Kanglexin counters vascular smooth muscle cell dedifferentiation and associated arteriosclerosis through inhibiting PDGFR.

BACKGROUND: Dysregulation of vascular smooth muscle cell (VSMC) function leads to a variety of diseases such as atherosclerosis and hyperplasia after injury. However, antiproliferative drug targeting VSMC exhibits poor specificity. Therefore, there is an urgent to develop highly specific antiproliferative drugs to prevention and treatment VSMC dedifferentiation associated arteriosclerosis. Kanglexin (KLX), a new anthraquinone compound designed by our team, has potential to regulate VSMC phenotype according to the physicochemical properties. PURPOSE: This project aims to evaluate the therapeutic role of KLX in VSMC dedifferentiation and atherosclerosis, neointimal formation and illustrates the underlying molecular mechanism. METHODS: In vivo, the ApoE-/- mice were fed with high-fat diet (HFD) for a duration of 13 weeks to establish the atherosclerotic model. And rat carotid artery injury model was performed to establish the neointimal formation model. In vitro, PDGF-BB was used to induce VSMC dedifferentiation. RESULTS: We found that KLX ameliorated the atherosclerotic progression including atherosclerotic lesion formation, lipid deposition and collagen deposition in aorta and aortic sinus in atherosclerotic mouse model. In addition, The administration of KLX effectively ameliorated neointimal formation in the carotid artery following balloon injury in SD rats. The findings derived from molecular docking and surface plasmon resonance (SPR) experiments unequivocally demonstrate that KLX had potential to bind PDGFR-ß. Mechanism research work proved that KLX prevented VSMC proliferation, migration and dedifferentiation via activating the PDGFR-ß-MEK -ERK-ELK-1/KLF4 signaling pathway. CONCLUSION: Collectively, we demonstrated that KLX effectively attenuated the progression of atherosclerosis in ApoE-/- mice and carotid arterial neointimal formation in SD rats by inhibiting VSMC phenotypic conversion via PDGFR-ß-MEK-ERK-ELK-1/KLF4 signaling. KLX exhibits promising potential as a viable therapeutic agent for the treatment of VSMC phenotype conversion associated arteriosclerosis.

Assessment and factors affecting quality of life among patients with Wilson's disease.

Wilson's disease is caused by abnormal copper metabolism resulting in deposition in various organs, including the brain, liver, and cornea, thus disrupting organ function. It is characterized by encephalopathy, extrapyramidal symptoms, progressive liver failure, and copper ring deposition in the cornea. Management of this disease should include quality of life maintenance; however, relevant studies on this topic are lacking. This study aimed to assess the factors affecting the quality of life (QoL) of patients with Wilson's disease. A cross-sectional survey using convenience sampling was conducted between July 2020 and March 2021 at the hospital. Data on patient characteristics, 36-item Short-Form General Health Survey, Uniform Wilson Disease Rating Scale, and Hamilton Depression Rating Scale scores were collected. Associations among quality of life depression, anxiety, and Wilson's disease progression were examined using Pearson correlation analysis. Factors affecting the quality of life of patients, including depression, anxiety, liver function, clinical symptoms, diet, liver function, brain magnetic resonance imaging (MRI) findings, disease duration, Barthel Index, and Morse scores were examined using multivariate linear regression analysis. This study included 134 patients with Wilson's disease whose mean age was 29.12 ± 8.59 years. The mean QoL score in the patient group was 71.38 ± 9.55 points and was negatively correlated with anxiety (r = - 0.883, P = 0.000), depression (r = - 0.852 P = 0.000), and clinical symptoms (r = - 0.542, P = 0.000) scores. Anxiety, depression, and clinical symptoms severity are vital factors for the QoL of patients with Wilson's disease. The study provides foundational evidence to design novel interventions, including symptom management, diet, and self-care ability, which can help in improving the quality of life in patients with Wilson's disease and decreasing the burden associated with this disease.

Safety of Ambulatory Surgery For Obstructive Sleep Apnea: A Retrospective Review.

OBJECTIVE: Assess the safety of ambulatory surgery performed for obstructive sleep apnea. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care hospital. METHODS: Demographic data including age, gender, race, body mass index, insurance status, socioeconomic status, and distance traveled for surgery was collected, as well as comorbidities, and apnea-hypopnea index (AHI). Outcome variables included continuous positive airway pressure reinitiation, planned/unplanned postoperative admission, emergency department (ED) presentation, or readmission within 7 and 14 days of surgery. RESULTS: A total of 601 patients were included, who underwent sleep surgery between 2017 and 2022. The median age was 55 years [interquartile range: 19]. A total of 437 patients (73%) were male, 502 (84%) were Caucasian, and the median distance traveled was 20 miles [27]. The median AHI was 27.1 [26]. A total of 286 hypoglossal nerve stimulators, 12 tonsillectomies, 160 expansion sphincteroplasties (ESP), and 201 nasal procedures were performed. There were 9 (1%) planned and 23 (4%) total admissions postoperatively. Sixteen patients (2%) presented to ED within 7 days, and 22 (3%) within 14 days. Nine (1%) were readmitted within 7 days, and 12 (2%) within 14 days. There were significantly more planned admissions, unplanned admissions, ED presentations, and readmissions for ESP. There were no significant differences in demographic or clinical data between patients who underwent single versus multiple surgeries. CONCLUSION: Outpatient sleep surgery is generally safe. Close postoperative monitoring is necessary and overnight observation should be considered in those with very severe sleep apnea and/or significant comorbidities. The distance a patient travels should also be considered for overnight admission.

Association of Mutant KRAS Alleles With Morphology and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma.

CONTEXT.­: Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood. OBJECTIVE.­: To characterize the potential morphologic and clinical outcome differences in PDACs harboring distinct mutant KRAS alleles. DESIGN.­: Cohort 1 consisted of 127 primary conventional PDACs with no neoadjuvant therapy, excluding colloid/mucinous, adenosquamous, undifferentiated, and intraductal papillary mucinous neoplasm-associated carcinomas, for which an in-house 42-gene mutational panel had been performed. A morphologic classification system was devised wherein each tumor was assigned as conventional, papillary/large duct (P+LD, defined as neoplastic glands with papillary structure and/or with length ≥0.5 mm), or poorly differentiated (when the aforementioned component was 60% or more of the tumor). Cohort 2 was a cohort of 88 PDACs in The Cancer Genome Atlas, which were similarly analyzed. RESULTS.­: In both cohorts, there was significant enrichment of P+LD morphology in PDACs with KRAS G12V and G12R compared with G12D. In the entire combined cohort, Kaplan-Meier analyses showed longer overall survival (OS) with KRAS G12R as compared with G12D (median OS of 1255 versus 682 days, P = .03) and in patients whose PDACs displayed P+LD morphology as compared with conventional morphology (median OS of 1175 versus 684 days, P = .04). In the adjuvant-only subset, KRAS G12R had the longest OS compared with G12D, G12V, and other alleles (median OS unreached/undefined versus 1009, 1129, and 1222 days, respectively). CONCLUSIONS.­: PDACs with different mutant KRAS alleles are associated with distinct morphologies and clinical outcomes, with KRAS G12R allele associated with P+LD morphology and longer OS when compared with G12D using Kaplan-Meier studies.

Bidirectional pharmacokinetics of doravirine, tenofovir, and feminizing hormones in transgender women (IDentify): A randomized crossover trial.

Transgender women may have concerns of drug interactions between feminizing hormone therapy (FHT) and antiretrovirals, leading to nonadherence. This randomized, three-period crossover, open-label, phase I trial assessed the effects of doravirine (DOR) and tenofovir disoproxil fumarate (TDF) on the pharmacokinetics (PKs) of estradiol, spironolactone, and total testosterone and vice versa in healthy transgender women. Volunteers were randomized 1:1 into two sequences containing three treatment groups (DOR, lamivudine [3TC], and TDF alone; estradiol, spironolactone, and placebo; and DOR/3TC/TDF, estradiol, and spironolactone). Eight subjects enrolled in the study and six had completed all study periods. The geometric mean ratios for DOR area under the concentration-time curve from zero to last measured concentration (AUC0-last ), maximum concentration (Cmax ), and concentration at 24 h (C24 ) were similar. However, tenofovir (TFV) AUC0-last , Cmax , and C24 moderately increased by 14%-38%. Last, estradiol AUC0-last , Cmax , and C24 were increased by 10%-13%. Whereas most 90% confidence intervals did not meet the bioequivalence bounds of 80%-125%, the point estimates fell within the intervals. Log-transformed DOR, TFV, and estradiol PK parameters computed with and without co-administration were not statistically different (p > 0.05). There were no serious adverse events. There is not a clinically significant impact of FHT on DOR/TFV PKs. Similarly, there is no observed impact on estradiol PKs and total testosterone following use of DOR/3TC/TDF.

Social appearance anxiety among the dark tetrad and self-concealment.

This study analyzed the effects of the Dark Tetrad (narcissism, Machiavellianism, psychopathy, sadism) and self-concealment on social appearance anxiety. Empirical investigations on which personality traits influence social appearance anxiety are yet missing. In this study, a sample of N = 1186 Chinese students performed a questionnaire-based survey assessing different personality facets and social appearance anxiety tendencies. Measures included the Narcissistic Personality Inventory, the Levenson Self-Report Psychopathy Scale, the Machiavellian Personality Scale, the Short Sadistic Impulse Scale, the Self-concealment Scale, and the Social Appearance Anxiety Scale. The results of the multiple regression analysis showed that psychopathy, Machiavellianism, sadism, and self-concealment positively predicted social appearance anxiety and narcissism negatively predicted social appearance anxiety. Machiavellianism, psychopathy, sadism, and self-concealment were positive predictors of social appearance anxiety, whereas narcissism was a negative predictor. These findings provide insight into the complex nature of the Dark Tetrad and their influence on social appearance anxiety.

Myeloid-derived growth factor suppresses VSMC dedifferentiation and attenuates postinjury neointimal formation in rats by activating S1PR2 and its downstream signaling.

Restenosis after angioplasty is caused usually by neointima formation characterized by aberrant vascular smooth muscle cell (VSMC) dedifferentiation. Myeloid-derived growth factor (MYDGF), secreted from bone marrow-derived monocytes and macrophages, has been found to have cardioprotective effects. In this study we investigated the effect of MYDGF to postinjury neointimal formation and the underlying mechanisms. Rat carotid arteries balloon-injured model was established. We found that plasma MYDGF content and the level of MYDGF in injured arteries were significantly decreased after balloon injury. Local application of exogenous MYDGF (50 µg/mL) around the injured vessel during balloon injury markedly ameliorated the development of neointimal formation evidenced by relieving the narrow endovascular diameter, improving hemodynamics, and reducing collagen deposition. In addition, local application of MYDGF inhibited VSMC dedifferentiation, which was proved by reversing the elevated levels of osteopontin (OPN) protein and decreased levels of α-smooth muscle actin (α-SMA) in the left carotid arteries. We showed that PDGF-BB (30 ng/mL) stimulated VSMC proliferation, migration and dedifferentiation in vitro; pretreatment with MYDGF (50-200 ng/mL) concentration-dependently eliminated PDGF-BB-induced cell proliferation, migration and dedifferentiation. Molecular docking revealed that MYDGF had the potential to bind with sphingosine-1-phosphate receptor 2 (S1PR2), which was confirmed by SPR assay and Co-IP analysis. Pretreatment with CCG-1423 (Rho signaling inhibitor), JTE-013 (S1PR2 antagonist) or Ripasudil (ROCK inhibitor) circumvented the inhibitory effects of MYDGF on VSMC phenotypic switching through inhibiting S1PR2 or its downstream RhoA-actin monomers (G-actin) /actin filaments (F-actin)-MRTF-A signaling. In summary, this study proves that MYDGF relieves neointimal formation of carotid arteries in response to balloon injury in rats, and suppresses VSMC dedifferentiation induced by PDGF-BB via S1PR2-RhoA-G/F-actin-MRTF-A signaling pathway. In addition, our results provide evidence for cross talk between bone marrow and vasculature.

Prednisone Decreases Opioid Use in Adults Undergoing Benign Oropharyngeal Surgery.

OBJECTIVE: This study sought to analyze the efficacy and safety of postoperative prednisone to reduce reliance on opioids in adult benign oropharyngeal surgery. STUDY DESIGN: Prospective cohort study. SETTING: Single tertiary-care facility. METHODS: Patients undergoing tonsillectomy (T), tonsillectomy and adenoidectomy (T&A), and/or modified uvulopalatopharyngoplasty (UPPP) from December 2020 to January 2023 received the standard of care postoperative management. A prednisone taper was dependent on surgeon preference. Cohorts were based on the prescription of postoperative steroids. Patients completed a survey to assess opioid usage, pain scores, and steroid compliance. RESULTS: Seventy-two patients were included. The nonsteroid cohort (N = 29) received an average of 467 ± 94.1 morphine milligram equivalents (MME), and the steroid cohort (N = 43) received an average of 285 ± 128 MME (P < 0.001). The nonsteroid cohort consumed 1.62 times more opioids than the steroid cohort (P < 0.002). There were no significant differences in complication or refill rates between treatment groups. There were no significant differences in pain scores on the day of surgery or postoperative days 1, 5, or 10 (P = 0.34, P = 0.66, P = 0.62, and P = 0.22, respectively). Patients undergoing T&A (p = 0.019) or who had current psychiatric medication use (P < 0.006) consumed significantly more opioids. Patients who received a total opioid prescription of >300 MME (40 5-mL doses of 5 mg/5 mL liquid oxycodone) consumed 2.27 times more postoperative opioids than patients with opioid prescriptions ≤300 MME (P < 0.001). CONCLUSION: Patients who did not receive steroids consumed 1.62 times more postoperative opioids compared to those who completed a steroid taper. Corticosteroid use was not associated with changes in pain scores, refill rates, or complication rates and may be considered in a multimodal approach to pain management in adults undergoing benign oropharyngeal surgery, although further study is warranted.

Feasibility of a Text Messaging-Integrated and Chatbot-Interfaced Self-Management Program for Symptom Control in Patients With Gastrointestinal Cancer Undergoing Chemotherapy: Pilot Mixed Methods Study.

BACKGROUND: Outpatient chemotherapy often leaves patients to grapple with a range of complex side effects at home. Leveraging tailored evidence-based content to monitor and manage these symptoms remains an untapped potential among patients with gastrointestinal (GI) cancer. OBJECTIVE: This study aims to bridge the gap in outpatient chemotherapy care by integrating a cutting-edge text messaging system with a chatbot interface. This approach seeks to enable real-time monitoring and proactive management of side effects in patients with GI cancer undergoing intravenous chemotherapy. METHODS: Real-Time Chemotherapy-Associated Side Effects Monitoring Supportive System (RT-CAMSS) was developed iteratively, incorporating patient-centered inputs and evidence-based information. It synthesizes chemotherapy knowledge, self-care symptom management skills, emotional support, and healthy lifestyle recommendations. In a single-arm 2-month pilot study, patients with GI cancer undergoing chemotherapy received tailored intervention messages thrice a week and a weekly Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events-based symptom assessment via a chatbot interface. Baseline and postintervention patient surveys and interviews were conducted. RESULTS: Out of 45 eligible patients, 34 were enrolled (76% consent rate). The mean age was 61 (SD 12) years, with 19 (56%) being females and 21 (62%) non-Hispanic White. The most common cancer type was pancreatic (n=18, 53%), followed by colon (n=12, 35%) and stomach (n=4, 12%). In total, 27 (79% retention rate) participants completed the postintervention follow-up. In total, 20 patients texted back at least once to seek additional information, with the keyword "chemo" or "support" texted the most. Among those who used the chatbot system checker, fatigue emerged as the most frequently reported symptom (n=15), followed by neuropathy (n=7). Adjusted for multiple comparisons, patients engaging with the platform exhibited significantly improved Patient Activation Measure (3.70, 95% CI -6.919 to -0.499; P=.02). Postintervention interviews and satisfaction surveys revealed that participants found the intervention was user-friendly and were provided with valuable information. CONCLUSIONS: Capitalizing on mobile technology communication holds tremendous scalability for enhancing health care services. This study presents initial evidence of the engagement and acceptability of RT-CAMSS, warranting further evaluation in a controlled clinical trial setting.

Microlens-Assisted Light-Scattering Imaging of Plasmonic Nanoparticles at the Single Particle Level.

We present a microlens-assisted imaging approach to record the scattering light of plasmonic nanoparticles at the single particle level. The microlens can significantly enhance the backscattering of visible light from individual plasmonic nanoparticles by several dozen folds, and single gold nanoparticles with a diameter as low as 60 nm can be imaged under a conventional optical microscope. This can benefit from a significant increase in the scattering intensity afforded by the microlens, meaning that the imaging of gold nanoparticles at a high temporal resolution (up to 5000 Hz) can be achieved, which is fast enough to record single particle adhesion events on the substrate. This research presents a fast and efficient means of acquiring scattering light from plasmonic nanoparticles, which has great potential to develop plasmonic nanoparticle-based biosensors and investigate a wide range of plasmonic nanoparticle-based fast interaction processes.

Comparison of outcomes of an 18-gauge vs 16-gauge ultrasound-guided percutaneous renal biopsy: a systematic review and meta-analysis.

Background: The needle size used in ultrasound-guided percutaneous renal biopsy significantly influences the efficacy and safety of the procedure. The aim of this study is to perform a comparative analysis of 16-gauge and 18-gauge needles for ultrasound-guided percutaneous renal biopsy.Methods: This systematic review and meta-analysis included randomized controlled trials and observational studies that compared the outcomes of using 18-gauge and 16-gauge needles for ultrasound-guided percutaneous renal biopsy. The efficacy parameters included a mean number of glomeruli obtained and the number of passes, while the safety parameters focused on the rate of complications. We searched multiple databases, assessed the risk of bias, and conducted statistical analyses using appropriate models.Results: Fifteen studies were included. Compared to the 18-gauge needle, the use of 16-gauge needle for the biopsy was associated with the significantly higher mean number of glomeruli obtained (pooled SMD 0.61, 95%CI: 0.32 to 0.89; p < 0.001) and fewer required passes (pooled SMD -0.57, 95%CI: -0.97 to -0.18; p = 0.004). No significant difference was observed in the individual safety parameters, including pain, hematuria, need for blood transfusion, major, and minor complications. However, the use of 16-gauge needle was associated with higher odds of total complications (pooled OR 1.57, 95%CI: 1.16 to 2.13; p = 0.004).Conclusion: While the 16-gauge needle for ultrasound-guided percutaneous renal biopsy offers improved efficacy in terms of a higher mean number of glomeruli and fewer required passes, it is associated with higher total complications. A judicious needle size selection that would consider patient-specific factors and risk-benefit ratio, is crucial for optimizing patient outcomes.

Selection of optimal quantile protein biomarkers based on cell-level immunohistochemistry data.

BACKGROUND: Protein biomarkers of cancer progression and response to therapy are increasingly important for improving personalized medicine. Advanced quantitative pathology platforms enable measurement of protein expression in tissues at the single-cell level. However, this rich quantitative cell-by-cell biomarker information is most often not exploited. Instead, it is reduced to a single mean across the cells of interest or converted into a simple proportion of binary biomarker-positive or -negative cells. RESULTS: We investigated the utility of retaining all quantitative information at the single-cell level by considering the values of the quantile function (inverse of the cumulative distribution function) estimated from a sample of cell signal intensity levels in a tumor tissue. An algorithm was developed for selecting optimal cutoffs for dichotomizing cell signal intensity distribution quantiles as predictors of continuous, categorical or survival outcomes. The proposed algorithm was used to select optimal quantile biomarkers of breast cancer progression based on cancer cells' cell signal intensity levels of nuclear protein Ki-67, Proliferating cell nuclear antigen, Programmed cell death 1 ligand 2, and Progesterone receptor. The performance of the resulting optimal quantile biomarkers was validated and compared to the standard cancer compartment mean signal intensity markers using an independent external validation cohort. For Ki-67, the optimal quantile biomarker was also compared to established biomarkers based on percentages of Ki67-positive cells. For proteins significantly associated with PFS in the external validation cohort, the optimal quantile biomarkers yielded either larger or similar effect size (hazard ratio for progression-free survival) as compared to cancer compartment mean signal intensity biomarkers. CONCLUSION: The optimal quantile protein biomarkers yield generally improved prognostic value as compared to the standard protein expression markers. The proposed methodology has a broad application to single-cell data from genomics, transcriptomics, proteomics, or metabolomics studies at the single cell level.

Predictors of opioid requirement among patients receiving free flap reconstruction to the head and neck.

BACKGROUND: Opioids are a part of standard of care treatment of acute, severe postoperative pain. However, increased opioid requirements have been shown to be associated with increased postoperative complications, morbidity, and mortality. The aim of this study was to identify potential predictive factors associated with increased or decreased opioid requirements after free tissue transfer (FTT) to the head and neck. MATERIALS/METHODS: A retrospective review was conducted on subjects who underwent head and neck reconstruction (HNR) from 2015 to 2021 at a single tertiary care center. Patients with inpatient stay over 10 days and those receiving fentanyl for sedation purposes were excluded due to EMR limitations and confounding, respectively. The total dose of opioid medication each patient received was calculated and summed using morphine milligram equivalents (MME). Statistical analysis was conducted using poisson regression and multivariable regression models. RESULTS: Two hundred and ninety-one patients were included. The mean opioid requirement for all subjects was 228.6 (SD 250.0) MMEs during their entire postoperative stay and the mean length of stay was 6.0 (SD 1.7) days. An established opioid prescription prior to surgical resection was the greatest predictor of increased risk for opioid requirement according univariate and multivariate analysis 2.356 (2.321-2.392), p ≤ 0.0001 and 1.833 (1.802-1.863), p ≤ 0.0001, respectively. Fibula transfers were associated with higher opioid requirements while scapula transfers were associated with decreased opioid requirements compared to other free tissue transfer types. CONCLUSION: Preoperative opioid use was associated with higher postoperative opioid requirements. Multimodal pain management (MMPM) was not associated with a decreased opioid requirement; however, further studies are needed to investigate the hierarchy, dosing, and timing of MMPM in relation to opioid requirements and pain control.

A novel small molecule AdipoR2 agonist ameliorates experimental hepatic steatosis in hamsters and mice.

Adiponectin receptor 2 (AdipoR2) can be activated by its endogenous ligand adiponectin to reduce hepatic steatosis, and is regarded as a therapeutic target for metabolic associated fatty liver disease (MAFLD). This study proposes a novel anthraquinone compound, emodin succinate monoethyl ester (ESME), which activates AdipoR2, inhibits hepatic lipogenesis, promotes fatty acid oxidation, and alleviates experimental hepatic steatosis in hamsters and mice. Molecular docking shows that ESME has strong binding potential with AdipoR2 by forming a arene-arene interaction. AdipoR2 on the cytomembrane of HepG2 cells can be labeled by fluorescent ESME (Cy5-ESME). ESME activates AdipoR2, AMPK and PPARα, and reduces lipid deposition in palmitic acid or oleic acid-induced HepG2 and L02 cells. Suppression of AdipoR2 expression or AMPK activation completely eliminates the effect of ESME on reducing lipid accumulation in hepatocytes. Oral administration of ESME reduces liver lipid production and accumulation, and alleviates hepatic steatosis in hamsters and Apoe-/- mice induced by high-fat diet. Compared with statins and emodin, ESME showed prepotent efficacy and safety in reducing hepatic steatosis and protecting hepatocytes. Furthermore, ESME activates CaMKK2 and LKB1 in liver to activate AMPK and reduce lipogenesis through stimulating AdipoR2. Taken together, ESME reduces hepatic lipid accumulation and alleviates hepatic steatosis by agonizing AdipoR2. ESME is a promising new agent for clinical treatment of MAFLD.

Quantile Index Biomarkers Based on Single-Cell Expression Data.

Current histocytometry methods enable single-cell quantification of biomolecules in tumor tissue sections by multiple detection technologies, including multiplex fluorescence-based immunohistochemistry or in situ hybridization. Quantitative pathology platforms can provide distributions of cellular signal intensity (CSI) levels of biomolecules across the entire cell populations of interest within the sampled tumor tissue. However, the heterogeneity of CSI levels is usually ignored, and the simple mean signal intensity value is considered a cancer biomarker. Here we consider the entire distribution of CSI expression levels of a given biomolecule in the cancer cell population as a predictor of clinical outcome. The proposed quantile index (QI) biomarker is defined as the weighted average of CSI distribution quantiles in individual tumors. The weight for each quantile is determined by fitting a functional regression model for a clinical outcome. That is, the weights are optimized so that the resulting QI has the highest power to predict a relevant clinical outcome. The proposed QI biomarkers were derived for proteins expressed in cancer cells of malignant breast tumors and demonstrated improved prognostic value compared with the standard mean signal intensity predictors. The R package Qindex implementing QI biomarkers has been developed. The proposed approach is not limited to immunohistochemistry data and can be based on any cell-level expressions of proteins or nucleic acids.

TOMM20 as a Potential Prognostic Biomarker in Chordoma: Results From a High-Volume, Single-Center Study.

OBJECTIVES: As few large studies identify correlative biomarkers in chordoma, our objective was to use our large, single-center chordoma tumor bank to identify novel signaling pathways. METHODS: Clinical and pathologic data for 73 patients with chordoma were retrospectively collected. Tumor microarrays were built from 61 archived chordoma specimens; immunohistochemistry for TOMM20, TIGAR, and MCT1 were performed; and semiquantitative analysis of staining intensity and percentage of positive tumor cells was performed. Average composite scores of MCT1, TIGAR, and TOMM20 expression were compared by disease status and anatomic location. RESULTS: Higher expression of TOMM20 was seen in recurrent and metastatic chordomas compared with primary lesions. Comparing composite scores of primary lesions in patients with primary disease only vs those with recurrent disease showed that TIGAR and TOMM20 expressions are significantly higher in primary lesions, followed by a history of recurrence. A TOMM20 composite score of greater than or equal to 3 significantly decreased overall survival (hazard ratio [HR], 5.83) and recurrence-free survival (HR, 8.95). CONCLUSIONS: Identifying novel signaling pathways that promote chordoma growth and recurrence is critical for developing targeted therapy for chordoma. TOMM20 may be a biomarker associated with chordoma disease progression.

Master of nursing specialist experiences of an internship through the use of written reflections: A qualitative research study.

Background: Reflective practice is an educational strategy and an essential part of the professional development of nurses. However, there are few reflective journals in the master of nursing specialist program or clinical nursing education. Objectives: Based on Gibbs' reflective cycle theory, masters of nursing specialists (MNS) will use a diary to record their reflections on a particular clinical event. The purpose of this study was to identify reflective practice as tool to help MNS improve their professional and personal development. Design: A descriptive qualitative study. Methods: The purposive sampling method was used in the qualitative study. The data were derived from the master of nursing specialist who interned at the hospital from June to December 2021. After completing the job rotation and relevant course training within 6 months, a clinical experience was selected as a reflection. The traditional qualitative content analysis method was applied to analyze the collected data in the research. Results: A total of 10 reflective diaries completed by ten students were analyzed. This qualitative study demonstrated that the Gibbs' reflective cycle is valuable and helpful in the clinical practice of master of nursing specialists. This program helps master of nursing specialists reflect on their clinical practice and translate real-life experiences into valuable learning experiences for developing their professional development and personal skills. Conclusions: By writing reflection diaries, master of nursing specialists can reflect on the problems encountered during clinical rotations and take action following that reflection, which can assist them in improving their professional development and personal skills to handle clinical nursing aspects in the future, as well as improve their full participation in clinical practice.