bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of Cigarette Smoking, Smokeless Tobacco Consumption, and Use of both forms in Adolescents in South Asia: A Secondary Analysis of the Global Youth Tobacco Surveys
Authors: Mishu Masuma Pervin , Siddiqui Faraz , Shukla Radha , Kanaan Mona , Dogar Omara , Siddiqi Kamran
Published: September 2020

Introduction

Tobacco uptake in adolescents is associated with a range of predictors. We examined the predictors of cigarette smoking, smokeless tobacco (ST) consumption, and use of both ST and cigarettes among adolescents in four South Asian countries.

Methods

We analyzed the Global Youth Tobacco Surveys (GYTS) data for Bangladesh (2013), India (2009), Pakistan (2013), and Sri Lanka (2015), using multinomial regression to examine associations between several predictors and tobacco use.

Results

Data from 23 681 adolescents were analyzed. Overall, 82.8% of the study population were between 13 and 15 years and 52.7% were girls, 2% were cigarette smokers, 6.5% were ST users, and 1.1% used both ST and cigarettes, in the past 30 days. Exposure to smoking in public places was associated with past 30-day smoking (relative risk ratio [RRR] 5.59, 95% confidence intervals [CI] 4.28–7.28), ST use (RRR 2.07, 95% CI 1.84–2.32), and use of both ST and cigarettes (RRR 11.42, 95% CI 7.44–17.54). Exposure to tobacco use in electronic media and being offered free tobacco products were associated with all forms of tobacco use. Shopkeepers’ refusal to sell cigarettes protected adolescents from smoking (RRR 0.47, 95% CI 0.36–0.63) and ST use (RRR 0.65, 95% CI 0.45–0.95). However, exposure to antitobacco mass media messages was not protective for any form of tobacco use. Adolescents taught at school about harmful effects of tobacco were less likely to use ST; no evidence of this association was observed for smoking.

Conclusion

The associations between tobacco use and protobacco factors were strong, but the associations with antitobacco factors lacked strength and consistency in this study population.

Implications

The predictors of adolescents using different tobacco products, crucial to inform and evaluate tobacco control efforts, are poorly understood. We investigated the associations between several environmental-level factors and cigarette smoking, ST consumption, and use of both forms among adolescents, whereas most of the previous studies focused on individual-level factors. Our study found strong associations between tobacco use and protobacco factors and lack of strength and consistency in associations between antitobacco factors and tobacco use in the study population. Our results indicate that the current tobacco control policies need strengthening to curb the tobacco epidemic in these countries.
Genetic incompatibilities and reduced transmission in chickens may limit the evolution of reassortants between H9N2 and panzootic H5N8 clade 2.3.4.4 avian influenza virus showing high virulence for mammals
Authors: Mostafa Ahmed , Blaurock Claudia , Scheibner David , Müller Christin , Blohm Ulrike , Schäfer Alexander , Gischke Marcel , Salaheldin Ahmed H , Nooh Hanaa Z , Ali Mohamed A , Breithaupt Angele , Mettenleiter Thomas C , Pleschka Stephan , Abdelwhab Elsayed M
Published: September 2020

The unprecedented spread of H5N8- and H9N2-subtype avian influenza virus (AIV) in birds across Asia, Europe, Africa, and North America poses a serious public health threat with a permanent risk of reassortment and the possible emergence of novel virus variants with high virulence in mammals. To gain information on this risk, we studied the potential for reassortment between two contemporary H9N2 and H5N8 viruses. While the replacement of the PB2, PA, and NS genes of highly pathogenic H5N8 by homologous segments from H9N2 produced infectious H5N8 progeny, PB1 and NP of H9N2 were not able to replace the respective segments from H5N8 due to residues outside the packaging region. Furthermore, exchange of the PB2, PA, and NS segments of H5N8 by those of H9N2 increased replication, polymerase activity and interferon antagonism of the H5N8 reassortants in human cells. Notably, H5N8 reassortants carrying the H9N2-subtype PB2 segment and to lesser extent the PA or NS segments showed remarkably increased virulence in mice as indicated by rapid onset of mortality, reduced mean time to death and increased body weight loss. Simultaneously, we observed that in chickens the H5N8 reassortants, particularly with the H9N2 NS segment, demonstrated significantly reduced transmission to co-housed chickens. Together, while the limited capacity for reassortment between co-circulating H9N2 and H5N8 viruses and the reduced bird-to-bird transmission of possible H5N8 reassortants in chickens may limit the evolution of such reassortant viruses, they show a higher replication potential in human cells and increased virulence in mammals.
The association of socioeconomic deprivation and paediatric open tibia fractures
Authors: Harrison William D. , Chan Yuen C. , James Leroy A. , Nayagam Selvadurai
Published: September 2020

The primary aim of this study is to test the association of open tibial fractures (OTF), in a paediatric age group, with socioeconomic deprivation. The secondary objectives are to more clearly define the epidemiological characteristics of these high-energy injuries. A consecutive series of patients with OTF presenting to a major trauma centre at a children’s hospital in Liverpool had age, gender, fracture pattern, mechanism, timing of the injury and their postcode of residence recorded. Those cases outside Liverpool, Sefton and Knowsley local authorities were excluded from incidence calculations. Postcodes were used to generate deprivation scores (Index of Multiple Deprivation, 2010) based on census data (2011). Cases were ranked and allocated to deprivation quintiles. A comparison to the normal population within Merseyside was undertaken using regression analysis. There were 71 cases over a 9-year period. Fifty cases resided within the geographical limits of Merseyside and were included in the incidence calculations. The annual incidence of paediatric OTF is 3.09 per 100 000 children (0–16 years). The median age at injury was 11 years (range 2–16) and this occurred most usually during term-time between 3 and 5 p.m. from road traffic collisions. Paediatric OTFs are strongly associated with socioeconomic deprivation. The association with deprivation reflects an exposure to unsafe roads in busy urban areas with limited access to safe playing spaces. Socioeconomically deprived men are most at risk from this injury. The links between deprivation and outcomes of treatment or long-term prospects are unclear.
Network meta-analysis of management of trigger thumb in children
Authors: Sirithiantong Todsaporn , Woratanarat Patarawan , Woratanarat Thira , Angsanuntsukh Chanika , Saisongcroh Tanyawat , Unwanatham Nattawut , Thakkinstian Ammarin
Published: September 2020

To estimate and rank cure and recurrence rates between conservative and operative treatments for trigger thumb in children. A systematic review was conducted by searching PubMed and Scopus. Eligible criteria were comparative studies included non-syndromic trigger thumbs, aged up to 10 years, reported at least 20 thumbs and followed up at least 12 months. Two assessors independently extracted data and appraised for cure, recurrence rates among observation, stretching, splinting, open surgery, and percutaneous surgery. We assessed the risk of bias in non-randomized studies of interventions. A network meta-analysis, and probability of being the best outcomes were estimated with surface under the cumulative ranking curves (SUCRA). From 6853 searched articles, eight studies (799 children and 981 thumbs) were included. Mean age was 1.87–2.83 years and average followed up time was 1–5.7 years. Open surgery, percutaneous release, splinting, and stretching had higher cure rate than observation; pooled risk ratio (95% confidence interval) of 2.06 (1.53–2.78), 1.79 (1.26–2.53), 1.76 (1.30–2.36), and 1.37 (0.93–2.03), respectively. Percutaneous release increased risk of recurrence 3.29 times (1.42–7.60) when compared with open surgery. The best cure rates were open surgery (SUCRA = 95) followed by splint (SUCRA = 63.4), and percutaneous technique (SUCRA= 62.8). The highest recurrence rates were percutaneous (SUCRA = 97.3), and open surgery (SUCRA = 62.4). Splint is the most appropriate intervention for pediatric trigger thumb. After failed conservative methods, open surgery is considered for operative treatment. Level of evidence: Therapeutic study level II–III.
Vaginal energy-based devices: characterization of adverse events based on the last decade of MAUDE safety reports
Authors: Wallace Shannon L. , Sokol Eric R. , Enemchukwu Ekene A.
Published: September 2020

Objectives:

Energy-based devices have gained momentum as minimally invasive procedures to treat both medical and cosmetic pelvic floor disorders including genitourinary syndrome of menopause, vaginal laxity, stress urinary incontinence, dyspareunia, and vulvar disorders such as lichen diseases and vestibulitis. However, the FDA recently issued a statement cautioning patients and providers that the safety and efficacy of energy-based devices for the treatment of vaginal symptoms has not been well established. Additionally, the FDA sent letters to the manufactures of energy-based devices with notifications that they could be violating the marketing standards of the FDA. The existing data on side effects is insufficient and limited to observational studies. We sought to characterize the safety events of vaginal energy-based devices by analysis of surveillance data from the FDA Manufacturer and User Facility Device Experience (MAUDE) database and specifically look at those events that occurred prior to the July 30, 2018 warning.

Methods:

The MAUDE database was queried between September 30, 2013 and October 31, 2019 for all vaginal energy-based devices. The incidence of safety events was reported for these devices and the most common complaints were described and characterized. Event reporting was analyzed before and after July 30, 2018.

Results:

Forty-two unique and relevant medical device reports (MDRs) were retrieved. The Mona Lisa Touch had the highest number of MDRs (40.5%) followed by ThermiVa (16.7%) and Viveve (14.2%). Each medical device report was associated with a single patient experience and within the 42 medical device reports, there were 85 complaints. A majority of the MDR complaints (52.9%) were also indications for energy-based devices procedures, which include vaginal pain, dyspareunia, lichen sclerosis, and urinary frequency. Two-thirds of the complaints (68.2%) were related to pain, but serious adverse events such as third-degree burns (3.5%) were rare. Most of the reportable events occurred before July 30, 2018 (83.3%), but most were reported after July 30, 2018 (78.6%).

Conclusions:

MAUDE-reported data suggests that the majority of patient complaints after vaginal energy-based device treatment include vaginal pain, bladder pain, and urinary symptoms. This study suggests that the majority of complaints are not severe, and some may be related to progression of the disease. The few severe adverse events reported in the MAUDE database may have contributed to the FDA warning regarding energy-based devices. Recall bias after the FDA warning, as well as the potential for litigation, may have prompted an increase in adverse event reporting after July 30, 2018.

Video Summary:

http://links.lww.com/MENO/A650.
Addressing Workplace Safety in the Emergency Department
Authors: Vrablik Marie C. , Lawrence Madelyn , Ray Jessica M. , Moore Megan , Wong Ambrose H.
Published: September 2020

Objective:

This study aims to identify interventions to address workplace violence in the emergency department based on direct evidence from experiences of patient assault.

Methods:

We performed de novo coding and thematic analysis of datasets from two geographically distinct institutions and five different sites that contained interviews with 80 health workers.

Results:

We identified concepts that corresponded to the micro (workers and patients), meso (organizations and clinical units), and macro (society at large, worldviews, and values) levels of the healthcare system. Within each level, potential interventions fell into the prevention, response, and recovery phases of emergency preparedness.

Conclusion:

Efforts to address workplace violence should consider interconnected influences from individual workers, organizations, and society at large. Comprehensive approaches at multiple phases of preparedness are needed to have sustained impact on safety.
Workers With Different Employment Status Have Different Exposures to Work Stressors and Different Responses to Identical Work Stressors
Authors: Park Jungsun , Kim Yangho
Published: September 2020

Introduction:

This study evaluated the relationship between exposure to diverse work-related stressors and psychological well-being in workers with precarious employment.

Methods:

This was a secondary analysis of data from the fifth Korean Working Conditions Survey, conducted in 2017.

Results:

Daily workers were more likely to report poor psychological well-being than regular or temporary workers. Furthermore, higher proportions of daily workers reported exposure to the nine analyzed work stressors. However, only three of nine workplace stressors (lack of decision latitude, lack of reward, and lack of support from workplace managers) affected male and female daily workers.

Conclusion:

A strategy designed to improve the psychological well-being of workers with precarious employment that is based on typical job stressor evaluation tools, may have limited effects.
Recurrent glomerulonephritis after renal transplantation
Authors: Chukwu Chukwuma A. , Middleton Rachael , Kalra Philip A.
Published: September 2020

Purpose of review

The current understanding of the incidence, predisposing factors, pathophysiology and effective treatment of recurrent glomerulonephritis (RGN) in renal transplants remains at best patchy and at worst, completely lacking. Current reports have been limited by inconsistencies in study design, sample populations and lengths of follow-up. Making sense of the available evidence will provide the tools to support transplant nephrologists in their management of allograft donors and recipients.

Recent findings

With better survival of renal allografts, RGN has become a dominant factor influencing allograft survival. Evidently, the risk of recurrence is proportional to the incremental time posttransplantation. The proposed risk factors for RGN include but are not limited to the severity of primary glomerulonephritis (PGN), younger recipient age, live-related donor allograft, minimal HLA mismatch, steroid avoidance and nonuse of induction therapy. Unfortunately, these findings are derived from retrospective cohort and registry studies; hence, true causality for RGN is hard to prove.

The management of RGN is improving, as we gain greater understanding of its pathophysiology, including the genetic, alloimmune and autoimmune contributions to recurrence. With better pretransplant risk stratification, posttransplant surveillance, novel biomarkers and new treatment strategies, we hope the transplant community will eventually have the tools to predict risk, prevent recurrence and personalise treatment of RGN.
GFR slope as a surrogate endpoint for CKD progression in clinical trials
Authors: Inker Lesley A. , Chaudhari Juhi
Published: September 2020

Purpose of review

There is a paucity of therapies for chronic kidney disease (CKD), in part because of the slow nature of the disease which poses challenges in selection of endpoints in randomized controlled trials (RCT). There is increasing evidence for the use of glomerular filtration rate (GFR)-based endpoints either as percentage decline using time-to-event analyses, or as difference in slope between treatment arms. We reviewed the rationale for using surrogate endpoints and optimal methods for their evaluation prior to their use and evidence for GFR-based endpoints and particularly GFR slope as validated surrogate endpoints and considerations for their use in RCTs.

Recent findings

In an individual patient meta-analysis of 47 studies (60 620 participants), treatment effects on the clinical endpoint were accurately predicted from treatment effects on 3-year total slope [median R
2 = 0.97 (95% Bayesian confidence interval (BCI), 0.78–1.00] and on the chronic slope [R
2 = 0.96 (95% BCI, 0.63–1.00)]. In a simulation study, GFR slope substantially reduced the required sample size and duration of follow-up compared to the clinical endpoint given high baseline GFR and absence of acute treatment effect. In the presence of acute effect, results were more complicated.

GFR decline is accepted, and GFR slope is being considered, by regulatory authorities as a validated surrogate endpoint for CKD RCTs.
VR and machine learning: novel pathways in surgical hands-on training
Authors: Veneziano Domenico , Cacciamani Giovanni , Rivas Juan Gomez , Marino Nicola , Somani Bhaskar K.
Published: September 2020

Purpose of review

Surgical training has dramatically changed over the last decade. It has become not only the way to prepare surgeons for their everyday work, but also a way to certify their skills thus increasing patient safety. This article reviews advances in the use of machine learning and artificial intelligence applied to virtual reality based surgical training over the last 5 years.

Recent findings

Eight articles have been published which met the inclusion criteria. This included six articles about the use of machine learning and artificial intelligence for assessment purposes and two articles about the possibility of teaching applications, including one review and one original research article. All the research articles pointed out the importance of machine learning and artificial intelligence for the stratification of trainees, based on their performance on basic tasks or procedures simulated in a virtual reality environment.

Machine learning and artificial intelligence are designed to analyse data and use them to take decisions that typically require human intelligence. Evidence in literature is still scarce about this technology applied to virtual reality and existing manuscripts are mainly focused on its potential to stratify surgical performance and provide synthetic feedbacks about it. In consideration of the exponential growth of computer calculation capabilities, it is possible to expect a parallel increase of research about this topic within the next few years.
Ethical Considerations of Social Media to Recruit Caregivers of Children With Cancer
Authors: Tan Kelly R. , Killela Mary K. , Leckey Jill
Published: September 2020

Background

Social media platforms are useful for recruiting hard-to-reach populations, such as caregivers of children with cancer, for research. However, there are unique ethical considerations in using social media.

Objectives

The aim of the study was to describe the methods used to recruit hard-to-reach caregivers (parents of children with cancer) for research and related ethical considerations.

Methods

We used The Belmont Report tenets (respect for persons, beneficence, and justice) as a guiding framework to identify issues relevant to social media recruitment of hard-to-reach populations and to describe how we addressed these issues in our study.

Results

We engaged leaders of two online communities that offer peer support for caregivers of children with cancer to help with recruitment to our study on financial effect of pediatric cancer. We identified issues in using social media for recruiting hard-to-reach populations in alignment with The Belmont Report, including risk for subject selection bias, privacy rights, protecting identity of participants, data security issues, and access to research. We addressed issues by deliberate study design decisions and engagement with online community advocates.

Discussion

Using social media to recruit hard-to-reach populations may be a successful way to engage them in research. Although researchers may remain compliant with the institutional review board of their facilities and are faithful to the tenets of The Belmont Report, unanticipated ethical issues may arise directly or indirectly as a result of using social media. This article identifies these issues and provides suggestions for dealing with them.
Biomarkers for Estimating Risk of Hospital Mortality and Long-Term Quality-of-Life Morbidity After Surviving Pediatric Septic Shock: A Secondary Analysis of the Life After Pediatric Sepsis Evaluation Investigation*
Authors: Wong Hector R. , Reeder Ron W. , Banks Russell , Berg Robert A. , Meert Kathleen L. , Hall Mark W. , McQuillen Patrick S. , Mourani Peter M. , Chima Ranjit S. , Sorenson Samuel , Varni James W. , McGalliard Julie , Zimmerman Jerry J.
Published: September 2020

Objectives:

The Life After Pediatric Sepsis Evaluation investigation recently reported that one-third of children who survive sepsis experience significant health-related quality-of-life impairment compared with baseline at 1 year after hospitalization. Pediatric Sepsis Biomarker Risk Model is a multibiomarker tool for estimating baseline risk of mortality among children with septic shock. We determined if the Pediatric Sepsis Biomarker Risk Model biomarkers have predictive capacity for estimating the risk of hospital mortality and long-term health-related quality-of-life morbidity among children with community-acquired septic shock.

Design:

Secondary analysis.

Setting:

Twelve academic PICUs.

Patients:

A subset of Life After Pediatric Sepsis Evaluation subjects (n = 173) with available blood samples.

Interventions:

None.

Measurements and Main Results:

Three predefined outcomes from the Life After Pediatric Sepsis Evaluation investigation were evaluated: all-cause hospital mortality (n = 173), and the composite outcome of mortality or persistent, serious deterioration of health-related quality of life (> 25% below baseline) among surviving children at 1 month (n = 125) or 3 months (n = 117). Pediatric Sepsis Biomarker Risk Model had an area under the receiver operating characteristic curve of 0.73 (95% CI, 0.59–0.87; p = 0.002) for estimating the risk of hospital mortality and was independently associated with increased odds of hospital mortality. In multivariable analyses, Pediatric Sepsis Biomarker Risk Model was not independently associated with increased odds of the composite outcome of mortality or deterioration of persistent, serious deterioration health-related quality of life greater than 25% below baseline. A new decision tree using the Pediatric Sepsis Biomarker Risk Model biomarkers had an area under the receiver operating characteristic curve of 0.87 (95% CI, 0.80–0.95) for estimating the risk of persistent, serious deterioration health-related quality of life at 3 months among children who survived septic shock.

Conclusions:

Pediatric Sepsis Biomarker Risk Model had modest performance for estimating hospital mortality in an external cohort of children with community-acquired septic shock. The Pediatric Sepsis Biomarker Risk Model biomarkers appear to have utility for estimating the risk of persistent, serious deterioration of health-related quality of life up to 3 months after surviving septic shock. These findings suggest an opportunity to develop a clinical tool for early assignment of risk for long-term health-related quality-of-life morbidity among children who survive septic shock.
A Quality Improvement Approach to Reduce Unplanned Extubation in the NICU While Avoiding Sedation and Restraints
Authors: Bertoni C. Briana , Bartman Thomas , Ryshen Gregory , Kuehne Brandon , Larouere Marissa , Thomas Leslie , Wishloff Erin , Shepherd Edward , Dillard Julie , Pavlek Leeann R. , Moallem Mohannad
Published: September 2020

Introduction:

The unplanned extubation (UE), a common adverse event in the neonatal intensive care unit (NICU), may result in airway trauma, cardiopulmonary resuscitation, and, in extreme cases, death. As part of the Nationwide Children’s Hospital NICU’s effort to optimize NICU graduates’ neurodevelopmental outcomes, skin-to-skin care of intubated infants is encouraged, while sedation and restraints to prevent UE are strongly discouraged. This project aimed to decrease the UE rate from 1.85 to 1.5 per 100 endotracheal tube (ETT) days.

Methods:

The project occurred in a 114-bed, level-IV NICU with approximately 850 admissions per year and 100% outborn infants. A multidisciplinary team began biweekly meetings to review all UE events, later separating these into preventable and nonpreventable. Important ongoing tests of change included assigning a single process owner for UE reporting, ensuring proper ETT securement, and using 2 clinical staff during patient and/or ETT manipulation.

Results:

Early in the project, enhanced detection led to an increased rate from 1.85 to 3.26 per 100 ETT days. However, identifying preventable events empowered staff to decrease the frequency to 2.03 per 100 ETT days. In August 2017, an ETT taping method change produced an increase in special causes due to decreased compliance. However, when securement methods were enhanced, noncompliance reversed and is now trending favorably.

Conclusions:

Decreasing UE in a neurodevelopmentally friendly unit, which avoids sedation and restraints, is challenging. Using a multidisciplinary quality improvement approach and after appropriately capturing events, we reduced UE, with the highest impact of intervention being ETT securement standardization.
HIV Stigma and Viral Suppression Among People Living With HIV in the Context of Universal Test and Treat: Analysis of Data From the HPTN 071 (PopART) Trial in Zambia and South Africa
Authors: Hargreaves James R. , Pliakas Triantafyllos , Hoddinott Graeme , Mainga Tila , Mubekapi-Musadaidzwa Constance , Donnell Deborah , Piwowar-Manning Estelle , Agyei Yaw , Mandla Nomhle F. , Dunbar Rory , Macleod David , Floyd Sian , Bock Peter , Fidler Sarah , Hayes Richard J. , Seeley Janet , Stangl Anne , Bond Virginia , Ayles Helen ,   on behalf of the HPTN 071 (PopART) Study Team
Published: September 2020

Background:

The impact of HIV stigma on viral suppression among people living with HIV (PLHIV) is not well characterized.

Setting:

Twenty-one communities in Zambia and South Africa, nested within the HPTN 071 (PopART) trial.

Methods:

We analyzed data on viral suppression (<400 copies HIV RNA/mL) among 5662 laboratory-confirmed PLHIV aged 18–44 years who were randomly sampled within the PopART trial population cohort 24 months after enrolment (PC24). We collected data on experiences and internalization of stigma from those PLHIV who self-reported their HIV status (n = 3963/5662) and data on perceptions of stigma from a 20% random sample of all PLHIV (n = 1154/5662). We also measured stigma at the community-level among PLHIV, community members, and health workers. We analyzed the association between individual- and community-level measures of HIV stigma and viral suppression among PLHIV, adjusting for confounding.

Results:

Of all 5662 PLHIV, 69.1% were virally suppressed at PC24. Viral suppression was highest among those 3963 cohort participants who self-reported living with HIV and were on ART (88.3%), and lower among those not on treatment (37.5%). Self-identifying PLHIV who reported internalized stigma were less likely to be virally suppressed (75.0%) than those who did not (80.7%; adjusted risk ratio, 0.94 95% CI: 0.89 to 0.98). Experiences, perceptions, and community-level measures of stigma were not associated with viral suppression.

Conclusion:

Internalized stigma among PLHIV was associated with a lower level of viral suppression; other dimensions of stigma were not. Stigma reduction approaches that address internalized stigma should be an integral component of efforts to control the HIV epidemic.
The influence of the cross-modal emotional pre-preparation effect on audiovisual integration
Authors: Zhao Zhang , Lei Sun , Weiqi He , Suyong Yang , Wenbo Luo
Published: September 2020

Previous studies have shown that the cross-modal pre-preparation effect is an important factor for audiovisual integration. However, the facilitating influence of the pre-preparation effect on the integration of emotional cues remains unclear. Therefore, this study examined the emotional pre-preparation effect during the multistage process of audiovisual integration. Event-related potentials (ERPs) were recorded while participants performed a synchronous or asynchronous integration task with fearful or neutral stimuli. The results indicated that, compared with the sum of the unisensory presentation of visual (V) and auditory (A) stimuli (A+V), only fearful audiovisual stimuli induced a decreased N1 and an enhanced P2; this was not found for the neutral stimuli. Moreover, the fearful stimuli triggered a larger P2 than the neutral stimuli in the audiovisual condition, but not in the sum of the combined (A+V) waveforms. Our findings imply that, in the early perceptual processing stage and perceptual fine processing stage, fear improves the processing efficiency of the emotional audiovisual integration. In the last cognitively assessing stage, the fearful audiovisual induced a larger late positive component (LPC) than the neutral audiovisual. Moreover, the asynchronous-audiovisual induced a greater LPC than the synchronous-audiovisual during the 400–550 ms period. The different integration effects between the fearful and neutral stimuli may reflect the existence of distinct mechanisms of the pre-preparation in terms of the emotional dimension. In light of these results, we present a cross-modal emotional pre-preparation effect involving a three-phase emotional audiovisual integration.
The Impact of Psychopathology, Social Adversity and Stress-relevant DNAm on Prospective Risk for Post-traumatic Stress: A Machine Learning Approach
Authors: Wani Agaz H. , Aiello Allison E. , Kim Grace S. , Xue Fei , Martin Chantel L. , Ratanatharathorn Andrew , Qu Annie , Koenen Karestan , Galea Sandro , Wildman Derek E. , Uddin Monica
Published: September 2020

Background

A range of factors have been identified that contribute to greater incidence, severity, and prolonged course of post-traumatic stress disorder (PTSD), including: comorbid and/or prior psychopathology; social adversity such as low socioeconomic position, perceived discrimination, and isolation; and biological factors such as genomic variation at glucocorticoid receptor regulatory network (GRRN) genes. This complex etiology and clinical course make identification of people at higher risk of PTSD challenging. Here we leverage machine learning (ML) approaches to identify a core set of factors that may together predispose persons to PTSD.

Methods

We used multiple ML approaches to assess the relationship among DNA methylation (DNAm) at GRRN genes, prior psychopathology, social adversity, and prospective risk for PTS severity (PTSS).

Results

ML models predicted prospective risk of PTSS with high accuracy. The Gradient Boost approach was the top-performing model with mean absolute error of 0.135, mean square error of 0.047, root mean square error of 0.217, and R2of 95.29%. Prior PTSS ranked highest in predicting the prospective risk of PTSS, accounting for >88% of the prediction. The top ranked GRRN CpG site was cg05616442, inAKT1, and the top ranked social adversity feature was loneliness.

Conclusion

Multiple factors including prior PTSS, social adversity, and DNAm play a role in predicting prospective risk of PTSS. ML models identified factors accounting for increased PTSS risk with high accuracy, which may help to target risk factors that reduce the likelihood or course of PTSD, potentially pointing to approaches that can lead to early intervention.
TailTimer:an open-source device for automating the rodent tail immersion assay
Authors: Udell Mallory E. , Martinez Angel Garcia , Wang Tengfei , Ni Jie , Hurt Christian , Mulligan Megan , Redei Eva E. , Chen Hao
Published: September 2020

The tail immersion assay is a widely used method for measuring acute thermal pain in a way which is quantifiable and reproducible. It is non-invasive and measures response to a stimulus that may be encountered by an animal in its natural environment. However, tail withdrawal latency data are usually collected manually, and precise temperatures of the water at the time of measurement are most often not recorded. These two factors can reduce the reproducibility of tail immersion assay data. We designed a device,TailTimer, which uses the Raspberry Pi single-board computer and a temperature sensor, to automatically record both tail withdrawal latency and water temperature. The device has a radio frequency identification (RFID) system that can record the ID of animals. Our software recognizes several specific RFID keys as user interface commands, which allowsTailTimerto be operated via RFID fobs. We also programmed the device to only allow tests to be conducted when the water is within ± 0.25 °C of the target temperature. Data recorded using theTailTimerdevice showed a linear relationship between tail withdrawal latency and water temperature when tested between 47 - 50 °C. We also observed a profound effect of water mixing speed on tail withdrawal latency. Our data further revealed significant strain and sex differences, valorizingTailTimerin its ability to detect genetically-determined variations in thermal pain sensitivity.

Significance Statement

Quantification of tail withdrawal latency in response to thermal pain has essentially remained the same since the method was first introduced decades ago and relies on manual recording of water temperature and tail withdrawal latency. Such manual methods engender relatively substantial variability and are potential contributors to some of the discrepancies present among relevant research. The open sourceTailTimerdevice we report here is simple and inexpensive to manufacture. The RFID-based user interface is ergonomic, especially in animal facilities where space is limited and gloves are mandatory. We anticipate that the increased reproducibility of tail withdrawal latency provided byTailTimerwill augment its utility in nociception and addiction research.
Attempted fractionation of LB Lennox medium via reversed phase high performance liquid chromatography
Authors: Ng Wenfa
Published: September 2020

Mass balance analysis is a highly useful tool for chemical engineering analysis of biological processes. Specifically, composition and amounts of inputs to a cell could be correlated with measurement of metabolic byproducts and outputs for inferring metabolic fluxes flowing through specific cellular metabolic pathways. However, the composition of many common microbiological growth medium remains ill-defined with batch-to-batch variation. Thus, a need exists for developing methods for effective fractionation and separation of common growth medium. Using 5 g/L yeast extract, 10 g/L tryptone, and LB Lennox medium as model systems, this work attempted the fractionation of the three complex growth mixtures using C-18 reversed phase high performance liquid chromatography (RP-HPLC). Results revealed no effective fractionation of the three mixtures. More importantly, experiment results indicated that appropriate choice of detection wavelength for visualizing the chromatogram made a huge difference to understanding the effectiveness of fractionation achieved. Specifically, in the case of yeast extract, tryptone and LB Lennox medium, 194 nm may be a more appropriate detection wavelength compared to 280 nm. Collectively, C-18 RP-HPLC was not effective in separating 5 g/L yeast extract, 10 g/L tryptone and LB Lennox medium with hydrophilic mobile phases (ethanol/water mixture).

Graphical abstract

Short description:Visualization of the reversed phase HPLC chromatogram at 194 nm revealed broad peaks and lack of distinct peaks indicative of fractionation of LB Lennox medium by the chromatography method. More importantly, complex ensemble of different components in the growth medium present a significant separation challenge that precludes separation or fractionation by modern liquid chromatography methods. Overall, combinatorial use of both hydrophobic and hydrophilic mobile phase with a C-18 reversed phase column could reveal the presence of a couple of main fractions in a mixture otherwise unable to be separated into distinct components.
Learning at variable attentional load requires cooperation between working memory, meta-learning and attention-augmented reinforcement learning
Authors: Womelsdorf Thilo , Watson Marcus R. , Tiesinga Paul
Published: September 2020

Flexible learning of changing reward contingencies can be realized with different strategies. A fast learning strategy involves using working memory of recently rewarded objects to guide choices. A slower learning strategy uses prediction errors to gradually update value expectations to improve choices. How the fast and slow strategies work together in scenarios with real-world stimulus complexity is not well known. Here, we disentangle their relative contributions in rhesus monkeys while they learned the relevance of object features at variable attentional load. We found that learning behavior across six subjects is consistently best predicted with a model combining (i) fast working memory (ii) slower reinforcement learning from differently weighted positive and negative prediction errors, as well as (iii) selective suppression of non-chosen feature values and (iv) a meta-learning mechanism adjusting exploration rates based on a memory trace of recent errors. These mechanisms cooperate differently at low and high attentional loads. While working memory was essential for efficient learning at lower attentional loads, enhanced weighting of negative prediction errors and meta-learning were essential for efficient learning at higher attentional loads. Together, these findings pinpoint a canonical set of learning mechanisms and demonstrate how they cooperate when subjects flexibly adjust to environments with variable real-world attentional demands.

Significance statement

Learning which visual features are relevant for achieving our goals is challenging in real-world scenarios with multiple distracting features and feature dimensions. It is known that in such scenarios learning benefits significantly from attentional prioritization. Here we show that beyond attention, flexible learning uses a working memory system, a separate learning gain for avoiding negative outcomes, and a meta-learning process that adaptively increases exploration rates whenever errors accumulate. These subcomponent processes of cognitive flexibility depend on distinct learning signals that operate at varying timescales, including the most recent reward outcome (for working memory), memories of recent outcomes (for adjusting exploration), and reward prediction errors (for attention augmented reinforcement learning). These results illustrate the specific mechanisms that cooperate during cognitive flexibility.
Genetic improvement of wheat early vigor promote weed-competitiveness under Mediterranean climate
Authors: Aharon Shlomi , Fadida-Myers Aaviya , Nashef Kamal , Ben-David Roi , Lati Ran N. , Peleg Zvi
Published: September 2020

Chemical weed-control is the most effective practice for wheat, however, rapid evolution of herbicide-resistant weeds threat food-security and calls for integration of non-chemical practices. We hypothesis that integration of GAR dwarfing-genes into elite wheat cultivars can promote early vigor and weed-competitiveness under Mediterranean climate. We develop near-isogenic lines of bread wheat cultivars with GAR dwarfing genes and evaluate them for early vigor and weed-competitiveness under various environmental and management conditions to identify promising NIL for weed-competitiveness and grain yield. While all three NILs, OC1 (Rht8,12), ZC4 (Rht12,13), and BNMF12 (Rht12), responded to gibberellic acid, they exhibited differences in early vigor. Greenhouse and field evaluation highlighted OC1 as a promising line, with significant advantage in early vigor over its parental. To facilitate accurate and continuous early vigor data collection, we applied non-destructive image-based phenotyping approaches which offers non-expensive and end-user friendly solution for selection. NIL OC1 was tested under different weed density level, infestation waves, and temperatures and highlight the complex genotypic × environmental × management interactions. Our findings demonstrate the potential of genetic modification of dwarfing genes as promising approach to improve weed-competitiveness, and serve as basis for future breeding efforts to support sustainable wheat production under semi-arid Mediterranean climate.
Signal separability in integrated neurophotonics
Authors: Yatsenko Dimitri , Moreaux Laurent C. , Choi Jaebin , Tolias Andreas S. , Shepard Kenneth L. , Roukes Michael L.
Published: September 2020

A new modality Photonic probes record fluorescent signals by using arrays of light emitters and detectors embedded in neural tissue. Neither the emitted nor collected light fields are focused. Instead, in proposed configurations, hundreds of emitters will form rapid sequences of structured illumination patterns—providing sufficient spatial and temporal differentiation of neural signals for computational demixing. Here we define criteria for evaluating probe designs for achieving better signal separability. We find that probe geometry has profound, often unintuitive, effects on the separability of neural signals, providing initial design guidelines to achieve separation of individual cells in densely labeled populations.
Defining a Global Map of Functional Group Based 3D Ligand-binding Motifs
Authors: Yang Liu , He Wei , Yun Yuehui , Gao Yongxiang , Zhu Zhongliang , Teng Maikun , Liang Zhi , Niu Liwen
Published: September 2020

Uncovering conserved 3D protein-ligand binding patterns at the basis of functional groups (FGs) shared by a variety of small molecules can greatly expand our knowledge of protein-ligand interactions. Despite that conserved binding patterns for a few commonly used FGs have been reported in the literature, large-scale identification and evaluation of FG-based 3D binding motifs are still lacking. Here, we developed AFTME, an alignment-free method for automatic mapping of 3D motifs to different FGs of a specific ligand through two-dimensional clustering. Applying our method to 233 nature-existing ligands, we defined 481 FG-binding motifs that are highly conserved across different ligand-binding pockets. Systematic analysis further reveals four main classes of binding motifs corresponding to distinct sets of FGs. Combinations of FG-binding motifs facilitate proteins to bind a wide spectrum of ligands with various binding affinities. Finally, we showed that these general binding patterns are also applicable to target-drug interactions, providing new insights into structure-based drug design.
MicroED structure of the human adenosine receptor determined from a single nanocrystal in LCP
Authors: Martynowycz Michael W. , Shiriaeva Anna , Ge Xuanrui , Hattne Johan , Nannenga Brent L. , Cherezov Vadim , Gonen Tamir
Published: September 2020

G Protein-Coupled Receptors (GPCRs), or 7-transmembrane receptors, are a superfamily of membrane proteins that are critically important to physiological processes in the human body. Determining high-resolution structures of GPCRs without signaling partners bound requires crystallization in lipidic cubic phase (LCP). GPCR crystals grown in LCP are often too small for traditional X-ray crystallography. These microcrystals are ideal for investigation by microcrystal electron diffraction (MicroED), but the gel-like nature of LCP makes traditional approaches to MicroED sample preparation insurmountable. Here we show that the structure of a human A2Aadenosine receptor can be determined by MicroED after converting the LCP into the sponge phase followed by cryoFIB milling. We determined the structure of the A2Areceptor to 2.8 Å resolution and resolved an antagonist in its orthosteric ligand-binding site as well as 4 cholesterol molecules bound to the receptor. This study lays the groundwork for future GPCR structural studies using single microcrystals that would otherwise be impossible by other crystallographic methods.

One sentence summary

FIB milled LCP-GPCR structure determined by MicroED
Estimating the Impact of Self-Management Education, Influenza Vaccines, Nebulizers, and Spacers on Healthcare Utilization and Expenditures for Medicaid-Enrolled Children with Asthma
Authors: Yildirim Melike , Griffin Paul , Keskinocak Pinar , O’Connor Jean , Swann Julie L
Published: September 2020

Introduction

We quantify the effect of a set of interventions including asthma self-management education, influenza vaccination, spacers, and nebulizers on healthcare utilization and expenditures for Medicaid-enrolled children with asthma in New York and Michigan.

Methods

We obtained patients’ data from Medicaid Analytic eXtract files and evaluated patients with persistent asthma in 2010 and 2011. We used difference-in-difference regression to quantify the effect of the intervention on the probability of asthma-related healthcare utilization, asthma medication, and utilization costs. We estimated the average change in outcome measures from pre-intervention/intervention (2010) to post-intervention (2011) periods for the intervention group by comparing this with the average change in the control group over the same time horizon.

Results

All of the interventions reduced both utilization and asthma medication costs. Asthma self-management education, nebulizer, and spacer interventions reduced the probability of emergency department (20.8-1.5 %, 95%CI 19.7-21.9% vs. 0.5-2.5% respectively) and inpatient (3.5-0.8%, 95%CI 2.1-4.9% vs. 0.4-1.2%, respectively) utilizations. Influenza vaccine decreased the probability of primary care physician (6-3.5%, 95%CI 4.4-7.6% vs. 1.5-5.5%, respectively) visit. The reductions varied by state and intervention.

Conclusions

Promoting asthma self-management education, influenza vaccinations, nebulizers, and spacers can decrease the frequency of healthcare utilization and asthma-related expenditures while improving medication adherence.
No evidence ofToxoplasma gondiiinfection in urban and rural squirrels
Authors: Kinnunen Riikka P , Schmidt Chloé , Hernández-Ortiz Adrián , Garroway Colin J
Published: September 2020

Wildlife in cities can act as reservoirs for parasites that can infect domestic pets and have implications for human health. For example, the Coccidian parasiteToxoplasma gondiican infect all mammalian species, with felids acting as the only definitive hosts. Rodents, such as squirrels, could play an important role in urban infection dynamics ofT. gondii, as squirrels occur at higher densities in cities than in natural environments and regularly share their territories with cats. In urban and suburban areas squirrels can encounter infectious oocysts shed in cat feces in contaminated soil or in the food they eat. They are also preyed upon by cats making them a potentially important species for completing theT. gondiilife cycle in cities. We hypothesized that due to increased exposure to cats, urban squirrels would be more susceptible toT. gondiiinfection relative to squirrels in more natural areas. We investigated this using molecular and serological methods on samples collected from American red squirrels (Tamiasciurus hudsonicus), eastern grey squirrels (Sciurus carolinensis), northern flying squirrels (Glaucomys sabrinus), and least chipmunks (Tamias minimus) in and around the city of Winnipeg, Manitoba, Canada. We tested a total of 230 tissue samples from 46 squirrels forT. gondiiDNA using quantitative PCR and supplemented these data with analyses of 13 serum samples from grey squirrels (Sciurus carolinensis) testing forT. gondiiantibodies by indirect ELISA. We found no evidence ofT. gondiiinfection in any squirrel. This suggests that squirrels may not be important intermediate hosts ofT. gondiiin cities and do not need to be considered as sources of infection to cats.