UM171 suppresses breast cancer progression by inducing KLF2.

PURPOSE: Breast cancer is the most frequent cancer in women with significant death rate. Morbidity is associated with drug resistance and metastasis. Development of novel drugs is unmet need. The aim of this study is to show potent anti-neoplastic activity of the UM171 compound on breast cancer cells and its mechanism of action. METHODS: The inhibitory effect of UM171 on several breast cancer (BC) cell lines was examined using MTT and colony-forming assays. Cell cycle and apoptosis assays were utilized to determine the effect of UM171 on BC cell proliferation and survival. Wound healing scratch and transwell migration assays were used to examine the migration of BC cell lines in culture. Xenograft of mouse model with 4T1 cells was used to determine inhibitory effect of UM171 in vivo. Q-RT-PCR and western blotting were used to determine the expression level of genes effected by UM171. Lentivirus-mediated shRNAs were used to knockdown the expression of KLF2 in BC cells. RESULTS: UM171 was previously identified as a potent agonist of human hematopoietic stem cell renewal and inhibitor of leukemia. In this study, UM171 was shown to inhibit the growth of multiple breast cancer cell lines in culture. UM171-mediated growth inhibition was associated with the induction of apoptosis, G2/M cell cycle arrest, lower colony-forming capacity, and reduced motility. In a xenotransplantation model of mouse triple-negative breast cancer 4T1 cells injected into syngeneic BALB/c mice, UM171 strongly inhibited tumor growth at a level comparable to control paclitaxel. UM171 increased the expression of the three PIM genes (PIM1-3) in breast cancer cells. Moreover, UM171 strongly induced the expression of the tumor suppressor gene KLF2 and cell cycle inhibitor P21CIP1. Accordingly, knockdown of KLF2 using lentivirus-mediated shRNA significantly attenuated the growth suppressor activity of UM171. As PIM1-3 act as oncogenes and are involved in breast cancer progression, induction of these kinases likely impedes the inhibitory effect of KLF2 induction by UM171. Accordingly, combination of UM171 with a PAN-PIM inhibitor LGH447 significantly reduced tumor growth in culture. CONCLUSION: These results suggested that UM171 inhibited breast cancer progression in part through activation of KLF2 and P21. Combination of UM171 with a PAN-PIM inhibitor offer a novel therapy for aggressive forms of breast cancer.

Transdermal microarrayed electroporation for enhanced cancer immunotherapy based on DNA vaccination.

Despite the tremendous clinical potential of nucleic acid-based vaccines, their efficacy to induce therapeutic immune response has been limited by the lack of efficient local gene delivery techniques in the human body. In this study, we develop a hydrogel-based organic electronic device (µEPO) for both transdermal delivery of nucleic acids and in vivo microarrayed cell electroporation, which is specifically oriented toward one-step transfection of DNAs in subcutaneous antigen-presenting cells (APCs) for cancer immunotherapy. The µEPO device contains an array of microneedle-shaped electrodes with pre-encapsulated dry DNAs. Upon a pressurized contact with skin tissue, the electrodes are rehydrated, electrically triggered to release DNAs, and then electroporate nearby cells, which can achieve in vivo transfection of more than 50% of the cells in the epidermal and upper dermal layer. As a proof-of-concept, the µEPO technique is employed to facilitate transdermal delivery of neoantigen genes to activate antigen-specific immune response for enhanced cancer immunotherapy based on a DNA vaccination strategy. In an ovalbumin (OVA) cancer vaccine model, we show that high-efficiency transdermal transfection of APCs with OVA-DNAs induces robust cellular and humoral immune responses, including antigen presentation and generation of IFN-γ+ cytotoxic T lymphocytes with a more than 10-fold dose sparing over existing intramuscular injection (IM) approach, and effectively inhibits tumor growth in rodent animals.

Translation and validation of the Chinese version of the BCPT Eight Symptom Scale (BESS) in patients with breast cancer.

Objective: This study aimed to translate the Breast Cancer Prevention Trial Eight Symptom Scale (BESS) into Chinese and subsequently examine the latent constructs and psychometric properties of the Chinese BESS (C-BESS) among patients with breast cancer. Methods: In Phase 1, the BESS was translated from English into Chinese using the FACIT translation method. An expert panel was convened to assess the content validity, and pilot testing was performed with 20 patients with breast cancer. In Phase 2, a total of 427 patients with breast cancer from four Grade-A public hospitals in China were recruited to examine psychometric properties of the C-BESS. The internal consistency was evaluated based on the Cronbach's α, and the construct validity was tested using confirmatory factor analysis, convergent validity, and discriminant validity. Results: The C-BESS demonstrated satisfactory content validity index (item-level content validity index [I-CVI]: 0.8-1.0; scale-level content validity index [S-CVI]: 0.97). The Cronbach's α value for the entire C-BESS scale was 0.92. Confirmatory factor analysis indicated that eight-factor structure of the C-BESS was a good fit to the data (CFI = 0.959, AGFI = 0.904, RMSEA = 0.05, RMR = 0.029). The scale exhibited good convergent validity and discriminant validity. Conclusions: This study translated and validated the C-BESS for use in the Chinese population. The results demonstrate that the C-BESS exhibits good reliability and validity, with ideal psychometric properties for assessing the symptom burden in Chinese patients with breast cancer. This tool can be effectively integrated into the routine symptom monitoring of patients with breast cancer in China, helping Chinese clinical professionals in conducting comprehensive assessments of symptom burden.

Ouabain, ATPase inhibitor, potentially enhances the effect of polyhexamethylene biguanide on Acanthamoeba castellanii.

Acanthamoeba, a free-living amoeba, is commonly found in various natural environments, such as rivers and soil, as well as in public baths, swimming pools, and sewers. Acanthamoeba can cause severe illness such as granulomatous amoebic encephalitis and Acanthamoeba keratitis (AK) in humans. AK, the most recognized disease, can cause permanent visual impairment or blindness by affecting the cornea. AK commonly affects contact lens wearers who neglect proper cleaning habits. The symptoms of AK include epithelial and stromal destruction, corneal infiltrate, and intense ocular pain, occasionally necessitating surgical removal of the entire eyeball. Current AK treatment involves the hourly application of eye drops containing polyhexamethylene biocide (PHMB). However, studies have revealed their ineffectiveness against drug-resistant strains. Acanthamoeba can form cysts as a survival mechanism in adverse environments, though the exact mechanism remains unknown. Our experiments revealed that sodium P-type ATPase (ACA1_065450) is closely linked to encystation. In addition, various encystation buffers, such as MgCl2 or NaCl, induced the expression of P-type ATPase. Furthermore, we used ouabain, an ATPase inhibitor, to inhibit the Na+/K+ ion pump, consequently decreasing the encystation rate of Acanthamoeba. Our primary objective is to develop an advanced treatment for AK. We anticipate that the combination of ouabain and PHMB may serve as an effective therapeutic approach against AK in the future.

An intricate regulatory circuit between FLI1 and GATA1/GATA2/LDB1/ERG dictates erythroid vs. megakaryocytic differentiation.

During hematopoiesis, megakaryocytic erythroid progenitors (MEPs) differentiate into megakaryocytic or erythroid lineages in response to specific transcriptional factors, yet the regulatory mechanism remains to be elucidated. Using the MEP­like cell line HEL western blotting, RT­qPCR, lentivirus­mediated downregulation, flow cytometry as well as chromatin immunoprecipitation (ChIp) assay demonstrated that the E26 transformation­specific (ETS) transcription factor friend leukemia integration factor 1 (Fli­1) inhibits erythroid differentiation. The present study using these methods showed that while FLI1­mediated downregulation of GATA binding protein 1 (GATA1) suppresses erythropoiesis, its direct transcriptional induction of GATA2 promotes megakaryocytic differentiation. GATA1 is also involved in megakaryocytic differentiation through regulation of GATA2. By contrast to FLI1, the ETS member erythroblast transformation­specific­related gene (ERG) negatively controls GATA2 and its overexpression through exogenous transfection blocks megakaryocytic differentiation. In addition, FLI1 regulates expression of LIM Domain Binding 1 (LDB1) during erythroid and megakaryocytic commitment, whereas shRNA­mediated depletion of LDB1 downregulates FLI1 and GATA2 but increases GATA1 expression. In agreement, LDB1 ablation using shRNA lentivirus expression blocks megakaryocytic differentiation and modestly suppresses erythroid maturation. These results suggested that a certain threshold level of LDB1 expression enables FLI1 to block erythroid differentiation. Overall, FLI1 controlled the commitment of MEP to either erythroid or megakaryocytic lineage through an intricate regulation of GATA1/GATA2, LDB1 and ERG, exposing multiple targets for cell fate commitment and therapeutic intervention.

VPg-based bidirectional synthetic mRNA circuits enable orthogonal protein regulation for high-resolution cell separation.

Synthetic mRNA circuits commonly sense input to produce binary output signals for cell separation. Based on virus-origin cap-independent translation initiation machinery and RBP-aptamer interaction, we designed smart synthetic mRNA-based circuits that sense single input molecules to bidirectionally tune output signals in an orthogonal manner, enabling high-resolution separation of cell populations.

Modified technique of Hepatojejunostomy for biliary tract reconstruction after resection of tumors affecting the perihilar region: a case series.

BACKGROUNDS: Radical resection is the most effective treatment for perihilar tumors. Biliary tract reconstruction after resection is one of the key steps in this surgery. Mucosa-to-mucosa cholangiojejunostomy is traditionally performed, in which the bile ducts at the resection margin are separately anastomosed to the jejunum. However, this approach is associated with long operative time and high risk of postoperative complications. The present study presents a modified technique of hepatojejunostomy and its outcomes. METHODS: The data of patients who underwent hepatojejunostomy using the modified technique at the Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing, China, from January 2016 to December 2021, were retrospectively analyzed. RESULTS: A total of 13 patients with perihilar tumors underwent R0 resection and bilioenteric reconstruction using the modified hepatojejunostomy technique during the study period. During the operation, the alignment of the bile duct stumps was improved, the posterior wall of the anastomosis was reinforced, internal stents were placed in the smaller bile ducts, external stents were placed in the larger bile ducts, and hepatojejunostomy was performed using 4 - 0 prolene. No serious postoperative complications, such as death or bile leakage, occurred during the hospitalization. Furthermore, there were no cases of biliary stricture or cholangitis after the six-month follow-up period. CONCLUSION: The modified hepatojejunostomy technique is a safe and effective technique of biliary reconstruction after the resection of perihilar tumors. This can be easily performed for difficult cases with multiple bile ducts that require reconstruction after resection.

Temporal Considerations in Brain Metastases Radiation Therapy: The Intersection of Chronobiology and Patient Profiles.

The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assessed circadian timing's impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. The aim of the study was to evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes and to identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities. An IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017-2021), receiving over 80% of treatments in the morning or afternoon, was performed. Survival analyses utilized Kaplan-Meier curves. This was a single-institution study involving patients receiving whole-brain radiotherapy. Demographic, disease, and socioeconomic parameters from electronic medical records were collected. Morning treatment (n = 158) showed a trend toward improved overall survival vs. afternoon (n = 79); the median survival was 158 vs. 79 days (p = 0.20, HR = 0.84, CI95% 0.84-0.91). Subgroup benefits for morning treatment in females (p = 0.04) and trends in controlled primary disease (p = 0.11) and breast cancer metastases (p = 0.08) were observed. Black patients exhibited diminished circadian influence. The present study emphasized chronobiological factors' relevance in brain metastases radiation therapy. Morning treatment correlated with improved survival, particularly in specific subgroups. Potential circadian influence disparities were identified, laying a foundation for personalized cancer therapy and interventions synchronizing circadian rhythms for enhanced treatment efficacy.

Heterogeneity of chemical modifications on RNA.

The chemical modifications of RNAs broadly impact almost all cellular events and influence various diseases. The rapid advance of sequencing and other technologies opened the door to global methods for profiling all RNA modifications, namely the "epitranscriptome." The mapping of epitranscriptomes in different cells and tissues unveiled that RNA modifications exhibit extensive heterogeneity, in type, amount, and in location. In this mini review, we first introduce the current understanding of modifications on major types of RNAs and the methods that enabled their discovery. We next discuss the tissue and cell heterogeneity of RNA modifications and briefly address the limitations of current technologies. With much still remaining unknown, the development of the epitranscriptomic field lies in the further developments of novel technologies.

FLI1 induces erythroleukemia through opposing effects on UBASH3A and UBASH3B expression.

BACKGROUND: FLI1 is an oncogenic transcription factor that promotes diverse malignancies through mechanisms that are not fully understood. Herein, FLI1 is shown to regulate the expression of Ubiquitin Associated and SH3 Domain Containing A/B (UBASH3A/B) genes. UBASH3B and UBASH3A are found to act as an oncogene and tumor suppressor, respectively, and their combined effect determines erythroleukemia progression downstream of FLI1. METHODS: Promoter analysis combined with luciferase assays and chromatin immunoprecipitation (ChIP) analysis were applied on the UBASH3A/B promoters. RNAseq analysis combined with bioinformatic was used to determine the effect of knocking-down UBASH3A and UBASH3B in leukemic cells. Downstream targets of UBASH3A/B were inhibited in leukemic cells either via lentivirus-shRNAs or small molecule inhibitors. Western blotting and RT-qPCR were used to determine transcription levels, MTT assays to assess proliferation rate, and flow cytometry to examine apoptotic index. RESULTS: Knockdown of FLI1 in erythroleukemic cells identified the UBASH3A/B genes as potential downstream targets. Herein, we show that FLI1 directly binds to the UBASH3B promoter, leading to its activation and leukemic cell proliferation. In contrast, FLI1 indirectly inhibits UBASH3A transcription via GATA2, thereby antagonizing leukemic growth. These results suggest oncogenic and tumor suppressor roles for UBASH3B and UBASH3A in erythroleukemia, respectively. Mechanistically, we show that UBASH3B indirectly inhibits AP1 (FOS and JUN) expression, and that its loss leads to inhibition of apoptosis and acceleration of proliferation. UBASH3B also positively regulates the SYK gene expression and its inhibition suppresses leukemia progression. High expression of UBASH3B in diverse tumors was associated with worse prognosis. In contrast, UBASH3A knockdown in erythroleukemic cells increased proliferation; and this was associated with a dramatic induction of the HSP70 gene, HSPA1B. Accordingly, knockdown of HSPA1B in erythroleukemia cells significantly accelerated leukemic cell proliferation. Accordingly, overexpression of UBASH3A in different cancers was predominantly associated with good prognosis. These results suggest for the first time that UBASH3A plays a tumor suppressor role in part through activation of HSPA1B. CONCLUSIONS: FLI1 promotes erythroleukemia progression in part by modulating expression of the oncogenic UBASH3B and tumor suppressor UBASH3A.

Symptom networks in older adults with cancer: A network analysis.

INTRODUCTION: Due to aging, older adults with cancer (OAC) may be confronted with a complex interplay of multiple age-related issues; coupled with receiving cancer treatment, OAC may experience multiple concurrent symptoms that require the identification of the core symptom for effective management. Constructing symptom networks will help in the identification of core symptoms and help achieve personalized and precise interventions. Currently, few studies have used symptom networks to identify core symptoms in OAC. Our objectives were to construct symptom networks of OAC, explore the core symptoms, and compare the differences in symptom networks among various subgroups. MATERIALS AND METHODS: Secondary analysis was performed using data from 485 OAC collected in 2021 from a cross-sectional survey named the Shanghai CANcer Survivor (SCANS) Report. The MD Anderson Symptom Inventory (MDASI) was used to assess the incidence and severity of cancer-related symptoms. We used the R package to construct symptom networks and identify the centrality indices. The network comparison test was used to compare network differences among the subgroups. RESULTS: The most common and severe symptoms reported were fatigue, disturbed sleep, and difficulty remembering. The network density was 0.718. Vomiting (rs = 1.81, rb = 2.13), fatigue (rs = 1.54, rb = 1.93), and sadness (rs = 0.81, rb = 0.69) showed the highest strength values, which suggested that these symptoms were more likely to co-occur with other symptoms. The network comparison tests showed significant differences in symptom network density between the subgroups categorized as survival "< 5 years" and survival "≥ 5 years" (p = 0.002), as well as between the those with comorbidities and those without comorbidities (p = 0.037). DISCUSSION: Our study identified symptom networks in 485 OAC. Vomiting, fatigue, and sadness were important symptoms in the symptom networks of OAC. The symptom networks differed among populations with different survival durations and comorbidities. Our network analysis provides a reference for future targeted symptom management and interventions in OAC. In the future, conducting dynamic research on symptom networks will be crucial to explore interaction mechanisms and change trends between symptoms.

Optimal Post-Operative Nalbuphine Dose Regimen: A Randomized Controlled Trial in Patients with Laparoscopic Cholecystectomy.

Background and Objectives: Optimal opioid analgesia is an excellent analgesia that does not present unexpected adverse effects. Nalbuphine, acting on the opioid receptor as a partial mu antagonist and kappa agonist, is considered a suitable option for patients undergoing laparoscopic surgery. Therefore, we aim to investigate the appropriate dosage of nalbuphine for post-operative pain management in patients with laparoscopic cholecystectomy. Materials and Methods: Patients were randomly categorized into low, medium, and high nalbuphine groups. In each group, a patient control device for post-operative pain control was programed with a low (0.05 mg/kg), medium (0.10 mg/kg), or high (0.20 mg/kg) nalbuphine dose as a loading dose and each bolus dose with a lockout interval of 7 min and without background infusion. Primary and secondary outcomes included the post-operative pain scale and nalbuphine consumption, and episodes of post-operative opioid-related adverse events and satisfactory scores. Results: The low-dosage group presented a higher initial self-reported pain score in comparison to the other two groups for the two hours post-op (p = 0.039) but presented lower nalbuphine consumption than the other two groups for four hours post-op (p = 0.047). There was no significant difference in the analysis of the satisfactory score and adverse events. Conclusions: An appropriate administration of nalbuphine could be 0.1 to 0.2 mg/kg at the initial four hours; this formula could be modified to a lower dosage (0.05 mg/kg) in the post-operative management of laparoscopic cholecystectomy.

ERK/STAT3 activation through CCL17/CCR4 axis-mediated type 2 cytokine-involved signaling pathways in Th2 cells regulates cutaneous drug reactions.

Cutaneous drug reactions (CDRs) are common drug-induced allergic reactions that cause severe consequences in HIV/AIDS patients. The CCL17/CCR4 axis is involved in the immune mechanism of allergic diseases, but its role in the CDRs has not been determined. Here, we aimed to determine the role of the CCL17/CCR4 axis and the underlying mechanism involved in CDRs. In this study, the serum cytokine levels in patients with CDR and healthy controls were measured. The CCL17-triggered allergic profile was screened via a PCR array. Apoptosis of keratinocytes cocultured with CCL17-stimulated Th2 cells was analyzed by flow cytometry. An NVP-induced rat CDR model was established, and dynamic inflammatory factor levels and Th2 cells in the peripheral blood of the rats were measured. Rat skin lesions and signaling pathways in Th2 cells were also analyzed. We showed that the serum CCL17 level was significantly upregulated in CDR patients (P = 0.0077), and the Th2 cell subgroup was also significantly elevated in the CDR rats. The CCL17/CCR4 axis induces Th2 cells to release IL-4 and IL-13 via the ERK/STAT3 pathway. The CCR4 antagonist compound 47 can alleviate rash symptoms resulting from NVP-induced drug eruption, Th2 cell subgroup, IL-4, and IL-13 and inhibit keratinocyte apoptosis. Taken together, these findings indicate that the CCL17/CCR4 axis mediates CDR via the ERK/STAT3 pathway in Th2 cells and type 2 cytokine-induced keratinocyte apoptosis.

The Emergence of the Potential Therapeutic Targets: Ultrasound-Based Radiomics in the Prediction of Human Epidermal Growth Factor Receptor 2-Low Breast Cancer.

RATIONALE AND OBJECTIVES: To evaluate whether ultrasound-based radiomics features can effectively predict HER2-low expression in patients with breast cancer (BC). MATERIAL AND METHODS: Between January 2021 and June 2023, patients who received US scans with pathologically confirmed BC in this multicenter study were included. In total, 383 patients from institution 1 were comprised of training set, 233 patients from institution 2 were comprised of validation set and 149 patients from institution 3 were comprised of external validation set. Radiomics features were derived from conventional ultrasound (US) images. The minimum redundancy and maximum relevancy and the least absolute shrinkage and selector operation algorithm were used to generate an US-based radiomics score (RS). Multivariable logistic regression analysis was used to select variables associated with HER2 expressions. The diagnostic performance of the RS was evaluated through the area under the receiver operating characteristic curve (AUC). RESULTS: In the training set, the RS yield an AUC of 0.81 (95%CI: 0.76-0.84) for differentiation HER2-zero from HER2-low and -positive cases, and performed well in validation set (AUC 0.84, 95%CI: 0.78-0.88) and external validation set (AUC 0.82, 95%CI: 0.73-0.90). In the subgroups analysis, the RS showed good performance in distinguishing HER2-zero from HER2 1 + , HER2 2 + and HER2-low tumors (AUC range, 0.79-0.87). CONCLUSION: The RS based on conventional US is proven effective for predicting HER2-low expression in BC.

Self-feedback loop-containing synthetic mRNA switches for controlled microRNA sensing.

Synthetic mRNA switches are powerful cell fate manipulation tools that sense cellular input molecules to directly control protein expression at the translational level. The lack of available switch designs that can mimic the natural sophisticated protein regulation is a fundamental issue that limits the application of synthetic mRNA switches. Here we report a new set of synthetic mRNA switches by incorporating self-feedback loop machineries to dynamically control protein expression levels upon sensing cellular microRNAs. We redesigned the coding region of the switch to express output protein along with mRNA regulatory proteins. RNA-binding proteins (RBPs) and RBP-binding RNA motifs (aptamers) guide the regulatory proteins to act on their own mRNAs, enhancing or flattening the effect of microRNA sensing. Importantly, we demonstrated that the switches with the positive feedback feature can enlarge a high-or-low microRNA effect into a nearly all-or-none pattern, substantially boosting the use of synthetic mRNA switches as high-performance microRNA sensors or binary cell regulation tools. We believe these novel mRNA switch designs provide new strategies to construct complex mRNA-based genetic circuits for future molecular sensing and cell engineering.

Suffering and adjustment: a grounded theory of the process of coping with financial toxicity among young women with breast cancer.

PURPOSE: To explore the process of coping with financial toxicity among young women with breast cancer and formulate a grounded theory that serves as a foundation for creating intervention strategies aimed at supporting cancer survivors. METHODS: A qualitative study using the Corbin and Strauss variant of grounded theory. A series of in-depth interviews were carried out with young women with breast cancer (n = 29) using the theoretical sampling method. We analyzed data by coding core categories in the patients' coping processes and developing theory around these categories. Data collection and analysis were performed simultaneously. RESULTS: A substantial theory of the process of coping with financial toxicity among young female breast cancer survivors was constructed. Two core concepts, suffering and adjustment, were identified. Young women with breast cancer suffered from financial toxicity, which was related to risk factors, coping resources, and unmet needs. To overcome financial toxicity, young women with breast cancer adjusted by reshaping consumption concept, re-dividing of family functions, re-planning of occupation career, and rebuilding life confidence. CONCLUSION: This qualitative study constructed a theory delineating the coping strategies employed by young women with breast cancer in response to financial toxicity, offering profound insights into the intricacies of cancer-related financial toxicity. Identifying risk factors, enhancing coping resources, and meeting unmet needs would be helpful to patients' adjustment to financial stress.

Whole-protein enteral nutrition formula supplementation reduces Escherichia and improves intestinal barrier function in HIV-infected immunological nonresponders.

People living with human immunodeficiency virus (PLWH) have persistent malnutrition, intestinal barrier dysfunction, and gut microbial imbalance. The interplay between gut microbiota and nutrients is involved in the immune reconstitution of PLWH. To evaluate the effects of whole-protein enteral nutrition formula supplementation on T-cell levels, intestinal barrier function, nutritional status, and gut microbiota composition in human immunodeficiency virus (HIV)-infected immunological nonresponders (INRs) who failed to normalize CD4+ T-cell counts, with a number <350 cells/µL, a pilot study was carried out in 13 HIV-infected INRs undergoing antiretroviral therapy who received a 3-month phase supplementation of 200 mL/200 kcal/45 g whole-protein enteral nutrition formula once daily. Our primary endpoint was increased CD4+ T-cell counts. Secondary outcome parameters were changes in intestinal barrier function, nutritional status, and gut microbiota composition. We showed that CD4+ T-cell counts of HIV-infected INRs increased significantly after the 3-month supplementation. Dietary supplementation for 3 months improved the intestinal barrier function and nutritional status of HIV-infected INRs. Furthermore, the enteral nutrition formula significantly decreased the relative abundance of Escherichia at the genus level and increased the alpha diversity of gut microbiota in HIV-infected INRs. The findings demonstrated that the whole-protein enteral nutrition formula aids in reducing Escherichia and improving intestinal barrier function in HIV-infected INRs. This study provides insight into the role of nutrients in the improvement of immune reconstitution in HIV-infected INRs. This study is registered in the Chinese Clinical Trial Registry (Document No. ChiCTR2000037839; http://www.chictr.org.cn/index.aspx).

Chatbot-interfaced and cognitive-affective barrier-driven messages to improve colposcopy adherence after abnormal Pap test results in underserved urban women: A feasibility pilot study.

Challenges in ensuring adherence to colposcopy and follow-up recommendations, particularly within underserved communities, hinder the delivery of appropriate care. Informed by our established evidence-based program, we sought to assess the feasibility and acceptability of a novel cognitive-affective intervention delivered through a Chatbot interface, aimed to enhance colposcopy adherence within an urban inner-city population. We developed the evidence-based intervention, CervixChat, to address comprehension of colposcopy's purpose, human papillomavirus (HPV) understanding, cancer-related fatalistic beliefs, procedural concerns, and disease progression, offered in both English and Spanish. Females aged 21-65, with colposcopy appointments at an urban OBGYN clinic, were invited to participate. Enrolled patients experienced real-time counseling messages tailored via a Chatbot-driven barriers assessment, dispatched via text one week before their scheduled colposcopy. Cognitive-affective measures were assessed at baseline and through a 1-month follow-up. Participants also engaged in a brief post-intervention satisfaction survey and interview to capture their acceptance and feedback on the intervention. The primary endpoints encompassed study adherence (CervixChat response rate and follow-up survey rate) and self-evaluated intervention acceptability, with predefined feasibility benchmarks of at least 70% adherence and 80% satisfaction. Among 48 eligible women scheduled for colposcopies, 27 (56.3%) agreed, consented, and completed baseline assessments. Participants had an average age of 34 years, with 14 (52%) identifying as non-Hispanic White. Of these, 21 (77.8%) engaged with the CervixChat intervention via mobile phones. Impressively, 26 participants (96.3%) attended their diagnostic colposcopy within the specified timeframe. Moreover, 22 (81.5%) completed the follow-up survey and a brief interview. Barriers assessment revealed notable encodings in the Affect and Values/Goals domains, highlighting concerns and understanding around HPV, as well as its impact on body image and sexual matters. Persistent and relatively high intrusive thoughts and lowered risk perceptions regarding cervical cancer were reported over time, unaffected by the intervention. Post-intervention evaluations documented high satisfaction and perceived usefulness, with recommendations for incorporating additional practical and educational content. Our findings underscore the robust satisfaction and practicality of the CervixChat intervention among a diverse underserved population. Moving forward, our next step involves evaluating the intervention's efficacy through a Sequential Multiple Assignment Randomized Trial (SMART) design. Enhanced by personalized health coaching, we aim to further bolster women's risk perception, address intrusive thoughts, and streamline resources to effectively improve colposcopy screening attendance.

Our study focused on helping underserved women, especially from ethnic minorities, with abnormal Pap test results. We aimed to break down barriers preventing them from seeking necessary follow-up care. Using Chatbot-facilitated text messages, we reached out to offer timely support. Starting with a warm text, we asked participants to share their thoughts on their abnormal Pap results. We then sent targeted messages addressing concerns about colposcopy, cervical health, emotions, appointment importance, and coping strategies. Participants engaged actively, finding value in the messages for information and encouragement. Their responses highlighted concerns about the test and emotional challenges. We also identified the need to address worries about human papillomavirus (HPV), body image, and discomfort during the test. In conclusion, our study showcased the feasibility and acceptability of using Chatbot messages to provide tailored support after abnormal Pap tests. By addressing unique concerns, we aimed to alleviate distress and enhance adherence to follow-up care for better cervical cancer screening outcomes.