bluuebunny/crossref_metadata_2025_split huggingface dataset:
Free fatty acids and peripheral blood mononuclear cells (PBMC) are correlated with chronic inflammation in obesity
Authors: Liqiang Su , Fang-Hui Li , Minghui Quan , Yanan Yang , Haichun Chen 
Published: July 2023

Abstract
Obesity-related chronic inflammation is closely related to the ability of immune cells to adapt to the body’s needs, research has shown that excess FAs can further activate pro-inflammatory transcription factors in the nucleus by interacting with various receptors such as CD36 and TLR4, thereby affecting the inflammatory state of cells. However, how the profile of various fatty acids in the blood of obese individuals is associated with chronic inflammation remains unclear.

Objective
The biomarkers associated with obesity were identified from 40 fatty acids (FAs) in the blood, and analyze the relationship between the biomarkers and chronic inflammation. Furthermore, by analyzing the difference in the expression of CD36, TLR4 and NF-κB p65 in peripheral blood mononuclear cells (PBMC) between obese and standard weight people, understand that immunophenotype PBMC is associated with chronic inflammation.

Methods
This study is a cross-sectional study. Participants were recruited from the Yangzhou Lipan weight loss training camp from May 2020 to July 2020. The sample size was 52 individuals, including 25 in the normal weight group and 27 in the obesity group. Individuals with obesity and controls of normal weight were recruited to identify biomarkers associated with obesity from 40 fatty acids in the blood; correlation analysis was conducted between the screened potential biomarkers FAs and the chronic inflammation index hs-CRP to identify FA biomarkers associated with chronic inflammation. Changes in the fatty acid receptor CD36, inflammatory receptor TLR4, and inflammatory nuclear transcription factor NF-κB p65 in PBMC subsets were used to further test the relationship between fatty acids and the inflammatory state in individuals with obesity.

Results
23 potential FA biomarkers for obesity were screened, eleven of the potential obesity biomarkers were also significantly related to hs-CRP. Compared to the control group, in monocytes the obesity group expressed higher TLR4, CD36, and NF-κB p65 in lymphocytes, the obesity group expressed higher TLR4 and CD36; and in granulocytes the obesity group expressed higher CD36.

Conclusion
Blood FAs are associated with obesity and are associated with chronic inflammation through increased CD36, TLR4, and NF-κB p65 in monocytes.
Detection of β-amyloid aggregates/plaques in 5xFAD mice by labelled native PLGA nanoparticles: implication in the diagnosis of Alzheimer’s disease
Authors: Govindarajan Karthivashan , Kar Satyabrata 
Published: July 2023

AbstractEvidence suggests that increased level/aggregation of β-amyloid (Aβ) peptide, together with enhanced phosphorylation/aggregation of tau protein, play a critical role in the development of Alzheimer’s disease (AD), the leading cause of dementia in the elderly. At present, AD diagnosis is based primarily on cognitive assessment, neuroimaging, and immunological assays to detect altered levels/deposition of Aβ peptides and tau protein. While measurement of Aβ and tau in the cerebrospinal fluid/blood can indicate disease status, neuroimaging of aggregated Aβ and tau protein in the brain using positron emission tomography (PET) enable to monitor the pathological changes in AD patients. With advancements in nanomedicine, several nanoparticles, apart from drug-delivery, have been used as a diagnostic agent to identify more accurately changes in AD patients. Recently, we reported that FDA approved native PLGA nanoparticles can interact with Aβ to inhibit its aggregation/toxicity in cellular and animal models of AD. Here, we reveal that fluorescence labelled native PLGA following acute intracerebellar injection can identify majority of the immunostained Aβ as well as Congo red labelled neuritic plaques in the cortex of 5xFAD mice. Labelling of plaques by PLGA is apparent at 1 h, peak around 3 h and then start declining by 24 h after injection. No fluorescent PLGA was detected in the cerebellum of 5xFAD mice or in any brain regions of wild-type control mice following injection. These results provide the very first evidence that native PLGA nanoparticles can be used as a novel nano-theragnostic agent in the treatment as well as diagnosis of AD pathology.
Clinical profile and prognosis of elderly patients with left ventricular thrombus after anticoagulation
Authors: Zhang Qian , Zhang Zhongfan , Zheng Haikuo , Wang Chengbing , Yu Miao , Si Daoyuan , Zhang Wenqi 
Published: July 2023

Abstract
Background
Contemporary data regarding the clinical characteristics and prognosis of left ventricular thrombus (LVT) in older adults (aged ≥ 65 years old) are lacking. In this study, we characterized elderly patients with LVT (aged ≥ 65 years old) and investigated the long-term prognosis in this highly vulnerable patient population.

Methods
This single-center, retrospective study was conducted from January 2017 to December 2022. Patients with a reported LVT were assessed primarily by transthoracic echocardiography (TEE) and classified into two groups: elderly LVT groups and younger LVT groups. All patients were treated with anticoagulant treatment. Major adverse cardiovascular event (MACE) was defined as the composite of all-cause mortality, systemic embolism, and rehospitalization for cardiovascular events. Survival analyses were performed with the Kaplan-Meier method and Cox proportional-hazard model.

Results
A total of 315 eligible patients were included. Compared to the younger LVT group (n = 171), the elderly LVT group (n = 144) had a lower proportion of males and lower serum creatinine clearance, as well as a higher level of NT-proBNP, and a higher rate of history of systemic embolism. LVT resolution occurred in 59.7% and 69.0% of patients in the elderly LVT group and younger LVT group, respectively, with no significant difference (adjusted HR, 0.97; 95% CI, 0.74–1.28; P = 0.836). Yet, elderly patients with LVT, had higher prevalence rates of MACE (adjusted HR, 1.52; 95% CI, 1.10–2.11; P = 0.012), systemic embolism (adjusted HR, 2.81; 95% CI, 1.20–6.59; P = 0.017) and all-cause mortality (adjusted HR, 2.20; 95% CI, 1.29–3.74; P = 0.004) compared with younger patients with LVT. After adjusting for mortality in the Fine–Gray model, similar results were observed. Additionally, patients treated with different anticoagulation therapies (DOACs vs. warfarin) achieved a similar improvement in prognosis (P > 0.05) or LVT resolution (P > 0.05) in elderly patients with LVT.

Conclusions
Our results found that elderly patients experiencing LVT have a poor prognosis compared with the younger ones. Clinical prognosis in elderly patients did not significantly differ with the type of anticoagulant used. With aging societies worldwide, further evidence of antithrombotic therapy in elderly individuals with LVT is necessary.
Health data hubs: an analysis of existing data governance features for research
Authors: Alvarez-Romero Celia , Martínez-García Alicia , Bernabeu-Wittel Máximo , Parra-Calderón Carlos Luis 
Published: July 2023

Abstract
Background
Digital transformation in healthcare and the growth of health data generation and collection are important challenges for the secondary use of healthcare records in the health research field. Likewise, due to the ethical and legal constraints for using sensitive data, understanding how health data are managed by dedicated infrastructures called data hubs is essential to facilitating data sharing and reuse.

Methods
To capture the different data governance behind health data hubs across Europe, a survey focused on analysing the feasibility of linking individual-level data between data collections and the generation of health data governance patterns was carried out. The target audience of this study was national, European, and global data hubs. In total, the designed survey was sent to a representative list of 99 health data hubs in January 2022.

Results
In total, 41 survey responses received until June 2022 were analysed. Stratification methods were performed to cover the different levels of granularity identified in some data hubs’ characteristics. Firstly, a general pattern of data governance for data hubs was defined. Afterward, specific profiles were defined, generating specific data governance patterns through the stratifications in terms of the kind of organization (centralized versus decentralized) and role (data controller or data processor) of the health data hub respondents.

Conclusions
The analysis of the responses from health data hub respondents across Europe provided a list of the most frequent aspects, which concluded with a set of specific best practices on data management and governance, taking into account the constraints of sensitive data. In summary, a data hub should work in a centralized way, providing a Data Processing Agreement and a formal procedure to identify data providers, as well as data quality control, data integrity and anonymization methods.
The B56γ3-containing protein phosphatase 2A attenuates p70S6K-mediated negative feedback loop to enhance AKT-facilitated epithelial-mesenchymal transition in colorectal cancer
Authors: Hsiao Kai-Ching , Ruan Siou-Ying , Chen Shih-Min , Lai Tai-Yu , Chan Ren-Hao , Zhang Yan-Ming , Chu Chien-An , Cheng Hung-Chi , Tsai Hung-Wen , Tu Yi-Fang , Law Brian K. , Chang Ting-Tsung , Chow Nan-Haw , Chiang Chi-Wu 
Published: July 2023

Abstract
Background
Protein phosphatase 2A (PP2A) is one of the major protein phosphatases in eukaryotic cells and is essential for cellular homeostasis. PP2A is a heterotrimer comprising the dimeric AC core enzyme and a highly variable regulatory B subunit. Distinct B subunits help the core enzyme gain full activity toward specific substrates and contribute to diverse cellular roles of PP2A. PP2A has been thought to play a tumor suppressor and the B56γ3 regulatory subunit was shown to play a key tumor suppressor regulatory subunit of PP2A. Nevertheless, we uncovered a molecular mechanism of how B56γ3 may act as an oncogene in colorectal cancer (CRC).

Methods
Polyclonal pools of CRC cells with stable B56γ3 overexpression or knockdown were generated by retroviral or lentiviral infection and subsequent drug selection. Co-immunoprecipitation(co-IP) and in vitro pull-down analysis were applied to analyze the protein–protein interaction. Transwell migration and invasion assays were applied to investigate the role of B56γ3 in affecting motility and invasive capability of CRC cells. The sensitivity of CRC cells to 5-fluorouracil (5-FU) was analyzed using the PrestoBlue reagent assay for cell viability. Immunohistochemistry (IHC) was applied to investigate the expression levels of phospho-AKT and B56γ3 in paired tumor and normal tissue specimens of CRC. DataSets of TCGA and GEO were analyzed to investigate the correlation of B56γ3 expression with overall survival rates of CRC patients.

Results
We showed that B56γ3 promoted epithelial-mesenchymal transition (EMT) and reduced the sensitivity of CRC cells to 5-FU through upregulating AKT activity. Mechanistically, B56γ3 upregulates AKT activity by targeting PP2A to attenuate the p70S6K-mediated negative feedback loop regulation on PI3K/AKT activation. B56γ3 was highly expressed and positively correlated with the level of phospho-AKT in tumor tissues of CRC. Moreover, high B56γ3 expression is associated with poor prognosis of a subset of patients with CRC.

Conclusions
Our finding reveals that the B56γ3 regulatory subunit-containing PP2A plays an oncogenic role in CRC cells by sustaining AKT activation through suppressing p70S6K activity and suggests that the interaction between B56γ3 and p70S6K may serve as a therapeutic target for CRC.
Extracellular vesicle-associated tyrosine kinase-like orphan receptors ROR1 and ROR2 promote breast cancer progression
Authors: Irmer Barnabas , Efing Janes , Reitnauer Lea Elisabeth , Angenendt Allegra , Heinrichs Saskia , Schubert Antonia , Schulz Matthias , Binder Claudia , Tio Joke , Hansen Uwe , Geyer Christiane , Gerwing Mirjam , Bleckmann Annalen , Menck Kerstin 
Published: July 2023

Abstract
Background
Extracellular vesicles (EVs) harbor a plethora of different biomolecules, which they can transport across cells. In cancer, tumor-derived EVs thereby support the creation of a favorable tumor microenvironment. So far, EV uptake and cargo delivery into target cells have been regarded as the main mechanisms for the pro-tumoral function of EVs. To test this hypothesis, we investigated the fate of the oncogenic transmembrane Wnt tyrosine kinase-like orphan receptor 1 and 2 (ROR1, ROR2) delivered via distinct EV subpopulations to breast cancer cells and aimed to unravel their impact on tumor progression.

Methods
EVs were isolated by differential ultracentrifugation from cell culture supernatant as well as plasma samples from healthy individuals (n = 27) and breast cancer patients (n = 41). EVs were thoroughly characterized by electron microscopy, nanoparticle tracking analysis, immunoblot, and flow cytometry. ROR transfer to target cells was observed using microscopy-based assays and biodistribution experiments were conducted in syngeneic mice. EV impact on cancer cell migration and invasion was tested in functional assays.

Results
We observed that the supernatant of ROR-overexpressing cells was sufficient for transferring the receptors to ROR-negative cells. Analyzing the secretome of the ROR-overexpressing cells, we detected a high enrichment of ROR1/2 on large and small EVs, but not on large oncosomes. Interestingly, the majority of ROR-positive EVs remained attached to the target cell surface after 24 h of stimulation and was quickly removed by treatment with trypsin. Nonetheless, ROR-positive EVs increased migration and invasion of breast cancer cells, even after chemically inhibiting EV uptake, in dependence of RhoA downstream signaling. In vivo, ROR-depleted EVs tended to distribute less into organs prone for the formation of breast cancer metastases. ROR-positive EVs were also significantly elevated in the plasma of breast cancer patients and allowed to separate them from healthy controls.

Conclusions
The oncogenic Wnt receptors ROR1/2 are transferred via EVs to the surface of ROR-negative cancer cells, in which they induce an aggressive phenotype supporting tumor progression.
Cost analysis and cost effectiveness of a subsidized community supported agriculture intervention for low-income families
Authors: Garner Jennifer A. , Hanson Karla L. , Jilcott Pitts Stephanie B. , Kolodinsky Jane , Sitaker Marilyn H. , Ammerman Alice S. , Kenkel Donald , Seguin-Fowler Rebecca A. 
Published: July 2023

Abstract
Background
The food system has a dynamic influence on disparities in food security and diet-related chronic disease. Community supported agriculture (CSA) programs, in which households receive weekly shares of produce from a local farmer during the growing season, have been examined as a possible food systems-based approach for improving diet and health outcomes. The purpose of this study was to estimate the cost of implementing and participating in a multi-component subsidized community supported agriculture intervention and calculate cost-effectiveness based on diet and food security impacts.

Methods
Using data from the Farm Fresh Foods for Healthy Kids (F3HK) randomized controlled trial in New York, North Carolina, Vermont, and Washington (n = 305; 2016–2018), we estimated programmatic and participant costs and calculated incremental cost-effectiveness ratios (ICERs) for caregivers’ daily fruit and vegetable (FV) intake, skin carotenoids, and household food security from program and societal perspectives.

Results
F3HK cost $2,439 per household annually ($1,884 in implementation-related expenses and $555 in participant-incurred costs). ICERs ranged from $1,507 to $2,439 per cup increase in caregiver’s FV intake (depending on perspective, setting, and inclusion of juice); from $502 to $739 per one thousand unit increase in skin carotenoid score; and from $2,271 to $3,137 per household shifted out of food insecurity.

Conclusions
Given the known public health, healthcare, and economic consequences of insufficient FV intake and living in a food insecure household, the costs incurred to support these positive shifts in individual- and household-level outcomes via a F3HK-like intervention may be deemed by stakeholders as a reasonable investment. This work helps to advance a critical body of literature on the cost-effectiveness of subsidized CSAs and other economic and food system interventions for the sake of evidence-based allocation of public health resources.

Trial registration
: ClinicalTrials.gov. NCT02770196. Registered 5 April 2016. Retrospectively registered. https://www.clinicaltrials.gov/ct2/show/NCT02770196.
Eulertigs: minimum plain text representation of k-mer sets without repetitions in linear time
Authors: Schmidt Sebastian , Alanko Jarno N. 
Published: July 2023

AbstractA fundamental operation in computational genomics is to reduce the input sequences to their constituentk-mers. For maximum performance of downstream applications it is important to store thek-mers in small space, while keeping the representation easy and efficient to use (i.e. withoutk-mer repetitions and in plain text). Recently, heuristics were presented to compute a near-minimum such representation. We present an algorithm to compute a minimum representation in optimal (linear) time and use it to evaluate the existing heuristics. Our algorithm first constructs the de Bruijn graph in linear time and then uses a Eulerian-cycle-based algorithm to compute the minimum representation, in time linear in the size of the output.
COVID-19 and spontaneous pneumothorax: a survival analysis
Authors: Ershadi Reza , Rafieian Shahab , Salehi Mohammadreza , Kazemizadeh Hossein , Amini Hesam , Sohrabi Marjan , Samimiat Alireza , Sharafi Yaser , Dashtkoohi Mohadese , Vahedi Matin 
Published: July 2023

Abstract
Introduction
COVID-19 Patients may be at risk for involving with spontaneous pneumothorax. However, clinical data are lacking in this regard. In this study, we aimed to investigate the demographic, clinical, and radiological characteristics and survival predictors in COVID-19 patients with pneumothorax.

Methods
This is a retrospectivestudy conducted on COVID-19 patients with pneumothorax that had been hospitalized at hospital. l from December 2021 to March 2022. The chest computed tomography (CT) scan of all patients was reviewed by an experienced pulmonologist in search of pulmonary pneumothorax. Survival analysis was conducted to identify the predictors of survival in patients with COVID-19 and pneumothorax.

Results
A total of 67 patients with COVID-19 and pneumothorax were identified. Of these, 40.7% were located in the left lung, 40.7% were in the right lung, and 18.6% were found bilaterally. The most common symptoms in the patient with pneumothorax were dyspnea (65.7%), increased cough severity (53.7%), chest pain (25.4%), and hemoptysis (16.4%). The frequency of pulmonary left and right bullae, pleural effusion, andfungus ball were 22.4%, 22.4%, 22.4%, and 7.5%, respectively. Pneumothorax was managed with chest drain (80.6%), chest drain and surgery (6%), and conservatively (13.4%). The 50-day mortality rate was 52.2% (35 patients). The average survival time for deceased patients was 10.06 (2.17) days.

Conclusions
Our results demonstrated that those with pleural effusion or pulmonary bullae have a lower survival rate. Further studies are required to investigate the incidence and causality relation between COVID-19 and pneumothorax.
Variability of toe pressures during haemodialysis: comparison of people with and without diabetes; a pilot study
Authors: Carle Rachel , Tehan Peta , Stewart Sarah , Semple David , Pilmore Andrew , Carroll Matthew R. 
Published: July 2023

AbstractBackgroundDiabetes, end stage renal disease (ESRD), and peripheral arterial disease (PAD) are associated with a higher risk of diabetes‐related lower limb amputation. Timely identification of PAD with toe systolic blood pressure (TSBP) and toe‐brachial pressure index (TBPI) is critical in order to implement foot protection strategies to prevent foot complications in people with ESRD. There is limited evidence describing the effect of haemodialysis on TSBP and TBPI. This study aimed to determine the variability of TSBP and TBPI during haemodialysis in people with ESRD, and to determine whether any observed variability differed between people with and without diabetes.MethodsTSBP and TBPI were taken before dialysis (T1), one hour into dialysis (T2) and in the last 15 min of dialysis (T3) during a single dialysis session. Linear mixed effects models were undertaken to determine the variability in TSBP and TBPI across the three time points and to determine whether this variability differed between people with and without diabetes.ResultsThirty participants were recruited, including 17 (57%) with diabetes and 13 (43%) with no diabetes. A significant overall reduction in TSBP was observed across all participants (P < 0.001). There was a significant reduction in TSBP between T1 and T2 (P < 0.001) and between T1 and T3 (P < 0.001). There was no significant overall change in TBPI over time (P = 0.62). There was no significant overall difference in TSBP between people with diabetes and people with no diabetes (mean difference [95% CI]: ‐9.28 [‐40.20, 21.64], P = 0.54). There was no significant overall difference in TBPI between people with diabetes and people with no diabetes (mean difference [95% CI]: ‐0.01 [‐0.17, 03.16], P = 0.91).ConclusionTSBP and TBPI are an essential part of vascular assessment of the lower limb. TBPI remained stable and TSBP significantly reduced during dialysis. Given the frequency and duration of dialysis, clinicians taking toe pressures to screen for PAD should be aware of this reduction and consider how this may have an impact on wound healing capacity and the development of foot related complications.