bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGARUH PEMBERIAN PUPUK ORGANIK CAIR DAN PUPUK NPK TERHADAP PERTUMBUHAN DAN PRODUKSI TANAMAN JAGUNG MANIS (Zea mays L. Saccaharata Sturt)
Authors: Mustadir Mustadir , Subaedah St. , Ibrahim Bakhtiar
Published: June 2024

This study aims to determine the effect of providing Mitra Flora liquid organic fertilizer and NPK fertilizer on sweet corn plant production growth. This research was conducted in Tampinna Village, Angkona District, East Luwu Regency, from August to November 2019. The first factor was a liquid organic waste with 4 levels, namely no liquid organic waste with a concentration of 1, 2, and cc/liter of water. The second factor is the dose of NPK fertilizer with 3 levels, namely 100, 200, and 300 kg/ha. From the two factors, 12 treatment combinations were obtained, and each treatment combination was repeated three times so that there were 36 experimental units. The results showed that the application of liquid organic fertilizer for the flora partners with a dose of 2 to 3 cc/liter of water obtained more leaves. Likewise, applying NPK fertilizer of as much as 300 kg/ha resulted in better growth and production of sweet corn. The interaction between the application of Mitra Flora liquid organic fertilizer 3 cc/liter of water and the application of Among Tani 300 kg/ha NPK fertilizer gave the best results on the parameters of plant height, number of leaves, length of the ear, and weight of the ear
Azacitidine as epigenetic priming for chemotherapy is safe and well-tolerated in infants with newly diagnosed KMT2A-rearranged acute lymphoblastic leukemia: Children’s Oncology Group trial AALL15P1
Authors: Guest Erin M. , Kairalla John A. , Devidas Meenakshi , Hibbitts Emily , Carroll Andrew J. , Heerema Nyla A. , Kubaney Holly R. , August Margaret A. , Ramesh Sidharth , Yoo Byunggil , Farooqi Midhat S. , Pauly Melinda G. , Wechsler Daniel S. , Miles Rodney R. , Reid Joel M. , Kihei Cynthia D. , Gore Lia , Raetz Elizabeth A. , Hunger Stephen P. , Loh Mignon L. , Brown Patrick A.
Published: June 2024

Infants less than 1 year old diagnosed with KMT2A-rearranged (KMT2A-r) acute lymphoblastic leukemia (ALL) are at high risk of remission failure, relapse, and death due to leukemia, despite intensive therapies. Infant KMT2A-r ALL blasts are characterized by DNA hypermethylation. Epigenetic priming with DNA methyltransferase inhibitors increases the cytotoxicity of chemotherapy in preclinical studies. The Children’s Oncology Group trial AALL15P1 tested the safety and tolerability of five days of azacitidine immediately prior to the start of chemotherapy on day six, in four post-induction chemotherapy courses for infants with newly diagnosed KMT2A-r ALL. The treatment was welltolerated, with only two of 31 evaluable patients (6.5%) experiencing dose-limiting toxicity. Whole genome bisulfite sequencing of peripheral blood mononuclear cells (PBMCs) demonstrated decreased DNA methylation in 87% of samples tested following five days of azacitidine. Event-free survival was similar to prior studies of newly diagnosed infant ALL. Azacitidine is safe and results in decreased DNA methylation of PBMCs in infants with KMT2A-r ALL, but the incorporation of azacitidine to enhance cytotoxicity did not impact survival. Clinicaltrials.gov identifier: NCT02828358.
KORELASI KETERAMPILAN METAKOGNITIF DENGAN HASIL BELAJAR SISWA PADA MATERI HIDROKARBON
Authors: Indah Permata Sari  , Febrian Solikhin  , Rina Elvia
Published: June 2024

Penelitian ini merupakan penelitian deskriptif dengan pendekatan kuantitatif bertujuan untuk mendeskripsikan profil keterampilan metakognitif, hasil belajar siswa, dan korelasi keterampilan metakognitif terhadap hasil belajar siswa pada materi hidrokarbon. Penelitian ini dilakukan di SMAN 5 Kota Bengkulu. Subjek penelitian ini adalah kelas XI MIPA 3, XI MIPA 4 dan XI MIPA 5 yang berjumlah 105 siswa yang dipilih berdasarkan teknik purposive sampling dari populasi sebanyak 7 kelas. Pengumpulan data dilakukan dengan cara tes menggunakan instrumen tes tertulis dan non tes menggunakan kuesioner. Analisis data untuk uji korelasi menggunakan aplikasi SPPS 23. Hasil penelitian pada kuesioner keterampilan metakognitif diperoleh sebesar 85,2% yang menunjukkan bahwa keterampilan metakognitif siswa berada pada kategori sangat baik. Aspek keterampilan metakognitif terendah pada bagian keterampilan evaluasi (evaluating skills) diperoleh sebesar 82,8%  yang menunjukkan bahwa sebagian siswa belum dapat merangkum apa yang dibuat, belum memahami dalam menjawab persoalan dan kurang teliti dalam memeriksa jawaban yang telah dibaut pada materi hidrokarbon. Hasil penelitian terhadap hasil belajar siswa pada materi hidrokarbon diperoleh bahwa sebanyak 61,90% siswa pada kategori sangat baik, dan 38,10% pada kategori siswa baik. Hasil uji korelasi menunjukkan adanya hubungan yang positif dan signifikan antara keterampilan metakognitif dengan hasil belajarnya yang terlihat dari nilai koefisien korelasi sebesar 0,919 serta nilai sig. (2-tailed) sebesar 0,003. Hal tersebut menunjukkan bahwa korelasi keterampilan metakognitif dengan hasil belajar siswa pada materi hidrokarbon berada pada kategori sangat kuat yang menunjukkan bahwa siswa mampu menuliskan, menyusun serta membedakan berbagai struktur senyawa.
PENGEMBANGAN BAHAN AJAR SISTEM KOLOID BERBASIS WEB BERBANTUAN APLIKASI EXE LEARNING
Authors: Wahyu Ningsih Elen , Handayani Dewi , Nurhamidah
Published: June 2024

Penelitian ini bertujuan untuk mengembangkan bahan ajar sistem koloid berbasis web berbantuan aplikasi exe-learning. Model pengembangan yang digunakan yaitu model 4-D (Four-D) yang terdiri dari tahap define, design, develop dan disseminate. Penelitian dilakukan di SMA Negeri 2 Bengkulu Utara dengan subjek penelitian yaitu 12 siswa  kelas XI MIPA  2 untuk uji coba skala kecil, dan 34 siswa kelas XI MIPA 3 untuk uji coba skala besar. Instrumen yang digunakan yaitu lembar wawancara, angket kebutuhan siswa, lembar validasi materi dan media, angket respon siswa dan guru, serta lembar pretest dan posttest. Hasil penelitian ini menunjukan bahwa bahan ajar sistem koloid berbasis web dinyatakan sangat layak oleh ahli media dan ahli materi dengan persentase dari aspek media 93,13% dan aspek materi sebesar 86,42%, respon siswa terhadap bahan ajar sistem koloid berbasis web berada pada kategori sangat baik dengan persentase rata-rata sebesar 89,56%. Hasil belajar setelah menggunakan bahan ajar sistem koloid berbasis web yang dikembangkan dengan aplikasi exe-learning terjadi peningkatan dengan rata-rata skor N-gain 0,67 pada kriteria sedang dan respon guru terhadap bahan ajar sistem koloid berbasis web berada pada kategori sangat baik dengan persentase rata-rata sebesar 93,23%.
TRADITIONAL GAME BOYBOYAN: ANAYLISIS OF CHARACTER VALUES AND THE PROCESS OF CHARACTER BUILDING FOR EARLY CHILDHOOD
Authors: Putra Ari , Stiadi Elwan , Ismawati Dwi , Hidayat Dayat
Published: June 2024

Penelitian ini bertujuan untuk mendeskripsikan proses pembentukan nilai dan karakter anak usia dini melalui permainan tradisional boyboyan yang diadakan di lembaga pendidikan nonformal ECO Bambu Cipaku Bandung. Penelitian ini menggunakan metode kualitatif dengan pendekatan studi kasus. Subyek penelitian ini adalah peserta kegiatan literasi budaya yang melakukan kunjungan belajar melalui kegiatan rekreasi edukatif. Teknik pengumpulan data menggunakan wawancara, observasi, dan dokumentasi. Hasil penelitian menunjukkan bahwa terdapat nilai karakter dalam permainan tradisional boyboyan. Berdasarkan temuan, nilai karakter dapat dilihat dari kegiatan bermain yang dilakukan secara spontan dan berulang-ulang oleh para peserta sehingga terjadi pembentukan nilai dari sikap dan tindakan para peserta. Nilai-nilai karakter yang terkandung dalam permainan ini adalah nilai-nilai disiplin, kerja keras, kreatif, kebangsaan, rasa ingin tahu, kejujuran, tanggung jawab, menghargai prestasi, religius, toleransi, kemandirian, demokrasi, bersahabat/komunikatif, dan peduli sosial. Permainan tradisional bukan hanya permainan sederhana yang dapat memberikan kesenangan bagi pemainnya tetapi tanpa disadari bahwa kegiatan permainan tradisional memiliki banyak nilai karakter dan memiliki filosofi yang kuat bagi pembentukan jati diri peserta permainan. Penemuan nilai-nilai karakter dalam permainan tradisional boyboyan dapat dijadikan sebagai media dalam pembentukan karakter khususnya untuk kegiatan pembelajaran baik secara formal maupun informal. Keberlanjutan dalam inventarisasi nilai-nilai karakter dalam permainan tradisional harus terus digali sehingga dapat menjadi inovasi dalam pembelajaran dan upaya pelestarian budaya lokal.
Pola Belajar Anak Penyandang Low Vision Pada Anak Usia Dini
Authors: Handayani Oktarina Dwi , Rizkya Riedha Silla
Published: June 2024

Dalam pendidikan formal tidak menutup kemungkinan terdapat anak yang memiliki keterbatasan, contohnya seperti anak penyandang low vision. Maka, sebagian pendidik harus berusaha agar anak dapat memahami materi yang telah disampaikan. Tujuan dari penelitian ini untuk mengetahui pola belajar bagi anak low vision usia 5-6 tahun. Penelitian ini dilakukan dengan pendekatan kualitatif studi kasus dengan subjek anak penyandang low vision usia 5-6 tahun. Data yang dikumpulkan melalui observasi, wawancara, dan dokumentasi pada aktivitas pembelajaran anak di lingkungan sekolah. Data dianalisis dengan menggunakan triangulasi sumber data. Statement dari guru dicocokkan dengan observasi pada anak selama pembelajarn. Hasil penelitian menunjukkan bahwa pola belajar anak low vision dilakukan melalui terbimbing oleh pendidik. Pendidik memberikan pendampingan secara intensif terhadap anak low vision dibantu dengan penggunaan media audio-visual. Pada pola belajar mandiri, kelompok dan tutor sebaya tidak efektif digunakan dalam pembelajaran sehingga level tutor perlu lebih tinggi yaitu membutuhkan pendidik.
Analysis of Students' Design Thinking in Information Technology Innovation
Authors: Indriaturrahmi Indriaturrahmi , Prayogi Saiful , Asy'ari Muhammad , Samsuri Taufik
Published: June 2024

This study delves into the design thinking characteristics among students in the field of information technology innovation, examining their competencies within the context of the Information Technology Education program at Mandalika University of Education - Indonesia. Employing an exploratory descriptive research design, the research focuses on 30 students, utilizing the Design Thinking Scale to assess six crucial dimensions: comfort with uncertainty and risks, human-centeredness, mindfulness of the process and impacts on others, collaborative work with diversity, orientation to learning by making and testing, and confidence and optimism to use creativity. The findings reveal a comprehensive understanding of the nuanced aspects of students' design thinking capabilities, indicating areas for improvement. Notably, students exhibit discomfort with uncertainty and risks, signaling a need for interventions to enhance resilience and adaptability. Human-centeredness, collaborative work with diversity, and mindfulness to the process receive "Poor" and "Fair" ratings, emphasizing the importance of fostering user-centric approaches and enhancing collaborative competencies. While students demonstrate a moderate level of competency in practical learning and creative application, there is room for improvement in orientation to learning by making and testing and confidence and optimism to use creativity. The overall "Poor" rating for the average design thinking score suggests a collective need for targeted interventions and educational strategies. This study contributes to the ongoing discourse on design thinking in IT education. It offers insights that can inform tailored pedagogical approaches and interventions to enhance students' design thinking capabilities in preparation for the dynamic challenges of the evolving information technology landscape.
Examining the Methodological Anatomies of Studies on Teaching English as a Foreign Language from a Techno Pedagogical Perspective
Authors: Karslı Veysel , Çilligöl Karabey Sinem , Bayrak Meva , Karaman Selçuk
Published: June 2024

Changes in technology and the increase in its potential for language teaching have made it possible to restructure Teaching English as a Foreign Language (TEFL) models today. In this context, the aim of this study is to examine the methodological anatomy of theses on technology integration in TEFL from a techno-pedagogical perspective. In this direction, the descriptive features, methodological features, examined variables, used technological environments/tools/materials and the roles of instructors and students were examined. Within the scope of this study, content analysis was used for 110 graduate theses conducted in Turkey on technology integration in TEFL. According to the results of the study, it has been determined that the effects of different technologies on various skills have been examined with different research methods from past to present in the TEFL processes, and again in this process, studies tried to focus on skills that are almost directly related to the potential of each technology. However, in most of these research processes, it was observed that the potential offered by the relevant technology was utilized at a very basic level and in relation to this, especially students were given passive roles. As a result of the study, research and application suggestions were made that can better reveal the real potentials of related technologies in technology-assisted TEFL processes.
SINIF ÖĞRETMENLERİNİN GÖRÜŞLERİNE GÖRE BİRİNCİ SINIF ÖĞRENCİLERİNİN İLKOKULA HAZIRBULUNUŞLUK DÜZEYLERİ
Authors: Bayramoğlu Özge Yıldız , Çevik Kansu Ceren
Published: June 2024

Çocuğun okul ortamına fiziksel, duygusal, psikolojik olarak uyum sağlayabilmesi ve kendini iyi hissedebilmesi için bir olgunluğa ulaşmış olabilmesi gerekmektedir. Bu araştırmada ilkokul 1. sınıf düzeyindeki öğrencilerin hazırbulunuşluklarının birçok değişken açısından incelenmesi hedeflenmiştir. Araştırmanın yürütülmesinde tarama modelinden yararlanılmıştır. Araştırma evreni 2020-2021 öğretim yılında Samsun ilindeki ilkokul 1. sınıfları okutan sınıf öğretmenlerinden meydana gelmektedir. Araştırmada veri toplama araçları olarak İlkokula Hazırbulunuşluk Ölçeği ve araştırmacılar tarafından geliştirilen Kişisel Bilgi Formu kullanılmıştır. Verilerin analizinde kullanılan testler; parametrik olarak bağımsız gruplar için t testi, nonparametrik olarak Kruskal Wallis H testi ile Mann Whitney U testidir. Araştırmada, ilkokul 1. sınıf öğrencilerinin ilkokula hazırbulunuşluk düzeylerinin okula başlamadan önce sanatsal, sportif faaliyetlere katılma durumları, okula başlama ayları, anne ile babanın eğitim durumları, ailenin kaçıncı çocuğu oldukları, annenin çalışma durumu, veli ile evde etkinlik yapma durumu ve ailenin teknolojiyi kullanma sürelerine göre anlamlı farklılıklar tespit edilmiştir. Ancak öğrencilerin cinsiyetlerine göre ilkokula hazırbulnuşlukları arasında anlamlı bir farklılık görülmemiştir. Elde edilen bulgulara göre ailenin ilk çocuğu olanların okula hazırbulunuşluk düzeyleri diğerlerinden daha yüksek bulunurken, bu değişkenin ilkokula hazırbulunuşluk düzeyini belirlemede anlamlı bir farklılık oluşturmadığı tespit edilmiştir. Okul öncesinde sanatsal, sportif kurslara katılan çocukların, katılmayanlara göre; velisi ile evde etkinlik yapan çocukların yapmayanlara göre daha iyi hazırbulunuşluğa sahip oldukları ve ailenin teknoloji kullanma süresinin azaldığı durumlarda çocuklarının ilkokula hazırbulunuşluklarının arttığı görülmüştür.
Blood vessels in a dish: the evolution, challenges, and potential of vascularized tissues and organoids
Authors: Nwokoye Peter N. , Abilez Oscar J.
Published: June 2024

Vascular pathologies are prevalent in a broad spectrum of diseases, necessitating a deeper understanding of vascular biology, particularly in overcoming the oxygen and nutrient diffusion limit in tissue constructs. The evolution of vascularized tissues signifies a convergence of multiple scientific disciplines, encompassing the differentiation of human pluripotent stem cells (hPSCs) into vascular cells, the development of advanced three-dimensional (3D) bioprinting techniques, and the refinement of bioinks. These technologies are instrumental in creating intricate vascular networks essential for tissue viability, especially in thick, complex constructs. This review provides broad perspectives on the past, current state, and advancements in key areas, including the differentiation of hPSCs into specific vascular lineages, the potential and challenges of 3D bioprinting methods, and the role of innovative bioinks mimicking the native extracellular matrix. We also explore the integration of biophysical cues in vascularized tissues in vitro, highlighting their importance in stimulating vessel maturation and functionality. In this review, we aim to synthesize these diverse yet interconnected domains, offering a broad, multidisciplinary perspective on tissue vascularization. Advancements in this field will help address the global organ shortage and transform patient care.
Predictors of cognitive change in cognitively healthy older women in Panama: the PARI-HD study
Authors: Oviedo Diana C. , Tratner Adam E. , Rodríguez-Araña Sofía , Villarreal Alcibiades E. , Rangel Giselle , Carreira María B. , Britton Gabrielle B.
Published: June 2024

Background

Evidence suggests that a combination of biological and social factors influence risk of dementia differently for women and men. In healthy older women, several factors may contribute to changes in cognition.

Objective

Describe the characteristics associated with variation in cognition in a sample of cognitively healthy older Panamanian women.

Methods

The study includes cross-sectional analyses of cognitive domains at baseline (n = 357) and 17-month (SD = 2.0) follow-up (n = 200) for women aged 60 years and older enrolled in the Panama Aging Research Initiative-Health Disparities (PARI-HD) study. Instruments included clinical questionnaires, physiological measures, and a neuropsychological test battery assessing global cognition and seven cognitive domains. Multiple regression analyses examined the associations between demographic and clinical characteristics and cognition at baseline. Repeated measures analyses were used to investigate changes in cognition from baseline to follow-up.

Results

On average, participants were 68.6 years of age (SD = 5.9) with 16.1 years of education (SD = 4.7). Age, income, and education showed robust associations with baseline cognition. Subjective cognitive impairment was associated with lower performance in global cognition, verbal learning, and memory domains. Only performance in the attention domain decreased at follow-up, and subjective health state and depressive symptoms significantly predicted the change in attention.

Discussion

Our study findings contribute to the investigation of cognitive health in older Hispanic women and to the understanding of sociodemographic and health-related factors associated with cognitive decline and the progression to cognitive impairment and dementia.
The global role of G6PD in infection and immunity
Authors: Shah Shivang S. , Stone Elizabeth F. , Francis Richard O. , Karafin Matthew S.
Published: June 2024

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in humans. G6PD is an essential enzyme in the pentose phosphate pathway (PPP), generating NADPH needed for cellular biosynthesis and reactive oxygen species (ROS) homeostasis, the latter especially key in red blood cells (RBCs). Beyond the RBC, there is emerging evidence that G6PD exerts an immunologic role by virtue of its functions in leukocyte oxidative metabolism and anabolic synthesis necessary for immune effector function. We review these here, and consider the global immunometabolic role of G6PD activity and G6PD deficiency in modulating inflammation and immunopathology.
Identification and characterization of new structural scaffolds modulating the activity of Mycobacterium tuberculosis dihydroneopterin aldolase (FolB) in vitro
Authors: Falcão Virginia Carla de Almeida , Czeczot Alexia de Matos , Alam Mohammad Maqusood , Park Kyu-Ho Paul , Heo Jinyeong , Woo Minjeong , Camini Ana Micaela , Timmers Luis Fernando Saraiva Macedo , Shum David , Perelló Marcia Alberton , Basso Luiz Augusto , Machado Pablo , Bizarro Cristiano Valim , Delorme Vincent
Published: June 2024

Introduction

Antifolates were among the first broad-spectrum compounds used as antimycobacterial agents and can still be of use when no other therapeutic options are available. The discovery of compounds targeting the essential folate synthesis pathway could lead to new therapeutic agents to treat tuberculosis (TB). In particular, the enzyme required for the conversion of 7,8-dihydroneopterin (DHNP) to 6-hydroxymethyl-7,8-dihydropterin (HP) and glycolaldehyde (GA) in the folate pathway (MtbFolB, a dihydroneopterin aldolase - DHNA, EC 4.1.2.25), has received little attention as a potential drug target so far, as it is acting upstream of the clinically validated targets dihydropteroate synthase (DHPS; EC 2.5.1.15) and dihydrofolate reductase (DHFR; EC 1.5.1.3).

Methods

We conducted a small-scale diversity screening to identify MtbFolB inhibitors using a microplate-based enzyme inhibition assay. A total of 6,074 compounds were assembled, tested and confirmed in dose-response studies. A preliminary structure activity analysis was performed for the validated hit compounds, along with kinetic inhibition, time-dependent inhibition, as well as docking studies.

Results

The screening resulted in the selection of 19 hits spanning 5 independent clusters. Dose-response studies of re-synthesized hits and newly synthesized derivatives displayed compounds with IC50 values ranging from 2.6 to 47 µM. The structure activity analysis revealed that bi-sulfonamide compounds could be explored for further optimizations. Docking studies highlighted two modes of binding for pyrazol-3-one compounds and, for the sulfonamide series, indicated several interactions with the catalytic Tyrosine-54 (Tyr54D) and Lysine-99 (Lys99A) residues of MtbFolB.

Discussion

Through this work, we established that the MtbFolB assay was able to select small molecules with inhibitory activities, opening prospects for larger scale screening. The sulfonamide compound 13 was also identified as the first compound directed against MtbFolB with an antimycobacterial activity.
KEAP1 overexpression is correlated with poor prognosis and immune infiltration in liver hepatocellular carcinoma
Authors: Wei Xin , Tang Yigui , Zheng Meijuan , Xu Yuanhong , Wang Zhongxin
Published: June 2024

Purpose

Liver hepatocellular carcinoma (LIHC) is the most common type of liver cancer, but there is a lack of effective indicators for its early diagnosis and prognosis, so we explored the role of KEAP1 in LIHC patients in this study.

Methods

The Cancer Genome Atlas (TCGA) dataset was used to investigate the relationship between KEAP1 expression and clinicopathological features and prognosis of LIHC patients. KEAP1 expression related pathways were enriched by Gene Ontology (GO) and gene set enrichment analysis (GSEA). Besides, KEAP1 expression-related immune infiltration was performed by single-sample GSEA (ssGSEA), and function of immune cells was detected by flow cytometry.

Results

It was found that KEAP1 expression was significantly increased and correlated with overall survival of LIHC patients. A total of 231 differentially expressed genes (DEGs) between LIHC patients with high- and low-KEAP1 expression were found, which associated with various biological pathways. Besides, KEAP1 expression was positively correlated with the infiltration level of T helper cells and Th2 cells but negatively correlated with DCs and cytotoxic cells. Functional analysis revealed that the expression of IL 4 in Th2 cells and CD107a, GrA and GrB in cytotoxic cells was significantly greater in LIHC patients than in HCs. In addition, KEAP1 expression was closely correlated with liver function in LIHC patients.

Conclusion

Highly expressed KEAP1 was closely related to the diagnosis, prognosis, immune cell infiltration, and liver function of LIHC, which might promote the progression of LIHC through regulating cell development, signal transduction, and abnormal immune response. The current study partially revealed the role of KEAP1 in LIHC and provided a potential biomarker for the diagnosis, prognosis and treatment of LIHC.
Principle, application and challenges of development siRNA-based therapeutics against bacterial and viral infections: a comprehensive review
Authors: Motamedi Hamid , Ari Marzie Mahdizade , Alvandi Amirhoushang , Abiri Ramin
Published: June 2024

While significant progress has been made in understanding and applying gene silencing mechanisms and the treatment of human diseases, there have been still several obstacles in therapeutic use. For the first time, ONPATTRO, as the first small interfering RNA (siRNA) based drug was invented in 2018 for treatment of hTTR with polyneuropathy. Additionally, four other siRNA based drugs naming Givosiran, Inclisiran, Lumasiran, and Vutrisiran have been approved by the US Food and Drug Administration and the European Medicines Agency for clinical use by hitherto. In this review, we have discussed the key and promising advances in the development of siRNA-based drugs in preclinical and clinical stages, the impact of these molecules in bacterial and viral infection diseases, delivery system issues, the impact of administration methods, limitations of siRNA application and how to overcome them and a glimpse into future developments.
Exploring the diversity and potential functional characteristics of microbiota associated with different compartments of Schisandra chinensis
Authors: Hou Wenjuan , Xing Yanping , Xue Hefei , Huang Yanchang , Huang Yutong , Men Wenxiao , Yang Yanyun , Kang Tingguo , Dou Deqiang , Zheng Han , Xu Liang
Published: June 2024

Introduction

Symbiotic microbial have a significant impact on the growth and metabolism of medicinal plants. Schisandra chinensis is a very functionally rich medicinal herb; however, its microbial composition and diversity have been poorly studied.

Methods

In the present study, the core microbiomes associated with the rhizospheric soil, roots, stems, leaves, and fruits of S. chinensis from six geographic locations were analyzed by a macro-genomics approach.

Results

Alpha and beta diversity analyses showed that the diversity of microbial composition of S. chinensis fruits did not differ significantly among the geographic locations as compared to that in different plant compartments. Principal coordinate analysis showed that the microbial communities of S. chinensis fruits from the different ecological locations were both similar and independent. In all S. chinensis samples, Proteobacteria was the most dominant bacterial phylum, and Ascomycota and Basidiomycota were the most dominant fungal phyla. Nitrospira, Bradyrhizobium, Sphingomonas, and Pseudomonas were the marker bacterial populations in rhizospheric soils, roots, stems and leaves, and fruits, respectively, and Penicillium, Golubevia, and Cladosporium were the marker fungal populations in the rhizospheric soil and roots, stems and leaves, and fruits, respectively. Functional analyses showed a high abundance of the microbiota mainly in biosynthesis.

Discussion

The present study determined the fungal structure of the symbiotic microbiome of S. chinensis, which is crucial for improving the yield and quality of S. chinensis.
Areca palm velarivirus 1 infection caused disassembly of chloroplast and reduction of photosynthesis in areca palm
Authors: Cao Xianmei , Gao Baosen , Lu Jie , Wang Hongxing , Zhao Ruibai , Huang Xi
Published: June 2024

The expansion of betel palm cultivation is driven by rising demand for betel nut, yet this growth is accompanied by challenges such as decreased agricultural biodiversity and the spread of infectious pathogens. Among these, Yellow Leaf Disease (YLD) emerges as a prominent threat to betel palm plantation. Areca Palm Velarivirus 1 (APV1) has been identified as a primary causative agent of YLD, precipitating leaf yellowing, stunted growth, and diminished yield. However, the precise mechanisms underlying APV1-induced damage remain elusive. Our study elucidates that APV1 infiltrates chloroplasts, instigating severe damage and consequential reductions in chlorophyll a/b and carotene levels, alongside notable declines in photosynthetic efficiency. Moreover, APV1 infection exerts broad regulatory effects on gene expression, particularly suppressing key genes implicated in chloroplast function and photosynthesis. These disruptions correlate with growth retardation, yield diminishment, and compromised nut quality. Intriguingly, the paradoxical destruction of the host's photosynthetic machinery by APV1 prompts inquiry into its evolutionary rationale, given the virus's dependence on host resources for replication and proliferation. Our findings reveal that APV1-induced leaf yellowing acts as a beacon for transmission vectors, hinting at a nuanced “host-pathogen-vector co-evolutionary” dynamic.
Revolutionizing migraine management: advances and challenges in CGRP-targeted therapies and their clinical implications
Authors: Özge A. , Baykan B. , Bıçakçı Ş. , Ertaş M. , Atalar A. Ç. , Gümrü S. , Karlı N.
Published: June 2024

Migraine, a prevalent neurological disorder, affects approximately 14.1% of the global population and disproportionately impacts females. This debilitating condition significantly compromises quality of life, productivity, and incurs high healthcare costs, presenting a challenge not only to individuals but to societal structures as a whole. Despite advances in our understanding of migraine pathophysiology, treatment options remain limited, necessitating ongoing research into effective therapies. This review delves into the complexity of migraine management, examining the roles of genetic predisposition, environmental influences, personalized treatment approaches, comorbidities, efficacy and safety of existing acute and preventive treatments. It further explores the continuum between migraine and tension-type headaches and discusses the intricacies of treating various migraine subtypes, including those with and without aura. We emphasize the recent paradigm shift toward trigeminovascular activation and the release of vasoactive substances, such as calcitonin gene-related peptide (CGRP), which offer novel therapeutic targets. We assess groundbreaking clinical trials, pharmacokinetic and pharmacodynamic perspectives, safety, tolerability, and the real-world application of CGRP monoclonal antibodies and gepants. In the face of persisting treatment barriers such as misdiagnosis, medication overuse headaches, and limited access to specialist care, we discuss innovative CGRP-targeted strategies, the high cost and scarcity of long-term efficacy data, and suggest comprehensive solutions tailored to Turkiye and developing countries. The review offers strategic recommendations including the formulation of primary care guidelines, establishment of specialized outpatient clinics, updating physicians on novel treatments, enhancing global accessibility to advanced therapies, and fostering patient education. Emphasizing the importance of lifestyle modifications and holistic approaches, the review underscores the potential of mass media and patient groups in disseminating critical health information and shaping the future of migraine management.
Cathodal HD-tDCS above the left dorsolateral prefrontal cortex increases environmentally sustainable decision-making
Authors: Wyss Annika M. , Baumgartner Thomas , Guizar Rosales Emmanuel , Soutschek Alexander , Knoch Daria
Published: June 2024

Environmental sustainability is characterized by a conflict between short-term self-interest and longer-term collective interests. Self-control capacity has been proposed to be a crucial determinant of people’s ability to overcome this conflict. Yet, causal evidence is lacking, and previous research is dominated by the use of self-report measures. Here, we modulated self-control capacity by applying inhibitory high-definition transcranial current stimulation (HD-tDCS) above the left dorsolateral prefrontal cortex (dlPFC) while participants engaged in an environmentally consequential decision-making task. The task includes conflicting and low conflicting trade-offs between short-term personal interests and long-term environmental benefits. Contrary to our preregistered expectation, inhibitory HD-tDCS above the left dlPFC, presumably by reducing self-control capacity, led to more, and not less, pro-environmental behavior in conflicting decisions. We speculate that in our exceptionally environmentally friendly sample, deviating from an environmentally sustainable default required self-control capacity, and that inhibiting the left dlPFC might have reduced participants’ ability to do so.
Estimating carbon and water footprints associated with commercial milk formula production and use: development and implications of the Green Feeding Climate Action Tool
Authors: Smith Julie P. , Borg Bindi , Nguyen Tuan T. , Iellamo Alessandro , Pramono Andini , Mathisen Roger
Published: June 2024

Carbon offset frameworks like the UN Clean Development Mechanism (CDM) have largely overlooked interventions involving food, health, and care systems, including breastfeeding. The innovative Green Feeding Climate Action Tool (GFT) assesses the environmental impact of commercial milk formula (CMF) use, and advocates for breastfeeding support interventions as legitimate carbon offsets. This paper provides an overview of the GFT’s development, key features, and potential uses. The offline and online GFT were developed using the DMADV methodology (Define, Measure, Analyze, Design, Verify). The GFT reveals that the production and use of CMF by infants under 6 months results in annual global greenhouse gas (GHG) emissions of between 5.9 and 7.5 billion kg CO2 eq. and consumes 2,562.5 billion liters of water. As a national example, in India, one of the world’s most populous countries, CMF consumption requires 250.6 billion liters of water and results in GHG emissions ranging from 579 to 737 million kg CO2 eq. annually, despite the country’s high breastfeeding prevalence among infants under 6 months. The GFT mainly draws on data for low- and middle-income countries (LMICs), as many high-income countries (HICs) do not collect suitable data for such calculations. Despite poor official data on breastfeeding practices in HICs, GFT users can input their own data from smaller-scale surveys or their best estimates. The GFT also offers the capability to estimate and compare baseline with counterfactual scenarios, such as for interventions or policy changes that improve breastfeeding practices. In conclusion, the GFT is an important innovation to quantify CMF’s environmental impact and highlight the significance of breastfeeding for planetary as well as human health. Women’s contributions to environmental preservation through breastfeeding should be recognized, and breastfeeding interventions and policies should be funded as legitimate carbon offsets. The GFT quantifies CMF’s carbon and water footprints and facilitates financing breastfeeding support as a carbon offset initiative under CDM funding facilities.
Different MRI-based radiomics models for differentiating misdiagnosed or ambiguous pleomorphic adenoma and Warthin tumor of the parotid gland: a multicenter study
Authors: Yang Jing , Bi Qiu , Jin Yiren , Yang Yong , Du Ji , Zhang Hongjiang , Wu Kunhua
Published: June 2024

Purpose

To evaluate the effectiveness of MRI-based radiomics models in distinguishing between Warthin tumors (WT) and misdiagnosed or ambiguous pleomorphic adenoma (PA).

Methods

Data of patients with PA and WT from two centers were collected. MR images were used to extract radiomic features. The optimal radiomics model was found by running nine machine learning algorithms after feature reduction and selection. To create a clinical model, univariate logistic regression (LR) analysis and multivariate LR were used. The independent clinical predictors and radiomics were combined to create a nomogram. Two integrated models were constructed by the ensemble and stacking algorithms respectively based on the clinical model and the optimal radiomics model. The models’ performance was evaluated using the area under the curve (AUC).

Results

There were 149 patients included in all. Gender, age, and smoking of patients were independent clinical predictors. With the greatest average AUC (0.896) and accuracy (0.839) in validation groups, the LR model was the optimal radiomics model. In the average validation group, the radiomics model based on LR did not have a higher AUC (0.795) than the clinical model (AUC = 0.909). The nomogram (AUC = 0.953) outperformed the radiomics model in terms of discrimination performance. The nomogram in the average validation group had a highest AUC than the stacking model (0.914) or ensemble model (0.798).

Conclusion

Misdiagnosed or ambiguous PA and WT can be non-invasively distinguished using MRI-based radiomics models. The nomogram exhibited excellent and stable diagnostic performance. In daily work, it is necessary to combine with clinical parameters for distinguishing between PA and WT.
Addition of eptifibatide and manual thrombus aspiration to ticagrelor does not improve long-term survival after STEMI treated with primary PCI
Authors: Călburean Paul-Adrian , Grebenișan Paul , Nistor Ioana-Andreea , Pal Krisztina , Vacariu Victor , Drincal Reka-Katalin , Ion Alissa Anamaria , Adorján István , Oltean Tiberiu , Hadadi László
Published: June 2024

Background: Current guidelines recommend that glycoprotein IIb/IIIa inhibitor (GPI) and manual aspiration thrombectomy should not be routinely used in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI), although there is a lack of dedicated studies. The aim of this study was to examine the impact of combined usage of a potent P2Y12 inhibitor, GPI, and manual aspiration thrombectomy on long-term survival after STEMI.

Methods: All STEMI patients treated by pPCI in a tertiary center who have been included prospectively in the local PCI registry between January 2016 and December 2022 were analyzed in this study. Patients were excluded if they required oral anticoagulation or bridging between clopidogrel or ticagrelor during hospitalization.

Results: A total of 1,210 patients were included in the present study, with a median follow-up of 2.78 (1.00–4.88) years. Ticagrelor significantly reduced all-cause and cardiovascular-cause mortality [HR = 0.27 (0.21–0.34), p < 0.0001 and HR = 0.23 (0.17–0.30), p < 0.0001, respectively]. Eptifibatide significantly reduced all-cause and cardiovascular-cause mortality [HR = 0.72 (0.57–0.92), p = 0.002, and HR = 0.68 (0.52–0.89), p = 0.001, respectively]. Manual thrombus aspiration had no significant effect on both all-cause and cardiovascular-cause mortality. In multivariate Cox regression, all-cause mortality was reduced by ticagrelor, while eptifibatide or manual thrombus aspiration had no significant effect. However, cardiovascular-cause mortality was reduced by both ticagrelor and eptifibatide, while manual thrombus aspiration had no significant effect.

Conclusion: Ticagrelor consistently reduced cardiovascular and all-cause mortality, while eptifibatide reduced only cardiovascular mortality. Manual thrombus aspiration provided no long-term benefit. Our findings support the current guideline recommendation that GPI and manual aspiration thrombectomy should not be routinely used in treatment of STEMI with pPCI.
Screening rate constants in the simulation of rapid kinetics of chlorophyll a fluorescence using the Morris method
Authors: Lyu Hui , Lin Ying-Chao , Liakopoulos Georgios
Published: June 2024

Chlorophyllafluorescence, a sensitive and cost-effective probe, is widely used in photosynthetic research. Its rapid phase, occurring within 1 second under intense illumination, displays complex O-J-I-P transients, providing valuable insights into various aspects of photosynthesis. In addition to employing experimental approaches to measure the rapid Fluorescence Induction (FI) kinetics, mathematical modeling serves as a crucial tool for understanding the underlying mechanisms that drive FI dynamics. However, the significant uncertainty and arbitrary nature of selecting model parameters amplify concerns about the effectiveness of modeling tools in aiding photosynthesis research. Therefore, there is a need to gain a deeper understanding of how these models operate and how arbitrary parameter choices may influence their outcomes. In this study, we employed the Morris method, a global Sensitivity Analysis (SA) tool, to assess the significance of rate constants employed in an existing fluorescence model, particularly those linked to the entire electron transport chain, in shaping the rapid FI dynamics. In summary, utilizing the insights gained from the Morris SA allows for targeted refinement of the photosynthesis model, thereby improving our understanding of the complex processes inherent in photosynthetic systems.
Harnessing plant growth-promoting rhizobacteria, Bacillus subtilis and B. aryabhattai to combat salt stress in rice: a study on the regulation of antioxidant defense, ion homeostasis, and photosynthetic parameters
Authors: Siddika Ayesha , Rashid Alfi Anjum , Khan Shakila Nargis , Khatun Amena , Karim Muhammad Manjurul , Prasad P.V. Vara , Hasanuzzaman Mirza
Published: June 2024

Introduction

The ongoing global expansion of salt-affected land is a significant factor, limiting the growth and yield of crops, particularly rice (Oryza sativa L). This experiment explores the mitigation of salt-induced damage in rice (cv BRRI dhan100) following the application of plant growth-promoting rhizobacteria (PGPR).

Methods

Rice seedlings, at five- and six-weeks post-transplanting, were subjected to salt stress treatments using 50 and 100 mM NaCl at seven-day intervals. Bacterial cultures consisting of endophytic PGPR (Bacillus subtilis and B. aryabhattai) and an epiphytic PGPR (B. aryabhattai) were administered at three critical stages: transplantation of 42-day-old seedlings, vegetative stage at five weeks post-transplantation, and panicle initiation stage at seven weeks post-transplantation.

Results

Salt stress induced osmotic stress, ionic imbalances, and oxidative damage in rice plants, with consequent negative effects on growth, decrease in photosynthetic efficiency, and changes in hormonal regulation, along with increased methylglyoxal (MG) toxicity. PGPR treatment alleviated salinity effects by improving plant antioxidant defenses, restoring ionic equilibrium, enhancing water balance, increasing nutrient uptake, improving photosynthetic attributes, bolstering hormone synthesis, and enhancing MG detoxification.

Discussion

These findings highlight the potential of PGPR to bolster physiological and biochemical functionality in rice by serving as an effective buffer against salt stress–induced damage. B. subtilis showed the greatest benefits, while both the endophytic and epiphytic B. aryabhattai had commendable effects in mitigating salt stress–induced damage in rice plants.
The influence of observers on children’s conformity in moral judgment behavior
Authors: Lee Yoonha , Song Hyun-joo
Published: June 2024

Children autonomously make sound moral judgments based on internal criteria, but they tend to make erroneous judgments in the presence of social influences, and the reasons for these errors are not well understood. Thus, the current research investigated how the presence of observers who can see and listen to 3-year-old children’s judgments but who do not present their opinions influences children’s conformity in moral judgment behavior. In Experiment 1, the children (N = 30) were presented with pictures depicting prosocial behaviors and asked whether the behaviors were acceptable. The children’s tendency to change their answers after hearing the counterintuitive opinions of informants was then measured. The results showed that the children’s moral judgments were more likely to conform to that of the group in the presence of observers. Experiment 2 aimed to determine the reason children were more likely to conform to a group when being watched by observers in Experiment 1. Children (N = 30) were randomly assigned to two conditions with different observer conditions as follows. Observers were either wearing headsets, indicating that they could not hear the children’s responses, or had them hanging around their necks, indicating that they could. The results showed that children’s conformity behavior depended on whether observers could hear what they were saying. The current findings are expected to help elucidate not only social factors that affect children’s moral judgments but also the developmental mechanism of an observer effect.
The relationship between mental health literacy and professional psychological help-seeking behavior among Chinese college students: mediating roles of perceived social support and psychological help-seeking stigma
Authors: Yang Xiao , Hu Jun , Zhang Bingren , Ding Hua , Hu Danying , Li Hangdong
Published: June 2024

Introduction

Mental health literacy is viewed as a significant factor that may facilitate an individual’s pursuit of professional psychological assistance. However, it is important to explore further influencing factors that might underlie this association. This study, employing the framework of the Theory of Planned Behavior (TPB), aims to examine the relationship between mental health literacy and the behavior of seeking professional psychological help, with a focus on the potential mediating roles of perceived stigma and social support in this context.

Methods

We surveyed 911 college students in seven regions of China (406 males and 505 females, aged between 19 and 25 years old; Mage = 19.65, SD = 1.41) utilizing self-report measures, including the Mental Health Literacy Questionnaire, Professional Psychological Help-Seeking Behavior Scale, Professional Psychological Help-Seeking Stigma Scale, and Perceived Social Support Scale. A chain mediation model was developed to analyze the interconnections between mental health literacy, stigma related to seeking psychological help, perceived social support, and professional psychological help-seeking behaviors.

Results

The mediation effect analysis indicates that: (1) mental health literacy significantly positively correlates with professional psychological help-seeking behaviors; (2) both perceived social support and professional psychological help-seeking stigma significantly mediate the relationship between mental health literacy and professional psychological help-seeking behavior; (3) perceived social support and the stigma associated with seeking professional psychological help play a chained mediating effect between mental health literacy and the behavior of seeking professional psychological help.

Discussion

This study found that mental health literacy indirectly facilitates professional psychological help-seeking behaviors by enhancing the perception of social support and reducing the stigma associated with seeking such help. These findings help in understanding how improving mental health literacy and perceived social support while reducing stigma can increase the likelihood of individuals seeking professional psychological assistance. The results are significant for enhancing the utilization of mental health services and implementing mental health education programs in universities.