bluuebunny/crossref_metadata_2025 huggingface dataset:
Special Education Personnel Preparation in Singapore
Authors: Lim Levan , Thaver Thana , Loh Pek Ru
Published: June 2024

Special education in Singapore has evolved considerably during the past two decades with greater enrollments of students with special educational needs in regular mainstream schools. This progressive transformation in Singapore’s education towards the inclusion of students with special needs in mainstream classes has been accompanied by concomitant changes in teacher preparation programs for both general and special education teachers and professionals. This article situates and describes special education in Singapore and its increasing role in partnering with mainstream education within Singapore’s socio-historical context and evolvement as a nation since independence. Current issues related to special education and its expanding role in preparing teachers and related professionals for working with students with special educational needs in both mainstream and special schools are discussed with implications raised for future directions.
Đầu tư và chi phí đại diện: Trường hợp các doanh nghiệp niêm yết Việt Nam
Authors: Phạm Xuân Quỳnh , Trương Đông Lộc , Lê Long Hậu
Published: June 2024

Nghiên cứu được thực hiện nhằm đánh giá đầu tư của doanh nghiệp và phân tích ảnh hưởng của chi phí đại diện đến đầu tư. Dữ liệu nghiên cứu được thu thập từ các doanh nghiệp niêm yết trong giai đoạn từ 2013-2022. Với phương pháp ước lượng bình phương tối thiểu tổng quát (GLS), trước tiên, kết quả cho thấy đầu tư phụ thuộc vào nguồn tài chính nội bộ, do đó thị trường tài chính Việt Nam là không hoàn hảo, dẫn đến các doanh nghiệp có thể phải đối mặt với vấn đề chi phí đại diện. Tiếp theo, kết quả chỉ ra rằng so với các doanh nghiệp có chi phí đại diện thấp, các doanh nghiệp có chi phí đại diện cao hơn thì độ nhạy cảm của đầu tư đối với nguồn tài chính nội bộ là lớn hơn. Hàm ý, việc thặng dự nguồn tài chính nội bộ sẽ ảnh hưởng đến mức độ đầu tư, các doanh nghiệp có chi phí đại diện lớn và thặng dư vốn nội bộ có nhiều khả năng sẽ đầu tư quá mức.
Sosiaalityön ammattilaisten näkemyksiä asumisesta ja siihen liittyvästä huono-osaisuudesta
Authors: Kivipelto Minna , Ilmarinen Katja , Karjalainen Pekka
Published: June 2024

Asumiseen liittyvä huono-osaisuus näkyy aikuissosiaalityössä päivittäin. Vaikeimmassa asemassa ovat henkilöt, joilla mielenterveyden häiriöt, päihteet, asumisen ongelmat ja taloudelliset vaikeudet kietoutuvat yhteen. Vuokra-asuntojen ja palvelujen sijoittelu sekä Kelan asumiskulujen normit vaikeuttavat poispääsyä huono-osaisuudesta. Asumiseen liittyvien ongelmien syntyä tulisi ehkäistä toimivalla yhdyskuntasuunnittelulla, jossa olisi hyödynnettävä nykyistä enemmän myös sosiaalityön asiantuntemusta.
Meningkatkan Kemampuan Literasi Numerasi Mahasiswa Melalui Media Elektronik Flip Bookmaker
Authors: Sibua Sulami , Suharna Hery
Published: June 2024

Permasalahan yang dihadapi mahasiswa saat ini adalah sulitnya melaksanakan pembiasaan literasi bagi mahasiswa ketika pembelajaran, rendahnya minat baca mahasiswa, kurangnya referensi yang dimiliki, kurangnya pemanfaatan media elektronik terutama aplikasi baik yang online maupun aplikasi yang bersifat offline yang sesuai dengan era revolusi industri 4.0. Salah satu aplikasi yang sesuai dengan era sekarang yakni flip bookmaker dalam pembelajaran. Oleh karena itu penelitian ini ingin melihat bagaimana peningkatan kemampuan literasi baca tulis dan numerasi. Jenis penelitian ini merupakan penelitian kuantitatif. Perolehan data penelitian melalui pre tes dan post tes. Data hasil tersebut di dengan menggunakan rumus presentasi untuk melihat sejauh mana peningkatan kemampuan literasi mahasiswa. Selanjutnya sebagai data tambahan yaitu wawancara dan dokumentasi. Pada penelitian ini melibatkan 2 mahasiswa untuk membantu peneliti sampai dengan publikasi pada jurnal. Metode penelitian ini adalah Kuantitatif dan jenis penelitian Quasi Eksperimen dengan desain penelitian One Group Pretest-Post-test design. Teknik analisis yang digunakan adalah analisis statistik deskriptif dan analisis statistik inferensial. Hasil penelitian menunjukkan bahwa flip bookmaker dalam meningkatkan kemampuan literasi numerasi. Hal tersebut membuktikan bahwa dengan memberikan rangsangan berupa media flip bookmaker dapat membangkitkan minat dan antusias mahasiswa dalam pembelajaran sehingga meningkatkan kemampuan literasi numerasi mahasiswa.
Perubahan Luasan Manggrove Menggunakan Data Citra Satelit di Distrik Manokwari Selatan Kabupaten Manokwari
Authors: Irnawati Irnawati , Milangoni Elok , Febriadi Ihsan , Soekamto Mira Herawati
Published: June 2024

Mangroves are one of the defining characteristics of transitional plants between the sea, water bodies, and land. They are only found in tropical and subtropical regions with some extreme conditions such as high salt content, high temperatures, high waves, sedimentation, and mud. The distribution of mangroves in Indonesia with the highest dense cover is in Papua Province with a total area of ​​1,084,514 hectares, and West Papua Province has mangrove forests with a total area of ​​483,800 hectares, 76% of which are primary mangrove forests and the rest are secondary mangrove forests (24%). One method to determine changes in the area of ​​mangrove vegetation is remote sensing technology aimed at identifying changes in the mangrove area covered by the mangrove ecosystem over different periods as potential forest resources using Composite image software ER Mapper series 6.4. Research results During the period 2014 - 2023, there has been a change in the area of ​​mangroves in South Manokwari District with a degraded mangrove forest area of ​​53,767 hectares, with a deforestation area of ​​5,974 hectares per year. In the same period, forest degradation of 43,442 hectares also occurred with a degradation area per year of 4,827 hectares. The accuracy level value of Landsat satellite image classification for changes in mangrove area in South Manokwari District, Manokwari Regency in 2014, 2017, 2020, and 2023 reached 92.5%, which means it is quite accurate
The Application of the Use of Indonesian Language in Promoting Tourist Destinations to ArchipelagoTourists in North Toraja Regency
Authors: Ernawati AB  , Syamsul Bahri  , St. Aminah AB  , Darmayasa
Published: June 2024

Indonesian language should be encouraged through tourism promotion, especially in the tourism sector, to describe the form of tourism promotion and implementation. Bahasa Indonesia, as a domestic tourism promotion, also describes the role of Bahasa Indonesia as tourism communication to develop and internationalise Bahasa Indonesia in the Department of Tourism and Cultural of North Toraja Regency. This research aims to describe the tourism promotion form in the Department of Tourism and Cultural of North Toraja Regency. Data collection techniques with in-depth interviews through the Snowball Sampling technique for the stakeholder included the private management of tourism attractions, tour guide, and visitors at tourist destination areas. The conclusion of this research is the promotional language to use in the Department of Tourism and Cultural of North Toraja Regency through two options of language: Bahasa Indonesia and English language, but also uses a traditional or local vocabulary which is often used for tourist attraction and describe the local language.
The Demotic Impulse of the Kitchen-Sink Dramas
Authors: Mello Cecília
Published: June 2024

In this article, I suggest a historical and theoretical re-evaluation of the British New Wave from the point of view of its demotic impulse. I begin by situating the kitchen-sink films within a broader framework of post-war innovation, driven by an aspiration to realism that reinvigorated British cinema and television within a novel historical conjuncture. I then investigate the specificity of British New Wave’s realism – with an emphasis on the films Saturday Night and Sunday Morning and A Taste of Honey – and consider their contribution to the development of an indigenous aesthetic, characterised by a demotic impulse. The relevance of the notion of demotic in the post-war cultural panorama can be attributed to the ‘equalising’ powers of the Second World War. As I will suggest, a prolific parallel can be established with another moment of historical transition during what Eric Hobsbawm called ‘the age of revolution’, in which the spirit of egalitarianism equally lay at the root of the search for a demotic. Here, I will focus on William Wordsworth’s poetic revolution to investigate the notions of egalitarianism and of demotic, which I believe can further our understanding of post-war realism in the British audio-visual landscape.
Writing the British New Wave: David Storey and This Sporting Life
Authors: Forrest David
Published: June 2024

This article dislodges the assumptions of authorial cohesiveness and centrality that have defined the scholarly and critical reception of the New Wave and suggests ways of reframing our understanding of British realism and the collaborative labours that underpin it. It does so through consideration of This Sporting Life, the adaptation of David Storey’s 1960 novel of the same name, which concerns the rise and fall of miner and rugby league player Frank Machin and his doomed relationship with his landlady, Mrs Hammond. Drawing primarily on Storey’s archive, held at the University of York, this article considers the role of the writer in shaping the film, and by extension, the hugely significant but often less heralded contribution made by writers to the ethos and aesthetics of the British New Wave.
Vägar till rättvis omställning: energigemenskaper i skärningspunkten mellan systemoptimering och demokratiskt deltagande
Authors: Envall Fredrik , Andersson Daniel
Published: June 2024

ENERGI HAR UNDER de senaste åren genomgått en förändring som samhällsfråga. Med raketfart har det gått från att vara en specialiserad domän för experter till en allmängiltig angelägenhet som flitigt omskrivs i dagspress. I synnerhet har det blivit tydligt att energi inbegriper mer än teknik. Debatterna om elkris, energisäkerhet, och elsystemets robusthet som följt i svallvågorna av Rysslands invasion av Ukraina är exempel på hur tekniken är tätt sammantvinnad med frågor av i högsta grad politisk och social karaktär. Den svåröverblickbara europeiska energimarknaden har också hamnat under luppi samband med dessa geopolitiska förändringar, inte minst eftersom en avkonsekvenserna har varit kraftigt stigande energipriser
Forskningsbaserad kunskap som redskap för undervisningsutveckling
Authors: Lunde Torodd , Höst Gunnar
Published: June 2024

Reflektioner från praktiken är en texttyp där lärares hantering av didaktiska utmaningar i den egna undervisningen står i centrum. Syftet med texttypen är att lärare ska kunna få möjlighet att dela med sig av vetenskapligt grundade reflektioner om hur den egna praktiken kan utvecklas. Men vad innebär det att reflektionerna är vetenskapligt grundade? Ett sätt att se på det är att didaktiska kunskaper och andra användbara forskningsresultat används som redskap för att adressera didaktiska utmaningar med syftet att göra undervisningen mer framgångsrik. I artikeln ger vi exempel på lärare som gjort detta och hur de kommunicerat sina erfarenheter.
A three-dimensional tissue-engineered rostral migratory stream as an in vitro platform for subventricular zone-derived cell migration
Authors: Purvis Erin M. , Garcia-Epelboim Andrés D. , Krizman Elizabeth N. , O’Donnell John C. , Cullen D. Kacy
Published: June 2024

In the brains of most adult mammals, neural precursor cells (NPCs) from the subventricular zone (SVZ) migrate through the rostral migratory stream (RMS) to replace olfactory bulb interneurons. Following brain injury, published studies have shown that NPCs can divert from the SVZ-RMS-OB route and migrate toward injured brain regions, but the quantity of arriving cells, the lack of survival and terminal differentiation of neuroblasts into neurons, and their limited capacity to re-connect into circuitry are insufficient to promote functional recovery in the absence of therapeutic intervention. Our lab has fabricated a biomimetic tissue-engineered rostral migratory stream (TE-RMS) that replicates some notable structural and functional components of the endogenous rat RMS. Based on the design attributes for the TE-RMS platform, it may serve as a regenerative medicine strategy to facilitate sustained neuronal replacement into an injured brain region or an in vitro tool to investigate cell-cell communication and neuroblast migration. Previous work has demonstrated that the TE-RMS replicates the basic structure, unique nuclear shape, cytoskeletal arrangement, and surface protein expression of the endogenous rat RMS. Here, we developed an enhanced TE-RMS fabrication method in hydrogel microchannels that allowed more robust and high-throughput TE-RMS assembly. We report unique astrocyte behavior, including astrocyte bundling into the TE-RMS, the presence of multiple TE-RMS bundles, and observations of discontinuities in TE-RMS bundles, when microtissues are fabricated in agarose microchannels containing different critical curved or straight geometric features. We also demonstrate that we can harvest NPCs from the SVZ of adult rat brains and that EGFP+ cells migrate in chain formation from SVZ neurospheres through the TE-RMS in vitro. Overall, the TE-RMS can be utilized as an in vitro platform to investigate the pivotal cell-cell signaling mechanisms underlying the synergy of molecular cues involved in immature neuronal migration and differentiation.
Unraveling the intricate relationship between lipid metabolism and oncogenic signaling pathways
Authors: Khan Fahad , Elsori Deena , Verma Meenakshi , Pandey Shivam , Obaidur Rab Safia , Siddiqui Samra , Alabdallah Nadiyah M. , Saeed Mohd , Pandey Pratibha
Published: June 2024

Lipids, the primary constituents of the cell membrane, play essential roles in nearly all cellular functions, such as cell-cell recognition, signaling transduction, and energy provision. Lipid metabolism is necessary for the maintenance of life since it regulates the balance between the processes of synthesis and breakdown. Increasing evidence suggests that cancer cells exhibit abnormal lipid metabolism, significantly affecting their malignant characteristics, including self-renewal, differentiation, invasion, metastasis, and drug sensitivity and resistance. Prominent oncogenic signaling pathways that modulate metabolic gene expression and elevate metabolic enzyme activity include phosphoinositide 3-kinase (PI3K)/AKT, MAPK, NF-kB, Wnt, Notch, and Hippo pathway. Conversely, when metabolic processes are not regulated, they can lead to malfunctions in cellular signal transduction pathways. This, in turn, enables uncontrolled cancer cell growth by providing the necessary energy, building blocks, and redox potentials. Therefore, targeting lipid metabolism-associated oncogenic signaling pathways could be an effective therapeutic approach to decrease cancer incidence and promote survival. This review sheds light on the interactions between lipid reprogramming and signaling pathways in cancer. Exploring lipid metabolism as a target could provide a promising approach for creating anticancer treatments by identifying metabolic inhibitors. Additionally, we have also provided an overview of the drugs targeting lipid metabolism in cancer in this review.
Influence of anionic species on the low temperature pyrolysis performance of heated tobacco sheets catalyzed by sodium salts
Authors: Zhao Xuebin , Wang Qiuling , Ai Dan , Tian Haiying , Zhang Zhan , Cao Ke , Wang Yixuan , Qi Wei , Li Bo , Niu Yapeng , Meng Lingchuang , Gao Beibei , Li Bin
Published: June 2024

Development of low temperature catalytic pyrolysis technology for heated tobacco sheets is expected to increase the aroma of heated tobacco products and improve their overall smoking quality. In this study, the low temperature pyrolysis performances of heated tobacco sheets catalyzed by various anionic sodium salts were investigated using TG-DTG, Py-GC-MS technology and smoke routine chemical composition analysis. The results showed that the total weight loss between 100°C and 300°C increased by 7.8%–13.15% after adding various anionic sodium salts, among which, sodium acetate and sodium tartrate showed a relatively higher weight loss. The relative content of free hydroxyacetone, furfuryl alcohol, butyrolactone and megastigmatrienone in the pyrolysis gas increased, while the relative content of free nicotine decreased. With the change of anionic species, the catalytic decomposition ability of cellulose, lignin, and other substances may change, resulting in the distribution alteration of compounds in the pyrolysis gas. After adding sodium acetate and sodium citrate, the release of total particulate matter (TPM), glycerol, and nicotine in flue gas increased. Overall, the addition of sodium acetate and sodium citrate showed a higher low temperature pyrolysis performance of heated tobacco sheets. The research results in this paper provide data support for changing the low temperature catalytic pyrolysis performance of heated tobacco sheets by adjusting the type of anions in sodium salts.
Prompt engineering for digital mental health: a short review
Authors: Priyadarshana Y. H. P. P. , Senanayake Ashala , Liang Zilu , Piumarta Ian
Published: June 2024

Prompt engineering, the process of arranging input or prompts given to a large language model to guide it in producing desired outputs, is an emerging field of research that shapes how these models understand tasks, process information, and generate responses in a wide range of natural language processing (NLP) applications. Digital mental health, on the other hand, is becoming increasingly important for several reasons including early detection and intervention, and to mitigate limited availability of highly skilled medical staff for clinical diagnosis. This short review outlines the latest advances in prompt engineering in the field of NLP for digital mental health. To our knowledge, this review is the first attempt to discuss the latest prompt engineering types, methods, and tasks that are used in digital mental health applications. We discuss three types of digital mental health tasks: classification, generation, and question answering. To conclude, we discuss the challenges, limitations, ethical considerations, and future directions in prompt engineering for digital mental health. We believe that this short review contributes a useful point of departure for future research in prompt engineering for digital mental health.
Engineering education challenges and strengths: reflecting on key-stakeholder's perspectives
Authors: Ferreira Carla , Gabriel Bárbara , Valente Robertt , Figueiredo Cláudia
Published: June 2024

We live in a society in constant scientific and technological change, where engineering education is required to develop the competences needed for future engineers to be able to respond to the complex and interdisciplinary problems that arise from this. It is no longer enough just to provide updated scientific and technological training to students, but it is also required to articulate the needs of society with the design of the curriculum and the expectations of the different stakeholders. The present paper's goal is to present the perceptions about engineering education through the lens of different institutional stakeholders, following a qualitative design study, through semi-structured interviews with seven key-stakeholders representing different scientific and professional institutions. These interviewees play an important role in the definition of guidelines for the engineering profession and in (re)thinking curricula reflecting the interaction with society, training and research. In this sense, it aims to explore the following objectives: (i) to know the perception about the profession, the profile of engineers and the engineering curricula; (ii) to identify the challenges posed to engineers in the job market and in society, today and in the future; and (iii) to reflect on a desirable profile to be attained by engineering students at the end of their Higher Education path. From the interviewees' perspective, competences development effectively involves learning approaches that realize which problem-solving strategies, concepts and capacities for social action should be developed in students, which are not restricted to disciplinary or specific content, but which allow (de)constructing curricula that reflect the different needs of society. In fact, as well as including the point of view of renowned international associations, this article reinforces the idea that the integration of science, technology, engineering and maths (STEM) into curricula is not only a challenge, but also a growing and inevitable phenomenon in response to society's needs. The curriculum, the competences to be privileged, the importance of interdisciplinarity, and the contribution of STEM and STEAM approaches from an integrated engineering perspective are interpreted as difficulties but also the target opportunities.
Developing a minifesta for effective academic-activist collaboration in the context of the climate emergency
Authors: McLaren Duncan P. , Anderson Christine , Barry John , Castán Broto Vanesa , de Cheveigné Suzanne , Chilvers Jason , Crowther Alison , Hupé Jean-Michel , Kalaugher Liz , Labussiere Olivier , Rothery Tina L. , Nadai Alain , Ortar Nathalie , Raine Jordan , Smith Graham , Wallenborn Grégoire , Walker Gordon
Published: June 2024

Justice-oriented climate activism is proliferating. Many scholars aspire to deliver research that supports activism. However, measures of impact for research evaluation and funding purposes place little weight on the use of research by activists. Here we consider how academics and academia might effectively support and enable climate activism. We report outcomes from a series of online deliberative workshops involving both activists and academics from several European countries. The workshops were facilitated to create space for discussion, sharing of experiences and the development of proposals for the future. The outcomes take the form of a set of principles (a “minifesta”) for academic-activist engagement generated by the group. In discussing the process and outputs, we argue that a focus on inclusion can support politically transformative change of the scale and urgency required. We suggest that this also demands a shift in attitudes toward the role of activism and activists in collaborative processes. We further discuss the inevitable incompleteness of this process, arguing that incompleteness is, itself, a feature of inclusive engagement. We conclude that scholars working on climate issues in any discipline could benefit from increasing mutually supportive collaboration with activists; and that such collaboration and inclusion could help liberate democracy from authoritarian tendencies and market influences. Collaborative engagements generate legitimate, rich, and impactful outcomes even with the limitations posed by COVID19. We, therefore, commend both the model of engagement and the principles it generated for our colleagues and peers.
Development and implementation of a rehabilitation triage algorithm for disasters in the subacute phase: an experience from the 2024 Noto peninsula earthquake
Authors: Shiota Shigehito , Orita Naoya , Tsubakita Yuma , Ichimoto Masaya , Shimada Noboru , Goto Naoya , Hirota Tomohiro , Taito Shunsuke , Hirata Kazuhiko , Mikami Yukio
Published: June 2024

Early rehabilitation during disasters such as earthquakes is an important but often undervalued responsibility of medical teams. Both the development of simple tools for assessing the life functioning of evacuees and the standardization of intervention methods are urgent issues in disaster rehabilitation. The Japanese Rehabilitation Assistance Team (JRAT), an officially recognized organization consisting of 10 suborganisations, was established after gaining important experience with disaster rehabilitation in the aftermath of the Great East Japan Earthquake. We, the Hiroshima JRAT, were dispatched to the Monzen area of Wajima City to support disaster recovery after the 2024 Noto Peninsula Earthquake. Since disaster rehabilitation assistance was not well established in the Monzen area of Wajima City, the medical team consulted JRAT for guidance on triaging evacuees based on their life functioning. We developed a rehabilitation triage algorithm that classifies evacuees into four triage tags based on their ability to perform three simple movements: sitting up, standing up from the floor, and one-leg standing. In our triage algorithm, an inability to sit up is classified as a red tag (difficulty living in a shelter without assistance), an inability to stand up from the floor is classified as a yellow tag (individual intervention: introduction of beds and handrails), one-leg standing for < 2 s is classified as a green tag (group intervention: installation of toilets and bath rails and use of walkers to prevent falls), and standing on one leg for more than 2 s is classified as a white tag (independent in ADLs). We worked with medical teams to triage 922 evacuees in 27 evacuation centers, resulting in the extraction of four red and eight yellow evacuees in 1 day. Our rehabilitation triage system has the potential to be a simple assessment tool for classifying the life functioning of disaster victims and linking them to appropriate supports.
Gluco-regulation & type 2 diabetes: entrenched misconceptions updated to new governing principles for gold standard management
Authors: Schwartz Stanley S. , Herman Mary E.
Published: June 2024

Our understanding of type 2 diabetes (T2D) has evolved dramatically. Advances have upended entrenched dogmas pertaining to the onset and progression of T2D, beliefs that have prevailed from the early era of diabetes research—and continue to populate our medical textbooks and continuing medical education materials. This review article highlights key insights that lend new governing principles for gold standard management of T2D. From the historical context upon which old beliefs arose to new findings, this article outlines evidence and perspectives on beta cell function, the underlying defects in glucoregulation, the remediable nature of T2D, and, the rationale supporting the shift to complication-centric prescribing. Practical approaches translate this rectified understanding of T2D into strategies that fill gaps in current management practices of prediabetes through late type 2 diabetes.
Optimal demand response scheduling and voltage reinforcement in distribution grids incorporating uncertainties of energy resources, placement of energy storages, and aggregated flexible loads
Authors: Zarei Alireza , Ghaffarzadeh Navid , Shahnia Farhad
Published: June 2024

Instead of expanding power plant capacities, which is an extremely expensive investment option, demand response offers an economical solution to the challenges arising from the variability and intermittency of the renewable energy resources and demand variations, particularly during demand peak periods. This paper proposes a multi-objective optimization framework for the optimal power flow problem that integrates a stepwise demand response involving flexible and aggregated loads. The process includes short-term demand forecasting using long short-term memory (LSTM) networks in a smart distribution grid, followed by the optimal allocation of energy storage systems, and load aggregators. By determining the optimal solution point of the multi-objective problem analytically, significant system costs and peak demand can be reduced without compromising system stability. Through numerical studies for a sample study case, a reduction of 22% in system costs, 2% in total voltage variation, and 10% in peak demand is observed for a negligible impact on customers’ convenience.
The influence and mechanism exploration of hydration environment on the stability of natural clay crude oil emulsion
Authors: Zhang Shusong , Liu Tianyu , Chen Qingyuan , Xiao Bao , Xian Xiaokang , Ye Zhongbin
Published: June 2024

The study investigated the effects and mechanisms of clay content, emulsion water content, pH, and metal cations on clay-crude oil emulsions. The results indicate the following: 1) At a water content of 50 V/V%, montmorillonite can form emulsions with crude oil at different concentrations, with the highest stability observed at 5 wt% content. In contrast, chlorite, illite, and kaolinite cannot form emulsions at low concentrations. 2) Under acidic conditions, montmorillonite, illite, and chlorite cannot form emulsions with crude oil, or the emulsions are highly unstable. However, kaolinite forms more stable emulsions under acidic conditions. In alkaline environments, emulsions formed by all clay minerals exhibit increased stability. 3) The order of the effectiveness of different metal cations in reducing the stability of montmorillonite-crude oil emulsions is K+ > Na+ > Mg2+ > Ca2+, while for chlorite, illite, and kaolinite, it is Mg2+ > Ca2+ > K+ > Na+. 4) The factors that influence the stability of clay-crude oil emulsions are the arrangement of clay particles in water and the dispersion capability of clay particles in water. The most significant influencing factor is the arrangement of clay particles in water.
Drone-based early detection of bark beetle infested spruce trees differs in endemic and epidemic populations
Authors: Bozzini Aurora , Brugnaro Stefano , Morgante Giuseppe , Santoiemma Giacomo , Deganutti Luca , Finozzi Valerio , Battisti Andrea , Faccoli Massimo
Published: June 2024

Introduction

European forests face increasing threats due to climate change-induced stressors, which create the perfect conditions for bark beetle outbreaks. The most important spruce forest pest in Europe is the European Spruce Bark Beetle (Ips typographus L.). Effective management of I. typographus outbreaks necessitates the timely detection of recently attacked spruce trees, which is challenging given the difficulty in spotting symptoms on infested tree crowns. Bark beetle population density is one of many factors that can affect infestation rate and symptoms development. This study compares the appearance of early symptoms in endemic and epidemic bark beetle populations using highresolution Unmanned Aerial Vehicles (UAV) multispectral imagery.

Methods

In spring of 2022, host colonization by bark beetles was induced on groups of spruce trees growing in 10 sites in the Southern Alps, characterized by different population density (5 epidemic and 5 endemic). A multispectral sensor mounted on a drone captured images once every 2 weeks, from May to August 2022. The analyses of a set of vegetational indices allowed the actual infested trees’ reflectance features and symptoms appearance to be observed at each site, comparing them with those of unattacked trees.

Results

Results show that high bark beetles population density triggers a more rapid and intense response regarding the emergence of symptoms. Infested trees were detected at least 1 month before symptoms became evident to the human eye (red phase) in epidemic sites, while this was not possible in endemic sites. Key performing vegetation indices included NDVI (Normalized Difference Vegetation Index), SAVI (Soil Adjust Vegetation Index, with a correction factor of 0.44), and NDRE (Normalized Difference Red Edge index).

Discussion

This early-detection approach could allow automatic diagnosis of bark beetles’ infestations and provide useful guidance for the management of areas suffering pest outbreaks.
Clinical profiles and molecular genetic analyses of 98 Chinese children with short statures
Authors: Fang Danfeng , Li Xing , Zhang Zhigang , Cai Hefei , Wang Lu , Yu Jiahe , Hu Xuanye , Ye Bin
Published: June 2024

Background

Short stature is one of the most prevalent endocrine disorders in children, and its genetic basis is a complex and actively researched subject. Currently, there is limited genetic research on exome sequencing for short stature, and more large-scale studies are necessary for further exploration.

Methods

The retrospective study entailed investigation of 98 Chinese children with short statures (height SDS ≤ −2.5) of unknown etiologies recruited between 2017 and 2021. Whole-exome sequencing (WES) was performed on these patients to identify the potential genetic etiologies. The clinical data were reviewed retrospectively to assess the pathogenicity of the identified mutations. Additionally, 31 patients consented to and received recombinant human growth hormone (rhGH) therapy for 12 months. The short-term effects of rhGH treatment were evaluated across different etiologies of patients with short statures.

Results

The WES results were used to identify 31 different variants in 18 genes among 24 (24.5%) patients. Individuals with more severe short statures were more likely to have underlying genetic etiologies. Short stature accompanied by other phenotypes had significantly higher diagnostic yields than simple severe short stature. The rhGH therapy demonstrated efficacy in most children. Nevertheless, the treatment response was suboptimal in a boy diagnosed with 3M syndrome.

Conclusion

WES is an important approach for confirming genetic disorders in patients with severe short statures of unknown etiologies, suggesting that it could be used as a primary diagnostic strategy. The administration of rhGH may not be suitable for all children with short statures, and the identification of the genetic cause of short stature by WES has significant guidance value for rhGH treatment.
Complement-Coagulation Cross-talk: Factor H-mediated regulation of the Complement Classical Pathway activation by fibrin clots
Authors: Kang Yu-Hoi , Varghese Praveen M. , Aiyan Ahmad Al , Pondman Kirsten , Kishore Uday , Sim Robert B.
Published: June 2024

The classical pathway of the complement system is activated by the binding of C1q in the C1 complex to the target activator, including immune complexes. Factor H is regarded as the key downregulatory protein of the complement alternative pathway. However, both C1q and factor H bind to target surfaces via charge distribution patterns. For a few targets, C1q and factor H compete for binding to common or overlapping sites. Factor H, therefore, can effectively regulate the classical pathway activation through such targets, in addition to its previously characterized role in the alternative pathway. Both C1q and factor H are known to recognize foreign or altered-self materials, e.g., bacteria, viruses, and apoptotic/necrotic cells. Clots, formed by the coagulation system, are an example of altered self. Factor H is present abundantly in platelets and is a well-known substrate for FXIIIa. Here, we investigated whether clots activate the complement classical pathway and whether this is regulated by factor H. We show here that both C1q and factor H bind to the fibrin formed in microtiter plates and the fibrin clots formed under in vitro physiological conditions. Both C1q and factor H become covalently bound to fibrin clots, and this is mediated via FXIIIa. We also show that fibrin clots activate the classical pathway of complement, as demonstrated by C4 consumption and membrane attack complex detection assays. Thus, factor H downregulates the activation of the classical pathway induced by fibrin clots. These results elucidate the intricate molecular mechanisms through which the complement and coagulation pathways intersect and have regulatory consequences.
Effectiveness of PD-1 inhibitor-based first-line therapy in Chinese patients with metastatic gastric cancer: a retrospective real-world study
Authors: Duan Yichun , Li Jielang , Zhou Shuang , Bi Feng
Published: June 2024

Objective

Programmed cell death protein-1 (PD-1) inhibitor-based therapy has demonstrated promising results in metastatic gastric cancer (MGC). However, the previous researches are mostly clinical trials and have reached various conclusions. Our objective is to investigate the efficacy of PD-1 inhibitor-based treatment as first-line therapy for MGC, utilizing real-world data from China, and further analyze predictive biomarkers for efficacy.

Methods

This retrospective study comprised 105 patients diagnosed with MGC who underwent various PD-1 inhibitor-based treatments as first-line therapy at West China Hospital of Sichuan University from January 2018 to December 2022. Patient characteristics, treatment regimens, and tumor responses were extracted. We also conducted univariate and multivariate analyses to assess the relationship between clinical features and treatment outcomes. Additionally, we evaluated the predictive efficacy of several commonly used biomarkers for PD-1 inhibitor treatments.

Results

Overall, after 28.0 months of follow-up among the 105 patients included in our study, the objective response rate (ORR) was 30.5%, and the disease control rate (DCR) was 89.5% post-treatment, with two individuals (1.9%) achieving complete response (CR). The median progression-free survival (mPFS) was 9.0 months, and the median overall survival (mOS) was 22.0 months. According to both univariate and multivariate analyses, favorable OS was associated with patients having Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1. Additionally, normal baseline levels of carcinoembryonic antigen (CEA), as well as the combination of PD-1 inhibitors with chemotherapy and trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive MGC, independently predicted longer PFS and OS. However, microsatellite instability/mismatch repair (MSI/MMR) status and Epstein-Barr virus (EBV) infection status were not significantly correlated with PFS or OS extension.

Conclusion

As the first-line treatment, PD-1 inhibitors, either as monotherapy or in combination therapy, are promising to prolong survival for patients with metastatic gastric cancer. Additionally, baseline level of CEA is a potential predictive biomarker for identifying patients mostly responsive to PD-1 inhibitors.
The impact of COVID-19 on “biological aging”
Authors: Humaira Amanullah Fathima , Alam Tanvir , El Hajj Nady , Bejaoui Yosra
Published: June 2024

The global impact of the SARS-CoV-2 pandemic has been unprecedented, posing a significant public health challenge. Chronological age has been identified as a key determinant for severe outcomes associated with SARS-CoV-2 infection. Epigenetic age acceleration has previously been observed in various diseases including human immunodeficiency virus (HIV), Cytomegalovirus (CMV), cardiovascular diseases, and cancer. However, a comprehensive review of this topic is still missing in the field. In this review, we explore and summarize the research work focusing on biological aging markers, i.e., epigenetic age and telomere attrition in COVID-19 patients. From the reviewed articles, we identified a consistent pattern of epigenetic age dysregulation and shortened telomere length, revealing the impact of COVID-19 on epigenetic aging and telomere attrition.
TRIM21 and Fc-engineered antibodies: decoding its complex antibody binding mode with implications for viral neutralization
Authors: Reusch Johannes , Franken Linda Elise , Then Jakob , Ringler Philippe , Butzer Joachim , Juroschek Thomas , Klein Christian , Schlothauer Tilman , Larivière Laurent
Published: June 2024

TRIM21 is a pivotal effector in the immune system, orchestrating antibody-mediated responses and modulating immune signaling. In this comprehensive study, we focus on the interaction of TRIM21 with Fc engineered antibodies and subsequent implications for viral neutralization. Through a series of analytical techniques, including biosensor assays, mass photometry, and electron microscopy, along with structure predictions, we unravel the intricate mechanisms governing the interplay between TRIM21 and antibodies. Our investigations reveal that the TRIM21 capacity to recognize, bind, and facilitate the proteasomal degradation of antibody-coated viruses is critically dependent on the affinity and avidity interplay of its interactions with antibody Fc regions. We suggest a novel binding mechanism, where TRIM21 binding to one Fc site results in the detachment of PRYSPRY from the coiled-coil domain, enhancing mobility due to its flexible linker, thereby facilitating the engagement of the second site, resulting in avidity due to bivalent engagement. These findings shed light on the dual role of TRIM21 in antiviral immunity, both in recognizing and directing viruses for intracellular degradation, and demonstrate its potential for therapeutic exploitation. The study advances our understanding of intracellular immune responses and opens new avenues for the development of antiviral strategies and innovation in tailored effector functions designed to leverage TRIM21s unique binding mode.
Identification of drug targets for Sjögren’s syndrome: multi-omics Mendelian randomization and colocalization analyses
Authors: Bai Yingjie , Wang Jiayi , Feng Xuefeng , Xie Le , Qin Shengao , Ma Guowu , Zhang Fan
Published: June 2024

Background

Targeted therapy for Sjögren’s syndrome (SS) has become an important focus for clinicians. Multi-omics-wide Mendelian randomization (MR) analyses have provided new ideas for identifying potential drug targets.

Methods

We conducted summary-data-based Mendelian randomization (SMR) analysis to evaluate therapeutic targets associated with SS by integrating DNA methylation, gene expression and protein quantitative trait loci (mQTL, eQTL, and pQTL, respectively). Genetic associations with SS were derived from the FinnGen study (discovery) and the GWAS catalog (replication). Colocalization analyses were employed to determine whether two potentially relevant phenotypes share the same genetic factors in a given region. Moreover, to delve deeper into potential regulation among DNA methylation, gene expression, and protein abundance, we conducted MR analysis to explore the causal relationship between candidate gene methylation and expression, as well as between gene expression and protein abundance. Drug prediction and molecular docking were further employed to validate the pharmacological activity of the candidate drug targets.

Results

Upon integrating the multi-omics data, we identified three genes associated with SS risk: TNFAIP3, BTN3A1, and PLAU. The methylation of cg22068371 in BTN3A1 was positively associated with protein levels, consistent with the negative effect of cg22068371 methylation on the risk of SS. Additionally, positive correlations were observed between the gene methylation of PLAU (cg04939496) and expression, as well as between expression and protein levels. This consistency elucidates the promotional effects of PLAU on SS risk at the DNA methylation, gene expression, and protein levels. At the protein level, genetically predicted TNFAIP3 (OR 2.47, 95% CI 1.56–3.92) was positively associated with SS risk, while BTN3A1 (OR 2.96E-03, 95% CI 2.63E-04–3.33E-02) was negatively associated with SS risk. Molecular docking showed stable binding for candidate drugs and target proteins.

Conclusion

Our study reveals promising therapeutic targets for the treatment of SS, providing valuable insights into targeted therapy for SS. However, further validation through future experiments is warranted.
Interruption of anti-thymocyte globuline treatment in solid organ transplantation is effectively monitored through a low total lymphocyte count
Authors: Rasander Rikke Olund , Sørensen Søren Schwartz , Krohn Paul Suno , Bruunsgaard Helle
Published: June 2024

Introduction

Anti-Thymocyte Globulin (ATG) is a cornerstone in immune suppression for solid organ transplantation. The treatment is a delicate balance between complications arising from over-immunosuppression such as infections and cancer versus rejection stemming from under-immunosuppression. CD3+ T-lymphocyte measurements are frequently employed for treatment monitoring. However, this analysis is costly and not always accessible. The aim of this study was to investigate whether the total count of lymphocytes could replace CD3+ T-lymphocyte measurements based on data from our transplantation center combined with a review of the literature. The hypothesis was that the total lymphocyte count could serve as a diagnostic surrogate marker for CD3+ T-lymphocytes.

Methods

A retrospective cohort study was conducted, including patients who underwent kidney and/or a pancreas transplantation and received ATG as induction therapy or for rejection treatment. The inclusion criterium was that the total lymphocyte count and CD3+ T-lymphocyte measurements were measured simultaneously on the same day. Additionally, PubMed and Embase were searched up to 18/10/2023 for published studies on solid organ transplantation, ATG, T-lymphocytes, lymphocyte count, and monitoring. In the retrospective cohort study, a total of 91 patients transplanted between 2016 and 2023, with 487 samples, were included.

Results

Total lymphocyte counts below 0.3 x 109/L had a high sensitivity (86%) as a surrogate marker of CD3+ T-lymphocytes below 0.05 x 109/L, but the specificity was low (52%) for total lymphocyte counts above 0.3 x 109/L as a surrogate marker for CD3+ T-lymphocytes above 0.05 x 109/L. A review of the literature identified seven studies comparing total lymphocyte counts and CD3+ T-lymphocytes in ATG monitoring. These studies supported the use of a low total lymphocyte count as a surrogate marker for CD3+ T-lymphocytes and an indicator to omit ATG treatment. However, there was no consensus regarding high total lymphocyte counts as an indicator for continued treatment.

Discussion

Results supports that the total lymphocyte count can be used to omit ATG treatment when below 0.3 x 109/L whereas the CD3+ T-lymphocyte analysis should be reserved for higher total lymphocyte counts to avoid ATG overtreatment.
The complement regulatory protein CD46 serves as a novel biomarker for cervical cancer diagnosis and prognosis evaluation
Authors: Yu Jun-Hui , Yuan Hao-Bo , Yan Zi-Yi , Zhang Xia , Xu Hui-Hui
Published: June 2024

Background

CD46 has been revealed to be a key factor in malignant transformation and cancer treatment. However, the clinical significance of CD46 in cervical cancer remains unclear, and this study aimed to evaluate its role in cervical cancer diagnosis and prognosis evaluation.

Methods

A total of 180 patients with an initial diagnosis of cervical cancer were enrolled at Taizhou Hospital of Zhejiang Province, China. The plasma levels of soluble CD46 (sCD46) and the expression of membrane-bound CD46 (mCD46) were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), respectively.

Results

CD46 was found to be significantly upregulated in cervical cancer tissues vs. normal tissues, while no CD46 staining was detected in paired adjacent noncancerous tissues. CD46 staining was more pronounced in cancer cells than in stromal cells in situ (in tissues). Moreover, the plasma levels of sCD46 were able to some extent discriminate between cancer patients and healthy women (AUC=0.6847, 95% CI:0.6152–0.7541). Analysis of Kaplan–Meier survival curves revealed that patients with low CD46 expression had slightly longer overall survival (OS) than patients with high CD46 expression in the tumor microenvironment, but no significant difference. Univariate Cox regression analysis revealed that CD46 (P=0.034) is an independent risk factor for OS in cervical cancer patients.

Conclusion

The present study demonstrated that cervical cancer patients exhibit aberrant expression of CD46, which is closely associated with a poor prognosis, suggesting that CD46 plays a key role in promoting cervical carcinogenesis and that CD46 could serve as a promising potential target for precision therapy for cervical cancer.