A multilevel intervention to promote HPV vaccination among young adults in Texas: protocol for a randomized controlled trial.

BACKGROUND: Human papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9, protects against HPV infection and can prevent HPV-associated invasive cancers. However, Gardasil-9 is one of the most underused vaccines in the US today. Young adults are at risk for HPV infection, but many are not vaccinated. This study uses a randomized controlled trial (RCT) to test an innovative multilevel intervention to increase HPV vaccination rates among young adults. In this paper, we describe the research protocol. METHODS: The study uses a two by three factorial design. A total of 1200 young adults in Texas, age 18-26 years, who have not been previously fully vaccinated against HPV will be randomly assigned to one of six conditions to receive: (1) standard CDC information about HPV vaccination (control); (2) video narratives about HPV vaccination; (3) written narratives about HPV vaccination; or (4-6) enhanced access to HPV vaccine combined with (4) standard CDC information, (5) video narratives, or (6) written narratives. The two primary outcomes are the rate of HPV vaccination initiation by 3-month follow-up and rate of HPV vaccination completion by 9-month follow-ups. We will determine the impact of the individual level intervention (i.e., persuasive narratives through video or written format), the systemic level intervention (i.e., enhanced access to HPV vaccines), and the combination of both levels, on HPV vaccination initiation and completion. We will also use purposive sampling to select participants to take part in semi-structured interviews/focus groups to better understand the mechanisms of the intervention. DISCUSSION: Recruitment and data collection began in March 2022. We expect to complete data collection by March 2026. We expect that narratives, enhanced access, and the combination of both will improve HPV vaccination initiation and completion rates among young adults. If proven successful, these individual- and system-level interventions can be easily disseminated in regions with low HPV vaccination rates to improve HPV vaccination, and ultimately decrease HPV-related cancer burden. TRIAL REGISTRATION: NCT05057312.

First-episode psychiatric disorder risk from SARS-CoV-2 infection, a clinical analysis with Chinese psychiatric inpatients.

The extensive spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout China in late 2022 has underscored the correlation between this virus and severe psychiatric disorders. Nevertheless, there remains a dearth of reported corresponding clinical and pathological features. Accordingly, we retrospectively reviewed the electronic medical records of psychiatric inpatients for seven days from early January 2023. Twenty-one inpatients who developed first-episode psychiatric disorders within two weeks after SARS-CoV-2 infection were recruited, while 24 uninfected the first-episode psychiatric inpatients were selected as controls. Comparative analyses of clinical manifestations, routine laboratory, and imaging examinations were performed. Our investigation revealed a 330% increase in first-episode psychiatric inpatients incidence after SARS-CoV-2 infection in 2023 compared to the preceding year without infections. Most cases exhibited psychiatric symptoms within a week of infection, resolving about two weeks with no residual symptoms after a three month. One-way ANOVA analysis between inpatients characterized by psychotic symptoms and hyperthermia was significant. Infected inpatients displayed elevated cytokine levels of interleukin-4, interleukin-8, and interferon-α, and decreased levels of eosinophils and basophils. These finding suggested that SARS-CoV-2 may contribute to the development of psychiatric disorders, likely mediated by the virus-induced inflammatory response and neuronal dysfunction in the context of psychological distress.

Collaborative Modeling to Compare Different Breast Cancer Screening Strategies: A Decision Analysis for the US Preventive Services Task Force.

Importance: The effects of breast cancer incidence changes and advances in screening and treatment on outcomes of different screening strategies are not well known. Objective: To estimate outcomes of various mammography screening strategies. Design, Setting, and Population: Comparison of outcomes using 6 Cancer Intervention and Surveillance Modeling Network (CISNET) models and national data on breast cancer incidence, mammography performance, treatment effects, and other-cause mortality in US women without previous cancer diagnoses. Exposures: Thirty-six screening strategies with varying start ages (40, 45, 50 years) and stop ages (74, 79 years) with digital mammography or digital breast tomosynthesis (DBT) annually, biennially, or a combination of intervals. Strategies were evaluated for all women and for Black women, assuming 100% screening adherence and "real-world" treatment. Main Outcomes and Measures: Estimated lifetime benefits (breast cancer deaths averted, percent reduction in breast cancer mortality, life-years gained), harms (false-positive recalls, benign biopsies, overdiagnosis), and number of mammograms per 1000 women. Results: Biennial screening with DBT starting at age 40, 45, or 50 years until age 74 years averted a median of 8.2, 7.5, or 6.7 breast cancer deaths per 1000 women screened, respectively, vs no screening. Biennial DBT screening at age 40 to 74 years (vs no screening) was associated with a 30.0% breast cancer mortality reduction, 1376 false-positive recalls, and 14 overdiagnosed cases per 1000 women screened. Digital mammography screening benefits were similar to those for DBT but had more false-positive recalls. Annual screening increased benefits but resulted in more false-positive recalls and overdiagnosed cases. Benefit-to-harm ratios of continuing screening until age 79 years were similar or superior to stopping at age 74. In all strategies, women with higher-than-average breast cancer risk, higher breast density, and lower comorbidity level experienced greater screening benefits than other groups. Annual screening of Black women from age 40 to 49 years with biennial screening thereafter reduced breast cancer mortality disparities while maintaining similar benefit-to-harm trade-offs as for all women. Conclusions: This modeling analysis suggests that biennial mammography screening starting at age 40 years reduces breast cancer mortality and increases life-years gained per mammogram. More intensive screening for women with greater risk of breast cancer diagnosis or death can maintain similar benefit-to-harm trade-offs and reduce mortality disparities.

Autism spectrum disorder diagnosis with EEG signals using time series maps of brain functional connectivity and a combined CNN-LSTM model.

BACKGROUND AND OBJECTIVE: People with autism spectrum disorder (ASD) often have cognitive impairments. Effective connectivity between different areas of the brain is essential for normal cognition. Electroencephalography (EEG) has been widely used in the detection of neurological diseases. Previous studies on detecting ASD with EEG data have focused on frequency-related features. Most of these studies have augmented data by splitting the dataset into time slices or sliding windows. However, such approaches to data augmentation may cause the testing data to be contaminated by the training data. To solve this problem, this study developed a novel method for detecting ASD with EEG data. METHODS: This study quantified the functional connectivity of the subject's brain from EEG signals and defined the individual to be the unit of analysis. Publicly available EEG data were gathered from 97 and 92 subjects with ASD and typical development (TD), respectively, while they were at rest or performing a task. Time-series maps of brain functional connectivity were constructed, and the data were augmented using a deep convolutional generative adversarial network. In addition, a combined network for ASD detection, based on convolutional neural network (CNN) and long short-term memory (LSTM), was designed and implemented. RESULTS: Based on functional connectivity, the network achieved classification accuracies of 81.08% and 74.55% on resting state and task state data, respectively. In addition, we found that the functional connectivity of ASD differed from TD primarily in the short-distance functional connectivity of the parietal and occipital lobes and in the distant connections from the right temporoparietal junction region to the left posterior temporal lobe. CONCLUSIONS: This paper provides a new perspective for better utilizing EEG to understand ASD. The method proposed in our study is expected to be a reliable tool to assist in the diagnosis of ASD.

Microstructure, Mechanical Property and Thermal Conductivity of Porous TiCO Ceramic Fabricated by In Situ Carbothermal Reduction of Phenolic Resin and Titania.

The porous TiCO ceramic was synthesized through a one-step sintering method, utilizing phenolic resin, TiO2 powder, and KCl foaming agent as raw materials. Ni(NO3)2·6H2O was incorporated as a catalyst to facilitate the carbothermal reaction between the pyrolytic carbon and TiO2 powder. The influence of Ni(NO3)2·6H2O catalyst content (0, 5, 10 wt.% of the TiO2 powder) on the microstructure, compressive strength, and thermal conductivity of the resultant porous TiCO ceramic was examined. X-ray diffraction and X-ray photoelectron spectroscopy results confirmed the formation of TiC and TiO in all samples, with an increase in the peak of TiC and a decrease in that of TiO as the Ni(NO3)2·6H2O content increased from 0% to 10%. Scanning electron microscopy results demonstrated a morphological change in the pore wall, transforming from a honeycomb-like porous structure composed of well-dispersed carbon and TiC-TiO particles to rod-shaped TiC whiskers, interconnected with each other as the catalyst content increased from 0% to 10%. Mercury intrusion porosimetry results proved a dual modal pore-size distribution of the samples, comprising nano-scale pores and micro-scale pores. The micro-scale pore size of the samples minorly changed, while the nano-scale pore size escalated from 52 nm to 138 nm as the catalyst content increased from 0 to 10%. The morphology of the pore wall and nano-scale pore size primarily influenced the compressive strength and thermal conductivity of the samples by affecting the load-bearing capability and solid heat-transfer conduction path, respectively.

Harnessing adenovirus in cancer immunotherapy: evoking cellular immunity and targeting delivery in cell-specific manner.

Recombinant adenovirus (rAd) regimens, including replication-competent oncolytic adenovirus (OAV) and replication-deficient adenovirus, have been identified as potential cancer therapeutics. OAV presents advantages such as selective replication, oncolytic efficacy, and tumor microenvironment (TME) remodeling. In this perspective, the principles and advancements in developing OAV toolkits are reviewed. The burgeoning rAd may dictate efficacy of conventional cancer therapies as well as cancer immunotherapies, including cancer vaccines, synergy with adoptive cell therapy (ACT), and TME reshaping. Concurrently, we explored the potential of rAd hitchhiking to adoptive immune cells or stem cells, highlighting how this approach facilitates synergistic interactions between rAd and cellular therapeutics at tumor sites. Results from preclinical and clinical trials in which immune and stem cells were infected with rAd have been used to address significant oncological challenges, such as postsurgical residual tumor tissue and metastatic tissue. Briefly, rAd can eradicate tumors through various mechanisms, resulting from tumor immunogenicity, reprogramming of the TME, enhancement of cellular immunity, and effective tumor targeting. In this context, we argue that rAd holds immense potential for enhancing cellular immunity and synergistically improving antitumor effects in combination with novel cancer immunotherapies.

Complete remission of advanced pancreatic cancer induced by claudin18.2-targeted CAR-T cell therapy: a case report.

Pancreatic cancer (PC) is one of the most malignant tumors in digestive system due to its highly invasive and metastatic properties. At present, conventional treatment strategies for PC show the limited clinical efficacy. Therefore, novel effective therapeutic strategies are urgently needed. Here, we report a case of complete remission of advanced PC induced by claudin18.2-targeted CAR-T cell therapy. The patient was a 72-year-old man who was diagnosed with pancreatic ductal adenocarcinoma 2 years ago, and he experienced tumor recurrence and multiple metastases after pancreaticoduodenectomy and multi-line chemotherapies, including liver, peritoneum, and cervical lymph node metastases. Then, the patient was referred to our department for further treatment of metastatic PC, and he was enrolled in a clinical trial of claudin18.2-targeted CAR-T cell therapy. After lymphodepleting chemotherapy, the patient received claudin18.2-targeted CAR-T cell infusion at a dose of 1.2 × 106 cells/kg on November 21, 2022. During CAR-T cell therapy, the patient experienced grade 2 cytokine release syndrome (CRS) and gastric mucosa injury, which were controlled by tocilizumab and conventional symptomatic and supportive treatment. The patient achieved a complete response (CR) 1 month after claudin18.2-targeted CAR-T cell therapy, and remained in clinical remission for 8 months. Unfortunately, the patient experienced claudin18.2-negative relapse in July, 2023. Despite antigen-negative relapse after claudin18.2-targeted CAR-T cell infusion, the patient achieved sustained remission for 8 months, which indicates that claudin18.2-targeted CAR-T cell therapy is an extremely effective therapeutic strategy for the treatment of advanced PC.

Dyadic Yoga for Head and Neck Cancer Patients Undergoing Chemoradiation and their Family Caregivers.

OBJECTIVES: Concurrent chemoradiation to treat head and neck cancer (HNC) may result in debilitating toxicities. Targeted exercise such as yoga therapy may buffer against treatment-related sequelae; thus, this pilot RCT examined the feasibility and preliminary efficacy of a yoga intervention. Because family caregivers report low caregiving efficacy and elevated levels of distress, we included them in this trial as active study participants. METHODS: HNC patients and their caregivers were randomized to a 15-session dyadic yoga program or a waitlist control (WLC) group. Prior to randomization, patients completed standard symptom (MDASI-HN) and patients and caregivers completed quality of life (SF-36) assessments. The 15-session program was delivered parallel to patients' treatment schedules. Participants were re-assessed at patients' last day of chemoradiation and again 30 days later. Patients' emergency department visits, unplanned hospital admissions and gastric feeding tube placements were recorded over the treatment course and up to 30 days later. RESULTS: With a consent rate of 76%, 37 dyads were randomized. Participants in the yoga group completed a mean of 12.5 sessions and rated the program as "beneficial." Patients in the yoga group had clinically significantly less symptom interference and HNC symptom severity and better QOL than those in the WLC group. They were also less likely to have a hospital admission (OR = 3.00), emergency department visit (OR = 2.14), and/or a feeding tube placement (OR = 1.78). CONCLUSION: Yoga therapy appears to be a feasible, acceptable, and possibly efficacious behavioral supportive care strategy for HNC patients undergoing chemoradiation. A larger efficacy trial is warranted.

Patients with advanced cancer and their spouses parenting minor children: The role of the relationship context in parenting concerns.

OBJECTIVE: Patients with advanced cancer who parent minor children report parenting concerns and increased psychological distress. This cross-sectional study seeks to understand parenting-related issues in patients and spousal caregivers from a relationship perspective. METHODS: Patients with a metastatic solid malignancy and their spouses independently completed cross-sectional assessments of psychological distress (Hospital Anxiety and Depression Scale), parenting concerns (Parenting Concern Questionnaire) and efficacy (Cancer-Related Parenting Self-Efficacy Scale), and relationship measures (DAS-7, Couples' Illness Communication Scale, and Family Relationship Index). RESULTS: Of the 51 patients (57% female, 49% NHW, mean age 42 years) and spouses (43% female, 43% NHW, mean age of 42 years), approximately 50% couples endorsed psychological distress and were at risk for family dysfunction. Spouses reported significantly higher levels of parenting-related concerns (t = -2.0, p < 0.05) and anxiety (t = -2.8, p < 0.001) than patients. Parenting concerns were significantly associated with illness communication (r = -0.56, p < 0.001) and family function (r = -0.38, p < 0.001). Although the expected interactions between parenting concerns and relationship variables (i.e., illness communication, dyadic adjustment, and family function) were significant for depressive symptoms at p < 0.05, the associations were not in the expected direction. Relationship function buffered against depressive symptoms for those with low rather than high parenting concerns. CONCLUSIONS: Not only patients but also spouses report cancer-related parenting concerns. The associations between parenting concerns and distress were stronger for spouses than patients. Dual caregiving appears to be a particularly stressful role. Because relationship function was associated with parenting concerns, we suggest that parent support programs that are couple-based and include both parenting-specific and relationship-specific content may be most effective in reducing distress for this vulnerable population.

Dietary Magnesium Replacement for Prevention of Hypomagnesemia in Patients With Ovarian Cancer Receiving Carboplatin-Based Chemotherapy.

PURPOSE: Hypomagnesemia is a common side effect of platinum-based chemotherapy and predicts poor overall survival in some cancers. Standard magnesium replacement strategies are often inadequate for maintaining magnesium levels. We hypothesized that a daily dietary magnesium replacement approach through magnesium-rich foods would help maintain adequate magnesium levels during platinum-based treatment. MATERIALS AND METHODS: We conducted a prospective feasibility study of magnesium-rich diets in patients 18 years and older with previously untreated ovarian cancer scheduled to receive carboplatin-containing chemotherapy of at least six consecutive cycles. Education about magnesium-rich diets was provided at enrollment and then weekly during chemotherapy. Feasibility was defined as ≥60% completion of dietary recalls and ≥280 mg average daily dietary magnesium intake across all patients. RESULTS: Twenty-one of 26 patients enrolled completed at least five chemotherapy cycles and were included in the analysis. Adherence to the study diet was 76%. Daily dietary magnesium intake was 100.5 mg at baseline and increased throughout each cycle: 6% of patients at baseline, 24% after the first cycle, and 67% after the fifth cycle reached ≥280-mg/day magnesium intake. Seven (33%) of 21 had at least one incident of hypomagnesemia. Patients who were adherent had significantly lower incidence of hypomagnesemia (19% v 80%, P = .03) and less need for intravenous magnesium (6% v 60%, P = .03) than those who were nonadherent. CONCLUSION: The study achieved primary feasibility objectives of retention and adherence to the study intervention. Weekly education about magnesium-rich diets was effective in increasing dietary magnesium intake. Adequate dietary magnesium appeared to be protective against hypomagnesemia.

Oral Toxicities Associated with Immune Checkpoint Inhibitors: Meta-Analyses of Clinical Trials.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, their oral toxicity profile is not well elucidated. This review aimed to investigate the prevalence of oral toxicities including xerostomia, mucositis/stomatitis, dysgeusia, dysphagia, oral/oropharyngeal pain, oral infections, angular cheilitis, osteonecrosis, osteomyelitis, and oral mucosal reactions with ICIs. A review protocol was registered with PROSPERO (ID: CRD42023391674). A systematic search of ClinicalTrials.gov was conducted as of April 10, 2022. Studies were selected, assessed, and data extracted using PRISMA guidelines. Oral toxicity data were extracted from study arms using a single immunotherapy drug. Meta-analyses were conducted to summarize prevalence of oral toxicities using random-effects models. Of 750 screened records, 95 trials were included in the meta-analysis with published results. Time between study completion and first publication on ClinicalTrials.gov was 1 to 146 months (mean = 20.3, SD = 18.4). Weighted pooled prevalence was 5% (95% CI: 4-6%) for xerostomia, 3% (95% CI: 3-4%) for mucositis/stomatitis, 3% (95% CI: 2-3%) for dysgeusia, 2% (95% CI: 1-2%) for dysphagia, 3% (95% CI: 2-4%) for oropharyngeal/oral pain, 2% (95% CI: 1-3%) for oral candidiasis, and 2% (95% CI: 0-4%) for angular cheilitis. Subgroup differences based on ICI drugs were minimal. No trials reported lichenoid or pemphigoid mucosal reactions. Meta-analysis results revealed low prevalence of oral toxicities with ICIs; however, data reporting was limited and inconsistent. Limitations of study dataset reveal a significant need for systematic collection of oral morbidity data as well as improved consistency and compliance of reporting results on ClinicalTrials.gov.

Analysis of Breast Cancer Mortality in the US-1975 to 2019.

Importance: Breast cancer mortality in the US declined between 1975 and 2019. The association of changes in metastatic breast cancer treatment with improved breast cancer mortality is unclear. Objective: To simulate the relative associations of breast cancer screening, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer with improved breast cancer mortality. Design, Setting, and Participants: Using aggregated observational and clinical trial data on the dissemination and effects of screening and treatment, 4 Cancer Intervention and Surveillance Modeling Network (CISNET) models simulated US breast cancer mortality rates. Death due to breast cancer, overall and by estrogen receptor and ERBB2 (formerly HER2) status, among women aged 30 to 79 years in the US from 1975 to 2019 was simulated. Exposures: Screening mammography, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer. Main Outcomes and Measures: Model-estimated age-adjusted breast cancer mortality rate associated with screening, stage I to III treatment, and metastatic treatment relative to the absence of these exposures was assessed, as was model-estimated median survival after breast cancer metastatic recurrence. Results: The breast cancer mortality rate in the US (age adjusted) was 48/100 000 women in 1975 and 27/100 000 women in 2019. In 2019, the combination of screening, stage I to III treatment, and metastatic treatment was associated with a 58% reduction (model range, 55%-61%) in breast cancer mortality. Of this reduction, 29% (model range, 19%-33%) was associated with treatment of metastatic breast cancer, 47% (model range, 35%-60%) with treatment of stage I to III breast cancer, and 25% (model range, 21%-33%) with mammography screening. Based on simulations, the greatest change in survival after metastatic recurrence occurred between 2000 and 2019, from 1.9 years (model range, 1.0-2.7 years) to 3.2 years (model range, 2.0-4.9 years). Median survival for estrogen receptor (ER)-positive/ERBB2-positive breast cancer improved by 2.5 years (model range, 2.0-3.4 years), whereas median survival for ER-/ERBB2- breast cancer improved by 0.5 years (model range, 0.3-0.8 years). Conclusions and Relevance: According to 4 simulation models, breast cancer screening and treatment in 2019 were associated with a 58% reduction in US breast cancer mortality compared with interventions in 1975. Simulations suggested that treatment for stage I to III breast cancer was associated with approximately 47% of the mortality reduction, whereas treatment for metastatic breast cancer was associated with 29% of the reduction and screening with 25% of the reduction.

DNA methylation landscape reveals GNAS as a decitabine-responsive marker in patients with acute myeloid leukemia.

BACKGROUND: The demethylation agent decitabine (DAC) is a pivotal non-intensive alternative treatment for acute myeloid leukemia (AML). However, patient responses to DAC are highly variable, and predictive biomarkers are warranted. Herein, the DNA methylation landscape of patients treated with a DAC-based combination regimen was compared with that of patients treated with standard chemotherapy to develop a molecular approach for predicting clinical response to DAC. METHODS: Twenty-five non-M3 AML patients were enrolled and subjected to DNA methylation sequencing and profiling to identify differentially methylated regions (DMRs) and genes of interest. Moreover, the effects of a DAC-based regimen on apoptosis and gene expression were explored using Kasumi-1 and K562 cells. RESULTS: Overall, we identified 541 DMRs that were specifically responsive to DAC, among which 172 DMRs showed hypomethylation patterns upon treatment and were aligned with the promoter regions of 182 genes. In particular, GNAS was identified as a critical DAC-responsive gene, with in vitro GNAS downregulation leading to reduced cell apoptosis induced by DAC and cytarabine combo treatment. CONCLUSIONS: We found that GNAS is a DAC-sensitive gene in AML and may serve as a prognostic biomarker to assess the responsiveness of patients with AML to DAC-based therapy.

An extended Bayesian semi-mechanistic dose-finding design for phase I oncology trials using pharmacokinetic and pharmacodynamic information.

We propose a model-based, semi-mechanistic dose-finding (SDF) design for phase I oncology trials that incorporates pharmacokinetic/pharmacodynamic (PK/PD) information when modeling the dose-toxicity relationship. This design is motivated by a phase Ib/II clinical trial of anti-CD20/CD3 T cell therapy in non-Hodgkin lymphoma patients; it extends a recently proposed SDF model framework by incorporating measurements of a PD biomarker relevant to the primary dose-limiting toxicity (DLT). We propose joint Bayesian modeling of the PK, PD, and DLT outcomes. Our extensive simulation studies show that on average the proposed design outperforms some common phase I trial designs, including modified toxicity probability interval (mTPI) and Bayesian optimal interval (BOIN) designs, the continual reassessment method (CRM), as well as an SDF design assuming a latent PD biomarker (SDF-woPD), in terms of the percentage of correct selection of maximum tolerated dose (MTD) and average number of patients allocated to MTD, under a variety of dose-toxicity scenarios. When the working PK model and the class of link function between the cumulative PD effect and DLT probability is correctly specified, the proposed design also yields better estimated dose-toxicity curves than CRM and SDF-woPD. Our sensitivity analyses suggest that the design's performance is reasonably robust to prior specification for the parameter in the link function, as well as misspecification of the PK model and class of the link function.

Favorable response of a patient with primary B/myeloid mixed phenotype acute Leukemia to CD19-CAR-T: Case report and literature review.

RATIONALE: Mixed phenotype acute leukemia (MPAL) is a rare and heterogeneous type of leukemia known for its poor prognosis. The optimal treatment strategy for this condition currently lacks consensus, leaving uncertainty in its management. Nonetheless, a potential therapeutic option for patients with refractory MPAL who express target antigens is donor-derived chimeric antigen receptor T (CAR-T) cell therapy. PATIENT CONCERNS: We recently reported a 61-year-old woman with MPAL and elucidated its diagnosis and treatment. DIAGNOSIS: The diagnosis of MPAL was established based on the classification of World Health Organization in 2016. INTERVENTIONS: Despite undergoing 3 different acute lymphoblastic leukemia (ALL) regimens and 1 acute myelogenous leukemia (AML) regimen, the patient did not achieve remission. Subsequently, the patient received human CD19-targeted CAR-T cell therapy. OUTCOMES: The patient achieved a successful and complete remission after CAR-T cell therapy. Tragically, 8 months after CAR-T infusion, the patient experienced a relapse characterized by CD19-negative disease and ultimately passed away. LESSONS: This case underscores the potential efficacy and safety of human-derived CD19 CAR-T cell therapy in treating refractory MPAL. While this particular patient outcome was unfortunate, it suggests that CAR-T cell therapy may still hold promise as a viable treatment option for MPAL patients unresponsive to other therapies. Further research in this field is warranted to determine the most effective treatment strategies for managing this challenging disease.

Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.

PURPOSE: Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. PATIENTS AND METHODS: To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. RESULTS: We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. CONCLUSIONS: Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.

Supportive Care for Dual Caregivers who Care for Their Partner With Cancer and Their Young Children.

PURPOSE: Advanced cancer patients and their spouses who parent minor children report parenting concerns and increased psychological distress. This single-arm trial examined the feasibility and initial evidence for efficacy of a novel parent support program. METHODS: Patients with a metastatic solid malignancy and their spouses completed self-reported assessments of psychological distress (HADS), parenting concerns (PCQ) and efficacy (CaPSE) at baseline. Both patients and spouses jointly attended the first two sessions addressing illness communication and family routines. Spouses individually attended two additional sessions focusing on caregiver support and death preparedness. All four sessions were delivered via videoconference by a licensed psychological counselor. Dyads completed program evaluations and were reassessed six and 12 weeks postintervention. RESULTS: With a consent rate of 61%, 10 patients (50% female; 90% non-Hispanic White; mean age = 42 years) and their spouses (50% female; 70% non-Hispanic White; mean age = 42 years) completed the assessments. All patients and 90% of spouses attended all intervention sessions and evaluated the program favorably. Paired t-tests revealed significant improvements in patients' parenting concerns at the six weeks (P = 0.003) and parenting efficacy at the six weeks (P = 0.03) and 12 weeks (P = 0.03) follow-ups. For spouses, we found significant improvements in parenting efficacy (P < 0.001) and depressive symptoms (P = 0.04) at six weeks and parenting concerns at both six weeks (P = 0.006) and 12 weeks (P = 0.001) follow-ups. CONCLUSIONS: The initial testing of our parenting intervention yielded promising results regarding feasibility and an initial signal of intervention efficacy. Thus, a randomized controlled trial for further testing is warranted.

Accurate transcriptome-wide identification and quantification of alternative polyadenylation from RNA-seq data with APAIQ.

Alternative polyadenylation (APA) enables a gene to generate multiple transcripts with different 3' ends, which is dynamic across different cell types or conditions. Many computational methods have been developed to characterize sample-specific APA using the corresponding RNA-seq data, but suffered from high error rate on both polyadenylation site (PAS) identification and quantification of PAS usage (PAU), and bias toward 3' untranslated regions. Here we developed a tool for APA identification and quantification (APAIQ) from RNA-seq data, which can accurately identify PAS and quantify PAU in a transcriptome-wide manner. Using 3' end-seq data as the benchmark, we showed that APAIQ outperforms current methods on PAS identification and PAU quantification, including DaPars2, Aptardi, mountainClimber, SANPolyA, and QAPA. Finally, applying APAIQ on 421 RNA-seq samples from liver cancer patients, we identified >540 tumor-associated APA events and experimentally validated two intronic polyadenylation candidates, demonstrating its capacity to unveil cancer-related APA with a large-scale RNA-seq data set.

Efficacy of a Smoking Cessation Intervention for Survivors of Cervical Intraepithelial Neoplasia or Cervical Cancer: A Randomized Controlled Trial.

PURPOSE: Women who smoke and have a history of cervical intraepithelial neoplasia (CIN) or cervical cancer represent a vulnerable subgroup at elevated risk for recurrence, poorer cancer treatment outcomes, and decreased quality of life. The purpose of this study was to evaluate the long-term efficacy of Motivation And Problem Solving (MAPS), a novel treatment well-suited to meeting the smoking cessation needs of this population. METHODS: Women who were with a history of CIN or cervical cancer, age 18 years and older, spoke English or Spanish, and reported current smoking (≥100 lifetime cigarettes plus any smoking in the past 30 days) were eligible. Participants (N = 202) were recruited in clinic in Oklahoma City and online nationally and randomly assigned to (1) standard treatment (ST) or (2) MAPS. ST consisted of repeated referrals to a tobacco cessation quitline, self-help materials, and combination nicotine replacement therapy (patch plus lozenge). MAPS comprised all ST components plus up to six proactive telephone counseling sessions over 12 months. Logistic regression and generalized estimating equations evaluated the intervention. The primary outcome was self-reported 7-day point prevalence abstinence from tobacco at 18 months, with abstinence at 3, 6, and 12 months and biochemically confirmed abstinence as secondary outcomes. RESULTS: There was no significant effect for MAPS over ST at 18 months (14.2% v 12.9%, P = .79). However, there was a significant condition × assessment interaction (P = .015). Follow-up analyses found that MAPS (v ST) abstinence rates were significantly greater at 12 months (26.4% v 11.9%, P = .017; estimated OR, 2.60; 95% CI, 1.19 to 5.89). CONCLUSION: MAPS led to a greater than two-fold increase in smoking abstinence among survivors of CIN and cervical cancer at 12 months. At 18 months, abstinence in MAPS declined to match the control condition and the treatment effect was no longer significant.