bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normal fasting triglyceride levels and incident type 2 diabetes in the general population
Authors: Szili-Torok Tamas , Bakker Stephan J. L. , Tietge Uwe J. F. 
Published: June 2022

Abstract
Background
Type 2 diabetes is increasing worldwide. Traditionally, only hypertriglyceridemia is considered a risk factor. We investigated whether also normal triglycerides prospectively associate with incident type 2 diabetes in healthy subjects.

Methods
Incident type 2 diabetes was determined in healthy individuals with normal triglyceride levels from a prospective longitudinal cohort study (PREVEND, n = 2085, 11.4-year median follow-up).

Results
Type 2 diabetes incidence was 3.8%. In linear regression analysis baseline insulin, HOMA-IR, total cholesterol, HDL cholesterol, eGFR, systolic blood pressure (all p < 0.001), glucose, age and creatinine (all p < 0.01) independently associated with triglycerides within the normal range, comparable to what would be expected from associations with increased triglycerides. In Kaplan-Meier analysis sex-stratified tertiles of normal triglycerides prospectively associated with de novo type 2 diabetes (p < 0.001). Cox regression confirmed a significant prospective association independent of HOMA-IR [HR (95% CI), 1.39 (1.12, 1.74), p = 0.002] and several other recognized risk factors.

Conclusions
Even in healthy subjects without metabolic syndrome increasing triglyceride levels within the normal range confer a continuous increase in type 2 diabetes incidence. These data indicate that virtually everyone could potentially benefit from triglyceride lowering, further encouraging implementation of lifestyle changes in the general population.
PhoP- and GlnR-mediated regulation of metK transcription and its impact upon S-adenosyl-methionine biosynthesis in Saccharopolyspora erythraea
Authors: Pei Jin-Feng , Li Yu-Xin , Tang Hao , Wei Wenping , Ye Bang-Ce 
Published: June 2022

Abstract
Background
Erythromycin A (Er A) has a broad antibacterial effect and is a source of erythromycin derivatives. Methylation of erythromycin C (Er C), catalyzed by S-adenosyl-methionine (SAM)-dependent O-methyltransferase EryG, is the key final step in Er A biosynthesis. Er A biosynthesis, including EryG production, is regulated by the phosphate response factor PhoP and the nitrogen response factor GlnR. However, the regulatory effect of these proteins upon S-adenosyl-methionine synthetase (MetK) production is unknown.

Results
In this study, we used bioinformatics approaches to identify metK (SACE_3900), which codes for S-adenosyl-methionine synthetase (MetK). Electrophoretic mobility shift assays (EMSAs) revealed that PhoP and GlnR directly interact with the promoter of metK, and quantitative PCR (RT-qPCR) confirmed that each protein positively regulated metK transcription. Moreover, intracellular SAM was increased upon overexpression of either phoP or glnR under phosphate or nitrogen limited conditions, respectively. Finally, both the production of Er A and the transformation ratio from Er C to Er A increased upon phoP overexpression, but surprisingly, not upon glnR overexpression.

Conclusions
Manipulating the phosphate and nitrogen response factors, PhoP and GlnR provides a novel strategy for increasing the yield of SAM and the production of Er A in Saccharopolyspora erythraea .
Towards synthetic PETtrophy: Engineering Pseudomonas putida for concurrent polyethylene terephthalate (PET) monomer metabolism and PET hydrolase expression
Authors: Brandenberg Oliver F. , Schubert Olga T. , Kruglyak Leonid 
Published: June 2022

Abstract
Background
Biocatalysis offers a promising path for plastic waste management and valorization, especially for hydrolysable plastics such as polyethylene terephthalate (PET). Microbial whole-cell biocatalysts for simultaneous PET degradation and growth on PET monomers would offer a one-step solution toward PET recycling or upcycling. We set out to engineer the industry-proven bacterium Pseudomonas putida for (i) metabolism of PET monomers as sole carbon sources, and (ii) efficient extracellular expression of PET hydrolases. We pursued this approach for both PET and the related polyester polybutylene adipate co-terephthalate (PBAT), aiming to learn about the determinants and potential applications of bacterial polyester-degrading biocatalysts.

Results
P. putida was engineered to metabolize the PET and PBAT monomer terephthalic acid (TA) through genomic integration of four tphII operon genes from Comamonas sp. E6. Efficient cellular TA uptake was enabled by a point mutation in the native P. putida membrane transporter MhpT. Metabolism of the PET and PBAT monomers ethylene glycol and 1,4-butanediol was achieved through adaptive laboratory evolution. We then used fast design-build-test-learn cycles to engineer extracellular PET hydrolase expression, including tests of (i) the three PET hydrolases LCC, HiC, and IsPETase; (ii) genomic versus plasmid-based expression, using expression plasmids with high, medium, and low cellular copy number; (iii) three different promoter systems; (iv) three membrane anchor proteins for PET hydrolase cell surface display; and (v) a 30-mer signal peptide library for PET hydrolase secretion. PET hydrolase surface display and secretion was successfully engineered but often resulted in host cell fitness costs, which could be mitigated by promoter choice and altering construct copy number. Plastic biodegradation assays with the best PET hydrolase expression constructs genomically integrated into our monomer-metabolizing P. putida strains resulted in various degrees of plastic depolymerization, although self-sustaining bacterial growth remained elusive.

Conclusion
Our results show that balancing extracellular PET hydrolase expression with cellular fitness under nutrient-limiting conditions is a challenge. The precise knowledge of such bottlenecks, together with the vast array of PET hydrolase expression tools generated and tested here, may serve as a baseline for future efforts to engineer P. putida or other bacterial hosts towards becoming efficient whole-cell polyester-degrading biocatalysts.
Oncogenic functions and clinical significances of DCLK1 isoforms in colorectal cancer: a systematic review and meta-analysis
Authors: Kalantari Elham , Razmi Mahdieh , Tajik Fatemeh , Asadi-Lari Mohsen , Ghods Roya , Madjd Zahra 
Published: June 2022

Abstract
Background
The oncogenic role of doublecortin-like kinase 1 (DCLK1) as a putative cancer stem cell (CSC) marker has been clarified in colorectal cancer (CRC). Isoform-specific functions of DCLK1 have shed new light on different functions of DCLK1 short (DCLK1-S) and DCLK1 long (DCLK1-L) isoforms in tumor initiation, growth, and metastasis. Therefore, the current systematic review and meta-analysis aimed to review the available in vitro, in vivo, and clinical evidence on the oncogenic roles and clinical significance of DCLK1 isoforms in colorectal cancer.

Methods
The literature databases of PubMed, Scopus, ISI Web of Science, and Embase were searched to identify eligible articles. The description characteristics of in vitro and pre-clinical studies were extracted from identified reports. In addition, hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were recorded to determine the relationships between DCLK1-L and DCLK1-S expression and prognostic outcomes in patients with CRC.

Results
Both in vitro and in vivo evidence have emphasized the potential oncogenic functions of DCLK1 in tumor initiation, self-renewal ability, tumor invasion, epithelial-mesenchymal transition (EMT), and metastasis. However, the anti-DCLK1 antibodies generally utilized in these studies could detect sequence homology epitopes of both isoforms. Recent limited isoform-specific evidence has strongly supported the significant positive expression and rather oncogenic efficacy of DCLK1-S in tumorigenesis, EMT, and invasion compared with DCLK1-L in human CRC cell lines. Our meta-analysis findings of limited clinical studies indicated that only overexpression of DCLK1-S is associated with worse overall survival (OS) (HR = 7.930, 95% CI 2.252–27.924, p = 0.001). Increased expression of both DCLK1-S (HR = 1.610, 95% CI 1.020–2.541, p = 0.041) and DCLK1-L (HR = 5.890, 95% CI 1.219–28.453, p = 0.027) isoforms was closely associated with worse DSS/CSS in CRC patients. Furthermore, the high expression of DCLK1-S was found to be associated with poor DFS/RFS/PFS (HR = 1.913, 95% CI 1.230–2.973, p = 0.004).

Conclusions
The current findings strongly supported that the DCLK1-S isoform may play a crucial role in the invasion, aggressive tumor behavior, and worsened survival outcomes of CRC patients. However, further critical investigations related to the potential preclinical and clinical utilities of DCLK1-S as a specific CRC-CSC marker are warranted.
Minimum variance beamforming combined with covariance matrix-based adaptive weighting for medical ultrasound imaging
Authors: Wang Yuanguo , Wang Yadan , Liu Mingzhou , Lan Zhengfeng , Zheng Chichao , Peng Hu 
Published: June 2022

Abstract
Background
The minimum variance (MV) beamformer can significantly improve the image resolution in ultrasound imaging, but it has limited performance in noise reduction. We recently proposed the covariance matrix-based statistical beamforming (CMSB) for medical ultrasound imaging to reduce sidelobes and incoherent clutter.

Methods
In this paper, we aim to improve the imaging performance of the MV beamformer by introducing a new pixel-based adaptive weighting approach based on CMSB, which is named as covariance matrix-based adaptive weighting (CMSAW). The proposed CMSAW estimates the mean-to-standard-deviation ratio (MSR) of a modified covariance matrix reconstructed by adaptive spatial smoothing, rotary averaging, and diagonal reducing. Moreover, adaptive diagonal reducing based on the aperture coherence is introduced in CMSAW to enhance the performance in speckle preservation.

Results
The proposed CMSAW-weighted MV (CMSAW-MV) was validated through simulation, phantom experiments, and in vivo studies. The phantom experimental results show that CMSAW-MV obtains resolution improvement of 21.3% and simultaneously achieves average improvements of 96.4% and 71.8% in average contrast and generalized contrast-to-noise ratio (gCNR) for anechoic cyst, respectively, compared with MV. in vivo studies indicate that CMSAW-MV improves the noise reduction performance of MV beamformer.

Conclusion
Simulation, experimental, and in vivo results all show that CMSAW-MV can improve resolution and suppress sidelobes and incoherent clutter and noise. These results demonstrate the effectiveness of CMSAW in improving the imaging performance of MV beamformer. Moreover, the proposed CMSAW with a computational complexity of $$O(N^2)$$

O
(

N
2

)

has the potential to be implemented in real time using the graphics processing unit.
Barriers to COVID-19 vaccination among older adults in Mexico City
Authors: Gaitán-Rossi Pablo , Mendez-Rosenzweig Miranda , García-Alberto Erika , Vilar-Compte Mireya 
Published: June 2022

AbstractVaccines are effective to reduce COVID-19 related outcomes, but universal vaccination campaigns can reveal within-country access inequities. Mexico City has had high rates of COVID-19 related morbidity and mortality and a population survey warned that vaccine acceptance was lowest in older adults. Since February 2021, Mexico started a universal and free vaccination campaign prioritizing older adults. By April 17, every older adult in Mexico City had been eligible to receive the first dose. A week later, we conducted a telephone survey representative of older adults residing in Mexico City (n = 503). We asked if they received their first dose and, if they haven’t, we followed-up with an open question to register their reasons. In addition to sociodemographic characteristics and food insecurity, we also inquired about vaccine hesitancy, health concerns related to COVID-19, self-rated health, comorbidities, frailty, and depression. The objective of the study was to identify the main barriers to receive the first dose of the vaccine. We estimated descriptive statistics and logistic regression models. Results show that 7.6% of older adults in Mexico City did not receive their first dose. Barriers for not receiving it were vaccine hesitancy (60.4%), not having COVID-19 health concerns (46.4%), poor self-rated health (46.7%), a previous diagnosis of depression (35.7%), low socioeconomic status (65.4%), and household food insecurity (59.8%). Responses to the open question clustered in four themes: misinformation about the process (30%), distrust of the vaccine (24%), personal health problems (24%), and difficulties to get an appointment (22%). Logistic regression models adjusted for vaccine hesitancy and revealed two distinct reasons for not having their first dose: 1) vaccine hesitancy and misinformation on COVID-19, and 2) household food insecurity. Reaching these two groups requires active and differentiated public-health measures; the first with additional information from trusted sources, and the second by facilitating vaccination in neighborhoods with high levels of food insecurity and informal labor, where missing a day’s work is a strong disincentive. Vaccination campaigns need an equity lens to reach universal coverage; ensuring full access demands thorough and carefully tailored new interventions.
Pleural mesothelioma risk by industry and occupation: results from the Multicentre Italian Study on the Etiology of Mesothelioma (MISEM)
Authors: Migliore Enrica , Consonni Dario , Peters Susan , Vermeulen Roel C. H. , Kromhout Hans , Baldassarre Antonio , Cavone Domenica , Chellini Elisabetta , Magnani Corrado , Mensi Carolina , Merler Enzo , Musti Marina , Marinaccio Alessandro , Mirabelli Dario 
Published: June 2022

Abstract
Background
The Italian mesothelioma registry (ReNaM) estimates mesothelioma incidence and addresses its etiology by assessing cases’ exposures but cannot provide relative risk estimates.

Objectives
i) To estimate pleural mesothelioma relative risk by industry and occupation and by ReNaM categories of asbestos exposure; and ii) to provide quantitative estimates of the exposure–response relationship.

Methods
A population-based mesothelioma case–control study was conducted in 2012–2014 in five Italian regions. Cases and age and gender frequency-matched controls were interviewed using a standard ReNaM questionnaire. Experts coded work histories according to international standard classifications of industries/occupations and assigned asbestos exposure according to ReNaM categories. Job codes were further linked to SYN-JEM, a quantitative job-exposure matrix. Cumulative exposure (CE, f/mL-years) was computed by summing individual exposures over lifetime work history. Unconditional logistic regression analyses adjusted by gender, centre and age were fitted to calculate odds ratios (OR) and 95% confidence intervals (CI).

Results
Among men we observed increased risks of mesothelioma in many industries and associated occupations, including: asbestos-cement (OR = 3.43), manufacture of railroad equipment (OR = 8.07), shipbuilding and repairing (OR = 2.34), iron and steel mills (OR = 2.15), and construction (OR = 1.94). ORs by ReNaM exposure categories were as follows: definite/probable occupational exposure (OR = 15.8, men; OR = 8.80, women), possible occupational (OR = 2.82, men; OR = 3.70, women), sharing home with an exposed worker (OR = 2.55, men; OR = 10.3, women), residential (OR = 2.14, men; OR = 3.24, women). Based on SYN-JEM, mesothelioma risk increased by almost 30% per f/mL-year (OR = 1.28, CI 1.16–1.42).

Conclusions
Out study involved five regions with historically different types and levels of industrial development, encompassing one third of the Italian population and half of Italian mesothelioma cases. As expected, we found increased pleural mesothelioma risk in the asbestos industry and in trades with large consumption of asbestos materials. Clear associations were found using both qualitative (ReNaM classifications) and quantitative estimates (using SYN-JEM) of past asbestos exposure, with clear evidence of an exposure–response relationship.
Deviations from typical paths: a novel approach to working with GPS data in the behavioral sciences
Authors: Nielsen Karen E. , Mejía Shannon T. , Gonzalez Richard 
Published: June 2022

Abstract
Background
Behavioral science researchers are increasingly collecting detailed location data such as second-by-second GPS tracking on participants due to increased ease and affordability. While intraindividual variability has been discussed in the travel literature for decades, traditional methods designed for studying individual differences in central tendencies limit the extent to which novel questions about variability in lived experiences can be answered. Thus, new methods of quantifying behavior that focus on intraindividual variability are needed to address the context in which the behavior occurs and the location tracking data from which behavior is derived.

Methods
We propose deviations from typical paths as a data processing technique to separate individual-level typical travel behavior from a location tracking data set in order to highlight atypical travel behavior as an outcome measure.

Results
A simulated data example shows how the method works to produce deviation measures from a location dataset. Analysis of these deviations offers additional insights compared to traditional measures of maximum daily distance from home.

Conclusions
This process can be integrated into larger research questions to explore predictors of atypical behavior and potential mechanisms of behavior change.
Recent advances in pain management based on nanoparticle technologies
Authors: Babaie Soraya , Taghvimi Arezou , Hong Joo-Hyun , Hamishehkar Hamed , An Seongpil , Kim Ki Hyun 
Published: June 2022

Abstract
Background
Pain is a vital sense that indicates the risk of injury at a particular body part. Successful control of pain is the principal aspect in medical treatment. In recent years, the advances of nanotechnology in pain management have been remarkable. In this review, we focus on literature and published data that reveal various applications of nanotechnology in acute and chronic pain management.

Methods
The presented content is based on information collected through pain management publications (227 articles up to April 2021) provided by Web of Science, PubMed, Scopus and Google Scholar services.

Results
A comprehensive study of the articles revealed that nanotechnology-based drug delivery has provided acceptable results in pain control, limiting the side effects and increasing the efficacy of analgesic drugs. Besides the ability of nanotechnology to deliver drugs, sophisticated nanosystems have been designed to enhance imaging and diagnostics, which help in rapid diagnosis of diseases and have a significant impact on controlling pain. Furthermore, with the development of various tools, nanotechnology can accurately measure pain and use these measurements to display the efficiency of different interventions.

Conclusions
Nanotechnology has started a new era in the pain management and many promising results have been achieved in this regard. Nevertheless, there is still no substantial and adequate act of nanotechnology in this field. Therefore, efforts should be directed to broad investigations.

Graphical Abstract
Cell membrane-camouflaged inorganic nanoparticles for cancer therapy
Authors: Song Wanli , Jia Pengfei , Zhang Ting , Dou Keke , Liu Lubin , Ren Yaping , Liu Fujun , Xue Junmiao , Hasanin Mohamed Sayed , Qi Hongzhao , Zhou Qihui 
Published: June 2022

AbstractInorganic nanoparticles (INPs) have been paid great attention in the field of oncology in recent past years since they have enormous potential in drug delivery, gene delivery, photodynamic therapy (PDT), photothermal therapy (PTT), bio-imaging, driven motion, etc. To overcome the innate limitations of the conventional INPs, such as fast elimination by the immune system, low accumulation in tumor sites, and severe toxicity to the organism, great efforts have recently been made to modify naked INPs, facilitating their clinical application. Taking inspiration from nature, considerable researchers have exploited cell membrane-camouflaged INPs (CMCINPs) by coating various cell membranes onto INPs. CMCINPs naturally inherit the surface adhesive molecules, receptors, and functional proteins from the original cell membrane, making them versatile as the natural cells. In order to give a timely and representative review on this rapidly developing research subject, we highlighted recent advances in CMCINPs with superior unique merits of various INPs and natural cell membranes for cancer therapy applications. The opportunity and obstacles of CMCINPs for clinical translation were also discussed. The review is expected to assist researchers in better eliciting the effect of CMCINPs for the management of tumors and may catalyze breakthroughs in this area.

Graphical Abstract
Research can be integrated into public health policy-making: global lessons for and from Spanish economic evaluations
Authors: Trapero-Bertran Marta , Pokhrel Subhash , Hanney Stephen 
Published: June 2022

AbstractWHO promotes the use of research in policy-making to drive improvements in health, including in achieving Sustainable Development Goals such as tobacco control. The European Union’s new €95 billion Horizon Europe research framework programme parallels these aims, and also includes commitments to fund economic evaluations. However, researchers often express frustration at the perceived lack of attention to scientific evidence during policy-making. For example, some researchers claim that evidence regarding the return on investment from optimal implementation of evidence-based policies is frequently overlooked. An increasingly large body of literature acknowledges inevitable barriers to research use, but also analyses facilitators encouraging such use. This opinion piece describes how some research is integrated into policy-making. It highlights two recent reviews. One examines impact assessments of 36 multi-project research programmes and identifies three characteristics of projects more likely to influence policy-making. These include a focus on healthcare system needs, engagement of stakeholders, and research conducted for organizations supported by structures to receive and use evidence. The second review suggests that such characteristics are likely to occur as part of a comprehensive national health research system strategy, especially one integrated into the healthcare system. We also describe two policy-informing economic evaluations conducted in Spain. These examined the most cost-effective package of evidence-based tobacco control interventions and the cost-effectiveness of different strategies to increase screening coverage for cervical cancer. Both projects focused on issues of healthcare concern and involved considerable stakeholder engagement. The Spanish examples reinforce some lessons from the global literature and, therefore, could help demonstrate to authorities in Spain the value of developing comprehensive health research systems, possibly following the interfaces and receptor model. The aim of this would be to integrate needs assessment and stakeholder engagement with structures spanning the research and health systems. In such structures, economic evaluation evidence could be collated, analysed by experts in relation to healthcare needs, and fed into both policy-making as appropriate, and future research calls. The increasingly large local and global evidence base on research utilization could inform detailed implementation of this approach once accepted as politically desirable. Given the COVID-19 pandemic, increasing the cost-effectiveness of healthcare systems and return on investment of public health interventions becomes even more important.