bluuebunny/crossref_metadata_2025 huggingface dataset:
Sea Ice‐Driven Variability in the Pacific Subantarctic Mode Water Formation Regions
Authors: Sanders R. N. C. , Meijers A. J. S. , Holland P. R. , Naveira Garabato A. C.
Published: December 2023

Subantarctic Mode Water (SAMW) forms north of the Subantarctic Front, in regions of deep winter mixed layers, and is important to the absorption and storage of anthropogenic CO2 and heat. Two SAMW pools exist in the Pacific, a lighter Central mode (CPSAMW), and a denser Southeast mode (SEPSAMW). Both have experienced significant interannual variability in thickness and properties in recent years. We compute mixed layer temperature and salinity budgets for the two SAMW formation regions, to determine the relative contribution of processes driving variability in the properties of mixed layers that subduct to form SAMW. The dominant drivers of temperature and salinity variability are shown to be surface fluxes, horizontal advection, and entrainment of deeper water. Salt advection into each SAMW formation region is found to be strongly correlated with changes in sea ice area in the northern Ross Sea, with lags of up to 2 years. Further correlation is found between meridional salt advection in the southeast Pacific formation regions, and sea ice area in the northern Amundsen/Bellingshausen seas, suggesting that freshwater derived from sea ice melt reaches the SEPSAMW formation region within 6 months. In 2016, strong advective freshening of the SEPSAMW formation region, linked to increased winter sea ice in the Amundsen/Bellingshausen seas, led to anomalously fresh mixed layers. However, a regime change in Antarctic sea ice in 2016 resulted in a subsequent lack of the usual advective freshening in the SEPSAMW formation region, driving increased salinity of the mixed layer the following year.
Simulation of Temperature Extremes Over West Africa With MPAS
Authors: Tanimoune Laouali Ibrahim , Smiatek Gerhard , Kunstmann Harald , Abiodun Babatunde J.
Published: December 2023

A large ensemble of 51 simulations with the Model for Prediction Across Scales (MPAS) has been applied to assess its ability to reproduce extreme temperatures and heat waves in the area of West Africa. With its global approach the model avoids transition errors influencing the performance of limited area climate models. The MPAS simulations were driven with sea surface temperature (SST) and sea ice extent as the only boundary condition. The results reveal moderate cold biases in the range from −0.6° to −0.9°C for the daily mean temperature and −1.2° to −2.0°C for the area mean of the daily maximum temperature. The bias in the number of tropical nights ranges from +3 to −10 days. An underestimation by up to 50% is also present regarding the number of summer days. The heat wave duration index is underestimated regionally by 10%–60%. MPAS simulations are generally closer to the reanalysis results than they are to the observational reference. The results from long term runs and from short term runs with selected SST years are similar. Shortcomings in the reproduction of the temperature and precipitation indices found in the present investigation indicate that the global MPAS approach does provide a fidelity similar to that of the regional climate models.
Prominent Role of Sulfate Reduction in Considerable Sulfur Retention in a Subtropical Soil
Authors: Yu Qian , Mulder Jan , Si Gaoyue , Yu Longfei , Kang Ronghua , Liu Kaiyi , Hao Jiming , Duan Lei
Published: December 2023

The sulfur biogeochemical cycle controls the sulfur dynamics in the soil. In contrast to almost all deposited sulfur leaching out in temperate catchments, approximately 80% of the deposited S is retained in the catchments in subtropical regions. However, the mechanisms for sulfur retention were unclear, hindering the understanding of potential threats of legacy sulfur with environmental changes. Here, we demonstrated that sulfate reduction (as sulfide fixed in soil) was a prominent yet overlooked mechanism for sulfur retention in addition to the widely recognized sulfate adsorption in soil, based on a study on soil sulfur storage and stable isotope signatures within entire soil profiles in a typical subtropical catchment in China. Using a dual‐isotopic model, the sulfate reduction flux was further determined to be 30% of the S deposition. Due to a lot of deposited sulfur fixed via sulfate reduction, the release of soil legacy sulfur would be less in response to decreasing sulfur deposition compared to the projections only considering adsorption. However, the remobilization of large amounts of reduced S should be regarded as a threat to the environment under climate change in the future.
Antigen-induced chimeric antigen receptor multimerization amplifies on-tumor cytotoxicity
Authors: Sun Yan , Yang Xiu-Na , Yang Shuang-Shuang , Lyu Yi-Zhu , Zhang Bing , Liu Kai-Wen , Li Na , Cui Jia-Chen , Huang Guang-Xiang , Liu Cheng-Lin , Xu Jie , Mi Jian-Qing , Chen Zhu , Fan Xiao-Hu , Chen Sai-Juan , Chen Shuo
Published: December 2023

Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity, safeguarding receptor activation, and facilitating amplification of signal transduction across the cellular membrane. However, cell-surface antigen-induced multimerization (dubbed AIM herein) has not yet been consciously leveraged in chimeric antigen receptor (CAR) engineering for enriching T cell-based therapies. We co-developed ciltacabtagene autoleucel (cilta-cel), whose CAR incorporates two B-cell maturation antigen (BCMA)-targeted nanobodies in tandem, for treating multiple myeloma. Here we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated cytotoxicity. Crystallographic analysis of BCMA–nanobody complexes revealed atomic details of antigen–antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in solution. BCMA-induced nanobody CAR multimerization enhanced cytotoxicity, alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release, towards myeloma-derived cells. Our results provide a framework for contemplating the AIM approach in designing next-generation CARs.
Gut microbiota composition in depressive disorder: a systematic review, meta-analysis, and meta-regression
Authors: Gao Mingxue , Wang Jizhi , Liu Penghong , Tu Hongwei , Zhang Ruiyu , Zhang Yanyan , Sun Ning , Zhang Kerang
Published: December 2023

Studies investigating gut microbiota composition in depressive disorder have yielded mixed results. The aim of our study was to compare gut microbiome between people with depressive disorder and healthy controls. We did a meta-analysis and meta-regression of studies by searching PubMed, Web of Science, Embase, Scopus, Ovid, Cochrane Library, ProQuest, and PsycINFO for articles published from database inception to March 07, 2022. Search strategies were then re-run on 12 March 2023 for an update. We undertook meta-analyses whenever values of alpha diversity and Firmicutes, Bacteroidetes (relative abundance) were available in two or more studies. A random-effects model with restricted maximum-likelihood estimator was used to synthesize the effect size (assessed by standardized mean difference [SMD]) across studies. We identified 44 studies representing 2091 patients and 2792 controls. Our study found that there were no significant differences in patients with depressive disorder on alpha diversity indices, Firmicutes and Bacteroidetes compared with healthy controls. In subgroup analyses with regional variations(east/west) as a predictor, patients who were in the West had a lower Chao1 level (SMD −0.42[−0.74 to −0.10]). Subgroup meta-analysis showed Firmicutes level was decreased in patients with depressive disorder who were medication-free (SMD −1.54[−2.36 to −0.72]), but Bacteroidetes level was increased (SMD −0.90[0.07 to 1.72]). In the meta-regression analysis, six variables cannot explain the 100% heterogeneity of the studies assessing by Chao1, Shannon index, Firmicutes, and Bacteroidetes. Depleted levels of Butyricicoccus, Coprococcus, Faecalibacterium, Fusicatenibacter, Romboutsia, and enriched levels of Eggerthella, Enterococcus, Flavonifractor, Holdemania, Streptococcus were consistently shared in depressive disorder. This systematic review and meta-analysis found that psychotropic medication and dietary habit may influence microbiota. There is reliable evidence for differences in the phylogenetic relationship in depressive disorder compared with controls, however, method of measurement and method of patient classification (symptom vs diagnosis based) may affect findings. Depressive disorder is characterized by an increase of pro-inflammatory bacteria, while anti-inflammatory butyrate-producing genera are depleted.
Mechanical and chemical surface treatment enhances bond strength between zirconia and orthodontic brackets: an in vitro study
Authors: Limpuangthip Nareudee , Surintanasarn Atikom , Vitavaspan Ploylada
Published: December 2023

Objectives

To assess the shear bond strength (SBS) between metal orthodontic brackets and zirconia after receiving different mechanical and chemical surface treatments, and different types of resin adhesive. The failure mode of each treatment protocol was also evaluated.

Materials and methods

The present in vitro experimental study consisted of six surface treatment protocols with two different resin adhesives. One-hundred and forty-four rectangular-shaped 3 mol% yttrium-stabilized tetragonal zirconia polycrystal blocks were milled, sintered, and embedded in acrylic resin. They were randomly divided into three mechanical (none, air abrasion, and bur grinding) and two chemical surface treatment conditions (no primer and Z-primer). The specimens were divided into two groups according to the resin adhesive received: self-cured (RelyX U200) and light-cured adhesives (Transbond XT). The SBS between the metal bracket and zirconia was tested using a universal testing machine (1-mm/min crosshead speed), and the failure mode was evaluated. Differences in SBS and failure mode were analyzed using Welch ANOVA followed by post-hoc comparison and Fisher’s Exact test, respectively.

Results

Bur grinding produced the highest SBS, followed by air abrasion. Z-primer application typically provided a higher SBS regardless of resin adhesive used (p < 0.001). Without primer application, RelyX U200 provided a higher SBS than Transbond XT (p < 0.001). After grinding, using Z-primer and RelyX U200 resulted in a higher SBS than no primer and using Transbond XT (p < 0.001). Adhesive failure at the zirconia–adhesive interface occurred only when Transbond XT was applied without bur grinding, and when using Transbond XT after grinding, but no Z-primer application.

Conclusion

Bur grinding combined with applying an MDP-containing primer and resin adhesive enhances the SBS between zirconia and metal orthodontic brackets.
A delay in vesicle endocytosis by a C-terminal fragment of N-cadherin enhances Aβ synaptotoxicity
Authors: Teng Zenghui , Kartalou Georgia-Ioanna , Dagar Sushma , Fraering Patrick C. , Lessmann Volkmar , Gottmann Kurt
Published: December 2023

Synaptotoxic Aβ oligomers are thought to play a major role in the early pathology of Alzheimer´s disease (AD). However, the molecular mechanisms involved in Aβ-induced synaptic dysfunction and synapse damage remain largely unclear. Previously, Aβ synaptotoxicity has been reported to be enhanced by increased levels of a C-terminal fragment of the synaptic adhesion molecule N-cadherin that is generated by proteolytic shedding of the extracellular domains [1]. To address the molecular mechanisms involved in this process, we have now studied the functional synaptic changes induced by C-terminal fragments (CTF1) of synaptic adhesion proteins. We used synaptophysin-pHluorin (SypHy) fluorescence imaging to monitor synaptic vesicle exo- and endocytosis in cultures of mouse cortical neurons. We increased the levels of C-terminal fragments of synaptic adhesion proteins by pharmacologically inhibiting γ-secretase, which further degrades CTF1 fragments. We found that this intervention caused a delay in synaptic vesicle endocytosis. A similar effect was induced by overexpression of N-cadherin CTF1, but not by overexpression of Neurexin3β CTF1. Based on these observations, we further studied whether directly modulating synaptic vesicle endocytosis enhances Aβ synaptotoxicity. We pharmacologically induced a delayed synaptic vesicle endocytosis by a low concentration of the endocytosis inhibitor dynasore. This treatment enhanced synaptoxicity of Aβ oligomers as indicated by a reduced frequency of miniature postsynaptic currents. In conclusion, we propose that delayed endocytosis results in prolonged exposure of synaptic vesicle membranes to the extracellular space, thus enabling enhanced vesicle membrane binding of Aβ oligomers. This might in turn promote the endocytic uptake of toxic Aβ oligomers and might thus play an important role in intracellular Aβ-mediated synaptotoxicity in AD.
Glowing gels and pipettes aplenty: how do commercial stock image banks portray genetic tests?
Authors: Horton Rachel , Boyle Leah , Weller Susie , Lucassen Anneke
Published: December 2023

News stories and patient-facing material about genetic tests are often illustrated by images, but the content of such images and the messages they propagate are rarely scrutinised. Stock image banks were searched to identify a hundred images relating to genetic tests and analysed using a multimodal critical discourse approach, aiming to identify what the images featured, how they were composed, and what they communicated about genetic testing. We found that images tended to focus on technical aspects of sample processing (for example, pipetting) and drew on older technologies (for example slab gel electrophoresis) when representing data arising from genetic tests. Composition choices like focussing images around pipette tips, or emphasising colour or brightness of electrophoretic bands, represented genetic testing as precise, unambiguous and illuminating. Only 7% of images featured a person having a genetic test, and only one image alluded to communication of genetic results. Current popular visual representations of genetic testing rarely highlight the possibility of uncertain or non-diagnostic outcomes, and may contribute to high public expectations of informativeness and certainty from such tests.
Light-induced LLPS of the CRY2/SPA1/FIO1 complex regulating mRNA methylation and chlorophyll homeostasis in Arabidopsis
Authors: Jiang Bochen , Zhong Zhenhui , Gu Lianfeng , Zhang Xueyang , Wei Jiangbo , Ye Chang , Lin Guifang , Qu Gaoping , Xiang Xian , Wen Chenjin , Hummel Maureen , Bailey-Serres Julia , Wang Qin , He Chuan , Wang Xu , Lin Chentao
Published: December 2023

Light regulates chlorophyll homeostasis and photosynthesis via various molecular mechanisms in plants. The light regulation of transcription and protein stability of nuclear-encoded chloroplast proteins have been extensively studied, but how light regulation of mRNA metabolism affects abundance of nuclear-encoded chloroplast proteins and chlorophyll homeostasis remains poorly understood. Here we show that the blue light receptor cryptochrome 2 (CRY2) and the METTL16-type m6A writer FIONA1 (FIO1) regulate chlorophyll homeostasis in response to blue light. In contrast to the CRY2-mediated photo-condensation of the mRNA adenosine methylase (MTA), photoexcited CRY2 co-condenses FIO1 only in the presence of the CRY2-signalling protein SUPPRESSOR of PHYTOCHROME A (SPA1). CRY2 and SPA1 synergistically or additively activate the RNA methyltransferase activity of FIO1 in vitro, whereas CRY2 and FIO1, but not MTA, are required for the light-induced methylation and translation of the mRNAs encoding multiple chlorophyll homeostasis regulators in vivo. Our study demonstrates that the light-induced liquid–liquid phase separation of the photoreceptor/writer complexes is commonly involved in the regulation of photoresponsive changes of mRNA methylation, whereas the different photo-condensation mechanisms of the CRY/FIO1 and CRY/MTA complexes explain, at least partially, the writer-specific functions in plant photomorphogenesis.
Atomistic fracture in bcc iron revealed by active learning of Gaussian approximation potential
Authors: Zhang Lei , Csányi Gábor , van der Giessen Erik , Maresca Francesco
Published: December 2023

The prediction of atomistic fracture mechanisms in body-centred cubic (bcc) iron is essential for understanding its semi-brittle nature. Existing atomistic simulations of the crack-tip under mode-I loading based on empirical interatomic potentials yield contradicting predictions and artificial mechanisms. To enable fracture prediction with quantum accuracy, we develop a Gaussian approximation potential (GAP) using an active learning strategy by extending a density functional theory (DFT) database of ferromagnetic bcc iron. We apply the active learning algorithm and obtain a Fe GAP model with a converged model uncertainty over a broad range of stress intensity factors (SIFs) and for four crack systems. The learning efficiency of the approach is analysed, and the predicted critical SIFs are compared with Griffith and Rice theories. The simulations reveal that cleavage along the original crack plane is the atomistic fracture mechanism for {100} and {110} crack planes at T = 0 K, thus settling a long-standing issue. Our work also highlights the need for a multiscale approach to predicting fracture and intrinsic ductility, whereby finite temperature, finite loading rate effects and pre-existing defects (e.g., nanovoids, dislocations) should be taken explicitly into account.
Arithmetic skills are associated with left fronto-temporal gray matter volume in 536 children and adolescents
Authors: Viesel-Nordmeyer Nurit , Prado Jérôme
Published: December 2023

There are large individual differences in arithmetic skills. Although a number of brain-wide association studies have attempted to identify the neural correlates of these individual differences, studies have focused on relatively small sample sizes and have yielded inconsistent results. In the current voxel-based morphometry study, we merged six structural imaging datasets of children and adolescents (from 7.5 to 15 years) whose levels of arithmetic skills were assessed, leading to a combined sample ofn = 536. Controlling for individual differences in age, gender, as well as language, and intelligence, we found a unique positive relation between arithmetic skill and gray matter volume in the left inferior frontal gyrus (IFG) and middle temporal gyrus (MTG). Our results suggest that individual differences in arithmetic skills are associated with structural differences in left fronto-temporal areas, rather than in regions of the parietal cortex and hippocampus that are often associated with arithmetic processing.
Canadian Covid-19 pandemic public health mitigation measures at the province level
Authors: Akanteva Anna , Dick David W. , Amiraslani Shirin , Heffernan Jane M.
Published: December 2023

The Covid-19 pandemic has prompted governments across the world to enforce a range of public health interventions. We introduce the Covid-19 Policy Response Canadian tracker (CPRCT) database that tracks and records implemented public health measures in every province and territory in Canada. The implementations are recorded on a four-level ordinal scale (0–3) for three domains, (Schools, Work, and Other), capturing differences in degree of response. The data-set allows the exploration of the effects of public health mitigation on the spread of Covid-19, as well as provides a near-real-time record in an accessible format that is useful for a diverse range of modeling and research questions.
A database of hourly wind speed and modeled generation for US wind plants based on three meteorological models
Authors: Millstein Dev , Jeong Seongeun , Ancell Amos , Wiser Ryan
Published: December 2023

In 2022, wind generation accounted for ~10% of total electricity generation in the United States. As wind energy accounts for a greater portion of total energy, understanding geographic and temporal variation in wind generation is key to many planning, operational, and research questions. However, in-situ observations of wind speed are expensive to make and rarely shared publicly. Meteorological models are commonly used to estimate wind speeds, but vary in quality and are often challenging to access and interpret. The Plant-Level US multi-model WIND and generation (PLUSWIND) data repository helps to address these challenges. PLUSWIND provides wind speeds and estimated generation on an hourly basis at almost all wind plants across the contiguous United States from 2018–2021. The repository contains wind speeds and generation based on three different meteorological models: ERA5, MERRA2, and HRRR. Data are publicly accessible in simple csv files. Modeled generation is compared to regional and plant records, which highlights model biases and errors and how they differ by model, across regions, and across time frames.
A news-based climate policy uncertainty index for China
Authors: Ma Yan-Ran , Liu Zhenhua , Ma Dandan , Zhai Pengxiang , Guo Kun , Zhang Dayong , Ji Qiang
Published: December 2023

Climate policies can have a significant impact on the economy. However, these policies have often been associated with uncertainty. Quantitative assessment of the socioeconomic impact of climate policy uncertainty is equally or perhaps more important than looking at the policies themselves. Using a deep learning algorithm—the MacBERT model—this study constructed indices of Chinese climate policy uncertainty (CCPU) at the national, provincial and city levels for the first time. The CCPU indices are based on the text mining of news published by a set of major newspapers in China. A clear upward trend was found in the indices, demonstrating increasing policy uncertainties in China in addressing climate change. There is also evidence of clear regional heterogeneity in subnational indices. The CCPU dataset can provide a useful source of information for government actors, academics and investors in understanding the dynamics of climate policies in China. These indices can also be used to investigate the empirical relationship between climate policy uncertainty and other socioeconomic factors in China.
Combined effects of smoking and HIV infection on the occurrence of aging-related manifestations
Authors: Boyer Laurent , Zebachi Sonia , Gallien Sébastien , Margarit Laurent , Ribeiro Baptista Bruno , Lopez-Zaragoza José-Luis , D’Humières Thomas , Zerah Françoise , Hue Sophie , Derumeaux Geneviève , Adnot Serge , Audureau Etienne , Lelièvre Jean-Daniel
Published: December 2023

Both HIV-1 infection and smoking may contribute to the development of ageing-related manifestations affecting the prognosis of people living with HIV, but it is unclear whether HIV and smoking exert their effects independently or interact by potentiating each other. We conducted a cross-sectional study in 192 people living with HIV aged- and gender-matched with 192 HIV-uninfected controls, assessing the relative effect of HIV-1/smoking status on lung function (FEV1), bone mineral density (BMD), appendicular skeletal muscle mass index (ASMI), aortic pulse-wave velocity (PWV), insulin resistance (HOMA-IR) and renal function. In both unadjusted and adjusted analyses, FEV1, BMD and ASMI significantly differed according to smoking/HIV status, with the worst parameters found in HIV-1 infected patients currently smoking, and BMD and ASMI decreased to a lesser extent in HIV-1 infected patients formerly smoking (> 10 pack-years). Values in people living with HIV with < 10 pack-years exposure were of similar magnitude to those from controls. Regarding PWV, HOMA-R and eGFR, no significant differences were found, with the exception of eGFR values which were globally lower in HIV-1 infected patients. In conclusion HIV infection and smoking acted synergistically and were associated with a wasting phenotype combining muscle mass and bone mineral reduction.

Clinical Trial Registration (registrar, website, and registration number), where applicable: CPP 10-023, 09-027, 10-034.
High-throughput ligand profile characterization in novel cell lines expressing seven heterologous insect olfactory receptors for the detection of volatile plant biomarkers
Authors: Zboray Katalin , Toth Adam V. , Miskolczi Tímea D. , Pesti Krisztina , Casanova Emilio , Kreidl Emanuel , Mike Arpad , Szenes Áron , Sági László , Lukacs Peter
Published: December 2023

Agriculturally important crop plants emit a multitude of volatile organic compounds (VOCs), which are excellent indicators of their health status and their interactions with pathogens and pests. In this study, we have developed a novel cellular olfactory panel for detecting fungal pathogen-related VOCs we had identified in the field, as well as during controlled inoculations of several crop plants. The olfactory panel consists of seven stable HEK293 cell lines each expressing a functional Drosophila olfactory receptor as a biosensing element along with GCaMP6, a fluorescent calcium indicator protein. An automated 384-well microplate reader was used to characterize the olfactory receptor cell lines for their sensitivity to reference VOCs. Subsequently, we profiled a set of 66 VOCs on all cell lines, covering a concentration range from 1 to 100 μM. Results showed that 49 VOCs (74.2%) elicited a response in at least one olfactory receptor cell line. Some VOCs activated the cell lines even at nanomolar (ppb) concentrations. The interaction profiles obtained here will support the development of biosensors for agricultural applications. Additionally, the olfactory receptor proteins can be purified from these cell lines with sufficient yields for further processing, such as structure determination or integration with sensor devices.
Association between electroencephalogram-based sleep characteristics and physical health in the general adult population
Authors: Iwagami Masao , Seol Jaehoon , Hiei Tetsuro , Tani Akihiro , Chiba Shigeru , Kanbayashi Takashi , Kondo Hideaki , Tanaka Takashi , Yanagisawa Masashi
Published: December 2023

We examined the associations between electroencephalogram (EEG)-based sleep characteristics and physical health parameters in general adults via a cross-sectional study recruiting 100 volunteers aged 30–59 years. Sleep characteristics were measured at home using a portable multichannel electroencephalography recorder. Using the k-means +  +  clustering method, according to 10 EEG-based parameters, participants were grouped into better (n = 39), middle (n = 46), and worse (n = 15) sleep groups. Comparing 50 physical health parameters among the groups, we identified four signals of difference (P < 0.05), including systolic (sBP) and diastolic blood pressure (dBP), γ-glutamyl transpeptidase (γ-GTP), and serum creatinine, where sBP reached a Bonferroni-corrected threshold (P < 0.001). The sBP was higher by 7.9 (95% confidence interval 1.9–13.9) and 15.7 (7.3–24.0) mmHg before adjustment and 5.4 (− 0.1–10.9) and 8.7 (1.1–16.3) mmHg after adjustment for age, sex, body mass index, smoking, drinking habits, and 3% oxygen desaturation index in the middle and worse sleep groups, respectively, than in the better group. As another approach, among 500 combinations of EEG-based and physical health parameters, there were 45 signals of correlation, of which 4 (N1% and sBP, dBP, γ-GTP, and triglycerides) reached a Bonferroni-corrected threshold (P < 0.0001). Thus, EEG-based sleep characteristics are associated with several physical health parameters, particularly sBP.
Circulating miRNA profiles in COVID-19 patients and meta-analysis: implications for disease progression and prognosis
Authors: Gao Liangliang , Kyubwa Espoir M. , Starbird Mark A. , Diaz de Leon Jesus , Nguyen Michelle , Rogers Claude J. , Menon Naresh
Published: December 2023

We compared circulating miRNA profiles of hospitalized COVID-positive patients (n = 104), 27 with acute respiratory distress syndrome (ARDS) and age- and sex-matched healthy controls (n = 18) to identify miRNA signatures associated with COVID and COVID-induced ARDS. Meta-analysis incorporating data from published studies and our data was performed to identify a set of differentially expressed miRNAs in (1) COVID-positive patients versus healthy controls as well as (2) severe (ARDS+) COVID vs moderate COVID. Gene ontology enrichment analysis of the genes these miRNAs interact with identified terms associated with immune response, such as interferon and interleukin signaling, as well as viral genome activities associated with COVID disease and severity. Additionally, we observed downregulation of a cluster of miRNAs located on chromosome 14 (14q32) among all COVID patients. To predict COVID disease and severity, we developed machine learning models that achieved AUC scores between 0.81–0.93 for predicting disease, and between 0.71–0.81 for predicting severity, even across diverse studies with different sample types (plasma versus serum), collection methods, and library preparations. Our findings provide network and top miRNA feature insights into COVID disease progression and contribute to the development of tools for disease prognosis and management.
Call combination patterns in Icelandic killer whales (Orcinus orca)
Authors: Selbmann Anna , Miller Patrick J. O. , Wensveen Paul J. , Svavarsson Jörundur , Samarra Filipa I. P.
Published: December 2023

Acoustic sequences have been described in a range of species and in varying complexity. Cetaceans are known to produce complex song displays but these are generally limited to mysticetes; little is known about call combinations in odontocetes. Here we investigate call combinations produced by killer whales (Orcinus orca), a highly social and vocal species. Using acoustic recordings from 22 multisensor tags, we use a first order Markov model to show that transitions between call types or subtypes were significantly different from random, with repetitions and specific call combinations occurring more often than expected by chance. The mixed call combinations were composed of two or three calls and were part of three call combination clusters. Call combinations were recorded over several years, from different individuals, and several social clusters. The most common call combination cluster consisted of six call (sub-)types. Although different combinations were generated, there were clear rules regarding which were the first and last call types produced, and combinations were highly stereotyped. Two of the three call combination clusters were produced outside of feeding contexts, but their function remains unclear and further research is required to determine possible functions and whether these combinations could be behaviour- or group-specific.
Model-informed health and socio-economic benefits of enhancing global equity and access to Covid-19 vaccines
Authors: Italia Matteo , Della Rossa Fabio , Dercole Fabio
Published: December 2023

We take a model-informed approach to the view that a global equitable access (GEA) to Covid-19 vaccines is the key to bring this pandemic to an end. We show that the equitable redistribution (proportional to population size) of the currently available vaccines is not sufficient to stop the pandemic, whereas a 60% increase in vaccine access (the global share of vaccinated people) would have allowed the current distribution to stop the pandemic in about a year of vaccination, saving millions of people in poor countries. We then investigate the interplay between access to vaccines and their distribution among rich and poor countries, showing that the access increase to stop the pandemic gets minimized at + 32% by the equitable distribution (− 36% in rich countries and + 60% in poor ones). To estimate the socio-economic benefits of a vaccination campaign with enhanced global equity and access (eGEA), we compare calibrated simulations of the current scenario with a hypothetical, vaccination-intensive scenario that assumes high rollouts (shown however by many rich and poor countries during the 2021–2022 vaccination campaign) and an improved equity from the current 2.5:1 to a 2:1 rich/poor-ratio of the population fractions vaccinated per day. Assuming that the corresponding + 130% of vaccine production is made possible by an Intellectual Property waiver, we show that the money saved on vaccines globally by the selected eGEA scenario overcomes the 5-year profit of the rights holders in the current situation. This justifies compensation mechanisms in exchange for the necessary licensing agreements. The good news is that the benefits of this eGEA scenario are still relevant, were we ready to implement it now.
Physical characterization of late-type contact binary systems observed by LAMOST: a comprehensive statistical analysis
Authors: Abdel Rahman H. I. , Darwish Mohamed
Published: December 2023

This paper presents a catalog of approximately 1800 Eclipsing W UMa systems (EWs) using parameters from LAMOST, VSX, ZTF and Gaia. Our detailed statistical analysis includes frequency distributions of parameters, confidence intervals, and hypothesis testing to provide deeper insights into the physical properties of this important eclipsing binary class. We focus on key parameters, including Period, Effective Temperature, Surface Gravity, metallicity, Radial Velocity, and spectral type of the systems. Our study reveals that the mean values for period, effective temperature, logarithmic surface gravity, metallicity, and radial velocity for EW systems are 0.377 days, 5775 K, 4, -0.185, and -4.085 km/s, respectively. The 95% confidence intervals for these parameters are 0.372 to 0.382 days, 5730 to 5820 K, -0.202 to -0.168, 3.97 to 4.03, and -6.47 to -1.7 km/s, respectively. Hypothesis testing of the estimated intervals results in the acceptance of the null hypothesis, indicating that EW systems are characterized within the specified limits. Our study also confirms that the majority of EW systems are late-type stars, primarily classified as F spectral type, followed by G and K. Interestingly, among the sample, 88 systems are classified as A spectral type, with a mean surface temperature of 7400 K. We examine the correlation between orbital periods and atmospheric parameters in the VSX and ZTF catalogs. While ZTF periods align well with established relations (correlation coefficient: 0.74), a weaker correlation is found in the VSX catalog. This highlights the need for a revision of VSX periods for improved accuracy in the studied sample of EWs.
Fracture-matrix fluid exchange in oil-bearing unconventional mudstones
Authors: Moore Johnathan , Crandall Dustin , Sanguinito Sean , Valenza John J.
Published: December 2023

The poromechanical properties of unconventional reservoir materials are in large part dictated by their mineralogy. Since these properties govern the response to stress experienced during hydraulic fracturing, fluid production, and fluid injection, they play a central role in the formation of microcracks or bedding delaminations which ultimately dominate mass transport. In this work we study access to the porosity of end member unconventional reservoir materials, where the end members are predominantly dictated by carbonate content. Access to the porosity is quantified using state of the art 3D x-ray computed tomography coupled with physics informed data analytics. Xenon gas, which attenuates x-rays, provides a spatiotemporal map of access to the porosity. The accessible porosity is quantified over a range of net confining stress relevant to the manmade disturbances listed above. These experiments demonstrate that heavily carbonated mudstones are nearly impermeable at the core (~ cm) scale, while carbonate free analogues afford better access to the microstructure. Consistent with previous qualitative 2D radiographs, access to the interior of the clastic mudstones is first observed along planar microcracks, followed by slow penetration into the surrounding matrix. Physics informed data analytics of the 3D tomography measurements presented here show that these microcracks do not permit uniform access to the adjacent rock matrix. In addition, variation of the effective pressure elucidates the mechanisms that govern fracture/matrix fluid exchange. Under conditions consistent with hydrocarbon production fluid accumulates in the immediate vicinity of the nearest microcrack. While there is clear evidence that, as intended, part of this accumulation is from the more distant matrix, fluid is also squeezed out of the microcrack. The fluid build-up at the microcrack indicates that migration out of the rock is hindered by the coupled poroelastic response of the microcrack and adjacent rock matrix. We show that these mechanisms ultimately account for the meager oil recovery factors realized in practice. These insights have implications for making reservoir scale predictions based on core scale observations, and provide a basis for devising new asset development techniques to access more porosity, and enhance fluid extraction. Finally, these findings shed light on key features and mechanisms that govern shale storage capacity, with relevance to other important industrial processes, such as geologic CO2 storage.
Reproducible and clinically translatable deep neural networks for cervical screening
Authors: Ahmed Syed Rakin , Befano Brian , Lemay Andreanne , Egemen Didem , Rodriguez Ana Cecilia , Angara Sandeep , Desai Kanan , Jeronimo Jose , Antani Sameer , Campos Nicole , Inturrisi Federica , Perkins Rebecca , Kreimer Aimee , Wentzensen Nicolas , Herrero Rolando , del Pino Marta , Quint Wim , de Sanjose Silvia , Schiffman Mark , Kalpathy-Cramer Jayashree
Published: December 2023

Cervical cancer is a leading cause of cancer mortality, with approximately 90% of the 250,000 deaths per year occurring in low- and middle-income countries (LMIC). Secondary prevention with cervical screening involves detecting and treating precursor lesions; however, scaling screening efforts in LMIC has been hampered by infrastructure and cost constraints. Recent work has supported the development of an artificial intelligence (AI) pipeline on digital images of the cervix to achieve an accurate and reliable diagnosis of treatable precancerous lesions. In particular, WHO guidelines emphasize visual triage of women testing positive for human papillomavirus (HPV) as the primary screen, and AI could assist in this triage task. In this work, we implemented a comprehensive deep-learning model selection and optimization study on a large, collated, multi-geography, multi-institution, and multi-device dataset of 9462 women (17,013 images). We evaluated relative portability, repeatability, and classification performance. The top performing model, when combined with HPV type, achieved an area under the Receiver Operating Characteristics (ROC) curve (AUC) of 0.89 within our study population of interest, and a limited total extreme misclassification rate of 3.4%, on held-aside test sets. Our model also produced reliable and consistent predictions, achieving a strong quadratic weighted kappa (QWK) of 0.86 and a minimal %2-class disagreement (% 2-Cl. D.) of 0.69%, between image pairs across women. Our work is among the first efforts at designing a robust, repeatable, accurate and clinically translatable deep-learning model for cervical screening.
High resolution simulation of basilar artery infarct and flow within the circle of Willis
Authors: McCullough Jon W. S. , Coveney Peter V.
Published: December 2023

On a global scale, cerebro- and cardiovascular diseases have long been one of the leading causes of death and disability and their prevalence appears to be increasing in recent times. Understanding potential biomarkers and risk factors will help to identify individuals potentially at risk of suffering an ischemic stroke. However, the widely variable construction of the cerebral vasculature makes it difficult to provide a specific assessment without the knowledge of a patient’s physiology. In this paper we use the 3D blood flow simulator HemeLB to study flow within three common structural variations of the circle of Willis during and in the moments after a blockage of the basilar artery. This tool, based on the lattice Boltzmann method, allows the 3D flow entering the basilar artery to be finely controlled to replicate the cessation of blood feeding this particular vessel—we demonstrate this with several examples including a sudden halt to flow and a gradual loss of flow over three heartbeat cycles. In this work we start with an individualised 3D representation of a full circle of Willis and then construct two further domains by removing the left or right posterior communicating arteries from this geometry. Our results indicate how, and how quickly, the circle of Willis is able to redistribute flow following such a stroke. Due to the choice of infarct, the greatest reduction in flow was observed in the posterior cerebral arteries where flow was reduced by up to 70% in some cases. The high resolution domains used in this study permit the velocity magnitude and wall shear stress to be analysed at key points during and following the stroke. The model we present here indicates how personalised vessels are required to provide the best insight into stroke risk for a given individual.
A novel biomarker of MMP-cleaved cartilage intermediate layer protein-1 is elevated in patients with rheumatoid arthritis, ankylosing spondylitis and osteoarthritis
Authors: Port Helena , Hausgaard Cecilie Møller , He Yi , Maksymowych Walter P. , Wichuk Stephanie , Sinkeviciute Dovile , Bay-Jensen Anne-Christine , Holm Nielsen Signe
Published: December 2023

Rheumatic joints have an altered cartilage turnover. Cartilage intermediate layer protein 1 (CILP-1) is secreted from articular chondrocytes and deposited into the cartilage extracellular matrix. We developed an immunoassay targeting a Matrix Metalloproteinase (MMP)-generated neo-epitope of CILP-1, named CILP-M. Human articular cartilage was cleaved with proteolytic enzymes and CILP-M levels were measured. We also quantified CILP-M in two studies from patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and osteoarthritis (OA) and explored the monitoring and prognostic potential of CILP-M in TNF-α inhibitory treatment and modified Stoke AS Spine Score (mSASSS) progression. CILP-M was generated by MMP-1, -8 and -12. In the discovery study, CILP-M was significantly higher in patients with RA, AS and OA than healthy donors (p < 0.01, p < 0.001, p < 0.05) with an area under the curve (AUC) between the diseased groups and healthy donors > 0.95 (p < 0.001). In the validation study, patients with RA and AS had significantly higher CILP-M levels than healthy controls (p < 0.001) and AUC > 0.90 (p < 0.001). Patients with AS treated with TNF- α inhibitory treatment in the validation study had significantly lower CILP-M levels after treatment (p = 0.004). CILP-M may provide useful insights into cartilage degradation processes in rheumatic diseases.
Research on reasonable layout parameters of working faces based on the concept of harmonic extraction to reduce the damage of coal seam waiting for upward mining
Authors: Jing Chai , Zhicheng Han , Weiming Lv , Haitao Zhu , Shuhong Hou
Published: December 2023

Based on the idea of harmonic extraction, the problem of reducing the damage of the coal seam waiting for upward mining. Using the theoretical analysis method, a schematic diagram of coordinated mining along the dip direction of coal seam is established, and the calculation method of reasonable layout parameters of coal seam working face early mining is given. Based on the upward mining problem of the No.1 coal seam in the fifth panel of Zaoquan Coal Mine, the influence parameters of the No.2 coal seam, No.6 coal seam and No.7 coal seam mining on the No.1 coal seam were determined by similar simulation test. Then, the layout parameters of working face were determined. The research method of numerical calculation was used to evaluate the degree and uniformity of movement and deformation of the No.1 coal seam, combining five indicators: subsidence, horizontal movement, inclined deformation, curvature deformation, and horizontal deformation. The results indicate that when the working face is arranged using the layout parameters provided in this article, it can promote the further subsidence of the No.1 coal seam at the position of the remaining coal pillar. The movement and deformation indicators of the No.1 coal seam all reach the most uniform degree of the geological mining conditions, which can effectively offset the uneven deformation problem of the No.1 coal seam caused by the influence of the remaining coal pillars, making multiple mining operations a favorable condition for upward mining and achieving the goal of reducing the damage of the No.1 coal seam.
GC-MS profiling of Pistachio vera L., and effect of antioxidant and antimicrobial compounds of it's essential oil compared to chemical counterparts
Authors: Shahdadi Fatemeh , Khorasani Sepideh , Salehi-Sardoei Ali , Fallahnajmabadi Farshad , Fazeli-Nasab Bahman , Sayyed R. Z.
Published: December 2023

All elements of the pistachio tree are considered raw pistachio by-products. The soft hull makes up the majority of these by-products. It contains proteins, fats, minerals, vitamins, phenolics contents (TPC), and antioxidants. Early smiling pistachios are one of the most important sources of pistachio contamination with aflatoxin in the garden and processing stages. The present study aimed to evaluate pistachio hull essential oil (EO) composition, and antioxidant and antimicrobial properties under in vitro conditions. TPC, antioxidant, and antimicrobial activity were measured using the Folin–Ciocalteu reagent, 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method, and serial dilution titration method, respectively. A gas chromatography system with a mass spectrometer (GC-MS) was utilized to determine the chemical components of the EO. The findings revealed that the quantity of TPC and anti-radical activity in IC50 were 245.43 mg gallic acid/mL and 206.32 µL/L, respectively. The free radical absorption activity of DPPH (%) increased with EO content. The inhibitory activity of EO on Staphylococcus aureus and Bacillus subtilis was much lower than that of streptomycin and penicillin. Aspergillus flavus was effectively inhibited by pistachio hull EO, comparable to fluconazole. The results obtained from GC-MS showed that the major compounds in pistachio hull essential oil include α-pinene (47.36%), terpinolene (10.57%), limonene (9.13%), and L-bornyl acetate (8.57%). The findings indicated that pistachio hull EO has potent antibacterial and antioxidant components and can be employed as a natural antimicrobial and antioxidant in food systems.