bluuebunny/crossref_metadata_2025 huggingface dataset:
On Holomorphic Mappings with Compact Type Range
Authors: Jiménez-Vargas A. , Ruiz-Casternado D. , Sepulcre J. M.
Published: November 2022

Using Mujica’s linearization theorem, we extend to the holomorphic setting some classical characterizations of compact (weakly compact, Rosenthal, Asplund) linear operators between Banach spaces such as the Schauder, Gantmacher and Gantmacher–Nakamura theorems and the Davis–Figiel–Johnson–Pełczynski, Rosenthal and Asplund factorization theorems.
A semantic blocks model for human activity prediction in smart environments using time-windowed contextual data
Authors: Dunne Rob , Morris Tim , Harper Simon
Published: November 2022

Complex human activity prediction is a difficult problem for computer science. Simple behaviours can be mapped to sequence prediction algorithms with good results; however, real-world examples of activity are generally stochastic and much more computationally difficult to infer. One method for solving this problem is to utilise contextual data—clues surrounding the actual activity—to decipher what is about to happen next; in much the same way humans do. In this paper, we present the semantic blocks model (SBM), a method for using contextual data to infer the next activity in a smart home environment by augmenting the inference with contextual data, but also segmenting it into time-windowed sections of activity—or semantic blocks. Our proof-of-concept produces 74.55% accuracy on the CASAS smart home dataset, an increase on the comparable CRAFFT algorithm which produces 66.91% on the same dataset. We detail how our experimental prototype works using intersecting contextual data, and explore opportunities for further work by the research community.
Acquired Hemophilia in an Elderly Patient with Non-Small Cell Lung Cancer: a Case Report
Authors: Dulcetti Antonio , Bruscia C. , Malena D. M. , Benvenuto R. , Martocchia A. , Sentimentale A. , Tafaro L. , March M. Rocchietti , Martelletti P.
Published: November 2022

Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against coagulation factor VIII and characterized by spontaneous hemorrhage in patients with no previous family or personal history of bleeding. We report here a case of AHA that occurred in the Department of Medicina D’Urgenza in Sant’Andrea Hospital in a patient with previous diagnosis of NSLC. The aim of this article is to allow a more comprehensive knowledge of AHA that both for the rarity and the poor literature is underdiagnosed; for all these reasons, it is important that different specialists, like emergency specialists, experts in internal medicine, hematologists, and oncologists, acquire a more complete knowledge of the clinical and laboratory features of this disease, allowing an early diagnosis crucial for the evolution of the coagulopathy.
A time-periodic reaction-diffusion population model of a species subjected to harvesting on the boundary of a protected habitat
Authors: Searle K. D. , van Vuuren J. H.
Published: November 2022

The objective in this paper is to determine analytically a maximally sustainable pro-rata density-dependent harvest rate of a hypothetical biological species on the spatial boundary of a protected habitat (i.e. no harvesting of the species is allowed in the interior of the spatial domain). This is achieved by analysing an initial-boundary value model involving a reaction-diffusion equation in which the reaction term is a concave function of the population density, depends periodically on time, and varies spatially. The model is equipped with Robin boundary conditions modelling a continuum of potential pro-rata density-dependent harvest rates on the spatial boundary. A set of necessary and sufficient criteria for the existence of a unique positive periodic attractor of solutions to the model is established by employing the theory of comparison principles and monotone iteration schemes. Thereafter, a long-time asymptotic analysis of the population density is undertaken by invoking classical results from the theory of eigenproblems. In this way, the aforementioned necessary and sufficient conditions are rendered more practical in terms of an upper bound on the maximal allowable pro-rata density-dependent harvest rate. Moreover, important properties of the time-periodic attractor of solutions are established to guarantee the existence of a density pro-rata harvest rate which maximises the total harvest per unit time at equilibrium.
The variationally principle of two-temperature thermoelasticity in the absence of the energy dissipation theorem
Authors: Al-Lehaibi Eman A. N.
Published: November 2022

Youssef introduced two-temperature thermoelasticity without energy dissipation theorem. This theorem depends upon two distinct temperatures: the conductive temperature and the thermo-dynamical temperature. Through this work, the variational principle theorem will be obtained for an isotropic, homogeneous, and thermoelastic body in the context of two-temperature thermoelasticity without energy dissipation theorem.
Impact of the place on human health during pandemic and methods to enhance
Authors: Mowafy Mohamed Abdelbary Wafa
Published: November 2022

The spread of COVID-19 worldwide pushed many governments to impose curfews on citizens, that lead a major number of people to stay longer times at certain places in their homes. This is descriptive research, as this paper demonstrates the possibility of impact of the place on its occupant’s health, also it reviews the literature to present a framework to deal with that case in the future, whether there is a need for a new building or for just some modifications in existing ones. The research results showed that there is a certain impact of the place on the human physical and mental health, which results from one or both, the natural earth electromagnetic field and the shape design and proportions. In conclusion there are many methods and theories to deal with the energies of the place that have a negative impact on humans, one of them is to apply a regulatory energy that eliminates the negative impact of the existing energies, whether natural or artificial.
Secret Writing in the Long Eighteenth Century
Authors: Ellison Katherine
Published: November 2022

Cryptology of the long eighteenth century became an explicit discipline of secrecy. Theorized in pedagogical texts that reached wide audiences, multimodal methods of secret writing during the period in England promoted algorithmic literacy, introducing reading practices like discernment, separation, recombination, and pattern recognition. In composition, secret writing manipulated materials and inspired new technologies in instrumentation, computation, word processing, and storage. Cryptology also revealed the visual habits of print and the observational consequences of increasing standardization in writing, challenging the relationship between print and script. Secret writing served not only military strategists and politicians; it gained popularity with everyday readers as a pleasurable cognitive activity for personal improvement and as an alternative way of thinking about secrecy and literacy.
Reversing the Arrow of Time
Authors: Roberts Bryan W.
Published: November 2022

The arrow of time refers to the curious asymmetry that distinguishes the future from the past. Reversing the Arrow of Time argues that there is an intimate link between the symmetries of 'time itself' and time reversal symmetry in physical theories, which has wide-ranging implications for both physics and its philosophy. This link helps to clarify how we can learn about the symmetries of our world; how to understand the relationship between symmetries and what is real, and how to overcome pervasive illusions about the direction of time. Roberts explains the significance of time reversal in a way that intertwines physics and philosophy, to establish what the arrow of time means and how we can come to know it. This book is both mathematically and philosophically rigorous yet remains accessible to advanced undergraduates in physics and philosophy of physics. This title is also available as Open Access on Cambridge Core.
Agnès Sorel and the French Monarchy
Authors: Adams Tracy
Published: November 2022

Agnès Sorel (1428-1450), beautiful favourite of Charles VII of France and first in the long genealogy of French royal mistresses, was mysteriously poisoned in the prime of life. Agnès, part of a network of royal 'favourites', is equally interesting for her political activity. And yet, no scholarly study in English of her exists. This study brings her story to an English-speaking audience, examining her in her historical context, that is, the factional struggle for power waged against Charles VII by the dauphin Louis and the king’s final routing of the English. It then traces Agnès’s afterlife, exploring her roles as founding mother of the tradition of the French royal mistress and foil for the less popular holders of the 'office'; as erotic fantasy figure for nineteenth-century historians 're-inventing' the Middle Ages; and, most recently, as poignant victim for fans of the true crime genre.
At the Frontiers of State Responsibility
Authors: Pijnenburg Annick
Published: November 2022

States cooperate to stem irregular migration flows, yet migration control agreements often result in widespread violations of the socio-economic rights of people on the move contained in the Global South. This book examines the States that are responsible for these violations.
Netherlandish and Italian Female Portraiture in the Fifteenth Century
Authors: Toreno Elisabetta
Published: November 2022

This book investigates the aesthetic and conceptual characteristics of fifteenth-century female portraiture on panel. Portraits of women increased substantially during this century. They formed part of a material and a visual culture borne out of the rapid rise of an oligarchy from entrepreneurial activities that was especially advanced in the urbanised territories of Italy and Flanders. For this reason, the portraits in this book are by Netherlandish and Italian painters. They are simultaneously illustrative of the emancipation of the genre from its medieval idiom, and of the responses to the matrix of patriarchy, under which society was organised.

Patriarchy is an androcentric structure that places women in a paradoxical situation of legal and social disenfranchisement on the account of purported psychophysical inadequacy, whilst making them the catalysts, through arranged marriages, for the success of the spheres of power, which are controlled by men. Thus, these portraits are also a window into women's lives in this structure. This book is the first systematic study of their sign-system and of the feminine experience of seeing and being seen, at the intersection of disciplines that include art history, anthropology, legal history, philosophy. The surprising results suggest new interpretations of form and function in female portraiture, women's active role in the imaging process and the early instances of a pro-women ideology.
Childhood maltreatment and leukocyte telomere length in men and women with chronic illness: an evaluation of moderating and mediating influences
Authors: Connor Alexandra , Starnino Louisia , Busque Lambert , Tardif Jean-Claude , Bourgoin Vincent , Dubé Marie-Pierre , Busseuil David , D'Antono Bianca
Published: November 2022

Background

Childhood maltreatment can result in lifelong psychological and physical sequelae, including coronary artery disease (CAD). Mechanisms leading to increased risk of illness may involve emotional dysregulation and shortened leukocyte telomere length (LTL).

Methods

To evaluate whether (1) childhood maltreatment is associated with shorter LTL among older adults with CAD or other chronic illnesses; (2) sex and/or CAD status influence these results; and (3) symptoms of anxiety, depression, and stress moderate or mediate the association between childhood maltreatment and LTL, men and women (N = 1247; aged 65 ± 7.2 years) with and without CAD completed validated questionnaires on childhood maltreatment, symptoms of depression, anxiety, and perceived stress. LTL was measured using quantitative polymerase chain reaction. Analyses included bivariate correlations, hierarchical regressions, and moderation/mediation analyses, controlling for sociodemographic and lifestyle variables.

Results

Childhood maltreatment was associated with significantly shorter LTL (r = −0.059, p = 0.038, b = −0.016, p = 0.005). This relation was not moderated by depression, anxiety, nor perceived stress, though there was mitigated evidence for absence of a maltreatment-LTL relation in men with CAD. Stress perception (but not anxiety or depression) partially mediated the relation between childhood maltreatment and LTL [Indirect effect, b = −0.0041, s.e. = 0.002, 95% CI (−0.0085 to −0.0002)].

Conclusions

Childhood maltreatment was associated with accelerated biological aging independently of patient characteristics. Emotional dysregulation resulting in chronic stress may contribute to this process. Whether stress management or other interventions may help prevent or slow premature aging in those who have suffered maltreatment requires study.
Mobile Health in China: Well Integrated or a New Divide?
Authors: Sun Lujia , Buijsen Martin
Published: November 2022

The application of mobile health holds promises of achieving greater accessibility in the evolving health care sector. The active engagement of private actors drives its growth, while the challenges that exist between health care privatization and equitable access are a concern. This article selects the private internet hospital in China as a case study. It indicates that a market-oriented regulatory mechanism of private mobile health will contribute little to improving health equity from the perspectives of egalitarians and libertarians. By integrating the capability approach and the right to health, it is claimed that mobile health is a means of accessing health care for everyone, where substantive accessibility should be emphasized. With this view, this article provides policy recommendations that reinforce private sector engagement for mobile health, recognizing liberty, equity, and collective responsibility in the Chinese context.
Gender stereotypes in print and online media coverage of Slovak presidential candidates in 2009 and 2019
Authors: Žuffová Mária
Published: November 2022

In Slovakia, women are poorly represented in politics and public life. Yet it is the first country in Central Europe with a female president. By applying a mixed-methods approach to analyzing an original dataset containing media coverage of leading presidential candidates (n = 1492), this study explores how the media covered them and discusses under what conditions gender-stereotypical coverage could be detrimental or beneficial to electoral outcomes. The results show media outlet type was not significantly associated with a gender-stereotypical attribution of communal and agentic traits to candidates. Tabloids and quality press equally perpetuated gender stereotypes. Irrespective of their gender, journalists were more likely to depict women candidates as possessing communal qualities perceived as incompatible with leadership. However, findings from the qualitative analysis suggest that when corruption perception is high, and public trust in institutions is low, communal traits stereotypically attributed to women are appreciated. Novelty also works to women’s advantage. These findings have important implications for women candidates’ campaign strategies.
Detectable Increase in Global Land Areas Susceptible to Precipitation Reversals Under the RCP8.5 Scenario
Authors: Cheng Linyin , Liu Zhiyong
Published: November 2022

Of rising concern is the consecutive occurrence of contrasting precipitation extremes such as droughts followed by severe floods, which tips a precarious balance with lasting impacts on human and natural systems. However, it is not clear how the risk of such precipitation reversals may change over time at the global scale. Using precipitation data from the Community Earth System Model Version 1 (CESM1) Large Ensemble Simulations (LENS), we examined changes in the likelihood and spatial distribution of low‐intensity dry‐to‐wet fluctuations and more severe shifts from meteorological droughts to pluvials over global land areas via a conditional statistical framework. Our analysis of CESM1‐LENS leads to the conclusion that the worst‐case climate change scenario, that is, RCP8.5 can increase the percent of global land areas susceptible to both low‐intensity and more severe precipitation reversals by the end of the twenty‐first century, while inducing disproportionate impacts at regional scales depending on the severity of precipitation reversals. Particularly, we find 13.6% of global land areas may be depressed by interannual dry‐to‐wet events with a transition probability of greater than 0.5 in the twenty‐first century, quintupling the figure in the past century. The increase in the susceptible global land areas further indicates that new local hotspots with low‐frequency drought‐pluvial seesaws are more likely to emerge under the effects of enhancing anthropogenic greenhouse gases. Collectively, the study is expected to provide useful information for policy makers and infrastructure operators to prioritize actions that affect water resource objectives of flood control, drought mitigation, and water quality protection.
Large Ensemble Simulation for Investigating Predictability of Precursor Vortices of Typhoon Faxai in 2019 With a 14‐km Mesh Global Nonhydrostatic Atmospheric Model
Authors: Yamada Yohei , Miyakawa Tomoki , Nakano Masuo , Kodama Chihiro , Wada Akiyoshi , Nasuno Tomoe , Chen Ying‐Wen , Yamazaki Akira , Yashiro Hisashi , Satoh Masaki
Published: November 2022

Typhoon Faxai hit Japan in 2019 and severely damaged the Tokyo metropolitan area. To mitigate such damages, a good track forecast is necessary even before the typhoon formation. To investigate the predictability of the genesis and movement of a precursor vortex and its relationship with the synoptic‐scale flow, 100‐member ensemble simulations of Typhoon Faxai were performed using a 14‐km mesh global nonhydrostatic atmospheric model, which started from 16 different initial days (i.e., 1,600 members in total). The results show that the model could predict an enhanced risk of a Faxai‐like vortex heading toward Japan 2 weeks before landfall, which was up to 70%. The reason for the enhancement was a rapid increase in the members reproducing a precursor vortex from 15 to 12 days before landfall in Japan. In addition, the upper‐tropospheric vortex played an essential role in the track simulation of Faxai.
Simulated Cycles of East Asian Temperature and Precipitation Over the Past 425 ka
Authors: Dai Gaowen , Zhang Zhongshi , Otterå Odd Helge , Langebroek Petra , Yan Qing , Zhang Ran
Published: November 2022

Records from a wide range of geological archives covering the last few glacial‐interglacial cycles show large inconsistencies in the East Asian summer monsoon variability, which severely hampers our understanding of the evolution and potential mechanisms of the regional East Asian climate on orbital timescales. Here, we examine the simulated temperature and precipitation in East Asia based on a series of equilibrium simulations conducted for the past 425 ka, and we investigate the sensitivity of temperature and precipitation to potential forcings. Our simulations show that, in East Asia, the seasonal mean temperature is dominated by a ∼20‐kyr cycle, and the annual mean temperature (AMT) is dominated by a ∼100‐kyr cycle, which is consistent with previous modeling efforts and geological reconstructions. Additional sensitivity experiments indicate that the greenhouse gas concentration, in combination with the ice volume, is the dominant force for the variations of AMT in East Asia on orbital timescales. For the precipitation in East Asia, our equilibrium simulations and additional sensitivity experiments, together with comprehensive model‐data intercomparison analysis, suggest that the cycles of simulated annual mean precipitation over East Asia are highly model‐dependent, although the dominant ∼20‐kyr cycle in summer precipitation appears to be a robust feature. Overall, the results highlight the large model uncertainty with regard to the relative roles of forcings in hydroclimate variations in East Asia on orbital time scales. There is, therefore, an urgent need to implement more realistic precipitation schemes in models in order to decrease the model spread in simulated precipitation.
Lithology, Pore‐Filling Media, and Pore Closure Depth Beneath InSight on Mars Inferred From Shear Wave Velocities
Authors: Kilburn Richard , Dasent Jhardel , Wright Vashan , Manga Michael
Published: November 2022

We quantify the volume and distribution of water, cement, sediments, and fractured rocks within the Martian crust beneath NASA's InSight (Interior Exploration using Seismic Investigations, Geodesy, and Heat Transport mission) lander by using rock physics models to interpret shear wave velocities (Vs) measured from InSight data. The models assume that Mars' crust comprises sediments and fractured rocks whose pores and fractures host variable combinations of gas, liquid water, and mineral cements. Measured Vs in the upper crust (0–8 km) can be explained by layers of minimally (<2%) cemented sediments and gas‐filled fractured basalts. Measured Vs in the deeper crust (8–20 km) can be explained by fractured basalts or more felsic igneous rocks (modeled here as 100% plagioclase feldspar) that is unfractured or has up to 23% porosity. Open pores in the deeper crust could host gas, liquid water, and up to 2% cement. Modeled Vs are too low for a seismically detectable ice‐saturated cryosphere in the upper crust and temperatures are too high to freeze liquid water in the deeper crust. Notably, with Vs alone, we are unable to distinguish between liquid water and gas within the pores.
An Optimized Solution to Long‐Distance Flight Routes Under Extreme Cosmic Radiation
Authors: Xue Dabin , Yang Jian , Liu Zhizhao , Wang Bing
Published: November 2022

During extraordinary space weather, cosmic radiation can be significant enough to pose a threat to aircrew health. Traditional methods of reducing massive cosmic radiation exposure include flight cancellation, lowering flying altitudes, and flight rerouting. However, flight cancellation can result in additional financial expenditures, while lowering flight altitudes and rerouting can consequently cause more fuel consumption or even violation of airspace rights. As a result, we use a multi‐objective optimization model to assign optimal flight altitude and speed to reduce the overall weighted sum of cosmic radiation and fuel consumption. The simulation scenario is based on a space weather event with dramatically increased cosmic radiation that occurs during a routine international flight from Tokyo to London. Our results show that the proposed model can reduce fuel consumption while satisfying cosmic radiation limits recommended by the Council of the European Union if the forecasts of cosmic radiation are sufficiently accurate. In addition, a Pareto frontier is provided as a tactical air traffic management guideline. Our study provides insight into future policymaking for air transportation during harsh space weather conditions.
A Framework to Calibrate Ecosystem Demography Models Within Earth System Models Using Parallel Surrogate Global Optimization
Authors: Cheng Yanyan , Xia Wei , Detto Matteo , Shoemaker Christine A.
Published: November 2022

The climatic feedbacks from vegetation, particularly from tropical forests, can alter climate through land‐atmospheric interactions. Expected shifts in species composition can alter these interactions with profound effects on climate and terrestrial ecosystem dynamics. Ecosystem demographic (ED) models can explicitly represent vegetation dynamics and are a key component of next‐generation Earth System Models (ESMs). Although ED models exhibit greater fidelity and allow more direct comparisons with observations, their interacting parameters can be more difficult to calibrate due to the complex interactions among vegetation groups and physical processes. In addition, while representation of forest successional coexistence in ESMs is necessary to accurately capture forest‐climate interactions, few models can simulate forest coexistence and few studies have calibrated coexisted forest species. Furthermore, although both vegetation characteristics and soil properties affect vegetation dynamics, few studies have paid attention to jointly calibrating parameters related to these two processes. In this study, we develop a computationally‐efficient and physical model structure‐based framework that uses a parallel surrogate global optimization algorithm to calibrate ED models. We calibrate two typically coexisted tropical tree species, early and late successional plants, in a state‐of‐the‐art ED model that is capable of simulating successional diversity in forests. We concurrently calibrate vegetation and soil parameters and validate results against carbon, energy, and water cycle measurements collected in Barro Colorado Island, Panama. The framework can find optimal solutions within 4–12 iterations for 19‐dimensional problems. The calibration for tropical forests has important implications for predicting land‐atmospheric interactions and responses of tropical forests to environmental changes.
An fMRI Dataset for Concept Representation with Semantic Feature Annotations
Authors: Wang Shaonan , Zhang Yunhao , Zhang Xiaohan , Sun Jingyuan , Lin Nan , Zhang Jiajun , Zong Chengqing
Published: November 2022

The neural representation of concepts is a focus of many cognitive neuroscience studies. Prior works studying concept representation with neural imaging data have been largely limited to concrete concepts. The use of relatively small and constrained sets of stimuli leaves open the question of whether the findings can generalize other concepts. We share an fMRI dataset in which 11 participants thought of 672 individual concepts, including both concrete and abstract concepts. The concepts were probed using words paired with images in which the words were selected to cover a wide range of semantic categories. Furthermore, according to the componential theories of concept representation, we collected the 54 semantic features of the 672 concepts comprising sensory, motor, spatial, temporal, affective, social, and cognitive experiences by crowdsourcing annotations. The quality assessment results verify this as a high-quality neuroimaging dataset. Such a dataset is well suited to study how the brain represents different semantic features and concepts, creating the essential condition to investigate the neural representation of individual concepts.
Initial evaluation of extracorporeal immunomodulatory therapy for the treatment of critically ill COVID-19 infected patients
Authors: Lemoine Sandrine , Penny Jarrin , Fraser Douglas D. , Salerno Fabio R. , Dorie Justin , Tamasi Tanya , Arntfield Robert , House Andrew , Slessarev Marat , McIntyre Christopher W.
Published: November 2022

Severe COVID-19 infection results in significant immune dysregulation resulting from excessive recruitment and activation of neutrophils. The aim of this study was to confirm feasibility, initial safety and detect signal of efficacy of a non-propriety device delivered using an intermittent extra-corporeal system (LMOD) allowing leucocytes modulation in the setting of Severe COVID-19 infection. Twelve patients were recruited. Inclusion criteria were > 18 years age, confirmed COVID-19, acute respiratory distress syndrome requiring mechanical support and hypotension requiring vasopressor support. Primary end point was vasopressor requirements (expressed as epinephrine dose equivalents) and principle secondary endpoints related to safety, ability to deliver the therapy and markers of inflammation assessed over five days after treatment initiation. LMOD treatment appeared safe, defined by hemodynamic stability and no evidence of white cell number depletion from blood. We demonstrated a significant decrease in vasopressor doses (−37%, p = 0.02) in patients receiving LMOD therapy (despite these patients having to tolerate an additional extracorporeal intermittent therapy). Vasopressor requirements unchanged/increasing in control group (+ 10%, p = 0.48). Although much about the use of this therapy in the setting of severe COVID-19 infection remains to be defined (e.g. optimal dose and duration), this preliminary study supports the further evaluation of this novel extracorporeal approach.
Gut microbiota analysis for prediction of clinical relapse in Crohn’s disease
Authors: Buffet-Bataillon Sylvie , Bouguen Guillaume , Fleury François , Cattoir Vincent , Le Cunff Yann
Published: November 2022

The role of intestinal bacterial microbiota has been described as key in the pathophysiology of Crohn’s disease (CD). CD is characterized by frequent relapses after periods of remission which are not entirely understood. In this paper, we investigate whether the heterogeneity in microbiota profiles in CD patients could be a suitable predictor for these relapses. This prospective observational study involved 259 CD patients, in which 41 provided an additional total of 62 consecutive fecal samples, with an average interval of 25 weeks in between each of these samples. Fecal microbiota was analyzed by massive genomic sequencing through 16 S rRNA amplicon sampling. We found that our 259 CD patients could be split into three distinct subgroups of microbiota (G1, G2, G3). From G1 to G3, we noticed a progressive decrease in alpha diversity (p ≤ 0.0001) but no change in the fecal calprotectin (FC) level. Focusing on the 103 consecutive samples from 41 CD patients, we showed that the patients microbiota profiles were remarkably stable over time and associated with increasing symptom severity. Investigating further this microbiota/severity association revealed that the first signs of aggravation are (1) a loss of the main anti-inflammatory Short-Chain Fatty Acids (SCFAs) Roseburia, Eubacterium, Subdoligranumum, Ruminococcus (P < 0.05), (2) an increase in pro-inflammatory pathogens Proteus, Finegoldia (P < 0.05) while (3) an increase of other minor SCFA producers such as Ezakiella, Anaerococcus, Megasphaera, Anaeroglobus, Fenollaria (P < 0.05). Further aggravation of clinical signs is significantly linked to the subsequent loss of these minor SCFAs species and to an increase in other proinflammatory Proteobacteria such as Klebsiella, Pseudomonas, Salmonella, Acinetobacter, Hafnia and proinflammatory Firmicutes such as Staphylococcus, Enterococcus, Streptococcus. (P < 0.05). To our knowledge, this is the first study (1) specifically identifying subgroups of microbiota profiles in CD patients, (2) relating these groups to the evolution of symptoms over time and (3) showing a two-step process in CD symptoms’ worsening. This paves the way towards a better understanding of patient-to-patient heterogeneity, as well as providing early warning signals of future aggravation of the symptoms and eventually adapting empirically treatments.
Lassa antiviral LHF-535 protects guinea pigs from lethal challenge
Authors: Cashman Kathleen A. , Wilkinson Eric R. , Posakony Jeffrey , Madu Ikenna G. , Tarcha Eric J. , Lustig Kurt H. , Korth Marcus J. , Bedard Kristin M. , Amberg Sean M.
Published: November 2022

LHF-535 is a small molecule antiviral currently in development for the treatment of Lassa fever, a zoonotic disease endemic in West Africa that generates significant morbidity and mortality. Current treatment options are inadequate, and there are no approved therapeutics or vaccines for Lassa fever. LHF-535 was evaluated in a lethal guinea pig model of Lassa pathogenesis, using once-daily administration of a fixed dose (50 mg/kg/day) initiating either 1 or 3 days after inoculation with a lethal dose of Lassa virus. LHF-535 reduced viremia and clinical signs and protected all animals from lethality. A subset of surviving animals was rechallenged four months later with a second lethal challenge of Lassa virus and were found to be protected from disease. LHF-535 pharmacokinetics at the protective dose in guinea pigs showed plasma concentrations well within the range observed in clinical trials in healthy volunteers, supporting the continued development of LHF-535 as a Lassa therapeutic.
Network location and clustering of genetic mutations determine chronicity in a stylized model of genetic diseases
Authors: Nyczka Piotr , Falk Johannes , Hütt Marc-Thorsten
Published: November 2022

In a highly simplified view, a disease can be seen as the phenotype emerging from the interplay of genetic predisposition and fluctuating environmental stimuli. We formalize this situation in a minimal model, where a network (representing cellular regulation) serves as an interface between an input layer (representing environment) and an output layer (representing functional phenotype). Genetic predisposition for a disease is represented as a loss of function of some network nodes. Reduced, but non-zero, output indicates disease. The simplicity of this genetic disease model and its deep relationship to percolation theory allows us to understand the interplay between disease, network topology and the location and clusters of affected network nodes. We find that our model generates two different characteristics of diseases, which can be interpreted as chronic and acute diseases. In its stylized form, our model provides a new view on the relationship between genetic mutations and the type and severity of a disease.
A mass spectrometry-based approach for the identification of Kpnβ1 binding partners in cancer cells
Authors: Okpara Michael O. , Hermann Clemens , van der Watt Pauline J. , Garnett Shaun , Blackburn Jonathan M. , Leaner Virna D.
Published: November 2022

Karyopherin beta 1 (Kpnβ1) is the principal nuclear importer of cargo proteins and plays a role in many cellular processes. Its expression is upregulated in cancer and essential for cancer cell viability, thus the identification of its binding partners might help in the discovery of anti-cancer therapeutic targets and cancer biomarkers. Herein, we applied immunoprecipitation coupled to mass spectrometry (IP-MS) to identify Kpnβ1 binding partners in normal and cancer cells. IP-MS identified 100 potential Kpnβ1 binding partners in non-cancer hTERT-RPE1, 179 in HeLa cervical cancer, 147 in WHCO5 oesophageal cancer and 176 in KYSE30 oesophageal cancer cells, including expected and novel interaction partners. 38 binding proteins were identified in all cell lines, with the majority involved in RNA metabolism. 18 binding proteins were unique to the cancer cells, with many involved in protein translation. Western blot analysis validated the interaction of known and novel binding partners with Kpnβ1 and revealed enriched interactions between Kpnβ1 and select proteins in cancer cells, including proteins involved in cancer development, such as Kpnα2, Ran, CRM1, CCAR1 and FUBP1. Together, this study shows that Kpnβ1 interacts with numerous proteins, and its enhanced interaction with certain proteins in cancer cells likely contributes to the cancer state.
Mechanical performance under dynamic loading of rubberized asphalt mixtures with highly-porous vesicular aggregate
Authors: Franesqui Miguel A. , Yepes Jorge , Gallego Juan
Published: November 2022

In volcanic regions, the use of certain abundant aggregates of scoriaceous nature with high porosity to manufacture bituminous paving mixtures is a major problem due to the excessive heterogeneity, absorption and limited strength of these aggregates. Consequently, the properties of the mixtures often do not meet technical specifications. The aim of this research is to study the improvement of the mechanical performance of asphalt mixtures with these residual volcanic aggregates by using binders modified with rubber from end-of-life tyres, since environmental and economic requirements make it necessary to reuse both types of waste. Laboratory studies determining the compactability, dynamic stiffness, fatigue resistance and elastic constants have made it possible to characterise the mechanical performance of these mixtures during production and in service, and to compare them with conventional mixtures. It was found that the use of tyre rubber modified bitumen makes compaction somewhat more difficult, but reduces the particle size degradation of the porous aggregates and improves the mixture performance and durability, showing higher stiffness moduli and increased resistance to fatigue.
Acute gut inflammation reduces neural activity and spine maturity in hippocampus but not basolateral amygdala
Authors: Matisz Chelsea E. , Semenoff Nadia , Ahmed Al-Shaimaa F. , Griffin Lateece , Wallace Laurie E. , McNabb Parker , Gibb Robbin , Sharkey Keith A. , Gruber Aaron J.
Published: November 2022

Gastrointestinal tract (gut) inflammation increases stress and threat-coping behaviors, which are associated with altered activity in fear-related neural circuits, such as the basolateral amygdala and hippocampus. It remains to be determined whether inflammation from the gut affects neural activity by altering dendritic spines. We hypothesized that acute inflammation alters dendritic spines in a brain region-specific manner. Here we show that acute gut inflammation (colitis) evoked by dextran sodium sulfate (DSS) did not affect the overall spine density in the CA1 region of hippocampus, but increased the relative proportion of immature spines to mature spines on basal dendrites of pyramidal neurons. In contrast, in animals with colitis, no changes in spine density or composition on dendrites of pyramidal cells was observed in the basolateral amygdala. Rather, we observed decreased spine density on dendrites of stellate neurons, but not the relative proportions of mature vs immature spines. We used cFos expression evoked by the forced swim task as a measure of neural activity during stress and found no effect of DSS on the density of cFos immunoreactive neurons in basolateral amygdala. In contrast, fewer CA1 neurons expressed cFos in mice with colitis, relative to controls. Furthermore, CA1 cFos expression negatively correlated with active stress-coping in the swim task and was negatively correlated with gut inflammation. These data reveal that the effects of acute gut inflammation on synaptic remodeling depend on brain region, neuronal phenotype, and dendrite location. In the hippocampus, a shift to immature spines and hypoactivity are more strongly related to colitis-evoked behavioral changes than is remodeling in basolateral amygdala.
Complementary anti-cancer pathways triggered by inhibition of sideroflexin 4 in ovarian cancer
Authors: Tesfay Lia , Paul Bibbin T. , Hegde Poornima , Brewer Molly , Habbani Samrin , Jellison Evan , Moore Timothy , Wu Hao , Torti Suzy V. , Torti Frank M.
Published: November 2022

DNA damaging agents are a mainstay of standard chemotherapy for ovarian cancer. Unfortunately, resistance to such DNA damaging agents frequently develops, often due to increased activity of DNA repair pathways. Sideroflexin 4 (SFXN4) is a little-studied inner mitochondrial membrane protein. Here we demonstrate that SFXN4 plays a role in synthesis of iron sulfur clusters (Fe-S) in ovarian cancer cells and ovarian cancer tumor-initiating cells, and that knockdown of SFXN4 inhibits Fe-S biogenesis in ovarian cancer cells. We demonstrate that this has two important consequences that may be useful in anti-cancer therapy. First, inhibition of Fe-S biogenesis triggers the accumulation of excess iron, leading to oxidative stress. Second, because enzymes critical to multiple DNA repair pathways require Fe-S clusters for their function, DNA repair enzymes and DNA repair itself are inhibited by reduction of SFXN4. Through this dual mechanism, SFXN4 inhibition heightens ovarian cancer cell sensitivity to DNA-damaging drugs and DNA repair inhibitors used in ovarian cancer therapy, such as cisplatin and PARP inhibitors. Sensitization is achieved even in drug resistant ovarian cancer cells. Further, knockout of SFXN4 decreases DNA repair and profoundly inhibits tumor growth in a mouse model of ovarian cancer metastasis. Collectively, these results suggest that SFXN4 may represent a new target in ovarian cancer therapy.
Validation of seismic hazard curves using a calibrated 14 ka lacustrine record in the Eastern Alps, Austria
Authors: Daxer Christoph , Huang Jyh-Jaan Steven , Weginger Stefan , Hilbe Michael , Strasser Michael , Moernaut Jasper
Published: November 2022

Seismic hazard maps are crucial for earthquake mitigation and mostly rely on probabilistic seismic hazard analysis (PSHA). However, the practise and value of PSHA are under debate because objective testing procedures for seismic hazard maps are scarce. We present a lacustrine turbidite record revealing 44 earthquakes over the last ~ 14 ka and use it to test seismic hazard curves in southern Austria. We derive local seismic intensities for paleo-earthquakes by applying scaling relationships between the sedimentary imprint and seismic intensity of well-documented historical earthquakes. The last ~ 2.8 ka of the record agree with a Poissonian recurrence behaviour and therefore a constant hazard rate, which is the modelling choice for standard PSHA. The lacustrine data are consistent with the intensity-frequency relationship of the local seismic hazard curve, confirming the current PSHA approach for this part of Austria. On longer timescales, distinct phases of enhanced regional seismicity occurred, indicating a potential increase of seismic hazard after large earthquakes—a factor hitherto disregarded in the PSHA of the Eastern Alps. Our new method forms an independent procedure to test hazard maps in any setting where suitable lake systems are available.
The relationship between occupational stress and job burnout among female manufacturing workers in Guangdong, China: a cross-sectional study
Authors: Zhou Shanyu , Chen Huiqing , Liu Ming , Wang Tianjian , Xu Haijuan , Li Rongzong , Su Shibiao
Published: November 2022

This study aims to investigate the relationship between occupational stress and job burnout in female manufacturing workers. A random sample of 1081 female workers in electronic manufacturing in Guangdong Province participated in the present study. An anonymous self-administered questionnaire that covered social-demographic characteristics, the Chinese version of the Job Content Questionnaire, the Chinese version of the Effort-reward Imbalance Questionnaire, and the Maslach Burnout Inventory for the General Survey, was used to assess occupational stress and job burnout. Independent sample t-test, one-way analysis of variance (ANOVA), correlation analysis, hierarchical multiple regression analysis and logistic regression analysis were used in data analysis. Occupational stress was positively correlated with emotional exhaustion and depersonalization and negatively correlated with personal accomplishment. After adjusting for sociodemographic characteristics, job strain was a risk factor for emotional exhaustion (OR = 2.27, 95% CI: 1.61–3.20) and depersonalization (OR = 1.96 95% CI: 1.45–2.64). Female workers with high effort-reward imbalance had an increased risk of depersonalization (OR = 1.96, 95% CI: 1.33–2.90). Furthermore, female workers with high overcommitment had an increased risk of emotional exhaustion (OR = 3.07, 95% CI: 2.06–4.58) and depersonalization (OR = 2.83, 95% CI: 1.92–4.17), while higher social support reduced the risk of emotional exhaustion (OR = 0.37, 95% CI: 0.26–0.53). The job burnout of female manufacturing workers is significantly correlated with their occupational stress. Higher job strain and overcommitment might be important contributors to job burnout. Increased worker social support can reduce job burnout.
Composite functional movement screen score predicts injuries in youth volleyball players: a prospective cohort study
Authors: Zarei Mostafa , Soltanirad Shabnam , Kazemi Abdolreza , Hoogenboom Barbara J. , Hosseinzadeh Mahdi
Published: November 2022

We aimed to investigate whether composite Functional Movement Screen (FMS) test scores can predict musculoskeletal injuries (MSI) in youth volleyball players. 131 national young volleyball players (Males: n = 100, age = 16.5 years, height = 1.787 m, mass = 68.32 kg; Females: n = 31, age = 13.83 years, height = 1.684 m, mass = 65.12 kg) participated in this prospective cohort study. The FMS screen was performed before starting the season. MSI and exposure data were collected during the season via each team’s certified athletic trainer. The mean FMS score and standard deviation for all volleyball players was 15.85 ± 3.31. A score of ≤ 14 was positive to predict MSI with specificity of 0.60 and sensitivity of 0.93. The odds ratio for (≤ 14/˃14) was 0.048. The relative risk for being injured was 3.46. Positive likelihood ratio was 2.34, and negative likelihood ratio was 0.11. The findings of this study demonstrated that an FMS score of ≤ 14 is an identifiable risk factor for injury in young volleyball players. The FMS can be used as a pre-season screening test to identify volleyball players who may be predisposed to sustaining MSI during the season ahead.
Peripheral blood mononuclear cell phenotype and function are maintained after overnight shipping of whole blood
Authors: Johnson Renee K. , Overlee Brittany L. , Sagen Jessica A. , Howe Charles L.
Published: November 2022

Same day processing of biospecimens such as blood is not always feasible, which presents a challenge for research programs seeking to study a broad population or to characterize patients with rare diseases. Recruiting sites may not be equipped to process blood samples and variability in timing and technique employed to isolate peripheral blood mononuclear cells (PBMCs) at local sites may compromise reproducibility across patients. One solution is to send whole blood collected by routine phlebotomy via overnight courier to the testing site under ambient conditions. Determining the impact of shipping on subsequent leukocyte responses is a necessary prerequisite to any experimental analysis derived from transported samples. To this end, whole blood was collected from healthy control subjects and processed fresh or at 6, 24 and 48 h after collection and handling under modeled shipping conditions. At endpoint, whole blood was assessed via a complete blood count with differential and immunophenotyped using a standardized panel of antibodies [HLADR, CD66b, CD3, CD14, CD16]. PBMCs and neutrophils were isolated from whole blood and subjected to ex vivo stimulation with lipopolysaccharide and heat-killed Staphylococcus aureus. Stimulated release of cytokines and chemokines was assessed by cytometric bead array. RNA was also isolated from PBMCs to analyze transcriptional changes induced by shipping. The complete blood count with differential revealed that most parameters were maintained in shipped blood held for 24 h at ambient temperature. Immunophenotyping indicated preservation of cellular profiles at 24 h, although with broadening of some populations and a decrease in CD16 intensity on classical monocytes. At the transcriptional level, RNAseq analysis identified upregulation of a transcription factor module associated with inflammation in unstimulated PBMCs derived from whole blood shipped overnight. However, these changes were limited in both scale and number of impacted genes. Ex vivo stimulation of PBMCs further revealed preservation of functional responses in cells isolated from shipped blood held for 24 h at ambient temperature. However, neutrophil responses were largely abrogated by this time. By 48 h neither cell population responded within normal parameters. These findings indicate that robust immunophenotyping and PBMC stimulated response profiles are maintained in whole blood shipped overnight and processed within 24 h of collection, yielding results that are representative of those obtained from the sample immediately following venipuncture. This methodology is feasible for many patient recruitment sites to implement and allows for sophisticated immunological analysis of patient populations derived from large geographic areas. With regard to rare disease research, this meets a universal need to enroll patients in sufficient numbers for immunoprofiling and discovery of underlying pathogenic mechanisms.