bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuronal Detection Triggers Systemic Digestive Shutdown in Response to Adverse Food Sources
Authors: Liu Yating , Tian Guojing , Wang Ziyi , Zheng Junkang , Liu Huimin , Zhu Sucheng , Shan Zhao , Qi Bin 
Published: November 2024

SummaryThe ability to sense and adapt to adverse food conditions is essential for survival across species, but the detailed mechanisms of neuron-digestive crosstalk in food sensing and adaptation remain poorly understood. This study identifies a novel mechanism by which animals detect unfavorable food sources through olfactory neurons and initiate a systemic response to shut down digestion, thus safeguarding against potential harm. Specifically, we demonstrate that NSY-1, expressed in AWC olfactory neurons, detectsStaphylococcus saprophyticus(SS) as an unfavorable food source, prompting the animal to avoid and halt digestion of SS. Upon detection, the animals activate the AWCOFFneural circuit, leading to a systemic digestive shutdown, which is mediated by NSY-1-dependent STR-130. Additionally, NSY-1 mutation triggers the production of insulin peptides, including INS-23, which interact with the DAF-2 receptor to modulate SS digestion and affects the expression of intestinal BCF-1. These findings uncover a crucial survival strategy through neuron-digestive crosstalk, where the NSY-1 pathway in AWC neurons orchestrates food evaluation and initiates digestive shutdown to adapt effectively to harmful food sources.
Global analysis by LC-MS/MS ofN6-methyladenosine and inosine in mRNA reveal complex incidence
Authors: Stejskal Stanislav , Rájecká Veronika , Covelo-Molares Helena , Sinigaglia Ketty , Brožinová Květoslava , Kasiarova Linda , Dohnálková Michaela , Reyes-Gutierrez Paul Eduardo , Cahová Hana , Keegan Liam P. , O’Connell Mary A. , Vanacova Stepanka 
Published: November 2024

AbstractThe precise and unambiguous detection and quantification of internal RNA modifications represents a critical step for understanding their physiological functions. The methods of direct RNA sequencing are quickly developing allowing for the precise location of internal RNA marks. This detection is however not quantitative and still presents detection limits. One of the biggest remaining challenges in the field is still the detection and quantification of m6A, m6Amand m1A modifications. The second intriguing and timely question remaining to be addressed is the extent to which individual marks are coregulated or potentially can affect each other. Here we present a methodological approach to detect and quantify several key mRNA modifications in human total RNA and in mRNA, which is difficult to purify way from contaminating tRNA. We show that the adenosine demethylase FTO primarily targets m6Ammarks in noncoding RNAs in HEK293T cells. Surprisingly, we observe little effect of FTO or ALKBH5 depletion on the m6A mRNA levels. Interestingly, upregulation of ALKBH5 is accompanied by an increase in inosine level in overall mRNA.
Assessing Language Difficulties in Health Facilities in Malawi
Authors: Taylor Amelia , Kazembe Paul 
Published: November 2024

AbstractLanguage barriers in healthcare, prevalent globally, often lead to miscommunication between professionals and patients, reducing the quality of care. Recognition, training, and formal study of these barriers during medical communication in African countries is severely limited. Our study focused on language barriers in healthcare facilities in Zomba, an important district in Malawi where several local languages are spoken. We employed a qualitative approach and conducted a questionnaire-based study. Data was gathered from 79 healthcare professionals and 312 patients. Our findings show that a lack of language preparation during health training and the absence of suitable resources in local languages, such as dictionaries, result in healthcare professionals struggling to communicate with patients in both English and local languages about medical issues. Patients also face difficulties in fully conveying their symptoms and understanding their diagnoses or treatments due to language barriers. We conclude that language training and health dictionaries in both English and local languages can help address some of these observed language barriers.
Diagnosis Of Satoyoshi Syndrome Using A Neuroblastoma Cell (SH-SY5Y) Lysate As Substrate For Western Blot
Authors: Sevilla Avendaño José María , Garrido Carlos , Rodríguez Clemente Irene , Solís-García del Pozo Julián , Stephani Ulrich , Martínez Ricardo , Matsuura Eiji , de Cabo Carlos , Ceña Valentín , Solera Javier 
Published: November 2024

ABSTRACTObjectiveSatoyoshi syndrome is a rare, likely autoimmune disorder that is traditionally diagnosed based on clinical criteria: painful muscle spasms, diarrhea and alopecia. Two previous reports showed a specific immunoreactive band in three patients using Western blot analysis with brain homogenate. The aim of this study was to evaluate the efficacy of SH-SY5Y cell lysate as a potential substitute for brain homogenate in the diagnosis of Satoyoshi syndrome.MethodsWestern blot analyses were conducted using brain homogenate, SH-SY5Y cell lysates, and differentiated SH-SY5Y cell lysates. Serum samples were obtained from three patients diagnosed with Satoyoshi syndrome, alongside control samples from thirty blood donors and six patients with other neurological conditions.ResultsSera from patients with Satoyoshi syndrome displayed a consistent three band pattern in the 70–100 kDa range. This pattern was reproducible across all tested substrates (brain homogenate, SH-SY5Y lysate, and differentiated SH-SY5Y lysate), but it was not observed for the sera from the control groups. The immunoreactive bands were more patent when using either SH-SY5Y lysate compared to brain homogenate. No differences were found between the SH-SY5Y lysate and differentiated SH-SY5Y lysate.ConclusionSH-SY5Y cell lysate could be an alternative to brain homogenate for the immunodiagnostic evaluation of Satoyoshi syndrome. The use of SH-SY5Y cell lysate for Western blot analysis may improve visualization and reproducibility and have a lower cost.Key messagesSatoyoshi syndrome is a rare disease currently diagnosed based only on clinical criteriaA biological marker test for Satoyoshi syndrome could lead to early diagnosis and treatment thus improving the outcomes.SH-SY5Y cell lysate may be a better substrate than brain homogenate for Western blot based diagnosis of Satoyoshi syndrome.
Relationship between plasma cortisol concentration and Long COVID symptoms in the post-acute phase of COVID-19: a cross-sectional study and recommendations for future research
Authors: Dalhuisen Thomas , Grebe Halle , Anglin Khamal , Lu Scott , Goldberg Sarah A. , Kallás-Silva Lucas , Hauser Joshua , Conway Emily , Ewing Marin , Chen Jessica Y. , Fehrman Emily A. , Kelly J. Daniel , Martin Jeffrey N. , Hunt Peter W. , Henrich Timothy J. , Durstenfeld Matthew S. , Deeks Steven G. , Murphy Elizabeth , Schambelan Morris , Peluso Michael J. 
Published: November 2024

ABSTRACTBACKGROUNDLow cortisol concentrations have been reported in some people with Long COVID (LC), but more data from diverse cohorts are needed to validate this observation. A subset of people with LC present with symptoms resembling those of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The objective of this study was to compare cortisol concentrations in those with and without Long COVID, with a particular focus on people experiencing ME/CFS-like Long COVID.METHODSWe measured plasma cortisol in 200 individuals 3-6 months following a SARS-CoV-2 infection. Banked biospecimens collected between 8 AM-12 PM were used. Participants met the case definition for Long COVID if they had ≥1 COVID-attributed symptom at least 3 months after symptom onset. People who did not report any symptoms at least 3 months after symptom onset served as recovered controls. Adapting the 2015 Institute of Medicine criteria for ME/CFS, we further defined those with LC resembling ME/CFS (LC-ME).RESULTSWe found no difference in overall morning cortisol concentrations between people with LC (n=144) and those who fully recovered (n=56) (median 8.9 µg/dL vs. 8.8 µg/dL, p=0.97). Analyses of samples collected between 8-10 AM, however, revealed that, compared to those who fully recovered, cortisol concentrations were lower between 8-9 AM for those with LC-ME (median 8.2 vs. 14.8, p=0.02), but higher between 9-10 AM for those with severe LC (>=5 symptoms) (median 12.4 vs. 8.5, p=0.009) and those with LC-ME (median 13.7 vs. 8.5, p=0.02).CONCLUSIONWe found no difference in overall morning plasma cortisol concentrations between those with and without Long COVID. Although our data could be suggestive of altered morning cortisol dynamics in a subset of people with Long COVID, longitudinal measures of cortisol in individuals with Long COVID will be critical to further inform the biology of the condition.
Subthalamic Nucleus Deep Brain Stimulation Modulates Strabismus in Parkinson’s Disease
Authors: Gupta Palak , Beylergil Sinem Balta , Kilbane Camilla , McIntyre Cameron C. , Noecker Angela M , Shaikh Aasef G. , Ghasia Fatema F. 
Published: November 2024

AbstractObjectiveParkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms. Visual impairments, such as strabismus (misalignment of the eyes during gaze holding), affect up to two-thirds of PD patients, impacting their quality of life. Conventional treatments offer limited relief, prompting exploration of alternatives like deep brain stimulation (DBS) of subthalamic nucleus (STN). This pilot study aims to assess whether STN DBS can alleviate PD-related strabismus and identify specific STN regions associated with favorable outcomes. We hypothesize that STN DBS improves strabismus by modulating subthalamic connectivity with the cerebellum, hence volume of activate tissue (VTA) generated with DBS will be in dorsal STN.MethodsWe studied 12 PD patients with bilateral STN DBS and five healthy controls. Clinical assessments, eye movement measurements using high-resolution eye tracking, and patient-specific DBS models were employed. Analysis included the VTA models, revealing distinct effects based on the location within the STN.ResultsWe found significant strabismus in 66% of PD patients. STN DBS improved strabismus in 75% of cases. The improvement was associated with dorsal STN stimulation. STN DBS exacerbated strabismus in 25% of PD patients. The VTA in these participants were located in the ventral aspect of the STN.DiscussionThe findings highlight the significant effects of STN DBS on strabismus in PD, further offering insights into the complex interplay between neurodegeneration and control of eye alignment. This approach, combining clinical assessments, advanced eye tracking, and DBS computational modeling, contributes valuable knowledge towards targeted interventions for visual impairments in PD.
Deep Learning Unlocks the True Potential of Organ Donation after Circulatory Death with Accurate Prediction of Time-to-Death
Authors: Sun Xingzhi , De Brouwer Edward , Liu Chen , Krishnaswamy Smita , Batra Ramesh 
Published: November 2024

ABSTRACTIncreasing the number of organ donations after circulatory death (DCD) has been identified as one of the most important ways of addressing the ongoing organ shortage. While recent technological advances in organ transplantation have increased their success rate, a substantial challenge in increasing the number of DCD donations resides in the uncertainty regarding the timing of cardiac death after terminal extubation, impacting the risk of prolonged ischemic organ injury, and negatively affecting post-transplant outcomes. In this study, we trained and externally validated an ODE-RNN model, which combines recurrent neural network with neural ordinary equations and excels in processing irregularly-sampled time series data. The model is designed to predict time-to-death following terminal extubation in the intensive care unit (ICU) using the last 24 hours of clinical observations. Our model was trained on a cohort of 3,238 patients from Yale New Haven Hospital, and validated on an external cohort of 1,908 patients from six hospitals across Connecticut. The model achieved accuracies of 95.3 ± 1.0% and 95.4 ± 0.7% for predicting whether death would occur in the first 30 and 60 minutes, respectively, with a calibration error of 0.024 ± 0.009. Heart rate, respiratory rate, mean arterial blood pressure (MAP), oxygen saturation (SpO2), and Glasgow Coma Scale (GCS) scores were identified as the most important predictors. Surpassing existing clinical scores, our model sets the stage for reduced organ acquisition costs and improved post-transplant outcomes.
Exploratory Blood Biomarker Patterns in a Mixed Dementia Cohort
Authors: Gezegen Haşim , Alaylıoğlu Merve , Şahin Erdi , Swann Owen , Veleva Elena , Güven Gamze , Yaman Umran , Salih Derviş A. , Bilgiç Başar , Hanağası Haşmet , Gürvit Hakan , Emre Murat , Gezen-Ak Duygu , Dursun Erdinç , Zetterberg Henrik , Hardy John , Heslegrave Amanda , Shoai Maryam , Samancı Bedia 
Published: November 2024

AbstractAlzheimer’s disease (AD) diagnosis is challenging due to overlapping symptoms with other dementias. Current diagnostic methods are invasive and costly, highlighting the need for accessible biomarkers. This study investigates the diagnostic performance and pathophysiological implications of a novel plasma biomarker panel in a mixed dementia cohort, aiming to enhance diagnosis and elucidate underlying pathogenic mechanisms.120 plasma biomarkers were analyzed using the NULISA™ platform in a well-characterized mixt dementia. CSF biomarkers were measured via ELISA. Statistical analyses employed ANOVA, and Kruskal-Wallis tests for group comparisons. Spearman correlations assessed relationships between CSF and plasma biomarkers. Diagnostic accuracy was evaluated using regression models and ROC curves. Feature importance and selection were performed using random forest analysis. Protein interactions assessed with GO enrichment analysis.We evaluated 248 subjects (130 females, 118 males) with 117 AD, 50 MCI, 39 FTD, 25 DLB, and 17 other dementias. Plasma pTau were significantly elevated in AD compared to other groups, and in DLB compared to MCI. Plasma Aβ42 was highest in DLB, while NfL was highest in FTD. Plasma GFAP was highest in AD and elevated in DLB compared to MCI and FTD.Plasma pTau levels showed a negative correlation with CSF Aβ42 and a positive correlation with CSF pTau in the entire cohort. CSF and plasma NfL levels were also highly correlated. These correlations were stronger in DLB and amyloid-positive MCI groups but weaker or absent in the AD group. Plasma pTau, GFAP, and NfL were negatively correlated with MMSE in AD, while GFAP showed a negative correlation with MMSE in FTD and DLB.Plasma pTau217 demonstrated the best diagnostic accuracy for AD, DLB, FTD diagnosis and CSF amyloid positivity (AUCs 0.9, 0.84, 0.79, and 0.87, respectively). pTau181, pTau217, pTau231, total-tau and GFAP had lower odds in DLB and FTD compared to AD. AGRN, CXCL1, SCNB, TEK, and UCHL1 had higher odds in DLB compared to AD. SNAP25 had lower odds ratio in FTD compared to AD and DLB. pTau181, pTau217, pTau231, GFAP, MAPT, SNAP25 and PGF is related to AD progression.Random forest analysis incorporating all plasma biomarkers, age, and gender yielded an AUCs of 0.85 for AD, 0.84 for FTD, and 0.75 for DLB. Refining the model by including biomarkers identified as significant in regression model improved performance, resulting in AUCs of 0.88 for AD, 0.87 for FTD, and 0.81 for DLB. This demonstrates potential for enhancing diagnostic accuracy through targeted biomarker panel refinement.
ELABELA as a Potential Diagnostic Biomarker and Therapeutic Target of Atherosclerosis
Authors: Tang Le , Yi Xiaoli , Yang Huiru , Song Shanshan , Tan Wenting , Xiong Jianhua , Liu Chunju , Zhang Yifeng , Wang Mulan , Zhu Mengzhi , Zheng Lixiang , Yu Jun , Xu Chuanming 
Published: November 2024

AbstractAtherosclerosis (AS) is a progressive arterial disease characterized by chronic inflammation and plaque formation in blood vessel walls. ELABELA, an endogenous ligand for the G protein-coupled receptor APJ (apelin peptide jejunum, apelin receptor), has multiple pharmacological activities for protecting the cardiovascular system. This study aimed to determine the potential anti-atherosclerotic effect of ELABELA and reveal the underlying mechanisms. Plasma ELABELA levels were significantly reduced and negatively correlated with plasma MMP2 and MMP9 levels in AS patients and high-fat diet-induced atheroscleroticApoE−/−mice. Plasma ELABELA levels exhibited a potential diagnostic value for AS patients. Application of ELABELA-21 (ELA-21) significantly decreased atherosclerotic plaque area and inflammation in the aortas from theApoE-/-mice. ELA-21 administration modulated the balance between M1 and M2 macrophages in the abdominal cavity and aorta roots toward a more anti-inflammatory status, accompanied by reduced MMP2, MMP9, and PRR and enhanced APJ, ACE, and ACE2 protein expression in plaques within aortic roots and decreased plasma sPRR levels.In vitro, ELA-21 effectively suppressed oxidized-low-density lipoprotein-induced foam cell formation and LPS/IFN-γ-induced M1 polarization in THP-1 cells. Interestingly, the anti-inflammatory effect of ELA-21 was further enhanced by APJ inhibitor ML221, accompanied by elevatedACEandATP6AP2and reducedACE2mRNA levels. Collectively, our data highlighted the diagnostic and therapeutic potential of ELABELA on AS. ELA-21 protects against AS by inhibiting atherosclerotic plaque formation and promoting a more stable plaque phenotype, possibly via restoring the M1/M2 macrophage balance, enhancing macrophage ACE and ACE2 expression, and inhibiting the PRR system. ELABELA may be a novel biomarker and candidate therapeutic target for treating AS.
Variable-Interval Temporal Feathering to Optimize Organ-at-Risk Repair for Head and Neck Adaptive Radiotherapy
Authors: Karagoz Aysenur , Hemmati Mehdi , Nosrat Fatemeh , Mavroidis Panayiotis , Dede Cem , McCullum Lucas B. , Garcia Raul , Hosseinian Seyedmohammadhossein , Scott Jacob G. , Bates James E. , Enderling Heiko , Mohamed Abdallah S.R. , Brock Kristy K. , Schaefer Andrew J. , Fuller Clifton D. 
Published: November 2024

AbstractPurposeTemporally feathered radiation therapy (TFRT) for head-and-neck cancer (HNC) radiotherapy combines variable-dose daily subplans to increase the rest time of organs-at-risk (OARs) as sought in intensity modulated radiation therapy (IMRT). While the standard TFRT recommends uniform rest time for each OAR, improved toxicity outcomes may be achieved through variable rest time for OARs by incorporating the OARs’ variable radiosensitivity profiles.Methods and MaterialsA decision-making model was constructed to maximize the combined recovery of OARs by determining OARs’ optimal rest times. Two main components were incorporated: the cumulative biologically effective dose based on the linear-quadratic model; and a dynamical model capturing the adjusted recovery of OARs as a function of delivered dose. Further, variable radiosensitivity profiles were allowed across the OARs to capture their variable recovery time. Individual recoveries of each OAR under IMRT and the standard TFRT (sTFRT) was compared against optimized TFRT (oTFRT).ResultsFive OARs (larynx, esophagus, parotid, spinal cord, brainstem) were considered. When the cumulative dose delivered under TFRT and IMRT remains the same, three OARs exhibited higher recovery under oTFRT compared to the second-best approach (larynx (81.8% vs. 74.1%), esophagus (95.9% vs. 93.9%), parotid (85.6% vs. 83.5%), while the recovery of spinal cord (90.5% vs. 90.8%) and brainstem (96.2% vs. 96.6%) remained comparable under TFRT and IMRT approaches. With different cumulative dose under TFRT and IMRT, oTFRT achieved significantly higher recovery for larynx (95.5% vs. 81.8%) and parotid (92.9% vs. 85.6%), while it is slightly outperformed by IMRT for esophagus (93.4% vs. 95.9%), spinal cord (87.1% vs. 90.5%), and brainstem (90.2% vs. 96.6%). When considering the minimum end-of-treatment recovery, oTFRT always achieved higher recovery among the other two approaches.ConclusionsBy considering non-identical radiosensitivity profiles of OARs in HNC radiotherapy, TFRT can optimize their rest time to enhance recovery at the end of treatment, potentially reducing patient toxicities.
Global kinetic model of lipid-inducedα-synuclein aggregation and its inhibition by small molecules
Authors: Stevenson Alisdair , Staats Roxine , Dear Alexander J. , Voderholzer David , Meisl Georg , Guido Raphael , Galvagnion Céline , Buell Alexander K. , Knowles Tuomas P.J. , Vendruscolo Michele , Michaels Thomas C.T. 
Published: November 2024

The aggregation ofα-synuclein into amyloid fibrils is a hallmark of Parkinson’s disease. This process has been shown to directly involve interactions between proteins and lipid surfaces when the latter are present. Despite this importance, the molecular mechanisms of lipid-induced amyloid aggregation have remained largely elusive. Here, we present a global kinetic model to describe lipid-induced amyloid aggregation ofα-synuclein. Using this framework we find thatα-synuclein fibrils form via a two-step primary nucleation mechanism and that lipid molecules are directly involved in both the nucleation and fibril elongation steps, giving rise to lipid-protein coaggregates. To illustrate the applicability of this kinetic approach to drug discovery, we identify the mechanism of action of squalamine, a known inhibitor of α-synuclein aggregation, finding that this small molecule reduces the rate of lipid-dependent primary nucleation. Our work will likely guide the rational design ofα-synuclein aggregation inhibitors.Significance StatementAmyloid aggregation is a hallmark of a diverse range of diseases including Parkinson’s Disease, where the proteinα-synuclein is a major con-stituent of proteinaceous deposits found in patients. It is well established that interactions betweenα-synuclein and lipids modulate aggregation. However, the molecular mechanisms driving this lipid-induced aggregation have remained largely elusive, which has frustrated so far the discovery of drugs that prevent lipid-induced aggregation. In this work, we present the first global kinetic model describing lipid-induced aggregation and by integrating this theoretical framework within vitroexperimental data of lipid-inducedα-synuclein aggregation, we reveal the role of lipid membranes in the aggregation process and uncover the mechanism by which small molecule inhibitors interfere with this process.