bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salt intake across the hypertension care cascade in the Bangladeshi adult population: a nationally representative cross-sectional study
Authors: Monower Md Mostafa , Abid Shehab Uddin Al , Abrar Ahmad Khairul , Choudhury Sohel Reza 
Published: April 2024

ObjectivesThis study aimed to examine the distribution of daily salt intake across the hypertension care cascade and assess the proportional distribution of these care cascade categories across various salt consumption level.DesignA population-based national cross-sectional study.SettingsData from the Bangladesh STEPS 2018 survey were used, encompassing both urban and rural strata within all eight divisions. National estimates were generated from weighted data.ParticipantsA diverse population of 6754 men and women aged 18–69 years was included in the study.Outcome measuresDaily salt consumption was estimated using the spot urine sodium concentration following Tanaka equation. Distribution of salt intake among different categories of hypertension care cascade, including hypertensives, aware of hypertension status, on treatment and under control, was assessed.ResultsIndividuals with hypertension consume more salt on average (9.18 g/day, 95% CI 9.02 to 9.33) than those without hypertension (8.95 g/day, 95% CI 8.84 to 9.05) (p<0.02). No significant differences were found in salt intake when comparing aware versus unaware, treated versus untreated and controlled versus uncontrolled hypertension. In the overall population, 2.7% (95% CI 2.1% to 3.6%) of individuals without hypertension adhered to the recommended salt intake (<5 g/day) while 1.6% (95% CI 1.0% to 2.4%) with hypertension did so (p<0.03). Among individuals with hypertension, 2.4% (95% CI 1.4% to 4.0%) of those aware followed the guideline while only 0.8% (95% CI 0.4% to 1.9%) of those unaware adhered (p<0.03). Additionally, no significant differences were observed in adherence between the treated versus untreated and controlled versus uncontrolled hypertension.ConclusionsIndividuals with hypertension consume significantly more salt than those without, with no significant variations in salt intake based on aware, treated and controlled hypertension. Adhering to WHO salt intake guidelines aids better blood pressure management. By addressing salt consumption across hypertension care cascade, substantial progress can be made in better blood pressure control.
Protocol for evaluating the effects of the Reducing Cardiometabolic Diseases Risk dietary pattern in the Chinese population with dyslipidaemia: a single-centre, open-label, dietary intervention study
Authors: Wu Qi , Zhang Liyang , Cheng Cheng , Chen Xukun , Bian Shanshan , Huang Li , Li Tongtong , Li Zhenshu , Liu Huan , Yan Jing , Du Yue , Chen Yongjie , Zhang Meilin , Cao Lichun , Li Wen , Ma Fei , Huang Guowei 
Published: April 2024

IntroductionCardiometabolic disease (CMD) is the leading cause of mortality in China. A healthy diet plays an essential role in the occurrence and development of CMD. Although the Chinese heart-healthy diet is the first diet with cardiovascular benefits, a healthy dietary pattern that fits Chinese food culture that can effectively reduce the risk of CMD has not been found.Methods/designThe study is a single-centre, open-label, randomised controlled trial aimed at evaluating the effect of the Reducing Cardiometabolic Diseases Risk (RCMDR) dietary pattern in reducing the risk of CMDs in people with dyslipidaemia and providing a reference basis for constructing a dietary pattern suitable for the prevention of CMDs in the Chinese population. Participants are men and women aged 35–45 years with dyslipidaemia in Tianjin. The target sample size is 100. After the run-in period, the participants will be randomised to the RCMDR dietary pattern intervention group or the general health education control group with a 1:1 ratio. The intervention phases will last 12 weeks, with a dietary intervention of 5 working days per week for participants in the intervention group. The primary outcome variable is the cardiometabolic risk score. The secondary outcome variables are blood lipid, blood pressure, blood glucose, body composition indices, insulin resistance and 10-year risk of cardiovascular diseases.Ethics and disseminationThe study complies with the Measures for Ethical Review of Life Sciences and Medical Research Involving Human Beings and the Declaration of Helsinki. Signed informed consent will be obtained from all participants. The study has been approved by the Medical Ethics Committee of the Second Hospital of Tianjin Medical University (approval number: KY2023020). The results from the study will be disseminated through publications in a peer-reviewed journal.Trial registration numberChinese Clinical Trial Registry (ChiCTR2300072472).
Pyroptosis activates conventional type I dendritic cells to mediate the priming of highly functional anticancer T cells
Authors: Inkol Jordon M , Westerveld Michael J , Verburg Shayla G , Walsh Scott R , Morrison Jodi , Mossman Karen L , Worfolk Sarah M , Kallio Kaslyn LF , Phippen Noah J , Burchett Rebecca , Wan Yonghong , Bramson Jonathan , Workenhe Samuel T 
Published: April 2024

BackgroundInitiation of antitumor immunity is reliant on the stimulation of dendritic cells (DCs) to present tumor antigens to naïve T cells and generate effector T cells that can kill cancer cells. Induction of immunogenic cell death after certain types of cytotoxic anticancer therapies can stimulate T cell-mediated immunity. However, cytotoxic therapies simultaneously activate multiple types of cellular stress and programmed cell death; hence, it remains unknown what types of cancer cell death confer superior antitumor immunity.MethodsMurine cancer cells were engineered to activate apoptotic or pyroptotic cell death after Dox-induced expression of procell death proteins. Cell-free supernatants were collected to measure secreted danger signals, cytokines, and chemokines. Tumors were formed by transplanting engineered tumor cells to specifically activate apoptosis or pyroptosis in established tumors and the magnitude of immune response measured by flow cytometry. Tumor growth was measured using calipers to estimate end point tumor volumes for Kaplan-Meier survival analysis.ResultsWe demonstrated that, unlike apoptosis, pyroptosis induces an immunostimulatory secretome signature. In established tumors pyroptosis preferentially activated CD103+and XCR1+type I conventional DCs (cDC1) along with a higher magnitude and functionality of tumor-specific CD8+T cells and reduced number of regulatory T cells within the tumor. Depletion of cDC1 or CD4+and CD8+T cells ablated the antitumor response leaving mice susceptible to a tumor rechallenge.ConclusionOur study highlights that distinct types of cell death yield varying immunotherapeutic effect and selective activation of pyroptosis can be used to potentiate multiple aspects of the anticancer immunity cycle.
Combining CRISPR-Cas9 and TCR exchange to generate a safe and efficient cord blood-derived T cell product for pediatric relapsed AML
Authors: Lo Presti Vania , Meringa Angelo , Dunnebach Ester , van Velzen Alice , Moreira Aida Valera , Stam Ronald W , Kotecha Rishi S , Krippner-Heidenreich Anja , Heidenreich Olaf T , Plantinga Maud , Cornel Annelisa , Sebestyen Zsolt , Kuball Jurgen , van Til Niek P , Nierkens S 
Published: April 2024

BackgroundHematopoietic cell transplantation (HCT) is an effective treatment for pediatric patients with high-risk, refractory, or relapsed acute myeloid leukemia (AML). However, a large proportion of transplanted patients eventually die due to relapse. To improve overall survival, we propose a combined strategy based on cord blood (CB)-HCT with the application of AML-specific T cell receptor (TCR)-engineered T cell therapy derived from the same CB graft.MethodsWe produced CB-CD8+T cells expressing a recombinant TCR (rTCR) against Wilms tumor 1 (WT1) while lacking endogenous TCR (eTCR) expression to avoid mispairing and competition. CRISPR-Cas9 multiplexing was used to target the constant region of the endogenous TCRα (TRAC) and TCRβ (TRBC) chains. Next, an optimized method for lentiviral transduction was used to introduce recombinant WT1-TCR. The cytotoxic and migration capacity of the product was evaluated in coculture assays for both cell lines and primary pediatric AML blasts.ResultsThe gene editing and transduction procedures achieved high efficiency, with up to 95% of cells lacking eTCR and over 70% of T cells expressing rWT1-TCR. WT1-TCR-engineered T cells lacking the expression of their eTCR (eTCR−/−WT1-TCR) showed increased cell surface expression of the rTCR and production of cytotoxic cytokines, such as granzyme A and B, perforin, interferon-γ (IFNγ), and tumor necrosis factor-α (TNFα), on antigen recognition when compared with WT1-TCR-engineered T cells still expressing their eTCR (eTCR+/+WT1-TCR). CRISPR-Cas9 editing did not affect immunophenotypic characteristics or T cell activation and did not induce increased expression of inhibitory molecules. eTCR−/−WT1-TCR CD8+CB-T cells showed effective migratory and killing capacity in cocultures with neoplastic cell lines and primary AML blasts, but did not show toxicity toward healthy cells.ConclusionsIn summary, we show the feasibility of developing a potent CB-derived CD8+T cell product targeting WT1, providing an option for post-transplant allogeneic immune cell therapy or as an off-the-shelf product, to prevent relapse and improve the clinical outcome of children with AML.
Bohr–Sommerfeld quantization condition for self-adjoint Dirac operators
Authors: Yoshida Naoya 
Published: April 2024

We study the eigenvalue problem for a self-adjoint 1D Dirac operator. It is known that, near an energy level where the square of the potential makes a simple well, the eigenvalues are approximated by a Bohr–Sommerfeld type quantization rule. A remarkable difference from the Schrödinger case appears in the Maslov correction term. This fact was recently found by Hirota [Real eigenvalues of a non-self-adjoint perturbation of the self-adjoint Zakharov–Shabat operator, J. Math. Phys. 58 (2017) 102–108] under the analyticity condition of the potential using a complex WKB method. In this paper, we approach this problem with a microlocal technique focusing on the asymptotic behavior of the eigenfunction along the characteristic set to generalize the result to [Formula: see text] potentials.
Abstract CT079: The Pseudovax trial: A novel peptide vaccine targeting mutated GNAS for pseudomyxoma peritonei
Authors: Flatmark Kjersti , Torgunrud Annette , Karianne Fleten G. , Davidson Ben , Juel Hedvig V. , Mensali Nadia , Andersen Christin Lund , Inderberg Else Marit 
Published: April 2024

Abstract
Background: Pseudomyxoma peritonei (PMP) is a rare cancer originating from appendiceal mucinous tumors, which may spread to encompass the entire peritoneal cavity. Complete surgical removal and hyperthermic intraperitoneal chemotherapy cures approximately half of the patients, but patients with recurrent or non-resectable disease have no efficacious treatment options. These patients have a high unmet need for novel treatment options, and in the Pseudovax trial we will explore a novel therapeutic concept. A main molecular driver of PMP (in up to 90% of cases) is otherwise rare mutations in the GNAS oncogene, coding for the Gsα protein. We hypothesized that mutated Gsα would be a tumor neoantigen, and in T cells isolated from peripheral blood of PMP patients, a strong T cell proliferative response was observed. In the corresponding tumors, T cells with up-regulated immune checkpoint molecules PD-1 and TIGIT were detected.
Study hypotheses: Patients with GNAS-mutated PMP has a preexisting, attenuated immune response directed against mutated Gsα protein. Vaccination with mutated Gsα peptides can be combined with immune checkpoint inhibition (ICI) with acceptable toxicity. The vaccine will reactivate the immune response and ICI will restore measurable anticancer immunity in patients.
Study design: The Pseudovax trial is a small (10 patients) first-in-human, proof-of-concept, prospective, open label, phase I trial. Patients with recurrent or non-resectable PMP are eligible for inclusion. During a treatment period of 12 months, a mutated Gsα peptide vaccine + adjuvant (GM-CSF) will be administered as intradermal injections. After 12 weeks, treatment with ICI will be initiated. The primary endpoints are toxicity and circulating immune response against the vaccine, measured as increase in interferon-gamma production or proliferation of circulating vaccine-specific T cells compared to pre-vaccination baseline. Secondary endpoints are progression-free survival (abdominopelvic CT scans, blood levels of carcinoembryonic antigen (CEA) and/or detection of GNAS mutation by ctDNA analysis).
Citation Format: Kjersti Flatmark, Annette Torgunrud, Fleten G. Karianne, Ben Davidson, Hedvig V. Juel, Nadia Mensali, Christin Lund Andersen, Else Marit Inderberg. The Pseudovax trial: A novel peptide vaccine targeting mutated GNAS for pseudomyxoma peritonei [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT079.
Abstract CT083: A first-in-human phase 1/2a study of a novel anti-PAUF monoclonal antibody PBP1510 in patients with advanced/metastatic pancreatic cancer
Authors: Batlle Jaime Feliu , King Daniel A. , Kim Jamie , Pradhan Sumita , Park Yun-Yong , Mandakhalikar Kedar Diwakar , Loh Wei Qi 
Published: April 2024

Abstract
Background Pancreatic Adenocarcinoma Up-regulated Factor (PAUF) is a protein overexpressed in pancreatic cancer but not in non-cancerous tissues and plays an important role in carcinogenesis and metastasis. PBP1510 is a first-in-class, anti-PAUF humanized immunoglobulin G1 monoclonal antibody developed for treatment of pancreatic cancer. PBP1510 demonstrated promising pancreatic cancer growth inhibition efficacies in in vivo patient-derived xenograft studies and is being evaluated in humans for the first time in the ongoing PAUF-I study.
Methods PAUF-I (NCT05141149) is an open-label, multi-center, Phase 1/2a study in advanced/metastatic pancreatic cancer patients. Eligible patients must have a tumor that has progressed on standard chemotherapy, with at least 1 measurable lesion per RECIST v1.1 criteria, an ECOG performance status score of 0 or 1, a life expectancy of ≥ 3 months, and adequate baseline organ function to enroll. PBP1510 is administered as a 90-minute intravenous infusion in 28-day cycles and tumor assessments are performed every 8 weeks from the first dose.
Phase 1 uses a 3 + 3 dose-escalation design to assess the safety, tolerability, pharmacokinetics (PK), and immunogenicity of ascending doses of PBP1510 as a single agent or in combination with gemcitabine (Table 1). The observation period for dose-limiting toxicities (DLT) is 28 days. ORR and pre- and post-treatment PAUF levels in tumor tissue will be explored in the analyses. A recommended phase 2 dose (RP2D) will be selected based on PK, safety, and efficacy data from Phase 1. Phase 2a is the dose expansion phase which aims to evaluate the safety, tolerability, PK, immunogenicity, and efficacy of PBP1510 administered at RP2D in combination with gemcitabine.
As of January 2024, 6 patients have been enrolled. The 1M cohort (1 mg/kg) was completed without any report of DLT. Dose escalation is in progress and DLT evaluation is ongoing for the 2nd and 3rd patients in the 2M cohort.

TABLE 1: NAND Dose escalation and cohorts (Phase 1) Monotherapy Combination Cohort PBP1510 Dose (mg/kg) Gemcitabine Dose (mg/m2) Cohort PBP1510 Dose (mg/kg) Gemcitabine Dose (mg/m2) 1M 1 - 1C 1 1000 2M 3 - 2C 3 1000 3M 6 - 3C 6 1000 4M 10 - 4C 10 1000 5M 15 - 5C 15 1000
Citation Format: Jaime Feliu Batlle, Daniel A. King, Jamie Kim, Sumita Pradhan, Yun-Yong Park, Kedar Diwakar Mandakhalikar, Wei Qi Loh. A first-in-human phase 1/2a study of a novel anti-PAUF monoclonal antibody PBP1510 in patients with advanced/metastatic pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT083.
Abstract CT221: Belzutifan, a hypoxia-inducible factor-2α (HIF-2α) inhibitor, for von Hippel-Lindau (VHL) disease-associated neoplasms: Long-term results of the phase 2 LITESPARK-004 study
Authors: Srinivasan Ramaprasad , Iliopoulos Othon , Beckermann Kathryn E. , Narayan Vivek , Maughan Benjamin L. , Oudard Stephane , Else Tobias , Maranchie Jodi K. , Iversen Ane B. , Cornell Jerry , Perini Rodolfo F. , Liu Yanfang , Linehan W. Marston , Jonasch Eric 
Published: April 2024

Abstract
Introduction: Belzutifan is a first-in-class HIF-2α inhibitor approved for patients (pts) with VHL disease-associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas (HB), or pancreatic neuroendocrine tumors (pNET) not requiring immediate surgery based on initial results from the phase 2 LITESPARK-004 study (NCT03401788). We present results from pts with more than 4 years of follow-up from LITESPARK-004.
Methods: Adults with germline VHL alteration, ≥1 measurable nonmetastatic RCC tumor, no RCC tumor &gt;3 cm requiring immediate surgery, and no prior systemic anticancer therapy received oral belzutifan 120 mg once daily until disease progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate (ORR) in VHL-associated RCC per RECIST v1.1 by independent review. Secondary end points included ORR in CNS HB and pNET; duration of response (DOR), time to response (TTR), progression-free survival (PFS), and time to surgery (TTS) in RCC, CNS HB, and pNET; and safety.
Results: As of April 3, 2023, 36 of 61 pts (59%) were continuing treatment. Median follow-up was 49.9 mo (range, 48.2-58.1). Efficacy data are shown in the table. In the 4 years preceding belzutifan treatment, 46 pts (75%) underwent a total of 86 VHL-related tumor reduction procedures (surgery or radiation therapy). Since starting belzutifan, 16 pts (26%) underwent 18 tumor reduction procedures (RCC, n = 13; CNS HB, n = 3; retinal HB, n = 2). Safety profile remained unchanged with long-term follow-up.
Conclusions: With a median follow-up of more than 4 years, belzutifan continues to demonstrate clinically meaningful ORR and durable responses in VHL-associated RCC, CNS HBs, and pNET. Fewer tumor reduction procedures were observed after pts started belzutifan treatment. These results support belzutifan as a standard of care for this pt population.
Citation Format: Ramaprasad Srinivasan, Othon Iliopoulos, Kathryn E. Beckermann, Vivek Narayan, Benjamin L. Maughan, Stephane Oudard, Tobias Else, Jodi K. Maranchie, Ane B. Iversen, Jerry Cornell, Rodolfo F. Perini, Yanfang Liu, W. Marston Linehan, Eric Jonasch. Belzutifan, a hypoxia-inducible factor-2α (HIF-2α) inhibitor, for von Hippel-Lindau (VHL) disease-associated neoplasms: Long-term results of the phase 2 LITESPARK-004 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT221.
Abstract CT266: Initial efficacy of surufatinib plus sintilimab and IBI310 for patients with high-grade advanced-neuroendocrine neoplasm: A multicenter, single arm phase 2 stud
Authors: Zhang Panpan , Wang Yakun , Li Jie , Shen Lin , Lu Ming 
Published: April 2024

Abstract
Background: High-grade advanced-neuroendocrine neoplasm (HG-NEN) are more aggressive and have worse prognosis. Surufatinib (SUR, a selective VEGFRs; FGFR1; and CSF-1R inhibitor). Ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1) has been recommended for extrapulmonary and non-pancreatic NEC if the disease progresses following chemotherapy by the NCCN guidelines for neuroendocrine tumors. Preclinical and clinical studies have shown that SUR is a good partner of immune checkpoint inhibitors (ICIs). In this study, we present findings of SUR combined with Sintilimab (SIN, anti-PD-1) and IBI310 (IBI, anti-CTLA-4) for HG-NEN patients (pts). Methods: Pts with histologically confirmed HG-NENs who resistant or intolerant to standard treatment were included in the study. Enrolled pts received SUR (250 mg, qd, po, q3w) combined with SIN (200 mg, d1, i.v.gtt, q3w) and IBI (1 mg/kg, d1, i.v.gtt, q6w). The primary endpoint was ORR per RECIST 1.1. The second endpoints were PFS, DCR, safety and OS. Results: By Dec 29, 2023, 14 pts were enrolled and available for efficacy assessment. Median age, 53 yrs (range 22- 66); male, 71.4%; ECOG PS 1, 50%; GEP-NEN, 57.1%; NEC, 71.4%; Median ki-67 index, 65% (range 25%-90%); liver metastases, 57.1%. 85.7% pts received prior systemic therapy (50% 1L and 35.7% ≥2L). Confirmed ORR was 28.6% and DCR 76.8%. Median PFS was 4.15 months. Among 9 pts with ≤1 prior systemic regimens, confirmed ORR and DCR were 44.4% and 88.9%, respectively, with a median PFS of 4.5 months. Out of 14 pts, all experienced some form of treatment- emergent events (TEAEs), with only 3 participants (21.4%) reporting grade 3 TEAEs. These included manageable events like increased bilirubin, immune pancreatitis, gastric retention, and increased amylase, each with a 7.1% incidence. No grade 4 TEAEs or new safety signals occurred. Conclusion: Surufatinib combined with Sintilimab and IBI310 showed a potential antitumor activity and a tolerable safety profile, providing an additional treatment option for pts with high-grade NEN.
Citation Format: Panpan Zhang, Yakun Wang, Jie Li, Lin Shen, Ming Lu. Initial efficacy of surufatinib plus sintilimab and IBI310 for patients with high-grade advanced-neuroendocrine neoplasm: A multicenter, single arm phase 2 stud [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT266.