bluuebunny/crossref_metadata_2025 huggingface dataset:
A Preliminary Investigation of Deficits in Executive Functions of Adults With Attention Deficit Hyperactivity Disorder
Authors: Alaghband-rad Javad , Dashti Behnoosh , Tehranidoost Mehdi , Zargarinejad Ghazaleh , FarhadBeigi Parvaneh
Published: October 2020

Several studies over the past two decades have investigated the neuropsychological deficits in children with attention deficit hyperactivity disorder (ADHD), but much less has been done on adults. This study aimed to assess the deficits in executive functions of adults with ADHD, especially in the areas of attention, inhibition, impulsivity, and planning. Twenty-four adults (18 years and older) diagnosed with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria, and also assessed with Conners' Adult ADHD Rating Scale, participated in the study. Executive functions in cases were compared with 20 matched controls through the three instruments of Tower of London (TOL), Continuous Performance Test (CPT), and Stroop test. Performance of cases was weaker than that of the control group in TOL. The difference was significant in subsequent thinking time in most of the trials and number of movements only at level 2. In CPT, the adults with ADHD made more commission errors. In addition, the ADHD cases made more errors in the word card of the Stroop test, and the time they spent reading all three cards was significantly longer than that of the control group. Our study suggests that several deficits in executive functions related to ADHD persist into adulthood, such as impairments in planning time and set shifting, response inhibition, impulsivity, and visuolingual processing. However, simple (visual-motor processing) and sustained attention might improve with age.
Nursing Professional Practice Model
Authors: Al-Ruzzieh Majeda A. , Ayaad Omar
Published: October 2020

Professional practice model (PPM) is one of the initial steps toward nursing excellence and the main requirement to earn Magnet Recognition®. This article will describe the process of development, implementation, and evaluation of a PPM for nursing in a specialized cancer center in Jordan.
Retrospective Analysis of Factors Associated With a Revised Fall Prevention Bundle in Hospitalized Patients
Authors: Scheidenhelm Sandra , Astroth Kim Schafer , DeLong Karen , Starkey Cyndy , Wolfe David
Published: October 2020

OBJECTIVE

The study aims to describe factors associated and injuries sustained with inpatients who fell while hospitalized and identify the impact of a revised fall-prevention bundle.

BACKGROUND

Approximately 1 million falls occur in hospitals annually, accounting for approximately 70% of inpatient accidents. Inpatient falls can result in physical injury, increased patient mortality and morbidity, decreased quality of life, and increased length of stay and cost.

METHODS

We used a retrospective review of patient fall data for adult inpatients who fell while hospitalized.

RESULTS

After reeducation and implementation of all elements of a revised fall-prevention bundle, there were fewer falls per patient day. We identified additional characteristics indicating when patients were more likely to be injured in a fall.

CONCLUSIONS

A fall-prevention bundle is effective in decreasing inpatient falls and falls with injury. Raising awareness of additional factors may decrease risk of injuries during an inpatient fall.
Leadership in Nursing Excellence
Authors: Van Bogaert Peter , Van heusden Danny , Slootmans Stijn , Haegdorens Filip , Verspuy Martijn , Van Aken Paul , Schoeters Veerle , Gillis Katrin , Siebens Kaat , Goossens Eva , Hans Guy , Van der Straeten Johnny , Timmermans Olaf , Franck Erik
Published: October 2020

Improving work conditions and the provision of high-quality care and patient safety is an issue in European hospitals. Inspired by a US program for nursing excellence, Magnet Recognition®, a Belgian hospital shared their experiences by organizing a summer school in 2019 with nurses of 21 hospitals from 9 countries. This article explains the hospital's research program, the link between the journey and the content of the summer school, lessons learned, and the extent to which participants of European hospitals were interested in nursing excellence and Magnet® designation.
Enteral Feeding of Children on Noninvasive Respiratory Support: A Four-Center European Study*
Authors: Tume Lyvonne N. , Eveleens Renate D. , Mayordomo-Colunga Juan , López Jorge , Verbruggen Sascha C. A. T. , Fricaudet Marianne , Smith Clare , Garcia Cusco Mireia Garcia , Latten Lynne , Valla Frédéric V.
Published: October 2020

Objectives:

To explore enteral feeding practices and the achievement of energy targets in children on noninvasive respiratory support, in four European PICUs.

Design:

A four-center retrospective cohort study.

Setting:

Four PICUs: Bristol, United Kingdom; Lyon, France; Madrid, Spain; and Rotterdam, The Netherlands.

Patients:

Children in PICU who required acute noninvasive respiratory support in the first 7 days. The primary outcome was achievement of standardized kcal/goal.

Interventions:

None.

Measurements and Main Results:

A total of 325 children were included (Bristol 104; Lyon 99; Madrid 72; and Rotterdam 50). The median (interquartile range) age and weight were 3 months (1–16 mo) and 5 kg (4–10 mo), respectively, with 66% admitted with respiratory failure. There were large between-center variations in practices. Overall, 190/325 (58.5%) received noninvasive respiratory support in order to prevent intubation and 41.5% after extubation. The main modes of noninvasive respiratory support used were high-flow nasal cannula 43.6%, bilevel positive airway pressure 33.2%, and continuous positive airway pressure 21.2%. Most children (77.8%) were fed gastrically (48.4% continuously) and the median time to the first feed after noninvasive respiratory support initiation was 4 hours (interquartile range, 1–9 hr). The median percentage of time a child was nil per oral while on noninvasive respiratory support was 4 hours (2–13 hr). Overall, children received a median of 56% (25–82%) of their energy goals compared with a standardized target of 0.85 of the recommended dietary allowance. Patients receiving step-up noninvasive respiratory support (p = < 0.001), those on bilevel positive airway pressure or continuous positive airway pressure (compared with high-flow nasal cannula) (p = < 0.001), and those on continuous feeds (p = < 0.001) achieved significantly more of their kcal goal. Gastrointestinal complications varied from 4.8—20%, with the most common reported being vomiting in 54/325 (16.6%), other complications occurred in 40/325 (12.3%) children, but pulmonary aspiration was rare 5/325 (1.5%).

Conclusions:

Children on noninvasive respiratory support tolerated feeding well, with relatively few complications, but prospective trials are now required to determine the optimal timing and feeding method for these children.
Brief Report: Seroadaptive Behaviors Varied Among Geographically Diverse iPrEx Participants
Authors: Truong Hong-Ha M. , Mehrotra Megha L. , Grant Robert M. ,   for the iPrEx Study Team
Published: October 2020

Background:

Seroadaptive behaviors refer to a wide range of harm reduction practices to decrease HIV transmission risk. Effective implementation of seroadaptive behaviors is dependent on knowledge of one's own serostatus and that of one's sexual partners. Partner-level and environmental-level attributes may affect seroadaptation practices. We assessed factors associated with seroadaptive behaviors.

Methods:

Men who have sex with men and transgender women were recruited from an HIV pre-exposure prophylaxis clinical trial (iPrEx) with study sites in the US, Peru, Ecuador, Brazil, Thailand, and South Africa. Partnership-level data were collected at the baseline visit for the 3 most recent partners. Participants were considered to have practiced seroadaptive behaviors if: (1) they believed their partner to be HIV-negative, that is, serosorting; or (2) no condomless receptive sex occurred with an HIV-positive or unknown status partner, that is, seropositioning.

Results:

Of 2331 participants, 41% always practiced seroadaptive behaviors, 36% sometimes did, and 23% never did. Participants enrolled at study sites in the US (P < 0.001) and Peru/Ecuador (P < 0.001) were more likely to practice seroadaptive behaviors, whereas transgender women were less likely to do so (P < 0.001). Seroadaptive behaviors were more likely to occur in relationships with steady partners (P = 0.005) and emotionally close relationships (P = 0.013).

Conclusions:

Seroadaptive behaviors were more frequently observed among iPrEx participants from the US, Peru, and Ecuador study sites and among participants in relationships with partners who they were more committed to and felt emotionally close to. Our findings suggest that seroadaptive behaviors may be influenced by social norms that vary geographically and culturally.
Outcome after surgical stabilization of rib fractures versus nonoperative treatment in patients with multiple rib fractures and moderate to severe traumatic brain injury (CWIS-TBI)
Authors: Prins Jonne T.H. , Van Lieshout Esther M.M. , Ali-Osman Francis , Bauman Zachary M. , Caragounis Eva-Corina , Choi Jeff , Christie D. Benjamin , Cole Peter A. , DeVoe William B. , Doben Andrew R. , Eriksson Evert A. , Forrester Joseph D. , Fraser Douglas R. , Gontarz Brendan , Hardman Claire , Hyatt Daniel G. , Kaye Adam J. , Ko Huan-Jang , Leasia Kiara N. , Leon Stuart , Marasco Silvana F. , McNickle Allison G. , Nowack Timothy , Ogunleye Temi D. , Priya Prakash , Richman Aaron P. , Schlanser Victoria , Semon Gregory R. , Su Ying-Hao , Verhofstad Michael H.J. , Whitis Julie , Pieracci Fredric M. , Wijffels Mathieu M.E.
Published: October 2020

BACKGROUND

Outcomes after surgical stabilization of rib fractures (SSRF) have not been studied in patients with multiple rib fractures and traumatic brain injury (TBI). We hypothesized that SSRF, as compared with nonoperative management, is associated with favorable outcomes in patients with TBI.

METHODS

A multicenter, retrospective cohort study was performed in patients with rib fractures and TBI between January 2012 and July 2019. Patients who underwent SSRF were compared to those managed nonoperatively. The primary outcome was mechanical ventilation-free days. Secondary outcomes were intensive care unit length of stay and hospital length of stay, tracheostomy, occurrence of complications, neurologic outcome, and mortality. Patients were further stratified into moderate (GCS score, 9–12) and severe (GCS score, ≤8) TBI.

RESULTS

The study cohort consisted of 456 patients of which 111 (24.3%) underwent SSRF. The SSRF was performed at a median of 3 days, and SSRF-related complication rate was 3.6%. In multivariable analyses, there was no difference in mechanical ventilation-free days between the SSRF and nonoperative groups. The odds of developing pneumonia (odds ratio [OR], 0.59; 95% confidence interval [95% CI], 0.38–0.98; p = 0.043) and 30-day mortality (OR, 0.32; 95% CI, 0.11–0.91; p = 0.032) were significantly lower in the SSRF group. Patients with moderate TBI had similar outcome in both groups. In patients with severe TBI, the odds of 30-day mortality was significantly lower after SSRF (OR, 0.19; 95% CI, 0.04–0.88; p = 0.034).

CONCLUSION

In patients with multiple rib fractures and TBI, the mechanical ventilation-free days did not differ between the two treatment groups. In addition, SSRF was associated with a significantly lower risk of pneumonia and 30-day mortality. In patients with moderate TBI, outcome was similar. In patients with severe TBI a lower 30-day mortality was observed. There was a low SSRF-related complication risk. These data suggest a potential role for SSRF in select patients with TBI.

LEVEL OF EVIDENCE

Therapeutic, level IV.
Acute Kidney Injury in a Predominantly African American Cohort of Kidney Transplant Recipients With COVID-19 Infection
Authors: Shrivastava Pritika , Prashar Rohini , Khoury Nadeen , Patel Anita , Yeddula Sirisha , Kitajima Toshihiro , Nagai Shunji , Samaniego Milagros
Published: October 2020

Background.

Renal involvement in severe or critical acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is frequent. Acute kidney injury (AKI) in African American (AA) kidney transplant recipients (KTRs) with COVID-19 is not well described. We report our experience with a predominantly AA cohort (79%) of KTRs with COVID-19 infections in the Detroit Metropolitan area.

Methods.

In this retrospective, single-center study, we identified 39 KTRs who tested positive for SARS-CoV-2 between March 16 and April 25, 2020. Data from electronic medical records were retrieved and compared between KTRs without AKI and KTRs with AKI.

Results.

One patient was excluded due to delayed graft function. Final analysis of AKI in KTRs with proven COVID-19 was done on 38 patients of which 30 were AA (79%). AKI occurred in 71.1% of COVID-19 KTRs (n = 27), of whom 6 (22.2%) patients required HD. The incidence of AKI in our cohort was 71% (27/38). AKI rate among AA was 76.7% versus 50% in non-AA cohort (P = 0.195). In a univariate logistic regression analysis, AA race was not significantly associated with AKI odds ratio (3.4; CI, 0.68-17.4; P = 0.14). After risk adjustment by race, patients with diabetes showed a significantly higher risk of AKI (adjusted odds ratio, 19.85; CI, 1.65-58.66; P = 0.012). KTRs with AKI had more preexisting renin angiotensin aldosterone system inhibitor use than KTRs without AKI (P = 0.03).

Conclusions.

KTRs infected with SARS-CoV-2 have a high incidence of AKI, with associated increased morbidity and mortality. Although no racial differences in mortality were noted in our KTRs with AKI, we await data from registries to help elucidate this difference.
Early Changes in Kidney Transplant Immunosuppression Regimens During the COVID-19 Pandemic
Authors: Bae Sunjae , McAdams-DeMarco Mara A. , Massie Allan B. , Ahn JiYoon B. , Werbel William A. , Brennan Daniel C. , Lentine Krista L. , Durand Christine M. , Segev Dorry L.
Published: October 2020

Background.

Kidney transplant recipients have higher risk of infectious diseases due to their reliance on immunosuppression. During the current COVID-19 pandemic, some clinicians might have opted for less potent immunosuppressive agents to counterbalance the novel infectious risk. We conducted a nationwide study to characterize immunosuppression use and subsequent clinical outcomes during the first 5 months of COVID-19 pandemic in the United States.

Methods.

Using data from the Scientific Registry of Transplant Recipients, we studied all kidney-only recipients in the United States from January 1, 2017, to March 12, 2020 (“prepandemic” era; n = 64 849) and from March 13, 2020, to July 31, 2020 (“pandemic” era; n = 5035). We compared the use of lymphocyte-depleting agents (versus basiliximab or no induction) and maintenance steroids (versus steroid avoidance/withdrawal) in the pandemic era compared with the prepandemic era. Then, we compared early posttransplant outcomes by immunosuppression regimen during the pandemic era.

Results.

Recipients in the pandemic era were substantially less likely to receive lymphocyte-depleting induction agents compared with their prepandemic counterparts (aOR = 0.400.530.69); similar trends were found across subgroups of state-level COVID-19 incidence, donor type, and recipient age. However, lymphocyte-depleting induction agents were associated with decreased rejection during admission (aOR = 0.110.230.47) but not with increased mortality in the pandemic era (aHR = 0.130.471.66). On the other hand, the use of maintenance steroids versus early steroid withdrawal remained similar (aOR = 0.711.071.62).

Conclusions.

The use of lymphocyte-depleting induction agents has decreased in favor of basiliximab and no induction during the COVID-19 pandemic. However, this shift might have resulted in increases in rejection with no clear reductions in posttransplant mortality.
Clavispora santaluciae f.a., sp. nov., a novel ascomycetous yeast species isolated from grapes
Authors: Drumonde-Neves João , Čadež Neža , Reyes-Domínguez Yazmid , Gallmetzer Andreas , Schuller# Dorit , Lima Teresa , Pais Célia , Franco-Duarte Ricardo
Published: October 2020

During a study of yeast diversity in Azorean vineyards, four strains were isolated which were found to represent a novel yeast species based on the sequences of the internal transcribed spacer (ITS) region (ITS1-5.8S–ITS2) and of the D1/D2 domain of the large subunit (LSU) rRNA gene, together with their physiological characteristics. An additional strain isolated from Drosophila suzukii in Italy had identical D1/D2 sequences and very similar ITS regions (five nucleotide substitutions) to the Azorean strains. Phylogenetic analysis using sequences of the ITS region and D1/D2 domain showed that the five strains are closely related to Clavispora lusitaniae, although with 56 nucleotide differences in the D2 domain. Intraspecies variation revealed between two and five nucleotide differences, considering the five strains of Clavispora santaluciae. Some phenotypic discrepancies support the separation of the new species from their closely related ones, such as the inability to grow at temperatures above 35 °C, to produce acetic acid and the capacity to assimilate starch. Neither conjugations nor ascospore formation were observed in any of the strains. The name Clavispora santaluciae f.a., sp. nov., is proposed to accommodate the above noted five strains (holotype, CBS 16465T; MycoBank no., MB 835794).
Lost in translation: No effect of repeated optogenetic cortico-striatal stimulation on compulsivity in rats
Authors: de Oliveira Amanda R. , Reimer Adriano E. , Simandl Gregory J. , Nagrale Sumedh S. , Widge Alik S.
Published: October 2020

BACKGROUND

The orbitofrontal cortex-ventromedial striatum (OFC-VMS) circuitry is widely believed to drive compulsive behavior. Hyperactivating this pathway in inbred mice produces excessive and persistent self-grooming, which has been considered a model for human compulsivity. We aimed to replicate these findings in outbred rats, where there are few reliable compulsivity models.

METHODS

27 male Long-Evans rats implanted with optical-fibers into VMS and with opsins delivered into OFC received optical stimulation at parameters that produce OFC-VMS plasticity and compulsive grooming in mice. We then evaluated rats for compulsive self-grooming at six timepoints: before, during, immediately after and one hour after each stimulation, one and two weeks after the ending of a 6-day stimulation protocol. To further test for effects of OFC-VMS hyperstimulation, we ran animals in three standard compulsivity assays: marble burying, nestlet shredding, and operant attentional setshifting.

RESULTS

OFC-VMS stimulation did not increase self-grooming or induce significant changes in nestlet shredding, marble burying, or set-shifting in rats. Follow-on evoked potential studies verified that the mouse protocol did alter OFC-VMS synaptic weighting.

CONCLUSIONS

In sum, although physiological changes were observed in the OFC-VMS circuitry, we could not reproduce in a strongly powered study in rats a model of compulsive behavior previously reported in mice. If optogenetic effects on behavior do not reliably transfer between rodent species, this may have important implications for designing rodent-to-human translational pipelines.
Tracking changes in behavioural dynamics using prediction error
Authors: Lorimer Tom , Goodridge Rachel , Bock Antonia K. , Agarwal Vitul , Saberski Erik , Sugihara George , Rifkin Scott A.
Published: October 2020

Automated analysis of video can now generate extensive time series of pose and motion in freely-moving organisms. This requires new quantitative tools to characterize behavioural dynamics. For the model roundwormCaenorhabditis elegans, body pose can be accurately quantified from video as coordinates in a single low-dimensional space. We focus on this well-established case as an illustrative example and propose a method to reveal subtle variations in behaviour at high time resolution. Our data-driven method, based on empirical dynamic modeling, quantifies behavioural change as prediction error with respect to a time-delay-embedded ‘attractor’ of behavioural dynamics. Because this attractor is constructed from a user-specified reference data set, the approach can be tailored to specific behaviours of interest at the individual or group level. We validate the approach by detecting small changes in the movement dynamics ofC. elegansat the initiation and completion of delta turns. We then examine an escape response initiated by an aversive stimulus and find that the method can track return to baseline behaviour in individual worms and reveal variations in the escape response between worms. We suggest that this general approach – defining dynamic behaviours using reference attractors and quantifying dynamic changes using prediction error – may be of broad interest and relevance to behavioural researchers working with video-derived time series.
A cross-species drug discovery pipeline to identify and validate new treatments for osteosarcoma
Authors: Somarelli Jason A. , Rupprecht Gabrielle , Altunel Erdem , Flamant Etienne M. , Rao Sneha , Sivaraj Dharshan , Lazarides Alexander L. , Hoskinson Sarah M. , Sheth Maya U. , Cheng Serene , Kim So Young , Ware Kathryn E. , Agarwal Anika , Cullen Mark M. , Selmic Laura E. , Everitt Jeffrey I. , McCall Shannon J. , Eward Cindy , Eward William C. , Hsu S. David
Published: October 2020

Purpose

Osteosarcoma is a rare but aggressive bone cancer that occurs primarily in children. Like other rare cancers, treatment advances for osteosarcoma have stagnated, with little improvement in survival for the past several decades. Developing new treatments has been hampered by extensive genomic heterogeneity and limited access to patient samples to study the biology of this complex disease.

Experimental design

To overcome these barriers, we combined the power of comparative oncology with patient-derived models of cancer and high-throughput chemical screens in a cross-species drug discovery pipeline.

Results

Couplingin vitrohigh-throughput drug screens on low-passage and established cell lines within vivovalidation in patient-derived xenografts we identify the proteasome and CRM1 nuclear export pathways as therapeutic sensitivities in osteosarcoma, with dual inhibition of these pathways inducing synergistic cytotoxicity.

Conclusions

These collective efforts provide an experimental framework and set of new tools for osteosarcoma and other rare cancers to identify and study new therapeutic vulnerabilities.
Behavioral and brain signatures of substance use vulnerability in childhood
Authors: Rapuano Kristina M. , Rosenberg Monica D. , Maza Maria T. , Dennis Nicholas , Dorji Mila , Greene Abigail S. , Horien Corey , Scheinost Dustin , Constable R. Todd , Casey BJ
Published: October 2020

The prevalence of risky behavior such as substance use increases during adolescence; however, the neurobiological precursors to adolescent substance use remain unclear. Predictive modeling may complement previous work observing associations with known risk factors or substance use outcomes by developing generalizable models that predict early susceptibility. The aims of the current study were to identify and characterize behavioral and brain models of vulnerability to future substance use. Principal components analysis (PCA) of behavioral risk factors were used together with connectome-based predictive modeling (CPM) during rest and task-based functional imaging to generate predictive models in a large cohort of nine- and ten-year-olds enrolled in the Adolescent Brain & Cognitive Development (ABCD) study (NDA release 2.0.1). Dimensionality reduction (n=9,437) of behavioral measures associated with substance use identified two latent dimensions that explained the largest amount of variance: risk-seeking (PC1; e.g., curiosity to try substances) and familial factors (PC2; e.g., family history of substance use disorder). Using cross-validated regularized regression in a subset of data (Year 1 Fast Track data; n>1,500), functional connectivity during rest and task conditions (resting-state; monetary incentive delay task; stop signal task; emotional n-back task) significantly predicted individual differences in risk-seeking (PC1) in held-out participants (partial correlations between predicted and observed scores controlling for motion and number of frames [rp]: 0.07-0.21). By contrast, functional connectivity was a weak predictor of familial risk factors associated with substance use (PC2) (rp: 0.03-0.06). These results demonstrate a novel approach to understanding substance use vulnerability, which—together with mechanistic perspectives—may inform strategies aimed at early identification of risk for addiction.
Health Insurance Support on Maternal Health Care: Evidence from Survey Data in India
Authors: Ali Imtiyaz , Akhtar Saddaf Naaz , Chauhan Bal Govind , Malik Manzoor Ahmad , Singh Kapil Dev
Published: October 2020

Maternal healthcare financing is key to the smooth functioning of maternal health systems in a country. In India, maternal healthcare persists as a significant public health issue. Adequate health insurance could transform the utilization of maternal health care services to prevent maternal consequences. This paper aims to examine the health insurance policies that cover maternal health and their performance in India. The unit-level social consumption data on health by the National Sample Survey Organizations (NSSO), conducted in India (2017-18), is used. Bi-variate analysis, logistic regression, and propensity scoring matching (PSM) are used to evaluate the coverage of health insurance coverage on women’s maternal health care utilization. Our findings suggest that spending on health insurance can benefit pregnant women, especially among the poor, without financial stress. The study has also minimized the financial burden and prevent high-risk pregnancy-related complications and consequences. Also, there is a need for proactive and inclusive policy development by the Government of India to promote more health insurance schemes in the public and private sectors. This can bring down the risk of maternal mortality and also boost the Indian economy in terms of a better quality of life in the long run, and the way towards more just and more egalitarian societies.

Highlights

Around 14.1% of Indian women are covered with health insurance schemes.

Muslim women have the lowest health insurance coverage in India.

Women covered with health insurance schemes has showed significant contributor to the better utilization of full ANC and institutional delivery compared to uncovered women in India.

A proactive and inclusive policy development is needed by the Government of India to promote more for health insurance schemes better quality of life in the long run.
COVID-19’s unfortunate events in schools: mitigating classroom clusters in the context of variable transmission
Authors: Tupper P. , Colijn C.
Published: October 2020

Widespread school closures occurred during the COVID-19 pandemic. Because closures are costly and damaging, many jurisdictions have since reopened schools with control measures in place. Early evidence indicated that schools were low risk and children were unlikely to be very infectious, but it is becoming clear that children and youth can acquire and transmit COVID-19 in school settings and that transmission clusters and outbreaks can be large. We describe the contrasting literature on school transmission, and argue that the apparent discrepancy can be reconciled by heterogeneity, or “overdispersion” in transmission, with many exposures yielding little to no risk of onward transmission, but some unfortunate exposures causing sizeable onward transmission. In addition, respiratory viral loads are as high in children and youth as in adults, pre- and asymptomatic transmission occur, and the possibility of aerosol transmission has been established. We use a stochastic individual-based model to find the implications of these combined observations for cluster sizes and control measures. We consider both individual and environment/activity contributions to the transmission rate, as both are known to contribute to variability in transmission. We find that even small heterogeneities in these contributions result in highly variable transmission cluster sizes in the classroom setting, with clusters ranging from 1 to 20 individuals in a class of 25. None of the mitigation protocols we modeled, initiated by a positive test in a symptomatic individual, are able to prevent large transmission clusters unless the transmission rate is low (in which case large clusters do not occur in any case). Among the measures we modeled, only rapid universal monitoring (for example by regular, onsite, pooled testing) accomplished this prevention. We suggest approaches and the rationale for mitigating these “unfortunate events”, even if they are expected to be rare.
Aging Reduces EEG Markers of Recognition Despite Intact Performance: Implications for Forensic Memory Detection
Authors: Hellerstedt Robin , Moccia Arianna , Brunskill Chloe M. , Bowman Howard , Bergström Zara M.
Published: October 2020

ERP-based forensic memory detection is based on the logic that guilty suspects will hold incriminating knowledge about crimes they have committed, and therefore should show parietal ERP positivities related to recognition when presented with reminders of their crimes. We predicted that such forensic memory detection might however be inaccurate in older adults, because of changes to recognition-related brain activity that occurs with aging. We measured both ERPs and EEG oscillations associated with episodic old/new recognition and forensic memory detection in 30 younger (age < 30) and 30 older (age > 65) adults. EEG oscillations were included as a complementary measure which is less sensitive to temporal variability and component overlap than ERPs. In line with predictions, recognition-related parietal ERP positivities were significantly reduced in the older compared to younger group in both tasks, despite highly similar behavioural performance. We also observed ageing-related reductions in oscillatory markers of recognition in the forensic memory detection test, while the oscillatory effects associated with episodic recognition were similar across age groups. This pattern of results suggests that while both forensic memory detection and episodic recognition are accompanied by ageing-induced reductions in parietal ERP positivities, these reductions may be caused by non-overlapping mechanisms across the two tasks. Our findings suggest that EEG-based forensic memory detection tests are invalid in older populations, limiting their practical applications.
The possible anti-inflammatory activity of macrolide antibiotics in male albino rat models
Authors: Hamed Mohamed , Abdelmonem Esmail , Zayed Mahmoud , Shaban Sameh , Khashab Iman El , Abu-El-Azm Soheir
Published: October 2020

Recently, there has been increasing evidence on the use of macrolide antibiotics in treatment of chronic inflammatory diseases through mechanisms distinct from their antibacterial activity. The key desired effect lies somewhere between these two therapeutic potentials and has not been identified yet. The aim of the present study was to evaluate the anti-inflammatory activity of the macrolide antibiotic azithromycin in formaldehyde induced arthritis and carrageenan induced air pouch in albino rats in comparison to the anti-rheumatic drug meloxicam. Results of Formaldehyde induced arthritis revealed that pretreatment of animals with a single daily dose of either azithromycin (10, 20 and 40 mg/kg) or meloxicam (4 mg/kg) for 15 days produced a significant reduction in inflammation size. Histopathological study showed that Formaldehyde produced marked inflammatory cell infiltration, congestion of blood vessels and soft tissue edema which were attenuated by azithromycin in dose dependent manner. The radiological study revealed that azithromycin attenuates soft tissue edema, periarticular bone resorption, narrowing of joint spaces and joint deformities induced by formaldehyde. This effect was marked with 40mg/kg azithromycin pre-treatment. In carrageenan, induced air pouch, results demonstrate that group of animals pretreated with azithromycin (10, 20 and 40 mg/kg) or meloxicam (4 mg/kg) for 6 days significantly attenuated the mean increase in total leukocyte count in air pouch exudate. In conclusion, the present work showed that azithromycin has antiinflammatory activity in the models tested and suggests that it can exert therapeutics effects independent of its anti-bacterial activity. Also, the anti-inflammatory effect of azithromycin was potent and even comparable to that of meloxicam.
The data-index: an author-level metric that values impactful data and incentivises data sharing
Authors: Hood Amelia S C , Sutherland William J
Published: October 2020

Author-level metrics are a widely used measure of scientific success. The h-index, and its variants, measure publication output (number of publications) and impact (number of citations), and these are often used to allocate funding or jobs. Here we argue that the emphasis on publication output and impact hinders progress in the fields of ecology and evolution as it disincentivises two fundamental practices: generating long-term datasets and sharing data. We describe a new author-level metric, the data-index, which values dataset output and impact and promotes generating and sharing data as a result. It is designed to complement other metrics of scientific success, as scientific contributions are diverse and our value system should reflect that. Future work should focus on designing alternative metrics that value our wider merits, such as communicating our research, informing policy, mentoring other scientists, and providing open-access code and tools.
Partial epithelial-to-mesenchymal transition is prognostic and associates with Slug in head and neck cancer
Authors: Schinke Henrik , Pan Min , Akyol Merve , Zhou Jiefu , Kranz Gisela , Libl Darko , Simon Florian , Canis Martin , Baumeister Philipp , Gires Olivier
Published: October 2020

Therapy resistance leading to local recurrence and metastases remains highly problematic in head and neck squamous cell carcinomas (HNSCC). Single cell RNA-sequencing defined a partial epithelial-to-mesenchymal transition (p-EMT) signature associated with metastases in HNSCC. However, the prognostic value of the p-EMT signature and potential drivers of p-EMT in HNSCC remain unclear. Here, single sample scoring of molecular phenotypes (Singscoring) served to establish clinical p-EMT-Singscores that were significantly associated with nodal metastases and predicted overall survival in two independent HNSCC cohorts. p-EMT-Singscores correlated most strongly with EMT transcription factor (EMT-TF) Slug.In vitro, Slug promoted p-EMT, enhanced invasion, and resistance to irradiation. In patients, Slug protein levels in tumors predicted disease-free survival and its peripheral expression at the interphase to tumor-microenvironment was significantly increased in recurring patients. Thus, p-EMT represents a novel clinical risk-predictor that impacts on HNSCC patients’ outcome and is partly controlled by Slug.
nMAT3 is an essential maturase splicing factor required for holo-complex I biogenesis and embryo-development inArabidopsis thalianaplants
Authors: Shevtsov-Tal Sofia , Best Corinne , Matan Roei , Chandran Sam Aldrin , Brown Gregory G. , Ostersetzer-Biran Oren
Published: October 2020

Group II introns are large catalytic RNAs that are particularly prevalent in the organelles of terrestrial plants. In angiosperm mitochondria, group II introns reside in the coding-regions of many critical genes, and their excision is essential for respiratory-mediated functions. Canonical group II introns are self-splicing and mobile genetic elements, consisting of the catalytic intron-RNA and its cognate intron-encoded endonuclease factor (i.e.maturase, Pfam-PF01348). Plant organellar introns are extremely degenerate, and lack many regions that are critical for splicing, including their related maturase-ORFs. The high degeneracy of plant mitochondrial introns was accompanied during evolution by the acquisition of ‘host-acting’ protein cofactors. These include several nuclear encoded maturases (nMATs) and various other splicing-cofactors that belong to a diverse set of RNA-binding families,e.g.RNA helicases (Pfam-PF00910), Mitochondrial Transcription Termination Factors (mTERF, Pfam-PF02536), Plant Organelle RNA Recognition (PORR, Pfam-PF11955), and Pentatricopeptide repeat (PPR, Pfam-PF13812) proteins. Previously, we established the roles of MatR and three nuclear-maturases, nMAT1, nMAT2, and nMAT4, in the splicing of different subsets of mitochondrial introns in Arabidopsis. The function of nMAT3 (AT5G04050) was found to be essential during early embryogenesis. Using a modified embryo-rescue method, we show thatnMAT3-knockout plants are strongly affected in the splicing ofnad1introns i1, i3 and i4 in Arabidopsis mitochondria. The embryo-defect phenotype is tightly associated with complex I biogenesis defects. Functional complementation ofnMAT3restored the splicing defects and altered embryogenesis phenotypes associated with thenmat3mutant-line.
High-throughput transcriptomics and benchmark concentration modeling for potency ranking of per- and polyfluoroalkyl substances (PFAS) in exposed human liver cell spheroids
Authors: Reardon A.J.F. , Rowan-Carroll A. , Ferguson S.S. , Leingartner K. , Gagne R. , Kuo B. , Williams A. , Lorusso L. , Bourdon-Lacombe J.A. , Carrier R. , Moffat I. , Yauk C.L. , Atlas E.
Published: October 2020

Per- and polyfluoroalkyl substances (PFAS) are some of the most prominent organic contaminants in human blood. Although the toxicological implications from human exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are well established, data on lesser-understood PFAS are limited. New approach methodologies (NAMs) that apply bioinformatic tools to high-throughput data are being increasingly considered to inform risk assessment for data-poor chemicals. The aim of this investigation was to identify biological response potencies (i.e., benchmark concentrations: BMCs) following PFAS exposures to inform read-across for risk assessment of data-poor PFAS. Gene expression changes were measured in primary human liver cell microtissues (i.e., 3D spheroids) after 1-day and 10-day exposures to increasing concentrations of 23 PFAS. The cells were treated with four subgroups of PFAS: carboxylates (PFCAs), sulfonates (PFSAs), fluorotelomers, and sulfonamides. An established pipeline to identify differentially expressed genes and transcriptomic BMCs was applied. We found that both PFCAs and PFSAs exhibited a trend toward increased transcriptional changes with carbon chain-length. Specifically, longer-chain compounds (7 to 10 carbons) were more likely to induce changes in gene expression, and have lower transcriptional BMCs. The combined high-throughput transcriptomic and bioinformatic analyses supports the capability of NAMs to efficiently assess the effects of PFAS in liver microtissues. The data enable potency ranking of PFAS for human liver cell spheroid cytotoxicity and transcriptional changes, and assessment ofin vitrotranscriptomic points of departure. These data improve our understanding of the health effects of PFAS and will be used to inform read-across for human health risk assessment.
Evolution of diversity in metabolic strategies
Authors: Caetano R. A. , Ispolatov Y. , Doebeli M.
Published: October 2020

Understanding the origin and maintenance of biodiversity is a fundamental problem. Many theoretical approaches have been investigating ecological interactions, such as competition, as potential drivers of diversification. Classical consumer-resource models predict that the number of coexisting species should not exceed the number of distinct resources, a phenomenon known as the competitive exclusion principle. It has recently been argued that including physiological tradeoffs in consumer-resource models can lead to violations of this principle and to ecological coexistence of very high numbers of species. Here we show that these results crucially depend on the functional form of the tradeoff. We investigate the evolutionary dynamics of resource use constrained by tradeoffs and show that if the tradeoffs are non-linear, the system either does not diversify, or diversifies into a number of coexisting species that does not exceed the number of resources. In particular, very high diversity can only be observed for linear tradeoffs.
Clarifying the relationship between body size and extinction risk in amphibians by complete mapping of model space
Authors: Cardillo Marcel
Published: October 2020

In vertebrates, large body size is often a key diagnostic feature of species threatened with extinction. However, in amphibians the link between body size and extinction risk is highly uncertain, with previous studies suggesting positive, negative, u-shaped, or no relationship. Part of the reason for this uncertainty is “researcher degrees of freedom”: the subjectivity and selectivity in choices associated with model specification. Here I clarify the size – threat association in amphibians using Specification Curve Analysis, an analytical approach from the social sciences that attempts to minimize this problem by complete mapping of model space. I find strong support for prevailing negative associations between body size and threat status, the opposite of patterns typical in other vertebrates. This pattern is largely explained by smaller species having smaller geographic ranges, but smaller amphibian species also appear to lack some of the life-history advantages (e.g. higher reproductive output) that are often assumed to “protect” small species in other taxa. These results highlight the need for a renewed conservation focus on the smallest species of the world’s most threatened class of vertebrates, as aquatic habitats become increasingly degraded by human activity.
Cell-Type-Specific Decrease of the Intrinsic Excitability of Motor Cortical Pyramidal Neurons in Parkinsonism
Authors: Chen Liqiang , Daniels Samuel , Kim Yerim , Chu Hong-Yuan
Published: October 2020

The hypokinetic motor symptoms of Parkinson’s disease (PD) are closely linked with a decreased motor cortical output as a consequence of elevated basal ganglia inhibition. However, whether and how the loss of dopamine alters the cellular properties of motor cortical neurons in PD remains undefined. We induced parkinsonism in adult C57BL6 mice of both sexes by injecting neurotoxin, 6-hydroxydopamine, into the medial forebrain bundle. By usingex vivopatch-clamp recording and retrograde tracing approach, we found that the intrinsic excitability of pyramidal tract neurons (PTNs) in the motor cortical layer 5b was greatly decreased in parkinsonism; but the intratelencephalic neurons (ITNs) were not affected. The cell-type-specific intrinsic adaptations were associated with a depolarized threshold and broadened width of action potentials in PTNs. Moreover, the loss of midbrain dopaminergic neurons impaired the capability of M1 PTNs to sustain high-frequency firing, which could underlie their abnormal pattern of activity in the parkinsonian state. We also showed that the decreased excitability in parkinsonism was caused by an impaired function of both persistent sodium channels and the large conductance, Ca2+-activated K+channels. Acute activation of dopaminergic receptors failed to rescue the impaired intrinsic excitability of M1 PTNs in parkinsonian mice. Altogether, our data demonstrated a cell-type-specific decrease of the excitability of M1 pyramidal neurons in parkinsonism. Thus, intrinsic adaptations in the motor cortex, together with pathological basal ganglia inhibition, underlie the decreased motor cortical output in parkinsonian state and exacerbate parkinsonian motor deficits.

Significance statement

The degeneration of midbrain dopaminergic neurons in Parkinson’s disease remodels the connectivity and function of cortico–basal ganglia–thalamocortical network. However, whether and how dopaminergic degeneration and the associated basal ganglia dysfunction alter motor cortical circuitry remain undefined. We found that pyramidal neurons in the layer 5b of the primary motor cortex (M1) exhibit distinct adaptations in response to the loss of midbrain dopaminergic neurons, depending on their long-range projections. Besides the decreased thalamocortical synaptic excitation as proposed by the classical model of Parkinson’s pathophysiology, these results, for the first time, show novel cellular and molecular mechanisms underlying the abnormal motor cortical output in parkinsonism.
Auditory Decisions in the Supplementary Motor Area
Authors: Morán Isaac , Perez-Orive Javier , Melchor Jonathan , Figueroa Tonatiuh , Lemus Luis
Published: October 2020

In human speech and communication across various species, recognizing and categorizing sounds is fundamental for the selection of appropriate behaviors. But how does the brain decide which action to perform based on sounds? We explored whether the premotor supplementary motor area (SMA), responsible for linking sensory information to motor programs, also accounts for auditory-driven decision making. To this end, we trained two rhesus monkeys to discriminate between numerous naturalistic sounds and words learned as target (T) or non-target (nT) categories. We demonstrated that the neural population is organized differently during the auditory and the movement periods of the task, implying that it is performing different computations in each period. We found that SMA neurons perform acoustic-decision-related computations that transition from auditory to movement representations in this task. Our results suggest that the SMA integrates sensory information while listening to auditory stimuli in order to form categorical signals that drive behavior.
Structural and biochemical characterization of bifunctional XynA
Authors: Xie Wei , Yu Qi , Liu Yun , Cao Ruoting , Zhang Ruiqing , Wang Sidi , Zhan Ruoting , Liu Zhongqiu , Wang Kui , Wang Caiyan
Published: October 2020

Xylan and cellulose are the two major constituents in numerous types of lignocellulosic biomass, representing a promising resource for biofuels and other biobased industries. The efficient degradation of lignocellulose requires the synergistic actions of cellulase and xylanase. Thus, bifunctional enzyme incorporated xylanase/cellulase activity has attracted considerable attention since it has great cost savings potential. Recently, a novel GH10 family enzyme XynA identified fromBacillussp. is found to degrade both cellulose and xylan. To understand its molecular catalytic mechanism, here we first solve the crystal structure of XynA at 2.3 Å. XynA is characterized with a classic (α/β)8 TIM-barrel fold (GH10 domain) flanked by the flexible N-terminal domain and C-terminal domain. Circular dichroism, protein thermal shift and enzyme activity assays reveal that conserved residues Glu182 and Glu280 are both important for catalytic activities of XynA, which is verified by the crystal structure of XynA with E182A/E280A double mutant. Molecular docking studies of XynA with xylohexaose and cellohexaose as well as site-directed mutagenesis and enzyme activity assay demonstrat that Gln250 and His252 are indispensible to cellulase and bifunctional activity, separately. These results elucidate the structural and biochemical features of XynA, providing clues for further modification of XynA for industrial application.