Miracle-dz/UniFAR-FTUs huggingface dataset:
Zika Virus IgM Detection and Neutralizing Antibody Profiles 12–19 Months after Illness Onset

Data on the duration of detectable Zika virus–specific IgM in infected persons are limited. Neutralizing antibody cross-reactivity occurs between Zika virus and related flaviviruses, but the degree to which this confounds diagnosis is uncertain. We tested serum specimens collected 12–19 months after illness onset from patients with confirmed Zika virus disease for Zika virus IgM and Zika virus and dengue virus neutralizing antibodies. Among 62 participants, 45 (73%) had detectable Zika virus IgM and 12 (19%) had an equivocal result. Although all patients tested had Zika virus neutralizing antibodies, 39 (63%) also had neutralizing antibodies against dengue virus; of those, 12 (19%) had <4-fold difference between Zika virus and dengue virus titers, and 5 (8%) had dengue virus titer >4-fold higher than Zika virus titer. Prolonged detection of IgM and neutralizing antibody cross-reactivity make it difficult to determine the timing of Zika virus infection and differentiate between related flaviviruses.
d-amino acid oxidase promotes cellular senescence via the production of reactive oxygen species

This study reveals a novel role of d-amino acid oxidase in promoting cellular senescence induced by genotoxic stresses via enzymatic generation of reactive oxygen species. d-amino acid oxidase (DAO) is a flavin adenine dinucleotide (FAD)–dependent oxidase metabolizing neutral and polar d-amino acids. Unlike l-amino acids, the amounts of d-amino acids in mammalian tissues are extremely low, and therefore, little has been investigated regarding the physiological role of DAO. We have recently identified DAO to be up-regulated in cellular senescence, a permanent cell cycle arrest induced by various stresses, such as persistent DNA damage and oxidative stress. Because DAO produces reactive oxygen species (ROS) as byproducts of substrate oxidation and the accumulation of ROS mediates the senescence induction, we explored the relationship between DAO and senescence. We found that inhibition of DAO impaired senescence induced by DNA damage, and ectopic expression of wild-type DAO, but not enzymatically inactive mutant, enhanced it in an ROS-dependent manner. Furthermore, addition of d-amino acids and riboflavin, a metabolic precursor of FAD, to the medium potentiated the senescence-promoting effect of DAO. These results indicate that DAO promotes senescence through the enzymatic ROS generation, and its activity is regulated by the availability of its substrate and coenzyme.
Anticholinergic Drug Induced Cognitive and Physical Impairment: Results from the InCHIANTI Study.

Background The aims of this study were to evaluate the relationship between anticholinergic drug burden (ACB) cognitive impairment, physical frailty and cognitive frailty, and determine if ACB is predictive of these phenotypes when modeled with biological and genomic biomarkers. Methods In a retrospective cohort study, a total of 1,453 adults aged 20-102 years was used to examine ACB as a predictor for cognitive impairment, physical frailty, and cognitive frailty. Anticholinergic burden is examined as a predictor for all phenotypes in a cross-sectional analysis using logistic, ordinal regression models, and Extreme Gradient Boosting for population predictive modeling. Results A significant association was found between ACB and cognitive decline (p = 0.02), frailty (p <.001) and cognitive frailty (p <.001). The odds of cognitive impairment increased by 1.21 (95% CI = 1.06-1.37, p <.001), odds of being frail increased by 1.33 (95% CI = 1.18-1.50, p <.001), and odds of having cognitive frailty increased by 1.36 (95% CI = 1.21-1.54, p <.001). Population modeling results indicated ACB score as one of the stronger predictors for cognitive impairment, physical frailty, and cognitive frailty with AUCs ranging from 0.81-0.88. Conclusions Anticholinergic medications are a potentially modifiable risk factor for the prevention of cognitive and physical decline. Identification of reversible causes for cognitive and physical impairment is critical for the aging population. These findings encourage new research that may lead to effective interventions for deprescribing programs for the prevention of cognitive and physical decline in older adults.
Nonclonal Chromosome Aberrations and Genome Chaos in Somatic and Germ Cells from Patients and Survivors of Hodgkin Lymphoma

Anticancer regimens for Hodgkin lymphoma (HL) patients include highly genotoxic drugs that have been very successful in killing tumor cells and providing a 90% disease-free survival at five years. However, some of these treatments do not have a specific cell target, damaging both cancerous and normal cells. Thus, HL survivors have a high risk of developing new primary cancers, both hematologic and solid tumors, which have been related to treatment. Several studies have shown that after treatment, HL patients and survivors present persistent chromosomal instability, including nonclonal chromosomal aberrations. The frequency and type of chromosomal abnormalities appear to depend on the type of therapy and the cell type examined. For example, MOPP chemotherapy affects hematopoietic and germ stem cells leading to long-term genotoxic effects and azoospermia, while ABVD chemotherapy affects transiently sperm cells, with most of the patients showing recovery of spermatogenesis. Both regimens have long-term effects in somatic cells, presenting nonclonal chromosomal aberrations and genomic chaos in a fraction of noncancerous cells. This is a source of karyotypic heterogeneity that could eventually generate a more stable population acquiring clonal chromosomal aberrations and leading towards the development of a new cancer.
Trait Openness and serotonin 2A receptors in healthy volunteers: A positron emission tomography study

Recent research found lasting increases in personality trait Openness in healthy individuals and patients after administration of the serotonin 2A receptor (5‐HT2AR) agonist psilocybin. However, no studies have investigated whether 5‐HT2AR availability as imaged using positron emission tomography (PET) is associated with this trait. In 159 healthy individuals (53 females), the association between 5‐HT2AR binding in neocortex imaged with [18F]altanserin or [11C]Cimbi‐36 PET and personality trait Openness was investigated using linear regression models. In these models the influence of sex on the association was also investigated. Trait Openness was assessed with the NEO Personality Inventory‐Revised. No significant associations between neocortical 5‐HT2AR binding and trait Openness were found for [18F]altanserin (p = 0.5) or [11C]Cimbi‐36 (p = 0.8). Pooling the data in a combined model did not substantially change our results (p = 0.4). No significant interactions with sex were found (p > 0.35). Our results indicate that differences in 5‐HT2AR availability are not related to variations in trait Openness in healthy individuals. Although stimulation of the 5‐HT2AR with compounds such as psilocybin may contribute to long‐term changes in trait Openness, there is no evidence in favor of an association between 5‐HT2AR and trait Openness.
Safety profile of human papilloma virus vaccines: an analysis of the US Vaccine Adverse Event Reporting System from 2007 to 2017

Human papilloma virus (HPV) is the cause of different types of carcinoma. Despite the remarkable effectiveness of the HPV vaccines, there have been many complaints about their risk–benefit profile due to adverse events following immunization (AEFI). The purpose of this study is to analyse the safety profile of the HPV vaccine basing on real‐life data derived from reports of suspected AEFIs collected in the US Vaccine Adverse Events Reporting System (VAERS) and assess if the searches on Google overlap with spontaneous reporting.
Individual Attributes, Values, and Goals of an All-Military Women Antarctic Expedition.

BACKGROUND: While participation of women in the military has increased, research on performance of female teams engaged in arduous physical activity in isolated, confined, and extreme (ICE) environments remains sparse.METHODS: A team of six British military women completed the Multidimensional Personality Questionnaire-Brief Form, Triarchic Psychopathy Measure, and Personal Values Questionnaire (PVQ) prior to embarking on an expedition that traversed the Antarctic continent. Questionnaires were completed weekly on the ice; repeat of the PVQ and individual semistructured debriefing interviews were carried out within 9 d post-expedition.RESULTS: Personality findings indicated a generally well-adjusted group with notable individual differences in personality and personal values. Positive affect and camaraderie among teammates was evident throughout, although pace vs. distance in the strategy of the daily trek was a continuing point of tension. Honesty in communication was viewed as key to team effectiveness. A significant post-expedition decline in the tradition value (Pre M = -0.55, SD = 0.99; Post M = -0.82, SD = 1.12) and an increase in the conformity value (Pre M = -0.26, SD = 0.46; Post M = 0.18, SD = 0.27) was found.DISCUSSION: Congruence in personal and team goals among group members engaged in highly challenging activities is crucial for optimal team performance. Presence of two highly dominant individuals has a negative effect on team dynamics. Application of study findings to space exploration is considered.Blackadder-Weinstein J, Leon GR, Norris RC, Venables NC, Smith M. Individual attributes, values, and goals of an all-military women Antarctic expedition. Aerosp Med Hum Perform. 2019; 90(1):18-25.
Genetic effects on promoter usage are highly context-specific and contribute to complex traits

Genetic variants regulating RNA splicing and transcript usage have been implicated in both common and rare diseases. Although transcript usage quantitative trait loci (tuQTLs) have now been mapped in multiple cell types and conditions, the molecular mechanisms through which these variants exert their effect have remained elusive. Specifically, changes in transcript usage could arise from promoter choice, alternative splicing or 3′ end choice, but current tuQTL studies have not been able to distinguish between them. Here, we performed comprehensive analysis of RNA-seq data from human macrophages exposed to a range of inflammatory stimuli (IFNγ, Salmonella, IFNγ + Salmonella) and a metabolic stimulus (acetylated LDL), obtained from up to 84 individuals. In addition to conventional gene-level and transcript-level analyses, we also developed an analytical approach to directly quantify promoter, internal exon and 3′ end usage. We found that although naive transcript-level analysis often links single genetic variants to multiple coupled changes on the transcriptome, this appears to be an artefact of incomplete transcript annotations. Most of this coupling disappears when promoters, splicing and 3′ end usage are quantified directly. Furthermore, promoter, splicing and 3′ end QTLs are each enriched in distinct genomic features, suggesting that they are predominantly controlled by independent regulatory mechanisms. We also find that promoter usage QTLs are 50% more likely to be context-specific than canonical splicing QTLs and constitute 25% of the transcript-level colocalisations with complex traits. Thus, promoter usage might be a previously underappreciated molecular mechanism mediating complex trait associations in a context-specific manner.
Neuroprotective Effect of Ilex Paraguariensis Intake on Brain Myelin of Lung Adenocarcinoma-Bearing Male Balb/c Mice

Abstract Ilex paraguariensis (IP) is widely consumed as tea with high nutritional value. This plant contains several bioactive phenolic compounds, which are antioxidant and anti-inflammatory. On the other hand, lung adenocarcinoma (LAC) deleteriously involves neoplastic progression, inflammatory paraneoplastic syndromes, and death. Given that brain is a frequent target of this illness, our objective was to determine the neuroprotective effect of IP consumption in LAC-bearing mice. They were orally treated with 50 mg of IP extract/kg/day (IP50) for 3 weeks. Results (phenolic compounds, lipid peroxides, interleukin 6-IL-6-, tumor necrosis factor alpha -TNFα-, and luxol-stained myelination) were compared with respect to untreated controls (C) by the T test. IP50 significantly lowed brain IL-6 (2858.12 ± 57.81 pg g−1 vs. 3801.30 ± 27.34 pg g−1), whereas other variables differed in a less extent. C brains showed demyelination (low luxol-staining contrast between gray and white matters), with IP50 increasing myelination (P < 0.05). In conclusion, LAC deleterious effects on murine brain were prevented by dietary IP, which is an original discovery to develop a nutritional approach against cancer neurological compromise.
Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients

Background and Purpose— This ARISTOPHANES study (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) used multiple data sources to compare stroke/systemic embolism (SE) and major bleeding (MB) among a large number of nonvalvular atrial fibrillation patients on non–vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods— A retrospective observational study of nonvalvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015, was conducted pooling Centers for Medicare and Medicaid Services Medicare data and 4 US commercial claims databases. After 1:1 NOAC-warfarin and NOAC-NOAC propensity score matching in each database, the resulting patient records were pooled. Cox models were used to evaluate the risk of stroke/SE and MB across matched cohorts. Results— A total of 285 292 patients were included in the 6 matched cohorts: 57 929 apixaban-warfarin, 26 838 dabigatran-warfarin, 83 007 rivaroxaban-warfarin, 27 096 apixaban-dabigatran, 62 619 apixaban-rivaroxaban, and 27 538 dabigatran-rivaroxaban patient pairs. Apixaban (hazard ratio [HR], 0.61; 95% CI, 0.54–0.69), dabigatran (HR, 0.80; 95% CI, 0.68–0.94), and rivaroxaban (HR, 0.75; 95% CI, 0.69–0.82) were associated with lower rates of stroke/SE compared with warfarin. Apixaban (HR, 0.58; 95% CI, 0.54–0.62) and dabigatran (HR, 0.73; 95% CI, 0.66–0.81) had lower rates of MB, and rivaroxaban (HR, 1.07; 95% CI, 1.02–1.13) had a higher rate of MB compared with warfarin. Differences exist in rates of stroke/SE and MB across NOACs. Conclusions— In this largest observational study to date on NOACs and warfarin, the NOACs had lower rates of stroke/SE and variable comparative rates of MB versus warfarin. The findings from this study may help inform the discussion on benefit and risk in the shared decision-making process for stroke prevention between healthcare providers and nonvalvular atrial fibrillation patients. Clinical Trial Registration— URL: https://www.clinicaltrials. gov/. Unique identifier: NCT03087487.
Protein glycosylation: Sweet or bitter for bacterial pathogens?

Abstract Protein glycosylation systems in many bacteria are often associated with crucial biological processes like pathogenicity, immune evasion and host-pathogen interactions, implying the significance of protein-glycan linkage. Similarly, host protein glycosylation has been implicated in antimicrobial activity as well as in promoting growth of beneficial strains. In fact, few pathogens notably modulate host glycosylation machineries to facilitate their survival. To date, diverse chemical and biological strategies have been developed for conjugate vaccine production for disease control. Bioconjugate vaccines, largely being produced by glycoengineering using PglB (the N-oligosaccharyltransferase from Campylobacter jejuni) in suitable bacterial hosts, have been highly promising with respect to their effectiveness in providing protective immunity and ease of production. Recently, a novel method of glycoconjugate vaccine production involving an O-oligosaccharyltransferase, PglL from Neisseria meningitidis, has been optimized. Nevertheless, many questions on defining antigenic determinants, glycosylation markers, species-specific differences in glycosylation machineries, etc. still remain unanswered, necessitating further exploration of the glycosylation systems of important pathogens. Hence, in this review, we will discuss the impact of bacterial protein glycosylation on its pathogenesis and the interaction of pathogens with host protein glycosylation, followed by a discussion on strategies used for bioconjugate vaccine development.
Dissipation Dynamics and Residue of Four Herbicides in Paddy Fields Using HPLC-MS/MS and GC-MS

The dissipation dynamics and residue of pyrazosulfuron-ethyl, bensulfuron-methyl, acetochlor, and butachlor in paddy fields at Good Agricultural Practices (GAP) condition were carefully investigated in this study. The four herbicides’ residues were determined based on a quick, easy, cheap, rugged, safe (QuEChERS) method coupled with HPLC-MS/MS and GC-MS. The limit of detection (LOD) for pyrazosulfuron-ethyl, bensulfuron-methyl, acetochlor, and butachlor in all matrices ranged from 0.04–1.0 ng. The limit of quantification (LOQ) of the four herbicides ranged from 0.01–0.1 mg/kg. Moreover, the average recoveries of the four herbicides ranged from 78.9–108% with relative standard deviations (RSDs) less than 15% at three different fortified levels for different matrices. The dissipation results indicated that the average half-lives (t1/2) of the four herbicides in soil were in the range of 3.5–17.8 days, and more than 95% of the four herbicides dissipated within 5 days in water. Furthermore, the final residues of the four herbicides were all below the LOQ at harvest time. Such results highlight the dissipation dynamics and residue of the four herbicides in a rice cropping system and contribute to risk assessment as well as scientific guidance on the proper and safe application of herbicides in paddy fields.
SS-HCNN: Semi-Supervised Hierarchical Convolutional Neural Network for Image Classification

The availability of large-scale annotated data and the uneven separability of different data categories have become two major impediments of deep learning for image classification. In this paper, we present a semi-supervised hierarchical convolutional neural network (SS-HCNN) to address these two challenges. A large-scale unsupervised maximum margin clustering technique is designed, which splits images into a number of hierarchical clusters iteratively to learn cluster-level CNNs at parent nodes and category-level CNNs at leaf nodes. The splitting uses the similarity of CNN features to group visually similar images into the same cluster, which relieves the uneven data separability constraint. With the hierarchical cluster-level CNNs capturing certain high-level image category information, the category-level CNNs can be trained with a small amount of labeled images, and this relieves the data annotation constraint. A novel cluster splitting criterion is also designed, which automatically terminates the image clustering in the tree hierarchy. The proposed SS-HCNN has been evaluated on the CIFAR-100 and ImageNet classification datasets. The experiments show that the SS-HCNN trained using a portion of labeled training images can achieve comparable performance with other fully trained CNNs using all labeled images. Additionally, the SS-HCNN trained using all labeled images clearly outperforms other fully trained CNNs.
Reducing Postpartum Weight Retention and Interpregnancy Weight Gain, an Important Goal Not Yet Realized

Elevated maternal BMI and excessive gestational weight gain are associated with increased risk of adverse pregnancy outcomes as well as postpartum weight retention and childhood obesity. There have been several randomized trials that have tested interventions for reducing gestational weight gain and subsequent adverse maternal and neonatal outcomes. Seven of these trials are part of the Lifestyle Interventions for Expectant Moms (LIFE-Moms) consortium, a collaborative group evaluating the effect of behavioral and lifestyle interventions among pregnant women with overweight and obesity (1). In this month’s issue of Obesity, Phelan and colleagues (2) present the 1-year postpartum maternal outcomes from the Healthy Beginnings/Comienzos Saludables trial. This high-quality study was novel in that it paired traditional behavioral weight management intervention techniques with the use of meal replacements during pregnancy. Previously published trial results demonstrated that intervention participants achieved a significantly lower average total gestational weight gain (9.4 vs. 11.2 kg) and a lower rate of gain (0.33 vs. 0.39 kg/wk) compared with controls (3). The intervention ended at delivery and 1-year follow-up was excellent. Unfortunately, despite the modest success of the intervention during pregnancy, there was neither a significant effect of the prenatal intervention on the odds of achieving prepregnancy weight by 1 year post partum nor a difference between the intervention and control groups in the magnitude of weight retained. The authors also found that the use of meal replacements, which were not provided by the study after delivery, was not sustained in the postpartum period.
The health and quality of life of Thalidomide survivors as they age – Evidence from a UK survey

Background In the late 1950s and early 1960s the drug Thalidomide was marketed across the world as a non-addictive tranquilizer. Despite being given to pregnant women as a safe treatment for morning sickness, Thalidomide caused serious damage to the unborn child. Much has been written about the drug and the birth defects it caused but evidence about the health of Thalidomide survivors as they age is limited. Aim The aim of this study was to: explore the health and wellbeing UK Thalidomide survivors; document the health problems experienced by them as they reach their mid-50s; and examine the impacts on their health-related quality of life and employment. Methods A health and wellbeing survey of 351 UK Thalidomide survivors, which gathered information about home and employment circumstances, recent health problems, and health related quality of life (using SF12 Health Survey). Overall analysis focused on descriptive statistics; the association between respondents’ health related quality of life and original impairment was examined using Pearson Correlation; and a three step Hierarchical Regression was used to explore the influence of five factors which narrative responses suggested might be important. Results As Thalidomide survivors reach their mid-50’s they are experiencing a wide range of secondary health problems, in particular musculoskeletal problems, and depression and anxiety, with multimorbidity a growing issue. These health problems are having a negative impact on their employment (two fifths are unable to work) and their physical health related quality of life, which is significantly poorer than the general population. Discussion Having lived relatively independent lives, many Thalidomide survivors are now having to adjust to growing disability. The study provides further evidence of the accumulative impact of disability over peoples’ lifetimes and highlights the value of a life course perspective in understanding the complex experience of growing older with a disability.