bluuebunny/crossref_metadata_2025 huggingface dataset:
“The Air Is Blue with Robert Elsmere”: The Public Reading of Theological Novels
Authors: DeWitt Anne
Published: May 2022

The popularity of Mary Ward's novelRobert Elsmere(1888) has been attributed to readers who identified with the title character's loss of faith. This article offers a new account ofRobert Elsmere's sales as it considers the book alongsideJohn Inglesant(1881), another best-selling novel of religious experience. I argue that readers were drawn not to the representation of the protagonists’ experience but to the chance the books offered of exploring an expanding range of religious positions. Their appeal thus lay not in their resonances with private religious experience but in the way they fostered what I call “public reading.”
How to Foster Informal Learning
Authors: Welk Svenja , Kortsch Timo , Kauffeld Simone
Published: May 2022

Abstract: This article explains how three different informal learning strategies are influenceable by feedback and if and how feedback further mediates the impact of the cultural value of power distance on informal learning. We also examined the three informal learning strategies regarding their stableness and separability. A survey at two different timepoints was administered to technical staff members from a globally acting company from the automotive industry within six different countries ( N = 777). We tested our hypotheses by conducting a multigroup factor analysis based on a bootstrap-based structural equation model. Results showed informal learning strategies to be stable over time and cultures. Additionally, feedback availability showed to be a predictor of informal learning. The effect of power distance on informal learning is also mediated by feedback availability. The overall results show that informal learning strategies can be influenced differently in various countries.
Pathways, Form Drag, and Turbulence in Simulations of an Ocean Flowing Through an Ice Mélange
Authors: Hughes Kenneth G.
Published: May 2022

A collection of calved icebergs frozen in place by surrounding sea ice (a “mélange”) is common in many Greenlandic fjords. Being an obstacle to ocean currents, a mélange alters ocean dynamics and thermodynamics over the many kilometers that it extends out in front of the glacier. Here we focus on a set of dynamics—flow pathways, form drag, and turbulence—using many simulations that each resolve the flow around hundreds of volume‐occupying, but otherwise passive, cuboid “icebergs.” Some streaks of fast flow do arise where currents are squeezed through gaps between icebergs but, on average, the near‐surface current is slowed. Maximum average currents speeds are instead found at or below the drafts of the deepest icebergs. Form drag scales with U2h when few icebergs exist and smoothly transitions to scaling with NUh2 when many icebergs exist, where U is the far‐field flow velocity, N is the buoyancy frequency, and h is a typical iceberg draft. Turbulence predominately occurs in wakes behind the icebergs (as opposed to below icebergs due to internal wave breaking). Consequently, turbulent dissipation is elevated at depths less than or near the drafts of larger icebergs (∼100 m).
A Self Training Mechanism With Scanty and Incompletely Annotated Samples for Learning‐Based Cloud Detection in Whole Sky Images
Authors: Ye Liang , Wang Yufeng , Cao Zhiguo , Yang Zhibiao , Min Huasong
Published: May 2022

Cloud detection is one of important tasks in automatic ground‐based cloud observation systems with ground‐based cloud images. Most supervised methods need substantial annotated samples for model training, while the pixel‐level annotation costs a lot. In this letter, a self‐training mechanism is proposed to significantly reduce the requirement of annotated samples. With a number of original images, only a few images need to be annotated (even incompletely), and a local region classifier model can be initialized with the annotated samples. Then the model is retrained iteratively using unlabeled samples with high confidence pseudo labels given by a fusion decision. The finely trained model can classify the local regions into “cloud” or “sky”. The experiments show that the proposed mechanism is effective for several classifiers. The proposed method can outperform unsupervised methods and achieve comparable results with fully supervised learning methods but using much fewer annotated samples.
Active Hurricane Season Expected in the Atlantic Ocean
Authors: Duncombe Jenessa
Published: May 2022

La Ni�a conditions and warm ocean temperatures have set the stage for another busy tropical storm year.
Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: the 2022 update of the recommendations by ERIC, the European Research Initiative on CLL
Authors: Agathangelidis Andreas , Chatzidimitriou Anastasia , Chatzikonstantinou Thomas , Tresoldi Cristina , Davis Zadie , Giudicelli Véronique , Kossida Sofia , Belessi Chrysoula , Rosenquist Richard , Ghia Paolo , Langerak Anton W. , Davi Frédéric , Stamatopoulos Kostas ,   on behalf of ERIC, the European Research Initiative on CLL
Published: May 2022

The somatic hypermutation (SHM) status of the clonotypic immunoglobulin heavy variable (IGHV) gene is a critical biomarker for assessing the prognosis of patients with chronic lymphocytic leukemia (CLL). Importantly, independent studies have documented that IGHV SHM status is also a predictor of responses to therapy, including both chemoimmunotherapy (CIT) and novel, targeted agents. Moreover, immunogenetic analysis in CLL has revealed that different patients may express (quasi)identical, stereotyped B cell receptor immunoglobulin (BcR IG) and are classified into subsets based on this common feature. Patients in certain stereotyped subsets display consistent biology, clinical presentation, and outcome that are distinct from other patients, even with concordant IGHV gene SHM status. All of the above highlights the relevance of immunogenetic analysis in CLL, which is considered a cornerstone for accurate risk stratification and clinical decision making. Recommendations for robust immunogenetic analysis exist thanks to dedicated efforts by ERIC, the European Research Initiative on CLL, covering all test phases, from the pre-analytical and analytical to the post-analytical, pertaining to the analysis, interpretation, and reporting of the findings. That said, these recommendations apply to Sanger sequencing, which is increasingly being superseded by next generation sequencing (NGS), further underscoring the need for an update. Here, we present an overview of the clinical utility of immunogenetics in CLL and update our analytical recommendations with the aim to assist in the refined management of patients with CLL.
Bottom-up estimates of reactive nitrogen loss from Chinese wheat production in 2014
Authors: Tian Xingshuai , Yin Yulong , Zhuang Minghao , Cong Jiahui , Chu Yiyan , He Kai , Zhang Qingsong , Cui Zhenling
Published: May 2022

Excessive use of synthetic nitrogen (N) for Chinese wheat production results in high loss of reactive N loss (Nr; all forms of N except N2) into the environment, causing serious environmental issues. Quantifying Nr loss and its spatial variations therein is vital to optimize N management and mitigate loss. However, accurate, high spatial resolution estimations of Nr from wheat production are lacking due to limitations of data generation and estimation methods. Here, we applied the random forest (RF) algorithm to bottom-up N application rate data, obtained through a survey of millions of farmers, to estimate the Nr loss from wheat production in 2014. The results showed that the average total Nr loss was 52.5 kg N ha−1 (range: 4.6-157.8 kg N ha−1), which accounts for 26.1% of the total N applied. The hotspots for high Nr loss are the same as those high applied N, including northwestern Xinjiang, central-southern Hebei, Shandong, central-northern Jiangsu, and Hubei. Our database could guide regional N management and be used in conjunction with biogeochemical models.
VenomMaps: Updated species distribution maps and models for New World pitvipers (Viperidae: Crotalinae)
Authors: Rautsaw Rhett M. , Jiménez-Velázquez Gustavo , Hofmann Erich P. , Alencar Laura R. V. , Grünwald Christoph I. , Martins Marcio , Carrasco Paola , Doan Tiffany M. , Parkinson Christopher L.
Published: May 2022

Beyond providing critical information to biologists, species distributions are useful for naturalists, curious citizens, and applied disciplines including conservation planning and medical intervention. Venomous snakes are one group that highlight the importance of having accurate information given their cosmopolitan distribution and medical significance. Envenomation by snakebite is considered a neglected tropical disease by the World Health Organization and venomous snake distributions are used to assess vulnerability to snakebite based on species occurrence and antivenom/healthcare accessibility. However, recent studies highlighted the need for updated fine-scale distributions of venomous snakes. Pitvipers (Viperidae: Crotalinae) are responsible for >98% of snakebites in the New World. Therefore, to begin to address the need for updated fine-scale distributions, we created VenomMaps, a database and web application containing updated distribution maps and species distribution models for all species of New World pitvipers. With these distributions, biologists can better understand the biogeography and conservation status of this group, researchers can better assess vulnerability to snakebite, and medical professionals can easily discern species found in their area.
The effect of apigenin and chemotherapy combination treatments on apoptosis-related genes and proteins in acute leukaemia cell lines
Authors: Mahbub Amani A. , Le Maitre Christine L. , Cross Neil A. , Jordan-Mahy Nicola
Published: May 2022

Apigenin is a dietary polyphenol found abundantly in fruit and vegetables, which sensitizes leukaemia cells to topoisomerase inhibitor agents (e.g., etoposide), and alkylating agents (e.g., cyclophosphamide), reducing ATP levels and inducing apoptosis; whilst being protective to control haematopoietic stem cells. This study analysed the expression profiles of intrinsic and extrinsic apoptosis-related genes and proteins to help elucidate the mechanisms of action of apigenin when used in combination with etoposide or cyclophosphamide in lymphoid and myeloid leukaemia cell lines (Jurkat and THP-1). Expression of apoptosis-related genes were measured using a TaqMan® Human Apoptosis Array and the StepOne Plus RT-qPCR System, whilst apoptosis-related proteins were determined using a protein profiler™-human apoptosis array and the LI-COR OdysseyR Infrared Imaging System. Apigenin when combined with etoposide or cyclophosphamide-induced apoptosis via the mitochondrial pathway, increasing the expression of pro-apoptotic cytochrome c, SMAC/DIABLO, and HTRA2/OMI, which promoted caspase-9 and -3 activation. Targeting anti-apoptotic and/or pro-apoptotic members of the apoptotic pathways is a promising strategy to induce cancer cell death and improve sensitivity to chemotherapy agents. Here the apoptotic pathways induced by apigenin in combination with etoposide or cyclophosphamide were identified within human leukaemia cell lines, such applications could provide combination therapies for the treatment of leukaemia.
One material, many possibilities via enrichment of luminescence in La2Zr2O7:Tb3+ nanophosphors for forensic stimuli aided applications
Authors: Lavanya D. R. , Darshan G. P. , Malleshappa J. , Premkumar H. B. , Sharma S. C. , Hariprasad S. A. , Nagabhushana H.
Published: May 2022

Engineering a single material with multidirectional applications is crucial for improving productivity, low cost, flexibility, least power consumption, etc. To achieve these requirements, novel design structures and high-performance materials are in urgent need. Lanthanide-doped nanophosphors have the greatest strengths and ability in order to tune their applications in various dimensions. However, applications of nanophosphor in latent fingerprints visualization, anti-counterfeiting, and luminescent gels/films are still in their infancy. This study demonstrated a simple strategy to enhance the luminescence of Tb3+ (1–11 mol %) doped La2Zr2O7 nanophosphors by conjugating various fluxes via a simple solution combustion route. The photoluminescence emission spectra reveal intense peaks at ~ 491, 546, 587, and 622 nm, which arises from 5D4 → 7FJ (J = 6, 5, 4, 3) transitions of Tb3+ ions, respectively. The highest emission intensity was achieved in the NH4Cl flux assisted nanophosphor as compared to NaBr and NH4F assisted samples. The colorimetric images of fingerprints visualized using the optimized nanophosphor on forensic related surfaces exhibit level –III ridge details, including sweat pores, the width of the ridges, bifurcation angle, and the successive distance between sweat pores, etc. These results are decisive parameters that clearly support the statement “no two persons have ever been found to have the same fingerprints”. The anti-counterfeiting security ink was formulated using optimized nanophosphor and various patterns were designed by simple screen printing and dip pen technologies. The encoded information was decrypted only under ultraviolet 254 nm light. All the designed patterns are exhibit not just what it looks/feel like and how better it works. As a synergetic contribution of enhanced luminescence of the prepared nanophosphor, the green-emissive films were fabricated, which display excellent flexibility, uniformity, and transparency in the normal and ultraviolet 254 nm light illumination. The aforementioned results revealed that the prepared NH4Cl flux-assisted La2Zr2O7: Tb3+(7 mol %) NPs are considered to be the best candidate for multi-dimensional applications.
Tai Chi versus conventional exercise for improving cognitive function in older adults: a pilot randomized controlled trial
Authors: Yu Angus P. , Chin Edwin C. , Yu Danny J. , Fong Daniel Y. , Cheng Calvin P. , Hu Xiaoqing , Wei Gao X. , Siu Parco M.
Published: May 2022

Studies have shown that Tai Chi and conventional exercise can modify the brain through distinct mechanisms, resulting in different brain adaptations. Therefore, it is conceivable to speculate that these two exercise modalities may have different effects on improving cognitive function. This study was a parallel group, assessor-blinded, pilot randomized controlled trial comparing the effects of Tai Chi and conventional exercise on improving cognitive function in older persons with mild cognitive impairment (MCI). A total of 34 adults aged ≥ 50 years with MCI were randomized (1:1:1) to the Tai Chi group (TC,n = 10, 3 sessions of 60-min Yang-style Tai Chi training per week for 24 weeks), conventional exercise group (EX:n = 12, 3 sessions of 60-min fitness training per week for 24 weeks), or control group (CON:n = 12, no intervention). Global cognitive function assessed by the Hong Kong version of the Montreal Cognitive Assessment (MoCA-HK) and performance in various cognitive domains were examined at baseline, and 12 and 24 weeks of the intervention. Both exercise groups showed improved global cognitive function as measured by MoCA-HK compared with the control group after 12 and 24 weeks of the intervention, (allP < 0.001). Only TC achieved clinically relevant improvement on global cognitive function at week 12. Both exercise groups achieved clinically relevant improvements at the end of the interventions at week 24. Compared with EX, TC exhibited greater improvements on global cognitive function indicated by MoCA-HK after 12 weeks of the intervention (P < 0.001) and cognitive flexibility indicated by part B/A ratio score of the Trail Making Test throughout the study (allP < 0.05). Both interventions were equally effective in improving the other examined cognitive domains. Further studies are needed to substantiate the superior long-term benefits of Tai Chi on global cognitive function compared with conventional exercise, and dissect the underlying mechanisms of the two exercises on improving cognitive domains and the corresponding brain adaptations.

Trial registration: This study was registered at clinicaltrials.gov (Trial registration number: NCT04248400; first registration date: 30/01/2020).
EF-hand protein, EfhP, specifically binds Ca2+ and mediates Ca2+ regulation of virulence in a human pathogen Pseudomonas aeruginosa
Authors: Kayastha Biraj B. , Kubo Aya , Burch-Konda Jacob , Dohmen Rosalie L. , McCoy Jacee L. , Rogers Rendi R. , Mares Sergio , Bevere Justin , Huckaby Annalisa , Witt William , Peng Shuxia , Chaudhary Bharat , Mohanty Smita , Barbier Mariette , Cook Gabriel , Deng Junpeng , Patrauchan Marianna A.
Published: May 2022

Calcium (Ca2+) is well known as a second messenger in eukaryotes, where Ca2+signaling controls life-sustaining cellular processes. Although bacteria produce the components required for Ca2+signaling, little is known about the mechanisms of bacterial Ca2+signaling. Previously, we have identified a putative Ca2+-binding protein EfhP (PA4107) with two canonical EF-hand motifs and reported that EfhP mediates Ca2+regulation of virulence factors production and infectivity inPseudomonas aeruginosa,a human pathogen causing life-threatening infections. Here, we show that EfhP selectively binds Ca2+with 13.7 µM affinity, and that mutations at the +X and −Z positions within each or both EF-hand motifs abolished Ca2+binding. We also show that the hydrophobicity of EfhP increased in a Ca2+-dependent manner, however no such response was detected in the mutated proteins.15 N-NMR showed Ca2+-dependent chemical shifts in EfhP confirming Ca2+-binding triggered structural rearrangements in the protein. Deletion ofefhPimpairedP. aeruginosasurvival in macrophages and virulence in vivo.Disabling EfhP Ca2+binding abolished Ca2+induction of pyocyanin production in vitro. These data confirm that EfhP selectively binds Ca2+, which triggers its structural changes required for the Ca2+regulation ofP. aeruginosavirulence, thus establishing the role of EfhP as a Ca2+sensor.
Theoretically quantifying the direct and indirect benefits of vaccination against SARS-CoV-2 in terms of avoided deaths
Authors: Scutt Greg , Cross Mike , Waxman David
Published: May 2022

The Coronavirus Disease 2019 (COVID)-19 pandemic has placed unprecedented pressures on societies around the world. Successful vaccines, developed against the spike protein of the Severe Acute Respiratory Syndrome Virus 2 (SARS-CoV-2) virus, offer hope that new hospitalisations and new deaths will subside. However, vaccination takes place in a dynamic environment. For example, new variants of the disease may occur where the effectiveness of a vaccine lies below that of the original target of the vaccine, while changes in the behaviour of a population are accompanied by a changed basic reproduction number. Here, we aim to understand how changes in values of basic parameters affect the benefits of vaccination at the direct level, of the individuals vaccinated, and at the indirect level, of the wider, unvaccinated community. We work within the framework of a Susceptible-Infected-Recovered model, and produce a metric for the benefits of vaccination, at both direct and indirect levels, in terms of the number of avoided deaths. Taking into account the initial prevalence of a SARS-CoV-2 infection, the mortality rate of the disease, the basic reproduction number, the vaccination rate, and the effectiveness of a vaccine, we explore how these basic parameters affect the benefits of vaccination. We find a range of situations where indirect benefits of vaccination outweigh direct benefits. This especially occurs at lower rates of vaccination (20% – $$40\%$$

40
%

) and intermediate values of the basic reproduction number (1–1.5). The indirect benefits can be substantial, in some cases being more than 400% of the direct benefits. For an initial prevalence of SARS-CoV-2 infection of 2%, a basic reproduction number of 1.2, a mortality rate of 2%, and a vaccine effectiveness of 95%, our findings show, for a population of 500,000 people, where 100,000 susceptible individuals are vaccinated, that approximately 2200 deaths are avoided. However, approximately 600 of these deaths are avoided amongst vaccinated individuals, while approximately 1600 deaths are avoided in the wider, unvaccinated community.
NF90–NF45 is essential for β cell compensation under obesity-inducing metabolic stress through suppression of p53 signaling pathway
Authors: Lai Sylvia , Higuchi Takuma , Tsuda Masayuki , Sugiyama Yasunori , Morisawa Keiko , Taniguchi Taketoshi , Sakamoto Shuji
Published: May 2022

The Nuclear Factor 90 (NF90)–NF45 complex has been known to regulate the progression of transcription, mRNA stability, translational inhibition, RNA export and microRNA biogenesis. However, the physiological functions of the NF90–NF45 complex remain unclear. We newly discovered that the NF90–NF45 complex was expressed in primary β cells and established cell lines. Therefore, in this study, we focused on the function of the endogenous NF90–NF45 complex in the β cells. To investigate this issue, we generated β-cell-specific NF90–NF45 deficient mice. These mice exhibited hyperglycaemia and lower plasma insulin levels under a high fat diet together with decreased islet mass. To uncover this mechanism, we performed a whole-genome expression microarray of the total RNA prepared from β cell lines treated with siRNAs targeting both NF90 and NF45. In this result, we found an activation of p53 signaling in the NF90–NF45-knockdown cells. This activation was supported by elevation of luciferase activity derived from a reporter plasmid harboring p53 binding sites in the NF90–NF45-knockdown cells. Furthermore, the knockdown of NF90–NF45 resulted in a significant retardation of the β cell line growth rates. Importantly, a dominant negative form of p53 rescues the growth retardation in BTC6 cells depleted of NF90–NF45, suggesting that NF90–NF45 would be positively involved in β cell proliferation through suppression of p53 signal pathway. Taken together, NF90–NF45 is essential for β cell compensation under obesity-inducing metabolic stress via repression of p53 signaling.
Association between depression symptoms and moderately increased levels of the inflammation marker albuminuria is explained by age and comorbidity
Authors: Romundstad Solfrid , Hynnekleiv Torfinn
Published: May 2022

The study aimed to examine whether there are associations between depression symptoms and levels of the inflammation marker albuminuria. The 8303 participants in this cross-sectional study were subjects from the second survey of the Trøndelag Health Study (HUNT, Norway). Depression symptoms were assessed by the Hospital Anxiety and Depression Scale (HADS). Logistic regression analysis was performed to estimate the odds ratio (OR) for moderately increased albuminuria (ACR ≥ 3.0 mg/mmol) according to different HADS-depression (D) subgroups and -scores. Unadjusted ORs for moderately increased albuminuria were significantly increased in those with HADS-D ≥ 8 (OR 1.27, 95% CI 1.05–1.54, p = 0.013) and HADS-D ≥ 11 (OR 1.59, 95% CI 1.19–2.14, p = 0.002). After adjusting for age and sex, only HADS-D ≥ 11 was significantly associated with ACR ≥ 3.0 mg/mmol (OR 1.46, 95% CI 1.08–1.98, p = 0.014), and after multivariable adjustments for cardiovascular risk factors and comorbidity, there were no significant associations. However, adjusting for the interaction between age and HADS-D strengthened the association in linear regression models. The positive and significant association between moderately increased albuminuria and symptoms of depression found in unadjusted analyses weakened and disappeared after adjustments. Although individuals with depressive symptoms had albuminuria more often than individuals without such symptoms, and the association seemed to change with age, albuminuria may reflect other comorbidity and inflammation conditions than the depression symptomatology measured in this study.
Neural network-based prediction of the secret-key rate of quantum key distribution
Authors: Zhou Min-Gang , Liu Zhi-Ping , Liu Wen-Bo , Li Chen-Long , Bai Jun-Lin , Xue Yi-Ran , Fu Yao , Yin Hua-Lei , Chen Zeng-Bing
Published: May 2022

Numerical methods are widely used to calculate the secure key rate of many quantum key distribution protocols in practice, but they consume many computing resources and are too time-consuming. In this work, we take the homodyne detection discrete-modulated continuous-variable quantum key distribution (CV-QKD) as an example, and construct a neural network that can quickly predict the secure key rate based on the experimental parameters and experimental results. Compared to traditional numerical methods, the speed of the neural network is improved by several orders of magnitude. Importantly, the predicted key rates are not only highly accurate but also highly likely to be secure. This allows the secure key rate of discrete-modulated CV-QKD to be extracted in real time on a low-power platform. Furthermore, our method is versatile and can be extended to quickly calculate the complex secure key rates of various other unstructured quantum key distribution protocols.
Humans utilize sensory evidence of others’ intended action to make online decisions
Authors: Lokesh Rakshith , Sullivan Seth , Calalo Jan A. , Roth Adam , Swanik Brenden , Carter Michael J. , Cashaback Joshua G. A.
Published: May 2022

We often acquire sensory information from another person’s actions to make decisions on how to move, such as when walking through a crowded hallway. Past interactive decision-making research has focused on cognitive tasks that did not allow for sensory information exchange between humans prior to a decision. Here, we test the idea that humans accumulate sensory evidence of another person’s intended action to decide their own movement. In a competitive sensorimotor task, we show that humans exploit time to accumulate sensory evidence of another’s intended action and utilize this information to decide how to move. We captured this continuous interactive decision-making behaviour with a drift-diffusion model. Surprisingly, aligned with a ‘paralysis-by-analysis’ phenomenon, we found that humans often waited too long to accumulate sensory evidence and failed to make a decision. Understanding how humans engage in interactive and online decision-making has broad implications that spans sociology, athletics, interactive technology, and economics.
Remuscularization with triiodothyronine and β1-blocker therapy reverses post-ischemic left ventricular dysfunction and adverse remodeling
Authors: Bogush Nikolay , Tan Lin , Naqvi Emmen , Calvert John W. , Graham Robert M. , Taylor W. Robert , Naqvi Nawazish , Husain Ahsan
Published: May 2022

Renewal of the myocardium by preexisting cardiomyocytes is a powerful strategy for restoring the architecture and function of hearts injured by myocardial infarction. To advance this strategy, we show that combining two clinically approved drugs, but neither alone, muscularizes the heart through cardiomyocyte proliferation. Specifically, in adult murine cardiomyocytes, metoprolol, a cardioselective β1-adrenergic receptor blocker, when given with triiodothyronine (T3, a thyroid hormone) accentuates the ability of T3 to stimulate ERK1/2 phosphorylation and proliferative signaling by inhibiting expression of the nuclear phospho-ERK1/2-specific phosphatase, dual-specificity phosphatase-5. While short-duration metoprolol plus T3 therapy generates new heart muscle in healthy mice, in mice with myocardial infarction-induced left ventricular dysfunction and pathological remodeling, it remuscularizes the heart, restores contractile function and reverses chamber dilatation; outcomes that are enduring. If the beneficial effects of metoprolol plus T3 are replicated in humans, this therapeutic strategy has the potential to definitively address ischemic heart failure.
Allele expression biases in mixed-ploid sugarcane accessions
Authors: Correr Fernando Henrique , Furtado Agnelo , Franco Garcia Antonio Augusto , Henry Robert James , Rodrigues Alves Margarido Gabriel
Published: May 2022

Allele-specific expression (ASE) represents differences in the magnitude of expression between alleles of the same gene. This is not straightforward for polyploids, especially autopolyploids, as knowledge about the dose of each allele is required for accurate estimation of ASE. This is the case for the genomically complex Saccharum species, characterized by high levels of ploidy and aneuploidy. We used a Beta-Binomial model to test for allelic imbalance in Saccharum, with adaptations for mixed-ploid organisms. The hierarchical Beta-Binomial model was used to test if allele expression followed the expectation based on genomic allele dosage. The highest frequencies of ASE occurred in sugarcane hybrids, suggesting a possible influence of interspecific hybridization in these genotypes. For all accessions, genes showing ASE (ASEGs) were less frequent than those with balanced allelic expression. These genes were related to a broad range of processes, mostly associated with general metabolism, organelles, responses to stress and responses to stimuli. In addition, the frequency of ASEGs in high-level functional terms was similar among the genotypes, with a few genes associated with more specific biological processes. We hypothesize that ASE in Saccharum is largely a genotype-specific phenomenon, as a large number of ASEGs were exclusive to individual accessions.
How social/environmental determinants and inflammation affect salivary telomere length among middle-older adults in the health and retirement study
Authors: Courtney Margaret Gough , Roberts Josephine , Godde Kanya
Published: May 2022

Social epidemiology posits that chronic stress from social determinants will lead to a prolonged inflammatory response that may induce accelerated aging as measured, for example, through telomere length (TL). In this paper, we hypothesize variables across demographic, health-related, and contextual/environmental domains influence the body’s stress response, increase inflammation (as measured through high-sensitivity C-reactive protein (hs-CRP)), and thereby lead to shortening of telomeres. This population-based research uses data from the 2008 Health and Retirement Study on participants ages ≤ 54–95 + years, estimating logistic regression and Cox proportional hazards models of variables (with and without confounders) across the domains on shortened TL. A mediation analysis is also conducted. Contrary to expectations, hs-CRP is not associated with risk of shortened TL. Rather, factors related to accessing health care, underlying conditions of frailty, and social inequality appear to predict risk of shorter TL, and models demonstrate considerable confounding. Further, hs-CRP is not a mediator for TL. Therefore, the social determinants of health examined do not appear to follow an inflammatory pathway for shortened TL. The finding of a relationship to social determinants affecting access to health care and medical conditions underscores the need to address social determinants alongside primary care when examining health inequities.
Genome-wide identification of copy number variation and association with fat deposition in thin and fat-tailed sheep breeds
Authors: Taghizadeh Shadan , Gholizadeh Mohsen , rahimi-Mianji Ghodrat , Moradi Mohammad Hossein , Costilla Roy , Moore Stephen , Di Gerlando Rosalia
Published: May 2022

Copy number variants (CNVs) are a type of genetic polymorphism which contribute to phenotypic variation in several species, including livestock. In this study, we used genomic data of 192 animals from 3 Iranian sheep breeds including 96 Baluchi sheep and 47 Lori-Bakhtiari sheep as fat-tailed breeds and 47 Zel sheep as thin-tailed sheep breed genotyped with Illumina OvineSNP50K Beadchip arrays. Also, for association test, 70 samples of Valle del Belice sheep were added to the association test as thin-tailed sheep breed. PennCNV and CNVRuler software were, respectively, used to study the copy number variation and genomic association analyses. We detected 573 and 242 CNVs in the fat and thin tailed breeds, respectively. In terms of CNV regions (CNVRs), these represented 328 and 187 CNVRs that were within or overlapping with 790 known Ovine genes. The CNVRs covered approximately 73.85 Mb of the sheep genome with average length 146.88 kb, and corresponded to 2.6% of the autosomal genome sequence. Five CNVRs were randomly chosen for validation, of which 4 were experimentally confirmed using Real time qPCR. Functional enrichment analysis showed that genes harbouring CNVs in thin-tailed sheep were involved in the adaptive immune response, regulation of reactive oxygen species biosynthetic process and response to starvation. In fat-tailed breeds these genes were involved in cellular protein modification process, regulation of heart rate, intestinal absorption, olfactory receptor activity and ATP binding. Association test identified one copy gained CNVR on chromosomes 6 harbouring two protein-coding genes HGFAC and LRPAP1. Our findings provide information about genomic structural changes and their association to the interested traits including fat deposition and environmental compatibility in sheep.
Effects of broad-spectrum antibiotics on the colonisation of probiotic yeast Saccharomyces boulardii in the murine gastrointestinal tract
Authors: Hedin Karl Alex , Rees Vanessa Emily , Zhang Hongbin , Kruse Vibeke , Vazquez-Uribe Ruben , Sommer Morten Otto Alexander
Published: May 2022

Mouse models are commonly used to study the colonisation profiles of microorganisms introduced to the gastrointestinal tract. Three commonly used mouse models include conventional, germ-free, and antibiotic-treated mice. However, colonisation resistance in conventional mice and specialised equipment for germ-free mice are usually limiting factors in their applications. In this study, we sought to establish a robust colonisation model for Saccharomyces boulardii, a probiotic yeast that has caught attention in the field of probiotics and advanced microbiome therapeutics. We characterised the colonisation of S. boulardii in conventional mice and mice treated with a cocktail of broad-spectrum antibiotics, including ampicillin, kanamycin, metronidazole and vancomycin. We found colonisation levels increased up to 10,000-fold in the antibiotic-treated mice compared to nonantibiotic-treated mice. Furthermore, S. boulardii was detected continuously in more than 75% of mice for 10 days after the last administration in antibiotic-treated mice, in contrast to in nonantibiotic-treated mice where S. boulardii was undetectable in less than 2 days. Finally, we demonstrated that this antibiotic cocktail can be used in two commonly used mouse strains, C57BL/6 and ob/ob mice, both achieving ~ 108 CFU/g of S. boulardii in faeces. These findings highlight that the antibiotic cocktail used in this study is an advantageous tool to study S. boulardii based probiotic and advanced microbiome therapeutics.
Heart rate variability comparison between young males after 4–6 weeks from the end of SARS-CoV-2 infection and controls
Authors: Soliński Mateusz , Pawlak Agnieszka , Petelczyc Monika , Buchner Teodor , Aftyka Joanna , Gil Robert , Król Zbigniew J. , Żebrowski Jan J.
Published: May 2022

Due to the prolonged inflammatory process induced by infection of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), indices of autonomic nervous system dysfunction may persist long after viral shedding. Previous studies showed significant changes in HRV parameters in severe (including fatal) infection of SARS-CoV-2. However, few studies have comprehensively examined HRV in individuals who previously presented as asymptomatic or mildly symptomatic cases of COVID-19. In this study, we examined HRV in asymptomatic or mildly symptomatic individuals 5–7 weeks following positive confirmation of SARS-CoV-2 infection. Sixty-five ECG Holter recordings from young (mean age 22.6 ± 3.4 years), physically fit male subjects 4–6 weeks after the second negative test (considered to be the start of recovery) and twenty-six control male subjects (mean age 23.2 ± 2.9 years) were considered in the study. Night-time RR time series were extracted from ECG signals. Selected linear as well as nonlinear HRV parameters were calculated. We found significant differences in Porta’s symbolic analysis parameters V0 and V2 (p < 0.001), α2(p < 0.001), very low-frequency component (VLF;p = 0.022) and respiratory peak (from the PRSA method;p = 0.012). These differences may be caused by the changes of activity of the parasympathetic autonomic nervous system as well as by the coupling of respiratory rhythm with heart rate due to an increase in pulmonary arterial vascular resistance. The results suggest that the differences with the control group in the HRV parameters, that reflect the functional state of the autonomic nervous system, are measurable after a few weeks from the beginning of the recovery even in the post-COVID group—a young and physically active population. We indicate HRV sensitive markers which may be used in long-term monitoring of patients after recovery.
Effects of separated pair housing of female C57BL/6JRj mice on well-being
Authors: Hohlbaum K. , Merle R. , Frahm S. , Rex A. , Palme R. , Thöne-Reineke C. , Ullmann K.
Published: May 2022

In laboratory animal facilities, it is a common code of practice to house female mice in groups. However, some experimental conditions require to house them individually, even though social isolation may impair their well-being. Therefore, we introduced a separated pair housing system and investigated whether it can refine single housing of adult female C57BL/6JRj mice. Individually ventilated cages (IVC) were divided by perforated transparent walls to separate two mice within a cage. The cage divider allowed visual, acoustic, and olfactory contact between the mice but prevented interindividual body-contact or food sharing. Short- and long-term effects of the separated pair housing system on the well-being of the mice were compared with single and group housing using a range of behavioral and physiological parameters: Nest building behavior was assessed based on the complexity of nests, the burrowing performance was measured by the amount of food pellets removed from a bottle, and trait anxiety-related behavior was tested in the free exploratory paradigm. For the evaluation of the ease of handling, interaction with the experimenter's hand was monitored. Social interaction with unknown conspecifics and locomotor activity were investigated in a test arena. Moreover, body weight and stress hormone (metabolites) were measured in feces and hair. After the mice spent a day under the respective housing conditions, concentrations of fecal corticosterone metabolites were higher in separated pair-housed mice, and they built nests of a higher complexity when compared to single-housed mice. The latter effect was still observable eight weeks later. In week 8, separated pair-housed mice showed less locomotor activity in the social interaction arena compared to mice from the other housing systems, i.e., single and group housing. Regardless of the time of testing, pair housing improved the burrowing performance. Separated pair-housed mice were more difficult to catch than group-housed mice. Hair corticosterone, progesterone, and dehydroepiandrosterone concentrations changed with increasing age independently of the housing system. There were no effects of the housing systems on trait anxiety-related behavior in the free exploratory paradigm, voluntary interaction with the experimenter’s hand, and body weight. Overall, the transfer to the separated pair housing system caused short-term stress responses in female C57BL/6JRj mice. Long-term effects of separated pair housing were ambiguous. On one hand, separated pair housing increased nesting and burrowing behavior and may therefore be beneficial compared to single housing. But on the other hand, locomotor activity decreased. The study underlined that the effects of the housing conditions on physiological and behavioral parameters should be considered when analyzing and reporting animal experiments.
The role of polymeric chains as a protective environment for improving the stability and efficiency of fluorogenic peptide substrates
Authors: Arnaiz Ana , Guembe-García Marta , Delgado-Pinar Estefanía , Valente Artur J. M. , Ibeas Saturnino , García José M. , Vallejos Saúl
Published: May 2022

We have faced the preparation of fully water-soluble fluorescent peptide substrate with long-term environmental stability (in solution more than 35 weeks) and, accordingly, with stable results in the use of this probe in determining the activity of enzymes. We have achieved this goal by preparing a co-polymer of the commercial N-vinyl-2-pyrrolidone (99.5% mol) and a fluorescent substrate for trypsin activity determination having a vinylic group (0.5%). The activity of trypsin has been measured in water solutions of this polymer over time, contrasted against the activity of both the commercial substrate Z-L-Arg-7-amido-4-methylcoumarin hydrochloride and its monomeric derivative, prepared ad-hoc. Initially, the activity of the sensory polymer was 74.53 ± 1.72 nmol/min/mg of enzyme, while that of the commercial substrate was 20.44 ± 0.65 nmol/min/mg of enzyme, the former maintained stable along weeks and the latter with a deep decay to zero in three weeks. The ‘protection’ effect exerted by the polymer chain has been studied by solvation studies by UV–Vis spectroscopy, steady-state & time resolved fluorescence, thermogravimetry and isothermal titration calorimetry.
A comprehensive evaluation of COVID-19 policies and outcomes in 50 countries and territories
Authors: Tsou Hsiao-Hui , Kuo Shu-Chen , Lin Yu-Hsuan , Hsiung Chao A. , Chiou Hung-Yi , Chen Wei J. , Wu Shiow-Ing , Sytwu Huey-Kang , Chen Pau-Chung , Wu Meng-Hsuan , Hsu Ya-Ting , Wu Hsiao-Yu , Lee Fang-Jing , Shih Shu-Man , Liu Ding-Ping , Chang Shan-Chwen
Published: May 2022

The COVID-19 pandemic struck the world unguarded, some places outperformed others in COVID-19 containment. This longitudinal study considered a comparative evaluation of COVID-19 containment across 50 distinctly governed regions between March 2020 and November 2021. Our analysis distinguishes between a pre-vaccine phase (March–November 2020) and a vaccinating phase (December 2020–November 2021). In the first phase, we develop an indicator, termed lockdown efficiency (LE), to estimate the efficacy of measures against monthly case numbers. Nine other indicators were considered, including vaccine-related indicators in the second phase. Linear mixed models are used to explore the relationship between each government policy & hygiene education (GP&HE) indicator and each vital health & socioeconomic (VH&SE) measure. Our ranking shows that surveyed countries in Oceania and Asian outperformed countries in other regions for pandemic containment prior to vaccine development. Their success appears to be associated with non-pharmaceutical interventions, acting early, and adjusting policies as needed. After vaccines have been distributed, maintaining non-pharmacological intervention is the best way to achieve protection from variant viral strains, breakthrough infections, waning vaccine efficacy, and vaccine hesitancy limiting of herd immunity. The findings of the study provide insights into the effectiveness of emerging infectious disease containment policies worldwide.
Establishment of apiary-level risk of American foulbrood through the detection of Paenibacillus larvae spores in pooled, extracted honey in Saskatchewan
Authors: Zabrodski Michael W. , Epp Tasha , Wilson Geoff , Moshynskyy Igor , Sharafi Mohsen , Reitsma Lara , Castano Ospina Mateo , DeBruyne Jessica E. , Wentzell Alexandra , Wood Sarah C. , Kozii Ivanna V. , Klein Colby D. , Thebeau Jenna , Sobchishin LaRhonda , Ruzzini Antonio C. , Simko Elemir
Published: May 2022

Paenibacillus larvae, the causative agent of American foulbrood (AFB), produces spores that may be detectable within honey. We analyzed the spore content of pooled, extracted honey from 52 large-scale (L) and 64 small-scale (S) Saskatchewan beekeepers over a two-year period (2019–2020). Our objectives were: (i) establish reliable prognostic reference ranges for spore concentrations in extracted honey to determine future AFB risk at the apiary level; (ii) identify management practices as targets for mitigation of risk. P. larvae spores were detected in 753 of 1476 samples (51%). Beekeepers were stratified into low (< 2 spores/gram), moderate (2- < 100 spores/gram), and high (≥ 100 spores/gram) risk categories. Of forty-nine L beekeepers sampled in 2019, those that reported AFB in 2020 included 0/26 low, 3/18 moderate, and 3/5 high risk. Of twenty-seven L beekeepers sampled in 2020, those that reported AFB in 2021 included 0/11 low, 2/14 moderate, and 1/2 high risk. Predictive modelling included indoor overwintering of hives, purchase of used equipment, movement of honey-producing colonies between apiaries, beekeeper demographic, and antimicrobial use as risk category predictors. Saskatchewan beekeepers with fewer than 2 spores/gram in extracted honey that avoid high risk activities may be considered at low risk of AFB the following year.
Comprehensive Analysis of Prognostic and immune infiltrates for FOXPs Transcription Factors in Human Breast Cancer
Authors: Yi Jianing , Tan Siyi , Zeng Yuanjun , Zou Lianhong , Zeng Jie , Zhang Chaojie , Liu Luyao , Fan Peizhi
Published: May 2022

Forkhead-box-P family include FOXP1/2/3/4 and its clinical significance still remains unclear in breast cancer (BRCA). We analysed the expressions of FOXPs in BRCA patients to determine diagnostic and prognostic values. Our results indicated that the transcriptional levels of FOXP3/4 were up-regulated in BRCA patients, but FOXP2 were down-regulated. No statistically significant correlation were found between the expression levels of FOXPs in Pathologic stage. FOXP2/3 had a significantly high AUC value in the detection of breast cancer, with 96.8% or 95.7% in accuracy respectively. Our study also suggested that BRCA patients with high transcription levels of FOXP1/2/4 were significantly associated with longer Overall Survival (OS). In contrast, BRCA patients with high transcription level of FOXP3 was not statistically related with OS. Our work revealed that FOXPs were closely related to the alteration of extensive immune checkpoints in breast invasive carcinoma. Additionally, FOXP3 has a significant positive correlation with PDCD1, CD274, CTLA4 and TMB in breast cancer, and FOXP3 expression showed a statistically significant correlation with infiltration of immune cells. Finally, we found that FOXP3 expression predicted the breast cancer cells response to anticancer drugs. Altogether, our work strongly suggested that FOXPs could serve as a biomarker for tumor detection, therapeutic design and prognosis.
Agreements between mean arterial pressure from radial and femoral artery measurements in refractory shock patients
Authors: Wisanusattra Hemmawan , Khwannimit Bodin
Published: May 2022

Radial and femoral artery catheterization is the most common procedure for monitoring patients with shock. However, a disagreement in mean arterial pressure (MAP) between the two sites has been reported. Hence, the aim of this study was to compare the MAP from the radial artery (MAPradial) with that of the femoral artery (MAPfemoral) in patients with refractory shock. A prospective study was conducted in the medical intensive care unit. The radial and femoral were simultaneously measured MAP in the patients every hour, for 24 h. In total, 706 paired data points were obtained from 32 patients. MAPradial strongly correlated with MAPfemoral (r = 0.89, p < 0.0001). However, overall MAPradial was significantly lower than MAPfemoral 7.6 mmHg. The bias between MAPradial and MAPfemoral was − 7.6 mmHg (95% limits of agreement (LOA), − 24.1 to 8.9). In the subgroup of patients with MAPradial < 65 mmHg, MAPradial moderately correlated with MAPfemoral (r = 0.63) and the bias was increased to − 13.0 mmHg (95% LOA, − 28.8 to 2.9). There were 414 (58.6%) measurements in which the MAP gradient between the two sites was > 5 mmHg. In conclusion, the radial artery significantly underestimated MAP compared with the femoral artery in patients with refractory shock.