bluuebunny/crossref_metadata_2025 huggingface dataset:
Atomic-level evolutionary information improves protein–protein interface scoring
Authors: Quignot Chloé , Granger Pierre , Chacón Pablo , Guerois Raphael , Andreani Jessica
Published: April 2021

Motivation

The crucial role of protein interactions and the difficulty in characterizing them experimentally strongly motivates the development of computational approaches for structural prediction. Even when protein–protein docking samples correct models, current scoring functions struggle to discriminate them from incorrect decoys. The previous incorporation of conservation and coevolution information has shown promise for improving protein–protein scoring. Here, we present a novel strategy to integrate atomic-level evolutionary information into different types of scoring functions to improve their docking discrimination.

Results

We applied this general strategy to our residue-level statistical potential from InterEvScore and to two atomic-level scores, SOAP-PP and Rosetta interface score (ISC). Including evolutionary information from as few as 10 homologous sequences improves the top 10 success rates of individual atomic-level scores SOAP-PP and Rosetta ISC by 6 and 13.5 percentage points, respectively, on a large benchmark of 752 docking cases. The best individual homology-enriched score reaches a top 10 success rate of 34.4%. A consensus approach based on the complementarity between different homology-enriched scores further increases the top 10 success rate to 40%.

Availability and implementation

All data used for benchmarking and scoring results, as well as a Singularity container of the pipeline, are available at http://biodev.cea.fr/interevol/interevdata/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Scalar-on-function local linear regression and beyond
Authors: Ferraty F , NAGY S
Published: April 2021

It is common to want to regress a scalar response on a random function. This paper presents results that advocate local linear regression based on a projection as a nonparametric approach to this problem. Our asymptotic results demonstrate that functional local linear regression outperforms its functional local constant counterpart. Beyond the estimation of the regression operator itself, local linear regression is also a useful tool for predicting the functional derivative of the regression operator, a promising mathematical object in its own right. The local linear estimator of the functional derivative is shown to be consistent. For both the estimator of the regression functional and the estimator of its derivative, theoretical properties are detailed. On simulated datasets we illustrate good finite-sample properties of the proposed methods. On a real data example of a single-functional index model, we indicate how the functional derivative of the regression operator provides an original, fast and widely applicable estimation method.
Phenology, Development, and Parasitism of Allium Leafminer (Diptera: Agromyzidae), a Recent Invasive Species in the United States
Authors: Lingbeek Brandon , Roberts Dana , Elkner Timothy , Gates M , Fleischer Shelby J
Published: April 2021

Allium leafminer, Phytomyza gymnostoma (Diptera: Agromyzidae), is an invasive species first recorded in the Western Hemisphere in 2015 and has expanded its range into northeastern and MidAtlantic states. Its host range encompasses Allium species grown for food and ornamentals, weedy species, species used for pollinator provisioning, and species of conservation concern. Using field and laboratory studies, we advanced methods for rearing, developed a phenology model for spring emergence, describe pupal development, and report on parasitism. Spring emergence was best detected by scouting wild alliums as opposed to emergence cages, and modeled using 350 degree-days above a lower threshold of 1.0°C. Spring adult flight occurred for about 5 wk. Larval development required 22 and 20 d at 17.5 and 25°C, respectively. Pupal development progressed along a color gradient, and an initial presence of fat cell clusters and an air bubble, followed by an exarate pupa. Pupal developed at 3–5% per day at 3°C and reached 25% per day at 21.5°C, but development was not successful at 30°C. Although parasitism rates were low, we documented two Chalcidoidea parasitoids, Halticoptera circulus (Walker) (Hymenoptera: Pteromalidae) and Chrysocharis oscinidis Ashmead (Hymenoptera: Pteromalidae). Together, these data provide baseline information to advance IPM for this invasive species both in crops and noncrop areas.
Three hurdles towards commercialisation: integrating subsistence chickpea producers in the market economy
Authors: Tabe-Ojong Martin Paul Jr , Mausch Kai , Woldeyohanes Tesfaye B , Heckelei Thomas
Published: April 2021

Enhancing agricultural productivity through the adoption of improved technologies presents a credible pathway to economic development and poverty reduction especially through increased commercialisation of production. We used a triple hurdle (TH) model to estimate the production and commercialisation of smallholder farmers in Ethiopia. In doing so, we account for the adoption of improved Cicer arietinum (chickpea) varieties on commercialisation using a three-wave panel data set. We estimate a correlated random effect model with a control function and find the adoption of improved chickpea to have a significant positive effect on smallholder commercialisation. Our findings that are robust over different specifications and identification strategies also support the role of transaction cost in driving market participation (MP). Finally, we argue that the TH model is a better fit to the commonly used double hurdle model for MP, when not all households in a population produce a particular crop.
A new technique for tricuspid valve repair addressing the subvalvular apparatus in functional tricuspid regurgitation
Authors: Doenst Torsten , Faerber Gloria
Published: April 2021

Annular dilatation is the main mechanism for tricuspid regurgitation, but right ventricular dilatation often adds a restrictive mechanism, which may limit durability. We describe a subvalvular technique anchoring the chordal origins to the annuloplasty, with the aim to stabilize valve geometry and increase durability. A Goretex suture is attached to the anterior papillary muscle. One arm of the suture is stitched through the septal muscle and both arms are atrialized underneath the septal leaflet and tied to the annuloplasty band. In 12 patients (75 ± 6 years, EuroSCORE II 10 ± 9%), severe-torrential tricuspid regurgitation was successfully reduced to mild. Results were stable in all but one patient during follow-up (1–15 months). NYHA class and general health status was improved. This subvalvular technique is safe with the potential to generate a durable repair.
The notion of almost zeros and randomness
Authors: Leventides J , Karcanias N , Poulios N C
Published: April 2021

We investigate the problem of almost zeros of polynomial matrices as used in system theory. It is related to the controllability and observability notion of systems as well as the determination of Macmillan degree and complexity of systems. We also present some new results on this important invariant in the light of randomness and we prove an uncertainty type relation appearing in such ensembles of operators.
Comparative macrolide use in humans and animals: should macrolides be moved off the World Health Organisation’s critically important antimicrobial list?
Authors: Trott Darren J , Turnidge John , Kovac Jessica H , Simjee Shabbir , Wilson Danny , Watts Jeffrey
Published: April 2021

Macrolide antibiotics are categorized by the WHO as Highest Priority, Critically Important Antimicrobials due to their recommendation as treatment for severe cases of campylobacteriosis in humans; a self-limiting, rarely life-threatening, zoonotic foodborne infection. Low rates of macrolide resistance in Campylobacter jejuni and the availability of alternative treatments have prompted some regulatory schemes to assign macrolides to a lower importance category. Apart from rare, specific infections, macrolides largely play a supportive role to other drug classes in human medicine. By contrast, although the advent of alternative control methods has seen significant reductions in macrolide use in intensive livestock, they still have a crucial role in the treatment/control of respiratory infections and liver abscesses in cattle. Whilst acknowledging that ongoing surveillance is required to reduce the spread of recently emerged, transferable macrolide resistance among Campylobacter, this article recommends that macrolides should be moved to the WHO Highly Important category.
Emotional Support from AI Chatbots: Should a Supportive Partner Self-Disclose or Not?
Authors: Meng Jingbo , Dai Yue (Nancy)
Published: April 2021

This study examined how and when a chatbot’s emotional support was effective in reducing people’s stress and worry. It compared emotional support from chatbot versus human partners in terms of its process and conditional effects on stress/worry reduction. In an online experiment, participants discussed a personal stressor with a chatbot or a human partner who provided none, or either one or both of emotional support and reciprocal self-disclosure. The results showed that emotional support from a conversational partner was mediated through perceived supportiveness of the partner to reduce stress and worry among participants, and the link from emotional support to perceived supportiveness was stronger for a human than for a chatbot. A conversational partner’s reciprocal self-disclosure enhanced the positive effect of emotional support on worry reduction. However, when emotional support was absent, a solely self-disclosing chatbot reduced even less stress than a chatbot not providing any response to participants’ stress.

Lay Summary

In recent years, AI chatbots have increasingly been used to provide empathy and support to people who are experiencing stressful times. This study compared emotional support from a chatbot compared to that of a human who provided support. We were interested in examining which approach could best effectively reduce people’s worry and stress. When either a person or a chatbot was able to engage with a stressed individual and tell that individual about their own experiences, they were able to build rapport. We found that this type of reciprocal self-disclosure was effective in calming the worry of the individual. Interestingly, if a chatbot only reciprocally self-disclosed but offered no emotional support, the outcome was worse than if the chatbot did not respond to people at all. This work will help in the development of supportive chatbots by providing insights into when and what they should self-disclose.
Post-pancreatic necrosectomy biliary fistula: thinking beyond the box
Authors: Pandit Narendra , Awale Laligen , Deo Kunal Bikram , Pradhan Bickram
Published: April 2021

Walled-off pancreatic necrosis is a challenging problem and pancreatic necrosectomy is associated with significant morbidity and mortality. Following necrosectomy, postoperative bile leak is a rare complication. We present such a case of delayed bile leak from the distal common bile duct in an 81-year-old lady following pancreatic necrosectomy, which was successfully managed by endoscopic stenting.
Hospital Presentation for Self-Harm in Youth as a Risk Marker for Later Psychotic and Bipolar Disorders: A Cohort Study of 59 476 Finns
Authors: Bolhuis Koen , Lång Ulla , Gyllenberg David , Kääriälä Antti , Veijola Juha , Gissler Mika , Kelleher Ian
Published: April 2021

Expanding clinical strategies to identify high risk groups for psychotic and bipolar disorders is a research priority. Considering that individuals diagnosed with psychotic and bipolar disorder are at high risk of self-harm, we hypothesised the reverse order relationship would also be true (ie, self-harm would predict psychotic/bipolar disorder). Specifically, we hypothesised that hospital presentation for self-harm would be a marker of high risk for subsequent development of psychotic/bipolar disorder and sought to test this hypothesis in a large population sample. This prospective register-based study included everyone born in Finland in 1987, followed until age 28 years (N = 59 476). We identified all hospital records of self-harm presentations, as well as all ICD-10 healthcare registrations of first diagnoses of psychotic and bipolar disorders. Cox proportional hazards models were used to assess the relationship between self-harm and psychotic/bipolar disorders. Of all individuals who presented to hospital with self-harm (n = 481), 12.8% went on to receive a diagnosis of psychosis (hazard ratio [HR] = 6.03, 95% confidence interval [CI] 4.56–7.98) and 9.4% a diagnosis of bipolar disorder (HR = 7.85, 95% CI 5.73–10.76) by age 28 years. Younger age of first self-harm presentation was associated with higher risk—for individuals who presented before age 18 years, 29.1% developed a psychotic or bipolar disorder by age 28 years. Young people who present to hospital with self-harm are at high risk of future psychotic and bipolar disorders. They represent an important cohort for the prevention of serious mental illness.
Weight change and resolution of fatty liver in normal weight individuals with nonalcoholic fatty liver disease
Authors: Sinn Dong Hyun , Kang Danbee , Cho Soo Jin , Paik Seung Woon , Guallar Eliseo , Cho Juhee , Gwak Geum-Youn
Published: April 2021

Objectives

Obesity is a well-known risk factor for nonalcoholic fatty liver disease (NAFLD), and weight reduction is primarily recommended for managing the disease. However, some NAFLD patients have a normal weight (lean NAFLD), and whether weight reduction is also recommendable for lean NAFLD patients remains unclear.

Methods

We conducted a longitudinal study of 16 738 adults (average age, 50.5 years; lean NAFLD, 2383 participants) with NAFLD at baseline who underwent repeated health check-up examinations, including bodyweight measurements and abdominal ultrasonography from January 2003 through December 2013.

Results

During 68 389 person-years of follow-up (median follow-up of 3.00 years), 5819 patients had a fatty liver resolution. Compared with participants who had no weight reduction or increased weight, the fully adjusted hazard ratios for fatty liver resolution in participants with 0–4.9, 5–9.9 and 10% or more weight reduction were 1.67 [95% confidence interval (CI), 1.57–1.77], 3.36 (95% CI, 3.09–3.65) and 5.50 (95% CI, 4.83–6.27), respectively. The association between weight reduction and the fatty liver resolution was stronger in overweight/obese NAFLD participants but was also evident in lean NAFLD participants in a dose-dependent manner. In spline regression models, the association between weight change and the fatty liver resolution was linear among participants with normal weight.

Conclusion

There was a dose-dependent association between weight reduction and fatty liver resolution in both lean and overweight/obese NAFLD patients. This finding suggests weight reduction as a primary recommendation for lean NAFLD patients as in overweight/obese NAFLD patients.
Applying a machine learning modelling framework to predict delayed linkage to care in patients newly diagnosed with HIV in Mecklenburg County, North Carolina, USA
Authors: Chen Shi , Owolabi Yakubu , Dulin Michael , Robinson Patrick , Witt Brian , Samoff Erika
Published: April 2021

Background:

Machine learning has the potential to help researchers better understand and close the gap in HIV care delivery in large metropolitan regions such as Mecklenburg County, North Carolina, USA.

Objectives:

We aim to identify important risk factors associated with delayed linkage to care for HIV patients with novel machine learning models and identify high-risk regions of the delay.

Methods:

Deidentified 2013–2017 Mecklenburg County surveillance data in eHARS format were requested. Both univariate analyses and machine learning random forest model (developed in R 3.5.0) were applied to quantify associations between delayed linkage to care (>30 days after diagnosis) and various risk factors for individual HIV patients. We also aggregated linkage to care by zip codes to identify high-risk communities within the county.

Results:

Types of HIV-diagnosing facility significantly influenced time to linkage; first diagnosis in hospital was associated with the shortest time to linkage. HIV patients with lower CD4+ cell counts (<200/ml) were twice as likely to link to care within 30 days than those with higher CD4+ cell count. Random forest model achieved high accuracy (>80% without CD4+ cell count data and >95% with CD4+ cell count data) to predict risk of delay in linkage to care. In addition, we also identified top high-risk zip codes of delayed linkage.

Conclusion:

The findings helped public health teams identify high-risk communities of delayed HIV care continuum across Mecklenburg County. The methodology framework can be applied to other regions with HIV epidemic and challenge of delayed linkage to care.
COVID transmission and contact tracing using WHO risk assement tool among frontline healthcare workers : Insights from a South Indian tertiary care centre
Authors: Moni Merlin , Kulirankal Kiran G , Prasanna Preetha , Mary Ann , Thomas Elizabeth Mary , Sundaram Rejitha P , Babu Binil , Bindu Veena , Edathadathil Fabia , Madathil Sai Bala , Beena K V , Sathyapalan Dipu T
Published: April 2021

Background

The high exposure risk to COVID among frontline heathcare workers was a major challenge to healthcare systems across the globe that warranted close monitoring through risk assessment and contact tracing strategies. The objective of our study was to characterize exposure risk factors for transmission and subsequent COVID positivity among the frontlinehealthcare workers in our institution during the pandemic period.

Methods

The retrospective observational study conducted over a period of 6 months from June 2020 to November 2020 at a 1300-bedded South Indian tertiary care centre included frontline healthcare workers who were assessed for their identified encounter with COVID positive individual using a modified WHO COVID risk assessment tool. Additional risk attributes of exposure characterized among COVID positive healthcare workers comprised of shared space, cluster related transmissions and multiple instances of exposure to COVID.

Results

Among a total of 4744 contacts with COVID positive individuals assessed for risk stratification during the study period, 942 (19.8%) were high risk and 3802 (80.2%) were low risk exposures respectively. 106 (2.2%) turned COVID positive during the surveillance period of 14 days. Frontline workers working in COVID areas had significant low COVID rates as compared to other areas (N=1, 0.9%). The average monthly COVID positivity rates being 1.66%, the attack rates among high risk and low risk contacts among the total HCWs screened were 5% (46/942) and 1.57% (60/3802) respectively. Shared space (70%) and IPC breaches (66%) were found to be highly prevalent in the COVID positive cohort, along with maskless encounters (43%) and multiple exposure (39%). The attack rate among the 6 identified COVID cluster groups (5.5%) were found to be higher than the attack rate (2.2%) noted among the total contacts screened and no significant association was observed between risk categories in the clusters.

Discussion

Our study highlights higher risk of COVID positivity among high risk contacts as compared to low risk contacts. However, the high COVID positivity rate in low risk group among cluster transmissions and its lack of association with risk assessment highlight the suboptimal utility of the risk assessment strategy among cluster groups.
Violence and Non-fatal Injuries among Vietnamese In-school Adolescents: National Prevalence Estimates and Associated Factors
Authors: Le Phuong Anh , Hoang Van Minh , Tran Thi Tuyet Hanh , Khuong Quynh Long , Takeuchi Momoe , Nguyen Tuan Lam , Pham Thi Quynh Nga , Le Van Tuan , Tran Quoc Bao , Park Kidong
Published: April 2021

Background

School violence and injury are major public health problems worldwide; however, current information on these issues in Vietnam is lacking. We aim to investigate the prevalence of violence and non-fatal injury and associated factors among Vietnamese adolescents aged 13-17 years old.

Methods

We used data from the 2019 Vietnam Global School-based Student Health Survey (GSHS), which is a nationally representative survey developed by the World Health Organization to monitor behavioral risk factors among school-aged students. The Vietnam GSHS 2019 was conducted in 20 provinces and cities, with a sample size of 7,690 male and female students aged 13-17 years old.

Results

We found the prevalence of violence and non-fatal injury was 14.5% and 21.4%, respectively. Common risk factors for both violence and non-fatal injuries included cigarette smoking, alcohol use, mental health problems, and living with neither parent; violence was also a risk factor for non-fatal injuries. Student older age was associated with lower odds of school violence. Parents played an important role in preventing violence among female students and non-fatal injuries in both genders.

Conclusions

Future policies should consider individual factors as well as adolescent-parent bonding, to mitigate the burden of violence and injury among in-school adolescents in Vietnam.
The impact of technology systems and professional support in digital mental health interventions: a secondary meta-analysis
Authors: Sasseville Maxime , LeBlanc Annie , Tchuente Jack , Boucher Mylène , Dugas Michèle , Gisèle Mbemba , Barony Romina , Chouinard Maud-Christine , Beaulieu Marianne , Beaudet Nicolas , Skidmore Becky , Cholette Pascale , Aspiros Christine , Larouche Alain , Chabot Guylaine , Gagnon Marie-Pierre
Published: April 2021

Background

A rapid review of systematic reviews was conducted to assess the effectiveness of digital mental health interventions for people with a chronic disease. Although it provided an overview of the evidence, it offered limited understanding of ethe types of interventions that were the most effective. The aim of this study was to perform a meta-analysis of primary studies identified in this rapid review of systematic reviews by focusing on the needs of knowledge users.

Methods

This secondary meta-analysis follows a rapid review of systematic reviews, a virtual workshop with knowledge users to identify research questions and a modified Delphi study to guide research methods. We conducted a secondary analysis of the primary studies identified in the rapid review. Two reviewers independently screened the titles and abstracts and applied inclusion criteria: RCT design using a digital mental health intervention in a population of adults with another chronic condition, published after 2010 in French or English, and including an outcome measurement of anxiety or depression.

Results

708 primary studies were extracted from the systematic reviews and 84 primary studies met the inclusion criteria Digital mental health interventions were significantly more effective than in-person care for both anxiety and depression outcomes. Online messaging was the most effective technology to improve anxiety and depression scores; however, all technology types were effective. Interventions partially supported by healthcare professionals were more effective than self-administered.

Conclusions

While our meta-analysis identifies digital intervention’s characteristics that are more effective, all technologies and levels of support can be used considering implementation context and population.

Review registration

The protocol for this review is registered in the National Collaborating Centre for Methods and Tools (NCCMT) COVID-19 Rapid Evidence Service (ID 75).
Molecular analysis suggests oligoclonality and metastasis of endometriosis lesions across anatomically defined subtypes
Authors: Praetorius Teresa H. , Leonova Anna , Lac Vivian , Senz Janine , Tessier-Cloutier Basile , Nazeran Tayyebeh M. , Köbel Martin , Grube Marcel , Kraemer Bernhard , Yong Paul J. , Kommoss Stefan , Anglesio Michael S.
Published: April 2021

Endometriosis symptoms are heterogeneous with controversy on whether it constitutes a single disease or multiple distinct types. Our previous work found recurrent somatic cancer-driver alterations in endometriosis; however, these have not been found ubiquitously. A handful of cases spread across studies also suggest mutations might be shared (clonal) between lesions of the same type. As current classification systems correlate poorly with symptoms or outcomes, somatic genomics may improve the current system. Here, we investigate heterogeneity of somatic cancer-driver mutations within patients and across endometriosis types. We examined anatomically distinct types of endometriosis (ovarian, deep infiltrating, and superficial endometriosis) in 27 individual patients all of whom had at least two types of endometriosis. Specimens were analyzed using high-sensitivity targeted sequencing with orthogonal validation from droplet digital PCR and mutation-surrogate immunohistochemistry. Results found 13/27 patients had informative somatic driver mutation in endometriosis, 9/13 had identical mutations across distinct lesions. Endometriomas tended to have a higher mutational complexity, with functionally redundant driver mutations in same gene and within the same lesions.

Our data are consistent with clonality across endometriosis lesions regardless of subtype. Further the finding of redundancy in mutations with the same gene and lesions is also consistent with endometriosis representing an oligoclonal disease with dissemination likely to consist of multiple epithelial clones travelling together. This suggests the current anatomically defined classification of endometriosis does not fully recognize the etiology of the disease. A novel classification should take into account genomic and other molecular features. These findings could further contribute to development of a more personalized endometriosis diagnosis and care.
The impact of population mobility on COVID-19 incidence and socioeconomic disparities at the sub-city level in 314 Latin American cities
Authors: Kephart Josiah L. , Delclòs-Alió Xavier , Bilal Usama , Sarmiento Olga L. , Barrientos-Gutiérrez Tonatiuh , Ramirez-Zea Manuel , Quistberg D. Alex , Rodríguez Daniel A. , Roux Ana V. Diez
Published: April 2021

Background

Little is known about the impact of changes in mobility at the sub-city level on subsequent COVID-19 incidence or the contribution of mobility to socioeconomic disparities in COVID-19 incidence.

Methods

We compiled aggregated mobile phone location data, COVID-19 confirmed cases, and features of the urban and social environments to analyze linkages between population mobility, COVID-19 incidence, and educational attainment at the sub-city level among cities with >100,000 inhabitants in Argentina, Brazil, Colombia, Guatemala, and Mexico from March to August 2020. We used mixed effects negative binomial regression to examine longitudinal associations between changes in weekly mobility (lags 1-6 weeks) and subsequent COVID-19 incidence at the sub-city level, adjusting for urban environmental factors.

Findings

Among 1,031 sub-cities representing 314 cities in five Latin American countries, 10% higher weekly mobility was associated with 8.5% (95% CI 7.4% to 9.5%) higher weekly COVID-19 incidence the following week. This association gradually declined as the lag between mobility and COVID-19 incidence increased and was not different from the null at a six-week lag. We found evidence that suggests differences in mobility reductions are a driver of socioeconomic disparities in COVID-19 incidence.

Interpretation

Lower population movement within a sub-city is associated with lower risk of subsequent COVID-19 incidence among residents of that sub-city. Implementing policies that reduce population mobility at the sub-city level may be an impactful COVID-19 mitigation strategy that takes equity into consideration and reduces economic and social disruption at the city or regional level.

Funding

Wellcome Trust
Adverse effects of COVID-19 vaccination: machine learning and statistical approach to identify and classify incidences of morbidity and post-vaccination reactogenicity
Authors: Ahamad Md. Martuza , Aktar Sakifa , Uddin Md. Jamal , Rashed-Al-Mahfuz Md. , Azad AKM , Uddin Shahadat , Alyami Salem A. , Sarker Iqbal H. , Liò Pietro , Quinn Julian M.W. , Moni Mohammad Ali
Published: April 2021

Good vaccine safety and reliability are essential to prevent infectious disease spread. A small but significant number of apparent adverse reactions to the new COVID-19 vaccines have been reported. Here, we aim to identify possible common causes for such adverse reactions with a view to enabling strategies that reduce patient risk by using patient data to classify and characterise patients those at risk of such reactions. We examined patient medical histories and data documenting post-vaccination effects and outcomes. The data analyses were conducted by different statistical approaches followed by a set of machine learning classification algorithms. In most cases, similar features were significantly associated with poor patient reactions. These included patient prior illnesses, admission to hospitals and SARS-CoV-2 reinfection. The analyses indicated that patient age, gender, allergic history, taking other medications, type-2 diabetes, hypertension and heart disease are the most significant pre-existing factors associated with risk of poor outcome and long duration of hospital treatments, pyrexia, headache, dyspnoea, chills, fatigue, various kind of pain and dizziness are the most significant clinical predictors. The machine learning classifiers using medical history were also able to predict patients most likely to have complication-free vaccination with an accuracy score above 85%. Our study identifies profiles of individuals that may need extra monitoring and care (e.g., vaccination at a location with access to comprehensive clinical support) to reduce negative outcomes through classification approaches. Important classifiers achieving these reactions notably included allergic susceptibility and incidence of heart disease or type-2 diabetes.
A machine learning based aging measure among middle-aged and older Chinese adults: the China Health and Retirement Longitudinal Study
Authors: Cao Xinqi , Yang Guanglai , Jin Xurui , He Liu , Li Xueqin , Zheng Zhoutao , Liu Zuyun , Wu Chenkai
Published: April 2021

Background

Biological age (BA) has been accepted as a more accurate proxy of aging than chronological age (CA). This study aimed to use machine learning (ML) algorithms to estimate BA in the Chinese population.

Methods

We used data from 9,771 middle-aged and older (≥ 45 years) Chinese adults in the China Health and Retirement Longitudinal Study. We used several ML algorithms (e.g., Gradient Boosting Regressor, Random Forest, CatBoost Regressor, and Support Vector Machine) to develop new measures of biological aging (ML-BAs) based on physiological biomarkers. R-squared value and mean absolute error (MAE) were used to determine the optimal performance of these ML-BAs. We used logistic regression models to examine the associations of the best ML-BA and a conventional aging measure – Klemera and Doubal method-biological age (KDM-BA) we previously developed – with physical disability and mortality, respectively.

Results

The Gradient Boosting Regression model performed best, resulting in a ML-BA with R-squared value of 0.270 and MAE of 6.519. This ML-BA was significantly associated with disability in basic activities of daily living, instrumental activities of daily living, lower extremity mobility, and upper extremity mobility, and mortality, with odds ratios ranging from 1% to 7% (per one-year increment in ML-BA, all P <0.001), independent of CA. These associations were generally comparable to that of KDM-BA.

Conclusion

This study provides a valid ML-based measure of biological aging for middle-aged and older Chinese adults. These findings support the application of ML in geroscience research and help facilitate the understanding of the aging process.
DIETARY RESCUE OF ADULT BEHAVIORAL DEFICITS IN THEFMR1KNOCKOUT MOUSE
Authors: Nolan Suzanne O. , Hodges Samantha L. , Binder Matthew S. , Smith Gregory D. , Okoh James T. , Jefferson Taylor S. , Escobar Brianna , Lugo Joaquin N.
Published: April 2021

The current study aimed to further address important questions regarding the therapeutic efficacy of omega-3 fatty acids for various behavioral and neuroimmune aspects of theFmr1phenotype. To address these questions, our experimental design utilized two different omega-3 fatty acid administration timepoints, compared to both standard laboratory chow controls (“Standard”) and a diet controlling for the increase in fat content (“Control Fat”). In the first paradigm, post-weaning supplementation (after postnatal day 21) with the omega-3 fatty acid diet (“Omega-3”) reversed deficits in startle threshold, but not deficits in prepulse inhibition, and the effect on startle threshold was not specific to the Omega-3 diet. However, post-weaning supplementation with both experimental diets also impaired acquisition of a fear response, recall of the fear memory and contextual fear conditioning compared to the Standard diet. The post-weaning Omega-3 diet reduced hippocampal expression of IL-6 and this reduction of IL-6 was significantly associated with diminished performance in the fear conditioning task. In the prenatal experimental paradigm, the Omega-3 diet attenuated hyperactivity and acquisition of a fear response. Additionally, prenatal exposure to the Control Fat diet (similar to a “Western” diet) further diminished nonsocial anxiety in theFmr1knockout. This study provides significant evidence that dietary fatty acids throughout the lifespan can significantly impact the behavioral and neuroimmune phenotype of theFmr1knockout model.
Feasibility and diagnostic accuracy of saliva-based SARS-CoV-2 screening in educational settings and children aged < 12 years
Authors: Hoch Martin , Vogel Sebastian , Eberle Ute , Kolberg Laura , Gruenthaler Valerie , Fingerle Volker , Ackermann Nikolaus , Sing Andreas , Liebl Bernhard , Huebner Johannes , Kuttiadan Simone , Rack-Hoch Anita , Meyer-Buehn Melanie , Schober Tilmann , Both Ulrich von
Published: April 2021

Children have been disproportionately affected during the COVID-19 pandemic. We aimed to assess a saliva-based algorithm for SARS-CoV-2 testing to be used in schools and childcare institutions under pandemic conditions. A weekly SARS-CoV-2 sentinel study in primary schools, kindergartens and childcare facilities was conducted over a 12-week-period. In a sub-study covering 7 weeks, 1895 paired oropharyngeal and saliva samples were processed for SARS-CoV-2 rRT-PCR testing in both asymptomatic children (n=1243) and staff (n=652). Forty-nine additional concurrent swab and saliva samples were collected from SARS-CoV-2 infected patients (patient cohort). The Salivette® system was used for saliva collection and assessed for feasibility and diagnostic performance. For children a mean of 1.18 ml saliva could be obtained. Based on results from both cohorts, the Salivette® testing algorithm demonstrated specificity of 100% (95% CI 99.7 - 100) and sensitivity of 94.9% (95% CI 81.4 - 99.1) with oropharyngeal swabs as reference. Agreement between sampling systems was 100% for moderate to high viral load situations (defined as Ct-values < 33 from oropharyngeal swabs). Comparative analysis of Ct-values derived from saliva vs. oropharyngeal swabs demonstrated a significant difference (mean 4.23; 95% CI 2.48–6.00). In conclusion, the Salivette® system proved to be an easy-to-use, safe and feasible saliva collection method and a more pleasant alternative to oropharyngeal swabs for SARS-CoV-2 testing in children aged 3 years and above.
Identification of unknown proteins in X-ray crystallography and cryo-EM
Authors: Chojnowski Grzegorz , Simpkin Adam J. , Leonardo Diego A. , Seifert-Davila Wolfram , Vivas-Ruiz Dan E. , Keegan Ronan M. , Rigden Daniel J.
Published: April 2021

Although experimental protein structure determination usually targets known proteins, chains of unknown sequence are often encountered. They can be purified from natural sources, appear as an unexpected fragment of a well characterized protein or as a contaminant. Regardless of the source of the problem, the unknown protein always requires tedious characterization. Here we present an automated pipeline for the identification of protein sequences from cryo-EM reconstructions and crystallographic data. We present the method’s application to characterize the crystal structure of an unknown protein purified from a snake venom. We also show that the approach can be successfully applied to the identification of protein sequences and validation of sequence assignments in cryo-EM protein structures.
Rapid decay of host basal mRNAs during SARS-CoV-2 infection perturbs host antiviral mRNA biogenesis and export
Authors: Burke James M. , St Clair Laura A. , Perera Rushika , Parker Roy
Published: April 2021

A key feature of the mammalian innate immune response to viral infection is the transcriptional induction of interferon (IFN) genes, which encode for secreted proteins that prime the antiviral response and limit viral replication and dissemination. A hallmark of severe COVID-19 disease caused by SARS-CoV-2 is the low presence of IFN proteins in patient serum despite elevated levels ofIFN-encoding mRNAs, indicative of post-transcriptional inhibition of IFN protein production. Herein, we show SARS-CoV-2 infection limits type I and type III IFN biogenesis by preventing the release of mRNA from their sites of transcription and/or triggering their nuclear degradation. In addition, SARS-CoV-2 infection inhibits nuclear-cytoplasmic transport ofIFNmRNAs as a consequence of widespread cytosolic mRNA degradation mediated by both activation of the host antiviral endoribonuclease, RNase L, and by the SARS-CoV-2 protein, Nsp1. These findings argue that inhibition of host and/or viral Nsp1-mediated mRNA decay, as well as IFN treatments, may reduce viral-associated pathogenesis by promoting the innate immune response.
Organic management and landscape heterogeneity combine to sustain multifunctional bird communities in European vineyards
Authors: Barbaro Luc , Assandri Giacomo , Brambilla Mattia , Castagneyrol Bastien , Froidevaux Jérémy , Giffard Brice , Pithon Joséphine , Puig‐Montserrat Xavier , Torre Ignasi , Calatayud François , Gaüzère Pierre , Guenser Josépha , Macià‐Valverde Francesc‐Xavier , Mary Séverine , Raison Laurent , Sirami Clélia , Rusch Adrien
Published: April 2021

Conserving functionally diverse bird communities in European farmland is becoming critical, with no exception for regions of wine production. Management intensification combined with the loss of semi‐natural habitats in wine‐growing landscapes has led to a long‐term decline not only in birds of conservation concern but also in once common insectivores and seed eaters. These declines are expected not only to threaten key ecological services provided by vineyard birds, such as pest or weed control, but also their cultural significance.

We analysed how organic management and landscape heterogeneity affected taxonomic and functional diversity of 334 bird communities from 12 regions of the three main wine‐producing European countries (France, Italy and Spain). We further modelled the responses of community‐level metrics measuring mean habitat specialization and bird song attractiveness to humans, as well as cumulative abundances of functional insectivores, seed and grape eaters to account for individual avian functions.

We found that organic viticulture enhanced bird functional diversity and individual functions, but that its positive effect partially depended on grass cover management in the inter‐rows and landscape heterogeneity. Woodland cover and landscape compositional heterogeneity increased both taxonomic and functional diversity of bird communities, as well as functional insectivory. Landscape configurational heterogeneity also increased functional diversity and mean song attractiveness of bird communities.

Overall, both bird diversity and functions were enhanced by higher landscape heterogeneity, especially in organic vineyards. However, mean habitat specialization decreased with woodland cover and configurational heterogeneity, meaning that open habitat specialists preferred more even landscapes with high vineyard cover.

Synthesis and applications. Our study highlights the benefits of combining organic management and partial grass cover at the field level and promoting interfaces between vineyards and semi‐natural habitats at the landscape level to sustain multifunctional bird communities in wine‐producing European countries.
Long‐term surveys support declines in early season forest plants used by bumblebees
Authors: Mola John M. , Richardson Leif L. , Spyreas Greg , Zaya David N. , Pearse Ian S.
Published: April 2021

Populations of bumblebees and other pollinators have declined over the past several decades due to numerous threats, including habitat loss and degradation. However, we can rarely investigate the role of resource loss due to a lack of detailed long‐term records of forage plants and habitats.

We used 22‐year repeated surveys of more than 262 sites located in grassland, forest, and wetland habitats across Illinois, USA to explore how the abundance and richness of bumblebee food plants have changed over the period of decline of the endangered rusty patched bumblebee Bombus affinis.

We documented a decline in abundance of bumblebee forage plants in forest understories, which our phenology analysis suggests provide the primary nectar and pollen sources for foundress queens in spring, a critical life stage in bumblebee demography. By contrast, the per‐unit area abundance of food plants in primarily midsummer‐flowering grassland and wetland habitats had not declined. However, the total area of grasslands had declined across the region resulting in a net loss of grassland resources.

Synthesis and applications. Our results suggest a decline in spring‐flowering forest understorey plants is a previously unappreciated bumblebee stressor, compounding factors like agricultural intensification, novel pathogen exposure and grassland habitat loss. These findings emphasize the need for greater consideration of habitat complementarity in bumblebee conservation. We conclude that the continued loss of early season floral resources may add additional stress to critical life stages of bumblebees and limit restoration efforts if not explicitly considered in pollinator conservation.
Extracellular sulfite is protective against reactive oxygen species and antibiotic stress in Shewanella oneidensis MR‐1
Authors: Goff Jennifer L. , Schaefer Jeffra K. , Yee Nathan
Published: April 2021

In this study, we investigated the extracellular reactive sulfur species produced by Shewanella oneidensis MR‐1 during growth. The results showed that sulfite is the major extracellular sulfur metabolite released to the growth medium under both aerobic and anaerobic growth conditions. Exogenous sulfite at physiological concentrations protected S. oneidensis MR‐1 from hydrogen peroxide toxicity and enhanced tolerance to the beta‐lactam antibiotics cefazolin, meropenem, doripenem and ertapenem. These findings suggest that the release of extracellular sulfite is a bacterial defence mechanism that plays a role in the mitigation of environmental stress.
Meeting unique requirements: Community consultation and public disclosure for research in emergency setting using exception from informed consent
Authors: Dickert Neal W. , Metz Kathleen , Fetters Michael D. , Haggins Adrianne N. , Harney Deneil K. , Speight Candace D. , Silbergleit Robert
Published: April 2021

Background

Exception from informed consent (EFIC) regulations for research in emergency settings contain unique requirements for community consultation and public disclosure. These requirements address ethical challenges intrinsic to this research context. Multiple approaches have evolved to accomplish these activities that may reflect and advance different aims. This scoping review was designed to identify areas of consensus and lingering uncertainty in the literature.

Methods

Scoping review methodology was used. Conceptual and empirical literature related to community consultation and public disclosure for EFIC research was included and identified through a structured search using Embase, HEIN Online, PubMed, and Web of Science. Data were extracted using a standardized tool with domains for major literature categories.

Results

Among 84 manuscripts, major domains included conceptual or policy issues, reports of community consultation processes and results, and reports of public disclosure processes and results. Areas of consensus related to community consultation included the need for a two‐way exchange of information and use of multiple methods. Public acceptance of personal EFIC enrollment is commonly 64% to 85%. There is less consensus regarding how to assess attitudes, what “communities” to prioritize, and how to determine adequacy for individual projects. Core goals of public disclosure are less well developed; no metrics exist for assessing adequacy.

Conclusions

Multiple methods are used to meet community consultation and public disclosure requirements. There remain no settled norms for assessing adequacy of public disclosure, and there is lingering debate about needed breadth and depth of community consultation.
Quantifying direct and indirect effect for longitudinal mediator and survival outcome using joint modeling approach
Authors: Zheng Cheng , Liu Lei
Published: April 2021

Longitudinal biomarkers are widely used in biomedical and translational researches to monitor the progressions of diseases. Methods have been proposed to jointly model longitudinal data and survival data, but its causal mechanism is yet to be investigated rigorously. Understanding how much of the total treatment effect is through the biomarker is important in understanding the treatment mechanism and evaluating the biomarker. In this work, we propose a causal mediation analysis method to compute the direct and indirect effects, when a joint modeling approach is used to take the longitudinal biomarker as the mediator and the survival endpoint as the outcome. Such a joint modeling approach allows us to relax the commonly used “sequential ignorability” assumption. We demonstrate how to evaluate longitudinally measured biomarkers using our method with two case studies, an AIDS study and a liver cirrhosis study.
ENT from afar: Opportunities for remote patient assessment, clinical management, teaching and learning
Authors: Bhutta Mahmood F. , Swanepoel De Wet , Fagan Johan
Published: April 2021

Remote communication in ENT has been expanding, spurred by the COVID‐19 pandemic. Conferences and teaching have moved online, enabling easier participation and reducing financial and environmental costs. Online multi‐disciplinary meetings have recently been instigated in Africa to discuss management of cases in head and neck cancer, or cochlear implantation, expanding access and enhancing patient care. Remote patient consultation has also seen an explosion, but existing literature suggests some caution, particularly because many patients in ENT need an examination to enable definitive diagnosis. Ongoing experience will help us to better understand how remote communication will fit into our future working lives, and also where face‐to‐face interaction may still be preferable.