bluuebunny/crossref_metadata_2025 huggingface dataset:
A regulatory sub-circuit downstream of Wnt signaling controls developmental transitions in neural crest formation
Authors: Azambuja Ana Paula , Simoes-Costa Marcos
Published: January 2021

The process of cell fate commitment involves sequential changes in the gene expression profiles of embryonic progenitors. This is exemplified in the development of the neural crest, a migratory stem cell population derived from the ectoderm of vertebrate embryos. During neural crest formation, cells transition through distinct transcriptional states in a stepwise manner. The mechanisms underpinning these shifts in cell identity are still poorly understood. Here we employ enhancer analysis to identify a genetic sub-circuit that controls developmental transitions in the nascent neural crest. This sub-circuit links Wnt target genes in an incoherent feedforward loop that controls the sequential activation of genes in the neural crest lineage. By examining the cis-regulatory apparatus of Wnt effector gene AXUD1, we found that multipotency factor SP5 directly promotes neural plate border identity, while inhibiting premature expression of specification genes. Our results highlight the importance of repressive interactions in the neural crest gene regulatory network and illustrate how genes activated by the same upstream signal become temporally segregated during progressive fate restriction.
High endemicity of alveolar echinococcosis in Yili Prefecture, Xinjiang Autonomous Region, the People’s Republic of China: Infection status in different ethnic communities and in small mammals
Authors: Guo Baoping , Zhang Zhuangzhi , Guo Yongzhong , Guo Gang , Wang Haiyan , Ma Jianjun , Chen Ronggui , Zheng Xueting , Bao Jianling , He Li , Wang Tian , Qi Wenjing , Tian Mengxiao , Wang Junwei , Zhou Canlin , Giraudoux Patrick , Marston Christopher G. , McManus Donald P. , Zhang Wenbao , Li Jun
Published: January 2021

Alveolar echinococcosis (AE) is a life-threatening disease in humans caused by the larval stage ofEchinococcus multilocularis. The tapeworm is transmitted between small mammals and dogs/foxes in the Northern Hemisphere. In this study 286 AE cases were reported from eight counties and one city in Yili Prefecture, Xinjiang Autonomous Region, the People’s Republic of China from 1989 to 2015 with an annual incidence (AI) of 0.41/100,000. Among the patients, 73.08% were diagnosed in the last 11 years. Four counties in the high mountainous areas showed higher AI (0.51–1.22 cases/100,000 residents) than the four counties in low level areas (0.19–0.29/100,000 residents). The AI of AE in Mongolian (2.06/100,000 residents) and Kazak (0.93/100,000 residents) ethnic groups was higher than the incidence in other ethnic groups indicating sheep-farming is a risk for infection given this activity is mainly practiced by these two groups in the prefecture. A total of 1411 small mammals were captured with 9.14% infected withE.multilocularismetacestodes.Microtus obscuruswas the dominant species in the mountain pasture areas with 15.01% of the voles infected, whereasMus musculusandApodemus sylvaticuswere the dominant small mammals in the low altitude areas. Only 0.40% ofA.sylvaticuswere infected withE.multilocularis. PCR amplification and sequencing analysis of the mitochondrialcox1gene showed thatE.multilocularisDNA sequences from the small mammals were identical to isolates of local human AE cases. The overall results show that Yili Prefecture is a highly endemic area for AE and that the high-altitude pasture areas favorable forM.obscurusmay play an important role in its transmission in this region.
Insecticide-treated house screening protects against Zika-infected Aedes aegypti in Merida, Mexico
Authors: Manrique-Saide Pablo , Herrera-Bojórquez Josué , Medina-Barreiro Anuar , Trujillo-Peña Emilio , Villegas-Chim Josué , Valadez-González Nina , Ahmed Ahmed M. M. , Delfín-González Hugo , Palacio-Vargas Jorge , Che-Mendoza Azael , Pavía-Ruz Norma , Flores Adriana E. , Vazquez-Prokopec Gonzalo
Published: January 2021

Background

The integration of house-screening and long-lasting insecticidal nets, known as insecticide-treated screening (ITS), can provide simple, safe, and low-tech Aedes aegypti control. Cluster randomised controlled trials in two endemic localities for Ae. aegypti of south Mexico, showed that ITS conferred both, immediate and sustained (~2 yr) impact on indoor-female Ae. aegypti infestations. Such encouraging results require further validation with studies quantifying more epidemiologically-related endpoints, including arbovirus infection in Ae. aegypti. We evaluated the efficacy of protecting houses with ITS on Ae. aegypti infestation and arbovirus infection during a Zika outbreak in Merida, Yucatan, Mexico.

Methodology/Principal findings

A two-arm cluster-randomised controlled trial evaluated the entomological efficacy of ITS compared to the absence of ITS (with both arms able to receive routine arbovirus vector control) in the neighbourhood Juan Pablo II of Merida. Cross-sectional entomological surveys quantified indoor adult mosquito infestation and arbovirus infection at baseline (pre-ITS installation) and throughout two post-intervention (PI) surveys spaced at 6-month intervals corresponding to dry/rainy seasons over one year (2016–2017). Household-surveys assessed the social reception of the intervention. Houses with ITS were 79–85% less infested with Aedes females than control houses up to one-year PI. A similar significant trend was observed for blood-fed Ae. aegypti females (76–82%). Houses with ITS had significantly less infected female Ae. aegypti than controls during the peak of the epidemic (OR = 0.15, 95%CI: 0.08–0.29), an effect that was significant up to a year PI (OR = 0.24, 0.15–0.39). Communities strongly accepted the intervention, due to its perceived mode of action, the prevalent risk for Aedes-borne diseases in the area, and the positive feedback from neighbours receiving ITS.

Conclusions/Significance

We show evidence of the protective efficacy of ITS against an arboviral disease of major relevance, and discuss the relevance of our findings for intervention adoption.
Space-time risk cluster of visceral leishmaniasis in Brazilian endemic region with high social vulnerability: An ecological time series study
Authors: Ribeiro Caique J. N. , dos Santos Allan D. , Lima Shirley V. M. A. , da Silva Eliete R. , Ribeiro Bianca V. S. , Duque Andrezza M. , Peixoto Marcus V. S. , dos Santos Priscila L. , de Oliveira Iris M. , Lipscomb Michael W. , de Araújo Karina C. G. M. , de Moura Tatiana R.
Published: January 2021

Background

Despite visceral leishmaniasis (VL) being epidemic in most Brazilian regions, the Northeast region is responsible for the highest morbidity and mortality outcomes within the country.

Objective

To analyse the spatiotemporal dynamics of VL cases to identify the temporal trends and high-risk areas for VL transmission, as well as the association of the disease with social vulnerability in Brazilian Northeast.

Methods

We carried out an ecological time series study employing spatial analysis techniques using all VL confirmed cases of 1,794 municipalities of Brazilian Northeast between the years 2000 to 2017. The Social Vulnerability Index (SVI) was used to represent the social vulnerability. Incidence rates were standardized and smoothed by the Local Empirical Bayesian Method. Time trends were examined through segmented linear regression. Spatiotemporal analysis consisted of uni- and bivariate Global and Local Moran indexes and space-time scan statistics.

Results

Incidence rate remained stable and ranged from 4.84 to 3.52 cases/100,000 inhabitants. There was higher case prevalence between males (62.71%), children and adolescents (63.27%), non-white (69.75%) and urban residents (62.58%). Increasing trends of new cases were observed among adult male subjects (≥ 40 years old) and urban residents. Importantly, VL incidence showed a direct spatial dependence. Spatial and space-time clusters were identified insertãoandmeio-nortesub-regions, overlapping with high social vulnerability areas.

Conclusions

VL is a persistent health issue in Brazilian Northeast and associated with social vulnerability. Space-time clustering of VL cases in socially vulnerable municipalities demands intersectoral public policies of surveillance and control, with focus on reducing inequalities and improving living conditions for regional inhabitants.
S. mansoni SmKI-1 Kunitz-domain: Leucine point mutation at P1 site generates enhanced neutrophil elastase inhibitory activity
Authors: Mambelli Fábio , Santos Bruno P. O. , Morais Suellen B. , Gimenez Enrico G. T. , Astoni Duana C. dos S. , Braga Amanda D. , Ferreira Rafaela S. , Amaral Flávio A. , de Magalhães Mariana T. Q. , C. Oliveira Sergio
Published: January 2021

TheSchistosoma mansoni SmKI-1 protein is composed of two domains: a Kunitz-type serine protease inhibitor motif (KD) and a C-terminus domain with no similarity outside the genera. Our previous work has demonstrated that KD plays an essential role in neutrophil elastase (NE) binding blockage, in neutrophil influx and as a potential anti-inflammatory molecule. In order to enhance NE blocking capacity, we analyzed the KD sequence from a structure-function point of view and designed specific point mutations in order to enhance NE affinity. We substituted the P1 site residue at the reactive site for a leucine (termed RL-KD), given its central role for KD’s inhibition to NE. We have also substituted a glutamic acid that strongly interacts with the P1 residue for an alanine, to help KD to be buried on NE S1 site (termed EA-KD). KD and the mutant proteins were evaluatedin silicoby molecular docking to human NE, expressed inEscherichia coliand tested towards its NE inhibitory activity. Both mutated proteins presented enhanced NE inhibitory activityin vitroand RL-KD presented the best performance. We further tested RL-KDin vivoin an experimental model of monosodium urate (MSU)-induced acute arthritis. RL-KD showed reduced numbers of total cells and neutrophils in the mouse knee cavity when compared to KD. Nevertheless, both RL-KD and KD reduced mice hypernociception in a similar fashion. In summary, our results demonstrated that both mutated proteins showed enhanced NE inhibitory activityin vitro. However, RL-KD had a prominent effect in diminishing inflammatory parametersin vivo.
Assessment on the effectiveness of vessel-approach regulations to protect cetaceans in Australia: A review on behavioral impacts with case study on the threatened Burrunan dolphin (Tursiops australis)
Authors: Puszka Helena , Shimeta Jeff , Robb Kate
Published: January 2021

Vessels cause considerable disturbance to cetaceans world-wide, with potential long-term impacts to population viability. Here we present a comprehensive review of vessel impacts to cetacean behavior in Australian waters (2003–2015), finding inadequate protections to be in place. The majority of these studies found trends of decreased animal travel and resting behavioral states as well as low compliance to regulations, and they recommended further regulatory action such as greater enforcement or monitoring, or passive management strategies. As a case study, we conducted the first field assessment of vessel compliance with theWildlife (Marine Mammal) Regulations 2009in Gippsland Lakes, Australia, and provide the first assessment of the endangered Gippsland Lakes Burrunan dolphin (Tursiops australis) population’s behavioral ecology. Dolphin behavior and vessel regulation compliance data were collected during boat-based surveys of Gippsland Lakes from July 2017 to January 2018, with a total of 22 dolphin group sightings resulting in 477 five-minute point samples. 77% of dolphin sightings involved vessel interactions (within 400 m), and 56 regulation breaches were observed. These breaches were most severe in summer (mean = 4.54 breaches/hour). Vessels were found to alter dolphin behavior before, during, and after interactions and regulation breaches, including increased mating (mate guarding) and milling behavioral states, and increased ‘fish catch’, ‘high leap’ and ‘tail slap’ behavioral events. These behavioral changes may indicate masking of the dolphins' acoustic communication, disturbance of prey, increased dolphin transition behaviors, and/or induced stress and changes to group structure (including increased mate guarding). While our results provide evidence of short-term altered behavior, the potential for long-term effects on population dynamics for this threatened species is high. In the context of reported inadequate cetacean protection Australia-wide, our management recommendations include greater monitoring and enforcement, and the utilisation of adaptive management.
Measuring office workplace interactions and hand hygiene behaviors through electronic sensors: A feasibility study
Authors: Zivich Paul N. , Huang Will , Walsh Ali , Dutta Prabal , Eisenberg Marisa , Aiello Allison E.
Published: January 2021

Office-based workplaces are an important but understudied context for infectious disease transmission. We examined the feasibility of two different sensors (Opos and Bluetooth beacons) for collecting person-to-person contacts and hand hygiene in office-based workplaces. Opo is an interaction sensor that captures sensor-to-sensor interactions through ultrasonic frequencies, which correspond to face-to-face contacts between study participants. Opos were additionally used to measure hand hygiene events by affixing sensors to soap and alcohol-based hand sanitizer dispensers. Bluetooth beacons were used in conjunction with a smartphone application and recorded proximity contacts between study participants. Participants in two office sites were followed for one-week in their workplace in March 2018. Contact patterns varied by time of day and day of the week. Face-to-face contacts were of shorter mean duration than proximity contacts. Supervisors had fewer proximity contacts but more face-to-face contacts than non-supervisors. Self-reported hand hygiene was substantively higher than sensor-collected hand hygiene events and duration of hand washing events was short (median: 9 seconds, range: 2.5–33 seconds). Given that office settings are key environments in which working age populations spend a large proportion of their time and interactions, a better characterization of empirical social networks and hand hygiene behaviors for workplace interactions are needed to mitigate outbreaks and prepare for pandemics. Our study demonstrates that implementing sensor technologies for tracking interactions and behaviors in offices is feasible and can provide new insights into real-world social networks and hygiene practices. We identified key social interactions, variability in hand hygiene, and differences in interactions by workplace roles. High-resolution network data will be essential for identifying the most effective ways to mitigate infectious disease transmission and develop pandemic preparedness plans for the workplace setting.
“I wish to remain HIV negative”: Pre-exposure prophylaxis adherence and persistence in transgender women and men who have sex with men in coastal Kenya
Authors: Kimani Makobu , van der Elst Elise M. , Chirro Oscar , Wahome Elizabeth , Ibrahim Fauz , Mukuria Nana , de Wit Tobias F. Rinke , Graham Susan M. , Operario Don , Sanders Eduard J.
Published: January 2021

Background

Transgender women (TGW) and men who have sex with men (MSM) in sub-Saharan Africa have high HIV acquisition risks and can benefit from daily pre-exposure prophylaxis (PrEP). We assessed PrEP adherence by measuring tenofovir-diphosphate (TFV-DP) levels and explore motives for PrEP persistence in TGW and MSM.

Methods

Participants were enrolled in a one-year PrEP programme and made quarterly visits irrespective of whether they were still using PrEP. At their month 6 visit, participants provided a dried blood spot to test for TFV-DP levels; protective levels were defined as those compatible with ≥4 pills per week (700–1249 fmol/punch). Before TFV-DP levels were available, a sub-set of these participants were invited for an in-depth interview (IDI). Semi-structured IDI topic guides were used to explore motives to uptake, adhere to, and discontinue PrEP. IDI data were analyzed thematically.

Results

Fifty-three participants (42 MSM and 11 TGW) were enrolled. At month 6, 11 (20.7%) participants (8 MSM and 3 TGW) were lost to follow up or stopped taking PrEP. Any TFV-DP was detected in 62.5% (5/8) of TGW vs. 14.7% of MSM (5/34, p = 0.01). Protective levels were detected in 37.5% of TGW (3/8), but not in any MSM. Nineteen IDI were conducted with 7 TGW and 9 MSM on PrEP, and 1 TGW and 2 MSM off PrEP. Unplanned or frequent risky sexual risk behaviour were the main motives for PrEP uptake. Among participants on PrEP, TGW had a more complete understanding of the benefits of PrEP. Inconsistent PrEP use was attributed to situational factors. Motives to discontinue PrEP included negative reactions from partners and stigmatizing healthcare services.

Conclusion

While MSM evinced greater adherence challenges in this PrEP programme, almost 40% of TGW were protected by PrEP. Given high HIV incidences in TGW these findings hold promise for TGW PrEP programming in the region.
Feasibility and validation of a web-based platform for the self-administered patient collection of demographics, health status, anxiety, depression, and cognition in community dwelling elderly
Authors: Calamia Matthew , Weitzner Daniel S. , De Vito Alyssa N. , Bernstein John P. K. , Allen Ray , Keller Jeffrey N.
Published: January 2021

The coronavirus disease pandemic has brought a new urgency for the development and deployment of web-based applications which complement, and offer alternatives to, traditional one-on-one consultations and pencil-and-paper (PaP) based assessments that currently dominate clinical research. We have recently developed a web-based application that can be used for the self-administered collection of patient demographics, self-rated health, depression and anxiety, and cognition as part of a single platform. In this study we report the findings from a study with 155 cognitively healthy older adults who received established PaP versions, as well as our novel computerized measures of self-rated health, depression and anxiety, and cognition. Moderate to high correlations were observed between PaP and web- based measures of self-rated health (r = 0.77), depression and anxiety (r = 0.72), and preclinical Alzheimer’s disease cognitive composite (PACC) (r = .61). Test-retest correlations were variable with high correlations for a measure of processing speed and a measure of delayed episodic memory. Taken together, these data support the feasibility and validity of utilization of this novel web-based platform as a new alternative for collecting patient demographics and the assessment of self-rated health, depression and anxiety, and cognition in the elderly.
Beyond sensory conflict: The role of beliefs and perception in motion sickness
Authors: Nooij Suzanne A. E. , Bockisch Christopher J. , Bülthoff Heinrich H. , Straumann Dominik
Published: January 2021

Illusory self-motion often provokes motion sickness, which is commonly explained in terms of an inter-sensory conflict that is not in accordance with previous experience. Here we address the influence of cognition in motion sickness and show that such a conflict isnotprovocative when the observer believes that the motion illusion is indeed actually occurring. Illusory self-motion and motion sickness were elicited in healthy human participants who were seated on a stationary rotary chair inside a rotating optokinetic drum. Participants knew that both chair and drum could rotate but were unaware of the actual motion stimulus. Results showed that motion sickness was correlated with the discrepancy between participants’perceivedself-motion and participants’beliefsabout the actual motion. Together with the general motion sickness susceptibility, this discrepancy accounted for 51% of the variance in motion sickness intensity. This finding sheds a new light on the causes of visually induced motion sickness and suggests that it is not governed by an inter-sensory conflict per se, but by beliefs concerning the actual self-motion. This cognitive influence provides a promising tool for the development of new countermeasures.
A longitudinal study of plasma BAFF levels in mothers and their infants in Uganda, and correlations with subsets of B cells
Authors: Rönnberg Caroline , Lugaajju Allan , Nyman Anna , Hammar Ulf , Bottai Matteo , Lautenbach Maximilian Julius , Sundling Christopher , Kironde Fred , Persson Kristina E. M.
Published: January 2021

Malaria is a potentially life-threatening disease with approximately half of the world’s population at risk. Young children and pregnant women are hit hardest by the disease. B cells and antibodies are part of an adaptive immune response protecting individuals continuously exposed to the parasite. An infection with Plasmodium falciparum can cause dysregulation of B cell homeostasis, while antibodies are known to be key in controlling symptoms and parasitemia. BAFF is an instrumental cytokine for the development and maintenance of B cells. Pregnancy alters the immune status and renders previously clinically immune women at risk of severe malaria, potentially due to altered B cell responses associated with changes in BAFF levels. In this prospective study, we investigated the levels of BAFF in a malaria-endemic area in mothers and their infants from birth up to 9 months. We found that BAFF-levels are significantly higher in infants than in mothers. BAFF is highest in cord blood and then drops rapidly, but remains significantly higher in infants compared to mothers even at 9 months of age. We further correlated BAFF levels to P. falciparum-specific antibody levels and B cell frequencies and found a negative correlation between BAFF and both P. falciparum-specific and total proportions of IgG+ memory B cells, as well as CD27− memory B cells, indicating that exposure to both malaria and other diseases affect the development of B-cell memory and that BAFF plays a part in this. In conclusion, we have provided new information on how natural immunity against malaria is formed.
Value of endoscopic ultrasonography in the observation of the remnant pancreas after pancreatectomy
Authors: Maruyama Hirotsugu , Hanada Keiji , Shimizu Akinori , Minami Tomoyuki , Hirano Naomiti , Hino Fumiaki , Abe Tomoyuki , Amano Hironobu , Fujiwara Yasuhiro
Published: January 2021

Background

Endoscopic ultrasonography (EUS) is proven to be a more specific and sensitive method for detecting pancreatic lesions. However, usefulness of EUS after pancreatectomy has not been reported. This study aimed to evaluate the observational capability of EUS for the remnant pancreas (RP) after pancreatectomy.

Patient and methods

This single-center, retrospective study enrolled 395 patients who underwent pancreatectomy at Onomichi General Hospital between December 2002 and March 2016, 45 patients who underwent EUS for RP were included for analysis. We evaluated the usefulness of EUS for RP using logistic regression analysis.

Results

Complete observation of the RP was done in 42 patients (93%). In the initial surgical procedure, 21 patients underwent pancreaticoduodenectomy (PD), and 24 patients underwent distal pancreatectomy (DP). PD and DP were observed in 85% (18/21) and 100% (24/24) cases, respectively. A comparison of the detection capability of EUS and contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) showed that EUS was significantly superior to contrast-enhanced CT or MRI (p < 0.01). Eight of the 45 patients showed recurrence lesions in the RP. The median recurrence period was 33 months. Predictive factors for recurrence in the univariate and multivariate analyses were significantly different in space occupying lesion with EUS findings (p < 0.01) and elevated CA19-9(p < 0.01).

Conclusions

EUS was able to observe the RP in almost all cases. In addition, the detection capability of EUS was significantly superior to those of CT or MRI. We recommend that all patients with RP should undergo EUS, and a longer follow-up must be performed.
Cannabis sativa subsp. sativa’s pharmacological properties and health effects: A scoping review of current evidence
Authors: Lim Xin Yi , Tan Terence Yew Chin , Muhd Rosli Siti Hajar , Sa’at Muhammad Nor Farhan , Sirdar Ali Syazwani , Syed Mohamed Ami Fazlin
Published: January 2021

Introduction

Hemp (Cannabis sativasubsp.sativa), commonly used for industrial purposes, is now being consumed by the public for various health promoting effects. As popularity of hemp research and claims of beneficial effects rises, a systematic collection of current scientific evidence on hemp’s health effects and pharmacological properties is needed to guide future research, clinical, and policy decision making.

Objective

To provide an overview and identify the present landscape of hemp research topics, trends, and gaps.

Methods

A systematic search and analysis strategy according to the preferred reporting items for systematic review and meta-analysis-ScR (PRISMA-ScR) checklist on electronic databases including MEDLINE, OVID (OVFT, APC Journal Club, EBM Reviews), Cochrane Library Central and Clinicaltrials.gov was conducted to include and analyse hemp research articles from 2009 to 2019.

Results

65 primary articles (18 clinical, 47 pre-clinical) were reviewed. Several randomised controlled trials showed hempseed pills (in Traditional Chinese Medicine formulation MaZiRenWan) improving spontaneous bowel movement in functional constipation. There was also evidence suggesting benefits in cannabis dependence, epilepsy, and anxiety disorders. Pre-clinically, hemp derivatives showed potential anti-oxidative, anti-hypertensive, anti-inflammatory, anti-diabetic, anti-neuroinflammatory, anti-arthritic, anti-acne, and anti-microbial activities. Renal protective effects and estrogenic properties were also exhibitedin vitro.

Conclusion

Current evidence on hemp-specific interventions are still preliminary, with limited high quality clinical evidence for any specific therapeutic indication. This is mainly due to the wide variation in test item formulation, as the multiple variants of this plant differ in their phytochemical and bioactive compounds. Future empirical research should focus on standardising the hemp plant for pharmaceutical use, and uniformity in experimental designs to strengthen the premise of using hemp in medicine.
Balancing time use for children’s fitness and adiposity: Evidence to inform 24-hour guidelines for sleep, sedentary time and physical activity
Authors: Dumuid Dorothea , Wake Melissa , Burgner David , Tremblay Mark S. , Okely Anthony D. , Edwards Ben , Dwyer Terence , Olds Timothy
Published: January 2021

Purpose

Daily time spent on one activity cannot change without compensatory changes in others, which themselves may impact on health outcomes. Optimal daily activity combinations may differ across outcomes. We estimated optimal daily activity durations for the highest fitness and lowest adiposity.

Methods

Cross-sectional Child Health CheckPoint data (1182 11-12-year-olds; 51% boys) from the population-based Longitudinal Study of Australian Children were used. Daily activity composition (sleep, sedentary time, light physical activity [LPA], moderate-to-vigorous physical activity [MVPA]) was from 8-day, 24-hour accelerometry. We created composite outcomes for fitness (VO2max; standing long jump) and adiposity (waist-to-height ratio; body mass index; fat-to-fat-free log-ratio). Adjusted compositional models regressed activity log-ratios against each outcome. Best activity compositions (optimal time-use zones) were plotted in quaternary tetrahedrons; the overall optimal time-use composition was the center of the overlapping area.

Results

Time-use composition was associated with fitness and adiposity (all measures p<0.001). Optimal time use differed for fitness and adiposity. While both maximized MVPA and minimized sedentary time, optimal fitness days had higher LPA (3.4 h) and shorter sleep (8.25 h), but optimal adiposity days had lower LPA (1.0 h) and longer sleep (10.9 h). Balancing both outcomes, the overall optimal time-use composition was (mean [range]): 10.2 [9.5; 10.5] h sleep, 9.9 [8.8; 11.2] h sedentary time, 2.4 [1.8; 3.2] h LPA and 1.5 [1.5; 1.5] h MVPA.

Conclusion

Optimal time use for children’s fitness and adiposity involves trade-offs. To best balance both outcomes, estimated activity durations for sleep and LPA align with, but for MVPA exceed, 24-h guidelines.
Exploring people’s thoughts about the causes of ethnic stereotypes
Authors: Schmalor Anita , Cheung Benjamin Y. , Heine Steven J.
Published: January 2021

Much research has shown that people tend to view genes in rather deterministic ways—often termed genetic essentialism. We explored how people would view the causes of ethnic stereotypes in contexts where human genetic variability was either emphasized or downplayed. In two studies with over 1600 participants we found that people viewed ethnic stereotypes to be more of a function of underlying genetics after they read an article describing how ancestry can be estimated by geographic distributions of gene frequencies than after reading an article describing how relatively homogeneous the human genome was or after reading a control essay. Moreover, people were more likely to attribute ethnic stereotypes to genes when they scored higher on a measure of genetic essentialism or when they had less knowledge about genes. Our understanding of stereotypes is a function of our understanding of genetics.
A versatile cryo-transfer system, connecting cryogenic focused ion beam sample preparation to atom probe microscopy
Authors: Macauley Chandra , Heller Martina , Rausch Alexander , Kümmel Frank , Felfer Peter
Published: January 2021

Atom probe tomography (APT) is a powerful technique to obtain 3D chemical and structural information, however the ‘standard’ atom probe experimental workflow involves transfer of specimens at ambient conditions. The ability to transfer air- or thermally-sensitive samples between instruments while maintaining environmental control is critical to prevent chemical or morphological changes prior to analysis for a variety of interesting sample materials. In this article, we describe a versatile transfer system that enables cryogenic- or room-temperature transfer of specimens in vacuum or atmospheric conditions between sample preparation stations, a focused ion beam system (Zeiss Crossbeam 540) and a widely used commercial atom probe system (CAMECA LEAP 4000X HR). As an example for the use of this transfer system, we present atom probe data of gallium- (Ga)-free grain boundaries in an aluminum (Al) alloy specimen prepared with a Ga-based FIB.
Chronic kidney disease and the outcomes of fibrinolysis for ST-segment elevation myocardial infarction: A real-world study
Authors: Xie Wuxiang , Patel Anushka , Boersma Eric , Feng Lin , Li Min , Gao Runlin , Wu Yangfeng
Published: January 2021

Background

In low-resource regions, fibrinolytic therapy is often the only option for ST-elevation myocardial infarction (STEMI) patients as primary percutaneous coronary intervention (PCI) is often not available and patients are hardly transferred to a medical center with PCI capacity within the first 120 minutes. Chronic kidney disease (CKD) is one of the most frequently encountered complications of STEMI. However, the evidence for the efficacy of fibrinolytic therapy in STEMI patients with CKD is still limited. The aim of this study is to test whether CKD modifies the association between fibrinolytic therapy and short-term major adverse cardiovascular events (MACEs) among patients with STEMI.

Methods and findings

This is a real-world study analyzing the data from 9508 STEMI patients (mean age: 64.0±12.4 years; male: 70.1%) in the third phase of Clinical Pathways in Acute Coronary Syndromes program (CPACS-3), which is a large study of the management of acute coronary syndromes (ACS) in 101 county hospitals without PCI capacity in China. CKD was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1·73 m2 at the admission. The primary outcome is short-term MACEs, including all-cause death, recurrent myocardial infarction, or nonfatal stroke. Patients were recruited consecutively between October 2011 and November 2014. Out of them, 1282 patients (13.5%) were classified as having CKD. Compared with non-CKD patients, CKD patients were less likely to receive fibrinolytic therapy than non-CKD patients (26.4% vs. 38.9%, P<0.001), more likely to experience a failed fibrinolytic therapy (32.8% vs. 16.9%), and had a higher risk of short-term MACEs (19.7% vs. 5.6%). After full adjustment, use of fibrinolytic therapy was associated with a significantly lower risk of short-term MACEs in non-CKD patients (relative risk [RR] = 0.87, 95% confidence interval [CI]: 0.76–0.99), but not in CKD patients (P for interaction = 0.026). Further analysis stratified by the success of fibrinolysis showed that compared with patients who did not receive fibrinolytic therapy, patients with successful fibrinolysis had a lower risk of short-term MACEs that was similar between patients with (RR = 0.71, 95% CI: 0.55–0.82) and without CKD (RR = 0.67, 95% CI: 0.55–0.92), while patients with unsuccessful fibrinolysis had a similarly higher risk in CKD patients (RR = 1.25, 95% CI: 1.09–1.43) and non-CKD patients (RR = 1.30, 95% CI: 1.13–1.50).

Conclusions

CKD reduced the likelihood of successful fibrinolysis and increased the risk of short-term MACEs in patients with STEMI. Attention should be paid to how to improve the success rate of fibrinolytic therapy for STEMI patients with CKD.

Trial registration

The CPACS-3 study was registered on www.clinicaltrials.gov (NCT01398228).
Space-time smoothing of mortality estimates in children aged 5-14 in Sub-Saharan Africa
Authors: Schlüter Benjamin-Samuel , Masquelier Bruno
Published: January 2021

To meet the SDG requirement of spatial disaggregation of indicators, several methods have been developed to generate estimates of under-five mortality at the sub-national level. The reliability of sub-national mortality estimates in children aged 5-14 with the available survey data has not been evaluated so far. We generate Admin-1 sub-national estimates of the risk of dying in children aged less than five (5q0) and those aged 5 to 14 years old (10q5). We use 96 Demographic and Health Surveys (DHS) in 20 Sub-Saharan countries having at least 3 surveys designed to be representative at a sub-national level. The estimates account for the complex sample design of DHS and HIV-related biases in young children. A Bayesian space-time model previously developed for under-five mortality is used to smooth estimates across space and time in both age groups to reduce problems associated with data sparsity. The posterior distributions of the probability10q5are used to compute coefficients of variation and assess precision. Sufficiently precise estimates are retained to study the sub-national relationship between age-specific mortality rates (5q0and10q5), accounting for uncertainty in sub-national levels. Out of 1,132 space-time estimates, 62.3% are considered sufficiently precise with high heterogeneity across countries. Across all periods, sub-national estimates of mortality in children aged 0-4 are highly correlated with those in older children and young adolescents but this correlation is largely driven by the mortality decline. Within specific periods of time, it is often impossible to assess the relationship between mortality rates in the two age groups at the sub-national level, except in Nigeria, Ethiopia, Cameroon, Senegal and Zambia. As increased attention is devoted to survival after age 5, more research is needed to ensure that sub-national areas with specific interventions required for older children can be correctly identified.
Bmi-1 regulates mucin levels and mucin O-glycosylation in the submandibular gland of mice
Authors: Kameyama Akihiko , Nishijima Risa , Yamakoshi Kimi
Published: January 2021

Mucins, the major components of salivary mucus, are large glycoproteins abundantly modified with O-glycans. Mucins present on the surface of oral tissues contribute greatly to the maintenance of oral hygiene by selectively adhering to the surfaces of microbes via mucin O-glycans. However, due to the complex physicochemical properties of mucins, there have been relatively few detailed analyses of the mechanisms controlling the expression of mucin genes and the glycosyltransferase genes involved in glycosylation. Analysis performed using supported molecular matrix electrophoresis, a methodology developed for mucin analysis, and knockout mice without the polycomb group protein Bmi-1 revealed that Bmi-1 regulates mucin levels in the submandibular gland by suppressing the expression of the mucin Smgc gene, and that Bmi-1 also regulates mucin O-glycosylation via suppression of the glycosyltransferase Gcnt3 gene in the submandibular gland.
Exploring the participation of young citizen scientists in scientific research: The case of iNaturalist
Authors: Aristeidou Maria , Herodotou Christothea , Ballard Heidi L. , Young Alison N. , Miller Annie E. , Higgins Lila , Johnson Rebecca F.
Published: January 2021

Online citizen science projects have broadened options for accessing science and enabled different forms of participation in scientific research for adult and young volunteers. Yet, little is known regarding participation patterns among youth participants. Quantitative approaches were used to investigate the contribution of 183 young volunteers to citizen science on the iNaturalist platform and the participation behaviour that relates to their contribution. The participants accessed and used iNaturalist as part of one-day field-based events (bioblitzes) facilitated by museums. Compared to the observation behaviour of all iNaturalist users, as documented on the platform, the young volunteers observe fewer plants and birds, and more molluscs, arachnids and insects. The average daily contributions of young volunteers were found to be positively associated with a large proportion of active days on iNaturalist and a systematic contribution behaviour, yet negatively related to a long duration on the platform. This study enhances our understanding of young volunteers’ contributions to citizen science and provides insights for research on participation in online citizen science. Our findings have implications on how museums design the field-based events to encourage follow-up systematic participation and maintain active contribution.
Systematic identification of autophagy-related proteins in Aedes albopictus
Authors: Wang Yu , Qiao Jialu , Zhang Dandan , Zhong Chunyan , Wang Shengya , Li Xiaomei , Feng Lingyan , Shi Shen , Wang Bingxue , Liu Qingzhen
Published: January 2021

Autophagy is a conserved cellular process playing a role in maintenance of cellular homeostasis and response to changing nutrient conditions via degradation and recirculation of cellular redundant components. Autophagy-related proteins (Atg) play important function in autophagy pathway. Aedes albopictus mosquito is an effective vector transmitting multiple viruses which cause serious human diseases. Moreover, Aedes albopictus mosquito is becoming a serious threat to human health due to its widening distribution in recent years and thus worth of more research attention. It was reported that autophagy might play a role in viral infection in Aedes mosquito. To better understand the interaction between autophagy and arbovirus infection in mosquito system, it is necessary to identify autophagy pathway in the system. However, autophagy in Aedes albopictus mosquito is still poorly understood so far. We recently identified AaAtg8, the first Atg protein reported in Aedes albopictus mosquito. This work further identified twelve atg genes in Aedes albopictus mosquito. Sequence and phylogenetic analysis of the twelve atg genes were performed. Expression profiles of all the twelve Aaatg genes in different developmental stages and genders of Aedes albopictus mosquito were conducted. Effects of chemicals inhibiting or inducing autophagy on the levels of eight identified AaAtg proteins were examined. The function of two identified AaAtg proteins AaAtg6 and AaAtg16 and their response to arbovirus SINV infection were studied preliminarily. Taken together, this work systematically identified Aedes albopictus atg genes and provided basic information which might help to elucidate the autophagy pathway and the role of autophagy in arbovirus infection in Aedes mosquito system.
T-bet-dependent ILC1- and NK cell-derived IFN-γ mediates cDC1-dependent host resistance against Toxoplasma gondii
Authors: López-Yglesias Américo H. , Burger Elise , Camanzo Ellie , Martin Andrew T. , Araujo Alessandra M. , Kwok Samantha F. , Yarovinsky Felix
Published: January 2021

Host resistance against intracellular pathogens requires a rapid IFN-γ mediated immune response. We reveal that T-bet-dependent production of IFN-γ is essential for the maintenance of inflammatory DCs at the site of infection with a common protozoan parasite,Toxoplasma gondii. A detailed analysis of the cellular sources for T-bet-dependent IFN-γ identified that ILC1s and to a lesser degree NK, but not TH1 cells, were involved in the regulation of inflammatory DCs via IFN-γ. Mechanistically, we established that T-bet dependent innate IFN-γ is critical for the induction of IRF8, an essential transcription factor for cDC1s. Failure to upregulate IRF8 in DCs resulted in acute susceptibility toT.gondiiinfection. Our data identifies that T-bet dependent production of IFN-γ by ILC1 and NK cells is indispensable for host resistance against intracellular infection via maintaining IRF8+ inflammatory DCs at the site of infection.
Immunological design of commensal communities to treat intestinal infection and inflammation
Authors: Brown Rebecca L. , Larkinson Max L. Y. , Clarke Thomas B.
Published: January 2021

The immunological impact of individual commensal species within the microbiota is poorly understood limiting the use of commensals to treat disease. Here, we systematically profile the immunological fingerprint of commensals from the major phyla in the human intestine (Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria) to reveal taxonomic patterns in immune activation and use this information to rationally design commensal communities to enhance antibacterial defenses and combat intestinal inflammation. We reveal that Bacteroidetes and Firmicutes have distinct effects on intestinal immunity by differentially inducing primary and secondary response genes. Within these phyla, the immunostimulatory capacity of commensals from the Bacteroidia class (Bacteroidetes phyla) reflects their robustness of TLR4 activation and Bacteroidia communities rely solely on this receptor for their effects on intestinal immunity. By contrast, within the Clostridia class (Firmicutes phyla) it reflects the degree of TLR2 and TLR4 activation, and communities of Clostridia signal via both of these receptors to exert their effects on intestinal immunity. By analyzing the receptors, intracellular signaling components and transcription factors that are engaged by different commensal species, we identify canonical NF-κB signaling as a critical rheostat which grades the degree of immune stimulation commensals elicit. Guided by this immunological analysis, we constructed a cross-phylum consortium of commensals (Bacteroides uniformis,Bacteroides ovatus,Peptostreptococcus anaerobiusandClostridium histolyticum) which enhances innate TLR, IL6 and macrophages-dependent defenses against intestinal colonization by vancomycin resistant Enterococci, and fortifies mucosal barrier function during pathological intestinal inflammation through the same pathway. Critically, the setpoint of intestinal immunity established by this consortium is calibrated by canonical NF-κB signaling. Thus, by profiling the immunological impact of major human commensal species our work paves the way for rational microbiota reengineering to protect against antibiotic resistant infections and to treat intestinal inflammation.
Dissecting genetic and sex-specific sources of host heterogeneity in pathogen shedding and spread
Authors: Siva-Jothy Jonathon A. , Vale Pedro F.
Published: January 2021

Host heterogeneity in disease transmission is widespread but precisely how different host traits drive this heterogeneity remains poorly understood. Part of the difficulty in linking individual variation to population-scale outcomes is that individual hosts can differ on multiple behavioral, physiological and immunological axes, which will together impact their transmission potential. Moreover, we lack well-characterized, empirical systems that enable the quantification of individual variation in key host traits, while also characterizing genetic or sex-based sources of such variation. Here we usedDrosophila melanogasterand Drosophila C Virus as a host-pathogen model system to dissect the genetic and sex-specific sources of variation in multiple host traits that are central to pathogen transmission. Our findings show complex interactions between genetic background, sex, and female mating status accounting for a substantial proportion of variance in lifespan following infection, viral load, virus shedding, and viral load at death. Two notable findings include the interaction between genetic background and sex accounting for nearly 20% of the variance in viral load, and genetic background alone accounting for ~10% of the variance in viral shedding and in lifespan following infection. To understand how variation in these traits could generate heterogeneity in individual pathogen transmission potential, we combined measures of lifespan following infection, virus shedding, and previously published data on fly social aggregation. We found that the interaction between genetic background and sex explained ~12% of the variance in individual transmission potential. Our results highlight the importance of characterising the sources of variation in multiple host traits to understand the drivers of heterogeneity in disease transmission.
Naturally occurring substitution in one amino acid in VHSV phosphoprotein enhances viral virulence in flounder
Authors: Hwang Jee Youn , Lee Unn Hwa , Heo Min Jin , Kim Min Sun , Jeong Ji Min , Kim So Yeon , Kwon Mun Gyeong , Jee Bo Young , Kim Ki Hong , Park Chan-Il , Park Jeong Woo
Published: January 2021

Viral hemorrhagic septicemia virus (VHSV) is a rhabdovirus that causes high mortality in cultured flounder. Naturally occurring VHSV strains vary greatly in virulence. Until now, little has been known about genetic alterations that affect the virulence of VHSV in flounder. We recently reported the full-genome sequences of 18 VHSV strains. In this study, we determined the virulence of these 18 VHSV strains in flounder and then the assessed relationships between differences in the amino acid sequences of the 18 VHSV strains and their virulence to flounder. We identified one amino acid substitution in the phosphoprotein (P) (Pro55-to-Leu substitution in the P protein; PP55L) that is specific to highly virulent strains. This PP55L substitution was maintained stably after 30 cell passages. To investigate the effects of the PP55L substitution on VHSV virulence in flounder, we generated a recombinant VHSV carrying PP55L (rVHSV-P) from rVHSV carrying P55 in the P protein (rVHSV-wild). The rVHSV-P produced high level of viral RNA in cells and showed increased growth in cultured cells and virulence in flounder compared to the rVHSV-wild. In addition, rVHSV-P significantly inhibited the induction of the IFN1 gene in both cells and fish at 6 h post-infection. An RNA-seq analysis confirmed that rVHSV-P infection blocked the induction of several IFN-related genes in virus-infected cells at 6 h post-infection compared to rVHSV-wild. Ectopic expression of PP55L protein resulted in a decrease in IFN induction and an increase in viral RNA synthesis in rVHSV-wild-infected cells. Taken together, our results are the first to identify that the P55L substitution in the P protein enhances VHSV virulence in flounder. The data from this study add to the knowledge of VHSV virulence in flounder and could benefit VHSV surveillance efforts and the generation of a VHSV vaccine.