bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Biological Agents in the Treatment of SARS-CoV-2–Associated Multisystem Inflammatory Syndrome in Children
Authors: Çelikel Elif , Tekin Zahide Ekici , Aydin Fatma , Emeksiz Serhat , Uyar Emel , Özcan Serhan , Perk Oktay , Sezer Müge , Tekgöz Nilüfer , Coşkun Serkan , Güngörer Vildan , Gül Ayşe Esin Kibar , Bayhan Gülsüm İclal , Özbek Namik , Azili Müjdem Nur , Acar Banu Çelikel
Published: April 2021

Objectives

The aims of this study were to evaluate the role of biological agents in the treatment of severe multisystem inflammatory syndrome in children (MIS-C) and to assess the current application, outcomes, and adverse effects in patients who are followed up in a pediatric intensive care unit (PICU).

Patients and Methods

This observational, descriptive, medical records review study was performed on patients with MIS-C admitted to the PICU between September 1 and November 1, 2020. Through medical records review, we confirmed that patients were positive for current or recent SARS-CoV-2 infection or for COVID-19 exposure history within the 4 weeks before the onset of symptoms.

Results

A total of 33 patients with severe MIS-C were included (21 male) with a median age of 9 years. The most common signs and symptoms during disease course were fever (100%) and abdominal pain (75.5%). Clinical features of 63.6% patients were consistent with Kawasaki disease/Kawasaki disease shock syndrome, and 36.4% were consistent with secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Myocardial dysfunction and/or coronary artery abnormalities were detected in 18 patients during the PICU stay. Intravenous immunoglobulin and corticosteroids were given to 33 patients. Anakinra was administered to 23 patients (69.6%). There was a significant increase in lymphocyte and platelet counts and a significant decrease in ferritin, B-type natriuretic peptide, and troponin levels at the end of the first week of treatment in patients who were given biological therapy. Two patients were switched to tocilizumab because of an insufficient response to anakinra. The mortality rate of MIS-C patients admitted in PICU was 6.0%.

Conclusions

Management of systemic inflammation and shock is important to decrease mortality and the development of persistent cardiac dysfunction in MIS-C. The aggressive treatment approach, including biological agents, may be required in patients with severe symptoms and cardiac dysfunction.
Effect of Short-term Homebased Pre- and Postoperative Exercise on Recovery After Colorectal Cancer Surgery (PHYSSURG-C)
Authors: Onerup Aron , Andersson John , Angenete Eva , Bock David , Börjesson Mats , Ehrencrona Carolina , Fagevik Olsén Monika , Larsson Per-Anders , de la Croix Hanna , Wedin Anette , Haglind Eva
Published: April 2021

Objective:

To determine the effect of a short-term, unsupervised exercise intervention before and after colorectal cancer surgery on self-assessed physical recovery.

Summary of Background Data:

Preoperative exercise interventions could help improve recovery after colorectal cancer surgery and is currently recommended.

Methods:

A randomized, parallel, open-label trial in six university or regional hospitals in Sweden. Inclusion criteria were age ≥20 years and planned elective colorectal cancer surgery. Participants were randomized to either a physical activity intervention with aerobic activity and inspiratory muscle training 2 weeks pre- and 4 weeks postoperatively or usual care. The primary outcome measure was self-assessed physical recovery 4 weeks postoperatively. Analyses were performed according to intention to treat. Outcome assessors were masked regarding the intervention while both participants and physiotherapists were informed due to the nature of the intervention.

Results:

Between January 22, 2015, and May 28, 2020, 761 participants were recruited and assigned to either intervention (I) (n = 379) or control (C) (n = 382). After exclusions 668 participants (I = 317, C = 351) were included in the primary analysis. There was no effect from the intervention on the primary outcome measure (adjusted odds ratio 0.84, 95% confidence interval 0.62–1.15) with 13% and 15% of participants feeling fully physically recovered in I and C, respectively. There were no reported adverse events.

Conclusions:

There was no effect from a physical activity intervention before and after colorectal cancer surgery on short-term self-assessed physical recovery. The results from this study call for reconsiderations regarding current recommendations for preoperative physical activity interventions.
Laparoscopic Paraesophageal Hernia Repair
Authors: Angeramo Cristian A. , Schlottmann Francisco
Published: April 2021

Objective:

This study aimed to compare outcomes after laparoscopic paraesophageal hernia repair (LPEHR) with mesh or primary repair alone.

Summary of Background Data:

High recurrence rates after LPEHR have been reported. Whether the use of mesh improves outcomes remains elusive.

Methods:

A systematic literature search was performed to identify randomized controlled trials (RCTs) comparing LPEHR with mesh repair versus suture repair alone. Early (≤6 months) and late (>6 months) recurrence rates were used as primary endpoints to assess efficacy. Intraoperative complications, overall morbidity, and reoperation rates were used as secondary endpoints to assess safety. A meta-analysis was conducted using relative risks (RR) with 95% confidence intervals (CI) for the analyzed outcomes.

Results:

Seven RCTs comparing mesh (n = 383) versus suture only (n = 352) repair were included for analysis. Patients undergoing LPEHR with mesh reinforcement had similar early (RR = 0.74, 95% CI = 0.26–2.07, P = 0.46) and late (RR = 0.75, 95% CI = 0.27–2.08, P = 0.48) recurrence rates as those with primary repair. Similar recurrence rates were also found when stratifying the analysis by the type of mesh utilized (absorbable and nonabsorbable). Intraoperative complications (RR = 1.03, 95% CI = 0.33–3.28, P = 0.92) and reoperation rates (RR = 0.75, 95% CI = 0.29–1.92, P = 0.45) were also similar in both groups. Overall morbidity, however, was higher after mesh repair with nonabsorbable mesh (RR = 1.45, 95% CI = 1.24–1.71, P < 0.01)

Conclusions:

Patients undergoing LPEHR have similar early and late recurrence rates with either mesh reinforcement or suture only repair, regardless of the type of mesh utilized. Overall morbidity, however, seems to be higher in patients repaired with nonabsorbable mesh.
‘An exceedingly simple, little ecosystem’: Devils Hole, endangered species conservation, and scientific environments
Authors: Brown Kevin C.
Published: April 2021

This article explores the history of the Devils Hole pupfish (
Cyprinodon diabolis
), regarded by scientists as having the smallest range of any vertebrate species in the world, a single 10 × 60 ft pool in the Amargosa Valley of southern Nye County, Nevada, USA. It considers the impact of ‘scientific environments’ on the possibilities for pupfish survival as well as potential human uses of the desert. Scientific environment is defined as the knowledge and conceptualization of the environment produced from particular questions and methods and that influence how a species, habitat or region is managed. Three successive scientific environments have shaped the conservation of the pupfish since the 1890s: the first led by taxonomic analyses of the pupfish, the second by ecological and hydrological investigations of Devils Hole, as well as its surrounding desert, and the third by genetic analysis of pupfish DNA. The science in each era has shaped (and responded to) the way in which federal and state agencies have worked to conserve this critically endangered species. The article contributes to an understanding of how concepts and practices at the heart of ecological sciences develop from, and impact, particular spaces and species.
Molecular characterization of the first human G15 rotavirus strain of zoonotic origin from the bovine species
Authors: Tsugawa Takeshi , Fujii Yoshiki , Akane Yusuke , Honjo Saho , Kondo Kenji , Nihira Hiroshi , Kimura Hirokazu , Kawasaki Yukihiko
Published: April 2021

Group A rotaviruses (RVAs) infect a wide variety of mammalian and avian species. Animals act as a potential reservoir to RVA human infections by direct virion transmission or by contributing genes to reassortants. Here, we report the molecular characterization of a rare human RVA strain Ni17-46 with a genotype G15P[14], isolated in Japan in 2017 during rotavirus surveillance in a paediatric outpatient clinic. The genome constellation of this strain was G15-P[14]-I2-R2-C2-M2-A13-N2-T9-E2-H3. This is the first report of an RVA with G15 genotype in humans, and sequencing and phylogenetic analysis results suggest that human infection with this strain has zoonotic origin from the bovine species. Given the fact that this strain was isolated from a patient with gastroenteritis and dehydration symptoms, we must take into account the virulence of this strain in humans.
Shotgun metagenomics reveals distinct functional diversity and metabolic capabilities between 12 000-year-old permafrost and active layers on Muot da Barba Peider (Swiss Alps)
Authors: Perez-Mon Carla , Qi Weihong , Vikram Surendra , Frossard Aline , Makhalanyane Thulani , Cowan Don , Frey Beat
Published: April 2021

The warming-induced thawing of permafrost promotes microbial activity, often resulting in enhanced greenhouse gas emissions. The ability of permafrost microorganisms to survive the in situ sub-zero temperatures, their energetic strategies and their metabolic versatility in using soil organic materials determine their growth and functionality upon thawing. Hence, functional characterization of the permafrost microbiome, particularly in the underexplored mid-latitudinal alpine regions, is a crucial first step in predicting its responses to the changing climate, and the consequences for soil–climate feedbacks. In this study, for the first time, the functional potential and metabolic capabilities of a temperate mountain permafrost microbiome from central Europe has been analysed using shotgun metagenomics. Permafrost and active layers from the summit of Muot da Barba Peider (MBP) [Swiss Alps, 2979 m above sea level (a.s.l.)] revealed a strikingly high functional diversity in the permafrost (north-facing soils at a depth of 160 cm). Permafrost metagenomes were enriched in stress-response genes (e.g. cold-shock genes, chaperones), as well as in genes involved in cell defence and competition (e.g. antiviral proteins, antibiotics, motility, nutrient-uptake ABC transporters), compared with active-layer metagenomes. Permafrost also showed a higher potential for the synthesis of carbohydrate-active enzymes, and an overrepresentation of genes involved in fermentation, carbon fixation, denitrification and nitrogen reduction reactions. Collectively, these findings demonstrate the potential capabilities of permafrost microorganisms to thrive in cold and oligotrophic conditions, and highlight their metabolic versatility in carbon and nitrogen cycling. Our study provides a first insight into the high functional gene diversity of the central European mountain permafrost microbiome. Our findings extend our understanding of the microbial ecology of permafrost and represent a baseline for future investigations comparing the functional profiles of permafrost microbial communities at different latitudes.
COLI-NET: Fully Automated COVID-19 Lung and Infection Pneumonia Lesion Detection and Segmentation from Chest CT Images
Authors: Shiri Isaac , Arabi Hossein , Salimi Yazdan , Sanaat Amir Hossein , Akhavanalaf Azadeh , Hajianfar Ghasem , Askari Dariush , Moradi Shakiba , Mansouri Zahra , Pakbin Masoumeh , Sandoughdaran Saleh , Abdollahi Hamid , Radmard Amir Reza , Rezaei-Kalantari Kiara , Oghli Mostafa Ghelich , Zaidi Habib
Published: April 2021

Background

We present a deep learning (DL)-based automated whole lung and COVID-19 pneumonia infectious lesions (COLI-Net) detection and segmentation from chest CT images.

Methods

We prepared 2358 (347’259, 2D slices) and 180 (17341, 2D slices) volumetric CT images along with their corresponding manual segmentation of lungs and lesions, respectively, in the framework of a multi-center/multi-scanner study. All images were cropped, resized and the intensity values clipped and normalized. A residual network (ResNet) with non-square Dice loss function built upon TensorFlow was employed. The accuracy of lung and COVID-19 lesions segmentation was evaluated on an external RT-PCR positive COVID-19 dataset (7’333, 2D slices) collected at five different centers. To evaluate the segmentation performance, we calculated different quantitative metrics, including radiomic features.

Results

The mean Dice coefficients were 0.98±0.011 (95% CI, 0.98-0.99) and 0.91±0.038 (95% CI, 0.90-0.91) for lung and lesions segmentation, respectively. The mean relative Hounsfield unit differences were 0.03±0.84% (95% CI, −0.12 – 0.18) and −0.18±3.4% (95% CI, −0.8 - 0.44) for the lung and lesions, respectively. The relative volume difference for lung and lesions were 0.38±1.2% (95% CI, 0.16-0.59) and 0.81±6.6% (95% CI, −0.39-2), respectively. Most radiomic features had a mean relative error less than 5% with the highest mean relative error achieved for the lung for theRangefirst-order feature (- 6.95%) andleast axis lengthshape feature (8.68%) for lesions.

Conclusion

We set out to develop an automated deep learning-guided three-dimensional whole lung and infected regions segmentation in COVID-19 patients in order to develop fast, consistent, robust and human error immune framework for lung and pneumonia lesion detection and quantification.
The association between blast exposure and transdiagnostic health symptoms on systemic inflammation
Authors: Hayes Jasmeet P. , Pierce Meghan E. , Valerio Kate E. , Miller Mark , Russell Huber Bertrand , Fortier Catherine B. , Fonda Jennifer R. , Milberg William , McGlinchey Regina
Published: April 2021

Chronic elevation of systemic inflammation is observed in a wide range of disorders including PTSD, depression, and traumatic brain injury, all of which are relatively common in United States Veterans. Although previous work has demonstrated a link between inflammation and various diagnoses separately, few studies have examined transdiagnostic symptoms and inflammation within the same model. The objective of this study was to examine relationships between psychiatric and health variables and systemic inflammation, and to determine whether mild traumatic brain injury (mTBI) and/or exposure to blast munitions moderate these relationships. Confirmatory factor analysis in a large sample (N = 357) of post-9/11 Veterans demonstrated good fit to a four-factor model reflecting traumatic stress, affective, somatic, and metabolic latent variables. Hierarchical regression models revealed that each of the latent variables were associated with higher levels of systemic inflammation. However, the strongest relationship with inflammation emerged among those who had both war-zone blast exposures and metabolic dysregulation, even after adjusting for mental health latent variables. Exploratory analyses showed that blast exposure was associated with metabolic dysregulation in a dose-response manner, with self-reported closer blast proximity associated with the greatest metabolic dysregulation. Together, these results provide greater understanding of the types of symptoms most strongly associated with inflammation, and underscore the importance of maintaining a healthy lifestyle to reduce the impact of obesity and other metabolic symptoms on future chronic disease in younger to middle-aged Veterans.
Improving SARS-CoV-2 cumulative incidence estimation through mixture modelling of antibody levels
Authors: Bottomley C. , Otiende M. , Uyoga S. , Gallagher K. , Kagucia E.W. , Etyang A.O. , Mugo D. , Gitonga J. , Karanja H. , Nyagwange J. , Adetifa I.M.O. , Agweyu A. , Nokes D.J. , Warimwe G.M. , Scott J.A.G.
Published: April 2021

As countries decide on vaccination strategies and how to ease movement restrictions, estimates of cumulative incidence of SARS-CoV-2 infection are essential in quantifying the extent to which populations remain susceptible to COVID-19. Cumulative incidence is usually estimated from seroprevalence data, where seropositives are defined by an arbitrary threshold antibody level, and adjusted for sensitivity and specificity at that threshold. This does not account for antibody waning nor for lower antibody levels in asymptomatic or mildly symptomatic cases. Mixture modelling can estimate cumulative incidence from antibody-level distributions without requiring adjustment for sensitivity and specificity. To illustrate the bias in standard threshold-based seroprevalence estimates, we compared both approaches using data from several Kenyan serosurveys. Compared to the mixture model estimate, threshold analysis underestimated cumulative incidence by 31% (IQR: 11 to 41) on average. Until more discriminating assays are available, mixture modelling offers an approach to reduce bias in estimates of cumulative incidence.

One-Sentence Summary

Mixture models reduce biases inherent in the standard threshold-based analysis of SARS-CoV-2 serological data.
Addressing child health inequity through case management of under-five malaria in Nigeria: A model-based extended cost-effectiveness analysis
Authors: Dasgupta Rishav Raj , Mao Wenhui , Ogbuoji Osondu
Published: April 2021

Background

Under-five malaria in Nigeria remains one of the biggest threats to global child health, accounting for 95,000 annual child deaths. Despite having the highest GDP in Africa, Nigeria’s current health financing system has not succeeded in reducing high out-of-pocket medical expenditure, which discourages care-seeking and use of effective antimalarials in the poorest households. Resultingly, Nigeria has some of the worst indicators of child health equity among low and middle-income countries, stressing the need to evaluate how the benefits of health interventions are distributed across socioeconomic lines.

Methods

We developed a decision tree model for case management of under-five malaria in Nigeria and conducted an extended cost-effectiveness analysis of subsidies covering the direct and indirect costs of treatment. We estimated the number of under-five malaria deaths averted, out-of-pocket (OOP) expenditure averted, cases of catastrophic health expenditure (CHE) averted, and cost of implementation.

Finding

Fully subsidizing direct medical costs plus a voucher system to cover non-medical and indirect costs with pro-poor increase in treatment coverage would annually avert over 19,000 under-five deaths, US$205.2 million in OOP spending, and 8,600 cases of CHE. Per US$1 million invested, this corresponds to 76 under-five deaths averted, 34 cases of CHE averted, and over US$800,000 in OOP expenditure averted. Due to low current treatment coverage and high disease burden, the health and financial-risk protection benefits would be pro-poor, with the poorest 40% of Nigerians accounting for 72% of all deaths averted, 55% of all OOP expenditure averted, and 74% of all cases of CHE averted. Targeted subsidies to the poor would see significantly greater health and economic benefits per US$1 million invested than broad, non-targeted interventions.

Conclusion

Subsidizing case management of under-five malaria for the poorest and most vulnerable children would significantly reduce illness-related impoverishment and child mortality in Nigeria while preserving limited financial resources.
Constructing germline research cohorts from the discarded reads of clinical tumor sequences
Authors: Gusev Alexander , Groha Stefan , Taraszka Kodi , Semenov Yevgeniy R. , Zaitlen Noah
Published: April 2021

Background

Hundreds of thousands of cancer patients have had targeted (panel) tumor sequencing to identify clinically meaningful mutations. In addition to improving patient outcomes, this activity has led to significant discoveries in basic and translational domains. However, the targeted nature of clinical tumor sequencing has a limited scope, especially for germline genetics. In this work, we assess the utility of discarded, off-target reads from tumor-only panel sequencing for recovery of genome-wide germline genotypes through imputation.

Methods

We develop a framework for inference of germline variants from tumor panel sequencing, including imputation, quality control, inference of genetic ancestry, germline polygenic risk scores, and HLA alleles. We benchmark our framework on 833 individuals with tumor sequencing and matched germline SNP array data. We then apply our approach to a prospectively collected panel sequencing cohort of 25,889 tumors.

Results

We demonstrate high to moderate accuracy of each inferred feature relative to direct germline SNP array genotyping: individual common variants were imputed with a mean accuracy (correlation) of 0.86; genetic ancestry was inferred with a correlation of >0.98; polygenic risk scores were inferred with a correlation of >0.90; and individual HLA alleles were inferred with correlation of >0.89. We demonstrate a minimal influence on accuracy of somatic copy number alterations and other tumor features. We showcase the feasibility and utility of our framework by analyzing 25,889 tumors and identifying relationships between genetic ancestry, polygenic risk, and tumor characteristics that could not be studied with conventional data.

Conclusions

We conclude that targeted tumor sequencing can be leveraged to build rich germline research cohorts from existing data, and make our analysis pipeline publicly available to facilitate this effort.
New Insight into the Neural Mechanisms of Migraine in Adolescents: Relationships with Sleep
Authors: Nahman-Averbuch Hadas , Schneider Victor J , Lee Gregory R. , Peugh James L. , Hershey Andrew D. , Powers Scott W. , de Zambotti Massimiliano , Coghill Robert C. , King Christopher D.
Published: April 2021

Adolescents with migraine have different functional connectivity of the amygdala compared to individuals without migraine. Considering that sleep is often disturbed in those adolescents with migrane, this study examined if measures of subjective and objective (actigraphic) sleep difficulties mediate alterations in amygdalar connectivity in adolescents with migraine compared to healthy adolescents. Twenty adolescents with migraine and 20 healthy controls completed surveys about their headaches and overall sleep quality, sleep hygiene and perceived sleep difficulties, wore a wrist-worn actigraphy, and underwent an MRI scan.

Adolescents with migraine differed from healthy controls only in perceived sleep difficulties related to sleep initiation and maintenance (p<0.01) and had greater functional connectivity between the amygdala and the posterior cingulate cortex, precuneus, dorsolateral prefrontal, sensorimotor, and the occipital cortexes. While the mediation model showed group differences in subjective and actigraphic sleep difficulties, these did not mediate the differences in amygdalar connectivity found between the groups. Adolescents with migraine have greater connectivity between the amygdala and areas involved in sensory, affective, and cognitive aspects of pain. These alterations may not be due to higher levels of sleep difficulties in adolescents with migraine, suggesting that both amygdala and sleep alterations may play an independent role in migraine pathophysiology

Perspective

This article evaluates the role plays by sleep on neural alterations in adolescents with migraine. It indicates that neural alterations due to migraine are not related to alterations in subjective and actigraphic sleep difficulties. This advances the understanding of the mechanisms underlying pediatric migraine and can potentially advance migraine management.
COVID-19 vaccine perceptions: An observational study on Reddit
Authors: Kumar Navin , Corpus Isabel , Hans Meher , Harle Nikhil , Yang Nan , McDonald Curtis , Sakai Shinpei Nakamura , Janmohamed Kamila , Tang Weiming , Schwartz Jason L. , Jones-Jang S. Mo , Saha Koustuv , Memon Shahan Ali , Bauch Chris T. , De Choudhury Munmun , Papakyriakopoulos Orestis , Tucker Joseph D. , Goyal Abhay , Tyagi Aman , Khoshnood Kaveh , Omer Saad
Published: April 2021

Objectives

As COVID-19 vaccinations accelerate in many countries, narratives skeptical of vaccination have also spread through social media. Open online forums like Reddit provide an opportunity to quantitatively examine COVID-19 vaccine perceptions over time. We examine COVID-19 misinformation on Reddit following vaccine scientific announcements.

Methods

We collected all posts on Reddit from January 1 2020 - December 14 2020 (n=266,840) that contained both COVID-19 and vaccine-related keywords. We used topic modeling to understand changes in word prevalence within topics after the release of vaccine trial data. Social network analysis was also conducted to determine the relationship between Reddit communities (subreddits) that shared COVID-19 vaccine posts, and the movement of posts between subreddits.

Results

There was an association between a Pfizer press release reporting 90% efficacy and increased discussion on vaccine misinformation. We observed an association between Johnson and Johnson temporarily halting its vaccine trials and reduced misinformation. We found that information skeptical of vaccination was first posted in a subreddit (r/Coronavirus) which favored accurate information and then reposted in subreddits associated with antivaccine beliefs and conspiracy theories (e.g. conspiracy, LockdownSkepticism).

Conclusions

Our findings can inform the development of interventions where individuals determine the accuracy of vaccine information, and communications campaigns to improve COVID-19 vaccine perceptions. Such efforts can increase individual- and population-level awareness of accurate and scientifically sound information regarding vaccines and thereby improve attitudes about vaccines. Further research is needed to understand how social media can contribute to COVID-19 vaccination services.

Funding

Study was funded by the Yale Institute for Global Health and the Whitney and Betty MacMillan Center for International and Area Studies at Yale University. The funding bodies had no role in the design, analysis or interpretation of the data in the study.
Inpatient outcomes for hospitalized older adults with rhinovirus
Authors: Del Corpo Olivier , McDonald Emily G. , Smyth Luisa , Smyth Elizabeth , Walji Moneeza , Cheng Matthew P. , Frenette Charles , Saleh Ramy R. , Lee Todd C.
Published: April 2021

Background

Rhinoviruses account for many cases of the “common cold” and infection is often self-limiting. As such, there is a lack of data regarding the inpatient outcomes of individuals hospitalized with rhinovirus infection. Given the generalized poorer prognosis of elderly admitted with respiratory viral infections, we assessed the mortality rate of general medical patients admitted with rhinovirus infection along with the major risk factors associated to mortality.

Methods

We performed a retrospective chart review of patients admitted to our clinical teaching ward from December 2013 to June 2017.

Results

Overall, 12.5% of patients admitted with rhinovirus infection died within 90 days of admission. The median age of admitted patients was 70 years-old. In univariable analysis, age (OR 1.05; 95% confidence interval (CI) 1.01-1.09) and the need for oxygen at presentation (OR 3.23; 95% CI 1.06-9.86) were associated with death while obstructive pulmonary disease or asthma (OR 0.10; 95% CI 0.01-0.81) was associated with survival. In the multivariable model, age (aOR 1.04; 95% CI 1.00-1.09) and obstructive lung disease (aOR 0.09 95%CI 0.01-0.73) remained significant whereas the requirement for oxygen at presentation did not (aOR 2.78; 95% CI 0.84-9.23).

Conclusion

Our study reveals that rhinovirus is an important cause of both morbidity and mortality in the elderly and further highlights the need for studies of potentially effective treatment options. In the meantime, we suggest that rigorous respiratory hygiene measures and quality older adult care should be practiced when caring for at-risk adults.
Prevalence, awareness, treatment, and control of hypertension in Bangladesh: Findings from National Demographic and Health Survey, 2017-18
Authors: Khan Md. Nuruzzaman , Oldroyd John C. , Chowdhury Enayet K. , Hossain Mohammad Bellal , Rana Juwel , Renzetti Stefano , Islam Rakibul M.
Published: April 2021

Objective

To estimate the age-standardised prevalence, awareness, treatment, and control of hypertension and to identify their risk factors in Bangladeshi adults using the Bangladesh Demographic and Health Survey (BDHS) 2017-18 data.

Methods

Data from 12, 904 adults aged 18-95 years old, median (IQR) = 36 years (26-50), available from the most recent nationally representative BDHS 2017-18 were used. Hypertension was defined as having systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg, and/or taking anti-hypertensive drugs to control blood pressure. Age-standardised prevalence of hypertension and management were estimated with direct standardisation. A multilevel mixed-effects Poisson regression model with a robust variance was used to identify risk factors associated with hypertension and its awareness, treatment, and control.

Results

The overall age-standardised prevalence of hypertension was 26.2% (95% CI, 25.5-26.9); (men: 23.5%, women: 28.9%). Among those with hypertension (n=3531), 36.7% were aware that they had the condition, and only 31.1% received anti-hypertensive medication. Among those treated for hypertension (n=1306), 43.6% had controlled hypertension. Factors independently associated with hypertension were increasing age, higher body mass index, being women, having diabetes, and residing in selected administrative divisions. A declining trend of hypertension control was observed with increasing age and low education.

Conclusions

Hypertension is highly prevalent (1 in 4) in Bangladeshi adults, while awareness, treatment, and control are low. Irrespective of the risks associated with hypertension and its management, awareness, treatment, and control programmes should be given high priority in reducing hypertension and improving hypertension control in Bangladesh.
Detection of conspicuous and cryptic food by marmosets (Callithrix jacchus): An evaluation of the importance of color and shape cues
Authors: Barros Priscilla Kelly Silva , Castro Felipe Nalon , Pessoa Daniel Marques Almeida
Published: April 2021

Since 19th century, the adaptive function of color vision for object identification has fascinated science. Countless articles uncovered the advantages of trichromacy (i.e., color vision expressed by most humans) in detecting yellowish/reddish targets against a background of mature green leaves. Unfortunately, the same attention was not offered to achromatic visual information, that had their physiological foundations much more explored than their possible adaptive function. So far, mostly because of studies conducted in humans, we know that achromatic cues might also play an important role in object identification, particularly when camouflage is involved. For instance, dichromacy (i.e., color vision expressed by many colorblind humans), favors the detection of camouflaged targets by exploitation of shape cues. The present study sought to evaluate the relative importance of color and shape cues on the detection of food targets by female and male marmosets (Callithrix jacchus). Animals were observed with respect to their foraging behavior and the number of food targets captured. We confirmed that females are advantageous in detecting conspicuous food against a green background and revealed that females and males rely on shape cues to segregate cryptic food. Unexpectedly, males outperformed females in cryptic food foraging. Camouflage improved males’ (but not females’) performance.

Highlights

Shape cues alone improve capture of cryptic targets by female and male marmosets.

The sole use of color cues leads to clear-cut foraging performances between sex.

Females outperform males when searching for orange food against a green background.

Males outperform females when searching for green food against a green background.

Males match females’ performance when searching for orange camouflaged food.
ALS and FTD-associated missense mutations in TBK1 differentially disrupt mitophagy
Authors: Harding Olivia , Evans Chantell S. , Ye Junqiang , Cheung Jonah , Maniatis Tom , Holzbaur Erika L.F.
Published: April 2021

TANK-binding kinase 1 (TBK1) is a multi-functional kinase with an essential role in mitophagy, the selective clearance of damaged mitochondria. More than 90 distinct mutations in TBK1 are linked to amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD), including missense mutations that disrupt the ability of TBK1 to dimerize, associate with the mitophagy receptor optineurin (OPTN), auto-activate, or catalyze phosphorylation. We investigated how ALS-associated mutations in TBK1 affect Parkin-dependent mitophagy using imaging to dissect the molecular mechanisms involved in clearing damaged mitochondria. Some mutations cause severe dysregulation of the pathway, while others induce limited disruption. Mutations that abolish either TBK1 dimerization or kinase activity were insufficient to fully inhibit mitophagy, while mutations that reduced both dimerization and kinase activity were more disruptive. Ultimately, both TBK1 recruitment and OPTN phosphorylation at S177 are necessary for engulfment of damaged mitochondra by autophagosomal membranes. Surprisingly, we find that ULK1 activity contributes to the phosphorylation of OPTN in the presense of either WT- or kinase inactive TBK1. In primary neurons, TBK1 mutants induce mitochondrial stress under basal conditions; network stress is exacerbated with further mitochondrial insult. Our study further refines the model for TBK1 function in mitophagy, demonstrating that some ALS-linked mutations likely contribute to disease pathogenesis by inducing mitochondrial stress or inhibiting mitophagic flux. Other TBK1 mutations exhibited much less impact on mitophagy in our assays, suggesting that cell-type specific effects, cumulative damage, or alternative TBK1-dependent pathways such as innate immunity and inflammation also factor into the development of ALS in affected individuals.

SIGNIFICANCE STATEMENT

Missense mutations in TANK-binding kinase 1 (TBK1) have various biophysical and biochemical effects on the molecule, and are associated with the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD). TBK1 plays an essential role in clearing damaged mitochondria. Here, we investigate the impact of 10 ALS-linked TBK1 mutations on the critical early stage of mitophagy. We find that both TBK1 recruitment and kinase activity contribute to the clearance of the damaged mitochondria. Furthermore, in neurons, expression of TBK1 mutants alone affects mitochondrial network health. Our investigation utilizes disease-linked mutations to further refine the current model of mitophagy, identifying crosstalk between the regulatory kinases TBK1 and ULK1, and providing new insights into the roles of TBK1 in neurodegenerative pathogenesis.
Impairment of SARS-CoV-2 spike-glycoprotein maturation and fusion-activity by nitazoxanide: an effect independent of spike variants emergence
Authors: Riccio Anna , Santopolo Silvia , Rossi Antonio , Piacentini Sara , Rossignol Jean-Francois , Santoro M. Gabriella
Published: April 2021

SARS-CoV-2, the causative agent of COVID-19, has caused an unprecedented global health crisis. The SARS-CoV-2 spike, a surface-anchored trimeric class-I fusion-glycoprotein essential for viral entry, represents a key target for developing vaccines and therapeutics capable of blocking virus invasion. The emergence of SARS-CoV-2 spike-variants that facilitate virus spread and may affect vaccine efficacy highlights the need to identify novel antiviral strategies for COVID-19 therapy. Here we demonstrate that nitazoxanide, an antiprotozoal agent with recognized broad-spectrum antiviral activity, interferes with SARS-CoV-2 spike biogenesis, hampering its maturation at an endoglycosidase H-sensitive stage. Engineering multiple SARS-CoV-2 variant-pseudoviruses and utilizing quantitative cell-cell fusion assays, we show that nitazoxanide-induced spike modifications hinder progeny virion infectivity as well as spike-driven pulmonary cell-cell fusion, a critical feature of COVID-19 pathology. Nitazoxanide, being equally effective against the ancestral SARS-CoV-2 Wuhan-spike and different emerging variants, including the Delta variant of concern, may represent a useful tool in the fight against COVID-19 infections.
Mutation rate dynamics reflect ecological change in an emerging zoonotic pathogen
Authors: Murray Gemma G. R. , Balmer Andrew J. , Herbert Josephine , Hadijirin Nazreen F. , Kemp Caroline L. , Matuszewska Marta , Bruchmann Sebastian , Mukarram Hossain A. S. Md. , Gottschalk Marcelo , Tucker A. W. (Dan) , Miller Eric , Weinert Lucy A.
Published: April 2021

While mutation is often deleterious, it can also be adaptive. Mutation rates vary both within and between bacterial species, and understanding what drives this variation is essential for understanding the evolutionary dynamics of bacterial populations. In this study we investigate two factors that are predicted to influence the trade-off between the costs and benefits of mutation: ecology and genome size. To investigate the relationship between these factors and mutation rate we conducted mutation accumulation experiments on eight strains of the emerging zoonotic pathogenStreptococcus suis. Natural variation within this species allows us to compare tonsil carriage and invasive disease isolates, from both more and less pathogenic populations, with a wide range of genome sizes. We find that invasive disease isolates have repeatedly evolved mutation rates that are higher than those of closely related carriage isolates, regardless of variation in genome size. Independent of this variation in overall rate, we also observe a stronger bias towards G/C to A/T mutations in isolates from more pathogenic populations, whose genomes tend to be smaller and more AT-rich. Our results suggest that ecology is a stronger correlate of mutation rate than genome size over these timescales, and that transitions to invasive disease are consistently accompanied by rapid increases in mutation rate. These results shed light on the impact ecology can have on the adaptive potential of bacterial pathogens.
Activation of innate immune signalling during development predisposes to inflammatory intestine and shortened lifespan
Authors: Yamashita Kyoko , Oi Ayano , Kosakamoto Hina , Yamauchi Toshitaka , Kadoguchi Hibiki , Kuraishi Takayuki , Miura Masayuki , Obata Fumiaki
Published: April 2021

Early-life inflammatory response is associated with risks of age-related pathologies. How transient immune signalling activity during animal development influences life-long fitness is not well understood. UsingDrosophilaas a model, we find that activation of innate immune pathway IMD signalling in the developing larvae increases adult starvation resistance, decreases food intake, and shortens organismal lifespan. Interestingly, lifespan is shortened by the IMD activation in the larval gut and fat body, while starvation resistance and food intake are altered by that in neurons. The adult flies developed with IMD activation show sustained IMD activity in the gut, despite complete tissue renewal during metamorphosis. The inflammatory adult gut is associated with a greater amount ofGluconobactersp., characteristic gut microbiota increased in response to immune activation. Removing gut microbiota by antibiotics attenuates the increase of IMD activity and rescues the shortened lifespan. This study demonstrates a tissue-specific programming effect of early-life immune activation on the adult physiology and organismal lifespan.
How basic components of information-updating interact to encourage variation in the results of empirical studies of within and transgenerational plasticity
Authors: Stamps Judy A , Bell Alison M
Published: April 2021

Experiences of parents and/or offspring are often assumed to affect the development of trait values in offspring because they provide information about the external environment, but it is currently unclear how information from different sources and times might combine to affect the information-states that provide the foundation for the patterns observed in empirical studies of developmental plasticity in response to environmental cues. We analyze Bayesian models designed to mimic fully-factorial experimental studies of within and transgenerational plasticity (TWP), in which parents, offspring, neither or both are exposed to cues from predators, to determine how different durations of cue exposure for parents and offspring, the devaluation of information from parents or the degradation of information from parents would affect offspring estimates of environmental states related to risk of predation at the end of such experiments. We show that the effects of different cue durations, the devaluation of information from parents, and the degradation of information from parents on offspring estimates are all expected to vary as a function of interactions with two other key parameters of information-based models of TWP: parental priors and the relative cue reliability in the different treatments. Our results suggest empiricists should expect to observe considerable variation across experimental studies of TWP based on simple principles of information-updating, without needing to invoke additional assumptions about costs, tradeoffs, development constraints, the fitness consequences of different trait values, or other factors.
The world’s hotspot of linguistic and biocultural diversity under threat
Authors: Kik Alfred , Adamec Martin , Aikhenvald Alexandra Y. , Bajzekova Jarmila , Baro Nigel , Bowern Claire , Colwell Robert K. , Drozd Pavel , Duda Pavel , Ibalim Sentiko , Jorge Leonardo R. , Mogina Jane , Ruli Ben , Sam Katerina , Sarvasy Hannah , Saulei Simon , Weiblen George D. , Zrzavy Jan , Novotny Vojtech
Published: April 2021

Papua New Guinea is home to >10% of the world’s languages and rich and varied biocultural knowledge, but the future of this diversity remains unclear. We measured language skills of 6,190 students speaking 392 languages (5.5% of the global total) and modelled their future trends, using individual-level variables characterizing family language use, socio-economic conditions, student’s skills, and language traits. This approach showed that only 58% of the students, compared to 91% of their parents, were fluent in indigenous languages, while the trends in key drivers of language skills (language use at home, proportion of mixed-language families, urbanization, students’ traditional skills) predicted accelerating decline of fluency, to an estimated 26% in the next generation of students. Ethnobiological knowledge declined in close parallel with language skills. Varied medicinal plant uses known to the students speaking indigenous languages are replaced by a few, mostly non-native species for the students speaking English or Tok Pisin, the national lingua franca. Most (88%) students want to teach indigenous language to their children. While crucial for keeping languages alive, this intention faces powerful external pressures as key factors (education, cash economy, road networks, urbanization) associated with language attrition are valued in contemporary society.

Significance Statement

Around the world, more than 7,000 languages are spoken, most of them by small populations of speakers in the tropics. Globalization puts small languages at a disadvantage, but our understanding of the drivers and rate of language loss remains incomplete. When we tested key factors causing language attrition among Papua New Guinean students speaking 392 different indigenous languages, we found an unexpectedly rapid decline in their language skills compared to their parents and predicted further acceleration of language loss in the next generation. Language attrition was accompanied by decline in the traditional knowledge of nature among the students, pointing to an uncertain future for languages and biocultural knowledge in the most linguistically diverse place on Earth.
YTHDC2 Is Essential for Pachytene Progression and Prevents Aberrant Microtubule-Driven Telomere Clustering in Male Meiosis
Authors: Liu Rong , Kasowitz Seth D. , Homolka David , Leu N. Adrian , Shaked Jordan T. , Ruthel Gordon , Jain Devanshi , Keeney Scott , Luo Mengcheng , Pillai Ramesh S. , Wang P. Jeremy
Published: April 2021

Mechanisms driving the prolonged meiotic prophase I are poorly understood. The RNA helicase YTHDC2 is critical for mitosis to meiosis transition, as YTHDC2-deficient mouse germ cells initiate meiosis but arrest with mixed characteristics of mitotic and meiotic cell types. However, YTHDC2 is also highly expressed in normal pachytene cells. Here we identify an essential role for YTHDC2 in meiotic progression. Specifically, we find that YTHDC2 deficiency causes microtubule-dependent telomere clustering and apoptosis at the pachytene stage of prophase I, and thus a failure to advance to the diplotene stage. Depletion of YTHDC2 results in a massively dysregulated transcriptome in pachytene cells, with a tendency toward upregulation of genes normally expressed in mitotic germ cells and downregulation of meiotic transcripts. Dysregulation does not correlate with the m6A status of RNAs and YTHDC2-bound mRNAs are enriched in genes upregulated in mutant germ cells, revealing that YTHDC2 primarily targets its substrate mRNAs for degradation. Finally, altered transcripts in YTHDC2-deficient pachytene cells encode microtubule network proteins and inhibition of microtubule polymerization disperses clustered telomeres. Together, our results demonstrate that YTHDC2 regulates the prolonged pachytene stage of prophase I by perpetuating a meiotic transcriptome and preventing changes in the microtubule network that could lead to aberrant telomere clustering.
Modelling the impact of magnesium ions concentration on the folding of the SAM-II riboswitch
Authors: Alaidi Osama
Published: April 2021

Riboswitches are regulatory elements present in bacterial messenger RNA acting as sensors of small molecules and consequently playing a vital role in bacterial gene regulation. The SAM-II riboswitch is a class of riboswitches, that recognizes S-adenosyl methionine. It has been previously illustrated that the presence of Mg2+ions stabilizes the pre-existing minor state of the riboswitch, which is structurally characterised by having a nucleated pseudoknot, leading to the increase of its probability. In this study, an analytical equilibrium model is developed to describe the impact of Mg2+ions concentration on the folding of the SAM-II riboswitch, linking RNA folding and tertiary interactions energetics to ligand binding, and, hence enabling quantitative predictions. The method was used to study the role of the P1 helix sequence in determining the fraction of binding competent conformers of the SAM-II riboswitch, by simulating the Mg2+titration curves of various mutants.

Graphical abstract