more pronounced when serum ferritin exceeded 440 ng/mL. Our study suggested that regular serum ferritin testing would be beneficial in monitoring changes in liver stiffness. Male, age >60 years, black participants, and those with a BMI < 25 kg/m2 should be of greater consideration.
Lysosome-related genes: A new prognostic marker for lung adenocarcinoma
Authors: Hu Zeyang , Chen Hang , Li Hongxiang , Xu Shuguang , Mu Yinyu , Pan Qiaoling , Tong Jingtao , Xu Guodong
Published: September 2023

Currently, a reliable early prognostic marker has not been identified for lung adenocarcinoma (LUAD), the most common malignancy. Recent studies demonstrated that lysosomal rupture is involved in cancer migration, progression, and immune microenvironment formation. We performed a bioinformatics analysis of lysosomal rupture to investigate whether lysosome-related genes (LRGs) are key in LUAD. The analysis identified 23 LRGs. Cytoscape visualization identified 10 core genes (CCNA2, DLGAP5, BUB1B, KIF2C, PBK, CDC20, NCAPG, ASPM, KIF4A, ANLN). With the 23 LRGs, we established a new risk scoring rule to classify patients with LUAD into high- and low-risk groups and verified the accuracy of the risk score by receiver operating characteristic curves and established a nomogram to evaluate clinical patients. Immunotherapy effectiveness between the high- and low-risk groups was evaluated based on the tumor mutational burden and analyses of immune cell infiltration and drug sensitivity. Pathway enrichment analysis revealed that lysosomes were closely associated with glucose metabolism, amino acid metabolism, and the immune response in patients with LUAD. Lysosomes are a likely new therapeutic target and provide new directions and ideas for treating and managing patients with LUAD.
Construction of an aging-related risk signature in high-grade serous ovarian cancer for predicting survival outcome and immunogenicity
Authors: Liu Suxia , Liu Yuexia , Ma Jianhong , Lv Rou , Wang Fang
Published: September 2023

Studies have shown that aging significantly impacts tumorigenesis, survival outcome, and treatment efficacy in various tumors, covering high-grade serous ovarian cancer (HGSOC). Therefore, the objective for this investigation is to construct an aging-relevant risk signature for the first time, which will help evaluate the immunogenicity and survival status for patients with HGSOC. Totaling 1727 patients with HGSOC, along with their mRNA genomic data and clinical survival data, were obtained based on 5 independent cohorts. The Lasso-Cox regression model was utilized to identify the aging genes that had the most significant impact on prognosis. The risk signature was developed by integrating the determined gene expression and accordant model weights. Additionally, immunocytes in the microenvironment, signaling pathways, and immune-relevant signatures were assessed based on distinct risk subgroups. Finally, 2 cohorts that underwent treatment with immune checkpoint inhibitor (ICI) were employed to confirm the effects of identified risk signature on ICI efficacy. An aging signature was constructed from 12 relevant genes, which showed improved survival outcomes in low-risk HGSOC patients across discovery and 4 validation cohorts (all P < .05). The low-risk subgroup showed better immunocyte infiltration and higher enrichment of immune pathways and ICI predictors based on further immunology analysis. Notably, in the immunotherapeutic cohorts, low-risk aging signature was observed to link to better immunotherapeutic outcomes and increased response rates. Together, our constructed signature of aging has the potential to assess not only the prognosis outcome and immunogenicity, but also, importantly, the efficacy of ICI treatment. This signature provides valuable insights for prognosis prediction and immunotherapeutic effect evaluation, ultimately promoting individualized treatment for HGSOC patients.
Analysis of genomic alterations in primary central nervous system lymphoma
Authors: He Xin , Fan Xiaotong , Shan Yongzhi , Ji Xinrui , Su Lan , Wang Yaming
Published: September 2023

Primary central nervous system lymphoma (PCNSL) is a rare and special type of non-Hodgkin lymphoma with a significantly worse median overall prognosis than that of non-Hodgkin lymphoma outside the brain. Clarifying the genomic characteristics and alterations in PCNSL could provide clues regarding its distinctive pathophysiology and new treatment options. However, current knowledge about the genomics of PCNSL is limited. In this study, next-generation sequencing (NGS) was performed to investigate the genomic profile of PCNSL. Samples from 12 patients diagnosed with PCNSL at our institution were analyzed for gene mutations using NGS. This study showed that missense mutations were the most common mutation type. C > A/G > T accounted for most of the single-base mutations, which reflected the preference of the tumor sample mutation type and may serve as an important prognostic factor. The most significantly mutated gene was myeloid differentiation factor 88 (MYD88) (0.55), followed by CD79B, LRP1B, and PRDM1 (0.36). None of the cases showed a high tumor mutational burden. In addition to the traditional driver genes, we also identified some new possible ones such as MET, PIM1, and RSBN1L. Enrichment analysis revealed that genes mutated in PCNSL were involved in many pathways and functional protein activities, such as the extracellular matrix and adhesion molecules. The most common genetic alterations in PCNSL were identified using NGS. Mutations in multiple genes highlights the complex molecular heterogeneity of PCNSL. Enrichment analysis revealed possible pathogenesis. Further exploration of new driver genes could provide novel insights into diagnosis and precision medicine for PCNSL.
Predicting the anti-inflammatory mechanism of Radix Astragali using network pharmacology and molecular docking
Authors: Ren Jianwei , Ding Yuetian , Li Shangze , Lei Ming
Published: September 2023

According to current research, the primary active ingredients of Radix Astragali (RA), such as saponins, flavonoids, and polysaccharides, play an important role in anti-inflammatory effects. However, the exact molecular mechanism underlying the action was not elucidated to date. Our research attempted to determine the active components in RA and to investigate the interaction between the active components and targets involved in the anti-inflammation activity by network pharmacology and molecular docking. The active components and targets of RA were screened out by TCMSP. Thereafter, through the “anti-inflammation effect” and “inflammation” as the keywords, disease targets were obtained from the GeneCards database. The PPI network was constructed with Cytoscape 3.8.0 software to screen core targets. The GO function and KEGG analysis were enriched and analyzed through the Metascape platform, obtaining the 3-dimensional view of the core targets from the PDB database, and then, performing molecular docking in AutoDock Vina, a heatmap was constructed using the binding free energies in GraphPad Prism 8. The Discovery Studio software was used for docking analysis, and eventually, the docking results were visualized. We also explored the targets and signaling pathways of Astragaloside IV acting on anti-inflammatory effects via constructing compound-disease-target-pathway network. 18 active components and 45 targets of RA were screened out. The main anti-inflammatory active components of RA were quercetin, Astragaloside IV, kaempferol, 7-O-methylisomucronulatol, and formononetin, and the strongly interacting core proteins were TNF, IL6, IL1B, TLR4, CXCL8, CCL2, IL10, VEGFA, and MMP9. The signal pathways mainly involved include Lipid and atherosclerosis, IL-17 signaling pathway, Chagas disease, leishmaniasis, and TNF signaling pathway. Moreover, molecular docking showed that the 2 most active compounds, Astragaloside IV and kaempferol, could efficiently bind with the targets TNF, TLR4, and IL10. Astragaloside IV may play a part in anti-inflammatory effects through pathways such as HIF-1 signaling pathway, Inflammatory bowel disease and Hepatitis B ect. RA exhibits the characteristic of multicomponent and multitarget synergistic effects in exerting anti-inflammatory effects and the effective component of RA is Astragaloside IV, targeting TNF, TLR4, and IL10.
Identification of HOXB9 based on comprehensive bioinformatics analysis for predicting prognosis of head and neck squamous cell carcinoma
Authors: Li Juanjuan , Ran Hong , Zeng Xiaoxia , Yang Dunhui , Zeng Xianhai , Zhang Peng
Published: September 2023

To evaluate the correlation between HOXB9 expression, and the prognosis and immune infiltration in head and neck squamous cell carcinoma (HNSCC). Pan-cancer HOXB9 expression was analyzed through TIMER2.0. The HOXB9 expression data of HNSCC and normal tissues were compared using the gene expression profiling interactive analysis (GEPIA) and the cancer genome atlas (TCGA) databases. The University of Alabama at Birmingham (UALCAN) database was used to analyze the relative expression of HOXB9 in HNSCC subgroups based on clinicopathological features, including cancer stage, tumor grade and lymph node stage. Survival analysis was performed using GEPIA, TCGA-Portal, Kaplan–Meier Plotter, and UALCAN databases. The genes co-expressed with HOXB9 were identified using TCGA data, and functionally annotated by GO and KEGG analyses. Protein-protein interaction network was constructed using the STRING database and Cytoscape 3.7.1. Single-sample gene set enrichment analysis was performed to assess the correlation between HOXB9 and immune infiltration based on TCGA data. TIMER 2.0 database was used to explore the correlation between HOXB9 expression and immune infiltration multiple cancers. HOXB9 mRNA is elevated in multiple cancers, and was upregulated in HNSCC tissues compared to non-paired (P < .05 in GEPIA; P < .0001 in TCGA) as well as paired (P < .0001 in TCGA) normal tissues. In addition, HOXB9 expression was positively correlated with tumor malignancy in the GEPIA and UALCAN databases (P < .05), and negatively with patient prognosis in both databases (P < .05). High HOXB9 expression was associated with increased infiltration of aDCs, NK CD56bright cells, NK cells, and Th2 cells (P < .05), while low HOXB9 expression was associated with an increase in the proportion of DCs, iDCs, mast cells, neutrophils, and Th17 cells (P < .05). HOXB9 likely functions as an oncogene in HNSCC by disrupting the immune landscape, and is a promising prognostic biomarker and therapeutic target.
Triple therapy in metastatic hormone-sensitive prostate cancer
Authors: Tsaur Igor , Mirvald Cristian , Surcel Cristian
Published: September 2023

Purpose of review

Over the last years, there have been striking changes in the management of metastatic hormone-sensitive prostate cancer (mHSPC) based on survival advantage of combining either a new hormonal agent (NHA) or docetaxel (D) with androgen deprivation therapy (ADT). Some of these studies primarily assessing doublet treatment included men who underwent concomitant or sequential treatment with D. Most recently, prospective randomized evidence emerged on this triplet strategy too. We aimed to outline the current data and ongoing trials evaluating the usage of the triplet therapy in male individuals with mHSPC.

Recent findings

Phase III trials PEACE-1 and ARASENS showed that the upfront triplet treatment with ADT+D and either abiraterone acetate or darolutamide outperformed ADT+D in terms of survival, while severe toxicity was mainly driven by D. Importantly, prospective evidence comparing triplet vs. ADT+NHA is still lacking.

Men with de novo high-volume disease benefit most from the triplet, while in cases with metachronous and/or low-volume disease, survival advantage is still disputable. As efficacy of ADT+NHA does not appear to be substantially amplified by combination with D, those men with a more favorable underlying tumor biology might mostly benefit from this doublet, also taking quality-adjusted survival into account.
ChatGPT and artificial hallucinations in stem cell research: assessing the accuracy of generated references – a preliminary study
Authors: Sharun Khan , Banu S. Amitha , Pawde Abhijit M. , Kumar Rohit , Akash Shopnil , Dhama Kuldeep , Pal Amar
Published: September 2023

Stem cell research has the transformative potential to revolutionize medicine. Language models like ChatGPT, which use artificial intelligence (AI) and natural language processing, generate human-like text that can aid researchers. However, it is vital to ensure the accuracy and reliability of AI-generated references. This study assesses Chat Generative Pre-Trained Transformer (ChatGPT)’s utility in stem cell research and evaluates the accuracy of its references. Of the 86 references analyzed, 15.12% were fabricated and 9.30% were erroneous. These errors were due to limitations such as no real-time internet access and reliance on preexisting data. Artificial hallucinations were also observed, where the text seems plausible but deviates from fact. Monitoring, diverse training, and expanding knowledge cut-off can help to reduce fabricated references and hallucinations. Researchers must verify references and consider the limitations of AI models. Further research is needed to enhance the accuracy of such language models. Despite these challenges, ChatGPT has the potential to be a valuable tool for stem cell research. It can help researchers to stay up-to-date on the latest developments in the field and to find relevant information.
Cocreation With Prelicensure Nursing Students of a Simulated Practice Placement
Authors: Salje Joelle
Published: September 2023

Background:

Cocreation is a collaborative process that uses problem-based learning to construct new initiatives. It has many known benefits associated with innovation in the development of programs, such as by creating simulations based on firsthand experiences.

Methods:

Thirty second-year prelicensure nursing students cocreated simulations and associated lesson plans for a simulated practice placement. They followed a 4-step process described in the article.

Results:

Cocreation combines lecturers' and students' unique skills and knowledge, creating programs based on the unique firsthand experiences of stakeholders. As the students take control of their own workloads, facilitators need to be adaptable in the support they provide, depending on the needs of the students.

Conclusion:

The staged process provided a structure for the students to produce their simulations and lesson plans. The cocreation of the simulated practice placement provided an innovative educational model that supported student development and produced lessons and simulations based on stakeholder need.
Vaccine Hesitancy
Authors: Hekel Barbara E. , Dugger Jennifer , Pullis Bridgette R. , Cron Stanley , Edwards Allison P.
Published: September 2023

Background:

Many Americans are undecided about or have barriers to receiving vaccines. Complacency, confidence, convenience, misinformation, and disinformation impact vaccine hesitancy (VH).

Problem:

During the COVID-19 pandemic, rates for flu and routine childhood vaccinations declined globally. As vaccination rates decline, the risk of disease outbreaks increases. Nursing students need to be prepared to address VH in the clinical setting.

Approach:

Four simulation experiences were developed to build confidence and competency in the provision of vaccinations and addressing VH. Nursing students practiced communication skills critical to motivational interviewing, health education, health promotion, and goal setting.

Outcome:

There were statistically significant increases in student confidence and perceived competence in vaccine administration and addressing VH through motivational interviewing.

Conclusions:

High-fidelity simulation combined with a virtual simulation was effective in developing confidence among nursing students. Students demonstrated skill in addressing VH and motivational interviewing.
Technical Factors That May Influence mHealth Adherence in Children With Chronic Pulmonary Diseases: Scoping Review
Authors: Sapouna Vaia , Dimitriadis Zacharias , Douros Konstantinos , Kapreli Eleni , Kortianou Eleni A.
Published: September 2023

Purpose:

To synthesize the technical factors influencing adherence to nonpharmacological treatment (NPhT) in children with chronic pulmonary diseases (CPDs), using mobile health (mHealth) technology.

Methods:

Five electronic databases were searched from inception to October 12, 2022, with terms related to pediatrics, CPDs, adherence, NPhT, and mHealth. The methodological quality was assessed using the Critical Appraisal Skills Programme and the Mixed Methods Appraisal Tool checklist.

Results:

Eleven articles were included. Six major technical themes were supported by the evidence that may influence adherence to NPhT: design and context, technical support/business model, connectivity, free availability, privacy and security, and cultural readiness.

Conclusions:

The design of mHealth applications (apps) should be done according to the needs of pediatric patients. This may mitigate any barriers and potentially foster adherence to the use of the apps.

What This Adds to the Evidence:

Six major technical themes may influence adherence to NPhT in children with chronic respiratory diseases.

Video Abstract: Supplemental digital content available at http://links.lww.com/PPT/A487.
Effect of Active Motor Learning Interventions on Gross Motor Function and Mobility in Children Aged 2 to 6 Years With Bilateral Cerebral Palsy: A Systematic Review and Meta-analysis
Authors: McLeod Kate L. , Thorley Megan , Reedman Sarah E. , Chatfield Mark D. , Sakzewski Leanne
Published: September 2023

Purpose:

The purpose of this systematic review is to identify evidence-based interventions to promote active motor learning in children aged 2 to 6 years with bilateral cerebral palsy.

Summary of Key Points:

Seven randomized clinical trials of active motor learning interventions targeting gross motor function and mobility were included. Two studies compared context-focused therapy to child-focused therapy. Five studies compared active motor therapy to usual care. Context-focused therapy, child-focused therapy, and active motor therapy were comparable to usual care to improve functional mobility and gross motor function.

Conclusions and Recommendations for Clinical Practice:

There are limited active intervention studies targeting gross motor function for young children with bilateral cerebral palsy. The authors recommend consideration of the clinical good practice guidelines, dosage parameters, and improved reporting methods when implementing active motor learning interventions targeting gross motor function and mobility for children with cerebral palsy.
Psychosocial Outcomes in Nondirected Uterus Donors 1 Y After Donation
Authors: Warren Ann Marie , da Graca Briget , Wall Anji , Powers Mark B. , Saracino Giovanna , Testa Giuliano , Johannesson Liza
Published: September 2023

Background.

As uterus transplantation transitions to a clinical procedure for women with absolute uterine-factor infertility, transplant centers performing uterus transplantation need information about the experience of living donors. This study examined the psychosocial impact on 17 nondirected uterus donors in the Dallas UtErus Transplant Study 1 y following donation.

Methods.

A prospective longitudinal study was conducted to measure psychosocial outcomes of depression, anxiety, posttraumatic stress, quality of life, and resilience [measured using the Hospital Anxiety and Depression Scale or Patient Health Questionnaire 9-Item, Generalized Anxiety Disorder 7-Item, Posttraumatic Stress Disorder Checklist for the DSM-5, health-related quality of life Short Form-36, and Connor-Davidson Resilience Scale 10-Item, respectively) assessed at baseline, at 6-mo and 1-y follow-up. Differences among baseline, 6-mo, and 1-y postdonation were analyzed.

Results.

The median age was 38.0 y, 16 were married, 15 were of non-Hispanic/Latino ethnicity. Most donors did not report psychosocial distress; however, 1 donor reported decline on the role limitations because of Emotional Problems Scale and also showed an increase in depression symptoms at the 6 mo, but at 1 y was below the clinical cutoff for depression. A second donor showed modest decline in emotional well-being. Improvements were seen in other donors on the Physical Functioning Scale and posttraumatic stress symptoms.

Conclusions.

Although most nondirected donors appeared to remain stable, both positive and negative changes were observed over the first year. Larger studies are needed to determine psychosocial risks and benefit and what additional resources might be needed to ensure optimal psychosocial outcomes.
Antiviral activity of salt-coated materials against SARS-CoV-2.
Authors: Coleman Christopher Michael , Wang Belinda , Wang Yixin , Tapia-Brito Emmanuel , Chen Ziwei , Riffat James , Riffat Saffa , Tarlinton Rachael , Ghaemmaghami Amir
Published: September 2023

The SARS-CoV-2 pandemic demonstrated the importance of human coronaviruses and the need to develop materials to prevent the spread of emergent viruses. Here we describe that simple salt coating on a range of surfaces can degrade SARS-CoV-2.
Staph wars: the antibiotic pipeline strikes back
Authors: Douglas Edward J.A. , Laabei Maisem
Published: September 2023

Antibiotic chemotherapy is widely regarded as one of the most significant medical advancements in history. However, the continued misuse of antibiotics has contributed to the rapid rise of antimicrobial resistance (AMR) globally.

Staphylococcus aureus

, a major human pathogen, has become synonymous with multidrug resistance and is a leading antimicrobial-resistant pathogen causing significant morbidity and mortality worldwide. This review focuses on (1) the targets of current anti-staphylococcal antibiotics and the specific mechanisms that confirm resistance; (2) an in-depth analysis of recently licensed antibiotics approved for the treatment of

S. aureus

infections; and (3) an examination of the pre-clinical pipeline of anti-staphylococcal compounds. In addition, we examine the molecular mechanism of action of novel antimicrobials and derivatives of existing classes of antibiotics, collate data on the emergence of resistance to new compounds and provide an overview of key data from clinical trials evaluating anti-staphylococcal compounds. We present several successful cases in the development of alternative forms of existing antibiotics that have activity against multidrug-resistant

S. aureus

. Pre-clinical antimicrobials show promise, but more focus and funding are required to develop novel classes of compounds that can curtail the spread of and sustainably control antimicrobial-resistant

S. aureus

infections.
Identifying X-Chromosome Variants Associated with Age-Related Macular Degeneration
Authors: Grunin Michelle , Igo Robert P. , Song Yeunjoo E , Blanton Susan H , Pericak-Vance Margaret A , Haines Jonathan L. ,   International Age-related Macular Degeneration Genomics Consortium
Published: September 2023

Purpose

In genome-wide association studies (GWAS), X chromosome (ChrX) variants are often not investigated. Sex-specific effects and ChrX-specific quality control (QC) are needed to examine these effects. Previous analyses identified 52 autosomal variants associated with age-related macular degeneration (AMD) via the International AMD Genomics Consortium (IAMDGC), but did not analyze ChrX. Therefore, our goal was to investigate ChrX variants for association with AMD.

Methods

We genotyped 29,629 non-Hispanic White (NHW) individuals (M/F:10,404/18,865; AMD12,087/14723) via a custom chip and imputed after ChrX-specific QC (XWAS 3.0) using the Michigan Imputation Server. Imputation generated 1,221,623 variants on ChrX. Age, informative PCs, and subphenotyeps were covariates for logistic association analyses with Fishers correction. Gene/pathway analyses were performed with VEGAS, GSEASNP, ICSNPathway, DAVID, and mirPath.

Results

Logistic association on NHW individuals with sex correction, identified variants in/near the genesSLITRK4, ARHGAP6, FGF13andDMDassociated with AMD (P<1x10-6,Fishers combined-corrected). Via association testing of subphenotypes of choroidal neovascularization and geographic atrophy (GA), variants inDMDassociated with GA (P<1x10-6, Fishers combined-corrected). Via gene-based analysis with VEGAS, several genes were associated with AMD (P<0.05, both truncated tail strength/truncated product P) includingSLITRK4andBHLHB9. Pathway analysis using GSEASNP and DAVID showed genes associated with nervous system development (FDR: P:0.02), and blood coagulation (FDR: P:0.03). Variants in the region of a microRNA (miR) were associated with AMD (P<0.05, truncated tail strength/truncated product P). Via DIANA mirPath analysis, downstream targets of miRs show association with brain disorders and fatty acid elongation (P<0.05). A long-non coding RNA on ChrX near theDMDlocus was also associated with AMD (P=4x10-7). Epistatic analysis (t-statistic) for a quantitative trait of AMD vs control including covariates found a suggestive association in theXGgene (P=2x10^-5).

Conclusions

Analysis of ChrX variants demonstrates association with AMD and these variants may be linked to novel pathways. Further analysis is needed to confirm results and to understand their biological significance and relationship with AMD development in worldwide populations.