bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantization of locally compact groups associated with essentially bijective 1-cocycles
Authors: Bieliavsky Pierre , Gayral Victor , Neshveyev Sergey , Tuset Lars
Published: March 2024

Given an extension [Formula: see text] of locally compact groups, with [Formula: see text] abelian, and a compatible essentially bijective [Formula: see text]-cocycle [Formula: see text], we define a dual unitary [Formula: see text]-cocycle on [Formula: see text] and show that the associated deformation of [Formula: see text] is a cocycle bicrossed product defined by a matched pair of subgroups of [Formula: see text]. We also discuss an interpretation of our construction from the point of view of Kac cohomology for matched pairs. Our setup generalizes that of Etingof and Gelaki for finite groups and its extension due to Ben David and Ginosar, as well as our earlier work on locally compact groups satisfying the dual orbit condition. In particular, we get a locally compact quantum group from every involutive nondegenerate set-theoretical solution of the Yang–Baxter equation, or more generally, from every brace structure. On the technical side, the key new points are constructions of an irreducible projective representation of [Formula: see text] on [Formula: see text] and a unitary quantization map [Formula: see text] of Kohn–Nirenberg type.
DHONE: Density-based higher-order network embedding
Authors: Guan Wei , Guan Qing , Duan Yueran
Published: March 2024

Studies have indicated that focusing solely on pairwise interactions between two nodes disregards the associativity among multi-nodes in the network’s local structure. This associativity can be seen as dependencies among nodes, where certain edges’ presence depends on the path leading to it. Examinations on diverse datasets have approved that the variable order of chained dependencies allows for the preservation of structure information, which enables the reconstruction of the original network into a Higher-Order Network (HON) with improved quality of network representation. This paper proposes a Density-based Higher-Order Network Embedding (DHONE) algorithm, which integrates the concept of higher-order density into the network-embedding process in order to classify the contribution of different orders of dependencies. Through the construction of a novel and effective higher-order adjacency matrix, DHONE steadily improves the accuracy of network representation learning. Experimental results demonstrate DHONEs proficiency in improving embedding accuracy and overall algorithm robustness. Furthermore, grounded in the concept of higher-order density proposed herein, numerous dependencies have been discerned within the network generated from trajectories, potentially indicating the role of multi-node structures in networks.
Numerical analyses of M31 dark matter profiles
Authors: Boshkayev Kuantay , Konysbayev Talgar , Kurmanov Yergali , Luongo Orlando , Muccino Marco , Quevedo Hernando , Zhumakhanova Gulnur
Published: March 2024

In this paper, we reproduce the rotation curve of the Andromeda galaxy (M31) by taking into account its bulge, disk and halo components, considering the last one to contain the major part of dark matter mass. Hence, our prescription is to split the galactic bulge into two components, namely, the inner and main bulges, respectively. Both bulges are thus modeled by exponential density profiles since we underline that the widely accepted de Vaucouleurs law fails to reproduce the whole galactic bulge rotation curve. In addition, we adopt various well-known phenomenological dark matter profiles to estimate the dark matter mass in the halo region. Moreover, we apply the least-squares fitting method to determine from the rotation curve the model free parameters, namely, the characteristic (central) density, scale radius and consequently the total mass. To do so, we perform Markov chain Monte Carlo statistical analyses based on the Metropolis algorithm, maximizing our likelihoods adopting velocity and radii data points of the rotation curves. We do not fit separately the components for bulges, disk and halo, but we perform an overall fit including all the components and employing all the data points. Thus, we critically analyze our corresponding findings and, in particular, we employ the Bayesian information criterion to assess the most accredited model to describe M31 dark matter dynamics.
Shadowing, Hyers–Ulam stability and hyperbolicity for nonautonomous linear delay differential equations
Authors: Backes Lucas , Dragičević Davor , Pituk Mihály
Published: March 2024

It is known that hyperbolic nonautonomous linear delay differential equations in a finite dimensional space are Hyers–Ulam stable and hence shadowable. The converse result is available only in the special case of autonomous and periodic linear delay differential equations with a simple spectrum. In this paper, we prove the converse and hence the equivalence of all three notions in the title for a general class of nonautonomous linear delay differential equations with uniformly bounded coefficients. The importance of the boundedness assumption is shown by an example.
Sharp spectral gap estimates for higher-order operators on Cartan–Hadamard manifolds
Authors: Farkas Csaba , Kajántó Sándor , Kristály Alexandru
Published: March 2024

The goal of this paper is to provide sharp spectral gap estimates for problems involving higher-order operators (including both the clamped and buckling plate problems) on Cartan–Hadamard manifolds. The proofs are symmetrization-free — thus no sharp isoperimetric inequality is needed — based on two general, yet elementary functional inequalities. The spectral gap estimate for clamped plates solves a sharp asymptotic problem from [Q.-M. Cheng and H. Yang, Universal inequalities for eigenvalues of a clamped plate problem on a hyperbolic space, Proc. Amer. Math. Soc. 139(2) (2011) 461–471] concerning the behavior of higher-order eigenvalues on hyperbolic spaces, and answers a question raised in [A. Kristály, Fundamental tones of clamped plates in nonpositively curved spaces, Adv. Math. 367(39) (2020) 107113] on the validity of such sharp estimates in high-dimensional Cartan–Hadamard manifolds. As a byproduct of the general functional inequalities, various Rellich inequalities are established in the same geometric setting.
Pseudoconvex submanifolds in Kähler 4-manifolds
Authors: Weber Brian
Published: March 2024

This paper shows how a Levi-flat or pseudoconvex submanifold in a Kähler 4-manifold restricts the ambient manifold’s topology and its geometry at infinity.
Embedding Hamiltonian Paths with Prescribed Linear Forests into k-ary n-Cube Networks
Authors: Meng Kaiyue , Yang Yuxing
Published: March 2024

Graph embedding is a fundamental problem in computer science. Let [Formula: see text] (resp., [Formula: see text]) be the interconnection network for a parallel computer system [Formula: see text] (resp., [Formula: see text]). If [Formula: see text] could be embedded into [Formula: see text], then [Formula: see text] can simulate [Formula: see text]’s behavior. The [Formula: see text]-ary [Formula: see text]-cube [Formula: see text] is a node-symmetric and link-symmetric recursive interconnection network for parallel computer systems. Let [Formula: see text] be a prescribed linear forest of [Formula: see text], and let [Formula: see text] and [Formula: see text] be any two distinct nodes in [Formula: see text] such that [Formula: see text] has no path with [Formula: see text] or [Formula: see text] as internal nodes, or both as end-nodes. This paper shows that there is a Hamiltonian path passing through [Formula: see text] between [Formula: see text] and [Formula: see text] in [Formula: see text] with [Formula: see text] and odd [Formula: see text] even if the number of links in [Formula: see text] is up to [Formula: see text].
Synergistic Strategy of Sustainable Hospital Site Selection in Saudi Arabia Using Spherical Fuzzy MCDM Methodology
Authors: Gazi Kamal Hossain , Momena Alaa Fouad , Salahshour Soheil , Mondal Sankar Prasad , Ghosh Arijit
Published: March 2024

Site selection for a hospital is demanding and challenging work. It’s become more complicated when considering various infectious diseases. Multiple criteria and sub-criteria are considered for selecting the most suitable and efficient hospital location. In this paper, we find the most suitable location for multiple disease-related hospitals using the multi-criteria decision-making (MCDM) methodologies. The proposed study is done by the MCDM techniques, namely spherical Entropy and spherical VIekriterijumsko KOmpromisno Rangiranje (VIKOR) methods. The decision-making for site selection is based on multiple experts’ opinions. Also, we use real data sources in spherical fuzzy numbers (SFN) to capture all its uncertainty. We proposed a new score function and an accuracy function of the SFN to evaluate crisp value from fuzzy numbers. The most prioritized criteria and sub-criteria are determined with their weights. We optimized the proposed site based on demand and criterion weight. Finally, sensitivity analysis and comparative analysis are conducted to check the stability and robustness of the result.
Protein Interaction and Molecular Docking Analysis by Schiff Base Derived from 2,4-Dinitro Phenyl Hydrazine
Authors: Rana Tapan K. , Mohanty Patitapaban , Dash Pragyan P. , Mohapatra Priyaranjan , Barick Aruna K. , Jena Pradip K. , Behera Lingaraj , Jali Bigyan R.
Published: March 2024

A novel and cost-effective 2,4-dinitrophenyl hydrazine derived from Schiff base 1-benzylidine-2-(2,4-dinitrophenyl) hydrazine ( L) was designed and characterized using various spectroscopic techniques. The interaction between L and bovine serum albumin (BSA) has been carried out using UV–Vis and fluorescence spectroscopy, DSC, SEM, and molecular docking methods. The phosphate buffer ([Formula: see text]) solution of BSA showed fluorescence emission maxima at 342[Formula: see text]nm. Upon addition of L to the BSA solution, it quenched the fluorescence emission at 342[Formula: see text]nm. The quenching of the fluorescence emission is due to the formation of a complex between L and BSA. The binding constant was calculated from the fluorescence titrations and found to be [Formula: see text][Formula: see text]M[Formula: see text]. Further, molecular docking analysis was carried out to establish the binding between L and BSA.
Adaptive Content-Aware Influence Maximization via Online Learning to Rank
Authors: Theocharidis Konstantinos , Karras Panagiotis , Terrovitis Manolis , Skiadopoulos Spiros , Lauw Hady W.
Published: March 2024

How can we adapt the composition of a post over a series of rounds to make it more appealing in a social network? Techniques that progressively learn how to make a
fixed
post more influential over rounds have been studied in the context of the
Influence Maximization
(IM) problem, which seeks a set of
seed users
that maximize a post’s influence. However, there is no work on progressively learning how a post’s
features
affect its influence. In this article, we propose and study the problem of
Adaptive Content-Aware Influence Maximization
(ACAIM), which calls to find
k
features to form a post in each round so as to maximize the cumulative influence of those posts over all rounds. We solve ACAIM by applying, for the first time, an
Online Learning to Rank
(OLR) framework for IM purposes. We introduce the CATRID
propagation model
, which expresses how posts disseminate in a social network using click probabilities and post visibility criteria and develop a
simulator
that runs CATRID via a training-testing scheme based on real posts of the VK social network, so as to realistically represent the learning environment. We deploy three
learners
that solve ACAIM in an online (real-time) manner. We experimentally prove the practical suitability of our solutions via exhaustive experiments on multiple brands (operating as different
case studies
) and several VK datasets; the best learner is evaluated on 45 separate
case studies
yielding convincing results.
SARI: Shared Autonomy across Repeated Interaction
Authors: Jonnavittula Ananth , Mehta Shaunak A. , Losey Dylan P.
Published: March 2024

Assistive robot arms try to help their users perform everyday tasks. One way robots can provide this assistance is
shared autonomy
. Within shared autonomy, both the human and robot maintain control over the robot’s motion: as the robot becomes confident it understands what the human wants, it intervenes to automate the task. But how does the robot know these tasks in the first place? State-of-the-art approaches to shared autonomy often rely on prior knowledge. For instance, the robot may need to know the human’s potential goals beforehand. During long-term interaction these methods will inevitably break down—sooner or later the human will attempt to perform a task that the robot does not expect. Accordingly, in this article we formulate an alternate approach to shared autonomy that learns assistance from scratch. Our insight is that operators
repeat
important tasks on a daily basis (e.g., opening the fridge, making coffee). Instead of relying on prior knowledge, we therefore take advantage of these repeated interactions to learn assistive policies. We introduce SARI, an algorithm that
recognizes
the human’s task,
replicates
similar demonstrations, and
returns
control when unsure. We then combine learning with control to demonstrate that the error of our approach is uniformly ultimately bounded. We perform simulations to support this error bound, compare our approach to imitation learning baselines, and explore its capacity to assist for an increasing number of tasks. Finally, we conduct three user studies with industry-standard methods and shared autonomy baselines, including a pilot test with a disabled user. Our results indicate that learning shared autonomy across repeated interactions matches existing approaches for known tasks and outperforms baselines on new tasks. See videos of our user studies here:
https://youtu.be/3vE4omSvLvc
.
Acidithiobacillus ferrooxidans Leaching of Silica‐Sulfide Gold Ores from May‐Hibey Deposits, Tigray, Ethiopia
Authors: Berhe Goitom Gebreyohannes , Sbhatu Desta Berhe , Gebre Samuel Estifanos , Abay Kiros Hagos , Mhretu Genet Gebryohannes , Tesfamariam Gebrekidan Mebrahtu , Lapiso Samuel Alemayehu , Cheru Mulugeta Sisay , Meressa Afewerk Gebre
Published: March 2024

Oxidative leaching is an inexpensive alternative to using chemical cyanide extraction methods for gold from low‐grade gold sulfide. Oxidation of finely ground gold‐bearing ore by Acidithiobacillus ferrooxidans was evaluated in terms of cell density, pH, and leaching efficiency of Fe and Au in shake flask experiments. The compositional and elemental analyses of the beneficiated ore were analyzed using XRD and EDXRF spectroscopy. The ore’s primary constituents are gold (4.356 mg/L), silicon, iron, and sulfur (62.456, 15.441, and 7.912 wt%, respectively). XRD spectra, the main phases of the concentrated ore, showed that the major components of the ore were quartz, syn, silicon sulfide, pyrite, and polymetallic elements such as silderenrite, gismondine, siderenikite, hematite, and syn. The experimental results, with Acidithiobacillus ferrooxidans bacteria and blank, were evaluated. The pH of the blank remained nearly constant, and the pH of the bioleached was occasionally lowered. The A. ferrooxidans strain always grew better throughout the bioleaching process. For the A. ferrooxidans strain, the cell density of cells reached a maximum of 90.00 × 106 cells/mL after the 11th week and decreased to 87.00 × 106 cells/mL after the 12th week. The decrease in cell density may be due to the presence of polymetallic elements such as Al, Cr, Ti, and Ni, leading to reduced metal tolerance of the A. ferrooxidans strain. In the A. ferrooxidans leaching process, the maximum total iron and gold extraction reached 92.16% (14.23 mg/L) and 99.97% (4.355 ppm), respectively, after the 11th week, and leaching tends to decrease up to 14 weeks, which may be due to the formation of secondary minerals. More research will be performed to optimize the procedure and leaching kinetic, examine the impact of metal content, and take into account the potential for bioleaching process pollution in addition to the amount of gold recovered.
Multistrategy Fusion Particle Swarm for Dynamic Economic Dispatch Optimization of Renewable Energy Sources
Authors: Li Yueying , Wu Feng
Published: March 2024

This paper presents a multistrategy fusion particle swarm optimization model for dynamic economic dispatching of renewable energy in distribution networks. The objective is to minimize active network losses and system voltage deviation while considering the integration of distributed energy sources and static reactive power compensators. The algorithm incorporates specific strategies, including a particle position change strategy based on the midpipeline convergence approach, a strategy for generating exploding particles near the optimal particles, and a particle velocity update strategy relying on the global optimal particle position. The inertia weights and particle position update methods of the simplified particle swarm optimization algorithm are also utilized. Simulation experiments are conducted on an IEEE 33 bus radial distribution system, demonstrating the effective optimization of system losses while ensuring system voltage stability. This research contributes to the scientific understanding of renewable energy integration in distribution networks and its economic dispatching.
Effect of Nurse Proactive Behavior on Patient Education for Fall Prevention in Acute Settings: A Moderated-Mediation Model
Authors: Vechter Tamar , Drach-Zahavy Anat
Published: March 2024

Introduction. Falls among hospitalized patients continue to pose a serious threat to patient safety worldwide. Effective fall-prevention education is considered vital for fall prevention. Nurses’ resilience and proactivity may improve the fall-prevention education nurses provide to patients, but how to motivate nurses’ proactivity remains unsolved. This study aimed to examine whether (1) nurse’s resilience and social capital are jointly associated with nurse proactivity and (2) adherence to procedures further moderates the relationships between nurse proactivity and the fall prevention education provided to patients by the nurse. Methods. A nested (∼3 patients per nurse) cross-sectional observational design has been employed in this study. 101 bedside registered nurses were recruited from fourteen internal and surgical wards at a medium-size hospital. For each nurse, ∼3 of their newly admitted patients were recruited (total of 271 patients). Nurses completed validated questionnaires on personal resilience, social capital, following procedures, and sociodemographic data. Fall-prevention education was assessed via a short-structured interview with patients. Hypotheses were analyzed using the Hayes PROCESS macro. Results. Social capital, nurse resilience, and their interaction were associated with proactive behavior. Proactive behavior, adherence to procedures, and their interaction (β = −0.57, p<0.01) were associated with patient education for fall prevention given by nurses. The moderated-mediation model was significant under medium and high levels of social capital and low levels of adherence to procedures. Conclusion. The study highlights the importance of nurse proactivity in educating patients about fall prevention, especially when adherence to procedures in the ward is perceived as low. Furthermore, nurses’ proactivity can be promoted by nurturing both their resilience and their social capital. Nursing managers should nurture proactivity at the work environment of the 21-century, by fostering resilience and enculturing social capital. Concomitantly, employees should be educated at ways to promote personal resilience and engage in wise proactivity.
Figure 5 from The Next-Generation Oral Selective Estrogen Receptor Degrader Camizestrant (AZD9833) Suppresses ER+ Breast Cancer Growth and Overcomes Endocrine and CDK4/6 Inhibitor Resistance
Authors: Lawson Mandy , Cureton Natalie , Ros Susana , Cheraghchi-Bashi Azadeh , Urosevic Jelena , D'Arcy Sophie , Delpuech Oona , DuPont Michelle , Fisher David I. , Gangl Eric T. , Lewis Hilary , Trueman Dawn , Wali Neha , Williamson Stuart C. , Moss Jennifer , Montaudon Elodie , Derrien Heloise , Marangoni Elisabetta , Miragaia Ricardo J. , Gagrica Sladjana , Morentin-Gutierrez Pablo , Moss Thomas A. , Maglennon Gareth , Sutton Daniel , Polanski Radoslaw , Rosen Alan , Cairns Jonathan , Zhang Pei , Sánchez-Guixé Mònica , Serra Violeta , Critchlow Susan E. , Scott James S. , Lindemann Justin P.O. , Barry Simon T. , Klinowska Teresa , Morrow Christopher J. , Carnevalli Larissa S.
Published: March 2024

Enhanced efficacy of camizestrant in combination with PI3K/AKT/mTOR inhibitors as doublets in CDK4/6-sensitive and -resistant models (1). A–D, Combination of camizestrant with PI3Kα inhibitor alpelisib (A), mTOR inhibitor everolimus (B), AKT inhibitor capivasertib (C), or CDK4/6 inhibitor palbociclib (D) delivers enhanced efficacy compared with monotherapy in D538G ESR1m PDX CTC-174. Statistical analysis was performed by one-tailed, unequal variance t test versus log (change in tumor volume) compared with vehicle control at the final day of treatment. E, Relative tumor volume plots of ST3632 PDX model treated with oral camizestrant at 10 mg/kg daily, oral palbociclib at 50 mg/kg daily, and oral abemaciclib 50 mg/kg daily, and with camizestrant + abemaciclib and camizestrant + palbociclib. Statistical analysis was performed by one-tailed, unequal variance t test versus log (change in tumor volume) at the final day of treatment. F,In vivo combination of camizestrant at 10 mg/kg daily with palbociclib 50 mg/kg, abemaciclib 50 mg/kg, and capivasertib 130 mg/kg in PDX ST1799 dosed for 40 days (gray area). For clarity, the graph is divided into four subgraphs due to the large number of treatment arms; where they appear, the vehicle, camizestrant, and palbociclib arms are the same in each subgraph. CDK, cyclin-dependent kinase. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; ns, not significant.
Phase I/II Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors
Authors: Corcoran Ryan B. , Do Khanh T. , Kim Jeong E. , Cleary James M. , Parikh Aparna R. , Yeku Oladapo O. , Xiong Niya , Weekes Colin D. , Veneris Jennifer , Ahronian Leanne G. , Mauri Gianluca , Tian Jun , Norden Bryanna L. , Michel Alexa G. , Van Seventer Emily E. , Siravegna Giulia , Camphausen Kyle , Chi Gary , Fetter Isobel J. , Brugge Joan S. , Chen Helen , Takebe Naoko , Penson Richard T. , Juric Dejan , Flaherty Keith T. , Sullivan Ryan J. , Clark Jeffrey W. , Heist Rebecca S. , Matulonis Ursula A. , Liu Joyce F. , Shapiro Geoffrey I.
Published: March 2024

Purpose:

MEK inhibitors (MEKi) lack monotherapy efficacy in most RAS-mutant cancers. BCL-xL is an anti-apoptotic protein identified by a synthetic lethal shRNA screen as a key suppressor of apoptotic response to MEKi.

Patients and Methods:

We conducted a dose escalation study (NCT02079740) of the BCL-xL inhibitor navitoclax and MEKi trametinib in patients with RAS-mutant tumors with expansion cohorts for: pancreatic, gynecologic (GYN), non–small cell lung cancer (NSCLC), and other cancers harboring KRAS/NRAS mutations. Paired pretreatment and day 15 tumor biopsies and serial cell-free (cf)DNA were analyzed.

Results:

A total of 91 patients initiated treatment, with 38 in dose escalation. Fifty-eight percent had ≥3 prior therapies. A total of 15 patients (17%) had colorectal cancer, 19 (11%) pancreatic, 15 (17%) NSCLC, and 32 (35%) GYN cancers. The recommended phase II dose (RP2D) was established as trametinib 2 mg daily days 1 to 14 and navitoclax 250 mg daily days 1 to 28 of each cycle. Most common adverse events included diarrhea, thrombocytopenia, increased AST/ALT, and acneiform rash. At RP2D, 8 of 49 (16%) evaluable patients achieved partial response (PR). Disease-specific differences in efficacy were noted. In patients with GYN at the RP2D, 7 of 21 (33%) achieved a PR and median duration of response 8.2 months. No PRs occurred in patients with colorectal cancer, NSCLC, or pancreatic cancer. MAPK pathway inhibition was observed in on-treatment tumor biopsies. Reductions in KRAS/NRAS mutation levels in cfDNA correlated with clinical benefit.

Conclusions:

Navitoclax in combination with trametinib was tolerable. Durable clinical responses were observed in patients with RAS-mutant GYN cancers, warranting further evaluation in this population.
Supplementary Methods from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Supplementary methods
Supplementary Figure 21 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Survival probability of head and neck cancer
Supplementary Figure 17 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Subcutaneous xenograft tumor formation in nude (NSG) mice
Supplementary Figure 16 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Control, GAN siRNA and GAN overexpression effect on transcription factors in ME180 and HeLa cell lines
Supplementary Figure 14 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Snapshot view of exon 8 in ME180 and GAN edited cell lines
Do Antibiotic-Impregnated Envelopes Prevent Deep Brain Stimulation Implantable Pulse Generator Infections? A Prospective Cohort Study
Authors: Colditz Michael , Heard Tomas , Silburn Peter , Coyne Terry
Published: March 2024

Introduction: Infection after deep brain stimulation (DBS) implanted pulse generator (IPG) replacement is uncommon but when it occurs can cause significant clinical morbidity, often resulting in partial or complete DBS system removal. An antibiotic absorbable envelope developed for cardiac implantable electronic devices (IEDs), which releases minocycline and rifampicin for a minimum of 7 days, was shown in the WRAP-IT study to reduce cardiac IED infections for high-risk cardiac patients. We aimed to assess whether placing an IPG in the same antibiotic envelope at the time of IPG replacement reduced the IPG infection rate. Methods: Following institutional ethics approval (UnitingCare HREC), patients scheduled for IPG change due to impending battery depletion were prospectively randomised to receive IPG replacement with or without an antibiotic envelope. Patients with a past history of DBS system infection were excluded. Patients underwent surgery with standard aseptic neurosurgical technique [J Neurol Sci. 2017;383:135–41]. Subsequent infection requiring antibiotic therapy and/or IPG removal or revision was recorded. Results: A total of 427 consecutive patients were randomised from 2018 to 2021 and followed for a minimum of 12 months. No patients were lost to follow-up. At the time of IPG replacement, 200 patients received antibiotic envelope (54 female, 146 male, mean age 72 years), and 227 did not (43 female, 184 male, mean age 71 years). The two groups were homogenous for risk factors of infection. The IPG replacement infection rate was 2.1% (9/427). There were six infections, which required antibiotic therapy and/or IPG removal, in the antibiotic envelope group (6/200) and three in the non-envelope group (3/227) (p = 0.66). Conclusion: This prospective randomised study did not find that an antibiotic envelope reduced the IPG infection rate in our 427 patients undergoing routine DBS IPG replacement. Further research to reduce IPG revisions and infections in a cost-effective manner is required.
Epidemiologic and Clinical Patterns of Malignant Lymphoma in Qatar 2013–2017: A Population-Based Cohort Study
Authors: Adel Ahmad M. , Exarchakou Aimilia , Elshafey Nurhan , Ghazouani Hafedh , Alshurafa Awni , Yassin Mohamed A.
Published: March 2024

Introduction: Lymphoma, encompassing common non-Hodgkin lymphoma (NHL) and less common Hodgkin lymphoma (HL), represents significant hematological malignancies. Advancements in treatment modalities have reshaped survival rates, particularly in NHL. This complexity results in varying outcomes, some requiring extended observation periods and multiple chemotherapy treatments. The primary objective was to explore and compare the overall survival (OS) of HL and NHL at 1, 3, and 5-year follow-ups among adult lymphoma patients in Qatar during January 2013–December 2017. Further objectives encompass comparing the most prevalent histological types, clinical and epidemiological traits of HL and NHL, as well as secondary aims of assessing clinical features, treatment, response, disease-free survival, and OS. Methods: A retrospective, descriptive study of consecutive cases was conducted at Qatar’s NCCCR between 2013 and 2017. Inclusion criteria involved patients ≥18 years old, of any gender and clinical stage at diagnosis, who received chemotherapy and had known outcomes. Descriptive statistics were applied, and survival analysis utilized Kaplan-Meier curves. STATA version 13.0 facilitated data analysis. Results: Between 2013 and 2017, 414 individuals in Qatar were diagnosed with lymphoma. The median age at diagnosis was 49 years (IQR 36–95 years; p < 0.001) across all patients. Males exhibited a higher likelihood of developing HL and NHL, comprising 74% and 70% of cases, respectively, though this difference was statistically insignificant (p = 0.45). Among NHL-B subtypes, mature B-cell neoplasms (60%) predominated, while lymphocyte-rich subtype (49%) was prominent in HL cases. With a median follow-up of 17.3 months, OS rates at 1, 3, and 5 years were 99%, 82%, and 64%, respectively for all lymphoma patients. Subtype stratification revealed trends in 3-year follow-up OS (94 vs. 82%) for HL and NHL, with 5-year OS of 67% and 60%, respectively. HL demonstrated higher OS throughout the study period compared to NHL (p < 0.001), though median OS remained unreached. Conclusions: Diffuse large B-cell lymphoma emerged as the most prevalent subtype among lymphomas in Qatar. Generally, HL exhibited superior survival rates, at 67% compared to 60% for NHL. Minor deflation in survival rates, particularly for HL, might be attributed to Qatar’s immigration patterns.
Spaghetti Connections: Synaptonemal Complexes as a Tool to Explore Chromosome Structure, Evolution, and Meiotic Behavior in Fish
Authors: Lisachov Artem , Dedukh Dmitrij , Simanovsky Sergey , Panthum Thitipong , Singchat Worapong , Srikulnath Kornsorn
Published: March 2024

Background: The synaptonemal complex (SC) is a protein axis formed along chromosomes during meiotic prophase to ensure proper pairing and crossing over. SC analysis has been widely used to study the chromosomes of mammals and less frequently of birds, reptiles, and fish. It is a promising method to investigate the evolution of fish genomes and chromosomes as a part of complex approach. Summary: Compared with conventional metaphase chromosomes, pachytene chromosomes are less condensed and exhibit pairing between homologous chromosomes. These features of SCs facilitate the study of the small chromosomes that are typical in fish. Moreover, it allows the study of heteromorphisms in sex chromosomes and supernumerary chromosomes. In addition, it enables the investigation of the pairing between orthologous chromosomes in hybrids, which is crucial for uncovering the causes of hybrid sterility and asexual reproduction, such as gynogenesis or hybridogenesis. However, the application of SC analysis to fish chromosomes is limited by the associated complications. First, in most fish, meiosis does not occur during every season and life stage. Second, different SC preparation methods are optimal for different fish species. Third, commercial antibodies targeting meiotic proteins have been primarily developed against mammalian antigens, and not all of them are suitable for fish chromosomes. Key Messages: In the present review, we provide an overview of the methods for preparing fish SCs and highlight important studies using SC analysis in fish. This study will be valuable for planning and designing research that applies SC analysis to fish cytogenetics and genomics.
Genetic Testing Yield and Clinical Characteristics of Hypertrophic Cardiomyopathy in Understudied Ethnic Groups: Insights From a New Zealand National Registry
Authors: Earle Nikki J. , Winbo Annika , Crawford Jackie , Wheeler Miriam , Stiles Rachael , Donoghue Tom , Stiles Martin K. , Hayes Ian , Marcondes Luciana , Martin Andrew , Skinner Jonathan R.
Published: March 2024

BACKGROUND:

Aotearoa/New Zealand has a multiethnic population. Patients with hypertrophic cardiomyopathy (HCM) are enrolled in the national Cardiac Inherited Diseases Registry New Zealand. Here, we report the characteristics of Cardiac Inherited Diseases Registry New Zealand HCM probands with and without pathogenic or likely pathogenic (P/LP) genetic variants for HCM, and assess genetic testing yield and variant spectrum by self-identified ethnicity.

METHODS:

Probands with HCM and enrolled in Cardiac Inherited Diseases Registry New Zealand who have undergone clinical genetic testing over a 17-year period were included. Clinical data, family history, and genetic test results were analyzed.

RESULTS:

Of 336 probands, 121 (36%) were women, 220 (66%) were European ethnicity, 41 (12%) were Māori, 26 (8%) were Pacific people, and 49 (15%) were other ethnicities. Thirteen probands (4%) presented with sudden death and 19 (6%) with cardiac arrest. A total of 134 (40%) had a P/LP variant identified; most commonly in the
MYBPC3
gene (60%) followed by the
MYH7
gene (24%). A P/LP variant was identified in 27% of Māori or Pacific probands versus 43% European or other ethnicity probands (
P
=0.022); 16% of Māori or Pacific probands had a variant of uncertain significance identified, compared with 9% of European or other ethnicity probands (
P
=0.092). Women more often had a P/LP variant identified than men (48% versus 35%;
P
=0.032), and variant-positive probands were younger at clinical diagnosis than variant of uncertain significance/variant-negative probands (39±17 versus 50±17 years;
P
<0.001) and more likely to have experienced cardiac arrest or sudden death events over their lifetime (
P
=0.002).

CONCLUSIONS:

Carriage of a P/LP variant in HCM probands is associated with presentation at younger age, and cardiac arrest or sudden death events. Māori or Pacific probands were less likely to have a P/LP variant identified than European or other ethnicity probands.
Rewiring Endothelial Sphingolipid Metabolism to Favor S1P Over Ceramide Protects From Coronary Atherosclerosis
Authors: Manzo Onorina L. , Nour Jasmine , Sasset Linda , Marino Alice , Rubinelli Luisa , Palikhe Sailesh , Smimmo Martina , Hu Yang , Bucci Maria Rosaria , Borczuk Alain , Elemento Olivier , Freed Julie K. , Norata Giuseppe Danilo , Di Lorenzo Annarita
Published: March 2024

BACKGROUND:

Growing evidence correlated changes in bioactive sphingolipids, particularly S1P (sphingosine-1-phosphate) and ceramides, with coronary artery diseases. Furthermore, specific plasma ceramide species can predict major cardiovascular events. Dysfunction of the endothelium lining lesion-prone areas plays a pivotal role in atherosclerosis. Yet, how sphingolipid metabolism and signaling change and contribute to endothelial dysfunction and atherosclerosis remain poorly understood.

METHODS:

We used an established model of coronary atherosclerosis in mice, combined with sphingolipidomics, RNA-sequencing, flow cytometry, and immunostaining to investigate the contribution of sphingolipid metabolism and signaling to endothelial cell (EC) activation and dysfunction.

RESULTS:

We demonstrated that hemodynamic stress induced an early metabolic rewiring towards endothelial sphingolipid de novo biosynthesis, favoring S1P signaling over ceramides as a protective response. This finding is a paradigm shift from the current belief that ceramide accrual contributes to endothelial dysfunction. The enzyme SPT (serine palmitoyltransferase) commences de novo biosynthesis of sphingolipids and is inhibited by NOGO-B (reticulon-4B), an ER membrane protein. Here, we showed that NOGO-B is upregulated by hemodynamic stress in myocardial EC of ApoE
−/−
mice and is expressed in the endothelium lining coronary lesions in mice and humans. We demonstrated that mice lacking NOGO-B specifically in EC (Nogo-A/B
ECKO
ApoE
−/−
) were resistant to coronary atherosclerosis development and progression, and mortality. Fibrous cap thickness was significantly increased in Nogo-A/B
ECKO
ApoE
−/−
mice and correlated with reduced necrotic core and macrophage infiltration. Mechanistically, the deletion of NOGO-B in EC sustained the rewiring of sphingolipid metabolism towards S1P, imparting an atheroprotective endothelial transcriptional signature.

CONCLUSIONS:

These data demonstrated that hemodynamic stress induced a protective rewiring of sphingolipid metabolism, favoring S1P over ceramide. NOGO-B deletion sustained the rewiring of sphingolipid metabolism toward S1P protecting EC from activation under hemodynamic stress and refraining coronary atherosclerosis. These findings also set forth the foundation for sphingolipid-based therapeutics to limit atheroprogression.
Epidermal Growth Factor‐Like Repeats and Discoidin I‐Like Domains 3 Deficiency Attenuates Dilated Cardiomyopathy by Inhibiting Ubiquitin Specific Peptidase 10 Dependent Smad4 Deubiquitination
Authors: Zhao Mengmeng , Zheng Zihui , Peng Shanshan , Xu Yao , Zhang Jishou , Liu Jianfang , Pan Wei , Yin Zheng , Xu Shuwan , Wei Cheng , Wang Menglong , Wan Jun , Qin Juan‐Juan
Published: March 2024

Background

Dilated cardiomyopathy (DCM) is the leading cause of heart failure with a poor prognosis. Recent studies suggest that endothelial to mesenchymal transition (EndMT) may be involved in the pathogenesis and cardiac remodeling during DCM development. EDIL3 (epidermal growth factor‐like repeats and discoidin I‐like domains 3) is an extracellular matrix glycoprotein that has been reported to promote EndMT in various diseases. However, the roles of EDIL3 in DCM still remain unclear.

Methods and Results

A mouse model of DCM and human umbilical vein endothelial cells were used to explore the roles and mechanisms of EDIL3 in DCM. The results indicated that EndMT and EDIL3 were activated in DCM mice. EDIL3 deficiency attenuated cardiac dysfunction and remodeling in DCM mice. EDIL3 knockdown alleviated EndMT by inhibiting USP10 (ubiquitin specific peptidase 10) dependent Smad4 deubiquitination in vivo and in vitro. Recombinant human EDIL3 promoted EndMT via reinforcing deubiquitination of Smad4 in human umbilical vein endothelial cells treated with IL‐1β (interleukin 1β) and TGF‐β (transforming growth factor beta). Inhibiting USP10 abolished EndMT exacerbated by EDIL3. In addition, recombinant EDIL3 also aggravates doxorubicin‐induced EndMT by promoting Smad4 deubiquitination in HUVECs.

Conclusions

Taken together, these results indicate that EDIL3 deficiency attenuated EndMT by inhibiting USP10 dependent Smad4 deubiquitination in DCM mice.
Harnessing RNA Interference for Cholesterol Lowering: The Bench‐to‐Bedside Story of Inclisiran
Authors: Wilkinson Michael J. , Bajaj Archna , Brousseau Margaret E. , Taub Pam R.
Published: March 2024

Lowering low‐density lipoprotein cholesterol (LDL‐C) is a cornerstone of reducing risk for atherosclerotic cardiovascular disease. Despite the approval of nonstatin therapies for LDL‐C lowering over the past 2 decades, these medications are underused, and most patients are still not at guideline‐recommended LDL‐C goals. Barriers include poor adherence, clinical inertia, concern for side effects, cost, and complex prior authorization processes. With atherosclerotic cardiovascular disease‐related mortality increasing globally, there remains a need for additional therapeutic options for lowering LDL‐C as part of an atherosclerotic cardiovascular disease prevention strategy. Following the identification of PCSK9 (proprotein convertase subtilisin/kexin type 9) as a promising therapeutic target, inclisiran was developed using the natural process of RNA interference for robust, sustained prevention of hepatic PCSK9 synthesis. Twice‐yearly maintenance subcutaneous inclisiran (following initial loading doses at Day 1 and Day 90) reduces circulating LDL‐C levels by ≈50% versus placebo when added to maximally tolerated statins. Long‐term safety and tolerability of inclisiran have been assessed, with studies underway to evaluate the effects of inclisiran on cardiovascular outcomes and to provide additional safety and effectiveness data. In 2021, <20 years after the discovery of PCSK9, inclisiran became the first RNA interference therapeutic approved in the United States for LDL‐C lowering in patients with established atherosclerotic cardiovascular disease or familial hypercholesterolemia and has since been approved for use in patients with primary hyperlipidemia. This article reviews the journey of inclisiran from bench to bedside, including early development, the clinical trial program, key characteristics of inclisiran, and practical points for its use in the clinic.
National Trends of Vascular Risk Factor Control Among Stroke Survivors: From the National Health and Nutrition Examination Survey 2009 to 2020
Authors: Mansoor Hend , Manion Daniel , Swafford Kara J. , Jicha Gregory , Moga Daniela
Published: March 2024

Background

Contemporary data describing the national trends on vascular risk factor control among stroke survivors are limited.

Methods and Results

This is a cross‐sectional analysis of the National Health and Nutrition Examination Survey cycles 2009 to 2010 to 2017 to March 2020. Adults (≥18 years of age) with a self‐reported diagnosis of stroke were identified. Age‐adjusted trends in hypertension, diabetes, and hyperlipidemia control were examined. Sex and racial differences in vascular risk factor control were also investigated. Among 32 497 adult individuals who participated in the National Health and Nutrition Examination Survey, 1354 participants (4.2%) self‐reported a prior diagnosis of stroke (55% were women). The rates of age‐adjusted blood pressure control worsened when using the cutoff <140/90 mm Hg (79.1% in 2009–2010 versus 61.5% in 2017–March 2020,
P
trend
<0.001) and using the cutoff <130/80 mm Hg (53.3% in 2009–2010 versus 38.6% in 2017–March 2020,
P
trend
=0.006). Age‐adjusted diabetes control (hemoglobin A1c <7 mg/dL) did not significantly change during the study period (88.8% in 2009–2010 versus 85.9% in 2017–March 2020,
P
trend
=0.41). Achieving a total cholesterol level <200 mg/dL did not change during the study period (67.3% in 2009–2010 versus 73.3% in 2017–March 2020,
P
trend
=0.16). These findings were mostly consistent in men and women and across the different racial and ethnic groups.

Conclusions

In the United States, secondary prevention was suboptimal for stroke survivors, and there has not been any major significant improvement in the rates of achieving the recommended targets for vascular risk factors during the past decade. These findings highlight the need for targeted interventions to improve these modifiable risk factors.
1. An Unthinkable Job for a Woman
Authors: Howsam Leslie
Published: March 2024

This chapter sets the context for Eliza Orme’s ambitions, in England from the 1860s to the 1890s, given that the extraordinary achievement of earning a degree in law was, as it happened, the easy part. She came of age into a burgeoning women’s suffrage movement whose leaders were committed to securing the electoral vote for women as well as access to a wide range of jobs and occupations; they also set their sights on the profession of medicine, but not that of law. The legal professions, encompassing both barristers and solicitors, were so totally closed to women that even the most ambitious suffragist and other feminist politicians did not consider them as institutions open to challenge. This meant that, whatever her contemporaries saw when they looked at Orme, they did not see her as we do today. When Leslie Howsam first encountered Orme in the 1980s, as a postgraduate student of British history in a Canadian university, she could discover very little information about this elusive figure. She had access to libraries and archives at home and in London, but there was no internet searching or digitized newspapers. Almost forty years later, newly available sources have made it possible to speculate that Eliza Orme’s ambition might have transcended even the practice of law, and reached as far as aiming for a seat in Parliament.