bluuebunny/crossref_metadata_2025 huggingface dataset:
A Descriptive and Quantitative Immunohistochemical Study Demonstrating a Spectrum of Platelet Recruitment Patterns Across Pulmonary Infections Including COVID-19
Authors: McMullen Phillip D , Cho Joseph H , Miller Jonathan L , Husain Aliya N , Pytel Peter , Krausz Thomas
Published: October 2020

Objectives

Pulmonary platelet deposition and microangiopathy are increasingly recognized components of coronavirus disease 2019 (COVID-19) infection. Thrombosis is a known component of sepsis and disseminated intravascular coagulation. We sought to compare the level of platelet deposition in the pulmonary vasculature in cases of confirmed COVID-19 infection to other lung injuries and infections.

Methods

Immunohistochemistry was performed on 27 autopsy cases and 2 surgical pathology cases targeting CD61. Multiple cases of normal lung, diffuse alveolar damage, COVID-19, influenza, and bacterial and fungal infections, as well as one case of pulmonary emboli, were included. The levels of CD61 staining were compared quantitatively in the autopsy cases, and patterns of staining were described.

Results

Nearly all specimens exhibited an increase in CD61 staining relative to control lung tissue. The area of CD61 staining in COVID-19 infection was higher than influenza but still comparable to many other infectious diseases. Cases of aspiration pneumonia, Staphylococcus aureus infection, and blastomycosis exhibited the highest levels of CD61 staining.

Conclusions

Platelet deposition is a phenomenon common to many pulmonary insults. A spectrum of staining patterns was observed, suggestive of pathogen-specific mechanisms of platelet deposition. Further study into the mechanisms driving platelet deposition in pulmonary injuries and infections is warranted.
Patient outcomes following state-mandated opioid dose reductions
Authors: Hill Gabrielle , Hughes-Stricklett Alisa
Published: October 2020

Purpose

Maine Public Law Chapter 488 required that all opioid doses be reduced to below 100 morphine milligram equivalent (MME) by July 1, 2017, and VA Maine Healthcare System implemented policies consistent with the state law. The purpose of this study was to assess self-reported pain scores over 2 years and overall utilization of alternative healthcare services for veterans who were using opioid doses in excess of 100 MME prior to the implementation of policies consistent with Maine PL Chapter 488 in the VA Maine Healthcare System.

Methods

In this retrospective chart review, veterans were selected for inclusion if they were receiving chronic opioid therapy at the VA Maine Healthcare System of at least 100 MME daily in March 2016 according to the opioid therapy risk report (OTRR). Self-reported pain scores and use of alternative healthcare services were evaluated using VA Computerized Patient Record System (CPRS) data.

Results

Of the 147 patients evaluated per protocol, 75 patients (51%) did not have a clinically significant change in self-reported pain scores, and the self-reported pain scores of 29 patients (20%) improved from March 2016 to March 2018 (P = 0.054).

Conclusion

We found that mandatory dose reductions of chronic opioid medications did not result in a clinically or statistically significant worsening of self-reported pain scores. Our study suggests that opioid dose reductions may not negatively impact a patient’s functioning and pain intensity and calls into question the use of long-term opioid therapy for pain given the safety implications.
Recent advances in network-based methods for disease gene prediction
Authors: Ata Sezin Kircali , Wu Min , Fang Yuan , Ou-Yang Le , Kwoh Chee Keong , Li Xiao-Li
Published: October 2020

Disease–gene association through genome-wide association study (GWAS) is an arduous task for researchers. Investigating single nucleotide polymorphisms that correlate with specific diseases needs statistical analysis of associations. Considering the huge number of possible mutations, in addition to its high cost, another important drawback of GWAS analysis is the large number of false positives. Thus, researchers search for more evidence to cross-check their results through different sources. To provide the researchers with alternative and complementary low-cost disease–gene association evidence, computational approaches come into play. Since molecular networks are able to capture complex interplay among molecules in diseases, they become one of the most extensively used data for disease–gene association prediction. In this survey, we aim to provide a comprehensive and up-to-date review of network-based methods for disease gene prediction. We also conduct an empirical analysis on 14 state-of-the-art methods. To summarize, we first elucidate the task definition for disease gene prediction. Secondly, we categorize existing network-based efforts into network diffusion methods, traditional machine learning methods with handcrafted graph features and graph representation learning methods. Thirdly, an empirical analysis is conducted to evaluate the performance of the selected methods across seven diseases. We also provide distinguishing findings about the discussed methods based on our empirical analysis. Finally, we highlight potential research directions for future studies on disease gene prediction.
Computational prediction of species-specific yeast DNA replication origin via iterative feature representation
Authors: Manavalan Balachandran , Basith Shaherin , Shin Tae Hwan , Lee Gwang
Published: October 2020

Deoxyribonucleic acid replication is one of the most crucial tasks taking place in the cell, and it has to be precisely regulated. This process is initiated in the replication origins (ORIs), and thus it is essential to identify such sites for a deeper understanding of the cellular processes and functions related to the regulation of gene expression. Considering the important tasks performed by ORIs, several experimental and computational approaches have been developed in the prediction of such sites. However, existing computational predictors for ORIs have certain curbs, such as building only single-feature encoding models, limited systematic feature engineering efforts and failure to validate model robustness. Hence, we developed a novel species-specific yeast predictor called yORIpred that accurately identify ORIs in the yeast genomes. To develop yORIpred, we first constructed optimal 40 baseline models by exploring eight different sequence-based encodings and five different machine learning classifiers. Subsequently, the predicted probability of 40 models was considered as the novel feature vector and carried out iterative feature learning approach independently using five different classifiers. Our systematic analysis revealed that the feature representation learned by the support vector machine algorithm (yORIpred) could well discriminate the distribution characteristics between ORIs and non-ORIs when compared with the other four algorithms. Comprehensive benchmarking experiments showed that yORIpred achieved superior and stable performance when compared with the existing predictors on the same training datasets. Furthermore, independent evaluation showcased the best and accurate performance of yORIpred thus underscoring the significance of iterative feature representation. To facilitate the users in obtaining their desired results without undergoing any mathematical, statistical or computational hassles, we developed a web server for the yORIpred predictor, which is available at: http://thegleelab.org/yORIpred.
SSMD: a semi-supervised approach for a robust cell type identification and deconvolution of mouse transcriptomics data
Authors: Lu Xiaoyu , Tu Szu-Wei , Chang Wennan , Wan Changlin , Wang Jiashi , Zang Yong , Ramdas Baskar , Kapur Reuben , Lu Xiongbin , Cao Sha , Zhang Chi
Published: October 2020

Deconvolution of mouse transcriptomic data is challenged by the fact that mouse models carry various genetic and physiological perturbations, making it questionable to assume fixed cell types and cell type marker genes for different data set scenarios. We developed a Semi-Supervised Mouse data Deconvolution (SSMD) method to study the mouse tissue microenvironment. SSMD is featured by (i) a novel nonparametric method to discover data set-specific cell type signature genes; (ii) a community detection approach for fixing cell types and their marker genes; (iii) a constrained matrix decomposition method to solve cell type relative proportions that is robust to diverse experimental platforms. In summary, SSMD addressed several key challenges in the deconvolution of mouse tissue data, including: (i) varied cell types and marker genes caused by highly divergent genotypic and phenotypic conditions of mouse experiment; (ii) diverse experimental platforms of mouse transcriptomics data; (iii) small sample size and limited training data source and (iv) capable to estimate the proportion of 35 cell types in blood, inflammatory, central nervous or hematopoietic systems. In silico and experimental validation of SSMD demonstrated its high sensitivity and accuracy in identifying (sub) cell types and predicting cell proportions comparing with state-of-the-arts methods. A user-friendly R package and a web server of SSMD are released via https://github.com/xiaoyulu95/SSMD.
GalaxyCloudRunner: enhancing scalable computing for Galaxy
Authors: Goonasekera Nuwan , Mahmoud Alexandru , Chilton John , Afgan Enis
Published: October 2020

The existence of more than 100 public Galaxy servers with service quotas is indicative of the need for an increased availability of compute resources for Galaxy to use. The GalaxyCloudRunner enables a Galaxy server to easily expand its available compute capacity by sending user jobs to cloud resources. User jobs are routed to the acquired resources based on a set of configurable rules and the resources can be dynamically acquired from any of four popular cloud providers (AWS, Azure, GCP or OpenStack) in an automated fashion.

Availability and implementation

GalaxyCloudRunner is implemented in Python and leverages Docker containers. The source code is MIT licensed and available at https://github.com/cloudve/galaxycloudrunner. The documentation is available at http://gcr.cloudve.org/.
Abnormal Behavior and Cortical Connectivity Deficits in Mice Lacking Usp9x
Authors: Kasherman Maria A , Currey Laura , Kurniawan Nyoman D , Zalucki Oressia , Vega Michelle Sanchez , Jolly Lachlan A , Burne Thomas H J , Wood Stephen A , Piper Michael
Published: October 2020

Genetic association studies have identified many factors associated with neurodevelopmental disorders such as autism spectrum disorder (ASD). However, the way these genes shape neuroanatomical structure and connectivity is poorly understood. Recent research has focused on proteins that act as points of convergence for multiple factors, as these may provide greater insight into understanding the biology of neurodevelopmental disorders. USP9X, a deubiquitylating enzyme that regulates the stability of many ASD-related proteins, is one such point of convergence. Loss of function variants in human USP9X lead to brain malformations, which manifest as a neurodevelopmental syndrome that frequently includes ASD, but the underlying structural and connectomic abnormalities giving rise to patient symptoms is unknown. Here, we analyzed forebrain-specific Usp9x knockout mice (Usp9x−/y) to address this knowledge gap. Usp9x−/y mice displayed abnormal communication and social interaction behaviors. Moreover, the absence of Usp9x culminated in reductions to the size of multiple brain regions. Diffusion tensor magnetic resonance imaging revealed deficits in all three major forebrain commissures, as well as long-range hypoconnectivity between cortical and subcortical regions. These data identify USP9X as a key regulator of brain formation and function, and provide insights into the neurodevelopmental syndrome arising as a consequence of USP9X mutations in patients.
Early initiation of PD therapy in elderly patients is associated with increased risk of death
Authors: Peng Yuan , Ye Hongjian , Yi Chunyan , Xiao Xi , Huang Xuan , Liu Ruihua , Diao Xiangwen , Mao Haiping , Yu Xueqing , Yang Xiao
Published: October 2020

Background

The effect of early initiation of dialysis on outcomes of patients with end-stage renal disease (ESRD) remains controversial. We conducted this study to investigate the association between the timing of peritoneal dialysis (PD) initiation and mortality in different age groups.

Methods

In this single-centre cohort study, incident patients receiving PD from 1 January 2006 to 31 December 2016 were enrolled. Patients were categorized into three groups according to the estimated glomerular filtration rate (eGFR) at the initiation of PD, with early, mid and late initiation of PD defined as eGFR ≥7.5, 5–7.5 and <5 mL/min/1.73 m2, respectively.

Results

A total of 2133 incident patients receiving PD were enrolled with a mean age of 47.1 years, 59.6% male and 25.3% with diabetes, of whom 1803 were young (age <65 years) and 330 were elderly (age ≥65 years). After multivariable adjustment, the overall and cardiovascular (CV) mortality risks for young patients receiving PD were not significantly different between these three groups. However, for elderly patients, early initiation of PD therapy was associated with increased risks of all-cause {hazard ratio [HR} 1.54 [95% confidence interval (CI) 1.06–2.25]} and CV [HR 2.07 (95% CI 1.24–3.48)] mortality compared with late initiation of PD, while no significant difference was observed in overall or CV mortality between the mid- and late-start groups.

Conclusions

No significant difference in mortality risk was found among the three levels of eGFR at PD therapy initiation in young patients, while early initiation of PD was associated with a higher risk of overall and CV mortality among elderly patients.
Residual Cardiovascular Risk at Low LDL: Remnants, Lipoprotein(a), and Inflammation
Authors: Hoogeveen Ron C , Ballantyne Christie M
Published: October 2020

Background

Current guidelines target low-density lipoprotein cholesterol (LDL-C) concentrations to reduce atherosclerotic cardiovascular disease (ASCVD) risk, and yet clinical trials demonstrate persistent residual ASCVD risk despite aggressive LDL-C lowering.

Content

Non–LDL-C lipid parameters, most notably triglycerides, triglyceride-rich lipoproteins (TGRLs), and lipoprotein(a), and C-reactive protein as a measure of inflammation are increasingly recognized as associated with residual risk after LDL-C lowering. Eicosapentaenoic acid in statin-treated patients with high triglycerides reduced both triglycerides and ASCVD events. Reducing TGRLs is believed to have beneficial effects on inflammation and atherosclerosis. High lipoprotein(a) concentrations increase ASCVD risk even in individuals with LDL-C < 70 mg/dL. Although statins do not generally lower lipoprotein(a), proprotein convertase subtilisin/kexin type 9 inhibitors reduce lipoprotein(a) and cardiovascular outcomes, and newer approaches are in development. Persistent increases in C-reactive protein after intensive lipid therapy have been consistently associated with increased risk for ASCVD events.

We review the evidence that biochemical assays to measure TGRLs, lipoprotein(a), and C-reactive protein are associated with residual risk in patients treated to low concentrations of LDL-C. Growing evidence supports a causal role for TGRLs, lipoprotein(a), and inflammation in ASCVD; novel therapies that target TGRLs, lipoprotein(a), and inflammation are in development to reduce residual ASCVD risk.
Cardiovascular magnetic resonance imaging in the UK Biobank: a major international health research resource
Authors: Raisi-Estabragh Zahra , Harvey Nicholas C , Neubauer Stefan , Petersen Steffen E
Published: October 2020

The UK Biobank (UKB) is a health research resource of major international importance, incorporating comprehensive characterization of >500 000 men and women recruited between 2006 and 2010 from across the UK. There is prospective tracking of health outcomes for all participants through linkages with national cohorts (death registers, cancer registers, electronic hospital records, and primary care records). The dataset has been enhanced with the UKB imaging study, which aims to scan a subset of 100 000 participants. The imaging protocol includes magnetic resonance imaging of the brain, heart, and abdomen, carotid ultrasound, and whole-body dual X-ray absorptiometry. Since its launch in 2015, over 48 000 participants have completed the imaging study with scheduled completion in 2023. Repeat imaging of 10 000 participants has been approved and commenced in 2019. The cardiovascular magnetic resonance (CMR) scan provides detailed assessment of cardiac structure and function comprising bright blood anatomic assessment (sagittal, coronal, and axial), left and right ventricular cine images (long and short axes), myocardial tagging, native T1 mapping, aortic flow, and imaging of the thoracic aorta. The UKB is an open access resource available to health researchers across all scientific disciplines from both academia and industry with no preferential access or exclusivity. In this paper, we consider how we may best utilize the UKB CMR data to advance cardiovascular research and review notable achievements to date.
Valorization of low-cost, carbon-rich substrates by edible ascomycetes and basidiomycetes grown on liquid cultures
Authors: Sarris Dimitris , Philippoussis Antonios , Mallouchos Athanasios , Diamantopoulou Panagiota
Published: October 2020

Three ascomycetes (Morchella vulgaris AMRL 36, M. elata AMRL 63, Tuber aestivum AMRL 364) and four basidiomycetes strains (Lentinula edodes AMRL 124 and 126, Agaricus bisporus AMRL 208 and 209) were screened for their ability to grow on liquid static flask cultures of glucose, glycerol, molasses and waste flour-rich hydrolysates with C/N ratio of 20 and produce biomass, exopolysaccharides and lipids. The profile of lipid fatty acids was also assessed. Selected strains were furthermore cultivated in C/N = 50. Results showed that substrate consumption, biomass formation and secondary metabolites production were strain, substrate and C/N ratio dependent. The maximum biomass (X), lipid (L) and exopolysaccharides (EPS) values noted were Xmax = 25.2 g/L (C/N = 20; molasses) and Lmax = 6.51 g/L (C/N = 50; rice cereal hydrolysates) by T. aestivum strain AMRL 364 and EPSmax = 2.41 g/L by M. elata strain AMRL 63 (C/N = 50; molasses), respectively. When C/N ratio of 50 was applied, biomass, lipid production and substrate consumption seem to be negatively affected in most of the trials. The adaptation and capability of the mushroom strains to be cultivated on substrates based on agro-industrial waste streams and infant food of expired shelf date offers the opportunity to set a circular oriented bioprocess.
Repurposing the anti-viral drug zidovudine (AZT) in combination with meropenem as an effective treatment for infections with multi-drug resistant, carbapenemase-producing strains ofKlebsiella pneumoniae
Authors: DeSarno Alexandra E , Parcell Benjamin J , Coote Peter J
Published: October 2020

Multi-drug resistant (MDR) Klebsiella pneumoniae represent a global threat to healthcare due to lack of effective treatments and high mortality rates. The aim of this research was to explore the potential of administering zidovudine (AZT) in combination with an existing antibiotic to treat resistant K. pneumoniae infections. Two MDR K. pneumoniae strains were employed, producing either the NDM-1 or KPC-3 carbapenemase. Efficacy of combinations of AZT with meropenem were compared with monotherapies against infections in Galleria mellonella larvae by measuring larval mortality and bacterial burden. The effect of the same combinations in vitro was determined via checkerboard and time-kill assays. In vitro, both K. pneumoniae strains were resistant to meropenem but were susceptible to AZT. In G. mellonella, treatment with either AZT or meropenem alone offered minimal therapeutic benefit against infections with either strain. In contrast, combination therapy of AZT with meropenem presented significantly enhanced efficacy compared to monotherapies. This was correlated with prevention of bacterial proliferation within the larvae but not elimination. Checkerboard assays showed that the interaction between AZT and meropenem was not synergistic but indifferent. In summary, combination therapy of AZT with meropenem represents a potential treatment for carbapenemase-producing MDR K. pneumoniae and merits further investigation.
SARS-CoV-2 RT-PCR profile in 298 Indian COVID-19 patients: a retrospective observational study
Authors: Bhattacharya Bisakh , Kumar Rohit , Meena Ved Prakash , Soneja Manish , Singh Amit , Das Rojaleen , Xess Ashit , Arif Nazneen , Vig Saurabh , Rastogi Vandana , Tiwari Pavan , Bhatnagar Sushma , Mohan Anant , Wig Naveet , Dar Lalit
Published: October 2020

Background: despite being in the 5th month of pandemic, knowledge with respect to viral dynamics, infectivity and RT-PCR positivity continues to evolve.

Aim: to analyse the SARS CoV-2 nucleic acid RT-PCR profiles in COVID-19 patients.

Design: it was a retrospective, observational study conducted at COVID facilities under AIIMS, New Delhi.

Methods: patients admitted with laboratory confirmed COVID-19 were eligible for enrolment. Patients with incomplete details, or only single PCR tests were excluded. Data regarding demographic details, comorbidities, treatment received and results of SARS-CoV-2 RT-PCR performed on nasopharyngeal and oropharyngeal swabs, collected at different time points, was retrieved from the hospital records.

Results: a total of 298 patients were included, majority were males (75·8%) with mean age of 39·07 years (0·6–88 years). The mean duration from symptom onset to first positive RT-PCR was 4·7 days (SD 3·67), while that of symptom onset to last positive test was 17·83 days (SD 6·22). Proportions of positive RT-PCR tests were 100%, 49%, 24%, 8·7% and 20·6% in the 1st, 2nd, 3rd, 4th and >4 weeks of illness. A total of 12 symptomatic patients had prolonged positive test results even after 3 weeks of symptom onset. Age > = 60 years was associated with prolonged RT-PCR positivity (statistically significant).

Conclusion: this study showed that the average period of PCR positivity is more than 2 weeks in COVID-19 patients; elderly patients have prolonged duration of RT-PCR positivity and requires further follow up.
Lifestyle Behavioral Factors and Integrative Successful Aging Among Puerto Ricans Living in the Mainland United States
Authors: Lee-Bravatti Michelle A , O’Neill H June , Wurth Renee C , Sotos-Prieto Mercedes , Gao Xiang , Falcon Luis M , Tucker Katherine L , Mattei Josiemer
Published: October 2020

Background

Few studies have assessed multidimensional models for predicting successful aging that incorporate both physical and cognitive-psychosocial elements among minority populations. This study aimed to establish a comprehensive lifestyle behavioral factors (cLBF) score and an integrative successful aging (ISA) score and explore their associations among older Puerto Rican adults.

Methods

Data were assessed from 889 adults (45–75 years) participating in the longitudinal (baseline and 2-year follow-up) Boston Puerto Rican Health Study. Higher cLBF score (range 0–10) indicates healthier behaviors (nonsmoking, lack of sedentarism, physical activity, high diet quality, and adequate sleep). The physical domain score of ISA included 8 components (functional impairment, hypertension, diabetes, cancer, cardiovascular disease, respiratory disease, arthritis, osteoporosis) and ranged 0–11. The cognitive-psychosocial domain of ISA included 5 components (cognitive impairment, depressive symptoms, social support, perceived stress, and self-rated health) and ranged 0–10. The sum of both domains comprised the ISA score, ranging 0–21. Higher scores of ISA and its domains indicate more successful aging.

Results

At 2 years, the mean ± SD of cLBF score was 4.9 ± 1.8, and ISA was 10.1 ± 3.3. In multivariable-adjusted models, cLBF score was significantly and positively associated with 2-year change in overall ISA (β [95% CI]: 0.15 [0.07, 0.24] points), in physical domain (0.09 [0.04, 0.13] points), and in cognitive-psychosocial domain (0.08 [0.02, 0.14] points).

Conclusions

Maintaining healthier lifestyle behaviors may contribute to successful aging through both physical and cognitive-psychosocial domains. The results support using a multidimensional definition of successful aging in Puerto Ricans and evaluating it in other populations.
Midlife Leukocyte Telomere Length as an Indicator for Handgrip Strength in Late Life
Authors: Chang Xuling , Chua Kevin Yiqiang , Wang Ling , Liu Jianjun , Yuan Jian-Min , Khor Chiea-Chuen , Heng Chew-Kiat , Koh Woon-Puay , Dorajoo Rajkumar
Published: October 2020

Background

Telomere attrition has been proposed as a hallmark of aging. We previously reported on the association between blood leukocyte telomere length (LTL) at midlife and risk of chronic diseases and mortality.

Methods

In this study, we investigated the effect of midlife LTL and genetic proxies on 5 markers of aging outcomes, namely handgrip strength, timed up-and-go (TUG), Singapore-modified Mini-Mental State Examination (SM-MMSE) scores, anxiety, and depression indices, measured after a median 20-year follow-up in the Singapore Chinese Health Study (N = 9581).

Results

We observed a significant association between midlife LTL and handgrip strength later in life (p = .004, padjust = .020), as well as a nominal significant association between midlife LTL and TUG later in life (p = .036, padjust = .180). The weighted Genetic Risk Score (wGRS) comprising 15 previously reported LTL reducing loci in East Asians was not significantly associated with handgrip strength. However, results from Structural Equation Modeling showed that the effect of this wGRS on handgrip strength was mediated through LTL (proportion of wGRS effect on handgrip strength mediated through LTL = 33.3%, p = .010).

Conclusions

Longer midlife LTL was associated with increased handgrip strength later in life.
In search of ‘community’: a critical review of community mental health services for women in African settings
Authors: Elias Lauren , Singh Aneeha , Burgess Rochelle A
Published: October 2020

Community is deemed a central resource for the improvement of health, across disciplines, contexts and conditions. However, what is meant by this term is rarely critically explored. In Global Mental Health, considerable efforts in recent years have been directed towards scaling up ‘community’ approaches, with variable success, creating the need to better understand approaches to its use. Our study contributes to this need, through a critical review of studies engaging with the term ‘community’ in relation to women’s mental health services in African settings. Our review explored 30 peer-reviewed articles from the past 15 years, which were systematically evaluated for quality of evidence. Studies were then analysed using a blend of conventional and directed content analysis to unpack perspectives on the term’s use in intervention and phenomenological studies. We identified four broad categories of community: (1) place (shared geographical location or institutional affiliation), (2) practice (belongingness to a shared activity or profession), (3) symbols (meanings and experiences associated with shared community life) and (4) identity (diagnostic identity around a mental health condition). Analysis identified community of place as the most common primary focus of interest across the sample, with 80% of papers referencing this dimension. We noted that in studies where communities of practice were the focus, this was in relation to leveraging local knowledge to inform or support service delivery of intervention programmes, often designed by outsiders. Implications for future policy and mental health services research are discussed.
How Do Campaigns Matter? Independents, Political Information, and the Enlightening Role of Campaigns in Mexico
Authors: Castro Cornejo Rodrigo
Published: October 2020

Based on the Mexican case, this study finds that voters who report low levels of campaign information are more likely to update their vote intention as election day gets closer. Moreover, in contrast to previous studies which argue that political campaigns mainly persuade voters to support candidates against their precampaign dispositions, this article shows that, by the end of the campaign, most voters support the candidate best aligned with their underlying political predispositions—partisanship and presidential approval. In other words, voters become enlightened. This effect is particularly important among independents, a portion of the electorate understudied by the literature on Latin American political behavior.
Determination of Casein Allergens in Extensively Hydrolyzed Casein Infant Formula by Liquid Chromatography-Tandem Mass Spectrometry
Authors: Hostetler Gregory L , Barber Cynthia M , Miklus Michael B , Prieto Pedro A
Published: October 2020

Background

The use of hypoallergenic infant formulas and the need for reliable tests to determine the presence of residual antigens have increased in parallel.

Objective

An LC-MS method for quantitation of casein was validated using incurred samples and a matrix-matched external standard curve.

Method

Powdered infant formula samples were extracted in a buffer of sodium deoxycholate and ammonium bicarbonate at 60°C and filtered through 7 kDa desalting columns. Samples were digested overnight with trypsin and precipitated with acid prior to analysis of marker peptides by tandem mass spectrometry.

Results

Based on three marker peptides, the linear range for casein was 1.8–42 μg/g of powdered infant formula with an LOQ of 1.8 μg/g. The determination coefficients (R2) for each curve were ≥0.99 for casein peptides. Method repeatability was ≤22% RSD and intermediate precision was ≤23% RSD; recovery of casein from incurred material (2–20 µg/g) ranged from 78% to 118%.

Conclusions

An LC-MS/MS method was developed and validated for confirmation of casein allergens in hypoallergenic infant formula.

Highlights

A method was developed to accurately and reliably quantify casein allergens in extensively hydrolyzed casein infant formula by LC-MS without the need for custom peptide standards.
A new genome allows the identification of genes associated with natural variation in aluminium tolerance inBrachiariagrasses
Authors: Worthington Margaret , Perez Juan Guillermo , Mussurova Saule , Silva-Cordoba Alexander , Castiblanco Valheria , Cardoso Arango Juan Andres , Jones Charlotte , Fernandez-Fuentes Narcis , Skot Leif , Dyer Sarah , Tohme Joe , Di Palma Federica , Arango Jacobo , Armstead Ian , De Vega Jose J
Published: October 2020

Toxic concentrations of aluminium cations and low phosphorus availability are the main yield-limiting factors in acidic soils, which represent half of the potentially available arable land. Brachiaria grasses, which are commonly sown as forage in the tropics because of their resilience and low demand for nutrients, show greater tolerance to high concentrations of aluminium cations (Al3+) than most other grass crops. In this work, we explored the natural variation in tolerance to Al3+ between high and low tolerant Brachiaria species and characterized their transcriptional differences during stress. We identified three QTLs (quantitative trait loci) associated with root vigour during Al3+ stress in their hybrid progeny. By integrating these results with a new Brachiaria reference genome, we identified 30 genes putatively responsible for Al3+ tolerance in Brachiaria. We observed differential expression during stress of genes involved in RNA translation, response signalling, cell wall composition, and vesicle location homologous to aluminium-induced proteins involved in limiting uptake or localizing the toxin. However, there was limited regulation of malate transporters in Brachiaria, which suggests that exudation of organic acids and other external tolerance mechanisms, common in other grasses, might not be relevant in Brachiaria. The contrasting regulation of RNA translation and response signalling suggests that response timing is critical in high Al3+-tolerant Brachiaria.
PYL8 ABA receptors ofPhoenix dactyliferaplay a crucial role in response to abiotic stress and are stabilized by ABA
Authors: Garcia-Maquilon Irene , Coego Alberto , Lozano-Juste Jorge , Messerer Maxim , de Ollas Carlos , Julian Jose , Ruiz-Partida Rafael , Pizzio Gaston , Belda-Palazón Borja , Gomez-Cadenas Aurelio , Mayer Klaus F X , Geiger Dietmar , Alquraishi Saleh A , Alrefaei Abdulwahed F , Ache Peter , Hedrich Rainer , Rodriguez Pedro L
Published: October 2020

The identification of those prevalent abscisic acid (ABA) receptors and molecular mechanisms that trigger drought adaptation in crops well adapted to harsh conditions such as date palm (Phoenix dactylifera, Pd) sheds light on plant–environment interactions. We reveal that PdPYL8-like receptors are predominantly expressed under abiotic stress, with Pd27 being the most expressed receptor in date palm. Therefore, subfamily I PdPYL8-like receptors have been selected for ABA signaling during abiotic stress response in this crop. Biochemical characterization of PdPYL8-like and PdPYL1-like receptors revealed receptor- and ABA-dependent inhibition of PP2Cs, which triggers activation of the pRD29B-LUC reporter in response to ABA. PdPYLs efficiently abolish PP2C-mediated repression of ABA signaling, but loss of the Trp lock in the seed-specific AHG1-like phosphatase PdPP2C79 markedly impairs its inhibition by ABA receptors. Characterization of Arabidopsis transgenic plants that express PdPYLs shows enhanced ABA signaling in seed, root, and guard cells. Specifically, Pd27-overexpressing plants showed lower ABA content and were more efficient than the wild type in lowering transpiration at negative soil water potential, leading to enhanced drought tolerance. Finally, PdPYL8-like receptors accumulate after ABA treatment, which suggests that ABA-induced stabilization of these receptors operates in date palm for efficient boosting of ABA signaling in response to abiotic stress.
Compliance or Effectiveness? Assessing the Reach (and
Limits) of Treaty-Making
Authors: Martin Lisa L
Published: October 2020

This chapter considers the question of how treaties can work if their members do not comply with the treaty’s terms. It argues that treaty effectiveness has only a minimal relation to compliance as generally understood by treaty lawyers and scholars. Treaty lawyers tend to focus first and foremost on divining the contours of agreement — what terms can be negotiated and concluded? Once a treaty exists, their concerns shift to implementation with an eye to making — or avoiding — claims that a member has breached whatever obligations the treaty imposes. The chapter begins by describing how the extant literature conceptualizes and measures treaty compliance and effectiveness. It then focuses on distinguishing these two concepts, and emphasizes how questions of treaty effectiveness, not compliance, deserve higher priority. The final section offers some practical advice and principles for pursuing more effective treaty-making.
Who Can
Make Treaties? International Organizations
Authors: Elias Olufemi
Published: October 2020

International organizations (IOs) are subjects of international law typically created by agreement between States, usually through treaties, for the achievement or furtherance of a common objective of the IO’s creators. However, IOs also play a direct role in treaty-making. They have the capacity to become parties to treaties in their own right, within the scope of their competencies and where other parties are willing to enter into treaty relations with them. This chapter focuses on this direct role. It begins with an overview of the early practice regarding IOs as parties to treaties. Part II reviews the main issues in the 1986 Vienna Convention on the Law of Treaties (VCLT), including the ways in which it differs from the 1969 VCLT. Part III considers who is bound when an IO is a party to a treaty and Part IV reviews the types of treaties to which IOs are parties.
Managing the Process of Treaty Formation
Authors: Hinojal-Oyarbide Arancha
Published: October 2020

The formation of a treaty will often involve actors and acts beyond the parties and their communications inter se. This chapter analyses two of the most prominent examples of this phenomenon: (i) the role of the depositary of a multilateral treaty; and (ii) the obligation to register with the UN Secretariat bilateral and multilateral treaties and treaty formalities. The role of the depositary traditionally commences with the adoption of the treaty text that designates it as such. At that moment, the provisions regulating the legal procedures for the treaty to come into existence — the so-called ‘final clauses’ or ‘final provisions’ — become effective. Following adoption of a treaty’s text, the depositary normally prepares the original treaty. As the original must include all authentic languages, the text in all authentic languages must be submitted to the depositary.
Treaty Reservations
Authors: Swaine Edward T
Published: October 2020

This chapter examines current treaty law and practice relating to reservations. It is organized into five parts. Part I examines how reservations are made and distinguishes them from other unilateral acts. Part II examines the historical development of the legal rules surrounding reservations. Part III turns to the issues surrounding the initial legal status of reservations, including the continuing tension over whether all reservations must pass an initial threshold of permissibility to trigger the objection system envisaged by the 1969 Vienna Convention on the Law of Treaties. Part IV examines that objection system. Finally, Part V considers questions of authority, examining which actors have (or claim) authority to evaluate reservations.
The
Interpretation of Treaties over Time
Authors: Bjorge Eirik , Kolb Robert
Published: October 2020

This chapter considers an issue that has garnered sustained attention by States and international courts and tribunals in recent years — the potential to allow (or deny) evolutionary interpretations to treaty terms. It highlights five conclusions about the interpretation of treaties over time. First, evolutionary interpretations are made based on an array of means of ordinary interpretation, as enshrined in Vienna Convention on the Law of the Treaties Articles 31–33 and customary international law. Second, evolutionary interpretation is an issue of fact and law arising in the circumstances of particular cases. Third, the main principle is that of ‘contemporaneous interpretation’, a term referring not to the interpreter but to the parties (i.e. contemporaneous to the time of conclusion of the treaty). Fourth, it makes no sense to apply the principle of contemporaneity in all circumstances, since there are some terms used in treaties that make legal sense only when understood to evolve over time. Finally, to keep the unity of the treaty and its terms, the new interpretation is retrospective, having effect back to the time of the treaty’s conclusion.
Specialized Rules of Treaty Interpretation
Authors: Brölmann Catherine
Published: October 2020

International law has generally treated questions of the legal personality and legal powers of international organizations (IOs) as a distinct subject — notably one of international institutional law. However, IOs also regularly trigger questions of treaty law and practice. Most IOs are created by treaty, and that ‘constituent instrument’ provides the necessary starting point for delimiting their functions and competences. This chapter addresses treaty interpretation in the IO context, with particular attention to the interpretation of founding or constitutive treaties of international organizations. Part I examines the interpretation of constitutive treaties and IO secondary rules. Part II looks at the role of organizations as treaty interpreters. Examples are drawn predominantly from the UN context and, to a lesser degree, the European Union.
Exceptional Circumstances and Treaty
Commitments
Authors: Fitzmaurice Malgosia
Published: October 2020

This chapter deals with the existence of ‘exceptional circumstances’ that States can invoke to avoid (or remove) their treaty obligations. The following doctrines that may serve this purpose are analysed: (i) supervening impossibility of performance; (ii) fundamental change of circumstances; and (iii) necessity. The first two grounds are codified in Articles 61 and 62 of the 1969 Vienna Convention on the Law of Treaties. Necessity belongs to the realm of State responsibility (namely, Article 25 of the International Law Commission’s Articles on State Responsibility). As with the broader relationship between the law of treaties and the law of State responsibility, the doctrine of necessity’s relationship with the law of treaties remains unclear and, despite certain case law, it is one of the most taxing areas of international law.
Specifically Protected Persons and Objects
Authors: Geiß Robin , Paulussen Christophe
Published: October 2020

This chapter addresses the categories of persons and objects which receive specific protection under international humanitarian law (IHL), typically because they are seen as particularly vulnerable. In addition to the legal protection granted to the wounded and sick, contemporary IHL specifically regulates religious personnel; medical units and transports; persons and objects displaying the distinctive emblem; humanitarian relief personnel and objects; personnel and objects involved in peacekeeping missions; journalists; women; children; missing persons; hospital and safety zones; cultural property; and the environment. However, current practice shows that these categories continue to be vulnerable and that respect for the implementation of IHL is often lacking, with the repugnant practices of Islamic State (IS) as the new nadir. Therefore, the enforcement of IHL, through the application of international criminal law, either at the national or international level, is of the utmost importance to show that conduct violating IHL will not be tolerated. An interesting and hopeful sign in that respect is the prosecution of Al Faqi Al Mahdi before the International Criminal Court (ICC).
The Function of Truth and the Conservativeness Argument
Authors: Fujimoto Kentaro
Published: October 2020

Truth is often considered to be a logico-linguistic tool for expressing indirect endorsements and infinite conjunctions. In this article, I will point out another logico-linguistic function of truth: to enable and validate what I call a blind argument, namely, an argument that involves indirectly endorsed statements. Admitting this function among the logico-linguistic functions of truth has some interesting consequences. In particular, it yields a new type of so-called conservativeness argument, which poses a new type of threat to deflationism about truth.
Hydrodynamic simulations of an isolated star-forming gas cloud in the Virgo cluster
Authors: Calura Francesco , Bellazzini Michele , D’Ercole Annibale
Published: October 2020

We present a suite of three-dimensional, high-resolution hydrodynamic simulations that follow the evolution of a massive (107 M⊙) pressure-confined, star-forming neutral gas cloud moving through a hot intracluster medium (ICM). The main goal of the analysis is to get theoretical insight into the lifetimes and evolution of stellar systems like the recently discovered star-forming cloud SECCO 1 in the Virgo cluster of galaxies, but it may be of general interest for the study of the star-forming gas clumps that are observed in the tails of ram pressure stripped galaxies. Building up on a previous, simple simulation, we explored the effect of different relative velocity of the cloud and larger temperature of the ICM, as well as the effect of the cloud self-gravity. Moreover, we performed a simulation including star formation and stellar feedback, allowing for a first time a direct comparison with the observed properties of the stars in the system. The survivability of the cold gas in the simulated clouds is granted on time-scales of the order of 1 Gyr, with final cold gas fractions generally >0.75. In all cases, the simulated systems end up, after 1 Gyr of evolution, as symmetric clouds in pressure equilibrium with the external hot gas. We also confirm that gravity played a negligible role at the largest scales on the evolution of the clouds. In our simulation with star formation, star formation begins immediately, it peaks at the earliest times, and decreases monotonically with time. Inhomogeneous supernova explosions are the cause of an asymmetric shape of the gas cloud, facilitating the development of instabilities and the decrease of the cold gas fraction.
Searching for cross-correlation between stochastic gravitational-wave background and galaxy number counts
Authors: Yang Kate Z , Mandic Vuk , Scarlata Claudia , Banagiri Sharan
Published: October 2020

Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) and Advanced Virgo have recently published the upper limit measurement of persistent directional stochastic gravitational-wave background (SGWB) based on data from their first and second observing runs. In this paper, we investigate whether a correlation exists between this maximal likelihood SGWB map and the electromagnetic (EM) tracers of matter structure in the Universe, such as galaxy number counts. The method we develop will improve the sensitivity of future searches for anisotropy in the SGWB and expand the use of SGWB anisotropy to probe the formation of structure in the Universe. In order to compute the cross-correlation, we used the spherical harmonic decomposition of SGWB in multiple frequency bands and converted them into pixel-based sky maps in healpix basis. For the EM part, we use the Sloan Digital Sky Survey alaxy catalogue and form healpix sky maps of galaxy number counts at the same angular resolution as the SGWB maps. We compute the pixel-based coherence between these SGWB and galaxy count maps. After evaluating our results in different SGWB frequency bands and in different galaxy redshift bins, we conclude that the coherence between the SGWB and galaxy number count maps is dominated by the null measurement noise in the SGWB maps, and therefore not statistically significant. We expect the results of this analysis to be significantly improved by using the more sensitive upcoming SGWB measurements based on the third observing run of Advanced LIGO and Advanced Virgo.