bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequence tagging for biomedical extractive question answering
Authors: Yoon Wonjin , Jackson Richard , Lagerberg Aron , Kang Jaewoo
Published: June 2022

Motivation

Current studies in extractive question answering (EQA) have modeled the single-span extraction setting, where a single answer span is a label to predict for a given question-passage pair. This setting is natural for general domain EQA as the majority of the questions in the general domain can be answered with a single span. Following general domain EQA models, current biomedical EQA (BioEQA) models utilize the single-span extraction setting with post-processing steps.

Results

In this article, we investigate the question distribution across the general and biomedical domains and discover biomedical questions are more likely to require list-type answers (multiple answers) than factoid-type answers (single answer). This necessitates the models capable of producing multiple answers for a question. Based on this preliminary study, we propose a sequence tagging approach for BioEQA, which is a multi-span extraction setting. Our approach directly tackles questions with a variable number of phrases as their answer and can learn to decide the number of answers for a question from training data. Our experimental results on the BioASQ 7b and 8b list-type questions outperformed the best-performing existing models without requiring post-processing steps.

Availability and implementation

Source codes and resources are freely available for download at https://github.com/dmis-lab/SeqTagQA.

Supplementary information

Supplementary data are available at Bioinformatics online.
Separable expansions for covariance estimation via the partial inner product
Authors: Masak T , Sarkar S , Panaretos V M
Published: June 2022

The nonparametric estimation of covariance lies at the heart of functional data analysis, whether for curve or surface-valued data. The case of a two-dimensional domain poses both statistical and computational challenges, which are typically alleviated by assuming separability. However, separability is often questionable, sometimes even demonstrably inadequate. We propose a framework for the analysis of covariance operators of random surfaces that generalizes separability while retaining its major advantages. Our approach is based on the expansion of the covariance into a series of separable terms. The expansion is valid for any covariance over a two-dimensional domain. Leveraging the key notion of the partial inner product, we generalize the power iteration method to general Hilbert spaces, and show how the aforementioned expansion can be efficiently constructed in practice at the level of the surface observations. Truncation of the expansion and retention of the leading terms automatically induces a nonparametric estimator of the covariance, whose parsimony is dictated by the truncation level. The resulting estimator can be calculated, stored and manipulated with little computational overhead relative to separability. Consistency and rates of convergence are derived under mild regularity assumptions, illustrating the trade-off between bias and variance regulated by the truncation level. The merits and practical performance of the proposed methodology are demonstrated in a comprehensive simulation study.
Recurrent de novo mutations in CLDN5 induce an anion-selective blood–brain barrier and alternating hemiplegia
Authors: Hashimoto Yosuke , Poirier Karine , Boddaert Nathalie , Hubert Laurence , Aubart Melodie , Kaminska Anna , Alison Marianne , Desguerre Isabelle , Munnich Arnold , Campbell Matthew
Published: June 2022

Claudin-5 is the most enriched tight junction protein at the blood–brain barrier. Perturbations in its levels of expression have been observed across numerous neurological and neuropsychiatric conditions; however, pathogenic variants in the coding sequence of the gene have never been reported previously. Here, we report the identification of a novel de novo mutation (c.178G>A) in the CLDN5 gene in two unrelated cases of alternating hemiplegia with microcephaly. This mutation (G60R) lies within the first extracellular loop of claudin-5 and based on protein modelling and sequence alignment, we predicted it would modify claudin-5 to become an anion-selective junctional component as opposed to a purely barrier-forming protein.

Generation of stably transfected cell lines expressing wild-type or G60R claudin-5 showed that the tight junctions could still form in the presence of the G60R mutation but that the barrier against small molecules was clearly attenuated and displayed higher Cl− ion permeability and lower Na+ permeability.

While this study strongly suggests that CLDN5 associated alternating hemiplegia is a channelopathy, it is also the first study to identify the conversion of the blood–brain barrier to an anion-selective channel mediated by a dominant acting variant in CLDN5.
Vessel wall magnetic resonance and arterial spin labelling imaging in the management of presumed inflammatory intracranial arterial vasculopathy
Authors: Benjamin L A , Lim E , Sokolska M , Markus J , Zaletel T , Aggarwal V , Luder R , Sanchez E , Brown K , Sofat R , Singh A , Houlihan C , Nastouli E , Losseff N , Werring D J , Brown M M , Mason J C , Simister R J , Jäger H R
Published: June 2022

Optimal criteria for diagnosing and monitoring response to treatment for infectious and inflammatory medium–large vessel intracranial vasculitis presenting with stroke are lacking. We integrated intracranial vessel wall MRI with arterial spin labelling into our routine clinical stroke pathway to detect presumed inflammatory intracranial arterial vasculopathy, and monitor disease activity, in patients with clinical stroke syndromes. We used predefined standardized radiological criteria to define vessel wall enhancement, and all imaging findings were rated blinded to clinical details. Between 2017 and 2018, stroke or transient ischaemic attack patients were first screened in our vascular radiology meeting and followed up in a dedicated specialist stroke clinic if a diagnosis of medium–large inflammatory intracranial arterial vasculopathy was radiologically confirmed. Treatment was determined and monitored by a multi-disciplinary team. In this case series, 11 patients were managed in this period from the cohort of young stroke presenters (<55 years). The median age was 36 years (interquartile range: 33,50), of which 8 of 11 (73%) were female. Two of 11 (18%) had herpes virus infection confirmed by viral nucleic acid in the cerebrospinal fluid. We showed improvement in cerebral perfusion at 1 year using an arterial spin labelling sequence in patients taking immunosuppressive therapy for >4 weeks compared with those not receiving therapy [6 (100%) versus 2 (40%) P = 0.026]. Our findings demonstrate the potential utility of vessel wall magnetic resonance with arterial spin labelling imaging in detecting and monitoring medium–large inflammatory intracranial arterial vasculopathy activity for patients presenting with stroke symptoms, limiting the need to progress to brain biopsy. Further systematic studies in unselected populations of stroke patients are needed to confirm our findings and establish the prevalence of medium–large artery wall inflammation.
Management of antithrombotic therapy in patients at high bleeding risk after percutaneous coronary intervention for acute coronary syndromes: a case report
Authors: Mahmood Hamid , Shahid Farhan , Egred Mohaned , Farag Mohamed
Published: June 2022

Background

Choosing antithrombotic therapy for patients at high bleeding risk, particularly those requiring long-term anticoagulant therapy, who have acute coronary syndromes (ACS) and/or undergoing percutaneous coronary intervention (PCI) is becoming increasingly complex.

Case summary

A 78-year-old women was hospitalized with chest pain and a diagnosis of non-ST-elevation ACS was made. It was decided that the patient should undergo coronary angiogram with a view for angioplasty. Subsequently, she underwent successful PCI to the left anterior descending artery. Shortly after PCI, she was noted to be in atrial fibrillation. Furthermore, she had per rectal bleeding and acute kidney injury, which were managed conservatively. Aspirin and ticagrelor were stopped and she was discharged on dual antithrombotic therapy with clopidogrel and apixaban.

Discussion

Available evidence, driven mainly from expert consensus documents, advocates a case-by-case comprehensive evaluation that integrates patient- and procedure-related factors to assess patients for thrombotic and bleeding tendencies to identify those who may gain most net clinical benefit of antithrombotic combination therapy. In general, if thrombotic drivers prevail, an augmented antithrombotic regime with a view for a longer duration should be planned, and if bleeding drivers prevail, a de-escalated regime with a view for a shorter duration should be sought.
Early Retirement and Social Class: A Health-Giving Choice for All?
Authors: Qvist Jeevitha Yogachandiran
Published: June 2022

Empirical evidence on the effect of the timing of retirement on post-retirement health is so far inconclusive regarding the causal nature of this relationship, and little is known about how the effect varies by social class. This paper uses birth cohort variation in incentives to postpone early retirement in an instrumental variable framework to estimate the causal effect of early retirement on post-retirement health as indicated by visits to general practitioners (GP) and mortality. Drawing on Danish administrative register data, results from instrumental variable regressions suggest that for men, the effect of early retirement at age 60 on GP visits is positive and short-term, if anything, as it reduces early retirees’ number of visits to the GP compared to men who retire later than at age 60. These effects, among men, are particularly driven by members of the skilled manual working class. For women, the results show no evidence of a health effect of early retirement on GP visits. Additionally, for mortality, the results provided no evidence of a health effect of early retirement, irrespective of social class and gender.
Family Background, Educational Qualifications, and Labour Market Attainment: Evidence from Danish Siblings
Authors: Karlson Kristian Bernt , Birkelund Jesper Fels
Published: June 2022

Previous studies on how family background affects labour market outcomes among offspring with similar formal educational qualifications are limited either by the way in which they measure family background or by the detail level by which they measure educational attainment. To address these limitations, we develop a comprehensive approach based on sibling similarities in labour market outcomes. Applying the approach to high-quality register data on all Danes born 1965–1971, we examine the direct effect––other than through extremely granular education measures––of all combined effects of family background on occupational status and wages. Our analyses show that fine-grained education measures account for more than 90 per cent of the total family background effect on occupational status, while for wages they account for merely three-quarters. Half of the direct effect on wages can be explained by sibling similarities in occupational attainment, suggesting that direct family background effects on wages operate equally within and between occupations. However, observed family background characteristics account only for a minor portion of the direct effect on wages, pointing to that family-based advantages in the labour Danish market result from largely unidentified family characteristics. We discuss different mechanisms that may account for this pattern of results.
Characterization of a gene cluster involved in Aspergillus fumigatus zwitterionic glycosphingolipid synthesis
Authors: Seegers Carla I I , Ramón Roth Isabel , Zarnovican Patricia , Buettner Falk F R , Routier Françoise H
Published: June 2022

The human pathogenic fungus Aspergillus fumigatus synthesizes the zwitterionic glycolipid Manα1,3Manα1,6GlcNα1,2IPC, named Af3c. Similar glycosphingolipids having a glucosamine (GlcN) linked in α1,2 to inositolphosphoceramide (IPC) as core structure have only been described in a few pathogenic fungi. Here, we describe an A. fumigatus cluster of 5 genes (AFUA_8G02040 to AFUA_8G02090) encoding proteins required for the glycan part of the glycosphingolipid Af3c. Besides the already characterized UDP-GlcNAc:IPC α1,2-N-acetylglucosaminyltransferase (GntA), the cluster encodes a putative UDP-GlcNAc transporter (NstA), a GlcNAc de-N-acetylase (GdaA), and 2 mannosyltransferases (OchC and ClpC). The function of these proteins was inferred from analysis of the glycolipids extracted from A. fumigatus strains deficient in one of the genes. Moreover, successive introduction of the genes encoding GntA, GdaA, OchC, and ClpC in the yeast Saccharomyces cerevisiae enabled the reconstitution of the Af3c biosynthetic pathway. Absence of Af3c slightly reduced the virulence of A. fumigatus in a Galleria mellonella infection model.
Integrated delivery of family planning and childhood immunization services: a qualitative study of factors influencing service responsiveness in Malawi
Authors: Hamon Jessie K , Kambanje Misozi , Pryor Shannon , Kaponda Alice S , Mwale Erick , Mayhew Susannah H , Webster Jayne , Burchett Helen E D
Published: June 2022

Evidence from several countries in sub-Saharan Africa suggests that the integration of family planning (FP) with childhood immunization services can help reduce the unmet need for FP among postpartum women without undermining the uptake of immunizations. However, the quality and responsiveness of FP services that are integrated with childhood immunizations remain understudied. A qualitative study was conducted in two districts of Malawi, which examined the factors influencing the responsiveness of FP services that were integrated with childhood immunizations in monthly public outreach clinics. Semi-structured interviews with clients (n = 23) and FP providers (n = 10) and a clinic audit were carried out in six clinics. Hardware (material) and software (relational) factors influencing service responsiveness were identified through thematic and framework analyses of interview transcripts, and clinic characteristics were summarized from the audit data to contextualize the qualitative findings. Overall, 13 factors were found to influence service responsiveness in terms of the ease of access, choice of provider, environment, service continuity, confidentiality, communication, dignity and FP counselling afforded to clients. Among these factors, hardware deficiencies, including the absence of a dedicated building for the provision of FP services and the lack of FP commodities in clinics, were perceived to negatively affect service responsiveness. Crucially, the providers’ use of their agency to alter the delivery of services was found to mitigate the negative effects of some hardware deficits on the ease of access, choice of provider, environment and confidentiality experienced by clients. This study contributes to an emerging recognition that providers can offset the effect of hardware deficiencies when services are integrated if they are afforded sufficient flexibility to make independent decisions. Consideration of software elements in the design and delivery of FP services that are integrated with childhood immunizations is therefore critical to optimize the responsiveness of these services.
Oxytocinergic Modulation of Stress-Associated Amygdala-Hippocampus Pathways in Humans Is Mediated by Serotonergic Mechanisms
Authors: Lan Chunmei , Liu Congcong , Li Keshuang , Zhao Zhiying , Yang Jiaxin , Ma Yina , Scheele Dirk , Yao Shuxia , Kendrick Keith M , Becker Benjamin
Published: June 2022

Background

The hypothalamic neuropeptide oxytocin (OXT) may exert anxiolytic and stress-reducing actions via modulatory effects on amygdala circuits. Animal models and initial findings in humans suggest that some of these effects are mediated by interactions with other neurotransmitter systems, in particular the serotonin (5-HT) system. Against this background, the present pharmacological resting-state functional magnetic resonance imaging study aimed to determine whether effects of OXT on stress-associated amygdala intrinsic networks are mediated by 5-HT.

Methods

We employed a randomized, placebo-controlled, double-blind parallel-group, pharmacological functional magnetic resonance imaging resting-state experiment with 4 treatment groups in n = 112 healthy male participants. Participants underwent a transient decrease in 5-HT signaling via acute tryptophan depletion (ATD) or a corresponding placebo-control protocol before the administration of intranasal OXT (24 IU) or placebo intranasal spray.

Results

OXT and 5-HT modulation exerted interactive effects on the coupling of the left amygdala with the ipsilateral hippocampus and adjacent midbrain. OXT increased intrinsic coupling in this pathway, whereas this effect of OXT was significantly attenuated during transiently decreased central serotonergic signaling induced via acute tryptophan depletion. In the absence of OXT or 5-HT modulation, this pathway showed a trend for an association with self-reported stress perception in everyday life. No interactive effects were observed for the right amygdala.

Conclusions

Together, the findings provide the first evidence, to our knowledge, that the effects of OXT on stress-associated amygdala-hippocampal-midbrain pathways are critically mediated by the 5-HT system in humans.
Seroepidemiological Reconstruction of Long-term Chikungunya Virus Circulation in Burkina Faso and Gabon
Authors: Lim Jacqueline Kyungah , Ridde Valery , Agnandji Selidji Todagbe , Lell Bertrand , Yaro Seydou , Yang Jae Seung , Hoinard Damien , Weaver Scott C , Vanhomwegen Jessica , Salje Henrik , Yoon In-Kyu
Published: June 2022

Chikungunya virus (CHIKV) is a major public health concern worldwide. However, infection levels are rarely known, especially in Africa. We recruited individuals from Ouagadougou, Burkina Faso and Lambaréné, Gabon (age range, 1–55 years), tested their blood for CHIKV antibodies, and used serocatalytic models to reconstruct epidemiological histories. In Ouagadougou, 291 of 999 (29.1%) individuals were seropositive, ranging from 2% among those aged <10 years to 66% in those aged 40–55 years. We estimated there were 7 outbreaks since the 1970s but none since 2001, resulting in 600 000 infections in the city, none of which were reported. However, we could not definitively conclude whether infections were due to CHIKV or o’nyong-nyong, another alphavirus. In Lambaréné, 117 of 427 (27%) participants were seropositive. Our model identified a single outbreak sometime since 2007, consistent with the only reported CHIKV outbreak in the country. These findings suggest sporadic outbreaks in these settings and that the burden remains undetected or incorrectly attributed.
Fighting a Plague: Doctors' Stories of Challenge and Innovation Combatting the AIDS Epidemic in 1980s New York City
Authors: DeVita Timothy N
Published: June 2022

The human immunodeficiency virus (HIV) has devastated the United States for forty years. Though there are highly effective treatments for HIV and acquired immune deficiency syndrome (AIDS) today, the early years of the HIV/AIDS epidemic in New York City (NYC) were filled with uncertainty, fear, and death—not unlike the period we are now experiencing in the COVID-19 era. Existing scholarship captures the political discourse of the HIV/AIDS era and the narratives of physicians who specialized in HIV medicine. This essay uses eight in-depth interviews of physicians of various specialties who worked in NYC to understand the uncertainties and fears in daily work during the early AIDS epidemic. Their stories provide unique perspectives into the realities of working as physicians in the epicenter of a highly politicized epidemic with limited support, information, and treatments. They illustrate that HIV/AIDS provided unique biomedical, social, and political challenges to the physicians working in NYC during the 1980s. Over the course of the decade, these physicians adapted to meet challenges using methods that have since become commonplace in their clinical practice.
Real-time scanning electron microscopy of unfixed tissue in the solution using a deformable and electron-transmissive film
Authors: Shintani Seine A , Yamaguchi Seiji , Takadama Hiroaki
Published: June 2022

It is difficult to use scanning electron microscopy to observe the structure and movement of biological tissue immersed in the solution. To enable such observations, we created a highly deformable and electron-transmissive polyimide film that can withstand the pressure difference between the high-vacuum electron column and the atmospheric-pressure sample chamber. With this film, we used scanning electron microscopy to measure the intrinsic fine structure and movement of the contractile fibers of excised mouse heart immersed in physiological solutions. Our measurements revealed that the excised heart is a dynamic tissue that undergoes relaxation oscillation based on a three-dimensional force balance.
Selection and Appointment in International Adjudication: Insights from Political Science
Authors: Larsson Olof , Squatrito Theresa , Stiansen Øyvind , St John Taylor
Published: June 2022

This article summarizes insights from political science and empirical legal scholarship concerning selection and appointment of adjudicators to permanent international courts (ICs). This scholarship suggests that designers of ICs face challenging trade-offs in balancing judicial independence and accountability, as well as in promoting descriptive representation and necessary qualifications on the bench. The article considers different institutional design features related to appointment procedures: representation, reappointment, screening procedures and procedures for removing judges. Representation is discussed in a series of sections considering full or selective representation, voting rules and geographic and gender quotas and aspirational targets. Throughout, we draw on data on 24 ICs to illustrate the different appointment procedures and institutional features.
Refugee Participation through Representative Committees: UNHCR and the Sudanese Committee in Beirut
Authors: Janmyr Maja
Published: June 2022

The notions of refugee participation and empowerment are core—but highly debated and poorly implemented—standards of humanitarian response. Drawing on empirical research in Lebanon, this article offers an account of the ways in which—and which not—meaningful refugee participation and empowerment are achieved through representative committees. Spotlighting the case of the United Nations High Commissioner for Refugees (UNHCR)-supported Sudanese refugee committee in Beirut 2014–2015, it focuses on three intricate and interrelated concerns—refugee participation, representation, and autonomy. The article finds that the design and function of the committee made it difficult for refugees to share authority with UNHCR over decisions that impact their lives. The committee was primarily seen by UNHCR as a good in and of itself rather than as an opportunity to actively involve refugees in decision-making processes. The article suggests that there is ample room for the development of more meaningful participation that better integrates the capabilities, preferences, and agencies of persons living as refugees.
Axillary intra-aortic balloon pump, biventricular assist device implantation and subsequent orthotopic heart transplantation in a patient with sickle cell trait
Authors: Taylor Marcus , Mouyer Zakariya , Callan Paul , Shaw Steve , Venkateswaran Rajamiyer , Nwaejike Nnamdi
Published: June 2022

A 38-year-old male with sickle cell trait and acute refractory heart failure received an axillary intra-aortic balloon pump and short-term biventricular assist device. He underwent orthotopic heart transplantation 45 days later, which was complicated by major bleeding necessitating significant intra-operative transfusion. Support with veno-arterial extracorporeal membrane oxygenation was provided and successfully weaned five days later. He made a full recovery and remains alive and well 34 months after discharge. We hypothesize that the protective peri-operative measures undertaken, including normothermia during surgery and post-operative haemodynamic stability due to the use of mechanical circulatory support, conveyed a degree of protection against complications associated with sickle cell dysfunction and contributed to the successful outcome.
Application of the Fluorescence Method on Sysmex XN9000 Hematology Analyzer for Correcting Platelet Count in Individuals with Microcytosis
Authors: Deng Jiankai , Xie Shuhua , Chen Yaoming , Ma Qinghua , He Yuting , Liu Min , Wang Dong , Yu Xuegao
Published: June 2022

Objective

Although small red blood cells are a well-known analytical pitfall that could cause artifactual increase of the platelet count, limited information is available on the accuracy of impedance platelet counting in cases with microcytosis. The aim of this study is to assess the accuracy of impedance platelet counting in the presence of small red blood cells, and to establish the optimal mean corpuscular volume (MCV) cutoff to endorse fluorescence platelet counting.

Methods

In this study, platelet counts estimated by the impedance method on the Sysmex XN9000 analyzer (Sysmex, Kobe, Japan) were compared with those provided by the fluorescence method. The accuracy of impedance platelet counting was assessed. Receiver operating characteristic curve was used to evaluate the performance of MCV in predicting falsely increased platelet counts.

Results

There was a tendency for the impedance method to overestimate the platelet count in samples with 70 fL < MCV ≤ 80 fL, 60 fL < MCV ≤ 70 fL, MCV ≤ 60 fL. Receiver operating characteristic curve analysis showed that a 73.5fL cutoff of MCV was highly sensitive in predicting falsely increased platelet counts.

Conclusion

In cases with MCV < 73.5 fL, we strongly suggest that the platelet counts obtained by the impedance method on the Sysmex XN9000 analyzer should be checked and corrected by fluorescence counting.
Aspergillosis in a colony of Humboldt penguins (Spheniscus humboldti) under managed care: a clinical and environmental investigation in a French zoological park
Authors: Cateau Estelle , Leclerc Antoine , Cartier Noémie , Valsecchi Isabel , Bailly Éric , Le Senechal Ronan , Becerra Margaux , Le Gallou Brice , Lavergne Rose-Anne , Chesnay Adélaïde , Robin Jean-Patrice , Cray Carolyn , Goddard Nicolas , Thorel Milan , Guillot Jacques , Mulot Baptiste , Desoubeaux Guillaume
Published: June 2022

Aspergillosis is pervasive in bird populations, especially those under human care. Its management can be critically impacted by exposure to high levels of conidia and by resistance to azole drugs. The fungal contamination in the environment of a Humboldt penguin (Spheniscus humboldti) group, housed in a French zoological park next to numerous large crop fields, was assessed through three serial sessions of surface sampling in nests, in 2018–20: all isolates were counted and characterized by sequencing. When identified as Aspergillus fumigatus, they were systematically screened for resistance mutations in the cyp51A gene and tested for minimal inhibitory concentrations (MICs) determination. At the same time, the clinical incidence of aspergillosis was evaluated in the penguin population by the means of systematic necropsy and mycological investigations. A microsatellite-based analysis tracked the circulation of A. fumigatus strains. Environmental investigations highlighted the substantial increase of the fungal load during the summer season (>12-fold vs. the other timepoints) and a large overrepresentation of species belonging to the Aspergillus section Fumigati, ranging from 22.7 to 94.6% relative prevalence. Only one cryptic species was detected (A. nishimurae), and one isolate exhibited G138S resistance mutation with elevated MICs. The overall incidence of aspergillosis was measured at ∼3.4% case-years, and mostly in juveniles. The analysis of microsatellite polymorphism revealed a high level of genetic diversity among A. fumigatus clinical isolates. In contrast, one environmental strain appeared largely overrepresented during the summer sampling session. In all, the rural location of the zoo did not influence the emergence of resistant strains.

Lay summary
Resonant shattering flares in black hole-neutron star and binary neutron star mergers
Authors: Neill Duncan , Tsang David , van Eerten Hendrik , Ryan Geoffrey , Newton William G
Published: June 2022

Resonant shattering flares (RSFs) are bursts of gamma-rays expected to be triggered by tidal resonance of a neutron star (NS) during binary inspiral. They are strongly dependent on the magnetic field strength at the surface of the NS. By modelling these flares as being the result of multiple colliding relativistic shells launched during the resonance window, we find that the prompt non-thermal gamma-ray emission may have luminosity up to a few $\times 10^{48}\rm{ erg\,s}^{-1}$, and that a broad-band afterglow could be produced. We compute the expected rates of detectable RSFs using the BPASS population synthesis code, with different assumptions about the evolution of surface magnetic field strengths before merger. We find the rate of detectable RSFs to be ∼0.0001–5 per year for BHNS mergers and ∼0.0005–25 per year for NSNS mergers, with the lower bound corresponding to surface-field decay consistent with magneto-thermal evolution in purely crustal fields, while the upper bounds are for systems that have longer lived surface magnetic fields supported by flux frozen into the superconducting core. If some of the observed SGRB precursor flares are indeed RSFs, this suggests the presence of a longer lived surface field for some fraction of the NS population, and that we could expect RSFs to be the most common detectable EM counterpart to GW detections of BHNS mergers. The non-detection of an RSF prior to GRB170817A provides an upper bound on the magnetic fields of the progenitor NSs of Bsurf ∼ 1013.5G.
Why are we still using 3D masses for cluster cosmology?
Authors: Debackere Stijn N B , Hoekstra Henk , Schaye Joop , Heitmann Katrin , Habib Salman
Published: June 2022

The abundance of clusters of galaxies is highly sensitive to the late-time evolution of the matter distribution, since clusters form at the highest density peaks. However, the 3D cluster mass cannot be inferred without deprojecting the observations, introducing model-dependent biases and uncertainties due to the mismatch between the assumed and the true cluster density profile and the neglected matter along the sightline. Since projected aperture masses can be measured directly in simulations and observationally through weak lensing, we argue that they are better suited for cluster cosmology. Using the Mira–Titan suite of gravity-only simulations, we show that aperture masses correlate strongly with 3D halo masses, albeit with large intrinsic scatter due to the varying matter distribution along the sightline. Nonetheless, aperture masses can be measured ≈2–3 times more precisely from observations, since they do not require assumptions about the density profile and are only affected by the shape noise in the weak lensing measurements. We emulate the cosmology dependence of the aperture mass function directly with a Gaussian process. Comparing the cosmology sensitivity of the aperture mass function and the 3D halo mass function for a fixed survey solid angle and redshift interval, we find the aperture mass sensitivity is higher for Ωm and $w_a$, similar for σ8, ns, and $w_0$, and slightly lower for h. With a carefully calibrated aperture mass function emulator, cluster cosmology analyses can use cluster aperture masses directly, reducing the sensitivity to model-dependent mass calibration biases and uncertainties.
Explaining prolonged fluctuations in light curves of classical novae via modelling
Authors: Hillman Yael
Published: June 2022

Fluctuations during a prolonged maximum have been observed in several nova eruptions, although it is not clear, and cannot be deduced directly from observations, whether the phenomenon is an actual physical reaction to some mechanism originating in the erupting white dwarf, whether it is occurring in the expanding ejected shell, or whether it is a form of interaction with the red dwarf companion. A handful of erupting nova models are investigated in this work, in order to assess the possibility of this sort of feature being an actual part of the eruption itself. The results explain that the mechanism that may produce these fluctuations is the repeated approach and recession of the convective front from the surface. The efficiency of this mechanism, being dependent on the mass of the WD (white dwarf) envelope and the time-scale of the nova cycle, favours low-mass WDs and long accretion phases.
Investigation of stellar magnetic activity using variational autoencoder based on low-resolution spectroscopic survey
Authors: Xiang Yue , Gu Shenghong , Cao Dongtao
Published: June 2022

We apply the variational autoencoder (VAE) to the LAMOST-K2 low-resolution spectra to detect the magnetic activity of the stars in the K2 field. After the training on the spectra of the selected inactive stars, the VAE model can efficiently generate the synthetic reference templates needed by the spectral subtraction procedure, without knowing any stellar parameters. Then, we detect the peculiar spectral features, such as chromospheric emissions, strong nebular emissions, and lithium absorptions, in our sample. We measure the emissions of the chromospheric activity indicators, Hα and Ca ii infrared triplet (IRT) lines, to quantify the stellar magnetic activity. The excess emissions of Hα and Ca ii IRT lines of the active stars are correlated well to the rotational periods and the amplitudes of light curves derived from the K2 photometry. We degrade the LAMOST spectra to simulate the slitless spectra of the China Space Station Telescope (CSST) and apply the VAE to the simulated data. For cool active stars, we reveal a good agreement between the equivalent widths of Hα line derived from the spectra with two resolutions. The result indicates the ability of identifying the magnetically active stars in the future CSST survey, which will deliver an unprecedented large data base of low-resolution spectra as well as simultaneous multiband photometry of stars.
MOCCA-survey data base: extra galactic globular clusters – II. Milky Way and Andromeda
Authors: Leveque A , Giersz M , Arca-Sedda M , Askar Abbas
Published: June 2022

A comprehensive study of the co-evolution of globular cluster systems (GCS) in galaxies requires the ability to model both the large-scale dynamics (0.01–10 kpc) regulating their orbital evolution, and the small-scale dynamics (sub-pc – au) regulating the internal dynamics of each globular cluster (GC). In this work, we present a novel method that combine semi-analytic models of GCS with fully self-consistent Monte Carlo models to simultaneously evolve large GCSs. We use the population synthesis code MASinGa and the MOCCA-Survey Database I to create synthetic GC populations aimed at representing the observed features of GCs in the Milky Way (MW) and Andromeda (M31). Our procedure enables us to recover the spatial and mass distribution of GCs in such galaxies, and to constrain the amount of mass that GCs left either in the halo as dispersed debris, or in the galactic centre, where they can contribute to the formation of a nuclear star cluster (NSC) and can bring stellar and possibly intermediate mass black holes there. The final masses reported by our simulations are of a few order of magnitudes smaller than the observed values. These differences show that mass build-up of an NSC and central BHs in galaxies like MW and M31 cannot be solely explained by the infalling GC scenario. This build-up is likely to depend on the interplay between interactions and mergers of infalling GCs and gas. The latter can contribute to both in situ star formation in the NSC and growth of the central BH.
Human Follicular Mites: Ectoparasites Becoming Symbionts
Authors: Smith Gilbert , Manzano-Marín Alejandro , Reyes-Prieto Mariana , Antunes Cátia Sofia Ribeiro , Ashworth Victoria , Goselle Obed Nanjul , Jan Abdulhalem Abdulsamad A , Moya Andrés , Latorre Amparo , Perotti M Alejandra , Braig Henk R
Published: June 2022

Most humans carry mites in the hair follicles of their skin for their entire lives. Follicular mites are the only metazoans that continuously live on humans. We propose that Demodex folliculorum (Acari) represents a transitional stage from a host-injuring obligate parasite to an obligate symbiont. Here, we describe the profound impact of this transition on the genome and physiology of the mite. Genome sequencing revealed that the permanent host association of D. folliculorum led to an extensive genome reduction through relaxed selection and genetic drift, resulting in the smallest number of protein-coding genes yet identified among panarthropods. Confocal microscopy revealed that this gene loss coincided with an extreme reduction in the number of cells. Single uninucleate muscle cells are sufficient to operate each of the three segments that form each walking leg. While it has been assumed that the reduction of the cell number in parasites starts early in development, we identified a greater total number of cells in the last developmental stage (nymph) than in the terminal adult stage, suggesting that reduction starts at the adult or ultimate stage of development. This is the first evolutionary step in an arthropod species adopting a reductive, parasitic, or endosymbiotic lifestyle. Somatic nuclei show under-replication at the diploid stage. Novel eye structures or photoreceptors as well as a unique human host melatonin-guided day/night rhythm are proposed for the first time. The loss of DNA repair genes coupled with extreme endogamy might have set this mite species on an evolutionary dead-end trajectory.
A New Paradigm of Multiheme Cytochrome Evolution by Grafting and Pruning Protein Modules
Authors: Soares Ricardo , Costa Nazua L , Paquete Catarina M , Andreini Claudia , Louro Ricardo O
Published: June 2022

Multiheme cytochromes play key roles in diverse biogeochemical cycles, but understanding the origin and evolution of these proteins is a challenge due to their ancient origin and complex structure. Up until now, the evolution of multiheme cytochromes composed by multiple redox modules in a single polypeptide chain was proposed to occur by gene fusion events. In this context, the pentaheme nitrite reductase NrfA and the tetraheme cytochrome c554 were previously proposed to be at the origin of the extant octa- and nonaheme cytochrome c involved in metabolic pathways that contribute to the nitrogen, sulfur, and iron biogeochemical cycles by a gene fusion event. Here, we combine structural and character-based phylogenetic analysis with an unbiased root placement method to refine the evolutionary relationships between these multiheme cytochromes. The evidence show that NrfA and cytochrome c554 belong to different clades, which suggests that these two multiheme cytochromes are products of truncation of ancestral octaheme cytochromes related to extant octaheme nitrite reductase and MccA, respectively. From our phylogenetic analysis, the last common ancestor is predicted to be an octaheme cytochrome with nitrite reduction ability. Evolution from this octaheme framework led to the great diversity of extant multiheme cytochromes analyzed here by pruning and grafting of protein modules and hemes. By shedding light into the evolution of multiheme cytochromes that intervene in different biogeochemical cycles, this work contributes to our understanding about the interplay between biology and geochemistry across large time scales in the history of Earth.
Association of disease activity using SDAI and DAS28, but not JADAS-27, with subsequent changes in physical function in adult patients with juvenile idiopathic arthritis
Authors: Miyamae Takako , Inoue Eisuke , Tanaka Eiichi , Kawabe Tomohiro , Ikari Katsunori , Harigai Masayoshi
Published: June 2022

Objectives

To investigate an optimal composite score for disease activity in adult JIA from the viewpoint of the subsequent changes in physical function.

Methods

Patients with JIA under the following conditions were enrolled: 1) disease onset < 18 years; 2) registered in the database by Tokyo Women’s Medical University for the first time between 2000 and 2020; and 3) ≥18 years old at the time of registration. Patients were stratified according to mean disease activity scores in SDAI, DAS28, and JADAS-27 during the first year from baseline. Trends of estimated mean change in Japanese-HAQ score (ΔJ-HAQ) from baseline to 2 years later was examined across the stratified groups of each index.

Results

We included 294 eligible individuals (median age at onset, 14.0 years; RF positive in 64.7%). A significant increasing trend of the estimated mean ΔJ-HAQ at 2 years after baseline was observed along with an increase in the mean disease activity during the first year measured using DAS28 (p = 0.01) and SDAI (p = 0.018), but not using JADAS-27.

Conclusions

Disease activity measured using SDAI and DAS28, but not using JADAS27, was significantly associated with subsequent changes in physical function in adult patients with JIA.
Controllable assembly of synthetic constructs with programmable ternary DNA interaction
Authors: Cui Huangchen , Zhang Tianqing , Kong Yuhan , Xing Hang , Wei Bryan
Published: June 2022

Compared with the dual binding components in a binary interaction, the third component of a ternary interaction often serves as modulator or regulator in biochemical processes. Here, we presented a programmable ternary interaction strategy based on the natural DNA triplex structure. With the DNA triplex-based ternary interaction, we have successfully demonstrated controllable hierarchical assemblies from nanometer scale synthetic DNA nanostructure units to micrometer scale live bacteria. A selective signaling system responsive to orthogonal nucleic acid signals via ternary interaction was also demonstrated. This assembly method could further enrich the diversified design schemes of DNA nanotechnology.
Mechanism of lesion verification by the human XPD helicase in nucleotide excision repair
Authors: Fu Iwen , Mu Hong , Geacintov Nicholas E , Broyde Suse
Published: June 2022

In nucleotide excision repair (NER), the xeroderma pigmentosum D helicase (XPD) scans DNA searching for bulky lesions, stalls when encountering such damage to verify its presence, and allows repair to proceed. Structural studies have shown XPD bound to its single-stranded DNA substrate, but molecular and dynamic characterization of how XPD translocates on undamaged DNA and how it stalls to verify lesions remains poorly understood. Here, we have performed extensive all-atom MD simulations of human XPD bound to undamaged and damaged ssDNA, containing a mutagenic pyrimidine (6−4) pyrimidone UV photoproduct (6−4PP), near the XPD pore entrance. We characterize how XPD responds to the presence of the DNA lesion, delineating the atomistic-scale mechanism that it utilizes to discriminate between damaged and undamaged nucleotides. We identify key amino acid residues, including FeS residues R112, R196, H135, K128, Arch residues E377 and R380, and ATPase lobe 1 residues 215−221, that are involved in damage verification and show how movements of Arch and ATPase lobe 1 domains relative to the FeS domain modulate these interactions. These structural and dynamic molecular depictions of XPD helicase activity with unmodified DNA and its inhibition by the lesion elucidate how the lesion is verified by inducing XPD stalling.
Progesterone Increases Nicotine Withdrawal and Anxiety in Male but Not Female Smokers During Brief Abstinence
Authors: Novick Andrew M , Duffy Korrina A , Johnson Rachel L , Sammel Mary D , Cao Wen , Strasser Andrew A , Sofuoglu Mehmet , Kuzma Alexandra , Loughead James , Epperson C Neill
Published: June 2022

Introduction

Although exogenous progesterone may hold promise as a treatment for nicotine use disorders, it is unclear whether it is similarly effective in males and females. This study examined the effects of progesterone on nicotine use disorder comprehensively using behavioral, psychological, and neural measures in male and female smokers exposed to brief abstinence.

Aims and Methods

Thirty-three male and 33 female non-treatment-seeking smokers participated in a double-blind, randomized, placebo-controlled crossover study of 200 mg of progesterone or placebo daily over a four-day abstinence period. Smoking behavior and subjective effects of nicotine were assessed at baseline and after final drug administration. Nicotine withdrawal, smoking urges, mood states, and neural response to smoking cues were measured at baseline, after the first drug administration, and after the final drug administration.

Results

No main effect of drug (progesterone vs. placebo) emerged for any outcome. Significant sex by drug interactions emerged for nicotine withdrawal (p = .020), perceived strength of nicotine (p = .040), and perceived bad effects of nicotine (p = .029). Males receiving progesterone reported worse nicotine withdrawal (p = .046) and a trend towards decreased bad effects of nicotine (p = .070). Males on progesterone also reported greater tension and anxiety relative to placebo (p = .021). Females on progesterone perceived nicotine’s effects as being stronger relative to placebo (p = .046).

Conclusions

Progesterone causes sex-dependent effects on smoking-related outcomes during brief abstinence. Specifically, progesterone in males may increase rather than decrease nicotine withdrawal and negative affect during abstinence, potentially hindering efforts to quit smoking.

Implications

In male and female smokers undergoing a brief period of abstinence, we examined the effects of progesterone on smoking outcomes. While progesterone had limited effects in female smokers, in males, it worsened nicotine withdrawal and negative affect. Our findings emphasize the importance of analyzing sex differences in future studies examining progesterone as a potential treatment and suggest that progesterone in males could potentially exacerbate aspects of nicotine dependence.

Clinicaltrials.gov registration

NCT01954966. https://clinicaltrials.gov/ct2/show/NCT01954966