bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the autonomic nervous system in young, middle-aged, and older individuals with essential hypertension and sleep-related changes in neurocardiac regulation
Authors: Yeh Chia-Hsin , Chen Chun-Yu , Kuo Yu-En , Chen Chieh-Wen , Kuo Terry B. J. , Kuo Kuan-Liang , Chen Hong-Ming , Huang Hsin-Yi , Chern Chang-Ming , Yang Cheryl C. H. 
Published: December 2023

AbstractEssential hypertension involves complex cardiovascular regulation. The autonomic nervous system function fluctuates throughout the sleep–wake cycle and changes with advancing age. However, the precise role of the autonomic nervous system in the development of hypertension during aging remains unclear. In this study, we characterized autonomic function during the sleep–wake cycle in different age groups with essential hypertension. This study included 97 men (53 with and 44 without hypertension) aged 30–79 years. They were stratified by age into young (< 40 years), middle-aged (40–59 years), and older (60–79 years) groups. Polysomnography and blood pressure data were recorded for 2 min before and during an hour-long nap. Autonomic function was assessed by measuring heart rate variability and blood pressure variability. Data were analyzed using t tests, correlation analyses, and two-way analysis of variance. During nonrapid eye movement (nREM), a main effect of age was observed on cardiac parasympathetic measures and baroreflex sensitivity (BRS), with the highest and lowest levels noted in the younger and older groups, respectively. The coefficients of the correlations between these measures and age were lower in patients with hypertension than in normotensive controls. The BRS of young patients with hypertension was similar to that of their middle-aged and older counterparts. However, cardiac sympathetic activity was significantly higher (p = 0.023) and BRS was significantly lower (p = 0.022) in the hypertension group than in the control group. During wakefulness, the results were similar although some of the above findings were absent. Autonomic imbalance, particularly impaired baroreflex, plays a more significant role in younger patients with hypertension. The nREM stage may be suitable for gaining insights into the relevant mechanisms.
Inductive detection of influence operations via graph learning
Authors: Gabriel Nicholas A. , Broniatowski David A. , Johnson Neil F. 
Published: December 2023

AbstractInfluence operations are large-scale efforts to manipulate public opinion. The rapid detection and disruption of these operations is critical for healthy public discourse. Emergent AI technologies may enable novel operations that evade detection and influence public discourse on social media with greater scale, reach, and specificity. New methods of detection with inductive learning capacity will be needed to identify novel operations before they indelibly alter public opinion and events. To this end, we develop an inductive learning framework that: (1) determines content- and graph-based indicators that are not specific to any operation; (2) uses graph learning to encode abstract signatures of coordinated manipulation; and (3) evaluates generalization capacity by training and testing models across operations originating from Russia, China, and Iran. We find that this framework enables strong cross-operation generalization while also revealing salient indicators-illustrating a generic approach which directly complements transductive methodologies, thereby enhancing detection coverage.
Gene expression profiling and protein–protein network analysis revealed prognostic hub biomarkers linking cancer risk in type 2 diabetic patients
Authors: Kasera Harshita , Shekhawat Rajveer Singh , Yadav Pankaj , Singh Priyanka 
Published: December 2023

AbstractType 2 diabetes mellitus (T2DM) and cancer are highly prevalent diseases imposing major health burden globally. Several epidemiological studies indicate increased susceptibility to cancer in T2DM patients. However, genetic factors linking T2DM with cancer have been poorly studied. In this study, we followed computational approaches using the raw gene expression data of peripheral blood mononuclear cells of T2DM and cancer patients available in the gene expression omnibus (GEO) database. Our analysis identified shared differentially expressed genes (DEGs) in T2DM and three common cancer types, namely, pancreatic cancer (PC), liver cancer (LC), and breast cancer (BC). The functional and pathway enrichment analysis of identified common DEGs highlighted the involvement of critical biological pathways, including cell cycle events, immune system processes, cell morphogenesis, gene expression, and metabolism. We retrieved the protein–protein interaction network for the top DEGs to deduce molecular-level interactions. The network analysis found 7, 6, and 5 common hub genes in T2DM vs. PC, T2DM vs. LC, and T2DM vs. BC comparisons, respectively. Overall, our analysis identified important genetic markers potentially able to predict the chances of PC, LC, and BC onset in T2DM patients.
Investigation of perfusion impairment in degenerative cervical myelopathy beyond the site of cord compression
Authors: Lebret Anna , Lévy Simon , Pfender Nikolai , Farshad Mazda , Altorfer Franziska C. S. , Callot Virginie , Curt Armin , Freund Patrick , Seif Maryam 
Published: December 2023

AbstractThe aim of this study was to determine tissue-specific blood perfusion impairment of the cervical cord above the compression site in patients with degenerative cervical myelopathy (DCM) using intravoxel incoherent motion (IVIM) imaging. A quantitative MRI protocol, including structural and IVIM imaging, was conducted in healthy controls and patients. In patients, T2-weighted scans were acquired to quantify intramedullary signal changes, the maximal canal compromise, and the maximal cord compression. T2*-weighted MRI and IVIM were applied in all participants in the cervical cord (covering C1–C3 levels) to determine white matter (WM) and grey matter (GM) cross-sectional areas (as a marker of atrophy), and tissue-specific perfusion indices, respectively. IVIM imaging resulted in microvascular volume fraction ($$F$$
F
), blood velocity ($$D^{*}$$

D

∗

), and blood flow ($$F \cdot D^{*}$$

F
·

D

∗

) indices. DCM patients additionally underwent a standard neurological clinical assessment. Regression analysis assessed associations between perfusion parameters, clinical outcome measures, and remote spinal cord atrophy. Twenty-nine DCM patients and 30 healthy controls were enrolled in the study. At the level of stenosis, 11 patients showed focal radiological evidence of cervical myelopathy. Above the stenosis level, cord atrophy was observed in the WM (− 9.3%; p = 0.005) and GM (− 6.3%; p = 0.008) in patients compared to healthy controls. Blood velocity (BV) and blood flow (BF) indices were decreased in the ventral horns of the GM (BV: − 20.1%, p = 0.0009; BF: − 28.2%, p = 0.0008), in the ventral funiculi (BV: − 18.2%, p = 0.01; BF: − 21.5%, p = 0.04) and lateral funiculi (BV: − 8.5%, p = 0.03; BF: − 16.5%, p = 0.03) of the WM, across C1–C3 levels. A decrease in microvascular volume fraction was associated with GM atrophy (R = 0.46, p = 0.02). This study demonstrates tissue-specific cervical perfusion impairment rostral to the compression site in DCM patients. IVIM indices are sensitive to remote perfusion changes in the cervical cord in DCM and may serve as neuroimaging biomarkers of hemodynamic impairment in future studies. The association between perfusion impairment and cervical cord atrophy indicates that changes in hemodynamics caused by compression may contribute to the neurodegenerative processes in DCM.
Construction and validation of a novel lysosomal signature for hepatocellular carcinoma prognosis, diagnosis, and therapeutic decision-making
Authors: Chen Jianlin , Gao Gan , He Yufang , Zhang Yi , Wu Haixia , Dai Peng , Zheng Qingzhu , Huang Hengbin , Weng Jiamiao , Zheng Yue , Huang Yi 
Published: December 2023

AbstractLysosomes is a well-recognized oncogenic driver and chemoresistance across variable cancer types, and has been associated with tumor invasiveness, metastasis, and poor prognosis. However, the significance of lysosomes in hepatocellular carcinoma (HCC) is not well understood. Lysosomes-related genes (LRGs) were downloaded from Genome Enrichment Analysis (GSEA) databases. Lysosome-related risk score (LRRS), including eight LRGs, was constructed via expression difference analysis (DEGs), univariate and LASSO-penalized Cox regression algorithm based on the TCGA cohort, while the ICGC cohort was obtained for signature validation. Based on GSE149614 Single-cell RNA sequencing data, model gene expression and liver tumor niche were further analyzed. Moreover, the functional enrichments, tumor microenvironment (TME), and genomic variation landscape between LRRSlow/LRRShigh subgroup were systematically investigated. A total of 15 Lysosomes-related differentially expressed genes (DELRGs) in HCC were detected, and then 10 prognosis DELRGs were screened out. Finally, the 8 optimal DELRGs (CLN3, GBA, CTSA, BSG, APLN, SORT1, ANXA2, and LAPTM4B) were selected to construct the LRRS prognosis signature of HCC. LRRS was considered as an independent prognostic factor and was associated with advanced clinicopathological features. LRRS also proved to be a potential marker for HCC diagnosis, especially for early-stage HCC. Then, a nomogram integrating the LRRS and clinical parameters was set up displaying great prognostic predictive performance. Moreover, patients with high LRRS showed higher tumor stemness, higher heterogeneity, and higher genomic alteration status than those in the low LRRS group and enriched in metabolism-related pathways, suggesting its underlying role in the progression and development of liver cancer. Meanwhile, the LRRS can affect the proportion of immunosuppressive cell infiltration, making it a vital immunosuppressive factor in the tumor microenvironment. Additionally, HCC patients with low LRRS were more sensitive to immunotherapy, while patients in the high LRRS group responded better to chemotherapy. Upon single-cell RNA sequencing, CLN3, GBA, and LAPTM4B were found to be specially expressed in hepatocytes, where they promoted cell progression. Finally, RT-qPCR and external datasets confirmed the mRNA expression levels of model genes. This study provided a direct links between LRRS signature and clinical characteristics, tumor microenvironment, and clinical drug-response, highlighting the critical role of lysosome in the development and treatment resistance of liver cancer, providing valuable insights into the prognosis prediction and treatment response of HCC, thereby providing valuable insights into prognostic prediction, early diagnosis, and therapeutic response of HCC.
Validation of cost-efficient EEG experimental setup for neural tracking in an auditory attention task
Authors: Ha Jiyeon , Baek Seung-Cheol , Lim Yoonseob , Chung Jae Ho 
Published: December 2023

AbstractWhen individuals listen to speech, their neural activity phase-locks to the slow temporal rhythm, which is commonly referred to as “neural tracking”. The neural tracking mechanism allows for the detection of an attended sound source in a multi-talker situation by decoding neural signals obtained by electroencephalography (EEG), known as auditory attention decoding (AAD). Neural tracking with AAD can be utilized as an objective measurement tool for diverse clinical contexts, and it has potential to be applied to neuro-steered hearing devices. To effectively utilize this technology, it is essential to enhance the accessibility of EEG experimental setup and analysis. The aim of the study was to develop a cost-efficient neural tracking system and validate the feasibility of neural tracking measurement by conducting an AAD task using an offline and real-time decoder model outside the soundproof environment. We devised a neural tracking system capable of conducting AAD experiments using an OpenBCI and Arduino board. Nine participants were recruited to assess the performance of the AAD using the developed system, which involved presenting competing speech signals in an experiment setting without soundproofing. As a result, the offline decoder model demonstrated an average performance of 90%, and real-time decoder model exhibited a performance of 78%. The present study demonstrates the feasibility of implementing neural tracking and AAD using cost-effective devices in a practical environment.
Incidence of bacterial and fungal infections in Polish pediatric patients with acute lymphoblastic leukemia during the pandemic
Authors: Zawitkowska Joanna , Drabko Katarzyna , Lejman Monika , Kowalczyk Adrian , Czyżewski Krzysztof , Dziedzic Magdalena , Jaremek Kamila , Zalas-Więcek Patrycja , Szmydki-Baran Anna , Hutnik Łukasz , Czogała Wojciech , Balwierz Walentyna , Żak Iwona , Salamonowicz-Bodzioch Małgorzata , Kazanowska Bernarda , Wróbel Grażyna , Frączkiewicz Jowita , Kałwak Krzysztof , Tomaszewska Renata , Szczepański Tomasz , Zając-Spychała Olga , Wachowiak Jacek , Płonowski Marcin , Krawczuk-Rybak Maryna , Królak Aleksandra , Ociepa Tomasz , Urasiński Tomasz , Pierlejewski Filip , Młynarski Wojciech , Urbańska-Rakus Justyna , Machnik Katarzyna , Pająk Sonia , Badowska Wanda , Brzeski Tomasz , Mycko Katarzyna , Mańko-Glińska Hanna , Urbanek-Dądela Agnieszka , Karolczyk Grażyna , Mizia-Malarz Agnieszka , Stolpa Weronika , Skowron-Kandzia Katarzyna , Musiał Jakub , Chaber Radosław , Irga-Jaworska Ninela , Bień Ewa , Styczyński Jan 
Published: December 2023

AbstractThe most common complications related to the treatment of childhood acute lymphoblastic leukemia (ALL) are infections. The aim of the study was to analyze the incidence and mortality rates among pediatric patients with ALL who were treated in 17 Polish pediatric hematology centers in 2020–2021 during the pandemic. Additionally, we compared these results with those of our previous study, which we conducted in the years 2012–2017. The retrospective analysis included 460 patients aged 1–18 years with newly diagnosed ALL. In our study, 361/460 (78.5%) children were reported to have microbiologically documented bacterial infections during chemotherapy. Ten patients (2.8%) died due to sepsis. Fungal infections were reported in 99 children (21.5%), of whom five (5.1%) died due to the infection. We especially observed an increase in bacterial infections during the pandemic period compared to the previous study. The directions of our actions should be to consider antibiotic prophylaxis, shorten the duration of hospitalization, and educate parents and medical staff about complications (mainly infections) during anticancer therapy. It is necessary to continue clinical studies evaluating infection prophylaxis to improve outcomes in childhood ALL patients.
Diabetic choriocapillaris flow deficits affect the outer retina and are related to hemoglobin A1c and systolic blood pressure levels
Authors: Nagai Norihiro , Mushiga Yasuaki , Ozawa Yoko 
Published: December 2023

AbstractPatient systemic and ocular data based on optical coherence tomography (OCT) and OCT angiography images were analyzed (n = 45; control and diabetic eyes with or without diabetic retinopathy [DR]; mean age, 49.6 ± 8.1 years). All participants had best-corrected visual acuity < 0.05 in logMAR. The choriocapillaris flow area (CCFA) ratio was lower and the coefficient of variation (CV) of CCFA ratio was higher in diabetic eyes with or without DR than in control eyes. CCFA ratio of DR eyes was lower than that of diabetic eyes without DR. Superficial retinal vessel length density (VLD) was reduced only in DR eyes. CCFA ratio correlated with retinal VLD, photoreceptor outer segment (PROS) length, and retinal pigment epithelium (RPE) volume in the study population; mean PROS decreased in diabetic eyes with or without DR, and RPE volume increased in DR eyes. CCFA ratio < 65.9% and CV of CCFA ratio ≥ 0.140 were more frequently found in diabetic eyes (odds ratio [OR], 13.333; P = 0.001), and related to HbA1c ≥ 7.0% (OR, 4.992; 95% confidence interval [CI] 1.164–21.412; P = 0.030) or systolic blood pressure ≥ 135 mmHg (OR, 5.572; 95% CI 1.156–26.863; P = 0.032). These findings could help understand diabetic pathogenesis in the choriocapillaris and outer retina, and remind clinicians to manage both diabetes and hypertension.
Retina image segmentation using the three-path Unet model
Authors: Liu Ruihua , Pu Wei , Nan Haoyu , Zou Yangyang 
Published: December 2023

AbstractUnsupervised image segmentation is a technique that divides an image into distinct regions or objects without prior labeling. This approach offers flexibility and adaptability to various types of image data. Particularly for large datasets, it eliminates the need for manual labeling, thereby it presents advantages in terms of time and labor costs. However, when applied to retinal image segmentation, challenges arise due to variations in data, presence of noise, and manual threshold adjustments, which can lead to over-segmentation or under-segmentation of small blood vessel boundaries and endpoints. In order to enhance the precision and accuracy of retinal image segmentation, we propose a novel image supervised segmentation network based on three-path Unet model.Firstly, the Haar wavelet transform is employed to extract high-frequency image information, which forms the foundation for the proposed HaarNet, a Unet-inspired architecture. Next, the HaarNet is integrated with the Unet and SegNet frameworks to develop a three-path Unet model, referred to as TP-Unet. Finally, the model is further refined into TP-Unet+AE+DSL by incorporating the advantages of auto-encoding (AE) and deep supervised learning (DSL) techniques, thereby enhancing the overall performance of the system. To evaluate the effectiveness of our proposed model, we conduct experiments using the DRIVE and CHASE public datasets. On the DRIVE dataset, our recommended model achieves a Dice coefficient of 0.8291 and a sensitivity index of 0.8184. These results significantly outperform the Unet model by $$1.34\%$$

1.34
%

and $$2.60\%$$

2.60
%

, respectively. Furthermore, our model demonstrates excellent performance on the CHASE dataset, with a Dice coefficient of 0.8162, a sensitivity of 0.8242, and an accuracy of 0.9664. These metrics surpass the Unet model by $$3.20\%$$

3.20
%

, $$6.66\%$$

6.66
%

, and $$0.42\%$$

0.42
%

, respectively. Our proposed model provides more accurate and reliable results for retinal vessel segmentation, which holds significant potential for assisting doctors in their diagnosis.
Targeted inhibition of the ATR/CHK1 pathway overcomes resistance to olaparib and dysregulates DNA damage response protein expression in BRCA2MUT ovarian cancer cells
Authors: Biegała Łukasz , Gajek Arkadiusz , Szymczak-Pajor Izabela , Marczak Agnieszka , Śliwińska Agnieszka , Rogalska Aneta 
Published: December 2023

AbstractOlaparib is a PARP inhibitor (PARPi) approved for targeted treatment of ovarian cancer (OC). However, its efficacy is impeded by the inevitable occurrence of resistance. Here, we investigated whether the cytotoxic activity of olaparib could be synergistically enhanced in olaparib-resistant OC cells with BRCA2 reversion mutation by the addition of inhibitors of the ATR/CHK1 pathway. Moreover, we provide insights into alterations in the DNA damage response (DDR) pathway induced by combination treatments. Antitumor activity of olaparib alone or combined with an ATR inhibitor (ATRi, ceralasertib) or CHK1 inhibitor (CHK1i, MK-8776) was evaluated in OC cell lines sensitive (PEO1, PEO4) and resistant (PEO1-OR) to olaparib. Antibody microarrays were used to explore changes in expression of 27 DDR-related proteins. Olaparib in combination with ATR/CHK1 inhibitors synergistically induced a decrease in viability and clonogenic survival and an increase in apoptosis mediated by caspase-3/7 in all OC cells. Combination treatments induced cumulative alterations in expression of DDR-related proteins mediating distinct DNA repair pathways and cell cycle control. In the presence of ATRi and CHK1i, olaparib-induced upregulation of proteins determining cell fate after DNA damage (PARP1, CHK1, c-Abl, Ku70, Ku80, MDM2, and p21) was abrogated in PEO1-OR cells. Overall, the addition of ATRi or CHK1i to olaparib effectively overcomes resistance to PARPi exerting anti-proliferative effect in BRCA2MUT olaparib-resistant OC cells and alters expression of DDR-related proteins. These new molecular insights into cellular response to olaparib combined with ATR/CHK1 inhibitors might help improve targeted therapies for olaparib-resistant OC.
Treatment cessation in HBeAg-negative chronic hepatitis B: clinical response is associated with increase in specific proinflammatory cytokines
Authors: Holmberg Marte , Aass Hans Christian D. , Dalgard Olav , Samuelsen Ellen , Sun Dan , Björkström Niklas K. , Johannessen Asgeir , Reikvam Dag Henrik 
Published: December 2023

AbstractPatients with HBeAg-negative chronic hepatitis B may experience an immune response after stopping nucleos(t)ide analogue (NA)therapy, which may potentially trigger HBsAg loss or off-therapy sustained viral control. The immunological mechanisms determining clinical response remain poorly understood. To identify inflammatory signatures associated with defined outcomes, we analysed plasma cytokines and chemokines from 57 HBeAg-negative patients enrolled in the Nuc-Stop Study at baseline and 12 weeks after NA cessation. Clinical response at 12 weeks was classified into four groups: immune control, viral relapse, evolving clinical relapse, and resolving clinical relapse. Twelve weeks after treatment cessation 17 patients (30%) experienced immune control, 19 (33%) viral relapse, 6 (11%) evolving clinical relapse, and 15 (26%) resolving clinical relapse. There was a significant increase in interferon-γ-induced protein 10 (IP-10; p = 0.012) and tumor necrosis factor (TNF; p = 0.032) in patients with evolving clinical relapse. Sparse partial least-squares multivariate analyses (sPLS-DA) showed higher first component values for the clinical relapse group compared to the other groups, separation was driven mainly by IP-10, TNF, IL-9, IFN-γ, MIP-1β, and IL-12. Our results demonstrate that evolving clinical relapse after NA cessation is associated with a systemic increase in the proinflammatory cytokines IP-10 and TNF.Clinical trial registration: ClinicalTrials.gov, Identifier: NCT03681132.
Modulation of memory reconsolidation by adjacent novel tasks: timing defines the nature of change
Authors: Schroeder Matías Nicolás , Fullio Camila L. , Ballarini Fabricio , Moncada Diego 
Published: December 2023

AbstractReconsolidation turns memories into a responsive state that allows their modulation until they stabilize again. This phenomenon attracted remarkable attention due to its potential impact on therapeutics and education. Recent evidence revealed that different memories undergo reconsolidation via a behavioral tagging process. Thus, their re-stabilization involves setting “reconsolidation-tags” and synthesizing plasticity-related proteins for their capture at the tagged sites. Here, we studied the possibility of affecting these fundamental mechanisms to modulate reconsolidation. Our findings, in laboratory rats, indicate that exploring a novel environment 60 min before or after memory reactivation improves spatial object recognition memory by promoting protein synthesis. Conversely, experiencing novelty immediately after reactivation impairs the reconsolidation by affecting the tags. Similar effects, but with a different optimal time window for improvement, occur in inhibitory avoidance memory. These results highlight the possibility of modulating existing memories using non-invasive interventions that selectively affect the fundamental mechanisms of behavioral tagging during their reconsolidation.