bluuebunny/crossref_metadata_2025 huggingface dataset:
The Anti-Racism Behavioral Inventory: A Validation Study
Authors: Pieterse Alex L. , Kirkinis Katherine , Paiko Lynsay , Miller Matthew
Published: February 2023

The current study extends the initial creation and validation of the Anti-Racism Behavioral Inventory (ARBI; Pieterse, Utsey & Miller, 2016), a measure designed to assess anti-racism awareness and behavior among Whites Americans. Given that the original measure was developed with a sample of graduate students in counseling psychology, the current study extends validation to a sample of White individuals who identify as anti-racism activists (N=153).  Findings support the original bifactor factor model of the Anti-Racism Behavioral inventory (one general anti-racism behavior factor and three domain-specific factors: individual advocacy, awareness of racism, and institutional advocacy). Additional evidence for validity was supported through negative associations with measures of the color-blind racial attitudes, as well as positive associations with scores on the White Privilege Awareness Inventory. Implications of the findings for training and future research are discussed.
Gamla Uppsala – the emergence of a centre and a magnate complex
Authors: Ljungkvist John , Frölund Per
Published: February 2023

The emergence of Gamla Uppsala as a centre has been discussed for centuries. During the past years, old excavations have been incorporated into the frame-work of the archaeological research project Gamla Uppsala - the emergence of a mythical centre (GUAM), with GIS and excavations in combination with survey results and reinterpretations, as old excavations are placed in relation to new investigations. This article is based on the results from excavations in 2011 and 2015 and studies of previous investigations in the light of new results. We have chosen to present a stand der forschung of what we currently know about the 6th to 8th century estate in the centre of Gamla Uppsala, how it emerges as part of an unparalleled monumentalization of the area, what we know of a Migration Period prelude and its transformation during the 8th/9th century. Today we can discuss the relationship between a multitude of elements in the complex, such as individual mounds, the great hall, workshops, economy buildings, fences, paved courtyards, post-row monuments and not least landscape development and resource exploitation on a broad scale. In our strategic work, previously isolated monuments are tied together in a project that will continue in the years ahead.
Small Masks on Migration Period jewellery.
Authors: László Tóth Bálint
Published: February 2023

The three Swedish gold collars are unique goldsmith masterpieces of the Migration Age, owing to the great number of small beings that inhabit them: animals, humans and hybrids. While most of these figurines were individually carved into the gold and ornated with filigree or granulation, the small masks of the Ålleberg collar stand out as seemingly being replicates. Which method was used to replicate these originally 43 masks on the collar? A thorough study of these masks is presented as well as of the bracteates decorated with replicated or unique masks. Two different techniques are proposed for the manufacture of these small masks, both going back to Roman goldsmith techniques. One of these techniques was widely used in the antique and Germanic worlds and it has its roots in Greek methods of the Archaic period. The technique used to make the masks on the Ålleberg collar and on a few of the bracteates is of a much rarer type, which only has parallels in Roman goldsmith techniques of the 2nd – 4th A.D.
El localisme en les polítiques contra el sensellarisme
Authors: Sales Campos Albert
Published: February 2023

Les polítiques públiques que aborden el sensellarisme a les grans ciutat europees s’han centrat en atendre a les persones sense sostre oferint allotjament temporal i acompanyament social. Les actuacions de les administracions i de les entitats socials es dissenyen i gestionen des de l’àmbit local. Les perspectives assistencialista i localista són conseqüència de la construcció d’un objecte d’estudi i d’intervenció social, la persona sense llar, desvinculat dels factors d’exclusió social i residencial que afecten al conjunt de la població. Dades d’estudis recents realitzats a Barcelona mostren la gran permeabilitat entre les situacions d’exclusió residencial descrites per les categories ETHOS, l’increment de la mobilitat transnacional i metropolitana de les persones excloses de l’habitatge i les dinàmiques supramunicipals de les seves estratègies de supervivència. Aquestes dades conviden a superar el localisme en la definició de la problemàtica i generar una agenda de recerca orientada a la prevenció.
Editorial
Authors: Guijarro Laura
Published: February 2023

Introducció al monogràfic de sensellarisme a càrrec de la seva coordinadora.
EXAMINING THE PHYSICS CONCEPTIONS, SCIENCE ENGAGEMENT AND MISCONCEPTIONS OF UNDERGRADUATE STUDENTS IN STEM
Authors: Bahtaji Michael Allan A.
Published: February 2023

Exploring students’ physics conceptions, science engagement and misconceptions in physics together with their association to certain variables (gender, educational background, and program of study) are essential in improving physics teaching and learning. However, few studies have been conducted to explore these three measures and almost none among STEM undergraduate students in the domain of Newtonian mechanics. To explore these measures, the Force Concept Inventory (FCI) and the Science Engagement Survey (SES) were administered to 281 STEM undergraduate students. Various statistical tools (ANOVA, t-test, correlations, etc.) have been utilized in the data analyses. The result revealed that gender and previous upper-secondary school strand have no significant effect on physics conceptions but have a significant effect on science engagement. The results also revealed a weak correlation between physics conceptions and science engagement, suggesting that interest becomes more effective when it was developed during the learning process. Finally, the results also revealed that more than 80% of the participants have a misunderstanding about the force direction of a thrown object, confirming that the dominant features of force and motion students have less conform to problems that involve non-contact force.
Keywords: conceptual change, misconceptions, physics conceptions, science engagement.
EXAMINING THE TYPE AND QUALITY OF QUESTIONS ASKED BY A SCIENCE TEACHER
Authors: Saka Tolga , Inaltekin Tufan
Published: February 2023

Exploring science teachers' classroom assessment behaviors is a way to understand the professional knowledge competencies underlying effective teaching practices. One of the most important components of in-class assessments is teacher questions. However, studies examining teacher questions that provide support to accurately determine student learning and manage the lesson effectively are quite limited. This research presents a case study of a science teacher in Turkey regarding the question types and questioning proficiency in the teaching of 5th grade "Measurement of Force and Friction" and "Matter and Change". The data have been collected through course observations. The study used an observation evaluation protocol to analyze the video recordings taken from the science teacher's lectures. The results of this study showed that about half of the questions that the science teacher has asked in his class remain at a partially appropriate and inappropriate level, and that the teacher mostly prefers questions that aim to evaluate real information and summarize what is important in his courses. These results point to the need for professional development on a teacher's questioning practices. Therefore, it can be said that those who plan professional development programs for science teachers should consider efforts to improve teacher questioning practices. Keywords: case study, classroom observation, science questions, science teacher questioning
Diseño y validación de instrumento para la internacionalización de pymes, a partir del modelo Uppsala y las capacidades dinámicas
Authors: Rave-Gómez Elkin Darío , Moreno Hernandez Joan Esteban , Pérez Castañeda Suly Sendy
Published: February 2023

Las pymes han sido determinantes en la actividad económica colombiana por su contribución en la generación de empleos y el impacto positivo sobre la producción. Por lo tanto, esta investigación tuvo como objetivo establecer las categorías y variables clave que inciden en la internacionalización de las pymes, partiendo del modelo Uppsala y la teoría de las capacidades dinámicas. La metodología que se aplicó fue el modelo de ecuaciones estructurales. Se trabajó con una muestra de 100 pymes pertenecientes al sector textil-confección, localizadas geográficamente en el Valle de Aburrá, en los alrededores de la ciudad de Medellín, Colombia. Para definir las relaciones teóricas, entre categorías, variables y las hipótesis, se creó el diagrama de sendero como estrategia para observar de mejor manera las relaciones causales entre variables dependientes e independientes. El análisis de los datos para la confiabilidad del instrumento se realizó con SPSS, para posteriormente correr las ecuaciones estructurales en el software LISREL. El alcance de los resultados llegó hasta elegir qué categorías y variables del modelo Uppsala y las capacidades dinámicas, eran las adecuadas para incluir en el modelo multivariante y determinar cuáles son las que mayor incidencia tienen en el proceso de internacionalización de una pyme. A manera de conclusión, los hallazgos principales arrojaron que las categorías, Información (siete variables), los Recursos (ocho variables), las Capacidades Dinámicas (ocho variables), son las que más impacto pueden llegar a tener en el proceso de internacionalización de las pymes.
AN IRONIC INTERSECTION OF REALITY AND FICTIONALITY: TLÖN, UQBAR, ORBIS TERTIUS
Authors: ÖREN Aytaç
Published: February 2023

The irony of reality and fictionality in Tlön, Uqbar, Orbis Tertius by Jorge Luis Borges makes us rethink about exactly what both reality and fictionality/unreality are, and also surprises the reader with the common aspects of the construction processes of reality and fictionality. Fictionality takes the place of reality and this is carried out surprisingly by means of an encyclopedia accepted as the information source for reality. While making an irony of reality and fictionality in the text, Borges follows an encyclopedic style of language and sometimes goes on writing his narration like an article including many footnotes and references; that is, he uses the presentation form of reality by disrupting reality and gives the fictionality the reality appearance in the same presentation way. Tlön is a narrative in which a parallel concept of reality and its gradual, inevitable encroachment dominate every aspect of everyday reality where alternative universe is seen to prevail. In an environment like that where reality loses, what is said in the name of reality becomes doubtful and the question of how real they are preoccupies one’s mind. In this context, this article aims to show how the irony of reality and fictionality is created in the story, ironically draw our attention to what consists of the base of reality and to reveal how the assumptions of reality and fictionality are unsettled.
Recent Developments in Regorafenib Treatment for Gastrointestinal Cancers: Presentations at the Meeting of the European Society for Medical Oncology (ESMO) Congress 2016
Authors: Archbold Julia
Published: February 2023

The European Society for Medical Oncology (ESMO) Congress was held in Copenhagen, Denmark from 7th–11th October 2016. The use of the promiscuous multikinase inhibitor regorafenib (Stivarga®, BAY 73-4506) in the treatment of cancers of the gastrointestinal (GI) tract was strongly featured at this meeting. Regorafenib targets multiple kinases involved in oncogenesis and angiogenesis, and is US Food and Drug Administration (FDA)-approved for the treatment of advanced metastatic colorectal cancer and GI stromal tumours, following progression on standard therapies. In this review, we summarise the results of completed clinical trials on the use of regorafenib alone or in combination with other therapies for the treatment of GI cancers. We highlight the results of the Phase III RESORCE study which demonstrated the efficacy of regorafenib as a second-line therapy in patients with advanced hepatocellular carcinoma who have progressed on sorafenib. We review some promising preliminary data on the use of regorafenib in other GI cancers, such as gastric cancer, oesophageal cancer, pancreatic cancer, and soft tissue carcinomas, and provide a brief overview of ongoing and planned trials. Finally, we discuss the incidence and management of regorafenib-related toxicities and summarise attempts to identify predictive biomarkers of regorafenib sensitivity.
Lärare behöver ge eleverna stöd att tolka representationer i kemiklassrummet
Authors: Schönborn Konrad , Höst Gunnar
Published: February 2023

I en doktorsavhandling utforskar Emelie Patron lärares användning och elevers erfarenheter av visuella representationer av kemisk bindning på gymnasiet. Hon fann bland annat att lärare arbetar med visuella representationer på fem olika sätt, för att hjälpa eleverna att fokusera på viktiga delar av det som visas. En slutsats är att lärare behöver stöd för användning av visuella representationer i kemiklassrummet.
Multidisciplinary approaches to identifying and managing global airways disease: Expert recommendations based on qualitative discussions
Authors: Backer Vibeke , Cardell Lars Olaf , Lehtimäki Lauri , Toppila-Salmi Sanna , Bjermer Leif , Reitsma Sietze , Hellings Peter W. , Weinfeld Dan , Aanæs Kasper , Ulrik Charlotte Suppli , Braunstahl Gert-Jan , Aarli Bernt Bøgvald , Danielsen Arild , Kankaanranta Hannu , Steinsvåg Sverre , Bachert Claus
Published: February 2023

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma frequently co-exist and share pathologic features. Taking a “global” treatment approach benefits diagnosis and treatment of both, but care is often siloed by specialty: joined-up clinics are uncommon. Our objectives were to explore expert opinion to give practical suggestions to identify adults needing global airways care; enhance cross-specialty working; and widen knowledge to support diagnosis and management, integrate with existing care pathways, and supplement existing guidelines.

Methods

Sixteen practicing physicians from northern Europe were invited for their national and/or international standing in treating asthma and/or chronic rhinosinusitis. Appreciative Inquiry techniques were used to guide their discussions.

Results

Key themes arising were screening and referral, collaboration on management, awareness and education, and research. Provided are screening criteria and suggestions for specialist referrals, and pointers for physicians to optimize their knowledge of global airways disease. Collaborative working is underscored, and practical suggestions are given for multidisciplinary teamworking within global airways clinics. Research gaps are identified.

Conclusion

This initiative provides practical suggestions for optimizing the care of adults with CRSwNP and asthma. Discussion of the role of allergy and drug exacerbations on these conditions, and care for patients with other global airways diseases were beyond scope; however, we expect some principles of our discussion will likely benefit patients with related conditions. The suggestions bridge asthma and CRSwNP management guidelines, envisioning interdisciplinary, global airway clinics relevant to various clinical settings. They highlight the value of joint screening for early recognition and referral of patients.
A mathematical and exploratory data analysis of malaria disease transmission through blood transfusion
Authors: Adeniyi Michael O. , Aderele Oluwaseun R. , Oludoun Olajumoke Y. , Ekum Matthew I. , Matadi Maba B. , Oke Segun I. , Ntiamoah Daniel
Published: February 2023

Malaria is a mosquito-borne disease spread by an infected vector (infected female Anopheles mosquito) or through transfusion of plasmodium-infected blood to susceptible individuals. The disease burden has resulted in high global mortality, particularly among children under the age of five. Many intervention responses have been implemented to control malaria disease transmission, including blood screening, Long-Lasting Insecticide Bed Nets (LLIN), treatment with an anti-malaria drug, spraying chemicals/pesticides on mosquito breeding sites, and indoor residual spray, among others. As a result, the SIR (Susceptible—Infected—Recovered) model was developed to study the impact of various malaria control and mitigation strategies. The associated basic reproduction number and stability theory is used to investigate the stability analysis of the model equilibrium points. By constructing an appropriate Lyapunov function, the global stability of the malaria-free equilibrium is investigated. By determining the direction of bifurcation, the implicit function theorem is used to investigate the stability of the model endemic equilibrium. The model is fitted to malaria data from Benue State, Nigeria, using R and MATLAB. Estimates of parameters were made. Following that, an optimal control model is developed and analyzed using Pontryaging's Maximum Principle. The malaria-free equilibrium point is locally and globally stable if the basic reproduction number (R0) and the blood transfusion reproduction number (Rα) are both less or equal to unity. The study of the sensitive parameters of the model revealed that the transmission rate of malaria from mosquito-to-human (βmh), transmission rate from humans-to-mosquito (βhm), blood transfusion reproduction number (Rα) and recruitment rate of mosquitoes (bm) are all sensitive parameters capable of increasing the basic reproduction number (R0) thereby increasing the risk in spreading malaria disease. The result of the optimal control shows that five possible controls are effective in reducing the transmission of malaria. The study recommended the combination of five controls, followed by the combination of four and three controls is effective in mitigating malaria transmission. The result of the optimal simulation also revealed that for communities or areas where resources are scarce, the combination of Long Lasting Insecticide Treated Bednets (u2), Treatment (u3), and Indoor insecticide spray (u5) is recommended. Numerical simulations are performed to validate the model's analytical results.
Extracellular vesicles secreted by human gingival mesenchymal stem cells promote bone regeneration in rat femoral bone defects
Authors: Wang Situo , Liu Ziwei , Yang Shuo , Huo Na , Qiao Bo , Zhang Tong , Xu Juan , Shi Quan
Published: February 2023

Extracellular vesicles (EVs), important components of paracrine secretion, are involved in various pathological and physiological processes of the body. In this study, we researched the benefits of EVs secreted by human gingival mesenchymal stem cells (hGMSC-derived EVs) in promoting bone regeneration, thereby providing new ideas for EVs-based bone regeneration therapy. Here, we successfully demonstrated that hGMSC-derived EVs could enhance the osteogenic ability of rat bone marrow mesenchymal stem cells and the angiogenic capability of human umbilical vein endothelial cells. Then, femoral defect rat models were created and treated with phosphate-buffered saline, nanohydroxyapatite/collagen (nHAC), a grouping of nHAC/hGMSCs, and a grouping of nHAC/EVs. The results of our study indicated that the combination of hGMSC-derived EVs and nHAC materials could significantly promote new bone formation and neovascularization with a similar effect to that of the nHAC/hGMSCs group. Our outcomes provide new messages on the role of hGMSC-derived EVs in tissue engineering, which exhibit great potential in bone regeneration treatment.
Exploring Class I polyhydroxyalkanoate synthases with broad substrate specificity for polymerization of structurally diverse monomer units
Authors: Sivashankari Ramamoorthi M , Mierzati Maierwufu , Miyahara Yuki , Mizuno Shoji , Nomura Christopher T. , Taguchi Seiichi , Abe Hideki , Tsuge Takeharu
Published: February 2023

Polyhydroxyalkanoate (PHA) synthases (PhaCs) are key enzymes in PHA polymerization. PhaCs with broad substrate specificity are attractive for synthesizing structurally diverse PHAs. In the PHA family, 3-hydroxybutyrate (3HB)-based copolymers are industrially produced using Class I PhaCs and can be used as practical biodegradable thermoplastics. However, Class I PhaCs with broad substrate specificities are scarce, prompting our search for novel PhaCs. In this study, four new PhaCs from the bacteria Ferrimonas marina, Plesiomonas shigelloides, Shewanella pealeana, and Vibrio metschnikovii were selected via a homology search against the GenBank database, using the amino acid sequence of Aeromonas caviae PHA synthase (PhaCAc), a Class I enzyme with a wide range of substrate specificities, as a template. The four PhaCs were characterized in terms of their polymerization ability and substrate specificity, using Escherichia coli as a host for PHA production. All the new PhaCs were able to synthesize P(3HB) in E. coli with a high molecular weight, surpassing PhaCAc. The substrate specificity of PhaCs was evaluated by synthesizing 3HB-based copolymers with 3-hydroxyhexanoate, 3-hydroxy-4-methylvalerate, 3-hydroxy-2-methylbutyrate, and 3-hydroxypivalate monomers. Interestingly, PhaC from P. shigelloides (PhaCPs) exhibited relatively broad substrate specificity. PhaCPs was further engineered through site-directed mutagenesis, and the variant resulted in an enzyme with improved polymerization ability and substrate specificity.
New insights into fibrotic signaling in renal cell carcinoma
Authors: Chen Jiao-Yi , Yiu Wai-Han , Tang Patrick Ming-Kuen , Tang Sydney Chi-Wai
Published: February 2023

Fibrotic signaling plays a pivotal role in the development and progression of solid cancers including renal cell carcinoma (RCC). Intratumoral fibrosis (ITF) and pseudo-capsule (PC) fibrosis are significantly correlated to the disease progression of renal cell carcinoma. Targeting classic fibrotic signaling processes such as TGF-β signaling and epithelial-to-mesenchymal transition (EMT) shows promising antitumor effects both preclinically and clinically. Therefore, a better understanding of the pathogenic mechanisms of fibrotic signaling in renal cell carcinoma at molecular resolution can facilitate the development of precision therapies against solid cancers. In this review, we systematically summarized the latest updates on fibrotic signaling, from clinical correlation and molecular mechanisms to its therapeutic strategies for renal cell carcinoma. Importantly, we examined the reported fibrotic signaling on the human renal cell carcinoma dataset at the transcriptome level with single-cell resolution to assess its translational potential in the clinic.
Two new species of Haploporus (Polyporales, Basidiomycota) from China and Ecuador based on morphology and phylogeny
Authors: Man Xiao-Wu , Dai Yu-Cheng , Bian Lu-Sen , Zhou Meng , Zhao Heng , Vlasák Josef
Published: February 2023

At present, 25 species are accepted in Haploporus and are distributed in Asia, Europe, North America, South America, Australia, and Africa. In this study, two new species, Haploporus ecuadorensis from Ecuador and H. monomitica from China, are described and illustrated based on morphological examination and phylogenetic analyses. H. ecuadorensis is characterized by annual, resupinate basidiomata with pinkish buff to honey yellow hymenophore when dry, round to angular pores of 2–4 per mm, a dimitic hyphal structure with generative hyphae bearing clamp connections, hyphae at dissepiment edge usually with one or two simple septa, the presence of dendrohyphidia and cystidioles, and oblong to ellipsoid basidiospores measuring 14.9–17.9 × 6.9–8.8 µm. Haploporus monomitica differs from other Haploporus species in that it has a monomitic hyphal system and strongly dextrinoid basidiospores. The differences between the new species and morphologically similar and phylogenetically related species are discussed. In addition, an updated key to 27 species of Haploporus is provided.
Chimeric antigen receptor-T cell therapy-related cardiotoxicity in adults and children cancer patients: A clinical appraisal
Authors: Camilli Massimiliano , Maggio Luca , Tinti Lorenzo , Lamendola Priscilla , Lanza Gaetano Antonio , Crea Filippo , Lombardo Antonella
Published: February 2023

Chimeric antigen receptor-T (CAR-T) cells therapies represent an innovative immunological treatment for patients suffering from advanced and refractory onco-hematological malignancies. The infusion of engineered T-cells, exposing chimeric receptors on the cell surface, leads to an immune response against the tumor cells. However, data from clinical trials and observational studies showed the occurrence of a constellation of adverse events related to CAR-T cells infusion, ranging from mild effects to life-threatening organ-specific complications. In particular, CAR-T cell-related cardiovascular toxicities represent an emerging group of adverse events observed in these patients, correlated with increased morbidity and mortality. Mechanisms involved are still under investigation, although the aberrant inflammatory activation observed in cytokine release syndrome (CRS) seems to play a pivotal role. The most frequently reported cardiac events, observed both in adults and in the pediatric population, are represented by hypotension, arrhythmias and left ventricular systolic dysfunction, sometimes associated with overt heart failure. Therefore, there is an increasing need to understand the pathophysiological basis of cardiotoxicity and risk factors related to its development, in order to identify most vulnerable patients requiring a close cardiological monitoring and long-term follow-up. This review aims at highlighting CAR-T cell-related cardiovascular complications and clarifying the pathogenetic mechanisms coming at play. Moreover, we will shed light on surveillance strategies and cardiotoxicity management protocols, as well as on future research perspectives in this expanding field.
Annual patterns of stratification, mixing and ventilation in long, deep, seasonally ice-covered François lake, British Columbia, Canada
Authors: Vagle Svein , Carmack Eddy
Published: February 2023

François Lake is a long, deep, seasonally ice-covered, dimictic lake set in an east-west orientation in mid-British Columbia. As a baseline we here present data from a full-depth temperature mooring deployed at the lake’s mid-point in 2004–2005 and one full-depth conductivity-temperature-depth cast. We use these temperature records to define lake stability, scales of motion and the annual cycle of thermal stratification, mixing and deep-water ventilation. Owing to its length (110 km) both the Wedderburn and Lake numbers—indices of thermocline tilt and mixing under wind forcing—transition through critical values during fall and spring seasons, suggesting thermocline outcropping and strong turbulent mixing within the thermocline at these times. Owing to its depth (240 m) the decreasing temperature of maximum density (TMD) with depth (thermobaric effect) adds complexity to overturn events. Owing to its seasonal ice cover (2–3 months per year) the critical period for effective fall ventilation occurs before ice formation and concurrent wind shielding, while that of spring ventilation lies between the dates that the ice cover melts and the lake surface water warms above 4°C. While the lake undergoes full depth ventilation in both fall and spring, we show that both progress in distinct dynamical stages. Fall ventilation is more efficient than that of spring, and the transition temperature and resulting bottom temperature from fall to winter stratification (positive to inverse) and winter to spring stratification (inverse to positive) lies close to the temperature of maximum density calculated for the maximum depth of free and forced convection (in this case, closer to 3.7°C).
Proof-of-concept of feasibility of human–machine peer learning for German noun vocabulary learning
Authors: Hromada Daniel D. , Kim Hyungjoong
Published: February 2023

The present study provides the first empiric evidence that the creation of human–machine peer learning (HMPL) couples can lead to an increase in the level of mastery of different competences in both humans and machines alike. The feasibility of the HMPL approach is demonstrated by means of Curriculum 1 whereby the human learner H gradually acquires a vocabulary of foreign language, while the artificial learner fine-tunes its ability to understand H's speech. The present study evaluated the feasibility of the HMPL approach in a proof-of-concept experiment that is composed of a pre-learn assessment, a mutual learning phase, and post-learn assessment components. Pre-learn assessment allowed us to estimate prior knowledge of foreign language learners by asking them to name visual cues corresponding to one among 100 German nouns. In a subsequent mutual learning phase, learners are asked to repeat the audio recording containing the label of a simultaneously presented word with the visual cue. After the mutual learning phase is over, the subjacent speech-to-text (STT) neural network fine-tunes its parameters and adapts itself to peculiar properties of H's voice. Finally, the exercise is terminated by the post-learn assessment phase. In both assessment phases, the number of mismatches between the expected answer and the answer provided by human and recognized by machine provides the metrics of the main evaluation. In the case of all six learners who participated in the proof-of-concept experiment, we observed an increase in the amount of matches between expected and predicted labels, which was caused both by an increase in human learner's vocabulary as well as by an increase in the recognition accuracy of machine's speech-to-text model. Therefore, the present study considers it reasonable to postulate that curricula could be drafted and deployed for different domains of expertise, whereby humans learn from AIs at the same time as AIs learn from humans.
Expression of NFIL3 and CEBPA regulated by IFNT induced-PGE2 in bovine endometrial stromal cells during the pre-implantation period
Authors: Bai Rulan , Kusama Kazuya , Matsuno Yuta , Bai Hanako , Sakurai ﻿Toshihiro , Kimura Koji , Imakawa Kazuhiko
Published: February 2023

Prostaglandin E2 (PGE2) is considered as a luteoprotective factor, influencing the corpus luteum during the early pregnant period in the bovine species. Cyclic AMP (cAMP) is activated in response to PGE2 and plays a role in many physiological processes. The maternal recognition signal, interferon τ (IFNT), induces PGE2 secretion from the endometrial epithelial cells, the function of which in stroma cells has not been completely understood. In this study, PGE2 was found to activate cAMP in the bovine endometrial stromal cells (STRs). STRs were then treated with forskolin to activate the cAMP signaling, from which RNA extracted was subjected to global expression analysis. Transcripts related to transcription regulatory region nucleic acid binding of molecular function, nucleus of cellular component, and mitotic spindle organization of biological processes were up-regulated in cAMP-activated bovine STRs. An increase in the transcription factors, NFIL3, CEBPA, and HIF1A via the cAMP/PKA/CREB signaling pathway in the bovine STRs was also found by qPCR. Knockdown of NFIL3, CEBPA, or HIF1A blocked forskolin-induced PTGS1/2 and IGFBP1/3 expression. Moreover, NFIL3 and CEBPA were localized in endometrial stroma on pregnant day 17 (day 0 = estrous cycle), but not on cyclic day 17. These observations indicated that uterine PGE2 induced by conceptus IFNT is involved in the early pregnancy-related gene expression in endometrial stromal cells, which could facilitate pregnancy establishment in the bovine.
Serotonin and the ventilatory effects of etonogestrel, a gonane progestin, in a murine model of congenital central hypoventilation syndrome
Authors: Casciato Alexis , Bianchi Lola , Reverdy Manon , Joubert Fanny , Delucenay-Clarke Roman , Parrot Sandrine , Ramanantsoa Nélina , Sizun Eléonore , Matrot Boris , Straus Christian , Similowski Thomas , Cayetanot Florence , Bodineau Laurence
Published: February 2023

Introduction

Congenital Central Hypoventilation Syndrome, a rare disease caused by PHOX2B mutation, is associated with absent or blunted CO2/H+ chemosensitivity due to the dysfunction of PHOX2B neurons of the retrotrapezoid nucleus. No pharmacological treatment is available. Clinical observations have reported non-systematic CO2/H+ chemosensitivity recovery under desogestrel.

Methods

Here, we used a preclinical model of Congenital Central Hypoventilation Syndrome, the retrotrapezoid nucleus conditional Phox2b mutant mouse, to investigate whether etonogestrel, the active metabolite of desogestrel, led to a restoration of chemosensitivity by acting on serotonin neurons known to be sensitive to etonogestrel, or retrotrapezoid nucleus PHOX2B residual cells that persist despite the mutation. The influence of etonogestrel on respiratory variables under hypercapnia was investigated using whole-body plethysmographic recording. The effect of etonogestrel, alone or combined with serotonin drugs, on the respiratory rhythm of medullary-spinal cord preparations from Phox2b mutants and wildtype mice was analyzed under metabolic acidosis. c-FOS, serotonin and PHOX2B were immunodetected. Serotonin metabolic pathways were characterized in the medulla oblongata by ultra-high-performance liquid chromatography.

Results

We observed etonogestrel restored chemosensitivity in Phox2b mutants in a non-systematic way. Histological differences between Phox2b mutants with restored chemosensitivity and Phox2b mutant without restored chemosensitivity indicated greater activation of serotonin neurons of the raphe obscurus nucleus but no effect on retrotrapezoid nucleus PHOX2B residual cells. Finally, the increase in serotonergic signaling by the fluoxetine application modulated the respiratory effect of etonogestrel differently between Phox2b mutant mice and their WT littermates or WT OF1 mice, a result which parallels with differences in the functional state of serotonergic metabolic pathways between these different mice.

Discussion

Our work thus highlights that serotonin systems were critically important for the occurrence of an etonogestrel-restoration, an element to consider in potential therapeutic intervention in Congenital Central Hypoventilation Syndrome patients.
Evaluation of AlphaFold structure-based protein stability prediction on missense variations in cancer
Authors: Keskin Karakoyun Hilal , Yüksel Şirin K. , Amanoglu Ilayda , Naserikhojasteh Lara , Yeşilyurt Ahmet , Yakıcıer Cengiz , Timuçin Emel , Akyerli Cemaliye B.
Published: February 2023

Identifying pathogenic missense variants in hereditary cancer is critical to the efforts of patient surveillance and risk-reduction strategies. For this purpose, many different gene panels consisting of different number and/or set of genes are available and we are particularly interested in a panel of 26 genes with a varying degree of hereditary cancer risk consisting of ABRAXAS1, ATM, BARD1, BLM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MEN1, MLH1, MRE11, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53, and XRCC2. In this study, we have compiled a collection of the missense variations reported in any of these 26 genes. More than a thousand missense variants were collected from ClinVar and the targeted screen of a breast cancer cohort of 355 patients which contributed to this set with 160 novel missense variations. We analyzed the impact of the missense variations on protein stability by five different predictors including both sequence- (SAAF2EC and MUpro) and structure-based (Maestro, mCSM, CUPSAT) predictors. For the structure-based tools, we have utilized the AlphaFold (AF2) protein structures which comprise the first structural analysis of this hereditary cancer proteins. Our results agreed with the recent benchmarks that computed the power of stability predictors in discriminating the pathogenic variants. Overall, we reported a low-to-medium-level performance for the stability predictors in discriminating pathogenic variants, except MUpro which had an AUROC of 0.534 (95% CI [0.499–0.570]). The AUROC values ranged between 0.614–0.719 for the total set and 0.596–0.682 for the set with high AF2 confidence regions. Furthermore, our findings revealed that the confidence score for a given variant in the AF2 structure could alone predict pathogenicity more robustly than any of the tested stability predictors with an AUROC of 0.852. Altogether, this study represents the first structural analysis of the 26 hereditary cancer genes underscoring 1) the thermodynamic stability predicted from AF2 structures as a moderate and 2) the confidence score of AF2 as a strong descriptor for variant pathogenicity.
Genome-wide identification and expression analysis of MADS-box transcription factors reveal their involvement in sex determination of hardy rubber tree (Eucommia ulmoides oliv.)
Authors: Zhang Xianzhi , Wang Xinyi , Pan Linsi , Guo Wei , Li Yongquan , Wang Wencai
Published: February 2023

Eucommia ulmoides is a famous rubber-producing and medicinal tree species that produces unisexual flowers on separate individuals from the earliest stage of stamen/pistil primordium formation. To explore the genetic regulation pathway of sex in E. ulmoides, comprehensive genome-wide analyses and tissue-/sex-specific transcriptome comparisons of MADS-box transcription factors were performed for the first time in this work. Quantitative real-time PCR technique was employed to further validate the expression of genes that are assigned to floral organ ABCDE model. A total of 66 non-redundant E. ulmoides MADS-box (EuMADS) genes were identified, they were classified into Type I (M-type, 17 genes) and Type II (MIKC, 49 genes). Complex protein-motif composition, exon-intron structure and phytohormone-response cis-elements were detected in MIKC-EuMADS genes. Furthermore, 24 differentially-expressed EuMADS genes (DEGs) between male and female flowers, and two DEGs between male and female leaves were revealed. Amongst the 14 floral organ ABCDE model-related genes, there were 6 (A/B/C/E-class) and 5 (A/D/E-class) genes displayed male- and female-biased expression respectively. In particular, one B-class gene EuMADS39 and one A-class gene EuMADS65 were almost exclusively expressed in male trees, no matter in flower or leaf tissues. Collectively, these results suggested a critical role of MADS-box transcription factors in sex determination of E. ulmoides, which is conducive to decoding the molecular regulation mechanism of sex in E. ulmoides.
Integration of bulk RNA sequencing and single-cell analysis reveals a global landscape of DNA damage response in the immune environment of Alzheimer’s disease
Authors: Lai Yongxing , Lin Han , Chen Manli , Lin Xin , Wu Lijuan , Zhao Yinan , Lin Fan , Lin Chunjin
Published: February 2023

Background

We developed a novel system for quantifying DNA damage response (DDR) to help diagnose and predict the risk of Alzheimer’s disease (AD).

Methods

We thoroughly estimated the DDR patterns in AD patients Using 179 DDR regulators. Single-cell techniques were conducted to validate the DDR levels and intercellular communications in cognitively impaired patients. The consensus clustering algorithm was utilized to group 167 AD patients into diverse subgroups after a WGCNA approach was employed to discover DDR-related lncRNAs. The distinctions between the categories in terms of clinical characteristics, DDR levels, biological behaviors, and immunological characteristics were evaluated. For the purpose of choosing distinctive lncRNAs associated with DDR, four machine learning algorithms, including LASSO, SVM-RFE, RF, and XGBoost, were utilized. A risk model was established based on the characteristic lncRNAs.

Results

The progression of AD was highly correlated with DDR levels. Single-cell studies confirmed that DDR activity was lower in cognitively impaired patients and was mainly enriched in T cells and B cells. DDR-related lncRNAs were discovered based on gene expression, and two different heterogeneous subtypes (C1 and C2) were identified. DDR C1 belonged to the non-immune phenotype, while DDR C2 was regarded as the immune phenotype. Based on various machine learning techniques, four distinctive lncRNAs associated with DDR, including FBXO30-DT, TBX2-AS1, ADAMTS9-AS2, and MEG3 were discovered. The 4-lncRNA based riskScore demonstrated acceptable efficacy in the diagnosis of AD and offered significant clinical advantages to AD patients. The riskScore ultimately divided AD patients into low- and high-risk categories. In comparison to the low-risk group, high-risk patients showed lower DDR activity, accompanied by higher levels of immune infiltration and immunological score. The prospective medications for the treatment of AD patients with low and high risk also included arachidonyltrifluoromethane and TTNPB, respectively,

Conclusions

In conclusion, immunological microenvironment and disease progression in AD patients were significantly predicted by DDR-associated genes and lncRNAs. A theoretical underpinning for the individualized treatment of AD patients was provided by the suggested genetic subtypes and risk model based on DDR.
Delivery of spike-RBD by bacterial type three secretion system for SARS-CoV-2 vaccine development
Authors: Zhou Yuchen , Qu Jing , Sun Xiaomeng , Yue Zhuo , Liu Yingzi , Zhao Keli , Yang Fan , Feng Jie , Pan Xiaolei , Jin Yongxin , Cheng Zhihui , Yang Liang , Ha Un-Hwan , Wu Weihui , Li Liang , Bai Fang
Published: February 2023

COVID-19 pandemic continues to spread throughout the world with an urgent demand for a safe and protective vaccine to effectuate herd protection and control the spread of SARS-CoV-2. Here, we report the development of a bacterial vector COVID-19 vaccine (aPA-RBD) that carries the gene for the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Live-attenuated strains of Pseudomonas aeruginosa (aPA) were constructed which express the recombinant RBD and effectively deliver RBD protein into various antigen presenting cells through bacterial type 3 secretion system (T3SS) in vitro. In mice, two-dose of intranasal aPA-RBD vaccinations elicited the development of RBD-specific serum IgG and IgM. Importantly, the sera from the immunized mice were able to neutralize host cell infections by SARS-CoV-2 pseudovirus as well as the authentic virus variants potently. T-cell responses of immunized mice were assessed by enzyme-linked immunospot (ELISPOT) and intracellular cytokine staining (ICS) assays. aPA-RBD vaccinations can elicit RBD-specific CD4+and CD8+T cell responses. T3SS-based RBD intracellular delivery heightens the efficiency of antigen presentation and enables the aPA-RBD vaccine to elicit CD8+T cell response. Thus, aPA vector has the potential as an inexpensive, readily manufactured, and respiratory tract vaccination route vaccine platform for other pathogens
Microbiology and immune mechanisms associated with male infertility
Authors: Chen Jin , Chen Jinyu , Fang Yiwei , Shen Qiuzi , Zhao Kai , Liu Chunyan , Zhang Huiping
Published: February 2023

Up to 50% of infertility is caused by the male side. Varicocele, orchitis, prostatitis, oligospermia, asthenospermia, and azoospermia are common causes of impaired male reproductive function and male infertility. In recent years, more and more studies have shown that microorganisms play an increasingly important role in the occurrence of these diseases. This review will discuss the microbiological changes associated with male infertility from the perspective of etiology, and how microorganisms affect the normal function of the male reproductive system through immune mechanisms. Linking male infertility with microbiome and immunomics can help us recognize the immune response under different disease states, providing more targeted immune target therapy for these diseases, and even the possibility of combined immunotherapy and microbial therapy for male infertility.
Spontaneous NETosis in diabetes: A role of hyperglycemia mediated ROS and autophagy
Authors: Farhan Anam , Hassan Ghulam , Ali Sheikha Hina Liaqat , Yousaf Zainab , Shafique Kandeel , Faisal Amir , Younis Bilal bin , Mirza Shaper
Published: February 2023

Type 2-diabetes, particularly poorly controlled diabetes, is a risk factor for several infections such as lower respiratory tract and skin infections. Hyperglycemia, a characteristic downstream effect of poorly controlled diabetes, has been shown to impair the function of immune cells, in particular neutrophils. Several studies have demonstrated that hyperglycemia-mediated priming of NADPH oxidase results in subsequent elevated levels of reactive oxygen species (ROS). In healthy neutrophils, ROS plays an important role in pathogen killing by phagocytosis and by induction of Neutrophil Extracellular Traps (NETs). Given the key role of ROS in autophagy, phagocytosis and NETosis, the relationship between these pathways and the role of diabetes in the modulation of these pathways has not been explored previously. Therefore, our study aimed to understand the relationship between autophagy, phagocytosis and NETosis in diabetes. We hypothesized that hyperglycemia-associated oxidative stress alters the balance between phagocytosis and NETosis by modulating autophagy. Using whole blood samples from individuals with and without type 2-diabetes (in the presence and absence of hyperglycemia), we demonstrated that (i) hyperglycemia results in elevated levels of ROS in neutrophils from those with diabetes, (ii) elevated levels of ROS increase LCIII (a marker for autophagy) and downstream NETosis. (iii) Diabetes was also found to be associated with low levels of phagocytosis and phagocytic killing of S. pneumoniae. (iv) Blocking either NADPH oxidase or cellular pathways upstream of autophagy led to a significant reduction in NETosis. This study is the first to demonstrate the role of ROS in altering NETosis and phagocytosis by modulating autophagy in type 2-diabetes.