bluuebunny/crossref_metadata_2025 huggingface dataset:
Cheating in the evaluation. An expedient to estimate the impact of intangibles on the enterprise value of the high-growth start-ups
Authors: Cattafi Giulia , Mariani Giovanna , Pistolesi Francesco , Nicolò Domenico
Published: February 2024

This study investigates the effect of investments in intangible fixed assets and human capital on the Enterprise Value (EV) of Italian high-growth startups (HGSs). To test our hypotheses, we conducted several Ordinary Least Squares (OLS) regression analyses on a dataset comprising 782 HGSs. The EV was esti-mates using the Discounted Cash Flow (DCF) method. Our findings reveal a posi-tive and statistically significant relationship between investments in intangible as-sets and EV. However, investments in human capital and highly skilled workers show a negatively relationship with EV. Lastly, a positive and statistically signifi-cant relationship between value-added per employees and the EV of HGSs has been identified. This study offers valuable insight into the process through which new firms gener-ate value. By strategically investing in intangible assets and human capital, startups not only enhance their probability of survival but also improve their growth potential. This allows these companies to overcome the challenges of the early stage and embark on a sustainable growth process. To spotlight the unique value drivers of these companies, unlike prior studies, we manually estimate the EV. We have employed the DCF method by playing the cards face up: we used the actual cash flows realized by the HGSs during the study period instead of rely-ing on forecasts. We have therefore "cheated" to measure the value created by the HGSs. This research can be considered a pioneering study that significantly con-tributes to the ongoing debate on the value creation process in fast growing startups.
Interpersonal violence against children in sport in the Italian context: prevalence research
Authors: Ferracuti Stefano , Barchielli Benedetta , Hartill Mike , Simonetti Daniela
Published: February 2024

The current article presents the results of the first comprehensive prevalence study focusing on interpersonal violence against children in the context of sports in Italy. Utilizing a dedicated online questionnaire, our survey encompassed a cohort of over 1.400 adults who had engaged in organized sports activities before reaching the age of 18. The inquiry sought to elicit information regarding their experiences with childhood psychological, physical, and sexual violence within the sporting milieu. The survey outcomes revealed noteworthy statistics, with 30% of all respondents reporting incidents of psychological violence, 18% disclosing experiences of physical violence, 14% reported neglect and 14% indicating encounters with sexual violence during their participation in sports. Some of this data and their discussion has already been included in the Change the Game project's final research report. These findings can be used as a fundamental foundation for monitoring and assessing current and future protective measures in the context of sports in Italy.
Prevenire e contrastare l'abuso sui minorenni in ambito sportivo: una overview delle più diffuse best practices
Authors: Marchetti Daniela , Ceravolo Francesco , D’Ettorre Melissa , Di Benedetto Sonia , Verrocchio Maria Cristina
Published: February 2024

Nei contesti sportivi i minori possono essere a rischio di subire diverse forme di maltratta-mento e abuso. L'articolo fornisce una panoramica delle principali iniziative nazionali e in-ternazionali di prevenzione e contrasto del fenomeno, al fine di delineare delle best practi-ces, ovvero un insieme di condotte volte a garantire un ambiente sicuro in cui praticare sport. Le principali buone pratiche emerse dall'analisi dei documenti riguardano interventi di formazione e sensibilizzazione, misure di reclutamento degli operatori sportivi, adesione ad un codice etico e di condotta, procedure di segnalazione, supervisione generale e sicurez-za, istituzione di gruppi di lavoro interdisciplinari. Le iniziative sono state spesso limitate a singoli interventi o specifici settori sportivi, mettendo in luce la necessità crescente di intra-prendere azioni comuni e condivise.
Group attachment and its inner working model Developing a projective test to measure mental representations of group attachment based on the AAP
Authors: Iuga Christine
Published: February 2024

Is there any difference between dyadic and group attachment? Following Bowlby's (1982) beliefs, attachment is important across the lifespan: dependent on the early sensitive caregiving, we seek out for others ( family members, peer groups and lovers) to fulfill our different needs. The refined mental representations also include our experiences of receiving protection and care in groups and influence our perception and action in future situations. Based upon the AAP (George, 1999), which provides a developmental approach to the assessment of the dyadic adult attachment system, this study tries to extend the projective test by measuring patterns of group attachment. The AGAP-Test (Adult Group Attachment Projective Picture Test) contains a series of eight pictures that activate the unconscious "group attachment system" and tries to give via patients narrative insight in secure, insecure or disorganized schemes and defensive processes against anxiety, suffering and pain in repeated former experiences in groups. The AGAP Test is currently in development and used in the measurement of the change of group attachment related mental representations in individuals during long-term psychodynamic group therapy. The second approach tries to give insight into attachment related social unconscious processes such as defense and coherence via guiding the "group as unity" to absolve the projective test. For the "healthy" reference groups, the narratives of eight group analytic trainee groups at the GRAS (Gruppenanalyseseminar e.V.) Institute in Bonn, Germany, have been collected. To illustrate the effectiveness of aspects relevant to group attachment, the test is also frequently used in the supervision and further training of adult student groups.
Richard Lipsey and the "Tyranny" of a Unique Labour Market Equilibrium
Authors: Palumbo Antonella
Published: February 2024

The article discusses Richard Lipsey's (2000a, 2000b, 2010, 2016) criticism of the uniqueness of the macroeconomic equilibrium at constant inflation postulated by new-classical macroeconomic models. Lipsey's position is analysed in the light of his early contribution to the debate on the Phillips curve (Lipsey 1960). There, as later, Lipsey's argument rests on the assumption that the labour market, though characterised by a unique demand-and-supply equilibrium, may persist in disequilibria in the long run. Such proposition is discussed critically. Lipsey's analysis can be seen as a clear expression of the fundamental theoretical difficulty in reconciling Keynesian macroeconomic analysis with the neoclassical postulates.
How the Cryptocurrency Discourse is Changing: A Textual Analysis
Authors: Tusset Gianfranco
Published: February 2024

The paper aims to retrace the academic discourse on cryptocurrencies from 2015 to 2022 by treating it as a lexical unicum that evolves over time. The purpose is to understand what themes have emerged and how they have changed the discourse on cryptocurrencies. We used a three-step methodology. The first consists of text mining that allows us to create, from 1057 academic articles on the subject, the matrix containing the frequencies of words/n-grams. In a second step, lexical analysis is enriched by correspondence analysis, a useful tool to measure the "distance" and evolution of academic discourse and to identify significant content discontinuity. Finally, the causal analysis addresses the ultimate goal of understanding whether it is possible to define future developments in the cryptocurrency discourse, whether it will absorb instances from outside or remain focused on the prevailing themes to date. The identification and application of a method to analyze the evolution of the cryptocurrency discourse allowed us to distinguish at least two distinct phases characterized by specific content and cryptocurrencies.
Impact of Ambient Temperature, Passenger Load, and Delay on the Consumption of Battery Electric Buses
Authors: Szilassy Péter Ákos , Földes Dávid
Published: February 2024

The operation of state-of-the-art battery electric buses (BEBs) has started recently, and their consumption model is unknown. Therefore, the service providers are lenient regarding the energy used. Our aim was to reveal the effects of ambient temperature and bus service characteristics, such as passenger load and delay, on the energy consumption. Real-time consumption data of BEBs were analyzed in Nyíregyháza, Hungary, and the functional relationships among the aforementioned variables were revealed. We found that while ambient temperature is negatively correlated with consumption in the cold winter periods, the consumption surplus is positively correlated with passenger load and generally positively correlated with the delay on the trip because of road traffic. In the case of delay, the consumption increase is caused by more frequent acceleration and the greater consumption of auxiliary systems due to longer running times. Accordingly, the energy consumption can be estimated if the characteristics data are available. The results can be used by bus service operators to plan the daily schedule and predict the energy consumption of a BEB.
Causas de trastornos musculoesqueléticos en los trabajadores del área de la construcción Cuenca – Ecuador
Authors: Quizhpi Urgilés Ronald Darío , Quinde Alvear Ángel Giovanny
Published: February 2024

La investigación parte de los trastornos musculoesqueléticos que experimenta el área de la construcción. Se propone establecer cuáles son las causas relacionadas a los trastornos musculoesqueléticos en los trabajadores del área de la construcción Cuenca- Ecuador. El estudio es cuantitativo y elogia del constructo teórico en donde la carga laboral está asociada con los trastornos musculoesqueléticos. Se investigó a 41 personas de la constructora Flores. Los resultados revelan que existe correlación negativa entre la carga laboral con -0,353* siendo las pruebas estadísticamente significativas a un nivel menor al p-valor de 0,05.  La variable antecedentes médicos no pasó la prueba estadística con un coeficiente de correlación -0,064. Se concluye que, la carga laboral es un componente de peligro que afecta no solo a la salud física, sino también a la salud mental de los trabajadores, involucrando la calidad de trabajo que desempeñan diariamente los colaboradores que son el contexto de estudio. Introducción.  Los trastornos musculoesqueléticos comienzan en su forma más leve, manifestándose inicialmente como un dolor ocasional, y pueden evolucionar hacia un estado más grave y bien definido. Este dolor puede surgir como consecuencia de una carga de trabajo excesiva o servir como un indicio del comienzo de una enfermedad. Este hecho nos demuestra que las lesiones del sistema musculoesquelético están teniendo un impacto considerable y en aumento en todo el mundo, siendo la principal causa de dolor y discapacidad. Objetivo. Establecer cuáles son las causas relacionadas a los trastornos musculoesqueléticos en los trabajadores del área de la construcción, Cuenca Ecuador. Metodología. Es de tipo cuantitativo porque se recolectarán datos que serán procesadas mediante técnicas estadísticas descriptivas, que permitirá establecer la relación entre las variables del estudio y comprender cuales son las causas de trastornos musculoesqueléticos en los trabajadores de la construcción. Resultados. Los resultados obtenidos de las variables de investigación son estadísticamente significativos al ser menores al p-valor 0,05. Lo fundamentado está dentro de la variable Prom_Carga laboral presenta una correlación negativa de (- 0,353*) obtenida a partir del estudio realizado. Conclusión.  La carga laboral es un factor primordial que genera estrés en el ámbito laboral, y está estrechamente vinculada al tipo de labor o profesión que desempeñan los empleados, así como al nivel de exigencias físicas, mentales y temporales necesarios para llevar a cabo las tareas requeridas en sus respectivos puestos de trabajo
EFFICIENCY OF PUBLIC-PRIVATE PARTNERSHIP IN INFRASTRUCTURE DEVELOPMENT: ANALYSIS AND PROSPECTS
Authors: BATRYMENKO OLEG , MELNYK VIKTOR
Published: February 2024

In 2022, the magnitude of investments in Public-Private Partnerships (PPP) within the infrastructure sector demonstrated a gradual resurgence. Beyond the well-established practice of attracting significant PPP investments in developed nations, there has been a notable increase in the engagement of middle-income countries in the utilization of public-private collaborative mechanisms for the advancement of their infrastructure. Among the sectors, transportation, and communications have consistently maintained a prominent position in terms of both investment influx and the quantity of successfully executed infrastructure projects on a global scale. Quantitative performance indicators within the sphere of PPP projects, encompassing metrics such as the count, monetary volume, and the proportion of different agreement types, manifest encouraging trends in the execution of infrastructure PPP initiatives. Conversely, the qualitative outcomes of this investigation reveal a spectrum of issues that are intrinsically linked to CSFs. These CSFs represent the principal benchmarks that exert a direct influence on the efficiency of PPP projects concerning their established objectives, processes, and management framework. The research undertaken by the authors has successfully identified a range of disparities in the challenges faced during the implementation of PPP projects across diverse nations, notwithstanding the similarity in the underlying mechanisms of cooperation.
PEDAGOGICAL SYSTEM FOR FORMING THE SOCIAL HEALTH OF CHILDREN AND YOUTH
Authors: TSYBANYUK OLEKSANDRA , SLYUSARENKO NINA , KUZMENKO VASYL , TYMCHUK LIUDMYLA
Published: February 2024

The present academic paper is devoted to developing and implementing educational systems for the formation of social health of children and youth. Social health is defined in this context as a multifaceted concept that includes social skills, emotional intelligence, stress management, civic responsibility and tolerance. The primary purpose of the present research is to develop a pedagogical system that would contribute to forming and maintaining the social health of children and youth. Pedagogical approaches in the education system are distinguished, namely: psychological and pedagogical, socio-cultural, health-preserving, interactive, ecological and gender approaches. It has been determined that the formation of children’s social health is ensured through such aspects as the development of social skills by means of interactive activities and group work, training of emotional intelligence through professional exercises and learning stress management methods. The conducted research provides a valuable scientific and practical elaboration in the field of developing and implementing educational approaches to the formation of social health of children and youth. It has been emphasized that the established educational system for forming the social health of children and youth is comprehensive and systematic.
Toward a Regime of Emotional Authenticity: Eileen Chang’s Literary Transmediation of Theater and Cinema in Two 1940s Love Stories
Authors: YANG Renren
Published: February 2024

This essay examines Eileen Chang’s transmedial theater and cinema in two 1940s love stories and draws attention to the historical transformation of the emotional regime underlying these literary reworkings. By canvassing the theatrical impulses in “Love in a Fallen City” (1943) and the cinematic residues in “So Much Regret” (1947), this essay argues that Chang’s depictions of romantic relationships in 1940s Shanghai suggest an incompleteness of what Eva Illouz calls the “great transformation of love” from a regime of ritualized emotions to one of emotional authenticity in Late Imperial and Republican China. The essay also demonstrates how the great transformation of love is gendered: what Chang underscores is the modern woman’s lack of “moral clarity” in her pursuit of love as a result of the painful clash between a theater-based presentational style and a cinema-based representational style of affective communication.
Deep learning classification for macrophage subtypes through cell migratory pattern analysis
Authors: Kesapragada Manasa , Sun Yao-Hui , Zlobina Ksenia , Recendez Cynthia , Fregoso Daniel , Yang Hsin-Ya , Aslankoohi Elham , Isseroff Rivkah , Rolandi Marco , Zhao Min , Gomez Marcella
Published: February 2024

Macrophages can exhibit pro-inflammatory or pro-reparatory functions, contingent upon their specific activation state. This dynamic behavior empowers macrophages to engage in immune reactions and contribute to tissue homeostasis. Understanding the intricate interplay between macrophage motility and activation status provides valuable insights into the complex mechanisms that govern their diverse functions. In a recent study, we developed a classification method based on morphology, which demonstrated that movement characteristics, including speed and displacement, can serve as distinguishing factors for macrophage subtypes. In this study, we develop a deep learning model to explore the potential of classifying macrophage subtypes based solely on raw trajectory patterns. The classification model relies on the time series of x-y coordinates, as well as the distance traveled and net displacement. We begin by investigating the migratory patterns of macrophages to gain a deeper understanding of their behavior. Although this analysis does not directly inform the deep learning model, it serves to highlight the intricate and distinct dynamics exhibited by different macrophage subtypes, which cannot be easily captured by a finite set of motility metrics. Our study uses cell trajectories to classify three macrophage subtypes: M0, M1, and M2. This advancement holds promising implications for the future, as it suggests the possibility of identifying macrophage subtypes without relying on shape analysis. Consequently, it could potentially eliminate the necessity for high-quality imaging techniques and provide more robust methods for analyzing inherently blurry images.
Socioeconomic status as a predictor of post-operative mortality and outcomes in carotid artery stenting vs. carotid endarterectomy
Authors: Baxi Jigesh , Chao Joshua C. , Dewan Krish , Yang NaYoung K. , Pepe Russell J. , Deng Xiaoyan , Soliman Fady K. , Volk Lindsay , Rahimi Saum , Russo Mark J. , Lee Leonard Y.
Published: February 2024

Background

The association between low socioeconomic status (SES) and worse surgical outcomes has become an emerging area of interest. Literature has demonstrated that carotid artery stenting (CAS) poses greater risk of postoperative complications, particularly stroke, than carotid endarterectomy (CEA). This study aims to compare the impact of low SES on patients undergoing CAS vs. CEA.

Methods

The National Inpatient Sample (NIS) was queried for patients undergoing CAS and CEA from 2010 to 2015. Patients were stratified by highest and lowest median income quartiles by zip code and compared through demographics, hospital characteristics, and comorbidities defined by the Charlson Comorbidity Index (CCI). Primary outcome was in-hospital mortality. Secondary outcomes included acute kidney injury (AKI), post-operative stroke, sepsis, and bleeding requiring reoperation.Multivariable logistic regression was used to determine the effect of SES on outcomes.

Results

Five thousand four hundred twenty-five patients underwent CAS (Low SES: 3,516 (64.8%); High SES: 1,909 (35.2%) and 38,399 patients underwent CEA (Low SES: 22,852 (59.5%); High SES: 15,547 (40.5%). Low SES was a significant independent predictor of mortality [OR = 2.07 (1.25–3.53); p = 0.005] for CEA patients, but not for CAS patients [OR = 1.21 (CI 0.51–2.30); p = 0.68]. Stroke was strongly associated with low SES, CEA patients (Low SES = 1.5% vs. High SES = 1.2%; p = 0.03), while bleeding was with high SES, CAS patients (Low SES = 5.3% vs. High SES = 7.1%; p = 0.01). CCI was a strong predictor of mortality for both procedures [CAS: OR1.45 (1.17–1.80); p < 0.001. CEA: OR1.60 (1.45–1.77); p < 0.001]. Advanced age was a predictor of mortality post-CEA [OR = 1.03 (1.01–1.06); p = 0.01]. While not statistically significant, advanced age and increased mortality trended towards a positive association in CAS [OR = 1.05 (1.00–1.10); p = 0.05].

Conclusions

Low SES is a significant independent predictor of post-operative mortality in patients who underwent CEA, but not CAS. CEA is also associated with higher incidence of stroke in low SES patients. Findings demonstrate the impact of SES on outcomes for patients undergoing carotid revascularization procedures. Prospective studies are warranted to further evaluate this disparity.
Machine learning analysis and nowcasting of marine fog visibility using FATIMA Grand Banks campaign measurements
Authors: Gultepe Eren , Wang Sen , Blomquist Byron , Fernando Harindra J. S. , Kreidl O. Patrick , Delene David J. , Gultepe Ismail
Published: February 2024

Introduction: This study presents the application of machine learning (ML) to evaluate marine fog visibility conditions and nowcasting of visibility based on the FATIMA (Fog and turbulence interactions in the marine atmosphere) campaign observations collected during July 2022 in the North Atlantic in the Grand Banks area and vicinity of Sable Island, northeast of Canada.

Methods: The measurements were collected using instrumentation mounted on the Research Vessel Atlantic Condor. The collected meteorological parameters were: visibility (Vis), precipitation rate, air temperature, relative humidity with respect to water, pressure, wind speed, and direction. Using all variables, the droplet number concentration was used to qualitatively indicate and assess characteristics of the fog using the t-distributed stochastic neighbor embedding projection method (t-SNE), which clustered the data into groups. Following t-SNE analysis, a correlation heatmap was used to select relevant meteorological variables for visibility nowcasting, which were wind speed, relative humidity, and dew point depression. Prior to nowcasting, the input variables were preprocessed to generate additional time-lagged variables using a 120-minute lookback window in order to take advantage of the intrinsic time-varying features of the time series data. Nowcasting of Vis time series for lead times of 30 and 60 minutes was performed using the ML regression methods of support vector regression (SVR), least-squares gradient boosting (LSB), and deep learning at visibility thresholds of Vis < 1 km and < 10 km.

Results: Vis nowcasting at the 60 min lead time was best with LSB and was significantly more skillful than persistence analysis. Specifically, using LSB the overall nowcasts at Vis 1 < km and Vis 10 < km were RMSE = 0.172 km and RMSE = 2.924 km, respectively. The nowcasting skill of SVR for dense fog (Vis ≤ 400 m) was significantly better than persistence at all Vis thresholds and lead times, even when it was less skillful than persistence at predicting high visibility.

Discussion: Thus, ML techniques can significantly improve Vis prediction when either observations or modelbased accurate time-dependent variables are available. The results suggest that there is potential for future ML analysis that focuses on modeling the underlying factors of fog formation.
Evaluation of climate change impact on plants and hydrology
Authors: Shah Ishaq Ali , Khan Haroon , Muhammad Zahir , Ullah Rehman , Iqbal Shahid , Nafidi Hiba-Allah , Bourhia Mohammed , Salamatullah Ahmad Mohammad
Published: February 2024

Climate change (CC) is the menace of the hour impacting every facet of human existence. Regional CC and its impact studies are crucial in that they contribute to global change. The current study aims to investigate the prevalence of CC in Charsadda, Pakistan and its impact on vegetation and hydrology of the region to understand microclimate variability contribution to global CC. Utilizing local climate data for 20 years (2001–2020), Modified Mann-Kendall and Sen’s Slope statistics were employed to determine monthly and seasonal trends in climate variables. Significant changing climate variables were regressed on Moderate resolution Imaging Spectroradiometer (MODIS) satellite dataset viz. normalized difference vegetation index (NDVI). Due to the prominent climate factor impacting vegetation, NDVI was further correlated to MODIS land surface temperature (LST). Floods being the conspicuous climate calamity were mapped for 2005 and 2010 using satellites Landsat 5 and 7 dataset viz. normalized difference water index (NDWI) with flood risk assessment by watershed delineation. The findings revealed significant (p < 0.05) variability in climate variables (average monthly and summer maximum temperature, and average monthly and summer precipitation) that are driving CC and impacting vegetation and hydrology in the region. Temperature and solar radiation affect NDVI adversely while precipitation and relative humidity has positive impact on vegetation. NDVI varied greatly spatiotemporally, often increasing but worsening in some areas (Shabqadar, Abazai, Palai and Charsadda city with NDVI = 0.1–0.3) of the study region as a result of extreme weather events. Temporally, NDVI improved with an overall positive trend with a stage (2007–2016) of noticeable zigzag fluctuation. Spatial grids with higher LST (>40°C) were either devoid of or with sparse NDVI (<0.3) presenting global warming as peril to vegetation. NDWI maps (2005, 2010 floods) indicate that after floods wreaked havoc on the region altering the vegetation pattern revealing heavy irregular precipitation as the next to temperature in jeopardizing vegetation of the region. Lower elevation regions along the Swat and Kabul Rivers with a greater risk of flooding were identified by watershed delineation. The study suggests that local governments and stakeholders implement CC mitigation strategies and plans for vegetation restoration, flood alerts with post-flood management for regional sustainable development.
The impacts of host traits on parasite infection of montane birds in southwestern China
Authors: Zhan Xia , Huang Xi , Pagani-Núñez Emilio , Tang Qindong , Ho Heiman , Zhou Wenjun , Liu Yang , Liang Dan
Published: February 2024

Parasitic infections have the potential to impact the hosts’ body condition, elevate physiological responses, and ultimately lead to increased mortality. Host-parasite interactions are tied to the ecological and life-history traits of the hosts. While montane birds are susceptible to avian blood parasites, few studies have simultaneously assessed how inter- and intra-specific traits of hosts influence their probability of parasite infection. In this study, we screened for avian blood parasites across 214 individuals from 51 species at two sites, including a lowland farmland at 700 m and a highland forest at 2,500 m, in the Gaoligong Mountains in southwestern China. Overall blood parasite prevalence was 53.74%, with divergent species-specific prevalence ranging from 6.25% to 66.67%. We also measured traits indicative of body condition and physiological responses of each sampled individual. Using Bayesian phylogenetic logistic models, we assessed whether parasite infection probability is associated with ecological and life history traits of host species. Larger bird species were more likely to be infected than smaller bird species, and omnivore species showed lower susceptibility than those with other diets such as insectivores and herbivores. In contrast, foraging strata, nest type, and participation in mixed-species flocks of host species did not affect infection probability. We then used a reduced sample of eight species with more than five individuals, to assess the associations between intra-specific infection probability and host body condition, represented by fat and muscle reserves, and acute stress responses measured through breath rate. While infected individuals were likely to have more fat reserves than non-infected individuals, we did not find any association between infection probability and muscle reserve and body mass, nor with breath rate. Our results revealed that at the species level, specific traits (body mass and diet) of host species predict infection probability and implied a potential link at the individual level between enhanced body condition and increased resilience to parasite infection.
Mitochondrial and apicoplast genome copy abundances of haemosporidian parasites are explained by host species and parasitic lineage
Authors: Brandler Tim , Chakarov Nayden
Published: February 2024

Endosymbiotic organelles, such as mitochondria and plastids, contain own remnant genomes (nucleoids), whose variable abundance in cells may be adaptive to the physiological necessities and functions of the cells. Unicellular apicomplexan parasites contain one mitochondrium and one apicoplast with variable genome copy numbers. We measured the abundance of mitochondrial, apicoplast and nuclear genome copies in a set of avian blood samples infected with haemosporidian blood parasites, belonging to the three main genera Plasmodium, Haemoproteus and Leucocytozoon. We designed general primers suitable for qPCR, amplifying fragments of the mitogenome, plastome and nuclear genomes of avian malaria and related haemosporidian parasites. We measured the amplification of these fragments in 153 samples of 23 avian host species and infected with 33 parasitic lineages. We estimate on average several hundred mitochondrial genome copies and several tens of apicoplast copies per haploid gametocyte cell with substantial variation among samples. Host species appeared to differ in their mitogenome abundance while parasitic lineages differed in plastome abundance per cell (per nuclear copy signal). We did not find consistent differences between parasite genera or higher avian taxa. Parasite lineages and host bird species did not differ consistently in infection intensity, estimated from parasite to host nuclear signals, which may indicate that samples were taken at different stages of infection. However, this and similar results remain to be cross-validated with in-situ imaging techniques. The novel molecular tools introduced here offer avenues for the characterization of nucleoid abundance of haemosporidian parasites over environmental conditions and parasitic developmental stages. Such measures will improve our understanding of parasite physiology, ecology, the coadaptation and coevolution with hosts and suggest possible augmentations to standard methods in the research field.
A gene regulatory network model that recovers the abaxial-adaxial polarity in Arabidopsis thaliana leaf primordium
Authors: Yuste Mariana , Piñeyro-Nelson Alma , Azpeitia Eugenio
Published: February 2024

Megaphylls, present in the majority of vascular plants, show in many plant lineages an abaxial-adaxial polarity in their dorsoventral axis. This polarity commonly translates into different tissues developing on each side of the leaf blade. This is important because it promotes better photosynthetic efficiency as related to light absorption and gas exchange. Many researchers have studied the molecular bases of the emergence of leaf abaxial-adaxial polarity, showing that it is produced by the interaction and differential expression of particular genes and other molecules. However, until now, it is still unclear if the molecular components documented thus far are sufficient to explain the emergence of leaf polarity. In this work, we integrated the available experimental data to construct a graph of the Gene Regulatory Network (GRN) involved in the formation of abaxial-adaxial polarity in the leaf primordium of Arabidopsis thaliana. This graph consisted of 21 nodes and 47 regulations. We extracted the main components of the graph to obtain a Minimum Network consisting of six genes and 22 possible regulations. Then, we used the Boolean network (BN) formalism to describe the dynamics of this Minimum Network. We identified 1905 distinct BNs that comprised the regulations of the Minimum Network and exclusively generated the two attractors representing the abaxial and adaxial cell types. This highlights the fact that most graphs, including our network, can describe experimentally observed behaviors with many BN dynamics. By performing mutant simulations and robustness analysis, we found that two of the 1905 BNs better reproduce experimentally available information. To produce the expected attractors, both BNs predict the same missing regulations, which we propose should be experimentally analyzed to confirm their existence. Interestingly, these two BNs have low robustness to perturbations compared with previously analyzed GRNs. This was an unexpected result since abaxial-adaxial polarity is a robust biological trait, which suggests more components or regulations of the network are missing.
Immune mapping of human tuberculosis and sarcoidosis lung granulomas
Authors: Carow Berit , Muliadi Victoria , Skålén Kristina , Yokota Chika , Kathamuthu Gokul Raj , Setiabudiawan Todia Pediatama , Lange Christoph , Scheu Katrin , Gaede Karoline I. , Goldmann Torsten , Pandita Ankur , Masood Kiran Iqbal , Pervez Shahid , Grunewald Johan , Hasan Zahra , Levin Max , Rottenberg Martin E.
Published: February 2024

Tuberculosis (TB) and sarcoidosis are both granulomatous diseases. Here, we compared the immunological microenvironments of granulomas from TB and sarcoidosis patients using in situ sequencing (ISS) transcriptomic analysis and multiplexed immunolabeling of tissue sections. TB lesions consisted of large necrotic and cellular granulomas, whereas “multifocal” granulomas with macrophages or epitheloid cell core and a T-cell rim were observed in sarcoidosis samples. The necrotic core in TB lesions was surrounded by macrophages and encircled by a dense T-cell layer. Within the T-cell layer, compact B-cell aggregates were observed in most TB samples. These B-cell clusters were vascularized and could contain defined B-/T-cell and macrophage-rich areas. The ISS of 40–60 immune transcripts revealed the enriched expression of transcripts involved in homing or migration to lymph nodes, which formed networks at single-cell distances in lymphoid areas of the TB lesions. Instead, myeloid-annotated regions were enriched in CD68, CD14, ITGAM, ITGAX, and CD4 mRNA. CXCL8 and IL1B mRNA were observed in granulocytic areas in which M. tuberculosis was also detected. In line with ISS data indicating tertiary lymphoid structures, immune labeling of TB sections expressed markers of high endothelial venules, follicular dendritic cells, follicular helper T cells, and lymph-node homing receptors on T cells. Neither ISS nor immunolabeling showed evidence of tertiary lymphoid aggregates in sarcoidosis samples. Together, our finding suggests that despite their heterogeneity, the formation of tertiary immune structures is a common feature in granulomas from TB patients.
T follicular helper cells expansion in transplant recipients correlates with graft infiltration and adverse outcomes
Authors: Désy Olivier , Béland Stéphanie , Thivierge Marie-Pier , Marcoux Meagan , Desgagnés Jean-Simon , Bouchard-Boivin François , Gama Alcino , Riopel Julie , Latulippe Eva , De Serres Sacha A.
Published: February 2024

Introduction

The process of immunization following vaccination in humans bears similarities to that of immunization with allografts. Whereas vaccination aims to elicit a rapid response, in the transplant recipient, immunosuppressants slow the immunization to alloantigens. The induction of CD4+CXCR5+ T follicular helper (Tfh) cells has been shown to correlate with the success of vaccine immunization.

Method

We studied a cohort of 65 transplant recipients who underwent histological evaluation concurrent with PBMC isolation and follow-up sampling to investigate the phenotypic profiles in the blood and allotissue and analyze their association with clinical events.

Results

The proportion of circulating Tfh cells was heterogeneous over time. Patients in whom this compartment increased had lower CCR7-PD1+CD4+CXCR5+ T cells during follow-up. These patients exhibited more alloreactive CD4+ T cells using HLA-DR-specific tetramers and a greater proportion of detectable circulating plasmablasts than the controls. Examination of baseline biopsies revealed that expansion of the circulating Tfh compartment did not follow prior intragraft leukocyte infiltration. However, multicolor immunofluorescence microscopy of the grafts showed a greater proportion of CXCR5+ T cells than in the controls. CD4+CXCR5+ cells were predominantly PD1+ and were in close contact with B cells in situ. Despite clinical stability at baseline, circulating Tfh expansion was associated with a higher risk of a composite of anti-HLA donor-specific antibodies, rejection, lower graft function, or graft loss.

Conclusion

In otherwise stable patients post-transplant, circulating Tfh expansion can identify ongoing alloreactivity, detectable before allograft injury. Tfh expansion is relevant clinically because it predicts poor graft prognosis. These findings have implications for immune surveillance.
A genome-wide association study on hematopoietic stem cell transplantation reveals novel genomic loci associated with transplant outcomes
Authors: Rosenberger Albert , Crossland Rachel E. , Dressel Ralf , Kube Dieter , Wolff Daniel , Wulf Gerald , Bickeböller Heike , Dickinson Anne , Holler Ernst
Published: February 2024

Introduction

Data on genomic susceptibility for adverse outcomes after hematopoietic stem cell transplantation (HSCT) for recipients are scarce.

Methods

We performed a genome wide association study (GWAS) to identify genes associated with survival/mortality, relapse, and severe graft-versus-host disease (sGvHD), fitting proportional hazard and subdistributional models to data of n=1,392 recipients of European ancestry from three centres.

Results

The single nucleotide polymorphism (SNP) rs17154454, intronic to the neuronal growth guidant semaphorin 3C gene (SEMA3C), was genome-wide significantly associated with event-free survival (p=7.0x10-8) and sGvHD (p=7.5x10-8). Further associations were detected for SNPs in the Paxillin gene (PXN) with death without prior relapse or sGvHD, as well as for SNPs of the Plasmacytoma Variant Translocation 1 gene (PVT1, a long non-coding RNA gene), the Melanocortin 5 Receptor (MC5R) gene and the WW Domain Containing Oxidoreductase gene (WWOX), all associated with the occurrence of sGvHD. Functional considerations support the observed associations.

Discussion

Thus, new genes were identified, potentially influencing the outcome of HSCT.
Redox processes are major regulators of leukotriene synthesis in neutrophils exposed to bacteria Salmonella typhimurium; the way to manipulate neutrophil swarming
Authors: Golenkina Ekaterina A. , Viryasova Galina M. , Galkina Svetlana I. , Kondratenko Natalia D. , Gaponova Tatjana V. , Romanova Yulia M. , Lyamzaev Konstantin G. , Chernyak Boris V. , Sud’ina Galina F.
Published: February 2024

Neutrophils play a primary role in protecting our body from pathogens. When confronted with invading bacteria, neutrophils begin to produce leukotriene B4, a potent chemoattractant that, in cooperation with the primary bacterial chemoattractant fMLP, stimulates the formation of swarms of neutrophils surrounding pathogens. Here we describe a complex redox regulation that either stimulates or inhibits fMLP-induced leukotriene synthesis in an experimental model of neutrophils interacting with Salmonella typhimurium. The scavenging of mitochondrial reactive oxygen species by mitochondria-targeted antioxidants MitoQ and SkQ1, as well as inhibition of their production by mitochondrial inhibitors, inhibit the synthesis of leukotrienes regardless of the cessation of oxidative phosphorylation. On the contrary, antioxidants N-acetylcysteine and sodium hydrosulfide promoting reductive shift in the reversible thiol-disulfide system stimulate the synthesis of leukotrienes. Diamide that oxidizes glutathione at high concentrations inhibits leukotriene synthesis, and the glutathione precursor S-adenosyl-L-methionine prevents this inhibition. Diamide-dependent inhibition is also prevented by diphenyleneiodonium, presumably through inhibition of NADPH oxidase and NADPH accumulation. Thus, during bacterial infection, maintaining the reduced state of glutathione in neutrophils plays a decisive role in the synthesis of leukotriene B4. Suppression of excess leukotriene synthesis is an effective strategy for treating various inflammatory pathologies. Our data suggest that the use of mitochondria-targeted antioxidants may be promising for this purpose, whereas known thiol-based antioxidants, such as N-acetylcysteine, may dangerously stimulate leukotriene synthesis by neutrophils during severe pathogenic infection.
Epstein-Barr virus: the mastermind of immune chaos
Authors: Silva Jean de Melo , Alves Carlos Eduardo de Castro , Pontes Gemilson Soares
Published: February 2024

The Epstein-Barr virus (EBV) is a ubiquitous human pathogen linked to various diseases, including infectious mononucleosis and multiple types of cancer. To control and eliminate EBV, the host’s immune system deploys its most potent defenses, including pattern recognition receptors, Natural Killer cells, CD8+ and CD4+ T cells, among others. The interaction between EBV and the human immune system is complex and multifaceted. EBV employs a variety of strategies to evade detection and elimination by both the innate and adaptive immune systems. This demonstrates EBV’s mastery of navigating the complexities of the immunological landscape. Further investigation into these complex mechanisms is imperative to advance the development of enhanced therapeutic approaches with heightened efficacy. This review provides a comprehensive overview of various mechanisms known to date, employed by the EBV to elude the immune response, while establishing enduring latent infections or instigate its lytic replication.
Comparative transcriptome analysis of T lymphocyte subpopulations and identification of critical regulators defining porcine thymocyte identity
Authors: Han Pingping , Zhang Wei , Wang Daoyuan , Wu Yalan , Li Xinyun , Zhao Shuhong , Zhu Mengjin
Published: February 2024

Introduction

The development and migration of T cells in the thymus and peripheral tissues are crucial for maintaining adaptive immunity in mammals. However, the regulatory mechanisms underlying T cell development and thymocyte identity formation in pigs remain largely underexplored.

Method

Here, by integrating bulk and single-cell RNA-sequencing data, we investigated regulatory signatures of porcine thymus and lymph node T cells.

Results

The comparison of T cell subpopulations derived from porcine thymus and lymph nodes revealed that their transcriptomic differences were influenced more by tissue origin than by T cell phenotypes, and that lymph node cells exhibited greater transcriptional diversity than thymocytes. Through weighted gene co-expression network analysis (WGCNA), we identified the key modules and candidate hub genes regulating the heterogeneity of T cell subpopulations. Further, we integrated the porcine thymocyte dataset with peripheral blood mononuclear cell (PBMC) dataset to systematically compare transcriptomic differences between T cell types from different tissues. Based on single-cell datasets, we further identified the key transcription factors (TFs) responsible for maintaining porcine thymocyte identity and unveiled that these TFs coordinately regulated the entire T cell development process. Finally, we performed GWAS of cell type-specific differentially expressed genes (DEGs) and 30 complex traits, and found that the DEGs in thymus-related and peripheral blood-related cell types, especially CD4_SP cluster and CD8-related cluster, were significantly associated with pig productive and reproductive traits.

Discussion

Our findings provide an insight into T cell development and lay a foundation for further exploring the porcine immune system and genetic mechanisms underlying complex traits in pigs.
Myeloid and dendritic cells enhance therapeutics-induced cytokine release syndrome features in humanized BRGSF-HIS preclinical model
Authors: Martin Gaëlle H. , Gonon Alexis , Martin-Jeantet Perrine , Renart-Depontieu Florence , Biesova Zuzana , Cifuentes Anokhi , Mukherjee Arnab , Thisted Thomas , Doerner Astrid , Campbell Dean O. , Bourré Ludovic , van der Horst Edward H. , Rezza Amélie , Thiam Kader
Published: February 2024

Objectives

Despite their efficacy, some immunotherapies have been shown to induce immune-related adverse events, including the potentially life-threatening cytokine release syndrome (CRS), calling for reliable and translational preclinical models to predict potential safety issues and investigate their rescue. Here, we tested the reliability of humanized BRGSF mice for the assessment of therapeutics-induced CRS features in preclinical settings.

Methods

BRGSF mice reconstituted with human umbilical cord blood CD34+ cells (BRGSF-CBC) were injected with anti-CD3 antibody (OKT3), anti-CD3/CD19 bispecific T-cell engager Blinatumomab, or VISTA-targeting antibody. Human myeloid and dendritic cells’ contribution was investigated in hFlt3L-boosted BRGSF-CBC mice. OKT3 treatment was also tested in human PBMC-reconstituted BRGSF mice (BRGSF-PBMC). Cytokine release, immune cell distribution, and clinical signs were followed.

Results

OKT3 injection in BRGSF-CBC mice induced hallmark features of CRS, specifically inflammatory cytokines release, modifications of immune cell distribution and activation, body weight loss, and temperature drop. hFlt3L-boosted BRGSF-CBC mice displayed enhanced CRS features, revealing a significant role of myeloid and dendritic cells in this process. Clinical CRS-managing treatment Infliximab efficiently attenuated OKT3-induced toxicity. Comparison of OKT3 treatment’s effect on BRGSF-CBC and BRGSF-PBMC mice showed broadened CRS features in BRGSF-CBC mice. CRS-associated features were also observed in hFlt3L-boosted BRGSF-CBC mice upon treatment with other T-cell or myeloid-targeting compounds.

Conclusions

These data show that BRGSF-CBC mice represent a relevant model for the preclinical assessment of CRS and CRS-managing therapies. They also confirm a significant role of myeloid and dendritic cells in CRS development and exhibit the versatility of this model for therapeutics-induced safety assessment.