bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of the Flipped Learning Model on Creative Thinking Ability in the Revolution 4.0 era
Authors: Harso Aloisius , Amri Miftachul , Susiloningtyas Riyanti , Sanulita Henny , Widodo Hadi , Santosa Tomi Apra
Published: March 2024

Many applications of flipped learning have a huge impact on students' creative thinking ability in learning. However, no deep conclusions have been found and are still subjective.  This study aims to determine the influence of flipped learning to improve students' creative thinking skills in the era of the industrial revolution 4.0. This type of research is a meta-analysis.  The research data came from google scholar, Researchgaet, ScienceDirect and ERIC. The inclusion criteria in this study are research from SINTA and Scopus indexed journals; Research must be experimental or quasi-experimental; Research related to flipped learning models on students' creative thinking skills; Research published in 2020-2024; The study must have complete data to calculate the value of effect size; sample size (N) > 25 students. The results of the analysis of 15 journals concluded that there was a significant influence on students' creative thinking ability with a high mean effect size (ES = 1.12) criterion. These findings explain the application of flipped learning effectively helps teachers and students in improving creative thinking skills in the learning process.
Implementation of Classical Format Intelligent Character Education (PKC-KA) to Reduce Student Academic Procrastination
Authors: Asbi Asbi , Hasibuan M Fauzi , Sari Mawar
Published: March 2024

Prokrastinasi akademik merupakan salah satu permasalah yang sering terjadi, terutama dibidang akademik. Prokrastinasi akademik dapat didefinisikan sebagai kecenderungan seseorang dalam menunda kegiatan yang berkaitan dengan akademik. Salah satu penyebab terjadinya prokrastinasi  pada siswa yaitu rasa malas dan tidak memahami tugas yang diberikan oleh guru. Salah satu perilaku siswa yang mengarah  kepada prokrastinasi  akademik adalah tidak megumpulkan tugas sekolah sesuai waktu yang telah ditentukan sebelumnya. Sampel penelitian ini adalah siswa kelas X-IPS 1 dan X-IPS 2 MAN 1 Batubara  dengan  kelompok  eksperimen  sebanyak  32  orang siswa  dan kelompok kontrol sebanyak 32 orang siswa. Instrumen penelitian yang digunakan adalah model Skala Likert, selanjutnya akan dianalisis menggunakan uji Wilcoxon Signed Ranks Test dan uji Kolmogorov-Smirnov Two Independent Sampel dengan bantuan SPSS versi 26.00. Temuan  penelitian ini secara umum menunjukkan bahwa pendidikan karakter cerdas format klaskal (PKC-Ka) efektif untuk mengurangi prokrastinasi akademik pada siswa sehingga untuk selanjutnya dapat diberikan kepada siswa dalam upaya mengurangi prokrastinasi akademik siswa. Selanjutnya, temuan penelitian   secara   khusus   yaitu:   (1)  terdapat   perbedaan   yang   signifikan prokrastinasi akademik mahasiswa pada kelompok eksperimen sebelum   dan setelah diberikan   pendidikan karakter cerdas format klaskal (PKC-Ka), (2) terdapat perbedaan prokrastinasi akademik  mahasiswa pada kelompok kontrol sebelum dan setelah diberikan informasi konvensional dan (3) terdapat   perbedaan   prokrastinasi   akademik siswa   antara   kelompok eksperimen yang diberikan pendidikan karakter cerdas format klaskal (PKC-Ka)  dengan kelompok kontrol yang diberikan layanan informasi konvensional
Program Evaluation as a Foundation for Improving Program Quality in Educational Institutions
Authors: Partahian Partahian , Nisak Khoirun , Lubis Leli Hasanah , Tihawa Tihawa , Hutagalung Ruminda
Published: March 2024

Penelitian ini bertujuan untuk mengetahui konsep Evaluasi Program Sebagai Landasan Peningkatan Kualitas Program Dalam Lembaga Pendidikan. Metode penelitan ini adalah Library Research. Hasil penelitian ini yaitu Evaluasi program pendidikan memainkan peran yang sangat penting dalam meningkatkan kualitas program pendidikan. Konsep-konsep seperti menetapkan tujuan evaluasi yang jelas, menggunakan pendekatan sistematis, melibatkan stakeholder, memilih metode evaluasi yang tepat, dan menggunakan data yang berbasis bukti, adalah kunci dalam melakukan evaluasi yang efektif. Dengan menerapkan konsep-konsep ini dengan baik, lembaga pendidikan dapat memastikan bahwa program-program pendidikan yang mereka tawarkan selalu relevan, efektif, dan berdaya saing.
PELATIHAN CREATIVE INNOVATION START UP PROGRAM (CISUP) DI LITTLE SUN SCHOOL SURABAYA
Authors:   Widya Mandala Surabaya Catholic University, Sancoko Aldo Hardi , Tulipa Diyah ,   Widya Mandala Surabaya Catholic University, Lasmono Sandi Lenandi Soetrisno ,   Widya Mandala Surabaya Catholic University
Published: March 2024

Dorongan dari pemerintah untuk sekolah tingkat menengah yang dituntut untuk memiliki kompetensi berwirausaha mandiri sementara saat ini siswa di sekolah menengah masih minim kompetensi dan pengetahuan atau wawasan kewirausahaan menjadi peluang untuk mengembangkan dan memberikan insight bagi siswa tersebut. Pelaku abdimas memberikan solusi untuk mitra, siswa-siswa SMA Little Sun School Surabaya (baik kelas IPA maupun IPS) berupa pelatihan. Konsep pelatihan yang diberikan kepada mitra abdimas adalah cara berpikir kreatif dan inovatif, khususnya pada usaha mula-mula (startup). Program pelatihan ini diberi nama CISUP yang merupakan singkatan dari Creative Innovation Start Up Program. Program yang dimulai pada 18 Agustus 2021 sampai 10 November 2021 ini terbagi dari 12 kali pertemuan tiap minggunya, menghasilkan 3 konsep kreatif dan inovatif, yakni Bliss, Urgent!, Chance – Jihui(机会); difasilitasi oleh 4 dosen Fakultas Kewirausahaan: Andy Pratama Sulistyo, SM., MSM., Santho Vlennery Mettan, SM., MM., Dr. Diyah Tulipa, MM., Dr. Sandy Lenandi SL., MM., Aldo Hardi Sancoko, SE., MM; dan didampingi oleh 5 mahasiswa Fakultas Kewirausahaan. Tiga ide konsep kreatif inovatif yang merupakan tujuan dan target luaran tersebut tertuang dalam dokumen digital berbentuk website sederhana menggunakan WIX™, paparan presentasi, dan media pemasaran menggunakan IMOOJI™.
BAGAIMANA MENJADI UMKM YANG PRODUKTIF PADA WARGA UMKM RW 02 DAN RW 03 KELURAHAN MEDOKAN SEMAMPIR KECAMATAN SUKOLILO SURABAYA
Authors:   Universitas Katolik Widya Mandala Surabaya, Nagel P. Julius F. , Lindawati Tuty ,   Universitas Katolik Widya Mandala Surabaya, Muljani Ninuk ,   Universitas Katolik Widya Mandala Surabaya, Marsela Niken Dwi ,   Universitas Katolik Widya Mandala Surabaya, Monica Marshela Sheren ,   Universitas Katolik Widya Mandala Surabaya, Wardani Mutiara Kusuma ,   Universitas Katolik Widya Mandala Surabaya
Published: March 2024

Pandemi Covid-19 faktanya memang mempengaruhi sektor perekonomian, tak terkecuali usaha kecil menengah (UMKM). Di balik menurunnya pendapatan UMKM selama hampir dua bulan terakhir, namun para pelaku usaha tetap harus bertahan. Untuk memperpanjang 'usia' usaha, pelaku usaha harus memainkan strategi bisnisnya. Berikut beberapa cara atau ciri kunci sukses UMKM bertahan di tengah pandemi Covid-19.1. Lakukan Analisis SWOT. 2. Inovasi Promosi. 3. Gabung Komunitas. 4. Perencanaan Anggaran.5. Cek Persediaan Barang.Permasalahan yang ada pada warga RW 02 dan RW 03 Kelurahan Medokan Semampir Kecamatan Sukolilo Surabaya adalah warga belum pernah memainkan strategi bisnisnya. Berdasarkan permasalahan tersebut, maka tujuan utama kegiatan pengabdian masyarakat ini agar warga RW 02 dan RW 03 Kelurahan Medokan Semampir Kecamatan Sukolilo Surabaya dapat memahami strategi bisnis agar UMKM tetap produksi di tengah pandemi. Sehingga tim ABDIMAS mengembangkan pengetahuan dan keterampilan mereka, melalui diskusi interaktif mengenai strategi bisnis, dan juga dapat meningkatkan wawasan dan kemampuan dalam mengembangkan usaha kecil yang dijalankan dan bauran pemasaran khususnya menentukan harga jual produk UMKM. Harga adalah komponen yang sangat penting dari definisi bauran pemasaran. Pelaksanaan kegiatan Pengabdian Masyarakat ini dikemas dengan menggunakan metode ceramah, diskusi, pelatihan, dan pembinaan secara berkelanjutan, dengan berbagai macam kegiatan dalam hal ini warga RW 02 dan RW 03 Kelurahan Medokan Semampir Kecamatan Sukolilo Surabaya diberi kesempatan untuk dapat merencanakan dan menentukan persaingan bisnis, teori, contoh, dan jenisnya.
Effects on enzyme activity and DNA integrity in rainbow trout Oncorhynchus mykiss exposed to fish farm effluents
Authors: Alvarado-Flores CO , Carmona E , Nimptsch J , Oberti C , Vega R , Anabalón L , Encina-Montoya F
Published: March 2024

Fish farm effluents are known to affect water quality and freshwater ecosystems, potentially harming non-target organisms and ecosystem processes. We studied the effect of fish farm effluents at different concentrations (3.125-100% v/v) on catalase (CAT) and glutathione S-transferase (GST) activity as well as the DNA integrity of Oncorhynchus mykiss fry over 24-120 h. Biochemical responses and DNA damage analysis were conducted to assess the impact. We found that fish farm effluent had higher conductivity, nitrate, nitrite, and total dissolved solids concentrations downstream compared to upstream of the farm. Interestingly, no antibiotics were detected in the effluent. CAT activity significantly increased in the fish liver at concentrations of 12.5, 50, and 100% of the effluent after 72 h. In the gills, a significant increase was observed at concentrations ranging from 6.25 to 100% of the effluent after both 24 and 72 h. GST activity increased significantly in the liver at a concentration of 100% of the effluent after 72 h and in the gills at concentrations of 25, 50, and 100% after 24 h, with a decrease noted at higher concentrations. DNA damage assessment revealed significant DNA strand breaks in blood cells at concentrations of 12.5, 25, 50, and 100% of the effluent after 120 h of exposure. The results demonstrate that fish farm effluents can induce oxidative stress, causing damage to DNA integrity in blood cells. Our findings emphasize the potential ecological risks posed by fish farm effluents to aquatic organisms.
Feeding ecology of harbour porpoises Phocoena phocoena stranded on the Galician coast (NW Spain) between 1990 and 2018
Authors: Hernandez-Gonzalez A , Saavedra C , Read FL , López A , Gouveia A , Covelo P , Alonso-Fernández A , Velasco F , Begoña Santos M , Pierce GJ
Published: March 2024

Diet studies on the endangered and genetically distinct Iberian population of the southern harbour porpoise Phocoena phocoena are scarce. The present study provides updated information on the feeding ecology of this cetacean along the Galician coast (NW Spain) over the last 3 decades (1990-2018). The stomach contents of 72 stranded harbour porpoises were analysed to determine diet composition, to study which factors affect dietary variability and to estimate overlap between harbour porpoise diet and the target species of the fisheries in the study area, one of the most important fishing regions in Europe. Results showed that harbour porpoises are mainly piscivorous. We identified 33 prey taxa, but only 4 were important in the diet: fish of the genus Trisopterus, blue whiting Micromesistius poutassou, Atlantic horse mackerel Trachurus trachurus and European hake Merluccius merluccius. Interannual and ontogenetic variability in the diet were statistically significant, although differences in diet between sexes or between seasons were not detected. The diet of harbour porpoises from the Galician coast shows a partial overlap with fisheries catches in the area in terms of commercial fish species (≈61%) and size classes (≈45%), confirming the potential vulnerability of the Iberian population to interactions with fishing activities (i.e. bycatch in fishing gear and/or reduced prey availability).
Against the Implied Translator
Authors: Zhang Qian
Published: March 2024

This article calls into question the validity and necessity of the concept of the ‘implied translator’, aiming at clarifying the confusion it creates between the translational and narratological concepts of ‘translator’s voice’ and ‘narrative voice’. It suggests that some translation scholars’ concern about the translator’s textual status reflects anxiety about the disciplinary status of Translation Studies, and that in their wish to improve the situation they run the risk of a lopsided emphasis on the translator’s role, which may result in a confrontation between translation (Translation Studies) and literature (Literary Studies). Translated narrative studies based respectively on bilingual textual comparison and monolingual translated narrative analysis should, it is argued, be integrated. Meanwhile, translation scholars’ endeavours to promote the status of Translation Studies do not have to turn the translator into an interceptor who needs to usurp the author’s original voice.
Utilizing GO/PEDOT:PSS/PtNPs-enhanced high-stability microelectrode arrays for investigating epilepsy-induced striatal electrophysiology alterations
Authors: Han Meiqi , Wang Yu , Jing Luyi , Yang Gucheng , Liu Yaoyao , Mo Fan , Xu Zhaojie , Luo Jinping , Jia Qianli , Zhu Yuxin , Cao Hanwen , Cai Xinxia , Liu Juntao
Published: March 2024

The striatum plays a crucial role in studying epilepsy, as it is involved in seizure generation and modulation of brain activity. To explore the complex interplay between the striatum and epilepsy, we engineered advanced microelectrode arrays (MEAs) specifically designed for precise monitoring of striatal electrophysiological activities in rats. These observations were made during and following seizure induction, particularly three and 7 days post-initial modeling. The modification of graphene oxide (GO)/poly (3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS)/platinu-m nanoparticles (PtNPs) demonstrated a marked reduction in impedance (10.5 ± 1.1 kΩ), and maintained exceptional stability, with impedance levels remaining consistently low (23 kΩ) even 14 days post-implantation. As seizure intensity escalated, we observed a corresponding increase in neuronal firing rates and local field potential power, with a notable shift towards higher frequency peaks and augmented inter-channel correlation. Significantly, during the grand mal seizures, theta and alpha bands became the dominant frequencies in the local field potential. Compared to the normal group, the spike firing rates on day 3 and 7 post-modeling were significantly higher, accompanied by a decreased firing interval. Power in both delta and theta bands exhibited an increasing trend, correlating with the duration of epilepsy. These findings offer valuable insights into the dynamic processes of striatal neural activity during the initial and latent phases of temporal lobe epilepsy and contribute to our understanding of the neural mechanisms underpinning epilepsy.
Role of autophagy in ischemic stroke: insights from animal models and preliminary evidence in the human disease
Authors: Stanzione Rosita , Pietrangelo Donatella , Cotugno Maria , Forte Maurizio , Rubattu Speranza
Published: March 2024

Stroke represents a main cause of death and permanent disability worldwide. The molecular mechanisms underlying cerebral injury in response to the ischemic insults are not completely understood. In this article, we summarize recent evidence regarding the role of autophagy in the pathogenesis of ischemic stroke by reviewing data obtained in murine models of either transient or permanent middle cerebral artery occlusion, and in the stroke-prone spontaneously hypertensive rat. Few preliminary observational studies investigating the role of autophagy in subjects at high cerebrovascular risk and in cohorts of stroke patients were also reviewed. Autophagy plays a dual role in neuronal and vascular cells by exerting both protective and detrimental effects depending on its level, duration of stress and type of cells involved. Protective autophagy exerts adaptive mechanisms which reduce neuronal loss and promote survival. On the other hand, excessive activation of autophagy leads to neuronal cell death and increases brain injury. In conclusion, the evidence reviewed suggests that a proper manipulation of autophagy may represent an interesting strategy to either prevent or reduce brain ischemic injury.
Impact of different spacers on the conjugation between Anderson-Evans polyoxometalates and peptides
Authors: Yu Haihong , Honisch Claudia , Frigo Mattia , Balice Nicola , Tagliavini Valeria , Zhao Xue , Stramiglio Elisabetta , Campofelice Ambra , Serratì Simona , Azzariti Amalia , Porcelli Letizia , Zanetti Polzi Laura , Corni Stefano , Ruzza Paolo , Carraro Mauro
Published: March 2024

The Anderson-Evans polyoxometalates (POM) display a promising anticancer activity. The conjugation with the GRP-receptor antagonist peptide Demobesin (fQWAVGHL-NHEt) was exploited to impart cell targeting capabilities and improve the selectivity of such polyanions. However, the POM interacts with the grafted peptides, inducing chains folding and self-assembly of the resulting hybrids, thus decreasing their recognition ability. Within this context, a tailored spacer, including two domains, i.e., a hydrophilic one (1,13-diamino-4,7,10-trioxatridecan-succinamic acid, Ttds) and a tetra-anionic one (Glu-Glu-Glu-Glu-βAla, EEEE-βA) was previously utilized to mitigate such interaction. In this work, hybrid POMs containing only Ttds or EEEE-βA were prepared and the contribution of the two spacers was separately studied by using 2D NMR, fluorimetry and circular dichroism (CD). Transmission electron microscopy (TEM) was also used to observe the impact of the different spacers on self-assembly. Owing to the relevant effects observed for EEEE-βA, MD calculations were finally performed to elucidate its behavior when incorporated in the hybrid POM. Our results show that, despite the stronger impact of EEEE-βA spacer, only when both spacer are present together it is possible to observe a significant effect on the retention of peptide's secondary structure and recognition capability.
Synced ads: effects of mobile ad size and timing
Authors: Brechman Jean M. , Varan Duane , Wooley Brooke , Bellman Steven
Published: March 2024

Introduction

Synced ads differ from other forms of targeted advertising on mobile devices because they target concurrent media usage rather than location or predicted interest in the brand. For example, a TV-viewer’s smartphone could listen to the ads playing on the TV set and show matching social media ads. These social media ads could be timed to appear simultaneously with the TV ad, or shortly before or after.

Methods

This research reports a meta-analysis (N = 980) of four lab studies that used representative samples of consumers and realistic manipulations of synced ads. These studies contrasted with most previous studies of synced ads, which have used student samples and unrealistic manipulations or imagined scenarios, which means little is known about whether or why synced ads are effective in real life. These four studies manipulated the effects of synced-ad timing (simultaneous vs. sequential before or after) and the size of the mobile ad, to see if these moderate the effects of synced ads.

Results

The results showed that synced ads were more effective, measured by unaided brand recall, when they were shown after the TV commercial, rather than simultaneously. Ad size had no moderating effect, which suggests that normal ads can be used, rather than the full-screen or pop-up ads used in previous studies. A final study, in which ad timing was user-controlled, rather than advertiser-controlled, showed that precise timing is not important for synced-ad effectiveness.

Discussion

These results suggest the effects of synced ads are best explained by repetition rather than synergy between the two exposures. There were no significant effects on brand attitude, ad liking, or purchase intention. These results have implications for theoretical models of synced-ad effectiveness, and for advertisers planning to use synced ads.
Implementation of water energy food-health nexus in a climate constrained world: a review for South Africa
Authors: Mutanga Shingirirai S. , Mantlana Brian K. , Mudavanhu Shepherd , Muthige Mavhungu S. , Skhosana Felix V. , Lumsden Trevor , Naidoo Sasha , Thambiran Tirusha , John Juanette
Published: March 2024

In recent years, the Water-Energy-Food (WEF) nexus has gained significant attention in global research. Spatial inequality in water-energy-food security (WEF) and its impact on public health and how this is affected by climate change remains a grand adaptation challenge. South Africa is extremely vulnerable and exposed to the impacts of climate change due to its socio-economic and environmental context. While alternative nexus types have garnered interest, this paper pioneers an extension of the conventional WEF framework to encompass health, giving rise to the Water-Energy-Food-Health (WEF-H) nexus. Despite a plethora of WEF nexus studies focused on South Africa, a substantial knowledge gap persists due to the lack of a comprehensive overview of the enablers and barriers to realizing the WEF-H nexus. South Africa boasts diverse policies related to water, energy, food, and health; however, their alignment remains an ongoing challenge. This study seeks to bridge this critical gap by conducting an exhaustive review of existing literature. Its primary aim is to delve into the intricate mechanisms that either facilitate or impede the actualization of the WEF-H nexus in South Africa. By synthesizing insights from a wide array of literature sources, this research strives to illuminate the challenges and opportunities stemming from the integration of health considerations into the established WEF nexus framework. This exploration holds immense significance, not only for unraveling the multifaceted interactions between these pivotal sectors but also for guiding policy development and decision-making processes in South Africa towards a more holistic and sustainable approach to resource management.
Temporal analysis of the state of the Gbele Resource Reserve in the Upper West Region, Ghana
Authors: Aabeyir Raymond , Peprah Kenneth , Amponsah Amos
Published: March 2024

Introduction

This paper assessed the changes in the forest cover of the Gbele Resource Reserve from 1990 to 2020. This provides a basis for strengthening management decisions to protect the resources in the Gbele Resource Reserve effectively.

Methods

Landsat images for 1990, 2000, 2010 and 2020 were obtained from the United States Geological Service site. They were processed and classified in the System for Earth Observation Data Access, Processing, & Analysis for Land Monitoring (SEPAL), a web-based cloud computing platform. The accuracy of the images was assessed using 50 ground-truth points obtained from the 3-5 meter spatial and near-daily temporal resolution planet satellite images from Norway’s International Climate and Forest Initiative (NICFI). Post classification change detection was used to analyse the changes in land cover from 1990 to 2000, 2000 to 2010 and from 2010 to 2020.

Results

The analysis revealed that the total forest area was 55273.2 ha. In 1990, 74.9 % of the reserve was open forest and 24.6 % was shrubs/grass. The open forest declined to 65.8 % in 2000 and further to 62.4 % in 2010 while the shrubs/grass cover increased to 35.7 in 2010. As of 2020, the forest increased to 73.6 % while the shrub/grass cover declined to 25.8 %.

Discussion

These changes could be attributed partly to widespread charcoal production in the fringe districts and rose wood harvesting in the early 2000s. charcoal production and rosewood logging have been livelihood sources for fringe communities. The ban on the harvest and exportation of rosewood after 2010 could partly explain the sharp increase in the open forest cover from 2010 to 2020. The changes in the extent of the reserve from 1990 to 2020 revealed that the reserve can vulnerable to excessive exploitation and can also be resilient if deliberate efforts are made to protect it. It is recommended that the fringe district and municipal Assemblies should strengthen the enforcement of the ban on the logging of the rosewood and trees in the reserve for the production of charcoal.
Non-invasive prediction for pathologic complete response to neoadjuvant chemoimmunotherapy in lung cancer using CT-based deep learning: a multicenter study
Authors: Qu Wendong , Chen Cheng , Cai Chuang , Gong Ming , Luo Qian , Song Yongxiang , Yang Minglei , Shi Min
Published: March 2024

Neoadjuvant chemoimmunotherapy has revolutionized the therapeutic strategy for non-small cell lung cancer (NSCLC), and identifying candidates likely responding to this advanced treatment is of important clinical significance. The current multi-institutional study aims to develop a deep learning model to predict pathologic complete response (pCR) to neoadjuvant immunotherapy in NSCLC based on computed tomography (CT) imaging and further prob the biologic foundation of the proposed deep learning signature. A total of 248 participants administrated with neoadjuvant immunotherapy followed by surgery for NSCLC at Ruijin Hospital, Ningbo Hwamei Hospital, and Affiliated Hospital of Zunyi Medical University from January 2019 to September 2023 were enrolled. The imaging data within 2 weeks prior to neoadjuvant chemoimmunotherapy were retrospectively extracted. Patients from Ruijin Hospital were grouped as the training set (n = 104) and the validation set (n = 69) at the 6:4 ratio, and other participants from Ningbo Hwamei Hospital and Affiliated Hospital of Zunyi Medical University served as an external cohort (n = 75). For the entire population, pCR was obtained in 29.4% (n = 73) of cases. The areas under the curve (AUCs) of our deep learning signature for pCR prediction were 0.775 (95% confidence interval [CI]: 0.649 - 0.901) and 0.743 (95% CI: 0.618 - 0.869) in the validation set and the external cohort, significantly superior than 0.579 (95% CI: 0.468 - 0.689) and 0.569 (95% CI: 0.454 - 0.683) of the clinical model. Furthermore, higher deep learning scores correlated to the upregulation for pathways of cell metabolism and more antitumor immune infiltration in microenvironment. Our developed deep learning model is capable of predicting pCR to neoadjuvant chemoimmunotherapy in patients with NSCLC.
Generation and characterization of antagonistic anti-human CD39 nanobodies
Authors: Menzel Stephan , Duan Yinghui , Hambach Julia , Albrecht Birte , Wendt-Cousin Dorte , Winzer Riekje , Tolosa Eva , Rissiek Anne , Guse Andreas H. , Haag Friedrich , Magnus Tim , Koch-Nolte Friedrich , Rissiek Björn
Published: March 2024

CD39 is the major enzyme controlling the levels of extracellular adenosine triphosphate (ATP) via the stepwise hydrolysis of ATP to adenosine diphosphate (ADP) and adenosine monophosphate (AMP). As extracellular ATP is a strong promoter of inflammation, monoclonal antibodies (mAbs) blocking CD39 are utilized therapeutically in the field of immune-oncology. Though anti-CD39 mAbs are highly specific for their target, they lack deep penetration into the dense tissue of solid tumors, due to their large size. To overcome this limitation, we generated and characterized nanobodies that targeted and blocked human CD39. From cDNA-immunized alpacas we selected 16 clones from seven nanobody families that bind to two distinct epitopes of human CD39. Among these, clone SB24 inhibited the enzymatic activity of CD39. Of note, SB24 blocked ATP degradation by both soluble and cell surface CD39 as a 15kD monomeric nanobody. Dimerization via fusion to an immunoglobulin Fc portion further increased the blocking potency of SB24 on CD39-transfected HEK cells. Finally, we confirmed the CD39 blocking properties of SB24 on human PBMCs. In summary, SB24 provides a new small biological antagonist of human CD39 with potential application in cancer therapy.
Evaluating an obstetrics and gynecology teaching program for medical students incorporating simulation-based education underpinned by cognitive load theory
Authors: Atiomo William , Ennab Farah , Stanley Adrian , Ezimokhai Mutairu
Published: March 2024

Although there have been previous publications on curriculum innovations in teaching O&G to medical students, especially utilizing simulation-based education, there have been none, as far as we know, incorporating and evaluating the outcomes using cognitive load theory. The aim of this article was to describe the introduction, implementation, and evaluation of an innovative teaching program in O&G, incorporating simulation-based education, underpinned by cognitive load theory. Cognitive load is defined as the amount of information a working memory can hold at any one time and incorporates three types of cognitive load—intrinsic, extraneous, and germane. To optimize learning, educators are encouraged to manage intrinsic cognitive load, minimize extraneous cognitive load, and promote germane cognitive load. In these sessions, students were encouraged to prepare in advance of each session with recommended reading materials; to limit intrinsic cognitive load and promote germane cognitive load, faculty were advised ahead of each session to manage intrinsic cognitive load, an open-book MCQ practice session aimed to reduce anxiety, promote psychological safety, and minimize extraneous cognitive load. For the simulation sessions, the faculty initially demonstrated the role-play situation or clinical skill first, to manage intrinsic cognitive load and reduce extraneous cognitive load. The results of the evaluation showed that the students perceived that they invested relatively low mental effort in understanding the topics, theories, concepts, and definitions discussed during the sessions. There was a low extraneous cognitive load. Measures of germane cognitive load or self-perceived learning were high. The primary message is that we believe this teaching program is a model that other medical schools globally might want to consider adopting, to evaluate and justify innovations in the teaching of O&G to medical students. The secondary message is that evaluation of innovations to teaching and facilitation of learning using cognitive load theory is one way to contribute to the high-quality training of competent future healthcare workers required to provide the highest standard of care to women who are crucial to the overall health and wellbeing of a nation.
Interplay of cytokines in the pathophysiology of atopic dermatitis: insights from Murin models and human
Authors: Yamamura Yuto , Nakashima Chisa , Otsuka Atsushi
Published: March 2024

The pathogenesis of atopic dermatitis (AD) is understood to be crucially influenced by three main factors: dysregulation of the immune response, barrier dysfunction, and pruritus. In the lesional skin of AD, various innate immune cells, including Th2 cells, type 2 innate lymphoid cells (ILC2s), and basophils, produce Th2 cytokines [interleukin (IL)-4, IL-5, IL-13, IL-31]. Alarmins such as TSLP, IL-25, and IL-33 are also produced by epidermal keratinocytes, amplifying type 2 inflammation. In the chronic phase, not only Th2 cells but also Th22 and Th17 cells increase in number, leading to suppression of filaggrin expression by IL-4, IL-13, and IL-22, which further deteriorates the epidermal barrier function. Dupilumab, which targets IL-4 and IL-13, has shown efficacy in treating moderate to severe AD. Nemolizumab, targeting IL-31RA, effectively reduces pruritus in AD patients. In addition, clinical trials with fezakinumab, targeting IL-22, have demonstrated promising results, particularly in severe AD cases. Conversely, in murine models of AD, several cytokines, initially regarded as promising therapeutic targets, have not demonstrated sufficient efficacy in clinical trials. IL-33 has been identified as a potent activator of immune cells, exacerbating AD in murine models and correlating with disease severity in human patients. However, treatments targeting IL-33 have not shown sufficient efficacy in clinical trials. Similarly, thymic stromal lymphopoietin (TSLP), integral to type 2 immune responses, induces dermatitis in animal models and is elevated in human AD, yet clinical treatments like tezepelumab exhibit limited efficacy. Therapies targeting IL-1α, IL-5, and IL-17 also failed to achieve sufficient efficacy in clinical trials. It has become clear that for treating AD, IL-4, IL-13, and IL-31 are relevant therapeutic targets during the acute phase, while IL-22 emerges as a target in more severe cases. This delineation underscores the necessity of considering distinct pathophysiological aspects and therapeutic targets in AD between mouse models and humans. Consequently, this review delineates the distinct roles of cytokines in the pathogenesis of AD, juxtaposing their significance in human AD from clinical trials against insights gleaned from AD mouse models. This approach will improve our understanding of interspecies variation and facilitate a deeper insight into the pathogenesis of AD in humans.
Mechanisms of ferroptosis in nonalcoholic fatty liver disease and therapeutic effects of traditional Chinese medicine: a review
Authors: Wang Nan , Que Hanyun , Luo Qiulin , Zheng Wenxin , Li Hong , Wang Qin , Gu Jian
Published: March 2024

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in hepatocytes (nonalcoholic fatty liver (NAFL)), and lobular inflammation and hepatocyte damage (which characterize nonalcoholic steatohepatitis (NASH) are found in most patients). A subset of patients will gradually develop liver fibrosis, cirrhosis, and eventually hepatocellular carcinoma, which is a deadly disease that threatens human life worldwide. Ferroptosis, a novel nonapoptotic form of programmed cell death (PCD) characterized by iron-dependent accumulation of reactive oxygen radicals and lipid peroxides, is closely related to NAFLD. Traditional Chinese medicine (TCM) has unique advantages in the prevention and treatment of NAFLD due to its multicomponent, multipathway and multitarget characteristics. In this review, we discuss the effect of TCM on NAFLD by regulating ferroptosis, in order to provide reference for the further development and application of therapeutic drugs to treat NAFLD.
Artificial intelligence in routine blood tests
Authors: Santos-Silva Miguel A. , Sousa Nuno , Sousa João Carlos
Published: March 2024

Routine blood tests drive diagnosis, prognosis, and monitoring in traditional clinical decision support systems. As a routine diagnostic tool with standardized laboratory workflows, clinical blood analysis offers superior accessibility to a comprehensive assessment of physiological parameters. These parameters can be integrated and automated at scale, allowing for in-depth clinical inference and cost-effectiveness compared to other modalities such as imaging, genetic testing, or histopathology. Herein, we extensively review the analytical value of routine blood tests leveraged by artificial intelligence (AI), using the ICD-10 classification as a reference. A significant gap exists between standard disease-associated features and those selected by machine learning models. This suggests an amount of non-perceived information in traditional decision support systems that AI could leverage with improved performance metrics. Nonetheless, AI-derived support for clinical decisions must still be harmonized regarding external validation studies, regulatory approvals, and clinical deployment strategies. Still, as we discuss, the path is drawn for the future application of scalable artificial intelligence (AI) to enhance, extract, and classify patterns potentially correlated with pathological states with restricted limitations in terms of bias and representativeness.
Deletion of the Mycobacterium tuberculosis cyp138 gene leads to changes in membrane-related lipid composition and antibiotic susceptibility
Authors: Lu Yun , Chen Hongtong , Shao Zhiyuan , Sun Lang , Li Congran , Lu Yu , You Xuefu , Yang Xinyi
Published: March 2024

Introduction

Mycobacterium tuberculosis (Mtb), the main cause of tuberculosis (TB), has brought a great burden to the world's public health. With the widespread use of Mtb drug-resistant strains, the pressure on anti-TB treatment is increasing. Anti-TB drugs with novel structures and targets are urgently needed. Previous studies have revealed a series of CYPs with important roles in the survival and metabolism of Mtb. However, there is little research on the structure and function of CYP138.

Methods

In our study, to discover the function and targetability of CYP138, a cyp138-knockout strain was built, and the function of CYP138 was speculated by the comparison between cyp138-knockout and wild-type strains through growth curves, growth status under different carbon sources, infection curves, SEM, MIC tests, quantitative proteomics, and lipidomics.

Results and discussion

The knockout of cyp138 was proven to affect the Mtb's macrophage infection, antibiotics susceptibility, and the levels of fatty acid metabolism, membrane-related proteins, and lipids such as triacylglycerol. We proposed that CYP138 plays an important role in the synthesis and decomposition of lipids related to the cell membrane structure as a new potential anti-tuberculosis drug target.
Important soil microbiota's effects on plants and soils: a comprehensive 30-year systematic literature review
Authors: Wang Xueling , Chi Yongkuan , Song Shuzhen
Published: March 2024

Clarifying the relationship between soil microorganisms and the plant-soil system is crucial for encouraging the sustainable development of ecosystems, as soil microorganisms serve a variety of functional roles in the plant-soil system. In this work, the influence mechanisms of significant soil microbial groups on the plant-soil system and their applications in environmental remediation over the previous 30 years were reviewed using a systematic literature review (SLR) methodology. The findings demonstrated that: (1) There has been a general upward trend in the number of publications on significant microorganisms, including bacteria, fungi, and archaea. (2) Bacteria and fungi influence soil development and plant growth through organic matter decomposition, nitrogen, phosphorus, and potassium element dissolution, symbiotic relationships, plant growth hormone production, pathogen inhibition, and plant resistance induction. Archaea aid in the growth of plants by breaking down low-molecular-weight organic matter, participating in element cycles, producing plant growth hormones, and suppressing infections. (3) Microorganism principles are utilized in soil remediation, biofertilizer production, denitrification, and phosphorus removal, effectively reducing environmental pollution, preventing soil pathogen invasion, protecting vegetation health, and promoting plant growth. The three important microbial groups collectively regulate the plant-soil ecosystem and help maintain its relative stability. This work systematically summarizes the principles of important microbial groups influence plant-soil systems, providing a theoretical reference for how to control soil microbes in order to restore damaged ecosystems and enhance ecosystem resilience in the future.
Interaction of bacteriophage P1 with an epiphytic Pantoea agglomerans strain—the role of the interplay between various mobilome elements
Authors: Giermasińska-Buczek Katarzyna , Gawor Jan , Stefańczyk Emil , Gągała Urszula , Żuchniewicz Karolina , Rekosz-Burlaga Hanna , Gromadka Robert , Łobocka Małgorzata
Published: March 2024

P1 is a model, temperate bacteriophage of the 94 kb genome. It can lysogenize representatives of the Enterobacterales order. In lysogens, it is maintained as a plasmid. We tested P1 interactions with the biocontrol P. agglomerans L15 strain to explore the utility of P1 in P. agglomerans genome engineering. A P1 derivative carrying the Tn9 (cmR) transposon could transfer a plasmid from Escherichia coli to the L15 cells. The L15 cells infected with this derivative formed chloramphenicol-resistant colonies. They could grow in a liquid medium with chloramphenicol after adaptation and did not contain prophage P1 but the chromosomally inserted cmR marker of P1 Tn9 (cat). The insertions were accompanied by various rearrangements upstream of the Tn9 cat gene promoter and the loss of IS1 (IS1L) from the corresponding region. Sequence analysis of the L15 strain genome revealed a chromosome and three plasmids of 0.58, 0.18, and 0.07 Mb. The largest and the smallest plasmid appeared to encode partition and replication incompatibility determinants similar to those of prophage P1, respectively. In the L15 derivatives cured of the largest plasmid, P1 with Tn9 could not replace the smallest plasmid even if selected. However, it could replace the smallest and the largest plasmid of L15 if its Tn9 IS1L sequence driving the Tn9 mobility was inactivated or if it was enriched with an immobile kanamycin resistance marker. Moreover, it could develop lytically in the L15 derivatives cured of both these plasmids. Clearly, under conditions of selection for P1, the mobility of the P1 selective marker determines whether or not the incoming P1 can outcompete the incompatible L15 resident plasmids. Our results demonstrate that P. agglomerans can serve as a host for bacteriophage P1 and can be engineered with the help of this phage. They also provide an example of how antibiotics can modify the outcome of horizontal gene transfer in natural environments. Numerous plasmids of Pantoea strains appear to contain determinants of replication or partition incompatibility with P1. Therefore, P1 with an immobile selective marker may be a tool of choice in curing these strains from the respective plasmids to facilitate their functional analysis.
Cross-validation of chemical and genetic disruption approaches to inform host cellular effects on Wolbachia abundance in Drosophila
Authors: Sharmin Zinat , Samarah Hani , Aldaya Bourricaudy Rafael , Ochoa Laura , Serbus Laura Renee
Published: March 2024

Introduction

Endosymbiotic Wolbachia bacteria are widespread in nature, present in half of all insect species. The success of Wolbachia is supported by a commensal lifestyle. Unlike bacterial pathogens that overreplicate and harm host cells, Wolbachia infections have a relatively innocuous intracellular lifestyle. This raises important questions about how Wolbachia infection is regulated. Little is known about how Wolbachia abundance is controlled at an organismal scale.

Methods

This study demonstrates methodology for rigorous identification of cellular processes that affect whole-body Wolbachia abundance, as indicated by absolute counts of the Wolbachia surface protein (wsp) gene.

Results

Candidate pathways, associated with well-described infection scenarios, were identified. Wolbachia-infected fruit flies were exposed to small molecule inhibitors known for targeting those same pathways. Sequential tests in D. melanogaster and D. simulans yielded a subset of chemical inhibitors that significantly affected whole-body Wolbachia abundance, including the Wnt pathway disruptor, IWR-1 and the mTOR pathway inhibitor, Rapamycin. The implicated pathways were genetically retested for effects in D. melanogaster, using inducible RNAi expression driven by constitutive as well as chemically-induced somatic GAL4 expression. Genetic disruptions of armadillo, tor, and ATG6 significantly affected whole-body Wolbachia abundance.

Discussion

As such, the data corroborate reagent targeting and pathway relevance to whole-body Wolbachia infection. The results also implicate Wnt and mTOR regulation of autophagy as important for regulation of Wolbachia titer.
Uncovering the diversity of pathogenic invaders: insights into protozoa, fungi, and worm infections
Authors: Shukla Richa , Soni Jyoti , Kumar Ashish , Pandey Rajesh
Published: March 2024

Post COVID-19, there has been renewed interest in understanding the pathogens challenging the human health and evaluate our preparedness towards dealing with health challenges in future. In this endeavour, it is not only the bacteria and the viruses, but a greater community of pathogens. Such pathogenic microorganisms, include protozoa, fungi and worms, which establish a distinct variety of disease-causing agents with the capability to impact the host’s well-being as well as the equity of ecosystem. This review summarises the peculiar characteristics and pathogenic mechanisms utilized by these disease-causing organisms. It features their role in causing infection in the concerned host and emphasizes the need for further research. Understanding the layers of pathogenesis encompassing the concerned infectious microbes will help expand targeted inferences with relation to the cause of the infection. This would strengthen and augment benefit to the host’s health along with the maintenance of ecosystem network, exhibiting host-pathogen interaction cycle. This would be key to discover the layers underlying differential disease severities in response to similar/same pathogen infection.
Integrated 16S rRNA sequencing and metagenomics insights into microbial dysbiosis and distinct virulence factors in inflammatory bowel disease
Authors: Wang Haijing , Wang Yuanjun , Yang Libin , Feng Jiawen , Tian Shou , Chen Lingyan , Huang Wei , Liu Jia , Wang Xiaojin
Published: March 2024

Introduction

The escalation of urbanization correlates with rising rates of inflammatory bowel disease (IBD), necessitating research into new etiological factors. This study aims to elucidate the gut microbiota profiles in IBD patients and compare them with healthy controls in a western city of China.

Methods

We conducted a multicenter case-control study from the end of 2020, using 16S rRNA gene sequencing (n = 36) and metagenomic sequencing (n = 12) to analyze the gut microbiota of newly diagnosed IBD patients, including those with Crohn's disease (CD) and ulcerative colitis (UC).

Results

Our results demonstrated a significant enrichment of the phylum Proteobacteria, particularly the genus Escherichia-Shigella, in CD patients. Conversely, the genus Enterococcus was markedly increased in UC patients. The core gut microbiota, such as the Christensenellaceae R-7 group, Fusicatenibacter, and Holdemanella, were primarily identified in healthy subjects. Additionally, significant interactions between the microbiome and virulence factors were observed.

Discussion

The findings suggest that oxidative stress may play a pivotal role in the pathology of IBD. This study contributes to the growing dialogue about the impact of gut microbiota on the development of IBD and its variations across different geographies, highlighting potential avenues for further research.
Irreversible atrophy in memory brain regions over 7 years is predicted by glycemic control in type 2 diabetes without mild cognitive impairment
Authors: Canário Nádia , Crisóstomo Joana , Duarte João Valente , Moreno Carolina , Quental Hugo , Gomes Leonor , Oliveira Francisco , Castelo-Branco Miguel
Published: March 2024

Memory-related impairments in type 2 diabetes may be mediated by insulin resistance and hyperglycemia. Previous cross-sectional studies have controversially suggested a relationship between metabolic control and a decrease in hippocampal volumes, but only longitudinal studies can test this hypothesis directly. We performed a longitudinal morphometric study to provide a direct test of a possible role of higher levels of glycated hemoglobin with long term brain structural integrity in key regions of the memory system – hippocampus, parahippocampal gyrus and fusiform gyrus. Grey matter volume was measured at two different times – baseline and after ~7 years. We found an association between higher initial levels of HbA1C and grey matter volume loss in all three core memory regions, even in the absence of mild cognitive impairment. Importantly, these neural effects persisted in spite of the fact that patients had significantly improved their glycemic control. This suggests that early high levels of HbA1c might be irreversibly associated with subsequent long-term atrophy in the medial temporal cortex and that early intensive management is critical.