bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 related disruption and resilience in immunisation activities in LMICs: a rapid review
Authors: Hartner Anna-Maria , Li Xiang , Gaythorpe Katy
Published: August 2024

Objectives

We conducted a rapid review to determine the extent that immunisation services in low-income and middle-income countries (LMICs) were disrupted by the COVID-19 pandemic and synthesised the factors that can be used to build resilience in future.

Design

Rapid review reported in accordance with the Preferred reporting for Systematic reviews and Meta-Analyses (PRISMA) guidelines.

Data sources

PubMed and Web of Science were searched through 6 October 2023.

Eligibility criteria for selecting studies

We included studies that focused on disruption to immunisation activities due to the COVID-19 pandemic in LMICs. Outcomes included routine vaccine coverage, supplementary immunisation activities, vaccine doses, timing of vaccination, supply chain changes, and factors contributing to disruption or resilience.

Data extraction and synthesis

Two independent reviewers used standardised methods to search, screen and code studies. Quality assessment was performed using a modified version of the Critical Appraisal Skills Programme for qualitative research. Findings were summarised qualitatively.

Results

Of 4978 identified studies, 85 met the eligibility criteria. Included studies showed declines in immunisation activities across LMICs related to the COVID-19 pandemic. These included reductions in achieved routine coverage, cancellation or postponement of campaigns and underimmunised cohorts. Immunisation was most disrupted in the early months of the pandemic; however, recovery varied by country, age-group and vaccine. Though many countries observed partial recovery in 2020, disruption in many countries continued into 2021. It has also been noted that clinician staff shortages and vaccine stock-outs caused by supply chain disruptions contributed to immunisation delays, but that concern over COVID-19 transmission was a leading factor. Key resiliency factors included community outreach and healthcare worker support.

Conclusions

There is limited information on whether reductions in vaccination coverage or delays have persisted beyond 2021. Further research is needed to assess ongoing disruptions and identify missed vaccine cohorts.
Effects of the intermittent theta burst stimulation on gait, balance and lower limbs motor function in stroke: study protocol for a double-blind randomised controlled trial with multimodal neuroimaging assessments
Authors: Huang Guilan , Wang Hewei , Zhao WeiWei , Qian Yao , Yao Yu , Zhang Li , Chen Yating , Song Lianxin , Yang Jinyu , Liu Zhichao , Su Bin , Sun Limin
Published: August 2024

Introduction

Approximately, 50% of stroke survivors experience impaired walking ability 6 months after conventional rehabilitation and standard care. However, compared with upper limb motor function, research on lower limbs rehabilitation through non-invasive neuromodulation like repetitive transcranial magnetic stimulation (rTMS) has received less attention. Limited evidence exists regarding the effectiveness of intermittent theta-burst stimulation (iTBS), an optimised rTMS modality, on lower limbs rehabilitation after stroke. This study aims to evaluate the effects of iTBS on gait, balance and lower limbs motor function in stroke recovery while also exploring the underlying neural mechanisms using longitudinal analysis of multimodal neuroimaging data.

Methods and analysis

In this double-blinded randomised controlled trial, a total of 46 patients who had a stroke will be randomly assigned in a 1:1 ratio to receive either 15 sessions of leg motor area iTBS consisting of 600 pulses or sham stimulation over the course of 3 weeks. Additionally, conventional rehabilitation therapy will be administered following the (sham) iTBS intervention. The primary outcome measure will be the 10 m walking test. Secondary outcomes include the Fugl-Meyer assessment of the lower extremity, Timed Up and Go Test, Functional Ambulation Category Scale, Berg Balance Scale, modified Barthel Index, Mini-Mental State Examination, montreal cognitive assessment, tecnobody balance assessment encompassing both static and dynamic stability evaluations, surface electromyography recording muscle activation of the lower limbs, three-dimensional gait analysis focusing on temporal and spatial parameters as well as ground reaction force measurements, corticomotor excitability tests including resting motor threshold, motor evoked potential and recruitment curves and multimodal functional MRI scanning. Outcome measures will be collected prior to and after the intervention period with follow-up at 3 weeks.

Ethics and dissemination

The study has received approval from the Medical Research Ethics Committee of Wuxi Mental Health Center/Wuxi Central Rehabilitation Hospital (no. WXMHCCIRB2023LLky078). Results will be disseminated through peer-reviewed journals and scientific conferences.

Trial registration number

ChiCTR2300077431.
Compressing the two-particle Green’s function using wavelets: Theory and application to the Hubbard atom
Authors: Moghadas Emin , Dräger Nikolaus , Toschi Alessandro , Zang Jiawei , Medvidović Matija , Kiese Dominik , Millis Andrew J. , Sengupta Anirvan M. , Andergassen Sabine , Di Sante Domenico
Published: August 2024

Precise algorithms capable of providing controlled solutions in the presence of strong interactions are transforming the landscape of quantum many-body physics. Particularly, exciting breakthroughs are enabling the computation of non-zero temperature correlation functions. However, computational challenges arise due to constraints in resources and memory limitations, especially in scenarios involving complex Green’s functions and lattice effects. Leveraging the principles of signal processing and data compression, this paper explores the wavelet decomposition as a versatile and efficient method for obtaining compact and resource-efficient representations of the many-body theory of interacting systems. The effectiveness of the wavelet decomposition is illustrated through its application to the representation of generalized susceptibilities and self-energies in a prototypical interacting fermionic system, namely the Hubbard model at half-filling in its atomic limit. These results are the first proof-of-principle application of the wavelet compression within the realm of many-body physics and demonstrate the potential of this wavelet-based compression scheme for understanding the physics of correlated electron systems.
Robust estimation and test for Pearson’s correlation coefficient
Authors: Liu Pengfei , Wang Shaochen , Zhao Peng
Published: August 2024

In this paper, using the idea of grouping under moderate data framework, we propose the median-of-means-type nonparametric estimator for Pearson’s correlation coefficient which has been used widely in various disciplines. Under certain conditions on the growing rate of the number of subgroups, the consistency and asymptotic normality of the proposed estimator are investigated. Furthermore, we construct a new method to test Pearson’s correlation coefficient based on the empirical likelihood method for median. Extensively numerical simulations are designed to demonstrate the superiorities of our estimator. It is shown that the new proposed estimator is robust with respect to outliers. Finally, we use the proposed method to study Pearson’s correlation between open price and the rate of price spread for the Shanghai Stock Exchange composite index from 18 May 2015 to 21 June 2019.
Letter from the Chair
Authors: Murdock Vanessa
Published: August 2024

Greetings SIGIR Members! Preparations for SIGIR 2024 and ICTIR 2024 in Washington DC are nearing completion, as preparations for SIGIR-AP in Tokyo in December are underway, and CHIIR, ICTIR and SIGIR conferences in 2025 are starting up. The SIGIR Academy Class of 2024 has been announced. The award recognizes individuals who have made significant, cumulative contributions to the development of the field of information retrieval. Inductees are principal leaders in IR, whose efforts have shaped the discipline through significant research, innovation, and service. We would like to congratulate the newest members:
Fernando Diaz, Donna Harman, Mounia Lalmas, Mark Sanderson, and Yiqun Liu.
Report on the 1st International Workshop on Graph-Based Approaches in Information Retrieval (IRonGraphs 2024) at ECIR 2024
Authors: Boratto Ludovico , Malitesta Daniele , Marras Mirko , Medda Giacomo , Musto Cataldo , Purificato Erasmo
Published: August 2024

The First International Workshop on Graph-Based Approaches in Information Retrieval (IRonGraphs 2024) was held as a physical (in-person) event on March 24, 2024, in conjunction with the 46th European Conference on Information Retrieval (ECIR 2024) in Glasgow (Scotland). The scientific program included paper, spotlight, and poster presentations. Two keynote talks were delivered by Francesco Fabbri (Spotify, Spain) and Ruihong Qiu (University of Queensland, Australia). This report presents an overview of the activities conducted during the workshop and the main topics covered.

Date
: 24 March 2024.

Website
: https://irongraphs.github.io/ecir2024/.
Report on the 19th French Conference on Information Retrieval and Applications (CORIA 2024)
Authors: Ermakova Liana , Mulhem Philippe , Doucet Antoine , Gonzalez-Gallardo Carlos-Emiliano , Fournier Sébastien
Published: August 2024

We present here a short report on the French Information Retrieval Conference CORIA 2024, held in La Rochelle, France, on the 3rd and 4th of April 2024. We describe the objectives of the CORIA and provide an overview of the event, the submissions, and the keynotes.

Date
: 3--4 April 2024.

Website
: http://coria.asso-aria.org/2024/.
Software Optimization and Design Methodology for Low Power Computer Vision Systems
Authors: Ha Soonhoi , Jeong Eunjin
Published: August 2024

This tutorial article addresses a low power computer vision system as an example of a growing application domain of neural networks, exploring various technologies developed to enhance accuracy within the resource and performance constraints imposed by the hardware platform. Focused on a given hardware platform and network model, software optimization techniques, including pruning, quantization, low-rank approximation, and parallelization, aim to satisfy resource and performance constraints while minimizing accuracy loss. Due to the interdependence of model compression approaches, their systematic application is crucial, as evidenced by winning solutions in the Lower Power Image Recognition Challenge (LPIRC) of 2017 and 2018. Recognizing the typical heterogeneity of processing elements in contemporary hardware platforms, the effective utilization through parallelizing neural networks emerges as increasingly vital for performance enhancement. The article advocates for a more impactful strategy—designing a network architecture tailored to a specific hardware platform. For detailed information on each technique, the article provides corresponding references.
A Guided Tour of Phylogenetic Comparative Methods for Studying Trait Evolution
Authors: Cornwallis Charlie K. , Griffin Ashleigh S.
Published: August 2024

Phylogenetic comparative methods are important tools in biology, providing insights into the way traits evolve. There are many technical resources describing how these methods work. Our aim here is to complement these with an overview of the types of biological questions that can be addressed by different methods and to outline potential pitfalls and considerations when embarking on comparative studies. First, we introduce what comparative methods are and why they are important. Second, we outline how they can be used to understand when, where, and how frequently traits evolve. Third, we examine how the coevolution of traits within and between species can be studied, along with patterns of causality. Finally, we discuss how to approach comparative analyses and the ways in which different types of data, such as published relationships, omic, and remote sensing data, can be integrated.
Volatile Organic Compound Emissions in the Changing Arctic
Authors: Rinnan Riikka
Published: August 2024

Arctic ecosystems have long been thought to be minimal sources of volatile organic compounds (VOCs) to the atmosphere because of their low plant biomass and cold temperatures. However, these ecosystems experience rapid climatic warming that alters vegetation composition. Tundra vegetation VOC emissions have stronger temperature dependency than current emission models estimate. Thus, warming, both directly and indirectly (via vegetation changes) likely increases the release and alters the blend of emitted plant volatiles, such as isoprene, monoterpenes, and sesquiterpenes, from Arctic ecosystems. Climate change also increases the pressure of both background herbivory and insect outbreaks. The resulting leaf damage induces the production of volatile defense compounds, and warming amplifies this response. Soils function as both sources and sinks of VOCs, and thawing permafrost is a hotspot for soil VOC emissions, contributing to ecosystem emissions if the VOCs bypass microbial uptake. Overall, Arctic VOC emissions are likely to increase in the future, with implications for ecological interactions and atmospheric composition.
What Gets Shared, and Why? Interpersonal Communication and Word of Mouth
Authors: Berger Jonah
Published: August 2024

Interpersonal communication is an integral part of everyday life. People are constantly sharing thoughts, opinions, and information with others, both online and offline. Further, such social sharing has important implications for what people think, buy, and do. However, while it is clear that interpersonal communication is both frequent and important, research is only starting to understand what people share and why. This article reviews the literature on interpersonal communication and word of mouth, focusing on the drivers of social transmission and the implications for individuals and society at large. It discusses how factors like audiences, modalities (e.g., speaking or writing), channels (e.g., email or text), and devices (e.g., phone or PC) moderate what gets shared, and it outlines areas that deserve further attention. Such areas include the diffusion of false information, conversations and conversational dynamics, and how automated textual analysis can be used to shed light on a range of interesting questions.
Delayed and diminished postprandial lactate shuttling in healthy older men and women
Authors: Arevalo Jose A. , Leija Robert G. , Osmond Adam D. , Curl Casey C. , Duong Justin J. , Huie Melvin J. , Masharani Umesh , Brooks George A.
Published: August 2024

We used isotope tracers, an oral glucose tolerance test, and arterialized blood sampling to determine postprandial lactate flux rates in healthy young and older men and women. Lactate rates of appearance and oxidation and the lactate‐pyruvate exchange were delayed and diminished in both enteric and systemic postprandial lactate shuttle phases in older participants.
Does a single oral administration of amiloride affect spontaneous arterial baroreflex sensitivity and blood pressure variability in healthy young adults?
Authors: Fernandes Igor A. , Stavres Jon , Hamaoka Takuto , Ojikutu Qudus A. , Sabino-Carvalho Jeann L. , Vianna Lauro C. , Luck J. Carter , Blaha Cheryl , Cauffman Aimee E. , Dalton Paul C. , Herr Michael D. , Ruiz-Velasco Victor , Carr Zyad J. , Janicki Piotr K. , Cui Jian
Published: August 2024

Preclinical models indicate that amiloride (AMD), a nonselective antagonist of the acid-sensing ion channels (ASICs), impairs baroreflex sensitivity and perturbs blood pressure regulation. We translated these findings into humans, investigating the impact of acute oral ingestion of AMD on blood pressure variability and spontaneous cardiac and sympathetic baroreflex sensitivity in healthy young humans. In contrast to preclinical evidence, AMD does not impair spontaneous arterial baroreflex sensitivity and blood pressure variability in healthy young adults.
ANN‐Enhanced Energy Reference Models for Industrial Buildings: Multinational Company Case Study
Authors: Ouaomar Younes , Benkechcha Said , Kaddiri Mourad
Published: August 2024

This paper established a novel approach for developing simplified yet accurate models using artificial neural networks (ANNs) in industrial environments. It demonstrates that combining nonlinear regression with neural network modeling enhances predictive accuracy while maintaining the inherent simplicity of ANNs. Industrial sectors are increasingly adopting environmentally friendly practices, driven by the recognition that sustainable initiatives can lead to significant and lasting financial benefits rather than merely a sense of ecological duty. Integrating energy efficiency practices offers potential advantages in waste reduction and resource conservation, which can decrease operating expenses over time. This contributes significantly to pollution mitigation by reducing overall energy consumption cost‐effectively. Numerical simulations based on experimental results validate the proposed method, addressing the complexity and accuracy challenges in business models within the energy sector.
Investigation of the Economic Mechanism of Utilizing Distributed Solar Photovoltaic Systems in Iran
Authors: Labbafi Sana , Labbafi Sina , Heirani Hossein , Sina Seyedali
Published: August 2024

Today, the utilization of small‐scale solar systems for houses has increased significantly around the globe. The rise of electricity prices due to elevated prices of fossil fuels coupled with the global concerns about the increased emission of greenhouse gases has fueled the increased application of renewable energy systems. However, such policies have been ineffective in particular countries where the electricity prices are kept too low to control social atmosphere and enhance the people’s well‐being for political purposes—in this case, solar systems have witnessed no growth as they have rendered not economically justifiable. In this respect, the present research considers Iran as a country with very low electricity prices coupled with very large potentials for utilizing solar energy in the presence of imbalanced electricity supply and demand, with the research objective being an investigation of the required incentive policies to promote the utilization of distributed solar photovoltaic (DSPV) systems in the country. According to the results, it was figured out that, under the current conditions, escalating the price of electricity for houses (even to as high as 10 times the current prices) cannot cover the costs of the equivalent DSPV systems, indicating a need for another cluster of policies. As an option, one may consider buying the generated electricity by the customer (from renewable sources) at a higher price than that at which the electricity is offered to households via the grid (by a margin of 15 folds), which is supposed to provide the required incentive to expand the utilization of DSPV systems.
Prevalence and Associated Factors of Adolescent (15–19 Years) Childbearing in Ghana
Authors: Alhassan Abdul Rauf , Wepeba Tina Wepeamo , Abdulai Kasim , Iddrisu Rhubamatu , Aninanya Gifty Apiung
Published: August 2024

Background: Adolescent pregnancies continue to be a global issue that affects more high‐income, middle‐income, and then low‐income countries, with the latter experiencing the majority of cases.

Aim: The current study looked into the prevalence and variables predicting adolescent childbearing in Ghana.

Methodology: Data from the Ghana Multiple Indicator Cluster Survey (MICS) 2017–2018 was used to conduct an analytical cross‐sectional study. The results were examined with SPSS Version 20 (IBM Corp., 2011, and NY). Pearson’s chi‐square and binary logistics analyses were done for associations. A p value of 0.05 was used to determine the analysis’s statistical significance.

Results: The total number of adolescents isolated from the 2017 Ghana MICS dataset for this study analysis was 2974. The mean age of the study participants was 16.9 ± 1.4 years with a modal age of 15 years. The prevalence of adolescent childbearing according to this study analysis was 12.3%. The predictive factors for adolescent childbearing were increasing age, decreasing educational level, Volta regional originality, ethnic originality of the study participants, and low economic status.

Conclusion: The prevalence of adolescent childbearing in this study was significant and needs the attention of all. Programs to improve adolescent reproductive health must take into account multiple levels of elements, such as the individual, family, community, institutions, national, and international challenges that have an impact on such programs.
Significant Association of PD‐L1 With CD44 Expression and Patient Survival: Avenues for Immunotherapy and Cancer Stem Cells Downregulation in Pancreatic Cancers
Authors: Ali Saleema Mehboob , Adnan Yumna , Ahmad Zubair , Chawla Tabish , Ali S. M. Adnan
Published: August 2024

Background: Pancreatic cancers are known for their aggressive nature. This aggressiveness may be attributed to the presence of cancer stem cells (CSCs), which promote relapse, metastasis, and resistance to chemotherapy. Targeting CSCs is essential to reverse this aggressiveness in pancreatic malignancies. Literature highlights the association of PD‐L1 expression with CSCs in various cancers, suggesting immunotherapy as a promising therapeutic approach. This study is aimed at investigating the potential of immunotherapy in pancreatic cancers by examining its association with selected CSC marker expression.

Method: A retrospective cohort study was conducted involving 56 patients with confirmed diagnoses of pancreatic cancers at Aga Khan University Hospital from January 2015 to October 2022. After exclusions, based on refusal to provide consent or incomplete follow‐up data, 38 patients were enrolled in the study. Immunohistochemistry was performed on formalin‐fixed paraffin‐embedded (FFPE) tumor tissue samples to assess the expression of CSC markers (CD133, CD44, and L1CAM) and immune checkpoint inhibitor marker (PD‐L1). Statistical analysis was employed to determine associations between marker expression, clinical factors, and overall survival.

Results: The study revealed that 86.8% of pancreatic cancer cases exhibited positive PD‐L1 expression. Moreover, a significant association of PD‐L1 expression was observed with the presence of CD44 protein (p = 0.030), as well as with the overall survival of patients (p = 0.023).

Conclusion: Our findings show a significant association of PD‐L1 with CD44 marker expression as well as patient survival. This research shows the potential to serve as the foundation for investigating the efficacy of immunotherapy in reducing CD44‐expressing CSCs in pancreatic cancer, potentially enhancing patient outcomes.
Prevalence of Self‐Medication Practice and Associated Factors among Pregnant Women Who Attended Antenatal Care at Public Hospitals of North Shewa Zone, Amhara Region, Ethiopia
Authors: Demis Abrham , Altaye Birhanetensay Masresha , Emiru Mulugeta , Tefera Mitiku
Published: August 2024

Background. Self‐medication practice is the use of medicine without consulting health professionals to treat self‐recognized illness by the general population including pregnant women. Inappropriate self‐medication practice during pregnancy may pose harmful consequences for the fetus as well as the mother. There is not given much attention on the practice of self‐medication among pregnant women in our setting. Therefore, this study aimed to assess the prevalence of self‐medication practice and associated factors among pregnant women who attended antenatal care at North Shewa Zone public hospitals. Methods. An institution‐based cross‐sectional study was conducted from June 01, 2022 to July 30, 2022, among 650 pregnant women who attended antenatal care at North Shewa Zone public hospitals. A multistage sampling technique was employed. The questionnaires were pretested. A structured interviewer‐administered questionnaire and reviewed medical records were used for data collection. Epi‐data version 4.6.2 and SPSS version 20 were utilized for data entry and analysis, respectively. Bivariate and multivariable logistic regression was done to identify associated factors, and P values less than 0.05 were considered statistically significant. Results. The prevalence of self‐medication practice among pregnant women was 65.38%. Housewives (AOR = 0.097 95% CI 0.030, 0.310), farmers (AOR = 0.117, 95% CI 0.028, 0.493), people with health insurance (AOR = 0.507, 95% CI 0.300, 0.858), and people in preconception care (AOR = 0.038, 95% CI 0.011–0.135) were less likely to practice self‐medication, while people with primary education (AOR = 3.00, 95% CI 1.217, 7.435), income less than 3,000 birr (AOR = 5.46, 95% CI 1.41, 21.1), participants in the first (AOR = 4.183, 95% CI 2.12, 8.24) and second trimesters (AOR = 2.05, 95% CI 1.18, 3.56), pregnant women who lived in rural areas (AOR = 1.579, 95% CI 1.103–2.260), and people who previously practiced self‐medication (AOR = 8.2, 95% CI 5.04, 13.3) were more likely to practice self‐medication. Conclusion. From the present finding, it can be concluded that self‐medication among pregnant women is high. Previous self‐medication practice, gestation period, educational status, monthly income, no preconception care, no health insurance, being a housewife, farmer, and place of residence were significantly associated with self‐medication practice. Therefore, preventive measures such as proper counseling during dispensing, awareness creation programs on preconception care, and enrolling in health insurance programs to minimize the practice of self‐medication are necessary.
Applications of Subordination for Holomorphic Functions Stated by Generalized By‐Product Operator
Authors: Hameed Mustafa I. , Al-Dulaimi Shaheed Jameel , Joshua Hussaini , Hameed Ismael I. , Ibrahim Israa A. , Oshinubi Kayode
Published: August 2024

The aim of this research is to investigate certain problems of differential subordination and superordination of analytic univalent functions in an open unit disk. Furthermore, the universal by‐product operator and geometric properties such as coefficient inequalities are investigated. Remarkable results on the differential subordination and superordination of analytic univalent functions and results using higher derivative operator for differential subordination are obtained. Some interesting applications of subordination in the unit disk are obtained using convolution and convexity.
Supplementary Methods from Medical Care Costs Associated with Cancer Survivorship in the United States
Authors: Mariotto Angela B. , Enewold Lindsey , Zhao Jingxuan , Zeruto Christopher A. , Yabroff K. Robin
Published: August 2024

Methods to estimate and project prevalence
Supplemental Table 3 from Personalized ctDNA for Monitoring Disease Status in Head and Neck Squamous Cell Carcinoma
Authors: Hanna Glenn J. , Dennis Michael J. , Scarfo Nicole , Mullin Michelle S. , Sethi Rosh K.V. , Sehgal Kartik , Annino Donald J. , Goguen Laura A. , Haddad Robert I. , Tishler Roy B. , Margalit Danielle N. , Uppaluri Ravindra , Schoenfeld Jonathan D. , Rettig Eleni M.
Published: August 2024

Supplemental Table 3. Clinical and pathologic characteristics based on ctDNA follow-up testing availability.
Supplemental Figure 2 from Personalized ctDNA for Monitoring Disease Status in Head and Neck Squamous Cell Carcinoma
Authors: Hanna Glenn J. , Dennis Michael J. , Scarfo Nicole , Mullin Michelle S. , Sethi Rosh K.V. , Sehgal Kartik , Annino Donald J. , Goguen Laura A. , Haddad Robert I. , Tishler Roy B. , Margalit Danielle N. , Uppaluri Ravindra , Schoenfeld Jonathan D. , Rettig Eleni M.
Published: August 2024

Supplemental Figure 2. Survival curves.
Supplementary Video S2 from Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity
Authors: Chen Hsuan-An , Ho Yu-Jui , Mezzadra Riccardo , Adrover Jose M. , Smolkin Ryan , Zhu Changyu , Woess Katharina , Bernstein Nicholas , Schmitt Georgia , Fong Linda , Luan Wei , Wuest Alexandra , Tian Sha , Li Xiang , Broderick Caroline , Hendrickson Ronald C. , Egeblad Mikala , Chen Zhenghao , Alonso-Curbelo Direna , Lowe Scott W.
Published: August 2024

Supplementary Video S2 from Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity
Supplementary Video S1 from Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity
Authors: Chen Hsuan-An , Ho Yu-Jui , Mezzadra Riccardo , Adrover Jose M. , Smolkin Ryan , Zhu Changyu , Woess Katharina , Bernstein Nicholas , Schmitt Georgia , Fong Linda , Luan Wei , Wuest Alexandra , Tian Sha , Li Xiang , Broderick Caroline , Hendrickson Ronald C. , Egeblad Mikala , Chen Zhenghao , Alonso-Curbelo Direna , Lowe Scott W.
Published: August 2024

Supplementary Video S1 from Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity
Supplementary Figure S1-S16 from Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity
Authors: Chen Hsuan-An , Ho Yu-Jui , Mezzadra Riccardo , Adrover Jose M. , Smolkin Ryan , Zhu Changyu , Woess Katharina , Bernstein Nicholas , Schmitt Georgia , Fong Linda , Luan Wei , Wuest Alexandra , Tian Sha , Li Xiang , Broderick Caroline , Hendrickson Ronald C. , Egeblad Mikala , Chen Zhenghao , Alonso-Curbelo Direna , Lowe Scott W.
Published: August 2024

Supplementary figures complement main figures to show that senescent cells have a rewired environmental signal sensing phenotype, exemplified by an enhanced IFN-g signaling, to facilitate anti-tumor immunity.
Figure 6 from Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity
Authors: Chen Hsuan-An , Ho Yu-Jui , Mezzadra Riccardo , Adrover Jose M. , Smolkin Ryan , Zhu Changyu , Woess Katharina , Bernstein Nicholas , Schmitt Georgia , Fong Linda , Luan Wei , Wuest Alexandra , Tian Sha , Li Xiang , Broderick Caroline , Hendrickson Ronald C. , Egeblad Mikala , Chen Zhenghao , Alonso-Curbelo Direna , Lowe Scott W.
Published: August 2024

Senescence enhances IFNγ-mediated heterotypic signaling from activated immune cells to tumor cells. A, Graphic illustration of the IGS reporter. (Created with BioRender.com.) B, Left, representative flow cytometry plots measuring ZsGreen1 signals in proliferating and senescent NSP cells treated with 1 ng/mL IFNγ. Right, quantification of the percentage of ZsGreen1-positive cells upon IFNγ treatment. MFI, median fluorescence intensity. C and D, Representative 3D imaging of tissue-cleared tumors from the orthotopically injected liver NSP cell line expressing IGS reporter (C). Quantification of 3 randomly selected fields from the liver tumor of each mouse (D). n = 5 and n = 3 for the proliferating and senescent groups (9 days after p53 restoration), respectively. Scale bars, 100 μm. E, Top, cytometric bead array assay for the IFNγ level from in vivo tumor tissue lysate samples (7 days after p53 restoration). Bottom, transcripts of indicated genes from RNA-seq of in vivo bulk samples of tumors generated by HTVI (PRO, p53 off; SEN, p53 restoration for 12 days). TPM, transcripts per kilobase million. Noted Ifna/b cluster contains 14 Ifna subtypes and 1 Ifnb gene. F and G, Expression of Ifng in tumor-infiltrating immune cells profiled by scRNA-seq in the NSP transplantable model (as in Fig. 2, sample collected at day 8 after p53 restoration). H, Uniform manifold approximation and projection plot of the expression of Havcr2 (encoding TIM3) and Ifng in CD8 T cells harvested from proliferating (P) and senescent (S) tumor lesion. Top panel is replicated from Fig. 2F (left) to indicate cells corresponding to each condition. I, Quantification of ZsGreen1 intensity of NSP tumor cells in the OT-I T-cell and SIINFEKL-expressing tumor cell coculture experiment (effector-to-target ratio, 5:1) after 20 hours of coculture. Signal measured by flow cytometry. T + P, trametinib plus palbociclib. See experimental details in Supplementary Fig. S12E. Data are presented as mean ± SEM. Two-tailed Student t test was used. *, P < 0.05; **, P < 0.01; ***, P < 0.001.
Figure 5 from Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity
Authors: Chen Hsuan-An , Ho Yu-Jui , Mezzadra Riccardo , Adrover Jose M. , Smolkin Ryan , Zhu Changyu , Woess Katharina , Bernstein Nicholas , Schmitt Georgia , Fong Linda , Luan Wei , Wuest Alexandra , Tian Sha , Li Xiang , Broderick Caroline , Hendrickson Ronald C. , Egeblad Mikala , Chen Zhenghao , Alonso-Curbelo Direna , Lowe Scott W.
Published: August 2024

Senescence and EC IFNγ cooperate to upregulate antigen processing and presentation machinery. A and B, mRNA expression of genes in proliferating and senescent NSP cells in vitro in the presence or absence of IFNγ (50 pg/mL) treatment. mRNA level is normalized to the mean expression of the gene in all samples. A, DEG-encoding SASP factors in our model. B, IFNγ response genes from the Hallmark signature database. C, RT-qPCR of selected antigen presentation pathway genes in proliferating and senescent cells treated with low (50 pg/mL) or high (1 ng/mL) concentration of IFNγ. Samples are from 2 biological replicates. D, MHC-I level of proliferating and senescent cells treated with IFNγ for 24 hours measured by flow cytometry. MFI, median fluorescence intensity. Data are presented as mean ± SEM.
Figure 4 from Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity
Authors: Chen Hsuan-An , Ho Yu-Jui , Mezzadra Riccardo , Adrover Jose M. , Smolkin Ryan , Zhu Changyu , Woess Katharina , Bernstein Nicholas , Schmitt Georgia , Fong Linda , Luan Wei , Wuest Alexandra , Tian Sha , Li Xiang , Broderick Caroline , Hendrickson Ronald C. , Egeblad Mikala , Chen Zhenghao , Alonso-Curbelo Direna , Lowe Scott W.
Published: August 2024

Senescent cells are primed to sense and amplify IFNγ signaling. A and B, IFNGR1 level on proliferating and senescent cells profiled by mass spectrometry (A) and validated by flow cytometry (B). AU, arbitrary unit. Data are presented as mean ± SEM. n = 6 for both the proliferating and senescent groups. C, Transcriptomic analysis of selected genes regulating IFNγ signaling from RNA-seq data of 3 independent p53-restorable cell lines (NSP, NSM2, and NSP5) restoring p53 along with NSP cells treated with two other senescence triggers. SEN/PRO, senescent/proliferating; T + P, trametinib plus palbociclib. D, mRNA expression of selected genes involved in IFNγ signaling in human cell lines triggered to senesce. Treatment: Ali, alisertib; Eto, etoposide; number indicates the length of treatment (days). Data are obtained from the public dataset SENESCopedia (44). E, Top, immunoblot analysis of NSP cells under different senescent triggers in the presence or absence of IFNγ (1 ng/mL). Bottom, quantification of the intensity of signal from immunoblot. p-STAT1, phospho-STAT1 (Tyr701).
Figure 3 from Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity
Authors: Chen Hsuan-An , Ho Yu-Jui , Mezzadra Riccardo , Adrover Jose M. , Smolkin Ryan , Zhu Changyu , Woess Katharina , Bernstein Nicholas , Schmitt Georgia , Fong Linda , Luan Wei , Wuest Alexandra , Tian Sha , Li Xiang , Broderick Caroline , Hendrickson Ronald C. , Egeblad Mikala , Chen Zhenghao , Alonso-Curbelo Direna , Lowe Scott W.
Published: August 2024

Senescence remodels tissue-sensing programs and cell-surfaceome landscape. A, Gene set enrichment analysis (Reactome) of RNA-seq data from proliferating (PRO, p53 off) versus senescent (SEN, p53 on for 8 days) NSP liver tumor cells in vitro. NES, normalized enrichment score. B, Subcellular localization of DEGs (P < 0.05; fold change > 2) in all detected genes [transcripts per kilobase million (TPM) > 1] from RNA-seq. C, Gene ontology (GO) analysis of DEGs encoding PM proteins upregulated in senescent cells. TM, transmembrane. D, Transcriptomic analysis of all DEGs (proliferating vs. senescent) in the presence or absence of JQ1 treatment. The C1 cluster (in red) contains the senescence-specific genes sensitive to JQ1, and the C4 cluster (in blue) contains the proliferation-specific genes sensitive to JQ1. E, Meta-analysis of RNA-seq dataset from SENESCopedia by performing subcellular localization of DEGs (same as Fig. 2D) and Fisher exact test to examine the relative enrichment of upregulated and downregulated EC/PM-DEGs deviated from the random distribution. See also Supplementary Fig. S7E and S7F. F, Mass spectrometry (MS) analysis of PM-enriched proteome in proliferating and senescent cells. Protein level is normalized to mean expression of the protein of all samples. Controls are the samples without biotin labeling serving as background. Red and blue boxes represent proteins enriched in senescent and proliferating cells, respectively. n = 6 for both the senescent and proliferating experimental groups, and n = 3 and 4, respectively, for their control. G, Distribution of upregulated and downregulated GeneCards-annotated PM proteins profiled by MS. NC, no change. H, Volcano plot of GeneCards-annotated PM proteins profiled by MS.
Data from Senescence Rewires Microenvironment Sensing to Facilitate Antitumor Immunity
Authors: Chen Hsuan-An , Ho Yu-Jui , Mezzadra Riccardo , Adrover Jose M. , Smolkin Ryan , Zhu Changyu , Woess Katharina , Bernstein Nicholas , Schmitt Georgia , Fong Linda , Luan Wei , Wuest Alexandra , Tian Sha , Li Xiang , Broderick Caroline , Hendrickson Ronald C. , Egeblad Mikala , Chen Zhenghao , Alonso-Curbelo Direna , Lowe Scott W.
Published: August 2024

Abstract
Cellular senescence involves a stable cell-cycle arrest coupled to a secretory program that, in some instances, stimulates the immune clearance of senescent cells. Using an immune-competent liver cancer model in which senescence triggers CD8 T cell–mediated tumor rejection, we show that senescence also remodels the cell-surface proteome to alter how tumor cells sense environmental factors, as exemplified by type II interferon (IFNγ). Compared with proliferating cells, senescent cells upregulate the IFNγ receptor, become hypersensitized to microenvironmental IFNγ, and more robustly induce the antigen-presenting machinery—effects also recapitulated in human tumor cells undergoing therapy-induced senescence. Disruption of IFNγ sensing in senescent cells blunts their immune-mediated clearance without disabling the senescence state or its characteristic secretory program. Our results demonstrate that senescent cells have an enhanced ability to both send and receive environmental signals and imply that each process is required for their effective immune surveillance.
Significance:
Our work uncovers an interplay between tissue remodeling and tissue-sensing programs that can be engaged by senescence in advanced cancers to render tumor cells more visible to the adaptive immune system. This new facet of senescence establishes reciprocal heterotypic signaling interactions that can be induced therapeutically to enhance antitumor immunity.

See the interview with Direna Alonso-Curbelo, PhD, recipient of the inaugural Cancer Discovery Early Career Award: https://vimeo.com/992987447

See related article by Marin et al., p. 410.

This article is highlighted in the In This Issue feature, p. 247
Disparate Pathways for Extrachromosomal DNA Biogenesis and Genomic DNA Repair
Authors: Rose John C. , Belk Julia A. , Wong Ivy Tsz-Lo , Luebeck Jens , Horn Hudson T. , Daniel Bence , Jones Matthew G. , Yost Kathryn E. , Hung King L. , Kolahi Kevin S. , Curtis Ellis J. , Kuo Calvin J. , Bafna Vineet , Mischel Paul S. , Chang Howard Y.
Published: August 2024

Oncogene amplification on extrachromosomal DNA (ecDNA) is a pervasive driver event in cancer, yet our understanding of how ecDNA forms is limited. In this study, we couple a CRISPR-based method for ecDNA induction with extensive characterization of newly formed ecDNAs to examine their biogenesis. We find that DNA circularization is efficient, irrespective of 3D genome context, with the formation of 800 kb, 1 Mb, and 1.8 Mb ecDNAs reaching or exceeding 15%. We show nonhomologous end joining and microhomology-mediated end joining both contribute to ecDNA formation, whereas inhibition of DNA-PK catalytic subunit and ATM have opposing impacts on ecDNA formation. ecDNA and the corresponding chromosomal excision scar can form at significantly different rates and respond differently to DNA-PK catalytic subunit and ATM inhibition. Taken together, our results support a model of ecDNA formation in which double-strand break ends dissociate from their legitimate ligation partners prior to joining of illegitimate ends to form the ecDNA and excision scar.

Significance:

Our study harnesses a CRISPR-based method to examine ecDNA biogenesis, uncovering efficient circularization between double-strand breaks. ecDNAs and their corresponding chromosomal scars can form via nonhomologous end joining or microhomology-mediated end joining, but the ecDNA and scar formation processes are distinct. Based on our findings, we establish a mechanistic model of excisional ecDNA formation.
Supplementary Table 2 from Molecular Pathways and Cellular Subsets Associated with Adverse Clinical Outcomes in Overlapping Immune-Related Myocarditis and Myositis
Authors: Siddiqui Bilal A. , Palaskas Nicolas L. , Basu Sreyashi , Dai Yibo , He Zhong , Yadav Shalini S. , Allison James P. , Sheth Rahul A. , Tummala Sudhakar , Buja Maximilian , Bhattacharjee Meenakshi B. , Iliescu Cezar , Rawther-Karedath Anishia , Deswal Anita , Wang Linghua , Sharma Padmanee , Subudhi Sumit K.
Published: August 2024

Clinical characteristics of individual patients with immune-related myocarditis and/or myositis
Supplementary Figure 7 from Molecular Pathways and Cellular Subsets Associated with Adverse Clinical Outcomes in Overlapping Immune-Related Myocarditis and Myositis
Authors: Siddiqui Bilal A. , Palaskas Nicolas L. , Basu Sreyashi , Dai Yibo , He Zhong , Yadav Shalini S. , Allison James P. , Sheth Rahul A. , Tummala Sudhakar , Buja Maximilian , Bhattacharjee Meenakshi B. , Iliescu Cezar , Rawther-Karedath Anishia , Deswal Anita , Wang Linghua , Sharma Padmanee , Subudhi Sumit K.
Published: August 2024

Differentially expressed genes (DEGs) in Cytotoxic CD8+ T Cells
Supplementary Figure 5 from Molecular Pathways and Cellular Subsets Associated with Adverse Clinical Outcomes in Overlapping Immune-Related Myocarditis and Myositis
Authors: Siddiqui Bilal A. , Palaskas Nicolas L. , Basu Sreyashi , Dai Yibo , He Zhong , Yadav Shalini S. , Allison James P. , Sheth Rahul A. , Tummala Sudhakar , Buja Maximilian , Bhattacharjee Meenakshi B. , Iliescu Cezar , Rawther-Karedath Anishia , Deswal Anita , Wang Linghua , Sharma Padmanee , Subudhi Sumit K.
Published: August 2024

Hierarchical clustering based on Euclidean distance of expression in CD45- cells
Supplementary Figure 4 from Molecular Pathways and Cellular Subsets Associated with Adverse Clinical Outcomes in Overlapping Immune-Related Myocarditis and Myositis
Authors: Siddiqui Bilal A. , Palaskas Nicolas L. , Basu Sreyashi , Dai Yibo , He Zhong , Yadav Shalini S. , Allison James P. , Sheth Rahul A. , Tummala Sudhakar , Buja Maximilian , Bhattacharjee Meenakshi B. , Iliescu Cezar , Rawther-Karedath Anishia , Deswal Anita , Wang Linghua , Sharma Padmanee , Subudhi Sumit K.
Published: August 2024

Analysis of CD45- subpopulations in cardiac muscle
Supplementary Figure 2 from Molecular Pathways and Cellular Subsets Associated with Adverse Clinical Outcomes in Overlapping Immune-Related Myocarditis and Myositis
Authors: Siddiqui Bilal A. , Palaskas Nicolas L. , Basu Sreyashi , Dai Yibo , He Zhong , Yadav Shalini S. , Allison James P. , Sheth Rahul A. , Tummala Sudhakar , Buja Maximilian , Bhattacharjee Meenakshi B. , Iliescu Cezar , Rawther-Karedath Anishia , Deswal Anita , Wang Linghua , Sharma Padmanee , Subudhi Sumit K.
Published: August 2024

Landscape of CD45- (non-immune) populations from patient cardiac and skeletal muscle tissues
Supplementary Figure 18 from Molecular Pathways and Cellular Subsets Associated with Adverse Clinical Outcomes in Overlapping Immune-Related Myocarditis and Myositis
Authors: Siddiqui Bilal A. , Palaskas Nicolas L. , Basu Sreyashi , Dai Yibo , He Zhong , Yadav Shalini S. , Allison James P. , Sheth Rahul A. , Tummala Sudhakar , Buja Maximilian , Bhattacharjee Meenakshi B. , Iliescu Cezar , Rawther-Karedath Anishia , Deswal Anita , Wang Linghua , Sharma Padmanee , Subudhi Sumit K.
Published: August 2024

Comparison of the transcriptional programs between samples from patients with myasthenia gravis (MG) versus patients without MG
Supplementary Figure 17 from Molecular Pathways and Cellular Subsets Associated with Adverse Clinical Outcomes in Overlapping Immune-Related Myocarditis and Myositis
Authors: Siddiqui Bilal A. , Palaskas Nicolas L. , Basu Sreyashi , Dai Yibo , He Zhong , Yadav Shalini S. , Allison James P. , Sheth Rahul A. , Tummala Sudhakar , Buja Maximilian , Bhattacharjee Meenakshi B. , Iliescu Cezar , Rawther-Karedath Anishia , Deswal Anita , Wang Linghua , Sharma Padmanee , Subudhi Sumit K.
Published: August 2024

Cell-cell communication analysis from endothelial cells and myeloid cells to cytotoxic T cells in myositis
Supplementary Figure 13 from Molecular Pathways and Cellular Subsets Associated with Adverse Clinical Outcomes in Overlapping Immune-Related Myocarditis and Myositis
Authors: Siddiqui Bilal A. , Palaskas Nicolas L. , Basu Sreyashi , Dai Yibo , He Zhong , Yadav Shalini S. , Allison James P. , Sheth Rahul A. , Tummala Sudhakar , Buja Maximilian , Bhattacharjee Meenakshi B. , Iliescu Cezar , Rawther-Karedath Anishia , Deswal Anita , Wang Linghua , Sharma Padmanee , Subudhi Sumit K.
Published: August 2024

Cell-cell communication analysis from myeloid cells and cytotoxic T cells to endothelial cells in myocarditis
Supplementary Figure 11 from Molecular Pathways and Cellular Subsets Associated with Adverse Clinical Outcomes in Overlapping Immune-Related Myocarditis and Myositis
Authors: Siddiqui Bilal A. , Palaskas Nicolas L. , Basu Sreyashi , Dai Yibo , He Zhong , Yadav Shalini S. , Allison James P. , Sheth Rahul A. , Tummala Sudhakar , Buja Maximilian , Bhattacharjee Meenakshi B. , Iliescu Cezar , Rawther-Karedath Anishia , Deswal Anita , Wang Linghua , Sharma Padmanee , Subudhi Sumit K.
Published: August 2024

Complement activation associated with serum autoantibodies and tissue IgG deposition in ICT-induced myocarditis and myositis
Supplementary Figure 10 from Molecular Pathways and Cellular Subsets Associated with Adverse Clinical Outcomes in Overlapping Immune-Related Myocarditis and Myositis
Authors: Siddiqui Bilal A. , Palaskas Nicolas L. , Basu Sreyashi , Dai Yibo , He Zhong , Yadav Shalini S. , Allison James P. , Sheth Rahul A. , Tummala Sudhakar , Buja Maximilian , Bhattacharjee Meenakshi B. , Iliescu Cezar , Rawther-Karedath Anishia , Deswal Anita , Wang Linghua , Sharma Padmanee , Subudhi Sumit K.
Published: August 2024

Comparison of myeloid cell subclusters in skeletal muscle with previously reported subsets
Figure S2 from FLT3/CD99 Bispecific Antibody–Based Nanoparticles for Acute Myeloid Leukemia
Authors: Ali Atham , Phan Alvin , Vaikari Vijaya , Park Mincheol , Pospiech Mateusz , Chu Ryan , Meng Yiting , MacKay John A. , Alachkar Houda
Published: August 2024

Figure S2 – FLT3 and CD99 surface level expression in primary blasts of sample USC001 and USC100.
Figure S1 from FLT3/CD99 Bispecific Antibody–Based Nanoparticles for Acute Myeloid Leukemia
Authors: Ali Atham , Phan Alvin , Vaikari Vijaya , Park Mincheol , Pospiech Mateusz , Chu Ryan , Meng Yiting , MacKay John A. , Alachkar Houda
Published: August 2024

Figure S1 – Flow Panels of Annexin and PI staining of U937 Cells following treatment with FLT3-A192, CD99-A192 and Co-Assembled CD99-A192 and FLT3-A192.