bluuebunny/crossref_metadata_2025 huggingface dataset:
DIALEKTIKA INTERNAL MASYARAKAT MERIGI SAKTI KABUPATEN BENGKULU TENGAH DALAM KONFLIK PERTAMBANGAN BATU BARA
Authors: Muzni Nurlianti , Putri Prahastiwi
Published: February 2023

Konflik lingkungan yang terjadi antara masyarakat Merigi Sakti dengan PT. Citra Buana Seraya (PT.CBS) Kabupaten Bengkulu Tengah tidak hanya menyisahkan pertentangan diantara keduanya. Kontradiktif antara perempuan dan laki-laki atau dalam konsep dialektika disebut dialektika internal, melihat bagaimana perempuan menghadapi harapan yang tidak jelas atau terjadi suatu pertentangan.Dialektika internal pada konflik pertambangan batubara ini terbagi menjadi tiga bagian. Yaitu; Keterhubungan gerakan penolakan antara perempuan dan laki-laki di Merigi Sakti (connection-autonomy), Keterlibatan perempuan dalam konflik yang Mengalami Ketidakpastian (certainty-uncertainty), dan Keterbukaan dari perempuan dan laki-laki Merigi Sakti dalam merespon konflik (opennes-closednes).Tulisan ini, merupakan bagian dari penelitian yang dilakukan pada masyarakat Merigi Sakti Kabupaten Bengkulu Tengah. Dengan mengacu pada konsep dialektis dialogis yang dikemukakan oleh Baxter and Montgomery, tulisan ini melihat melihat berbagai pertentangan di internal masyarakat selama konflik terjadi. Kata Kunci: Konflik Lingkungan, Dialektika internal, perempuan
PELUANG DAN TANTANGAN DALAM MEMETAKAN OPINI PUBLIK DI MEDIA SOSIAL
Authors: Firmansyah Mas Agus , Supriyadi Dedi
Published: February 2023

Tujuan dari tulisan ini adalah upaya untuk mengidentifkasi dan mengkaji berbagai peluang dan tantangan yang dihadapi dalam memetakan opini publik di media sosial. Berdasarkan tujuannya itulah, maka pendekatan yang digunakan untuk mendekati permasalahan dalam tulisan ini bersifat eksploratif, dengan menggunakan deskripsi analitis dalam pembahasan datanya. Melalui penelusuran dan pengalian berbagai data yang dielaborasi dari berbagai sumber,maka terdapat beberapa hal yang dapat diidentifikasi sebagai peluang maupun tantangan yang akan dihadapi ketika menjadikan media sosial sebagai basis untuk memetakan opini publik. Permasalahan lain yang sekaligus menjadi tantangan, adalah terkait dengan ketersediaan metode yang benar-benar tepat dan sesuai untuk dapat memetakan / menjaring opini publik di media sosial.

Kata Kunci: Opini Publik, Media Sosial, Teknologi Informasi dan Komunikasi (TIK)
REPRESENTASI IDENTITAS GAY DALAM KOMIK DIGITAL
Authors: Ukima Sultan Kharis , Hadiprashada Dhanurseto
Published: February 2023

Penelitian ini menggunakan metode deskriptif kualitatif dengan analisis wacana model Charles Sanders Peirce, yang menganalisis dari struktur Tanda, Objek dan Representatif sehingga dengan menggunakan analisis tersebut peneliti dapat mencapai tujuan penelitian yaitu untuk mendeskripsikan bagaimana gay digambarkan dalam Line Webtoon si Daily Life Of A Gay Couple Berdasarkan hasil analisis, kesimpulan dari Representasi identitas gay di dalamnya meliputi: (1) Representasi identitas yang dikembangkan dalam Line Webtoon Daily Life Of A Gay Couple selalu menggambarkan tanda serta konteks realitas sosial yang biasanya terjadi di kalangan masyarakat gay (2) Penggambaran gay sebagai sosok yang tertarik terhadap laki-laki yang kekar (3) Penggambaran gay sebagai orang yang pemalu (4) Penggambaran gay sebagai seseorang yang keras kepala (5) Pengakuan terhadap diri sendiri (6) Komik ini juga menggambarkan bahwa isu gay dalam masyarakat sebenarnya sangatlah luas terjadi.Kata Kunci : Representasi, Identitas Gay, Analisis Pesan, Semiotik Charles Sander Pierce
ANALISIS PENERAPAN BRAND JOURNALISM PADA WEBSITE PERUSAHAAN UNILEVER
Authors: Nurfadullah Luthfi , Widiastuti Wahyu , Sari Eka Vuspa
Published: February 2023

Brand journalism merupakan cara berkomunikasi yang kontemporer untuk sebuah Brand. Perusahaan Unilever menggunakan brand journalism untuk menjadi penerbit brand nya sendiri karna pada Website Unilever itu sendiri memiliki banyak cerita untuk diceritakan dan cerita itu bisa menjadi alat untuk menjalin hubungan akrab dengan pelanggan. Pada brand journalism harus bisa menguasai dan mengerti media online agar dapat berinteraksi dengan mudah kepada publik, dengan cara membuat konten, menggunakan fotografi, serta skllis sesuai dengan materi jurnalistik dan mendistibusikan brand journalism dengan audiens nya. Pada perusahaan Unilever tidak menggunakan konten untuk menjual tetapi konten yang dimunculkan lebih banyak mengandung informasi. Tujuan dari skripsi ini adalah Untuk mengetahui penerapan brand journalism pada Website perusahaan Unilever. Pada penelitian ini menggunakan penelitian kualitatif deskriptif. Teknik pengumpulan data yang digunakan penelitian ini adalah teknik dokumentasi. Hasil yang diperoleh menunjukkan bahwa Pada konten perusahaanunilever terdapat cerita perusahaan dan nilai nilai jurnalism, pada cerita perusahaan khususnya pada artikel mengandung brand journalism yang terdapat beberapa unsur yaitu unsur yang menarik, unsur kreatif yang sesuai dengan skenario, unsur storytelling, dan unsur softselling dan Nilai nilai jurnalisme yang mengandung pada artikel yang di analisis berupa kebaruan (newness), akibat (Impact), aktual (timeliness), kedekatan (proximity), information (information), konflik (conflict), dan keterkaitan manusiawi (human inters).

Kata Kunci: brand journalism, Website perusahaan, konten, perusahaan Unilever.
PENGARUH PROMOSI PARIWISATA TERHADAP PREFERENSI WISATAWAN MANCANEGARA DI KOTA BENGKULU
Authors: Indasari Fera , Yanto
Published: February 2023

Membentuk preferensi wisatawan dalam memilih Kota Bengkulu sebagai lokasi destinasi yang wajib dikunjungi merupakan sebuah hal yang harus dilakukan mengingat bahwa adanya visi dari yang dibuat oleh pemerintahan Kota Bengkulu adalah "Visit Wonderful Bengkulu 2020". Peningkatan jumlah wisatawan asing semakin meningkat, tetapi jumlah tersebut masih sangat jauh tertinggal daripada daerah-daerah yang lebih dulu dikenal dengan sangat baik oleh tourist mancanegara, ini karena promosi masih belum effective dilakukan Penelitian ini berjudul Pengaruh Promosi Pariwisata terhadap preferensi wisatawan mancanegara di Kota Bengkulu, tujuan dari penelitian untuk mengetahui pengaruh promosi pariwisata terhadap preferensi wisatawan mancanegara di Kota Bengkulu. Untuk mencapai tujuan visit Bengkulu maka pemerintah sudah selayaknya memberikan perhatian yang lebih untuk menjalankan promosi pariwisata mengingat promosi akan sangat membantu calon wisatawan untuk mengetahui bagaimana keadaan tujuan wisatanya.Kata Kunci : Promosi, pariwisata, visit, Bengkulu, pemandangan.
Uso de marlo de maíz como generador de porosidad controlada en cerámicos
Authors: Quaranta Nancy Esther , Varoli Romina , Caligaris Marta , Cristóbal Adrián
Published: February 2023

El objetivo de este trabajo es analizar la utilización de marlos de maíz, como material formador de poros en la fabricación de materiales cerámicos alivianados. Las materias primas, marlo molido y arcilla, fueron exhaustivamente caracterizadas. Los productos cerámicos estudiados se fabricaron a partir de arcilla comercial con el agregado de 5%, 10% y 15% en volumen de marlos, y una muestra sin biomasa adicionada a modo de referencia. Todas las mezclas con 8% de humedad se conformaron a 25MPa. Posteriormente se cocinaron a 950°C durante 3 horas. Los resultados obtenidos reflejan una alta factibilidad de utilización de esta biomasa para el uso estudiado. Los ladrillos cerámicos obtenidos poseen buenas características generales, con propiedades mecánicas que cumplen con los requerimientos del mercado. Además, se observó que la porosidad obtenida se relaciona con el tamaño y forma de las partículas de la biomasa utilizada, así como con la proporción agregada.
Of pigs and peptides
Authors:   , van Harten Roeland Maarten
Published: February 2023

There are almost one billion pigs worldwide, which are threatened by pathogenic bacteria. One of those is Streptococcus suis. There is no effective vaccine against this bacterium, leading to many diseased pigs each year, which in turn poses risks to humans. Treatment with antibiotics is possible, but in pigs the infection must be diagnosed in time, and treatment could lead to antibiotic resistance development. One solution for S. suis infections could be the host defence peptides (HDPs). HDPs are antimicrobial without inducing resistance and have immune modulatory functions which make them suitable as vaccine components. However, there is a lack of specific knowledge of HDP activity in porcine cell systems, and particularly in the context of an S. suis infection.
The HDP CATH-2 is effective in inhibiting the immune response of porcine macrophages. This could be important in, for example, effective vaccines that have sizable side effects.
S. suis has a remarkable resilience to HDPs originating in pigs, but much less against CATH-2. More research is needed to clarify the mechanism of resilience.
CATH-2 effectively inhibits porcine dendritic cell activation by both E. coli and S. suis. This could mean that CATH-2 could potentially lower side effects of a vaccine, without damaging the capacity to process the antigen (and thereby the vaccine effectivity).
CATH-2 and some derivatives have the potential to protect mice against S. suis induced disease symptoms. These CATH-2 derivatives could be used prophylactically, although this has not yet been tested in pigs.
Analiza materiałów zabytkowych / Analysis of the grave materials
Authors: Michnik Monika , Dzięgielewski Karol
Published: February 2023

The most common form of furnishing in the inhumation graves was pottery, which was found in 289 features. Vessels were deposited in two sets. One was placed next to the burial, customarily in the northern part behind the head of the deceased, less frequently in other parts of the grave. The other set of vessels was placed at the level of the pit ceiling, among the stones of the pavement or between its successive layers. The sets differ in both number and the choice of ceramic forms. The vessels by the burial are the classic ‘Upper Silesian set’, consisting of a pot, a bowl and a scoop, and there was often more than one such set. The sets placed higher in the pit are dominated by large vase-shaped vessels, plates, and the classic pot, bowl and scoop sets. Inhumation graves from the Świbie cemetery are marked by a significant saturation in metal artefacts, made of bronze (215 graves), iron (166 graves) and, less frequently, lead (seven graves). In this respect, Świbie is unique among the other necropolises of the Upper Silesia-Lesser Poland group. The assortment of metal objects includes ornaments and dress items, as well as tools and weapons. The raw material criterion must have also played a role in their selection as grave gifts, as ornaments were made of both bronze and iron (especially in the younger phase), while tools were exclusively made of iron. The deceased were buried in full ceremonial dress, and the sets of ornaments and parts of the dress preserved at inhumation burials enable its reconstruction. One distinctive element, even a hallmark of the Upper Silesia-Lesser Poland group, is the head ornaments, often of elaborate forms. Remnants of headbands (plaited or textile) were identified in the cemetery, to which spirals (called temple rings) were attached on the side, or additionally rows of bronze buttons were sewn on. The buttons were placed above the forehead (half-diadems) or all around (diadems). Other small bronze appliqués (salta leone beads or glass and amber beads) were sometimes also attached to the headbands. Diadems/bands made with lead elements, uncovered in six graves, are rare finds. Necklaces made usually of bronze, less often of iron, and necklaces of glass and glassy faience beads were strung around the neck. On the chest, the deceased had bronze and iron pins with differently shaped heads (which may have fastened the robe or adorned it). Bracelets were placed around the wrists, and ankle-rings around the ankles. The deceased were buried with tools: iron knives, sickles, axes (flat or socketed) and stone battle axes, and occasionally also items of weaponry, such as iron spearheads or bronze arrowheads.
Phospholipid composition of human myocardium in children with normoxemic and hypoxemic congenital heart diseases
Authors: Hamplová B , Pelouch V , Nováková O , Škovránková J , Hučín B , Novák F
Published: February 2023

Samples of myocardial tissue were obtained during cardiac surgery from children operated for different types of normoxemic and hypoxemic congenital heart diseases. The phospholipid composition was analyzed by thin layer chromatography. The concentration of total phospholipids (PL), phosphatidylcholine and phosphatidylethanolamine (PE) was found lower in atrial tissue of both normoxemic and hypoxemic groups in comparison with the ventricles. When comparing the difference between hypoxemic and normoxemic defects, hypoxemia was found to increase the concentration of total PL, PE and phosphatidylserine in ventricles and total PL and PE in the atria. The increased level of particular phospholipid species may represent adaptive mechanisms to hypoxemia in children with congenital heart diseases.
Clozapine blocks sympathetic and thermogenic reactions induced by orexin A in rat
Authors: Monda M , Viggiano An , Viggiano Al , Fuccio F , De Luca V
Published: February 2023

This experiment tested the effect of clozapine on the sympathetic and thermogenic effects induced by orexin A. The firing rates of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures were monitored in urethane-anesthetized male Sprague-Dawley rats before and for 5 h after an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle. The same procedure was carried out in rats treated with orexin A plus an intraperitoneal administration of clozapine (8 mg/kg bw), an atypical antipsychotic that is largely used in the therapy of schizophrenia. The same variables were monitored in rats with clozapine alone. A group of rats with saline injection served as control. The results show that orexin A increases the sympathetic firing rate, IBAT and colonic temperatures. Clozapine blocks completely the reactions due to orexin A. These findings suggest that clozapine influences strongly the thermogenic role of orexin A. Furthermore, the remarkable hyperthermic role played by orexin A is confirmed.
The A-204C polymorphism in the cholesterol 7α-hydroxylase (CYP7A1) gene determines the cholesterolemia responsiveness to a high-fat diet
Authors: Kovář J , Hubáček JA , Suchánek P , Poledne R
Published: February 2023

The aim of the study was to ascertain whether the A-204C polymorphism in the cholesterol 7-hydroxylase (CYP7A1) gene plays any role in determining LDL-cholesterol (LDL-C) concentration responsiveness to a high-fat diet. The concentrations of total cholesterol and LDL-cholesterol were measured in eleven healthy men (age: 30.9±3.2 years; BMI: 24.9±2.7 kg/m2) who were homozygous for either the -204A or -204C allele, after 3 weeks on a low-fat (LF) diet and 3 weeks on a high-fat (HF) diet. During both dietary regimens, the isocaloric amount of food was provided to volunteers; LF diet contained 22 % of energy as a fat and 2.2 mg of cholesterol/kg of body weight a day, HF diet 40 % of fat and 9.7 mg of cholesterol/kg of body weight a day. In six subjects homozygous for the -204C allele, the concentrations of cholesterol and LDL-cholesterol were significantly higher on HF than on LF diet (cholesterol: 4.62 vs. 4.00 mmol/l, p<0.05; LDL-C: 2.15 vs. 1.63 mmol/l, p<0.01, respectively); no significant change was observed in five subjects homozygous for the -204A allele. There were no other differences in lipid and lipoprotein-lipid concentrations. Therefore, the polymorphism in the cholesterol 7α-hydroxylase promotor region seems to be involved in the determination of cholesterol and LDL-C responsiveness to a dietary fat challenge.
A Peek at Prehistoric Paisley: Early Bronze Age Evidence from Wellmeadow Street
Authors: Lowther Jessica
Published: February 2023

Minor archaeological works completed at Wellmeadow Street, Paisley between 2017 and 2018 have identified evidence of prehistoric activity in the centre of the city. Comprising a single prehistoric feature and a shafthole stone, the finds from these works demonstrate the importance of archaeological mitigation, even in areas of low expectation.
A Medieval Rural Domestic Structure at Quien, Isle of Bute
Authors: Duffy Paul R. J.
Published: February 2023

Archaeological investigations were undertaken at Quien, Isle of Bute in 2010 as part of the Discover Bute Landscape Partnership Scheme. Excavations demonstrated that a putative early medieval chapel in fact dates to between the 11thand 13thcenturies AD. Associated artefacts from the surrounding enclosure bank suggest a more domestic character to the structure. An isolated pit also provided evidence of prehistoric activity in the vicinity.
Pendampingan Pemutakhiran Data Kependudukan pada E-Office Desa sebagai Upaya Mewujudkan Tertib Administrasi Kependudukan di Desa Cibeusi Kecamatan Jatinangor, Sumedang, Jawa Barat
Authors: Hartati Sri
Published: February 2023

Kegiatan pengabdian kepada masyarakat pendampingan pemutakhiran data kepedudukan pada aplikasi e-Office desa  bertujuan meningkatkan pemahaman dan skill  petugas pengolah data di RT/RW dan  e-Office desa (Enumerator) dalam melaksanakan pemutakhiran data kependudukan sebagai upaya mewujudkan tertib administrasi kependudukan. Metode yang digunakan dalam kegiatan pengabdian masyarakat ini yakni sosialisasi, pelatihan dan pendampingan  input data. Pengumpulan data menggunakan: wawancara,observasi dan dokumentasi. Kegiatan pengabdian kepada masyarakat ini dilakukan  dalam tiga tahap yakni: pra survey, pelaksanaan program berupa: sosialisasi, pelatihan dan pendampingan dan evaluasi. Sosialisasi,   dilakukan dengan memberikan materi antara lain:  defenisi administrasi kependudukan, jenis-jenis administrasi kependudukan, pentingnya administrasi kependudukan,  tertib admnistrasi kependudukan, sistem informasi kependudukan, aplikasi e-office desa dan SAKIP Desa. Pelatihan dan pendampingan input data, diperuntukan bagi  petugas di RT/RW dan  penginput data pada e-Office Desa (Enumerator). Kegiatan dilaksanakan selama empat hari dengan jumlah peserta sebanyak 20 orang. Hasil kegiatan pendampingan pemutakhiran data kependudukan, diperoleh sebanyak 1.795 KK ( 89%) dan  5.693 jiwa  (94,25%) telah dilakukan pendataan oleh petugas RT/RW, sisanya sebanyak 219 KK (11%) dan 347 Jiwa (5,75%) belum terdata karena berbagai kendala lapangan, khususnya di RW 07 dan RW 11.  Sementara capaian perekaman data pada e-Office Desa  yakni: SDGs   288 KK (14,29%) ,1.306 jiwa (21,62%) dan Desa Cantik  mencapai 71,25%.
Optimasi Pengelolaan Marketplace Usaha Rumahan di Imogiri
Authors: Hidayati Ulfah , Wisataone Voettie
Published: February 2023

Tujuan dari kegiatan pengabdian kepada Masyarakat (PkM) ini adalah untuk mengoptimalkan skill pengelolaan marketplace bagi para pelaku usaha rumahan. Maksud pengusaha rumahan di sini adalah ibu rumah tangga yang tergabung dalam kelompok PKK kelurahan Imogiri, Bantul, dan memiliki usaha yang dijalankan dari rumah. Pada tahun 2021, Tim PkM UNY yang terdiri dari dosen dan mahasiswa sudah melakukan pelatihan untuk pembuatan marketplace shopee dan fotografi produk. Selanjutnya, pada tahun 2022 Tim PkM melakukan pelatihan lanjutan dengan tema optimasi pengelolaan marketplace. Dalam pelatihan tersebut dilakukan pendampingan pra acara dan pasca acara selain dua materi utama yang disampaikan. Pelatihan dihadiri oleh 30 peserta yang merupakan anggota PKK Kelurahan Imogiri. Sebelum acara, Tim PkM melakukan pendampingan untuk pembuatan logo produk bagi pelaku usaha yang belum memiliki logo. Dalam pendampingan tersebut beberapa pelaku usaha berhasil membuat logo produk jualannya. Selanjutnya pada materi utama disampaikan topik mengenai optimasi pengelolaan marketplace melalui SEO (Search Engine Optimization) dan kiat dalam membangun brand toko online. Setelah penyampaian materi utama, Tim PkM melakukan pendampingan kepada peserta untuk membuat keyword guna mengoptimasi SEO. Beberapa peserta berhasil mendapatkan banyak keyword baru dan beberapa yang lainnya hanya sedikit mendapatkan keyword untuk produk onlinenya karena keterbatasan waktu pelatihan. Dalam pelatihan ini Tim PkM UNY memberikan angket untuk mengukur kepahaman peserta dan respon peserta untuk acara pelatihan tersebut. Dari angket tersebut nampak bahwa pengetahuan peserta meningkat dan juga peserta memberikan respon yang positif terhadap pelatihan yang diberikan.
Perancangan Media Pembelajaran Bahasa Mandarin Tingkat HSK 1 Berbasis Video
Authors: Carlie Jhon , Deli Deli
Published: February 2023

Pada zaman sekarang, Bahasa sudah tidak terlepas dari kehidupan manusia, karena manusia merupakan makhluk sosial. Bahasa memiliki peranan yang sangat penting di dunia. Dengan adanya bahasa, manusia dapat mengungkapkan perasaan, gagasan ataupun ide kepada orang lain. Salah satu bahasa internasional yang telah diakui oleh banyak negara ialah Bahasa Mandarin. Bahasa ini memiliki karakteristik yang unik dengan huruf dan penulisan yang berbeda dengan bahasa lain. Bahasa Mandarin juga memiliki intonasi nada pada setiap katanya. Peneliti melakukan perancangan media pembelajaran Bahasa Mandarin tingkat HSK 1 berbasis video dengan menggunakan metode RND (Research and Development) yang mengarah pada model ADDIE (Analisis, Desain, Pengembangan, Implementasi, Evaluasi). Model ADDIE sering digunakan dalam perancangan media pembelajaran, karena ADDIE merupakan model kerangka kerja simpel yang berguna dalam merancang media pembelajaran, dimana prosesnya dapat terlaksanakan dalam berbagai pengaturan karena strukturnya umum. Bahasa mandarin juga telah diakui oleh dunia bahwa bahasa ini merupakan salah satu bahasa yang sulit untuk dipelajari. Rancangan video pembelajaran ini dibuat berdasarkan materi yang diberikan oleh ahli materi serta pencarian sumber di situs website. Luaran dari proyek ini adalah sebuah video dengan 4 jenis topik pembelajaran bahasa mandarin tingkat HSK 1. Perancangan video pembelajaran ini diharapkan dapat membantu para pelajar dan para penutur bahasa dalam memahami materi serta pengambilan ujian HSK 1.
Plitidepsin in adult patients with COVID-19 requiring hospital admission: A long-term follow-up analysis
Authors: Varona Jose F. , Landete Pedro , Paredes Roger , Vates Roberto , Torralba Miguel , Guisado-Vasco Pablo , Porras Lourdes , Muñoz Patricia , Gijon Paloma , Ancochea Julio , Saiz Elena , Meira Fernanda , Jimeno Jose M. , Lopez-Martin Jose A. , Estrada Vicente
Published: February 2023

Introduction

The APLICOV-PC study assessed the safety and preliminary efficacy of plitidepsin in hospitalized adult patients with COVID-19. In this follow-up study (E-APLICOV), the incidence of post-COVID-19 morbidity was evaluated and any long-term complications were characterized.

Methods

Between January 18 and March 16, 2022, 34 of the 45 adult patients who received therapy with plitidepsin in the APLICOV-PC study were enrolled in E-APLICOV (median time from plitidepsin first dose to E-APLICOV enrollment, 16.8 months [range, 15.2–19.5 months]). All patients were functionally autonomous with regard to daily living (Barthel index: 100) and had normal physical examinations.

Results

From the APLICOV-PC date of discharge to the date of the extension visit, neither Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5) grade 3-4 complications nor QT prolongation or significant electrocardiogram (EKG) abnormalities were reported. Five (14.7%) patients had another COVID-19 episode after initial discharge from APLICOV-PC, and in 2 patients (5.9%), previously unreported chest X-ray findings were documented. Spirometry and lung-diffusion tests were normal in 29 (85.3%) and 27 (79.4%) patients, respectively, and 3 patients needed additional oxygen supplementation after initial hospital discharge. None of these patients required subsequent hospital readmission for disease-related complications.

Discussion

In conclusion, plitidepsin has demonstrated a favorable long-term safety profile in adult patients hospitalized for COVID-19. With the constraints of a low sample size and a lack of control, the rate of post-COVID-19 complications after treatment with plitidepsin is in the low range of published reports. (ClinicalTrials.gov Identifier: NCT05121740; https://clinicaltrials.gov/ct2/show/NCT05121740).
The effect of interest and attitude on public comprehension of news with data visualization
Authors: Sánchez-Holgado Patricia , Arcila-Calderón Carlos , Frías-Vázquez Maximiliano
Published: February 2023

In recent years, data visualization has been gaining space in journalism, not only in the specialized press, but also in the general press. The objective of this article is to analyze whether there are differences between the impact of receiving a traditional news item and that of a news item with data visualization, in terms of interest, comprehension and attitudes toward data visualization. For this, a study (N = 700) was carried out with two experimental conditions (traditional news vs. news with data visualization), using scientific and health communication news. Moderated mediation analysis were performed to understand how data visualization affects factors such as attitude, or interest, and affects public comprehension. The results showed significant indirect effects that indicate that reading a data visualization news item increases comprehension and, with it, positive attitudes toward data visualization. Variables related to comprehension and interest have been found to have a significant impact on attitudes toward data viewing, opening new lines of research to delve into the factors that affect data-driven news performance.
Learning meaningful latent space representations for patient risk stratification: Model development and validation for dengue and other acute febrile illness
Authors: Hernandez Bernard , Stiff Oliver , Ming Damien K. , Ho Quang Chanh , Nguyen Lam Vuong , Nguyen Minh Tuan , Nguyen Van Vinh Chau , Nguyen Minh Nguyet , Nguyen Quang Huy , Phung Khanh Lam , Dong Thi Hoai Tam , Dinh The Trung , Huynh Trung Trieu , Wills Bridget , Simmons Cameron P. , Holmes Alison H. , Yacoub Sophie , Georgiou Pantelis ,   on behalf of the Vietnam ICU Translational Applications Laboratory (VITAL) investigators
Published: February 2023

Background

Increased data availability has prompted the creation of clinical decision support systems. These systems utilise clinical information to enhance health care provision, both to predict the likelihood of specific clinical outcomes or evaluate the risk of further complications. However, their adoption remains low due to concerns regarding the quality of recommendations, and a lack of clarity on how results are best obtained and presented.

Methods

We used autoencoders capable of reducing the dimensionality of complex datasets in order to produce a 2D representation denoted as latent space to support understanding of complex clinical data. In this output, meaningful representations of individual patient profiles are spatially mapped in an unsupervised manner according to their input clinical parameters. This technique was then applied to a large real-world clinical dataset of over 12,000 patients with an illness compatible with dengue infection in Ho Chi Minh City, Vietnam between 1999 and 2021. Dengue is a systemic viral disease which exerts significant health and economic burden worldwide, and up to 5% of hospitalised patients develop life-threatening complications.

Results

The latent space produced by the selected autoencoder aligns with established clinical characteristics exhibited by patients with dengue infection, as well as features of disease progression. Similar clinical phenotypes are represented close to each other in the latent space and clustered according to outcomes broadly described by the World Health Organisation dengue guidelines. Balancing distance metrics and density metrics produced results covering most of the latent space, and improved visualisation whilst preserving utility, with similar patients grouped closer together. In this case, this balance is achieved by using the sigmoid activation function and one hidden layer with three neurons, in addition to the latent dimension layer, which produces the output (Pearson, 0.840; Spearman, 0.830; Procrustes, 0.301; GMM 0.321).

Conclusion

This study demonstrates that when adequately configured, autoencoders can produce two-dimensional representations of a complex dataset that conserve the distance relationship between points. The output visualisation groups patients with clinically relevant features closely together and inherently supports user interpretability. Work is underway to incorporate these findings into an electronic clinical decision support system to guide individual patient management.
Functionalized calcium phosphate nanoparticles to direct osteoprotegerin to bone lesion sites in a medaka (Oryzias latipes) osteoporosis model
Authors: Imangali Nurgul , Sokolova Viktoriya , Kostka Kathrin , Epple Matthias , Winkler Christoph
Published: February 2023

Calcium phosphate (CaP) is the inorganic part of hard tissues, such as bone, teeth and tendons, and has a high biocompatibility and good biodegradability. Therefore, CaP nanoparticles functionalized with DNA encoding bone anabolic factors are promising carrier-systems for future therapeutic development. Here, we analysed CaP nanoparticles in a genetically modified medaka fish model, where osteoporosis-like lesions can be induced by transgenic expression of receptor activator of nuclear factor kappa-B ligand (Rankl). Rankl-transgenic medaka were used to visualize and understand effects of microinjected functionalized CaP nanoparticles during modulation of osteoclast activity in vivo. For this, we synthetized multi-shell CaP nanoparticles by rapid precipitation of calcium lactate and ammonium hydrogen phosphate followed by the addition of plasmid DNA encoding the osteoclastogenesis inhibitory factor osteoprotegerin-b (Opgb). An additional layer of poly(ethyleneimine) was added to enhance cellular uptake. Integrity of the synthesized nanoparticles was confirmed by dynamic light scattering, scanning electron microscopy and energy dispersive X-ray spectroscopy. Fluorescently labelled CaP nanoparticles were microinjected into the heart, trunk muscle or caudal fins of Rankl-transgenic medaka embryos that expressed fluorescent reporters in various bone cell types. Confocal time-lapse imaging revealed a uniform distribution of CaP nanoparticles in injected tissues and showed that nanoparticles were efficiently taken up by macrophages that subsequently differentiated into bone-resorbing osteoclasts. After Rankl induction, fish injected with Opg-functionalized nanoparticles showed delayed or absent degradation of mineralized matrix, i.e. a lower incidence of osteoporosis-like phenotypes. This is proof of principle that CaP nanoparticles can be used as carriers to efficiently deliver modulatory compounds to osteoclasts and block their activity.
Altered GnRH neuron and ovarian innervation characterize reproductive dysfunction linked to the Fragile X messenger ribonucleoprotein (Fmr1) gene mutation
Authors: Villa Pedro A. , Lainez Nancy M. , Jonak Carrie R. , Berlin Sarah C. , Ethell Iryna M. , Coss Djurdjica
Published: February 2023

Introduction

Mutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene cause Fragile X Syndrome, the most common monogenic cause of intellectual disability. Mutations of FMR1 are also associated with reproductive disorders, such as early cessation of reproductive function in females. While progress has been made in understanding the mechanisms of mental impairment, the causes of reproductive disorders are not clear. FMR1-associated reproductive disorders were studied exclusively from the endocrine perspective, while the FMR1 role in neurons that control reproduction was not addressed.

Results

Here, we demonstrate that similar to women with FMR1 mutations, female Fmr1 null mice stop reproducing early. However, young null females display larger litters, more corpora lutea in the ovaries, increased inhibin, progesterone, testosterone, and gonadotropin hormones in the circulation. Ovariectomy reveals both hypothalamic and ovarian contribution to elevated gonadotropins. Altered mRNA and protein levels of several synaptic molecules in the hypothalamus are identified, indicating reasons for hypothalamic dysregulation. Increased vascularization of corpora lutea, higher sympathetic innervation of growing follicles in the ovaries of Fmr1 nulls, and higher numbers of synaptic GABAA receptors in GnRH neurons, which are excitatory for GnRH neurons, contribute to increased FSH and LH, respectively. Unmodified and ovariectomized Fmr1 nulls have increased LH pulse frequency, suggesting that Fmr1 nulls exhibit hyperactive GnRH neurons, regardless of the ovarian feedback.

Conclusion

These results reveal Fmr1 function in the regulation of GnRH neuron secretion, and point to the role of GnRH neurons, in addition to the ovarian innervation, in the etiology of Fmr1-mediated reproductive disorders.
New horizons in human sperm selection for assisted reproduction
Authors: Nixon Brett , Schjenken John E. , Burke Nathan D. , Skerrett-Byrne David A. , Hart Hanah M. , De Iuliis Geoffry N. , Martin Jacinta H. , Lord Tessa , Bromfield Elizabeth G.
Published: February 2023

Male infertility is a commonly encountered pathology that is estimated to be a contributory factor in approximately 50% of couples seeking recourse to assisted reproductive technologies. Upon clinical presentation, such males are commonly subjected to conventional diagnostic andrological practices that rely on descriptive criteria to define their fertility based on the number of morphologically normal, motile spermatozoa encountered within their ejaculate. Despite the virtual ubiquitous adoption of such diagnostic practices, they are not without their limitations and accordingly, there is now increasing awareness of the importance of assessing sperm quality in order to more accurately predict a male’s fertility status. This realization raises the important question of which characteristics signify a high-quality, fertilization competent sperm cell. In this review, we reflect on recent advances in our mechanistic understanding of sperm biology and function, which are contributing to a growing armory of innovative approaches to diagnose and treat male infertility. In particular we review progress toward the implementation of precision medicine; the robust clinical adoption of which in the setting of fertility, currently lags well behind that of other fields of medicine. Despite this, research shows that the application of advanced technology platforms such as whole exome sequencing and proteomic analyses hold considerable promise in optimizing outcomes for the management of male infertility by uncovering and expanding our inventory of candidate infertility biomarkers, as well as those associated with recurrent pregnancy loss. Similarly, the development of advanced imaging technologies in tandem with machine learning artificial intelligence are poised to disrupt the fertility care paradigm by advancing our understanding of the molecular and biological causes of infertility to provide novel avenues for future diagnostics and treatments.
The manufacturers’ strategy selection of carbon emission reduction and pricing under carbon trading policy and consumer environmental awareness
Authors: Dai Yao , Wu Hongliang , Pan Helin , Luo Lijian
Published: February 2023

Carbon trading policy and consumer environmental awareness are increasingly important to manufacturers’ carbon emission reduction and pricing. To analyze their strategy selection of carbon emission reduction and pricing, this paper develops three game models, where two manufacturers could choose no cooperation (NC), only cooperation in carbon emission reduction (SC), or simultaneous cooperation in carbon emission reduction and pricing (CC). By solving these models and comparing their environmental R&D levels, net carbon emissions, and profits, the paper finds strategy selection for manufacturers and its conditions. Results show that from the view of the environmental R&D level and supply chain’s profit, NC and SC may be the optimal strategy and the second-best strategy, respectively. From the net carbon emission point of view, CC and SC should be the optimal strategy and the second-best strategy, respectively. As to manufacturers’ profits, CC should be the optimal strategy, and NC or SC should be the second-best strategy. From comprehensive views, none of these strategies could be the optimal strategy, but SC may be the second-best strategy. This paper contributes in three aspects. First, this paper designs three strategies of carbon emission reduction and pricing for two manufacturers. Second, this paper takes the initial carbon emission allowances of the government as one of decision variables. Finally, this paper investigates the effects of different strategies and finds strategy selections for manufacturers from a single view and comprehensive views.
The biomarkers related to immune infiltration to predict distant metastasis in breast cancer patients
Authors: Ren Chengsi , Gao Anran , Fu Chengshi , Teng Xiangyun , Wang Jianzhang , Lu Shaofang , Gao Jiahui , Huang Jinfeng , Liu Dongdong , Xu Jianhua
Published: February 2023

Background: The development of distant metastasis (DM) results in poor prognosis of breast cancer (BC) patients, however, it is difficult to predict the risk of distant metastasis.

Methods: Differentially expressed genes (DEGs) were screened out using GSE184717 and GSE183947. GSE20685 were randomly assigned to the training and the internal validation cohort. A signature was developed according to the results of univariate and multivariate Cox regression analysis, which was validated by using internal and external (GSE6532) validation cohort. Gene set enrichment analysis (GSEA) was used for functional analysis. Finally, a nomogram was constructed and calibration curves and concordance index (C-index) were compiled to determine predictive and discriminatory capacity. The clinical benefit of this nomogram was revealed by decision curve analysis (DCA). Finally, we explored the relationships between candidate genes and immune cell infiltration, and the possible mechanism.

Results: A signature containing CD74 and TSPAN7 was developed according to the results of univariate and multivariate Cox regression analysis, which was validated by using internal and external (GSE6532) validation cohort. Mechanistically, the signature reflect the overall level of immune infiltration in tissues, especially myeloid immune cells. The expression of CD74 and TSPAN7 is heterogeneous, and the overexpression is positively correlated with the infiltration of myeloid immune cells. CD74 is mainly derived from myeloid immune cells and do not affect the proportion of CD8+T cells. Low expression levels of TSPAN7 is mainly caused by methylation modification in BC cells. This signature could act as an independent predictive factor in patients with BC (p = 0.01, HR = 0.63), and it has been validated in internal (p = 0.023, HR = 0.58) and external (p = 0.0065, HR = 0.67) cohort. Finally, we constructed an individualized prediction nomogram based on our signature. The model showed good discrimination in training, internal and external cohort, with a C-index of 0.742, 0.801, 0.695 respectively, and good calibration. DCA demonstrated that the prediction nomogram was clinically useful.

Conclusion: A new immune infiltration related signature developed for predicting metastatic risk will improve the treatment and management of BC patients.
Identifification and validation of ferroptosis signatures and immune infifiltration characteristics associated with intervertebral disc degeneration
Authors: Zhang Feng , Cui Di , Wang Kangkang , Cheng Huimin , Zhai Yunlei , Jiao Wei , Wang Zhaodong , Cui Xilong , Yu Haiyang
Published: February 2023

Ferroptosis and immune infiltration play an important role in the pathogenesis of intervertebral disc degeneration (IDD). However, there is still a lack of comprehensive analysis on the interaction between ferroptosis-related genes (FRGs) and immune microenvironment in IDD patients. Therefore, this study aims to explore the correlation between FRGs characteristics and immune infiltration in the progression of IDD. The expression profiles (GSE56081 and GSE70362) and FRGs were downloaded from the comprehensive gene expression omnibus (GEO) and FerrDb database, respectively, and the differences were analyzed using R. The intersection of IDD related differential genes (DEGs) and FRGs was taken as differentially expressed FRGs (DE-FRGs) and GO and KEGG enrichment analysis was conducted. Then, we used least absolute shrinkage and selection operator (LASSO) regression algorithm and support vector machine (SVM) algorithm to screen feature genes and draw ROC curve judge the diagnostic value of key DE-FRGs. Then CIBERSORT algorithm is used to evaluate the infiltration of immune cells and analyze the correlation between key DE-FRGs and immune infiltration. Based on the analysis results, we conducted single gene GSEA analysis on key DE-FRGs. RT-PCR and immunohistochemistry further verified the clinical value of the results of biochemical analysis and screening. Seven key DE-FRGs were screened, including the upregulated genes NOX4 and PIR, and the downregulated genes TIMM9, ATF3, ENPP2, FADS2 and TFAP2A. Single gene GSEA analysis further elucidates the role of DE-FRGs in IDD associated with ferroptosis. Correlation analysis showed that seven key DE-FRGs were closely related to immune infiltration in the development of IDD. Finally, RT-PCR and immunohistochemical staining showed that NOX4, ENPP2, FADS2 and TFAP2A were statistically significant differences. In this study, we explored the connection between ferroptosis related characteristics and immune infiltration in IDD, and confirmed that NOX4, ENPP2, FADS2, and TFAP2A may become biomarkers and potential therapeutic targets for IDD.
Interferon therapy and its association with depressive disorders – A review
Authors: Lai Jing Yung , Ho Jian Xiang , Kow Audrey Siew Foong , Liang Gengfan , Tham Chau Ling , Ho Yu-Cheng , Lee Ming Tatt
Published: February 2023

Interferons (IFNs) are important in controlling the innate immune response to viral infections. Besides that, studies have found that IFNs also have antimicrobial, antiproliferative/antitumor and immunomodulatory effects. IFNs are divided into Type I, II and III. Type I IFNs, in particular IFN-α, is an approved treatment for hepatitis C. However, patients developed neuropsychological disorders during treatment. IFN-α induces proinflammatory cytokines, indoleamine 2,3-dioxygenase (IDO), oxidative and nitrative stress that intensifies the body’s inflammatory response in the treatment of chronic inflammatory disease. The severity of the immune response is related to behavioral changes in both animal models and humans. Reactive oxygen species (ROS) is important for synaptic plasticity and long-term potentiation (LTP) in the hippocampus. However, excess ROS will generate highly reactive free radicals which may lead to neuronal damage and neurodegeneration. The limbic system regulates memory and emotional response, damage of neurons in this region is correlated with mood disorders. Due to the drawbacks of the treatment, often patients will not complete the treatment sessions, and this affects their recovery process. However, with proper management, this could be avoided. This review briefly describes the different types of IFNs and its pharmacological and clinical usages and a focus on IFN-α and its implications on depression.
HIV associated cell death: Peptide-induced apoptosis restricts viral transmission
Authors: Chen Qiongyu , Zhao Yan , Zhang Yonghong , Zhang Jianbo , Lu Wenshu , Chang Chih-Hao , Jiang Shisong
Published: February 2023

The human immunodeficiency virus (HIV) is still a global pandemic and despite the successful use of anti-retroviral therapy, a well-established cure remains to be identified. Viral modulation of cell death has a significant role in HIV pathogenesis. Here we sought to understand the major mechanisms of HIV-induced death of lymphocytes and the effects on viral transmission. Flow cytometry analysis of lymphocytes from five latent HIV-infected patients, and HIV IIIB-infected MT2 cells demonstrated both necrosis and apoptosis to be the major mechanisms of cell death in CD4+ and CD4-/CD8- lymphocytes. Significantly, pro-apoptotic tumor necrosis factor (TNF) peptide (P13) was found to inhibit HIV-related cell death and reduced viral transmission. Whereas pro-necrotic TNF peptide (P16) had little effect on HIV-related cell death and viral transmission. Understanding mechanisms by which cell death can be manipulated may provide additional drug targets to reduce the loss of CD4+ cells and the formation of a viral reservoir in HIV infection.
The use of bioinformatics methods to identify the effects of SARS-CoV-2 and influenza viruses on the regulation of gene expression in patients
Authors: Sun Zhongyi , Ke Li , Zhao Qiuyue , Qu Jiachen , Hu Yanan , Gao Han , Peng Zhiyong
Published: February 2023

Background

SARS-CoV-2 infection is a respiratory infectious disease similar to influenza virus infection. Numerous studies have reported similarities and differences in the clinical manifestations, laboratory tests, and mortality between these two infections. However, the genetic effects of coronavirus and influenza viruses on the host that lead to these characteristics have rarely been reported.

Methods

COVID-19 (GSE157103) and influenza (GSE111368, GSE101702) datasets were downloaded from the Gene Expression Ominbus (GEO) database. Differential gene, gene set enrichment, protein-protein interaction (PPI) network, gene regulatory network, and immune cell infiltration analyses were performed to identify the critical impact of COVID-19 and influenza viruses on the regulation of host gene expression.

Results

The number of differentially expressed genes in the COVID-19 patients was significantly higher than in the influenza patients. 22 common differentially expressed genes (DEGs) were identified between the COVID-19 and influenza datasets. The effects of the viruses on the regulation of host gene expression were determined using gene set enrichment and PPI network analyses. Five HUB genes were finally identified: IFI27, OASL, RSAD2, IFI6, and IFI44L.

Conclusion

We identified five HUB genes between COVID-19 and influenza virus infection, which might be helpful in the diagnosis and treatment of COVID-19 and influenza. This knowledge may also guide future mechanistic studies that aim to identify pathogen-specific interventions.