bluuebunny/crossref_metadata_2025 huggingface dataset:
miR-335-5p suppresses gastric cancer progression by targeting MAPK10
Authors: Gao Yi , Wang Yanfeng , Wang Xiaofei , Zhao Changan , Wang Fenghui , Du Juan , Zhang Huahua , Shi Haiyan , Feng Yun , Li Dan , Yan Jing , Yao Yan , Hu Weihong , Ding Ruxin , Zhang Mengjie , Wang Lumin , Huang Chen , Zhang Jing
Published: January 2021

Background

Recent studies have established the roles of microRNAs (miRNAs) in cancer progression. The aberrant expression of miR-335-5p has been reported in many cancers, including gastric cancer (GC). In this study, the precise roles of miR-335-5p in GC as well as the molecular mechanisms underlying its effects, including the role of its target MAPK10, were evaluated.

Methods

Quantitative real-time PCR was used to evaluate miR-335-5p levels in GC cell lines and tissues. MTT and colony formation assays were used to detect cell proliferation, and Transwell and wound-healing assays were used to evaluate the invasion and migration of GC cells. The correlation between levels of miR-335-5p and the cell cycle-related target gene mitogen-activated protein kinase 10 (MAPK10) in GC was analyzed. In addition, the candidate target was evaluated by a luciferase reporter assay, qRT-PCR, and western blotting.

Results

The levels of miR-335-5p were downregulated in GC tissues and cell lines. Furthermore, miR-335-5p inhibited the proliferation and migration of GC cells and induced apoptosis. Additionally, miR-335-5p arrested the cell cycle at the G1/S phase in GC cells in vitro. Levels of miR-335-5p and the cell cycle-related target gene MAPK10 in GC were correlated, and MAPK10 was directly targeted by miR-335-5p.

Conclusions

These data suggest that miR-335-5p is a tumor suppressor and acts via MAPK10 to inhibit GC progression.
Three novel circRNAs upregulated in tissue and plasma from hepatocellular carcinoma patients and their regulatory network
Authors: Wang Lianghai , Zhou Lisha , Hou Jun , Meng Jin , Lin Ke , Wu Xiangwei , Chen Xueling
Published: January 2021

Background

The regulatory roles of circular RNAs (circRNAs) in tumorigenesis have attracted increasing attention. However, novel circRNAs with the potential to be used as serum/plasma biomarkers and their regulatory mechanism in the pathogenesis of hepatocellular carcinoma (HCC) remain explored.

Methods

CircRNA expression profiles of tumor tissues and plasma samples from HCC patients were compiled and jointly analyzed. CircRNA–miRNA–mRNA interactions were predicted by bioinformatics tools. The expression of interacting miRNAs and mRNA was verified in independent datasets. Survival analysis and pathway enrichment analysis were conducted on hub genes.

Results

We identified three significantly up-regulated circRNAs (hsa_circ_0009910, hsa_circ_0049783, and hsa_circ_0089172) both in HCC tissues and plasma samples. Two of them were validated to be indeed circular and could be excreted from hepatoma cells. We further revealed four miRNAs (hsa-miR-455-5p, hsa-miR-615-3p, hsa-miR-18a-3p, hsa-miR-4524a-3p) that targeting circRNAs and expressed in human HCC samples, and 95 mRNAs targeted by miRNAs and significantly up-regulated in two HCC cohorts. A protein-protein interaction network revealed 19 hub genes, 12 of them (MCM6, CCNB1, CDC20, NDC80, ZWINT, ASPM, CENPU, MCM3, MCM5, ECT2, CDC7, and DLGAP5) were associated with reduced survival in two HCC cohorts. KEGG, Reactome, and Wikipathway enrichment analysis indicated that the hub genes mainly functioned in DNA replication and cell cycle.

Conclusions

Our study uncovers three novel deregulated circRNAs in tumor and plasma from HCC patients and provides an insight into the pathogenesis from the circRNA–miRNA–mRNA regulatory network.
The epidemiology and detectability of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in low, moderate and high transmission settings in Ethiopia
Authors: Hailemeskel Elifaged , Tebeje Surafel K , Behaksra Sinknesh W. , Shumie Girma , Shitaye Getasew , Keffale Migbaru , Chali Wakweya , Gashaw Abrham , Ashine Temesgen , Drakeley Chris , Bousema Teun , Gadisa Endalamaw , Tadesse Fitsum G.
Published: January 2021

Background

As countries move to malaria elimination, detecting and targeting asymptomatic malaria infections might be needed. Here, the epidemiology and detectability of asymptomatic Plasmodium falciparum and Plasmodium vivax infections were investigated in different transmission settings in Ethiopia.

Method:

A total of 1093 dried blood spot (DBS) samples were collected from afebrile and apparently healthy individuals across ten study sites in Ethiopia from 2016 to 2020. Of these, 862 were from community and 231 from school based cross-sectional surveys. Malaria infection status was determined by microscopy or rapid diagnostics tests (RDT) and 18S rRNA-based nested PCR (nPCR). The annual parasite index (API) was used to classify endemicity as low (API > 0 and < 5), moderate (API ≥ 5 and < 100) and high transmission (API ≥ 100) and detectability of infections was assessed in these settings.

Results

In community surveys, the overall prevalence of asymptomatic Plasmodium infections by microscopy/RDT, nPCR and all methods combined was 12.2% (105/860), 21.6% (183/846) and 24.1% (208/862), respectively. The proportion of nPCR positive infections that was detectable by microscopy/RDT was 48.7% (73/150) for P. falciparum and 4.6% (2/44) for P. vivax. Compared to low transmission settings, the likelihood of detecting infections by microscopy/RDT was increased in moderate (Adjusted odds ratio [AOR]: 3.4; 95% confidence interval [95% CI] 1.6–7.2, P = 0.002) and high endemic settings (AOR = 5.1; 95% CI 2.6–9.9, P < 0.001). After adjustment for site and correlation between observations from the same survey, the likelihood of detecting asymptomatic infections by microscopy/RDT (AOR per year increase = 0.95, 95% CI 0.9–1.0, P = 0.013) declined with age.

Conclusions

Conventional diagnostics missed nearly half of the asymptomatic Plasmodium reservoir detected by nPCR. The detectability of infections was particularly low in older age groups and low transmission settings. These findings highlight the need for sensitive diagnostic tools to detect the entire parasite reservoir and potential infection transmitters.
Perceived social support and quality of life among adolescents in residential youth care: a cross-sectional study
Authors: Singstad Marianne Tevik , Wallander Jan Lance , Greger Hanne Klæboe , Lydersen Stian , Kayed Nanna Sønnichsen
Published: January 2021

Background

Residential youth care (RYC) institutions aim to provide care and stability for vulnerable adolescents with several previous and present challenges, such as disrupted attachments, wide-ranging adverse childhood experiences, mental health problems, and poor quality of life (QoL). To the best of our knowledge, the present study is the first to provide knowledge of the associations between perceived social support and QoL and to explore the potential moderating effect of perceived social support on QoL for adolescents who have experienced maltreatment and polyvictimization.

Methods

All RYC institutions with adolescents between the ages 12–23 in Norway were asked to participate in the study. A total of 86 institutions housing 601 adolescents accepted the invitation, from which 400 adolescents volunteered to participate. The Child and Adolescent Psychiatric Interview was used to gather information on maltreatment histories and degree of victimization; the Kinder Lebensqualität Fragebogen was used to measure QoL through several domains (overall QoL, physical well-being, emotional well-being, and self-esteem); and the Social Support Questionnaire was used to measure perceived social support. Linear regression and independent samples t-test were used to study the associations between perceived social support and QoL as well as the potential moderating effect of perceived social support in the association between maltreatment history and QoL.

Results

Perceived social support was positively associated with QoL for both girls and boys, with domain-specific findings. A higher number of different types of support persons was associated with overall QoL, emotional well-being, and self-esteem for boys, but only with self-esteem for girls. Individual social support from RYC staff and friends was associated with higher QoL for girls. However, perceived social support did not moderate the association between maltreatment history and reduced QoL for either sex.

Conclusions

This study emphasizes the importance of maintaining social support networks for adolescents living in RYC, the crucial contribution of RYC staff in facilitating social support, and the potential value of social skills training for these vulnerable adolescents. Furthermore, a wider range of initiatives beyond social support must be carried out to increase QoL among adolescents with major maltreatment and polyvictimization experiences.
Who could be One Health Activist at the community level?: A case for India
Authors: Yasobant Sandul , Bruchhausen Walter , Saxena Deepak , Memon Farjana Zakir , Falkenberg Timo
Published: January 2021

Background

Community health workers (CHWs) are the mainstay of the public health system, serving for decades in low-resource countries. Their multi-dimensional work in various health care services, including the prevention of communicable diseases and health promotion of non-communicable diseases, makes CHWs, the frontline workers in their respective communities in India. As India is heading towards the development of One Health (OH), this study attempted to provide an insight into potential OH activists (OHA) at the community level. Thus, this case study in one of India’s western cities, Ahmedabad, targeted identifying OHA by exploring the feasibility and the motivation of CHWs in a local setting.

Methods

This case study explores two major CHWs, i.e., female (Accredited Social Health Activists/ASHA) health workers (FHWs) and male (multipurpose) health workers (MHWs), on their experience and motivation for becoming an OHA. The data were collected between September 2018 and August 2019 through a mixed design, i.e., quantitative data (cross-sectional structured questionnaire) followed by qualitative data (focus group discussion with a semi-structured interview guide).

Results

The motivation of the CHWs for liaisoning as OHA was found to be low; however, the FHWs have a higher mean motivation score [40 (36–43)] as compared to MHWs [37 (35–40)] out of a maximum score of 92. Although most CHWs have received zoonoses training or contributed to zoonoses prevention campaigns, their awareness level was found to be different among male and female health workers. Comparing the female and male health workers to act as OHA, higher motivational score, multidisciplinary collaborative work experience, and way for incentive generation documented among the female health workers.

Conclusion

ASHAs were willing to accept the additional new liaison role of OHAs if measures like financial incentives and improved recognition are provided. Although this study documented various systemic factors at the individual, community, and health system level, which might, directly and indirectly, impact the acceptance level to act as OHA, they need to be accounted for in the policy regime.
How effective are physical activity interventions when they are scaled-up: a systematic review
Authors: Lane Cassandra , McCrabb Sam , Nathan Nicole , Naylor Patti-Jean , Bauman Adrian , Milat Andrew , Lum Melanie , Sutherland Rachel , Byaruhanga Judith , Wolfenden Luke
Published: January 2021

Background

The ‘scale-up’ of effective physical activity interventions is required if they are to yield improvements in population health. The purpose of this study was to systematically review the effectiveness of community-based physical activity interventions that have been scaled-up. We also sought to explore differences in the effect size of these interventions compared with prior evaluations of their efficacy in more controlled contexts, and describe adaptations that were made to interventions as part of the scale-up process.

Methods

We performed a search of empirical research using six electronic databases, hand searched reference lists and contacted field experts. An intervention was considered ‘scaled-up’ if it had been intentionally delivered on a larger scale (to a greater number of participants, new populations, and/or by means of different delivery systems) than a preceding randomised control trial (‘pre-scale’) in which a significant intervention effect (p < 0.05) was reported on any measure of physical activity. Effect size differences between pre-scale and scaled up interventions were quantified ([the effect size reported in the scaled-up study / the effect size reported in the pre-scale-up efficacy trial] × 100) to explore any scale-up ‘penalties’ in intervention effects.

Results

We identified 10 eligible studies. Six scaled-up interventions appeared to achieve significant improvement on at least one measure of physical activity. Six studies included measures of physical activity that were common between pre-scale and scaled-up trials enabling the calculation of an effect size difference (and potential scale-up penalty). Differences in effect size ranged from 132 to 25% (median = 58.8%), suggesting that most scaled-up interventions typically achieve less than 60% of their pre-scale effect size. A variety of adaptations were made for scale-up – the most common being mode of delivery.

Conclusion

The majority of interventions remained effective when delivered at-scale however their effects were markedly lower than reported in pre-scale trials. Adaptations of interventions were common and may have impacted on the effectiveness of interventions delivered at scale. These outcomes provide valuable insight for researchers and public health practitioners interested in the design and scale-up of physical activity interventions, and contribute to the growing evidence base for delivering health promotion interventions at-scale.

Trial registration

PROSPEROCRD42020144842.
"I was tricked": understanding reasons for unintended pregnancy among sexually active adolescent girls
Authors: Ajayi Anthony Idowu , Odunga Sally Atieno , Oduor Clement , Ouedraogo Ramatou , Ushie Boniface Ayanbekongshie , Wado Yohannes Dibaba
Published: January 2021

Background

While the Kenya government is mobilizing high-level strategies to end adolescent pregnancy by 2030, a clear understanding of drivers of early unintended pregnancy in the country is a necessary precursor. In this study, we determine the prevalence, associated factors, and reasons for unintended pregnancy among sexually active adolescent girls (aged 15–19 in two Kenya counties with the highest rate of teenage pregnancy.

Methods

We used the “In Their Hands” (ITH) program's baseline evaluation data. The study adopted a mixed-methods design with 1110 sexually active adolescent girls in the quantitative component and 19 girls who were either pregnant or nursing a child in the qualitative. We used adjusted and unadjusted logistic regression to model factors associated with unintended pregnancy among respondents. We used a thematic analysis of qualitative data to examine girls’ reasons for having unintended pregnancy.

Results

Overall, 42% of respondents have had an unintended pregnancy; however, higher proportions were observed among girls who were 19 years (49.4%), double orphans (53.6%), never used contraceptive (49.9%), out-of-school (53.8%), and married (55.6%). After adjusting for relevant covariates, the odds of unintended pregnancy were higher among girls who resided in rural areas (AOR 1.64, 95% CI 1.22–2.20), had primary or no formal education (AOR 1.50 95% CI 1.11–2.02), and had never used contraceptive (AOR 1.69 95% CI 1.25–2.29) compared with their counterparts. Current school attendance was associated with a 66% reduction in the probability of having an unintended pregnancy. Participants of the qualitative study stated that the desire to maintain a relationship, poor contraceptive knowledge, misinformation about contraceptive side effects, and lack of trusted mentors were the main reasons for their unintended pregnancies.

Conclusion

A massive burden of unintended pregnancy exists among sexually active adolescent girls in the study setting. Adolescent boys and girls need better access to sexuality education and contraceptives in the study setting to reduce early unintended pregnancy.
Detection of human papillomavirus genotypes, herpes simplex, varicella zoster and cytomegalovirus in breast cancer patients
Authors: Golrokh Mofrad Morvarid , Sadigh Zohreh Azita , Ainechi Sanaz , Faghihloo Ebrahim
Published: January 2021

Background

The role of viruses as a cause of breast cancer (BC) has been significantly investigated in recent years. Human papillomavirus (HPV) has been detected in invasive breast carcinomas, while most studies have only focused on the detection of viral DNA, we aimed to examine the prevalence and genotypes of HPV among Iranian BC patients.

We also examined the presence of herpes simplex-1 (HSV-1), herpes simplex-2 (HSV-2), varicella zoster virus (VZV), and cytomegalovirus (CMV) in these samples.

Methods

We collected and analyzed 70 Formalin-Fixed Paraffin-Embedded (FFPE) blocks including 59 BC samples, and 11 benign breast lesions as control from Iranian patients using nested PCR. Real-time PCR utilized as a confirming test to nested PCR findings. Genotyping of HPV positive samples was performed, the samples were also subjected to a multiplex PCR to detect HSV-1, HSV-2, VZV, and CMV in BC.

Results

Papillomavirus DNA was present in 7 of 59 BC samples (11.8%); while none was detected in control samples. The most prevalent type was HPV18, followed by HPV 6. All HPV positive patients had high tumor grades (II/ III) with a histologic diagnosis of ductal carcinoma. The patient age range was 33 to 73 years with a median of 51 years. Most of HPV positive patients had low levels of education. HPV16 was not detected. Also, 5 of 59 BC specimens (8.47%), were positive for HSV-1. But none of the samples were positive for HSV-2, VZV, and CMV.

Conclusions

Our results suggest a carcinogenesis role for High-risk HPV (HPV18) in breast tumors. Our findings of HSV-1 and low-risk HPV (HPV6) in BCs may propose a cancer-causing role for them. Further large-scale studies are warranted to assess the significance of our findings.
Atypical cells parameter in Sysmex UN automated urine analyzer: feedback from the field
Authors: Aydin Ozgur
Published: January 2021

Background

“Atypical cells” parameter in automated urinalysis has recently been introduced. An instrument capable of measuring quantitative and qualitative features of nuclear and cytoplasmic properties of a cell has the potential to detect cellular atypia. Instruments using flow cytometry have been detecting atypical cells in blood for a long time; yet instruments using the same methodology very lately developed this parameter in urinalysis.

Materials and methods

Samples with an atypical cells value higher than 1 atypical cell/µL were included in the study. Besides automated urinalysis, every sample was reflexed to modular unit for digital imaging. The remainder of each sample was stained with Sternheimer dye and examined manually under a light microscope.

Results

50 samples with higher than1 atypical cell/µL result were included in the study. Patients were composed of 43 females (86 %) and 7 males (14 %). The mean age was 47.12 ± 19.45 years. The median atypical cells value was 1.8/µL (95 % range 1.5–2.4/µL). Manual microscopic evaluation of the 50 samples showed atypical cells in 1 sample. The patient had papillary lesions on cystoscopy and pathology report informed a high grade urothelial carcinoma. Other 49 samples were negative for atypical cells in manual microscopy. They were crowded samples with leucocytes and squamous epithelial cells.

Conclusions

The positive case provided evidence for Sysmex UN’s capability to detect atypical cells in urine. The negative cases presented clues that probable vulvovaginal contamination and crowded specimens could be deceptive for Sysmex UN in this particular parameter.
Efficacy of additional corticosteroids to multimodal cocktail periarticular injection in total knee arthroplasty: a meta-analysis of randomized controlled trials
Authors: Li Qi , Mu Guo , Liu Xiangbo , Chen Milian
Published: January 2021

Background

As the ultimate method for the treatment of osteoarthritis, total knee arthroplasty (TKA) has been widely used in the clinic. Local injection of multimodal cocktails, including corticosteroids, is commonly used for pain management after TKA. This meta-analysis aims to systematically evaluate the effect of periarticular injection of corticosteroids on postoperative pain relief and knee functional recovery in patients undergoing TKA.

Methods

PubMed, Cochrane Library, EMBASE, and Web of Science databases were comprehensively searched for all randomized controlled trials (RCTs) published before July 1, 2020, that investigated the efficacy of corticosteroids for TKA.

Results

Ten RCTs involving a total of 829 patients were assessed in the meta-analysis. Compared with the control group, the visual analogue scale (VAS) score at rest of the corticosteroid group decreased significantly at postoperative day 1 (POD1), POD2, and POD3 (p< 0.05). Besides, the range of flexion motion of the knee joint in the corticosteroid group at POD1 and POD2 was significantly increased (p< 0.05); at the same time, the range of extension motion at POD2 and POD3 showed the opposite trend between the two groups (p< 0.05). The morphine equivalent of postoperative analgesia was significantly reduced (p< 0.05), and the time required for straight leg raising (SLR) was significantly shortened (p< 0.05). There was no significant difference between the two groups in terms of postoperative drainage, length of hospital stay, and complications such as infection, nausea, and vomiting (p> 0.05).

Conclusion

The additional corticosteroids to multimodal cocktail periarticular injection can relieve the early pain intensity at rest after TKA, increase the early range of motion (ROM) of the knee joint, reduce the dosage of postoperative analgesics, and shorten the duration of time required for SLR. However, it has no effect on reducing postoperative complications and shortening the length of hospital stay.
tidybulk: an R tidy framework for modular transcriptomic data analysis
Authors: Mangiola Stefano , Molania Ramyar , Dong Ruining , Doyle Maria A. , Papenfuss Anthony T.
Published: January 2021

Recently, efforts have been made toward the harmonization of transcriptomic data structures and workflows using the concept of data tidiness, to facilitate modularisation. We present tidybulk, a modular framework for bulk transcriptional analyses that introduces a tidy transcriptomic data structure paradigm and analysis grammar. Tidybulk covers a wide variety of analysis procedures and integrates a large ecosystem of publicly available analysis algorithms under a common framework. Tidybulk decreases coding burden, facilitates reproducibility, increases efficiency for expert users, lowers the learning curve for inexperienced users, and bridges transcriptional data analysis with the tidyverse. Tidybulk is available at R/Bioconductorbioconductor.org/packages/tidybulk.
Effectiveness of a pathway-driven eHealth-based integrated care model (PEICM) for community-based hypertension management in China: study protocol for a randomized controlled trial
Authors: Wang Zheyu , Li Chengling , Huang Wencai , Chen Yan , Li Yuqiong , Huang Libin , Zhang Mei , Wu Dan , Wang Li , Duan Huilong , An Jiye , Deng Ning
Published: January 2021

Background

The prevalence of hypertension is high and increasing in China in recent years. The treatment and control of hypertension calls for long-term management beyond hospital, which is hard to implement in traditional care settings. Integrated care combined with information technology can promote high-quality healthcare services across the life-course. However, few studies have applied a customized integrated care model in community-based hypertension management in China, catering to the emerging “three-manager” mode. This study aims to identify the effectiveness of a pathway-driven eHealth-based integrated model that implemented as a full-featured telehealth system to facilitate standardized management of hypertension in China.

Methods

The trial has been designed as a 1-year, non-blinded superiority trial with two parallel groups. A total of 402 hypertensive patients who meet the eligibility criteria will be recruited and randomized with a 1:1 allocation. All the participants will receive a mobile device for self-management, which is a part of our telehealth system. Participants in the control group will only use the device for BP measurement and receive regular follow-ups from care providers according to the guidelines. Participants in the intervention group will gain full access to the system and receive intervention based on the proposed model (a well-designed coordinated care pathway consisting of 9 tasks). Outcomes will be measured mainly on three occasions (at inclusion, at 6 months, and at 12 months). The primary outcome is mean change in systolic blood pressure over a 12-month period. Secondary outcomes include changes in diastolic blood pressure, biochemical indexes related to hypertension, lifestyles, self-management adherence, and hypertension awareness, as well as work efficiency of care providers.

Discussion

This study aims to investigate whether a pathway-driven eHealth-based integrated care model based on the “three-manager” mode will improve hypertension control in China. Success of the model would help improve the quality of present community-based management procedures and benefit more patients with uncontrolled hypertension.

Trial registration

Chinese Clinical Trial Registry ChiCTR1900027645. Registered on November 22, 2019.
Oral melatonin as a new tool for neuroprotection in preterm newborns: study protocol for a randomized controlled trial
Authors: Garofoli Francesca , Longo Stefania , Pisoni Camilla , Accorsi Patrizia , Angelini Micol , Aversa Salvatore , Caporali Camilla , Cociglio Sara , De Silvestri Annalisa , Fazzi Elisa , Rizzo Vittoria , Tzialla Chryssoula , Zecca Marco , Orcesi Simona
Published: January 2021

Background

Prevention of neurodevelopmental impairment due to preterm birth is a major health challenge. Despite advanced obstetric and neonatal care, to date there are few neuroprotective molecules available. Melatonin has been shown to have anti-oxidant/anti-inflammatory effects and to reduce brain damage, mainly after hypoxic ischemic encephalopathy. The planned study will be the first aiming to evaluate the capacity of melatonin to mitigate brain impairment due to premature birth.

Method

In our planned prospective, multicenter, double-blind, randomized vs placebo study, we will recruit, within 96 h of birth, 60 preterm newborns with a gestational age ≤ 29 weeks + 6 days; these infants will be randomly allocated to oral melatonin, 3 mg/kg/day, or placebo for 15 days. After the administration period, we will measure plasma levels of malondialdehyde, a lipid peroxidation product considered an early biological marker of melatonin treatment efficacy (primary outcome). At term-equivalent age, we will evaluate neurological status (through cerebral ultrasound, cerebral magnetic resonance imaging, vision and hearing evaluations, clinical neurological assessment, and screening for retinopathy of prematurity) as well as the incidence of bronchodysplasia and sepsis. We will also monitor neurodevelopmental outcome during the first 24 months of corrected age (using the modified Fagan Test of Infant Intelligence at 4–6 months and standardized neurological and developmental assessments at 24 months).

Discussion

Preterm birth survivors often present long-term neurodevelopmental sequelae, such as motor, learning, social-behavioral, and communication problems. We aim to assess the role of melatonin as a neuroprotectant during the first weeks of extrauterine life, when preterm infants are unable to produce it spontaneously. This approach is based on the supposition that its anti-oxidant mechanism could be useful in preventing neurodevelopmental impairment. Considering the short- and long-term morbidities related to preterm birth, and the financial and social costs of the care of preterm infants, both at birth and over time, we suggest that melatonin administration could lead to considerable saving of resources. This would be the first study addressing the role of melatonin in very low birth weight preterm newborns, and it could provide a basis for further studies on melatonin as a neuroprotection strategy in this vulnerable population.

Trial registration

ClinicalTrials.gov NCT04235673. Prospectively registered on 22 January 2020.
Understanding mosquito host-choice behaviour: a new and low-cost method of identifying the sex of human hosts from mosquito blood meals
Authors: Teltscher Fiona , Bouvaine Sophie , Gibson Gabriella , Dyer Paul , Guest Jennifer , Young Stephen , Hopkins Richard J.
Published: January 2021

Background

Mosquito-borne diseases are a global health problem, causing hundreds of thousands of deaths per year. Pathogens are transmitted by mosquitoes feeding on the blood of an infected host and then feeding on a new host. Monitoring mosquito host-choice behaviour can help in many aspects of vector-borne disease control. Currently, it is possible to determine the host species and an individual human host from the blood meal of a mosquito by using genotyping to match the blood profile of local inhabitants. Epidemiological models generally assume that mosquito biting behaviour is random; however, numerous studies have shown that certain characteristics, e.g. genetic makeup and skin microbiota, make some individuals more attractive to mosquitoes than others. Analysing blood meals and illuminating host-choice behaviour will help re-evaluate and optimise disease transmission models.

Methods

We describe a new blood meal assay that identifies the sex of the person that a mosquito has bitten. The amelogenin locus (AMEL), a sex marker located on both X and Y chromosomes, was amplified by polymerase chain reaction in DNA extracted from blood-fed Aedes aegypti and Anopheles coluzzii.

Results

AMEL could be successfully amplified up to 24 h after a blood meal in 100% of An. coluzzii and 96.6% of Ae. aegypti, revealing the sex of humans that were fed on by individual mosquitoes.

Conclusions

The method described here, developed using mosquitoes fed on volunteers, can be applied to field-caught mosquitoes to determine the host species and the biological sex of human hosts on which they have blood fed. Two important vector species were tested successfully in our laboratory experiments, demonstrating the potential of this technique to improve epidemiological models of vector-borne diseases. This viable and low-cost approach has the capacity to improve our understanding of vector-borne disease transmission, specifically gender differences in exposure and attractiveness to mosquitoes. The data gathered from field studies using our method can be used to shape new transmission models and aid in the implementation of more effective and targeted vector control strategies by enabling a better understanding of the drivers of vector-host interactions.

Graphical Abstract
Private and rateless adaptive coded matrix-vector multiplication
Authors: Bitar Rawad , Xing Yuxuan , Keshtkarjahromi Yasaman , Dasari Venkat , El Rouayheb Salim , Seferoglu Hulya
Published: January 2021

Edge computing is emerging as a new paradigm to allow processing data near the edge of the network, where the data is typically generated and collected. This enables critical computations at the edge in applications such as Internet of Things (IoT), in which an increasing number of devices (sensors, cameras, health monitoring devices, etc.) collect data that needs to be processed through computationally intensive algorithms with stringent reliability, security and latency constraints. Our key tool is the theory of coded computation, which advocates mixing data in computationally intensive tasks by employing erasure codes and offloading these tasks to other devices for computation. Coded computation is recently gaining interest, thanks to its higher reliability, smaller delay, and lower communication costs. In this paper, we develop a private and rateless adaptive coded computation (PRAC) algorithm for distributed matrix-vector multiplication by taking into account (1) the privacy requirements of IoT applications and devices, and (2) the heterogeneous and time-varying resources of edge devices. We show that PRAC outperforms known secure coded computing methods when resources are heterogeneous. We provide theoretical guarantees on the performance of PRAC and its comparison to baselines. Moreover, we confirm our theoretical results through simulations and implementations on Android-based smartphones.
Orthogonality in smooth countably normed spaces
Authors: Tawfeek Sarah , Faried Nashat , El-Sharkawy H. A.
Published: January 2021

We generalize the concepts of normalized duality mapping, J-orthogonality and Birkhoff orthogonality from normed spaces to smooth countably normed spaces. We give some basic properties of J-orthogonality in smooth countably normed spaces and show a relation between J-orthogonality and metric projection on smooth uniformly convex complete countably normed spaces. Moreover, we define the J-dual cone and J-orthogonal complement on a nonempty subset S of a smooth countably normed space and prove some basic results about the J-dual cone and the J-orthogonal complement of S.
The base of warped product submanifolds of Sasakian space forms characterized by differential equations
Authors: Ali Akram , Agrawal Ravi P. , Mofarreh Fatemah , Alluhaibi Nadia
Published: January 2021

In the present paper, we find some characterization theorems. Under certain pinching conditions on the warping function satisfying some differential equation, we show that the base of warped product submanifolds of a Sasakian space form $\widetilde{M}^{2m+1}(\epsilon )$

M
˜

2
m
+
1

(
ϵ
)
is isometric either to a Euclidean space $\mathbb{R}^{n}$

R
n

or a warped product of a complete manifold N and the Euclidean line $\mathbb{R}$
R
.
Identification of microbial signatures linked to oilseed rape yield decline at the landscape scale
Authors: Hilton Sally , Picot Emma , Schreiter Susanne , Bass David , Norman Keith , Oliver Anna E. , Moore Jonathan D. , Mauchline Tim H. , Mills Peter R. , Teakle Graham R. , Clark Ian M. , Hirsch Penny R. , van der Gast Christopher J. , Bending Gary D.
Published: January 2021

Background

The plant microbiome plays a vital role in determining host health and productivity. However, we lack real-world comparative understanding of the factors which shape assembly of its diverse biota, and crucially relationships between microbiota composition and plant health. Here we investigated landscape scale rhizosphere microbial assembly processes in oilseed rape (OSR), the UK’s third most cultivated crop by area and the world's third largest source of vegetable oil, which suffers from yield decline associated with the frequency it is grown in rotations. By including 37 conventional farmers’ fields with varying OSR rotation frequencies, we present an innovative approach to identify microbial signatures characteristic of microbiomes which are beneficial and harmful to the host.

Results

We show that OSR yield decline is linked to rotation frequency in real-world agricultural systems. We demonstrate fundamental differences in the environmental and agronomic drivers of protist, bacterial and fungal communities between root, rhizosphere soil and bulk soil compartments. We further discovered that the assembly of fungi, but neither bacteria nor protists, was influenced by OSR rotation frequency. However, there were individual abundant bacterial OTUs that correlated with either yield or rotation frequency. A variety of fungal and protist pathogens were detected in roots and rhizosphere soil of OSR, and several increased relative abundance in root or rhizosphere compartments as OSR rotation frequency increased. Importantly, the relative abundance of the fungal pathogen Olpidium brassicae both increased with short rotations and was significantly associated with low yield. In contrast, the root endophyte Tetracladium spp. showed the reverse associations with both rotation frequency and yield to O. brassicae, suggesting that they are signatures of a microbiome which benefits the host. We also identified a variety of novel protist and fungal clades which are highly connected within the microbiome and could play a role in determining microbiome composition.

Conclusions

We show that at the landscape scale, OSR crop yield is governed by interplay between complex communities of both pathogens and beneficial biota which is modulated by rotation frequency. Our comprehensive study has identified signatures of dysbiosis within the OSR microbiome, grown in real-world agricultural systems, which could be used in strategies to promote crop yield.
Quantifying fluorescent glycan uptake to elucidate strain-level variability in foraging behaviors of rumen bacteria
Authors: Klassen Leeann , Reintjes Greta , Tingley Jeffrey P. , Jones Darryl R. , Hehemann Jan-Hendrik , Smith Adam D. , Schwinghamer Timothy D. , Arnosti Carol , Jin Long , Alexander Trevor W. , Amundsen Carolyn , Thomas Dallas , Amann Rudolf , McAllister Tim A. , Abbott D. Wade
Published: January 2021

Gut microbiomes, such as the microbial community that colonizes the rumen, have vast catabolic potential and play a vital role in host health and nutrition. By expanding our understanding of metabolic pathways in these ecosystems, we will garner foundational information for manipulating microbiome structure and function to influence host physiology. Currently, our knowledge of metabolic pathways relies heavily on inferences derived from metagenomics or culturing bacteria in vitro. However, novel approaches targeting specific cell physiologies can illuminate the functional potential encoded within microbial (meta)genomes to provide accurate assessments of metabolic abilities. Using fluorescently labeled polysaccharides, we visualized carbohydrate metabolism performed by single bacterial cells in a complex rumen sample, enabling a rapid assessment of their metabolic phenotype. Specifically, we identified bovine-adapted strains ofBacteroides thetaiotaomicronthat metabolized yeast mannan in the rumen microbiome ex vivo and discerned the mechanistic differences between two distinct carbohydrate foraging behaviors, referred to as “medium grower” and “high grower.” Using comparative whole-genome sequencing, RNA-seq, and carbohydrate-active enzyme fingerprinting, we could elucidate the strain-level variability in carbohydrate utilization systems of the two foraging behaviors to help predict individual strategies of nutrient acquisition. Here, we present a multi-faceted study using complimentary next-generation physiology and “omics” approaches to characterize microbial adaptation to a prebiotic in the rumen ecosystem.
Coexistence patterns of soil methanogens are closely tied to methane generation and community assembly in rice paddies
Authors: Li Dong , Ni Haowei , Jiao Shuo , Lu Yahai , Zhou Jizhong , Sun Bo , Liang Yuting
Published: January 2021

Background

Soil methanogens participate in complex interactions, which determine the community structures and functions. Studies continue to seek the coexistence patterns of soil methanogens, influencing factors and the contribution to methane (CH4) production, which are regulated primarily by species interactions, and the functional significance of these interactions. Here, methane emissions were measured in rice paddies across the Asian continent, and the complex interactions involved in coexistence patterns of methanogenic archaeal communities were represented as pairwise links in co-occurrence networks.

Results

The network topological properties, which were positively correlated with mean annual temperature, were the most important predictor of CH4 emissions among all the biotic and abiotic factors. The methanogenic groups involved in commonly co-occurring links among the 39 local networks contributed most to CH4 emission (53.3%), much higher than the contribution of methanogenic groups with endemic links (36.8%). The potential keystone taxa, belonging to Methanobacterium, Methanocella, Methanothrix, and Methanosarcina, possessed high linkages with the methane generation functional genes mcrA, fwdB, mtbA, and mtbC. Moreover, the commonly coexisting taxa showed a very different assembly pattern, with ~ 30% determinism and ~ 70% stochasticity. In contrast, a higher proportion of stochasticity (93~99%) characterized the assembly of endemically coexisting taxa.

Conclusions

These results suggest that the coexistence patterns of microbes are closely tied to their functional significance, and the potential importance of common coexistence further imply that complex networks of interactions may contribute more than species diversity to soil functions.
Correction to: Rhizosphere microbiomes diverge among Populus trichocarpa plant-host genotypes and chemotypes, but it depends on soil origin
Authors: Veach Allison M. , Morris Reese , Yip Daniel Z. , Yang Zamin K. , Engle Nancy L. , Cregger Melissa A. , Tschaplinski Timothy J. , Schadt Christopher W.
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.
SIRT6 enhances oxidative phosphorylation in breast cancer and promotes mammary tumorigenesis in mice
Authors: Becherini Pamela , Caffa Irene , Piacente Francesco , Damonte Patrizia , Vellone Valerio G. , Passalacqua Mario , Benzi Andrea , Bonfiglio Tommaso , Reverberi Daniele , Khalifa Amr , Ghanem Moustafa , Guijarro Ana , Tagliafico Luca , Sucameli Marzia , Persia Angelica , Monacelli Fiammetta , Cea Michele , Bruzzone Santina , Ravera Silvia , Nencioni Alessio
Published: January 2021

Background

Sirtuin 6 (SIRT6) is a NAD+-dependent deacetylase with key roles in cell metabolism. High SIRT6 expression is associated with adverse prognosis in breast cancer (BC) patients. However, the mechanisms through which SIRT6 exerts its pro-oncogenic effects in BC remain unclear. Here, we sought to define the role of SIRT6 in BC cell metabolism and in mouse polyoma middle T antigen (PyMT)-driven mammary tumors.

Methods

We evaluated the effect of a heterozygous deletion of Sirt6 on tumor latency and survival of mouse mammary tumor virus (MMTV)-PyMT mice. The effect of SIRT6 silencing on human BC cell growth was assessed in MDA-MB-231 xenografts. We also analyzed the effect of Sirt6 heterozygous deletion, of SIRT6 silencing, and of the overexpression of either wild-type (WT) or catalytically inactive (H133Y) SIRT6 on BC cell pyruvate dehydrogenase (PDH) expression and activity and oxidative phosphorylation (OXPHOS), including respiratory complex activity, ATP/AMP ratio, AMPK activation, and intracellular calcium concentration.

Results

The heterozygous Sirt6 deletion extended tumor latency and mouse survival in the MMTV-PyMT mouse BC model, while SIRT6 silencing slowed the growth of MDA-MB-231 BC cell xenografts. WT, but not catalytically inactive, SIRT6 enhanced PDH expression and activity, OXPHOS, and ATP/AMP ratio in MDA-MB-231 and MCF7 BC cells. Opposite effects were obtained by SIRT6 silencing, which also blunted the expression of genes encoding for respiratory chain proteins, such as UQCRFS1, COX5B, NDUFB8, and UQCRC2, and increased AMPK activation in BC cells. In addition, SIRT6 overexpression increased, while SIRT6 silencing reduced, intracellular calcium concentration in MDA-MB-231 cells. Consistent with these findings, the heterozygous Sirt6 deletion reduced the expression of OXPHOS-related genes, the activity of respiratory complexes, and the ATP/AMP ratio in tumors isolated from MMTV-PyMT mice.

Conclusions

Via its enzymatic activity, SIRT6 enhances PDH expression and activity, OXPHOS, ATP/AMP ratio, and intracellular calcium concentration, while reducing AMPK activation, in BC cells. Thus, overall, SIRT6 inhibition appears as a viable strategy for preventing or treating BC.
Dispositional individual differences in cognitive effort investment: establishing the core construct
Authors: Kührt Corinna , Pannasch Sebastian , Kiebel Stefan J. , Strobel Alexander
Published: January 2021

Background

Individuals tend to avoid effortful tasks, regardless of whether they are physical or mental in nature. Recent experimental evidence is suggestive of individual differences in the dispositional willingness to invest cognitive effort in goal-directed behavior. The traits need for cognition (NFC) and self-control are related to behavioral measures of cognitive effort discounting and demand avoidance, respectively. Given that these traits are only moderately related, the question arises whether they reflect a common core factor underlying cognitive effort investment. If so, the common core of both traits might be related to behavioral measures of effort discounting in a more systematic fashion. To address this question, we aimed at specifying a core construct of cognitive effort investment that reflects dispositional differences in the willingness and tendency to exert effortful control.

Methods

We conducted two studies (N = 613 andN = 244) with questionnaires related to cognitive motivation and effort investment including assessment of NFC, intellect, self-control and effortful control. We first calculated Pearson correlations followed by two mediation models regarding intellect and its separate aspects,seekandconquer, as mediators. Next, we performed a confirmatory factor analysis of a hierarchical model of cognitive effort investment as second-order latent variable. First-order latent variables were cognitive motivation reflecting NFC and intellect, and effortful self-control reflecting self-control and effortful control. Finally, we calculated Pearson correlations between factor scores of the latent variables and general self-efficacy as well as traits of the Five Factor Model of Personality for validation purposes.

Results

Our findings support the hypothesized correlations between the assessed traits, where the relationship of NFC and self-control is specifically mediated via goal-directedness. We established and replicated a hierarchical factor model of cognitive motivation and effortful self-control that explains the shared variance of the first-order factors by a second-order factor of cognitive effort investment.

Conclusions

Taken together, our results integrate disparate literatures on cognitive motivation and self-control and provide a basis for further experimental research on the role of dispositional individual differences in goal-directed behavior and cost–benefit-models.