bluuebunny/crossref_metadata_2025 huggingface dataset:
Anemoside B4 alleviates arthritis pain via suppressing ferroptosis‐mediated inflammation
Authors: Guo Chenlu , Yue Yuanfen , Wang Bojun , Chen Shaohui , Li Dai , Zhen Fangshou , Liu Ling , Zhu Haili , Xie Min
Published: February 2024

Chronic pain is the key manifestations of rheumatoid arthritis. Neuroinflammation in the spinal cord drives central sensitization and chronic pain. Ferroptosis has potentially important roles in the occurrence of neuroinflammation and chronic pain. In the current study, mouse model of collagen‐induced arthritis was established by intradermal injection of type II collagen in complete Freund's adjuvant (CFA) solution. CFA inducement resulted in swollen paw and ankle, mechanical and spontaneous pain, and impaired motor coordination. The spinal inflammation was triggered, astrocytes were activated, and increased NLRP3‐mediated inflammatory signal was found in CFA spinal cord. Oxidative stress and ferroptosis in the spinal cord were manifested. Meanwhile, enhancive spinal GSK‐3β activity and abnormal phosphorylated Drp1 were observed. To investigate the potential therapeutic options for arthritic pain, mice were intraperitoneally injected with AB4 for three consecutive days. AB4 treatment reduced pain sensitivity and increased the motor coordination. In the spinal cord, AB4 treatment inhibited NLRP3 inflammasome‐mediated inflammatory response, increased antioxidation, decreased mitochondrial reactive oxygen species and ferroptosis. Furthermore, AB4 decreased GSK‐3β activity by binding with GSK‐3β through five electrovalent bonds. Our findings indicated that AB treatment relieves arthritis pain by inhibiting GSK‐3β activation, increasing antioxidant capability, reducing Drp1‐mediated mitochondrial dysfunction and suppressing neuroinflammation.
Immediately versus early placed bone‐level‐tapered implants supporting all‐ceramic crowns on titanium base abutments: 1‐year radiographic and pink esthetic outcomes of a multicenter pilot RCT
Authors: Hicklin Stefan P. , Sailer Irena , Todorovic Ana , Mojon Philippe , Worni Andreas , Strasding Malin
Published: February 2024

Objectives

Aim of this study was to assess survival rates, radiographic, and pink esthetic outcomes of a bone‐level‐tapered (BLT) implant following immediate or early implant placement.

Materials and Methods

Patients in need of tooth extraction and one implant in the anterior or premolar area were recruited in five centers. Patients were randomly assigned to the immediate or early placement protocol. Implants were restored with all‐ceramic crowns cemented to titanium‐base‐abutments. Radiographic bone levels, implant stability quotient (ISQ), and pink esthetic outcomes were assessed.

Data were analyzed descriptively. Level of significance was set at 0.05. Differences between groups were tested using Wilcoxon‐signed‐rank and Mann–Whitney‐U test as nonparametric tests.

Results

A total of 60 patients received 60 BLT implants (Institut Straumann). At 12‐months, 59 implants (98.3%) were osseointegrated. The mean distance from implant shoulder to first bone‐to‐implant contact was 0.15 ± 0.59 mm without significant differences between the groups. Median ISQ values increased from 75.5 to 78.5. A mean buccal recession of 0.1 ± 0.70 mm occurred with no difference between groups. The mean papilla height gain in both groups was 0.5 ± 1.47 mm mesially and 0.4 ± 1.36 mm distally.

Conclusions

After 1 year, immediately and early placed BLT implants exhibit similar bone level changes, ISQ values, and pink esthetic outcomes.

Clinical Significance

The present research contributes to the knowledge on clinical outcomes of immediately and early placed BLT implants restored with buccally microveneered ceramic single crowns out of two different ceramic materials. The research shows that similar esthetic and radiographic outcomes can be reached by means of immediate implant placement compared to the conventional early placement protocol. The improvement of esthetic soft‐tissue parameters over time was shown for both implant placement protocols.
Social Entrepreneurs as Ecosystem Catalysts: The Dynamics of Forming and Withdrawing from a Self‐Sustaining Ecosystem
Authors: Savaget Paulo , Ozcan Pinar , Pitsis Tyrone
Published: February 2024

Creating a long‐lasting impact is one of the defining goals of social entrepreneurship. Yet, social entrepreneurs often face a dilemma between sustaining their organization and offering a permanent fix to a social problem. We question the assumption that organizational permanence and growth are intrinsically desirable for social entrepreneurs and propose an alternative, an inductively grounded model of ecosystem leadership, which we term ecosystem catalysis. Through a single case study of social entrepreneurs addressing the lack of access to diarrhoea treatment in Zambia, we conceptualize ecosystem catalysis as a process through which an organization forms an ecosystem around a new value proposition while gradually making itself redundant, ultimately withdrawing from the ecosystem without compromising its functioning. Our work contributes to ecosystem literature by contrasting the key aims and mechanisms of an ecosystem catalyst to those of an orchestrator and identifying the conditions under which catalysing may be a better choice than orchestrating an ecosystem. We contribute to social entrepreneurship literature by decoupling social impact from organizational growth and permanence and presenting a more dynamic model of social impact resulting from distributed contributions in ecosystems.
Congregation Over Denomination: Analyzing Psychological Reactions to a Church Ruling on Same Sex Marriage
Authors: Wilkins Clara L. , Lisnek Jaclyn A. , Saadatian Kimia , Martin Lerone A.
Published: February 2024

In 2019, the United Methodist Church (UMC) voted to maintain their stance of prohibiting the ordination of gay clergy and the performance of same‐sex marriages within the church. As part of a multi‐method study, we hosted focus groups, interviews, and conducted surveys with 54 individuals from four UMC churches to assess attitudes about the outcome of the vote. Consistent with hypotheses, the majority expressed disappointment and evidence of having resolved cognitive dissonance that arose from continued church attendance. Both quantitative and qualitative measures indicated a tendency for participants to disidentify with the global church and denomination but to strengthen their commitment and ties to their more LGBTQ‐friendly local congregations. We identified themes of resilience, community, and increased activism. We discuss implications for other organizations grappling with the inclusion of sexual and gender minorities as well as implications for political polarization more broadly.
Retrospective evaluation of 22 dogs with leptospirosis treated with extracorporeal renal replacement therapies (2018‐2021)
Authors: Ioannou Antonia Da Fonseca , Tai Carolyn , Labato Mary Anna , Butty Emmanuelle M.
Published: February 2024

Background

Outcomes of dogs with acute kidney injury secondary to leptospirosis (AKI‐L) treated using renal replacement therapies (RRT) are poorly characterized.

Hypothesis/Objectives

Describe survival to discharge, short (≤30 days) and long‐term (≥6 months) outcomes of AKI‐L dogs receiving RRT and determine if there is a significant difference in maximum blood urea nitrogen (maxBUN), maximum creatinine (maxCr), maximum bilirubin (maxBili) and the number of body systems affected between survivors and non‐survivors.

Animals

Twenty‐two client‐owned dogs with AKI‐L receiving RRT.

Methods

Retrospective medical record review of dogs with AKI‐L that received RRT between 2018 and 2021.

Results

Sixteen of 22 (73%) dogs survived to discharge. Of the survivors, 13 (81%) were alive >30 days from discharge and 12 (75%) were alive at 6 months from discharge. Factors significantly higher in non‐survivors included number of body systems affected (survivors: 1 (19%), 2 (50%), 3 (25%) and 4 (6%) vs non‐survivors: 3 (33.3%), and 4 (66.7%); P = .01) and median maxBili (survivors: 1.9 mg/dL; range, 0.1‐41.6 vs non‐survivors: 21.0 mg/dL; range, 12.3‐38.9; P = .02). There was no significant difference in median maxBUN (survivors: 153.0 mg/dL; range, 67‐257 vs non‐survivors: 185.5 mg/dL; range, 102‐218; P = .44) and median maxCr (survivors: 9.8 mg/dL; range, 6.2‐15.9 vs non‐survivors: 9.8 mg/dL; range, 8.4‐13.5; P = .69) between survivors and non‐survivors.

Conclusions and Clinical Importance

Regardless of azotemia severity, dogs with AKI‐L receiving RRT have a good survival rate to discharge. The number of body systems affected and hyperbilirubinemia might be associated with worse outcomes.
Juvenile production technology for tiger shrimp, Penaeus monodon, through different stocking density using a recirculation system
Authors: Pantjara Brata , Novriadi Romi , Hendrajat Erfan A. , Herlinah Herlinah , Reynalta Ricko , Prihadi Tri H. , Kristanto Anang H. , Syah Rachman , Subagja Jojo , Widyastuti Yohanna R. , Saputra Adang , Radona Deni , Taukhid Imam
Published: February 2024

Aquaculture recirculation technology has evolved in recent years, as it can save water use and maintain good water quality during tiger shrimp fry rearing and ultimately increase juvenile production. The recirculation technology in this experiment is expected to be adopted by small‐scale tiger shrimp seed farmers. This study aims to develop the technology for producing a juvenile tiger shrimp recirculation system to support shrimp cultivation in ponds. The recirculation system container comprises a biofiltration tank filled with oysters, seaweed, and tilapia. Containers to keep tiger shrimp larvae alive in the recirculation system use a round‐shaped container with a volume of 2 m3. Tiger shrimp larvae were cared for at; A. density of 2000 individuals/m2; B. density of 1500 individuals/m2; and C. density of 1000 individuals/m2. This study found that the survival rate of tiger shrimp in treatments C and B were high, reaching 96.800b ± 2.716% and 91.62b ± 3.432%, respectively, while survival in treatment A was the lowest, at 81.700a ± 4.715%.
Exploration of cell type–specific somatic mutations in schizophrenia and the impact of maternal immune activation on the somatic mutation profile in the brain
Authors: Du Jianbin , Nakachi Yutaka , Murata Yui , Kiyota Emi , Kato Tadafumi , Bundo Miki , Iwamoto Kazuya
Published: February 2024

Aim

Schizophrenia (SZ) is a severe psychiatric disorder caused by the interaction of genetic and environmental factors. Although somatic mutations that occur in the brain after fertilization may play an important role in the cause of SZ, their frequencies and patterns in the brains of patients and related animal models have not been well studied. This study aimed to find somatic mutations related to the pathophysiology of SZ.

Methods

We performed whole‐exome sequencing (WES) of neuronal and nonneuronal nuclei isolated from the postmortem prefrontal cortex of patients with SZ (n = 10) and controls (n = 10). After detecting somatic mutations, we explored the similarities and differences in shared common mutations between two cell types and cell type–specific mutations. We also performed WES of prefrontal cortex samples from an animal model of SZ based on maternal immune activation (MIA) and explored the possible impact of MIA on the patterns of somatic mutations.

Results

We did not find quantitative differences in somatic mutations but found higher variant allele fractions of neuron‐specific mutations in patients with SZ. In the mouse model, we found a larger variation in the number of somatic mutations in the offspring of MIA mice, with the occurrence of somatic mutations in neurodevelopment‐related genes.

Conclusion

Somatic mutations occurring at an earlier stage of brain cell differentiation toward neurons may be important for the cause of SZ. MIA may affect somatic mutation profiles in the brain.
Mathematical structuralism and bundle theory
Authors: Assadian Bahram
Published: February 2024

According to the realist rendering of mathematical structuralism, mathematical structures are ontologically prior to individual mathematical objects such as numbers and sets. Mathematical objects are merely positions in structures: their nature entirely consists in having the properties arising from the structure to which they belong. In this paper, I offer a bundle‐theoretic account of this structuralist conception of mathematical objects: what we normally describe as an individual mathematical object is the mereological bundle of its structural properties. An emerging picture is a version of mereological essentialism: the structural properties of a mathematical object, as a bundle, are the mereological parts of the bundle, which are possessed by it essentially.
Consensus guidelines for nomenclature of companion animal inherited retinal disorders
Authors: Mowat Freya M. , Iwabe Simone , Aguirre Gustavo D. , Petersen‐Jones Simon M.
Published: February 2024

Companion animals, namely dogs, cats, and horses, can be affected with many forms of hereditary retinal disease. The number of such diseases characterized in the last decade has increased substantially, and nomenclature is nonstandardized, heterogenous, and confusing. We provide in this viewpoint article consensus guidelines for naming of companion animal hereditary retinal diseases, either prospectively or retrospectively. These consensus guidelines have been developed with the purpose of standardizing nomenclature. We provide examples for the iterative nomenclature process and a comprehensive File S1 on proposed renaming of previously described diseases.
Forecasting seasonal influenza activity in Canada—Comparing seasonal Auto‐Regressive integrated moving average and artificial neural network approaches for public health preparedness
Authors: Orang Armin , Berke Olaf , Poljak Zvonimir , Greer Amy L. , Rees Erin E. , Ng Victoria
Published: February 2024

Introduction

Public health preparedness is based on timely and accurate information. Time series forecasting using disease surveillance data is an important aspect of preparedness. This study compared two approaches of time series forecasting: seasonal auto‐regressive integrated moving average (SARIMA) modelling and the artificial neural network (ANN) algorithm. The goal was to model weekly seasonal influenza activity in Canada using SARIMA and compares its predictive accuracy, based on root mean square prediction error (RMSE) and mean absolute prediction error (MAE), to that of an ANN.

Methods

An initial SARIMA model was fit using automated model selection by minimizing the Akaike information criterion (AIC). Further inspection of the autocorrelation function and partial autocorrelation function led to ‘manual’ model improvements. ANNs were trained iteratively, using an automated process to minimize the RMSE and MAE.

Results

A total of 378, 462 cases of influenza was reported in Canada from the 2010–2011 influenza season to the end of the 2019–2020 influenza season, with an average yearly incidence risk of 20.02 per 100,000 population. Automated SARIMA modelling was the better method in terms of forecasting accuracy (per RMSE and MAE). However, the ANN correctly predicted the peak week of disease incidence while the other models did not.

Conclusion

Both the ANN and SARIMA models have shown to be capable tools in forecasting seasonal influenza activity in Canada. It was shown that applying both in tandem is beneficial, SARIMA better forecasted overall incidence while ANN correctly predicted the peak week.
Forward Kinematics Analysis of High-Precision Optoelectronic Packaging Platform
Authors: Wang Ziyang , Zhou Haibo , Xiao Linjiao , Duan Lian
Published: February 2024

To meet the requirements of high-precision motion control for optoelectronic packaging platforms, we propose an improved particle swarm optimization (PSO) and backpropagation (IPSO-BP) neural network for solving the forward kinematics problem (FKP) of platforms. The focus of this paper is the 6-pss flexible parallel platform commonly used in optoelectronic packaging. First, a platform inverse kinematics problem (IKP) based on a flexibility matrix is solved using geometric and vector analysis. The conventional PSO-BP network is then optimized utilizing uniform design (UD), a random learning strategy, and space reduction techniques in FKP. Finally, simulations and experiments demonstrate that the proposed IPSO-BP network for solving the FKP on high-precision optoelectronic packaging platforms is feasible. Compared to BP and PSO-BP, this network has a higher resolution, faster convergence speed, and error control at the submicron level, which satisfies the motion control requirements of the platform at the micron level. This study lays a solid foundation for the production of high-quality devices in optoelectronic packaging.
Heat Transfer and Flow Characteristics of Channel Impingement Cooling Structure at Leading Edge Inside Turbine Blades Using Large Eddy Simulation
Authors: Wang Huihui , Deng Qinghua , Feng Zhenping
Published: February 2024

As a main part of multichannel wall jet cooling structure, channel impingement cooling is a cooling strategy of great concern at the leading edge inside of the turbine blade. In this paper, heat transfer and flow behavior in the channel impingement cooling structure are investigated by large eddy simulation (LES). The results imply that impingement created by curvature-induced centrifugal instabilities in the turning region of the cooling channel is dominated by a streamwise vortex system containing a counter-rotating Dean vortex, which presents high heat transfer streaks along the streamwise direction on the target wall. The intensely unsteady nature of the cooling jet induced by a lack of equilibrium between the pressure gradient and the centrifugal force is precisely captured herein by LES. An attaching-wall jet formed on the outer wall downstream of the cooling channel has highly three-dimensional characteristics not observed by Reynolds-averaged Navier–Stokes equations (RANS). Heat transfer augmentation on the target wall of the cooling channel is mainly due to the intensifying streamwise vortex system developing in the turning region as driven by the centrifugal force. This research work will provide a reference for the optimization and application of multichannel wall jet cooling for gas turbine blades.
Integrated Wheel–Foot–Arm Design of a Mobile Platform With Linkage Mechanisms
Authors: Du Yuting , Ruan Qiang , Yao Yan-an
Published: February 2024

Inspired by lizards, a novel mobile platform with revolving linkage legs is proposed. The platform consists of four six-bar bipedal modules, and it is designed for heavy transportation on unstructured terrain. The platform possesses smooth-wheeled locomotion and obstacle-adaptive legged locomotion to enhance maneuverability. The kinematics of the six-bar bipedal modules is analyzed using the vector loop method, subsequently ascertaining the drive scheme. The foot trajectory compensation curve is generated using the fixed-axis rotation contour algorithm, which effectively reduces the centroid fluctuation and enables seamless switching between wheels and legs. When encountering obstacles, the revolving linkage legs act as climbing arms, facilitating seamless integration of wheel, foot, and arm. A physical prototype is developed to test the platform on three typical terrains: flat terrain, slope, and vertical obstacle. The experimental results demonstrated the feasibility of the platform structure. The platform can climb obstacles higher than its own height without adding extra actuation.
Advancing Legged Wall Climbing Robot Performance Through Dynamic Contact-Integrated Climbing Model
Authors: Fang Shengchang , Chen Guisong , Zhou Yitong , Wang Xiaojie
Published: February 2024

Climbing robots have gained significance in hazardous and steep terrains, yet adapting to complex environments remains a challenge. Inspired by nature's climbers, this paper introduces a climbing dynamics model that integrates foot-end contact forces, crucial for safe and efficient wall climbing. Drawing insights from animal locomotion and biomechanics, we present a comprehensive dynamic model for quadruped robots. Our model, built upon multibody dynamics and a dynamic contact model based on spiny claw mechanisms, accurately simulates robot forces and motion during climbing, even predicting failure scenarios. Experimental validation further establishes model accuracy. This study advances climbing robot research by addressing attachment interaction dynamics and provides valuable insights for optimizing robot structural design and gait strategies.
Real-time, noise and drift resilient formaldehyde sensing at room temperature with aerogel filaments
Authors: Chen Zhuo , Zhou Binghan , Xiao Mingfei , Bhowmick Tynee , Karthick Kannan Padmanathan , Occhipinti Luigi G. , Gardner Julian William , Hasan Tawfique
Published: February 2024

Formaldehyde, a known human carcinogen, is a common indoor air pollutant. However, its real-time and selective recognition from interfering gases remains challenging, especially for low-power sensors suffering from noise and baseline drift. We report a fully 3D-printed quantum dot/graphene-based aerogel sensor for highly sensitive and real-time recognition of formaldehyde at room temperature. By optimizing the morphology and doping of printed structures, we achieve a record-high and stable response of 15.23% for 1 part per million formaldehyde and an ultralow detection limit of 8.02 parts per billion consuming only ∼130-microwatt power. On the basis of measured dynamic response snapshots, we also develop intelligent computational algorithms for robust and accurate detection in real time despite simulated substantial noise and baseline drift, hitherto unachievable for room temperature sensors. Our framework in combining materials engineering, structural design, and computational algorithm to capture dynamic response offers unprecedented real-time identification capabilities of formaldehyde and other volatile organic compounds at room temperature.
Mucosal and systemic immune correlates of viral control after SARS-CoV-2 infection challenge in seronegative adults
Authors: Wagstaffe Helen R. , Thwaites Ryan S. , Reynaldi Arnold , Sidhu Jasmin K. , McKendry Richard , Ascough Stephanie , Papargyris Loukas , Collins Ashley M. , Xu Jiayun , Lemm Nana-Marie , Siggins Matthew K. , Chain Benny M. , Killingley Ben , Kalinova Mariya , Mann Alex , Catchpole Andrew , Davenport Miles P. , Openshaw Peter J. M. , Chiu Christopher
Published: February 2024

Human infection challenge permits in-depth, early, and pre-symptomatic characterization of the immune response, enabling the identification of factors that are important for viral clearance. Here, we performed intranasal inoculation of 34 young adult, seronegative volunteers with a pre-Alpha severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. Of these participants, 18 (53%) became infected and showed an interferon-dominated mediator response with divergent kinetics between nasal and systemic sites. Peripheral CD4
+
and CD8
+
T cell activation and proliferation were early and robust but showed distinct kinetic and phenotypic profiles; antigen-specific T cells were largely CD38
+
Ki67
+
and displayed central and effector memory phenotypes. Both mucosal and systemic antibodies became detectable around day 10, but nasal antibodies plateaued after day 14 while circulating antibodies continued to rise. Intensively granular measurements in nasal mucosa and blood allowed modeling of immune responses to primary SARS-CoV-2 infection that revealed CD8
+
T cell responses and early mucosal IgA responses strongly associated with viral control, indicating that these mechanisms should be targeted for transmission-reducing intervention.
Culture-independent detection of low-abundant
Clostridioides difficile
in environmental DNA via PCR
Authors: Schüler Miriam A. , Schneider Dominik , Poehlein Anja , Daniel Rolf
Published: February 2024

Clostridioides difficile
is a main cause of diarrheic infections after antibiotic treatment with serious morbidity and mortality worldwide. Research on this pathogen and its virulence has focused on bacterial isolation from clinical specimens under antibiotic treatment, which implies a substantial bias in isolated strains. Comprehensive studies, however, require an unbiased strain collection, which is accomplished by isolation of
C. difficile
from diverse environmental samples and avoidance of antibiotic-based enrichment strategies. Thus, isolation can significantly benefit from our
C. difficile
-specific detection PCR, which rapidly verifies
C. difficile
presence in environmental samples and further allows estimation of the
C. difficile
diversity by using next-generation sequencing.
Genomic epidemiology of third-generation cephalosporin-resistant
Escherichia coli
from Argentinian pig and dairy farms reveals animal-specific patterns of co-resistance and resistance mechanisms
Authors: Mounsey Oliver , Marchetti Laura , Parada Julián , Alarcón Laura V. , Aliverti Florencia , Avison Matthew B. , Ayala Carlos S. , Ballesteros Cristina , Best Caroline M. , Bettridge Judy , Buchamer Andrea , Buldain Daniel , Carranza Alicia , Corti Isgro Maite , Demeritt David , Escobar Maria Paula , Gortari Castillo Lihuel , Jaureguiberry María , Lucas Mariana F. , Madoz L. Vanina , Marconi María José , Moiso Nicolás , Nievas Hernán D. , Ramirez Montes De Oca Marco A. , Reding Carlos , Reyher Kristen K. , Vass Lucy , Williams Sara , Giraudo José , De La Sota R. Luzbel , Mestorino Nora , Moredo Fabiana A. , Pellegrino Matías
Published: February 2024

Little is known about the ecology of critically important antibiotic resistance among bacteria with the potential to be opportunistic human pathogens (e.g.,
Escherichia coli
) on South American farms. By studying 70 pig and dairy cattle farms in central-eastern Argentina, we identified that third-generation cephalosporin resistance (3GC-R) in
E. coli
was mediated by mechanisms seen more often in certain species and that 3GC-R pig
E. coli
were more likely to be co-resistant to florfenicol and amoxicillin/clavulanate. This suggests that on-farm antibiotic usage is key to selecting the types of
E. coli
present on these farms. 3GC-R
E. coli
and 3GC-R plasmids were diverse, suggestive of long-term circulation in this region. We identified the
de novo
mobilization of the resistance gene

bla
ROB

from pig pathogens into
E. coli
on a novel mobile genetic element, which shows the importance of surveying poorly studied regions for antibiotic resistance that might impact human health.
Comparative genomic analysis of symbiotic and free-living
Fluviibacter phosphoraccumulans
strains provides insights into the evolutionary origins of obligate
Euplotes
–bacterial endosymbioses
Authors: Wang Ruanlin , Meng Qingyao , Wang Xue , Xiao Yu , Sun Ruijuan , Zhang Zhiyun , Fu Yuejun , Di Giuseppe Graziano , Liang Aihua
Published: February 2024

In the long history of symbiosis research, most studies focused mainly on organelles or bacteria within multicellular hosts. The single-celled protists receive little attention despite harboring an immense diversity of symbiotic associations with bacteria and archaea. One subgroup of the ciliate
Euplotes
species is strictly dependent on essential symbionts for survival and has emerged as a valuable model for understanding symbiont replacements and recent symbioses. However, almost all of our knowledge about the evolution and functions of
Euplotes
symbioses comes from the
Euplotes
–
Polynucleobacter
system. In this article, we report a novel essential symbiont, which also has very close free-living relatives. Genome analysis indicated that it is a recently established endosymbiont undergoing genome erosion and relies on the
Euplotes
host for many essential molecules. Our results provide support for the notion that essential symbionts of the ciliate
Euplotes
evolve from free-living progenitors in the natural water environment.
Brine formation in cold desert, shallow groundwater systems: Antarctic Ca-Cl brine chemistry controlled by cation exchange, microclimate, and organic matter
Authors: King I.C. , Johnson J.T.E. , Kuang L. , Naylor S. , Subak T. , Koleszar A.M. , Levy J.S.
Published: February 2024

Groundwater in the McMurdo Dry Valleys of Antarctica is commonly enriched in calcium and chloride, in contrast to surface and groundwater in temperate regions, where calcium chemistry is largely controlled by the dissolution of carbonates and sulfates. These Antarctic Ca-Cl brines have extremely low freezing points, which leads to moist soil conditions that persist unfrozen and resist evaporation, even in cold, arid conditions. Several hypotheses exist to explain these unusual excess-calcium solutions, including salt deliquescence and differential salt mobility and cation exchange. Although the cation exchange mechanism was shown to explain the chemistry of pore waters in permafrost cores from several meters depth, it has not been evaluated for near-surface groundwater and wetland features (water tracks) in which excess-calcium pore-water solutions are common. Here, we use soluble salt and exchangeable cation concentrations to determine whether excess calcium is present in water-track brines and if cation exchange could be responsible for calcium enrichment in these cold desert groundwaters. We show that calcium enrichment by cation exchange is not occurring universally across the McMurdo Dry Valleys. Instead, evidence of the present-day formation of Ca-Cl–rich brines by cation exchange is focused in a geographically specific location in Taylor Valley, with hydrological position, microclimate, soil depth, and organic matter influencing the spatial extent of cation exchange reactions. Up-valley sites may be too cold and dry for widespread exchange, and warm and wet coastal sites are interpreted to host sediments whose exchange reactions have already gone to completion. We argue that exchangeable cation ratios can be used as a signature of past freeze-concentration of brines and exchange reactions, and thus could be considered a geochemical proxy for past groundwater presence in planetary permafrost settings. Correlations between water-track organic matter, fine sediment concentration, and cation exchange capacity suggest that water tracks may be sites of enhanced biogeochemical cycling in cold desert soils and serve as a model for predicting how active layers in the Antarctic will participate in biogeochemical cycling during periods of future thaw.
Copper skarn mineralization related to reduced monzodioritic magma at the Huanren deposit, northeastern China
Authors: Ouyang Hegen , Caulfield John , Xie Guiqing , Duan Chao , Mao Jingwen , Li Xin
Published: February 2024

Most known copper (Cu) skarns are associated with oxidized intrusions. In this contribution, we report a Cu skarn associated with a reduced monzodioritic intrusion at Huanren, northeastern China, which contains 0.41 Mt of Cu accompanied by economic concentrations of Zn, Pb, Fe, Mo, and Ag. Copper-polymetallic mineralization in the Huanren deposit is concentrated in skarns located between the contacts of the monzodiorite (SiO2 = 52–55 wt%) and the Cambrian carbonate rocks, with minor molybdenite-bearing veinlets/veins and dissimilated chalcopyrite mineralization hosted within the monzodiorite. Laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) U-Pb zircon geochronology indicates the monzodiorite crystallized at 125.4 ± 0.6 Ma (2σ). Isotope dilution (ID)-ICP-MS Re-Os molybdenite geochronology indicates mineralization at Huanren occurred at 125.3 ± 0.8 Ma (2σ). Whole-rock major- and trace-element and zircon Hf isotopic compositions suggest enriched (subduction metasomatized) lithospheric mantle–derived sources for the parental magma of the monzodiorite without significant crustal assimilation. Zircon trace-element and magmatic apatite major-element compositions indicate the reduced nature of the monzodiorite, as evidenced by low magmatic oxygen fugacity (fayalite-magnetite-quartz [FMQ] buffer = −1.09 ± 0.19) and negligible apatite SO3 contents (<0.05 wt%). A reduced magmatic-hydrothermal system at Huanren is also supported by the predominance of magmatic ilmenite over magnetite in the monzodiorite and by the presence of pyrrhotite and the absence of anhydrite and hematite in the ore. Chalcopyrite from the Huanren deposit has an average δ34S value of 4.34‰ ± 0.88‰ (1σ), which is clearly higher than values from most porphyry-skarn Cu ± Mo ± Au deposits. Accordingly, we suggest that interaction between (1) external oxidized fluids equilibrated with evaporites and (2) reduced Cl-bearing magmas and related exsolved fluids may have played a critical role in the formation of the Huanren Cu skarn by increasing the ability of fluids to scavenge Cu from the reduced magma and subsequently precipitate Cu in the carbonate rocks. This study defines a new type of Cu skarn and thereby opens new potential for Cu skarn exploration proximal to intrusive units previously deemed too reduced to be Cu fertile, especially in non-arc settings. Moreover, we conclude that the availability of Cl and S in magmatic-hydrothermal systems may be as critical as fO2 in facilitating the actual ore-forming event in Cu skarn systems.
Geoelectric evidence for a wide spatial footprint of active extension in central Colorado
Authors: Murphy Benjamin S. , Caine Jonathan Saul , Bedrosian Paul A. , Crosbie Jade W.
Published: February 2024

Three-dimensional magnetotelluric (MT) imaging in central Colorado reveals a set of north-striking high-conductivity tracks at lower-crustal (50–20 km) depths, with conductive finger-like structures rising off these tracks into the middle crust (20–5 km depth). We interpret these features to represent saline aqueous fluids and partial melt that are products of active extensional tectonomagmatism. These conductors are distributed over a wider region than the narrow corridor along which Rio Grande rift structures are traditionally mapped at the surface, and they consequently demarcate regions of the lower crust where accommodation of bulk extensional strain has concentrated conductive phases. Our observations reveal limitations in existing models of Rio Grande rift activity and may reflect unrecognized spatiotemporal variations in rift system evolution globally.
Randomised study of a new inline respiratory function monitor (Juno) to improve mask seal and delivered ventilation with neonatal manikins
Authors: Tracy Mark Brian , Hinder Murray , Morakeas Stephanie , Lowe Krista , Priyadarshi Archana , Crott Matthew , Boustred Matthew , Culcer Mihaela
Published: February 2024

Background

Respiratory function monitors (RFMs) have been used extensively in manikin and infant studies yet have not become the standard of training. We report the outcomes of a new portable, lightweight RFM, the Juno, designed to show mask leak and deflation tidal volume to assist in positive pressure ventilation (PPV) competency training using manikins.

Methods

Two leak-free manikins (preterm and term) were used. Participants provided PPV to manikins using two randomised devices, self-inflating bag (SIB) and T-piece resuscitator (TPR), with Juno display initially blinded then unblinded in four 90 s paired sequences, aiming for adequate chest wall rise and target minimal mask leak with appropriate target delivered volume when using the monitor.

Results

49 experienced neonatal staff delivered 15 569 inflations to the term manikin and 14 580 inflations to the preterm. Comparing blinded to unblinded RFM display, there were significant reductions in all groups in the number of inflations out of target range volumes (preterm: SIB 22.6–6.6%, TPR 7.1–4.2% and term: SIB 54.8–37.8%, TPR 67.2–63.8%). The percentage of mask leak inflations >60% was reduced in preterm: SIB 20.7–7.2%, TPR 23.4–7.4% and in term: SIB 8.7–3.6%, TPR 23.5–6.2%).

Conclusions

Using the Juno monitor during simulated resuscitation significantly improved mask leak and delivered ventilation among otherwise experienced staff using preterm and term manikins. The Juno is a novel RFM that may assist in teaching and self-assessment of resuscitation PPV technique.
Bladder cancer intrinsic LRFN2 drives anticancer immunotherapy resistance by attenuating CD8+T cell infiltration and functional transition
Authors: Yu Anze , Hu Jiao , Fu Liangmin , Huang Gaowei , Deng Dingshan , Zhang Mingxiao , Wang Yinghan , Shu Guannan , Jing Lanyu , Li Huihuang , Chen Xu , Yang Taowei , Wei Jinhuan , Chen Zhenhua , Zu Xiongbing , Luo Junhang
Published: February 2024

Background

Immune checkpoint inhibitor (ICI) therapy improves the survival of patients with advanced bladder cancer (BLCA); however, its overall effectiveness is limited, and many patients still develop immunotherapy resistance. The leucine-rich repeat and fibronectin type-III domain-containing protein (LRFN) family has previously been implicated in regulating brain dysfunction; however, the mechanisms underlying the effect of LRFN2 on the tumor microenvironment (TME) and immunotherapy remain unclear.

Methods

Here we combined bulk RNA sequencing, single-cell RNA sequencing, ProcartaPlex multiple immunoassays, functional experiments, and TissueFAXS panoramic tissue quantification assays to demonstrate that LRFN2 shapes a non-inflammatory TME in BLCA.

Results

First, comprehensive multiomics analysis identified LRFN2 as a novel immunosuppressive target specific to BLCA. We found that tumor-intrinsic LRFN2 inhibited the recruitment and functional transition of CD8+T cells by reducing the secretion of pro-inflammatory cytokines and chemokines, and this mechanism was verified in vitro and in vivo. LRFN2 restrained antitumor immunity by inhibiting the infiltration, proliferation, and differentiation of CD8+T cells in vitro. Furthermore, a spatial exclusivity relationship was observed between LRFN2+tumor cells and CD8+T cells and cell markers programmed cell death-1 (PD-1) and T cell factor 1 (TCF-1). Preclinically, LRFN2 knockdown significantly enhanced the efficacy of ICI therapy. Clinically, LRFN2 can predict immunotherapy responses in real-world and public immunotherapy cohorts. Our results reveal a new role for LRFN2 in tumor immune evasion by regulating chemokine secretion and inhibiting CD8+T-cell recruitment and functional transition.

Conclusions

Thus, LRFN2 represents a new target that can be combined with ICIs to provide a potential treatment option for BLCA.
Seroreactivity against lytic, latent and possible cross-reactive EBV antigens appears on average 10 years before MS induced preclinical neuroaxonal damage
Authors: Jons Daniel , Grut Viktor , Bergström Tomas , Zetterberg Henrik , Biström Martin , Gunnarsson Martin , Vrethem Magnus , Brenner Nicole , Butt Julia , Blennow Kaj , Nilsson Staffan , Kockum Ingrid , Olsson Tomas , Waterboer Tim , Sundström Peter , Andersen Oluf
Published: February 2024

Background

Multiple sclerosis (MS) and presymptomatic axonal injury appear to develop only after an Epstein-Barr virus (EBV) infection. This association remains to be confirmed across a broad preclinical time range, for lytic and latent EBV seroreactivity, and for potential cross-reacting antigens.

Methods

We performed a case–control study with 669 individual serum samples obtained before clinical MS onset, identified through cross-linkage with the Swedish MS register. We assayed antibodies against EBV nuclear antigen 1 (EBNA1), viral capsid antigen p18, glycoprotein 350 (gp350), the potential cross-reacting protein anoctamin 2 (ANO2) and the level of sNfL, a marker of axonal injury.

Results

EBNA1 (latency) seroreactivity increased in the pre-MS group, at 15–20 years before clinical MS onset, followed by gp350 (lytic) seroreactivity (p=0.001–0.009), ANO2 seropositivity appeared shortly after EBNA1-seropositivity in 16.7% of pre-MS cases and 10.0% of controls (p=0.001).With an average lag of almost a decade after EBV, sNfL gradually increased, mainly in the increasing subgroup of seropositive pre-MS cases (p=8.10−5compared with non-MS controls). Seropositive pre-MS cases reached higher sNfL levels than seronegative pre-MS (p=0.038). In the EBNA1-seropositive pre-MS group, ANO2 seropositive cases had 26% higher sNfL level (p=0.0026).

Conclusions

Seroreactivity against latent and lytic EBV antigens, and in a subset ANO2, was detectable on average a decade before the appearance of a gradually increasing axonal injury occurring in the last decade before the onset of clinical MS. These findings strengthen the hypothesis of latent EBV involvement in the pathogenesis of MS.
High-dimensional analysis of T-cell profiling variations following belimumab treatment in systemic lupus erythematosus
Authors: Maeda Shinji , Hashimoto Hiroya , Maeda Tomoyo , Tamechika Shin-ya , Isogai Shuntaro , Naniwa Taio , Niimi Akio
Published: February 2024

Objective

This study sought to elucidate the molecular impacts of belimumab (BEL) treatment on T-cell immune profiling in SLE.

Methods

We used mass cytometry with 25 marker panels for T-cell immune profiling in peripheral blood T cells (CD3+) from 22 patients with BEL-treated SLE and 20 controls with non-BEL-treated SLE. An unsupervised machine-learning clustering, FlowSOM, was used to identify 39 T-cell clusters (TCLs; TCL01–TCL39). TCLs (% of CD3+) showing significant (p<0.05) associations with BEL treatment (BEL-TCL) were selected by a linear mixed-effects model for comparing groups of time-series data. Furthermore, we analysed the association between BEL treatment and variations in regulatory T-cell (Treg) phenotypes, and the ratio of other T-cell subsets to Treg as secondary analysis.

Results

Clinical outcomes: BEL treatment was associated with a decrease in daily prednisolone use (coef=−0.1769, p=0.00074), and an increase in serum CH50 (coef=0.4653, p=0.003), C3 (coef=1.1047, p=0.00001) and C4 (coef=0.2990, p=0.00157) levels. Molecular effects: five distinct BEL-TCLs (TCL 04, 07, 11, 12 and 27) were identified. Among these, BEL-treated patients exhibited increased proportions in the Treg-like cluster TCL11 (coef=0.404, p=0.037) and two naïve TCLs (TCL04 and TCL07). TCL27 showed increased levels (coef=0.222, p=0.037) inversely correlating with baseline C3 levels. Secondary analyses revealed associations between BEL treatment and an increase in Tregs (coef=1.749, p=0.0044), elevated proportions of the fraction of Tregs with inhibitory function (fTregs, coef=0.7294, p=0.0178) and changes in peripheral helper T cells/fTreg (coef=−4.475, p=0.0319) and T helper 17/fTreg ratios (coef=−6.7868, p=0.0327). Additionally, BEL was linked to variations in T-cell immunoglobulin and mucin domain-containing protein-3 expression (coef=0.2422, p=0.039).

Conclusions

The study suggests an association between BEL treatment and variations in T cells, particularly Tregs, in SLE pathologies involving various immune cells.
Prediction of futile recanalisation after endovascular treatment in acute ischaemic stroke: development and validation of a hybrid machine learning model
Authors: Nie Ximing , Yang Jinxu , Li Xinxin , Zhan Tianming , Liu Dongdong , Yan Hongyi , Wei Yufei , Liu Xiran , Chen Jiaping , Gong Guoyang , Wu Zhenzhou , Yang Zhonghua , Wen Miao , Gu Weibin , Pan Yuesong , Jiang Yong , Meng Xia , Liu Tao , Cheng Jian , Li Zixiao , Miao Zhongrong , Liu Liping
Published: February 2024

Background

Identification of futile recanalisation following endovascular therapy (EVT) in patients with acute ischaemic stroke is both crucial and challenging. Here, we present a novel risk stratification system based on hybrid machine learning method for predicting futile recanalisation.

Methods

Hybrid machine learning models were developed to address six clinical scenarios within the EVT and perioperative management workflow. These models were trained on a prospective database using hybrid feature selection technique to predict futile recanalisation following EVT. The optimal model was validated and compared with existing models and scoring systems in a multicentre prospective cohort to develop a hybrid machine learning-based risk stratification system for futile recanalisation prediction.

Results

Using a hybrid feature selection approach, we trained and tested multiple classifiers on two independent patient cohorts (n=1122) to develop a hybrid machine learning-based prediction model. The model demonstrated superior discriminative ability compared with other models and scoring systems (area under the curve=0.80, 95% CI 0.73 to 0.87) and was transformed into a web application (RESCUE-FR Index) that provides a risk stratification system for individual prediction (accessible online at fr-index.biomind.cn/RESCUE-FR/).

Conclusions

The proposed hybrid machine learning approach could be used as an individualised risk prediction model to facilitate adherence to clinical practice guidelines and shared decision-making for optimal candidate selection and prognosis assessment in patients undergoing EVT.
Intracerebral haemorrhage in patients taking different types of oral anticoagulants: a pooled individual patient data analysis from two national stroke registries
Authors: Siepen Bernhard M , Forfang Elisabeth , Branca Mattia , Drop Boudewijn , Mueller Madlaine , Goeldlin Martina B , Katan Mira , Michel Patrik , Cereda Carlo , Medlin Friedrich , Peters Nils , Renaud Susanne , Niederhauser Julien , Carrera Emmanuel , Kahles Timo , Kägi Georg , Bolognese Manuel , Salmen Stephan , Mono Marie-Luise , Polymeris Alexandros A , Wegener Susanne , Z'Graggen Werner , Kaesmacher Johannes , Schaerer Michael , Rodic Biljana , Kristoffersen Espen Saxhaug , Larsen Kristin T , Wyller Torgeir Bruun , Volbers Bastian , Meinel Thomas R , Arnold Marcel , Engelter Stefan T , Bonati Leo H , Fischer Urs , Rønning Ole Morten , Seiffge David J
Published: February 2024

Background

We investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation.

Methods

This is an individual patient data study combining two prospective national stroke registries from Switzerland and Norway (2013–2019). We included all consecutive patients with ICH from both registries. The main outcomes were favourable functional outcome (modified Rankin Scale 0–2) and mortality at 3 months.

Results

Among 11 349 patients with ICH (mean age 73.6 years; 47.6% women), 1491 (13.1%) were taking VKAs and 1205 (10.6%) DOACs (95.2% factor Xa inhibitors). The median percentage of patients on prior anticoagulation was 23.7 (IQR 22.6–25.1) with VKAs decreasing (from 18.3% to 7.6%) and DOACs increasing (from 3.0% to 18.0%) over time. Prior VKA therapy (n=209 (22.3%); adjusted ORs (aOR), 0.64; 95% CI, 0.49 to 0.84) and prior DOAC therapy (n=184 (25.7%); aOR, 0.64; 95% CI, 0.47 to 0.87) were independently associated with lower odds of favourable outcome compared with patients without anticoagulation (n=2037 (38.8%)). Prior VKA therapy (n=720 (49.4%); aOR, 1.71; 95% CI, 1.41 to 2.08) and prior DOAC therapy (n=460 (39.7%); aOR, 1.28; 95% CI, 1.02 to 1.60) were independently associated with higher odds of mortality compared with patients without anticoagulation (n=2512 (30.2%)).

Conclusions

The spectrum of anticoagulation-associated ICH changed over time. Compared with patients without prior anticoagulation, prior VKA treatment and prior DOAC treatment were independently associated with lower odds of favourable outcome and higher odds of mortality at 3 months. Specific reversal agents unavailable during the study period might improve outcomes of DOAC-associated ICH in the future.