bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional multilayer concentric bipolar electrodes restrict spatial activation in optic nerve stimulation
Authors: Borda Eleonora , Gaillet Vivien , Airaghi Leccardi Marta Jole Ildelfonsa , Zollinger Elodie Geneviève , Moreira Ricardo Camilo , Ghezzi Diego
Published: May 2022

Objective. Intraneural nerve interfaces often operate in a monopolar configuration with a common and distant ground electrode. This configuration leads to a wide spreading of the electric field. Therefore, this approach is suboptimal for intraneural nerve interfaces when selective stimulation is required. Approach. We designed a multilayer electrode array embedding three-dimensional concentric bipolar (CB) electrodes. First, we validated the higher stimulation selectivity of this new electrode array compared to classical monopolar stimulation using simulations. Next, we compared them in-vivo by intraneural stimulation of the rabbit optic nerve and recording evoked potentials in the primary visual cortex. Main results. Simulations showed that three-dimensional CB electrodes provide a high localisation of the electric field in the tissue so that electrodes are electrically independent even for high electrode density. Experiments in-vivo highlighted that this configuration restricts spatial activation in the visual cortex due to the fewer fibres activated by the electric stimulus in the nerve. Significance. Highly focused electric stimulation is crucial to achieving high selectivity in fibre activation. The multilayer array embedding three-dimensional CB electrodes improves selectivity in optic nerve stimulation. This approach is suitable for other neural applications, including bioelectronic medicine.
Developing a physics understanding of the quasi-continuous exhaust regime: pedestal profile and ballooning stability analysis
Authors: Radovanovic L. , Dunne M. , Wolfrum E. , Harrer G. , Faitsch M. , Fischer R. , Aumayr F.
Published: May 2022

It has been experimentally observed that at ASDEX Upgrade (AUG) plasmas at relatively high shaping, an increase of gas fuelling corresponds to an increase of the frequency and intensity of the type-I edge localised modes (ELMs). At high enough fuelling, the plasma enters the quasi continuous exhaust (QCE) regime. We have performed ideal ballooning n → ∞ stability analysis on four AUG discharges, comparing the type-I ELM dominated phases, with the phases that are in the QCE regime. The results of this study show that as the gas puff increases, the plasma gets more ballooning unstable in the pedestal region, especially very close to the separatrix, at the pedestal bottom. On the contrary, in the middle of the pedestal, the discharges are more ballooning stable. Here the locally negative magnetic shear has a stabilising effect on ballooning modes, allowing access to the second stability region. Our analysis of the ballooning stability and the confinement factor H98 suggest that with optimisation of the pedestal shape, good confinement without type-I ELMs can be achieved. Necessary ingredients are that the region of the highest pressure gradient is not ideal ballooning limited, while the pedestal bottom is ballooning unstable. Ideal stability analysis of 36 simulated ITER profiles shows that, similarly to the experimental cases from AUG, a high pedestal top pressure can be maintained concomitant with a ballooning instability at the pedestal bottom, making QCE a promising scenario.
Current correlations, Drude weights and large deviations in a box–ball system
Authors: Kuniba Atsuo , Misguich Grégoire , Pasquier Vincent
Published: May 2022

We explore several aspects of the current fluctuations and correlations in the box–ball system, an integrable cellular automaton in one space dimension. The state we consider is an ensemble of microscopic configurations where the box occupancies are independent random variables (i.i.d. state), with a given mean ball density. We compute several quantities exactly in such homogeneous stationary state: the mean value and the variance of the number of balls N

t
crossing the origin during time t, and the scaled cumulants generating function associated to N

t
. We also compute two spatially integrated current–current correlations. The first one, involving the long-time limit of the current–current correlations, is the so-called Drude weight and is obtained with thermodynamic Bethe ansatz (TBA). The second one, involving equal time current–current correlations is calculated using a transfer matrix approach. A family of generalized currents, associated to the conserved charges and to the different time evolutions of the models are constructed. The long-time limits of their correlations generalize the Drude weight and the second cumulant of N

t
and are found to obey nontrivial symmetry relations. They are computed using TBA and the results are found to be in good agreement with microscopic simulations of the model. TBA is also used to compute explicitly the whole family of flux Jacobian matrices. Finally, some of these results are extended to a (non-i.i.d.) two-temperatures generalized Gibbs state (with one parameter coupled to the total number of balls, and another one coupled to the total number of solitons).
Index of a singular point of a vector field or of a 1-form on an orbifold
Authors: Gusein-Zade S.
Published: May 2022

Indices of singular points of a vector field or of a 1-form on a smooth manifold are closely related to the Euler characteristic through the classical Poincaré–Hopf theorem. Generalized Euler characteristics (additive topological invariants of spaces with some additional structures) are sometimes related to corresponding analogs of indices of singular points. Earlier, a notion of the universal Euler characteristic of an orbifold was defined. It takes values in a ring

R

\mathcal {R}

, as an Abelian group freely generated by the generators, corresponding to the isomorphism classes of finite groups. Here the universal index of an isolated singular point of a vector field or of a 1-form on an orbifold is defined as an element of the ring

R

\mathcal {R}

. For this index, an analog of the Poincaré–Hopf theorem holds.
Dihedral modules with ∞-simplicial faces and dihedral homology for involutive 𝐴_{∞}-algebras over rings
Authors: Lapin S.
Published: May 2022

On the basis of combinatorial techniques of dihedral modules with

∞
\infty

-simplicial faces, dihedral homology is constructed for involutive

A

∞

A_{\infty }

-algebras over arbitrary commutative unital rings.
Apolipoprotein E*Ɛ2 carriers exhibit high aspirin-treated platelet reactivity and low cardiovascular risk during long-term aspirin treatment
Authors: Li Xiao-Li , Wang Qiang , Jia Guo-Dong , Yin Hui-Jun , Wang Yao-Hui , Hu Chao , Wang Xiao-Qing , Yang Yang
Published: May 2022

Objective

Apolipoprotein E (APOE) loci, including rs429358 (Ɛ4) and rs7412 (Ɛ2), are involved in cardiovascular (CV) health. However, their effect on the CV-protective effect of aspirin remains unknown.

Methods

A total of 515 aspirin-treated individuals with existing CV diseases were recruited, and their APOE genotypes, platelet functions and other routine laboratory parameters were assessed when they enrolled. The first major CV events (myocardial infarction, stroke, revascularisation and CV death) and all CV events (major CV events plus unstable angina and transient ischaemic attack) during a mean 5.2-year follow-up period were recorded.

Results

After adjusting for age, gender, BMI, lifestyle, lipid profiles and other CV drugs and comorbidities, Ɛ2 carriers were found to exhibit ~80% lower risk of major CV and 60% lower risk of all CV (HR = 0.186, CI: 0.048–0.715, P = 0.014; HR = 0.435, CI: 0.234–0.812, P = 0.009, respectively) than Ɛ2 noncarriers. Furthermore, high incidence of high platelet reactivity assessed by arachidonic acid-induced light transmission aggregometry (23.4 vs. 13.7%, P = 0.038), triglyceride and haemoglobin and low low-density lipoprotein were observed. Ɛ4 carriers had slightly increased cholesterol and hypercholesterolemia incidence relative to Ɛ4 noncarriers.

Conclusions

Our results demonstrated that APOE*Ɛ2 carriers can derive additional CV benefit from long-term aspirin treatment. Moreover, it was observed that APOE2 interacts with cyclooxygenase-1 (COX-1) and upregulates its activity. The CV-protective effect of aspirin in Ɛ2 carriers is likely attributed to APOE2 upregulating vascular COX-1-mediated CV protective pathway, together with aspirin partially inhibiting platelet COX-1-mediated platelet aggregation.
Negligible Specimen Hemolysis Is Observed With Sarstedt S-Monovette Coagulation Tubes in Aspiration Mode
Authors: Çat Abdulkadir , Uçar Kamil Taha
Published: May 2022

Objectives

We aimed to compare the levels of hemolysis in the blood collected using the vacuum and aspiration modes via Sarstedt S-Monovette coagulation tubes.

Methods

Forty volunteers were included in the study. Blood samples were collected using two different modes in the S-Monovette citrate tube (Sarstedt AG). Prothrombin time, active partial thromboplastin time, fibrinogen, and D-dimer analyses were performed using the STA-Compact-Max 3 analyzer (Stago). The hemolysis levels of the samples were measured by both Stago’s semiquantitative hemolysis index (H-index) module and the quantitative H-index measurement of the Roche cobas 6000 (Roche Diagnostics) analyzer.

Results

Roche’s quantitative H-index values were statistically significantly lower in the aspiration mode. No clinically significant difference was observed between coagulation test results.

Conclusions

Using the S-Monovette citrate tubes can reduce spurious hemolysis and improve patient safety.
An overlooked dispersal route of Cardueae (Asteraceae) from the Mediterranean to East Asia revealed by phylogenomic and biogeographical analyses ofAtractylodes
Authors: Xia Maoqin , Cai Minqi , Comes Hans Peter , Zheng Li , Ohi-Toma Tetsuo , Lee Joongku , Qi Zhechen , Konowalik Kamil , Li Pan , Cameron Kenneth M , Fu Chengxin
Published: May 2022

Background and Aims

The East Asian–Tethyan disjunction pattern and its mechanisms of formation have long been of interest to researchers. Here, we studied the biogeographical history of Asteraceae tribe Cardueae, with a particular focus on the temperate East Asian genus Atractylodes DC., to understand the role of tectonic and climatic events in driving the diversification and disjunctions of the genus.

Methods

A total of 76 samples of Atractylodes from 36 locations were collected for RAD-sequencing. Three single nucleotide polymorphism (SNP) datasets based on different filtering strategies were used for phylogenetic analyses. Molecular dating and ancestral distribution reconstruction were performed using both chloroplast DNA sequences (127 Cardueae samples) and SNP (36 Atractylodes samples) datasets.

Key Results

Six species of Atractylodes were well resolved as individually monophyletic, although some introgression was identified among accessions of A. chinensis, A. lancea and A. koreana. Dispersal of the subtribe Carlininae from the Mediterranean to East Asia occurred after divergence between Atractylodes and Carlina L. + Atractylis L. + Thevenotia DC. at ~31.57 Ma, resulting in an East Asian–Tethyan disjunction. Diversification of Atractylodes in East Asia mainly occurred from the Late Miocene to the Early Pleistocene.

Conclusions

Aridification of Asia and the closure of the Turgai Strait in the Late Oligocene promoted the dispersal of Cardueae from the Mediterranean to East China. Subsequent uplift of the Qinghai–Tibet Plateau as well as changes in Asian monsoon systems resulted in an East Asian–Tethyan disjunction between Atractylodes and Carlina + Atractylis + Thevenotia. In addition, Late Miocene to Quaternary climates and sea level fluctuations played major roles in the diversification of Atractylodes. Through this study of different taxonomic levels using genomic data, we have revealed an overlooked dispersal route between the Mediterranean and far East Asia (Japan/Korea) via Central Asia and East China.
Striking the Balance? On the Relationship Between Public and Private Security in Western Countries
Authors: Wenzelburger Georg , Staff Helge
Published: May 2022

Much writing in comparative criminology on the punitive turn and developments in Western penal states has focused on how the state provides security to its citizens. However, the number of private guards exceeds those of police officers in many European countries, and private security services carry out numerous law and order tasks. Our paper links the literature on private security with comparative penal policy studies. It explores how the cross-national variance in the relative importance of public and private security—which we term ‘the security balance’ – can be explained by quantitatively analysing data on public and private security in 23 European countries from 2009 to 2018. We contribute to the literature on crime and politics by highlighting the significant role of private security in today’s balance of security provision.
Conceptualizing cross-sectoral partnership building in two small central Appalachian towns
Authors: Moayerian Neda , Nagle Lara , Stephenson Max
Published: May 2022

This article highlights the efforts of two rural communities located in Central Appalachia to address the conflicts and economic and social challenges that have arisen in each as a result of the decline of coal mining. Documenting and analyzing the processes and narratives gleaned from the authors’ long-term interaction with stakeholders in the two communities through field tours, community meetings, individual conversations, and group workshops revealed specific social and economic forces, including neoliberal ideology and the realities of its assumptions and public policies, as key forces shaping current community challenges. This article assesses the effectiveness of cross-sectoral partnerships constructed in both case communities aimed at addressing resource dependence, social legitimation, exchange needs, and strategic collaboration imperatives. We used Meadows’ systems thinking construct to identify the system elements that informed this analysis and to assess the efficacy of cross-sector partnership building in questioning dominant imaginaries and creating novel ways of being within communities undergoing transition from what have otherwise been economically and socially oppressive conditions. We found that stakeholders within the two communities have often struggled to maintain the cross-sectoral partnerships they have sought to create, let alone understand fully the outcomes of any intervention they might launch, despite their best intentions and plans. A lack of continuing communication among relevant stakeholders, limitations to encouraging citizens’ agential activities, and adopting strategies within the assumptions of the dominant neoliberal paradigm were among the main hindrances to realizing effective partnerships in the communities we analyzed.
Saccades and presaccadic stimulus repetition alter cortical network topology and dynamics: evidence from EEG and graph theoretical analysis
Authors: Ghaderi Amirhossein , Niemeier Matthias , Crawford John Douglas
Published: May 2022

Parietal and frontal cortex are involved in saccade generation, and their output signals modify visual signals throughout cortex. Local signals associated with these interactions are well described, but their large-scale progression and network dynamics are unknown. Here, we combined source localized electroencephalography (EEG) and graph theory analysis (GTA) to understand how saccades and presaccadic visual stimuli interactively alter cortical network dynamics in humans. Twenty-one participants viewed 1–3 vertical/horizontal grids, followed by grid with the opposite orientation just before a horizontal saccade or continued fixation. EEG signals from the presaccadic interval (or equivalent fixation period) were used for analysis. Source localization-through-time revealed a rapid frontoparietal progression of presaccadic motor signals and stimulus-motor interactions, with additional band-specific modulations in several frontoparietal regions. GTA analysis revealed a saccade-specific functional network with major hubs in inferior parietal cortex (alpha) and the frontal eye fields (beta), and major saccade-repetition interactions in left prefrontal (theta) and supramarginal gyrus (gamma). This network showed enhanced segregation, integration, synchronization, and complexity (compared with fixation), whereas stimulus repetition interactions reduced synchronization and complexity. These cortical results demonstrate a widespread influence of saccades on both regional and network dynamics, likely responsible for both the motor and perceptual aspects of saccades.
Competing Responses to Global Inequalities in Access to COVID Vaccines: Vaccine Diplomacy and Vaccine Charity Versus Vaccine Liberty
Authors: Sparke Matthew , Levy Orly
Published: May 2022

Global access to coronavirus vaccines has been extraordinarily unequal and remains an ongoing source of global health insecurities from the evolution of viral variants in the bodies of the unvaccinated. There have nevertheless been at least 3 significant alternatives developed to this disastrous bioethical failure. These alternatives are reviewed in this article in the terms of “vaccine diplomacy,” “vaccine charity,” and “vaccine liberty.” Vaccine diplomacy includes the diverse bilateral deliveries of vaccines organized by the geopolitical considerations of countries strategically seeking various kinds of global and regional advantages in international relations. Vaccine charity centrally involves the humanitarian work of the global health agencies and donor governments that have organized the COVAX program as an antidote to unequal access. Despite their many promises, however, both vaccine diplomacy and vaccine charity have failed to deliver the doses needed to overcome the global vaccination gap. Instead, they have unfortunately served to immunize the global vaccine supply system from more radical demands for a “people’s vaccine,” technological transfer, and compulsory licensing of vaccine intellectual property (IP). These more radical demands represent the third alternative to vaccine access inequalities. As a mix of nongovernmental organization-led and politician-led social justice demands, they are diverse and multifaceted, but together they have been articulated as calls for vaccine liberty. After first describing the realities of vaccine access inequalities, this article compares and contrasts the effectiveness thus far of the 3 alternatives. In doing so, it also provides a critical bioethical framework for reflecting on how the alternatives have come to compete with one another in the context of the vaccine property norms and market structures entrenched in global IP law. The uneven and limited successes of vaccine diplomacy and vaccine charity in delivering vaccines in underserved countries can be reconsidered in this way as compromised successes that not only compete with one another, but that have also worked together to undermine the promise of universal access through vaccine liberty.
Translational drug–interaction corpus
Authors: Zhang Shijun , Wu Hengyi , Wang Lei , Zhang Gongbo , Rocha Luis M , Shatkay Hagit , Li Lang
Published: May 2022

The discovery of drug–drug interactions (DDIs) that have a translational impact among in vitro pharmacokinetics (PK), in vivo PK and clinical outcomes depends largely on the quality of the annotated corpus available for text mining. We have developed a new DDI corpus based on an annotation scheme that builds upon and extends previous ones, where an abstract is fragmented and each fragment is then annotated along eight dimensions, namely, focus, polarity, certainty, evidence, directionality, study type, interaction type and mechanism. The guideline for defining these dimensions has undergone refinement during the annotation process. Our DDI corpus comprises 900 positive DDI abstracts and 750 that are not directly relevant to DDI. The abstracts in corpus are separated into eight categories of DDI or non-DDI evidence: DDI with pharmacokinetic (PK) mechanism, in vivo DDI PK, DDI clinical, drug–nutrition interaction, single drug, not drug related, in vitro pharmacodynamic (PD) and case report. Seven annotators, three annotators with drug–interaction research experience and four annotators with less drug–interaction research experience independently annotated the DDI corpus, where two researchers independently annotated each abstract. After two rounds of annotations with additional training in between, agreement improved from (0.79, 0.96, 0.86, 0.70, 0.91, 0.65, 0.78, 0.90) to (0.93, 0.99, 0.96, 0.94, 0.95, 0.93, 0.96, 0.97) for focus, certainty, evidence, study type, interaction type, mechanisms, polarity and direction, respectively. The novice-level annotators improved from 0.83 to 0.96, while the expert-level annotators stayed in high performance with some improvement, from 0.90 to 0.96. In summary, we achieved 96% agreement among each pair of annotators with regard to the eight dimensions. The annotated corpus is now available to the community for inclusion in their text-mining pipelines.

Database URL https://github.com/zha204/DDI-Corpus-Database/tree/master/DDI%20corpus
The impact of left atrial mechanics on adverse events and clinical outcome after cardiac surgery
Authors: Dalos Daniel , Haaser Sophie Selina , Hofer Felix , Kazem Niema , Koller Lorenz , Hammer Andreas , Steinlechner Barbara , Laufer Günther , Hengstenberg Christian , Niessner Alexander , Sulzgruber Patrick
Published: May 2022

OBJECTIVES

Postoperative atrial fibrillation (POAF) represents a common complication after cardiac surgery that is associated with unfavourable clinical outcome. Identifying patients at risk for POAF is crucial but challenging. This study aimed to investigate the prognostic potential of speckle-tracking echocardiography on POAF and fatal adverse events from a long-term perspective.

METHODS

A total of 124 patients undergoing elective cardiac surgery were prospectively enrolled and underwent preoperative speckle-tracking echocardiography. Patients were followed prospectively for the occurrence of POAF within the entire hospitalization and reaching the secondary end points cardiovascular and all-cause mortality.

RESULTS

Within the study population 43.5% (n = 53) of enrolled individuals developed POAF. After a median follow-up of 3.9 years, 25 (20.2%) patients died. We observed that patients presenting with POAF had lower global peak atrial longitudinal strain (PALS) values compared to the non-POAF arm {POAF: 14.8% [95% confidence interval (CI): 10.9–17.8] vs non-POAF: 19.4% [95% CI: 14.8–23.5], P < 0.001}. Moreover, global PALS was a strong and independent predictor for POAF [adjusted odds ratio per 1 standard deviation: 0.37 (95% CI: 0.22–0.65), P < 0.001] and independently associated with mortality [adjusted hazard ratio per 1 standard deviation: 0.63 (95% CI: 0.40–0.99), P = 0.048]. Classification and Regression Tree analysis revealed a cut-off value of <17% global PALS as high risk for both POAF and mortality.

CONCLUSIONS

Global PALS is associated with the development of POAF following surgery in an unselected patient population undergoing CABG and/or valve surgery. Since patients with global PALS <17% face a poor long-term prognosis, routine assessment of global PALS needs to be considered in terms of proper secondary prevention in the era of personalized medicine.
Variations in hazard during earthquake sequences between 1995 and 2018 in western Greece as evaluated by a Bayesian ETAS model
Authors: Azarbakht Alireza , Ebrahimian Hossein , Jalayer Fatemeh , Douglas John
Published: May 2022

Forecasting the spatio-temporal occurrence of events is at the core of Operational Earthquake Forecasting, which is of great interest for risk management, particularly during ongoing seismic sequences. Epidemic type aftershock sequence (ETAS) models are powerful tools to estimate the occurrence of events during earthquake sequences. In this context, a robust seismicity forecasting framework based on Bayesian-inference has been adapted to the Patras and Aegio region in western Greece (one of the most seismically active parts of Mediterranean), and an incremental adaptive algorithm is introduced to train the priors for ETAS model parameters. The seismicity forecasting is capable of accounting for uncertainty in the model parameters as well as variations in the sequence of events that may happen during the forecasting interval. Six seismic sequences between 1995 and 2018 were selected with main shock moment magnitudes Mw ≥ 6.0. The ETAS model was adapted for each seismic sequence. The number of forecasted events with Mw ≥ 4.5 and their spatial distribution was retrospectively compared with the as-recorded earthquake catalogue, confirming a good agreement between the forecasts and observations. The results show that the adapted model can be used immediately after a severe main shock to statistically predict potentially damaging earthquakes during the ongoing seismic sequence. The seismicity forecasts were translated to short-term daily exceedance rates for different thresholds of peak ground acceleration. The results reveal that the seismic hazard increased by up to 33 times in the case of the damaging 1995 Mw 6.5 earthquake in the city of Aegio. However, the results confirmed that in all six studied sequences, the increased seismic hazard decayed rapidly during the 2 d after the main shock, and remained relatively high in the following days (roughly ten times the long-term time-independent hazard).
Case fatality risk of diarrhoeal pathogens: a systematic review and meta-analysis
Authors: Asare Ernest O , Hergott Dianna , Seiler Jessica , Morgan Brooks , Archer Helena , Wiyeh Alison B , Guo Boya , Driver Matt , Giersing Birgitte , Hasso-Agopsowicz Mateusz , Lingappa Jairam , Lopman Benjamin A , Pitzer Virginia E
Published: May 2022

Background

Estimates of the relative contribution of different pathogens to all-cause diarrhoea mortality are needed to inform global diarrhoea burden models and prioritize interventions. We aimed to investigate and estimate heterogeneity in the case fatality risk (CFR) of different diarrhoeal pathogens.

Methods

We conducted a systematic review and meta-analysis of studies that reported cases and deaths for 15 enteric pathogens published between 1990 and 2019. The primary outcome was the pathogen-specific CFR stratified by age group, country-specific under-5 mortality rate, setting, study year and rotavirus vaccine introduction status. We developed fixed-effects and multilevel mixed-effects logistic regression models to estimate the pooled CFR overall and for each pathogen, controlling for potential predictors of heterogeneity.

Results

A total of 416 studies met review criteria and were included in the analysis. The overall crude CFR for all pathogens was 0.65%, but there was considerable heterogeneity between and within studies. The overall CFR estimated from a random-effects model was 0.04% (95% CI: 0.026%–0.062%), whereas the pathogen-specific CFR estimates ranged from 0% to 2.7%. When pathogens were included as predictors of the CFR in the overall model, the highest and lowest odds ratios were found for enteropathogenic Escherichia coli (EPEC) [odds ratio (OR) = 3.0, 95% CI: 1.28–7.07] and rotavirus (OR = 0.23, 95% CI: 0.13–0.39), respectively.

Conclusion

We provide comprehensive estimates of the CFR across different diarrhoeal pathogens and highlight pathogens for which more studies are needed. The results motivate the need for diarrhoeal interventions and could help prioritize pathogens for vaccine development.
Asymptomatic School-Aged Children Are Important Drivers of Malaria Transmission in a High Endemicity Setting in Uganda
Authors: Rek John , Blanken Sara Lynn , Okoth Joseph , Ayo Daniel , Onyige Ismail , Musasizi Eric , Ramjith Jordache , Andolina Chiara , Lanke Kjerstin , Arinaitwe Emmanuel , Olwoch Peter , Collins Katharine A , Kamya Moses R , Dorsey Grant , Drakeley Chris , Staedke Sarah G , Bousema Teun , Conrad Melissa D
Published: May 2022

Achieving malaria elimination requires a better understanding of the transmissibility of human infections in different transmission settings. This study aimed to characterize the human infectious reservoir in a high endemicity setting in eastern Uganda, using gametocyte quantification and mosquito feeding assays. In asymptomatic infections, gametocyte densities were positively associated with the proportion of infected mosquitoes (β = 1.60; 95% CI, 1.32–1.92; P < .0001). Combining transmissibility and abundance in the population, symptomatic and asymptomatic infections were estimated to contribute to 5.3% and 94.7% of the infectious reservoir, respectively. School-aged children (5–15 years old) contributed to 50.4% of transmission events and were important drivers of malaria transmission.
Head-to-Head Comparison of Bi- and Nonavalent Human Papillomavirus Vaccine-Induced Antibody Responses
Authors: Arroyo Mühr Laila Sara , Eklund Carina , Lagheden Camilla , Eriksson Tiina , Pimenoff Ville N , Gray Penelope , Lehtinen Matti , Dillner Joakim
Published: May 2022

For head-to-head comparison of human papillomavirus (HPV) antibody levels induced by different vaccines, 25-year-old vaccine-naive women were given either the bivalent (n = 188) or the nonavalent HPV vaccine (n = 184). Six months after vaccination antibodies against pseudovirions from 17 different HPV types (HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68/73) were measured. Antibodies against HPV16/18 were higher after bivalent HPV vaccination (mean international units [IU] 1140.1 and 170.5 for HPV16 and 18, respectively) than after nonavalent vaccination (265.1 and 22.3 IUs, respectively). The bivalent vaccine commonly induced antibodies against the nonvaccine HPV types 31/33/35/45 or 58. The nonavalent vaccine induced higher antibodies against HPV6/11/31/33/45/52/58 and 35.
Molecular mechanisms of acquired antifungal drug resistance in principal fungal pathogens and EUCAST guidance for their laboratory detection and clinical implications
Authors: Rogers Thomas R , Verweij Paul E , Castanheira Mariana , Dannaoui Eric , White P Lewis , Arendrup Maiken Cavling ,   Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST), Arendrup M C , Arikan-Akdagli S , Barchiesi F , Buil Jochem , Castanheira M , Chryssanthou E , Friberg N , Guinea J , Hamal P , Hilmarsdottir Ingibjorg , Klimko N , Kurzai O , Lagrou K , Lass-Flörl C , Matos T , Meletiadis J , Moore C , Muehlethaler K , Rogers T R
Published: May 2022

The increasing incidence and changing epidemiology of invasive fungal infections continue to present many challenges to their effective management. The repertoire of antifungal drugs available for treatment is still limited although there are new antifungals on the horizon. Successful treatment of invasive mycoses is dependent on a mix of pathogen-, host- and antifungal drug-related factors. Laboratories need to be adept at detection of fungal pathogens in clinical samples in order to effectively guide treatment by identifying isolates with acquired drug resistance. While there are international guidelines on how to conduct in vitro antifungal susceptibility testing, these are not performed as widely as for bacterial pathogens. Furthermore, fungi generally are recovered in cultures more slowly than bacteria, and often cannot be cultured in the laboratory. Therefore, non-culture-based methods, including molecular tests, to detect fungi in clinical specimens are increasingly important in patient management and are becoming more reliable as technology improves. Molecular methods can also be used for detection of target gene mutations or other mechanisms that predict antifungal drug resistance. This review addresses acquired antifungal drug resistance in the principal human fungal pathogens and describes known resistance mechanisms and what in-house and commercial tools are available for their detection. It is emphasized that this approach should be complementary to culture-based susceptibility testing, given the range of mutations, resistance mechanisms and target genes that may be present in clinical isolates, but may not be included in current molecular assays.
Limitations to photosynthesis in bryophytes: certainties and uncertainties regarding methodology
Authors: Perera-Castro Alicia V , Waterman Melinda J , Robinson Sharon A , Flexas Jaume
Published: May 2022

Bryophytes are the group of land plants with the lowest photosynthetic rates, which was considered to be a consequence of their higher anatomical CO2 diffusional limitation compared with tracheophytes. However, the most recent studies assessing limitations due to biochemistry and mesophyll conductance in bryophytes reveal discrepancies based on the methodology used. In this study, we compared data calculated from two different methodologies for estimating mesophyll conductance: variable J and the curve-fitting method. Although correlated, mesophyll conductance estimated by the curve-fitting method was on average 4-fold higher than the conductance obtained by the variable J method; a large enough difference to account for the scale of differences previously shown between the biochemical and diffusional limitations to photosynthesis. Biochemical limitations were predominant when the curve-fitting method was used. We also demonstrated that variations in bryophyte relative water content during measurements can also introduce errors in the estimation of mesophyll conductance, especially for samples which are overly desiccated. Furthermore, total chlorophyll concentration and soluble proteins were significantly lower in bryophytes than in tracheophytes, and the percentage of proteins quantified as Rubisco was also significantly lower in bryophytes (<6.3% in all studied species) than in angiosperms (>16% in all non-stressed cases). Photosynthetic rates normalized by Rubisco were not significantly different between bryophytes and angiosperms. Our data suggest that the biochemical limitation to photosynthesis in bryophytes is more relevant than so far assumed.
Post-translational regulation of metabolic checkpoints in plant tetrapyrrole biosynthesis
Authors: Wang Peng , Ji Shuiling , Grimm Bernhard
Published: May 2022

Tetrapyrrole biosynthesis produces metabolites that are essential for critical reactions in photosynthetic organisms, including chlorophylls, heme, siroheme, phytochromobilins, and their derivatives. Due to the paramount importance of tetrapyrroles, a better understanding of the complex regulation of tetrapyrrole biosynthesis promises to improve plant productivity in the context of global climate change. Tetrapyrrole biosynthesis is known to be controlled at multiple levels—transcriptional, translational and post-translational. This review addresses recent advances in our knowledge of the post-translational regulation of tetrapyrrole biosynthesis and summarizes the regulatory functions of the various auxiliary factors involved. Intriguingly, the post-translational network features three prominent metabolic checkpoints, located at the steps of (i) 5-aminolevulinic acid synthesis (the rate-limiting step in the pathway), (ii) the branchpoint between chlorophyll and heme synthesis, and (iii) the light-dependent enzyme protochlorophyllide oxidoreductase. The regulation of protein stability, enzymatic activity, and the spatial organization of the committed enzymes in these three steps ensures the appropriate flow of metabolites through the tetrapyrrole biosynthesis pathway during photoperiodic growth. In addition, we offer perspectives on currently open questions for future research on tetrapyrrole biosynthesis.
Searching for flaring star–planet interactions in AU Mic TESS observations
Authors: Ilin E , Poppenhaeger K
Published: May 2022

Planets that closely orbit magnetically active stars are thought to be able to interact with their magnetic fields in a way that modulates stellar activity. This modulation in phase with the planetary orbit, such as enhanced X-ray activity, chromospheric spots, radio emission, or flares, is considered the clearest sign of magnetic star–planet interaction (SPI). However, the magnitude of this interaction is poorly constrained, and the intermittent nature of the interaction is a challenge for observers. AU Mic is an early M dwarf, and the most actively flaring planet host detected to date. Its innermost companion, AU Mic b, is a promising target for magnetic SPI observations. We used optical light curves of AU Mic obtained by the Transiting Exoplanet Survey Satellite to search for signs of flaring SPI with AU Mic b using a customized Anderson–Darling test. In the about 50 d of observations, the flare distributions with orbital, rotational, and synodic periods were generally consistent with intrinsic stellar flaring. We found the strongest deviation (p = 0.07, n = 71) from intrinsic flaring with the orbital period of AU Mic b, in the high-energy half of our sample (ED > 1 s). If it reflects the true SPI signal from AU Mic b, extending the observing time by a factor of 2–3 will yield a >3σ detection. Continued monitoring of AU Mic may therefore reveal flaring SPI with orbital phase, while rotational modulation will smear out due to the star’s strong differential rotation.
Radio masers on WX UMa: hints of a Neptune-sized planet, or magnetospheric reconnection?
Authors: Kavanagh Robert D , Vidotto Aline A , Vedantham Harish K , Jardine Moira M , Callingham Joe R , Morin Julien
Published: May 2022

The nearby M dwarf WX UMa has recently been detected at radio wavelengths with LOFAR. The combination of its observed brightness temperature and circular polarization fraction suggests that the emission is generated via the electron–cyclotron maser instability. Two distinct mechanisms have been proposed to power such emission from low-mass stars: either a sub-Alfvénic interaction between the stellar magnetic field and an orbiting planet, or reconnection at the edge of the stellar magnetosphere. In this paper, we investigate the feasibility of both mechanisms, utilizing the information about the star’s surrounding plasma environment obtained from modelling its stellar wind. Using this information, we show that a Neptune-sized exoplanet with a magnetic field strength of 10–100 G orbiting at ∼0.034 au can accurately reproduce the observed radio emission from the star, with a corresponding orbital period of 7.4 d. Due to the stellar inclination, a planet in an equatorial orbit is unlikely to transit the star. While such a planet could induce radial velocity semi-amplitudes from 7 to 396 m s−1, it is unlikely that this signal could be detected with current techniques due to the activity of the host star. The application of our planet-induced radio emission model here illustrates its exciting potential as a new tool for identifying planet-hosting candidates from long-term radio monitoring. We also develop a model to investigate the reconnection-powered emission scenario. While this approach produces less favourable results than the planet-induced scenario, it nevertheless serves as a potential alternative emission mechanism which is worth exploring further.
Impact of radial truncation on global 2D hydrodynamic simulations for a Sun-like model
Authors: Vlaykov D G , Baraffe I , Constantino T , Goffrey T , Guillet T , Le Saux A , Morison A , Pratt J
Published: May 2022

Stellar convection is a non-local process responsible for the transport of heat and chemical species. It can lead to enhanced mixing through convective overshooting and excitation of internal gravity waves (IGWs) at convective boundaries. The relationship between these processes is still not well understood and requires global hydrodynamic simulations to capture the important large-scale dynamics. The steep stratification in stellar interiors suggests that the radial extent of such simulations can affect the convection dynamics, the IGWs in the stably stratified radiative zone, and the depth of the overshooting layer. We investigate these effects using 2D global simulations performed with the fully compressible stellar hydrodynamics code music. We compare eight different radial truncations of the same solar-like stellar model evolved over approximately 400 convective turnover times. We find that the location of the inner boundary has an insignificant effect on the convection dynamics, the convective overshooting, and the travelling IGWs. We relate this to the background conditions at the lower convective boundary which are unaffected by the truncation, as long as a significantly deep radiative layer is included in the simulation domain. However, we find that extending the outer boundary by only a few per cent of the stellar radius significantly increases the velocity and temperature perturbations in the convection zone, the overshooting depth, the power and the spectral slope of the IGWs. The effect is related to the background conditions at the outer boundary, which are determined in essence by the hydrostatic stratification and the given luminosity.
The roles of ADAMDEC1 in trophoblast differentiation during normal pregnancy and preeclampsia
Authors: Li Zhuo-Hang , Li Xia , Li Fang-Fang , Wu Zhi-Hong , Xie You-Long , Zhang Shuang , Chen Xue-Mei , Wang Ying-Xiong , Ding Yu-Bin , Liu Tai-Hang
Published: May 2022

Human cytotrophoblast (CTB) differentiation into syncytiotrophoblast (STB) is essential for placental formation and function. Understanding the molecular mechanisms involved in trophoblast differentiation is necessary as it would help in the development of novel therapeutic agents to treat placentation-mediated pregnancy complications. In this study, we found a common upregulated gene, ADAM-like Decysin-1 (ADAMDEC1), from five published microarray and RNA-sequencing datasets. Interference to ADAMDEC1 impaired forskolin-induced BeWo cells differentiation, while ADAMDEC1 overexpression promoted BeWo cells and 3D JEG-3 spheroids differentiation. Interestingly, ADAMDEC1 may inhibit Thrombospondin 1 rather than E-cadherin to trigger the activation of the cAMP signal pathway during CTB differentiation into STB. More importantly, a decreasing in ADAMDEC1 might be involved in the development of preeclampsia. Therefore, ADAMDEC1 is expected to become a new target for prediction of and intervention in placenta-derived pregnancy diseases.
Novel eGZ-motif formed by regularly extruded guanine bases in a left-handed Z-DNA helix as a major motif behind CGG trinucleotide repeats
Authors: Fakharzadeh Ashkan , Zhang Jiahui , Roland Christopher , Sagui Celeste
Published: May 2022

The expansion of d(CGG) trinucleotide repeats (TRs) lies behind several important neurodegenerative diseases. Atypical DNA secondary structures have been shown to trigger TR expansion: their characterization is important for a molecular understanding of TR disease. CD spectroscopy experiments in the last decade have unequivocally demonstrated that CGG runs adopt a left-handed Z-DNA conformation, whose features remain uncertain because it entails accommodating GG mismatches. In order to find this missing motif, we have carried out molecular dynamics (MD) simulations to explore all the possible Z-DNA helices that potentially form after the transition from B- to Z-DNA. Such helices combine either CpG or GpC Watson-Crick steps in Z-DNA form with GG-mismatch conformations set as either intrahelical or extrahelical; and participating in BZ or ZZ junctions or in alternately extruded conformations. Characterization of the stability and structural features (especially overall left-handedness, higher-temperature and steered MD simulations) identified two novel Z-DNA helices: the most stable one displays alternately extruded Gs, and is followed by a helix with symmetrically extruded ZZ junctions. The G-extrusion favors a seamless stacking of the Watson-Crick base pairs; extruded Gs favor syn conformations and display hydrogen-bonding and stacking interactions. Such conformations could have the potential to hijack the MMR complex, thus triggering further expansion.
FABIAN-variant: predicting the effects of DNA variants on transcription factor binding
Authors: Steinhaus Robin , Robinson Peter N , Seelow Dominik
Published: May 2022

While great advances in predicting the effects of coding variants have been made, the assessment of non-coding variants remains challenging. This is especially problematic for variants within promoter regions which can lead to over-expression of a gene or reduce or even abolish its expression. The binding of transcription factors to the DNA can be predicted using position weight matrices (PWMs). More recently, transcription factor flexible models (TFFMs) have been introduced and shown to be more accurate than PWMs. TFFMs are based on hidden Markov models and can account for complex positional dependencies. Our new web-based application FABIAN-variant uses 1224 TFFMs and 3790 PWMs to predict whether and to which degree DNA variants affect the binding of 1387 different human transcription factors. For each variant and transcription factor, the software combines the results of different models for a final prediction of the resulting binding-affinity change. The software is written in C++ for speed but variants can be entered through a web interface. Alternatively, a VCF file can be uploaded to assess variants identified by high-throughput sequencing. The search can be restricted to variants in the vicinity of candidate genes. FABIAN-variant is available freely at https://www.genecascade.org/fabian/.
PADLOC: a web server for the identification of antiviral defence systems in microbial genomes
Authors: Payne Leighton J , Meaden Sean , Mestre Mario R , Palmer Chris , Toro Nicolás , Fineran Peter C , Jackson Simon A
Published: May 2022

Most bacteria and archaea possess multiple antiviral defence systems that protect against infection by phages, archaeal viruses and mobile genetic elements. Our understanding of the diversity of defence systems has increased greatly in the last few years, and many more systems likely await discovery. To identify defence-related genes, we recently developed the Prokaryotic Antiviral Defence LOCator (PADLOC) bioinformatics tool. To increase the accessibility of PADLOC, we describe here the PADLOC web server (freely available at https://padloc.otago.ac.nz), allowing users to analyse whole genomes, metagenomic contigs, plasmids, phages and archaeal viruses. The web server includes a more than 5-fold increase in defence system types detected (since the first release) and expanded functionality enabling detection of CRISPR arrays and retron ncRNAs. Here, we provide user information such as input options, description of the multiple outputs, limitations and considerations for interpretation of the results, and guidance for subsequent analyses. The PADLOC web server also houses a precomputed database of the defence systems in > 230,000 RefSeq genomes. These data reveal two taxa, Campylobacterota and Spriochaetota, with unusual defence system diversity and abundance. Overall, the PADLOC web server provides a convenient and accessible resource for the detection of antiviral defence systems.