bluuebunny/crossref_metadata_2025 huggingface dataset:
CVLP-NaVD: Contrastive Visual-Language Pre-training Models for Non-annotated Visual Description
Authors: Li Haoran , Hao Yanbin , Yu Jiarui , Zhu Bin , Wang Shuo , Xu Tong
Published: December 2024

Non-annotated visual description (NaVD) aims to describe generic visuals without human-annotated pairwise data. The generic visuals refer to images and videos. Existing works mainly focus on one specific visual modality,
i.e.
, image or video. In this paper, we propose a new framework for this task, which can directly be applied to both image and video with the pipeline unchanged. Essentially, it is a unified framework that flexibly adapts to images and videos. Recently, contrastive visual-language pre-training models (CVLPs) have experienced rapid development, demonstrating powerful abilities to align vision and language. To continuously leverage advanced CVLPs, our framework is designed to work well with general CVLPs. It can easily use image-language CVLPs for image input and switch to video-language CVLPs for video input. Specifically, we propose a CVLP-based framework for NaVD, named CVLP-NaVD. It follows the paradigm of adversarial learning, containing a generator and a discriminator. The generator takes an image or a video as input and produces a corresponding language description, while the discriminator evaluates the generated sentence for its naturalness in human-like language. Apart from the naturalness, CVLPs play a crucial role in enhancing the alignment between visual and language signals during generation. Particularly, we explore three rewarding strategies to compute the alignment score, including directly calculating cosine similarity (
i.e.
, VL-cross), projecting visual embeddings into the textual domain (
i.e.
, VL-project) and their combination (
i.e.
, VL-mix). The three strategies are fully examined in different scenarios. Finally, we conduct extensive experiments with various unpaired and unsupervised setups in both image and video captioning tasks. The experimental results demonstrate that our CVLP-NaVD outperforms the state-of-the-art methods significantly.
Harnessing Machine Learning in Dynamic Thermal Management in Embedded CPU-GPU Platforms
Authors: Maity Srijeeta , Majumder Anirban , Roy Rudrajyoti , Hota Ashish , Dey Soumyajit
Published: December 2024

With increasing transistor density, modern heterogeneous embedded processors often exhibit high temperature gradients due to complex application scheduling scenarios which may have missed design considerations. In many use cases, off-chip ”active” cooling solutions are considered prohibitive in such reduced form factors. Core frequency throttling by existing dynamic thermal management techniques often compromises the Quality-of-Service (QoS) and violates real-time deadlines. This necessitates the adoption of intelligent resource management that simultaneously manages both thermal and latency performance. Coupled with the complexity of modern heterogeneous multi-cores, the periodic application updates that cater to ever-changing user requirements often render model-driven thermal-aware resource allocation approaches unsuitable for heterogeneous multi-core systems. For such application-architecture scenarios, we propose a novel self-learning based resource manager using Reinforcement Learning that intelligently manipulates core frequencies and task set mappings to fulfill thermal and latency objectives. Our framework employs a data-driven system modeling technique using Gaussian Process Regression to enable efficient offline training of this learning-based resource manager to avoid challenges associated with initial online training. We evaluate the approach on a heterogeneous embedded CPU-GPU platform with real workloads and observe a significant reduction in peak operating temperature when compared to the default onboard frequency governor as well as other learning-based state-of-the-art approaches.
Holographic Storage for the Cloud: advances and challenges
Authors: Cheriere Nathanaël , Chu Jiaqi , Brennan Grace , Cameron Pashmina , Da Costa Pedro , Gladrow Jannes , Ilunga Guilherme , Kelly Douglas , Lewis Sarah , Lim Joowon , Maltese Giorgio , Mason Tony , O'Shea Greg , Ponnapalli Soujanya , Rudow Michael , Sanders Alan , Stavrinos Theano , Wu Xingbo , Yang Mengyang , Narayanan Dushyanth , Thomsen Benn , Rowstron Antony
Published: December 2024

Holographic Storage is an old idea that has always promised high density and fast random access, but has never been commercially competitive with Hard Disk Drives (HDDs) and Solid State Devices (SSDs). In Project HSD at Microsoft Research we asked the question: “Does holographic storage finally make sense for cloud storage?” This article describes our journey toward answering this question.

We achieved 1.8× higher density than the previous state-of-the-art, using commodity components available today and leveraging machine learning to compensate for the noise and distortions introduced by commodity components. This uncovered two new challenges which are the focus of this article: achieving high end-to-end energy efficiency without sacrificing capacity, and spatial multiplexing without mechanical movement.

Improving end-to-end energy efficiency requires joint optimization across low-level media parameters and higher-level system parameters that govern background maintenance operations such as read refresh and garbage collection. We developed new physics models of the media; analytic and simulation models of the media access and background media maintenance; and workload-driven optimization to find optimal parameter combinations. These techniques resulted in a 14× improvement over the previous approach for typical workloads without sacrificing capacity. We also designed the first scalable and mechanical movement free spatial multiplexing system for holographic storage.

Despite these advances, we conclude that currently, holographic storage is still far from the combination of density, capacity scaling, and energy efficiency needed to compete with the incumbent technologies. We need fundamental advances in the physical media that improve energy efficiency by another 1–2 orders of magnitude without reducing data density. Further advances in optics are also required to achieve spatial multiplexing that is simultaneously scalable, low-loss, and high-density.
Context-Aware Proactive Self-Adaptation: A Two-layer Model Predictive Control Approach
Authors: Chen Zhengyin , Li Jialong , Li Nianyu , Jiao Wenpin , Kang Eunsuk
Published: December 2024

In self-adaptive software systems, the role of context is paramount, especially for proactive self-adaptation. Current research, however, does not fully explore context’s impact, for example on priorities of the requirements. To address this gap, we introduce a novel contextual goal model to capture these factors and their influence on the system. Using this, we propose a two-layer control mechanism with a context-aware model predictive control to achieve proactive adaptation for the software system and adaptation for the controller itself. By contextual prediction and a more accurate system model, our approach utilizes model predictive control to facilitate timely and efficient system adaptations, improving both performance and adaptability. Meanwhile, we perform requirement adaptation to update the contextual goal model, which in turn updates the objective function and constraints of the controller. Our experimental evaluations across two scenarios demonstrate the significant benefits of our approach in enhancing system performance.
Cascaded Alternating Refinement Transformer for Few-shot Medical Image Segmentation
Authors: Cheng Ziming , Zhu Yazhou , Wang Shidong , Xin Tong , Zhang Haofeng
Published: December 2024

Conventional biomedical image segmentation heavily relies on substantial annotations, which demand significant human and financial resources for collection. Consequently, learning a model with excellent performance using limited medical image data becomes a challenging problem. Upliftingly, the advent of few-shot medical image segmentation (FSMIS) offers a potential solution. Although prototypical networks are commonly employed in existing FSMIS tasks, the prototypes derived from support features often induce significant bias issues caused by intra-class variations. To this end, we propose a method called Cascaded Altering Refinement Transformer (CART) to iteratively calibrate the prototypes with both support and query features. This method focuses on capturing the commonality between foreground information of the support and query features using the Alterating Refinement Transformer (ART) module, which includes two Multi-head Cross Attention (MCA) modules. Furthermore, we cascade ART modules to refine the class prototypes, resulting in representative prototypes. This process ultimately contributes to a more accurate predicted mask. Besides, to preserve more valid information in each cascaded ART module and achieve better performance, we propose a novel inference method that accumulates the predicted segmentation masks in all ART modules by applying the Rounding-Up strategy. Extensive experiments on three public medical image datasets demonstrate that our model outperforms the state-of-the-art methods, and detailed analysis also validates the reasonableness of this design. Code is available at:
https://github.com/zmcheng9/CART
.
Multimodal Large Language Model with LoRA Fine-Tuning for Multimodal Sentiment Analysis
Authors: Mu Jie , Wang Wei , Liu Wenqi , Yan Tiantian , Wang Guanglu
Published: December 2024

Multimodal sentiment analysis has become a popular research topic in recent years. However, existing methods have two unaddressed limitations: (1) they use limited supervised labels to train models, which makes it impossible for model to fully learn sentiments in different modal data; (2) they employ text and image pre-trained models trained in different unimodal tasks to extract different modal features, so that the extracted features cannot take into account the interactive information between image and text. To solve these problems, in this paper we propose a Vision-Language Contrastive Learning network (VLCLNet). First, we introduce a pre-trained Large Language Model (LLM), which is trained from vast quantities of multimodal data, has better understanding ability for image and text contents, thus being effectively applied to different tasks while requiring few amount of labelled training data. Second, we adapt a Multimodal Large Language Model (MLLM), BLIP-2 (Bootstrapping Language-Image Pre-training) network, to extract multimodal fusion feature. Such MLLM can fully consider the correlation between images and texts when extracting features. In addition, due to the discrepancy between the pre-training task and the sentiment analysis task, the pre-trained model will output the suboptimal prediction results. We use LoRA (Low-Rank Adaptation) fine-tuning strategy to update the model parameters on sentiment analysis task, which avoids the issue of inconsistent task between pre-training task and downstream task. Experiments verify that the proposed VLCLNet is superior to other strong baselines.
Targeted Circulating Lipid Mediators and Immune Cell Gene Transcripts After ST-Elevation Myocardial Infarction
Authors: Lee Dae Hyun , Upadhyay Gunjan , Gowda Siddabasave Gowda B. , Kain Vasundhara , Malek MD Abdul , Carris Nicholas , Vasaiwala Samip , Yeatman Timothy , Oliveira Guilherme , Hui Shu-Ping , Halade Ganesh V
Published: December 2024

Residual inflammation drives atherogenesis to atherosclerosis and myocardial infarction, which triggers acute inflammation. In preclinical studies, polyunsaturated fatty acids-derived specialized pro-resolving mediators (SPMs) have been shown to promote recovery after MI, in contrast to pro-inflammatory lipid mediators (PIMs). However, the dynamic changes of lipid mediators after ST-elevation myocardial infarction (STEMI), particularly after percutaneous coronary intervention (PCI) and respective gene transcripts, are poorly understood. Therefore, the study aimed to assess the early dynamic changes in circulating lipid mediators and lipid pathway transcripts in STEMI patients who undergo PCI. In this prospective observational clinical study, patients with STEMI (n=10) and control subjects (n=6) were included. Plasma samples for lipid mediator profiling (targeted oxylipids) and whole blood for inflammation-related transcript expression were collected at baseline before PCI, 2 hours, and 24 hours post-PCI. A total of 10 STEMI patients received PCI with a mean age of 53.3 years, 90% male. Linoleic acid and DPA levels were higher in STEMI patients. A subset of PIM levels (HETEs, PGE2) were elevated at the baseline, with a subsequent decrease in circulating levels at 2 hours after PCI (TXB2, LTB4, 20-OH-LTB4). A subset of SPM levels (HEPEs) were elevated at the baseline of STEMI suggestive overlap of inflammation-resolution signaling. The temporal kinetics of LMs showed that both the initiation of inflammation and the resolution process start simultaneously and continue as an endogenous repair mechanism during STEMI. Therefore, approaches to increase these endogenous bioactive resolution mediators content and/or efficacy before PCI should be considered in treating MI patients.
MicroRNA in pediatric pulmonary hypertension microRNA profiling to inform disease classification, severity, and treatment response in pediatric pulmonary hypertension
Authors: Smith Michael A. , Chiacchia Sam , Boehme Jason , Datar Sanjeev A. , Morell Emily , Keller Roberta L. , Romer Amy , Colglazier Elizabeth , Parker Claire , Becerra Jasmine , Fineman Jeffrey R.
Published: December 2024

We present novel insight into the circulating microRNA profiles of pediatric patients with pulmonary hypertension. Our findings support the utility of microRNAs as both useful biomarkers of disease severity and potential therapeutic targets in pediatric pulmonary hypertension.
Lack of renoprotective effects by long-term PCSK9 and SGLT2 inhibition using alirocumab and empagliflozin in obese ZSF1 rats
Authors: Hummelgaard Sandra , Hvid Henning , Birn Henrik , Glerup Simon , Tom Nikola , Bilgin Mesut , Kirchhoff Jeppe Egedal , Weyer Kathrin
Published: December 2024

New treatments to slow kidney disease progression and reduce cardiovascular disease risk are needed for chronic kidney disease (CKD). We investigated the cholesterol-lowering PCSK9 inhibitor alirocumab as a new treatment for proteinuric CKD and the effect of SGLT2 inhibition using empagliflozin in obese ZSF1 rats. Regarding renoprotection, our findings were contradictory with previous preclinical studies and clinical data, suggesting that different pathophysiological mechanisms may apply to this rat model.
Soluble (pro)renin receptor as a novel regulator of renal medullary Na+ reabsorption
Authors: Yang Tianxin , Gao Zhong-Xiuzi , Mao Zi-Hui , Wu Peng
Published: December 2024

Epithelial sodium channel (ENaC) represents a major route of Na+ reabsorption in the aldosterone-sensitive distal nephron where the bulk of ENaC activity is considered to occur in the cortical collecting duct (CCD). Relatively, ENaC activity in the medulla, especially the inner medulla, is often neglected. (Pro)renin receptor (PRR), also termed ATP6ap2, a newly characterized member of the renin-angiotensin system, has emerged as an important regulator of ENaC in the distal nephron. The ENaC regulatory action of PRR is largely mediated by the 28 kDa soluble PRR (sPRR). Although all three subunits of ENaC are under the control of aldosterone, sPRR only mediates the upregulation of α-ENaC but not the other two subunits. Furthermore, sPRR-dependent regulation of α-ENaC only occurs in the renal inner medulla but not in the cortex. sPRR also rapidly upregulates ENaC activity via Nox4-derived H2O2. Overall, sPRR has emerged as an important regulator of renal medullary Na+ reabsorption in the context of overactivation of the renin-angiotensin-aldosterone system.
Exosomes derived from TREM-2 knocked-out macrophages alleviated renal fibrosis via HSPa1b/AKT pathway
Authors: Xiao Zihao , Wang Yajie , Chen Yuye , Jin Ling , Shi Yuanhui , Liu Can , Fu Cong , Cao Yuhan
Published: December 2024

Renal fibrosis is a common pathological feature of CKD, resulting in irreversible loss of function and structure. However, effective therapies for CKD are currently limited. We found that the deletion of TREM-2 in macrophages increased the MMP-9/TIMP-1 ratio in exosomes, shifting toward the degradation of the extracellular matrix (ECM) and the alleviation of renal fibrosis. Furthermore, polyclonal antibodies against TREM-2 effectively suppressed renal fibrosis. These findings provide evidence that TREM-2 is a potential therapeutic target for CKD.
Tcf21 as a founder transcription factor in specifying Foxd1 cells to the juxtaglomerular cell lineage
Authors: Anjum Hina , Smith Jason P. , Martini Alexandre G. , Yacu George S. , Medrano Silvia , Gomez R. Ariel , Sequeira-Lopez Maria Luisa S. , Quaggin Susan E. , Finer Gal
Published: December 2024

This manuscript provides novel insights into the role of Tcf21 in the differentiation of Foxd1+ cells into JG cells. Using integrated scRNA-seq and scATAC-seq, the study reveals that Tcf21 expression is crucial during early embryonic stages, with its peak at embryonic day 12. The findings demonstrate that inactivation of Tcf21 leads to fewer renin-positive areas and altered renal arterial morphology, underscoring the importance of Tcf21 in the specification of renin-expressing JG cells and kidney development.
Improving localization and measurements of M-waves using high-density surface electromyography
Authors: Bedoy Ernesto H. , Guirola Diaz Efrain A. , Dalrymple Ashley N. , Levy Isaiah , Hyatt Thomas , Griffin Darcy M. , Wittenberg George F. , Weber Douglas J.
Published: December 2024

This study introduces an innovative approach to enhancing evoked potential measurements using high-density surface electromyography (HD-sEMG). The precision and localization of evoked potentials are significantly improved by spatial filters and ultrasound imaging, offering a novel method for better assessing motor pathway integrity. These advancements could lead to more accurate tools for detecting and treating neurological deficits, making it a significant contribution to neurophysiological research.
Neurophysiological effects of latent trigger point dry needling on spinal reflexes
Authors: Seif Gretchen , Phipps Alan M. , Donnelly Joseph M. , Dellenbach Blair H. S. , Thompson Aiko K.
Published: December 2024

In this study, we examined the effects of deep dry needling (DDN) on spinal reflexes in the triceps surae. We found that the H reflex (an excitatory reflex) did not change after DDN but soleus inhibition was increased immediately and 72 h after DDN, corresponding to increases in ankle range of motion. Differential effects of DDN on excitatory and inhibitory reflexes over the first 72 h may reflect its complex neurophysiological effects at the spinal level.
Clinical Characteristics and Prognostic Factors of COVID‐19 Patients Admitted to the National Treatment Center in The Gambia
Authors: Bittaye Sheikh Omar , Jagne Abubacarr , Iddrisu Abdul-Karim , Njie Ramou , Jaiteh Lamin ES , Nyan Ousman , Jobe Ya Fatou BM , Joof Sidat , Joof Sohna , Danso Morrikebba , Bah Ebrima , Cham Musa , Roberts Charles , Bittaye Mustapha
Published: December 2024

Background and Aims: Information regarding the clinical features and outcomes of severely ill COVID‐19 patients in low‐resource settings is limited. The objective of this study was to evaluate the clinical characteristics, comorbidities, and prognostic factors associated with mortality and COVID‐19 severity among COVID‐19 patients admitted to the national COVID‐19 treatment center in The Gambia.

Methods: We conducted a retrospective cross‐sectional study on 930 confirmed COVID‐19 patients admitted to The Gambia’s national COVID‐19 treatment center from March 17, 2020, to March 13, 2023. We assessed the association between patients’ characteristics using the t‐test and the chi‐square test. Prognostic factors of mortality and COVID‐19 severity were investigated using a multivariable logistic regression model. Statistical analyses were performed using the STATA/SE 12.1 statistics/data analysis.

Results: Patients with COVID‐19 who had a saturation of peripheral oxygen (SPO2) level below 90 (severe COVID‐19) faced a fivefold higher risk of death (adjusted odds ratio [aOR] = 5.15; 95% confidence interval [CI] = 1.08, 24.58; p = 0.040). Additionally, individuals aged 60 years and older had an approximately threefold higher risk of experiencing severe COVID‐19 (aOR = 3.43; 95% CI = 2.30, 5.13; p  < 0.001), while those with comorbidities showed a 60% higher risk of severe disease (aOR = 1.60; 95% CI = 1.07, 2.38; p = 0.021).

Conclusion: These findings underscore the importance of early detection and management strategies targeting older patients and those with underlying health conditions to mitigate the impact of COVID‐19 and improve patient outcomes. Future efforts should prioritize tailored interventions and supportive care for these high‐risk populations.
A Long Way From Home: A Rare Case of Cutaneous Metastasis to the Scalp of Hepatocellular Carcinoma
Authors: Eggiman Evan , Dodia Paarth , Dewey Jesse , Munoz-Bishop Melissa , Overton Matthew
Published: December 2024

Introduction: Cutaneous metastases of hepatocellular carcinoma (HCC) are uncommon but important to recognize for timely diagnosis and management.

Case Presentation(s): We present a case of a 70‐year‐old man with a history of HCC who developed a painless nodule on the scalp. Histopathological examination and immunohistochemistry confirmed the nodule as cutaneous metastasis of HCC. The patient had previously undergone transarterial chemoembolization and surgery for HCC, with no evidence of disease for a period before presenting with the cutaneous lesion.

Conclusion: Cutaneous metastasis of HCC is rare but signifies advanced disease. This case underscores the importance of considering cutaneous manifestations in patients with a history of HCC and highlights the need for routine follow‐up and early intervention to improve patient outcomes.
Real‐World Guselkumab Response and Drug Survival in Australian Patients With Psoriasis: Results From the Australasian Psoriasis Registry
Authors: Manuelpillai Nicholas , Armstrong Julie , Ismail Fathima Ferial , Vogrin Sara , Maranta Debra , Puig Andrea , Radulski Barbara , Kern Johannes S. , Baker Christopher S. , Foley Peter
Published: December 2024

Aims: Guselkumab’s real‐world efficacy, drug survival, and patient characteristics from the Australasian Psoriasis Registry (APR) were compared with the data from the Phase III VOYAGE 1 trial.

Methods: Data from patients with severe plaque psoriasis prescribed guselkumab through the Australian Pharmaceutical Benefits Scheme (PBS) were derived from the APR. Demographic and treatment data (including psoriasis area and severity index [PASI]) at defined timepoints from 4th September 2018 to 1st October 2022 were analyzed. The baseline was PASI at the commencement of the first biologic. APR and VOYAGE 1 data were compared using 2‐sample t‐tests and chi‐square tests. Associations between patient characteristics and drug survival/time to PASI score were assessed using Cox proportional hazards regression and Kaplan–Meier estimates.

Results: 102 patients were eligible; 87.3% (n = 89) had received prior biologic therapy versus 21.6% patients in VOYAGE 1. Overall drug survival in APR was 99.0%, 93.1%, 83.3% and 77.1% at 3, 9, 15, and 27 months, respectively. At 9 months, drug survival was 100% for bionaïve and 92.1% for bioexperienced patients. In VOYAGE 1, 91.5% continued guselkumab through Week 48 (∼11 months). In the APR, the median PASI was 24.0 (IQR: 17.9–32.2) at baseline, and 1.1 (IQR: 0–2.7) at 9 months. Absolute PASI ≤ 3 and PASI90 were attained by 73.8% and 64.8%, respectively. In VOYAGE 1, 76.3% reached PASI90 at Week 48. Bionaïve patients in the APR had longer drug survival than bioexperienced.

Conclusions: Guselkumab was efficacious in the real‐world treatment of psoriasis, consistent with RCT results. Drug retention rates were high through 27 months, despite a higher proportion of bioexperienced patients in the APR than in VOYAGE 1.
Fractional Pseudospectral Schemes With Applications to Fractional Optimal Control Problems
Authors: Sahabi M. , Yazdani Cherati A.
Published: December 2024

This research endeavors to introduce novel fractional pseudospectral methodologies tailored for addressing fractional optimal control problems encompassing inequality constraints and boundary conditions. Leveraging fractional Lagrange interpolation functions, we formulate differential and integral pseudospectral matrices pivotal in discretizing fractional optimal control problems. The stability of these matrices is ensured through the utilization of Müntz–Legendre polynomials. Discretization of fractional optimal control problems entails employing integral and differential fractional matrices, with collocation strategically positioned at both Gauss and flipped Radau‐type points. Our results demonstrate that the proposed method is well suited for practical problems with larger domains. Furthermore, it proves effective for Bang‐Bang type problems and offers substantial benefits for problems with nonsmooth solutions. Comprehensive numerical evaluations on benchmark fractional optimal control problems substantiate the effectiveness of the devised pseudospectral methodologies, showcasing their commendable performance and potential for practical applications.
FDA Approval Summary: Nadofaragene Firadenovec-vncg for Bacillus Calmette–Guérin–Unresponsive Non–Muscle-Invasive Bladder Cancer
Authors: Colbert Laronna , Jia Yuxia , Sharma Anurag , Hu Jiang , Xu Zhenzhen , Suzman Daniel L. , Das Asha , Bross Peter , Kluetz Paul G. , Fashoyin-Aje Lola A.
Published: December 2024

On December 16, 2022, the FDA approved the adenoviral vector–based gene therapy nadofaragene firadenovec-vncg (brand name Adstiladrin) for the treatment of adult patients with high-risk Bacillus Calmette–Guérin (BCG)-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). The product represents the first approved adenoviral vector–based gene therapy and the first approved gene therapy for bladder cancer. Determination of efficacy was based on results from Study rAd-IFN-CS-003 (Study CS-003), a single-arm trial in 98 evaluable patients with BCG-unresponsive NMIBC with CIS who received intravesical instillations of the gene therapy product (75 mL of nadofaragene firadenovec at 3 × 1011 viral particles per mL) once every 3 months. The major efficacy outcome measures were complete response (CR) at any time and duration of response. Fifty subjects experienced CR 3 months after the initial treatment (CR = 51%; 95% confidence interval, 40.7; 61.3%), of whom 46% remained in response for ≥12 months. The median duration of response was 9.7 months (range: 3–52+). Common adverse reactions included instillation site discharge, fatigue, bladder spasm, micturition urgency, hematuria, chills, pyrexia, and dysuria. The approval of nadofaragene firadenovec provides a new therapy option for patients with BCG-unresponsive NMIBC with CIS who are ineligible for cystectomy.
Liver X Receptors and Inflammatory-Induced C/EBPβ Selectively Cooperate to Control CD38 Transcription
Authors: Glaría Estibaliz , Martínez Pol Rodríguez , Font-Díaz Joan , De la Rosa Juan Vladimir , Castrillo Antonio , Crawshaw Dylan J. , Vidal Taboada Jose Manuel , Saura Josep , Matalonga Jonathan , Nunes Chini Eduardo , Caelles Carme , Valledor Annabel F.
Published: December 2024

Introduction: Macrophages abundantly express liver X receptors (LXRs), which are ligand-dependent transcription factors and sensors of several cholesterol metabolites. In response to agonists, LXRs promote the expression of key lipid homeostasis regulators. Cross talk between LXRs and inflammatory signals exists in a cell type- and gene-specific manner. A common feature in the macrophage response to inflammatory mediators is the induction of CCAAT/enhancer-binding protein beta (C/EBPβ), a master transcriptional regulator and lineage-determining transcription factor in monocytes/macrophages. Methods: Quantitative real-time PCR in control and C/EBPβ-deficient macrophages was used to explore the role of C/EBPβ in the cross talk between inflammatory mediators and the macrophage response to pharmacological LXR activation. The functional interaction between C/EBPβ and LXRs on selected genomic regions was further characterized by chromatin-immunoprecipitation (ChIP) and gene reporter studies. Results: Whereas inflammatory signaling repressed several LXR-regulated genes involved in lipid metabolism, these effects were conserved after deletion of C/EBPβ. In contrast, inflammatory mediators and LXRs synergistically induced the expression of the multifunctional protein CD38 in a C/EBPβ-dependent manner. C/EBPβ and LXRs bound to several regions with enhancer activity upstream and within the mouse Cd38 gene and their functional cooperation in macrophages required intact binding sites for LXR and C/EBPβ. Conclusion: This study reveals positive cross talk between C/EBPβ and LXRs during the macrophage inflammatory response, which selectively impacts CD38 expression.
Macrophage Ferroptotic Resistance Is Required for the Progression of Infantile Hemangioma
Authors: Liu Jingjing , Zhong Wenqun , Wang Rong , Wang Peipei , Tong Guoyong , Chai Maosheng , Sun Yu , Zhu Tianshuang , Huang Congfa , Yang Shaodong , Zhou Xiaoshun , Mou Dongsheng , Cai Yu
Published: December 2024

Background

Ferroptosis is a programmed cell death caused by iron‐dependent accumulation and cellular lipid peroxides, which is different from apoptosis and pyroptosis. This study investigated the possible effect of ferroptotic response in the pathogenesis of infantile hemangioma (IH).

Methods and Results

The staining level of 4‐hydroxynonenal (4‐HNE), the marker of ferroptotic cells, was significantly increased in the involutive IH samples compared with the proliferative samples (9 proliferative versus 12 involutive lesions,
P
=0.0152). By contrast, the expression of glutathione peroxidase 4 (GPX4), a key enzyme regulating ferroptotic resistance, was significantly increased in the involutive IH samples. Meanwhile, the GPX4 was richly expressed in macrophages of IH. The data from in vitro study showed that the mRNA (
P
=0.0002) and protein (
P
=0.0385) expression levels of GPX4 were significantly upregulated in macrophages cultured with hemangioma‐derived stem cells conditional medium (HemSC‐CM). Mechanistically, HemSC‐CM promoted the expression of GPX4 in macrophages (
P
=0.0482) by increasing nuclear factor erythroid 2‐related factor 2 translocation to the nucleus (
P
=0.0026). Additionally, inhibition of GPX4 or inducing ferroptosis in macrophages could inhibit progression of lesion in IH nude mice mode.

CONCLUSIONS

Hemangioma‐derived stem cells (HemSCs) could promote macrophage ferroptotic resistance through upregulating expression of GPX4, which is required for the progression of IH.
Hemodynamic Characteristics and Prognostic Implication of Modified Society for Cardiovascular Angiography and Interventions Shock Classification in Comatose Patients With Out‐of‐Hospital Cardiac Arrest
Authors: Linde Louise , Beske Rasmus P. , Meyer Martin A. S. , Mølstrøm Simon , Grand Johannes , Helgestad Ole K. L. , Ravn Hanne B. , Schmidt Henrik , Kjærgaard Jesper , Hassager Christian , Møller Jacob E.
Published: December 2024

Background

Cardiogenic shock complicating acute myocardial infarction is associated with a high mortality rate. Cardiogenic shock after out‐of‐hospital cardiac arrest (OHCA) can be due to transient myocardial stunning but also reflect the increasing severity of ongoing heart failure. The Society for Cardiovascular Angiography and Interventions (SCAI) proposed a division of cardiogenic shock into 5 phenotypes, with cardiac arrest being a modifier. The objective was to apply SCAI shock classification to a well‐characterized OHCA population and describe the hemodynamic characteristics and prognostic significance of increasing SCAI classes.

Methods and Results

This is a post hoc analysis of data from the BOX (Blood Pressure and Oxygenation Targets in Post Resuscitation Care) trial of comatose patients with OHCA. Patients were classified according to SCAI class upon hospital admission. Invasive arterial and pulmonary arterial measurements were obtained the first 72 hours after admission, and perfusion pressure, cardiac index and cardiac power output were calculated. Of 789 patients included, 31.6% were classified as SCAI class B/C, 29.9% as SCAI class D, and 38.5% as SCAI class E. The first recorded perfusion pressure differed between SCAI class B/C, D, and E being lower in higher SCAI classes. The difference was found only at the first measurement. Cardiac index and cardiac power output did not differ at any time point between classes. The 1‐year mortality rate increased with SCAI Class B/C to E (21.3%, 34.3%, and 48.4%, respectively;
P
<0.001).

Conclusions

The 1‐year mortality rate after OHCA increased with increasing SCAI classes, but cardiac index, cardiac power output, and perfusion pressure remained notably similar in the first 72 hours after admission. This challenges whether all OHCAs should be recorded as SCAI class E by default.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03141099.
Safety and Efficacy of Intravenous Thrombolysis by Infarct Type in Patients with No Visible Occlusion: A Secondary Analysis of the AcT Trial
Authors: Siddiqi A. Zohaib , Ignacio Katrina , Kaveeta Chitapa , Bala Fouzi , Ademola Ayoola , Tkach Aleksander , Buck Brian H. , Catanese Luciana , Hunter Gary , Dowlatshahi Dar , Shamy Michel , Zafar Atif , Field Thalia S. , Appireddy Ramana , Wadhwa Ankur , Sajobi Tolulope , Swartz Rick , Almekhlafi Mohammed , Demchuk Andrew , Menon Bijoy , Singh Nishita
Published: December 2024

Background

About 25% of patients with acute ischemic stroke have lacunar infarct on follow‐up imaging. In this secondary analysis from the AcT (Alteplase Compared With Tenecteplase) trial, we assessed if there is variation in safety or efficacy of intravenous thrombolysis by infarct type in patients with no visible occlusion. We also determined if this effect differed between tenecteplase and alteplase.

Methods and Results

This is a secondary analysis from the AcT trial. Lacunar infarct was defined as single, ≤15 mm, and in regions supplied by perforating arterioles on 24‐hour imaging. Outcomes included symptomatic intracerebral hemorrhage at 24 hours, any hemorrhage on imaging, and 90‐day modified Rankin Scale score. Mixed‐effects regression models adjusted for age, sex, stroke severity, thrombolytic type, and onset‐to‐needle time were used. Of 1577 patients, 456/29.9% had no visible occlusion and interpretable follow‐up imaging (magnetic resonance imaging: 41.2%). Of these 93 (20.4%) (magnetic resonance imaging: 62.3%) had lacunar infarct, 171 (37.5%) (magnetic resonance imaging: 67.4%) had nonlacunar infarct, and 192 (42.1%) (magnetic resonance imaging: 7.3%) had no visible infarct. Four patients (2.3%) in the group with nonlacunar infarct and none in the groups with lacunar infarct and no visible infarct developed symptomatic intracerebral hemorrhage. Any intracranial hemorrhage was highest (21; 12.4%) in the group with nonlacunar infarct. There was no significant interaction between thrombolytic type and treatment outcomes.

Conclusions

In the AcT trial, safety of intravenous thrombolysis was similar across all infarct types in patients with no visible occlusion but functional outcomes were worst in patients with nonlacunar infarct. Safety and functional outcomes after intravenous thrombolysis were better in the groups with lacunar infarct and no visible infarct as compared with the overall trial population.
Myocardial Infarction Injury Is Exacerbated by Nicotine in Vape Aerosol Exposure
Authors: Savko Clarissa , Esquer Carolina , Molinaro Claudia , Rokaw Sophie , Shain Abraham G. , Jaafar Faid , Wright Morgan K. , Phillips Joy A. , Hopkins Tyler , Mikhail Sama , Rieder Abigail , Mardani Ariana , Bailey Barbara , Sussman Mark A.
Published: December 2024

Background

Vaping is touted as a safer alternative to traditional cigarette smoking, but the full spectrum of harm reduction versus comparable risk remains unresolved. Elevated bioavailability of nicotine in vape aerosol together with known risks of nicotine exposure may result in previously uncharacterized cardiovascular consequences of vaping. The objective of this study is to assess the impact of nicotine exposure via vape aerosol inhalation upon myocardial response to infarction injury.

Methods and Results

Flavored vape juice containing nicotine (5 mg/mL) or vehicle alone (0 mg) was delivered using identical 4‐week treatment protocols. Mice were subjected to acute myocardial infarction injury and evaluated for outcomes of cardiac structure and function. Findings reveal that nicotine exposure leads to worse outcomes with respect to contractile performance regardless of sex. Nonmyocyte interstitial cell accumulation following infarction significantly increased with exposure to vape aerosol alone, but a comparable increase was not present when nicotine was included.

Conclusions

Myocardial function after infarction is significantly decreased after exposure to nicotine vape aerosol irrespective of sex. Comparable loss of contractile function was not observed in mice exposed to vape aerosol alone, highlighting the essential role of nicotine in loss of contractile function. Increased vimentin immunoreactivity was observed in the vape alone group compared with control and vape nicotine. The correlation between vaping, interstitial cell responses, and cardiac remodeling leading to impaired contractility warrants further investigation. Public health experts seeking to reduce vaping‐related health risks should consider messaging that highlights the increased cardiovascular risk especially with nicotine‐containing aerosols.
Adaptive Platform Trials in Stroke
Authors: Lorenzi Elizabeth , Crawford Amy M. , Anderson Craig S. , Menon Bijoy , Chen Xiaoying , Mistry Eva , Khatri Pooja , Elm Jordan J. , Beall Jonathan , Saville Benjamin R. , Berry Scott M. , Lewis Roger J.
Published: December 2024

Clinical trials of treatments for stroke have generally utilized 2-arm, randomized designs to evaluate a single intervention against a control. Running separate clinical trials, with each addressing a single therapeutic question, is resource intensive and slows evidence generation, especially in a field with rapidly expanding treatment options and evolving practices. Platform trials—randomized clinical trials designed to evaluate multiple interventions that may enter and exit the ongoing platform based on a master protocol—accelerate the investigation of multiple therapeutic options within a single infrastructure. This in turn has the potential to accelerate access to new interventions for patients with stroke that can save lives and improve outcomes. In the context of acute ischemic stroke, 2 new platform trials have been established, the STEP trial (StrokeNet Thrombectomy Endovascular Platform) and ACT-GLOBAL (A Multi-Factorial, Multi-Arm, Multi-Stage, Randomised, Global Adaptive Platform Trial for Stroke), to address multiple therapeutic questions simultaneously using a multifactorial design including Bayesian modeling and other adaptive features. These trials are designed to maximize the information obtained from each participant, to align clinical research more closely with the complexities of clinical care, and to accelerate the identification of effective therapies. This article explores conceptual, practical, and statistical considerations in the design and implementation of adaptive platform trials and highlights their potential to accelerate the identification of new therapies, management, and rehabilitation in stroke.
Transcranial Cortex-Wide Imaging of Murine Ischemic Perfusion With Large-Field Multifocal Illumination Microscopy
Authors: Chen Zhenyue , Zhou Quanyu , Droux Jeanne , Liu Yu-Hang , Glück Chaim , Gezginer Irmak , Wyss Matthias , Yoshihara Hikari A.I. , Kindler Diana Rita , Weber Bruno , Wegener Susanne , El Amki Mohamad , Razansky Daniel
Published: December 2024

BACKGROUND:

Ischemic stroke is a common cause of death worldwide and a main cause of morbidity. Presently, laser speckle contrast imaging, x-ray computed tomography, and magnetic resonance imaging are the mainstay for stroke diagnosis and therapeutic monitoring in preclinical studies. These modalities are often limited in terms of their ability to map brain perfusion with sufficient spatial and temporal resolution, thus calling for development of new brain perfusion techniques featuring rapid imaging speed, cost-effectiveness, and ease of use.

METHODS:

We report on a new preclinical high-resolution angiography technique for murine ischemic stroke imaging based on large-field high-speed multifocal illumination fluorescence microscopy. We subsequently showcase the proposed method by monitoring therapeutic effects of thrombolysis in stroke (n=6), further performing cross-strain comparison of perfusion dynamics (n=6) and monitoring the therapeutic effects of sensory stimulation–based treatment (n=11).

RESULTS:

Quantitative readings of hemodynamic and structural changes in cerebral vascular network and pial vessels were attained with 14.4-µm spatial resolution at 80-Hz frame rate fully transcranially. The in vivo perfusion maps accurately delineated the ischemic core and penumbra, further exhibiting a strong correlation (86.1±4.5%) with ex vivo triphenyl tetrazolium chloride staining, significantly higher than for the conventional laser speckle contrast imaging method. Monitoring of therapeutic effects of thrombolysis confirmed that early recanalization could effectively save the penumbra while reducing the infarct area. Cross-strain comparison of perfusion dynamics affirmed that C57BL/6 mice feature a larger penumbra and smaller infarct core as compared with BALB/c mice, which have few or no collaterals. Sensory stimulation–based treatment could effectively enhance blood flow and abolish perfusion deficits in the ischemic core and penumbra regions.

CONCLUSIONS:

A high-speed fluorescence-based angiography method for transcranial stroke imaging in mice is introduced, which is capable of localizing brain perfusion changes and accurately assessing the ischemic penumbra. Compared with the whole-brain x-ray computed tomography and magnetic resonance imaging methods, which are conventionally used for stroke diagnosis and therapeutic monitoring, the new approach is simple and cost-effective, further offering high resolution and speed for in vivo studies. It thus opens new venues for brain perfusion research under various disease conditions such as stroke, neurodegeneration, or epileptic seizures.
Climata et temperamenta: the Influence of Climate and Environment on Human Complexion in the Thirteenth and Fourteenth Centuries
Authors: Miteva Evelina
Published: December 2024

The present paper addresses the way in which local conditions – geographical, biological or astrological – were believed to influence the general constitution of human nature from the viewpoint of natural philosophy. What were the material conditions that constituted the diversity between peoples and individuals? The focus of this paper is on the relation between climatic zones and the complexion of their inhabitants. This relation and the ensuing natural determinism are present in Albert the Great’s De natura loci. While not being as specific as Albert in laying out the ethnographic specifics, Thomas Aquinas shared the general framework set out by his teacher that astrological and geographical conditions greatly affect the complexion of the inhabitants. In his unedited commentary on Aristotle’s Parva naturalia, John Buridan sticks to the general Aristotelian paradigm, to which Albert and Thomas also adhered, but considers in greater detail the way climatic conditions affect the individual human complexion.
Observations on the Verb Morphology of the Language of the “Amorite-Akkadian Bilinguals”
Authors: Arkhipov Ilya , Loesov Sergey
Published: December 2024

The left column of the newly published “Amorite-Akkadian bilinguals” contains words and sentences in a heretofore unknown Northwest Semitic language, with an Old Babylonian translation. The present study compares the verb morphology of this language with those of Biblical Hebrew and various Aramaic languages.
Conversion Narratives as Mirrors of Religious Encounters
Authors: Bornet Philippe
Published: December 2024

This article focuses on the narratives that emerged from two conversion episodes in Kerala in the 1920s involving the German missionary Paul Sengle (1870–1932): the conversion of a young Hindu woman named Kalyani and attempts to convert members of the Ezhava caste amid competition from Hindus, Muslims, and Buddhists. While mainly drawing on materials produced by the Basel Mission or by missionaries in the field like Sengle, this article also gives space to the perspectives of the newly converted person and of the rival religious communities. It suggests studying conversion experiences as shaped by situations of interaction, by connecting sources that represent the divergent perspectives of all the parties involved in such cases. This approach helps to examine the different sides of a conversion experience at both macro and micro levels and offers insights into the broader processes of religious encounters in the early twentieth century global history of religions.
Black History in the Chinese Imagination: From Maoist Revolution to Deng Xiaoping’s Reforms, 1964–1989
Authors: Barnes Melvin
Published: December 2024

This article examines Chinese interpretations of the Black experience in the United States and maps its evolution from 1964 to 1989. It argues that the transition of the People’s Republic of China (prc) from a revolutionary socialist state under Mao Zedong in the 1960s to a socialist state focused on implementing Deng Xiaoping’s socioeconomic reforms in the 1980s necessitated a reimaging of the prc’s engagement with African Americans. Western literature on the prc’s engagement with African Americans has focused primarily on Mao’s China between 1949 and 1976. The aim of this article is to examine Chinese engagement with Black history and African Americans into the Reform Era to contribute to this body of literature. By bridging the 1976 divide, it offers a novel interpretation that demonstrates how accelerated international exchanges and the prc’s domestic reforms defined Sino-African American engagement.
Advocating for the Civil Rights of Japanese Americans at the Incarceration Camps
Authors: Iwai Shuma
Published: December 2024

Galen Merriam Fisher was one of the few White American activists protesting for the civil rights of Japanese Americans during World War ii. Japan’s attack on Pearl Harbor brought the United States into World War ii in December 1941. Prioritizing national security, President Franklin D. Roosevelt issued the Executive Order 9066 in February 1942. It called for the exile of Japanese Americans to incarceration camps without trials or hearings, where they experienced racial discrimination, prejudice, and unequal treatment. This article examines Fisher’s activism on behalf of Japanese Americans. As a former long-time missionary in Japan, he consistently voiced his concerns about maltreatment of Japanese Americans to the U.S. federal authorities and the public. While offering detailed historical context, this study carefully analyzes Fisher’s arguments about the violation of constitutional rights, harsh treatment, and racial discrimination at the camps, and for early release of Japanese Americans. It will support historians, Asianists, and scholars of Asian American studies because it offers a model to advocate against injustices and for civil rights, which one can apply to other similar historical and/or current contexts.