bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adherence to oral antiretroviral therapy in Canada, 2010–2020: A retrospective analysis of claims data
Authors: Angel Jonathan B. , Freilich Jonatan , Arthurs Erin , Ban Joann K. , Lachaine Jean , Chounta Vasiliki , Harris Marianne 
Published: July 2023

Objective:
To assess antiretroviral therapy (ART) adherence among people living with HIV (PLHIV) in Canada and identify baseline characteristics associated with suboptimal adherence (<95%).

Design:
Retrospective observational study using data from the National Prescription Drug Utilization Information System and Régie de l’assurance maladie Quebec (RAMQ) Public Prescription Drug Insurance Plan.

Methods:
This analysis included PLHIV aged 18 years or older who initiated an ART regimen and were followed for at least 12 months (2010–2020). Patient characteristics were summarized using medical/pharmacy claims data from seven provinces (Alberta, Manitoba, New Brunswick, Newfoundland and Labrador, Ontario, Saskatchewan, and Quebec). ART regimen at index date (first dispensing of a regimen including a core agent) was defined as a single- or multi-tablet regimen. Adherence was calculated using a Proportion of Days Covered approach, based on ART dispensing, recorded between April 2010 and the last available date. Multivariate linear regression analysis was used to determine correlations between suboptimal adherence and baseline characteristics.

Results:
We identified 19,322 eligible PLHIV, 44.7% of whom had suboptimal adherence (<95%). Among 12,594 PLHIV with evaluable baseline data, 10,673 (84.8%) were ART naïve, 74.2% were male, mean age was 42.9 years, and 54.1% received a multi-tablet regimen as their ART. Based on multivariate regression analysis, suboptimal adherence was significantly associated with multi-tablet ART (p < 0.001) and younger age (p < 0.001), but not sex.

Conclusion:
Almost half of adult PLHIV in Canada had suboptimal adherence to ART. Better understanding of factors influencing adherence may help address gaps in current care practices that may impact adherence.
Computed Tomography–Based Deep Learning Model for Assessing the Severity of Patients With Connective Tissue Disease–Associated Interstitial Lung Disease
Authors: Su Ningling , Hou Fan , Zheng Wen , Wu Zhifeng , E Linning 
Published: July 2023

Objectives
This study aimed to develop a computed tomography (CT)–based deep learning model for assessing the severity of patients with connective tissue disease (CTD)–associated interstitial lung disease (ILD).

Methods
The retrospective study included 298 CTD-ILD patients between January 2018 and May 2022. A deep learning–based RDNet model was established (1610 fully annotated CT images for training and 402 images for validation). The model was used to automatically classify and quantify 3 radiologic features (ground glass opacities [GGOs], reticulation, and honeycombing), along with a volumetric sum of 3 areas (ILD%). As a control, we used 4 previously defined CT threshold methods to calculate the ILD assessment index. The Spearman rank correlation coefficient (r) evaluated the correlation between various indicators and the lung function index in the remaining 184 CTD-ILD patients who were staged according to the gender-age-physiology (GAP) system.

Results
The RDNet model accurately identified GGOs, reticulation, and honeycombing, with corresponding Dice indexes of 0.784, 0.782, and 0.747, respectively. A total of 137 patients were at GAP1 (73.9%), 36 patients at GAP2 (19.6%), and 11 patients at GAP3 (6.0%). The percentages of reticulation and honeycombing at GAP2 and GAP3 were markedly elevated compared with those at GAP1 (P < 0.001). The percentage of GGOs was not significantly different among the GAP stages (P = 0.62). As the GAP stage increased, all lung function indicators tended to decrease, and the composite physiologic index (CPI) indicated an upward tendency. The percentage of honeycombs moderately correlated with the percentage of diffusing capacity of the lung for carbon monoxide (DLco%) (r = −0.58, P < 0.001) and CPI (r = 0.63, P < 0.001). The ILD assessment index calculated by the CT threshold method (−260 to −600 Hounsfield units) had a low correlation with DLco% and CPI (DLco%: r = −0.42, P < 0.001; CPI: r = 0.45, P < 0.001).

Conclusions
The RDNet model can quantify GGOs, reticulation, and honeycombing of chest CT images in CTD-ILD patients, among which honeycombing had the most significant effect on lung function indicators. In addition, this model provided good clinical utility for evaluating the severity of CTD-ILD.
C-Arm Computed Tomographic Image Fusion for Repetitive Transarterial Chemoembolization of Hepatocellular Carcinoma
Authors: Choi Yelim , Jeong Yun Soo , Hwang Jang Soon , Kim Hyo-Cheol , Chung Jin Wook , Choi Jin Woo 
Published: July 2023

Objective
The aim of this study was to evaluate the potential implications of fusion imaging with C-arm computed tomography (CACT) scans for repetitive conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma.

Materials and Methods
Fifty-six cTACE sessions were performed using fusion CACT images from September 2020 to June 2021 in a tertiary referral center, and the data were retrospectively analyzed. Fusion of unenhanced and enhanced CACT images was considered when previously accumulated iodized oil hampered the identification of local tumor progression or intrahepatic distant metastasis (indication A), when a tumor was supplied by multiple arteries with different origins from the aorta and missing tumor enhancement was suspected (indication B), or when iodized oil distribution on immediate post-cTACE CACT images needed to be precisely compared with the pre-cTACE images (indication C). Fusion image quality, initial tumor response, time to local progression (TTLP) of index tumors, and time to progression (TTP) were evaluated.

Results
The fusion quality was satisfactory with a mean misregistration distance of 1.4 mm. For the 40 patients with indication A, the initial tumor responses at 3 months were nonviable, equivocal, and viable in 27 (67.5%), 4 (10.0%), and 9 (22.5%) index tumors, respectively. The median TTLP and TTP were 14.8 months and 4.5 months, respectively. For 10 patients with indication B, the median TTLP and TTP were 8.3 months and 2.6 months, respectively. Among the 6 patients with indication C, 2 patients were additionally treated at the same cTACE session after confirming incomplete iodized oil uptake on fusion imaging.

Conclusions
Fusion CACT images are useful in patients with hepatocellular carcinoma undergoing repetitive cTACE.
Does Adjuvant Gamma Knife Stereotactic Radiosurgery Have a Role in Treating Optic Nerve Sheath Meningiomas?
Authors: Wei Zhishuo , Taori Suchet , Song Shanshan , Deng Hansen , Niranjan Ajay , Lunsford L. Dade 
Published: July 2023

Background:
Meningiomas arising from or adjacent to the optic nerve sheath meningioma (ONSM) are management challenges because of their risk of visual loss. Stereotactic radiosurgery (SRS) is a minimally invasive modality that can be added as adjuvant treatment for patients whose tumor has progressed or recurred after initial resection.

Methods:
The authors retrospectively reviewed 2,030 meningioma patients who underwent SRS between 1987 and 2022. In total, 7 patients (4 females; median age = 49) were found with tumors originating from the optic nerve sheath. None of the patients had tumors that engulfed the optic nerve as such tumors typically undergo fractionated radiation therapy (FRT) to preserve vision. The clinical history, visual function, and radiographic and neurological findings were characterized. Outcome measures included visual status, tumor control, and the need for additional management.

Results:
All patients underwent either initial gross total (n = 1) or partial surgical resection (n = 6) before SRS. Two patients with progressive tumor growth also had SRS after failing additional fractionated radiation after surgery (54 Gy, 30 fractions for both patients). The median time between the date of surgery and the SRS procedure date was 38 months. The Leksell Gamma Knife was used to deliver a margin dose of 12 Gy (range: 8–14 Gy) to a median cumulative tumor volume of 3.3 cc (range: 1.2–18 cc). The median maximal optic nerve radiation dose was 6.5 Gy (range: 1.9–8.1 Gy). After SRS, the median follow-up time was 130 months (range: 26–169 months). Two patients showed local tumor progression at 20 and 55 months after SRS. Four had stable visual function, 2 experienced improved visual acuity, and 1 patient had visual deterioration.

Conclusions:
Meningiomas arising from (but not engulfing the optic nerve) represent management quandaries after failed initial surgical removal. In this experience, salvage SRS was associated with tumor control and vision preservation in 5 of 7 patients. Additional experience with this strategy may further define the role of SRS both as a salvage and primary option.
Hypoxic Microenvironment Promotes PTBP1 Lactonization and IGF2BP2 Read Defects Mediate the Development of Preeclampsia
Authors: Qu Hongmei , Li Xiaoyan , Li Qian , Yang Xiaoming , Feng Yan , Yu Li , Qu Liping , Mu Linsong , Zou Yanfen , Chu Yongli 
Published: July 2023

AbstractObjectiveAs an idiopathic hypertensive disorder of pregnancy, pre-eclampsia (PE) remains a major cause of maternal and neonatal morbidity and mortality, with no effective strategy for causal treatment.MethodsThis study was performed by downloading the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/) based on the GSE173193 dataset, including single-cell sequencing data from placental samples of two PE patients and two normal controls. Placental cell subpopulations and their transcriptional heterogeneity were compared between PE and healthy pregnancies, and the mechanisms of PE cell dynamics in the hypoxic microenvironment were confirmed by in vitro experiments.ResultsIn this study, we constructed a large-scale single-cell transcriptome ecological landscape of 26,416 cells from healthy pregnant and PE patients placenta and further identified a PE-specific CSNK2B-positive subpopulation of chorionic villous trophoblast (EVT) cells. Specifically, this study revealed that the EVT subpopulation PTBP1 was inactivated by lactonization in the hypoxic microenvironment, resulting in low expression of the N6-methyladenosine (m6A) reading protein IGF2BP2. On the basis of this, low expression of IGF2BP2 inhibits mitochondrial autophagy, causes the accumulation of damaged mitochondria, exacerbates lactic acid accumulation while inducing EVT apoptosis on the one hand. In particular, hypoxia may initially promote oxidative stress through the production of mitochondrial reactive oxygen species. on the other hand, it inhibits EVT adherent spot signaling, decreases EVT invasive ability, leads to impaired placental spiral vessel recast, and promotes PE disease process. In addition, there are interactions between abnormal metabolic signaling of PE-specific EVT subpopulations and microenvironmental immune cells, which activate metabolic inflammation.ConclusionThe present study not only provides a new cell biological and genetic basis for elucidating the pathogenesis of PE, but also contributes to the design of an allopathic treatment strategy for PE.
Exploring Genetic Associations of Three Types of Risk Factors with Ischemic Stroke: An Integrated Bioinformatics Study
Authors: Liu Yi , Wang Weili , Cui Xin , Xie Yanming 
Published: July 2023

AbstractBackgroundIschemic stroke (IS) is a primary cause of disability and mortality globally. More and more reports suggest a strong association between blood pressure, blood glucose, and blood lipids and their metabolic products with IS.MethodsWe extracted the genetic tools of blood pressure, blood glucose, and blood lipids and their metabolites as instrumental variables, which were then paired with GWAS data on IS and a Mendelian randomization (MR) analysis was performed to assess the effect of these exposures on the disease. Following the positive results, colocalization analysis was performed to identify shared genes associated with exposures and IS. We then performed differential expression analysis using the GEO dataset to identify the differentially expressed associated genes (DEAGs) from associated shared genes. Additional analyzes were performed on these DEAGs to obtain their importance scores using four machine learning models. A nomogram was created using genes with high importance scores to predict the level of risk assessment between DEAGs and IS.ResultsThere is a positive correlation between blood pressure, blood glucose and the risk of IS onset, while blood lipids and their metabolic products are positively or negatively correlated with the risk. There are 64 shared genes of blood pressure, blood lipids and their metabolic products with IS. Thirteen DEAGs were obtained, and among which FURIN, MAN2A2, HDDC3, ALDH2, and TOMM40 were identified as feature genes for creating the nomogram which can quantitatively predict the risk of IS onset with the expression of these feature genes. By cluster analysis, we found that DEAGs expression underlying immune inflammation, angiogenesis and development, lipid metabolism, etc.ConclusionThis study suggests a significant association between blood pressure, blood glucose, and blood lipids and their metabolic products with IS, and predicts that these exposures mainly regulate the occurrence, development, and prognosis of IS through mechanisms such as DNA repair, DNA methylation, mitochondrial repair, apoptosis, autophagy, etc.
Learning Complete Protein Representation by Deep Coupling of Sequence and Structure
Authors: Hu Bozhen , Tan Cheng , Xia Jun , Zheng Jiangbin , Huang Yufei , Wu Lirong , Liu Yue , Xu Yongjie , Li Stan Z. 
Published: July 2023

AbstractLearning effective representations is crucial for understanding proteins and their biological functions. Recent advancements in language models and graph neural networks have enabled protein models to leverage primary or tertiary structure information to learn representations. However, the lack of practical methods to deeply co-model the relationships between protein sequences and structures has led to suboptimal embeddings. In this work, we propose CoupleNet, a network that couples protein sequence and structure to obtain informative protein representations. CoupleNet incorporates multiple levels of features in proteins, including the residue identities and positions for sequences, as well as geometric representations for tertiary structures. We construct two types of graphs to model the extracted sequential features and structural geometries, achieving completeness on these graphs, respectively, and perform convolution on nodes and edges simultaneously to obtain superior embeddings. Experimental results on a range of tasks, such as protein fold classification and function prediction, demonstrate that our proposed model outperforms the state-of-the-art methods by large margins.
Outcome devaluation by sensory-specific satiety alters Pavlovian-conditioned behavior in male and female rats
Authors: Sood Ankit , Richard Jocelyn M. 
Published: July 2023

AbstractGoal-directed behavior relies on accurate mental representations of the value of expected outcomes. Disruptions to this process are a central feature of several neuropsychiatric disorders, including addiction. Goal-directed behavior is most frequently studied using instrumental paradigms paired with outcome devaluation, but cue-evoked behaviors in Pavlovian settings can also be goal-directed and therefore sensitive to changes in outcome value. Emerging literature suggests that male and female rats may differ in the degree to which their Pavlovian-conditioned responses are goal-directed, but interpretation of these findings is complicated by the tendency of female and male rats to engage in distinct types of Pavlovian responses when trained with localizable cues. Here, we used outcome devaluation via sensory-specific satiety to assess the behavioral responses in male and female Long Evans rats trained to respond to an auditory CS (conditioned stimulus) in a Pavlovian-conditioning paradigm. We found that satiety-induced devaluation led to a decrease in behavioral responding to the reward-predictive CS, with males showing an effect on both port entry latency and probability and females showing an effect only on port entry probability. Overall, our results suggest that outcome devaluation affects Pavlovian-conditioned responses in both male and female rats, but that females may be less sensitive to outcome devaluation.
KISS1 is a potential immunological and prognostic biomarker for cancer metastasis in pan-cancer and affects breast cancer in a different way
Authors: Jiang Hao , Xiao Jianru , Zhang Hao , Li Bo , Xu Wei , Li Zhenxi 
Published: July 2023

ABSTRACTMetastasis to other organs accounts for the majority of death in cancer patients. Metastatic capacity enables tumor cells resist to chemotherapy. KISS1 had been found to suppress metastasis in cancers like melanoma, but improve the metastatic phenotype of breast cancers, which means its role in tumor metastasis is tissue context-dependent. This character suggests the KISS1 might have promising potential to interpret tumor metastasis in a pan-cancer perspective. Here, we analyzed the potential functions of KISS1 in pan-cancer, especially in breast cancer, by the datasets of TCGA and GTEx. KISS1 exhibited a different expression status between mRNA level and protein level in pan-cancers, with a significant association between KISS1 expression and prognosis of cancer patients. Besides, the correlation between KISS1 expression and immune cell infiltration, immunosuppressive cells, immune checkpoint genes, TMB, MSI, tumor purity and HRD indicates the potential role in regulating immunotherapy. Thereafter, we further clarified the role of KISS1 in promoting metastasis in breast cancer. Furthermore, we found that the post-translational modification may explains the KISS1 protein stability in breast cancers. In summary, our first pan-cancer study offers new insights and relatively comprehensive understandings of the oncogenic roles of KISS1 across various cancers.
Mitonuclear sex determination? Empirical evidence from bivalves
Authors: Smith Chase H. , Mejia-Trujillo Raquel , Breton Sophie , Pinto Brendan J. , Kirkpatrick Mark , Havird Justin C. 
Published: July 2023

AbstractGenetic elements encoded in nuclear DNA determine the sex of an individual in many animals. In bivalves, however, mitochondrial DNA (mtDNA) has been hypothesized to contribute to sex determination in lineages that possess doubly uniparental inheritance (DUI). In these cases, females transmit a female mtDNA (F mtDNA) to all offspring, while male mtDNA (M mtDNA) is transmitted only from fathers to sons. Because M mtDNA is inherited in the same way as Y chromosomes, it has been hypothesized that mtDNA may be responsible for sex determination. However, the role of mitochondrial and nuclear genes in sex determination has yet to be validated in DUI bivalves. In this study, we used DNA, RNA, and mitochondrial short non-coding RNA (sncRNA) sequencing to explore the role of mitochondrial and nuclear elements in the sexual development pathway of the freshwater musselPotamilus streckersoni(Bivalvia: Unionida). We found that the M mtDNA shed a sncRNA partially within a male-specific mitochondrial gene that targeted pathways hypothesized to be involved in female development and mitophagy. RNA-seq confirmed the gene target was significantly upregulated in females, supporting a direct role of mitochondrial sncRNAs in gene silencing. These findings support the hypothesis that M mtDNA inhibits female development. Genome-wide patterns of genetic differentiation and heterozygosity did not support a nuclear sex determining region, although we cannot reject that nuclear factors are involved with sex determination. Our results provide further evidence that mitochondrial loci contribute to diverse, non-respiratory functions and provide a first glimpse into an unorthodox sex determining system.
Exploring multi-omics latent embedding spaces for characterizing tumor heterogeneity and tumoral fitness effects
Authors: Wang Fengao , Liu Junwei , Gao Feng , Li Yixue 
Published: July 2023

AbstractThe ecological and evolutionary perspectives of tumorigenesis can be characterized as a process of microevolution in tumor cells that altered the tumor microenvironment and further induced tumor cell proliferation, metastasis, and the death of tumor patients. Here, we introduced XgeneVAE, an interpretable unsupervised deep learning framework that quantified the semantic changes in multi-omics embedding space for characterizing the microevolution processes and fitness effects of heterogeneous tumor samples. We then validated that the scales of the latent embedding variances can reflect the differences in the overall survival of tumor patients, as well as their applications in uncovering the driving genomic alternations in different cancer types. These results confirmed that the XgeneVAE model can better represent the heterogeneity in distinct cancer types and as an interpretable model for understanding the fitness effects in tumorigenesis and their association with clinical outcomes.
MulticomponentAyurvedaformulationLodhrasavamameliorates steatosis and lipotoxicity in HepG2 cell model of NAFLD
Authors: Kouser Sania , Banvi Pranav Girish , Garawadmath Soumya , Kumar Subrahmanya , Vishnuprasad Chethala N 
Published: July 2023

AbstractBackgroundNon-alcoholic fatty liver disease (NAFLD) is a complex, multifactorial and multi-system disorder. It is one of the major contributors of liver disease worldwide. Among the many factors involved in the pathogenesis of NAFLD, free fatty acids (FFAs) such as palmitic acid induced lipotoxicity promotes steatosis, oxidative stress and insulin resistance that activate apoptotic cascades leading to tissue damage and inflammation. Since NAFLD is a multifactorial metabolic disorder, conventional target-based drug therapies have limited success. Therefore, the use of multicomponent ayurveda herbal formulations could be a promising alternative due to their multitargeted mechanisms of action. The present study investigates the effects and underlying mechanism of actions of an ayurveda formulation,Lodhrasavam(TDU-LS-1), in the in-vitro model of NAFLD.MethodsLipotoxicity was induced in HepG2 cells by treating the cells with 1mM palmitic acid for 24 hrs followed by drug (TDU-LS-1) treatment for another 24 hrs. The effect of TDU-LS-1 on lipotoxicity was evaluated by MTT assay. The effect of TDU-LS-1 on steatosis was studied by estimating intracellular triglycerides, lipid droplets formation and expression of genes involved in lipid metabolism. Further, to examine the antioxidant activity, DPPH scavenging assay was performed.Results/discussionTDU-LS-1 was found to increase the antioxidant activity in a concentration dependent manner with an IC50 of 16.45 μg GAE/ml. Palmitic acid induced lipotoxicity in HepG2 cells was reduced by lower concentrations of TDU-LS-1. Also, the results from triglyceride (TAG) assay, Oil-Red-O staining and BODIPY 493/503 confocal imaging suggest that TDU-LS-1 reduces the palmitate induced triglyceride deposition and lipid droplet accumulation in HepG2 cells. Further, the qRT-PCR analysis of TDU-LS-1 at a concentration of 32 μg/GAE revealed that it modulates the expression of SREBP, FASN, SCD1, ACOX, and PPARγ that are relevant in hepatic lipid metabolism. Our results suggest that TDU-LS-1 can reducede novolipogenesis, peroxisomal lipid peroxidation as well as lipotoxicity in thein vitropalmitate-induced NAFLD model in HePG2 cells.