Prediction of stability coefficient of open-pit mine slope based on artificial intelligence deep learning algorithm

Abstract: Abstract The mining of open pit mines is widespread in China, and there are many cases of landslide accidents. Therefore, the problem of slope stability is highlighted. The stability of the slope is a factor that directly affects the mining efficiency and the safety of the entire mining process. According to the statistics, there is a 15 percent chance of finding landslide risk in China’s large-scale mines. And due to the expansion of the mining scale of the enterprise, the problem of slope stability has become increasingly obvious, which has become a major subject in the study of open-pit mine engineering. In order to better predict the slope stability coefficient, this study takes a mine in China as a case to deeply discuss the accuracy of different algorithms in the stability calculation, and then uses a deep learning algorithm to study the stability under rainfall conditions. The change of the coefficient and the change of the stability coefficient before and after the slope treatment are experimentally studied with the displacement of the monitoring point. The result shows that the safety coefficient calculated by the algorithm in this paper is about 7% lower than that of the traditional algorithm. In the slope stability analysis before treatment, the safety factor calculated by the algorithm in this paper is 1.086, and the algorithm in this paper is closer to reality. In the stability analysis of the slope after treatment, the safety factor calculated by the algorithm in this paper is 1.227, and the stability factor meets the requirements of the specification. It also shows that the deep learning algorithm effectively improves the efficiency of the slope stability factor prediction and improves security during project development.


Cracking rare disorders: a new minimally invasive RNA-seq protocol

Abstract: Abstract RNA sequencing (RNA-seq) has become key to complementing exome and genome sequencing for variant interpretation. We present a minimally invasive RNA-seq protocol using short-term cultured peripheral blood mononuclear cells (PBMCs) with and without cycloheximide treatment, enabling detection of transcripts subject to nonsense-mediated decay. While broadly applicable, this protocol is particularly suited for neurodevelopmental disorders, as up to 80% of the genes in our intellectual disability and epilepsy gene panel are expressed in PBMCs. Applied to 46 affected individuals and 15 parents, RNA-seq revealed splicing defects in six of nine individuals with splice variants, allowing reclassification of seven variants. Targeted cDNA analysis confirmed aberrant splicing in four individuals but missed intron retention in two. Global analyses (FRASER, OUTRIDER, and monoallelic expression) supported findings but did not yield new diagnoses. We propose a flowchart integrating RNA-seq into diagnostic workflows. Overall, our protocol is easily implementable, captures complex splicing events, and enhances variant classification.

Laurenz De Cock
Erika D’haenens
Lies Vantomme
Lynn Backers
Aude Beyens
Kathleen BM Claes
Griet De Clercq
Robin de Putter
Candy Kumps
Nika Schuermans
Jo Sourbron
Hannes Syryn
Simon Tavernier
Eva Vanbelleghem
Olivier Vanakker
Bart Vandekerckhove
Tim Van Damme
Bert Callewaert
Annelies Dheedene
Sarah Vergult
Björn Menten


Vehicular ad hoc networks verification scheme based on bilinear pairings and networks reverse fuzzy extraction

Abstract: Abstract Vehicular Ad-Hoc Networks (VANETs) have facilitated the massive exchange of real-time traffic and weather conditions, which have helped prevent collisions, reduce accidents, and road congestions. This can effectively enhance driving safety and efficiency in technology-driven transportation systems. However, the transmission of massive and sensitive information across public wireless communication channels exposes the transmitted data to a myriad of privacy as well as security threats. Although past researches has developed many vehicular ad-hoc networks security preservation schemes, several of them are inefficient or susceptible to attacks. This work, introduces an approach that leverages reverse fuzzy extraction, bilinear pairing, and Physically Unclonable Function (PUF) to design an efficient and anonymity-preserving authentication scheme. We conduct an elaborate formal security analysis to demonstrate that the derived session key is secure. The semantic security analyses also demonstrate its resilience against typical VANET attacks such as impersonations, denial of service, and de-synchronization, instilling confidence in its effectiveness. Moreover, our approach incurs the lowest computational overheads at relatively low communication costs. Specifically, our protocol attains a 66.696% reduction in computation costs, and a 70% increment in the supported security functionalities.

Zaid Ameen Abduljabbar
Vincent Omollo Nyangaresi
Ahmed Ali Ahmed
Junchao Ma
Mustafa A. Al Sibahee
Mohammed Abdulridha Hussain
Zaid Alaa Hussien
Ali Hasan Ali
Abdulla J. Y. Aldarwish
Husam A. Neamah


Pt and CoB trilayer Josephson $$\pi $$ π junctions with perpendicular magnetic anisotropy

Abstract: Abstract We report on the electrical transport properties of Nb based Josephson junctions with Pt/Co $$_{68}$$ 68 B $$_{32}$$ 32 /Pt ferromagnetic barriers. The barriers exhibit perpendicular magnetic anisotropy, which has the main advantage for potential applications over magnetisation in-plane systems of not affecting the Fraunhofer response of the junction. In addition, we report that there is no magnetic dead layer at the Pt/Co $$_{68}$$ 68 B $$_{32}$$ 32 interfaces, allowing us to study barriers with ultra-thin Co $$_{68}$$ 68 B $$_{32}$$ 32 . In the junctions, we observe that the magnitude of the critical current oscillates with increasing thickness of the Co $$_{68}$$ 68 B $$_{32}$$ 32 strong ferromagnetic alloy layer. The oscillations are attributed to the ground state phase difference across the junctions being modified from zero to $$\pi $$ π . The multiple oscillations in the thickness range $$0.2~\leqslant ~d_\text {CoB}~\leqslant ~1.4$$ 0.2 ⩽ d CoB ⩽ 1.4  nm suggests that we have access to the first zero- $$\pi $$ π and $$\pi $$ π -zero phase transitions. Our results fuel the development of low-temperature memory devices based on ferromagnetic Josephson junctions.

N. Satchell
T. Mitchell
P. M. Shepley
E. Darwin
B. J. Hickey
G. Burnell


The microwave-absorption properties and mechanism of phenyl silicone rubber/CIPs/graphene composites after thermal-aging in an elevated temperature

Abstract: Abstract Recently, the application and development of flexible microwave-absorption composites based on silicone rubber have gradually become a research hot spot. In this study, methyl vinyl phenyl silicone rubber (MPVQ)/carbonyl iron particles (CIPs)/graphene (GR) composites were prepared by mechanical blending, and the effects of thermal-ageing temperature on the microwave-absorption properties of the composites were investigated. The mechanism of the thermal-ageing temperature’s effects on microwave-absorption behaviour was identified. The results show that unaged composites have superior microwave-absorption properties, with a minimum reflection loss (RL min ) of − 87.73 dB, a lowest thickness of 1.46 mm, and an effective absorption bandwidth (EAB, RL < − 10 dB) reaching 5.8 GHz (9.9–15.7 GHz). With ageing at 240 °C for 24 h, the RL min at a frequency of 5.48 GHz is − 45.55 dB with a thickness of 2.55 mm, and the EAB value reaches 2 GHz (range 4.6–6.6 GHz). In the thermal-ageing process, a crosslinking reaction occurs in MPVQ with an increase in crosslinking density from 5.88 × 10−5 mol g−1 (unaged) to 4.69 × 10−4 mol g−1 (aged at 240 °C). Simultaneously, thermal degradation of the composites leads to a reduction in the rubber concentration. In addition, a small amount of CIPs are oxidized to Fe3O4, and the remaining CIPs aggregate to generate more electrically conductive pathways. Consequently, the dielectric loss of the composites will be significantly improved, resulting in poor impedance matching. The microwave-absorption properties of the composites gradually decrease with increasing thermal-ageing temperature from 200 to 240 °C.


Resting-state EEG measures cognitive impairment in Parkinson’s disease

Abstract: Abstract Cognitive dysfunction is common in Parkinson’s disease (PD). We developed and evaluated an EEG-based biomarker to index cognitive functions in PD from a few minutes of resting-state EEG. We hypothesized that synchronous changes in EEG across the power spectrum can measure cognition. We optimized a data-driven algorithm to efficiently capture these changes and index cognitive function in 100 PD and 49 control participants. We compared our EEG-based cognitive index with the Montreal cognitive assessment (MoCA) and cognitive tests across different domains from National Institutes of Health (NIH) Toolbox using cross-validations, regression models, and randomization tests. Finally, we externally validated our approach on 32 PD participants. We observed cognition-related changes in EEG over multiple spectral rhythms. Utilizing only 8 best-performing electrodes, our proposed index strongly correlated with cognition (MoCA: rho = 0.68, p value < 0.001; NIH-Toolbox cognitive tests: rho ≥ 0.56, p value < 0.001) outperforming traditional spectral markers (rho = −0.30–0.37). The index showed a strong fit in regression models (R 2 = 0.46) with MoCA, yielded 80% accuracy in detecting cognitive impairment, and was effective in both PD and control participants. Notably, our approach was equally effective (rho = 0.68, p value < 0.001; MoCA) in out-of-sample testing. In summary, we introduced a computationally efficient data-driven approach for cross-domain cognition indexing using fewer than 10 EEG electrodes, potentially compatible with dynamic therapies like closed-loop neurostimulation. These results will inform next-generation neurophysiological biomarkers for monitoring cognition in PD and other neurological diseases.

Md Fahim Anjum
Arturo I. Espinoza
Rachel C. Cole
Arun Singh
Patrick May
Ergun Y. Uc
Soura Dasgupta
Nandakumar S. Narayanan

Neurology. Diseases of the nervous system


Development, modelling and optimization of process parameters on the tensile strength of aluminum, reinforced with pumice and carbonated coal hybrid composites for brake disc application

Abstract: Abstract This study focuses on optimizing double stir casting process parameters to enhance the tensile strength of hybrid composites comprising aluminum alloy, brown pumice, and coal ash, intended for brake disc applications. Analytical techniques including X-ray fluorescence, X-ray diffraction, thermogravimetric analysis, and scanning electron microscopy were employed to characterize the composite constituents. The Taguchi method was utilized for experimental design and optimization to determine the optimal weight compositions of brown pumice and coal ash, as well as stir casting parameters (stirrer speed, pouring temperature, and stirring duration). Regression analysis was employed to develop a predictive mathematical model for the tensile strength of the hybrid composites and to assess the significance of process parameters. The optimized composite achieved a predicted tensile strength of 186.81 MPa and an experimental strength of 190.67 MPa using 7.5 vol% brown pumice, 2.5 vol% coal ash, a pouring temperature of 700 °C, stirrer speed of 500 rpm, and stirring duration of 10 min. This represents a 52.23% improvement over the as-cast aluminum alloy’s tensile strength. Characterization results revealed that brown pumice and coal ash contain robust minerals (SiO2, Fe2O3, Al2O3) suitable for reinforcing metal matrices like aluminum, titanium, and magnesium. Thermogravimetric and differential thermal analyses demonstrated thermal stability up to 614.01 °C for the optimized composite, making it suitable for brake disc applications.

Tanimu Kogi Ibrahim
Danjuma Saleh Yawas
Julius Thaddaeus
Bashar Danasabe
Ibrahim Iliyasu
Adetayo Abdulmumin Adebisi
Talib Onimisi Ahmadu


Real-time holographic camera for obtaining real 3D scene hologram

Abstract: Abstract As a frontier technology, holography has important research values in fields such as bio-micrographic imaging, light field modulation and data storage. However, the real-time acquisition of 3D scenes and high-fidelity reconstruction technology has not yet made a breakthrough, which has seriously hindered the development of holography. Here, a novel holographic camera is proposed to solve the above inherent problems completely. The proposed holographic camera consists of the acquisition end and the calculation end. At the acquisition end of the holographic camera, specially configured liquid materials and liquid lens structure based on voice-coil motor-driving are used to produce the liquid camera, so that the liquid camera can quickly capture the focus stack of the real 3D scene within 15 ms. At the calculation end, a new structured focus stack network (FS-Net) is designed for hologram calculation. After training the FS-Net with the focus stack renderer and learnable Zernike phase, it enables hologram calculation within 13 ms. As the first device to achieve real-time incoherent acquisition and high-fidelity holographic reconstruction of a real 3D scene, our proposed holographic camera breaks technical bottlenecks of difficulty in acquiring the real 3D scene, low quality of the holographic reconstructed image, and incorrect defocus blur. The experimental results demonstrate the effectiveness of our holographic camera in the acquisition of focal plane information and hologram calculation of the real 3D scene. The proposed holographic camera opens up a new way for the application of holography in fields such as 3D display, light field modulation, and 3D measurement.

Zhao-Song Li
Chao Liu
Xiao-Wei Li
Yi Zheng
Qian Huang
Yi-Wei Zheng
Ye-Hao Hou
Chen-Liang Chang
Da-Wei Zhang
Song-Lin Zhuang
Di Wang
Qiong-Hua Wang


Author Correction: GFI1 tethers the NuRD complex to open and transcriptionally active chromatin in myeloid progenitors

Anne Helness
Jennifer Fraszczak
Charles Joly-Beauparlant
Halil Bagci
Christian Trahan
Kaifee Arman
Peiman Shooshtarizadeh
Riyan Chen
Marina Ayoub
Jean-François Côté
Marlene Oeffinger
Arnaud Droit
Tarik Möröy


Author Correction: EU-Trees4F, a dataset on the future distribution of European tree species

Achille Mauri
Marco Girardello
Giovanni Strona
Pieter S. A. Beck
Giovanni Forzieri
Giovanni Caudullo
Federica Manca
Alessandro Cescatti


Thermodynamic fluctuation theorems govern human sensorimotor learning

Abstract: Abstract The application of thermodynamic reasoning in the study of learning systems has a long tradition. Recently, new tools relating perfect thermodynamic adaptation to the adaptation process have been developed. These results, known as fluctuation theorems, have been tested experimentally in several physical scenarios and, moreover, they have been shown to be valid under broad mathematical conditions. Hence, although not experimentally challenged yet, they are presumed to apply to learning systems as well. Here we address this challenge by testing the applicability of fluctuation theorems in learning systems, more specifically, in human sensorimotor learning. In particular, we relate adaptive movement trajectories in a changing visuomotor rotation task to fully adapted steady-state behavior of individual participants. We find that human adaptive behavior in our task is generally consistent with fluctuation theorem predictions and discuss the merits and limitations of the approach.

P. Hack
C. Lindig-Leon
S. Gottwald
D. A. Braun


Deglacial release of petrogenic and permafrost carbon from the Canadian Arctic impacting the carbon cycle

Abstract: Abstract The changes in atmospheric pCO2 provide evidence for the release of large amounts of ancient carbon during the last deglaciation. However, the sources and mechanisms that contributed to this process remain unresolved. Here, we present evidence for substantial ancient terrestrial carbon remobilization in the Canadian Arctic following the Laurentide Ice Sheet retreat. Glacial-retreat-induced physical erosion of bedrock has mobilized petrogenic carbon, as revealed by sedimentary records of radiocarbon dates and thermal maturity of organic carbon from the Canadian Beaufort Sea. Additionally, coastal erosion during the meltwater pulses 1a and 1b has remobilized pre-aged carbon from permafrost. Assuming extensive petrogenic organic carbon oxidation during the glacial retreat, a model-based assessment suggests that the combined processes have contributed 8 ppm to the deglacial CO2 rise. Our findings suggest potentially positive climate feedback of ice-sheet retreat by accelerating terrestrial organic carbon remobilization and subsequent oxidation during the glacial-interglacial transition.

Junjie Wu
Gesine Mollenhauer
Ruediger Stein
Peter Köhler
Jens Hefter
Kirsten Fahl
Hendrik Grotheer
Bingbing Wei
Seung-Il Nam


Towards the technological maturity of membrane distillation: the MD module performance curve

Abstract: Abstract Membrane distillation (MD) is constantly acknowledged in the research literature as a promising technology for the future of desalination, with an increasing number of studies reported year after year. However, real MD applications still lag behind with only a few pilot-plant tests worldwide. The lack of technology transfer from academia to industry is caused by important gaps between its fundamental basis and the process design. Herein, we explore critical disconnections by conducting coupled mass and heat transfer modeling and MD simulations; we use well-known MD mass and heat transfer equations to model and simulate flux over a typical MD membrane for different geometries, areas, and operational conditions in direct contact configuration. From the analysis of the results, we propose research guidelines and process development strategies, and construct an MD module performance curve. From this graph, permeate flow rate, thermal energy consumption and outlet temperatures can be determined for given feed inlet conditions (temperature and concentration). Comprehensive tools such as this MD module curve and good communication between membrane developers and process engineers are required to accelerate the process of bringing the MD technology from a still-emerging status to a maturity level.

Pablo López-Porfiri
Sebastián Ramos-Paredes
Patricio Núñez
Patricia Gorgojo

Water supply for domestic and industrial purposes


Structure and transport mechanism of P5B-ATPases

Abstract: In human cells, P5B‐ATPases execute export of spermine from lysosomes to the cytosol, but the mechanisms of spermine recognition, uptake and transport remain elusive. Here the authors present cryo‐EM structures of a yeast homolog of human ATP13A2‐5, Ypk9, which depict three separate transport cycle intermediates, including spermine‐bound conformations

Ping Li
Kaituo Wang
Nina Salustros
Christina Grønberg
Pontus Gourdon


Comparative genomics and metabolomics analysis of Riemerella anatipestifer strain CH-1 and CH-2

Abstract: Abstract Riemerella anatipestifer is a major pathogenic microorganism in poultry causing serositis with significant mortality. Serotype 1 and 2 were most pathogenic, prevalent, and liable over the world. In this study, the intracellular metabolites in R. anatipestifer strains RA-CH-1 (serotype 1) and RA-CH-2 (serotype 2) were identified by gas chromatography-mass spectrometer (GC–MS). The metabolic profiles were performed using hierarchical clustering and partial least squares discriminant analysis (PLS-DA). The results of hierarchical cluster analysis showed that the amounts of the detected metabolites were more abundant in RA-CH-2. RA-CH-1 and RA-CH-2 were separated by the PLS-DA model. 24 potential biomarkers participated in nine metabolisms were contributed predominantly to the separation. Based on the complete genome sequence database and metabolite data, the first large-scale metabolic models of iJL463 (RA-CH-1) and iDZ470 (RA-CH-2) were reconstructed. In addition, we explained the change of purine metabolism combined with the transcriptome and metabolomics data. The study showed that it is possible to detect and differentiate between these two organisms based on their intracellular metabolites using GC–MS. The present research fills a gap in the metabolomics characteristics of R. anatipestifer.

Jibin Liu
Anchun Cheng
Mingshu Wang
Mafeng Liu
Dekang Zhu
Qiao Yang
Ying Wu
Renyong Jia
Shun Chen
Xinxin Zhao
Shaqiu Zhang
Juan Huang
Xumin Ou
Sai Mao
Qun Gao
Xingjian Wen
Ling Zhang
Yunya Liu
Yanling Yu
Bin Tian
Leichang Pan
Mujeeb Ur Rehman
Xiaoyue Chen


Negative emissions technologies and practices could challenge global resource supply and environmental limits

Abstract: Abstract Meeting climate goals will most likely require large-scale carbon dioxide removal, yet its sustainability implications remain poorly understood. Here, we conduct a prospective life cycle assessment of multiple negative emissions technologies and practices, integrating mineral resource, health, and absolute sustainability indicators to quantify impacts between 2030 and 2050. Our comprehensive analysis reveals previously overlooked bottlenecks: biochar and bioenergy with carbon capture and storage could sharply raise nutrient demand, further compromising food security, while direct air carbon capture and storage and ocean liming could critically exacerbate the mining levels of key mineral resources, despite their lower collateral damage. These findings will help guide the sustainable and safe expansion of the carbon dioxide removal industry by balancing multiple risks, thereby minimizing unintended environmental and resource-related consequences.

Selene Cobo
Ángel Galán-Martín
Gonzalo Guillén-Gosálbez


The requirement of mitochondrial RNA polymerase for non-small cell lung cancer cell growth

Abstract: Abstract POLRMT (RNA polymerase mitochondrial) is responsible for the transcription of mitochondrial genome encoding key components of oxidative phosphorylation. This process is important for cancer cell growth. The current study tested expression and potential functions of POLRMT in non-small cell lung cancer (NSCLC). TCGA cohorts and the results from the local lung cancer tissues showed that POLRMT is overexpressed in human lung cancer tissues. In both primary human NSCLC cells and A549 cells, POLRMT silencing (by targeted lentiviral shRNAs) or knockout (through CRSIPR/Cas9 gene editing method) potently inhibited cell viability, proliferation, migration, and invasion, and induced apoptosis activation. On the contrast, ectopic overexpression of POLRMT using a lentiviral construct accelerated cell proliferation and migration in NSCLC cells. The mtDNA contents, mRNA levels of mitochondrial transcripts, and subunits of respiratory chain complexes, as well as S6 phosphorylation, were decreased in POLRMT-silenced or -knockout NSCLC cells, but increased after ectopic POLRMT overexpression. In vivo, intratumoral injection of POLRMT shRNA adeno-associated virus (AAV) potently inhibited NSCLC xenograft growth in severe combined immune deficiency mice. The mtDNA contents, mRNA levels of mitochondria respiratory chain complex subunits, and S6 phosphorylation were decreased in POLRMT shRNA AAV-injected NSCLC xenograft tissues. These results show that POLRMT is a novel and important oncogene required for NSCLC cell growth in vitro and in vivo.

Tong Zhou
Yong-Hua Sang
Shang Cai
Chun Xu
Min-hua Shi


Simultaneous measurement of energy spectrum and fluence of neutrons using a diamond detector

Abstract: Abstract Due to the excellent radiation hardness and high–temperature endurance, diamond detectors are suitable for intense neutron measurements and promising for neutron diagnostics of scientific fusion devices. In the present work, simultaneous measurement of energy spectrum and fluence of neutrons using a diamond detector was realized for the first time. The absolute response matrix of the diamond detector was simulated based on detailed analysis of the nuclear reactions and the proper selection of nuclear reaction data. Neutron energy spectra as well as neutron fluences for 5.0, 5.5, 8.5, 9.5 and 10.5 MeV neutrons from d–d reaction were measured using the diamond detector based on the absolute response matrix. The measured neutron energy spectra and neutron fluences are reasonable compared with those detected using a EJ-309 liquid scintillator and a 238U fission chamber, respectively, which verifies the reliability of the present work. Furthermore, the energy spectrum and fluence of a 14.2 MeV d–t neutron source were also measured using the diamond detector. The present work demonstrates the ability of simultaneous measurement of energy spectrum and fluence as well as for both d–d and d–t neutrons using a diamond detector, which is of great significance for neutron diagnostics of scientific fusion devices.

Jie Liu
Haoyu Jiang
Zengqi Cui
Yiwei Hu
Haofan Bai
Tieshuan Fan
Jinxiang Chen
Yuan Gao
Xiangjun Yang
Guohui Zhang


Tailoring the active site for the oxygen evolution reaction on a Pt electrode

Abstract: Electrocatalytic oxygen evolution is a key reaction for water splitting, but the detailed atomic structures of single-crystal electrodes under cycling conditions are still not fully understood. Here, the authors study the oxygen evolution activity on Pt(111) during potential cycling and find that the current density reaches a maximum in the third cycle and is nine times higher than that in the initial cycle, owing to a roughened Pt(111) surface and formation of islands and atomic vacancies in the second subsurface Pt layer.

Kazuki Iizuka
Tomoaki Kumeda
Kota Suzuki
Hiroo Tajiri
Osami Sakata
Nagahiro Hoshi
Masashi Nakamura


Endothelial ZEB1 promotes angiogenesis-dependent bone formation and reverses osteoporosis

Abstract: An endothelial cell subtype, expressing endomucin and CD31, has been reported to couple angiogenesis with osteogenesis. Here, the authors show that loss of ZEB1 in these cells epigenetically suppresses Notch signaling, leading to impaired angiogenesis and osteogenesis, and that Zeb1 delivery via liposomes ameliorates bone loss in osteoporotic mice

Rong Fu
Wen-Cong Lv
Ying Xu
Mu-Yun Gong
Xiao-Jie Chen
Nan Jiang
Yan Xu
Qing-Qiang Yao
Lei Di
Tao Lu
Li-Ming Wang
Ran Mo
Zhao-Qiu Wu


Author Correction: Therapeutic benefit of Muse cells in a mouse model of amyotrophic lateral sclerosis

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Toru Yamashita
Yoshihiro Kushida
Shohei Wakao
Koh Tadokoro
Emi Nomura
Yoshio Omote
Mami Takemoto
Nozomi Hishikawa
Yasuyuki Ohta
Mari Dezawa
Koji Abe


Association of baseline electrocardiographic left ventricular hypertrophy with future renal function decline in the general population

Abstract: Abstract Electrocardiographic left ventricular hypertrophy (LVH) could predict adverse renal outcomes in patients with hypertension. This study aimed to investigate the association between electrocardiographic LVH and future decline in renal function in the general population using a dataset of population-based health checkups from 2010 to 2019 including 19,825 participants. Electrocardiographic LVH was defined according to the Minnesota code. Renal function decline was defined as a decrease of ≥ 25% in the estimated glomerular filtration rate from baseline to < 60 mL/min/1.73 m2. Electrocardiographic LVH was found in 1263 participants at the baseline visit. The mean follow-up period was 3.4 ± 1.9 years. The incidence rates of renal function decline were 0.30 and 0.78 per 100 person-years in the non-LVH group and LVH groups, respectively. Electrocardiographic LVH was associated with the risk for renal function decline in the adjusted analysis (hazard ratio 1.69, 95% confidence interval 1.14–2.50, P = 0.009). This association was comparable across subgroups stratified by age, sex, body mass index, diagnosed hypertension, systolic blood pressure, hemoglobin A1c, and urinary protein. This study underscores the usefulness of electrocardiographic LVH to detect high-risk individuals for renal function decline in the setting of health checkups in the general population.

Shota Ikeda
Keisuke Shinohara
Koshiro Tagawa
Takeshi Tohyama
Junji Kishimoto
Masaya Kazurayama
Shinji Tanaka
Masamitsu Yamaizumi
Hirokazu Nagayoshi
Kensuke Toyama
Shouji Matsushima
Hiroyuki Tsutsui
Shintaro Kinugawa


RBM3 promotes neurogenesis in a niche-dependent manner via IMP2-IGF2 signaling pathway after hypoxic-ischemic brain injury

Abstract: Therapeutic hypothermia is a potent tool in the treatment of neonatal hypoxic-ischemic (HI) injury, yet the underlying mechanisms remain unclear. Here, authors demonstrate how the RNA-binding motif protein RBM3, which is induced by mild cooling while global translation rate is slowed down, contributes substantially to neuroregeneration after adult HI injury, specifically in the subventricular zone and subgranular zone.

Xinzhou Zhu
Jingyi Yan
Catherine Bregere
Andrea Zelmer
Tessa Goerne
Josef P. Kapfhammer
Raphael Guzman
Sven Wellmann


Hepcidin deficiency in mice impairs white adipose tissue browning possibly due to a defect in de novo adipogenesis

Abstract: Abstract The role of iron in the two major sites of adaptive thermogenesis, namely the beige inguinal (iWAT) and brown adipose tissues (BAT) has not been fully understood yet. Body iron levels and distribution is controlled by the iron regulatory peptide hepcidin. Here, we explored iron homeostasis and thermogenic activity in brown and beige fat in wild-type and iron loaded Hepcidin KO mice. Hepcidin-deficient mice displayed iron overload in both iWAT and BAT, and preferential accumulation of ferritin in stromal cells compared to mature adipocytes. In contrast to BAT, the iWAT of Hepcidin KO animals featured with defective thermogenesis evidenced by an altered beige signature, including reduced UCP1 levels and decreased mitochondrial respiration. This thermogenic modification appeared cell autonomous and persisted after a 48 h-cold challenge, a potent trigger of thermogenesis, suggesting compromised de novo adipogenesis. Given that WAT browning occurs in both mice and humans, our results provide physiological results to interrogate the thermogenic capacity of patients with iron overload disorders.

Jean-Christophe Deschemin
Céline Ransy
Frédéric Bouillaud
Soonkyu Chung
Bruno Galy
Carole Peyssonnaux
Sophie Vaulont


Improved railway track faults detection using Mel-frequency cepstral coefficient and constant-Q transform features

Abstract: Abstract Regular inspection of the health of railway tracks is crucial to maintaining reliable and safe train operations. Some factors including cracks, rail discontinuity, ballast issues, burn wheels, super-elevation, loose nuts and bolts, and misalignment developed on the railways due to pre-emptive investigations, non-maintenance, and delay in detection pose grave threats and danger to the safe operation of railway transportation. In the past, manual inspection was performed for the rail track by a rail cart which is both prone to error and inefficient due to human biases and error. Several train accidents are reported in Pakistan; it is important to automate these techniques to avoid such train accidents for the safety of countless lives. This study aims to enhance railway track fault detection using an automatic rail track fault detection technique with acoustic analysis. Moreover, the proposed method contributes to making the dataset large by using the CTGAN technique. Results show that acoustic data may help to determine the railway track faults effectively and logistic regression is used to perform the classification for railway track faults with an accuracy of 100%.

Rahman Shafique
Khadija Kanwal
Venkata Chunduri
Gyu Sang Choi
Imran Ashraf


Real-world analysis of safety, tolerability, and adherence to nirmatrelvir-ritonavir (paxlovid) in primary care COVID-19 outpatients

Abstract: Abstract This retrospective cross-sectional study aims to evaluate the safety, tolerability, and adherence of patients prescribed Nirmatrelvir-ritonavir (Paxlovid) in outpatient settings, focusing on its use in managing category 2 COVID-19 patients across three primary healthcare clinics in Selangor, Malaysia. Data were collected from the Paxlovid pharmacy registry and medical records at Klinik Kesihatan Seksyen 7, Klinik Kesihatan Seksyen 19, and Klinik Kesihatan Kelana Jaya between April 1, 2022, and November 30, 2022. This study analysed data from 415 category 2 COVID-19 patients aged ≥ 18 years. The primary and secondary outcomes included the assessment of patient demographics, Paxlovid dosing, current medication, changes in drug regimen, adherence, and adverse drug reactions (ADR). Pharmacists follow-ups were conducted on days 3 and 5 post-medication initiation. The majority (79.5%) of the cohort experienced ADR, predominantly dysgeusia, diarrhoea, body ache, vomiting, and nausea. Despite this, the ADRs were generally well-tolerated, with no severe impacts reported. High adherence was observed, with 96.9% of patients completing the 5-day regimen. The primary reasons for non-adherence included adverse effect intolerability, dosing ambiguity, forgetfulness, concerns about ADR, and perceived health improvement. Notable medications interacting with Paxlovid were simvastatin, amlodipine, and atorvastatin, and 21.7% of 23 concurrent medications were found not to comply with the recommended interventions by the University of Liverpool COVID-19 Drug Interaction database. Paxlovid demonstrates a high level of safety and tolerability in outpatient COVID-19 patients, with optimal adherence observed. This study underscores the vital role of healthcare professionals in managing Paxlovid within primary healthcare and highlights the need for broader research and direct patient involvement to enhance treatment strategies against COVID-19.

Zahirah Zaharuddin
Nur Sabiha Md Hussin
Mahmathi Karuppannan


The AST/ALT ratio as a mediator of heavy metal exposure and diabetic kidney disease (DKD) risk: A NHANES study

Abstract: Abstract The potential impact of heavy metal exposure on the progression of diabetic kidney disease (DKD) remains a subject of scientific inquiry. While some studies have hinted at a correlation, definitive evidence is still lacking. It is important to note that certain links, such as the association between cadmium exposure and chronic kidney disease, have been established in prior research. This study seeks to examine the potential link between heavy metal exposure and the risk of DKD. This cross-sectional study included adult type 2 diabetes mellitus (T2DM) patients from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018. The study analyzed nine types of urinary heavy metals and three types of blood heavy metals. Survey-weighted logistic regression, restricted cubic spline (RCS) analysis, weighted quantile sum regression (WQS) regression, and Bayesian kernel machine regression (BKMR) model were employed to evaluate the effects of single and mixed heavy metal exposure on DKD. Subgroup analyses were conducted based on age and gender. Mediation analysis was used to assess the mediating effect of the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio. Additionally, a series of sensitivity analyses were performed. The final analysis included 5,124 individuals (2011–2018), of whom 896 (17.49%) were classified as having DKD. Weighted logistic regression indicated that urinary barium (UBa), urinary cobalt (UCo), urinary cesium (UCs), urinary thallium (UTl), blood cadmium (BCd), and blood lead (BPb) were associated with DKD. RCS analysis indicated a nonlinear relationship between UBa, UCo, UCs, UTl, BPb, and DKD. Both WQS regression and BKMR model consistently demonstrated a negative correlation between urinary mixed heavy metal exposure and the risk of DKD, while blood mixed heavy metal exposure was positively correlated with the risk of DKD, identifying UBa as the primary protective contributor and BCd as the primary risk contributor. Subgroup analysis revealed that age and gender could modify the association between heavy metal exposure and the risk of DKD. Finally, mediation analysis revealed that the AST/ALT ratio played a crucial potential mediating role in the association between heavy metal exposure and the prevalence of DKD. Our findings offer a comprehensive perspective on the relationship between heavy metals (particularly protective UBa and risk-associated BCd) and DKD risk, which holds significant implications for environmental control and early prevention of DKD, it is important to note that our cross-sectional design precludes causal inferences. Future longitudinal studies are needed to establish causality and inform intervention strategies.

Yu Li
Juan Chai
Jinjuan Chen
Jiayin Du
Jianbo Mu
Lingqin Zhang


Therapeutic potential of hyaluronic acid hydrogel combined with bone marrow stem cells-conditioned medium on arthritic rats’ TMJs

Abstract: Abstract Conditioned media (CM) is derived from mesenchymal stem cells (MSC) culture and contains biologically active components. CM is easy to handle and reduces inflammation while repairing injured joints. Combination therapy of the CM with cross-linked hyaluronic acid (HA) could ameliorate the beneficial effect of HA in treating degenerative changes of articulating surfaces associated with arthritic rats’ temporomandibular joints (TMJs). This study aimed to evaluate the therapeutic potential of HA hydrogel combined with bone marrow stem cells-conditioned medium (BMSCs-CM) on the articulating surfaces of TMJs associated with complete Freund’s adjuvant (CFA)-induced arthritis. Fifty female Sprague-Dawley rats were divided randomly into five equal groups. Rats of group I served as the negative controls and received intra-articular (IA) injections of 50 µl saline solution, whereas rats of group II were subjected to twice IA injections of 50 µg CFA in 50 µl; on day 1 of the experiment to induce persistent inflammation and on day 14 to induce arthritis. Rats of group III and IV were handled as group II and instead, they received an IA injection of 50 µl HA hydrogel and 50 µl of BMSCs-CM, respectively. Rats of group V were given combined IA injections of 50 µl HA hydrogel and BMSCs-CM. All rats were euthanized after the 4th week of inducing arthritis. The joints were processed for sectioning and histological staining using hematoxylin and eosin, Masson’s trichrome and toluidine blue special staining, and immunohistochemical staining for nuclear factor-kappa B (NF-κB). SPSS software was used to analyze the data and one-way analysis of variance followed by post-hoc Tukey statistical tests were used to test the statistical significance at 0.05 for alpha and 0.2 for beta. In the pooled BMSC-CM, 197.14 pg/ml of platelet-derived growth factor and 112.22 pg/ml of interleukin-10 were detected. Compared to TMJs of groups III and IV, TMJs of group V showed significant improvements (P = 0.001) in all parameters tested as the disc thickness was decreased (331.79 ± 0.73), the fibrocartilaginous layer was broadened (0.96 ± 0.04), and the amount of the trabecular bone was distinctive (19.35 ± 1.07). The mean values for the collagen amount were increased (12.29 ± 1.38) whereas the mean values for the NF-κB expression were decreased (0.62 ± 0.15). Combination therapy of HA hydrogel and BMSCs-CM is better than using HA hydrogel or BMSCs-CM, separately to repair degenerative changes in rats’ TMJs associated with CFA-induced arthritis.

Mai M. Assi
Mohammed E. Grawish
Heba Mahmoud Elsabaa
Mohamad E. Helal
Samah K. Ezzat


Reinforcement learning with learned gadgets to tackle hard quantum problems on real hardware

Abstract: Abstract Quantum computing offers exciting opportunities for simulating complex quantum systems and optimizing large-scale combinatorial problems, but its practical use is limited by device noise and constrained connectivity. Designing quantum circuits, which are fundamental to quantum algorithms, is therefore a central challenge in current quantum hardware. Existing reinforcement learning-based methods for circuit design lose accuracy when restricted to hardware-native gates and device-level compilation. Here, we introduce gadget reinforcement learning (GRL) that combines learning with program synthesis to automatically construct composite gates that expand the action space while respecting hardware constraints. We show that this approach improves accuracy, hardware compatibility, and scalability for transverse-field Ising and quantum chemistry problems, reaching systems of up to ten qubits within realistic computational budgets. This framework demonstrates how learned, reusable circuit building blocks can guide the co-design of algorithms and hardware for quantum processors.


Unraveling genetic diversity in ‘Foşa’ and ‘Yomra’ hazelnut accessions (Corylus avellana L.) using SSR markers and phenotypic analysis

Abstract: Abstract The Foşa hazelnut variety is commonly cultivated in Türkiye and is often confused with the Yomra variety due to morphological similarities. This study aims to determine the phenological and pomological characteristics of the Foşa and Yomra hazelnut populations and reveal their genetic diversity using multivariate statistical analysis and Simple Sequence Repeat (SSR) molecular markers. We analyzed 80 accessions (43 Foşa and 37 Yomra) using 10 SSR primers to establish genetic relationships. The polymorphic band lengths ranged from 53 to 158 bp, with 1 to 8 bands per primer, totaling 45 bands. The average genetic diversity was 0.53, observed heterozygosity was 0.31, and the polymorphism rate was 0.48. Phylogenetic analysis clearly separated ‘Foşa’ and ‘Yomra’ varieties into distinct clusters, with the population dividing into two main groups, each further subdivided into two subgroups. Several accessions within different subgroups showed identical genetic profiles, indicating clonal relationships. Genetic variation within the ‘Yomra’ variety (similarity coefficient: 0.646) was slightly higher than in the ‘Foşa’ variety (0.676). Among quantitative traits, the coefficient of variation ranged from 2.57% (nut size) to 68.12% (fibrousness), with high variation observed in yield, nuts per cluster, nut weight, kernel weight, kernel shape apex index, kernel cavity, blanching rate, and fibrousness. Phenologically, the ‘Foşa’ population exhibited earlier male flowering, female flowering, and leaf budburst compared to ‘Yomra’, with both populations showing protandrous-homogamous flowering patterns. These results demonstrate that genetically distinct accessions within these populations should be conserved in genetic resource collections and can serve as valuable parents in breeding programs.

Yusuf Bilgen
Yaşar Akça
Kenan Yıldız
Kubilay Yıldırım


Investigating the performance of the fluorescent sensor g-C3N4/Fe/Cu in detecting the Tenofovir drug

Abstract: Abstract Tenofovir is an antiviral drug that prevents the replication of AIDS and hepatitis B viruses. To minimize the harmful side effects of the drug on the body, it is essential to determine its precise concentration in the blood. Fluorescence spectroscopy is a cost-effective and highly sensitive method for detecting drugs like tenofovir. In this study, carbon nitride (g-C3N4), a unique form of carbon known for its exceptional stability, high quantum efficiency and specific surface area, was used to create a C3N4/Fe/Cu sensor. The g-C3N4/Fe/Cu sensor was characterized using SEM, UV-VIS, PL, EDX, mapping and FT-IR methods. The influencing factors of C3N4/Fe/Cu response, such as pH, analyte concentration and temperature, were optimized during the experiments. Various concentrations of tenofovir were prepared in water and added to g-C3N4/Fe/Cu. The fluorescence intensity of the resulting solutions was analyzed using PL analysis at a wavelength of 463 nm under optimal conditions. The results confirmed the identification of tenofovir in pharmaceutical capsules within the concentration range of 5.0-700.0 µM using g-C3N4/Cu/Fe. A strong linear relationship with an R2 = 0.9304 and a LOD = 3.2 µM (signal-to-noise = 3) was achieved. Therefore, g-C3N4/Fe/Cu is recommended for tenofovir drug assay.

Nafiseh Hajian Afarani
Fatemeh Keshavarzi
Kahin Shahanipour
Seyed Amir Zarei


A multi-branch network for cooperative spectrum sensing via attention-based and CNN feature fusion

Abstract: Abstract In cognitive radio (CR) systems, the accurate detection of spectrum holes is a cornerstone for efficient spectrum utilization. However, the increasing complexity of CR environments, particularly those with multiple primary users (PUs), has made precise spectrum sensing a paramount challenge. To address this challenge, this study introduces the ATC model, a novel deep learning architecture that integrates a parallel combination of attention mechanism-based networks and a Convolutional Neural Network (CNN). This hybrid design enables the model to capture both spatial and temporal features from the distinct statistics of sensing signals, thereby enhancing the accuracy of spectrum state detection. The model employs a Graph Attention Network (GAT) to extract complex topological features from graph-structured data derived from received signal strength, dynamically highlighting the most relevant information. To complement this, a CNN processes the sample covariance matrix of sensing signals, unlocking localized statistical correlations and hierarchical feature representations by treating the matrix as an image. Temporal dynamics, such as PU activity patterns, are modeled using a Transformer encoder, which leverages a self-attention mechanism to learn sequential features effectively. The proposed model is evaluated using both simulated and real-world datasets. For the simulated datasets, the model is assessed and compared with baseline methods under multi-PU scenarios across different channel models. For the real-world dataset, the experimental setup is configured for a single-PU scenario due to practical data collection limitations. In both cases, the ATC model demonstrates improved performance over the benchmarked spectrum sensing methods, exhibiting higher accuracy and robustness within the respective evaluation settings.

Doi Thi Lan
Quan T. Ngo
Luong Vuong Nguyen
O-Joun Lee


Mcm5 mutation leads to silencing of Stat1-bcl2 which accelerating apoptosis of immature T lymphocytes with DNA damage

Abstract: Abstract Mutation in genes involved in DNA replication continuously disrupt DNA replication and give rise to genomic instability, a critical driver of oncogenesis. To prevent leukemia, immature T lymphocytes with genomic instability often undergo rapid cell death during development. However, the mechanism by which immature T lymphocytes undergo rapid cell death upon genomic instability has been enigmatic. Here we show that zebrafish mcm5 mutation leads to DNA damage in immature T lymphocytes and the immature T cells sensitively undergo rapid cell death. Detailed analyses demonstrated that the immature T lymphocytes undergo rapid apoptosis via upregulation of tp53 and downregulation of bcl2 transcription in mcm5 mutants. Mechanistically, Mcm5 directly binds to Stat1a and facilitates its phosphorylation to enhance bcl2a expression under the conditions of DNA replication stress. However, in mcm5 mutants, the absence of the Mcm5-Stat1 complex decreases Stat1 phosphorylation and subsequent bcl2a transcription, accelerating apoptosis of immature T lymphocytes with genomic instability. Furthermore, our study shows that the role of Mcm5 in T-cell development is conserved in mice. In conclusion, our work identifies a role of Mcm5 in regulating T cell development via Stat1-Bcl2 cascade besides its role in DNA replication, providing a kind of mechanism by which immature T cells with gene mutation-induced DNA damage are rapidly cleared during T lymphocyte development.

Min Liu
Yuanyuan Li
Zhilin Deng
Ke Zhang
Shuying Huang
Jiamin Xia
Yi Feng
Yundan Liang
Chengfu Sun
Xindong Liu
Shurong Li
Bingyin Su
Yong dong
Sizhou Huang


Modularity of Zorya defense systems during phage inhibition

Abstract: Abstract Bacteria have evolved an extraordinary diversity of defense systems against bacteriophage (phage) predation. However, the molecular mechanisms underlying these anti-phage systems often remain elusive. Here, we provide mechanistic and structural insights into Zorya phage defense systems. Using cryo-EM structural analyses, we show that the Zorya type I and II core components, ZorA and ZorB, assemble in a 5:2 complex that is similar to inner-membrane ion-driven, rotary motors that power flagellar rotation, type 9 secretion, gliding and the Ton nutrient uptake systems. The ZorAB complex has an elongated cytoplasmic tail assembled by bundling the C-termini of the five ZorA subunits. Mutagenesis demonstrates that peptidoglycan binding by the periplasmic domains of ZorB, the structured cytoplasmic tail of ZorA, and ion flow through the motor is important for function in both type I and II systems. Furthermore, we identify ZorE as the effector module of the Zorya II system, possessing nickase activity. Our work reveals the molecular basis of the activity of Zorya systems and highlights the ZorE nickase as crucial for population-wide immunity in the type II system.

Giuseppina Mariano
Justin C. Deme
Jennifer J. Readshaw
Matthew J. Grobbelaar
Mackenzie Keenan
Yasmin El-Masri
Lindsay Bamford
Suraj Songra
Tim R. Blower
Tracy Palmer
Susan M. Lea


Climate change, thermal anomalies, and the recent progression of dengue in Brazil

Abstract: Abstract Dengue is rapidly expanding its transmission area across Brazil and much of South America. In this study, data-mining techniques were used to identify climatic and demographic indicators that could explain the recent (2014–2020) and simultaneous trends of expansion and exacerbation of the incidence in some regions of Brazil. The previous circulation of the virus (dengue incidence rates between 2007 and 2013), urbanization, and the occurrence of temperature anomalies for a prolonged period were the main factors that led to increased incidence of dengue in the central region of Brazil. Regions with high altitudes, which previously acted as a barrier for dengue transmission, became areas of high incidence rates. The algorithm that was developed during this study can be utilized to assess future climate scenarios and plan preventive actions.

Christovam Barcellos
Vanderlei Matos
Raquel Martins Lana
Rachel Lowe


Breaking of Henry’s law for sulfide liquid–basaltic melt partitioning of Pt and Pd

Abstract: Platinum group elements are used as tracers for planetary and PGE sulfide deposit formation. Here, the authors, through the measurements of Pt and Pd partition coefficients between sulfide liquid and basaltic melt, demonstrate that the partitioning of Pt and Pd does not obey Henry’s law.


Metabolic Profiling of Volatile Organic Compounds (VOCs) Emitted by the Pathogens Francisella tularensis and Bacillus anthracis in Liquid Culture

Abstract: Abstract We conducted comprehensive (untargeted) metabolic profiling of volatile organic compounds (VOCs) emitted in culture by bacterial taxa Francisella tularensis (F. tularensis) subspecies novicida and Bacillus anthracis (B. anthracis) Sterne, surrogates for potential bacterial bioterrorism agents, as well as selective measurements of VOCs from their fully virulent counterparts, F. tularensis subspecies tularensis strain SCHU S4 and B. anthracis Ames. F. tularensis and B. anthracis were grown in liquid broth for time periods that covered logarithmic growth, stationary, and decline phases. VOCs emitted over the course of the growth phases were collected from the headspace above the cultures using solid phase microextraction (SPME) and were analyzed using gas chromatography-mass spectrometry (GC-MS). We developed criteria for distinguishing VOCs originating from bacteria versus background VOCs (originating from growth media only controls or sampling devices). Analyses of collected VOCs revealed methyl ketones, alcohols, esters, carboxylic acids, and nitrogen- and sulfur-containing compounds that were present in the bacterial cultures and absent (or present at only low abundance) in control samples indicating that these compounds originated from the bacteria. Distinct VOC profiles where observed for F. tularensis when compared with B. anthracis while the observed profiles of each of the two F. tularensis and B. anthracis strains exhibited some similarities. Furthermore, the relative abundance of VOCs was influenced by bacterial growth phase. These data illustrate the potential for VOC profiles to distinguish pathogens at the genus and species-level and to discriminate bacterial growth phases. The determination of VOC profiles lays the groundwork for non-invasive probes of bacterial metabolism and offers prospects for detection of microbe-specific VOC biomarkers from two potential biowarfare agents.

Kristen L. Reese
Amy Rasley
Julie R. Avila
A. Daniel Jones
Matthias Frank


Detecting outliers in segmented genomes of flu virus using an alignment-free approach

Abstract: In this paper, we propose a new approach to detecting outliers in a set of segmented genomes of the flu virus, a data set with a heterogeneous set of sequences. The approach has the following computational phases: feature extraction, which is a mapping into feature space, alignment-free distance measure to measure the distance between any two segmented genomes, and a mapping into distance space to analyze a quantum of distance values. The approach is implemented using supervised and unsupervised learning modes. The experiments show robustness in detecting outliers of the segmented genome of the flu virus.


Bioregulatory event extraction using large language models: a case study of rice literature

Abstract: Abstract The extraction of biological regulation events has been a key focus in the field of biomedical nature language processing (BioNLP). However, existing methods often encounter challenges such as cascading errors in text mining pipelines and limitations in topic coverage from the selected corpus. Fortunately, the emergence of large language models (LLMs) presents a potential solution due to their robust semantic understanding and extensive knowledge base. To explore this potential, our project at the Biomedical Linked Annotation Hackathon 8 (BLAH 8) investigates the feasibility of using LLMs to extract biological regulation events. Our findings, based on the analysis of rice literature, demonstrate the promising performance of LLMs in this task, while also highlighting several concerns that must be addressed in future LLM-based application in low-resource topic.


The interaction between gut microbiome and nutrients on development of human disease through epigenetic mechanisms

Abstract: Early environmental exposure is recognized as a key factor for long-term health based on the Developmental Origins of Health and Disease hypothesis. It considers that early-life nutrition is now being recognized as a major contributor that may permanently program change of organ structure and function toward the development of diseases, in which epigenetic mechanisms are involved. Recent researches indicate early-life environmental factors modulate the microbiome development and the microbiome might be mediate diet-epigenetic interaction. This review aims to define which nutrients involve microbiome development during the critical window of susceptibility to disease, and how microbiome modulation regulates epigenetic changes and influences human health and future prevention strategies.


Genome Architecture and Its Roles in Human Copy Number Variation

Abstract: Besides single-nucleotide variants in the human genome, large-scale genomic variants, such as copy number variations (CNVs), are being increasingly discovered as a genetic source of human diversity and the pathogenic factors of diseases. Recent experimental findings have shed light on the links between different genome architectures and CNV mutagenesis. In this review, we summarize various genomic features and discuss their contributions to CNV formation. Genomic repeats, including both low-copy and high-copy repeats, play important roles in CNV instability, which was initially known as DNA recombination events. Furthermore, it has been found that human genomic repeats can also induce DNA replication errors and consequently result in CNV mutations. Some recent studies showed that DNA replication timing, which reflects the high-order information of genomic organization, is involved in human CNV mutations. Our review highlights that genome architecture, from DNA sequence to high-order genomic organization, is an important molecular factor in CNV mutagenesis and human genomic instability.

Lu Chen
Weichen Zhou
Ling Zhang
Feng Zhang


Relevance Epistasis Network of Gastritis for Intra-chromosomes in the Korea Associated Resource (KARE) Cohort Study

Abstract: Gastritis is a common but a serious disease with a potential risk of developing carcinoma. Helicobacter pylori infection is reported as the most common cause of gastritis, but other genetic and genomic factors exist, especially single-nucleotide polymorphisms (SNPs). Association studies between SNPs and gastritis disease are important, but results on epistatic interactions from multiple SNPs are rarely found in previous genome-wide association (GWA) studies. In this study, we performed computational GWA case-control studies for gastritis in Korea Associated Resource (KARE) data. By transforming the resulting SNP epistasis network into a gene-gene epistasis network, we also identified potential gene-gene interaction factors that affect the susceptibility to gastritis.


Understanding Epistatic Interactions between Genes Targeted by Non-coding Regulatory Elements in Complex Diseases

Abstract: Genome-wide association studies have proven the highly polygenic architecture of complex diseases or traits; therefore, single-locus-based methods are usually unable to detect all involved loci, especially when individual loci exert small effects. Moreover, the majority of associated single-nucleotide polymorphisms resides in non-coding regions, making it difficult to understand their phenotypic contribution. In this work, we studied epistatic interactions associated with three common diseases using Korea Association Resource (KARE) data: type 2 diabetes mellitus (DM), hypertension (HT), and coronary artery disease (CAD). We showed that epistatic single-nucleotide polymorphisms (SNPs) were enriched in enhancers, as well as in DNase I footprints (the Encyclopedia of DNA Elements [ENCODE] Project Consortium 2012), which suggested that the disruption of the regulatory regions where transcription factors bind may be involved in the disease mechanism. Accordingly, to identify the genes affected by the SNPs, we employed whole-genome multiple-cell-type enhancer data which discovered using DNase I profiles and Cap Analysis Gene Expression (CAGE). Assigned genes were significantly enriched in known disease associated gene sets, which were explored based on the literature, suggesting that this approach is useful for detecting relevant affected genes. In our knowledge-based epistatic network, the three diseases share many associated genes and are also closely related with each other through many epistatic interactions. These findings elucidate the genetic basis of the close relationship between DM, HT, and CAD.

Min Kyung Sung
Hyoeun Bang
Jung Kyoon Choi


BioOne: a national-scale platform for integrated discovery and utilization of diverse biological resources in South Korea

Abstract: Abstract The rapid growth of biological resources and associated research outputs has increased the complexity of resource discovery, access, and reuse across heterogeneous repositories. However, fragmented metadata schemas, limited interoperability, and siloed access mechanisms continue to hinder the integrated exploration of biological resources and their associated knowledge. Herein, we present BioOne (Biological resources One-Stop service platform), a unified informatics framework designed to address the fragmentation of national biological resources by integrating heterogeneous metadata from 14 distinct clusters and establishing a seamless resource-to-knowledge pipeline to enhance the discoverability and practical utilization of biological assets. BioOne is a national-scale web-based discovery platform that harmonizes biological resource metadata across 14 domain-specific biological resource clusters in Korea and systematically links these resources with external knowledge objects, including research papers, patents, biological datasets, and disease–drug–target information, through a unified discovery interface. To achieve this, we adopted a standard-aligned metadata integration framework, interoperable identifier mapping, and a modular system architecture to support scalable indexing, cross-domain search, and association-based navigation. By extending conventional catalog-based biological resource databases with an integrated discovery and access layer connecting distributed biorepositories to evidence-oriented knowledge resources, BioOne provides an informatics infrastructure for data-driven discovery, translational research, and coordinated utilization of biological resources at the national scale. The BioOne also offers a transferable implementation model for the large-scale integration of distributed biological resource systems.

Tae-Ho Kang
KyoungSoo Ha
WonHyun Kyung
Yong-Jin Jeon
Geun-Hyoung Jo
KangMin Park
KwangHee Lee
Tae-Eun Jin


Discovery and Evaluation of Polymorphisms in the  and  Promoter Regions for Risk of Korean Lung Cancer

Abstract: AKT is a signal transduction protein that plays a central role in the tumorigenesis. There are 3 mammalian isoforms of this serine/threonine protein kinase-AKT1, AKT2, and AKT3-showing a broad tissue distribution. We first discovered 2 novel polymorphisms (AKT2 -9826 C/G and AKT3 -811 A/G), and we confirmed 6 known polymorphisms (AKT2 -9473 C/T, AKT2 -9151 C/T, AKT2 -9025 C/T, AKT2 -8618G/A, AKT3 -675 A/-, and AKT3 -244 C/T) of the AKT2 and AKT3 promoter region in 24 blood samples of Korean lung cancer patients using direct sequencing. To evaluate the role of AKT2 and AKT3 polymorphisms in the risk of Korean lung cancer, genotypes of the AKT2 and AKT3 polymorphisms (AKT2 -9826 C/G, AKT2 -9473 C/T, AKT2 -9151 C/T, AKT2 -9025 C/T, AKT2 -8618G/A, and AKT3 -675 A/-) were determined in 360 lung cancer patients and 360 normal controls. Statistical analyses revealed that the genotypes and haplotypes in the AKT2 and AKT3 promoter regions were not significantly associated with the risk of lung cancer in the Korean population. These results suggest that polymorphisms of the AKT2 and AKT3 promoter regions do not contribute to the genetic susceptibility to lung cancer in the Korean population.

Jae Sook Sung
Kyong Hwa Park
Seung Tae Kim
Yeul Hong Kim


Human Transcriptome and Chromatin Modifications: An ENCODE Perspective

Abstract: A decade-long project, led by several international research groups, called the Encyclopedia of DNA Elements (ENCODE), recently released an unprecedented amount of data. The ambitious project covers transcriptome, cistrome, epigenome, and interactome data from more than 1,600 sets of experiments in human. To make use of this valuable resource, it is important to understand the information it represents and the techniques that were used to generate these data. In this review, we introduce the data that ENCODE generated, summarize the observations from the data analysis, and revisit a computational approach that ENCODE used to predict gene expression, with a focus on the human transcriptome and its association with chromatin modifications.

Li Shen
Inchan Choi
Eric J. Nestler
Kyoung-Jae Won


Sequence Analysis of Hypothetical Proteins from  26695 to Identify Potential Virulence Factors

Abstract: Helicobacter pylori is a Gram-negative bacteria that is responsible for gastritis in human. Its spiral flagellated body helps in locomotion and colonization in the host environment. It is capable of living in the highly acidic environment of the stomach with the help of acid adaptive genes. The genome of H. pylori 26695 strain contains 1,555 coding genes that encode 1,445 proteins. Out of these, 340 proteins are characterized as hypothetical proteins (HP). This study involves extensive analysis of the HPs using an established pipeline which comprises various bioinformatics tools and databases to find out probable functions of the HPs and identification of virulence factors. After extensive analysis of all the 340 HPs, we found that 104 HPs are showing characteristic similarities with the proteins with known functions. Thus, on the basis of such similarities, we assigned probable functions to 104 HPs with high confidence and precision. All the predicted HPs contain representative members of diverse functional classes of proteins such as enzymes, transporters, binding proteins, regulatory proteins, proteins involved in cellular processes and other proteins with miscellaneous functions. Therefore, we classified 104 HPs into aforementioned functional groups. During the virulence factors analysis of the HPs, we found 11 HPs are showing significant virulence. The identification of virulence proteins with the help their predicted functions may pave the way for drug target estimation and development of effective drug to counter the activity of that protein.

Ahmad Abu Turab Naqvi
Farah Anjum
Faez Iqbal Khan
Asimul Islam
Faizan Ahmad
Md. Imtaiyaz Hassan


Intestinal barrier defense: the protective effect of plant-based traditional Chinese medicine

Abstract: Abstract Traditional Chinese medicine (TCM) plays a crucial role in maintaining the intestinal barrier, which is considered integral to overall health and is connected with the functions of the spleen and stomach and the balance of qi and blood. TCM principles, such as "separating the pure from the turbid," are related to gut flora equilibrium, with imbalances corresponding to the "struggle between good and evil." TCM supports the intestinal barrier through methods such as invigorating qi and strengthening the spleen. In this review, authoritative databases such as PubMed, Web of Science, and Google Scholar were systematically searched for studies on the protective effects of TCM and its constituents on the intestinal barrier from 2018 to 2025. The results show that TCM and its components have multiple advantages in maintaining intestinal barrier function. Classic formulations such as Qingchang Wenzhong and Huangqin decoction protect the intestines through various pathways, including regulating the gut microbiota and enhancing immune function. Single herbs such as Coptis chinensis (Huang Lian) and Scutellaria baicalensis (Huang Qin), whose properties include clearing heat and detoxifying and tonifying qi, directly or indirectly promote intestinal health. Additionally, active compounds in TCM, such as flavonoids and saponins, contribute to intestinal homeostasis through mechanisms such as anti-inflammatory and antioxidant effects. The multicomponent, multitarget characteristics of TCM provide comprehensive and long-lasting efficacy in intestinal barrier protection. This article summarizes the current research status of TCM in treating intestinal barrier injury and highlights future research directions, offering a theoretical foundation and research insights for further exploration of the role of TCM in safeguarding intestinal barrier function. Graphical Abstract

Shaofeng Wu
Yu Ga
Danyang Ma
Silu Hou
Qiaoyue Hui
Zhihui Hao

Physical anthropology. Somatology
Veterinary medicine


Unraveling antibiotic resistance dynamics at the soil–plant interface under climate change for One Health

Abstract: Abstract Antibiotic resistance genes (ARGs) naturally serve ecological and adaptive functions in microorganisms, yet human activities have disrupted this balance, accelerating their enrichment and spread in the soil–plant system. As a key ARG transmission interface across One Health sectors, the soil–plant system warrants greater attention. This review synthesizes emerging evidence on the distribution and transmission of resistomes in the rhizosphere, phyllosphere, and endosphere, revealing the potential risk of soil–plant ARGs to human, animal, and plant health. However, major gaps remain, particularly in horizontal and vertical ARG transmission associated within the plant endosphere and across plant generations. Moreover, we summarize key factors shaping soil–plant ARG dynamics, including soil conditions, plant evolution and traits, and anthropogenic influences. Among these, climate change emerges as a global, long-term, and largely irreversible driver, altering soil properties, plant physiology, and microbial activity through drastic environmental shifts. We discuss the risks of climate-driven ARG dissemination and its broader ecological and agricultural implications. Addressing these challenges requires advanced monitoring methods, integrated data sources, and policy innovations. In this review, we highlight climate change as an emerging driver of ARG selection and dissemination, emphasizing its impact on soil–plant resistome and the need for future One Health research on climate-driven resistome shifts.

Xinyuan Li
Samuel Bickel
Wisnu Adi Wicaksono
Xianyong Lin
Gabriele Berg
Yongguan Zhu


Organizing an in-class hackathon to correct PDF-to-text conversion errors of  1.0

Abstract: This paper describes a community effort to improve earlier versions of the full-text corpus of Genomics & Informatics by semi-automatically detecting and correcting PDF-to-text conversion errors and optical character recognition errors during the first hackathon of Genomics & Informatics Annotation Hackathon (GIAH) event. Extracting text from multi-column biomedical documents such as Genomics & Informatics is known to be notoriously difficult. The hackathon was piloted as part of a coding competition of the ELTEC College of Engineering at Ewha Womans University in order to enable researchers and students to create or annotate their own versions of the Genomics & Informatics corpus, to gain and create knowledge about corpus linguistics, and simultaneously to acquire tangible and transferable skills. The proposed projects during the hackathon harness an internal database containing different versions of the corpus and annotations.

Sunho Kim
Royoung Kim
Hee-Jo Nam
Ryeo-Gyeong Kim
Enjin Ko
Han-Su Kim
Jihye Shin
Daeun Cho
Yurhee Jin
Soyeon Bae
Ye Won Jo
San Ah Jeong
Yena Kim
Seoyeon Ahn
Bomi Jang
Jiheyon Seong
Yujin Lee
Si Eun Seo
Yujin Kim
Ha-Jeong Kim
Hyeji Kim
Hye-Lynn Sung
Hyoyoung Lho
Jaywon Koo
Jion Chu
Juwon Lim
Youngju Kim
Kyungyeon Lee
Yuri Lim
Meongeun Kim
Seonjeong Hwang
Shinhye Han
Sohyeun Bae
Sua Kim
Suhyeon Yoo
Yeonjeong Seo
Yerim Shin
Yonsoo Kim
You-Jung Ko
Jihee Baek
Hyejin Hyun
Hyemin Choi
Ji-Hye Oh
Da-Young Kim
Hyun-Seok Park


VBioindex: A Visual Tool to Estimate Biodiversity

Abstract: Biological diversity, also known as biodiversity, is an important criterion for measuring the value of an ecosystem. As biodiversity is closely related to human welfare and quality of life, many efforts to restore and maintain the biodiversity of species have been made by government agencies and non-governmental organizations, thereby drawing a substantial amount of international attention. In the fields of biological research, biodiversity is widely measured using traditional statistical indices such as the Shannon-Wiener index, species richness, evenness, and relative dominance of species. However, some biologists and ecologists have difficulty using these indices because they require advanced mathematical knowledge and computational techniques. Therefore, we developed VBioindex, a user-friendly program that is capable of measuring the Shannon-Wiener index, species richness, evenness, and relative dominance. VBioindex serves as an easy to use interface and visually represents the results in the form of a simple chart and in addition, VBioindex offers functions for long-term investigations of datasets using time-series analyses.


Editor's Introduction to This Issue


Altered RBC aggregability in diabetes: a threshold for pathophysiological structure-function RBC changes

Abstract: Abstract Objective Vascular complications have been associated with pathophysiological RBC changes including reduced RBC deformability (RBCD): the ability of RBCs to change their shape in the microvasculature and increased red blood cell aggregability (RBCA): the tendency of RBCs to form aggregates (rouleaux). However, understanding of aberrant RBCA in diabetes and its relationship with RBCD is limited. We investigated clinical and RBC structural and functional changes associated with RBCA in comparison with RBCD. Methods We conducted an outpatient cross-sectional study of participants with diabetes (n = 81) and nondiabetic controls (n = 78) at the National Institutes of Health. Clinical history was obtained using standardized forms, fasting blood and urine samples were collected for clinical laboratory measurements and ektacytometry studies of RBC physiological parameters: RBCA, RBCD and osmotic fragility. Functional RBC changes were assessed using hemoglobin-oxygen dissociation (p50). Major outcomes assessed differences in RBCA Aggregation Index (AI), with increased RBCA defined as higher AI. Exploratory outcomes assessed differences in subgroups with type 1 (T1D) and type 2 (T2D) diabetes, and associations with clinical, inflammatory, endocrine and RBC physiological parameters. Outcomes were assessed using both nonparametric and multivariable regression methods. Results Compared with controls, AI was significantly higher in the diabetes cohort (75±8 vs 71 ± 11, p = 0.007), T2D (77±7 vs 71 ± 11, p < 0.001), but not T1D (69±7 vs 71 ± 11, p = 0.242). While RBCD values were similar in T1D and T2D (p = 0.31), mean AI value was significantly higher in T2D vs T1D (p = 0.02). In contrast to RBCD, AI was associated with T2D (p < 0.001), BMI (p < 0.001), insulin resistance (HOMA-IR, p = 0.033), leptin (p < 0.001), C-peptide levels (p = 0.009), but not vascular complications (p = 0.156). While RBCA and RBCD were associated with CRP (p < 0.001 and p = 0.005 respectively), neither was associated with fibrinogen (p = 0.768 and p = 0.118 respectively). In contrast to RBCD, AI was associated with increased osmotic fragility (p < 0.001) and a threshold of altered hemoglobin-oxygen dissociation (p50) estimated at AI of 75 in both groups using piecewise linear statistical modeling. Thus, AI was positively correlated with p50 at AI < 75 (p = 0.033) and negatively correlated at AI ≥ 75 (p = 0.007). Conclusions Findings show that in contrast to RBCD, RBCA is characterized by a RBC functional threshold beyond which oxygen release is reduced, and RBC structure-function relationship likely modulated by insulin resistance and pro-inflammatory endocrine factors. The distinct but complementary and synergistic changes in RBCD and RBCA provide a framework for strategies aimed at mitigation of vascular risk in diabetes.

Ifechukwude Ebenuwa
Pierre-Christian Violet
Stephanie Teng
Thom Greene
Nicholas Munyan
Razi Berman
Irene Rozga
Mary Walter
Kenneth J. Wilkins
Nermi Parrow
Mark Levine

Cardiovascular Diabetology. Endocrinology Reports


Editor’s Introduction to This Issue (G&I 15:3, 2017)


FusionScan: accurate prediction of fusion genes from RNA-Seq data

Abstract: Identification of fusion gene is of prominent importance in cancer research field because of their potential as carcinogenic drivers. RNA sequencing (RNA-Seq) data have been the most useful source for identification of fusion transcripts. Although a number of algorithms have been developed thus far, most programs produce too many false-positives, thus making experimental confirmation almost impossible. We still lack a reliable program that achieves high precision with reasonable recall rate. Here, we present FusionScan, a highly optimized tool for predicting fusion transcripts from RNA-Seq data. We specifically search for split reads composed of intact exons at the fusion boundaries. Using 269 known fusion cases as the reference, we have implemented various mapping and filtering strategies to remove false-positives without discarding genuine fusions. In the performance test using three cell line datasets with validated fusion cases (NCI-H660, K562, and MCF-7), FusionScan outperformed other existing programs by a considerable margin, achieving the precision and recall rates of 60% and 79%, respectively. Simulation test also demonstrated that FusionScan recovered most of true positives without producing an overwhelming number of false-positives regardless of sequencing depth and read length. The computation time was comparable to other leading tools. We also provide several curative means to help users investigate the details of fusion candidates easily. We believe that FusionScan would be a reliable, efficient and convenient program for detecting fusion transcripts that meet the requirements in the clinical and experimental community. FusionScan is freely available at http://fusionscan.ewha.ac.kr/.


HisCoM-GGI: Software for Hierarchical Structural Component Analysis of Gene-Gene Interactions

Abstract: Gene-gene interaction (GGI) analysis is known to play an important role in explaining missing heritability. Many previous studies have already proposed software to analyze GGI, but most methods focus on a binary phenotype in a case-control design. In this study, we developed “Hierarchical structural CoMponent analysis of Gene-Gene Interactions” (HisCoM-GGI) software for GGI analysis with a continuous phenotype. The HisCoM-GGI method considers hierarchical structural relationships between genes and single nucleotide polymorphisms (SNPs), enabling both gene-level and SNP-level interaction analysis in a single model. Furthermore, this software accepts various types of genomic data and supports data management and multithreading to improve the efficiency of genome-wide association study data analysis. We expect that HisCoM-GGI software will provide advanced accessibility to researchers in genetic interaction studies and a more effective way to understand biological mechanisms of complex diseases.

Sungkyoung Choi
Sungyoung Lee
Taesung Park


Editor's Introduction to This Issue (G&I 15:1, 2017)


Roles of Oncogenic Long Non-coding RNAs in Cancer Development

Abstract: Long non-coding RNAs (lncRNAs) are classified as RNAs that are longer than 200 nucleotides and cannot be translated into protein. Several studies have demonstrated that lncRNAs are directly or indirectly involved in a variety of biological processes and in the regulation of gene expression. In addition, lncRNAs have important roles in many diseases including cancer. It has been shown that abnormal expression of lncRNAs is observed in several human solid tumors. Several studies have shown that many lncRNAs can function as oncogenes in cancer development through the induction of cell cycle progression, cell proliferation and invasion, anti-apoptosis, and metastasis. Oncogenic lncRNAs have the potential to become promising biomarkers and might be potent prognostic targets in cancer therapy. However, the biological and molecular mechanisms of lncRNA involvement in tumorigenesis have not yet been fully elucidated. This review summarizes studies on the regulatory and functional roles of oncogenic lncRNAs in the development and progression of various types of cancer.


Emergence of bla NDM-5-carrying Pseudescherichia vulneris and Pantoea dispersa isolated from the veterinary hospital environment

Abstract: Abstract The emergence of carbapenem-resistant Enterobacterales (CRE) poses a critical threat to global health security. Veterinary hospitals may serve as potential hotspots for antimicrobial resistance (AMR) gene dissemination, yet surveillance in these environments remains limited. This study was carried out to screen the spread of CRE in the environment of a veterinary hospital. Totally, we collected 283 environmental swab samples from a veterinary hospital in Guangzhou, China. The samples were screened for meropenem-resistant isolates, and polymerase chain reaction amplification was performed to detect bla NDM genes. Species identification was performed using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Two isolates representing previously unreported bla NDM-positive species were selected for whole-genome sequencing. Thirty-two meropenem-resistant isolates were recovered, with 15 isolates (5.3%) testing positive for bla NDM genes. All the bla NDM-positive isolates belonged to Enterobacterales, including one isolate each of Pseudescherichia vulneris and Pantoea dispersa, representing the first reported bla NDM-positive strains of these species. Whole-genome sequencing of these two isolates revealed that both harbored bla NDM-5 genes on IncX3 plasmids with conjugation frequencies of 7.5 × 10⁻5 and 6.0 × 10⁻5, respectively. The P. dispersa strain exhibited high genetic similarity (core-genome single nucleotide polymorphisms = 12) to isolates of Oryza sativa origin from India lacking bla NDM genes, suggesting recent plasmid acquisition. The detection of bla NDM-5 in these previously unreported host species is concerning given their exceptional environmental persistence and stress tolerance. These findings highlight the urgent need for enhanced One Health surveillance approaches encompassing veterinary environments as critical components of AMR networks.

Zhongpeng Cai
Weihang Liu
Xinger Wen
Bingqing Zhu
Luchao Lv
Zhiwen Wu
Chanping Zhi


An Efficient Approach to Mining Maximal Contiguous Frequent Patterns from Large DNA Sequence Databases

Abstract: Mining interesting patterns from DNA sequences is one of the most challenging tasks in bioinformatics and computational biology. Maximal contiguous frequent patterns are preferable for expressing the function and structure of DNA sequences and hence can capture the common data characteristics among related sequences. Biologists are interested in finding frequent orderly arrangements of motifs that are responsible for similar expression of a group of genes. In order to reduce mining time and complexity, however, most existing sequence mining algorithms either focus on finding short DNA sequences or require explicit specification of sequence lengths in advance. The challenge is to find longer sequences without specifying sequence lengths in advance. In this paper, we propose an efficient approach to mining maximal contiguous frequent patterns from large DNA sequence datasets. The experimental results show that our proposed approach is memory-efficient and mines maximal contiguous frequent patterns within a reasonable time.

Md. Rezaul Karim
Md. Mamunur Rashid
Byeong-Soo Jeong
Ho-Jin Choi


Prevalence, antimicrobial resistance patterns, and associated factors of Staphylococcus aureus among different clinical specimens in Wad Medani, Sudan: a four-year, laboratory-based, retrospective study

Abstract: Abstract Staphylococcus aureus is a significant pathogen in clinical settings and community. Therefore, this laboratory-based, retrospective study assessed the prevalence, patterns of antimicrobial resistance, and associated factors of S. aureus. The study included all clinical samples collected by the Pathology Center for Diagnosis and Research (PCDR), University of Gezira in Sudan for culture and drug sensitivity from January 2020 to October 2023. Data were collected manually from PCDR registries. In total, 1784 clinical specimens exhibited bacterial growth. The overall S. aureus isolation rate was 39.1% (697/1784). The strains were primarily isolated from female patients (79.5%, 554/697), 38.9% of whom (271/697) were aged 30–44 years. S. aureus strains were most commonly isolated from urine samples (n = 465, 66.7%) and wound swabs (n = 150, 21.5%). The resistance rates were highest for tetracycline (55.1%, 201/365), erythromycin (51.3%, 141/275), vancomycin (49%, 118/241) and lowest for nitrofurantoin (7%, 11/157) and chloramphenicol (19.25%, 15/78). Multivariable binary logistic regression revealed associations of patient age, year of isolation, and sample type with S. aureus infection. This study reported a moderate prevalence of S. aureus that significantly increased over time. Additional investigations using an alternative method are required to verify the observed resistance of S. aureus to vancomycin.

Yousif B. Hamadalneel
Marwa F. Alamin
Hifa O. Ahmed
Safa F. Eltoum
Elmuntasir Elamin


AMP-CapsNet: a multi-view feature fusion approach for antimicrobial peptide prediction using capsule networks

Abstract: Abstract Antimicrobial peptides (AMPs) are universally found in both intracellular and extracellular settings and have significant antibiotic-resistant bacteria are becoming a bigger problem. In medical laboratories, it has shown notable anti-bacterial effectiveness in treating diabetic foot infections and related issues. New medication development frequently targets (AMPs), which are certainly ensuing components of adaptive immune system. The findings of this research employs deep learning to identify antibiotic activity. Numerous computational methods have been established to detect antimicrobial peptides via deep learning algorithms. We introduced a novel deep learning approach called antimicrobial peptides using Capsule Neural Network (AMP-CapsNet) to precisely forecast them and evaluated its efficacy against deep learning and baseline models. AMPs prediction using capsule neural networks, a type of next generation neural network, to build prediction models. Additionally, we utilized Amino Acid Composition (AAC) for effective features encoded method and as well as dipeptide composition (DPC). Every model underwent independent cross-validation and external testing. The findings indicate that the enhanced AMP-CapsNet deep learning model surpassed its counterparts, achieving an accuracy of 97.29% and an AUC score of 98.91% on the test set using with dipeptide Composition (DPC). The proposed AMP-CapsNet demonstrates superior performance of the testing set achieved accuracy 97.29% score with DPC and accuracy 84.42% score with AAC approach. Consequently, the technique we advocate is anticipated to enhance the accuracy of antimicrobial peptide predictions in the future. By producing powerful peptides for medication development and application, this study advances deep learning-based AMP drug discovery approaches. This finding has important ramifications for how biological data is processed and how pharmacology is calculated.

Ali Ghulam
Mujeebu Rehman
Huma Fida
Pei-Yu Zhao
Ramsha Noroze
Ye-Chen Qi
Xiao-Long Yu


Dissecting non-B DNA structural motifs in untranslated regions of eukaryotic genomes

Abstract: Abstract The untranslated regions (UTRs) of genes significantly impact various biological processes, including transcription, posttranscriptional control, mRNA stability, localization, and translation efficiency. In functional areas of genomes, non-B DNA structures such as cruciform, curved, triplex, G-quadruplex, and Z-DNA structures are common and have an impact on cellular physiology. Although the role of these structures in cis-regulatory regions such as promoters is well established in eukaryotic genomes, their prevalence within UTRs across different eukaryotic classes has not been extensively documented. Our study investigated the prevalence of various non-B DNA motifs within the 5′ and 3′ UTRs across diverse eukaryotic species. Our comparative analysis encompassed the 5′-UTRs and 3′UTRs of 360 species representing diverse eukaryotic domains of life, including Arthropoda (Diptera, Hemiptera, and Hymenoptera), Chordata (Artiodactyla, Carnivora, Galliformes, Passeriformes, Primates, Rodentia, Squamata, Testudines), Magnoliophyta (Brassicales), Fabales (Poales), and Nematoda (Rhabditida), on the basis of datasets derived from the UTRdb. We observed that species belonging to taxonomic orders such as Rhabditida, Diptera, Brassicales, and Hemiptera present a prevalence of curved DNA motifs in their UTRs, whereas orders such as Testudines, Galliformes, and Rodentia present a preponderance of G-quadruplexes in both UTRs. The distribution of motifs is conserved across different taxonomic classes, although species-specific variations in motif preferences were also observed. Our research unequivocally illuminates the prevalence and potential functional implications of non-B DNA motifs, offering invaluable insights into the evolutionary and biological significance of these structures.

Aruna Sesha Chandrika Gummadi
Divya Kumari Muppa
Venakata Rajesh Yella


ENCODE: A Sourcebook of Epigenomes and Chromatin Language

Abstract: Until recently, since the Human Genome Project, the general view has been that the majority of the human genome is composed of junk DNA and has little or no selective advantage to the organism. Now we know that this conclusion is an oversimplification. In April 2003, the National Human Genome Research Institute (NHGRI) launched an international research consortium called Encyclopedia of DNA Elements (ENCODE) to uncover non-coding functional elements in the human genome. The result of this project has identified a set of new DNA regulatory elements, based on novel relationships among chromatin accessibility, histone modifications, nucleosome positioning, DNA methylation, transcription, and the occupancy of sequence-specific factors. The project gives us new insights into the organization and regulation of the human genome and epigenome. Here, we sought to summarize particular aspects of the ENCODE project and highlight the features and data that have recently been released. At the end of this review, we have summarized a case study we conducted using the ENCODE epigenome data.


Trends in the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists among ischemic stroke patients

Abstract: Abstract Background Stroke is a leading cause of death and disability. Trials suggest that sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-receptor-1 receptor agonists (GLP-1 RAs) reduce cardiovascular risk in selected populations. Objectives To describe facility-level use of SGLT-2i/GLP-1 RAs among patients hospitalized with ischemic stroke in the US Department of Veterans Affairs (VA) hospitals and to examine facility determinants of prescribing. Methods We performed a retrospective trend analysis across 88 VA facilities (fiscal years 2020–2023). Prescribing was ascertained from VA pharmacy data; the outcome was the proportion of ischemic-stroke admissions receiving an SGLT-2i or GLP-1 RA. Facility-level binomial logistic models evaluated associations with VA hospital complexity (1, high; 2, low complexity), rural-serving, and volume. Results Among 17,093 admissions, facility-level prescribing ranged from 13.2% to 38.3%. Overall use increased from 21.8% (2020) to 30.1% (2023; P < 0.001), driven largely by patients with diabetes (38.9% to 51.5%); rates also increased in overweight patients (27.1% to 34.3%) but remained low in those without diabetes or overweight (3.4% to 7.0%, P = 0.010). Across years, 45.7% of patients with diabetes received therapy versus 7.8% without diabetes. In adjusted analyses, prescribing rates were lower at complexity 1b (OR 0.8, 95% CI 0.66–0.96) and 1c (OR 0.69, 95%CI 0.58–0.83) versus 2; rural-serving and volume were not associated with prescribing. Conclusions Use of SGLT-2i/GLP-1 RAs among patients with ischemic stroke increased modestly but remained low in those without diabetes. Substantial between-facility variation—particularly low prescribing rates at complexity class 1b/1c sites—highlights the need for future studies to evaluate barriers in prescribing. Trial registration ClinicalTrials.gov NCT04322162. Registration Date of 04/02/2020.

Qinglan Ding
Jason J. Sico
Anthony J. Perkins
Laura J. Myers
Joanne K. Daggy
Ali Sexson
Stanley E. Taylor
Laura Burrone
Kimberly Waddell
Dawn M. Bravata


Application of boron-dipyrromethene-labeled erythromycin for macrolide detection with fluorescence polarization immunoassay

Abstract: Abstract Immune assays are widely used in various fields of medicine, including enzyme-linked immunosorbent assays, fluorescence polarization immunoassay (FPIA), and immunochromatographic analysis. FPIA allows for high specificity and sensitivity detection of low-molecular-weight analytes in a homogeneous medium without separation; it has high accuracy and label stability, and analysis is fast, simple, and can be automated. A fluorescently labeled tracer for erythromycin determination with a new boron-dipyrromethene (BODIPY) dye was developed in this study. A pair of immunoreagents (tracers and antibodies) for detecting erythromycin was selected and characterized, and FPIA conditions were optimized for an analysis time of 5 min. Calibration curves were obtained, and FPIA analytical characteristics were determined. The limit of detection was 1.6 ng/mL with a detection range at pH 7.4 of 5 − 300 ng/mL. The developed FPIA was successfully used to determine erythromycin concentration in water and milk, with a recovery of 80% – 120%. Overall, an FPIA method for erythromycin determination was developed, the advantages of using the new BODIPY fluorescent label were shown, the accuracy of the method was verified by an recovery test, and real water samples were tested.

Liliya I. Mukhametova
Dmitrii A. Arutyunyan
Anastasia V. Shishkina
Andrei G. Tereshchenkov
Natalia V. Sumbatyan
Inna A. Galvidis
Maksim A. Burkin
Sergei A. Eremin


Structural Analysis of Recombinant Human Preproinsulins by Structure Prediction, Molecular Dynamics, and Protein-Protein Docking

Abstract: More effective production of human insulin is important, because insulin is the main medication that is used to treat multiple types of diabetes and because many people are suffering from diabetes. The current system of insulin production is based on recombinant DNA technology, and the expression vector is composed of a preproinsulin sequence that is a fused form of an artificial leader peptide and the native proinsulin. It has been reported that the sequence of the leader peptide affects the production of insulin. To analyze how the leader peptide affects the maturation of insulin structurally, we adapted several in silico simulations using 13 artificial proinsulin sequences. Three-dimensional structures of models were predicted and compared. Although their sequences had few differences, the predicted structures were somewhat different. The structures were refined by molecular dynamics simulation, and the energy of each model was estimated. Then, protein-protein docking between the models and trypsin was carried out to compare how efficiently the protease could access the cleavage sites of the proinsulin models. The results showed some concordance with experimental results that have been reported; so, we expect our analysis will be used to predict the optimized sequence of artificial proinsulin for more effective production.

Sung Hun Jung
Chang-Kyu Kim
Gunhee Lee
Jonghwan Yoon
Minho Lee


Perspectives of International Human Epigenome Consortium

Abstract: As the International Human Epigenome Consortium (IHEC) launched officially at the 2010 Washington meeting, a giant step toward the conquest of unexplored regions of the human genome has begun. IHEC aims at the production of 1,000 reference epigenomes to the international scientific community for next 7-10 years. Seven member institutions, including South Korea, Korea National Institute of Health (KNIH), will produce 25-200 reference epigenomes individually, and the produced data will be publically available by using a data center. Epigenome data will cover from whole genome bisulfite sequencing, histone modification, and chromatin access information to miRNA-seq. The final goal of IHEC is the production of reference maps of human epigenomes for key cellular status relevant to health and disease.


Prevention of tight-junction disruption via enhancement of ROBO4 attenuates influenza-induced blood-brain barrier injury

Abstract: Abstract This study sought to elucidate the protective role of Roundabout 4 (ROBO4) in maintaining blood-brain barrier (BBB) integrity during influenza virus-induced barrier dysfunction. The functional role of ROBO4 was examined using both in vivo and in vitro influenza infection models. Specifically, mechanistic investigations focused on the viral-induced down-regulation of ROBO4 and its subsequent impact on the vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/endothelial nitric oxide synthase (eNOS) signaling axis and key tight junction (TJ) proteins, including Claudin-1, Occludin, and Claudin-5. Additionally, lentiviral-mediated ROBO4 overexpression was utilized to validate its potential protective efficacy. The results showed that influenza virus infection significantly down-regulated ROBO4 expression, which in turn enhanced the interaction between VEGF and its receptor, VEGFR2. Consequently, this molecular event triggered the PI3K/AKT/eNOS signaling cascade, leading to the depletion of TJ proteins and subsequent impairment of BBB integrity. Notably, ROBO4 overexpression effectively inhibited the VEGF-VEGFR2 interaction, suppressed the activation of the PI3K/AKT/eNOS pathway, and restored the expression levels of Claudin-1 and Occludin, thereby preserving barrier function. Overall, by identifying ROBO4 as a critical regulator of BBB integrity, this study highlights its potential as a novel therapeutic target. Furthermore, these findings provide theoretical support for the development of preventative and interventional strategies to mitigate the neurological complications associated with influenza virus infections.

Mei Lu
Ming Yu
Li Feng
Ying Yi
Linsong Hou
Lu Gao
Quangang Xu
Yi Zhang