Clinicopathologic and molecular correlates to neoadjuvant chemotherapy-induced pathologic response in breast angiosarcoma.

Both primary and secondary breast angiosarcoma (AS) are characterized by multifocal presentation and aggressive behavior. Despite multimodality therapy, local and distant relapse rates remain high. Therefore, neoadjuvant chemotherapy (NACT) is employed to improve the R0 resection rates and survival, but its benefits remain controversial. Herein, we investigate pathologic and molecular correlates to NACT-induced histologic response in a group of 29 breast AS, 4 primary and 25 radiation-associated (RA). The two NACT regimens applied were anthracycline- and non-anthracycline-based. The pathologic response grade was defined as: I: ≤ 50%, II: 51%-90%, III: 91%-99%, and IV: 100%. An additional 45 primary AS and 102 RA-AS treated by surgery alone were included for survival comparison. The genomic landscape was analyzed in a subset of cases and compared to a cohort of AS without NACT on a paired tumor-normal targeted DNA NGS platform. All patients were females, with a median age of 31 years in primary AS and 68 years in RA-AS. All surgical margins were negative in NACT group. The NACT response was evenly divided between poor (Grades I-II; n = 15) and good responders (Grades III-IV; n = 14). Mitotic count >10/mm2 was the only factor inversely associated with pathologic response. By targeted NGS, all 10 post-NACT RA-AS demonstrated MYC amplification, while both primary AS harbored KDR mutations. TMB or other genomic alterations did not correlate with pathologic response. All four patients with Grade IV response remained free of disease. The good responders had a significantly better disease-specific survival (p = 0.04). There was no survival difference with NACT status or the NACT regimens applied. However, NACT patients with MYC-amplified tumors showed better disease-free survival (p = 0.04) compared to MYC-amplified patients without NACT. The overall survival of NACT group correlated with size >10 cm (p = 0.02), pathologic response (p = 0.04), and multifocality (p = 0.01) by univariate, while only size >10 cm (p = 0.03) remained significant by multivariate analysis.

Sarcomas With RAD51B Fusions Are Associated With a Heterogeneous Phenotype.

RAD51B-rearranged sarcomas are rare neoplasms that exhibit a heterogeneous morphology. To date, 6 cases have been reported, all involving the uterus, including 4 perivascular epithelioid cell tumors (PEComas) and 2 leiomyosarcomas (LMS). In this study, we describe the morphologic, immunohistochemical, and molecular features of 8 additional sarcomas with RAD51B rearrangement, including the first extrauterine example. All patients were women with a median age of 57 years at presentation. Seven tumors originated in the uterus, and one in the lower extremity soft tissue, with a median tumor size of 12 cm. Histologically, 4 tumors showed predominantly spindle cell morphology with eosinophilic fibrillary cytoplasm, with or without nuclear pleomorphism, whereas 2 tumors exhibited pleomorphic epithelioid cells, featuring clear to eosinophilic, granular cytoplasm. Two neoplasms exhibited undifferentiated cytomorphology, including one with uniform small blue round cells. All tumors showed high-grade cytologic atypia and high mitotic activity (median: 30/10 high-power fields), whereas coagulative necrosis was noted in 6 cases and lymphovascular invasion in 2. By immunohistochemistry, 2 showed myoid and melanocytic markers in keeping with PEComa, whereas 4 cases were only positive for smooth muscle markers consistent with LMS (including 3 myxoid). The remaining 2 cases had a nonspecific immunoprofile. Five cases tested by targeted RNA sequencing (Archer FusionPlex, Illumina TruSight) showed different fusion partners (HMGA2, PDDC1, and CEP170). RAD51B rearrangements were identified by FISH in the remaining 3 cases. Targeted DNA sequencing in 2 cases was negative for TSC gene alterations. Clinical outcome, available in 5 patients (median follow-up, 19 months), revealed 3 local recurrences, 2 lung metastases, and 4 deaths due to disease. Our results expand the spectrum of sarcomas with RAD51B fusions, demonstrating variable clinical presentations, morphologic spectrum, and fusion partners. These tumors have a predilection for a uterine location, with either LMS, PEComa, or undifferentiated phenotypes, and are associated with an aggressive clinical course.

Hinokitiol Inhibits Breast Cancer Cells In Vitro Stemness-Progression and Self-Renewal with Apoptosis and Autophagy Modulation via the CD44/Nanog/SOX2/Oct4 Pathway.

Breast cancer (BC) represents one of the most prevalent malignant threats to women globally. Tumor relapse or metastasis is facilitated by BC stemness progression, contributing to tumorigenicity. Therefore, comprehending the characteristics of stemness progression and the underlying molecular mechanisms is pivotal for BC advancement. Hinokitiol (ß-thujaplicin), a tropolone-related compound abundant in the heartwood of cupressaceous plants, exhibits antimicrobial activity. In our study, we employed three BC cell lines (MDA-MB-231, MCF-7, and T47D) to assess the expression of stemness-, apoptosis-, and autophagy-related proteins. Hinokitiol significantly reduced the viability of cancer cells in a dose-dependent manner. Furthermore, we observed that hinokitiol enhances apoptosis by increasing the levels of cleaved poly-ADP-ribose polymerase (PARP) and phospho-p53. It also induces dysfunction in autophagy through the upregulation of LC3B and p62 protein expression. Additionally, hinokitiol significantly suppressed the number and diameter of cancer cell line spheres by reducing the expression of cluster of differentiation44 (CD44) and key transcription factors. These findings underscore hinokitiol's potential as a therapeutic agent for breast cancer, particularly as a stemness-progression inhibitor. Further research and clinical studies are warranted to explore the full therapeutic potential of hinokitiol in the treatment of breast cancer.

Isolation of Acetylated and Unmodified Protein N-Terminal Peptides by Strong Cation Exchange Chromatographic Separation of TrypN-Digested Peptides.

We developed a simple and rapid method to enrich protein N-terminal peptides, in which the protease TrypN is first employed to generate protein N-terminal peptides without Lys or Arg and internal peptides with two positive charges at their N termini, and then, the N-terminal peptides with or without N-acetylation are separated from the internal peptides by strong cation exchange chromatography according to a retention model based on the charge/orientation of peptides. This approach was applied to 20 µg of human HEK293T cell lysate proteins to profile the N-terminal proteome. On average, 1550 acetylated and 200 unmodified protein N-terminal peptides were successfully identified in a single LC/MS/MS run with less than 3% contamination with internal peptides, even when we accepted only canonical protein N termini registered in the Swiss-Prot database. Because this method involves only two steps, protein digestion and chromatographic separation, without the need for tedious chemical reactions, it should be useful for comprehensive profiling of protein N termini, including proteoforms with neo-N termini.

Quantitative Proteomic Analysis on the Slightly Acidic Electrolyzed Water Triggered Viable but Non-Culturable Listeria monocytogenes.

This study undertakes a comprehensive exploration of the impact of slightly acidic electrolyzed water (SAEW) on Listeria monocytogenes, a common foodborne pathogen, with a particular focus on understanding the molecular mechanisms leading to the viable but nonculturable (VBNC) state. Given the widespread application of SAEW as an effective disinfectant in the food industry, uncovering these molecular pathways is crucial for improving food safety measures. We employed tandem mass tags (TMT), labeling proteomic techniques and LC-MS/MS to identify differentially expressed proteins under two doses of SAEW conditions. We indicated 203 differential expressed proteins (DEPs), including 78 up-regulated and 125 down-regulated DEPs. The functional enrichment analysis of these proteins indicated that ribosomes, biosynthesis of secondary metabolites, and aminoacyl-tRNA biosynthesis were enriched functions affected by SAEW. Further, we delved into the role of protein chlorination, a potential consequence of reactive chlorine species generated during the SAEW production process, by identifying 31 chlorinated peptides from 22 proteins, with a dominant sequence motif of Rxxxxx[cY] and functionally enriched in translation. Our findings suggest that SAEW might prompt alterations in the protein translation process and trigger compensatory ribosome biosynthesis. However, an imbalance in the levels of elongation factors and AARSs could hinder recovery, leading to the VBNC state. This research carries substantial implications for food safety and sanitation, as it adds to our understanding of the SAEW-induced VBNC state in L. monocytogenes and offers potential strategies for its control.

Self-report instruments for measuring patient dignity: A psychometric systematic review.

AIMS: To synthesize and evaluate the psychometric properties of self-report instruments that measure patient dignity. DESIGN: A psychometric systematic review. DATA SOURCES: A comprehensive search of studies published from inception until February 17, 2022, was performed using PubMed, Embase, CINAHL, Web of Science, and Scopus. REVIEW METHODS: The methodological quality of the psychometric studies was evaluated following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines. RESULTS: Eleven self-report instruments that evaluate dignity were identified. For most instruments, psychometric properties, including reliability, cross-cultural validity, responsiveness, and measurement error, had not been adequately examined. The Patient Dignity Inventory (PDI), the Jacelon's Attributed Dignity Scale (JADS), and the Inpatient Dignity Scale (IPDS) had acceptable content validity, structure validity, and internal consistency to measure dignity among adult patients under palliative care, community-dwelling older adults, and inpatients receiving daily care. CONCLUSION: The PDI, the JADS, and the IPDS are recommended for future clinical practice and research to measure dignity among adult patients under palliative care, community-dwelling older adults, and inpatients receiving daily care. Early identification of patients' dignity-related problems in nursing care can prevent negative health outcomes and help develop a timely intervention to promote patients' health and recovery. IMPACT: Given that the psychometric properties of the existing self-report dignity instruments have not been systematically assessed, the present review utilized comprehensive methods according to COSMIN to evaluate and determine the most appropriate measure for research and practice. The PDI, the JADS, and the IPDS demonstrated satisfactory psychometric properties and are, thus, recommended for clinical and research applications. Nursing professionals can employ these instruments to assess and promptly identify dignity issues among both young and older adults in hospitals and communities.

Quantitative Proteome Analysis Reveals Melissa officinalis Extract Targets Mitochondrial Respiration in Colon Cancer Cells.

Melissa officinalis (MO), known as lemon balm, is a popular ingredient blended in herbal tea. In recent decades, the bioactivities of MO have been studied in sub-health and pathological status, highlighting MO possesses multiple pharmacological effects. We previously showed that hot water MO extract exhibited anticancer activity in colorectal cancer (CRC). However, the detailed mechanisms underlying MO-induced cell death remain elusive. To elucidate the anticancer regulation of MO extract in colon cancer, a data-driven analysis by proteomics approaches and bioinformatics analysis was applied. An isobaric tandem mass tags-based quantitative proteome analysis using liquid chromatography-coupled tandem mass spectrometry was performed to acquire proteome-wide expression data. The over-representation analysis and functional class scoring method were implemented to interpret the MO-induced biological regulations. In total, 3465 quantifiable proteoforms were identified from 24,348 peptides, with 67 upregulated and 54 downregulated proteins in the MO-treated group. Mechanistically, MO impeded mitochondrial respiratory electron transport by triggering a reactive oxygen species (ROS)-mediated oxidative stress response. MO hindered the mitochondrial membrane potential by reducing the protein expression in the electron transport chain, specifically the complex I and II, which could be restored by ROS scavenger. The findings comprehensively elucidate how MO hot water extract activates antitumor effects in colorectal cancer (CRC) cells.

Adlay Seed (Coix lacryma-jobi L. var. Ma-yuen Stapf.) Ethanolic Extract Fractions and Subfractions Induce Cell Cycle Arrest and Apoptosis in Human Breast and Cervical Cancer Cell Lines.

The antitumor effects of Coix lacryma-jobi L. var. ma-yuen Stapf. (adlay seed) ethanolic extract have been increasingly shown. This study aimed to investigate the beneficial effects of both the fractions and subfractions of adlay seed ethanolic extract on the human breast (MCF-7) and cervical (HeLa) cancer cell lines, as well as exploring their possible mechanisms of action. The ethanolic extracts were obtained from different parts of adlay seed, including AHE (adlay hull extract), ATE (adlay testa extract), ABE (adlay bran extract) and PAE (polished adlay extract). The results of a 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl- tetrazolium bromide (MTT) assay showed that AHE-Ea and ATE-Ea showed significant growth inhibitory effects in a dose-dependent manner. The results also showed that the AHE-Ea-K, AHE-Ea-L, ATE-Ea-E and ATE-Ea-F subfractions inhibited cell proliferation, induced cell cycle arrest in the G0/G1 phase and decreased CDK4/Cyclin D1 protein expression. Finally, the extract activated caspase-3 activity and PARP protein expression, which induced MCF-7 and HeLa cell apoptosis. We then used liquid chromatography-mass spectrometry (LC/MS) to identify the potential active components., Quercetin showed an anticancer capacity. In conclusion, the AHE-Ea-K, AHE-Ea-L, ATE-Ea-E and ATE-Ea-F subfractions showed antitumor effects through the inhibition of MCF-7 and HeLa cell line viability, as well as inducing apoptosis and cell cycle arrest.

Appraisal and evaluation of the instruments measuring the nursing work environment: A systematic review.

AIMS: To appraise the current instruments available for measuring the nursing work environment and re-examine the definition and construct of the nursing work environment. BACKGROUND: A psychometrically sound instrument is fundamental to understanding and improving the nursing work environment. The nursing work environment is a complex construct, and its definition remains inconclusive. None of the instruments available is considered as the gold standard. EVALUATION: A comprehensive searching was undertaken in August 2021 in six databases according to PRISMA. The COSMIN and modified GRADE were applied to assess the methodological quality and measurement properties of the instruments. Instruments were categorized into three levels. The definition and construct of nursing work environment were revisited. KEY ISSUES: Forty-one studies (19 instruments) were included. One, fourteen, and four instruments are respectively appraised as A-, B- and C-level recommendation. Definition and eight labels of nursing work environment are identified. CONCLUSION: This paper provides recommendations for selecting a proper instrument for the nursing work environment. IMPLICATIONS FOR NURSING MANAGEMENT: This study helps nurse managers to select instruments and understand the construct of the nursing work environment. The eight labels can be used as a reference for tailoring policy aimed at creating a favourable nursing work environment.

Augmenting the effect of virtual labs with "teacher demonstration" and "student critique" instructional designs to scaffold the development of scientific literacy.

Virtual labs provide space for students to iteratively test, observe, and revise their understanding so as to improve their scientific literacy. However, one of the challenges that students face is that they need to think and act like scientists so as to be sensitively alert to methodological flaws and various sources of error. This study thus compared the effect of two instructional approaches using a virtual lab to enhance students' scientific literacy. Before students were given the opportunity to conduct science inquiries with the virtual lab, they were required to critique problematic inquiry cases (the critique group) or watch teachers' demonstrations (the teacher demonstration group) before taking part in the inquiry. By analyzing data from 50 middle school students, this study found that the effect of applying virtual labs can be augmented by an instructional design that engages students in critiquing experiments prior to their inquiry with the virtual lab. This study also found a limitation of the use of virtual labs in helping students transfer what they have learned from the teacher's demonstration to new inquiry contexts. A close relation among scientific literacy post-test scores, critiquing performance, and inquiry performance in the inquiry activity was detected, suggesting that student critiquing prior to inquiry is in alignment with the goal of developing students' inquiry skills and scientific literacy with virtual labs.

Clinicopathological and molecular characterisation of papillary renal neoplasm with reverse polarity and its renal papillary adenoma analogue.

AIMS: Papillary renal neoplasm with reverse polarity (PRNRP) is a newly defined entity with distinct histomorphology and recurrent KRAS mutation. It has been estimated to constitute 4% of previously diagnosed papillary renal cell carcinoma (PRCC). Renal papillary adenoma (PA) is suggested to be the precursor of PRCC. This study aimed to investigate the association between PRNRP and PA, particularly the morphologically similar type D PA. METHODS AND RESULTS: Nephrectomy specimens of PRCC and PA from our 10-year pathology archives were retrieved and reviewed. GATA3 immunohistochemistry and RAS/BRAF testing were performed in all cases reclassified as PRNRP and all PAs with sufficient materials. Overall, PRNRP accounted for 9.1% (10 of 110) of PRCC and there was no recurrence/metastasis with a mean follow-up period of 39 months. Three novel morphological features were described, including clear cell change, mast cell infiltration and metaplastic ossification. Nine of the 10 PRNRPs showed diffuse and strong GATA3 expression and KRAS missense mutations at codon 12. One case exhibited moderate GATA3 staining on 80% of the tumour cells and RAS/BRAF wild-type. In a total of 73 PAs, 11 were classified as type D. GATA3 expression was significantly more frequent in type D versus non-type D PAs (100 versus 35%, P < 0.01). KRAS missense mutations were identified in six of eight (75%) of the type D PAs but none of the 18 non-type D PAs. CONCLUSIONS: Type D PA was different from other types of PA and represented an analogue or a small-sized PRNRP for their identical morphology, immunophenotype and molecular signature.

The impacts of maternal childhood adversity, stress, and mental health on child development at 6 months in Taiwan: A follow-up study.

Exposure to adverse childhood experiences (ACEs) is not only associated with one's adverse health outcomes in adulthood but also increases the risk of child developmental problems in offspring. However, the mechanisms involved in the transmission of the effects of maternal ACEs to the offspring largely remain unexplored. This study sought to identify possible psychosocial pathways of intergenerational effects of maternal ACEs on child development at 6 months. Data from a longitudinal study on maternal childhood adversity and maternal psychosocial risk during pregnancy as well as maternal mental health problems and child development at 6 months postnatal were used. Structural equation modeling with bootstrapping was used to estimate the indirect effects of maternal ACEs on child development at 6 months. The model showed that maternal ACEs indirectly influenced offspring's development via maternal stressful events during pregnancy and pre- and postnatal mental health problems. This finding highlights the possible interventions at the prenatal and postnatal periods. Early identification of women who have ACEs or who are at psychosocial risk during pre- and postnatal periods is critical to provide interventions to buffer those negative effects on offspring's development. Future studies are needed to longitudinally assess the effects of maternal ACEs on child development over time.

Incidence and characteristics of paediatric abusive head trauma in Taiwan, 2006-2015: a nationwide population-based study.

OBJECTIVES: To examine the incidence rate and characteristics of paediatric abusive head trauma (PAHT) among children under age 5 years in Taiwan. METHODS: The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) was used to identify broad and narrow definitions of children aged under 5 years with PAHT from 2006 to 2015 in Taiwan using a representative national insurance research database. Medical resource utilisation was also analysed. Incidence rates per 100 000 person-years were calculated and presented with 95% CI. Joinpoint regression analysis was used to detect the changes in trends and calculate the annual percentage change in PAHT incidence over time. RESULTS: From 2006 to 2015, 479 (narrow definition) and 538 (broad definition) PAHT cases were identified. Incidence rates of PAHT by narrow and broad definitions among children under 1 year of age (18.7/100 000 and 20.0/100 000) were nearly 10-fold or 20-fold higher than for children aged 1-2 (1.7/100 000 and 2.1/100 000) and 3-5 (0.9/100 000 and 1.2/100 000) years. The PAHT incidence significantly increased since 2012, with trends varying by age and gender. Our results suggest that over 40% of the children with PAHT experienced serious injury and nearly 13% were fatal cases. For 87% (n=57) of fatal cases, this was their first ever hospitalisation. The number of fatal cases among infants was fourfold higher than that of children aged 1-5 years. CONCLUSIONS: This study provides a robust national estimate of PAHT and identifies infants as the most vulnerable group for PAHT in Taiwan. Education to enhance healthcare profession's sensitivity and competence for the early identification and diagnosis of PAHT is critical.

Protective Effects of Fucoxanthin on Hydrogen Peroxide-Induced Calcification of Heart Valve Interstitial Cells.

Cardiovascular diseases such as atherosclerosis and aortic valve sclerosis involve inflammatory reactions triggered by various stimuli, causing increased oxidative stress. This increased oxidative stress causes damage to the heart cells, with subsequent cell apoptosis or calcification. Currently, heart valve damage or heart valve diseases are treated by drugs or surgery. Natural antioxidant products are being investigated in related research, such as fucoxanthin (Fx), which is a marine carotenoid extracted from seaweed, with strong antioxidant, anti-inflammatory, and anti-tumor properties. This study aimed to explore the protective effect of Fx on heart valves under high oxidative stress, as well as the underlying mechanism of action. Rat heart valve interstitial cells under H2O2-induced oxidative stress were treated with Fx. Fx improved cell survival and reduced oxidative stress-induced DNA damage, which was assessed by cell viability analysis and staining with propidium iodide. Alizarin Red-S analysis indicated that Fx has a protective effect against calcification. Furthermore, Western blotting revealed that Fx abrogates oxidative stress-induced apoptosis via reducing the expression of apoptosis-related proteins as well as modulate Akt/ERK-related protein expression. Notably, in vivo experiments using 26 dogs treated with 60 mg/kg of Fx in combination with medical treatment for 0.5 to 2 years showed significant recovery in their echocardiographic parameters. Collectively, these in vitro and in vivo results highlight the potential of Fx to protect heart valve cells from high oxidative stress-induced damage.

Two Ck1δ transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock.

The N6-methylation of internal adenosines (m6A) in mRNA has been quantified and localized throughout the transcriptome. However, the physiological significance of m6A in most highly methylated mRNAs is unknown. It was demonstrated previously that the circadian clock, based on transcription-translation negative feedback loops, is sensitive to the general inhibition of m6A. Here, we show that the Casein Kinase 1 Delta mRNA (Ck1δ), coding for a critical kinase in the control of circadian rhythms, cellular growth, and survival, is negatively regulated by m6A. Inhibition of Ck1δ mRNA methylation leads to increased translation of two alternatively spliced CK1δ isoforms, CK1δ1 and CK1δ2, uncharacterized until now. The expression ratio between these isoforms is tissue-specific, CK1δ1 and CK1δ2 have different kinase activities, and they cooperate in the phosphorylation of the circadian clock protein PER2. While CK1δ1 accelerates the circadian clock by promoting the decay of PER2 proteins, CK1δ2 slows it down by stabilizing PER2 via increased phosphorylation at a key residue on PER2 protein. These observations challenge the previously established model of PER2 phosphorylation and, given the multiple functions and targets of CK1δ, the existence of two isoforms calls for a re-evaluation of past research when CK1δ1 and CK1δ2 were simply CK1δ.

Hinokitiol Exhibits Antitumor Properties through Induction of ROS-Mediated Apoptosis and p53-Driven Cell-Cycle Arrest in Endometrial Cancer Cell Lines (Ishikawa, HEC-1A, KLE).

Hinokitiol is a natural tropolone derivative that is present in the heartwood of cupressaceous plants, and has been extensively investigated for its anti-inflammatory, antioxidant, and antitumor properties in the context of various diseases. To date, the effects of hinokitiol on endometrial cancer (EC) has not been explored. The purpose of our study was to investigate the anti-proliferative effects of hinokitiol on EC cells. Cell viability was determined with an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and the quantification of apoptosis and reactive oxygen species (ROSs) was performed by using flow cytometry, while protein expression was measured with the Western blotting technique. Hinokitiol significantly suppressed cell proliferation through the inhibition of the expression of cell-cycle mediators, such as cyclin D1 and cyclin-dependent kinase 4 (CDK4), as well as the induction of the tumor suppressor protein p53. In addition, hinokitiol increased the number of apoptotic cells and increased the protein expression of cleaved-poly-ADP-ribose polymerase (PARP) and active cleaved-caspase-3, as well as the ratio of Bcl-2-associated X protein (Bax) to B-cell lymphoma 2 (Bcl-2). Interestingly, except for KLE cells, hinokitiol induced autophagy by promoting the accumulation of the microtubule-associated protein light chain 3B (LC3B) and reducing the sequestosome-1 (p62/SQSTM1) protein level. Furthermore, hinokitiol triggered ROS production and upregulated the phosphorylation of extracellular-signal-regulated kinase (p-ERK1/2) in EC cells. These results demonstrate that hinokitiol has potential anti-proliferative and pro-apoptotic benefits in the treatment of endometrial cancer cell lines (Ishikawa, HEC-1A, and KLE).

Betulinic Acid Affects the Energy-Related Proteomic Profiling in Pancreatic Ductal Adenocarcinoma Cells.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a 5-year survival rate of <8%. Therefore, finding new treatment strategies against PDAC cells is an imperative issue. Betulinic acid (BA), a plant-derived natural compound, has shown great potential to combat cancer owing to its versatile physiological functions. In this study, we observed the impacts of BA on the cell viability and migratory ability of PDAC cell lines, and screened differentially expressed proteins (DEPs) by an LC-MS/MS-based proteomics analysis. Our results showed that BA significantly inhibited the viability and migratory ability of PDAC cells under a relatively low dosage without affecting normal pancreatic cells. Moreover, a functional analysis revealed that BA-induced downregulation of protein clusters that participate in mitochondrial complex 1 activity and oxidative phosphorylation, which was related to decreased expressions of RNA polymerase mitochondrial (POLRMT) and translational activator of cytochrome c oxidase (TACO1), suggesting that the influence on mitochondrial function explains the effect of BA on PDAC cell growth and migration. In addition, BA also dramatically increased Apolipoprotein A1 (APOA1) expression and decreased NLR family CARD domain-containing protein 4 (NLRC4) expression, which may be involved in the dampening of PDAC migration. Notably, altered expression patterns of APOA1 and NLRC4 indicated a favorable clinical prognosis of PDAC. Based on these findings, we identified potential proteins and pathways regulated by BA from a proteomics perspective, which provides a therapeutic window for PDAC.

[Implementation of Trauma-Informed Healthcare].

Trauma that is rooted in extremely stressful events is an important factor affecting human health. Patients who have experienced trauma may present in a variety of different ways in healthcare settings. One of these ways is the exhibiting of strong emotional or behavioral reactions triggered by traumatic memories. Caring for patients affected by known or unknown trauma is a significant challenge for healthcare providers. The core of trauma-informed care includes understanding trauma; respecting, empathizing and responding to the needs and reactions of patients with trauma; and providing care in a manner that prevents re-traumatization. In this article, the impact of trauma on overall health is introduced followed by a presentation of trauma triggers in the healthcare context, underscoring the importance of prioritizing care for patients with a history of trauma. Lastly, the concept and principles of trauma-informed care are incorporated into healthcare practice, providing specific, practical application strategies for healthcare providers to use in clinical settings. Trauma-informed healthcare practice relies on healthcare providers and organizations working together. The principles include the self-awareness and self-care of healthcare providers, awareness of the patient's trauma reaction, ensuring patient safety, building trust and transparency in care, working collaboratively with the patient and the healthcare team, and providing choices and empowerment during the care process. This article provides a reference to healthcare providers for providing friendly and high-quality care to patients with trauma.

Examining secondary school students' views of model evaluation through an integrated framework of personal epistemology.

The aim of the study was to investigate students' views of model evaluation through the lens of personal epistemology. We developed an integrated analytical framework by combining a developmental framework, including absolutist, multiplist, and evaluatist, with a multi-dimensional framework, including limits of knowing, certainty of knowing, and criteria of knowing. Furthermore, we examined the potential influence of the question contexts and the students' grade levels. A total of 188 secondary school students were surveyed. Students answered two sets of model evaluation questions based on two scientific contexts. After reading the information about the two models, the students had to choose from three epistemic assumptions and then provide written justifications explaining their choice of assumptions. Quantitative and qualitative analyses were conducted for the multiple-choice questions and the written responses. In both contexts there were higher percentages of 11th-grade students choosing the evaluatist assumptions than the eighth-grade students. For students choosing multiplist and evaluatist assumptions, the 11th-grade students were more likely than the eighth-grade students to think in terms of pragmatic and evidential criteria as the criteria of knowing. Different contexts of the questions evoked different views of model evaluation particularly regarding the limits of knowing. Four additional categories of epistemic levels also emerged from the data. This study provides a new framework for understanding students' thinking about model evaluation. Implications and suggestions for future research are provided.

Identification of the Effects of Aspirin and Sulindac Sulfide on the Inhibition of HMGA2-Mediated Oncogenic Capacities in Colorectal Cancer.

Distant metastatic colorectal cancer (CRC) is present in approximately 25% of patients at initial diagnosis, and eventually half of CRC patients will develop metastatic disease. The 5-year survival rate for patients with metastatic CRC is a mere 12.5%; thus, there is an urgent need to investigate the molecular mechanisms of cancer progression in CRC. High expression of human high-mobility group A2 (HMGA2) is related to tumor progression, a poor prognosis, and a poor response to therapy for CRC. Therefore, HMGA2 is an attractive target for cancer therapy. In this study, we identified aspirin and sulindac sulfide as novel potential inhibitors of HMGA2 using a genome-wide mRNA signature-based approach. In addition, aspirin and sulindac sulfide induced cytotoxicity of CRC cells stably expressing HMGA2 by inhibiting cell proliferation and migration. Moreover, a gene set enrichment analysis (GSEA) revealed that gene sets related to inflammation were positively correlated with HMGA2 and that the main molecular function of these genes was categorized as a G-protein-coupled receptor (GPCR) activity event. Collectively, this is the first study to report that aspirin and sulindac sulfide are novel potential inhibitors of HMGA2, which can induce cytotoxicity of CRC cells stably expressing HMGA2 by inhibiting cell proliferation and migration through influencing inflammatory-response genes, the majority of which are involved in GPCR signaling.