bluuebunny/crossref_metadata_2025 huggingface dataset:
Declines in Depressive Symptoms Among People who Inject Drugs Treated With Direct-Acting Antivirals While on Opioid Agonist Therapy
Authors: Pericot-Valverde Irene , Heo Moonseong , Niu Jiajing , Norton Brianna L , Akiyama Matthew J , Agyemang Linda , Litwin Alain H
Published: October 2020

Background

Hepatitis C virus (HCV) frequently co-occurs with symptoms of depression, which are aggravated on interferon-based regimens. However, it is unknown whether HCV treatment with direct-acting antivirals (DAAs) has effects on depressive symptoms among people who inject drugs (PWID). In this study, we examined changes in depressive symptoms during and after HCV treatment among PWID on opioid agonist therapies (OATs).

Methods

Participants were 141 PWID who achieved sustained viral response after on-site HCV treatment at 3 OAT programs.

Depressive symptoms were assessed using the Beck Depression Inventory–II (BDI-II) at baseline, every 4 weeks during treatment, and 12 and 24 weeks after treatment completion. Current diagnosis of depression or other psychiatric diagnoses were obtained through chart review. Use of illicit drugs was measured by urine toxicology screening. Alcohol use was measured using the Addiction Severity Index–Lite.

Results

Of the 141 PWID infected with HCV, 24.1% had severe, 9.9% had moderate, 15.6% had mild, and 50.4% had minimal levels of depression as per BDI-II scores at baseline. HCV treatment was significantly associated with reductions in depressive symptoms that persisted long term, regardless of symptom severity (P < .001) or presence of depression (P ≤ .01) or other psychiatric diagnoses (P ≤ .01) at baseline. Concurrent drug use (P ≤ .001) or hazardous alcohol drinking (P ≤ .001) did not interfere with reductions in depressive symptoms.

Conclusions

Depressive symptoms are highly prevalent among HCV-infected PWID. HCV treatment was associated with sustained reductions in depressive symptoms. HCV therapy with DAAs may have important implications for PWID that go beyond HCV cure.
Cutaneous Leishmaniasis: Case Series on Pregnancy Outcome
Authors: Bitton Yossi , Diav-Citrin Orna
Published: October 2020

We report the pregnancy outcomes of 6 women with cutaneous leishmaniasis; 5 of these women received topical antileishmenial therapy during gestation with paromomycin plus methylbenzethonium chloride combination ointment and/or sodium stibogluconate intralesional injections. No teratogenic effects were reported. Furthermore, no vertical transmission was observed.
Do generous parental leave policies help top female earners?
Authors: Corekcioglu Gozde , Francesconi Marco , Kunze Astrid
Published: October 2020

Generous government-mandated parental leave is generally viewed as an effective policy to support women’s careers around childbirth. But does it help women to reach top positions in the upper pay echelon of their firms? Using longitudinal employer–employee matched data for the entire Norwegian population, we address this question exploiting a series of reforms that expanded paid leave from 30 weeks in 1989 to 52 weeks in 1993. The representation of women in top positions has only moderately increased over time, and career profiles of female top earners within firms are significantly different from those of their male counterparts. The reforms did not affect, and possibly decreased, the probability for women to be at the top over their life cycle. We discuss some implications of this result to put into perspective the design of new family-friendly policy interventions.
Octaketide Synthase from Polygonum cuspidatum Implements Emodin Biosynthesis in Arabidopsis thaliana
Authors: Guo Yanwu , Nassar Sara , Ma Lanqing , Feng Guanping , Li Xing , Chen Mo , Chai Tuanyao , Abdel-Rahman Iman A M , Beuerle Till , Beerhues Ludger , Wang Hong , Liu Benye
Published: October 2020

Plant anthranoids are medicinally used for their purgative properties. Their scaffold was believed to be formed by octaketide synthase (OKS), a member of the superfamily of type III polyketide synthase (PKS) enzymes. Here, a cDNA encoding OKS of Polygonum cuspidatum was isolated using a homology-based cloning strategy. When produced in Escherichia coli, P. cuspidatum octaketide synthase (PcOKS) catalyzed the condensation of eight molecules of malonyl-CoA to yield a mixture of unphysiologically folded aromatic octaketides. However, when the ORF for PcOKS was expressed in Arabidopsis thaliana, the anthranoid emodin was detected in the roots of transgenic lines. No emodin was found in the roots of wild-type A. thaliana. This result indicated that OKS is the key enzyme of plant anthranoids biosynthesis. In addition, the root growth of the transgenic A. thaliana lines was inhibited to an extent that resembled the inhibitory effect of exogenous emodin on the root growth of wild-type A. thaliana. Immunochemical studies of P. cuspidatum plants detected PcOKS mainly in roots and rhizome, in which anthranoids accumulate. Co-incubation of E. coli - produced PcOKS and cell-free extract of wild-type A. thaliana roots did not form a new product, suggesting an alternative, physiological folding of PcOKS and its possible interaction with additional factors needed for anthranoids assembling in transgenic A. thaliana. Thus, transgenic A. thaliana plants producing PcOKS provide an interesting system for elucidating the route of plant anthranoid biosynthesis.
The Combination of Preoperative Pain, Conditioned Pain Modulation, and Pain Catastrophizing Predicts Postoperative Pain 12 Months After Total Knee Arthroplasty
Authors: Larsen Dennis Boye , Laursen Mogens , Edwards Robert R , Simonsen Ole , Arendt-Nielsen Lars , Petersen Kristian Kjær
Published: October 2020

Objectives

Approximately 20% of knee osteoarthritis patients undergoing total knee arthroplasty (TKA) report chronic postoperative pain. Studies suggest that preoperative variables such as impaired descending pain control, catastrophizing, function, and neuropathic pain–like symptoms may predict postoperative pain 12 months after TKA, but the combined prediction value of these factors has not been tested. The current prospective cohort study aimed to combine preoperative risk factors to investigate the predictive value for postoperative pain 12 months after TKA.

Design

Prospective cohort with follow-up 12 months after surgery.

Patients

A consecutive sample of 131 knee osteoarthritis patients undergoing TKA.

Methods

Pain intensity, Pain Catastrophizing Scale (PCS) scores, PainDETECT Questionnaire scores, conditioned pain modulation (CPM), and Oxford Knee Score (OKS) were obtained before and 12 months after TKA.

Results

TKA improved pain (P < 0.001), PCS scores (P < 0.001), PainDETECT Questionnaire scores (P < 0.001), and OKSs (P < 0.001). Preoperative pain correlated with preoperative PCS scores (r = 0.38, P  <  0.001), PainDETECT scores (r = 0.53, P  <  0.001), and OKSs (r = –0.25, P  =  0.001). Preoperative PainDETECT scores were associated with preoperative PCS scores (r = 0.53, P  <  0.001) and OKSs (r = –0.25, P  =  0.002). Higher postoperative pain was correlated with high preoperative pain (r = 0.424, P  <  0.001), PCS scores (r = 0.33, P  <  0.001), PainDETECT scores (r = 0.298, P  =  0.001), and lower CPM (r = –0.18, P  =  0.04). The combination of preoperative pain, PCS score, and CPM explained 20.5% of variance in follow-up pain. PCS scores had a significant effect on pain trajectory when accounting for patient variance (t  =  14.41, P  <  0.0005).

Conclusion

The combination of high preoperative clinical pain intensity, high levels of pain catastrophizing thoughts, and impaired CPM may predict long-term postoperative pain 12 months after surgery.
What is White Ignorance?
Authors: Martín Annette
Published: October 2020

In this paper, I identify a theoretical and political role for ‘white ignorance’, present three alternative accounts of white ignorance, and assess how well each fulfils this role. On the Willful Ignorance View, white ignorance refers to white individuals’ willful ignorance about racial injustice. On the Cognitivist View, white ignorance refers to ignorance resulting from social practices that distribute faulty cognitive resources. On the Structuralist View, white ignorance refers to ignorance that (1) results as part of a social process that systematically gives rise to racial injustice, and (2) is an active player in the process. I argue that, because of its greater power and flexibility, the Structuralist View better explains the patterns of ignorance that we observe, better illuminates the connection to white racial domination, and is overall better suited to the project of ameliorating racial injustice. As such, the Structuralist View should be preferred.
Multisystemic Increment of Cortical Thickness in Congenital Blind Children
Authors: Inuggi Alberto , Pichiecchio Anna , Ciacchini Benedetta , Signorini Sabrina , Morelli Federica , Gori Monica
Published: October 2020

It has been shown that the total or partial lack of visual experience is associated with a plastic reorganization at the brain level, more prominent in congenital blind. Cortical thickness (CT) studies, to date involving only adult subjects, showed that only congenital blind have a thicker cortex than age-matched sighted population while late blind do not. This was explained as a deviation from the physiological mechanism of initial neural growth followed by a pruning mechanism that, in congenital blind children, might be reduced by their visual deprivation, thus determining a thicker cortex. Since those studies involved only adults, it is unknown when these changes may appear and whether they are related to impairment degree. To address this question, we compared the CT among 28 children, from 2 to 12 years, with congenital visual impairments of different degree and an age-matched sighted population. Vertex-wise analysis showed that blind children, but not low vision one, had a thicker cortical surface in few clusters located in occipital, superior parietal, anterior-cingular, orbito-frontal, and mesial precentral regions. Our data suggest that the effect of visual impairment on determining thicker cortex is an early phenomenon, is multisystemic, and occurs only when blindness is almost complete.
Intrinsic Connectivity Changes Mediate the Beneficial Effect of Cardiovascular Exercise on Sustained Visual Attention
Authors: Lehmann Nico , Villringer Arno , Taubert Marco
Published: October 2020

Cardiovascular exercise (CE) is an evidence-based healthy lifestyle strategy. Yet, little is known about its effects on brain and cognition in young adults. Furthermore, evidence supporting a causal path linking CE to human cognitive performance via neuroplasticity is currently lacking. To understand the brain networks that mediate the CE–cognition relationship, we conducted a longitudinal, controlled trial with healthy human participants to compare the effects of a 2–week CE intervention against a non-CE control group on cognitive performance. Concomitantly, we used structural and functional magnetic resonance imaging to investigate the neural mechanisms mediating between CE and cognition. On the behavioral level, we found that CE improved sustained attention, but not processing speed or short-term memory. Using graph theoretical measures and statistical mediation analysis, we found that a localized increase in eigenvector centrality in the left middle frontal gyrus, probably reflecting changes within an attention-related network, conveyed the effect of CE on cognition. Finally, we found CE-induced changes in white matter microstructure that correlated with intrinsic connectivity changes (intermodal correlation). These results suggest that CE is a promising intervention strategy to improve sustained attention via brain plasticity in young, healthy adults.
Physical, chemical, and toxicological characterization of sulfated cellulose nanocrystals for food-related applications using in vivo and in vitro strategies
Authors: Ede James D , Ong Kimberly J , Mulenos Marina R , Pradhan Sahar , Gibb Matthew , Sayes Christie M , Shatkin Jo Anne
Published: October 2020

Cellulose nanocrystals (CNCs) are a next-generation cellulose product with many unique properties including applications in the food industry as a food additive, food coating, and in food-contact packaging material. While CNC is anticipated to be safe due to its similarity to the many forms of cellulose currently used as food additives, special consideration is given to it as it is the first manufactured form of cellulose that is nanoscale in both length and width. A proactive approach to safety has been adopted by manufacturers to demonstrate CNC safety toward responsible commercialization. As part of the safety demonstration, in vivo and in vitro testing strategies were commissioned side-by-side with conventional cellulose, which has been safely used in food for decades. Testing included a 90-day rodent feeding study as well as additional physical, chemical, and biological studies in vitro that follow European Food Safety Authority (EFSA) guidance to demonstrate the safe use of novel food ingredients. The strategy includes assessment of neat materials side-by-side with simulated digestion, mimicking conditions that occur along the gastrointestinal tract as well as intracellularly. An intestinal co-culture model examined any potential toxicological effects from exposure to either pristine or digested forms of CNC including cytotoxicity, metabolic activity, membrane permeability, oxidative stress, and proinflammatory responses. None of the studies demonstrated any toxicity via oral or simulated oral exposure. These studies demonstrate that CNC produced by InnoTech Alberta is similarly safe by ingestion as conventional cellulose with a no-observed-adverse-effect level of 2085.3 (males) and 2682.8 (females) mg/kg/day.
Acetaminophen Modulates the Expression of Steroidogenesis-Associated Genes and Estradiol Levels in Human Placental JEG-3 Cells
Authors: Addo Kezia A , Palakodety Niharika , Fry Rebecca C
Published: October 2020

Acetaminophen is the only medication recommended for pain and fever management during pregnancy. However, studies have reported an association between in utero acetaminophen and neurocognitive disorders later in life. Additionally, acetaminophen has been shown to have endocrine disrupting properties altering hormones critical for normal fetal development. As the placenta is an endocrine organ that produces hormones for fetal development, any attempts to elucidate the mechanism underlying in utero acetaminophen and birth outcomes must also focus on the placenta. The present study set out to examine the effect of acetaminophen on mRNA expression, protein expression, and hormone synthesis in placental JEG-3 cells. The analysis focused on genes involved in steroidogenesis and acetaminophen metabolism as well those with known roles as nuclear receptors and transporters. The results highlight that at high concentrations, acetaminophen reduced the gene expression of aromatase (CYP19A1) and type 1 3β-hydroxysteroid dehydrogenase (HSD3B1), and increased the expression of 17β-hydroxysteroid dehydrogenase (HSD17B1). Additionally, acetaminophen at high concentrations also reduced the protein expression of aromatase (CYP19A1). These effects were accompanied by a significant dose-dependent decrease in estradiol secretion. Estradiol plays an important role in the development of reproductive organs and the brain of the developing fetus. This study highlights the potential for acetaminophen to interfere with hormone regulation during pregnancy and underscores the need for additional studies aimed at understanding the endocrine disruption activity of acetaminophen during fetal development.
Predictors of Functional Dependence After COVID-19
Authors: Leigh Alexandra E. , McCall Jonathan , Burke Rebecca V. , Rome Robin , Raines Amanda M.
Published: October 2020

Objective

The aim of this study was to examine the impact of demographics, preexisting medical conditions, and in-hospital complications of COVID-19 infection on functional status at discharge.

Design and Participants

A retrospective chart review was conducted on 119 patients hospitalized for COVID-19 infection between March 1, 2020, and April 20, 2020. Demographics, preexisting medical conditions, and newly diagnosed COVID-19 complications were collected from electronic medical records and entered in a deidentified database.

Main Outcome

The primary outcome was functional status at discharge, as measured by independence in activities of daily living.

Results

Older age, respiratory failure, cardiac conditions, and thromboembolic complications all made a statistically significant contribution to functional dependence at discharge, with thromboembolic complications evincing the strongest association (odds ratio, 25.58).

Conclusion and Relevance

New diagnosis of thrombosis during COVID-19 hospitalization, a measure of COVID-19 disease severity, was the factor most associated with dependence in activities of daily living at discharge. Interestingly, preexisting conditions including hypertension, severe obesity, lung disease, and diabetes did not correlate with dependent functional status at discharge.
An unrecognized key population? Traditional treatment practices associated with HIV risk among traditional healers in rural South Africa
Authors: Audet Carolyn M. , Ngobeni Sizzy , Mkansi Mevian , Wafawanaka Floidy , Aliyu Muktar H. , Vermund Sten H. , Wagner Ryan G.
Published: October 2020

Objective:

To understand the risk of HIV acquisition through occupational exposure among rural South African traditional healers, notably via the practice of traditional skin incisions with razors.

Design:

A random sample of traditional healers living in South Africa participated in a cross-sectional survey that included a rapid HIV test.

Setting:

Rural Bushbuckridge district of Mpumalanga, South Africa.

Participants:

Traditional healers.

Intervention:

Pretest counseling, posttest counseling, and referral to care if HIV seropositive.

Main outcome measure(s):

HIV infection.

Results:

Among healers who reported a previous positive test result or accepted an HIV test (96%), HIV prevalence was 30% (95% confidence interval: 23–37%). During their careers, 98% of healers reported conducting at least one ‘vaccination’ (as traditional incisions are called), 32% reported always using gloves when conducting these procedures, 29 (14%) reported patient blood touching their bare skin. Healers who reported exposure to patient blood had a higher HIV prevalence than their nonexposed colleagues (adjusted risk ratio: 2.35, 95% confidence interval: 1.55–3.56, P = 0.001).

Conclusion:

Nearly all traditional healers are routinely performing minimally invasive skin incisions that could expose them to patient blood. The lack of training and access to personal protective equipment increase their risk of acquisition of blood–borne pathogens, including HIV. Given the widespread practice of traditional skin incisions across southern Africa, and the higher levels of HIV among traditional healers exposed to patient blood, it is likely that traditional healers are a hitherto unrecognized key population at disproportionate risk of acquiring HIV.
Assessing self-reported discrimination among men who have sex with men (MSM)
Authors: Whiteman Ari , Baugher Amy , Sionean Catlainn
Published: October 2020

Objectives:

To determine the prevalence of four forms of sexual identity discrimination among MSM in 23 US metropolitan statistical areas, examine racial/ethnic and socioeconomic disparities in each form of discrimination.

Methods:

We examined interview data collected during 2017 for National HIV Behavioral Surveillance (n = 10 029 respondents) and used generalized linear models to assess the association between the prevalence of reported discrimination during the previous 12 months and selected sociodemographic groups.

Results:

Overall, 34% of participants reported experiencing verbal discrimination; 16%, discrimination in a workplace, school, or a healthcare setting; and 8%, physical assault. MSM who had reported experiencing discrimination were most likely to be young, had achieved lower education, and had lower incomes. High prevalence of reported discrimination was associated with young age, lower education, lower household income, sexual identity disclosure, and lower perceived community tolerance of gay or bisexual persons.

Conclusion:

MSM discrimination affects different groups and occurs in multiple settings. Addressing discrimination should be an integral aspect of multifaceted efforts to improve MSM health.
Risk of birth defects and perinatal outcomes in HIV-infected women exposed to integrase strand inhibitors during pregnancy
Authors: Sibiude Jeanne , Le Chenadec Jérôme , Mandelbrot Laurent , Dollfus Catherine , Matheron Sophie , Lelong Nathalie , Avettand-Fenoel Véronique , Brossard Maud , Frange Pierre , Reliquet Véronique , Warszawski Josiane , Tubiana Roland
Published: October 2020

Objectives:

Following an alert on neural tube defects and dolutegravir, we sought to evaluate if the exposure integrase strand transfer inhibitors (INSTIs) at conception was associated with birth defects or other adverse pregnancy outcomes.

Methods:

In the prospective national French Perinatal Cohort (EPF), we studied birth defects and other perinatal outcomes by matching each pregnant woman exposed to INSTIs with a pregnant woman exposed to darunavir/ritonavir receiving the same backbone of nucleoside reverse transcriptase inhibitors and matched for other characteristics such as age, geographic origin, centre and year of delivery.

Results:

Among 808 women exposed to INSTIs during pregnancy (raltegravir = 703, dolutegravir = 57 and elvitegravir = 48), we reported a slightly higher rate of birth defects in infants exposed at conception to raltegravir (6.7%) vs. infants exposed to raltegravir later in pregnancy: 2.9% if initiated during pregnancy as first-line, and 2.5% as second-line treatment,  P =0.04. When compared with matched controls, raltegravir exposure at conception was not significantly associated with birth defects: 6.4 vs. 2.3%, P = 0.08. There was no cluster of birth defect type and no neural tube defects were observed. Other perinatal outcomes, such as preterm birth and stillbirths, did not differ significantly between raltegravir-exposed women and matched counterparts. No difference in any outcome was observed for elvitegravir/cobicistat or dolutegravir.

Conclusion:

We found a nonsignificant trend for an association between exposure to raltegravir at conception and birth defects, which needs to be evaluated by larger prospective surveillance data, as these drugs are increasingly prescribed in women living with HIV.
A high-throughput microfluidic nano-immunoassay for detecting anti-SARS-CoV-2 antibodies in serum or ultra-low volume dried blood samples
Authors: Swank Zoe , Michielin Grégoire , Yip Hon Ming , Cohen Patrick , Andrey Diego O. , Vuilleumier Nicolas , Kaiser Laurent , Eckerle Isabella , Meyer Benjamin , Maerkl Sebastian J.
Published: October 2020

Novel technologies are needed to facilitate large-scale detection and quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies in human blood samples. Such technologies are essential to support seroprevalence studies, vaccine clinical trials, and to monitor quality and duration of immunity. We developed a microfluidic nano-immunnoassay for the detection of anti-SARS-CoV-2 IgG antibodies in 1024 samples per device. The method achieved a specificity of 100% and a sensitivity of 98% based on the analysis of 289 human serum samples. To eliminate the need for venipuncture, we developed low-cost, ultra-low volume whole blood sampling methods based on two commercial devices and repurposed a blood glucose test strip. The glucose test strip permits the collection, shipment, and analysis of 0.6µL whole blood easily obtainable from a simple fingerprick. The nano-immunoassay platform achieves high-throughput, high sensitivity and specificity, negligible reagent consumption, and a decentralized and simple approach to blood sample collection. We expect this technology to be immediately applicable to current and future SARS-CoV-2 related serological studies and to protein biomarker diagnostics in general.
Extracting Brain Disease-Related Connectome Subgraphs by Adaptive Dense Subgraph Discovery
Authors: Wu Qiong , Huang Xiaoqi , Culbreth Adam , Waltz James , Hong Elliot , Chen Shuo
Published: October 2020

Group-level brain connectome analysis has attracted increasing interest in neuropsychiatric research with the goal of identifying connectomic subnetworks (subgraphs) that are systematically associated with brain disorders. However, extracting disease-related subnetworks from the whole brain connectome has been challenging, because no prior knowledge is available regarding the sizes and locations of the subnetworks. In addition, neuroimaging data is often mixed with substantial noise that can further obscure informative subnetwork detection. We propose a likelihood-based adaptive dense subgraph discovery (ADSD) model to extract disease-related subgraphs from the group-level whole brain connectome data. Our method is robust to both false positive and false negative errors of edge-wise inference and thus can lead to a more accurate discovery of latent disease-related connectomic subnetworks. We develop computationally efficient algorithms to implement the novel ADSD objective function and derive theoretical results to guarantee the convergence properties. We apply the proposed approach to a brain fMRI study for schizophrenia research and identify well-organized and biologically meaningful subnetworks that exhibit schizophrenia-related salience network centered connectivity abnormality. Analysis of synthetic data also demonstrates the superior performance of the ADSD method for latent subnetwork detection in comparison with existing methods in various settings.
Elevated antiviral, myeloid and endothelial inflammatory markers in severe COVID-19
Authors: Thwaites Ryan S , Sevilla Uruchurtu Ashley Sanchez , Siggins Matthew , Liew Felicity , Russell Clark D , Moore Shona C , Carter Edwin , Abrams Simon , Short Charlotte-Eve , Thaventhiran Thilipan , Bergstrom Emma , Gardener Zoe , Ascough Stephanie , Chiu Christopher , Docherty Annemarie B , Hunt David , Crow Yanick J , Solomon Tom , Taylor Graham P , Turtle Lance , Harrison Ewen M , Semple Malcolm G , Baillie J Kenneth , Openshaw Peter JM
Published: October 2020

Introductory paragraph

The mechanisms that underpin COVID-19 disease severity, and determine the outcome of infection, are only beginning to be unraveled. The host inflammatory response contributes to lung injury, but circulating mediators levels fall below those in classical ‘cytokine storms’. We analyzed serial plasma samples from 619 patients hospitalized with COVID-19 recruited through the prospective multicenter ISARIC clinical characterization protocol U.K. study and 39 milder community cases not requiring hospitalization. Elevated levels of numerous mediators including angiopoietin-2, CXCL10, and GM-CSF were seen at recruitment in patients who later died. Markers of endothelial injury (angiopoietin-2 and von-Willebrand factor A2) were detected early in some patients, while inflammatory cytokines and markers of lung injury persisted for several weeks in fatal COVID-19 despite decreasing antiviral cytokine levels. Overall, markers of myeloid or endothelial cell activation were associated with severe, progressive, and fatal disease indicating a central role for innate immune activation and vascular inflammation in COVID-19.
Anxiety disorders and asthma among adolescents in urban Uganda: the role of early life exposures
Authors: Mpairwe Harriet , Mpango Richard Stephen , Sembajjwe Wilber , Webb Emily L , Elliott Alison M , Pearce Neil , Kinyanda Eugene
Published: October 2020

Background

The reasons for the association between anxiety disorders and asthma are not fully established, and data from Africa is sparse. We investigated whether the association between anxiety disorders and asthma among adolescents may be partly related to shared exposures in early life.

Methods

We conducted a case-control study among adolescents (12-17 years) with and without asthma in Wakiso District, an urban area in Uganda. Anxiety disorders were diagnosed by the Youth Inventory-4R (YI-4R), a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) referenced instrument. For this report, we focus on generalized anxiety disorder (GAD), panic disorder and social anxiety disorder. Asthma was doctor-diagnosed by study clinicians. We used questionnaires to collect data on early life exposures. The data were analysed using multiple logistic regression models.

Results

We enrolled 162 adolescents. Adolescents with asthma were more likely to have any of three anxiety disorders (44.6%) than adolescents without asthma (21.4%) [adjusted odds ratio (AOR) 2.68, 95% confidence interval (CI) 1.30-5.53, p-value=0.007]. The association was strong for GAD (AOR 4.49, 95% CI 1.48-13.56) and panic disorder (AOR 5.43, 95% CI 2.11-14.02), but not for social anxiety disorder (1.46, 95% CI 0.63-3.37). The early life risk factors associated with anxiety disorders among adolescents were similar to asthma risk factors previously published, including urban residence at birth [AOR 3.42 (1.29-9.09)] and during most of the first five years of life [AOR 2.87 (1.07-7.66)], father’s tertiary education [AOR 2.09 (1.00-4.37)], and adolescent’s history of other allergy-related diseases [AOR 4.64 (1.66-13.00)].

Conclusion

We confirm a positive association between anxiety disorders and asthma among adolescents in urban Uganda. The early life risk factors associated with anxiety disorders among adolescents were similar to those for asthma in the same age-group, suggesting shared underlying causes.
Heart failure grading using single-lead electrocardiography
Authors: Hasumi Eriko , Fujiu Katsuhito , Chen Ying , Shimizu Yu , Oshima Tsukasa , Matsunaga Hiroshi , Matsuda Jun , Matsubara Takumi J , Fukuma Nobuaki , Yuxiang Liu , Sugita Junichi , Nakayama Yukiteru , Saga Akiko , Oguri Gaku , Kojima Toshiya , Maru Yujin , Shoda Morio , Komuro Issei
Published: October 2020

Convolutional neural networks (CNNs) applied to electrocardiograms (ECGs) have been showing utility for detecting left ventricular (LV) dysfunction1. Although early detection of reduced LV ejection fraction (rEF) could improve handling of heart failure (HF) with rEF (HFrEF), it is not sufficient to detect HF with preserved EF (HFpEF). Here we developed a CNN algorithm to classify the severity of HF based on single-lead ECG data, irrespective of EF. We trained a CNN using ECG data and the HF classification from 7,865 patients with HF. The CNN achieved an area under the receiver-operating characteristic curve (AUC) of 0.996 for distinguishing patients with HF of various severity from healthy controls. It is anticipated that early detection of HF and therapeutic management of HF patients can be improved by employing this CNN with a single-lead ECG device.
Fast-Bonito: A Faster Basecaller for Nanopore Sequencing
Authors: Xu Zhimeng , Mai Yuting , Liu Denghui , He Wenjun , Lin Xinyuan , Xu Chi , Zhang Lei , Meng Xin , Mafofo Joseph , Zaher Walid Abbas , Li Yi , Qiao Nan
Published: October 2020

Oxford Nanopore Technologies (ONT) is a promising sequencing technology that could generate relatively longer sequencing reads compared to the next generation sequencing (NGS) technology. The base calling process is very important for TGS. It translates the original electrical signals from the sequencer to the nucleotide sequence. By doing that, the base calling could significantly influence the accuracy of downstream analysis. Bonito is a recently developed basecaller based on deep neuron network, the neuron network architecture of which is composed of a single convolutional layer followed by three stacked bidirectional GRU layers. Although Bonito achieved the state-of-the-art accuracy, its speed is so slow that it is not likely to be used in production. We therefore implement Fast-Bonito, which introduces systematic optimization to speed up Bonito. Fast-Bonito archives 53.8% faster than the original version on NVIDIA V100 and could be further speed up by HUAWEI Ascend 910 NPU, achieving 565% faster than the original version. The accuracy of Fast-Bonito is also slightly higher than the original Bonito.
Genome-wide methylation data improves dissection of the effect of smoking on body mass index
Authors: Amador Carmen , Zeng Yanni , Barber Michael , Walker Rosie , Campbell Archie , McIntosh Andrew M. , Evans Kathryn L. , Porteous David , Hayward Caroline , Wilson James F. , Navarro Pau , Haley Chris S.
Published: October 2020

Variation in obesity-related traits has a genetic basis with heritabilities between 40 and 70%. While the global obesity pandemic is usually associated with environmental changes related to lifestyle and socioeconomic changes, most genetic studies do not include all relevant environmental covariates, so genetic contribution to variation in obesity-related traits cannot be accurately assessed. Some studies have described interactions between a few individual genes linked to obesity and environmental variables but there is no agreement on their total contribution to differences between individuals. Here we compared self-reported smoking data and a methylation-based proxy to explore the effect of smoking and genome-by-smoking interactions on obesity related traits from a genome-wide perspective to estimate the amount of variance they explain. Our results indicate that exploiting omic measures can improve models for complex traits such as obesity and can be used as a substitute for, or jointly with, environmental records to better understand causes of disease.
Ocean Acidification Amplifies the Olfactory Response to 2-Phenylethylamine: Altered Cue Reception as a Mechanistic Pathway?
Authors: Schirrmacher Paula , Roggatz Christina C. , Benoit David M. , Hardege Jörg D.
Published: October 2020

With carbon dioxide (CO2) levels rising dramatically, climate change threatens marine environments. Due to increasing CO2concentrations in the ocean, pH levels are expected to drop by 0.4 units by the end of the century. There is an urgent need to understand the impact of ocean acidification on chemical-ecological processes. To date, the extent and mechanisms by which the decreasing ocean pH influences chemical communication are unclear. Combining behaviour assays with computational chemistry, we explore the function of the predator related cue 2-phenylethylamine (PEA) for hermit crabs (Pagurus bernhardus) in current and end-of-the-century oceanic pH. We demonstrate that this dietary predator cue for mammals and sea lampreys is an attractant for hermit crabs. Furthermore, we show that the potency of the cue increases at pH levels expected for the year 2100. In order to explain this increased potency, we assess changes to PEA’s conformational and charge-related properties as one potential mechanistic pathway. Using quantum chemical calculations validated by NMR spectroscopy, we characterise the different protonation states of PEA in water. We show how protonation of PEA could affect receptor-ligand binding, using a possible model receptor for PEA (human TAAR1). Investigating potential mechanisms of pH dependent effects on olfactory perception of PEA and the respective behavioural response, our study advances the understanding of how ocean acidification interferes with the sense of smell and thereby might impact essential ecological interactions in marine ecosystems.
Transcranial Bipolar Direct Current Stimulation of the Frontoparietal Cortex Reduces Ketamine-Induced Oscillopathies: A Pilot Study in the Sedated Rat
Authors: Lahogue Caroline , Pinault Didier
Published: October 2020

During the prodromal phase of schizophrenia with its complex and insidious clinical picture, electroencephalographic recordings detect widespread oscillation disturbances (or oscillopathies). Neural oscillations are electro-biomarkers of the connectivity state within systems. A single systemic administration of ketamine, a non-competitive NMDA glutamate receptor antagonist, transiently reproduces the oscillopathies with a clinical picture reminiscent of the psychosis prodrome. This acute pharmacological model may help the research and development of innovative treatments against the psychotic transition. Transcranial electrical stimulation is recognized as an appropriate non-invasive therapeutic modality since it can increase cognitive performance and modulate neural oscillations with little or no side effects. Therefore, our objective was to set up, in the sedated adult rat, a stimulation method able to normalize the ketamine-induced oscillopathies. Unilateral transcranial frontoparietal anodal stimulation by direct current (<+1 mA) was applied in ketamine-treated rats. A concomitant electroencephalographic recording of the parietal cortex measured the stimulation effects on its spontaneously-occurring oscillations. A 5-min bipolar anodal tDCS immediately and quickly reduced, significantly with an intensity-effect relationship, the ketamine-induced oscillopathies at least in the bilateral parietal cortex. A duration effect was also recorded. These preliminary neurophysiological findings are promising for developing a therapeutic proof-of-concept against neuropsychiatric disorders.
Isolating the role of corticosterone in the hypothalamic-pituitary-gonadal genomic stress response
Authors: Austin Suzanne H. , Harris Rayna , Booth April M. , Lang Andrew S. , Farrar Victoria S. , Krause Jesse S. , Hallman Tyler A. , MacManes Matthew , Calisi Rebecca M.
Published: October 2020

The negative impacts of stress on reproduction have long been studied. A large focus of investigation has centered around the effects of the adrenal steroid hormone corticosterone (CORT) on a system of tissues vital for reproduction, the hypothalamus of the brain, the pituitary gland, and the gonads (the HPG axis). Investigations of the role of CORT on the HPG axis have predominated the stress and reproductive biology literature, potentially overshadowing other influential mediators. To gain a more complete understanding of how elevated CORT, characteristic of the stress response, affects the activity of the HPG axis, we experimentally examined its role at the level of the genome in both male and female rock doves (Columba livia). We exogenously administrated CORT to mimic circulating levels during the stress response, specifically 30 min of restraint stress, an experimental paradigm known to increase circulating corticosterone in vertebrates. We examined all changes in genomic transcription within the HPG axis as compared to both restraint-stressed birds and vehicle-injected controls, as well as between the sexes. We report causal and sex-specific effects of CORT on the HPG stress response at the level of the transcriptome. Restraint stress caused 1567 genes to uniquely differentially express while elevated circulating CORT was responsible for the differential expression of 304 genes. Only 108 genes in females and 8 in males differentially expressed in subjects who underwent restraint stress and those who were given exogenous CORT. In response to CORT elevation characteristic of the stress response, both sexes shared the differential expression of 5 genes,KCNJ5, CISH, PTGER3, CEBPD, andZBTB16, all located in the pituitary. The known functions of these genes suggest potential influence of elevated CORT on immune function and prolactin synthesis. Gene expression unique to each sex indicated that elevated CORT affected more gene transcription in females than males (78 genes versus 3 genes, respectively). To our knowledge, this is the first study to isolate the role of CORT in HPG genomic transcription during a stress response. These results provide novel targets for new lines of further investigation and therapy development. We present an extensive and openly accessible view of the role corticosterone in the HPG genomic stress response, offering novel gene targets to inspire new lines of investigation of stress-induced reproductive dysfunction. Because the HPG system is well-conserved across vertebrates, these data have the potential to inspire new therapeutic strategies for reproductive dysregulation in multiple vertebrate systems, including our own.
Modulation of sleep-courtship balance by nutritional status inDrosophila
Authors: Duhart José M. , Baccini Victoria , Zhang Yanan , Machado Daniel R. , Koh Kyunghee
Published: October 2020

Sleep is essential but incompatible with other behaviors, and thus sleep drive competes with other motivations. We previously showedDrosophilamales balance sleep and courtship via octopaminergic neurons that act upstream of courtship-regulating P1 neurons (Machado et al., 2017). Here we show nutrition modulates the sleep-courtship balance and identify sleep-regulatory neurons downstream of P1 neurons. Yeast-deprived males exhibited attenuated female-induced nighttime sleep loss yet normal daytime courtship, which suggests male flies consider nutritional status in deciding whether the potential benefit of pursuing female partners outweighs the cost of losing sleep. Trans-synaptic tracing and calcium imaging identified dopaminergic neurons projecting to the protocerebral bridge (DA-PB) as postsynaptic partners of P1 neurons. Activation of DA-PB neurons led to reduced sleep in normally fed but not yeast-deprived males. Additional PB-projecting neurons regulated male sleep, suggesting several groups of PB-projecting neurons act downstream of P1 neurons to mediate nutritional modulation of the sleep-courtship balance.
idCOV: a pipeline for quick clade identification of SARS-CoV-2 isolates
Authors: Zhu Xun , Chang Ti-Cheng , Webby Richard , Wu Gang
Published: October 2020

idCOV is a phylogenetic pipeline for quickly identifying the clades of SARS-CoV-2 virus isolates from raw sequencing data based on a selected clade-defining marker list. Using a public dataset, we show that idCOV can make equivalent calls as annotated by Nextstrain.org on all three common clade systems using user uploaded FastQ files directly. Web and equivalent command-line interfaces are available. It can be deployed on any Linux environment, including personal computer, HPC and the cloud. The source code is available athttps://github.com/xz-stjude/idcov. A documentation for installation can be found athttps://github.com/xz-stjude/idcov/blob/master/README.md.
The assembled and annotated genome of the pigeon louseColumbicola columbae, a model ectoparasite
Authors: Baldwin-Brown James G. , Villa Scott M. , Vickrey Anna I. , Johnson Kevin P. , Bush Sarah E. , Clayton Dale H. , Shapiro Michael D.
Published: October 2020

The pigeon louseColumbicola columbaeis a longstanding and important model for studies of ectoparasitism and host-parasite coevolution. However, a deeper understanding of its evolution and capacity for rapid adaptation is limited by a lack of genomic resources. Here, we present a high-quality draft assembly of theC. columbaegenome, produced using a combination of Oxford Nanopore, Illumina, and Hi-C technologies. The final assembly is 208 Mb in length, with 12 chromosome-size scaffolds representing 98.1% of the assembly. For gene model prediction, we used a novel clustering method (wavy_choose) for Oxford Nanopore RNA-seq reads to feed into theMAKERannotation pipeline. High recovery of conserved single-copy orthologs (BUSCOs) suggests that our assembly and annotation are both highly complete and highly accurate. Consistent with the results of the only other assembled louse genome,Pediculus humanus, we find thatC. columbaehas a relatively low density of repetitive elements, the majority of which are DNA transposons. Also similar toP. humanus, we find a reduced number of genes encoding opsins, G protein-coupled receptors, odorant receptors, insulin signaling pathway components, and detoxification proteins in theC. columbaegenome, relative to other insects. We propose that such losses might characterize the genomes of obligate, permanent ectoparasites with predictable habitats, limited foraging complexity, and simple dietary regimes. The sequencing and analysis for this genome were relatively low-cost, and took advantage of a new clustering technique for Oxford Nanopore RNAseq reads that will be useful to future genome projects.
A velocity plan with internal feedback control best explains modulation of saccade kinematics during eye-hand coordination
Authors: V Varsha , Gopal Atul , Jana Sumitash , Padhi Radhakant , Murthy Aditya
Published: October 2020

Fast movements like saccadic eye movements that occur in the absence of sensory feedback are often thought to be under internal feedback control. In this framework, a desired input in the form of desired displacement signal is widely believed to be encoded in a spatial map of the superior colliculus (SC). This is then converted into a dynamic velocity signal that drives the oculomotor neurons. However, recent evidence has shown the presence of a dynamic signal within SC neurons, which correlates with saccade velocity. Hence, we used models based on optimal control theory to test whether saccadic execution could be achieved by a velocity based internal feedback controller. We compared the ability of a trajectory control model based on velocity to that of an endpoint control model based on final displacement to capture saccade behavior of modulation of peak saccade velocity by the hand movement, independent of the saccade amplitude. The trajectory control model tracking the desired velocity in optimal feedback control framework predicted this saccade velocity modulation better than an endpoint control model. These results suggest that the saccadic system has the flexibility to incorporate a velocity plan based internal feedback control that is imposed by task context.

NEW & NOTEWORTHY

We show that the saccade generation system may use an explicit velocity tracking controller when demand arises. Modulation of peak saccade velocity due to modulation of the velocity of the accompanying hand movement was better captured using a velocity tracking stochastic optimal control model compared to an endpoint model of saccade control. This is the first evidence of trajectory planning and control for the saccadic system based on optimal control theory.