bluuebunny/crossref_metadata_2025 huggingface dataset:
Indonesian and English Cultural Values in Buku Bahasa Inggris Textbook Grade 8
Authors: Qamarina Dian , Arianti Theresia
Published: September 2023

Textbooks play an important role in introducing students to various cultures. Majority of English teachers only concentrate on teaching four language skills rather than introducing culture to their students. It is critical to analyze cultural aspects in textbooks, particularly in English subjects, to ensure that the cultural values are represented in the English textbook. This study was conducted to find out multicultural values of the source culture and target culture that are represented in Buku Interaktif Bahasa Inggris, discover what techniques of multicultural values of the source culture and target culture are represented, and find out what culture is more represented in Buku Interaktif Bahasa Inggris. This study used content analysis method in order to collect and analyze the data. The result of this study shows that source culture is strongly represented in the textbooks, with National Geography as the multicultural value that mostly appears in the book, conveyed by Geographical Factors as the technique. This study could be useful for both teachers and authors as an input and evaluation so that cultural content can be included and considered in the textbooks or learning process.
Inserting Local Wisdom In English Material: Strategies and Benefits
Authors: Prayudha.S Joko
Published: September 2023

This study aims to describe the strategies and benefits of incorporating local cultural values in English language teaching. The type of research used is library research. Data was collected through reference collection from journals, articles, or books related to local culture in teaching. The analysis shows that the use of local cultural values is able to build student awareness of culture, encourage students to love the uniqueness and value of their culture, and improve their understanding of English material. The strategies that English teachers can apply when teaching using local culture are through materials related to products or objects typical of a region, such as using pictures or photos, conducting discussions, making video projects, practicing conversations, group learning, and making podcasts. Furthermore, the benefits that occur when including local wisdom in English teaching include increasing socio-cultural awareness, making students more aware of their culture and familiar materials, developing students' character, improving students' language skills, and increasing tolerance and mutual respect. To be successful in teaching English through local culture, teachers need to design and emphasize learning materials and activities using local culture so that students are more aware of the uniqueness of their culture.
Effects of Intercritical Heat Treatment on the Temper Embrittlement of SA508 Gr.4N Ni-Cr-Mo High Strength Low Alloy Steels for Reactor Pressure Vessels
Authors: Hong Seokmin , Lee Cho-Long , Lee Bong-Sang , Kim Hong-Deok , Kim Min-Chul
Published: September 2023

To analyze the effects of intercritical heat treatment on the temper embrittlement of SA508 Gr.4N steels, two model alloys with different phosphorus (P) contents were fabricated. Each sample was heat treated by applying a conventional heat treatment process (quenching-tempering) with/without an intercritical heat treatment process (IHT) and a step-cooling heat treatment for temper embrittlement. Then their microstructure and mechanical properties were evaluated. The microstructure of the SA508 Gr.4N model alloy was composed of tempered lower bainite and martensite, and nano-sized precipitates formed both inside and at boundaries. The grain size was reduced when IHT was applied. There was a small difference in tensile properties according to the heat-treatment conditions and P contents, but the difference in Charpy impact properties was large. The heat treatment for temper embrittlement (TE) increased the impact transition temperature, and a very significant increase was observed in steels with a high P content. The increase in transition temperature owing to TE was reduced when IHT was applied. The fractograph analysis of Charpy fractured specimens at transition temperatures showed that an increase in intergranular fracture was main reason for the TE, and that IHT reduced the formation of intergranular fracture. The AES results showed that P-Ni was segregated at grain boundaries, and the level of segregation was reduced by applying IHT. This occurred because the formation of prior austenite grain boundaries by IHT dispersed the P at grain boundaries, and reduced the amount of P segregation.
Classification of five different rice seeds grown in Turkey with deep learning methods
Authors: TUĞRUL Bülent
Published: September 2023

The increase in the world population and harmful environmental factors such as global warming necessitate a change in agricultural practices with the traditional method. Precision agriculture solutions offer many innovations to meet this increasing need. Using healthy, suitable and high-quality seeds is the first option that comes to mind in order to harvest more products from the fields. Seed classification is carried out in a labor-intensive manner. Due to the nature of this process, it is error-prone and also requires a high budget and time. The use of state-of-the-art methods such as Deep Learning in computer vision solutions enables the development of different applications in many areas. Rice is the most widely used grain worldwide after wheat and barley. This study aims to classify five different rice species grown in Turkey using four different Convolutional Neural Network (CNN) architectures. First, a new rice image dataset of five different species was created. Then, known and widely applied CNN architectures such as Visual Geometry Group (VGG), Residual Network (ResNet) and EfficientNets were trained and results were obtained. In addition, a new CNN architecture was designed and the results were compared with the other three architectures. The results showed that the VGG architecture generated the best accuracy value of 97%.
Entrevista com Ana Mercês Bahia Bock
Authors: Grigoleto Netto Jose Valdeci
Published: September 2023

Acredito que todas/os estudantes de Psicologia já se debruçaram em algum texto de Ana Mercês Bahia Bock durante sua jornada na graduação. Grande pesquisadora, Bock é nome de referência quando nos propomos a ler uma Psicologia ética, crítica e comprometida com o social. Recorrendo à minha história, enquanto cursava Psicologia, há pouco mais de uma década, fui apresentado aos seus escritos e me encantei: não apenas pelo conteúdo em si, mas pela forma na qual a escrita parecia deslizar no papel, de fácil leitura e entendimento; mas atenção: aqui, fácil não significa ausência de temas importantes, de dura leitura, densos. Esta é uma diferença crucial nos textos de Ana Bock: a possibilidade de transformar temas difíceis em um material fluído e acessível ao leitor.
Planejamento urbano: o caso do Jardim das Nações e Jardim Oásis na cidade de Paranavaí – PR
Authors: Vieira Chirlei Silva , Denardi Ana Maria , Lara Camila Clozato
Published: September 2023

Este trabalho buscou levantar, primeiramente, os dados urbanísticos e legais que envolvem o Jardim Oásis e o Jardim das Nações no município de Paranavaí e, na sequência, entender quais os problemas urbanos encontrados após seu loteamento e sua parcial ocupação. Para isso, está pesquisa buscou entender a problemática em torno das causas e das consequências da configuração urbana do Jardim das Nações e Jardim Oásis na cidade de Paranavaí - PR. Para tanto, utilizou-se a metodologia investigativa baseada na análise das legislações federais, estaduais e municipais a fim de identificar quais as diretrizes voltadas para a formação dos loteamentos e as características tipológicas das edificações predominantes desse espaço, concomitante com o levantamento bibliográfico a respeito do tema. Por fim, discutiu-se os fatores relevantes para a compreensão do panorama local: a existência de muitos vazios urbanos que dificultam a mobilidade urbana dos moradores da região; além da ausência de equipamentos urbanos para o atendimento de saúde, educação, lazer, cultura e a carências de mobiliários urbanos, todos esses dados fazem parte do crescimento desordenado existente na área de pesquisa.
Museus fechados: processos adaptativos e a ampliação da relevância e legitimidade institucional
Authors: Gabardo Junior Alcione , Silva Maclovia Corrêa da
Published: September 2023

Museus são instituições universais seculares que perceberam e incorporaram necessidades de adaptações constantes em suas práticas, como forma de afiançar sua relevância e legitimidade. Períodos de crises profundas provocam mudanças abruptas nos ambientes e exigem adaptação por parte das instituições. Os processos adaptativos são intencionais e devem ser norteados pela razoabilidade da intensidade das mudanças sob risco de perda da identidade e invisibilidade da instituição. Nesta perspectiva, surge a questão norteadora deste artigo ao questionar que práticas podem ser adotadas por instituições museológicas, em períodos de mudanças profundas, sem que tais práticas resultem em mudanças radicais nas finalidades institucionais? A metodologia adotada engloba uma discussão teórica sobre adaptação e mudanças nas instituições e a análise envolvendo a implementação de uma ação educativa por parte do Museu de Arte Indígena no contexto da crise sanitária provocada pela COVID-19. Destaca-se a ampliação das especialidades institucionais e consequente aumento da infusão de valores percebidos pelos atores com os quais o museu interage. Evidencia-se lacunas e oportunidades que afloram em ambientes de interação mesmo em períodos de crises profunda.
An empirical investigation of automation technology as material waste mitigation measure at Johor construction sites
Authors: Abkar Mahdi Mohammed Abdullah , Yunus Riduan , Al-Shameri Ahmed Saleh Ahmed Saif , Harouache Ahmed , Gamil Yaser
Published: September 2023

Automation technology in the construction industry is the use of advanced tools, devices, and processes that reduce manual labor and enhance efficiency in various construction activities. Automation technology can minimize waste, optimize resource utilization, and reduce the environmental impact of construction processes. This study aims to examine the relationship between automation technology adoptions (ATAs) utilizing reduce, reuse, and recycle (3R), building information modeling (BIM), industrialized building systems (IBSs), green building index (GBI), and Internet of Things (IoT) practices toward construction site performance (CSP) to measure their influences on material waste mitigation measures at Johor construction sites. To achieve these goals, five hypotheses were developed to explore the association between ATA and CSP. Data were gathered utilizing an online survey. The participants were contractors and expert practitioners in the Johor construction industry, including architects, project managers, and academicians/researchers. A total of 257 valid responses were used to investigate the assumptions. The partial least squares structural equation modeling (PLS-SEM) procedure was used. The findings revealed that ATA utilizing 3R, BIM, IBS, GBI, and IoT as material mitigation measures positively enhances CSP.
Role of the epithelial barrier in intestinal fibrosis associated with inflammatory bowel disease: relevance of the epithelial-to mesenchymal transition
Authors: Macias-Ceja Dulce C. , Mendoza-Ballesteros M. Teresa , Ortega-Albiach María , Barrachina M. Dolores , Ortiz-Masià Dolores
Published: September 2023

In inflammatory bowel disease (IBD), chronic inflammation in the gastrointestinal tract can lead to tissue damage and remodelling, which can ultimately result in fibrosis. Prolonged injury and inflammation can trigger the activation of fibroblasts and extracellular matrix (ECM) components. As fibrosis progresses, the tissue becomes increasingly stiff and less functional, which can lead to complications such as intestinal strictures, obstructive symptoms, and eventually, organ dysfunction. Epithelial cells play a key role in fibrosis, as they secrete cytokines and growth factors that promote fibroblast activation and ECM deposition. Additionally, epithelial cells can undergo a process called epithelial-mesenchymal transition, in which they acquire a more mesenchymal-like phenotype and contribute directly to fibroblast activation and ECM deposition. Overall, the interactions between epithelial cells, immune cells, and fibroblasts play a critical role in the development and progression of fibrosis in IBD. Understanding these complex interactions may provide new targets for therapeutic interventions to prevent or treat fibrosis in IBD. In this review, we have collected and discussed the recent literature highlighting the contribution of epithelial cells to the pathogenesis of the fibrotic complications of IBD, including evidence of EMT, the epigenetic control of the EMT, the potential influence of the intestinal microbiome in EMT, and the possible therapeutic strategies to target EMT. Finally we discuss the pro-fibrotic interactions epithelial-immune cells and epithelial-fibroblasts cells.
Engagement of atrial fibrillation patients with the AF-EduApp, a new mobile application to support AF management
Authors: Knaepen Lieselotte , Delesie Michiel , Theunis Rik , Gorissen Peter , Vijgen Johan , Dendale Paul , Desteghe Lien , Heidbuchel Hein
Published: September 2023

Introduction

A multidisciplinary approach is needed for the management of atrial fibrillation (AF) in which the patient has a central role. Smart devices create opportunities to improve AF management. This paper aimed to evaluate the in-house developed AF-EduApp application on its usability, satisfaction, and communication effectiveness with the care team.

Methods

During a multicenter, prospective randomized controlled trial, 153 AF patients were included in the AF-EduApp study, with a minimum follow-up of 12 months and a maximum follow-up of 15 months if taking oral anticoagulation (OAC). The AF-EduApp contains six main modules: Questionnaires, Education, Measurement data entry, Medication overview with reminders, Appointments, and Communication with the care team. The App focuses on four main goals: (1) to improve AF knowledge, (2) to increase self-care capabilities, (3) electronic monitoring to improve therapy adherence to OAC, and (4) communication with the care team. Patients unable to use the AF-EduApp were assigned to a no-App control group (n = 41) without intervention comparable to the standard care group (SC, n = 346) of the AF-EduCare study.

Results

A total of 152 patients effectively used the App during a mean follow-up of 386.8 ± 108. 1 days (one included patient could not install the application due to an iPhone from the United States). They opened the application on average on 130.1 ± 144.7 days. Of the 109 patients still in follow-up after 12 months (i.e. patients who did not withdraw and on OAC), 90 patients (82.6%) actively used the application at least one day in the next 41 days. The Measurement module was the most used, with a median of used days over the total available days of 6.4%. A total of 75 App patients (49.3%) asked questions, mostly clinical-related questions (e.g. medication use, or actionability on clinical entered parameters). A mean score of 8.1 ± 1.7 about the “perceived quality of follow-up in the past year” was given by the App ITT patients, compared to a score of 7.7 ± 2.0 by the SC group (P = .072). Patients who used the App were more attracted to future follow-up with an application compared to patients who would be capable of using the application of the SC group (31.6% vs. 12.5%; P < .001).

Conclusion

This study showed a positive attitude towards using a mobile application, with AF patients using the application one-third of the available days. Patients used the App most for entering measured parameters, and to contact the care team.
Implementing internet-delivered cognitive behavioral therapy in healthcare services: a qualitative exploration of stakeholder experience
Authors: Duffy Daniel , Richards Derek , Earley Caroline , Timulak Ladislav
Published: September 2023

Background

This study consisted of a qualitative exploration of stakeholder experience regarding the implementation of internet-delivered cognitive behavioral therapy (iCBT) as part of routine service provision within the UK's Improving Access to Psychological Therapies program.

Methods

Stakeholder groups included service providers (n = 6), commercial iCBT representatives (n = 6) and patients who received a course of iCBT as part of treatment at the service (n = 7). Participants took part in a semi-structured interview over the telephone, and subsequent data were qualitatively analyzed using the descriptive-interpretive approach.

Results

Service providers highlighted the importance of effective leadership and management, training initiatives, the provision of feedback to commercial iCBT representatives and creating work structures around iCBT to facilitate iCBT supporting staff in their use of it. Commercial iCBT representatives similarly reported the importance of training clinicians in iCBT use, identifying the appropriate individuals at all levels of the service to drive iCBT implementation, and the importance of being responsive to any problems or needs that arise from the service. Patients reported an overall positive experience of receiving iCBT but highlighted a need for more information from their supporter and the intervention to better structure their usage. Contextual factors, in terms of barriers and facilitators, were also highlighted by service provider and commercial participants; citing negative clinician attitudes and technological issues/bugs as barriers to implementation, and the exposure to iCBT created by COVID-19 and perseverance in using iCBT over time as facilitators.

Discussion

The findings contribute to a growing field of literature that seeks to understand the experience of relevant stakeholders who are involved with and contribute to iCBT implementation, including commercial iCBT representatives who, to our knowledge, have not been accounted for as part of published research to date.
Temperature-responsive PCL-PLLA nanofibrous tissue engineering scaffolds with memorized porous microstructure recovery
Authors: Woodbury Seth M. , Swanson W. Benton , Douglas Lindsey , Niemann David , Mishina Yuji
Published: September 2023

Biomaterial scaffolds in tissue engineering facilitate tissue regeneration and integration with the host. Poor healing outcomes arise from lack of cell and tissue infiltration, and ill-fitting interfaces between matrices or grafts, resulting in fibrous tissue formation, inflammation, and resorption. Existing tissue engineering scaffolds struggle to recover from deformation to fit irregularly shaped defects encountered in clinical settings without compromising their mechanical properties and favorable internal architecture. This study introduces a synthetic biomaterial scaffold composed of high molecular weight poly (L-lactic acid) (PLLA) and an interpenetrating network of poly (ε-caprolactone) (PCL), in a composition aiming to address the need for conformal fitting synthetic matrices which retain and recover their advantageous morphologies. The scaffold, known as thermosensitive memorized microstructure (TS-MMS), forms nanofibrous materials with memorized microstructures capable of recovery after deformation, including macropores and nanofibers. TS-MMS nanofibers, with 50–500 nm diameters, are formed via thermally induced phase separation (TIPS) of PLLA after in situ polymerization of PCL-diacrylate. A critical partial-melting temperature of TS-MMS at 52°C enables bulk deformation above this temperature, while retaining the nanofibrous and macroporous structures upon cooling to 37°C. Incorporation of drug-loaded poly (lactide-co-glycolide) (PLGA) nanoparticles directly into TS-MMS nanofibers during fabrication allows sustained release of a model drug for up to 40 days. Subcutaneous implantation in vivo using LysM-Cre;td-Tomato; Col1eGFP mice demonstrates successful cellularization and integration of deformed/recovered TS-MMS materials, surpassing the limitations of deformed PLLA scaffolds, to facilitate cell and vasculature infiltration requisite for successful bone regeneration. Additionally we demonstrated a method for embedding controlled release vehicles directly into the scaffold nanofibers; controlled release of simvastatin enhances vascularization and tissue maturation. TS-MMS scaffolds offer promising improvements in clinical handling and performance compared to existing biomaterial scaffolds.
Endometrial receptivity change: ultrasound evaluation on ovulation day and transplantation day during the natural frozen embryo transfer cycle
Authors: Li Xihong , Peng Yangqin , Mao Yuyao , Li Yuan , Gong Fei , Ouyang Yan
Published: September 2023

Objective

To obtain quantitative and comprehensive results of the changes in comprehensive ER indicators from ovulation day to transplantation day by ultrasonography during the natural frozen-thawed embryo transfer cycle (FET).

Methods

This is a prospective analysis of 230 infertile women undergoing their first FET cycles from April 2019 to July 2021. To evaluate ER, ultrasound scans were performed on the days of ovulation and embryo transfer for all included patients. All included patients were divided into a pregnancy group and a nonpregnancy group according to whether clinical pregnancy was achieved. The ER changes from ovulation day to transplantation day in the overall study population (n=230), pregnancy group (n=158) and nonpregnancy group (n=72) were analyzed.

Results

In the overall population, type C was predominant on ovulation day, but type B was the most common on transplantation day (P<0.001). From ovulation day to transplantation day, endometrial thickness was significantly increased (11.26 ± 2.14 vs. 11.89 ± 2.08 mm, P<0.001), but endometrial volume (4.26 ± 1.75 vs. 4.03 ± 1.62 ml, P<0.001), endometrial VI (1.34 ± 1.64 vs. 0.95 ± 1.99, P<0.001), VFI (0.47 ± 0.72 vs. 0.40 ± 1.03, P<0.001), subendometrial VI (5.04 ± 3.89 vs. 3.29 ± 2.92, P<0.001), FI (34.07 ± 4.61 vs. 33.41 ± 5.30, p=0.004), VFI (2.07 ± 2.65 vs. 1.19 ± 1.19, P<0.001) and frequency of endometrial peristalsis (2.90 ± 1.44 vs. 1.40 ± 1.41, P<0.001) were significantly decreased. In the pregnancy group, the changes in all ultrasound parameters were in the same direction as those in the overall population. In the nonpregnancy group, except for endometrial volume and VI, which showed no difference, other ultrasound parameters showed the same direction of change as those in the overall population. No significant difference was found in the pregnancy probability among the different absolute change groups.

Conclusion

During a natural cycle, the morphology of the endometrium changes mostly from type C to type B, the endometrial thickness increases, and the volume decreases. The blood supply of the endometrium, the subendometrial 5 mm and the frequency of peristalsis decrease from ovulation day to transplantation day. Compared with the nonpregnancy group, the pregnancy group tended to have more obvious decreases in endometrial volume and blood flow perfusion. However, these endometrial changes do not mean that pregnancy is bound to occur. endometrial receptivity, in vitro fertilization, frozen-thawed embryo transfer, natural cycle, ultrasound evaluation, ovulation day, transplantation day
The relationship between frequent premature ventricular complexes and epicardial adipose tissue volume
Authors: Wang Zhe , Jiao Siqi , Chen Jiawei , Guo Hehe , Ren Lichen , Sun Liping , Sun Yihong , Chen Yingwei
Published: September 2023

Background

Epicardial adipose tissue (EAT) is related to atrial fibrillation. The association between EAT volume and premature ventricular complexes (PVCs) remains unclear. Our study aimed to investigate the effect of EAT volume on the risk of frequent PVCs and burden levels of PVCs.

Methods

This observational study retrospectively recruited consecutive patients who had consultation between 2019 and 2021 at the First Affiliated Hospital of Zhengzhou University. Frequent PVC patients (n = 402) and control patients (n = 402) undergoing non-contrast computed tomography (CT) were enrolled. We selected evaluation criteria for the conduct of a 1:1 propensity score matching (PSM) analysis. Multivariable logistic analysis was used to investigate factors related to frequent PVCs. Furthermore, the determinants of EAT volume and the burden levels of PVCs were evaluated.

Results

Patients with PVCs had a significantly larger EAT volume than control patients. EAT volume was significantly larger in male PVC patients with BMI ≥24 kg/m2, diabetes mellitus, and E/A ratio <1. EAT volume was independently associated with PVCs. Moreover, the larger EAT volume was an independent predictor for the high burden level of PVCs. We revealed that the risk of high PVC burden level was increased with the rising of EAT volume by restricted cubic splines.

Conclusions

EAT volume was larger in frequent PVC patients than in control patients, regardless of other confounding factors. A large EAT volume was independently associated with high burden levels of PVCs. EAT volume may be a new mechanism to explain the pathogenesis of PVCs.
Research on the impact of fiscal environmental protection expenditure on agricultural carbon emissions
Authors: Wu Saijun , Chen Xueqing
Published: September 2023

China’s agricultural and rural greenhouse gas emissions account for about 15% of its total emissions. Studying how to reduce China’s agricultural carbon emissions (ACEs) is of great strategic significance. Based on the panel data of 31 provinces (cities) in China from 2007 to 2020, this paper empirically tests the impact of fiscal environmental protection expenditure (FEPE) on ACEs. The results reveal that: FEPE has significant negative impacts on ACEs; FEPE has a heterogeneous impact on ACEs in different regions, which shows that it has a significant impact on the eastern and central regions and provinces with relatively “high” carbon emissions, while it has no significant impact on the western regions and provinces with relatively “low” carbon emissions; Further the results of mechanism analysis show that the impact of FEPE on ACEs is mainly manifested in its inhibiting effect on agricultural diesel, fertilizer and film use of carbon emissions. In light of these findings, it is imperative for the government to ensure steady and substantial investments in environmental protection. Moreover, implementing region-specific measures is essential to effectively curbing ACEs. The findings of this study offer invaluable insights that can guide the formulation of policies aimed at effectively reducing ACEs.
Chemical and population genetic analysis show no evidence of ecotype formation in a European population of the parasitoid wasp Nasonia vitripennis
Authors: Buellesbach Jan , Lammers Mark , van de Belt José , Pannebakker Bart A.
Published: September 2023

Ecotypes, subpopulations or strains of a single species locally adapted to divergent ecological conditions within the same habitat are often considered to be the first steps in sympatric speciation. It has been suggested that two ecotypes are distinguishable in Nasonia vitripennis, a prominent model organism for parasitic Hymenoptera, with one ecotype parasitizing fly pupae in bird nests, and the other one parasitizing fly pupae on carrion. This differentiation into two ecotypes has been hypothesized to indicate incipient sympatric speciation in populations of this globally distributed species. In the present study, we investigated the differentiation into these two distinct ecotypes focusing on chemical profiles and the population genetic divergence in a wild N. vitripennis population from the Netherlands. Isofemale lines were obtained from bird nest boxes and from deer carrion, respectively, representing both microhabitats. To test for phenotypic differentiation, we determined the surface cuticular hydrocarbon (CHC) profiles from wasps of both host patches. Using a panel of 14 microsatellites, we concordantly determined the population genetic structure and tested for genetic differentiation between foundresses obtained from both microhabitats. Both the phenotypic as well as the genetic datasets show no evidence for any kind of separation based on the postulated two ecotypes, but rather suggest free interbreeding with no gene flow interruption between the two distinct host patches. Our findings challenge previous assumptions on clearly distinguishable ecotypes in N. vitripennis, and demonstrate how a chemical ecological assessment coupled with population genetics can be instrumental in re-evaluating the potential of ecological differentiation and incipient speciation mechanisms in parasitoid wasps.
Short-term assays for mesenchymal stromal cell immunosuppression of T-lymphocytes
Authors: Herzig Maryanne C. , Christy Barbara A. , Montgomery Robbie K. , Cantu-Garza Carolina , Barrera Gema D. , Lee Ji H. , Mucha Nicholas , Talackine Jennifer R. , Abaasah Isaac A. , Bynum James A. , Cap Andrew P.
Published: September 2023

Introduction

Trauma patients are susceptible to coagulopathy and dysfunctional immune responses. Mesenchymal stromal cells (MSCs) are at the forefront of the cellular therapy revolution with profound immunomodulatory, regenerative, and therapeutic potential. Routine assays to assess immunomodulation activity examine MSC effects on proliferation of peripheral blood mononuclear cells (PBMCs) and take 3–7 days. Assays that could be done in a shorter period of time would be beneficial to allow more rapid comparison of different MSC donors. The studies presented here focused on assays for MSC suppression of mitogen-stimulated PBMC activation in time frames of 24 h or less.

Methods

Three potential assays were examined—assays of apoptosis focusing on caspase activation, assays of phosphatidyl serine externalization (PS+) on PBMCs, and measurement of tumor necrosis factor alpha (TNFα) levels using rapid ELISA methods. All assays used the same initial experimental conditions: cryopreserved PBMCs from 8 to 10 pooled donors, co-culture with and without MSCs in 96-well plates, and PBMC stimulation with mitogen for 2–72 h.

Results

Suppression of caspase activity in activated PBMCs by incubation with MSCs was not robust and was only significant at times after 24 h. Monitoring PS+ of live CD3+ or live CD4+/CD3+ mitogen-activated PBMCs was dose dependent, reproducible, robust, and evident at the earliest time point taken, 2 h, although no increase in the percentage of PS+ cells was seen with time. The ability of MSC in co-culture to suppress PBMC PS+ externalization compared favorably to two concomitant assays for MSC co-culture suppression of PBMC proliferation, at 72 h by ATP assay, or at 96 h by fluorescently labeled protein signal dilution. TNFα release by mitogen-activated PBMCs was dose dependent, reproducible, robust, and evident at the earliest time point taken, with accumulating signal over time. However, suppression levels with MSC co-culture was reliably seen only after 24 h.

Discussion

Takeaways from these studies are as follows: (1) while early measures of PBMC activation is evident at 2–6 h, immunosuppression was only reliably detected at 24 h; (2) PS externalization at 24 h is a surrogate assay for MSC immunomodulation; and (3) rapid ELISA assay detection of TNFα release by PBMCs is a robust and sensitive assay for MSC immunomodulation at 24 h.
The evolution of antimicrobial peptides in Chiroptera
Authors: Castellanos Francisco X. , Moreno-Santillán Diana , Hughes Graham M. , Paulat Nicole S. , Sipperly Nicolette , Brown Alexis M. , Martin Katherine R. , Poterewicz Gregory M. , Lim Marisa C. W. , Russell Amy L. , Moore Marianne S. , Johnson Matthew G. , Corthals Angelique P. , Ray David A. , Dávalos Liliana M.
Published: September 2023

High viral tolerance coupled with an extraordinary regulation of the immune response makes bats a great model to study host-pathogen evolution. Although many immune-related gene gains and losses have been previously reported in bats, important gene families such as antimicrobial peptides (AMPs) remain understudied. We built an exhaustive bioinformatic pipeline targeting the major gene families of defensins and cathelicidins to explore AMP diversity and analyze their evolution and distribution across six bat families. A combination of manual and automated procedures identified 29 AMP families across queried species, with α-, β-defensins, and cathelicidins representing around 10% of AMP diversity. Gene duplications were inferred in both α-defensins, which were absent in five species, and three β-defensin gene subfamilies, but cathelicidins did not show significant shifts in gene family size and were absent in Anoura caudifer and the pteropodids. Based on lineage-specific gains and losses, we propose diet and diet-related microbiome evolution may determine the evolution of α- and β-defensins gene families and subfamilies. These results highlight the importance of building species-specific libraries for genome annotation in non-model organisms and shed light on possible drivers responsible for the rapid evolution of AMPs. By focusing on these understudied defenses, we provide a robust framework for explaining bat responses to pathogens.
Identification and validation of potential diagnostic signature and immune cell infiltration for NAFLD based on cuproptosis-related genes by bioinformatics analysis and machine learning
Authors: Ouyang Guoqing , Wu Zhan , Liu Zhipeng , Pan Guandong , Wang Yong , Liu Jing , Guo Jixu , Liu Tao , Huang Guozhen , Zeng Yonglian , Wei Zaiwa , He Songqing , Yuan Guandou
Published: September 2023

Background and aims

Cuproptosis has been identified as a key player in the development of several diseases. In this study, we investigate the potential role of cuproptosis-related genes in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).

Method

The gene expression profiles of NAFLD were obtained from the Gene Expression Omnibus database. Differential expression of cuproptosis-related genes (CRGs) were determined between NAFLD and normal tissues. Protein–protein interaction, correlation, and function enrichment analyses were performed. Machine learning was used to identify hub genes. Immune infiltration was analyzed in both NAFLD patients and controls. Quantitative real-time PCR was employed to validate the expression of hub genes.

Results

Four datasets containing 115 NAFLD and 106 control samples were included for bioinformatics analysis. Three hub CRGs (NFE2L2, DLD, and POLD1) were identified through the intersection of three machine learning algorithms. The receiver operating characteristic curve was plotted based on these three marker genes, and the area under the curve (AUC) value was 0.704. In the external GSE135251 dataset, the AUC value of the three key genes was as high as 0.970. Further nomogram, decision curve, calibration curve analyses also confirmed the diagnostic predictive efficacy. Gene set enrichment analysis and gene set variation analysis showed these three marker genes involved in multiple pathways that are related to the progression of NAFLD. CIBERSORT and single-sample gene set enrichment analysis indicated that their expression levels in macrophages, mast cells, NK cells, Treg cells, resting dendritic cells, and tumor-infiltrating lymphocytes were higher in NAFLD compared with control liver samples. The ceRNA network demonstrated a complex regulatory relationship between the three hub genes. The mRNA level of these hub genes were further confirmed in a mouse NAFLD liver samples.

Conclusion

Our study comprehensively demonstrated the relationship between NAFLD and cuproptosis, developed a promising diagnostic model, and provided potential targets for NAFLD treatment and new insights for exploring the mechanism for NAFLD.
Spoilt for choice: different immunosuppressive potential of anaplastic lymphoma kinase inhibitors for non small cell lung cancer
Authors: Heine Annkristin , Held Stefanie Andrea Erika , Daecke Solveig Nora , Flores Chrystel , Brossart Peter
Published: September 2023

Introduction

Several anaplastic lymphoma kinase (ALK)-inhibitors (ALKi) have been approved for the treatment of ALK-translocated advanced or metastatic Non Small Cell Lung Cancer (NSCLC), amongst crizotinib and alectinib. This forces physicians to choose the most suitable compound for each individual patient on the basis of the tumor´s genetic profile, but also in regard to toxicities and potential co-treatments. Moreover, targeted therapies might be combined with or followed by immunotherapy, which underlines the importance to gain detailed knowledge about potential immunomodulatory effects of these inhibitors. We here aimed to 1.) determine whether ALKi display an immunosuppressive effect on human dendritic cells (DCs) as important mediators of antigen-specific immunity and to 2.) dissect whether this immunosuppression differs among ALKi.

Methods

We investigated the effect of alectinib and crizotinib on human monocyte-derived DCs (moDC) as most powerful antigen-presenting cells. We performed immunophenotyping by flow cytometry, migration, antigen uptake and cytokine assays.

Results

Crizotinib-treated DCs showed reduced activation markers, such as CD83, decreased chemokine-guided migration, lower antigen uptake and produced inferior levels of pro-inflammatory cytokines, especially Interleukin-12. In contrast, the immunosuppressive potential of alectinib was significantly less pronounced. This indicates that crizotinib might profoundly dampen anti-tumor immunity, while alectinib had no unfavourable immunosuppressive effects.

Conclusions

Our results implicate that current ALKi differ in their capacity to suppress the activation, migration and cytokine production of DCs as essential mediators of T cell immunity. We show that crizotinib, but not alectinib, had immunosuppressive effects on DCs phenotype and reduced DC function, thereby potentially impairing anti-tumor immunity.
Senescence risk score: a multifaceted prognostic tool predicting outcomes, stemness, and immune responses in colorectal cancer
Authors: Zhang Xiaojun , Huang Yilan , Li Qian , Zhong Yiqing , Zhang Yuanzhou , Hu Jingying , Liu Rui , Luo Xiaoying
Published: September 2023

Colorectal cancer (CRC) remains a primary cause of cancer mortality globally, necessitating precise prognostic indicators for effective clinical management. Our study introduces the Senescence Risk Score (SRRS), based on several senescence-related genes (SRGs), a potent prognostic tool designed to measure cellular senescence in CRC. The higher SRRS predicts a poorer prognosis, providing a novel and efficient approach to patient stratification. Notably, we found that SRRS correlates with methylation and mutation variations, and increased immune infiltration in the tumor microenvironment, thus revealing potential therapeutic targets. We also discovered an inverse relationship between SRRS and cell stemness, which could have significant implications for cancer treatment strategies. Utilizing bioinformatics resources and machine learning, we identified LIMK1 and WRN as key genes associated with SRRS, further enhancing its prognostic value. Importantly, the modulation of these genes significantly impacts cellular senescence, proliferation, and stemness in CRC cells. In summary, our development of SRRS offers a powerful tool for CRC prognosis and paves the way for novel therapeutic strategies, underscoring its potential in transforming CRC patient management.
Research on integrated coastal zone management from past to the future: a bibliometric analysis
Authors: Jiang Lu , Yang Tang , Wang Xuyi , Yu Jing , Liu Jia , Zhang Kuncheng
Published: September 2023

Integrated coastal zone management (ICZM) has been regarded as an effective tool for achieving sustainable development of coastal ecosystems and reducing potential human health risks, but questions remain regarding its research status and future directions. Therefore, a bibliometric analysis was conducted using screened 6151 publications collected from Web of Science Core Collection databases. An exponential increase trend of publications revealed the continuous and strong research interests for ICZM worldwide. The most high-yield country, institution, category, and journal were USA, NOAA, Environmental Sciences, and Ocean & Coastal Management, respectively. Regarding the number of publications, academic influence, and international collaboration, the developed countries occupied the predominant positions. Co-word analysis reveals eight important topics: challenge, service, management and planning, method and technology, development, process, area, and system. Relevant future directions of the ICZM field were proposed based on the Sustainable Development Goals of the United Nations. This review addresses the question of what focal topics in the ICZM field and what should be focused on in future works by objective and quantitative methods. Our results provide valuable insights into the evolution of the ICZM field and the sustainable development of the coastal areas.
Butchering activity is the main risk factor for hepatitis E virus (Paslahepevirus balayani) infection in southwestern Nigeria: a prospective cohort study
Authors: Oluremi Adeolu S. , Casares-Jimenez Maria , Opaleye Oluyinka O. , Caballero-Gomez Javier , Ogbolu David Olusoga , Lopez-Lopez Pedro , Corona-Mata Diana , Rivero-Juarez Antonio , Rivero Antonio
Published: September 2023

Introduction

Paslahepevirus balayani (Hepatitis E virus; HEV) is an emerging virus that poses as a public health threat. The virus is now reported to be the leading cause of acute viral hepatitis, with a unique impact on African settings. Our aim was to evaluate the prevalence and risk factors for HEV infection in three cohorts (animal handlers, villagers, and students).

Methods

A prospective cross-sectional study was carried out on a total of 752 subjects from southwestern Nigeria. In all individuals, anti-HEV IgG and anti-HEV IgM antibodies were evaluated by using ELISA (confirming positive results via immunoblotting), and serum viral RNA was evaluated by using two RT-PCR assays.

Results

The overall seroprevalence of HEV IgG and HEV IgM was 14.9% (95% CI: 12.5–17.6%) and 1.3% (95% CI: 0.7–2.5%), respectively. We observed the highest seroprevalence among animal contact individuals, with butchers being the population with the highest HEV IgG seroprevalence (31.1%). Similarly, HEV IgM was higher in the animal contact group (2.2%) than in the non-animal contact cohort (0%).

Discussions

Viral RNA was not detected in any of the samples. Butchering was significantly associated with higher HEV prevalence. Although all efforts to prevent HEV in Africa have focused on the chlorination of water, our study suggests that most new infections could currently be linked to animal manipulation. Therefore, education and guidelines must be provided in southwest Nigeria to ensure that animal handling and processing methods are safe.
Effect of sublethal dose of chloramphenicol on biofilm formation and virulence in Vibrio parahaemolyticus
Authors: Zhang Miaomiao , Cai Liyan , Luo Xi , Li Xue , Zhang Tingting , Wu Fei , Zhang Yiquan , Lu Renfei
Published: September 2023

Vibrio parahaemolyticus isolates are generally very sensitive to chloramphenicol. However, it is usually necessary to transfer a plasmid carrying a chloramphenicol resistance gene into V. parahaemolyticus to investigate the function of a specific gene, and the effects of chloramphenicol on bacterial physiology have not been investigated. In this work, the effects of sublethal dose of chloramphenicol on V. parahaemolyticus were investigated by combined utilization of various phenotypic assays and RNA sequencing (RNA-seq). The results showed that the growth rate, biofilm formation capcity, c-di-GMP synthesis, motility, cytoxicity and adherence activity of V. parahaemolyticus were remarkably downregulated by the sublethal dose of chloramphenicol. The RNA-seq data revealed that the expression levels of 650 genes were significantly differentially expressed in the response to chloramphenicol stress, including antibiotic resistance genes, major virulence genes, biofilm-associated genes and putative regulatory genes. Majority of genes involved in the synthesis of polar flagellum, exopolysaccharide (EPS), mannose-sensitive haemagglutinin type IV pilus (MSHA), type III secretion systems (T3SS1 and T3SS2) and type VI secretion system 2 (T6SS2) were downregulated by the sublethal dose of chloramphenicol. Five putative c-di-GMP metabolism genes were significantly differentially expressed, which may be the reason for the decrease in intracellular c-di-GMP levels in the response of chloramphenicol stress. In addition, 23 genes encoding putative regulators were also significantly differentially expressed, suggesting that these regulators may be involved in the resistance of V. parahaemolyticus to chloramphenicol stress. This work helps us to understand how chloramphenicol effect on the physiology of V. parahaemolyticus.
A homozygous missense variant in the YG box domain in an individual with severe spinal muscular atrophy: a case report and variant characterization
Authors: Li Leping , Perera Lalith , Varghese Sonia A. , Shiloh-Malawsky Yael , Hunter Senyene E. , Sneddon Tam P. , Powell Cynthia M. , Matera A. Gregory , Fan Zheng
Published: September 2023

The vast majority of severe (Type 0) spinal muscular atrophy (SMA) cases are caused by homozygous deletions of survival motor neuron 1 (SMN1). We report a case in which the patient has two copies of SMN1 but clinically presents as Type 0 SMA. The patient is an African American male carrying a homozygous maternally inherited missense variant (c.796T>C) in a cis-oriented SMN1 duplication on one chromosome and an SMN1 deletion on the other chromosome (genotype: 2*+0). Initial extensive genetic workups including exome sequencing were negative. Deletion analysis used in the initial testing for SMA also failed to detect SMA as the patient has two copies of SMN1. Because of high clinical suspicion, SMA diagnosis was finally confirmed based on full-length SMN1 sequencing. The patient was initially treated with risdiplam and later gene therapy with onasemnogene abeparvovec at 5 months without complications. The patient’s muscular weakness has stabilized with mild improvement. The patient is now 28 months old and remains stable and diffusely weak, with stable respiratory ventilatory support. This case highlights challenges in the diagnosis of SMA with a non-deletion genotype and provides a clinical example demonstrating that disruption of functional SMN protein polymerization through an amino acid change in the YG-box domain represents a little known but important pathogenic mechanism for SMA. Clinicians need to be mindful about the limitations of the current diagnostic approach for SMA in detecting non-deletion genotypes.