bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Study of ROR1-Specific CAR-T Cells in Advanced Hematopoietic and Epithelial Malignancies
Authors: Jaeger-Ruckstuhl Carla A. , Specht Jennifer M. , Voutsinas Jenna M. , MacMillan Hugh R. , Wu Qian (Vicky) , Muhunthan Vishaka , Berger Carolina , Pullarkat Shalini , Wright Jocelyn H. , Yeung Cecilia C.S. , Hyun Teresa S. , Seaton Brandon , Aicher Lauri D. , Song Xiaoling , Pierce Robert H. , Lo Yun , Cole Gabriel O. , Lee Sylvia M. , Newell Evan W. , Maloney David G. , Riddell Stanley R. 
Published: October 2024

Abstract

Purpose:
The receptor tyrosine kinase–like orphan receptor 1 (ROR1) is expressed in hematopoietic and epithelial cancers but has limited expression on normal adult tissues. This phase I study evaluated the safety of targeting ROR1 with autologous T lymphocytes engineered to express a ROR1 chimeric antigen receptor (CAR). Secondary objectives evaluated the persistence, trafficking, and antitumor activity of CAR-T cells.

Patients and Methods:
Twenty-one patients with ROR1+ tumors received CAR-T cells at one of four dose levels: 3.3 × 105, 1 × 106, 3.3 × 106, and 1 × 107 cells/kg body weight, administered after lymphodepletion with cyclophosphamide/fludarabine or oxaliplatin/cyclophosphamide. Cohort A included patients with chronic lymphocytic leukemia (CLL, n = 3); cohort B included patients with triple-negative breast cancer (TNBC, n = 10) or non–small cell lung cancer (NSCLC, n = 8). A second infusion was administered to one patient in cohort A with residual CLL in the marrow and three patients in cohort B with stable disease after first infusion.

Results:
Treatment was well tolerated, apart from one dose-limiting toxicity at dose level 4 in a patient with advanced NSCLC. Two of the three (67%) patients with CLL showed robust CAR-T–cell expansion and a rapid antitumor response. In patients with NSCLC and TNBC, CAR-T cells expanded to variable levels and infiltrated tumors poorly and 1 of 18 patients (5.5%) achieved partial response by RECIST 1.1.

Conclusions:
ROR1 CAR-T cells were well tolerated in most patients. Antitumor activity was observed in CLL but was limited in TNBC and NSCLC. Immunogenicity of the CAR and lack of sustained tumor infiltration were identified as limitations.
See related commentary by Kobold, p. 437
Update on Surveillance Guidelines in Emerging Wilms Tumor Predisposition Syndromes
Authors: Brzezinski Jack J. , Becktell Kerri D. , Bougeard Gaëlle , Brodeur Garrett M. , Diller Lisa R. , Doria Andrea S. , Hansford Jordan R. , Kohlmann Wendy K. , Kratz Christian P. , MacFarland Suzanne P. , Pajtler Kristian W. , Rednam Surya P. , Schienda Jaclyn , States Lisa J. , Villani Anita , Weksberg Rosanna , Zelley Kristin , Tomlinson Gail E. , Kalish Jennifer M. 
Published: October 2024

Abstract
Wilms tumors are commonly associated with predisposition syndromes. Many of these syndromes are associated with specific phenotypic features and are discussed in the related article from the AACR Pediatric Cancer Working Group. Guidelines for surveillance in this population were published in 2017, but since then several studies have identified new genes with recurrent pathogenic variants associated with increased risk for Wilms tumor development. In general, variants in these genes are less likely to be associated with other phenotypic features. Recently, members of the AACR Pediatric Cancer Working Group met to update surveillance guidelines for patients with a predisposition to Wilms tumors with a review of recently published evidence and risk estimates. Risk estimates for Wilms tumor for the more recently described genes are discussed here along with suggested surveillance guidelines for these populations. Several other emerging clinical scenarios associated with Wilms tumor predisposition are also discussed, including patients with family histories of Wilms tumor and no identified causative gene, patients with bilateral tumors, and patients with somatic mosaicism for chromosome 11p15.5 alterations. This perspective serves to update pediatric oncologists, geneticists, radiologists, counselors, and other health care professionals on emerging evidence and harmonize updated surveillance recommendations in the North American and Australian context for patients with emerging forms of Wilms tumor predisposition.
Mathematical Modeling Unveils Optimization Strategies for Targeted Radionuclide Therapy of Blood Cancers
Authors: Kuznetsov Maxim , Adhikarla Vikram , Caserta Enrico , Wang Xiuli , Shively John E. , Pichiorri Flavia , Rockne Russell C. 
Published: October 2024

Abstract
Targeted radionuclide therapy (TRT) is based on injections of cancer-specific molecules conjugated with radioactive nuclides. Despite the specificity of this treatment, it is not devoid of side effects limiting its use and is especially harmful for rapidly proliferating organs well perfused by blood, like bone marrow. Optimization of radioconjugate administration accounting for toxicity constraints can increase treatment efficacy. Based on our experiments on a disseminated multiple myeloma mouse model treated by 225Ac-DOTA-daratumumab, we developed a mathematical model, investigation of which highlighted the following principles for optimization of TRT: (i) Nuclide-to-antibody ratio importance. The density of radioconjugates on cancer cells determines the density of radiation energy deposited in them. A low labeling ratio as well as accumulation of unlabeled antibodies and antibodies attached to decay products in the bloodstream can mitigate cancer radiation damage due to excessive occupation of specific receptors by antibodies devoid of radioactive nuclides. (ii) Cancer-binding capacity–based dosing. The total number of specific receptors on cancer cells is a critical factor for treatment optimization, and its estimation may allow increasing treatment efficacy close to its theoretical limit. Injection of doses significantly exceeding cancer-binding capacity should be avoided because radioconjugates remaining in the bloodstream have a negligible efficacy-to-toxicity ratio. (iii) Particle range–guided multi-dosing. The use of short-range particle emitters and high-affinity antibodies can allow for robust treatment optimization via initial saturation of cancer-binding capacity, enabling redistribution of further injected radioconjugates and deposited doses toward still viable cells that continue expressing specific receptors.

Significance:
Mathematical modeling yields general principles for optimization of TRT in mouse models of multiple myeloma that can be extrapolated to other cancer models and clinical settings.
Neural Synchrony of Minds and Machines: Hippocampal Mechanisms to Advance AI and Virtual Networks
Authors: Sariñana Joshua 
Published: October 2024

Abstract
Artificial intelligence (AI) predicts behavior by learning from user data collected through digitally mediated interfaces. Virtual spaces---such as online social networks---extend the physical world into virtual worlds, leveraging AI technologies to transform user behavior into digital assets by mimicking the brain’s reinforcement networks. Social media platforms utilize AI to manipulate user behavior through rewards that can diverge from the user’s intended goals. This misalignment fragments user behavior and cognition, resulting in virtual disembodiment. Presented is a conceptual mechanism based on the hippocampus to synchronize AI and the brain, synthesizing the user’s physical and mental presence in virtual spaces.
Cold Season Cloud Response to Sea Ice Loss in the Arctic
Authors: Liu Yinghui , Key Jeffrey R. 
Published: October 2024

Abstract
Based on satellite observations, we investigate the cloud responses during the cold season, from October to the following March, to interannual fluctuations in Arctic sea ice concentrations during September and October. It is found that the cloud responses differ between the periods 2000–18 and 1982–99. From 2000 to 2018, increased Arctic Ocean cloud cover in October and November transitioned to significantly less cloud cover and cloud radiative forcing (CRF), from January to March, in response to lower sea ice concentrations in September and October. The lower CRF from January to March preconditions the sea ice and likely contributes to higher sea ice concentrations the following September. This suggests a negative cloud feedback on sea ice concentration, which may contribute to sea ice recovery after a dramatic decrease. In contrast, from 1982 to 1999, generally increased cloud cover and cloud radiative forcing persisted from October to March following lower sea ice concentrations in the preceding September and October. The cause of the different cloud responses to sea ice changes in these two time periods remains unclear and requires further investigation.
Wavelet-Entropy Enhanced Clustering: A Comprehensive Analysis of Drought Patterns in the Southern Plains, United States
Authors: Lee Sanghyun , Nourani Vahid , Danandeh Mehr Ali , Moriasi Daniel , Mirchi Ali 
Published: October 2024

Abstract
Droughts may exhibit spatiotemporal heterogeneity at a regional scale. Effective drought assessment and management necessitates identifying homogeneous areas. However, previous studies often simplified clustering analysis by focusing only on a single variable. In this study, we present a novel drought clustering map for the southern plains (SP) region of the United States by integrating the wavelet-entropy approach with k-means clustering algorithm to capture spatiotemporal patterns of drought-related variables across various resolutions while eliminating redundant information. We considered multiple drought indicators and indices including gridded precipitation (P), potential evapotranspiration (PET), normalized difference vegetation index (NDVI), and standardized precipitation evapotranspiration index (SPEI) as well as geographical coordinates and topography map. Through evaluating five different combinations of input datasets, we selected the one demonstrating optimal results based on the Davies–Bouldin and Calinski–Harabasz criteria. In addition to P, PET, and NDVI, including the coordinates and elevation as secondary variables significantly enhanced the clustering performance. Using these variables, the region was subdivided into 21 clusters. Pearson’s correlation coefficients for the SPEI between centroid members and corresponding cells within clusters averaged between 0.84 and 0.94. Comparison with an existing cluster map [Drought Risk Atlas (DRA)] for the region revealed that our proposed cluster map showed higher variability between clusters for P, PET, and NDVI, confirming the robustness of the clustering results for drought conditions in the SP. The new clustering framework is expected to provide valuable insights for understanding and addressing drought dynamics in the SP region.
Effects of training on Feline Grimace Scale scoring for acute pain assessment in cats
Authors: Robinson Alexandra R , Steagall Paulo V 
Published: October 2024

Objectives The aim of the study was to determine the effects of training on inter-rater reliability and agreement of Feline Grimace Scale (FGS) scoring by small animal practitioners. Methods Seven small animal veterinarians were asked to score a total of 50 images of cats in varying degrees of pain before and after training in FGS scoring. Participant scores were compared with those of an expert rater. Inter-rater reliability was analyzed using the intraclass correlation coefficient (ICC) before and after training (ICC <0.50 = poor reliability, 0.50–0.75 = moderate reliability, 0.76–0.90 = good reliability and >0.90 = excellent reliability). The Bland–Altman method was used to analyze the limits of agreement (LoAs) and bias between participants and the expert rater. Results After training, the ICC classification improved for each action unit (ear position, orbital tightening, muzzle tension, whiskers change and head position). The inter-rater reliability for the total FGS ratio scores before and after the FGS training session was moderate (ICC = 0.75; 95% confidence interval [CI] 0.66–0.83) and good (ICC = 0.80; 95% CI 0.73–0.87), respectively. Before training, LoAs were −0.277 to 0.310 with a bias of 0.016. After training, LoAs were −0.237 to 0.255 with a bias of 0.008. The bias was low (<0.1) both before and after training and LoAs did not span the FGS analgesic threshold (0.39). Conclusions and relevance Training in FGS scoring improved inter-rater reliability and agreement among seven small animal veterinarians and the veterinarians’ skills in pain assessment.
Microbial Contamination and Meat Handling Practices in Hawassa City Butcher Shops, Ethiopia
Authors: Kenaw Zebitu , Ejeso Amanuel , Deresse Dawit , Olkeba Beekam Kebede 
Published: October 2024

Background: Unsafe meat handling in butcher shops exacerbates microbial contamination, contributing to widespread food-related infections, particularly in developing countries like Ethiopia. In Ethiopia, microbial contamination in the meat supply chain is pervasive due to limited knowledge, inadequate hygiene practices, insufficient training, poor enforcement of food safety standards, and the absence of advanced diagnostic tools and regular microbial testing. This study aimed to assess the microbial load of meat, its contact surfaces, and meat handling practices of butcher shop workers in Hawassa city, Ethiopia. Methods: A cross-sectional study was conducted from March to April 2023 among butcher shop workers in Hawassa city, Ethiopia. One hundred forty-four (144) swab samples were collected, and the microbial load was evaluated by serial dilution method and counted using standard procedures. A total of 52 workers were interviewed to assess meat handling practices. Descriptive statistics were used to analyze survey and laboratory data. Results: The findings of this study revealed that the levels of Total Plate Count, Enterobacteriaceae, and staphylococci from meat samples collected from the butchers were 6.14, 5.58, and 5.23, respectively. The levels of Total Plate Count, Enterobacteriaceae, and staphylococci in the swab samples collected from knives, chopping boards, and weighing boards were 5.66, 5.27, and 5.28; 5.61, 5.33, and 5.03; and 5.29, 4.97, and 4.91, respectively. In the butcher shops, 83% of the meat was exposed to flies without protection, and 64% of meat handling equipment was not disinfected. Conclusions: The Total Plate Count, Enterobacteriaceae and staphylococci levels in meat samples and swab samples collected from knives, chopping boards, and weighing boards were above acceptable levels. These findings suggest the presence of potential pathogenic microorganisms, likely due to poor personal hygiene of the workers, inadequate cleaning and sterilization in the butcher shops, and cross-contamination from sources, including paper money handled, and skin contact.
Artificial intelligence-assisted focused cardiac ultrasound training: A survey among undergraduate medical students
Authors: Soliman-Aboumarie Hatem , Geers Jolien , Lowcock Dominic , Suji Trisha , Kok Kimberley , Cameli Matteo , Galiatsou Eftychia 
Published: October 2024

Objectives: Focused cardiac ultrasound (FoCUS) is increasingly applied in many specialities, and adequate education and training of physicians is therefore mandatory. This study aimed to assess the impact of artificial intelligence (AI)-assisted interactive focused cardiac ultrasound (FoCUS) teaching session on undergraduate medical students’ confidence level and knowledge in cardiac ultrasound. Methods: The AI-assisted interactive FoCUS teaching session was held during the 9th National Undergraduate Cardiovascular Conference in London in March 2023 and all undergraduate medical students were invited to attend, and 79 students enrolled and attended the training. Two workshops were conducted each over 3-hour period. Each workshop consisted of a theoretical lecture followed by a supervised hands-on session by experts, first workshop trained 39 students and the second workshop trained 40 students. The students’ pre- and post-session knowledge and confidence levels were assessed by Likert-type-scale questionnaires filled in by the students before and immediately after the workshop. Results: A total of 61 pre-session and 52 post-session questionnaires were completed. Confidence level in ultrasound skills increased significantly for all six domains after the workshop, with the greatest improvement seen in obtaining basic cardiac views (p < 0.001 for all six domains). Students strongly agreed about the effectiveness of the teaching session and supported the integration of ultrasound training into their medical curriculum. Conclusions: AI-assisted interactive FoCUS training can be an effective and powerful tool to increase ultrasound skills and confidence levels of undergraduate medical students. Integration of such ultrasound courses into the medical curriculum should therefore be considered.
Effectiveness comparison between ustekinumab and infliximab for Crohn’s disease complicated with intestinal stenosis: a multicenter real-world study
Authors: He Xidong , Wang Yufang , Sun Jingyao , Li Yueqin , Ruan Gechong , Li Yue , Zheng Weiyang , Zhang Xiaolan , Zhan Rongrong , Ding Xueli , Liu Ailing , Chen Yijia , Hu Yiqun , Yang Hong , Qian Jiaming 
Published: October 2024

Background: The efficacy of ustekinumab (UST) and infliximab (IFX) in Crohn’s disease (CD) patients with intestinal stenosis remains uncertain. Objective: This study aims to compare the efficacy of UST and IFX in the treatment of CD patients with intestinal stenosis. Design: This was a retrospective and multicenter cohort study. Methods: In this retrospective study, we included CD patients treated with IFX or UST at five centers. We assessed the clinical response rate at weeks 12 and 24, steroid-free clinical remission rate at weeks 24 and 52 for overall patients and those with stenosis, and objective examination (intestinal ultrasound and/or endoscopy) response rate at week 52 for stenosis patients. Results: A total of 211 CD patients (106 IFX and 105 UST) were included, with 119 (56 IFX and 63 UST) having intestinal stenosis. In the overall patient population, there were no significant differences in clinical response rate and steroid-free clinical remission rate at weeks 12, 24, and 52 between the IFX and UST groups. In patients with stenosis, the steroid-free clinical remission rate at week 52 was significantly lower in the IFX group compared to the UST group (51.79% IFX vs 69.84% UST, p = 0.044). The objective examination response rate did not significantly differ between the IFX and UST groups at week 52 (66.67% IFX vs 76.19% UST, p = 0.690). In the UST group, steroid-free clinical remission rate was higher in bio-naïve patients than bio-experienced patients at week 24 (75.00% bio-naïve vs 55.38% bio-experienced, p = 0.043). Conclusion: UST may be considered a more advantageous treatment option for those CD patients with intestinal stenosis, as it has better steroid-free clinical remission rates compared to IFX.
Pre-treatment pan-immune-inflammation value as a prognostic marker of pazopanib in soft tissue sarcoma
Authors: Wu Cheng-Han , Lai Cheng-Lun , Hsu Yong-Chen , Hsu Chiann-Yi , Wang Yu-Chao , Lin Hsin-Chen 
Published: October 2024

Background: Increasingly, more evidence has shown that inflammation stress and the tumor microenvironment pose a negative effect on targeted therapy. The neutrophil-to-lymphocyte ratio is considered to be a surrogate biomarker of inflammation and can predict pazopanib treatment effect in non-adipocytic soft-tissue sarcoma (STS). The role of the pan-immune-inflammation value (PIV) in STS is still yet to be determined. Objectives: We sought whether the pre-treatment PIV could be applied to predict the response of pazopanib in STS. Design: We conducted a retrospective analysis of 75 patients who had been treated with pazopanib for recurrent or metastatic non-adipocytic STS. Methods: Our cohort was stratified into either a pre-treatment high PIV group with PIV ⩾310 ( n = 45) or a low PIV group with PIV <310 ( n = 30). We compared their clinical features and outcomes. Cox regression analysis was employed to determine the risk factors of disease progression and mortality. Kaplan–Meier survival curves were utilized to assess both the progression-free survival (PFS) and overall survival (OS). Results: The results revealed that a pre-treatment high PIV (⩾310) is a risk factor for progression under pazopanib (hazard ratio: 1.91; 95% confidence interval: 1.08–3.36; p = 0.025). The median PFS and OS of the pre-treatment high PIV group were found to be significantly lower than the low PIV group (0.33 vs 0.75 years; p = 0.023, 0.46 vs 1.63 years; p = 0.025). Conclusion: High pre-treatment PIV in STS patients may indicate an elevated risk of disease progression and mortality. Pre-treatment PIV reflects inflammation stress and acts as a practical biomarker for STS patients treated with pazopanib.
Second-line treatment of PD-1 and CTLA-4 blockade combined with liposomal irinotecan plus leucovorin and fluorouracil for advanced cholangiocarcinoma: study protocol of a single-arm, prospective phase II trial
Authors: Yang Heqi , Li Linjuan , Li Xiaofen , Ma Yuhang , Yang Yu , Cao Dan 
Published: October 2024

Background: Cholangiocarcinoma is a kind of malignant tumor that originates in the epithelium of the biliary tract. Although there are several options for second-line treatment for patients without specific genetic mutations, the overall treatment efficacy is disappointing. Second-line treatment which is composed of liposomal irinotecan plus fluorouracil and leucovorin significantly improved the treatment efficacy for advanced biliary tract cancer and extended patient survival. This study aims to evaluate the efficacy and safety of the combination of cadonilimab with liposomal irinotecan plus fluorouracil and leucovorin for advanced biliary tract cancer. Objectives: The primary objective of this study is to determine the objective response rate. The second objectives of this study are overall survival, progression-free survival, disease control rate, and adverse event incidence rate. Design: The study is a single-arm, prospective phase II clinical trial. In all, 51 patients who are diagnosed with locally advanced or metastatic bile tract cancer will be enrolled. Methods and analysis: Eligible participants will receive cadonilimab at a dosage of 6 mg/kg on day 1 of each 21-day cycle combined with intravenous liposomal irinotecan at a dosage of 70 mg/m2 for 90 min on day 1 plus leucovorin at a dosage of 400 mg/m2 for 30 min on day 1 and fluorouracil at a dosage of 400 mg/m2 for 46 h every 2 weeks. Discussion: Previous studies have suggested that there is a synergistic effect between the two treatment modalities. However, the potential of cadonilimab in bile tract cancer has not been explored. Hence, this trial is the first to investigate its efficacy and toxicity. In addition, the trial is also willing to explore potential biomarkers in patients with locally advanced and metastatic bile tract cancer. Trial registration: This study was registered on ClinicalTrials.gov with NCT06438822. Ethics: This study protocol and amendments have been approved by the Ethics Committee of West China Hospital (2024(791)).