bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic impact of tumor deposits in colorectal cancer: More than just N1c
Authors: Bhutiani Neal , Peacock Oliver , Uppal Abhineet , Hu Chung‐Yuan , Bednarski Brian K. , Taggart Melissa W. , Dasari Arvind , Morris Van K. , Kaur Harmeet , Kopetz Scott , Holliday Emma B. , Das Prajnan , You Y. Nancy , Chang George J. 
Published: September 2024

ABSTRACTBackgroundThe identification of tumor deposits (TD) currently plays a limited role in staging for colorectal cancer (CRC) aside from N1c lymph node designation. The objective of this study was to determine the prognostic impact, beyond American Joint Committee on Cancer N1c designation, of TDs among patients with primary CRC.MethodsPatients who had resected stage I–III primary CRC diagnosed between 2010 and 2019 were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer‐specific survival (CSS) stratified by TD status and lymph node (N) status was calculated using the Kaplan–Meier method and multivariable Cox proportional hazards regression analyses.ResultsIn total, 147,783 patients with primary CRC were identified. TDs were present in 15,444 patients (10.5%). The presence of TDs was significantly associated with adverse tumor characteristics, including advanced pathologic stage, nodal status, and metastasis status. The presence of TDs was associated with worse CSS (hazard ratio [HR], 3.12; 95% confidence interval [CI], 3.02–3.22), as it was for each given N category (e.g., N2a and TD‐negative [HR, 2.50; 95% CI, 2.37–2.64] vs. N2a and TD‐positive [HR, 3.75; 95% CI, 3.49–4.03]). The presence of multiple TDs was also associated with decreased CSS for each given N category compared with a single TD (e.g. N2a with one TD [HR, 3.09; 95% CI, 2.65–3.61] vs. N2a with two or more TDs [HR, 4.32; 95% CI, 3.87–4.82]).ConclusionsTDs were identified as an independent predictor of a worse outcome in patients with CRC. The presence of TDs confers distinctly different CSS and provides important prognostic information among patients with CRC and warrants further investigation as a unique variable in future iterations of CRC staging.
Proximity to cancer rehabilitation and exercise oncology by geography, race, and socioeconomic status
Authors: Schmitz Kathryn H. , Demanelis Kathryn , Crisafio Mary E. , Kennedy Mary A. , Schwartz Anna L. , Campbell Anna , Gorzelitz Jessica , Wood Kelley C. , Wilson Christopher M. , Scalise Raymond L. , Vincent Alex 
Published: September 2024

AbstractBackgroundCancer rehabilitation and exercise oncology (CR/EO) have documented benefits for people living with and beyond cancer. The authors examined proximity to CR/EO programs across the United States with respect to population density, race and ethnicity, socioeconomic status, and cancer incidence and mortality rates.MethodsThis cross‐sectional study was conducted in 2022–2023. Online searches were initiated to identify CR/EO programs. Geocoding was used to obtain latitudinal and longitudinal geospatial coordinates. Demographic data were abstracted from the 2020 5‐year American Community Survey. Cancer incidence and mortality data were obtained from the Centers for Disease Control and Prevention. US 2013 Rural‐Urban Continuum Code (RUCC) classification was used to define counties as either urban (RUCC 1–3) or rural (RUCC 4–9). Multivariable logistic regression was used to evaluate the association between being far from a program and census‐tract level factors.ResultsIn total, 2133 CR/EO programs were identified nationwide. The distance from a program increased with decreasing population density: rural tracts were 17.68 ± 0.24 miles farther from a program compared with urban tracts (p < .001). Program proximity decreased as the neighborhood deprivation index increased (p < .001). Exercise oncology programs were less common than cancer rehabilitation programs in tracts with a larger proportion of minority residents (p < .001).ConclusionsPrior research has documented that underrepresented populations have worse cancer‐related symptoms and higher cancer mortality. Herein, the authors document their findings that these same populations are less likely to have proximity to CR/EO programs, which are associated with improved cancer‐related symptoms and cancer mortality outcomes. To realize the positive outcomes from CR/EO programming, efforts must focus on supporting expanded programming and sustainable payment for these services.
Using context‐specific evidence to inform resource‐stratified cancer guidelines: A call for a new approach
Authors: Buckle Geoffrey C. , DeBoer Rebecca , Xu Mary Jue , Mrema Alita , Rubagumya Fidel , Velloza Jennifer , Falade Ayo S. , Van Loon Katherine 
Published: September 2024

AbstractClinical practice guidelines are widely used in oncology to guide clinical decision making and inform health policy and planning. In recent years, the National Comprehensive Cancer Network and the American Society of Clinical Oncology, as well as other international groups, have developed resource‐stratified guidelines to guide clinicians and policymakers on cancer diagnosis and management in settings with various levels of resource constraints. Current methods for developing resource‐stratified guidelines rely heavily on supporting evidence originating from high‐income countries. In this commentary, the authors discuss limitations of the existing methods to develop resource‐stratified guidelines and offer perspective on ways to strengthen the guidelines and their evidence base. Pulling from conceptual frameworks in the health policy domain, the authors outline a more inclusive approach to evidence synthesis that seeks to integrate the growing volume of cancer research emerging from low‐ and middle‐income countries. The authors also introduce a revised evidence framework that provides transparency into the generalizability of evidence within the guidelines. These changes have the potential to enhance resource‐stratified guidelines and bring us one step closer to the goal of evidence‐based guidelines that are appropriate for diverse settings and unique patient populations across the world.
Influenza vaccine effectiveness in immunocompromised patients with cancer: A Danish nationwide register‐based cohort study
Authors: Amdisen Lau , Pedersen Lars , Abildgaard Niels , Benn Christine Stabell , Cronin‐Fenton Deirdre , Sørup Signe 
Published: September 2024

AbstractBackgroundInfluenza vaccination is free of charge for Danish citizens with acquired immunodeficiency but recommendations do not specifically target patients with cancer. This study investigated whether influenza vaccination reduces the main outcome of overall mortality and the secondary outcomes of influenza requiring treatment, pneumonia, myocardial infarction, stroke, heart failure, and venous thromboembolism in patients with cancer.MethodsThis was a register‐based nationwide cohort study. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) for overall mortality and secondary outcomes were estimated using Cox proportional hazards models. Analyses were conducted separately for four subgroups: patients aged <65 years with solid tumors, patients aged ≥65 years with solid tumors, patients aged <65 years with hematological cancer, and patients aged ≥65 years with hematological cancer.ResultsA total of 53,249 adult patients with solid tumors who received chemotherapy and 22,182 adult patients with hematological cancer were followed for up to five influenza seasons in the study period of 2007–2018. In the main analysis covering December–March, influenza vaccination was associated with reduced overall mortality in all four subgroups. The reduction was most pronounced in patients with hematological cancer aged <65 years (aHR, 0.66; 95% CI, 0.51–0.87) and smallest in patients with solid tumors aged <65 years (aHR, 0.91; 95% CI, 0.84–0.99). In sensitivity analyses covering January–March, the aHR was 0.87 (95% CI, 0.65–1.16) in patients with hematological cancer aged <65 years and 1.01 (95% CI, 0.92–1.10) in patients with solid tumors aged <65 years. Results for the secondary outcomes were inconclusive.ConclusionsThe results of this study cannot reject that influenza vaccination reduces overall mortality in immunocompromised patients with cancer. The results must be interpreted with caution because of potential unmeasured confounding, which can result in the overestimation of influenza vaccine effectiveness.
Effects of exercise therapy on chemotherapy delivery and response in primary breast cancer: A secondary analysis of a randomized trial
Authors: Iyengar Neil M. , Scott Jessica M. , Lee Jasme , Lavery Jessica A. , Foug Katherine L. , Lee Catherine P. , Michalski Meghan G. , Chun Su S. , Harrison Jenna , Moskowitz Chaya S. , Jones Lee W. 
Published: September 2024

AbstractBackgroundWhether structured exercise therapy improves chemotherapy delivery, tolerability, and tumor response is unclear.MethodsThis was a secondary analysis of a phase 2 trial investigating exercise therapy (n = 72) versus usual care (n = 72) in patients with primary breast cancer. Exercise therapy comprised individualized treadmill walking three times weekly for 20–50 minutes per session at 55%–100% of pretreatment exercise capacity. Chemotherapy delivery was assessed according to the relative dose intensity (RDI), tolerability was assessed according to patient‐reported outcomes and blood laboratory values, and response was assessed based on the pathologic complete response rate in patients who received neoadjuvant chemotherapy.ResultsIn the exercise therapy group, 51 patients (71%) reached 100% RDI (median, 100%; interquartile range, 100%–100%) compared with 41 patients (57%) in the usual care group (median, 100%; interquartile range, 95%–100%; p = .08). Tolerability was similar in both groups; the rates of grade 3 or higher neutropenia and anemia were 22% versus 39% and 7% versus 10% in the exercise and usual care groups, respectively. In patients who received anthracyclines (n = 104), 41 (77%) had 100% chemotherapy RDI in the exercise therapy group versus 29 (57%) in the usual care group (p = .026). In the neoadjuvant chemotherapy subgroup (n = 51 tumors), the postneoadjuvant therapy (yp) pathologic complete response (ypT0ypN0) rate was 27% (95% confidence interval, 12%–50%) in the exercise therapy group compared with 28% (95% confidence interval, 13%–47%) in the usual care group (p > .9).ConclusionsIn patients with primary breast cancer, exercise therapy was associated with improved delivery of anthracycline‐based chemotherapy. Although exercise therapy was not significantly associated with tumor response, effects varied by tumor subtype (trial registration: Clinicaltrials.gov identifier NCT01943695).
Survival outcomes of neoadjuvant versus adjuvant therapy in patients with T1c, node‐negative, human epidermal growth factor receptor 2–positive breast cancer: A Surveillance, Epidemiology, and End Results population‐based study
Authors: Wang Xuelian , Shang Yuhang , Zhang Jiayang , Liu Jiangwei , Fang Zhengbo , Liu Yansong , Cheng Weilun , Duan Yunqiang , Hu Anbang , Zhang Jiarui , Li Mingcui , Li Yanling , Zhang Hanyu , Rong Zhiyuan , S. Shakila Suborna , Kong Fanjing , Guo Baoliang 
Published: September 2024

AbstractBackgroundPersistent debates exist regarding the superiority of neoadjuvant therapy (NAT) over adjuvant therapy (AT) for patients with T1c, node‐negative, human epidermal growth factor receptor 2–positive (HER2+) breast cancer, and relevant guidelines for these patients are lacking.MethodsData on patients with T1cN0M0‐stage HER2+ breast cancer who received chemotherapy and surgery were extracted from 2010 to 2020 from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was used to create well‐balanced cohorts for the NAT and AT groups. Kaplan–Meier (KM) analysis and Cox proportional hazards models were used to assess the differences between NAT and AT in terms of overall survival (OS) and breast cancer–specific survival (BCSS). Additionally, logistic regression models were used to explore factors associated with response to NAT.ResultsAfter PSM, 2140 patient pairs were successfully matched, which achieved a balanced distribution between the NAT and AT groups. KM curves revealed similar OS and BCSS between patients receiving NAT and those undergoing AT. A multivariate Cox model identified achieving pathological complete response (pCR) after NAT, compared with AT, as a protective prognostic factor for OS (hazard ratio, 0.52; 95% CI, 0.35–0.77; p < .001) and BCSS (hazard ratio, 0.60; 95% CI, 0.37–0.98; p = .041). A logistic regression model revealed that White race and hormone receptor–negative status independently predicted pCR.ConclusionsFor patients with T1cN0M0‐stage HER2+ breast cancer, NAT demonstrated comparable OS and BCSS to AT. Patients who achieved pCR after NAT exhibited significantly better survival outcomes compared with those who received AT.
Pharmacokinetics of Two Formulations of Altrenogest Administered to Mares
Authors: Loy Jaymie , Cawley Adam , Sornalingam Kireesan , Scrivener Colin J. , Keledjian John , Noble Glenys K. 
Published: September 2024

ABSTRACTAltrenogest is a synthetic progestin that suppresses reproductive behaviours and assists pregnancy maintenance in female horses. Two formulations are available, a 'weekly' intramuscular injection and a daily oral formulation. Altrenogest administration has returned positive swabs for steroids; consequently, using injectable altrenogest in racing mares is prohibited. Oral administration may be permitted in race mares if there is one clear day between dosing and racing. The only pharmacokinetic data available were generated from geldings. Therefore, to assist veterinarians and analysts in determining accurate dosing and detection intervals, pharmacokinetic analysis using mares is required. Blood samples were taken from 10 mares pretreatment to obtain baseline concentrations. Mares were administered altrenogest, either oral (PO; 0.044 mg/kg; daily for 15 days) or intramuscular (IM; 0.3 mg/kg; twice; Days 0 and 7). On the first and last treatment day, blood samples were taken at designated times post dosing. After a 3‐week washout, mares received the alternative treatment with sampling repeated. At the initial dose, for IM administration mean (± SD) plasma altrenogest Cmax was 18.0 ± 6.6 ng/mL at 7.9 ± 3.9 h compared with PO dosing 13.2 ± 5.8 ng/mL at 0.8 ± 0.8 h. Plasma Cmax on the final day was significantly higher (p = 0.002 [IM]; p = 0.006 [PO]). At 24 h post final oral treatment, mean (± SD) plasma altrenogest was 1.0 ± 0.8 ng/mL and at 48 h were 0.65 ± 0.5 ng/mL. Plasma concentrations well exceeding this may indicate that the one clear day rule or dosage recommendations have not been adhered to.
High‐Throughput Equine Doping Controls on a Trapped Ion Mobility Quadrupole‐Time‐of‐Flight Mass Spectrometer: Technical Considerations of dia/slice/prmPASEF Applied to the Long‐Term Detection of Monoclonal Antibodies
Authors: Delcourt Vivian , Pinetre Justine , Chabot Benjamin , Barnabé Agnès , Cacault Marie , Loup Benoit , Becher François , Fenaille François , Popot Marie‐Agnès , Garcia Patrice , Bailly‐Chouriberry Ludovic 
Published: September 2024

ABSTRACTData‐independent acquisition (DIA) methods employing a scanning quadrupole were recently described across multiple platforms. These strategies display remarkable performances in untargeted proteomics studies thanks to rapid duty cycles, leading to ultrashort liquid chromatography gradients while maintaining enough data points per peaks when coupled to fast‐scanning mass analyzer. In this article, we perform the evaluation of three data acquisition strategies named diaPASEF,slicePASEF, and prmPASEF on a trapped ion mobility spectrometry quadrupole‐time‐of‐flight (TIMS‐Q‐TOF) mass spectrometer for high‐throughput doping control screening analyses. We report that slicePASEF outperforms diaPASEF and is almost as sensitive as prmPASEF in detecting humanized monoclonal antibodies for several weeks in equine plasma after administration. We observed that diaPASEF is still providing the best performances in untargeted proteomics studies employing high amounts of input materials, which is linked with the high complexity of slicePASEF data and current processing algorithms.
Suitability of Hair Testing in Medical Dispensing Errors: A Fatal Case of Gliclazide Poisoning
Authors: Riess S. , Klinger N. , Roussel O. , Cheze M. , Gonçalves R. , Cirimele V. 
Published: September 2024

ABSTRACTA patient was prescribed a new treatment, 40 mg furosemide. Her pharmacist mistakenly dispensed 40 mg gliclazide instead. After 3 weeks of treatment, the patient was found in a coma, was hospitalised and died after a week. Hair sample was collected during post‐mortem examination and tested for gliclazide on three 2 cm sections, starting at the root end. Hair strands were decontaminated, segmented and incubated in the presence of diazepam‐d5, and a solid–liquid extraction has been performed. Finally, toxicological analyses were performed by UFLC Shimadzu Prominence ‐ MS/MS Sciex 6500 QTRAP. Gliclazide was found on the proximal (238 pg/mg), median (77 pg/mg) and distal (69 pg/mg) segments. The concentration in the proximal segment was largely higher than in the other two, which demonstrates repeated intake of gliclazide by the patient during at least the last 2 months before death. The lower concentrations in the medial and distal segments, as well as a part of the concentration in the proximal segment, may be linked to external hair contamination. These could be due to either radial sweat diffusion, possibly occurring in the last week hospitalisation of the patient, or to biological fluids contamination during post‐mortem examination. This case illustrates the opportunity to confirm slow and fatal chronic poisoning by gliclazide using hair analysis and shows the benefit of hair testing for the investigation of medical or dispensing errors.
La(OTf)3‐Mediated [3+3]‐Annulation of Benzoxepines and Aminocrotonates: Easy Access to Bridged Bicyclic Benzoxepine Heterocycles†
Authors: Teja Kolla Sai , Hariprasad Kurma Siva , Balasubramanian Sridhar , Raju Bhimapaka China 
Published: September 2024

AbstractA new and effective method for making bridged bicyclic benzoxepine derivatives were devised through the intermolecular [3+3]‐annulation of benzoxepine‐3‐carboxylates with aminocrotonates in the presence of La(OTf)3. The compounds were formed through reactions involving the benzoxepine moiety's C‐3 and C‐5 carbons to produce C−C and C−N bonds. One of the compound structure (±) 12‐ethyl‐6‐methyl‐3‐hydroxy‐5‐methyl‐2,3,4,7‐tetrahydro‐3,7‐methano benzo[h][1,4]‐oxazonine‐6,12‐dicarboxylate was confirmed by single crystal X‐ray analysis.
Matcha and exercise synergy: Elucidating mechanisms and central signaling pathways modulating glycolipid metabolism in high‐fat diet‐induced obese mice
Authors: Zhou Jihong , Ding Lejia , Chen Wei , Tan Yanliang , Xie Dengchao , Wang Yuefei 
Published: September 2024

AbstractMatcha green tea, renowned for its rich composition of catechin, theanine, caffeine, and fiber‐bound polyphenols, distinguishes itself with heightened bioavailability and promising potential in addressing obesity and metabolic disorders. Our comprehensive analysis delved into matcha's components and antioxidant activity. Employing a multi‐omics approach, we explored the synergistic effects of matcha combined with voluntary exercise, focusing on anti‐obesity outcomes in high‐fat diet mice. Our findings revealed that matcha co‐exercise significantly mitigates glycolipid metabolism abnormalities, increasing serum antioxidant enzymes. This combination notably influences peripheral metabolism, especially amino acids and their metabolisms. Moreover, the observed activation of the BMP‐SMAD signaling in the hypothalamus implies a central regulatory role mediating matcha co‐exercise effects. Collectively, these findings underscore matcha's potential as a robust adjunct in mitigating obesity through antioxidant and metabolic regulation, supporting its use as a promising supplement to enhance exercise benefits in combating obesity.
Global, regional, and national burdens of Alzheimer's disease and other forms of dementia in the elderly population from 1999 to 2019: A trend analysis based on the Global Burden of Disease Study 2019
Authors: Su Mengdan , Wang Tianhong , Zou Congcong , Cao Keyu , Liu Fei 
Published: September 2024

AbstractDementia represents a significant health issue, afflicting both patients and their families. To assess the global trends in the incidence, prevalence, mortality, and disability‐adjusted life years (DALYs) of Alzheimer's disease (AD) and other dementias in the elderly population, the Global Burden of Disease Study (1999−2019) was used. The average annual percentage change (AAPC) was estimated using linear regression. Stratified analysis of the global trends by age, sex, region, national level, and social development index (SDI) were also performed. The global incidence of AD and other dementias increased from 507.96 per 100,000 in 1990 to 569.39 per 100,000 in 2019, showing a significant increase in this period. In males, the incidence increased from 387.56 per 100,000 population in 1990 to 462.40 per 100,000 in 2019 (AAPC = 0.61), whereas females experienced a slower rise (AAPC = 0.31) and had a higher incidence in 2019 (662.93 per 100,000 population). The most significant increase was observed in individuals aged 60−64 and those in the middle‐SDI quintile. Regionally, the high‐income Asia Pacific had the highest incidence (890.01 per 100,000 population) and DALYs (3043.86 per 100,000) in AD and other dementias in 2019. As for national trends, Japan had the most pronounced increase in the incidence and DALYs of AD and other dementias during the 1990−2019 period. These findings highlight the growing burden of dementias on life expectancy at a population level, which is significant for healthcare professionals and decision‐makers to conduct the ongoing debate on the policy of AD and other dementias.
New players in the landscape of renal cell carcinoma bone metastasis and therapeutic opportunities
Authors: Cesana Beatrice , Cochet Claude , Filhol Odile 
Published: September 2024

AbstractApproximately one‐third of advanced renal cell carcinoma (RCC) patients develop osteolytic bone metastases, leading to skeletal complications. In this review, we first provide a comprehensive perspective of seminal studies on bone metastasis of RCC describing the main molecular modulators and growth factor signaling pathways most important for the RCC‐stimulated osteoclast‐mediated bone destruction. We next focus on newer developments revealing with in‐depth details, the bidirectional interplay between renal cancer cells and the immune and stromal microenvironment that can through epigenetic reprogramming, profoundly affect the behaviors of transformed cells. Understanding their mechanistic interactions is of paramount importance for advancing both fundamental and translational research. These new investigations into the landscape of RCC‐bone metastasis offer novel insights and identify potential avenues for future therapeutic interventions.