bluuebunny/crossref_metadata_2025_split huggingface dataset:
Japan’s Rise to Naval Prominence
Authors: Kowner Rotem 
Published: June 2022

Abstract
This chapter evaluates the way the battle affected the Japanese actions in the following years and the way it has been commemorated ever since. The battle established Japan’s naval supremacy in East Asian waters and brought it dramatically closer to its desired goal since the outbreak of hostilities: peace negotiations with Russia following their military triumph on sea and land. More importantly, the Battle of Tsushima became a prominent landmark in the rise of the Imperial Japanese Navy. It was celebrated throughout the country and instantly made Admiral Togo a national hero. Thereafter, this doctrine called for the use of a strong battleship force which would destroy an invading fleet in a single stroke as it approached Japan after suffering losses by attrition as it penetrated the nation’s perimeter defences. This chapter shows how the battle remained a reference point for the navy’s Decisive Battle Doctrine in subsequent years and discusses its implications. In addition, the chapter explores the three stages that mark the battle’s memory in Japan during the subsequent century: jubilation, amnesia, and pride.
Conclusion
Authors: Kowner Rotem 
Published: June 2022

Abstract
This chapter offers a comprehensive analysis of the outcomes of the Battle of Tsushima and its significance from historical and naval perspectives. It begins with the question of whether the battle was determined by Russian failure or Japanese success and argues that both sides contributed to the extreme outcomes. The Russians fulfilled all three basic categories of military failure, whereas the Japanese overcame these hurdles by learning, anticipating, and adapting. Despite the Russian inadequacies, the chapter concludes that Tsushima was a ‘great battle’, perhaps even greater than other notable great naval battles. Considering its decisiveness, immediate outcomes, and long-lasting repercussions, the Battle of Tsushima deserves a more central place in historical writing
Light at night in older age is associated with obesity, diabetes, and hypertension
Authors: Kim Minjee , Vu Thanh-Huyen , Maas Matthew B , Braun Rosemary I , Wolf Michael S , Roenneberg Till , Daviglus Martha L , Reid Kathryn J , Zee Phyllis C 
Published: June 2022

AbstractLight at night (LAN) has been associated with negative health consequences and metabolic risk factors. Little is known about the prevalence of LAN in older adults in the United States and its association with CVD risk factors. We tested the hypothesis that LAN in older age is associated with higher prevalence of individual CVD risk factors. Five hundred and fifty-two community-dwelling adults aged 63−84 years underwent an examination of CVD risk factor profiles and 7-day actigraphy recording for activity and light measures. Associations between actigraphy-measured LAN, defined as no light vs. light within the 5-hour nadir (L5), and CVD risk factors, including obesity, diabetes, hypertension, and hypercholesterolemia, were examined, after adjusting for age, sex, race, season of recording, and sleep variables. LAN exposure was associated with a higher prevalence of obesity (multivariable-adjusted odds ratio [OR] 1.82 [95% CI 1.26−2.65]), diabetes (OR 2.00 [1.19−3.43]), and hypertension (OR 1.74 [1.21−2.52]) but not with hypercholesterolemia. LAN was also associated with (1) later timing of lowest light exposure (L5-light) and lowest activity (L5-activity), (2) lower inter-daily stability and amplitude of light exposure and activity, and (3) higher wake after sleep onset. Habitual LAN in older age is associated with concurrent obesity, diabetes, and hypertension. Further research is needed to understand long-term effects of LAN on cardiometabolic risks.
Brain morphometric similarity and flexibility
Authors: Vuksanović Vesna 
Published: June 2022

Abstract

Background
The cerebral cortex is represented through multiple multilayer morphometric similarity networks to study their modular structures. The approach introduces a novel way for studying brain networks' metrics across individuals, and can quantify network properties usually not revealed using conventional network analyses.

Methods
A total of 8 combinations or types of morphometric similarity networks were constructed – 4 combinations of the inter-regional cortical features on 2 brain atlases. The networks' modular structures were investigated by identifying those modular interactions that stay consistent across the combinations of inter-regional morphometric features and individuals.

Results
The results provide evidence of the community structures as the property of (i) cortical lobar divisions, and also as (ii) the product of different combinations of morphometric features used for the construction of the multilayer representations of the cortex. For the first time, this study has mapped out flexible and inflexible morphometric similarity hubs, and evidence has been provided about variations of the modular network topology across the multilayers with age and IQ.

Conclusions
The results contribute to understanding of intra-regional characteristics in cortical interactions, which potentially can be used to map heterogeneous neurodegeneration patterns in diseased brains.
Gene copy number variations at the within-host population level modulate gene expression in a multipartite virus
Authors: Gallet Romain , Di Mattia Jérémy , Ravel Sébastien , Zeddam Jean-Louis , Vitalis Renaud , Michalakis Yannis , Blanc Stéphane 
Published: June 2022

Abstract
Multipartite viruses have a segmented genome, with each segment encapsidated separately. In all multipartite virus species for which the question has been addressed, the distinct segments reproducibly accumulate at a specific and host-dependent relative frequency, defined as the ‘genome formula’. Here, we test the hypothesis that the multipartite genome organization facilitates the regulation of gene expression via changes of the genome formula and thus via gene copy number variations. In a first experiment, the faba bean necrotic stunt virus (FBNSV), whose genome is composed of eight DNA segments each encoding a single gene, was inoculated into faba bean or alfalfa host plants, and the relative concentrations of the DNA segments and their corresponding messenger RNAs (mRNAs) were monitored. In each of the two host species, our analysis consistently showed that the genome formula variations modulate gene expression, the concentration of each genome segment linearly and positively correlating to that of its cognate mRNA but not of the others. In a second experiment, twenty parallel FBNSV lines were transferred from faba bean to alfalfa plants. Upon host switching, the transcription rate of some genome segments changes, but the genome formula is modified in a way that compensates for these changes and maintains a similar ratio between the various viral mRNAs. Interestingly, a deep-sequencing analysis of these twenty FBNSV lineages demonstrated that the host-related genome formula shift operates independently of DNA-segment sequence mutation. Together, our results indicate that nanoviruses are plastic genetic systems, able to transiently adjust gene expression at the population level in changing environments, by modulating the copy number but not the sequence of each of their genes.
Diet and vascular risk
Authors: Gomez-Delgado Francisco , Romero-Cabrera Juan Luis , Perez-Martinez Pablo 
Published: June 2022

Purpose of review
The basis for the prevention and treatment of cardiovascular disease (CVD) inevitably involves lifestyle modification, including dietary pattern (DP). The aim of this review is to address the different models of healthy DP with their peculiarities and nutritional components as well as their importance in the management of CVD.

Recent findings
Classical cardiovascular risk factors such as hypertension, dyslipidaemia and diabetes are strongly influenced by diet and physical activity. However, current evidence supports the role of emerging risk factors such as inflammatory status, oxidative stress and endothelial function in the development of CVD. Likewise, recent evidence explores how healthy DP can modulate CVD risk through these risk factors.

Summary
Although the Mediterranean diet (MedDiet) is the paradigm of the healthy DP in the light of current scientific evidence, there are other DP that we should be aware of due to their results in epidemiological studies, randomized clinical trials (RCTs) and meta-analyses on CVD risk modulation. The best-analysed DP are the MedDiet, Dietary Approaches to Stop Hypertension (DASH), the Nordic DP, the Vegetarian DP, the Portfolio DP, the Low-carbohydrate DP and the Planetary Health diet initiative.
Image-free ultrasound for local and regional vascular stiffness assessment: the ARTSENS Plus
Authors: Nabeel P. M. , Raj Kiran V. , Joseph Jayaraj 
Published: June 2022

Objective:
The combined assessment of vascular health markers is crucial for identifying the cumulative burden of vascular risk factors early on, as well as the extent of vascular aging for effective prediction of future cardiovascular events. This work addresses the need for a currently nonexistent device or system that facilitates such combined assessment in clinical practice and large-scale screening settings. We report an image-free ultrasound device – ARTSENS Plus – developed for the measurement of local and regional arterial stiffness, central and peripheral blood pressure (BP), and vessel dimensions, all in one examination.

Methods:
A preclinical study on 90 asymptomatic individuals verified the device's functionality under ARTERY Society guidelines. The device's accuracy of stiffness measures was validated against the reference measures.

Results:
The interoperator and intraoperator variability was less than 7%. Carotid artery's lumen diameter and local stiffness indices and carotid–femoral regional pulse wave velocity showed excellent agreement with the references (absolute errors were less than 4.1, 9, and 4.1%, respectively). The carotid SBP was 10.02% lower than that of the brachial artery, as expected.

Conclusion:
The study demonstrated the device's ability to perform an effortless and reliable evaluation of the local and regional vascular stiffness and central BP with an accuracy that meets clinical standards.
All-Cause Health Care and Work Loss Burden Associated With Nonsteroidal Anti-Inflammatory Drug and Opioid Treatment in Employed Patients With Osteoarthritis
Authors: Silverman Stuart , Thakkar Sheena , Sell Heather , White Alan G. , Downes Nathaniel , Pajerowski William , Robinson Rebecca L. , Beck Craig G. , Emir Birol , Schepman Patricia 
Published: June 2022

Introduction
This study estimated all-cause health care resource utilization (HRU) and costs and work loss outcomes associated with pain management of employed patients with osteoarthritis of the hip and/or knee.

Methods
Optum Health Care Solutions data were analyzed for employed patients prescribed nonsteroidal anti-inflammatory drugs, tramadol, or nontramadol opioids following diagnoses of osteoarthritis of the hip and/or knee. A pre-post design was used to evaluate changes in all-cause HRU and costs, and work loss days and associated costs.

Results
Costs rose for patients in all three cohorts (up to 198.3% for health care costs [tramadol] and up to 178.7% for work loss costs [tramadol]). Greatest increases in all-cause HRU included inpatient visits (237.9% [nonsteroidal anti-inflammatory drugs]; 600% [tramadol]).

Conclusions
Study results provide evidence of increases in all-cause HRU and costs and work loss days and associated costs.
Integrative deep learning analysis improves colon adenocarcinoma patient stratification at risk for mortality
Authors: Zhou Jie , pour Ali Foroughi , Deirawan Hany , Daaboul Fayez , Aung Thazin , Beydoun Rafic , Ahmed Fahad Shabbir , Chuang Jeffrey H. 
Published: June 2022

AbstractColorectal cancers are the fourth most commonly diagnosed cancer and the second leading cancer in number of deaths. Many clinical variables, pathological features, and genomic signatures are associated with patient risk, but reliable patient stratification in the clinic remains a challenging task. Here we assess how image, clinical, and genomic features can be combined to predict risk. We first observe that deep learning models based only on whole slide images (WSIs) from The Cancer Genome Atlas accurately separate high risk (OS<3years, N=38) from low risk (OS>5years, N=25) patients (AUC=0.81±0.08, 5year survival p-value=2.13e-25, 5year relative risk=5.09±0.05) though such models are less effective at predicting OS for moderate risk (3years<OS<5years, N=45) patients (5year survival p-value=0.5, 5year relative risk=1.32±0.09). However, we find that novel integrative models combining whole slide images, clinical variables, and mutation signatures can improve patient stratification for moderate risk patients (5year survival p-value=6.69e-30, 5year relative risk=5.32±0.07). Our integrative model combining image and clinical variables is also effective on an independent pathology dataset generated by our team (3year survival p-value=1.14e-09, 5year survival p-value=2.15e-05, 3year relative risk=3.25±0.06, 5year relative-risk=3.07±0.08). The integrative model substantially outperforms models using only images or only clinical variables, indicating beneficial cross-talk between the data types. Pathologist review of image-based heatmaps suggests that nuclear shape, nuclear size pleomorphism, intense cellularity, and abnormal structures are associated with high risk, while low risk regions tend to have more regular and small cells. The improved stratification of colorectal cancer patients from our computational methods can be beneficial for preemptive development of management and treatment plans for individual patients, as well as for informed enrollment of patients in clinical trials.
Ebonyunderpins Batesian mimicry in an insect melanic polymorphism
Authors: Foster Brodie J. , McCulloch Graham A. , Foster Yasmin , Kroos Gracie C. , Waters Jonathan M. 
Published: June 2022

AbstractThe evolution of Batesian mimicry – whereby harmless species avoid predation through their resemblance to harmful species – has long intrigued biologists. In rare cases, such mimicry systems can be highly dynamic, being maintained via frequency-dependent selection on intraspecific polymorphisms, in which only some individuals within a population resemble a noxious ‘model’. Here, we use genomic approaches to identify the genetic basis of a striking mimicry polymorphism within a widespread New Zealand stonefly complex. Specifically, highly melanised specimens ofZelandoperlaclosely resemble an aposematic stonefly (Austroperla cyrene) well-known for its production of hydrogen cyanide. We assess convergence in the colour pattern of these two species, compare their relative palatability to predators, and use genome-wide association mapping to elucidate the genetic basis of this mimicry polymorphism. Our analysis reveals that melanisedZelandoperlaoverlap significantly withAustroperlain colour space, but are significantly more palatable to predators, indicating that they are indeed Batesian mimics. Analysis of 194,773 genome-wide SNPs reveals a strong outlier locus (ebony) differentiating melanic (mimic) versus non-melanic phenotypes. Asebonyhas a well-documented role in insect melanin biosynthesis, our findings highlight its conserved function across deeply divergent hexapod lineages. Distributional records suggest a link between the occurrence ofZelandoperlamimics and forested ecosystems where the modelAustroperlais abundant, suggesting the potential for adaptive shifts in this system underpinned by environmental change.
GM-CSF drives immune-mediated glomerular disease by licensing monocyte-derived cells to produce MMP12
Authors: Paust Hans-Joachim , Song Ning , De Feo Donatella , Asada Nariaki , Tuzlak Selma , Zhao Yu , Riedel Jan-Hendrik , Hellmig Malte , Sivayoganathan Amirrtavarshni , Peters Anett , Kaffke Anna , Borchers Alina , Wenzel Ulrich O. , Steinmetz Oliver M. , Tiegs Gisa , Meister Elisabeth , Lindenmeyer Maja T. , Hoxha Elion , Stahl Rolf A.K. , Huber Tobias B. , Bonn Stefan , Meyer-Schwesinger Catherine , Wiech Thorsten , Turner Jan-Eric , Becher Burkhard , Krebs Christian F. , Panzer Ulf 
Published: June 2022

ABSTRACTGlomerulonephritis is a group of immune-mediated diseases that cause inflammation within the glomerulus and adjacent compartments of the kidney and is a major cause of end-stage renal disease. T cells are among the main drivers of glomerulonephritis. However, the T cell subsets, cytokine networks, and downstream effector mechanisms that lead to renal tissue injury are largely unknown, which has hindered the development of targeted therapies.Here we identify a population of GM-CSF-producing T cells that accumulates in the kidneys of patients with ANCA-associated glomerulonephritis, infiltrates the renal tissue in a mouse model of glomerulonephritis, and promotes tissue destruction and loss of renal function. Mechanistically, we show that GM-CSF producing T cells licence monocyte-derived cells to produce matrix metalloproteinase 12 (MMP12), which cleaves components of the glomerular basement membrane and exacerbates renal pathology. These findings provide a mechanistic rationale for the immunopathology of T cell-mediated diseases and identify the “GM-CSF – monocyte-derived cells – MMP12” pathway as a promising therapeutic target in treatment of glomerulonephritis.
Suppression of YAP Safeguards Human Naïve Pluripotency
Authors: Dattani Anish , Huang Tao , Smith Austin , Guo Ge 
Published: June 2022

ABSTRACTPropagation of human naïve pluripotent stem cells (nPSCs) requires inhibition of MEK/ERK signalling. However, MEK/ERK inhibition also induces differentiation into trophectoderm (TE). Therefore, robust self-renewal requires active suppression of TE fate. Tankyrase inhibition using XAV939 has been shown to stabilise human nPSCs. Here we dissect the mechanism of this effect. Tankyrase inhibition blocks canonical Wnt/β-catenin signalling. However, nPSCs depleted of β-catenin remain dependent on XAV939. We show that XAV939 prevents TE induction by suppressing YAP activity independent of β-catenin. Tankyrase inhibition stabilises angiomotin, which reduces nuclear translocation of YAP1/TAZ. Upon deletion of Angiomotin-family members AMOT and AMOTL2, nuclear YAP increases and XAV939 fails to prevent TE induction. Conversely, nPSCs lacking YAP1 fail to undergo TE differentiation and sustain efficient self-renewal without XAV939. These findings explain the distinct requirement for tankyrase inhibition in human but not mouse naïve PSCs and highlight the pivotal role of YAP in human naïve pluripotency.
Autoantigenic properties of the aminoacyl tRNA synthetase family in idiopathic inflammatory myopathies
Authors: Preger Charlotta , Notarnicola Antonella , Hellström Cecilia , Wigren Edvard , Fernandes-Cerqueira Cátia , Idborg Helena , Lundberg Ingrid E. , Persson Helena , Gräslund Susanne , Jakobsson Per-Johan 
Published: June 2022

ABSTRACTObjectivesAutoantibodies are thought to play a key role in the pathogenesis of idiopathic inflammatory myopathies (IIM). However, up to 40% of IIM patients, even those with clinical manifestations of anti-synthetase syndrome (ASSD), test seronegative to all known myositis-specific autoantibodies (MSAs). We hypothesized the existence of new potential autoantigens among human cytoplasmic aminoacyl tRNA synthetases (aaRS) in patients with IIM.MethodsPlasma samples and clinical data from 217 patients with, 50 patients with ASSD, 165 without, and two with unknown ASSD status were included retrospectively, as well as serum from 156 age/sex-matched population controls. Samples were screened using a multiplex bead array assay for presence of autoantibodies against a panel of 118 recombinant protein variants, representing 33 myositis-related proteins, including all 19 cytoplasmic aaRS.ResultsWe identified reactivity towards 16 aaRS in 72 of the 217 patients. Twelve patients displayed reactivity against nine novel aaRS. The novel autoantibody specificities were detected in four patients previously seronegative for MSAs and in eight with previously detected MSAs. We also confirmed reactivity to four of the most common aaRS (Jo1, PL12, PL7, and EJ (n=45)) and identified patients positive for anti-Zo, -KS, and -HA (n=10) that were not previously tested. A low frequency of anti-aaRS autoantibodies was detected in controls.ConclusionOur results suggest that most, if not all, cytoplasmic aaRS may become autoantigenic. Autoantibodies against new aaRS may be found in plasma of patients previously classified as seronegative with potential high clinical relevance.
Hepatic pyruvate and alanine metabolism are critical and complementary for maintenance of antioxidant capacity and resistance to oxidative insult in mice
Authors: Yiew Nicole K.H. , Vazquez Joel H. , Martino Michael R. , Kennon-McGill Stefanie , Price Jake R. , Allard Felicia D. , Yee Eric U. , James Laura P. , McCommis Kyle S. , Finck Brian N. , McGill Mitchell R. 
Published: June 2022

ABSTRACTPyruvate is a critical intermediary metabolite in gluconeogenesis, lipogenesis, as well as NADH production. As a result, there is growing interest in targeting the mitochondrial pyruvate carrier (MPC) complex in liver and metabolic diseases. However, recent in vitro data indicate that MPC inhibition diverts glutamine/glutamate away from glutathione synthesis and toward glutaminolysis to compensate for loss of pyruvate oxidation, possibly sensitizing cells to oxidative insult. Here, we explored this using the clinically relevant acetaminophen (APAP) overdose model of acute liver injury, which is driven by oxidative stress. We report that MPC inhibition does indeed sensitize the liver to APAP-induced injury in vivo, but only with concomitant loss of alanine aminotransferase 2 (ALT2). Pharmacologic and genetic manipulation of neither MPC2 nor ALT2 alone affected APAP toxicity, but liver-specific double knockout (DKO) of these proteins significantly worsened the liver damage. Further investigation confirmed that DKO impaired glutathione synthesis and increased urea cycle flux, consistent with increased glutaminolysis. Furthermore, APAP toxicity was exacerbated by inhibition of both the MPC and ALT in vitro. Thus, increased glutaminolysis and susceptibility to oxidative stress requires loss of both the MPC and ALT2 in vivo and exacerbates them in vitro. Finally, induction of ALT2 reduced APAP-induced injury.
Measuring Neuronal Avalanches to inform Brain-Computer Interfaces
Authors: Corsi Marie-Constance , Sorrentino Pierpaolo , Schwartz Denis , George Nathalie , Gollo Leonardo L. , Chevallier Sylvain , Hugueville Laurent , Kahn Ari E. , Dupont Sophie , Bassett Danielle S. , Jirsa Viktor , De Vico Fallani Fabrizio 
Published: June 2022

AbstractLarge-scale interactions among multiple brain regions manifest as bursts of activations called neuronal avalanches, which reconfigure according to the task at hand and, hence, might constitute natural candidates to design brain-computer interfaces (BCI). To test this hypothesis, we used source-reconstructed magneto/electroencephalography, during resting state and a motor imagery task performed within a BCI protocol. To track the probability that an avalanche would spread across any two regions we built an avalanche transition matrix (ATM) and demonstrated that the edges whose transition probabilities significantly differed between conditions hinged selectively on premotor regions in all subjects. Furthermore, we showed that the topology of the ATMs allows task-decoding above the current gold standard. Hence, our results suggest that Neuronal Avalanches might capture interpretable differences between tasks that can be used to inform brain-computer interfaces.