bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning insights into thrombo-ischemic risks and bleeding events through platelet lysophospholipids and acylcarnitine species
Authors: Harm Tobias , Fu Xiaoqing , Frey Moritz , Dittrich Kristina , Brun Adrian , Castor Tatsiana , Borst Oliver , Müller Karin Anne Lydia , Geisler Tobias , Rath Dominik , Lämmerhofer Michael , Gawaz Meinrad Paul
Published: March 2024

Coronary artery disease (CAD) often leads to adverse events resulting in significant disease burdens. Underlying risk factors often remain inapparent prior to disease incidence and the cardiovascular (CV) risk is not exclusively explained by traditional risk factors. Platelets inherently promote atheroprogression and enhanced platelet functions and distinct platelet lipid species are associated with disease severity in patients with CAD. Lipidomics data were acquired using mass spectrometry and processed alongside clinical data applying machine learning to model estimates of an increased CV risk in a consecutive CAD cohort (n = 595). By training machine learning models on CV risk measurements, stratification of CAD patients resulted in a phenotyping of risk groups. We found that distinct platelet lipids are associated with an increased CV or bleeding risk and independently predict adverse events. Notably, the addition of platelet lipids to conventional risk factors resulted in an increased diagnostic accuracy of patients with adverse CV events. Thus, patients with aberrant platelet lipid signatures and platelet functions are at elevated risk to develop adverse CV events. Machine learning combining platelet lipidome data and common clinical parameters demonstrated an increased diagnostic value in patients with CAD and might improve early risk discrimination and classification for CV events.
Exploring the impact of stress on the electronic structure and optical properties of graphdiyne nanoribbons for advanced optoelectronic applications
Authors: Liu Qiaohan , Feng Naixing , Zou Yi , Fan Chuanqiang , Wang Jingang
Published: March 2024

Graphdiyne (GDY), a two-dimensional carbon material with sp- and sp2-hybridization, is recognized for its unique electronic properties and well-dispersed porosity. Its versatility has led to its use in a variety of applications. The precise control of this material's properties is paramount for its effective utilization in nano-optical devices. One effective method of regulation, which circumvents the need for additional disturbances, involves the application of external stress. This technique provides a direct means of eliciting changes in the electronic characteristics of the material. For instance, when subjected to uniaxial stress, electron transfer occurs at the triple bond. This results in an armchair-edged graphdiyne nanoribbon (A(3)-GDYNR) with a planar width of 2.07 nm, which exhibits a subtle plasmon effect at 500 nm. Conversely, a zigzag-edged graphdiyne nanoribbon (Z(3)-GDYNR) with a planar width of 2.86 nm demonstrates a pronounced plasmon effect within the 250–1200 nm range. This finding suggests that the zigzag nanoribbon surpasses the armchair nanoribbon in terms of its plasmon effect. First principles calculations and ab initio molecular dynamics further confirmed that under applied stress Z(3)-GDYNR exhibits less deformation than A(3)-GDYNR, indicating superior stability. This work provides the necessary theoretical basis for understanding graphene nanoribbons (GDYNRs).
Multi-scale geometric network analysis identifies melanoma immunotherapy response gene modules
Authors: Murgas Kevin A. , Elkin Rena , Riaz Nadeem , Saucan Emil , Deasy Joseph O. , Tannenbaum Allen R.
Published: March 2024

Melanoma response to immune-modulating therapy remains incompletely characterized at the molecular level. In this study, we assess melanoma immunotherapy response using a multi-scale network approach to identify gene modules with coordinated gene expression in response to treatment. Using gene expression data of melanoma before and after treatment with nivolumab, we modeled gene expression changes in a correlation network and measured a key network geometric property, dynamic Ollivier-Ricci curvature, to distinguish critical edges within the network and reveal multi-scale treatment-response gene communities. Analysis identified six distinct gene modules corresponding to sets of genes interacting in response to immunotherapy. One module alone, overlapping with the nuclear factor kappa-B pathway (NFkB), was associated with improved patient survival and a positive clinical response to immunotherapy. This analysis demonstrates the usefulness of dynamic Ollivier-Ricci curvature as a general method for identifying information-sharing gene modules in cancer.
Obstetric infections and clinical characteristics of maternal sepsis: a hospital-based retrospective cohort study
Authors: Kvalvik Sedina Atic , Zakariassen Sofie Branæs , Overrein Sofie , Rasmussen Svein , Skrede Steinar , Baghestan Elham
Published: March 2024

Sepsis is responsible for 50% of intrahospital maternal deaths worldwide. Incidence is increasing in both low and middle-, and high-income countries. There is little data on incidence and clinical outcomes of obstetric infections including maternal sepsis in the Nordic countries. The aims of this study are to give estimates of the occurrence of obstetric infections and maternal sepsis in a Norwegian hospital cohort, assess the quality of management of maternal sepsis cases, and evaluate the usefulness of diagnostic codes to identify maternal sepsis retrospectively. We conducted a retrospective cohort study of pregnant, labouring, post-abortion, and postpartum women. We assessed the accuracy of the diagnostic code most frequently applied for maternal sepsis, O85. We found 7.8% (95% confidence interval 7.1–8.5) infection amongst pregnant, labouring, and postpartum women. The incidence of maternal sepsis was 0.3% (95% confidence interval 0.2–0.5), and the majority of sepsis cases were recorded in the postpartum period. Two thirds of women were given broad-spectrum antibiotics at the time sepsis was diagnosed, but only 15.4% of women with puerperal sepsis were given antimicrobials in accordance with national guidelines. When used retrospectively, obstetric infection codes are insufficient in identifying both maternal and puerperal sepsis, with only 20.3% positive predictive value for both conditions. In conclusion, obstetric infections contribute significantly to maternal morbidity in Norway’s second largest maternity hospital. This study provides incidences of maternal infections for hospitalised patients in temporal relation to pregnancy, labour, abortion and the postpartum period, knowledge which is valuable for planning of health care services and allocation of resources. In addition, the study highlights areas where improvement is needed in clinical handling of maternal sepsis. There is need for studies on the management quality and use of correct diagnostic codes in this patient category.
Optimal duration and timing of basic-life-support-only intervention for patients with out-of-hospital cardiac arrest
Authors: Takei Yutaka , Toyama Gen , Takahashi Tsukasa , Omatsu Kentaro
Published: March 2024

To elucidate the relationship between the interval from cardiopulmonary resuscitation initiation to return of spontaneous circulation (ROSC) and neurologically favourable 1-month survival in order to determine the appropriate duration of basic life support (BLS) without advanced interventions. This population-based cohort study included patients aged ≥ 18 years with 9132 out-of-hospital cardiac arrest of presumed cardiac origin who were bystander-witnessed and had achieved ROSC between 2018 and 2020. Patients were classified into two groups based on the resuscitation methods as the “BLS-only” and the “BLS with administered epinephrine (BLS-AE)” groups. Receiver operating characteristic (ROC) curve analysis indicated that administering BLS for 9 min yielded the best neurologically outcome for patients with a shockable rhythm [sensitivity, 0.42; specificity, 0.27; area under the ROC curve (AUC), 0.60] in the BLS-only group. Contrastingly, for patients with a non-shockable rhythm, performing BLS for 6 min yielded the best neurologically outcome (sensitivity, 0.65; specificity, 0.43; AUC, 0.63). After propensity score matching, multivariate analysis revealed that BLS-only resuscitation [6.44 (5.34–7.77)] was associated with neurologically favourable 1-month survival. This retrospective study revealed that BLS-only intervention had a significant impact in the initial minutes following CPR initiation. Nevertheless, its effectiveness markedly declined thereafter. The optimal duration for effective BLS-only intervention varied depending on the patient's initial rhythm. Consequently, advanced interventions should be administered within the first few minutes to counteract the diminishing effectiveness of BLS-only intervention.
Predicting early Alzheimer’s with blood biomarkers and clinical features
Authors: AlMansoori Muaath Ebrahim , Jemimah Sherlyn , Abuhantash Ferial , AlShehhi Aamna
Published: March 2024

Alzheimer’s disease (AD) is an incurable neurodegenerative disorder that leads to dementia. This study employs explainable machine learning models to detect dementia cases using blood gene expression, single nucleotide polymorphisms (SNPs), and clinical data from Alzheimer’s Disease Neuroimaging Initiative (ADNI). Analyzing 623 ADNI participants, we found that the Support Vector Machine classifier with Mutual Information (MI) feature selection, trained on all three data modalities, achieved exceptional performance (accuracy = 0.95, AUC = 0.94). When using gene expression and SNP data separately, we achieved very good performance (AUC = 0.65, AUC = 0.63, respectively). Using SHapley Additive exPlanations (SHAP), we identified significant features, potentially serving as AD biomarkers. Notably, genetic-based biomarkers linked to axon myelination and synaptic vesicle membrane formation could aid early AD detection. In summary, this genetic-based biomarker approach, integrating machine learning and SHAP, shows promise for precise AD diagnosis, biomarker discovery, and offers novel insights for understanding and treating the disease. This approach addresses the challenges of accurate AD diagnosis, which is crucial given the complexities associated with the disease and the need for non-invasive diagnostic methods.
Long-term, non-invasive FTIR detection of low-dose ionizing radiation exposure
Authors: Inman Jamie L. , Wu Yulun , Chen Liang , Brydon Ella , Ghosh Dhruba , Wan Kenneth H. , De Chant Jared , Obst-Huebl Lieselotte , Nakamura Kei , Ralston Corie Y. , Celniker Susan E. , Mao Jian-Hua , Zwart Peter H. , Holman Hoi-Ying N. , Chang Hang , Brown James B. , Snijders Antoine M.
Published: March 2024

Non-invasive methods of detecting radiation exposure show promise to improve upon current approaches to biological dosimetry in ease, speed, and accuracy. Here we developed a pipeline that employs Fourier transform infrared (FTIR) spectroscopy in the mid-infrared spectrum to identify a signature of low dose ionizing radiation exposure in mouse ear pinnae over time. Mice exposed to 0.1 to 2 Gy total body irradiation were repeatedly measured by FTIR at the stratum corneum of the ear pinnae. We found significant discriminative power for all doses and time-points out to 90 days after exposure. Classification accuracy was maximized when testing 14 days after exposure (specificity > 0.9 with a sensitivity threshold of 0.9) and dropped by roughly 30% sensitivity at 90 days. Infrared frequencies point towards biological changes in DNA conformation, lipid oxidation and accumulation and shifts in protein secondary structure. Since only hundreds of samples were used to learn the highly discriminative signature, developing human-relevant diagnostic capabilities is likely feasible and this non-invasive procedure points toward rapid, non-invasive, and reagent-free biodosimetry applications at population scales.
Application of analysis of variance to determine important features of signals for diagnostic classifiers of displacement pumps
Authors: Konieczny Jarosław , Łatas Waldemar , Stojek Jerzy
Published: March 2024

This paper presents the use of one-way analysis of variance ANOVA as an effective tool for ranking the features calculated from diagnostic signals and evaluates their impact on the accuracy of the machine learning system's classification of displacement pump wear.The first part includes a review of contemporary diagnostic systems and a description of typical damage of multi-piston displacement pumps and Its causes. The work also contains description of a diagnostic experiment which was conducted in order to obtain the matrix of vibration signals and the matrix of pressures measured at selected locations on the pump housing and at the pump pressure line. The measured signals were subjected to time–frequency analysis. The features of signals calculated in the time and frequency domains were ranked using the ANOVA. The next step involved the use the available classifiers in pump wear evaluation, conducting tests and assessing their effectiveness in terms of the ranking of features and the origin of diagnostic signals.
Symmetric projection optimizer: concise and efficient solving engineering problems using the fundamental wave of the Fourier series
Authors: Su Haoxiang , Dong Zhenghong , Liu Yi , Mu Yao , Li Sen , Xia Lurui
Published: March 2024

The fitness function value is a kind of important information in the search process, which can be more targeted according to the guidance of the fitness function value. Most existing meta-heuristic algorithms only use the fitness function value as an indicator to compare the current variables as good or bad but do not use the fitness function value in the search process. To address this problem, the mathematical idea of the fitting is introduced into the meta-heuristic algorithm, and a symmetric projection optimizer (SPO) is proposed to solve numerical optimization and engineering problems more efficiently. The SPO algorithm mainly utilizes a new search mechanism, the symmetric projection search (SP) method. The SP method quickly completes the fitting of the projection plane, which is located through the symmetry of the two points and finds the minima in the projection plane according to the fitting result. Fitting by using the fitness function values allows the SP to find regions where extreme values may exist more quickly. Based on the SP method, exploration and exploitation strategies are constructed, respectively. The exploration strategy is used to find better regions, and the exploitation strategy is used to optimize the discovered regions continuously. The timing of the use of the two strategies is designed so that the SPO algorithm can converge faster while avoiding falling into local optima. The effectiveness of the SPO algorithm is extensively evaluated using seven test suites, including CEC2017, CEC2019, CEC2020, and CEC2022. It is also compared with two sets of 19 recent competitive algorithms. Statistical analyses are performed using five metrics such as the Wilcoxon test, the Friedman test, and variance. Finally, the practicality of the SPO algorithm is verified by four typical engineering problems and a real spacecraft trajectory optimization problem. The results show that the SPO algorithm can find superior results in 94.6% of the comparison tests and is a promising alternative for solving real-world problems.
First use of silicon carbide detectors with graphene-enhanced contacts for medical dosimetry
Authors: Lopez Paz Ivan , Fleta Celeste , Gomez Faustino , González Diego Miguel , Pellegrini Giulio
Published: March 2024

Silicon Carbide (SiC) is a radiation hard wide bandgap semiconductor, which makes it an interesting alternative for radiation detector fabrication, with potential applications such as High Energy Physics, synchrotron and radiotherapy instrumentation. In addition, by reducing the amount of metal over the active area of said detectors (typically used for electrical connectivity with the implant of the pn-junction) unwanted effects from secondary interactions which can affect the accuracy of the measurement can be diminished, essential to meet the medical standards of precision. In this article, the use of epitaxially-grown graphene is explored as an alternative to metallic contacts with these prototypes. To this end, the first prototypes of SiC diodes with epitaxial graphene contacts were produced at IMB-CNM for radiation detection,along with reference devices. In order to characterise the feasibility of the technology in the medical application, the dose rate linearity of the SiC device with graphene was measured in a radiotherapy Linac in the dose rate range of 1–6 Gy/min. The response of the device was compared to that observed on devices with similar geometries reported elsewhere. To fully characterise the devices, the same exercise was repeated in a laboratory X-ray tube. Under the later set-up, the prototype is compared against a device with a fully metallised active region.
Immunoinformatics and computational approaches driven designing a novel vaccine candidate against Powassan virus
Authors: Nguyen Truc Ly , Kim Heebal
Published: March 2024

Powassan virus (POWV) is an arthropod-borne virus (arbovirus) capable of causing severe illness in humans for severe neurological complications, and its incidence has been on the rise in recent years due to climate change, posing a growing public health concern. Currently, no vaccines to prevent or medicines to treat POWV disease, emphasizing the urgent need for effective countermeasures. In this study, we utilize bioinformatics approaches to target proteins of POWV, including the capsid, envelope, and membrane proteins, to predict diverse B-cell and T-cell epitopes. These epitopes underwent screening for critical properties such as antigenicity, allergenicity, toxicity, and cytokine induction potential. Eight selected epitopes were then conjugated with adjuvants using various linkers, resulting in designing of a potentially stable and immunogenic vaccine candidate against POWV. Moreover, molecular docking, molecular dynamics simulations, and immune simulations revealed a stable interaction pattern with the immune receptor, suggesting the vaccine's potential to induce robust immune responses. In conclusion, our study provided a set of derived epitopes from POWV’s proteins, demonstrating the potential for a novel vaccine candidate against POWV. Further in vitro and in vivo studies are warranted to advance our efforts and move closer to the goal of combatting POWV and related arbovirus infections.
Divergent bacterial landscapes: unraveling geographically driven microbiomes in Atlantic cod
Authors: Fronton Fanny , Villemur Richard , Robert Dominique , St-Pierre Yves
Published: March 2024

Establishing microbiome signatures is now recognized as a critical step toward identifying genetic and environmental factors shaping animal-associated microbiomes and informing the health status of a given host. In the present work, we prospectively collected 63 blood samples of the Atlantic cod population of the Southern Gulf of Saint Lawrence (GSL) and characterized their 16S rRNA circulating microbiome signature. Our results revealed that the blood microbiome signature was dominated at the phylum level by Proteobacteria, Bacteroidetes, Acidobacteria and Actinobacteria, a typical signature for fish populations inhabiting the GSL and other marine ecosystems. At the genus level, however, we identified two distinct cod groups. While the microbiome signature of the first group was dominated by Pseudoalteromonas, a genus we previously found in the microbiome signature of Greenland and Atlantic halibut populations of the GSL, the second group had a microbiome signature dominated by Nitrobacter and Sediminibacterium (approximately 75% of the circulating microbiome). Cods harboring a Nitrobacter/Sediminibacterium-rich microbiome signature were localized in the most southern part of the GSL, just along the northern coast of Cape Breton Island. Atlantic cod microbiome signatures did not correlate with the weight, length, relative condition, depth, temperature, sex, and salinity, as previously observed in the halibut populations. Our study provides, for the first time, a unique snapshot of the circulating microbiome signature of Atlantic cod populations and the potential existence of dysbiotic signatures associated with the geographical distribution of the population, probably linked with the presence of nitrite in the environment.
Space dynamic target tracking method based on five-frame difference and Deepsort
Authors: Huang Cheng , Zeng Quanli , Xiong Fangyu , Xu Jiazhong
Published: March 2024

For the problem of space dynamic target tracking with occlusion, this paper proposes an online tracking method based on the combination between the five-frame difference and Deepsort (Simple Online and Realtime Tracking with a Deep Association Metric), which is to achieve the identification first and then tracking of the dynamic target. First of all, according to three-frame difference, the five-frame difference is improved, and through the integration with ViBe (Visual Background Extraction), the accuracy and anti-interference ability are enhanced; Secondly, the YOLOv5s (You Look Only Once) is improved using preprocessing of DWT (Discrete Wavelet Transformation) and injecting GAM (Global Attention Module), which is considered as the detector for Deepsort to solve the missing in occlusion, and the real-time and accuracy can be strengthened; Lastly, simulation results show that the proposed space dynamic target tracking can keep stable to track all dynamic targets under the background interference and occlusion, the tracking precision is improved to 93.88%. Furthermore, there is a combination with the physical depth camera D435i, experiments on target dynamics show the effectiveness and superiority of the proposed recognition and tracking algorithm in the face of strong light and occlusion.
A risk prediction nomogram for resistant hypertension in patients with obstructive sleep apnea
Authors: Lin Hongze , Zhou Chen , Li Jiaying , Ma Xiuqin , Yang Yan , Zhu Taofeng
Published: March 2024

Patients with obstructive sleep apnea (OSA) are liable to have resistant hypertension (RH) associated with unfavorable cardiovascular events. It is of necessity to predict OSA patients who are susceptible to resistant hypertension. Hence, we conducted a retrospective study based on the clinical records of OSA patients admitted to Yixing Hospital Affiliated to Jiangsu University from January 2018 to December 2022. According to different time periods, patients diagnosed between January 2018 and December 2021 were included in the training set (n = 539) for modeling, and those diagnosed between January 2022 and December 2022 were enrolled into the validation set (n = 259) for further assessment. The incidence of RH in the training set and external validation set was comparable (P = 0.396). The related clinical data of patients enrolled were collected and analyzed through univariate analysis and least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a nomogram. Finally, five variables were confirmed as independent risk factors for OSA patients with RH, including smoking, heart disease, neck circumference, AHI and T90. The nomogram established on the basis of variables above was shown to have good discrimination and calibration in both the training set and validation set. Decision curve analysis indicated that the nomogram was useful for a majority of OSA patients. Therefore, our nomogram might be useful to identify OSA patients at high risk of developing RH and facilitate the individualized management of OSA patients in clinical practice.
Response of upper tropospheric water vapor to global warming and ENSO
Authors: Li Li , Chen Zhiping , Wang Bingkun , Fan Jiao , Lu Tieding , Lv Kaiyun
Published: March 2024

The upper tropospheric water vapor is a key component of Earth's climate. Understanding variations in upper tropospheric water vapor and identifying its influencing factors is crucial for enhancing our comprehension of global climate change. While many studies have shown the impact of El Niño-Southern Oscillation (ENSO) and global warming on water vapor, how they affect the upper tropospheric water vapor remains unclear. Long-term, high-precision ERA5 specific humidity data from the European Centre for Medium-Range Weather Forecasts (ECMWF) provided the data foundation for this study. On this basis, we successfully obtained the patterns of global warming (Independent Component 1, IC1) and ENSO (Independent Component 2, IC2) by employing the strategy of independent component analysis (ICA) combined with non-parametric optimal dimension selection to investigate the upper tropospheric water vapor variations and responses to ENSO and global warming. The results indicate that global warming and ENSO are the primary factors contributing to water vapor variations in the upper troposphere, achieving the significant correlations of 0.87 and 0.61 with water vapor anomalies respectively. Together, they account for 86% of the global interannual variations in water vapor. Consistent with previous studies, our findings also find positive anomalies in upper tropospheric water vapor during El Niño years and negative anomalies during La Niña years. Moreover, the influence extent of ENSO on upper tropospheric water vapor varies with the changing seasons.
The effects of green and chemically-synthesized copper oxide nanoparticles on the production and gene expression of morphinan alkaloids in Oriental poppy
Authors: khaldari Iman , Naghavi Mohammad Reza , Motamedi Elaheh , Zargar Meisam
Published: March 2024

Oriental poppy (Papaver orientale L.) belonging to the Papaveraceae family, has the capacity to synthesize a wide range of benzylisoquinoline alkaloids (BIAs). This experiment was conducted to investigate the effects of green and chemical copper oxide nanoparticles (CuO NPs) elicitors on oxidative stress and the BIAs biosynthesis pathway in the cell suspension culture of P. orientale. This research shows that both green and chemical CuO NPs at concentrations of 20 mg/L and 40 mg/L, induce oxidative stress in the cell suspension of P. orientale by increasing the production of H2O2 and the activity of antioxidant enzymes. The comparison of treatments revealed that utilizing a lower concentration of CuO NPs (20 mg/L) and extending the duration of cell suspension incubation (up to 48 h) play a more influential role in inducing the expression of the BIAs biosynthesis pathway genes (PsWRKY, TYDC, SalSyn, SalR, SalAT, T6ODM, COR and CODM) and increasing the production of morphinan alkaloids (thebaine, codeine, and morphine). The overarching results indicate that the concentration of CuO NPs and the duration of cell treatment have a more significant impact than the nature of CuO NPs in inducing oxidative stress and stimulating the expression of the BIAs pathway genes.
Therapeutic effect and study of human umbilical cord blood mononuclear cells in patients with ischaemic bowel disease
Authors: Cai Xiaoxiao , Li Yonghao , Gao Fengyu , Muhammad Bilal , Yang Hongli
Published: March 2024

Ischaemic bowel disease (ICBD) is a group of intestinal ischaemia syndromes caused by various aetiologies of reduced intestinal blood flow or vascular occlusion. ICBD can present as abdominal pain, bloody stool, and diarrhoea. This disease often occurs in middle-aged and elderly individuals with cardiovascular and cerebrovascular diseases. The incidence of ischaemic bowel disease has been increasing for decades, and it is difficult to diagnose, resulting in rapid disease progression and a high mortality rate. Therefore, fully understanding this disease, improving the diagnosis rate of this disease, and finding appropriate treatment methods are urgently needed to improve the condition and prognosis of patients. Umbilical cord blood stem cells are accessible, have weak immunogenicity, and have various biological functions, such as angiogenesis, inflammation and immune regulation. Many studies have confirmed that cord blood stem cells can relieve ischaemia, and these cells have attracted tremendous amounts of attention in regenerative medicine in recent years. In this paper, we discuss the clinical characteristics of ICBD, analyse the characteristics of human umbilical cord blood mononuclear cells (HUCB-MNCs), and use its to treat ischaemic bowel disease. Additionally, we compare the clinical manifestations and related indicators before and after treatment to evaluate the efficacy and safety of these methods.
Effect of digital ocular massage on intraocular pressure and Schlemm’s canal dimensions
Authors: Wu Tiffany H. Y. , Lau Henry K. C. , Lai Carmelo H. Y. , Wong Ruby W. L. , Wong Antonia K. W. , Lam Andrew Kwok-cheung
Published: March 2024

Digital ocular massage has been reported to temporarily lower intraocular pressure (IOP). This could be related to an enhanced aqueous humor outflow; however, the mechanism is not clearly understood. Using anterior segment optical coherence tomography, the Schlemm’s canal (SC) and trabecular meshwork (TM) can be imaged and measured. Here, 66 healthy adults underwent digital ocular massage for 10 min in their right eyes. The IOP and dimensions of the SC and TM were measured before and after ocular massage. All subjects demonstrated IOP reduction from 15.7 ± 2.5 mmHg at baseline to 9.6 ± 2.2 mmHg immediately after, and median of 11.6 mmHg 5-min after ocular massage (Friedman’s test, p < 0.001). There was significant change in SC area (median 10,063.5 μm2 at baseline to median 10,151.0 μm2 after ocular massage, Wilcoxon test, p = 0.02), and TM thickness (median 149.8 μm at baseline to 144.6 ± 25.3 μm after ocular massage, Wilcoxon test, p = 0.036). One-third of the subjects demonstrated collapse of the SC area (−2 to −52%), while two-thirds showed expansion of the SC area (2 to 168%). There were no significant changes in SC diameter (270.4 ± 84.1 μm vs. 276.5 ± 68.7 μm, paired t-test, p = 0.499), and TM width (733.3 ± 110.1 μm vs. 733.5 ± 111.6 μm, paired t-test, p = 0.988). Eyes with a higher baseline IOP demonstrated a greater IOP reduction (Pearson correlation coefficient r = −0.521, p < 0.001). Eyes with smaller SC area at baseline showed greater SC area expansion (Pearson correlation coefficient = −0.389, p < 0.001). Greater IOP reduction appeared in eyes with greater SC area expansion (Pearson correlation coefficient r = −0.306, p = 0.01). Association between change in IOP and change in TM thickness was not significant (Spearman’s ρ = 0.015, p = 0.902). Simple digital ocular massage is an effective method to lower IOP values, and change in the SC area was significantly associated with IOP changes.
Exploring the anatomical configurations of the cerebral arteries in a cohort of South African patients
Authors: Sibiya Gugulethu , Omotoso Bukola R. , Harrichandparsad Rohen , Lazarus Lelika
Published: March 2024

The cerebral arteries, specifically the anterior cerebral artery (ACA) and posterior cerebral artery (PCA), work together with the smaller calibre arteries to provide effective communication between the anterior and posterior circuits of the brain via the circle of Willis (CoW). Morphologic variations of the cerebral arteries and the CoW may alter blood flow to the brain, resulting in intracranial vascular disorders associated with stroke, and aneurysms. This study aimed to document the morphology of the cerebral arteries and the CoW in the South African population. Two hundred and thirty-nine computed tomography angiography scans were assessed. Cerebral arteries and CoW normal morphology and variations were classified as complete, absent, or hypoplastic. The ACA A1 was absent in 4.91%, hypoplastic in 30.40%, fenestrated in 1.06%, and typical in 63.6%. The ACA A2 was absent in 0.42%, hypoplastic in 26.28%, and typical in 69.44%. We found triple ACA A2 in 2.98%, azygos in 1.28% and fenestrated in 1.28%. The middle cerebral artery (MCA) was hypoplastic in 7.35% and typical in 92.64%. The PCA was hypoplastic in 28.74% and typical in 71.25%. Knowledge of the configuration of the CoW plays a significant role in guiding therapeutic decision-making in treating various neurovascular pathologies.
Predictive modeling of burnout based on organizational culture perceptions among health systems employees: a comparative study using correlation, decision tree, and Bayesian analyses
Authors: Johnson Teray , Shamroukh Sameh
Published: March 2024

Burnout is a significant concern, particularly within the healthcare field, affecting both nurses and physicians. It is a common issue in health systems, which encompass a range of healthcare facilities, such as hospitals, physician practices, ambulatory sites, and administrative offices like finance. Despite this, there has not been an extensive exploration of burnout in employees working directly with patients versus those in non-patient-facing roles within these health systems. It is important to note that organizational culture plays a crucial role in influencing various aspects of employees' work-life balance and their experiences of burnout. This study adopts a cross-sectional design, involving the distribution of a 57-question Likert scale survey to employees in health systems. These employees serve in various roles, both patient-facing and non-patient-facing, within jointly owned healthcare organizations, which encompass hospitals, ambulatory sites, and administrative offices. The survey was disseminated through trade organizations and employees at the managerial level and above within these health systems. Data was collected between October 2022 and January 2023, resulting in a total of 67 responses. The study employs correlation analysis to explore the connection between organizational culture and burnout. Furthermore, a decision tree model is constructed to predict burnout scores based on survey responses, specifically the question regarding the perceived positivity of the organizational culture. The decision tree models indicate that perceiving organizational culture as positive, safety-oriented, and supportive predicts various outcomes for individuals, including job retention, positive experiences with patients, increased callousness, and stimulation while working with colleagues. Bayesian analysis, considering the small sample size, reinforces these findings and provides a different perspective, incorporating prior knowledge and credible intervals. An association test suggests a strong link between a positive organizational culture and burnout symptoms, while another test supports a connection with engagement signs. Similar to nurses and physicians, administrative health systems’ personnel are susceptible to burnout. Organizational culture can affect burnout. Therefore, health systems’ leaders should cultivate an organizational culture that protects against burnout.
MKRN1 regulates the expression profiles and transcription factor activity in HeLa cells inhibition suppresses cervical cancer cell progression
Authors: Dong Xiang , Zhan Yuling , Li Suwan , Yang Minghui , Gao Yu
Published: March 2024

Cervical cancer is one of the most common gynecologic malignancies worldwide, necessitating the identification of novel biomarkers and therapeutic targets. This study aimed to investigate the significance of MKRN1 in cervical cancer and explore its potential as a diagnostic marker and therapeutic target. The results indicated that MKRN1 expression was up-regulated in cervical cancer tissues and correlated with advanced tumor stage, higher grade, and poor patient survival. Functional studies demonstrated that targeting MKRN1 effectively inhibited cell proliferation, migration, and invasion, highlighting its critical role in tumor progression and metastasis. Moreover, the knockdown of MKRN1 resulted in altered expression patterns of six transcription factor-encoding genes, revealing its involvement in gene regulation. Co-expression network analysis unveiled complex regulatory mechanisms underlying the effects of MKRN1 knockdown on gene expression. Furthermore, the results suggested that MKRN1 might serve as a diagnostic marker for personalized treatment strategies and a therapeutic target to inhibit tumor growth, metastasis, and overcome drug resistance. The development of MKRN1-targeted interventions might hold promise for advancing personalized medicine approaches in cervical cancer treatment. Further research is warranted to validate these findings, elucidate underlying mechanisms, and translate these insights into improved management and outcomes for cervical cancer patients.
Regional impacts of warming on biodiversity and biomass in high latitude stream ecosystems across the Northern Hemisphere
Authors: Jackson Michelle C. , Friberg Nikolai , Moliner Cachazo Luis , Clark David R. , Mutinova Petra Thea , O’Gorman Eoin J. , Kordas Rebecca L. , Gallo Bruno , Pichler Doris E. , Bespalaya Yulia , Aksenova Olga V. , Milner Alexander , Brooks Stephen J. , Dunn Nicholas , Lee K.W.K. , Ólafsson Jón S. , Gíslason Gísli M. , Millan Lucia , Bell Thomas , Dumbrell Alex J. , Woodward Guy
Published: March 2024

Warming can have profound impacts on ecological communities. However, explorations of how differences in biogeography and productivity might reshape the effect of warming have been limited to theoretical or proxy-based approaches: for instance, studies of latitudinal temperature gradients are often conflated with other drivers (e.g., species richness). Here, we overcome these limitations by using local geothermal temperature gradients across multiple high-latitude stream ecosystems. Each suite of streams (6-11 warmed by 1-15°C above ambient) is set within one of five regions (37 streams total); because the heating comes from the bedrock and is not confounded by changes in chemistry, we can isolate the effect of temperature. We found a negative overall relationship between diatom and invertebrate species richness and temperature, but the strength of the relationship varied regionally, declining more strongly in regions with low terrestrial productivity. Total invertebrate biomass increased with temperature in all regions. The latter pattern combined with the former suggests that the increased biomass of tolerant species might compensate for the loss of sensitive species. Our results show that the impact of warming can be dependent on regional conditions, demonstrating that local variation should be included in future climate projections rather than simply assuming universal relationships.
Classification of likely functional class for ligand binding sites identified from fragment screening
Authors: Utgés Javier S. , MacGowan Stuart A. , Ives Callum M. , Barton Geoffrey J.
Published: March 2024

Fragment screening is used to identify binding sites and leads in drug discovery, but it is often unclear which binding sites are functionally important. Here, data from 37 experiments, and 1309 protein structures binding to 1601 ligands were analysed. A method to group ligands by binding sites is introduced and sites clustered according to profiles of relative solvent accessibility. This identified 293 unique ligand binding sites, grouped into four clusters (C1-4). C1 includes larger, buried, conserved, and population missense-depleted sites, enriched in known functional sites. C4 comprises smaller, accessible, divergent, missense-enriched sites, depleted in functional sites. A site in C1 is 28 times more likely to be functional than one in C4. Seventeen sites, which to the best of our knowledge are novel, in 13 proteins are identified as likely to be functionally important with examples from human tenascin and 5-aminolevulinate synthase highlighted. A multi-layer perceptron, and K-nearest neighbours model are presented to predict cluster labels for ligand binding sites with an accuracy of 96% and 100%, respectively, so allowing functional classification of sites for proteins not in this set. Our findings will be of interest to those studying protein-ligand interactions and developing new drugs or function modulators.
A platform-independent AI tumor lineage and site (ATLAS) classifier
Authors: Rydzewski Nicholas R. , Shi Yue , Li Chenxuan , Chrostek Matthew R. , Bakhtiar Hamza , Helzer Kyle T. , Bootsma Matthew L. , Berg Tracy J. , Harari Paul M. , Floberg John M. , Blitzer Grace C. , Kosoff David , Taylor Amy K. , Sharifi Marina N. , Yu Menggang , Lang Joshua M. , Patel Krishnan R. , Citrin Deborah E. , Sundling Kaitlin E. , Zhao Shuang G.
Published: March 2024

Histopathologic diagnosis and classification of cancer plays a critical role in guiding treatment. Advances in next-generation sequencing have ushered in new complementary molecular frameworks. However, existing approaches do not independently assess both site-of-origin (e.g. prostate) and lineage (e.g. adenocarcinoma) and have minimal validation in metastatic disease, where classification is more difficult. Utilizing gradient-boosted machine learning, we developed ATLAS, a pair of separate AI Tumor Lineage and Site-of-origin models from RNA expression data on 8249 tumor samples. We assessed performance independently in 10,376 total tumor samples, including 1490 metastatic samples, achieving an accuracy of 91.4% for cancer site-of-origin and 97.1% for cancer lineage. High confidence predictions (encompassing the majority of cases) were accurate 98–99% of the time in both localized and remarkably even in metastatic samples. We also identified emergent properties of our lineage scores for tumor types on which the model was never trained (zero-shot learning). Adenocarcinoma/sarcoma lineage scores differentiated epithelioid from biphasic/sarcomatoid mesothelioma. Also, predicted lineage de-differentiation identified neuroendocrine/small cell tumors and was associated with poor outcomes across tumor types. Our platform-independent single-sample approach can be easily translated to existing RNA-seq platforms. ATLAS can complement and guide traditional histopathologic assessment in challenging situations and tumors of unknown primary.
Post-ischemic ubiquitination at the postsynaptic density reversibly influences the activity of ischemia-relevant kinases
Authors: Dhawka Luvna , Palfini Victoria , Hambright Emma , Blanco Ismary , Poon Carrie , Kahl Anja , Resch Ulrike , Bhawal Ruchika , Benakis Corinne , Balachandran Vaishali , Holder Alana , Zhang Sheng , Iadecola Costantino , Hochrainer Karin
Published: March 2024

Ubiquitin modifications alter protein function and stability, thereby regulating cell homeostasis and viability, particularly under stress. Ischemic stroke induces protein ubiquitination at the ischemic periphery, wherein cells remain viable, however the identity of ubiquitinated proteins is unknown. Here, we employed a proteomics approach to identify these proteins in mice undergoing ischemic stroke. The data are available in a searchable web interface (https://hochrainerlab.shinyapps.io/StrokeUbiOmics/). We detected increased ubiquitination of 198 proteins, many of which localize to the postsynaptic density (PSD) of glutamatergic neurons. Among these were proteins essential for maintaining PSD architecture, such as PSD95, as well as NMDA and AMPA receptor subunits. The largest enzymatic group at the PSD with elevated post-ischemic ubiquitination were kinases, such as CaMKII, PKC, Cdk5, and Pyk2, whose aberrant activities are well-known to contribute to post-ischemic neuronal death. Concurrent phospho-proteomics revealed altered PSD-associated phosphorylation patterns, indicative of modified kinase activities following stroke. PSD-located CaMKII, PKC, and Cdk5 activities were decreased while Pyk2 activity was increased after stroke. Removal of ubiquitin restored kinase activities to pre-stroke levels, identifying ubiquitination as the responsible molecular mechanism for post-ischemic kinase regulation. These findings unveil a previously unrecognized role of ubiquitination in the regulation of essential kinases involved in ischemic injury.
Emergence of quantum confinement in topological kagome superconductor CsV3Sb5
Authors: Cai Yongqing , Wang Yuan , Hao Zhanyang , Liu Yixuan , Sui Xuelei , Liang Zuowei , Ma Xiao-Ming , Zhang Fayuan , Shen Zecheng , Zhang Chengcheng , Jiang Zhicheng , Yang Yichen , Liu Wanling , Jiang Qi , Liu Zhengtai , Ye Mao , Shen Dawei , Gao Han , Xiao Hanbo , Liu Zhongkai , Sun Zhe , Liu Yi , Cui Shengtao , Chen Jiabin , Wang Le , Liu Cai , Lin Junhao , Huang Bing , Wang Zhenyu , Chen Xianhui , Mei Jia-Wei , Wang Jianfeng , Chen Chaoyu
Published: March 2024

Quantum confinement is a restriction on the motion of electrons in a material to specific region, resulting in discrete energy levels rather than continuous energy bands. In certain materials, quantum confinement could dramatically reshape the electronic structure and properties of the surface with respect to the bulk. Here, in the recently discovered kagome superconductors CsV3Sb5, we unveil the dominant role of quantum confinement in determining their surface electronic structure. Combining angle-resolved photoemission spectroscopy (ARPES) measurement and density-functional theory simulation, we report the observations of two-dimensional quantum well states due to the confinement of bulk electron pocket and Dirac cone to the nearly isolated surface layer. The theoretical calculations on the slab model also suggest that the ARPES observed spectra are almost entirely contributed by the top two layers. Our results not only explain the disagreement of band structures between the recent experiments and calculations, but also suggest an equally important role played by quantum confinement, together with strong correlation and band topology, in shaping the electronic properties of this material.
How, when and where current mass flows in Martian gullies are driven by CO2 sublimation
Authors: Roelofs Lonneke , Conway Susan J. , de Haas Tjalling , Dundas Colin , Lewis Stephen R. , McElwaine Jim , Pasquon Kelly , Raack Jan , Sylvest Matthew , Patel Manish R.
Published: March 2024

Martian gullies resemble water-carved gullies on Earth, yet their present-day activity cannot be explained by water-driven processes. The sublimation of CO2 has been proposed as an alternative driver for sediment transport, but how this mechanism works remains unknown. Here we combine laboratory experiments of CO2-driven granular flows under Martian atmospheric pressure with 1D climate simulation modelling to unravel how, where, and when CO2 can drive present-day gully activity. Our work shows that sublimation of CO2 ice, under Martian atmospheric conditions can fluidize sediment and creates morphologies similar to those observed on Mars. Furthermore, the modelled climatic and topographic boundary conditions for this process, align with present-day gully activity. These results have implications for the influence of water versus CO2-driven processes in gully formation and for the interpretation of gully landforms on other planets, as their existence is no longer definitive proof for flowing liquids.