Transposon-based oncogene integration in Abcb4(Mdr2)-/- mice recapitulates high susceptibility to cholangiocarcinoma in primary sclerosing cholangitis.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is a dreaded complication of primary sclerosing cholangitis (PSC), difficult to diagnose and associated with high mortality. Lack of animal models of CCA recapitulating the hepatic microenvironment of sclerosing cholangitis hinders development of novel treatments. Here we sought to develop such PSC-associated CCA model in mice. METHODS: Ten-week-old Mdr2-/- mice with congenital PSC-like disease, and healthy wild-type littermates were subjected to either modified retrograde biliary instillation or hydrodynamic tail vein injection of sleeping beauty transposon-transposase plasmid system with activated AKT (myr-AKT) and Yap (YapS127A) protooncogenes (SB AKT/YAP1). The role of TGFß was interrogated via ALK5 inhibitor (SB-525334) administration. Tumor phenotype, burden and desmoplastic reaction were analyzed histologically and via RNA-seq. RESULTS: While SB AKT/YAP1 plasmids via retrograde biliary injection caused tumors in Mdr2-/-, only 26.67% (4/15) of these tumors were CCA. Alternatively, hydrodynamic tail vein injection of SB AKT/YAP1 resulted in robust tumorigenesis in all fibrotic Mdr2-/- mice with high CCA burden compared to healthy mice. Tumors phenotypically resembled human CCA, expressed multiple CCA (but not hepatocellular carcinoma) markers, and exhibited a profound desmoplastic reaction. RNA-seq analysis revealed profound transcriptional changes in CCA evolving in PSC-like context, with specific alterations in multiple immune pathways. Pharmacological TGFß inhibition led to enhanced immune cell tumor infiltration, reduced tumor burden and suppressed desmoplastic collagen accumulation compared to placebo CONCLUSION: We established a new high-fidelity cholangiocarcinoma model in mice, termed SB CCA.Mdr2-/-, which recapitulates the increased susceptibility to CCA in the setting of biliary injury and fibrosis observed in PSC. Through transcriptomics and pharmacological studies, we show dysregulation of multiple immune pathways and TGFß signaling as potential drivers of CCA in PSC-like microenvironment. IMPACT AND IMPLICATIONS: There is a lack of animal models for primary sclerosing cholangitis (PSC) related cholangiocarcinoma (PSC-CCA). We have developed and characterized a new mouse model of PSC-CCA, termed SB CCA.Mdr2-/-, which features reliable tumor induction in PSC-like background of biliary injury and fibrosis. Global gene expression alterations were identified and standardized tools, including automated whole slide image analysis methodology for tumor burden and feature analysis, were established to enable systematic research into PSC-CCA biology and formal pre-clinical drug testing.

Refining the targeted population and achieving better for colorectal cancer screening.

This editorial comments on the article entitled "Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?" by Agatsuma et al, who conducted a retrospective study aiming at clarifying the stage at colorectal cancer (CRC) diagnosis based on different diagnostic routes. We share our opinion about CRC screening programs. The current situation suggests the need for a more specific and targeted population for CRC screening.

CBLL1 promotes endometrial stromal cell senescence via inhibiting PTEN in recurrent spontaneous abortion.

Recurrent spontaneous abortion (RSA) is a common pregnancy-related disorder. Cbl proto-oncogene like 1 (CBLL1) is an E3 ubiquitin ligase, which has been reported to vary with the menstrual cycle in the endometrium. However, whether CBLL1 is involved in the occurrence and development of RSA remains unclear. This study aimed to investigate the effects of CBLL1 on RSA. We analyzed the expression of CBLL1 in the decidua of RSA patients, as well as its functional effects on cellular senescence, oxidative stress, and proliferation of human endometrial stromal cells (HESCs). RNA sequencing was employed to identify a key downstream target gene regulated by CBLL1. We found that CBLL1 was upregulated in the decidua of RSA patients. Additionally, overexpression of CBLL1 promoted HESC senescence, increased oxidative stress levels, and inhibited proliferation. Phosphatase and tensin homolog located on chromosome 10 (PTEN) was identified as one of the important downstream target genes of CBLL1. In vivo experiments demonstrated that CBLL1 overexpression in the endometrium caused higher embryo absorption rate in mice. Consequently, elevated CBLL1 expression is a potential cause of RSA, representing a novel therapeutic target for RSA.

Enhancing irrigation water quality efficiently with potassium feldspar-derived adsorbent: Heavy metal detoxification and nutrient augmentation.

The pollution of Pb2+ and Cd2+ in both irrigation water and soil, coupled with the scarcity of vital mineral nutrition, poses a significant hazard to the security and quality of agricultural products. An economical potassium feldspar-derived adsorbent (PFDA) was synthesized using potassium feldspar as the main raw material through ball milling-thermal activation technology to solve this problem. The synthesis process is cost-effective and the resulting adsorbent demonstrates high efficiency in removing Pb2+ and Cd2+ from water. The removal process is endothermic, spontaneous, and stochastic, and follows the quasi-second-order kinetics, intraparticle diffusion, and Langmuir model. The adsorption and elimination of Pb2+ and Cd2+ is largely dependent on monolayer chemical sorption. The maximum removal capacity of PFDA for Pb2+ and Cd2+ at room temperature is 417 and 56.3 mg·g-1, respectively, which is superior to most mineral-based adsorbents. The desorption of Pb2+/Cd2+ on PFDA is highly challenging at pH≥3, whereas PFDA and Pb2+/Cd2+ are recyclable at pH≤0.5. When Pb2+ and Cd2+ coexisted, Pb2+ was preferentially removed by PFDA. In the case of single adsorption, Pb2+ was mainly adsorbed onto PFDA as Pb2SiO4, PbSiO3·xH2O, Pb3SiO5, PbAl2O4, PbAl2SiO6, PbAl2Si2O8, Pb2SO5, and PbSO4, whereas Cd2+ was primarily adsorbed as CdSiO3, Cd2SiO4, and Cd3Al2Si3O12. After the complex adsorption, the main products were PbSiO3·xH2O, PbAl2Si2O8, Pb2SiO4, Pb4Al2Si2O11, Pb5SiO7, PbSO4, CdSiO3, and Cd3Al2Si3O12. The forms of mineral nutrients in single and complex adsorption were different. The main mechanisms by which PFDA removed Pb2+ and Cd2+ were chemical precipitation, complexation, electrostatic attraction, and ion exchange. In irrigation water, the elimination efficiencies of Pb2+ and Cd2+ by PFDA within 10 min were 96.0 % and 70.3 %, respectively, and the concentrations of K+, Si4+, Ca2+, and Mg2+ increased by 14.0 %, 12.4 %, 55.7 %, and 878 %, respectively, within 60 min. PFDA holds great potential to replace costly methods for treating heavy metal pollution and nutrient deficiency in irrigation water, offering a sustainable, cost-effective solution and paving a new way for the comprehensive utilization of potassium feldspar.

Ultrasound-Mediated Lysozyme Microbubbles Targeting NOX4 Knockdown Alleviate Cisplatin-Exposed Cochlear Hair Cell Ototoxicity.

The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) protein plays an essential role in the cisplatin (CDDP)-induced generation of reactive oxygen species (ROS). In this study, we evaluated the suitability of ultrasound-mediated lysozyme microbubble (USMB) cavitation to enhance NOX4 siRNA transfection in vitro and ex vivo. Lysozyme-shelled microbubbles (LyzMBs) were constructed and designed for siNOX4 loading as siNOX4/LyzMBs. We investigated different siNOX4-based cell transfection approaches, including naked siNOX4, LyzMB-mixed siNOX4, and siNOX4-loaded LyzMBs, and compared their silencing effects in CDDP-treated HEI-OC1 cells and mouse organ of Corti explants. Transfection efficiencies were evaluated by quantifying the cellular uptake of cyanine 3 (Cy3) fluorescein-labeled siRNA. In vitro experiments showed that the high transfection efficacy (48.18%) of siNOX4 to HEI-OC1 cells mediated by US and siNOX4-loaded LyzMBs significantly inhibited CDDP-induced ROS generation to almost the basal level. The ex vivo CDDP-treated organ of Corti explants of mice showed an even more robust silencing effect of the NOX4 gene in the siNOX4/LyzMB groups treated with US sonication than without US sonication, with a marked abolition of CDDP-induced ROS generation and cytotoxicity. Loading of siNOX4 on LyzMBs can stabilize siNOX4 and prevent its degradation, thereby enhancing the transfection and silencing effects when combined with US sonication. This USMB-derived therapy modality for alleviating CDDP-induced ototoxicity may be suitable for future clinical applications.

Association of Thrombocytopenia With Disease Burden, High-Risk Cytogenetics, and Survival in Newly Diagnosed Multiple Myeloma Patients Treated With Novel Therapies.

BACKGROUND: The effect of thrombocytopenia has not been studied in the era of novel treatments in multiple myeloma (MM). OBJECTIVE: To evaluate the clinical characteristics and outcomes in MM patients presenting with thrombocytopenia. MATERIALS: Newly diagnosed MM patients between 2008 and 2018 who received at least 2 novel agents at induction. Thrombocytopenia was defined as a platelet count of less than < 150,000/mm3. RESULTS: A total of 648 patients were identified. Thrombocytopenia was found in 120 patients (18.5%). Baseline disease characteristics associated with higher rates of thrombocytopenia at baseline included IgA myeloma, P < .01, ISS 3 versus 1 or 2, P < .01, R-ISS 3 versus 1 or 2, P < .01, renal failure (CrCl < 30 mL/min), P < .01, hypercalcemia (Ca > 11.5 mg/dL), P < .01, elevated LDH, P < .03, anemia (Hb < 10 g/dL), P < .01, higher serum monoclonal protein, P < .02, and > 60% plasma cells in the bone marrow, P < .01. Thrombocytopenia was more prevalent across patients with t(4;14) and t(14;16), but was not associated with an overall high-risk fluorescence in situ hybridization (FISH) classification. Median OS was significantly lower among patients with thrombocytopenia (64.4 vs. 145.0 months, P < .01). In multivariable Cox regression, thrombocytopenia was associated with mortality (HR = 2.45, 95% CI, 1.7-3.6) independently of age, sex, high-risk FISH, ISS stage, response at induction, percentage of plasma cells in the BM, and anemia. CONCLUSION: We found that thrombocytopenia was seen among one-fifth of MM patients and was more common in patients with (t[4; 14] and t[14; 16]). Thrombocytopenia had an independent association with worse survival.

Development of fermented Atemoya (Annona cherimola × Annona squamosa)-Amazake increased intestinal next-generation probiotics.

Akkermansia muciniphila and Faecalibacterium prausnitzii are next-generation probiotics, which has been reported to protect disease and effectively utilize various carbohydrates (starch and pectin) as nutrients for growth. Atemoya exhibiting fruity flavor, which is suitable for enhancing aroma and attenuating unpleasant taste caused by the koji metabolites. Results indicated that malic acid was increased (from 42.4 to 70.1 mg/100 g) in fermented Atemoya-Amazake. In addition, fermented Atemoya-Amazake elevated growthes in A. muciniphila and F. prausnitzii. Similarly, the populations of Parabacteroides (5.7 fold) and Akkermansia (1.66 fold) were elevated by fermented Atemoya-Amazake treatment in an in vitro simulated gastrointestinal system compared to the control group. Results revealed that fermented Atemoya-Amazake modulated the intestinal microbiota through increasing the production of short-chain fatty acids (exhibiting anti-pathogenic activity) for 2.1, 2.5, 2.6, and 2.1 folds in acetic acid, propionic acid, isobutyric acid, and butyric acid, respectively; suggesting this fermented Atemoya-Amazake could be applied in intestinal protection.

Predicting soil thermal properties in freeze-thaw cycles using EFAttNet: A comparative analysis.

This study investigates the thermal conductivity (λ) and volumetric heat capacity (C) of sandy soil samples under a variety of conditions, including freeze-thaw cycles at temperatures both above and below zero and differing moisture levels. To estimate these thermal properties, a novel predictive model, EFAttNet, was developed, which utilizes custom-designed embedding and attention-based fusion networks. When compared to traditional de Vries empirical models and other baseline algorithms, EFAttNet demonstrated superior accuracy. Preliminary measurements showed that λ values increased linearly with moisture content but decreased with temperature, whereas C values exhibited a rising trend with both moisture content and freezing temperature. Following freeze-thaw cycles, both λ and C were positively influenced by moisture content and freezing temperature. The EFAttNet-based model proved highly accurate in predicting thermal properties, particularly effective at capturing nonlinear relationships among the influencing factors. Among these factors, the degree of saturation had the most significant impact, followed by the number of freeze-thaw cycles, subzero temperatures, porosity, and moisture content. Notably, dry density exerted minimal influence on thermal properties, likely due to the overriding effects of other factors or specific soil characteristics, such as particle size distribution or mineralogical composition. These findings have significant implications for construction and engineering projects, especially in terms of sustainability and energy efficiency. The demonstrated accuracy of the EFAttNet-based model in estimating thermal properties under various conditions holds promise for practical applications. Although focused on specific soil types and conditions, the insights gained can guide further research and development in managing soil thermal properties across diverse environments, thereby enhancing our understanding and application in this field.

Valorization of broiler edible byproducts: a chicken-liver hydrolysate with hepatoprotection against binge drinking.

Over 10,000 metric-ton broiler livers are produced annually in Taiwan. Concerning unpleasant odor and healthy issue, broiler livers are not attractive to consumers. Although the patented chicken-liver hydrolysates (CLHs) through pepsin digestion possess several biofunctionalities, there is no study on hepatoprotection of CLH-based formula capsule (GBHP01) against binge drinking (Whiskey, 50% Alc./Vol.). GBHP01 led to an accelerated blood-alcohol clearance in rats, as evidenced by lowering blood-alcohol increment within 0 to 4 h, increasing blood-alcohol decrement within 4 to 8 h, and smaller blood alcohol concentration areas under the curve (BAC AUC) in the 8-h period (p < 0.05). The ameliorative effects of GBHP01 against binge drinking in rats over 6 wk were attributed to accelerated alcohol metabolism by further increasing alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities while downregulating cytochrome P450 2E1 (CYP2E1) protein expression, elevating antioxidant capacity, decreasing zonula occludens-1 (ZO-1) protein decrement and serum endotoxin, and reducing inflammation related protein levels, that is, toll-like receptor 4 (TLR4) and mitogen-activated protein kinase (MAPK), and proinflammatory cytokines. The development of CLH supplements could not only enhance the added value of broiler livers through nutraceutical development but also offer a strategy to maximize the utilization of poultry processing residues, as shown in this study.

Family caregivers use a Hand-Under-Hand online course to improve the nutritional status of patients with severe dementia: A quasi-experimental study.

AIM: In Taiwan, over 90% of dementia patients received home care. Severe dementia-linked food refusal significantly affects nutrition, thereby straining caregivers. Family caregivers can reduce their burden by learning feeding and dementia nutrition online, thus preserving patient oral feeding. The study aim for family caregivers learn online Hand-Under-Hand (UH) techniques to ease feeding in severe dementia, enhancing nutrition and reducing their burden. METHODS: In this quasi-experimental study, participants in the experimental group received 2-h UH courses online, while the control group received their usual care. The primary outcome indicators were abnormal eating behavior, nutritional status, and caregiver burden, with outcomes tracked at 0, 1, and 3 months. At the neurology outpatient clinic of a medical center in Taipei, 65 dyads-comprising patients with severe dementia and their caregivers-were randomly assigned to groups. RESULTS: The study participants comprised 36 female and 29 male caregivers, with an average age of 58.09 years. The patient group included 43 females and 22 males, with a mean age of 83.32 years. Patients in the experimental group exhibited reduced abnormal eating behavior, and caregiver burden was reduced at 1 and 3 months, patients demonstrated improved nutritional status by month 3. CONCLUSIONS: The accessibility and convenience of online courses enabled family caregivers to use UH feeding techniques to effectively improve the nutritional status and correct the abnormal eating behavior of patients with dementia, while also decreasing caregiver burden. Geriatr Gerontol Int 2024; ••: ••-••.

Chronic recurrent multifocal osteomyelitis: Case report and review of the literature.

BACKGROUNDS: Chronic recurrent multifocal osteomyelitis (CRMO) is a rare inflammatory disease. OBJECTIVE: This report aims to analyze the clinical characteristics of CRMO and enhance clinicians' comprehension. We present 3 atypical cases, highlighting their unique clinical features, diagnostic challenges, and effective treatment strategies. METHODS: We retrieved 3 CRMO cases in our hospital from September 2019 to August 2022. The clinical features were analyzed retrospectively, and relevant literatures were reviewed. RESULTS: All 3 cases initially presented with bone pain, normal leucocyte counts, negative rheumatoid factors and no signs of sclerotic or hyperostotic lesions. Case 1, a 12-year-old girl, exhibited concurrent acne on the forehead and historic necrotizing lymphadenitis, a previously unreported association with CRMO. Case 2, a 14-year-old boy, tested positive for human leukocyte antigen-B27 and displayed scoliosis along with multifocal osteomyelitis. Case 3, a 9-year-old girl, presented with scoliosis, and chest computed tomography revealed changes in the T8 vertebral body, initially suggesting Langerhans cell histiocytosis. Bone biopsy was conducted in case 1 and case 3, revealing chronic inflammation. All 3 cases affected long bones, pelvis, and vertebra, involving 8, 6 and 5 bones, respectively, identified by magnetic resonance imaging. Genetic analysis was undertaken in cases 1 and 2 but no pathogenic mutations were identified. Upon the confirmation of a CRMO diagnosis, all patients were initiated on a treatment regimen comprising nonsteroidal anti-inflammatory drugs and tumor necrosis factor-α inhibitors. In cases 1 and 2, due to the severity of their bone pain, they were also administered to disease-modifying anti-rheumatic drugs, specifically methotrexate. All 3 patients achieved remission of bone pain. To gain a more comprehensive understanding of CRMO, we conducted a thorough review of relevant literature. CONCLUSION: CRMO is a rare autoinflammatory bone disorder with diverse clinical presentations and a lack of specific laboratory tests, which leads to potency to misdiagnosis or delayed diagnosis. By raising awareness and improving diagnostic criteria, physicians are now better equipped to identify CRMO. We contribute to share our understanding of CRMO by presenting 3 cases with untypical clinical features, highlighting the importance of recognizing this rare condition for timely and effective management.

Clinical features associated with poor response and early relapse following BCMA-directed therapies in multiple myeloma.

Three classes of BCMA-directed therapy (BDT) exist: antibody drug-conjugates (ADCs), CAR-T, and T-cell engagers (TCEs), each with distinct strengths and weaknesses. To aid clinicians in selecting between BDTs, we reviewed myeloma patients treated at Mayo Clinic with commercial or investigational BDT between 2018-2023. We identified 339 individuals (1-exposure = 297, 2-exposures = 38, 3-exposures = 4) who received 385 BDTs (ADC = 59, TCE = 134, CAR-T = 192), with median follow-up of 21-months. ADC recipients were older, with more lines of therapy (LOT), and penta-refractory disease. Compared to ADCs, CAR-T (aHR = 0.29, 95%CI = 0.20-0.43) and TCEs (aHR = 0.62, 95%CI = 0.43-0.91) had better progression-free survival (PFS) on analysis adjusted for age, the presence of extramedullary (EMD), penta-refractory disease, multi-hit high-risk cytogenetics, prior BDT, and the number of LOT in the preceding 1-year. Likewise, compared to ADCs, CAR-T (aHR = 0.28, 95%CI = 0.18-0.44) and TCEs (aHR = 0.60, 95%CI = 0.39-0.93) had superior overall survival. Prior BDT exposure negatively impacted all classes but was most striking in CAR-T, ORR 86% vs. 50% and median PFS 13-months vs. 3-months. Of relapses, 54% were extramedullary in nature, and a quarter of these cases had no history of EMD. CAR-T demonstrates superior efficacy and where feasible, should be the initial BDT. However, for patients with prior BDT or rapidly progressive disease, an alternative approach may be preferable.

Qualification rate and associated factors regarding COVID-19 clinical skills training based on scenario simulation teaching to medical staffs in China: a hospital-based cross-sectional study.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has accentuated the need for effective clinical skills training in infectious diseases. This study aimed to explore the influencing factors of infectious disease clinical skills training based on scenario simulation teaching for medical staff in China. METHODS: This hospital-based, cross-sectional study was conducted at the Third People's Hospital of Shenzhen between March and December 2022. Scenario simulation teaching was applied, and factors such as gender, educational level, professional background, and previous experience were examined to determine their impact on qualification outcomes. RESULTS: The study included participants primarily between the ages of 20-40 years, with a higher proportion of women holding university degrees. Nurses and physicians were more likely to qualify, indicating the significance of professional backgrounds. Women showed a higher likelihood of qualifying than men and higher educational attainment correlated with better qualification rates. Prior experience with protective clothing in isolation wards was a significant determinant of successful qualification. Multivariate analysis underscored the influence of sex, education, and previous experience on training effectiveness. CONCLUSION: Scenario simulation is an effective strategy for training clinical skills in treating infectious diseases. This study highlights the importance of considering sex, education, professional background, and prior experience when designing training programs to enhance the efficacy and relevance of infectious disease training.

ChatGPT's Role in Gerontology Research.

BACKGROUND: ChatGPT and other ChatBots have emerged as tools for interacting with information in manners resembling natural human speech. Consequently, the technology is used across various disciplines, including business, education, and even in biomedical sciences. There is a need to better understand how ChatGPT can be used to advance gerontology research. Therefore, we evaluated ChatGPT responses to questions on specific topics in gerontology research, and brainstormed recommendations for its use in the field. METHODS: We conducted semi-structured brainstorming sessions to identify uses of ChatGPT in gerontology research. We divided a team of multidisciplinary researchers into four topical groups: a) gero-clinical science, b) basic geroscience, c) informatics as it relates to electronic health records (EHR), and d) gero-technology. Each group prompted ChatGPT on a theory-, methods-, and interpretation-based question and rated responses for accuracy and completeness based on standardized scales. RESULTS: ChatGPT responses were rated by all groups as generally accurate. However, the completeness of responses was rated lower, except by members of the informatics group, who rated responses as highly comprehensive. CONCLUSIONS: ChatGPT accurately depicts some major concepts in gerontological research. However, researchers have an important role in critically appraising the completeness of its responses. Having a single generalized resource like ChatGPT may help summarize the preponderance of evidence in the field to identify gaps in knowledge and promote cross-disciplinary collaboration.

The impact of fetuin-A on predicting aortic arch calcification: secondary analysis of a community-based survey.

Introduction: Atherosclerotic cardiovascular disease is associated with a high mortality rate due to vascular calcification. The role of fetuin-A in aortic arch calcification (AAC) is less well understood. Methods: An analysis of secondary biomarkers was performed on 800 individuals from the biobank using the community database. AAC was defined by radiologists based on imaging. Multiple variables logical analysis was used for risk analysis. Results: A total of 736 individual samples were collected based on age and gender. The average age is 65 ± 10 years, and half the population comprises men. In spite of similar body weight, renal function, and hepatic function, the AAC group had higher blood pressure and fetuin-A levels independently: systolic blood pressure (SBP) index ≥130 mmHg [adjusted odds ratio (aOR) 1.85, 95% confidence interval (CI) 1.34-2.57, p = 0.002] and fetuin-A (aOR 0.62, 95% CI 0.50-0.76, p < 0.001). Moreover, it is evident that AAC can be predicted more accurately when combined with SBP ≥130 mmHg and a low fetuin-A level (<358 µg/ml: aOR 5.39, 95% CI 3.21-9.08) compared with the reference. Conclusion: Low fetuin-A levels are significantly correlated with AAC while there is an increased association between vascular calcification and coexisting hypertension.

Enhancing COVID-19 booster vaccination among the elderly through text message reminders.

The BOOST (Booster promotion for older outpatients using SMS text reminders) program at Taipei Veterans General Hospital assessed the effectiveness of text message reminders in enhancing COVID-19 booster vaccination rates among the elderly, guided by the Health Belief Model (HBM). Targeting patients aged 65 and above, eligible yet unvaccinated for a COVID-19 booster, this cohort study sent personalized reminders a week prior to their scheduled appointments between April 18, 2022, and May 12, 2022, acting as cues to action to enhance vaccination uptake by overcoming perceived barriers and raising awareness of benefits. Over 5 weeks, the study observed a 38% increase in vaccination rate among 3,500 eligible patients, markedly surpassing the concurrent national rate increase of 4% for the same demographic. The majority of vaccinations occurred within two weeks after the reminder, illustrating the effectiveness of the strategy. Cox regression analysis identified age and time since last vaccination as significant predictors of responsiveness, with those aged 65-74 and 75-84 showing higher uptake, particularly when reminders were sent within 4 months after the last dose. A single reminder proved to be effective. The findings of this study demonstrate the potential of SMS reminders to promote COVID-19 vaccination among the elderly through the strategic use of HBM principles, suggesting a feasible and effective approach to public health communication.

Outcomes of r/r B-cell NHL patients with limited (<5 Sites) pre-CART Disease Bridged With or Without Radiotherapy.

Unirradiated relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (NHL) patients who undergo anti-CD19 Chimeric Antigen Receptor T-cell Therapy (CART) have a predominant localized pattern of relapse, the significance of which is heightened in individuals with limited/localized pre-CART disease. This study reports on the outcomes of r/r NHL patients with limited (<5 involved sites) disease bridged with or without radiotherapy (BRT). A multi-center retrospective review of 150 patients with r/r NHL who received CART with <5 disease sites prior to leukapheresis was performed. Bridging treatment, if any, was administered between leukapheresis and CART infusion. Study endpoints included relapse free-survival (RFS), event-free survival (EFS) and overall survival (OS). Prior to CART infusion, 48 (32%) patients received BRT and 102 (68%) did not. The median follow-up was 21 months. Following CART infusion, BRT patients had higher objective response (92% vs 78%, p=0.046) and sustained complete response (54% vs 33%, p=0.015) rates. Local relapse in sites present prior to CART was lower in the BRT group (21% vs. 46%, p=0.003). BRT patients had improved 2-year RFS (53% vs 44%, p=0.023) and 2-year EFS (37% vs 34%, p=0.039) compared to no BRT patients. The impact of BRT was most prominent in patients who had ≤2 pre-CART involved disease sites, with 2-year RFS of 62% in patients who received BRT compared to 42% in those who did not (p=0.002). BRT prior to CART for patients with limited (<5 involved disease sites) r/r NHL improves response rate, local control, RFS, and EFS without causing significant toxicities.

Innovative Microbial Immobilization Strategy for Di-n-Butyl Phthalate Biodegradation Using Biochar-Calcium Alginate-Waterborne Polyurethane Composites.

Di-n-butyl phthalate (DBP) is a prevalent phthalate ester widely used as a plasticizer, leading to its widespread presence in various environmental matrices. This study presents an innovative microbial immobilization strategy utilizing biochar, calcium alginate (alginate-Ca, (C12H14CaO12)n), and waterborne polyurethane (WPU) composites to enhance the biodegradation efficiency of DBP. The results revealed that rice husk biochar, pyrolyzed at 300 °C, exhibits relatively safer and more stable physical and chemical properties, making it an effective immobilization matrix. Additionally, the optimal cultural conditions for Bacillus aquimaris in DBP biodegradation were identified as incubation at 30 °C and pH 7, with the supplementation of 0.15 g of yeast extract, 0.0625 g of glucose, and 1 CMC of Triton X-100. Algal biotoxicity results indicated a significant decrease in biotoxicity, as evidenced by an increase in chlorophyll a content in Chlorella vulgaris following DBP removal from the culture medium. Finally, microbial community analysis demonstrated that encapsulating B. aquimaris within alginate-Ca and WPU layers not only enhanced DBP degradation, but also prevented ecological competition from indigenous microorganisms. This novel approach showcases the potential of agricultural waste utilization and microbial immobilization techniques for the remediation of DBP-contaminated environments.