bluuebunny/crossref_metadata_2025 huggingface dataset:
Haemorrhage of human foetal cortex associated with SARS-CoV-2 infection
Authors: Massimo Marco , Barelli Carlotta , Moreno Catalina , Collesi Chiara , Holloway Rebecca K , Crespo Berta , Zentilin Lorena , Williams Anna , Miron Veronique E , Giacca Mauro , Long Katherine R
Published: January 2023

Maternal viral infection and immune response are known to increase the risk of altered development of the foetal brain. Given the ongoing global pandemic of coronavirus disease 2019 (COVID-19), investigating the impact of SARS-CoV-2 on foetal brain health is of critical importance. Here, we report the presence of SARS-CoV-2 in first and second trimester foetal brain tissue in association with cortical haemorrhages. SARS-CoV-2 spike protein was sparsely detected within progenitors and neurons of the cortex itself, but was abundant in the choroid plexus of haemorrhagic samples. SARS-CoV-2 was also sparsely detected in placenta, amnion and umbilical cord tissues. Cortical haemorrhages were linked to a reduction in blood vessel integrity and an increase in immune cell infiltration into the foetal brain. Our findings indicate that SARS-CoV-2 infection may affect the foetal brain during early gestation and highlight the need for further study of its impact on subsequent neurological development.
Prospective study and validation of early warning marker discovery based on integrating multi-omics analysis in severe burn patients with sepsis
Authors: Huang Jiamin , Chen Yi , Guo Zaiwen , Yu Yanzhen , Zhang Yi , Li Pingsong , Shi Lei , Lv Guozhong , Sun Bingwei
Published: January 2023

Background

Early detection, timely diagnosis and rapid response are essential for case management and precautions of burn-associated sepsis. However, studies on indicators for early warning and intervention have rarely been conducted. This study was performed to better understand the pathophysiological changes and targets for prevention of severe burn injuries.

Methods

We conducted a multi-center, prospective multi-omics study, including genomics, microRNAomics, proteomics and single-cell transcriptomics, in 60 patients with severe burn injuries. A mouse model of severe burn injuries was also constructed to verify the early warning ability and therapeutic effects of potential markers.

Results

Through genomic analysis, we identified seven important susceptibility genes (DNAH11, LAMA2, ABCA2, ZFAND4, CEP290, MUC20 and ENTPD1) in patients with severe burn injuries complicated with sepsis. Through plasma miRNAomics studies, we identified four miRNAs (hsa-miR-16-5p, hsa-miR-185-5p, hsa-miR-451a and hsa-miR-423-5p) that may serve as early warning markers of burn-associated sepsis. A proteomic study indicated the changes in abundance of major proteins at different time points after severe burn injury and revealed the candidate early warning markers S100A8 and SERPINA10. In addition, the proteomic analysis indicated that neutrophils play an important role in the pathogenesis of severe burn injuries, as also supported by findings from single-cell transcriptome sequencing of neutrophils. Through further studies on severely burned mice, we determined that S100A8 is also a potential early therapeutic target for severe burn injuries, beyond being an early warning indicator.

Conclusions

Our multi-omics study identified seven susceptibility genes, four miRNAs and two proteins as early warning markers for severe burn-associated sepsis. In severe burn-associated sepsis, the protein S100A8 has both warning and therapeutic effects.
Updating the Adherence–Response for Oral Emtricitabine/Tenofovir Disoproxil Fumarate for Human Immunodeficiency Virus Pre-Exposure Prophylaxis Among Cisgender Women
Authors: Anderson Peter L , Marzinke Mark A , Glidden David V
Published: January 2023

Using intraerythrocytic tenofovir-diphosphate data from the emtricitabine/tenofovir disoproxil fumarate arms of HIV Prevention Trials Network (HPTN) 083 (men) and HPTN 084 (women), approximately 99% efficacy was achieved at a lower adherence threshold in HPTN 083 (≥2 doses/week) compared with HPTN 084 (daily), suggesting higher adherence is necessary for women vs men.
Accelerating Human Immunodeficiency Virus Self-Testing in the United States: A Call to Action
Authors: Ma Stephany , MacGowan Robin J , Mermin Jonathan H , Owen S Michele , Manabe Yukari C
Published: January 2023

Human immunodeficiency virus (HIV) self-testing has emerged as a tool to increase the proportion of people to know their status. Since the first HIV self-test was approved in 2012 by the US Food and Drug Administration (FDA), global access to HIV self-tests has been bolstered by public-private partnerships to ensure equitable access in low- and middle-income countries. However, no company has applied for FDA clearance in a decade. We highlight the potential benefits to reclassifying HIV self-tests from class III to class II.
Development of an LC-MRM-MS-Based Candidate Reference Measurement Procedure for Standardization of Serum Apolipoprotein (a) Tests
Authors: Ruhaak L Renee , Romijn Fred P H T M , Begcevic Brkovic Ilijana , Kuklenyik Zsusanna , Dittrich Julia , Ceglarek Uta , Hoofnagle Andrew N , Althaus Harald , Angles-Cano Eduardo , Coassin Stefan , Delatour Vincent , Deprez Liesbet , Dikaios Ioannis , Kostner Gerhard M , Kronenberg Florian , Lyle Alicia , Prinzing Urban , Vesper Hubert W , Cobbaert Christa M
Published: January 2023

Background

Medical results generated by European CE Marking for In Vitro Diagnostic or in-house tests should be traceable to higher order reference measurement systems (RMS), such as International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)-endorsed reference measurement procedures (RMPs) and reference materials. Currently, serum apolipoprotein (a) [apo(a)] is recognized as a novel risk factor for cardiovascular risk assessment and patient management. The former RMS for serum apo(a) is no longer available; consequently, an International System of Units (SI)-traceable, ideally multiplexed, and sustainable RMS for apo(a) is needed.

Methods

A mass spectrometry (MS)-based candidate RMP (cRMP) for apo(a) was developed using quantitative bottom-up proteomics targeting 3 proteotypic peptides. The method was provisionally validated according to ISO 15193 using a single human serum based calibrator traceable to the former WHO-IFCC RMS.

Results

The quantitation of serum apo(a) was by design independent of its size polymorphism, was linear from 3.8 to 456 nmol/L, and had a lower limit of quantitation for apo(a) of 3.8 nmol/L using peptide LFLEPTQADIALLK. Interpeptide agreement showed Pearson Rs of 0.987 and 0.984 for peptides GISSTVTGR and TPENYPNAGLTR, and method comparison indicated good correspondence (slopes 0.977, 1.033, and 1.085 for LFLEPTQADIALLK, GISSTVTGR, and TPENYPNAGLTR). Average within-laboratory imprecision of the cRMP was 8.9%, 11.9%, and 12.8% for the 3 peptides.

Conclusions

A robust, antibody-independent, MS-based cRMP was developed as higher order RMP and an essential part of the apo(a) traceability chain and future RMS. The cRMP fulfils predefined analytical performance specifications, making it a promising RMP candidate in an SI-traceable MS-based RMS for apo(a).
High-Density Lipoprotein Lipidomics in Chronic Kidney Disease
Authors: Lidgard Benjamin , Hoofnagle Andrew N , Zelnick Leila R , de Boer Ian H , Fretts Amanda M , Kestenbaum Bryan R , Lemaitre Rozenn N , Robinson-Cohen Cassianne , Bansal Nisha
Published: January 2023

Background

Patients with chronic kidney disease (CKD) have dysfunctional high-density lipoprotein (HDL) particles as compared with the general population. Understanding the lipid composition of HDL may provide mechanistic insight. We tested associations of estimated glomerular filtration rate (eGFR) and albuminuria with relative HDL abundance of ceramides, sphingomyelins, and phosphatidylcholines in participants with CKD.

Methods

We studied 490 participants with CKD from the Seattle Kidney Study. HDL was isolated from plasma; targeted lipidomics was used to quantify the relative abundance of ceramides, sphingomyelins, and phosphatidylcholines per 10 µg of total HDL protein. We evaluated the associations of eGFR and albuminuria with levels of individual lipids and lipid classes (including 7 ceramides, 6 sphingomyelins, and 24 phosphatidylcholines) using multivariable linear regression, controlling for multiple comparisons via the false discovery rate.

Results

The mean (SD) eGFR was 45 (24) mL/min/1.73 m2; the median (IQR[interquartile range]) albuminuria was 108 (16, 686) mg/g (12.2 [1.8, 77.6] mg/mmol) urine creatinine. After adjusting for demographics, past medical history, laboratory values, and medication use, eGFR was not associated with higher relative abundance of any class of lipids or individual lipids. Greater albuminuria was significantly associated with a higher relative abundance of total ceramides and moderate–long R-chain sphingomyelins, ceramides 22:0 and 24:1, hexosylceramide 16:0, sphingomyelin 16:0, and phosphatidylcholines 29:0, 30:1, and 38:2; the strongest association was for hexosylceramide 16:0 (increase per doubling of urine albumin to creatinine ratio 0.022 (95% CI, 0.012–0.032).

Conclusions

Greater albuminuria was significantly associated with specific alterations in the lipid composition of HDL in participants with CKD.
Association of central obesity with unique cardiac remodelling in young adults born small for gestational age
Authors: Bernardino Gabriel , Sepúlveda-Martínez Álvaro , Rodríguez-López Mérida , Prat-González Susanna , Pajuelo Carolina , Perea Rosario J , Caralt Maria T , Crovetto Francesca , González Ballester Miguel A , Sitges Marta , Bijnens Bart , Crispi Fàtima
Published: January 2023

Aims

Being born small for gestational age (SGA, 10% of all births) is associated with increased risk of cardiovascular mortality in adulthood together with lower exercise tolerance, but mechanistic pathways are unclear. Central obesity is known to worsen cardiovascular outcomes, but it is uncertain how it affects the heart in adults born SGA. We aimed to assess whether central obesity makes young adults born SGA more susceptible to cardiac remodelling and dysfunction.

Methods and results

A perinatal cohort from a tertiary university hospital in Spain of young adults (30–40 years) randomly selected, 80 born SGA (birth weight below 10th centile) and 75 with normal birth weight (controls) was recruited. We studied the associations between SGA and central obesity (measured via the hip-to-waist ratio and used as a continuous variable) and cardiac regional structure and function, assessed by cardiac magnetic resonance using statistical shape analysis. Both SGA and waist-to-hip were highly associated to cardiac shape (F = 3.94, P < 0.001; F = 5.18, P < 0.001 respectively) with a statistically significant interaction (F = 2.29, P = 0.02). While controls tend to increase left ventricular end-diastolic volumes, mass and stroke volume with increasing waist-to-hip ratio, young adults born SGA showed a unique response with inability to increase cardiac dimensions or mass resulting in reduced stroke volume and exercise capacity.

Conclusion

SGA young adults show a unique cardiac adaptation to central obesity. These results support considering SGA as a risk factor that may benefit from preventive strategies to reduce cardiometabolic risk.
The interaction of forced expiratory volume in 1 s and N-terminal pro-B-type natriuretic peptide with outcomes after transcatheter aortic valve replacement
Authors: Crestanello Juan A , Greason Kevin L , Mathew Jessey , Eleid Mackram F , Nkomo Vuyisile T , Rihal Charanjit S , Bagameri Gabor , Holmes David R , Pislaru Sorin V , Sandhu Gurpreet S , Lee Alexander T , King Katherine S , Alkhouli Mohamad
Published: January 2023

OBJECTIVES

Low forced expiratory volume in 1 s (FEV1) and elevated N-terminal pro-B-type natriuretic peptide (NT-Pro-BNP) have been individually associated with poor outcomes after transcatheter aortic valve replacement (TAVR). We hypothesized a combination of the 2 would provide prognostic indication after TAVR.

METHODS

We categorized 871 patients who received TAVR from 2008 to 2018 into 4 groups according to baseline FEV1 (<60% or ≥60% predicted) and NT-Pro-BNP (<1601 or ≥1601 pg/ml): group A (n = 312, high FEV1, low NT-Pro-BNP), group B (n = 275, high FEV1, high NT-Pro-BNP), group C (n = 123 low FEV1, low NT-Pro-BNP) and group D (n = 161, low FEV1, high NT-Pro-BNP). The primary end point was survival at 1 and 5 years.

RESULTS

Patients in group A had more severe aortic stenosis and achieved the best long-term survival at 1 [93% (95% CI: 90–96)] and 5 [45.3% (95% CI: 35.4–58)] years. Low FEV1 and high NT-Pro-BNP (group D) patients had more severe symptoms, higher Society of Thoracic Surgeons predicted risk of operative mortality, lower ejection fraction and aortic valve gradient at baseline. Patients in group D had the worst survival at 1 [76% (95% CI: 69–83)] and 5 years [13.1% (95% CI: 7–25)], hazard ratio compared to group A: 2.29 (95% CI: 1.6–3.2, P < 0.001) with 25.7% of patients in New York Heart Association class III–IV. Patients in groups B and C had intermediate outcomes.

CONCLUSIONS

The combination of FEV1 and NT-Pro-BNP stratifies patients into 4 groups with distinct risk profiles and clinical outcomes. Patients with low FEV1 and high NT-Pro-BNP have increased comorbidities, poor functional outcomes and decreased long-term survival after TAVR.
Dyskeratosis Congenita Links Telomere Attrition to  Age-Related Systemic Energetics
Authors: James Emma Naomi , Sagi-Kiss Virag , Bennett Mark , Mycielska Maria Elzbieta , Karen-Ng Lee Peng , Roberts Terry , Matta Sheila , Dokal Inderjeet , Bundy Jacob Guy , Parkinson Eric Kenneth
Published: January 2023

The underlying mechanisms of plasma metabolite signatures of human aging and age-related diseases are not clear but telomere attrition and dysfunction are central to both. Dyskeratosis congenita (DC) is associated with mutations in the telomerase enzyme complex (TERT, TERC, and DKC1) and progressive telomere attrition. We analyzed the effect of telomere attrition on senescence-associated metabolites in fibroblast-conditioned media and DC patient plasma. Samples were analyzed by gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. We showed extracellular citrate was repressed by canonical telomerase function in vitro and associated with DC leukocyte telomere attrition in vivo, leading to the hypothesis that altered citrate metabolism detects telomere dysfunction. However, elevated citrate and senescence factors only weakly distinguished DC patients from controls, whereas elevated levels of other tricarboxylic acid cycle (TCA) metabolites, lactate, and especially pyruvate distinguished them with high significance. The DC plasma signature most resembled that of patients with loss of function pyruvate dehydrogenase complex mutations and that of older subjects but significantly not those of type 2 diabetes, lactic acidosis, or elevated mitochondrial reactive oxygen species. Additionally, our data are consistent with further metabolism of citrate and lactate in the liver and kidneys. Citrate uptake in certain organs modulates age-related disease in mice and our data have similarities with age-related disease signatures in humans. Our results have implications for the role of telomere dysfunction in human aging in addition to its early diagnosis and the monitoring of anti-senescence therapeutics, especially those designed to improve telomere function.
Galyean appreciation club review: a holistic perspective of the societal relevance of beef production and its impacts on climate change
Authors: Tedeschi Luis O , Beauchemin Karen A
Published: January 2023

This article provides a science-based, data-driven perspective on the relevance of the beef herd in the U.S. to our society and greenhouse gas (GHG) contribution to climate change. Cattle operations are subject to criticism for their environmental burden, often based on incomplete information disseminated about their social, economic, nutritional, and ecological benefits and detriments. The 2019 data published by the U.S. Environmental Protection Agency reported that U.S. beef cattle emitted 22.6% of the total agricultural emissions, representing about 2.2% of the total anthropogenic emissions of CO2 equivalent (CO2e). Simulations from a computer model developed to address global energy and climate challenges, set to use extreme improvements in livestock and crop production systems, indicated a potential reduction in global CO2e emissions of 4.6% but without significant enhancement in the temperature change by 2030. There are many natural and anthropogenic sources of CH4 emissions. Contrary to the increased contribution of peatlands and water reservoirs to atmospheric CO2e, the steady decrease in the U.S. cattle population is estimated to have reduced its methane (CH4) emissions by about 30% from 1975 to 2021. This CH4 emission deacceleration of 2.46 Mt CO2e/yr2 might be even more significant than reported. Many opportunities exist to mitigate CH4 emissions of beef production, leading to a realistic prospect of a 5% to 15% reduction in the short term after considering the overlapping impacts of combined strategies. Reduction strategies include feeding synthetic chemicals that inactivate the methyl-coenzyme M reductase (the enzyme that catalyzes the last step of methanogenesis in the rumen), red seaweed or algae extracts, ionophore antibiotics, phytochemicals (e.g., condensed tannins and essential oils), and other nutritional manipulations. The proposed net-zero concept might not solve the global warming problem because it will only balance future anthropogenic GHG emissions with anthropogenic removals, leaving global warming on a standby state. Recommendations for consuming red meat products should consider human nutrition, health, and disease and remain independent of controversial evidence of causational relationships with perceived negative environmental impacts of beef production that are not based on scientific data.
To Like or Not to Like? An Experimental Study on Relational Closeness, Social Grooming, Reciprocity, and Emotions in Social Media Liking
Authors: Stsiampkouskaya Kseniya , Joinson Adam , Piwek Lukasz
Published: January 2023

We conducted a randomized-controlled experiment with 201 participants to investigate the effects of relationship closeness, emotions, and the receipt of Likes on reciprocal Liking behaviors. We found that individuals engaged in interchange-oriented social grooming by giving Likes to close friends regardless of whether they had received Likes from them before. However, when relationship closeness was low, participants mirrored their acquaintances’ behavior by reciprocating Likes for Likes. Additionally, high-arousal positive emotions mediated the effects of receiving Likes on the intention to Like other users’ content, but this result only held true when relational closeness was not accounted for in the model. Our study explains why people give Likes on social media and what factors shape their Liking intentions. The results of our study contribute to the existing knowledge of the social norm of reciprocity, social grooming, emotion regulation, relational closeness, and social media Liking.
Sunitinib therapy for imatinib-resistant and/or intolerant gastrointestinal stromal tumors: comparison of safety and efficacy between standard and reduced dosage regimens
Authors: Sasaki Kenta , Kanda Tatsuo , Matsumoto Yoshifumi , Ishikawa Takashi , Hirota Seiichi , Saijo Yasuo
Published: January 2023

Background

Sunitinib therapy for patients with imatinib-resistant and/or intolerant gastrointestinal stromal tumors (GISTs) often causes severe adverse events (AEs) that lead to treatment discontinuation.

Methods

We retrospectively reviewed the clinical records of imatinib-resistant and/or intolerant GIST patients who underwent sunitinib therapy in our institutions between 2007 and 2020. Forty-one patients were enrolled and divided into two groups on the basis of the starting dosage: the standard dosage group (50 mg/day, 21 patients) and the reduced dosage group (37.5 mg/day, 20 patients). Tolerability, safety and clinical efficacy of the two groups were compared.

Results

Three patients (14%) in the standard dosage group and another three (15%) in the reduced dosage group (P = 1.000) discontinued sunitinib therapy because of AEs. The incidences of grade 3 or more severe treatment-related AEs were 90 and 75%, respectively (P = 0.238). Two possible treatment-related deaths were noted in the standard dosage group. Clinical efficacy was comparable between the two groups: median time to treatment failure and overall survival were 4.5 months [interquartile range (IQR), 3.6–9.0] and 13.7 months (IQR, 7.5–22.9) in the standard dosage group and 4.6 months (IQR, 2.7–17.0) and 13.4 months (IQR, 9.3–36.8) in the reduced dosage group, respectively.

Conclusions

The reduced dosage of 37.5 mg sunitinib tended to decrease toxicity and the incidences of severe AEs and treatment-related deaths. This reduced dosage regimen showed equivalent clinical efficacy including patient survival. The reduced dosage of 37.5 mg sunitinib can be adopted as an alternative therapy for patients with imatinib-resistant and/or intolerant GISTs.
LncRNA15691 promotes T-ALL infiltration by upregulating CCR9 via increased MATR3 stability
Authors: Zeng Xingruo , Lei Yufei , Pan Shan , Sun Jiaxing , He Hengjing , Xiao Di , Jamal Muhammad , Shen Hui , Zhou Fuling , Shao Liang , Zhang Quiping
Published: January 2023

Our previous studies demonstrated that CCR9 plays an important role in several aspects of T-cell acute lymphoblastic leukemia progression and that CCR9 is a potential therapeutic target. However, the underlying mechanism that regulates CCR9 expression remains incompletely understood. In this study, bioinformatics analysis and validation in clinical samples revealed the lncRNA15691 to be positively correlated with CCR9 mRNA expression and significantly upregulated in T-cell acute lymphoblastic leukemia samples and CCR9high T-cell acute lymphoblastic leukemia cell lines. LncRNA15691, a previously uncharacterized lncRNA, was found to be located in both the cytoplasm and the nucleus via fluorescence in situ hybridization assay. In addition, lncRNA15691 upregulated the expression of CCR9 and was involved in T-cell acute lymphoblastic leukemia cell invasion. In vivo experiments showed that lncRNA15691 promoted leukemia cell homing/infiltration into the bone marrow, blood, and spleen, whereas the CCR9 ligand, CCL25, augmented the extramedullary infiltration of CCR9low leukemia cells overexpressing lncRNA15691 into blood, spleen, and liver. Subsequently, RNA protein pull-down assays, coupled with liquid chromatography–tandem mass spectrometry, were used to uncover potential lncRNA15691-interacting proteins, which were then validated by RNA immunoprecipitation. These mechanistic studies revealed that lncRNA15691 upregulated CCR9 expression via directly binding to and stabilizing MATR3 by inhibiting its nuclear degradation mediated by PKA. Collectively, our study revealed a novel mechanism of regulating CCR9 expression and implicated lncRNA15691 as a potential novel biomarker for T-cell acute lymphoblastic leukemia infiltration.
Single-cell transcriptome sequencing of macrophages in common cardiovascular diseases
Authors: Li Lanfang , Ma Qiuxiao , Wang Min , Mou Junyu , Han Yanwei , Wang Jialu , Ye Jingxue , Sun Guibo
Published: January 2023

Macrophages are strategically located throughout the body at key sites in the immune system. A key feature in atherosclerosis is the uptake and accumulation of lipoproteins by arterial macrophages, leading to the formation of foam cells. After myocardial infarction, macrophages derived from monocytes infiltrate the infarcted heart. Macrophages are also closely related to adverse remodeling after heart failure. An in-depth understanding of the functions and characteristics of macrophages is required to study heart health and pathophysiological processes; however, the heterogeneity and plasticity explained by the classic M1/M2 macrophage paradigm are too limited. Single-cell sequencing is a high-throughput sequencing technique that enables the sequencing of the genome or transcriptome of a single cell. It effectively complements the heterogeneity of gene expression in a single cell that is ignored by conventional sequencing and can give valuable insights into the development of complex diseases. In the present review, we summarize the available research on the application of single-cell transcriptome sequencing to study the changes in macrophages during common cardiovascular diseases, such as atherosclerosis, myocardial infarction, and heart failure. This article also discusses the contribution of this knowledge to understanding the pathogenesis, development, diagnosis, and treatment of heart diseases.
A novel Lagrangian formulation to construct relativistic rotating stars: towards its application to their evolution calculations
Authors: Okawa Hirotada , Fujisawa Kotaro , Yasutake Nobutoshi , Ogata Misa , Yamamoto Yu , Yamada Shoichi
Published: January 2023

We present a new formulation to construct numerically equilibrium configurations of rotating stars in general relativity. Having in mind the application to their quasi-static evolutions on a secular time-scale, we adopt a Lagrangian formulation of our own devising, in which we solve force-balance equations to seek for the positions of fluid elements corresponding to the grid points, instead of the ordinary Eulerian formulation. Unlike previous works in the literature, we do not employ the first integral of the Euler equation, which is not obtained analytically in general. We assign a mass, specific angular momentum and entropy to each fluid element in contrast to the previous Eulerian methods, in which the spatial distribution of the angular velocity or angular momentum is specified. These distributions are determined after the positions of all fluid elements (or grid points) are derived in our formulation. We solve the large system of algebraic non-linear equations that are obtained by discretizing the time-independent Euler and Einstein equations in the finite-element method by using our new multidimensional root-finding scheme, named the W4 method. To demonstrate the capability of our new formulation, we construct some rotational configurations, both barotropic and baroclinic. As toy models, we also solve three evolutionary sequences that mimic the cooling, mass-loss, and mass-accretion.
Mantle mineralogy limits to rocky planet water inventories
Authors: Guimond Claire Marie , Shorttle Oliver , Rudge John F
Published: January 2023

Nominally anhydrous minerals in rocky planet mantles can sequester multiple Earth-oceans’ worth of water. Mantle water storage capacities therefore provide an important constraint on planet water inventories. Here we predict silicate mantle water capacities from the thermodynamically-limited solubility of water in their constituent minerals. We report the variability of upper mantle and bulk mantle water capacities due to (i) host star refractory element abundances that set mantle mineralogy, (ii) realistic mantle temperature scenarios, and (iii) planet mass. We find that transition zone minerals almost unfailingly dominate the water capacity of the mantle for planets of up to ∼1.5 Earth masses, possibly creating a bottleneck to deep water transport, although the transition zone water capacity discontinuity is less pronounced at lower Mg/Si. The pressure of the ringwoodite-perovskite phase boundary defining the lower mantle is roughly constant, so the contribution of the upper mantle reservoir becomes less important for larger planets. If perovskite and postperovskite are relatively dry, then increasingly massive rocky planets would have increasingly smaller fractional interior water capacities. In practice, our results represent initial water concentration profiles in planetary mantles where their primordial magma oceans are water-saturated. This work is a step towards understanding planetary deep water cycling, thermal evolution as mediated by rheology and melting, and the frequency of ocean planets.
Investigating the high time-resolution statistics of pulsar radio signals using spectral self-noise
Authors: Faustmann A , Schwardt L , van Tonder V , Gilmore J , Buchner S
Published: January 2023

While observations of the stationary component of pulsar radio signals have in many ways formed the basis of our understanding of radio pulsars, the statistical deviations of these signals contain information that has become increasingly relevant. Using high time–frequency resolution data from the MeerKAT telescope, we study the self-noise of the autocorrelation function of six radio pulsars. The self-noise of the autocorrelation function is used to investigate the statistics of the observed radio signals on nanosecond time-scales and for five pulsars it is found to deviate from the expected form for a Gaussian process. Comparing the measured distribution of the intensity fluctuations of the on-pulse window to simulated models, we find that a mixture model comprising a Gaussian process and a Bernoulli-sampled Gaussian process is able to produce the excess self-noise while also producing the observed distribution of intensities. The parameters of the mixture model describing the signals are estimated for three of the pulsars in our sample group. Studies of the statistics presented in this work provide observational information for constraining the numerous theories of pulsar radio emission mechanisms. The mixture model suggested in this work would produce excess timing residuals for high signal-to-noise ratio observations when compared to that expected for a Gaussian process. Additionally, the measure of spectral self-noise provides a means of separating Gaussian and non-Gaussian processes that provides a potential basis for the development of alternative pulsar detection algorithms.
PISN-explorer: hunting the descendants of very massive first stars
Authors: Aguado D S , Salvadori S , Skúladóttir Á , Caffau E , Bonifacio P , Vanni I , Gelli V , Koutsouridou I , Amarsi A M
Published: January 2023

The very massive first stars (m > 100 $\rm M_{\odot }$) were fundamental to the early phases of reionization, metal enrichment, and supermassive black hole formation. Among them, those with $140\le \rm m/\rm M_{\odot }\le 260$ are predicted to evolve as Pair Instability Supernovae (PISN) leaving a unique chemical signature in their chemical yields. Still, despite long searches, the stellar descendants of PISN remain elusive. Here we propose a new methodology, the PISN-explorer, to identify candidates for stars with a dominant PISN enrichment. The PISN-explorer is based on a combination of physically driven models, and the FERRE code; and applied to data from large spectroscopic surveys (APOGEE, GALAH, GES, MINCE, and the JINA data base). We looked into more than 1.4 million objects and built a catalogue with 166 candidates of PISN descendants. One of which, 2M13593064+3241036, was observed with UVES at VLT and full chemical signature was derived, including the killing elements, Cu and Zn. We find that our proposed methodology is efficient in selecting PISN candidates from both the Milky Way and dwarf satellite galaxies such as Sextans or Draco. Further high-resolution observations are highly required to confirm our best selected candidates, therefore allowing us to probe the existence and properties of the very massive First Stars.
Influence of fine-scale habitat characteristics on sage-grouse nest site selection and nest survival varies by mesic and xeric site conditions
Authors: Brussee Brianne E , Coates Peter S , O’Neil Shawn T , Ricca Mark A , Dudko Jonathan E , Espinosa Shawn P , Gardner Scott C , Casazza Michael L , Delehanty David J
Published: January 2023

Resource managers and scientists across western U.S. agencies seek methodologies for identifying environmental attributes important to both wildlife conservation and broad-scale land stewardship. The Greater Sage-Grouse (Centrocercus urophasianus; hereafter, sage-grouse) exemplifies a species in need of this broad-scale approach given widespread population declines that have resulted from loss and degradation of habitat from natural and anthropogenic disturbances. These include agricultural land conversion, conifer expansion, energy development, and wildfire coupled with ecological conversion by invasive plants such as cheatgrass (Bromus tectorum). Development of habitat assessments and conservation actions for sage-grouse benefit from studies that link demographic responses to habitat selection patterns. To address this, we examined nest survival of sage-grouse in relation to fine-scale habitat patterns (i.e., field-based habitat measurements) that influenced nest site selection, using data from nests of telemetered females at 17 sites over 6 years in Nevada and northeastern California, USA. Importantly, sites spanned mesic and xeric average precipitation conditions that contributed substantially to vegetation community structure across cold desert ecosystems of the North American Great Basin. Vegetative cover immediately surrounding sage-grouse nests was important for both nest site selection and nest survival, but responses varied between mesic and xeric sites. For example, while taller perennial grasses were selected at xeric sites, we found no evidence of selection for perennial grass at mesic sites, indicating a functional response to availability of habitat features between hydrographic regions. Furthermore, perennial grass height and forb height both had positive effects on nest survival at xeric sites, but we found varying effects at mesic sites. We emphasize that precipitation conditions driving ecosystem productivity vary regionally among sagebrush communities, shaping vegetation structure and suitable habitat conditions for nesting sage-grouse.
Relative Aerobic Load of Daily Activities After Stroke
Authors: Blokland Ilse J , Schiphorst Linda F A , Stroek Jessie R , Groot Floor P , van Bennekom Coen A M , van Dieen Jaap H , de Koning Jos J , Houdijk Han
Published: January 2023

Objective

Individuals after stroke are less active, experience more fatigue, and perform activities at a slower pace than peers with no impairments. These problems might be caused by an increased aerobic energy expenditure during daily tasks and a decreased aerobic capacity after stroke. The aim of this study was to quantify relative aerobic load (ie, the ratio between aerobic energy expenditure and aerobic capacity) during daily-life activities after stroke.

Methods

Seventy-nine individuals after stroke (14 in Functional Ambulation Category [FAC] 3, 25 in FAC 4, and 40 in FAC 5) and 22 peers matched for age, sex, and body mass index performed a maximal exercise test and 5 daily-life activities at a preferred pace for 5 minutes. Aerobic energy expenditure (mL O2/kg/min) and economy (mL O2/kg/unit of distance) were derived from oxygen uptake ($\dot{\mathrm{V}}{\mathrm{O}}_2$). Relative aerobic load was defined as aerobic energy expenditure divided by peak aerobic capacity (%$\dot{\mathrm{V}}{\mathrm{O}}_2$peak) and by $\dot{\mathrm{V}}{\mathrm{o}}_2$ at the ventilatory threshold (%$\dot{\mathrm{V}}{\mathrm{o}}_2$-VT) and compared in individuals after stroke and individuals with no impairments.

Results

Individuals after stroke performed activities at a significantly higher relative aerobic load (39%–82% $\dot{\mathrm{V}}{\mathrm{o}}_2$peak) than peers with no impairments (38%–66% $\dot{\mathrm{V}}{\mathrm{o}}_2$peak), despite moving at a significantly slower pace. Aerobic capacity in individuals after stroke was significantly lower than that in peers with no impairments. Movement was less economical in individuals after stroke than in peers with no impairments.

Conclusion

Individuals after stroke experience a high relative aerobic load during cyclic daily-life activities, despite adopting a slower movement pace than peers with no impairments. Perhaps individuals after stroke limit their movement pace to operate at sustainable relative aerobic load levels at the expense of pace and economy.

Impact

Improving aerobic capacity through structured aerobic training in a rehabilitation program should be further investigated as a potential intervention to improve mobility and functioning after stroke.
Mind the Gap between the Governor and the People: The Common Agency Problem in Russian Authoritarian Federalism
Authors: Klimovich Stanislav
Published: January 2023

Since the revival of direct gubernatorial elections in 2012, regional governors in Russia have two formal principals: the president and the people of the region. The principal–agent theory defines this situation as a common agency problem. In the context of authoritarian federalism, direct elections pose a two-fold challenge to Vladimir Putin’s vertical power. First, even if manipulated, elections can lead to unpredictable outcomes for the federal center. Second, in the long run, popular legitimacy incentivizes regional leaders to become more independent from the Kremlin. This study argues that the federal center in Russia has addressed the common agency problem not only by limiting the freedom of choice for the local populations through restrictive electoral law, but also by adopting a recruitment pattern that prefers outsider governors who lack personal connection to the regions of service. An original dataset on regional governors’ selection in 2012–2018 provides empirical evidence for this claim.
COVID-19 admissions and mortality in patients with early inflammatory arthritis: results from a UK national cohort
Authors: Adas Maryam A , Russell Mark D , Cook Emma , Alveyn Edward , Hannah Jennifer , Balachandran Sathiyaa , Oyebanjo Sarah , Amlani-Hatcher Paul , Ledingham Joanna , Norton Sam , Galloway James B
Published: January 2023

Objective

To describe the risks and predictors of coronavirus disease 2019 (COVID-19) hospitalization and mortality among patients with early inflammatory arthritis (EIA), recruited to the National Early Inflammatory Arthritis Audit (NEIAA).

Methods

NEIAA is an observational cohort. We included adults with EIA from Feb 2020 to May 2021. Outcomes of interest were hospitalization and death due to COVID-19, using NHS Digital linkage. Cox proportional hazards were used to calculate hazard ratios for outcomes according to initial treatment strategy, with adjustment for confounders.

Results

From 14 127 patients with EIA, there were 143 hospitalizations and 47 deaths due to COVID-19, with incidence rates per 100 person-years of 0.93 (95% CI 0.79, 1.10) for hospitalization and 0.30 (95% CI 0.23, 0.40) for death. Increasing age, male gender, comorbidities and ex-smoking were associated with increased risk of worse COVID-19 outcomes. Higher baseline DAS28 was not associated with COVID-19 admissions [confounder adjusted hazard ratio (aHR) 1.10; 95% CI 0.97, 1.24] or mortality (aHR 1.11; 95% CI 0.90, 1.37). Seropositivity was not associated with either outcome. Higher symptom burden on patient-reported measures predicted worse COVID-19 outcomes. In unadjusted models, CS associated with COVID-19 death (HR 2.29; 95% CI 1.02, 5.13), and SSZ monotherapy associated with COVID-19 admission (HR 1.92; 95% CI 1.04, 3.56). In adjusted models, associations for CS and SSZ were not statistically significant.

Conclusion

Patient characteristics have stronger associations with COVID-19 than the initial treatment strategy in patients with EIA. An important limitation is that we have not looked at treatment changes over time.
Manipulation of the Host Endomembrane System by Bacterial Effectors
Authors: Jeon Hyelim , Segonzac Cécile
Published: January 2023

The endomembrane system, extending from the nuclear envelope to the plasma membrane, is critical to the plant response to pathogen infection. Synthesis and transport of immunity-related proteins and antimicrobial compounds to and from the plasma membrane are supported by conventional and unconventional processes of secretion and internalization of vesicles, guided by the cytoskeleton networks. Although plant bacterial pathogens reside mostly in the apoplast, major structural and functional modifications of the endomembrane system in the host cell occur during bacterial infection. Here, we review the dynamics of these cellular compartments, briefly, for their essential contributions to the plant defense responses and, in parallel, for their emerging roles in bacterial pathogenicity. We further focus on Pseudomonas syringae, Xanthomonas spp., and Ralstonia solanacearum type III secreted effectors that one or both localize to and associate with components of the host endomembrane system or the cytoskeleton network to highlight the diversity of virulence strategies deployed by bacterial pathogens beyond the inhibition of the secretory pathway.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Circadian disruption impairs glucose homeostasis in male but not in female mice and is dependent on gonadal sex hormones
Authors: In het Panhuis Wietse , Schönke Milena , Siebeler Ricky , Banen Dorien , Pronk Amanda C. M. , Streefland Trea C. M. , Afkir Salwa , Sips Hetty C. M. , Kroon Jan , Rensen Patrick C. N. , Kooijman Sander
Published: January 2023

Circadian disruption (CD) is the consequence of a mismatch between endogenous circadian rhythms and behavior, and frequently occurs in shift workers. CD has often been linked to impairment of glucose and lipid homeostasis. It is, however, unknown if these effects are sex dependent. Here, we subjected male and female C57BL/6J mice to 6‐h light phase advancements every 3 days to induce CD and assessed glucose and lipid homeostasis. Within this model, we studied the involvement of gonadal sex hormones by injecting mice with gonadotropin‐releasing hormone‐antagonist degarelix. We demonstrate that CD has sex‐specific effects on glucose homeostasis, as CD elevated fasting insulin levels in male mice while increasing fasting glucose levels in female mice, which appeared to be independent of behavior, food intake, and energy expenditure. Absence of gonadal sex hormones lowered plasma insulin levels in male mice subjected to CD while it delayed glucose clearance in female mice subjected to CD. CD elevated plasma triglyceride (TG) levels and delayed plasma clearance of TG‐rich lipoproteins in both sexes, coinciding with reduced TG‐derived FA uptake by adipose tissues. Absence of gonadal sex hormones did not notably alter the effects of CD on lipid metabolism. We conclude that CD causes sex‐dependent effects on glucose metabolism, as aggravated by male gonadal sex hormones and partly rescued by female gonadal sex hormones. Future studies on CD should consider the inclusion of both sexes, which may eventually contribute to personalized advice for shift workers.
Postoperative Pulmonary Complications in the ENIGMA II Trial: A Post Hoc Analysis
Authors: Peyton Philip J. , Liskaser Grace , Ho Alexander , Marsh Harry , Etherington Christopher , Torlot Frederick , Desai Manisha , Perrett George , Chee Brian , Leslie Kate , Myles Paul S.
Published: January 2023

Background

Nitrous oxide promotes absorption atelectasis in poorly ventilated lung segments at high inspired concentrations. The Evaluation of Nitrous oxide In the Gas Mixture for Anesthesia (ENIGMA) trial found a higher incidence of postoperative pulmonary complications and wound sepsis with nitrous oxide anesthesia in major surgery compared to a fraction of inspired oxygen of 0.8 without nitrous oxide. The larger ENIGMA II trial randomized patients to nitrous oxide or air at a fraction of inspired oxygen of 0.3 but found no effect on wound infection or sepsis. However, postoperative pulmonary complications were not measured. In the current study, post hoc data were collected to determine whether atelectasis and pneumonia incidences were higher with nitrous oxide in patients who were recruited to the Australian cohort of ENIGMA II.

Methods

Digital health records of patients who participated in the trial at 10 Australian hospitals were examined blinded to trial treatment allocation. The primary endpoint was the incidence of atelectasis, defined as lung atelectasis or collapse reported on chest radiology. Pneumonia, as a secondary endpoint, required a diagnostic chest radiology report with fever, leukocytosis, or positive sputum culture. Comparison of the nitrous oxide and nitrous oxide–free groups was done according to intention to treat using chi-square tests.

Results

Data from 2,328 randomized patients were included in the final data set. The two treatment groups were similar in surgical type and duration, risk factors, and perioperative management recorded for ENIGMA II. There was a 19.3% lower incidence of atelectasis with nitrous oxide (171 of 1,169 [14.6%] vs. 210 of 1,159 [18.1%]; odds ratio, 0.77; 95% CI, 0.62 to 0.97; P = 0.023). There was no difference in pneumonia incidence (60 of 1,169 [5.1%] vs. 52 of 1159 [4.5%]; odds ratio, 1.15; 95% CI, 0.77 to 1.72; P = 0.467) or combined pulmonary complications (odds ratio, 0.84; 95% CI, 0.69 to 1.03; P = 0.093).

Conclusions

In contrast to the earlier ENIGMA trial, nitrous oxide anesthesia in the ENIGMA II trial was associated with a lower incidence of lung atelectasis, but not pneumonia, after major surgery.

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Examining the interim proposal for name change to steatotic liver disease in the US population
Authors: Ng Cheng Han , Chan Kai En , Muthiah Mark , Tan Caitlyn , Tay Phoebe , Lim Wen Hui , Tan Darren Jun Hao , Fu Clarissa Elysia , Yong Jie Ning , Wong Zhen Yu , Koh Benjamin , Chew Nicholas WS , Syn Nicholas , Huang Daniel Q. , Dan Yock Young , Siddiqui Mohammad S. , Sanyal Arun J. , Noureddin Mazen
Published: January 2023

Background and Aims:

Fatty liver is the commonest liver condition globally and traditionally associated with NAFLD. A consensus meeting was held in Chicago to explore various terminologies. Herein, we explore the proposed changes in nomenclature in a population data set from the US.

Approach and Results:

Statistical analysis was conducted using survey-weighted analysis. Assessment of fatty liver was conducted with vibration-controlled transient elastography. A controlled attenuation parameter of 288 dB/m was used to identify hepatic steatosis. Patients were classified into nonalcoholic steatotic liver disease, alcohol-associated steatotic liver disease, and viral hepatitis steatotic liver disease. Liver stiffness measures at ≥8.8, ≥11.7, and ≥14 kPa were used to identify clinically significant fibrosis, advanced fibrosis, and cirrhosis, respectively. A total of 5102 individuals were included in the analysis. Using a survey-weighted analysis, a total of 25.43%, 6.95%, and 0.73% of the population were classified as nonalcoholic steatotic liver disease, alcohol-associated steatotic liver disease, and viral hepatitis steatotic liver disease, respectively. A sensitivity analysis at controlled attenuation parameter of 248 dB/m and fatty liver index found similar distribution. In a comparison between nonalcoholic steatotic liver disease, alcohol-associated steatotic liver disease, and viral hepatitis steatotic liver disease, there was no significant difference between the odds of advanced fibrosis and cirrhosis between groups. However, viral hepatitis steatotic liver disease individuals were found to have a significantly higher odds of clinically significant fibrosis (OR: 3.76, 95% CI, 1.27–11.14, p=0.02) compared with nonalcoholic steatotic liver disease.

Conclusions:

The current analysis assessed the proposed changes based on discussions from the consensus meeting. Although the definitions are an interim analysis of discussions, steatotic liver disease respects the underlying liver etiology and reduces stigma while increasing awareness of FL among viral and alcohol-associated steatosis/steatohepatitis.