bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a fully automated chemiluminescent immunoassay for the quantitative and qualitative detection of antibodies against African swine fever virus p72
Authors: Wang Lei , Li Duan , Zeng Daoping , Wang Shuangyun , Wu Jianwen , Liu Yanlin , Peng Guoliang , Xu Zheng , Jia Hong , Song Changxu
Published: August 2024

African swine fever (ASF), caused by ASF virus (ASFV), is a highly infectious and severe hemorrhagic disease of pigs that causes major economic losses. Currently, no commercial vaccine is available and prevention and control of ASF relies mainly on early diagnosis. Here, a novel automated double antigen sandwich chemiluminescent immunoassay (DAgS-aCLIA) was developed to detect antibodies against ASFV p72 (p72-Ab). For this purpose, recombinant p72 trimer was produced, coupled to magnetic particles as carriers and labeled with acridinium ester as a signal trace. Finally, p72-Ab can be sensitively and rapidly measured on an automated chemiluminescent instrument. For quantitative analysis, a calibration curve was established with a laudable linearity range of 0.21 to 212.0 ng/mL (R
2
= 0.9910) and a lower detection limit of 0.15 ng/mL. For qualitative analysis, a cut-off value was set at 1.50 ng/mL with a diagnostic sensitivity of 100.00% and specificity of 98.33%. Furthermore, antibody response to an ASF gene-deleted vaccine candidate can be accurately quantified using this DAgS-aCLIA, as evidenced by early seroconversion as early as 7 days post-immunization and high antibody levels. Compared with available enzyme-linked immunosorbent assays, this DAgS-aCLIA demonstrated a wider linearity range of 4 to 16-fold, and excellent analytical sensitivity and agreement of over 95.60%. In conclusion, our proposed DAgS-aCLIA would be an effective tool to support ASF epidemiological surveillance.

IMPORTANCE

African swine fever virus (ASFV) is highly contagious in wild boar and domestic pigs. There is currently no vaccine available for ASF, so serological testing is an important diagnostic tool. Traditional enzyme-linked immunosorbent assays provide only qualitative results and are time and resource consuming. This study will develop an automated chemiluminescent immunoassay (CLIA) that can quantitatively and qualitatively detect antibodies to ASFV p72, greatly reducing detection time and labour-intensive operation, and improving detection sensitivity and linearity range. This novel CLIA would serve as a reliable and convenient tool for ASF pandemic surveillance and vaccine development.
Dynamic Magnetic Susceptibility Method in Studies of Coordination Compounds
Authors: Efimov N. N. , Babeshkin K. A. , Rotov A. V.
Published: August 2024

The measurement of the dynamic magnetic susceptibility is a universal method, which is used for the evaluation of magnetic properties of single molecule magnets by scientists all over the world. An information in the Russian scientific literature that can be useful for practical mastering of this method is presently insufficient. To fill this gap, in this work we present a detailed procedure of a magnetochemical experiment for observing slow magnetic relaxation in coordination compounds of 3d- and 4f-element ions and the complete characterization of the dynamics of the magnetic behavior. Special attention is given to usually omitted but important details related to all stages of studying the magnetic relaxation dynamics. The main variants of sample preparation are described, the logics of the construction of a measuring sequence and the procedure of experimental data processing are discussed, and advantages and drawbacks of some programs of the calculation of magnetic relaxation dynamics data are considered. The main concepts and equations used in experimental data analysis are presented, and the primary conclusions that can be made from the obtained results are proposed.
As bleak as it sounds? Analysing trends in oncology clinical trial initiation in the UK from 2010 to 2022
Authors: VanHelene Alexander David , Hadfield Matthew J , Trapani Dario , Warner Jeremy Lyle , Lythgoe Mark P
Published: August 2024

Objectives

The UK’s withdrawal from the European Union (a political movement known as ‘Brexit’) incited concern both in the public and private sector about the future of drug development and the clinical trial landscape in the UK. This study evaluates trends in the initiation of phase III clinical trials that evaluated systemic anticancer treatments from 2010 to 2022 both in the UK and worldwide.

Methods and analysis

Relevant clinical trials were identified through ClinicalTrials.gov. Initiation date in each country was defined as the date that a study’s record was updated to include a recruiting site in the country of interest. Concurrent clinical site counts were defined as the number of facilities that contemporaneously hosted trials. Temporal trends in trial initiation and site counts were evaluated.

Results

Our analysis uncovered a worldwide increase in clinical trial initiation from 2013 to 2019. The UK experienced a decrease in clinical trial initiation immediately post-Brexit in 2020 but rebounded in 2021. The UK’s resurgence in clinical trials in 2021 was driven predominately by industry-funded trials. Other countries saw a similar increase in clinical trial initiation from 2020 to 2021.

Conclusions

The UK’s trends in phase III oncology clinical trial initiation from 2010 to 2022 largely reflects global trends, suggesting that other factors (eg, COVID-19 pandemic) beyond Brexit, may have had a stronger influence on clinical trial initiation within the UK.
Diabetes self-management: a qualitative study of education needs, practices and caregiver support in the Keta Municipality of Ghana
Authors: Tetteh Cynthia , Saah Farrukh Ishaque , Amu Hubert
Published: August 2024

Introduction

A major part of diabetes management involves patients’ self-management. Poor self-management increases the risk of complications from the condition. Good self-management requires appropriate and adequate education and caregiver support, typically provided through structured diabetes education programmes. Education on various topics, including self-management, is a key component of diabetes management services in Ghana. However, challenges such as limited knowledge, economic constraints and sociocultural factors hinder self-management practices. We explored the self-management education (SME), practice and support needs of adults with type-2 diabetes (T2D) at the Keta Municipal Hospital.

Research design and methods

This phenomenological study involved 16 adults living with T2D and two healthcare providers in the Keta Municipality of Ghana. Data were collected through in-depth and expert interviews using interview guides. Interpretative phenomenological analysis was employed to analyse the data using NVivo V.12.

Results

SME was provided within an hour during the first section of the monthly diabetes clinic covering dietary needs and restrictions, physical exercises, adherence to medication and wound prevention and care. SME needs were individualised SME and extension of education to the general population. The participants practised self-management activities. They attributed their improved practices to both the general group education and the individualised goals and input received during individual counselling sessions. Motivators for self-management were cues from negative health outcomes, wanting to survive the condition for a long time and SME received. Challenges to self-management entailed job roles, insufficient medication dosages and unavailability of medication at the hospital during review visits.

Conclusions

The study suggests that individualised SME and caregiver support may enhance self-management practices and outcomes. This underscores the significance of considering patient-specific factors and support systems when designing effective diabetes management strategies. The provision of comprehensive SME, including group and individual sessions, along with the utilisation of visual aids, can contribute to improved self-management outcomes.
Psychotherapy use among migrants: a register-based longitudinal study
Authors: Lehti Venla , Kieseppä Valentina , Gissler Mika , Suvisaari Jaana , Markkula Niina
Published: August 2024

Background

Migrants use less mental health services compared with non-migrant populations, but there is very little information on the use of long-term psychotherapy among migrants. Finnish register data allow for studying the whole migrant population in Finland and collecting data on all publicly supported rehabilitative psychotherapy.

Methods

This study is based on a sample of migrants (n=185 605) and Finnish-born controls (n=185 605). Participants who had received reimbursements for rehabilitative psychotherapy during 2007–2020 were identified from a register maintained by the Social Insurance Institution of Finland. Cox regression analysis was used to study the effect of migrant status on the time until the start of therapy. Multinomial logistic regression was used to study the association between migrant status and the number of psychotherapy sessions.

Results

Finnish-born participants received psychotherapy more often (n=7258) than migrants (n=1516). The adjusted HR for initiating psychotherapy among migrants compared with Finnish-born individuals was 0.27 (95% CI 0.25 to 0.28). Migrants from sub-Saharan Africa and Asia and recently arrived migrants were least likely to receive psychotherapy. Migrants were more likely to receive short treatment periods than Finnish-born controls.

Conclusion

Lower use of rehabilitative psychotherapy among migrant population in Finland is not likely to reflect lower need for treatment. More efforts are needed to promote equal access to psychotherapy.
Double-Ended Bit-Stealing for Algebraic Data Types
Authors: Elsman Martin
Published: August 2024

Algebraic data types are central to the development and evaluation of most functional programs. It is therefore important for compilers to choose compact and efficient representations of such types, in particular to achieve good memory footprints for applications.

Algebraic data types are most often represented using blocks of memory where the first word is used as a so-called tag, carrying information about the constructor, and the following words are used for carrying the constructor's arguments. As an optimisation, lists are usually represented more compactly, using a technique called bit-stealing, which, in its simplest form, uses the word-alignment property of pointers to byte-addressed allocated memory to discriminate between the nil constructor (often represented as 0x1) and the cons constructor (aligned pointer to allocated pair). Because the representation supports that all values can be held uniformly in one machine word, possibly pointing to blocks of memory, type erasure is upheld.

However, on today's 64-bit architectures, memory addresses (pointers) are represented using only a subset of the 64 bits available in a machine word, which leave many bits unused. In this paper, we explore the use, not only of the least-significant bits of pointers, but also of the most-significant bits, for representing algebraic data types in a full ML compiler. It turns out that, with such a particular utilisation of otherwise unused bits, which we call double-ended bit-stealing, it is possible to choose unboxed representations for a large set of data types, while still not violating the principle of uniform data-representations. Examples include Patricia trees, union-find data structures, stream data types, internal language representations for types and expressions, and mutually recursive ASTs for full language definitions.

The double-ended bit-stealing technique is implemented in the MLKit compiler and speedup ranges from 0 to 26 percent on benchmarks that are influenced by the technique. For MLKit, which uses abstract data types extensively, compilation speedups of around 9 percent are achieved for compiling MLton (another Standard ML compiler) and for compiling MLKit itself.
The Long Way to Deforestation: A Type Inference and Elaboration Technique for Removing Intermediate Data Structures
Authors: Chen Yijia , Parreaux Lionel
Published: August 2024

Deforestation is a compiler optimization that removes intermediate data structure allocations from functional programs to improve their efficiency. This is an old idea, but previous approaches have proved limited or impractical — they either only worked on compositions of predefined combinators (shortcut fusion), or involved the aggressive unfolding of recursive definitions until a depth limit was reached or a reoccurring pattern was found to tie the recursive knot, resulting in impractical algorithmic complexity and large amounts of code duplication. We present Lumberhack, a general-purpose deforestation approach for purely functional call-by-value programs. Lumberhack uses subtype inference to reason about data structure production and consumption and uses an elaboration pass to fuse the corresponding recursive definitions. It fuses large classes of mutually recursive definitions while avoiding much of the unproductive (and sometimes counter-productive) code duplication inherent in previous approaches. We prove the soundness of Lumberhack using logical relations and experimentally demonstrate significant speedups in the standard nofib benchmark suite. We manually adapted nofib programs to call-by-value semantics and compiled them using the OCaml compiler. The average speedup over the 38 benchmarked programs is 8.2% while the average code size increases by just about 1.79x. In particular, 19 programs see their performance mostly unchanged, 17 programs improve significantly (by an average speedup of 16.6%), and only three programs visibly worsen (by an average slowdown of 1.8%). As a point of comparison, we measured that the well-proven but semi-manual list fusion technique of the Glasgow Haskell Compiler (GHC), which only works for call-by-need programs, had an average speedup of 6.5%. Our technique is in its infancy still and misses many deforestation opportunities. We are confident that further refinements to the core technique will yield greater performance improvements in the future.
Grokking the Sequent Calculus (Functional Pearl)
Authors: Binder David , Tzschentke Marco , Müller Marius , Ostermann Klaus
Published: August 2024

The sequent calculus is a proof system which was designed as a more symmetric alternative to natural deduction. The 𝜆𝜇𝜇-calculus is a term assignment system for the sequent calculus and a great foundation for compiler intermediate languages due to its first-class representation of evaluation contexts. Unfortunately, only experts of the sequent calculus can appreciate its beauty. To remedy this, we present the first introduction to the 𝜆𝜇𝜇-calculus which is not directed at type theorists or logicians but at compiler hackers and programming-language enthusiasts. We do this by writing a compiler from a small but interesting surface language to the 𝜆𝜇𝜇-calculus as a compiler intermediate language.
Sound Borrow-Checking for Rust via Symbolic Semantics
Authors: Ho Son , Fromherz Aymeric , Protzenko Jonathan
Published: August 2024

The Rust programming language continues to rise in popularity, and as such, warrants the close attention of the programming languages community. In this work, we present a new foundational contribution towards the theoretical understanding of Rust’s semantics. We prove that LLBC, a high-level, borrow-centric model previously proposed for Rust’s semantics and execution, is sound with regards to a low-level pointer-based language
à la
CompCert. Specifically, we prove the following: that LLBC is a correct view over a traditional model of execution; that LLBC’s symbolic semantics are a correct abstraction of LLBC programs; and that LLBC’s symbolic semantics act as a borrow-checker for LLBC, i.e. that symbolically-checked LLBC programs do not get stuck when executed on a heap-and-addresses model of execution. To prove these results, we introduce a new proof style that considerably simplifies our proofs of simulation, which relies on a notion of hybrid states. Equipped with this reasoning framework, we show that a new addition to LLBC’s symbolic semantics, namely a join operation, preserves the abstraction and borrow-checking properties. This in turn allows us to add support for loops to the Aeneas framework; we show, using a series of examples and case studies, that this unlocks new expressive power for Aeneas.
Gradual Indexed Inductive Types
Authors: Malewski Mara , Maillard Kenji , Tabareau Nicolas , Tanter Éric
Published: August 2024

Indexed inductive types are essential in dependently-typed programming languages, enabling precise and expressive specifications of data structures and properties. Recognizing that programming and proving with dependent types could benefit from the smooth integration of static and dynamic checking that gradual typing offers, recent efforts have studied gradual dependent types. Gradualizing indexed inductive types however remains mostly unexplored: the standard encodings of indexed inductive types in intensional type theory, e.g., using type-level fixpoints or subset types, break in the presence of gradual features; and previous work on gradual dependent types focus on very specific instances of indexed inductive types. This paper contributes a general framework, named PUNK, specifically designed for exploring the design space of gradual indexed inductive types. PUNK is a versatile framework, enabling the exploration of the space between eager and lazy cast reduction semantics that arise from the interaction between casts and the inductive eliminator, allowing them to coexist and interoperate in a single system. Our work provides significant insights into the intersection of dependent types and gradual typing, by proposing a criteria for well-behaved gradual indexed inductive types, systematically addressing the outlined challenges of integrating these types. The contributions of this paper are a step forward in the quest for making gradual theorem proving and gradual dependently-typed programming a reality.
Specification and Verification for Unrestricted Algebraic Effects and Handling
Authors: Song Yahui , Foo Darius , Chin Wei-Ngan
Published: August 2024

Programming with user-defined effects and effect handlers has many practical use cases involving imperative effects. Additionally, it is natural and powerful to use multi-shot effect handlers for non-deterministic or probabilistic programs that allow backtracking to compute a comprehensive outcome. Existing works for verifying effect handlers are restricted in one of three ways: i) permitting multi-shot continuations under pure setting; ii) allowing heap manipulation for only one-shot continuations; or iii) allowing multi-shot continuations with heap-manipulation but under a restricted frame rule.

This work proposes a novel calculus called Effectful Specification Logic (ESL) to support unrestricted effect handlers, where zero-/one-/multi-shot continuations can co-exist with imperative effects and higher-order constructs. ESL captures behaviors in stages, and provides precise models to support invoked effects, handlers and continuations. To show its feasibility, we prototype an automated verification system for this novel specification logic, prove its soundness, report on useful case studies, and present experimental results. With this proposal, we have provided an extended specification logic that is capable of modeling arbitrary imperative higher-order programs with algebraic effects and continuation-enabled handlers.
Synchronous Programming with Refinement Types
Authors: Chen Jiawei , de Mendonça José Luiz Vargas , Ayele Bereket Shimels , Bekele Bereket Ngussie , Jalili Shayan , Sharma Pranjal , Wohlfeil Nicholas , Zhang Yicheng , Jeannin Jean-Baptiste
Published: August 2024

Cyber-Physical Systems (CPS) consist of software interacting with the physical world, such as robots, vehicles, and industrial processes. CPS are frequently responsible for the safety of lives, property, or the environment, and so software correctness must be determined with a high degree of certainty. To that end, simply testing a CPS is insufficient, as its interactions with the physical world may be difficult to predict, and unsafe conditions may not be immediately obvious. Formal verification can provide stronger safety guarantees but relies on the accuracy of the verified system in representing the real system. Bringing together verification and implementation can be challenging, as languages that are typically used to implement CPS are not easy to formally verify, and languages that lend themselves well to verification often abstract away low-level implementation details. Translation between verification and implementation languages is possible, but requires additional assurances in the translation process and increases software complexity; having both in a single language is desirable. This paper presents a formalization of MARVeLus, a CPS language which combines verification and implementation. We develop a metatheory for its synchronous refinement type system and demonstrate verified synchronous programs executing on real systems.
A Coq Mechanization of JavaScript Regular Expression Semantics
Authors: De Santo Noé , Barrière Aurèle , Pit-Claudel Clément
Published: August 2024

We present an executable, proven-safe, faithful, and future-proof Coq mechanization of JavaScript regular expression (regex) matching, as specified by the latest published edition of ECMA-262 section 22.2. This is, to our knowledge, the first time that an industrial-strength regex language has been faithfully mechanized in an interactive theorem prover. We highlight interesting challenges that arose in the process (including issues of encoding, corner cases, and executability), and we document the steps that we took to ensure that the result is straightforwardly auditable and that our understanding of the specification aligns with existing implementations.

We demonstrate the usability and versatility of the mechanization through a broad collection of analyses, case studies, and experiments: we prove that JavaScript regex matching always terminates and is safe (no assertion failures); we identify subtle corner cases that led to mistakes in previous publications; we verify an optimization extracted from a state-of-the-art regex engine; we show that some classic properties described in automata textbooks and used in derivatives-based matchers do not hold in JavaScript regexes; and we demonstrate that the cost of updating the mechanization to account for changes in the original specification is reasonably low.

Our mechanization can be extracted to OCaml and JavaScript and linked with Unicode libraries to produce an executable regex engine that passes the relevant parts of the official Test262 conformance test suite.
Carbon Rebellion: Empowerment Using Data-Driven Narratives
Authors: Shahu Ambika , Wölfer Martin , Michahelles Florian
Published: August 2024

Climate change communication demands narratives that resonate widely. “Carbon Rebellion,” an Interactive Digital Narrative, exemplifies this by blending personal anecdotes with data-driven content, fostering deep engagement. This research highlights the power of narratives in articulating the gravity of climate change, emphasizing the need for collective action and policy-level interventions. By juxtaposing individual choices against the backdrop of broader societal implications, the narrative seeks to both inspire and empower individuals. The findings reveal that such narratives can elicit strong emotional responses, catalyze critical thinking, and drive proactive climate action. The narrative’s emphasis on community-based efforts highlights the pivotal role of collective endeavors in addressing this global challenge.
Contingent Credit Under Stress
Authors: Acharya Viral V. , Jager Maximilian , Steffen Sascha
Published: August 2024

Over the past two decades, banks have increasingly focused on offering contingent credit in the form of credit lines as a primary means of corporate borrowing. We review the existing body of research regarding the rationales for banks’ provision of liquidity insurance in the form of credit lines, their significance in managing corporate liquidity, and the reasons and circumstances under which firms opt to utilize them. We emphasize that the options for firms to both draw down and repay credit lines are put options issued by banks, which are exercised by firms in a correlated manner during periods of widespread stress, with adverse effects on bank intermediation thereafter. We discuss the bank capital and the bank funding channels that can drive these effects, contrasting their roles during the global financial crisis of 2007–2008 and the COVID-19 outbreak. We conclude by discussing the increasing extension of bank credit lines to nonbank financial intermediaries as well as the role of stress tests and monetary policy in managing the risks of contingent credit under stress.
Androgen receptor markers do not differ between nonresponders and responders to resistance training-induced muscle hypertrophy
Authors: Bergamasco João G. A. , Scarpelli Maíra C. , Godwin Joshua S. , Mesquita Paulo H. C. , Chaves Talisson S. , da Silva Deivid G. , Bittencourt Diego , Dias Nathalia F. , Medalha Ricardo A. , Carello Filho Paulo C. , Angleri Vitor , Costa Luiz A. R. , Michel J. Max , Vechin Felipe C. , Kavazis Andreas N. , Ugrinowitsch Carlos , Roberts Michael D. , Libardi Cleiton A.
Published: August 2024

We explored, for the first time, the influence of androgen receptor (AR) through the separation of cytoplasmic and nuclear cell fractions [i.e., cytoplasmic androgen receptor (cAR), nuclear androgen receptor (nAR), and androgen receptor DNA-binding activity (AR-DNA)] on muscle hypertrophy responsiveness to resistance training. The absence of muscle hypertrophy in naïve individuals does not seem to be explained by baseline values, and acute or chronic changes in AR markers.
Supplementary Fig. S12 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. S12
Occupational Benzene Exposure and Cancer Risk among Chinese Men: A Report from the Shanghai Men’s Health Study
Authors: DeMoulin Douglas , Cai Hui , Vermeulen Roel , Zheng Wei , Lipworth Loren , Shu Xiao-Ou
Published: August 2024

Background:

Benzene exposure has been associated with increased risk of leukemia and other cancers; however, epidemiologic evidence is inconsistent for the latter, and confounding from smoking and alcohol was rarely adjusted.

Methods:

We investigated associations between occupational benzene exposure and risk of leukemia, lymphoma, myeloma, and lung, stomach, liver, and kidney cancers in a population-based cohort of 61,377 men, ages 40 to 74 years. A job-exposure matrix, constructed by industrial hygienists specifically for the study population, was used to derive cumulative benzene exposure from all jobs held. Cox regressions were performed to estimate adjusted HRs (aHR) and 95% confidence intervals (CI) for benzene–cancer risk associations with adjustment for potential confounders.

Results:

Over 15 years of follow-up, 1,145 lung cancer, 656 stomach cancer, 445 liver cancer, 243 kidney cancer, 100 leukemia, 124 lymphoma, and 46 myeloma cases were identified. Benzene exposure >550 mg/m3 was associated with an increased risk of leukemia (aHR = 2.3; 95% CI, 1.1–4.5), lung cancer (aHR = 1.2; 95% CI, 1.0–1.6), and stomach cancer (aHR = 1.4; 95% CI, 1.0–1.9); benzene exposure was associated with early cancer diagnosis age. The benzene–leukemia and benzene–stomach cancer associations followed a linear dose–response pattern (Plinear = 0.016 and 0.023), whereas the benzene–lung cancer association was evident at higher exposure levels (Pnonlinear = 0.027). Alcohol consumption modified the benzene–leukemia association (aHR = 3.0; 95% CI, 1.1–8.3 for drinkers and aHR = 0.9; 95% CI, 0.4–2.0 for nondrinkers, Pinteraction = 0.047).

Conclusions:

Benzene exposure was associated with an increased risk of leukemia, stomach cancer, and lung cancer. Alcohol consumption may modify the benzene–leukemia association, although estimates are imprecise.

Impact:

Our study provides additional evidence that benzene exposure increases cancer risk beyond leukemia, information important for policymakers to develop programs to mitigate cancer risk among benzene-exposed workers.
Supplementary Table S8 from A PDE3A-SLFN12 Molecular Glue Exhibits Significant Antitumor Activity in TKI-Resistant Gastrointestinal Stromal Tumors
Authors: Takaki Emiri O. , Kiyono Kunihiko , Obuchi Yutaka , Yamauchi Takeshi , Watanabe Takashi , Matsumoto Hideki , Karimine Miho , Kuniyoshi Yuki , Nishikori Shingo , Yokoyama Fumiharu , Nishimori Hikaru , Nabeshima Hiroshi , Nakamura Kazuhide
Published: August 2024

Supplementary Table 8. Knockdown efficiency of siRNAs in PFSK-1 cells
Supplementary Figure S7 from Missense Mutations in Myc Box I Influence Nucleocytoplasmic Transport to Promote Leukemogenesis
Authors: Arthur Nancy B.J. , Christensen Keegan A. , Mannino Kathleen , Ruzinova Marianna B. , Kumar Ashutosh , Gruszczynska Agata , Day Ryan B. , Erdmann-Gilmore Petra , Mi Yiling , Sprung Robert , York Conner R. , Townsend Robert R. , Spencer David H. , Sykes Stephen M. , Ferraro Francesca
Published: August 2024

Supplementary Figure 7. (A) UMAP projection of 36085 cells from MycT58N/+ and Myc+/+ mice colored by genotype, as indicated in the legend. (B) UMAP projection of 36085, split by genotype and colored by the combined expression of Mpo (Myeloperoxidase) and Elane (Elastase, Neutrophil Expressed) transcripts. In yellow are GMP cells, that strongly express both transcripts. (C) UMAP projection of 36085 cells split by genotype and colored by the combined expression of Cd177 and Ngp (neutrophil granule protein). In yellow are granulocytopoietic progenitors, that express high levels of both transcripts. (D) Trajectory analysis of 36085 showing the temporo-spatial expression of Myc (cells that express Myc are in shades of red). (E) Venn diagram showing the percentage overlap in scRNA-seq DEGs between the overexpression and the knockin mouse model. Comparisons are: Empty vector*GMP vs. MycT58N*GMP and MycT58N/+* GMP vs. Myc+/+*GMP for the overexpression and the knockin, respectively. 55% of the DEGs (8334 genes) are shared between the two models. (F) Schematic summary of the nucleocytoplasmic transport components’ transcripts that are upregulated >2 folds in MycT58N/+ versus Myc+/+(created with BioRender.com) (G) Enrichment plots (top) and heatmaps of the leading-edge genes in each pathway (bottom), showing the differential enrichment on Ribosome Biogenesis, Pyrimidine metabolism and Pluripotency pathways in MycT58N/+ GMP-like cells. (H) Enrichment plots (top) and heatmaps of the leading-edge genes in each pathway (bottom), showing the enrichment of Hematopoietic cell lineage and Immune pathways in Myc+/+ GMP-like cells.
Supplementary Table S5 from A PDE3A-SLFN12 Molecular Glue Exhibits Significant Antitumor Activity in TKI-Resistant Gastrointestinal Stromal Tumors
Authors: Takaki Emiri O. , Kiyono Kunihiko , Obuchi Yutaka , Yamauchi Takeshi , Watanabe Takashi , Matsumoto Hideki , Karimine Miho , Kuniyoshi Yuki , Nishikori Shingo , Yokoyama Fumiharu , Nishimori Hikaru , Nabeshima Hiroshi , Nakamura Kazuhide
Published: August 2024

Supplementary Table 5. Inhibition of cell viability by OPB-171775 in cancer cell lines.
Supplementary Figure S4 from Missense Mutations in Myc Box I Influence Nucleocytoplasmic Transport to Promote Leukemogenesis
Authors: Arthur Nancy B.J. , Christensen Keegan A. , Mannino Kathleen , Ruzinova Marianna B. , Kumar Ashutosh , Gruszczynska Agata , Day Ryan B. , Erdmann-Gilmore Petra , Mi Yiling , Sprung Robert , York Conner R. , Townsend Robert R. , Spencer David H. , Sykes Stephen M. , Ferraro Francesca
Published: August 2024

Supplementary Figure 4. (A) Histogram plot showing the viability (as measured by Acridine Orange/Propidium Iodine stain read on a Cellometer instrument) of control cells, MYCWT, MYCP59Q and MYCT58N expressing cells at before (time 0) and 8 hours after treatment with DRB. None of the difference are statistically significant. (B) Schematic overview of the nascent proteomic analysis experimental setup. (C) Volcano plots of the fold changes in spectral counts of MYC overexpressing (doxycycline treated) vs. control (vehicle treated) cells (Supplementary Data S7). Black dashed lines indicate significance (ANOVA, Dox vs Vehicle, fold changes ± 2, adjp<0.05) (D-E) Volcano plots showing the trends in spectral counts fold changes (x-axis) over 30 minutes of OPP nascent polypeptide labeling for cluster 3 genes (D) and for the genes in figure 4A (E). Comparisons are MBI MYCMUT*Dox vs MYCWT*Dox. Red dashed lines indicate significance.
Supplementary Table S10 from A PDE3A-SLFN12 Molecular Glue Exhibits Significant Antitumor Activity in TKI-Resistant Gastrointestinal Stromal Tumors
Authors: Takaki Emiri O. , Kiyono Kunihiko , Obuchi Yutaka , Yamauchi Takeshi , Watanabe Takashi , Matsumoto Hideki , Karimine Miho , Kuniyoshi Yuki , Nishikori Shingo , Yokoyama Fumiharu , Nishimori Hikaru , Nabeshima Hiroshi , Nakamura Kazuhide
Published: August 2024

Supplementary Table 10. List of genes positively selected by CRISPR‒Cas9 screening in the presence of 10 nM OPB-171775
Supplementary Data S7 from Missense Mutations in Myc Box I Influence Nucleocytoplasmic Transport to Promote Leukemogenesis
Authors: Arthur Nancy B.J. , Christensen Keegan A. , Mannino Kathleen , Ruzinova Marianna B. , Kumar Ashutosh , Gruszczynska Agata , Day Ryan B. , Erdmann-Gilmore Petra , Mi Yiling , Sprung Robert , York Conner R. , Townsend Robert R. , Spencer David H. , Sykes Stephen M. , Ferraro Francesca
Published: August 2024

Supplementary Data S7 Proteomic Normalized Spectral Counts
Supplementary Figure S4 from A PDE3A-SLFN12 Molecular Glue Exhibits Significant Antitumor Activity in TKI-Resistant Gastrointestinal Stromal Tumors
Authors: Takaki Emiri O. , Kiyono Kunihiko , Obuchi Yutaka , Yamauchi Takeshi , Watanabe Takashi , Matsumoto Hideki , Karimine Miho , Kuniyoshi Yuki , Nishikori Shingo , Yokoyama Fumiharu , Nishimori Hikaru , Nabeshima Hiroshi , Nakamura Kazuhide
Published: August 2024

Supplementary Fig. S4. GCN2 phosphorylation and downstream signaling induced by OPB-171775.
Supplementary Figure S3 from A PDE3A-SLFN12 Molecular Glue Exhibits Significant Antitumor Activity in TKI-Resistant Gastrointestinal Stromal Tumors
Authors: Takaki Emiri O. , Kiyono Kunihiko , Obuchi Yutaka , Yamauchi Takeshi , Watanabe Takashi , Matsumoto Hideki , Karimine Miho , Kuniyoshi Yuki , Nishikori Shingo , Yokoyama Fumiharu , Nishimori Hikaru , Nabeshima Hiroshi , Nakamura Kazuhide
Published: August 2024

Supplementary Fig. S3. Antagonistic effect of cilostamide on the anticancer activity of OPB-171775
Impact of Neoadjuvant Immunotherapy on Recurrence-Free Survival in Patients with High-Risk Localized HCC
Authors: Nakazawa Mari , Fang Mike , Vong Tyrus , Zorzi Jane , Griffith Paige , Anders Robert A. , Oshima Kiyoko , Kim Amy K. , Laurin Jacqueline , Lafaro Kelly J. , Shubert Christopher R. , Burns William R. , He Jin , Burkhart Richard A. , Philosophe Benjamin , Meyer Jeffrey , Liddell Robert P. , Georgiades Christos , Hong Kelvin , Ho Won Jin , Baretti Marina , Strauss Alexandra T. , Yarchoan Mark
Published: August 2024

Surgical resection for localized hepatocellular carcinoma (HCC) is typically reserved for a minority of patients with favorable tumor features and anatomy. Neoadjuvant immunotherapy can expand the number of patients who are candidates for surgical resection and potentially reduce the chance for recurrence, but its role in HCC not defined. We retrospectively examined the outcomes of patients who underwent surgical resection for HCC at the Johns Hopkins Hospital and compared the clinical outcomes of patients who received neoadjuvant immunotherapy with those who underwent upfront resection. The clinical cohort included a total of 92 patients, 36 of whom received neoadjuvant immune checkpoint inhibitor (ICI)-based treatment. A majority of patients (61.1%) who received neoadjuvant ICI–based therapy were outside of standard resectability criteria and were more likely to have features known to confer risk of disease recurrence, including α-fetoprotein ≥ 400 ng/mL (P = 0.02), tumor diameter ≥ 5 cm (P = 0.001), portal vein invasion (P < 0.001), and multifocality (P < 0.001). Patients who received neoadjuvant immunotherapy had similar rates of margin-negative resection (P = 0.47) and recurrence-free survival (RFS) as those who underwent upfront surgical resection (median RFS 44.8 months compared with 49.3 months, respectively, log-rank P = 0.66). There was a nonsignificant trend toward superior RFS in the subset of patients with a pathologic response (tumor necrosis ≥ 70%) with neoadjuvant immunotherapy. Neoadjuvant ICI-based therapy may allow high-risk patients, including those who are outside traditional resectability criteria, to achieve comparable clinical outcomes with those who undergo upfront resection.

Significance:

Surgical resection for localized HCC is typically only reserved for those with solitary tumors without vascular invasion. In this retrospective analysis, we show that neoadjuvant immunotherapy may allow high-risk patients, including those who are outside of standard resection criteria, to undergo successful margin-negative resection and achieve comparable long-term clinical outcomes compared with upfront resection. These findings highlight need for prospective studies on neoadjuvant immunotherapy in HCC.
Verhaltenstherapie einer intellektuell beeinträchtigten Patientin mit emotionaler Entwicklungsverzögerung, Depression und Verhaltensstörung
Authors: Kleischmann Annika , Scheytt Bettina , Willutzki Ulrike
Published: August 2024

Hintergrund: Menschen mit intellektueller Beeinträchtigung (IB) sind vulnerabel für psychische Störungen und Verhaltensstörungen. Der Zugang zur psychotherapeutischen Versorgung ist erschwert, u.a. aufgrund von Berührungsängsten der Behandler*innen und unberechtigten Zweifeln an der Wirksamkeit von Psychotherapie bei dieser Personengruppe. Durch Anpassung der Interventionen an die kognitiven Fähigkeiten und das emotionale Entwicklungsniveau ist Psychotherapie bei Menschen mit IB wirksam. Fallbericht: Zur Veranschaulichung einer entsprechenden Vorgehensweise wird die kognitive Verhaltenstherapie einer intellektuell beeinträchtigten Patientin mit emotionalen Entwicklungsverzögerungen, Depression und Verhaltensstörungen dargestellt. Nach Gewalterfahrungen in Kindheit und Jugend entwickelte sich selbstverletzendes Verhalten. Im Erwachsenenalter kamen depressive Symptome, mit ausgeprägter Selbstabwertung aufgrund der IB, hinzu. Schlussfolgerung: Durch Kombination psychotherapeutischer Techniken und Einbezug der Bezugsperson konnten das selbstverletzende Verhalten der Patientin deutlich reduziert werden sowie die depressiven Symptome remittieren. Die Auseinandersetzung mit der eigenen Beeinträchtigung führte zu gesteigerter Selbstakzeptanz. Es erwies sich als wesentlich, die kognitiven Fähigkeiten und vor allem das emotionale Entwicklungsniveau mit einzubeziehen.
Ambivalenzmodell der Suizidalität (ABS-Modell): Ein Verstehens- und Orientierungsmodell für die Behandlung suizidaler Personen
Authors: Teismann Tobias , Forkmann Thomas
Published: August 2024

Einleitung: Suizidales Erleben und Verhalten weist eine erhebliche Dynamik auf und ist sehr heterogen motiviert. Ein genaues Verständnis der individuellen Funktionsweise sui­zidalen Erlebens und Verhaltens stellt die Voraussetzung einer therapeutischen Aufarbeitung suizidaler Krisen dar. Methode: Ausgehend von der Feststellung, dass ambivalentes Erleben den gesamten suizidalen Prozess begleitet, wird im vorliegenden Artikel das Ambivalenzmodell der Suizidalität (ABS-Modell) als Verstehens- und Orientierungsmodell für die klinische Praxis vorgestellt. Ergebnisse: In dem Modell wird der suizidale Prozess in drei Phasen unterteilt (Unsicherheits-, Transitions- und Handlungsphase), es wird die psychische Befindlichkeit innerhalb der verschiedenen Phasen beschrieben und es werden phasenspezifische the­rapeutische Ansatzpunkte benannt. Diskussion/Schlussfolgerung: Beim ABS-Modell handelt es sich um ein deskriptives Modell, anhand dessen die Krisenintervention und Psychotherapie suizidaler Personen strukturiert und gestaltet werden kann.
ЗАСТОСУВАННЯ КАБІНИ ДЛЯ ПІДВІСНОЇ ТЕРАПІЇ ТА ЛІКУВАЛЬНОЇ ГІМНАСТИКИ ДЛЯ РЕАБІЛІТАЦІЇ ВІЙСЬКОВИХ ІЗ ВОГНЕПАЛЬНИМИ ПОРАНЕННЯМИ ПЛЕЧОВОГО СУГЛОБА
Authors: Ганчак Т. Ю. , Мисула І. Р.
Published: August 2024

РЕЗЮМЕ. Роль фізичного терапевта є ключовою в процесі лікування пацієнтів із вогнепальними пораненнями аби запобігти інвалідизації і зростає в геометричній прогресії від іммобілізаційного до відновного періоду. У процесі реабілітації важливе місце посідає вибір методів фізичної терапії. Ряд досліджень демонструє ефективність застосування кабіни для підвісної терапії, проте її роль у відновному періоді вивчена недостатньо.
Мета – розробити методику використання кабіни підвісної терапії для реабілітації пацієнтів з вогнепальними пораненнями плечового суглоба.
Матеріал і методи. На базі Тернопільської міської комунальної лікарні швидкої допомоги № 1 у стаціонарному відділенні реабілітації в період з травня по грудень 2023 року проведено лікування 30 поранених із вогнепальними ураженнями плечового суглоба. Пацієнтам впроваджена програма реабілітації з використанням елементів лікувальної гімнастики та кабіни для підвісної терапії.
Результати. Доведено, що стан пацієнтів, котрі займались за запропонованою програмою реабілітації з елементами лікувальної гімнастики та застосуванням кабіни для підвісної терапії, значно покращився. На це вказують показники ММТ, шкали ВАШ та гоніометрія.
Висновки. Застосування лікувальної гімнастики та кабіни для підвісної терапії є ефективними під час реабілітації пацієнтів із вогнепальними пораненнями плечового суглоба.
Принципи ортодонтичного лікування пацієнтів із вродженими однобічними незрощеннями верхньої губи та піднебіння: біомеханічне обґрунтування
Authors: Філоненко В. В.
Published: August 2024

Резюме. Лікування дітей із вродженими незрощеннями губи та піднебіння (ВНГП) починається від народження і триває до зрілого віку та вимагає мультидисциплінарного підходу. Кожен з етапів ортодонтичних втручань має певні особливості.
Мета дослідження – провести біомеханічне обґрунтування принципів ортодонтичного лікування пацієнтів з однобічними ВНГП.
Матеріали і методи. Проаналізовано міждисциплінарний підхід та наведено біомеханічне обґрунтування принципів ортодонтичного лікування 137 дітей (середній вік (9,3±4,2) року) на прикладі пацієнта Р., який звернувся до клініки у віці 5 роки з діагнозом вродженого лівобічного наскрізного незрощення верхньої губи, альвеолярного відростка, твердого та м’якого піднебіння після хейлоринопластики та велопластики.
Результати досліджень та їх обговорення. Комплексне діагностичне обстеження пацієнтів із ВНГП включало збір анамнезу, клінічні суб’єктивні та об’єктивні методи. Створено імітаційну та дискретну моделі для моделювання переміщень частин біомеханічної системи, що включала ортодонтичний апарат та верхню щелепу, при впливі кутових рухів на 360°. При цьому використано розраховані вектори сил з амплітудою 50 Н. Визначено рентгенологічну щільність (РЩ) компактного шару кісткової тканини при дії навантажень. Виявлено характерні особливості формування зубощелепних деформацій (ЗЩД) у пацієнтів із ВНГП та динаміку їх ортодонтичного лікування за допомогою морфометричних та антропометричних вимірів сканованих моделей щелеп.
Висновки. При лікуванні дітей із ВНГП важливим є дотримання скоординованого алгоритму реабілітації, успіх залежить від своєчасних та топографо-функціональних підготовлених хірургічних втручань і послідовної ортодонтичної корекції з визначенням закономірностей змін напружено-деформованого стану та величин деформаційних зміщень незрощених фрагментів верхньої щелепи.
ВЕДЕННЯ ВАГІТНОСТІ У ЖІНОК ІЗ ВИЛІКУВАНИМ БЕЗПЛІДДЯМ НА ТЛІ СИНДРОМУ ГІПЕРПРОЛАКТИНЕМІЇ
Authors: Носенко О. М. , Мартиновська О. В.
Published: August 2024

Мета дослідження – визначити особливості перебігу вагітності та пологів у жінок із вилікуваним безпліддям внаслідок синдрому гіперпролактинемії (СГПРЛ) на тлі ідіопатичної гіперпролактинемії (ІГ) або мікропролактином (МП) й ефективність гормональної підтримки такої вагітності дидрогестероном.
Матеріали та методи. Спостереження охоплювало 78 безплідних жінок із СГПРЛ внаслідок МП або ІГ, у яких внаслідок лікування каберголіном настала вагітність. Після настання вагітності жінки основної групи О (n=32) отримували дидрогестерон до 20 тижнів вагітності, вітамінно-мінеральні комплекси, при високих цифрах сироваткового пролактину (ПРЛ) – каберголін до нормалізації рівнів ПРЛ; жінок групи порівняння П (n=30) вели відповідно до існуючих стандартів ведення вагітності. Контрольну групу К склали 30 умовно здорових фертильних жінок без нейроендокринних порушень. Досліджено гормональний профіль сироватки периферичної крові в динаміці лікування безпліддя, сироваткові рівні ПРЛ у терміни вагітності 11–12, 18–20, 30–31 і 36–37 тижнів, результати перебігу вагітності та пологів.
Результати дослідження та їх обговорення. До початку лікування гормональний статус безплідних жінок із СГПРЛ характеризувався підвищеним рівнем ПРЛ та вільного тестостерону, зниженими сироватковими концентраціями фолікулостимулювального та лютеїнізуючого гормонів, естрадіолу та прогестерону. Безперервне лікування каберголіном займало в середньому (6,21±0,16) міс. Овуляція відновилася через (5,27±0,13) міс. Вагітність була досягнута при СГПРЛ через (8,04±0,19) міс. Проведення запропонованого лікування привело у групі О до зниження частоти загрози викидня у 3,47 раза (СШ 0,1868 [0,0610–0,5723]), дисфункції плаценти у 5,07 раза (CШ 0,0827 [0,0266–0,2567]), викиднів у 12,92 раза (CШ 0,0585 [0,0069–0,4971]), передчасного розриву плодових оболонок у 3,60 раза (CШ 0,2121 [0,0585–0,7686]). Передчасні пологи у групі П були у 36,36 % випадків, у групі О усі пологи були терміновими (p<0,01).
Висновки. Тривале лікування каберголіном у жінок із безпліддям на тлі ІГ та МП відновлює фертильність, а застосування дидрогестерону в першій половині вагітності призводить до вірогідного зниження гестаційних та акушерських ускладнень.
Value co-creation for memorable touristic experiences: experimental evidence of the effects on consumer satisfaction and purchase intention
Authors: Fortunato Luiz Filipe Naressi , Sarfati Gilberto , Dallabrida Yuri Marcel
Published: August 2024

The integration of the Internet with other technologies has profoundly impacted consumer relations in the tourism and hospitality industry, enabling disintermediation and direct consumer access to service providers. In this challenging scenario, travel agencies may strategically tailor touristic services and deliver memorable experiences by engaging consumers in cocreating their travel itineraries. This study tests the hypothesis that involvement in a co-creation process with a tourist service provider positively affects consumer satisfaction and purchase intention. An experimental study was conducted to assess this, and the results supported the hypotheses. Moreover, practical implications are provided for travel agents operating both online and offline to enhance their competitiveness by incorporating co-creation processes into their routines, which can increase consumers’ perceived value.