bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial use and production system shape the fecal, environmental, and slurry resistomes of pig farms
Authors: Mencía-Ares Oscar , Cabrera-Rubio Raúl , Cobo-Díaz José Francisco , Álvarez-Ordóñez Avelino , Gómez-García Manuel , Puente Héctor , Cotter Paul D. , Crispie Fiona , Carvajal Ana , Rubio Pedro , Argüello Héctor 
Published: November 2020

Abstract
Background
The global threat of antimicrobial resistance (AMR) is a One Health problem impacted by antimicrobial use (AMU) for human and livestock applications. Extensive Iberian swine production is based on a more sustainable and eco-friendly management system, providing an excellent opportunity to evaluate how sustained differences in AMU impact the resistome, not only in the animals but also on the farm environment. Here, we evaluate the resistome footprint of an extensive pig farming system, maintained for decades, as compared to that of industrialized intensive pig farming by analyzing 105 fecal, environmental and slurry metagenomes from 38 farms.

Results
Our results evidence a significantly higher abundance of antimicrobial resistance genes (ARGs) on intensive farms and a link between AMU and AMR to certain antimicrobial classes. We observed differences in the resistome across sample types, with a higher richness and dispersion of ARGs within environmental samples than on those from feces or slurry. Indeed, a deeper analysis revealed that differences among the three sample types were defined by taxa-ARGs associations. Interestingly, mobilome analyses revealed that the observed AMR differences between intensive and extensive farms could be linked to differences in the abundance of mobile genetic elements (MGEs). Thus, while there were no differences in the abundance of chromosomal-associated ARGs between intensive and extensive herds, a significantly higher abundance of integrons in the environment and plasmids, regardless of the sample type, was detected on intensive farms.

Conclusions
Overall, this study shows how AMU, production system, and sample type influence, mainly through MGEs, the profile and dispersion of ARGs in pig production.
Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: a single-dose and two-period crossover randomized study
Authors: Li Xin , Wang Chenjing , Li Ting , Liu Yanping , Liu Shuqin , Tao Ye , Ma Yaping , Gao Xiaomeng , Cao Yu 
Published: November 2020

Abstract
Background
Levamlodipine, a calcium channel blocker, has been show act as a cardiovascular drug. To compare the pharmacokinetic parameters between levamlodipine (test formulation) at a single dose of 5 mg and amlodipine (reference formulation) at a single dose of 10 mg, the bioequivalence study was carried out.

Methods
A single-dose randomized, open-label, two-period crossover study was designed in healthy Chinese subjects. 48 subjects were divided into fasted and fed groups equally. The subjects randomly received the test or reference formulations at the rate of 1:1. Following a 21-day washout period, the alternative formulations were received. The blood samples were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 h later. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine the plasma concentrations of levamlodipine. Adverse events were recorded.

Results
The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ under both fasted and fed conditions were within the prespecified bioequivalence limits between 80 ~ 125%. Under fasted conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.70 ± 0.49) ng/mL, AUC0-t was (141.32 ± 36.24) ng × h/mL and AUC0-∞ was (157.14 ± 45.65) ng × h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.83 ± 0.52) ng/mL, AUC0-t was (153.62 ± 33.96) ng × h/mL and AUC0-∞ was (173.05 ± 41.78) ng × h/mL after a single dose of 10 mg amlodipine. Under fed conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.73 ± 0.55) ng/mL, AUC0-t was (166.93 ± 49.96) ng × h/mL and AUC0-∞ was (190.99 ± 70.89) ng × h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.87 ± 0.81) ng/mL AUC0-t was (165.46 ± 43.58) ng × h/mL and AUC0-∞ was (189.51 ± 64.70) ng × h/mL after a single dose of 10 mg amlodipine. Serious adverse event was not observed.

Conclusion
The trial confirmed that levamlodipine at a single dose of 5 mg and amlodipine at a single dose of 10 mg were bioequivalent under both fasted condition and fed condition.

Trial registration
Cinicaltrials, NCT04411875. Registered 3 June 2020 - Retrospectively registered
Supra-company apprenticeship training in Austria: a synopsis of empirical findings on a possibly early phase of a new pillar within VET
Authors: Schlögl Peter , Mayerl Martin , Löffler Roland , Schmölz Alexander 
Published: November 2020

AbstractSince 2008, the Austrian Vocational Training Act has given young people the opportunity to obtain vocational qualifications in supra-company training workshops. In addition to the traditional full-time vocational school system and company-based apprenticeship training, a third vocational qualification path has thus been established. This article presents empirical findings on this innovation in skill formation and examines the question of whether conditions for the sustainable establishment of a third pillar for acquiring vocational qualifications are given with regard to regulatory, normative, and cultural cognitive dimensions.
Functional genomic analyses uncover APOE-mediated regulation of brain and cerebrospinal fluid beta-amyloid levels in Parkinson disease
Authors: Ibanez Laura , Bahena Jorge A. , Yang Chengran , Dube Umber , Farias Fabiana H. G. , Budde John P. , Bergmann Kristy , Brenner-Webster Carol , Morris John C. , Perrin Richard J. , Cairns Nigel J. , O’Donnell John , Álvarez Ignacio , Diez-Fairen Monica , Aguilar Miquel , Miller Rebecca , Davis Albert A. , Pastor Pau , Kotzbauer Paul , Campbell Meghan C. , Perlmutter Joel S. , Rhinn Herve , Harari Oscar , Cruchaga Carlos , Benitez Bruno A. 
Published: November 2020

AbstractAlpha-synuclein is the main protein component of Lewy bodies, the pathological hallmark of Parkinson’s disease. However, genetic modifiers of cerebrospinal fluid (CSF) alpha-synuclein levels remain unknown. The use of CSF levels of amyloid beta1–42, total tau, and phosphorylated tau181 as quantitative traits in genetic studies have provided novel insights into Alzheimer’s disease pathophysiology. A systematic study of the genomic architecture of CSF biomarkers in Parkinson’s disease has not yet been conducted. Here, genome-wide association studies of CSF biomarker levels in a cohort of individuals with Parkinson’s disease and controls (N = 1960) were performed. PD cases exhibited significantly lower CSF biomarker levels compared to controls. A SNP, proxy for APOE ε4, was associated with CSF amyloid beta1–42 levels (effect = − 0.5, p = 9.2 × 10−19). No genome-wide loci associated with CSF alpha-synuclein, total tau, or phosphorylated tau181 levels were identified in PD cohorts. Polygenic risk score constructed using the latest Parkinson’s disease risk meta-analysis were associated with Parkinson’s disease status (p = 0.035) and the genomic architecture of CSF amyloid beta1–42 (R2 = 2.29%; p = 2.5 × 10−11). Individuals with higher polygenic risk scores for PD risk presented with lower CSF amyloid beta1–42 levels (p = 7.3 × 10−04). Two-sample Mendelian Randomization revealed that CSF amyloid beta1–42 plays a role in Parkinson’s disease (p = 1.4 × 10−05) and age at onset (p = 7.6 × 10−06), an effect mainly mediated by variants in the APOE locus. In a subset of PD samples, the APOE ε4 allele was associated with significantly lower levels of CSF amyloid beta1–42 (p = 3.8 × 10−06), higher mean cortical binding potentials (p = 5.8 × 10−08), and higher Braak amyloid beta score (p = 4.4 × 10−04). Together these results from high-throughput and hypothesis-free approaches converge on a genetic link between Parkinson’s disease, CSF amyloid beta1–42, and APOE.
Characteristics of secondary-ruptured faults in the Aso Caldera triggered by the 2016 Mw 7.0 Kumamoto earthquake
Authors: Fukushima Yo , Ishimura Daisuke 
Published: November 2020

AbstractThe 16 April 2016 Mw 7.0 Kumamoto earthquake caused prominent fault displacements and crustal deformation, not only around the main rupture faults but also around numerous secondary-ruptured faults. The physics and characteristics of such secondary faulting have not yet been studied in detail. We investigated a set of two secondary faults that appeared at the timing of the Mw 7.0 quake in the Aso Caldera by mainly using synthetic aperture radar interferometry and fault slip modeling. The two faults were found to be associated with surface displacement offsets of several centimeters or more, in the oblique sense of right-lateral and vertical motion. Fault slip inversions found that the slip was dominantly in normal sense with smaller contribution from the right-lateral component. The deeper limit of the slips was estimated to be around 1.3 km, which may coincide with the boundary between the superficial sediment layer and the basement rock. The shallowness of the slip and the difference in the dip angles of the main secondary fault and the Mw 7.0 seismogenic fault suggest separation of the two fault systems, although the fault strike and sense of motions were similar. The amount of slip on the two secondary faults was larger than that expected from the scaling law derived from seismogenic faults, which may indicate the difference in the physics of seismogenic and secondary faultings.
Understanding subjective well-being: perspectives from psychology and public health
Authors: Das Kirti V. , Jones-Harrell Carla , Fan Yingling , Ramaswami Anu , Orlove Ben , Botchwey Nisha 
Published: November 2020

AbstractBackgroundIndividual subjective well-being (SWB) is essential for creating and maintaining healthy, productive societies. The literature on SWB is vast and dispersed across multiple disciplines. However, few reviews have summarized the theoretical and empirical tenets of SWB literature across disciplinary boundaries.MethodsWe cataloged and consolidated SWB-related theories and empirical evidence from the fields of psychology and public health using a combination of online catalogs of scholarly articles and online search engines to retrieve relevant articles. For both theories and determinants/correlates of SWB, PubMed, PsychINFO, and Google Scholar were used to obtain relevant articles. Articles for the review were screened for relevance, varied perspectives, journal impact, geographic location of study, and topicality. A core theme of SWB empirical literature was the identification of SWB determinants/correlates, and over 100 research articles were reviewed and summarized for this review.ResultsWe found that SWB theories can be classified into four groups: fulfillment and engagement theories, personal orientation theories, evaluative theories, and emotional theories. A critical analysis of the conflicts and overlaps between these theories reveals the lack of a coherent theoretical and methodological framework that would make empirical research systematically comparable. We found that determinants/correlates of SWB can be grouped into seven broad categories: basic demographics, socioeconomic status, health and functioning, personality, social support, religion and culture, and geography and infrastructure. However, these are rarely studied consistently or used to test theories.ConclusionsThe lack of a clear, unifying theoretical basis for categorizing and comparing empirical studies can potentially be overcome using an operationalizable criterion that focuses on the dimension of SWB studied, measure of SWB used, design of the study, study population, and types of determinants and correlates. From our review of the empirical literature on SWB, we found that the seven categories of determinants/correlates identified may potentially be used to improve the link between theory and empirical research, and that the overlap in the determinant/correlates as they relate to multiple theory categories may enable us to test theories in unison. However, doing so in the future would require a conscious effort by researchers in several areas, which are discussed.
Cell Banking of HEK293T cell line for clinical-grade lentiviral particles manufacturing
Authors: Perpiñá Unai , Herranz Cristina , Martín-Ibáñez Raquel , Boronat Anna , Chiappe Felipe , Monforte Verónica , Orpella-Aceret Gemma , González Ester , Olivé Myriam , Castella María , Suñé Guillermo , Urbano-Ispizua Álvaro , Delgado Julio , Juan Manel , Canals Josep M. 
Published: November 2020

Abstract
Background
Cell banks are widely used to preserve cell properties as well as to record and control the use of cell lines in biomedical research. The generation of cell banks for the manufacturing of Advanced Therapy Medicinal Products, such as cell and gene therapy products, must comply with current Good Manufacturing Practice regulations. The quality of the cell lines used as starting materials in viral-vector manufacturing processes must be also assessed.

Methods
Three batches of a Master Cell Bank and a Working Cell Bank of the HEK293T cell line were manufactured under current Good Manufacturing Practices regulations. Quality control tests were performed according to product specifications. Process validation includes the training of manufacturing personnel by performing simulation tests, and the continuous measurement of environmental parameters such as air particles and microorganisms. Cell number and viability of cryopreserved cells were periodically measured in order to define the stability of these cellular products.

Results
All batches of HEK293T Master and Working Cell Banks met the acceptance criteria of their specifications showing the robustness and homogeneity of the processes. In addition, both Master and Working Cell Banks maintained the defined cell viability and concentration over a 37 month-period after cryopreservation.

Conclusions
Manufacturing cell banks under Good Manufacturing Practice regulations for their use as raw materials or final cellular products is feasible. HEK293T cell banks were used to manufacture clinical-grade lentiviral particles for Chimeric Antigen Receptor T-cell based clinical trials.
Nutritive value and digestibility of macronutrients from sheep and alpaca skin hydrolysates as a new alternative in juvenile rainbow trout (Oncorhynchus mykiss) feeding
Authors: Araníbar-Araníbar Marcelino Jorge , Roque-Huanca Bernardo , Portocarrero-Prado Harnold Segundo , Rodríguez-Huanca Francisco Halley , del Pilar Blanco-Espezúa María , Araníbar-Béjar Heidi Karol , Foraquita-Choque Simón 
Published: November 2020

Abstract
Background
The protein source from fish meal is very important in trout feeding, but it is expensive and very scarce. Alternative nutrient sources are required to achieve sustainability as trout production rapidly grows in Peru. The objective of this research was to determine the proximate chemical composition and the apparent digestibility coefficient (ADC) of dry matter, organic matter, crude protein, crude fat, and digestible energy of hydrolyzed sheep (HSS) and alpaca (HSA) skins in juvenile rainbow trout.

Methods
A total of 450 fishes were randomly distributed in nine digestibility tanks, with 60.0 ± 1.32 g of initial weight and 6.4 kg/m3 of stocking density. The water quality parameters were as follows: pH 8.4, temperature 11.5 °C, and dissolved oxygen 6.2 mg/l. The skin hydrolysates were treated at 130 °C with 15 psi pressure for 120 min. Fish were fed a reference diet and an experimental diet containing 70% reference diet and 30% skin hydrolysate. The ingredients of the diets were mixed and then extruded at 95 °C with 4-mm diameter (Extruder Khal® EE800). The ADC was determined by the indirect method using insoluble ash as a non-digestible marker.

Results
The ADC in HSS and HSA was similar for dry matter (67.7 vs 69.1%), organic matter (66.9 vs 68.2%), crude protein (70.4 vs 70.1%), and digestible energy (3.35 vs 3.24 Mcal/kg DM), but crude fat values were different (12.3 vs 48.0%; p < 0.001, respectively).

Conclusion
The hydrolyzed sheep and alpaca skins had a high content of macronutrients with an acceptable apparent digestibility of nutrients, making them a viable alternative to improve the nutritive value of more economical feeds for rainbow trout feed.
RETRACTED ARTICLE: Does serum B lymphocyte chemoattractant protein13 (CXCL13) level correlate with parameters of disease activity and severity in rheumatoid arthritis? Clinical and musculoskeletal ultrasonographic assessment
Authors: Baraka Eman A. , Egilla Sami A. , Hamad Gamal A. , Khalil Maiada A. , Ahmed Shereen H. , Elbehisy Mona M. 
Published: November 2020

Abstract
Background
Rheumatoid arthritis (RA) affects about 1–3% of the population making it one of the most popular autoimmune diseases. Chemokines through switching on their receptors exert a climacteric role in RA pathogenesis. The purpose of this cross-sectional study was to quantify the serum levels of serum B lymphocyte chemoattractant protein13 (CXCL13) chemokine in recent onset RA patients and to correlate its levels with clinical, laboratory, and musculoskeletal ultrasonographic parameters (MSUS) of disease activity and severity.

Results
The mean serum CXCL13 value showed a significant increase in the RA patients (388.86 ± 283.63 pg/ml) than in the controls (62.94 ± 31.62 pg/ml) (P < 0.001). Highly active RA patients had significantly the highest mean of CXCL13 (mean ± SD 819.13 ± 191.05) compared with the moderately active RA patients (mean ± SD 284.95 ± 137.93) (P < 0.001) and the RA patients with low disease activity (mean ± SD 129.5 ± 21.27) (P < 0.001) and its levels were positively related with clinical disease activity and musculoskeletal ultrasonographic severity parameters.

Conclusion
Serum CXCL13 is correlated with clinical disease activity and MSUS disease severity that encourages its use for monitoring the activity and severity of synovitis in recent onset RA patients. Future studies to detect the effect of disease activity control by medications on CXCL13 levels and the effect of the CXCL13 antagonist on controlling RA disease activity and severity are recommended.
Snx3 is important for mammalian neural tube closure via its role in canonical and non-canonical WNT signaling
Authors: Brown Heather Mary , Murray Stephen A. , Northrup Hope , Au Kit Sing , Niswander Lee A. 
Published: November 2020

ABSTRACT
Disruptions in neural tube (NT) closure result in neural tube defects (NTDs). To understand the molecular processes required for mammalian NT closure, we investigated the role of Snx3, a sorting nexin gene. Snx3−/− mutant mouse embryos display a fully-penetrant cranial NTD. In vivo, we observed decreased canonical WNT target gene expression in the cranial neural epithelium of the Snx3−/− embryos and a defect in convergent extension of the neural epithelium. Snx3−/− cells show decreased WNT secretion, and live cell imaging reveals aberrant recycling of the WNT ligand-binding protein WLS and mis-trafficking to the lysosome for degradation. The importance of SNX3 in WNT signaling regulation is demonstrated by rescue of NT closure in Snx3−/− embryos with a WNT agonist. The potential for SNX3 to function in human neurulation is revealed by a point mutation identified in an NTD-affected individual that results in functionally impaired SNX3 that does not colocalize with WLS and the degradation of WLS in the lysosome. These data indicate that Snx3 is crucial for NT closure via its role in recycling WLS in order to control levels of WNT signaling.
PET measured hypoxia and MRI parameters in re-irradiated head and neck squamous cell carcinomas: findings of a prospective pilot study
Authors: Rogasch Julian , Beck Marcus , Stromberger Carmen , Hofheinz Frank , Ghadjar Pirus , Wust Peter , Budach Volker , Amthauer Holger , Tinhofer Ingeborg , Furth Christian , Walter-Rittel Thula C. , Zschaeck Sebastian 
Published: November 2020

Background: Tumor hypoxia measured by dedicated tracers like [18F]fluoromisonidazole (FMISO) is a well-established prognostic factor in head and neck squamous cell carcinomas (HNSCC) treated with definitive chemoradiation (CRT). However, prevalence and characteristics of positron emission tomography (PET) measured hypoxia in patients with relapse after previous irradiation is missing. Here we report imaging findings of a prospective pilot study in HNSCC patients treated with re-irradiation. Methods: In 8 patients with recurrent HNSCC, diagnosed at a median of 18 months after initial radiotherapy/CRT, [18F]fluorodeoxyglucose (FDG)-PET/CT (n=8) and FMISO-PET/MRI (n=7) or FMISO-PET/CT (n=1) were performed. Static FMISO-PET was performed after 180 min. MRI sequences in PET/MRI included diffusion-weighted imaging with apparent diffusion coefficient (ADC) values and contrast enhanced T1w imaging (StarVIBE). Lesions (primary tumor recurrence, 4; cervical lymph node, 1; both, 3) were delineated on FDG-PET and FMISO-PET data using a background-adapted threshold-based method. SUVmax and SUVmean in FDG- and FMISO-PET were derived, as well as maximum tumor-to-muscle ratio (TMRmax) and hypoxic volume with 1.6-fold muscle SUVmean (HV1.6) in FMISO-PET. Intensity of lesional contrast enhancement was rated relative to contralateral normal tissue. Average ADC values were derived from a 2D region of interest in the tumor. Results: In FMISO-PET, median TMRmax was 1.7 (range: 1.1-1.8). Median HV1.6 was 0.05 ml (range: 0-7.3 ml). Only in 2/8 patients, HV1.6 was ≥1.0 ml. In FDG-PET, median SUVmax was 9.3 (range: 5.0-20.1). On contrast enhanced imaging four lesions showed decreased and four lesions increased contrast enhancement compared to non-pathologic reference tissue. Median average ADC was 1,060 ×106 mm2/s (range: 840-1,400 ×106 mm2/s). Conclusions: This pilot study implies that hypoxia detectable by FMISO-PET may not be as prevalent as expected among loco-regional recurrent HNSCC. ADC values were only mildly reduced, and contrast enhancement was variable. The results require confirmation in larger sample sizes.
Mouth Cancer: the Maxillofacial Surgeon's perspective
Authors: Goodson Alexander MC , Parmar Satyesh , Praveen Prav , Idle Matthew , Martin Timothy 
Published: November 2020

This article summarizes current practice according to UK guidelines for the management of oral cancer from the perspective of the oral and maxillofacial surgeon. The article discusses the patient pathway, starting with recognition of sinister features by the general dental practitioner in primary care and referral to specialist oral and maxillofacial surgery services, followed by the multidisciplinary approach to tumour staging, cancer treatment planning and delivery, and finally key issues in the ‘post-treatment’ phase of cancer care. Additional focus is provided for some of the surgical treatments and anatomical and physiological changes, of which the general dental practitioner should have some understanding. CPD/Clinical Relevance: General dental practitioners play a key role in the detection and early management of oral cancer, referring approximately 40% of all cases to secondary care. It is therefore important to understand key milestones and technical elements of the patient's journey.
A Practical Guide to Caries Prevention in Children
Authors: Rashid Mishaal , Ellis Amy , Deery Chris 
Published: November 2020

Caries is one of the most common diseases in the world and it is mostly preventable. Caries can have a large impact on a child's physical, social and mental health. There are a number of clinical interventions available to prevent caries and this article provides a summary of the general guidelines and tips on their implementation in relation to caries prevention in children. CPD/Clinical Relevance: This article highlights the importance of caries prevention and the relevant interventions, especially in the context of limited access to health services. These guidelines can be beneficial for all dental health professionals.