bluuebunny/crossref_metadata_2025_split huggingface dataset:
The E3 ubiquitin ligase Nedd4 fosters developmental myelination in the mouse central and peripheral nervous system
Authors: Fimiani Cristina , Pereira Jorge A. , Gerber Joanne , Berg Ingrid , DeGeer Jonathan , Bachofner Sven , Fischer Jonas S. , Kauffmann Manuel , Suter Ueli 
Published: November 2024

AbstractUbiquitination is a major post‐translational regulatory mechanism that tunes numerous aspects of ubiquitinated target proteins, including localization, stability, and function. During differentiation and myelination, Oligodendrocytes (OLs) in the central nervous system and Schwann cells (SCs) in the peripheral nervous system undergo major cellular changes, including the tightly controlled production of large and accurate amounts of proteins and lipids. Such processes have been implied to depend on regulatory aspects of ubiquitination, with E3 ubiquitin ligases being generally involved in the selection of specific ubiquitination substrates by ligating ubiquitin to targets and granting target selectivity. In this study, we have used multiple transgenic mouse lines to investigate the functional impact of the E3 ubiquitin ligase Nedd4 in the OL‐ and SC‐lineages. Our findings in the developing spinal cord indicate that Nedd4 is required for the correct accumulation of differentiated OLs and ensures proper myelination, supporting and further expanding previously suggested conceptual models. In sciatic nerves, we found that Nedd4 is required for timely radial sorting of axons by SCs as a pre‐requirement for correct onset of myelination. Moreover, Nedd4 ensures correct myelin thickness in both SCs and spinal cord OLs.
Employment shocks and demand for pain medication: Understanding the channels that drive opioid use
Authors: Musse Isabel 
Published: November 2024

AbstractHigher employment ratios can affect opioid use through two main channels: by increasing physical pain from working or by reducing mental distress that may contribute to substance misuse. To separate these channels, I contrast the effect of labor demand shocks on the use of opioids with the effect on the use of over‐the‐counter painkillers—commonly used to treat pain but not mental distress. I find that during local economic expansions, opioid use declines while the demand for over‐the‐counter pain relief medication increases. Employment changes in high injury industries accentuate this pattern. One possible explanation is that, during local economic expansions, the use of pain medications to manage work injuries increases while the misuse of opioids decreases.
Radiation‐Induced Pharyngeal Necrosis and Cervical Spine Osteoradionecrosis in Patients With Oropharyngeal Squamous Cell Carcinoma
Authors: Shaari Diana S. , Kapustin Danielle A. , Yoon Michelle , Rubin Samuel J. , Khorsandi Azita , Ramirez Ricardo J. , Schiff Michael , Urken Mark L. 
Published: November 2024

ABSTRACTBackgroundRadiation therapy with or without chemotherapy is commonly used as an adjunct or alternative to surgery for treating head and neck cancer (HNC). In rare cases, radiation‐induced side effects such as posterior pharyngeal wall necrosis, fistula formation, and osteoradionecrosis (ORN) can lead to dangerous complications of the cervical spine (C‐spine).MethodsWe conducted a literature review on C‐spine ORN in HNC, and we reported four additional cases following the treatment of oropharyngeal carcinoma.ResultsWe identified 26 reported cases of C‐spine ORN following radiation for HNC. Of the four cases from our institution, two were treated with surgical management and two with conservative measures. Two patients were able to resume oral intake. The median time to diagnosis was 121.5 (range: 22–194) months after completion of radiation.ConclusionLate complications of radiation can be devastating, severely limiting functional status and quality of life. C‐spine ORN is related to total radiation dose and should be discussed with patients as a rare but serious side‐effect.
Antipsychotic‐Treated Schizophrenia Patients Develop Inflammatory and Oxidative Responses Independently From Obesity: However, Metabolic Disturbances Arise From Schizophrenia‐Related Obesity
Authors: Emre Sarandol , Asli Sarandol , Sener Mercan , Eker Salih Saygin , Esma Surmen‐Gur 
Published: November 2024

ABSTRACTObjectiveTo define the impact of obesity on inflammatory and oxidative disturbances in antipsychotic‐treated schizophrenia patients.MethodsSeveral cytokines, inflammatory, metabolic, and oxidative status markers were evaluated in obese (n = 40) and non‐obese (n = 40) antipsychotic‐treated patients and compared with age‐and BMI‐matched controls (n = 80).ResultsSchizophrenia patients had higher leptin, TNF‐α, adiponectin, visfatin, resistin, P‐selectin, NPY, BDNF, CD40‐L, MCP‐1, and malondialdehyde, and lower IL‐6, ghrelin, neopterin, and vitamin E levels compared to their respective controls (p < 0.001). Total oxidant status was higher in non‐obese patients compared to controls (p < 0.001), total antioxidant capacity was higher in obese compared to non‐obese patients (p < 0.01), but vitamin A and paraoxonase levels were not different. High sensitive‐CRP levels were higher in obsese controls relative to non‐obese controls (p < 0.05) and in obese patients relative to non‐obese patients (p < 0.001). Fasting glucose, insulin, HbA1c, HOMA‐IR, uric acid, total cholesterol, and triglyceride concentrations were higher in obese patients compared to non‐obese patients. Insulin concentrations and HOMA‐IR were also higher in obese controls than in non‐obese controls.ConclusionsOur results suggest that inflammatory responses and oxidative stress develop independently from obesity in antipsychotic‐treated schizophrenia patients. However, schizophrenia‐induced obesity causes metabolic disturbances; thereby, obese schizophrenia patients are more liable to cardiovascular events and progress of metabolic syndrome than non‐obese patients.
Hybrid Wavelet‐Deep Learning Framework for Fluorescence Microscopy Images Enhancement
Authors: Branciforti Francesco , Maggiore Maura , Meiburger Kristen M. , Pannellini Tania , Salvi Massimo 
Published: November 2024

ABSTRACTFluorescence microscopy is a powerful tool for visualizing cellular structures, but it faces challenges such as noise, low contrast, and autofluorescence that can hinder accurate image analysis. To address these limitations, we propose a novel hybrid image enhancement method that combines wavelet‐based denoising, linear contrast enhancement, and convolutional neural network‐based autofluorescence correction. Our automated method employs Haar wavelet transform for noise reduction and a series of adaptive linear transformations for pixel value adjustment, effectively enhancing image quality while preserving crucial details. Furthermore, we introduce a semantic segmentation approach using CNNs to identify and correct autofluorescence in cellular aggregates, enabling targeted mitigation of unwanted background signals. We validate our method using quantitative metrics, such as signal‐to‐noise ratio (SNR) and peak signal‐to‐noise ratio (PSNR), demonstrating superior performance compared to both mathematical and deep learning‐based techniques. Our method achieves an average SNR improvement of 8.5 dB and a PSNR increase of 4.2 dB compared with the original images, outperforming state‐of‐the‐art methods such as BM3D and CLAHE. Extensive testing on diverse datasets, including publicly available human‐derived cardiosphere and fluorescence microscopy images of bovine endothelial cells stained for mitochondria and actin filaments, showcases the flexibility and robustness of our approach across various acquisition conditions and artifacts. The proposed method significantly improves fluorescence microscopy image quality, facilitating more accurate and reliable analysis of cellular structures and processes, with potential applications in biomedical research and clinical diagnostics.
Mobilization and Apheresis Collection Strategies to Reduce Platelet Loss in G‐CSF Mobilized Healthy Adult Donors
Authors: Castro Brittany , Huang Jane , Le Julie , Pascua Diana , Goto Hirona , Kirby Denise , Lin David 
Published: November 2024

ABSTRACTGranulocyte‐colony stimulating factor (G‐CSF) mobilizes hematopoietic progenitor cells (HPC) into the peripheral blood. Donor peripheral blood platelet loss has been observed during both G‐CSF mobilization and apheresis collection. This study evaluates two strategies to reduce donor platelet loss, preserve product CD34+ cell yield and collection efficiency and increase volume of whole blood (WB) processed. One hundred and two adults healthy donors were mobilized with either standard dose G‐CSF (9.5–12 mcg/kg/day × 4 days) or lower dose G‐CSF (7.5–10 mcg/kg/day × 4 days) according to their pre‐mobilization platelet count. Apheresis centrifugal force was adjusted by lowering the packing factor (PF) setting on the apheresis instrument. Between‐group differences were observed in absolute donor platelet loss (p = 0.04) favoring lower G‐CSF dosing, while percent donor platelet loss trended towards significance (p = 0.10). Lowering PF from the manufacturer's default of 4.5 to 4.0 demonstrated between‐group differences in absolute donor platelet loss (p < 0.05), percent donor platelet loss (p < 0.001), and apheresis product platelet content (p < 0.001). No differences were observed in the product CD34+ cell content and CD34+ cell collection efficiency when PF was reduced to 4.0. Additionally, a higher volume of WB could be processed due to reduced donor platelet loss. Together, these two strategies may mitigate the risk of cumulative platelet loss in G‐CSF mobilized healthy donors undergoing apheresis collection, thereby increasing the likelihood of completing the target total blood volume to be processed while maintaining donor safety.
Therapeutic Plasma Exchange Management for a Pediatric Patient Presenting With Immune Thrombotic Thrombocytopenic Purpura in a Setting of Common Variable Immunodeficiency
Authors: Budhipramono Albert , Sharma Ruchika , Wysocki Christian Allen , Zia Ayesha N. , Adkins Brian D. 
Published: November 2024

ABSTRACTCommon variable immunodeficiency (CVID) is a disorder characterized by hypogammaglobulinemia resulting in recurrent infections. While autoimmune disorders are common in patients with CVID, no association has been reported between CVID and immune thrombotic thrombocytopenic purpura (iTTP), a disorder most often caused by autoantibodies that compromise the activity of the enzyme ADAMTS13. Reduced ADAMTS13 activity results in the accumulation of large von Willebrand factor multimers that can consume platelets and cause microvascular thrombosis and organ injury, ultimately resulting in mortality in most cases of untreated iTTP. Here, we report a 12‐year‐old male with CVID who developed iTTP, underwent therapeutic plasma exchange (TPE), and subsequently recovered. We conducted a systematic review for other cases of CVID co‐occurring with iTTP and present additional cases of this rare presentation. We highlight the importance of prompt recognition of iTTP in a patient with CVID and timely initiation of TPE.
Phosphine‐mediated one‐pot reactions: Syntheses of β‐acylated alkylidene indandiones and furo[2,3‐f]dibenzotropones via MBH‐type annulation/acylation or Wittig reaction
Authors: Chien Po‐Chung , Chen You‐Jie , Marri Gangababu , Chen Yi‐Ru , Chang Ching‐Fen , Wu Pei‐Shan , Lin Wenwei 
Published: November 2024

AbstractPhosphine‐mediated one‐pot reactions have been developed that involve two mechanistically distinct reactions assembled in one reaction vessel via the sequential addition process. The first step involves MBH‐type annulation of α,β‐ynones to afford cyclic products in each case, which then engages in subsequent β‐acylation or intramolecular Wittig reactions. The reaction conditions are mild and efficient, providing acylated alkylidene indandiones in 70%–99% yields or furo[2,3‐f]dibenzotropones in 65%–91% yields, respectively.
Dynamic mRNA Stability Buffer Transcriptional Activation During Neuronal Differentiation and Is Regulated by SAMD4A
Authors: Zhou Yuan , Rashad Sherif , Ando Daisuke , Kobayashi Yuki , Tominaga Teiji , Niizuma Kuniyasu 
Published: November 2024

ABSTRACTNeurons are exceptionally sensitive to oxidative stress, which is the basis for many neurodegenerative disease pathophysiologies. The posttranscriptional basis for neuronal differentiation and behavior is not well characterized. The steady‐state levels of mRNA are outcomes of an interplay between RNA transcription and decay. However, the correlation between mRNA transcription, translation, and stability remains elusive. We utilized a SH‐SY5Y‐based neural differentiation model that is widely used to study neurodegenerative diseases. After neuronal differentiation, we observed enhanced sensitivity of mature neurons to mitochondrial stresses and ferroptosis induction. We employed a newly developed simplified mRNA stability profiling technique to explore the role of mRNA stability in SH‐SY5Y neuronal differentiation model. Transcriptome‐wide mRNA stability analysis revealed neural‐specific RNA stability kinetics. Our analysis revealed that mRNA stability could either exert the buffering effect on gene products or change in the same direction as transcription. Importantly, we observed that changes in mRNA stability corrected over or under transcription of mRNAs to maintain mRNA translation dynamics. Furthermore, we conducted integrative analysis of our mRNA stability data set, and a published CRISPR‐i screen focused on neuronal oxidative stress responses. Our analysis unveiled novel neuronal stress response genes that were not evident at the transcriptional or translational levels. SEPHS2 emerged as an important neuronal stress regulator based on this integrative analysis. Motif analysis unveiled SAMD4A as a major regulator of the dynamic changes in mRNA stability observed during differentiation. Knockdown of SAMD4A impaired neuronal differentiation and influenced the response to oxidative stress. Mechanistically, SAMD4A was found to alter the stability of several mRNAs. The novel insights into the interplay between mRNA stability and cellular behaviors provide a foundation for understanding neurodevelopmental processes and neurodegenerative disorders and highlight dynamic mRNA stability as an important layer of gene expression.
An Artificial Intelligence Approach for Test‐Free Identification of Sarcopenia
Authors: Yin Liangyu , Zhao Jinghong 
Published: November 2024

ABSTRACTBackgroundThe diagnosis of sarcopenia relies extensively on human and equipment resources and requires individuals to personally visit medical institutions. The objective of this study was to develop a test‐free, self‐assessable approach to identify sarcopenia by utilizing artificial intelligence techniques and representative real‐world data.MethodsThis multicentre study enrolled 11 661 middle‐aged and older adults from a national survey initialized in 2011. Follow‐up data from the baseline cohort collected in 2013 (n = 9403) and 2015 (n = 10 356) were used for validation. Sarcopenia was retrospectively diagnosed using the Asian Working Group for Sarcopenia 2019 framework. Baseline age, sex, height, weight and 20 functional capacity (FC)–related binary indices (activities of daily living = 6, instrumental activities of daily living = 5 and other FC indices = 9) were considered as predictors. Multiple machine learning (ML) models were trained and cross‐validated using 70% of the baseline data to predict sarcopenia. The remaining 30% of the baseline data, along with two follow‐up datasets (n = 9403 and n = 10 356, respectively), were used to assess model performance.ResultsThe study included 5634 men and 6027 women (median age = 57.0 years). Sarcopenia was identified in 1288 (11.0%) individuals. Among the 20 FC indices, the running/jogging 1 km item showed the highest predictive value for sarcopenia (AUC [95%CI] = 0.633 [0.620–0.647]). From the various ML models assessed, a 24‐variable gradient boosting classifier (GBC) model was selected. This GBC model demonstrated favourable performance in predicting sarcopenia in the holdout data (AUC [95%CI] = 0.831 [0.808–0.853], accuracy = 0.889, recall = 0.441, precision = 0.475, F1 score = 0.458, Kappa = 0.396 and Matthews correlation coefficient = 0.396). Further model validation on the temporal scale using two longitudinal datasets also demonstrated good performance (AUC [95%CI]: 0.833 [0.818–0.848] and 0.852 [0.840–0.865], respectively). The model's built‐in feature importance ranking and the SHapley Additive exPlanations method revealed that lifting 5 kg and running/jogging 1 km were relatively important variables among the 20 FC items contributing to the model's predictive capacity, respectively. The calibration curve of the model indicated good agreement between predictions and actual observations (Hosmer and Lemeshow p = 0.501, 0.451 and 0.374 for the three test sets, respectively), and decision curve analysis supported its clinical usefulness. The model was implemented as an online web application and exported as a deployable binary file, allowing for flexible, individualized risk assessment.ConclusionsWe developed an artificial intelligence model that can assist in the identification of sarcopenia, particularly in settings lacking the necessary resources for a comprehensive diagnosis. These findings offer potential for improving decision‐making and facilitating the development of novel management strategies of sarcopenia.
Phytoremediation of soil co‐contaminated with uranium and chromium by sunflower (Helianthus annuus L.) enhanced with slow‐release composite chelating agent (EDTA/ammonium citrate)
Authors: Lin Zixin , Wang Guanghui , Zhou Zhongkui , Deng Nansheng , Zhang Xuewen 
Published: November 2024

AbstractBACKGROUNDSoil in uranium mining areas is contaminated by uranium and associated heavy metals, posing a significant threat to human health and ecological security. Chelating agent assisted phytoremediation is a cost‐effective and ecologically friendly remediation approach for uranium and associated heavy metals contaminated soil. In this work, a novel slow‐release composite chelating agent (SRCMC‐g‐CMCD‐EDTA/AC) was fabricated using carboxymethyl chitosan‐graft‐carboxymethyl‐β‐cyclodextrin (CMC‐g‐CMCD) as a slow‐release carrier and EDTA/ammonium citrate (AC) as a composite chelating agent through the spray drying method, which was used for phytoremediation of soil co‐contaminated with uranium and chromium.RESULTSCMC‐g‐CMCD exhibited superior slow‐release performance for both EDTA and AC in comparison with CMC and CMCD. When applied to soil contaminated with uranium (U) and chromium (Cr), SRCMC‐g‐CMCD‐EDTA/AC effectively regulated the release of U and Cr. Sunflowers (Helianthus annuus L.) grown in treated soil showed a significant increase in U and Cr uptake by 70.55% and 35.55%, respectively, and reduced leaching losses by 34.88% and 37.42%.CONCLUSIONSRCMC‐g‐CMCD‐EDTA/AC not only assists in the phytoremediation of soil co‐contaminated with U and Cr but also reduces the risk of leaching into groundwater during the soil phytoremediation process. SRCMC‐g‐CMCD‐EDTA/AC‐assisted phytoremediation technology was an effective and environmentally friendly remediation means for the removal of U and heavy metals from contaminated soils in uranium mining areas. © 2024 Society of Chemical Industry (SCI).
Prevalence of Chronic Liver Disease Based on Ultrasound Shear Wave Elastography in an Adult Asian Indian Population Attending Outpatient Preventive Radiology Clinics in India
Authors: Choorakuttil Rijo M. , Chaubal Rajas N. , Pratap Thara , Arunachalam Venkatesh K. , Kumar S. Harish , Bagri Neha , Gupta Anjali , Chelladurai Amarnath , Nirmalan Praveen K. 
Published: November 2024

ABSTRACTAimTo determine the ultrasound shear wave elastography (SWE)‐based prevalence of chronic liver disease in an adult Asian Indian population attending preventive radiology outpatient clinics in India.MethodsLiver stiffness measures (LSMs) were ascertained using ultrasound SWE and interquartile range/median (IQR/M) ratio ≤ 30% kilopascal (kPa) units were considered a good quality measurement. Details of modifiable risk factors including comorbidity and personal risk behaviors were collected. The liver was graded based on the Society of Radiologists in Ultrasound Liver Elastography Consensus Statement and Grades 4 and 5 indicated compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH). A multivariate logistic regression model was used to analyze associations with chronic advanced liver disease.ResultsThe median LSM in the study participants (n = 1145) was 8.0 (IQR 6.5, 9.85) kPa units. 10.65% of the study population had advanced chronic liver disease (cACLD and CSPH) and 22.79% had LSM that was suggestive of cACLD. cACLD and CSPH were significantly associated with comorbidities, personal risk behaviors, and lean and obese body mass indices. Modifiable risk factors were present in 20%–50% of participants with LSM between 7 and 13 kPa.ConclusionInformation on the prevalence of LSM‐based cACLD and CSPH and modifiable risk factors in persons with LSM between 7 and 13 kPa will help to design preventative strategies using LSM as an objective imaging biomarker.
Challenging the conventional wisdom: Re‐evaluating Smpd3's role in extracellular vesicle biogenesis
Authors: Burgelman Marlies , Dujardin Pieter , Willems Anthony , Hochepied Tino , Van Imschoot Griet , Van Wonterghem Elien , Van Hoecke Lien , Vandendriessche Charysse , Vandenbroucke Roosmarijn E. 
Published: November 2024

AbstractExtracellular vesicles (EVs) are pivotal in intercellular communication, impacting diverse physiological and pathological processes. Current in vitro EV biogenesis studies often utilize pharmacological inhibitors, inducing off‐target effects and overlooking cell‐specific production nuances. Addressing these limitations, we utilized CRISPR/Cas9 to generate heterozygous full‐body and conditional sphingomyelin phosphodiesterase 3 (Smpd3) knockout (KO) transgenic mice. Smpd3, also known as neutral sphingomyelinase 2 (nSMase2), triggers membrane curvature through sphingomyelin hydrolysis to ceramide, thereby influencing exosome release. Intriguingly, Smpd3 deficiency demonstrated no impact on EV release both in vitro and in vivo, underscoring its potential cell‐type‐specific role in EV biogenesis. Notably, bone marrow derived macrophages (BMDMs) did exhibit reduced EV release upon Alix deletion. Our findings open avenues for subsequent inquiries, enriching our knowledge of EV biogenesis and illuminating intercellular communication in health and disease.