bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doxorubicin and CpG loaded liposomal spherical nucleic acid for enhanced Cancer treatment
Authors: Deng Bo , Ma Bing , Ma Yingying , Cao Pei , Leng Xigang , Huang Pengyu , Zhao Yuanyuan , Ji Tianjiao , Lu Xueguang , Liu Lanxia 
Published: March 2022

AbstractChemotherapeutics that can trigger immunogenic cell death (ICD) and release tumor-specific antigens are effective on treating a variety of cancers. The codelivery of chemotherapeutics with adjuvants is a promising strategy to achieve synergistic therapeutic effect. However, low drug loading and complicated preparation of current delivery systems lead to carrier-associated toxicity and immunogenicity. Herein, we developed a facile approach to construct liposomal spherical nucleic acids (SNA) by the self-assembly of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)-doxorubicin conjugate and DOPE-matrix metalloproteinases-9 (MMP-9) responsive peptide-CpG conjugate (DOPE-MMP-CpG). Liposomal SNAs efficiently co-delivered DOX and CpG into tumors and released the two drugs upon biological stimuli of MMP-9 enzyme in tumor microenvironment (TME) and high concentration of endogenous glutathione in tumor cells. We demonstrated that liposomal SNA enhanced activation of dendritic cells (DCs), promoted expansion of CD8+ and CD4+ T cells in both tumors and spleen, inhibited tumor growth, and extended animal survival. This work provided a simple strategy of delivering chemotherapeutics and adjuvants to tumors with synergistic therapeutic effect and reduced side effect.
Graphical Abstract
Role of store-operated Ca2+ entry in cardiovascular disease
Authors: Lu Ting , Zhang Yihua , Su Yong , Zhou Dayan , Xu Qiang 
Published: March 2022

AbstractStore-operated channels (SOCs) are highly selective Ca2+ channels that mediate Ca2+ influx in non-excitable and excitable (i.e., skeletal and cardiac muscle) cells. These channels are triggered by Ca2+ depletion of the endoplasmic reticulum and sarcoplasmic reticulum, independently of inositol 1,4,5-trisphosphate (InsP3), which is involved in cell growth, differentiation, and gene transcription. When the Ca2+ store is depleted, stromal interaction molecule1 (STIM1) as Ca2+ sensor redistributes into discrete puncta near the plasma membrane and activates the protein Ca2+ release activated Ca2+ channel protein 1 (Orai1). Accumulating evidence suggests that SOC is associated with several physiological roles in endothelial dysfunction and vascular smooth muscle proliferation that contribute to the progression of cardiovascular disease. This review mainly elaborates on the contribution of SOC in the vasculature (endothelial cells and vascular smooth muscle cells). We will further retrospect the literature implicating a critical role for these proteins in cardiovascular disease.
Graphical Abstract
A machine learning-based risk stratification tool for in-hospital mortality of intensive care unit patients with heart failure
Authors: Luo Cida , Zhu Yi , Zhu Zhou , Li Ranxi , Chen Guoqin , Wang Zhang 
Published: March 2022

Abstract
Background
Predicting hospital mortality risk is essential for the care of heart failure patients, especially for those in intensive care units.

Methods
Using a novel machine learning algorithm, we constructed a risk stratification tool that correlated patients’ clinical features and in-hospital mortality. We used the extreme gradient boosting algorithm to generate a model predicting the mortality risk of heart failure patients in the intensive care unit in the derivation dataset of 5676 patients from the Medical Information Mart for Intensive Care III database. The logistic regression model and a common risk score for mortality were used for comparison. The eICU Collaborative Research Database dataset was used for external validation.

Results
The performance of the machine learning model was superior to that of conventional risk predictive methods, with the area under curve 0.831 (95% CI 0.820–0.843) and acceptable calibration. In external validation, the model had an area under the curve of 0.809 (95% CI 0.805–0.814). Risk stratification through the model was specific when the hospital mortality was very low, low, moderate, high, and very high (2.0%, 10.2%, 11.5%, 21.2% and 56.2%, respectively). The decision curve analysis verified that the machine learning model is the best clinically valuable in predicting mortality risk.

Conclusion
Using readily available clinical data in the intensive care unit, we built a machine learning-based mortality risk tool with prediction accuracy superior to that of linear regression model and common risk scores. The risk tool may support clinicians in assessing individual patients and making individualized treatment.
Relationship between gene expression patterns from nasopharyngeal swabs and serum biomarkers in patients hospitalized with COVID-19, following treatment with the neutralizing monoclonal antibody bamlanivimab
Authors: Sims Jonathan T. , Poorbaugh Josh , Chang Ching-Yun , Holzer Timothy R. , Zhang Lin , Engle Sarah M. , Beasley Stephanie , Doman Thompson N. , Naughton Lynn , Higgs Richard E. , Kallewaard Nicole , Benschop Robert J. 
Published: March 2022

Abstract
Background
A thorough understanding of a patient’s inflammatory response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is crucial to discerning the associated, underlying immunological processes and to the selection and implementation of treatment strategies. Defining peripheral blood biomarkers relevant to SARS-CoV-2 infection is fundamental to detecting and monitoring this systemic disease. This safety-focused study aims to monitor and characterize the immune response to SARS-CoV-2 infection via analysis of peripheral blood and nasopharyngeal swab samples obtained from patients hospitalized with Coronavirus disease 2019 (COVID-19), in the presence or absence of bamlanivimab treatment.

Methods
23 patients hospitalized with COVID-19 were randomized to receive a single dose of the neutralizing monoclonal antibody, bamlanivimab (700 mg, 2800 mg or 7000 mg) or placebo, at study initiation (Clinical Trial; NCT04411628). Serum samples and nasopharyngeal swabs were collected at multiple time points over 1 month. A Proximity Extension Array was used to detect inflammatory profiles from protein biomarkers in the serum of hospitalized COVID-19 patients relative to age/sex-matched healthy controls. RNA sequencing was performed on nasopharyngeal swabs. A Luminex serology assay and Elecsys® Anti-SARS-CoV-2 immunoassay were used to detect endogenous antibody formation and to monitor seroconversion in each cohort over time. A mixed model for repeated measures approach was used to analyze changes in serology and serum proteins over time.

Results
Levels of IL-6, CXCL10, CXCL11, IFNγ and MCP-3 were > fourfold higher in the serum of patients with COVID-19 versus healthy controls and linked with observations of inflammatory and viral-induced interferon response genes detected in nasopharyngeal swab samples from the same patients. While IgA and IgM titers peaked around 7 days post-dose, IgG titers remained high, even after 28 days. Changes in biomarkers over time were not significantly different between the bamlanivimab and placebo groups.

Conclusions
Similarities observed between nasopharyngeal gene expression patterns and peripheral blood biomarker profiles reveal a connection between the circulation and processes in the nasopharyngeal cavity, reinforcing the potential utility of systemic blood biomarker profiling for therapeutic monitoring of patient response. Serological antibody responses in patients correlated closely with reductions in the COVID-19 inflammatory protein biomarker signature. Bamlanivimab did not affect the biomarker dynamics in this hospitalized patient population.
Is there a trade-off between economy and task goal variability in transfemoral amputee gait?
Authors: Lee I-Chieh , Fylstra Bretta L. , Liu Ming , Lenzi Tommaso , Huang He 
Published: March 2022

Abstract
Background
Energy cost minimization has been widely accepted to regulate gait. Optimization principles have been frequently used to explain how individuals adapt their gait pattern. However, there have been rare attempts to account for the role of variability in this optimization process. Motor redundancy can enable individuals to perform tasks reliably while achieving energy optimization. However, we do not know how the non-goal-equivalent and goal-equivalent variability is regulated. In this study, we investigated how unilateral transfemoral amputees regulate step and stride variability based on the task to achieve energy economy.

Methods
Nine individuals with unilateral transfemoral amputation walked on a treadmill at speeds of 0.6, 0.8, 1.0, 1.2 and 1.4 m/s using their prescribed passive prostheses. We calculated the step-to-step and stride-to-stride variability and applied goal equivalent manifold (GEM) based control to decompose goal-equivalent and non-goal-equivalent manifold. To quantify the energy economy, the energy recovery rate (R) was calculated based on potential energy and kinetic energy. Comparisons were made between GEM variabilities and commonly used standard deviation measurements. A linear regression model was used to investigate the trade-off between R and GEM variabilities.

Results
Our analysis shows greater variability along the goal-equivalent manifold compared to the non-goal-equivalent manifold (p < 0.001). Moreover, our analysis shows lower energy recovery rate for amputee gait compared to nonamputee gait (at least 20% less at faster walking speed). We found a negative relationship between energy recovery rate and non-goal-equivalent variability. Compared to the standard deviation measurements, the variability decomposed using GEM reflected the preferred walking speed and the limitation of the passive prosthetic device.

Conclusion
Individuals with amputation cleverly leverage task redundancy, regulating step and stride variability to the GEM. This result suggests that task redundancy enables unilateral amputees to benefit from motor variability in terms of energy economy. The differences observed between prosthetic step and intact step support the development of prosthetic limbs capable of enhancing positive work during the double support phase and of powered prosthesis controllers that allow for variability along the task space while minimizing variability that interferes with the task goal. This study provides a different perspective on amputee gait analysis and challenges the field to think differently about the role of variability.
Circulation of genotypes of dengue virus serotype 2 in Guangzhou over a period of 20 years
Authors: Jiang Liyun , Liu Yuan , Su Wenzhe , Cao Yimin , Jing Qinlong , Wu Xinwei , Yang Zhicong 
Published: March 2022

Abstract
Background
The dengue epidemic in Guangzhou has imposed a rising burden on society and health infrastructure. Here, we present the genotype data for dengue virus serotype 2 (DENV-2) to improve understanding of this dengue epidemic.

Methods
We sequenced the envelope gene of DENV-2 obtained from patient serum samples and subsequently performed maximum-likelihood phylogenetic analysis using PhyMLv3.1, maximum clade credibility analysis using BEAST v.1.10.4, and selection pressure analysis using Datamonkey 2.0.

Results
The prevalent DENV-2 strains identified in Guangzhou region are related to those in Southeast Asian countries. In particular, the Malaysia/Indian subcontinent genotype is prevailing in Guangzhou with no apparent genotype shift having occurred over the past 20 years. However, episodic positive selection was detected at one site.

Conclusions
Local control of the DENV-2 epidemic in Guangzhou requires effective measures to prevent and monitor imported cases. Moreover, the shift between the Malaysia/Indian subcontinent genotype lineages, which originated at different time points, may account for the rise in DENV-2 cases in Guangzhou. Meanwhile, the low rate of dengue haemorrhagic fever in Guangzhou may be explained by the dominance of the less virulent Malaysia/Indian subcontinent genotype.
Association of serum methionine metabolites with non-alcoholic fatty liver disease: a cross-sectional study
Authors: Tang Yi , Chen Xu , Chen Qian , Xiao Jinghe , Mi Jiaxin , Liu Qiannan , You Yiran , Chen Yuming , Ling Wenhua 
Published: March 2022

Abstract
Background and project
Non-alcoholic fatty liver disease (NAFLD) is viewed as the hepatic manifestation of metabolic syndrome. Methionine metabolites have been linked to metabolic syndrome and its related diseases. Whether serum methionine metabolites levels are associated with NAFLD remains unclear. The study aimed to assess the association between methionine metabolites and NAFLD.

Methods
This cross-sectional study included a total of 2814 individuals aged 40–75 years old. All participants underwent anthropometric measurements, laboratory tests, dietary assessment and abdominal ultrasonography. Multivariable logistic regression analysis was performed to estimate the association of methionine metabolites with NAFLD.

Results
Overall, 1446 with and 1368 without NAFLD were enrolled in this study. Participants with NAFLD had significantly higher serum S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and homocysteine (Hcy) levels, and a lower S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) ratio than those without NAFLD (all P < 0.001). After adjusting multiple confounders, odds ratios (95% confidence interval) for quartile 4 versus quartile 1 of SAH, Hcy and SAM/SAH ratio were 1.65 (1.27–2.14), 1.63 (1.26–2.12) and 0.63 (0.49–0.83), respectively (all P for trend < 0.01). In addition, serum SAH, Hcy levels and SAM/SAH ratio were significantly correlated with the degree of hepatic steatosis (all P for trend < 0.001).

Conclusion
Elevated serum SAH, Hcy levels and lower SAM/SAH ratio may be independently associated with the presence of NAFLD in middle-aged and elder Chinese.
Validation of an MRI-only planning workflow for definitive pelvic radiotherapy
Authors: O’Connor Laura M. , Dowling Jason A. , Choi Jae Hyuk , Martin Jarad , Warren-Forward Helen , Richardson Haylea , Best Leah , Skehan Kate , Kumar Mahesh , Govindarajulu Geetha , Sridharan Swetha , Greer Peter B. 
Published: March 2022

Abstract
Purpose
Previous work on Magnetic Resonance Imaging (MRI) only planning has been applied to limited treatment regions with a focus on male anatomy. This research aimed to validate the use of a hybrid multi-atlas synthetic computed tomography (sCT) generation technique from a MRI, using a female and male atlas, for MRI only radiation therapy treatment planning of rectum, anal canal, cervix and endometrial malignancies.

Patients and methods
Forty patients receiving radiation treatment for a range of pelvic malignancies, were separated into male (n = 20) and female (n = 20) cohorts for the creation of gender specific atlases. A multi-atlas local weighted voting method was used to generate a sCT from a T1-weighted VIBE DIXON MRI sequence. The original treatment plans were copied from the CT scan to the corresponding sCT for dosimetric validation.

Results
The median percentage dose difference between the treatment plan on the CT and sCT at the ICRU reference point for the male cohort was − 0.4% (IQR of 0 to − 0.6), and − 0.3% (IQR of 0 to − 0.6) for the female cohort. The mean gamma agreement for both cohorts was > 99% for criteria of 3%/2 mm and 2%/2 mm. With dose criteria of 1%/1 mm, the pass rate was higher for the male cohort at 96.3% than the female cohort at 93.4%. MRI to sCT anatomical agreement for bone and body delineated contours was assessed, with a resulting Dice score of 0.91 ± 0.2 (mean ± 1 SD) and 0.97 ± 0.0 for the male cohort respectively; and 0.96 ± 0.0 and 0.98 ± 0.0 for the female cohort respectively. The mean absolute error in Hounsfield units (HUs) within the entire body for the male and female cohorts was 59.1 HU ± 7.2 HU and 53.3 HU ± 8.9 HU respectively.

Conclusions
A multi-atlas based method for sCT generation can be applied to a standard T1-weighted MRI sequence for male and female pelvic patients. The implications of this study support MRI only planning being applied more broadly for both male and female pelvic sites.
Trial registration This trial was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) (www.anzctr.org.au) on 04/10/2017. Trial identifier ACTRN12617001406392.
Fast characterization of segmental duplication structure in multiple genome assemblies
Authors: Išerić Hamza , Alkan Can , Hach Faraz , Numanagić Ibrahim 
Published: March 2022

Abstract
Motivation
The increasing availability of high-quality genome assemblies raised interest in the characterization of genomic architecture. Major architectural elements, such as common repeats and segmental duplications (SDs), increase genome plasticity that stimulates further evolution by changing the genomic structure and inventing new genes. Optimal computation of SDs within a genome requires quadratic-time local alignment algorithms that are impractical due to the size of most genomes. Additionally, to perform evolutionary analysis, one needs to characterize SDs in multiple genomes and find relations between those SDs and unique (non-duplicated) segments in other genomes. A naïve approach consisting of multiple sequence alignment would make the optimal solution to this problem even more impractical. Thus there is a need for fast and accurate algorithms to characterize SD structure in multiple genome assemblies to better understand the evolutionary forces that shaped the genomes of today.

Results
Here we introduce a new approach, BISER, to quickly detect SDs in multiple genomes and identify elementary SDs and core duplicons that drive the formation of such SDs. BISER improves earlier tools by (i) scaling the detection of SDs with low homology to multiple genomes while introducing further 7–33$$\times$$
×
speed-ups over the existing tools, and by (ii) characterizing elementary SDs and detecting core duplicons to help trace the evolutionary history of duplications to as far as 300 million years.

Availability and implementation
BISER is implemented in Seq programming language and is publicly available at https://github.com/0xTCG/biser.
Cancer vaccines as promising immuno-therapeutics: platforms and current progress
Authors: Liu Jian , Fu Minyang , Wang Manni , Wan Dandan , Wei Yuquan , Wei Xiawei 
Published: March 2022

AbstractResearch on tumor immunotherapy has made tremendous progress in the past decades, with numerous studies entering the clinical evaluation. The cancer vaccine is considered a promising therapeutic strategy in the immunotherapy of solid tumors. Cancer vaccine stimulates anti-tumor immunity with tumor antigens, which could be delivered in the form of whole cells, peptides, nucleic acids, etc.Ideal cancer vaccines could overcome the immune suppression in tumors and induce both humoral immunity and cellular immunity. In this review, we introduced the working mechanism of cancer vaccines and summarized four platforms for cancer vaccine development. We also highlighted the clinical research progress of the cancer vaccines, especially focusing on their clinical application and therapeutic efficacy, which might hopefully facilitate the future design of the cancer vaccine.
Determinants of SARS-CoV-2 waning immunity in allogeneic hematopoietic stem cell transplant recipients
Authors: Leclerc Mathieu , Redjoul Rabah , Le Bouter Anne , Beckerich Florence , Robin Christine , Parinet Vincent , Pautas Cécile , Menouche Dehbia , Bouledroua Selwa , Roy Lydia , Cabanne Ludovic , Nait-Sidenas Yakout , Fourati Slim , Maury Sébastien 
Published: March 2022

AbstractHematopoietic stem cell transplant (HSCT) recipients are at high-risk for severe COVID-19 and have altered immune responses to vaccination. We sought to evaluate the dynamics of immune response to BNT162b2 mRNA vaccine in HSCT recipients. We systematically proposed vaccination with BNT162b2 to HSCT recipients and gave a third vaccine dose to those showing titers of IgG(S-RBD) below 4160 AU/mL 1 month following the second dose. We then quantified anti-SARS-CoV-2 antibodies dynamics in 133 of these HSCT recipients (88 after two and 45 after three vaccine doses) 6 months after the first vaccine dose. Mean IgG(S-RBD) titer at 6 months was significantly lower than the peak value measured 1 month after a second (p < 0.001) or third (p < 0.01) vaccine dose. IgG(S-RBD) titers at 6 months were strongly correlated to peak values (p < 0.001) and a peak titer above 10,370 AU/mL predicted persistent protection at 6 months. Seventy-two percent (96/133) of patients retained protective antibody levels at 6 months. Immunosuppressive drugs and low lymphocyte counts in peripheral blood correlated with lower IgG(S-RBD) titers at 6 months. Four patients (3%) developed PCR-documented SARS-CoV-2 infection and one died.
Quantitative glycoproteomics analysis identifies novel FUT8 targets and signaling networks critical for breast cancer cell invasiveness
Authors: Tu Cheng-Fen , Li Fu-An , Li Ling-Hui , Yang Ruey-Bing 
Published: March 2022

Abstract
Background
We recently showed that fucosyltransferase 8 (FUT8)-mediated core fucosylation of transforming growth factor-β receptor enhances its signaling and promotes breast cancer invasion and metastasis. However, the complete FUT8 target glycoproteins and their downstream signaling networks critical for breast cancer progression remain largely unknown.

Method
We performed quantitative glycoproteomics with two highly invasive breast cancer cell lines to unravel a comprehensive list of core-fucosylated glycoproteins by comparison to parental wild-type and FUT8-knockout counterpart cells. In addition, ingenuity pathway analysis (IPA) was performed to highlight the most enriched biological functions and signaling pathways mediated by FUT8 targets. Novel FUT8 target glycoproteins with biological interest were functionally studied and validated by using LCA (Lens culinaris agglutinin) blotting and LC–MS/MS (liquid chromatography–tandem mass spectrometry) analysis.

Results
Loss-of-function studies demonstrated that FUT8 knockout suppressed the invasiveness of highly aggressive breast carcinoma cells. Quantitative glycoproteomics identified 140 common target glycoproteins. Ingenuity pathway analysis (IPA) of these target proteins gave a global and novel perspective on signaling networks essential for breast cancer cell migration and invasion. In addition, we showed that core fucosylation of integrin αvβ5 or IL6ST might be crucial for breast cancer cell adhesion to vitronectin or enhanced cellular signaling to interleukin 6 and oncostatin M, two cytokines implicated in the breast cancer epithelial–mesenchymal transition and metastasis.

Conclusions
Our report reveals a comprehensive list of core-fucosylated target proteins and provides novel insights into signaling networks crucial for breast cancer progression. These findings will assist in deciphering the complex molecular mechanisms and developing diagnostic or therapeutic approaches targeting these signaling pathways in breast cancer metastasis.