bluuebunny/crossref_metadata_2025 huggingface dataset:
The Russian world order before and after the Ukraine War
Authors: Hansen Flemming Splidsboel
Published: February 2023

For many years, the political debate in Russia has contained an element about a coming world order. There has been a general agreement that the state of affairs following the end of the Cold War was untenable, and that something different and more durable would replace the alleged US-led order. This debate has become more acute following Russia’s invasion of Ukraine on 24 February 2022. In the aftermath of the invasion, Russian president Vladimir Putin has reached out to the Global South in particular, and he has spoken about a more democratic, inclusive, and respectful order on numerous occasions. It is difficult to assess, however, to which extent his promises are caused by a need to forge new alliances, and to which extent Moscow is actually willing to reform for instance the UN system and allow the states in the Global South more influence.
Successor-like representation guides the prediction of future events in human visual cortex and hippocampus
Authors: Ekman Matthias , Kusch Sarah , de Lange Floris P
Published: February 2023

Human agents build models of their environment, which enable them to anticipate and plan upcoming events. However, little is known about the properties of such predictive models. Recently, it has been proposed that hippocampal representations take the form of a predictive map-like structure, the so-called successor representation (SR). Here, we used human functional magnetic resonance imaging to probe whether activity in the early visual cortex (V1) and hippocampus adhere to the postulated properties of the SR after visual sequence learning. Participants were exposed to an arbitrary spatiotemporal sequence consisting of four items (A-B-C-D). We found that after repeated exposure to the sequence, merely presenting single sequence items (e.g., - B - -) resulted in V1 activation at the successor locations of the full sequence (e.g., C-D), but not at the predecessor locations (e.g., A). This highlights that visual representations are skewed toward future states, in line with the SR. Similar results were also found in the hippocampus. Moreover, the hippocampus developed a coactivation profile that showed sensitivity to the temporal distance in sequence space, with fading representations for sequence events in the more distant past and future. V1, in contrast, showed a coactivation profile that was only sensitive to spatial distance in stimulus space. Taken together, these results provide empirical evidence for the proposition that both visual and hippocampal cortex represent a predictive map of the visual world akin to the SR.
Arginase 1 is a key driver of immune suppression in pancreatic cancer
Authors: Menjivar Rosa E , Nwosu Zeribe C , Du Wenting , Donahue Katelyn L , Hong Hanna S , Espinoza Carlos , Brown Kristee , Velez-Delgado Ashley , Yan Wei , Lima Fatima , Bischoff Allison , Kadiyala Padma , Salas-Escabillas Daniel , Crawford Howard C , Bednar Filip , Carpenter Eileen , Zhang Yaqing , Halbrook Christopher J , Lyssiotis Costas A , Pasca di Magliano Marina
Published: February 2023

An extensive fibroinflammatory stroma rich in macrophages is a hallmark of pancreatic cancer. In this disease, it is well appreciated that macrophages are immunosuppressive and contribute to the poor response to immunotherapy; however, the mechanisms of immune suppression are complex and not fully understood. Immunosuppressive macrophages are classically defined by the expression of the enzyme Arginase 1 (ARG1), which we demonstrated is potently expressed in pancreatic tumor-associated macrophages from both human patients and mouse models. While routinely used as a polarization marker, ARG1 also catabolizes arginine, an amino acid required for T cell activation and proliferation. To investigate this metabolic function, we used a genetic and a pharmacologic approach to target Arg1 in pancreatic cancer. Genetic inactivation of Arg1 in macrophages, using a dual recombinase genetically engineered mouse model of pancreatic cancer, delayed formation of invasive disease, while increasing CD8+ T cell infiltration. Additionally, Arg1 deletion induced compensatory mechanisms, including Arg1 overexpression in epithelial cells, namely Tuft cells, and Arg2 overexpression in a subset of macrophages. To overcome these compensatory mechanisms, we used a pharmacological approach to inhibit arginase. Treatment of established tumors with the arginase inhibitor CB-1158 exhibited further increased CD8+ T cell infiltration, beyond that seen with the macrophage-specific knockout, and sensitized the tumors to anti-PD1 immune checkpoint blockade. Our data demonstrate that Arg1 drives immune suppression in pancreatic cancer by depleting arginine and inhibiting T cell activation.
Coordinated evolution at amino acid sites of SARS-CoV-2 spike
Authors: Neverov Alexey Dmitrievich , Fedonin Gennady , Popova Anfisa , Bykova Daria , Bazykin Georgii
Published: February 2023

SARS-CoV-2 has adapted in a stepwise manner, with multiple beneficial mutations accumulating in a rapid succession at origins of VOCs, and the reasons for this are unclear. Here, we searched for coordinated evolution of amino acid sites in the spike protein of SARS-CoV-2. Specifically, we searched for concordantly evolving site pairs (CSPs) for which changes at one site were rapidly followed by changes at the other site in the same lineage. We detected 46 sites which formed 45 CSP. Sites in CSP were closer to each other in the protein structure than random pairs, indicating that concordant evolution has a functional basis. Notably, site pairs carrying lineage defining mutations of the four VOCs that circulated before May 2021 are enriched in CSPs. For the Alpha VOC, the enrichment is detected even if Alpha sequences are removed from analysis, indicating that VOC origin could have been facilitated by positive epistasis. Additionally, we detected nine discordantly evolving pairs of sites where mutations at one site unexpectedly rarely occurred on the background of a specific allele at another site, for example on the background of wild-type D at site 614 (four pairs) or derived Y at site 501 (three pairs). Our findings hint that positive epistasis between accumulating mutations could have delayed the assembly of advantageous combinations of mutations comprising at least some of the VOCs.
Window films increase avoidance of collisions by birds but only when applied to external compared with internal surfaces of windows
Authors: Swaddle John P. , Brewster Blythe , Schuyler Maddie , Su Anjie
Published: February 2023

Window collisions are one of the largest human-caused causes of avian mortality in built environments and, therefore, cause population declines that can be a significant conservation issue. Applications of visibly noticeable films, patterns, and decals on the external surfaces of windows have been associated with reductions in both window collisions and avian mortality. It is often logistically difficult and economically prohibitive to apply these films and decals to external surfaces, especially if the windows are above the first floor of a building. Therefore, there is interest and incentive to apply the products to internal surfaces that are much easier to reach and maintain. However, there is debate as to whether application to the internal surface of windows renders any collision-reduction benefit, as the patterns on the films and decals may not be sufficiently visible to birds. To address this knowledge gap, we performed the first experimental study to compare the effectiveness of two distinct window films when applied to either the internal or external surface of double-glazed windows. Specifically, we assessed whether Haverkamp and BirdShades window film products were effective in promoting the avoidance of window collisions (and by inference, a reduction of collisions) by zebra finches through controlled aviary flight trials employing a repeated-measures design that allowed us to isolate the effect of the window treatments on avoidance flight behaviors. We chose these two products because they engage with different wavelengths of light (and by inference, colors) visible to many songbirds: the BirdShades film is visible in the ultraviolet (shorter wavelength) range, while the Haverkamp film includes signals in the orange (longer wavelength) range. We found consistent evidence that, when applied to the external surface of windows, the BirdShades product resulted in reduced likelihood of collision and there was marginal evidence of this effect with the Haverkamp film. Specifically, in our collision avoidance trials, BirdShades increased window avoidance by 47% and the Haverkamp increased avoidance by 39%. However, neither product was effective when the films were applied to the internal surface of windows. Hence, it is imperative that installers apply these products to exterior surfaces of windows to render their protective benefits and reduce the risk of daytime window collision.
Density regulation amplifies environmentally induced population fluctuations
Authors: Mutshinda Crispin M. , Mishra Aditya , Finkel Zoe V. , Irwin Andrew J.
Published: February 2023

Background

Density-dependent regulation is ubiquitous in population dynamics, and its potential interaction with environmental stochasticity complicates the characterization of the random component of population dynamics. Yet, this issue has not received attention commensurate with its relevance for descriptive and predictive modeling of population dynamics. Here we use a Bayesian modeling approach to investigate the contribution of density regulation to population variability in stochastic environments.

Methods

We analytically derive a formula linking the stationary variance of population abundance/density under Gompertz regulation in a stochastic environment with constant variance to the environmental variance and the strength of density feedback, to investigate whether and how density regulation affects the stationary variance. We examine through simulations whether the relationship between stationary variance and density regulation inferred analytically under the Gompertz model carries over to the Ricker model, widely used in population dynamics modeling.

Results

The analytical decomposition of the stationary variance under stochastic Gompertz dynamics implies higher variability for strongly regulated populations. Simulation results demonstrate that the pattern of increasing population variability with increasing density feedback found under the Gompertz model holds for the Ricker model as well, and is expected to be a general phenomenon with stochastic population models. We also analytically established and empirically validated that the square of the autoregressive parameter of the Gompertz model in AR(1) form represents the proportion of stationary variance due to density dependence.

Discussion

Our results suggest that neither environmental stochasticity nor density regulation can alone explain the patterns of population variability in stochastic environments, as these two components of temporal variation interact, with a tendency for density regulation to amplify the magnitude of environmentally induced population fluctuations. This finding has far-reaching implications for population viability. It implies that intense intra-specific resource competition increases the risk of environment-driven population collapse at high density, making opportune harvesting a sensible practice for improving the resistance of managed populations such as fish stocks to environmental perturbations. The separation of density-dependent and density-independent processes will help improve population dynamics modeling, while providing a basis for evaluating the relative importance of these two categories of processes that remains a topic of long-standing controversy among ecologists.
Repeatability of an attention bias test for sheep suggests variable influence of state and trait affect on behaviour
Authors: Monk Jessica E. , Colditz Ian G. , Clark Sam , Lee Caroline
Published: February 2023

Understanding the effects of repeated testing on behaviour is essential for behavioural tests that are re-applied to the same individuals for research and welfare assessment purposes. Assessing the repeatability of behaviour can also help us understand the influence of persistent traits vs transient states on animal responses during testing. This study examined the repeatability of behavioural responses in an attention bias test developed for sheep as a measure of affective state. Sheep were assessed in the attention bias test three times (n = 81 sheep), with testing occurring at intervals of 1 year then 2 weeks. During testing, individual sheep were exposed to a dog located behind a window for 3 s in a 4 × 4 m arena, then the dog was obscured from view, removed and sheep behaviours were recorded for 180 s. We hypothesised that behaviours in the test would have moderate-high repeatability but that the mean behavioural responses would change over consecutive trials as sheep habituated to the test environment. To estimate repeatability, data were modelled using restricted maximum likelihood linear mixed-effects models, fitting animal ID as a random effect. Vigilance behaviour, defined as having the head at or above shoulder height, was moderately repeatable (r = 0.58). Latency to eat (r = 0.20) and duration spent looking towards the previous location of the dog (attention to the dog wall) (r = 0.08) had low repeatability. Mean latency to eat did not differ significantly between trials (P = 0.2) and mean vigilance behaviour tended to decrease over the trials (P = 0.07). Mean duration of attention to the dog wall significantly decreased across the trials (P < 0.001), while mean zones crossed increased (P < 0.001), as did behaviours directed towards the exit door such as duration in proximity and pawing at the door. Overall, vigilance behaviour was moderately repeatable, suggesting it may have been driven by temperament or personality traits, while attention and feeding behaviours may have been more influenced by transient affective states or other factors, however further research is needed to better tease apart these potential effects. Sheep demonstrated some habituation to the test over consecutive trials. Care should therefore be taken during future application of the test to ensure all animals undergoing attention bias testing have equivalent experience for a valid interpretation of their relative behavioural responses.
Establishment and verification of a nomogram model for predicting the risk of post-stroke depression
Authors: Luo Shihang , Zhang Wenrui , Mao Rui , Huang Xia , Liu Fan , Liao Qiao , Sun Dongren , Chen Hengshu , Zhang Jingyuan , Tian Fafa
Published: February 2023

Objective

The purpose of this study was to establish a nomogram predictive model of clinical risk factors for post-stroke depression (PSD).

Patients and Methods

We used the data of 202 stroke patients collected from Xuanwu Hospital from October 2018 to September 2020 as training data to develop a predictive model. Nineteen clinical factors were selected to evaluate their risk. Minimum absolute contraction and selection operator (LASSO, least absolute shrinkage and selection operator) regression were used to select the best patient attributes, and seven predictive factors with predictive ability were selected, and then multi-factor logistic regression analysis was carried out to determine six predictive factors and establish a nomogram prediction model. The C-index, calibration chart, and decision curve analyses were used to evaluate the predictive ability, accuracy, and clinical practicability of the prediction model. We then used the data of 156 stroke patients collected by Xiangya Hospital from June 2019 to September 2020 for external verification.

Results

The selected predictors including work style, number of children, time from onset to hospitalization, history of hyperlipidemia, stroke area, and the National Institutes of Health Stroke Scale (NIHSS) score. The model showed good prediction ability and a C index of 0.773 (95% confidence interval: [0.696–0.850]). It reached a high C-index value of 0.71 in bootstrap verification, and its C index was observed to be as high as 0.702 (95% confidence interval: [0.616–0.788]) in external verification. Decision curve analyses further showed that the nomogram of post-stroke depression has high clinical usefulness when the threshold probability was 6%.

Conclusion

This novel nomogram, which combines patients’ work style, number of children, time from onset to hospitalization, history of hyperlipidemia, stroke area, and NIHSS score, can help clinicians to assess the risk of depression in patients with acute stroke much earlier in the timeline of the disease, and to implement early intervention treatment so as to reduce the incidence of PSD.
What Is Guillain-Barré Syndrome?
Authors: Marcus Revital
Published: February 2023

This JAMA Patient Page describes the autoimmune disease Guillain-Barré syndrome and its risk factors, diagnosis, treatment, and prognosis.
Rates of and Factors Associated With Primary and Booster COVID-19 Vaccine Receipt by US Veterans, December 2020 to June 2022
Authors: Bajema Kristina L. , Rowneki Mazhgan , Berry Kristin , Bohnert Amy , Bowling C. Barrett , Boyko Edward J. , Iwashyna Theodore J. , Maciejewski Matthew L. , O’Hare Ann M. , Osborne Thomas F. , Viglianti Elizabeth M. , Hynes Denise M. , Ioannou George N.
Published: February 2023

Importance

COVID-19 vaccination rates remain suboptimal in the US. Identifying factors associated with vaccination can highlight existing gaps and guide targeted interventions to improve vaccination access and uptake.

Objective

To describe incidence and patient characteristics associated with primary, first booster, and second booster COVID-19 vaccination in the Veterans Health Administration (VHA).

Design, Setting, and Participants

This retrospective cohort study assessed US veterans receiving care in VHA medical centers and outpatient clinics as of December 1, 2020. All VHA enrollees with an inpatient, outpatient, or telehealth encounter in VHA as well as a primary care physician appointment in the preceding 24 months were included.

Exposures

Demographic characteristics, place of residence, prior SARS-CoV-2 infection, and underlying medical conditions.

Main Outcomes and Measures

Cumulative incidence of primary, first booster, and second booster COVID-19 vaccination through June 2022. Cox proportional hazards regression was used to identify factors independently associated with COVID-19 vaccination.

Results

Among 5 632 413 veterans included in the study, 5 094 392 (90.4%) were male, the median (IQR) age was 66 (51-74) years, 1 032 334 (18.3%) were Black, 448 714 (8.0%) were Hispanic, and 4 202 173 (74.6%) were White. Through June 2022, cumulative incidences were 69.0% for primary vaccination, 42.9% for first booster, and 9.3% for second booster. Cumulative incidence for primary vaccination increased with increasing age, from 46.9% (95% CI, 46.8%-47.0%) among veterans aged 18 to 49 years to 82.9% (95% CI, 82.8%-83.0%) among veterans aged 80 to 84 years. More Black veterans completed primary vaccination (71.7%; 95% CI, 71.6%-71.8%) compared with White veterans (68.9%; 95% CI, 68.9%-69.0%), and more urban-dwelling veterans completed primary vaccination (70.9%; 95% CI, 70.9%-71.0%) compared with highly rural-dwelling veterans (63.8%; 95% CI, 63.4%-64.1%). Factors independently associated with higher likelihood of both primary and booster vaccination included older age, female sex, Asian or Black race, Hispanic ethnicity, urban residence, and lack of prior SARS-CoV-2 infection.

Conclusions and Relevance

In this cohort study of US veterans, COVID-19 vaccination coverage through June 2022 was suboptimal. Primary vaccination can be improved among younger, rural-dwelling veterans. Greater uptake of booster vaccination among all veterans is needed.
A Nearly Obstructive Intratracheal Mass in a Pediatric Patient
Authors: Hakimi Amir A. , Orobello Nicklas C. , Mudd Pamela A.
Published: February 2023

A 12-year-old girl presented to the clinic with a 3-month history of intermittent stridor; her symptoms were initially most prominent while playing sports and were suspected to be due to asthma or seasonal allergies. What is your diagnosis?
Exportin 1‐mediated nuclear/cytoplasmic trafficking controls drug sensitivity of classical Hodgkin's lymphoma
Authors: Caillot Mélody , Miloudi Hadjer , Taly Antoine , Profitós‐Pelejà Nuria , Santos Juliana C. , Ribeiro Marcelo L. , Maitre Elsa , Saule Simon , Roué Gaël , Jardin Fabrice , Sola Brigitte
Published: February 2023

Exportin 1 (XPO1) is the main nuclear export receptor that controls the subcellular trafficking and the functions of major regulatory proteins. XPO1 is overexpressed in various cancers and small inhibitors of nuclear export (SINEs) have been developed to inhibit XPO1. In primary mediastinal B‐cell lymphoma (PMBL) and classical Hodgkin's lymphoma (cHL), the XPO1 gene may be mutated on one nucleotide and encodes the mutant XPO1E571K. To understand the impact of mutation on protein function, we studied the response of PMBL and cHL cells to selinexor, a SINE, and ibrutinib, an inhibitor of Bruton tyrosine kinase. XPO1 mutation renders lymphoma cells more sensitive to selinexor due to a faster degradation of mutant XPO1 compared to the wild‐type. We further showed that a mistrafficking of p65 (RELA) and p52 (NFκB2) transcription factors between the nuclear and cytoplasmic compartments accounts for the response toward ibrutinib. XPO1 mutation may be envisaged as a biomarker of the response of PMBL and cHL cells and other B‐cell hemopathies to SINEs and drugs that target even indirectly the NFκB signaling pathway.
Qualitative Interviews to Assess the Content Validity and Usability of the Electronic Raynaud Diary in Patients with Systemic Sclerosis
Authors: Domsic Robyn T. , Pokrzywinski Robin , Stassek Larissa , Benton Wade W. , Vampola Christa‐Lynn , Furst Daniel E. , Chung Lorinda , Steen Virginia , Mayes Maureen D. , Shah Ami A. , Molitor Jerry A. , Oliver Kelly , Nagaraja Vivek , Khanna Dinesh
Published: February 2023

Objective

To better understand the symptoms and impacts of Raynaud phenomenon (RP) in patients with systemic sclerosis (SSc) and to evaluate the content validity and usability of a new electronic patient‐reported outcome (PRO) measure for RP: the Raynaud Diary.

Methods

The Raynaud Diary was developed as a daily eDiary for assessing the number and duration of symptomatic Raynaud attacks; worst pain, numbness, tingling, and discomfort in the fingers; and overall disease severity, captured using the Raynaud's Condition Score. The Raynaud Diary was debriefed in two waves of qualitative interviews with adults with self‐reported RP secondary to SSc. All interviews included open‐ended questions about participants' experiences of RP.

Results

Participants (N = 39) had a mean age of 55.1 years, and 87% were female. Frequently reported RP symptoms were color change (reported by all participants), numbness (90%), tingling (82%), pain (77%), and discomfort (72%). Common attack triggers included temperature‐related factors and stress. Participants reported being unable to be outside or do outdoor activities and had problems gripping objects. All participants demonstrated understanding of the Raynaud Diary instructions. Most participants indicated that they would be able to use the Raynaud Diary to record the worst severity of individual RP symptoms in the previous 24 hours.

Conclusion

Patients with RP secondary to SSc bear a heavy symptom burden. The Raynaud Diary is a content valid PRO measure that captures the most frequent symptoms of RP in patients with SSc.
Higher‐Order Topological States in Thermal Diffusion
Authors: Wu Haotian , Hu Hao , Wang Xixi , Xu Zhixia , Zhang Baile , Wang Qi Jie , Zheng Yuanjin , Zhang Jingjing , Cui Tie Jun , Luo Yu
Published: February 2023

Unlike conventional topological materials that carry topological states at their boundaries, higher‐order topological materials are able to support topological states at boundaries of boundaries, such as corners and hinges. While band topology has been recently extended into thermal diffusion for thermal metamaterials, its realization is limited to a 1D thermal lattice, lacking access to the higher‐order topology. In this work, the experimental realization is reported of a higher‐order thermal topological insulator in a generalized 2D diffusion lattice. The topological corner states for thermal diffusion are observed in the bandgap of diffusion rate of the bulk, as a consequence of the anti‐Hermitian nature of the diffusion Hamiltonian. The topological protection of these thermal corner states is demonstrated with the stability of their diffusion profile in the presence of amorphous deformation. This work constitutes the first realization of higher‐order topology in purely diffusive systems and opens the door for future thermal management with topological protection beyond 1D geometries.
Molecular Engineering for Chiroptical Smart Paints: Photo‐Tunable and Polymerizable Helical Nanostructures by Cyanostilbene‐Based Reactive Mesogens
Authors: Koo Jahyeon , Jang Junhwa , Kim Minwook , Hyeong Jaeseok , Yu Dongmin , Rim Minwoo , Ko Hyeyoon , Lim Seok‐In , Kim Dae‐Yoon , Jeong Kwang‐Un
Published: February 2023

Many studies on the basis of cholesteric liquid crystal (CLC) have focused on dynamic optical changes utilizing photochemical reactions raising helical pitch variations. However, the conventional dyes doped in CLC system often show reversible isomerization such as trans‐cis, E‐Z, and open‐close forms that hampers the fixation of desired color cues. Here, a cyanostilbene‐based reactive mesogen (CSRM) for phototunable and subsequently polymerizable smart CLC paints is newly designed and synthesized. The structural color of the CLC paint can be precisely manipulated in remote controllable manner by inducing a photochemical reaction of CSRM. Due to the irreversible isomerization behaviors of CSRM, the constructed periodic structures with different helical pitches are intactly fixed via in situ photopolymerization under 460 nm light. In addition, the combination of helical nanostructures and cyanostilbene luminophore produces a circularly polarized light emission. The dissymmetry factor of circularly polarized luminescence is dependent on the photoregulated helical nanostructures in CLC films. The decoupled system of triple photofunctionality in a single component of chirophotonic crystalline material is applied to develop advanced optical information storages.
Effect of Additives in the Hydroamination/Cyclization of Aminoalkenes Catalyzed by a Binaphtholate Yttrium Catalyst
Authors: Nawara‐Hultzsch Agnieszka J. , Goswami Anandarup , Hultzsch Kai C.
Published: February 2023

A series of various solvents and additives were tested in enantioselective hydroamination/cyclization reactions of aminoalkenes catalyzed by a binaphtholate yttrium catalyst. The functional group tolerance of the catalyst and the influence on the reaction rate and enantioselectivity was studied. Some weakly coordinating polar solvents, such as Et2O, MTBE, and chlorobenzene led to slightly increased reaction rates compared to the less polar solvent benzene, presumably due to a better stabilization of the polar transition state. Stronger binding solvents and additives, such as THF, DMAP, pyrrolidine, n‐propylamine, and 1‐phenylethylamine, decrease the reaction rate and diminish the enantioselectivity of the hydroamination product. Some additives, such as THF, Et2O, MTBE, chloro‐ and bromobenzene, as well as (+)‐sparteine resulted in slightly higher enantioselectivities in the cyclization of the model substrate C‐(1‐allylcyclohexyl)methylamine, although this observation was not generally true for other aminoalkene substrates. The reaction rates and enantioselectivities were depressed in the presence of (−)‐sparteine using the (R)‐binaphtholate‐ligated catalyst. In case of C‐(1‐allylcyclohexyl)methylamine, the enantioselectivity was switched from 76% ee favoring the (S)‐enantiomer of the hydroamination product when using (+)‐sparteine to 22% ee in favor of the (R)‐enantiomer when (−)‐sparteine was used. The rates of cyclization of aminoalkenes and the resulting enantioselectivities significantly depend on substrate concentration with the highest rate (13.6 h−1) and enantioselectivity (68% ee) observed in dilute conditions (0.05 M) compared to a concentrated solution (0.5 M, 5.0 h−1, 35% ee) for 2,2‐dimethylpent‐4‐enylamine. These observations indicate that the reaction mechanism is shifted in favor of a slower, less enantioselective catalytic cycle involving a higher coordinate species when higher substrate concentrations or stronger binding additives are present.

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Vascular Cast to Program Antistenotic Hemodynamics and Remodeling of Vein Graft
Authors: Ha Hyunsu , Park Ju Young , Lee Chan Hee , Son Deok‐Hyeon , Chung Soon Won , Baek Sewoom , Lee Kyubae , Lee Kang Suk , Yi Se Won , Kang Mi‐Lan , Kim Dae‐Hyun , Sung Hak‐Joon
Published: February 2023

The structural stability of medical devices is established by managing stress distribution in response to organ movement. Veins abruptly dilate upon arterial grafting due to the mismatched tissue property, resulting in flow disturbances and consequently stenosis. Vascular cast is designed to wrap the vein‐artery grafts, thereby adjusting the diameter and property mismatches by relying on the elastic fixity. Here, a small bridge connection in the cast structure serves as an essential element to prevent stress concentrations due to the improved elastic fixity. Consequently, the vein dilation is efficiently suppressed, healthy (laminar and helical) flow is induced effectively, and the heathy functions of vein grafting are promoted, as indicated by the flow directional alignment of endothelial cells with arterialization, muscle expansion, and improved contractility. Finally, collaborative effects of the bridge drastically suppress stenosis with patency improvement. As a key technical point, the advantages of the bridge addition are validated via the computational modeling of fluid–structure interaction, followed by a customized ex vivo set‐up and analyses. The calculated effects are verified using a series of cell, rat, and canine models towards translation. The bridge acted like “Little Dutch boy” who saved the big mass using one finger by supporting the cast function.
Engineered Sensory Nerve Guides Self‐Adaptive Bone Healing via NGF‐TrkA Signaling Pathway
Authors: Zhang Zengjie , Wang Fangqian , Huang Xin , Sun Hangxiang , Xu Jianxiang , Qu Hao , Yan Xiaobo , Shi Wei , Teng Wangsiyuan , Jin Xiaoqiang , Shao Zhenxuan , Zhang Yongxing , Zhao Shenzhi , Wu Yan , Ye Zhaoming , Yu Xiaohua
Published: February 2023

The upstream role of sensory innervation during bone homeostasis is widely underestimated in bone repairing strategies. Herein, a neuromodulation approach is proposed to orchestrate bone defect healing by constructing engineered sensory nerves (eSN) in situ to leverage the adaptation feature of SN during tissue formation. NGF liberated from ECM‐constructed eSN effectively promotes sensory neuron differentiation and enhances CGRP secretion, which lead to improved RAOECs mobility and osteogenic differentiation of BMSC. In turn, such eSN effectively drives ossification in vivo via NGF‐TrkA signaling pathway, which substantially accelerates critical size bone defect healing. More importantly, eSN also adaptively suppresses excessive bone formation and promotes bone remodeling by activating osteoclasts via CGRP‐dependent mechanism when combined with BMP‐2 delivery, which ingeniously alleviates side effects of BMP‐2. In sum, this eSN approach offers a valuable avenue to harness the adaptive role of neural system to optimize bone homeostasis under various clinical scenario.
In vitro digestion and fermentation of Japanese macaque (Macaca fuscata) food: The influence of food type and particle size
Authors: He Tianmeng , Lee Wanyi , Hanya Goro
Published: February 2023

Chewing is critical for herbivores to obtain nutrients. Measuring digesta particle size as the outcome of chewing can improve our understanding of the relationship between food and digestion. Previous studies of feeds of domestic animals have shown that smaller digesta particle size leads to more efficient digestion. Increased digesta particle size—either due to animal factors (e.g., a senile dentition) or to feed factors (e.g., fracture resistance) could be a sign of an animal experiencing compromised nutritional intake. However, for some primates that are dietary generalists, digesta particle size has been shown to increase when consuming preferred foods, which raises doubts about the role of chewing in digesting such foods. This uncertainty makes it difficult to understand the connection between diet, chewing, and digestion through digesta particle size in dietary generalists. In this study, using five typical food items from the Japanese macaque (Macaca fuscata) diet, we conducted in vitro digestibility and fermentation assays to explore the effects of particle size on enzymatic and microbial digestion. For the fermentation assays, we used feces from captive Japanese macaques as inoculum. Among the five food items, we found that particle size has a stronger influence on the digestibility of seeds and mature leaves compared to young leaves and pulp. The influence of particle size on the fermentation rate was stronger in pulp and seeds compared to that in leaves. The differences in physical structure, texture, digestion barriers, and soluble components may play important roles in such differences. These results support the hypothesis that reducing food particle size is less important for consuming fruits than for consuming leaves. The limited effects of particle size on digesting fruits suggest that the two fruits examined in this study are cost‐effective concerning food processing and chewing.
Synthesis of Bioctacene‐Incorporated Nanographene with Near‐Infrared Chiroptical Properties
Authors: Xu Xiushang , Muñoz‐Mármol Rafael , Vasylevskyi Serhii , Villa Andrea , Folpini Giulia , Scotognella Francesco , Maria Paternò Giuseppe , Narita Akimitsu
Published: February 2023

We report the synthesis of a hexabenzoperihexacene (HBPH) with two incorporated octacene substructures, which was unambiguously characterized by single‐crystal X‐ray analysis. The theoretical isomerization barrier of the (P,P)‐/(P,M)‐forms was estimated to be 38.4 kcal mol−1, and resolution was achieved by chiral HPLC. Notably, the enantiomers exhibited opposite circular dichroism responses up to the near‐infrared (NIR) region (830 nm) with a high gabs value of 0.017 at 616 nm. Moreover, HBPH demonstrated NIR emission with a maximum at 798 nm and an absolute PLQY of 41 %. The excited‐state photophysical properties of HBPH were investigated by ultrafast transient absorption spectroscopy, revealing an intriguing feature that was attributed to the rotational and/or conformational dynamics of HBPH after excitation. These results provide new insight into the design of chiral nanographene with NIR optical properties for potential chiroptical applications.
Supramolekulare Kapselkatalyse ermöglicht die Erforschung des von der Natur unerschlossenen chemischen Raums der Terpenoide
Authors: Némethová Ivana , Schmid Dario , Tiefenbacher Konrad
Published: February 2023

Terpene stellen die größte und vielfältigste Klasse von Naturstoffen dar. Dies ist bemerkenswert, da die gesamte Vielfalt aus nur einer Handvoll hoch konservierter linearer Vorstufen zugänglich ist. Eine Modifizierung der Zyklisierungsvorstufen würde eine dramatische Erweiterung des zugänglichen chemischen Raums ermöglichen. Natürliche Enzyme ermöglichen es uns jedoch nicht, dieses Potenzial zu nutzen, da sie keine größeren Abweichungen von der prototypischen Substratstruktur tolerieren. Hier berichten wir, dass die supramolekulare Kapselkatalyse einen einfachen Zugang zu verschiedenen und neuartigen Terpenoidgerüsten ermöglicht, die formal auf C3‐Phenyl‐, Benzyl‐ und Homoprenylderivate von Farnesol zurückgeführt werden können. Neuartige Gerüste, die mit der Presilphiperfolan‐Kernstruktur verwandt sind, sowie neuartige Neoclovenderivate wurden in nur vier Syntheseschritten effizient zugänglich gemacht. Wichtig ist, dass die erhaltenen Produkte funktionelle Gruppen tragen, die leicht weiter derivatisiert werden können. Die erzielten Ergebnisse zeigen das Potenzial der supramolekularen Katalyse für die Erschließung des riesigen chemischen Raums der Terpenoide, der von der Natur noch nicht genutzt wurde.
Integrating Computation, Experiment, and Machine Learning in the Design of Peptide‐Based Supramolecular Materials and Systems
Authors: Ramakrishnan Maithreyi , van Teijlingen Alexander , Tuttle Tell , Ulijn R. V.
Published: February 2023

Interest in peptide‐based supramolecular materials has grown extensively since the 1980s and the application of computational methods has paralleled this. These methods contribute to the understanding of experimental observations based on interactions and inform the design of new supramolecular systems. They are also used to virtually screen and navigate these very large design spaces. Increasingly, the use of artificial intelligence is employed to screen far more candidates than traditional methods. Based on a brief history of computational and experimentally integrated investigations of peptide structures, we explore recent impactful examples of computationally driven investigation into peptide self‐assembly, focusing on recent advances in methodology development. It is clear that the integration between experiment and computation to understand and design new systems is becoming near seamless in this growing field.
An Amphiphilic Molecule‐Regulated Core‐Shell‐Solvation Electrolyte for Li‐Metal Batteries at Ultra‐Low Temperature
Authors: Shi Junkai , Xu Chao , Lai Jiawei , Li Zhongliang , Zhang Yuping , Liu Yan , Ding Kui , Cai Yue‐Peng , Shang Rui , Zheng Qifeng
Published: February 2023

Lithium metal batteries hold great promise for promoting energy density and operating at low temperatures, yet they still suffer from insufficient Li compatibility and slow kinetic, especially at ultra‐low temperatures. Herein, we rationally design and synthesize a new amphiphilic solvent, 1,1,2,2‐tetrafluoro‐3‐methoxypropane, for use in battery electrolytes. The lithiophilic segment is readily to solvate Li+to induce self‐assembly of the electrolyte solution to form a peculiar core‐shell‐solvation structure. Such unique solvation structure not only largely improves the ionic conductivity to allow fast Li+transport and lower the desolvation energy to enable facile desolvation, but also leads to the formation of a highly robust and conductive inorganic SEI. The resulting electrolyte demonstrates high Li efficiency and superior cycling stability from room temperature to −40 °C at high current densities. Meanwhile, anode‐free high‐voltage cell retains 87 % capacity after 100 cycles.
Total Biosynthesis of Mutaxanthene Unveils a Flavoprotein Monooxygenase Catalyzing Xanthene Ring Formation
Authors: Xiang Lang , Shi Jing , Zhu Ao , Xu Zi Fei , Liu Shuang He , Wang Yi Shuang , Guo Zhi Kai , Jiao Rui Hua , Tan Ren Xiang , Ge Hui Ming
Published: February 2023

Flavoprotein monooxygenases (FPMOs) play important roles in generating structural complexity and diversity in natural products biosynthesized by type II polyketide synthases (PKSs). In this study, we used genome mining to discover novel mutaxanthene analogues and investigated the biosynthesis of these aromatic polyketides and their unusual xanthene framework. We determined the complete biosynthetic pathway of mutaxathene through in vivo gene deletion and in vitro biochemical experiments. We show that a multifunctional FPMO, MtxO4, catalyzes ring rearrangement and generates the required xanthene ring through a multistep transformation. In addition, we successfully obtained all necessary enzymes for in vitro reconstitution and completed the total biosynthesis of mutaxanthene in a stepwise manner. Our results revealed the formation of a rare xanthene ring in type II polyketide biosynthesis, and demonstrate the potential of using total biosynthesis for the discovery of natural products synthesized by type II PKSs.
Tetranuclear CuIICluster as the Ten Node Building Unit for the Construction of a Metal–Organic Framework for Efficient C2H2/CO2Separation
Authors: Xiang Fahui , Zhang Hao , Yang Yisi , Li Lu , Que Zhenni , Chen Liangji , Yuan Zhen , Chen Shimin , Yao Zizhu , Fu Jianwei , Xiang Shengchang , Chen Banglin , Zhang Zhangjing
Published: February 2023

Rational design of high nuclear copper cluster‐based metal–organic frameworks has not been established yet. Herein, we report a novel MOF (FJU‐112) with the ten‐connected tetranuclear copper cluster [Cu4(PO3)2(μ2‐H2O)2(CO2)4] as the node which was capped by the deprotonated organic ligand of H4L (3,5‐Dicarboxyphenylphosphonic acid). With BPE (1,2‐Bis(4‐pyridyl)ethane) as the pore partitioner, the pore spaces in the structure ofFJU‐112were divided into several smaller cages and smaller windows for efficient gas adsorption and separation.FJU‐112exhibits a high separation performance for the C2H2/CO2separation, which were established by the temperature‐dependent sorption isotherms and further confirmed by the lab‐scale dynamic breakthrough experiments. The grand canonical Monte Carlo simulations (GCMC) studies show that its high C2H2/CO2separation performance is contributed to the strong π‐complexation interactions between the C2H2molecules and framework pore surfaces, leading to its more C2H2uptakes over CO2molecules.
Comparative Characterization of Diverse DNA Aptamers for Recognition of Spike Proteins of Multiple SARS‐CoV‐2 Variants
Authors: Zhang Zijie , Li Jiuxing , Amini Ryan , Mansfield Alexandria , Gu Jimmy , Xia Jianrun , Brennan John D. , Li Yingfu
Published: February 2023

Many DNA aptamers have been reported to target the spike protein (S‐protein) of SARS‐CoV‐2. These aptamers display different affinities or recognize different epitopes of the S‐protein. We conducted a comparative study of 9 DNA aptamers for binding to several variants of the S‐protein and pseudoviruses using the same testing methods, including dot‐blot assays and enzyme‐linked aptamer binding assays, to evaluate their affinity ranking and analytical utility. Moreover, the binding sites of these aptamers on the S‐protein were examined using aptamer competition assays to understand the effect of S‐protein mutations on aptamer affinity and the degree of overlapping of the binding sites by these aptamers.
Tropical mesoscale convective system formation environments
Authors: Galarneau Thomas J. , Zeng Xubin , Dixon Ross D. , Ouyed Amir , Su Hui , Cui Wenjun
Published: February 2023

Mesoscale convective systems (MCSs) in the tropics play an integral role in the water cycle, are associated with local hazardous weather conditions, and have significant remote impacts on the midlatitude jet stream. Although it is known that MCSs occur in relatively moist environments, it is unclear how far in advance favorable ingredients (lift, instability, and moisture) in the mesoscale environment precede MCS formation. In this study, an automated MCS tracking algorithm and global reanalyses are used to examine the pre‐MCS environment for 3295 MCSs that occurred in the tropics in a 3‐month period. Results showed that increased water vapor and mesoscale ascent implied by low‐level convergence and upper‐level divergence preceded MCS formation by up to 24 h. Regional variations in pre‐MCS environment conditions were apparent and are discussed. Future work will study to what extent these moisture and wind anomalies can be used to predict MCS formation.
Structure and stability of differentially rotating compact stellar objects
Authors: Farrell Delaney , Negreiros Rodrigo , Weber Fridolin
Published: February 2023

Depending on the dynamics of a binary neutron star merger, the collision may result in a differentially rotating compact object. Differentially rotating stars can sustain a total mass considerably higher than that of a uniformly rotating star, giving rise to “hypermassive” objects like hypermassive neutron stars. These stars are likely to exhibit extreme structural deformation along the radial axis due to their high masses. Both the increased mass and structural deformations supported by differential rotation allow the compact remnant to remain stable in otherwise unstable configurations on short, dynamical timescales. In this work, we numerically simulate differentially rotating neutron stars to explore an increase in mass and structural deformation for three relativistic mean‐field equations of state models. Results are used to predict outcomes for recent gravitational wave observations of binary neutron star mergers.
Seasonality of main childhood embryonal tumours and rhabdomyosarcoma, France, 2000–2015
Authors: Awounou Danielle , Lacour Brigitte , Desandes Emmanuel , Guissou Sandra , Cassoux Nathalie , Doz François , Dufour Christelle , Minard‐Colin Véronique , Schleiermacher Gudrun , Taque Sophie , Verschuur Arnauld , Clavel Jacqueline , Goujon Stéphanie
Published: February 2023

Few studies have investigated the seasonal patterns of embryonal tumours. Based on data from the French National Registry of Childhood Cancers, the present study aimed to investigate seasonal variations in embryonal tumour incidence rates by month of birth and by month of diagnosis. The study included 6635 primary embryonal tumour cases diagnosed before the age of 15 years over the period 2000‐2015 in mainland France. Assuming monthly variations in incidence rates were homogeneous over 2000‐2015, we used a Poisson regression model to test for overall heterogeneity in standardised incidence ratios (SIRs) by month of birth or diagnosis. The seasonal scan statistic method was used to detect monthly excesses or deficits of embryonal tumour cases over the whole study period. The annual reproducibility of the observed monthly variations was formally tested. An overall heterogeneity in incidence rates by month of birth was observed for rhabdomyosarcoma in boys only. Based on the month of diagnosis, a seasonality was evidenced for unilateral retinoblastoma, with a lower incidence rate in the summer (SIRJul‐Aug = 0.68, 95% CI = 0.52‐0.87), whilst the incidence rate of rhabdomyosarcoma tended to be lower in August (SIRAug = 0.68, 95% CI = 0.52‐0.89). No seasonality was detected for the other embryonal tumour groups by month of birth or month of diagnosis. This study is one of the largest to have investigated the seasonality of childhood embryonal tumours. The study showed a seasonal variation in the incidence rates by month of diagnosis for unilateral retinoblastoma and rhabdomyosarcoma. Our findings are likely to reflect a delay in consultation during the summer months. However, the role of seasonally varying environmental exposures cannot be ruled out.