bluuebunny/crossref_metadata_2025 huggingface dataset:
3D craniofacial reconstruction framework using elastic surface deformation based on automatic landmark positioning
Authors: Suputra Putu Hendra , Sensusiati Anggraini Dwi , Artaria Myrtati Dyah , Yuniarno Eko Mulyanto , Purnama I Ketut Eddy
Published: May 2023

Computer‐aided craniofacial reconstruction (CFR) is a process that aims to estimate facial impressions based on skull remains. It mimics the conventional method with a conceptual model‐based framework. The existing problems in CFR are that landmark annotation is expert‐dependent, landmark processing in the 3D domain has volumetric challenges, and a method based on a population's morphological characteristics (templates). A framework with three stages is proposed: Building a craniofacial model, automatic landmark detection, and surface deformation. Machine learning is deployed to draw local surface correlations as landmarks and automatically detects their position. The local surface context is extracted using the Surface Curvature Feature (SCF) as a 3D descriptor. Using a cluster‐based filter, the average distance (to the ground truth) of the top 20 points is 0.0326 units. Cluster‐based filters are better than mass‐radius‐based filters and consistently give better pinpoint accuracy, especially in multi‐cluster cases. Training data consists of 140,000 SCF for ten landmark classes. The third stage, surface deformation, fits the facial template to the cranial based on the corresponding facial‐cranial landmarks. Five experts from the Anthropology department stated that of the reconstruction results, 91.5% could retain the template details and are accepted as the natural shape of the human face.
Decoding the Guidelines of Invasive Pulmonary Aspergillosis in Critical Care Setting: Imaging Perspective
Authors: Garg Anisha , Bhalla Ashu Seith , Naranje Priyanka , Vyas Surabhi , Garg Mandeep
Published: May 2023

Invasive pulmonary aspergillosis (IPA) is a common, life-threatening opportunistic fungal infection seen in susceptible individuals especially those admitted in critical care units. Multiple guidelines have been promulgated for the diagnosis of IPA, some of which are all inclusive, while others cater to specific patient groups. Microbiology forms the crux of the majority of the diagnostic tests/criteria; however, results take a considerable amount of time. Radiology can play an important role by bridging the gap to reach at an early diagnosis. Thus, the role of a radiologist cannot be overemphasized to recognize the typical and atypical imaging manifestations of invasive aspergillosis and aid in the swift management of these cases. This review decodes the terminology and various diagnostic criteria for IPA relevant to imaging studies. Further, the differences in imaging manifestations of IPA in neutropenic and non-neutropenic patients are also discussed.
“Where there’s a will, there’s a way:” contingency, mobility, and subjectification at the Stratemeyer Syndicate
Authors: Klepper Martin
Published: May 2023

This essay connects the mass-produced books of the Stratemeyer Syndicate, The Nancy Drew Mystery Stories since 1930 and the Hardy Boys Adventures since 1927, with the discourses of self-help and self-improvement and argues that the effects these books have on their young readers instigate the formation of a very specific (white, middle class) subjectivity. This modern mode of relating to oneself includes an adjustable, self-assertive, self-monitoring personality, which can be understood as an answer to the challenges of the Second Industrialization and the contingencies connected to the acceleration, fragmentation, de-familiarizations, and individualization of modernity. At the same time, the essay argues, the novels also include a very specific position in terms of gender, race, and class, which, in spite of the figure of Nancy Drew, remains fundamentally linked to the values of patriarchy, the middle class and whiteness.
The use of intellectual property right bundles and firm performance in China
Authors: Zhang Li , Shan Xiaoguang
Published: May 2023

Intellectual property rights (IPRs) have become increasingly important for firms in today’s knowledge-based economy, as evidenced by the strong growth in their use. The vital role of IPRs has motivated research into their association with firm performance. However, few firm-level studies have been conducted in developing countries. Moreover, empirical studies on the use of IPR bundles and their economic performance are scarce. To fill this gap, this study first illuminates how the joint use of different IPRs varies with firm characteristics, second, it analyses the association of such joint use with firm performance, based on a constructed large dataset that merges firm-level information from China’s Annual Survey of Industrial Enterprises with data on IPR filings from the China National Intellectual Property Administration. Results indicate that the joint use of different IPRs is strongly correlated with the industrial sector and firm size. Firms that use IPR bundles also have much greater economic performance than those that rely only on single types, indicating the existing complementarity between these rights. This study advances the understanding of the relationship between IPRs and firm performance and emphasises the complementary effect between different types of IPRs, demonstrating the significance of utilising various intellectual property mechanisms fully to increase firms’ competitive advantages.
Disequilibrium and complexity across scales: a patch-dynamics framework for organizational ecology
Authors: Xu Jin , Cornelissen Joep
Published: May 2023

Based on equilibrium assumptions, traditional ecological models have been widely applied in the fields of management and organization studies. While research using these models is still ongoing, studies have nonetheless struggled with ways to address multiple levels of analysis, uncertainty, and complexity in their analyses. This paper conceptualizes the dynamic co-evolution mechanisms that operate in an ecosystem across multiple organizational scales. Specifically, informed by recent advances in modelling in biology, a general ‘patch-dynamics’ framework that is theoretically and methodologically able to capture disequilibrium, uncertainty, disturbances, and changes in organizational populations or ecosystems, as complex and dynamically evolving resource environments are introduced. Simulation models are built to show the patch-dynamics framework’s functioning and test its robustness. The patch-dynamics framework and modelling methodology integrates equilibrium and disequilibrium perspectives, co-evolutions across multiple organization levels, uncertainties, and random disturbances into a single framework, opening new avenues for future research on topics in the field of management and organization studies, as well as on the mechanisms that shape ecosystems. Such a framework has the potential to help analyse the sustainability and healthiness of the business environment, and deserves more attention in future research on management and organization theory, particularly in the context of significant uncertainty and disturbances in business and management practice. Overall, the paper offers a distinct theoretical perspective and methodology for modelling population and ecosystem dynamics across different scales.
Classical Nambu brackets in higher dimensions
Authors: Chandre Cristel , Horikoshi Atsushi
Published: May 2023

We consider n-linear Nambu brackets in dimension N higher than n. Starting from a Hamiltonian system with a Poisson bracket and K Casimir invariants defined in the phase space of dimension N = K + 2M, where M is the number of effective degrees of freedom, we investigate a necessary and sufficient condition for this system to possess n-linear Nambu brackets. For the case of n = 3, by looking for the possible solutions to the fundamental identity, the condition is found to be N = K + 2, i.e., the system should have effectively one degree of freedom. Locally, it is shown that there is only one fundamental solution, up to a local change of variables, and this solution is the canonical Nambu bracket, generated by Levi–Cività tensors. These results generalize to the case of n(≥4)-linear Nambu brackets.
Wideband RCS reduction based on a simple chessboard metasurface
Authors: Zhou C. F. , Yu Q. F. , Gustafson C. , Lau B. K.
Published: May 2023

To avoid being detected by radar, it is necessary to reduce stealthy military platforms' radar cross section (RCS). The operation of overlaying the metasurface (MS) on the targets is a good solution. A simple chessboard MS structure that can achieve low RCS over a large bandwidth is proposed. Only one unit cell is used to construct the MS. First, the unit cell working in 0.5 and 1−λ modes is designed to achieve a stable phase difference of 180° for y- and x-polarized waves. Then, the unit cells and rotated ones are used to form a chessboard structure with different distributions. The compared results show that the chessboard MS with 2 × 2 quadrants can facilitate the widest 10 dB RCS reduction band of 111% and the largest RCS reduction. The proposed structure exhibits excellent RCS reduction even when irradiated by y- and x-polarized waves at an oblique incidence of 30°.
Electron trajectories in a collisional crossed-field gap
Authors: Garner Allen L. , Komrska Allison M. , Breen Lorin I. , Loveless Amanda M. , Cartwright Keith L.
Published: May 2023

The Hull cutoff represents the maximum magnetic field in a vacuum crossed-field gap (CFG) such that an electron emitted from the cathode reaches the anode. Prior studies demonstrated that introducing ions into a CFG always causes increased excursion of electrons toward the anode. In this paper, we assess a collisional CFG by incorporating collision frequency into the electron force law. The theoretical electron trajectories agree well with a one-dimensional particle-in-cell simulation and demonstrate that emitted electrons always cross a collisional CFG. We derive a modified Hull cutoff condition for a collisional CFG corresponding to an electron reaching the anode with zero velocity in the direction of the electric field. Rather than representing the threshold for magnetic insulation, this condition gives the maximum magnetic field and maximum collision frequency for which an electron reaches the anode without turning around; higher magnetic fields and/or collision frequencies cause the electron to turn around before crossing the gap. Further increasing either quantity causes the electron to change direction more frequently as it crosses the gap, noticeably increasing the transit time with each change in electron direction. In the limit of high collision frequency, the electron velocity across the gap approaches a constant, meaning that electrons will reach the anode at nonzero velocity. The transit time above this condition increases smoothly and monotonically with increasing magnetic field or collision frequency. These results elucidate the implications of collisions on magnetic insulation for future assessments of the limiting current in a collisional CFG.
Spatially explicit effective reproduction numbers from incidence and mobility data
Authors: Trevisin Cristiano , Bertuzzo Enrico , Pasetto Damiano , Mari Lorenzo , Miccoli Stefano , Casagrandi Renato , Gatto Marino , Rinaldo Andrea
Published: May 2023

Current methods for near real-time estimation of effective reproduction numbers from surveillance data overlook mobility fluxes of infectors and susceptible individuals within a spatially connected network (the metapopulation). Exchanges of infections among different communities may thus be misrepresented unless explicitly measured and accounted for in the renewal equations. Here, we first derive the equations that include spatially explicit effective reproduction numbers, ℛ

k

(
t
), in an arbitrary community
k
. These equations embed a suitable connection matrix blending mobility among connected communities and mobility-related containment measures. Then, we propose a tool to estimate, in a Bayesian framework involving particle filtering, the values of ℛ

k

(
t
) maximizing a suitable likelihood function reproducing observed patterns of infections in space and time. We validate our tools against synthetic data and apply them to real COVID-19 epidemiological records in a severely affected and carefully monitored Italian region. Differences arising between connected and disconnected reproduction numbers (the latter being calculated with existing methods, to which our formulation reduces by setting mobility to zero) suggest that current standards may be improved in their estimation of disease transmission over time.
The build-up of the present-day tropical diversity of tetrapods
Authors: Quintero Ignacio , Landis Michael J. , Jetz Walter , Morlon Hélène
Published: May 2023

The extraordinary number of species in the tropics when compared to the extra-tropics is probably the most prominent and consistent pattern in biogeography, suggesting that overarching processes regulate this diversity gradient. A major challenge to characterizing which processes are at play relies on quantifying how the frequency and determinants of tropical and extra-tropical speciation, extinction, and dispersal events shaped evolutionary radiations. We address this question by developing and applying spatiotemporal phylogenetic and paleontological models of diversification for tetrapod species incorporating paleoenvironmental variation. Our phylogenetic model results show that area, energy, or species richness did not uniformly affect speciation rates across tetrapods and dispute expectations of a latitudinal gradient in speciation rates. Instead, both neontological and fossil evidence coincide in underscoring the role of extra-tropical extinctions and the outflow of tropical species in shaping biodiversity. These diversification dynamics accurately predict present-day levels of species richness across latitudes and uncover temporal idiosyncrasies but spatial generality across the major tetrapod radiations.
In-plane spin excitation of skyrmion bags
Authors: Li 李 Shuang 爽 , Li 李 Ke-Xin 可欣 , Liu 刘 Zhao-Hua 照华 , Zhu 朱 Qi-Yuan 起源 , Zhao 赵 Chen-Bo 晨博 , Zhang 张 Hu 虎 , Shi 石 Xing-Qiang 兴强 , Wang 王 Jiang-Long 江龙 , Wang 王 Rui-Ning 瑞宁 , Lian 连 Ru-Qian 如乾 , Gong 巩 Peng-Lai 朋来 , Jin 金 Chen-Dong 晨东
Published: May 2023

Skyrmion bags are spin structures with arbitrary topological charges, each of which is composed of a big skyrmion and several small skyrmions. In this work, by using an in-plane alternating current (AC) magnetic field, we investigate the spin-wave modes of skyrmion bags, which behave differently from the clockwise (CW) rotation mode and the counterclockwise (CCW) rotation mode of skyrmions because of their complex spin topological structures. The in-plane excitation power spectral density shows that each skyrmion bag possesses four resonance frequencies. By further studying the spin dynamics of a skyrmion bag at each resonance frequency, the four spin-wave modes, i.e., a CCW-CW mode, two CW-breathing modes with different resonance strengths, and an inner CCW mode, appear as a composition mode of outer skyrmion–inner skyrmions. Our results are helpful in understanding the in-plane spin excitation of skyrmion bags, which may contribute to the characterization and detection of skyrmion bags, as well as the applications in logic devices.
Maximized internal scattering in heterostack Ti3C2T
x
MXene/graphene oxide film for effective electromagnetic interference shielding
Authors: Lee Gang San , Yoon Yeo Hoon , Iqbal Aamir , Kwon Jisung , Yun Taeyeong , Sasikala Suchithra Padmajan , Hassan Tufail , Kim Jin Goo , Kim Jun Tae , Lee Chan Woo , Kim Myung-Ki , Koo Chong Min , Kim Sang Ouk
Published: May 2023

Two-dimensional (2D) MXenes have attracted significant attention in electromagnetic interference (EMI) shielding applications due to their excellent metallic conductivity, high surface area, 2D geometry, tunable surface chemistry, and solution processability. In this study, we present a straightforward way of introducing multiple nanoscale interfaces into Ti3C2T
x
MXenes using insulating graphene oxide (GO) intercalants to enhance internal scattering, resulting in improved EMI shielding effectiveness (SE). The amine-functionalized MXene with positive surface charge and negatively charged GO flakes are electrostatically self-assembled to form a 2D/2D heterostack of MXene/GO nanosheets. The resultant 2D/2D alternating heterostack of MXene/GO bearing multiple internal interfaces with significant impedance mismatch enhances the internal scattering of incident electromagnetic (EM) waves. Interestingly, despite their inferior electrical conductivity, the MXene/GO heterostack films exhibit higher EMI SE values than the randomly mixed hybrid films, and even outperform pristine MXene films. These MXene/GO heterostack films with enhanced absorption of EM waves via the strong internal scattering effect suggest a valuable pathway toward practical EMI shielding with thin and lightweight features.
Relative Age Within School Grade, Including Delayed and Accelerated School Start: Associations With Midlife Psychiatric Disorders, Suicide, and Alcohol- and Drug-Related Mortality
Authors: Keyes Katherine M , Kristensen Petter , Undem Karina , Mehlum Ingrid Sivesind
Published: May 2023

Within a school grade, children who are young for grade are at increased risk of psychiatric diagnoses, but the long-term implications remain understudied, and associations with students who delay or accelerate entry underexplored. We used Norwegian birth cohort records (birth years: 1967–1976, n = 626,928) linked to records in midlife. On-time school entry was socially patterned; among those born in December, 23.0% of children in the lowest socioeconomic position (SEP) delayed school entry, compared with 12.2% among the highest SEP. Among those who started school on time, there was no evidence for long-term associations between birth month and psychiatric/behavioral disorders or mortality. Controlling for SEP and other confounders, delayed school entry was associated with increased risk of psychiatric disorders and mortality. Children with delayed school entry were 1.31 times more likely to die by suicide (95% confidence interval: 1.07, 1.61) by midlife, and 1.96 times more likely to die from drug-related death (95% confidence interval: 1.59, 2.40) by midlife than those born late in the year who started school on time. Associations with delayed school entry are likely due to selection, and results thus underscore that long-term health risks can be tracked early in life, including through school entry timing, and are highly socially patterned.
Cytomegalovirus and Cardiovascular Disease: A Hypothetical Role for Viral G-Protein-Coupled Receptors in Hypertension
Authors: Bomfim Gisele F , Priviero Fernanda , Poole Emma , Tostes Rita C , Sinclair John H , Stamou Dimitrios , Uline Mark J , Wills Mark R , Webb R Clinton
Published: May 2023

Cytomegalovirus (CMV) is a member of the β-herpesviruses and is ubiquitous, infecting 50%–99% of the human population depending on ethnic and socioeconomic conditions. CMV establishes lifelong, latent infections in their host. Spontaneous reactivation of CMV is usually asymptomatic, but reactivation events in immunocompromised or immunosuppressed individuals can lead to severe morbidity and mortality. Moreover, herpesvirus infections have been associated with several cardiovascular and post-transplant diseases (stroke, atherosclerosis, post-transplant vasculopathy, and hypertension). Herpesviruses, including CMV, encode viral G-protein-coupled receptors (vGPCRs) that alter the host cell by hijacking signaling pathways that play important roles in the viral life cycle and these cardiovascular diseases. In this brief review, we discuss the pharmacology and signaling properties of these vGPCRs, and their contribution to hypertension. Overall, these vGPCRs can be considered attractive targets moving forward in the development of novel hypertensive therapies.
Textural properties of microglial activation in Alzheimer’s disease as measured by (R)-[11C]PK11195 PET
Authors: Lapo Pais Marta , Jorge Lília , Martins Ricardo , Canário Nádia , Xavier Ana Carolina , Bernardes Rui , Abrunhosa Antero , Santana Isabel , Castelo-Branco Miguel
Published: May 2023

Alzheimer’s disease is the most common form of dementia worldwide, accounting for 60–70% of diagnosed cases. According to the current understanding of molecular pathogenesis, the main hallmarks of this disease are the abnormal accumulation of amyloid plaques and neurofibrillary tangles. Therefore, biomarkers reflecting these underlying biological mechanisms are recognized as valid tools for an early diagnosis of Alzheimer’s disease. Inflammatory mechanisms, such as microglial activation, are known to be involved in Alzheimer’s disease onset and progression. This activated state of the microglia is associated with increased expression of the translocator protein 18 kDa. On that account, PET tracers capable of measuring this signature, such as (R)-[11C]PK11195, might be instrumental in assessing the state and evolution of Alzheimer’s disease. This study aims to investigate the potential of Gray Level Co-occurrence Matrix-based textural parameters as an alternative to conventional quantification using kinetic models in (R)-[11C]PK11195 PET images. To achieve this goal, kinetic and textural parameters were computed on (R)-[11C]PK11195 PET images of 19 patients with an early diagnosis of Alzheimer’s disease and 21 healthy controls and submitted separately to classification using a linear support vector machine. The classifier built using the textural parameters showed no inferior performance compared to the classical kinetic approach, yielding a slightly larger classification accuracy (accuracy of 0.7000, sensitivity of 0.6957, specificity of 0.7059 and balanced accuracy of 0.6967). In conclusion, our results support the notion that textural parameters may be an alternative to conventional quantification using kinetic models in (R)-[11C]PK11195 PET images. The proposed quantification method makes it possible to use simpler scanning procedures, which increase patient comfort and convenience. We further speculate that textural parameters may also provide an alternative to kinetic analysis in (R)-[11C]PK11195 PET neuroimaging studies involving other neurodegenerative disorders. Finally, we recognize that the potential role of this tracer is not in diagnosis but rather in the assessment and progression of the diffuse and dynamic distribution of inflammatory cell density in this disorder as a promising therapeutic target.
Altered directional functional connectivity underlies post-stroke cognitive recovery
Authors: Soleimani Behrad , Dallasta Isabella , Das Proloy , Kulasingham Joshua P , Girgenti Sophia , Simon Jonathan Z , Babadi Behtash , Marsh Elisabeth B
Published: May 2023

Cortical ischaemic strokes result in cognitive deficits depending on the area of the affected brain. However, we have demonstrated that difficulties with attention and processing speed can occur even with small subcortical infarcts. Symptoms appear independent of lesion location, suggesting they arise from generalized disruption of cognitive networks. Longitudinal studies evaluating directional measures of functional connectivity in this population are lacking. We evaluated six patients with minor stroke exhibiting cognitive impairment 6–8 weeks post-infarct and four age-similar controls. Resting-state magnetoencephalography data were collected. Clinical and imaging evaluations of both groups were repeated 6- and 12 months later. Network Localized Granger Causality was used to determine differences in directional connectivity between groups and across visits, which were correlated with clinical performance. Directional connectivity patterns remained stable across visits for controls. After the stroke, inter-hemispheric connectivity between the frontoparietal cortex and the non-frontoparietal cortex significantly increased between visits 1 and 2, corresponding to uniform improvement in reaction times and cognitive scores. Initially, the majority of functional links originated from non-frontal areas contralateral to the lesion, connecting to ipsilesional brain regions. By visit 2, inter-hemispheric connections, directed from the ipsilesional to the contralesional cortex significantly increased. At visit 3, patients demonstrating continued favourable cognitive recovery showed less reliance on these inter-hemispheric connections. These changes were not observed in those without continued improvement. Our findings provide supporting evidence that the neural basis of early post-stroke cognitive dysfunction occurs at the network level, and continued recovery correlates with the evolution of inter-hemispheric connectivity.
Impact of Mandatory Infectious Disease Specialist Approval on Hospital-Onset Clostridioides difficile Infection Rates and Testing Appropriateness
Authors: Lin Michael Y , Stein Brian D , Kothadia Sonya M , Blank Samantha , Schoeny Michael E , Tomich Alexander , Hayden Mary K , Segreti John
Published: May 2023

Background

Inappropriate Clostridioides difficile testing is common in the hospital setting, leading to potential overdiagnosis of infection when single-step nucleic acid amplification testing is used. The potential role of infectious diseases (ID) specialists in enforcing appropriate C. difficile testing is unclear.

Methods

At a single 697-bed academic hospital, we performed a retrospective study from 1 March 2012 to 31 December 2019 comparing hospital-onset C. difficile infection (HO-CDI) rates during 3 consecutive time periods: baseline 1 (37 months, no decision support), baseline 2 (32 months, computer decision support), and intervention period (25 months, mandatory ID specialist approval for all C. difficile testing on hospital day 4 or later). We used a discontinuous growth model to assess the impact of the intervention on HO-CDI rates.

Results

During the study period, we evaluated C. difficile infections across 331 180 admission and 1 172 015 patient-days. During the intervention period, a median of 1 HO-CDI test approval request per day (range, 0–6 alerts/day) was observed; adherence by providers with obtaining approval was 85%. The HO-CDI rate was 10.2, 10.4, and 4.3 events per 10 000 patient-days for each consecutive time period, respectively. In adjusted analysis, the HO-CDI rate did not differ significantly between the 2 baseline periods (P = .14) but did differ between the baseline 2 period and intervention period (P < .001).

Conclusions

An ID-led C. difficile testing approval process was feasible and was associated with a >50% decrease in HO-CDI rates, due to enforcement of appropriate testing.
A Single Reference Interval for Interpreting Serum Free Light Chains across Patients with Varying Renal Function
Authors: Azimi Vahid , Slade Michael , Fiala Mark , Fortier Julie M , Stockerl-Goldstein Keith , Frater John L , Brestoff Jonathan R , Jackups Ronald , Zaydman Mark A
Published: May 2023

Background

Serum free light chain (sFLC) assays are interpreted using a sFLC-ratio-based reference interval (manufacturer’s interval) that was defined using a cohort of healthy patients. However, renal impairment elevates the sFLC-ratio, leading to a high false positive rate when using the manufacturer’s interval. Prior studies have developed renal-specific reference intervals; however, this approach has not been widely adopted due to practical limitations. Thus, there remains a critical need for a renally robust sFLC interpretation method.

Methods

Retrospective data mining was used to define patient cohorts that reflect the spectrum of renal function seen in clinical practice. Two new reference intervals, one based on the sFLC-ratio and one based on a novel principal component analysis (PCA)-based metric, were developed for the FREELITE assay (Binding Site) on the Roche Cobas c501 instrument (Roche).

Results

Compared to the manufacturer’s reference interval, both new methods exhibited significantly lower false positive rates and greater robustness to renal function while maintaining equivalent sensitivity for monoclonal gammopathy (MG) diagnosis. While not significantly different, the point estimate for sensitivity was highest for the PCA-based approach.

Conclusion

Renally robust sFLC interpretation using a single reference interval is possible given a reference cohort that reflects the variation in renal function observed in practice. Further studies are needed to achieve sufficient power and determine if the novel PCA-based metric offers superior sensitivity for MG diagnosis. These new methods offer the practical advantages of not requiring an estimated glomerular filtration rate result or multiple reference intervals, thereby lowering practical barriers to implementation.
Base-excision restriction enzymes: expanding the world of epigenetic immune systems
Authors: Kojima Kenji K , Kobayashi Ichizo
Published: May 2023

The restriction enzymes examined so far are phosphodiesterases, which cleave DNA strands by hydrolysing phosphodiester bonds. Based on the mobility of restriction-modification systems, recent studies have identified a family of restriction enzymes that excise a base in their recognition sequence to generate an abasic (AP) site unless the base is properly methylated. These restriction glycosylases also show intrinsic but uncoupled AP lyase activity at the AP site, generating an atypical strand break. Action of an AP endonuclease at the AP site may generate another atypical break, rejoining/repairing of which is difficult. This PabI family of restriction enzymes contain a novel fold (HALFPIPE) and show unusual properties, such as non-requirement of divalent cations for cleavage. These enzymes are present in Helicobacteraceae/Campylobacteraceae and in few hyperthermophilic archaeal species. In Helicobacter genomes, their recognition sites are strongly avoided, and the encoding genes are often inactivated by mutations or replacement, indicating that their expression is toxic for the cells. The discovery of restriction glycosylases generalizes the concept of restriction-modification systems to epigenetic immune systems, which may use any mode of damage to DNA that are considered ‘non-self’ based on epigenetic modifications. This concept will add to our understanding of immunity and epigenetics.
Cross-sexual Transfer Revisited
Authors: Anderson Andrew P , Falk Jay Jinsing
Published: May 2023

In her influential book “Developmental Plasticity and Evolution,” Mary Jane West-Eberhard introduced the concept of cross-sexual transfer, where traits expressed in one sex in an ancestral species become expressed in the other sex. Despite its potential ubiquity, we find that cross-sexual transfer has been under-studied and under-cited in the literature, with only a few experimental papers that have invoked the concept. Here, we aim to reintroduce cross-sexual transfer as a powerful framework for explaining sex variation and highlight its relevance in current studies on the evolution of sexual heteromorphism (different means or modes in trait values between the sexes). We discuss several exemplary studies of cross-sexual transfer that have been published in the past two decades, further building on West-Eberhard’s extensive review. We emphasize two scenarios as potential avenues of study, within-sex polymorphic and sex-role reversed species, and discuss the evolutionary and adaptive implications. Lastly, we propose future questions to expand our understanding of cross-sexual transfer, from nonhormonal mechanisms to the identification of broad taxonomic patterns. As evolutionary biologists increasingly recognize the nonbinary and often continuous nature of sexual heteromorphism, the cross-sexual framework has important utility for generating novel insights and perspectives on the evolution of sexual phenotypes across diverse taxa.
Analysis of the ratio of ℓ1 and ℓ2 norms for signal recovery with partial support information
Authors: Ge Huanmin , Chen Wengu , Ng Michael K
Published: May 2023

The ratio of $\ell _{1}$ and $\ell _{2}$ norms, denoted as $\ell _{1}/\ell _{2}$, has presented prominent performance in promoting sparsity. By adding partial support information to the standard $\ell _{1}/\ell _{2}$ minimization, in this paper, we introduce a novel model, i.e. the weighted $\ell _{1}/\ell _{2}$ minimization, to recover sparse signals from the linear measurements. The restricted isometry property based conditions for sparse signal recovery in both noiseless and noisy cases through the weighted $\ell _{1}/\ell _{2}$ minimization are established. And we show that the proposed conditions are weaker than the analogous conditions for standard $\ell _{1}/\ell _{2}$ minimization when the accuracy of the partial support information is at least $50\%$. Moreover, we develop effective algorithms and illustrate our results via extensive numerical experiments on synthetic data in both noiseless and noisy cases.
An update on studies characterizing adaptive immune responses in SARS-CoV-2 infection and COVID-19 vaccination
Authors: da Silva Antunes Ricardo , Grifoni Alba , Frazier April , Weiskopf Daniela , Sette Alessandro
Published: May 2023

In this brief opinion piece, we highlight our studies characterizing adaptive SARS-CoV-2 immune responses in infection and vaccination, and the ability of SARS-CoV-2-specific T cells to recognize emerging variants of concern, and the role of pre-existing cross-reactive T cells. In the context of the debate on correlates of protection, the pandemic’s progression in the past 3 years underlined the need to consider how different adaptive immune responses might differentially contribute to protection from SARS-CoV-2 infection versus COVID-19 disease. Lastly, we discuss how cross-reactive T cell responses may be useful in generating a broad adaptive immunity, recognizing different variants and viral families. Considering vaccines with broadly conserved antigens could improve preparedness for future infectious disease outbreaks.
Leaving the hospital on time: hospital bed utilization and reasons for discharge delay in the Netherlands
Authors: van den Ende Eva , Schouten Bo , Pladet Lara , Merten Hanneke , van Galen Louise , Marinova Milka , Schinkel Michiel , Boerman Anneroos W , Nannan Panday Rishi , Rustemeijer Cees , Dulaimy Muhammad , Bell Derek , Nanayakkara Prabath Wb
Published: May 2023

Inappropriate bed occupancy due to delayed hospital discharge affects both physical and psychological well-being in patients and can disrupt patient flow. The Dutch healthcare system is facing ongoing pressure, especially during the current coronavirus disease pandemic, intensifying the need for optimal use of hospital beds. The aim of this study was to quantify inappropriate patient stays and describe the underlying reasons for the delays in discharge. The Day of Care Survey (DoCS) is a validated tool used to gain information about appropriate and inappropriate bed occupancy in hospitals. Between February 2019 and January 2021, the DoCS was performed five times in three different hospitals within the region of Amsterdam, the Netherlands. All inpatients were screened, using standardized criteria, for their need for in-hospital care at the time of survey and reasons for discharge delay. A total of 782 inpatients were surveyed. Of these patients, 94 (12%) were planned for definite discharge that day. Of all other patients, 145 (21%, ranging from 14% to 35%) were without the need for acute in-hospital care. In 74% (107/145) of patients, the reason for discharge delay was due to issues outside the hospital; most frequently due to a shortage of available places in care homes (26%, 37/145). The most frequent reason for discharge delay inside the hospital was patients awaiting a decision or review by the treating physician (14%, 20/145). Patients who did not meet the criteria for hospital stay were, in general, older [median 75, interquartile range (IQR) 65–84 years, and 67, IQR 55–75 years, respectively, P < .001] and had spent more days in hospital (7, IQR 5–14 days, and 3, IQR 1–8 days respectively, P < .001). Approximately one in five admitted patients occupying hospital beds did not meet the criteria for acute in-hospital stay or care at the time of the survey. Most delays were related to issues outside the immediate control of the hospital. Improvement programmes working with stakeholders focusing on the transfer from hospital to outside areas of care need to be further developed and may offer potential for the greatest gain. The DoCS can be a tool to periodically monitor changes and improvements in patient flow.
‘If you want to go far, go together’—community-based behaviour change interventions to improve antibiotic use: a systematic review of quantitative and qualitative evidence
Authors: Ghiga Ioana , Sidorchuk Anna , Pitchforth Emma , Stålsby Lundborg Cecilia , Machowska Anna
Published: May 2023

Introduction

A large proportion of the burden of infections with antibiotic-resistant bacteria is linked to community-associated infections. This suggests that interventions set in community settings are needed. Currently there is a gap in understanding the potential of such interventions across all geographies. This systematic review aimed to synthesize the evidence on the value of community-based behaviour change interventions to improve antibiotic use. These are any interventions or innovations to services intended to stimulate behaviour changes among the public towards correct antibiotic use, delivered in a community setting and online.

Methods

Systematic searches of studies published after 2001 were performed in several databases. Of 14 319 articles identified, 73 articles comprising quantitative, qualitative and mixed-methods studies met the inclusion criteria.

Results

Findings showed positive emerging evidence of the benefits of community-based behaviour change interventions to improve antibiotic use, with multifaceted interventions offering the highest benefit. Interventions that combine educational aspects with persuasion may be more effective than solely educational interventions. The review uncovered difficulties in assessing this type of research and highlights the need for standardized approaches in study design and outcomes measurements. There is emerging, but limited, indication on these interventions’ cost-effectiveness.

Conclusions

Policy makers should consider the potential of community-based behaviour change interventions to tackle antimicrobial resistance (AMR), complementing the clinical-based approaches. In addition to the direct AMR benefits, these could serve also as a means of (re)building trust, due to their inclusive participation leading to greater public ownership and use of community channels.
Pharmacokinetics comparison of vardenafil as administered by an intranasal spray formulation vs a 10-mg oral tablet
Authors: Wang Jeffrey , Chow Sheryl L , Chow Moses S S , Paik Amy , Louie Stan G , Dong Fanglong , Sathananthan Airani , White Stephanie
Published: May 2023

Background

Oral vardenafil (VDF) tablet is an effective treatment for erectile dysfunction (ED), but intranasal administration with a suitable formulation can lead to a faster onset of action and offer more convenient planning for ED treatment.

Aim

The primary purpose of the present pilot clinical study was to determine whether intranasal VDF with an alcohol-based formulation can result in more “user-friendly pharmacokinetics” as compared with oral tablet administration.

Methods

This single-dose randomized crossover study was conducted in 12 healthy young volunteers receiving VDF as a 10-mg oral tablet or 3.38-mg intranasal spray. Multiple blood concentrations were obtained, and VDF concentrations were determined with a liquid chromatography–tandem mass spectrometry assay. Pharmacokinetic parameters following each treatment were compared and adverse events assessed.

Outcomes

Pharmacokinetic parameters were obtained: apparent elimination rate constant, elimination half-life, peak concentration, peak time, total area under the curve, and relative bioavailability.

Results

Although mean apparent elimination rate constant, elimination half-life, peak concentration, and total area under the curve were similar between intranasal and oral administration, the median peak time from intranasal was much shorter (10 vs 58 minutes, P < .001, Mann-Whitney U test). The variability of the pharmacokinetic parameters was also less with intranasal than oral administration. The relative bioavailability of intranasal to oral was 1.67. Intranasal VDF caused transient but tolerable local nasal reactions in 50% of subjects. Other adverse events (eg, headache) were similar between the treatments. The incidence of adverse events was, however, significantly less in the second treatment after initial exposure to VDF. No serious adverse events were noted.

Clinical Implications

Intranasal VDF potentially offers a more timely and lower dose for the treatment of ED in patients who can tolerate the transient local adverse reactions.

Strengths and Limitations

The strength of this study is its randomized crossover design. Because the study was conducted in 12 healthy young subjects, the results may not reflect those observed in elderly patients who may be likely taking VDF for ED. Nevertheless, the changes of pharmacokinetic parameters in the present study are likely a reflection of the differences between intranasal and oral administration of the formulations.

Conclusion

Our study indicated that the present VDF formulation, when administered intranasally, can achieve a more rapid but similar plasma concentration with only about one-third dose when compared with the oral administration.
Unsigned magnetic flux proxy from solar optical intensity spectra
Authors: Lienhard F , Mortier A , Cegla H M , Cameron A Collier , Klein B , Watson C A
Published: May 2023

The photospheric unsigned magnetic flux has been shown to be highly correlated with radial velocity (RV) variations caused by solar surface activity. This activity indicator is therefore a prime candidate to unlock the potential of RV surveys to discover Earth twins orbiting Sun-like stars. We show for the first time how a precise proxy of the unsigned magnetic flux (ΔαB2) can be obtained from Sun-as-a-star intensity spectra by harnessing the magnetic information contained in over 4000 absorption lines in the wavelength range from 380 to 690 nm. This novel activity proxy can thus be obtained from the same spectra from which RVs are routinely extracted. We derived  ΔαB2 from 500 randomly selected spectra from the HARPS-N public solar data set, which spans from 2015 to 2018. We compared our estimates with the unsigned magnetic flux values from the Solar Dynamics Observatory (SDO) finding excellent agreement (median absolute deviation: 4.9 per cent). The extracted indicator  ΔαB2 correlates with SDO’s unsigned magnetic flux estimates on the solar rotational time-scale (Pearson correlation coefficient 0.67) and on the 3-yr time-scale of our data set (correlation coefficient 0.91). We find correlations of  ΔαB2 with the HARPS-N solar RV variations of 0.49 on the rotational time-scale and 0.78 on the 3-yr time-scale. The Pearson correlation of  ΔαB2 with the RVs is found to be greater than the correlation of the classical activity indicators with the RVs. For solar-type stars,  ΔαB2 therefore represents the best simultaneous activity proxy known to date.
Fundamental cosmology from ANDES precision spectroscopy
Authors: Marques C M J , Martins C J A P , Alves C S
Published: May 2023

Fundamental cosmology observations, such as the detection of the redshift drift and tests of the universality of physical laws, are key science and design drivers of the ArmazoNes high Dispersion Echelle Spectrograph (ANDES), an Extremely Large Telescope instrument. While separate forecasts for each of them have been reported, we have developed Fisher matrix based forecast tools combining both of these observables. We demonstrate the synergies between the two ANDES data sets, quantifying the improvements in cosmology and fundamental physics parameter constraints for two separate theoretical paradigms. We publicly release this forecast code, which is one of the tools for the optimization of the ANDES observing strategy.
Overmassive central black holes in the cosmological simulations astrid and Illustris TNG50
Authors: Weller Emma Jane , Pacucci Fabio , Natarajan Priyamvada , Di Matteo Tiziana
Published: May 2023

Recent dynamical measurements indicate the presence of a central supermassive black hole (SMBH) with mass ${\sim} 3\times 10^6\, {\rm M_\odot }$ in the dwarf galaxy Leo I, placing the system ∼50 times above the standard, local MBH–M⋆ relation. While a few overmassive central SMBHs are reported in nearby isolated galaxies, this is the first one detected in a Milky Way satellite. We used the ASTRID and Illustris TNG50 lambda cold dark matter (LCDM) cosmological simulations to investigate the assembly history of galaxies hosting overmassive SMBHs. We estimate that, at the stellar mass of Leo I, ${\sim} 15~{{\ \rm per\ cent}}$ of galaxies above the MBH–M⋆ relation lie >10 times above it. Leo I-like systems are rare but exist in LCDM simulations: they occur in ${\sim} 0.005~{{\ \rm per\ cent}}$ of all overmassive systems. Examining the properties of simulated galaxies harbouring overmassive central SMBHs, we find that: (i) stars assemble more slowly in galaxies above the MBH–M⋆ relation; (ii) the gas fraction in these galaxies experiences a significantly steeper decline over time; and (iii) $\gt 95~{{\ \rm per\ cent}}$ of satellite host galaxies in overdense regions are located above the MBH–M⋆ relation. This suggests that massive satellite infall and consequent tidal stripping in a group/dense environment can drive systems away from the MBH–M⋆ relation, causing them to become overmassive. As the merging histories of overmassive and undermassive systems do not differ, we conclude that additional environmental effects, such as being in overdense regions must play a crucial role. In the high-z Universe, central overmassive SMBHs are a signature of heavy BH seeds; we demonstrate, in contrast, that low-z overmassive systems result from complex environmental interactions.
Deviations from spherical shape decrease the growth velocity in granular aggregate collisions – a granular mechanics study
Authors: Bandyopadhyay Rahul , Urbassek Herbert M
Published: May 2023

We used granular mechanics simulations to study collisions between spherical aggregates and axisymmetric ellipsoidal aggregates of equal mass. Non-spherical aggregates may be generated, for example, as the result of previous aggregate collisions, either from the merging of aggregates or from fragmentation processes. Of particular interest is the growth velocity, i.e. the critical collision velocity above which the size of the largest post-collision fragment is smaller than the original aggregate size. We find a systematic decrease of the growth velocity with axis ratio of the ellipsoid. The decrease is caused by the ‘rim peel-off’ effect: grain material close to the rims is more readily ejected from the boundaries of aggregates. When considering collisions with ellipsoids of identical semimajor axis, the growth velocity of oblate ellipsoids surpasses that of prolate ellipsoids. Averaging over the orientation of the ellipsoid and over the impact parameters possible in a collision retains the above-mentioned results. The influence of aggregate shape on collision outcomes is of interest, for instance, for codes describing the evolution of dust clouds under collisions.