bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study
Authors: Chevli Parag Anilkumar , Freedman Barry I. , Hsu Fang-Chi , Xu Jianzhao , Rudock Megan E. , Ma Lijun , Parks John S. , Palmer Nicholette D. , Shapiro Michael D. 
Published: December 2021

Abstract
Background
Incidence rates of cardiovascular disease (CVD) are increasing, partly driven by the diabetes epidemic. Novel prediction tools and modifiable treatment targets are needed to enhance risk assessment and management. Plasma metabolite associations with subclinical atherosclerosis were investigated in the Diabetes Heart Study (DHS), a cohort enriched for type 2 diabetes (T2D).

Methods
The analysis included 700 DHS participants, 438 African Americans (AAs), and 262 European Americans (EAs), in whom coronary artery calcium (CAC) was assessed using ECG-gated computed tomography. Plasma metabolomics using liquid chromatography-mass spectrometry identified 853 known metabolites. An ancestry-specific marginal model incorporating generalized estimating equations examined associations between metabolites and CAC (log-transformed (CAC + 1) as outcome measure). Models were adjusted for age, sex, BMI, diabetes duration, date of plasma collection, time between plasma collection and CT exam, low-density lipoprotein cholesterol (LDL-C), and statin use.

Results
At an FDR-corrected p-value < 0.05, 33 metabolites were associated with CAC in AAs and 36 in EAs. The androgenic steroids, fatty acid, phosphatidylcholine, and bile acid metabolism subpathways were associated with CAC in AAs, whereas fatty acid, lysoplasmalogen, and branched-chain amino acid (BCAA) subpathways were associated with CAC in EAs.

Conclusions
Strikingly different metabolic signatures were associated with subclinical coronary atherosclerosis in AA and EA DHS participants.
Rapid detection of a novel B1-β-lactamase gene, blaAFM-1 using a loop-mediated isothermal amplification (LAMP) assay
Authors: Qin Yingcheng , Duan Xiaonv , Peng Yuan , Rui Yongyu 
Published: December 2021

Abstract
Background
BlaAFM-1 (GenBank Accession No. 143105.1) is a new B1 subclass metallo-β-lactamase gene discovered by our group, and isolated from an Alcaligenes faecalis plasmid that renders carbapenem antibiotics ineffective. In this study, we generated a fast and reliable assay for blaAFM-1 detection.

Methods
We designed optimum loop-mediated isothermal amplification (LAMP) primers and constructed a recombinant plasmid AFM-1 to specifically detect blaAFM-1. Optimal LAMP primers were used to assess sensitivity of the recombinant plasmid AFM-1 and blaAFM-1-supplemented samples (simulated sputum and simulated feces). Fifty two samples, without blaAFM-1, were used to assess LAMP real-time assay specificity; these samples were verified by conventional PCR and sequencing for the absence of blaAFM-1. Three hundred clinical Gram-negative carbapenem-resistant strains were tested by LAMP assay for strains carrying blaAFM-1, which were confirmed by conventional PCR and Sanger sequencing. We calculated the sensitivity and its 95% confidence interval (95% CI), specificity and its 95% CI, and predictive values of the LAMP assay and conventional PCR/sequencing by investigating positive and negative clinical strains.

Results
The lowest limit of detection for the recombinant plasmid AFM-1 and blaAFM-1-supplemented samples (in both simulated sputum and simulated feces) was 101 copies/reaction. All amplification curves of the 52 blaAFM-1-free bacteria strains were negative, suggesting the LAMP assay had excellent specificity for detecting blaAFM-1. Among the 300 clinical strains, eight were positive for blaAFM-1 using LAMP. These LAMP results were consistent with conventional PCR and Sanger sequencing data. As with conventional PCR/sequencing, the LAMP method exhibits 100% sensitivity (95% CI 59.8–100%) and 100% specificity (95% CI 98.4–100%) for blaAFM-1 detection. The LAMP assay is also time-efficient (1 h) for blaAFM-1 detection.

Conclusions
We established a new LAMP assay with high sensitivity and specificity to detect the novel B1-β-lactamase gene, blaAFM-1.
The hazardous (mis)perception of Self-estimated Alcohol intoxication and Fitness to drivE—an avoidable health risk: the SAFE randomised trial
Authors: Köchling Jöran , Geis Berit , Chao Cho-Ming , Dieks Jana-K. , Wirth Stefan , Hensel Kai O. 
Published: December 2021

Abstract
Background
Worldwide, alcohol-related road traffic accidents represent a major avoidable health risk. The aim of this study was to evaluate the accuracy of self-estimating the degree of acute alcohol intoxication regarding the legal driving limit, and to identify risk factors for misjudgement.

Methods
In this prospective randomised controlled crossover trial, 90 social drinkers (mean age 23.9 ± 3.5 years, 50% female) consumed either beer or wine. Study group subjects were made aware when exceeding the legal driving limit (BrAC = 0.05%). Controls received no information about their BrAC. For crossover, beer or wine were consumed in the opposite order.

Results
39–53% of all participants exceeded the legal driving limit whilst under the impression to be still permitted to drive. Self-estimation was significantly more accurate on study day 2 (p = 0.009). Increasing BrAC positively correlated with self-estimation inaccuracy, which was reproducible during crossover. Multiple regression analysis revealed fast drinking and higher alcohol levels as independent risk factors for inaccurate self-estimation.

Conclusions
Social drinkers are commonly unaware of exceeding the legal driving limit when consuming alcohol. Self-estimating alcohol intoxication can be improved through awareness. Dedicated awareness programs, social media campaigns and government advice communications should be utilised to address this avoidable hazard.
Trial registration The trial was registered prospectively at the Witten/Herdecke University Ethics Committee (trial registration number 140/2016 on 04/11/2016) and at the DRKS—German Clinical Trials Register (trial registration number DRKS00015285 on 08/22/2018—Retrospectively registered). Trial protocol can be accessed online.
LINC00491 promotes cell growth and metastasis through miR-324-5p/ROCK1 in liver cancer
Authors: Wang Wei , Yang Tao , Li Dongsheng , Huang Yinpeng , Bai Guang , Li Qing 
Published: December 2021

Abstract
Background
LINC00491 was involved in some tumors development, but its function in liver cancer has not been reported. This study aimed to investigate LINC00491 expression and function in liver cancer progression.

Methods
Sixty liver cancer cases were enrolled. LINC00491, miR-324-5p and rho-associated kinase 1 (ROCK1) expression in liver cancer patients and cells were detected by quantitative reverse transcription-polymerase chain reaction and Western blot. HUH-7 and SK-Hep-1 cells were transfected to modulate LINC00491, miR-324-5p and ROCK1 expression. Cell counting kit-8 assay, colony formation assay, wound healing assay, Transwell experiment, Tunel assay and flow cytometry were performed to detected HUH-7 and SK-Hep-1 cells proliferation, migration, invasion, apoptosis and cell cycle. Biotin-RNA pull-down assay and Dual-Luciferase Reporter Assay was performed to detect the binding among LINC00491, miR-324-5p and ROCK1. Xenograft tumor and lung metastasis was performed using nude mice. Xenograft tumor and lung tissues of mice were experienced immunohistochemistry and hematoxylin–eosin staining.

Results
LINC00491 was highly expressed in liver cancer cases, associating with poor prognosis. si-LINC00491 inhibited proliferation, colony formation, invasion, migration, and induced cell cycle G1 arrest and apoptosis in HUH-7 and SK-Hep-1 cells. LINC00491 overexpression showed opposite effects. LINC00491 promoted ROCK1 expression by reducing miR-324-5p. miR-324-5p up-regulation or ROCK1 knockdown reversed LINC00491 promotion on liver SK-Hep-1 cells malignant phenotype. LINC00491 facilitated xenograft tumor growth and lung metastasis in mice.

Conclusion
LINC00491 was highly expressed in liver cancer patients, associating with poor prognosis. LINC00491 facilitated liver cancer progression by sponging miR-324-5p/ROCK1. LINC00491 might be a potential treatment target of liver cancer.
Hepatitis B virus polymerase-specific T cell epitopes shift in a mouse model of chronic infection
Authors: Hasanpourghadi Mohadeseh , Novikov Mikhail , Newman Dakota , Xiang ZhiQuan , Zhou Xiang Yang , Magowan Colin , Ertl Hildegund C. J. 
Published: December 2021

AbstractBackgroundChronic hepatitis B virus (HBV) infection (CHB) is a significant public health problem that could benefit from treatment with immunomodulators. Here we describe a set of therapeutic HBV vaccines that target the internal viral proteins.MethodsVaccines are delivered by chimpanzee adenovirus vectors (AdC) of serotype 6 (AdC6) and 7 (AdC7) used in prime only or prime-boost regimens. The HBV antigens are fused into an early T cell checkpoint inhibitor, herpes simplex virus (HSV) glycoprotein D (gD), which enhances and broadens vaccine-induced cluster of differentiation (CD8)+T cell responses.ResultsOur results show that the vaccines are immunogenic in mice. They induce potent CD8+T cell responses that recognize multiple epitopes. CD8+T cell responses increase after a boost, although the breadth remains similar. In mice, which carry high sustained loads of HBV particles due to a hepatic infection with an adeno-associated virus (AAV)8 vector expressing the 1.3HBV genome, CD8+T cell responses to the vaccines are attenuated with a marked shift in the CD8+T cells’ epitope recognition profile.ConclusionsOur data show that in different stains of mice including those that carry a human major histocompatibility complex (MHC) class I antigen HBV vaccines adjuvanted with a checkpoint inhibitor induce potent and broad HBV-specific CD8+T cell responses and lower but still detectable CD4+T cell responses. CD8+T cell responses are reduced and their epitope specificity changes in mice that are chronically exposed to HBV antigens. Implications for the design of therapeutic HBV vaccines are discussed.
Effectiveness of a fortified drink in improving B vitamin biomarkers in older adults: a controlled intervention trial
Authors: Heffernan Maria , Doherty Leanne C. , Hack Mendes Roberta , Clarke Michelle , Hodge Stephanie , Clements Michelle , McAnena Liadhan , Rivelsrud Mari , Ward Mary , Strain J. J. , McNulty Helene , Brennan Lorraine 
Published: December 2021

Abstract
Background
Older adults are reported to have sub-optimal B vitamin status; targeted food-based solutions may help to address this. The objectives of the OptiAge food intervention study were to develop and investigate the effectiveness of a B vitamin-fortified drink in improving B vitamin biomarkers in older Irish adults with a primary outcome of change in the B vitamin biomarker status.

Methods
A double-blinded randomised controlled trial was performed in parallel at University College Dublin and Ulster University. Participants aged > 50 years were recruited following screening for exclusion criteria (i.e. taking medications known to interfere with B vitamin metabolism, supplements containing B vitamins, consuming > 4 portions of B vitamin-fortified foods per week or diagnosed with gastrointestinal, liver or pulmonary disease). Recruited participants meeting the inclusion criteria were randomised (by sex and study centre) to receive daily for 16 weeks either B vitamin-fortified or placebo drinks as developed by Smartfish, Norway. Each B vitamin-fortified drink (200 ml) contained 200 µg folic acid, 10 µg vitamin B12, 10 mg vitamin B6 and 5 mg riboflavin, while the placebo was an identical, isocaloric formulation without added B vitamins. Fasting blood samples were collected pre- and post-intervention which were used to measure the primary outcome of change in B vitamin biomarker levels.

Results
A total of 95 participants were randomised, of which 81 commenced the trial. Of these, 70 completed (37 in the active and 33 in the placebo groups). Intention to treat (ITT) analysis of the B vitamins demonstrated a significant improvement in all B vitamin biomarkers in the active compared to placebo groups: p < 0.01 for each of serum folate, serum vitamin B12 and plasma pyridoxal 5′-phosphate (vitamin B6) and the functional riboflavin biomarker, erythrocyte glutathione reductase activation coefficient (EGRac). Correspondingly, a significant lowering of serum homocysteine from 11.9 (10.3–15.1) µmol/L to 10.6 (9.4–13.0) µmol/L was observed in response to the active treatment (P < 0.001). Similar results were seen in a per-protocol analysis.

Conclusions
The results demonstrate that a B vitamin-fortified drink was effective in optimising B vitamin status, making this a useful intervention option to improve B vitamin status in older adults.
Trial registration ISRCTN, ISRCTN61709781—Retrospectively registered, https://www.isrctn.com/ISRCTN61709781
Quantitative analysis of macroscopic solute transport in the murine brain
Authors: Ray Lori A. , Pike Martin , Simon Matthew , Iliff Jeffrey J. , Heys Jeffrey J. 
Published: December 2021

Abstract
Background
Understanding molecular transport in the brain is critical to care and prevention of neurological disease and injury. A key question is whether transport occurs primarily by diffusion, or also by convection or dispersion. Dynamic contrast-enhanced (DCE-MRI) experiments have long reported solute transport in the brain that appears to be faster than diffusion alone, but this transport rate has not been quantified to a physically relevant value that can be compared to known diffusive rates of tracers.

Methods
In this work, DCE-MRI experimental data is analyzed using subject-specific finite-element models to quantify transport in different anatomical regions across the whole mouse brain. The set of regional effective diffusivities ($$D_{eff}$$

D

eff

), a transport parameter combining all mechanisms of transport, that best represent the experimental data are determined and compared to apparent diffusivity ($$D_{app}$$

D

app

), the known rate of diffusion through brain tissue, to draw conclusions about dominant transport mechanisms in each region.

Results
In the perivascular regions of major arteries, $$D_{eff}$$

D

eff

for gadoteridol (550 Da) was over 10,000 times greater than $$D_{app}$$

D

app

. In the brain tissue, constituting interstitial space and the perivascular space of smaller blood vessels, $$D_{eff}$$

D

eff

was 10–25 times greater than $$D_{app}$$

D

app

.

Conclusions
The analysis concludes that convection is present throughout the brain. Convection is dominant in the perivascular space of major surface and branching arteries (Pe > 1000) and significant to large molecules (> 1 kDa) in the combined interstitial space and perivascular space of smaller vessels (not resolved by DCE-MRI). Importantly, this work supports perivascular convection along penetrating blood vessels.
Phenotyping seedlings for selection of root system architecture in alfalfa (Medicago sativa L.)
Authors: Bucciarelli Bruna , Xu Zhanyou , Ao Samadangla , Cao Yuanyuan , Monteros Maria J. , Topp Christopher N. , Samac Deborah A. 
Published: December 2021

Abstract
Background
The root system architecture (RSA) of alfalfa (Medicago sativa L.) affects biomass production by influencing water and nutrient uptake, including nitrogen fixation. Further, roots are important for storing carbohydrates that are needed for regrowth in spring and after each harvest. Previous selection for a greater number of branched and fibrous roots significantly increased alfalfa biomass yield. However, phenotyping root systems of mature alfalfa plant is labor-intensive, time-consuming, and subject to environmental variability and human error. High-throughput and detailed phenotyping methods are needed to accelerate the development of alfalfa germplasm with distinct RSAs adapted to specific environmental conditions and for enhancing productivity in elite germplasm. In this study methods were developed for phenotyping 14-day-old alfalfa seedlings to identify measurable root traits that are highly heritable and can differentiate plants with either a branched or a tap rooted phenotype. Plants were grown in a soil-free mixture under controlled conditions, then the root systems were imaged with a flatbed scanner and measured using WinRhizo software.

Results
The branched root plants had a significantly greater number of tertiary roots and significantly longer tertiary roots relative to the tap rooted plants. Additionally, the branch rooted population had significantly more secondary roots > 2.5 cm relative to the tap rooted population. These two parameters distinguishing phenotypes were confirmed using two machine learning algorithms, Random Forest and Gradient Boosting Machines. Plants selected as seedlings for the branch rooted or tap rooted phenotypes were used in crossing blocks that resulted in a genetic gain of 10%, consistent with the previous selection strategy that utilized manual root scoring to phenotype 22-week-old-plants. Heritability analysis of various root architecture parameters from selected seedlings showed tertiary root length and number are highly heritable with values of 0.74 and 0.79, respectively.

Conclusions
The results show that seedling root phenotyping is a reliable tool that can be used for alfalfa germplasm selection and breeding. Phenotypic selection of RSA in seedlings reduced time for selection by 20 weeks, significantly accelerating the breeding cycle.
Clinical characteristics and risk factors associated with mortality in patients with severe community-acquired pneumonia and type 2 diabetes mellitus
Authors: Huang Dong , He Dingxiu , Gong Linjing , Wang Wen , Yang Lei , Zhang Zhongwei , Shi Yujun , Liang Zongan 
Published: December 2021

Abstract
Background
The present study was performed to investigate the impacts of type 2 diabetes mellitus (T2DM) on severe community-acquired pneumonia (SCAP) and to develop a novel prediction model for mortality in SCAP patients with T2DM.

Methods
This was a retrospective observational study conducted in consecutive adult patients with SCAP admitted to the intensive care unit (ICU) of West China Hospital, Sichuan University, China, between September 2011 and September 2019. The primary outcome was hospital mortality. A propensity score matching (PSM) analysis model with a 1:2 ratio was used for the comparisons of clinical characteristics and outcomes between T2DM and nondiabetic patients. The independent risk factors were identified via univariate and then multivariable logistic regression analysis and were then used to establish a nomogram.

Results
In total, 1262 SCAP patients with T2DM and 2524 matched patients without T2DM were included after PSM. Patients with T2DM had longer ICU length of stay (LOS) (13 vs. 12 days, P = 0.016) and higher 14-day mortality (15% vs. 10.8%, P < 0.001), 30-day mortality (25.7% vs. 22.7%, P = 0.046), ICU mortality (30.8% vs. 26.5%, P = 0.005), and hospital mortality (35.2% vs. 31.0%, P = 0.009) than those without T2DM. In SCAP patients with T2DM, the independent risk factors for hospital mortality were increased numbers of comorbidities and diabetes-related complications; elevated C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), brain natriuretic peptide (BNP) and blood lactate; as well as decreased blood pressure on admission. The nomogram had a C index of 0.907 (95% CI: 0.888, 0.927) in the training set and 0.873 (95% CI: 0.836, 0.911) in the testing set, which was superior to the pneumonia severity index (PSI, AUC: 0.809, 95% CI: 0.785, 0.833). The calibration curve and decision curve analysis (DCA) also demonstrated its accuracy and applicability.

Conclusions
SCAP patients with T2DM had worse clinical outcomes than nondiabetic patients. The nomogram has good predictive performance for hospital mortality and might be generally applied after more external validations.
Autologous full-thickness skin graft as reinforcement in parastomal hernia repair: a randomised controlled trial
Authors: Holmdahl Viktor , Gunnarsson Ulf , Strigård Karin 
Published: December 2021

Abstract
Background
Parastomal hernia is a common complication of an enterostomy and can have a significant impact on health-related quality of life. Currently used methods of repair have high recurrence rates and considerable risk for complications. We have developed a new technique for parastomal hernia repair that uses full-thickness skin graft as reinforcement.

Methods
This study protocol describes a multicentre randomised controlled trial on parastomal hernia repair comparing a new full-thickness skin graft technique with conventional synthetic composite mesh as reinforcement of the abdominal wall. Patients with a symptomatic parastomal hernia will be included and followed up at 3, 12 and 36 months, with surgical complication as the primary outcome. Secondary outcomes will be recurrence rate and health-related quality of life assessed with VHPQ, EORTC C30 and CR29. Tissue biology and collagen metabolism will be investigated pre- and postoperatively using biopsies of the abdominal wall fascia and blood samples.

Discussion
Parastomal hernia constitutes a major clinical problem where the prospects of a good result after hernia repair are presently poor. This new method of repair with full-thickness skin grafting could be a new alternative in our surgical toolbox, but before then, it must be evaluated properly.

Trial registration
ClinicalTrials.gov NCT03667287. Registered on September 12, 2018
Catalase deficiency facilitates the shuttling of free fatty acid to brown adipose tissue through lipolysis mediated by ROS during sustained fasting
Authors: Dutta Raghbendra Kumar , Lee Joon No , Maharjan Yunash , Park Channy , Choe Seong-Kyu , Ho Ye-Shih , Park Raekil 
Published: December 2021

Abstract
Background
Fatty acids (FA) derived from adipose tissue and liver serve as the main fuel in thermogenesis of brown adipose tissue (BAT). Catalase, a peroxisomal enzyme, plays an important role in maintaining intracellular redox homeostasis by decomposing hydrogen peroxide to either water or oxygen that oxidize and provide fuel for cellular metabolism. Although the antioxidant enzymatic activity of catalase is well known, its role in the metabolism and maintenance of energy homeostasis has not yet been revealed. The present study investigated the role of catalase in lipid metabolism and thermogenesis during nutrient deprivation in catalase-knockout (KO) mice.

Results
We found that hepatic triglyceride accumulation in KO mice decreased during sustained fasting due to lipolysis through reactive oxygen species (ROS) generation in adipocytes. Furthermore, the free FA released from lipolysis were shuttled to BAT through the activation of CD36 and catabolized by lipoprotein lipase in KO mice during sustained fasting. Although the exact mechanism for the activation of the FA receptor enzyme, CD36 in BAT is still unclear, we found that ROS generation in adipocytes mediated the shuttling of FA to BAT.

Conclusions
Taken together, our findings uncover the novel role of catalase in lipid metabolism and thermogenesis in BAT, which may be useful in understanding metabolic dysfunction.

Graphical Abstract