Surgical Excision Combined with Photodynamic Therapy for Squamous Cell Carcinoma Arising in Lupus Vulgaris.

Cutaneous squamous cell carcinoma (SCC) is a common non-melanoma skin cancer (NMSC). Although most cutaneous SCC in people with lighter skin pigmentation as a result of sun damage, patients with underlying conditions such as skin ulcers and chronic inflammation-including conditions such as lupus vulgaris (LV) and chronic discoid lupus erythematosus-are also predisposed to developing SCC. Here we report a case of secondary SCC diagnosed in a 54-year-old patient with 20 years of lupus vulgaris without prior formal systemic treatment, a rarity in clinical practice. Two months ago, the patient developed papules on the right cheek that ulcerated and discharged purulent fluid. Laboratory tests revealed a positive TSPOT result and histopathological examination confirmed granulomatous lesions, supporting the diagnosis of SLE. However, a tissue biopsy unexpectedly revealed a moderately differentiated SCC of the keratinizing type. In this case, we performed surgical excision of the lesion followed by cosmetic closure and adjuvant photodynamic therapy (PDT). Concurrently, the patient underwent systemic anti-tuberculosis treatment. At 6 months post-treatment, no tumour recurrence was observed and the rash associated with lupus erythematosus had also resolved. The patient was satisfied with the treatment outcome.

A case of herpes zoster secondary to monkeypox in a young man.

A 19-year-old young man presented with prodromal symptoms including fever and sore throat, followed by the development of scattered rashes in the perianal and penile regions. Monkeypox (MPX) was confirmed using polymerase chain reaction (PCR) of lesions. On the third day after complete resolution of the initial rash, the patient developed a new rash, which was diagnosed as secondary herpes zoster (HZ). Therefore, clinicians should not only focus on the accurate diagnosis of monkeypox, but also be alert to secondary herpes zoster.

Photodynamic therapy for facial dermatosis papulosa nigra: Efficacy and safety in a preliminary study.

Dermatosis papulosa nigra (DPN) is a type of benign epidermal hyperplasia that affects the appearance of patients and poses a threat to their physical and mental health. Photodynamic therapy (PDT) has been shown to have the advantages of non-invasiveness, efficacy, and low recurrence in the treatment of skin disorders. However, no studies have been reported on the use of PDT for the treatment of DPN. Therefore, we used PDT for the first time to treat DPN and monitor its efficacy. Forty-five patients with DPN diagnosed at the outpatient clinic of Changzhou First People's Hospital were treated with 10 % 5-aminolevulinic acid (ALA) once a week for four consecutive weeks and followed for 3 months. After four treatment sessions, the cure rate among the 45 patients was 71.1 %, and the overall efficacy rate was 93.3 %. The most common adverse reactions were mild erythema, edema, and temporary pigmentation. PDT is expected to become a new and effective treatment for DPN.

A Bibliometric Analysis of Clear Aligner Treatment (CAT) From 2003 to 2023.

Clear aligner treatment (CAT) has been evolving over the past two decades. This study aims to conduct a comprehensive and up-to-date bibliometric analysis of publications related to CAT, presenting the research trends, landscapes, and hot spots in this field. All publications were retrieved from the Web of Science Core Collection from 2003 to 2023. In addition to a general analysis of research landscapes, the following items were analyzed, i.e., countries, institutions, authors, journals, publications, and keywords. A total of 1031 relevant publications were included in this study. From 2003 to the present, the number of publications and citations in this field showed an increasing trend. Italy led in terms of publication counts, and Sichuan University in China had the highest publication counts among institutions. In total, 33 scholars had published a minimum of 10 articles, and the collaborations among them were mostly within each country. The American Journal of Orthodontics and Dentofacial Orthopedics published the most relevant publications. "Predictability of tooth movements," "influencing factors for clinical efficacy," "biomechanics," and "patients' perception and periodontal health" stood out as the core research focus on CAT. Our study identified the most influential countries, institutions and authors, and their cooperative relationships, and detected hot research topics on CAT, calling for more high-quality international collaborative research in the future.

High-performance Ag-TiO2 nanoparticle composite catalyst synthesized by pulsed laser ablation in liquid: properties, mechanism and preparation studies.

Precious metal doping can effectively improves the catalytic performance of TiO2. In this study, pulsed laser ablation in liquid (PLAL) is employed to integrate preparation with doping and control composite nanoparticle products by adjusting the laser action time to synthesise Ag-TiO2 composite nanoparticles with high catalytic performance. The generation and evolution of Ag-TiO2 nanoparticles are investigated by analysing particle size, microscopic morphology, crystalline phase, and other characteristics. The generation and doped-morphology evolution of composite nanoparticles are simulated based on thermodynamics, and the optimisation of Ag-doped structure on the composite nanomaterials is investigated based on density functional theory. The effect of Ag-TiO2 structural properties on its performance is examined under different catalytic conditions to determine optimal degradation conditions. In this study, the effect of laser ablation time on the doped structure during PLAL is analysed, which is of further research significance in exploring the structural evolution law of laser and composite nanoparticles, multi-variate catalytic performance testing, reduction of photogenerated carrier complexation rate, and expansion of its spectral absorption range, thereby providing the basis for practical production.

Single-cell transcriptomic analyses of mouse idh1 mutant growth plate chondrocytes reveal distinct cell populations responsible for longitudinal growth and enchondroma formation.

Enchondromas are a common tumor in bone that can occur as multiple lesions in enchondromatosis, which is associated with deformity of the effected bone. These lesions harbor mutations in IDH and driving expression of a mutant Idh1 in Col2 expressing cells in mice causes an enchondromatosis phenotype. In this study we compared growth plates from E18.5 mice expressing a mutant Idh1 with control littermates using single cell RNA sequencing. Data from Col2 expressing cells were analyzed using UMAP and RNA pseudo-time analyses. A unique cluster of cells was identified in the mutant growth plates that expressed genes known to be upregulated in enchondromas. There was also a cluster of cells that was underrepresented in the mutant growth plates that expressed genes known to be important in longitudinal bone growth. Immunofluorescence showed that the genes from the unique cluster identified in the mutant growth plates were expressed in multiple growth plate anatomic zones, and pseudo-time analysis also suggested these cells could arise from multiple growth plate chondrocyte subpopulations. This data identifies subpopulations of cells in control and mutant growth plates, and supports the notion that a mutant Idh1 alters the subpopulations of growth plate chondrocytes, resulting a subpopulation of cells that become enchondromas at the expense of other populations that contribute to longitudinal growth.

The prevalence and mechanisms of heteroresistance to ceftazidime/avibactam in KPC-producing Klebsiella pneumoniae.

OBJECTIVES: To investigate the prevalence and mechanisms of ceftazidime/avibactam heteroresistance in KPC-producing Klebsiella pneumoniae (KPC-KP) isolates, as well as the role of heteroresistance in the transition of ceftazidime/avibactam susceptibility to resistance. METHODS: Clinical KPC-KP isolates were obtained from a tertiary hospital in China from 2016 to 2017 and 2019 to 2020. Antimicrobial susceptibility was determined by the broth microdilution method. Population analysis profiles were used to assess ceftazidime/avibactam heteroresistance. WGS and molecular cloning were conducted to reveal heteroresistance mechanisms and molecular characteristics. RESULTS: The findings indicated that the transition of ceftazidime/avibactam susceptibility to resistance during the treatment of KPC-KP infection is primarily attributed to the heteroresistance exhibited by KPC-KP isolates towards ceftazidime/avibactam. Among 355 ceftazidime/avibactam-susceptible KPC-KP isolates (indicating a resistance rate of 0%), 41 (11.55%) exhibited ceftazidime/avibactam heteroresistance, with the primary mechanism being the presence of KPC mutant subpopulations. These KPC variants, arising from point mutations, deletions and insertions, significantly increased ceftazidime/avibactam resistance while alongside enhanced carbapenem susceptibility. Notably, 11 new KPC variants were identified. Furthermore, four heteroresistant isolates were caused by mixed infection involving subpopulations carrying NDM-1 or NDM-5. Phylogenetic analysis indicated that the clonal spread of ST11-KL64 KPC-KP may be correlated with the prevalence of heteroresistance. CONCLUSIONS: Ceftazidime/avibactam heteroresistance, primarily driven by pre-existing KPC variants, underscores the importance of considering heteroresistance in ceftazidime/avibactam therapeutics. Awareness of these dynamics is crucial for the effective and sustainable clinical application of ceftazidime/avibactam.

PAM-1: an antimicrobial peptide with promise against ceftazidime-avibactam resistant Escherichia coli infection.

Introduction: Antibiotic misuse and overuse have led to the emergence of carbapenem-resistant bacteria. The global spread of resistance to the novel antibiotic combination ceftazidime-avibactam (CZA) is becoming a severe problem. Antimicrobial peptide PAM-1 offers a novel approach for treating infections caused by antibiotic-resistant bacteria. This study explores its antibacterial and anti-biofilm activities and mechanisms against CZA-resistant Escherichia. Coli (E. coli), evaluating its stability and biosafety as well. Methods: The broth microdilution method, growth curve analysis, crystal violet staining, scanning electron microscopy, and propidium iodide staining/N-phenyl-1-naphthylamine uptake experiments were performed to explore the antibacterial action and potential mechanism of PAM-1 against CZA-resistant E. coli. The biosafety in diverse environments of PAM-1 was evaluated by red blood cell hemolysis, and cytotoxicity tests. Its stability was further assessed under different temperatures, serum concentrations, and ionic conditions using the broth microdilution method to determine its minimum inhibitory concentration (MIC). Galleria mellonella infection model and RT-qPCR were used to investigate the in vivo antibacterial and anti-inflammatory effects. Results and discussion: In vitro antibacterial experiments demonstrated that the MICs of PAM-1 ranged from 2 to 8 µg/mL, with its effectiveness sustained for a duration of 24 h. PAM-1 exhibited significant antibiofilm activities against CZA-resistant E. coli (p < 0.05). Furthermore, Membrane permeability test revealed that PAM-1 may exert its antibacterial effect by disrupting membrane integrity by forming transmembrane pores (p < 0.05). Red blood cell hemolysis and cytotoxicity tests revealed that PAM-1 exerts no adverse effects at experimental concentrations (p < 0.05). Moreover, stability tests revealed its effectiveness in serum and at room temperature. The Galleria mellonella infection model revealed that PAM-1 can significantly improve the survival rate of Galleria mellonella (>50%)for in vivo treatment. Lastly, RT-qPCR revealed that PAM-1 downregulates the expression of inflammatory cytokines (p < 0.05). Overall, our study findings highlight the potential of PAM-1 as a therapeutic agent for CZA-resistant E. coli infections, offering new avenues for research and alternative antimicrobial therapy strategies.

Correlation between thyroid hormone sensitivity and the risk of polycystic ovary syndrome.

OBJECTIVE: There has been some confusion in earlier research on the connection between thyroid function and polycystic ovary syndrome (PCOS). This research is aimed to probe into the correlation between thyroid condition and the risk of PCOS from a new standpoint of thyroid hormone sensitivity. METHODS: This research comprised 415 females with PCOS from Drum Tower Hospital Affiliated with the Medical School of Nanjing University, and 137 non-PCOS individuals were selected as the normal control. Based on free thyroxine (FT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH), we calculated the thyroid hormone sensitivity indices, which consist of Thyroid Feedback Quantile-based Index (TFQI), Thyroid-stimulating Hormone Index (TSHI), Thyrotroph Thyroxine Resistance Index (TT4RI) and Free Triiodothyronine /Free thyroxine (FT3/FT4). The binary logistic regression model was adopted to investigate the correlation between thyroid hormone sensitivity indices with the risk of PCOS. Pearson or Spearman correlation analysis was employed to explore the association among thyroid-related measures with metabolic parameters in PCOS. RESULTS: Results of this research showed that females with PCOS had rising TFQI, TSHI, TT4RI, and FT3/FT4 levels compared with the control group. After adjustment for the impact of various covariates, there was no significant correlation between FT3/FT4 and the risk of PCOS; However, the odds ratio of the third and fourth vs. the first quartile of TFQI were 3.57(95% confidence interval [CI]:1.08,11.87) and 4.90(95% CI:1.38,17.38) respectively; The odds ratio of the fourth vs. the first quartile of TSHI was 5.35(95% CI:1.48,19.37); The odds ratio of the second vs. the first quartile of TT4RI was 0.27(95%CI 0.09,0.82). In addition, no significant correlation was observed between thyroid-related measures and metabolic measures in females with PCOS. CONCLUSIONS: A reduction in the sensitivity of central thyroid hormone is closely correlated with a higher risk of PCOS. Further research is necessary to corroborate our findings and the supporting mechanisms.

Extracellular vesicle-mediated communication between CD8+ cytotoxic T cells and tumor cells.

Tumors pose a significant global public health challenge, resulting in numerous fatalities annually. CD8+ T cells play a crucial role in combating tumors; however, their effectiveness is compromised by the tumor itself and the tumor microenvironment (TME), resulting in reduced efficacy of immunotherapy. In this dynamic interplay, extracellular vesicles (EVs) have emerged as pivotal mediators, facilitating direct and indirect communication between tumors and CD8+ T cells. In this article, we provide an overview of how tumor-derived EVs directly regulate CD8+ T cell function by carrying bioactive molecules they carry internally and on their surface. Simultaneously, these EVs modulate the TME, indirectly influencing the efficiency of CD8+ T cell responses. Furthermore, EVs derived from CD8+ T cells exhibit a dual role: they promote tumor immune evasion while also enhancing antitumor activity. Finally, we briefly discuss current prevailing approaches that utilize functionalized EVs based on tumor-targeted therapy and tumor immunotherapy. These approaches aim to present novel perspectives for EV-based tumor treatment strategies, demonstrating potential for advancements in the field.

Role of extracellular vesicles in castration-resistant prostate cancer.

Prostate cancer (PCa) is a common health threat to men worldwide, and castration-resistant PCa (CRPC) is the leading cause of PCa-related deaths. Extracellular vesicles (EVs) are lipid bilayer compartments secreted by living cells that are important mediators of intercellular communication. EVs regulate the biological processes of recipient cells by transmitting heterogeneous cargoes, contributing to CRPC occurrence, progression, and drug resistance. These EVs originate not only from malignant cells, but also from various cell types within the tumor microenvironment. EVs are widely dispersed throughout diverse biological fluids and are attractive biomarkers derived from noninvasive liquid biopsy techniques. EV quantities and cargoes have been tested as potential biomarkers for CRPC diagnosis, progression, drug resistance, and prognosis; however, technical barriers to their clinical application continue to exist. Furthermore, exogenous EVs may provide tools for new therapies for CRPC. This review summarizes the current evidence on the role of EVs in CRPC.

Unravelling Childhood Tinea Capitis: A Multi-Dimensional Investigation Using Dermoscopy, Scanning Electron Microscopy and Mass Spectrometry.

Tinea capitis, a common cutaneous fungal infection, shows an increasing prevalence with the increasing number of pets. We present tinea capitis in a 4-year-old girl presenting without typical symptoms such as alopecia or hair breakage. After a comprehensive evaluation including dermoscopy, Wood's light, direct KOH fluorescent staining, scanning electron microscopy, fungal culture and mass spectrometry analysis, a diagnosis of tinea capitis infected Microsporum canis carried by domestic cats was made. We preliminarily explored the two modes of hair erosion by tinea capitis fungi and analyzed the possibility of the feature in this case. This case highlights the importance of accurate diagnosis and appropriate therapeutic intervention in cases of paediatric tinea capitis, particularly in households with resident pets.

Effect of Strain Rate, Temperature, Vacancy, and Microcracks on Mechanical Properties of 8-16-4 Graphyne.

The 8-16-4 graphyne, a recently identified two-dimensional carbon allotrope, exhibits distinctive mechanical and electrical properties, making it a candidate material for flexible electronic applications. This study endeavors to enhance our comprehension of the fracture behavior and mechanical properties of 8-16-4 graphyne. The mechanical properties of 8-16-4 graphyne were evaluated through molecular dynamics simulations, examining the impact of boundary conditions, temperature, and strain rate, as well as the coupled interactions between temperature, vacancy defects, and microcracks. The findings reveal that 8-16-4 graphyne undergoes fracture via the cleavage of ethylene bonds at a critical strain value of approximately 0.29. Variations in boundary conditions and strain rate influence the fidelity of tensile simulation outcomes. Temperature, vacancy concentration, and the presence of microcracks markedly affect the mechanical properties of 8-16-4 graphyne. In contrast to other carbon allotropes, 8-16-4 graphyne exhibits a diminished sensitivity to vacancy defects in its mechanical performance. However, carbon vacancies at particular sites are more prone to initiating cracks. Furthermore, pre-existing microcracks within the material can potentially alter the fracture mode.

Disease progression and clinical outcomes in latent osteoarthritis phenotypes: Data from the Osteoarthritis Initiative.

The prevalence of knee osteoarthritis (OA) is widespread and the heterogeneous patient factors and clinical symptoms in OA patients impede developing personalized treatments for OA patients. In this study, we used unsupervised and supervised machine learning to organize the heterogeneity in knee OA patients and predict disease progression in individuals from the Osteoarthritis Initiative (OAI) dataset. We identified four distinct knee OA phenotypes using unsupervised learning that were defined by nutrition, disability, stiffness, and pain (knee and back) and were strongly related to disease fate. Interestingly, the absence of supplemental vitamins from an individual's diet was protective from disease progression. Moreover, we established a phenotyping tool and prognostic model from 5 variables (WOMAC disability score of the right knee, WOMAC total score of the right knee, WOMAC total score of the left knee, supplemental vitamins and minerals frequency, and antioxidant combination multivitamins frequency) that can be utilized in clinical practice to determine the risk of knee OA progression in individual patients. We also developed a prognostic model to estimate the risk for total knee replacement and provide suggestions for modifiable variables to improve long-term knee health. This combination of unsupervised and supervised data-driven tools provides a framework to identify knee OA phenotype in a clinical scenario and personalize treatment strategies.

Intercalation chemistry engineering strategy enabled high mass loading and ultrastable electrodes for High-Performance aqueous electrochemical energy storage devices.

Aqueous electrochemical energy storage devices (AEESDs) are considered one of the most promising candidates for large-scale energy storage infrastructure due to their high affordability and safety. Developing electrodes with the merits of high energy density and long lifespan remains a challenging issue toward the practical application of AEESDs. Research attempts at electrode materials, nanostructure configuration, and electronic engineering show the limitations due to the inherent contradictions associated with thicker electrodes and ion-accessible kinetics. Herein, we propose an intercalation chemistry engineering strategy to enhance the electrolyte ion (de)intercalation behaviors during the electrochemical charge-discharge. To validate this strategy, the prototypical model of a high-mass-loading MnO2-based electrode is used with controlled intercalation of Na+ and H2O. Theoretical and experimental results reveal that an optimal content of Na+ and H2O on the MnO2-based electrode exhibits superior electrochemical performance. Typically, the resultant electrode exhibits an impressive areal capacitance of 1551 mF/cm2 with a mass loading of 9.7 mg/cm2 (at 1 mA/cm2). Furthermore, the assembled full-cell with obtained MnO2-based electrode delivers a high energy density of 0.12 mWh/cm2 (at 20.02 mW/cm2) and ultra-high cycling stability with a capacitance retention percentage of 89.63 % (345 mF/cm2) even after 100,000 cycles (tested over 72 days).

The Free Triiodothyronine, Gamma-Glutamyl Transpeptidase and Spontaneous Bacterial Peritonitis Index: A Novel Model for Predicting 1-Year Mortality in Patients with HBV-Related Hepatic Encephalopathy.

Background and Aims: Hepatic encephalopathy (HE) is characterized by neuropsychiatric manifestations in patients with decompensated cirrhosis (DC) and/or liver failure. This study aimed to investigate the predictive value of thyroid hormone in patients with HE. Methods: Patients with DC and HE were enrolled, and multivariate logistic analysis was conducted to analyze the risk factors for 1-year mortality. Results: Among the 81 patients with HBV-related DC and HE, 9 (11.1%) died within 3 months, and 15 (18.5%) died within the first year. More patients with FT3 < 3.5pmol/L had ascites (33.3% vs 8.9%, P<0.01) and higher model for end-stage liver disease (MELD) (Z=3.669, P<0.01). Additionally, free triiodothyronine (FT3) levels were lower in the non-survivor group (P<0.01). FT3 exhibited a negative correlation with international normalized ratio and MELD (both P<0.05). Multivariate analysis revealed that FT3, gamma-glutamyl transpeptidase (GGT), and spontaneous bacterial peritonitis (SBP) were independent risk factors for 1-year mortality of HE. A new model incorporating FT3, GTT, and SBP demonstrated superiority to MELD based on the AUROC (0.9 and 0.752, P=0.04). Conclusion: Low FT3, but not thyroid-stimulating hormone and free tetraiodothyronine, was identified as an independent risk factor for 1-year mortality in patients with DC and HE. The newly proposed prognostic model, which includes FT3, GTT, and SBP, holds significant predictive value.

Prospective study of an adalimumab combined with partial enteral nutrition in the induction period of Crohn's disease.

BACKGROUND: Adalimumab monotherapy can suppress gut inflammation and induce remission in active Crohn's disease but has some limitations. Exclusive enteral nutrition (EEN) is recommended for patients with mild to moderate Crohn's disease (CD), but implementation is challenging. AIM: To evaluate the effectiveness of adalimumab combined with partial enteral nutrition (PEN) in the induction therapy for Crohn's disease. METHODS: A prospective cohort study was designed and a total of 56 patients with active CD who met the criteria for enteral nutrition (EN) treatment in our hospital were selected. The baseline data of all patients were collected including age, sex and other general information. The changes in fecal calprotectin, C-reactive protein (CRP), albumin(Alb), hemoglobin (Hb), platelets (Plt), erythrocyte sedimentation rate (ESR), Crohn's disease activity index score (CDAI), simple endoscopic score (SES-CD) and body mass index (BMI) were compared between the adalimumab combined with enteral nutrition (ADA+EN) group (N = 37) the adalimumab group (ADA) (N = 19) at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated. Then the ADA+EN group was divided into an adalimumab combined with exclusive enteral nutrition subgroup (ADA+EEN) and an adalimumab combined with partial nutrition subgroup (ADA+PEN) according to enteral nutrition intake. The changes in fecal calprotectin, CRP, Alb, Hb, Plt, ESR and CDAI, SES-CD and BMI were compared between the  ADA+EEN group and the ADA+PEN group at week 0 (W0) and treatment outcomes at week 12(W12). The differences between the two groups before and after treatment were evaluated. To evaluate the effectiveness of the two treatments on patients' quality of life, nutritional recovery and body composition, patients in the ADA+EN group were needed to complete the Inflammatory Bowel Disease Questionnaire (IBDQ), EQ-5D-5L, the EuroQol visual analogue scale (EQ-VAS) and body composition analysis.A total of 28 patients completed all questionnaires and body composition analyses at week 0 and week 12, including 10 patients in the ADA+EEN group and 18 patients in the ADA+PEN group, respectively. The differences of in IBDQ, EQ-5D-5L and body composition analysis were compared between the two groups at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated. RESULTS: These investigated indexes such as calprotectin, Hb, Plt, ESR, Alb, BMI, CRP, CDAI and SES-CD scores were significantly different before and after treatment  in the ADA+EN group (p < 0.01). However, fecal calprotectin, Hb, SES-CD scores and Alb in the ADA group were not statistically significantly different from W0 to W12 (p > 0.05). The fecal calprotectin and CDAI scores in the ADA+EN group were significantly lower than those in the ADA group after treatment. The differences in all factors before and after treatment between the ADA+PEN group and the ADA+EEN group were statistically significant (p < 0.05). However, there was no significant difference between the two groups at week 12 (p > 0.05). CONCLUSION: Adalimumab combined with EN are more effective than ADA monotherapy in terms of endoscopy and clinical remission. By comparing the investigated indicators such as calprotectin, Hb, Plt, ESR ,CRP and SES-CD scores, it was proven that adalimumab combined with partial enteral nutrition or exclusive enteral nutrition has the same remission effect in induced Crohn's disease. The combination of biological agents and partial nutrition can improve medical order compliance, psychological burden and quality of life. Therefore, adalimumab combined with partial nutrition can be used as the first-line treatment for CD induced remission.

Development and Validation of a Nomogram for Predicting Postoperative Early Relapse and Survival in Hepatocellular Carcinoma.

BACKGROUND: Early relapse after hepatectomy presents a significant challenge in the treatment of hepatocellular carcinoma (HCC). The aim of this study was to construct and validate a novel nomogram model for predicting early relapse and survival after hepatectomy for HCC. PATIENTS AND METHODS: We conducted a large-scale, multicenter retrospective analysis of 1,505 patients with surgically treated HCC from 4 medical centers. All patients were randomly divided into either the training cohort (n=1,053) or the validation cohort (n=452) in a 7:3 ratio. A machine learning-based nomogram model for prediction of HCC was established by integrating multiple risk factors that influence early relapse and survival, which were identified from preoperative clinical data and postoperative pathologic characteristics of the patients. RESULTS: The median time to early relapse was 7 months, whereas the median time from early relapse to death was only 19 months. The concordance indexes of the postoperative nomogram for predicting disease-free survival and overall survival were 0.741 and 0.739, respectively, with well-calibrated curves demonstrating good consistency between predicted and observed outcomes. Moreover, the accuracy and predictive performance of the postoperative nomograms were significantly superior to those of the preoperative nomogram and the other 7 HCC staging systems. The patients in the intermediate- and high-risk groups of the model had significantly higher probabilities of early and critical recurrence (P<.001), whereas those in the low-risk group had higher probabilities of late and local recurrence (P<.001). CONCLUSIONS: This postoperative nomogram model can better predict early recurrence and survival and can serve as a useful tool to guide clinical treatment decisions for patients with HCC.

Disease progression and clinical outcomes in latent osteoarthritis phenotypes: Data from the Osteoarthritis Initiative.

The prevalence of knee osteoarthritis (OA) is widespread and the heterogeneous patient factors and clinical symptoms in OA patients impede developing personalized treatments for OA patients. In this study, we used unsupervised and supervised machine learning to organize the heterogeneity in knee OA patients and predict disease progression in individuals from the Osteoarthritis Initiative (OAI) dataset. We identified four distinct knee OA phenotypes using unsupervised learning that were defined by nutrition, disability, stiffness, and pain (knee and back) and were strongly related to disease fate. Interestingly, the absence of supplemental vitamins from an individual's diet was protective from disease progression. Moreover, we established a phenotyping tool and prognostic model from 5 variables (WOMAC disability score of the right knee, WOMAC total score of the right knee, WOMAC total score of the left knee, supplemental vitamins and minerals frequency, and antioxidant combination multivitamins frequency) that can be utilized in clinical practice to determine the risk of knee OA progression in individual patients. We also developed a prognostic model to estimate the risk for total knee replacement and provide suggestions for modifiable variables to improve long-term knee health. This combination of unsupervised and supervised data-driven tools provides a framework to identify knee OA phenotype in a clinical scenario and personalize treatment strategies.