Evaluating the risk of malignancies of the diagnostic categories proposed by the World Health Organization System for Reporting Lung Cytopathology: a two-year single institutional experience.

Introduction The WHO System of Reporting Lung Cytopathology proposed a 5-tiered system in 2023. We report the risk of malignancies (ROMs) of bronchial washing/lavage and percutaneous fine needle aspiration (FNA) specimens. We also evaluated the change of ROMs when image correlation is required. Methods Lung cytology cases in 2021 and 2022 with histologic follow-up were included. CT reports were reviewed to identify cases with a solid nodule/tumor but benign cytological findings. These were reassigned from the "Benign" to "Non-diagnostic" category, and the ROMs were re-estimated. Results A total of 1031 bronchial washing/lavage and 206 FNAs were identified. The ROMs of bronchial washing/lavage were "Non-diagnostic" 56.5% (13/23), "Benign" 41.9% (320/764), "Atypical" 71.7% (71/99), "Suspicious for malignancy" 94.7% (72/76), and "Malignant" 100% (70/70). The ROMs of FNAs were "Non-diagnostic" 66% (33/50), "Benign" 58.2% (39/67), "Atypical" 70% (28/40), "Suspicious for malignancy" 96.2% (25/26), and "Malignant" 100% (70/70). When image finding was considered, cases initially assigned as "Benign" were re-classified to "Non-diagnostic" with decreases in ROMs for the "Benign " category. Conclusions Malignancy risks associated with the WHO System of Reporting Lung Cytopathology diagnostic groups were reported. Image correlation for the "Benign" category led to a decrease in case number and ROM.

Risk factors and early detection of joint damage in patients with psoriasis: a case-control study.

BACKGROUND: Our aim was to target the unsatisfied need for early detection of the at-risk population and determine the subgroup of patients whose psoriasis (PsO) could transform into psoriatic arthritis (PsA). METHODS: A retrospective and longitudinal case-control study was conducted at Beijing Chao-yang Hospital. It included 75 patients who were clinically diagnosed with PsA in the case group and 345 who solely suffered from PsO without PsA in the control group. A variety of baseline covariates were gathered from every patient with PsO. Univariate and multivariate analyses and receiver operating characteristic (ROC) curves were used to identify underlying risk factors and determine whether it was necessary to examine the imaging of PsO patients. RESULTS: In multivariate logistic regression analysis, age ≥40 (odds ratio (OR): 1.04, 95% confidence interval (CI): 1.02-1.06, P < 0.01), nail involvement (OR: 1.17, 95% CI: 1.09-1.32, P < 0.01), erythrocyte sedimentation rate (ESR) (OR: 1.03, 95% CI: 1.01-1.06, P < 0.05) and elevated high-sensitivity C-reactive protein (hs-CRP) (OR: 1.31, 95% CI: 1.13-1.53, P < 0.01) were perceived to be risk factors for the transformation from PsO into clinical PsA. By combining magnetic resonance imaging (MRI)-detected enthesitis with tenosynovitis, combined predictors demonstrated better diagnostic efficacy, with an improvement in specificity (94.3% vs. 69%) and similarities in sensitivity (89% vs. 84.6%). The areas under the ROC curve (AUCs) amounted to 0.925 (95% CI: 0.882-0.967, P < 0.01) and 0.858 (95% CI: 0.814-0.903, P < 0.01). CONCLUSIONS: It was identified that age ≥40, nail involvement, as well as an elevated ESR, and hs-CRP served as independent risk factors for PsO transforming into PsA. Additionally, MRI provides additional value for the early recognition of PsA.

"Maintain Professionalism": Nurses' Experiences in Caring for Patients with Malignant Fungating Wounds in Taiwan.

CONTEXT: Malignant fungating wounds (MFWs) occur among 5%-15% of patients with terminal cancers, the uncontrollable symptoms result in serious psychosocial issues, thereby reducing the quality of life. Caring for MFWs impacts caregivers, including healthcare personnel. While existing studies are patient-focused, the impact of care experiences and associated support for nurses has not been examined. OBJECTIVES: To explore the experiences in caring for patients with MFWs among nurses in Taiwan. METHODS: Qualitative study with a phenomenological approach by thematic analysis was conducted with semi-structured interviews. About 15 nurses who cared for patients with MFWs at local district hospitals in Southern Taiwan. RESULTS: Four themes were identified to describe the phenomenon: (1) Fear of Unpredictability (2) Maintaining Professionalism (3) Feeling Helpless (4) Rationalizing the Negatives. The themes illustrated the distress of managing physical symptoms and highlighted how nurses strived to promote comfort for patients. Nurses felt helpless about the incurable nature of MFWs but found a way to suppress their feelings. CONCLUSION: The findings suggested the need for addressing the emotional well-being of nurses who take care of patients with MFWs. Future studies should identify effective coping strategies for nurses' health when caring for this population.

Comparison of the mesodermal differentiation potential between embryonic stem cells and scalable induced pluripotent stem cells.

BACKGROUND: Mesenchymal stem cells (MSCs) have promising potential in clinical application, whereas their limited amount and sources hinder their bioavailability. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have become prominent options in regenerative medicine as both possess the ability to differentiate into MSCs. METHODS: Recently, our research team has successfully developed human leukocyte antigen (HLA)-homozygous iPSC cell lines with high immune compatibility, covering 13.5% of the Taiwanese population. As we deepen our understanding of the differences between these ESCs and HLA-homozygous iPSCs, our study focused on morphological observations and flow cytometry analysis of specific surface marker proteins during the differentiation of ESCs and iPSCs into MSCs. RESULTS: The results showed no significant differences between the two pluripotent stem cells, and both of them demonstrated the equivalent ability to further differentiate into adipose, cartilage, and bone cells. CONCLUSION: Our research revealed that these iPSCs with high immune compatibility exhibit the same differentiation potential as ESCs, enhancing the future applicability of highly immune-compatible iPSCs.

Increased Apolipoprotein A1 Expression Correlates with Tumor-Associated Neutrophils and T Lymphocytes in Upper Tract Urothelial Carcinoma.

An increased neutrophil-to-lymphocyte ratio (NLR) is a poor prognostic biomarker in various types of cancer, because it reflects the inhibition of lymphocytes in the circulation and tumors. In urologic cancers, upper tract urothelial carcinoma (UTUC) is known for its aggressive features and lack of T cell infiltration; however, the association between neutrophils and suppressed T lymphocytes in UTUC is largely unknown. In this study, we examined the relationship between UTUC-derived factors and tumor-associated neutrophils or T lymphocytes. The culture supernatant from UTUC tumor tissue modulated neutrophils to inhibit T cell proliferation. Among the dominant factors secreted by UTUC tumor tissue, apolipoprotein A1 (Apo-A1) exhibited a positive correlation with NLR. Moreover, tumor-infiltrating neutrophils were inversely correlated with tumor-infiltrating T cells. Elevated Apo-A1 levels in UTUC were also inversely associated with the population of tumor-infiltrating T cells. Our findings indicate that elevated Apo-A1 expression in UTUC correlates with tumor-associated neutrophils and T cells. This suggests a potential immunomodulatory effect on neutrophils and T cells within the tumor microenvironment, which may represent therapeutic targets for UTUC treatment.

Dysregulation of the circRNA_0087207/miR-548c-3p/PLSR1-TGFB2 axis in Leber hereditary optic neuropathy in vitro.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is mainly the degeneration of retinal ganglion cells (RGCs) associated with high apoptosis and reactive oxygen species (ROS) levels, which is accepted to be caused by the mutations in the subunits of complex I of the mitochondrial electron transport chain. The treatment is still infant while efforts of correcting genes or using antioxidants do not bring good and consistent results. Unaffected carrier carries LHON mutation but shows normal phenotype, suggesting that the disease's pathogenesis is complex, in which secondary factors exist and cooperate with the primary complex I dysfunction. METHODS: Using LHON patient-specific induced pluripotent stem cells (iPSCs) as the in vitro disease model, we previously demonstrated that circRNA_0087207 had the most significantly higher expression level in the LHON patient-iPSC-derived RGCs compared with the unaffected carrier-iPSC-derived RGCs. To elaborate the underlying pathologies regulated by circRNA_008720 mechanistically, bioinformatics analysis was conducted and elucidated that circRNA_0087207 could act as a sponge of miR-548c-3p and modulate PLSCR1/TGFB2 levels in ND4 mutation-carrying LHON patient-iPSC-derived RGCs. RESULTS: Using LHON iPSC-derived RGCs as the disease-based platform, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on targeted mRNA of miR-548c-3p showed the connection with apoptosis, suggesting downregulation of miR548c-3p contributes to the apoptosis of LHON patient RGCs. CONCLUSION: We showed that the downregulation of miR548c-3p plays a critical role in modulating cellular dysfunction and the apoptotic program of RGCs in LHON.

Barriers And Challenges Of Multidisciplinary Teams In Oncology Management: A Scoping Review Protocol.

INTRODUCTION: Multidisciplinary teams (MDTs) are integral to oncology management, involving specialised healthcare professionals who collaborate to develop individualised treatment plans for patients. However, as cancer care grows more complex, MDTs must continually adapt to better address patient needs. This scoping review will explore barriers and challenges MDTs have encountered in the past decade; and propose strategies for optimising their utilisation to overcome these obstacles and improve patient care. METHODS AND ANALYSIS: The scoping review will follow Arksey and O'Malley's framework and begin with a literature search using keywords in electronic databases such as PubMed/MEDLINE, Scopus and PsychINFO, covering the period from January 2013 to December 2022 and limited to English language publications. Four independent reviewers will screen titles and abstracts based on predefined inclusion criteria, followed by full-text review of selected titles. Relevant references cited in the publications will also be examined. A Preferred Reporting Items for Systematic reviews and Meta-Analyses flow diagram will be utilised to illustrate the methodology. Data from selected publications will be extracted, analysed, and categorised for further analysis. ETHICS AND DISSEMINATION: The results of the scoping review will provide a comprehensive overview of the barriers and challenges encountered by oncology MDTs over the past decade. These findings will contribute to the existing literature and provide insights into areas that require improvement in the functioning of MDTs in oncology management. The results will be disseminated through publication in a scientific journal, which will help to share the findings with the wider healthcare community and facilitate further research and discussion in this field. TRIAL REGISTRATION DETAILS: The protocol for this scoping review is registered with Open Science Framework, available at DOI 10.17605/OSF.IO/R3Y8U.

Sulfated disaccharide protects membrane and DNA damages from arginine-rich dipeptide repeats in ALS.

Hexanucleotide repeat expansion in C9ORF72 (C9) is the most prevalent mutation among amyotrophic lateral sclerosis (ALS) patients. The patients carry over ~30 to hundreds or thousands of repeats translated to dipeptide repeats (DPRs) where poly-glycine-arginine (GR) and poly-proline-arginine (PR) are most toxic. The structure-function relationship is still unknown. Here, we examined the minimal neurotoxic repeat number of poly-GR and found that extension of the repeat number led to a loose helical structure disrupting plasma and nuclear membrane. Poly-GR/PR bound to nucleotides and interfered with transcription. We screened and identified a sulfated disaccharide that bound to poly-GR/PR and rescued poly-GR/PR-induced toxicity in neuroblastoma and C9-ALS-iPSC-derived motor neurons. The compound rescued the shortened life span and defective locomotion in poly-GR/PR expressing Drosophila model and improved motor behavior in poly-GR-injected mouse model. Overall, our results reveal structural and toxicity mechanisms for poly-GR/PR and facilitate therapeutic development for C9-ALS.

Next-Generation Sequencing in Lung Cancers-A Single-Center Experience in Taiwan.

Background and Objectives: Lung cancer is a leading cause of cancer mortality in Taiwan. With rapid advancement of targeted therapeutics in non-small cell lung cancers, next-generation sequencing (NGS) is becoming an important tool for biomarker testing. In this study, we describe institutional experience of NGS analysis in non-small cell carcinoma (NSCLC). Materials and Methods: A cohort of 73 cases was identified from the institutional pathology archive in the period between November 2020 and December 2022. Results: Adenocarcinoma was the most common histologic type (91.8%). Most patients presented with stage IIIB and beyond (87.7%). Twenty-nine patients (39.7%) were evaluated at the time of initial diagnosis, while the others had received prior chemotherapy or targeted therapy. The most frequently mutated gene was EGFR (63%), and this was followed by TP53 (50.7%), KRAS (13.7%), RB1 (13.7%), and CDKN2A (13.7%). Clinically actionable mutations associated with a guideline-suggested targeted therapy were identified in 55 cases (75.3%) overall, and in 47.1% of cases excluding EGFR TKI-sensitizing mutation. Biomarkers other than EGFR TKI-sensitizing mutations were compared. Cases without TKI-sensitizing EGFR mutation had more level 1 or 2 biomarkers (excluding EGFR TKI-sensitizing mutations) than cases with TKI-sensitizing EGFR mutations (47.1% versus 20.1%, p = 0.016). Progressive disease was associated with co-occurrence of clinically actionable mutations (20.5% versus 0%, p < 0.05). Eight of the nine cases with co-occurring actionable genetic alternations had an EGFR mutation. After an NGS test, 46.1% of actionable or potentially actionable genetic alternations led to patients receiving a matched therapy. Conclusions: Our study demonstrated that NGS analysis identifies therapeutic targets and may guide treatment strategies in NSCLC. NGS tests may be advantageous over multiple single-gene tests for optimization of treatment plans, especially for those with non-EGFR mutations or those with progressive disease.

The Delivery Model of Perceived Medical Service Quality Based on Donabedian's Framework.

ABSTRACT: The implementation of the National Health Insurance has transformed the medical care landscape in Taiwan, rendering perceived medical service quality (PMSQ) and patient satisfaction significant focal points in medical care management. Past studies mostly focused on the technical aspects of medical care services, while overlooking the patients' perception of services and the delivery process of PMSQ in the medical care experience. This study integrated the theoretical framework of the Donabedian SPO model and the SERVQUAL questionnaire. The survey was conducted among the outpatients of three types of medical institutions in northern Taiwan: academic medical centers, metropolitan hospitals, and local community hospitals. A total of 400 questionnaires were collected, and 315 valid questionnaires remained after eliminating the incomplete ones. This study established a PMSQ delivery model to explore patients' perceptions of medical service quality. It was found that the variable, Assurance, could deliver the PMSQ and enhance the Medical outcome (MO), while improving the variable, Tangible, in medical institutions could not significantly enhance the MO. These findings emphasize the importance of healthcare institutions prioritizing the professional background, demeanor of their healthcare staff, treatment methods, and processes over tangible elements.

Efficient induction of pluripotent stem cells differentiated into mesenchymal stem cell lineages.

BACKGROUND: Mesenchymal stem cells (MSCs) have garnered significant attention in the field of cell-based therapy owing to their remarkable capabilities for differentiation and self-renewal. However, primary tissue-derived MSCs are plagued by various limitations, including constrained tissue sources, arduous and invasive retrieval procedures, heterogeneous cell populations, diminished purity, cellular senescence, and a decline in self-renewal and proliferative capacities after extended expansion. Addressing these challenges, our study focuses on establishing a robust differentiation platform to generate mesenchymal stem cells derived from induced pluripotent stem cells (iMSCs). METHODS: To achieve this, we used a comprehensive methodology involving the differentiation of induced pluripotent stem cells into MSCss. The process was meticulously designed to ensure the expression of key MSC positive markers (CD73, CD90, and CD105) at elevated levels, coupled with the minimal expression of negative markers (CD34, CD45, CD11b, CD19, and HLA-DR). Moreover, the stability of these characteristics was evaluated across 10th generations. RESULTS: Our findings attest to the success of this endeavor. iMSCs exhibited robust expression of positive markers and limited expression of negative markers, confirming their MSC identity. Importantly, these characteristics remained stable even up to the 10th generation, signifying the potential for sustained use in therapeutic applications. Furthermore, our study demonstrated the successful differentiation of iMSCs into osteocytes, chondrocytes, and adipocytes, showcasing their multilineage potential. CONCLUSION: In conclusion, the establishment of induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) presents a significant advancement in overcoming the limitations associated with primary tissue-derived MSCs. The remarkable stability and multilineage differentiation potential exhibited by iMSCs offer a strong foundation for their application in regenerative medicine and tissue engineering. This breakthrough paves the way for further research and development in harnessing the full therapeutic potential of iMSCs.

Identification of phenomic data in the pathogenesis of cancers of the gastrointestinal (GI) tract in the UK biobank.

Gastrointestinal (GI) cancers account for a significant incidence and mortality rates of cancers globally. Utilization of a phenomic data approach allows researchers to reveal the mechanisms and molecular pathogenesis of these conditions. We aimed to investigate the association between the phenomic features and GI cancers in a large cohort study. We included 502,369 subjects aged 37-73 years in the UK Biobank recruited since 2006, followed until the date of the first cancer diagnosis, date of death, or the end of follow-up on December 31st, 2016, whichever occurred first. Socio-demographic factors, blood chemistry, anthropometric measurements and lifestyle factors of participants collected at baseline assessment were analysed. Unvariable and multivariable logistic regression were conducted to determine the significant risk factors for the outcomes of interest, based on the odds ratio (OR) and 95% confidence intervals (CI). The analysis included a total of 441,141 participants, of which 7952 (1.8%) were incident GI cancer cases and 433,189 were healthy controls. A marker, cystatin C was associated with total and each gastrointestinal cancer (adjusted OR 2.43; 95% CI 2.23-2.64). In this cohort, compared to Asians, the Whites appeared to have a higher risk of developing gastrointestinal cancers. Several other factors were associated with distinct GI cancers. Cystatin C and race appear to be important features in GI cancers, suggesting some overlap in the molecular pathogenesis of GI cancers. Given the small proportion of Asians within the UK Biobank, the association between race and GI cancers requires further confirmation.

Exploration of the mechanism of reinfusion of fresh autologous blood in type 2 diabetes mice to induce macrophage polarization and inhibit erythrocyte damage.

AIMS/INTRODUCTION: Type 2 diabetes triggers an inflammatory response that can damage red blood cells. M2 macrophages have inhibitory effects on inflammation, and play an important role in tissue damage repair and fibrosis. Autologous blood transfusion has the potential to inhibit red blood cell damage by mediating macrophage polarization. MATERIALS AND METHODS: Swiss mice were used to establish a suitable type 2 diabetes model, and autologous blood transfusion was carried out. The mice were killed, the blood of the mice was collected and CD14+ monocytes were sorted. The expression levels of phenotypic molecules CD16, CD32 and CD206 in CD14+ monocytes were analyzed by flow cytometry. The proportion of M1 and M2 macrophages were analyzed by flow cytometry. The Q value, P50 , 2,3-diphosphoglycerate and Na+ -K+ -ATPase of red blood cells were detected. The red blood cell osmotic fragility test analyzed the red blood cell osmotic fragility. Western blot analysis was used to analyze the expression changes of erythrocyte surface membrane proteins or transporters erythrocyte membrane protein band 4.1, sphingosine-1-phosphate, glycolipid transfer protein and signal peptide peptidase-like 2A. RESULTS: Autologous blood transfusion induced a significant increase in the number of macrophages. The state and capacity of blood cells improved with autologous blood transfusion. Reinfusion of fresh autologous blood in type 2 diabetes mice made erythrocytes shrink. The expression of erythrocyte-related proteins proved that the erythrocyte injury in the reinfusion of fresh autologous blood + type 2 diabetes group was significantly reduced. CONCLUSION: The reinfusion of fresh autologous blood into the body of patients with type 2 diabetes can induce macrophage polarization to M2, thereby inhibiting red blood cell damage.

Immune infiltration and clinical significance analyses of the cancer-associated fibroblast-related signature in skin cutaneous melanoma.

BACKGROUND: Skin cutaneous melanoma (SKCM) is one of the most aggressive cancers with high mortality rates. Cancer-associated fibroblasts (CAFs) play essential roles in tumor growth, metastasis and the establishment of a pro-tumor microenvironment. This study aimed to establish a CAF-related signature for providing a new perspective for indicating prognosis and guiding therapeutic regimens of SKCM patients. METHODS: In this study, the CAF-related genes were screened out based on melanoma-associated fibroblast markers identified from single-cell transcriptome analysis in the Gene Expression Omnibus (GEO) database and a CAF-related module identified from weighted gene co-expression analysis using The Cancer Genome Atlas (TCGA) dataset. We extracted these gene expression data of SKCM samples from TCGA and constructed a prognostic CAF-related signature. The prediction abilities of the signature for survival prognosis, tumor immune landscape and responses to chemo-/immunotherapies were evaluated in the TCGA-SKCM cohort. RESULTS: We suggested that CAFs were significantly involved in the clinical outcomes of SKCM. A 10-gene CAF-related model was constructed, and the high-CAF risk group exhibited immunosuppressive features and worse prognosis. Patients with high CAF score were more likely to not respond to immune checkpoint inhibitors but were more sensitive to some chemotherapeutic agents, suggesting a potential approach of chemotherapy/anti-CAF combination treatment to improve the SKCM patient response rate of current immunotherapies. CONCLUSIONS: The CAF-related risk score could serve as a robust prognostic indicator and personal assessment of this score could uncover the degree of immunosuppression and provide treatment strategies to improve outcomes in clinical decision-making in SKCM patients.

Leber's hereditary optic neuropathy: Update on the novel genes and therapeutic options.

A maternal inheritance disorder called Leber's hereditary optic neuropathy (LHON) is the most common primary mitochondrial deoxyribonucleic acid (DNA) disorder. In most studies, there are more male patients than female patients, which contradicts the usual pattern in mitochondrial hereditary diseases. This suggests that nuclear DNA (nDNA) may influence the degeneration of retinal ganglion cells (RGCs) in LHON. The primary cause of this is dysfunction in complex I of the electron transport chain, leading to ineffective adenosine triphosphate (ATP) production. In addition to MT-ND4 or MT-ND1 mutations, genes such as PRICKLE3 , YARS2 , and DNAJC30 , which come from nDNA, also play a role in LHON. These three genes affect the electron chain transport differently. PRICKLE3 interacts with ATP synthase (complex V) at Xp11.23, while YARS2 is a tyrosyl-tRNA synthetase 2 involved in mitochondria . DNAJC30 mutations result in autosomal recessive LHON (arLHON). Understanding how genes impact the disease is crucial for developing new treatments. Idebenone has been approved for treating LHON and has shown safety and efficacy in clinical trials. Mesenchymal stem cell-based therapy has also emerged as a potential treatment for LHON by transferring mitochondria into target cells. Gene therapy research focuses on specific gene mutations, and the wild-type ND4 gene target in the adeno-associated viruses (AAV) vector has shown promise in clinical trials as a potential treatment for LHON.