bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Bud3 domains sufficient for bud neck targeting in S. cerevisiae
Authors: Schrock Madison N. , Yan Yao , Goeckel Megan E. , Basgall Erianna M. , Lewis Isabel C. , Leonard Katherine G. , Halloran Megan , Finnigan Gregory C.
Published: March 2022

The cytoskeleton serves a diverse set of functions in both multi- and unicellular organisms, including movement, transport, morphology, cell division and cell signalling. The septin family of cytoskeletal proteins are found within all fungi and metazoans and can generate three-dimensional scaffolds in vivo that promote membrane curvature, serve as physical barriers and coordinate cell cycle checkpoints. In budding yeast, the septins organize into polymerized filaments that decorate the division site between mother and daughter cells during mitosis; assembly of this structure at the ‘bud neck’ is critical for completion of cytokinesis and execution of numerous other cellular events. One such pathway includes bud site selection and the recruitment of proteins such as Bud4 and Bud3 that are responsible for promoting an axial budding pattern in haploid yeast. While Bud4 appears to be recruited to the septins independently of the presence of Bud3, it is likely that Bud3 can localize to the bud neck using both Bud4-dependent and Bud4-independent mechanisms. Furthermore, it remains unclear which precise domain or domains within Bud3 is/are both necessary and sufficient for optimal association at the septin structure. In this study, we examined the localization of GFP-Bud3 constructs in otherwise wild-type (WT) haploid yeast cells expressing Cdc10-mCherry using fluorescence microscopy; we tested a collection of N- and C-terminal truncations and fusions of separate Bud3 protein elements to identify the smallest domain(s) responsible for bud neck localization. We found that the coordinate action of the central amphipathic helix (residues 847–865) and a partially conserved C-terminal motif (residues 1172–1273) was sufficient to promote bud neck recruitment in the presence of endogenous Bud3. This domain is considerably smaller than the previously characterized C-terminal portion required to physically interact with Bud4 (1221–1636) and utilizes a similar mechanism of pairing membrane association, with a separate localization domain, similar to other non-septin proteins targeted to the division site during cell division.
Paenibacillus farraposensis sp. nov., isolated from a root nodule of Arachis villosa
Authors: Roldán Diego M. , Costa Andrés , Králová Stanislava , Busse Hans-Jürgen , Amarelle Vanesa , Fabiano Elena , Menes Rodolfo Javier
Published: March 2022

Strain UY79Twas isolated from a root nodule ofArachis villosa, collected at the Esteros de Farrapos National Park, Río Negro, Uruguay. Cells were non-motile Gram-variable rods with central to subterminal oval to ellipsoidal endospores that swell the sporangia. Growth was observed in the range of 15–42 °C (optimum, 30 °C), pH 5.0–9.0 (optimum, pH 7.0–8.0) and with up to 3 % (w/v) NaCl (optimum, 1–2 %). Strain UY79Twas facultative anaerobic, catalase-positive and oxidase-negative. According to the results of 16S rRNA gene sequence analysis, UY79Tbelongs to the genusPaenibacillusand is closely related toP. ottowiiMS2379T,P. peoriaeBD-57T,P. polymyxaATCC 842TandP. brasilensisPB172T, exhibiting 99.4, 99.0, 99.0 and 98.9% sequence identity, respectively. Average nucleotide identity and digital DNA–DNA hybridization values with the most closely related type strains were 74.3–88.6% and 38.2–48.7 %, respectively. Major fatty acids (>10 %) were anteiso-C15:0, iso-C15:0,and C16 : 0. Menaquinones MK-7 and MK-6 were the only isoprenoid quinones detected. Major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified glycolipid. Spermidine was the predominant polyamine. The DNA G+C content based on the draft genome sequence was 46.34 mol%. Based on the current polyphasic study, UY79Trepresents a novel species of the genusPaenibacillus, for which the namePaenibacillus farraposensissp. nov. is proposed. The type strain is UY79T(=CCM 9147T=CGMCC 1.19038T).
Contribution of the efflux pump AcrAB-TolC to the tolerance of chlorhexidine and other biocides in Klebsiella spp.
Authors: Wand Matthew E. , Darby Elizabeth M. , Blair Jessica M. A. , Sutton J. Mark
Published: March 2022

Introduction. We are becoming increasingly reliant on the effectiveness of biocides to combat the spread of Gram-negative multi-drug-resistant (MDR) pathogens, including

Klebsiella pneumoniae

. It has been shown that chlorhexidine exposure can lead to mutations in the efflux pump repressor regulators SmvR and RamR, but the contribution of each individual efflux pump to biocide tolerance is unknown.

Hypothesis. Multiple efflux pumps, including SmvA and AcrAB-TolC, are involved in increased tolerance to biocides. However, strains with upregulated AcrAB-TolC caused by biocide exposure are more problematic due to their increased MDR phenotype.

Aim. To investigate the role of AcrAB-TolC in the tolerance to several biocides, including chlorhexidine, and the potential threat of cross-resistance to antibiotics through increased expression of this efflux pump.

Methodology. Antimicrobial susceptibility testing was performed on

K. pneumoniae

isolates with ramR mutations selected for after exposure to chlorhexidine, as well as transposon mutants in components and regulators of AcrAB-TolC. RTPCR was used to detect the expression levels of this pump after biocide exposure. Strains from the globally important ST258 clade were compared for genetic differences in acrAB-TolC and its regulators and for phenotypic differences in antimicrobial susceptibility.

Results. Cross-resistance to antimicrobials was observed following mutations in ramR. Exposure to chlorhexidine led to increased expression of acrA and its activator ramA, and transposon mutants in AcrAB-TolC have increased susceptibility to several biocides, including chlorhexidine. Variations in ramR within the ST258 clade led to an increase in tolerance to certain biocides, although this was strain dependent. One strain, MKP103, that had increased levels of biocide tolerance showed a unique mutation in ramR that was reflected in enhanced expression of acrA and ramA. MKP103 transposon variants were able to further enhance their tolerance to specific biocides with mutations affecting SmvA.

Conclusions. Biocide tolerance in

K. pneumoniae

is dependent upon several components, with increased efflux through AcrAB-TolC being an important one.
Existential suffering as a motive for assisted suicide: difficulties, acceptability, management and roles from the perspectives of Swiss professionals
Authors: Gaignard Marie-Estelle , Pautex Sophie , Hurst Samia
Published: March 2022

Background

Existential suffering is often a part of the requests for assisted suicide (AS). Its definitions have gained in clarity recently and refer to a distress arising from an inner realization that life has lost its meaning. There is however a lack of consensus on how to manage existential suffering, especially in a country where AS is legal and little is known about the difficulties faced by professionals confronted with these situations.

Objectives

To explore the perspectives of Swiss professionals involved in end-of-life care and assisted suicide on the management of existential suffering when it is part of AS requests, taking into account the question of roles, as well as on the difficulties they encounter along the way and their views on the acceptability of existential suffering as a motive for AS.

Methods

A qualitative study based on face-to-face interviews was performed among twenty-six participants from the fields of palliative and primary care as well as from EXIT right-to-die organization. A semi-structured interview guide exploring four themes was used. Elements from the grounded theory approach were applied.

Results

Almost all participants reported experiencing difficulties when facing existential suffering. Two-thirds considered existential suffering as a justifiable reason for requesting AS. Concerning the management of existential suffering, participants referred to the notion of being present, respect, explore the suffering, give meaning, working together, psychological support, spiritual support, relieve physical symptoms and palliative sedation.

Conclusion

This study offers a unique opportunity to reflect on what are desirable responses to existential suffering when it is part of AS requests. Existential suffering is plural and certainly implies a multiplicity of responses as well. These situations remain however difficult and controversial according to Swiss professionals. Clinicians’ education should better address these issues and give them the tool to take care of patients with existential suffering.
White Adipose Tissue Compositional and Transcriptional Patterns with Progressive Glucose Intolerance in Persons with HIV
Authors: Bailin Samuel S. , Kropski Jonathan A. , Gangula Rama D. , Hannah LaToya , Simmons Joshua D. , Mashayekhi Mona , Ye Fei , Fan Run , Mallal Simon , Warren Christian M. , Kalams Spyros A. , Gabriel Curtis L. , Wanjalla Celestine N. , Koethe John R.
Published: March 2022

Subcutaneous adipose tissue (SAT) is a critical regulator of systemic metabolic homeostasis. Persons with HIV (PWH) have an increased risk of metabolic diseases and significant alterations in the SAT immune environment compared with the general population. We generated a comprehensive SAT atlas to characterize cellular compositional and transcriptional changes in 59 PWH with a spectrum of metabolic health. Glucose intolerance was associated with increased lipid-associated macrophages and CD4+and CD8+T effector memory cells, and decreased perivascular macrophages. We observed a coordinated intercellular regulatory program which enriched for genes related to inflammation and lipid-processing across multiple cell types as glucose intolerance increased. Increased CD4+effector memory tissue resident cells most strongly associated with altered expression of adipocyte genes critical for lipid metabolism and cellular regulation. Many of these findings were present in a separate group of 32 diabetic HIV-negative persons, suggesting these changes are not specific to HIV.
Association of seminal polyaromatic hydrocarbons exposome with idiopathic male factor infertility: A proteomic insight into sperm function
Authors: Nayak Jasmine , Jena Soumya Ranjan , Kumar Sugandh , Kar Sujata , Dixit Anshuman , Samanta Luna
Published: March 2022

Oxidative stress (OS) is implicated in 80% of idiopathic male infertility (IMI) patients where exposure to redox active environmental toxicants such as polyaromatic hydrocarbons (PAHs) may play. In the present study the seminal exposome of various PAH was analyzed in two separate cohorts including 43 fertile donors and 60 IMI patients by HPLC and receiver operator characteristic curve was applied to find out the cut-off limits. Furthermore, spermatozoa from both the groups were subjected to label free liquid chromatography mass spectroscopy (LC-MS/MS) followed by bioinformatics analysis to elucidate the molecular mechanism(s) involved and the key proteins from the affected pathways were validated by western blot along with oxidative modification of proteins. Of the 16 standard PAH 13 were detected in the semen. Receiver Operator Character (ROC) Curve analysis (AUCROC) revealed the PAHs having most significant effect on fertility are of the following order Anthracene<benzo(a)pyrene<benzo[b]fluoranthene<Fluoranthene<benzo(a)anthracene<indol (123CD)pyrene<pyrene<naphthalene<dibenzo(AH)anthracene<fluorene<2bromonaphthalene <chrysene<benzo(GH1)perylene. Benzo[a] pyrene is invariably present in all infertile patients while naphthalene is present in both fertile and IMI group. Of the total 773 detected proteins (Control: 631 and PAH: 717); 71 were differentially expressed (13 underexpressed, 58 overexpressed) in IMI patients resulting in impaired mitochondrial dysfunction and oxidative phosphorylation, DNA damage, Aryl hydrocarbon receptor (AHR) signalling, xenobiotic metabolism and induction of NRF-2 mediated oxidative stress response (increased in 4-hydroxynonenal and nitrosylated protein adduct formation, and declined antioxidant defence). The increased GSH/GSSG ratio in patients may be an adaptive response to metabolize the xenobiotics via conjugation as evidenced by overexpression of AHR and Heat shock protein 90 beta (HSP90β) in patients. Seminal PAH concentrations, oxidative protein modification along with protein markers (e.g. AHR and HSP90β) may help in better prediction and management of IMI. Contribution of environment borne PAH in semen should not undermined in infertility evaluation.
Oscillatory dynamics underlying emotion-cognition integration: differential role of theta and alpha oscillations
Authors: Wang Zhihao , Goerlich Katharina S. , Chen Mai , Xu Pengfei , Luo Yuejia , Aleman André
Published: March 2022

A fundamental aspect of human mental life is the seamless ability for integration of emotion and cognition. Despite progress regarding the spatial architecture of Emotion-Cognition Integration (ECI), the time course of ECI processes remains unclear. To examine the temporal organization of brain oscillations underpinning ECI, we simultaneously manipulated emotional valence of stimuli and cognitive task demand while recording electrophysiological responses of 61 participants. They were asked to complete tasks with low (body-part judgement) and high (laterality judgement) cognitive demand while viewing other people photographs that varied on dimensions of laterality (left or right), body-part (hand or foot), and emotional valence (pain or no pain). We found increased reaction times and error rates in pain versus no pain during laterality judgement relative to body-part judgement, suggesting reciprocal inhibition between emotion and cognition. EEG results showed that 1) emotion processing (valence) occurred first in the theta band from 144 to 372 ms; 2) cognitive processing (laterality) took place in the theta band from 332 to 608 ms; 3) emotional and cognitive processes were integrated in the alpha band from 268 ms and lasted to 800 ms. These findings reveal oscillatory dynamics of the processing and integration of emotion and cognition, providing further insights into the underlying neurophysiology. This may ultimately contribute to our understanding of ECI processing in psychopathology.
Kiawah and Seabrook islands are a critical site for therufaRed Knot (Calidris canutus rufa)
Authors: Pelton Mary Margaret , Padula Sara R. , Garcia-Walther Julian , Andrews Mark , Mercer Robert , Porter Ron , Sanders Felicia , Thibault Janet , Senner Nathan R. , Linscott Jennifer A.
Published: March 2022

TherufaRed Knot (Calidris canutus rufa) is a migratory shorebird that performs one of the longest known migrations of any bird species — from their breeding grounds in the Canadian Arctic to their nonbreeding grounds as far south as Tierra del Fuego — and has experienced a population decline of over 85% in recent decades. During migration, knots rest and refuel at stopover sites along the Atlantic Coast, including Kiawah and Seabrook islands in South Carolina. Here, we document the importance of Kiawah and Seabrook islands for knots by providing population and stopover estimates during their spring migration. We conducted on-the-ground surveys between 19 February - 20 May 2021 to record the occurrence of individually marked knots. In addition, we quantified the ratio of marked to unmarked knots and deployed geolocators on knots captured in the area. Using a superpopulation model, we estimated a minimum passage population of 17,247 knots (~41% of the totalrufaknot population) and an average stopover duration of 47 days. Our geolocator results also showed that knots using Kiawah and Seabrook islands can bypass Delaware Bay and fly directly to the Canadian Arctic. Finally, our geolocators, combined with resighting data from across the Atlantic Flyway, indicate that a large network of more than 70 coastal sites mostly concentrated along the coasts of Florida, Georgia, South Carolina, and North Carolina provide stopover and overwintering habitat for the knots we observed on Kiawah and Seabrook islands. These findings corroborate that Kiawah and Seabrook islands should be recognized as critical sites in the knot network and, therefore, a conservation priority. As a result, the threats facing the sites — such as prey management issues, anthropogenic disturbance, and sea level rise — require immediate attention.
Gene expression noise accelerates the evolution of a biological oscillator
Authors: Lin Yen Ting , Buchler Nicolas E.
Published: March 2022

Gene expression is a biochemical process, where stochastic binding and unbinding events naturally generate fluctuations and cell-to-cell variability in gene dynamics. These fluctuations typically have destructive consequences for proper biological dynamics and function (e.g., loss of timing and synchrony in biological oscillators). Here, we show that gene expression noise counter-intuitively accelerates the evolution of a biological oscillator and, thus, can impart a benefit to living organisms. We used computer simulations to evolve two mechanistic models of a biological oscillator at different levels of gene expression noise. We first show that gene expression noise induces oscillatory-like dynamics in regions of parameter space that cannot oscillate in the absence of noise. We then demonstrate that these noise-induced oscillations generate a fitness landscape whose gradient robustly and quickly guides evolution by mutation towards robust and self-sustaining oscillation. These results suggest that noise can help dynamical systems evolve or learn new behavior by revealing cryptic dynamic phenotypes outside the bifurcation point.

Graphical Abstract
Cross-trait assortative mating is widespread and inflates genetic correlation estimates
Authors: Border Richard , Athanasiadis Georgios , Buil Alfonso , Schork Andrew , Cai Na , Young Alexander , Werge Thomas , Flint Jonathan , Kendler Kenneth , Sankararaman Sriram , Dahl Andy , Zaitlen Noah
Published: March 2022

The observation of genetic correlations between disparate traits has been interpreted as evidence of widespread pleiotropy, altered theories of human genetic architecture, and spurred considerable research activity across the natural and social sciences. Here, we introduce cross-trait assortative mating (xAM) as an alternative explanation for observed genetic correlations. We observe that xAM is common across a broad array of phenotypes and that phenotypic cross-mate correlation estimates are strongly associated with genetic correlation estimates (R2 = 76%). Then, we present theoretical and simulation-based results demonstrating that, under xAM, genetic correlation estimators yield significant estimates even for traits with entirely distinct genetic bases. We demonstrate that existing xAM plausibly accounts for substantial fractions of genetic correlation estimates in two large samples (N = 827,960). For example, previously reported genetic correlation estimates between many pairs of psychiatric disorders are fully consistent with xAM alone. Finally, we provide evidence for a history of xAM at the genetic level using a novel approach based on cross-trait even/odd chromosome polygenic score correlations. Together, our results demonstrate that previous reports have likely overestimated the true genetic similarity between many phenotypes.
Enhancing the Fitness of Embryoid Bodies and Organoids by Chemical Cytoprotection
Authors: Ryu Seungmi , Weber Claire , Chu Pei-Hsuan , Tristan Carlos A. , Ernest Ben , Jovanovic Vukasin M. , Deng Tao , Slamecka Jaroslav , Hong Hyenjong , Braisted John , Hirst Marissa , Simeonov Anton , Voss Ty C. , Singeç Ilyas
Published: March 2022

Embryoid bodies (EBs) and self-organizing organoids derived from human pluripotent stem cells (hPSCs) recapitulate tissue development in a dish and hold great promise for disease modeling and drug development. However, current protocols are hampered by cellular stress and apoptosis during cell aggregation, resulting in variability and impaired cell differentiation. Here, we demonstrate that EBs and various organoid models (e.g., brain, gut, and kidney) can be optimized by using the CEPT small molecule cocktail, a polypharmacology approach that ensures cytoprotection and cell survival. Application of CEPT (chroman 1, emricasan, polyamines, trans-ISRIB) for just 24 hours during cell aggregation has long-lasting consequences affecting morphogenesis, gene expression, and cellular differentiation. Various qualification methods confirmed that CEPT treatment consistently improved EB and organoid fitness as compared to the widely used ROCK inhibitor Y-27632. Collectively, we discovered that stress-free cell aggregation and superior cell survival in the presence of CEPT are critical quality control determinants that establish a robust foundation for bioengineering complex tissue and organ models.
BNIP3 upregulation characterizes cancer cell subpopulation with increased fitness and proliferation
Authors: Zhu Yanyan , Chen Bowang , Yan Junya , Zhao Wendi , Dou Pengli , Sun Na , Wang Yaokai , Huang Xiaoyun
Published: March 2022

BNIP3 is a BH3 only protein with both pro-apoptotic and pro-survival roles depending on the cellular context. It remains unclear how BNIP3 RNA level dictates cell fate decisions of cancer cells. Here we undertook a quantitative analysis of BNIP3 expression and functions in single cell datasets of various epithelial malignancies. Our results demonstrated that BNIP3 upregulation characterizes cancer cell subpopulations with increased fitness and proliferation. We further validated the upregulation of BNIP3 in liver cancer organoids compared with 2D culture. Taken together, the combination of in silico perturbations using public single cell datasets and experimental cancer modeling using organoids ushered in a new approach to address cancer heterogeneity.
Mooney Face Image Processing in Deep Convolutional Neural Networks Compared to Humans
Authors: Zeman Astrid , Leers Tim , de Beeck Hans Op
Published: March 2022

Deep Convolutional Neural Networks (CNNs) are criticised for their reliance on local shape features and texture rather than global shape. We test whether CNNs are able to process global shape information in the absence of local shape cues and texture by testing their performance on Mooney stimuli, which are face images thresholded to binary values. More specifically, we assess whether CNNs classify these abstract stimuli as face-like, and whether they exhibit the face inversion effect (FIE), where upright stimuli are classified positively at a higher rate compared to inverted. We tested two standard networks, one (CaffeNet) trained for general object recognition and another trained specifically for facial recognition (DeepFace). We found that both networks perform perceptual completion and exhibit the FIE, which is present over all levels of specificity. By matching the false positive rate of CNNs to humans, we found that both networks performed closer to the human average (85.73% for upright, 57.25% for inverted) for both conditions (61.31% and 62.70% for upright, 48.61% and 42.26% for inverted, for CaffeNet and DeepFace respectively). Rank order correlation between CNNs and humans across individual stimuli shows a significant correlation in upright and inverted conditions, indicating a relationship in image difficulty between observers and the model. We conclude that in spite of the texture and local shape bias of CNNs, which makes their performance distinct from humans, they are still able to process object images holistically.
Patient-Level Clinical Expertise Enhances Prostate Cancer Recurrence Predictions with Machine Learning
Authors: Vallon Jacqueline Jil , Panjwani Neil , Ling Xi , Vij Sushmita , Srinivas Sandy , Leppert John , Bayati Mohsen , Buyyounouski Mark K.
Published: March 2022

With rising access to electronic health record data, application of artificial intelligence to create clinical risk prediction models has grown. A key component in designing these models is feature generation. Methods used to generate features differ in the degree of clinical expertise they deploy (from minimal to population-level to patient-level), and subsequently the extent to which they can extract reliable signals and be automated. In this work, we develop a new process that defines how to systematically implementpatient-levelclinician feature generation (CFG), which leverages clinical expertise to define concepts relevant to the outcome variable, identify each concept’s associated features, and finally extract most features on a per-patient level by manual chart review. We subsequently apply this method to identifying and extracting patient-level features predictive of cancer recurrence from progress notes for a cohort of prostate cancer patients. We evaluate the performance of the CFG process against an automated feature generation (AFG) process via natural language processing techniques. The machine learning outcome prediction model leveraging the CFG process has a mean AUC-ROC of 0.80, in comparison to the AFG model that has a mean AUC-ROC of 0.74. This relationship remains qualitatively unchanged throughout extensive sensitivity analyses. Our analyses illustrate the value of in-depth specialist reasoning in generating features from progress notes and provide a proof of concept that there is a need for new research on efficient integration of in-depth clinical expertise into feature generation for clinical risk prediction.
Normative cognitive scores in western India, stratified by age, rurality, cognitive domains, and psychiatric comorbidity
Authors: Sundar Uma , Mukhopadhyay Amita , Sundar Suresh , Shah Nilesh
Published: March 2022

Background and objectives

Indian ethnic and educational diversities necessitate obtaining normative cognitive data in different populations. We aimed to evaluate cognitive scores using a Marathi translation of the Kolkata Cognitive Battery (KCB), and to study the association of KCB components with depression and socio-demographic variables.

Methodology

We studied 2651 individuals aged ≥40 years, without pre-existing neuropsychiatric conditions, from urban (Mumbai) and rural districts of Maharashtra. For each component of KCB, the lowest 10th percentile score was used to define cognitive impairment.

Results

We studied 1435 (54%) rural and 1216 (46%) urban residents equally divided by gender (1316 women, 1335 men), average age 54 years. KCB scores were significantly lower with female sex, older age, illiteracy and depression. The largest effect sizes attributable to these factors were in the domains of calculation (gender), visuo-constructional ability (VCA; rurality) and verbal fluency (VF; depression). Scores remained significantly lower in rural residents after controlling for age, sex and education, particularly for VCA, immediate recall and calculation.

Conclusion

This Marathi KCB having been validated on large urban as well as rural samples, may be used to study cognition in Marathi speaking populations with appropriate cut-offs tailored to the degree of urbanization of the population.
Genetically predicted on-statin LDL response is associated with higher intracerebral hemorrhage risk
Authors: Mayerhofer Ernst , Malik Rainer , Parodi Livia , Burgess Stephen , Harloff Andreas , Dichgans Martin , Rosand Jonathan , Anderson Christopher D , Georgakis Marios K
Published: March 2022

Statins lower low-density lipoprotein (LDL) cholesterol and are widely used for the prevention of atherosclerotic cardiovascular disease. Whether statin-induced LDL reduction increases risk of intracerebral hemorrhage (ICH) has been debated for almost two decades. Here, we explored whether genetically predicted on-statin LDL response is associated with ICH risk using Mendelian Randomization. Utilizing genomic data from randomized trials, we derived a polygenic score from 35 single nucleotide polymorphisms (SNP) of on-statin LDL response and tested it in the population-based UK-Biobank (UKB). We extracted statin drug and dose information from primary care data on a subset of 225,195 UKB participants covering a period of 29 years. We validated the effects of the genetic score on longitudinal LDL measurements with generalized mixed models and explored associations with incident ICH using Cox regression analysis. Statins were prescribed at least once to 75,973 (31%) of the study participants (mean 57 years, 55% females). Among statin users, mean LDL decreased by 3.45 mg/dl per year (95% CI: [-3.47, -3.42]) over follow-up. A higher genetic score of statin response (one SD increment) was associated with significant additional reductions in LDL levels (−0.05 mg/dl per year, [-0.07, -0.02]), showed concordant lipidomic effects on other lipid traits as statin use, and was associated with a lower risk for incident myocardial infarction (HR per SD increment 0.98 95% CI [0.96, 0.99]) and peripheral artery disease (HR per SD increment 0.92 95% CI [0.86, 0.98]). Over a 11-year follow-up period, a higher genetically predicted statin response among statin users was associated with higher ICH risk in a model adjusting for statin dose (HR per SD increment 1.15, 95% CI [1.04, 1.27]). On the contrary, there was no association with ICH risk among statin non-users (p=0.89). These results provide further support for the hypothesis that statin-induced LDL reduction may be causally associated with ICH risk. While the net benefit of statins for preventing vascular disease is well-established, these results provide insights about the personalized response to statin intake and the role of pharmacologic LDL-lowering in the pathogenesis of ICH.
Research on the Emotions of Uninfected People during the COVID-19 Epidemic in China
Authors: Chen Gang , Yue Juan-Juan
Published: March 2022

Background

The negative emotions induced by the ongoing coronavirus disease 2019 (COVID-19) epidemic are affecting people’s health. In order to identify emotional problems and promote early intervention to reduce the risk of disease, we studied the emotional states of Chinese people during the epidemic.

Method

We adopted the Automated Neuropsychological Assessment Metrics mood scale and prepared an online questionnaire. Then, we conducted an exploratory factor analysis of the effective responses of 567 participants from 31 provinces and cities in China. Finally, we analyzed the characteristics of the distribution of different types of emotions and compared them via several statistical methods.

Results

The original scale was modified to have six dimensions that yielded reliable internal consistency values ranging from 0.898 to 0.965 and explained 74.96% of the total variance. We found that a total of 33.9% of respondents felt negative emotions more strongly, were less happy and had less energy than other respondents (p<0.001). People with these traits had relatively serious emotional problems and were typically over 60 years old, doctoral degree holders, enterprise personnel and residents in an outbreak area.

Conclusion

Thirty-three percent of people without COVID-19 had emotional problems. Psychotherapy should be provided as early as possible for people with emotional problems caused by the epidemic, and the modified scale could be used to survey the public’s mood during public health events to detect problems and facilitate early intervention.
A comparison of paediatric hypertension clinical practice guidelines and their ability to predict adult hypertension in an African birth cohort
Authors: Craig Ashleigh , Ware Lisa J , Mapanga Witness , Norris Shane A
Published: March 2022

It remains unclear which paediatric hypertension clinical practice guideline (CPG) should be applied in an African population. We therefore aimed to compare three commonly used CPG (2017 AAP, 2016 ESH and 2004 Fourth Report) developed in high-income countries for use in South African children at four paediatric ages (children: 5yrs and 8yrs; adolescents: 13yrs and 17yrs) to determine which best predicts elevated blood pressure (EBP) in young adulthood (22yrs and 28yrs). Moreover, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each specific paediatric CPG was calculated. The 2017 AAP definition identified more children and adolescents with hypertension when compared to the 2004 Fourth Report and 2016 ESH guidelines. In computed hazards ratios, from ages 8yrs to 17yrs, all three paediatric CPG significantly predicted the risk of EBP in young adulthood (p≤0.008). However, sensitivity to predict EBP at age 22yrs for all CPG was generally low (17.0% - 33.0%) with higher specificity (87.4% - 93.1%). Sensitivity increased at age 28yrs (51.4.0% - 70.1%), while specificity decreased (52.8% - 65.1%). Both PPV and NPV at both adult age points varied widely (17.9% - 79.9% and 29.3% - 92.5% respectively). The performance of these paediatric CPG in terms of AUC were not optimal at both adult age points, however, the AAP definition at 17yrs met an acceptable level of performance (AUC= 0.71). Our results highlight the need for more research to examine if an African-specific CPG would better identify high-risk children to minimise their trajectory towards adult hypertension.
Medication Against Conflict
Authors: Berlanda Andrea , Cervellati Matteo , Esposito Elena , Rohner Dominic , Sunde Uwe
Published: March 2022

The consequences of successful public health interventions for social violence and conflict are largely unknown. This paper closes this gap by evaluating the effect of a major health intervention – the successful expansion of anti-retroviral therapy (ART) to combat the HIV/AIDS pandemic – in Africa. To identify the effect, we combine exogenous variation in the scope for treatment and global variation in drug prices. We find that the ART expansion significantly reduced the number of violent events in African countries and sub-national regions. The effect pertains to social violence and unrest, not civil war. The evidence also shows that the effect is not explained by general improvements in economic prosperity, but related to health improvements, greater approval of government policy, and increased trust in political institutions. Results of a counterfactual simulation reveal the largest potential gains in countries with intermediate HIV prevalence where disease control has been given relatively low priority.

JEL-classification: C36, D47, I15, O10
Risk of death following SARS-CoV-2 infection or COVID-19 vaccination in young people in England: a self-controlled case series study
Authors: Nafilyan Vahé , Bermingham Charlotte , Ward Isobel L. , Morgan Jasper , Zaccardi Francesco , Khunti Kamlesh , Stanborough Julie , Banerjee Amitava
Published: March 2022

Objectives

To assess whether there is a change in the incidence of cardiac and all-cause death in young people following COVID-19 vaccination or SARS-CoV-2 infection in unvaccinated individuals.

Design

Self-controlled case series.

Setting

National, linked electronic health record data in England.

Study population

Individuals aged 12-29 who had received at least one dose of COVID-19 vaccination and died between 8 December 2020 and 2 February 2022 and registered by 16 February 2022 within 12 weeks of COVID-19 vaccination; Individuals aged 12-29 who died within 12 weeks of testing positive for SARS-CoV-2.

Main outcome measures

Cardiac and all-cause deaths occurring within 12 weeks of vaccination or SARS-CoV-2 infection.

Results

Compared to the baseline period, there was no evidence of a change in the incidence of cardiac death in the six weeks after vaccination, whether for each of weeks 1 to 6 or the whole six-week period. There was a decrease in the risk of all-cause death in the first week after vaccination and no change in each of weeks 2 to 6 after vaccination or whole six-week period after vaccination. Subgroup analyses by sex, age, vaccine type, and last dose also showed no change in the risk of death in the first six weeks after vaccination. There was a large increase in the incidence of cardiac and all-cause death in the overall risk period after SARS-CoV-2 infection among the unvaccinated.

Conclusion

There is no evidence of an association between COVID-19 vaccination and an increased risk of death in young people. By contrast, SARS-CoV-2 infection was associated with substantially higher risk of cardiac related death and all-cause death.

What is already known on this topic

Several studies have highlighted the association between COVID-19 vaccination and the risk of myocarditis, myopericarditis, and other cardiac problems, especially in young people, but associated risk of mortality is unclear. Since younger people have lower risk of COVID-19 hospitalisation and mortality, the mortality risk associated with vaccination is potentially more important to them in balancing the risk and benefit of vaccination.

What this study adds

Although there is a risk of myocarditis or myopericarditis with COVID-19, there is no evidence of increased risk of cardiac or all-cause mortality following COVID-19 vaccination in young people aged 12 to 29. Given the increased risk of mortality following SARS-CoV-2 infection in this group, the risk-benefit analysis favours COVID-19 vaccination for this age group.
Systematic Review and Meta-analysis of Mental Health Impact on BAME Populations with Preterm Birth
Authors: Delanerolle G , Zeng Y , Phiri P , Phan T , Tempest N , Busuulwa P , Shetty A , Raymont V , Rathod S , Shi JQ , Hapangama DK
Published: March 2022

Background

Preterm birth (PTB) is one of the main causes of neonatal deaths globally, with approximately 15 million infants are born preterm. Therefore, the mental health (MH) impact experienced by mothers experiencing a PTB is important, especially within the Black, Asian and Minority Ethnic (BAME) populations.

Aim

The aims of the study were to determine the prevalence of MH conditions among BAME women with PTB as well as the MH assessments used to characterise the MH outcomes.

Methods

A systematic methodology was developed and published as a protocol in PROSPERO (CRD42020210863). Multiple databases were used to extract relevant data. I2 and Egger’s tests were used to detect the heterogeneity and publication bias. A Trim and fill method was used to demonstrate the influence of publication bias and the credibility of conclusions.

Results

Thirty-nine studies met the eligibility criteria from a possible 3526. The prevalence rates of depression among PTB-BAME mothers were significantly higher than full-term mothers with a standard median deviation (SMD) of 1.5 and a 95% confidence interval (CI) 29-74%. The subgroup analysis indicated, depressive symptoms to be time sensitive. Women within the very PTB category demonstrated a significantly higher prevalence of depression than those categorised as non-very PTB. The prevalence rates of anxiety and stress among PTB-BAME mothers were significantly higher than full-term mothers (OR of 88% and 60% with a CI of 42%-149% and 24-106%, respectively).

Conclusion

BAME women with PTB suffers with MH conditions. Many studies did not report on BAME population specific MH outcomes. Therefore, the impact of PTB is not accurately represented in this population, and thus could negatively influence the quality of maternity services.

Core Tip

This study demonstrates the mental health impact due to preterm birth among the Black, Asian and Ethnic minority women. There is minimal research available at present around this subject matter, and potential disease sequalae.
The World Health Organization’s Disease Outbreak News: a retrospective database
Authors: Carlson Colin J. , Boyce Matthew R. , Dunne Margaret , Graeden Ellie , Lin Jessica , Abdellatif Yasser Omar , Palys Max A. , Pavez Munir , Phelan Alexandra L. , Katz Rebecca
Published: March 2022

The World Health Organization (WHO) notifies the global community about disease outbreaks through the Disease Outbreak News (DON). These online reports tell important stories about both outbreaks themselves and the high-level decision making that governs information sharing during public health emergencies. However, they have been used only minimally in global health scholarship to date. Here, we collate all 2,789 of these reports from their first use through the start of the Covid-19 pandemic (January 1996 to December 2019), and develop an annotated database of the subjective and often inconsistent information they contain. We find that these reports are dominated by a mix of persistent worldwide threats (particularly influenza and cholera) and persistent epidemics (like Ebola virus disease in Africa or MERS-CoV in the Middle East), but also document important periods in history like the anthrax bioterrorist attacks at the turn of the century, the spread of chikungunya and Zika virus to the Americas, or even recent lapses in progress towards polio elimination. We present three simple vignettes that show how researchers can use these data to answer both qualitative and quantitative questions about global outbreak dynamics and public health response. However, we also find that the retrospective value of these reports is visibly limited by inconsistent reporting (e.g., of disease names, case totals, mortality, and actions taken to curtail spread). We conclude that sharing a transparent rubric for which outbreaks are considered reportable, and adopting more standardized formats for sharing epidemiological metadata, might help make the DON more useful to researchers and policymakers.
TheVenturia inaequaliseffector repertoire is expressed in waves and is dominated by expanded families with predicted structural similarity to avirulence proteins from other plant-pathogenic fungi
Authors: Rocafort Mercedes , Bowen Joanna K. , Hassing Berit , Cox Murray P. , McGreal Brogan , de la Rosa Silvia , Plummer Kim M. , Bradshaw Rosie E. , Mesarich Carl H.
Published: March 2022

Background

Scab, caused by the biotrophic fungusVenturia inaequalis, is the most economically important disease of apples worldwide. During infection,V. inaequalisoccupies the subcuticular environment, where it secretes virulence factors, termed effectors, to promote host colonization. Consistent with other plant-pathogenic fungi, many of these effectors are expected to be non-enzymatic proteins, some of which can be recognized by corresponding host resistance proteins to activate plant defences, thus acting as avirulence determinants. To develop durable control strategies against scab, a better understanding of the roles that these effector proteins play in promoting subcuticular growth byV. inaequalis, as well as in activating, suppressing or circumventing resistance protein-mediated defences in apple, is required.

Results

We generated the first comprehensive RNA-seq transcriptome ofV. inaequalisduring colonization of apple. Analysis of this transcriptome revealed five temporal waves of gene expression that peaked during early, mid or mid-late infection. While the number of genes encoding secreted, non-enzymatic proteinaceous effector candidates (ECs) varied in each wave, most belonged to waves that peaked in expression during mid-late infection. Spectral clustering based on sequence similarity determined that the majority of ECs belonged to expanded protein families. To gain insights into function, the tertiary structures of ECs were predicted using AlphaFold2. Strikingly, despite an absence of sequence similarity, many ECs were predicted to have structural similarity to avirulence proteins from other plant-pathogenic fungi, including members of the MAX, LARS, ToxA and FOLD effector families. In addition, several other ECs, including an EC family with sequence similarity to the AvrLm6 avirulence effector fromLeptosphaeria maculans, were predicted to adopt a KP6-like fold. Thus, proteins with a KP6-like fold represent another structural family of effectors shared among plant-pathogenic fungi.

Conclusions

Our study reveals the transcriptomic profile underpinning subcuticular growth byV. inaequalisand provides an enriched list of ECs that can be investigated for roles in virulence and avirulence. Furthermore, our study supports the idea that numerous sequence-unrelated effectors across plant-pathogenic fungi share common structural folds. In doing so, our study gives weight to the hypothesis that many fungal effectors evolved from ancestral genes through duplication, followed by sequence diversification, to produce sequence-unrelated but structurally similar proteins.
Classifying the activity states of small vertebrates using automated VHF telemetry
Authors: Gottwald Jannis , Royauté Raphaël , Becker Marcel , Geitz Tobias , Höchst Jonas , Lampe Patrick , Leister Lea , Lindner Kim , Maier Julia , Rösner Sascha , Schabo Dana G. , Freisleben Bernd , Brandl Roland , Müller Thomas , Farwig Nina , Nauss Thomas
Published: March 2022

The most basic behavioural states of animals can be described as active or passive. However, while high-resolution observations of activity patterns can provide insights into the ecology of animal species, few methods are able to measure the activity of individuals of small taxa in their natural environment. We present a novel approach in which the automated VHF radio-tracking of small vertebrates fitted with lightweight transmitters (< 0.2 g) is used to distinguish between active and passive behavioural states.

A dataset containing > 3 million VHF signals was used to train and test a random forest model in the assignment of either active or passive behaviour to individuals from two forest-dwelling bat species (Myotis bechsteinii(n = 50) andNyctalus leisleri(n = 20)). The applicability of the model to other taxonomic groups was demonstrated by recording and classifying the behaviour of a tagged bird and by simulating the effect of different types of vertebrate activity with the help of humans carrying transmitters. The random forest model successfully classified the activity states of bats as well as those of birds and humans, although the latter were not included in model training (F-score 0.96–0.98).

The utility of the model in tackling ecologically relevant questions was demonstrated in a study of the differences in the daily activity patterns of the two bat species. The analysis showed a pronounced bimodal activity distribution ofN. leisleriover the course of the night while the night-time activity ofM. bechsteiniiwas relatively constant. These results show that significant differences in the timing of species activity according to ecological preferences or seasonality can be distinguished using our method.

Our approach enables the assignment of VHF signal patterns to fundamental behavioural states with high precision and is applicable to different terrestrial and flying vertebrates. To encourage the broader use of our radio-tracking method, we provide the trained random forest models together with an R-package that includes all necessary data-processing functionalities. In combination with state-of-the-art open-source automated radio-tracking, this toolset can be used by the scientific community to investigate the activity patterns of small vertebrates with high temporal resolution, even in dense vegetation.