bluuebunny/crossref_metadata_2025 huggingface dataset:
PAPEL DA FAMÍLIA NO PROCESSO EDUCATIVO DA PRIMEIRA INFÂNCIA
Authors: Serpa Paulo Roberto , Silva Stefany Mendes da , Silva Margarete de Lima Mendes da
Published: August 2024

O tema desta pesquisa foi definido com base nas observações e vivências realizadas nos estágios curriculares de Educação Infantil e Gestão no âmbito do curso de graduação em Pedagogia de uma instituição particular de Ensino Superior do Litoral Catarinense. A presente pesquisa segue a abordagem qualitativa a partir da pesquisa bibliográfica (Gil, 1994), sendo para tanto realizada através da análise documental. Para construir o quadro teórico de referência utilizamos o Google Scholar e SciELO. Como método de análise foi adotada a análise descritiva e interpretativa a partir das experiências pessoas dos pesquisadores e dos achados da pesquisa (Stake, 2011). Questão-problema: Como a família pode influenciar no processo educativo da criança? Como hipótese, acreditamos que um núcleo familiar bem estruturado pode ser uma forte influência no processo formativo da criança, seja na vida pessoal, profissional ou escolar. Nesse contexto, o objetivo geral desta pesquisa é compreender a importância da participação da família na educação infantil.
RANCANG BANGUN SISTEM COMPUTER BASED TEST (CBT) BERBASIS WEBSITE PADA MIS GUPPI SAWANG LEBAR
Authors: Rizki Rey Babul , Oktoeberza Widhia KZ
Published: August 2024

Saat ini, MIS Guppi Sawang Lebar memiliki Laboratorium Komputer tetapi fasilitas tersebut tidak dapat dimanfaatkan dengan baik dan MIS Guppi Sawang Lebar ingin mengadakan ujian yang memanfaatkan computer guna sebagai simulasi ujian yang dilakukan melalui computer yang diadakan oleh pemerintah. Namun, MIS Guppi Sawang Lebar memiliki beberapa keterbatasan, seperti tidak adanya perangkat lunak yang mendukung untuk melakukan ujian melalui komputer. Maka akan dirancang dan dibangun Sistem Computer Based Test (CBT) pada MIS Guppi Sawang Lebar. Metode penelitian yang diterapkan adalah pengembangan sistem informasi berbasis web. Pengembangan ini menggunakan berbagai teknologi, termasuk HTML, PHP, Bootstrap, dan Laravel sebagai framework, serta MySQL sebagai manajemen database. Hasil dari pengembangan Sistem Computer Based Test (CBT) ini adalah pengguna memiliki akses ke fitur-fitur yang lengkap. Halaman admin memungkinkan untuk menambahkan pengguna, membuat daftar ujian, menetapkan sesi, dan melihat grafik nilai. Di sisi lain, halaman pengguna memungkinkan untuk melihat jadwal sesi ujian dan informasi tentang ujian yang akan dilakukan. Dengan adanya sistem tersebut, diharapkan dapat mempermudah MIS Guppi Sawang Lebar dalam proses ujian yang menggunakan computer.
Improving the efficiency of exponential ratio-type estimator for population median: A calibration weight adjustment approach
Authors: Iseh Mathew , Bassey Kufre
Published: August 2024

This paper modifies the Bahl and Tuteja exponential ratio-type estimator for population median under simple random and stratified sampling schemes using calibration
weight adjustment technique with supplementary information to vary the stratum
weights. The bias and mean square error of the modified estimator were obtained
up to the second-order approximation, which satisfies the necessary conditions for
efficiency. The findings show that the new estimator surpasses existing estimators in
efficiency gain. This suggests the appropriateness of calibration weight modification
in boosting the efficiency of a population parameter estimator under stratified random sampling especially where the population parameter of the auxiliary variable is
known and correlate with the variable of interest.
Bitcoin and South African Stock Market Returns during COVID-19 Pandemic: A test of the Safe-Haven Hypothesis
Authors: Udom Akaninyene , Nnamani Sopuru
Published: August 2024

This paper tests the safe-haven property of Bitcoin for South African stocks using Full and Diagonal BEKK-GARCH models. The study uses the Johannesburg stock exchange Top40 index, and bitcoin returns data before COVID-19 (August 2018 to December 2019) and during COVID-19 (January 2020 to June 2021). The results show that bitcoin cannot be considered as safe-haven for stocks in South Africa since it is weakly correlated with stock and had a high volatility during the Pandemic. Therefore, the safe-haven hypothesis of bitcoin on South African stocks is not true for the period under study. The policy implication is that bitcoin is not an appropriate safe-haven asset on South African stocks because it lacks store of value properties.
Financial Inclusion and Poverty Reduction in Nigeria: The Role of Microfinance Institutions
Authors: Ugwuoke Okwudili , Ogbonna Oliver , Freeman Aye-Agele
Published: August 2024

This study investigates the role of microfinance institutions as a vehicle for driving financial inclusion and alleviating poverty in Nigeria using the EFinA 2018 household survey data. The probit model, propensity score matching, and average treatment effect methods are applied for the analyses. The study finds that financial inclusion driven by access to, and usage of products/services provided by microfinance institutions reduces poverty. The study recommends among others the need for increased access to microfinance products/services and an integrated poverty reduction policies that identifies microfinance institutions as a critical enabler.
Generalized Ratio-Product cum Regression Variance Estimator in Two-Phase Sampling
Authors: Muhammad Isah
Published: August 2024

This study develops a flexible and efficient generalized ratio-product cum regression-type estimator of population variance utilizing auxiliary variable in two-phase sampling that incorporates the properties of ratio-type and product-type estimators. The properties of the estimator were derived using first order approximation. The theoretical conditions under which the precision and the flexibility of the estimator is better than some classical estimators are also provided. Empirical evidence from five real datasets suggests that the proposed estimator outperforms the classical variance, ratio variance, product, and exponential ratio type estimators in terms of precision and efficiency. The estimator can be utilized to provide better variance estimates for various phenomena such as inflation variation, exchange rate variation and standard of living variation for better policymaking.
PERANCANGAN APLIKASI INFORMASI PENDAKIAN GUNUNG DI INDONESIA BERBASIS ANDROID DENGAN MENGGUNAKAN METODE PROTOTYPE
Authors: Fauzi Aditya Ahmad , Adisuputra Adisuputra
Published: August 2024

Nowadays, more and more teenagers and adults are interested in mountain climbing. Climbers are keen to find information about the routes and mountains they will be climbing. However, many mountaineers complain that the information they get about climbing routes is not accurate or complete. The information currently available is only general information and does not have accurate data such as coordinate points, mountain profiles, transportation facilities, and other facilities that help climbing.  To solve this problem, Object Oriented Design (OOD) and Prototype system development methods were used to create an Android-based Indonesian mountaineering information application. The application was developed using Android Studio and designed to provide comprehensive information for mountaineers, including paths to the mountain, photo galleries, current news about the mountain to be climbed, climbing posts, and geographical locations. The study resulted in contributions in various aspects that can improve the safety and comfort of mountaineers in Indonesia. With more accurate and complete information and the utilization of modern technology, this application supports mountaineering activities significantly. Climbers not only get better guidance but also feel safer and more comfortable in pursuing their hobby.
SISTEM INFORMASI POS PELAYANAN TERPADU BERBASIS WEBSITE MENGGUNAKAN METODE EXTREME PROGRAMMING
Authors: Ermawati Erni , Indriyanti Indriyanti , Ichsan Nurul , Wahyuni Tri , Fatah Haerul
Published: August 2024

The problem in this research is that the technical notification of Posyandu schedules is still done verbally by word of mouth among the community and is also only announced via loudspeakers at local mosques. This method makes the dissemination of information related to the Posyandu schedule less effective. The main problem that often arises is that there are still parents who don't know the Posyandu schedule, there are even parents who forget the Posyandu schedule. The aim of this research is to make it easier for cadres to convey information and make it easier for parents to receive information about posyandu activity schedules via WhatsApp Blast. This research uses the Extreme Programming method which consists of 4 stages, namely planning, designing, coding and testing. Extreme Programming is a method that is considered effective in its application because it can produce a system that is fast and responsive to changing needs. The result of this research is a posyandu information system based on WhatsApp Blast which was created based on extreme programming stages. Functional testing using the Black Box method shows that the system has met expectations.
Towards optimal therapy intensity in pediatric acute lymphoblastic leukemia
Authors:   , Østergaard Anna
Published: August 2024

B-cell acute lymphoblastic leukemia (ALL) accounts for 25% of childhood cancer cases. Risk adapted treatment strategies have increased the 5-year survival rates from 0% in the 1960s to over 90% on recent trials. With the current high survival rates, possibilities for therapy reduction become an increasingly important topic. Although current trials do test de-escalation of several drugs, unconscious undertreatment might also be present. For further safe reduction of therapy, more knowledge is needed on how much therapy is needed to cure the disease and on biological factors associated with relapse. The aim of this thesis is to contribute to this knowledge by looking into several subgroup-specific challenges.

The research presented in this thesis shows that besides response to the first chemotherapy courses, the biology of leukemic and germline cytogenetic aberrations can affect treatment outcome. The survival rate of children with ALL with an ETV6::RUNX1 translocation is around 97%. This high survival rate asks for studies how to reduce therapy in this group of patients. We show that in ETV6::RUNX1 ALL different dosage schemes and dose intensities can lead to similar outcomes suggesting possibilities for treatment de-escalation. However, for safe treatment reduction more knowledge on relapse in ETV6::RUNX1 ALL specifically is needed. Therefore, we investigated the effect of IKZF1 deletions, a known poor prognostic factor in B-ALL, and found that they do not affect prognosis in ETV6::RUNX1 ALL. To explore the genetic landscape of relapse in ETV6::RUNX1 ALL further, we generated single cell genome wide copy number data to make an overview of the spectrum of (sub)clonal and co-occurring copy number alterations in ETV6:RUNX1 ALL experiencing relapse. This was of value in detecting (sub)clonal gains and losses larger than 1Mb in size, as well as genomic duplication thereby elucidating heterogeneity in copy number aberrant clones and patterns of relapse evolution in ETV6::RUNX1 ALL.

In contrast to ETV6::RUNX1 ALL, we found that when treating non-high risk ALL in patients with Down syndrome, due to differences in drug metabolism and resulting prescription behavior, unintentional treatment reduction might occur in this patient group. Differences in prescription behavior were also found in our study exploring the effect of socio-economic position on maintenance therapy. Although adherence to maintenance drugs did not differ, children in families with short parental education or unemployed parents were prescribed lower doses of maintenance therapy drugs by their physicians. Therefore, one should be cautious when reducing treatment intensity in these specific patient groups to maintain an effective therapy.

The great puzzle of safely reducing treatment to reduce side effects without endangering leukemia cure rates is unfortunately not yet solved. However, this thesis adds new insights needed to ultimately give all pediatric patients with B-ALL optimal treatment and an optimal quality of life.
Türkiye’yi Doğu ve Batı Kavramları Üzerinden Konumlandırmak: Kültürel Kodlar ve Formel Jeopolitik Söylemler
Authors: Öztürk Belçim , Özgen Nurettin
Published: August 2024

Bu çalışma, Türkiye’nin Doğu ve Batı arasında nasıl konumlan(dırıl)dığını, değişen jeopolitik yörüngesine dair tahayyüllere yönelik söylem ve anlatılara odaklanmaktadır. Spesifik olarak, Türkiye’de Doğu ve Batı kavramlarını inşa eden jeopolitik ve kültürel zihniyetin, nasıl bir Doğu-Batı tahayyülü yarattığını araştırmaktır. Türkiye’de Doğu ve Batı üzerine yapılan tartışmalar, tarihsel, politik ve kültürel geçmişi bagajında taşımakla beraber, güncel olay ve olgulara ilişkin söylemler üzerinde de söz sahibidir. Bu eğilim bazı dönemlerde değişmiş olsa da Türkiye coğrafyasına ilişkin tasvirlerin ontolojik kurulumu çoğunlukla Doğu ve Batı inşası üzerine kuruludur. Bu çalışma nitel araştırma desenine göre kurgulanmıştır. Çalışmanın örneklem grubunu, İstanbul Üniversitesi ve Van Yüzüncü Yıl Üniversitesi'nin İlahiyat, Edebiyat ve Siyasal Bilgiler/İktisadi ve İdari Bilimler Fakültelerinde öğrenim gören 240 katılımcı oluşturmaktadır. Elde edilen veriler MAXQDA paket programı aracılığıyla çözümlenmiştir. Analizler, Doğu ve Batı tahayyül biçimi ile politik söyleme konu olan jeopolitik tahayyüller arasında ilişki olduğunu göstermektedir.
Families' Orientation of Children towards Science and Children's Perception of Science
Authors: Bal Emine , Kaya Gökhan
Published: August 2024

This study aimed to examine the levels of families directing their children towards science and children's perception of science in a holistic framework. The research was conducted using mixed methods. Using criterion and convenience sampling methods, 168 parents with preschool children constituted the study group. The study group in the qualitative dimension of the research included 11 families with children between the ages of 3-6 and their children. Three different data collection tools were used in the study. A 5-point Likert-type, 18-item, 3-factor scale developed by Bal and Kaya (2022) was used as a quantitative data collection tool. As a qualitative data collection tool, a 6-question structured interview form developed by the researcher and drawings obtained from children were used. As a result of the study, it was determined that the level of families' orientation of children towards science differed significantly according to the variables of education level and child age, and the level of families' orientation of children towards science had a significant effect on children's perception of science.
PEMANFAATAN FOTO UDARA UNTUK RENCANA PENGEMBANGAN KAWASAN WISATA DESA TAMANSARI
Authors: Firmansyah Yudi
Published: August 2024

ABSTRAK Penyusunan rencana pengembangan suatu Kawasan sangat membutuhkan data dasar yang memiliki tingkat validitas serta tingkat presisi yang tinggi. Salahsatu data dasar yang dibutuhkan adalah peta citra resolusi tinggi, beberapa jenis peta citra resolusi tinggi telah lazim digunakan dalam berbagai analisis perencanaan. Untuk perencanaan Kawasan yang memiliki area tidak terlalu luas pemanfaatan foto udara sebagai data dasar dalam analisis perencanaan dinilai sangat efektif dan efisien dari segi kepraktisan metode dan biaya. Dalam penyusunan rencana pengembangan Kawasan wisata di Desa Tamansari memanfaatkan metode foto udara sebagai data dasar analisis. Pengambilan foto udara dilakukan dengan menggunakan pesawat tanpa awak atau drone dengan tipe DJI Mavic Pro 2. Dari hasil analisis yang dilakukan dari peta citra diketahui bahwa lokasi rencana pengembangan Kawasan wisata desa Tamansari memiliki luas 2,4Ha yang memiliku tutupan lahan dominan semak belukar dan vegetasi hutan serta berbatasan langsung dengan Kawasan Taman Nasional Gunung Halimun Salak. Data dasar tersebut menjadi pertimbangan dalam penentuan konsep rencana pengembangan pariwisata yang akan disusun.  Kata Kunci : Potret Udara, Pengembangan Wisata  ABSTRACT Preparing a development plan for an area really requires basic data that has a high level of validity and precision. One of the basic data needed is a high-resolution image map. Several types of high-resolution image maps are commonly used in various planning analyses. For planning areas that have areas that are not too large, the use of aerial photography as basic data in planning analysis is considered very effective and efficient in terms of method practicality and cost. In preparing the development plan for the tourist area in Tamansari Village, aerial photography methods were used as basic data analysis. Aerial photography was taken using an unmanned aircraft or drone with the DJI Mavic Pro 2 type. From the results of the analysis carried out on the image map, it is known that the location of the planned development of the Tamansari village tourist area has an area of 2.4 Ha which has dominant land cover of shrubs and forest vegetation. and directly borders the Mount Halimun Salak National Park Area. This basic data is taken into consideration in determining the concept of the tourism development plan that will be prepared. Keywords          : Aerial photography, Tourism Development
MODEL PENANGANAN RESIKO LONGSOR DI LERENG SUNGAI CILEBAKCAWI DESA MUARASARI KECAMATAN BOGOR SELATAN
Authors: Ismiralda Dinta Anindy , Hadi Singgih Irianto Trisilo , Widia Winda
Published: August 2024

Model penanganan resiko longsor pada lereng sungai dapat diawali dengan menghitung faktor keamanan lereng. Analisis faktor keamanan lereng didapat dengan menganalisis beberapa parameter material lereng dengan menggunakan program geo-slope. Parameter yang dibutuhkan adalah jenis material penyusun lereng dari hasil pemetaan geologi dan akusisi data geolistrik, sifat fisik dan mekanika tanah dari uji laboratorium, dan geometri lereng. Berdasarkan analisis faktor keamanan  lereng Sungai Cilebakcawi, kondisi lereng dalam keadaan labil dengan nilai faktor keamanannya 0,983. Angka keamanan lereng pada lokasi penelitian juga sangat dipenaruhi oleh kedalaman MAT. Dengan kondisi labil tersebut perlu dibangun perkuatan lereng diantaranya dengan penggunaan bronjong kawat yang dikombinasikan dengan terasering dan pile. Hasil dari kombinasi perkuatan ini dapat menaikan angka kemanan lereng menjadi diatas 3,328 walau dalam kondisi MAT dangkal yang menunjukan lereng dalam kondisi stabil atau mantap.Kata kunci :Penanganan Resiko Longsor, Faktor Keamanan Lereng, FK, Bronjong kawat, pile.ABSTRACTThe model for handling landslide risk on river slopes can be started by calculating the slope safety factor. Analysis of slope safety factoris obtained by analyzing several slope material parameters using the geo-slope program. The parameters required are the type of material that makes up the slope from the results of geological mapping and geoelectrical data acquisition, the physical and mechanical properties of the soil from laboratory tests, and the geometry of the slope. Based on an analysis of the safety factor for the slopes of the Cilebakcawi River, the condition of the slopes is in an unstable state with a safety factor value of 0.983. The slope safety score at the research location is also greatly influenced by the depth of the MAT. With these unstable conditions, it is necessary to strengthen the slopes, including using wire gabions combined with terracing and piles. The results of this strengthening combination can increase the slope safety figure to above 3.328 even in shallow MAT conditions, which indicates the slope is in a stable or stable condition.Keywords:Model for Handling landslide, Slope Safety Factor, FK, Wire Gabion, pile.
Rapid prediction of wall shear stress in stenosed coronary arteries based on deep learning
Authors: Alamir Salwa Husam , Tufaro Vincenzo , Trilli Matilde , Kitslaar Pieter , Mathur Anthony , Baumbach Andreas , Jacob Joseph , Bourantas Christos V. , Torii Ryo
Published: August 2024

There is increasing evidence that coronary artery wall shear stress (WSS) measurement provides useful prognostic information that allows prediction of adverse cardiovascular events. Computational Fluid Dynamics (CFD) has been extensively used in research to measure vessel physiology and examine the role of the local haemodynamic forces on the evolution of atherosclerosis. Nonetheless, CFD modelling remains computationally expensive and time-consuming, making its direct use in clinical practice inconvenient. A number of studies have investigated the use of deep learning (DL) approaches for fast WSS prediction. However, in these reports, patient data were limited and most of them used synthetic data generation methods for developing the training set. In this paper, we implement 2 approaches for synthetic data generation and combine their output with real patient data in order to train a DL model with a U-net architecture for prediction of WSS in the coronary arteries. The model achieved 6.03% Normalised Mean Absolute Error (NMAE) with inference taking only 0.35 s; making this solution time-efficient and clinically relevant.
Mine waste rock as a soil amendment for enhanced weathering, ecosystem services, and bioenergy production
Authors: Russell Mackenzie D. , Heckman Katherine A. , Pan Lei , Ye Xinyu , Zalesny Ronald S. , Kane Evan S.
Published: August 2024

Enhanced weathering of terrestrial rock material is a promising method for the removal of anthropogenic CO2 emissions from the atmosphere. Herein, we demonstrate that an ameliorated mining waste product can be effectively weathered in the soil environment when used as a soil amendment in conjunction with the cultivation of fast-growing willows (Salix matsudana Koidz. ⨯ S. alba L. “Austree”) in a pot study environment. Utilizing this locally sourced amendment minimizes emissions associated with grinding and transportation of enhanced weathering materials. Results showed that the willows were able to tolerate the relatively high metal concentrations of this amendment and sequester inorganic carbon (C) through the production of bicarbonate in soil solution. During the period of peak plant growth (10 weeks after planting), alkalinity measurements of soil solution from pots with willows and the addition of 25% by mass mine waste product indicated an additional 10 mg of inorganic C sequestration per liter of leached soil solution compared to unamended soils with willows. This represents 4.5 times the inorganic C sequestration rate of unamended soils. The addition of ameliorated mining waste also increased the pH of the soil solution by up to two units (pH of 6 in control vs. pH of 8 with the addition of 25% by mass mineral amendment). In addition to inorganic C sequestration, weathering of the ameliorated mining waste product may also provide base cations (such as calcium and magnesium) which could improve soil fertility. These results are encouraging for future investigation of ameliorated mine waste rock to sequester carbon and enhance the production of willows grown for ecosystem services and phytotechnologies.
Four novel variants identified in the ACADVL gene causing very-long-chain acyl-coenzyme A dehydrogenase deficiency in four unrelated Chinese families
Authors: Li Lulu , Tang Yue , Zhao Jinqi , Gong Lifei , Yang Nan , Wang Shunan , Yang Haihe , Kong Yuanyuan
Published: August 2024

Background: The biochemical and genetic characteristics of four very-long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) patients, clarifying their pathogenic genetic factors and evaluating the application value of genetic diagnosis in the early diagnosis of VLCADD, are reported and discussed in this article.

Methods: Patients underwent blood tandem mass spectrometry (MS/MS), urine gas chromatography (GC/MS), and high-throughput sequencing technology. New variants were analyzed for pathogenicity using bioinformatics software. Swiss-PdbViewer software was used to predict the effect of variants on the structure of the very-long-chain acyl-CoA dehydrogenase (VLCAD) protein.

Result: A total of four VLCADD patients were diagnosed. They revealed elevated levels of C14, C14:1, C14:2, C14:1/C2, C14:1/C10, and C14:1/C12:1. Two patients were early-onset neonatal cases and died during infancy and the neonatal period, respectively. Seven kinds of variants were detected, including four novel variants. Bioinformatics software revealed that the variants were harmful, and the Swiss-PdbViewer results suggest that variation affects protein conformation.

Conclusion: This study identified four novel ACADVL gene variants. These findings contribute to the understanding of the genetic basis and pathogenesis of VLCADD. Meanwhile, the study enriches the genetic mutation spectrum and the correlation between genotypes and phenotypes of VLCADD, indicating that genetic diagnosis plays an essential role in the early diagnosis and treatment of VLCADD.
Predictors of long-acting contraceptive utilization hot spots in Ethiopia: using geographical weighted regression analysis
Authors: Abate Hailemichael Kindie , Azagew Abere Woretaw , Kassahun Chanyalew Worku , Wassie Mulugeta , Mekonnen Chilot Kassa , Wassie Yilkal Abebaw , Zegeye Alebachew Ferede
Published: August 2024

Background

The use of long-acting contraceptives is a common health challenge in Ethiopia. Therefore, the current study aimed to assess the determinants of using long-acting contraceptive hot spots in Ethiopia using data from the Ethiopian Mini Demographic and Health Survey for 2019.

Methods

This study used data from the Ethiopia Mini Demographic and Health Survey 2019 and included a total weighted sample of 8,885 women in the analysis. The geographical variation of long-acting contraceptive usage was initially observed using hot spot analysis. Arc GIS version 10.7 was used for geographically weighted regression. Ordinarily, least squares regression was performed to identify predictors that explain the geographical variation in the use of long-acting contraceptives. Geographic weighted regression was used to predict the hot spot area of long-acting contraceptive methods.

Results

The overall prevalence of long-acting contraceptive utilization use was 6.9% (95% confidence interval: 6.4–7.45). Most of the statistically significant hot spots for long-acting contraceptives were found in lactated areas of the Oromia part of Amhara and Dire Dawa. Primary education, followers of the Muslim religion, marital status, and women with >4 children were the determinants of spatial variation use of hot spot areas for long-acting contraceptive methods.

Conclusions

A detailed map of long-acting contraceptive use hot spots and their determinants will enable decisions to target their sociodemographic-related predictors of women.
The JAK1/JAK2 inhibitor ruxolitinib inhibits mediator release from human basophils and mast cells
Authors: Poto Remo , Cristinziano Leonardo , Criscuolo Gjada , Strisciuglio Caterina , Palestra Francesco , Lagnese Gianluca , Di Salvatore Antonio , Marone Gianni , Spadaro Giuseppe , Loffredo Stefania , Varricchi Gilda
Published: August 2024

Introduction

The Janus kinase (JAK) family includes four cytoplasmic tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) constitutively bound to several cytokine receptors. JAKs phosphorylate downstream signal transducers and activators of transcription (STAT). JAK-STAT5 pathways play a critical role in basophil and mast cell activation. Previous studies have demonstrated that inhibitors of JAK-STAT pathway blocked the activation of mast cells and basophils.

Methods

In this study, we investigated the in vitro effects of ruxolitinib, a JAK1/2 inhibitor, on IgE- and IL-3-mediated release of mediators from human basophils, as well as substance P-induced mediator release from skin mast cells (HSMCs).

Results

Ruxolitinib concentration-dependently inhibited IgE-mediated release of preformed (histamine) and de novo synthesized mediators (leukotriene C4) from human basophils. Ruxolitinib also inhibited anti-IgE- and IL-3-mediated cytokine (IL-4 and IL-13) release from basophils, as well as the secretion of preformed mediators (histamine, tryptase, and chymase) from substance P-activated HSMCs.

Discussion

These results indicate that ruxolitinib, inhibiting the release of several mediators from human basophils and mast cells, is a potential candidate for the treatment of inflammatory disorders.
A bibliometric analysis of drug resistance in immunotherapy for breast cancer: trends, themes, and research focus
Authors: Zhang Rendong , Jiang Qiongzhi , Zhuang Zhemin , Zeng Huancheng , Li Yaochen
Published: August 2024

While breast cancer treatments have advanced significantly nowadays, yet metastatic, especially triple-negative breast cancer (TNBC), remains challenging with low survival. Cancer immunotherapy, a promising approach for HER2-positive and TNBC, still faces resistance hurdles. Recently, numerous studies have set their sights on the resistance of immunotherapy for breast cancer. Our study provides a thorough comprehension of the current research landscape, hotspots, and emerging breakthroughs in this critical area through a meticulous bibliometric analysis. As of March 26, 2024, a total of 1341 articles on immunology resistance in breast cancer have been gathered from Web of Science Core Collection, including 765 articles and 576 reviews. Bibliometrix, CiteSpace and VOSviewer software were utilized to examine publications and citations per year, prolific countries, contributive institutions, high-level journals and scholars, as well as highly cited articles, references and keywords. The research of immunotherapy resistance in breast cancer has witnessed a remarkable surge over the past seven years. The United States and China have made significant contributions, with Harvard Medical School being the most prolific institution and actively engaging in collaborations. The most contributive author is Curigliano, G from the European Institute of Oncology in Italy, while Wucherpfennig, K. W. from the Dana-Farber Cancer Institute in the USA, had the highest citations. Journals highly productive primarily focus on clinical, immunology and oncology research. Common keywords include “resistance”, “expression”, “tumor microenvironment”, “cancer”, “T cell”, “therapy”, “chemotherapy” and “cell”. Current research endeavors to unravel the mechanisms of immune resistance in breast cancer through the integration of bioinformatics, basic experiments, and clinical trials. Efforts are underway to develop strategies that improve the effectiveness of immunotherapy, including the exploration of combination therapies and advancements in drug delivery systems. Additionally, there is a strong focus on identifying novel biomarkers that can predict patient response to immunology. This study will provide researchers with an up-to-date overview of the present knowledge in drug resistance of immunology for breast cancer, serving as a valuable resource for informed decision-making and further research on innovative approaches to address immunotherapy resistance.
The role of platform margin collapses and slope landslides in the initiation and evolution of submarine canyons
Authors: Chen Junjin , Li Qi , Wu Shiguo , Liu Shiqiao
Published: August 2024

The Zhongsha Platform is the largest modern isolated carbonate platform of around 8600 km2 in the South China Sea, providing a unique case study for sedimentary processes in pure carbonate settings. High-resolution multibeam bathymetric data, two-dimensional seismic profiles, and surface sediment cores are utilizes to reveal the initiation and evolution of submarine canyons on the northeastern slope of the Zhongsha Platform. Three submarine canyons are revealed within the survey area that incise the slope at water depths between 600 and 4100 m. C1 presents a linear pattern, whereas C2 and C3 exhibit dendritic morphologies. A large-scale scalloped collapse has deeply excavated the platform margin and slope. Within this catastrophic failure, C2 originated in a northeastward orientation and subsequently converted to an eastward direction with a length of 54.8 km. It is distinguished by the erosion of numerous tributaries in the upper course, the transition of flow direction in the middle course, and the presence of retrogressive landslides in the lower course. Slope landslides extend eastward from middle-lower slope towards the oceanic basin at water depths ranging from 2300 to 4200 m. A series of scarps and immature canyons have developed with escarpments showing pronounced relief at the landslide heads. The triggering mechanisms of platform margin collapses and slope landslides are attributed to sediment aggradation, slope oversteepening, gravity flows, relative sea-level changes, surface monsoon currents, and deep cyclonic circulation. The canyon evolution is explained through four stages: Inception stage, sediment instability on platform margin and slope-toe; Expansion stage, the presence of platform margin collapses and slope landslides; Development stage, the initiation of submarine canyons eroded by gravity flows with downslope and retrogressive erosion; Present stage, the upper slope canyon incised into the landslide area and ultimately integrated with the lower slope canyon, creating an elongated modern canyon. This work contributes to enhance our understanding of the detailed morphology, transport processes, and triggering mechanisms of submarine canyons in the pure carbonate systems.
A non-enhanced CT-based deep learning diagnostic system for COVID-19 infection at high risk among lung cancer patients
Authors: Du Tianming , Sun Yihao , Wang Xinghao , Jiang Tao , Xu Ning , Boukhers Zeyd , Grzegorzek Marcin , Sun Hongzan , Li Chen
Published: August 2024

Background

Pneumonia and lung cancer have a mutually reinforcing relationship. Lung cancer patients are prone to contracting COVID-19, with poorer prognoses. Additionally, COVID-19 infection can impact anticancer treatments for lung cancer patients. Developing an early diagnostic system for COVID-19 pneumonia can help improve the prognosis of lung cancer patients with COVID-19 infection.

Method

This study proposes a neural network for COVID-19 diagnosis based on non-enhanced CT scans, consisting of two 3D convolutional neural networks (CNN) connected in series to form two diagnostic modules. The first diagnostic module classifies COVID-19 pneumonia patients from other pneumonia patients, while the second diagnostic module distinguishes severe COVID-19 patients from ordinary COVID-19 patients. We also analyzed the correlation between the deep learning features of the two diagnostic modules and various laboratory parameters, including KL-6.

Result

The first diagnostic module achieved an accuracy of 0.9669 on the training set and 0.8884 on the test set, while the second diagnostic module achieved an accuracy of 0.9722 on the training set and 0.9184 on the test set. Strong correlation was observed between the deep learning parameters of the second diagnostic module and KL-6.

Conclusion

Our neural network can differentiate between COVID-19 pneumonia and other pneumonias on CT images, while also distinguishing between ordinary COVID-19 patients and those with white lung. Patients with white lung in COVID-19 have greater alveolar damage compared to ordinary COVID-19 patients, and our deep learning features can serve as an imaging biomarker.
Mutations in the WG and GW motifs of the three RNA silencing suppressors of grapevine fanleaf virus alter their systemic suppression ability and affect virus infectivity
Authors: Choi Jiyeong , Browning Scottie , Schmitt-Keichinger Corinne , Fuchs Marc
Published: August 2024

Viral suppressors of RNA silencing (VSRs) encoded by grapevine fanleaf virus (GFLV), one of the most economically consequential viruses of grapevine (Vitis spp.), were recently identified. GFLV VSRs include the RNA1-encoded protein 1A and the putative helicase protein 1BHel, as well as their fused form (1ABHel). Key characteristics underlying the suppression function of the GFLV VSRs are unknown. In this study, we explored the role of the conserved tryptophan-glycine (WG) motif in protein 1A and glycine-tryptophan (GW) motif in protein 1BHel in their systemic RNA silencing suppression ability by co-infiltrating Nicotiana benthamiana 16c line plants with a GFP silencing construct and a wildtype or a mutant GFLV VSR. We analyzed and compared wildtype and mutant GFLV VSRs for their (i) efficiency at suppressing RNA silencing, (ii) ability to limit siRNA accumulation, (iii) modulation of the expression of six host genes involved in RNA silencing, (iv) impact on virus infectivity in planta, and (v) variations in predicted protein structures using molecular and biochemical assays, as well as bioinformatics tools such as AlphaFold2. Mutating W to alanine (A) in WG of proteins 1A and 1ABHel abolished their ability to induce systemic RNA silencing suppression, limit siRNA accumulation, and downregulate NbAGO2 expression by 1ABHel. This mutation in the GFLV genome resulted in a non-infectious virus. Mutating W to A in GW of proteins 1BHel and 1ABHel reduced their ability to suppress systemic RNA silencing and abolished the downregulation of NbDCL2, NbDCL4,, and NbRDR6 expression by 1BHel. This mutation in the GFLV genome delayed infection at the local level and inhibited systemic infection in planta. Double mutations of W to A in WG and GW of protein 1ABHel abolished its ability to induce RNA silencing suppression, limit siRNA accumulation, and downregulate NbDCL2 and NbRDR6 expression. Finally, in silico protein structure prediction indicated that a W to A substitution potentially modifies the structure and physicochemical properties of the three GFLV VSRs. Together, this study provided insights into the specific roles of WG/GW not only in GFLV VSR functions but also in GFLV biology.
Characterizing the clinical heterogeneity of early symptomatic Alzheimer’s disease: a data-driven machine learning approach
Authors: Wang Xiwu , Ye Teng , Jiang Deguo , Zhou Wenjun , Zhang Jie ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2024

Introduction

Alzheimer’s disease (AD) is highly heterogeneous, with substantial individual variabilities in clinical progression and neurobiology. Amyloid deposition has been thought to drive cognitive decline and thus a major contributor to the variations in cognitive deterioration in AD. However, the clinical heterogeneity of patients with early symptomatic AD (mild cognitive impairment or mild dementia due to AD) already with evidence of amyloid abnormality in the brain is still unknown.

Methods

Participants with a baseline diagnosis of mild cognitive impairment or mild dementia, a positive amyloid-PET scan, and more than one follow-up Alzheimer’s Disease Assessment Scale-Cognitive Subscale-13 (ADAS-Cog-13) administration within a period of 5-year follow-up were selected from the Alzheimer’s Disease Neuroimaging Initiative database (n = 421; age = 73±7; years of education = 16 ± 3; percentage of female gender = 43%; distribution of APOE4 carriers = 68%). A non-parametric k-means longitudinal clustering analysis in the context of the ADAS-Cog-13 data was performed to identify cognitive subtypes.

Results

We found a highly variable profile of cognitive decline among patients with early AD and identified 4 clusters characterized by distinct rates of cognitive progression. Among the groups there were significant differences in the magnitude of rates of changes in other cognitive and functional outcomes, clinical progression from mild cognitive impairment to dementia, and changes in markers presumed to reflect neurodegeneration and neuronal injury. A nomogram based on a simplified logistic regression model predicted steep cognitive trajectory with an AUC of 0.912 (95% CI: 0.88 – 0.94). Simulation of clinical trials suggested that the incorporation of the nomogram into enrichment strategies would reduce the required sample sizes from 926.8 (95% CI: 822.6 – 1057.5) to 400.9 (95% CI: 306.9 – 516.8).

Discussion

Our findings show usefulness in the stratification of patients in early AD and may thus increase the chances of finding a treatment for future AD clinical trials.
Cognitive mechanisms of learning in sequential decision-making under uncertainty: an experimental and theoretical approach
Authors: Cecchini Gloria , DePass Michael , Baspinar Emre , Andujar Marta , Ramawat Surabhi , Pani Pierpaolo , Ferraina Stefano , Destexhe Alain , Moreno-Bote Rubén , Cos Ignasi
Published: August 2024

Learning to make adaptive decisions involves making choices, assessing their consequence, and leveraging this assessment to attain higher rewarding states. Despite vast literature on value-based decision-making, relatively little is known about the cognitive processes underlying decisions in highly uncertain contexts. Real world decisions are rarely accompanied by immediate feedback, explicit rewards, or complete knowledge of the environment. Being able to make informed decisions in such contexts requires significant knowledge about the environment, which can only be gained via exploration. Here we aim at understanding and formalizing the brain mechanisms underlying these processes. To this end, we first designed and performed an experimental task. Human participants had to learn to maximize reward while making sequences of decisions with only basic knowledge of the environment, and in the absence of explicit performance cues. Participants had to rely on their own internal assessment of performance to reveal a covert relationship between their choices and their subsequent consequences to find a strategy leading to the highest cumulative reward. Our results show that the participants’ reaction times were longer whenever the decision involved a future consequence, suggesting greater introspection whenever a delayed value had to be considered. The learning time varied significantly across participants. Second, we formalized the neurocognitive processes underlying decision-making within this task, combining mean-field representations of competing neural populations with a reinforcement learning mechanism. This model provided a plausible characterization of the brain dynamics underlying these processes, and reproduced each aspect of the participants’ behavior, from their reaction times and choices to their learning rates. In summary, both the experimental results and the model provide a principled explanation to how delayed value may be computed and incorporated into the neural dynamics of decision-making, and to how learning occurs in these uncertain scenarios.
Association of hemoglobin-to-red cell distribution width ratio with the three-month outcomes in patients with acute ischemic stroke
Authors: Xie Xiaorui , He Keli , Zhang Yao , Wu Jianhua
Published: August 2024

Aim

To explore the association of Hemoglobin-to-Red Cell Distribution Width Ratio (HRR) with the risk of three-month unfavorable outcomes in acute ischemic stroke (AIS).

Methods

A secondary analysis was conducted based on a prospective cohort study. A total of 1,889 patients with AIS treated in South Korea from January 2010 to December 2016 were enrolled. Multivariable logistic regression was conducted to investigated the independent relationship between HRR and risk of three-month unfavorable outcomes in AIS. Fitted smoothing curves were used to determine non-linear correlations. The recursive method was employed to explore the turning point and build a two-piece linear regression model. In addition, a set of subgroup analyses were carried out to evaluate the relationship between HRR and risk of three-month unfavorable outcomes.

Results

Multivariate analysis in which potential confounders were adjusted for indicated that the risk of unfavorable outcomes was reduced by 10% for each unit increased of HRR [OR = 0.90, 95% CI: 0.84–0.96, p = 0.0024]. In addition, a non-linear relationship was observed between HRR and risk of three-month unfavorable outcomes, which had an inflection point of HRR was 10.57. The effect sizes and the confidence intervals on the left side of the inflection point were 0.83 (0.75, 0.91), p = 0.0001. On the right side of the inflection point, no association was found between HRR and the risk of three-month unfavorable outcomes.

Conclusion

This study demonstrates a negative association between HRR and risk of three-month unfavorable outcomes. The relationship between HRR and risk of three-month unfavorable outcomes is non-linear. The correlation is negative for HRR values less than 10.57. For, HRR higher than 10.57, HRR is not associated with the risk of three-month unfavorable outcomes.
Resting-state EEG features modulated by depressive state in healthy individuals: insights from theta PSD, theta-beta ratio, frontal-parietal PLV, and sLORETA
Authors: Li Pengcheng , Yokoyama Mio , Okamoto Daiki , Nakatani Hironori , Yagi Tohru
Published: August 2024

Depressive states in both healthy individuals and those with major depressive disorder exhibit differences primarily in symptom severity rather than symptom type, suggesting that there is a spectrum of depressive symptoms. The increasing prevalence of mild depression carries lifelong implications, emphasizing its clinical and social significance, which parallels that of moderate depression. Early intervention and psychotherapy have shown effective outcomes in subthreshold depression. Electroencephalography serves as a non-invasive, powerful tool in depression research, with many studies employing it to discover biomarkers and explore underlying mechanisms for the identification and diagnosis of depression. However, the efficacy of these biomarkers in distinguishing various depressive states in healthy individuals and in understanding the associated mechanisms remains uncertain. In our study, we examined the power spectrum density and the region-based phase-locking value in healthy individuals with various depressive states during their resting state. We found significant differences in neural activity, even among healthy individuals. Participants were categorized into high, middle, and low depressive state groups based on their response to a questionnaire, and eyes-open resting-state electroencephalography was conducted. We observed significant differences among the different depressive state groups in theta- and beta-band power, as well as correlations in the theta–beta ratio in the frontal lobe and phase-locking connections in the frontal, parietal, and temporal lobes. Standardized low-resolution electromagnetic tomography analysis for source localization comparing the differences in resting-state networks among the three depressive state groups showed significant differences in the frontal and temporal lobes. We anticipate that our study will contribute to the development of effective biomarkers for the early detection and prevention of depression.
Case report: A large gastric calcifying fibrous tumor treated with endoscopic submucosal excavation
Authors: Zhong Ziyou , Li Zhenguo , Xing Yufeng , Guo Shaoju
Published: August 2024

Gastric calcifying fibrous tumor (CFT) is a rare benign mesenchymal tumor. Several previous studies have reported surgical resection for gastric CFT larger than 20mm for the difficulty in preoperative diagnosis. Here, we report a rare case of large gastric CFT treated with endoscopic submucosal excavation (ESE). A 70-year-old woman presented with recurrent epigastric pain and underwent endoscopy, which revealed a 35mm-sized submucosal tumor in the gastric body. ESE was performed after imaging examination and endoscopic ultrasonography. En bloc resection was achieved, but due to the specimen’s substantial size and difficulty in mincing, it posed challenges for removal through the mouth. Finally, the specimen was temporarily placed in the stomach and was completely removed two days later. The diagnosis was confirmed based on pathological and immunohistochemical findings. There was no recurrence during the patient’s 11-month follow-up. We provided a case report related to the diagnosis and endoscopic treatment for large gastric CFT. In addition, our experience of temporarily leaving a large postoperative specimen, considered a benign lesion, in the stomach for later removal was successful but requires appropriate timing to avoid blockage of the gastrointestinal tract.