Assessing the needs of patients with breast cancer and their families across various treatment phases using a Latent Dirichlet Allocation model: a text-mining approach to online health communities.

PURPOSE: This study aimed to assess the different needs of patients with breast cancer and their families in online health communities at different treatment phases using a Latent Dirichlet Allocation (LDA) model. METHODS: Using Python, breast cancer-related posts were collected from two online health communities: patient-to-patient and patient-to-doctor. After data cleaning, eligible posts were categorized based on the treatment phase. Subsequently, an LDA model identifying the distinct need-related topics for each phase of treatment, including data preprocessing and LDA topic modeling, was established. Additionally, the demographic and interactive features of the posts were manually analyzed. RESULTS: We collected 84,043 posts, of which 9504 posts were included after data cleaning. Early diagnosis and rehabilitation treatment phases had the highest and lowest number of posts, respectively. LDA identified 11 topics: three in the initial diagnosis phase and two in each of the remaining treatment phases. The topics included disease outcomes, diagnosis analysis, treatment information, and emotional support in the initial diagnosis phase; surgical options and outcomes, postoperative care, and treatment planning in the perioperative treatment phase; treatment options and costs, side effects management, and disease prognosis assessment in the non-operative treatment phase; diagnosis and treatment options, disease prognosis, and emotional support in the relapse and metastasis treatment phase; and follow-up and recurrence concerns, physical symptoms, and lifestyle adjustments in the rehabilitation treatment phase. CONCLUSION: The needs of patients with breast cancer and their families differ across various phases of cancer therapy. Therefore, specific information or emotional assistance should be tailored to each phase of treatment based on the unique needs of patients and their families.

Deciphering the prognostic features of bladder cancer through gemcitabine resistance and immune-related gene analysis and identifying potential small molecular drug PIK-75.

BACKGROUND: Bladder cancer (BCa) stands out as a prevalent and highly lethal malignancy worldwide. Chemoresistance significantly contributes to cancer recurrence and progression. Traditional Tumor Node Metastasis (TNM) stage and molecular subtypes often fail to promptly identify treatment preferences based on sensitivity. METHODS: In this study, we developed a prognostic signature for BCa with uni-Cox + LASSO + multi-Cox survival analysis in multiple independent cohorts. Six machine learning algorithms were adopted to screen out the hub gene, RAC3. IHC staining was used to validate the expression of RAC3 in BCa tumor tissue. RT-qPCR and Western blot were performed to detect and quantify the mRNA and protein levels of RAC3. CCK8, colony formation, wound healing, and flow cytometry analysis of apoptosis were employed to determine cell proliferation, migration, and apoptosis. Molecular docking was used to find small target drugs, PIK-75. 3D cell viability assay was applied to evaluate the ATP viability of bladder cancer organoids before and after PIK-75 treated. RESULTS: The established clinical prognostic model, GIRS, comprises 13 genes associated with gemcitabine resistance and immunology. This model has demonstrated robust predictive capabilities for survival outcomes across various independent public cohorts. Additionally, the GIRS signature shows significant correlations with responses to both immunotherapy and chemotherapy. Leveraging machine learning algorithms, the hub gene, RAC3, was identified, and potential upstream transcription factors were screened through database analysis. IHC results showed that RAC3 was higher expressed in GEM-resistant BCa patients. Employing molecular docking, the small molecule drug PIK-75, as binding to RAC3, was identified. Experiments on cell lines, organoids and animals validated the biological effects of PIK-75 in bladder cancer. CONCLUSIONS: The GIRS signature offers a valuable complement to the conventional anatomic TNM staging system and molecular subtype stratification in bladder cancer. The hub gene, RAC3, plays a crucial role in BCa and is significantly associated with resistance to gemcitabine. The small molecular drug, PIK-75 having the potential as a therapeutic agent in the context of gemcitabine-resistant and immune-related pathways.

Chemotherapy-related symptoms in children with leukemia: application of latent profile analysis and network analysis.

PURPOSE: Children with leukemia may experience a range of chemotherapy-related symptoms. Identifying subgroups and their distinct characteristics of symptoms may improve symptom management. We aimed to identify subgroups and their distinct characteristics of chemotherapy-related symptoms in children with leukemia. METHODS: A cross-sectional survey was conducted among 500 children with leukemia, who completed questionnaires that assessed their demographic and clinical characteristics, as well as the Memorial Symptom Assessment Scale. Latent profile analysis was conducted to identify subgroups of symptoms. Additionally, multiple regression analysis and network analysis were utilized to reveal the characteristics of each subgroup. RESULTS: Four subgroups were identified: "Profile 1: low symptom burden subgroup" (26.2%), "Profile 2: moderate symptom burden subgroup in transitional period" (14.8%), "Profile 3: moderate psychological symptom burden subgroup" (35.6%), and "Profile 4: high symptom burden subgroup" (23.4%). Multiple logistic regression analysis indicated that lower primary caregiver's education level, lower family monthly income, self-paid medical expenses, induction remission period, and consolidation enhancement period were associated with more severe symptoms of subgroups. Network analysis further revealed that nausea was the core symptom in Profiles 1 and 2, while the core symptom in Profile 3 was "I don't look like myself." Additionally, worrying was the core symptom in Profile 4. CONCLUSION: There exists heterogeneity in chemotherapy-related symptoms. Four subgroups and their corresponding characteristics of children with varying symptom severity were identified. Identifying these subgroups will facilitate personalized care, maximize intervention effectiveness, and alleviate symptom burden.

Retrospective Analysis of the Efficacy and Safety of Ultrasound-Guided Radiofrequency Ablation in the Treatment of Papillary Thyroid Microcarcinoma: A Follow-Up Study of Continuous Postoperative Surveillance and Large-Sample Data.

Objective: To retrospectively evaluate the efficacy and safety of ultrasound-guided radiofrequency ablation (RFA) in the treatment of papillary thyroid microcarcinoma (PTMC) through a follow-up study of continuous postoperative surveillance and large-sample data. Methods: The efficacy of ultrasound-guided RFA was evaluated by measuring the tumor volume reduction rate (VRR), tumor disappearance rate, and disease progression in 358 patients with low-risk unifocal PTMC who underwent ultrasound-guided RFA at Hangzhou Weja Hospital, while the safety was evaluated by measuring their complications. Results: The VRR was -745.69 ± 1012.69 (%), -150.35 ± 395.5 (%), 46.47 ± 138.74 (%), 92.95 ± 27.88 (%), 97.78 ± 10.99 (%), and 99.27 ± 3.82 (%), respectively, at 1, 3, 6, 12, 18, and 24 months after RFA. The corresponding tumor disappearance rate was 1.68%, 9.78%, 43.85%, 82.68%, 92.59%, and 95.63%, respectively. No local recurrence, new tumors, lymph node metastasis, distant metastasis, and deaths caused by recurrent/metastatic PTMC were found at the last follow-up. Except for 3 cases (0.84%) with thickening or hoarseness of voice and 3 cases (0.84%) with coughing during drinking water, no other complications were found. Conclusions: Ultrasound-guided RFA has good efficacy and safety for the treatment of low-risk unifocal PTMC and can be promoted for use in patients who meet the required indications.

Mutational landscape of head and neck cancer and cervical cancer in Chinese and Western population.

BACKGROUND: We aimed to unbiasedly map the genetic mutation profile of HNSC and CESC associated with HPV status in the Chinese population (SYSU-cohort) and compare them with Western population (TCGA-cohort). METHODS: Fifty-one HNSC patients (SYSU-HNSC) and 38 CESC patients (SYSU-CESC) were enrolled in this study. Genomic alterations were examined, and the profile was produced using the YuanSuTM450 gene panel (OrigiMed, Shanghai, China). The altered genes were inferred and compared to Western patients from TCGA cohorts. RESULTS: Compared to the TCGA-HNSC cohort, FGFR3 mutation was identified as a novel target in SYSU-HNSC with therapeutic potential. Compared to the TCGA-CESC cohort, some epigenetic regulation-associated genes were frequently mutated in SYSU-CESC cohort (KMT2C, KMT2D, KDM5C, KMT2A). CONCLUSION: In summary, our study provides unbiased insights into the genetic landscape of HNSC and CESC in the Chinese population and highlights potential novel therapeutic targets that may benefit Chinese patients.

Psychometric properties of the Chinese version of the PROMIS-Cancer-Anxiety item bank assessed using a graded response model.

Objective: This study aimed to examine the psychometric properties of the Chinese version of the Patient-Reported Outcome Measurement Information System (PROMIS)-Cancer-Anxiety item bank using a graded response model in a sample of patients with cancer. Methods: A cross-sectional study was conducted and the Chinese version of the PROMIS-Cancer-Anxiety item bank was used to measure anxiety in patients with cancer. The unidimensional structure of the item bank was evaluated using principal component analysis. Residual correlations and the graphs of item mean scores conditional on the rest scores were examined to evaluate the local independence and monotonicity of the items, respectively. Item characteristics were described using item parameter estimates and item information. Operating characteristic curves (OCCs) and test information curve (TIC) were also plotted. Measurement invariance across age, gender, and education level was assessed to identify possible differential item functioning (DIF). Results: A total of 1075 patients with cancer were enrolled. Under the assumptions of unidimensionality, local independence, and monotonicity, the discrimination parameters a ranged from 2.30 to 5.47, and the threshold parameters b ranged from b1 = -2.87 to b4 = 3.21 with proper intervals. Completely overlapped category curves were not observed among the OCCs of any items. Item information and TIC showed that the item bank had a wide measurement range. The DIFs for age, gender, and education level for all items were not remarkable. Conclusions: The results supported using the Chinese version of the PROMIS-Cancer-Anxiety item bank to measure anxiety and develop a computerized adaptive testing (CAT) system for anxiety in patients with cancer.

Risk factors for hyperactive delirium after laparoscopic radical gastrectomy under general anesthesia in patients with gastric cancer.

OBJECTIVE: This study aimed to analyze the risk factors for the occurrence of postoperative hyperactive delirium after laparoscopic radical gastrectomy under general anesthesia in patients with gastric cancer. METHODS: The clinical data of 280 gastric cancer patients who underwent laparoscopic radical gastrectomy under general anesthesia in First Affiliated Hospital of Gannan Medical University from January 2020 to June 2023 were retrospectively analyzed, and the types and incidence of postoperative delirium were recorded. The factors influencing the occurrence of postoperative hyperactive delirium were analyzed. RESULTS: Multi-factor logistic regression analysis showed that older age, high dosage of anesthetic drug consumption, high American Society of Anesthesiologists (ASA) classification (or ASA grade 3-4), long Post-anesthesia Care Unit (PACU) stay, and long extubation time were independent risk factors for the occurrence of hyperactive delirium after laparoscopic radical gastrectomy (OR > 1, P < 0.05). The area under the curve of the nomogram was used to predict the occurrence of hyperactive delirium after laparoscopic radical gastrectomy under general anesthesia was 0.903 (95% CI: 0.846-0.978). CONCLUSION: Older age, high dosage of anesthetic drug consumption, high ASA classification (or ASA grade 3-4), long PACU stay, and long extubation time were independent risk factors affecting the occurrence of hyperactive delirium after laparoscopic radical gastrectomy under general anesthesia.

Intratumoral CD103+ CD8+ T cells predict response to neoadjuvant chemoimmunotherapy in advanced head and neck squamous cell carcinoma.

BACKGROUND: Immune cell heterogenicity is known to determine the therapeutic response to cancer progression. Neoadjuvant chemoimmunotherapy (NACI) has shown clinical benefits in some patients with advanced head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism behind this clinical response is unknown. The efficacy of NACI needs to be potentiated by identifying accurate biomarkers to predict clinical responses. Here, we attempted to identify molecules predicting NACI response in advanced HNSCC. METHODS: We performed combined single-cell RNA sequencing (scRNA-seq) and multiplex immunofluorescence (mIHC) staining with tumor samples derived from NACI-treated HNSCC patients to identify a new tumor-infiltrating cell (TIL) subtype, CD103+ CD8+ TILs, associated with clinical response, while both in vitro and in vivo assays were carried out to determine its antitumor efficiency. The regulatory mechanism of the CD103+ CD8+ TILs population was examined by performing cell-cell interaction analysis of the scRNA-seq data and spatial analysis of the mIHC images. RESULTS: We established intratumoral CD103+ CD8+ TILs density as a determinant of NACI efficacy in cancers. Our scRNA-seq results indicated that the population of CD103+ CD8+ TILs was dramatically increased in the responders of NACI-treated HNSCC patients, while mIHC analysis confirmed the correlation between intratumoral CD103+ CD8+ TILs density and NACI efficacy in HNSCC patients. Further receiver operating characteristic curve analysis defined this TIL subset as a potent marker to predict patient response to NACI. Functional assays showed that CD103+ CD8+ TILs were tumor-reactive T cells, while programmed cell death protein-1 (PD-1) blockade enhanced CD103+ CD8+ TILs cytotoxicity against tumor growth in vivo. Mechanistically, targeting the triggering receptor expressed on myeloid cells 2-positive (TREM2+ ) macrophages might enhance the population of CD103+ CD8+ TILs and facilitate antitumor immunity during NACI treatment. CONCLUSIONS: Our study highlights the impact of intratumoral CD103+ CD8+ TILs density on NACI efficacy in different cancers, while the efforts to elevate its population warrant further clinical investigation.

Psychometric properties of the Chinese version of the functional assessment of chronic illness therapy-fatigue (FACIT-F) among patients with breast cancer.

BACKGROUND: Fatigue is the most frequent and distressing symptom affecting the physical, cognitive, and affective domains of breast cancer patients. The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) has been widely used in patients with chronic diseases and has shown satisfactory reliability and validity. This study aimed to examine the psychometric properties of the FACIT-F among Chinese patients with breast cancer. METHODS: Using a convenience sampling method, a cross-sectional survey (January 2020 and September 2022) was used with patients recruited from two tertiary hospitals in Shanghai, Mainland China, and a total of 597 patients completed a demographic information questionnaire, the FACIT-F and the Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B). Convergent validity was estimated by calculating the Pearson correlation coefficient of the FACIT-F with the FACT-B. Measurement invariance across age was performed by examining differential item functioning (DIF) across age groups (≤ 60 and > 60 years). The internal consistency and split-half reliability were performed for reliability analysis. Unidimensionality of the scale was evaluated by the principal component analysis by Rasch analysis. Additionally, Rasch analysis was performed for item difficulty levels, and an item-person map was used. RESULTS: No floor/ceiling effects were observed for the FACIT-F. Moderate correlations were found between FACIT-F and FACT-B (r = - 0.342, p < 0.01). Most items showed an absence of DIF regarding age, except for one item. In addition, the FACIT-F showed acceptable internal consistency. Principal component analysis of Rasch residuals showed that the proportion of variance explained by the FACIT-F was 53.3%, and the outfit mean square statistics for the items ranged from 0.68 to 1.90 and the infit MNSQ from 0.63 to 1.73. Additionally, an acceptable response between items and persons was found. CONCLUSIONS: The findings indicate that the Chinese version of the FACIT-F is a valid tool for the measurement of fatigue in breast cancer patients.

Septin 9 Orients the Apico-Basal Polarity Axis and Controls Plasticity Signals.

The cytoskeleton is a master organizer of the cellular cortex and membrane trafficking and therefore plays a crucial role in apico-basal polarity. Septins form a family of GTPases that assemble into non-polar filaments, which bind to membranes and recruit cytoskeletal elements such as microtubules and actin using their polybasic (PB) domains, to perform their broad biological functions. Nevertheless, the role of septins and the significance of their membrane-binding ability in apico-basal polarity remains under-investigated. Here, using 3D cultures, we demonstrated that septin 9 localizes to the basolateral membrane (BM). Its depletion induces an inverted polarity phenotype, decreasing ß-catenin at BM and increasing transforming growth factor (TGFß) and Epithelial-Mesenchymal Transition (EMT) markers. Similar effects were observed after deleting its two PB domains. The mutant became cytoplasmic and apical. The cysts with an inverted polarity phenotype displayed an invasive phenotype, with src and cortactin accumulating at the peripheral membrane. The inhibition of TGFß-receptor and RhoA rescued the polarized phenotype, although the cysts from overexpressed septin 9 overgrew and presented a filled lumen. Both phenotypes corresponded to tumor features. This suggests that septin 9 expression, along with its assembly through the two PB domains, is essential for establishing and maintaining apico-basal polarity against tumor development.

ClNAC100 Is a NAC Transcription Factor of Chinese Fir in Response to Phosphate Starvation.

Phosphate (Pi) deficiency is one of the most limiting factors for Chinese fir growth and production. Moreover, continuous cultivation of Chinese fir for multiple generations led to the reduction of soil nutrients, which hindered the yield of Chinese fir in southern China. Although NAC (NAM, ATAF, and CUC) transcription factors (TFs) play critical roles in plant development and abiotic stress resistance, it is still unclear how they regulate the response of Chinese fir to phosphate (Pi) starvation. Based on Pi-deficient transcriptome data of Chinses fir root, we identified a NAC transcription factor with increased expression under Pi deficiency, which was obtained by PCR and named ClNAC100. RT-qPCR confirmed that the expression of ClNAC100 in the root of Chinese fir was induced by phosphate deficiency and showed a dynamic change with time. It was positively regulated by ABA and negatively regulated by JA, and ClNAC100 was highly expressed in the roots and leaves of Chinese fir. Transcriptional activation assay confirmed that ClNAC100 was a transcriptional activator. The promoter of ClNAC100 was obtained by genome walking, which was predicted to contain a large number of stress, hormone, and growth-related cis-elements. Tobacco infection was used to verify the activity of the promoter, and the core promoter was located between -1519 bp and -589 bp. We identified 18 proteins bound to the ClNAC100 promoter and 5 ClNAC100 interacting proteins by yeast one-hybrid and yeast two-hybrid, respectively. We speculated that AHL and TIFY family transcription factors, calmodulin, and E3 ubiquitin ligase in these proteins might be important phosphorus-related proteins. These results provide a basis for the further study of the regulatory mechanism and pathways of ClNAC100 under Pi starvation.

Incidence and risk factors of intimate partner violence among patients with gynaecological cancer in China.

AIM: The aim of this study is to examine the incidence and risk factors for intimate partner violence (IPV) among patients with gynaecological cancer. DESIGN: A cross-sectional study design was employed. METHODS: Patients with gynaecological cancer were recruited from a tertiary hospital in Shandong, China. Eligible patients completed a survey including questions regarding their demographic and cancer-related characteristics, IPV experience and dyadic coping. RESULTS: A total of 429 patients were surveyed, 31% of them reported previous experiences with IPV, and negotiation was the most common type reported. The following variables were associated with IPV: a husband, wife and child/children family structure; a husband, wife, child/children and parent-in-law family structure; an annual household income ≥¥50,000 ($7207); and a similar or greater income earned by the patient than by her partner. PATIENT OR PUBLIC CONTRIBUTION: IPV in patients with gynaecological cancer is investigated in this study.

Cancer-related symptoms among young and middle-aged women undergoing chemotherapy for breast cancer: Application of latent class analysis and network analysis.

PURPOSE: To identify subgroups and symptom networks of cancer-related symptoms for women under 60 years who are undergoing chemotherapy for breast cancer. METHODS: A cross-sectional survey in Mainland China was conducted between August 2020 and November 2021. Participants completed questionnaires that collected demographic and clinical characteristics and featured the PROMIS-57 and the PROMIS-Cognitive Function Short Form. RESULTS: A total of 1033 participants were included in the analysis, and three-class model was identified: "severe symptom group" (17.6%; Class 1), "moderately severe anxiety, depression, and pain-interference group" (38.0%; Class 2), and "mild symptom group" (44.4%; Class 3). Patients who were in menopause (OR = 3.05, P < .001), undergoing a combination of medical treatments (OR = 2.39, P = .003), and who had experienced complications (OR = 1.86, P = .009) were more likely to belong to Class 1. However, having two or more children increased the likelihood of belonging to Class 2. Additionally, network analysis showed that severe fatigue level was the core symptom among the full sample. As for Class 1, feeling helpless and severe fatigue level were the core symptoms. Regarding Class 2, the impact of pain interfere on the ability to participate in social activities and feeling hopeless were found to be the targeted symptoms for intervention. CONCLUSION: Menopause, receiving a combination of medical treatments, and experiencing complications characterize the group with the most symptom disturbance. Moreover, different interventions should be performed for core symptoms in patients with varied symptom disturbances.

Identification of age differences in cancer-related symptoms in women undergoing chemotherapy for breast cancer in China.

BACKGROUND: Both contextual and cancer-related factors could be identified as causes of the interindividual variability observed for symptoms experienced during breast cancer treatment with chemotherapy. Understanding age differences and the predictors of latent class memberships for symptom heterogeneity could contribute to personalized interventions. This study aimed to identify the role of age differences on cancer-related symptoms in women undergoing chemotherapy for breast cancer in China. METHODS: A cross­sectional survey was conducted among patients with breast cancer in three tertiary hospitals in central China between August 2020 to December 2021. The outcomes of this study included sociodemographic and clinical characteristics, Patient-Reported Outcomes Measurement Information System (PROMIS)-57 and PROMIS-cognitive function short form scores. RESULTS: A total of 761 patients were included, with a mean age of 48.5 (SD = 11.8). Similar scores were observed across age groups for all symptoms except for fatigue and sleep disturbance domains. The most central symptoms varied among each group, and were fatigue, depression, and pain interference for the young-aged, middle-aged, and elderly-aged groups, respectively. In the young-aged group, patients without health insurance (OR = 0.30, P = 0.048) and in the fourth round of chemotherapy or above (OR = 0.33, P = 0.005) were more likely to belong to low symptom classes. In the middle-aged group, patients in menopause (OR = 3.58, P = 0.001) were more likely to belong to high symptom classes. In the elderly-aged group, patients with complications (OR = 7.40, P = 0.003) tended to belong to the high anxiety, depression, and pain interference classes. CONCLUSIONS: Findings from this study indicated that there is age-specific heterogeneity of symptoms present for Chinese women being treated for breast cancer with chemotherapy. Tailored intervention should consider the impact of age to reduce patients' symptom burdens.

Classification of symptom subtypes in patients with multiple myeloma during treatment: a cross-sectional survey study in China.

OBJECTIVES: To classify subgroups of cancer-related symptoms in patients with multiple myeloma (MM) during treatment and examine between-group differences in demographic and clinical characteristics in addition to functional status. DESIGN: Cross-sectional survey study. SETTING: Haematology department of two tertiary hospitals affiliated with Guilin Medical University in China. PARTICIPANTS: Using a convenience sampling method, questionnaires were distributed to patients with MM visiting two hospitals in Guilin, China. INTERVENTIONS: The patients were categorised into subgroups based on cancer-related symptoms using a latent class analysis. An analysis of covariance was performed to examine how demographic and clinical characteristics and functional status differed among the subgroups. RESULTS: In total, 216 patients completed the survey, with an average age of 60.3 years. A three-class solution was identified: low symptom burden group (class 1, 36.6%), moderate symptom burden group (class 2, 34.2%) and high symptom burden group (class 3, 29.2%). Patients with low monthly family income (OR=3.14, p=0.010) and complications of MM bone disease (OR=2.95, p=0.029) were more likely to belong to class 2. The predictors of high-burden symptoms were treated with painkillers, antidepressants or hypnotic drugs (OR=3.68, p=0.012) and <5000 daily step counts (OR=2.52, p=0.039) in class 3. Functional status was correlated with symptom burden, with patients in classes 3 and 1 reporting significantly higher and lower functional status, respectively (p<0.05). CONCLUSIONS: Patients with MM experienced varying degrees of symptoms during treatment. The identification of patients with high symptom burden management should focus on the assessment of demographic and clinical characteristics, in addition to functional status.

Detection and Characterization of In Vitro Payload-Containing Catabolites of Noncleavable Antibody-Drug Conjugates by High-Resolution Mass Spectrometry and Multiple Data Mining Tools.

The formation and accumulation of payload-containing catabolites (PCCs) from a noncleavable antibody-drug conjugate (ADC) in targeted and normal tissues are directly associated with the therapeutic effect and toxicity of the ADC, respectively. Understanding the PCC formation is important for supporting the payload design and facilitating preclinical evaluation of ADCs. However, detection and identification of PCCs of a noncleavable ADC are challenging due to their low concentrations and unknown structures. The main objective of this study was to develop and apply a generic liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method for profiling PCCs in vitro. Noncleavable ADCs, ado-trastuzumab emtansine (T-DM1) and ADC-1, were incubated in liver lysosomes, liver S9, and/or cancer cells followed by data acquisition using LC-HRMS. Profiling PCCs mainly relied on processing LC-HRMS datasets using untargeted precise and thorough background subtraction (PATBS) processing and targeted product ion filtering (PIF). As a result, 12 PCCs of T-DM1 were detected and structurally characterized in human liver lysosomal incubation, a majority of which consisted of 4-[N-maleimidomethyl]cyclohexane-1-carboxylate (MCC)-DM1 and a few amino acids. Additionally, the incubation of ADC-1 in human, rat, and monkey liver S9 and cancer cells generated one major and three very minor PCCs, verifying the payload design. The results demonstrate that PATBS enabled the comprehensive profiling of PCCs regardless of their molecular weights, charge states, and fragmentations. As a complementary tool, PIF detected specific PCCs with superior sensitivity. The combination of the in vitro metabolism systems and the LC-HRMS method is a useful approach to profiling in vitro PCCs of noncleavable ADCs in support of drug discovery programs. SIGNIFICANCE STATEMENT: Profiling in vitro payload-containing catabolites (PCCs) of a noncleavable antibody-drug conjugate (ADC) is important for optimization of the payload design and preclinical evaluation of ADC. However, currently used analytical approaches often fail to quickly provide reliable PCC profiling results. The work introduces a new liquid chromatography high resolution mass spectrometry method for comprehensive and rapid detection and characterization of PCCs released from a noncleavable ADC in liver lysosomes and S9 incubations.

Carbon dots-embedded amorphous nickel oxide for highly enhanced photocatalytic redox performance.

Amorphous materials reveal promising prospects in photocatalysis for the abundant active sites and tunable electronic configuration due to the lattice flexibility. However, the intrinsic lattice distortion could also cause the self-trapping effect and results in the recombination of photogenerated carriers. This disadvantage could be modified by the small size of amorphous domains for reducing charge migration distance. For this purpose, carbon dots (CDs) are introduced as the heterogeneous nucleus to regulate the configuration and composition of the amorphous nickel oxides for efficient utilization of photocarriers in catalytic reactions. The resultant nanocomposites a-NiOx/CDs show the densely distributed CDs embedded in the amorphous nickel oxide with dual valences of Ni2+ and Ni3+, and they reveal superior activities in photocatalytic oxidation and reduction compared with the single amorphous nickel oxide. The extraordinary photocatalytic performance is attributed to the synergetic function of their excellent separation efficiency of photoinduced charges and the cyclic conversion between Ni2+ and Ni3+ in the defects. This work provides inspiration for the modification and photocatalytic application of the amorphous materials.

Dyadic coping in young and middle-aged women with gynecological cancer: a latent class analysis.

PURPOSE: Cancer is a shared stress that can cause psychosocial and emotional burdens for both patients and their partners. This study aimed to identify patterns of dyadic coping (DC) among young and middle-aged women with gynecological cancer and to assess between-group differences. METHODS: Between June 2021 and November 2021, patients with gynecological cancer who received therapy in a tertiary-grade hospital in Shandong, China, completed questionnaires including a demographic questionnaire, the Dyadic Coping Inventory, the PROMIS-Anxiety Short Form, the PROMIS-Depression Short Form, and the revised Conflict Tactics Scale and were classified into subtypes by latent class analysis. RESULTS: The sample consisted of 339 patients. Approximately one-third of the patients, especially cervical cancer patients, were exposed to varying degrees of DC issues. Three patterns were identified: class 1, middle-DC group (33.6%); class 2, low-DC group (32.2%); and class 3, high-DC group (34.2%). Postmenopausal patients were more likely to be included in class 1, while patients with cervical cancer were more likely to be included in class 2 (p < 0.05). Additionally, patients in class 2 were more likely to report insufficient emotional support (p < 0.05). A positive correlation was found for social relationship domains, and a negative correlation was found for anxiety and depression (p < 0.05). CONCLUSION: The findings indicated a high prevalence of DC in young and middle-aged women with gynecological cancer. Overall, participants scored in the low-to-middle range in terms of DC levels, and patients with cervical cancer and those with insufficient emotional support were more likely to report DC issues and require additional attention.

Nomogram based on intramuscular adipose tissue content for predicting the prognosis of patients with gallbladder cancer after radical resection.

Background: To investigate the predictive value of intramuscular adipose tissue content (IMAC) on the outcome of gallbladder cancer (GBC) patients after resection, by then develop and evaluate a nomogram to predict the prognosis of GBC patients. Methods: This research incorporated 123 patients with a pathological diagnosis of GBC. Evaluating the prognosis by the Kaplan-Meier method. Independent predictors of overall survival (OS) were screened using multifactorial Cox regression analysis, and a nomogram was constructed from these. Consistency index and calibration curve were used to identify and calibrate the nomogram. The accuracy of the nomogram was assessed by receiver operating characteristic (ROC) curve and decision curve analysis (DCA) was used to assess the net benefit. Results: Patients with high IMAC showed a worse prognosis. A nomogram was constructed to predict OS based on IMAC. The C-index for the nomogram was 0.804. The calibration curve showed well performance of the nomogram. The area under the ROC curve (AUC) for the nomogram at three and five years was 0.839 and 0.785, respectively. A high net benefit was demonstrated by DCA. Conclusions: IMAC was a valid predictor for GBC patients. A nomogram with good performance is constructed to predict the prognosis of GBC patients.