bluuebunny/crossref_metadata_2025 huggingface dataset:
Midterm outcomes of transcatheter aortic valve replacement in patients with active cancer
Authors: Noguchi Masahiko , Tabata Minoru , Ito Joji , Kato Nahoko , Obunai Kotaro , Watanabe Hiroyuki , Yashima Fumiaki , Watanabe Yusuke , Naganuma Toru , Yamawaki Masahiro , Yamanaka Futoshi , Shirai Shinichi , Ueno Hiroshi , Tada Norio , Yamamoto Masanori , Hayashida Kentaro
Published: February 2024

Objectives

The clinical outcomes of transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis (AS) and concomitant active cancer remain insufficiently explored. This study aimed to assess the midterm outcomes of TAVR in patients diagnosed with AS and active cancer.

Methods

Data from the OCEAN-TAVI, a prospective Japanese registry of TAVR procedures, was analysed to compare prognoses and clinical outcomes in patients with and without active cancer at the time of TAVR.

Results

Of the 2336 patients who underwent TAVR from October 2013 to July 2017, 89 patients (3.8%) had active cancer, whereas 2247 did not. Among patients with active cancer, 49 had limited-stage cancer (stage 1 or 2). The prevalent cancers identified before TAVR were colon (21%), prostate (18%), lung (15%), liver (11%) and breast (9%). Although the periprocedural complications and 30-day mortality rates were comparable between the groups, the 3-year survival rate after TAVR was notably lower in patients with active cancer (64.7%) than in those without active cancer (74.7%; p=0.016). Nevertheless, the 3-year survival rate of patients with limited-stage cancer (stage 1 or 2) did not significantly differ from those without cancer (70.6% vs 74.7%, p=0.50).

Conclusions

The patients with active cancer exhibited significantly reduced midterm survival rates. However, no distinct disparity existed in those with limited-stage cancer (stage 1 or 2). Although TAVR is a viable treatment in patients with AS with active cancer, the type and stage of cancer and prognosis should be carefully weighed in the decision-making process.
Exogenous hydrogen sulfide prevents SOD2 degradation to safeguard renal function in diabetic kidney disease
Authors: Yang Qian , Wang Mengyi , Wang Huan , Ren Cheng , Li Yifu
Published: February 2024

Diabetic kidney disease (DKD) is a major contributor to chronic kidney disease. Hydrogen sulfide (H2S) serves as an endogenous gaseous signaling molecule capable of safeguarding renal function within the context of DKD. However, the underlying mechanisms need to be elucidated. This study was undertaken to unveil the mechanisms by which H2S counteracts against DKD. Utilizing mice and human renal tubular epithelial (HK-2) cells, we demonstrated a reduction in cystathionine-γ-lyase/H2S levels within renal tissues of db/db mice and in HK-2 cells subjected to hyperglycemic and hyperlipidemic environments. Notably, we observed that sodium hydrosulfide (NaHS) supplementation could serve as an exogenous source of H2S. Exogenous H2S exhibited the capacity to mitigate the accumulation of reactive oxygen species and attenuate the degradation of superoxide dismutase 2 (SOD2) by Lon protease homolog 1 induced by hyperglycemia and hyperlipidemia, thus affording cellular protection against mitochondrial apoptosis. Consequently, NaHS treatment led to decreased serum levels of blood urea nitrogen and serum creatinine, reflecting alleviated renal damage and thereby preserving renal function in db/db mice. Based on these findings, we propose that exogenous H2S exerts a protective role against DKD by inhibiting SOD2 degradation.
QsvR and OpaR coordinately regulate the transcription of cpsS and cpsR in Vibrio parahaemolyticus
Authors: Li Xue , Lian Wei , Zhang Miaomiao , Luo Xi , Zhang Yiquan , Lu Renfei
Published: February 2024

Vibrio parahaemolyticus, the leading cause of seafood-associated gastroenteritis, has a strong capacity to form biofilms on surfaces, which is strictly regulated by the CpsS–CpsR–CpsQ regulatory cascade. OpaR, a master regulator of quorum sensing, is a global regulator that controls multiple cellular pathways including biofilm formation and virulence. QsvR is an AraC-type regulator that works coordinately with OpaR to control biofilm formation and virulence gene expression of V. parahaemolyticus. QsvR and OpaR activate cpsQ transcription. OpaR also activates cpsR transcription, but lacks the detailed regulatory mechanisms. Furthermore, it is still unknown whether QsvR regulates cpsR transcription, as well as whether QsvR and OpaR regulate cpsS transcription. In this study, the results of quantitative real-time PCR and LacZ fusion assays demonstrated that deletion of qsvR and/or opaR significantly decreased the expression levels of cpsS and cpsR compared to the wild-type strain. However, the results of two-plasmid lacZ reporter and electrophoretic mobility-shift assays showed that both QsvR and OpaR were unable to bind the regulatory DNA regions of cpsS and cpsR. Therefore, transcription of cpsS and cpsR was coordinately and indirectly activated by QsvR and OpaR. This work enriched our knowledge on the regulatory network of biofilm formation in V. parahaemolyticus.
Direct drive or slider-crank? Comparing motor-actuated flapping-wing micro aerial vehicles
Authors: Park Moonsoo , Abolfathi Ali
Published: February 2024

For flapping-wing micro aerial vehicles, the common approach to converting the rotational motion of a DC motor to the reciprocal flapping motion is using a slider-crank mechanism. However, frictional losses in sliders and rotational joints can hinder the performance of such a system. An alternative is a direct drive system where the wings are directly connected to a DC motor that has been driven by an AC signal. These two approaches are compared in this paper, to evaluate their performances and assess which one provides a better solution for flapping-wing micro drones. The electromechanical model of the two systems is used in this paper to compare their performances. System parameters for both types of drones were derived through a multi-variable optimisation process using the same DC motor. The comparisons are made in terms of input power requirement, aerodynamic power, system efficiency, and lift. The direct drive model can generate about 16% higher average lift at 5 V with 50% lower input electrical power. It has 29% larger aerodynamic power and the system efficiency is 16.0% higher than that of the slider-crank model.
Recent advances in screening and identification of PET-degrading enzymes
Authors: Sun Shengwei
Published: February 2024

Polyethylene terephthalate (PET) is widely used in plastic bottles, packaging, and textile fibers. However, PET is difficult to degrade in nature and rapidly accumulates into the environment, causing serious environmental pollution and threatening human health. At present, the recycling methods for PET mainly focus on physical recycling and chemical degradation, but these methods have severe limitations, resulting in the great loss of valuable materials and secondary pollution. In contrast, the biodegradation of PET is gradually attracting attention because of its environmental friendliness, high efficiency, and cost-effectiveness. Several PET-degrading enzymes (PDEs) have been previously identified, such as cutinase, IsPETase, lipase, and esterase. Thereafter, many efforts have been made to push the boundaries of evolution schemes, attempting to create stronger PDEs with improved activity and stability. Nevertheless, most of these enzymes show preferences toward low-crystallinity (<10%) PET, while in situ enzymatic degradation of high-crystallinity PET (30%–50%) remains a major challenge. Exploring and engineering PDEs that can efficiently degrade bottle-grade PET plastics has recently become a research hotspot. This review systematically introduces the current advances in PDEs and emphasizes the role of metagenomics in screening and identifying new PDEs.
Circular orbits and collisions of particles with magnetic dipole moment near magnetized Kerr black holes in modified gravity
Authors: Khan Saeed Ullah , Uktamov Uktamjon , Rayimbaev Javlon , Abdujabbarov Ahmadjon , Ibragimov Inomjon , Chen Zhi-Min
Published: February 2024

Throughout this work, we explored the dynamics of test particles with magnetic dipole moment around magnetized rotating Kerr black holes in scalar–vector–tensor gravity theory (STVG), known as modified gravity theory (MOG). We assume that the black hole is immersed in external asymptotically uniform magnetic fields. We derive effective potential for circular orbits of the magnetized particles, taking into account both the magnetic and STVG interactions. We study profiles of the position of the innermost stable circular orbits (ISCOs) of the magnetized particles. We show that the MOG interaction is essentially, and the magnetic interaction enhances its effects on the ISCO radius and the angular momentum at ISCO. Also, we consider collisional cases of magnetized particles and the maximum and minimum limits of angular momentum that ensure the particle colliding near the horizon. Finally, we analyze the center-of-mass energy of colliding magnetized particles near the black hole horizon.
Higher-order structures of local collaboration networks are associated with individual scientific productivity
Authors: Yang Wenlong , Wang Yang
Published: February 2024

The prevalence of teamwork in contemporary science has raised new questions about collaboration networks and the potential impact on research outcomes. Previous studies primarily focused on pairwise interactions between scientists when constructing collaboration networks, potentially overlooking group interactions among scientists. In this study, we introduce a higher-order network representation using algebraic topology to capture multi-agent interactions, i.e., simplicial complexes. Our main objective is to investigate the influence of higher-order structures in local collaboration networks on the productivity of the focal scientist. Leveraging a dataset comprising more than 3.7 million scientists from the Microsoft Academic Graph, we uncover several intriguing findings. Firstly, we observe an inverted U-shaped relationship between the number of disconnected components in the local collaboration network and scientific productivity. Secondly, there is a positive association between the presence of higher-order loops and individual scientific productivity, indicating the intriguing role of higher-order structures in advancing science. Thirdly, these effects hold across various scientific domains and scientists with different impacts, suggesting strong generalizability of our findings. The findings highlight the role of higher-order loops in shaping the development of individual scientists, thus may have implications for nurturing scientific talent and promoting innovative breakthroughs.
Two-parameter deformed quantum mechanics based on Fibonacci calculus and Debye crystal model of two-parameter deformed quantum statistics
Authors: Algin Abdullah , Chung Won Sang
Published: February 2024

Starting on the basis of Fibonacci calculus and Fibonacci oscillator algebra, we introduce the main properties to develop a new formalism for the two-parameter $$({q}_{1},{q}_{2})$$

(

q
1

,

q
2

)

-deformed quantum mechanics, where $${q}_{1}$$

q
1

and $${q}_{2}$$

q
2

are real positive independent deformation parameters. As applications of such a two-parameter deformed formalism, we investigate the behavior of a quantum particle in some different physical phenomena covering the free particle and the inverse-harmonic potential case. The effect of two deformation parameters on the wave functions for these applications is studied. Another application is carried out onto the quantum statistics of lattice oscillations through a model of the $$({q}_{1},{q}_{2})$$

(

q
1

,

q
2

)

-deformed phonon gas, and it is shown that the high- and low-temperature behavior of the model specific heat differs notably from the classical theories for the interval $$0<({q}_{1},{q}_{2})<\infty $$

0
<
(

q
1

,

q
2

)
<
∞

. We also construct a two-parameter deformed non-extensive entropy based on some elements of the Fibonacci calculus and discuss its possible connection with the Tsallis entropy in non-extensive statistical mechanics. Finally, other possible application areas of the present two-parameter $$({q}_{1},{q}_{2})$$

(

q
1

,

q
2

)

-deformed construction on quantum mechanics are discussed.
Improved thermoelectric performance of Bi2Te2.7Se0.3 with honey dispersion
Authors: He Qinglin , Yang Delin , Zhang Wanwan , Song Hongzhang
Published: February 2024

Bi2Te3-based alloys are only commercial thermoelectric materials. While, currently, n-type Bi2Te[Formula: see text]Se[Formula: see text]-based alloys commonly have lower ZT values than those of p-type Bi[Formula: see text]Sb[Formula: see text]Te3 based alloys. In this paper, the influence of different amounts of dispersing honey on the thermoelectric performance of n-type Bi2Te[Formula: see text]Se[Formula: see text] alloys synthesized by the hydrothermal and hot-pressing methods was investigated. The carbon atoms contained in honey could increase lattice defects and grain boundary density effectively, and improved the Seebeck coefficient and suppress lattice thermal conductivity simultaneously. By adjusting the amount of honey, the maximum ZT value reached 0.82 at 423[Formula: see text]K, which was approximately 65% higher than that of the pristine Bi2Te2.7Se0.3.
Illustration of thermal buoyancy on the flow of MHD Casson CNT–water nanofluids over a vertical stretching surface
Authors: Sethy Nilanchala , Mishra S. R.
Published: February 2024

This study addresses the applications of non-uniform heat source/sink and viscous dissipation in the magnetohydrodynamic (MHD) flow of Casson nanoparticles toward a porous stretchable sheet. The free convective flow for the inclusion of thermal buoyancy along with dissipative heat encourages the flow phenomena. The governing equations of the flow model are presented in terms of partial differential equations and then transformed into a system of ordinary differential equations using similarity transformations. These systems of equations are solved numerically by using the Runge–Kutta fourth-order method with a very efficient shooting technique. The effects of various parameters such as the Casson parameter, elastic parameter, porosity parameter, Prandtl number, non-uniform heat source/sink constant, Eckert number, skin fraction and Nusselt number on the flow area are computed and represented graphically. The present results reflect that the velocity of nanoparticles declined effectively with the porosity parameter and nanoparticle volume fraction. The temperature profile is increased with the elastic parameter and heat source parameter while decreasing with the Eckert number and Casson fluid parameter. Moreover, it is observed that when the Hartmann number is maximum, a retardation in wall shear force against nanoparticles volume fraction is marked.
Effect of heat treatments on mechanical properties and wear resistance of laser-powder bed-fused Ti6Al4V alloy
Authors: Wang Sen , Wang Linzhi , Li Jing , Li Ting , Qiu Yingkun , Yang Runqi
Published: February 2024

The effects of heat treatment on the microstructure, mechanical properties and wear resistance of Selective Laser Melting Ti6Al4V alloy were systematically studied. The results show that the as-built part has an acicular [Formula: see text] martensite structure. The increase in heat treatment temperature causes the decomposition of acicular [Formula: see text] martensite, which leads to the decrease of the hardness of Ti6Al4V alloy. When the heat treatment temperature is 800∘C, the alloy forms an [Formula: see text]/[Formula: see text] structure, which increases the tensile strength and elongation of the alloy by 12% and 23%, respectively. When the heat treatment reaches above 900∘C, the mechanical properties of the alloy decrease sharply due to the disappearance of the [Formula: see text]/[Formula: see text] structure, the coarse grains of the [Formula: see text] phase, and the increase of the content of the [Formula: see text] phase. The tensile strength decreased from 935[Formula: see text]MPa to 815[Formula: see text]MPa, and the elongation decreased from 8.7% to 3.1%. With the increase of heat treatment temperature, the friction coefficient and wear rate increase linearly, which is opposite to the changing trend of hardness, and the wear mechanism is changed from single abrasive wear to abrasive wear and oxidative wear. This is attributed to the increase in the grain size of the alloy and the increase in the content of the [Formula: see text] phase, resulting in a decrease in the overall hardness of the alloy.
The algebra Uq+ and its alternating central extension 𝒰q+
Authors: Terwilliger Paul
Published: February 2024

Let [Formula: see text] denote the positive part of the quantized enveloping algebra [Formula: see text]. The algebra [Formula: see text] has a presentation involving two generators [Formula: see text], [Formula: see text] and two relations, called the [Formula: see text]-Serre relations. In 1993 Damiani obtained a PBW basis for [Formula: see text], consisting of some elements [Formula: see text], [Formula: see text], [Formula: see text]. In 2019, we introduced the alternating central extension [Formula: see text] of [Formula: see text]. We defined [Formula: see text] by generators and relations. The generators, said to be alternating, are denoted [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]. Let [Formula: see text] denote the subalgebra of [Formula: see text] generated by [Formula: see text], [Formula: see text]. It is known that there exists an algebra isomorphism [Formula: see text] that sends [Formula: see text] and [Formula: see text]. Via this isomorphism we identify [Formula: see text] with [Formula: see text]. In our main result, we express the Damiani PBW basis elements in terms of the alternating generators. We give the answer in terms of generating functions. A key step is a factorization of the generating function for the elements that generate the center of [Formula: see text].
Graver bases of shifted numerical semigroups with 3 generators
Authors: Howard James , O’Neill Christopher
Published: February 2024

A numerical semigroup [Formula: see text] is a subset of the non-negative integers that is closed under addition. A factorization of [Formula: see text] is an expression of [Formula: see text] as a sum of generators of [Formula: see text], and the Graver basis of [Formula: see text] is a collection [Formula: see text] of trades between the generators of [Formula: see text] that allows for efficient movement between factorizations. Given positive integers [Formula: see text], consider the family [Formula: see text] of “shifted” numerical semigroups whose generators are obtained by translating [Formula: see text] by an integer parameter [Formula: see text]. In this paper, we characterize the Graver basis [Formula: see text] of [Formula: see text] for sufficiently large [Formula: see text] in the case [Formula: see text], in the form of a recursive construction of [Formula: see text] from that of smaller values of [Formula: see text]. As a consequence of our result, the number of trades in [Formula: see text], when viewed as a function of [Formula: see text], is eventually quasilinear. We also obtain a sharp lower bound on the start of quasilinear behavior.
Nexus Between Strategic Green Finance and Green Competitive Advantage: Study at Indonesia Corporate
Authors: Nohong Mursalim , Sobarsyah Muhammad , Sohilauw Muhammad Irfai , Herman Bahtiar
Published: February 2024

The present research explores the variables that impact Green Competitive Advantage (GCA) in modern business environments. It highlights the importance of strategic investments in green finance and the strong association between Strategic Finance (SFI) and GCA, which aligns with the growing emphasis on sustainable business practices worldwide. Furthermore, the study reveals the correlation between Corporate Governance (CG), business Size (CS), and GDP, emphasizing the critical function of solid governance frameworks and the utilization of business scale to align with broader economic trends. However, discovering multicollinearity among particular variables underscores the necessity for caution when interpreting regression model results. In addition, incorporating a geographical dimension yields refined insights that disclose characteristics distinctive to a specific place and globally relevant determinants that affect GCA. Ultimately, companies that want to be sustainable and competitive must take a holistic approach considering governance, strategic finance, and location.
Futures Replication and the Law of One Futures Price
Authors: Bick Avi
Published: February 2024

We define a synthetic futures contract as a pair consisting of a terminal futures price [Formula: see text] (a prespecified random variable) and a zero-value trading strategy whose terminal cumulative cash flow is equal to [Formula: see text] to within an additive constant. The construction of synthetic futures contracts is demonstrated for (i) futures on futures, (ii) futures on spot, (iii) quanto futures on futures, (iv) quanto futures on spot and (v) futures on foreign futures and domestic futures. We formulate and derive the Law of One Futures Price, which justifies futures pricing based on such replication.
An Input–Output Feedback Linearization-Based Exponentially Stable Controller for Multi-UAV Payload Transport
Authors: Rao Nishanth , Sundaram Suresh
Published: February 2024

In this paper, an exponentially stable trajectory tracking controller is proposed for multi-UAV payload transport. The multi-UAV payload system has a 2-DOF magnetic spherical joint between the UAVs and the vertical rigid links of the payload frame so that the UAVs can roll or pitch freely. These vertical links are rigidly attached to the payload and cannot move. An input–output feedback linearized model is derived for the complete payload-UAV system along with thrust vectoring control for trajectory tracking of the payload. Theoretical analysis of tracking control laws is shown to be exponentially stable, thus guaranteeing safe transportation along the desired trajectory. To validate the performance of the proposed control law, the results for a numerical simulation as well as a high-fidelity Gazebo real-time simulation are presented. The tracking performance is compared to the existing techniques in the literature, and it is seen that the proposed approach has the least RMSE for tracking performance. Next, the robustness of the proposed controller is analyzed against two practical situations: External disturbance on the payload and payload mass uncertainty. The results clearly indicate that the proposed controller is robust and computationally efficient while achieving exponentially stable trajectory tracking.
From Pixels to Play: Opportunities and Challenges of a Diverse and Democratized Games Industry
Authors: Long Sebastian , Denisova Alena , Mirza-Babaei Pejman
Published: February 2024

This forum features game-practitioner perspectives on the interaction design process, techniques, and evaluation involved in creating playful experiences. We focus on how technology advancement, infrastructure, and constraints shape the player experience.
Low-Overhead Trace Collection and Profiling on GPU Compute Kernels
Authors: Darche Sébastien , Dagenais Michel R.
Published: February 2024

While GPUs can bring substantial speedup to compute-intensive tasks, their programming is notoriously hard. From their programming model, to microarchitectural particularities, the programmer may encounter many pitfalls which may hinder performance in obscure ways. Numerous performance analysis tools provide helpful data on the efficiency of the compute kernels, but few allow the programmer to efficiently gather runtime information directly on the device and pinpoint the sections to optimize.

We propose in this article an instrumentation method to collect traces while executing the compute kernel, with a reduced overhead compared with other approaches, by exploiting the inherently parallel behavior of GPUs and compartmentalizing tracing phases. The reference implementation is freely available and induces an average overhead of 1.6 × on a popular scientific computing benchmark and 1.5 × over the kernel execution time. This represents an improvement of an order of magnitude compared with similar work, and proves useful for timing-guided optimizations. The tool generates insightful execution traces and timestamps which can be analyzed to better understand performance issues in the kernel.
Enhancing Red Brick Performance: A Study on Aluminum Oxide/Graphite Composite Material Effects
Authors: S. Chetana , V. Shravan , Rani Navya , Verma Ashutosh , G. K. Puneetha , Rangappa Dinesh
Published: February 2024

The objective of this research was to add nano/micro composites to red bricks in order to reduce costs while increasing strength. A finite element model (FEM COMSOL) was created to determine the best cavity design and placement in nano/micro composite bricks in order to decrease density and boost mechanical characteristics. Several nano/micro composite materials were used to broaden this red brick’s mechanical, electrical, energy storage, and thermal uses. The development of a finite element model COMSOL for red brick blocks with the ideal cavity shape and location for analyzing mechanical characteristics was applied for the first time in the paper. The concrete blocks were produced and strengthened using two distinct types of nano/micro materials to further enhance the stretcher of red bricks’ nanocomposites. The addition of Al2O3/Graphite NPs influences the mechanical properties of clay bricks. A detached study of Al2O3/Graphite nanoparticles affects the mechanical properties of clay bricks including compressive strength, water absorption, and density is reported. It also includes the comparison of traditional clay bricks with Al2O3/Graphite NPs mixtures.
Argon Nanocluster Filled Between Twisted Bilayer Graphene: Molecular Dynamics Simulation
Authors: Cui Shuwen , Wu Yulin , Hui Shuangshuang , Li Qiang , Liu Weiwei
Published: February 2024

In 2004, graphene was discovered by Novoselov and Geim. With the development of technology，twisted bilayer graphene (tBLG) has become a hot research topic. On the basis of predecessors, we further study the confined spaces between twisted bilayer graphene. The interlayer spacing between them is expected to modify properties of atoms and molecules confined at the atomic interfaces. The effects of twist angle, interlayer spacing of the tBLG and temperature (20 K–70 K) on the equilibrium structure of argon cluster are systematically studied by means of molecular dynamics simulation with the tBLG being considered to be fixed. As the interlayer spacings of tBLGs with different twist angles increase at a fixed temperature 20 K, the equilibrium structures of the argon cluster transform from a monoatomic layer to multilayer structure. For different twist angles at the fixed interlayer spacing, the structures of the argon cluster gradually form periodic pattern (similar to moiré pattern). The effects of temperature and non-equiliblium suddenly heating process on the structures of argon clusters between tBLGs are also studied by molecular dynamics simulation. Our results may provide a theoretical support for the preparation of new carbon-based intercalated composites and the application of graphene.
Influence of the Synthesis Process on the Physical Property Characteristics of BiFeO3 Ceramics Prepared by Flux-based Molten Salt and Solid-state Reaction Route: A Comparative Study
Authors: Mitra Priyanka , Jahangeer N. , Venkataraman B. Harihara
Published: February 2024

This work reports the influence of the solid-state reaction (SSR) and molten-salt synthesis (MSS) routes on the physical properties of the multiferroic BiFeO3 (BFO) compound exploited for capacitors and memory devices. Rietveld refinement reveals that the MSS-derived BFO ceramics have exhibited a pure-phase distorted rhombohedral perovskite structure at low temperatures (650 °C) compared to the SSR method. The FE-SEM illustrates the uniform distribution of spherical-shaped BFO grains. By altering the fabrication route, the calculated bandgap values of BFO were tuned within the range of (2.14 ± 0.02) to (2.05 ± 0.02) eV based on Tauc’s plot. The suppression of oxygen vacancies led to better dielectric characteristics at higher frequencies in the MSS-prepared BFO nanoceramics. Also, the MSS-derived BFO ceramics possessed a typical canted-AFM loop with a higher MR value of ∼2.73×10−2 emu g−1. These observations suggest that fabrication techniques have a decisive effect on the phase formation kinetics and multiferroic properties of BFO ceramics.
Identifying G6PC3 as a Potential Key Molecule in Hypoxic Glucose Metabolism of Glioblastoma Derived from the Depiction of 18F-Fluoromisonidazole and 18F-Fluorodeoxyglucose Positron Emission Tomography
Authors: Okamoto Michinari , Yamaguchi Shigeru , Sawaya Ryosuke , Echizenya Sumire , Ishi Yukitomo , Kaneko Sadahiro , Motegi Hiroaki , Toyonaga Takuya , Hirata Kenji , Fujimura Miki
Published: February 2024

Purpose. Glioblastoma is the most aggressive primary brain tumor, characterized by its distinctive intratumoral hypoxia. Sequential preoperative examinations using fluorine-18-fluoromisonidazole (18F-FMISO) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) could depict the degree of glucose metabolism with hypoxic condition. However, molecular mechanism of glucose metabolism under hypoxia in glioblastoma has been unclear. The aim of this study was to identify the key molecules of hypoxic glucose metabolism. Methods. Using surgically obtained specimens, gene expressions associated with glucose metabolism were analyzed in patients with glioblastoma (n=33) who underwent preoperative 18F-FMISO and 18F-FDG PET to identify affected molecules according to hypoxic condition. Tumor in vivo metabolic activities were semiquantitatively evaluated by lesion-normal tissue ratio (LNR). Protein expression was confirmed by immunofluorescence staining. To evaluate prognostic value, relationship between gene expression and overall survival was explored in another independent nonoverlapping clinical cohort (n=17) and validated by The Cancer Genome Atlas (TCGA) database (n=167). Results. Among the genes involving glucose metabolic pathway, mRNA expression of glucose-6-phosphatase 3 (G6PC3) correlated with 18F-FDG LNR (P=0.03). In addition, G6PC3 mRNA expression in 18F-FMISO high-accumulated glioblastomas was significantly higher than that in 18F-FMISO low-accumulated glioblastomas (P<0.01). Protein expression of G6PC3 was consistent with mRNA expression, which was confirmed by immunofluorescence analysis. These findings indicated that the G6PC3 expression might be facilitated by hypoxic condition in glioblastomas. Next, we investigated the clinical relevance of G6PC3 in terms of prognosis. Among the glioblastoma patients who received gross total resection, mRNA expressions of G6PC3 in the patients with poor prognosis (less than 1-year survival) were significantly higher than that in the patients who survive more than 3 years. Moreover, high mRNA expression of G6PC3 was associated with poor overall survival in glioblastoma, as validated by TCGA database. Conclusion. G6PC3 was affluently expressed in glioblastoma tissues with coincidentally high 18F-FDG and 18F-FMISO accumulation. Further, it might work as a prognostic biomarker of glioblastoma. Therefore, G6PC3 is a potential key molecule of glucose metabolism under hypoxia in glioblastoma.
Major Limitations of Cardiovascular Risk Scores
Authors: Talha Ibtissam , Elkhoudri Noureddine , Hilali Abderraouf
Published: February 2024

Background. Epidemiological studies conducted in extensive population cohorts have led to the creation of numerous cardiovascular risk predictor models. However, these tools have certain limitations that restrict its applicability. The aim behind the following work is to summarize today’s best‐known limitations of cardiovascular risk assessment models through presenting the critical analyses conducted in this area, with the intention of offering practitioners a comprehensive understanding of these restrictions. Critical analyses revealed that these scales exhibit numerous limitations that could impact their performance. Most of these models evaluate cardiovascular risk based on classic risk factors and other restrictions, thereby negatively affecting their sensitivity. Scientists have made significant advancements in improving cardiovascular risk models, tailoring them to accommodate a wide range of populations and devising scales for estimating cardiovascular risks that can account for all prevailing restrictions. Better understanding these limitations could improve the cardiovascular risk stratification.
Deep-Learning Model for Tumor-Type Prediction Using Targeted Clinical Genomic Sequencing Data
Authors: Darmofal Madison , Suman Shalabh , Atwal Gurnit , Toomey Michael , Chen Jie-Fu , Chang Jason C. , Vakiani Efsevia , Varghese Anna M. , Balakrishnan Rema Anoop , Syed Aijazuddin , Schultz Nikolaus , Berger Michael F. , Morris Quaid
Published: February 2024

Tumor type guides clinical treatment decisions in cancer, but histology-based diagnosis remains challenging. Genomic alterations are highly diagnostic of tumor type, and tumor-type classifiers trained on genomic features have been explored, but the most accurate methods are not clinically feasible, relying on features derived from whole-genome sequencing (WGS), or predicting across limited cancer types. We use genomic features from a data set of 39,787 solid tumors sequenced using a clinically targeted cancer gene panel to develop Genome-Derived-Diagnosis Ensemble (GDD-ENS): a hyperparameter ensemble for classifying tumor type using deep neural networks. GDD-ENS achieves 93% accuracy for high-confidence predictions across 38 cancer types, rivaling the performance of WGS-based methods. GDD-ENS can also guide diagnoses of rare type and cancers of unknown primary and incorporate patient-specific clinical information for improved predictions. Overall, integrating GDD-ENS into prospective clinical sequencing workflows could provide clinically relevant tumor-type predictions to guide treatment decisions in real time.

Significance:

We describe a highly accurate tumor-type prediction model, designed specifically for clinical implementation. Our model relies only on widely used cancer gene panel sequencing data, predicts across 38 distinct cancer types, and supports integration of patient-specific nongenomic information for enhanced decision support in challenging diagnostic situations.

See related commentary by Garg, p. 906.

This article is featured in Selected Articles from This Issue, p. 897
Secondhand Smoke Exposure and Risk of Dementia in Nonsmokers: A Population-Based Cohort Study
Authors: Wan Zhongxiao , Zhang Xiaohui , He Huanying , Zhang Yebing , Chen Guo-Chong , Qin Li-Qiang , Zhang Na , Li Fu-Rong
Published: February 2024

Background: Large population-based prospective studies are necessary to provide clarification on the associations of panoramic secondhand smoking burden, including prenatal and postnatal secondhand smoke (SHS) exposure, with the risk of developing dementia. Methods: Our study comprised a sample of 353,756 dementia-free individuals from the UK Biobank who were nonsmokers had data on the exposure of maternal smoking as well as SHS exposure in daily life, which was quantified in terms of hours per week (h/week) and whether they lived with household smokers. Multivariable Cox regression models were utilized to analyze the independent and joint associations of maternal smoking and daily life SHS exposure with dementia risk. Results: During a median follow-up of 11.8 years, 4,113 participants developed dementia. Compared with those who lived in the environment without smokers, multivariable-adjusted hazard ratios (HRs) (95% CIs) were 1.11 (1.02, 1.20) and 1.31 (1.13, 1.52) for those who exposed to SHS for >0 but ≤4 h/week and >4 h/week, respectively, and was 1.25 (1.13, 1.39) for those who lived with smokers in the household. A positive history of maternal smoking was associated with a modestly higher risk of dementia (HR = 1.07; 95% CI: 1.01, 1.15). Furthermore, compared with participants with neither history of maternal smoking nor exposure to SHS, a particularly higher risk of dementia was observed among those with both exposures (HR = 1.48; 95% CI: 1.18, 1.86). Additionally, the HR (95% CI) was 1.32 (1.10, 1.59) when comparing participants with a history of maternal smoking who lived with smokers in their households with those who had neither exposures. Conclusions: Having a history of maternal smoking, longer exposure to SHS, and living with smokers in the household were each associated with an increased risk of developing dementia. Individuals who were simultaneously exposed to maternal smoking and SHS or lived with household smokers had a particularly higher dementia risk.
Decrease in Mycophenolic Acid Plasma Level by Sacubitril/Valsartan in a Lupus Nephritis Patient: A Case Report
Authors: Nashimoto Shunsuke , Miyamae Masashi , Higuchi Issei , Kono Michihito , Tada Maria , Atsumi Tatsuya , Sugawara Mitsuru , Takekuma Yoh
Published: February 2024

Introduction: Mycophenolate mofetil (MMF), an inactive prodrug of mycophenolic acid (MPA), is an immunosuppressive drug used widely in the treatment of lupus nephritis. In this case report, the area under the blood concentration time curve (AUC) of MPA was significantly decreased by the concomitant use of sacubitril/valsartan. Case Presentation: The patient was a man in his 40s with a diagnosis of lupus nephritis class IVa/c+V. MMF dose was 1.5 g/day at admission, and AUC of MPA on day 14 was 25.1 μg⋅h/mL. Owing to poor blood pressure control, sacubitril/valsartan was initiated at 97/103 mg/day on day 29. On day 37, AUC of MPA was significantly decreased to 8.7 μg⋅h/mL, suggesting drug interaction with the newly initiated sacubitril/valsartan. Sacubitril/valsartan was decreased to 49/51 mg/day, and AUC of MPA on day 67 was 37.6 μg⋅h/mL, achieving the target range. The final MMF dose was set at 1.75 g/day. A possible mechanism of drug interaction between sacubitril/valsartan and MPA involves an organic anion transporting polypeptide (OATP). The inhibition of OATPs by sacubitril may have interrupted the enterohepatic circulation of MPA, resulting in a lower plasma concentration. Conclusion: Since lupus nephritis is often associated with hypertension, the drug interaction observed in this report may also occur in other cases. However, it is impossible to conclude that the decrease in plasma MPA levels was due to the concomitant use of sacubitril/valsartan, and more cases and basic findings are needed.
Positive Long-Term Outcome of Kidney Allocation via Acceptable Mismatch Program in Highly Sensitized Patients
Authors: Strehler Yara , Lachmann Nils , Niemann Matthias , Halleck Fabian , Budde Klemens , Pruß Axel
Published: February 2024

Introduction: Eurotransplant established the acceptable mismatch (AM) program to facilitate timely kidney transplantations of highly sensitized patients, but long-term granular clinical and immunological outcomes regarding overall graft survival and de novo DSA (dnDSA) formation are still intensively researched. The right choice of induction therapy in patients with differing immunological risk is not conclusively determined, as well as the impact of human leukocyte antigen (HLA) epitope matching on dnDSA formation. Methods: This monocentric, retrospective study analyzed 94 patients transplanted within the AM program between 2000 and 2019 compared to case-control matched cohorts of non- (PRA 0–5%; PRA-0) and intermediately sensitized (PRA 6–84%; PRA-6/84) patients transplanted through Eurotransplant Kidney Allocation System. Results: Estimated 10-year overall graft survival between the PRA-0 and AM cohorts was similar, whereas PRA-6/84 was significantly disadvantageous compared to PRA-0. Estimated 10-year incidence of antibody-mediated rejection rates was significantly lower in the PRA-0 group compared to AM and PRA-6/84 groups. Compared to the AM group, estimated incidence of de novo donor-specific antibody (dnDSA) was significantly lower in PRA-0 patients, with no differences between the AM and PRA-6/84 cohorts. The PRA-6/84 cohort was the only subgroup in which interleukin-2 receptor antagonist (IL2RA) induction was associated with longer overall graft survival, patient survival, and graft survival compared to depleting induction (ATG or OKT3). Broad HLA-A, -B, -DR mismatches (mmABDR) and HLA epitope mismatches determined by Eplets and PIRCHE-II were predictive for dnDSA formation in the total cohort, and the AM subgroup. Discussion: The high efforts expended on AM patients are justified to allow timely organ transplantation with acceptable risk profile and non-inferior outcomes. IL2RA induction in intermediately sensitized patients is associated with superior overall graft survival, patient survival, and graft survival compared to ATG/OKT3 induction, without negative effects on rejection episodes or dnDSA formation. In silico epitope matching might further help reduce dnDSA formation, particularly in high-risk AM patients.
Associations of Depressive and Anxiety Disorders with Pulmonary Disorders in the Community: The PneumoLaus and PsyCoLaus Studies
Authors: Touilloux Brice , Casutt Alessio , Strippoli Marie-Pierre F. , Lenoir Alexandra , Janett Simone , Vollenweider Peter , Vaucher Julien , Nicod Laurent , Preisig Martin , Von Garnier Christophe
Published: February 2024

Introduction: Mental health disorders figure among the many comorbidities of obstructive respiratory diseases. The multisystemic characteristics of chronic respiratory disease and its impact on quality of life could affect depressive and/or anxiety disorders. We aimed to evaluate the association of spirometric indices, ventilatory disorders, and self-reported respiratory diseases with psychiatric disorders considering potential confounders. Methods: We analysed data from CoLaus|PsyCoLaus, a Swiss population-based cohort study, consisting of 2’774 participants (56% women; mean age: 62.3 (standard deviation = ±9.9) years) who performed spirometry and completed semi-structured psychiatric interviews. We defined ventilatory disorders using GLI-2012 references. Major depressive episode (MDE) and anxiety disorders were defined using the DSM-IV (Diagnostic and Statistical Manual). Results: 630 subjects (22.7%) presented a recent MDE. Reversible obstructive ventilatory disorders were associated with recent MDE (OR = 1.94, 95% confidence interval (95% CI) 1.10–3.43) and recent anxiety disorders (2.21 [1.16–4.22]) only in unadjusted model. Self-reported chronic obstructive pulmonary (COPD) and asthma were associated with MDE with ORs of 2.49 (95% CI, 1.19–5.27) and 1.56 (95% CI, 1.04–2.35) after adjustment, respectively. Possible restrictive ventilatory impairment was positively associated with recent anxiety disorders (OR = 2.46, 1.10–5.51). Z-scores of FEV1, FVC, and maximal mid-expiratory flow were not associated with psychiatric disorders. There was no association between ventilatory disorders and MDE in adjusted models. Conclusions: In this cross-sectional population-based study, the association between respiratory disorders and depressive disorders was observed for self-reported COPD and asthma, but not with objective diagnoses based on spirometry. Lung volumes are not associated with psychiatric disorders. Further prospective studies will be necessary to understand the significance of the association.
The impact of COVID-19 on resident doctors as the frontline in health services
Authors: Maghfirah Desi , Yusuf Muhammad , Pamungkas Subhan Rio , Firdausa Sarah , Eljatin Muhammad Ridho Akbar , Febriyanti Sherina Arfi
Published: February 2024

As the number of confirmed cases of COVID-19 increases, the workload due to the pandemic can affect health workers and increase the risk of psychological stress. Psychological factors such as anxiety can cause various physiological responses, including gastroesophageal reflux disease (GERD) symptoms. The persistent symptoms of GERD can reduce the patient's quality of life. A cross-sectional survey was conducted in October 2021 at the Dr. Zainoel Abidin Regional General Hospital, Banda Aceh. A total of 91 Specialist Medical Education Program responded to the study. Data from respondents were collected through the generalized anxiety disorder-7 (GAD-7), GERD-Q, and WHOQOL-BREF questionnaires. The statistical analysis used was the contingency coefficient test. The results showed that 9.9% of respondents experienced suggestive GERD, minimal anxiety (92%), and good quality of life (51.6%). There was a significant relationship between anxiety levels and quality of life and the GERD prevalence of Specialist Doctor Education Program Participants during the COVID-19 pandemic (p<0.05). Most Specialist Medical Education Program participants did not suffer from GERD with minimal anxiety, followed by mild and moderate anxiety. The majority had a good and moderate quality of life during the COVID-19 pandemic.
Minerals and dietary fibre source snack made from Moringa leaves enriched with ginger
Authors: Kustiani Ai , Adyas Atikah , Nurdin Samsu Udayana , Indriani Yaktiworo
Published: February 2024

The findings from the 2021 Indonesian Nutritional Status Study reveal a substantial 24.4% prevalence of child stunting, emphasizing the need for diverse strategies to achieve the desired target. One such strategy involves ensuring the nutritional well-being of expectant mothers to prevent stunting. Moringa leaves are a rich source of essential nutrients. Incorporating Moringa leaf powder into catfish flour-based snacks can boost their protein and mineral content while overcoming any undesirable odors, though this application is currently limited to crackers. This study aimed to create snack products using Moringa leaves, such as tea, brownies, and pudding, with the addition of ginger to enhance dietary fiber and mineral content for pregnant women. The top formulations identified through sensory assessment are F1 tea, F1 brownies, and F2 pudding. These specific tea, brownies, and pudding variations boast dietary fiber content exceeding 3 grams and meet or exceed 15% of the recommended daily intake levels for iron and zinc for pregnant women, as stipulated by the nutrition label reference. As a result, they can be classified as wholesome snacks rich in dietary fiber, iron, and zinc.
Family support, need for achievement, and entrepreneurial orientation on entrepreneurial intentions in vulnerable groups
Authors: Tentama Fatwa , Mulasari Surahma Asti , Sukesi Tri Wahyuni , Sulistyawati Sulistyawati , Subardjo Subardjo
Published: February 2024

This study aims to design and test the goodness of fit of a theoretical model that describes the effect of family support, need for achievement, and entrepreneurial orientation on entrepreneurial intentions with empirical data in the field. Research participation used subjects totaling 66 people from Ngalang village who were female, did not have permanent jobs, and were included in the poor category. Data collection uses four measurement scales: the entrepreneurial intention scale, family support scale, need for achievement scale, and entrepreneurial orientation scale, and is analyzed using partial least square (PLS) via smartPLS 3.0. The results of the study show the formation of a theoretical model of the influence of family support, need for achievement, and entrepreneurial orientation on entrepreneurial intentions that fit with empirical data. Family support has a positive and very significant effect on entrepreneurial intentions, the need for achievement does not affect an entrepreneurial orientation, and entrepreneurial orientation has a positive and very significant impact on entrepreneurial intentions. This research implies that this model can be used as a reference and applied to overcoming economic problems in vulnerable groups.