bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the integration of refugee health data into national health information systems in Jordan, Lebanon, and Uganda
Authors: Bou-Karroum Lama , Daher Najla , Jabbour Mathilda , Akhu-Zaheya Laila , Khater Wejdan , Alloubani Aladeen , Orach Christopher Garimoi , Komakech Henry , Bennett Sara , El-Jardali Fadi 
Published: August 2024

Abstract
Background
With the increasing number of protracted refugee crises globally, it is essential to ensure strong national health information systems (HIS) in displacement settings that include refugee-sensitive data and disaggregation by refugee status. This multi-country study aims to assess the degree of integration of refugee health data into national HIS in Jordan, Lebanon, and Uganda and identify the strengths and weaknesses of their national HIS in terms of collecting and reporting on refugee-related health indicators.

Methods
The study employs a comparative country analysis approach using a three-phase framework. The first phase involved reviewing 4120 indicators compiled from global health organizations, followed by a multi-stage refinement process, resulting in 45 indicators distributed across five themes. The second phase consisted of selecting relevant criteria from the literature, including data sources, annual reporting, disaggregation by refugee status, refugee population adjustments, accuracy, and consistency. The third phase involved assessing data availability and quality of the selected indicators against these criteria.

Results
Our analysis uncovered significant challenges in assessing the health status of refugees in Jordan, Lebanon, and Uganda, primarily stemming from limitations in the available health data and indicators. Specifically, we identified significant issues including incomplete local data collection with reliance on international data sources, fragmented data collection from various entities leading to discrepancies, and a lack of distinction between refugees and host populations in most indicators. These limitations hinder accurate comparisons and analyses. In light of these findings, a set of actionable recommendations was proposed to guide policymakers in the three countries to improve the integration of refugee health data into their national HIS ultimately enhancing refugees’ well-being and access to healthcare services.

Conclusion
The current status of refugee-related health data in Jordan, Lebanon, and Uganda indicates the need for improved data collection and reporting practices, disaggregation by refugee status and better integration of refugee health data into national HIS to capture the health status and needs of refugees in host countries. Key improvement strategies include establishing a centralized authority for consistent and efficient data management, fostering transparent and inclusive data governance, and strengthening workforce capacity to manage refugee health data effectively.
Role of CDK4 as prognostic biomarker in Soft Tissue Sarcoma and synergistic effect of its inhibition in dedifferentiated liposarcoma sequential treatment
Authors: Vanni Silvia , Miserocchi Giacomo , Gallo Graziana , Fausti Valentina , Gabellone Sofia , Liverani Chiara , Spadazzi Chiara , Cocchi Claudia , Calabrese Chiara , De Luca Giovanni , Bassi Massimo , Gessaroli Manlio , Tomasetti Nicola , Campobassi Angelo , Pieri Federica , Ercolani Giorgio , Cavaliere Davide , Gurrieri Lorena , Riva Nada , Recine Federica , Ibrahim Toni , Mercatali Laura , Jones Robin , De Vita Alessandro 
Published: August 2024

AbstractSoft tissue sarcomas represent an heterogeneous group of rare mesenchymal tumors comprising 1% of all solid malignancies. Among them, liposarcoma is one of the most common histotypes with atypical lipomatous tumor/well differentiated liposarcoma and dedifferentiated liposarcoma (ALT/WDLPS and DDLPS) as the major sub-entities. The unavailability of predictive, prognostic and druggable biomarkers makes the management of these lesions challenging. In recent years CDK4 and its inhibitors have emerged as potential agents for these lesions especially for ALT/WDLPS and DDLPS but the results are not conclusive and need to be elucidated. This study involved 21 ALT/WDLPS and DDLPS patients. Histological analyses of MDM2 and CDK4 were carried out. Moreover, a DDLPS patient-derived cancer model was established in vitro and in vivo assessing the efficacy of palbociclib in combination and sequential treatment. Finally, in silico analyses on CDK4 expression were carried out. The results showed a higher expression of CDK4 and MDM2 in DDLPS compared to ALT/WDLPS. Moreover, no correlation between MDM2 expression and CDK4 was observed. Next, in vitro analysis of CDK4 inhibitor palbociclib showed an antagonistic effect when combined to other chemotherapeutics, while it exhibited a significant synergy when administered in sequential schedule with lenvatinib. Next, in vivo analysis on DDLPS xenotransplanted embryos assessing the efficacy and safety profile of the in vitro tested schedules confirmed the observed data. This proof-of-concept study sheds light on the natural history of ALT/WDLPS and DDLPS and provides the rationale for the clinical applicability of sequential treatment with palbociclib in the management of DDLPS.
The next frontier in immunotherapy: potential and challenges of CAR-macrophages
Authors: Li Jing , Chen Ping , Ma Wenxue 
Published: August 2024

AbstractChimeric antigen receptor macrophage (CAR-MΦ) represents a significant advancement in immunotherapy, especially for treating solid tumors where traditional CAR-T therapies face limitations. CAR-MΦ offers a promising approach to target and eradicate tumor cells by utilizing macrophages’ phagocytic and antigen-presenting abilities. However, challenges such as the complex tumor microenvironment (TME), variability in antigen expression, and immune suppression limit their efficacy. This review addresses these issues, exploring mechanisms of CAR-MΦ action, optimal construct designs, and interactions within the TME. It also delves into the ex vivo manufacturing challenges of CAR-MΦ, discussing autologous and allogeneic sources and the importance of stringent quality control. The potential synergies of integrating CAR-MΦ with existing cancer therapies like checkpoint inhibitors and conventional chemotherapeutics are examined to highlight possible enhanced treatment outcomes. Furthermore, regulatory pathways for CAR-MΦ therapies are scrutinized alongside established protocols for CAR-T cells, identifying unique considerations essential for clinical trials and market approval. Proposed safety monitoring frameworks aim to manage potential adverse events, such as cytokine release syndrome, crucial for patient safety. Consolidating current research and clinical insights, this review seeks to refine CAR-MΦ therapeutic applications, overcome barriers, and suggest future research directions to transition CAR-MΦ therapies from experimental platforms to standard cancer care options.
Pharmacokinetic/Pharmacodynamic modelling of Saxagliptin and its active metabolite, 5-hydroxy Saxagliptin in rats with Type 2 Diabetes Mellitus
Authors: Wang Tianyan , Tao Ting , Liu Yi , Dong Jie , Ni Shanhong , Liu Yun , Li Yanli , Xu Ning , Sun Zengxian 
Published: August 2024

Abstract
Background and purposes
It is unclear whether the parent Saxagliptin (SAX) in vivo is the same as that in vitro, which is twice that of 5-hydroxy Saxagliptin (5-OH SAX). This study is to construct a Pharmacokinetic-Pharmacodynamic (PK-PD) link model to evaluate the genuine relationship between the concentration of parent SAX in vivo and the effect.

Methods
First, we established a reliable Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS/MS) method and DPP-4 inhibition ratio determination method. Then, the T2DM rats were randomly divided into four groups, intravenous injection of 5-OH SAX (0.5 mg/kg) and saline group, intragastric administration of SAX (10 mg/kg) and Sodium carboxymethyl cellulose (CMC-Na) group. Plasma samples were collected at different time points for subsequent testing. Finally, we used the measured concentrations and inhibition ratios to construct a PK-PD link model for 5-OH SAX and parent SAX.

Results
A two-compartment with additive model showed the pharmacokinetic process of SAX and 5-OH SAX, the concentration-effect relationship was represented by a sigmoidal Emax model and sigmoidal Emax with E0 model for SAX and 5-OH SAX, respectively. Fitting parameters showed SAX was rapidly absorbed after administration (Tmax=0.11 h, t1/2, ka=0.07 h), widely distributed in the body (V ≈ 20 L/kg), plasma exposure reached 3282.06 ng*h/mL, and the elimination half-life was 6.13 h. The maximum plasma dipeptidyl peptidase IV (DPP-4) inhibition ratio of parent SAX was 71.47%. According to the final fitting parameter EC50, EC50, 5−OH SAX=0.46EC50, SAX(parent), it was believed that the inhibitory effect of 5-OH SAX was about half of the parent SAX, which is consistent with the literature.

Conclusions
The PK-PD link model of the parent SAX established in this study can predict its pharmacokinetic process in T2DM rats and the strength of the inhibitory effect of DPP-4 based on non-clinical data.
Pooled analysis on characteristics of nausea and vomiting in patients receiving trastuzumab deruxtecan (T-DXd) in clinical studies.
Authors: Park Yeon Hee , Cortés Javier , Modi Shanu , Hurvitz Sara A. , Bianchini Giampaolo , Iwata Hiroji , Shitara Kohei , Siena Salvatore , Goto Yasushi , Ku Geoffrey Yuyat , Charles Powell Andrew , Swain Sandra M. , Arunachalam Meena , Janek Martin , Cheng Yingkai , Chu Changan , Verma Purnima , Mathias Elton , Karnoub Maha , Rugo Hope S. 
Published: August 2024

12118 Background: The efficacy and safety profile of T-DXd has been established in patients (pts) with various tumor types, and nausea and vomiting are the most common treatment-emergent adverse events (TEAEs). T-DXd study protocols were refined over time to recommend prophylaxis (eg, neurokinin or serotonin receptor antagonists and/or steroids) before T-DXd treatment, in line with antiemetic and institutional guidelines. We conducted a pooled, post hoc analysis capturing safety information across tumor types; we report results on nausea and vomiting. While this analysis was not designed to assess antiemetic effectiveness, it reveals the incidence of nausea and vomiting in clinical trials of T-DXd 5.4 mg/kg in more detail across a large dataset. Methods: 1449 pts treated with ≥1 dose of 5.4 mg/kg T-DXd (every 3 wks) were included from 7 phase 1-3 clinical trials in metastatic HER2+ and HER2-low breast cancer, HER2+ gastric cancer, and HER2-mutant non–small cell lung cancer (DESTINY-Breast01, -Breast02, -Breast03, -Breast04, -Lung01, -Lung02, and the first-in-human phase 1 study J101 in multiple tumor types; study enrollment starting 2015-2021). Regardless of antiemetic use (including prophylaxis), the incidence, severity, time to onset, and duration of nausea and vomiting TEAEs were assessed along with event outcomes. Results: Of 1449 pts receiving T-DXd 5.4 mg/kg (median [range] number of 3-wk treatment cycles: 13 [1-60]), 74.6% (n=1081) experienced nausea, and 41.6% (n=603) reported vomiting. Most pts had grade 1/2 nausea (41.2%/27.6%) and/or vomiting (26.2%/12.8%). Grade 3 TEAEs of nausea were reported in 5.8% of pts, with grade ≥3 TEAEs of vomiting observed in 2.6% of pts. By the data cutoff for each trial, 66.9% of pts with nausea and 87.6% with vomiting had their symptoms resolve. Most pts who experienced nausea and vomiting did so during the initial 21 days (cycle 1; n=879 [81.3%] and 336 [55.7%], respectively; 35.8% of all pts received antiemetic prophylaxis at cycle 1); both TEAEs declined notably in subsequent cycles. Rates of drug discontinuation, dose reduction, and drug interruption due to nausea and vomiting were generally low (Table). Conclusions: Most nausea and vomiting events were reported during the first 3 wks of treatment and resolved. Appropriate prophylaxis of nausea and vomiting is a key management strategy and allows pts to benefit from longer treatment durations with T-DXd. Ongoing studies are exploring the implementation and impact of prophylaxis for T-DXd–related emesis. Clinical trial information: NCT03248492 , NCT03523585 , NCT03529110 , NCT03734029 , NCT03505710 , NCT04644237 , NCT02564900 . [Table: see text]
Acute care and overall survival results of a randomized trial of a virtual health intervention during routine cancer treatment.
Authors: Daly Robert Michael , Bryl Karolina , Baser Raymond E , Green Angela , Hung Tony , Gillespie Erin F. , Panageas Katherine , Postow Michael A. , Mao Jun J. 
Published: August 2024

1503 Background: Despite rapid development of virtual health interventions, little is known of their impact on acute healthcare utilization and survival outcomes. This study aimed to evaluate the effectiveness of Integrative Medicine at Home (IM@Home), a virtual mind-body fitness program, on unplanned hospital admission and overall survival among patients undergoing systemic cancer treatment. Methods: We conducted a randomized clinical trial of IM@Home (choice of 23 weekly virtual live mind-body and fitness classes) compared with an enhanced usual care (EUC) control intervention consisting of asynchronous recordings (standard of care plus access to 17 pre-recorded online meditation resources) for patients with melanoma, thoracic, gynecological, or head/neck cancers on systemic treatment who reported moderate or greater fatigue. The study intervention lasted up to 12 weeks, and patients were followed thereafter for clinical events. Admission to a hospital over the study period was collected from patient-reported-outcomes and the electronic medical records and compared between arms. Overall survival was estimated using the Kaplan-Meier method. Results: Between October 2021 and March 2023,128 patients were randomized: (mean age 64 years) 109 (85.2%) were female, 106 (82.8 %) white, 10 (7.8%) Black, 7 (5.5%) Asian, and 118 (92.2%) non-Hispanic. 49 (38.3%) patients had thoracic, 44 (34.4%) gynecological, 25 (19.5%) head/neck, and 10 (7.8%) melanoma cancer. 58 (45.3%) were receiving chemotherapy, 45 (35.2%) immunotherapies, and 29 (22.7%) targeted therapies. Compared to EUC, patients in the IM@Home group were less likely to be hospitalized (4/64 [6.3%] vs. 12/63 [19.1%], p=0.038) and spent fewer days in the hospital (4.3 vs. 10.5 mean days per patient, p<0.001) during the 12-week study period. Overall survival results were assessed in Feb 2024 after a median follow up of 20.3 months. Median overall survival was 24.3 months in the EUC arm and was not reached in the IM@Home intervention arm (p=0.06). Conclusions: Participation in the virtual IM@Home program reduced unplanned hospitalizations and number of hospitalization days among patients with cancer receiving systemic treatment. Larger studies with longer follow-up are needed to confirm the effect of virtual supportive care on improving overall survival and reducing acute healthcare utilization. Clinical trial information: NCT05053230 .
Efficacy and safety of LM-108, an anti-CCR8 monoclonal antibody, in combination with an anti-PD-1 antibody in patients with gastric cancer: Results from phase 1/2 studies.
Authors: Gong Jifang , Liu Chang , Yao Jun , Xue Junli , Dai Jing , Ji Yinghua , Markman Ben , Hiong Alison , Yang Xiuli , Zhao Rusen , Zheng Yi , Li Qingshan , Wu Jun , Barve Minal A. , Ariyapperuma Mihitha Hashara , Richardson Gary Edward , Qin Xia , Qin Crystal Ying , Shen Lin 
Published: August 2024

2504 Background: Targeting tumor-infiltrating regulatory T cells (Tregs) is a potential approach to overcome immunotherapy resistance in the treatment of cancers. LM-108 is a novel Fc-optimized, anti-CCR8 monoclonal antibody that selectively depletes tumor-infiltrating Tregs. Here we report a pooled analysis of results from 3 phase 1/2 studies (NCT05199753; NCT05255484; NCT05518045) to evaluate the efficacy and safety of LM-108 in combination with anti-PD-1 therapy in patients with gastric cancer. Methods: Eligible patients with gastric cancer treated with LM-108 in combination with an anti-PD-1 antibody were included in the analysis. Patients received intravenous LM-108 at dose levels of 3 mg/kg Q2W, 6 mg/kg Q3W, or 10 mg/kg Q3W plus an anti-PD-1 antibody (intravenous pembrolizumab 200 mg Q3W or 400 mg Q6W or toripalimab 240 mg Q3W). The primary endpoint was investigator-assessed ORR per RECIST v1.1. The secondary endpoints included safety, other efficacy outcomes, and biomarkers analysis. Data cutoff date for the pooled analysis was December 25, 2023. Results: Forty-eight patients with gastric cancer (median age: 60.5 years; male: 72.9%) from China, USA, and Australia were treated ≥ 1 dose of LM-108 in combination with pembrolizumab or toripalimab. Most (n = 47, 97.9%) patients had received at least 1 prior anticancer treatment, and 43 (89.6%) had received prior anti-PD-1 therapy. Treatment-related adverse events (TRAEs) occurred in 39 (81.3%) patients, in which the most common events (≥15%) were alanine transaminase increased (25.0%), aspartate transaminase increased (22.9%), white blood cell decreased (22.9%), anemia (16.7%). Grade ≥ 3 TRAEs occurred in 18 (37.5%) patients, the most common events (≥ 4%) were anemia (8.3%), lipase increased (4.2%), rash (4.2%), and lymphocyte count decreased (4.2%). Among 36 efficacy-evaluable patients across all regimens, ORR was 36.1% (95% CI 20.8%–53.8%) and DCR was 72.2% (95% CI 54.8%–85.8%). The median PFS was 6.53 months (95% CI 2.96–NA). Among 11 patients whose disease had progressed on first-line treatment, ORR was 63.6% (95% CI 30.8%–89.1%) and DCR was 81.8% (95% CI 48.2%–97.7%). Of the 11 patients who progressed on first-line treatment, 8 had high CCR8 expression. Among these 8 patients, ORR was 87.5% and DCR was 100%, with 1 CR, 6 PR, and 1 SD observed. Conclusions: LM-108 in combination with an anti-PD-1 antibody showed promising antitumor activity in patients with gastric cancer that was resistance to anti-PD-1 therapy. The combination therapy was well tolerated. These results support further evaluation of LM-108 in CCR8 positive gastric cancer. Clinical trial information: NCT05199753 ; NCT05255484 ; NCT05518045 .
Early clues in the battle against advanced gastric cancer: How plasma ctDNA signals the effectiveness of PD-1 inhibitors with chemotherapy.
Authors: Jiang Rongqi , Wu Hao , Meng Enqing , Li Ping , Cheng Xu 
Published: August 2024

3042 Background: Combination therapy with Programmed Death 1 (PD-1) inhibitors and chemotherapy has shown efficacy in improving survival in advanced gastric cancer, but not all patients derive benefit. We aimed to explore whether early dynamic changes in circulating tumor DNA (ctDNA) can serve as predictors of treatment response and long-term survival in patients receiving first-line PD-1 inhibitors combined with chemotherapy. Methods: This is a prospective, single-center trial in which all patients are adults with advanced or metastatic GC/GEJC confirmed by pathology or imaging. 30 eligible patients will receive PD-1 mab (sintilimab/nivolumab (NIVO) Q3W) and chemotherapy (SOX/XELOX Q3W) regardless of programmed death ligand-1 status. Blood samples were collected before treatment and after two treatment cycles for ctDNA analysis. Plasma ctDNA was isolated for evaluating variant allele frequencies (VAF) of somatic mutations in 47 cancer-related genes using next-generation sequencing (NGS), ctDNA response was defined as clearance of maximum VAF (maxVAF) compared to baseline. CT scans were performed after every two cycles and will be categorized as responding (complete response plus partial response) or non-responding (progress disease plus stable disease) according to RECIST v1.1. Overall survival was calculated from the date of first PD-1 mab infusion to the time of death or censored at most recent follow-up; progression‐free survival was calculated from the date of first PD-1 mab infusion to the time of death or first documented progression, whichever came first, or censored at most recent follow-up. Results: In thirty advanced gastric cancer patients, the dynamic changes in maxVAF demonstrated a significant association with patients attaining either complete response (CR) or partial response (PR) to treatment (P=0.0021), but showed no correlation with stable disease (SD) or progress disease (PD). A substantial agreement was observed between ctDNA response and the best tumor shrinkage rate (Cohen's kappa=0.69). The objective response rate (ORR) among ctDNA responders was 85%, markedly higher compared to the 22% observed in non-responders (P=0.0073). Additionally, patients with ctDNA response had a significantly longer progression‐free survival (PFS) compared to patients without ctDNA response (median PFS 15.6 months vs 6.0 months; HR, 0.18; 95% CI, 0.06 to 0.61; p=0.003), overall survival (OS) was also significantly longer among ctDNA responders (median OS not reach[NR] vs 9.0 months; HR, 0.10; 95% CI, 0.01 to 0.88; p=0.011). Conclusions: ctDNA response serves as a potential biomarker for assessing treatment efficacy and long-term outcomes in advanced gastric cancer patients treated with first-line PD-1 inhibitors and chemotherapy. Clinical trial information: ChiCTR2200065366.
Efficacy and safety of fruquintinib plus investigator's choice of chemotherapy as second-line therapy in metastatic colorectal cancer: Updated results of a multicenter, single-arm, phase 2 trial.
Authors: Zhao Wensi , Li Jun , Li Liping , Huang Junping , Gong Wei , Yu Xiongjie , Le Kefa , He Linli , Han Qi , Wang Songlin , Tang Ze , Li Wenbin , Hua Xianliang , Chen Yongshun 
Published: August 2024

3571 Background: Fruquintinib, a potent and highly selective vascular endothelial growth factor receptor (VEGFR) inhibitor, combined with investigator’s choice of chemotherapy as second-line therapy in patients (pts) with metastatic colorectal cancer (mCRC) showed promising efficacy in preliminary analysis (2023 ASCO Poster-3582) of the prospective, open-label, multicenter, single-arm phase 2 trial (ChiCTR2200059280). Here we reported the updated efficacy data. Methods: Pts with mCRC progressed after first-line prior systemic treatment were administered fruquintinib (5~3 mg, d1-21, q4w) and investigator’s choice of chemotherapy (fluorouracil ± irinotecan ± oxaliplatin, d1, q3w) for up to 8 cycles. Patients without disease progression (PD) were followed by fruquintinib maintenance until PD or unacceptable toxicities. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), overall survival (OS) and safety. Results: From November 2021 to November 2023, 100 pts were enrolled. Median age was 63 years (IQR, 56.5-71) and 61.0% were male. The left colon cancer involved in 77.0% pts. All pts had MSS/pMMR phenotype and 37.0% had RAS/BRAF-mutated tumors. 9.0% received prior anti-EGFR and 55.0% received anti-VEGF therapy. Most common sites of metastatic disease were liver (57.0%) and lung (41.0%). As of January 20, 2024, with a median follow-up of 9.3 mo, the median PFS was 6.9 mo (95%CI, 5.2-8.6), median OS was 20.1 mo (95%CI, 13.7-26.3). ORR was 26.0% (95%CI, 17.9-36.2), DoR was 11.3 mo (95%CI, 8.6-14.0), and DCR was 83.3% (95%CI, 74.0-89.9) in 96 efficacy-evaluable pts. The incidence of adverse events was comparable to the known toxicities associated with fruquintinib and chemotherapy. No treatment-related deaths occurred. Grade 3/4 adverse effects occurred in 33 pts (33.0%), and most commonly were neutropenia (21.0%), leukopenia (14.0%), thrombocytopenia (6.0%), proteinuria (5.0%), hypothyroidism (3.0%), diarrhea (2.0%), hand-foot syndrome (2.0%) and hypertension (1.0%). Conclusions: Fruquintinib combined with investigator’s chemotherapy followed by fruquintinib maintenance as second-line therapy showed satisfactory anti-tumor activity, prolonged PFS and OS, and manageable safety profiles in pts with mCRC. Further analysis of all pts with long-term follow-up will be presented in the future. Clinical trial information: ChiCTR2200059280.