Evaluation of Pm2.5 Influence on Human Lung Cancer Cells Using a Microfluidic Platform.

In this study, we developed a microfluidic device that is able to monitor cell biology under continuous PM2.5 treatment. The effects of PM2.5 on human alveolar basal epithelial cells, A549 cells, and uncovered several significant findings were investigated. The results showed that PM2.5 exposure did not lead to a notable decrease in cell viability, indicating that PM2.5 did not cause cellular injury or death. However, the study found that PM2.5 exposure increased the invasion and migration abilities of A549 cells, suggesting that PM2.5 might promote cell invasiveness. Results of RNA sequencing revealed 423 genes that displayed significant differential expression in response to PM2.5 exposure, with a particular focus on pathways associated with the generation of reactive oxygen species (ROS) and mitochondrial dysfunction. Real-time detection demonstrated an increase in ROS production in A549 cells after exposure to PM2.5. JC1 assay, which indicated a loss of mitochondrial membrane potential (ΔΨm) in A549 cells exposed to PM2.5. The disruption of mitochondrial membrane potential further supports the detrimental effects of PM2.5 on A549 cells. These findings highlight several adverse effects of PM2.5 on A549 cells, including enhanced invasion and migration capabilities, altered gene expression related to ROS pathways, increased ROS production and disruption of mitochondrial membrane potential. These findings contribute to our understanding of the potential mechanisms through which PM2.5 can impact cellular function and health.

Mapping scoping reviews in neurosurgery: a scoping review protocol.

INTRODUCTION: The realm of neurosurgery is currently witnessing a surge in primary research, underscoring the importance of adopting evidence-based approaches. Scoping reviews, as a type of evidence synthesis, offer a broad perspective and have become increasingly vital for managing the ever-expanding body of research in swiftly evolving fields. Recent research has indicated a rising prevalence of scoping reviews in healthcare literature. In this context, the concept of a 'review of scoping reviews' has emerged as a means to offer a higher level synthesis of insights. However, the field of neurosurgery appears to lack a comprehensive integration of scoping reviews. Therefore, the objective of this scoping review is to identify and evaluate the extent of scoping reviews within neurosurgery, pinpointing research gaps and methodological issues to enhance evidence-based practices in this dynamic discipline. METHODS: The method framework of Arksey and O'Malley will be used to conduct the scoping review. A thorough literature search will be performed on Medline, Scopus and Web of Science to find eligible studies using the keywords related to neurosurgery, scoping review and its variants. Two reviewers will independently revise all of the full-text articles, extract data and evaluate the study extent. A narrative overview of the findings from included studies will be given. ETHICS AND DISSEMINATION: This review will involve secondary analysis of published literature, and therefore ethics approval is not required. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist will be used to guide translation of findings. Results will be disseminated through peer-reviewed journals and presented in conferences via abstract and presentation.

Cytotoxicity and Multi-Enzyme Inhibition of Nepenthes miranda Stem Extract on H838 Human Non-Small Cell Lung Cancer Cells and RPA32, Elastase, Tyrosinase, and Hyaluronidase Proteins.

The carnivorous pitcher plants of the genus Nepenthes have long been known for their ethnobotanical applications. In this study, we prepared various extracts from the pitcher, stem, and leaf of Nepenthes miranda using 100% ethanol and assessed their inhibitory effects on key enzymes related to skin aging, including elastase, tyrosinase, and hyaluronidase. The cytotoxicity of the stem extract of N. miranda on H838 human lung carcinoma cells were also characterized by effects on cell survival, migration, proliferation, apoptosis induction, and DNA damage. The cytotoxic efficacy of the extract was enhanced when combined with the chemotherapeutic agent 5-fluorouracil (5-FU), indicating a synergistic effect. Flow cytometry analysis suggested that the stem extract might suppress H838 cell proliferation by inducing G2 cell cycle arrest, thereby inhibiting carcinoma cell proliferation. Gas chromatography-mass spectrometry (GC-MS) enabled the tentative identification of the 15 most abundant compounds in the stem extract of N. miranda. Notably, the extract showed a potent inhibition of the human RPA32 protein (huRPA32), critical for DNA replication, suggesting a novel mechanism for its anticancer action. Molecular docking studies further substantiated the interaction between the extract and huRPA32, highlighting bioactive compounds, especially the two most abundant constituents, stigmast-5-en-3-ol and plumbagin, as potential inhibitors of huRPA32's DNA-binding activity, offering promising avenues for cancer therapy. Overall, our findings position the stem extract of N. miranda as a promising source of natural compounds for anticancer therapeutics and anti-skin-aging treatments, warranting further investigation into its molecular mechanisms and potential clinical applications.

Collaborative clinical reasoning: a scoping review.

Background: Collaborative clinical reasoning (CCR) among healthcare professionals is crucial for maximizing clinical outcomes and patient safety. This scoping review explores CCR to address the gap in understanding its definition, structure, and implications. Methods: A scoping review was undertaken to examine CCR related studies in healthcare. Medline, PsychInfo, SciVerse Scopus, and Web of Science were searched. Inclusion criteria included full-text articles published between 2011 to 2020. Search terms included cooperative, collaborative, shared, team, collective, reasoning, problem solving, decision making, combined with clinical or medicine or medical, but excluded shared decision making. Results: A total of 24 articles were identified in the review. The review reveals a growing interest in CCR, with 14 articles emphasizing the decision-making process, five using Multidisciplinary Team-Metric for the Observation of Decision Making (MDTs-MODe), three exploring CCR theory, and two focusing on the problem-solving process. Communication, trust, and team dynamics emerge as key influencers in healthcare decision-making. Notably, only two articles provide specific CCR definitions. Conclusions: While decision-making processes dominate CCR studies, a notable gap exists in defining and structuring CCR. Explicit theoretical frameworks, such as those proposed by Blondon et al. and Kiesewetter et al., are crucial for advancing research and understanding CCR dynamics within collaborative teams. This scoping review provides a comprehensive overview of CCR research, revealing a growing interest and diversity in the field. The review emphasizes the need for explicit theoretical frameworks, citing Blondon et al. and Kiesewetter et al. The broader landscape of interprofessional collaboration and clinical reasoning requires exploration.

Correction: Influence of alcohol provocation on medical professionals in Taiwan: A qualitative study.

[This corrects the article DOI: 10.1371/journal.pone.0264071.].

An Investigation of Patient Preferences and Gender Dynamics of Neurosurgeon Selection in Taiwan: A Mixed-Method Study.

OBJECTIVE: To investigate the influence of gender on patient preferences during the selection of neurosurgeons. METHODS: A mixed-method, cross-sectional study was conducted at Linkou Chang Gung Memorial Hospital in Taiwan, involving 60 patients. The study encompassed both structured questionnaires and in-depth interviews, administered postpatient-surgeon interactions to assess the nuanced effect of surgeon gender on patient choice. A balanced representation of both genders was ensured among the neurosurgeons involved. Thematic analysis was employed for textual data, while numeric data were analyzed using descriptive and Chi-square statistics. RESULTS: The majority of participants (n = 40, 66.7%) expressed no preference regarding the gender of their neurosurgeon during outpatient consultations. Nonetheless, a notable fraction, predominantly female, preferred female neurosurgeons (n = 20, 33.3%). Statistical analysis highlighted a significant correlation between the gender of the patients and their preferred neurosurgeon's gender, with female patients predominantly favouring female neurosurgeons (P < 0.05). Qualitative insights indicate that, although professional skill and experience are primary factors in selecting a neurosurgeon, a latent gender preference exists, influenced by perceived privacy, empathetic care, and the surgical finesse associated with female neurosurgeons. CONCLUSIONS: Although expertise and professionalism are of paramount importance, there is a clear preference for female neurosurgeons, especially among female patients. These findings underscore the importance of recognizing and accommodating patients' preferences to ensure neurosurgical care aligns with patient comfort, expectations, and the broader movement towards gender equality.

Factors Contributing to Non-Concordance Between End-of-Life Care and Advance Care Planning.

CONTEXT: Despite making do-not-resuscitate or comfort care decisions during advance care planning, terminally ill patients sometimes receive life-sustaining treatments as they approach end of life. OBJECTIVES: To examine factors contributing to nonconcordance between end-of-life care and advance care planning. METHODS: In this longitudinal retrospective cohort study, terminally ill patients with a life expectancy shorter than six months, who had previously expressed a preference for do-not-resuscitate or comfort care, were followed up after palliative shared care intervention. An instrument with eight items contributing to non-concordant care, developed through literature review and experts' consensus, was employed. An expert panel reviewed electronic medical records to determine factors associated with non-concordant care for each patient. Statistical analysis, including descriptive statistics and the chi-square test, examines demographic characteristics, and associations. RESULTS: Among the enrolled 7871 patients, 97 (1.2%) received non-concordant care. The most prevalent factor was "families being too distressed about the patient's deteriorating condition and therefore being unable to let go" (84.5%) followed by "limited understanding of medical interventions among patients and surrogates" (38.1%), and "lack of patient participation in the decision-making process" (25.8%). CONCLUSIONS: This study reveals that factors related to relational autonomy, emotional support, and health literacy may contribute to non-concordance between advance care planning and end-of-life care. In the future, developing an advance care planning model emphasizes respecting relational autonomy, providing emotional support, and enhancing health literacy could help patients receiving a goal concordant and holistic end-of-life care.

P-Selectin mediates targeting of a self-assembling phototherapeutic nanovehicle enclosing dipyridamole for managing thromboses.

Thrombotic vascular disorders, specifically thromboembolisms, have a significant detrimental effect on public health. Despite the numerous thrombolytic and antithrombotic drugs available, their efficacy in penetrating thrombus formations is limited, and they carry a high risk of promoting bleeding. Consequently, the current medication dosage protocols are inadequate for preventing thrombus formation, and higher doses are necessary to achieve sufficient prevention. By integrating phototherapy with antithrombotic therapy, this study addresses difficulties related to thrombus-targeted drug delivery. We developed self-assembling nanoparticles (NPs) through the optimization of a co-assembly engineering process. These NPs, called DIP-FU-PPy NPs, consist of polypyrrole (PPy), dipyridamole (DIP), and P-selectin-targeted fucoidan (FU) and are designed to be delivered directly to thrombi. DIP-FU-PPy NPs are proposed to offer various potentials, encompassing drug-loading capability, targeted accumulation in thrombus sites, near-infrared (NIR) photothermal-enhanced thrombus management with therapeutic efficacy, and prevention of rethrombosis. As predicted, DIP-FU-PPy NPs prevented thrombus recurrence and emitted visible fluorescence signals during thrombus clot penetration with no adverse effects. Our co-delivery nano-platform is a simple and versatile solution for NIR-phototherapeutic multimodal thrombus control.

COVID-19-related stress among emergency physicians: a scoping review protocol on the stressors and coping strategies.

OBJECTIVE: This scoping review aims to identify the COVID-19-related stressors and the corresponding coping strategies among emergency physicians during and following the pandemic. INTRODUCTION: In the midst of an unprecedented COVID-19 crisis, healthcare professionals confront a diverse set of difficulties. Emergency physicians are under immense pressure. They must provide frontline care and make quick decisions in a high-pressure environment. This can lead to a variety of physical and psychological stressors, including extended working hours, increased workload, personal risk of infection and the emotional toll of caring for infected patients. It is critical that they be informed of the numerous stressors they face, as well as the various coping methods accessible to them, in order to deal with these pressures. INCLUSION CRITERIA: This paper will summarise the findings of primary or secondary investigations on emergency physicians' stressors and coping strategies during and following the COVID-19 epidemic. All journals and grey literature in English and Mandarin published after January 2020 are eligible. METHODS: The Joanna Briggs Institute (JBI) method will be used to conduct the scoping review. A thorough literature search will be performed on OVID Medline, Scopus and Web of Science to find eligible studies, using the keywords related to emergency physicians, stress and coping strategies. Two reviewers will independently revise all of the full-text articles, extract data and evaluate the study quality. A narrative overview of the findings from included studies will be given. ETHICS AND DISSEMINATION: This review will involve secondary analysis of published literature, and therefore ethics approval is not required. The Preferred Reporting Items for Systematic reviews and Meta-Analyses checklist will be used to guide translation of findings. Results will be disseminated through peer-reviewed journals and presented in conferences via abstract and presentation.

Long-term Outcome of Seizure Control and Neurologic Performance After Limited Hippocampal Radiofrequency Thermocoagulation for Mesial Temporal Lobe Epilepsy.

OBJECTIVE: Limited hippocampal radiofrequency thermocoagulation (RFTC) for patients with mesial temporal lobe epilepsy was associated with good short-term seizure control and few complications. We aimed to demonstrate the neuropsychologic outcomes and assess the prognostic factors of long-term seizure control in these patients. METHODS: We included all patients with mesial temporal lobe epilepsy who underwent limited hippocampal RFTC from January 2016 to December 2020. Clinical data of age, sex, seizure control before and after operation were all corrected. Pre- and postoperative neuropsychologic function including full-scale intelligence quotient (FSIQ), memory quotient, and the Mini-Mental State Examination was used. RESULTS: Thirty-one patients (17 female and 14 male) with a mean epilepsy duration of 22.3 years and seizure frequency of 5.7 times per month were included. The intraoperative seizure rate was 19.3%, and a higher preoperative seizure frequency (P = 0.001) and longer duration of epilepsy (P = 0.042) were associated with the occurrence of intraoperative seizures. The postoperative FSIQ scores were significantly better than preoperative scores (mean 92.1 vs. 89.7, P = 0.014). Nine patients (29%) who underwent limited hippocampal RFTC were seizure-free at 1 year of follow-up. Responders represented 58% (n = 18) of patients at 1 year. The mean follow-up period was 34.7 ± 13.3 months. Five patients remained seizure free and 13 patients are still responders at the last follow-up visits. Long-term seizure frequency was 2.32 ± 2.86 times per month. CONCLUSIONS: Limited hippocampal RFTC is a safe stereotactic minimal invasive procedure with good neuropsychologic outcome and acceptable efficacy of seizure reduction in appropriately selected patients.

Medical Dispute Cases Caused by Errors in Clinical Reasoning: An Investigation and Analysis.

Studies that examine medical dispute cases (MDC) due to clinical reasoning (CR) are scarce in Taiwan. A retrospective analysis was undertaken to review MDC filed at four hospitals in Taiwan between 2011 and 2015. Cases were examined for the healthcare professionals involved, their relevance to CR errors, clinical specialties, and seniority. Seventy-eight MDC were identified and 57.7% of which were determined to be related to CR errors (n = 45). Among the 45 cases associated with CR errors, 82.2% (37) and 22.2% (10) were knowledge- and skill-related errors, respectively. The healthcare professionals with the most MDC were obstetrician-gynecologists (10/90, 11.1%), surgeons (8/90, 8.9%), and emergency physicians (7/90, 7.8%). The seniority of less than 5 years or lower had the highest number of attending physicians to be associated with MDC. In contrast, the highest seniority (>25 years) in the physician group and year 6 in the resident group are both shown with zero MDC. In our study, the larger hospitals had a significantly higher incidence of MDC compared to the smaller hospitals (Pearson Correlation Coefficient = 0.984, p = 0.016). An examination of MDC reveals the frequency and nature of medical errors in Taiwanese hospitals. Having identified that CR errors contributed a substantial fraction to the overall MDC, strategies to promote reasoning skills and hence reduce medico-legal issues help safeguard both patients and healthcare professionals.

Usability of deep learning and H&E images predict disease outcome-emerging tool to optimize clinical trials.

Understanding factors that impact prognosis for cancer patients have high clinical relevance for treatment decisions and monitoring of the disease outcome. Advances in artificial intelligence (AI) and digital pathology offer an exciting opportunity to capitalize on the use of whole slide images (WSIs) of hematoxylin and eosin (H&E) stained tumor tissue for objective prognosis and prediction of response to targeted therapies. AI models often require hand-delineated annotations for effective training which may not be readily available for larger data sets. In this study, we investigated whether AI models can be trained without region-level annotations and solely on patient-level survival data. We present a weakly supervised survival convolutional neural network (WSS-CNN) approach equipped with a visual attention mechanism for predicting overall survival. The inclusion of visual attention provides insights into regions of the tumor microenvironment with the pathological interpretation which may improve our understanding of the disease pathomechanism. We performed this analysis on two independent, multi-center patient data sets of lung (which is publicly available data) and bladder urothelial carcinoma. We perform univariable and multivariable analysis and show that WSS-CNN features are prognostic of overall survival in both tumor indications. The presented results highlight the significance of computational pathology algorithms for predicting prognosis using H&E stained images alone and underpin the use of computational methods to improve the efficiency of clinical trial studies.

Leptin Silencing Attenuates Lipid Accumulation through Sterol Regulatory Element-Binding Protein 1 Inhibition in Nasopharyngeal Carcinoma.

Leptin is a crucial regulator of metabolism and energy homeostasis in mammals. Many studies have investigated the impacts of leptin on human cancers, such as proliferation and metastasis. However, the mechanisms underlying leptin-mediated regulation of lipid metabolism in nasopharyngeal carcinoma (NPC) remain incompletely understood. In the current study, leptin downregulation ameliorated lipid accumulation, triglyceride, and cholesterol levels. Mechanistically, diminished leptin by siRNA not only inhibited sterol regulatory element-binding protein 1 (SREBP1), a master regulator of lipid metabolism, at the mRNA and protein levels, but also reduced SREBP1 downstream target expressions, such as fatty acid synthase (FASN) and stearoyl-CoA desaturase-1 (SCD1), in NPC cells. In addition, leptin expression could modulate the promoter activity of SREBP1. We also found that pharmacological inhibition of poly-ADP ribose polymerase-γ (PPAR-γ) resulted in increased SREBP1 expression in leptin-depleted NPC cells. Functionally, SREBP1 overexpression overcame the effects of leptin-silencing attenuated triglyceride level, cholesterol level and cell survival in NPC cells. Taken together, our results demonstrate that leptin is an important regulator of lipid metabolism in NPC cells and might could be a potential therapeutic target for treatment of NPC patients.

Influence of alcohol provocation on medical professionals in Taiwan: A qualitative study.

There is a paucity of research on the issue of alcohol provocation in the medical field. While studies have been performed concerning alcohol abuse among students, no studies have concentrated on alcohol provocation among medical professionals. Therefore, it is essential to look at the underlying factors that may influence alcohol use by medical professionals. A qualitative study using focus groups was conducted to construct themes depicting medical professionals' experiences of alcohol provocation. Physicians (n = 32) and residents (n = 29) were recruited from a large teaching hospital in Taiwan. The volunteers included both subjects and instigators of alcohol provocation (individuals being pressured to drink and those who exert such pressure on others). A questionnaire on their alcohol use was used to quantitatively assess the prevalence of alcohol consumption and inebriation. The participants were then interviewed separately in groups. All interview data were recorded, transcribed and analysed thematically. A notable prevalence of recent alcohol consumption was observed in both the physicians (n = 18, 56%) and residents (n = 17, 59%). Three prominent themes were identified and summarized: (1) Social drinking in the Taiwanese medical profession (2) Workplace hierarchy and changes in drinking culture, and (3) Influence on the medical profession. The behaviour of alcohol provocation among these medical professionals was revealed with its underlying factors of specific cultural norms, workplace hierarchy and social expectations. An understanding of alcohol provocation helps increase the awareness of adverse consequences associated with alcohol provocation, encourage medical professionals to avoid inappropriate drinking behaviors, and reduce the risk of compromising medical professionalism.

Glomerular disease classification and lesion identification by machine learning.

BACKGROUND: Classification of glomerular diseases and identification of glomerular lesions require careful morphological examination by experienced nephropathologists, which is labor-intensive, time-consuming, and prone to interobserver variability. In this regard, recent advance in machine learning-based image analysis is promising. METHODS: We combined Mask Region-based Convolutional Neural Networks (Mask R-CNN) with an additional classification step to build a glomerulus detection model using human kidney biopsy samples. A Long Short-Term Memory (LSTM) recurrent neural network was applied for glomerular disease classification, and another two-stage model using ResNeXt-101 was constructed for glomerular lesion identification in cases of lupus nephritis. RESULTS: The detection model showed state-of-the-art performance on variedly stained slides with F1 scores up to 0.944. The disease classification model showed good accuracies up to 0.940 on recognizing different glomerular diseases based on H&E whole slide images. The lesion identification model demonstrated high discriminating power with area under the receiver operating characteristic curve up to 0.947 for various glomerular lesions. Models showed good generalization on external testing datasets. CONCLUSION: This study is the first-of-its-kind showing how each step of kidney biopsy interpretation carried out by nephropathologists can be captured and simulated by machine learning models. The models were integrated into a whole slide image viewing and annotating platform to enable nephropathologists to review, correct, and confirm the inference results. Further improvement on model performances and incorporating inputs from immunofluorescence, electron microscopy, and clinical data might realize actual clinical use.

Safety, Feasibility, and Effects of Short-Term Calorie Reduction during Induction Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma: A Pilot Study.

Short-term calorie reduction (SCR) requires individuals to reduce their calorie intake to less than 50% of normal requirements and has shown good tolerance and potential benefits in prior studies addressing gynecological cancer patients. More studies are needed to further confirm its safety, feasibility, and effects in patients with different cancers, including hematological malignancies. This pilot cohort study with a matched-pair comparison group was registered at ClinicalTrails.gov [201810112RIND]. Adult patients diagnosed with advanced-stage diffuse large-B cell lymphoma were recruited (SCR group) and matched with one comparison patient (comparison group), each in a manner blinded to their outcomes. The SCR group undertook at least two cycles of 48 h water fast along with their chemotherapy R-CHOP. Descriptive analysis and generalized estimating equations were used to analyze the data. Six participants completed multiple cycles of SCR and were compared to their six counterparts in the comparison group. The results showed that SCR is safe and feasible in terms of a high compliance rate and stable nutritional status. The SCR was associated with benefits in post-chemotherapy hematological parameters (i.e., erythrocyte [p < 0.001] and lymphocyte counts [p < 0.001]). More randomized controlled trials are needed to validate the effects of SCR on different types of cancer populations.

A scoping review of clinical reasoning research with Asian healthcare professionals.

Clinical reasoning is the thought process that guides practice. Although a plethora of clinical reasoning studies in healthcare professionals exists, the majority appear to originate from Western cultures. A scoping review was undertaken to examine clinical reasoning related research across Asian cultures. PubMed, SciVerse Scopus, Web of Science and Airiti Library databases were searched. Inclusion criteria included full-text articles published in Asian countries (2007 to 2019). Search terms included clinical reasoning, thinking process, differential diagnosis, decision making, problem-based learning, critical thinking, healthcare profession, institution, medical students and nursing students. After applying exclusion criteria, n = 240 were included in the review. The number of publications increased in 2012 (from 5%, n = 13 in 2011 to 9%, n = 22) with a steady increase onwards to 12% (n = 29) in 2016. South Korea published the most articles (19%, n = 46) followed by Iran (17%, n = 41). Nurse Education Today published 11% of the articles (n = 26), followed by BMC Medical Education (5%, n = 13). Nursing and Medical students account for the largest population groups studied. Analysis of the articles resulted in seven themes: Evaluation of existing courses (30%, n = 73) being the most frequently identified theme. Only seven comparative articles showed cultural implications, but none provided direct evidence of the impact of culture on clinical reasoning. We illuminate the potential necessity of further research in clinical reasoning, specifically with a focus on how clinical reasoning is affected by national culture. A better understanding of current clinical reasoning research in Asian cultures may assist curricula developers in establishing a culturally appropriate learning environment.