bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymptotic-preserving finite element analysis of Westervelt-type wave equations
Authors: Nikolić Vanja
Published: November 2024

Motivated by numerical modeling of ultrasound waves, we investigate conforming finite element approximations of quasilinear and possibly nonlocal equations of Westervelt type. These wave equations involve either a strong dissipation or damping of fractional-derivative type and we unify them into one class by introducing a memory kernel that satisfies non-restrictive regularity and positivity assumptions. As the involved damping parameter is relatively small and can become negligible in certain (inviscid) media, it is important to develop methods that remain stable as the said parameter vanishes. To this end, the contributions of this work are two-fold. First, we determine sufficient conditions under which conforming finite element discretizations of (non)local Westervelt equations can be made robust with respect to the dissipation parameter. Second, we establish the rate of convergence of the semi-discrete solutions in the singular vanishing dissipation limit. The analysis hinges upon devising appropriate energy functionals for the semi-discrete solutions that remain uniformly bounded with respect to the damping parameter. Numerical experiments are provided to illustrate the theory.
Barrier coverage construction without barrier-breach using virtual lines
Authors: Lee Joong-Lyul , Su Ke , Zhou Yisheng
Published: November 2024

In wireless sensor networks (WSNs), barrier coverage is used to detect objects crossing a protected area or to monitor an area of interest. It is a critical application within WSNs. Due to cost considerations, sensor nodes are often randomly deployed along the boundary of the monitoring area, constructing multiple barriers to maximize network lifetime. These barriers operate based on a sleep-wakeup schedule. However, a new security issue, known as the barrier-breach problem, can arise during this schedule. In this paper, we propose a novel barrier coverage construction algorithm (BCC_VL) that addresses the barrier-breach problem using Virtual Lines (VLs), a concept that has not been explored before. By employing VLs, our algorithm can construct a barrier coverage without any breaches. We conducted simulations to validate the proposed method, and the results were compared and verified against the MaxFlow model. In the MaxFlow_RM method, our approach demonstrated superior performance in identifying barrier coverage.
A Moving Mesh Method for Fluid-Solid-Acoustic Interactions in MEMS Devices
Authors: Mayrhofer Dominik , Roppert Klaus , Tumpold David , Kaltenbacher Manfred
Published: November 2024

In multi-physical investigations, modeling moving objects at the micro-scale often requires the inclusion of mesh movement and viscous losses due to boundary layers. State-of-the-art approaches use, for example, the full set of flow equations. However, these equations are more computationally expensive due to their non-linearity. Here, we present a formulation for efficiently modeling visco-acoustic propagation problems on moving domains combined with fluid-solid-acoustic interaction. Therefore, we apply the Arbitrary-Lagrangian-Eulerian (ALE) framework to the fully linearized flow equations for a Newtonian fluid. Neglecting the non-linearity means that no sub-iterations during the solving process are necessary compared to the full set of flow equations. For the mesh deformation, we utilize a quasi-static mechanical field which is iteratively coupled to the flow equations in a strong sense. Furthermore, we use non-conforming interfaces to couple the acoustic and flow fields directly. The formulation presented is verified through convergence studies, proving second-order convergence using Taylor-Hood elements. Finally, the formulation is applied to model a Micro-Electro-Mechanical-System (MEMS) loudspeaker unit cell useable for ultrasound-based pumping principles like Advanced Digital Sound Reconstruction (ADSR). In summary, this formulation can efficiently model acoustic propagation problems of moving objects at the micro-scale.
Efficient Solution Strategies for Cabin Noise Assessment of Wave-Resolving Aircraft Fuselage Models
Authors: Blech Christopher , Sreekumar Harikrishnan K. , Hüpel Yannik , Langer Sabine C.
Published: November 2024

For the purpose of high-fidelity aircraft cabin noise simulations during early design phases, we examine three efficient solving approaches for the fully coupled finite element model of an aircraft fuselage segment. Obtaining an efficient solution with respect to consumed computational time and resources is challenging within a conventional simulation pipeline, as large-scale and complex vibroacoustic models demand crucially high computational costs with increasing frequency. In this contribution, we adopt (1) frequency and domain specific discretization, (2) domain-decomposition techniques, and (3) model order reduction with rational Arnoldi Krylov subspace methods for an aircraft fuselage model. The three approaches have shown remarkable advantage thereby reducing the solving time as well as the memory requirement that are essential when solving large-scale models. While the discretization and the model order reduction approaches accelerate the solving process by efficiently handling the complexity of the system to be solved, domain-decomposition techniques further handle the aspect of reducing the overall memory consumption. Finally with the help of active research aircraft segment models, we implement and showcase the achieved efficiency.
Democratizing Container Live Migration for Enhanced Future Networks - A Survey
Authors: Soussi Wissem , Gür Gürkan , Stiller Burkhard
Published: November 2024

Emerging cloud-centric networks span from edge clouds to large-scale datacenters with shared infrastructure among multiple tenants and applications with high availability, isolation, fault tolerance, security, and energy efficiency demands. Live migration (LiMi) plays an increasingly critical role in these environments by enabling seamless application mobility covering the edge-to-cloud continuum and maintaining these requirements. This paper presents a comprehensive survey of recent advancements that democratize LiMi, making it more applicable to a broader range of scenarios and network environments both for virtual machines (VMs) and containers, and analyzes LiMi’s technical underpinnings and optimization techniques. It also delves into the issue of connections handover, presenting a taxonomy to categorize methods of traffic redirection synthesized from the existing literature. Finally, it identifies technical challenges and paves the way for future research directions in this key technology.
Mechanisms and Implications of Electrical Heterogeneity in Cardiac Function in Ischemic Heart Disease
Authors: Martinez-Navarro Hector , Zhou Xin , Rodriguez Blanca
Published: November 2024

A healthy heart shows intrinsic electrical heterogeneities that play a significant role in cardiac activation and repolarization. However, cardiac diseases may perturb the baseline electrical properties of the healthy cardiac tissue, leading to increased arrhythmic risk and compromised cardiac functions. Moreover, biological variability among patients produces a wide range of clinical symptoms, which complicates the treatment and diagnosis of cardiac diseases. Ischemic heart disease is usually caused by a partial or complete blockage of a coronary artery. The onset of the disease begins with myocardial ischemia, which can develop into myocardial infarction if it persists for an extended period. The progressive regional tissue remodeling leads to increased electrical heterogeneities, with adverse consequences on arrhythmic risk, cardiac mechanics, and mortality. This review aims to summarize the key role of electrical heterogeneities in the heart on cardiac function and diseases. Ischemic heart disease has been chosen as an example to show how adverse electrical remodeling at different stages may lead to variable manifestations in patients. For this, we have reviewed the dynamic electrophysiological and structural remodeling from the onset of acute myocardial ischemia and reperfusion to acute and chronic stages post–myocardial infarction. The arrhythmic mechanisms, patient phenotypes, risk stratification at different stages, and patient management strategies are also discussed. Finally, we provide a brief review on how computational approaches incorporate human electrophysiological heterogeneity to facilitate basic and translational research.
Diagnostic Performance of AI-enabled Plaque Quantification from Coronary CT Angiography Compared with Intravascular Ultrasound
Authors: Ihdayhid Abdul Rahman , Tzimas Georgios , Peterson Kersten , Ng Nicholas , Mirza Saba , Maehara Akiko , Safian Robert D.
Published: November 2024

Automated artificial intelligence–based quantification of coronary plaque volume from cardiac CT was highly correlated with the invasive reference standard of intravascular ultrasound.
A Hybrid Electrochemical Multi-Particle Model for Li-ion Batteries
Authors: Ali Haider Adel Ali , Raijmakers Luc H. J. , Tempel Hermann , Danilov Dmitri L. , Notten Peter H. L. , Eichel Rüdiger-A.
Published: November 2024

Physics-based models have proven to be effective tools for predicting the electrochemical behavior of Li-ion batteries. Among the various physics-based models, the Doyle-Fuller-Newman (DFN) model has emerged as the most widely employed. In response to certain limitations of the DFN model, the multiple particle-Doyle-Fuller-Newman (MP-DFN) model was introduced. The MP-DFN model utilizes multiple electrode particle sizes, addressing internal concentration heterogeneities and more realistically simulate diffusion processes in the electrodes. However, the model requires relatively high computational cost. This work introduces the Padé approximation for the MP-DFN model, resulting in the simplified MP-DFN model, leading to a faster simulation time. However, depending on battery design and operation conditions, this solution shows to have lower accuracy compared to the MP-DFN. To overcome these challenges, this study also introduces a hybrid MP-DFN model. This model uses a novel approach aimed at striking a balance between accuracy and computational speed. The hybrid MP-DFN model integrates both the finite difference method (FDM) and Padé approximation to effectively address the challenges posed by multiple particle sizes within the electrodes. The choice between FDM or the approximations for a specific particle in the electrode is determined by the scaled diffusion length.
PhysioCAFUN: a competency-based curriculum development guideline to strengthen physiology education in Africa
Authors: Alagbonsi Abdullateef Isiaka , Essop M. Faadiel , El-Wazir Yasser , Nyakudya Trevor , Fastone Goma , Mojiminiyi Frank , Saeed Amal , Stienen Ger J. M. , Balandya Emmanuel , Raji Yinusa , Bintou Sarr Fatou , Samb Abdoulaye , Ebrahim Ashabilan , Pohl Ulrich , Silverthorn Dee U.
Published: November 2024

We described the development of Physiology Curriculum for African Universities (PhysioCAFUN), a competency-based curriculum development guideline to promote physiology education in Africa. This freely accessible resource document should help African universities where there is a dearth of physiologists and thus aid in drafting a curriculum suitable for their local needs. Likewise, it should assist universities globally where physiology programs are already in place to benchmark and/or revise their curriculum as may be needed.
The landscape of undergraduate introduction to exercise science courses
Authors: Johnson Samantha , Fleming Jessica K. , Stenson Mary , Mel Astrid , Spillios Katherine , Caputo Jennifer
Published: November 2024

Although introductory courses are important gateways to the exercise science major, there is a lack of consensus on content and delivery. Among institutions across the United States, introductory class size and mode of delivery varied, as well as who could enroll in and who taught the course. Course characteristics were related to institution type and major size. Relationship building and knowledge acquisition were perceived by faculty as key benefits of introductory classes for students and programs.
Understanding Experiences of Diabetes Distress: A Systematic Review and Thematic Synthesis
Authors: Morales-Brown Louise Anne , Perez Algorta Guillermo , Salifu Yakubu
Published: November 2024

Background: Diabetes distress is a common emotional issue for those living with diabetes, which has the potential to negatively impact well‐being, management behaviors, and HbA1c levels. These implications have led to diabetes distress becoming an important consideration in diabetes healthcare and management. Nonetheless, discussions remain ongoing on how to best conceptualize this experience. Recent research has attempted to enhance conceptualization by considering the underlying emotional mechanisms that may underpin the highly contextualized experience of diabetes distress. Qualitative insights can further add to these understandings; however, the research in this remit is yet to be systematically reviewed. This review therefore sought to add to the growing body of literature attempting to better conceptualize diabetes distress and the underlying mechanisms that may contribute to this experience. A secondary aim was to leverage this understanding to consider ways to improve patient–healthcare interactions.

Methods: A qualitative systematic review and thematic synthesis was undertaken. Eligible studies were identified through PsycINFO, MEDLINE, CINAHL, and EMBASE databases from November 2020 to May 2021. Study quality was assessed using the McMaster Critical Review Form.

Results: Nineteen papers were included in the review. The analysis resulted in seven descriptive themes which contributed to three analytical themes: (1) threatened autonomy, (2) sense of helplessness, and (3) negative sense of self. These results highlight that a major area underpinning experiences of diabetes distress is not feeling in control.

Conclusions: Consideration should be given to how psychological factors, such as locus of control and learned helplessness, may constitute underlying mechanisms impacting emotional regulation in those experiencing diabetes distress. Clinicians should consider including and leading discussions around distress during appointments, as well as using approaches that promote patient autonomy and empowerment.
Methods to Estimate the Between‐Population Level Effective Reproductive Number for Infectious Disease Epidemics: Foot‐And‐Mouth Disease (FMD) in Vietnam
Authors: Gunasekera Umanga , VanderWaal Kimberly , Arzt Jonathan , Perez Andres
Published: November 2024

Foot‐and‐mouth disease (FMD), which is endemic in 77% of countries globally, is a major threat to the global livestock industry. Knowledge of the reproductive number at the population level (i.e., farm level, herd level, or above) for FMD is important to estimate the magnitude of epidemics and design and implement effective control methods. Different methods, based on disparate assumptions and limitations, have been used interchangeably to compute and report reproductive numbers at the population level without a formal comparison between them. This study compares the results obtained when using alternative methods to compute between populations (Rbp) for FMD using one single dataset collected over 10 years (2007–2017) at the commune‐level swine farms in Vietnam. Seven spatial–temporal clusters were identified in the country, and the value of Rbp was computed on each of them using different analytical approaches, namely, epidemic doubling time, nearest neighbor, time‐dependent reproductive number (TDR), sequential Bayesian (SB), and birth–death skyline (BDSKY) analysis in Bayesian evolutionary analysis by sampling trees 2 (BEAST2). Estimated Rbp values were relatively similar across methods ranging from 1.25 to 1.61. For the first time, the results here provide a comparison of different methods used to compute Rbp for FMD. Despite differences in assumptions and limitations, results suggest that different methods produce relatively similar outputs. Additionally, the results here provide foundational knowledge to support the evaluation and control of FMD epidemics in a population.
A Rare Cause of Colon Perforation After Percutaneous Nephrolithotomy—A Case Report and Review of the Literature
Authors: Boutros Christina S. , Loftus Alexander W. , Bassiri Aria , Davis Laura E. , Vince Randy , Sinopoli Jillian , Tapias Leonidas , Linden Philip A. , Towe Christopher W. , Jiang Boxiang
Published: November 2024

Staghorn calculi pose challenges in urology, often necessitating more invasive procedures such as percutaneous nephrolithotomy (PCNL) to clear a large stone burden with fewer procedures. Here we present a case of a 76‐year‐old female with chronic kidney disease and a malrotated right pelvic kidney who underwent PCNL for a 3.5 cm staghorn calculus. Postoperatively, she developed a rare complication of ascending colon perforation, requiring emergent surgical intervention including exploratory laparotomy and right hemicolectomy. Colon perforation during PCNL is rare (0.3%−0.8%). Preoperative imaging, namely computed tomography (CT) of the abdomen and pelvis, is crucial to identify anatomical variations and mitigate the risk of injury. Conservative management strategies have demonstrated success in similar cases, emphasizing the importance of prompt recognition and multidisciplinary management. This case contributes to the paucity of literature regarding this rare complication underscoring the necessity for detailed preoperative planning to avoid complications in PCNL, especially in patients with complex renal anatomy. Future research should focus on developing tailored guidelines for PCNL in patients with anatomical abnormalities to enhance procedural safety and optimize outcomes.
StreamLight Single‐Step Transepithelial Photorefractive Keratectomy (PRK) for Myopia and Myopic Astigmatism
Authors: Gunn David J. , Cox Rebecca A.
Published: November 2024

Background: To report the refractive outcomes of StreamLight transepithelial photorefractive keratectomy (PRK).

Methods: A retrospective case series was conducted which included a total of 205 eyes of 109 patients who underwent StreamLight transepithelial PRK using the Alcon Wavelight EX500 excimer laser. All eyes had myopia or myopic astigmatism, and the preoperative spherical equivalent (SEQ) ranged from −0.63D to −7.25D. The primary postoperative outcomes were UDVA, CDVA and subjective refraction measured at least 3 months postoperatively.

Results: Postoperatively, 196 eyes (95.6%) had a UDVA of 20/20 or better. The mean SEQ was −0.05 ± 0.31D and 189 eyes (92.2%) were within ±0.50D of the target SEQ. The mean refractive astigmatism was −0.28 ± 0.27D, and 181 eyes (88.3%) had ≤ 0.50D of astigmatism. The mean safety and efficacy indices were 1.01 ± 0.08 and 0.97 ± 0.12, respectively. Eight eyes lost 1 line of CDVA. Six of these were noted to have significant dry eyes and 2 had corneal haze. No eye lost two or more lines of CDVA.

Conclusions: StreamLight transepithelial PRK results in excellent refractive outcomes for myopia and myopic astigmatism.
Spatiotemporal Differences in Regional Tourism Efficiency: An Empirical Study From Guangdong Province, China
Authors: Wang Haifei
Published: November 2024

The focus on high‐quality development in regional tourism involves not only transforming the previous extensive development model and improving the efficiency of tourism development but also promoting the coordinated development of the tourism industry across different regions. Taking the 21 prefecture‐level cities in Guangdong Province as the research object and guided by high‐quality development, a tourism efficiency measurement index system that includes carbon emissions as an unexpected output has been established. By comprehensively applying methods such as the Super‐SBM model, LISA temporal path, and standard deviation ellipse, this study addresses the neglect of spatial relationships in the existing literature and measures the tourism efficiency of Guangdong’s 21 prefecture‐level administrative units from 2009 to 2019, exploring its spatiotemporal evolution and collaborative trends. The results show that during the research period, the average tourism efficiency in Guangdong Province was 0.807, at a medium–high efficiency level. Spatially, the tourism efficiency of the province is composed of a main peak and side peaks, with a general leftward shift of the main peak, a fluctuating decrease in peak height, and an expanding width. The evolution of spatial patterns reveals that regions with similar tourism efficiency in Guangdong tend to be spatially concentrated, with strong local stability and clear spatial dependency in the change process of tourism efficiency. The study’s insights suggest strategies for Guangdong’s tourism sector, advocating for technological innovation, sustainable development practices, and a robust evaluation framework. It emphasizes leveraging regional tourism assets, fostering collaboration, and promoting the “Great Lingnan Tourism Circle” for a balanced industry growth.
Neoadjuvant Chemotherapy Shortens the cfDNA Telomere Length in Breast Cancer Patients
Authors: Peker Eyüboğlu İrem , Koca Sinan , Çelik Betül , Güllü Amuran Gökçe , Uğurlu M. Ümit , Alan Özkan , Akın Telli Tuğba , Yumuk Perran Fulden , Akkiprik Mustafa
Published: November 2024

Introduction: Cancer is a genetic disease that affects people worldwide, and breast cancer is the most common cancer in women. Studies have been conducted on molecular parameters to predict tumor behavior and develop therapeutic strategies. Telomeres, which are at the end of chromosomes, have been studied for their relationship with breast cancer, but more research is needed to understand their role in the disease. Circulating‐free DNA (cfDNA) is DNA that is free in the bloodstream and is considered a promising target for early cancer detection, treatment response monitoring, and prognosis assessment. This study is aimed at comparing cfDNA telomere length of breast cancer patients and healthy individuals and analyzing the impact of neoadjuvant chemotherapy on telomere length in cfDNA.

Materials and Methods: Blood samples were collected from 33 breast cancer patients undergoing neoadjuvant chemotherapy before and after treatment. The quantitative PCR method is used to measure the average telomere lengths.

Results: This study found that the telomere length of cfDNA in breast cancer patients before and after treatment is significantly shorter than in the control group. Neoadjuvant chemotherapy is found to shorten the cfDNA telomere length, especially in the treatment‐responsive group.

Conclusion: Our study suggests that telomere length in cfDNA may be a useful biomarker for predicting therapy response and possible reoccurrence of the disease in breast cancer patients.
Treatment of Xylazine‐Associated Injection Skin Injuries
Authors: Yeung Ho-Man , Worrilow William Mills
Published: November 2024

With the introduction of fentanyl and xylazine in the drug supply market, injection‐related skin injuries and wounds are becoming more common. Xylazine is an alpha‐2 adrenergic agonist thought to cause deep ulcerative wounds due to peripheral vasoconstriction leading to poor wound healing. This case series describes four patients with injection drug use leading to severe xylazine‐related skin injuries who were treated between 2022 and 2023. This paper provides visualization of the extent and severity of these “tranq wounds,” as well as the healing progression when receiving medical treatment, addiction treatment, and wound care. Medical treatment and overall care were complicated by individual social determinants of health. Further understanding of xylazine‐related wounds is necessary as xylazine continued to be an emerging threat in the United States. Though some reports in the literature capture the appearances, only few displayed progressive improvements or success in treatment given the challenging nature of treating this high‐risk population.
A Systematic Review and Meta‐Analysis of the Efficacy of Biosecurity in Disease Prevention and Control in Livestock Farms in Africa
Authors: Ngom Ronald Vougat , Ayissi Gaspard J. , Akoussa Adonis M. M. , Laconi Andrea , Jajere Saleh M. , Zangue Henriette A. , Piccirillo Alessandra
Published: November 2024

In Africa, livestock production plays a crucial role for sustainable food security and economic growth. However, the development of this sector has been delayed by livestock diseases, one of the main constraints, which can cause important production and economic losses. To overcome these constraints, farmers extensively use antimicrobials, which in turn can lead to antimicrobial resistance (AMR), one of the main threats to global health and food security. Biosecurity has been identified as a key strategy to reduce livestock diseases. Therefore, the current systematic review and meta‐analysis, conducted according to the Cochrane guideline, aimed at determining the efficacy of biosecurity in preventing and controlling infectious diseases in livestock farms in Africa. Of the 1408 records retrieved from five different databases, only 16 met the inclusion criteria. These studies were conducted in Egypt (31.2%), Nigeria (31.2%), Uganda (18.8%), Ethiopia (12.5%) and Tunisia (6.3%) and concerned poultry (62.4%), pigs (18.8%) and cattle (18.8%). Investigations focused mainly on avian influenza (AI) (15.0%) and coccidiosis (10.0%) in poultry and African swine fever (ASF) (10.0%) in pigs. In poultry farms, the results of the pairwise meta‐analysis showed that biosecurity measures related to visitors and farmworkers could be effective at reducing the risk of introduction and spread of AI viruses (odds ratio [OR] = 0.48; 95% confidence interval [CI] 0.28–0.82). Moreover, inadequate biosecurity seemed to be a factor promoting coccidiosis (OR = 4.20; 95% CI 2.4–7.4) and AI (OR = 1.74; 95% CI 1.23–2.48). Prevention of ASF was significantly associated with the application of biosecurity measures related to animals’ transport, removal of carcasses and manure (OR = 0.33; 95% CI 0.12–0.88). Despite their importance, these findings cannot be translated to the entire African continent, since no studies were available for more than 90% of its countries. More research should be carried out to fill in the gaps identified by this review.
The Effectiveness of Problem‐Based Learning in Reducing Work‐Related Musculoskeletal Problems Among Hospital Nurses: An Interventional Study
Authors: Modarresi Shahrzad , Rakhshani Tayebeh , Mehri Zahra , Kaydani Masoumeh , Rasouli Kahaki Zeinab , Rahgoshay Niloofar , Daneshmandi Hadi
Published: November 2024

Background: Musculoskeletal disorders (MSDs) are common among nursing professionals and require effective management strategies. Implementing targeted training programs for nurses is a vital approach to reduce these problems.

Aim: This study aimed to evaluate problem‐based learning (PBL) effectiveness in reducing work‐related musculoskeletal symptoms (WMSs) among nurses.

Methods: Fifty Iranian nurses participated in this interventional study. Some data were collected by a demographic/occupational questionnaire and a Persian version of the Nordic Musculoskeletal Questionnaire (P‐NMQ). Some other was gathered by Rapid Entire Body Assessment (REBA) and PBL method.

Results: The prevalence of WMSs during the last 12 months in the subjects was related to the lower back (76%), wrists/hands (70%), neck (64%), and knee (64%), respectively. The results showed that the prevalence of WMSs decreased significantly only in the subjects’ elbow region in the postintervention (p = 0.031). Although the prevalence decreased in the postintervention stage in other regions, this decrease was not statistically significant (p > 0.05).

Conclusions: This study showed that the implementation of PBL could reduce the WMSs prevalence and the level of nurses’ exposure to risk factors for MSDs.
Impact of Depression on Cognitive Function and Phenoconversion to Neurodegenerative Diseases in Patients With Isolated REM Sleep Behavior Disorder
Authors: Moon Seock Hyeon , Hong Jung Kyung , Lee Minji , Kim Hak Hyeon , Yoon In-Young
Published: November 2024

Background: This study was aimed at analyzing cognitive function and quantitative electroencephalogram (qEEG) in patients with isolated REM sleep behavior disorder (iRBD) based on the presence of depression and at evaluating the impact of depression on phenoconversion to neurodegenerative diseases.

Methods: Individuals diagnosed with iRBD via polysomnography were included. Based on the presence of depression, patients were categorized into two groups. Neuropsychological tests and qEEG were conducted following the diagnosis of iRBD, and outcomes were compared between the two groups. Patients were regularly followed to monitor their phenoconversion status. Cox regression analysis was performed to assess the hazard ratio associated with depression.

Results: Ninety iRBD patients (70% males) were included, with a median age of 66.3 years. Depression was identified in 26 (28.9%) of these patients. The depressed group showed significantly poorer performance only in color reading subtest of Stroop (p = 0.029) compared to the nondepressed group, showing reduced processing speed. In qEEG, relative gamma power (p = 0.034) and high gamma power (p = 0.020) in the parietal region were significantly higher in the depressed group than in the nondepressed group. Depression was associated with a hazard ratio of 3.32 for the risk of phenoconversion to neurodegenerative diseases in iRBD patients (p = 0.011).

Conclusion: Depressive symptoms in iRBD patients should be closely monitored as they could aggravate cognitive dysfunction and increase the risk of phenoconversion to neurodegenerative diseases.
Jejunal Diverticular Bleeding on Long‐Term Aspirin and Short‐Term Corticosteroid Therapy
Authors: Angelopoulos Nikolaos , Beattie William , Yeoh Sern Wei
Published: November 2024

Haemorrhage is one of the most common complications of jejunal diverticula, which is a challenge to diagnose as the anatomical location of the jejunum renders it inaccessible to standard upper endoscopy, while routine imaging modalities may miss subtle or intermittent bleeding. Male gender, increasing age and colonic diverticula are known risk factors for jejunal diverticula. Nonsteroidal anti‐inflammatory drugs and corticosteroids increase gastrointestinal bleeding risk. We present a case of an 80‐year‐old male admitted to our hospital with syncope and melaena, in the setting of colonic diverticula, long‐term aspirin and short‐term corticosteroid therapy. Push enteroscopy, using a paediatric colonoscope, was pivotal to establishing the diagnosis of jejunal diverticular bleeding after gastroduodenoscopy and computed tomography (CT) angiogram were negative. Management was conservative with repeat push enteroscopy confirming the cessation of bleeding. Clinicians should consider this diagnosis when there are clinical signs of gastrointestinal bleeding in patients with known risk factors for jejunal diverticula and no evidence of location on gastroduodenoscopy, colonoscopy or imaging. We advise that push enteroscopy is performed early during the diagnostic workup to assist in identifying jejunal sources of bleeding and initiating management. However, as reflected by our case, jejunal diverticular haemorrhage may be amenable to conservative measures.
A Case of Atrial Tachycardia Masquerading as Sinus Tachycardia in a Pregnant Female—A Case Report
Authors: Javed Nismat , Ashraf Shoaib , Gore Ankita , Aziz Mohammad , Aziz Muhammad Ali , Sklyar Eduard
Published: November 2024

This case report discusses the diagnosis and management of a 25‐year‐old pregnant patient presenting with persistent tachycardia. The patient, with a past medical history of thyroiditis, polycystic ovarian syndrome, and obesity, was admitted due to palpitations and was diagnosed with atrial tachycardia. Despite medical management with metoprolol, adenosine, digoxin, and flecainide, the tachycardia persisted, necessitating discussion about cardiac ablation. The report emphasizes that atrial tachycardia poses a significant clinical challenge when refractory to medical therapy. It also highlights the condition’s association with tachycardia‐induced cardiomyopathy and the role of catheter ablation in its management. This case underscores the need for a high index of suspicion for atrial tachycardia in pregnant patients presenting with persistent tachycardia and the importance of appropriate referral for invasive management when medical therapy fails. The case also highlights that atrial tachycardia in pregnancy can be safely managed with ablation.
Efficacy of Step‐Down Therapy Using Vonoprazan for Symptomatic Mild Reflux Esophagitis
Authors: Ochiai Yorinari , Kikuchi Daisuke , Hoteya Shu
Published: November 2024

Objective: Patient‐reported outcomes (PROs) are becoming pivotal in managing gastroesophageal reflux disease (GERD). Current Japanese guidelines for GERD recommend vonoprazan (VPZ) as a treatment option for mild reflux esophagitis (RE). However, it has been hypothesized that 4 weeks of VPZ 20 mg is not always necessary for mild RE if the treatment outcome is based on patient symptoms. This study is aimed at elucidating the efficacy of a new tapering therapeutic strategy (step‐down therapy) using VPZ for symptomatic mild RE based on PRO.

Methods: This multicenter retrospective study examined VPZ’s efficacy for step‐down therapy between October 2021 and November 2022. Included were 63 consecutive patients from the outpatient clinics of Toranomon Hospital and Toranomon Hospital Kajigaya with symptoms associated with RE (frequency scale for the symptoms of GERD (FSSG) scores ≥ 8 points) and mild RE classified as the Los Angeles Classification Grade A or B. Step‐down therapy was defined as a treatment period of 28 days. VPZ 20 mg was administered as the initial treatment. Afterward, patients were allowed to step down to VPZ 10 mg if their symptoms improved, and VPZ could be discontinued if symptoms disappeared. If symptoms worsened, the dosage could be increased from 10 to 20 mg VPZ, or VPZ could be restarted at 20 mg after discontinuation.

Results: The proportion of patients whose FSSG scores decreased by ≥ 3 points with step‐down therapy was 76.2% (48/63 patients). The median FSSG scores before and after step‐down therapy were 13 (range, 8–35) and 7 (range, 0–29), respectively (p < 0.01). Overall, 71.4% (45/63) of the patients stepped down from 20 to 10 mg VPZ, and 46% (29/63) of the patients discontinued VPZ.

Conclusion: Step‐down therapy using VPZ may be a viable treatment option for symptomatic patients with mild RE.
The UBA1–STUB1 Axis Mediates Cancer Immune Escape and Resistance to Checkpoint Blockade
Authors: Bao Yi , Cruz Gabriel , Zhang Yuping , Qiao Yuanyuan , Mannan Rahul , Hu Jing , Yang Fan , Gondal Mahnoor , Shahine Miriam , Kang Sarah , Mahapatra Somnath , Chu Alec , Choi Jae Eun , Yu Jiali , Lin Heng , Miner Stephanie J. , Robinson Dan R. , Wu Yi-Mi , Zheng Yang , Cao Xuhong , Su Fengyun , Wang Rui , Hosseini Noshad , Cieslik Marcin , Kryczek Ilona , Vaishampayan Ulka , Zou Weiping , Chinnaiyan Arul M.
Published: November 2024

How cancer cells escape immune surveillance and resist immune checkpoint blockade (ICB) remains to be fully elucidated. By screening candidate genes frequently gained in cancer, we identified expression of ubiquitin-like modifier-activating enzyme 1 (UBA1) as being the most negatively correlated with signatures related to effector CD8+ T cells. High UBA1 expression was strongly predictive of treatment resistance and poor survival in ICB cohorts. Functional studies revealed that UBA1 mediated immune escape to promote tumor growth. Immune profiling further showed that Uba1 overexpression or depletion markedly decreased or increased functional intratumoral CD8+ T cells, respectively. Importantly, a selective UBA1 inhibitor, TAK-243, significantly synergized with ICB in multiple syngeneic models. Mechanistically, depletion or inactivation of the UBA1–STUB1 axis stabilized a key IFN pathway component (JAK1), enhanced IFN signaling, and elevated key immune modulators, including CXCL9, CXCL10, and MHC class I. Our study warrants clinical evaluation of the combination of UBA1 inhibitors and ICB.

Significance:

Our study reveals UBA1 as a predictive biomarker for clinical outcomes in ICB cohorts, mediating cancer immune evasion and ICB resistance. We further highlight JAK1 stabilization as a key mechanism of UBA1 inhibition and nominate the UBA1–STUB1 axis as an immuno-oncology therapeutic target to improve the efficacy of ICB.
Supplementary Figure S.8 from Mathematical Modeling Unveils Optimization Strategies for Targeted Radionuclide Therapy of Blood Cancers
Authors: Kuznetsov Maxim , Adhikarla Vikram , Caserta Enrico , Wang Xiuli , Shively John E. , Pichiorri Flavia , Rockne Russell C.
Published: November 2024

Supplementary Figure S.8
Supplementary Figure S.27 from Mathematical Modeling Unveils Optimization Strategies for Targeted Radionuclide Therapy of Blood Cancers
Authors: Kuznetsov Maxim , Adhikarla Vikram , Caserta Enrico , Wang Xiuli , Shively John E. , Pichiorri Flavia , Rockne Russell C.
Published: November 2024

Supplementary Figure S.27
Supplementary Figure S.25 from Mathematical Modeling Unveils Optimization Strategies for Targeted Radionuclide Therapy of Blood Cancers
Authors: Kuznetsov Maxim , Adhikarla Vikram , Caserta Enrico , Wang Xiuli , Shively John E. , Pichiorri Flavia , Rockne Russell C.
Published: November 2024

Supplementary Figure S.25
Supplementary Figure S.24 from Mathematical Modeling Unveils Optimization Strategies for Targeted Radionuclide Therapy of Blood Cancers
Authors: Kuznetsov Maxim , Adhikarla Vikram , Caserta Enrico , Wang Xiuli , Shively John E. , Pichiorri Flavia , Rockne Russell C.
Published: November 2024

Supplementary Figure S.24
Supplementary Figure S.17 from Mathematical Modeling Unveils Optimization Strategies for Targeted Radionuclide Therapy of Blood Cancers
Authors: Kuznetsov Maxim , Adhikarla Vikram , Caserta Enrico , Wang Xiuli , Shively John E. , Pichiorri Flavia , Rockne Russell C.
Published: November 2024

Supplementary Figure S.17
Supplementary Figure S.14 from Mathematical Modeling Unveils Optimization Strategies for Targeted Radionuclide Therapy of Blood Cancers
Authors: Kuznetsov Maxim , Adhikarla Vikram , Caserta Enrico , Wang Xiuli , Shively John E. , Pichiorri Flavia , Rockne Russell C.
Published: November 2024

Supplementary Figure S.14
Figure 3 from Mathematical Modeling Unveils Optimization Strategies for Targeted Radionuclide Therapy of Blood Cancers
Authors: Kuznetsov Maxim , Adhikarla Vikram , Caserta Enrico , Wang Xiuli , Shively John E. , Pichiorri Flavia , Rockne Russell C.
Published: November 2024

Dependence of minimal single curative dose, Acur, on the coefficient of drug impurity, η, i.e., the ratio of unlabeled antibodies to radioconjugates. A, Moderate variation in η. Under significant self-damage, saturation of specific receptors leads to redirection of radioconjugates and deposited doses toward still viable cells, which continue generating specific receptors. This effect yields the decrease in Acur with an increase in η. B, Extended variation of η. The curative treatment becomes lethally toxic shortly after the amount of injected antibodies, (η + 1)Acur, exceeds the total amount of specific receptors expressed on cancer cells during treatment.
Identification of ncRNA Biomarkers in Non–Small Cell Lung Cancer to Address Racial Disparities
Authors: Gao Lu , Dhilipkannah Pushpa , Jiang Feng
Published: November 2024

Lung cancer significantly impacts mortality, with African Americans (AA) showing higher rates than White Americans (WA). ncRNAs play a crucial role in lung tumorigenesis. To identify ncRNA biomarkers associated with racial disparities in lung cancer, we used droplet digital PCR to examine 93 lung cancer–associated ncRNAs in plasma and sputum samples from participants of AA and WA backgrounds, including 118 patients and 92 cancer-free smokers. In the AA population, plasma showed differential expression of 10 ncRNAs, whereas sputum revealed four ncRNAs when comparing patients with lung cancer to the control group. In the WA population, the plasma displayed 11 ncRNAs, and the sputum had five ncRNAs showing differential expression between patients with lung cancer and the control group. For AAs, we identified a three-ncRNA panel (plasma miRs–147b, 324-3p, and 422a) for diagnosing lung cancer in AAs with 86% sensitivity and 89% specificity. For WAs, a four-ncRNA panel comprising sputum miR-34a-5p and plasma miRs–103-3p, 126-3p, and 205-5p was developed, achieving 88% sensitivity and 87% specificity. These panels remained effective across various stages and types of lung tumors and were validated in an independent cohort of 56 patients and 72 controls. Ethnicity-related ncRNA signatures hold promise as biomarkers for tackling racial disparities in patients with lung cancer.

Significance:

This study identifies ethnicity-related ncRNA biomarkers that differentiate lung cancer in AAs and WAs, offering diagnostic panels with high sensitivity and specificity. These findings provide a promising approach to addressing racial disparities in lung cancer detection and improving early diagnosis across diverse populations.
Comprehensive Analysis of Radiologic Cancer-Free Status through Various Treatment Approaches in Advanced-Stage Hepatocellular Carcinoma
Authors: Koroki Keisuke , Ogasawara Sadahisa , Izai Ryo , Yonemoto Takuya , Akatsuka Teppei , Miwa Chihiro , Yumita Sae , Inoue Masanori , Kobayashi Kazufumi , Kiyono Soichiro , Nakamura Masato , Kanogawa Naoya , Kondo Takayuki , Nakamoto Shingo , Nakada Shinichiro , Sakai Nozomu , Yokoyama Masayuki , Ohtsuka Masayuki , Kato Naoya
Published: November 2024

Introduction: In the realm of oncology, the pinnacle of therapeutic success is achieving a state where the patient is entirely free of cancer, i.e., “cancer free.” This benchmark should not only apply to early-stage malignancies but should also be the standard aim for advanced-stage diseases, including hepatocellular carcinoma (HCC). However, there is a glaring gap in the research landscape concerning the understanding of what cancer-free status truly means for advanced-stage HCC. Our study sheds light on the profound implications of reaching a cancer-free by radiologic assessments in patients with advanced-stage HCC. Methods: We established a database tracking the full clinical course of all patients with HCC (from 2003 to 2022). We identified the initial instances of macrovascular invasion or extrahepatic spread. We defined radiologic cancer-free (rCF) as cases in which no recurrence was observed for at least 2 months following curative treatment or complete response to systemic therapies. The frequency of achieving rCF status was investigated, categorized by patients’ background. Results: We identified 795 patients with advanced-stage HCC. The rCF rate was 8.7%. Patients who achieved rCF status had significantly better prognoses compared to those who did not (p < 0.001). In the decision tree analysis, the number of tumors ≥8 was the strongest factor, making it difficult to achieve rCF status. Analysis of stage progression patterns revealed varying background characteristics at the time of advanced-stage diagnosis, with discrepancies in rCF rates. Conclusions: Despite the low rate of achieving rCF status, the prognostic impact was significant. Patients with certain tumor characteristics had a higher likelihood of achieving rCF status. The distribution of tumor conditions varies based on the pattern of progression, which affects the likelihood of achieving an rCF status.
VEGFC Overexpression in Kidney Progenitor Cells Is a Model of Renal Lymphangiectasia—Brief Report
Authors: Donnan Michael D. , Deb Dilip K. , Dalal Vidhi , David Valentin , Procissi Daniele , Quaggin Susan E.
Published: November 2024

BACKGROUND:

Lymphangiogenesis is believed to be a protective response in the setting of multiple forms of kidney injury and mitigates the progression of interstitial fibrosis. To augment this protective response, promoting kidney lymphangiogenesis is being investigated as a potential treatment to slow the progression of kidney disease. As injury-related lymphangiogenesis is driven by signaling from the receptor VEGFR3 (vascular endothelial growth factor receptor 3) in response to the cognate growth factor VEGF (vascular endothelial growth factor)-C released by tubular epithelial cells, this signaling pathway is a candidate for future kidney therapeutics. However, the consequences to kidney development and function to targeting this signaling pathway remain poorly defined.

METHODS:

We generated a new mouse model expressing
Vegfc
under regulation of the nephron progenitor Six2Cre driver strain (
Six2Vegfc
). Mice underwent a detailed phenotypic evaluation. Whole kidneys were processed for histology and 3-dimensional imaging.

RESULTS:

Six2Vegfc
mice had reduced body weight and kidney function compared with littermate controls.
Six2Vegfc
kidneys demonstrated large peripelvic fluid-filled lesions with distortion of the pelvicalcyceal system which progressed in severity with age. Three-dimensional imaging showed a 3-fold increase in total cortical vascular density. Histology confirmed a substantial increase in LYVE1+ (lymphatic vessel endothelial hyaluronan receptor-1)/PDPN+ (podoplanin)/VEGFR3+ lymphatic capillaries extending alongside EMCN+ (endomucin) peritubular capillaries. There was no change in EMCN+ peritubular capillary density.

CONCLUSIONS:

Kidney lymphatic density was robustly increased in the
Six2Vegfc
mice. There were no changes in peritubular blood capillary density despite these endothelial cells also expressing VEGFR3. The model resulted in malformation of the lymphatic hilar plexus, resulting in severe hydronephrosis that resembled a human condition termed renal lymphangiectasia. This study defines the vascular consequences of augmenting VEGFC signaling during kidney development and provides new insight into human renal lymphatic malformations.
Emerging Imaging Techniques for Atherosclerosis in Systemic Immune-Mediated Inflammatory Conditions
Authors: Markousis-Mavrogenis George , Habib Muzzamal , Huck Daniel M. , André Florian , Steen Henning , Mukherjee Monica , Mavrogeni Sophie I. , Weber Brittany
Published: November 2024

Atherosclerosis affects patients with systemic immune-mediated inflammatory diseases at an increased rate compared with the general population. In recent years, our understanding of the pathophysiology of atherosclerosis has advanced considerably. Nevertheless, cardiovascular imaging modalities that can adequately assess the biological background of atherosclerosis have not reached widespread clinical adoption. Novel developments in cardiac imaging have the potential to enhance the diagnostic yield of these modalities further while providing essential insights into the anatomy, composition, and biology of atherosclerotic lesions. In this review, we highlight some of the latest developments in the field for the evaluation of atherosclerosis using advances in echocardiography, computed tomography, positron emission tomography, and cardiovascular magnetic resonance. Additionally, we discuss evidence specifically in patients with immune-mediated inflammatory diseases and outline unmet research needs for future development.