Abemaciclib plus endocrine therapy versus chemotherapy after progression on prior palbociclib in HR+/HER2- metastatic breast cancer: A single center real-world study in China.

BACKGROUND: Cyclin-dependent kinase (CDK) 4/6 inhibitor plus endocrine therapy (ET) become standard-of-care for patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (MBC). However, the optimal therapeutic paradigm after progression on CDK4/6 inhibitor remains unclear. This study aimed to evaluate the efficacy and safety of abemaciclib with switching ET versus chemotherapy after progression on prior palbociclib-based ET in Chinese patients with HR+/HER2- MBC. METHODS: From 414 consecutive patients with HR+/HER2- MBC who had been treated with palbociclib plus ET from September 2018 to May 2022 in Peking University Cancer Hospital, we identified 80 patients who received abemaciclib plus switching ET or chemotherapy after progression on palbociclib, matched for age, original stage at diagnosis, disease-free interval, and tumor burden at 1:1 ratio. The primary endpoint was progression-free survival (PFS) compared using the Kaplan-Meier method. A Cox proportional hazard model was performed to identify clinical factors associated with PFS in the abemaciclib group. RESULTS: The median PFS was 6.0 months (95% confidence interval [CI]: 3.94-8.06) in abemaciclib group and 4.0 months (95% CI, 2.52-5.49) in chemotherapy group (p = 0.667). And, there was no difference in median PFS between the sequential and nonsequential arm (6.0 vs. 6.0 months) in the abemaciclib group though fewer lines of prior systemic therapy and longer PFS from prior palbociclib in the sequential arm. However, patients with prior palbociclib as the first-line therapy had a significantly longer median PFS versus prior palbociclib as ≥2nd-line therapy (11.0 vs. 5.0 months, p = 0.043). Based on multivariable analysis, ER+/PR+ was an independent factor associated with longer PFS. There was no significant difference in overall survival between the abemaciclib and chemotherapy groups (p = 0.069). CONCLUSION: Our findings indicate that abemaciclib plus switching ET might be one of feasible treatment options for Chinese patients with HR+/HER2- MBC after progression on prior palbociclib-based therapy in addition to chemotherapy.

Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study.

PURPOSE: This study evaluated the effectiveness of ovarian function suppression (OFS) of various gonadotropin-releasing hormone agonists (GnRHa) combined with aromatase inhibitors (AI) in premenopausal patients with hormone receptor-positive (HR-positive) breast cancer. Potential risk factors associated with insufficient OFS were analyzed. PATIENTS AND METHODS: Premenopausal HR-positive breast cancer patients who had received AI with GnRHa were studied retrospectively. Patients were divided into different groups according to monthly or trimonthly GnRHa schedules they received, and the effectiveness of OFS was compared between groups. Insufficient OFS was defined as at least one instance of estradiol ≥ 30 pg/ml. Patient data was gathered from medical records for this comparison. RESULTS: Of the 264 patients enrolled in this study, 117 were administered 3.6 mg of goserelin monthly (goserelin 1 M group), 63 received 3.75 mg of leuprorelin monthly (leuprorelin 1 M group) and 84 were given 11.25 mg of leuprorelin every three months (leuprorelin 3 M group). Overall, 7.20% experienced insufficient OFS. The incidence rates in the three GnRHa depot groups were 7.69%, 6.35%, and 7.14%, respectively, without a significant statistical difference (P = 0.900). Notably, younger patients exhibited a higher likelihood of insufficient OFS [OR = 0.900, 95%CI (0.824-0.982), P = 0.018]. CONCLUSION: Insufficient OFS remains a concern during GnRHa and AI treatment. The effectiveness of the three GnRHa depots commonly used in China seems comparable. Younger patients face a heightened risk of insufficient OFS.

De novo variation in ARID1B gene causes Coffin-Siris syndrome 1 in a Chinese family with excessive early-onset high myopia.

Coffin-Siris syndrome (CSS) is a rare autosomal dominant inheritance disorder characterized by distinctive facial features, hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degree, hypotonia, hirsutism/hypertrichosis, sparse scalp hair and varying kind of congenital anomalies. CSS can easily be misdiagnosed as other syndromes or disorders with a similar clinical picture because of their genetic and phenotypic heterogeneity. We describde the genotype-phenotype correlation of one patient from a healthy Chinese family with a novel genotype underlying CSS, who was first diagnosed in the ophthalmology department as early-onset high myopia (eoHM). Comprehensive ophthalmic tests as well as other systemic examinations were performed on participants to confirm the phenotype. The genotype was identified using whole exome sequencing, and further verified the results among other family members by Sanger sequencing. Real-time quantitative PCR (RT-qPCR) technology was used to detect the relative mRNA expression levels of candidate genes between proband and normal family members. The pathogenicity of the identified variant was determined by The American College of Medical Genetics and Genomics (ACMG) guidelines. STRING protein-protein interactions (PPIs) network analysis was used to detect the interaction of candidate gene-related proteins with high myopia gene-related proteins. The patient had excessive eoHM, cone-rod dystrophy, coarse face, excessive hair growth on the face, sparse scalp hair, developmental delay, intellectual disability, moderate hearing loss, dental hypoplasia, patent foramen ovale, chronic non-atrophic gastritis, bilateral renal cysts, cisterna magna, and emotional outbursts with aggression. The genetic assessment revealed that the patient carries a de novo heterozygous frameshift insertion variant in the ARID1B c.3981dup (p.Glu1328ArgfsTer5), which are strongly associated with the typical clinical features of CSS patients. The test results of RT-qPCR showed that mRNA expression of the ARID1B gene in the proband was approximately 30% lower than that of the normal control in the family, suggesting that the variant had an impact on the gene function at the level of mRNA expression. The variant was pathogenic as assessed by ACMG guidelines. Analysis of protein interactions in the STRING online database revealed that the ARID1A protein interacts with the high myopia gene-related proteins FGFR3, ASXL1, ERBB3, and SOX4, whereas the ARID1A protein antagonizes the ARID1B protein. Therefore, in this paper, we are the first to report a de novo heterozygous frameshift insertion variant in the ARID1B gene causing CSS with excessive eoHM. Our study extends the genotypic and phenotypic spectrums for ARID1B-CSS and supplies evidence of significant association of eoHM with variant in ARID1B gene. As CSS has high genetic and phenotypic heterogeneity, our findings highlight the importance of molecular genetic testing and an interdisciplinary clinical diagnostic workup to avoid misdiagnosis as some disorders with similar manifestations of CSS.

CDK7 in breast cancer: mechanisms of action and therapeutic potential.

Cyclin-dependent kinase 7 (CDK7) serves as a pivotal regulator in orchestrating cellular cycle dynamics and gene transcriptional activity. Elevated expression levels of CDK7 have been ubiquitously documented across a spectrum of malignancies and have been concomitantly correlated with adverse clinical outcomes. This review delineates the biological roles of CDK7 and explicates the molecular pathways through which CDK7 exacerbates the oncogenic progression of breast cancer. Furthermore, we synthesize the extant literature to provide a comprehensive overview of the advancement of CDK7-specific small-molecule inhibitors, encapsulating both preclinical and clinical findings in breast cancer contexts. The accumulated evidence substantiates the conceptualization of CDK7 as a propitious therapeutic target in breast cancer management.

Computational Interpersonal Communication Model for Screening Autistic Toddlers: A Case Study of Response-to-Name.

Interpersonal communication facilitates symptom measures of autistic sociability to enhance clinical decision-making in identifying children with autism spectrum disorder (ASD). Traditional methods are carried out by clinical practitioners with assessment scales, which are subjective to quantify. Recent studies employ engineering technologies to analyze children's behaviors with quantitative indicators, but these methods only generate specific rule-driven indicators that are not adaptable to diverse interaction scenarios. To tackle this issue, we propose a Computational Interpersonal Communication Model (CICM) based on psychological theory to represent dyadic interpersonal communication as a stochastic process, providing a scenario-independent theoretical framework for evaluating autistic sociability. We apply CICM to the response-to-name (RTN) with 48 subjects, including 30 toddlers with ASD and 18 typically developing (TD), and design a joint state transition matrix as quantitative indicators. Paired with machine learning, our proposed CICM-driven indicators achieve consistencies of 98.44% and 83.33% with RTN expert ratings and ASD diagnosis, respectively. Beyond outstanding screening results, we also reveal the interpretability between CICM-driven indicators and expert ratings based on statistical analysis.

Modulation of autophagy affected tumorigenesis induced by the envelope glycoprotein of JSRV.

Ovine pulmonary adenocarcinoma (OPA), caused by the jaagsiekte sheep retrovirus (JSRV), is a chronic, progressive, and contagious lung tumor that seriously affects sheep production. It also represents a valuable animal model for several human lung adenocarcinomas. However, little is known about the role of autophagy in OPA tumorigenesis. Here, Western blotting combined with transmission electron microscopy examination and Cyto-ID dye staining was employed for evaluation of changes of autophagic levels. The results of the present study showed that expression of the autophagy marker proteins Beclin-1 and LC3 was decreased in OPA lung tissues, as well as in cells overexpressing the envelope glycoprotein of JSRV (JSRV Env). Reduced numbers of autophagosomes were also observed in cells overexpressing JSRV Env, although assessment of autophagic flux showed that JSRV Env overexpression did not block the formation of autophagosomes, suggesting increased degradation of autolysosomes. Last, mouse xenograft experiments indicated that inhibition of autophagy by 3-methyladenine suppressed both tumor growth and the epithelial-to-mesenchymal transition. In conclusion, JSRV, through JSRV Env, takes advantage of the autophagy process, leading to the development of OPA.

Persistence of peripheral CD8 + CD28- T cells indicates a favourable outcome and tumour immunity in first-line HER2-positive metastatic breast cancer.

BACKGROUND: The contradictory role of CD8 + CD28- T cells in tumour immunity has been reported, while their biological and clinical significance in HER2-positive metastatic breast cancer (MBC) is still unknown. METHODS: HER2-positive MBC patients with no prior therapy in the metastatic setting were retrospectively recruited at two medical centres. Peripheral CD8 + CD28- T cells (pTCD8+CD28-) were detected at baseline and following therapeutic intervals. Progression-free survival (PFS) was compared according to pTCD8+CD28- levels. The molecular features of pTCD8+CD28- and its correlation with tumour immunity were also investigated. RESULTS: A total of 252 patients were enrolled, and the median follow-up time was 29.6 months. pTCD8+CD28- high at baseline has prolonged PFS compared to pTCD8+CD28- low (P = 0.001). Patients who maintained pTCD8+CD28- high had a longer PFS than those who kept pTCD8+CD28- low (P < 0.001). The enhanced pTCD8+CD28- level also indicates a longer PFS compared to pTCD8+CD28- low (P = 0.025). Here, pTCD8+CD28- was demonstrated as an antigen-experienced effector T cell. Higher IL-2 level (P = 0.034) and lower TGF-ß level (P = 0.016) in the serum and highly infiltrated CD8 + CD28- T cells (P = 0.037) were also connected to pTCD8+CD28- high. CONCLUSIONS: High pTCD8+CD28- level is associated with a favourable tumour immunity and a better PFS of HER2-targeting therapy in MBC patients.

The mediating role of psychological capital on the relationship between authentic leadership and innovative behaviour among Chinese nurses.

AIM: To explore the mediating role of psychological capital between authentic leadership and innovative behaviour among Chinese nurses. DESIGN: A cross-sectional study. METHODS: In December 2021, online surveys were delivered among nurses from 37 hospitals in Anhui Province by convenience sampling approach. The data was collected using the Chinese version of the Authentic Leadership Questionnaire, Nurse Psychological Capital Questionnaire and Nurse Innovative Behaviour Scale. The structural equation model and bootstrap test examined the mediating role of psychological capital between authentic leadership and innovative behaviour. RESULTS: 3495 Chinese nurses from 37 Anhui Province hospitals participated in this study. The mean item score of authentic leadership was 3.25 (SD 0.83), psychological capital was 4.85 (SD 0.89), and innovative behaviour was 2.82 (SD 0.84). Authentic leadership perceived by nurses, psychological capital, and innovative behaviour were statistically significant and positively correlated with each other (r = 0.524 ~ 0.806, p < 0.01). Psychological capital significantly mediated the association between authentic leadership and innovative behaviour (ß = 0.449, p < 0.001), and its mediating effect accounted for 76.75% of the total effect. CONCLUSION: Results suggest the importance of developing nurse managers' authentic leadership to foster nurses' psychological capital and innovation behaviour.

Potential Global Distribution of Paracoccus marginatus, under Climate Change Conditions, Using MaxEnt.

The papaya mealybug, Paracoccus marginatus, is an invasive pest species found all over the world. It is native to Mexico and Central America, but is now present in more than 50 countries and regions, seriously threatening the economic viability of the agricultural and forestry industry. In the current study, the global potential distribution of P. marginatus was predicted under current and future climatic conditions using MaxEnt. The results of the model assessment indicated that the area under the curve of the receiver operating characteristic ( ROC-AUC) was 0.949, while the TSS value was 0.820. The results also showed that the three variables with the greatest impact on the model were min temperature of coldest month (bio6), precipitation of wettest month (bio13), and precipitation of coldest quarter (bio19), with corresponding contributions of 46.8%, 31.1%, and 13.1%, respectively. The results indicated that the highly suitable areas were mainly located in tropical and subtropical regions, including South America, southern North America, Central America, Central Africa, Australia, the Indian subcontinent, and Southeast Asia. Under four climate scenarios in the 2050s and 2070s, the area of suitability will change very little. Moreover, the results showed that the area of suitable areas in 2070s increased under all four climate scenarios compared to the current climate. In contrast, the area of suitable habitat increases from the current to the 2050s under the SSP370 and SSP585 climate scenarios. The current study could provide a reference framework for the future control and management of papaya mealybug and other invasive species.

The insightful water quality analysis and predictive model establishment via machine learning in dual-source drinking water distribution system.

Dual-source drinking water distribution systems (DWDS) over single-source water supply systems are becoming more practical in providing water for megacities. However, the more complex water supply problems are also generated, especially at the hydraulic junction. Herein, we have sampled for a one-year and analyzed the water quality at the hydraulic junction of a dual-source DWDS. The results show that visible changes in drinking water quality, including turbidity, pH, UV254, DOC, residual chlorine, and trihalomethanes (TMHs), are observed at the sample point between 10 and 12 km to one drinking water plant. The average concentration of residual chlorine decreases from 0.74 ± 0.05 mg/L to 0.31 ± 0.11 mg/L during the water supplied from 0 to 10 km and then increases to 0.75 ± 0.05 mg/L at the end of 22 km. Whereas the THMs shows an opposite trend, the concentration reaches to a peak level at hydraulic junction area (10-12 km). According to parallel factor (PARAFAC) and high-performance size-exclusion chromatography (HPSEC) analysis, organic matters vary significantly during water distribution, and tryptophan-like substances and amino acids are closely related to the level of THMs. The hydraulic junction area is confirmed to be located at 10-12 km based on the water quality variation. Furthermore, data-driven models are established by machine learning (ML) with test R2 higher than 0.8 for THMs prediction. And the SHAP analysis explains the model results and identifies the positive (water temperature and water supply distance) and negative (residual chlorine and pH) key factors influencing the THMs formation. This study conducts a deep understanding of water quality at the hydraulic junction areas and establishes predictive models for THMs formation in dual-sources DWDS.

Endocrine therapy plus HER2-targeted therapy, another favorable option for HR+/HER2+ advanced breast cancer patients.

Advanced breast cancer (ABC) that is positive for hormone receptors (HRs) and human epidermal growth factor receptor 2 (HER2) is a cancer subtype with distinctive characteristics. The primary treatment guidelines suggest that a combination therapy comprising anti-HER2 therapy and chemotherapy should be administered as the initial treatment for HR-positive/ HER2-positive (HR+/HER2+) ABC. However, crosstalk between the HR and HER2 pathways can partially account for the resistance of HR+/HER2+ disease to HER2-targeted therapy. This, in turn, provides a rationale for the concomitant administration of HER2-targeted therapy and endocrine therapy (ET). Many clinical studies have confirmed that the combination of HER2-targeted therapy and ET as a first-line treatment is not inferior to the combination of HER2-targeted therapy and chemotherapy, and support its use as a first-line treatment choice for HR+/HER2+ ABC. Other drugs, such as antibody-drug conjugates, cyclin-dependent kinase 4/6 inhibitors, phosphatidylinositol 3-kinase-protein kinase B (AKT)-mammalian target of rapamycin inhibitors, and programmed cell death protein 1 or programmed cell death ligand 1 inhibitors, may also improve the prognosis of patients with breast cancer by blocking signaling pathways associated with tumor proliferation and break new ground for the treatment of HR+/HER2+ ABC.

Prevalence, early predictors, and outcomes of sepsis in neurocritical illnesses: A prospective cohort study.

BACKGROUND: Patients with neurocritically illness are an under-recognized population at high risk of sepsis. We aimed to investigate the prevalence, early predictors, and outcomes of sepsis in neuro-ICU. METHODS: Daily and accumulative incidences of sepsis in neuro-ICU were explored. Demographics, medical history, baseline disease severity scores, and baseline biomarkers regarding inflammation, immunology, organ function, and nutritional status were collected and analyzed as potential predictors of sepsis. Logistic regression analyses were used to determine the independent predictors, and a nomogram was used to estimate the individual probability of sepsis in neuro-ICU. RESULTS: 153 patients were included in this study. Fifty-nine (38.6%) patients developed sepsis, and 21 (14%) patients developed septic shock. More than 86% of the septic cases occurred within the first week. Sequential organ failure assessment score ((relative risk) RR 1.334, P = .026), history of diabetes (RR 2.346, P = .049), and transferrin (RR 0.128, P = .042) on admission are independent predictors of sepsis. Septic patients had significantly higher mortality (P = .011), higher medical cost (P = .028), and a lower rate of functional independence (P = .010), compared to patients without sepsis. CONCLUSIONS: Sepsis afflicted more than one-third of neurocritically-ill patients and occurred mostly in the first week of admission. History of diabetes, serum transferrin, and sequential organ failure assessment score on admission were early predictors. Sepsis led to significantly worse outcomes and higher medical costs.

Clinical impact and in vitro characterization of ADNP variants in pediatric patients.

BACKGROUND: Helsmoortel-Van der Aa syndrome (HVDAS) is a rare genetic disorder caused by variants in the activity-dependent neuroprotector homeobox (ADNP) gene; hence, it is also called ADNP syndrome. ADNP is a multitasking protein with the function as a transcription factor, playing a critical role in brain development. Furthermore, ADNP variants have been identified as one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability. METHODS: We assembled a cohort of 15 Chinese pediatric patients, identified 13 variants in the coding region of ADNP gene, and evaluated their clinical phenotypes. Additionally, we constructed the corresponding ADNP variants and performed western blotting and immunofluorescence analysis to examine their protein expression and subcellular localization in human HEK293T and SH-SY5Y cells. RESULTS: Our study conducted a thorough characterization of the clinical manifestations in 15 children with ADNP variants, and revealed a broad spectrum of symptoms including global developmental delay, intellectual disability, ASD, facial abnormalities, and other features. In vitro studies were carried out to check the expression of ADNP with identified variants. Two cases presented missense variants, while the remainder exhibited nonsense or frameshift variants, leading to truncated mutants in in vitro overexpression systems. Both overexpressed wildtype ADNP and all the different mutants were found to be confined to the nuclei in HEK293T cells; however, the distinctive pattern of nuclear bodies formed by the wildtype ADNP was either partially or entirely disrupted by the mutant proteins. Moreover, two variants of p.Y719* on the nuclear localization signal (NLS) of ADNP disrupted the nuclear expression pattern, predominantly manifesting in the cytoplasm in SH-SY5Y cells. LIMITATIONS: Our study was limited by a relatively small sample size and the absence of a longitudinal framework to monitor the progression of patient conditions over time. Additionally, we lacked in vivo evidence to further indicate the causal implications of the identified ADNP variants. CONCLUSIONS: Our study reported the first cohort of HVDAS patients in the Chinese population and provided systematic clinical presentations and laboratory examinations. Furthermore, we identified multiple genetic variants and validated them in vitro. Our findings offered valuable insights into the diverse genetic variants associated with HVDAS.

Real-world study of palbociclib combined with endocrine therapy for patients with metastatic breast cancer: A comparison of subsequent treatment patterns and HER2 expression analysis.

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy (ET) comprise the standard treatment for patients with hormone receptor-positive and human epidermal growth factor 2 (HER2)-negative metastatic breast cancer. The optimal systematic treatment after progression on palbociclib and the role of HER2 expression among these patients remain unclear. METHODS: The authors retrospectively identified 361 patients who received palbociclib combined with ET. Progression-free survival (PFS) and overall survival (OS) were analyzed based on subsequent treatments and HER2 status (PFSsub and OSsub, respectively). PFS1 and OS1 were calculated from palbociclib administration to disease progression/death and death from any cause, respectively. PFSsub and OSsub were calculated from subsequent treatment initiation. RESULTS: The median PFS1 and OS1 were 10.2 and 39.9 months, respectively. The median PFSsub and OSsub of 111 patients (54.7%) who received chemotherapy were 4.9 months and 20.0 months, respectively, whereas those of 89 patients (43.8%) who received endocrine backbone therapy were 5.9 months and 29.3 months, respectively. Among them, 31 patients (15.3%) who received abemaciclib combined with new ET showed better PFSsub and OSsub (12.2 months and not reached, respectively). The median PFS1 was significantly shorter in the HER2-low subgroup than in the HER2-zero subgroup among patients who received second-line or later palbociclib (6.1 vs. 7.8 months; p = .040) but did not differ among patients who received first-line palbociclib. CONCLUSIONS: Various regimens after palbociclib use were received. An improvement was noted in PFS among patients who received endocrine backbone therapy relative to chemotherapy, which may have been secondary to the receipt of chemotherapy by patients with more aggressive disease. HER2 status was not related to the effect of first-line palbociclib, but it may play a role in later lines.

Association of plant-based diets with total and cause-specific mortality across socioeconomic deprivation level: a large prospective cohort.

PURPOSE: Current evidence on the association between plant-based diet indices (PDIs) and mortality is inconsistent. We aimed to investigate the association of PDIs with all-cause and cause-specific mortality and to examine whether such associations were modified by socioeconomic deprivation level. METHODS: A total of 189,003 UK Biobank participants with at least one 24-h dietary assessment were included. All food items were categorised into three groups, including healthy plant foods, less healthy plant foods, and animal foods. Three PDIs, including the overall PDI (positive scores for all plant-based food intake and inverse scores for animal-based foods), the healthful PDI (hPDI) (positive scores only for healthy plant food intake and inverse scores for others), and the unhealthful PDI (uPDI) (positive scores only for less healthy plant food intake and inverse scores for others), were calculated according to the quantities of each food subgroup in three categories. The Townsend deprivation index was used as the indicator of socioeconomic deprivation level. Cox proportional hazard models were used to estimate the hazard ratios (HRs) of PDIs for all-cause and cause-specific mortality. The modification effects of socioeconomic deprivation levels on these associations were evaluated. RESULTS: During a median follow-up of 9.6 years, 9335 deaths were documented. Compared with the lowest quintile, the highest quintile of overall PDI was associated with adjusted HRs of 0.87 (95% CI 0.81-0.93) for all-cause mortality and 0.77 (0.66-0.91) for cardiovascular mortality. Compared with the lowest quintile, the highest quintile of hPDI was associated with lower risks of all-cause mortality (0.92, 0.86-0.98), and death caused by respiratory disease (0.63, 0.47-0.86), neurological disease (0.65, 0.48-0.88), and cancer (0.90, 0.82-0.99). Compared with the lowest quintile, the highest quintile of uPDI was associated with an HR of 1.29 (1.20-1.38) for all-cause mortality, 1.95 (1.40-2.73) for neurological mortality, 1.54 (1.13-2.09) for respiratory mortality, and 1.16 (1.06-1.27) for cancer mortality. The magnitudes of associations of hPDI and uPDI with mortality were larger in the most socioeconomically deprived participants (the highest tertile) than in the less deprived ones (p-values for interaction were 0.039 and 0.001, respectively). CONCLUSIONS: This study showed that having a high overall PDI and hPDI were related to a reduced risk of death, while the uPDI was linked to a higher risk of death. Sticking to a healthy plant-based diet may help decrease mortality risks across socioeconomic deprivation levels, especially for those who are the most socioeconomically deprived.

Variant allele frequency in circulating tumor DNA correlated with tumor disease burden and predicted outcomes in patients with advanced breast cancer.

PURPOSE: In patients with first-line advanced breast cancer (ABC), the correlation between ctDNA variant allele frequency (VAF) and tumor disease burden, and its prognostic value remains poorly investigated. METHODS: This study included patients with ABC diagnosed at Peking University Cancer Hospital who performed ctDNA test before receiving first-line treatment. Baseline plasma samples were collected for assessing ctDNA alterations and VAF with next-generation sequencing. The sum of tumor target lesion diameters (SLD) was measured with imaging methods according to RECIST 1.1 criteria. RESULTS: The final cohort included 184 patients. The median age of the cohort was 49.4 (IQR: 42.3-56.8) years. The median VAF was 15.6% (IQR: 5.4%-33.7%). VAF showed positive correlation with SLD in patients with relatively large tumor lesions (r = 0.314, p = 0.003), but not in patients with small tumor lesions (p = 0.226). VAF was associated with multiple metastasis sites (p = 0.001). Multivariate Cox regression analysis showed that high VAF was associated with shorter overall survival (OS) (HR: 3.519, 95% confidence interval (CI): 2.149-5.761), and first-line progression-free survival (PFS) (HR: 2.352, 95%CI: 1.462-3.782). Combined VAF and SLD improved prediction performance, both median OS and PFS of patients in VAF(H)/SLD(H) group were significantly longer than VAF(L)/SLD(L) group (mOS: 49.3 vs. 174.1 months; mPFS: 9.6 vs. 25.3 months). CONCLUSION: ctDNA VAF associated with tumor disease burden, and was a prognostic factor for patients with ABC. A combination of ctDNA test and radiographic imaging might enhance tumor burden evaluation, and improve prognosis stratification in patients with ABC.

Association between apolipoprotein B/A1 ratio and quantities of tissue prolapse on optical coherence tomography examination in patients with atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular disease (ASCVD) continues to be a major health concern globally. Apolipoprotein (Apo) B/A1 ratio is a reliable predictor of ASCVD and an important factor in assessing the risk of myocardial infarction. Tissue prolapse (TP) is defined as the tissue extrusion into the lumen through the stent struts after implantation, which is a significant factor for poor short-term outcomes such as acute and subacute thrombosis, severe myocardial necrosis, and vulnerable plaque. Therefore, the aim of this study was to investigate the relationship between Apo B/A1, plaque vulnerability, and tissue prolapse on optical coherence tomography (OCT). This study enrolled 199 patients with atherosclerotic cardiovascular disease (ASCVD) who underwent percutaneous coronary intervention (PCI). Both pre- and post-procedural optical coherence tomography (OCT) examinations were conducted to assess TP volume and plaque morphology. Logistic regression analyses were performed to identify potential risk factors for tissue prolapse volume. Receiver operator characteristic (ROC) curve analysis was carried out to evaluate the value of the Apo B/A1 ratio for tissue prolapse volume. The high Apo B/A1 ratio group showed a larger TP volume (P = 0.001) and a higher percentage of plaque rupture and erosion in comparison to the low Apo B/A1 ratio group (P = 0.022 and P = 0.008). The high Apo B/A1 ratio group and the high TP volume group also had a higher proportion of thin-cap fibroatheroma (TCFA) (P = 0.046, P = 0.021). Multivariate logistic regression analysis revealed that both Apo B/A1 ratio (odds ratio [OR]: 1.041, 95% confidence interval [CI] 1.007-1.076; P = 0.019) and TCFA (OR: 3.199, 95%CI 1.133-9.031; 0.028) were significantly related to high TP volume. Furthermore, the area under the curve (AUC) for predictive value of TP volume was 0.635 for Apo B/A1 (95% CI 0.554-0.717, P = 0.002) compared to 0.615 for low density lipoprotein cholesterol (LDL-C) (95% CI 0.533-0.697, P = 0.008). The Apo B/A1 ratio is an independent predictor of TP volume on OCT and is related to plaque vulnerability.

Association between consumption of sweeteners and endometrial cancer risk: a systematic review and meta-analysis of observational studies.

The purpose of this study is to further investigate the relationship between sweetener exposure and the risk of endometrial cancer (EC). Up until December 2022, a literature search in an electronic database was carried out utilizing PubMed, Web of Science, Ovid, and Scopus. The odds ratio (OR) and 95 % confidence interval (CI) were used to evaluate the results. Sweeteners were divided into nutritional sweeteners (generally refers to sugar, such as sucrose and glucose) and non-nutritional sweeteners (generally refers to artificial sweeteners, such saccharin and aspartame). Ten cohort studies and two case-control studies were eventually included. The study found that in 12 studies, compared with the non-exposed group, the incidence rate of EC in the sweetener exposed group was higher (OR = 1·15, 95 % CI = [1·07, 1·24]). Subgroup analysis showed that in 11 studies, the incidence rate of EC in the nutritional sweetener exposed group was higher than that in the non-exposed group (OR = 1·25, 95 % CI = [1·14, 1·38]). In 4 studies, there was no difference in the incidence rate of EC between individuals exposed to non-nutritional sweeteners and those who were not exposed to non-nutritional sweeteners (OR = 0·90, 95 % CI = [0·81, 1·01]). This study reported that the consumption of nutritional sweeteners may increase the risk of EC, whereas there was no significant relationship between the exposure of non-nutritional sweeteners and the incidence of EC. Based on the results of this study, it is recommended to reduce the intake of nutritional sweeteners, but it is uncertain whether use of on-nutritional sweeteners instead of nutritional sweetener.

Associations of sugar-sweetened, artificially sweetened, and naturally sweet juices with Alzheimer's disease: a prospective cohort study.

Epidemiological studies of sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) with Alzheimer's disease (AD) have provided controversial findings. Furthermore, little is known about the association between pure fruit/vegetable juices and AD. The present study aims to estimate the associations of SSBs, ASBs, and pure fruit/vegetable juices with AD, and to evaluate the theoretical effects of replacing SSBs and ASBs with the different consumption of pure fruit/vegetable juices on the risk of AD. This prospective cohort study of the UK Biobank included 206,606 participants aged 39-72 years free of dementia at baseline between 2006 and 2010. Dietary intake of SSBs, ASBs, and pure fruit/vegetable juices (naturally sweet juices) were collected using a 24-h dietary recall questionnaire completed between 2009 and 2012. Incident AD was identified by medical and mortality records. Cox proportional hazard models and substitution models were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 699 cases of AD were identified over a median follow-up of 9.5 years. The consumption of SSBs and ASBs (> 2 units/d) were associated with a higher risk of AD. However, participants who drank > 1-2 units/d of pure fruit/vegetable juices were associated with a lower risk of AD. In substitution models, replacing SSBs with an equivalent consumption of pure fruit/vegetable juices could be associated with a risk reduction of AD.

Long-term Outcome Analysis of Pyrotinib in Patients With HER2-Positive Metastatic Breast Cancer and Brain Metastasis: A Real-World Study.

BACKGROUND: Pyrotinib is currently approved for the treatment of HER2-positive advanced breast cancer in China. Data on the overall survival (OS) and efficacy in patients with brain metastasis (BM) remain scarce. This study evaluated the effectiveness of pyrotinib in a real-world setting, especially in patients with BM. METHODS: We reviewed patients with metastatic breast cancer treated with pyrotinib-based therapy between June 2018 and June 2022. Progression-free survival (PFS), OS, objective response rate, and safety were analyzed following the administration of pyrotinib. RESULTS: A total of 239 patients were included. The median PFS in patients who received pyrotinib-based therapy as first-line (15/239), second-line (115/239), or third-or-higher-line (109/239) treatment was 14.00, 9.33, and 8.20 months, respectively, and the median OS was not reached, 29.07 and 22.23 months, respectively. The median PFS in patients who pretreated with trastuzumab (214/239), trastuzumab plus pertuzumab (22/239), lapatinib (68/239), or trastuzumab emtansine (14/239) was 9.33, 6.87, 7.20, and 7.20 months, respectively. In 61 patients with BM, the median PFS was 7.50 months, the median central nervous system (CNS)-PFS was 11.17 months, and the median OS was 21.27 months. Furthermore, 19 patients with concomitant brain radiotherapy tended to achieve a longer OS than 42 patients without radiation (34.17 vs. 20.70 months, P = .112). CONCLUSIONS: Long-term outcomes of pyrotinib-based therapy are promising for patients with HER2-positive metastatic breast cancer in real world and in patients with BM, regardless of the treatment lines and prior anti-HER2 therapies.