bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping cell-to-tissue graphs across human placenta histology whole slide images using deep learning with HAPPY
Authors: Vanea Claudia , Džigurski Jelisaveta , Rukins Valentina , Dodi Omri , Siigur Siim , Salumäe Liis , Meir Karen , Parks W. Tony , Hochner-Celnikier Drorith , Fraser Abigail , Hochner Hagit , Laisk Triin , Ernst Linda M. , Lindgren Cecilia M. , Nellåker Christoffer 
Published: March 2024

AbstractAccurate placenta pathology assessment is essential for managing maternal and newborn health, but the placenta’s heterogeneity and temporal variability pose challenges for histology analysis. To address this issue, we developed the ‘Histology Analysis Pipeline.PY’ (HAPPY), a deep learning hierarchical method for quantifying the variability of cells and micro-anatomical tissue structures across placenta histology whole slide images. HAPPY differs from patch-based features or segmentation approaches by following an interpretable biological hierarchy, representing cells and cellular communities within tissues at a single-cell resolution across whole slide images. We present a set of quantitative metrics from healthy term placentas as a baseline for future assessments of placenta health and we show how these metrics deviate in placentas with clinically significant placental infarction. HAPPY’s cell and tissue predictions closely replicate those from independent clinical experts and placental biology literature.
SpiDe-Sr: blind super-resolution network for precise cell segmentation and clustering in spatial proteomics imaging
Authors: Chen Rui , Xu Jiasu , Wang Boqian , Ding Yi , Abdulla Aynur , Li Yiyang , Jiang Lai , Ding Xianting 
Published: March 2024

AbstractSpatial proteomics elucidates cellular biochemical changes with unprecedented topological level. Imaging mass cytometry (IMC) is a high-dimensional single-cell resolution platform for targeted spatial proteomics. However, the precision of subsequent clinical analysis is constrained by imaging noise and resolution. Here, we propose SpiDe-Sr, a super-resolution network embedded with a denoising module for IMC spatial resolution enhancement. SpiDe-Sr effectively resists noise and improves resolution by 4 times. We demonstrate SpiDe-Sr respectively with cells, mouse and human tissues, resulting 18.95%/27.27%/21.16% increase in peak signal-to-noise ratio and 15.95%/31.63%/15.52% increase in cell extraction accuracy. We further apply SpiDe-Sr to study the tumor microenvironment of a 20-patient clinical breast cancer cohort with 269,556 single cells, and discover the invasion of Gram-negative bacteria is positively correlated with carcinogenesis markers and negatively correlated with immunological markers. Additionally, SpiDe-Sr is also compatible with fluorescence microscopy imaging, suggesting SpiDe-Sr an alternative tool for microscopy image super-resolution.
Mitochondrial H2O2 release does not directly cause damage to chromosomal DNA
Authors: van Soest Daan M. K. , Polderman Paulien E. , den Toom Wytze T. F. , Keijer Janneke P. , van Roosmalen Markus J. , Leyten Tim M. F. , Lehmann Johannes , Zwakenberg Susan , De Henau Sasha , van Boxtel Ruben , Burgering Boudewijn M. T. , Dansen Tobias B. 
Published: March 2024

AbstractReactive Oxygen Species (ROS) derived from mitochondrial respiration are frequently cited as a major source of chromosomal DNA mutations that contribute to cancer development and aging. However, experimental evidence showing that ROS released by mitochondria can directly damage nuclear DNA is largely lacking. In this study, we investigated the effects of H2O2 released by mitochondria or produced at the nucleosomes using a titratable chemogenetic approach. This enabled us to precisely investigate to what extent DNA damage occurs downstream of near- and supraphysiological amounts of localized H2O2. Nuclear H2O2 gives rise to DNA damage and mutations and a subsequent p53 dependent cell cycle arrest. Mitochondrial H2O2 release shows none of these effects, even at levels that are orders of magnitude higher than what mitochondria normally produce. We conclude that H2O2 released from mitochondria is unlikely to directly damage nuclear genomic DNA, limiting its contribution to oncogenic transformation and aging.
Pheromone-based communication influences the production of somatic extracellular vesicles in C. elegans
Authors: Szczepańska Agata , Olek Katarzyna , Kołodziejska Klaudia , Yu Jingfang , Ibrahim Abdulrahman Tudu , Adamkiewicz Laura , Schroeder Frank C. , Pokrzywa Wojciech , Turek Michał 
Published: March 2024

AbstractExtracellular vesicles (EVs) are integral to numerous biological processes, yet it is unclear how environmental factors or interactions among individuals within a population affect EV-regulated systems. In Caenorhabditis elegans, the evolutionarily conserved large EVs, known as exophers, are part of a maternal somatic tissue resource management system. Consequently, the offspring of individuals exhibiting active exopher biogenesis (exophergenesis) develop faster. Our research focuses on unraveling the complex inter-tissue and social dynamics that govern exophergenesis. We found that ascr#10, the primary male pheromone, enhances exopher production in hermaphrodites, mediated by the G-protein-coupled receptor STR-173 in ASK sensory neurons. In contrast, pheromone produced by other hermaphrodites, ascr#3, diminishes exophergenesis within the population. This process is regulated via the neuropeptides FLP-8 and FLP-21, which originate from the URX and AQR/PQR/URX neurons, respectively. Our results reveal a regulatory network that controls the production of somatic EV by the nervous system in response to social signals.
Architecture and activation of human muscle phosphorylase kinase
Authors: Yang Xiaoke , Zhu Mingqi , Lu Xue , Wang Yuxin , Xiao Junyu 
Published: March 2024

AbstractThe study of phosphorylase kinase (PhK)-regulated glycogen metabolism has contributed to the fundamental understanding of protein phosphorylation; however, the molecular mechanism of PhK remains poorly understood. Here we present the high-resolution cryo-electron microscopy structures of human muscle PhK. The 1.3-megadalton PhK α4β4γ4δ4 hexadecamer consists of a tetramer of tetramer, wherein four αβγδ modules are connected by the central β4 scaffold. The α- and β-subunits possess glucoamylase-like domains, but exhibit no detectable enzyme activities. The α-subunit serves as a bridge between the β-subunit and the γδ subcomplex, and facilitates the γ-subunit to adopt an autoinhibited state. Ca2+-free calmodulin (δ-subunit) binds to the γ-subunit in a compact conformation. Upon binding of Ca2+, a conformational change occurs, allowing for the de-inhibition of the γ-subunit through a spring-loaded mechanism. We also reveal an ADP-binding pocket in the β-subunit, which plays a role in allosterically enhancing PhK activity. These results provide molecular insights of this important kinase complex.
Addressing the effects of gas adsorption on monolayers beyond charge population analysis: the case of WS2
Authors: Bianchi Michele Giovanni , Risplendi Francesca , Re Fiorentin Michele , Cicero Giancarlo 
Published: March 2024

AbstractThe optoelectronic properties of two-dimensional (2D) materials can be significantly influenced by charge transfer resulting from surface molecular adsorption. One noteworthy example is observed in WS2 monolayers, where the behavior undergoes an anomalous change when exposed to air, primarily due to the adsorption of oxygen molecules. While the acceptor nature of O2 is widely acknowledged as the underlying cause, the precise electron transfer mechanism remains in need of a comprehensive explanation at the atomistic level. Going beyond conventional charge population analysis, we develop an approach describing the process of molecular adsorption and surface charge transfer that relies on the formalism commonly adopted for charged defects in semiconductors. This method clearly identifies two key factors contributing to electron transfer upon O2 physisorption: the presence of sulphur vacancies and the intrinsic n-type nature of WS2. This approach provides an effective and general scheme to characterize the surface charge transfer in 2D materials exposed to a gas atmosphere.
Association between irritable bowel syndrome and Parkinson’s disease by Cohort study and Mendelian randomization analysis
Authors: Wang Zhi-yun , Ma Dong-rui , Li Meng-jie , Liang Yuan-yuan , Hu Zheng-wei , Li Shuang-jie , Zuo Chun-yan , Hao Chen-wei , Feng Yan-mei , Guo Meng-nan , Hao Xiao-yan , Guo Yuan-li , Ma Ke-ke , Guo Li-na , Zhang Chan , Xu Yu-ming , Mao Cheng-yuan , Shi Chang-he 
Published: March 2024

AbstractThis study aimed to investigate the association between irritable bowel syndrome (IBS) and Parkinson’s disease (PD) utilizing prospective cohort study and Mendelian randomization. The dataset contained a substantial cohort of 426,911 participants from the UK Biobank, discussing the association between IBS and PD with Cox proportional hazards models and case-control analysis while adjusting for covariates such as age, gender, ethnicity and education level. In univariate Cox regression model, the risk of PD was reduced in IBS patients (HR: 0.774, 95%CI: 0.625–0.956, P = 0.017), but the statistical significance diminished in the three models after adjusting for other variables. In a few subgroup analyses, IBS patients are less likely to develop into PD, and patients diagnosed with IBS after 2000 also had a lower risk (HR: 0.633, 95%CI: 0.403–0.994, P = 0.047) of subsequently developing PD. In addition, we matched five healthy control participants based on gender and age at the end of the study for each IBS patient diagnosed during the follow-up period, and logistic regression results (OR:1.239, 95%CI: 0.896–1.680, P = 0.181) showed that IBS was not associated with the risk of PD. Mendelian randomization did not find significant evidence of the causal relationship between IBS and Parkinson’s disease (OR: 0.801, 95%CI: 0.570–1.278, P = 0.204). Overall, we suggest that IBS status is not associated with the risk of developing PD, and that these findings provide valuable insights into the clinical management and resource allocation of patients with IBS.
Ion-induced field screening as a dominant factor in perovskite solar cell operational stability
Authors: Thiesbrummel Jarla , Shah Sahil , Gutierrez-Partida Emilio , Zu Fengshuo , Peña-Camargo Francisco , Zeiske Stefan , Diekmann Jonas , Ye Fangyuan , Peters Karol P. , Brinkmann Kai O. , Caprioglio Pietro , Dasgupta Akash , Seo Seongrok , Adeleye Fatai A. , Warby Jonathan , Jeangros Quentin , Lang Felix , Zhang Shuo , Albrecht Steve , Riedl Thomas , Armin Ardalan , Neher Dieter , Koch Norbert , Wu Yongzhen , Le Corre Vincent M. , Snaith Henry , Stolterfoht Martin 
Published: March 2024

AbstractThe presence of mobile ions in metal halide perovskites has been shown to adversely affect the intrinsic stability of perovskite solar cells (PSCs). However, the actual contribution of mobile ions to the total degradation loss compared with other factors such as trap-assisted recombination remains poorly understood. Here we reveal that mobile ion-induced internal field screening is the dominant factor in the degradation of PSCs under operational conditions. The increased field screening leads to a decrease in the steady-state efficiency, often owing to a large reduction in the current density. Instead, the efficiency at high scan speeds (>1,000 V s−1), where the ions are immobilized, is much less affected. We also show that the bulk and interface quality do not degrade upon ageing, yet the open-circuit voltage decreases owing to an increase in the mobile ion density. This work reveals the importance of ionic losses for intrinsic PSC degradation before chemical or extrinsic mechanical effects manifest.
Crimean–Congo haemorrhagic fever virus uses LDLR to bind and enter host cells
Authors: Monteil Vanessa M. , Wright Shane C. , Dyczynski Matheus , Kellner Max J. , Appelberg Sofia , Platzer Sebastian W. , Ibrahim Ahmed , Kwon Hyesoo , Pittarokoilis Ioannis , Mirandola Mattia , Michlits Georg , Devignot Stephanie , Elder Elizabeth , Abdurahman Samir , Bereczky Sándor , Bagci Binnur , Youhanna Sonia , Aastrup Teodor , Lauschke Volker M. , Salata Cristiano , Elaldi Nazif , Weber Friedemann , Monserrat Nuria , Hawman David W. , Feldmann Heinz , Horn Moritz , Penninger Josef M. , Mirazimi Ali 
Published: March 2024

AbstractClimate change and population densities accelerated transmission of highly pathogenic viruses to humans, including the Crimean–Congo haemorrhagic fever virus (CCHFV). Here we report that the Low Density Lipoprotein Receptor (LDLR) is a critical receptor for CCHFV cell entry, playing a vital role in CCHFV infection in cell culture and blood vessel organoids. The interaction between CCHFV and LDLR is highly specific, with other members of the LDLR protein family failing to bind to or neutralize the virus. Biosensor experiments demonstrate that LDLR specifically binds the surface glycoproteins of CCHFV. Importantly, mice lacking LDLR exhibit a delay in CCHFV-induced disease. Furthermore, we identified the presence of Apolipoprotein E (ApoE) on CCHFV particles. Our findings highlight the essential role of LDLR in CCHFV infection, irrespective of ApoE presence, when the virus is produced in tick cells. This discovery holds profound implications for the development of future therapies against CCHFV.
Diving into the proteomic atlas of SARS-CoV-2 infected cells
Authors: Carregari Victor C. , Reis-de-Oliveira Guilherme , Crunfli Fernanda , Smith Bradley J. , de Souza Gabriela Fabiano , Muraro Stéfanie Primon , Saia-Cereda Veronica M. , Vendramini Pedro H. , Baldasso Paulo A. , Silva-Costa Lícia C. , Zuccoli Giuliana S. , Brandão-Teles Caroline , Antunes André , Valença Aline F. , Davanzo Gustavo G. , Virgillio-da-Silva João Victor , dos Reis Araújo Thiago , Guimarães Raphael Campos , Chaim Felipe David Mendonça , Chaim Elinton Adami , Kawagosi Onodera Carolina Mie , Ludwig Raissa Guimarães , Saccon Tatiana Dandolini , Damásio André R. L. , Leiria Luiz Osório S. , Vinolo Marco Aurélio R. , Farias Alessandro S. , Moraes-Vieira Pedro M. , Mori Marcelo A. , Módena José Luiz P. , Martins-de-Souza Daniel 
Published: March 2024

AbstractThe COVID-19 pandemic was initiated by the rapid spread of a SARS-CoV-2 strain. Though mainly classified as a respiratory disease, SARS-CoV-2 infects multiple tissues throughout the human body, leading to a wide range of symptoms in patients. To better understand how SARS-CoV-2 affects the proteome from cells with different ontologies, this work generated an infectome atlas of 9 cell models, including cells from brain, blood, digestive system, and adipocyte tissue. Our data shows that SARS-CoV-2 infection mainly trigger dysregulations on proteins related to cellular structure and energy metabolism. Despite these pivotal processes, heterogeneity of infection was also observed, highlighting many proteins and pathways uniquely dysregulated in one cell type or ontological group. These data have been made searchable online via a tool that will permit future submissions of proteomic data (https://reisdeoliveira.shinyapps.io/Infectome_App/) to enrich and expand this knowledgebase.
Overcoming radioresistance of breast cancer cells with MAP4K4 inhibitors
Authors: Kwon Yun-Suk , Lee Min-Gu , Kim Nam-Yi , Nam Gi Suk , Nam Kyung-Soo , Jang Hyunsoo , Kim Soyoung 
Published: March 2024

AbstractMitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) has recently emerged as a promising therapeutic target in cancer. In this study, we explored the biological function of MAP4K4 in radioresistant breast cancer cells using two MAP4K4 inhibitors, namely PF06260933 and GNE-495. Radioresistant SR and MR cells were established by exposing SK-BR-3 and MCF-7 breast cancer cells to 48–70 Gy of radiation delivered at 4–5 Gy twice a week over 10 months. Surprisingly, although radioresistant cells were derived from two different subtypes of breast cancer cell lines, MAP4K4 was significantly elevated regardless of subtype. Inhibition of MAP4K4 with PF06260933 or GNE-495 selectively targeted radioresistant cells and improved the response to irradiation. Furthermore, MAP4K4 inhibitors induced apoptosis through the accumulation of DNA damage by inhibiting DNA repair systems in radioresistant cells. Notably, Inhibition of MAP4K4 suppressed the expressions of ACSL4, suggesting that MAP4K4 functioned as an upstream effector of ACSL4. This study is the first to report that MAP4K4 plays a crucial role in mediating the radioresistance of breast cancer by acting upstream of ACSL4 to enhance DNA damage response and inhibit apoptosis. We hope that our findings provide a basis for the development of new drugs targeting MAP4K4 to overcome radioresistance.
Cyclosporine-induced kidney damage was halted by sitagliptin and hesperidin via increasing Nrf2 and suppressing TNF-α, NF-κB, and Bax
Authors: Abd-Eldayem Ahmed M. , Makram Sohayla Mahmoud , Messiha Basim Anwar Shehata , Abd-Elhafeez Hanan H. , Abdel-Reheim Mustafa Ahmed 
Published: March 2024

AbstractCyclosporine A (CsA) is employed for organ transplantation and autoimmune disorders. Nephrotoxicity is a serious side effect that hampers the therapeutic use of CsA. Hesperidin and sitagliptin were investigated for their antioxidant, anti-inflammatory, and tissue-protective properties. We aimed to investigate and compare the possible nephroprotective effects of hesperidin and sitagliptin. Male Wistar rats were utilized for induction of CsA nephrotoxicity (20 mg/kg/day, intraperitoneally for 7 days). Animals were treated with sitagliptin (10 mg/kg/day, orally for 14 days) or hesperidin (200 mg/kg/day, orally for 14 days). Blood urea, serum creatinine, albumin, cystatin-C (CYS-C), myeloperoxidase (MPO), and glucose were measured. The renal malondialdehyde (MDA), glutathione (GSH), catalase, and SOD were estimated. Renal TNF-α protein expression was evaluated. Histopathological examination and immunostaining study of Bax, Nrf-2, and NF-κB were performed. Sitagliptin or hesperidin attenuated CsA-mediated elevations of blood urea, serum creatinine, CYS-C, glucose, renal MDA, and MPO, and preserved the serum albumin, renal catalase, SOD, and GSH. They reduced the expressions of TNF-α, Bax, NF-κB, and pathological kidney damage. Nrf2 expression in the kidney was raised. Hesperidin or sitagliptin could protect the kidney against CsA through the mitigation of oxidative stress, apoptosis, and inflammation. Sitagliptin proved to be more beneficial than hesperidin.
Pr3+-doped YPO4 nanocrystal embedded into an optical fiber
Authors: Dorosz Dominik , Kochanowicz Marcin , Valiente Rafael , Diego-Rucabado Andrea , Rodríguez Fernando , Siñeriz-Niembro Nuria , Espeso José I. , Lesniak Magdalena , Miluski Piotr , Conzendorf Sylvia , Posseckardt Juliane , Liao Zhongquan , Jimenez Gloria Lesly , Müller Robert , Lorenz Martin , Schwuchow Anka , Leich Martin , Lorenz Adrian , Wondraczek Katrin , Jäger Matthias 
Published: March 2024

AbstractOptical fiber with YPO4:Pr3+ nanocrystals (NCs) is presented for the first time using the glass powder—NCs doping method. The method’s advantage is separate preparation of NCs and glass to preserve luminescent and optical properties of NCs once they are incorporated into optical fiber. The YPO4:Pr3+ nanocrystals were synthesized by the co-precipitation and hydrothermal methods, optimized for size (< 100 nm), shape, Pr3+ ions concentration (0.2 mol%), and emission lifetime. The core glass was selected from the non-silica P2O5-containing system with refractive index (n = 1.788) close to the NCs (no = 1.657, ne = 1.838). Optical fiber was drawn by modified powder-in-tube method after pre-sintering of glass powder—YPO4:Pr3+ (wt 3%) mixture to form optical fiber preform. Luminescent properties of YPO4:Pr3+ and optical fiber showed their excellent agreement, including sharp Pr3+ emission at 600 nm (1D2–3H4) and 1D2 level lifetime (τ = 156 ± 5 µs) under 488 nm excitation. The distribution of the YPO4:Pr3+ NCs in optical fiber were analyzed by TEM-EDS in the core region (FIB-SEM-prepared). The successful usage of glass powder—NCs doping method was discussed in the aspect of promising properties of the first YPO4:Pr3+ doped optical fiber as a new way to develop active materials for lasing applications, among others.
Reliable Tilt-depth estimates based on the stable computation of the tilt angle using robust vertical derivatives
Authors: Abdelrahman Kamal , Pham Luan Thanh , Oliveira Saulo Pomponet , Duong Van-Hao , Duy Thong Kieu , Gomez-Ortiz David , Fnais Mohammed S. , Eldosouky Ahmed M. 
Published: March 2024

AbstractThe Tilt-depth is a popular approach for determining depths of magnetic sources. As this method is based on the distance between contour levels of the tilt angle, it can lead to inaccurate depth estimates when the contour lines are distorted by the presence of noise. In this paper, we stabilize the Tilt-depth method based on the computation of stable vertical derivative obtained by the β-VDR method. The presented method is demonstrated on synthetic magnetic anomalies and real magnetic data from the Arabian Shield. The results obtained from the synthetic examples coincide well with the actual depths. These results proved the utility of the presented method in cases where the field is corrupted by noise. The real example shows that the presented method can provide valuable information on subsurface structures of the area where the Tilt-depth estimates are consistent with the result of the horizontal tilt angle. The findings show that the presented method is less sensitive to noise and can provide source edges and depths more clearly and with higher accuracy.
Fatty liver classification via risk controlled neural networks trained on grouped ultrasound image data
Authors: Yen Tso-Jung , Yang Chih-Ting , Lee Yi-Ju , Chen Chun-houh , Yang Hsin-Chou 
Published: March 2024

AbstractUltrasound imaging is a widely used technique for fatty liver diagnosis as it is practically affordable and can be quickly deployed by using suitable devices. When it is applied to a patient, multiple images of the targeted tissues are produced. We propose a machine learning model for fatty liver diagnosis from multiple ultrasound images. The machine learning model extracts features of the ultrasound images by using a pre-trained image encoder. It further produces a summary embedding on these features by using a graph neural network. The summary embedding is used as input for a classifier on fatty liver diagnosis. We train the machine learning model on a ultrasound image dataset collected by Taiwan Biobank. We also carry out risk control on the machine learning model using conformal prediction. Under the risk control procedure, the classifier can improve the results with high probabilistic guarantees.