Association Between Social Determinants of Health and Cancer Treatment Delay in an Urban Population.

PURPOSE: Delays in oncologic time to treatment initiation (TTI) independently and adversely affect disease-specific mortality. Social Determinants of Health (SDoH) are increasingly recognized as significant contributors to patients' disease management and health outcomes. Our academic center has validated a 10-item SDoH screener, and we elucidated which specific needs may be predictive of delayed TTI. METHODS: This is a retrospective cohort study at an urban academic center of patients with a SDoH screening and diagnosis of breast, colorectal, endocrine/neuroendocrine, GI, genitourinary, gynecologic, head and neck, hematologic, hepatobiliary, lung, or pancreatic cancer from 2018 to 2022. Variables of interest included household income, tumor stage, and emergency department (ED) or inpatient admission 30 days before diagnosis. Factors associated with delayed TTI ≥45 days were assessed using multivariable logistic regression. RESULTS: Among 2,328 patients (mean [standard deviation] age, 64.0 (12.8) years; 66.6% female), having >1 unmet social need was associated with delayed TTI (odds ratio [OR], 1.68; 95% CI, 1.54 to 1.82). The disparities most associated with delay were legal help, transportation, housing stability, and needing to provide care for others. Those with ED (OR, 0.49; 95% CI, 0.44 to 0.54) or inpatient (OR, 0.54; 95% CI, 0.50 to 0.58) admission 30 days before diagnosis were less likely to experience delay. CONCLUSION: Delays in oncologic TTI ≥45 days are independently associated with unmet social needs. ED or inpatient admissions before diagnosis increase care coordination, leading to improved TTI. Although limitations included the retrospective nature of the study and self-reporting bias, these findings more precisely identify targets for intervention that may more effectively decrease delay. Patients with SDoH barriers are at higher risk of treatment delay and could especially benefit from legal, transportation, caregiver, and housing assistance.

Pre- vs Post-Operative Levator Ani Subtended Volume in Patients Undergoing Hysterectomy: A Comparative Imaging Study.

INTRODUCTION AND HYPOTHESIS: The effects of hysterectomy on pelvic floor function remain uncertain, with the levator ani muscle (LAM) playing a critical role in pelvic support. The levator ani subtended volume (LASV) is an objective measure of the LAM's anatomical volume, derived from magnetic resonance imaging (MRI). This study was aimed at assessing the consistency between MRI and computed tomography (CT) in quantifying LASV, and to investigate the effect of hysterectomy on the LAM. METHODS: This retrospective study analyzed a cohort of 55 hysterectomy patients, utilizing pre-operative pelvic MRI and post-operative CT scans to measure the LASV. To evaluate the consistency between MRI and CT, the study employed the intraclass correlation coefficient and Bland-Altman agreement analysis in a subset of 32 patients with both pre-operative scans. A paired-samplet test was used to analyze LASV changes pre- and post-hysterectomy, and linear regression analysis was performed to account for potential risk factors that may influence post-operative LASV. RESULTS: High consistency between MRI and CT in measuring LASV was found, with an ICC of 0.911. We observed a significant increase in LASV following hysterectomy, with mean volume pre- and post-operatively of 16.66 cm3 and 18.87 cm3 respectively. Age and body mass index were significant predictors of post-hysterectomy LASV, whereas parity and the type of hysterectomy had no significant impact. CONCLUSIONS: Hysterectomy significantly affects the LAM, resulting in an increase in post-operative LASV. Moreover, this study verifies that MRI and CT can be used interchangeably for LASV measurements in clinical practice.

Association of tumor growth rate with overall survival and recurrence among patients with laryngeal squamous cell carcinoma.

BACKGROUND: Delay in time to treatment initiation (TTI) is associated with worsened survival outcomes in laryngeal squamous cell carcinoma (LSCC). It is unclear whether this is due to tumor growth or an increased risk of metastatic disease. METHODS: This retrospective cohort study at one academic center included patients with LSCC who underwent radiotherapy/chemoradiotherapy between 2005 and 2017. We examined the association between tumor growth rate (TGR) and survival outcomes. RESULTS: Among 105 patients (mean age, 63.8 ± 11.1 years; 72% male), the threshold between "slow-growing" and "fast-growing" tumors was >0.036 mL/day (survival) and >0.082 mL/day (recurrence). Faster growth was associated with worse overall survival (OS) (hazard ratio, 1.97; 95% confidence interval [CI], 0.94-4.13) and increased recurrence (odds ratio, 9.10; 95% CI, 2.40-34.4). CONCLUSIONS: TGR >0.036 mL/day during TTI was associated with decreased OS, and >0.082 mL/day was associated with increased recurrence. Tumor measurement in patients experiencing delay may identify those who could benefit from escalated therapy.

Development of an "on-off-on" fluoroprobe utilizing an anthrylimidazole-based fluorescent ionic liquid for sensitive Cr(VI) and ascorbic acid detection.

Developing a rapid detection method of Cr(VI) and ascorbic acid (AA) is vital in the food and environmental fields. Herein, an anthrylimidazole-based fluorescent ionic liquid (AI-FIL) with the advantageous fluorescent properties was successfully prepared and used to construct a promising "on-off-on" fluoroprobe for rapid/sensitive Cr(VI) and AA detection. Cr(VI) could effectively quench the fluorescence of AI-FIL owing to the inner-filter effect and photoinduced electron-transfer process. However, the decreased fluorescence could be rapidly recovered by AA owing to the redox reaction between AA and Cr(VI). For Cr(VI) detection, a satisfactorily linear response (0.03-300 µM) was achieved with the corresponding detection limit of 9 nM. For AA detection, a good linearity from 1 to 1000 µM was obtained with the resultant detection limit of 0.3 µM. Moreover, the AI-FIL based fluoroprobe was successfully utilized for Cr(VI) and AA detection in food and water samples with satisfactory accuracy and precision.

Sedimentary Paleoenvironment and Organic Matter Enrichment Characteristics of Lacustrine Shahezi Shale in Songliao Basin: Insights from the Continental Scientific Drilling.

The lacustrine shale of the Shahezi Formation in the Songliao Basin has obvious organic matter enrichment characteristics and great potential for oil and gas resources. At present, the understanding of the sedimentary paleoenvironment and organic matter enrichment characteristics of the lacustrine shale of the Shahezi Formation is relatively weak. Therefore, taking the international continental scientific drilling Program (ICDP) borehole Songke-2 (SK-2) with continuous and whole Shahezi cores as the research object, combined with organic geochemistry, elemental geochemistry, and logging data, the sedimentary paleoenvironment and organic matter enrichment mechanism were studied. The results show that the organic matter of Shahezi shale is generally in the high to over mature stage. The kerogen type of organic matter is mainly II2-III. The organic matter is mainly derived from the lake basin's own algae and terrestrial higher plants. The total organic carbon (TOC) content of Shahezi shale is relatively high, and the TOC is mainly distributed between 1% and 2%. The Shahezi Formation is dominated by clay shale and siliceous shale, and experienced moderate chemical weathering during deposition. According to the analysis of organic geochemistry and elemental geochemistry data, the paleoenvironment of organic matter deposition in Shahezi shale was dominated by warm and humid climate in the early stage, and then experienced multiple cooling and arid periods. The climate type turned to semihumid-semiarid, with stable terrigenous debris input, low deposition rate, brackish water salinity and oxygen-rich-oxygen-poor water environment. The sedimentary period of Shahezi Formation is in the Cretaceous oceanic anoxic Aptian-Albian stage. During the oceanic anoxic event, the anoxic sedimentary environment and the frequent volcanic activity have an important impact on the organic matter enrichment. The oceanic anoxic event and volcanic activity are the main causes of water body hypoxia in the lake basin. The nutrients brought by volcanic activity are also one of the reasons for promoting the growth of lake basin organisms, creating good conditions for organic matter enrichment. The enrichment of organic matter in Shahezi Formation is the result of the interaction and coupling of various factors such as paleoclimate, paleoenvironment, paleoproductivity, water environment, terrestrial input, and major geological events. And, the organic matter enrichment model of Shahezi Formation shale is established.

Recovery of rare earth elements from mine wastewater using alginate microspheres encapsulated with zeolitic imidazolate framework-8.

There is increasing demand and interest in efficient methods for the recovery of rare earth elements (REEs) from wastewater because of the growing concerns associated with the negative impacts of REEs-rich waste discharged on pristine ecosystems. Here, we designed a ZIF-8@ALG composite hydrogel by encapsulating zeolitic imidazolate frameworks-8 (ZIF-8) into sodium alginate and poly (vinyl alcohol) double cross-linked networks (ALG) for the recovery of REEs from mine wastewater. ZIF-8@ALG showed exceptional REEs adsorption performance with the most superior separation factor (Ho/Mn) of 597.5. For the REEs considered, the ZIF-8@ALG composite exhibited a preference for heavy REEs with high adsorption efficiencies (65.3 ∼ 97.2%) and distribution coefficients (2045.5 ∼ 28500.0 mL·g-1). Adsorption involved a combination of electrostatic attraction, complexation and ion exchange mechanisms. REEs adsorbed on ZIF-8@ALG could also be desorbed using sodium citrate via ion-exchange and complexation, thus achieving efficient REEs recovery. In addition, ZIF-8@ALG was stable and reusable, maintaining effective adsorption in wastewater over four consecutive cycles, where the optimal adsorption efficiency reached 80.0%. Overall, this study provided an effective and feasible method for the recovery of REEs in mine wastewater, and confirmed that ZIF-8-based materials have significant potential for REEs recovery applications in wastewater engineering treatment.

Effect of maternal vaccination on infant morbidity in Bangladesh.

BACKGROUND: Risk factors of infant mortality in Africa and south Asian countries have been broadly discussed. However, infant morbidity is largely underestimated. We analyzed the data from a randomized vaccine trial in Bangladesh to identify and assess the effect of risk factors on infant morbidity. METHODS: Pregnant women were randomly assigned to receive either inactivated influenza vaccine or pneumococcal polysaccharide vaccine and the infants were randomly assigned to receive 7-valent pneumococcal conjugate vaccine or Hib conjugate vaccine at week 6, 10 and 14. The data were collected from August 2004 through December 2005. Each pair of infant and mother were followed for 24 weeks after birth with weekly visits. Generalized estimating equations (GEE) for repeated measurements and Poisson regression models were used to identify the risk factors and evaluate their effect on the longitudinal incidence and total number of episodes of respiratory illness with fever (RIF), diarrhea disease, ear problem and pneumonia. RESULTS: A total of 340 pregnant women were randomized with mean age of 25 years. The baseline mother and infant characteristics were similar between two treatment groups. Exclusive breastfeeding and higher paternal education level were common factors associated with lower infant morbidity of RIF (adjusted OR = 0.40 and 0.94 with p < 0.01 and p = 0.02, respectively), diarrhea disease (adjusted OR = 0.39 and 0.95 with p < 0.01 and p = 0.04, respectively), and ear problem (adjusted OR = 0.20 and 0.76 with p < 0.01 and p < 0.01, respectively). Maternal influenza vaccine significantly reduced the incidence of RIF (adjusted OR = 0.54; p < 0.01) but not diarrhea disease or ear problem (p > 0.05). Female infants had lower incidence of diarrhea disease (adjusted OR = 0.67; p = 0.01) and ear problem (adjusted OR = 0.12; p = 0.01). CONCLUSIONS: Maternal influenza vaccination, exclusive breastfeeding, female children, and higher paternal education level significantly reduced the infant morbidity within the 24 weeks after birth in Bangladesh.

METTL16 deficiency attenuates apoptosis through translational control of extrinsic death receptor during nutrient deprivation.

METTL16 is a well-characterized m6A methyltransferase that has been reported to contribute to tumorigenesis in various types of cancer. However, the effect of METTL16 on tumor progression under restricted nutrient conditions, which commonly occur in tumor microenvironment, has yet to be elucidated. Herein, our study initially reported the inhibitory effect of METTL16 depletion on apoptosis under amino acid starvation conditions. Mechanistically, we determined that the METTL16 knockdown represses the expression of extrinsic death receptors at both transcription and translation levels. Depletion of METTL16 prevented protein synthesis of GCN2, resulting in diminished ATF4 expression in a GCN2-eIF2α-dependent manner. Reduction of ATF4 further declined the expression of apoptotic receptor protein DR5. Meanwhile, METTL16 deficiency directly hampered protein synthesis of FADD and DR5, thereby impairing apoptosis and promoting cancer cell survival. Taken together, our study provides novel evidence for the involvement of METTL16 in regulating cancer progression, suggesting that METTL16 as a potential therapeutic target for cancer treatment.

Immunotherapy Efficacy in Advanced Hepatocellular Carcinoma in a Diverse and Underserved Population in the United States.

Background :   Incidence of hepatocellular cancer (HCC) in the Bronx is 61% higher than the rest of New York State. Underserved populations are not well represented in clinical trials of immune checkpoint inhibitors (ICI). Methods: Demographics were tabulated for 194 patients treated with ICI at the Montefiore-Einstein Comprehensive Cancer Center (MECCC) between 2017 and 2022. Categorical variables were analyzed by Chi-squared test, and survival was analyzed using Kaplan-Meier (KM) curves. Results: MECCC patients were 40.7% Hispanic and 20.6% Black, compared with 3% and 2%, respectively, in the landmark IMbrave 150 study. Median overall survival (mOS) on ICI was 9.0 months, 25.0 months for the 100 (51.5%) favorable-prognosis Child Pugh A (CPA) patients included in HCC clinical trials. Disease control rate (DCR) was 58.5% among 123 evaluable patients per mRECIST 1.1. Baseline liver function, as defined by CP and the Model for End-Stage Liver Disease-Sodium (MELD-Na), correlated with survival (p < 0.001). Hepatitis C Virus (HCV) and alcoholism were over-represented relative to National Cancer Institute (NCI) data (56.2% vs 4.7% and 38.7% vs 8.2%, respectively). HCV treatment correlated with prolonged survival in infected patients (p = 0.0017). AFP decline correlated with response (p = 0.001). Hispanic patients lived longer when clinical variables were controlled for (mOS 52 vs 23 months; p = 0.011). Conclusion: In an underserved HCC population, ICI yielded a DCR of 58.5% and low rates of severe toxicity. This work highlights ICI efficacy in minority groups, a need for earlier HCC diagnosis and for studies of genetic and environmental factors in Hispanics with HCC.

Biocomposite based on graphene oxide immobilized Pseudomonas psychrotolerans for the recovery of Y(III) in acid mine drainage.

Rare earth elements (REEs) recovery is a critical issue concerning both resource recovery and wastewater utilization. In this study, a new bio-composite was fabricated using graphene oxide immobilized Pseudomonas psychrotolerans (PP@GO), which was isolated from the soil of REEs mine. Results showed that 99.6% Y(III) was removed in 48 h and various characterization confirmed that S-S, -NH2, HPO42-, -OH and -COOH from extracellular polymeric substances (EPS) secreted by microorganisms formed complexation with Y(III). As well, the Y(III) adsorption best followed Freundlich isotherm and non-linear pseudo-second-order kinetic model having R2 of 0.985 and 0.996, respectively, demonstrating that the adsorption was governed by multilayered chemisorption. Additionally, the effectiveness of PP@GO was not limited to Y(III), where 27.9% of this substance was removed in acid mine drainage (AMD), also exhibited great adsorption for other REEs, such as Er (45.0%) and Ho (43.8%). Furthermore, the adsorption efficiency of Y(III) remained high (70.0%) after a 5th cycle, emphasizing the consistent stability of PP@GO. Finally, REEs adsorbed could be greatly desorbed by KNO3, like Sm (80.1%) and La (80.0%), which revealed that PP@GO has great potential to recover REEs in AMD. Overall, this study offers a promising strategy for the green and sustainable REEs recovery and wastewater treatment.

Establishment of a pathomic-based machine learning model to predict CD276 (B7-H3) expression in colon cancer.

CD276 is a promising prognostic indicator and an attractive therapeutic target in various malignancies. However, current methods for CD276 detection are time-consuming and expensive, limiting extensive studies and applications of CD276. We aimed to develop a pathomic model for CD276 prediction from H&E-stained pathological images, and explore the underlying mechanism of the pathomic features by associating the pathomic model with transcription profiles. A dataset of colon adenocarcinoma (COAD) patients was retrieved from the Cancer Genome Atlas (TCGA) database. The dataset was divided into the training and validation sets according to the ratio of 8:2 by a stratified sampling method. Using the gradient boosting machine (GBM) algorithm, we established a pathomic model to predict CD276 expression in COAD. Univariate and multivariate Cox regression analyses were conducted to assess the predictive performance of the pathomic model for overall survival in COAD. Gene Set Enrichment Analysis (GESA) was performed to explore the underlying biological mechanisms of the pathomic model. The pathomic model formed by three pathomic features for CD276 prediction showed an area under the curve (AUC) of 0.833 (95%CI: 0.784-0.882) in the training set and 0.758 (95%CI: 0.637-0.878) in the validation set, respectively. The calibration curves and Hosmer-Lemeshow goodness of fit test showed that the prediction probability of high/low expression of CD276 was in favorable agreement with the real situation in both the training and validation sets (P=0.176 and 0.255, respectively). The DCA curves suggested that the pathomic model acquired high clinical benefit. All the subjects were categorized into high pathomic score (PS) (PS-H) and low PS (PS-L) groups according to the cutoff value of PS. Univariate and multivariate Cox regression analysis indicated that PS was a risk factor for overall survival in COAD. Furthermore, through GESA analysis, we found several immune and inflammatory-related pathways and genes were associated with the pathomic model. We constructed a pathomics-based machine learning model for CD276 prediction directly from H&E-stained images in COAD. Through integrated analysis of the pathomic model and transcriptomics, the interpretability of the pathomic model provide a theoretical basis for further hypothesis and experimental research.