bluuebunny/crossref_metadata_2025 huggingface dataset:
Four-Velocity and Time in Special Relativity
Authors: Riggs Peter J.
Published: December 2022

Four-vectors are defined analogously to three-vectors and provide a compact means of presenting mathematical results in relativity theory. However, the four-velocity vector does not have the same physical significance as the three-velocity vector, but assuming so has led to the declaration that there is motion through spacetime which explains special relativistic time dilation. It is shown that four-velocity cannot legitimately be employed in this manner and that the time dilation effect does not require any motion through spacetime nor any speed through time.
From volcanoes to sedimentary systems
Authors: Di Capua Andrea , De Rosa Rosanna , Kereszturi Gabor , Le Pera Emilia , Rosi Mauro , Watt Sebastian F. L.
Published: December 2022

Volcanoes produce probably the most spectacular geological phenomena on Earth. Any of their eruptions can have a strong consequence on the surrounding environment, often captured in great detail in the sedimentary records of volcanically active regions. In addition, flank landslides and background erosive processes affecting volcanic sequences release volcanic particles that circulate within sedimentary environments up to billions of years after their generation. Therefore, exploring volcanically influenced sedimentary environments is an exciting and challenging scientific exercise requiring insights across multiple geological disciplines, drawing upon an increasing varied range of expertise and analytical approaches from across the geoscientific community. This book aims to provide an updated collection of works that illustrate the state-of-the-art in this topic, and to define the future directions of the geological sciences in utilizing and interpreting sedimentary records of volcanism.
Along-strike magma-poor/magma-rich spreading transitions
Authors: Nemčok Michal , Frost Brian
Published: December 2022

1D/2D data-based studies of active spreading centres brought the knowledge of extension rate-dependent stretching-dominated v. buoyancy-dominated spreading. 3D reflection seismic data from the extinct centre of an initial oceanic corridor in the Caribbean allow us to see an along-strike transition between stretching- and buoyancy-dominated spreading where the spreading through detachment faulting is a precursor to the magma-assisted spreading. Studying progressively more evolved portions of the spreading centre, going from its end towards its centre, we see a progressively higher ascent of the asthenosphere, which heats the developing core complex in the exhuming footwall of the initial stretching-dominated system. The asthenospheric ascent is associated with thermal weakening of the core complex, which eventually results in ductile deformation reaching the upper portion of the complex. Subsequently, the core complex is penetrated by the dyke located at the top of the asthenospheric body. The dyke, which subsequently evolves to a diapir-shaped body, reaches the sea floor and establishes a magma-assisted steady-state seafloor spreading. These observations lead to a model explaining the initiation of the magma-assisted spreading in the initial oceanic corridor. Furthermore, they also improve our knowledge of multiple interacting mechanisms involved in the breakup of the last continental lithospheric layer, subsequent disorganized spreading and younger organized spreading.
The text-privileging infrastructures of academic journals
Authors: Gilbert Carrie Clegg
Published: December 2022

There is a gap in the academic literature examining how visual elements enhance verbal communication. We intuitively know that a well-placed graph or diagram can help get a complex point across, but the "how"s and "why"s remain more art than science. When you look at the average academic journal, this shortage of visual research is not so surprising. Despite all the urgent dialog in recent years about multimodalities and visual literacy, the publishing process makes it very difficult to challenge this "text first" status quo.
HateCircle and Unsupervised Hate Speech Detection Incorporating Emotion and Contextual Semantics
Authors: Ghosal Sayani , Jain Amita
Published: December 2022

The explosive growth of social media has fueled an extensive increase in online freedom of speech. The worldwide platform of human voice creates possibilities to assail other users without facing any consequences, and flout social etiquettes, resulting in an inevitable increase of hate speech. Nowadays, English hate speech detection is a popular research area, but the prevalence of implicit hate content in regional languages desire effective language-independent models. The proposed research is the first unsupervised Hindi and Bengali hate content detection framework consisting of three significant concepts: HateCircle, hate tweet classification, and code-switch data preparation algorithms. The novel HateCircle method is proposed to detect hate orientation for each term by co-occurrence patterns of words, contextual semantics, and emotion analysis. The efficient multiclass hate tweet classification algorithm is proposed with parts of speech tagging, Euclidean distance, and the Geometric median methods. The detection of hate content is more efficient in the native script compared to the Roman script, so the transliteration algorithm is also proposed for code-switch data preparation. The experimentation evaluates the combination of various lexicons with our enriched hate lexicon that achieves a maximum of 0.74 F1-score for the Hindi and 0.88 F1-score for the Bengali datasets. The novel HateCircle and hate tweet detection framework evaluates with our proposed parts of speech tagging and Geometric median detection methods. Results reveal that HateCircle and hate tweet detection framework also achieves a maximum of 0.73 accuracy for the Hindi and 0.78 accuracy for the Bengali dataset. The experiment results signify that contextual semantic hate speech detection research with a language-independency feature offsets the growth of implicit abusive text in social media.
ITU-T Standardization Activities Targeting Gaming Quality of Experience
Authors: Schmidt Steven , Zadtootaghaj Saman , Möller Sebastian
Published: December 2022

For more information about the gaming activities described in this report, please contact Sebastian Möller (sebastian.moeller@tu-berlin.de).
Sulforaphane attenuates cancer cell-induced atrophy of C2C12 myotubes
Authors: Li Wenlan , Trieu Jennifer , Blazev Ronnie , Parker Benjamin L. , Murphy Kate T. , Swiderski Kristy , Lynch Gordon S.
Published: December 2022

Cancer cachexia is common in many cancers and the loss of skeletal muscle mass compromises the response to therapies and quality of life. A contributing mechanism is oxidative stress and compounds able to attenuate it may be protective. Sulforaphane (SFN), a natural antioxidant in cruciferous vegetables, activates nuclear factor erythroid 2-related factor 2 (Nrf2) signaling to decrease oxidative stress. Although SFN has potential as a cancer therapeutic, whether it can attenuate muscle wasting in the absence or presence of chemotherapy is unknown. In healthy C2C12 myotubes, SFN administration for 48 h induced hypertrophy through increased myoblast fusion via Nrf2 and ERK signaling. To determine whether SFN could attenuate wasting induced by cancer cells, myotubes were cocultured with or without Colon-26 (C-26) cancer cells for 48 h and treated with 5-fluorouracil (5-FU, 5 µM) or vehicle (DMSO). SFN (10 µM) or DMSO was added for the final 24 h. Coculture with cancer cells in the absence and presence of 5-FU reduced myotube width by ∼30% ( P < 0.001) and ∼20% ( P < 0.01), respectively, which was attenuated by SFN ( P < 0.05). Exposure to C-26 conditioned media reduced myotube width by 15% ( P < 0.001), which was attenuated by SFN. Western immunoblotting and qRT-PCR confirmed activation of Nrf2 signaling and antioxidant genes. Coadministration of Nrf2 inhibitors (ML-385) or MEK inhibitors (PD184352) revealed that SFN’s attenuation of atrophy was blocked by ERK inhibition. These data support the chemoprotective and antioxidative function of SFN in myotubes, highlighting its therapeutic potential for cancer-related muscle wasting.
Differential MMP-14 targeting by biglycan, decorin, fibromodulin, and lumican unraveled by in silico approach
Authors: Rivet Romain , Rao Rajas Mallenahalli , Nizet Pierre , Belloy Nicolas , Huber Louise , Dauchez Manuel , Ramont Laurent , Baud Stéphanie , Brézillon Stéphane
Published: December 2022

Small leucine-rich proteoglycans (SLRPs) are major regulators of extracellular matrix assembly and cell signaling. Lumican, a member of the SLRPs family, and its derived peptides were shown to possess antitumor activity by interacting directly with the catalytic domain of MMP-14 leading to the inhibition of its activity. The aim of the present report was to characterize by in silico three-dimensional (3D) modeling the structure and the dynamics of four SLRPs including their core protein and their specific polysaccharide chains to assess their capacity to bind to MMP-14 and to regulate its activity. Molecular docking experiments were performed to identify the specific amino acids of MMP-14 interacting with each of the four SLRPs. The inhibition of each SLRP (100 nM) on MMP-14 activity was measured and the constants of inhibition ( Ki) were evaluated. The impact of the number of glycan chains, structures, and dynamics of lumican on the interaction with MMP-14 was assessed by molecular dynamics simulations. Molecular docking analysis showed that all SLRPs bind to MMP-14 through their concave face, but in different regions of the catalytic domain of MMP-14. Each SLRPs inhibited significantly the MMP-14 activity. Finally, molecular dynamics showed the role of glycan chains in interaction with MMP-14 and shielding effect of SLRPs. Altogether, the results demonstrated that each SLRP exhibited inhibition of MMP-14 activity. However, the differential targeting of MMP-14 by the SLRPs was shown to be related not only to the core protein conformation but also to the glycan chain structures and dynamics.
Calligraphy and Painting Identification 3D-CNN Model Based on Hyperspectral Image MNF Dimensionality Reduction
Authors: XingJia Tang , PengChang Zhang , ZongBen Xu , BingLiang Hu
Published: December 2022

As a kind of cultural art, calligraphy and painting are not only an important part of traditional culture but also has important value of art collection and trade. The existence of forgeries has seriously affected the fair trade, protection, and inheritance of calligraphy and painting. There is an urgent need for the efficient, accurate, and intelligent technical identification method. By combining the advantages of material attribute recognition and imaging detection of hyperspectral imaging technology with the powerful feature expression ability and classification ability of the convolutional neural network, it can greatly improve the comprehension efficiency of calligraphy and painting identification; meanwhile, in order to reduce the redundancy and the amount of parameters in the method of directly using the hyperspectral image, an objective convex dimensionality reduction method should be used for compressing the original hyperspectral image before deep learning. Based on this, we propose a kind of deep learning method to classify author and authenticity based on the multichannel images obtained by minimum noise fraction (MNF) dimensionality reduction to calligraphy and painting hyperspectral data, and its core is the 2D-CNN or 3D-CNN model with the basic network of “4 convolution layers + 4 pooling layers + 2 full-link layers.” The experimental results show that the identification accuracy of the 2D-CNN calligraphy and painting identification with MNF pseudocolor image mosaic as input and the 2D-CNN calligraphy and painting identification with multichannel MNF dimensionality reduced images direct as input have high accuracy, while the 3D-CNN calligraphy and painting identification with multichannel MNF dimensionality reduced images direct as input not only maintains excellent identification accuracy but also has better learning convergence (step number) and stability compared with the 2D-CNN model. Especially, the 3D-CNN identification accuracy of calligraphy and painting’s author and authenticity on the test set can reach 93.2% and 95.2%, respectively.
Recent Updates on the Role of the MicroRNA-10 Family in Gynecological Malignancies
Authors: Li Chunhua , Zhu Xiangling , Lv Xinyue , Han Xintong , Xu Yuting , Huang Jinhua , Chen Xiaochun , Yu Zhiying
Published: December 2022

The ever-increasing morbidity associated with gynecological malignancies constantly endangers the physical and psychological health of women. Since a long time, there has been an urgent need for a deeper understanding of the tumorigenesis and the development of gynecological cancer to identify new molecular markers for early diagnosis and metastatic disease prognosis and for the development of therapeutic targets. MicroRNAs are crucial cellular regulators. The microRNA-10 (miR-10) family has been found to play an integral role in the evolution of numerous cancer types. A comprehensive understanding of current studies on miR-10 could provide better insights into future research and clinical applications in related fields. This article reviews the latest research on the role of the miR-10 family in gynecological malignancies and the relevant molecular mechanism, mainly focusing on endometrial, cervical, and ovarian cancers.
Modelling the Role of Treatment, Public Health Education, and Chemical Control Strategies on Transmission Dynamics of Schistosomiasis
Authors: Kamara Timothy , Byamukama Michael , Karuhanga Martin
Published: December 2022

In this study, a mathematical model for the transmission dynamics and control of schistosomiasis is studied using a system of nonlinear ordinary differential equations. The basic reproduction number ℛ0 for the model is obtained, and its dependence on model parameters is discussed. Analytical results reveal that the disease‐free equilibrium point is globally stable if and only if the basic reproduction number ℛ0 < 1, indicating that the disease would be wiped out of the community, and the endemic equilibrium point is globally stable if ℛ0 > 1 and the disease would persist at the endemic steady state. Numerical simulations reveal that a combination of treatment, public health education, and chemical control intervention strategies significantly increased the number of susceptible human population and susceptible snail population while significantly decreasing the number of infected humans, miracidia, infected snails, and cercariae. The results further indicate that a combination of treatment, public health education, and chemical control intervention strategies can effectively manage the transmission of schistosomiasis in endemic areas.
Manipulating the Laser-Driven Proton Bunch with Plasma Wakefield
Authors: Jin Chao , Zhao Xiao-ying , Cai Han-jie , Qi Xin , Wang Zhi-jun , He Yuan , Zhao Yongtao
Published: December 2022

With the advantages of short duration and extreme brightness, laser
proton accelerators (LPAs) show great potential in many fields for
industrial, medical, and research applications. However, the quality of
current laser-driven proton beams, such as the broad energy spread and large
divergence angle, is still a challenge. We use numerical simulations to
study the propagation of such proton bunches in the plasma. Results show the
bunch will excite the wakefield and modulate itself. Although a small number
of particles at the head of the bunch cannot be manipulated by the
wakefield, the total energy spread is reduced. Moreover, while reducing the
longitudinal energy spread, the wakefield will also pinch the beam in the
transverse direction. The space charge effect of the bunch is completely
offset by the wakefield, and the transverse momentum of the bunch decreases
as the bunch transports in the plasma. For laser-driven ion beams, our study
provides a novel idea about the optimization of these beams.
Comparing Long-Term Outcomes of Entecavir and Tenofovir Disoproxil Fumarate in Liver Transplant Patients
Authors: Zhao Tingxiao , Yang Zhe , Yu Jiong , Lu Juan , Li Lanjuan , Xu Xiao , Cao Hongcui , Zheng Shusen
Published: December 2022

Objectives. There are no detailed reports on the long-term outcome of patients treated with tenofovir disoproxil fumarate (TDF) compared with entecavir (ENT) following liver transplantation. We aimed to assess the association between TDF use and long-term outcome compared to recipients using ENT. Methods. This retrospective observational study included patients who underwent liver transplantation between January 2015 and May 2019 at the First Affiliated Hospital of Zhejiang University School of Medicine and Hangzhou Shulan Hospital. Cox regression, propensity score matching (PSM), and inverse probability of treatment weighting (IPTW) were performed to assess HBV recurrence, renal dysfunction, and patient survival in liver transplant patients treated with TDF compared with ENT. Results. A total of 907 patients met the inclusion criteria and were included in the final analysis, among which, there were 109 (12.0%) patients treated with TDF and 798 (88.0%) patients treated with ENT. During the follow-up period, 166 patients died, 15 (13.8%) in the TDF group, and 151 (18.9%) in the ENT group. No significant association was found between TDF or ENT use and patient survival (HR, 0.72, 95% CI 0.41-1.23;

P
=
0.226

) by PSM analysis. Similarly, differences in the antiviral agents were not significantly associated with hepatitis B recurrence (HR, 1.19, 95% CI 0.62-2.28;

P
=
0.603

), but TDF use was significantly related to renal dysfunction after liver transplantation (HR 1.70, 95% CI, 1.21-2.37;

P
=
0.002

). Similar results were obtained in subsequent sensitivity analyses. Conclusions. In this study, the results showed that the use of TDF after liver transplantation is as safe and effective as the use of ENT in preventing hepatitis B recurrence. However, renal function in recipients treated with TDF requires careful monitoring.
Metabolism-Related Gene TXNRD1 Regulates Inflammation and Oxidative Stress Induced by Cigarette Smoke through the Nrf2/HO-1 Pathway in the Small Airway Epithelium
Authors: Huang Qian , Peng Maocuo , Gu Yiya , Wu Jixing , Zhan Yuan , Deng Zhesong , Chen Shanshan , Yang Ruonan , Chen Jinkun , Xie Jungang
Published: December 2022

Chronic obstructive pulmonary disease (COPD), a small airway disease, is regarded as a metabolic disorder. To further uncover the metabolic profile of COPD patients, it is necessary to identify metabolism-related differential genes in small airway epithelium (SAE) of COPD. Metabolism-related differential genes in SAE between COPD patients and nonsmokers were screened from GSE128708 and GSE20257 datasets. KEGG, GO, and PPI analyses were performed to evaluate the pathway enrichment, term enrichment, and protein interaction of candidate metabolism-related differential genes, respectively. RT-PCR was used to verify the mRNA expression of the top ten differential genes. Western blotting was used to evaluate the protein expression of TXNRD1. TXNRD1 inhibitor auranofin (AUR) was used to assess the impact of TXNRD1 on oxidative stress and inflammation induced by cigarette smoke extraction (CSE). Twenty-four metabolism-related differential genes were selected. ALDH3A1, AKR1C3, CYP1A1, AKC1C1, CPY1B1, and TXNRD1 in the top ten genes were significantly upregulated after CSE simulation for 24 h in human bronchial epithelial (16HBE) cells. Among them, CYP1A1 and TXNRD1 also have a significant upregulation in primary SAE after simulation of CSE for 24 h. The overexpression of protein TXNRD1 has also been detected in 16HBE cells, primary SAE stimulated with CSE, and mouse lung exposed to cigarette smoke (CS). Additionally, inhibition of TXNRD1 with 0.1 μM AUR alleviated the expression of IL-6 and reactive oxygen species (ROS) induced by CSE by activating the Nrf2/HO-1 pathway in 16HBE cells. This study identified twenty-four metabolism-related differential genes associated with COPD. TXNRD1 might participate in the oxidative stress and inflammation induced by CS by regulating the activation of the Nrf2/HO-1 pathway.
METTL14 Regulates Intestine Cellular Senescence through m6A Modification of Lamin B Receptor
Authors: Zhang Zizhen , Xue Meng , Chen Jingyu , Wang Zhuo , Ju Fangyu , Ni Jiaojiao , Sun Jiawei , Wu Haoyue , Zheng Huimei , Lou Ziwei , Zhang Yawen , Yang Xiaohang , Chen Shujie , Xi Yongmei , Wang Liangjing
Published: December 2022

N-6-Methyladenosine (m6A) modification is involved in multiple biological processes including aging. However, the regulation of m6A methyltransferase-like 14 (METTL14) in aging remains unclear. Here, we revealed that the level of m6A modification and the expression of METTL14 were particularly decreased in the intestine of aged mice as compared to young mice. Similar results were confirmed in Drosophila melanogaster. Knockdown of Mettl14 in Drosophila resulted in a short lifespan, associated disrupted intestinal integrity, and reduced climbing ability. In human CCD-18Co cells, knockdown of METTL14 accelerated cellular senescence, and the overexpression of METTL14 rescued senescent phenotypes. We also identified the lamin B receptor (LBR) as a target gene for METTL14-mediated m6A modification. Knockdown of METTL14 decreased m6A level of LBR, resulted in LBR mRNA instability, and thus induced cellular senescence. Our findings suggest that METTL14 plays an essential role in the m6A modification-dependent aging process via the regulation of LBR and provides a potential target for cellular senescence.
Eccentric Harmonic Index for the Cartesian Product of Graphs
Authors: Jebreen Kamel , Aftab Muhammad Haroon , Sowaity M. I. , Sharada B. , Naji A. M. , Pavithra M.
Published: December 2022

Suppose ρ is a simple graph, then its eccentric harmonic index is defined as the sum of the terms 2/ea + eb for the edges vavb, where ea is the eccentricity of the ath vertex of the graph ρ. We symbolize the eccentric harmonic index (EHI) as He = He(ρ). In this article, we determine He for the Cartesian product (CP) of particularly chosen graphs. Lower bounds for He of the CP of the two graphs are established. The formulas of EHI for the Hamming and Hypercube graphs are obtained. These obtained formulas can be used in QSAR and QSPR studies to get a better understanding of their applications in mathematical chemistry.
Electrophysiological Changes of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes during Acute Hypoxia and Reoxygenation
Authors: Häkli Martta , Kreutzer Joose , Mäki Antti-Juhana , Välimäki Hannu , Cherian Reeja Maria , Kallio Pasi , Aalto-Setälä Katriina , Pekkanen-Mattila Mari
Published: December 2022

Ischemic heart disease is the most common cardiovascular disease and a major burden for healthcare worldwide. However, its pathophysiology is still not fully understood, and human-based models for disease mechanisms and treatments are needed. Here, we used human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to model acute ischemia-reperfusion in our novel cell culture assembly. The assembly enables exchange of oxygen partial pressure for the cells within minutes, mimicking acute ischemic event. In this study, hypoxia was induced using 0% O2 gas for three hours and reoxygenation with 19% O2 gas for 24 hours in serum- and glucose-free medium. According to electrophysiological recordings, hypoxia decreased the hiPSC-CM-beating frequency and field potential (FP) amplitude. Furthermore, FP depolarization time and propagation slowed down. Most of the electrophysiological changes reverted during reoxygenation. However, immunocytochemical staining of the hypoxic and reoxygenation samples showed that morphological changes and changes in the sarcomere structure did not revert during reoxygenation but further deteriorated. qPCR results showed no significant differences in apoptosis or stress-related genes or in the expression of glycolytic genes. In conclusion, the hiPSC-CMs reproduced many characteristic changes of adult CMs during ischemia and reperfusion, indicating their usefulness as a human-based model of acute cardiac ischemia-reperfusion.
Evaluation of a Liquid Biopsy-Breast Cancer Methylation (LBx-BCM) Cartridge Assay for Predicting Early Disease Progression and Survival: TBCRC 005 Prospective Trial
Authors: Visvanathan Kala , Cope Leslie , Fackler Mary Jo , Considine Michael , Sokoll Lori , Carey Lisa A. , Forero-Torres Andres , Ingle James N. , Lin Nancy U. , Nanda Rita , Storniolo Anna Maria , Tulac Suzana , Venkatesan Neesha , Wu Natalie C. , Marla Sudhakar , Campbell Scott , Bates Michael , Umbricht Christopher B. , Wolff Antonio C. , Sukumar Saraswati
Published: December 2022

Purpose:

We previously demonstrated that high levels of circulating methylated DNA are associated with subsequent disease progression in women with metastatic breast cancer (MBC). In this study, we evaluated the clinical utility of a novel liquid biopsy-breast cancer methylation (LBx-BCM) prototype assay using the GeneXpert cartridge system for early assessment of disease progression in MBC.

Experimental Design:

The 9-marker LBx-BCM prototype assay was evaluated in TBCRC 005, a prospective biomarker study, using plasma collected at baseline, week 4, and week 8 from 144 patients with MBC.

Results:

At week 4, patients with MBC with high cumulative methylation (CM) had a significantly shorter median PFS (2.88 months vs. 6.60 months, P = 0.001) and OS (14.52 months vs. 22.44 months, P = 0.005) compared with those with low CM. In a multivariable model, high versus low CM was also associated with shorter PFS (HR, 1.90; 95% CI, 1.20–3.01; P = 0.006). Change in CM from baseline to week 4 (OR, 4.60; 95% CI, 1.77–11.93; P = 0.002) and high levels of CM at week 4 (OR, 2.78; 95% CI, 1.29–5.99; P = 0.009) were associated with progressive disease at the time of first restaging. A robust risk model based on week 4 circulating CM levels was developed to predict disease progression as early as 3 months after initiating a new treatment.

Conclusions:

The automated LBx-BCM prototype assay is a promising clinical tool for detecting disease progression a month after initiating treatment in women with MBC undergoing routine care. The next step is to validate its clinical utility for specific treatments.
Molecular Clusters and Tumor-Immune Drivers of IgM Monoclonal Gammopathies
Authors: Mondello Patrizia , Paludo Jonas , Novak Joseph P. , Wenzl Kerstin , Yang Zhi-Zhang , Jalali Shahrzad , Krull Jordan E. , Braggio Esteban , Dasari Surendra , Manske Michelle K. , Abeykoon Jithma A. , Sarangi Vivekananda , Kapoor Prashant , Paulus Aneel , Reeder Craig B. , Ailawadhi Sikander , Chanan-Khan Asher A. , Kyle Robert A. , Gertz Morie A. , Novak Anne J. , Ansell Stephen M.
Published: December 2022

Purpose:

IgM monoclonal gammopathy of undetermined significance (MGUS) and Waldenström macroglobulinemia (WM) represent a disease spectrum with highly varied therapeutic management, ranging from observation to chemoimmunotherapy. The current classification relies solely on clinical features and does not explain the heterogeneity that exists within each of these conditions. Further investigation is warranted to shed light on the biology that may account for the clinical differences.

Experimental Design:

We used bone marrow (BM) clonal CD19+ and/or CD138+ sorted cells, matched BM supernatant, and peripheral blood serum from 32 patients (7 MGUS, 25 WM) to perform the first multi-omics approach including whole-exome sequencing, RNA sequencing, proteomics, metabolomics, and mass cytometry.

Results:

We identified three clusters with distinct pathway activation, immune content, metabolomic, and clinical features. Cluster 1 included only patients with WM and was characterized by transcriptional silencing of genes involved in cell cycle and immune response, enrichment of mitochondrial metabolism, infiltration of senescent T effector memory cells, and aggressive clinical behavior. Genetic/structural alterations of TNFAIP3 were distinct events of this cluster. Cluster 2 comprised both MGUS and WM patients with upregulation of inflammatory response, senescence and glycolysis signatures, increased activated T follicular helper and T regulatory cells, and indolent clinical behavior. Cluster 3 also included both MGUS and WM patients and exhibited intermediate features, including proliferative and inflammatory signaling, as well as glycolysis and mitochondrial metabolism.

Conclusions:

We have identified three distinct molecular clusters, suggesting a potential biologic classification that may have therapeutic implications.
Genetic Modeling of B-cell State Transitions for Rational Design of Lymphoma Therapies
Authors: Leveille Etienne , Kothari Shalin , Müschen Markus
Published: December 2022

The use of genomic data to analyze primary endpoints for clinical trials in diffuse large B-cell lymphomas (DLBCL) significantly improved the development of rational drug combinations for genetically defined patient subsets. Recent genetic mouse models and their ability to recapitulate transitions between germinal center exit and memory B-cell characteristics in DLBCL will accelerate the development of rationale-based clinical trials.

See related article by Flümann et al., p. 78 (3).

See related article by Venturutti et al., (5).
Patellar Tendon Avulsion in a Pediatric Male: A Surgical Case Report with a Return to Sport
Authors: Hladish Stacey , Donnay Rebecca , Henry Jon , Voss Mitchell
Published: December 2022

Isolated patellar tendon injuries in the pediatric population are considered rare and lack a well-accepted classification system. This injury pattern in pediatrics occurs more commonly in males around 14 years of age, typically presents with apophyseal involvement, and is frequently associated with athletic activity. The patient, in this case, was a 12-year-old male who sustained an isolated distal patellar tendon injury while running. This case is unique due to lack of apophyseal involvement commonly seen in the pediatric population. On exam, a classic high-riding patella was not seen on initial X-ray, and he was able to actively extend his knee, two clinical clues associated with the diagnostic triad of patellar tendon injury. Magnetic resonance imaging was utilized to confirm the injury pattern which prompted urgent surgical intervention to allow for initiation of rehabilitation with a goal of returning to athletic activities. The patient was able to progress to full weight-bearing at 1.5 months, achieved full range of motion at 3 months, demonstrated symmetric strength with uninvolved lower extremity at 4.5 months, and had progressed back into sporting activities by 5.75 months postoperatively. The low frequency of this injury in the pediatric population requires urgent recognition and diagnosis to allow for prompt surgical intervention followed by rehabilitation for efficient return to play.
Impending Compartment Syndrome Secondary to Pseudoaneurysm following Stabilization of Proximal Tibia Shaft Fracture: A Case Report
Authors: Derbas Jawad Nouraldeen Khader , Moghamis Isam Sami , Mudawi Aiman , Alam Syed , Ameen Basim Shaman
Published: December 2022

Compartment syndrome secondary to pseudoaneurysm formation following surgical stabilization of tibia shaft fracture is a rare entity. Early recognition as early as possible can prevent associated morbidities and significant disabilities by surgical decompression of leg compartments. A 56-year-old male patient presented to our clinic during his routine postsurgical follow-up with a progressive painful right leg swelling, which progressed over 2 months following right tibia shaft stabilization secondary to a road traffic accident. The patient underwent further investigation of this swelling. After infection was ruled out, it was found to be a pseudoaneurysm. Following diagnosis, the patient underwent endovascular coiling of the pseudoaneurysm feeding vessel, and surgical decompression with evacuation of the hematoma was performed. Multiple causes for compartment syndrome do exist; pseudoaneurysm is different from other causes in that it has a feeding vessel. Careful preoperative endovascular coiling is important to prevent and control intraoperative bleeding, which prevents further development of compartment syndrome. Moreover, aggressive postoperative physiotherapy should be avoided in the early period, especially soft tissue manipulation, as this might be a leading cause for the development of such a condition.
A Report of Unusual Case of Acquired Dermal Melanocytosis on the Scalp of a Caucasian Man with a Literature Review
Authors: Mohaghegh Fatemeh , Rajabi Parvin , Nabavinejad Samin , Tavousi Tabatabaei Elham
Published: December 2022

Dermal melanocytosis includes several benign pigmented lesions which present as blue-gray color which is a result of the color transmission of melanin pigment through the dermis. While some types are present at birth, there is an acquired variant, acquired dermal melanocytosis (ADM), which usually involves faces of middle-aged Asian women. To the best of our knowledge, there are limited reports of extra facial ADM which all are on the trunk and extremities. Herein, we report a unique case of extra facial ADM affecting the scalp of a middle-aged man and provide a review of all extra facial ADM cases that have been reported.
Valve‐in‐Valve Transcatheter Aortic Valve Replacement Versus Redo Surgical Aortic Valve Replacement for Failed Surgical Aortic Bioprostheses: A Systematic Review and Meta‐Analysis
Authors: Raschpichler Matthias , de Waha Suzanne , Holzhey David , Schwarzer Guido , Flint Nir , Kaewkes Danon , Bräuchle Paul T. , Dvir Danny , Makkar Raj , Ailawadi Gorav , Abdel‐Wahab Mohamed , Thiele Holger , Borger Michael A.
Published: December 2022

Background

In the absence of randomized controlled trials, reports from nonrandomized studies comparing valve‐in‐valve implantation (ViV) to redo surgical aortic valve replacement (rAVR) have shown inconsistent results.

Methods and Results

PubMed/MEDLINE, Google Scholar, and CENTRAL (Cochrane Central Register of Controlled Trials) were searched through December 2021. Meta‐Analysis of Observational Studies in Epidemiology guidelines were followed. The protocol was registered at the International Prospective Register of Systematic Reviews. Random effects models were applied. The primary outcomes of interest were short‐term and midterm mortality. Secondary outcomes included stroke, myocardial infarction, acute renal failure, and permanent pacemaker implantation, as well as prosthetic aortic valve regurgitation, mean transvalvular gradient, and severe prosthesis‐patient mismatch. Of 8881 patients included in 15 studies, 4458 (50.2%) underwent ViV and 4423 (49.8%) rAVR. Short‐term mortality was 2.8% in patients undergoing ViV compared with 5.0% in patients undergoing rAVR (risk ratio [RR] 0.55 [95% CI, 0.34–0.91],
P
=0.02). Midterm mortality did not differ in patients undergoing ViV compared with patients undergoing rAVR (hazard ratio, 1.27 [95% CI, 0.72–2.25]). The rate of acute kidney failure was lower following ViV, (RR, 0.54 [95% CI, 0.33–0.88],
P
=0.02), whereas prosthetic aortic valve regurgitation (RR, 4.18 [95% CI, 1.88–9.3],
P
=0.003) as well as severe patient–prothesis mismatch (RR, 3.12 [95% CI, 2.35–4.1],
P
<0.001) occurred more frequently. The mean transvalvular gradient was higher following ViV (standard mean difference, 0.44 [95% CI, 0.15–0.72],
P
=0.008). There were no significant differences between groups with respect to stroke (
P
=0.26), myocardial infarction (
P
=0.93), or pacemaker implantation (
P
=0.21).

Conclusions

Results of this meta‐analysis demonstrate better short‐term mortality after ViV compared with rAVR. Midterm mortality was similar between groups. Given the likely selection bias in these individual reports, an adequately powered multicenter randomized clinical trial with sufficiently long follow‐up in patients with low‐to‐intermediate surgical risk is warranted.

Registration

URL:
crd.york.ac.uk/prospero/
. Unique identifier: CRD42021228752.
Risk and Subtypes of Stroke Following New‐Onset Postoperative Atrial Fibrillation in Coronary Bypass Surgery: A Population‐Based Cohort Study
Authors: Feilberg Rasmussen Louise , Andreasen Jan J. , Riahi Sam , Lundbye‐Christensen Søren , Johnsen Søren P. , Andersen Grethe , Mortensen Janne K.
Published: December 2022

Background

New‐onset postoperative atrial fibrillation (POAF) develops in approximately one‐third of patients undergoing cardiac surgery and is associated with a higher incidence of ischemic stroke and increased mortality. However, it remains unknown to what extent ischemic stroke events in patients with POAF are cardioembolic and whether anticoagulant therapy is indicated. We investigated the long‐term risk and pathogenesis of postoperative stroke in patients undergoing coronary artery bypass grafting experiencing POAF.

Methods and Results

This was a register‐based cohort study. Data from the WDHR (Western Denmark Heart Registry) were linked with the DNPR (Danish National Patient Register), the Danish National Prescription Register, and the Cause of Death Register. All stroke diagnoses were verified, and ischemic stroke cases were subclassified according to pathogenesis. Furthermore, investigations of all‐cause mortality and the use of anticoagulation medicine for the individual patient were performed. A total of 7813 patients without a preoperative history of atrial fibrillation underwent isolated coronary artery bypass grafting between January 1, 2010, and December 31, 2018, in Western Denmark. POAF was registered in 2049 (26.2%) patients, and a postoperative ischemic stroke was registered in 195 (2.5%) of the patients. After adjustment, there was no difference in the risk of ischemic stroke (hazard ratio [HR], 1.08 [95% CI, 0.74–1.56]) or all‐cause mortality (HR, 1.09 [95% CI, 0.98–1.23]) between patients who developed POAF and non‐POAF patients. Although not statistically significant, patients with POAF had a higher incidence rate (IR; per 1000 patient‐years) of cardioembolic stroke (IR, 1 [95% CI, 0.6–1.6] versus IR, 0.5 [95% CI, 0.3–0.8]), whereas non‐POAF patients had a higher incidence rate of large‐artery occlusion stroke (IR, 1.1 [95% CI, 0.8–1.5] versus IR, 0.7 [95% CI, 0.4–1.4]). Early initiation of anticoagulation medicine was not associated with a lower risk of ischemic stroke. However, patients with POAF were more likely to die of cardiovascular causes than non‐POAF patients (
P
<0.001).

Conclusions

We found no difference in the adjusted risk of postoperative stroke or all‐cause mortality in POAF versus non‐POAF patients. Patients with POAF after coronary artery bypass grafting presented with a higher, although not significant, proportion of ischemic strokes of the cardioembolic type.
Performance of the American Heart Association/American College of Cardiology Guideline‐Recommended Pretest Probability Model for the Diagnosis of Obstructive Coronary Artery Disease
Authors: Winther Simon , Murphy Theodore , Schmidt Samuel Emil , Bax Jeroen J. , Wijns William , Knuuti Juhani , Bøttcher Morten
Published: December 2022

Background

Substantial differences exist between different guideline‐recommended pretest probability (PTP) models for the detection of obstructive coronary artery disease (CAD). This study was performed to study the performance of the 2021 American Heart Association/American College of Cardiology (AHA/ACC) guideline‐recommended PTP (AHA/ACC‐PTP) model in assessing the likelihood of obstructive CAD compared with previously proposed models.

Methods and Results

Symptomatic patients (N=50 561) referred for coronary computed tomography angiography were included. The reference standard was invasive coronary angiography with optional fractional flow reserve measurements. The AHA/ACC‐PTP values based on sex and age were calculated and compared with the 2019 European Society of Cardiology guideline PTP values based on sex, age, and symptoms as well as the risk factor–weighted clinical likelihood values based on sex, age, symptoms, and risk factors. The AHA/ACC‐PTP maximum values overestimated by a factor of 2.6 the actual prevalence of CAD. Compared with the AHA/ACC‐PTP model (area under the receiver‐operating curve, 71.5 [95% CI, 70.7–72.2]), inclusion of typicality of symptoms in the European Society of Cardiology guideline PTP improved discrimination of CAD (area under the receiver‐operating curve, 75.5 [95% CI, 74.7–76.3]). Inclusion of both symptoms and risk factors in the risk factor–weighted clinical likelihood model further improved discrimination (area under the receiver‐operating curve, 77.7 [95% CI, 77.0–78.5]). The proportion of patients classified as very low PTP was lower using the AHA/ACC‐PTP (5%) compared with the European Society of Cardiology guideline PTP (19%) and the risk factor–weighted clinical likelihood (49%) models.

Conclusions

The new AHA/ACC‐PTP model overestimates the prevalence of obstructive CAD substantially if type of symptoms and risk factors are not taken into account. Inclusion of both symptoms and risk factors improves model performance and identifies more patients with very low likelihood of CAD in whom further testing can be deferred.
Depression and Anxiety Are Associated With Cardiovascular Health in Young Adults
Authors: Patterson Sierra L. , Marcus Michele , Goetz Margarethe , Vaccarino Viola , Gooding Holly C.
Published: December 2022

Background

Cardiovascular health (CVH) declines in young adulthood, and mood disorders commonly emerge during this life stage. This study examined the association between depression, anxiety, and CVH metrics among young adults.

Methods and Results

We conducted a cross‐sectional analysis of participants aged 18 to 34 years who completed the Emory Healthy Aging Study Health History Questionnaire (n=875). We classified participants as having poor, intermediate, or ideal levels of the 8 CVH metrics using definitions set forth by the American Heart Association with adaptions when necessary. We defined depression and anxiety as absent, mild, or moderate to severe using standard cutoffs for Patient Health Questionnaire and General Anxiety Disorder scales. We used multivariable regression to examine the association between depression and anxiety and CVH, adjusting for age, sex, race and ethnicity, income, and education. The mean participant age was 28.3 years, and the majority identified as women (724; 82.7%); 129 (14.7%) participants had moderate to severe anxiety, and 128 (14.6%) participants had moderate to severe depression. Compared with those without anxiety, participants with moderate to severe anxiety were less likely to meet ideal levels of physical activity (adjusted prevalence ratio [aPR], 0.60 [95% CI, 0.44–0.82]), smoking (aPR, 0.90 [95% CI, 0.82–0.99]), and body mass index (aPR, 0.79 [95% CI, 0.66–0.95]). Participants with moderate to severe depression were less likely than those without depression to meet ideal levels of physical activity (aPR, 0.48 [95% CI, 0.34–0.69]), body mass index (aPR, 0.75 [95% CI, 0.61–0.91]), sleep (aPR, 0.79 [95% CI, 0.66–0.94]), and blood pressure (aPR, 0.92 [95% CI, 0.86–0.99]).

Conclusions

Anxiety and depression are associated with less ideal CVH in young adults. Interventions targeting CVH behaviors such as physical activity, diet, and sleep may improve both mood and CVH.
Recruitment in Acute Stroke Trials: Challenges and Potential Solutions
Authors: Broderick Joseph P. , Aziz Yasmin N. , Adeoye Opeolu M. , Grotta James C. , Naidech Andrew M. , Barreto Andrew D. , Derdeyn Colin P. , Sucharew Heidi J. , Elm Jordan J. , Khatri Pooja
Published: December 2022

Randomized clinical trials of acute stroke have led to major advances in acute stroke therapy over the past decade. Despite these successes, recruitment in acute trials is often difficult. We outline challenges in recruitment for acute stroke trials and present potential solutions, which can increase the speed and decrease the cost of identifying new treatments for acute stroke. One of the largest opportunities to increase the speed of enrollment and make trials more generalizable is expansion of inclusion criteria whose impact on expected recruitment can be assessed by epidemiologic and registry databases. Another barrier to recruitment besides the number of eligible patients is availability of study investigators limited to business hours, which may be helped by financial support for after-hours call. The wider use of telemedicine has accelerated quicker stroke treatment at many hospitals and has the potential to accelerate research enrollment but requires training of clinical investigators who are often inexperienced with this approach. Other potential solutions to enhance recruitment include rapid prehospital notification of clinical investigators of potential patients, use of mobile stroke units, advances in the process of emergency informed consent, storage of study medication in the emergency department, simplification of study treatments and data collection, education of physicians to improve equipoise and enthusiasm for randomization of patients within a trial, and clear recruitment plans, and even potentially coenrollment, when there are competing trials at sites. Without successful recruitment, scientific advances and clinical benefit for acute stroke patients will lag.
The neutrophil-lymphocyte ratio to predict poor prognosis of critical acute myocardial infarction patients
Authors: Li Xinming , Che Lin , Wang Wenhui , Liu Linlin , Ning Zhongping
Published: December 2022

IntroductionInflammation is closely related to adverse outcomes of acute myocardial infarction (AMI). This study aimed to evaluate whether neutrophil-lymphocyte ratio (NLR) can predict poor prognosis of critical AMI patients.
Materials and methodsWe designed a retrospective cohort study and extracted AMI patients from the “Medical Information Mart for Intensive Care-III” database. The primary outcome was 1-year all-cause mortality. The secondary outcomes were 90-day and in-hospital all-cause mortalities, and acute kidney injury (AKI) incidence. The optimal cut-offs of NLR were picked by X-tile software according to the 1-year mortality and patient groups were created: low-NLR (< 4.8), high-NLR (4.8 - 21.1), and very high-NLR (> 21.1). Cox and modified Poisson regression models were used to evaluate the effect of NLR on outcomes in critically AMI patients.
ResultsFinally, 782 critical AMI patients were enrolled in this study, and the 1-year mortality was 32% (249/782). The high- and very high-NLR groups had a higher incidence of outcomes than the low-NLR group (P < 0.05). The multivariate regression analyses found that the high- and very high-NLR groups had a higher risk of 1-year mortality (Hazard ratio (HR) = 1.59, 95% CI: 1.12 to 2.24, P = 0.009 and HR = 1.73, 95% CI: 1.09 to 2.73, P = 0.020), 90-day mortality (HR = 1.69, 95% CI: 1.13 to 2.54, P = 0.011 and HR = 1.90, 95% CI: 1.13 to 3.20, P = 0.016), in-hospital mortality (Relative risk (RR) = 1.77, 95% CI: 1.14 to 2.74, P = 0.010 and RR = 2.10, 95% CI: 1.23 to 3.58, P = 0.007), and AKI incidence (RR = 1.44, 95% CI: 1.06 to 1.95, P = 0.018 and RR = 1.34, 95% CI: 0.87 to 2.07, P = 0.180) compared with low-NLR group. NLR retained stable predictive ability in sensitivity analyses.
ConclusionBaseline NLR is an independent risk factor for 1-year mortality, 90-day mortality, in-hospital mortality, and AKI incidence in AMI patients.