bluuebunny/crossref_metadata_2025 huggingface dataset:
The risk of acute coronary events in microvascular disease
Authors: Varrichione Giuseppe , Giuseppe Biccire’ Flavio , Di Pietro Riccardo , Prati Francesco , Battisti Paola
Published: November 2022

The microvascular disease represents a widespread clinical entity in the general population, especially among women. The dysfunction of the microcirculation is often responsible for myocardial ischaemia and angina in the absence of significant stenosis of the epicardial district, while in other cases it can represent a contributing cause of angina even in the presence of coronary artery disease, cardiomyopathies or heart failure. The cardiovascular risk factors of people with microvascular disease are similar to those who develop epicardial atherosclerotic disease. However, the prognostic significance of microvascular disease remains a matter of debate. An element to be clarified, in fact, is whether subjects with dysfunction of the microcirculation and coronary tree without significant stenoses present an increased risk of myocardial infarction and sudden death. In recent years, several studies seem to confirm an association between microvascular disease and progression of coronary epicardial atherosclerosis. The prognosis of microvascular disease would therefore not be benign as was previously believed, but associated with an increased risk of cardiovascular events including revascularization, heart attack, and cardiac death.
Empagliflozin in heart failure with preserved ejection fraction: first success in mission impossible
Authors: Sciatti Edoardo , Gori Mauro , D’elia Emilia , Iacovoni Attilio , Senni Michele
Published: November 2022

Heart failure and preserved ejection fraction (EF) is a common disease with a poor prognosis and increasing prevalence in the community. The current treatment paradigm includes symptomatic therapy, such as diuretics, risk factor control, and treatment of comorbidities. According to the most recent European guidelines, there is no effective therapy in patients with heart failure and left ventricular EF ≥50%, while the pharmacological compounds normally used in heart failure with reduced EF could also be implemented in patients with EF slightly reduced (between 40 and 50%), with a recommendation class IIB. The recently published Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved) study challenged current guidelines, showing for the first time in patients with heart failure and EF >40% better outcomes with the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin than with placebo. This result was consistent in patients with and without diabetes, as well as in those with EF below and above 50%. The purpose of the review is to describe the rationale for this important finding and the main results of the EMPEROR-Preserved study and to provide some suggestions for the daily clinical management of SGLT2 inhibitors.
On site cardiac surgery for structural heart interventions: a fence to mend?
Authors: Foglietta Melissa , Radico Francesco , Appignani Marianna , Aquilani Roberta , Di Fulvio Maria , Zimarino Marco
Published: November 2022

Current evidence supports device-based transcatheter interventions for the management of patients with structural heart disease, proving well their safety and efficacy; transcatheter aortic valve implantation (TAVI), transcatheter edge-to-edge repair (TEER) of mitral or tricuspid valves, and left atrial appendage occlusion (LAAO) are expanding their role in contemporary practice. Currently, guidelines recommend performing TAVI in ‘Heart Valve Center’ with interventional cardiology and institutional on-site cardiac surgery (iOSCS), while no site limitation has been defined for TEER and LAAO. The growing number of candidates for transcatheter interventions generates long waiting times with negative consequences on mortality, morbidity, hospitalization, and functional deterioration. Therefore, a debate on the feasibility of TAVI in centres without iOSCS has been set up. Data from randomized controlled trials and registries failed to document any difference in outcomes and in conversion rate to emergent surgical bailout in centres with or without iOSCS; on the other hand, a direct relationship with TAVI complications has been clearly documented for learning curve and centre volume. Therefore, the role of iOSCS for TAVI, as well as for other transcatheter interventions, should be carefully explored.
Repeatability of ventricular arrhythmia characteristics on the exercise-stress test in RYR2-mediated catecholaminergic polymorphic ventricular tachycardia
Authors: Peltenburg Puck J , Pultoo Sanjeev N J , Tobert Kathryn E , Bos J Martijn , Lieve Krystien V V , Tanck Michael , Clur Sally-Ann B , Blom Nico A , Ackerman Michael J , Wilde Arthur A M , van der Werf Christian
Published: November 2022

Aims

In catecholaminergic polymorphic ventricular tachycardia (CPVT), the exercise-stress test (EST) is the cornerstone for the diagnosis, risk stratification, and assessment of therapeutic efficacy, but its repeatability is unknown. We aimed to test the repeatability of ventricular arrhythmia characteristics on the EST in patients with CPVT.

Methods and results

EST-pairs (ESTs performed within 18 months between 2005 and 2021, on the same protocol, and without or on the exact same treatment) of patients with RYR2-mediated CPVT from two specialized centres were included. The primary endpoint was the repeatability of the maximum ventricular arrhythmia score [VAS: 0 for the absence of premature ventricular contractions (PVCs); 1 for isolated PVCs; 2 for bigeminal PVCs; 3 for couplets; and 4 for non-sustained ventricular tachycardia]. Secondary outcomes were the repeatability of the heart rate at the first PVC and the ΔVAS (the absolute difference in VAS between the EST-pairs). A total of 104 patients with 349 EST-pairs were included. The median duration between ESTs was 343 (interquartile range, 189–378) days. Sixty (17.2%) EST-pairs were off therapy. The repeatability of the VAS was moderate {Krippendorf α, 0.56 [95% confidence interval (CI), 0.48–0.64]}, and the repeatability of the heart rate at the first PVC was substantial [intra-class correlation coefficient, 0.78 (95% CI, 0.71–0.84)]. The use of medication was associated with a higher odds for a ΔVAS > 1 (odds ratio = 3.52; 95% CI, 2.46–4.57; P = 0.020).

Conclusion

The repeatability of ventricular arrhythmia characteristics was moderate to substantial. This underlines the need for multiple ESTs in CPVT patients and CPVT suspicious patients and it provides the framework for assessing the therapeutic efficacy of novel CPVT therapies.
Functional microbial ecology in arctic soils: the need for a year-round perspective
Authors: Poppeliers Sanne W M , Hefting Mariet , Dorrepaal Ellen , Weedon James T
Published: November 2022

The microbial ecology of arctic and sub-arctic soils is an important aspect of the global carbon cycle, due to the sensitivity of the large soil carbon stocks to ongoing climate warming. These regions are characterized by strong climatic seasonality, but the emphasis of most studies on the short vegetation growing season could potentially limit our ability to predict year-round ecosystem functions. We compiled a database of studies from arctic, subarctic, and boreal environments that include sampling of microbial community and functions outside the growing season. We found that for studies comparing across seasons, in most environments, microbial biomass and community composition vary intra-annually, with the spring thaw period often identified by researchers as the most dynamic time of year. This seasonality of microbial communities will have consequences for predictions of ecosystem function under climate change if it results in: seasonality in process kinetics of microbe-mediated functions; intra-annual variation in the importance of different (a)biotic drivers; and/or potential temporal asynchrony between climate change-related perturbations and their corresponding effects. Future research should focus on (i) sampling throughout the entire year; (ii) linking these multi-season measures of microbial community composition with corresponding functional or physiological measurements to elucidate the temporal dynamics of the links between them; and (iii) identifying dominant biotic and abiotic drivers of intra-annual variation in different ecological contexts.
Akkermansia muciniphilaattenuates LPS-induced acute kidney injury by inhibiting TLR4/NF-κB pathway
Authors: Shi Jun , Wang Feng , Tang Lei , Li Zhiqiang , Yu Manshu , Bai Yu , Weng Zebin , Sheng Meixiao , He Weiming , Chen Yugen
Published: November 2022

Acute kidney injury (AKI) is a global public health hazard with high morbidity and mortality. Sepsis accounts for nearly half of all causes of AKI. Scientists have made a great effort to explore effective therapeutic agents with limited side effects in the treatment of AKI, but have had little success. With the development of gut flora study, Akkermansia muciniphila (A. muciniphila) has been proven to prevent different organs by regulating the inflammatory response. However, the reno-protective function is still unknown. Here, the AKI model was induced using lipopolysaccharide (LPS) in mice with or without pretreatment of A. muciniphila. Renal function and histological change were measured. Inflammatory factors were detected by ELISA and rt-PCR. TLR4/NF-κB signaling factors and NLRP3 inflammasome were tested by western blot and immunohistochemistry. Pretreatment of A. muciniphila markedly inhibited inflammatory response and ameliorated kidney histopathological changes. Furthermore, the TLR4, p-NF-κB p65, and downstream IκBα were notably activated in the model group and inhibited by A. muciniphila. A similar effect was found in the regulation of NLRP3 inflammasome. In conclusion, pretreatment with A. muciniphila could protect against LPS-induced AKI by inhibition of the TLR4/NF-κB pathway and NLRP3 inflammasome activation. It may be a new therapeutic strategy for AKI prevention and treatment in the future.
The ribosome rescue pathways SsrA-SmpB, ArfA, and ArfB mediate tolerance to heat and antibiotic stresses in Azotobacter vinelandii
Authors: Moreno Soledad , Muriel-Millán Luis Felipe , Rodríguez-Martínez Karen , Ortíz-Vasco Cristian , Bedoya-Pérez Leidy Patricia , Espín Guadalupe
Published: November 2022

Bacteria have a mechanism to rescue stalled ribosomes known as trans-translation consisting of SsrA, a transfer-messenger RNA (tmRNA), and the small protein SmpB. Other alternative rescue mechanisms mediated by ArfA and ArfB proteins are present only in some species. Ribosome rescue mechanisms also play a role in tolerance to antibiotics and various stresses such as heat. This study shows that the genome of the soil bacterium A. vinelandii harbours genes encoding for tmRNA, SmpB, two paralogs of ArfA (arfA1 and arfA2), and ArfB. A number of mutant strains carrying mutations in the ssrA, arfA1, arfA2, and arfB genes were constructed and tested for their growth and susceptibility to heat and the antibiotic tetracycline. We found that the inactivation of both ssrA and one or the two arfA genes was detrimental to growth and caused a higher susceptibility to heat and to the antibiotic tetracycline. Interestingly, the arfB mutant strain was unable to grow after 2 h of incubation at 45°C. Inactivation of arfB in the ssrA-arfA1-arfA2 strain caused a lethal phenotype since the quadruple mutant could not be isolated. Taken together, our data suggest that both arfA1 and arfA2, as well as arfB, are functional as back up mechanisms, and that the ArfB pathway has an essential role that confers A. vinelandii resistance to high temperatures.
Structural remodeling of SARS-CoV-2 spike protein glycans reveals the regulatory roles in receptor-binding affinity
Authors: Hsu Yen-Pang , Frank Martin , Mukherjee Debopreeti , Shchurik Vladimir , Makarov Alexey , Mann Benjamin F
Published: November 2022

Glycans of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein are speculated to play functional roles in the infection processes as they extensively cover the protein surface and are highly conserved across the variants. The spike protein has been the principal target for vaccine and therapeutic development while the exact effects of its glycosylation remain elusive. Analytical reports have described the glycan heterogeneity of the spike protein. Subsequent molecular simulation studies provided a knowledge basis of the glycan functions. However, experimental data on the role of discrete glycoforms on the spike protein pathobiology remains scarce. Building an understanding of their roles in SARS-CoV-2 is important as we continue to develop effective medicines and vaccines to combat the disease. Herein, we used designed combinations of glycoengineering enzymes to simplify and control the glycosylation profile of the spike protein receptor-binding domain (RBD). Measurements of the receptor-binding affinity revealed opposite regulatory effects of the RBD glycans with and without sialylation, which presents a potential strategy for modulating the spike protein behaviors through glycoengineering. Moreover, we found that the reported anti-SARS-CoV-(2) antibody, S309, neutralizes the impact of different RBD glycoforms on the receptor-binding affinity. In combination with molecular dynamics simulation, this work reports the regulatory roles that glycosylation plays in the interaction between the viral spike protein and host receptor, providing new insights into the nature of SARS-CoV-2. Beyond this study, enzymatic glycan remodeling offers the opportunity to understand the fundamental role of specific glycoforms on glycoconjugates across molecular biology.
UK High Court Decides on Infringement of EPC 2000 Claims Based on German Patent Law
Authors: Rainsford Edward , Kaufmann Ulrike
Published: November 2022

In recent years various German courts have ruled on the scope of protection and infringement of second medical use patents. Due to a special contractual clause, the UK High Court now had to deal with the development of this German case law in the context of a patent licence dispute, taking into account the unusual feature that the subject of the dispute was not a new use for an old product, but a new product.
Variables shaping participatory constitution-making: Insights from the experiences of small states
Authors: De Visser Maartje , Perham Elisabeth
Published: November 2022

One of the assumptions that undergirds, sometimes implicitly, much of the contemporary push for participatory constitution-making is that meaningful popular involvement is easier to achieve in units with fewer inhabitants. This article critically interrogates that view, using the experience of small states (understood as those with no more than 1.5 million inhabitants) during constitution-making processes. It suggests that population size is not always a decisive or even significant variable when it comes to the type and quality of popular input realized during constitution-making in small states. Instead, five other macrocultural and environmental variables that, either alone or together, may have a greater impact are identified: democratic history and elite stewardship; the enduring presence of traditional orderings of society and approaches to governance; the ethnic and religious make-up of society; the available human capital and state of economic development; and physical geography. Drawing on case studies from the Asia-Pacific region, we show how these variables play out and highlight the need for contextual assessments of participatory constitution-making, also within the small state universe, to avoid falling into the “usual suspect” trap that has long plagued work in comparative constitutional law generally. This article further suggests that the relevance of the five variables mentioned does not appear to be peculiar to small states, which means that these variables can similarly be profitably used in studies of participatory processes generally.
A Nomenclatural System for Outbred Animals,,
Authors:   Institute of Laboratory Animal Resources, Committee on Nomenclature
Published: November 2022

EDITOR’S NOTE

With the possible exception of inbred mice, the identification of laboratory animals has been in a state of anarchy until very recently. In a letter to the editor of LABORATORY ANIMAL CARE (19: 121–123, 1969), Mr. Samuel Poiley outlined the general principles of a system of nomenclature being developed by the Committee on Nomenclature of the ILAR. This journal requires that authors use standard terminology for rats and mice as listed in the ILAR publication ANIMALS FOR RESEARCH. We welcome the following report which represents a system of nomenclature for outbred animals and publish it as a service to the scientific community. Authors of papers submitted to this journal will be expected to identify their animals by this system. We urge the editors of other scientific publications to consider the merits of adopting standard terminology to end the reign of confusion in animal identification.
Which mediated social interactions satisfy the need to belong?
Authors: Hall Jeffrey A , Pennington Natalie , Merolla Andy J
Published: November 2022

This investigation uses the two-process model of needs to explore differences between face-to-face communication and interpersonal media in terms of belongingness need satisfaction. Using experience sampling methods, Study 1 (N = 117) explored change in feelings of loneliness and connection from interpersonal media use within a day. Study 2 (N = 1,747) examined the association between loneliness and life satisfaction as mediated by patterns of interpersonal media use in the year following the COVID-19 outbreak. Study 3 (N = 303) experimentally manipulated social belonging to examine changes in interpersonal media use and resulting feelings of connection and disconnection. Overall, when individuals were more connected, their behaviors were more consistent with the two-process model, compared to when they felt disconnected. Additionally, although some interpersonal media use was better than no social contact at all, interpersonal media are not equally capable of satisfying belongingness needs.
Premature aging as an accumulation of deficits in young adult survivors of pediatric cancer
Authors: Williams AnnaLynn M , Mandelblatt Jeanne , Wang Mingjuan , Armstrong Gregory T , Bhakta Nickhill , Brinkman Tara M , Chemaitilly Wassim , Ehrhardt Matthew J , Mulrooney Daniel A , Small Brent J , Wang Zhaoming , Srivastava Deokumar , Robison Leslie L , Hudson Melissa M , Ness Kirsten K , Krull Kevin R
Published: November 2022

Background

We aimed to characterize premature aging as an accumulation of deficits in survivors of pediatric cancer compared with community controls and examine associations with host and treatment factors, neurocognition, and mortality.

Methods

Pediatric cancer survivors (n = 4000, median age = 28.6, interquartile range [IQR] = 23-35 years; 20 years postdiagnosis: IQR = 15-27), and community participants without a history of cancer serving as controls (n = 638, median age = 32, IQR = 25-40 years) completed clinical assessments and questionnaires and were followed for mortality through April 30, 2020 (mean [SD] follow-up = 7.0 [3.4] years). A deficit accumulation index (DAI) score was calculated from 44 aging-related items including self-reported daily function, psychosocial symptoms, and health conditions. Items were weighted from 0 (absent) to 1 (present and/or most severe), summed and divided by the total yielding a ratio (higher = more deficits). Scores less than 0.20 are robust, and 0.06 is a clinically meaningful difference. Linear regression compared the DAI in survivors and controls with an age*survivor or control interaction. Logistic regression and Cox-proportional hazards estimated the risk of neurocognitive impairment and death. Models were minimally adjusted for age, sex, and race and ethnicity.

Results

The adjusted mean DAI among survivors at age 30 years was 0.16 corresponding to age 63 years in controls (33 years premature aging; β = 0.07, 95% confidence interval [CI] = 0.06 to 0.08; P < .001). Cranial and abdominal radiation, alkylators, platinum, and neurosurgery were associated with worse DAI (P ≤ .001). Higher scores were associated with increased risk of neurocognitive impairment in all domains (P < .001) and increased risk of death (DAI = 0.20-0.35, hazard ratio = 2.80, 95% CI = 1.97 to 3.98; DAI ≥ 0.35, hazard ratio = 5.08, 95% CI = 3.52 to 7.34).

Conclusion

Pediatric cancer survivors experience clinically significant premature aging. The DAI may be used to identify survivors at greatest risk of poor health outcomes.
Vampire tourism and vampirism: the darker side of travel medicine
Authors: Rainford Aoibheann C , Flaherty Gerard T , Hallahan Brian
Published: November 2022

‘Dark tourism’ refers to travel by individuals to destinations and sites linked to death, tragedy and the macabre; with vampire tourism increasingly popular over the last 20 years. The capacity of travellers, especially those with mental disorder, to cope psychologically with travel to associated emotionally challenging destinations requires further investigation.
Sampling risk evaluations in tax audits: Some modelling issues
Authors: Lillestøl Jostein
Published: November 2022

The context of this article is the use of sample data to support claims of tax evasion at eateries, where the possibilities are overreporting of take-away sales and underreporting of cash payments. Ratios of sales amounts of alternative types are computed from the sample and used as estimates of the true yearly ratios. Decisions are made by comparison with the reported ratios in the taxpayer’s yearly income statement, allowing for sampling risk. To this end, a ‘risk distribution’ is established and its quantiles used as decision limits. There are different ways of doing the calculation and to establish the accompanying risk distribution, among them models based on Gamma-assumptions, as detailed in Lillestøl (2019, Sample Statistics as Convincing Evidence: A Tax Fraud Case. Law, Probability and Risk, 10, 149–176). They may lead to different results, more or less favourable to the taxpayer. The chosen method must therefore be fair and defensible. In this connection, the question of conditioning turns out to be relevant. The objective of this article is to explore these issues and provide some recommendations on the choice of method.
Inequality by design: The politics behind forced migrants’ access to healthcare
Authors: Roos Mechthild
Published: November 2022

When a system comes under strain, the persons most likely to suffer from the repercussions are those at and beyond its margins, as the age-old rule ‘Help yourself before helping others’ typically guides crisis management within the system. Similar behavioural patterns on the side of policy-makers have left a distinct mark on the healthcare rights of forced migrants in the context and aftermath of the so-called ‘migration crisis’ of 2015–2016, as this article demonstrates. Following the crisis, this group of persons, who are traditionally situated at the margins of society already, have been pushed further outside social and healthcare systems through increasingly restrictive incorporation policies across Europe. By analysing recent legislative reforms in four countries (Germany, Italy, Sweden, and the UK) which stood out in various ways during the crisis, this article sheds light on the increasing politicisation and polarisation of the intersection of incorporation and healthcare. It shows that the crisis induced similar responses of legal adaptation in countries with fundamentally different healthcare and incorporation systems, and analyses the dynamics behind such processes of change. The article thereby contributes to a better understanding of healthcare legislation as a reflection of political opposition to or acceptance (if not fuelling) of societal inequalities.
Military Medical Provider Perspectives During the New York COVID-19 Response
Authors: Tilley Laura , Schuler Keke , Cole Rebekah , Fahlsing Christopher , Rudinsky Sherri , Peters Sidney , Goolsby Craig
Published: November 2022

Introduction

The response to the coronavirus disease 2019 pandemic in New York City (NYC) included unprecedented support from the DoD—a response limited primarily to medical and public health response on domestic soil with intact infrastructure. This study seeks to identify the common perspectives, experiences, and challenges of DoD personnel participating in this historic response.

Materials and Methods

This is a phenomenological qualitative study of 16 military health care providers who deployed to NYC in March 2020. This study was approved by the Institutional Review Board at the USU (No. DBS.2020.123). All participants served on either the United States Naval Ship Comfort or at the Javits Center. We conducted semi-structured interviews exploring the participants’ experiences while deployed to NYC. These interview scripts were then independently coded by five research team members.

Results

We identified four common themes and 12 subthemes from the participants’ responses. The themes (subthemes) were lack of preparation (unfamiliar mission and inadequate resources); confusion about integration with civilian health care (widespread, dynamic situation, and NYC overwhelmed), communication challenges (overall, misunderstanding and miscommunication resulting in tension, and patient handoffs); and adaptation and success (general, military–civilian liaison service, positive experience, and military support necessity).

Conclusions

This study provides unique insight into the DoD’s initial response to the coronavirus disease 2019 pandemic in NYC. Using this experiential feedback from the DoD’s pandemic responders could aid planners in improving the rapidity, effectiveness, and safety of military and civilian health care system integrations that may arise in the future.
Hyper-Eddington black hole growth in star-forming molecular clouds and galactic nuclei: can it happen?
Authors: Shi Yanlong , Kremer Kyle , Grudić Michael Y , Gerling-Dunsmore Hannalore J , Hopkins Philip F
Published: November 2022

Formation of supermassive black holes (BHs) remains a theoretical challenge. In many models, especially beginning from stellar relic ‘seeds,’ this requires sustained super-Eddington accretion. While studies have shown BHs can violate the Eddington limit on accretion disc scales given sufficient ‘fuelling’ from larger scales, what remains unclear is whether or not BHs can actually capture sufficient gas from their surrounding interstellar medium (ISM). We explore this in a suite of multiphysics high-resolution simulations of BH growth in magnetized, star-forming dense gas complexes including dynamical stellar feedback from radiation, stellar mass-loss, and supernovae, exploring populations of seeds with masses $\sim 1\!-\!10^{4}\, \mathrm{M}_{\odot }$. In this initial study, we neglect feedback from the BHs: so this sets a strong upper limit to the accretion rates seeds can sustain. We show that stellar feedback plays a key role. Complexes with gravitational pressure/surface density below $\sim 10^{3}\, \mathrm{M}_{\odot }\, {\rm pc^{-2}}$ are disrupted with low star formation efficiencies so provide poor environments for BH growth. But in denser cloud complexes, early stellar feedback does not rapidly destroy the clouds but does generate strong shocks and dense clumps, allowing $\sim 1{{\ \rm per\ cent}}$ of randomly initialized seeds to encounter a dense clump with low relative velocity and produce runaway, hyper-Eddington accretion (growing by orders of magnitude). Remarkably, mass growth under these conditions is almost independent of initial BH mass, allowing rapid intermediate-mass black hole (IMBH) formation even for stellar-mass seeds. This defines a necessary (but perhaps not sufficient) set of criteria for runaway BH growth: we provide analytic estimates for the probability of runaway growth under different ISM conditions.
3D simulations of strongly magnetized non-rotating supernovae: explosion dynamics and remnant properties
Authors: Varma Vishnu , Müller Bernhard , Schneider Fabian R N
Published: November 2022

We investigate the impact of strong initial magnetic fields in core-collapse supernovae of non-rotating progenitors by simulating the collapse and explosion of a $16.9\, \mathrm{M}_\odot$ star for a strong- and weak-field case assuming a twisted-torus field with initial central field strengths of ${\approx }10^{12}$ and ${\approx }10^{6}\, \mathrm{G}$. The strong-field model has been set up with a view to the fossil-field scenario for magnetar formation and emulates a pre-collapse field configuration that may occur in massive stars formed by a merger. This model undergoes shock revival already $100\, \mathrm{ms}$ after bounce and reaches an explosion energy of $9.3\times 10^{50}\, \mathrm{erg}$ at $310\, \mathrm{ms}$, in contrast to a more delayed and less energetic explosion in the weak-field model. The strong magnetic fields help trigger a neutrino-driven explosion early on, which results in a rapid rise and saturation of the explosion energy. Dynamically, the strong initial field leads to a fast build-up of magnetic fields in the gain region to 40 per cent of kinetic equipartition and also creates sizable pre-shock ram pressure perturbations that are known to be conducive to asymmetric shock expansion. For the strong-field model, we find an extrapolated neutron star kick of ${\approx }350\, \mathrm{km}\, \mathrm{s}^{-1}$, a spin period of ${\approx }70\, \mathrm{ms}$, and no spin-kick alignment. The dipole field strength of the proto-neutron star is $2\times 10^{14}\, \mathrm{G}$ by the end of the simulation with a declining trend. Surprisingly, the surface dipole field in the weak-field model is stronger, which argues against a straightforward connection between pre-collapse fields and the birth magnetic fields of neutron stars.
Non-thermal emission from mildly relativistic dynamical ejecta of neutron star mergers
Authors: Sadeh Gilad , Guttman Or , Waxman Eli
Published: November 2022

Binary neutron star mergers are expected to produce fast dynamical ejecta, with mildly relativistic velocities extending to β = v/c > 0.6. We consider the radio to X-ray synchrotron emission produced by collisionless shocks driven by such fast ejecta into the interstellar medium. Analytical expressions are given for spherical ejecta with broken power-law mass (or energy) distributions, M(> γβ) ∝ (γβ)−s with s = sKN at γβ < γ0β0 and s = sft at γβ > γ0β0 (where γ is the Lorentz factor). For parameter values characteristic of merger calculation results – a ‘shallow’ mass distribution, 1 < sKN < 3, for the bulk of the ejecta (at γβ ≈ 0.2), and a steep, sft > 5, ‘fast tail’ mass distribution – our model provides an accurate (to tens of per cent) description of the evolution of the flux, including at the phase of deceleration to subrelativistic expansion. This is a significant improvement over earlier results, based on extrapolations of results valid for γβ ≫ 1 or ≪1 to γβ ≈ 1, which overestimate the flux by an order of magnitude for typical parameter values. It will enable a more reliable inference of ejecta parameters from future measurements of the non-thermal emission. For the merger event GW170817, the existence of a ‘fast tail’ is expected to produce detectable radio and X-ray fluxes over a time-scale of ∼104 d.
Covariance matrices for variance-suppressed simulations
Authors: Zhang Tony , Chuang Chia-Hsun , Wechsler Risa H , Alam Shadab , DeRose Joseph , Feng Yu , Kitaura Francisco-Shu , Pellejero-Ibanez Marcos , Rodríguez-Torres Sergio , To Chun-Hao , Yepes Gustavo , Zhao Cheng
Published: November 2022

Cosmological N-body simulations provide numerical predictions of the structure of the Universe against which to compare data from ongoing and future surveys, but the growing volume of the Universe mapped by surveys requires correspondingly lower statistical uncertainties in simulations, usually achieved by increasing simulation sizes at the expense of computational power. It was recently proposed to reduce simulation variance without incurring additional computational costs by adopting fixed-amplitude initial conditions. This method has been demonstrated not to introduce bias in various statistics, including the two-point statistics of galaxy samples typically used for extracting cosmological parameters from galaxy redshift survey data, but requires us to revisit current methods for estimating covariance matrices of clustering statistics for simulations. In this work, we find that it is not trivial to construct covariance matrices analytically for fixed-amplitude simulations, but we demonstrate that ezmock (Effective Zel’dovich approximation mock catalogue), the most efficient method for constructing mock catalogues with accurate two- and three-point statistics, provides reasonable covariance matrix estimates for such simulations. We further examine how the variance suppression obtained by amplitude-fixing depends on three-point clustering, small-scale clustering, and galaxy bias, and propose intuitive explanations for the effects we observe based on the ezmock bias model.
Models for metal-poor stars with different initial abundances of C, N, O, Mg, and Si − III. Grids of isochrones for −2.5 ≤ [Fe/H] ≤ −0.5 and helium abundances Y = 0.25 and 0.29 at each metallicity
Authors: VandenBerg Don A
Published: November 2022

Stellar evolutionary tracks for $0.12 \le {\cal M}/{\cal M_{\odot }}\le 1.0$ have been computed for each of several variations in the abundances of C, N, and O, assuming mass-fraction helium abundances Y = 0.25 and 0.29, and 11 metallicities in the range −2.5 ≤ [Fe/H] ≤ −0.5, in 0.2-dex increments. Such computations are provided for mixtures with [O/Fe] between +0.4 and +0.8, for different C:N:O ratios at a fixed value of [CNO/Fe] and for enhanced C. Computer codes are provided to interpolate within these grids to produce isochrones for ages ${\gtrsim}7$ Gyr and to generate magnitudes and colours for many broad-band filters using bolometric corrections based on MARCS model atmospheres and synthetic spectra. The models are compared with (i) similar computations produced by other workers, (ii) observed UV, optical, and IR colour-magnitude diagrams (CMDs), (iii) the effective temperatures, (V − IC)0 and (V − KS)0 colours of Pop. II stars in the solar neighbourhood, and (iv) empirical data for the absolute magnitude of the tip of the red-giant branch (TRGB). The isochrones are especially successful in reproducing the observed morphologies of optical CMDs and in satisfying the TRGB constraints. They also fare quite well in explaining the IR colours of low-mass stars in globular clusters, indicating that they have [O/Fe] ≈ +0.6, though some challenges remain.
The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest
Authors: Szklarczyk Damian , Kirsch Rebecca , Koutrouli Mikaela , Nastou Katerina , Mehryary Farrokh , Hachilif Radja , Gable Annika L , Fang Tao , Doncheva Nadezhda T , Pyysalo Sampo , Bork Peer , Jensen Lars J , von Mering Christian
Published: November 2022

Much of the complexity within cells arises from functional and regulatory interactions among proteins. The core of these interactions is increasingly known, but novel interactions continue to be discovered, and the information remains scattered across different database resources, experimental modalities and levels of mechanistic detail. The STRING database (https://string-db.org/) systematically collects and integrates protein–protein interactions—both physical interactions as well as functional associations. The data originate from a number of sources: automated text mining of the scientific literature, computational interaction predictions from co-expression, conserved genomic context, databases of interaction experiments and known complexes/pathways from curated sources. All of these interactions are critically assessed, scored, and subsequently automatically transferred to less well-studied organisms using hierarchical orthology information. The data can be accessed via the website, but also programmatically and via bulk downloads. The most recent developments in STRING (version 12.0) are: (i) it is now possible to create, browse and analyze a full interaction network for any novel genome of interest, by submitting its complement of encoded proteins, (ii) the co-expression channel now uses variational auto-encoders to predict interactions, and it covers two new sources, single-cell RNA-seq and experimental proteomics data and (iii) the confidence in each experimentally derived interaction is now estimated based on the detection method used, and communicated to the user in the web-interface. Furthermore, STRING continues to enhance its facilities for functional enrichment analysis, which are now fully available also for user-submitted genomes.
Structure of Escherichia coli heat shock protein Hsp15 in complex with the ribosomal 50S subunit bearing peptidyl-tRNA
Authors: Safdari Haaris A , Kasvandik Sergo , Polte Christine , Ignatova Zoya , Tenson Tanel , Wilson Daniel N
Published: November 2022

In Escherichia coli, the heat shock protein 15 (Hsp15) is part of the cellular response to elevated temperature. Hsp15 interacts with peptidyl-tRNA-50S complexes that arise upon dissociation of translating 70S ribosomes, and is proposed to facilitate their rescue and recycling. A previous structure of E. coli Hsp15 in complex with peptidyl-tRNA-50S complex reported a binding site located at the central protuberance of the 50S subunit. By contrast, recent structures of RqcP, the Hsp15 homolog in Bacillus subtilis, in complex with peptidyl-tRNA-50S complexes have revealed a distinct site positioned between the anticodon-stem-loop (ASL) of the P-site tRNA and H69 of the 23S rRNA. Here we demonstrate that exposure of E. coli cells to heat shock leads to a decrease in 70S ribosomes and accumulation of 50S subunits, thus identifying a natural substrate for Hsp15 binding. Additionally, we have determined a cryo-EM reconstruction of the Hsp15-50S-peptidyl-tRNA complex isolated from heat shocked E. coli cells, revealing that Hsp15 binds to the 50S-peptidyl-tRNA complex analogously to its B. subtilis homolog RqcP. Collectively, our findings support a model where Hsp15 stabilizes the peptidyl-tRNA in the P-site and thereby promotes access to the A-site for putative rescue factors to release the aberrant nascent polypeptide chain.
Growth dynamics of incidental meningiomas: A prospective long-term follow-up study
Authors: Strømsnes Torbjørn Austveg , Lund-Johansen Morten , Skeie Geir Olve , Eide Geir Egil , Behbahani Maziar , Skeie Bente Sandvei
Published: November 2022

Background

There is no consensus on the management of incidental meningiomas. The literature on long-term growth dynamics is sparse and the natural history of these tumors remains to be illuminated.

Methods

We prospectively assessed long-term tumor growth dynamics and survival rates during active monitoring of 62 patients (45 female, mean age 63.9 years) harboring 68 tumors. Clinical and radiological data were obtained every 6 months for 2 years, annually until 5 years, then every second year.

Results

The natural progression of incidental meningiomas during 12 years of monitoring was growth (P < .001). However, mean growth decelerated at 1.5 years and became insignificant after 8 years. Self-limiting growth patterns were seen in 43 (63.2%) tumors, non-decelerating in 20 (29.4%) and 5 (7.4%) were inconclusive due to  ≤ 2 measurements. Decelerating growth persisted once established. Within 5 years, 38 (97.4%) of 39 interventions were initiated. None developed symptoms prior to intervention. Large tumors (P < .001) involving venous sinuses (P = .039) grew most aggressively. Since inclusion 19 (30.6%) patients have died of unrelated causes and 2 (3%) from grade 2 meningiomas.

Conclusion

Active monitoring seems a safe and appropriate first-line management of incidental meningiomas. Intervention was avoided in  > 40% with indolent tumors in this cohort. Treatment was not compromised by tumor growth. Clinical follow-up seems sufficient beyond 5 years if self-limiting growth is established. Steady or accelerating growth warrant monitoring until they reach a stable state or intervention is initiated.
The microvariability and wavelength dependence of polarization degree/angle of BL Lacertae in the outburst 2020 to 2021
Authors: Imazawa Ryo , Sasada Mahito , Hazama Natsuko , Fukazawa Yasushi , Kawabata Koji S , Nakaoka Tatsuya , Akitaya Hiroshi , Bohn Thomas , Gangopadhyay Anjasha
Published: November 2022

We have obtained simultaneous and continuous photo-polarization observations of the blazar BL Lacertae in optical and near-infrared (NIR) bands during an historical outburst from 2020 to 2021. In total, 14 nights of observations were performed where 10 observations show microvariability on timescales of a few minutes to several hours. This suggests a compact emission region, and the timescales are difficult to explain by a one-zone shock-in-jet model. Moreover, we found significant differences in the polarization degree (PD) and angle between optical and NIR bands. Nine nights showed a PD in the optical band that is greater than or equal to that in the NIR band, which can be explained by either a shock-in-jet model or the Turbulent Extreme Multi-Zone (TEMZ) model. On the other hand, five nights showed higher PD in an NIR band than an optical band, which cannot be explained by simple shock-in-jet models nor the simple TEMZ model. The observed timescales and wavelength-dependency of the PD and polarization angle suggest the existence of complicated multiple emission regions such as an irregular TEMZ model.
X-ray spectroscopy of the accretion disk corona source 2S 0921−630 with Suzaku archival data
Authors: Yoneyama Tomokage , Dotani Tadayasu
Published: November 2022

2S 0921−630 is an eclipsing low-mass X-ray binary (LMXB) with an orbital period of ∼9 d. Past X-ray observations have revealed that 2S 0921−630 has an extended accretion disk corona (ADC), from which most of the X-rays from the system are emitted. We report the result of our Suzaku archival data analysis of 2S 0921−630. The average X-ray spectrum is reproduced with a blackbody emission (kTbb ∼ 0.3 keV) Comptonized by optically thick gas (“Compton cloud”; optical depth τ ∼ 21) with a temperature of ∼2 keV, combined with 13 emission lines. We find that most of the emission lines correspond to highly ionized atoms: O, Ne, Mg, Si, S, Ar, and Fe. A Kα emission line and an absorption edge of semi-neutral iron (Fe  textsci– textscxvii) are also detected. The semi-neutral iron Kα line is significantly broad, with a width of 0.11 ± 0.02 keV in sigma, which corresponds to the Doppler broadening by the Kepler motion at a radius of ∼109 cm. We suggest that the observed semi-neutral iron line originates at the inner part of the accretion disk in the immediate outside of the Compton cloud, i.e., the Compton cloud may have a radius of ∼109 cm.
Medical cannabis in schools: A qualitative study on the experiences of clinicians
Authors: Mansell Holly , Zaslawski Zina , Kelly Lauren E , Lougheed Taylor , Brace Tracy , Alcorn Jane
Published: November 2022

Objectives

Guidance is lacking for medical cannabis use in Canadian schools in both legislation and approach; the impact of ambiguous policy on patient care is unknown. A qualitative study was undertaken to explore the experiences of clinicians who care for school-aged children who take medical cannabis.

Methods

Semi-structured interviews were recorded and transcribed verbatim. Qualitative content analysis performed using the Dedoose qualitative software ascribed meaning units and codes, which were further consolidated into categories and subcategories.

Results

Thirteen physicians were interviewed virtually, representing seven provinces in Canada. The physicians provided care for between five and hundreds of school-aged children who took medical cannabis. The most common indications were refractory seizure disorders and autism. The interviews provided rich descriptions on perceptions of medical cannabis in schools, and in general. Five overarching categories were identified across both domains including variability, challenges (subcategories: lack of knowledge, stigma, lack of policy, and pragmatic challenges), potential solutions (subcategories: treat it like other medications, communication, education, and family support), positive experiences and improvements over time.

Conclusion

In Canada, cannabis-based medicine use in schools still faces important challenges. Effective education, communication, family support and policy refinements that allow cannabis to be treated like other prescription medications are recommended to improve the status quo. These findings will guide the C4T Medical Cannabis in Schools Working Group’s future priorities and initiatives.
Breeding crops for drought-affected environments and improved climate resilience
Authors: Cooper Mark , Messina Carlos D
Published: November 2022

Breeding climate-resilient crops with improved levels of abiotic and biotic stress resistance as a response to climate change presents both opportunities and challenges. Applying the framework of the “breeder’s equation,” which is used to predict the response to selection for a breeding program cycle, we review methodologies and strategies that have been used to successfully breed crops with improved levels of drought resistance, where the target population of environments (TPEs) is a spatially and temporally heterogeneous mixture of drought-affected and favorable (water-sufficient) environments. Long-term improvement of temperate maize for the US corn belt is used as a case study and compared with progress for other crops and geographies. Integration of trait information across scales, from genomes to ecosystems, is needed to accurately predict yield outcomes for genotypes within the current and future TPEs. This will require transdisciplinary teams to explore, identify, and exploit novel opportunities to accelerate breeding program outcomes; both improved germplasm resources and improved products (cultivars, hybrids, clones, and populations) that outperform and replace the products in use by farmers, in combination with modified agronomic management strategies suited to their local environments.
Scaffold-based tissue engineering strategies for soft–hard interface regeneration
Authors: Li Yibo , Zhou Mo , Zheng Wenzhuo , Yang Jianying , Jiang Nan
Published: November 2022

Repairing injured tendon or ligament attachments to bones (enthesis) remains costly and challenging. Despite superb surgical management, the disorganized enthesis newly formed after surgery accounts for high recurrence rates after operations. Tissue engineering offers efficient alternatives to promote healing and regeneration of the specialized enthesis tissue. Load-transmitting functions thus can be restored with appropriate biomaterials and engineering strategies. Interestingly, recent studies have focused more on microstructure especially the arrangement of fibers since Rossetti successfully demonstrated the variability of fiber underspecific external force. In this review, we provide an important update on the current strategies for scaffold-based tissue engineering of enthesis when natural structure and properties are equally emphasized. We firstly described compositions, structures and features of natural enthesis with their special mechanical properties highlighted. Stimuli for growth, development and healing of enthesis widely used in popular strategies are systematically summarized. We discuss the fabrication of engineering scaffolds from the aspects of biomaterials, techniques and design strategies and comprehensively evaluate the advantages and disadvantages of each strategy. At last, this review pinpoints the remaining challenges and research directions to make breakthroughs in further studies.