bluuebunny/crossref_metadata_2025 huggingface dataset:
PD-1 cis-targeted IL-2v in combination with radiotherapy inhibits lung cancer growth and remodels the immune microenvironment
Authors: Godfroid Céline , Romero Jackeline , Labiano Sara , Chuang Chia-Hsien , Kelemen Andrea , Wyss Tania , Roh Vincent , Verdeil Grégory , Klein Christian , Codarri Deak Laura , Umaña Pablo , Tolstonog Genrich V , Trumpfheller Christine , Vozenin Marie-Catherine , Romero Pedro J
Published: January 2025

Background

More efficient therapeutic options for non-small cell lung cancer (NSCLC) are needed as the survival at 5 years of metastatic disease is near zero. In this regard, we used a preclinical model of metastatic lung adenocarcinoma (SV2-OVA) to assess the safety and efficacy of novel radio-immunotherapy combining hypofractionated radiotherapy (HRT) with muPD1-IL2v immunocytokine and muFAP-CD40 bispecific antibody.

Methods

We evaluated the changes in the lung immune microenvironment at multiple timepoints following combination therapies and investigated their underlying antitumor mechanisms. Additionally, we analyzed the tumor clonal heterogeneity upon the combination treatments to explore potential mechanisms associated with the lack of complete response.

Results

The combination of HRT with muPD1-IL2v had a potent antitumor effect and increased survival in the SV2-OVA lung cancer model. Importantly, this combination therapy was devoid of measurable toxicity. It induced remodeling of the immune contexture through the increase of CD8+T and natural killer (NK) cells. The addition of muFAP-CD40 to the combination treatment further increased infiltrating CD8+T cells, expressing high levels of effector molecules, both in the periphery and core tumor regions. An accumulation of CD8+PD-1+TOX+(exhausted) T cells, already at the ‘early’ timepoint, is consistent with the limited clinical benefits provided by the various combination treatments in this model. The study of the clonal dynamics of tumor cells during disease progression and therapy highlighted a clonal selection upon HRT+muPD1-IL2v therapy.

Conclusions

We demonstrated that HRT+muPD1-IL2v combination is a potent therapeutic strategy to delay tumor growth and increase survival in a metastatic lung cancer model, but additional studies are required to completely understand the resistance mechanisms associated with the lack of complete response in this model.
Computational study of the wake of a plane bluff body with a gap flow—mean velocity characteristics
Authors: Shinneeb A.-M. , Nasif G. , Balachandar R.
Published: January 2025

This numerical study investigates the shallow wake characteristics behind a vertical flat plate with and without gap flow. It builds upon our prior experimental work on bluff wakes to gain deeper understanding of the flow. Using transient three-dimensional Navier–Stokes equations solved via finite-volume approach with improved delayed detached eddy simulation turbulence model, it provides spatial and temporal data for the wake volume. The bulk velocity was 0.45 m/s, yielded a Reynolds number of 45 000. This paper marks the initial phase of an extensive investigation aimed at characterizing the impact of gap flow on the mean velocity field. The results revealed the formation of a three-dimensional mean recirculation loop just behind the bluff body whose shape resembles a hairpin vortex loop. The gap flow reduces the vortex loop diameter and increases its spinning strength. Moreover, it hinders the secondary currents causing delayed wake spread near the bed but enhances the secondary flow in the upper velocity fields and hence, the growth rate.
Effect of temperature distribution and thermal gradient on the thermal response of steel–concrete composite girders
Authors: Nayeem Mostansir Billah , Billah AHM Muntasir
Published: January 2025

Thermal loads significantly influence bridge performance, particularly in extreme climates. This study identified a significant scope for investigating how changes in constituent material strength influence the overall temperature field and affect stress distribution in composite bridges. Also, this study focuses on investigating the thermal effects on steel–concrete composite bridges, an area that hasn't been extensively explored compared to concrete or steel bridges. The objective is to develop an efficient finite element (FE) model to simulate temperature variations and their impact on composite bridge girders considering varying concrete strengths. It involves developing an experimentally validated FE model of a dimensionally reduced steel–concrete composite bridge girder to assess the structural effects of a 24 h simulated temperature field through a sequentially coupled thermo-mechanical analysis technique in Abaqus. The findings indicate that under similar thermal boundary conditions, composite bridge girder specimens with varying concrete strengths exhibit differences in stress values.
Impact of single and combined soil amendments on the growth and foliar nutrients of white spruce (Picea glauca) on a poorly regenerated logged site.
Authors: Merzouki Hiba , Poirier Vincent , Munson Alison D. , Pare David , Desrochers Annie
Published: January 2025

Regeneration failure is occasionally encountered in the boreal mixed forest following clear-cutting, primarily due to competing vegetation and altered soil conditions. This study investigates the effects of applying several soil amendments to improve white spruce plantation growth on poorly regenerated forest sites. Biochar (2.6 Mg ha-1), wood ash (7 Mg ha-1), and manure (105 Mg ha-1) were used alone or in combination, with effects on foliar elements and seedling growth assessed after two growing seasons. While biochar and wood ash have been frequently used, combining them with manure has been limited in boreal forests. Using a randomized complete block design, we measured soil pH, incident light, seedling growth, specific leaf area, and foliar nutrition. Manure significantly increased seedling growth (+37%) compared to treatments without it. It also increased foliar nitrogen (+17%) and phosphorus (+14%). Wood ash increased foliar nitrogen (+7%), phosphorus (+15%), potassium (+19%) and calcium (+29%). Biochar, without wood ash, decreased foliar aluminum by 56%. We conclude that manure represented an important nitrogen and phosphorus source for seedling growth. This research highlights the potential of amendment combinations for improving growth and foliar nutrition of seedlings in poorly regenerated boreal forest ecosystems, for example where herbicide use is prohibited.
How analogies helped novice students think about superposition states and collapse in quantum mechanics
Authors: Faletič Sergej
Published: January 2025

In my active learning course on quantum mechanics, students build their knowledge by following the scientific process as outlined by the Investigative Science Learning Environment. In this course, open-ended questions on the effect of measurement (collapse) failed to elicit meaningful responses from students. Meaningful responses are crucial for the next steps of testing students’ ideas using hypothetico-deductive reasoning. I wanted to help the students in this process with a pictorial representation. To arrive at a pictorial representation that would have meaning for students, I first asked them to provide their analogies for a superposition state. A common suggestion was the mixture of colours, but other, more inventive analogies were also suggested. I developed a pictorial representation based on the colour analogy. I reformulated the questions on collapse using this representation and a more concretized formulation. The ability of students to meaningfully answer the questions increased to the point where it was possible to complete also the testing part of the process. In the article, I discuss the analogies that students suggested and what underlying ideas known from literature they could represent. I provide the derived representation, the reformulated questions and evidence of how this helped students articulate their answers and helped identify students’ productive ideas that they could not clearly articulate in words. This enabled students to arrive at conclusions about the effect of measurement following the scientific process. This study contributes to the literature by providing student-generated analogies, using a pictorial representation derived from student-generated analogies, and showing an example of an efficiently formulated question on a difficult topic that is able to elicit meaningful responses.
CONGENITAL CLASPED THUMB DEFORMITY IN CHILDREN: CASE REPORT
Authors: Megremis Panos K. , Megremis Orestis P.
Published: January 2025

The objective of this case report is to emphasize the importance of the identification of all the causative factors responsible for the creation of the congenital clasped thumb, as their detection will perform a critical part in the choice of the proper surgical treatment. This study presents the case of a four-year-old boy with a congenital clasped thumb of the right hand. A short Flexor Pollicis Longus (FPL), an absent Abductor Pollicis Longus (APL), a hypoplastic Extensor Pollicis Brevis (EPB), and palmar displacement of the Extensor Pollicis Longus (EPL) were detected. The surgical treatment included Z-lengthening of the short FPL and augmentation of the insufficient EPL and EPB by tendons transfer. Postoperatively, the thumb was halted in a place of full radial abduction and [Formula: see text] of palmar flexion with scotchcast plaster for four weeks. In his last follow-up three years after surgery, he was able to do full abduction and extension of the thumb. He was able to open a door or grasp and hold various objects. He was fully satisfied with the result of the operation. Treatment should be adjusted to address all causative issues of clasped thumb effectively, reduce deforming forces, and increase the activity of insufficient muscles.
Fourier–Galerkin approximation of the solutions of the 2D Euler equations with bounded vorticity
Authors: Berselli Luigi C. , Spirito Stefano
Published: January 2025

In this paper we prove the uniform-in-time [Formula: see text] convergence for the Fourier–Galerkin approximation to Yudovich solutions of the 2D Euler equations. Precisely, we show that both the approximating velocity and the approximating vorticity converge strongly in [Formula: see text]. Moreover, for the convergence of the velocity we provide an explicit rate of convergence. The proofs are based on a relative entropy approach and the Osgood lemma. Related results under different assumptions on the vorticity are also proved.
Explicit solutions and linear inviscid damping in the Euler–Boussinesq equation near a stratified Couette flow in the periodic strip
Authors: Coti Zelati Michele , Nualart Marc
Published: January 2025

This short note provides explicit solutions to the linearized Boussinesq equations around the stably stratified Couette flow posed on [Formula: see text]. We consider the long-time behavior of such solutions and prove pointwise inviscid damping of the perturbed density and velocity field for any positive Richardson number, with optimal rates. The explicit solution is obtained through the limiting absorption principle whereas the inviscid damping is proved using oscillatory integral methods.
Oleinik-type estimates for nonlocal conservation laws and applications to the nonlocal-to-local limit
Authors: Coclite Giuseppe Maria , Colombo Maria , Crippa Gianluca , De Nitti Nicola , Keimer Alexander , Marconi Elio , Pflug Lukas , Spinolo Laura V.
Published: January 2025

We consider a class of nonlocal conservation laws with exponential kernel and prove that quantities involving the nonlocal term [Formula: see text] satisfy an Oleĭnik-type entropy condition. More precisely, under different sets of assumptions on the velocity function [Formula: see text], we prove that [Formula: see text] satisfies a one-sided Lipschitz condition and that [Formula: see text] satisfies a one-sided bound, respectively. As a byproduct, we deduce that, as the exponential kernel is rescaled to converge to a Dirac delta distribution, the weak solution of the nonlocal problem converges to the unique entropy-admissible solution of the corresponding local conservation law, under the only assumption that the initial datum is essentially bounded and not necessarily of bounded variation.
Facile fabrication of PEG-PPG block copolymer via Michael addition reaction and its successful application as all-solid-state electrolyte for rechargeable lithium metal batteries
Authors: Wang Wanhui , Hu Ji
Published: January 2025

Polyethylene glycol (PEG) is one of the most popular polymer matrices for fabricating solid polymer electrolytes (SPEs), and the derived lithium metal batteries (LMBs) exhibit a charming application potential in the field of energy storage and conversion materials. Nevertheless, the semicrystalline nature at ambient temperature of PEG poses significant challenges for its direct utilization in SPEs, thereby impeding its feasibility for commercial application. Herein, a copolymer backbone composed of PEG and polypropylene glycol (PPG) was successfully synthesized via aza-Michael addition reaction, and the SPEs were obtained by introducing stoichiometric content of lithium salt by means of a solution casting process. Benefiting from the doping effect of PPG in the system, the regularity of PEG chain is perturbed, which promotes the room-temperature ionic conductivity of SPEs to 3.62 × 10[Formula: see text]S cm[Formula: see text], while its electrochemical oxidation potential is as high as 5.73 V. Consequently, the SPEs have a good compatibility with both LiFePO4 and LiNi[Formula: see text]Co[Formula: see text]Mn[Formula: see text]O2, and the assembled all-solid-state LMBs demonstrate good cycling performance.
Silicate weathering, land plants and cooling in the late Silurian and early Devonian
Authors: Avila T. D. , Saltzman M. R. , Griffith E. M. , Joachimski M. M.
Published: January 2025

The development of terrestrial vegetation and its impact on silicate weathering is hypothesized to have driven multiple cooling events throughout the Paleozoic. One such event is the 8–10°C cooling observed from the late Silurian to early Devonian (
c
. 420–385 Ma). Chemical weathering of Ca- and Mg-bearing silicate minerals and the subsequent trapping of carbon in marine carbonates are a sink for atmospheric CO
2
on multimillion-year time scales. The strontium isotopic ratio (
87
Sr/
86
Sr) of seawater acts as a geochemical proxy for this process. In this study, we present new Silurian to Devonian
87
Sr/
86
Sr data paired with oxygen isotopes (

δ

18
O; a proxy for palaeotemperature and ice volume) from conodont apatite. The two datasets show an inflection in the late Silurian to early Devonian, suggesting a connection between enhanced basaltic weathering (leading to lower
87
Sr/
86
Sr) and cooling (increasing

δ

18
O). The spread of terrestrial plants probably drove a significant portion of the enhanced basaltic weathering, which would have driven cooling, in addition to coeval tectonic changes in the Pridoli Epoch (422.7–419.0 Ma) and Lochkovian Age that further enhanced weathering and drawdown of atmospheric CO
2
(419.0–412.4 Ma).
Toward Digital Life: Embracing, Complicating, and Reconceptualizing Digital Literacy in Communication Design
Authors: Stambler Danielle Mollie , Veeramoothoo Saveena (Chakrika) , Davis Katlynne
Published: January 2025

This article is the introduction to the
Communication Design Quarterly
special issue on digital life. It explains the exigency for this issue and details how digital literacies in technical and professional communication are complicated by emerging technologies. It also demonstrates the potential for moving toward a model of digital life as a flexible way of foregrounding and talking about the work we are all already doing to understand and improve our post-human lives.
Biodigital Literacy through Intimate Data: User Perceptions of FemTech and Pelvic Floor Training Devices
Authors: Swartz Haley
Published: January 2025

The FemTech industry, a booming segment of the health technology market, trades in feminist empowerment largely by data tracking and collection. As issues of privacy and surveillance related to users' data collection have grown, scholars in health, design, and communication have explored how health-related technologies complicate the liberatory potential of self-tracking and self-monitoring health, signaling digitally collected, intimate data as concerning and gesturing toward critical digital literacy as a requirement for technology users. By analyzing user comments about pelvic floor training devices, this article reframes intimate data to understand the ways that people create and use it to learn about themselves. This move demonstrates a new kind of literacy: biodigital literacy, which I offer as a concept and framework that highlights the unique competencies of embodied digital life.
(Re)Designing Privacy Literacy in the Age of Generative AI
Authors: Woods Charles , Johnson Gavin P.
Published: January 2025

In this article, we propose (re)designing privacy literacy as an essential component of our digital lives in an age of Generative Artificial Intelligence (genAI). Our study emphasizes the layered digital, technical, rhetorical, and algorithmic literacies associated with design thinking and genAI to support theorizing privacy literacy. We introduce
Design
as an analytical element complementary to Woods and Wason's (2021) multi-pronged framework for analyzing Terms of Service (ToS) documents. Using a cluster of Adobe Generative AI ToS, we illustrate the necessity of including
Design
, which allows those invested in Communication Design (CD) and Technical and Professional Communication (TPC) to interrogate how or if design supports or undermines values related to user privacy, data ownership, and informed consent. We conclude by detailing how collective surveillance apathy regarding emergent data infrastructures signal a Post-Surveillance era in our global society and digital lives.
Teaching Liberatory Design
Authors: Johnson Emily K.
Published: January 2025

This experience report describes a fully online graduate course on user-centered design that was designed to scaffold self-regulated learning and then redesigned to follow Anaissie et al.'s 2021 iteration of the Liberatory Design process. The pivot to Liberatory Design helped strengthen the self-regulated learning scaffolding, as each phase of the Liberatory Design process includes the processes of noticing, reflecting, and seeing the system. This article describes the prompts incorporated into major assignments, student perceptions, lessons learned, and the ways that Liberatory Design and self-regulated learning prompting can be used throughout the user-centered design process to improve the work of designers.
Towards Scene-Centric Multi-Level Interest Mining for Video Recommendation
Authors: Chen Jiayue , Wang Xiaomeng , Xu Tong , Wu Shiwei
Published: January 2025

Knowledge-aware video recommendation requires the ability of associating external knowledge to capture high-order connectivities between users and videos. One limitation of existing methods is that they only extract user interests at a granular level of relational paths by modeling high-order connectivities, which are coarse-grained in user interest modeling, failing to identify user-video relations at a finer-grained level of semantics. In this paper, we investigate the utility of semantic scene graphs in video recommendation scenario, which provide detailed, graph-based annotations of social situations depicted in video clips. We propose a new method named
Scene-Centric multi-level Interest Miner
(SCIMiner) which explicitly models multi-level user interests. Specifically, we construct user-video graph, knowledge graph and semantic scene graphs as hierarchical heterogeneous graphs. On top of the hierarchical graph representation, we propose two information aggregation strategies to capture user interests from different levels. Knowledge-aware aggregation scheme extracts coarse-grained user interests by aggregating relational paths in high-order connectivities, while scene-aware aggregation scheme models fine-grained user interests by capturing clip-level semantic commonality of user favorite videos. Furthermore, we adaptively distill complementary information about multi-level user interests extracted by different aggregation schemes and encode them into the representations of users and videos. Empirical results show that SCIMiner significantly outperforms the state-of-the-art methods. Further studies verify the complementary benefits of knowledge graph with semantic scene graphs in video recommendation scenario and the finer-grained explainability for predictions.
Capillary Electrophoresis–Mass Spectrometry for Top-Down Proteomics
Authors: Wang Qianjie , Wang Qianyi , Zhu Guijie , Sun Liangliang
Published: January 2025

Mass spectrometry (MS)-based top-down proteomics (TDP) characterizes proteoforms in cells, tissues, and biological fluids (e.g., human plasma) to better our understanding of protein function and to discover new protein biomarkers for disease diagnosis and therapeutic development. Separations of proteoforms with high peak capacity are needed due to the high complexity of biological samples. Capillary electrophoresis (CE)-MS has been recognized as a powerful analytical tool for protein analysis since the 1980s owing to its high separation efficiency and sensitivity of CE-MS for proteoforms. Here, we review benefits of CE-MS for advancing TDP, challenges and solutions of the method, and the main research areas in which CE-MS-based TDP can make significant contributions. We provide a brief perspective of CE-MS-based TDP moving forward.
First-in-Human Phase I Study of a CD16A Bispecific Innate Cell Engager, AFM24, Targeting EGFR-Expressing Solid Tumors
Authors: El-Khoueiry Anthony , Saavedra Omar , Thomas Jacob , Livings Claire , Garralda Elena , Hintzen Gabriele , Kohlhas Laura , Vanosmael Dessislava , Koch Joachim , Rajkovic Erich , Ravenstijn Paulien , Nuciforo Paolo , Fehniger Todd A. , Foster Mark , Berrien-Elliott Melissa M. , Wingert Susanne , Stäble Sina , Morales-Espinosa Daniela , Rivas Delcia , Emig Michael , Lopez Juanita
Published: January 2025

Purpose:

Innate immune cell–based therapies have shown promising antitumor activity against solid and hematologic malignancies. AFM24, a bispecific innate cell engager, binds CD16A on NK cells/macrophages and EGFR on tumor cells, redirecting antitumor activity toward tumors. The safety and tolerability of AFM24 were evaluated in this phase I/IIa dose-escalation/dose-expansion study in patients with recurrent or persistent, advanced solid tumors known to express EGFR.

Patients and Methods:

The main objective in phase I was to determine the MTD and/or recommended phase II dose. The primary endpoint was the incidence of dose-limiting toxicities during the observation period. Secondary endpoints included the incidence of treatment-emergent adverse events and pharmacokinetics.

Results:

In the dose-escalation phase, 35 patients received AFM24 weekly across seven dose cohorts (14–720 mg). One patient experienced a dose-limiting toxicity of grade 3 infusion-related reaction. Infusion-related reactions were mainly reported after the first infusion; these were manageable with premedication and a gradual increase in infusion rate. Pharmacokinetics was dose-proportional, and CD16A receptor occupancy on NK cells approached saturation between 320 and 480 mg. Paired tumor biopsies demonstrated the activation of innate and adaptive immune responses within the tumor. The best objective response was stable disease in 10/35 patients; four patients had stable disease for 4.3 to 7.1 months.

Conclusions:

AFM24 was well tolerated, with 480 mg established as the recommended phase II dose. AFM24 could be a novel therapy for patients with EGFR-expressing solid tumors, with suitable tolerability and appropriate pharmacokinetic properties for further development in combination with other immuno-oncology therapeutics.
The Impacts of Active and Inactive Ghrelin on Cachexia and Immune Checkpoint Inhibitor Monotherapy in Patients with Non-small Cell Lung Cancer
Authors: Murata Daiki , Azuma Koichi , Nishii Yuuya , Murotani Kenta , Matama Goushi , Kawahara Akihiko , Tokito Takaaki , Sasada Tetsuro , Hoshino Tomoaki
Published: January 2025

Background: Identifying the underlying mechanisms of immune checkpoint inhibitor resistance in patients with cachexia is a current challenge. Ghrelin is a peptide hormone that plays an important role in the metabolism of patients with cancer cachexia. Despite the importance of ghrelin in cancer cachexia, most previous studies on the subject have not distinguished between the forms of ghrelin. Material and Methods: We retrospectively screened patients with advanced or recurrent non-small cell lung cancer receiving PD-1/PD-L1 inhibitor monotherapy. Active and inactive ghrelin levels were measured in 100 patients with available plasma samples at immune checkpoint inhibitor initiation. Cancer cachexia was defined as weight loss of at least 5% during the past 6 months or weight loss of at least 2% with a BMI < 20. We analyzed the associations of the active and inactive ghrelin levels and active-to-inactive ghrelin ratio (AIR) with cancer cachexia. The prognostic impact of the active and inactive ghrelin levels and AIR were also analyzed. Results: Among 100 patients, 35 were diagnosed with cancer cachexia. The active ghrelin level and AIR were significantly associated with cancer cachexia, whereas the inactive ghrelin level was not. The active and inactive ghrelin levels and AIR were not associated with patient prognosis. Conclusions: The active ghrelin level and AIR were associated with cancer cachexia but not with patient prognosis. The function of the active and inactive forms of ghrelin may differ in cancer patients. The form of ghrelin should be clearly mentioned in relevant studies on cancer cachexia.
МАРКЕТИНГОВИЙ АНАЛІЗ ЛІКАРСЬКИХ ЗАСОБІВ ВІД НУДОТИ ТА БЛЮВОТИ
Authors: Bobenchyk M. M. , Levytska O. R. , Hromovyk B.  P. , Chukhray I.  L. , Jarko N. B.
Published: January 2025

Мета роботи. Розвідка асортименту і цінових пропозицій на вітчизняному фармацевтичному ринку лікарських засобів групи А04 Протиблювотні засоби та препарати, що усувають нудоту.
Матеріали та методи. Матеріали: Державний реєстр лікарських засобів України, інформація про величину визначеної добової дози, мінімальні та максимальні роздрібні ціни на лікарські засоби групи А04 в аптеках м. Львова станом на 30.11.2023 р. (період 1) та 28.02.2024 р. (період 2). Методи: інформаційного пошуку, аналізу, узагальнення, маркетингових досліджень.
Результати та обговорення. З’ясовано, що у періоді 1 в Україні було зареєстровано 46, а у періоді 2 – 49 асортиментних позицій лікарських засобів групи А04. Більшість з них були препаратами ондансетрону (65,2 % і 61,2 % відповідно). Число вітчизняних асортиментних позицій зменшилася з 56,5 % до 53,1 % внаслідок збільшення асортиментних позицій імпортного виробництва. За лікарськими формами в обидвох періодах переважали розчини для інфузій і таблетки.
На прикладі асортиментних позицій ондансетрону з’ясовано, що їх цінова пропозиція в аптеках м. Львів за час дослідження зменшилась на 17,7 % (з 3101 до 2552). При цьому були відсутні аптеки, які би пропонувати усі асортиментні позиції  ондансетрону. Виявлено невисокий рівень конкуренції та недостатню економічну доступність більшості асортиментних позицій ондансетрону.
Висновки. Досліджено тенденції асортиментної та цінової характеристики лікарських засобів групи А04 Протиблювотні засоби та препарати, що усувають нудоту на вітчизняному фармацевтичному ринку.
Vascular HIF2 Signaling Prevents Cardiomegaly, Alveolar Congestion, and Capillary Remodeling During Chronic Hypoxia
Authors: Albendea-Gomez Teresa , Mendoza-Tamajon Susana , Castro-Mecinas Rosana , Escobar Beatriz , Ferreira Rocha Susana , Urra-Balduz Sonia , Nicolas-Avila Jose Angel , Oliver Eduardo , Villalba-Orero Maria , Martin-Puig Silvia
Published: January 2025

BACKGROUND:

Hypoxia is associated with the onset of cardiovascular diseases including cardiac hypertrophy and pulmonary hypertension. HIF2 (hypoxia inducible factor 2) signaling in the endothelium mediates pulmonary arterial remodeling and subsequent elevation of the right ventricular systolic pressure during chronic hypoxia. Thus, novel therapeutic opportunities for pulmonary hypertension based on specific HIF2 inhibitors have been proposed. Nevertheless, HIF2 relevance beyond the pulmonary endothelium or in the cardiac adaptation to hypoxia remains elusive. Wt1 (Wilms tumor 1) lineage contributes to the heart and lung vascular compartments, including pericytes, endothelial cells, and smooth muscle cells.

METHODS:

Here, we describe the response to chronic hypoxia of a novel HIF2 mutant mouse model in the Wt1 lineage (
Hif2/Wt1
cKO [conditional knockout]), characterizing structural and functional aspects of the heart and lungs by means of classical histology, immunohistochemistry, flow cytometry, echocardiography, and lung ultrasound analysis.

RESULTS:

Hif2/Wt1
cKO is protected against pulmonary remodeling and increased right ventricular systolic pressure induced by hypoxia, but displays alveolar congestion, inflammation, and hemorrhages associated with microvascular instability. Furthermore, lack of HIF2 in the Wt1 lineage leads to cardiomegaly, capillary remodeling, right and left ventricular hypertrophy, systolic dysfunction, and left ventricular dilation, suggesting pulmonary-independent cardiac direct roles of HIF2 in hypoxia. These structural defects are partially restored upon reoxygenation, while cardiac functional parameters remain altered.

CONCLUSIONS:

Our results indicate that cardiopulmonary HIF2 signaling prevents excessive vascular proliferation during chronic hypoxia and define novel protective roles of HIF2 to warrant stable microvasculature and organ function.
Classifying Race in Out-of-Hospital Cardiac Arrest and Potential Disparities: A Retrospective Cohort Study
Authors: Shin Jenny , Liu Jennifer , Parayil Megin , Counts Catherine R. , Drucker Christopher J. , Coult Jason , Blackwood Jennifer , Guan Sally , Kudenchuk Peter J. , Sayre Michael R. , Rea Thomas
Published: January 2025

BACKGROUND:

Although racial disparities have been described in resuscitation, little is known about potential bias in race classification of out-of-hospital cardiac arrest (OHCA).

METHODS:

We conducted a retrospective cohort study of adults treated by emergency medical services (EMS) for nontraumatic OHCA in King County, WA between January 1, 2018, and December 31, 2021. We assessed agreement using κ and evaluated patterns of missingness between EMS-assessed race versus comprehensive race classification from hospital and death records. Using multivariable logistic regression adjusting for Utstein data elements, we analyzed the association between race and OHCA survival across different sources.

RESULTS:

Among 5909 eligible OHCA patients, the average age was 64.0 years, 35.4% were female, and 16.1% survived to hospital discharge. Based on comprehensive race classification, 68.7% were White, 12.8% Black, 12.1% Asian, 2.5% multiracial, 2.3% Native Hawaiian/other Pacific Islander, and 1.6% American Indian/Alaska Native. EMS did not classify race in 43.7%. The κ coefficient between EMS and comprehensive race classification was 0.88 (95% CI, 0.86–0.90), though agreement varied substantially by specific race and was lowest among American Indian/Alaska Native (39.5%). Missingness in EMS records varied according to race and was greater among those classified as American Indian/Alaska Native (60.8%), Native Hawaiian/other Pacific Islander (58.8%), Asian (57.8%), or multiracial (54.1%) compared with White (40.6%) or Black (40.4%). In multivariable models using EMS-classified race, the odds ratio (OR) of survival was not significantly different for any race group compared with the White race, that is, OR. However, when using comprehensive race classification, OR of survival was significantly lower among Native Hawaiian/other Pacific Islander (OR, 0.57 [95% CI, 0.33–0.97]) and among multiracial (OR, 0.40 [95% CI, 0.20–0.75]) compared with White race.

CONCLUSIONS:

In adult OHCA, race misclassification and missingness influenced its association with survival. Efforts should continue to evaluate best practices to classify race correctly and comprehensively.
NEDD4–Mediated GSNOR Degradation Aggravates Cardiac Hypertrophy and Dysfunction
Authors: Tang Xin , Liu Xiameng , Sha Xinqi , Zhang Yan , Zu Yan , Fan Qiyao , Hu Lulu , Sun Shixiu , Zhang Zhiren , Chen Feng , Yan ChengHui , Chen Xin , Xu Yueyue , Chen Wen , Shao Yongfeng , Gu Jiaxi , Pu Jun , Yu Bo , Han Yaling , Xie Liping , Han Yi , Ji Yong
Published: January 2025

BACKGROUND:

The decrease in S-nitrosoglutathione reductase (GSNOR) leads to an elevation of S-nitrosylation, thereby exacerbating the progression of cardiomyopathy in response to hemodynamic stress. However, the mechanisms under GSNOR decrease remain unclear. Here, we identify NEDD4 (neuronal precursor cell expressed developmentally downregulated 4) as a novel molecule that plays a crucial role in the pathogenesis of pressure overload–induced cardiac hypertrophy, by modulating GSNOR levels, thereby demonstrating significant therapeutic potential.

METHODS:

Protein synthesis and degradation inhibitors were used to verify the reasons for the decrease in GSNOR. Mass spectrometry and database filtering were used to uncover NEDD4, the E3 Ub (ubiquitin) ligase, involved in GSNOR decrease. NEDD4 cardiomyocyte-specific deficiency mice were used to evaluate the role of NEDD4 and NEDD4–induced ubiquitination of GSNOR in cardiac hypertrophy in vivo. Both IBM (indolebutenate methyl ester derivatives), a highly specific NEDD4 inhibitor, and indole-3-carbinol, a NEDD4 inhibitor currently undergoing phase 2 clinical trial, were used to effectively suppress the NEDD4/GSNOR axis.

RESULTS:

GSNOR protein levels were reduced, while mRNA levels remained unchanged in myocardium samples from hypertrophic patients and transverse aortic constriction–induced mice, indicating GSNOR is regulated by ubiquitination. NEDD4, an E3 Ub ligase, was associated with GSNOR ubiquitination, which exhibited significantly higher expression levels in hypertrophic myocardial samples. Moreover, either the NEDD4 enzyme-dead mutant or GSNOR nonubiquitylated mutant decreased GSNOR ubiquitination and inhibited cardiac hypertrophic growth. Cardiomyocyte-specific NEDD4 deficiency inhibited cardiac hypertrophy in vitro and in vivo. NEDD4 inhibitor IBM effectively suppressed GSNOR ubiquitination and cardiac hypertrophy. Clinically, indole-3-carbinol, a NEDD4 inhibitor in phase II clinical trials used as an antitumor drug, demonstrated comparable efficacy.

CONCLUSIONS:

Our findings showed that upregulated NEDD4 leads to GSNOR ubiquitination and subsequent degradation, thereby facilitating the progression of cardiac hypertrophy. NEDD4 inhibitors may serve as a potential therapeutic strategy for the treatment of cardiac hypertrophy and heart failure.
Impact of Acute Myocardial Injury on Short‐ and Long‐Term Outcomes in Patients With Primary Intracerebral Hemorrhage
Authors: Ma Shenghui , Li Jiawen , Kong Qi , Xu Zhiming , Wu Haojie , Jin Yujia , Ye Xianghua , Luo Dong , Tong Lusha , Gao Feng
Published: January 2025

Background

Myocardial injury is common after brain injury; however, few studies have reported serial cardiac troponin (cTn) measurements to distinguish whether the myocardial injury is acute or chronic. The fourth Universal Definition of Myocardial Infarction introduced for the first time the criteria for acute myocardial injury (AMI). We aimed to investigate the prevalence and prognostic implications of AMI in primary intracerebral hemorrhage.

Methods and Results

We retrospectively analyzed patients with primary intracerebral hemorrhage within 48 hours after symptom onset. All patients included had at least 2 cTn measurements: 1 obtained at the time of emergency admission and at least 1 more within the first 2 days of hospitalization. AMI was defined as an elevated cTn above the upper‐reference limit (14 ng/L) along with a rise/fall >20%. Patients were followed for up to 5 years. Outcomes included major adverse cardiac events (MACEs; a composite of vascular death, nonfatal coronary events, and nonfatal stroke) and 90‐day unfavorable outcomes (modified Rankin scale score ≥4). Cox proportional hazards models, multivariable logistic regression models, and Kaplan–Meier analyses were used to evaluate the association between AMI and outcomes. Of 600 patients included, 115 had AMI (19.2%). AMI independently conferred an increased risk for major adverse cardiac events (adjusted hazard ratio, 1.69 [95% CI, 1.12–2.53]) and 90‐day unfavorable outcomes (adjusted odds ratio, 2.15 [95% CI, 1.26–3.67]) compared with patients without AMI.

Conclusions

AMI is relatively common in patients with intracerebral hemorrhage and is associated with both long‐term major adverse cardiac events and 90‐day unfavorable outcomes.
Monocyte to High‐Density Lipoprotein Ratio Is Associated With Carotid Plaque: A Retrospective Cohort Study
Authors: Liu Shuang , Miao Xinlei , Hu Manling , Song Ziping , Xie Xiaoling , Sun Yuting , Li Meng , Tang Guimin , Leng Song
Published: January 2025

Background

The level of monocyte to high‐density lipoprotein ratio (MHR) is associated with cardiovascular diseases. Carotid plaque (CP) is an independent risk factor for cardiovascular diseases. However, evidence for association of MHR with risk of CP is scarce.

Methods and Results

This study involved 5260 participants aged >18 years old from the Dalian health management cohort in 2014 to 2022. The subjects were stratified into 4 groups based on the quartile of the MHR at baseline. Multivariable‐adjusted Cox regression models were used to calculate the MHR‐associated risk of incident CP. The mean age of the population was 46.14 years and 58.8% (n=3093) of the participants were male. Seven hundred fifty‐nine (14.4%) of participants developed new‐onset CP. During the follow‐up of 9725 person‐years, the MHR at quartile 4 group experienced a significantly higher incidence of CP than the MHR at quartile 1 group (56.9 versus 101.5 per 1000 person‐years; log‐rank
P
<0.001). Compared with the MHR at quartile 1 group, the MHR at quartile 4 group had the highest CP risk (hazard ratio. 1.389 [95% CI, 1.059–1.823]) and 10‐year cardiovascular risk (China‐PAR Project score: odds ratio, 1.975 [95% CI, 1441–2.708 in men]; odds ratio, 6.015 [95% CI, 1.949–18.564 in women) (
P
<0.001). Meanwhile, similar results were observed in multiple sensitivity analyses.

Conclusions

Elevated MHR was associated with the risk of CP. The assessment and management of MHR is helpful for the early detection of patients with CP and the primary prevention of cardiovascular diseases.
Association Between Triglyceride–Glucose Index and Carotid Plaque Stability in Different Glycemic Status: A Single‐Center Retrospective Study
Authors: Huo Guijun , Zheng Jin , Cao Junjie , Zhang Lili , Yao Zhichao , Zeng Yuqi , Tang Yao , Liu Zhanao , Tan Ziyi , Zhou Dayong
Published: January 2025

Background

The triglyceride–glucose (TyG) index has been proposed as a reliable marker of insulin resistance. However, its value in patients with carotid plaque stability remains unclear. This study investigated the association between the TyG index and unstable carotid plaque.

Methods

A total of 12 068 participants were enrolled. Carotid ultrasound was used to determine the stability of carotid plaque. Logistic regression was used to analyze the relationship between the TyG index and unstable carotid plaque. The relationship between the TyG index and unstable carotid plaque was evaluated according to sex, age, and glucose metabolism states. Further, the dose–response relationship between the TyG index and unstable carotid plaque was also determined by restrictive cubic splines.

Results

Of the 12 068 participants, 11 601 had stable carotid plaque and 467 had unstable carotid plaque. In several different adjustment models, the TyG index is significantly related to the risk of unstable carotid plaque. The association between the TyG index and an unstable carotid plaque was similar between men and women, despite the fact that the odds ratio (OR) tended to be higher in men (OR, 2.80 [95% CI, 2.04–3.83]) than women (OR, 2.07 [95% CI, 1.51–2.82]), and higher in older patients (aged >60 years; (OR, 3.59 [95% CI, 2.74–4.70]) than middle‐aged patients (aged ≤60 years) (OR, 2.00 [95% CI, 1.36–2.95]). The TyG index of patients with different glycemic status was significantly correlated with the risk of unstable carotid plaque, among which the OR value of diabetes (OR, 2.51 [95% CI, 1.87–3.36]) was the highest. The restrictive cubic spline analysis indicated a nonlinear relationship between the TyG index and unstable carotid plaque, with TyG index >8.63 identified as an independent risk factor for unstable carotid plaque.

Conclusions

The TyG index has a significant association with unstable carotid plaque. The association between the TyG index and unstable carotid plaque is similar between men and women, and the association in older patients is higher than that in middle‐aged patients. In different glycemic status, the association between the TyG index and unstable carotid plaque is highest in patients with diabetes.
Introduction: New Directions in Roman Political Thought
Authors: West David T.
Published: January 2025

This short preface explains the context and purpose of the present volume. It also summarizes the diverse approaches and lines of argument pursued by the contributors.
Phylogenetic relationships within western African Torrent Toads (Anura: Bufonidae: Werneria) with focus on the taxonomic status of Werneria preussi and Atelopus africanus
Authors: PETZOLD ALICE , NORDEN VANESSA , GONWOUO NONO L. , SEGNIAGBETO GABRIEL H. , OHLER ANNEMARIE , RÖDEL MARK-OLIVER
Published: January 2025

Bufo preussi Matschie, 1893 from Mt. Cameroon was the first African Torrent toad to be described, soon followed by Atelopus africanus Werner, 1898 from Bismarkburg in Togo. Shortly after, both species were considered conspecific and, currently, both fall under the name Werneria preussi following taxonomic revisions. The type locality of A. africanus was consequently believed to be an error, especially due to the absence of reports of Werneria individuals in Togo in subsequent years. However, it remained uncertain if this synonymy is justified or if A. africanus may indeed represent a valid but potentially extinct species. To answer this question, we generated the first mitochondrial data (12S, 16S and COI) for name-bearing types of W. preussi and A. africanus using a museomic approach. This was further complemented by mitochondrial and nuclear data of contemporary relatives. Our multi-gene phylogeny inferred from mitochondrial data showed that W. preussi and A. africanus constitute a well-supported monophyletic group, which further includes W. submontana. Together with distance values falling below the commonly used species threshold of 3% for 16S and 6% for COI, this result provides strong evidence for A. africanus being a junior synonym of W. preussi, and the absence of this genus in Togo. It further indicates that W. submontana does not represent a species distinct from W. preussi, but rather a geographic variety differing morphologically from topotypic W. preussi. Due to this morphological differentiation, we propose to consider the W. submontana populations as a distinct subspecies and herein introduce the new name Werneria preussi submontana comb. nov. We further designate a lectotype for W. preussi, in order to increase nomenclatural stability and facilitate future research focusing on African Torrent Toads.
A new species of Sinonichnus Jałoszyński in China (Coleoptera, Staphylinidae, Scydmaeninae)
Authors: JAŁOSZYŃSKI PAWEŁ
Published: January 2025

Sinonichnus Jałoszyński is an endemic Chinese genus currently including only two species: S. yunnanensis (Jałoszyński, 2019) and S. leiodicornutus Jałoszyński, 2021. Both species occur in Yunnan. Sinonichnus montanus sp. nov. is described, based on a male specimen collected close to the type localities of the previously known species.
Two new species of genus Hemipsocus (Psocodea: ‘Psocoptera’: Hemipsocidae) from India
Authors: RAMESH GURUSAMY , BABU RAJAPPA , SUBRAMANIAN KUMARAPURAM A.
Published: January 2025

Two new species of Hemipsocus Selys-Longchamps, 1872 are described here based on specimens collected from the forests of Jharkhand, Kerala and Tamil Nadu states, India. The species, H. mockfordi sp. nov. and H. menoni sp. nov., are differentiated from other members of this genus by the following characteristics; the female subgenital plate with two apical lobes, the straight and strongly chitinized male paraproctal horn in H. mockfordi sp. nov. The male epiproct exhibits well-developed scales that extend from the anterior section towards the median region in H. menoni sp. nov.
A molecular-assisted taxonomic assessment of elasmobranch fishes (Chondrichthyes: Elasmobranchii) from south-eastern Arabia revisited
Authors: HENDERSON AARON C. , REEVE ALAN J. , JABADO RIMA W. , NAYLOR GAVIN J. P.
Published: January 2025

The first molecular-assisted assessment of shark and batoid taxonomy in the waters of south-eastern Arabia was undertaken almost a decade ago, at a time when many species lineages lacked clear resolution. Consequently, only tentative identifications could be offered in some cases. There has been a considerable amount of focus on elasmobranch taxonomy since then, and this has resulted in numerous revisions to species identities and distributions. Therefore, in light of these more recent findings, mitochondrial NADH2 sequences from the original south-eastern Arabia study were re-assessed and taxonomically updated. This resulted in the recovery of 28 distinct shark lineages, of which all but one could be attributed to currently-recognised species. The remaining lineage most likely represents an undescribed Echinorhinus sp., which has been flagged in previous studies. Twenty-eight batoid lineages were also recovered, 13 of which have undergone taxonomic revision since the original study. Although most of these could be attributed to currently-recognised species, certain lineages remain problematic. Consequently, further work is required to provide a comprehensive assessment of elasmobranch taxonomy in the region.
New species and host plants of Hexachaeta Loew (Diptera: Tephritidae) from Colombia
Authors: CLAVIJO PEDRO ALEXANDER RODRIGUEZ
Published: January 2025

Hexachaeta cundiboyacensis Rodriguez, a new species of the colombiana species group is described and illustrated. In addition, the first biological information on host plants and natural enemies for the colombiana species group is provided. Host plants include: Aegiphila alba Moldenke (Lamiaceae) for H. colombiana Lima and Aegiphila integrifolia (Jacq.) B.D. Jacks. (Lamiaceae) for the new species described here. The wasp Opius (Bellopius) hexachaeta Kula and Aguirre (Braconidae) was found parasitizing the new species. A modification of the species key of Hernández-Ortiz (1999) to incorporate this new species is also presented.
Strategic Communication for Achieving Health Outcomes Among Rural Tribes During COVID-19: An Experimental Study of Paniya Tribe in Kerala, India
Authors: EV Ranjith , Rai Shikha
Published: January 2025

Studies on global health communication have expanded to encompass scenarios that emerged as a result of the COVID-19 pandemic. This study examined how strategically planned communication improves tribe health. Data were collected from the target population using a quasi-experimental method. The compilation of video clips and implementation of an intervention were undertaken to carry out the experiment. COVID-19 awareness was the domain in which the video intervention has the potential to bring about changes in the current state of affairs. Except for cultural factors, the intervention was effective in communicating health information to the Indigenous population.