Validity and reliability of the Chinese version of human-robot interaction self-efficacy scale in Chinese adults.

BACKGROUND: With the fast-paced advancements of robot technology, human-robot interaction (HRI) has become increasingly popular and complex, and self-efficacy in HRI has received extensive attention. Despite its popularity, this topic remains understudied in China. OBJECTIVE: In order to provide a psychometrically sound instrument in China, this study aimed to translate and validate the Self-Efficacy in Human-Robot Interaction Scale (SE-HRI) in two Chinese adult samples (N1 = 300, N2 = 500). METHODS: The data was analyzed by SPSS 26.0 and Amos 24.0. Item analysis and exploratory factor analysis were conducted using Sample 1 data. Confirmatory factor analysis, criterion-related validity analysis, and reliability analysis were then performed using Sample 2 data. RESULTS: The results revealed that the Chinese SE-HRI scale consisted of 13 items in a two-factor model, suggesting a good model fit. Moreover, general self-efficacy and willingness to accept the use of artificial intelligence (AI) were both positively correlated with self-efficacy in HRI, while negative attitudes toward robots showed an inverse correlation, proving the Chinese SE-HRI scale exhibited excellent criterion-related validity. CONCLUSION: The Chinese SE-HRI scale is a reliable assessment tool for evaluating self-efficacy in HRI in China. The study discussed implications and limitations, and suggested future directions.

Plasma ctDNA enhances the tissue-based detection of oncodriver mutations in colorectal cancer.

PURPOSE: The advent of circulating tumor DNA (ctDNA) technology has provided a convenient and noninvasive means to continuously monitor cancer genomic data, facilitating personalized cancer treatment. This study aimed to evaluate the supplementary benefits of plasma ctDNA alongside traditional tissue-based next-generation sequencing (NGS) in identifying targetable mutations and tumor mutational burden (TMB) in colorectal cancers (CRC). METHODS: Our study involved 76 CRC patients, collecting both tissue and plasma samples for NGS. We assessed the concordance of gene mutational status between ctDNA and tissue, focusing on actionable genes such as KRAS, NRAS, PIK3CA, BRAF, and ERBB2. Logistic regression analysis was used to explore variables associated with discordance and positive mutation rates. RESULTS: In total, 26 cancer-related genes were identified. The most common variants in tumor tissues and plasma samples were in APC (57.9% vs 19.7%), TP53 (55.3% vs 22.4%) and KRAS (47.4% vs 43.4%). Tissue and ctDNA showed an overall concordance of 73.53% in detecting actionable gene mutations. Notably, plasma ctDNA improved detection for certain genes and gene pools. Variables significantly associated with discordance included gender and peritoneal metastases. TMB analysis revealed a higher detection rate in tissues compared to plasma, but combining both increased detection. CONCLUSIONS: Our study highlights the importance of analyzing both tissue and plasma for detecting actionable mutations in CRC, with plasma ctDNA offering added value. Discordance is associated with gender and peritoneal metastases, and TMB analysis can benefit from a combination of tissue and plasma data. This approach provides valuable insights for personalized CRC treatment.

Silencing of matrix metalloprotease-12 delays the progression of castration-resistant prostate cancer by regulating autophagy and lipolysis.

The complex pathogenesis of castration-resistant prostate cancer (CRPC) makes it challenging to identify effective treatment methods. Matrix metalloproteinase (MMP)-12 can degrade elastin as well as various extracellular matrix (ECM) components, which is associated with cancer progression. However, the relationship between MMP-12 and CRPC progression is poorly understood. In this study, we observed the effect of MMP-12 on the progression of CRPC and further explored its potential mechanism of action. High levels of MMP-12 were observed in patients with CRPC. We therefore developed cell co-culture and mouse models to study the function of MMP-12. Silencing MMP-12 in CRPC cells disrupted lipid utilization and autophagy marker expression via the CD36/CPT1 and P62/LC3 pathways, respectively, leading to reduced CRPC cell migration and invasion. Moreover, animal experiments confirmed that MMP-12-knockdown CRPC xenograft tumors exhibited reduced tumor growth, and the mechanisms involved the promotion of cancer cell autophagy and the inhibition of lipid catabolism. According to our results, MMP-12 played important roles in the progression of CRPC by disrupting adipocyte maturation and regulating cancer migration and invasion via the modulation of autophagy and lipid catabolism pathways.

Silencing of matrix metalloprotease-12 delays the progression of castration-resistant prostate cancer by regulating autophagy and lipolysis

Abstract The complex pathogenesis of castration-resistant prostate cancer (CRPC) makes it challenging to identify effective treatment methods. Matrix metalloproteinase (MMP)-12 can degrade elastin as well as various extracellular matrix (ECM) components, which is associated with cancer progression. However, the relationship between MMP-12 and CRPC progression is poorly understood. In this study, we observed the effect of MMP-12 on the progression of CRPC and further explored its potential mechanism of action. High levels of MMP-12 were observed in patients with CRPC. We therefore developed cell co-culture and mouse models to study the function of MMP-12. Silencing MMP-12 in CRPC cells disrupted lipid utilization and autophagy marker expression via the CD36/CPT1 and P62/LC3 pathways, respectively, leading to reduced CRPC cell migration and invasion. Moreover, animal experiments confirmed that MMP-12-knockdown CRPC xenograft tumors exhibited reduced tumor growth, and the mechanisms involved the promotion of cancer cell autophagy and the inhibition of lipid catabolism. According to our results, MMP-12 played important roles in the progression of CRPC by disrupting adipocyte maturation and regulating cancer migration and invasion via the modulation of autophagy and lipid catabolism pathways.

Unraveling the genetic associations between PD-1/PD-L1 and 13 circulating biomarkers linked to physiological and pathological processes.

BACKGROUND: Evidence of the genetic interconnectedness between PD-1/PD-L1 and circulating biomarkers related to physiological and pathological processes is largely unclear. Understanding these genetic links is crucial for gaining insights into the underlying mechanisms and potential implications in cancer immunotherapy. METHODS: To shed light on potential roles of 90 circulating biomarkers in PD-1/PD-L1, we conducted a comprehensive Mendelian randomization (MR) analysis, leveraging genetic data from large-scale genome-wide association studies. RESULTS: Our results revealed negative associations between EN-RAGE and TRAIL-R2 with PD-1 levels. Additionally, we observed that PD-1 levels were positively associated with TRAIL, VEGF, and ANPEP, indicating their potential role in PD-1 upregulation. Furthermore, our analysis revealed causal associations between several circulating proteins and PD-L1 levels. Thrombomodulin, PSGL-1, TNFSF14, renin, follistatin, ß-NGF, KLK6, and MMP-7 demonstrated significant effects on PD-L1 regulation, suggesting their potential inhibitory role in immune checkpoint regulation. Eventually, we confirmed the potential roles of key genes involved in above circulating proteins in influencing the response to immunotherapy. CONCLUSIONS: Our findings provide valuable evidence of the genetic interconnectedness between PD-1/PD-L1 and circulating proteins related to physiological and pathological processes, shedding light on their potential roles in disease progression and therapeutic interventions.

Efeitos do modelo de enfermagem de Newman na qualidade de vida e recuperação muscular do assoalho pélvico em pacientes com disfunção do assoalho pélvico pós-parto / Efectos del modelo de enfermería de Newman en la calidad de vida y recuperación muscular del suelo pélvico en pacientes con disfunción del suelo pélvico posparto / Effects of the Newman nursing model on quality of life and pelvic floor muscle recovery in patients with postpartum pelvic floor dysfunction

Resumo Objetivo Avaliar os efeitos do modelo de enfermagem de Newman na qualidade de vida e recuperação muscular do assoalho pélvico em pacientes com disfunção do assoalho pélvico pós-parto. Métodos Oitenta e oito pacientes com disfunção do assoalho pélvico pós-parto tratadas de janeiro a abril de 2023 foram divididas em grupo Observação e Controle (n=44) por meio de tabela de números aleatórios. O grupo Controle recebeu enfermagem de rotina e o grupo Observação recebeu cuidados de enfermagem de Newman. A qualidade de vida foi avaliada pelo Short Form-36 Health Status Questionnaire. A função do assoalho pélvico foi avaliada por meio do Pelvic Floor Impact Questionnaire-7 (PFIQ7) e da Pelvic Organ Prolapse Quantification (POPQ). Resultados Após a intervenção, as pontuações de aspectos físico, emocional, capacidade funcional, social e motor do grupo Observação foram superiores às do grupo Controle (P<0,05). As pontuações da Escala de Autoavaliação de Ansiedade e da Escala de Autoavaliação de Depressão do grupo Observação foram inferiores às do grupo Controle. O nível de conhecimento sobre a doença foi maior no grupo Observação do que no grupo Controle (P<0,05). O grupo Observação apresentou maior força das fibras musculares tipo I e II, e menores graus de fadiga das fibras musculares tipo I e II do que o grupo Controle (P<0,05). As pontuações PEIQ7 e POPQ do grupo Observação foram inferiores às do grupo Controle (P<0,05). Conclusão O modelo de enfermagem de Newman ajuda a melhorar a função do assoalho pélvico, a qualidade de vida e o conhecimento sobre a doença, além de aliviar a ansiedade, a depressão e outras emoções adversas.

Resumen Objetivo Evaluar los efectos del modelo de enfermería de Newman en la calidad de vida y recuperación muscular del suelo pélvico en pacientes con disfunción del suelo pélvico posparto. Métodos Un grupo de 88 pacientes con disfunción del suelo pélvico posparto, tratadas de enero a abril de 2023, fue dividido en dos grupos, uno de observación y otro de control (n=44) mediante una tabla de número aleatorios. El grupo de control recibió cuidados de enfermería de rutina y el grupo de observación recibió cuidados de enfermería de Newman. Se utilizó el Short Form-36 Health Status Questionnaire para evaluar la calidad de vida. La función del suelo pélvico se evaluó mediante el Pelvic Floor Impact Questionnaire-7 (PFIQ7) y la Pelvic Organ Prolapse Quantification (POPQ). Resultados Después de la intervención, el puntaje de los aspectos físico, emocional, social, motor y de la capacidad funcional del grupo de observación fue más alto que el del grupo de control (P<0,05). El puntaje de la Escala de Autoevaluación de Ansiedad y de la Escala de Autoevaluación de Depresión del grupo de observación fue más bajo que el del grupo de control. El nivel de conocimiento sobre la enfermedad fue mayor en el grupo de observación que en el grupo de control (P<0,05). El grupo de observación presentó mayor fuerza de las fibras musculares tipo I y II y un nivel menor de fatiga de las fibras musculares tipo I y II que el grupo de control (P<0,05). El puntaje de PEIQ7 y POPQ del grupo de observación fue más bajo que el del grupo de control (P<0,05). Conclusión El modelo de enfermería de Newman ayuda a mejorar la función del suelo pélvico, la calidad de vida y el conocimiento sobre la enfermedad, además de calmar la ansiedad, la depresión y otras emociones adversas.

Abstract Objective We aimed to evaluate the effects of the Newman nursing model on the quality of life and pelvic floor muscle recovery in patients with postpartum pelvic floor dysfunction. Methods Eighty-eight patients with postpartum pelvic floor dysfunction treated from January to April 2023 were divided into observation and control groups (n=44) using a random number table. The control group was given routine nursing, based on which the observation group was given Newman nursing. The quality of life was assessed by the Short Form-36 Health Status Questionnaire. The pelvic floor function was evaluated using the Pelvic Floor Impact Questionnaire-7 (PEIQ7) and Pelvic Organ Prolapse Quantification (POPQ). Results After intervention, the scores of role physical, language communication, physical functioning, social functioning and motor functioning of the observation group were higher than those of the control group (P<0.05). The Self-rating Anxiety Scale and Self-rating Depression Scale scores of the observation group were lower than those of the control group. The awareness rate of disease knowledge of the observation group was higher than that of the control group (P<0.05). The observation group had higher class I and class II muscle fiber potentials, whereas lower class I and class II muscle fiber fatigue degrees than those of the control group (P<0.05). The PEIQ7 and POPQ scores of the observation group were lower than those of the control group (P<0.05). Conclusion Newman nursing helps improve the pelvic floor function, quality of life and awareness of the disease knowledge, and relieve anxiety, depression and other adverse emotions.

The novel roles of YULINK in the migration, proliferation and glycolysis of pulmonary arterial smooth muscle cells: implications for pulmonary arterial hypertension.

BACKGROUND: Abnormal remodeling of the pulmonary vasculature, characterized by the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) along with dysregulated glycolysis, is a pathognomonic feature of pulmonary arterial hypertension (PAH). YULINK (MIOS, Entrez Gene: 54468), a newly identified gene, has been recently shown to possess pleiotropic physiologic functions. This study aims to determine novel roles of YULINK in the regulation of PAH-related pathogenesis, including PASMC migration, proliferation and glycolysis. RESULTS: Our results utilized two PAH-related cell models: PASMCs treated with platelet-derived growth factor (PDGF) and PASMCs harvested from monocrotaline (MCT)-induced PAH rats (PAH-PASMCs). YULINK modulation, either by knockdown or overexpression, was found to influence PASMC migration and proliferation in both models. Additionally, YULINK was implicated in glycolytic processes, impacting glucose uptake, glucose transporter 1 (GLUT1) expression, hexokinase II (HK-2) expression, and pyruvate production in PASMCs. Notably, YULINK and GLUT1 were observed to colocalize on PASMC membranes under PAH-related pathogenic conditions. Indeed, increased YULINK expression was also detected in the pulmonary artery of human PAH specimen. Furthermore, YULINK inhibition led to the suppression of platelet-derived growth factor receptor (PDGFR) and the phosphorylation of focal adhesion kinase (FAK), phosphoinositide 3-kinase (PI3K), and protein kinase B (AKT) in both cell models. These findings suggest that the effects of YULINK are potentially mediated through the PI3K-AKT signaling pathway. CONCLUSIONS: Our findings indicate that YULINK appears to play a crucial role in the migration, proliferation, and glycolysis in PASMCs and therefore positioning it as a novel promising therapeutic target for PAH.

A-80426 suppresses CFA-induced inflammatory pain by suppressing TRPV1 activity via NFκB and PI3K pathways in mice.

OBJECTIVES: Pain is associated with many circumstances, including inflammatory reactions, which arise from modification of the features of signaling pathways. α2-adrenergic receptor antagonists are widely utilized in narcosis. Here, the authors focused on the narcotic effect of A-80426 (A8) on Complete Freund's Adjuvant (CFA) injections-triggered chronic inflammation pain in WT and TRPV1-/- mice and explored whether its antinociceptive impact was modulated via Transient Receptor Potential Vanilloid 1 (TRPV1). METHOD: CFA with or without A8 was co-administered to the mice, which were categorized randomly into four groups: CFA, A8, control, and vehicle. Pain behaviors underwent evaluation through mechanical withdrawal threshold, abdominal withdrawal reflex, and thermal withdrawal latency of WT animals. RESULTS: Quantitative polymerase chain reaction revealed that inflammation-promoting cytokines (IL-1ß, IL-6, and TNF-α) were upregulated in Dorsal Root Ganglion (DRG) and Spinal Cord Dorsal Horn (SCDH) tissues of WT animals. A8 administration reduced the pain behaviors and production of pro-inflammatory cytokines; however, this effect was significantly reduced in TRPV1-/- mice. Further analysis showed that CFA treatment reduced the TRPV1 expression in WT mice and A8 administration increased its expression and activity. The co-administration of SB-705498, a TRPV1 blocker, did not influence the pain behaviors and inflammation cytokines in CFA WT mice; however, SB-705498 the effect of A8 in WT mice. In addition, the TRPV1 block decreased the NFκB and PI3K activation in the Dorsal Root Ganglia (DRG) and Spinal Cord Dorsal Horn (SCDH) tissues of WT mice. CONCLUSIONS: Together, A8 exerted a narcotic impact on CFA-supplemented mice via the TRPV1-modulated NFκB and PI3K pathway.

The role and clinical significance of microRNA-29a-3p in the development of hypopharyngeal carcinoma

Abstract Objective MicroRNA-29a-3p has been reported in a variety of cancers, but its role in hypopharyngeal cancer remains unclear. This study was to determine the role of microRNA-29a-3p in the occurrence and development of hypopharyngeal cancer. Methods 40 patients with hypopharyngeal cancer who underwent surgery in the Affiliated Hospital of Jining Medical University from April 2013 to November 2017 were selected for this study. The cancer tissue samples of the patients were collected, and the patients were followed up for three years. The expression of microRNA-29a-3p in tissue samples was detected by in situ hybridization with fluorescent probe, and the relationships among microRNA-29a-3p and clinicopathological factors, postoperative recurrent-metastasis, survival time were studied. Immunohistochemical was used to detect the expression of Ki67 and E-cadherin in tissue samples. Results Combined with HE staining results showed that microRNA-29a-3p expression was relatively high in non-cancer tissue cells (red blood cells and fibroblasts in tumor interstitial vessels), but was relatively low in cancer tissue and cells. According to the follow-up data of 40 patients with hypopharyngeal cancer, tumor size, T-stage, tumor differentiation, postoperative recurrent-metastasis of hypopharyngeal cancer patients were significantly negatively correlated with microRNA-29a-3p (p< 0.05). Immunohistochemica results further confirmed that microRNA-29a-3p was negatively correlated with the expression of Ki67 and E-cadherin. The survival time of patients positively related with microRNA-29a-3p expression (p< 0.05). Moreover, ROC curve analysis showed that the area under the curve of the combined detection of miRNA-29a-3p+Ki67+E-cadherin was larger than that of the single detection of the three indexes. Conclusions The expression of microRNA-29a-3p is closely related to the occurrence, development and prognosis of hypopharyngeal cancer, and it affects the proliferation and invasion. This indicates that microRNA-29a-3p serves as a therapeutic target for the occurrence and development of hypopharyngeal cancer. The evidence of study designs of this study is IV using "Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence".

Effect of tinnitus on sound localization ability in patients with normal hearing

Abstract Objectives To determine whether tinnitus negatively impacts the accuracy of sound source localization in participants with normal hearing. Methods Seventy-five participants with tinnitus and 74 without tinnitus were enrolled in this study. The accuracy of sound source discrimination on the horizontal plane was compared between the two participant groups. The test equipment consisted of 37 loudspeakers arranged in a 180° arc facing forward with 5° intervals between them. The stimuli were pure tones of 0.25, 0.5, 1, 2, 4, and 8 kHz at 50 dB SPL. The stimuli were divided into three groups: low frequency (LF: 0.25, 0.5, and 1 kHz), 2 kHz, and high frequency (HF: 4 and 8 kHz) stimuli. Results The Root Mean Square Error (RMSE) score of all the stimuli in the tinnitus group was significantly higher than that in the control group (13.45 ± 3.34 vs. 11.44 ± 2.56, p = 4.115, t < 0.001). The RMSE scores at LF, 2 kHz, and HF were significantly higher in the tinnitus group than those in the control group (LF: 11.66 ± 3.62 vs. 10.04 ± 3.13, t = 2.918, p = 0.004; 2 kHz: 16.63 ± 5.45 vs. 14.43 ± 4.52, t = 2.690, p = 0.008; HF: 13.42 ± 4.74 vs. 11.14 ± 3.68, t = 3.292, p = 0.001). Thus, the accuracy of sound source discrimination in participants with tinnitus was significantly worse than that in those without tinnitus, despite the stimuli frequency. There was no difference in the ability to localize the sound of the matched frequency and other frequencies (12.86 ± 6.29 vs. 13.87 ± 3.14, t = 1.204, p = 0.236). Additionally, there was no correlation observed between the loudness of tinnitus and RMSE scores (r = 0.096, p = 0.434), and the Tinnitus Handicap Inventory (THI) and RMSE scores (r = −0.056, p = 0.648). Conclusions Our present data suggest that tinnitus negatively impacted sound source localization accuracy, even when participants had normal hearing. The matched pitch and loudness and the impact of tinnitus on patients' daily lives were not related to the sound source localization ability. Level of evidence 4.

The role and clinical significance of microRNA-29a-3p in the development of hypopharyngeal carcinoma.

OBJECTIVE: MicroRNA-29a-3p has been reported in a variety of cancers, but its role in hypopharyngeal cancer remains unclear. This study was to determine the role of microRNA-29a-3p in the occurrence and development of hypopharyngeal cancer. METHODS: 40 patients with hypopharyngeal cancer who underwent surgery in the Affiliated Hospital of Jining Medical University from April 2013 to November 2017 were selected for this study. The cancer tissue samples of the patients were collected, and the patients were followed up for three years. The expression of microRNA-29a-3p in tissue samples was detected by in situ hybridization with fluorescent probe, and the relationships among microRNA-29a-3p and clinicopathological factors, postoperative recurrent-metastasis, survival time were studied. Immunohistochemical was used to detect the expression of Ki67 and E-cadherin in tissue samples. RESULTS: Combined with HE staining results showed that microRNA-29a-3p expression was relatively high in non-cancer tissue cells (red blood cells and fibroblasts in tumor interstitial vessels), but was relatively low in cancer tissue and cells. According to the follow-up data of 40 patients with hypopharyngeal cancer, tumor size, T-stage, tumor differentiation, postoperative recurrent-metastasis of hypopharyngeal cancer patients were significantly negatively correlated with microRNA-29a-3p (p < 0.05). Immunohistochemica results further confirmed that microRNA-29a-3p was negatively correlated with the expression of Ki67 and E-cadherin. The survival time of patients positively related with microRNA-29a-3p expression (p < 0.05). Moreover, ROC curve analysis showed that the area under the curve of the combined detection of miRNA-29a-3p+Ki67+E-cadherin was larger than that of the single detection of the three indexes. CONCLUSIONS: The expression of microRNA-29a-3p is closely related to the occurrence, development and prognosis of hypopharyngeal cancer, and it affects the proliferation and invasion. This indicates that microRNA-29a-3p serves as a therapeutic target for the occurrence and development of hypopharyngeal cancer. The evidence of study designs of this study is IV using "Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence".

Nutrition management by a multidisciplinary team for prevention of nutritional deficits and morbidity following esophagectomy.

This study evaluated the effects of perioperative nutrition management by a multidisciplinary team on nutrition and postoperative complications of patients with esophageal cancer. A total of 239 patients with esophageal cancer who underwent esophagectomy and gastric conduit reconstruction for esophageal or esophagogastric junction cancer between February 2019 and February 2020 were included in the study. They were divided into the experimental group (120 patients) and the control group (119 patients) using the random number table method. Control group patients received routine diet management and experimental group patients received perioperative nutrition management by a multidisciplinary team. The differences of nutriture and postoperative complications between the two groups were compared. At 3 and 7 days after surgery, the experimental group patients had higher total protein and albumin levels (P<0.05), shorter postoperative anal exhaust time (P<0.05), lower incidence of postoperative gastrointestinal adverse reactions, pneumonia, anastomotic fistula, hypoproteinemia (P<0.05), and lower hospitalization costs (P<0.05) than the control group. Nutrition management by a multidisciplinary team effectively improved the nutriture of patients, promoted the rapid recovery of postoperative gastrointestinal function, reduced postoperative complications, and reduced hospitalization costs.

Long-time follow-up of patients with untreated peripheral T cell lymphoma following chidamide combined with cyclophosphamide, epirubicin, vindesine, prednisone, and etoposide therapy: a single-center propensity score-matching study.

PURPOSE: This is a retrospective, single-center PSM study evaluating the efficacy and safety of chidamide combined with the CHOEP (C-CHOEP) regimen versus the single CHOEP regimen in patients with untreated peripheral T cell lymphomas (PTCL). PATIENTS: Patients newly diagnosed with PTCL between January 2015 and June 2021 were recruited, and were 1:1 divided into C-CHOEP and CHOEP groups according to their first-line chemotherapy regimens. The PSM method was used to match the baseline variables to balance the confounding factors. RESULTS: A cohort of 33 patients each in the C-CHOEP and CHOEP groups was generated after propensity score-matching (PSM). The complete remission (CR) rates of the C-CHOEP regimen were higher than that of the CHOEP regimen (56.3 vs. 25.8%, p = 0.014), whereas the duration of response of the C-CHOEP group was shorter (median DOR 30 vs. 57 months), resulting in roughly similar progression-free survival (PFS) and (overall survival) OS between the two groups. The responding patients who received chidamide maintenance therapy showed a trend of superior PFS and OS compared with patients who did not receive maintenance therapy. CONCLUSIONS: The C-CHOEP regimen was well tolerated but failed to show advantages over the CHOEP regimen in patients with untreated PTCL; however, the chidamide maintenance may contribute to a more durable response and stable long-term survival.

The pattern of alternative splicing and DNA methylation alteration and their interaction in linseed (Linum usitatissimum L.) response to repeated drought stresses.

BACKGROUND: Drought stress has significantly hampered agricultural productivity worldwide and can also result in modifications to DNA methylation levels. However, the dynamics of DNA methylation and its association with the changes in gene transcription and alternative splicing (AS) under drought stress are unknown in linseed, which is frequently cultivated in arid and semiarid regions. RESULTS: We analysed AS events and DNA methylation patterns in drought-tolerant (Z141) and drought-sensitive (NY-17) linseed under drought stress (DS) and repeated drought stress (RD) treatments. We found that the number of intron-retention (IR) and alternative 3' splice site (Alt3'SS) events were significantly higher in Z141 and NY-17 under drought stress. We found that the linseed response to the DS treatment was mainly regulated by transcription, while the response to the RD treatment was coregulated by transcription and AS. Whole genome-wide DNA methylation analysis revealed that drought stress caused an increase in the overall methylation level of linseed. Although we did not observe any correlation between differentially methylated genes (DMGs) and differentially spliced genes (DSGs) in this study, we found that the DSGs whose gene body region was hypermethylated in Z141 and hypomethylated in NY-17 were enriched in abiotic stress response Gene Ontology (GO) terms. This finding implies that gene body methylation plays an important role in AS regulation in some specific genes. CONCLUSION: Our study is the first comprehensive genome-wide analysis of the relationship between linseed methylation changes and AS under drought and repeated drought stress. Our study revealed different interaction patterns between differentially expressed genes (DEGs) and DSGs under DS and RD treatments and differences between methylation and AS regulation in drought-tolerant and drought-sensitive linseed varieties. The findings will probably be of interest in the future. Our results provide interesting insights into the association between gene expression, AS, and DNA methylation in linseed under drought stress. Differences in these associations may account for the differences in linseed drought tolerance.

Hospital Strain and Variation in Sepsis ICU Admission Practices and Associated Outcomes.

To understand how strain-process-outcome relationships in patients with sepsis may vary among hospitals. DESIGN: Retrospective cohort study using a validated hospital capacity strain index as a within-hospital instrumental variable governing ICU versus ward admission, stratified by hospital. SETTING: Twenty-seven U.S. hospitals from 2013 to 2018. PATIENTS: High-acuity emergency department patients with sepsis who do not require life support therapies. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean predicted probability of ICU admission across strain deciles ranged from 4.9% (lowest ICU-utilizing hospital for sepsis without life support) to 61.2% (highest ICU-utilizing hospital for sepsis without life support). The difference in the predicted probabilities of ICU admission between the lowest and highest strain deciles ranged from 9.0% (least strain-sensitive hospital) to 45.2% (most strain-sensitive hospital). In pooled analyses, emergency department patients with sepsis (n = 90,150) experienced a 1.3-day longer median hospital length of stay (LOS) if admitted initially to the ICU compared with the ward, but across the 27 study hospitals (n = 517-6,564), this effect varied from 9.0 days shorter (95% CI, -10.8 to -7.2; p < 0.001) to 19.0 days longer (95% CI, 16.7-21.3; p < 0.001). Corresponding ranges for inhospital mortality with ICU compared with ward admission revealed odds ratios (ORs) from 0.16 (95% CI, 0.03-0.99; p = 0.04) to 4.62 (95% CI, 1.16-18.22; p = 0.02) among patients with sepsis (pooled OR = 1.48). CONCLUSIONS: There is significant among-hospital variation in ICU admission rates for patients with sepsis not requiring life support therapies, how sensitive those ICU admission decisions are to hospital capacity strain, and the association of ICU admission with hospital LOS and hospital mortality. Hospital-level heterogeneity should be considered alongside patient-level heterogeneity in critical and acute care study design and interpretation.

Niclosamide is a potential candidate for the treatment of chemo-resistant osteosarcoma.

Chemotherapy is the main treatment option for advanced osteosarcoma, which is the most common type of primary bone malignancy. However, patients develop resistance rapidly and many succumb to the disease. Niclosamide, an anthelmintic drug, has been recently identified to display potent and selective anti-cancer activity. In this work, we show that niclosamide at sub-micromolar concentrations inhibits proliferation and migration, and induces apoptosis in both parental and chemo-resistant osteosarcoma cells, with much less toxicity in normal osteoblastic cells. Interestingly, chemo-resistant osteosarcoma cells are more sensitive to niclosamide compared to parental cells. We further identify that inhibition of ß-catenin is the underlying mechanism of niclosamide's action in osteosarcoma cells. In addition, we reveal that chemo-resistant osteosarcoma cells display increased ß-catenin activity compared to parental cells, which might explain the hypersensitivity of chemo-resistant cells to niclosamide. Our work provides pre-clinical evidence that niclosamide can be repurposed for treating osteosarcoma. Our findings also suggest the therapeutic value of ß-catenin to overcome osteosarcoma chemo-resistance.

Effect of tinnitus on sound localization ability in patients with normal hearing.

OBJECTIVES: To determine whether tinnitus negatively impacts the accuracy of sound source localization in participants with normal hearing. METHODS: Seventy-five participants with tinnitus and 74 without tinnitus were enrolled in this study. The accuracy of sound source discrimination on the horizontal plane was compared between the two participant groups. The test equipment consisted of 37 loudspeakers arranged in a 180° arc facing forward with 5° intervals between them. The stimuli were pure tones of 0.25, 0.5, 1, 2, 4, and 8kHz at 50dB SPL. The stimuli were divided into three groups: low frequency (LF: 0.25, 0.5, and 1kHz), 2kHz, and high frequency (HF: 4 and 8kHz) stimuli. RESULTS: The Root Mean Square Error (RMSE) score of all the stimuli in the tinnitus group was significantly higher than that in the control group (13.45±3.34 vs. 11.44±2.56, p=4.115, t<0.001). The RMSE scores at LF, 2kHz, and HF were significantly higher in the tinnitus group than those in the control group (LF: 11.66±3.62 vs. 10.04±3.13, t=2.918, p=0.004; 2kHz: 16.63±5.45 vs. 14.43±4.52, t=2.690, p=0.008; HF: 13.42±4.74 vs. 11.14 ±3.68, t=3.292, p=0.001). Thus, the accuracy of sound source discrimination in participants with tinnitus was significantly worse than that in those without tinnitus, despite the stimuli frequency. There was no difference in the ability to localize the sound of the matched frequency and other frequencies (12.86±6.29 vs. 13.87±3.14, t=1.204, p=0.236). Additionally, there was no correlation observed between the loudness of tinnitus and RMSE scores (r=0.096, p=0.434), and the Tinnitus Handicap Inventory (THI) and RMSE scores (r=-0.056, p=0.648). CONCLUSIONS: Our present data suggest that tinnitus negatively impacted sound source localization accuracy, even when participants had normal hearing. The matched pitch and loudness and the impact of tinnitus on patients' daily lives were not related to the sound source localization ability.

Immune suppressive signaling regulated by latent transforming growth factor beta binding protein 1 promotes metastasis in cervical cancer.

Although metastasis is the major cause of death in cervical cancer, the mechanism of metastasis is still unclear. The mRNA expression and protein level of latent transforming growth factor beta binding protein 1 (LTBP1) were detected in tumor tissues and paracancerous tissues from in-house samples. Cell proliferation, cell cycle, migration, and in vivo metastasis were determined after LTBP1 was knocked down. Then, 13 drugs were screened, and the changes in cell apoptosis and proliferation and tumor metastasis were detected after drug treatment in shRNA cells. In our in-house samples, LTBP1 was lowly expressed in cervical cancer tissues. After LTBP1 knockdown, cell proliferation was increased, and the ability of in vitro migration and in vivo metastasis was enhanced. At the same time, the proportion of myeloid derived suppressor cells (MDSC) in situ increased, the proportion of T cells decreased, and transforming growth factor beta-1 (TGFß1) signaling was activated. After carboplatin treatment, LTBP1 shRNA cell line apoptosis increased, metastasis in vivo was limited, and the proportion of MDSC in situ decreased. LTBP1 was lowly expressed in cervical cancer, and the inhibition of LTBP1 can improve the malignant degree of the tumor, and this process can be blocked by carboplatin.