bluuebunny/crossref_metadata_2025 huggingface dataset:
Redistribution of soil water by mature trees towards dry surface soils and uptake by seedlings in a temperate forest
Authors: Hafner B. D. , Hesse B. D. , Grams T. E. E.
Published: January 2025

Hydraulic redistribution is considered a crucial dryland mechanism that may be important in temperate environments facing increased soil drying–wetting cycles. We investigated redistribution of soil water from deeper, moist to surface, dry soils in a mature mixed European beech forest and whether redistributed water was used by neighbouring native seedlings.

In two experiments, we tracked hydraulic redistribution via (1) 2H labeling and (2) 18O natural abundance. In a throughfall exclusion experiment, 2H water was applied to 30–50 cm soil depth around mature beech trees and traced in soils, in coarse and fine roots, and in the rhizosphere. On five additional natural plots, the 18O signal was measured in seedlings of European beech, Douglas fir, silver fir, sycamore maple, and Norway spruce at dawn and noon after a rain‐free period.

We found a significant enrichment in 2H in surface soil fine roots of mature beech, and an indication for transfer of this water into their rhizosphere, suggesting hydraulic redistribution from deeper, moist to drier surface soils. On four of the five additional plots, δ18O of seedlings' root water was lower at dawn than at noon. This indicated that dawn root water originated from soil layers deeper than the seedlings' rooting depth, suggesting hydraulic redistribution by neighbouring mature trees.

Hydraulic redistribution equated to about 10% of daily transpiration in mature beech trees, and contributed to root water in understory seedlings, emphasizing hydraulic redistribution as a notable mechanism in temperate forests. Transport mechanisms and potential of different tree species to redistribute water should be further addressed.
A Special Insight on the Causal Agents and Mode of Occurrence of Japanese Encephalitis (JE) Infections in Rural Regions of Assam, India
Authors: Talukdar Oli , Bhattacharya Satya Sundar , Gogoi Nayanmoni
Published: January 2025

Introduction

Japanese Encephalitis (JE) is a life‐threatening disease, especially in the Indian subcontinent. Knowledge about the nature and ecology of the dispersal of JE virus (JEV) vectors needs to be increased. This study mechanistically explores the ecology of JEV vectors and the mode and frequency of occurrence of Acute Encephalitis Syndrome (AES) and JEV infections.

Methods

We established a linear relationship between environmental variables and JEV infection by JEV vectors (mosquitoes)—Culex tritaeniorhynchus, Culex vishnui, and Culex pseudovishnui. The relative abundance of three mosquito species was evaluated, and the JE Sample Positivity Rate (SPR) and JE Case Fatality Rate (CFR) were computed.

Results

Culex vishnui had a high abundance in residential areas during the transition from hot‐dry (77.34%) to hot‐wet period (78.66%) at temperatures between 31°C and 34°C and relative humidity of 80%–85.3%; this period also coincided with occurrence of AES (39 cases in hot‐dry and 88 cases in hot‐wet period) and JE (8 instances in hot‐dry and 31 cases in hot‐wet period). JE infection dominated near rainfed rice fields (rainfall: R = 0.67 at p < 0.05; rainy days: R = 0.74, p < 0.01). SPR was up to 32.28%, and CFR was as high as 42.86%; JEV infection was concentrated in adult male humans near rice fields (15.66%).

Conclusions

Climate modulation over the years can influence the distribution of Culex vishnui and, hence, AES and JE cases. JEV infections tend to rise in JE hotspot regions, especially near rice fields. Thus, comprehensive epidemiological investigations will help prevent a silent outbreak of JE.
Sociodemographic Determinants of Expenditure on Soft Drinks among Households in Malaysia
Authors: Sa'adun Siti Hawa , Cheah Yong Kang , Md Salleh Mohd Faisol
Published: January 2025

High consumption of soft drinks can lead to various chronic diseases, most notably, diabetes and heart disease. The objective of the present study is to examine sociodemographic factors associated with consumption expenditure on soft drinks among households in Malaysia. Data from the Malaysia Household Expenditure Survey (n = 52,671) were used for secondary analysis. The dependent variable was monthly household expenditure on soft drinks. The independent variables were age, gender, education, marital status, region, income and ethnicity. The present study used a two-part model to estimate factors affecting consumption and amount decisions of soft drinks. Results showed that age, gender, education, marital status, region, income and ethnicity were associated with consumption of soft drinks. Having household heads aged more than 30 years decreased the likelihood of consuming soft drinks. Soft drinks expenditure was positively associated with being married, the middle-income group, Chinese ethnicity and low-education levels. In conclusion, household expenditure on soft drinks is closely correlated with a wide range of sociodemographic factors. Findings from the present study can assist policymakers in developing a more effective approach that focuses on decreasing household consumption of soft drinks.
Fractal Analysis of Vibration Signals for Assessing Mechanical Material Properties Under Different Impact Forces
Authors: Ahmad Zakri Ahmad Zaim , Ahmat Zainuri Nuryazmin , Nuawi Mohd Zaki , Razali Noorhelyna
Published: January 2025

Understanding the mechanical properties of materials is essential in science and engineering to enhance product durability, safety, and performance, and to prevent structural failures. This study applies fractal analysis to investigate vibration signals  recorded by piezo film sensors during impact testing on four square-shaped materials: brass, copper, mild steel, and stainless steel. Using an impact hammer, each material was subjected to impact forces ranging from 300N to 800N. Vibration data was captured and analyzed in MATLAB using a box-counting algorithm to calculate fractal dimensions. The findings revealed a notable correlation between the calculated fractal dimensions and two critical mechanical properties, Poisson’s ratio and Young’s modulus. The fractal dimension is inversely ordered relative to the Poisson’s ratio values of the materials, while the order of the fractal dimension aligns with the order of Young’s modulus values. This suggests that materials with higher Young’s modulus values also display higher fractal dimensions, whereas materials with higher Poissons ratios exhibit lower fractal dimensions. These insights indicate that fractal analysis of vibration signals provides a reliable,efficient, and cost-effective alternative to conventional methods for evaluating material properties. This approach holds significant potential for non-destructive testing applications, especially in fields requiring rapid and economical material assessments, such as aerospace, automotive, and construction.
Is exposure to a climate-related disaster associated with recent experiences of intimate partner violence among women? A post hoc analysis of survey data from rural Samoa
Authors: Mannell Jenevieve , Tevaga Pepe , Isaako Papali’i Ene , Alisi-Fesili Fa’afetai , Apelu Louisa , Moananu Kaisarina , Faumuina Taiaopo , Sinclair Lewis , Tanielu Helen , Lowe Hattie , Brown Laura J , Copas Andrew
Published: January 2025

Background

There is growing evidence that climate-related disasters increase rates of intimate partner violence (IPV) against women. However, there are only limited understandings of the size and nature of such associations needed to inform appropriate programming. Gaps in evidence are particularly pronounced in the Pacific—one of the regions most at risk of increased disasters from climate change.

Methods

We analysed data from 450 men and 707 women collected as part of cross-sectional study of IPV experience, risk and protective factors in rural Samoan villages. Data were analysed using multivariable logistic regression models to assess associations between (1) men’s and women’s exposure to climate-related disasters and their mental health and (2) women’s exposure to climate-related disasters and their risk of IPV in the previous 12 months.

Findings

Reported symptoms of depression and anxiety were associated with having experienced a disaster. Those who reported experiencing a disaster 2–3 times had 61% greater odds of reporting depression (OR 1.61; 95% CI 1.00 to 2.58) and 88% greater odds of reporting anxiety (OR 1.88; 95% CI 1.01 to 3.49), in comparison to those who reported never experiencing a disaster. Women who reported experiencing 2–3 disasters had more than twice the odds of experiencing recent IPV (adjusted OR, aOR 2.37, 95% CI 1.77 to 3.19), while those who reported experiencing 4+ disasters had over 8 times the odds (aOR 8.12; 95% CI 2.02 to 32.61).

Interpretation

This is one of the first studies in the Pacific region to provide quantitative evidence of associations between exposure to climate-related events and women’s experiences of IPV. We identify a clear dose–response relationship between higher exposure to climate-related events and an increased risk of IPV for women. This points to the role of cumulative stress from experiencing repeat disasters in driving higher rates of IPV in climate-affected regions.
Narrative review of comprehensive management strategies for diabetic retinopathy: interdisciplinary approaches and future perspectives
Authors: Pei Xiaoting , Li Zhijie
Published: January 2025

This review examines the epidemiological trends, pathophysiologic mechanisms, and current and future therapeutic strategies for diabetic retinopathy (DR), focusing on innovative management countermeasures in the face of this global public health challenge. As the number of patients with diabetes continues to increase, DR, as one of its major complications, poses a significant threat to global visual health. This review not only summarises the latest advances in personalised treatment and emerging therapeutic modalities (such as anti-vascular endothelial growth factor therapy, laser treatment, surgical procedures and cutting-edge gene and stem cell therapies) but also emphasises the revolutionary potential of telemedicine technologies and digital health platforms to improve DR screening and adherence among people with diabetes. We show how these technological innovations, especially in resource-limited settings, can achieve early diagnosis and effective treatment, thereby significantly reducing the public health burden of DR. In addition, this article highlights the critical role of interdisciplinary teamwork in optimising the comprehensive management of DR, involving close collaboration among physicians, researchers, patient education specialists and policy-makers, as well as the importance of implementing these innovative solutions through societal engagement and policy support. By highlighting these innovative strategies and their specific impact on improving public health practices, this review offers new perspectives and strategies for the future management of DR, with the goal of promoting the prevention, diagnosis and treatment of DR worldwide, improving patient prognosis and enhancing quality of life.
Sickness absence trajectories among young employees in their first full-time employment and subsequent long-term sickness absence: a Danish register-based cohort study
Authors: Sørensen Jeppe Karl , Mathisen Jimmi , Bültmann Ute , Lallukka Tea , Melchior Maria , Rod Naja Hulvej , Pedersen Jacob , Stansfeld Stephen , Rugulies Reiner , Christensen Karl Bang , Madsen Ida
Published: January 2025

Background

Sickness absence (SA) poses an important and costly societal and public health challenge. However, no previous studies have investigated SA trajectories among individuals in their first full-time employment, delving into the contribution of early SA to future long-term absence among young employees. We aimed to identify SA trajectories in young full-time employees and explore them as risk markers for subsequent long-term SA (LTSA).

Method

In a nationwide register-based cohort of 91 633 young employees (aged 15–30) entering the Danish labour market between 2010 and 2018, we applied group-based multi-trajectory modelling to identify SA trajectories based on daily information on SA during the first year of full-time employment. Proportional hazard models were used to examine associations between trajectory groups and subsequent 2-year risk of LTSA after the first year (>30 days).

Results

A model with three distinct SA trajectory groups was selected: (1) no or few shorter SA spells (59% for women, 62% for men), (2) frequent shorter spells (36% for women, 34% for men) and (3) frequent longer spells (6% for women, 4% for men). A clear social and health gradient in SA trajectories was identified with individuals with frequent shorter or frequent longer SA spells having lower education and a history of mental health problems. Compared to having no or few shorter spells, belonging to trajectories with frequent shorter or longer spells was associated with higher risk of subsequent LTSA (fully adjusted HRs ranging from 1.82 to 2.21).

Conclusion

Around 40% of young employees’ SA was characterised by frequent shorter or longer spells during the first year of full-time employment, constituting an early risk marker for future LTSA. More attention should be paid to young individuals who, at the beginning of their work life, show increased SA patterns.
Burden of disease attributable to high body mass index in Belgium: a comparative risk assessment analysis
Authors: Gorasso Vanessa , Vandevijvere Stefanie , Nusselder Wilma Johanna , De Pauw Robby , Hilderink Henk , Nayani Sarah , Van der Heyden Johan , De Smedt Delphine , Devleesschauwer Brecht
Published: January 2025

Background and methods

High body mass index (BMI) is a major risk factor for several non-communicable diseases. The increasing concern about the health and economic burden of BMI makes it essential for countries to track their progress on major modifiable risk exposures. The aim of the study is to estimate the burden attributable to high BMI in Belgium, in terms of years of life lost due to disability (YLD), years of life lost due to premature mortality (YLL) and disease costs, using comparative risk assessment. We followed the general framework established in the Global Burden of Diseases, Injuries and Risk Factors study. Population attributable fractions were calculated for the year 2018 for selected health outcomes using local estimates of BMI and burden of disease estimates from the Belgian Burden of Disease study.

Results

According to our figures, around 37 800 YLD, 56 000 YLL and €1.85 billion in healthcare costs can be attributed to a high BMI. Diabetes had the highest number of YLD attributable to high BMI followed by musculoskeletal disorders. Cardiovascular diseases accounted for the highest burden in terms of YLL attributable to high BMI, followed by diabetes and different forms of cancers (i.e., breast, colon and rectum and oesophageal cancer).

Conclusion

A substantial proportion of the burden of disease could be prevented when reducing BMI in Belgium. This evidence on the impact of risk factors is important for monitoring disease burdens and setting priorities for health prevention policies.
Acceptability of digital health intervention during pregnancy to inform women about postpartum contraception (DIGICAP): a pilot randomised controlled study
Authors: Cooper Michelle , Free Caroline J , Kuan Kevin Ka-Wing , McCabe Karen , Osei-Asemani Emmanuela , Opondo Charles , Cameron Sharon
Published: January 2025

Background

Pregnancy within a year of childbirth has negative impacts on women and their children’s health. We developed a digital health intervention (DHI) to empower women in contraceptive choices postpartum. Our pilot randomised controlled trial (RCT) aimed to establish the feasibility of a main RCT of the effects of the DHI compared with standard care on long-acting contraception use.

Methods

Our pilot RCT recruited 52, 20–24 weeks pregnant women in NHS Lothian, UK between October 2022 and April 2023. Participants were randomised 7:3 to receive either the DHI (n=37) in addition to standard care, or standard care alone (n=15). Telephone survey follow-up was at 24 weeks’ gestation and 6 weeks postpartum. Semi-structured qualitative interviews (n=10) were conducted with participants receiving the DHI.

Results

All eligible women joined the study and completed follow-up. All intervention participants found the animation highly acceptable; one participant requested text message discontinuation. We completed followed up on 37/37 (100%) of participants. DHI participants reported they valued access to credible contraceptive information that supported decision making in a non-pressurised way.

Conclusions

Our DHI is highly acceptable and a trial is feasible. A larger trial is needed to establish if the DHI increases uptake of long-acting reversible contraception postpartum and reduces unintended pregnancies within 12 months of childbirth.

Trial registration number

(Trial registrationISRCTN48521918).
SARS-CoV-2 seropositivity amongst healthcare workers in South Africa during the Omicron wave: natural infection versus vaccination
Authors: Hoffmann Daniel J , Meyer Pieter W A , Worsley Catherine M , van der Mescht Mieke A , Visser A , Pillay Tahir S
Published: January 2025

Aims

Concerns over population-level immunity have been heightened with each successive wave of COVID-19, prompting questions about whether it is primarily derived from vaccination efforts or from previous natural infections with the virus. We wished to determine the seroprevalence of SARS-CoV-2 antibodies among healthcare workers (HCWs) in Pretoria (Tshwane), South Africa, and to establish whether they were derived from vaccination or natural infection.

Methods

Serum samples were collected from HCWs during the fourth wave of COVID-19 between 1 December 2021 and 13 March 2022. The samples were tested using the Abbott SARS-CoV-2 Spike IgG (S-IgG), IgM (S-IgM) and the SARS-CoV-2 Nucleocapsid IgG (NC-IgG) kits.

Results

Of the 221 participants, 76% (n=168) were women and 24% (n=53) were men. A total of 96.4% (n=213) of the participants were vaccinated. Natural infection-derived antibodies were detected in 23% (n=51) of participants, and vaccine-derived antibodies in 74% (n=164) of the HCWs.

Conclusions

Even after three waves of COVID-19, HCWs derived most of their detectable antibodies from vaccination. Vaccination remains an essential tool to protect HCWs and patients from SARS-CoV-2 infection.
Low-positive controls for monitoring progesterone receptor immunohistochemical staining
Authors: Lin Yu-Hsun , Hang Jen-Fan , Yang Ching-Fen , Hsu Chih-Yi
Published: January 2025

Aims

Progesterone receptor (PR) is a crucial prognostic marker in breast cancer. However, achieving consistent results in PR immunohistochemistry (IHC) remains challenging due to the lack of well-defined low-positive controls. This study aimed to identify benign tissues with consistent low-level PR expression to serve as ideal controls for IHC.

Methods

We evaluated PR expression in the squamous epithelium of the uterine cervix, nipple smooth muscle and pancreatic islets. QuPath digital image analysis was employed to compare the intensity and quantity of PR staining in target cells within a 2×2 mm area.

Results

The squamous epithelium of the secretory phase cervix, nipple smooth muscle and pancreatic islets displayed appreciable weak PR expression, with mean values of 73, 55 and 60 cells, respectively. Notably, 62% (8/13) of the 2×2 mm areas in the atrophic cervix were completely negative for PR expression. The coefficients of variation for weak PR-expressing cells in pancreatic islets (57.4%) and nipple smooth muscle (65.0%) were lower than those observed in the cervix (96.2%–222.0%). The squamous epithelium of the cervix, especially during the secretory phase, exhibited weak positivity confined to the basal layers, providing another viable control option. However, variations in PR expression may be influenced by physiological factors, such as hormonal fluctuations.

Conclusions

Pancreatic islets and nipple smooth muscle, with their consistent low-level PR expression, offer a promising solution to the challenges associated with PR IHC. This approach may help minimise variations resulting from differing staining methods across laboratories.
Association of thrombus enhancement with mortality following endovascular therapy in patients with acute anterior circulation stroke
Authors: Lin Kunxin , Guo Zhangbao , Guo Wenliang , Yue Chengsong , Li Jia , Lei Baoming , Liu Haifeng , Yang Yi , Tang Kun , Liu Wenhua , Wang Ning , Chen Wanjin , Zhao Wenlong
Published: January 2025

Background

Thrombus enhancement sign (TES) has emerged as a potential imaging biomarker in patients with acute ischemic stroke (AIS) undergoing endovascular thrombectomy (EVT).

Objective

To evaluate the prognostic value of TES on 90-day mortality and functional outcomes.

Methods

We conducted a prospective, two-center study involving 323 patients with AIS treated with EVT. TES was assessed by CT angiography (CTA) using thin-slab maximum intensity projection. The primary outcome was 90-day mortality; secondary outcomes included functional outcomes measured by the modified Rankin Scale (mRS). Subgroup, mediation, and sensitivity analyses were conducted to assess the predictive value of TES across different clinical factors.

Results

TES positivity was identified in 228 (70.6%) patients. TES-positive patients had a 90-day mortality rate of 25.0%, compared with 9.5% in TES-negative patients. TES was significantly associated with 90-day mortality in both univariate analysis (OR=4.275, 95% CI 1.765 to 10.350, P=0.001) and multivariate model 3 (adjusted OR=3.821, 95% CI 1.449 to 10.075, P=0.007). TES was also associated with 90-day mRS score 0–2 (OR=0.500, 95% CI 0.305 to 0.819, P=0.006) in univariate analysis.

Conclusion

TES is an independent predictor of 90-day mortality and poor functional outcomes in patients with AIS treated with EVT. TES can potentially serve as a valuable imaging biomarker for identifying high-risk patients.
MVST: A Multi-View Spatial-Temporal Model for Fine-Grained Crime Prediction
Authors: Wei Chang , Li Wengen , Zhang Yichao , Guan Jihong , Zhou Shuigeng
Published: January 2025

Given a specific region, crime prediction aims to predict the occurrence of various crime events within a certain period of time in future, which is of high significance for guaranteeing urban safety. In practice, crime events are usually affected by a variety of factors from different views, e.g., the attributes of the region, the correlations between different regions, and the correlations between different categories of crime events. Moreover, these correlations are dynamically changing over time, which makes it difficult to learn the regularity and patterns in crime data for achieving accurate prediction. To address this issue, we proposed a new
M
ulti-
V
iew
S
patial-
T
emporal (MVST) model for fine-grained crime prediction. MVST model first builds a static region graph to capture the similarity between regions in terms of region attributes such as census records and economy statistics, and creates a time-dependent graph to capture the dynamic correlations between regions based on human mobility data. Meanwhile, both static and dynamic graphs are created to capture the correlations between different categories of crime events. After that, those graphs created from different views are fused together with a multi-view graph fusion module to achieve crime prediction with fine-grained time granularities, e.g., 4 hours and 12 hours. According to the experiments on two real crime datasets, our MVST model obviously outperforms existing crime prediction methods. The code of MVST model is available at 
https://github.com/weichang811/MVST
.
Supplementary Tables 1 from Hormone Receptor–Positive HER2-Negative/MammaPrint High-2 Breast Cancers Closely Resemble Triple-Negative Breast Cancers
Authors: Rios-Hoyo Alejandro , Xiong Kaitlyn , Dai Jiawei , Yau Christina , Marczyk Michal , Garcia-Milian Rolando , Wolf Denise M. , Huppert Laura A. , Nanda Rita , Hirst Gillian L. , Cobain Erin F. , van ’t Veer Laura J. , Esserman Laura J. , Pusztai Lajos
Published: January 2025

Supplementary Tables
Supplementary Table S2 from A Phase III Randomized Trial of Integrated Genomics and Avatar Models for Personalized Treatment of Pancreatic Cancer: The AVATAR Trial
Authors: Sarno Francesca , Tenorio Jair , Perea Sofia , Medina Laura , Pazo-Cid Roberto , Juez Ignacio , Garcia-Carbonero Rocío , Feliu Jaime , Guillen-Ponce Carmen , Lopez-Casas Pedro P. , Guerra Carmen , Duran Yolanda , López-Acosta José Francisco , Alonso Carolina , Esquivel Estrella , Dopazo Ana , Akshinthala Dipikaa , Muthuswamy Senthil K. , Lapunzina Pablo , Bockorny Bruno , Hidalgo Manuel
Published: January 2025

Supplementary Table 2. Representativeness of Study Participants
Supplementary Table S3 from Re-Irradiation Plus Pembrolizumab: A Phase II Study for Patients with Recurrent Glioblastoma
Authors: Iwamoto Fabio M. , Tanguturi Shyam K. , Nayak Lakshmi , Wang Tony J. , Desai Arati , Lustig Robert A. , Bagley Stephen , Wong Eric T. , Hertan Lauren M. , McCluskey Christine , Hayden Julia , Muzikansky Alona , Nakhawa Shreya , Japo Julia , Bossi Connor C. , Meylan Maxime , Tian Ye , Barlow Graham L. , Speliakos Paul , Ayoub Georges , Meredith David M. , Ligon Keith L. , Haas-Kogan Daphne , Huang Kun , Wucherpfennig Kai W. , Wen Patrick Y. , Reardon David A.
Published: January 2025

Patient representativeness
Supplementary Table S2 from A First-in-Human Study of Cinrebafusp Alfa, a HER2/4-1BB Bispecific Molecule, in Patients with HER2-Positive Advanced Solid Malignancies
Authors: Piha-Paul Sarina , Olwill Shane A. , Hamilton Erika , Tolcher Anthony , Pohlmann Paula , Liu Stephen V. , Wurzenberger Cornelia , Hasenkamp Laura-Carolin , Hansbauer Eva-Maria , Shroff Rachna , Hurvitz Sara , Krishnamurthy Anuradha , Patnaik Amita , Hahn Noah , Kumar Raman , Duerr Manuela , Zettl Markus , Aviano Kayti , Matis Louis , Bruns Ingmar , Ku Geoffrey
Published: January 2025

Supplementary Table S2. Representativeness of Study Participants.
Supplementary Table S2 from Phase II Trial of Induction Chemotherapy for Advanced Sinonasal Squamous Cell Carcinoma
Authors: Contrera Kevin J. , Ferrarotto Renata , Gunn Brandon , Su Shirley Y. , Kies Merrill S. , Glisson Bonnie S. , Garden Adam S. , Roberts Dianna , Habna Curtis , Hoff Camilla O. , El-Naggar Adel , Williams Michelle D. , Raza Shaan M. , DeMonte Franco , Chen Melissa M. , Chambers Mark S. , Hanna Ehab Y.
Published: January 2025

Representativeness of Study Participants
Supplementary Figure S6 from Aberrant Activation of Wound-Healing Programs within the Metastatic Niche Facilitates Lung Colonization by Osteosarcoma Cells
Authors: Reinecke James B. , Jimenez Garcia Leyre , Gross Amy C. , Cam Maren , Cannon Matthew V. , Gust Matthew J. , Sheridan Jeffrey P. , Gryder Berkley E. , Dries Ruben , Roberts Ryan D.
Published: January 2025

Immediate vs delayed treatment, tumor burden-based randomization
Supplementary Figure S3 from Quantitative and Morphology-Based Deep Convolutional Neural Network Approaches for Osteosarcoma Survival Prediction in the Neoadjuvant and Metastatic Settings
Authors: Coudray Nicolas , Occidental Michael A. , Mantilla Jose G. , Claudio Quiros Adalberto , Yuan Ke , Balko Jan , Tsirigos Aristotelis , Jour George
Published: January 2025

Data distributions on the HPCs. A. Number of tiles associated with each HPC. B. Number of patients with at least 1, 5 or 50 tiles in each HPC. C. For each source institution, number of patients with at least one tile in each HPC. D. Number of tiles associated with each HPC, colored by type of disease (metastatic or primary). E. Same as D, but shown in terms of percentage of tiles associated with each HPC instead of absolute number of tiles. F. For type of disease, number of patients with at least one tile in each HPC.
Supplementary Data S1 from Quantitative and Morphology-Based Deep Convolutional Neural Network Approaches for Osteosarcoma Survival Prediction in the Neoadjuvant and Metastatic Settings
Authors: Coudray Nicolas , Occidental Michael A. , Mantilla Jose G. , Claudio Quiros Adalberto , Yuan Ke , Balko Jan , Tsirigos Aristotelis , Jour George
Published: January 2025

Per slide discrepancy between the necrosis/tumor ratio estimated manually vs by the AI.
Supplementary Figure S3 from A Phase II Open-Label, Randomized Clinical Trial of Atezolizumab with or without Human Recombinant IL-7 (CYT107) in Advanced Urothelial Cancer
Authors: Sweis Randy F. , Chatta Gurkamal S. , Jain Rohit K. , Moon Helen , Delacroix Scott Edward , Fang Alana , D’Amico Leonard , Kask Angela Shaulov , Cheever Martin A. , Fling Steven , Sharon Elad , Lacroix Andreanne , Kaiser Judith C. , Pachynski Russell K. , Yu Evan Y.
Published: January 2025

Pharmacodynamics of CD4+ (A) and CD8+ (B) T cell populations in the experimental arm showing fold-change from baseline of % of T lymphocyte subsets. Significant differences were most observed in the CD4+ effector memory T cell population.
Supplementary Figure S2 from A Phase II Open-Label, Randomized Clinical Trial of Atezolizumab with or without Human Recombinant IL-7 (CYT107) in Advanced Urothelial Cancer
Authors: Sweis Randy F. , Chatta Gurkamal S. , Jain Rohit K. , Moon Helen , Delacroix Scott Edward , Fang Alana , D’Amico Leonard , Kask Angela Shaulov , Cheever Martin A. , Fling Steven , Sharon Elad , Lacroix Andreanne , Kaiser Judith C. , Pachynski Russell K. , Yu Evan Y.
Published: January 2025

Kaplan-Meier Curve for Overall Survival - All Randomized Subjects.
Supplementary Figure S1 from A Phase II Open-Label, Randomized Clinical Trial of Atezolizumab with or without Human Recombinant IL-7 (CYT107) in Advanced Urothelial Cancer
Authors: Sweis Randy F. , Chatta Gurkamal S. , Jain Rohit K. , Moon Helen , Delacroix Scott Edward , Fang Alana , D’Amico Leonard , Kask Angela Shaulov , Cheever Martin A. , Fling Steven , Sharon Elad , Lacroix Andreanne , Kaiser Judith C. , Pachynski Russell K. , Yu Evan Y.
Published: January 2025

Kaplan-Meier Curve for Progression Free Survival as measured by RECIST v1.1 - All Randomized Subjects.
Supplementary Table S1 from A Tumor-Naïve ctDNA Assay Detects Minimal Residual Disease in Resected Stage II or III Colorectal Cancer and Predicts Recurrence: Subset Analysis from the GALAXY Study in CIRCULATE-Japan
Authors: Nakamura Yoshiaki , Kaneva Kristiyana , Lo Christine , Neems Daniel , Freaney Jonathan E. , Boulos Hala , Hyun Seung Won , Islam Farahnaz , Yamada-Hanff Jason , Driessen Terri M. , Sonnenschein Anne , DeSantis Dana F. , Kotani Daisuke , Watanabe Jun , Kotaka Masahito , Mishima Saori , Bando Hideaki , Yamazaki Kentaro , Taniguchi Hiroya , Takemasa Ichiro , Kato Takeshi , Sangli Chithra , Tell Robert , Blidner Richard , Yoshino Takayuki , Sasser Kate , Oki Eiji , Nimeiri Halla
Published: January 2025

Table S1. MRD call definitions
Supplementary Table S5 from Phase Ib Clinical and Pharmacodynamic Study of the TIE2 Kinase Inhibitor Rebastinib with Paclitaxel or Eribulin in HER2-Negative Metastatic Breast Cancer
Authors: Anampa Jesus D. , Flynn Daniel L. , Leary Cynthia , Oh Sun , Xue Xiaonan , Oktay Maja H. , Condeelis John S. , Sparano Joseph A.
Published: January 2025

Supplementary Table S5 shows Treatment Related Adverse Events (TRAE) by chemotherapy and rebastinib dose (n = 27).
Supplementary Figure S2 from A Tumor-Naïve ctDNA Assay Detects Minimal Residual Disease in Resected Stage II or III Colorectal Cancer and Predicts Recurrence: Subset Analysis from the GALAXY Study in CIRCULATE-Japan
Authors: Nakamura Yoshiaki , Kaneva Kristiyana , Lo Christine , Neems Daniel , Freaney Jonathan E. , Boulos Hala , Hyun Seung Won , Islam Farahnaz , Yamada-Hanff Jason , Driessen Terri M. , Sonnenschein Anne , DeSantis Dana F. , Kotani Daisuke , Watanabe Jun , Kotaka Masahito , Mishima Saori , Bando Hideaki , Yamazaki Kentaro , Taniguchi Hiroya , Takemasa Ichiro , Kato Takeshi , Sangli Chithra , Tell Robert , Blidner Richard , Yoshino Takayuki , Sasser Kate , Oki Eiji , Nimeiri Halla
Published: January 2025

Figure S2. MRD status over time in non-recurrent study participants
Supplementary Figure S9 from Phase Ib Clinical and Pharmacodynamic Study of the TIE2 Kinase Inhibitor Rebastinib with Paclitaxel or Eribulin in HER2-Negative Metastatic Breast Cancer
Authors: Anampa Jesus D. , Flynn Daniel L. , Leary Cynthia , Oh Sun , Xue Xiaonan , Oktay Maja H. , Condeelis John S. , Sparano Joseph A.
Published: January 2025

Supplementary Figure S9 shows progression-free survival (PFS) in all patients (A) and stratified by treatment (B). Abbreviations: E, eribulin; P, paclitaxel; R, rebastinib.
Supplementary Figure S8 from Phase Ib Clinical and Pharmacodynamic Study of the TIE2 Kinase Inhibitor Rebastinib with Paclitaxel or Eribulin in HER2-Negative Metastatic Breast Cancer
Authors: Anampa Jesus D. , Flynn Daniel L. , Leary Cynthia , Oh Sun , Xue Xiaonan , Oktay Maja H. , Condeelis John S. , Sparano Joseph A.
Published: January 2025

Supplementary Figure S8 shows the effect of chemotherapy or rebastinib on TIE2 monocytes. A, Trends in TIE2 monocytes with rebastinib and rebastinib plus chemotherapy; B, trends in TIE2 monocytes with chemotherapy and rebastinib plus chemotherapy. Each line represent data from one patient over time. Abbreviations: C, Cycle; D, Day.
Supplementary Tables 1 from Divergent Clinical and Immunologic Outcomes Based on STK11 Co-mutation Status in Resectable KRAS-Mutant Lung Cancers Following Neoadjuvant Immune Checkpoint Blockade
Authors: Rosner Samuel , Connor Sydney , Sanber Khaled , Zahurak Marianna , Zhang Tianbei , Gurumurthy Isha , Zeng Zhen , Presson Brad , Singh Dipika , Rayes Roni , Sivapalan Lavanya , Pereira Gavin , Ji Zhicheng , Thummalapalli Rohit , Reuss Joshua E. , Broderick Stephen R. , Jones David R. , Deutsch Julie S. , Cottrell Tricia R. , Chaft Jamie E. , Spicer Jonathan , Taube Janis , Anagnostou Valsamo , Brahmer Julie R. , Pardoll Drew M. , Ji Hongkai , Forde Patrick M. , Marrone Kristen A. , Smith Kellie N.
Published: January 2025

Tables S1-S4
Supplementary Figure S3 from Phase Ib Clinical and Pharmacodynamic Study of the TIE2 Kinase Inhibitor Rebastinib with Paclitaxel or Eribulin in HER2-Negative Metastatic Breast Cancer
Authors: Anampa Jesus D. , Flynn Daniel L. , Leary Cynthia , Oh Sun , Xue Xiaonan , Oktay Maja H. , Condeelis John S. , Sparano Joseph A.
Published: January 2025

Supplementary Figure S3 shows Change in angiopoietin 1 levels (%) after 2 cycles of therapy. The length of each bar represents individual decrease or increase in a biomarker after 2 cycles of therapy.
Supplementary Figure S1 from Phase Ib Clinical and Pharmacodynamic Study of the TIE2 Kinase Inhibitor Rebastinib with Paclitaxel or Eribulin in HER2-Negative Metastatic Breast Cancer
Authors: Anampa Jesus D. , Flynn Daniel L. , Leary Cynthia , Oh Sun , Xue Xiaonan , Oktay Maja H. , Condeelis John S. , Sparano Joseph A.
Published: January 2025

Supplementary Figure S1 shows Study flow diagram of dose escalation and expansion cohort.
Data from Hormone Receptor–Positive HER2-Negative/MammaPrint High-2 Breast Cancers Closely Resemble Triple-Negative Breast Cancers
Authors: Rios-Hoyo Alejandro , Xiong Kaitlyn , Dai Jiawei , Yau Christina , Marczyk Michal , Garcia-Milian Rolando , Wolf Denise M. , Huppert Laura A. , Nanda Rita , Hirst Gillian L. , Cobain Erin F. , van ’t Veer Laura J. , Esserman Laura J. , Pusztai Lajos
Published: January 2025

AbstractPurpose:
The MammaPrint (MP) prognostic assay categorizes breast cancers into high- and low-risk subgroups, and the high-risk group can be further subdivided into high-1 (MP-H1), and very high-risk high-2 (MP-H2). The aim of this analysis was to assess clinical and molecular differences between the hormone receptor–positive (HR+)/HER2-negative MP-H1, -H2, and triple-negative (TN) MP-H1 and -H2 cancers.
Experimental Design:
Pretreatment gene expression data from 742 HER2-negative breast cancers enrolled in the I-SPY2 neoadjuvant trial were used. Prognostic risk categories were assigned using the MP assay. Transcriptional similarities across the four receptor and prognostic groups were assessed using principal component analyses and by identifying differentially expressed genes. We also examined pathologic complete response rates and event-free survivals by risk group.
Results:
Principal component analysis showed that HR+/MP-H2 tumors clustered with TN/MP-H2 cancers. Only 125 genes showed differential expression between the HR+/MP-H2 and TN/MP-H2 cancers, whereas 1,465 genes were differentially expressed between HR+/MP-H2 and -H1. Gene set analysis revealed similarly high expression of cell cycle, DNA repair, and immune infiltration–related pathways in HR+/MP-H2 and TN/MP-H2 cancers. HR+/MP-H2 cancers also showed low estrogen receptor–related gene expression. Pathologic complete response rates were similarly high in TN/MP-H2 and HR+/MP-H2 cancers (42% vs. 30.5%; P = 0.11), and MP-H2 cancers with residual cancer had similarly poor event-free survival regardless of estrogen receptor status.
Conclusions:
In conclusion, HR+/MP-H2 cancers closely resemble TN breast cancers in transcriptional and clinical features and benefit from similar treatment strategies.
Data from Re-Irradiation Plus Pembrolizumab: A Phase II Study for Patients with Recurrent Glioblastoma
Authors: Iwamoto Fabio M. , Tanguturi Shyam K. , Nayak Lakshmi , Wang Tony J. , Desai Arati , Lustig Robert A. , Bagley Stephen , Wong Eric T. , Hertan Lauren M. , McCluskey Christine , Hayden Julia , Muzikansky Alona , Nakhawa Shreya , Japo Julia , Bossi Connor C. , Meylan Maxime , Tian Ye , Barlow Graham L. , Speliakos Paul , Ayoub Georges , Meredith David M. , Ligon Keith L. , Haas-Kogan Daphne , Huang Kun , Wucherpfennig Kai W. , Wen Patrick Y. , Reardon David A.
Published: January 2025

AbstractPurpose:
Radiotherapy may enhance antitumor immune responses by several mechanisms, including induction of immunogenic cell death. We performed a phase 2 study of pembrolizumab with re-irradiation in patients with recurrent glioblastoma.
Patients and Methods:
Sixty patients with recurrent glioblastoma received pembrolizumab with re-irradiation alone (cohort A, bevacizumab-naïve; n = 30) or with bevacizumab continuation (cohort B, n = 30). Dual primary endpoints, including the overall response rate and overall survival (OS) at either 12 (OS-12; cohort A) or 6 months (OS-6; cohort B), were assessed per cohort relative to historic benchmarks. Paired paraffin-embedded formalin-fixed tumor samples were assessed for immunologic biomarkers by IHC using digital quantification and co-detection-by-indexing (CODEX).
Results:
Study therapy was well tolerated, with most toxicities being grade ≤3. For cohort B, the primary endpoint of OS-6 was achieved (57%); however, survival was not improved for cohort A patients. The overall response rate was 3.3% and 6.7% for cohorts A and B, respectively. CODEX analysis of paired tumor samples from five patients revealed an increase of activated T cells in the tumor microenvironment after study therapy.
Conclusions:
Compared with historic controls, re-irradiation plus pembrolizumab seemed to improve survival among bevacizumab-refractory patients but not among bevacizumab-naïve patients. CODEX revealed evidence of intratumoral infiltration of activated immune effector cells. A randomized, properly controlled trial of PD-1 blockade plus re-irradiation is warranted to further evaluate this regimen for bevacizumab-refractory patients, but alternative approaches are needed for bevacizumab-naïve patients.
Data from Analysis of Shared Variants between Cancer Biospecimens
Authors: Foote Michael B. , White James Robert , Chatila Walid K. , Argilés Guillem , Lu Steve , Rousseau Benoit , Artz Oliver , Johannet Paul , Walch Henry , Patel Mitesh , Lamendola-Essel Michelle F. , Casadevall David , Abdelfattah Somer , Patel Shrey , Yaeger Rona , Cercek Andrea , Montagut Clara , Berger Michael , Schultz Nikolaus , Diaz Luis A.
Published: January 2025

AbstractPurpose:
Mutational data from multiple solid and liquid biospecimens of a single patient are often integrated to track cancer evolution. However, there is no accepted framework to resolve if individual samples from the same individual share variants due to common identity versus coincidence.
Experimental Design:
Utilizing 8,000 patient tumors from The Cancer Genome Atlas across 33 cancer types, we estimated the background rates of co-occurrence of mutations between discrete pairs of samples across cancers and by cancer type. We developed a mutational profile similarity (MPS) score that uses a large background database to produce confidence estimates that two tumors share a unique, related molecular profile. The MPS algorithm was applied to randomly paired tumor profiles, including patients who underwent repeat solid tumor biopsies sequenced with Memorial Sloan Kettering-IMPACT (n = 53,113). We also evaluated the MPS in sample pairs from single patients with multiple cancers (n = 2,012), as well as patients with plasma and solid tumor variant profiles (n = 884 patients).
Results:
In unrelated tumors, nucleotide-specific variants are shared in 1.3% (cancer-type agnostic) and in 10% to 13% (cancer-type specific) of cases. The MPS method contextualized shared variants to specify whether patients had a single cancer versus multiple distinct cancers. When multiple tumors were compared from the same patient and an initial clinicopathologic diagnosis was discordant with molecular findings, the MPS anticipated future diagnosis changes in 28% of examined cases.
Conclusions:
The use of a novel shared variant framework can provide information to clarify the molecular relationship between compared biospecimens with minimal required input.
Data from Aberrant Activation of Wound-Healing Programs within the Metastatic Niche Facilitates Lung Colonization by Osteosarcoma Cells
Authors: Reinecke James B. , Jimenez Garcia Leyre , Gross Amy C. , Cam Maren , Cannon Matthew V. , Gust Matthew J. , Sheridan Jeffrey P. , Gryder Berkley E. , Dries Ruben , Roberts Ryan D.
Published: January 2025

AbstractPurpose:
Lung metastasis is responsible for nearly all deaths caused by osteosarcoma, the most common pediatric bone tumor. How malignant bone cells coerce the lung microenvironment to support metastatic growth is unclear. The purpose of this study is to identify metastasis-specific therapeutic vulnerabilities by delineating the cellular and molecular mechanisms underlying osteosarcoma lung metastatic niche formation.
Experimental Design:
Using single-cell RNA sequencing, we characterized genome- and tissue-wide molecular changes induced within lung tissues by disseminated osteosarcoma cells in both immunocompetent murine models of metastasis and patient samples. We confirmed transcriptomic findings at the protein level and determined spatial relationships with multiparameter immunofluorescence and spatial transcriptomics. Based on these findings, we evaluated the ability of nintedanib, a kinase inhibitor used to treat patients with pulmonary fibrosis, to impair metastasis progression in both immunocompetent murine osteosarcoma and immunodeficient human xenograft models. Single-nucleus and spatial transcriptomics were used to perform molecular pharmacodynamic studies that define the effects of nintedanib on tumor and nontumor cells within the metastatic microenvironment.
Results:
Osteosarcoma cells induced acute alveolar epithelial injury upon lung dissemination. Single-cell RNA sequencing demonstrated that the surrounding lung stroma adopts a chronic, nonresolving wound-healing phenotype similar to that seen in other models of lung injury. Accordingly, the metastasis-associated lung demonstrated marked fibrosis, likely because of the accumulation of pathogenic, profibrotic, partially differentiated epithelial intermediates and macrophages. Our data demonstrated that nintedanib prevented metastatic progression in multiple murine and human xenograft models by inhibiting osteosarcoma-induced fibrosis.
Conclusions:
Fibrosis represents a targetable vulnerability to block the progression of osteosarcoma lung metastasis. Our data support a model wherein interactions between osteosarcoma cells and epithelial cells create a prometastatic niche by inducing tumor deposition of extracellular matrix proteins such as fibronectin that is disrupted by the antifibrotic tyrosine kinase inhibitor (TKI) nintedanib. Our data shed light on the non–cell-autonomous effects of TKIs on metastasis and provide a roadmap for using single-cell and spatial transcriptomics to define the mechanism of action of TKI on metastases in animal models.
Data from Clinical Pharmacology of Cytokine Release Syndrome with T-Cell–Engaging Bispecific Antibodies: Current Insights and Drug Development Strategies
Authors: Radtke Kendra K. , Bender Brendan C. , Li Zao , Turner David C. , Roy Sumedha , Belousov Anton , Li Chi-Chung
Published: January 2025

Abstract
Cytokine release syndrome (CRS) is a common acute toxicity in T-cell therapies, including T-cell–engaging bispecific antibodies (T-BiSp). Effective CRS management and prevention are crucial in T-BiSp development. Required hospitalization for seven of the nine approved T-BiSp and the need for clinical intervention in severe cases highlight the importance of mitigation strategies to reduce health care burden and improve patient outcomes. In this review, we discuss the emerging evidence on CRS mitigation, management, and prediction. We cover different strategies for dose optimization, current and emerging (pre) treatment strategies, quantitative pharmacology tools used during drug development, and biomarkers and predictive factors. Insights are gleaned on step-up dosing and formulation effects on CRS and CRS relationships with cytokine dynamics and drug levels gathered through a review of T-BiSp licensing applications and emerging data from conferences and publications.