bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipids and Phosphorylation Conjointly Modulate Complex Formation of β2-Adrenergic Receptor and β-arrestin2
Authors: Pluhackova Kristyna , Wilhelm Florian M. , Müller Daniel J.
Published: December 2021

G protein-coupled receptors (GPCRs) are the largest class of human membrane proteins that bind extracellular ligands at their orthosteric binding pocket to transmit signals to the cell interior. Ligand binding evokes conformational changes in GPCRs that trigger the binding of intracellular interaction partners (G proteins, G protein kinases, and arrestins), which initiate diverse cellular responses. It has become increasingly evident that the preference of a GPCR for a certain intracellular interaction partner is modulated by a diverse range of factors, e.g., ligands or lipids embedding the transmembrane receptor. Here, by means of molecular dynamics simulations of the β2-adrenergic receptor and β-arrestin2, we study how membrane lipids and receptor phosphorylation regulate GPCR-arrestin complex conformation and dynamics. We find that phosphorylation drives the receptor’s intracellular loop 3 (ICL3) away from a native negatively charged membrane surface to interact with arrestin. If the receptor is embedded in a neutral membrane, the phosphorylated ICL3 attaches to the membrane surface, which widely opens the receptor core. This opening, which is similar to the opening in the G protein-bound state, weakens the binding of arrestin. The loss of binding specificity is manifested by shallower arrestin insertion into the receptor core and higher dynamics of the receptor-arrestin complex. Our results show that receptor phosphorylation and the local membrane composition cooperatively fine-tune GPCR-mediated signal transduction. Moreover, the results suggest that deeper understanding of complex GPCR regulation mechanisms is necessary to discover novel pathways of pharmacological intervention.
Comprehensive Analysis Revealed that CDKN2A is a Biomarker for Immune Infiltrates in Multiple Cancers
Authors: Chen Zheng , Guo Yingjie , Zhao Da , Zou Quan , Yu Fusheng , Zhang Lijun , Xu Lei
Published: December 2021

The CDKN2A (cyclin dependent kinase inhibitor 2A/multiple tumor suppressor 1) gene, also known as the P16 gene, encodes multiple tumor suppressor 1 (MTS1), which belongs to the INK4 family. In tumor tissue, CDKN2A has a high expression level compared with normal tissue and reflects prognosis in tumor patients. Our research targeted the analysis of CDKN2A expression in 33 tumors and clinical parameters, patient prognosis and tumor immunity roles. The CDKN2A expression level was significantly correlated with the tumor mutation burden (TMB) in 10 tumors, and the expression of CDKN2A was also correlated with MSI (microsatellite instability) in 10 tumors. CDKN2A expression was associated with infiltrating lymphocyte (TIL) levels in 22 pancancers, thus suggesting that CDKN2A expression is associated with tumor immunity. Enrichment analysis indicated that CDKN2A expression was involved in natural killer cell-mediated cytotoxicity pathways, antigen processing and presentation, olfactory transduction pathways, and regulation of the autophagy pathway in multiple cancers. CDKN2A was significantly associated with several immune cell infiltrates in pantumors. CDKN2A may serve as a promising prognostic biomarker and is associated with immune infiltrates across cancers.
Electrochemical Bromination of Glycals
Authors: Luo Zhao-Xiang , Liu Miao , Li Tian , Xiong De-Cai , Ye Xin-Shan
Published: December 2021

Herein, the convenient one-step electrochemical bromination of glycals using Bu4NBr as the brominating source under metal-catalyst-free and oxidant-free reaction conditions was described. A series of 2-bromoglycals bearing different electron-withdrawing or electron-donating protective groups were successfully synthesized in moderate to excellent yields. The coupling of tri-O-benzyl-2-bromogalactal with phenylacetylene, potassium phenyltrifluoroborate, or a 6-OH acceptor was achieved to afford 2C-branched carbohydrates and disaccharides via Sonogashira coupling, Suzuki coupling, and Ferrier rearrangement reactions with high efficiency. The radical trapping and cyclic voltammetry experiments indicated that bromine radicals may be involved in the reaction process.
Catalytic Scenarios Over Metal-Carbon Interaction Interface
Authors: Xing Liwen , Jin Yujuan , Weng Yunxuan , Ji Yongjun
Published: December 2021

Numerous efforts have been devoted to investigating the catalytic events and disclosing the catalytic nature of the metal-carbon interaction interface. Nevertheless, the local deconstruction of catalytically active metal-carbon interface was still missing. Herein, the selected four types of landmark catalytic paradigms were highlighted, which was expected to clarify their essence and thus simplify the catalytic scenarios of the metal-carbon interface—carbon-supported metal nanoparticles, carbon-confined single-atom sites, chainmail catalysis, and the Mott-Schottky effect. The potential challenges and new opportunities were also proposed in the field. This perspective is believed to give an in-depth understanding of the catalytic nature of the metal-carbon interaction interface and in turn provide rational guidance to the delicate design of novel high-performance carbon-supported metal catalysts.
Teaching Students How to Frame Human-Computer Interactions Using Instrumentalism, Technological Determinism, and a Quadrant Learning Activity
Authors: Fernandez Luke
Published: December 2021

This paper describes an innovative learning activity for educating students about human-computer interaction. The goal of this learning activity is to familiarize students with the way instrumentalists on the one hand, and technological determinists on the other, conceive of human-technology interaction, and to assess which theory students favor. This paper describes and evaluates the efficacy of this learning activity and presents preliminary data on student responses. It also establishes a framework for understanding how students initially perceive human-technology interaction and how that understanding can be used to personalize and improve their learning. Instrumentalists believe that technology can be understood simply as a tool or neutral instrument that humans use to achieve their own ends. In contrast, technological determinists believe that technology is not fully under human control, that it has some degree of autonomy, and that it has its own ends. Exposing students to these two theories of human-technological interaction provides five benefits: First, the competing theories deepen students’ ability to describe how technology and humans interact. Second, they provide an ethical framework that students can use to describe how technology and humans should interact. Third, they provide students with a vocabulary that they can use to talk about human freedom and how the design of computing technology may constrain or expand that freedom. Fourth, by challenging students to articulate what theory they favor, the learning is personalized. Fifth, because the learning activity challenges students to express their personal beliefs about how humans and technology interact, the learning activity can help instructors develop a clearer understanding of those beliefs and whether they reinforce what Erin Cech has identified as a culture of depoliticization and disengagement in engineering culture.
Vascular Dementia and Crosstalk Between the Complement and Coagulation Systems
Authors: Mossanen Parsi Milad , Duval Cédric , Ariëns Robert A. S.
Published: December 2021

Vascular Dementia (VaD) is a neurocognitive disorder caused by reduced blood flow to the brain tissue, resulting in infarction, and is the second most common type of dementia. The complement and coagulation systems are evolutionary host defence mechanisms activated by acute tissue injury to induce inflammation, clot formation and lysis; recent studies have revealed that these systems are closely interlinked. Overactivation of these systems has been recognised to play a key role in the pathogenesis of neurological disorders such as Alzheimer's disease and multiple sclerosis, however their role in VaD has not yet been extensively reviewed. This review aims to bridge the gap in knowledge by collating current understanding of VaD to enable identification of complement and coagulation components involved in the pathogenesis of this disorder that may have their effects amplified or supressed by crosstalk. Exploration of these mechanisms may unveil novel therapeutic targets or biomarkers that would improve current treatment strategies for VaD.
Admissions to a Low-Resource Neonatal Unit in Malawi Using a Mobile App and Dashboard: A 1-Year Digital Perinatal Outcome Audit
Authors: Mgusha Yamikani , Nkhoma Deliwe Bernadette , Chiume Msandeni , Gundo Beatrice , Gundo Rodwell , Shair Farah , Hull-Bailey Tim , Lakhanpaul Monica , Lorencatto Fabianna , Heys Michelle , Crehan Caroline
Published: December 2021

Introduction: Understanding the extent and cause of high neonatal deaths rates in Sub-Saharan Africa is a challenge, especially in the presence of poor-quality and inaccurate data. The NeoTree digital data capture and quality improvement system has been live at Kamuzu Central Hospital, Neonatal Unit, Malawi, since April 2019.

Objective: To describe patterns of admissions and outcomes in babies admitted to a Malawian neonatal unit over a 1-year period via a prototype data dashboard.

Methods: Data were collected prospectively at the point of care, using the NeoTree app, which includes digital admission and outcome forms containing embedded clinical decision and management support and education in newborn care according to evidence-based guidelines. Data were exported and visualised using Microsoft Power BI. Descriptive and inferential analysis statistics were executed using R.

Results: Data collected via NeoTree were 100% for all mandatory fields and, on average, 96% complete across all fields. Coverage of admissions, discharges, and deaths was 97, 99, and 91%, respectively, when compared with the ward logbook. A total of 2,732 neonates were admitted and 2,413 (88.3%) had an electronic outcome recorded: 1,899 (78.7%) were discharged alive, 12 (0.5%) were referred to another hospital, 10 (0.4%) absconded, and 492 (20%) babies died. The overall case fatality rate (CFR) was 204/1,000 admissions. Babies who were premature, low birth weight, out born, or hypothermic on admission, and had significantly higher CFR. Lead causes of death were prematurity with respiratory distress (n = 252, 51%), neonatal sepsis (n = 116, 23%), and neonatal encephalopathy (n = 80, 16%). The most common perceived modifiable factors in death were inadequate monitoring of vital signs and suboptimal management of sepsis. Two hundred and two (8.1%) neonates were HIV exposed, of whom a third [59 (29.2%)] did not receive prophylactic nevirapine, hence vulnerable to vertical infection.

Conclusion: A digital data capture and quality improvement system was successfully deployed in a low resource neonatal unit with high (1 in 5) mortality rates providing and visualising reliable, timely, and complete data describing patterns, risk factors, and modifiable causes of newborn mortality. Key targets for quality improvement were identified. Future research will explore the impact of the NeoTree on quality of care and newborn survival.
Numerical Investigation on Dynamic Response and Failure Modes of Rock Slopes with Weak Interlayers Using Continuum-Discontinuum Element Method
Authors: Wang Chengwen , Liu Xiaoli , Song Danqing , Wang Enzhi , Zhang Jianmin
Published: December 2021

In order to better understand the dynamic response and failure modes of rock slopes containing weak interlayers subjected to earthquake excitation, a series of numerical simulations were carried out using the continuum-discontinuum element method (CDEM), considering the influence of seismic amplitude and weak interlayers inclination. The seismic response characteristics of slopes were systematically analyzed according to the waveform characteristics, amplification effect, equivalent crack ratio, etc. The numerical results show that the acceleration waveform characteristics and peak ground displacement (PGD) amplification coefficient have good correspondence with the dynamic failure process of landslides. Comprehensive analysis of waveform characteristics and PGD amplification coefficient can determine the damage time, damage location, and damage degree of landslides. The landslide process can be divided into three stages according to the equivalent crack ratio: rapid generation of a large number of microcracks, expansion and aggregation of microcracks, and penetration of micro-cracks and the formation of slip surfaces. The equivalent crack ratio provides a new idea for evaluating slope stability. In addition, under the combination of different amplitudes and weak interlayers, these earthquake-induced landslides exhibit different failure modes: the failure of the gentle-dip slope is mainly local rockfall; The mid-dip and steep-dip slopes with small amplitudes experience “tensile cracking-slip-collapsing” failure; The steep-dip slopes under strong earthquake failed in the form of “tensile cracking-slip-slope extrusion-collapsing”. The research results are of great significance for a deeper understanding of the formation mechanism of rock landslides with weak interlayers and the prevention of such landslide disasters.
Bioaccumulation and Tolerance Indices of Cadmium in Wheat Plants Grown in Cadmium-Spiked Soil: Health Risk Assessment
Authors: Halim Md Abdul , Rahman Mohammad Mahmudur , Mondal Debapriya , Megharaj Mallavarapu , Naidu Ravi
Published: December 2021

Farmers use wastewater for irrigation in many developing countries, for example Bangladesh, India, China, Sri Lanka and Vietnam because they have limited access to clean water. This study explored cadmium (Cd) bioaccumulation in two spring wheat cultivars (cv. Mustang and Lancer), which were grown in different concentrations of Cd (0,1, 2, 4, and 8 mg kg−1) in agricultural soils. The half maximum inhibitory concentration (IC50) values were 4.21 ± 0.29 and 4.02 ± 0.95, respectively, whereas the maximum health risk index (HRI) was 3.85 ± 0.049 and 5.33 ± 0.271, respectively, for Mustang and Lancer. In other words, the malondialdehyde content increased significantly in Mustang (around five-fold) and Lancer (around four-fold) compared with the control treatment. Results revealed that Cd content was well above the acceptable limit (HRI >1) in the two cultivars when exposed to different levels of Cd stress. The tolerant cultivar (Mustang) has potential to chelate Cd in the nonedible parts of plants in variable fractions and can be used efficiently to improve growth and macro- and micro-nutrients content while reducing Cd concentration in plants in Cd-contaminated soil. It can also diminish the HRI, which may help to protect humans from Cd risks. The two cultivars’ nutrient availability and sorption capacity significantly shape their survival and adaptability under Cd stress. Based on what is documented in the current study, we can conclude that Mustang is more tolerant and poses fewer health hazards to people than Lancer because of its capacity to maintain grain macro- and micro-nutrients under Cd stress.
High-Dimensional Mediation Analysis Based on Additive Hazards Model for Survival Data
Authors: Cui Yidan , Luo Chengwen , Luo Linghao , Yu Zhangsheng
Published: December 2021

Mediation analysis has been extensively used to identify potential pathways between exposure and outcome. However, the analytical methods of high-dimensional mediation analysis for survival data are still yet to be promoted, especially for non-Cox model approaches. We propose a procedure including “two-step” variable selection and indirect effect estimation for the additive hazards model with high-dimensional mediators. We first apply sure independence screening and smoothly clipped absolute deviation regularization to select mediators. Then we use the Sobel test and the BH method for indirect effect hypothesis testing. Simulation results demonstrate its good performance with a higher true-positive rate and accuracy, as well as a lower false-positive rate. We apply the proposed procedure to analyze DNA methylation markers mediating smoking and survival time of lung cancer patients in a TCGA (The Cancer Genome Atlas) cohort study. The real data application identifies four mediate CpGs, three of which are newly found.
Construction and Clinical Translation of Causal Pan-Cancer Gene Score Across Cancer Types
Authors: Tao Shiyue , Ye Xiangyu , Pan Lulu , Fu Minghan , Huang Peng , Peng Zhihang , Yang Sheng
Published: December 2021

Pan-cancer strategy, an integrative analysis of different cancer types, can be used to explain oncogenesis and identify biomarkers using a larger statistical power and robustness. Fine-mapping defines the casual loci, whereas genome-wide association studies (GWASs) typically identify thousands of cancer-related loci and not necessarily have a fine-mapping component. In this study, we develop a novel strategy to identify the causal loci using a pan-cancer and fine-mapping assumption, constructing the CAusal Pan-cancER gene (CAPER) score and validating its performance using internal and external validation on 1,287 individuals and 985 cell lines. Summary statistics of 15 cancer types were used to define 54 causal loci in 15 potential genes. Using the Cancer Genome Atlas (TCGA) training set, we constructed the CAPER score and divided cancer patients into two groups. Using the three validation sets, we found that 19 cancer-related variables were statistically significant between the two CAPER score groups and that 81 drugs had significantly different drug sensitivity between the two CAPER score groups. We hope that our strategies for selecting causal genes and for constructing CAPER score would provide valuable clues for guiding the management of different types of cancers.
Extracellular CIRP Induces Macrophage Extracellular Trap Formation Via Gasdermin D Activation
Authors: Lee Yongchan , Reilly Bridgette , Tan Chuyi , Wang Ping , Aziz Monowar
Published: December 2021

Extracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern promoting inflammation and tissue injury. During bacterial or viral infection, macrophages release DNA decorated with nuclear and cytoplasmic proteins known as macrophage extracellular traps (METs). Gasdermin D (GSDMD) is a pore-forming protein that has been involved in extracellular trap formation in neutrophils. We hypothesized that eCIRP induces MET formation by activating GSDMD. Human monocytic cell line THP-1 cells were differentiated with phorbol 12-myristate 13-acetate (PMA) and treated with recombinant murine (rm) CIRP. The MET formation was detected by three methods: time-lapse fluorescence microscopy (video imaging), colorimetry, and ELISA. Cleaved forms of GSDMD, and caspase-1 were detected by Western blotting. Treatment of THP-1 cells with rmCIRP increased MET formation as revealed by SYTOX Orange Staining assay in a time- and dose-dependent manner. METs formed by rmCIRP stimulation were further confirmed by extracellular DNA, citrullinated histone H3, and myeloperoxidase. Treatment of THP-1 cells with rmCIRP significantly increased the cleaved forms of caspase-1 and GSDMD compared to PBS-treated cells. Treatment of macrophages with caspase-1, and GSDMD inhibitors z-VAD-fmk, and disulfiram, separately, significantly decreased rmCIRP-induced MET formation. We also confirmed rmCIRP-induced MET formation using primary cells murine peritoneal macrophages. These data clearly show that eCIRP serves as a novel inducer of MET formation through the activation of GSDMD and caspase-1.
Milk From Women Diagnosed With COVID-19 Does Not Contain SARS-CoV-2 RNA but Has Persistent Levels of SARS-CoV-2-Specific IgA Antibodies
Authors: Pace Ryan M. , Williams Janet E. , Järvinen Kirsi M. , Meehan Courtney L. , Martin Melanie A. , Ley Sylvia H. , Barbosa-Leiker Celestina , Andres Aline , Yeruva Laxmi , Belfort Mandy B. , Caffé Beatrice , Navarrete Alexandra D. , Lackey Kimberly A. , Pace Christina D. W. , Gogel Alexandra C. , Fehrenkamp Bethaney D. , Klein Miranda , Young Bridget E. , Rosen-Carole Casey , Diaz Nichole , Gaw Stephanie L. , Flaherman Valerie , McGuire Mark A. , McGuire Michelle K. , Seppo Antti E.
Published: December 2021

Background

Limited data are available regarding the balance of risks and benefits from human milk and/or breastfeeding during and following maternal infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Objective

To investigate whether SARS-CoV-2 can be detected in milk and on the breast after maternal coronavirus disease 2019 (COVID-19) diagnosis; and characterize concentrations of milk immunoglobulin (Ig) A specific to the SARS-CoV-2 spike glycoprotein receptor binding domain (RBD) during the 2 months after onset of symptoms or positive diagnostic test.

Methods

Using a longitudinal study design, we collected milk and breast skin swabs one to seven times from 64 lactating women with COVID-19 over a 2-month period, beginning as early as the week of diagnosis. Milk and breast swabs were analyzed for SARS-CoV-2 RNA, and milk was tested for anti-RBD IgA.

Results

SARS-CoV-2 was not detected in any milk sample or on 71% of breast swabs. Twenty-seven out of 29 (93%) breast swabs collected after breast washing tested negative for SARS-CoV-2. Detection of SARS-CoV-2 on the breast was associated with maternal coughing and other household COVID-19. Most (75%; 95% CI, 70-79%; n=316) milk samples contained anti-RBD IgA, and concentrations increased (P=.02) during the first two weeks following onset of COVID-19 symptoms or positive test. Milk-borne anti-RBD IgA persisted for at least two months in 77% of women.

Conclusion

Milk produced by women with COVID-19 does not contain SARS-CoV-2 and is likely a lasting source of passive immunity via anti-RBD IgA. These results support recommendations encouraging lactating women to continue breastfeeding during and after COVID-19 illness.
The Immunological Impact of IL-1 Family Cytokines on the Epidermal Barrier
Authors: Macleod Tom , Berekmeri Anna , Bridgewood Charlie , Stacey Martin , McGonagle Dennis , Wittmann Miriam
Published: December 2021

The skin barrier would not function without IL-1 family members, but their physiological role in the immunological aspects of skin barrier function are often overlooked. This review summarises the role of IL-1 family cytokines (IL-1α, IL-1β, IL-1Ra, IL-18, IL-33, IL-36α, IL-36β, IL-36γ, IL-36Ra, IL-37 and IL-38) in the skin. We focus on novel aspects of their interaction with commensals and pathogens, the important impact of proteases on cytokine activity, on healing responses and inflammation limiting mechanisms. We discuss IL-1 family cytokines in the context of IL-4/IL-13 and IL-23/IL-17 axis-driven diseases and highlight consequences of human loss/gain of function mutations in activating or inhibitory pathway molecules. This review highlights recent findings that emphasize the importance of IL-1 family cytokines in both physiological and pathological cutaneous inflammation and emergent translational therapeutics that are helping further elucidate these cytokines.
Pathways to Justice, Equity, Diversity, and Inclusion in Marine Science and Conservation
Authors: Johri Shaili , Carnevale Maria , Porter Lindsay , Zivian Anna , Kourantidou Melina , Meyer Erin L. , Seevers Jessica , Skubel Rachel A.
Published: December 2021

Marine conservation sciences have traditionally been, and remain, non-diverse work environments with many barriers to justice, equity, diversity, and inclusion (JEDI). These barriers disproportionately affect entry of early career scientists and practitioners and limit the success of marine conservation professionals from under-represented, marginalized, and overburdened groups. These groups specifically include women, LGBTQ+, Black, Indigenous, and people of color (BIPOC). However, the issues also arise from the global North/South and East/West divide with under-representation of scientists from the South and East in the global marine conservation and science arena. Persisting inequities in conservation, along with a lack of inclusiveness and diversity, also limit opportunities for innovation, cross-cultural knowledge exchange, and effective implementation of conservation and management policies. As part of its mandate to increase diversity and promote inclusion of underrepresented groups, the Diversity and Inclusion committee of the Society for Conservation Biology-Marine Section (SCB Marine) organized a JEDI focus group at the Sixth International Marine Conservation Congress (IMCC6) which was held virtually. The focus group included a portion of the global cohort of IMCC6 attendees who identified issues affecting JEDI in marine conservation and explored pathways to address those issues. Therefore, the barriers and pathways identified here focus on issues pertinent to participants’ global regions and experiences. Several barriers to just, equitable, diverse, and inclusive conservation science and practice were identified. Examples included limited participation of under-represented minorities (URM) in research networks, editorial biases against URM, limited professional development and engagement opportunities for URM and non-English speakers, barriers to inclusion of women, LGBTQ+, and sensory impaired individuals, and financial barriers to inclusion of URM in all aspects of marine conservation and research. In the current policy brief, we explore these barriers, assess how they limit progress in marine conservation research and practice, and seek to identify initiatives for improvements. We expect the initiatives discussed here to advances practices rooted in principles of JEDI, within SCB Marine and, the broader conservation community. The recommendations and perspectives herein broadly apply to conservation science and practice, and are critical to effective and sustainable conservation and management outcomes.
Living in a Fluctuating Environment Increases Tolerance to Marine Heatwaves in the Free-Living Coralline Alga Phymatolithon lusitanicum
Authors: Schubert Nadine , Santos Rui , Silva João
Published: December 2021

Recently, increased attention is being paid to the importance of environmental history in species’ responses to climate-change related stressors, as more variable and heterogeneous environments are expected to select for higher levels of plasticity in species tolerance traits, compared to stable conditions. For example, organisms inhabiting environments with highly fluctuating thermal regimes might be less susceptible to the increasing frequency and intensity of marine heatwaves (MHWs). In this study, we assessed the metabolic and calcification responses of the rhodolith-bed forming Phymatolithon lusitanicum, from a coastal region that is strongly influenced by frequent changes between upwelling and downwelling conditions, to a simulated MHW scenario, with and without prior exposure to a moderate thermal stress. This allowed determining not only the influence of the species’ long-term thermal history on its resilience against MHWs, but also the rhodoliths capacity for short-term thermal stress memory and its importance during posterior MHW-exposure. Our findings indicate that the rhodoliths experienced negative impacts on daily net primary production (DNP) and calcification (DNC) during the MHW. The effect on the former was only temporary at the beginning of the MHW, while DNC was highly impacted, but exhibited a quick recovery after the event, suggesting a high resilience of the species. Furthermore, prior exposure to a moderate temperature increase, such as those occurring frequently in the natural habitat of the species, mitigated the effects of a subsequent MHW on DNP, while promoting a faster recovery of DNC after the event. Thus, our findings (1) support the hypothesis that benthic organisms living in nearshore habitats may benefit from the natural short-term temperature fluctuations in these environments with an increased resistance to MHW impacts and (2) provide first-time evidence for thermally induced stress memory in coralline algae.
The Combined Effects of Ocean Acidification and Heavy Metals on Marine Organisms: A Meta-Analysis
Authors: Jin Peng , Zhang Jiale , Wan Jiaofeng , Overmans Sebastian , Gao Guang , Ye Mengcheng , Dai Xiaoying , Zhao Jingyuan , Xiao Mengting , Xia Jianrong
Published: December 2021

Ocean acidification (OA) may interact with anthropogenic pollutants, such as heavy metals (HM), to represent a threat to marine organisms and ecosystems. Here, we perform a quantitative meta-analysis to examine the combined effects of OA and heavy metals on marine organisms. The results reveal predominantly additive interactions (67%), with a considerable proportion of synergistic interactions (25%) and a few antagonistic interactions (8%). The overall adverse effects of heavy metals on marine organisms were alleviated by OA, leading to a neutral impact of heavy metals in combination with OA. However, different taxonomic groups showed large variabilities in their responses, with microalgae being the most sensitive when exposed to heavy metals and OA, and having the highest proportion of antagonistic interactions. Furthermore, the variations in interaction type frequencies are related to climate regions and heavy metal properties, with antagonistic interactions accounting for the highest proportion in temperate regions (28%) and when exposed to Zn (52%). Our study provides a comprehensive insight into the interactive effects of OA and HM on marine organisms, and highlights the importance of further investigating the responses of different marine taxonomic groups from various geographic locations to the combined stress of OA and HM.
Dynamic Species Distribution Models in the Marine Realm: Predicting Year-Round Habitat Suitability of Baleen Whales in the Southern Ocean
Authors: El-Gabbas Ahmed , Van Opzeeland Ilse , Burkhardt Elke , Boebel Olaf
Published: December 2021

Species distribution models (SDMs) relate species information to environmental conditions to predict potential species distributions. The majority of SDMs are static, relating species presence information to long-term average environmental conditions. The resulting temporal mismatch between species information and environmental conditions can increase model inference’s uncertainty. For SDMs to capture the dynamic species-environment relationships and predict near-real-time habitat suitability, species information needs to be spatiotemporally matched with environmental conditions contemporaneous to the species’ presence (dynamic SDMs). Implementing dynamic SDMs in the marine realm is highly challenging, particularly due to species and environmental data paucity and spatiotemporally biases. Here, we implemented presence-only dynamic SDMs for four migratory baleen whale species in the Southern Ocean (SO): Antarctic minke, Antarctic blue, fin, and humpback whales. Sightings were spatiotemporally matched with their respective daily environmental predictors. Background information was sampled daily to describe the dynamic environmental conditions in the highly dynamic SO. We corrected for spatial sampling bias by sampling background information respective to the seasonal research efforts. Independent model evaluation was performed on spatial and temporal cross-validation. We predicted the circumantarctic year-round habitat suitability of each species. Daily predictions were also summarized into bi-weekly and monthly habitat suitability. We identified important predictors and species suitability responses to environmental changes. Our results support the propitious use of dynamic SDMs to fill species information gaps and improve conservation planning strategies. Near-real-time predictions can be used for dynamic ocean management, e.g., to examine the overlap between habitat suitability and human activities. Nevertheless, the inevitable spatiotemporal biases in sighting data from the SO call for the need for improving sampling effort in the SO and using alternative data sources (e.g., passive acoustic monitoring) in future SDMs. We further discuss challenges of calibrating dynamic SDMs on baleen whale species in the SO, with a particular focus on spatiotemporal sampling bias issues and how background information should be sampled in presence-only dynamic SDMs. We also highlight the need to integrate visual and acoustic data in future SDMs on baleen whales for better coverage of environmental conditions suitable for the species and avoid constraints of using either data type alone.
Transport and Fate of 137Cs Released From Multiple Sources in the North Atlantic and Arctic Oceans
Authors: Maderich Vladimir , Kim Kyeong Ok , Bezhenar Roman , Jung Kyung Tae , Martazinova Vazira , Brovchenko Igor
Published: December 2021

The North Atlantic and Arctic oceans, along with the North Pacific, are the main reservoirs of anthropogenic radionuclides introduced in the past 75 years. The POSEIDON-R compartment model was applied to the North Atlantic and Arctic oceans to reconstruct 137Cs contamination in 1945–2020 due to multiple sources: global fallout, exchange flows with other oceans, point-source inputs in the ocean from reprocessing plants and other nuclear facilities, the impact of the Chernobyl accident and secondary contamination resulting from river runoff and redissolution from bottom sediments. The model simulated the marine environment as a system of 3D compartments comprising the water column, bottom sediment, and biota. The dynamic model described the transfer of 137Cs through the pelagic and benthic food chains. The simulation results were validated using the marine database MARIS. The calculated concentrations of 137Cs in the seaweed and non-piscivorous and piscivorous pelagic fish mostly followed the concentration of 137Cs in water. The concentration in coastal predator fish lagged behind the concentration in water as a result of a diet that includes both pelagic and benthic organisms. The impact of each considered source on the total concentration of 137Cs in non-piscivorous fish in the regions of interest was analyzed. Whereas the contribution from global fallout dominated in 1960–1970, in 1970–1990, the contribution of 137Cs released from reprocessing plants exceeded the contributions from other sources in almost all considered regions. Secondary contamination due to river runoff was less than 4% of ocean influx. The maximum total inventory of 137Cs in the Arctic Ocean (31,122 TBq) was reached in 1988, whereas the corresponding inventory in the bottom sediment was approximately 6% of the total. The general agreement between simulated and observed 137Cs concentrations in water and bottom sediment was confirmed by the estimates of geometric mean and geometric standard deviation, which varied from 0.89 to 1.29 and from 1.22 to 1.87, respectively. The approach used is useful to synthesize measurement and simulation data in areas with observational gaps. For this purpose, 13 representative regions in the North Atlantic and Arctic oceans were selected for monitoring by using the “etalon” method for classification.
Large-Scale Statistical Learning for Mass Transport Prediction in Porous Materials Using 90,000 Artificially Generated Microstructures
Authors: Prifling Benedikt , Röding Magnus , Townsend Philip , Neumann Matthias , Schmidt Volker
Published: December 2021

Effective properties of functional materials crucially depend on their 3D microstructure. In this paper, we investigate quantitative relationships between descriptors of two-phase microstructures, consisting of solid and pores and their mass transport properties. To that end, we generate a vast database comprising 90,000 microstructures drawn from nine different stochastic models, and compute their effective diffusivity and permeability as well as various microstructural descriptors. To the best of our knowledge, this is the largest and most diverse dataset created for studying the influence of 3D microstructure on mass transport. In particular, we establish microstructure-property relationships using analytical prediction formulas, artificial (fully-connected) neural networks, and convolutional neural networks. Again, to the best of our knowledge, this is the first time that these three statistical learning approaches are quantitatively compared on the same dataset. The diversity of the dataset increases the generality of the determined relationships, and its size is vital for robust training of convolutional neural networks. We make the 3D microstructures, their structural descriptors and effective properties, as well as the code used to study the relationships between them available open access.
Assessment of Local Observation of Atomic Ordering in Alloys via the Radial Distribution Function: A Computational and Experimental Approach
Authors: Greenhalgh Alexander D. , Sanjeewa Liurukara D. , Luszczek Piotr , Maroulas Vasileios , Rios Orlando , Keffer David J.
Published: December 2021

As a powerful analytical technique, atom probe tomography (APT) has the capacity to acquire the spatial distribution of millions of atoms from a complex sample. However, extracting information at the Ångstrom-scale on atomic ordering remains a challenge due to the limits of the APT experiment and data analysis algorithms. The development of new computational tools enable visualization of the data and aid understanding of the physical phenomena such as disorder of complex crystalline structures. Here, we report progress towards this goal using two steps. We describe a computational approach to evaluate atomic ordering in the crystal structure by generating radial distribution functions (RDF). Atomic ordering is rendered as the Fractional Cumulative Radial Distribution Function (FCRDF) which allows for greater visibility of local compositions at short range in the structure. Further, we accommodate in the analysis additional parameters such as uncertainty in the atomic coordinates and the atomic abundance to ascertain short-range ordering in APT data sets. We applied the FCRDF analysis to synthetic and experimental APT data sets for Ni3Al. The ability to observe a signal of atomic ordering consistent with the known L12 crystal structure is heavily dependent on spatial uncertainty, irrespective of abundance. Detection of atomic ordering is subject to an upper limit of spatial uncertainty of atoms described with Gaussian distributions with a standard deviation of 1.3 Å. The FCRDF analysis was also applied to the APT data set for a six-component alloy, Al1.3CoCrCuFeNi. In this case, we are currently able to visualize elemental segregation at the nanoscale, though unambiguous identification of atomic ordering at the Ångstrom (nearest-neighbor) scale remains a goal.
Effectiveness of Combined Strategies for the Prevention of Hypothermia Measured by Noninvasive Zero-Heat Flux Thermometer During Cesarean Section
Authors: Cotoia Antonella , Mariotti Paola Sara , Ferialdi Claudia , Del Vecchio Pasquale , Beck Renata , Zaami Simona , Cinnella Gilda
Published: December 2021

Background: Perioperative hypothermia (body temperature <36°C) is a common complication of anesthesia increasing the risk for maternal cardiovascular events and coagulative disorders, and can also influence neonatal health. The aim of our work was to evaluate the impact of combined warming strategies on maternal core temperature, measured with the SpotOn. We hypothesized that combined modalities of active warming prevent hypothermia in pregnant women undergoing cesarean delivery with spinal anesthesia.

Methods: Seventy-eight pregnant women were randomly allocated into three study groups receiving warmed IV fluids and forced-air warming (AW), warmed IV fluids (WF), or no warming (NW). Noninvasive core temperature device (SpotOn) measured maternal core temperature intraoperatively and for 30 min after surgery. Maternal mean arterial pressure, incidence of shivering, thermal comfort and newborn's APGAR, axillary temperature, weight, and blood gas analysis were also recorded.

Results: Incidence of hypothermia was of 0% in AW, 4% in WF, and 47% in NW. Core temperature in AW was constantly higher than WF and NW groups. Incidence of shivering in perioperative time was significantly lower in AW and WF groups compared with the NW group (p < 0.04). Thermal comfort was higher in both AW and WF groups compared with NW group (p = 0.02 and p = 0.008, respectively). There were no significant differences among groups for the other evaluated parameters.

Conclusion: Combined modalities of active warming are effective in preventing perioperative hypothermia. The routine uses of combined AW are suggested in the setting of cesarean delivery.
Clinical Characteristics and Prognostic Risk Factors of Patients With Proven Invasive Pulmonary Aspergillosis: A Single-Institution Retrospective Study
Authors: Tong Xiang , Liu Tao , Jiang Kexin , Wang Dongguang , Liu Sitong , Wang Ye , Fan Hong
Published: December 2021

Background: The mortality and burden of medical costs associated with invasive pulmonary aspergillosis (IPA) is very high. Currently, the clinical features and prognostic factors of patients with proven IPA are not very clear, especially in the Chinese population. In this retrospective analysis, we aimed to identify the clinical features and prognostic factors of patients with proven IPA.

Methods: The diagnostic criteria for proven IPA were based on the international consensus of the EORTC/MSG. Data of patients with proven IPA at the West China Hospital of Sichuan University between January 2012 and December 2018 were collected. The optimal cut-off value of continuous variables was determined by Receiver Operating Characteristic curve and maximum Youden's index. Finally, using the Cox regression analysis to identify correlations between the clinical parameters associated with morbidity.

Results: A total of 117 patients with proven IPA were included in the study, and 32 (27.4%) patients died during the follow-up period. Compared with the survivor group, elderly, patients with comorbidities, and patients undergoing chemotherapy and the level of inflammatory biomarkers [erythrocyte sedimentation rate, platelet count, interleukin-6, C-reactive protein (CRP)] in the non-survivor group were higher, while the albumin level was lower (P = 0.018). The imaging features were consolidation, nodules, cavities, pleural effusion, ground-glass shadows, and halo signs in order. Overall, 41.0% patients had mixed imaging features. The results suggested the most appropriate cut-off value of age and CRP were 60 years and 14.1 mg/L, respectively. The multivariate Cox regression analysis suggested that advanced age (>60 years) [hazard ratio (HR): 10.7, confidence interval (CI): 2.5–44.9, P < 0.001), undergoing chemotherapy (HR: 9.5, CI: 2.7–32.9, P < 0.001), presence of pleural effusion (HR: 5.74, CI: 1.6–20.8, P = 0.008), and increased CRP levels (>14.1 mg/L) (HR: 6.3, CI: 1.2–34.3, P = 0.033) were risk factors for all-cause mortality in patients with proven aspergillosis.

Conclusions: This study showed that the prognosis of proven IPA is poor, and the age >60 years, undergoing chemotherapy, pleural effusion on CT image, and CRP levels >14.1 mg/L may be as risk factors for mortality in patients with proven IPA. large samples and real-world studies are needed to confirm these results in the future.
Survival Outcomes and Prognostic Predictors in Patients With Malignant Struma Ovarii
Authors: Li Sijian , Kong Shujun , Wang Xiaoxue , Zhang Xinyue , Yin Min , Yang Jiaxin
Published: December 2021

Background: Malignant struma ovarii (MSO) is an extremely rare ovarian malignant tumor and there is limited data on the survival outcomes and prognostic predictors of MSO. The objectives of this study were to investigate the disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS) rates of patients with MSO, and also evaluate the prognostic factors in this population.

Methods: A retrospective study was conducted and 194 cases of MSO were selected. DFS was assessed by the logistic regression, OS by the Kaplan–Meier method, and DSS was evaluated by the Cox regression.

Results: The median age of these patients was 46.0 years; 142 cases (73.2%) were confined to the ovary and 52 cases (26.8%) had extraovarian metastasis at the initial diagnosis of MSO. During the follow-up, 75.3% of these patients showed no evidence of disease and 18.0% were alive with disease. Only 13 deaths occurred, with 10 attributed to MSO. The 5, 10, and 15-year OS rates were 91.4, 87.7, and 83.5%, respectively. The 5, 10, and 15-year DSS rates were 93.8, 90.0, and 85.7%, respectively. Logistic regression revealed that International Federation of Gynecology and Obstetrics (FIGO) stage IV was the only risk factor for DFS [p < 0.001; odds ratio (OR) 7.328; 95% CI 3.103–16.885, FIGO stage IV vs. stage I; p = 0.021; OR 4.750, 95% CI 1.264–17.856, FIGO stage IV vs. stage II-III]. The multivariate Cox regression analysis showed that poor differentiation was the only risk factor for both OS (p = 0.005, OR 6.406; 95% CI 1.730–23.717) and DSS (p = 0.001, OR 9.664; 95% CI 2.409–38.760), while age ≥45 years was the prognostic predictor for OS (p = 0.038, OR 4.959; 95% CI 1.093–22.508).

Conclusion: Survival outcomes were excellent in patients with MSO, irrespective of the treatment strategy, FIGO stage IV, age ≥45 years, and poor differentiation of tumors were the independent risk factors.
Peroxisome Proliferator-Activated Receptor α Activation Protects Retinal Ganglion Cells in Ischemia-Reperfusion Retinas
Authors: Yao Fei , Zhang Xuan , Yao Xueyan , Ren Xiaohua , Xia Xiaobo , Jiang Jian , Ding Lexi
Published: December 2021

Background and Objective: Retinal ischemia-reperfusion (IR) leads to massive loss of retinal ganglion cells (RGC) and characterizes several blind-causing ophthalmic diseases. However, the mechanism related to retinal IR is controversial, and a drug that could prevent the RGC loss caused by IR is still lacking. This study aimed to investigate the role of endogenous retinal peroxisome proliferator-activated receptor (PPAR)α and the therapeutic effect of its agonist, fenofibric acid (FA), in IR-related retinopathy.

Materials and Methods: Fenofibric acid treatment was applied to the Sprague–Dawley rats with IR and retinal cell line 28 cells with oxygen-glucose deprivation (OGD) (an in vitro model of IR). Western blotting, real-time PCR, and immunofluorescence were used to examine the expression levels of PPARα, glial fibrillary acidic protein (GFAP), and cyclooxygenase-2 (COX2). Hematoxylin and eosin (HE) staining, propidium iodide (PI) staining, retrograde tracing, and flash visual-evoked potential (FVEP) were applied to assess RGC injury and visual function.

Results: Retinal IR down-regulated PPARα expression in vitro and in vivo. Peroxisome proliferator-activated receptor α activation by FA promoted survival of RGCs, mitigated thinning of the ganglion cell complex, and decreased the latency of positive waves of FVEPs after IR injury. Further, FA treatment enhanced the expression of endogenous PPARα and suppressed the expression of GFAP and COX2 significantly.

Conclusion: Peroxisome proliferator-activated receptor α activation by FA is protective against RGC loss in retinal IR condition, which may occur by restoring PPARα expression, inhibiting activation of glial cells, and suppressing retinal inflammation. All these findings indicate the translational potential of FA in treating IR-related retinopathy.