bluuebunny/crossref_metadata_2025 huggingface dataset:
Streamflow Prediction at the Intersection of Physics and Machine Learning: A Case Study of Two Mediterranean‐Climate Watersheds
Authors: Adera S. , Bellugi D. , Dhakal A. , Larsen L.
Published: July 2024

Accurate streamflow predictions are essential for water resources management. Recent studies have examined the use of hybrid models that integrate machine learning models with process‐based (PB) hydrologic models to improve streamflow predictions. Yet, there are many open questions regarding optimal hybrid model construction, especially in Mediterranean‐climate watersheds that experience pronounced wet and dry seasons. In this study, we performed model benchmarking to (a) compare hybrid model performance to PB and machine learning models and (b) examine the sensitivity of hybrid model performance to PB model parameter calibration, structural complexity, and variable selection. Hybrid models were generated by post‐processing process‐based models using Long Short‐Term Memory neural networks. Models were benchmarked within two northern California watersheds that are managed for both municipal water supplies and aquatic habitat. Though model performance varied substantially by watershed and error metric, calibrated hybrid models frequently outperformed both the machine learning model (for 72% of watershed‐model‐metric combinations) and the calibrated process‐based models (for 79% of combinations). Furthermore, hybrid models were relatively insensitive to PB model calibration and structural complexity, but sensitive to PB model variable selection. Our results demonstrate that hybrid models can improve streamflow prediction in Mediterranean‐climate watersheds. Additionally, hybrid model insensitivity to PB model parameter calibration and structural complexity suggests that uncalibrated or less complex PB models could be used in hybrid models without any loss of streamflow prediction accuracy, improving model construction efficiency. Moreover, hybrid model sensitivity to the selection of PB model variables suggests a strategy for diagnosing poorly performing PB model components.
Assessments of Arctic Cloud Vertical Structure From AIRS Using Radar‐Lidar Observations
Authors: Wang Xi , Liu Jian
Published: July 2024

The Atmospheric InfraRed Sounder (AIRS) aboard Aqua provides essential long‐term data on vertical cloud fraction, particularly valuable in the Arctic region. This study offers a comprehensive assessment of Arctic vertical cloud fraction derived from AIRS through a comparison with independent ground‐ and space‐based radar and lidar observations. In comparison to the measurements at the North Slope Alaska site, results reveal a significant underestimation of low‐level cloud cover by AIRS, especially for near‐surface clouds, while mid‐ and high‐level cloud fractions show better consistency. In comparison to the satellite‐based product from 3S‐GEOPROF‐COMB, the accuracy varies across different underlying surfaces (land vs. sea) and seasons. AIRS shows significant positive biases in mid‐level cloud fraction over sea surfaces with sea ice concentration below 15%, indicating potential limitations in the cloud retrieval algorithm in regions with large sea ice variations. The issue of low‐level clouds identification is primarily caused by the limited penetrating capability of infrared hyperspectral sensing and the accuracy of preceding surface and atmospheric state products, which diminish the accuracy of AIRS low‐level cloud fraction.
Electrical stimulation for brighter persistent luminescence
Authors: Ma Xilin , Wang Yuhua , Seto Takatoshi
Published: July 2024

An immature understanding of the mechanisms of persistent luminescence (PersL) has hindered the development of new persistent luminescent materials (PersLMs) with increased brightness. In this regard, in-situ direct current (DC) electric field measurements were conducted on a layered structure composed of the SrAl2O4:Eu2+,Dy3+ phosphor, and an electrode. In this study, the photoluminescence (PL) and afterglow properties were investigated with respect to voltage by analyzing the current signal and thermoluminescence (TL) spectroscopy. The intensity of PersL increased due to a novel phenomenon known as “external electric field stimulated enhancement of initial brightness of afterglow”. This dynamic process was illustrated via the use of a rate equation approach, where the electrons trapped by the ultra-shallow trap at 0.022 eV could be transferred through the conduction band during long afterglow. The afterglow intensity could reach 0.538 cd m−2 at a 6 V electric voltage. The design of an electric field stimulation technique enables the enhancement of the intensity of PersLMs and provides a new perspective for exploring the fundamental mechanics of certain established PersLMs.
Estrogen receptor beta signaling enhances extinction memory recall for heroin-conditioned cues in a sex- and region-specific manner
Authors: Carter Jordan S. , Costa Caitlyn C. , Lewandowski Stacia I. , Nelson Katharine H. , Goldsmith Sarah T. , Scofield Michael D. , Reichel Carmela M.
Published: July 2024

Return to use, or relapse, is a major challenge in the treatment of opioid use disorder (OUD). Relapse can be precipitated by several factors, including exposure to drug-conditioned cues. Identifying successful treatments to mitigate cue-induced relapse has been challenging, perhaps due to extinction memory recall (EMR) deficits. Previously, inhibition of estradiol (E2) signaling in the basolateral amygdala (BLA) impaired heroin-cue EMR. This effect was recapitulated by antagonism of BLA estrogen receptors (ER) in a sex-specific manner such that blocking ERα in males, but ERβ in females, impaired EMR. However, it is unclear whether increased E2 signaling, in the BLA or systemically, enhances heroin-cue EMR. We hypothesized that ERβ agonism would enhance heroin-cue EMR in a sex- and region-specific manner. To determine the capacity of E2 signaling to improve EMR, we pharmacologically manipulated ERβ across several translationally designed experiments. First, male and female rats acquired heroin or sucrose self-administration. Next, during a cued extinction session, we administered diarylpropionitrile (DPN, an ERβ agonist) and tested anxiety-like behavior on an open field. Subsequently, we assessed EMR in a cue-induced reinstatement test and, finally, measured ERβ expression in several brain regions. Across all experiments, females took more heroin and sucrose than males and had greater responses during heroin-cued extinction. Administration of DPN in the BLA enhanced EMR in females only, driven by ERβ’s impacts on memory consolidation. Interestingly, however, systemic DPN administration improved EMR for heroin cues in both sexes across several different tests, but did not impact sucrose-cue EMR. Immunohistochemical analysis of ERβ expression across several different brain regions showed that females only had greater expression of ERβ in the basal nucleus of the BLA. Here, in several preclinical experiments, we demonstrated that ERβ agonism enhances heroin-cue EMR and has potential utility in combatting cue-induced relapse.
Trauma, adversity, and biological aging: behavioral mechanisms relevant to treatment and theory
Authors: Bourassa Kyle J. , Sbarra David A.
Published: July 2024

Although stress and adversity are largely universal experiences, people exposed to greater hardship are at increased risk for negative health consequences. Recent studies identify accelerated biological aging as a mechanism that could explain how trauma and adversity gives rise to poor health, and advances in this area of study coincide with technological innovations in the measurement of biological aging, particularly epigenetic profiles consistent with accelerated aging derived from DNA methylation. In this review, we provide an overview of the current literature examining how adversity might accelerate biological aging, with a specific focus on social and health behaviors. The most extensive evidence in this area suggests that health-compromising behaviors, particularly smoking, may partially explain the association between adversity and accelerated aging. Although there is relatively less published support for the role of social behaviors, emerging evidence points to the importance of social connection as a mechanism for future study. Our review highlights the need to determine the extent to which the associations from adversity to accelerated aging are consistent with causal processes. As we consider these questions, the review emphasizes methodological approaches from the causal inference literature that can help deepen our understanding of how stress and trauma might result in poor health. The use of these methodologies will help provide evidence as to which behavioral interventions might slow aging and improve health, particularly among populations that more often experience adversity and trauma.
The infrapatellar fat pad in inflammaging, knee joint health, and osteoarthritis
Authors: Wang Magnolia G. , Seale Patrick , Furman David
Published: July 2024

Osteoarthritis (OA) is the most common form of arthritis and accounts for nearly $140 billion in annual healthcare expenditures only in the United States. Obesity, aging, and joint injury are major risk factors for OA development and progression, but the mechanisms contributing to pathology remain unclear. Emerging evidence suggests that cellular dysregulation and inflammation in joint tissues, including intra-articular adipose tissue depots, may contribute to disease severity. In particular, the infrapatellar fat pad (IFP), located in the knee joint, which provides a protective cushion for joint loading, also secretes multiple endocrine factors and inflammatory cytokines (inflammaging) that can regulate joint physiology and disease. Correlates of cartilage degeneration and OA-associated disease severity include inflammation and fibrosis of IFP in model organisms and human studies. In this article, we discuss recent progress in understanding the roles and regulation of intra-articular fat tissue in regulating joint biology and OA.
Detailed study of a rare hyperluminous rotating disk in an Einstein ring 10 billion years ago
Authors: Liu Daizhong , Förster Schreiber Natascha M. , Harrington Kevin C. , Lee Lilian L. , Kamieneski Patrick S. , Davies Richard I. , Lutz Dieter , Renzini Alvio , Wuyts Stijn , Tacconi Linda J. , Genzel Reinhard , Burkert Andreas , Herrera-Camus Rodrigo , Alcalde Pampliega Belén , Vishwas Amit , Kaasinen Melanie , Wang Q. Daniel , Jiménez-Andrade Eric F. , Lowenthal James , Foo Nicholas , Frye Brenda L. , Shangguan Jinyi , Cao Yixian , Agapito Guido , Berbel Alex Agudo , Barfety Capucine , Baruffolo Andrea , Berman Derek , Black Martin , Bonaglia Marco , Briguglio Runa , Carbonaro Luca , Chapman Lee , Chen Jianhang , Cikota Aleksandar , Concas Alice , Cooper Olivia , Cresci Giovanni , Dallilar Yigit , Deysenroth Matthias , Di Antonio Ivan , Di Cianno Amico , Di Rico Gianluca , Doelman David , Dolci Mauro , Eisenhauer Frank , Espejo Juan , Esposito Simone , Fantinel Daniela , Ferruzzi Debora , Feuchtgruber Helmut , Gao Xiaofeng , Garcia Diaz Carlos , Gillessen Stefan , Grani Paolo , Hartl Michael , Henry David , Huber Heinrich , Jolly Jean-Baptiste , Keller Christoph U. , Kenworthy Matthew , Kravchenko Kateryna , Lee Minju M. , Lightfoot John , Lunney David , Macintosh Mike , Mannucci Filippo , Ott Thomas , Pascale Massimo , Pastras Stavros , Pearson David , Puglisi Alfio , Pulsoni Claudia , Rabien Sebastian , Rau Christian , Riccardi Armando , Salasnich Bernardo , Shimizu Taro , Snik Frans , Sturm Eckhard , Taylor William , Valentini Angelo , Waring Christopher , Wiezorrek Erich , Xompero Marco , Yun Min S.
Published: July 2024

Hyperluminous infrared galaxies (HyLIRGs) are the rarest and most extreme starbursts and found only in the distant Universe (z ≳ 1). They have intrinsic infrared (IR) luminositiesLIR ≥ 1013 L⊙and are commonly found to be major mergers. Recently, the Planck All-Sky Survey to Analyze Gravitationally-lensed Extreme Starbursts project (PASSAGES) searched ~104deg2of the sky and found ~20 HyLIRGs. We describe a detailed study of PJ0116-24, the brightest (μLIR ≈ 2.6 × 1014 L⊙, magnified withμ ≈ 17) Einstein-ring HyLIRG in the southern sky, atz = 2.125, with observations from the near-IR integral-field spectrograph VLT/ERIS and the submillimetre interferometer ALMA. We detected Hα, Hβ, [Nii] and [Sii] lines and obtained an extreme Balmer decrement (Hα/Hβ ≈ 8.73 ± 1.14). We modelled the molecular-gas and ionized-gas kinematics with CO(3–2) and Hα data at ~100–300 pc and (sub)kiloparsec delensed scales, respectively, finding consistent regular rotation. We found PJ0116-24 to be highly rotationally supported (vrot/σ0, mol. gas ≈ 9.4) with a richer gaseous substructure than other known HyLIRGs. Our results imply that PJ0116-24 is an intrinsically massive (Mbaryon ≈ 1011.3 M⊙) and rare starbursty disk (star-formation rate, SFR = 1,490 M⊙ yr−1) probably undergoing secular evolution. This indicates that the maximal SFR (≳1,000 M⊙ yr−1) predicted by simulations could occur during a galaxy’s secular evolution, away from major mergers.
Gut microbial factors predict disease severity in a mouse model of multiple sclerosis
Authors: Steimle Alex , Neumann Mareike , Grant Erica T. , Willieme Stéphanie , De Sciscio Alessandro , Parrish Amy , Ollert Markus , Miyauchi Eiji , Soga Tomoyoshi , Fukuda Shinji , Ohno Hiroshi , Desai Mahesh S.
Published: July 2024

Gut bacteria are linked to neurodegenerative diseases but the risk factors beyond microbiota composition are limited. Here we used a pre-clinical model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE), to identify microbial risk factors. Mice with different genotypes and complex microbiotas or six combinations of a synthetic human microbiota were analysed, resulting in varying probabilities of severe neuroinflammation. However, the presence or relative abundances of suspected microbial risk factors failed to predict disease severity. Akkermansia muciniphila, often associated with MS, exhibited variable associations with EAE severity depending on the background microbiota. Significant inter-individual disease course variations were observed among mice harbouring the same microbiota. Evaluation of microbial functional characteristics and host immune responses demonstrated that the immunoglobulin A coating index of certain bacteria before disease onset is a robust individualized predictor of disease development. Our study highlights the need to consider microbial community networks and host-specific bidirectional interactions when aiming to predict severity of neuroinflammation.
Revealing the three-dimensional structure of microbunched plasma-wakefield-accelerated electron beams
Authors: LaBerge Maxwell , Bowers Brant , Chang Yen-Yu , Couperus Cabadağ Jurjen , Debus Alexander , Hannasch Andrea , Pausch Richard , Schöbel Susanne , Tiebel Jessica , Ufer Patrick , Willmann Anna , Zarini Omid , Zgadzaj Rafal , Lumpkin Alex H. , Schramm Ulrich , Irman Arie , Downer M. C.
Published: July 2024

Plasma wakefield accelerators use tabletop equipment to produce relativistic femtosecond electron bunches. Optical and X-ray diagnostics have established that their charge concentrates within a micrometre-sized volume, but its sub-micrometre internal distribution, which critically influences gain in free-electron lasers or particle yield in colliders, has proven elusive to characterize. Here, by simultaneously imaging different wavelengths of coherent optical transition radiation that a laser-wakefield-accelerated electron bunch generates when exiting a metal foil, we reveal the structure of the coherently radiating component of bunch charge. The key features of the images are shown to uniquely correlate with how plasma electrons injected into the wake: by a plasma-density discontinuity, by ionizing high-Z gas-target dopants or by uncontrolled laser–plasma dynamics. With additional input from the electron spectra, spatially averaged coherent optical transition radiation spectra and particle-in-cell simulations, we reconstruct coherent three-dimensional charge structures. The results demonstrate an essential metrology for next-generation compact X-ray free-electron lasers driven by plasma-based accelerators.
Familial clustering of dysbiotic oral and fecal microbiomes in juvenile dermatomyositis
Authors: Koester Sean T. , Chow Albert , Pepper-Tunick Evan , Lee Peggy , Eckert Mary , Brenchley Laurie , Gardner Pamela , Song Hyun Jung , Li Naisi , Schiffenbauer Adam , Volochayev Rita , Bayat Nastaran , McLean Jeffrey S. , Rider Lisa G. , Shenoi Susan , Stevens Anne M. , Dey Neelendu
Published: July 2024

Juvenile dermatomyositis (JDM) is a rare immune-mediated disease of childhood with putative links to microbial exposures. In this multi-center, prospective, observational cohort study, we evaluated whether JDM is associated with discrete oral and gut microbiome signatures. We generated 16S rRNA sequencing data from fecal, saliva, supragingival, and subgingival plaque samples from JDM probands (n = 28). To control for genetic and environmental determinants of microbiome community structure, we also profiled microbiomes of unaffected family members (n = 27 siblings, n = 26 mothers, and n = 17 fathers). Sample type (oral-vs-fecal) and nuclear family unit were the predominant variables explaining variance in microbiome diversity, more so than having a diagnosis of JDM. The oral and gut microbiomes of JDM probands were more similar to their own unaffected siblings than they were to the microbiomes of other JDM probands. In a sibling-paired within-family analysis, several potentially immunomodulatory bacterial taxa were differentially abundant in the microbiomes of JDM probands compared to their unaffected siblings, including Faecalibacterium (gut) and Streptococcus (oral cavity). While microbiome features of JDM are often shared by unaffected family members, the loss or gain of specific fecal and oral bacteria may play a role in disease pathogenesis or be secondary to immune dysfunction in susceptible individuals.
Alcohol consumption during pregnancy differentially affects the fecal microbiota of dams and offspring
Authors: Bodnar Tamara S. , Ainsworth-Cruickshank Garrett , Billy Vincent , Wegener Parfrey Laura , Weinberg Joanne , Raineki Charlis
Published: July 2024

Microbiota imbalances are linked to inflammation and disease, as well as neurodevelopmental conditions where they may contribute to behavioral, physiological, and central nervous system dysfunction. By contrast, the role of the microbiota in Fetal Alcohol Spectrum Disorder (FASD), the group of neurodevelopmental conditions that can occur following prenatal alcohol exposure (PAE), has not received similar attention. Here we utilized a rodent model of alcohol consumption during pregnancy to characterize the impact of alcohol on the microbiota of dam-offspring dyads. Overall, bacterial diversity decreased in alcohol-consuming dams and community composition differed from that of controls in alcohol-consuming dams and their offspring. Bacterial taxa and predicted biochemical pathway composition were also altered with alcohol consumption/exposure; however, there was minimal overlap between the changes in dams and offspring. These findings illuminate the potential importance of the microbiota in the pathophysiology of FASD and support investigation into novel microbiota-based interventions.
G0-PCC-FISH derived multi-parametric biodosimetry methodology for accidental high dose and partial body exposures
Authors: Yadav Usha , Bhat Nagesh N. , Mungse Utkarsha S. , Shirsath Kapil B. , Joshi Manish , Sapra Balvinder K.
Published: July 2024

High dose radiation exposures are rare. However, medical management of such incidents is crucial due to mortality and tissue injury risks. Rapid radiation biodosimetry of high dose accidental exposures is highly challenging, considering that they usually involve non uniform fields leading to partial body exposures. The gold standard, dicentric assay and other conventional methods have limited application in such scenarios. As an alternative, we propose Premature Chromosome Condensation combined with Fluorescent In-situ Hybridization (G0-PCC-FISH) as a promising tool for partial body exposure biodosimetry. In the present study, partial body exposures were simulated ex-vivo by mixing of uniformly exposed blood with unexposed blood in varying proportions. After G0-PCC-FISH, Dolphin’s approach with background correction was used to provide partial body exposure dose estimates and these were compared with those obtained from conventional dicentric assay and G0-PCC-Fragment assay (conventional G0-PCC). Dispersion analysis of aberrations from partial body exposures was carried out and compared with that of whole-body exposures. The latter was inferred from a multi-donor, wide dose range calibration curve, a-priori established for whole-body exposures. With the dispersion analysis, novel multi-parametric methodology for discerning the partial body exposure from whole body exposure and accurate dose estimation has been formulated and elucidated with the help of an example. Dose and proportion dependent reduction in sensitivity and dose estimation accuracy was observed for Dicentric assay, but not in the two PCC methods. G0-PCC-FISH was found to be most accurate for the dose estimation. G0-PCC-FISH has potential to overcome the shortcomings of current available methods and can provide rapid, accurate dose estimation of partial body and high dose accidental exposures. Biological dose estimation can be useful to predict progression of disease manifestation and can help in pre-planning of appropriate & timely medical intervention.
Assessing accuracy and consistency in intracranial aneurysm sizing: human expertise vs. artificial intelligence
Authors: Planinc Andrej , Špegel Nina , Podobnik Zala , Šinigoj Uroš , Skubic Petra , Choi June Ho , Park Wonhyoung , Robič Tina , Tabor Nika , Jarabek Leon , Špiclin Žiga , Bizjak Žiga
Published: July 2024

Intracranial aneurysms (IAs) are a common vascular pathology and are associated with a risk of rupture, which is often fatal. Aneurysm growth of more than 1 mm is considered a surrogate of rupture risk, therefore, this study presents a comprehensive analysis of intracranial aneurysm measurements utilizing a dataset comprising 358 IA from 248 computed tomography angiography (CTA) scans measured by four junior raters and one senior rater. The study explores the variability in sizing assessments by employing both human raters and an Artificial Intelligence (AI) system. Our findings reveal substantial inter- and intra-rater variability among junior raters, contrasting with the lower intra-rater variability observed in the senior rater. Standard deviations of all raters were above the threshold for IA growth (1 mm). Additionally, the study identifies a systemic bias, indicating a tendency for human experts to measure aneurysms smaller than the AI system. Our findings emphasize the challenges in human assessment while also showcasing the capacity of AI technology to improve the precision and reliability of intracranial aneurysm assessments, especially beneficial for junior raters. The potential of AI was particularly evident in the task of monitoring IA at various intervals, where the AI-based approach surpassed junior raters and achieved performance comparable to senior raters.
Comprehensive analysis and implications of Veronica persica germination and growth traits in their invasion ecology
Authors: Al-Qthanin Rahmah , Radwan Asmaa M. , Donia AbdElRaheim M. , Balah Mohamed A.
Published: July 2024

Invasive alien species implications in ecological threats are attributed to their unique characteristics that are linked to their invasion. Veronica persica (Plantaginaceae family) is an alien weed species in Egypt. Regardless of its widespread globally in various regions, the growth traits and behavior of V. persica remain poorly understood. The comprehensive analysis, reveals the optimal germination (Gmax) was detected at 10/20 °C, 15/20 °C, and 20/25 °C at the moderate temperature regimes. The rapid germination rate (G rate) peaked at 10/20 °C regime, with a rate of 0.376 per day. Furthermore, under stress conditions, V. persica has 50% germination inhibition (G50) and 50% of growth inhibition occurred at − 0.91 MPa and 0.75 MPa of osmotic pressure and 3225.81 ppm and 2677.1 ppm of salt stress (NaCl) respectively. The germination ranged from 6 to 9 pH, with the highest germination percentage occurring at a pH of 7 & 8, reaching 88.75% compared to the control group. There is a strong interaction effect between habitats and plant stages, the plant stages and habitats have significant effects (p ≤ 0.00) on V. persica growth. There was high and moderate plasticity in the response of morphological and growth features between stages. During the seedling-juvenile interval and the juvenile-flowering stages, respectively, there was a noticeable increase in both Relative Growth Rate and Net Assimilation Rate. Demographic surveys identified approximately 24 species across 11 families associated with V. persica in invaded areas. The Sorenson indices of qualitative index exhibited high similarity values in the invaded sites by (82.35%) compared to (72.72%) in non-invaded sites. However, interactions with native communities were reflected in lower richness, diversity, and evenness, displaying slightly higher Simpson index 1 (λ) values compared to invaded and non-invaded sites (0.043 and 0.0290) vs. (0.0207 and 0.268), in rangelands and F. carica orchards respectively. These results emphasize the substantially higher adaptability of V. persica to variable environmental conditions and abilities to invade a new community. This knowledge about invasive V. persica weeds germination and growth is itemized as the consistent predictive base for future invasion and informs strategic management priorities.
Double closed loop PI control with full compensation arc elimination based on zero sequence voltage of neutral point
Authors: Liu Hongwen , Zeng Xiangjun , yang Qing , Chai Chenchao
Published: July 2024

Aiming at the problem of zero sequence voltage generated by unbalance parameters of line to ground, which affects arc suppression effect of grounding fault of controllable voltage source. By analyzing the influence of ground unbalance parameters on the arc suppression effect of controllable voltage source under different grounding modes, the mechanism of full compensation arc suppression based on zero sequence voltage of neutral point is revealed, and on this basis, a fully compensated arc suppression model of controllable voltage source controlled by double closed loop PI is established, and the deviation control is carried out by using the neutral voltage of distribution network and the voltage of fault phase supply. The residual voltage ring adopts the ground fault phase residual voltage for closed loop control. The simulation results show that the dual-closed-loop PI control algorithm can continuously stabilize the output waveform of the controllable voltage source. When the transition resistance is 0.1 ~ 10 kΩ, the residual voltage stabilization time of the independent controllable voltage source grounding method is 43 ms ~ 2.4 s, and the parallel arc suppression coil grounding method is 43 ms ~ 4.7 s. The proposed dual closed-loop PI control method for neutral point voltage deviation and fault residual voltage can stabilize the residual voltage of the grounded fault phase to below 10 V, forcing reliable arc extinction at the grounded fault point, exhibiting good stability. Low-voltage simulation tests have also proved the feasibility of the algorithm.
In vivo turnover and biodistribution of soluble AXL: implications for biomarker development
Authors: Tenstad Olav , Christakou Eleni , Hodneland Nilsson Linn , Gausdal Gro , Micklem David , Kursula Petri , Lorens James B. , Reed Rolf K.
Published: July 2024

Soluble biomarkers are paramount to personalized medicine. However, the in vivo turnover and biodistribution of soluble proteins is seldom characterized. The cleaved extracellular domain of the AXL receptor (sAXL) is a prognostic biomarker in several diseases and a predictive marker of AXL targeting agents. Plasma sAXL reflects a balance between production in tissues with lymphatic transport into the circulation and removal from blood by degradation or excretion. It is unclear how this transport cycle affects plasma sAXL levels that are the metric for biomarker development. Radiolabeled mouse sAxl was monitored after intravenous injection to measure degradation and urinary excretion of sAxl, and after intradermal injection to mimic tissue or tumor production. sAxl was rapidly taken-up and degraded by the liver and kidney cortex. Surprisingly, intact sAxl was detectable in urine, indicating passage through the glomerular filter and a unique sampling opportunity. The structure of sAxl showed an elongated, flexible molecule with a length of 18 nm and a thickness of only 3 nm, allowing passage through the glomerulus and excretion into the urine. Intradermally injected sAxl passed through local and distant lymph nodes, followed by uptake in liver and kidney cortex. Low levels of sAxl were seen in the plasma, consistent with an extended transit time from local tissue to circulation. The rapid plasma clearance of sAxl suggests that steady-state levels in blood will sensitively and dynamically reflect the rate of production of sAxl in the tissues but will be influenced by perturbations of liver and kidney function.
Parallel ensemble of a randomization-based online sequential neural network for classification problems using a frequency criterion
Authors: Gelvez-Almeida Elkin , Barrientos Ricardo J. , Vilches-Ponce Karina , Mora Marco
Published: July 2024

Randomization-based neural networks have gained wide acceptance in the scientific community owing to the simplicity of their algorithm and generalization capabilities. Random vector functional link (RVFL) networks and their variants are a class of randomization-based neural networks. RVFL networks have shown promising results in classification, regression, and clustering problems. For real-world applications, learning algorithms that can train with new samples over previous results are necessary because of to the constant generation of problems related to large-scale datasets. Various online sequential algorithms, commonly involving an initial learning phase followed by a sequential learning phase, have been proposed to address this issue. This paper presents a training algorithm based on multiple online sequential random vector functional link (OS-RVFL) networks for large-scale databases using a shared memory architecture. The training dataset is distributed among p OS-RVFL networks, which are trained in parallel using p threads. Subsequently, the test dataset samples are classified using each trained OS-RVFL network. Finally, a frequency criterion is applied to the results obtained from each OS-RVFL network to determine the final classification. Additionally, an equation was derived to reasonably predict the total training time of the proposed algorithm based on the learning time in the initial phase and the time scaling factor compared to the sequential learning phase. The results demonstrate a drastic reduction in training time because of data distribution and an improvement in accuracy because of the adoption of the frequency criterion.
ActivinA modulates B-acute lymphoblastic leukaemia cell communication and survival by inducing extracellular vesicles production
Authors: Licari Eugenia , Cricrì Giulia , Mauri Mario , Raimondo Francesca , Dioni Laura , Favero Chiara , Giussani Alice , Starace Rita , Nucera Silvia , Biondi Andrea , Piazza Rocco , Bollati Valentina , Dander Erica , D’Amico Giovanna
Published: July 2024

Extracellular vesicles (EVs) are a new mechanism of cellular communication, by delivering their cargo into target cells to modulate molecular pathways. EV-mediated crosstalk contributes to tumor survival and resistance to cellular stress. However, the role of EVs in B-cell Acute Lymphoblastic Leukaemia (B-ALL) awaits to be thoroughly investigated. We recently published that ActivinA increases intracellular calcium levels and promotes actin polymerization in B-ALL cells. These biological processes guide cytoskeleton reorganization, which is a crucial event for EV secretion and internalization. Hence, we investigated the role of EVs in the context of B-ALL and the impact of ActivinA on this phenomenon. We demonstrated that leukemic cells release a higher number of EVs in response to ActivinA treatment, and they can actively uptake EVs released by other B-ALL cells. Under culture-induced stress conditions, EVs coculture promoted cell survival in B-ALL cells in a dose-dependent manner. Direct stimulation of B-ALL cells with ActivinA or with EVs isolated from ActivinA-stimulated cells was even more effective in preventing cell death. This effect can be possibly ascribed to the increase of vesiculation and modifications of EV-associated microRNAs induced by ActivinA. These data demonstrate that ActivinA boosts EV-mediated B-ALL crosstalk, improving leukemia survival in stress conditions.
Non-insulin-based insulin resistance indices predict early neurological deterioration in elderly and middle-aged acute ischemic stroke patients in Northeast China
Authors: Wang Jia , Tang Hao , Tian Jianan , Xie Yibo , Wu Yun
Published: July 2024

Insulin resistance (IR) has a strong association with acute ischemic stroke (AIS) occurrence and poor prognosis of afflicted patients. However, the relation between early neurological deterioration (END) risk and IR in elderly and middle-aged patients remains to be thoroughly studied. Here, we investigated the relationship between four indicators of IR and the risk of END in middle-aged patients patients with AIS. The study retrospectively analyzed 1696 elderly and middle-aged patients having AIS between January 2019 and June 2023. Within 7 days of admission, the patients were then stratified relying upon alternations in the National Institutes of Health Stroke Scale. Subsequently, we employed logistic regression analyses for assessing each index correlation with END on the basis of the tertiles of TyG index (TyGI), triglyceride to high-density lipoprotein ratio (TG/HDL), TyG-BMI, alongside IR metabolic score (METS-IR). These four indicators were significantly heightened in the END group (n = 680) in comparison to the non-END group (n = 1016). When grouping using tertiles, the four aforementioned indicators emerged as independent risk factors for END occurrence, whether or not adjusted for confounding factors. The results revealed a progressive elevation in END occurrence risk with the rise in the tertile of each indicator. Finally, we utilized receiver operating characteristic (ROC) curves for assessing the indicators' predictive power. TyG-BMI, TyGI, TG/HDL, and METS-IRs’ area under the curve (AUC) were, respectively, 0.736 (95% CI: 0.712–0.761; P < 0.001), 0. 694 (95% CI: 0.668–0.721; P < 0.001), 0.684 (95% CI: 0.658–0.711; P < 0.001), and 0.722 (95% CI: 0.697–0.747; P < 0.001). IR is associated with END risk in middle-aged AIS patients. TyG-BMI, TyGI, TG/HDL, and METS-IR are independent risk factors of END in elderly and middle-aged AIS patients. Simultaneously, these four IR indicators have significant predictive power for END.
Depressive symptoms among individuals identifying as asexual: a cross-sectional study
Authors: Lech Sonia , Köppe Monia , Berger Maximilian , Alonso-Perez Enrique , Gellert Paul , Herrmann Wolfram , Buspavanich Pichit
Published: July 2024

Although asexuality became a growing research subject over the last decade, data on the mental health of individuals identifying as asexual is still rare. The key objective of the present study was to examine depressive symptoms among individuals identifying as asexual. Data of LGBTQIA+ (Lesbian, Gay, Bi-sexual, Trans*, Queer, Inter*, Asexual and/or + indicating others within the community) and cisgender heterosexual individuals was collected through an online survey during the COVID-19 lockdowns in Germany. The survey included questions about sexual and gender identity, depressive symptoms, and asexual identity. An analysis of N = 6601 participants was conducted. A total of n = 445 individuals identified as asexual. Regression results indicated identifying as asexual being significantly associated with higher depressive symptoms. Results suggest that individuals identifying as asexual represent a vulnerable group within the group of sexual minorities, one that fundamentally requires special psychosocial support, especially in times of pandemics.
Dynamics of single-nuclei transcriptomic profiling of adipose tissue from diverse anatomical locations during mouse aging process
Authors: Wu Yujie , Sun Ying , Chen Long , Tong Xingyan , Liu Can , Lu Lu , Zhang Rui , Wang Siyuan , Chen Ziyu , Zhang Jiaman , Han Ziyin , Zeng Bo , Li Mingzhou , Jin Long
Published: July 2024

Adipose tissue plays critical roles in an individual’s aging process. In this research, we use single-nucleus RNA sequencing to create highly detailed transcriptional maps of subcutaneous adipose tissue and visceral adipose tissue in young and aged mice. We comprehensively identify the various cell types within the white adipose tissue of mice, our study has elucidated seven distinct cell types within this tissue. Further analyses focus on adipocytes, fibro-adipogenic progenitors, and immune cells, revealing age-related declines in the synthetic metabolic activity of adipocytes, diminished immune regulation, and reduced maturation or proliferation of fibroblasts in undifferentiated adipocytes. We confirm the presence of distinct subpopulations of adipocytes, highlighting decreases in adipogenesis subgroups due to aging. Additionally, we uncover a reduction in immune cell subpopulations, driven by age-associated immune system dysregulation. Furthermore, pseudo-time analyses indicate that Adipocyte1 represents the 'nascent' phase of adipocyte development, while Adipocyte2 represents the 'mature' phase. We use cell–cell interaction to explore the age-dependent complexities of the interactions between FAPs and adipocytes, and observed increased expression of the inflammation-related Retn-Tlr4 interaction in older mice, while the anti-inflammatory Angpt1-Tek interaction was only detected in young mice. These transcriptional profiles serve as a valuable resource for understanding the functional genomics underlying metabolic disorders associated with aging in human adipose tissue.
Experimental and CFD analysis of fluid flow through nanofiber filter media
Authors: Azimian Mehdi , Naderi Matin , Soltani Parham , Cheng Liping , Naderi Keivan , Linden Sven , Wiegmann Andreas
Published: July 2024

This work presents a novel approach to investigating the slip effect in nanofiber filter media. Electrospun nanofiber media with high efficiency and low pressure drop were produced at different concentrations and durations. The surface and cross-sectional morphology of nanofiber media were studied using FE-SEM. Fiber orientation and diameter distributions were also examined. The 3D virtual nanofiber media was modeled using this information along with the experimentally measured porosity and thickness of the media. The effect of the slip phenomenon in nanofiber media was studied numerically, and the results were compared to experimental data. Excellent agreements were found between the measured and simulation results. Additionally, filtration simulations considering aerosols injected with airflow through the nanofibrous filter media were conducted by considering the slip effect, and the effect of filter structure on filtration performance (removal efficiency and pressure drop) was investigated.
Impact of corrupt admission on the mental health of Chinese adolescents
Authors: Yuan Hongbin , Li Danyang , Yang Feiran , Zhang Zhijian
Published: July 2024

Through preferential treatment by education officials or through bribery, some adolescents can obtain admission to a junior high school. However, it is unclear whether it affects the mental health of adolescents. This study used Propensity Score Matching to examine the effects of corruption on adolescent mental health. A total of 17,254 junior high school students sample (11–18 years old; 48.7% girls and 53.1% boys) were used from the China Education Panel Survey. 14.1% of adolescents attended a junior high school by corrupt means, corruption had a significantly negative effect on the mental health of these adolescents (ATT = −0.388, p < 0.01), the reasons grounded in the fact that they received more criticisms from teachers and wanted to leave their current school. In general, corruption in the admissions process can have detrimental effects on the mental health of adolescents. This study extends the previous articles on how to improve adolescent mental health and complements the application of cognitive dissonance theory. Findings from this study revealed that anti-corruption in the education sector is necessary, and the institutional design to ensure fair enrolment in basic education will contribute to the mental health of adolescents.
The SIRT2-AMPK axis regulates autophagy induced by acute liver failure
Authors: Zhang Qingqi , Guo Jin , Shi Chunxia , Zhang Danmei , Wang Yukun , Wang Luwen , Gong Zuojiong
Published: July 2024

This study explores the role of SIRT2 in regulating autophagy and its interaction with AMPK in the context of acute liver failure (ALF). This study investigated the effects of SIRT2 and AMPK on autophagy in ALF mice and TAA-induced AML12 cells. The results revealed that the liver tissue in ALF model group had a lot of inflammatory cell infiltration and hepatocytes necrosis, which were reduced by SIRT2 inhibitor AGK2. In comparison to normal group, the level of SIRT2, P62, MDA, TOS in TAA group were significantly increased, which were decreased in AGK2 treatment. Compared with normal group, the expression of P-PRKAA1, Becilin1 and LC3B-II was decreased in TAA group. However, AGK2 enhanced the expression of P-PRKAA1, Becilin1 and LC3B-II in model group. Overexpression of SIRT2 in AML12 cell resulted in decreased P-PRKAA1, Becilin1 and LC3B-II level, enhanced the level of SIRT2, P62, MDA, TOS. Overexpression of PRKAA1 in AML12 cell resulted in decreased SIRT2, TOS and MDA level and triggered more autophagy. In conclusion, the data suggested the link between AMPK and SIRT2, and reveals the important role of AMPK and SIRT2 in autophagy on acute liver failure.
Cytotoxic effects and comparative analysis of Ni ion uptake by osteoarthritic and physiological osteoblasts
Authors: Navratilova Polina , Vejvodova Marketa , Vaculovic Tomas , Slaninova Iva , Emmer Jan , Tomas Tomas , Ryba Ludek , Burda Jan , Pavkova Goldbergova Monika
Published: July 2024

Nickel(Ni)-containing materials have been widely used in a wide range of medical applications, including orthopaedics. Despite their excellent properties, there is still a problem with the release of nickel ions into the patient’s body, which can cause changes in the behaviour of surrounding cells and tissues. This study aims to evaluate the effects of Ni on bone cells with an emphasis on the determination of Ni localization in cellular compartments in time. For these purposes, one of the most suitable models for studying the effects induced by metal implants was used—the patient’s osteoarthritic cells. Thanks to this it was possible to simulate the pathophysiological conditions in the patient’s body, as well as to evaluate the response of the cells which come into direct contact with the material after the implantation of the joint replacement. The largest differences in cell viability, proliferation and cell cycle changes occurred between Ni 0.5 mM and 1 mM concentrations. Time-dependent localization of Ni in cells showed that there is a continuous transport of Ni ions between the nucleus and the cytoplasm, as well as between the cell and the environment. Moreover, osteoarthritic osteoblasts showed faster changes in concentration and ability to accumulate more Ni, especially in the nucleus, than physiological osteoblasts. The differences in Ni accumulation process explains the higher sensitivity of patient osteoblasts to Ni and may be crucial in further studies of implant-derived cytotoxic effects.
Prenatal genetic diagnosis of fetuses with dextrocardia using whole exome sequencing in a tertiary center
Authors: Xue Huili , Yu Aili , Chen Lingji , Guo Qun , Zhang Lin , lin Na , Chen Xuemei , Xu Liangpu , Huang Hailong
Published: July 2024

To evaluate the genetic etiology of fetal dextrocardia, associated ultrasound anomalies, and perinatal outcomes, we investigated the utility of whole exome sequencing (WES) for prenatal diagnosis of dextrocardia. Fetuses with dextrocardia were prospectively collected between January 2016 and December 2022. Trio-WES was performed on fetuses with dextrocardia, following normal karyotyping and/or chromosomal microarray analysis (CMA) results. A total of 29 fetuses with dextrocardia were collected, including 27 (93.1%) diagnosed with situs inversus totalis and 2 (6.9%) with situs inversus partialis. Cardiac malformations were present in nine cases, extra-cardiac anomalies were found in seven cases, and both cardiac and extra-cardiac malformations were identified in one case. The fetal karyotypes and CMA results of 29 cases were normal. Of the 29 cases with dextrocardia, 15 underwent WES, and the other 14 cases refused. Of the 15 cases that underwent WES, clinically relevant variants were identified in 5/15 (33.3%) cases, including the diagnostic variants DNAH5, DNAH11, LRRC56, PEX10, and ZIC3, which were verified by Sanger sequencing. Of the 10 cases with non-diagnostic results via WES, eight (80%) chose to continue the pregnancies. Of the 29 fetuses with dextrocardia, 10 were terminated during pregnancy, and 19 were live born. Fetal dextrocardia is often accompanied by cardiac and extra-cardiac anomalies, and fetal dextrocardia accompanied by situs inversus is associated with a high risk of primary ciliary dyskinesia. Trio-WES is recommended following normal karyotyping and CMA results because it can improve the diagnostic utility of genetic variants of fetal dextrocardia, accurately predict fetal prognosis, and guide perinatal management and the reproductive decisions of affected families.
Effects of experimental canopy openness on wood-inhabiting fungal fruiting diversity across succession
Authors: Schreiber Jasper , Baldrian Petr , Brabcová Vendula , Brandl Roland , Kellner Harald , Müller Jörg , Roy Friederike , Bässler Claus , Krah Franz-Sebastian
Published: July 2024

While the succession of terrestrial plant communities is well studied, less is known about succession on dead wood, especially how it is affected by environmental factors. While temperate forests face increasing canopy mortality, which causes considerable changes in microclimates, it remains unclear how canopy openness affects fungal succession. Here, we used a large real-world experiment to study the effect of closed and opened canopy on treatment-based alpha and beta fungal fruiting diversity. We found increasing diversity in early and decreasing diversity at later stages of succession under both canopies, with a stronger decrease under open canopies. However, the slopes of the diversity versus time relationships did not differ significantly between canopy treatments. The community dissimilarity remained mainly stable between canopies at ca. 25% of species exclusively associated with either canopy treatment. Species exclusive in either canopy treatment showed very low number of occupied objects compared to species occurring in both treatments. Our study showed that canopy loss subtly affected fungal fruiting succession on dead wood, suggesting that most species in the local species pool are specialized or can tolerate variable conditions. Our study indicates that the fruiting of the fungal community on dead wood is resilient against the predicted increase in canopy loss in temperate forests.