bluuebunny/crossref_metadata_2025 huggingface dataset:
Building capacity in mental health care in low- and middle-income countries by training primary care physicians using the mhGAP: a randomized controlled trial
Authors: Spagnolo Jessica , Champagne François , Leduc Nicole , Rivard Michèle , Melki Wahid , Piat Myra , Laporta Marc , Guesmi Imen , Bram Nesrine , Charfi Fatma
Published: October 2019

To address the rise in mental health conditions in Tunisia, a training based on the Mental Health Gap Action Programme (mhGAP) Intervention Guide (IG) was offered to primary care physicians (PCPs) working in the Greater Tunis area. Non-specialists (such as PCPs)’ training is an internationally supported way to target untreated mental health symptoms. We aimed to evaluate the programme’s impact on PCPs’ mental health knowledge, attitudes, self-efficacy and self-reported practice, immediately following and 18 months after training. We conducted an exploratory trial with a combination of designs: a pretest–posttest control group design and a one-group pretest–posttest design were used to assess the training’s short-term impact; and a repeated measures design was used to assess the training’s long-term impact. The former relied on a delayed-intervention strategy: participants assigned to the control group (Group 2) received the training after the intervention group (Group 1). The intervention consisted of a weekly mhGAP-based training session (totalling 6 weeks), comprising lectures, discussions, role plays and a support session offered by trainers. Data were collected at baseline, following Group 1’s training, following Group 2’s training and 18 months after training. Descriptive, bivariate and ANOVA analyses were conducted. Overall, 112 PCPs were randomized to either Group 1 (n = 52) or Group 2 (n = 60). The training had a statistically significant short-term impact on mental health knowledge, attitudes and self-efficacy scores but not on self-reported practice. When comparing pre-training results and results 18 months after training, these changes were maintained. PCPs reported a decrease in referral rates to specialized services 18 months after training in comparison to pre-training. The mhGAP-based training might be useful to increase mental health knowledge and self-efficacy, and decrease reported referral rates and negative mental health attitudes among PCPs in Tunisia and other low- and middle-income countries. Future studies should examine relationships among these outcome variables.
Genome aging: somatic mutation in the brain links age-related decline with disease and nominates pathogenic mechanisms
Authors: Lodato Michael A , Walsh Christopher A
Published: October 2019

Aging is a mysterious process, not only controlled genetically but also subject to random damage that can accumulate over time. While DNA damage and subsequent mutation in somatic cells were first proposed as drivers of aging more than 60 years ago, whether and to what degree these processes shape the neuronal genome in the human brain could not be tested until recent technological breakthroughs related to single-cell whole-genome sequencing. Indeed, somatic single-nucleotide variants (SNVs) increase with age in the human brain, in a somewhat stochastic process that may nonetheless be controlled by underlying genetic programs. Evidence from the literature suggests that in addition to demonstrated increases in somatic SNVs during aging in normal brains, somatic mutation may also play a role in late-onset, sporadic neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. In this review, we will discuss somatic mutation in the human brain, mechanisms by which somatic mutations occur and can be controlled, and how this process can impact human health.
Cytomegalovirus Genetic Diversity Following Primary Infection
Authors: Ross Shannon A , Pati Pravasini , Jensen Travis L , Goll Johannes B , Gelber Casey E , Singh Amy , McNeal Monica , Boppana Suresh B , Bernstein David I
Published: October 2019

Background

Infection with multiple cytomegalovirus (CMV) strains (mixed infection) was reported in a variety of hosts. As the virus genetic diversity in primary CMV infection and the changes over time remain incompletely defined, we examined CMV diversity and changes in diversity over time in healthy adolescent females who participated in a phase 2 CMV gB/MF59 vaccine trial.

Methods

CMV genetic diversity was determined by genotyping of 5 genes—gB (UL55), gH (UL75), gN (UL73), US28, and UL144—in urine, saliva, and plasma samples from 15 study subjects.

Results

At the time of primary infection, 5 of 12 (42%) urine samples had multiple virus strains, and 50% of vaccine recipients were infected with gB1 genotype (vaccine strain). Mixed infection was documented in all 15 subjects within 3 months after primary infection, and the majority had different CMV genotypes in different compartments. Changes in genotypes over time were observed in all subjects.

Conclusions

Infection with multiple CMV genotypes was common during primary infection and further diversification occurred over time. Infection with gB1 genotype in vaccine recipients suggests a lack of strain-specific protection from the vaccine. As only 5 polymorphic genes were assessed, this study likely underestimated the true genetic diversity in primary CMV infection.
When war hits home: Taiwanese public support for war of necessity
Authors: Yeh Yao-Yuan , Wu Charles K S
Published: October 2019

When a war directly intrudes citizens’ living space, it becomes a war of necessity for the public to defend themselves. However, current literature on public support for war has focused exclusively on wars of choice, not of necessity. Thus, we wonder if existing indicators of war support have explanatory power in this context. In this article, we examine existing indicators in a war of necessity—a cross-Strait conflict between Taiwan and China—to study how the public in Taiwan reacts. In addition to finding support for most of our hypotheses, the new context also contributes novel findings to the literature.
Transformational Post-Secularism: An Overlooked Strand of Thought
Authors: Schewel Benjamin
Published: October 2019

This article identifies an overlooked strand of post-secular thought, which I call “transformational.” Transformational post-secularism differs from other prominent post-secularisms by envisioning the emergence of a new socio-spiritual order that transcends modern secularism without abandoning its commitment to diversity. This article clarifies the main features of transformational post-secularism and identifies the historical context in which it arose. As part of this analysis, I argue that, contrary to Khaled Furani’s claim that post-secular discourse arose in the late 1990s, it actually began in the 1950s as part of a wider “crisis of man” debate. I also suggest that the axial age discourse, which crystallized at the same time and has gained significant influence in recent years, constitutes a main arena in which transformational post-secular thinking has, over the last seven decades, evolved. I conclude by considering the plausibility and potential applications of the idea of transformational post-secularism, which includes responding to Mahmood’s and Furani’s suggestion that scholars drop the term “post-secular” from their lexicon.
Helcococcus kunzii methyltransferase Erm(47) responsible for MLSB resistance is induced by diverse ribosome-targeting antibiotics
Authors: Guerin François , Rose Simon , Cattoir Vincent , Douthwaite Stephen
Published: October 2019

Objectives

To determine the mechanism of induction of erm(47) and its atypical expression in the Gram-positive opportunistic pathogen Helcococcus kunzii, where it confers resistance to a subset of clinically important macrolide, lincosamide and streptogramin B (MLSB) antibiotics.

Methods

The resistant H. kunzii clinical isolate UCN99 was challenged with subinhibitory concentrations of a wide range of ribosome-targeting drugs. The methylation status of the H. kunzii ribosomal RNA at the MLSB binding site was then determined using an MS approach and was correlated with any increase in resistance to the drugs.

Results

The H. kunzii erm(47) gene encodes a monomethyltransferase. Expression is induced by subinhibitory concentrations of the macrolide erythromycin, as is common for many erm genes, and surprisingly also by 16-membered macrolide, lincosamide, streptogramin, ketolide, chloramphenicol and linezolid antibiotics, all of which target the 50S ribosomal subunit. No induction was detected with spectinomycin, which targets the 30S subunit.

Conclusions

The structure of the erm(47) leader sequence functions as a hair trigger for the induction mechanism that expresses resistance. Consequently, translation of the erm(47) mRNA is tripped by MLSB compounds and also by drugs that target the 50S ribosomal subunit outside the MLSB site. Expression of erm(47) thus extends previous assumptions about how erm genes can be induced.
A bioactive extract from Olea europaea protects newly weaned beef heifers against experimentally induced chronic inflammation1
Authors: Cangiano Lautaro R , Zenobi Marcos G , Nelson Corwin D , Ipharraguerre Ignacio R , Dilorenzo Nicolas
Published: October 2019

Weaning is one of the most stressful periods in the life of a ruminant. Several factors entrenched within typical management practices pose challenges to the calf gastrointestinal health. Weaning is associated with losses in BW and feed intake. In addition, increasing highly fermentable carbohydrates in the diet at the expense of physically effective fiber after weaning predisposes the development of rumen acidosis and increases the concentration of endotoxin in rumen fluid and the permeability of the lower gut to luminal contents. Endotoxin translocation can elicit immune activation, shifting the metabolic priorities toward the immune system, which if sustained over time can hinder animal health and performance. Strategic supplementation of additives with anti-inflammatory capacity could represent a suitable approach to decrease systemic inflammation, restoring barrier function to luminal contents. Bioactive extracts from Olea europaea have anti-inflammatory activity and have been shown to reduce systemic inflammation in other animal models. A generalized randomized block design was used to evaluate the impact of feeding an olive oil bioactive extract (OBE) to newly weaned heifers injected intravenously with sequentially increasing doses of lipopolysaccharide (LPS). A total of 36 heifers, distributed across 3 experimental periods, were randomly assigned to 1 of 4 treatments that consisted of intravenous injection of either saline (CTL−) or with 6 sequentially increasing doses of LPS (0.10, 0.25, 0.50, 0.75, 1.00, and 1.25 µg/kg of BW) over a 10-d period (CTL+), and CTL+ plus dietary supplementation with a low (OBE-L; 0.04% of diet DM) or a high (OBE-H; 0.16% of diet DM) dose of OBE. Feeding OBE reduced some of the negative effects of prolonged immune activation with LPS, such as improved DMI and decreased intravaginal temperature in some, but not all of the days of LPS challenge (P < 0.05). In addition, feeding OBE reduced circulating concentration of inflammatory markers such as IL-6 and haptoglobin (P < 0.05). Heifers supplemented with OBE had reduced cell surface expression of the cluster of differentiation 14 (CD14) in monocyte cells (P < 0.01), a key receptor for LPS recognition, which was correlated with a faster recovery of immune cell counts in plasma. In conclusion, dietary supplementation with OBE was successful in mitigating the negative effects of sustained immune activation in newly weaned heifers.
Liver transcriptome profiling of beef steers with divergent growth rate, feed intake, or metabolic body weight phenotypes1
Authors: Mukiibi Robert , Vinsky Michael , Keogh Kate , Fitzsimmons Carolyn , Stothard Paul , Waters Sinéad M , Li Changxi
Published: October 2019

Average daily gain (ADG) and daily dry matter intake (DMI) are key determinants of beef industry profitability. These traits together with metabolic body weight (MWT) are combined as component traits to calculate residual feed intake (RFI), a common measure of feed efficiency in beef cattle. Recently, there have been significant efforts towards molecular genetic characterization of RFI through transcriptomic studies in different breeds and tissues. However, molecular mechanisms of RFI component traits still remain predominately unexplored. Therefore, in the current study, we investigated the hepatic transcriptomic profiles and their associations with ADG, DMI, and MWT in Angus, Charolais, and Kinsella Composite (KC) populations through global RNAseq analyses. In each population and for each trait, 12 steers with extreme phenotypes (n = 6 low and n = 6 high) were analyzed for differential gene expression. These animals were from 20 beef steers of each Angus, Charolais, and KC breed population that were initially selected for a transcriptome study of RFI. At a false discovery rate <0.05 and fold change >1.5, we identified 123, 102, and 78 differentially expressed (DE) genes between high- and low-ADG animals of Angus, Charolais, and KC populations, respectively. For DMI, 108, 180, and 156 DE genes were identified between high- and low-DMI from Angus, Charolais, and KC populations, respectively, while for MWT, 80, 82, and 84 genes were differentially expressed between high- and low-MWT animals in Angus, Charolais, and KC populations, respectively. The identified DE genes were largely breed specific (81.7% for ADG, 82.7% for DMI, and 83% for MWT), but were largely involved in the same biological functions across the breeds. Among the most enriched biological functions included metabolism of major nutrients (lipids, carbohydrates, amino acids, vitamins, and minerals), small molecule biochemistry, cellular movement, cell morphology, and cell-to-cell signaling and interaction. Notably, we identified multiple DE genes that are involved in cholesterol biosynthesis, and immune response pathways for the 3 studied traits. Thus, our findings present potential molecular genetic mechanisms and candidate genes that influence feed intake, growth, and MWT of beef cattle.
Hypermetabolism of glutathione, glutamate and ornithine via redox imbalance in methylglyoxal-induced peritoneal injury rats
Authors: Hirahara Ichiro , Kusano Eiji , Jin Denan , Takai Shinji
Published: October 2019

Peritoneal dialysis (PD) is a blood purification treatment for patients with reduced renal function. However, the peritoneum is exposed to oxidative stress during PD and long-term PD results in peritoneal damage, leading to the termination of PD. Methylglyoxal (MGO) contained in commercial PD fluids is a source of strong oxidative stress. The aim of this study was to clarify the mechanism of MGO-induced peritoneal injury using metabolome analysis in rats. We prepared peritoneal fibrosis rats by intraperitoneal administration of PD fluids containing MGO for 21 days. As a result, MGO-induced excessive proliferation of mesenchymal cells with an accumulation of advanced glycation end-products (AGEs) at the surface of the thickened peritoneum in rats. The effluent levels of methionine sulfoxide, an oxidative stress marker and glutathione peroxidase activity were increased in the MGO-treated rats. The levels of glutathione, glutamate, aspartate, ornithine and AGEs were also increased in these rats. MGO upregulated the gene expression of transporters and enzymes related to the metabolism of glutathione, glutamate and ornithine in the peritoneum. These results suggest that MGO may induce peritoneal injury with mesenchymal cell proliferation via increased redox metabolism, directly or through the formation of AGEs during PD.
As the Wind Blows: The Effects of Long-Term Exposure to Air Pollution on Mortality
Authors: Anderson Michael L
Published: October 2019

There is strong evidence that short-run fluctuations in air pollution negatively impact infant health and contemporaneous adult health, but there is less evidence on the causal link between long-term exposure to air pollution and increased adult mortality. This project estimates the impact of long-term exposure to air pollution on mortality by leveraging quasi-random variation in pollution levels generated by wind patterns near major highways. I combine geocoded data on the residence of every decedent in Los Angeles over three years, high-frequency wind data, and Census short form data. Using these data, I estimate the effect of downwind exposure to highway-generated pollutants on the age-specific mortality rate by using orientation to the nearest major highway as an instrument for pollution exposure. I find that doubling the percentage of time spent downwind of a highway increases mortality among individuals 75 or older by 3.8%–6.5%. These estimates are robust and imply significant loss of life years.
An Exploratory Association Analysis of the Insulin Gene Region With Diabetes Mellitus in Two Dog Breeds
Authors: Hess Rebecka , Henthorn Paula , Devoto Marcella , Wang Fan , Feng Rui
Published: October 2019

Samoyeds and Australian Terriers are the 2 dog breeds at highest risk (>10-fold) for diabetes mellitus in the United States. It is unknown if the insulin (INS) gene is involved in the pathophysiology of diabetes in Samoyeds and Australian Terriers. It was hypothesized that the INS gene region provides a common genetic causality for diabetes in Samoyeds and Australian Terriers. We conducted a 2-stage genetic association study involving both breeds. In the discovery stage (Stage 1), Samoyeds with and without diabetes were compared in the frequencies of 447 tagging single-nucleotide polymorphisms (SNPs) within 2.5 megabases (Mb) up- and downstream of the INS gene on the Illumina CanineHD BeadChip. SNPs yielding a P-value < 0.005 were selected for further follow-up. In the validation stage (Stage 2), Australian Terriers with and without diabetes were compared in the SNPs genotyped by the Affymetrix GeneChip Canine Genome 2.0 Array and within 1 Mb up- and downstream of the selected SNPs from Stage 1. Two SNPs that were in high linkage disequilibrium (LD, r2 = 0.7) were selected from Stage 1. In Stage 2, among the 76 SNPs examined, 5 were significantly associated with diabetes after Bonferroni’s correction for multiple comparisons. Three of these 5 SNPs were in complete LD (r2 = 1 for all associations) and the 2 remaining SNPs were in moderate LD (r2 = 0.4). In conclusion, an association between the INS gene region and diabetes was suggested in 2 dog breeds of different clades. This region could have importance in diabetes in other breeds or in canine diabetes at large.
Ethical Issues in Physician Billing Under Fee-For-Service Plans
Authors: Heath Joseph
Published: October 2019

Medical ethics has become an important and recognized component of physician training. There is one area, however, in which medical students receive little guidance. There is practically no discussion of the financial aspects of medical practice. My objective in this paper is to initiate a discussion about the moral dimension of physician billing practices. I argue that physicians should expand their conception of professional responsibility in order to recognize that their moral obligations toward patients include a commitment to honest and forthright billing practices. I argue that physicians should aspire to a standard of clinical accuracy—not legal adequacy—in describing their activities. More generally, physicians should strive to promote an integrity-based professional culture, first and foremost by stigmatizing rather than celebrating creative billing practices, as well as condemning the misguided sense of solidarity that currently makes it taboo for physicians to criticize each other on this score.
Employment Changes Following Breast Cancer Diagnosis: The Effects of Race and Place
Authors: Spencer Jennifer C , Rotter Jason S , Eberth Jan M , Zahnd Whitney E , Vanderpool Robin C , Ko Linda K , Davis Melinda M , Troester Melissa A , Olshan Andrew F , Wheeler Stephanie B
Published: October 2019

The financial implications of breast cancer diagnosis may be greater among rural and black women. Women with incident breast cancer were recruited as part of the Carolina Breast Cancer Study. We compared unadjusted and adjusted prevalence of cancer-related job or income loss, and a composite measure of either outcome, by rural residence and stratified by race. We included 2435 women: 11.7% were rural; 48.5% were black; and 38.0% reported employment changes after diagnosis. Rural women more often reported employment effects, including reduced household income (43.6% vs 35.4%, two-sided χ2 test P = .04). Rural white, rural black, and urban black women each more often reported income reduction (statistically significant vs. urban white women), although these groups did not meaningfully differ from each other. In multivariable regression, rural differences were mediated by socioeconomic factors, but racial differences remained. Programs and policies to reduce financial toxicity in vulnerable patients should address indirect costs of cancer, including lost wages and employment.
The Sexual Harassment of Federal Employees: Gender, Leadership Status, and Organizational Tolerance for Abuses of Power
Authors: Tinkler Justine E , Zhao Jun
Published: October 2019

Theory and research suggest that sexual harassment is often a dominance strategy used to undermine women’s power, but the precise relationships between government employees’ workplace power, organizational climate, and vulnerability to particular types of sexual harassment remain under-specified. This study analyzes data from the 2016 US Merit Systems Protection Board survey of the federal civilian workforce (the most comprehensive and up-to-date national data on workplace sexual harassment) to test predictions about how employees’ workplace power and their agency’s efforts to mitigate abuses of power affect their likelihood of experiencing sexual harassment. Findings reveal that women in leadership positions report more sexual harassment than non-leaders, and that team leaders (i.e., those without formal supervisory authority) and executives (i.e., those with the most authority) report more sexual harassment than women in middle management. At the organizational level, sexual harassment occurs in workplaces with higher levels of non-sexual aggression and among employees who perceive their agency as less proactive in preventing and responding to social inequity. Taken together, findings suggest that sexual harassment is a dominance strategy not unlike other forms of aggression used to undermine women in power, and that workplace climates that are effective at mitigating abuses of power reduce the likelihood of experiencing sexual harassment. These results have implications for how government agencies can implement policies that not only prevent harassment but also promote democracy and equity among an increasingly diverse federal workforce.
The plant-specific ABERRANT GAMETOGENESIS 1 gene is essential for meiosis in rice
Authors: Chang Zhenyi , Xu Chunjue , Huang Xiaoyan , Yan Wei , Qiu Shijun , Yuan Shuting , Ni Haoling , Chen Shujing , Xie Gang , Chen Zhufeng , Wu Jianxin , Tang Xiaoyan
Published: October 2019

Meiotic recombination plays a central role in maintaining genome stability and increasing genetic diversity. Although meiotic progression and core components are widely conserved across kingdoms, significant differences remain among species. Here we identify a rice gene ABERRANT GAMETOGENESIS 1 (AGG1) that controls both male and female gametogenesis. Cytological and immunostaining analysis showed that in the osagg1 mutant the early recombination processes and synapsis occurred normally, but the chiasma number was dramatically reduced. Moreover, OsAGG1 was found to interact with ZMM proteins OsHEI10, OsZIP4, and OsMSH5. These results suggested that OsAGG1 plays an important role in crossover formation. Phylogenetic analysis showed that OsAGG1 is a plant-specific protein with a highly conserved N-terminal region. Further genetic and protein interaction analyses revealed that the conserved N-terminus was essential for the function of the OsAGG1 protein. Overall, our work demonstrates that OsAGG1 is a novel and critical component in rice meiotic crossover formation, expanding our understanding of meiotic progression.

This study identified a plant-specific gene ABERRANT GAMETOGENESIS 1 that is required for meiotic crossover formation in rice. The conserved N-terminus of the AGG1 protein was found to be essential for its function.
Arabidopsis cyclic nucleotide-gated channel 6 is negatively modulated by multiple calmodulin isoforms during heat shock
Authors: Niu Wei-Tao , Han Xiao-Wei , Wei Shan-Shan , Shang Zhong-Lin , Wang Jing , Yang De-Wei , Fan Xiao , Gao Fei , Zheng Shu-Zhi , Bai Jiao-Teng , Zhang Bo , Wang Zi-Xuan , Li Bing
Published: October 2019

Arabidopsis calmodulin isoforms CaM2/3/5 and CaM7 negatively regulate Ca2+ conductivity during heat shock by binding to an atypical IQ motif in cyclic nucleotide-gated ion channel 6.
Approaches to improve soil fertility in sub-Saharan Africa
Authors: Stewart Zachary P , Pierzynski Gary M , Middendorf B Jan , Prasad P V Vara
Published: October 2019

Soil fertility provides the foundation for nutritious food production and resilient and sustainable livelihoods. A comprehensive survey and summit meeting were conducted with the aims of understanding barriers to enhancing soil fertility in sub-Saharan Africa and providing evidence-based recommendations. The focus regions were West Africa, East Africa, the Great Lakes region, and Ethiopia. Overall recommendations were developed with four emerging themes: (1) strengthening inorganic fertilizer-based systems, (2) access to and use of quality organic inputs, (3) capacity building along the entire knowledge-transfer value chain, and (4) strengthening farming systems research and development across biophysical and socio-economic factors. The evidence-based process and methodology for prioritizing these recommendations makes these findings useful for setting out action plans for future investments and strategies. Access to inorganic fertilizer, its use, and related implementation issues were prominent considerations; nevertheless, biophysical and socio-economic barriers and solutions were identified as equally important to building soil fertility and natural resources. Soil management initiatives should focus on providing holistic solutions covering both biophysical and socio-economic aspects along the entire value chain of actors and creating an enabling environment for adoption. A broader view of soil fertility improvement using all available options including both inorganic and organic sources of nutrients and farming system approaches are highly recommended.
‘Keeping busy with purpose’: How meaningful occupation can shape the experience of forced migration
Authors: Hart Helen Claire
Published: October 2019

Forced migration creates multiple barriers to everyday life, including individual’s access to dignified and meaningful daily occupations. Without the activities that form family life, self-care, work, leisure, and community participation, individuals can find themselves struggling to fill the hours in their days and feeling they exist on the margins of society. This article reflects the findings of a small-scale phenomenological study exploring the meaning of everyday occupations to people seeking asylum in the UK. A series of in-depth interviews, conducted with 10 people, explored the role of daily occupation in their country of origin and in the UK. The study found that restrictions on daily activities had a significant impact on their well-being and sense of self-worth. They highlighted how limited their opportunities were and acknowledged the value of meaningful daily occupations as a means to ‘keep busy with purpose’. There is growing evidence that occupation has the potential to be of benefit to people during the post-migratory period: maintaining health, preserving key skills, retaining a sense of self, and increasing integration. This study shows the multiple gains associated with purposeful activity, including how the right kind of occupation can promote self-worth at a time when people often feel devalued. The article encourages the reader to consider how increased access to activity can promote well-being and to consider challenging the occupational injustices behind asylum policy.
Why Be Random?
Authors: Icard Thomas
Published: October 2019

When does it make sense to act randomly? A persuasive argument from Bayesian decision theory legitimizes randomization essentially only in tie-breaking situations. Rational behaviour in humans, non-human animals, and artificial agents, however, often seems indeterminate, even random. Moreover, rationales for randomized acts have been offered in a number of disciplines, including game theory, experimental design, and machine learning. A common way of accommodating some of these observations is by appeal to a decision-maker’s bounded computational resources. Making this suggestion both precise and compelling is surprisingly difficult. Toward this end, I propose two fundamental rationales for randomization, drawing upon diverse ideas and results from the wider theory of computation. The first unifies common intuitions in favour of randomization from the aforementioned disciplines. The second introduces a deep connection between randomization and memory: access to a randomizing device is provably helpful for an agent burdened with a finite memory. Aside from fit with ordinary intuitions about rational action, the two rationales also make sense of empirical observations in the biological world. Indeed, random behaviour emerges more or less where it should, according to the proposal.
Loss of Imprinting in Human Placentas Is Widespread, Coordinated, and Predicts Birth Phenotypes
Authors: Vincenz Claudius , Lovett Jennie L , Wu Weisheng , Shedden Kerby , Strassmann Beverly I
Published: October 2019

Genomic imprinting leads to mono-allelic expression of genes based on parent of origin. Therian mammals and angiosperms evolved this mechanism in nutritive tissues, the placenta, and endosperm, where maternal and paternal genomes are in conflict with respect to resource allocation. We used RNA-seq to analyze allelic bias in the expression of 91 known imprinted genes in term human placentas from a prospective cohort study in Mali. A large fraction of the imprinted exons (39%) deviated from mono-allelic expression. Loss of imprinting (LOI) occurred in genes with either maternal or paternal expression bias, albeit more frequently in the former. We characterized LOI using binomial generalized linear mixed models. Variation in LOI was predominantly at the gene as opposed to the exon level, consistent with a single promoter driving the expression of most exons in a gene. Some genes were less prone to LOI than others, particularly lncRNA genes were rarely expressed from the repressed allele. Further, some individuals had more LOI than others and, within a person, the expression bias of maternally and paternally imprinted genes was correlated. We hypothesize that trans-acting maternal effect genes mediate correlated LOI and provide the mother with an additional lever to control fetal growth by extending her influence to LOI of the paternally imprinted genes. Limited evidence exists to support associations between LOI and offspring phenotypes. We show that birth length and placental weight were associated with allelic bias, making this the first comprehensive report of an association between LOI and a birth phenotype.
Lasiurus varius (Chiroptera: Vespertilionidae)
Authors: Ossa Gonzalo , Díaz M Mónica , Barquez Rubén M
Published: October 2019

Lasiurus varius (Poeppig, 1835) is a vespertilionid bat commonly known as Chilean red bat or cinnamon red bat. L. varius is characterized by its deep reddish coloration without frosted appearance, and by the uropatagium covered with long hairs that extend beyond the trailing edge, which clearly distinguishes it from the other species in the genus. The distribution of this rare species is restricted to the southern parts of Argentina and Chile.
Ribosome assembly defects subvert initiation Factor3 mediated scrutiny of bona fide start signal
Authors: Sharma Himanshu , Anand B
Published: October 2019

In bacteria, the assembly factors tightly orchestrate the maturation of ribosomes whose competency for protein synthesis is validated by translation machinery at various stages of translation cycle. However, what transpires to the quality control measures when the ribosomes are produced with assembly defects remains enigmatic. In Escherichia coli, we show that 30S ribosomes that harbour assembly defects due to the lack of assembly factors such as RbfA and KsgA display suboptimal initiation codon recognition and bypass the critical codon–anticodon proofreading steps during translation initiation. These premature ribosomes on entering the translation cycle compromise the fidelity of decoding that gives rise to errors during initiation and elongation. We show that the assembly defects compromise the binding of initiation factor 3 (IF3), which in turn appears to license the rapid transition of 30S (pre) initiation complex to 70S initiation complex by tempering the validation of codon–anticodon interaction during translation initiation. This suggests that the premature ribosomes harbouring the assembly defects subvert the IF3 mediated proofreading of cognate initiation codon to enter the translation cycle.
Direct sequencing of RNA with MinION Nanopore: detecting mutations based on associations
Authors: Harel Noam , Meir Moran , Gophna Uri , Stern Adi
Published: October 2019

One of the key challenges in the field of genetics is the inference of haplotypes from next generation sequencing data. The MinION Oxford Nanopore sequencer allows sequencing long reads, with the potential of sequencing complete genes, and even complete genomes of viruses, in individual reads. However, MinION suffers from high error rates, rendering the detection of true variants difficult. Here, we propose a new statistical approach named AssociVar, which differentiates between true mutations and sequencing errors from direct RNA/DNA sequencing using MinION. Our strategy relies on the assumption that sequencing errors will be dispersed randomly along sequencing reads, and hence will not be associated with each other, whereas real mutations will display a non-random pattern of association with other mutations. We demonstrate our approach using direct RNA sequencing data from evolved populations of the MS2 bacteriophage, whose small genome makes it ideal for MinION sequencing. AssociVar inferred several mutations in the phage genome, which were corroborated using parallel Illumina sequencing. This allowed us to reconstruct full genome viral haplotypes constituting different strains that were present in the sample. Our approach is applicable to long read sequencing data from any organism for accurate detection of bona fide mutations and inter-strain polymorphisms.
The Association of Preoperative Opioid Usage With Patient-Reported Outcomes, Adverse Events, and Return to Work After Lumbar Fusion: Analysis From the Michigan Spine Surgery Improvement Collaborative (MSSIC)
Authors: Zakaria Hesham Mostafa , Mansour Tarek R , Telemi Edvin , Asmaro Karam , Bazydlo Michael , Schultz Lonni , Nerenz David R , Abdulhak Muwaffak , Khalil Jad G , Easton Richard , Schwalb Jason M , Park Paul , Chang Victor
Published: October 2019

BACKGROUND

It is important to delineate the relationship between opioid use and spine surgery outcomes.

OBJECTIVE

To determine the association between preoperative opioid usage and postoperative adverse events, patient satisfaction, return to work, and improvement in Oswestry Disability Index (ODI) in patients undergoing lumbar fusion procedures by using 2-yr data from a prospective spine registry.

METHODS

Preoperative opioid chronicity from 8693 lumbar fusion patients was defined as opioid-naïve (no usage), new users (<6 wk), short-term users (6 wk-3 mo), intermediate-term users (3-6 mo), and chronic users (>6 mo). Multivariate generalized estimating equation models were constructed.

RESULTS

All comparisons were to opioid-naïve patients. Chronic opioid users showed less satisfaction with their procedure at 90 d (Relative Risk (RR) 0.95, P = .001), 1 yr (RR 0.89, P = .001), and 2 yr (RR 0.89, P = .005). New opioid users were more likely to show improvement in ODI at 90 d (RR 1.25, P < .001), 1 yr (RR 1.17, P < .001), and 2 yr (RR 1.19, P = .002). Short-term opioid users were more likely to show ODI improvement at 90 d (RR 1.25, P < .001). Chronic opioid users were less likely to show ODI improvement at 90 d (RR 0.90, P = .004), 1 yr (RR 0.85, P < .001), and 2 yr (RR 0.80, P = .003). Chronic opioid users were less likely to return to work at 90 d (RR 0.80, P < .001).

CONCLUSION

In lumbar fusion patients and when compared to opioid-naïve patients, new opioid users were more likely and chronic opioid users less likely to have improved ODI scores 2 yr after surgery. Chronic opioid users are less likely to be satisfied with their procedure 2 yr after surgery and less likely to return to work at 90 d. Preoperative opioid counseling is advised.
Thrombectomy in DAWN- and DEFUSE-3-Ineligible Patients: A Subgroup Analysis From the BEST Prospective Cohort Study
Authors: Siegler James E , Messé Steven R , Sucharew Heidi , Kasner Scott E , Mehta Tapan , Arora Niraj , Starosciak Amy K , De Los Rios La Rosa Felipe , Barnhill Natasha R , Mistry Akshitkumar M , Patel Kishan , Assad Salman , Tarboosh Amjad , Dakay Katarina , Salwi Sanjana , Wagner Jeff , Bennett Alicia , Jagadeesan Bharathi D , Streib Christopher , Weber Stewart A , Chitale Rohan , Volpi John J , Mayer Stephan A , Yaghi Shadi , Jayaraman Mahesh , Khatri Pooja , Mistry Eva A
Published: October 2019

BACKGROUND

Because of the overwhelming benefit of thrombectomy for highly selected trial patients with large vessel occlusion (LVO), some trial-ineligible patients are being treated in practice.

OBJECTIVE

To determine the safety and efficacy of thrombectomy in DAWN/DEFUSE-3-ineligible patients.

METHODS

Using a multicenter prospective observational study of consecutive patients with anterior circulation LVO who underwent late thrombectomy, we compared symptomatic intracerebral hemorrhage (sICH) and good outcome (90-d mRS 0-2) among DAWN/DEFUSE-3-ineligible patients to trial-eligible patients and to untreated DAWN/DEFUSE-3 controls.

RESULTS

Ninety-eight patients had perfusion imaging and underwent thrombectomy >6 h; 46 (47%) were trial ineligible (41% M2 occlusions, 39% mild deficits, 28% ASPECTS <6). In multivariable regression, the odds of a good outcome (aOR 0.76, 95% CI 0.49-1.19) and sICH (aOR 3.33, 95% CI 0.42-26.12) were not different among trial-ineligible vs eligible patients. Patients with mild deficits were more likely to achieve a good outcome (aOR 3.62, 95% CI 1.48-8.86) and less sICH (0% vs 10%, P = .16), whereas patients with ASPECTS <6 had poorer outcomes (aOR 0.14, 95% CI 0.05-0.44) and more sICH (aOR 24, 95% CI 5.7-103). Compared to untreated DAWN/DEFUSE-3 controls, trial-ineligible patients had more sICH (13%BEST vs 3%DAWN [P = .02] vs 4%DEFUSE [P = .05]), but were more likely to achieve a good outcome at 90 d (36%BEST vs 13%DAWN [P < .01] vs 17%DEFUSE [P = .01]).

CONCLUSION

Thrombectomy is used in practice for some patients ineligible for the DAWN/DEFUSE-3 trials with potentially favorable outcomes. Additional trials are needed to confirm the safety and efficacy of thrombectomy in broader populations, such as large core infarction and M2 occlusions.
Blood Culture–Negative Cardiovascular Infection in a Patient With Multiple Sclerosis
Authors: Melenotte Cléa , Loukil Ahmed , Rico Audrey , Lepidi Hubert , Raoult Didier
Published: October 2019

A patient with multiple sclerosis presented with seronegative C. burnetii endocarditis diagnosed using C. burnetii–specific polymerase chain reaction and fluorescence in situ hybridization on cardiovascular biopsy. This case supports the necessity of a systematic polymerase chain reaction testing of removed cardiac valves because blood culture–negative endocarditis can be pauci-symptomatic, and serological tests can be negative in cases of immunosuppression.
Development of a Comprehensive, Nonsurgical Joint Health Program for People With Osteoarthritis: A Case Report
Authors: Malay Morven R , Lentz Trevor A , O’Donnell Jonathan , Coles Theresa , Mather III Richard Chad , Jiranek William A
Published: October 2019

Background and Purpose

Existing osteoarthritis (OA) care models often fall short in addressing the many biological, psychological, social, and behavioral characteristics that contribute to disability. As US health care shifts towards value-based payment, there is an increasing need to develop and test scalable, cost-effective, and multi-modal OA care models. This administrative case report will describe the development and pilot of a new, value-based comprehensive care model for OA.

Case Description

The Joint Health Program (JHP) is a physical therapist-led conservative care model for individuals with hip and knee OA. In the JHP, physical therapists with specialized training in cognitive behavioral-theory based strategy function as the central care provider (ie, the primary osteoarthritis provider) who delivers evidence-based, psychologically informed interventions and coordinates care within a multi-disciplinary network of dietitians, behavioral health specialists, and orthopedic providers. The JHP is focused on enhancing patient engagement, shared decision making, self-management and multi-modal patient interaction, and long-term follow-up.

Outcomes

A value-based, comprehensive care program for OA led by physical therapists demonstrated feasibility and acceptability within a large, academic health care system, which has led to its early growth. Barriers to development and integration of the program were addressed through effective collaboration among health care providers, program and health system administrators, and executive leadership.

Discussion

The JHP serves as a model for future physical therapist-led, value-based care models that could be developed in other health care systems for OA and other chronic conditions. Future work will identify characteristics that predict program response and compare the effectiveness of this program to existing models of care.
A double-blind, placebo-controlled, phase II, randomized study of lovastatin therapy in the treatment of mildly active rheumatoid arthritis
Authors: Aranow Cynthia , Cush John , Bolster Marcy B , Striebich Christopher C , Dall’era Maria , Mackay Meggan , Olech Ewa , Frech Tracy , Box Jane , Keating Richard , Wasko Mary Chester , St Clair William , Kivitz Alan , Huang Weiquang , Ricketts PetaGay , Welch Beverly , Callahan Sherrie , Spychala Meagan , Boyle Karen , York Kate , Keyes-Elstein Lynette , Goldmuntz Ellen , Diamond Betty , Davidson Anne
Published: October 2019

Objectives

3-hydroxy-3-methylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors (statins) are standard treatment for hyperlipidaemia. In addition to lipid-lowering abilities, statins exhibit multiple anti-inflammatory effects. The objectives of this study were to determine whether treatment of patients with RA with lovastatin decreased CRP or reduced disease activity.

Methods

We conducted a randomized double-blind placebo-controlled 12 week trial of lovastatin vs placebo in 64 RA patients with mild clinical disease activity but an elevated CRP. The primary efficacy end point was the reduction in mean log CRP. Secondary end points included disease activity, RF and anti–CCP antibody titres. Mechanistic end points included levels of serum cytokines. Safety was assessed; hepatic and muscle toxicities were of particular interest.

Results

Baseline features were similar between groups. No significant difference in mean log CRP reduction between the two groups was observed, and disease activity did not change from baseline in either treatment group. Mechanistic analyses did not reveal significant changes in any biomarkers. A post hoc analysis of subjects not using biologic therapy demonstrated a significantly greater proportion achieving ⩾20% reduction in CRP from baseline in the lovastatin group compared with placebo (P-value = 0.007). No difference was observed in subjects receiving biologics. Lovastatin was well tolerated with no serious safety concerns.

Conclusion

This study showed no anti-inflammatory or clinical effects on RA disease activity after 12 weeks of treatment with lovastatin. Lovastatin had a modest effect on CRP in subjects not using biologics, suggesting statins may be anti-inflammatory in selected patients.

Trial registration

ClinicalTrials.gov, http://clinicaltrials.gov, NCT00302952.
Comorbid fibromyalgia impairs the effectiveness of biologic drugs in patients with psoriatic arthritis
Authors: Iannone Florenzo , Nivuori Mariangela , Fornaro Marco , Venerito Vincenzo , Cacciapaglia Fabio , Lopalco Giuseppe
Published: October 2019

Objectives

To evaluate the impact of FM on the clinical outcomes of biologics in patients with PsA in real life.

Methods

FM was diagnosed according to current criteria among PsA patients starting a first biologic drug from 2010 through 2017. At each visit, disease activity of PsA (DAPSA), minimal disease activity (MDA), HAQ, rate of patients achieving DAPSA-based low disease activity (LDA) or remission, and MDA were evaluated. Lost patients or those not achieving the target were imputed as non-responders. The drug survival was evaluated by Kaplan–Meyer analysis. Estimated hazard ratios (HRs) of discontinuing therapy or achieving MDA were assessed by multivariate regression models.

Results

A total of 238 patients, of whom 58 had also FM, started a first biologic drug. Compared with no-FM PsA, FM PsA patients were more frequently female (P = 0.0001) with polyarticular subset (P = 0.0001), and with higher mean BMI (P = 0.006). Drug survival was significantly lower in FM PsA (50%, mean 32 months) than in no-FM PsA (74%, mean 42 months, P = 0.0001). Rates of remission/LDA and MDA were significantly lower in FM PsA at 3, 6, 12 and 24 months (P < 0.001). Remission in FM PsA was negligible (3.4% and 0% at 3 and 6 months, respectively). Negative predictors of drug discontinuation were no FM (HR 0.51) and normal weight (HR 0.29), while no FM (HR 2.54) and male sex (HR 1.58) were positive predictors of long-standing MDA.

Conclusions

Comorbid FM, along with female gender and obesity seem to be the worst combination of negative prognostic factors in PsA.
IMPROVEMENT OF GAMMA-RAY SUBTRACTION PROCEDURE FOR A CURRENT-MODE NEUTRON DETECTOR WITH A PAIR OF 6Li- AND 7Li-GLASS SCINTILLATORS
Authors: Matsumoto Tetsuro , Masuda Akihiko , Harano Hideki , Hori Jun-ichi , Sano Tadafumi
Published: October 2019

A current-mode neutron detector with a pair of 6Li- and 7Li-glass scintillators has been developed to measure high-flux neutrons in a boron neutron capture therapy field. Neutrons are basically measured by subtracting gamma-ray component using current outputs from the 7Li-glass scintillator. In the present study, the difference in the gamma-ray sensitivity between the 6Li- and 7Li-glass scintillators and the neutron sensitivity for the 7Li-glass scintillator due to the 6Li contamination were also considered to improve the gamma-ray subtraction precision. The gamma-ray subtraction procedure was experimentally investigated in thermal neutron fields with 252Cf and 241Am-Be neutron sources, which have different gamma-ray intensities per unit neutron fluence. A linear relation between neutron fluence and current output was obtained for the neutron detector in the two types of thermal neutron fields with different gamma-ray intensities. It was found that the gamma-ray subtraction procedure is useful for current-mode neutron detectors.