bluuebunny/crossref_metadata_2025 huggingface dataset:
Calciphylaxis-Associated Cutaneous Vascular Calcification in Noncalciphylaxis Patients
Authors: Chaudet Kristine M. , Dutta Puja , Nigwekar Sagar U. , Nazarian Rosalynn M.
Published: July 2020

Calciphylaxis is a highly morbid disease that is strongly associated with chronic kidney disease (CKD); however, the histologic criteria for diagnosis have not been well established nor have their specificity for calciphylaxis been determined. This retrospective study aimed to examine the prevalence of histologic features commonly associated with calciphylaxis in noncalciphylaxis patients. We also sought to evaluate whether these features may be more prevalent in patients with CKD. To assess this, healthy marginal skin tissue from above-the-knee amputation specimens was compared between patients with CKD (n = 23) and without CKD (n = 47). Intravascular calcification of capillaries or small-to-medium arterioles was detected on von Kossa stain in 40.0% of the entire cohort. Capillary calcification and intravascular thrombosis were more prevalent in patients with CKD. Finely stippled capillary calcification was present in 26.1% of patients with CKD versus 8.5% of patients without CKD (P = 0.0484), and intravascular thrombosis was present in 8.7% of patients with CKD and 0.0% of patients without CKD (P = 0.0403). None of the patients in this study had clinical evidence of calciphylaxis at presentation and in at least a 1-year follow-up period. This study confirms that the histologic features previously associated with calciphylaxis are nonspecific and are more prevalent in patients with CKD.
The Road to Transfusion-free Craniosynostosis Repair in Children Less Than 24 Months Old: A Quality Improvement Initiative
Authors: Beethe Amy B. , Spitznagel Rachel A. , Kugler Jane A. , Goeller Jessica K. , Franzen Marcellene H. , Hamlin Ryan J. , Lockhart Thomas J. , Lyden Elizabeth R. , Glogowski Kimberly R. , LeRiger Michelle M.
Published: July 2020

Introduction:

Pediatric craniofacial reconstruction has historically resulted in extensive blood loss necessitating transfusion. This single-center quality improvement initiative evaluates the impact of perioperative practice changes on the allogeneic transfusion rate for children 24 months and younger of age undergoing craniofacial reconstruction.

Methods:

At project initiation, an appointed core group of anesthesiologists provided all intraoperative anesthetic care for patients undergoing craniofacial reconstruction. Standardized anesthetic guidelines established consistency between providers. Using the Plan-do-check-act methodology, practice changes had been implemented and studied over a 5-year period. Improvement initiatives included developing a temperature-management protocol, using a postoperative transfusion protocol, administering intraoperative tranexamic acid, and a preincisional injection of 0.25% lidocaine with epinephrine. For each year of the project, we acquired data for intraoperative and postoperative allogeneic transfusion rates.

Results:

A cohort of 119 pediatric patients, ages 4–24 months, underwent anterior or posterior vault reconstruction for craniosynostosis at a tertiary children’s hospital between March 2013 and November 2018. Intraoperative and postoperative transfusion of allogeneic blood products in this cohort decreased from 100% preintervention to 22.7% postintervention.

Conclusions:

Interdepartmental collaboration and practice modifications using sequential Plan-do-check-act cycles resulted in a bundle of care that leads to a sustainable decrease in the rate of intraoperative and postoperative allogeneic blood transfusions in patients less than 24 months of age undergoing craniosynostosis repair. This bundle decreases the risk of transfusion-related morbidity for these patients. Other institutions looking to achieve similar outcomes can implement this project.
Antiviral and virucidal effects of curcumin on transmissible gastroenteritis virus in vitro
Authors: Li Yaoming , Wang Jing , Liu Yinchuan , Luo Xiang , Lei Weiqiang , Xie Lilan
Published: July 2020

Emerging coronaviruses represent serious threats to human and animal health worldwide, and no approved therapeutics are currently available. Here, we used Transmissible gastroenteritis virus (TGEV) as the alpha-coronavirus model, and investigated the antiviral properties of curcumin against TGEV. Our results demonstrated that curcumin strongly inhibited TGEV proliferation and viral protein expression in a dose-dependent manner. We also observed that curcumin exhibited direct virucidal abilities in a dose-, temperature- and time-dependent manner. Furthermore, time-of-addition assays showed that curcumin mainly acted in the early phase of TGEV replication. Notably, in an adsorption assay, curcumin at 40 µM resulted in a reduction in viral titres of 3.55 log TCID50 ml–1, indicating that curcumin possesses excellent inhibitory effects on the adsorption of TGEV. Collectively, we demonstrate for the first time that curcumin has virucidal activity and virtual inhibition against TGEV, suggesting that curcumin might be a candidate drug for effective control of TGEV infection.
Preclinical and first-in-human-brain-cancer applications of [18F]poly-(ADP-ribose) polymerase inhibitor PET/MR
Authors: Young Robert J , De Souza França Paula Demétrio , Pirovano Giacomo , Piotrowski Anna F , Nicklin Philip J , Riedl Christopher C , Schwartz Jazmin , Bale Tejus A , Donabedian Patrick L , Kossatz Susanne , Burnazi Eva M , Roberts Sheryl , Lyashchenko Serge K , Miller Alexandra M , Moss Nelson S. , Fiasconaro Megan , Zhang Zhigang , Mauguen Audrey , Reiner Thomas , Dunphy Mark P
Published: July 2020

We report pre-clinical and first-in-human-brain-cancer data using a targeted poly(ADP-ribose)polymerase1 (PARP1) binding PET tracer, [18F]PARPi, as a diagnostic tool to differentiate between brain cancers and treatment related changes. In a pre-clinical mouse model, we illustrated that [18F]PARPi crosses the blood-brain barrier and specifically binds to PARP1 overexpressed in cancer cell nuclei. In humans, we demonstrated high [18F]PARPi uptake on PET/MR in active brain cancers and low uptake in treatment related changes, independent of blood brain-barrier disruption. Immunohistochemistry results confirmed higher PARP1 expression in cancers than non-cancers. Specificity was also corroborated by blocking fluorescent tracer uptake with excess of unlabeled PARP inhibitor in fresh cancer tissue derived from a patient. Although larger studies are necessary to confirm and further explore this tracer, we describe an encouraging role for the use of [18F]PARPi as a diagnostic tool in evaluating patients with brain cancers and possible treatment related changes.

One Sentence summary

PET imaging with [18F]PARPi can differentiate active brain cancer from treatment related changes with encouraging results for use during treatment follow-up.
The brief comparison of the operational efficiency of pool-testing strategies for COVID-19 mass testing in PCR laboratories
Authors: Vechera Kirill
Published: July 2020

This paper addresses the operational efficiency of different pool-testing strategies in typical scenarios of a PCR laboratory working in mass testing for COVID-19 with different values of prevalence, limitations and conditions of testing, and priorities of optimization.

The research employs a model of the laboratory’s testing process, created after interviewing of PCR laboratories and studying their operations. The limitations and operational characteristics of this model were applied in a simulation of the testing process with different pool-testing strategies managed by a computer program developed in the LOMT project.

The efficiency indicators assessed are the number of assays needed to obtain results of a batch of specimens, the number of specimens identified after the first analysis, and total time to obtain all results.

Depending on prevalence, constraints of testing, and priorities of optimization, different pool-testing strategies provide the best operational efficiency. The binary splitting algorithm provides the maximum reduction of the number of assays: from 1.99x reduction for a high prevalence (10%) to 25x reduction for a low prevalence (0.1%), while other algorithms provide the least amount of time to obtain results or the maximum number of the specimens classified after the first analysis.
Changes in SARS-CoV-2 Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies
Authors: Fenwick Craig , Croxatto Antony , Coste Alix T. , Pojer Florence , André Cyril , Pellaton Céline , Farina Alex , Campos Jérémy , Hacker David , Lau Kelvin , Bosch Berend-Jan , Nussle Semira Gonseth , Bochud Murielle , D’Acremont Valerie , Trono Didier , Greub Gilbert , Pantaleo Giuseppe
Published: July 2020

We have determined SARS-CoV-2-specific antibody responses in a cohort of 96 individuals with acute infection and in 578 individuals enrolled in a seroprevalence population study in Switzerland including three groups, i.e. subjects with previous RT-PCR confirmed SARS-CoV-2 infections (n=90), ‘positive patient contacts’ (n=177) and ‘random selected subjects’ (n=311). SARS-CoV-2 antibody responses specific to the Spike (S), in the monomeric and native trimeric forms, and/or the nucleocapsid (N) proteins were equally sensitive in the acute infection phase. Interestingly, as compared to anti-S antibody responses, those against the N protein appear to wane in the post-infection and substantially underestimated the proportion of SARS-CoV-2 infections in the groups of ‘patient positive contacts’, i.e. 10.9 to 32.2% reduction and in the ‘random selected’ general population, i.e. up to 45% reduction. The overall reduction in seroprevalence targeting only anti-N IgG antibodies for the total cohort ranged from 9.4 to 31%. Of note, the use of the S protein in its native trimer form was more sensitive as compared to monomeric S proteins.

These results indicate that the assessment of anti-S IgG antibody responses against the native trimeric S protein should be implemented to estimate SARS-CoV-2 infections in population-based seroprevalence studies.
Impact of Meteorological factors and population size on the transmission of Micro-size respiratory droplets based Coronavirus: A brief study of highly infected cities in Pakistan
Authors: Shahzadi Iram , Shahzadi Anum , Haider Junaid , Naz Sadia , Aamir Rai. M. , Haider Ali , Sharif Hafiz Rizwan , Khan Imran Mahmood , Ikram Muhammad
Published: July 2020

Ongoing Coronavirus epidemic (COVID-19) identified first in Wuhan, China posed huge impact on public health and economy around the globe. Both cough and sneeze based droplets or aerosols encapsulated COVID-19 particles are responsible for air borne transmission of this virus and caused unexpected escalation and high mortality worldwide. Current study intends to investigate correlation of COVID-19 epidemic with meteorological parameters particularly, temperature, rainfall, humidity, and wind speed along with population size. Data set of COVID-19 for highly infected cities of Pakistan was collected from the official website of National Institute of health (NIH). Spearman’s rank (rs) correlation coefficient test employed for data analysis revealed significant correlation between temperature minimum (TM), temperature average (TA), wind speed (WS) and population size (PS) with COVID-19 pandemic. Furthermore, receiver operating characteristics (ROC) curve was used to analyze the sensitivity of TA, WS, and PS on transmission rate of COVID-19 in selected cities of Pakistan. The results obtained for sensitivity and specificity analysis for all selected parameters signifies sensitivity and direct correlation of COVID-19 transmission with temperature variation, WS and PS. Positive correlation and strong association of PS parameter with COVID-19 pandemic suggested need of more strict actions and control measures for highly populated cities. These findings will be helpful for health regulatory authorities and policymakers to take specific measures to combat COVID-19 epidemic in Pakistan.
Evaluation of SARS-CoV-2 IgG antibody response in PCR positive patients: comparison of nine tests in relation with clinical data
Authors: Naaber Paul , Hunt Kaidi , Pesukova Jaana , Haljasmägi Liis , Rumm Pauliina , Peterson Pärt , Hololejenko Jelena , Eero Irina , Jõgi Piia , Toompere Karolin , Sepp Epp
Published: July 2020

Background

High number of SARS-CoV-2 antibody tests are available in different formats, detect different types of antibodies, and use different target proteins. Sensitivity of these tests varies and could be also related to clinical symptoms and testing time.

Methods

Serum samples from 97 COVID-19 patients and 100 controls were tested with 9 antibody tests (SNIBE, Epitope, Euroimmun, Roche, Abbott, DiaSorin, Biosensor, LIPS N, and LIPS S-RBD). The results were analyzed in context of clinical data.

Findings

Positivity rate was of tests was following: N-LIPS test (91.8% cases), Epitope (85.6%), Abbott and in-house LIPS S-RBD (both 84.5%), Roche (83.5%), Euroimmun (82.5%), DiaSorin (81.4%), SNIBE (70.1%), and Biosensor (64.9%). Agreement between tests varied (71-95%). Correlation between patient symptoms score and antibody value was test-dependent: varied from strongest in LIPS N (ρ=0.41; p<0.001) to nonsignificant (LIPS S-RBD). Testing time from symptoms influenced sensitivity in some tests more than another’s.

Interpretation

Sensitivity of tests varied highly and combination of different tests may improve it. Relation of results to symptoms and testing time was test-dependent. Thus, some antibody tests seems to be more sensitive to detect antibodies early and in asymptomatic patients than others.

Funding

Study was funded by SYNLAB Estonia and Estonian Research Council grant PRG377.

Research in context

Evidence before this study

High variation in COVID-19 antibody tests sensitivity has been described. Relation between antibody response and clinical cause has been found in some studies but not in others. It’s known that antibody response is time dependent, however seroconversion medians varied in different studies.

Added value of this study

We confirmed that SARS-CoV-2 antibody response depends on clinical symptoms and time of testing, but we also found that this relation is dependent on test setup and viral antigens used in the tests. This may explain contradictory results of previous studies.

Implications of all the available evidence

Our study has practical implications showing that not all antibody tests work uniformly well in symptomatic and asymptomatic cases and in different time periods from disease onset. This should be taken into consideration in clinical practice for diagnosing COVID-19 and in epidemiological studies evaluating the seroprevalence especially in asymptomatic population.
Public’s perceived importance of non-pharmacological interventions for COVID-19 control in Greece: preliminary evidence from a cross-sectional study
Authors: Boutsikari Eleni C. , Christakou Anna , Elpidoforou Michail , Kopsidas Ioannis , Nikolovienis Nicholas , Kardara Despina , Boutsikari Chrissoula C. , Triantafyllou Christos
Published: July 2020

Background

In the early stages of coronavirus disease 2019 (COVID-19) pandemic, while effective pharmaceutical approaches are pending, COVID-19 management relies primarily on non-pharmaceutical interventions (NPIs), such as social distancing, which requirepublic’s engagement and behavioral adjustment. This study aims to evaluate public’s perceived importance of the NPIs imposed for COVID-19 control in personal and public health protection in Greece.

Methods

This cross-sectional online study, enrolled 657 participants of the general Greek population in order to assess their beliefs and evaluate possible factors that influence their perceptions as regards NPI importance in personal and public health protection.

Results

Overall, Greeks considered NPIs important for health protection. The participants who were less likely to consider NPIs important were men (OR versus females=1.64, 95% CI:1.15 to 2.36, p=0.007), people younger than 40 years old (OR between ages over 40 versus ages below 40=0.48, 95% CI:0.34 to 0.68, p<0.001), and people who did not chose the Hellenic National Public Health Organization (EODY) to get informed about COVID-19 (OR of EODY versus other sources of information = 0.65, 95% CI:0.46-0.92, p= 0.014).

Conclusions

This study profiled Greek people who do and do not consider NPIs important, mainly as of their demographic features. Focused communicational strategies in certain population subgroups are recommended.
Geographic Barriers to Achieving Universal Health Coverage in a rural district of Madagascar
Authors: Garchitorena Andres , Ihantamalala Felana A , Révillion Christophe , Cordier Laura F , Randriamihaja Mauricianot , Razafinjato Benedicte , Rafenoarivamalala Feno H , Finnegan Karen E. , Andrianirinarison Jean-Claude , Rakotonirina Julio , Herbreteau Vincent , Bonds Matthew H
Published: July 2020

Poor geographic access can persist even when affordable and well-functioning health systems are in place, limiting efforts for universal health coverage (UHC). It is unclear how health facilities and community health workers contribute to achieving UHC. Using geographic information from thousands of patients in a rural district of Madagascar we evaluate how a health system strengthening (HSS) intervention aimed towards UHC affects the geography of primary care access. We find that facility-based interventions (user-fee exemptions, improved readiness) achieved high utilization rates only among populations who lived in close proximity to supported facilities. Scaling only facility-based HSS programs across the district would result in large gaps in health care access for the majority of the population. Community health provided major improvements in service utilization for children regardless of their distance from facilities. Our results have implications for UHC policies and suggest that greater emphasis on professionalized community health programs is essential.
Age structuring and spatial heterogeneity in prion protein gene (PRNP) polymorphism in white-tailed deer
Authors: Chafin Tyler K. , Douglas Marlis R. , Martin Bradley T. , Zbinden Zachery D. , Middaugh Christopher R. , Ballard Jennifer R. , Gray M. Cory , White Don , Douglas Michael E.
Published: July 2020

Chronic-wasting disease (CWD) is a prion-derived fatal neurodegenerative disease that has affected wild cervid populations on a global scale. Susceptibility has been linked unambiguously to several amino acid variants within the prion protein gene (PRNP). Quantifying their distribution across landscapes can provide critical information for agencies attempting to adaptively manage CWD. Here we attempt to further define management implications ofPRNPpolymorphism by quantifying the contemporary geographic distribution (i.e., phylogeography) ofPRNPvariants in hunter-harvested white-tailed deer (WTD;Odocoileus virginianus, N=1433) distributed across Arkansas (USA), including a focal spot for CWD since detection of the disease in February 2016. Of these,PRNPvariants associated with the well-characterized 96S non-synonymous substitution showed a significant increase in relative frequency among older CWD-positive cohorts. We interpreted this pattern as reflective of a longer life expectancy for 96S genotypes in a CWD-endemic region, suggesting either decreased probabilities of infection or reduced disease progression. Other variants showing statistical signatures of potential increased susceptibility, however, seemingly do so as an artefact of population structure. We also showed marked heterogeneity across the landscape in the prevalence of ‘reduced susceptibility’ genotypes. This may indicate, in turn, that differences in disease susceptibility among WTD in Arkansas are an innate, population-level characteristic that is detectable through phylogeographic analysis.
An offset ON-OFF receptive field is created by gap junctions between distinct types of retinal ganglion cells
Authors: Cooler Sam , Schwartz Gregory W.
Published: July 2020

Receptive fields (RFs) are a foundational concept in sensory neuroscience. The RF of a sensory neuron is shaped by the properties of its synaptic inputs from connected neurons. In the early visual system, retinotopic maps define a strict relationship between the location of a cell’s dendrites and its RF location in visual space1–3. Retinal ganglion cells (RGCs), the output cells of the retina, form dendritic mosaics that tile retinal space and have corresponding RF mosaics that tile visual space1,2. The precise location of dendrites in some RGCs has been shown to predict their RF shape4. Previously described ON-OFF RGCs have aligned dendrites in ON and OFF synaptic layers, so the cells respond to increments and decrements of light at the same locations in visual space5–8. Here we report a systematic offset between the ON and OFF RFs of an RGC type. Surprisingly, this property does not come from offset ON and OFF dendrites but instead arises from electrical synapses with RGCs of a different type. This circuit represents a new channel for direct communication between ON and OFF RGCs. Using a multi-cell model, we find that offset ON-OFF RFs could improve the precision with which edge location is represented in an RGC population.
Ultradian Rhythms in Heart Rate Variability and Distal Body Temperature Anticipate the Luteinizing Hormone Surge Onset
Authors: Grant Azure D. , Newman Mark , Kriegsfeld Lance J.
Published: July 2020

The human menstrual cycle is characterized by predictable patterns of physiological change across timescales, yet non-invasive anticipation of key events is not yet possible at individual resolution. Although patterns of reproductive hormones across the menstrual cycle have been well characterized, monitoring these measures repeatedly to anticipate the preovulatory luteinizing hormone (LH) surge is not practical for fertility awareness. In the present study, we explored whether non-invasive and high frequency measures of distal body temperature (DBT), sleeping heart rate (HR), sleeping heart rate variability (HRV), and sleep timing could be used to anticipate the preovulatory LH surge in women. To test this possibility, we used signal processing to examine these measures across the menstrual cycle. Cycles were examined from both pre- (n=45 cycles) and perimenopausal (n=10 cycles) women using days of supra-surge threshold LH and dates of menstruation for all cycles. For a subset of cycles, urinary estradiol and progesterone metabolites were measured daily around the time of the LH surge. Wavelet analysis revealed a consistent inflection point of ultradian rhythm (2-5 h) power of DBT and HRV that enabled anticipation of the LH surge at least 2 days prior to its onset in 100% of individuals. In contrast, the power of ultradian rhythms in heart rate, circadian rhythms in body temperature, and metrics of sleep duration and sleep timing were not predictive of the LH surge. Together, the present findings reveal fluctuations in distal body temperature and heart rate variability that consistently anticipate the LH surge and may aid in fertility awareness.

Key Points

Ultradian (2-5 h) rhythm power of distal body temperature and heart rate variability (RMSSD) exhibits a stereotyped inflection point and peak in the days leading up to the LH surge in premenopausal women.

Circadian rhythms of distal body temperature and single time-point/day metrics do not permit anticipation of the LH surge.

Measurement of continuous metabolic and autonomic outputs, enabling assessment of ultradian rhythms, may be of value to the fertility awareness method.
A spinoparabrachial circuit defined by Tacr1 expression drives pain
Authors: Barik Arnab , Sathyamurthy Anupama , Thompson James , Seltzer Mathew , Levine Ariel , Chesler Alexander
Published: July 2020

Painful stimuli evoke a mixture of sensations, negative emotions and behaviors. These myriad effects are thought to be produced by parallel ascending circuits working in combination. Here we describe a pathway from spinal cord to brain for ongoing pain. Activation of a defined subset of spinal projection neurons expressing Tacr1 evokes a full repertoire of somatotopically-directed coping behaviors in the absence of noxious input. These cells project to a tiny cluster of Tacr1-positive neurons in the superior lateral parabrachial nucleus (PBN-SL) that themselves are responsive to sustained but not acute noxious stimuli. Activation of these PBN-SLTacr1neurons alone does not trigger pain responses but instead serves to dramatically heighten nocifensive behaviors and suppress itch. Remarkably, mice with silenced PBN-SLTacr1neurons ignore long-lasting noxious stimuli. These data reveal a spinoparabrachial pathway that plays a key role in the sensation of ongoing pain.
Pseudogene-mediated DNA demethylation leads to oncogene activation
Authors: Kwon Junsu , Liu Yanjing V. , Gao Chong , Bassal Mahmoud A. , Jones Adrianna I. , Yang Junyu , Chen Zhiyuan , Ying Li , Yang Henry , Chen Leilei , Di Ruscio Annalisa , Tay Yvonne , Chai Li , Tenen Daniel G.
Published: July 2020

Despite being one of the leading causes of cancer-related deaths, there is an unmet clinical need for hepatocellular carcinoma (HCC) patients. The lack of effective treatment is, at least in part, due to our lack of understanding of the molecular pathogenesis of this disease. Oncofetal protein SALL4 is re-activated in patients with aggressive HCC along with other solid tumors and hematologic malignancies. This study identifies a previously unrecognized mechanism of SALL4 reactivation which is mediated by pseudogene-induced demethylation. Using a locus-specific demethylating technology, we identified the critical CpG region for SALL4 expression. We showed that SALL4 pseudogene 5 hypomethylates this region through interaction with DNMT1, resulting in SALL4 upregulation. Intriguingly, pseudogene 5 is significantly upregulated in a hepatitis B virus (HBV) model prior to SALL4 induction, and both are increased in HBV-HCC patients. Our results suggest that pseudogene-mediated demethylation represents a unique mechanism of oncogene activation in cancer.

Significance

Our study provides a mechanistic link between HBV infection, activation of the oncogene SALL4, and HCC. We reveal a previously undescribed capability of a pseudogene to epigenetically activate an oncogene by demethylation in a locus-specific manner.
Quantifying the monomer-dimer equilibrium of tubulin with mass photometry
Authors: Fineberg Adam , Surrey Thomas , Kukura Philipp
Published: July 2020

Theαβ-tubulin heterodimer is the fundamental building block of microtubules, making it central to several cellular processes. Despite the apparent simplicity of heterodimerisation, the associated energetics and kinetics remain disputed, largely due to experimental challenges associated with quantifying affinities in the <μM range. We use mass photometry to observe tubulin monomers and heterodimers in solution simultaneously, thereby quantifying theαβ-tubulin dissociation constant (8.48±1.22 nM) and its tightening in the presence of GTP (3.69±0.65 nM), at a dissociation rate >10−2s−1. Our results demonstrate the capabilities of mass photometry for quantifying protein-protein interactions and clarify the energetics and kinetics of tubulin heterodimerisation.

Abstract Figure
Undocumented migrants in the Netherlands: adverse life events, living conditions and mental health
Authors: Vollebregt Sandrine JC , Scholte Willem F , Hoogerbrugge Annette , Bolhuis Koen , Vermeulen Jentien
Published: July 2020

Background

Undocumented migrants have worse health and living conditions and poor access to health care.

Aims and objectives

To examine the prevalence and determinants of mental health problems in undocumented migrants.

Design

Observational study, integrating cross-sectional questionnaire data with retrospective electronic patient record data.

Methods

Undocumented migrants attending medical and psychological consultation hours of a Netherlands-based non-governmental organization, completed the Self-Reporting Questionnaire (SRQ). We examined scores of the instrument’s 24 items version (SRQ-24) and its 20 items version (SRQ-20). Correlations with determinants were estimated using parametric tests.

Results

On the SRQ-20, 85% of the sample (N=101) scored ≥8, the clinical cut-off value; mean=12.4 ± 4.6, range 0-20. Adverse life events like physical and sexual assault were reported in 37% of the medical records (N=99) and had a medium to large effect (Cohen’s d=0.76) on SRQ-24 scores.

Discussion

Mental health problems are common in undocumented migrants. Adverse life-events are critical determinants.
Clinical and molecular diagnostic study of 320 Chinese children with epilepsy by Genome Sequencing
Authors: Zou Dongfang , Wang Lin , Liao Jianxiang , Xiao Hongdou , Duan Jing , Zhang Tongda , Yin Zhenzhen , Zhou Jing , Yan Haisheng , Huang Yushan , Li Jianbiao , Zhan Nianji , Yang Ying , Ye Jingyu , Chen Fang , Zhu Shida , Wen Feiqiu , Guo Jian
Published: July 2020

Purpose

To evaluate the diagnostic value of Genome Sequencing(GS)in children with epilepsy.

Methods

We performed GS on 320 Chinese children with epilepsy and interpreted Single Nucleotide Variants (SNVs) and Copy Number Variant (CNVs) of all samples. The complete pedigree and clinical data of the probands were established and followed up. The clinical phenotypes, treatments, prognoses and genotypes of the patients were analyzed.

Results

Pathogenic/likely pathogenic variants were found in 122 of 320 children (38.13%), of whom, 92 (28.8%) had SNVs, 27 (8.4%) had CNVs, and three had both SNVs and CNVs. Among these variants, there were 3 CNVs of <100K in length. The most frequently mutated gene was SCN1A(10.9%,10/92),which is related to Dravet Syndrome, followed by PRRT2(8.7%,8/92), which is relevant to benign familial infantile epilepsy, TSC2(7.6%,7/92), which is associated with Tuberous Sclerosis. The most common recurrent CNVs were 17p13.3 deletion (18.5%, 5/27), 16p11.2 deletion syndrome (14.8%, 4/27), 15q11.2 deletion (11.1%, 3/27), which are related to epilepsy, developmental retardation and congenital abnormalities.

The diagnostic yield was higher as the age of seizure onset was smaller. The highest detection rate was 75% in whom developed seizures within one month after birth. 13.4% (43/320) cases were identified to be treatable based on GS. 1% (3/320) of epilepsy patients received direct therapeutic measures and demonstrated favorable prognosis.

Conclusion

GS can complete the genetic diagnosis, individualized treatment, and family reproductive guidance for patients. GS can replace Exome Sequencing and Chromosomal Microarray Analysis and is expected to be the first choice of genetic testing method for patients with epilepsy.
Analysis of 50,000 exome-sequenced UK Biobank subjects fails to identify genes influencing probability of psychiatric referral
Authors: Curtis David
Published: July 2020

Background

Depression is moderately heritable but there is no common genetic variant which has a major effect on susceptibility. It is possible that some very rare variants could have substantial effect sizes and these could be identified from exome sequence data.

Methods

Data from 50,000 exome-sequenced UK Biobank participants was analysed. Subjects were treated as cases if they had reported having seen a psychiatrist for “nerves, anxiety, tension or depression”. Gene-wise weighted burden analysis was performed to see if there were any genes or sets of genes for which there was an excess of rare, functional variants in cases.

Results

There were 5,872 cases and 43,862 controls. There were 22,028 informative genes but none produced a statistically significant result after correction for multiple testing. Of the 25 genes individually significant at p<0.001 none appeared to be a biologically plausible candidate. No set of genes achieved statistical significance after correction for multiple testing and those with the lowest p values again did not appear to be biologically plausible candidates.

Limitations

The phenotype is based on self-report and the cases are likely to somewhat heterogeneous. The number of cases is on the low side for a study of exome sequence data.

Conclusions

The results conform exactly with the expectation under the null hypothesis. It seems unlikely that depression genetics research will produce findings that might have a substantial clinical impact until far larger samples become available.
Towards middle-up analysis of polyclonal antibodies: subclass-specificN-glycosylation profiling of murine immunoglobulin G (IgG) by means of HPLC-MS
Authors: Blöchl Constantin , Regl Christof , Huber Christian G. , Winter Petra , Weiss Richard , Wohlschlager Therese
Published: July 2020

Advanced analytical strategies including top-down and middle-up HPLC-MS approaches have become powerful alternatives to classical bottom-up analysis for the characterization of therapeutic monoclonal antibodies. Here, we assess feasibility of middle-up analysis of polyclonal IgGs posing additional challenges due to extensive sequence variability. The presented workflow is based on Fc/2 portions as conserved subunits of IgGs and enables global profiling of subclasses and their glycosylation patterns, both of which influence IgG effector functions. To obtain subunits of murine IgGs, we established digestion with the bacterial protease SpeB. The resulting Fc/2 portions characteristic of different subclasses were subsequently analysed by ion-pair reversed-phase HPLC hyphenated to high-resolution mass spectrometry allowing relative quantification of IgG subclasses and theirN-glycosylation variants. In order to assess method capabilities in an immunological context, we applied the analytical workflow to polyclonal antibodies obtained from BALB/c mice immunized with the grass pollen allergen Phl p 6. This analysis simultaneously revealed a shift in IgG subclasses and Fc-glycosylation patterns in total and antigen-specific IgGs from different mouse cohorts. Eventually, Fc/2 characterization may reveal other protein modifications including oxidation, amino acid exchanges, and C-terminal lysine as demonstrated for monoclonal IgGs, which may be implemented for quality control of functional antibodies.
Drone-derived canopy height predicts biomass across non-forest ecosystems globally
Authors: Cunliffe A.M. , Anderson K. , Boschetti F. , Brazier R.E. , Graham H.A. , Myers-Smith I.H. , Astor T. , Boer M.M. , Calvo L. , Clark P.E. , Cramer M.D. , Encinas-Lara M.S. , Escarzaga S.M. , Fernández-Guisuraga J.M. , Fisher A.G. , Gdulová K. , Gillespie B.M. , Griebel A. , Hanan N.P. , Hanggito M.S. , Haselberger S. , Havrilla C.A. , Heilman P. , Ji W. , Karl J.W. , Kirchhoff M. , Kraushaar S. , Lyons M.B. , Marzolff I. , Mauritz M.E. , McIntire C.D. , Metzen D. , Méndez-Barroso L.A. , Power S.C. , Prošek J. , Sanz-Ablanedo E. , Sauer K.J. , Schulze-Brüninghoff D. , Šímová P. , Sitch S. , Smit J.L. , Steele C.M. , Suárez-Seoane S. , Vargas S.A. , Villarreal M.L. , Visser F. , Wachendorf M. , Wirnsberger H. , Wojcikiewicz R.
Published: July 2020

Non-forest ecosystems, dominated by shrubs, grasses and herbaceous plants, provide ecosystem services including carbon sequestration and forage for grazing, yet are highly sensitive to climatic changes. Yet these ecosystems are poorly represented in remotely-sensed biomass products and are undersampled byin-situmonitoring. Current global change threats emphasise the need for new tools to capture biomass change in non-forest ecosystems at appropriate scales. Here we assess whether canopy height inferred from drone photogrammetry allows the estimation of aboveground biomass (AGB) across low-stature plant species sampled through a global site network. We found mean canopy height is strongly predictive of AGB across species, demonstrating standardised photogrammetric approaches are generalisable across growth forms and environmental settings. Biomass per-unit-of-height was similarwithin, but differentamong, plant functional types. We find drone-based photogrammetry allows for monitoring of AGB across large spatial extents and can advance understanding of understudied and vulnerable non-forested ecosystems across the globe.
Financial strain and stressful social environment drive depressive symptoms, whileFKBP5variant intensifies the effect, in African Americans living in Tallahassee
Authors: Fuller Kia , Gravlee Clarence C. , McCarty Chris , Mitchell Miaisha M. , Mulligan Connie J.
Published: July 2020

The World Health Organization estimates that almost 300 million people suffer from depression worldwide. Depression is the most common mental health disorder and shows racial disparities in disease prevalence, age of onset, severity of symptoms, frequency of diagnosis, and treatment utilization across the United States. Since depression has both social and genetic risk factors, we propose a conceptual model wherein social stressors are primary risk factors for depression, but genetic variants increase or decrease individual susceptibility to the effects of the social stressors. Our research strategy incorporates both social and genetic data to investigate variation in symptoms of depression (CES-D scores). We collected data on financial strain (difficulty paying bills) and personal social networks (a model of an individual’s social environment), and we genotyped genetic variants in five genes involved in stress reactivity (HTR1a, BDNF, GNB3, SLC6A4, andFKBP5) in 135 African Americans residing in Tallahassee, Florida. We found that high financial strain and a high percentage of people in one’s social network who are a source of stress or worry were significantly associated with higher CES-D scores and explained more variation in CES-D scores than did genetic factors. Only one genetic variant (rs1360780 inFKBP5) was significantly associated with CES-D scores and only when the social stressors were included in the model. Interestingly, the effect ofFKPB5appeared to be strongest in individuals with high financial strain such that participants with a T allele at rs1360780 inFKBP5and high financial strain had the highest mean CES-D scores in our study population. These results suggest that material disadvantage and a stressful social environment increases the risk of depression, but that individual-level genetic variation may increase susceptibility to the adverse health consequences of social stressors.
Insights from the reanalysis of high-throughput chemical genomics data forEscherichia coliK-12
Authors: Wu Peter I-Fan , Ross Curtis , Siegele Deborah A. , Hu James C.
Published: July 2020

Despite the demonstrated success of genome-wide genetic screens and chemical genomics studies at predicting functions for genes of unknown function or predicting new functions for well-characterized genes, their potential to provide insights into gene function hasn’t been fully explored. We systematically reanalyzed a published high-throughput phenotypic dataset for the model Gram-negative bacteriumEscherichia coliK-12. The availability of high-quality annotation sets allowed us to compare the power of different metrics for measuring phenotypic profile similarity to correctly infer gene function. We conclude that there is no single best method; the three metrics tested gave comparable results for most gene pairs. We also assessed how converting qualitative phenotypes to discrete, qualitative phenotypes affected the association between phenotype and function. Our results indicate that this approach may allow phenotypic data from different studies to be combined to produce a larger dataset that may reveal functional connections between genes not detected in individual studies.
EEG-based diagnostics of the auditory system using cochlear implant electrodes as sensors
Authors: Somers Ben , Long Christopher J. , Francart Tom
Published: July 2020

The cochlear implant is one of the most successful medical prostheses, allowing deaf and severely hearing-impaired persons to hear again by electrically stimulating the auditory nerve. A trained audiologist adjusts the stimulation settings for good speech understanding, known as “fitting” the implant. This process is based on subjective feedback from the user, making it time-consuming and challenging, especially in paediatric or communication-impaired populations. Furthermore, fittings only happen during infrequent sessions at a clinic, and therefore cannot take into account variable factors that affect the user’s hearing, such as physiological changes and different listening environments. Objective audiometry, in which brain responses evoked by auditory stimulation are collected and analysed, removes the need for active patient participation. However, recording of brain responses still requires expensive equipment that is cumbersome to use. An elegant solution is to record the neural signals using the implant itself. We demonstrate for the first time the recording of continuous electroencephalographic (EEG) signals from the implanted intracochlear electrode array in human subjects, using auditory evoked potentials originating from different brain regions. Furthermore, we show that the response morphologies and amplitudes depend crucially on the recording electrode configuration. The integration of an EEG system into cochlear implants paves the way towards chronic neuro-monitoring of hearing-impaired patients in their everyday environment, and neuro-steered hearing prostheses, which can autonomously adjust their output based on neural feedback.
The risk ofXylella fastidiosaoutbreaks will decrease in the Mediterranean olive-producing regions
Authors: Godefroid M. , Morente M. , Schartel T. , Cornara D. , Purcell A. , Gallego D. , Moreno A. , Pereira J.A. , Fereres A.
Published: July 2020

The bacteriumXylella fastidiosa(Xf) is a worldwide distributed invasive insect-borne plant pathogen, which causes lethal diseases to many economically-important crops including olives, citrus, almonds and grapes as well as numerous forest, ornamental, and uncultivated plants. The Mediterranean basin is the top supplier of olive oil with 93% of the world production and is consequently highly concerned about the recent invasion ofXfin Europe. Recently, bioeconomic models estimated putative losses induced by the spread ofXfacross the European olive-producing area ranging from 1.9 to 5.2 billion euros over 50 years; however, such models did not take into account the insect vectors, which constitute a key driver ofXfspread. In the present study, we used bioclimatic species distribution models to predict the current and future climate suitability of the Mediterranean area for the main efficient or putative transmitters ofXfto olive (i.e.Philaenus spumarius, Neophilaenus campestrisandAphrophora alni). An important part of the total extent of the Mediterranean olive-producing area, mainly situated in southern Spain, Turkey and Greece, is predicted as currently poorly suitable for these vector species. Moreover, models forecast that nearly the totality of the Mediterranean olive-producing regions will likely become climatically little suitable for these vectors by 2050 due to climate change. In Europe,Xfoutbreaks have occurred so far only in localities predicted as climatically suitable for these main vector species (e.g. the Apulia region of Italy) while the areas predicted as poorly suitable are still apparentlyXf-free, which suggests that climate tolerances of vectors might play a main role in shapingXfoutbreaks patterns. This pattern highlights the crucial necessity of accounting for vectors when assessing risk ofXfoutbreaks, and when considering vector-borne diseases in general. The risk maps presented here will have important practical application for the optimization of current and future strategies to controlXfin the Mediterranean region.
Sleep-learning Impairs Subsequent Awake-learning
Authors: Ruch Simon , Züst Marc Alain , Henke Katharina
Published: July 2020

Although we can learn new information while asleep, we cannot consciously remember the sleep-formed memories because learning occurred in an unconscious state. Here, we ask whether sleep-learning expedites the subsequent awake-learning of the same information. To answer this question, we reanalyzed data (Züst et al., 2019, Curr Biol) from napping participants, who learned new semantic associations between fake foreign-words and translation-words (guga-ship) while in slow-wave sleep. They retrieved sleep-formed associations unconsciously on an implicit memory test following awakening. Then, participants took five runs of paired-associative learning to probe carry-over effects of sleep-learning on awake-learning. Surprisingly, sleep-learning diminished awake-learning when participants learned semantic associations that were congruent to sleep-learned associations (guga-boat). Yet, learning associations that conflicted with sleep-learned associations (guga-coin) was unimpaired relative to learning new associations (resun-table; baseline). We speculate that the impeded wake-learning originated in a deficient synaptic downscaling and resulting synaptic saturation in neurons that were activated during both sleep-learning and awake-learning.
Experimental adaptation of dengue virus 1 toAedes albopictusmosquitoes byin vivoselection
Authors: Bellone Rachel , Lequime Sebastian , Jupille Henri , Göertz Giel P. , Aubry Fabien , Mousson Laurence , Piorkowski Géraldine , Yen Pei-Shi , Gabiane Gaelle , Vazeille Marie , Sakuntabhai Anavaj , Pijlman Gorben P. , de Lamballerie Xavier , Lambrechts Louis , Failloux Anna-Bella
Published: July 2020

In most of the world, Dengue virus (DENV) is mainly transmitted by the mosquitoAedes aegyptiwhile in Europe,Aedes albopictusis responsible for human DENV cases since 2010. Identifying mutations that make DENV more competent for transmission byAe. albopictuswill help to predict emergence of epidemic strains. Ten serial passagesin vivoinAe. albopictusled to select DENV-1 strains with greater infectivity for this vectorin vivoand in cultured mosquito cells. These changes were mediated by multiple adaptive mutations in the virus genome, including a mutation at position 10,418 in the DENV 3’UTR within an RNA stem-loop structure involved in subgenomic flavivirus RNA (sfRNA) production. Using reverse genetics, we showed that the 10,418 mutation alone does not confer a detectable increase in transmission efficiencyin vivo. These results reveal the complex adaptive landscape of DENV transmission by mosquitoes and emphasize the role of epistasis in shaping evolutionary trajectories of DENV variants.
Attention expedites target selection by prioritizing the neural processing of distractor features
Authors: Bartsch Mandy V. , Merkel Christian , Schoenfeld Mircea A. , Hopf Jens-Max
Published: July 2020

Whether doing the shopping, or driving the car – to navigate daily life, our brain has to rapidly identify relevant color signals among distracting ones. Despite a wealth of research, how color attention is dynamically adjusted is little understood. Previous studies suggest that the speed of feature attention depends on the time it takes to enhance the neural gain of cortical units tuned to the attended feature. To test this idea, we had human participants switch their attention on the fly between unpredicted target color alternatives, while recording the electroencephalographic brain response to probes matching the target, a non-target, or a distracting alternative target color. Paradoxically, we observed a temporally prioritized processing of distractor colors. A larger neural gain for the distractor followed by stronger attenuation expedited target identification. Our results suggest that dynamic adjustments of feature attention involve the temporally prioritized processing and elimination of distracting feature representations.