bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of esophageal stricture after extensive endoscopic resection: a transcriptomic analysis
Authors: Barret Maximilien , Doridot Ludivine , Le Gall Morgane , Beuvon Frédéric , Jacques Sébastien , Pellat Anna , Belle Arthur , Abou Ali Einas , Dhooge Marion , Leblanc Sarah , Camus Marine , Nicco Carole , Coriat Romain , Chaussade Stanislas , Batteux Frédéric , Prat Frédéric
Published: December 2022

Background and study aims Esophageal stricture is the most frequent adverse event after endoscopic resection for early esophageal neoplasia. Currently available treatments for the prevention of esophageal stricture are poorly effective and associated with major adverse events. Our aim was to identify transcripts specifically overexpressed or repressed in patients who have developed a post-endoscopic esophageal stricture, as potential targets for stricture prevention.

Patients and methods We conducted a prospective single-center study in a tertiary endoscopy center. Patients scheduled for an endoscopic resection and considered at risk of esophageal stricture were offered inclusion in the study. The healthy mucosa and resection bed were biopsied on Days 0, 14, and 90. A transcriptomic analysis by microarray was performed, and the differences in transcriptomic profile compared between patients with and without esophageal strictures.

Results Eight patients, four with esophageal stricture and four without, were analyzed. The mean ± SD circumferential extension of the mucosal defect was 85 ± 11 %. The transcriptomic analysis in the resection bed at day 14 found an activation of the interleukin (IL)-1 group (Z score = 2.159, P = 0.0137), while interferon-gamma (INFγ) and NUPR1 were inhibited (Z score = –2.375, P = 0.0022 and Z score = –2.333, P = 0.00131) in the stricture group. None of the activated or inhibited transcripts were still significantly so in any of the groups on Day 90.

Conclusions Our data suggest that IL-1 inhibition or INFγ supplementation could constitute promising targets for post-endoscopic esophageal stricture prevention.
Utilidad de la ecografía en la cirugía de la mano: Parte II
Authors: Díaz Homid Fahandezh-Saddi , Martínez Manuel Villanueva , Fernández Fernando Dávila , Horcajadas Ángel Bueno , Luna Antonio Ríos , Iborra Álvaro , Yubero María Elena Cantero
Published: December 2022

En los últimos años, con los avances técnicos en la ecografía, aumentó la calidad de las imágenes, lo que ha permitido a los cirujanos mejorar su capacidad de evaluar la mano y la muñeca. Las infiltraciones ecoguiadas en cirugía de mano son más precisas y seguras en comparación con las infiltraciones sin el uso de ecografía. El desarrollo de la técnica de ecografía y de transductores de alta resolución nos ayuda a realizar procedimientos ecoguiados, como el tratamiento del dedo en gatillo, la liberación del síndrome del túnel carpiano, y la aponeurotomía en la enfermedad de Dupuytren. El objetivo de este trabajo es describir las técnicas ecográficas en el tratamiento de las patologías de la mano y el estado del arte de las cirugías ecoguiadas de la mano y sus resultados.
Upper Extremity Deep Venous Thrombosis: Etiologies, Diagnosis, and Updates in Therapeutic Strategies
Authors: Koethe Yilun , Bochnakova Teodora , Kaufman Claire S.
Published: December 2022

Upper extremity deep vein thrombosis (UEDVT) is responsible for 4 to 10% of all deep vein thrombosis (DVT). Untreated UEDVT can lead to significant disability secondary to the postthrombotic syndrome. To date, there are no randomized trials specifically comparing different therapeutic strategies. Ultimately, optimal management of UEDVT depends on the underlying etiology, patient symptoms, and degree of thrombosis, with supporting evidence primarily extrapolated from lower extremity DVT data. This article will review the classification, presentation, and diagnosis of both primary and secondary UEDVT. In addition, it will discuss updates in clinical guidelines, anticoagulation, endovascular and surgical treatment strategies.
Tratamiento de lesiones escafolunares mediante reconstrucción con plastia del extensor radial largo del carpo
Authors: Gutiérrez Miguel del Cerro , Díaz Verónica Jiménez , Lamas Lorena García , Donaire Jorge García , Osorio María Teresa Vázquez
Published: December 2022

Objetivo Describir la técnica quirúrgica de reconstrucción del ligamento escafolunar asistida por artroscopia empleando como donante el extensor carpi radialis longus (ECRL), un músculo que, gracias a sus propiedades biomecánicas, puede ser muy ventajoso en este tipo de cirugía.

Técnica Quirúrgica Tras artroscopia diagnóstica inicial según la técnica habitual, se llevó a cabo la reconstrucción ligamentosa empleando un hemitendón del ECRL mediante técnica mínimamente invasiva. Los dispositivos de fijación empleados fueron el SwiveLock para el escafoides y el tornillo de biotenodesis de 3 × 8 mm (Arthrex, Naples, FL, EE.UU.) para el semilunar.

Complicaciones La complicación que puede surgir durante la realización de esta técnica es la extracción dificultosa de la plastia, por la intersección entre el primer y el segundo compartimentos extensores. Es fácilmente solventable realizando una incisión intermedia a nivel de la intersección para garantizar la adecuada liberación de la plastia a esta altura.

Conclusión Es posible reconstruir el intervalo escafolunar empleando un hemitendón del ECRL, que, por propiedades biomecánicas, puede ser más ventajoso a la hora de restaurar la biomecánica del carpo. Se precisan estudios posteriores para confirmar la idoneidad y la superioridad de este donante frente a otros empleados en las técnicas de reconstrucción.
¿Cómo influyen los trastornos del estado de ánimo en el paciente con Rizartrosis?
Authors: Oteo-Maldonado Jose A. , Merino-Carretero Patricia , Llarena-Barroso Cristina
Published: December 2022

Objetivo La ansiedad y/o depresión juegan un papel fundamental en la forma en la que el paciente afronta la patología osteoarticular. El objetivo de este estudio es describir el impacto de los trastornos del estado de ánimo en la artrosis trapeciometacarpiana (TMC).

Materiales y Métodos Se realizó un estudio descriptivo en pacientes diagnosticados de rizartrosis entre enero de 2018 y enero de 2020. Se recogieron tanto los factores clínicos y demográficos: edad, género, índice de masa corporal (IMC), y diagnóstico de ansiedad y/o depresión; así como los propios de la patología: lateralidad, grado de rizartrosis, fuerza de puño, y fuerza de pinza. También se evaluaron los puntajes en la escala visual analógica de dolor (EVA) y la versión corta del cuestionario de Discapacidades del Brazo, Hombro y Mano (Quick Disabilities of the Arm, Shoulder and Hand – QuickDASH, en inglés).

Resultados Fueron revisados 107 pacientes (85% de mujeres) con edad media de 59,48 ± 7,5 años e IMC medio de 28,29 Kg/m2. El 21,5% de los pacientes estaban diagnosticados de ansiedad y/o depresión, el 51,4% presentaban lateralidad izquierda, y el 48,6%, derecha. Según la Escala de Eaton, el 54.2% de los pacientes eran grado III, y el 45,8%, IV. La fuerza media de puño fue de 15,64 Kg, y la de pinza, de 3,37 Kg. El puntaje medio en la EVA fue de 8,28, y en el QuickDASH, de 65,94.

Se encontró una asociación estadística significativa entre el diagnóstico de ansiedad y/o depresión y el género (p = 0.023), la fuerza de pinza (p = 0,007), y el QuickDASH (p = 0.004). No se vio esta relación estadística con otros parámetros. La significación respecto a la fuerza de pinza desapareció al corregir por género.

Conclusión La presencia de ansiedad y/o depresión en los pacientes con rizartrosis se asocia con el género femenino y con una peor valoración de la funcionalidad por parte del paciente (puntajes altos en el QuickDASH), pero no con el dolor según la EVA. Esto nos indica la importancia de siempre considerar los trastornos del estado de ánimo cuando estudiemos a nuestros pacientes, dada su influencia en la percepción de la patología osteoarticular.
Effect of Different Root Canal Drying Protocols on the Bond Strength of Two Bioceramic Sealers
Authors: Frasquetti Karine Santos , Piasecki Lucila , Kowalczuck Alexandre , Carneiro Everdan , Westphalen Vânia Portela Ditzel , Neto Ulisses Xavier da Silva
Published: December 2022

Objectives This study evaluated in vitro the effect of two different drying protocols on the dentin bond strength of two different bioceramic sealers (Sealer Plus BC [SP] and Bio C Sealer [BCS]). Bond strength and failure mode were evaluated according to the sealer, drying protocol, and root canal third.

Materials and Methods Sixty extracted human mandibular single-rooted premolars were selected after anatomical standardization. The crowns were sectioned and root canals were prepared. Roots were randomly divided into four groups (n = 15 each). Each group was assigned a combination of one of the evaluated sealers (SP or BCS) and one of the drying protocols: canals dried with paper points (PP) or irrigation with saline followed by aspiration with silicon cannulas (IA). Obturations were performed using a single-cone technique. The teeth were temporized and stored for 7 days (100% humidity, 37°C). Roots were cut to obtain 2 mm thick discs for each third (coronal, middle, and apical). Push-out tests were performed on a universal testing machine, and the bond strength (MPa) of each specimen was calculated by dividing the load (N) by the interface area. Failure type was assessed under ×4 magnification.

Statistical Analysis Data were statistically analyzed with a significance set at 5%. An analysis of variance test followed by the Games-Howell post-hoc test was used to compare the mean values between the groups and the interaction of the variables.

Results The predominant failure type was cohesive, followed by mixed failure and adhesive in all groups. The apical third presented the highest bond strength (p < 0.05) regardless of the group, followed by the middle and coronal thirds. Overall, the SP PP group had the highest mean bond strength (p < 0.01), but the SP sealer was negatively affected by the IA drying protocol in the coronal and middle thirds. The BCS presented similar results within the third stage, regardless of the drying protocol.

Conclusions Sealer Plus BC had a higher bond strength than Bio C Sealer, but it was negatively affected by the irrigation-aspiration protocol in the coronal and middle thirds. For the apical third, there was no difference between the groups; thus, a similar bond strength was observed regardless of the drying protocol or sealer.
Removing AI’s sentiment manipulation of personalized news delivery
Authors: Wu Chuhan , Wu Fangzhao , Qi Tao , Zhang Wei-Qiang , Xie Xing , Huang Yongfeng
Published: December 2022

Artificial intelligence (AI) is empowering personalized online news delivery to accommodate people’s information needs and combat information overload. However, AI models learned from user data are inheriting and amplifying some underlying human prejudice such as the sentiment bias of news reading, which may lead to potential negative societal effects and ethical concerns. Here, substantial evidence shows that AI is manipulating the sentiment orientation of news displayed to users by promoting the presence chance of negative news, even if there is no human interference. To mitigate this manipulation, a sentiment-debiasing method based on a decomposed adversarial learning framework is proposed, which can reduce 97.3% of sentiment bias with only 2.9% accuracy sacrifice. Our work provides the potential in improving AI’s responsibility in many human-centered applications such as online journalism and information spread.
Exploring the promoting effect of working time reduction on life satisfaction using Germany as a case study
Authors: Shao Qinglong
Published: December 2022

Worktime reduction’s effect on life satisfaction is an important issue but one that has not been fully studied. This article fills this gap and uses an ordered probit model to analyse the working time reduction impact on life satisfaction in Germany by using the European Social Survey data, the mediating effect of health and cross-partner effect are also explored. A significantly negative correlation between working time and life satisfaction are revealed, showing that a short working week can improve Germans’ life satisfaction. Health is confirmed to be the important intermediate variable in the ‘worktime–health–life satisfaction’ nexus and about 28% of the satisfaction among German people is due to the change in health explained by working hours. Further, we find that high-earners prefer to work long hours whereas low-earners tend to work less; middle-earners show no personal preferences. Cross-partner effects are confirmed, as a male’s short working week can satisfy their partner, while a female’s long working hours can improve their partner’s life satisfaction. In light of this, working hours should be restricted to avoid unsatisfaction induced by overtime work and overtime compensation regulations should be strictly implemented, policy-makers also need to take gender differences into consideration.
A coupled SPH-DEM approach for modeling of free-surface debris flows
Authors: Lin Xiaohui , Li Gang , Xu Fangchen , Zeng Kehong , Xue Jixu , Yang Wenming , Wang Fei
Published: December 2022

A Lagrangian mesh-less model is proposed to simulate fluid–solid flows with multiple-sized solids, i.e., millimeter-sized particle and larger-sized debris. Considering the difference in the size of solid phases, a hybrid resolved and unresolved model is established based on the coupling method of smoothed particle hydrodynamics (SPH) and discrete element method (DEM). SPH is used to model fluid, and the locally averaged Navier–Stokes equations are adopted as governing equations. DEM is used to model the particle–particle interactions, and the unresolved description of hydrodynamic forces including drag and buoyancy is established. The large-sized debris is modeled as the rigid body, which is discretized by particle elements having both SPH and DEM characteristics, where SPH particle elements are involved in the closure of the SPH fluids, and DEM particle elements interact with the solid particles following the contact law. The numerical model is validated and verified by several examples, including single-particle sedimentation, collapse of cylinder columns, and debris dam break. Results show that the present model reproduces general features of the complex fluid–solid flow with free surfaces. The advantage of the hybrid model is that it can deal with the fluid–solid flow problem with both small particles and large objects at a suitable resolution, and it is especially good at dealing with the free surface flow problem. A discretization for the modeling of debris flows is proposed based on the coupled SPH-DEM method. The novelty of the work is a coupled resolved–unresolved scheme for the free surface flow with multi-sized solids. The present scheme allows using a uniform resolution by bridging the size difference between small-scale solid particles and large-scale debris. The unresolved model of fluid-particle flow is efficient because the fluid resolution can be configured comparably to the particle size. The unified nature of the model allows the combination of resolved and unresolved simulations in the same computational domain.
Utilizing bifurcations to separate particles in spiral inertial microfluidics
Authors: Valani Rahil N. , Harding Brendan , Stokes Yvonne M.
Published: December 2022

Particles suspended in fluid flow through a closed duct can focus to specific stable locations in the duct cross section due to hydrodynamic forces arising from the inertia of the disturbed fluid. Such particle focusing is exploited in biomedical and industrial technologies to separate particles by size. In curved ducts, the particle focusing is a result of balance between two dominant forces on the particle: (i) inertial lift arising from small inertia of the fluid and (ii) drag arising from cross-sectional vortices induced by the centrifugal force on the fluid. Bifurcations of particle equilibria take place as the bend radius of the curved duct varies. By using the mathematical model of Harding et al. [J. Fluid Mech. 875, 1–43 (2019)], we illustrate via numerical simulations that these bifurcations can be leveraged in a spiral duct to achieve a large separation between different sized neutrally buoyant particles and identify a separation mechanism, not previously reported, which exploits the transient focusing of smaller particles near saddle points. We demonstrate this for similar sized particles, as well as particles that have a large difference in size, using spiral ducts with a square cross section. The novel formalism of using bifurcations to manipulate particle focusing can be applied more broadly to different geometries in inertial microfluidics, which may open new avenues in particle separation techniques.
Calculating Crime Rates
Authors: Boivin Rémi
Published: December 2022

Dividing the number of crimes in an area at a given time by the population of the same area at the same time has become the standard way to present the criminal phenomenon. Such a crime rate is obviously an appealing indicator: it is easy to calculate and based on readily available data. Consequently, crime rates allow much-wanted comparisons. However, there is growing empirical evidence that these advantages are accompanied by inaccuracies.

There are two main strategies used to control for population (size) when studying crime and three pillars of crime rates: that the level of crime activity is well measured, that the relationship of population to crime is both obvious and trivial, and that residential population size is sufficient to account for the impact of demographics on crime. Presenting crime rates rarely involve in-depth discussions of the dark figure of crime, “ambient” populations or the impact of demography on crime, even if those questions are implied.
Institutional Dis/Continuities in Higher Education Changes During the Soviet and Post-Soviet Periods in Kazakhstan
Authors: Azimbayeva Gulzhan
Published: December 2022

The Union of Soviet Socialist Republics (USSR) higher education system has undergone radical change since the perestroika period—the Gorbachev period (1985–1991). Perestroika means restructuring in Russian. In this period, the institutional context of higher education was fundamentally transformed by the major upheavals of the political and socioeconomic institutions of the USSR. The changes in the USSR higher education had a major impact on the higher education of Kazakhstan—a former Republic of the USSR. Thus, to understand the changes in higher education in Kazakhstan, it is important to locate them in the stages of the collapse of the USSR. It could be argued that the “institutional dis/continuities” theory would allow a careful examination of the educational changes in the postsocialist context. The “institutional dis/continuities” of the perestroika period draw on path-dependency and critical juncture concepts within historical institutionalism theory. Perestroika period can be seen as a critical juncture in the historical development of higher education. Also, the policy choices which were made during the perestroika period could establish further path-dependencies in policy-making.
Animal Personhood in Sustainability Education
Authors: Kopnina Helen
Published: December 2022

Animal personhood research comes from different theoretical directions: animal rights, animal welfare, compassionate conservation, animal rights law, and many related disciplines. The term “personhood” is taken to lie in three main characteristics, including the capacity to act intentionally, the capacity to experience feelings, and the possession of moral worth. This division is complementary to three approaches: the perfectionist approach, the humanistic approach, and the interactive approach, with the third approach being the strongest. The basic idea is that personhood can be linked to legal rights based on recognition of intrinsic rights based on sentience or other characteristics of a living being, including personality. The move toward recognizing animal personhood in education promises to signify a return to a nonanthropocentric ethic that characterizes both the most transformative forms of education for environmental sustainability and the type of education that stresses responsibility and compassion toward all living beings. This type of education, at both the school and university levels, supports both ecocentrism and animal ethics and supports the rights to life of all living beings on Earth—including, to state the obvious, humans. Many initiatives supporting developing education for animal personhood have emerged within the literature on (sustainability) education and practice. This literature emphasizes multiple forms of education, ranging from education for sustainability, education related to ethics (anything that fits under the broad banner of sustainability, from human rights to social justice and indeed animal welfare), for example, including posthumanist education, action research, education for sustainable development, curriculum development, pedagogical studies that specifically engage with animal rights, and animal welfare education. More specifically, Animal Protection Education provides students and teachers with the information they need to understand and discuss the concept of granting legal personhood to animals.
Documentary Genre in Environmental Education
Authors: Ahn Claire
Published: December 2022

Considering the current context—the continued seriousness of environmental issues, the need for environmental education, and the overwhelming amount of and ease of access to media—educators cannot and should not discount the role the media plays in addressing sustainable education. Specifically, as documentary films continue to be a popular choice for audiences to learn about the environment, educators should not just consider the content or the issues addressed, but also consider the nuanced effects of the genre and its patterns, such as the use of images on viewers’ understanding, awareness, and consequently their motivations to act in more eco-conscious ways.
Commerce and Economy in Southeast Asia within the Sinosphere (Laos and Vietnam)
Authors: Anderson James A.
Published: December 2022

Before the 16th century, Southeast Asian trade within the Sinosphere (Laos and Vietnam) took place in a maritime trade network that drew together the Indian Ocean and the South China Sea (Eastern Sea). Land-based and maritime trade routes were interlinked across this region. Behind the maritime trade was the upland supply of forest products that included many of the items most desired by distant markets in China and Southeast Asian destinations. The upland access to trade items was as important as was control of the coastal ports. Westerners arrived in the early modern period, as others had, as traders, and were accommodated into established trading patterns. The general current of anti-imperialism was still to come in the 20th century.
The Japanese Economy Since World War II
Authors: Bytheway Simon
Published: December 2022

Japan’s remarkable postwar experience of economic reconstruction, growth, and development explains much of why it is so intensely studied in other countries today. In common with much of the world and particularly the advanced, capitalist economies of Western Europe, Japan prospered during the years of the long postwar boom (1954–1970). Reestablished by the Truman administration as the archetype of an anti-inflationist, export-based economy, Japan’s success is perhaps unsurprising. What is remarkable, however, is that Japanese economic growth and development continued right up until the 1990s, despite being forced to make abrupt “corrections” to the country’s basic monetary settings by the Nixon and Reagan administrations, changes that precipitated an eventual three-fold increase in the international exchange rate of the yen. Against the backdrop of rising petroleum and energy prices (or “oil shocks”), global inflation, systematic financial crises, widespread economic recession, and the vexing phenomena of stagflation in many of the more mature capitalist economies of the West, the Japanese economy thrived. Japan became the world’s second largest economy (in terms of nominal gross domestic product [GDP]) from 1968 until 2010 with a relatively small population (101 million in 1968 and 128 million in 2010). The fall of Japan’s economic standing from second to third place tragically coincided with the triple disaster of March 11, 2011: an earthquake and tsunami that struck along the Pacific coast of northeastern Japan, causing a nuclear catastrophe. The triple disaster, in turn, led to the fall of the non–Liberal Democratic Party (LDP) Kan and Noda governments, a belated acknowledgement of Japan’s worsening demographic situation (chronic low birthrates with an increasingly elderly population) the re-election of the LDP Abe government, and the return of economic growth ideology in the form of Abenomics and its New Capitalism successor.
Living Standards in Southeast Asia
Authors: Booth Anne
Published: December 2022

The article surveys the evidence on changing living standards across Southeast Asia, a region that in 2020 included a diverse range of countries from Myanmar to the Indonesian and Philippine archipelagos. The region has been described as open and pluralistic, a crossroads of goods, people, and ideas that has never been shut off from the outside world. The years from the mid-15th to the mid-17th centuries have been described by one historian as an age of commerce, where trade and commerce flourished and people from a number of countries in Asia and Europe mingled in port cities. But gradually over the 18th and 19th centuries European powers began to assert their control over much of the region, and by the end of the 19th century the British controlled Burma and Malaya, the French Indochina and the Dutch the huge Indonesian archipelago. In the early 20th century the Americans displaced the Spanish in the Philippines. Population growth in Southeast Asia appears to have been slow between 1600 and 1800, but accelerated over the 19th and 20th centuries compared with other parts of Asia. In the early 19th century population was estimated to be around 10 to 12 percent of that in China, and in 2020 it was almost 48 percent. Evidence of living standards in the early 19th century is examined, as well as how the policies of various colonial powers active in the region in the 19th and early 20th centuries both facilitated population growth and tackled the consequences . Colonial policies tried to increase both food-crop production for domestic consumption and also encouraged export-oriented agriculture, responding to growing global demand for tropical products. These policies often came into conflict as populations increased. By the early 20th century several colonial powers were worried about evidence that living standards were not improving and in some regions were declining. They adopted policies designed to address the problem. After the defeat of Japan, between 1946 and 1965, ten independent countries emerged across Southeast Asia. Governments in all these countries had ambitious plans for improving living standards for their populations, but the extent to which they succeeded in the last half of the 20th century varied considerably. The article examines the evidence, and suggests reasons why some countries have been more successful in improving living standards compared with others.
South–South Cooperation in the 21st Century: An Analysis From Latin America
Authors: Lechini Gladys , Morasso Carla
Published: December 2022

During the first decade of the 21st century, the international system underwent a process of transformation in which emerging actors gained prominence, promoting a new stage that enabled the resurgence of South–South cooperation (SSC). The field of international relations approached this phenomenon mainly through studies of international development cooperation, but also from a foreign policy analysis approach. Although at the beginning of the century attention was focused especially on emerging countries like China, India, Brazil, and South Africa, among others, the consolidation of SSC between middle-income countries, particularly in Latin America, gave rise to a broad debate on the distinct identities of the Southern partners. Considering the substantial literature produced, and emphasizing a perspective rooted in Latin America, SSC is analyzed with the goals of contributing to understand SSC from its conceptual formulation, link SSC to foreign policy considerations, and, finally, understand how SSC has affected the International Development Cooperation System.
Youth Social Exclusion in Latin America
Authors: Saraví Gonzalo A.
Published: December 2022

Globalization and neoliberalism changed the structure and dynamics of contemporary society and imposed a new social question dominated by exclusion, precariousness, and inequality. Social exclusion is not an individual attribute but a social process; it is an inherent result of a neoliberal capitalist society that produces different disposable figures around the world. Exclusion means not “being outside” of society but “being inside” in unfavorable, subordinated, and devalued material, social, and symbolic conditions. Therefore, youth social exclusion implies a process of socialization, subjectivation, and life trajectories in an unfavorable world: a process of inclusion in exclusion. This process crystalizes in at least three main spheres: space, the self, and the life course of young people. In Latin America, extreme social and material deprivation intersects with gender inequality relations, social (mis)recognition, violence and crime, institutional weakness, and growing spaces of (i)legalisms, among other dimensions. All of them shape the place, subjectivity, and biography of most disadvantaged young people throughout the Latin American continent.
Recent advances in cancer fusion transcript detection
Authors: Dorney Ryley , Dhungel Bijay P , Rasko John E J , Hebbard Lionel , Schmitz Ulf
Published: December 2022

Extensive investigation of gene fusions in cancer has led to the discovery of novel biomarkers and therapeutic targets. To date, most studies have neglected chromosomal rearrangement-independent fusion transcripts and complex fusion structures such as double or triple-hop fusions, and fusion-circRNAs. In this review, we untangle fusion-related terminology and propose a classification system involving both gene and transcript fusions. We highlight the importance of RNA-level fusions and how long-read sequencing approaches can improve detection and characterization. Moreover, we discuss novel bioinformatic tools to identify fusions in long-read sequencing data and strategies to experimentally validate and functionally characterize fusion transcripts.
Spectral adjustment for spatial confounding
Authors: Guan Yawen , Page Garritt L , Reich Brian J , Ventrucci Massimo , Yang Shu
Published: December 2022

Adjusting for an unmeasured confounder is generally an intractable problem, but in the spatial setting it may be possible under certain conditions. We derive necessary conditions on the coherence between the exposure and the unmeasured confounder that ensure the effect of exposure is estimable. We specify our model and assumptions in the spectral domain to allow for different degrees of confounding at different spatial resolutions. One assumption that ensures identifiability is that confounding present at global scales dissipates at local scales. We show that this assumption in the spectral domain is equivalent to adjusting for global-scale confounding in the spatial domain by adding a spatially smoothed version of the exposure to the mean of the response variable. Within this general framework, we propose a sequence of confounder adjustment methods that range from parametric adjustments based on the Matérn coherence function to more robust semiparametric methods that use smoothing splines. These ideas are applied to areal and geostatistical data for both simulated and real datasets.
Lower levels of small HDL particles associated with increased infectious disease morbidity and mortality: a population-based cohort study of 30 195 individuals
Authors: Harsløf Mads , Pedersen Kasper M , Afzal Shoaib , Davey Smith George , Nordestgaard Børge G
Published: December 2022

Aims

Low levels of HDL cholesterol have been associated with increased risk of infectious disease morbidity and mortality. Nuclear magnetic resonance (NMR) spectroscopy permits the measurement of HDL particle count and allows further subclassification according to particle size. We tested the hypothesis that low number of different HDL subfractions is associated with increased infectious disease morbidity and mortality.

Methods and results

HDL particle counts were measured using NMR spectroscopy in 30 195 individuals aged 22–99 years from the Copenhagen General Population Study. Using multiple-event Cox regression and cause-specific hazard models, we assessed risk of hospitalizations due to infection and infectious disease-related death, from 2003 through 2018. During follow-up, 9303 individuals had one or more infectious disease events, and 1558 experienced infectious disease-related death. In multifactorial adjusted analyses, low number of small and medium HDL particles was associated with increased risk of any infection and infectious disease-related death, whereas low number of large and extra-large HDL particles was not. A very high number of small and medium HDL particles was also associated with increased risk of any infection, but not with infectious disease-related death. For small and medium HDL particles and compared to individuals in the 91–95th percentile, hazard ratios (HRs) in individuals in the lowest percentile were 2.31 (95% confidence interval: 1.75, 3.05) for any infection and 3.23 (2.08, 5.02) for infectious disease-related death. For the highest percentile, corresponding HRs were 1.36 (1.07, 1.74) and 1.06 (0.57, 1.98), respectively. Individuals in the lowest percentile had increased risk of pneumonia (HR: 1.86; 95% confidence interval: 1.30, 2.65), sepsis (2.17; 1.37, 3.35), urinary tract infection (1.76; 1.17, 2.63), skin infection (1.87; 1.24, 2.81), gastroenteritis (1.78; 1.01, 3.16), and other infections (2.57; 1.28, 5.16).

Conclusion

Low number of the small HDL particles was associated with increased infectious disease morbidity and mortality.
The modular pYT vector series employed for chromosomal gene integration and expression to produce carbazoles and glycolipids in P. putida
Authors: Weihmann Robin , Kubicki Sonja , Bitzenhofer Nora Lisa , Domröse Andreas , Bator Isabel , Kirschen Lisa-Marie , Kofler Franziska , Funk Aileen , Tiso Till , Blank Lars M , Jaeger Karl-Erich , Drepper Thomas , Thies Stephan , Loeschcke Anita
Published: December 2022

The expression of biosynthetic genes in bacterial hosts can enable access to high-value compounds, for which appropriate molecular genetic tools are essential. Therefore, we developed a toolbox of modular vectors, which facilitate chromosomal gene integration and expression in Pseudomonas putida KT2440. To this end, we designed an integrative sequence, allowing customisation regarding the modes of integration (random, at attTn7, or into the 16S rRNA gene), promoters, antibiotic resistance markers as well as fluorescent proteins and enzymes as transcription reporters. We thus established a toolbox of vectors carrying integrative sequences, designated as pYT series, of which we present 27 ready-to-use variants along with a set of strains equipped with unique ‘landing pads’ for directing a pYT interposon into one specific copy of the 16S rRNA gene. We used genes of the well-described violacein biosynthesis as reporter to showcase random Tn5-based chromosomal integration leading to constitutive expression and production of violacein and deoxyviolacein. Deoxyviolacein was likewise produced after gene integration into the 16S rRNA gene of rrn operons. Integration in the attTn7 site was used to characterise the suitability of different inducible promoters and successive strain development for the metabolically challenging production of mono-rhamnolipids. Finally, to establish arcyriaflavin A production in P. putida for the first time, we compared different integration and expression modes, revealing integration at attTn7 and expression with NagR/PnagAa to be most suitable. In summary, the new toolbox can be utilised for the rapid generation of various types of P. putida expression and production strains.
Role of Hypoxia-inducible factor 1α in host defense during pneumococcal pneumonia
Authors: Pereverzeva Liza , Otto Natasja A , Peters-Sengers Hessel , Roelofs Joris J T H , de Vos Alex F , van der Poll Tom
Published: December 2022

Hypoxia-inducible factor (HIF)1α is a transcription factor involved in cellular metabolism and regulation of immune cell effector functions. Here, we studied the role of HIF1α in myeloid cells during pneumonia caused by the major causative pathogen, Streptococcus pneumoniae (Spneu). Mice deficient for HIF1α in myeloid cells (LysMcreHif1αfl/fl) were generated to study the in vitro responsiveness of bone marrow-derived macrophages (BMDMs) and alveolar macrophages (AMs) to the Gram-positive bacterial wall component lipoteichoic acid (LTA) and heat-killed Spneu, and the in vivo host response after infection with Spneu via the airways. Both BMDMs and AMs released more lactate upon stimulation with LTA or Spneu, indicative of enhanced glycolysis; HIF1α-deficiency in these cells was associated with diminished lactate release. In BMDMs, HIF1α-deficiency resulted in reduced secretion of tumor necrosis factor (TNF)α and interleukin (IL)-6 upon activation with Spneu but not LTA, while HIF1α-deficient AMs secreted less TNFα and IL-6 in response to LTA, and TNFα after Spneu stimulation. However, no difference was found in the host response of LysMcreHif1αfl/fl mice after Spneu infection as compared to controls. Similar in vivo findings were obtained in neutrophil (Mrp8creHif1αfl/fl) HIF1α-deficient mice. These data suggest that myeloid HIF1α is dispensable for the host defense during pneumococcal pneumonia.
ACCELERATED BRAIN AGING IS ASSOCIATED WITH MORTALITY ACROSS RACE
Authors: Casanova Ramon , Anderson Andrea , Barnard Ryan , Walker Keenan , Hughes Timothy , Kritchevsky Stephen , Wagenknecht Lynne
Published: December 2022

There is an increasing interest in using machine learning and artificial intelligence to estimate chronological age using neuroimaging data. The gap between chronological age and estimated brain age (brain age gap, BAG) is used as a measure of accelerated/resilient brain aging. Accelerated brain aging has been associated with increased mortality risk. However, these reports are based on cohorts mostly composed by white individuals. Here we capitalized on the racially diverse nature of the Atherosclerosis Risk in Communities Study (ARIC) cohort to investigate associations of brain across race. We used brain MRI scans from 1172 cognitively normal ARIC participants that were collected at ARIC Visit 5. Of those 772 were White and 366 were African Americans. We used Cox regression models to investigate BAG values associations with mortality. There were 163 deaths (dw = 124 and daa = 39) over 8 years of follow-up. Participants were stratified by tertiles according to BAG values. We found that, compared to those individuals with BAG scores in the highest tertile (>=1.15), those who scored in the lowest tertile (<= -1.3 years) to be associated with significantly lower mortality among the White (HR=0.41, 95% CI, [0.26–0.66], p < 0.001) and Black (HR=0.43, 95% CI, [0.20–0.92], p = 0.03) participants after adjusting for age, race-center, sex, education, diabetes, smoking and hypertension. Our analyses show that our approach to estimate chronological age using high-dimensional elastic net regression, produces BAG values which are associated with mortality not only in White individuals but also in African Americans.
A Quantitative Method for the Study of HIV-1 andMycobacterium tuberculosisCoinfection
Authors: Donnellan Samantha , Pennington Shaun H , Ruggiero Alessandra , Martinez-Rodriguez Carmen , Pouget Marion , Thomas Jordan , Ward Steve A , Pollakis Georgios , Biagini Giancarlo A , Paxton William A
Published: December 2022

Mycobacterium tuberculosis and human immunodeficiency virus-1 (HIV-1) syndemic interactions are a major global health concern. Despite the clinical significance of coinfection, our understanding of the cellular pathophysiology and the therapeutic pharmacodynamic impact of coinfection is limited. Here, we use single-round infectious HIV-1 pseudotyped viral particles expressing green fluorescent protein alongside M. tuberculosis expressing mCherry to study pathogenesis and treatment. We report that HIV-1 infection inhibited intracellular replication of M. tuberculosis and demonstrate the therapeutic activity of antiviral treatment (efavirenz) and antimicrobial treatment (rifampicin). The described method could be applied for detailed mechanistic studies to inform the development of novel treatment strategies.
Poverty Reduction through Growth, Redistribution and Social Inclusion in Times of COVID-19: Kenyan Evidence on the Underlying Mechanisms
Authors: Mwabu Germano
Published: December 2022

The paper looks at the nexus between growth, poverty, inequality and redistribution in Africa, using Kenya as a case study. The existing literature shows a strong causal link from growth to poverty reduction. This link is the basis for the pro-poor poverty reduction strategy. There is evidence from the AERC studies that, poverty reduction in a given period is associated with higher growth rates in successive periods that are inequality-reducing and conceptually long lasting. This virtuous spiral of poverty reduction, higher growth and less inequality over time, is the basis for the pro-growth poverty reduction strategy that has recently been emphasized in the literature ( Thorbecke and Ouyang, 2022). The two poverty reduction strategies, a pro-poor strategy and a pro-growth poverty reduction one, complement each other, sustaining household escapes from poverty over time. The paper provides evidence from Kenya showing that human capital formation is the key mechanism underlying the virtuous spiral of lower poverty, higher growth and less inequality as the economy progresses through time. A perspective on robustness of the virtuous spiral in the context of COVID-19 and other pandemics is offered in the concluding section of the paper.
Variations in life cycle and seasonal sex ratio in the rhizocephalan Peltogasterella gracilis (Boschma, 1927) (Cirripedia: Rhizocephala: Peltogasterellidae)
Authors: Kajimoto Asami , Høeg Jens T , Kato Kenji , Yusa Yoichi
Published: December 2022

Most individuals of the rhizocephalan Peltogasterella gracilis (Boschma, 1927) produce only male (larger) or female (smaller) offspring, but some mixed-sex broods appear in autumn. Such variability may be an adaptation to the seasonally changing availability of hosts (for female larvae) and conspecific females (for male larvae), but details of the seasonal variation in the sex ratio and its ultimate causes have not been fully studied in P. gracilis. We studied the life cycle, host availability, and seasonal sex-ratio variation in P. gracilis by samplings from spring to autumn in 2017–2020 in Otaru, and additionally from winter to spring of 2007 in Oshoro Bay, Hokkaido, northern Japan. We measured its prevalence on the hermit crab Pagurus lanuginosus De Haan, 1849, the number of males per externa, the proportion of externae brooding different embryonic stages, and embryo size that are linked to sex. The prevalence was about 20% in most of the sampling period. The number of males per externa was 0.01–0.74 in June 2018–2020, but increased in later months to nearly 1.0. Eyed embryos and nauplii before hatching were common from June or July to September, but they were rare in other seasons. Female embryos were observed in all sampling periods, but male embryos were not found in July or August, by which time most females already have males implanted within their receptacles. It is suggested that P. gracilis releases both female and male larvae according to the availability of unparasitized hosts and of virgin externae, respectively.
scRNA-seq profiling of neonatal and adult thymus-derived CD4+ T cells by a T cell origin-time tracing model
Authors: Han Yuheng , Ouyang Xinxing , Chen Yao , Lai Shujing , Sun Hongxiang , Wu Ningbo , Ruan Chun , Lu Limin , Su Bing
Published: December 2022

It is well documented that the neonatal thymus-derived (neonatal-TD) regulatory T cells (Treg) are essential to prevent lethal autoimmune diseases and allergies, and neonatal and adult thymus possesses distinct output potentials for naïve T cells, including Treg. However, the molecular features and detailed functional differences between neonatal-TD and adult thymus-derived (adult-TD) T cells in terms of their ability to maintain immune homeostasis during long-term environmental influences are still largely unknown, partially due to the lack of appropriate animal models to precisely trace these cells at specific time points. In this study, neonatal-TD and adult-TD CD4+ T cells from the spleen and Peyer's patches were traced for 9 weeks by a T cell origin-time tracing mouse model and analysed by single-cell RNA sequencing. More Treg but fewer naïve T cells were found in neonatal-TD CD4+ T cells from both tissues than those from adult-TD counterparts. Interestingly, the neonatal-TD Treg in both the spleen and Peyer's patches exhibited augmented expression of Foxp3, Gata3, Ctla4, Icos, Il2ra, Tgfb1, and Nrp1, as well as enriched Gene Ontology terms like T cell activation and tolerance induction, indicating an enhanced immunosuppressive function. These results were further confirmed by flow cytometry analysis and in vitro immune suppression assays. Flow cytometry also revealed a significantly higher proportion of neonatal-TD Treg in total Treg than that of adult-TD counterparts, suggesting the longer lifespan of neonatal-TD Treg. To investigate the intrinsic features of neonatal-TD and adult-TD CD4+ T cells, a shortened tracing time was performed. Surprisingly, the neonatal-TD and adult-TD CD4+ T cells had similar proportions of Treg and did not exhibit significant differences in Foxp3, Gata3, Ctla4, Icos, Il2ra, and Tgfb1 expression levels after tracing for 12 days. On the other hand, neonatal-TD Treg present an increased Nrp1 expression level compared with adult-TD counterparts, indicating the enhanced stability. Together, our work reveals that the neonatal-TD Treg are more immunosuppressive, which is likely shaped primarily by environmental factors.