Exploring the potential of isorhapontigenin: attenuating Staphylococcus aureus virulence through MgrA-mediated regulation.

The emerging prevalence of drug-resistant Staphylococcus aureus isolates underscores the urgent need for alternative therapeutic strategies due to the declining effectiveness of traditional antibiotics in clinical settings. MgrA, a key virulence regulator in S. aureus, orchestrates the expression of numerous virulence factors. Here, we report the discovery of isorhapontigenin, a methoxylated analog of resveratrol, as a potential anti-virulence agent against S. aureus. Isorhapontigenin effectively inhibits the hemolytic activity of S. aureus in a non-bactericidal manner. Additionally, it significantly reduces the cytotoxicity of S. aureus and impairs its ability to survive in macrophages. Mechanistically, isorhapontigenin modulates the expression of virulence factors, dose-dependently downregulating hla and upregulating the MgrA-regulated gene spa. Electrophoretic mobility shift assays demonstrated that isorhapontigenin inhibits the binding of MgrA to the hla promoter in a dose-dependent manner. Thermal shift assays confirmed the direct interaction between isorhapontigenin and the MgrA protein. The in vivo experiments demonstrated that isorhapontigenin significantly reduced the area of skin abscesses and improved survival in a pneumonia model while decreasing bacterial burden and inflammation in the lungs. In conclusion, isorhapontigenin holds potential as a candidate drug for further development as an anti-virulence agent for treating S. aureus infections. IMPORTANCE: The emergence of antibiotic-resistant Staphylococcus aureus strains presents a formidable challenge to public health, necessitating novel approaches in combating these pathogens. Traditional antibiotics are becoming increasingly ineffective, leading to a pressing need for innovative therapeutic strategies. In this study, targeting virulence factors that play a crucial role in the pathogenesis of bacterial infections offers a promising alternative to circumvent resistance mechanisms. The discovery of isorhapontigenin as an inhibitor of S. aureus virulence represents a significant advance in anti-virulence therapy.

Diclofenac sodium effectively inhibits the biofilm formation of Staphylococcus epidermidis.

Staphylococcus epidermidis is an opportunistic pathogen commonly implicated in medical device-related infections. Its propensity to form biofilms not only leads to chronic infections but also exacerbates the issue of antibiotic resistance, necessitating high-dose antimicrobial treatments. In this study, we explored the use of diclofenac sodium, a non-steroidal anti-inflammatory drug, as an anti-biofilm agent against S. epidermidis. In this study, crystal violet staining and confocal laser scanning microscope analysis showed that diclofenac sodium, at subinhibitory concentration (0.4 mM), significantly inhibited biofilm formation in both methicillin-susceptible and methicillin-resistant S. epidermidis isolates. MTT assays demonstrated that 0.4 mM diclofenac sodium reduced the metabolic activity of biofilms by 25.21-49.01% compared to untreated controls. Additionally, the treatment of diclofenac sodium resulted in a significant decrease (56.01-65.67%) in initial bacterial adhesion, a crucial early phase of biofilm development. Notably, diclofenac sodium decreased the production of polysaccharide intercellular adhesin (PIA), a key component of the S. epidermidis biofilm matrix, in a dose-dependent manner. Real-time quantitative PCR analysis revealed that diclofenac sodium treatment downregulated biofilm-associated genes icaA, fnbA, and sigB and upregulated negative regulatory genes icaR and luxS, providing potential mechanistic insights. These findings indicate that diclofenac sodium inhibits S. epidermidis biofilm formation by affecting initial bacterial adhesion and the PIA synthesis. This underscores the potential of diclofenac sodium as a supplementary antimicrobial agent in combating staphylococcal biofilm-associated infections.

Longitudinal ultrasound-based AI model predicts axillary lymph node response to neoadjuvant chemotherapy in breast cancer: a multicenter study.

OBJECTIVES: Developing a deep learning radiomics model from longitudinal breast ultrasound and sonographer's axillary ultrasound diagnosis for predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer. METHODS: Breast cancer patients undergoing NAC followed by surgery were recruited from three centers between November 2016 and December 2022. We collected ultrasound images for extracting tumor-derived radiomics and deep learning features, selecting quantitative features through various methods. Two machine learning models based on random forest were developed using pre-NAC and post-NAC features. A support vector machine integrated these data into a fusion model, evaluated via the area under the curve (AUC), decision curve analysis, and calibration curves. We compared the fusion model's performance against sonographer's diagnosis from pre-NAC and post-NAC axillary ultrasonography, referencing histological outcomes from sentinel lymph node biopsy or axillary lymph node dissection. RESULTS: In the validation cohort, the fusion model outperformed both pre-NAC (AUC: 0.899 vs. 0.786, p < 0.001) and post-NAC models (AUC: 0.899 vs. 0.853, p = 0.014), as well as the sonographer's diagnosis of ALN status on pre-NAC and post-NAC axillary ultrasonography (AUC: 0.899 vs. 0.719, p < 0.001). Decision curve analysis revealed patient benefits from the fusion model across threshold probabilities from 0.02 to 0.98. The model also enhanced sonographer's diagnostic ability, increasing accuracy from 71.9% to 79.2%. CONCLUSION: The deep learning radiomics model accurately predicted the ALN response to NAC in breast cancer. Furthermore, the model will assist sonographers to improve their diagnostic ability on ALN status before surgery. CLINICAL RELEVANCE STATEMENT: Our AI model based on pre- and post-neoadjuvant chemotherapy ultrasound can accurately predict axillary lymph node metastasis and assist sonographer's axillary diagnosis. KEY POINTS: Axillary lymph node metastasis status affects the choice of surgical treatment, and currently relies on subjective ultrasound. Our AI model outperformed sonographer's visual diagnosis on axillary ultrasound. Our deep learning radiomics model can improve sonographers' diagnosis and might assist in surgical decision-making.

A de novo Mutation (p.Gln277X) of Cyclin D2 is Responsible for a Child with Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome.

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH), a type of overgrowth syndrome, is characterized by progressive megalencephaly, cortical brain malformations, and distal limb anomalies. Previous studies have revealed that the overactivity of the phosphatidylinositol 3-kinase-Protein kinase B pathway and the increased cyclin D2 (CCND2) expression were the main factors contributing to this disease. Here, we present the case of a patient who exhibited megalencephaly, polymicrogyria, abnormal neuronal migration, and developmental delay. Serum tandem mass spectrometry and chromosome examination did not detect any metabolic abnormalities or copy number variants. However, whole-exome sequencing and Sanger sequencing revealed a de novo nonsense mutation (NM_001759.3: c.829C>T; p.Gln277X) in the CCND2 gene of the patient. Bioinformatics analysis predicted that this mutation may disrupt the structure and surface charge of the CCND2 protein. This disruption could potentially prevent polyubiquitination of CCND2, leading to its resistance against degradation. Consequently, this could drive cell division and growth by altering the activity of key cell cycle regulatory nodes, ultimately contributing to the development of MPPH. This study not only presents a new case of MPPH and expands the mutation spectrum of CCND2 but also enhances our understanding of the mechanisms connecting CCND2 with overgrowth syndromes.

Accuracy of ultrasound-guided fine-needle aspiration for small cervical lymph nodes: A retrospective review of 505 cases.

Purpose: The overall diagnostic value of fine-needle aspiration (FNA) is not as excellent as that of core needle biopsy (CNB). Limited research has investigated small cervical lymph nodes inaccessible to ultrasound-guided CNB due to technical challenges associated with their small size. Therefore, this study aimed to evaluate the accuracy of ultrasound-guided FNA in determining the etiology of small cervical lymph nodes. Methods: A retrospective analysis was conducted on patients who underwent FNA between May 2018 and May 2021 at our hospital. Cytological, histopathological, and clinical follow-up data were analyzed. The diagnostic yield of FNA was assessed based on sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy calculations. Results: This study included 505 patients, each with a small cervical lymph node under evaluation (total number of lymph nodes: 505). The average maximal diameter of the lymph nodes was 14.6 ± 6.2 mm. According to the Sydney system, the cytology results were as follows: Category I in 26 lymph nodes (5.1 %); Category II in 269 (53.3 %); Category III in 35 (6.9 %); Category IV in 17 (3.4 %); and Category V in 158 (31.3 %). We identified 212 malignant cases (203 metastases and 9 lymphomas) and 293 benign lymph nodes. FNA achieved high sensitivity (88.8 %), specificity (99.6 %), PPV (99.4 %), NPV (91.8 %), and overall accuracy (94.8 %) in determining the etiology of small cervical lymph nodes. Conclusion: FNA cytology is suitable for small lesions inaccessible by CNB and provides a diagnostic basis for implementing clinically appropriate treatment measures.

Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant immune checkpoint blockade (ICB) combined with chemoradiotherapy offers high pathologic complete response (pCR) rate for patients with locally advanced esophageal squamous cell carcinomas (ESCC). But the dynamic tumor immune microenvironment modulated by such neoadjuvant therapy remains unclear. PATIENTS AND METHODS: A total of 41 patients with locally advanced ESCC were recruited. All patients received neoadjuvant toripalimab combined with concurrent chemoradiotherapy. Matched pre- and post-treatment tissues were obtained for fluorescent multiplex immunohistochemistry (mIHC) and IHC analyses. The densities and spatial distributions of immune cells were determined by HALO modules. The differences of immune cell patterns before and after neoadjuvant treatment were investigated. RESULTS: In the pre-treatment tissues, more stromal CD3 + FoxP3 + Tregs and CD86+/CD163 + macrophages were observed in patients with residual tumor existed in the resected lymph nodes (pN1), compared with patients with pCR. The majority of macrophages were distributed in close proximity to tumor nest in pN1 patients. In the post-treatment tissues, pCR patients had less CD86 + cell infiltration, whereas higher CD86 + cell density was significantly associated with higher tumor regression grades (TRG) in non-pCR patients. When comparing the paired pre- and post-treatment samples, heterogeneous therapy-associated immune cell patterns were found. Upon to the treatment, CD3 + T lymphocytes were slightly increased in pCR patients, but markedly decreased in non-pCR patients. In contrast, a noticeable increase and a less obvious decrease of CD86 + cell infiltration were respectively depicted in non-pCR and pCR patients. Furthermore, opposite trends of the treatment-induced alterations of CD8 + and CD15 + cell infiltrations were observed between pN0 and pN1 patients. CONCLUSIONS: Collectively, our data demonstrate a comprehensive picture of tumor immune landscape before and after neoadjuvant ICB combined with chemoradiotherapy in ESCC. The infiltration of CD86 + macrophage may serve as an unfavorable indicator for neoadjuvant toripalimab combined with chemoradiotherapy.

New lignans from Phyllanthodendron dunnianum.

A new lignan phyllanins A (1) and a lignan phyllanins B (2) for which the absolute configuration was determined for the first time, along with four known lignans (3-6) were isolated from the branch and leaf extracts of Phyllanthodendron dunnianum. Their planar structures were mainly determined by a combination of 1D and 2D NMR, HRESIMS spectral analyses, and the absolute configurations of the compounds 1 and 2 were established by DFT GIAO 13C NMR and electronic circular dichroism (ECD) calculations. In addition, all these six lignans were firstly tested for the antibacterial activities against MRSA, Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli. Among these compounds, 2 and 5 showed potential antibacterial activities against MRSA and S. aureus with MIC values of 4 and 8 µg/mL, respectively.

Enhancing the biosynthesis of taxadien-5α-yl-acetate in Escherichia coli by combinatorial metabolic engineering approaches.

Biosynthesis of paclitaxel (Taxol™) is a hot topic with extensive and durable interests for decades. However, it is severely hindered due to the very low titers of intermediates. In this study, Escherichia coli was employed to de novo synthesize a key intermediate of paclitaxel, taxadien-5α-yl-acetate (T5OAc). Plasmid-based pathway reconstruction and optimization were conducted for T5OAc production. The endogenous methylerythritol phosphate pathway was enhanced to increase the precursor supply. Three taxadien-5α-ol O-acetyltransferases were tested to obtain the best enzyme for the acetylation step. Metabolic burden was relieved to restore cell growth and promote production through optimizing the plasmid production system. In order to achieve metabolic balance, the biosynthesis pathway was regulated precisely by multivariate-modular metabolic engineering. Finally, in a 5-L bioreactor, the T5OAc titer was enhanced to reach 10.9 mg/L. This represents an approximately 272-fold increase in production compared to the original strain, marking the highest yield of T5OAc ever documented in E. coli, which is believed to be helpful for promoting the progress of paclitaxel biosynthesis.

[A new cucurbitane glycoside from Picrorhiza scrophulariiflora].

Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.

Interfacial Engineering of MoS2@CoS2 Heterostructure Electrocatalysts for Effective pH-Universal Hydrogen Evolution Reaction.

The practical utilization of the hydrogen evolution reaction (HER) necessitates the creation of electrocatalysts that are both efficient and abundant in earth elements, capable of operating effectively within a wide pH range. However, this objective continues to present itself as an arduous obstacle. In this research, we propose the incorporation of sulfur vacancies in a novel heterojunction formed by MoS2@CoS2, designed to exhibit remarkable catalytic performances. This efficacy is attributed to the advantageous combination of the low work function and space charge zone at the interface between MoS2 and CoS2 in the heterojunction. The MoS2@CoS2 heterojunction manifests outstanding hydrogen evolution activity over an extensive pH range. Remarkably, achieving a current density of 10 mA cm-2 in aqueous solutions 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline (PBS), respectively, requires only an overpotential of 48, 62, and 164 mV. The Tafel slopes for each case are 43, 32, and 62 mV dec-1, respectively. In this study, the synergistic effect of MoS2 and CoS2 is conducive to electron transfer, making the MoS2@CoS2 heterojunction show excellent electrocatalytic performance. The synergistic effects arising from the heterojunction and sulfur vacancy not only contribute to the observed catalytic prowess but also provide a valuable model and reference for the exploration of other efficient electrocatalysts. This research marks a significant stride toward overcoming the challenges associated with developing electrocatalysts for practical hydrogen evolution applications.

Dihydroartemisinin-driven TOM70 inhibition leads to mitochondrial destabilization to induce pyroptosis against lung cancer.

Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in-depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer. The affinity of DHA and TOM70 was analyzed by microscale thermophoresis (MST), pronase stability, and thermal stability. The functions and underlying mechanism were investigated using western blots, qRT-PCR, flow cytometry, and rescue experiments. TOM70 inhibition resulted in mtDNA damage and translocation to the cytoplasm from mitochondria due to the disruption of mitochondrial homeostasis. Further ex and in vivo findings also showed that the cGAS/STING/NLRP3 signaling pathway was activated by mtDNA and thereby malignant cells underwent pyroptosis, leading to enhanced immunogenicity of lung cancer cells in the presence of DHA. Nevertheless, DHA-induced mtDNA translocation and cGAS/STING/NLRP3 mobilization were synchronously attenuated when TOM70 was replenished. Finally, DHA was demonstrated to possess potent anti-lung cancer efficacy in vitro and in vivo. Taken together, these data confirm that TOM70 is an important target for DHA to disturb mitochondria homeostasis, which further activates STING and arouses pyroptosis to strengthen immunogenicity against lung cancer thereupon. The present study provides vital clues for phytomedicine-mediated anti-tumor therapy.

A multi-parametric prognostic model based on clinicopathologic features: vessels encapsulating tumor clusters and hepatic plates predict overall survival in hepatocellular carcinoma patients.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) is a newly described vascular pattern that is distinct from microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Despite its importance, the current pathological diagnosis report does not include information on VETC and hepatic plates (HP). We aimed to evaluate the prognostic value of integrating VETC and HP (VETC-HP model) in the assessment of HCC. METHODS: A total of 1255 HCC patients who underwent radical surgery were classified into training (879 patients) and validation (376 patients) cohorts. Additionally, 37 patients treated with lenvatinib were studied, included 31 patients in high-risk group and 6 patients in low-risk group. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to establish a prognostic model for the training set. Harrell's concordance index (C-index), time-dependent receiver operating characteristics curve (tdROC), and decision curve analysis were utilized to evaluate our model's performance by comparing it to traditional tumor node metastasis (TNM) staging for individualized prognosis. RESULTS: A prognostic model, VETC-HP model, based on risk scores for overall survival (OS) was established. The VETC-HP model demonstrated robust performance, with area under the curve (AUC) values of 0.832 and 0.780 for predicting 3- and 5-year OS in the training cohort, and 0.805 and 0.750 in the validation cohort, respectively. The model showed superior prediction accuracy and discrimination power compared to TNM staging, with C-index values of 0.753 and 0.672 for OS and disease-free survival (DFS) in the training cohort, and 0.728 and 0.615 in the validation cohort, respectively, compared to 0.626 and 0.573 for TNM staging in the training cohort, and 0.629 and 0.511 in the validation cohort. Thus, VETC-HP model had higher C-index than TNM stage system(p < 0.01).Furthermore, in the high-risk group, lenvatinib alone appeared to offer less clinical benefit but better disease-free survival time. CONCLUSIONS: The VETC-HP model enhances DFS and OS prediction in HCC compared to traditional TNM staging systems. This model enables personalized temporal survival estimation, potentially improving clinical decision-making in surveillance management and treatment strategies.

Structural equation modeling of dispositional mindfulness, internal environmental factors, external environmental factors, and self-care behaviors in people with type 2 diabetes.

BACKGROUND: To achieve suitable diabetes care, understanding the factors that affect self-care behaviors is necessary. OBJECTIVE: To construct a model of dispositional mindfulness, internal environmental factors, external environmental factors, and self-care behaviors in people with diabetes. DESIGN AND METHODS: This cross-sectional study analyzed a convenience sample of 311 people with type 2 diabetes in Taiwan. Data were collected through questionnaires, including the Diabetes Symptoms Checklist, Emotional Distress Scale, Empowerment Process Scale, Interpersonal Communication Scale and Self-Care Behavior scale. RESULTS: Structural equation modeling indicated that a model of dispositional mindfulness, internal environmental factors, external environmental factors, and self-care behaviors in the patients with diabetes best fit the data. Dispositional mindfulness (ß = 0.39), internal environmental factors (ß = 0.52), and external environmental factors (ß = 0.71) directly influenced self-care behaviors in the patients with diabetes. Dispositional mindfulness significantly indirectly affected self-care behaviors via internal and external environmental factors. CONCLUSIONS: To improve self-care behaviors, interventions should consider mindfulness training, and also include internal environmental factors and external environmental factors in the mindfulness training.

Recent advances in mesenchymal stem cell therapy for myocardial infarction.

Myocardial infarction refers to the ischemic necrosis of myocardium, characterized by a sharp reduction or interruption of blood flow in the coronary arteries due to the coronary artery occlusion, resulting in severe and prolonged ischemia in the corresponding myocardium and ultimately leading to ischemic necrosis of the myocardium. Given its high risk, it is considered as one of the most serious health threats today. In current clinical practice, multiple approaches have been explored to diminish myocardial oxygen consumption and alleviate symptoms, but notable success remains elusive. Accumulated clinical evidence has showed that the implantation of mesenchymal stem cell for treating myocardial infarction is both effective and safe. Nevertheless, there persists controversy and variability regarding the standardizing MSC transplantation protocols, optimizing dosage, and determining the most effective routes of administration. Addressing these remaining issues will pave the way of integration of MSCs as a feasible mainstream cardiac treatment.

Role of Ultrasound and Ultrasound-Based Prediction Model in Differentiating Follicular Thyroid Carcinoma From Follicular Thyroid Adenoma.

OBJECTIVES: This study aims to identify distinct ultrasound (US) characteristics for distinguishing follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA), and construct a user-friendly preoperative risk stratification model for thyroid follicular neoplasms. METHODS: In this retrospective study, patients diagnosed with pathologically confirmed FTA or FTC and undergoing US examinations between July 2017 and June 2021 were designated as the training cohort, and those from July 2021 to June 2023 were enrolled as the external validation set. We systematically assessed and compared the sonographic and clinical characteristics of FTC and FTA. Univariable and multivariable logistic regression analyses were used to assess the association of US features with FTC in the training set. A prediction nomogram model, incorporating US features independently associated with FTC, was developed and validated externally to assess its performance. RESULTS: A total of 645 patients (FTA/FTC = 530/115) were included in the training set, while 197 patients (FTA/FTC = 165/32) constituted the validation set. In the training set, solid composition, hypo-echogenicity, irregular margin, calcification, protrusion sign, trabecular formation, absent or thick halo, and mainly central hypervascularity were identified as independent factors associated with FTC. The prediction nomogram model constructed using these variables showed good performance in differentiating FTC from FTA with an area under the curve of 0.948 in the training set and 0.915 in the validation set. CONCLUSIONS: The preoperative nomogram model constructed based on US features serves as an effective tool for the risk stratification of thyroid follicular neoplasms.

Stigma and Stigma Resilience: Role of the Undergraduate and the Campus Environment.

RATIONALE: Stigma permeates disability experiences and compounds disability-related challenges. OBJECTIVE: Identify individual and environmental factors of stigmatizing experiences of college students with learning disabilities (LDs) and attention-deficit/hyperactivity disorder (ADHD). METHODOLOGY: A qualitative descriptive design was used with a thematic analysis of 30 transcripts from group discussions among four cohorts of undergraduates with LD/ADHD (N = 52). The Person-Environment-Occupation-Performance Model was used in interpreting the stigmatizing experiences. FINDINGS: The themes Perceived Misconceptions and Stigmatizing Actions describe key social-environmental factors. The theme Overcoming Stigmatizing Experiences elucidates key skills and processes for developing stigma resilience. These skills and processes were anchored in self-awareness and personally contextualized understanding of disability-related challenges and strengths, which were fostered during positive interactions with supportive others, such as instructors and mentors. IMPLICATIONS: Findings illustrate the biopsychosocial nature of stigma and highlight the role of individual and social-environmental factors in building stigma resilience among young adults with LD/ADHD.

Understanding Stigma and Resilience Among College Students with Learning Disabilities and ADHDWe studied how college students with learning disabilities (LDs) and attention-deficit/hyperactivity disorder (ADHD) experience stigma, which means feeling judged or treated unfairly because of their disabilities. We talked to 52 undergraduates in four groups to understand their experiences and found three main things related to stigma. First, students feel like others have wrong ideas about them and their disabilities. Second, they experience actions from others that make them feel stigmatized. Third, they develop ways to overcome these experiences. Students became more resilient to stigma when they understood themselves better and had support from others like teachers and mentors. Stigma is not just a personal thing for students with LD/ADHD; but it is also influenced by the people around them and how they see themselves.

Risk stratification in gastric cancer lung metastasis: Utilizing an overall survival nomogram and comparing it with previous staging.

BACKGROUND: Gastric cancer (GC) is prevalent and aggressive, especially when patients have distant lung metastases, which often places patients into advanced stages. By identifying prognostic variables for lung metastasis in GC patients, it may be possible to construct a good prediction model for both overall survival (OS) and the cumulative incidence prediction (CIP) plot of the tumour. AIM: To investigate the predictors of GC with lung metastasis (GCLM) to produce nomograms for OS and generate CIP by using cancer-specific survival (CSS) data. METHODS: Data from January 2000 to December 2020 involving 1652 patients with GCLM were obtained from the Surveillance, epidemiology, and end results program database. The major observational endpoint was OS; hence, patients were separated into training and validation groups. Correlation analysis determined various connections. Univariate and multivariate Cox analyses validated the independent predictive factors. Nomogram distinction and calibration were performed with the time-dependent area under the curve (AUC) and calibration curves. To evaluate the accuracy and clinical usefulness of the nomograms, decision curve analysis (DCA) was performed. The clinical utility of the novel prognostic model was compared to that of the 7th edition of the American Joint Committee on Cancer (AJCC) staging system by utilizing Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI). Finally, the OS prognostic model and Cox-AJCC risk stratification model modified for the AJCC system were compared. RESULTS: For the purpose of creating the OS nomogram, a CIP plot based on CSS was generated. Cox multivariate regression analysis identified eleven significant prognostic factors (P < 0.05) related to liver metastasis, bone metastasis, primary site, surgery, regional surgery, treatment sequence, chemotherapy, radiotherapy, positive lymph node count, N staging, and time from diagnosis to treatment. It was clear from the DCA (net benefit > 0), time-dependent ROC curve (training/validation set AUC > 0.7), and calibration curve (reliability slope closer to 45 degrees) results that the OS nomogram demonstrated a high level of predictive efficiency. The OS prediction model (New Model AUC = 0.83) also performed much better than the old Cox-AJCC model (AUC difference between the new model and the old model greater than 0) in terms of risk stratification (P < 0.0001) and verification using the IDI and NRI. CONCLUSION: The OS nomogram for GCLM successfully predicts 1- and 3-year OS. Moreover, this approach can help to appropriately classify patients into high-risk and low-risk groups, thereby guiding treatment.

Case report: A novel variant (H49N) in Myelin Protein Zero gene is responsible for a patient with Charcot-Marie-Tooth disease.

This report presents a case of Charcot-Marie-Tooth dominant intermediate D (CMTDID), a rare subtype of Charcot-Marie-Tooth disease, in a 52 years-old male patient. The patient exhibited mobility impairment, foot abnormalities (pes cavus), and calf muscle atrophy. Whole exome sequencing and Sanger sequencing suggested that a novel variant (NM_000530.8, c.145C>A/p.His49Asn) of MPZ may be the genetic lesion in the patient. The bioinformatic program predicted that the new variant (p.His49Asn), located at an evolutionarily conserved site of MPZ, was neutral. Our study expands the variant spectrum of MPZ and the number of identified CMTDID patients, contributing to a better understanding of the relationship between MPZ and CMTDID.

Pregnancy and the disease recurrence of patients previously treated for differentiated thyroid cancer: A systematic review and meta analysis.

BACKGROUND: Differentiated thyroid cancer (DTC) is commonly diagnosed in women of child-bearing age, but whether pregnancy influences the prognosis of DTC remains controversial. This study aimed to summarize existing evidence regarding the association of pregnancy with recurrence risk in patients previously treated for DTC. METHODS: We searched PubMed, Embase, Web of Science, Cochrane, and Scopus based on the prespecified protocol registered at PROSPERO (CRD42022367896). After study selection, two researchers independently extracted data from the included studies. For quantitative data synthesis, we used random-effects meta-analysis models to pool the proportion of recurrence (for pregnant women only) and odds ratio (OR; comparing the risk of recurrence between the pregnancy group and the nonpregnancy group), respectively. Then we conducted subgroup analyses to explore whether risk of recurrence differed by response to therapy status or duration of follow-up time. We also assessed quality of the included studies. RESULTS: A total of ten studies were included. The sample size ranged from 8 to 235, with participants' age at pregnancy or delivery ranging from 28 to 35 years. The follow-up time varied from 0.1 to 36.0 years. The pooled proportion of recurrence in all pregnant patients was 0.13 (95% confidence intervals [CI]: 0.06-0.25; I2 : 0.58). Among six included studies reporting response to therapy status before pregnancy, we observed a trend for increasingly higher risk of recurrence from excellent, indeterminate, and biochemically incomplete to structurally incomplete response to therapy ( Ptrend <0.05). The pooled risk of recurrence in the pregnancy group showed no evidence of a significant difference from that in the nonpregnancy group (OR: 0.75; 95% CI: 0.45-1.23; I2 : 0). The difference in follow-up time (below/above five years) was not associated with either the proportion of recurrence in all pregnant patients ( P >0.05) or the OR of recurrence in studies with a comparison group ( P >0.05). Two included studies that focused on patients with distant metastasis also did not show a significant difference in disease recurrence between pregnancy and nonpregnancy groups (OR: 0.51 [95% CI: 0.14-1.87; I2 : 59%]). CONCLUSION: In general, pregnancy appears to have a minimal association with the disease recurrence of DTC with initial treatment. Clinicians should pay more attention to progression of DTC among pregnant women with biochemical and/or structural persistence. REGISTRATION: PROSPERO, https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022367896.