bluuebunny/crossref_metadata_2025 huggingface dataset:
The UNICA sleep HRV analysis tool: an integrated open-source tool for heart rate variability analysis during sleep
Authors: Sattar Parisa , Baldazzi Giulia , Puligheddu Monica , Pani Danilo
Published: January 2025

Heart rate variability (HRV) analysis during sleep plays a key role for understanding autonomic nervous system function and assessing cardiovascular health. The UNICA Sleep HRV analysis (UNICA-HRV) tool is a novel, open-source MATLAB tool designed to fill the gap in current HRV analysis tools. In particular, the integration of ECG and HRV data with hypnogram information, which illustrates the progression through the different sleep stages, eases the computation of HRV metrics in polysomnographic recordings. This integration is crucial for accurate phase-specific analysis, as autonomic regulation changes markedly across different sleep stages. The tool supports single- and multiple-subject analyses and is tailored to enhance usability and accessibility for researchers and clinicians without requiring extensive technical expertise. It implements and supports a variety of data inputs and configurations, allowing for flexible, detailed HRV analyses across sleep stages, employing classical and advanced metrics, such as time-domain, frequency-domain, non-linear, complexity, and Poincaré plot indexes. Validation of the tool against established tools like Kubios and PhysioZoo indicates its robustness and precision in generating reliable HRV metrics, that are essential not only for sleep research, but also for clinical diagnostics. The introduction of UNICA-HRV represents a significant simplification for sleep studies, and its open-source nature (licensed under a Creative Commons Attribution 4.0 International License) allows to easily extend the functionality to other needs.
3D fluid simulation of the propagation of a nanosecond discharge in air above a liquid surface: investigation of the pattern formation under various conditions and comparison with experiments
Authors: Herrmann Antoine , Davignon Augustin , Margot Joëlle , Hamdan Ahmad
Published: January 2025

Plasma-liquid interaction remains one of the fundamental processes influencing the various applications. Understanding the influence of external parameters on discharge properties, particularly the discharge dynamic at the liquid surface, is therefore essential. In previous studies, we investigated the impact of voltage polarity, gap distance, and liquid dielectric permittivity and electrical conductivity on nanosecond discharges initiated in air at atmospheric pressure in a pin-to-liquid configuration. Herein, we present a 3D fluid model, improved with stochastic photoionization, to simulate the discharge dynamics under the previously mentioned conditions. The model outputs are compared with the discharge dynamics measured experimentally. For instance, filamentation and the homogeneous emission over solution’s surface measured in positive and negative discharges, respectively, are well reproduced by the simulation. Furthermore, the simulation allowed us to report other plasma properties not accessible experimentally such as the spatio-temporal distributions of electric field (E-field) and electron density. Notably, we observe that the E-field at the front of the negative surface ionization wave (SIW) is nearly four times lower than that of the positive SIW, which may explain the absence of filaments for negative discharges. Furthermore, we find that increasing solution conductivity or gap distance reduce the radial propagation velocity of the circular SIW front and stopping its expansion before a destabilization can occur. The simulation allowed investigating the influence of photoionization strength, and we find that increasing the number of ionizing photons leads to suppress the filamentation while keeping the ionization front circular and propagating at high speed.
Scalable superconductor neuron with ternary synaptic connections for ultra-fast SNN hardware
Authors: Karamuftuoglu Mustafa Altay , Ucpinar Beyza Zeynep , Fayyazi Arash , Razmkhah Sasan , Kamal Mehdi , Pedram Massoud
Published: January 2025

A novel high-fan-in differential superconductor neuron structure designed for ultra-high-performance spiking neural network (SNN) accelerators is presented. Utilizing a high-fan-in neuron structure allows us to design SNN accelerators with more synaptic connections, enhancing the overall network capabilities. The proposed neuron design is based on superconductor electronics fabric, incorporating multiple superconducting loops, each with two Josephson Junctions. This arrangement enables each input data branch to have positive and negative inductive coupling, supporting excitatory and inhibitory synaptic data. Compatibility with synaptic devices and thresholding operation is achieved using a single flux quantum pulse-based logic style. The neuron design, along with ternary synaptic connections, forms the foundation for a superconductor-based SNN inference. To demonstrate the capabilities of our design, we train the SNN using snnTorch, augmenting the PyTorch framework. After pruning, the demonstrated SNN inference achieves an impressive 96.1% accuracy on MNIST images. Notably, the network exhibits a remarkable throughput of 8.92 GHz while consuming only 1.5 nJ per inference, including the energy consumption associated with cooling to 4 K. These results underscore the potential of superconductor electronics in developing high-performance and ultra-energy-efficient neural network accelerator architectures.
Body-centered tetragonal grids for FDTD method with collocated field components and enhanced performance
Authors: Ee Ho-Seok
Published: January 2025

We present an alternative finite-difference time-domain (FDTD) scheme that utilizes a body-centered tetragonal (BCT) grid, offering spatially collocated field components and significantly improving computational performance. The update equations for the BCT-FDTD maintain the simplicity and intuitiveness characteristic of the standard FDTD based on the Yee grid, with the key distinction being that the spatial derivative in one direction requires the use of four nearest neighbors instead of two. Our analyses of dispersion and stability reveal that the BCT-FDTD achieves a relaxed stability criterion, along with reduced anisotropy and lower phase velocity errors. Numerical tests indicate that, under equal sampling density conditions, the BCT-FDTD exhibits comparable memory usage and computation time to the standard FDTD. Moreover, our analysis establishes that when using conditions that ensure a phase velocity error of less than 1%, the BCT-FDTD requires approximately 5 ×  less memory and achieves approximately 10 ×  faster computation compared to standard FDTD. This improvement is expected to be even more pronounced in simulations involving anisotropic materials, thanks to the advantages provided by spatially collocated field components. Overall, we believe that the BCT-FDTD serves as a compelling alternative to the standard FDTD.
Robust topological rainbow trapping in shamrock-leaf phononic crystal plates
Authors: Huang Yao , Zhao Jinfeng , Yuan Weitao
Published: January 2025

The topological properties of elastic waves underpin the visions of widespread novel phonon devices such as topological rainbow trapping. In this work, a shamrock-leaf perforated phononic crystal with a graded interface is designed to achieve both the topological edge states (TES) and rainbow effect together. The topological rainbow mechanism activated by varying TES along the gradient interface is uncovered, and spatial trapped waves of different frequencies are presented. Meanwhile, based on the topological rainbow effect, the wave packet behaviors encountering various types of defects at interfaces are observed. Furthermore, deviations from the original trapping position under different disturbance factors are investigated. This work provides a useful handle for piloting applications of topological phononic transports.
A numerical assessment of ocean alkalinity enhancement efficiency on a river-dominated continental shelf—a case study in the northern Gulf of Mexico
Authors: Ou Yanda , Xue Z George , Hu Xinping
Published: January 2025

A robust high-resolution coupled hydrodynamic-biogeochemical model was applied to the northern Gulf of Mexico to assess the efficiency of river- and ocean-sourced ocean alkalinity enhancement (OAE). Sensitivity tests indicate that the effectiveness of OAE-induced CO2 uptake is primarily influenced by the amount of alkalinity introduced and local wind-driven mixing, with the former determining the overall uptake and the latter affecting short-term variability. Compared to ocean-sourced OAE (direct ocean release), river-sourced OAE (elevated river alkalinity) is more effective and sustainable. River-sourced OAE has higher CO2 uptake efficiency with reduced spatial and temporal uncertainty and greater overall CO2 uptake. For river-sourced OAE, surface pH increases pronouncedly near the mouths of the Mississippi River. The ideal OAE implementation time includes spring, early summer, fall, and winter. Mid and late-summer implementation is not recommended due to weak mixing, which results in less alkalinity dispersal and greater pH variability. In addition, while the aragonite saturation state generally remains below 6 around the Mississippi River plume, it increases pronouncedly during mid to late summer, risking alkalinity loss due to CaCO3 precipitation and reduced CO2 uptake efficiency near river mouths. Scaling OAE-induced CO2 uptake to the 25 largest rivers in the world indicates that increasing riverine alkalinity concentrations by 10% could remove 23.23 megatons of CO2 annually, meeting 0.37%–0.61% of the 2025–2030 CO2 removal target.
Prey dynamics as a buffer: enhancing copepod resilience to ocean alkalinity enhancement
Authors: Bhaumik Amrita , Faucher Giulia , Henning Merle , Meunier Cédric L , Boersma Maarten
Published: January 2025

Ocean alkalinity enhancement (OAE) aims to counteract climate change by increasing the ocean’s carbon storage capacity through the addition of alkaline substances into seawater. However, this process alters seawater chemistry, increasing total alkalinity and pH, which can directly influence marine organisms’ metabolic activities or indirectly impact them through changes in prey availability and quality. This study disentangled the OAE-driven factors that might influence zooplankton physiology. We assessed the direct effects of altered chemistry on the copepod, Temora longicornis, and the indirect effects through changes in the phytoplankton prey, Rhodomonas salina. We cultured the prey under OAE conditions and used it to feed copepods to investigate the indirect effects. We found that OAE negatively impacted prey growth but improved its nutritional quality, thereby offsetting the direct negative impact of OAE on the copepod. These findings regarding OAE’s impact on prey-predator dynamics contribute to a deeper understanding of how OAE may influence zooplankton communities.
Microchannel fabrication on bio-grade Nitinol SMA by μ-ED milling process using sustainable oil for improving the machining performance and biocompatibility
Authors: Chaurasia Satish , Debnath Kishore
Published: January 2025

The process of micromachining has garnered attention for its ability to create three-dimensional tiny features, particularly in ultra-hard and exotic materials. The present work investigates the effect of different parameters of the μ-ED milling, such as pulse on time (T
on), pulse off time (T
off), voltage (V), and tool rotation (TR) on the dimensional deviation (DD), material removal rate (MRR), surface roughness (Ra), and machined surface characteristics (analyzed by EDS and FESEM). The sesame oil as dielectric and tungsten-copper as tool electrodes were used to maintain the accuracy and improve the machinability of bio-grade Nitinol shape memory alloy (SMA). Response surface methodology (RSM) and genetic algorithms (GAs) were used to optimize the various input parameters of the μ-ED milling process. Artificial neural network was combined with GA to find the best parametric combination for microchannel fabrication. The cytotoxicity test was also performed on the machined surface to analyze the biocompatibility of the machined surface. It was found that the cell viability of Nitinol SMA was improved by 85.11% after machining at the optimum condition. The highest MRR was found to be 0.076 gm min−1, and the lowest DD and Ra were found to be 16.47 μm and Ra 0.387 μm, respectively.
Reconstruction of local three-dimensional temperature field of tumor cells with low-toxic nanoscale quantum-dot thermometer and cepstrum spatial localization algorithm
Authors: Yang Jun , Huang Lingyu , Du HanLiang , Zhang Lei , Li Ben Q , Xu Mutian
Published: January 2025

The optimal method for three-dimensional thermal imaging within cells involves collecting intracellular temperature responses while simultaneously obtaining corresponding 3D positional information. Current temperature measurement techniques based on the photothermal properties of quantum dots face several limitations, including high cytotoxicity and low fluorescence quantum yields. These issues affect the normal metabolic processes of tumor cells. This study synthesizes a low-toxicity cell membrane-targeted quantum dot temperature sensor by optimizing the synthesis method of CdTe/CdS/ZnS core–shell structured quantum dots. Compared to CdTe-targeted quantum dot temperature sensors, the cytotoxicity of CdTe/CdS/ZnS-targeted quantum dot temperature sensors is reduced by 40.79%. Additionally, a novel cepstrum-based spatial localization algorithm is proposed to achieve rapidly compute the three-dimensional positions of densely distributed quantum dot temperature sensors. Ultimately, both targeted and non-targeted CdTe/CdS/ZnS quantum dot temperature sensors were used simultaneously to label the internal and external regions of human osteosarcoma cells to obtain temperature data at these labeling positions. By combining this with the cepstrum-based spatial localization algorithm, the spatial coordinates of the quantum dot temperature sensors were obtained. Three-dimensional temperature field reconstruction of three local regions was achieved within a 12 μm axial range in living cells. The method described in this paper can be widely applied to the quantitative study of intracellular thermal responses.
Effect of shot peening on microstructural features, residual stress behavior, and hardness of aluminum alloy 2014
Authors: K Venkateswara Reddy , V Rambabu , Mrudula G , Prakash P , Venkatesh Durga Janaki , Mudunuri Rajesh , Satyanarayana M V N V
Published: January 2025

The current study investigates the effect of shot peening on the microstructural features, residual stress distribution, and surface hardness of aluminum alloy 2014, which is essential for applications in aerospace, automobile, and structural components requiring improved fatigue life and wear resistance. Microstructural analysis reveals significant grain refinement (6.6 μm) in the treated specimen and fragmentation of Al2Cu precipitates, reducing their size from 1.9 μm in the untreated specimen to 0.6 μm in the treated specimen. X-ray diffraction confirms grain refinement and increased dislocation density in the shot-peened alloy, evidenced by enhanced peak intensities and slight broadening. Residual stress measurements show a shift from near-neutral stresses in the untreated alloy to compressive stresses in the shot-peened layer, with a peak stress of −313.1 MPa at the surface, transitioning to tensile stresses at deeper layers. Surface hardness analysis shows a substantial increase to 131.5 HV near the surface, compared to 115 HV in the untreated specimen, due to work hardening, grain refinement, and induced compressive stresses.
Trade Agreements and Women
Authors: Bahri Amrita
Published: January 2025

This book explores whether and how trade agreements can enhance women empowerment, how they might be altered to more effectively address such interests, and what different negotiating options countries have for including women’s concerns in their future trade agreements. With a multitude of trade negotiations ongoing and an increasing demand for attention to non-trade issues on the verge of trade cooperation, this book presents a unique tool for trade negotiators and policymakers to address the topic of women empowerment in the trade policy context. It provides timely contributions and guidance for policymakers to prepare, revise, and negotiate new norms to regulate trade in an inclusive manner and to ensure that it works for all including women.
Can Trade Agreements Empower Women?
Authors: Bahri Amrita
Published: January 2025

With the growing proliferation of free trade agreements (FTAs) and the understanding on how FTAs have disproportionately impacted women in their varying roles, the next obvious questions to address are whether and how FTAs can accommodate concerns relating to women and help them address the barriers they face. To address these questions, this chapter provides a discussion on possible positive ways in which trade agreements can impact women, followed by several ways in which trade agreements can negatively impact women. Rooted in several legal, political, economic, and social reasons, it then prepares a case for why trade agreements should be employed to address women’s concerns and what reasons have caused a surge in the number of FTAs being negotiated with women-related provisions. The chapter concludes by providing some reflections on how different regions have treated this subject in their FTAs and the differences and similarities in their respective approaches.
The Pentagon Roadmap for Trade and Gender Negotiations
Authors: Bahri Amrita
Published: January 2025

This chapter proposes a five-dimensional blueprint for women-related provisions with five policy recommendations under each dimension that trade negotiators can consider for future trade negotiations. These recommendations are not ‘one-size-fits-all’ and hence some of the recommendations may work better for some countries than others. Therefore countries should consider these recommendations in light of their own political will, socio-economic needs, existing domestic laws, and available resources. Nevertheless, the policy recommendations attempt to propose a blueprint for how trade negotiations on women-related provisions can be shaped and carried out in the future and how such inclusions can be made more meaningful to ensure that they address the barriers women face.
Capsular Contracture After Breast Augmentation: A Systematic Review and Meta-Analysis
Authors: Haas Evan , Christodoulou Neophytos , Secanho Murilo , Kokosis George , Malgor Rafael D , Winocour Julian , Yu Jason W , Mathes David W , Kaoutzanis Christodoulos
Published: January 2025

Capsular contracture is characterized by the formation of a fibrous capsule around a breast implant after an augmentation mammaplasty, and often results in pain, firmness, and implant distortion. The aim of this meta-analysis was to investigate how implant and surgical characteristics affect rates of capsular contracture after breast augmentation. A systematic review and meta-analysis were performed in PubMed MEDLINE, EMBASE (OvidSP), and Cochrane Library. Comparison groups included smooth vs textured implants; subpectoral vs prepectoral implant placement; saline vs silicone implants. Odds ratios (ORs) were calculated for capsular contracture for each of these groups. The inclusion criteria were met in 24 studies. Smooth implants were associated with significantly higher capsular contracture rates compared with textured implants (OR = 2.80, 95% CI, 1.92-4.08). Subpectoral implant placement demonstrated significantly reduced capsular contracture rates compared with prepectoral placement (OR = 0.35, 95% CI, 0.25-0.50). No significant difference in capsular contracture rates was found between silicone and saline (OR = 0.39, 95% CI, 0.02-6.69). This meta-analysis suggests that textured-surface implants are associated with lower capsular contracture rates than smooth implants following breast augmentation. Additionally, subpectoral implant placement was associated with significantly reduced rates of capsular contracture compared with prepectoral placement. There was no significant difference in capsular contracture rates between saline and silicone implants. However, the absence of large, randomized controlled trials included in this study underscores the need for prospective investigation of the relationship between implant and surgical characteristics and postoperative outcomes.

Level of Evidence: 2 (Risk)
Detection and prognostic relevance of PLA2R epitopes in idiopathic membranous nephropathy: a simultaneous quantitative multiplex suspension array detection method
Authors: Wu Juan , Zhang Qingjuan , Du Yuanyuan , Zheng Tianyu , Jin Juan , Kao Shangbin , Zhou Xiumei , Qin Yuan , Zhao Xueqin , He Qiang , Yang Fuzhou , Huang Biao
Published: January 2025

Objective

This study aimed to develop a multiplex suspension assay for the simultaneous quantitative detection of anti-cysteine-rich domain (anti-CysR)/C-type lectin domain 1 (CTLD1)/C-type lectin domain 6–8 (CTLD678)-IgG4 antibodies of M-type phospholipase A2 receptor (PLA2R) in the serum samples of patients to evaluate the clinical application value of PLA2R epitope spreading in disease prognosis.

Methods

CysR, CTLD1, and CTLD678 antigen domains were coupled to three types of microspheres. The optimal dilution ratio of biotinylated anti-human IgG4 was identified, and a multiplex suspension assay was evaluated in terms of linearity, sensitivity, precision, specificity, and recovery rate. Lastly, the relationship between epitope spreading and the severity of idiopathic membranous nephropathy (IMN) was evaluated.

Results

The content of all three epitopes could be detected simultaneously within two hours. The intra-assay precision ranged from 4.74% to 9.48% , and the inter-assay precision was between 5.13% and 13.92% . Specific experiments showed that the human IgA antibody did not cause a cross-reaction. The recovery rates ranged between 90% and 100%. The cut-off values of epitopes CysR, CTLD1 and CTLD678 between healthy individuals and patients were 6.30, 12.38, and 10.06 Ru/mL, respectively. Among them, the positive rates of epitopes CysR, CTLD1 and CTLD678 were 100%, 34%, and 75%, respectively. In addition, group 3 (CTLD1 response) accounted for 73% of the twelve patients who were not in remission. Meanwhile, When the concentration of CTLD1 exceeds 42.76 Ru/mL, the patient's prognosis may be poorer.

Conclusion

A multiplex suspension assay was developed for the simultaneous quantitative detection of anti-CysR/CTLD1/CTLD678-IgG4 antibodies. The epitope migration sequence of PLA2R molecules during disease progression may not follow a simple linear rule. Among them, the epitope CTLD1 is likely to exert the most significant influence on patient remission.
Intraplate seismicity in southwestern Norway: enhanced catalogue highlights diffusive earthquake occurrence linked to inherited weakness zones
Authors: Marck Angélique , Ottemöller Lars , Rondenay Stéphane , Fossen Haakon
Published: January 2025

Intraplate earthquakes in stable continental regions exhibit diverse characteristics in terms of timing, spatial distribution and magnitude. They are often unexpected, and their underlying physical mechanisms are not well understood. This complexity is particularly apparent in Norway, where seismicity is mostly localized on the continental margin and coastal areas. Various studies have attempted to explain the causes of seismicity in Norway by invoking different sources of stress, ranging from regional stress due to ridge push to local effects such as topography or deglaciation. In this study, we revisit these questions by investigating the distribution of seismicity in southwestern Norway using an enhanced earthquake catalogue. To achieve this, we revised the Norwegian National Seismic Network seismic catalogue from 2000 to 2023 and built a new catalogue using machine-learning-based techniques on data from a temporary seismic deployment in the region. Thanks to the increased station density during this deployment, we were also able to calculate new fault plane solutions that consistently showed a WNW–ESE direction for the most compressive axis. Furthermore, we demonstrate that seismicity in southwestern Norway, while diffuse, tends to be localized around the major crustal shear zones of the region, such as the Bergen Arc Shear Zone and the Hardangerfjord Shear Zone.
Effects of Tesamorelin on Neurocognitive Impairment in Abdominally Obese Persons with HIV
Authors: Ellis Ronald J , Vaida Florin , Hu Keren , Dube Michael , Henry Brook , Chow Felicia , Heaton Robert K , Lee Daniel , Sattler Fred
Published: January 2025

Background

In people with HIV (PWH) who are virally suppressed (VS) on antiretroviral therapy (ART), abdominal obesity (AO) is linked to neurocognitive impairment (NCI), potentially due to visceral adiposity, inflammation, and reduced insulin-like growth factor 1 (IGF-1). Tesamorelin, a growth hormone-releasing hormone, reduces AO and increases IGF-1, suggesting it might mitigate NCI in VS PWH.

Methods

This 6-month, Phase II randomized, open-label clinical trial compared Tesamorelin versus standard-of-care (SOC) for NCI in abdominally obese PWH. Participants had VS, NCI, and AO (elevated waist circumference [WC]). Exclusions included conditions other than HIV causing NCI, active substance use disorder, and malignancy.

Results

Seventy-three participants were randomized 3:2 to Tesamorelin or SOC (2mg subcutaneously daily). The primary outcome was the change in neurocognitive performance at 6 months, with secondary outcomes including WC, mood, and daily functioning. The groups were well-matched at baseline. The Tesamorelin group showed a trend toward improved neurocognitive performance after 6 months (mean change: 0.146, 95% CI: -0.002 to 0.294, p=0.060), while the SOC group did not (0.103, 95% CI: -0.095 to 0.301, p=0.295), but the between-group difference was not significant (p=0.673). IGF-1 levels increased, but changes did not correlate with sRCS or WC. The Tesamorelin group had a greater reduction in WC than the SOC group (median difference -2.7 cm, p=0.015).

Conclusions

While tesamorelin reduced WC, the cognitive benefits did not significantly differ between groups. Recognizing the limitations of insufficient power and no placebo arm, this study suggests no clear benefit of short-term AO reduction with tesamorelin on NCI.
Human HKU1-reactive CD4 T cells are enriched for cytolytic potential that persists in older adults
Authors: White Chantelle L , Richards Katherine A , Huertas Nelson , Nayak Jennifer L , Sant Andrea J
Published: January 2025

The emergence of SARS-CoV-2 increased interest in cellular immunity established by infections with human coronaviruses (HCoVs). Using PBMC from a cohort of human subjects collected prior to 2019, we assessed the abundance and phenotype of these CD4 T cells using cytokine Elispot assays. Unexpectedly, cytotoxic potential was uniquely enriched amongst HKU1-reactive CD4 T cells, as measured by quantification of granzyme producing cells. Also, although dramatic losses in HCoV-specific CD4 T cells abundance for OC43, NL63 and 229E-specific cells were observed in older subjects relative to younger adults, HKU1-reactive cells exhibited minimal age-dependent differences in this phenotype.
Estimating indoor tile friction coefficient using visual information
Authors: Yang Jung-Hwan , Yoon Kang-Il , Ha Seunghyeon , Hong Andy , Lim Soo-Chul
Published: January 2025

Slip and fall accidents are common both indoors and outdoors, posing and risks from minor to serious injuries. An effective way to prevent these accidents is for pedestrians to know the friction properties of their path beforehand. Developing a network that can discern the frictional properties of surfaces from camera-captured images and convey this information to pedestrians could significantly reduce the incidence of slips. However, predicting the indoor friction coefficient of tiles accurately is challenging due to reflections from multiple fluorescent lights and the tiles themselves. Additionally, water accumulation on tiles due to cleaning or leakage greatly contributes to slip accidents. This paper presents an algorithm that accurately predicts floor friction coefficients in real indoor environments, accounting for image distortions caused by light reflections and water on the floor. Experimental results validate that the proposed system reliably predicts indoor floor friction coefficients despite factors such as lighting angles and water presence. Moreover, to demonstrate its practical applicability, a user-application has been developed to predict the friction coefficient for specific areas as required. This system can be integrated into various devices, including walkers, canes, and smartphones, to assist pedestrians in navigating safely.
A multi-threshold image segmentation method based on arithmetic optimization algorithm: A real case with skin cancer dermoscopic images
Authors: Hao Shuhui , Huang Changcheng , Chen Yi , Wang Mingjing , Liu Lei , Xu Suling , Chen Huiling
Published: January 2025

Multi-threshold image segmentation (MTIS) is a crucial technology in image processing, characterized by simplicity and efficiency, and the key lies in the selection of thresholds. However, the method's time complexity will grow exponentially with the number of thresholds. To solve this problem, an improved arithmetic optimization algorithm (ETAOA) is proposed in this paper, an optimizer for optimizing the process of merging appropriate thresholds. Specifically, two optimization strategies are introduced to optimize the optimal threshold process: elite evolutionary strategy (EES) and elite tracking strategy (ETS). First, to verify the optimization performance of ETAOA, mechanism comparison experiments, scalability tests, and comparison experiments with nine state-of-the-art peers are executed based on the benchmark functions of CEC2014 and CEC2022. After that, to demonstrate the feasibility of ETAOA in the segmentation domain, comparison experiments were performed using 10 advanced segmentation methods based on skin cancer dermatoscopy image datasets under low and high thresholds, respectively. The above experimental results show that the proposed ETAOA performs outstanding optimization compared with benchmark functions. Moreover, the experimental results in the segmentation domain show that ETAOA has superior segmentation performance under low and high threshold conditions.
Advances in breeding for enhanced iron and zinc concentrations in common bean in eastern Africa
Authors: Kimani Paul M
Published: January 2025

Micronutrient malnutrition is one of the most serious health challenges facing vast sectors of the population of Africa, particularly resource-poor women and children. The main deficiencies include iron (Fe), zinc (Zn), and vitamin A. Plant breeding has frequently been advocated as the most sustainable strategy to provide varieties of different food crop species with enhanced micronutrient density to combat the global hidden hunger problem which affects >2 billion people. However, there are few research programmes which have implemented this approach, from concept stage to finished products, which can be widely disseminated and commercialized to create meaningful impact. The east African bean biofortification programme offers a case study of such a programme. The aim of this programme was to develop well-adapted, high-yielding, Fe- and Zn-rich bush and climbing bean cultivars and agronomic approaches that enhance expression of the high mineral trait. The objective of this review is to provide a synthesis of the progress made in the last 22 years, with a focus on genetic diversity, inheritance, bioavailability of Fe and Zn, and cooking quality, as well as to identify research gaps and suggest future directions.
Mechanistic determinants and dynamics of cA6 synthesis in type III CRISPR-Cas effector complexes
Authors: Jungfer Kenny , Moravčík Štefan , Garcia-Doval Carmela , Knörlein Anna , Hall Jonathan , Jinek Martin
Published: January 2025

Type III clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems (type III CRISPR-Cas systems) use guide RNAs to recognize RNA transcripts of foreign genetic elements, which triggers the generation of cyclic oligoadenylate (cOA) second messengers by the Cas10 subunit of the type III effector complex. In turn, cOAs bind and activate ancillary effector proteins to reinforce the host immune response. Type III systems utilize distinct cOAs, including cyclic tri- (cA3), tetra- (cA4) and hexa-adenylates (cA6). However, the molecular mechanisms dictating cOA product identity are poorly understood. Here we used cryoelectron microscopy to visualize the mechanism of cA6 biosynthesis by the Csm effector complex from Enterococcus italicus (EiCsm). We show that EiCsm synthesizes oligoadenylate nucleotides in 3′–5′ direction using a set of conserved binding sites in the Cas10 Palm domains to determine the size of the nascent oligoadenylate chain. Our data also reveal that conformational dynamics induced by target RNA binding results in allosteric activation of Cas10 to trigger oligoadenylate synthesis. Mutations of a key structural element in Cas10 perturb cOA synthesis to favor cA3 and cA4 formation. Together, these results provide comprehensive insights into the dynamics of cOA synthesis in type III CRISPR-Cas systems and reveal key determinants of second messenger product selectivity, thereby illuminating potential avenues for their engineering.
Cryo-EM structure of human TUT1:U6 snRNA complex
Authors: Yamashita Seisuke , Tomita Kozo
Published: January 2025

U6 snRNA (small nuclear ribonucleic acid) is a ribozyme that catalyzes pre-messenger RNA (pre-mRNA) splicing and undergoes epitranscriptomic modifications. After transcription, the 3′-end of U6 snRNA is oligo-uridylylated by the multi-domain terminal uridylyltransferase (TUTase), TUT1. The 3′- oligo-uridylylated tail of U6 snRNA is crucial for U4/U6 di-snRNP (small nuclear ribonucleoprotein) formation and pre-mRNA splicing. Here, we present the cryo-electron microscopy structure of the human TUT1:U6 snRNA complex. The AUA-rich motif between the 5′-short stem-loop and the telestem of U6 snRNA is clamped by the N-terminal zinc finger (ZF)–RNA recognition motif and the catalytic Palm of TUT1, and the telestem is gripped by the N-terminal ZF and the Fingers, positioning the 3′-end of the telestem in the catalytic pocket. The internal stem-loop in the 3′-stem-loop of U6 snRNA is anchored by the C-terminal kinase-associated 1 domain, preventing U6 snRNA from dislodging on the TUT1 surface during oligo-uridylylation. TUT1 recognizes the sequence and structural features of U6 snRNA, and holds the entire U6 snRNA body using multiple domains to ensure oligo-uridylylation. This highlights the specificity of TUT1 as a U6 snRNA-targeting TUTase.
A trigger-inducible split-Csy4 architecture for programmable RNA modulation
Authors: Zhang Lihang , Qiu Xinyuan , Zhou Yuting , Luo Zhengyang , Zhu Lingyun , Shao Jiawei , Xie Mingqi , Wang Hui
Published: January 2025

The CRISPR-derived endoribonuclease Csy4 is a popular tool for controlling transgene expression in various therapeutically relevant settings, but adverse effects potentially arising from non-specific RNA cleavage remains largely unexplored. Here, we report a split-Csy4 architecture that was carefully optimized for in vivo usage. First, we separated Csy4 into two independent protein moieties whose full catalytic activity can be restored via various constitutive or conditional protein dimerization systems. Next, we show that introduction of split-Csy4 into human cells caused a substantially reduced extent in perturbation of the endogenous transcriptome when directly compared to full-length Csy4. Inspired by these results, we went on to use such split-Csy4 module to engineer inducible CRISPR- and translation-level gene switches regulated by the FDA-approved drug grazoprevir. This work provides valuable resource for Csy4-related biomedical research and discusses important issues for the development of clinically eligible regulation tools.
Therapeutic manipulation and bypass of the blood–brain barrier: powerful tools in glioma treatment
Authors: Giantini-Larsen Alexandra M , Pandey Abhinav , Garton Andrew L A , Rampichini Margherita , Winston Graham , Goldberg Jacob L , Magge Rajiv , Stieg Philip E , Souweidane Mark M , Ramakrishna Rohan
Published: January 2025

The blood–brain barrier (BBB) remains an obstacle for delivery of chemotherapeutic agents to gliomas. High grade and recurrent gliomas continue to portend a poor prognosis. Multiple methods of bypassing or manipulating the BBB have been explored, including hyperosmolar therapy, convection-enhanced delivery (CED), laser-guided interstitial thermal therapy (LITT), and Magnetic Resonance Guided Focused Ultrasound (MRgFUS) to enhance delivery of chemotherapeutic agents to glial neoplasms. Here, we review these techniques, currently ongoing clinical trials to disrupt or bypass the BBB in gliomas, and the results of completed trials.
Dumbbell-shaped thrombectomy device for cerebral venous sinus thrombus removal with controllable axial and longitudinal maneuverability
Authors: Li Ming , Song Baoying , Wu Yan , Zhang Yang , Cao Xiaofeng , Zhang Hongkang , Xu Yi , Wu Chuanjie , Li Chuanhui , Zhou Chen , Liu Lu , Yan Feng , Li Sijie , Chen Jian , Meng Ran , Duan Jiangang , Wu Di , Zuo Lin , Xu Zikai , Li Zhou , Zheng Yufeng , Jiang Miaowen , Ji Xunming
Published: January 2025

Cerebral venous sinus thrombosis (CVST) is frequently observed in younger adults and features in large thrombus volume. Due to the triangular-like cross-sectional shape and large diameter of the superior sagittal sinus, all the commercially available artery stent retrievers are not suitable for venous vessels. In this study, a dumbbell-like stent was designed and fabricated by 3D braided technology using NiTi wires; it was manually rotatable and stretchable with controlled length/diameter ratios (2.6–14.0) and reciprocating maneuverability. Computational modeling and an in vitro study were conducted to evaluate the mechanical properties of this device and its ability to trap and remove thrombi from occluded venous vessels was verified by using a swine model. A single-center retrospective clinical study of 10 patients using the Venus-TD to treat patients with CVST was also conducted. Pre/postoperative thrombus volume in 10 patients was quantitatively analysed (12 855.3 ± 6417.1 vs. 2373.1 ± 2759.0 mm³, P < 0.001) with a high recanalization rate, yielding favorable clinical outcomes. This study offers a novel treatment option for patients with extensive CVST.
A Quantitative Polymerase Chain Reaction (qPCR) Protocol Predictive of Treatment Outcome in Cutaneous Leishmaniasis Caused by Leishmania braziliensis
Authors: Lordêlo Bianca , Magalhães Andréa , Noronha Almério , Oliveira Livia , Beiting Daniel , Scott Phillip , Carvalho Edgar M , Carvalho Lucas P
Published: January 2025

Leishmania braziliensis is the most prevalent agent causing cutaneous leishmaniasis (CL) in Brazil. While inflammation is a hallmark of CL, few parasites are found at the lesion site, leading to challenges regarding diagnosis. Using L braziliensis kDNA and human 18S rRNA as targets, the present study developed a quantitative polymerase chain reaction assay to determine parasite load in biopsies from patients with CL who were residing in an endemic area in northeastern Brazil. In addition, we investigated whether parasite load correlated with clinical outcome, and we observed that patients with higher parasite load were more likely to experience therapy failure. Moreover, patients with CL in the early phase of infection presented higher levels of parasite transcripts than individuals in later phases. Thus, our results suggest that parasite load as determined by quantitative polymerase chain reaction may constitute a valuable prognostic tool to aid in the determination of disease severity and treatment outcome.
The Icarian flight of antibody-drug conjugates: target selection amidst complexity and tackling adverse impacts
Authors: Liu Han , Zeng Hongye , Qin Xiaojing , Ning Wenjing , Xu Lin , Yang Shiting , Liu Xue , Luo Wenxin , Xia Ningshao
Published: January 2025

Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
High-zinc rice and randomized nutrition training among women farmers: a panel data analysis of long-term adoption in Bangladesh
Authors: Valera Harold Glenn A , Antonio Ronald Jeremy , Habib Muhammad Ashraful , Puskur Ranjitha , Pede Valerien , Yamano Takashi
Published: January 2025

This paper aims to examine the effect of nutrition training on the adoption of high-zinc rice among female farmers with young children in Bangladesh. The authors first conducted a randomized controlled trial by providing female farmers with micronutrient training in randomly selected villages in May–June 2017, followed by a phone-based survey on high-zinc rice seeds among farmer trainees and counterparts in control villages. We conducted a three-visit panel survey in 2018–20 to measure the effect of nutrition training on high-zinc rice adoption. We found that the adoption of high-zinc rice in the Aman or rainy season during July–August declined from 59 per cent in 2018 to 8 per cent in 2020 among treated farmers and from 13 per cent to 2 per cent among control farmers. The regression analysis indicated that nutrition training had a significant but diminishing effect on the adoption of high-zinc rice. Unavailability of seeds and low yields were cited as the major reasons for not using high-zinc rice, while lack of knowledge about high-zinc rice was the dominant reason among the control farmers. The results have shown that continuous training, public messaging, and improving seed systems are required to sustain zinc rice adoption. The trainings should tackle the nutritional advantages of biofortified crops to ensure knowledge retention and farm practices and management techniques to achieve optimal production.
Impact of bladder management methods and other factors on sexual activity in women with chronic spinal cord injury/disease
Authors: Mahler Jasmin Lea , Schneider Salome , Wöllner Jens , Pannek Jürgen , Krebs Jörg
Published: January 2025

Background

Spinal cord injury/disease (SCI/D) profoundly affects both sexuality and urinary function. Catheterization is often necessary to manage bladder voiding and it can interfere with sexual activity.

Aim

We aim to investigate the effect of the bladder evacuation method on sexual activity in women with chronic SCI/D.

Methods

This cross-sectional study at a specialized SCI/D rehabilitation center recruited women ≥18 years with chronic SCI/D using intermittent or suprapubic catheterization. We assessed sexual activity and sexual function with the German version of the Sexual Behaviour Questionnaire and the Female Sexual Function Index (FSFI) and a study-specific questionnaire.

Outcomes

The primary outcome was sexual activity and secondary outcomes included factors influencing sexual activity, such as age and SCI/D characteristics.

Results

Around half of the evaluated women were sexually active, regardless of bladder evacuation method. However, significantly (P = .018) more women using intermittent catheterization (IC) (66.7%, 20/30) were sexually active compared to those with a suprapubic catheter (SPC) (29.4%, 5/17). The main concern for women using IC was urinary incontinence during sex (43.3%, 13/30), while those with a SPC struggled with self-image due to the catheter (58.8%, 10/17). Not having a partner was the most common reason for sexual inactivity in both groups (59.1%). The median FSFI total score was significantly (P = .049) greater in the IC group (median 26.4, lower quartiles [LQ] 8.9/upper quartiles [UQ] 28.8) compared to the SPC group (median 11.5, LQ 5.4/UQ 25.5), which represents a lower grade of sexual dysfunction in women using IC.

Clinical Translation

Sexual education is crucial and should be adapted to the different types of bladder management.

Strength & Limitations

This study shows first data on the effect of catheter on sexual activity in women. Limitation of our study is the small sample size and response bias by the high rejection rate of women with SPC.

Conclusions

Few women with SPC remain sexually active after SCI/D, while the majority of women using IC do, highlighting issues around self-image and urinary incontinence.
Can erector spinae plane block replace intrathecal morphine in cesarean section? A prospective randomized controlled study on opioid consumption
Authors: Sirin Betul Yusra , Teomete Gulsen , Bilgili Beliz
Published: January 2025

Objectives:

After cesarean, optimal analgesia is important for early mobilization, mitigating thromboembolic risks, and mother-infant communication. Our study aims to compare the postoperative analgesic effects of intrathecal morphine (ITM) and Erector Spinae Plane Block (ESPB) in elective cesarean section under spinal anesthesia.

Methods:

82 patients were randomized into ESPB and ITM groups. Both groups received spinal anesthesia with 10 mg of heavy bupivacaine. In the ITM group, intrathecal morphine (100 mcg) was added. The ESPB group received bilateral T10 level ESPB with 20 ml 0.25% bupivacaine postoperatively. Postoperative pain control included intravenous paracetamol 4x1gr, intravenous patient-controlled analgesia with tramadol, and diclofenac 75 mg for rescue analgesia when NRS > 4. NRS, tramadol consumption, and side effects were recorded 24 hours postoperatively. The primary outcome of this study is to compare 24-hour postoperative opioid consumption after cesarean sections. Secondary outcomes include postoperative pain scores, rescue analgesia needs, and potential side effects.

Results:

NRS scores ≤ 4 at all time intervals and were comparable among groups. The total 24-hour tramadol consumption was significantly higher in ESPB group (median: 75; Q1,Q3[40,140]) compared to ITM (50 [27.5,60], P = 0.008). Tramadol consumption was similar among groups during 0-6 and 6-12 hours. In the 12-24 hours, it was significantly higher in ESPB group (22.5 [15,57.5]) compared to ITM (15 [12.5,25],P = 0.005). In ITM group, nausea and vomiting were observed in 3 patients, itching in 1 patient; no adverse effects were observed in ESPB group.

Discussion:

Patients undergoing cesarean section under spinal anesthesia, intrathecal morphine reduced opioid consumption more effectively than ESPB. ESPB is not recommended as a primary analgesic option for cesarean sections.