bluuebunny/crossref_metadata_2025 huggingface dataset:
STRUKTUR DAN KOMPOSISI VEGETASI DI KAWASAN HUTAN RAKYAT DUSUN MURPAYUNG DESA SIGAR PENJALIN KABUPATEN LOMBOK UTARA
Authors: Sumantra I Wayan , Rita Raden Roro Narwastu Dwi
Published: July 2024

Tujuan yang ingin dicapai dalam penelitian ini yaitu mengetahui Indeks Nilai Penting (INP) dan Indeks Keanekaragaman Jenis (H’) vegetasi di kawasan Hutan Rakyat pada Kelompok Tani Hutan Beriuk Patuh Dusun Murpayung Desa Sigar Penjalin Kecamatan Tanjung Kabupaten Lombok Utara. Metode penelitian yang digunakan dalam penelitian ini adalah metode deskriptif kuantitatif, dengan pengambilan data menggunakan metode Garis berpetak yang merupakan modifikasi dari petak ganda atau cara jalur. Hasil penelitian yang diperoleh menunjukkan bahwa untuk tingkat pohon dengan jumlah vegetasi yang ditemukan sebanyak 58 jenis, INP tertinggi berturut-turut adalah Kelapa 49,18%, Mente 30,78%, Ulam 20,65%,Udu/Kalimuru 19,13%, dan Gmelina 16,14%. Pada tingkat tiang terdapat 45 jenis dengan INP tertinggi Gmelina 114,15%, Mente 38,00%, Ulam 17,40%,Pinang 12,63%, dan Mahoni 11,18%. Untuk tingkat pancang ditemukan 41 jenis dengan INP tertinggi adalah Gmelina 72,0%, Mahoni 24,3%, Ulam 17,3%, Mangga Hutan 13,8%, dan Mente 8,7%. Dan untuk tingkat semai ditemukan 40 jenis dengan INP tertinggi berturut-turut adalah Ulam 47,8%, Gmelina 21,2%, Mangga Hutan 18,0%, Putat 11,7%, dan Kumbi 10,6%. Sedangkan untuk nilai Indeks Keanekaragaman Jenis (H’) untuk tingkat pohon adalah 3,16 yang berarti tinggi yang menunjukkan bahwa ekosistem di kawasan Hutan Rakyat tersebut adalah baik. Untuk tingkat tiang H’ adalah 2,275, tingkat pancang H’ 2,094, dan tingkat semai H’ 2,692, yang berarti bahwa keanekaragaman jenis pada masing-masing tingkat tersebut adalah sedang.
IDENTIFIKASI JENIS DAN PEMANFAATAN BAMBU DI DESA REMBITAN KECAMATAN PUJUT KABUPATEN LOMBOK TENGAH
Authors: Lembusora Lembusora , Ratnaningsih Yulia
Published: July 2024

Masyarakat desa Rambitan telah lama memanfaatkan tanaman bambu yang tumbuh disekitar wilayah mereka. Akan tetapi sebagian warga masyarakat Desa Rembitan masih ada yang belum mengetahui seberapa banyak jenis serta pemanfaatan dari bambu tersebut. oleh karena itu penelitian ini bertujuan untuk melakukan identifikasi jenis dan pemanfaatan bambu di desa Rambitan. Penelitian ini merupakan penelitian deskriptif. Data yang digunakan meliputi data primer dan sekunder. Teknik pengambilan sampel yang digunakan adalah teknik Snowball sampling. Ditemukan 8 jenis bambu di Desa Rembitan, Kecamatan Pujut, Kabupaten Lombok Tengah, jenis bambu tersebut yaitu : bambu petung (Dendrocalamus asper) , bambu ampel (Bambusa vulgaris), bambu tamiang (Schizostachyum brachycladum), bambu kuning  (Bambusa vulgaris schard ), bambu tali (Gigantochloa apus),  bambu tutul (Bambusa maculata),  bambu tulup (Bambusa multiplex), dan bambu duri (Bambusa blumeana ). Masyarakat Desa Rembitan memanfaatkan bambu untuk pagar, berugak/ lasah, tiang antena, bahan bangunan, staiger, tangga, kandang sapi, kandang ayam, bethek, kurungan ayam, lantai dinding, hiasan rumah, mengambil rebungnya sebagai sayuran dan memanfaatkan daunya sebagai pembungkus nasi, sebagai alat pencuci panci dan digunakan untuk pemotongan hewan. Berdasarkan hasil penelitian tersebut terdapat 3 (tiga) pola pemasaran bambu yaitu: pengambil dan pengguna langsung, pengepul atau pedagang bambu dan pembeli atau pengguna bambu.
MINI-REVIEW UJI HEDONIK PADA PRODUK TEH HERBAL HUTAN
Authors: Triandini I Gusti Agung Ayu Hari , Wangiyana I Gde Adi Suryawan
Published: July 2024

Teh herbal hutan adalah produk teh herbal jenis baru yang diproduksi dari tanaman yang di lahan hutan. Tanaman yang menjadi bahan baku produk ini bervariasi mulai dari tanaman habitus pohon hingga tanaman herba yang hidup dibawah kanopi hutan. Sebagai produk minuman yang relatif baru, riset mengenai penerimaan konsumen terhadap produk ini penting untuk dilakukan melalui uji hedonik. Uji hedonik pada teh herbal hutan menggunakan skala pengukuran yang disebut skala hedonik dengan tingkat bervariasi yaitu skala 3 (suka (3), netral (2), tidak suka (1)), skala 5 (sangat suka (5), suka (4), cukup suka (3), tidak suka (2), sangat tidak suka (1), skala 7 (sangat suka (7), suka (6), agak suka (5), netral (4), sedikit tidak suka (3), tidak suka (2), sangat tidak suka (1), dan skala 9 (sangat suka sekali (9), sangat suka (8), agak suka (7), sedikit suka (6), netral (5), sedikit tidak suka (4), agak tidak suka (3), Sangat tidak suka (2), Sangat tidak suka sekali (1). Uji hedonik skala 5 merupakan metode yang paling banyak digunakan untuk mengukur tingkat kesukaan konsumen terhadap produk teh herbal hutan. Skala hedonik ini relatif sederhana namun cukup sensitif dalam mendeteksi penilaian konsumen.
PERSEPSI PENGUNJUNG TERHADAP PENGEMBANGAN OBYEK WISATA ALAM AIR TERJUN BIDADARI DI DESA KAWINDA TO’I KECAMATAN TAMBORA KABUPATEN BIMA, PROVINSI NUSA TENGGARA BARAT
Authors: Andri Andri , Masrilurrahman L L Suhirsan
Published: July 2024

Air terjun Bidadari terletak di Desa Kawinda To’i, Kecamatan Tambora Kabupaten Bima Provinsi Nusa Tenggara Barat. Penelitian ini bertujuan untuk mengetahui persepsi pengunjung terhadap pengembangan objek wisata alam air terjun Bidadaridalam penilaian akses wisata dan kondisi fasilitas objek wisata tersebut.. Metode yang digunakan dalam penelitian ini adalah metode deskritif kuantitatif. Data primer didapatkan melalui teknik observasi serta mewawancarai responden dengan menggunakan kuesioner 100 orang pengunjung. Dalam penelitian ini data dianalisis menggunakan pengukuran skala likert. Pengukuran komponen penilaian pada skala likert yaitu mencakup rentang nilai ≤ 5 diartikan sangat baik, rentang nilai 4 ≤ 4,5 diartikan baik, rentang 3 ≤ 3,5 diartikan cukup, rentang 2 ≤ 2,5 diartikan kurang baik, dan rentang ≥ 1 diartikan tidak baik. Berdasarkan penelitian persepsi pengunjung terhadap kondisi aksesbilitas wisata (3,6) dan masuk dalam kategori baik, penilaian pada kondisi kebersihan (3,6) masuk kategori baik, penilaian pada kondisi infrastruktur (3,3) masuk ke dalam kategori cukup, penilaian pada kondisi fisik (3,6) masuk ke dalam kategori baik, serta pada penilaian kepuasan pengunjung terhadap obyek wisata (4,1) masuk dalam kategori baik.. Hal ini menunjukkan bahwa perlu adanya peningkatan dalam bidang infrastruktur berupa peningkatan jaringan komunikasi serta sarana dan prasarana wisata sebagai upaya pengembangan suatu objek wisata yang dapat dilakukan dengan strategi yang baik dan tersusun, hal itu dilakukan agar dapat meningkatkan minat kunjungan di objek wisata tersebut.
Tunisian Literature and the Language Question: The Long View of a Recurring Debate
Authors: Omri Mohamed-Salah
Published: July 2024

This paper traces the life and afterlife of Tunisia's literary avant-garde ( al-tali’a al-adabiyya), which thrived between 1968 and 1972. Al-tali’a sought to ‘revolutionize’ literary language and to root Tunisian literature in the multilingual environment and social reality of the country, at a crucial period of social and political change and against the backdrop of a Leftist turn in local dissident politics. Al-tali’a sought to complete the process of language and literary decolonization in intersection with key global tendencies, including Tiermondisme and decoloniality. The language question was articulated, then as in post-2011 Tunisia, in terms of democracy and justice. While the state promoted fostering Tunisianness as state policy, there were other takes on this concept that were progressive, more deeply decolonial and justice-driven. This paper uncovers the genesis of the movement through the work of Izzeddine al-Madani in drama and Tahar Hammami, among others, in fiction and poetry.
PELATIHAN ALAT PEMADAM API RINGAN DAN KARUNG GONI SEBAGAI MEDIA PEMADAMAN KEBAKARAN KEPADA MAHASISWA POLIBATAM, SISWA DAN GURU SMK DI BATAM
Authors: Wirawan Adhitomo , Mochtoha Himawan , Zainuddin Muhammad , Irsutami Irsutami , Fajrin Aulia , Akhnedi Andre , Russel Felix , Yessica Vinda , Ramadini Putri , Halim Shakila Lulu Fadillah , Budiman Budiman
Published: July 2024

Fire disaster is one of the many disasters that occur in the wider community both in the office and residential environment. This fire disaster generally occurs due to human factors such as: using electrical loads that exceed the power capacity and placing flammable items near the source of fire. This fire hazard will be easier to overcome if people know how to put out fires properly and know how to use extinguishers such as APAR (Light Fire Extinguisher) and the use of gunny sacks. APAR is generally categorized into 3 types, namely: Dry Chemical Extinguisher, Carbon Dioxide (CO2) Extinguisher, and Foam.  Extinguishers containing dry chemical powder are very commonly used because they are able to extinguish almost all types of fires. The use of APAR is most likely to be used because of its portable nature, easy maintenance, and easy to use. In the community service that has been carried out at Batam State Polytechnic, a demonstration on how to extinguish fire with fire extinguisher and the use of gunny sacks was also carried out. Participants of this community service program are students, vocational school students and vocational school teachers.
PROSES DAN HAMBATAN DALAM PENULISAN KONTEN DI SITUS WEB OLEH AGENSI PERIKLANAN DIGITAL
Authors: Imran Maharani
Published: July 2024

Digital advertising agencies help brand owners manage and promote the brand over the internet so that the brand can persist and win the hearts of consumers by following trends or times. Content writers are needed to creatively shape ideas and concepts for a content to attract attention and influence the target audience. The purpose of this study is to describe the process and barriers of website content writing by digital advertising agencies. This study uses qualitative methods with a case study approach, data collection techniques using interviews, the data analysis techniques used in this study are thematic analysis. The outcome of this study is the process of writing website content by digital advertising agencies, consisting of obtaining keywords for articles from the management, collecting reference materials for articles related to the given keywords of articles, rewriting article content into new article content, paraphrasing the words in the article according to the received article keywords, checking articles using plagiarism checking software, sending article content to leaders and administrators for editing and for additional information in the form of interesting images related to the content of the created article, and uploading and publishing the articles on the website. From the results of this study, it is suggested that in the future, the keywords for the articles should be more diverse, the existing internet connection should be further improved, and the deadline for writing the website content should be weekly rather than daily.
Bifidobacterium animalis subsp. lactis HN019 live probiotics and postbiotics: production strategies and bioactivity evaluation for potential therapeutic properties
Authors: D’ambrosio Sergio , Dabous Azza , Sadiq Saba , Casillo Angela , Schiraldi Chiara , Cassese Elisabetta , Bedini Emiliano , Corsaro Maria Michela , Cimini Donatella
Published: July 2024

Introduction:B. animalis subsp. lactis HN019 is a commercially available well-characterized probiotic with documented effects on human health, such as the ability to enhance the immune function and to balance the intestinal microbiome. Therefore, optimizing the manufacturing process to improve sustainability, increasing biomass yields and viability, and avoiding animal -derived nutrients in the medium to meet vegan consumer’s needs, is currently of interest. Besides the established use of live probiotic cells, alternative supplements indicated as postbiotics, like non-viable cells and/or probiotics derived bioactive molecules might be considered as potential next generation biotherapeutics. In fact, advantages of postbiotics include fewer technological limitations, such as easier production processes and scale-up, and even higher specificity.

Methods: In this work, medium design together with different fermentation strategies such as batch, fed-batch and in situ product removal on lab-scale bioreactors were combined. Medium pretreatment by ultrafiltration and protease digestion was performed to reduce polysaccharidic contaminants and facilitate the purification of secreted exopolysaccharides (EPS). The latter were isolated from the fermentation broth and characterized through NMR, GC-MS and SEC-TDA analyses. The expression of TLR-4, NF-kb and IL-6 in LPS challenged differentiated CaCo-2 cells treated with EPS, live and heat-killed B. lactis cells/broth, was evaluated in vitro by western blotting and ELISA. Zonulin was also assessed by immunofluorescence assays.

Results and Discussion: The titer of viable B. lactis HN019 was increased up to 2.9 ± 0.1 x 1010 on an animal-free semidefined medium by applying an ISPR fermentation strategy. Medium pre-treatment and a simple downstream procedure enriched the representativity of the EPS recovered (87%), the composition of which revealed the presence of mannuronic acid among other sugars typically present in polysaccharides produced by bifidobacteria. The isolated EPS, live cells and whole heat inactivated broth were compared for the first up to date for their immunomodulatory and anti-inflammatory properties and for their ability to promote intestinal barrier integrity. Interestingly, EPS and live cells samples demonstrated immune-stimulating properties by downregulating the expression of TLR-4 and NF-kb, and the ability to promote restoring the integrity of the intestinal barrier by up-regulating the expression of zonulin, one of the tight junctions forming proteins. Postbiotics in the form of heat killed broth only reduced NF-kb expression, whereas they did not seem effective in the other tested conditions.
Insulin-like growth factor-binding protein 7 (IGFBP7): A microenvironment-dependent regulator of angiogenesis and vascular remodeling
Authors: Lit Kwok Keung , Zhirenova Zhamilya , Blocki Anna
Published: July 2024

Insulin-like Growth Factor-Binding Protein 7 (IGFBP7) is an extracellular matrix (ECM) glycoprotein, highly enriched in activated vasculature during development, physiological and pathological tissue remodeling. Despite decades of research, its role in tissue (re-)vascularization is highly ambiguous, exhibiting pro- and anti-angiogenic properties in different tissue remodeling states. IGFBP7 has multiple binding partners, including structural ECM components, cytokines, chemokines, as well as several receptors. Based on current evidence, it is suggested that IGFBP7’s bioactivity is strongly dependent on the microenvironment it is embedded in. Current studies indicate that during physiological angiogenesis, IGFBP7 promotes endothelial cell attachment, luminogenesis, vessel stabilization and maturation. Its effects on other stages of angiogenesis and vessel function remain to be determined. IGFBP7 also modulates the pro-angiogenic properties of other signaling factors, such as VEGF-A and IGF, and potentially acts as a growth factor reservoir, while its actual effects on the factors’ signaling may depend on the environment IGFBP7 is embedded in. Besides (re-)vascularization, IGFBP7 clearly promotes progenitor and stem cell commitment and may exhibit anti-inflammatory and anti-fibrotic properties. Nonetheless, its role in inflammation, immunomodulation, fibrosis and cellular senescence is again likely to be context-dependent. Future studies are required to shed more light on the intricate functioning of IGFBP7.
Assessing vaginal microbiome through Vaginal Microecology Evaluation System as a predictor for in vitro fertilization outcomes: a retrospective study
Authors: Tian Quan , Jin Shengxi , Zhang Guangmin , Liu Yujie , Liu Jianxin , Tang Xiuming , Li Yufeng , Liu Jiane , Liu Yifei , Wang Zheng
Published: July 2024

Objective

This study aims to evaluate the effectiveness of the Vaginal Microecology Evaluation System (VMES) in assessing the dynamics of the vaginal microbiome (VM) throughout the process of in vitro fertilization and embryo transfer (IVF-ET). Furthermore, it seeks to explore the potential correlation between distinct types of VM ecology and the success rate of IVF-ET.

Methods

This study employed VMES to ascertain the composition of the VM. Data were collected from infertile women who underwent their initial IVF-ET treatment for tubal factor between January 2018 and December 2021. A retrospective analysis of pregnancy outcomes resulting from their fresh embryo transfer was conducted to determine the predictive significance of the vaginal microenvironment.

Results

We demonstrate that VMES is able to predict IVF-ET outcomes in patients diagnosed with Bacterial Vaginosis (BV). Notably, a discernible shift in the VM was observed in a decent subset of patients following Controlled Ovarian Stimulation (COS), though this phenomenon was not universal across all participants. Specifically, there was a noteworthy increase in the proportion of patients exhibiting BV and uncharacterized dysbiosis subsequent to COS. Furthermore, our investigation revealed a significant correlation between VM and both the live birth rate and early miscarriage rate. Employing a multivariable logistic regression model, we identified that VM status pre-COS, VM status post-COS, patient age, and the number of embryos transferred emerged as independent predictors of the live birth rate.

Conclusion

Our study suggests that, during IVF-ET treatment, the VMES can effectively detect changes in the VM, which are strongly correlated with the pregnancy outcome of IVF-ET procedures.
Neoadjuvant treatment with lenvatinib and pembrolizumab in a BRAF V600E-mutated anaplastic thyroid cancer: a case report
Authors: Barbaro Daniele , Forleo Raffaella , Profilo Maria Antonietta , Lapi Paola , Giani Carlotta , Torregrossa Liborio , Macerola Elisabetta , Materazzi Gabriele
Published: July 2024

Background

Tyrosine kinase inhibitors (TKIs) and immunotherapy have been proposed for advanced metastatic anaplastic thyroid cancer (ATC). We report a case of BRAF V600E-mutated ATC in which lenvatinib (L) plus pembrolizumab (P) enabled neoadjuvant treatment.

Case presentation

A male patient aged 65 years presented with a rapidly enlarging left latero-cervical mass. Fine needle aspiration was suggestive of ATC. Surgical consultation excluded radical surgery. While awaiting molecular profile analysis and considering the fast evolution of the disease, treatment with L and P was started. L was started at a dose of 14 mg daily, while P was started at the standard regimen (200 mg every 3 weeks). After 1 month, computerized tomography showed a reduction in the mass with almost complete colliquative degeneration, and the carotid artery wall was free from infiltration. Radical surgery was performed. Histology confirmed papillary thyroid cancer (PTC) in the left lobe and ATC with extensive necrosis in the left latero-cervical lymph node metastasis. The margins were free of tumors (R0). A BRAF V600E mutation was present in both PTC and ATC. At the 1-year follow-up, the patient was free of disease.

Conclusion

L and P in combination also appeared to be effective as a neoadjuvant treatment for BRAF V600E-mutated ATC. This combination treatment could be used when there is an opportunity for complete resection of the cancer, and as soon as possible. The intermediate dose of 14 mg of L appeared to be well tolerated and effective.
Advanced strategy of grid-forming wind storage systems for cooperative DC power support
Authors: Zhang Xiaoke , Wang Jiaqi , Gao Zan , Zhang Shaofeng , Teng Weijun
Published: July 2024

Grid-forming (GFM) wind storage systems (WSSs) possess the capability of actively building frequency and phase, enabling faster frequency response. The frequency regulation power of GFM WSSs is provided by both the rotor of wind turbine and the battery storage (BS) in parallel with DC capacitor. However, with existing control strategies, the energy storage immediately responds to both small and large grid disturbances. The frequent responses significantly decrease the lifespan of energy storage. To address this issue, a cooperative strategy between rotor and energy storage is necessary. This paper proposes an advanced strategy of GFM WSSs for cooperative DC power support. The cooperative principle is that for small disturbances, the BS is disabled and total frequency regulation power is provided by the rotor, while for large disturbances, the BS is enabled to cooperatively provide power support with the rotor. The proposed cooperative strategy can decrease the charging and discharging times of BS with a small range of rotor speed fluctuation, and then the service life of BS can be significantly extended. Simulation results validate the effectiveness and superiority of the proposed strategy.
Assessment of nitrogen and phosphorus pollution based on multi-source data and the InVEST model in the Henan section of Yellow River Basin, China
Authors: Yang Xu , Qiu Shike , Wang Chao , Du Jun , Zhang Xinli , Sun Tingting
Published: July 2024

In recent years, non-point source pollution (NPSP) has become prominent in the Yellow River Basin (YRB) of China and seriously affects human survival and sustainable development. The Henan section was selected as an example region of the YRB in China, and the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model has been used to quantitatively evaluate nitrogen (N) and phosphorus (P). The results show that (1) the cultivated land (CL), grassland (GL), and unused land (UL) decreased, while forest land (FL), water areas (WAs), and built-up areas (BAs) increased in 2000–2020, and precipitation increased from the northeast to the southwest in 2000–2020; (2) the N export was much more than P export in 2000, 2010, and 2020, and the N and P exports increased in 2000–2020; the spatial distribution of N and P export changes was different in the whole basin in 2000–2010, 2010–2020, and 2000–2020; (3) the N and P exports decreased in 2000–2010, 2010–2020, and 2000–2020 with increasing precipitation; and (4) the N and P exports on CL and BAs were more than those on the other land-use types, and the overall change trends of N and P exports on all land-use types increased from 2000 to 2020.
Genetic correlation and causal relationship between sleep and myopia: a mendelian randomization study
Authors: Zhu Guandong , Tian Ruikang , Zhou Dengke , Qin Xuejiao
Published: July 2024

Purpose

To investigate the genetic correlation and causal links between sleep traits (including sleep duration, chronotype, and insomnia) and myopia.

Methods

Summary data on three sleep traits (sleep duration, chronotype and insomnia) and myopia from FinnGen (n = 214,211) and UK Biobank (n = 460,536) were analyzed using linkage disequilibrium score regression (LD Score), univariable and multivariable mendelian randomization (MR) experiments and Causal Analysis Using Summary Effect (CAUSE) estimation.

Results

LD Score regression detected candidate genetic correlation between sleep traits and myopia, such as sleep duration, chronotype (Genetic Correlation Z-score >10.00, h2_observed_p < 0.005, Lambda GC > 1.05, p > 0.05). Univariable MR analyses indicated that increased sleep duration has a promotional effect on the occurrence of myopia (p = 0.046 < 0.05, P_FDR = 0.138 < 0.2, OR = 2.872, 95% CI: 1.018–8.101). However, after accounting for potential confounding factors, multivariable MR and CAUSE analysis did not provide evidence for a causal effect of the three sleep traits on myopia.

Conclusion

There may be a potential genetic correlation between sleep duration, chronotype and myopia. However, neither of sleep duration, chronotype or insomnia had causal effect on myopia.
The use of digital platforms by citizen aid actors during the Ukraine humanitarian crisis
Authors: Sithole Tererai Obey
Published: July 2024

Following the Ukraine humanitarian crisis, which was a result of the war in Ukraine, ordinary citizens stepped up to spontaneously coordinate various humanitarian responses to support affected populations. In this article such individuals who founded or coordinated this form of spontaneous humanitarian aid are referred to as citizen aid actors (CAA). This paper explores the work of citizen aid actors in Poland, a country which received many of the people displaced by the war in Ukraine. The study applies the concept of digital affordances to illustrate and argue that citizen aid actors relied on the features available on digital platforms to attain their goals. It is an outcome of a qualitative research approach where interviews, participant observation, and analysis of relevant online material about the studied citizen aid actors were used as methods of collecting data. The findings indicate that these actors used diverse digital platforms at different stages of the humanitarian aid projects, from establishment, organization and sustenance. While this study demonstrates how specific digital platforms contributed to the accomplishment of the work done by CAAs, it also highlights how problematic it can be when the actors largely rely on digital platforms. As such, potential risks associated with overreliance on digital platforms as a way of implementing projects are factored in. Ensuing concerns include the presence of online trolls, the spreading of fake news, and internet disruptions as potential obstacles for the success of the aid projects.
ATP-P2X7R pathway activation limits the Tfh cell compartment during pediatric RSV infection
Authors: Russo Constanza , Raiden Silvina , Algieri Silvia , Bruera María José , De Carli Norberto , Sarli Mariam , Cairoli Héctor , De Lillo Leonardo , Morales Ivanna , Seery Vanesa , Otero Adrián , Sananez Inés , Simaz Nancy , Alfiero Gisela , Rubino Gabriela , Moya Néstor , Aedo Portela Luisa , Herrero Mauro , Blanco Marina , Salcedo Pereira Misael , Ferrero Fernando , Geffner Jorge , Arruvito Lourdes
Published: July 2024

Background

Follicular helper T cells (Tfh) are pivotal in B cell responses. Activation of the purinergic receptor P2X7 on Tfh cells regulates their activity. We investigated the ATP-P2X7R axis in circulating Tfh (cTfh) cells during Respiratory Syncytial Virus (RSV) infection.

Methods

We analyzed two cohorts: children with RSV infection (moderate, n=30; severe, n=21) and healthy children (n=23). We utilized ELISA to quantify the levels of PreF RSV protein-specific IgG antibodies, IL-21 cytokine, and soluble P2X7R (sP2X7R) in both plasma and nasopharyngeal aspirates (NPA). Additionally, luminometry was employed to determine ATP levels in plasma, NPA and supernatant culture. The frequency of cTfh cells, P2X7R expression, and plasmablasts were assessed by flow cytometry. To evaluate apoptosis, proliferation, and IL-21 production by cTfh cells, we cultured PBMCs in the presence of Bz-ATP and/or P2X7R antagonist (KN-62) and a flow cytometry analysis was performed.

Results

In children with severe RSV disease, we observed diminished titers of neutralizing anti-PreF IgG antibodies. Additionally, severe infections, compared to moderate cases, were associated with fewer cTfh cells and reduced plasma levels of IL-21. Our investigation revealed dysregulation in the ATP-P2X7R pathway during RSV infection. This was characterized by elevated ATP levels in both plasma and NPA samples, increased expression of P2X7R on cTfh cells, lower levels of sP2X7R, and heightened ATP release from PBMCs upon stimulation, particularly evident in severe cases. Importantly, ATP exposure decreased cTfh proliferative response and IL-21 production, while promoting their apoptosis. The P2X7R antagonist KN-62 mitigated these effects. Furthermore, disease severity positively correlated with ATP levels in plasma and NPA samples and inversely correlated with cTfh frequency.

Conclusion

Our findings indicate that activation of the ATP-P2X7R pathway during RSV infection may contribute to limiting the cTfh cell compartment by promoting cell death and dysfunction, ultimately leading to increased disease severity.
Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitis
Authors: Ruiz-Pablos Manuel , Paiva Bruno , Zabaleta Aintzane
Published: July 2024

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), long COVID (LC) and post-COVID-19 vaccine syndrome show similarities in their pathophysiology and clinical manifestations. These disorders are related to viral or adjuvant persistence, immunological alterations, autoimmune diseases and hormonal imbalances. A developmental model is postulated that involves the interaction between immune hyperactivation, autoimmune hypophysitis or pituitary hypophysitis, and immune depletion. This process might begin with a deficient CD4 T-cell response to viral infections in genetically predisposed individuals (HLA-DRB1), followed by an uncontrolled immune response with CD8 T-cell hyperactivation and elevated antibody production, some of which may be directed against autoantigens, which can trigger autoimmune hypophysitis or direct damage to the pituitary, resulting in decreased production of pituitary hormones, such as ACTH. As the disease progresses, prolonged exposure to viral antigens can lead to exhaustion of the immune system, exacerbating symptoms and pathology. It is suggested that these disorders could be included in the autoimmune/adjuvant-induced inflammatory syndrome (ASIA) because of their similar clinical manifestations and possible relationship to genetic factors, such as polymorphisms in the HLA-DRB1 gene. In addition, it is proposed that treatment with antivirals, corticosteroids/ginseng, antioxidants, and metabolic precursors could improve symptoms by modulating the immune response, pituitary function, inflammation and oxidative stress. Therefore, the purpose of this review is to suggest a possible autoimmune origin against the adenohypophysis and a possible improvement of symptoms after treatment with corticosteroid replacement therapy.
Donor-derived cell-free DNA predicted allograft rejection and severe microvascular inflammation in kidney transplant recipients
Authors: Kim Hyung Duk , Bae Hyunjoo , Kang Hyunhye , Lee Hanbi , Eum Sang Hun , Yang Chul Woo , Choi Yeong Jin , Chung Byung Ha , Oh Eun-Jee
Published: July 2024

Introduction

The aim of this study is to investigate the clinical validity of donor-derived cell-free DNA (dd-cfDNA) in comparison with that of donor specific anti-HLA antibody (DSA) for predicting biopsy-proven rejection (BPR)and severe microvascular inflammation (severe MVI) in kidney transplant recipients (KTRs).

Methods

In this prospective observational investigation, 64 KTRs who underwent the indicated biopsies were included. Blood samples collected prior to biopsy were tested for dd-cfDNA and DSA. Biopsy specimens were classified by a renal pathologist according to the Banff classification. The predictive performance of dd-cfDNA and DSA for histological allograft diagnosis was assessed.

Results

KTRs were categorized into the high and low dd-cfDNA groups based on a level of 0.4%. Eighteen patients (28.1%) had positive DSA at biopsy, exhibiting higher dd-cfDNA levels than the DSA-negative patients. BPR and severe MVI incidences were elevated in the high dd-cfDNA group (BPR: 42.9% vs. 3.4%, P <0.001; severe MVI: 37.1% vs. 3.4%, P = 0.001). Also, elevated glomerulitis and MVI scores were observed in the high dd-cfDNA group. DSA showed the highest predictive value for BPR (AUC = 0.880), whereas dd-cfDNA alone excelled in predicting severe MVI (AUC = 0.855). Combination of DSA and dd-cfDNA (>0.4%) yielded sensitivities of 80.0% and 50.0% with specificities of 90.7% and 88.0% for antibody-mediated rejection and severe MVI detection, respectively.

Conclusion

The dd-cfDNA test is a predictive tool for BPR and severe MVI, and it can improve the performance, especially when combined with DSA for BPR.
Impact of ocean in-situ observations on ECMWF sub-seasonal forecasts
Authors: Balan-Sarojini Beena , Balmaseda Magdalena Alonso , Vitart Frédéric , Roberts Christopher David , Zuo Hao , Tietsche Steffen , Mayer Michael
Published: July 2024

We assess for the first time the impact of in-situ ocean observations on European Centre for Medium-Range Weather Forecasts (ECMWF) sub-seasonal forecasts of both ocean and atmospheric conditions. A series of coupled reforecasts have been conducted for the period 1993-2015, in which different sets of ocean observations were withdrawn in the production of the ocean initial conditions. Removal of all ocean in-situ observations in the initial conditions leads to significant degradation in the forecasts of ocean surface and subsurface mean state at lead times from week 1 to week 4. The negative impact is predominantly caused by the removal of the Argo observing system in recent decades. Changes in the mean state of atmospheric variables are comparatively small but significant in the forecasts of lower and upper atmospheric circulation over large regions. Our results highlight the value of continuous, real-time in-situ observations of the surface and subsurface ocean for coupled forecasts in the sub-seasonal range.
Influence of preparation parameters on rheological properties and relation analysis of waste rubber modified bitumen mastic
Authors: Zhang Honggang , Zhang Yangpeng , Chen Jie , Liu Wenchang , Wang Wensheng
Published: July 2024

Waste rubber modified bitumen has gained significant attention as a sustainable and innovative material in the field of pavement engineering. This study aims to evaluate the performance of rubber modified bitumen mastic by considering its rheological properties, specifically focusing on preparation parameters, i.e., rubber content, mesh number, and filler to bitumen ratio. From the experimental results, the rheological properties of rubber modified bitumen mastic were significantly influenced by preparation parameters. Increasing the rubber powder content in bitumen mastic results in higher viscosity. Increasing the rubber content improves high-temperature rutting resistance to a certain extent, however, excessive rubber powder content would result in weakened high-temperature performance improvement. The rutting factor decreases gradually with an increase in the rubber mesh number. A ratio of filler to bitumen of 0.95 exhibits the best resistance to rutting at high temperatures. Higher rubber content and larger mesh number correspond to stronger low-temperature crack resistance in bitumen mastic. As the ratio of filler to bitumen increases, the low-temperature deformation capacity gradually decreases, resulting in weaker low-temperature crack resistance. Based on the grey relation analysis, the ratio of filler to bitumen has the greatest impact on the high and low-temperature rheological properties of bitumen mastic, followed by the rubber content. The rubber mesh number has a relatively lower impact. It is crucial to control the ratio of filler to bitumen to avoid excessive values. When possible, a higher rubber powder content should be used while meeting process requirements. These findings provide valuable insights into the design and optimization of rubber modified bitumen mastic, which can contribute to the development of sustainable and high-performance bitumen mixtures, promoting the use of recycled rubber in pavement engineering.
Evaluating Chatbot responses to patient questions in the field of glaucoma
Authors: Tan Darren Ngiap Hao , Tham Yih-Chung , Koh Victor , Loon Seng Chee , Aquino Maria Cecilia , Lun Katherine , Cheng Ching-Yu , Ngiam Kee Yuan , Tan Marcus
Published: July 2024

Objective

The aim of this study was to evaluate the accuracy, comprehensiveness, and safety of a publicly available large language model (LLM)—ChatGPT in the sub-domain of glaucoma.

Design

Evaluation of diagnostic test or technology.

Subjects, participants, and/or controls

We seek to evaluate the responses of an artificial intelligence chatbot ChatGPT (version GPT-3.5, OpenAI).

Methods, intervention, or testing

We curated 24 clinically relevant questions in the domain of glaucoma. The questions spanned four categories: pertaining to diagnosis, treatment, surgeries, and ocular emergencies. Each question was posed to the LLM and the responses obtained were graded by an expert grader panel of three glaucoma specialists with combined experience of more than 30 years in the field. For responses which performed poorly, the LLM was further prompted to self-correct. The subsequent responses were then re-evaluated by the expert panel.

Main outcome measures

Accuracy, comprehensiveness, and safety of the responses of a public domain LLM.

Results

There were a total of 24 questions and three expert graders with a total number of responses of n = 72. The scores were ranked from 1 to 4, where 4 represents the best score with a complete and accurate response. The mean score of the expert panel was 3.29 with a standard deviation of 0.484. Out of the 24 question-response pairs, seven (29.2%) of them had a mean inter-grader score of 3 or less. The mean score of the original seven question-response pairs was 2.96 which rose to 3.58 after an opportunity to self-correct (z-score − 3.27, p = 0.001, Mann–Whitney U). The seven out of 24 question-response pairs which performed poorly were given a chance to self-correct. After self-correction, the proportion of responses obtaining a full score increased from 22/72 (30.6%) to 12/21 (57.1%), (p = 0.026, χ2 test).

Conclusion

LLMs show great promise in the realm of glaucoma with additional capabilities of self-correction. The application of LLMs in glaucoma is still in its infancy, and still requires further research and validation.
Capturing Legionella pneumophila effector enzymes using a ubiquitin derived photo-activatable probe
Authors: Kloet Max S. , van der Heden van Noort Gerbrand J.
Published: July 2024

Upon infection of host cells the Legionella pneumophila bacterium releases a multitude of effector enzymes into the host’s cytoplasm that manipulate cellular host pathways, including the host-ubiquitination pathways. The effectors belonging to the SidE-family are involved in non-canonical phosphoribosyl serine ubiquitination (PR-ubiquitination) of host substrate proteins. This results in the recruitment of ER-remodeling proteins and the formation of a Legionella-containing vacuole which is crucial in the onset of legionnaires disease. PR-ubiquitination is a dynamic process reversed by other Legionella effectors called Dups. During PR-Ubiquitin phosphodiester hydrolysis Dups form a covalent intermediate with the phosphoribosyl ubiquitylated protein using its active site His67 residue. We envisioned that covalent probes to target Legionella effectors could be of value to study these effectors and contribute to deciphering the complex biology of Legionella infection. Hence we effectively installed a photo-activatable pyridinium warhead on the 5′-OH of triazole-linked ribosylated ubiquitin allowing crosslinking of the probe to the catalytic histidine residues in Legionella SidE or Dup enzymes. In vitro tests on recombinantly expressed DupA and SdeAPDE revealed that the probe was able to capture the enzymes covalently upon photo-activation.
Limitations of human brain organoids to study neurodegenerative diseases: a manual to survive
Authors: Urrestizala-Arenaza Nerea , Cerchio Sonia , Cavaliere Fabio , Magliaro Chiara
Published: July 2024

In 2013, M. Lancaster described the first protocol to obtain human brain organoids. These organoids, usually generated from human-induced pluripotent stem cells, can mimic the three-dimensional structure of the human brain. While they recapitulate the salient developmental stages of the human brain, their use to investigate the onset and mechanisms of neurodegenerative diseases still faces crucial limitations. In this review, we aim to highlight these limitations, which hinder brain organoids from becoming reliable models to study neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Specifically, we will describe structural and biological impediments, including the lack of an aging footprint, angiogenesis, myelination, and the inclusion of functional and immunocompetent microglia—all important factors in the onset of neurodegeneration in AD, PD, and ALS. Additionally, we will discuss technical limitations for monitoring the microanatomy and electrophysiology of these organoids. In parallel, we will propose solutions to overcome the current limitations, thereby making human brain organoids a more reliable tool to model neurodegeneration.
Vagus nerve stimulation for the therapy of Dravet syndrome: a systematic review and meta-analysis
Authors: Chen Shuang , Li Man , Huang Ming
Published: July 2024

Objective

Dravet syndrome (DS) is a refractory developmental and epileptic encephalopathy characterized by seizures, developmental delay and cognitive impairment with a variety of comorbidities, including autism-like behavior, speech dysfunction, and ataxia. Vagus nerve stimulation (VNS) is one of the common therapies for DS. Here, we aim to perform a meta-analysis and systematic review of the efficacy of VNS in DS patients.

Methods

We systematically searched four databases (PubMed, Embase, Cochrane and CNKI) to identify potentially eligible studies from their inception to January 2024. These studies provided the effective rate of VNS in treating patients with DS. The proportions of DS patients achieving ≥50% reduction of seizure frequency were extracted from these studies. Meta-analyses were performed to respectively evaluate the efficacy of VNS for DS after 3, 6, 12, 18, 24 and 36 months.

Results

Sixteen trials with a total of 173 patients were included. Meta-analyses showed that the pooled efficiency was 0.54 (95% CI 0.43–0.65) in the DS patients treated with VNS (p < 0.05). Meanwhile, the pooled efficiency respectively was 0.42 (95% CI 0.25–0.61), 0.54 (95% CI 0.39–0.69), 0.51 (95% CI 0.39–0.66), and 0.49 (95% CI 0.36–0.63) in the DS patients treated with VNS after 3, 6, 12 and 24 months (p < 0.05).

Conclusion

This study suggests that VNS is effective in the treatment of DS. However, few studies have focused on VNS for DS, and there is a lack of high-quality evidence. Thus, high-quality randomized controlled trials are needed to confirm the efficacy of VNS in DS.
What if Hitler had won WWII and met Kennedy in 1964? Perception and evaluation of counterfactual historical fiction
Authors: Kakimova Ainur , Salgaro Massimo
Published: July 2024

Introduction

This study investigates the cognitive processing and perception of counterfactual historical fiction and its effects on readers' receptivity to fascism, superstitious beliefs, and satisfaction with the present state of politics. Counterfactual historical fiction presents alternative realities where history diverges from the official historiography, such as in Robert Harris' novel Fatherland, which depicts a counterfactual world where Hitler won WWII. It was hypothesized that reading this genre incurs additional cognitive costs and is perceived with less realism and more aesthetic appreciation compared to historical fiction.

Methods

Seventy-four subjects were divided into two groups and presented with two versions of paragraphs from Fatherland. An experimental group read the original version, describing a counterfactual reality where Hitler is still alive in 1964 (counterfactual historical fiction). A control group read a manipulated version, where events are made plausible by being backdated to 1941 (historical fiction). The study employed a triangulation of methods, utilizing online eye tracking and self-report questionnaires with 7-point Likert scale measurements.

Results

The results indicate that counterfactual historical fiction is associated with increased cognitive demands at the first point of divergence, i.e., the first linguistic cue indicating counterfactuality. This genre also induced less perceived realism of history (factuality) and more surprise. Both versions of the text impacted readers by decreasing agreement with fascism, reducing superstitious beliefs, and enhancing their positive evaluation of the current political situation.

Discussion

The study reveals the cognitive processing of counterfactual historical fiction, highlighting the need for revising current theoretical assumptions. Additionally, the positive impact on readers' attitudes and beliefs may underscore literature's potential role in fostering critical thinking, pro-social behavior, and satisfaction. Further research is suggested for subsequent empirical validation.
Evolutionary transfer optimization-based approach for automated ictal pattern recognition using brain signals
Authors: Swami Piyush , Maheshwari Jyoti , Kumar Mohit , Bhatia Manvir
Published: July 2024

The visual scrutinization process for detecting epileptic seizures (ictal patterns) is time-consuming and prone to manual errors, which can have serious consequences, including drug abuse and life-threatening situations. To address these challenges, expert systems for automated detection of ictal patterns have been developed, yet feature engineering remains problematic due to variability within and between subjects. Single-objective optimization approaches yield less reliable results. This study proposes a novel expert system using the non-dominated sorting genetic algorithm (NSGA)-II to detect ictal patterns in brain signals. Employing an evolutionary multi-objective optimization (EMO) approach, the classifier minimizes both the number of features and the error rate simultaneously. Input features include statistical features derived from phase space transformations, singular values, and energy values of time–frequency domain wavelet packet transform coefficients. Through evolutionary transfer optimization (ETO), the optimal feature set is determined from training datasets and passed through a generalized regression neural network (GRNN) model for pattern detection of testing datasets. The results demonstrate high accuracy with minimal computation time (<0.5 s), and EMO reduces the feature set matrix by more than half, suggesting reliability for clinical applications. In conclusion, the proposed model offers promising advancements in automating ictal pattern recognition in EEG data, with potential implications for improving epilepsy diagnosis and treatment. Further research is warranted to validate its performance across diverse datasets and investigate potential limitations.
Research progress on antitumor effects of sea buckthorn, a traditional Chinese medicine homologous to food and medicine
Authors: Xu Duojie , Yuan Ling , Meng Fandi , Lu Doudou , Che Mengying , Yang Yating , Liu Wenjing , Nan Yi
Published: July 2024

Sea buckthorn (Hippophae Fructus), as a homologous species of medicine and food, is widely used by Mongolians and Tibetans for its anti-tumor, antioxidant and liver-protecting properties. In this review, the excellent anti-tumor effect of sea buckthorn was first found through network pharmacology, and its active components such as isorhamnetin, quercetin, gallic acid and protocatechuic acid were found to have significant anti-tumor effects. The research progress and application prospect of sea buckthorn and its active components in anti-tumor types, mechanism of action, liver protection, anti-radiation and toxicology were reviewed, providing theoretical basis for the development of sea buckthorn products in the field of anti-tumor research and clinical application.