bluuebunny/crossref_metadata_2025 huggingface dataset:
Leveraging HLS to Design a Versatile & High-Performance Classic McEliece Accelerator
Authors: Kostalabros Ioannis-Vatistas , Ribes Jordi , Carril Xavier , Farras Oriol , Hernandez Carles , Moreto Miquel
Published: October 2024

By harnessing fundamental quantum properties, a large-scale quantum computer could undermine currently deployed public-key algorithms. The post-quantum, code-based cryptosystem Classic McEliece (CM) addresses this security concern. However, its large public key size (up to 1.3MB) poses various hardware implementation challenges. In this paper, we focus on the high memory bandwidth requirements of the CM encoding function, in the context of heterogeneous CPU-FPGA devices. More concretely, we target the acceleration of public-key loading and processing from any globally-shared or accelerator-private memory system. We present a novel and constant-time accelerator
eEnc
that exploits the elevated parallelization potential of FPGA devices to yield high-performance results. Our accelerator implements the encoding and the random error vector generation functions, which comprise the main computational load of Encapsulation. Two accelerator design variants are introduced, providing different hardware tradeoffs. Regarding intra-accelerator data communication, and unlike other state-of-the-art (SOTA) works, we combine a streaming protocol with task-level parallelization to remove the need to store the public key in accelerator-private memories. Our proposed design shows new record execution times over its SOTA counterparts, ranging on average from 3.5 × up to 7.7 × across the five security level parameter sets. Our end-to-end implementation in a Zynq SoC shows an average speedup of 2.2 × compared to a 64-bit vectorized CM software-baseline. The elevated logic resource consumption, characteristic of HLS designs, can be readily adjusted with a performance tradeoff.
Clarifying the Relationship Between Chemical States of P in Fe–P Alloys and Pitting Corrosion Resistance
Authors: Takayama Riku , Nishimoto Masashi , Sato Haruka , Muto Izumi
Published: October 2024

Fe–0.002 P, Fe–0.05 P, Fe–0.2 P, and Fe–2 P alloys (numbers indicate the mass%) were fabricated, and their pitting potentials, depassivation pH values, and active dissolution rates were measured. The order of pitting potentials was (high) Fe–0.002 P ≥ Fe–0.05 P ≥ Fe–0.2 P ≫ Fe–2 P (low), and that of depassivation pH values was (low) Fe–0.002 P ≤ Fe–0.05 P ≤ Fe–0.2 P ≪ Fe–2 P (high). Both parameters changed significantly between the Fe–0.2 P and Fe–2 P alloys. No evidence of grain boundary segregation of P was observed in the Fe–0.05 P alloy. In the Fe–0.2 P alloy, grain boundary segregation of P was observed, but no pitting occurred at the grain boundaries. In the Fe–2 P alloy, Fe3P precipitated at the grain boundaries and in grains, but pitting corrosion occurred in the alloy matrix and not in Fe3P. This indicated that P in the solid solution was the main cause of the decrease in pitting corrosion resistance. The P concentration in the surface oxide film on Fe–2 P was higher than that on Fe–0.2 P, and the P in the films was determined to be FePO4. The decrease in the pitting resistance with an increasing P concentration was due to FePO4.
A Comparative Study of the Linear/Nonlinear Optical, and Dielectric Properties of PVA/CMC/(1−x)ZnWO4−xPbS Blended Polymers for Optoelectronic Applications
Authors: Mohamed Mohamed Bakr , Heiba Zein K. , El-naggar A. M. , Kamal A. M. , Lakshminarayana G.
Published: October 2024

An analysis was conducted on the optical, structural, and dielectric characteristics of PVA/CMC/(1−x)ZnWO4/xPbS blends. The structures of the filler samples, undoped, and doped blends were examined using X-ray diffraction. The crystallite sizes of the various phases in the filler samples are affected by the amount of PbS in the nanocomposite. The morphologies of different blends were explored using scanning electron microscopy. The doped blend exhibited superior absorption of Ultraviolet A (UVA) and Ultraviolet B (UVB) types in addition to the visible spectrum. The optical band gaps were minimized to (5.37, 5.56, 4.11) and (4.76, 3.14, 2.92) eV for direct and indirect optical transitions, respectively, when the PVP/CMC doped with nanocomposite had 10% PbS. The highest refractive index, optical dielectric constant,and nonlinear optical parameter values were achieved when the blend was loaded with ZnWO4 only while the highest optical conductivity was obtained as the blend contained 15% PbS. The highest fluorescence intensity was observed when the fillers did not contain PbS, and it decreased as the concentration of PbS in the filler increased.
Sensorimotor adaptation to a nonuniform formant perturbation generalizes to untrained vowels
Authors: Parrell Benjamin , Niziolek Caroline A. , Chen Taijing
Published: October 2024

We show that sensorimotor adaptation of vowels at the edges of the articulatory working space generalizes to intermediate vowels through local transfer of learning from adjacent vowels. These results extend findings on the locality of sensorimotor learning from upper limb control to speech, a complex task with an opaque and nonlinear transformation between motor actions and sensory consequences. Our results also suggest that our paradigm has potential to drive behaviorally relevant changes that improve communication effectiveness.
Role of the Kölliker–Fuse/parabrachial complex in the generation of postinspiratory vagal and sympathetic nerve activities and their recruitment by hypoxemic stimuli in the rat
Authors: Toor Rahat Ul Ain Summan , Burke Peter G. R. , Dempsey Bowen , Sun Qi-Jian , Hildreth Cara M. , Phillips Jacqueline K. , McMullan Simon
Published: October 2024

Inhibition of neurons in the pontine Kölliker–Fuse/parabrachial complex (KF-PBN) differentially inhibited postinspiratory (post-I) activity in vagal and sympathetic outputs. The strong recruitment of post-I vagal activity that occurs in response to hypoxemia is selectively abolished by KF-PBN inhibition. This suggests that 1) post-I activity in vagal and sympathetic outputs may be generated by partially independent mechanisms and 2) neurons in the KF-PBN are a preeminent source of drive for the generation of eupneic post-I activity.
Are Women’s Breast Cancer Risk Appraisals in Line with Updated Clinical Risk Estimates Communicated? Results from a UK Family History Risk and Prevention Clinic
Authors: Woof Victoria G. , Howell Anthony , Fox Lynne , McWilliams Lorna , Evans Dafydd Gareth R. , French David P.
Published: October 2024

Background:

The incorporation of breast density and a polygenic risk score (PRS) into breast cancer risk prediction models can alter previously communicated risk estimates. Previous research finds that risk communication does not usually change personal risk appraisals. This study aimed to examine how women from the family history risk study appraise their breast cancer risk following communication of an updated risk estimate.

Methods:

In the family history risk study, 323 women attended a consultation to receive an updated breast cancer risk estimate. A subset (n = 190) completed a questionnaire, assessing their subjective breast cancer risk appraisals, satisfaction with the information provided, and cancer-related worry. One hundred and three were notified of a decreased risk, 34 an increased risk, and 53 an unchanged risk.

Results:

Women’s subjective risk appraisals were in line with the updated risk estimates provided, with age, a PRS, and breast density explaining most of the variance in these appraisals. Those notified of an increased risk demonstrated higher subjective risk perceptions compared with those whose risk remained unchanged or decreased.

Conclusions:

Women’s subjective breast cancer risk appraisals are amenable to change following updated risk feedback, with new information breast density and a PRS accepted and integrated into existing risk appraisals. Trust in the service, the analogies, and visual communication strategies used may have positively influenced the integration of this new information.

Impact:

Further research is warranted to assess whether similar patterns emerge for other illnesses and in different clinical contexts to determine the best strategies for communicating updated risk estimates.
Exploring the Impact of Sarcopenia on Mortality in Breast Cancer Patients: A Comprehensive Systematic Review and Meta-Analysis
Authors: Dai YanYan , Lan Jiarong , Li Shasha , Xu Guangxing
Published: October 2024

Background: This study assesses the frequency of sarcopenia in patients with breast cancer (BC) and its association with mortality rates. Methods: An all-encompassing search across (PubMed, Scopus, Web of Science, and CINAHL) was done, to identify studies, published until August 2023, that report data on sarcopenia and mortality in BC patients. A meta-analysis was then done using a random-effects model. Results: Out of 989 initially identified potential studies, 19 met inclusion criteria. Analysis of 15 studies showed a rate of sarcopenia of 38% (95% CI: 29–48%), with moderate heterogeneity (I2 = 25.8%). Sarcopenia was linked to increased mortality risk in BC patients across 16 studies (HR: 1.77, CI: 1.35–2.32, p = <0.001) with both shorter and longer follow-up periods. Similarly, mortality risks were significantly higher in metastatic (HR: 1.52, CI: 1.14–2.03, p = 0.004) and non-metastatic (HR: 2.55, CI: 1.66–3.93, p < 0.001) BC patients with sarcopenia. Conclusion: Our analysis demonstrates a substantial prevalence of sarcopenia in BC patients. Importantly, sarcopenia was significantly linked to an elevated risk of mortality in this population. Subgroup analyses, stratified by follow-up periods and disease stage, consistently reveal increased mortality risks associated with sarcopenia, underscoring its clinical relevance in both short- and long-term patient outcomes. Our findings further strengthen the need to recognize and address sarcopenia as a critical factor in BC management and prognosis.
Periodic Paralysis: A Case Series with a Literature Review
Authors: Al Hariri Bassem , Hassan Muad Abdi , Sharif Muhammad , Alsakaji Obada Adel , Hassan Yussuf Abdi , Khalid Muayad Kasim
Published: October 2024

Introduction: Periodic paralysis is a condition that causes recurrent episodes of flaccid paralysis, and it can be primary or secondary. Hypokalemic periodic paralysis is the most common type of primary periodic paralysis, and it is inherited through autosomal dominant gene transmission. Males are affected three times more often than females, and the paralysis attacks usually occur at night after a period of vigorous exercise. It is crucial to exclude other diagnostic entities based on the nature of presentation, physical examination, and paraclinical studies. Thyrotoxic periodic paralysis is more prevalent in Asian or Hispanic males with thyrotoxicosis, where up to 10% of thyrotoxic patients may experience periodic paralysis. Case Presentations: Here, we present 6 cases of patients who came to our care with varying degrees of muscle weakness, each showing interesting and diverse laboratory results. Conclusion: In patient assessment, it is crucial to consider social and family history. Even without this information, awareness of potential diagnoses is vital. The cause should be carefully considered for possible simple treatments. Failing to recognize and address this condition promptly could lead to severe outcomes. Timely identification and intervention are essential for effective disease management and patient welfare.
The Parental Centromere Sizes Remain Unaltered in Allopolyploid Wheat-Rye Hybrids
Authors: Evtushenko Elena V. , Gatzkaya Sima S. , Stepochkin Petr I. , Vershinin Alexander V.
Published: October 2024

Introduction: In chromatin nucleosomes, the presence – instead of canonical histone H3 – of its variant, CENH3 (in plants), is considered the most reliable marker of the location of centromeres. In this study, we investigated the effects of distant hybridization and maternal cytoplasm on centromere size in allopolyploid hybrids between wheat and rye as compared to their parental forms. Methods: Centromere sizes were measured using 2D images of CENH3 fluorescent signals on interphase nuclei obtained from parental forms and a triticale hybrid (genomic formula AABBBRR), in which the maternal form is wheat and secalotriticum hybrids (genomic formula RRAABBB) in which the maternal form is rye. For measurements, we selected the largest spherical nuclei with large nucleoli in the late G2 phase, in which most of the loading of CENH3 into centromeric chromatin takes place. Results: When processing the results of the measurement of centromere sizes in the hybrids, the obtained values were compared with those expected for the case of no change in centromere sizes in any of the parental sets of chromosomes. We found no significant differences between expected and measured values. Conclusion: We believe that, in the case of allopolyploid hybrids between wheat and rye, centromeres of chromosomes from the parental species retain the sizes formed during evolution. This conservatism may be promoted by the high similarity in the structure of the CENH3 molecules between these species.
A holistic approach of stability using material parameters of manipulators
Authors: Mustary Shabnom , Kashem Mohammod Abul , Chowdhury Mohammad Asaduzzaman , Uddin Jia
Published: October 2024

The demand for a comprehensive method to assess stability using manipulator material parameters is high. Various material parameters, such as the Young modulus, which represents stiffness, damping, and deflection, influence the material of the robot manipulator. The correlation between robot stability and these characteristics remains unclear, as prior studies have not yet examined the collective impact of these parameters on robot manipulators. This work considers two sophisticated manipulators, namely ABB and FANUC. The main objective of this research is to construct a stability model that considers the material properties of stiffness, damping, and deflection to assess the manipulator’s stability level, which may be categorized as low, medium, or high. Furthermore, the presented stability model examines and employs numerous modified and conventional formulas for material properties to determine the level of stability. The findings show that stiffness significantly influences the stability of robot manipulators, a relationship that applies to all the examined manipulators. We also emphasize that the choice of manipulator materials significantly impacts stability maintenance. These findings are expected to enhance the design and advancement of novel robot manipulators within the industry.
Use of artificial intelligence in banknote reconstruction
Authors: Wu Yi-Chang , Chiang Pei-Shan , Liu Yao-Cheng , Huang Ru-Yi
Published: October 2024

Banknotes may be damaged during various events, such as floods, fires, insect infestations, and mechanical or manual shredding. Disaster victims might need to perform banknote reconstruction when applying for currency exchange, or investigative agencies might need to conduct such reconstruction during evidence collection. When the number of banknote fragments is small, they can be manually assembled; however, when this number is large, manual assembly becomes increasingly difficult and time-consuming. Therefore, an automated and effective method is required for banknote reconstruction. The process of banknote reconstruction can be considered similar to solving a large-scale jigsaw puzzle. This study employed an artificial intelligence (AI) system to reconstruct damaged banknotes. A robotic arm was used to replace manual separation and automated digital image processing techniques, and AI image registration technology, deep learning, and logical operations were utilized. A deep convolutional neural network was used to estimate the relative homography between images, and fragmented banknotes were mapped to a reference banknote for image transformation, thereby reconstructing the damaged banknotes. Additionally, a repetitive matching method was established to optimize the matching results to achieve the best possible mapping and enhance validation efficiency.
Design and development of knee rehabilitation robot
Authors: Sharma Devashish , Shaik Sahil Ahamed , Rajagopal Saran , Mohan Manju , Ramanathan Kuppan Chetty , Lingampally Pavan Kalyan
Published: October 2024

This research presents a comprehensive design and analysis of a knee rehabilitation platform aimed at aiding individuals with knee dysfunction. Dysfunction in the knee joint can lead to an imbalance in gait and posture during activities of daily living (ADLs) such as standing, walking, and running. This study focuses on developing a 2-degree-of-freedom (2-DoF) knee rehabilitation device capable of mimicking linear and angular movements. A slider mechanism-based knee rehabilitation device is developed and simulated alongside various other mechanisms. The proposed mechanism achieves 32.5° of flexion for a linear movement of 0.45 m within 6 seconds, outperforming other mechanisms. To validate simulation results, a 3D-printed model is fabricated, and experimental studies are conducted under no-load conditions, showing close alignment with simulation outcomes with a deviation of ±5%. The device’s key features include portability, compliance, compactness, and enhanced stiffness. Future research will involve conducting pilot studies to further evaluate the practical efficacy and potential enhancements of the proposed knee rehabilitation platform.
Adjusted linear quadratic regulator-proportional-derivative control of Quanser’s three degrees of freedom helicopter based on flower pollination algorithm under external disturbances
Authors: Ghiloubi Imam Barket , Abdou Latifa , Lahmar Oussama
Published: October 2024

External disturbances, saturation of actuator motors, and limits of certain angular movements are commonly encountered in robotic systems, particularly those involving flight, and they present the most common and influential factors affecting the stability and performance of these systems. In this paper, a hybrid controller for a three-degree-of-freedom (3-DoF) helicopter is designed and applied to this flying robot system, taking into account the previously mentioned constraints. The proposed hybrid controller integrates proportional-derivative (PD) control with an adjusted linear quadratic regulator (ALQR) using the flower pollination algorithm (FPA) optimization method. Simulation results of travel (λ), elevation (ε), and pitch (ρ) responses, as well as experimental results of elevation and travel tracking responses under external disturbances using the bench-top Quanser’s (3-DoF) helicopter, demonstrate the robustness and good performance of the controlled system using the proposed method. The effectiveness of the proposed method is compared to several methods in the literature.
Vision-based approach for human motion detection and smart appliance control
Authors: Swami Siddharth , Singh Rajesh , Gehlot Anita , Iqbal Mohammed Ismail , Sharma Sameer Dev , Kumar Dharmendra , Shah Sanjeev Kumar
Published: October 2024

This study focuses on the use of computer vision technology and motion detection sensors to create an intelligent system that recognizes human presence in monitored spaces. The system uses a relay module for automation and control of household appliances while sensing motion detection, operated by an ESP32 microcontroller. This innovative solution addresses two major issues in home automation: reliable human presence recognition and seamless appliance control. The research merges a camera-based vision system with motion sensors, comparing motion and vision-based identification. The ESP32 microcontroller improves motion detection precision and context awareness by integrating motion sensors and computer vision technologies. The integration of a camera module allows real-time analysis and recognition of human presence, reducing false alarms. The relay module also enables automated control of home appliances, synchronizing and feedbacking operations with sensed human presence. The dynamic adaptation of the system improves user convenience and energy efficiency.
Faults-as-address simulation
Authors: Hahanov Vladimir , Chumachenko Svetlana , Litvinova Eugenia , Hahanov Ivan , Ponomarova Veronika , Khakhanova Hanna , Kulak Georgiy
Published: October 2024

Fault-as-address-simulation (FAAS) is a simulation mechanism for testing combinations of circuit line faults, represented by the bit addresses of element logical vectors. The XOR relationship between the test set T and the truth table L of the element forms a deductive vector for fault simulation, using truth table addresses or the logic vector bits. Addresses are used in the simulation matrix to mark those n-combinations of input faults detected at the element's output. The columns of the simulation matrix are treated as n-row addresses to generate an element output row via a deductive vector. There is no transport of input faults to the element output, Only the 1-signals written in the non-input row coordinates of the circuit simulation matrix. The simulation matrix is initially filled with 1-signals along the main diagonal. The line faults detected on the test set of circuits are determined by the inverse of lines good values, which have 1-values in the matrix row corresponding to the output circuit element. The deductive vector is obtained by the XOR-relations between the test set and logical vector in three table operations. The advantage of the proposed FAAS mechanism is the predictable complexity of the algorithm and memory consumption for storing data structures when simulating a test set.
An introduction to using QR codes in web portals for synchronizing calendar events over phones
Authors: Sethi Inder Pal Singh , Gupta Om Pradyumana , Bhaisare Sulbha , Dwivedi Ritesh Kumar , Kapoor Misha
Published: October 2024

An optical label with machine-readable information about the object it is attached to is called a quick response (QR) code. QR codes frequently hold information for a tracker, locator, or identifier that directs users to a website or application. To efficiently store data, a QR code has four standardized encoding modes: kanji, byte or binary, alphanumeric, and numeric. As a means of identifying a wide range of commercial goods, including transactions, ads, and other public notices, the QR code gained popularity. In our web portal, the proposed QR code model synchronizes all the event details synchronously in the mobile calendar. QR code is used for web-to-mobile data transfer, saving events or meeting details in the mobile calendar. Anyone with a smartphone can view the data encoded in a QR code by scanning it. Although it makes it easier for end users to decode QR codes, verifying access to the encoded data is a cause for worry. Our proposed model validates access to data through the QR code, allowing only authorized personnel to access data. To ensure accessibility control, the proposed model has the functionality of a one-time password (OTP) that enhances application security. The model achieved an average decoding speed of 157 milliseconds with an error rate of 0.38%.
Analysis of single layer artificial neural network neuromorphic hardware chip
Authors: Pant Aruna , Kumar Adesh , Kuchhal Piyush
Published: October 2024

The neuromorphic architectures are hardware network systems designed with neural functions. Neural networks seen in biology serve as an inspiration for network systems. A synapse connects every node or neuron in an artificial neural network (ANN) to every other node. As in biological brains, the amplitude of the linking between nodes referred to as synaptic weights will regulate the connection. In contrast to conventional design, ANN uses many highly organized dealing pieces that work together to solve real-world issues. The design of the neuromorphic hardware chip is discussed in the paper. The target device used is a Virtex-5 Field Programmable Gate Array (FPGA) and the simulation is taken on Xilinx ModelSim software. This chip is designed for 20 neuron inputs, each of the neuron inputs is 8-bit. Each 20-neuron input is multiplied by 20 input weights and each weight is 8-bit so when these 20 input weights are multiplied by 20 neuron inputs in the multiplier it gives 16-bit output. A control logic is used in this neuromorphic hardware chip design which is used to feed multiplier output to each input of the hidden layer. The system-level outcome of the hidden layer is then given to the multiplexer which has 20 inputs and one single output. The multiplexer is used to select any of the 20 outputs of the control logic. Finally, to gain an understanding of the performance of this neuromorphic hardware chip, we have computed the hardware utilization parameters. These parameters include slices, input/output blocks (IOBs), registers used, memory, and the overall propagation delay used by the hardware chip.
Fuzzy logic assessment of X-ray tube risks in robotic C-arm angiography: a failure mode and effect analysis study
Authors: Firdaus Ade , Adriansyah Andi , Ferdana Nanda , Suhartina Rahmalisa , Surakusumah Rino Ferdian , Haekal Jakfat , Zulhamidi Zulhamidi , Shamsudin Abu Ubaidillah
Published: October 2024

This research examines the integration of robotic C-arm technology in angiography, a critical tool for treating cardiac conditions. The robotic C-arm, which includes an X-ray tube, is essential for scanning patients during procedures. The study also investigates the associated risks, specifically in Indonesian hospitals with cardiac facilities. Angiography is used to diagnose and treat heart disease by visualizing blood vessels and facilitating catheterization procedures. However, its mobility poses hazards and can impact the process. To address potential risks, failure mode and effect analysis (FMEA) is utilized. Traditionally, risk assessment using risk priority numbers (RPN) is conducted, but these may not accurately reflect failures due to complex evaluating processes. To overcome this limitation, fuzzy logic is employed, enhancing risk assessment accuracy. Through this approach, twenty-seven failure modes are identified across two brands, with ten major ones prioritized using fuzzy logic. These findings facilitate the development of preventive measures to mitigate future failures and enhance patient safety during angiography in hospitals. In conclusion, the study underscores the importance of robust risk management in medical equipment, particularly in dynamic environments. By integrating fuzzy logic into risk assessment, the study improves prioritization accuracy, enabling effective allocation of resources for preventive actions.
Do sertão da Bahia a Toronto: a trajetória profissional da enfermeira diplomada Haydée Guanais Dourado (1931-1942)
Authors: Ferreira Luiz Otávio , Batista Ricardo dos Santos
Published: October 2024

This article analyzes part of the professional trajectory of nurse and sociologist Haydée Guanais Dourado, from her training as a primary school teacher [normalista] at Instituto Ponte Nova (Bahia, Brazil) to her joining the group of nurses at the School of Nursing at the University of São Paulo. The study is possible by recreating the contexts in which she lived and is inseparable from understanding the social characteristics of the group in which she participated, that of qualified nurses. HGD’s trajectory oscillates between similarities and singularities in relation to the professional group. The investigation uses a reduction in the scale of analysis and an intensive study of the material analyzed. Throughout HGD’s trajectory, it is concluded that a large part of Brazilian registered nurses worked in public health institutions or hospitals and a few others became intellectuals who planned higher education in nursing and reflected on the destiny of the profession.
A onda de greves em São Paulo, 1945-1946: uma abordagem quantitativa
Authors: Ferreira Fernando Sarti
Published: October 2024

Neste artigo, pretendemos apresentar algumas conclusões preliminares obtidas a partir da organização de um banco de dados sobre as greves ocorridas entre 1945 e 1946 em São Paulo, construído a partir de uma série de listas que registraram essas mobilizações e que foram produzidas pela polícia política paulista (DEOPS-SP). Na primeira seção, abordaremos algumas questões metodológicas relativas ao tratamento das fontes policiais e ao trabalho de uma perspectiva quantitativa sobre greves, ao mesmo tempo em que buscaremos expor em linhas gerais como o banco de dados foi construído. Na segunda parte, vamos expor as primeiras conclusões que surgiram a partir da análise dos dados sumarizados nessa etapa da pesquisa, destacando aqueles eventos ocorridos em 1945 e que foram menos estudados pela historiografia. Por fim, nas considerações finais, elencamos nossas principais conclusões e apontamos os próximos rumos que a pesquisa deve seguir.
Plasma Proteomic Insights for Identification of Novel Predictors and Potential Drug Targets in Atrial Fibrillation: A Prospective Cohort Study and Mendelian Randomization Analysis
Authors: Peng Xiaodong , Li Yukun , Liu Nian , Xia Shijun , Li Xin , Lai Yiwei , He Liu , Sang Caihua , Dong Jianzeng , Ma Changsheng
Published: October 2024

BACKGROUND:

Currently, there are no reliable methods for predicting and preventing atrial fibrillation (AF) in its early stages. This study aimed to identify plasma proteins associated with AF to discover biomarkers and potential drug targets.

METHODS:

The UK Biobank Pharma Proteomics Project examined 2923 circulating proteins using the Olink platform, forming the basis of this prospective cohort study. The UK Biobank Pharma Proteomics Project included a randomly selected discovery cohort and the consortium-selected replication cohort. The study’s end point was incident AF, identified using
International Classification of Diseases, Tenth Revision
codes. The association between plasma proteins and incident AF was evaluated using Cox proportional hazard models in both cohorts. Proteins present in both cohorts underwent Mendelian randomization analysis to delineate causal connections, utilizing
cis
-protein quantitative trait loci as genetic tools. The predictive efficacy of the identified proteins for AF was assessed using the area under the receiver operating characteristic curve, and their druggability was explored.

RESULTS:

Data from 38 784 participants were included in this study. Incident AF cases were identified in the discovery cohort (1894; 5.5%) within a median follow-up of 14.5 years and in the replication cohort (451; 10.6%) within a median follow-up of 14.4 years. Twenty-one proteins linked to AF were identified in both cohorts. Specifically, COL4A1 (collagen IV α-1; odds ratio, 1.11 [95% CI, 1.04–1.19]; false discovery rate, 0.016) and RET (proto-oncogene tyrosine-protein kinase receptor Ret; odds ratio, 0.96 [95% CI, 0.94–0.98]; false discovery rate, 0.013) demonstrated a causal link with AF, and RET is druggable. COL4A1 improved the short- and long-term predictive performance of established AF models, as evidenced by significant enhancements in the area under the receiver operating characteristic, integrated discrimination improvement, and net reclassification index, all with
P
values below 0.05.

CONCLUSIONS:

COL4A1 and RET are associated with the development of AF. RET is identified as a potential drug target for AF prevention, while COL4A1 serves as a biomarker for AF prediction. Future studies are needed to evaluate the effectiveness of targeting these proteins to reduce AF risk.
Essential Role of the RIα Subunit of cAMP-Dependent Protein Kinase in Regulating Cardiac Contractility and Heart Failure Development
Authors: Bedioune Ibrahim , Gandon-Renard Marine , Dessillons Matthieu , Barthou Aurélien , Varin Audrey , Mika Delphine , Bichali Saïd , Cellier Joffrey , Lechène Patrick , Karam Sarah , Dia Maya , Gomez Susana , Pereira de Vasconcelos Walma , Mercier-Nomé Françoise , Mateo Philippe , Dubourg Audrey , Stratakis Constantine A. , Mercadier Jean-Jacques , Benitah Jean-Pierre , Algalarrondo Vincent , Leroy Jérôme , Fischmeister Rodolphe , Gomez Ana-Maria , Vandecasteele Grégoire
Published: October 2024

BACKGROUND:

The heart expresses 2 main subtypes of cAMP-dependent protein kinase (PKA; type I and II) that differ in their regulatory subunits, RIα and RIIα. Embryonic lethality of RIα knockout mice limits the current understanding of type I PKA function in the myocardium. The objective of this study was to test the role of RIα in adult heart contractility and pathological remodeling.

METHODS:

We measured PKA subunit expression in human heart and developed a conditional mouse model with cardiomyocyte-specific knockout of RIα (RIα-icKO). Myocardial structure and function were evaluated by echocardiography, histology, and ECG and in Langendorff-perfused hearts. PKA activity and cAMP levels were determined by immunoassay, and phosphorylation of PKA targets was assessed by Western blot. L-type Ca
2+
current (
I
Ca,L
), sarcomere shortening, Ca
2+
transients, Ca
2+
sparks and waves, and subcellular cAMP were recorded in isolated ventricular myocytes (VMs).

RESULTS:

RIα protein was decreased by 50% in failing human heart with ischemic cardiomyopathy and by 75% in the ventricles and in VMs from RIα-icKO mice but not in atria or sinoatrial node. Basal PKA activity was increased ≈3-fold in RIα-icKO VMs. In young RIα-icKO mice, left ventricular ejection fraction was increased and the negative inotropic effect of propranolol was prevented, whereas heart rate and the negative chronotropic effect of propranolol were not modified. Phosphorylation of phospholamban, ryanodine receptor, troponin I, and cardiac myosin-binding protein C at PKA sites was increased in propranolol-treated RIα-icKO mice. Hearts from RIα-icKO mice were hypercontractile, associated with increased
I
Ca,L,
and [Ca
2+
]
i
transients and sarcomere shortening in VMs. These effects were suppressed by the PKA inhibitor, H89. Global cAMP content was decreased in RIα-icKO hearts, whereas local cAMP at the phospholamban/sarcoplasmic reticulum Ca
2+
ATPase complex was unchanged in RIα-icKO VMs. RIα-icKO VMs had an increased frequency of Ca
2+
sparks and proarrhythmic Ca
2+
waves, and RIα-icKO mice had an increased susceptibility to ventricular tachycardia. On aging, RIα-icKO mice showed progressive contractile dysfunction, cardiac hypertrophy, and fibrosis, culminating in congestive heart failure with reduced ejection fraction that caused 50% mortality at 1 year.

CONCLUSIONS:

These results identify RIα as a key negative regulator of cardiac contractile function, arrhythmia, and pathological remodeling.
Personal Genetic-Hypertension Odyssey From Phenotypes to Genotypes and Targets
Authors: Luft Friedrich C.
Published: October 2024

Hypertension requires increased systemic vascular resistance. Thus far, Mendelian hypertension–related genes are related to salt retention, an indirect regulatory effect. With the identification of mutated, overactive, PDE3A (phosphodiesterase 3A), we have uncovered a more direct vasoconstrictive mechanism. The autosomal-dominant syndrome features another specific phenotype, brachydactyly type E. Hypertension and the bony phenotype invariably occur together. We distinguished between these phenotypes by examining individual pedigrees. We implicated the gene encoding the parathyroid hormone-related peptide in the brachydactyly. We identified the hypertensive mechanisms as involving regulatory-region, gain-of-function, exon 4 rare pathogenic variants, in the cAMP-cGMP–catabolizing enzyme, PDE3A. We generated rodent models that recapitulate all human phenotypes. Comparisons not only allowed pathogenic insights into the human condition but also provided intervention models. Moreover, we identified rare pathogenic variants in exon 13 encoding the enzymatic pocket. These patients had identical phenotypes, also corroborated in a rodent model, which produced the same human phenotypes. These data could allow the differentiation between a target organ and blood pressure phenotype. The research allows visualization of enzymatic processes at the intracellular nanodomain level. The scope of this project has elucidated genetic mechanisms important to cartilage development, possibly cancer metastases, and findings relevant to cardiovascular regulation via systemic vascular resistance. For our team, the project was an educational/scientific adventure over a professional lifetime.
Life’s Essential 8 Trajectories and Risk of Stroke: A Prospective Cohort Study
Authors: Liu Yang , Qin Xueying , Jiang Jinguo , Zhao Maoxiang , Peng Xinyi , Cui Feipeng , Wang Xianxuan , Feng Jun , Chen Shuohua , Wu Shouling
Published: October 2024

BACKGROUND:

Evidence is lacking regarding long-term patterns of change in Life’s Essential 8 (LE8) and their association with the risk of stroke. We aim to evaluate LE8 trajectories and examine their association with the risk of stroke in China.

METHODS:

This study, conducted in a workplace setting, recruited 26 719 participants (average age, 46.02±11.27 years and a male population of 73.73%) who had no history of stroke and consecutively participated in 6 surveys from 2006 to 2016. Repeated LE8 measurements were determined by taking the unweighted average of the 8 component scores ranging from 0 to 100. People with higher scores had better overall cardiovascular health. By examining the medical records of the participants, stroke cases were identified for the period from 2016 to 2020. A latent mixture model was applied to classify the trajectory clusters of LE8 from 2006 to 2016, and Cox proportional hazard models were used to analyze the data.

RESULTS:

Five LE8 trajectories were detected between 2006 and 2016. Four hundred ninety-eight incident strokes including 55 (11.04%) hemorrhagic and 458 (91.97%) ischemic strokes were documented. After adjusting for covariates, the hazard ratios and 95% CIs for the association between stable-low, moderate-increasing, moderate-stable, and high-stable trajectories and incident stroke, compared with the moderate-decreasing trajectory, were 1.42 (1.11–1.84), 0.73 (0.56–0.96), 0.49 (0.39–0.62), and 0.19 (0.11–0.32), respectively. Individuals with high LE8 status (LE8≥80) exhibited a significantly reduced risk of stroke compared with those with low one (LE8≤49;
P
-trend <0.001). A faster annual growth in LE8 was related to a lower risk of stroke.

CONCLUSIONS:

Maintaining high LE8 over an extended period and high baseline LE8 status were related to a decreased risk of stroke. Despite the initial low level of LE8, improvement in LE8 attenuates or even reverses the risk of stroke.
Incidence and Outcomes of Patients With Early Cardiac Complications After Intracerebral Hemorrhage: A Report From VISTA
Authors: Ishiguchi Hironori , Huang Bi , El-Bouri Wahbi K. , Dawson Jesse , Lip Gregory Y.H. , Abdul-Rahim Azmil H. , Lees K.R. , Alexandrov A. , Bath P.M. , Bluhmki E. , Bornstein N. , Chen C. , Claesson L. , Curram J. , Davis S.M. , Diener H-C. , Donnan G. , Fisher M. , Ginsberg M. , Gregson B. , Grotta J. , Hacke W. , Hennerici M.G. , Hommel M. , Kaste M. , Lyden P. , Marler J. , Muir K. , Roffe C. , Sacco R. , Shuaib A. , Teal P. , Venketasubramanian N. , Wahlgren N.G. , Warach S.
Published: October 2024

BACKGROUND:

The incidence and outcomes of early cardiac complications in patients with intracerebral hemorrhage (ICH) are poorly understood. These cardiac complications may be part of the so-called stroke-heart syndrome in patients with ICH. We investigated this issue in an individual patient data pooled analysis from an international repository of clinical trial data.

METHODS:

We used the Virtual International Stroke Trials Archive to investigate the incidence of cardiac complications within 30 days post-ICH or acute ischemic stroke (AIS). These complications included acute coronary syndrome encompassing myocardial injury, heart failure/left ventricular dysfunction, atrial fibrillation/atrial flutter, other arrhythmia/ECG abnormalities, and cardiorespiratory arrest. We used propensity score matching to compare the incidence of patients with stroke-heart syndrome in patients with ICH with those following AIS. Factors associated with 90-day mortality were evaluated using multivariate logistic regression analysis in the ICH cohort.

RESULTS:

We pooled data from 8698 participants recruited in acute stroke trials (mean age, 68±12 years; 56% male), of whom 914 (11%) were patients with ICH. Among the patients with ICH, 123 (13%) had stroke-heart syndrome in patients with ICH. Following propensity score matching, a total of 1828 patients (914 for each of the cohorts) were analyzed. While the overall incidence of cardiac events tended to be lower in the ICH group compared with the AIS group (the cumulative incidence freedom from the event, 86.3% [95% CI, 84.1–88.6] versus 83.6% [95% CI, 81.2–86.0];
P
=0.100), the incidences cardiac events other than atrial fibrillation/atrial flutter were comparable between the 2 matched groups. The incidence of atrial fibrillation/atrial flutter was significantly lower in the ICH group than in the AIS group (
P
<0.001). The multivariate-adjusted analysis found that stroke-heart syndrome in patients with ICH was associated with 90-day mortality (adjusted odds ratio, 1.12 [95% CI, 1.06–1.19];
P
<0.001).

CONCLUSIONS:

Cardiac events are common and negatively affect prognosis in patients with ICH, just as seen in AIS.
Association of Anticoagulant Use With Hemorrhage Location and Etiology in Incident Spontaneous Intracerebral Hemorrhage
Authors: Wilson Mitch , Incontri Diego , Vu Stephanie , Marchina Sarah , Wang Jia-Yi , Andreev Alexander , Heistand Elizabeth , Carvalho Filipa , Selim Magdy , Lioutas Vasileios-Arsenios
Published: October 2024

BACKGROUND:

It is unknown whether hypertensive microangiopathy or cerebral amyloid angiopathy (CAA) predisposes more to anticoagulant-associated intracerebral hemorrhage (AA-ICH). The purpose of our study was to determine whether AA-ICH is associated with lobar location and probable CAA.

METHODS:

This was a cross-sectional analysis of patients with first-ever spontaneous ICH admitted to a tertiary hospital in Boston, between 2008 and 2023. Univariable and multivariable logistic regression were used to investigate the association between anticoagulation use and both lobar hemorrhage location and probable CAA on magnetic resonance imaging (MRI) by Boston Criteria 2.0 or computed tomography by Simplified Edinburgh Criteria.

RESULTS:

A total of 1104 patients (mean [SD] age, 73 [12]; 499 females [45.0%]) were included. Of the 1104 patients, 268 (24.3%) had AA-ICH: 148 (55.2%) with vitamin K antagonists and 107 (39.9%) with direct oral anticoagulants. Brain MRI was performed in 695 (63.0%) patients. The proportion of patients with lobar hemorrhage was not different between those with and without AA-ICH (121/268 [45.1%] versus 424/836 [50.7%]; odds ratio [OR], 0.80 [95% CI, 0.61–1.05];
P
=0.113). Patients with AA-ICH were less likely to have probable CAA on MRI (17/146 [11.6%] versus 127/549 [23.1%]; OR, 0.44 [95% CI, 0.25–0.75];
P
=0.002) and probable CAA on MRI or computed tomography if MRI not performed (27/268 [10.0%] versus 200/836 [23.9%]; OR, 0.36 [95% CI, 0.23–0.55];
P
<0.001). Among patients with AA-ICH, there were no differences in the proportion with lobar hemorrhage (63/148 [42.6%] versus 46/107 [43.0%]; OR, 1.02 [95% CI, 0.62–1.68];
P
=0.946) or probable CAA on MRI (10/72 [13.9%] versus 7/69 [10.1%]; OR, 0.70 [95% CI, 0.25–1.96];
P
=0.495) between vitamin K antagonists and direct oral anticoagulant users.

CONCLUSIONS:

AA-ICH was not associated with lobar hemorrhage location but was associated with reduced odds of probable CAA. These results suggest that hypertensive microangiopathy may predispose more toward incident AA-ICH than CAA and emphasize the importance of blood pressure control among anticoagulant users. These findings require replication in additional cohorts.
Activity in Occipito-Temporal Cortex Is Involved in Tool-Use Planning and Contributes to Tool-Related Semantic Neural Representations
Authors: Thibault Simon , Koun Eric , Salemme Romeo , Roy Alice C. , Boulenger Véronique , Brozzoli Claudio
Published: October 2024

Tool use and language are highly refined human abilities which may show neural commonalities due to their potential reciprocal interaction during evolution. Recent work provided evidence for shared neural resources between tool use and syntax. However, whether activity within the tool-use network also contributes to semantic neural representations of tool nouns remains untested. To this aim, we identified the tool-use planning network with functional magnetic resonance imaging while participants used pliers. The very same participants underwent a semantic priming task including two categories, tool nouns and animal nouns, to highlight the respective underlying networks. With multivariate analyses of the activation neural patterns, we tested whether activity in tool-use brain clusters takes part in the neural representation of tool nouns as compared with animal nouns. The results revealed that word semantic categories were decoded within the left occipito-temporal cortex activated by preparing to use a tool, with similar patterns of brain activity for words within the same category. In addition, in the same area, neural activations for tool nouns were found to be higher than those for animal nouns. These findings suggest that activity in tool-use related brain areas encodes semantic information separately for tool nouns and animal nouns, thus supporting the embodiment of tool-noun processing in the tool-use sensorimotor network.
Arts-based analysis of conservation education field trips for young people to observe wild lemurs in Southern Madagascar
Authors: Walker-Bolton Amber D. , Ralison Doria , Milliasse Ramanorintsoa F.
Published: October 2024

Opportunities for young people to directly experience nature can have positive impacts on the individual, the social group and on society as a whole, through future increased conservation action. We developed a program which engaged young people from Fort Dauphin in a field trip to see wild animals at Nahampoana Reserve. Our aim in offering field trips to young people living in the city was to create a positive emotional opportunity to engage directly with nature with the ultimate goal of protecting lemurs and their habitat. In our analysis, we predicted that participants who completed a survey after a presentation and field trip (assessment post field trip) would recall more correct and detailed facts than those participants who completed their surveys after the presentation only (assessment pre field trip). Our program used a variety of arts-based data collection methods including an initial essay writing component on conservation of lemurs and drawing analysis of observed plants and animals. Our results show, in part, that (A) initial written essays by participants showed misperceptions about lemurs, (B) participants who had attended the field trip prior to drawing their favourite aspect of the reserve, produced more species-specific plant depictions, and (C) participants who were involved in a presentation, field trip, and final group discussion came up with four principles for protecting lemurs and their environment. Upon analysis after the study, we gained the additional insight of being able to evaluate our survey methods.
Reclaiming Eros: Plotinus’ Metaphysics of Love
Authors: Weiss Sonja
Published: October 2024

The paper offers a critical perspective on some modern studies of Plotinus’ doctrine of Love, which interpret his Eros as more than a guide, leading the soul to the intelligible world and above, to the first Principle, or directing its gaze to the sensible world. They consider Love to be the driving force behind generation from the One and even identify it with the One itself, basing most of their arguments on rare instances of Eros’ appearance at levels above the soul and using an emphatically erotic terminology that is alien to Plotinus.