bluuebunny/crossref_metadata_2025_split huggingface dataset:
The emergence of circadian timekeeping in the intestine
Authors: Parasram Kathyani , Zuccato Amy , Shin Minjeong , Willms Reegan , DeVeale Brian , Foley Edan , Karpowicz Phillip 
Published: February 2024

AbstractThe circadian clock is a molecular timekeeper, present from cyanobacteria to mammals, that coordinates internal physiology with the external environment. The clock has a 24-h period however development proceeds with its own timing, raising the question of how these interact. Using the intestine of Drosophila melanogaster as a model for organ development, we track how and when the circadian clock emerges in specific cell types. We find that the circadian clock begins abruptly in the adult intestine and gradually synchronizes to the environment after intestinal development is complete. This delayed start occurs because individual cells at earlier stages lack the complete circadian clock gene network. As the intestine develops, the circadian clock is first consolidated in intestinal stem cells with changes in Ecdysone and Hnf4 signalling influencing the transcriptional activity of Clk/cyc to drive the expression of tim, Pdp1, and vri. In the mature intestine, stem cell lineage commitment transiently disrupts clock activity in differentiating progeny, mirroring early developmental clock-less transitions. Our data show that clock function and differentiation are incompatible and provide a paradigm for studying circadian clocks in development and stem cell lineages.
Multi-night cortico-basal recordings reveal mechanisms of NREM slow-wave suppression and spontaneous awakenings in Parkinson’s disease
Authors: Anjum Md Fahim , Smyth Clay , Zuzuárregui Rafael , Dijk Derk Jan , Starr Philip A. , Denison Timothy , Little Simon 
Published: February 2024

AbstractSleep disturbance is a prevalent and disabling comorbidity in Parkinson’s disease (PD). We performed multi-night (n = 57) at-home intracranial recordings from electrocorticography and subcortical electrodes using sensing-enabled Deep Brain Stimulation (DBS), paired with portable polysomnography in four PD participants and one with cervical dystonia (clinical trial: NCT03582891). Cortico-basal activity in delta increased and in beta decreased during NREM (N2 + N3) versus wakefulness in PD. DBS caused further elevation in cortical delta and decrease in alpha and low-beta compared to DBS OFF state. Our primary outcome demonstrated an inverse interaction between subcortical beta and cortical slow-wave during NREM. Our secondary outcome revealed subcortical beta increases prior to spontaneous awakenings in PD. We classified NREM vs. wakefulness with high accuracy in both traditional (30 s: 92.6 ± 1.7%) and rapid (5 s: 88.3 ± 2.1%) data epochs of intracranial signals. Our findings elucidate sleep neurophysiology and impacts of DBS on sleep in PD informing adaptive DBS for sleep dysfunction.
Development of pathophysiologically relevant models of sickle cell disease and β-thalassemia for therapeutic studies
Authors: Gupta Pragya , Goswami Sangam Giri , Kumari Geeta , Saravanakumar Vinodh , Bhargava Nupur , Rai Akhila Balakrishna , Singh Praveen , Bhoyar Rahul C. , Arvinden V. R. , Gunda Padma , Jain Suman , Narayana Vanya Kadla , Deolankar Sayali C. , Prasad T. S. Keshava , Natarajan Vivek T. , Scaria Vinod , Singh Shailja , Ramalingam Sivaprakash 
Published: February 2024

AbstractEx vivo cellular system that accurately replicates sickle cell disease and β-thalassemia characteristics is a highly sought-after goal in the field of erythroid biology. In this study, we present the generation of erythroid progenitor lines with sickle cell disease and β-thalassemia mutation using CRISPR/Cas9. The disease cellular models exhibit similar differentiation profiles, globin expression and proteome dynamics as patient-derived hematopoietic stem/progenitor cells. Additionally, these cellular models recapitulate pathological conditions associated with both the diseases. Hydroxyurea and pomalidomide treatment enhanced fetal hemoglobin levels. Notably, we introduce a therapeutic strategy for the above diseases by recapitulating the HPFH3 genotype, which reactivates fetal hemoglobin levels and rescues the disease phenotypes, thus making these lines a valuable platform for studying and developing new therapeutic strategies. Altogether, we demonstrate our disease cellular systems are physiologically relevant and could prove to be indispensable tools for disease modeling, drug screenings and cell and gene therapy-based applications.
Global fungal-host interactome mapping identifies host targets of candidalysin
Authors: Zhang Tian-Yi , Chen Yao-Qi , Tan Jing-Cong , Zhou Jin-An , Chen Wan-Ning , Jiang Tong , Zha Jin-Yin , Zeng Xiang-Kang , Li Bo-Wen , Wei Lu-Qi , Zou Yun , Zhang Lu-Yao , Hong Yue-Mei , Wang Xiu-Li , Zhu Run-Ze , Xu Wan-Xing , Xi Jing , Wang Qin-Qin , Pan Lei , Zhang Jian , Luan Yang , Zhu Rui-Xin , Wang Hui , Chen Changbin , Liu Ning-Ning 
Published: February 2024

AbstractCandidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.
Deep learning infers clinically relevant protein levels and drug response in breast cancer from unannotated pathology images
Authors: Liu Hui , Xie Xiaodong , Wang Bin 
Published: February 2024

AbstractThe computational pathology has been demonstrated to effectively uncover tumor-related genomic alterations and transcriptomic patterns. Although proteomics has indeed shown great potential in the field of precision medicine, few studies have focused on the computational prediction of protein levels from pathology images. In this paper, we assume that deep learning-based pathological features imply the protein levels of tumor biomarkers that are indicative of prognosis and drug response. For this purpose, we propose wsi2rppa, a weakly supervised contrastive learning framework to infer the protein levels of tumor biomarkers from whole slide images (WSIs) in breast cancer. We first conducted contrastive learning-based pre-training on tessellated tiles to extract pathological features, which are then aggregated by attention pooling and adapted to downstream tasks. We conducted extensive evaluation experiments on the TCGA-BRCA cohort (1978 WSIs of 1093 patients with protein levels of 223 biomarkers) and the CPTAC-BRCA cohort (642 WSIs of 134 patients). The results showed that our method achieved state-of-the-art performance in tumor diagnostic tasks, and also performed well in predicting clinically relevant protein levels and drug response. To show the model interpretability, we spatially visualized the WSIs colored the tiles by their attention scores, and found that the regions with high scores were highly consistent with the tumor and necrotic regions annotated by a 10-year experienced pathologist. Moreover, spatial transcriptomic data further verified that the heatmap generated by attention scores agrees greatly with the spatial expression landscape of two typical tumor biomarker genes. In predicting the response to drug trastuzumab treatment, our method achieved a 0.79 AUC value which is much higher than the previous study reported 0.68. These findings showed the remarkable potential of computational pathology in the prediction of clinically relevant protein levels, drug response, and clinical outcomes.
Gait impairment-related axonal degeneration in Parkinson’s disease by neurite orientation dispersion and density imaging
Authors: Wei Xuan , Wang Shiya , Zhang Mingkai , Yan Ying , Wang Zheng , Wei Wei , Tuo Houzhen , Wang Zhenchang 
Published: February 2024

AbstractMicrostructural alterations in the brain networks of Parkinson’s disease (PD) patients are correlated with gait impairments. Evaluate microstructural alterations in the white matter (WM) fiber bundle tracts using neurite orientation dispersion and density imaging (NODDI) technique in PD versus healthy controls (HC). In this study, 24 PD patients and 29 HC were recruited. NODDI and high-resolution 3D structural images were acquired for each participant. The NODDI indicators, including the intracellular neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISO), were compared between the two groups. Diffusion-weighted (DW) images were preprocessed using MRtrix 3.0 software and the orientation distribution function to trace the main nerve fiber tracts in PD patients. Quantitative gait and clinical assessment scales were used to compare the medication “ON” and “OFF” states of PD patients. The NDI, ODI, and ISO values of the WM fiber bundles were significantly higher in PD patients compared to HC. Fiber bundles, including the anterior thalamic radiation, corticospinal tract, superior longitudinal fasciculus, forceps major, cingulum, and inferior longitudinal fasciculus, were found to be significantly affected in PD. The NDI changes of PD patients were well correlated with stride lengths in the “ON” state; ODI changes were correlated with the stride time in the “ON” and “OFF” states and ISO changes were correlated with the stride time and cadence in the “ON” state. In conclusion, combination of NODDI technique and gait parameters can help detect gait impairment in PD patients early and accurately.
ReptTraits: a comprehensive dataset of ecological traits in reptiles
Authors: Oskyrko Oleksandra , Mi Chunrong , Meiri Shai , Du Weiguo 
Published: February 2024

AbstractTrait datasets are increasingly being used in studies investigating eco-evolutionary theory and global conservation initiatives. Reptiles are emerging as a key group for studying these questions because their traits are crucial for understanding the ability of animals to cope with environmental changes and their contributions to ecosystem processes. We collected data from earlier databases, and the primary literature to create an up-to-date dataset of reptilian traits, encompassing 40 traits from 12060 species of reptiles (Archelosauria: Crocodylia and Testudines, Rhynchocephalia, and Squamata: Amphisbaenia, Sauria, and Serpentes). The data were gathered from 1288 sources published between 1820 and 2023. The dataset includes morphological, physiological, behavioral, and life history traits, as well as information on the availability of genetic data, IUCN Red List assessments, and population trends.
Phytochemical variations antioxidant, and antibacterial activities among zebaria sumac (Rhus coriaria var. zebaria) populations in Iraq
Authors: Shahrivari Saba , Zeebaree Saeed Mizgeen Saeed , Alizadeh-Salteh Saeideh , Feizy Hadar S. , Morshedloo Mohammad Reza 
Published: February 2024

AbstractSumac (Rhus coriaria L.) is one of the medicinal plants of Anacardiaceae family and widely used as a spice in Iran and Arab countries. Rhus coriaria var. zebaria is a small tree or large shrub, wildly growing in Iraq and described as a new variety with special characteristics. These increase the importance of studying sumac in these areas. Here, the phytochemical variations and the antibacterial activity of 50 accessions of this variety from five different climatic conditions was evaluated in order to identify the best accession to use and the best area for its cultivation. This is the most comprehensive study on this plant. Essential oil compounds were identified using GC–MS method and according to the results, Z, E-2,13-octadecadien, caryophyllene oxide, 2,4-decadienal, E-caryophyllene and nonanoic acid were among the main compounds. Also, the variety is a rich source of minerals including K, Ca, Mg, Na, P, and N. Sumac fruit extract from Akre Xerds had the highest anthocyanin and the lowest amount was from Kavilca region. The radical scavenging effect of extract from Dostic area in the concentration of 400 µg/mL is closer to the effect of ascorbic acid. The largest inhibition was found in the sumac extracted oil of Xasto Zhere area against S. aureus in compared with penicillin and amoxicillin and enrofloxacin antibiotics.
Robot therapy aids mental health in patients with hematological malignancy during hematopoietic stem cell transplantation in a protective isolation unit
Authors: Yamada Akiko , Akahane Daigo , Takeuchi Shiho , Miyata Kaori , Sato Takako , Gotoh Akihiko 
Published: February 2024

AbstractPatients with hematological malignancy experience physical and psychological pain, such as a sense of isolation and confinement due to intensive chemotherapy in a protective isolation unit (PIU). We examined whether the intervention of a robotic puppy, aibo (manufactured by Sony), could improve patients' mental health as an alternative therapy for pet therapy, which is not feasible in PIU. This study included 21 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) (n = 16) or autologous HSCT (n = 5). The patients were randomly divided into the aibo and control groups. Psychological effects were regularly assessed by measuring the levels of salivary stress hormone chromogranin A (CgA), serum oxytocin, and serum cortisol and the quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) scores. The aibo group demonstrated a significant decrease in CgA level, while the control group showed the opposite trend. In addition, changes in serum oxytocin and cortisol levels indicated that aibo helped reduce stress. There was no significant difference in the QIDS-SR scores between the two groups; however, the psychomotor activity in the aibo group improved significantly. These findings suggest that aibo intervention during a stay in a PIU can improve the mental health of patients with hematological malignancies who have undergone HSCT.
Influence of inclined magnetic field and heat transfer on the peristaltic flow of Rabinowitsch fluid model in an inclined channel
Authors: Elmhedy Y. , Abd-Alla A. M. , Abo-Dahab S. M. , Alharbi F. M. , Abdelhafez M. A. 
Published: February 2024

AbstractThe recent study is focused on discussion of heat transfer and magnetic field results of peristaltic flow of Rabinowitsch fluid model in an Inclined Channel. In this piece of research, peristalsis’s fundamental problem with heat transfer in the presence of a magnetic field is checked. An incompressible Rabinowitsch fluid is present in an inclined channel, which is considered as the reference for this research. The solutions are devised with the assumptions of long wavelength and low Reynolds number approximations. The resulting equations are then solved exactly by implementing various command of MATHEMATICA subject to relevant boundary conditions. Results are discussed for various flow quantities like temperature, velocity, tangential stress, pressure gradient and rise, and friction force. Computational simulations are performed to determine the flow quantities. This investigation goes beyond mere calculations and examines particle motion to gain deeper insights into flow quantities. Furthermore, this investigates how magnetic field and heat transfer parameters influence these peristaltic flow phenomena. The outcomes of important parameters were plotted and scrutinized. There is amultitude of medical implementations derived from the current consideration, such as the depiction of the gastric juice motion in the small intestine when an endoscope is inserted through it.
Markovian noise modelling and parameter extraction framework for quantum devices
Authors: Brand Dean , Sinayskiy Ilya , Petruccione Francesco 
Published: February 2024

AbstractIn recent years, Noisy Intermediate Scale Quantum (NISQ) computers have been widely used as a test bed for quantum dynamics. This work provides a new hardware-agnostic framework for modelling the Markovian noise and dynamics of quantum systems in benchmark procedures used to evaluate device performance. As an accessible example, the application and performance of this framework is demonstrated on IBM Quantum computers. This framework serves to extract multiple calibration parameters simultaneously through a simplified process which is more reliable than previously studied calibration experiments and tomographic procedures. Additionally, this method allows for real-time calibration of several hardware parameters of a quantum computer within a comprehensive procedure, providing quantitative insight into the performance of each device to be accounted for in future quantum circuits. The framework proposed here has the additional benefit of highlighting the consistency among qubit pairs when extracting parameters, which leads to a less computationally expensive calibration process than evaluating the entire device at once.
SlumberNet: deep learning classification of sleep stages using residual neural networks
Authors: Jha Pawan K. , Valekunja Utham K. , Reddy Akhilesh B. 
Published: February 2024

AbstractSleep research is fundamental to understanding health and well-being, as proper sleep is essential for maintaining optimal physiological function. Here we present SlumberNet, a novel deep learning model based on residual network (ResNet) architecture, designed to classify sleep states in mice using electroencephalogram (EEG) and electromyogram (EMG) signals. Our model was trained and tested on data from mice undergoing baseline sleep, sleep deprivation, and recovery sleep, enabling it to handle a wide range of sleep conditions. Employing k-fold cross-validation and data augmentation techniques, SlumberNet achieved high levels of overall performance (accuracy = 97%; F1 score = 96%) in predicting sleep stages and showed robust performance even with a small and diverse training dataset. Comparison of SlumberNet's performance to manual sleep stage classification revealed a significant reduction in analysis time (~ 50 × faster), without sacrificing accuracy. Our study showcases the potential of deep learning to facilitate sleep research by providing a more efficient, accurate, and scalable method for sleep stage classification. Our work with SlumberNet further demonstrates the power of deep learning in mouse sleep research.
Spatial analysis of 10-year predicted risk and incident atherosclerotic cardiovascular disease: the CoLaus cohort
Authors: Jordan Guillaume , Ridder David , Joost Stephane , Vollenweider Peter , Preisig Martin , Marques-Vidal Pedro , Guessous Idris , Vaucher Julien 
Published: February 2024

AbstractWhether cardiovascular risk scores geographically aggregate and inform on spatial development of atherosclerotic cardiovascular diseases (ASCVD) remains unknown. Our aim is to determine the spatial distribution of 10-year predicted cardiovascular risk and ASCVD, and to compare the overlap of the resulting spatial distributions. Using prospective data from the CoLaus|PsyCoLaus cohort study (2003–2021) we computed SCORE2 in participants free from ASCVD. Geographical distributions of predicted risk and events were determined using the Gi* Getis-Ord autocorrelation statistic. 6203 individuals (54% women, mean age 52.5 ± SD 10.7, ASCVD incidence rate 5.7%) were included. We identified clusters of high versus low predicted risk (4%, 6%, respectively) and ASCVD (5%, 5% respectively) at baseline. They persisted at follow-up. Overlap of SCORE2 and ASCVD clusters was marginal. Body-mass index and alcohol consumption explained most of the predicted risk distribution. For ASCVD, high clusters persisted or were reinforced after multivariate adjustment, while low incidence clusters were reduced, multifactorial determinants. Incidence rate of ASCVD was 2.5% higher (IC 95%, 1.4–3.7) in clusters of higher incidence of ASCVD. To develop up-to-date, geographically targeted prevention strategies, there is a need to study novel geographically risk factors affecting ASCVD and to update commonly used prediction models for a population approach.
First detection and genetic characterization of canine bufavirus in domestic dogs, Thailand
Authors: Charoenkul Kamonpan , Thaw Yu Nandi , Phyu Eaint Min , Jairak Waleemas , Nasamran Chanakarn , Chamsai Ekkapat , Chaiyawong Supassama , Amonsin Alongkorn 
Published: February 2024

AbstractCanine bufavirus (CBuV) was reported in domestic dogs worldwide. We conducted a survey of canine bufavirus in domestic dogs in Thailand from September 2016 to October 2022. Rectal swab samples (n = 531) were collected from asymptomatic dogs and dogs with gastroenteritis signs. The samples were tested for CBuV using PCR with specific primers to the VP1/VP2 gene, and 9.42% (50/531) was CBuV positive. Our findings showed that CBuVs could be detected in both symptomatic and healthy dogs. The Thai CBuVs were found in dogs from different age groups, with a significant presence in those under 1 year (12.60%) and dogs aged 1–5 years (7.34%) (p < 0.05), suggesting a high prevalence of Thai CBuVs in dogs under 5 years of age. We performed complete genome sequencing (n = 15) and partial VP1/VP2 sequencing (n = 5) of Thai CBuVs. Genetic and phylogenetic analyses showed that whole genomes of Thai CBuVs were closely related to Chinese and Italian CBuVs, suggesting the possible origin of Thai CBuVs. The analysis of VP1 and VP2 genes in Thai CBuVs showed that 18 of them were placed in subgroup A, while only 2 belonged to subgroup B. This study is the first to report the detection and genetic characterization of CBuVs in domestic dogs in Thailand. Additionally, surveillance and genetic characterization of CBuVs in domestic animals should be further investigated on a larger scale to elucidate the dynamic, evolution, and distribution of CBuVs.