bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in lipid metabolism track with the progression of neurofibrillary pathology in tauopathies
Authors: Olešová Dominika , Dobešová Dana , Majerová Petra , Brumarová Radana , Kvasnička Aleš , Kouřil Štěpán , Stevens Eva , Hanes Jozef , Fialová Ľubica , Michalicová Alena , Piešťanský Juraj , Šinský Jakub , Kaňovský Petr , Friedecký David , Kováč Andrej 
Published: March 2024

Abstract
Background
Accumulation of tau leads to neuroinflammation and neuronal cell death in tauopathies, including Alzheimer’s disease. As the disease progresses, there is a decline in brain energy metabolism. However, the role of tau protein in regulating lipid metabolism remains less characterized and poorly understood.

Methods
We used a transgenic rat model for tauopathy to reveal metabolic alterations induced by neurofibrillary pathology. Transgenic rats express a tau fragment truncated at the N- and C-terminals. For phenotypic profiling, we performed targeted metabolomic and lipidomic analysis of brain tissue, CSF, and plasma, based on the LC-MS platform. To monitor disease progression, we employed samples from transgenic and control rats aged 4, 6, 8, 10, 12, and 14 months. To study neuron-glia interplay in lipidome changes induced by pathological tau we used well well-established multicomponent cell model system. Univariate and multivariate statistical approaches were used for data evaluation.

Results
We showed that tau has an important role in the deregulation of lipid metabolism. In the lipidomic study, pathological tau was associated with higher production of lipids participating in protein fibrillization, membrane reorganization, and inflammation. Interestingly, significant changes have been found in the early stages of tauopathy before the formation of high-molecular-weight tau aggregates and neurofibrillary pathology. Increased secretion of pathological tau protein in vivo and in vitro induced upregulated production of phospholipids and sphingolipids and accumulation of lipid droplets in microglia. We also found that this process depended on the amount of extracellular tau. During the later stages of tauopathy, we found a connection between the transition of tau into an insoluble fraction and changes in brain metabolism.

Conclusion
Our results revealed that lipid metabolism is significantly affected during different stages of tau pathology. Thus, our results demonstrate that the dysregulation of lipid composition by pathological tau disrupts the microenvironment, further contributing to the propagation of pathology.
Liver-specific adiponectin gene therapy suppresses microglial NLRP3-inflammasome activation for treating Alzheimer’s disease
Authors: Ng Roy Chun-Laam , Jian Min , Ma Oscar Ka-Fai , Xiang Ariya Weiman , Bunting Myriam , Kwan Jason Shing-Cheong , Wong Curtis Wai-Kin , Yick Leung-Wah , Chung Sookja Kim , Lam Karen Siu-Ling , Alexander Ian E. , Xu Aimin , Chan Koon-Ho 
Published: March 2024

AbstractAdiponectin (APN) is an adipokine which predominantly expresses in adipocytes with neuroprotective and anti-inflammatory effects. We have recently indicated that circulatory trimeric APN can enter the brain by crossing the blood–brain barrier (BBB) and modulate microglia-mediated neuroinflammation. Here, we found that the microglial NLR family pyrin domain containing 3 (NLRP3)-inflammasome activation was exacerbated in APN−/−5xFAD mice in age-dependent manner. The focus of this study was to develop a new and tractable therapeutic approach for treating Alzheimer’s disease (AD)-related pathology in 5xFAD mice using peripheral APN gene therapy. We have generated and transduced adeno-associated virus (AAV2/8) expressing the mouse mutated APN gene (APNC39S) into the liver of 5xFAD mice that generated only low-molecular-weight trimeric APN (APNTri). Single dose of AAV2/8-APNC39S in the liver increased circulatory and cerebral APN levels indicating the overexpressed APNTri was able to cross the BBB. Overexpression of APNTri decreased both the soluble and fibrillar Aβ in the brains of 5xFAD mice. AAV2/8-APNTri treatment reduced Aβ-induced IL-1β and IL-18 secretion by suppressing microglial NLRP3-inflammasome activation. The memory functions improved significantly in AAV-APNTri-treated 5xFAD mice with reduction of dystrophic neurites. These findings demonstrate that peripheral gene delivery to overexpress trimeric APN can be a potential therapy for AD.
Graphical Abstract
SARS-CoV-2 outbreak: role of viral proteins and genomic diversity in virus infection and COVID-19 progression
Authors: Hussein Hosni A. M. , Thabet Ali A. , Wardany Ahmed A. , El-Adly Ahmed M. , Ali Mohamed , Hassan Mohamed E. A. , Abdeldayem Mohamed A. B. , Mohamed Abdul-Rahman M. A. , Sobhy Ali , El-Mokhtar Mohamed A. , Afifi Magdy M. , Fathy Samah M. , Sultan Serageldeen 
Published: March 2024

AbstractThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the cause of coronavirus disease 2019 (COVID-19); a severe respiratory distress that has emerged from the city of Wuhan, Hubei province, China during December 2019. COVID-19 is currently the major global health problem and the disease has now spread to most countries in the world. COVID-19 has profoundly impacted human health and activities worldwide. Genetic mutation is one of the essential characteristics of viruses. They do so to adapt to their host or to move to another one. Viral genetic mutations have a high potentiality to impact human health as these mutations grant viruses unique unpredicted characteristics. The difficulty in predicting viral genetic mutations is a significant obstacle in the field. Evidence indicates that SARS-CoV-2 has a variety of genetic mutations and genomic diversity with obvious clinical consequences and implications. In this review, we comprehensively summarized and discussed the currently available knowledge regarding SARS-CoV-2 outbreaks with a fundamental focus on the role of the viral proteins and their mutations in viral infection and COVID-19 progression. We also summarized the clinical implications of SARS-CoV-2 variants and how they affect the disease severity and hinder vaccine development. Finally, we provided a massive phylogenetic analysis of the spike gene of 214 SARS-CoV-2 isolates from different geographical regions all over the world and their associated clinical implications.
Concurrent KRAS p.G12C mutation and ANK3::RET fusion in a patient with metastatic colorectal cancer: a case report
Authors: Bedau Tillmann , Heydt Carina , Siebolts Udo , Zander Thomas , Kraemer Max , Loeser Heike , Buettner Reinhard , Quaas Alexander 
Published: March 2024

Abstract
Background
Colorectal cancer (CRC) frequently involves mutations in the KRAS gene, impacting therapeutic strategies and prognosis. The occurrence of KRAS mutations typically precludes the presence of RET fusions, with current medical literature suggesting a mutual exclusivity between these two genetic alterations. We present a unique case that challenges this notion.

Case Presentation
An 85-year-old female with metastatic CRC was found to have a combination of genetic anomalies that is to the best of our knowledge not yet described in the medical literature: a KRAS p.G12C mutation, associated with oncogenesis and treatment resistance, and an ANK3::RET fusion, an infrequent but targetable mutation in CRC. This molecular profile was uncovered through comprehensive genomic sequencing after the patient experienced metachronous tumor dissemination. The presence of both genetic events complicates the treatment approach.

Conclusions
The identification of both a KRAS p.G12C mutation and an ANK3::RET fusion in the same CRC patient adds a new layer to the oncogenic landscape and treatment considerations for CRC. It highlights the intricate decision-making required in the era of precision medicine, where targeted therapies must be carefully chosen and potentially combined to combat complex genetic profiles. The case emphasizes the urgency of investigating the clinical effects of concurrent or sequential use of KRAS p.G12C and RET inhibitors to inform future therapeutic guidelines and improve patient outcomes in similar cases.
Identification of SARS-CoV-2-specific T cell and its receptor
Authors: Zhang Qian , Liang Qing , Zhang Rui , Wang Nan , Xiao Xu , Shao Jiahao , Wang Kejia 
Published: March 2024

AbstractThe T-cell receptor (TCR) repertoires exhibits distinct signatures associated with COVID-19 severity. However, the precise identification of vaccine-induced SARS-CoV-2-specific TCRs and T-cell immunity mechanisms are unknown. We developed a machine-learning model that can differentiate COVID-19 patients from healthy individuals based on TCR sequence features with an accuracy of 95.7%. Additionally, we identified SARS-CoV-2-specific T cells and TCR in HLA-A*02 vaccinated individuals by peptide stimulation. The SARS-CoV-2-specific T cells exhibited higher cytotoxicity and prolonged survival when targeting spike-pulsed cells in vitro or in vivo. The top-performing TCR was further tested for its affinity and cytotoxic effect against SARS-CoV-2-associated epitopes. Furthermore, single-cell RNA sequencing (scRNA-seq), immune repertoire sequencing (IR-seq) and flow cytometry were used to access vaccine-induced cellular immunity, which demonstrated that robust T cell responses (T cell activation, tissue-resident memory T cell (Trm) generation, and TCR clonal expansion) could be induced by intranasal vaccination. In summary, we identified the SARS-CoV-2-associated TCR repertoires profile, specific TCRs and T cell responses. This study provides a theoretical basis for developing effective immunization strategies.
CDCA5 promoted cell invasion and migration by activating TGF-β1 pathway in human ovarian cancer cells
Authors: Zhang Qingsong , Zhang Rong , Li Yuzhi , Yang Xiaojun 
Published: March 2024

Abstract
Background
The gene cell division cycle associated 5 (CDCA5), also called sororin, has oncogenic characteristics and is upregulated in various carcinomas. Nevertheless, the involvement of CDCA5 in ovarian cancer (OC), a highly aggressive form of cancer, and the underlying mechanism of metastasis remain inadequately investigated.

Results
The bioinformatics data revealed a negative correlation between the patient’s survival and CDCA5 expression, which was overexpressed in OC. Functional assays also confirmed high expression levels of CDCA5 in OC tissues and cells. This suggests that CDCA5 may potentially enhance the motility, migration, and proliferation of OC cells invitro. It impedes DNA damage and apoptosis in OC cells, inhibiting xenograft development in nude mice. The RNA sequencing results suggest CDCA5 is majorly associated with biological functions related to the extracellular matrix (ECM) and influences the transforming growth factor (TGF) signaling pathway. Moreover, subsequent functional investigations elucidated that CDCA5 facilitated the migration and invasion of OC cells viathe TGF-β1/Smad2/3 signaling pathway activation.

Conclusions
CDCA5 may be a strong potential therapeutic target for the treatment and management of OC.
Can artificial intelligence detect type 2 diabetes in women by evaluating the pectoral muscle on tomosynthesis: diagnostic study
Authors: Yashar Meltem M. , Izci Ilayda Begum , Gungoren Fatma Zeynep , Eren Abdulkadir A. , Mert Ali A. , Durur-Subasi Irmak I. 
Published: March 2024

Abstract
Objectives
This retrospective single-center analysis aimed to evaluate whether artificial intelligence can detect type 2 diabetes mellitus by evaluating the pectoral muscle on digital breast tomosynthesis (DBT).

Material method
An analysis of 11,594 DBT images of 287 consecutive female patients (mean age 60, range 40–77 years) was conducted using convolutional neural networks (EfficientNetB5). The inclusion criterion was left-sided screening images with unsuspicious interpretation who also had a current glycosylated hemoglobin A1c (HBA1c) % value. The exclusion criteria were inadequate imaging, history of breast cancer, and/or diabetes mellitus. HbA1c values between 5.6 and 6.4% were categorized as prediabetic, and those with values ≥ 6.5% were categorized as diabetic. A recorded HbA1c ≤ 5.5% served as the control group. Each group was divided into 3 subgroups according to age. Images were subjected to pattern analysis parameters then cropped and resized in a format to contain only pectoral muscle. The dataset was split into 85% for training and 15% for testing the model’s performance. The accuracy rate and F1-score were selected as performance indicators.

Results
The training process was concluded in the 15th epoch, each comprising 1000 steps, with an accuracy rate of 92% and a loss of only 0.22. The average specificity and sensitivity for all 3 groups were 95%. The F1-score was 0.95. AUC-ROC was 0.995. PPV was 94%, and NPV was 98%.

Conclusion
Our study presented a pioneering approach, applying deep learning for the detection of diabetes mellitus status in women using pectoral muscle images and was found to function with an accuracy rate of 92%.

Critical relevance statement
AI can differentiate pathological changes within pectoral muscle tissue by assessing radiological images and maybe a potential diagnostic tool for detecting diabetes mellitus and other diseases that affect muscle tissues.

Key points
• AI may have an opportunistic use as a screening exam for diabetes during digital breast tomosynthesis.
• This technique allows for early and non-invasive detection of diabetes mellitus by AI.
• AI may have broad applications in detecting pathological changes within muscle tissue.

Graphical Abstract
Association of lower extremity peripheral arterial disease with quantitative muscle features from computed tomography angiography
Authors: Hu Ge , Chen Yuexin , Mu Chunlin , Zhang Xinyue , Wang Yun , Wang Yining , Xue Huadan , Zhang Daming , Jin Zhengyu 
Published: March 2024

AbstractObjectivesTo explore the association between lower extremity muscle features from CTA and peripheral arterial disease (PAD) severity using digital subtraction angiography (DSA) as reference standard.MethodsInformed consent was waived for this Institutional Review Board approved retrospective study. PAD patients were recruited from July 2016 to September 2020. Two radiologists evaluated PAD severity on DSA and CTA using runoff score. The patients were divided into two groups: mild PAD (DSA score ≤ 7) vs. severe PAD (DSA score > 7). After segmenting lower extremity muscles from CTA, 95 features were extracted for univariable analysis, logistic regression model (LRM) analysis, and sub-dataset analysis (PAD prediction based on only part of the images). AUC of CTA score and LRMs for PAD prediction were calculated. Features were analyzed using Student’sttest and chi-squared test.p < 0.05 was considered statistically significant.ResultsA total of 56 patients (69 ± 11 years; 38 men) with 56 lower legs were enrolled in this study. The lower leg muscles of mild PAD group (36 patients) showed higher CT values (44.6 vs. 39.5,p < 0.001) with smaller dispersion (35.6 vs. 41.0,p < 0.001) than the severe group (20 patients). The AUC of CTA score, LRM-I (constructed with muscle features), and LRM-II (constructed with muscle features and CTA score) for PAD severity prediction were 0.81, 0.84, and 0.89, respectively. The highest predictive performance was observed in the image subset of the middle and inferior segments of lower extremity (LRM-I, 0.83; LRM-II, 0.90).ConclusionsLower extremity muscle features are associated with PAD severity and can be used for PAD prediction.Critical relevance statementQuantitative image features of lower extremity muscles are associated with the degree of lower leg arterial stenosis/occlusion and can be a beneficial supplement to the current imaging methods of vascular stenosis evaluation for the prediction of peripheral arterial disease severity.Key points• Compared with severe PAD, lower leg muscles of mild PAD showed higher CT values (39.5 vs. 44.6, p < 0.001).• Models developed with muscle CT features had AUC = 0.89 for predicting PAD.• PAD severity prediction can be realized through the middle and inferior segment of images (AUC = 0.90).Graphical Abstract
Repeatability of 18F-FDG uptake in metastatic bone lesions of breast cancer patients and implications for accrual to clinical trials
Authors: Muzi Mark , Peterson Lanell M. , Specht Jennifer M. , Hippe Daniel S. , Novakova-Jiresova Alena , Lee Jean H. , Kurland Brenda F. , Mankoff David A. , Obuchowski Nancy , Linden Hannah M. , Kinahan Paul E. 
Published: March 2024

Abstract
Background
Standard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients that have bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases.

Methods
For this study, nine patients with 38 bone lesions were imaged with 18F-FDG in the same calibrated scanner twice within 14 days. Tumor uptake was quantified by the most commonly used PET parameter, the maximum tumor voxel normalized by dose and body weight (SUVmax) and also by the mean of a 1-cc maximal uptake volume normalized by dose and lean-body-mass (SULpeak). The asymmetric repeatability coefficients with confidence intervals for SUVmax and SULpeak were used to determine the limits of 18F-FDG uptake variability. A second cohort of 28 breast cancer patients with bone-dominant metastases that had 146 metastatic bone lesions was imaged with 18F-FDG before and after standard-of-care therapy for response assessment.

Results
The mean relative difference of SUVmax and SULpeak in 38 bone tumors of the first cohort were 4.3% and 6.7%. The upper and lower asymmetric limits of the repeatability coefficient were 19.4% and − 16.3% for SUVmax, and 21.2% and − 17.5% for SULpeak. 18F-FDG repeatability coefficient confidence intervals resulted in the following patient stratification using SULpeak for the second patient cohort: 11-progressive disease, 5-stable disease, 7-partial response, and 1-complete response with three inevaluable patients. The asymmetric repeatability coefficients response criteria for SULpeak changed the status of 3 patients compared to the standard Positron Emission Tomography Response Criteria in Solid Tumors of ± 30% SULpeak.

Conclusion
In evaluating bone tumor response for breast cancer patients with bone-dominant metastases using 18F-FDG SUVmax, the repeatability coefficients from test-retest studies show that reductions of more than 17% and increases of more than 20% are unlikely to be due to measurement variability. Serial 18F-FDG imaging in clinical trials investigating bone lesions in these patients, such as the ECOG-ACRIN EA1183 trial, benefit from confidence limits that allow interpretation of response.
Improving monitoring and management methods is of the utmost importance in countries at risk of invasion by the pinewood nematode
Authors: Robinet Christelle , Raffin Annie , Jactel Hervé , Kersaudy Emmanuel , Deuffic Philippe , Clopeau Armand , Hotte Hoël , Kleinhentz Marc , Robin Cécile , Roux Géraldine , Villate Laure , Castagnone-Sereno Philippe 
Published: March 2024

Abstract
Key message
The invasive pine wood nematode is a major threat to pine forests worldwide, causing extensive tree mortality. Although scientific knowledge and control measures are continuously improving, important gaps remain. We argue that some key questions, notably related to early detection and pest management, need to be urgently tackled in countries at risk of invasion such as France.
Positive solutions for the Riemann–Liouville-type fractional differential equation system with infinite-point boundary conditions on infinite intervals
Authors: Yu Yang , Ge Qi 
Published: March 2024

AbstractIn this paper, we study the existence and uniqueness of positive solutions for a class of a fractional differential equation system of Riemann–Liouville type on infinite intervals with infinite-point boundary conditions. First, the higher-order equation is reduced to the lower-order equation, and then it is transformed into the equivalent integral equation. Secondly, we obtain the existence and uniqueness of positive solutions for each fixed parameter $\lambda >0$
λ
>
0
by using the mixed monotone operators fixed-point theorem. The results obtained in this paper show that the unique positive solution has good properties: continuity, monotonicity, iteration, and approximation. Finally, an example is given to demonstrate the application of our main results.
Quality assurance of 3D-printed patient specific anatomical models: a systematic review
Authors: Schulze Martin , Juergensen Lukas , Rischen Robert , Toennemann Max , Reischle Gregor , Puetzler Jan , Gosheger Georg , Hasselmann Julian 
Published: March 2024

Abstract
Background
The responsible use of 3D-printing in medicine includes a context-based quality assurance. Considerable literature has been published in this field, yet the quality of assessment varies widely. The limited discriminatory power of some assessment methods challenges the comparison of results. The total error for patient specific anatomical models comprises relevant partial errors of the production process: segmentation error (SegE), digital editing error (DEE), printing error (PrE). The present review provides an overview to improve the general understanding of the process specific errors, quantitative analysis, and standardized terminology.

Methods
This review focuses on literature on quality assurance of patient-specific anatomical models in terms of geometric accuracy published before December 4th, 2022 (n = 139). In an attempt to organize the literature, the publications are assigned to comparable categories and the absolute values of the maximum mean deviation (AMMD) per publication are determined therein.

Results
The three major examined types of original structures are teeth or jaw (n = 52), skull bones without jaw (n = 17) and heart with coronary arteries (n = 16). VPP (vat photopolymerization) is the most frequently employed basic 3D-printing technology (n = 112 experiments). The median values of AMMD (AMMD: The metric AMMD is defined as the largest linear deviation, based on an average value from at least two individual measurements.) are 0.8 mm for the SegE, 0.26 mm for the PrE and 0.825 mm for the total error. No average values are found for the DEE.

Conclusion
The total error is not significantly higher than the partial errors which may compensate each other. Consequently SegE, DEE and PrE should be analyzed individually to describe the result quality as their sum according to rules of error propagation. Current methods for quality assurance of the segmentation are often either realistic and accurate or resource efficient. Future research should focus on implementing models for cost effective evaluations with high accuracy and realism. Our system of categorization may be enhancing the understanding of the overall process and a valuable contribution to the structural design and reporting of future experiments. It can be used to educate specialists for risk assessment and process validation within the additive manufacturing industry.

Graphical Abstract
Context of the figures in this review. Center: Fig. 5+ 7; top (blue): Fig. 8; right (green): Fig. 9; bottom (yellow): Fig. 10; left (red): Fig. 11. A version in high resolution can be found online in the supplementary material.