bluuebunny/crossref_metadata_2025 huggingface dataset:
The structure of accreted stellar streams
Authors: Qian Yansong , Arshad Yumna , Bovy Jo
Published: January 2022

Many of the Milky Way’s globular clusters are likely accreted from satellite galaxies that have long since merged with the Milky Way. When these globular clusters are susceptible to tidal disruption, this process likely starts already inside the parent satellite leading to an early stellar stream within the satellite. When the parent satellite merges with the Milky Way, the globular cluster and its pre-merger stellar stream are accreted in a somewhat chaotic process. Here, we investigate the properties of the accreted stream after the merger as we would see it today using a suite of simulations of accretion events. We find that the accretion process leads to a wide range of behaviours, but generally scatters the accreted stream over a wide, 2D area of the sky. The behaviour ranges from a set of a few or more well-defined ‘sub-streams’ extending out from the post-merger thin stream by tens of degrees to more widely dispersed debris over much of the sky, depending on how close to the centre of the Milky Way the merger happened. Using mock Gaia-like observations of the simulated streams, we demonstrate that an accreted-stream component can explain the off-track features observed in the GD-1 stream. Sub-streams can appear like thin tidal streams themselves that are seemingly unassociated with the post-merger stream, raising the possibility that some of the progenitor-less streams observed in the Milky Way are part of a single or a few accreted streams created in an ancient merger event.
Eccentricity evolution of massive black hole binaries from formation to coalescence
Authors: Gualandris Alessia , Khan Fazeel Mahmood , Bortolas Elisa , Bonetti Matteo , Sesana Alberto , Berczik Peter , Holley-Bockelmann Kelly
Published: January 2022

Coalescing supermassive black hole binaries (BHBs) are expected to be the loudest sources of gravitational waves (GWs) in the Universe. Detection rates for ground or space-based detectors based on cosmological simulations and semi-analytic models are highly uncertain. A major difficulty stems from the necessity to model the BHB from the scale of the merger to that of inspiral. Of particular relevance to the GW merger time-scale is the binary eccentricity. Here, we present a self-consistent numerical study of the eccentricity of BHBs formed in massive gas-free mergers from the early stages of the merger to the hardening phase, followed by a semi-analytical model down to coalescence. We find that the early eccentricity of the unbound black hole pair is largely determined by the initial orbit. It systematically decreases during the dynamical friction phase. The eccentricity at binary formation is affected by stochasticity and noise owing to encounters with stars, but preserves a strong correlation with the initial orbital eccentricity. Binding of the black holes is a phase characterized by strong perturbations; and we present a quantitative definition of the time of binary formation. During hardening the eccentricity increases in minor mergers, unless the binary is approximately circular, but remains largely unchanged in major mergers, in agreement with predictions from semi-analytical models based on isotropic scattering experiments. Coalescence times due to hardening and GW emission in gas-poor non-rotating ellipticals are ≲ 0.5 Gyr for the large initial eccentricities (0.5 ≤ e ≤ 0.9) typical of galaxy mergers in cosmological simulations.
The cycle of metals in the infalling elliptical galaxy NGC 1404
Authors: Mernier F , Werner N , Su Y , Pinto C , Grossová R , Simionescu A , Iodice E , Sarzi M , Görgei A
Published: January 2022

Hot atmospheres pervading galaxy clusters, groups, and early-type galaxies are rich in metals, produced during epochs and diffused via processes that are still to be determined. While this enrichment has been routinely investigated in clusters, metals in lower mass systems are more challenging to probe with standard X-ray exposures and spectroscopy. In this paper, we focus on very deep XMM–Newton (∼350 ks) observations of NGC 1404, a massive elliptical galaxy experiencing ram-pressure stripping of its hot atmosphere while infalling towards the centre of the Fornax cluster, with the aim to derive abundances through its hot gas extent. Importantly, we report the existence of a new fitting bias – the ‘double Fe bias’ – leading to an underestimate of the Fe abundance when two thermal components cannot realistically model the complex temperature structure present in the outer atmosphere of the galaxy. Contrasting with the ‘metal conundrum’ seen in clusters, the Fe and Mg masses of NGC 1404 are measured 1–2 orders of magnitude below what stars and supernovae could have reasonably produced and released. In addition, we note the remarkable Solar abundance ratios of the galaxy’s halo, different from its stellar counterpart but similar to the chemical composition of the ICM of rich clusters. Completing the clusters regime, all these findings provide additional support towards a scenario of early enrichment, at play over two orders of magnitude in mass. A few peculiar and intriguing features, such as a possible double metal peak as well as an apparent ring of enhanced Si near the galaxy core, are also discussed.
Effect of evolving physical constants on type Ia supernova luminosity
Authors: Gupta Rajendra P
Published: January 2022

Type Ia supernovae, SNeIa, are used as standard candles in cosmology to determine the distances of the galaxies harbouring them. We show that the luminosity of an SNIa depends on its distance from us when physical constants (the speed of light c, the gravitational constant G, and the Planck constant h) are permitted to evolve. It is because the Chandrasekhar mass of the white dwarf that explodes to create SNIa depends on the values of the constants at the epoch the SNIa is formed. We show that the SNeIa luminosities could be about four times higher in the past than they are now. Thus, the luminosity distance estimation of the earliest SNeIa could be off by up to a factor of 2. Cosmological parameters, determined with this correction applied to the redshift versus distance modulus data base (Pantheon SNeIa), are not very different from those from the standard ΛCDM model without this correction, except for the dark-energy density and the curvature energy density; the latter increases at the cost of the former. Variations of the constants are given by $\dot{G}/G = \ 3.90 \ ( { \pm 0.04} ) \times {10^{ - 10}}\ {\rm y{r^{ - 1}}}$and $\dot{c}/c = \dot{h}/h\ = \ 1.30\ ( { \pm 0.01} ) \times {10^{ - 10}}\ {\rm y{r^{ - 1}}}$ at present. These variations are valid only when $G,\ c,\ $and$\ h$ are permitted to vary concurrently rather than individually.
Evolutionary rewiring of regulatory networks contributes to phenotypic differences between human and mouse orthologous genes
Authors: Ha Doyeon , Kim Donghyo , Kim Inhae , Oh Youngchul , Kong JungHo , Han Seong Kyu , Kim Sanguk
Published: January 2022

Mouse models have been engineered to reveal the biological mechanisms of human diseases based on an assumption. The assumption is that orthologous genes underlie conserved phenotypes across species. However, genetically modified mouse orthologs of human genes do not often recapitulate human disease phenotypes which might be due to the molecular evolution of phenotypic differences across species from the time of the last common ancestor. Here, we systematically investigated the evolutionary divergence of regulatory relationships between transcription factors (TFs) and target genes in functional modules, and found that the rewiring of gene regulatory networks (GRNs) contributes to the phenotypic discrepancies that occur between humans and mice. We confirmed that the rewired regulatory networks of orthologous genes contain a higher proportion of species-specific regulatory elements. Additionally, we verified that the divergence of target gene expression levels, which was triggered by network rewiring, could lead to phenotypic differences. Taken together, a careful consideration of evolutionary divergence in regulatory networks could be a novel strategy to understand the failure or success of mouse models to mimic human diseases. To help interpret mouse phenotypes in human disease studies, we provide quantitative comparisons of gene expression profiles on our website (http://sbi.postech.ac.kr/w/RN).
Usage of the H3 variants during the S-phase of the cell cycle in Physarum polycephalum
Authors: Thiriet Christophe
Published: January 2022

DNA replication occurring in S-phase is critical for the maintenance of the cell fate from one generation to the next, and requires the duplication of epigenetic information. The integrity of the epigenome is, in part, insured by the recycling of parental histones and de novo deposition of newly synthesized histones. While the histone variants have revealed important functions in epigenetic regulations, the deposition in chromatin during S-phase of newly synthesized histone variants remains unclear. The identification of histone variants of H3 and unique features of Physarum polycephalum provides a powerful system for investigating de novo deposition of newly synthesized histones by tracking the incorporation of exogenous histones within cells. The analyses revealed that the rate of deposition of H3.1 and H3.3 is anticorrelated as S-phase progresses, H3.3 is predominately produced and utilized in early S and dropped throughout S-phase, while H3.1 behaved in the opposite way. Disturbing the expression of H3 variants by siRNAs revealed mutual compensation of histone transcripts. Interestingly, the incorporation of pre-formed constrained histone complexes showed that tetramers of H3/H4 are more efficiently utilized by the cell than dimers. These results support the model whereby the histone variant distribution is established upon replication and new histone deposition.
High mobility group AT-hook 1 (HMGA1) is an important positive regulator of hepatitis B virus (HBV) that is reciprocally upregulated by HBV X protein
Authors: Shen Zhongliang , Wu Jingwen , Gao Zixiang , Zhang Shenyan , Chen Jingwen , He Jingjing , Guo Yifei , Deng Qiang , Xie Youhua , Liu Jing , Zhang Jiming
Published: January 2022

Chronic infection with hepatitis B virus (HBV) is associated with liver cirrhosis and hepatocellular carcinoma. Upon infection of hepatocytes, HBV covalently closed circular DNA (cccDNA) exists as histone-bound mini-chromosome, subjected to transcriptional regulation similar to chromosomal DNA. Here we identify high mobility group AT-hook 1 (HMGA1) protein as a positive regulator of HBV transcription that binds to a conserved ATTGG site within enhancer II/core promoter (EII/Cp) and recruits transcription factors FOXO3α and PGC1α. HMGA1-mediated upregulation of EII/Cp results in enhanced viral gene expression and genome replication. Notably, expression of endogenous HMGA1 was also demonstrated to be upregulated by HBV, which involves HBV X protein (HBx) interacting with SP1 transcription factor to activate HMGA1 promoter. Consistent with these in vitro results, chronic hepatitis B patients in immune tolerant phase display both higher intrahepatic HMGA1 protein levels and higher serum HBV markers compared to patients in inactive carrier phase. Finally, using a mouse model of HBV persistence, we show that targeting endogenous HMGA1 through RNA interference facilitated HBV clearance. These data establish HMGA1 as an important positive regulator of HBV that is reciprocally upregulated by HBV via HBx and also suggest the HMGA1-HBV positive feedback loop as a potential therapeutic target.
Structural characterization of the ANTAR antiterminator domain bound to RNA
Authors: Walshe James L , Siddiquee Rezwan , Patel Karishma , Ataide Sandro F
Published: January 2022

Regulated transcription termination provides an efficient and responsive means to control gene expression. In bacteria, rho-independent termination occurs through the formation of an intrinsic RNA terminator loop, which disrupts the RNA polymerase elongation complex, resulting in its dissociation from the DNA template. Bacteria have a number of pathways for overriding termination, one of which is the formation of mutually exclusive RNA motifs. ANTAR domains are a class of antiterminator that bind and stabilize dual hexaloop RNA motifs within the nascent RNA chain to prevent terminator loop formation. We have determined the structures of the dimeric ANTAR domain protein EutV, from Enterococcus faecialis, in the absence of and in complex with the dual hexaloop RNA target. The structures illustrate conformational changes that occur upon RNA binding and reveal that the molecular interactions between the ANTAR domains and RNA are restricted to a single hexaloop of the motif. An ANTAR domain dimer must contact each hexaloop of the dual hexaloop motif individually to prevent termination in eubacteria. Our findings thereby redefine the minimal ANTAR domain binding motif to a single hexaloop and revise the current model for ANTAR-mediated antitermination. These insights will inform and facilitate the discovery of novel ANTAR domain RNA targets.
Nicotine Patch Alters Patterns of Cigarette Smoking-Induced Dopamine Release: Patterns Relate to Biomarkers Associated With Treatment Response
Authors: Zakiniaeiz Yasmin , Liu Heather , Gao Hong , Najafzadeh Soheila , Ropchan Jim , Nabulsi Nabeel , Huang Yiyun , Matuskey David , Chen Ming-Kai , Cosgrove Kelly P , Morris Evan D
Published: January 2022

Introduction

Tobacco smoking is a major public health burden. The first-line pharmacological treatment for tobacco smoking is nicotine replacement therapy (eg, the nicotine patch (NIC)). Nicotine acts on nicotinic-acetylcholine receptors on dopamine terminals to release dopamine in the ventral and dorsal striatum encoding reward and habit formation, respectively.

Aims and Methods

To better understand treatment efficacy, a naturalistic experimental design combined with a kinetic model designed to characterize smoking-induced dopamine release in vivo was used. Thirty-five tobacco smokers (16 female) wore a NIC (21 mg, daily) for 1-week and a placebo patch (PBO) for 1-week in a randomized, counter-balanced order. Following 1-week under NIC and then overnight abstinence, smokers participated in a 90-minute [11C]raclopride positron emission tomography scan and smoked a cigarette while in the scanner. Identical procedures were followed for the PBO scan. A time-varying kinetic model was used at the voxel level to model transient dopamine release peaking instantaneously at the start of the stimulus and decaying exponentially. Magnitude and spatial extent of dopamine release were estimated. Smokers were subcategorized by nicotine dependence level and nicotine metabolism rate.

Results

Dopamine release magnitude was enhanced by NIC in ventral striatum and diminished by NIC in dorsal striatum. More-dependent smokers activated more voxels than the less-dependent smokers under both conditions. Under PBO, fast metabolizers activated more voxels in ventral striatum and fewer voxels in dorsal striatum compared to slow metabolizers.

Conclusions

These findings demonstrate that the model captured a pattern of transient dopamine responses to cigarette smoking which may be different across smoker subgroup categorizations.

Implications

This is the first study to show that NIC alters highly localized patterns of cigarette smoking-induced dopamine release and that levels of nicotine dependence and nicotine clearance rate contribute to these alterations. This current work included a homogeneous subject sample with regards to demographic and smoking variables, as well as a highly sensitive model capable of detecting significant acute dopamine transients. The findings of this study add support to the recent identification of biomarkers for predicting the effect of nicotine replacement therapies on dopamine function which could help refine clinical practice for smoking cessation.
Trastuzumab Deruxtecan Improves Progression-Free Survival and Intracranial Response in Patients with HER2-Positive Metastatic Breast Cancer and Brain Metastases
Authors: Jacobson Anne
Published: January 2022

In the phase III DESTINY-Breast03 trial, trastuzumab deruxtecan improved progression-free survival (PFS) relative to trastuzumab emtansine across all patients with HER2-positive metastatic breast cancer, including a 75% improvement in PFS among those with baseline brain metastases.
Pembrolizumab and Trastuzumab in High Tumor Mutational Burden and POLE-Mutated HER2-Positive Refractory Breast Cancer
Authors: Zhang Li , Chen Yimeng , Lv Yao , Jiao Shunchang , Zhao Weihong
Published: January 2022

Metastatic breast cancer (mBC) is an incurable disease, and it is not sensitive to immunotherapy due to its low immunogenicity. Recently, inactivated DNA polymerase epsilon (POLE) mutations have been found to be associated with high tumor mutational burden (TMB), which is an effective immuno-oncology biomarker. Patients with POLE mutations with different types of cancer have properly responded to immunotherapy. We aimed to report the first case of programmed death-ligand 1 (PD-L1)-negative mBC presenting with high TMB and POLE mutations, in which a complete response to 5 cycles of chemotherapy and 1 year of pembrolizumab and trastuzumab was noted after failing several lines of HER2-targeted therapies. Our findings also suggest that biomarker-driven patient selection is highly significant for further clinical development of combination therapies via anti-HER2 plus immune-checkpoint inhibitors for HER2+ BC patients.
Urban Climate Adaptation
Authors: Chu Eric , Shi Linda
Published: January 2022

Despite early optimism in cities’ leadership on climate adaptation planning, critics increasingly find that prevailing adaptation interventions are financially speculative, economically exclusive, and socially discriminatory. In this chapter, the authors discuss how emerging adaptation plans have taken on characteristics of climate urbanism by privileging the epistemologies, operations, and normative values of cities in the Global North, which in turn has shaped the scope, scale, strategies, and empirical evidence of adaptation actions on the ground. Dominant global imaginaries of climate-resilient futures prioritize technological fixes, decentralized and individual responsibility, consumption-led economic growth, and the securitization of upper-middle class values, experiences, and lifestyles. Adaptation planning practice has yet to recognize the long history of alternative epistemologies, everyday strategies, and normative socio-cultural values that tackle the drivers of systemic environmental, racial, and economic injustices in cities. Socio-political instability, even under currently observed warming trends, suggests that effective and just adaptation moving forward must be more political, relational, and anticipatory not only to biophysical changes but also to responses from the market, state, community, and social movements. Adaptation plans must therefore engage with epistemologies heretofore sidelined in the field, including critical political economy, embodied knowledge, postcolonial, anti-racist, and feminist studies. This chapter charts a way to comparatively view these alternative perspectives from “off the map” that are essential in pursuit of more just, equitable, and sustainable cities.
Illegal Wildlife Trade in the Mekong
Authors: Nillasithanukroh Songkhun , Patel Ekta , Malesky Edmund , Weinthal Erika
Published: January 2022

This chapter examines the illegal wildlife trade (IWT) in the Mekong, with particular attention to how political economic factors and legal structures shape actors’ interests and incentives. The current literature on wildlife trafficking mainly attributes wildlife protection failures to weak enforcement. However, this literature has paid little attention to the underlying factors that contribute to the weak enforcement of wildlife laws. This chapter applies a political economy analysis to better understand the role of each actor from the point of wildlife sourcing to end consumption. It also explains why effectively enforcing wildlife laws is difficult and is often not in the interest of wildlife officials. This chapter thus examines why actors along IWT supply chains engage in illegal activities and do not abide by conservation laws. With rising demand for wildlife products, particularly because of increasing economic prosperity, the survival of many endangered species is under threat. Despite growing calls for total bans of wildlife trade or trade regulations to prevent overharvesting, these frequently fail to achieve conservation goals if they do not consider the local political economy context. This chapter focuses on the global IWT hotspots of Vietnam, Laos, and Cambodia, analyzing how legal frameworks shape local political economies and showing why IWT is a pervasive problem in the region.
US Efforts to Promote Peace in the Nineteenth Century
Authors: Minardi Margot
Published: January 2022

Fueled by both religious and secular ideals, an organized peace movement emerged in the United States in the aftermath of the War of 1812 and the Napoleonic Wars. Rather than protesting a particular war, peace reformers in this period sought to rout out warfare entirely. Some nineteenth-century American advocates of peace promoted alternative forms of conflict resolution, such as a congress of nations or arbitration agreements, to the governments of the world. Others sought to make peace from the bottom up, coupling the pacifist cause with calls for democratization, workers’ rights, and the abolition of slavery. These two approaches, while occasionally intersecting, stemmed from different understandings of the problem of war: was war to be understood primarily as the product of conflict between nation-states, or was it a manifestation of a social system rooted in inequality and inhumanity? The tensions within the movement were particularly evident at key moments in the nineteenth century, including the rise of abolitionism in the 1830s, the midcentury international peace congresses in Europe, and the period outbreak of war (particularly the Civil War within the United States). This chapter argues that debates over the relationship between peace and social reform permeated nineteenth-century American advocacy for peace, as peace reformers grappled with explaining how social and political transformation could happen in the absence of war.
Analysis of exocyst function in endodermis reveals its widespread contribution and specificity of action
Authors: Hématy Kian , De Bellis Damien , Wang Xin , Mähönen Ari Pekka , Geldner Niko
Published: January 2022

The exocyst is the main plasma membrane vesicle-tethering complex in eukaryotes and is composed of eight different subunits. Yet, in plant genomes, many subunits display multiple copies, thought to reflect evolution of complex subtypes with divergent functions. In Arabidopsis thaliana root endodermal cells, the isoform EXO70A1 is required for positioning of CASP1 at the Casparian Strip Domain, but not for its non-targeted secretion to the plasma membrane. Here, we show that exo84b resembles exo70a1 mutants regarding CASP1 mistargeting and secretion of apoplastic proteins, but exo84b additionally affects secretion of other integral plasma membrane proteins. Moreover, conditional, cell-type-specific gene editing of the single-copy core component SEC6 allows visualization of secretion defects in plant cells with a complete lack of exocyst complex function. Our approach opens avenues for deciphering the complexity/diversity of exocyst functions in plant cells and enables analysis of central trafficking components with lethal phenotypes.
Consumers’ willingness to pay for pork produced with different levels of antibiotics
Authors: Paudel Bindu , Kolady Deepthi , Grebitus Carola , Roy Aniruddha , Ishaq Mariam
Published: January 2022

Compared with the EU, regulations on antibiotic use in livestock are less stringent in the USA. If consumers prefer non-antibiotic or minimal antibiotic-use meat, labeling different levels of antibiotic use in the USA could have the potential to mitigate the development of antibiotic-resistant livestock. This study used a survey of 660 US consumers to estimate willingness to pay (WTP) for pork chops from pigs raised with different levels of antibiotic use. Results show that WTP for antibiotic-free pork chops is higher compared with WTP for pork chops produced with minimal use of antibiotics for disease treatment and conventional use of antibiotics for growth promotion. These findings suggest that it could be beneficial to differentiate usage levels of antibiotics when labeling pork products rather than stating ‘use’ or ‘no use’.
‘Pericles’, ‘Reynard the Foxe’, Sidney’s ‘Arcadia’, Florio’s ‘Montaigne’ and More in Northwestern MS 67
Authors: Coatalen Guillaume
Published: January 2022

This paper offers an edition of 214 extracts contained in Northwestern MS 67, a manuscript completed no earlier than 1614, and a commentary on the compiler’s choices and practice. His identity is difficult to establish with any certainty but a lengthy letter in Latin by one Hugo Richardes to one William Yong dated 14 December 1583, and written at Basteldon (Basildon), is copied at the end of the commonplace book. The material ranges from playbooks (by Dekker, Marston and Shakespeare) to pastorals (Sidney’s ‘Arcadia’ and Tofte’s ‘Honours Academie’), through extracts from Plutarch’s ‘Lives’ in North’s translation. There are 28 translations of classical verse transcribed from Plutarch. Seven extracts from Montaigne’s ‘Essays’ in Florio’s translation also occur, but the most surprising source is probably Caxton’s 1550 ‘Reynard the Foxe’ which furnishes 50 quotations. In the beginning of the commonplace book, the compiler explains its purpose by using the well-known Senecan bee and honey trope: applying the extracts to discourse and life. All the extracts are adapted and kept in alphabetical order according to the first word of the extract. Most are proverbial in nature or copied to sound like sentences, and all point to an inspiration for moral and spiritual improvement. The extracts express humanistic concerns, like the power of eloquence and the treachery of public life, and Stoic principles such as constancy in the face of adversity. One central issue seems to be remaining virtuous in a sinful world.
Acquiring Innovation under Information Frictions
Authors: Celik Murat Alp , Tian Xu , Wang Wenyu
Published: January 2022

Acquiring innovation through M&A is subject to information frictions, as assessing the value of innovative targets is a challenging task. We find an inverted U-shaped relation between firm innovation and takeover exposure; equity usage increases with target innovation; and the deal completion rate drops with innovation. We develop and estimate a model of acquiring innovation under information frictions, featuring endogenous merger, innovation, and offer composition decisions. Our estimates suggest that acquirers’ due diligence reveals only 30$\%$ of private information possessed by targets. Eliminating information frictions increases capitalized merger gains by 59$\%$, stimulates innovation, and boosts productivity, business dynamism, and social welfare.
Deep learning algorithms for magnetic resonance imaging of inflammatory sacroiliitis in axial spondyloarthritis
Authors: Lin Karina Ying Ying , Peng Cao , Lee Kam Ho , Chan Shirley Chiu Wai , Chung Ho Yin 
Published: January 2022

Objective

The aim of this study was to develop a deep learning algorithm for detection of active inflammatory sacroiliitis in short tau inversion recovery (STIR) sequence MRI.

Methods

A total of 326 participants with axial SpA, and 63 participants with non-specific back pain (NSBP) were recruited. STIR MRI of the SI joints was performed and clinical data were collected. Region of interests (ROIs) were drawn outlining bone marrow oedema, a reliable marker of active inflammation, which formed the ground truth masks from which ‘fake-colour’ images were derived. Both the original and fake-colour images were randomly allocated into either the training and validation dataset or the testing dataset. Attention U-net was used for the development of deep learning algorithms. As a comparison, an independent radiologist and rheumatologist, blinded to the ground truth masks, were tasked with identifying bone marrow oedema in the MRI scans.

Results

Inflammatory sacroiliitis was identified in 1398 MR images from 228 participants. No inflammation was found in 3944 MRI scans from 161 participants. The mean sensitivity of the algorithms derived from the original dataset and fake-colour image dataset were 0.86 (0.02) and 0.90 (0.01), respectively. The mean specificity of the algorithms derived from the original and the fake-colour image datasets were 0.92 (0.02) and 0.93 (0.01), respectively. The mean testing dice coefficients were 0.48 (0.27) for the original dataset and 0.51 (0.25) for the fake-colour image dataset. The area under the curve of the receiver operating characteristic (AUC-ROC) curve of the algorithms using the original dataset and the fake-colour image dataset were 0.92 and 0.96, respectively. The sensitivity and specificity of the algorithms were comparable with the interpretation by a radiologist, but outperformed that of the rheumatologist.

Conclusion

An MRI deep learning algorithm was developed for detection of inflammatory sacroiliitis in axial SpA.
Integration patterns of cheek teeth and ecomorphological evolution in grinding herbivores: the case of caviine rodents (Caviomorpha: Caviidae)
Authors: Boivin Myriam , Álvarez Alicia , Ercoli Marcos D
Published: January 2022

Caviid rodents have peculiar craniomandibular specializations toward masticatory propalinal movements and grinding, in relation to a grass-rich diet. The aim of this study is to: (1) analyse the variation of cheek tooth shape in the Caviinae and, (2) quantify the covariation relations between caviine cheek teeth. For this purpose, we perform the first geometric morphometric analysis on cheek teeth of fossil and extant caviids, ancestral shape reconstructions and covariation analyses. Our results show that caviine dentition is strongly integrated with a higher covariation between teeth of the same row than between opposite teeth, differing from mammals with complex interlocking. Each series acts as a single functional unit integrated during grinding action obtained by mainly propalinal movements. However, p4 shows more plasticity, allowing its morphology to differentiate from the common pattern of molars. Morphologically homogeneous cheek tooth series are ancestral in crown caviids and highly marked in Cavia, while stronger morphological differences between tooth pieces are observed in Microcavia and Galea. These differences are probably driven by diet changes. The tendency towards alignment of main masticatory movements with the tooth row axes seems to be a key factor in understanding cheek tooth covariation patterns in this and other rodent clades.
Hybridizations Between formae speciales of Venturia inaequalis Pave the Way for a New Biocontrol Strategy to Manage Fungal Plant Pathogens
Authors: Caffier Valérie , Shiller Jason , Bellanger Marie-Noëlle , Collemare Jérôme , Expert Pascale , Gladieux Pierre , Pascouau Claire , Sannier Mélanie , Le Cam Bruno
Published: January 2022

Hybridization and adaptation to new hosts are important mechanisms of fungal disease emergence. Evaluating the risk of emergence of hybrids with enhanced virulence is then key to develop sustainable crop disease management. We evaluated this risk in Venturia inaequalis, the fungus responsible for the common and serious scab disease on Rosaceae hosts, including apple, pyracantha, and loquat. Field isolates from these three hosts and progenies obtained from five crosses between formae speciales isolates collected from pyracantha (f. sp. pyracantha) and apple (f. sp. pomi) were tested for their pathogenicity on the three hosts. We confirmed a strict host specificity between isolates from apple and pyracantha and showed that most isolates were able to cause disease on loquat. None of the 251 progeny obtained from five crosses between V. inaequalis f. sp. pyracantha and V. inaequalis f. sp. pomi could infect apple. If confirmed on more crosses, the inability of the hybrids to infect apple could lead to a novel biocontrol strategy based on a sexual hijacking of V. inaequalis f. sp. pomi by a massive introduction of V. inaequalis f. sp. pyracantha in apple orchards. This strategy, analogous to the sterile insect approach, could lead to the collapse of the population size of V. inaequalis and dramatically reduce the use of chemicals in orchards.
Rapidly Increasing Boscalid Resistance in Corynespora cassiicola in China
Authors: Sun Bingxue , Zhu Guangxue , Xie Xuewen , Chai Ali , Li Lei , Fan Tengfei , Li Baoju , Yanxia Shi
Published: January 2022

Corynespora leaf spot caused by Corynespora cassiicola is an important foliar disease in cucumber. Succinate dehydrogenase inhibitors are the main fungicides used to control this disease. With the application of succinate dehydrogenase inhibitors (SDHIs) in the field, boscalid-resistant isolates have been continuously detected in the field. Resistance monitoring programs were performed to investigate the frequency and genotypes of resistant isolates. In our resistance monitoring, the frequency of resistant isolates rapidly increased from 9.68 to 85.88% in 2005 to 2020. Nine genotypes conferring SDHI resistance were found in resistant isolates, with different levels of resistance to SDHIs: B-H278R, B-H278L, B-H278Y, B-I280V, C-N75S, C-S73P, D-D95E, D-H105R, and D-G109V. The first sdh mutation was detected in Hebei Province in China, conferring an amino acid substitution at codon 278 in the sdhB subunit from histidine to tyrosine (B-H278Y), and it was the dominant resistance genotype in 2014 to 2015. Subsequently, other genotypes were gradually detected in the field, and the dominant mutations varied across years and across regions. The newest genotype (B-H278L) conferring SDHI resistance was found in 2020. To the best of our knowledge, this is the first report of C. cassiicola in cucumber. To date, multiple resistance to SDHIs, quinone outside inhibitors, benzimidazole fungicides, and dicarboximide fungicides have been detected, accounting for 75.64% of SDHI-resistant isolates. Therefore, the above four fungicides must be strictly restricted, and further monitoring work in other provinces with more isolates should be performed in the future.
Focus on function
Authors: Sater Pamela Ann Melvin
Published: January 2022

Attention-deficit/hyperactivity disorder (ADHD) is a common disorder affecting people of all ages, and is characterized by inattention, hyperactivity, and impulsivity. Adults frequently have less hyperactivity or impulsivity but struggle more with inattentiveness and restlessness. Adults also may have comorbid psychiatric conditions and substance use issues that can make ADHD challenging to detect and treat. If left untreated, ADHD may harm the patient's quality of life. This article examines therapies for treating adults with ADHD.
Cervical artery dissection
Authors: Nicolas Yunius K. San
Published: January 2022

Cervical artery dissection is a common cause of stroke in young adults and can lead to significant disability. Clinicians should be able to recognize the clinical presentation and diagnose this condition to prevent cerebral ischemia and its complications. Consider cervical artery dissection in a young adult with new-onset, unilateral head pain with or without neck pain with antecedent neck trauma, with or without neurologic deficits or risk factors for dissection. Early diagnosis can lead to better outcomes but the overall prognosis is good for young adults with cervical artery dissection.
Modernizing regulations for treating opioid use disorder during the COVID-19 pandemic
Authors: Iacono Tara M.
Published: January 2022

The opioid epidemic has been the most significant public health crisis in the United States during the past 30 years. In 2021, it was second only to COVID-19. What happens when two epidemics collide and what should policy makers do about it? This article analyzes the burden of COVID-19 on patients with opioid addiction and discusses the beneficial policy changes that improve access to substance abuse care.
Oculomotor and Perceptual Measures of Visual Motion Sensitivity in Patients With Chronic Dizziness Symptoms
Authors: Zaleski-King Ashley , Pinto Robin , Tamaki Chizuko , Bogle Jamie , McCaslin Devin , Brungart Douglas
Published: January 2022

Objective:

The purpose of this study was to provide empirical data describing the relationship between behavioral responses to dynamic visual motion in adults with chronic dizziness symptoms with and without clinically identifiable peripheral vestibular impairment.

Design:

Prospective, quasi-experimental study including individuals with chronic dizziness symptoms with identified unilateral peripheral vestibular impairment (n=27), and individuals with chronic dizziness symptoms without identified vestibular impairment (n=26). We measured (a) visual perception of verticality in a dynamic background, (b) postural displacement in a dynamic background, (c) eye movement behaviors in various visual contexts, and (d) self-rating degree of anxiety.

Results:

Status of peripheral vestibular function was not a significant predictor of behavioral responses to visual motion. The data show that the ability to fixate on a visual target was predictive of postural control in a dynamic visual background. Trial-to-trial variability in verticality responses and degree of self-rated anxiety were also associated with postural control.

Conclusions:

Apart from vestibular function, oculomotor control is important for maintaining control of whole-body motor responses during exposure to a dynamic visual stimulus. Vertical perception precision—not accuracy—may be more important for understanding real-world consequences of visual motion sensitivity. Traditional diagnostic evaluations focusing exclusively on characterizing the peripheral vestibular system may not provide insight into the behaviors associated with visual motion sensitivity.
Mature plasmacytoid dendritic cells associated with acute myeloid leukemia show similar genetic mutations and expression profiles to leukemia cells
Authors: Gong Xiaoyuan , Li Chunhong , Wang Ying , Rao Qing , Mi Yingchang , Wang Min , Wei Hui , Wang Jianxiang
Published: January 2022

Introduction:

Mature plasmacytoid dendritic cells (pDCs) proliferation associated with myeloid neoplasms (MPDMN) are recognized as a neoplasm related to fully differentiated pDCs. Although it has been reported for many years, the genomic landscape of MPDMN is poorly understood.

Methods:

We reported two patients who developed acute myeloid leukemia (French-American-British M5 subtype) coexisted with immunophenotypically mature pDCs proliferation, which fit the diagnosis of MPDMN. We sorted pDCs from myeloid blasts by flow cytometry and performed whole-exome sequencing and RNA sequencing of the two cell populations, respectively.

Results:

The immunophenotypes of pDCs in both patients were positive for CD123bri, HLA-DR, CD4, CD303, CD304, and negative for CD56, CD34, CD117, and TdT. The variant allele frequency of gene mutations in myeloid blasts and pDCs were similar. The expression data showed myeloid blasts clustered tightly with hematopoietic stem cells, and pDCs from patients clustered tightly with granulocyte-monocyte progenitors/common myeloid progenitor, rather than with pDCs from the GEO platform.

Conclusion:

Our study suggested that pDCs derived from the leukemic clone, evidenced by a shared mutation profile and similar transcriptional signatures between pDCs and concurrent myeloid blasts.
Chemosaturation with percutaneous hepatic perfusion of melphalan for metastatic uveal melanoma
Authors: Modi Sachin , Gibson Tom , Vigneswaran Ganesh , Patel Shian , Wheater Matthew , Karydis Ioannis , Gupta Sanjay , Takhar Arjun , Pearce Neil , Ottensmeier Christian , Stedman Brian
Published: January 2022

Uveal melanoma, the most common primary ocular malignancy in adults, carries a poor prognosis: 50% of patients develop the metastatic disease with a 10–25% 1-year survival and no established standard of care treatment. Prior studies of melphalan percutaneous hepatic perfusion (M-PHP) have shown promise in metastatic uveal melanoma (mUM) patients with liver predominant disease but are limited by small sample sizes. We contribute our findings on the safety and efficacy of the procedure in the largest sample population to date. A retrospective analysis of outcome and safety data for all mUM patients receiving M-PHP was performed. Tumour response and treatment toxicity were evaluated using RECIST 1.1 and Common Terminology Criteria for Adverse Events v5.03, respectively. 250 M-PHP procedures were performed in 81 patients (median of three per patient). The analysis demonstrated a hepatic disease control rate of 88.9% (72/81), a hepatic response rate of 66.7% (54/81), and an overall response rate of 60.5% (49/81). After a median follow-up of 12.9 months, median overall progression-free (PFS) and median overall survival (OS) were 8.4 and 14.9 months, respectively. There were no fatal treatment-related adverse events (TRAE). Forty-three grade 3 (29) or 4 (14) TRAE occurred in 23 (27.7%) patients with a significant reduction in such events between procedures performed in 2016–2020 vs. 2012–2016 (0.17 vs. 0.90 per patient, P < 0.001). M-PHP provides excellent response rates and PFS compared with other available treatments, with decreasing side effect profile with experience. Combination therapy with systemic agents may be viable to further advance OS.
Chimeric LSMAP Double-barrel Fibula Free Flap: Goal-oriented Surgical Technique and Tips for One-stage Mandibular Reconstruction
Authors: Massarelli Olindo
Published: January 2022

Composite oromandibular defects involving jaw bones, intraoral and skin/soft tissues, or dynamic structures such as the tongue, soft palate, and pharynx are real reconstructive challenges even today. Despite improvements in oral dental rehabilitation, another complex task to deal with in young patients with dentate or nonatrophic mandible is correcting a too large vertical occlusal dimension, which makes the prosthodontic rehabilitation very challenging. Instead of using more complex and time-consuming methods such as simultaneous free flaps and to avoid further bone graft and second-stage revision procedures, an innovative double-barrel shaped chimeric fibula free flap with lateral supramalleolar artery perforator flap is used to fulfill all of the reconstructive requisites in one-stage. This new operative technique has never been described before. To deal with a complex head and neck reconstruction, the step-by-step harvesting technique, flap design, and inset of flap are described, giving tips and tricks to avoid jeopardizing its vascularity. A proper match between the bone transplant and native mandible, together with a sufficient amount of tissue for proper oropharyngeal reconstruction was achieved in one stage. Both the functional and aesthetic results were excellent, requiring no further revisions in a second stage. The chimeric fibula free flap with lateral supramalleolar artery perforator flap is a novel, versatile, and useful technique that provides a good opportunity for clinicians and patients to achieve adequate prosthetic rehabilitation and improved aesthetics in reconstruction of postablative extensive oromandibular defects in one stage.
Focus on Dysregulated Adaptive Immunity in Chronic Hepatitis B: A Promising Direction for Immunotherapy
Authors: Zhou Jiaming , Huang Chunhong , Zhu Haihong , Chen Zhi
Published: January 2022

Hepatitis B virus (HBV) infection is a public health problem that endangers global health and is the leading cause for the occurrence and death due to hepatocellular carcinoma. Although nucleotide analogs are excellent in controlling virus replication, they have little effect on the production, stability, and transcription of covalently closed circular DNA (cccDNA) in infected hepatocytes. Moreover, only a small fraction of patients with chronic hepatitis B are cured by interferon therapy. During HBV infection, HBV-specific B cells and T cells are produced. HBV-specific T cells exert antiviral effects through cell lysis and non-cytolytic effector functions, reducing viral intermediates and cccDNA. In addition, HBV-specific B cells produce antibodies that eliminate HBV-infected liver cells through antibody-dependent cell-mediated cytotoxicity of natural killer cells. They can also bind to the hepatitis B surface antigen on the surface of the virus particle, inducing antibody-dependent phagocytosis by Kupffer cells. These responses could be combined with immunotherapy based on antiviral therapy, which may achieve a complete cure for hepatitis B. However, patients with chronic hepatitis B have immune dysfunctions, which challenges immunotherapy implementation. This review focuses on advances in adaptive immunotherapy for chronic viral hepatitis B.
Paracrine Fibroblast Growth Factor-Based Therapy: An Unexpected Panacea for Metabolic-Dysfunction-Associated Fatty Liver Disease (MAFLD)
Authors: Pan Tongtong , Li Ting , Shi Lu , Su Lihuang , Chen Yongping
Published: January 2022

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a group of highly heterogeneous multi-system diseases, which is closely related to metabolic dysfunction and is one of the most important public health problems in the world. Studies have shown that paracrine fibroblast growth factors (FGFs) play an important role in the occurrence and development of MAFLD by regulating glucose and lipid metabolism, inflammation, and fibrosis. This article reviews the latest progress in understanding of the distribution, function, and metabolic regulation of paracrine FGFs, which paves the way for future FGF-based therapies targeting MAFLD.
Curvularia Sinusitis in Leukemic Patients
Authors: Tuktur Wanderimam R. , Katzman Ju Hee , Greene John N.
Published: January 2022

Curvularia species are dematiaceous filamentous fungi that can cause a variety of infections in both immunocompetent and immunocompromised hosts. We present 2 cases of severely immunosuppressed patients with acute invasive fungal sinusitis due to Curvularia species. Both patients had a history of hematologic malignancy with refractory disease and prolonged neutropenia. They presented with facial and sinus pain, which prompted maxillofacial computed tomography that showed acute sinusitis. Subsequently, they underwent nasal endoscopy with a biopsy that revealed a definitive diagnosis of invasive fungal sinusitis. Dematiaceous fungi are responsible for most fungal sinusitis cases, with Curvularia being one of the most common species isolated. Generally, invasive fungal rhinosinusitis may follow a relatively innocuous and nonspecific course. In addition, fungal infections may complicate chronic allergic sinusitis. Computed tomography scan is the first imaging modality of choice, and magnetic resonance imaging has a role in prognostication in acute invasive fungal rhinosinusitis. Endoscopic sinus surgery with biopsy yields a definitive diagnosis and is therapeutic. Management typically includes a combination of surgery and antifungal agents. Severe neutropenia is a significant risk factor for infection and is associated with poor outcomes. Aggressive surgical debridement, combined with antifungal therapy, should be emphasized in leukemic patients despite their prolonged neutropenia and bleeding tendency.