bluuebunny/crossref_metadata_2025 huggingface dataset:
Photoionization cross sections of ultracold 88Sr in 1P1 and 3S1 states at 390 nm and the resulting blue-detuned magic wavelength optical lattice clock constraints
Authors: Witkowski Marcin , Bilicki Sławomir , Bober Marcin , Kovačić Domagoj , Singh Vijay , Tonoyan Ara , Zawada Michał
Published: May 2022

We present the measurements of the photoionization cross sections of the excited 1P1 and 3S1 states of ultracold 88Sr atoms at 389.889 nm wavelength, which is the magic wavelength of the 1S0-3P0 clock transition. The photoionization cross section of the 1P1 state is determined from the measured ionization rates of 88Sr in the magneto-optical trap in the 1P1 state to be 2.20(50)×10−20 m2, while the photoionization cross section of 88Sr in the 3S1 state is inferred from the photoionization-induced reduction in the number of atoms transferred through the 3S1 state in an operating optical lattice clock to be 1.38(66) ×10−18 m2. Furthermore, the resulting limitations of employing a blue-detuned magic wavelength optical lattice in strontium optical lattice clocks are evaluated. We estimated photoionization induced loss rates of atoms at 389.889 nm wavelength under typical experimental conditions and made several suggestions on how to mitigate these losses. In particular, the large photoionization induced losses for the 3S1 state would make the use of the 3S1 state in the optical cycle in a blue-detuned optical lattice unfeasible and would instead require the less commonly used 3D1,2 states during the detection part of the optical clock cycle.
Dynamics of dissipative soliton molecules in a dual-wavelength ultrafast fiber laser
Authors: Zhou Yi , Ren Yu-xuan , Shi Jiawei , Wong Kenneth K. Y.
Published: May 2022

Optical solitons, particle-like excitations ubiquitous in many fields, can bind to form soliton molecules with striking molecule-like interactions. However, the exotic soliton interactions in soliton molecules are still largely unexplored in dual-wavelength mode-locked fiber lasers. Here, we reveal the dynamics of dissipative soliton molecules with periodic solitons collision in a dual-wavelength ultrafast fiber laser. The soliton molecules with a central wavelength of 1532.8 nm and 1561 nm exhibit conspicuously different evolution characteristics attributed to the difference in gain spectral intensity and trapped potential. The long-wavelength soliton molecule swiftly recovers to the initial state after collision, while the short-wavelength soliton molecule has a remarkable variation in temporal separation and operation state. Moreover, the multiple intensive repulsion and attraction in soliton molecule with energy transfer between leading and trailing solitons, and the formation of triplet soliton molecule in short-wavelength with multiple switching have also been observed. The different oscillating solutions coexisting in dual-wavelength soliton molecules involving oscillating and sliding phase evolution confirm the multistability of the dissipative system. These findings shed new insights into the dynamics of soliton molecules and solitons collision in nonlinear systems.
Automated bone cell classification for confocal laser scanning microscopy volumes
Authors: Flannery Brennan T. , Xu Xiaoyu , Golz Brian T. , Main Russell P.
Published: May 2022

Manual cell classification in microscopy images is a time-consuming process that heavily relies on the subjective perception of the investigator. Identifying bone cells introduces additional difficulties with irregular geometries, and in some culture conditions, the presence of bone mineral. As fluorescence-based lineage tracing becomes more common, classifying cell types based upon cell color can further increase subjectivity. Our goal is to develop and validate a fully automated cell classification algorithm that can (i) objectively identify cells in flattened volumetric image stacks from three-dimensional (3D) bone cell cultures and (ii) classify the cells (osteoblast-lineage) based on the color of their cell bodies. The algorithm used here was developed in MATLAB 2019a and validated by comparing code outputs to manual labeling for eleven images. The precision, recall, and F1 scores were higher than 0.75 for all cell classifications, with the majority being greater than 0.80. No significant differences were found between the manually labelled and automated cell counts or cell classifications. Analysis time for a single image averaged seventeen seconds compared to more than ten minutes for manual labeling. This demonstrates that the program offers a fast, repeatable, and accurate way to classify bone cells by fluorescence in confocal microscopy image data sets. This process can be expanded to improve investigation of other pre-clinical models and histological sections of pathological tissues where color or fluorescence-based differences are used for cell identification.
Multiple molecular events underlie stochastic switching between 2 heritable cell states in fungi
Authors: Ziv Naomi , Brenes Lucas R. , Johnson Alexander
Published: May 2022

Eukaryotic transcriptional networks are often large and contain several levels of feedback regulation. Many of these networks have the ability to generate and maintain several distinct transcriptional states across multiple cell divisions and to switch between them. In certain instances, switching between cell states is stochastic, occurring in a small subset of cells of an isogenic population in a seemingly homogenous environment. Given the scarcity and unpredictability of switching in these cases, investigating the determining molecular events is challenging. White-opaque switching in the fungal species Candida albicans is an example of stably inherited cell states that are determined by a complex transcriptional network and can serve as an experimentally accessible model system to study characteristics important for stochastic cell fate switching in eukaryotes. In standard lab media, genetically identical cells maintain their cellular identity (either “white” or “opaque”) through thousands of cell divisions, and switching between the states is rare and stochastic. By isolating populations of white or opaque cells, previous studies have elucidated the many differences between the 2 stable cell states and identified a set of transcriptional regulators needed for cell type switching and maintenance of the 2 cell types. Yet, little is known about the molecular events that determine the rare, stochastic switching events that occur in single cells. We use microfluidics combined with fluorescent reporters to directly observe rare switching events between the white and opaque states. We investigate the stochastic nature of switching by beginning with white cells and monitoring the activation of Wor1, a master regulator and marker for the opaque state, in single cells and throughout cell pedigrees. Our results indicate that switching requires 2 stochastic steps; first an event occurs that predisposes a lineage of cells to switch. In the second step, some, but not all, of those predisposed cells rapidly express high levels of Wor1 and commit to the opaque state. To further understand the rapid rise in Wor1, we used a synthetic inducible system in Saccharomyces cerevisiae into which a controllable C. albicans Wor1 and a reporter for its transcriptional control region have been introduced. We document that Wor1 positive autoregulation is highly cooperative (Hill coefficient > 3), leading to rapid activation and producing an “all or none” rather than a graded response. Taken together, our results suggest that reaching a threshold level of a master regulator is sufficient to drive cell type switching in single cells and that an earlier molecular event increases the probability of reaching that threshold in certain small lineages of cells. Quantitative molecular analysis of the white-opaque circuit can serve as a model for the general understanding of complex circuits.
Regulation of PDF receptor signaling controlling daily locomotor rhythms in Drosophila
Authors: Li Weihua , Trigg Jennifer S. , Taghert Paul H.
Published: May 2022

Each day and in conjunction with ambient daylight conditions, neuropeptide PDF regulates the phase and amplitude of locomotor activity rhythms in Drosophila through its receptor, PDFR, a Family B G protein-coupled receptor (GPCR). We studied the in vivo process by which PDFR signaling turns off, by converting as many as half of the 28 potential sites of phosphorylation in its C terminal tail to a non-phosphorylatable residue (alanine). We report that many such sites are conserved evolutionarily, and their conversion creates a specific behavioral syndrome opposite to loss-of-function phenotypes previously described for pdfr. That syndrome includes increases in the amplitudes of both Morning and Evening behavioral peaks, as well as multi-hour delays of the Evening phase. The precise behavioral effects were dependent on day-length, and most effects mapped to conversion of only a few, specific serine residues near the very end of the protein and specific to its A isoform. Behavioral phase delays of the Evening activity under entraining conditions predicted the phase of activity cycles under constant darkness. The behavioral phenotypes produced by the most severe PDFR variant were ligand-dependent in vivo, and not a consequence of changes to their pharmacological properties, nor of changes in their surface expression, as measured in vitro. The mechanisms underlying termination of PDFR signaling are complex, subject to regulation that is modified by season, and central to a better understanding of the peptidergic modulation of behavior.
What the snake leaves in its wake: Functional limitations and disabilities among snakebite victims in Ghanaian communities
Authors: Aglanu Leslie Mawuli , Amuasi John Humphrey , Schut Bob A. , Steinhorst Jonathan , Beyuo Alexis , Dari Chrisantus Danaah , Agbogbatey Melvin Katey , Blankson Emmanuel Steve , Punguyire Damien , Lalloo David G. , Blessmann Jörg , Abass Kabiru Mohammed , Harrison Robert A. , Stienstra Ymkje
Published: May 2022

Background

The estimated five million snakebites per year are an important health problem that mainly affect rural poor populations. The global goal is to halve both mortality and morbidity from this neglected tropical disease by 2030. Data on snakebite morbidity are sparse and mainly obtained from hospital records.

Methods

This community-based study was conducted among 379 rural residents with or without a history of snakebite in the Ashanti and Upper West regions of Ghana. All participants in the snakebite group were bitten at least six months before the day of survey. The World Health Organisation Disability Assessment Schedule 2.0 (WHODAS 2.0) and the Buruli Ulcer Functional Limitation Score were used to obtain patient-reported measure of functioning and disability. Long-term consequences were evaluated based on the severity of the symptoms at the time of the snakebite.

Findings

The median (IQR) time since the snakebite was 8.0 (3.5–16.5) years. The relative risk of disability was 1.54 (95% CI, 1.17–2.03) in the snakebite group compared to the community controls. Among patients with clinical symptoms suggesting envenoming at the time of bite, 35% had mild/moderate disabilities compared to 20% in the control group. The disability domains mainly affected by snakebite envenoming were cognition level, mobility, life activities and participation in society. A combination of the severity of symptoms at the time of the bite, age, gender and region of residence most accurately predicted the odds of having functional limitations and disabilities.

Conclusion

The burden of snakebite in the community includes long-term disabilities of mild to moderate severity, which need to be considered when designing appropriate public health interventions. Estimating the total burden of snakebite is complicated by geographic differences in types of snakes and their clinical manifestations.
Characterization of a novel microfilarial antigen for diagnosis of Wuchereria bancrofti infections
Authors: Greene Sarah E. , Fischer Kerstin , Choi Young-Jun , Curtis Kurt C. , Budge Philip J. , Mitreva Makedonka , King Christopher L. , Fischer Peter U. , Weil Gary J.
Published: May 2022

Background

Lymphatic filariasis (LF) is a neglected tropical disease caused by the filarial nematodes Wuchereria bancrofti, Brugia malayi and Brugia timori. The Global Program to Eliminate LF uses mass drug administration (MDA) of anti-filarial drugs that clear microfilariae (Mf) from blood to interrupt transmission by mosquitos. New diagnostic tools are needed to assess the impact of MDA on bancroftian filariasis, because available serologic tests can remain positive after successful treatment.

Methodology/Principal findings

We identified Wb-bhp-1, which encodes a W. bancrofti homologue of BmR1, the B. malayi protein used in the Brugia Rapid antibody test for brugian filariasis. Wb-bhp-1 has a single exon that encodes a 16.3 kD protein (Wb-Bhp-1) with 45% amino acid identity to BmR1. Immunohistology shows that anti-Wb-Bhp-1 antibodies primarily bind to Mf. Plasma from 124 of 224 (55%) microfilaremic individuals had IgG4 antibodies to Wb-Bhp-1 by ELISA. Serologic reactivity to Wb-Bhp-1 varied widely with samples from different regions (sensitivity range 32–92%), with 77% sensitivity for 116 samples collected from microfilaremic individuals outside of sub-Saharan Africa. This variable sensitivity highlights the importance of validating new diagnostic tests for parasitic diseases with samples from different geographical regions. Individuals with higher Mf counts were more likely to have anti-Wb-Bhp-1 antibodies. Cross-reactivity was observed with a minority of plasma samples from people with onchocerciasis (17%) or loiasis (10%). We also identified, cloned and characterized BmR1 homologues from O. volvulus and L. loa that have 41% and 38% identity to BmR1, respectively. However, antibody assays with these antigens were not sensitive for onchocerciasis or loiasis.

Conclusions

Wb-Bhp-1 is a novel antigen that is useful for serologic diagnosis of bancroftian filariasis. Additional studies are needed to assess the value of this antigen for monitoring the success of filariasis elimination programs.
Transmission dynamics and vaccination strategies for Crimean-Congo haemorrhagic fever virus in Afghanistan: A modelling study
Authors: Vesga Juan F. , Clark Madeleine H. A. , Ayazi Edris , Apolloni Andrea , Leslie Toby , Edmunds W. John , Métras Raphaёlle
Published: May 2022

Background

Crimean-Congo haemorrhagic fever virus (CCHFV) is a highly pathogenic virus for which a safe and effective vaccine is not yet available, despite being considered a priority emerging pathogen. Understanding transmission patterns and the use of potential effective vaccines are central elements of the future plan against this infection.

Methods

We developed a series of models of transmission amongst livestock, and spillover infection into humans. We use real-world human and animal data from a CCHFV endemic area in Afghanistan (Herat) to calibrate our models. We assess the value of environmental drivers as proxy indicators of vector activity, and select the best model using deviance information criteria. Finally we assess the impact of vaccination by simulating campaigns targeted to humans or livestock, and to high-risk subpopulations (i.e, farmers).

Findings

Saturation deficit is the indicator that better explains tick activity trends in Herat. Recent increments in reported CCHFV cases in this area are more likely explained by increased surveillance capacity instead of changes in the background transmission dynamics. Modelling suggests that clinical cases only represent 31% (95% CrI 28%-33%) of total infections in this area. Vaccination campaigns targeting humans would result in a much larger impact than livestock vaccination (266 vs 31 clinical cases averted respectively) and a more efficient option when assessed in courses per case averted (35 vs 431 respectively). Targeted vaccination of farmers is impactful and more efficient, resulting in 19 courses per case averted (95% CrI 7–62) compared to targeting the general population (35 courses 95% CrI 16–107)

Conclusions

CCHFV is endemic in Herat, and transmission cycles are well predicted by environmental drivers like saturation deficit. Vaccinating humans is likely to be more efficient and impactful than animals, and importantly targeted interventions to high risk groups like farmers can offer a more efficient approach to vaccine roll-out.
P2X4 receptors mediate induction of antioxidants, fibrogenic cytokines and ECM transcripts; in presence of replicating HCV in in vitro setting: An insight into role of P2X4 in fibrosis
Authors: Manzoor Sobia , Khalid Madiha , Idrees Muhammad
Published: May 2022

Background & aims

Major HCV infections lead to chronic hepatitis, which results in progressive liver disease including fibrosis, cirrhosis and eventually hepatocellular carcinoma (HCC). P2X4 and P2X7 are most widely distributed receptors on hepatocytes.

Methods

Full length P2X4 (1.7kb) (Rattus norvegicus) was sub cloned in mammalian expression vector pcDNA3.1+. Two stable cell lines 293T/P2X4 (experimental) and 293T/ NV or null vector (control) were established. Both cell lines were inoculated with high viral titers human HCV sera and control human sera. Successfully infected cells harvested on day 5 and day 9 of post infection were used for further studies.

Results

The results revealed a significant increase in gene expression of P2X4 on day 5 and day 9 Post -infection in cells infected with HCV sera compared with cells inoculated with control sera. Quantitative real time PCR analysis revealed that HO-1 was significantly upregulated in presence of P2X4 in HCV infected cells (P2X4/HCV) when compared with control NV/HCV cells. A significant decrease was observed in expression of Cu/ZnSOD in presence of P2X4 in HCV infected cells compared to control NV/HCV cells. However, expression of both antioxidants was observed unaltered in cells harvested on day 9 post infection. Gene expression of angiotensin II significantly increased in HCV infected cells in presence of P2X4 on day 5 and day 9 of post infection when compared with control NV/HCV cells. A significant increase in gene expression of TNF-α and TGF-β was observed in HCV infected cells in presence of P2X4 on day 9 post infection in comparison with control (NV/HCV cells). However, gene expression of adipokine leptin was not affected in both experimental (P2X4/HCV) and control (NV/HCV) groups on day 5 and day 9 of post infection. Extracellular matrix proteins, laminin and elastin genes expression also significantly increased in presence of P2X4 (HCV/P2X4) on day 9 of post-infection compared to control group NV/HCV cells.

Conclusion

In conclusion, these findings constitute the evidence that P2X4 receptors in the presence of HCV play a significant role in the regulation of key antioxidant enzymes (HO-1, Cu/ZnSOD), in the induction of proinflammatory. cytokine (TNF-α), profibrotic cytokine (TGF-β) vasoactive cytokine (angiotensin II). P2X4 also increases the expression of extracellular matrix proteins (laminin and elastin) in the presence of HCV.
Comparative efficacy of Chinese herbal injections for treating severe pneumonia: A protocol for systematic review and Bayesian network meta-analysis of randomized controlled trials
Authors: Xiao Lu , Niu Liqing , Zhang Xuemin , Liu Xuezheng , Liu Xinqiao , Sun Chongxiang , Yang Xiaokun
Published: May 2022

Background

Severe pneumonia (SP) has a high mortality and is responsible for significant healthcare cost. Chinese herbal injections (CHIs) have been widely used in China as a novel and promising treatment option for SP. Therefore, this study will assess and rank the effectiveness of CHIs to provide more sights for the selection of SP treatment.

Method

Seven databases will be searched, including PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Database, and the Chinese Scientific Journal Database (VIP) from their inception up to October, 2021. The literatures screening, data extraction and the quality assessment of included studies will be conducted independently by two reviewers. Then Bayesian network meta-analysis (NMA) will be performed by WinBUGS 14.0 and STATA 14.0 software. Surface under the cumulative ranking curve (SUCRA) probability values will be applied to rank the examined treatments. The risk of bias of each included study will be evaluated using the Revised Cochrane risk-of-bias tool for randomized trials (ROB 2). Publication bias will be reflected by a funnel plot.

Results

The results of this NMA will be disseminated through a peer-reviewed journal publication.

Conclusion

Our study findings maybe reveal which CHI or CHIs will be better in the treatment of SP and provide more therapy strategies for clinical practitioners and patients.

PROSPERO registration number

CRD42021244587.

Strengths and limitations of this study

Bayesian network meta-analysis (NMA) can integrate direct evidence with indirect evidence of severe pneumonia treated by Chinese herbal injections to generate a clinically useful ranking of these regimens.

This NMA will address Chinese herbal injections for SP and its findings may help to provide more sights for selection of SP treatment.

Evidence drawn from an NMA is limited and should be interpreted with caution.

We only included studies in Chinese and English languages, which may increase the publication bias.
Performance analysis of graphene modified asphalt and pavement performance of SMA mixture
Authors: Yong Peng , Tang Jianhua , Zhou Fei , Guo Rui , Yan Jie , Yang Tao
Published: May 2022

The graphene modified asphalt used in this study was prepared based on a highway project in Gansu Province. In this paper, the high temperature rutting resistance, low temperature cracking resistance, and water stability of SMA-13 asphalt mixture with asphalt (AH-70), SBS modified asphalt and graphene rubber composite modified asphalt were tested and analyzed comparatively by the rutting test, Schellenberg binder drainage test, Cantabro test, freeze-thaw splitting test, and beam bending test. The results showed that the graphene modifier improved the asphalt’s ductility and softening point significantly, and 0.4g graphene content was the threshold and its corresponding mixture performance index. In the other tests under the same conditions, the high temperature and water stability of SMA-13 mixtures of graphene rubber modified asphalt were the best, followed by SBS modified asphalt mixture, and matrix asphalt mixture. Compared with wood fiber, graphene modifier had no significant effect on SMA-13 mixtures’ low temperature performance. The use of graphene modifiers can enhance the adhesion between asphalt and aggregate and its asphalt has good consistency and viscosity. When compared with matrix asphalt and SBS modified SMA-13 mixtures, the water and high temperature stability of graphene modified asphalt mixture is better.
A spatial interaction incorporated betweenness centrality measure
Authors: Wu Xiaohuan , Cao Wenpu , Wang Jianying , Zhang Yi , Yang Weijun , Liu Yu
Published: May 2022

Betweenness centrality (BC) is widely used to identify critical nodes in a network by exploring the ability of all nodes to act as intermediaries for information exchange. However, one of its assumptions, i.e., the contributions of all shortest paths are equal, is inconsistent with variations in spatial interactions along these paths and has been questioned when applied to spatial networks. Hence, this paper proposes a spatial interaction incorporated betweenness centrality (SIBC) for spatial networks. SIBC weights the shortest path between each node pair according to the intensity of spatial interaction between them, emphasizing the combination of a network structure and spatial interactions. To test the rationality and validity of SIBC in identifying critical nodes and edges, two specific forms of SIBC are applied to the Shenzhen street network and China’s intercity network. The results demonstrate that SIBC is more significant than BC when we also focus on the network functionality rather than only on the network structure. Moreover, the good performance of SIBC in robustness analysis illustrates its application value in improving network efficiency. This study highlights the meaning of introducing spatial configuration into empirical models of complex networks.
“You see this thing is hard… ey, this thing is painful”: The burden of the provider role and construction of masculinities amongst Black male mineworkers in Marikana, South Africa
Authors: Sikweyiya Yandisa , Nkosi Sebenzile , Langa Malose , Operario Don , Lurie Mark N.
Published: May 2022

In this paper we examine men’s insights on how migration and minework affect their perceptions and performances of masculinity in the settings of minework and in their “real home” communities and explore the potential consequences of masculinity constructions for their own and their family’s health. This study used qualitative methodology. Findings are based on 13 in-depth interviews conducted over two phases of data collection with adult men who were either working or seeking work in the mines in North-West province, South Africa. Data suggest that for these men, migration to and working in the mines meant they must straddle the temporal space of work and the rural home space. For these men, the role of provider was an inescapable demand and, resulting from migration for work, their experience of fatherhood was solely centred on material provision with little or no emotional involvement with their children. Findings further illustrate the impact of minework on men’s health and livelihoods-resulting in some men reimagining and seeking to create alternative career paths for their children. There is pressing need for labour reforms on the employment conditions of low-paid mine workers to enable them to reinforce their livelihoods and secure better futures for their families. Gender-transformative interventions which aim to transform ideas of masculinity that emphasize providing rather than emotional involvement with children are also needed.
Automatic reagent handling and assay processing of human biospecimens inside a transportation container for a medical disaster response against radiation
Authors: Akkad Adam R. , Gu Jian , Duane Brett , Norquist Alan , Brenner David J. , Ramakumar Adarsh , Zenhausern Frederic
Published: May 2022

Biological materials can be shipped off-site for diagnostic, therapeutic and research purposes. They usually are kept in certain environments for their final application during transportation. However, active reagent handling during transportation from a collection site to a laboratory or biorepository has not been reported yet. In this paper, we show the application of a micro-controlled centrifugal microfluidic system inside a shipping container that can add reagent to an actively cultured human blood sample during transportation to ensure a rapid biodosimetry of cytokinesis-block micronucleus (CBMN) assay. The newly demonstrated concept could have a significant impact on rapid biodosimetry triage for medical countermeasure in a radiological disaster. It also opens a new capability in accelerated sample processing during transportation for biomedical and healthcare applications.
Symptoms of psychological distress amongst women during the COVID-19 pandemic in Saudi Arabia
Authors: Qattan Ameerah M. N.
Published: May 2022

Background

Since the emergence of the COVID-19 pandemic in early 2020, several countries are still struggling to contain its spread. Apart from economic challenges, the pandemic has had a negative impact on the mental health and psychological well-being of millions of people worldwide. The effects of COVID-19 are disproportionate depending on sociodemographic characteristics. The aim of this study was to investigate the impact of COVID-19 on psychological distress among women in Saudi Arabia.

Methods

Data were extracted from an online cross-sectional self-reported questionnaire conducted to measure symptoms of psychological distress during the COVID-19 pandemic in Saudi Arabia from 3 May to 8 May 2020. The study included a sample of 1527 women. The questionnaire was based on the COVID-19 Peritraumatic Distress Index (CPDI) tool to categorise women who responded to the questionnaire as experiencing normal, mild, or severe levels of distress. Sociodemographic factors related to different levels of psychological distress among women were examined using descriptive analysis and multinomial logistic regression models.

Results

Overall, 44% of the respondents indicated symptoms of psychological distress due to the COVID-19 pandemic. Approximately 36% of women showed symptoms of mild psychological distress, with 8% of women experiencing a severe distress level. The results also revealed particularly high levels of psychological distress among younger women and female healthcare workers.

Conclusion

The COVID-19 pandemic highly contributes to psychological distress among women in Saudi Arabia. Therefore, it is essential to establish medium- and long-term strategies that target the most vulnerable women affected by the COVID-19 pandemic.
Resting heart rate and incident atrial fibrillation: A stratified Mendelian randomization in the AFGen consortium
Authors: Siland J. E. , Geelhoed B. , Roselli C. , Wang B. , Lin H. J. , Weiss S. , Trompet S. , van den Berg M. E. , Soliman E. Z. , Chen L. Y. , Ford I. , Jukema J. W. , Macfarlane P. W. , Kornej J. , Lin H. , Lunetta K. L. , Kavousi M. , Kors J. A. , Ikram M. A. , Guo X. , Yao J. , Dörr M. , Felix S. B. , Völker U. , Sotoodehnia N. , Arking D. E. , Stricker B. H. , Heckbert S. R. , Lubitz S. A. , Benjamin E. J. , Alonso A. , Ellinor P. T. , van der Harst P. , Rienstra M.
Published: May 2022

Background

Both elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genetically-determined resting heart rate and incident AF.

Method and results

Seven cohorts of the AFGen consortium contributed data to this meta-analysis. All participants were of European ancestry with known AF status, genotype information, and a heart rate measurement from a baseline electrocardiogram (ECG). Three strata of instrumental variable-free resting heart rate were used to assess possible non-linear associations between genetically-determined resting heart rate and the logarithm of the incident AF hazard rate: <65; 65–75; and >75 beats per minute (bpm). Mendelian randomization analyses using a weighted resting heart rate polygenic risk score were performed for each stratum.

We studied 38,981 individuals (mean age 59±10 years, 54% women) with a mean resting heart rate of 67±11 bpm. During a mean follow-up of 13±5 years, 4,779 (12%) individuals developed AF. A U-shaped association between the resting heart rate and the incident AF-hazard ratio was observed. Genetically-determined resting heart rate was inversely associated with incident AF for instrumental variable-free resting heart rates below 65 bpm (hazard ratio for genetically-determined resting heart rate, 0.96; 95% confidence interval, 0.94–0.99; p = 0.01). Genetically-determined resting heart rate was not associated with incident AF in the other two strata.

Conclusions

For resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.
Impact of Sporisorium scitamineum infection on the qualitative traits of commercial cultivars and advanced lines of sugarcane
Authors: Rajput Muhammad Aslam , Syed Rehana Naz , Khoso Fahad Nazir , Hajano Jamal-U-Din , Rajput Nasir Ahmed , Khanzada Muhammad Ali , Lodhi Abdul Mubeen
Published: May 2022

Whip smut disease of sugarcane, caused bySporisorium scitamineum, is considered one of the main constraints in the successful cultivation of sugarcane. The pathogen infection can decrease the quantity and quality of the produce. Cultivation of resistant varieties is the most feasible strategy to combat the harms of this devastating disease. Development of varieties having disease-resistance together with improved important traits such as brix, pol, purity, CSS, and low fiber contents are desirable. Therefore, we documented the variances in quality traits of 104 sugarcane cultivars under disease pressure in split-plot design with 6 replications. The split ANOVA revealed a highly significant impact (p<0.0001) between treatments (inoculated and uninoculated), within cultivars as well as interaction ‘Cultivars x Treatments’ effect on brix, pol, fiber, purity, and CSS contents. In inoculated plots, the infection ofS.scitamineumbrought a highly significant reduction (t>4.032) in brix, pol, purity, and CSS of more than 40% of the cultivars used, as compared to the uninoculated ones. On the other hand, the smut infection caused a highly significant (t>4.032) increase in fiber percentage of 41 cultivars. We found significant positive correlations between smut rating and reduction of brix, pol, purity, and CSS contents. The cultivars that were caught with greater disease severity, compromised a higher reduction of their useful contents. Similarly, a significant positive correlation was found between increased fiber percent and smut rating. Remarkably, cultivars that showed immune reactions to whip smut disease were not statistically different from uninoculated ones in brix, pol, purity, CSS, and fiber contents. Variable effects of whip smut infection to quality parameters of different cultivars depict the importance of further improvement through breeding programs.
Islet autoantibody positivity in an adult population with recently diagnosed diabetes in Uganda
Authors: Kibirige Davis , Sekitoleko Isaac , Balungi Priscilla , Kyosiimire-Lugemwa Jacqueline , Lumu William , Jones Angus G. , Hattersley Andrew T. , Smeeth Liam , Nyirenda Moffat J.
Published: May 2022

Aims

This study aimed to investigate the frequency of islet autoantibody positivity in adult patients with recently diagnosed diabetes in Uganda and its associated characteristics.

Methods

Autoantibodies to glutamic acid decarboxylase-65 (GADA), zinc transporter 8 (ZnT8-A), and tyrosine phosphatase (IA-2A) were measured in 534 adult patients with recently diagnosed diabetes. Islet autoantibody positivity was defined based on diagnostic thresholds derived from a local adult population without diabetes. The socio-demographic, clinical, and metabolic characteristics of islet autoantibody-positive and negative participants were then compared. The differences in these characteristics were analysed using the x2 test for categorical data and the Kruskal Wallis test for continuous data. Multivariate analysis was performed to identify predictors of islet autoantibody positivity.

Results

Thirty four (6.4%) participants were positive for ≥1 islet autoantibody. GADA, IA-2A and ZnT8-A positivity was detected in 17 (3.2%), 10 (1.9%), and 7 (1.3%) participants, respectively. Compared with those negative for islet autoantibodies, participants positive for islet autoantibodies were more likely to live in a rural area (n = 18, 52.9% Vs n = 127, 25.5%, p = 0.005), to be initiated on insulin therapy (n = 19, 55.9% Vs n = 134, 26.8%, p<0.001), to have a lower median waist circumference (90 [80–99] cm Vs 96 [87–104.8], p = 0.04), waist circumference: height ratio (0.55 [0.50–0.63] vs 0.59 [0.53–0.65], p = 0.03), and fasting C-peptide concentration (0.9 [0.6–1.8] Vs 1.4 [0.8–2.1] ng/ml, p = 0.01). On multivariate analysis, living in a rural area (odds ratio or OR 3.62, 95%CI 1.68–7.80, p = 0.001) and being initiated on insulin therapy (OR 3.61, 95% CI 1.67–7.83, p = 0.001) were associated with islet autoantibody positivity.

Conclusion

The prevalence of islet autoantibody positivity was relatively low, suggesting that pancreatic autoimmunity is a rare cause of new-onset diabetes in this adult Ugandan population. Living in a rural area and being initiated on insulin therapy were independently associated with islet autoantibody positivity in this study population.
Expression profiles of miR3181 and miR199a in plasma and placenta of virally suppressed HIV-1 infected Cameroonian pregnant women at delivery
Authors: Esemu Livo F. , Awanakam Honore , Nanfa Dieudonne , Besong Michael , Tsayem Idriss , Nkenfou Celine Nguefeu , Bigoga Jude , Leke Rose , Eugene Sobngwi , Ndhlovu Lishomwa C. , Loni Gabriel Ekali
Published: May 2022

Human immunodeficiency virus (HIV)-1 infection during pregnancy reduces the transplacental transfer of protective maternal antibodies needed to confer immunity during early postnatal life. However, the mediation of MicroRNA in this dysregulation is not well understood MicroRNAs 3181 and 199a have been shown to mediate neonatal Fc receptor (FcRn)-like transmembrane antibody transfer and endocytosis respectively but their expression levels in the placenta and plasma in women living with HIV have not been extensively investigated. The objective of this study was to determine how the expression levels of miR-3181 and miR-199a in the placenta and plasma are affected in women chronically infected with HIV who are on antiretroviral therapy (ART) and are virally suppressed at delivery. In this pilot case-control study, plasma and placenta biopsies were obtained from 36 (18 HIV+ and 18 HIV-) Cameroonian women at delivery. MicroRNAs 3181 and 199a expression levels were measured using RT-qPCR, data was analyzed using SPSS22.0 and R 3.60, and p values below 0.05 were considered statistically significant. All the HIV-infected women were on known ART regimens and were virally suppressed. There was no significant difference in the levels of miR-3181 (p>0.05) in the placenta and plasma amongst HIV-infected and HIV uninfected women. The expression levels of miR-199a were significantly greater in the plasma compared to the placenta of HIV+ (p = 0.00005) and HIV- (p = 0.027) women. Moreover, there was a significantly higher (p = 0.02) level of miR-199a in the plasma of women with HIV and their uninfected counterparts. Linear regression models adjusted for systolic pressure showed no significant difference (p>0.05) in the levels of miR-199a and miR-3181 in both the placenta and plasma due to HIV infection. Our findings suggest that even though ART uptake and viral suppression might help in maintaining miR3181 and miR199a levels in the placenta of women with HIV at comparative levels to those of their HIV negative counterparts, the significantly higher levels of miR-199a in the plasma of women with HIV compared to the placenta might highlight lurking systemic dangers and requires further investigation.
Effects of arsenic on the topology and solubility of promyelocytic leukemia (PML)-nuclear bodies
Authors: Hirano Seishiro , Udagawa Osamu
Published: May 2022

Promyelocytic leukemia (PML) proteins are involved in the pathogenesis of acute promyelocytic leukemia (APL). Trivalent arsenic (As3+) is known to cure APL by binding to cysteine residues of PML and enhance the degradation of PML-retinoic acid receptor α (RARα), a t(15;17) gene translocation product in APL cells, and restore PML-nuclear bodies (NBs). The size, number, and shape of PML-NBs vary among cell types and during cell division. However, topological changes of PML-NBs in As3+-exposed cells have not been well-documented. We report that As3+-induced solubility shift underlies rapid SUMOylation of PML and late agglomeration of PML-NBs. Most PML-NBs were toroidal and granular dot-like in GFPPML-transduced CHO-K1 and HEK293 cells, respectively. Exposure to As3+ and antimony (Sb3+) greatly reduced the solubility of PML and enhanced SUMOylation within 2 h in the absence of changes in the number and size of PML-NBs. However, the prolonged exposure to As3+ and Sb3+ resulted in agglomeration of PML-NBs. Exposure to bismuth (Bi3+), another Group 15 element, did not induce any of these changes. ML792, a SUMO activation inhibitor, reduced the number of PML-NBs and increased the size of the NBs, but had little effect on the As3+-induced solubility change of PML. These results warrant the importance of As3+- or Sb3+-induced solubility shift of PML for the regulation intranuclear dynamics of PML-NBs.
Risk of chronic pancreatitis in carriers of loss-of-function CTRC variants: A meta-analysis
Authors: Takáts Amanda , Berke Gergő , Gede Noémi , Németh Balázs Csaba , Witt Heiko , Głuszek Stanisław , Rygiel Agnieszka Magdalena , Hegyi Péter , Sahin-Tóth Miklós , Hegyi Eszter
Published: May 2022

The digestive protease chymotrypsin C (CTRC) protects the pancreas against pancreatitis by degrading potentially harmful trypsinogen. Loss-of-function genetic variants in CTRC increase risk for chronic pancreatitis (CP) with variable effect size, as judged by the reported odds ratio (OR) values. Here, we performed a meta-analysis of published studies on four variants that alter the CTRC amino-acid sequence, are clinically relatively common (global carrier frequency in CP >1%), reproducibly showed association with CP and their loss of function phenotype was verified experimentally. We found strong enrichment of CTRC variants p.A73T, p.V235I, p.K247_R254del, and p.R245W in CP cases versus controls, yielding OR values of 6.5 (95% confidence interval (CI) 2.4–17.8), 4.5 (CI 2.2–9.1), 5.4 (CI 2.6–11.0), and 2.6 (CI 1.6–4.2), respectively. Subgroup analysis demonstrated disease association of variants p.K247_R254del and p.R245W in alcoholic CP with similar effect sizes as seen in the overall CP group. Homozygosity or compound heterozygosity were rare and seemed to be associated with higher risk. We also identified a so far unreported linkage disequilibrium between variant p.K247_R254del and the common c.180C>T (p.G60 =) haplotype. Taken together, the results indicate that heterozygous loss-of-function CTRC variants increase the risk for CP approximately 3-7-fold. This meta-analysis confirms the clinical significance of CTRC variants and provides further justification for the genetic screening of CP patients.
Graduate students locked down? PhD students’ satisfaction with supervision during the first and second COVID-19 lockdown in Belgium
Authors: van Tienoven Theun Pieter , Glorieux Anaïs , Minnen Joeri , te Braak Petrus , Spruyt Bram
Published: May 2022

Background

Supervisor support is crucial for the successful and timely completion of the PhD and the largest contributor to PhD students’ overall job satisfaction. The COVID-19 pandemic affected PhD students’ life substantially through delayed experiments, missed timelines, running out of funding, change to online team- and supervisor meetings, mandatory working from home, and social confinement.

Aim

This contribution considers PhD students’ satisfaction scores to reflect the extent to which PhD students felt supported by their supervisor during the COVID-19 pandemic so far and aims to investigate to what extent did PhD students’ satisfaction with supervisor support changed over time.

Method

It uses two longitudinal two cohorts of wave 4 to 5 of the PhD Survey at a Belgian university. These cohorts are representative of two different ways the COVID-19 pandemic might have impacted doctoral research. Cohort 1 (n = 345) includes a pre-COVID measurement (April-May 2019) and a measurement immediately after the start of the abrupt lockdown in April-May 2020. Cohort 2 (n = 349) includes the measurement at the onset of the pandemic in 2020 and after a year with continuously changing containment policies (April-May 2021). The composite measure of satisfaction with supervisor support is based on six items with high internal consistency.

Results

No significant net effect of time was revealed. Instead within subject interactions with time showed that in cohort 1, PhD students at the start of their PhD trajectory and PhD students with family responsibilities reported lower supervisor satisfaction scores over time. In cohort 2, PhD students not pursuing academic careers reported lower satisfaction scores over time.

Conclusion

In times of crises, special attention needs to be paid to PhD students who are extra susceptible to uncertainties because of their junior status or personal situation, and especially those PhD students for whom doctoral research is not a trajectory to position themselves in academia.
Plasma antibodies from humans infected with zoonotic simian foamy virus do not inhibit cell-to-cell transmission of the virus despite binding to the surface of infected cells
Authors: Couteaudier Mathilde , Montange Thomas , Njouom Richard , Bilounga-Ndongo Chanceline , Gessain Antoine , Buseyne Florence
Published: May 2022

Zoonotic simian foamy viruses (SFV) establish lifelong infection in their human hosts. Despite repeated transmission of SFV from nonhuman primates to humans, neither transmission between human hosts nor severe clinical manifestations have been reported. We aim to study the immune responses elicited by chronic infection with this retrovirus and previously reported that SFV-infected individuals generate potent neutralizing antibodies that block cell infection by viral particles. Here, we assessed whether human plasma antibodies block SFV cell-to-cell transmission and present the first description of cell-to-cell spreading of zoonotic gorilla SFV. We set-up a microtitration assay to quantify the ability of plasma samples from 20 Central African individuals infected with gorilla SFV and 9 uninfected controls to block cell-associated transmission of zoonotic gorilla SFV strains. We used flow-based cell cytometry and fluorescence microscopy to study envelope protein (Env) localization and the capacity of plasma antibodies to bind to infected cells. We visualized the cell-to-cell spread of SFV by real-time live imaging of a GFP-expressing prototype foamy virus (CI-PFV) strain. None of the samples neutralized cell-associated SFV infection, despite the inhibition of cell-free virus. We detected gorilla SFV Env in the perinuclear region, cytoplasmic vesicles and at the cell surface. We found that plasma antibodies bind to Env located at the surface of cells infected with primary gorilla SFV strains. Extracellular labeling of SFV proteins by human plasma samples showed patchy staining at the base of the cell and dense continuous staining at the cell apex, as well as staining in the intercellular connections that formed when previously connected cells separated from each other. In conclusion, SFV-specific antibodies from infected humans do not block cell-to-cell transmission, at leastin vitro, despite their capacity to bind to the surface of infected cells.

Trial registration: Clinical trial registration:www.clinicaltrials.gov,https://clinicaltrials.gov/ct2/show/NCT03225794/.
Isaac Anderson
Authors: Jackson Alicia K.
Published: May 2022

The Black Church grows from its beginnings in brush arbors and slave missions, and Methodist slave owners rush to train Black religious leaders in Methodism in order to maintain control over enslaved people. Isaac H. Anderson becomes one such leader and the slave of William Jackson Anderson, a wealthy Merchant Prince of Fort Valley. Both White and Black Methodists vie for influence of Southern, rural Blacks.
1870
Authors: Jackson Alicia K.
Published: May 2022

Black churches serve prominently as a refuge for Black Georgians as they deal with the trauma of slavery, injustice, and violence after Emancipation. Frustrated by the lack of support from white Southern Methodist leaders and by intra-racial conflicts, Isaac Anderson and other Black Methodist leaders found the Colored Methodist Episcopal Church, and its formation is integral to his election to the Georgia legislature. White Southern Methodists express concern over prominent AME Church leaders like Henry M. Turner and Tunis Campbell Sr., who are also ministers and politicians, and this concern leads Southern Methodist leaders to reluctantly accept Anderson’s political activity fearing Turner and Campbell’s influence in Georgia politics among Black Methodists.