bluuebunny/crossref_metadata_2025_split huggingface dataset:
The lipidomic profile of the tumoral periprostatic adipose tissue reveals alterations in tumor cell’s metabolic crosstalk
Authors: Altuna-Coy Antonio , Ruiz-Plazas Xavier , Sánchez-Martin Silvia , Ascaso-Til Helena , Prados-Saavedra Manuel , Alves-Santiago Marta , Bernal-Escoté Xana , Segarra-Tomás José , R. Chacón Matilde 
Published: August 2022

Abstract

Background
Periprostatic adipose tissue (PPAT) plays a role in prostate cancer (PCa) progression. PPAT lipidomic composition study may allow us to understand the tumor metabolic microenvironment and provide new stratification factors.

Methods
We used ultra-high-performance liquid chromatography-mass spectrometry-based non-targeted lipidomics to profile lipids in the PPAT of 40 patients with PCa (n = 20 with low-risk and n = 20 high-risk). Partial least squares-discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify the most relevant features of PPAT between low- and high-risk PCa, and metabolite set enrichment analysis was used to detect disrupted metabolic pathways. Metabolic crosstalk between PPAT and PCa cell lines (PC-3 and LNCaP) was studied using ex vivo experiments. Lipid uptake and lipid accumulation were measured. Lipid metabolic-related genes (SREBP1, FASN, ACACA, LIPE, PPARG, CD36, PNPLA2, FABP4, CPT1A, FATP5, ADIPOQ), inflammatory markers (IL-6, IL-1B, TNFα), and tumor-related markers (ESRRA, MMP-9, TWIST1) were measured by RT-qPCR.

Results
Significant differences in the content of 67 lipid species were identified in PPAT samples between high- and low-risk PCa. PLS-DA and VIP analyses revealed a discriminating lipidomic panel between low- and high-risk PCa, suggesting the occurrence of disordered lipid metabolism in patients related to PCa aggressiveness. Functional analysis revealed that alterations in fatty acid biosynthesis, linoleic acid metabolism, and β-oxidation of very long-chain fatty acids had the greatest impact in the PPAT lipidome. Gene analyses of PPAT samples demonstrated that the expression of genes associated with de novo fatty acid synthesis such as FASN and ACACA were significantly lower in PPAT from high-risk PCa than in low-risk counterparts. This was accompanied by the overexpression of inflammatory markers (IL-6, IL-1B, and TNFα). Co-culture of PPAT explants with PCa cell lines revealed a reduced gene expression of lipid metabolic-related genes (CD36, FASN, PPARG, and CPT1A), contrary to that observed in co-cultured PCa cell lines. This was followed by an increase in lipid uptake and lipid accumulation in PCa cells. Tumor-related genes were increased in co-cultured PCa cell lines.

Conclusions
Disturbances in PPAT lipid metabolism of patients with high-risk PCa are associated with tumor cell metabolic changes.
Mesenchymal stem cells protect against TBI-induced pyroptosis in vivo and in vitro through TSG-6
Authors: Feng Zhiming , Hua Shiting , Li Wangan , Han Jianbang , Li Feng , Chen Haijia , Zhang Zhongfei , Xie Yu , Ouyang Qian , Zou Xiaoxiong , Liu Zhizheng , Li Cong , Huang Sixian , Lai Zelin , Cai Xiaolin , Cai Yingqian , Zou Yuxi , Tang Yanping , Jiang Xiaodan 
Published: August 2022

Abstract
Background
Pyroptosis, especially microglial pyroptosis, may play an important role in central nervous system pathologies, including traumatic brain injury (TBI). Transplantation of mesenchymal stem cells (MSCs), such as human umbilical cord MSCs (hUMSCs), has been a focus of brain injury treatment. Recently, MSCs have been found to play a role in many diseases by regulating the pyroptosis pathway. However, the effect of MSC transplantation on pyroptosis following TBI remains unknown. Tumor necrosis factor α stimulated gene 6/protein (TSG-6), a potent anti-inflammatory factor expressed in many cell types including MSCs, plays an anti-inflammatory role in many diseases; however, the effect of TSG-6 secreted by MSCs on pyroptosis remains unclear.

Methods
Mice were subjected to controlled cortical impact injury in vivo. To assess the time course of pyroptosis after TBI, brains of TBI mice were collected at different time points. To study the effect of TSG-6 secreted by hUMSCs in regulating pyroptosis, normal hUMSCs, sh-TSG-6 hUMSCs, or different concentrations of rmTSG-6 were injected intracerebroventricularly into mice 4 h after TBI. Neurological deficits, double immunofluorescence staining, presence of inflammatory factors, cell apoptosis, and pyroptosis were assessed. In vitro, we investigated the anti-pyroptosis effects of hUMSCs and TSG-6 in a lipopolysaccharide/ATP-induced BV2 microglial pyroptosis model.

Results
In TBI mice, the co-localization of Iba-1 (marking microglia/macrophages) with NLRP3/Caspase-1 p20/GSDMD was distinctly observed at 48 h. In vivo, hUMSC transplantation or treatment with rmTSG-6 in TBI mice significantly improved neurological deficits, reduced inflammatory cytokine expression, and inhibited both NLRP3/Caspase-1 p20/GSDMD expression and microglial pyroptosis in the cerebral cortices of TBI mice. However, the therapeutic effect of hUMSCs on TBI mice was reduced by the inhibition of TSG-6 expression in hUMSCs. In vitro, lipopolysaccharide/ATP-induced BV2 microglial pyroptosis was inhibited by co-culture with hUMSCs or with rmTSG-6. However, the inhibitory effect of hUMSCs on BV2 microglial pyroptosis was significantly reduced by TSG-6-shRNA transfection.

Conclusion
In TBI mice, microglial pyroptosis was observed. Both in vivo and in vitro, hUMSCs inhibited pyroptosis, particularly microglial pyroptosis, by regulating the NLRP3/Caspase-1/GSDMD signaling pathway via TSG-6.
Total mutational load and clinical features as predictors of the metastatic status in lung adenocarcinoma and squamous cell carcinoma patients
Authors: Oróstica Karen Y. , Saez-Hidalgo Juan , de Santiago Pamela R. , Rivas Solange , Contreras Sebastian , Navarro Gonzalo , Asenjo Juan A. , Olivera-Nappa Álvaro , Armisén Ricardo 
Published: August 2022

Abstract
Background
Recently, extensive cancer genomic studies have revealed mutational and clinical data of large cohorts of cancer patients. For example, the Pan-Lung Cancer 2016 dataset (part of The Cancer Genome Atlas project), summarises the mutational and clinical profiles of different subtypes of Lung Cancer (LC). Mutational and clinical signatures have been used independently for tumour typification and prediction of metastasis in LC patients. Is it then possible to achieve better typifications and predictions when combining both data streams?

Methods
In a cohort of 1144 Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Carcinoma (LSCC) patients, we studied the number of missense mutations (hereafter, the Total Mutational Load TML) and distribution of clinical variables, for different classes of patients. Using the TML and different sets of clinical variables (tumour stage, age, sex, smoking status, and packs of cigarettes smoked per year), we built Random Forest classification models that calculate the likelihood of developing metastasis.

Results
We found that LC patients different in age, smoking status, and tumour type had significantly different mean TMLs. Although TML was an informative feature, its effect was secondary to the "tumour stage" feature. However, its contribution to the classification is not redundant with the latter; models trained using both TML and tumour stage performed better than models trained using only one of these variables. We found that models trained in the entire dataset (i.e., without using dimensionality reduction techniques) and without resampling achieved the highest performance, with an F1 score of 0.64 (95%CrI [0.62, 0.66]).

Conclusions
Clinical variables and TML should be considered together when assessing the likelihood of LC patients progressing to metastatic states, as the information these encode is not redundant. Altogether, we provide new evidence of the need for comprehensive diagnostic tools for metastasis.
3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) Positron Emission Tomography as an In Vivo Biomarker of inhibition of CDK 4/6-Rb pathway by Palbociclib in a patient derived bladder tumor
Authors: Tatum James L. , Kalen Joseph D. , Jacobs Paula M. , Riffle Lisa A. , James Amy , Thang Lai , Sanders Chelsea , Hollingshead Melinda G. , Basuli Falguni , Shi Jianfeng , Doroshow James H. 
Published: August 2022

Abstract
Background
Several new generation CDK4/6 inhibitors have been developed and approved for breast cancer therapy in combination with endocrine therapeutics. Application of these inhibitors either alone or in combination in other solid tumors has been proposed, but no imaging biomarkers of response have been reported in non-breast cancer animal models. The purpose of this study was to evaluate 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) Positron Emission Tomography (PET) as in vivo biomarker of response to palbociclib in a non-breast cancer model.

Methods
Twenty-four NSG mice bearing patient derived xenografts (PDX) of a well-characterized bladder tumor were randomized into 4 treatment groups: vehicle (n = 6); palbociclib (n = 6); temozolomide (n = 6); and palbociclib plus temozolomide (n = 6) and treated with two cycles of therapy or vehicle. Tumor uptake of [18F]FLT was determined by micro-PET/CT at baseline, 3 days, and 9 days post initiation of therapy. Following the second cycle of therapy, the mice were maintained until their tumors reached a size requiring humane termination.

Results
[18F]FLT uptake decreased significantly in the palbociclib and combination arms (p = 0.0423 and 0.0106 respectively at day 3 and 0.0012 and 0.0031 at day 9) with stable tumor volume. In the temozolomide arm [18F]FLT uptake increased with day 9 uptake significantly different than baseline (p = 0.0418) and progressive tumor growth was observed during the treatment phase. All groups exhibited progressive disease after day 22, 10 days following cessation of therapy.

Conclusion
Significant decreases in [18F]FLT uptake as early as three days post initiation of therapy with palbociclib, alone or in combination with temozolomide, in this bladder cancer model correlates with an absence of tumor growth during therapy that persists until day 18 for the palbociclib group and day 22 for the combination group (6 days and 10 days) following cessation of therapy. These results support early modulation of [18F]FLT as an in vivo biomarker predictive of palbociclib therapy response in a non-breast cancer model.
Serum trimethylamine-N-oxide is associated with incident type 2 diabetes in middle-aged and older adults: a prospective cohort study
Authors: Li Shu-yi , Chen Si , Lu Xiao-ting , Fang Ai-ping , Chen Yu-ming , Huang Rong-zhu , Lin Xin-lei , Huang Zi-hui , Ma Jing-fei , Huang Bi-xia , Zhu Hui-lian 
Published: August 2022

AbstractBackgroundThe role of trimethylamine-N-oxide (TMAO) in the development of diabetes remains controversial, and prospective data are few. We aimed to investigate the association between serum TMAO and incident type 2 diabetes in middle-aged and older adults.MethodsThis study was based on the Guangzhou Nutrition and Health Study (GNHS), a community-based prospective cohort study in China. A total of 2088 diabetes-free participants aged 40–75 years were included from 2008 to 2010. Incident type 2 diabetes was ascertained during follow-up visits. Baseline serum TMAO was measured by high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for diabetes across tertiles of serum TMAO were calculated using Cox proportional hazard models. Prospective associations of serum TMAO with changes in glycemic traits (fasting glucose, HbA1c, insulin, HOMA-IR) over time were estimated using linear mixed-effects models (LMEMs).ResultsWe ascertained 254 incident type 2 diabetes cases during a median follow-up of 8.9 years. The median (interquartile range) of serum TMAO was 1.54 (0.86–2.91) μmol/L. From the first to the third tertile of serum TMAO, the multivariable-adjusted HRs for diabetes were 1.00 (reference), 1.17 (95% CI: 0.84–1.61), and 1.42 (95% CI: 1.03–1.96) (P-trend = 0.031). LMEMs showed that the estimated yearly change in fasting glucose was 0.011 (0.001–0.022) mmol/L/y in the highest tertile of serum TMAO, compared with the lowest tertile (P-interaction = 0.044). Serum TMAO was not associated with longitudinal changes in HbA1c, insulin or HOMA-IR.ConclusionsOur findings suggested that higher serum TMAO was associated with a higher risk of type 2 diabetes and an increase in fasting glucose among middle-aged and older Chinese adults.Trial registration:NCT03179657.https://clinicaltrials.gov/ct2/show/NCT03179657?term=NCT03179657&draw=2&rank=1
Candida and the Gram-positive trio: testing the vibe in the ICU patient microbiome using structural equation modelling of literature derived data
Authors: Hurley James C. 
Published: August 2022

Abstract
Background
Whether Candida interacts with Gram-positive bacteria, such as Staphylococcus aureus, coagulase negative Staphylococci (CNS) and Enterococci, to enhance their invasive potential from the microbiome of ICU patients remains unclear. Several effective anti-septic, antibiotic, anti-fungal, and non-decontamination based interventions studied for prevention of ventilator associated pneumonia (VAP) and other ICU acquired infections among patients receiving prolonged mechanical ventilation (MV) are known to variably impact Candida colonization. The collective observations within control and intervention groups from numerous ICU infection prevention studies enables tests of these postulated microbial interactions in the clinical context.

Methods
Four candidate generalized structural equation models (GSEM), each with Staphylococcus aureus, CNS and Enterococci colonization, defined as latent variables, were confronted with blood culture and respiratory tract isolate data derived from 460 groups of ICU patients receiving prolonged MV from 283 infection prevention studies.

Results
Introducing interaction terms between Candida colonization and each of S aureus (coefficient + 0.40; 95% confidence interval + 0.24 to + 0.55), CNS (+ 0.68; + 0.34 to + 1.0) and Enterococcal (+ 0.56; + 0.33 to + 0.79) colonization (all as latent variables) improved the fit for each model. The magnitude and significance level of the interaction terms were similar to the positive associations between exposure to topical antibiotic prophylaxis (TAP) on Enterococcal (+ 0.51; + 0.12 to + 0.89) and Candida colonization (+ 0.98; + 0.35 to + 1.61) versus the negative association of TAP with S aureus (− 0.45; − 0.70 to − 0.20) colonization and the negative association of anti-fungal exposure and Candida colonization (− 1.41; − 1.6 to − 0.72).

Conclusions
GSEM modelling of published ICU infection prevention data enables the postulated interactions between Candida and Gram-positive bacteria to be tested using clinically derived data. The optimal model implies interactions occurring in the human microbiome facilitating bacterial invasion and infection. This interaction might also account for the paradoxically high bacteremia incidences among studies of TAP in ICU patients.
Cognitive rehabilitation in people with autism spectrum disorder: a systematic review of emerging virtual reality-based approaches
Authors: Shahmoradi Leila , Rezayi Sorayya 
Published: August 2022

AbstractIntroductionEmerging virtual technologies and cognitive rehabilitation methods are two new treatment approaches that can be used to strengthen cognitive functions in Autism Spectrum Disorder (ASD). The main aim of this study was to examine the effect of using virtual reality-based approaches on cognitive disorders of children and adults with ASD.MethodsThis systematic review was conducted on scientific papers to determine the effects of virtual reality-based technologies on the cognitive functions of children and adults with ASD. We identified 688 studies related to this topic and filtered them down to 17 articles, and then extracted the effects of interventions on cognitive outcomes.ResultsA total of 17 studies met the inclusion criteria, in which 226 persons with ASD had taken place. The sample size in the selected studies ranged from 1 to 56 participants (Median: 8, Q1: 3.5, Q3: 15.5). Four of the studies were case–control studies, ten were pre-test/post-test studies, and three were Randomized Control Trials (RCTs). Results of 16 studies showed significant progress in various cognitive indexes, such as task learning, attention, executive functioning, and daily skills in people with ASD. In most studies, virtual technologies had beneficial effects on reducing cognitive problems, but existing limitations could reduce their effectiveness. These limitations included the cost of virtual reality devices, inappropriate size of software, the weight of devices, potential addiction, intolerance of wearing glasses or headsets by people with autism (especially in children), and the possibility of eye injury.ConclusionApplying appropriate virtual-based approaches could improve cognitive indexes in people with ASD. However, further studies are needed to investigate the real effects of these technologies in the long run.
Vitamin D status and its correlation to depression
Authors: khan Bashir , Shafiq Huma , Abbas Seyyedha , Jabeen Summeira , Khan Sikandar Ali , Afsar Tayyaba , Almajwal Ali , Alruwaili Nawaf W. , al-disi Dara , Alenezi Sultan , Parveen Zahida , Razak Suhail 
Published: August 2022

Abstract
Background
Vitamin D can influence more than 200 genes in various tissues showing its credibility among the fat-soluble vitamins. Vitamin D deficiency is directly proportional to major clinical conditions such as cardiovascular diseases, diabetes, malignancy, and multiple sclerosis. This study was conducted to determine the vitamin D level of individuals and its association with depression.

Methods
Vitamin D levels of 100 healthy and 100 depressed subjects were determined. The isolated subjects were screened on the Beck Depression Inventory (BDI) scale and divided into three groups according to their age. Group-I comprised subjects of age 20 years and below, Group-II included subjects of age 21 to 60, and Group-III comprised subjects of ≥ 61 years of age. A sufficient level of vitamin D in normal subjects was noted, while mild deficiency of vitamin D status was observed in depressed subjects.

Results
Our study has reported a higher percentage of vitamin D deficiency in the Peshawar region. The results of our study indicated that depression was common in individuals having vitamin D deficiency.

Conclusions
The study showed a very high frequency of vitamin D deficiency in subjects with depression in Peshawar, Pakistan. The deficiency of vitamin D was observed more in females as compared to males. Further studies should explicate whether the highly widespread vitamin D deficiency could be cost-effectively treated as part of preventive or treatment interventions for depression.
CT guided autologous blood localization of pulmonary ground glass nodules for video assisted thoracoscopic surgery compared to micro-coil localization
Authors: Xu Jianxin , Si Tingting , Zheng Maohua , Guan Jun , Li Zhixin , Xu Zhiyang 
Published: August 2022

Abstract
Objectives
To investigate feasibility and safety of autologous blood in preoperative computed tomography (CT)-guided localization of pulmonary ground-glass nodules (GGNs) by comparing to mico-coil prior to video-assisted thoracoscopic surgery.

Methods
Clinical data of patients with GGNs who underwent video-assisted thoracoscopic surgery followed by preoperative CT-guided autologous blood or micro-coil localization was retrospectively reviewed in our department between September 2019 and November 2021. The localization duration, localization success rate, localization-related complication, localization cost, operation time, and conversion rate were compared between the 2 localization groups.

Results
Totally 65 patients with 65 GGNs were included in our study, with 34 patients in autologous blood group (group B) and 31 patients in micro-coil group (group M). There is no conversion to thoracotomy. The age, sex, nodule location, diameter of nodule and distance from the pleura between the 2 groups were statistically comparable. Compared with group M, group B had similar localization success rate (94.1% vs 83.9%, P = 0.183) but shorter localization time (14.50 ± 2.61 min vs 16.35 ± 2.30 min, P = 0.004), lower cost ($92.4 ± 3.2 vs $475.6 ± 8.5, P = 0.001), and lower incidence of puncture complications (3.0% vs 19.3%, P = 0.042).

Conclusions
The autologous blood localization is an effective and more economical method for preoperative GGNs localization, and is associated with fewer complications compared to micro-coil localization.
MiR-19b-3p regulated by BC002059/ABHD10 axis promotes cell apoptosis in myocardial infarction
Authors: Liao Bihong , Dong Shaohong , Xu Zhenglei , Gao Fei , Zhang Suihao , Liang Ruijuan 
Published: August 2022

Abstract
Background
Recently, microRNAs (miRNAs), have been extensively investigated in diseases. The upregulated expression of miR-19b-3p has been validated in patients with hypertrophic cardiomyopathy. Nonetheless, it regulatory mechanism in myocardial infarction (MI) is still unclear.

Purpose
This research aimed to investigate the role and molecular regulation mechanism of miR-19b-3p in MI.

Methods
QRT-PCR and western blot assays measured RNA and protein expression. Cell apoptosis were tested by flow cytometry and TUNEL assays. Cell viability was measured by trypan blue staining method. RIP and luciferase report assays examined gene interaction. The assays were performed under hypoxia condition.

Results
MiR-19b-3p was highly expressed in myocardial cell line H9C2, primary cardiomyocytes, and tissues from MI mouse model. MiR-19b-3p inhibition suppressed the apoptosis of cardiomyocytes. BC002059 could up-regulate ABHD10 through sequestering miR-19b-3p. BC002059 upregulation was observed to repress cell apoptosis. Rescue experiments demonstrated that miR-19b-3p overexpression abrogated the suppressive impact of BC002059 on the apoptosis of MI cells, and infarct size, area at risk as well as CK-MB and LDH release of MI mouse model tissues, which was further abolished via ABHD10 increment.

Conclusion
MiR-19b-3p regulated by BC002059/ABHD10 axis promotes cell apoptosis in MI, which might provide a novel perspective for MI alleviation research.