bluuebunny/crossref_metadata_2025 huggingface dataset:
Breadth and polyfunctionality of T cell responses to human cytomegalovirus in men who have sex with men: relationship with HIV infection and frailty
Authors: Zhang Weiying , Nilles Tricia L. , Bream Jay H. , Li Huifen , Malash Eslam , Langan Susan , Leng Sean X. , Margolick Joseph B.
Published: September 2024

Cytomegalovirus (CMV)-seropositive adults have large T cell responses to a wide range of CMV proteins; these responses have been associated with chronic inflammation and frailty in people with or without HIV infection. We analyzed the relationships between chronic HIV infection, frailty, and the breadth and polyfunctionality of CD4 and CD8 T cell responses to CMV. Peripheral blood mononuclear cells from 42 men (20 without HIV and 22 with virologically suppressed HIV) in the Multicenter AIDS Cohort Study (MACS) were stimulated with peptide pools spanning 19 CMV open reading frames (ORFs). As measured by flow cytometry and intracellular cytokine staining for IFN-γ, TNF-α, and IL-2, CD8 T cells from men with HIV responded to significantly more CMV ORFs than those from men without HIV. This was primarily due to a broader response to ORFs that are expressed during the late phase of CMV replication. The number of ORFs to which a participant’s T cells responded was positively correlated with the sum of all that individual’s T cell responses; these correlations were weaker in men with than without HIV. Polyfunctional CMV-specific CD4 responses (production of more than one cytokine) were significantly lower in men with than without HIV. Frailty status did not substantially affect the breadth or magnitude of the CMV-specific T cell responses. These results suggest that immune control of CMV infection is affected more by chronic HIV infection than by frailty. The differences between men with and without HIV were similar to those reported between young and older adults without HIV.

IMPORTANCE

T cell responses to chronic cytomegalovirus (CMV) infection have significant biological and clinical implications in HIV infection and aging. Here, we systematically analyzed the breadth, magnitude, and polyfunctionality of T cell responses to multiple CMV antigens in men with and without HIV in the Multicenter AIDS Cohort Study (MACS), a longstanding study of the natural and treated history of HIV-1 infection in men who have sex with men. We found that the breadth and polyfunctionality of T cell responses to CMV were different between men with chronic, treated HIV and those without HIV. The reason for these differences is unknown, but these findings suggest that people with treated HIV may have more frequent CMV reactivation than people without HIV. Differences between people with and without HIV also resembled differences reported between young and older adults without HIV, supporting a role for the immune responses to CMV in the aging process.
Annotation-free prediction of microbial dioxygen utilization
Authors: Flamholz Avi I. , Goldford Joshua E. , Richter Philippa A. , Larsson Elin M. , Jinich Adrian , Fischer Woodward W. , Newman Dianne K.
Published: September 2024

Aerobes require dioxygen (O
2
) to grow; anaerobes do not. However, nearly all microbes—aerobes, anaerobes, and facultative organisms alike—express enzymes whose substrates include O
2
, if only for detoxification. This presents a challenge when trying to assess which organisms are aerobic from genomic data alone. This challenge can be overcome by noting that O
2
utilization has wide-ranging effects on microbes: aerobes typically have larger genomes encoding distinctive O
2
-utilizing enzymes, for example. These effects permit high-quality prediction of O
2
utilization from annotated genome sequences, with several models displaying ≈80% accuracy on a ternary classification task for which blind guessing is only 33% accurate. Since genome annotation is compute-intensive and relies on many assumptions, we asked if annotation-free methods also perform well. We discovered that simple and efficient models based entirely on genomic sequence content—e.g., triplets of amino acids—perform as well as intensive annotation-based classifiers, enabling rapid processing of genomes. We further show that amino acid trimers are useful because they encode information about protein composition and phylogeny. To showcase the utility of rapid prediction, we estimated the prevalence of aerobes and anaerobes in diverse natural environments cataloged in the Earth Microbiome Project. Focusing on a well-studied O
2
gradient in the Black Sea, we found quantitative correspondence between local chemistry (O
2
:sulfide concentration ratio) and the composition of microbial communities. We, therefore, suggest that statistical methods like ours might be used to estimate, or “sense,” pivotal features of the chemical environment using DNA sequencing data.

IMPORTANCE

We now have access to sequence data from a wide variety of natural environments. These data document a bewildering diversity of microbes, many known only from their genomes. Physiology—an organism’s capacity to engage metabolically with its environment—may provide a more useful lens than taxonomy for understanding microbial communities. As an example of this broader principle, we developed algorithms that accurately predict microbial dioxygen utilization directly from genome sequences without annotating genes, e.g., by considering only the amino acids in protein sequences. Annotation-free algorithms enable rapid characterization of natural samples, highlighting quantitative correspondence between sequences and local O
2
levels in a data set from the Black Sea. This example suggests that DNA sequencing might be repurposed as a multi-pronged chemical sensor, estimating concentrations of O
2
and other key facets of complex natural settings.
Research priorities for progressive pulmonary fibrosis in the UK
Authors: Fabbri Laura , Russell Anne-Marie , Chaudhuri Nazia , Adams Wendy , Cowan Katherine , Conway John , Dickinson Wendy , Gibbons Michael , Hart Simon , Jones Steve , Lynch-Wilson Jenny , McMillan Tom , Milward Steve , Ward Maureen , Wright Louise Elisabeth , Jenkins Gisli
Published: September 2024

Introduction

Health research bodies recommend patient involvement and engagement in research and healthcare planning, although their implementation is not yet widespread. This deficiency extends to progressive pulmonary fibrosis (PPF), where crucial aspects remain unknown, including causal mechanisms, curative treatments and optimal symptom management. This study addresses these gaps by seeking stakeholders’ perspectives to guide research and treatment directions.

Method

A priority-setting partnership was established to explore stakeholders’ priorities in the diagnosis, treatment, management and care of PPF, including idiopathic pulmonary fibrosis which is the archetypal PPF. Stakeholders included people living with PPF, their carers, relatives and healthcare professionals involved in their management.

Results

Through an online open-ended survey, 2542 responses were collected from 638 stakeholders. Thematic analysis identified 48 specific research questions, which were then cross-referenced with academic literature to pinpoint research gaps. Following the evidence check, 44 unanswered questions were shortlisted by 834 stakeholders in a second online survey. Ultimately, a top 10 priority list was established through consensus.

The prioritised research questions include (1) improved diagnosis accuracy and timing, (2) development of new treatments, (3) enhanced accuracy in primary care, (4) optimal timing for drug and non-drug interventions, (5) effective cough treatment, (6) early intervention for PPF, (7) improved survival rates, (8) symptom reduction, (9) impact of interventions on life expectancy and (10) new treatments with reduced side effects.

Conclusion

Stakeholders’ priorities can be summarised into five areas: early diagnosis, drug and non-drug treatments, survival and symptom management. Ideally, these topics should guide funding bodies and health policies.
Comparison of established and preliminarily proposed ASAS MRI working group cut-offs for inflammatory MRI lesions in the sacroiliac joints in radiographic and non-radiographic axial spondyloarthritis
Authors: Baraliakos Xenofon , Machado Pedro M , Bauer Lars , Hoepken Bengt , Kim Mindy , Kumke Thomas , Tham Rachel , Rudwaleit Martin
Published: September 2024

Background

A consensus definition for active sacroiliitis by MRI, mentioned in the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axial spondyloarthritis (axSpA), was published in 2009 and included a qualitative and quantitative MRI cut-off component. In 2021, updates to the quantitative component were preliminarily proposed. This post hoc analysis of part A of the phase 3 open-label C-OPTIMISE study (NCT02505542) explores the differences by applying the 2009 and preliminary 2021 inflammatory cut-offs on clinical outcomes of axSpA patients treated with certolizumab pegol.

Methods

Baseline MRI scans were used to classify 657 patients as MRI+ or MRI– according to the quantitative components of the 2009 and preliminary 2021 MRI cut-offs for inflammatory lesions. Clinical outcomes, including ASAS ≥40% improvement (ASAS40), Ankylosing Spondylitis Disease Activity Score and Bath Ankylosing Spondylitis Disease Activity Index, were reported to week 48.

Results

Across all analysed outcomes, 2009 MRI+ and preliminary 2021 MRI+ subgroups showed similar results. Notably, clinical outcomes for the discordant group (2009 MRI+but preliminary 2021 MRI– group; 53/657 [8.1%]) were close to those seen in MRI– patients according to either 2009 or preliminary 2021 inflammatory cut-offs, and notably different from the totality of MRI+ subgroups.

Conclusion

This analysis suggests that the preliminary 2021 cut-offs for MRI inflammatory lesions may slightly increase the specificity of the quantitative part of the 2009 MRI inflammatory lesion definition. The effects of the updated MRI cut-offs need to be assessed on the basis of efficacy outcomes and with the inclusion of aspects of structural changes.

Trial registration number

NCT02505542.
Early Miocene larger foraminifera from Suwadi Island, northern Oman
Authors: Afzal Jawad , Racey Andrew
Published: September 2024

Suwadi Island is located off the coast of northern Oman on top of an uplifted horst block that exposes a sequence of the Early Miocene Sur Formation. These shallow-marine carbonates and calcareous clastics are unconformably overlain by continental deposits of the Middle Miocene–Pliocene Barzaman Formation. The Sur Formation microfauna is dominated by the larger foraminifera
Miogypsina
,
Pseudotaberina
and
Palaeonummulites
with rarer occurrences of
Operculina
,
Borelis
,
Dendritina
,
Peneroplis
,
Archaias
and
Lepidocyclina
(
Nephrolepidina
), which indicates an early Tf1 Letter Stage that is equivalent to the Shallow Benthic Zone SBZ 25 (early Burdigalian age). Microfacies and palaeoecological analysis indicate depositional environments ranging from tidal flats to proximal middle ramp with shoal development near fair-weather wave base. Similar sediments and microfaunas are observed further ‘offshore’ to the north on the Daymaniyat islands. Oman is located at the boundary between the Mediterranean and the Indo–West Pacific faunal provinces, and the described microfauna provides valuable biogeographic data on the ‘connectivity’ of these two bioprovinces during the Burdigalian.
ZIP-CNN: Design Space Exploration for CNN Implementation within a MCU
Authors: Garbay Thomas , Hachicha Khalil , Dobias Petr , Pinna Andrea , Hocine Karim , Dron Wilfried , Lusich Pedro , Khalis Imane , Granado Bertrand
Published: September 2024

Embedded systems based on Microcontroller Units (MCUs) often gather significant quantities of data and solve various issues. Convolutional Neural Networks (CNNs) have proven their effectiveness in solving computer vision and natural language processing tasks. However, implementing CNNs within MCUs is challenging due to their high inference costs, which varies widely depending on hardware targets and CNN topologies. Despite state-of-the-art advancements, no efficient design space exploration solutions handle the wide variety of implementation solutions. In this article, we introduce the ZIP-CNN design space exploration methodology, which facilitates CNN implementation within MCUs. We developed a model that quantitatively estimates the latency, energy consumption, and memory space required to run a CNN within an MCU. This model accounts for algorithmic reductions such as knowledge distillation, pruning, or quantization and applies to any CNN topology. To demonstrate the efficiency of our methodology, we investigated LeNet5, ResNet8, and ResNet26 within three different MCUs. We made materials and supplementary results available in a GitHub repository:
https://github.com/ThGbay/ZIP-CNN
. The proposed method was empirically verified on three hardware targets running at 14 different operating frequencies. The three CNN topologies investigated were implemented in their default configuration in FP32, and also reduced with INT8 quantization, pruning at five different rates and with knowledge distillation. The estimates of our model are very reliable with an error of 3.29% to 15.23% for latency, 3.12% to 10.34% for energy consumption, and 1.95% to 6.31% for memory space. These results are based on on-device measurements.
A Large-Scale Study of IoT Security Weaknesses and Vulnerabilities in the Wild
Authors: Selvaraj Madhu , Uddin Gias
Published: September 2024

Internet of Things (IoT) is defined as the connection between places and physical objects (i.e., things) over the internet/network via smart computing devices. IoT is a rapidly emerging paradigm that now encompasses almost every aspect of our modern life. As these devices differ from traditional computing, it is important to understand the challenges IoT developers face while implementing proper security measures in their IoT devices. We observed that IoT software developers share solutions to programming questions as code examples on three Stack Exchange Q & A sites: Stack Overflow (SO), Arduino, and Raspberry Pi. Previous research studies found vulnerabilities/weaknesses in C/C++ code examples shared in SO. However, the studies did not investigate C/C++ code examples related to IoT. The studies investigated SO code examples only. In this article, we conduct a large-scale empirical study of all IoT C/C++ code examples shared in the three Stack Exchange sites, i.e., SO, Arduino, and Raspberry Pi. From the 11,329 obtained code snippets from the three sites, we identify 29 distinct Common Weakness Enumeration (CWE) types in 609 snippets. These CWE types can be categorized into eight general weakness categories, and we observe that evaluation, memory, and initialization-related weaknesses are the most common to be introduced by users when posting programming solutions. Furthermore, we find that 39.58% of the vulnerable code snippets contain instances of CWE types that can be mapped to real-world occurrences of those CWE types (i.e., CVE instances). The most number vulnerable IoT code examples was found in Arduino, followed by SO, and Raspberry Pi. Memory type vulnerabilities are on the rise in the sites. For example, from the 3,595 mapped CVE instances, we find that 28.99% result in Denial of Service (DoS) errors, which is particularly harmful for network reliant IoT devices such as smart cars. Our study results can guide various IoT stakeholders to be aware of such vulnerable IoT code examples and to inform IoT researchers during their development of tools that can help prevent developers the sharing of such vulnerable code examples in the sites.
Reframing Adolescent Identity: A Global Perspective for the Digital Age
Authors: Sirin Selcuk R. , Brauer Scott Z. , Tugberk R. Canan
Published: September 2024

This review provides a comprehensive evaluation of adolescent identity development research, critically examining the significant gap between the global distribution of adolescents and the focus of scholarly work. While over 85% of the world's youth live in the majority world—Africa, Asia, and Latin America—only 15% of developmental psychology studies explore these populations, revealing a critical gap in global perspectives on adolescent identity development. This review also emphasizes the lack of theoretical and empirical focus on the transformative role of digital technology in shaping identities. Through a systematic review of research, we provide both an empirical base and a conceptual framework to understand adolescent identity in an increasingly connected world. We also suggest several concrete steps for incorporating global perspectives and digital realities into developmental psychology research in general and identity development research in particular.
The Origins and Emergence of Self-Representation
Authors: Southgate Victoria
Published: September 2024

Although a reflective self-awareness is often considered to be the pinnacle of human consciousness, it takes time to develop, and behaviors indicating a conceptual self-representation appear only toward the end of the second year of life. How it develops has been the subject of much speculation, but little empirical data have targeted causal mechanisms. I first review early behaviors that likely do or do not indicate a reflective self-awareness. I then draw on data indicating a continuity between bodily and conceptual self-awareness, suggesting that the key to understanding how a reflective self-awareness develops is to look for its origins in a bodily self and in the earliest available signals of self-origin. Considering data from adult cognitive neuroscience, I review the mechanisms that could exploit early visceral cues and represent them as belonging to the self and the role that caregiver–infant interactions may play in this process. I conclude by considering how cross-cultural differences in the emergence of a self-concept provide important insights into the mechanisms that develop self-awareness.
Cellular, Molecular, and Genetic Mechanisms of Avian Beak Development and Evolution
Authors: Schneider Richard A.
Published: September 2024

Diverse research programs employing complementary strategies have been uncovering cellular, molecular, and genetic mechanisms essential to avian beak development and evolution. In reviewing these discoveries, I offer an interdisciplinary perspective on bird beaks that spans their derivation from jaws of dinosaurian reptiles, their anatomical and ecological diversification across major taxonomic groups, their common embryonic origins, their intrinsic patterning processes, and their structural integration. I describe how descriptive and experimental approaches, including gene expression and cell lineage analyses, tissue recombinations, surgical transplants, gain- and loss-of-function methods, geometric morphometrics, comparative genomics, and genome-wide association studies, have identified key constituent parts and putative genes regulating beak morphogenesis and evolution. I focus throughout on neural crest mesenchyme, which generates the beak skeleton and other components, and describe how these embryonic progenitor cells mediate species-specific pattern and link form and function as revealed by 20 years of research using chimeras between quail and duck embryos.
Quasinormal Modes of Bardeen Black Hole in 5‐Dimensional Gauss–Bonnet Gravity
Authors: Ge Feng-Miao , Wei Bingyuan
Published: September 2024

This study addressed the scalar field quasinormal ringing behavior of black holes. We investigated scalar field perturbations in Bardeen black hole spacetime in 5‐dimensional Einstein–Gauss–Bonnet (EGB) gravity. Using the sixth‐order Padé approximation and the finite difference method, we computed the frequency of quasinormal modes (QNMs) in the spacetime background. The calculations demonstrated that the real part of the QNMsωincreased, whereas the imaginary part decreased with increase in the magnetic charge parameterQof the Bardeen black hole for a fixed Gauss–Bonnet parameterα. This was also valid whenQwas fixed andαincreased, where in the real part of the QNMs increased and the absolute value of the imaginary part decreased. However, the change in the latter case was more significant than that in the former; thus, the frequency of eigenvibration of this black hole background under the scalar field perturbation increased and the decay of eigenvibration decreased with increase inαorQ2. Moreover, this result shows that the effect ofαon the intrinsic vibration of this black hole was greater than that ofQ.
Supplementary Data from RETRACTED: Collagen Prolyl Hydroxylases Are Essential for Breast Cancer Metastasis
Authors: Gilkes Daniele M. , Chaturvedi Pallavi , Bajpai Saumendra , Wong Carmen C. , Wei Hong , Pitcairn Stephen , Hubbi Maimon E. , Wirtz Denis , Semenza Gregg L.
Published: September 2024

Supplementary Data PDF file 764K, Supplementary Figure S1, HIF-1 dependent P4HA1 and P4HA2 induction Supplementary Figure S2, P4HA1 and P4HA2 knockdown inhibits breast cancer growth and metastasis Supplementary Figure S3, Collagen hydroxylase knockdown decreases collagen deposition in vivo Supplementary Figure S4, P4HA1 and P4HA2 knockdown inhibits growth and metastasis of MDA-MB-435 cells Supplementary Figure S5, Picrosirius red staining of mouse lungs Supplementary Figure S6, P4HA re-expression in HIF-deficient cells rescues collagen deposition and metastasis Supplementary Figure S7, DHB treatment of MDA-MB-231 Cells Supplementary Table S1, Real-time qPCR primers. Supplemental Table S2, Comparison of human P4HA1 mRNA versus mouse P4HA1 mRNA expression in tumors. Supplemental Table S3, Correlation of P4HA1 and P4HA2 mRNA expression with receptor status
Supplementary Data from ARID1A-Deficient Tumors Acquire Immunogenic Neoantigens during the Development of Resistance to Targeted Therapy
Authors: Okada Masahiro , Yamasaki Satoru , Nakazato Hiroshi , Hirahara Yuhya , Ishibashi Takuya , Kawamura Masami , Shimizu Kanako , Fujii Shin-ichiro
Published: September 2024

FigureS1-S8, TableS1-S7
Supplementary Table S4 from Multistate Gene Cluster Switches Determine the Adaptive Mitochondrial and Metabolic Landscape of Breast Cancer
Authors: Menegollo Michela , Bentham Robert B. , Henriques Tiago , Ng Seow Q. , Ren Ziyu , Esculier Clarinde , Agarwal Sia , Tong Emily T.Y. , Lo Clement , Ilangovan Sanjana , Szabadkai Zorka , Suman Matteo , Patani Neill , Ghanate Avinash , Bryson Kevin , Stein Robert C. , Yuneva Mariia , Szabadkai Gyorgy
Published: September 2024

Supplementary Table S4
Supplementary Figure S4 from Multistate Gene Cluster Switches Determine the Adaptive Mitochondrial and Metabolic Landscape of Breast Cancer
Authors: Menegollo Michela , Bentham Robert B. , Henriques Tiago , Ng Seow Q. , Ren Ziyu , Esculier Clarinde , Agarwal Sia , Tong Emily T.Y. , Lo Clement , Ilangovan Sanjana , Szabadkai Zorka , Suman Matteo , Patani Neill , Ghanate Avinash , Bryson Kevin , Stein Robert C. , Yuneva Mariia , Szabadkai Gyorgy
Published: September 2024

Supplementary Figure S4
Figure S7 from Multistate Gene Cluster Switches Determine the Adaptive Mitochondrial and Metabolic Landscape of Breast Cancer
Authors: Menegollo Michela , Bentham Robert B. , Henriques Tiago , Ng Seow Q. , Ren Ziyu , Esculier Clarinde , Agarwal Sia , Tong Emily T.Y. , Lo Clement , Ilangovan Sanjana , Szabadkai Zorka , Suman Matteo , Patani Neill , Ghanate Avinash , Bryson Kevin , Stein Robert C. , Yuneva Mariia , Szabadkai Gyorgy
Published: September 2024

Supplementary Figure S7
Figure S5 from Multistate Gene Cluster Switches Determine the Adaptive Mitochondrial and Metabolic Landscape of Breast Cancer
Authors: Menegollo Michela , Bentham Robert B. , Henriques Tiago , Ng Seow Q. , Ren Ziyu , Esculier Clarinde , Agarwal Sia , Tong Emily T.Y. , Lo Clement , Ilangovan Sanjana , Szabadkai Zorka , Suman Matteo , Patani Neill , Ghanate Avinash , Bryson Kevin , Stein Robert C. , Yuneva Mariia , Szabadkai Gyorgy
Published: September 2024

Supplementary Figure S5
Figure S2 from Multistate Gene Cluster Switches Determine the Adaptive Mitochondrial and Metabolic Landscape of Breast Cancer
Authors: Menegollo Michela , Bentham Robert B. , Henriques Tiago , Ng Seow Q. , Ren Ziyu , Esculier Clarinde , Agarwal Sia , Tong Emily T.Y. , Lo Clement , Ilangovan Sanjana , Szabadkai Zorka , Suman Matteo , Patani Neill , Ghanate Avinash , Bryson Kevin , Stein Robert C. , Yuneva Mariia , Szabadkai Gyorgy
Published: September 2024

Supplementary Figure S2
Figure 7 from Multistate Gene Cluster Switches Determine the Adaptive Mitochondrial and Metabolic Landscape of Breast Cancer
Authors: Menegollo Michela , Bentham Robert B. , Henriques Tiago , Ng Seow Q. , Ren Ziyu , Esculier Clarinde , Agarwal Sia , Tong Emily T.Y. , Lo Clement , Ilangovan Sanjana , Szabadkai Zorka , Suman Matteo , Patani Neill , Ghanate Avinash , Bryson Kevin , Stein Robert C. , Yuneva Mariia , Szabadkai Gyorgy
Published: September 2024

Pathological and clinical predictions from metabolic gene switches. A, The χ2 distribution of discrete histological features across the upper, lower, and non-fork samples of the three biclusters (MB1–MB3). Heatmap shows k-means clustering of χ2 test −log10P values, dividing the histological parameters into three groups: high, low, and no association with the bicluster. B, Visualization of histological feature distribution on the MB1 and MB2 switches. Classifiers of histological tumor type (top) and degree of nuclear pleomorphism are overlaid onto two-dimensional distribution plots of TCGA samples. The axes represent the range between the UF and LF of each bicluster. C, Clustering of histological and genetic features of samples belonging to the MB1 and MB2 switches. Fractions of samples for each feature were calculated and clustered with a custom robust to outliers distance measure function and k-means clustering. Genetic features representative of each switch position are highlighted (bold), Pam50 categories (red), and histology types and features (blue and orange, respectively). D, Key genetic and transcriptional architecture of the MB1 and MB2 switches. E–L, Survival analysis of samples in the MB1 switch. Kaplan–Meier survival plots and Cox proportional hazard analysis results from ref. 43 (E–G) and ref. 42 (H–L) are shown, generated by the kmplot.com tool (43). MB1_UF and MB1_LF bicluster (E–J) and OXPHOS (K and L) patterns (Supplementary Table S1) were used to stratify subsets of ER-positive, Her2-negative samples as indicated on the panels.
Source Data from Comprehensive Proteogenomic Profiling Reveals the Molecular Characteristics of Colorectal Cancer at Distinct Stages of Progression
Authors: Li Lingling , Jiang Dongxian , Liu Hui , Guo Chunmei , Zhang Qiao , Li Xuedong , Chen Xiaojian , Chen Zheqi , Feng Jinwen , Tan Subei , Huang Wen , Huang Jie , Xu Chen , Liu Chen-Ying , Yu Wei , Hou Yingyong , Ding Chen
Published: September 2024

Source data of the revised manuscript.
Data from E-Cadherin Induces Serine Synthesis to Support Progression and Metastasis of Breast Cancer
Authors: Lee Geonhui , Wong Claudia , Cho Anna , West Junior J. , Crawford Ashleigh J. , Russo Gabriella C. , Si Bishwa R. , Kim Jungwoo , Hoffner Lauren , Jang Cholsoon , Jung Moonjung , Leone Robert D. , Konstantopoulos Konstantinos , Ewald Andrew J. , Wirtz Denis , Jeong Sangmoo
Published: September 2024

Abstract
The loss of E-cadherin, an epithelial cell adhesion molecule, has been implicated in metastasis by mediating the epithelial–mesenchymal transition, which promotes invasion and migration of cancer cells. However, recent studies have demonstrated that E-cadherin supports the survival and proliferation of metastatic cancer cells. Here, we identified a metabolic role for E-cadherin in breast cancer by upregulating the de novo serine synthesis pathway (SSP). The upregulated SSP provided metabolic precursors for biosynthesis and resistance to oxidative stress, enabling E-cadherin+ breast cancer cells to achieve faster tumor growth and enhanced metastases. Inhibition of phosphoglycerate dehydrogenase, a rate-limiting enzyme in the SSP, significantly and specifically hampered proliferation of E-cadherin+ breast cancer cells and rendered them vulnerable to oxidative stress, inhibiting their metastatic potential. These findings reveal that E-cadherin reprograms cellular metabolism, promoting tumor growth and metastasis of breast cancers.

Significance: E-Cadherin promotes the progression and metastasis of breast cancer by upregulating the de novo serine synthesis pathway, offering promising targets for inhibiting tumor growth and metastasis in E-cadherin–expressing tumors.
Supplementary Table S2 from MYTX-011: A pH-Dependent Anti–c-MET Antibody–Drug Conjugate Designed for Enhanced Payload Delivery to c-MET–Expressing Tumor Cells
Authors: Gera Nimish , Fitzgerald Kyle M. , Ramesh Vijay , Patel Purvi , Kanojia Deepak , Colombo Federico , Kien Lena , Aoyama Simon , Xu Lihui , Jean Jussekia , Deshpande Amit M. , Comb William C. , Chittenden Thomas , Fiske Brian P.
Published: September 2024

Cytotoxicity of MYTX-011 across 62 cancer cell lines.
Supplementary Figure S4 from MYTX-011: A pH-Dependent Anti–c-MET Antibody–Drug Conjugate Designed for Enhanced Payload Delivery to c-MET–Expressing Tumor Cells
Authors: Gera Nimish , Fitzgerald Kyle M. , Ramesh Vijay , Patel Purvi , Kanojia Deepak , Colombo Federico , Kien Lena , Aoyama Simon , Xu Lihui , Jean Jussekia , Deshpande Amit M. , Comb William C. , Chittenden Thomas , Fiske Brian P.
Published: September 2024

Total ADC, total mAb and free MMAE levels following a single dose of MYTX-011. Cynomolgus monkeys (n=3 per group) were dosed with 6.0 mg/kg of the respective test articles and total.
Supplementary Table 1 from Radiation and Chemo-Sensitizing Effects of DNA-PK Inhibitors Are Proportional in Tumors and Normal Tissues
Authors: Baker Jennifer H.E. , Kyle Alastair H. , Liu Nannan A. , Wang Taixiang , Liu Xinhe , Teymori Sevin , Banáth Judit P. , Minchinton Andrew I.
Published: September 2024

Experiment details by figure.
Figure S1 from HPN328, a Trispecific T Cell–Activating Protein Construct Targeting DLL3-Expressing Solid Tumors
Authors: Molloy Mary E. , Aaron Wade H. , Barath Manasi , Bush Mabel C. , Callihan Evan C. , Carlin Kevin , Cremin Michael , Evans Thomas , Guerrero Maria G. , Hemmati Golzar , Hundal Avneel S. , Lao Llewelyn , Laurie Payton , Lemon Bryan D. , Lin S.J. , O’Rear Jessica , Patnaik Purbasa , Sotelo Rocha Sony , Santiago Linda , Strobel Kathryn L. , Valenzuela Laura B. , Wu Chi-Heng , Yu Stephen , Yu Timothy Z. , Anand Banmeet S. , Law Che-Leung , Sun Liping L. , Wesche Holger , Austin Richard J.
Published: September 2024

Structure of HPN328.
Supplementary Table 2 from Prognostic Significance of SASP-Related Gene Signature of Radiation Therapy in Head and Neck Squamous Cell Carcinoma
Authors: Lee Min Kyeong , Woo Seon Rang , Noh Joo Kyung , Min Soonki , Kong Moonkyoo , Lee Young Chan , Ko Seong-Gyu , Eun Young-Gyu
Published: September 2024

Supplementary Table 2
Supplementary Figure 7 from Enhancing Neutrophil Cytotoxicity of a Panel of Clinical EGFR Antibodies by Fc Engineering to IgA3.0
Authors: Chan Chilam , Jansen J.H. Marco , Hendriks Ilona S.T. , van der Peet Ida C. , Verdonschot Meggy E.L. , Passchier Elsemieke M. , Tsioumpekou Maria , Nederend Maaike , Klomp Sharon A. , Valerius Thomas , Peipp Matthias , Leusen Jeanette H.W. , Olofsen Patricia A.
Published: September 2024

Supplementary Figure 7: Binding kinetics of IgA3.0 EGFR antibodies.
Data from Radiation and Chemo-Sensitizing Effects of DNA-PK Inhibitors Are Proportional in Tumors and Normal Tissues
Authors: Baker Jennifer H.E. , Kyle Alastair H. , Liu Nannan A. , Wang Taixiang , Liu Xinhe , Teymori Sevin , Banáth Judit P. , Minchinton Andrew I.
Published: September 2024

Abstract
Inhibitors of DNA-dependent protein kinase (PRKDC; DNA-PK) sensitize cancers to radiotherapy and DNA-damaging chemotherapies, with candidates in clinical trials. However, the degree to which DNA-PK inhibitors also sensitize normal tissues remains poorly characterized. In this study, we compare tumor growth control and normal tissue sensitization following DNA-PK inhibitors in combination with radiation and etoposide. FaDu tumor xenografts implanted in mice were treated with 10 to 15 Gy irradiation ± 3 to 100 mg/kg AZD7648. A dose-dependent increase in time to tumor volume doubling following AZD7648 was proportional to an increase in toxicity scores of the overlying skin. Similar effects were seen in the intestinal jejunum, tongue, and FaDu tumor xenografts of mice assessed for proliferation rates at 3.5 days after treatment with etoposide or 5 Gy whole body irradiation ± DNA-PK inhibitors AZD7648 or peposertib (M3814). Additional organs were examined for sensitivity to DNA-PK inhibitor activity in ATM-deficient mice, where DNA-PK activity is indicated by surrogate marker γH2AX. Inhibition was observed in the heart, brain, pancreas, thymus, tongue, and salivary glands of ATM-deficient mice treated with the DNA-PK inhibitors relative to radiation alone. Similar reductions are also seen in ATM-deficient FaDu tumor xenografts where both pDNA-PK and γH2AX staining could be performed. DNA-PK inhibitor-mediated sensitization to radiation and DNA-damaging chemotherapy are not only limited to tumor tissues, but also extends to normal tissues sustaining DNA damage. These data are useful for interpretation of the sensitizing effects of DNA damage repair inhibitors, where a therapeutic index showing greater cell-killing effects on cancer cells is crucial for optimal clinical translation.
Data from HPN328, a Trispecific T Cell–Activating Protein Construct Targeting DLL3-Expressing Solid Tumors
Authors: Molloy Mary E. , Aaron Wade H. , Barath Manasi , Bush Mabel C. , Callihan Evan C. , Carlin Kevin , Cremin Michael , Evans Thomas , Guerrero Maria G. , Hemmati Golzar , Hundal Avneel S. , Lao Llewelyn , Laurie Payton , Lemon Bryan D. , Lin S.J. , O’Rear Jessica , Patnaik Purbasa , Sotelo Rocha Sony , Santiago Linda , Strobel Kathryn L. , Valenzuela Laura B. , Wu Chi-Heng , Yu Stephen , Yu Timothy Z. , Anand Banmeet S. , Law Che-Leung , Sun Liping L. , Wesche Holger , Austin Richard J.
Published: September 2024

Abstract
Delta-like ligand 3 (DLL3) is expressed in more than 70% of small cell lung cancers (SCLCs) and other neuroendocrine-derived tumor types. SCLC is highly aggressive, and limited therapeutic options lead to poor prognosis for patients. HPN328 is a trispecific T cell–activating construct (TriTAC) consisting of three binding domains: a CD3 binder for T-cell engagement, an albumin binder for half-life extension, and a DLL3 binder for tumor cell engagement. In vitro assays, rodent models, and non-human primates were used to assess the activity of HPN328. HPN328 induces potent dose-dependent killing of DLL3-expressing SCLC cell lines in vitro, concomitant with T-cell activation and cytokine release. In an NCI-H82 xenograft model with established tumors, HPN328 treatment led to T-cell recruitment and anti-tumor activity. In an immunocompetent mouse model expressing a human CD3ε epitope, mice previously treated with HPN328 withstood tumor rechallenge, demonstrating long-term anti-tumor immunity. When repeat doses were administered to cynomolgus monkeys, HPN328 was well tolerated up to 10 mg/kg. Pharmacodynamic changes, such as transient cytokine elevation, were observed, consistent with the expected mechanism of action of T-cell engagers. HPN328 exhibited linear pharmacokinetics in the given dose range with a serum half-life of 78 to 187 hours, supporting weekly or less frequent administration of HPN328 in humans. Preclinical and nonclinical characterization suggests that HPN328 is a highly efficacious, safe, and novel therapeutic candidate. A phase 1/2 clinical trial is currently underway testing safety and efficacy in patients with DLL3-expressing malignancies.
Data from IL-15/IL-15Rα-Fc-Fusion Protein XmAb24306 Potentiates Activity of CD3 Bispecific Antibodies through Enhancing T-Cell Expansion
Authors: Li Ji , Clark Robyn , Slaga Dionysos , Avery Kendra , Liu Ke , Schubbert Suzanne , Varma Rajat , Chiang Eugene , Totpal Klara , Bernett Matthew J. , Holder Patrick G. , Junttila Teemu T.
Published: September 2024

Abstract
An insufficient quantity of functional T cells is a likely factor limiting the clinical activity of T-cell bispecific antibodies, especially in solid tumor indications. We hypothesized that XmAb24306 (efbalropendekin alfa), a lymphoproliferative interleukin (IL)-15/IL-15 receptor α (IL-15Rα) Fc-fusion protein, may potentiate the activity of T-cell dependent (TDB) antibodies. The activation of human peripheral T cells by cevostamab, an anti-FcRH5/CD3 TDB, or anti-HER2/CD3 TDB resulted in the upregulation of the IL-2/15Rβ (CD122) receptor subunit in nearly all CD8+ and majority of CD4+ T cells, suggesting that TDB treatment may sensitize T cells to IL-15. XmAb24306 enhanced T-cell bispecific antibody-induced CD8+ and CD4+ T-cell proliferation and expansion. In vitro combination of XmAb24306 with cevostamab or anti-HER2/CD3 TDB resulted in significant enhancement of tumor cell killing, which was reversed when T-cell numbers were normalized, suggesting that T-cell expansion is the main mechanism of the observed benefit. Pretreatment of immunocompetent mice with a mouse-reactive surrogate of XmAb24306 (mIL-15-Fc) resulted in a significant increase of T cells in the blood, spleen, and tumors and converted transient anti-HER2/CD3 TDB responses to complete durable responses. In summary, our results support the hypothesis that the number of tumor-infiltrating T cells is rate limiting for the activity of solid tumor-targeting TDBs. Upregulation of CD122 by TDB treatment and the observed synergy with XmAb24306 and T-cell bispecific antibodies support clinical evaluation of this novel immunotherapy combination.
Supplementary Figure 3 from Hepatitis B Virus X Protein Represses Expression of Tumor Suppressor PTPN18 in Hepatocellular Carcinoma
Authors: Zhou Zhenyu , Yu Wei , Li Huoming , Shi Juanyi , Meng Shiyu , Yan Yongcong , Chen Ruibin , Liu Haohan , Wang Jie , Sun Jian , Xiao Zhiyu , Zhang Jianlong
Published: September 2024

PTPN18 overexpression promotes HCCLM3 migration and proliferation.
Supplementary Figure 1 from Hepatitis B Virus X Protein Represses Expression of Tumor Suppressor PTPN18 in Hepatocellular Carcinoma
Authors: Zhou Zhenyu , Yu Wei , Li Huoming , Shi Juanyi , Meng Shiyu , Yan Yongcong , Chen Ruibin , Liu Haohan , Wang Jie , Sun Jian , Xiao Zhiyu , Zhang Jianlong
Published: September 2024

The expression of PTPNs family members in the HCC-TCGA and GTEx datasets.
Figure S2 from Intrinsic Epigenetic State of Primary Osteosarcoma Drives Metastasis
Authors: Singh Irtisha , Rainusso Nino , Kurenbekova Lyazat , Nirala Bikesh K. , Dou Juan , Muruganandham Abhinaya , Yustein Jason T.
Published: September 2024

Differential expression of RNA-seq between the different groups.
Figure S11 from Mechanisms of Glioblastoma Replication: Ca2+ Flares and Cl− Currents
Authors: Li Yunzhen , Sanchez Triviño Cesar Adolfo , Hernandez Andres , Mortal Simone , Spada Federica , Krivosheia Ilona , Franco Nicoletta , Spelat Renza , Cesselli Daniela , Manini Ivana , Skrap Miran , Menini Anna , Cesca Fabrizia , Torre Vincent
Published: September 2024

Flow cytometry analysis of cell cycle phases for NFA- and CBX-treated U87 cells.
Supplementary Table S7 from miR-497 Target Gene Regulatory Network in Angiosarcoma
Authors: Benton Annaleigh , Moriarty Noah M. , Terwilliger Emma , Liu Bozhi , Murphy Ant , Maluvac Hannah , Shu Mae , Gartenhaus Lauren E. , Janson Nimod D. , Pfeffer Claire M. , Utturkar Sagar M. , Parkinson Elizabeth I. , Lanman Nadia A. , Hanna Jason A.
Published: September 2024

Gene Ontology analysis of miR-497 downregulated genes in ADC106 cells.
Supplementary Figure Legends from Clinically Relevant Humanized Mouse Models of Metastatic Prostate Cancer Facilitate Therapeutic Evaluation
Authors: Kostlan Raymond J. , Phoenix John T. , Budreika Audris , Ferrari Marina G. , Khurana Neetika , Choi Jae E. , Juckette Kristin , Mahapatra Somnath , McCollum Brooke L. , Moskal Russell , Mannan Rahul , Qiao Yuanyuan , Vander Griend Donald J. , Chinnaiyan Arul M. , Kregel Steven
Published: September 2024

Supplementary Figure Legends
Figure S13 from Clinically Relevant Humanized Mouse Models of Metastatic Prostate Cancer Facilitate Therapeutic Evaluation
Authors: Kostlan Raymond J. , Phoenix John T. , Budreika Audris , Ferrari Marina G. , Khurana Neetika , Choi Jae E. , Juckette Kristin , Mahapatra Somnath , McCollum Brooke L. , Moskal Russell , Mannan Rahul , Qiao Yuanyuan , Vander Griend Donald J. , Chinnaiyan Arul M. , Kregel Steven
Published: September 2024

IHC of AR and PD1 of 22Rv1 tumors in huNOG-EXL mice.
Supplementary Data from miR-497 Target Gene Regulatory Network in Angiosarcoma
Authors: Benton Annaleigh , Moriarty Noah M. , Terwilliger Emma , Liu Bozhi , Murphy Ant , Maluvac Hannah , Shu Mae , Gartenhaus Lauren E. , Janson Nimod D. , Pfeffer Claire M. , Utturkar Sagar M. , Parkinson Elizabeth I. , Lanman Nadia A. , Hanna Jason A.
Published: September 2024

Supplementary data information and methods
Figure S11 from Clinically Relevant Humanized Mouse Models of Metastatic Prostate Cancer Facilitate Therapeutic Evaluation
Authors: Kostlan Raymond J. , Phoenix John T. , Budreika Audris , Ferrari Marina G. , Khurana Neetika , Choi Jae E. , Juckette Kristin , Mahapatra Somnath , McCollum Brooke L. , Moskal Russell , Mannan Rahul , Qiao Yuanyuan , Vander Griend Donald J. , Chinnaiyan Arul M. , Kregel Steven
Published: September 2024

Immune-profile of spleen and tumor B-cell Populations and B-cell activation NK-Cell population in huNOG-EXL spleen.
Table S3 from MLLT6/ATF2 Axis Restrains Breast Cancer Progression by Driving DDIT3/4 Expression
Authors: Yu Qing , Zhao Jiayi , Yang Anli , Li Xiangxin
Published: September 2024

The sequence of primers used for Ch-IP qPCR
Figure S1 from MLLT6/ATF2 Axis Restrains Breast Cancer Progression by Driving DDIT3/4 Expression
Authors: Yu Qing , Zhao Jiayi , Yang Anli , Li Xiangxin
Published: September 2024

Supplementary Figure S1, referred to Figure 1.
Supplemental Table 1 from Diet Modulates the Gut Microbiome, Metabolism, and Mammary Gland Inflammation to Influence Breast Cancer Risk
Authors: Arnone Alana A. , Wilson Adam S. , Soto-Pantoja David R. , Cook Katherine L.
Published: September 2024

Supplemental Table 1: Fecal 16S Genus-Level abundance from non-tumor bearing mice fed different diets
Supplementary Table S2 from CHD2 Regulates Neuron–Glioma Interactions in Pediatric Glioma
Authors: Zhang Xu , Duan Shoufu , Apostolou Panagiota E. , Wu Xiaoping , Watanabe Jun , Gallitto Matthew , Barron Tara , Taylor Kathryn R. , Woo Pamelyn J. , Hua Xu , Zhou Hui , Wei Hong-Jian , McQuillan Nicholas , Kang Kyung-Don , Friedman Gregory K. , Canoll Peter D. , Chang Kenneth , Wu Cheng-Chia , Hashizume Rintaro , Vakoc Christopher R. , Monje Michelle , McKhann Guy M. , Gogos Joseph A. , Zhang Zhiguo
Published: September 2024

Analysis for DEGs of CHD2-depleted H3.1K27M DMG cells.
Supplementary Figure S15 from Molecular Determinants of Sensitivity to Polatuzumab Vedotin in Diffuse Large B-Cell Lymphoma
Authors: Corcoran Sean R. , Phelan James D. , Choi Jaewoo , Shevchenko Galina , Fenner Rachel E. , Yu Xin , Scheich Sebastian , Hsiao Tony , Morris Vivian M. , Papachristou Evangelia K. , Kishore Kamal , D’Santos Clive S. , Ji Yanlong , Pittaluga Stefania , Wright George W. , Urlaub Henning , Pan Kuan-Ting , Oellerich Thomas , Muppidi Jagan , Hodson Daniel J. , Staudt Louis M.
Published: September 2024

CD79B is degraded in a lysosomal, not proteasomal manner
Supplementary Figure S11 from Molecular Determinants of Sensitivity to Polatuzumab Vedotin in Diffuse Large B-Cell Lymphoma
Authors: Corcoran Sean R. , Phelan James D. , Choi Jaewoo , Shevchenko Galina , Fenner Rachel E. , Yu Xin , Scheich Sebastian , Hsiao Tony , Morris Vivian M. , Papachristou Evangelia K. , Kishore Kamal , D’Santos Clive S. , Ji Yanlong , Pittaluga Stefania , Wright George W. , Urlaub Henning , Pan Kuan-Ting , Oellerich Thomas , Muppidi Jagan , Hodson Daniel J. , Staudt Louis M.
Published: September 2024

Knockout of the E3 ligase KLHL6 results in increased cell surface CD79B in a human model of GCB DLBCL
Supplementary Table S1 from Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: a Report from the Children’s Oncology Group
Authors: Stieglitz Elliot , Lee Alex G. , Angus Steven P. , Davis Christopher , Barkauskas Donald A. , Hall David , Kogan Scott C. , Meyer Julia , Rhodes Steven D. , Tasian Sarah K. , Xuei Xiaoling , Shannon Kevin , Loh Mignon L. , Fox Elizabeth , Weigel Brenda J.
Published: September 2024

Demographics.
Supplementary Figure S1 from Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: a Report from the Children’s Oncology Group
Authors: Stieglitz Elliot , Lee Alex G. , Angus Steven P. , Davis Christopher , Barkauskas Donald A. , Hall David , Kogan Scott C. , Meyer Julia , Rhodes Steven D. , Tasian Sarah K. , Xuei Xiaoling , Shannon Kevin , Loh Mignon L. , Fox Elizabeth , Weigel Brenda J.
Published: September 2024

Survival Curve.
Supplementary Table S16 from A Functional Survey of the Regulatory Landscape of Estrogen Receptor–Positive Breast Cancer Evolution
Authors: Barozzi Iros , Slaven Neil , Canale Eleonora , Lopes Rui , Amorim Monteiro Barbosa Inês , Bleu Melusine , Ivanoiu Diana , Pacini Claudia , Mensa’ Emanuela , Chambers Alfie , Bravaccini Sara , Ravaioli Sara , Győrffy Balázs , Dieci Maria Vittoria , Pruneri Giancarlo , Galli Giorgio Giacomo , Magnani Luca
Published: September 2024

Supplementary Table S16: Downstream analyses considering only the SIDV inferred genetic alterations with predicted impact on function. S16.1: results of the binomial enrichment test. SID regions overlapping at least 2 SNVs predicted as pathogenic are included. Along with genomic coordinates (hg38) the total number of SNVs as well as the number of predicted pathogenic SNVs overlapping the region are indicated. The p-value and the q-value (after Benjamini-Hochberg correction) of the binomial test are indicated, along with annotation to the closest gene. The 63 regions considered for further analyses are highlighted in red. S16.2: same as S13.1 but considering all the regions assigned to the genes annotated to the same ontological terms together. The number and identity of the genes contributing to the overlap are indicated, along with p-value of the binomial test, and the q-value (after Benjamini-Hochberg correction). Statistically significant terms (q-value <= 0.05) are highlighted in red. S16.3: results of the analyses testing for the enrichment of mutations (either SNVs, short INDELs, or both; mutation_type column) with computationally predicted pathogenic effects in the sets of regions also showing a certain behavior in SIDP (CRISPRi_hit_type column). Observed and expected overlap are indicated, along with the odds ratio and the p-value (Chi-squared test).
Supplementary Table S14 from A Functional Survey of the Regulatory Landscape of Estrogen Receptor–Positive Breast Cancer Evolution
Authors: Barozzi Iros , Slaven Neil , Canale Eleonora , Lopes Rui , Amorim Monteiro Barbosa Inês , Bleu Melusine , Ivanoiu Diana , Pacini Claudia , Mensa’ Emanuela , Chambers Alfie , Bravaccini Sara , Ravaioli Sara , Győrffy Balázs , Dieci Maria Vittoria , Pruneri Giancarlo , Galli Giorgio Giacomo , Magnani Luca
Published: September 2024

Supplementary Table S14: Datasets used for the training of the TF-specific deltaSVM models. For each TF, the corresponding gene symbol, along with information about the cells from which the ChIP-seq binding profile was obtained, the treatment the cells were exposed to (if any), and reference to the corresponding records on the Gene Expression Omnibus, are indicated. Information about the matched, high-quality position weight matrix (PWM) utilized as source of information to infer the binding affinities of each TF is also provided. For each PWM, an identifier is indicated, along with the corresponding reference database or publication (including Pubmed ID).