bluuebunny/crossref_metadata_2025 huggingface dataset:
Stenting versus medical treatment alone for symptomatic intracranial artery stenosis: a preplanned pooled individual patient data analysis
Authors: Wang Tao , Luo Jichang , Li Tianhua , Almallouhi Eyad , Gao Peng , Gong Haozhi , Zhang Xiao , Wang Jie , Lu Taoyuan , Yang Yifan , Yang Renjie , Xing Zixuan , Wang Haibo , Derdeyn Colin P , Jiao Liqun
Published: August 2024

Background

Whether the safety and efficacy of percutaneous transluminal angioplasty and stenting (PTAS) is significantly different from that of medical treatment alone for symptomatic intracranial arterial stenosis (ICAS) is debatable. A study was undertaken to determine the safety and eﬀicacy of both treatments for symptomatic ICAS.

Methods

This preplanned pooled individual patient data analysis included 400 participants treated with PTAS and 409 treated with medical treatment alone in two large multicenter randomized clinical trials (SAMMPRIS and CASSISS). Patients were treated with PTAS using a self-expanding stent or medical treatment alone. The primary outcome was stroke or death within 30 days, or ischemic stroke in the territory of the qualifying artery more than 30 days after enrollment.

Results

Individual data were obtained for 809 patients, 451 from SAMMPRIS and 358 from CASSISS. 400 participants were randomly assigned to the PTAS group and 409 to the medical group. The risk of the primary outcome was not significant between the PTAS and medical groups (17.5% vs 13.2%; HR 1.37 (95% CI 0.96 to 1.95), P=0.08). However, the risk of stroke or death within 30 days was higher in the PTAS group (10.5% vs 4.2%; HR 2.62 (95% CI 1.49 to 4.61), P<0.001). Patients of white ethnicity (HR 1.97, 95% CI 1.17 to 3.31) and those with hyperlipidemia (HR 2.04, 95% CI 1.27 to 3.26) or a transient ischemic attack (TIA) (HR 2.19, 95% CI 1.08 to 4.45) were at higher risk for PTAS.

Conclusions

PTAS poses an increased risk of short-term stroke/death and therefore is not advised as primary treatment for symptomatic ICAS. A balance exists between stroke risks and revascularization benefits. For patients with asymptomatic ICAS of white ethnicity and those with hyperlipidemia or a history of TIA, a thorough assessment is warranted before considering PTAS.

Trial registration

ClinicalTrials.gov Identifier:NCT00576693,NCT01763320.
A Comparison of the Effects of Dairy Products with their Plant-based Alternatives on Metabolic Responses in Healthy Young Canadian Adults: a randomized cross-over study
Authors: Da Silva Nicole , Anderson G. Harvey , Amr Amira M. , Vien Shirley , Fabek Hrvoje
Published: August 2024

Plant-based food demand is rapidly increasing. However, the metabolic responses of plant proteins within their commercially available form remains unclear. Two randomized crossover experiments compared plant-based alternatives to dairy on postprandial glycemia, metabolic hormones, and appetite before and after a fixed size (12 kcal/kg body weight) pasta meal in sixteen healthy young adults (eight males and eight females). In experiment one, participants (22.8±2.3y) consumed one-serving of Greek yogurt (175g), cheddar cheese (30g), plant-based cheese (30g), or plant-based yogurt (175g). In experiment two, participants (22.3±2.4y) consumed one-serving (250 mL) of cow’s milk, vanilla soy beverage or vanilla almond beverage, and (30 g) of cheddar cheese or plant-based cheese. Blood glucose, insulin, and appetite were measured at baseline, post-treatment, and following a fixed-size pasta meal (post-meal) within 15-30 min. In experiment two, C-peptide, GLP-1, and ghrelin were measured. Greek yogurt and cheddar cheese lowered post-meal blood glucose more than their plant-based alternatives (p <0.01) and post-treatment blood glucose was higher following almond beverage than cheddar cheese and plant-based cheese (p <0.01). In experiment 1, post-treatment insulin was higher after Greek yogurt than cheddar cheese and plant-based cheese and all treatments post-meal (p <0.02). Post-meal appetite was lower after plant-based yogurt than cheddar cheese and plant-based cheese (p <0.01). In experiment 2, post-treatment insulin was higher after almond beverage compared to all treatments (p <0.01) and post-meal GLP-1 was higher after milk than almond beverage (p =0.03). We conclude that the physiological functionality of plant-based alternatives as measured by blood glucose, insulin, C-peptide, and GLP-1 did not replicate the metabolic functions of dairy products.
Paired comparisons with quiet surface drones show evidence of fish behavioral response to motorized vessels during acoustic surveys in Lake Superior
Authors: Evans Thomas M. , Rudstam Lars G. , Sethi Suresh A. , Yule Daniel L. , Warner David M. , Farha Steven A. , Barnard Andrew R. , DuFour Mark R. , O’Brien Timothy P. , Nasworthy Kayden C. , Harding Ian , Ray Bradley A. , Isaac Edmund , Blankenheim Joshua , Blair Hannah B. , Watkins James M. , Senczyszyn Steven A. , Roberts James J. , Esselman Peter C.
Published: August 2024

Acoustic surveys are important for fish stock assessments, but fish responses to survey vessels can bias acoustic estimates. We leveraged quiet uncrewed surface vessels (USVs) to characterize potential bias in acoustic surveys. Five conventional motorized ships overtook USVs from astern over 2 km transects at night in Lake Superior in 2022. We examined the difference in acoustic backscatter, average target depth, and average target strength (TS) between USV and motorized vessels. Although sound level measurements from the motorized vessels sometimes exceeded recommendations for scientific vessels, we did not detect differences in acoustic measures among survey vessels. However, the USVs recorded 2 dB higher acoustic backscatter and TS than motorized vessels, leading to ∼15% higher fish densities with drones when using in situ TS and echo integration. Differences in fish density would increase to 30%–60% if a standard TS value was applied. Target depth did not differ between USVs and motorized ships. These results are consistent with a change in orientation but not depth of insonified fish and limited horizontal avoidance of motorized survey vessels.
Story of Your Lazy Function’s Life: A Bidirectional Demand Semantics for Mechanized Cost Analysis of Lazy Programs
Authors: Xia Li-yao , Israel Laura , Kramarz Maite , Coltharp Nicholas , Claessen Koen , Weirich Stephanie , Li Yao
Published: August 2024

Lazy evaluation is a powerful tool that enables better compositionality and potentially better performance in functional programming, but it is challenging to analyze its computation cost. Existing works either require manually annotating sharing, or rely on separation logic to reason about heaps of mutable cells. In this paper, we propose a bidirectional demand semantics that allows for extrinsic reasoning about the computation cost of lazy programs without relying on special program logics. To show the effectiveness of our approach, we apply the demand semantics to a variety of case studies including insertion sort, selection sort, Okasaki's banker's queue, and the implicit queue. We formally prove that the banker's queue and the implicit queue are both amortized and persistent using the Rocq Prover (formerly known as Coq). We also propose the reverse physicist's method, a novel variant of the classical physicist's method, which enables mechanized, modular and compositional reasoning about amortization and persistence with the demand semantics.
Compiled, Extensible, Multi-language DSLs (Functional Pearl)
Authors: Ballantyne Michael , Gamburg Mitch , Hemann Jason
Published: August 2024

Implementations of domain-specific languages should offer both extensibility and performance optimizations. With the new syntax-spec metalanguage in Racket, programmers can easily create DSL implementations that are both automatically macro-extensible and subject to conventional compiler optimizations. This pearl illustrates this approach through a new implementation of miniKanren, a widely used relational programming DSL. The miniKanren community has explored, in separate implementations, optimization techniques and a wide range of extensions. We demonstrate how our new miniKanren implementation with syntax-spec reconciles these features in a single implementation that comes with both an optimizing compiler and an extension mechanism. Furthermore, programmers using the new implementation benefit from the same seamless integration between Racket and miniKanren as in existing shallow embeddings.
On the Operational Theory of the CPS-Calculus: Towards a Theoretical Foundation for IRs
Authors: Torrens Paulo , Orchard Dominic , Vasconcellos Cristiano
Published: August 2024

The continuation-passing style translation often employed by compilers gives rise to a class of intermediate representation languages where functions are not allowed to return anymore. Though the primary use of these intermediate representation languages is to expose details about a program's control flow, they may be equipped with an equational theory in order to be seen as specialized calculi, which in turn may be related to the original languages by means of a factorization theorem. In this paper, we explore Thielecke's CPS-calculus, a small theory of continuations inspired by compiler implementations, and study its metatheory. We extend it with a sound reduction semantics that faithfully represents optimization rules used in actual compilers, and prove that it acts as a suitable theoretical foundation for the intermediate representation of Appel's and Kennedy's compilers by following the guidelines set out by Plotkin. Finally, we prove that the CPS-calculus is strongly normalizing in the simply typed setting by using a novel proof method for reasoning about reducibility at a distance, from which logical consistency follows. Taken together, these results close a gap in the existing literature, providing a formal theory for reasoning about intermediate representations.
Almost-Sure Termination by Guarded Refinement
Authors: Gregersen Simon Oddershede , Aguirre Alejandro , Haselwarter Philipp G. , Tassarotti Joseph , Birkedal Lars
Published: August 2024

Almost-sure termination is an important correctness property for probabilistic programs, and a number of program logics have been developed for establishing it. However, these logics have mostly been developed for first-order programs written in languages with specific syntactic patterns for looping. In this paper, we consider almost-sure termination for higher-order probabilistic programs with general references. This combination of features allows for recursion and looping to be encoded through a variety of patterns. Therefore, rather than developing proof rules for reasoning about particular recursion patterns, we instead propose an approach based on proving refinement between a higher-order program and a simpler probabilistic model, in such a way that the refinement preserves termination behavior. By proving a refinement, almost-sure termination behavior of the program can then be established by analyzing the simpler model.

We present this approach in the form of Caliper, a higher-order separation logic for proving termination-preserving refinements. Caliper uses probabilistic couplings to carry out relational reasoning between a program and a model. To handle the range of recursion patterns found in higher-order programs, Caliper uses guarded recursion, in particular the principle of Löb induction. A technical novelty is that Caliper does not require the use of transfinite step indexing or other technical restrictions found in prior work on guarded recursion for termination-preservation refinement. We demonstrate the flexibility of this approach by proving almost-sure termination of several examples, including first-order loop constructs, a random list generator, treaps, and a sampler for Galton-Watson trees that uses higher-order store. All the results have been mechanized in the Coq proof assistant.
Functional Programming in Financial Markets (Experience Report)
Authors: Dijkstra Atze , Magalhães José Pedro , Néron Pierre
Published: August 2024

We present a case-study of using functional programming in the real world at a very large scale. At

Standard Chartered Bank, Haskell is used in a core software library supporting the entire

Markets division -- a business line with 3 billion USD operating income in 2023.

Typed functional programming is used across the entire tech stack, including foundational APIs and CLIs for deal

valuation and risk analysis, server-side components for long-running batches or sub-second RESTful services, and

end-user GUIs. Thousands of users across Markets interact with software built using functional programming,

and over one hundred write functional code.

In this experience report we focus on how we leverage functional programming to orchestrate type-driven large-scale

pricing workflows. The same API can be used to price one trade locally, or millions of trades across thousands of

cloud nodes. Different parts of the computation can be run and inspected individually, and recomputing one part

triggers recalculation of the dependent parts only. We build upon decades of research and experience in the

functional programming community, relying on concepts such as monads, lenses, datatype generics, and closure

serialisation. We conclude that the use of functional programming is one of the main drivers of the success

of our project, and we see no significant downsides from it.
Blame-Correct Support for Receiver Properties in Recursively-Structured Actor Contracts
Authors: Vandenbogaerde Bram , Stiévenart Quentin , De Roover Coen
Published: August 2024

Actor languages model concurrency as processes that communicate through asynchronous message sends.Unfortunately, as the complexity of these systems increases, it becomes more difficult to compose and integrate their components. This is because of assumptions made by components about their communication partners which may not be upheld when they remain implicit. In this paper, we bring design-by-contract programming to actor programs through a contract system that enables expressing constraints on receiver-related properties.Expressing properties about the expected receiver of a message, and about this receiver's communication behavior, requires two novel types of contracts.Through their recursive structure, these contracts can govern entire communication chains. We implement the contract system for an actor extension of Scheme, describe it formally, and show how to assign blame in case of a contract violation.Finally, we prove our contract system and its blame assignment correct by formulating and proving a blame correctness theorem.
Refinement Composition Logic
Authors: Song Youngju , Lee Dongjae
Published: August 2024

One successful approach to verifying programs is refinement, where one establishes that the implementation (e.g., in C) behaves as specified in its mathematical specification. In this approach, the end result (a whole implementation refines a whole specification) is often established via composing multiple “small” refinements.

In this paper, we focus on the task of composing refinements. Our key observation is a novel correspondence between the task of composing refinements and the task of proving entailments in modern separation logic. This correspondence is useful. First, it unlocks tools and abstract constructs developed for separation logic, greatly streamlining the composition proof. Second, it uncovers a fundamentally new verification strategy. We address the key challenge in establishing the correspondence with a novel use of angelic non-determinism.

Guided by the correspondence, we develop RCL (Refinement Composition Logic), a logic dedicated to composing refinements. All our results are formalized in Coq.
Deriving with Derivatives: Optimizing Incremental Fixpoints for Higher-Order Flow Analysis
Authors: Quiring Benjamin , Van Horn David
Published: August 2024

At the heart of efficient program analysis implementations are incremental solutions to fixpoint problems. These solutions can be interpreted as the derivative of the underlying analysis function. Methods that describe how to systematically derive higher-order analyses from program semantics, such as Abstracting Abstract Machines,
don’t
shed light on how to efficiently
implement
those analyses. In this paper, we explore complementary techniques to optimize the derivative computation towards deriving efficient implementations. In particular, we use static specializations (by partial evaluation and rewriting) and dynamic specializations (in the form of tracking dependencies during the fixpoint), yielding efficient incremental fixpoints. We present how these optimizations apply to an example analysis of continuation-passing-style λ-calculus, and describe how they pair particularly well with tunable and optimized workset-based fixpoint methods. We demonstrate the efficacy of this approach on a flow analysis for the Standard ML language, yielding an average speed-up of 56x over an existing fixpoint method for higher-order analyses from the literature.
A Two-Phase Infinite/Finite Low-Level Memory Model: Reconciling Integer–Pointer Casts, Finite Space, and undef at the LLVM IR Level of Abstraction
Authors: Beck Calvin , Yoon Irene , Chen Hanxi , Zakowski Yannick , Zdancewic Steve
Published: August 2024

This paper provides a novel approach to reconciling complex low-level memory model features, such as pointer--integer casts, with desired refinements that are needed to justify the correctness of program transformations. The idea is to use a "two-phase" memory model, one with an unbounded memory and corresponding unbounded integer type, and one with a finite memory; the connection between the two levels is made explicit by a notion of refinement that handles out-of-memory behaviors. This approach allows for more optimizations to be performed and establishes a clear boundary between the idealized semantics of a program and the implementation of that program on finite hardware.

The two-phase memory model has been incorporated into an LLVM IR semantics, demonstrating its utility in practice in the context of a low-level language with features like undef and bitcast. This yields infinite and finite memory versions of the language semantics that are proven to be in refinement with respect to out-of-memory behaviors. Each semantics is accompanied by a verified executable reference interpreter. The semantics justify optimizations, such as dead-alloca-elimination, that were previously impossible or difficult to prove correct.
Automated Verification of Higher-Order Probabilistic Programs via a Dependent Refinement Type System
Authors: Kura Satoshi , Unno Hiroshi
Published: August 2024

Verification of higher-order probabilistic programs is a challenging problem. We present a verification method that supports several quantitative properties of higher-order probabilistic programs. Usually, extending verification methods to handle the quantitative aspects of probabilistic programs often entails extensive modifications to existing tools, reducing compatibility with advanced techniques developed for qualitative verification. In contrast, our approach necessitates only small amounts of modification, facilitating the reuse of existing techniques and implementations. On the theoretical side, we propose a dependent refinement type system for a generalised higher-order fixed point logic (HFL). Combined with continuation-passing style encodings of properties into HFL, our dependent refinement type system enables reasoning about several quantitative properties, including weakest pre-expectations, expected costs, moments of cost, and conditional weakest pre-expectations for higher-order probabilistic programs with continuous distributions and conditioning. The soundness of our approach is proved in a general setting using a framework of categorical semantics so that we don’t have to repeat similar proofs for each individual problem. On the empirical side, we implement a type checker for our dependent refinement type system that reduces the problem of type checking to constraint solving. We introduce
admissible predicate variables
and
integrable predicate variables
to constrained Horn clauses (CHC) so that we can soundly reason about the least fixed points and samplings from probability distributions. Our implementation demonstrates that existing CHC solvers developed for non-probabilistic programs can be extended to a solver for the extended CHC with only small efforts. We also demonstrate the ability of our type checker to verify various concrete examples.
Formation of Through-Hole Porous Anodic Aluminum Oxide Layer Locally with 3D Printed Solution Flow Type Microdroplet Cell
Authors: Ayalew Adane Adugna , Han Xiaole , Govindaraj Yoganandan , Sakairi Masatoshi
Published: August 2024

In this study, a 3D-prinited solution-flow type microdroplet cell (SF-MDC) is employed as a new technique for the fabrication of porous anodic aluminum oxide (AAO) layer using oxalic acid electrolyte on aluminum. The surface morphology of the porous AAO film was characterized by a scanning electron microscope. The aim of this study was to fabricate a through-hole porous alumina layer in a single step anodizing process and to investigate the influence of anodized voltages and scanning speeds on the thickness and pore structure of alumina layer. The results showed that the pore diameter and interpore distance were directly proportional to the anodizing voltage. The thicknesses of formed AAO films were found to be 35.5, 50.7, and 81.6 μm at scanning speeds of 10, 5, and 2.5 μms−1, respectively. Through-hole porous AAO was successfully fabricated at room temperature without chemical etching. The SF-MDC fabrication technique is proposed as an environmentally attractive and suitable process for the fabrication of porous AAO layers.
Activity and Selectivity in the Electrochemical Reduction of CO2 at CuSnx Electrocatalysts Using a Zero-Gap Membrane Electrode Assembly
Authors: Dauda Monsuru , Hendershot John , Bello Mustapha , Park Junghyun , Orduz Alvaro Loaiza , Kizilkaya Orhan , Sprunger Phillip , Engler Anthony , Yao Koffi , Plaisance Craig , Flake John
Published: August 2024

In this study Cu, Sn, and bimetallic CuSnx nanoparticles were synthesized and evaluated as electrocatalysts for CO2 reduction using zero gap membrane electrode assemblies. Results show bimetallic electrocatalysts with Sn contents above 10% yield formate as a primary product with Faradaic Efficiencies near 70% at 350 mA cm−2. Cu-Snx electrocatalysts with less than 10% Sn yield CO at current densities below 350 mA cm−2 and relatively lower cell potentials. When the low-Sn content bimetallic electrocatalysts were evaluated in alkaline anolytes at 350 mA cm−2, ethanol was recorded as the primary product (FE = 48.5% at Ecell ≥ 3.0 V). We propose enhanced C2 activity and selectivity originate from Cu dimers adjacent to Sn atoms for bimetallic electrocatalyst with low-Sn content. The C2 active sites are lost when the surface Sn content exceeds 25%–38%.
Structural and Optical Properties of Magnetron-Sputtered Chromium Oxynitride Thin Films
Authors: Khalil Maria , Bashir Aneeqa , Khalil Umara , Ullah Farman , Ramay Shahid M. , Saleem Murtaza
Published: August 2024

Doping non-metal elements into Cr2O3 can tailor its properties, making it more efficient for applications like sensors or photocatalysis. For this purpose, the current research work presents the impact of nitrogen doping on the structural and optical properties of Cr2O3 thin films. Pure and N-doped Cr2O3 (Cr2O3−xNx) thin films were synthesized using the DC reactive magnetron sputtering approach. The stoichiometry was obtained by raising values of x, where x = 0, 0.125, 0.25, and 0.50. X-ray diffraction analysis confirmed the rhombohedral crystal structure without the presence of any other secondary phase in undoped and N-doped Cr2O3 thin films. Furthermore, crystallinity and average crystallite size have enhanced by doping. Field emission scanning electron micrographs disclosed that the surface morphology of the prepared samples changed considerably with doping. A thorough optical investigation was carried out by spectroscopic ellipsometry. Several optical properties significantly changed with dopant content. The reduction in the optical bandgap from 2.50 eV to 1.82 eV, with N-doping was observed. The study demonstrated that N-doping improves the structural and optical properties that make it a promising candidate for optoelectronic applications.
Effect of Film Thickness on the Electrical Resistivity and Optical Functions Distribution of Iron Tris(8-hydroxyquinoline) Thin Films
Authors: El-Khalawany L. M. , Gad S. A. , Moustafa A. M. , Nassar A. , El-Menyawy E. M.
Published: August 2024

Iron tris(8-hydroxyquinoline) (Feq3) was synthesized and investigated by X-ray photoemission spectroscopy. It crystalizes in triclinic polycrystalline structure in powder form, whereas the Feq3 films, with different thickness values (12, 20, 35, and 42 nm), have an amorphous structure. The influence of film thickness on the electrical resistivity and the optical properties is reported. The morphology of Feq3 was investigated in terms of field-emission scanning electron microscope. Electrical resistivity measurements indicate an inverse proportionality to the film thickness. The optical properties of Feq3 films were investigated in terms of photoluminescence spectra and spectrophotometric measurements of transmittance and reflectance. The optical functions such as absorption coefficient and refractive index of the films were calculated. The dependence of the Feq3 film thickness on the optical energy band gap and dispersion parameters was studied. The outcomes indicate that the Feq3 films are of great importance for applications in organic solar cells and light emitting diodes.
Pathophysiology of syncope: current concepts and their development
Authors: Benditt David G. , Fedorowski Artur , Sutton Richard , van Dijk J. Gert
Published: August 2024

Syncope is a symptom in which transient loss of consciousness occurs as a consequence of a self-limited, spontaneously terminating period of cerebral hypoperfusion. Many circulatory disturbances (e.g. brady- or tachyarrhythmias, reflex cardioinhibition-vasodepression-hypotension) may trigger a syncope or near-syncope episode, and identifying the cause(s) is often challenging. Some syncope may involve multiple etiologies operating in concert, whereas in other cases multiple syncope events may be due to various differing causes at different times. In this communication, we address the current understanding of the principal contributors to syncope pathophysiology including examination of the manner in which concepts evolved, an overview of factors that constitute consciousness and loss of consciousness, and aspects of neurovascular control and communication that are impacted by cerebral hypoperfusion leading to syncope. Emphasis focuses on 1) current understanding of the way transient systemic hypotension impacts brain blood flow and brain function; 2) the complexity and temporal sequence of vascular, humoral, and cardiac factors that may accompany the most common causes of syncope; 3) the range of circumstances and disease states that may lead to syncope; and 4) clinical features associated with syncope and in particular the reflex syncope syndromes.
The neurobiology of parenting and infant-evoked aggression
Authors: Kaplan Harris S. , Horvath Patricia M. , Rahman Mohammed Mostafizur , Dulac Catherine
Published: August 2024

Parenting behavior comprises a variety of adult-infant and adult-adult interactions across multiple timescales. The state transition from nonparent to parent requires an extensive reorganization of individual priorities and physiology and is facilitated by combinatorial hormone action on specific cell types that are integrated throughout interconnected and brainwide neuronal circuits. In this review, we take a comprehensive approach to integrate historical and current literature on each of these topics across multiple species, with a focus on rodents. New and emerging molecular, circuit-based, and computational technologies have recently been used to address outstanding gaps in our current framework of knowledge on infant-directed behavior. This work is raising fundamental questions about the interplay between instinctive and learned components of parenting and the mutual regulation of affiliative versus agonistic infant-directed behaviors in health and disease. Whenever possible, we point to how these technologies have helped gain novel insights and opened new avenues of research into the neurobiology of parenting. We hope this review will serve as an introduction for those new to the field, a comprehensive resource for those already studying parenting, and a guidepost for designing future studies.
Supplementary Data 3 from Increased Protein Kinase A Activity Induces Fibrolamellar Hepatocellular Carcinoma Features Independent of DNAJB1
Authors: Shirani Mahsa , Levin Solomon , Shebl Bassem , Requena David , Finkelstein Tova M. , Johnson Daniel S. , Ng Denise , Lalazar Gadi , Heissel Søren , Hojrup Peter , Molina Henrik , de Jong Ype P. , Rice Charles M. , Singhi Aatur D. , Torbenson Michael S. , Coffino Philip , Lyons Barbara , Simon Sanford M.
Published: August 2024

The Spatial transcriptomics data from figure 7 with the cell by cell data for the transcripts of Cyp3A, Muc13 and Col11A1
Video S7 from CENP-E Inhibition Induces Chromosomal Instability and Synergizes with Diverse Microtubule-Targeting Agents in Breast Cancer
Authors: Tucker John B. , Carlsen Caleb L. , Scribano Christina M. , Pattaswamy Srishrika M. , Burkard Mark E. , Weaver Beth A.
Published: August 2024

Normal mitosis
Video S5 from CENP-E Inhibition Induces Chromosomal Instability and Synergizes with Diverse Microtubule-Targeting Agents in Breast Cancer
Authors: Tucker John B. , Carlsen Caleb L. , Scribano Christina M. , Pattaswamy Srishrika M. , Burkard Mark E. , Weaver Beth A.
Published: August 2024

Multipolar spindle that focuses into a bipolar spindle early in mitosis, prior to anaphase onset
Video S4 from CENP-E Inhibition Induces Chromosomal Instability and Synergizes with Diverse Microtubule-Targeting Agents in Breast Cancer
Authors: Tucker John B. , Carlsen Caleb L. , Scribano Christina M. , Pattaswamy Srishrika M. , Burkard Mark E. , Weaver Beth A.
Published: August 2024

Multipolar spindle that is maintained throughout mitosis (no focusing)
Supplementary Fig. S6 from FBXO32 Stimulates Protein Synthesis to Drive Pancreatic Cancer Progression and Metastasis
Authors: Su Dan , Wang Ruobing , Chen Guangyu , Ding Chen , Liu Yueze , Tao Jinxin , Wang Yuanyang , Qiu Jiangdong , Luo Wenhao , Weng Guihu , Yang Gang , Zhang Taiping
Published: August 2024

Supplementary Fig. S6
Supplementary Fig. S4 from FBXO32 Stimulates Protein Synthesis to Drive Pancreatic Cancer Progression and Metastasis
Authors: Su Dan , Wang Ruobing , Chen Guangyu , Ding Chen , Liu Yueze , Tao Jinxin , Wang Yuanyang , Qiu Jiangdong , Luo Wenhao , Weng Guihu , Yang Gang , Zhang Taiping
Published: August 2024

Supplementary Fig. S4
Supplementary Data from The DRAP1/DR1 Repressor Complex Increases mTOR Activity to Promote Progression and Confer Everolimus Sensitivity in Triple-Negative Breast Cancer
Authors: Huang Min-Ying , Hu Shu-Yuan , Dong Jia , Deng Ling , Andriani Lisa , Ma Xiao-Yan , Zhang Yin-Ling , Zhang Fang-Lin , Shao Zhi-Ming , Li Da-Qiang
Published: August 2024

This Supplementary Information includes Supplementary Fig. S1 to S15 and Supplementary Tables S1 to S7.
Supplementary Fig. S26 from FBXO32 Stimulates Protein Synthesis to Drive Pancreatic Cancer Progression and Metastasis
Authors: Su Dan , Wang Ruobing , Chen Guangyu , Ding Chen , Liu Yueze , Tao Jinxin , Wang Yuanyang , Qiu Jiangdong , Luo Wenhao , Weng Guihu , Yang Gang , Zhang Taiping
Published: August 2024

Supplementary Fig. S26
Supplementary Fig. S11 from FBXO32 Stimulates Protein Synthesis to Drive Pancreatic Cancer Progression and Metastasis
Authors: Su Dan , Wang Ruobing , Chen Guangyu , Ding Chen , Liu Yueze , Tao Jinxin , Wang Yuanyang , Qiu Jiangdong , Luo Wenhao , Weng Guihu , Yang Gang , Zhang Taiping
Published: August 2024

Supplementary Fig. S11
Data from Serine Depletion Promotes Antitumor Immunity by Activating Mitochondrial DNA-Mediated cGAS-STING Signaling
Authors: Saha Suchandrima , Ghosh Monisankar , Li Jinyu , Wen Asher , Galluzzi Lorenzo , Martinez Luis A. , Montrose David C.
Published: August 2024

Abstract
Serine is critical for supporting cancer metabolism, and depriving malignant cells of this nonessential amino acid exerts antineoplastic effects, in large part, through disrupting metabolic pathways. Given the intricate relationship between cancer metabolism and the immune system, the metabolic defects imposed by serine deprivation might impact tumor-targeting immunity. In this study, we demonstrated that restricting endogenous and exogenous sources of serine in colorectal cancer cells results in mitochondrial dysfunction, leading to mitochondrial DNA (mtDNA) accumulation in the cytosol and consequent cGAS-STING1-driven type I IFN secretion. Depleting mtDNA or blocking its release attenuated cGAS-STING1 activation during serine deprivation. In vivo studies revealed that serine deprivation limits tumor growth, accompanied by enhanced type I IFN signaling and intratumoral infiltration of immune effector cells. Notably, the tumor-suppressive and immune-enhancing effects of serine restriction were impaired by T-cell depletion and IFN receptor blockade. Moreover, disrupting cGAS-STING1 signaling in colorectal cancer cells limited the immunostimulatory and tumor-suppressive effects of serine deprivation. Lastly, serine depletion increased the sensitivity of tumors to an immune checkpoint inhibitor targeting PD-1. Taken together, these findings reveal a role for serine as a suppressor of antitumor immunity, suggesting that serine deprivation may be employed to enhance tumor immunogenicity and improve responsiveness to immune checkpoint inhibitors.

Significance: Depriving cancer cells of serine provokes mitochondrial perturbations that induce cytosolic mitochondrial DNA accumulation and subsequent activation of cGAS-STING signaling, stimulating tumor-targeting immune responses that can be enhanced with PD-1 targeted therapy.

See related commentary by Borges and Garg, p. 2569
Data from Increased Protein Kinase A Activity Induces Fibrolamellar Hepatocellular Carcinoma Features Independent of DNAJB1
Authors: Shirani Mahsa , Levin Solomon , Shebl Bassem , Requena David , Finkelstein Tova M. , Johnson Daniel S. , Ng Denise , Lalazar Gadi , Heissel Søren , Hojrup Peter , Molina Henrik , de Jong Ype P. , Rice Charles M. , Singhi Aatur D. , Torbenson Michael S. , Coffino Philip , Lyons Barbara , Simon Sanford M.
Published: August 2024

Abstract
Fibrolamellar hepatocellular carcinoma (FLC) is a rare liver cancer that is driven by the fusion of DNAJB1 and PRKACA, the catalytic subunit of protein kinase A (PKA). PKA activity is controlled through regulatory proteins that both inhibit catalytic activity and control localization, and an excess of regulatory subunits ensures PRKACA activity is inhibited. Here, we found an increase in the ratio of catalytic to regulatory units in FLC patient tumors driven by DNAJB1::PRKACA using mass spectrometry, biochemistry, and immunofluorescence, with increased nuclear localization of the kinase. Overexpression of DNAJB1::PRKACA, ATP1B1::PRKACA, or PRKACA, but not catalytically inactive kinase, caused similar transcriptomic changes in primary human hepatocytes, recapitulating the changes observed in FLC. Consistently, tumors in patients missing a regulatory subunit or harboring an ATP1B1::PRKACA fusion were indistinguishable from FLC based on the histopathological, transcriptomic, and drug–response profiles. Together, these findings indicate that the DNAJB1 domain of DNAJB1::PRKACA is not required for FLC. Instead, changes in PKA activity and localization determine the FLC phenotype.

Significance: Alterations leading to unconstrained protein kinase A signaling, regardless of the presence or absence of PRKACA fusions, drive the phenotypes of fibrolamellar hepatocellular carcinoma, reshaping understanding of the pathogenesis of this rare liver cancer.
Data from The DRAP1/DR1 Repressor Complex Increases mTOR Activity to Promote Progression and Confer Everolimus Sensitivity in Triple-Negative Breast Cancer
Authors: Huang Min-Ying , Hu Shu-Yuan , Dong Jia , Deng Ling , Andriani Lisa , Ma Xiao-Yan , Zhang Yin-Ling , Zhang Fang-Lin , Shao Zhi-Ming , Li Da-Qiang
Published: August 2024

Abstract
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Transcriptional dysregulation is a hallmark of cancer, and several transcriptional regulators have been demonstrated to contribute to cancer progression. In this study, we identified an upregulation of the transcriptional corepressor downregulator of transcription 1–associated protein 1 (DRAP1) in TNBC, which was closely associated with poor recurrence-free survival in patients with TNBC. DRAP1 promoted TNBC proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. Mechanistically, the downregulator of transcription 1 (DR1)/DRAP1 heterodimer complex inhibited expression of the cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1) and thereby increased activation of mTOR, which sensitized TNBC to treatment with the mTOR inhibitor everolimus. DRAP1 and DR1 also formed a positive feedback loop. DRAP1 enhanced the stability of DR1 by recruiting the deubiquitinase USP7 to inhibit its proteasomal degradation; in turn, DR1 directly promoted DRAP1 transcription. Collectively, this study uncovered a DRAP1–DR1 bidirectional regulatory pathway that promotes TNBC progression, suggesting that targeting the DRAP1/DR1 complex might be a potential therapeutic strategy to treat TNBC.

Significance: DR1 and DRAP1 form a positive feedback loop and a repressor complex to cooperatively inhibit cytosolic arginine sensor for mTORC1 subunit 1 transcription and stimulate mTOR signaling, leading to progression and increased everolimus sensitivity in triple-negative breast cancer.
Supplementary Table S2 from Urinary Metabolite Diagnostic and Prognostic Liquid Biopsy Biomarkers of Lung Cancer in Nonsmokers and Tobacco Smokers
Authors: Dalal Bhavik , Tada Takeshi , Patel Daxesh P. , Pine Sharon R. , Khan Mohammed , Oike Takahiro , Kanke Yasuyuki , Parker Amelia L. , Haznadar Majda , Toulabi Leila , Krausz Kristopher W. , Robles Ana I. , Bowman Elise D. , Gonzalez Frank J. , Harris Curtis C.
Published: August 2024

Univariate and multivariate regression analysis for clinical factors, metabolite levels and prognosis in smokers.
Supplementary Table S4 from A Novel Approach to Quantify Heterogeneity of Intrahepatic Cholangiocarcinoma: The Hidden-Genome Classifier
Authors: Song Yi , Boerner Thomas , Drill Esther , Shin Paul , Kumar Sandeep , Sigel Carlie , Cercek Andrea , Kemeny Nancy , Abou-Alfa Ghassan , Iacobuzio-Donahue Christine , Cowzer Darren , Schultz Nikolaus , Walch Henry , Balachandran Vinod , Groot Koerkamp Bas , Kingham Peter , Soares Kevin , Wei Alice , D’Angelica Michael , Drebin Jeffrey , Chandwani Rohit , Harding James J. , Jarnagin William
Published: August 2024

This table reports the lasso-selected active genetic predictors of the hidden-genome model. The predictive power is represented by the GBC/EHC odds ratio (OR) or HCC OR. The max OR is the greater of the two values. The Shannon-Jensen importance is represented by the average individual effect and the max individual effect. FGFR2 fusion and BAP1 mutation were not identified by the algorithm as lasso-selected active genetic predictors and had very low Shannon-Jensen importance. Therefore, FGFR2 fusion and BAP1 mutation were not included in the table.
Figure 2 from Urinary Metabolite Diagnostic and Prognostic Liquid Biopsy Biomarkers of Lung Cancer in Nonsmokers and Tobacco Smokers
Authors: Dalal Bhavik , Tada Takeshi , Patel Daxesh P. , Pine Sharon R. , Khan Mohammed , Oike Takahiro , Kanke Yasuyuki , Parker Amelia L. , Haznadar Majda , Toulabi Leila , Krausz Kristopher W. , Robles Ana I. , Bowman Elise D. , Gonzalez Frank J. , Harris Curtis C.
Published: August 2024

Distribution of CR and NANA metabolite levels in former and current smoker cases. Violin plots were used to depict the summary statistics and the density of each variable in different groups within the (A) exploratory cohort and (B) validation cohort. ****P < 0.0001; ***P < 0.001; **P < 0.01; ns, not significant; x͂ = median.
Supplementary Table S4 from Tissue-Free Liquid Biopsies Combining Genomic and Methylation Signals for Minimal Residual Disease Detection in Patients with Early Colorectal Cancer from the UK TRACC Part B Study
Authors: Slater Susanna , Bryant Annette , Aresu Maria , Begum Ruwaida , Chen Hsiang-Chi , Peckitt Clare , Lazaro-Alcausi Retchel , Carter Paul , Anandappa Gayathri , Khakoo Shelize , Melcher Lucinda , Potter Vanessa , Marti Francisca M. , Huang Joesph , Branagan Graham , George Nicol , Abulafi Muti , Duff Sarah , Raja Ashraf , Gupta Ashish , West Nicholas , Bucheit Leslie , Rich Thereasa , Chau Ian , Cunningham David , Starling Naureen
Published: August 2024

Results of the primary, landmark, and longitudinal analysis populations
Supplementary Table S2 from Tissue-Free Liquid Biopsies Combining Genomic and Methylation Signals for Minimal Residual Disease Detection in Patients with Early Colorectal Cancer from the UK TRACC Part B Study
Authors: Slater Susanna , Bryant Annette , Aresu Maria , Begum Ruwaida , Chen Hsiang-Chi , Peckitt Clare , Lazaro-Alcausi Retchel , Carter Paul , Anandappa Gayathri , Khakoo Shelize , Melcher Lucinda , Potter Vanessa , Marti Francisca M. , Huang Joesph , Branagan Graham , George Nicol , Abulafi Muti , Duff Sarah , Raja Ashraf , Gupta Ashish , West Nicholas , Bucheit Leslie , Rich Thereasa , Chau Ian , Cunningham David , Starling Naureen
Published: August 2024

Baseline and postoperative characteristics by longitudinal ctDNA status in patients still in follow-up (no recurrence) in the longitudinal analysis population (n=126)
Supplementary Table S6 from Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma
Authors: Saner Flurina A.M. , Takahashi Kazuaki , Budden Timothy , Pandey Ahwan , Ariyaratne Dinuka , Zwimpfer Tibor A. , Meagher Nicola S. , Fereday Sian , Twomey Laura , Pishas Kathleen I. , Hoang Therese , Bolithon Adelyn , Traficante Nadia , Alsop Kathryn , Christie Elizabeth L. , Kang Eun-Young , Nelson Gregg S. , Ghatage Prafull , Lee Cheng-Han , Riggan Marjorie J. , Alsop Jennifer , Beckmann Matthias W. , Boros Jessica , Brand Alison H. , Brooks-Wilson Angela , Carney Michael E. , Coulson Penny , Courtney-Brooks Madeleine , Cushing-Haugen Kara L. , Cybulski Cezary , El-Bahrawy Mona A. , Elishaev Esther , Erber Ramona , Gayther Simon A. , Gentry-Maharaj Aleksandra , Gilks C. Blake , Harnett Paul R. , Harris Holly R. , Hartmann Arndt , Hein Alexander , Hendley Joy , Hernandez Brenda Y. , Jakubowska Anna , Jimenez-Linan Mercedes , Jones Michael E. , Kaufmann Scott H. , Kennedy Catherine J. , Kluz Tomasz , Koziak Jennifer M. , Kristjansdottir Björg , Le Nhu D. , Lener Marcin , Lester Jenny , Lubiński Jan , Mateoiu Constantina , Orsulic Sandra , Ruebner Matthias , Schoemaker Minouk J. , Shah Mitul , Sharma Raghwa , Sherman Mark E. , Shvetsov Yurii B. , Soong T. Rinda , Steed Helen , Sukumvanich Paniti , Talhouk Aline , Taylor Sarah E. , Vierkant Robert A. , Wang Chen , Widschwendter Martin , Wilkens Lynne R. , Winham Stacey J. , Anglesio Michael S. , Berchuck Andrew , Brenton James D. , Campbell Ian , Cook Linda S. , Doherty Jennifer A. , Fasching Peter A. , Fortner Renée T. , Goodman Marc T. , Gronwald Jacek , Huntsman David G. , Karlan Beth Y. , Kelemen Linda E. , Menon Usha , Modugno Francesmary , Pharoah Paul D.P. , Schildkraut Joellen M. , Sundfeldt Karin , Swerdlow Anthony J. , Goode Ellen L. , DeFazio Anna , Köbel Martin , Ramus Susan J. , Bowtell David D.L. , Garsed Dale W.
Published: August 2024

Supplementary Table S6. Summary of gene alterations in cell lines.
Supplementary Table S13 from Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma
Authors: Saner Flurina A.M. , Takahashi Kazuaki , Budden Timothy , Pandey Ahwan , Ariyaratne Dinuka , Zwimpfer Tibor A. , Meagher Nicola S. , Fereday Sian , Twomey Laura , Pishas Kathleen I. , Hoang Therese , Bolithon Adelyn , Traficante Nadia , Alsop Kathryn , Christie Elizabeth L. , Kang Eun-Young , Nelson Gregg S. , Ghatage Prafull , Lee Cheng-Han , Riggan Marjorie J. , Alsop Jennifer , Beckmann Matthias W. , Boros Jessica , Brand Alison H. , Brooks-Wilson Angela , Carney Michael E. , Coulson Penny , Courtney-Brooks Madeleine , Cushing-Haugen Kara L. , Cybulski Cezary , El-Bahrawy Mona A. , Elishaev Esther , Erber Ramona , Gayther Simon A. , Gentry-Maharaj Aleksandra , Gilks C. Blake , Harnett Paul R. , Harris Holly R. , Hartmann Arndt , Hein Alexander , Hendley Joy , Hernandez Brenda Y. , Jakubowska Anna , Jimenez-Linan Mercedes , Jones Michael E. , Kaufmann Scott H. , Kennedy Catherine J. , Kluz Tomasz , Koziak Jennifer M. , Kristjansdottir Björg , Le Nhu D. , Lener Marcin , Lester Jenny , Lubiński Jan , Mateoiu Constantina , Orsulic Sandra , Ruebner Matthias , Schoemaker Minouk J. , Shah Mitul , Sharma Raghwa , Sherman Mark E. , Shvetsov Yurii B. , Soong T. Rinda , Steed Helen , Sukumvanich Paniti , Talhouk Aline , Taylor Sarah E. , Vierkant Robert A. , Wang Chen , Widschwendter Martin , Wilkens Lynne R. , Winham Stacey J. , Anglesio Michael S. , Berchuck Andrew , Brenton James D. , Campbell Ian , Cook Linda S. , Doherty Jennifer A. , Fasching Peter A. , Fortner Renée T. , Goodman Marc T. , Gronwald Jacek , Huntsman David G. , Karlan Beth Y. , Kelemen Linda E. , Menon Usha , Modugno Francesmary , Pharoah Paul D.P. , Schildkraut Joellen M. , Sundfeldt Karin , Swerdlow Anthony J. , Goode Ellen L. , DeFazio Anna , Köbel Martin , Ramus Susan J. , Bowtell David D.L. , Garsed Dale W.
Published: August 2024

Supplementary Table S13. Clinical and molecular characteristics of ENOC.
Supplementary Table S12 from Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma
Authors: Saner Flurina A.M. , Takahashi Kazuaki , Budden Timothy , Pandey Ahwan , Ariyaratne Dinuka , Zwimpfer Tibor A. , Meagher Nicola S. , Fereday Sian , Twomey Laura , Pishas Kathleen I. , Hoang Therese , Bolithon Adelyn , Traficante Nadia , Alsop Kathryn , Christie Elizabeth L. , Kang Eun-Young , Nelson Gregg S. , Ghatage Prafull , Lee Cheng-Han , Riggan Marjorie J. , Alsop Jennifer , Beckmann Matthias W. , Boros Jessica , Brand Alison H. , Brooks-Wilson Angela , Carney Michael E. , Coulson Penny , Courtney-Brooks Madeleine , Cushing-Haugen Kara L. , Cybulski Cezary , El-Bahrawy Mona A. , Elishaev Esther , Erber Ramona , Gayther Simon A. , Gentry-Maharaj Aleksandra , Gilks C. Blake , Harnett Paul R. , Harris Holly R. , Hartmann Arndt , Hein Alexander , Hendley Joy , Hernandez Brenda Y. , Jakubowska Anna , Jimenez-Linan Mercedes , Jones Michael E. , Kaufmann Scott H. , Kennedy Catherine J. , Kluz Tomasz , Koziak Jennifer M. , Kristjansdottir Björg , Le Nhu D. , Lener Marcin , Lester Jenny , Lubiński Jan , Mateoiu Constantina , Orsulic Sandra , Ruebner Matthias , Schoemaker Minouk J. , Shah Mitul , Sharma Raghwa , Sherman Mark E. , Shvetsov Yurii B. , Soong T. Rinda , Steed Helen , Sukumvanich Paniti , Talhouk Aline , Taylor Sarah E. , Vierkant Robert A. , Wang Chen , Widschwendter Martin , Wilkens Lynne R. , Winham Stacey J. , Anglesio Michael S. , Berchuck Andrew , Brenton James D. , Campbell Ian , Cook Linda S. , Doherty Jennifer A. , Fasching Peter A. , Fortner Renée T. , Goodman Marc T. , Gronwald Jacek , Huntsman David G. , Karlan Beth Y. , Kelemen Linda E. , Menon Usha , Modugno Francesmary , Pharoah Paul D.P. , Schildkraut Joellen M. , Sundfeldt Karin , Swerdlow Anthony J. , Goode Ellen L. , DeFazio Anna , Köbel Martin , Ramus Susan J. , Bowtell David D.L. , Garsed Dale W.
Published: August 2024

Supplementary Table S12. Clinical characteristics of patients with HGSC.