bluuebunny/crossref_metadata_2025 huggingface dataset:
Degradation of Lon inCaulobacter crescentus
Authors: Barros Benjamin B , Mahmoud Samar A , Chien Peter , Zeinert Rilee D.
Published: June 2020

Protein degradation is an essential process in all organisms. This process is irreversible and energetically costly; therefore, protein destruction must be tightly controlled. While environmental stresses often lead to upregulation of proteases at the transcriptional level, little is known about post-translational control of these critical machines. In this study we show that inCaulobacter crescentuslevels of the Lon protease are controlled through proteolysis. Lon turnover requires active Lon and ClpAP proteases. We show that specific determinants dictate Lon stability with a key carboxy-terminal histidine residue driving recognition. Expression of stabilized Lon variants results in toxic levels of protease that deplete normal Lon substrates such as the replication initiator DnaA to lethally low levels. Taken together, this work demonstrates a feedback mechanism in which ClpAP and Lon collaborate to tune Lon proteolytic capacity for the cell.

Importance

Proteases are essential, but unrestrained activity can also kill cells by degrading essential proteins. The quality control protease Lon must degrade many misfolded and native substrates. We show that Lon is itself controlled through proteolysis and that bypassing this control results in toxic consequences for the cell.
Efficacy of cognitive behavioral therapy on non-motor symptoms and quality of life in Parkinson’s disease: A systematic review and meta-analysis
Authors: Luo Fangyi , Ye Mengfei , Lv Tingting , Hu Baiqi , Chen Jiaqi , Yan Junwei , Wang Anzhe , Chen Feng , He Ziyi , Ding Zhinan , Zhang Jian , Gao Hui , Qian Chao , Liu Zheng
Published: June 2020

Objective

The aim of this study was to perform a quantitative analysis to evaluate the efficacy of cognitive behavioral therapy (CBT) on non-motor symptoms and its impact on quality of life (QOL) in Parkinson’s disease (PD).

Methods

We searched for randomized controlled trials in three electronic databases. Twelve studies, including 358 patients with PD, met the inclusion criteria. We determined the pooled efficacy by standard mean differences and 95% confidence intervals, using I2 to reveal heterogeneity.

Results

The result showed CBT had a significant effect on depression [-0.94 (95% CI, -1.25 to -0.64, P < 0.001)] and anxiety [-0.78 (95% CI, -1.05 to -0.50, P < 0.001)]. Moderate effect sizes were noted with stress [-0.60 (95% CI, -1.06 to -0.14, P = 0.01)] and sleep disorders [-0.44 (95% CI, -0.74 to -0.15, P = 0.003)]. There was no evident impact of CBT on fatigue or QOL. We found an intervention period > 8 weeks was advantageous compared with < 8 weeks, and CBT intervention was more effective than CBT developmental therapy.

Conclusion

We found that CBT in patients with PD was an efficacious therapy for some non-motor symptoms in PD, but not efficacious for fatigue and QOL. These results suggest that CBT results in significant improvement in PD and should be used as a conventional clinical intervention.
Laboratory Testing Implications of Risk-Stratification and Management for Improving Clinical Outcomes of COVID-19 Patients
Authors: Liu Caidong , Wang Ziyu , Li Jie , Xiang Changgang , Wu Lingxiang , Wu Wei , Hou Weiye , Sun Huiling , Wang Youli , Nie Zhenling , Gao Yingdong , Zhang Ruisheng , Xia Xinyi , Wang Qianghu , Wang Shukui
Published: June 2020

The high mortality rate of COVID-19 patients is mainly caused by the progression from mild to critical illness. To identify the key laboratory indicators and stratify high-risk COVID-19 patients with progression to severe/critical illness, we compared 474 moderate patients and 74 severe/critical patients. The laboratory indicators, including lactate dehydrogenase (LDH), monocytes percentage, etc. were significantly higher in the severe/critical patients (P <0.001) and showed a noticeable change at about a week before the diagnosis. Based on these indicators, we constructed a risk-stratification model, which can accurately grade the severity of patients with COVID-19 (accuracy = 0.96, 95% CI: 0.94 - 0.989, sensitivity = 0.98, specificity = 0.84). Also, compared with non-COVID-19 viral pneumonia, we found that COVID-19 had weaker dysfunction to the heart, liver, and kidney. The prognostic model based on laboratory indicators could help to diagnose, monitor, and predict severity at an early stage to those patients with COVID-19.
Vascular brain pathology is more important than neurodegeneration in pathogenesis of pre-stroke cognitive impairment
Authors: Schellhorn T , Zucknick M , Askim T , Munthe-Kaas R , Ihle-Hansen H , Seljeseth YM , Knapskog AB , Næss H , Ellekjær H , Thingstad P , Wyller T Bruun , Saltvedt I , Beyer MK
Published: June 2020

Introduction

To better understand the development of post-stroke cognitive impairment,we explored the association between pre-stroke neuroimaging features and pre-stroke cognitive impairment and investigated possible gender differences. Few previous studies on this topic have been performed.

Methods

In this large prospective longitudinal multicenter brain-MRI cohort study, patients admitted to five stroke units at five different Norwegian hospitals were recruited as part of the Norwegian cognitive impairment after stroke study. Visual radiological assessment of small vessel disease and neurodegenerative changes were performed on brain MRI from 410 patients. Pre-stroke cognition was assessed using the Global Deterioration Scale.

Results

At least one pathological marker was found in 68% of the patients. The mean age (SD) of the patients with no pathological changes other than the acute stroke, was 70 (± 12.9) and 75 (± 10.2) years for those with pathological scans (p ≤ 0.001). Men were more likely to have at least one pathological brain MRI finding, lacunes, or pathological medial temporal lobe atrophy. The highest percentage of patients with a pathological pre-stroke GDS were found in the “cerebrovascular pathology” group (37.5%) and in the “mixed pathology”-group (44%). In these groups, both men and women had an increased risk of impaired pre-stroke cognition.

Conclusion

The majority of patients showed preexisting structural brain pathology. Cerebrovascular pathology was the dominating imaging finding associated with cognitive impairment, thus indicating that the pathogenesis of pre-stroke cognitive impairment might be driven more by small vessel disease (SVD) than neurodegenerative changes. Gender differences exists, with less pathology in women.
Crescentic Glomerulonephritis: What’s different in South Asia? - A Single Center Observational Cohort Study
Authors: Alexander Suceena , Yusuf Sabina , Rajan Gautham , John Elenjickal Elias , Roy Sanjeet , Annamalai VC , Thomas Athul , Eapen Jeethu Joseph , Valson Anna T. , David Vinoi George , Varughese Santosh
Published: June 2020

Background

The spectrum and outcomes of crescentic glomerulonephritis in South Asia is vastly different from that reported worldwide and there is a paucity of information.

Methods

It was an observational cohort study of renal biopsies done in the largest tertiary center in South India over a period of 10 years with ≥50% crescents on histology.

Results

A total of 8645 kidney biopsies were done at our center from January 2006 to December 2015, and 200 (2.31%) were crescentic glomerulonephritis. Patients were categorized into three etiological groups - anti-GBM (type I), immune complex (type II) and pauci-immune (type III). The most common was type II (96, 46.5%), followed by type III (73, 38%) and then type I (31, 15.5%). Female preponderance was seen across all three types. About half of all the three types presented with recent onset hypertension. Type II had the highest median proteinuria (4.2 (2.1-6) g/day, p=0.06) and the median eGFR was lowest in type I (5 (4-8) ml/min/1.73m2, p<0.001). Among type III, ANCA associated vasculitis (AAV) was seen only in about half of the patients. Nearly one third patients with type I was also positive for ANCA making them ‘double positive’. Severe glomerular insults like tuft necrosis and chronicity as evidenced by moderate to severe interstitial fibrosis was a predominant feature of type I.

Conclusions

ANCA negative vasculitis as well as double positive types are reported for the first time from South-Asia. Prevalence of ANCA negative vasculitis (type III subgroup) was much higher in our population. Renal survival was significantly worse in type I & III compared to type II. Types I/III, moderate to severe IFTA, presence of oliguria/anuria and increasing percentage of crescents in renal biopsy were significant predictors of dialysis dependence at index visit or of end stage kidney disease at follow-up in our cohort.
Oral insulin immunotherapy in children at risk for type 1 diabetes in a randomized trial
Authors: Assfalg Robin , Knoop Jan , Hoffman Kristi L. , Pfirrmann Markus , Zapardiel-Gonzalo Jose Maria , Hofelich Anna , Eugster Anne , Weigelt Marc , Matzke Claudia , Reinhardt Julia , Fuchs Yannick , Bunk Melanie , Weiss Andreas , Hippich Markus , Halfter Kathrin , Hauck Stefanie M. , Hasford Jörg , Petrosino Joseph F. , Achenbach Peter , Bonifacio Ezio , Ziegler Anette-Gabriele
Published: June 2020

Background

Oral administration of antigen can induce immunological tolerance. Insulin is a key autoantigen in childhood type 1 diabetes with insulin autoimmunity often appearing in the first years of life. Here, oral insulin was given as antigen-specific immunotherapy before the onset of autoimmunity in children from age 6 months to assess its safety and actions on immunity and the gut microbiome.

Methods

A phase I/II randomized controlled trial was performed in 44 islet autoantibody-negative children aged 6 months to 2 years with genetic risk for type 1 diabetes. Children were randomized 1:1 to daily oral insulin (7.5 mg with dose escalation to 67.5 mg) or placebo for 12 months. Primary outcome was safety and immune efficacy pre-specified as hypoglycemia and induction of antibody or T cell responses to insulin, respectively.

Results

Oral insulin was well tolerated with no changes in metabolic variables. Immune responses to insulin were observed in both children who received insulin (55%) and placebo (67%), and were modified by theINSULINgene. Among children with type 1 diabetes-susceptibleINSULINgenotype, antibody responses to insulin were more frequent in insulin-treated (cumulative response, 75.8%) as compared to placebo-treated children (18.2%;P=0.0085), and T cell responses to insulin were modified by treatment-independent inflammatory episodes. Changes in the microbiome were related toINSULINgenotype.

Conclusion

The study demonstrated that oral insulin immunotherapy in young genetically at-risk children was safe and engaged the adaptive immune system in anINSULINgenotype-dependent manner, and linked inflammatory episodes to the activation of insulin-responsive T cells.

Trial registration

Clinicaltrials.govNCT02547519

Funding

German Center for Diabetes Research (DZD e.V.), Juvenile Diabetes Research Foundation (JDRF, grant 1-SRA-2018-546-S-B), Federal Ministry of Education and Research (BMBF, grant FKZ01KX1818).
Simultaneous Detection and Mutation Surveillance of SARS-CoV-2 and co-infections of multiple respiratory viruses by Rapid field-deployable sequencing
Authors: Bi Chongwei , Ramos-Mandujano Gerardo , Hala Sharif , Xu Jinna , Mfarrej Sara , Tian Yeteng , Esteban Concepcion Rodriguez , Nuñez Delicado Estrella , Alofi Fadwa S. , Khogeer Asim , Hashem Anwar M. , Almontashiri Naif A.M. , Pain Arnab , Izpisua Belmonte Juan Carlos , Li Mo
Published: June 2020

Strategies for monitoring the COVID-19 infection are crucial for combating the pandemic. Here we describe a method for multiplex isothermal amplification-based sequencing and real-time analysis of multiple viral genomes. It can simultaneously detect SARS-CoV-2 and co-infecting respiratory viruses, and monitor mutations for up to 96 samples in real time. The method, termed NIRVANA for Nanopore sequencing of Isothermal Rapid Viral Amplification for Near real-time Analysis, showed high sensitivity and specificity for SARS-CoV-2 in 70 clinical samples. It also simultaneously detected other viral pathogens (e.g. influenza A) in clinical and municipal wastewater samples. It provides a rapid field-deployable solution of COVID-19 and cos-infection detection and surveillance of the evolution of pandemic strains.
The gender gap in adolescent mental health: a cross-national investigation of 566,827 adolescents across 73 countries
Authors: Campbell Olympia , Bann David , Patalay Praveetha
Published: June 2020

Mental ill-health is a leading cause of disease burden worldwide. While women suffer from greater levels of mental health disorders, it remains unclear whether this gender gap differs systematically across regions and/or countries, or across the different dimensions of mental health. We analysed 2018 data from 566,827 adolescents across 73 countries for 4 mental health outcomes: psychological distress, life satisfaction, eudaemonia, and hedonia. We examine average gender differences and distributions for each of these outcomes as well as country-level associations between each outcome and purported determinants at the country level: wealth (GDP per capita), inequality (Gini index), and societal indicators of gender inequality (GII, GGGI, and GSNI). We report four main results: 1) The gender gap in mental health in adolescence is largely ubiquitous cross-culturally, with girls having worse average mental health; 2) There is considerable cross-national heterogeneity in the size of the gender gap, with the direction reversed in a minority of countries; 3) Higher GDP per capita is associated with worse average mental health and a larger gender gap across all mental health outcomes; and 4) more gender equal countries have larger gender gaps, with better mental health in males associated with greater gender equality and inconsistent associations with different mental health outcomes in females. Taken together, our findings suggest that while the gender gap appears largely ubiquitous, its size differs considerably by region, country, and dimension of mental health. Findings point to the hitherto unrealised complex nature of gender disparities in mental health and possible incongruence between expectations and reality in high gender equal countries.
Structural and functional signatures of executive deficits after early use of cocaine depend upon route of administration
Authors: de la Fuente Alethia , Vignaga Sofía Schurmann , Prado Pilar , Figueras Rosario , Lizaso Lucia , Manes Facundo , Cetkovich Marcelo , Tagliazucchi Enzo , Torralva Teresa
Published: June 2020

Background

There is growing evidence linking cocaine consumption with a broad spectrum of neurocognitive deficits. Despite of evidence suggesting that the route of administration should be taken into account to assess the short and long term effects of cocaine consumption, to our knowledge no study to date has characterized clinically relevant neuropsychological variables along with physiological variables separately in populations of individuals with histories of smoked cocaine dependence (SCD) and insufflated cocaine hydrochloride dependence (ICD).

Methods

The present study examined a sample of (a) 25 participants who fulfilled criteria for SCD, (b) 22 participants who fulfilled criteria for ICD, and (c) 25 healthy controls matched by age, gender, education, and socioeconomic status. An exhaustive neuropsychological battery was used to assess different cognitive domains (attention, executive functions, fluid intelligence, memory, language and social cognition). We complemented this neuropsychological assessment with the acquisition and analysis of structural (MRI) and functional (fMRI) neuroimaging data.

Results

Different routes of administration led to equally different profiles of neurocognitive impairment, with the SCD group being specifically associated with deficits in attention and executive functions. Consistent with risk models, executive function-attention deficit is better explained for age and age onset of consumption initiation. SCD also presented reduced grey matter density relative to ICD in the bilateral caudate, a key area for executive functions and attention. Connectivity between left caudate and inferior frontal regions mediates performance-structure association.

Conclusions

Cocaine routes of administration are associated to a differential profile that may not be due direct effects of stimulant action but also driven by cognitive and biological differences in key executive functioning and attention areas. This point the critical importance of the routes of administration. This information could inform clinical management and should be taken into account in clinical research.
Improving effectiveness of different deep learning-based models for detecting COVID-19 from computed tomography (CT) images
Authors: Acar Erdi , Şahin Engin , Yılmaz İhsan
Published: June 2020

Computerized Tomography (CT) has a prognostic role in the early diagnosis of COVID-19 due to it gives both fast and accurate results. This is very important to help decision making of clinicians for quick isolation and appropriate patient treatment. In this study, we combine methods such as segmentation, data augmentation and the generative adversarial network (GAN) to improve the effectiveness of learning models. We obtain the best performance with 99% accuracy for lung segmentation. Using the above improvements we get the highest rates in terms of accuracy (99.8%), precision (99.8%), recall (99.8%), f1-score (99.8%) and roc acu (99.9979%) with deep learning methods in this paper. Also we compare popular deep learning-based frameworks such as VGG16, VGG19, Xception, ResNet50, ResNet50V2, DenseNet121, DenseNet169, InceptionV3 and InceptionResNetV2 for automatic COVID-19 classification. The DenseNet169 amongst deep convolutional neural networks achieves the best performance with 99.8% accuracy. The second-best learner is InceptionResNetV2 with accuracy of 99.65%. The third-best learner is Xception and InceptionV3 with accuracy of 99.60%.
A Risk Prediction and Clinical Guidance System for Evaluating Patients with Recurrent Infections
Authors: Rider Nicholas L. , Cahill Gina , Motazedi Tina , Wei Lei , Kurian Ashok , Noroski Lenora M. , Seeborg Filiz O. , Chinn Ivan K. , Roberts Kirk
Published: June 2020

Background

Primary immunodeficiency diseases represent an expanding set of heterogeneous conditions which are difficult to recognize clinically. Diagnostic rates outside of the newborn period have not changed appreciably. This concern underscores a need for novel methods of disease detection.

Objective

We built an artificial intelligence model to provide real-time risk assessment about primary immunodeficiency and to facilitate prescriptive analytics for initiating the most appropriate diagnostic work up. Our goal is to improve diagnostic rates for primary immunodeficiency and shorten time to diagnosis.

Methods

We extracted data from the Texas Children’s Hospital electronic health record on a large population of primary immunodeficiency patients (n = 1762) and age-matched set of controls (n = 1698). From the cohorts, clinically relevant prior probabilities were calculated enabling construction of a Bayesian network probabilistic model. Our model was constructed with clinical-immunology domain expertise, trained on a balanced cohort of 100 cases-controls and validated on an unseen balanced cohort of 150 cases-controls. Performance was measured by area under the receiver operator characteristic curve (AUROC).

Results

Our Bayesian network was accurate in classifying immunodeficiency patients from controls (AUROC = 0.945; p<0.0001) at a risk threshold of ≥6%. Additionally, the model was 89% accurate for categorizing validation cohort members into appropriate International Union of Immunological Societies diagnostic categories.

Conclusion

Artificial intelligence methods can classify risk for primary immunodeficiency and guide management. Our Bayesian network enables highly accurate, objective decision making about risk and guides the user towards the appropriate diagnostic evaluation for patients with recurrent infections.
Heterogeneity in risk, testing and outcome of COVID-19 across outbreak settings in the Greater Toronto Area, Canada: an observational study
Authors: Wang Linwei , Ma Huiting , Yiu Kristy C.Y. , Calzavara Andrew , Landsman David , Luong Linh , Chan Adrienne K. , Kustra Rafal , Kwong Jeffrey C , Boily Marie-Claude , Hwang Stephen , Straus Sharon , Baral Stefan D , Mishra Sharmistha
Published: June 2020

Background

We compared the risk of, testing for, and death following COVID-19 infection across three settings (long-term care homes (LTCH), shelters, the rest of the population) in the Greater Toronto Area (GTA), Canada.

Methods

We sourced person-level data from COVID-19 surveillance and reporting systems in Ontario, and examined settings with population-specific denominators (LTCH residents, shelters, and the rest of the population). We calculated cumulatively, the diagnosed cases per capita, proportion tested for COVID-19, daily and cumulative positivity, and case fatality proportion. We estimated the age- and sex-adjusted relative rate ratios for test positivity and case fatality using quasi-Poisson regression.

Results

Between 01/23/2020-05/25/2020, we observed a shift in the proportion of cases: from travel-related and into LTCH and shelters. Cumulatively, compared to the rest of the population, the number of diagnosed cases per 100,000 was 59-fold and 18-fold higher among LTCH and shelter residents, respectively. By 05/25/2020, 77.2% of LTCH residents compared to 2.4% of the rest of the population had been tested. After adjusting for age and sex, LTCH residents were 2.5 times (95% confidence interval (CI): 2.3-2.8) more likely to test positive. Case fatality was 26.3% (915/3485), 0.7% (3/402), and 3.6% (506/14133) among LTCH residents, shelter population, and others in the GTA, respectively. After adjusting for age and sex, case fatality was 1.4-fold (95%CI: 1.1-1.9) higher among LTCH residents than the rest of the population.

Interpretation

Heterogeneity across micro-epidemics among specific populations in specific settings may reflect underlying heterogeneity in transmission risks, necessitating setting-specific COVID-19 prevention and mitigation strategies.
Dynamics of psychological responses to Covid-19 in India: A longitudinal study
Authors: Gopal Anvita , Sharma Anupam Joya , Subramanyam Malavika Ambale
Published: June 2020

To curb the spread of the novel coronavirus, India announced a nationwide lockdown on 24th March 2020 for 21 days, later extended for a longer time. This long period of lockdown greatly disrupted routine life and likely affecting citizens’ psychological well-being. The psychological toll of the pandemic on Indians is documented. However, no study has assessed whether the psychological toll changed over time due to repeated extensions of the lockdown. We followed up 159 Indian adults during the first two months of the lockdown to assess any change in their anxiety, stress, and depressive symptoms. Multilevel linear regression models of repeated observations nested within individuals, adjusted for socio-demographic covariates, showed that anxiety (β=0.81, CI: 0.03, 1.60), stress (β=0.51, CI: 0.32, 0.70), and depressive symptoms (β=0.37, CI: 0.13, 0.60) increased over time during the lockdown. This increase was higher among women than men independent of covariates. Individual resilience was negatively associated with the psychological outcomes. This suggests that the state needs to address the current mental health impacts of a long-drawn out lockdown and its long-term sequelae. Disproportionate burden on women needs immediate attention. Sustainable change requires addressing the root causes driving the gender inequalities in psychological distress during such crises.
PSEUDOMONAS AERUGINOSAVOLATILOME CHARACTERISTICS AND ADAPTATIONS IN CHRONIC CYSTIC FIBROSIS LUNG INFECTIONS
Authors: Davis Trenton J. , Karanjia Ava V. , Bhebhe Charity N. , West Sarah B. , Richardson Matthew , Bean Heather D.
Published: June 2020

Pseudomonas aeruginosachronic lung infections in individuals with cystic fibrosis (CF) significantly reduce quality of life and increase morbidity and mortality. Tracking these infections is critical for monitoring patient health and informing treatments. We are working toward the development of novel breath-based biomarkers to track chronicP. aeruginosalung infectionsin situ. Using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS), we characterized thein vitrovolatile metabolomes (or volatilomes) of 81P. aeruginosaisolates collected from 17 CF patients over at least a five-year period of their chronic lung infections. We detected 539 volatiles produced by theP. aeruginosaisolates, 69 of which were core volatiles that were highly conserved. We found that each early infection isolate has a unique volatilome, and as infection progresses, the volatilomes of isolates from the same patient become increasingly dissimilar, to the point that these intra-patient isolates are no more similar to one another than to isolates from other patients. We observed that the size and chemical diversity ofP. aeruginosavolatilomes do not change over the course of chronic infections; however, the relative abundances of core hydrocarbons, alcohols, and aldehydes do change, and are correlated to changes in phenotypes associated with chronic infections. This study indicates that it may be feasible to trackP. aeruginosachronic lung infections by measuring changes to the infection volatilome, and lays the groundwork for exploring the translatability of this approach to direct measurement using patient breath.

IMPORTANCE

Pseudomonas aeruginosais a leading cause of chronic lung infections in cystic fibrosis (CF), and are correlated with lung function declines. Significant clinical efforts are, therefore, aimed at detecting infections and tracking them for phenotypic changes, such as mucoidy and antibiotic resistance. Both the detection and tracking of lung infections relies on sputum cultures, but due to improvements in CF therapies, sputum production is declining though risks for lung infections persist. Therefore, we are working toward the development of breath-based diagnostics for CF lung infections. In this study we characterized of the volatile metabolomes of 81P. aeruginosaclinical isolates collected from 17 CF patients over a duration of at least five years of a chronic lung infection. We found that the volatilome ofP. aeruginosaadapts over time, and correlates to infection phenotype changes, suggesting it may be possible to track chronic CF lung infections with a breath test.
Ecological Specialization and Diversification in Birds
Authors: Crouch Nicholas M. A. , Ricklefs Robert E. , Igić Boris
Published: June 2020

Ecological specialization is widely thought to influence patterns of species richness by affecting rates at which species multiply and perish. Quantifying specialization is challenging, and using only one or a small number of ecological axes could bias estimates of overall specialization. Here, we calculate an index of specialization, based on seven measured traits, and estimate its effect on speciation and extinction rates in a large clade of birds. We find that speciation rate is independent of specialization, suggesting independence of local ecology and the geographic distributions of populations that promote allopatric species formation. Although some analyses suggest that more specialized species have higher extinction rates, leading to negative net diversification, this relationship is not consistently identified across our analyses. Our results suggest that specialization may drive diversification dynamics only on local scales or in specific clades, but is not generally responsible for macroevolutionary disparity in lineage diversification rates.
Auditory aversion in absolute pitch possessors
Authors: Rogenmoser Lars , Li H. Charles , Jäncke Lutz , Schlaug Gottfried
Published: June 2020

Absolute pitch (AP) refers to the ability of identifying the pitch of a given tone without reliance on any reference pitch. The downside of possessing AP may be the experience of disturbance when exposed to out-of-tune tones. Here, we investigated this so-far unexplored phenomenon in AP, which we refer to as auditory aversion. Electroencephalography (EEG) was recorded in a sample of AP possessors and matched control musicians without AP while letting them perform a task underlying a so-called affective priming paradigm: Participants judged valenced pictures preceded by musical primes as quickly and accurately as possible. The primes were bimodal, presented as tones in combination with visual notations that either matched or mismatched the actually presented tone. Regardless of the prime condition, AP possessors performed more poorly in judging pleasant pictures and their EEG revealed later peaks at around 200 ms (P200) after prime onset. Their performance dropped when responding to pleasant pictures preceded by incongruent primes, especially when mistuned by one semitone. This interference was also reflected in an EEG deflection at around 400 ms (N400) after picture onset, preceding the behavior responses. These findings suggest that AP possessors process mistuned musical stimuli and pleasant pictures as affectively unrelated with each other, supporting an aversion towards out-of-tune tones in AP possessors. The longer prime-related P200 latencies exhibited by AP possessors suggest a delay in integrating musical stimuli, underlying an altered affinity towards pitch-label associations.
The effect of heavy metals on thiocyanate biodegradation by an autotrophic microbial consortium enriched from mine tailings
Authors: Shafiei Farhad , Watts Mathew P. , Pajank Lukas , Moreau John W.
Published: June 2020

Bioremediation systems represent an environmentally sustainable approach to degrading industrially-generated thiocyanate (SCN-), with low energy demand and operational costs, and high efficiency and substrate specificity. However, heavy metals present in mine tailings effluent may hamper process efficiency by poisoning thiocyanate-degrading microbial consortia. Here we experimentally tested the tolerance of an autotrophic SCN--degrading bacterial consortium enriched from gold mine tailings for Zn, Cu, Ni, Cr, and As. All of the selected metals inhibited SCN-biodegradation to different extents, depending on concentration. At pH of 7.8 and 30°C, complete inhibition of SCN-biodegradation by Zn, Cu, Ni, and Cr occurred at 20, 5, 10, and 6 mg L-1, respectively. Lower concentrations of these metals decreased the rate of SCN-biodegradation, with relatively long lag times. Interestingly, the microbial consortium tolerated As even at 500 mg L-1, although both the rate and extent of SCN-biodegradation were affected. This study highlights the importance of considering metal co-contamination in bioreactor design and operation for SCN-bioremediation at mine sites.

Key points

Both the efficiency and rate of SCN-biodegradation were inhibited by heavy metals, to different degrees depending on type and concentration of metal

The autotrophic microbial consortium was capable of tolerating high levels of As
Specific ZNF274 binding interference at SNORD116 activates the maternal transcripts in Prader-Willi syndrome neurons
Authors: Langouët Maéva , Gorka Dea , Orniacki Clarisse , Dupont-Thibert Clémence M , Chung Michael S , Glatt-Deeley Heather R , Germain Noelle , Crandall Leann J , Cotney Justin L , Stoddard Christopher E , Lalande Marc , Chamberlain Stormy J
Published: June 2020

Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia, developmental delay, and hyperphagia/obesity. This disorder is caused by the absence of paternally-expressed gene products from chromosome 15q11-q13. We previously demonstrated that knocking out ZNF274, a KRAB-domain zinc finger protein capable of recruiting epigenetic machinery to deposit the H3K9me3 repressive histone modification, can activate expression from the normally silent maternal allele of SNORD116 in neurons derived from PWS iPSCs. However, ZNF274 has many other targets in the genome in addition to SNORD116. Depleting ZNF274 will surely affect the expression of other important genes and disrupt other pathways. Here we used CRISPR/Cas9 to delete ZNF274 binding sites at the SNORD116 locus to determine whether activation of the maternal copy of SNORD116 could be achieved without altering ZNF274 protein levels. We obtained similar activation of gene expression from the normally silenced maternal allele in neurons derived from PWS iPSCs, compared to ZNF274 knockout, demonstrating that ZNF274 is directly involved in the repression of SNORD116. These results suggest that interfering with ZNF274 binding at the maternal SNORD116 locus is a potential therapeutic strategy for PWS.
Receptor utilization of angiotensin converting enzyme 2 (ACE2) indicates a narrower host range of SARS-CoV-2 than that of SARS-CoV
Authors: Qiu Ye , Wang Qiong , Li Jin-Yan , Liao Ce-Heng , Zhou Zhi-Jian , Ge Xing-Yi
Published: June 2020

Coronavirus pandemics have become a huge threat to the public health worldwide in the recent decades. Typically, SARS-CoV caused SARS pandemic in 2003 and SARS-CoV-2 caused the COVID-19 pandemic recently. Both viruses have been reported to originate from bats. Thus, direct or indirect interspecies transmission from bats to humans is required for the viruses to cause pandemics. Receptor utilization is a key factor determining the host range of viruses which is critical to the interspecies transmission. Angiotensin converting enzyme 2 (ACE2) is the receptor of both SARS-CoV and SARS-CoV-2, but only ACE2s of certain animals can be utilized by the viruses. Here, we employed pseudovirus cell-entry assay to evaluate the receptor-utilizing capability of ACE2s of 20 animals by the two viruses and found that SARS-CoV-2 utilized less ACE2s than SARS-CoV, indicating a narrower host range of SARS-CoV-2. Meanwhile, pangolin CoV, another SARS-related coronavirus highly homologous to SARS-CoV-2 in its genome, yet showed similar ACE2 utilization profile with SARS-CoV rather than SARS-CoV-2. To clarify the mechanism underlying the receptor utilization, we compared the amino acid sequences of the 20 ACE2s and found 5 amino acid residues potentially critical for ACE2 utilization, including the N-terminal 20thand 42ndamino acids that may determine the different receptor utilization of SARS-CoV, SARS-CoV-2 and pangolin CoV. Our studies promote the understanding of receptor utilization of pandemic coronaviruses, potentially contributing to the virus tracing, intermediate host screening and epidemic prevention for pathogenic coronaviruses.
Reconciling Kinetic and Equilibrium Models of Bacterial Transcription
Authors: Morrison Muir , Razo-Mejia Manuel , Phillips Rob
Published: June 2020

The study of transcription remains one of the centerpieces of modern biology with implications in settings from development to metabolism to evolution to disease. Precision measurements using a host of different techniques including fluorescence and sequencing readouts have raised the bar for what it means to quantitatively understand transcriptional regulation. In particular our understanding of the simplest genetic circuit is sufficiently refined both experimentally and theoretically that it has become possible to carefully discriminate between different conceptual pictures of how this regulatory system works. This regulatory motif, originally posited by Jacob and Monod in the 1960s, consists of a single transcriptional repressor binding to a promoter site and inhibiting transcription. In this paper, we show how seven distinct models of this so-called simple-repression motif, based both on equilibrium and kinetic thinking, can be used to derive the predicted levels of gene expression and shed light on the often surprising past success of the equilibrium models. These different models are then invoked to confront a variety of different data on mean, variance and full gene expression distributions, illustrating the extent to which such models can and cannot be distinguished, and suggesting a two-state model with a distribution of burst sizes as the most potent of the seven for describing the simple-repression motif.
Global research trend in the treatment of the new Coronavirus diseases (COVID-19): bibliometric analysis
Authors: Mbogning Fonkou Maxime Descartes , Yacouba Abdourahamane
Published: June 2020

The Coronavirus 2019 (COVID-19) pandemic has caused worldwide concern and has become a major medical problem. Vaccines and therapeutics are important interventions for the management of this outbreak. This study aims to used bibliometric methods to identify research trends in the domain of therapeutics and vaccines to cure patients with COVID-19 since the beginning of the pandemic.

The Web of Science Core Collection database was retrieved for articles on therapeutic approaches to coronavirus disease management published between January 1, 2020 and May 20, 2020. Identified and analyzed the data included title, corresponding author, language, publication time, publication type, research focus.

A total of 1569 articles on coronavirus therapeutic means from 84 countries were published in 620 journals. We note the remarkable progressive increase in the number of publications related to research on therapies and vaccines for COVID-19. The United States provided the largest number of articles (405), followed by China (364). Journal of Medical Virology published most of them (n = 40). 1005 (64.05%) were articles, 286 (18.23%) were letters, 230 (14.66%) were reviews. The terms “COVID- 19” or “SARS-CoV-2” or “Coronavirus” or “hydroxychloroquine” or “chloroquine” or “2019-nCOV” or “ACE2” or “treatment” or “remdesivir” or “pneumonia” were most frequently used, as shown in the density visualization map. A network analysis based on keyword co-occurrence revealed five distinct types of studies: clinical, biological, epidemiological, pandemic management, and therapeutics (vaccines and treatments).

COVID-19 is a major disease that has had an impact on international public health at the global level. Several avenues for treatment and vaccines have been explored. Most of them focus on older drugs used to treat other diseases that have been effective for other types of coronaviruses. There is a discrepancy in the results obtained from the studies of the drugs included in this study. Randomized clinical trials are needed to evaluate older drugs and develop new treatment options.
Nearly Perfect Forecasting of the Total COVID-19 Cases in India: A Numerical Approach
Authors: Baruah Hemanta K.
Published: June 2020

There are standard computational and statistical techniques of forecasting the spread pattern of a pandemic. In this article, we are going to show how close the forecasts can be if we use a simple numerical approach that can be worked out using just a scientific calculator. Using a few recent data, short term forecasts can be found very easily. In this numerical technique, we need not make any assumptions, unlike in the cases of using computational and statistical methods. Such numerical forecasts would be nearly perfect unless the pandemic suddenly starts retarding during the period of the forecasts naturally or otherwise.
Delirium is a presenting symptom of COVID-19 in frail, older adults: a cohort study of 322 hospitalised and 535 community-based older adults
Authors: Zazzara Maria Beatrice , Penfold Rose S. , Roberts Amy L. , Lee Karla A. , Dooley Hannah , Sudre Carole H. , Welch Carly , Bowyer Ruth C. E. , Visconti Alessia , Mangino Massimo , Freydin Maxim B. , El-Sayed Moustafa Julia S. , Small Kerrin , Murray Benjamin , Modat Marc , Wolf Jonathan , Ourselin Sebastien , Martin Finbarr C. , Steves Claire J. , Lochlainn Mary Ni
Published: June 2020

Background

Frailty, increased vulnerability to physiological stressors, is associated with adverse outcomes. COVID-19 exhibits a more severe disease course in older, co-morbid adults. Awareness of atypical presentations is critical to facilitate early identification.

Objective

To assess how frailty affects presenting COVID-19 symptoms in older adults.

Design

Observational cohort study of hospitalised older patients and self-report data for community-based older adults.

Setting

Admissions to St Thomas’ Hospital, London with laboratory-confirmed COVID-19. Community-based data for 535 older adults using the COVID Symptom Study mobile application.

Subjects

Hospital cohort:patients aged 65 and over (n=322); unscheduled hospital admission between March 1st, 2020-May 5th, 2020; COVID-19 confirmed by RT-PCR of nasopharyngeal swab.Community-based cohort:participants aged 65 and over enrolled in the COVID Symptom Study (n=535); reported test-positive for COVID-19 from March 24th (application launch)-May 8th, 2020.

Methods

Multivariate logistic regression analysis performed on age-matched samples from hospital and community-based cohorts to ascertain association of frailty with symptoms of confirmed COVID-19.

Results

Hospital cohort:significantly higher prevalence of delirium in the frail sample, with no difference in fever or cough.Community-based cohort:significantly higher prevalence of probable delirium in frailer, older adults, and fatigue and shortness of breath.

Conclusions

This is the first study demonstrating higher prevalence of delirium as a COVID-19 symptom in older adults with frailty compared to other older adults. This emphasises need for systematic frailty assessment and screening for delirium in acutely ill older patients in hospital and community settings. Clinicians should suspect COVID-19 in frail adults with delirium.
Making a difference in multi-data-set crystallography: simple and deterministic data-scaling/selection methods
Authors: Assmann Greta M. , Wang Meitian , Diederichs Kay
Published: June 2020

Phasing by single-wavelength anomalous diffraction (SAD) from multiple crystallographic data sets can be particularly demanding because of the weak anomalous signal and possible non-isomorphism. The identification and exclusion of non-isomorphous data sets by suitable indicators is therefore indispensable. Here, simple and robust data-selection methods are described. A multi-dimensional scaling procedure is first used to identify data sets with large non-isomorphism relative to clusters of other data sets. Within each cluster that it identifies, further selection is based on the weighted ΔCC1/2, a quantity representing the influence of a set of reflections on the overall CC1/2 of the merged data. The anomalous signal is further improved by optimizing the scaling protocol. The success of iterating the selection and scaling steps was verified by substructure determination and subsequent structure solution. Three serial synchrotron crystallography (SSX) SAD test cases with hundreds of partial data sets and one test case with 62 complete data sets were analyzed. Structure solution was dramatically simplified with this procedure, and enabled solution of the structures after a few selection/scaling iterations. To explore the limits, the procedure was tested with much fewer data than originally required and could still solve the structure in several cases. In addition, an SSX data challenge, minimizing the number of (simulated) data sets necessary to solve the structure, was significantly underbid.
SDG 13 and the entwining of climate and sustainability metagovernance: an archaeological–genealogical analysis of goals-based climate governance
Authors: Charnock Robert , Hoskin Keith
Published: June 2020

Purpose

This paper brings insights from accounting scholarship to the measurement and reporting challenges of metagovernance approaches to sustainable development. Where scholarship on metagovernance—the combination of market, hierarchical and network governance—proposes deductive approaches to such challenges, we contend that a historically informed “abductive” approach offers valuable insight into therealpolitikof intergovernmental frameworks.

Design/methodology/approach

The paper adopts a Foucauldian “archaeological–genealogical” method to investigate the inclusion of climate change as a Sustainable Development Goal (SDG). It analyses more than 100 documents and texts, tracking the statement forms that crystallise prevailing truth claims across the development of climate and SDG metagovernance.

Findings

We show how the truth claims now enshrined in the Paris Agreement on Climate Change constrained the conceptualisation and operationalisation of SDG 13:Take urgent action to combat climate change and its impacts. The paper thereby reframes recent measurement and reporting challenges as outcomes of conceptual conflicts between the technicist emphasis of divisions within the United Nations and the truth claims enshrined in intergovernmental agreements.

Originality/value

This paper demonstrates how an archaeological–genealogical approach may start to address the measurement and reporting challenges facing climate and SDG metagovernance. It also highlights that the two degrees target on climate change has a manifest variability of interpretation and shows how this characteristic has become pivotal to operationalising climate metagovernance in a manner that respects the sovereignty of developing nations.
The short- and long-run drivers of lending behaviour by South African banks
Authors: Coetzee Johan , Genukile Lwazi
Published: June 2020

Purpose

The role of banks to efficiently allocate loans to borrowers is fundamental to a thriving economy. In South Africa this is particularly important, given a challenging socio-economic environment with high levels of unemployment and poor levels of economic growth. This paper investigates the short- and long-run determinants of bank lending behaviour for South African banks.

Design/methodology/approach

The study design uses time-series data in an autoregressive distributed-lagged model for the period 1994–2016.

Findings

The results indicate that factors such as the volume of deposits and the size of a bank are central to explaining bank lending behaviour in the short run, whereas GDP was found to be the only factor explaining lending behaviour in the long run.

Originality/value

The results suggest that the regulatory role of the South African Reserve Bank to ensure financial stability instils trust and certainty in the banking industry and is reflected in the short-run implications to ensure that large banks are stable and depositors avoid a run on a bank's deposits. This is particularly relevant if the long-run trajectory of the economy is one of sustainable economic growth. Furthermore, although the reserve bank is constantly under threat of not having a pro-growth policy agenda, the results support its role to promote confidence and trust through its financial stability policy. Should confidence in the financisal system not be present, it is argued that systemic risk will be exacerbated through the potential failure of large banks and depositors withdrawing their funds through a run on the bank in the short run. Where financial stability is present, market participants will be more inclined to make deposits into the large South African banks, given the trust and certainty within the system.