bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacovigilance study of the association between dipeptidyl peptidase–4 inhibitors and angioedema using the FDA Adverse Event Reporting System (FAERS)
Authors: Ohyama Katsuhiro , Shindo Junichiro , Takahashi Tomohiro , Takeuchi Hironori , Hori Yusuke
Published: July 2022

Dipeptidyl peptidase-4 (DPP-4) plays a minor role in degrading vasoactive peptides that cause angioedema when angiotensin-converting enzyme (ACE) is present and fully functional. This study investigated the association between DPP-4 inhibitors (DPP-4Is) and angioedema, including cases where the concomitant use of ACE inhibitors (ACEIs) was absent. We obtained data from the US Food and Drug Administration Adverse Event Reporting System and performed a disproportionality analysis, using the reporting odds ratio (ROR) and information component (IC) for signal detection in patients aged ≥ 40 years, stratified by age group and sex. No signal was detected for DPP-4Is when the entire dataset was analyzed. However, a signal was detected for the entire female subset group, the three stratified female groups aged ≥ 60 years, and males in their 40 s. After excluding the data of concomitant ACEI users, most ROR and IC values were lower and significant only for females in their 60 s and males aged ≥ 80 years. Regarding individual DPP-4Is signals, those detected for saxagliptin and sitagliptin in some age groups disappeared after excluding the data of ACEI users. Notably, linagliptin was the only DPP-4I where signals were detected in most female groups, regardless of age and without concomitant ACEI use. Our findings suggest that some DPP-4Is were associated with a higher reporting of angioedema as per age and sex, even in the absence of concomitant ACEI use.
Annealing effect of thermotropic liquid crystalline copolyester fibers on thermo-mechanical properties and morphology
Authors: Park Sanghyeon , Na Yeji , Kim A Young , Kwac Lee Ku , Kim Hong Gun , Chang Jin-Hae
Published: July 2022

A series of thermotropic liquid crystal copolyesters (Co-TLCPs) was prepared by melt polymerization using 2,5-diethoxyterephthalic acid (DTA), 2,7-dihydroxynaphthalene (DHN), and p-hydroxybenzoic acid (HBA) monomers, where the HBA content was varied (0–5 mol). At 3 mol HBA, the Co-TLCPs formed nematic mesophases, while below this concentration, the liquid crystalline phase did not appear. The Co-TLCP sample with 3 mol HBA was subjected to melt spinning and heat-treated under various conditions (temperature and time) to investigate their effect on the thermo–mechanical properties and degree of crystallinity. The objective was to determine the critical heat treatment condition that can maximize the properties of the spun Co-TLCP fibers. The microstructure of the heat-treated fiber was investigated using scanning electron microscopy, and the optimal annealing conditions were confirmed based on the morphology of the fiber, which exhibited a skin–core structure owing to the varying heat and pressure conditions applied during spinning.
Development a novel robust method to enhance the solubility of Oxaprozin as nonsteroidal anti-inflammatory drug based on machine-learning
Authors: Abdelbasset Walid Kamal , Elkholi Safaa M. , Ismail Khadiga Ahmed , Alshehri Sameer , Alobaida Ahmed , Huwaimel Bader , Alatawi Ahmed D. , Alsubaiyel Amal M. , Venkatesan Kumar , Abourehab Mohammed A. S.
Published: July 2022

Accurate specification of the drugs’ solubility is known as an important activity to appropriately manage the supercritical impregnation process. Over the last decades, the application of supercritical fluids (SCFs), mainly CO2, has found great interest as a promising solution to dominate the limitations of traditional methods including high toxicity, difficulty of control, high expense and low stability. Oxaprozin is an efficient off-patent nonsteroidal anti-inflammatory drug (NSAID), which is being extensively used for the pain management of patients suffering from chronic musculoskeletal disorders such as rheumatoid arthritis. In this paper, the prominent purpose of the authors is to predict and consequently optimize the solubility of Oxaprozin inside the CO2SCF. To do this, the authors employed two basic models and improved them with the Adaboost ensemble method. The base models include Gaussian process regression (GPR) and decision tree (DT). We optimized and evaluated the hyper-parameters of them using standard metrics. Boosted DT has an MAE error rate, an R2-score, and an MAPE of 6.806E-05, 0.980, and 4.511E-01, respectively. Also, boosted GPR has an R2-score of 0.998 and its MAPE error is 3.929E-02, and with MAE it has an error rate of 5.024E-06. So, boosted GPR was chosen as the best model, and the best values were: (T = 3.38E + 02, P = 4.0E + 02, Solubility = 0.001241).
Coculturing of Mucor plumbeus and Bacillus subtilis bacterium as an efficient fermentation strategy to enhance fungal lipid and gamma-linolenic acid (GLA) production
Authors: Mohamed Hassan , Awad Mohamed F. , Shah Aabid Manzoor , Sadaqat Beenish , Nazir Yusuf , Naz Tahira , Yang Wu , Song Yuanda
Published: July 2022

This study aimed to improve lipid and gamma-linolenic acid (GLA) production of an oleaginous fungus, Mucor plumbeus, through coculturing with Bacillus subtilis bacteria, optimising the environmental and nutritional culture conditions, and scaling them for batch fermentation. The maximum levels of biomass, lipid, fatty acid, and GLA in a 5 L bioreactor containing cellobiose and ammonium sulfate as the optimal carbon and nitrogen sources, respectively, achieved during the coculturing processes were 14.5 ± 0.4 g/L, 41.5 ± 1.3, 24 ± 0.8, and 20 ± 0.5%, respectively. This strategy uses cellobiose in place of glucose, decreasing production costs. The nutritional and abiotic factor results suggest that the highest production efficiency is achieved at 6.5 pH, 30 °C temperature, 10% (v/v) inoculum composition, 200 rpm agitation speed, and a 5-day incubation period. Interestingly, the GLA concentration of cocultures (20.0 ± 0.5%) was twofold higher than that of monocultures (8.27 ± 0.11%). More importantly, the GC chromatograms of cocultures indicated the presence of one additional peak corresponding to decanoic acid (5.32 ± 0.20%) that is absent in monocultures, indicating activation of silent gene clusters via cocultivation with bacteria. This study is the first to show that coculturing of Mucor plumbeus with Bacillus subtilis is a promising strategy with industrialisation potential for the production of GLA-rich microbial lipids and prospective biosynthesis of new products.
Global slowness and increased intra-individual variability are key features of attentional deficits and cognitive fluctuations in post COVID-19 patients
Authors: Ortelli Paola , Benso Francesco , Ferrazzoli Davide , Scarano Ilaria , Saltuari Leopold , Sebastianelli Luca , Versace Viviana , Maestri Roberto
Published: July 2022

Fatigue, attentional deficits and cognitive fluctuations are the most characterizing symptoms of neurological involvement in Post COVID-19 syndrome (PCS). As the intraindividual variability (IIV) in cognitive performances has been recognized as a hallmark of brain-related disorders associated with cognitive deficits, it could be an interesting measure to elucidate the mechanisms subtending both the attentive impairment and the cognitive fluctuations in these patients. By referring to IIV analysis of Reaction Times (RTs), the present study aims to define the attentive impairment and its relation to fluctuations and fatigue, in patients suffering from Post COVID-19 neurological symptoms. 74 patients were enrolled. They underwent an extensive clinical and neuropsychological assessments, as well as computerized Sustained Attention and Stroop tasks. For studying IIV, RTs distributions of performances in computerized tasks were fitted with ex-Gaussian distribution, for obtaining the τ values. Finally, the Resting Motor Threshold (RMT) was also collected to estimate cortical excitability. 29 healthy volunteers served as controls. Patients showed poorer scores in Montreal Cognitive Assessment and higher RMT, in comparison with controls. In Sustained Attention Task, Mean, µ, σ and τ values were significantly higher in PCS patients (p value =  < 0.0001; 0.001; 0.018 and < 0.0001, respectively). Repeated measures ANOVA comparing the RTs mean in Stroop task within-subject and between-subjects revealed significant condition and group effect (p < 0.0001 both) and significant interaction (p = 0.005), indicating worst performances in patients. The mean of the derived interference value was significantly higher in PCS patients than in controls (p = 0.036). Patients suffering from PCS show deficits in attention, both in the sustained and executive components. Both high RTs means and high IIV subtend these deficits and could explain the often-complained cognitive fluctuations in this population.
(+)-Usnic acid and its salts, inhibitors of SARS‐CoV‐2, identified by using in silico methods and in vitro assay
Authors: Oh Eunseok , Wang Weihong , Park Kyu-Hyung , Park Chanyoon , Cho Youbin , Lee JunI , Kang Eunmo , Kang Heonjoong
Published: July 2022

The pandemic caused by severe acute respiratory Coronavirus-2 (SARS-CoV-2) has been ongoing for over two years, and treatment for COVID-19, other than monoclonal antibodies, is urgently required. Accordingly, we have investigated the inhibitors of SARS-CoV-2 protein targets by high-throughput virtual screening using a marine natural products database. Considering the calculated molecular properties and availability of the compounds, (+)-usnic acid was selected as a suitable hit. In the in vitro antiviral assay of (+)-usnic acid by the immunofluorescence method, IC50 was 7.99 μM, which is similar to that of remdesivir used as a positive control. The generalized Born and surface area continuum solvation (MM/GBSA) method was performed to find the potent target of (+)-usnic acid, and the Mpro protein showed the most prominent value, −52.05 kcal/mol, among other SARS-CoV-2 protein targets. Thereafter, RMSD and protein–ligand interactions were profiled using molecular dynamics (MD) simulations. Sodium usnate (NaU) improved in vitro assay results with an IC50 of 5.33 μM and a selectivity index (SI) of 9.38. Additionally, when (+)-usnic acid was assayed against SARS-CoV-2 variants, it showed enhanced efficacy toward beta variants with an IC50 of 2.92 μM and SI of 11.1. We report the in vitro anti-SARS-CoV-2 efficacy of (+)-usnic acid in this study and propose that it has the potential to be developed as a COVID-19 treatment if its in vivo efficacy has been confirmed.
Localization-adjusted diagnostic performance and assistance effect of a computer-aided detection system for pneumothorax and consolidation
Authors: Lee Sun Yeop , Ha Sangwoo , Jeon Min Gyeong , Li Hao , Choi Hyunju , Kim Hwa Pyung , Choi Ye Ra , I Hoseok , Jeong Yeon Joo , Park Yoon Ha , Ahn Hyemin , Hong Sang Hyup , Koo Hyun Jung , Lee Choong Wook , Kim Min Jae , Kim Yeon Joo , Kim Kyung Won , Choi Jong Mun
Published: July 2022

While many deep-learning-based computer-aided detection systems (CAD) have been developed and commercialized for abnormality detection in chest radiographs (CXR), their ability to localize a target abnormality is rarely reported. Localization accuracy is important in terms of model interpretability, which is crucial in clinical settings. Moreover, diagnostic performances are likely to vary depending on thresholds which define an accurate localization. In a multi-center, stand-alone clinical trial using temporal and external validation datasets of 1,050 CXRs, we evaluated localization accuracy, localization-adjusted discrimination, and calibration of a commercially available deep-learning-based CAD for detecting consolidation and pneumothorax. The CAD achieved image-level AUROC (95% CI) of 0.960 (0.945, 0.975), sensitivity of 0.933 (0.899, 0.959), specificity of 0.948 (0.930, 0.963), dice of 0.691 (0.664, 0.718), moderate calibration for consolidation, and image-level AUROC of 0.978 (0.965, 0.991), sensitivity of 0.956 (0.923, 0.978), specificity of 0.996 (0.989, 0.999), dice of 0.798 (0.770, 0.826), moderate calibration for pneumothorax. Diagnostic performances varied substantially when localization accuracy was accounted for but remained high at the minimum threshold of clinical relevance. In a separate trial for diagnostic impact using 461 CXRs, the causal effect of the CAD assistance on clinicians’ diagnostic performances was estimated. After adjusting for age, sex, dataset, and abnormality type, the CAD improved clinicians’ diagnostic performances on average (OR [95% CI] = 1.73 [1.30, 2.32]; p < 0.001), although the effects varied substantially by clinical backgrounds. The CAD was found to have high stand-alone diagnostic performances and may beneficially impact clinicians’ diagnostic performances when used in clinical settings.
Proteome and phosphoproteome signatures of recurrence for HPV+ head and neck squamous cell carcinoma
Authors: Kaneko Tomonori , Zeng Peter Y. F. , Liu Xuguang , Abdo Rober , Barrett John W. , Zhang Qi , Nichols Anthony C. , Li Shawn Shun-Cheng
Published: July 2022

Background

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and the human papillomavirus (HPV+)-driven subtype is the fastest rising cancer in North America. Although most cases of HPV+ HNSCC respond favorably to the treatment via surgery followed by radiochemotherapy, up to 20% recur with a poor prognosis. The molecular and cellular mechanisms of recurrence are not fully understood.

Methods

To gain insights into the mechanisms of recurrence and to inform patient stratification and personalized treatment, we compared the proteome and phosphoproteome of recurrent and non-recurrent tumors by quantitative mass spectrometry.

Results

We observe significant differences between the recurrent and non-recurrent tumors in cellular composition, function, and signaling. The recurrent tumors are characterized by a pro-fibrotic and immunosuppressive tumor microenvironment (TME) featuring markedly more abundant cancer-associated fibroblasts, extracellular matrix (ECM), neutrophils, and suppressive myeloid cells. Defective T cell function and increased epithelial-mesenchymal transition potential are also associated with recurrence. These cellular changes in the TME are accompanied by reprogramming of the kinome and the signaling networks that regulate the ECM, cytoskeletal reorganization, cell adhesion, neutrophil function, and coagulation.

Conclusions

In addition to providing systems-level insights into the molecular basis of recurrence, our work identifies numerous mechanism-based, candidate biomarkers and therapeutic targets that may aid future endeavors to develop prognostic biomarkers and precision-targeted treatment for recurrent HPV+ HNSCC.
Reaction-intermediate-induced atomic mobility in heterogeneous metal catalysts for electrochemical reduction of CO2
Authors: Li Feng , Zhou Ce , Feygin Eliana , Roy Pierre-Nicholas , Chen Leanne D. , Klinkova Anna
Published: July 2022

In contrast to activity and selectivity, the stability trends in heterogeneous metal electrocatalysts used for CO2 electroreduction remain less understood; here, we systematically study the effect of reaction intermediates on the catalyst stability.
Catalytic selective hydrogenation of acetic acid to acetaldehyde over the surface of the iron shell on Pd–Fe alloy nanoparticles
Authors: Hosokawa Saburo , Fukuzumi Noriyuki , Nakatani Tetsu , Honma Tetsuo , Mizugaki Tomoo , Tanaka Tsunehiro , Wada Kenji
Published: July 2022

The Fe metal shell on Pd–Fe alloy nanoparticles formed by strong metal–support interaction (SMSI) promotes catalytic selective hydrogenation from acetic acid to acetaldehyde.
Ni(i)–TPA stabilization by hydrogen bond formation on the second coordination sphere: a DFT characterization
Authors: Posada-Pérez Sergio , Escayola Silvia , Poater Jordi , Solà Miquel , Poater Albert
Published: July 2022

We have characterized the Ni(i)– and Ni(ii)–TPA complexes and analyzed the role of hydrogen bonding in the stability of Ni(i)–TPA complexes. Our results prove the important contribution of hydrogen bonding in the stability of TPA–Ni(i)–F complexes.
Surface composition of size-selected sea salt particles under the influence of organic acids studied in situ using synchrotron radiation X-ray photoelectron spectroscopy
Authors: Patanen Minna , Unger Isaak , Saak Clara-Magdalena , Gopakumar Geethanjali , Lexelius Rebecka , Björneholm Olle , Salter Matthew , Zieger Paul
Published: July 2022

Synchrotron X-ray photoelectron spectroscopic surface characterisation of size-resolved sea salt aerosol particles revealed Mg enrichment in the particle surface layer which was either enhanced or decreased depending on the organic compound added.
Green-light-emitting carbon dots via eco-friendly route and their potential in ferric-ion detection and WLEDs
Authors: Qiu Hanxun , Yuan Fangyu , Wang Yuanchi , Zhang Zheng , Li Jing , Li Ying
Published: July 2022

Green fluorescent carbon dots (G-CDs) have been achieved via an eco-friendly microwave-assisted solvent-free approach. The low cost, simplicity of operation, good controllability and favorable fluorescence performance endow G-CDs with great potential in ion-detection chemical sensors and high-performance light-emitting devices.
Synthesis and biological evaluation of paeoveitol D derivatives as new melatonin receptor agonists with antidepressant activities
Authors: Li Tian-Ze , Hu Jing , Sun Jin-Jin , Huang Xiao-Yan , Geng Chang-An , Liu Shu-Bai , Zhang Xue-Mei , Chen Ji-Jun
Published: July 2022

Paeoveitol D derivatives were synthesized as potent MT1 and MT2 receptors agonists with in vivo antidepressant activity.
Ruthenium-catalyzed diazoacetate/cyclooctene metathesis copolymerization
Authors: Ji Minghang , Zheng Shengquan , Zou Chen , Chen Min
Published: July 2022

As a powerful synthetic tool, ruthenium-catalyzed ring-opening metathesis polymerization (ROMP) has been widely used to prepare diverse polymers.
Theoretical study of RNA-polymerase behavior considering the backtracking state
Authors: Kor Razieh , Mohammad-Rafiee Farshid
Published: July 2022

We develop a theoretical model to study the dynamical behavior of RNA polymerase in the transcription process in the presence of external stretching force considering the backtracking and arresting states.
A naringin-derived bioink enhances the shape fidelity of 3D bioprinting and efficiency of cartilage defect repair
Authors: Huang Yuting , Meng Xiaolin , Zhou Zheng , Zhu Wenxiang , Chen Xin , He Yahui , He Ning , Han Xiaoxiao , Zhou Dengming , Duan Xuanchu , Vadgama Pankaj M. , Liu Hairong
Published: July 2022

A NAR derived medical bioink for high shape fidelity 3D bioprinting and cartilage defect repair. MA: methacrylic anhydride, NARMA: methylacryloyl modified NAR, GEL: gelatin, GELMA: methylacryloyl modified GEL.
Automatic detection of long-duration transients in Fermi-GBM data
Authors: Kunzweiler F. , Biltzinger B. , Greiner J. , Burgess J. M.
Published: July 2022

Context. In the era of time-domain, multi-messenger astronomy, the detection of transient events on the high-energy electromagnetic sky has become more important than ever. Previous attempts to systematically search for onboard, untriggered events in the data of Fermi-GBM have been limited to short-duration signals with variability time scales smaller than ≈1 min. This is due to the dominance of background variations on longer timescales.

Aims. In this study, we aim to achieve a detection of slowly rising or long-duration transient events with high sensitivity and a full coverage of the GBM spectrum.

Methods. We made use of our earlier developed physical background model, which allows us to effectively decouple the signal from long-duration transient sources from the complex varying background seen with the Fermi-GBM instrument. We implemented a novel trigger algorithm to detect signals in the variations of the time series that is composed of simultaneous measures in the light curves of the different Fermi-GBM detectors in different energy bands. To allow for a continuous search in the data stream of the satellite, the new detection algorithm was embedded in a fully automatic data analysis pipeline. After the detection of a new transient source, we also performed a joint fit for spectrum and location using the BALROG algorithm.

Results. The results from extensive simulations demonstrate that the developed trigger algorithm is sensitive down to sub-Crab intensities (depending on the search timescale) and has a near-optimal detection performance. During a two month test run on real Fermi-GBM data, the pipeline detected more than 300 untriggered transient signals. We verified, for one of these transient detections, that it originated from a known astrophysical source, namely, the Vela X-1 pulsar, showing pulsed emission for more than seven hours. More generally, this method enables a systematic search for weak or long-duration transients.
Limit behaviour of random walks on ℤmwith two-sided membrane
Authors: Bogdanskii Victor , Pavlyukevich Ilya , Pilipenko Andrey
Published: July 2022

We study Markov chains on ℤm,m≥ 2, that behave like a standard symmetric random walk outside of the hyperplane (membrane)H= {0} × ℤm−1. The exit probabilities from the membrane (penetration probabilities) H are periodic and also depend on the incoming direction toH, what makes the membrane H two-sided. Moreover, sliding along the membrane is allowed. We show that the natural scaling limit of such Markov chains is a m-dimensional diffusion whose first coordinate is a skew Brownian motion and the otherm− 1 coordinates is a Brownian motion with a singular drift controlled by the local time of the first coordinate at 0. In the proof we utilize a martingale characterization of the Walsh Brownian motion and determine the effective permeability and slide direction. Eventually, a similar convergence theorem is established for the one-sided membrane without slides and random iid penetration probabilities.
The ornithophily of Impatiens sakeriana does not guarantee a preference by sunbirds
Authors: Mundi Onella , Awa Ii Taku , Chmel Kryštof , Ewome Francis Luma , Uceda-Gómez Guillermo , Janečková Petra , Janeček Štěpán
Published: July 2022

In recent decades, the tight mutual specialization between nectarivorous birds and ornithophilous plants has been questioned, and instead, high degrees of generalization and interaction asymmetry have been highlighted. Here, we studied interactions among two sunbirds and four plant species in two Mount Cameroon forests, with two plant species from each forest. First, we investigated whether sunbirds differ in frequencies of visitation to target plant species in natural conditions. Second, using a cage experiment, we investigated whether sunbirds prefer various plant species, plants with which they are more familiar and that occur in the habitat where they were caught and/or the only studied ornithophilous plant, Impatiens sakeriana. In natural conditions, the short-billed sunbird, Cinnyris reichenowi, fed more on flowers with shorter tubes than the long-billed sunbird, Cyanomitra oritis. Likewise, sunbirds differed in their experimental preferences. Local plants were generally preferred. This was most obvious in the case of I. sakeriana, which was often visited by both sunbirds, but only in the habitat where it grows naturally. This study supports the importance of associative learning. Together with other studies, we suggest that the signalling traits of flowers with bird pollination syndromes evolved to filter out other visitors rather than to attract bird pollinators.
Glocal intimacies: theorizing mobile media and intimate relationships
Authors: Cabañes Jason Vincent A , Uy-Tioco Cecilia S
Published: July 2022

This article develops the concept of “glocal intimacies,” capturing the role of mobile media in how people enact and reconfigure their increasingly global experiences of social relationships. It establishes the two foundational assumptions of this concept: the interplay of local and global cultures and the transformative role of mobile media. It then identifies the three key dimensions that characterize glocal intimacies: digital access, contextual localities, and sociotechnical dynamics. To provide empirical flesh to how these dimensions intersect, it comparatively discusses two ethnographic projects on privileged Filipinos and their mediated familial and romantic relationships.
Stool Interleukin-1β Differentiates Clostridioides difficile Infection (CDI) From Asymptomatic Carriage and Non-CDI Diarrhea
Authors: Villafuerte Gálvez Javier A , Pollock Nira R , Alonso Carolyn D , Chen Xinhua , Xu Hua , Wang Lamei , White Nicole , Banz Alice , Miller Mark , Daugherty Kaitlyn , Gonzalez-Luna Anne J , Barrett Caitlin , Sprague Rebecca , Garey Kevin W , Kelly Ciaran P
Published: July 2022

Background

Despite advances in the understanding and diagnosis of Clostridioides difficile infection (CDI), clinical distinction within the colonization–infection continuum remains an unmet need.

Methods

By measuring stool cytokines and antitoxin antibodies in well-characterized cohorts of CDI (diarrhea, nucleic acid amplification test [NAAT] positive), non-CDI diarrhea (NCD; diarrhea, NAAT negative), asymptomatic carriers (ASC; no diarrhea, NAAT positive) and hospital controls (CON; no diarrhea, NAAT negative), we aim to discover novel biological markers to distinguish between these cohorts. We also explore the relationship of these stool cytokines and antitoxin antibody with stool toxin concentrations and disease severity.

Results

Stool interleukin (IL) 1β, stool immunoglobulin A (IgA), and immunoglobulin G (IgG) anti–toxin A had higher (P < .0001) concentrations in CDI (n = 120) vs ASC (n = 43), whereas toxins A, B, and fecal calprotectin did not. Areas under the receiver operating characteristic curve (ROC-AUCs) for IL-1β, IgA, and IgG anti–toxin A were 0.88, 0.83, and 0.83, respectively. A multipredictor model including IL-1β and IgA anti–toxin A achieved an ROC-AUC of 0.93. Stool IL-1β concentrations were higher in CDI compared to NCD (n = 75) (P < .0001) and NCD + ASC+ CON (CON, n = 75) (P < .0001), with ROC-AUCs of 0.83 and 0.86, respectively. Stool IL-1β had positive correlations with toxins A (ρA = +0.55) and B (ρB = +0.49) in CDI (P < .0001) but not in ASC (P > .05).

Conclusions

Stool concentrations of the inflammasome pathway, proinflammatory cytokine IL-1β, can accurately differentiate CDI from asymptomatic carriage and NCD, making it a promising biomarker for CDI diagnosis. Significant positive correlations exist between stool toxins and stool IL-1β in CDI but not in asymptomatic carriers.
A Targeted Liquid Chromatography–Tandem Mass Spectrometry Method for Simultaneous Quantification of Peptides from the Carboxyl-terminal Region of Type III Procollagen, Biomarkers of Collagen Turnover
Authors: Huynh Huu Hien , Forrest Katrina , Becker Jessica O , Emrick Michelle A , Miller Geoffrey D , Moncrieffe Danielle , Cowan David A , Thomas Andreas , Thevis Mario , MacCoss Michael J , Hoffstrom Ben , Byers Peter H , Eichner Daniel , Hoofnagle Andrew N
Published: July 2022

Background

The development of analytical approaches to help reduce the risk of growth hormone (GH) doping is important to fair competition and the health of athletes. However, the reliable detection of GH use remains challenging. The identification of novel biomarkers of GH administration could lead to a better understanding of the physiological response to GH, more sensitive detection of the illicit use of GH in sport, and better management of patients treated for GH disorders.

Methods

We developed a targeted liquid chromatography–tandem mass spectrometry method to simultaneously quantify the carboxyl-terminal propeptide of type III procollagen (P-III-CP) and type III collagen degradation products in human serum. Following proteolysis, we instituted a simple acid precipitation step to reduce digested sample complexity before peptide immunoenrichment, which improved the recovery of one target peptide from serum. We evaluated the concentration of each biomarker at different age ranges and after GH administration in healthy participants.

Results

The assay was linear over an estimated concentration range of 0.3 to1.0 nM and 0.1 to 0.4 nM for each surrogate peptide of P-III-CP and collagen fragments, respectively. Intra-day and inter-day coefficients of variation were ≤15%. Biomarker concentrations appeared to vary with age and to reflect age-specific collagen turnover. Moreover, their concentrations changed after GH administration.

Conclusions

Our method quantifies the proteins belonging to the family of P-III-CP and type III collagen degradation products in human serum, which could be used to detect GH administration in athletes and better understand diseases involving GH therapy or altered type III collagen turnover.
Prometheus in Russia: from revolution to dissidence
Authors: But Ekaterina
Published: July 2022

This essay examines the development of the image of Prometheus as a symbol of the revolutionary in Russia and the Soviet Union. After providing a historical overview of pre-Soviet and early-Soviet receptions of Prometheus’ image in Alexander Scriabin’s symphony Prometheus: The Poem of Fire (Prometei: Poema Ognia, 1908–10) and in the unfinished production of the ancient Greek tragic trilogy at the Moscow Art Theatre (1925–27), I focus on the analysis of Prometheus’ myth in three screen adaptations: the 1936 film Prometheus (Prometei) by Soviet Ukrainian director Ivan Kavaleridze and the animated films The Return from Olympus (Vozvrashchenie s Olimpa, 1969), and Prometheus (Prometei, 1974) by Alexandra Snezhko-Blotskaya. I demonstrate that, besides the animation films directed by Snezhko-Blotskaya, the rest of the receptions were not successful at the time of their production. I examine how the creative programs of these projects did not fit the contemporary context, institutional framework, or official ideology because of technical, aesthetical, and political reasons. I argue that the screen receptions of Prometheus’ myth employed Prometheus’ image to reflect on and to address the changing political and cultural climate of the Soviet Union during critical periods of its history.
Alcohol consumption and subclinical and clinical coronary heart disease: a Mendelian randomization analysis
Authors: Hisamatsu Takashi , Miura Katsuyuki , Tabara Yasuharu , Sawayama Yuichi , Kadowaki Takashi , Kadota Aya , Torii Sayuki , Kondo Keiko , Yano Yuichiro , Fujiyoshi Akira , Yamamoto Takashi , Nakagawa Yoshihisa , Horie Minoru , Kimura Takeshi , Okamura Tomonori , Ueshima Hirotsugu ,   for the SESSA and ACCESS Research Groups
Published: July 2022

Aims

The potential effect of alcohol consumption on coronary heart disease (CHD) remains unclear. We used the variant rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) as an instrument to investigate the causal role of alcohol intake in subclinical and clinical CHD.

Methods

We conducted two Mendelian randomization studies: a cross-sectional study of coronary artery calcification (CAC) on computed tomography of 1029 healthy men (mean age, 63.8 years) and a case–control study of 421 men with CHD [acute coronary syndrome (ACS) or stable angina pectoris] who underwent coronary revascularization and 842 age-matched male controls.

Results

In the CAC study, medians (25%tiles, 75%tiles) of alcohol consumption by ALDH2-rs671 *2 homozygotes [n = 86 (8.4%)], *1*2 heterozygotes [n = 397 (38.5%)], and *1 homozygotes [n = 546 (53.1%)] were 0.0 (0.0, 0.0), 28.0 (0.0, 129.0), and 224.0 (84.0, 350.0) g/week, respectively. In age-adjusted Poisson regression with robust error variance, compared with *2 homozygotes, relative risks for prevalent CAC score >0, ≥100, and ≥300 in *1 homozygotes were 1.29 (95% confidence interval, 1.06–1.57), 1.76 (1.05–2.96), and 1.81 (0.80–4.09), respectively. In age-adjusted ordinal logistic regression for CAC distributions, we observed higher odds among *1 homozygotes [odds ratio, 2.19 (1.39–3.46)] and even among *1*2 heterozygotes [1.77 (1.11–2.82)] compared with *2 homozygotes. In the case–control study, conditional logistic regression revealed lower prevalence of *1 homozygotes among men with CHD [odds ratio, 0.54 (0.35–0.82)], especially ACS [0.46 (0.27–0.77)], than controls.

Conclusion

Our findings indicate a positive association of alcohol consumption with CAC burden but an inverse association with clinical CHD, especially ACS.
An entropy method for geodynamic modelling of phase transitions: capturing sharp and broad transitions in a multiphase assemblage
Authors: Dannberg Juliane , Gassmöller Rene , Li Ranpeng , Lithgow-Bertelloni Carolina , Stixrude Lars
Published: July 2022

Phase transitions play an important role for the style of mantle convection. While observations and theory agree that a substantial fraction of subducted slabs and rising plumes can move through the whole mantle at present day conditions, this behaviour may have been different throughout Earth’s history. Higher temperatures, such as in the early Earth, cause different phase transitions to be dominant, and also reduce mantle viscosity, favouring a more layered style of convection induced by phase transitions. A period of layered mantle convection in Earth’s past would have significant implications for the secular evolution of the mantle temperature and the mixing of mantle heterogeneities. The transition from layered to whole mantle convection could lead to a period of mantle avalanches associated with a dramatic increase in magmatic activity. Consequently, it is important to accurately model the influence of phase transitions on mantle convection. However, existing numerical methods generally preclude modelling phase transitions that are only present in a particular range of pressures, temperatures or compositions, and they impose an artificial lower limit on the thickness of phase transitions. To overcome these limitations, we have developed a new numerical method that solves the energy equation for entropy instead of temperature. This technique allows for robust coupling between thermodynamic and geodynamic models and makes it possible to model realistically sharp phase transitions with a wide range of properties and dynamic effects on mantle processes. We demonstrate the utility of our method by applying it in regional and global convection models, investigating the effect of individual phase transitions in the Earth’s mantle with regard to their potential for layering flow. We find that the thickness of the phase transition has a bigger influence on the style of convection than previously thought: with all other parameters being the same, a thin phase transition can induce fully layered convection where a broad phase transition would lead to whole-mantle convection. Our application of the method to convection in the early Earth illustrates that endothermic phase transitions may have induced layering for higher mantle temperatures in the Earth’s past.
Long-Term Outcomes After Ustekinumab Dose Intensification for Inflammatory Bowel Diseases
Authors: Dalal Rahul S , Pruce Jordan C , Allegretti Jessica R
Published: July 2022

Lay Summary

In this retrospective cohort study, we demonstrated that dose intensification of ustekinumab to every 4 or every 6 weeks was effective in both achieving and maintaining clinical remission for >40% of inflammatory bowel disease patients for up to 24 months.
Temporal Monitoring of the Floreana Island Galapagos Giant Tortoise Captive Breeding Program
Authors: Gray Rachel , Fusco Nicole , Miller Joshua M , Tapia Washington , Mariani Carol , Caccone Adalgisa , Jensen Evelyn L
Published: July 2022

Captive breeding programs benefit from genetic analyses that identify relatedness between individuals, assign parentage to offspring, and track levels of genetic diversity. Monitoring these parameters across breeding cycles is critical to the success of a captive breeding program as it allows conservation managers to iteratively evaluate and adjust program structure. However, in practice, genetic tracking of breeding outcomes is rarely conducted. Here, we examined the first three offspring cohorts (2017–2020) of the genetically informed captive breeding program for the Floreana Island Galapagos giant tortoise, Chelonoidis niger. This captive breeding program is unique as the Floreana tortoise has been extinct since the 1800s, but its genome persists, in part, in the form of living hybrids with the extant Volcano Wolf tortoise, C. becki. Breeding over the study period took place at the Galapagos National Park Directorate breeding facility in four corrals, each containing three females and two males. Using 17 microsatellite markers, we were able to assign parentage to 94 of the 98 offspring produced over the study period. We observe that despite the addition of more founders since the pilot breeding program, the effective population size remains low, and changes to the arrangements of breeding corrals may be necessary to encourage more equal reproductive output from the males. This study demonstrates the value of hybrids for species restoration and the importance of continually reassessing the outcomes of captive breeding.
Flexible exchange rates in emerging markets: shock absorbers or drivers of endogenous cycles?
Authors: Kohler Karsten , Stockhammer Engelbert
Published: July 2022

While flexible exchange rates are commonly regarded as shock absorbers, heterodox views suggest that they can play a pro-cyclical role in emerging markets. This article provides theoretical and empirical support for this view. Drawing on post-Keynesian and structuralist theories, we propose a simple model in which flexible exchange rates in conjunction with external shocks become endogenous drivers of boom-bust cycles, once financial effects from foreign-currency debt are accounted for. We present empirical evidence for regular cycles in nominal US-dollar exchange rates in several emerging markets that are closely aligned with cycles in economic activity. An econometric analysis suggests the presence of a cyclical interaction mechanism between exchange rates and output, in line with the theoretical model, in Chile, South Africa, and partly the Philippines. Further evidence indicates that such exchange rate cycles cannot exclusively be attributed to external factors, such as commodity prices, US monetary policy or the global financial cycle. We therefore argue that exchange rate cycles in emerging markets are driven by the interplay of external shocks and endogenous cycle mechanisms.
Correlation Between Postvaccination Anti-Spike Antibody Titers and Protection Against Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Population-Based Longitudinal Study
Authors: Vivaldi Giulia , Jolliffe David A , Faustini Sian , Shields Adrian M , Holt Hayley , Perdek Natalia , Talaei Mohammad , Tydeman Florence , Chambers Emma S , Cai Weigang , Li Wenhao , Gibbons Joseph M , Pade Corinna , McKnight Áine , Shaheen Seif O , Richter Alex G , Martineau Adrian R
Published: July 2022

In this population-based cohort of 7538 adults, combined immunoglobulin (Ig) G, IgA, and IgM (IgG/A/M) anti-spike titers measured after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination were predictive of protection against breakthrough SARS-CoV-2 infection. Discrimination was significantly improved by adjustment for factors influencing risk of SARS-CoV-2 exposure, including household overcrowding, public transport use, and visits to indoor public places. Anti-spike IgG/A/M titers showed positive correlation with neutralizing antibody titers (rs = 0.80 [95% confidence interval, .72–.86]; P < .001) and S peptide–stimulated interferon-γ concentrations (rs = 0.31 [.13–.47]; P < .001).
A Tunable, Simplified Model for Biological Latch Mediated Spring Actuated Systems
Authors: Cook Andrés , Pandhigunta Kaanthi , Acevedo Mason A , Walker Adam , Didcock Rosalie L , Castro Jackson T , O’Neill Declan , Acharya Raghav , Bhamla M Saad , Anderson Philip S L , Ilton Mark
Published: July 2022

Synopsis

We develop a model of latch-mediated spring actuated (LaMSA) systems relevant to comparative biomechanics and bioinspired design. The model contains five components: two motors (muscles), a spring, a latch, and a load mass. One motor loads the spring to store elastic energy and the second motor subsequently removes the latch, which releases the spring and causes movement of the load mass. We develop freely available software to accompany the model, which provides an extensible framework for simulating LaMSA systems. Output from the simulation includes information from the loading and release phases of motion, which can be used to calculate kinematic performance metrics that are important for biomechanical function. In parallel, we simulate a comparable, directly actuated system that uses the same motor and mass combinations as the LaMSA simulations. By rapidly iterating through biologically relevant input parameters to the model, simulated kinematic performance differences between LaMSA and directly actuated systems can be used to explore the evolutionary dynamics of biological LaMSA systems and uncover design principles for bioinspired LaMSA systems. As proof of principle of this concept, we compare a LaMSA simulation to a directly actuated simulation that includes either a Hill-type force-velocity trade-off or muscle activation dynamics, or both. For the biologically-relevant range of parameters explored, we find that the muscle force-velocity trade-off and muscle activation have similar effects on directly actuated performance. Including both of these dynamic muscle properties increases the accelerated mass range where a LaMSA system outperforms a directly actuated one.
City of Dreams
Authors: De la Roca Jorge , Ottaviano Gianmarco I P , Puga Diego
Published: July 2022

Bigger cities offer more valuable experiences and opportunities in exchange for higher housing costs. While higher-ability workers benefit more from bigger cities, they are not more likely to move to one. Our model of urban sorting by workers with heterogeneous self-confidence and ability suggests flawed self-assessment is partly to blame. Analysis of the National Longitudinal Survey of Youth 1979 data shows that, consistent with our model, young workers with high self-confidence are more likely to locate in a big city initially. For more experienced workers, ability plays a stronger role in determining location choices, but the lasting impact of earlier choices dampens their incentives to move.
An optimized survey strategy for the ERIS/NIX imager: searching for young giant exoplanets and very low mass brown dwarfs using the K-peak custom photometric filter
Authors: Dubber Sophie , Biller Beth , Bonavita Mariangela , Allers Katelyn , Fontanive Clémence , Kenworthy Matthew A , Bonnefoy Mickaël , Taylor William
Published: July 2022

We present optimal survey strategies for the upcoming NIX imager, part of the Enhanced Resolution Imager and Spectrograph instrument to be installed on the Very Large Telescope. We will use a custom 2.2 µm K-peak filter to optimize the efficiency of a future large-scale direct imaging survey, aiming to detect brown dwarfs and giant planets around nearby stars. We use the results of previous large-scale imaging surveys (primarily SPHERE SHINE and Gemini GPIES) to inform our choice of targets, as well as improved planet population distributions. We present four possible approaches to optimize survey target lists for the highest yield of detections: (i) targeting objects with anomalous proper motion trends, (ii) a follow-up survey of dense fields from SPHERE SHINE and Gemini GPIES, (iii) surveying nearby star-forming regions, and (iv) targeting newly discovered members of nearby young moving groups. We also compare the predicted performance of NIX to other state-of-the-art direct imaging instruments.
A measurement of the integrated Sachs–Wolfe effect with the Rapid ASKAP Continuum Survey
Authors: Bahr-Kalus Benedict , Parkinson David , Asorey Jacobo , Camera Stefano , Hale Catherine , Qin (秦斐) Fei
Published: July 2022

The evolution of the gravitational potentials on large scales due to the accelerated expansion of the Universe is an important and independent probe of dark energy, known as the integrated Sachs–Wolfe (ISW) effect. We measure this ISW effect through cross-correlating the cosmic microwave background maps from the Planck satellite with a radio continuum galaxy distribution map from the recent Rapid ASKAP Continuum Survey (RACS). We detect a positive cross-correlation at $\sim 2.8\, \sigma$ relative to the null hypothesis of no correlation. We parametrize the strength of the ISW effect through an amplitude parameter and find the constraints to be $A_{\mathrm{ISW}} = 0.94^{+0.42}_{-0.41}$, which is consistent with the prediction of an accelerating universe within the current concordance cosmological model, ΛCDM. The credible interval on this parameter is independent of the different bias models and redshift distributions that were considered when marginalizing over the nuisance parameters. We also detect a power excess in the galaxy autocorrelation angular power spectrum on large scales (ℓ ≤ 40), and investigate possible systematic causes.
Shapes of Milky-Way-mass galaxies with self-interacting dark matter
Authors: Vargya Drona , Sanderson Robyn , Sameie Omid , Boylan-Kolchin Michael , Hopkins Philip F , Wetzel Andrew , Graus Andrew
Published: July 2022

Self-interacting dark matter (SIDM) models offer one way to reconcile inconsistencies between observations and predictions from collisionless cold dark matter (CDM) models on dwarf-galaxy scales. In order to incorporate the effects of both baryonic and SIDM interactions, we study a suite of cosmological-baryonic simulations of Milky-Way (MW)-mass galaxies from the Feedback in Realistic Environments (FIRE-2) project where we vary the SIDM self-interaction cross-section σ/m. We compare the shape of the main dark matter (DM) halo at redshift z = 0 predicted by SIDM simulations (at σ/m = 0.1, 1, and 10 cm2 g−1) with CDM simulations using the same initial conditions. In the presence of baryonic feedback effects, we find that SIDM models do not produce the large differences in the inner structure of MW-mass galaxies predicted by SIDM-only models. However, we do find that the radius where the shape of the total mass distribution begins to differ from that of the stellar mass distribution is dependent on σ/m. This transition could potentially be used to set limits on the SIDM cross-section in the MW.
Predicting biosignatures for nutrient-limited biospheres
Authors: Nicholson A E , Daines S J , Mayne N J , Eager-Nash J K , Lenton T M , Kohary K
Published: July 2022

With the characterizations of potentially habitable planetary atmospheres on the horizon, the search for biosignatures is set to become a major area of research in the coming decades. To understand the atmospheric characteristics that might indicate alien life, we must understand the abiotic characteristics of a planet and how life interacts with its environment. In the field of biogeochemistry, sophisticated models of life-environment coupled systems demonstrate that many assumptions specific to Earth-based life, e.g. specific ATP maintenance costs, are unnecessary to accurately model a biosphere. We explore a simple model of a single-species microbial biosphere that produces CH4 as a byproduct of the microbes’ energy extraction – known as a type I biosignature. We demonstrate that although significantly changing the biological parameters has a large impact on the biosphere’s total population, such changes have only a minimal impact on the strength of the resulting biosignature, while the biosphere is limited by H2 availability. We extend the model to include more accurate microbial energy harvesting and show that adjusting microbe parameters can lead to a regime change where the biosphere becomes limited by energy availability and no longer fully exploits the available H2, impacting the strength of the resulting biosignature. We demonstrate that, for a nutrient-limited biosphere, identifying the limiting nutrient, understanding the abiotic processes that control its abundance, and determining the biospheres ability to exploit it, are more fundamental for making type I biosignature predictions than the details of the population dynamics of the biosphere.