bluuebunny/crossref_metadata_2025 huggingface dataset:
Students' Critical Thinking on Argumentative Essay Writing through Cooperative Learning
Authors: Romadhoni Mohammad , Ruqoyyah Amilia Andania  , Ai-Chun Yen
Published: November 2022

Carried on in non-English major freshman students setting, this study aims to examine how critical thinking skills can be developed through cooperative learning in their argumentative essay writing. An experimental group (n=20) and a control group (n=20) were randomly set up, the students were pre-tested and post-tested to see if there is a significant difference in their assigned essay through the Illinois Critical Thinking Essay Scoring Rubric. The implementation of critical thinking rubrics was carried out by 1) supporting students in cooperation, 2) offering the objective 3) fostering students to develop their ideas in writing. The Paired Sample T-test was used to calculate the difference between the pre-and post-test results. Results confirmed that in the Paired Sample t-test, the mean score (-5000) of the experimental group is statistically higher than the mean of the control group’s (-3900). It indicates that the implementation of the critical thinking strategy effectively develops and promotes students’ critical thinking skills in argumentative essay writing. Through the implementation of five key elements of critical thinking by Sadeghi (2012), students were more open-minded, tolerant, objective, honest and concise, respecting others, and interpreting situations differently. The research offered a different perspective on developing students’ critical thinking strategy use by focusing on longer periods of research and the larger number of participants and also implied the integration of critical thinking scoring rubric and argumentative essay skill performance for future research.
Students’ Perception of Using Telegram in Learning English at SMK Negeri 1 Bandar Masilam
Authors: Br Depari Marisa Yunita , Devi Liza Sri , Sianipar Ester , Herman Herman
Published: November 2022

This study is related to qualitative and uses a questionnaire method used by teachers and students when learning English in the classroom. The formulation of the problem is: Types of learning English by using telegram media which is used in the process of learning English for class X TKJ 1 SMK Negeri 1 Bandar Masilam students. This research uses qualitative research. The purpose of this study was to find out how the students of SMK Negeri 1 Bandar Masilam felt about using Telegram to learn English and how easy it was to use it. Telegram is one of the learning media. Telegram is a well-known tool in the education sector, especially at the college level. Telegram is used by some teachers as a learning medium. Telegram in language learning is being studied using qualitative research methods and questionnaire instruments. Twenty students from SMK Negeri 1 Bandar Masilam Class X Tkj-1 will take part in the lesson. Research and discussion showed that students' perceptions of the use of Telegram had a positive response. Most students agree that Telegam is easy to use and helps students learn English by allowing them to save and retrieve assignments and, in the case of Telegram, submit assignments. As a result, using Telegram to learn English is a wise decision
A Review on Cosmetic Formulations and Physicochemical Characteristics of Emollient and Day Cream Using Vegetable Based-Wax Ester
Authors: Nooratiqah Azmi  , Salina Mat Radzi  , Maryam Mohamed Rehan  , Nur Amalina Mohd Amin
Published: November 2022

The cosmetic sector is one of the fastest-growing industries and continuously evolving as new technology is established. Skincare, haircare, make-up, and body care items were among the products available. Cosmetic formulas have progressed in recent years, allowing for the creation of more beneficial cosmetics. In chemistry, solids, liquids, and gases are primarily physicochemical characteristics. These are typically determined by a density, refractive index (RI), oxidation state, and vibrational frequency measurement. Physical and chemical qualities show a distinct feature that aids in the formulation of an enhanced emollient and day cream. This paper focuses on physicochemical   characteristics such as RI, saponification value (SV), iodine value (IV), and acid value (AV). As for this review, the use of synthesised vegetable-based wax ester was utilised to formulate emollient and day cream. The esterification of vegetable-based waxes was performed by synthesising oleic acid from vegetable-based products and oleyl alcohol in the solvent.
Islamic Historical Figures Drama as A Tool in Promoting Islamic Virtues
Authors: Md Isa Noor Shamsarini , Kamarudin Mohd Fadhil , Hairul Anuar Inda Murni
Published: November 2022

Negative perception towards Islam is a controversial and highly debated issue in the world today but only minimal effort has been done to combat the misconception. While there are many issues that surround the Muslim ummah, the loss of “adab” due to the confusion of knowledge has been the main culprit in advancing moral collapse crisis across the globe. Perfection of character through “adab” is the main focus in Islamic philosophy. To rectifies the issue; the media need to be at the forefront of educating the community on the real face of Islam. Looking at the success of a few Islamic-theme-series particularly "Umar Al-Khattab" gives us hope in promoting the virtues and principles of Islam through Islamic historical dramas or movies especially in the context of Malaysia and Southeast Asia. Content analysis method was used to analyse “adab” from the Umar Al Khattab series. “Adab” or virtue is related to the teachings of Islam which by further understanding the virtues can be educational to the viewers. Bringing back the identity as a Muslim can be done at the core level by restoring faith in an individual by showcasing the influential individuals in Islam through dramas or films because media are powerful tools in changing people's opinion and way of thinking.
Defining and Exploring the Dimensionality of ‘Halal-Hotel’ Concept
Authors: Harith Izwan , Abu Hasan Nurul Nadirah , Mior Kamarulbaid Afiqah , Mohd Sofian Muhammad Raqib
Published: November 2022

Islamic tourism highlights the growing importance of what for many may be an untapped and unknown market. With one billion followers across 57 countries, Islam’s role in tourism is important to tourism and hospitality managers in both Muslim and non-Muslim countries. Consequently, government policies, strategies and programs have laid undue emphasis on the growth of ‘Halal-Hotel’; a total Islamic accommodation standard that prescribes by Islamic rules. Halal is fast gaining worldwide recognition and this is not merely because the Muslim Ummah is growing in number, but more significantly, because halal is being recognized as a new benchmark for safety and quality assurance. Unfortunately, there are ambiguities pertaining the criteria for ‘halal hotel’ in the hotel sector because the lack of consensus among stakeholders within the Muslim-friendly tourism and hospitality (MFT) sector in Malaysia. Furthermore, The translation of Arabic-Islamic terminology into Malay language may offer its advantages as well as challenges to all relevant tourism stakeholders within the Muslim-friendly tourism and hospitality (MFT) sector in Malaysia. In terminology translation, equivalents in the target language are usually preferred to be as concise as possible and able to maintain existing morphological and semantic relationship between the translated terms and other morphologically and semantically related source language terms. Moreover, researchers and hotel operators have struggled to arrive to an agreement as to what is the most appropriate term or concept that could best and comprehensively describe a hotel that operates according to the Islamic rules and regulations. Therefore, this research aims to identify the dimensionality of ‘halal hotel’ concepts and to explore the suitability of adopting the ‘halal hotel’ as the term to be use among the Muslim-friendly tourism and hospitality (MFT) sector in Malaysia. A qualitative research method is chosen to conduct this research, and the samples are from the stakeholders which consist of Islamic scholars, hotel operator and the hotel’s guest.
Advanced Development of Bio-fertilizer Formulations Using Microorganisms as Inoculant for Sustainable Agriculture and Environment – A Review
Authors: Nur Maisarah Mohamad Sarbani  , Yahaya Nazariyah
Published: November 2022

Conventional types of fertilizer such as chemical and synthetic fertilizers have demonstrated various adverse effects on the environment, crops, and humans. The utilization of plant probiotics as a bio-fertilizer in agriculture has been recognized to benefit the growth of the plant and inhibit the activity of plant pathogens. Traditional formulations of bio-fertilizer have provided insight into the beneficial use of microorganisms in crops. Despite its advantage to the environment, the effectiveness of traditional bio-fertilizer is common as compared to chemical fertilizer. Thus, a variety of bio-fertilizer formulations have been developed to improve the success rate of bio-fertilizer in increasing plant productivity. This review was focused on the development of bio-fertilizer formulation and the potential of bio-fertilizer to substitute chemical fertilizer application. In addition, this research review was also undertaken with a great demand on producing low cost and highly effective fertilizer without harming the environment and humans. Thus, the advantages and disadvantages of each formulation type have also been reviewed, emphasizing the perspective of bio-fertilizer and their suitability as bio-fertilizer as a substitute for chemical fertilizers in sustainable agriculture.
Modeling of Thermal Preparation of Shock Absorbers of Trucks
Authors: Chernukhin Roman V.
Published: November 2022

The use of modern materials and technical fluids allows you to operate cars at negative temperatures, but in some regions of the world (for example, in Siberia), the ambient air temperature can fall below 243 K for several weeks or even months. The operation of trucks at such a temperature refers to extreme conditions that force the special preparation of equipment. This preparation consists not only of special maintenance, but also of carrying out some activities that are carried out immediately before starting the engine and driving. The essence of these measures is, among other things, the thermal preparation of the components and assemblies of the vehicle before departure.This work is devoted to the thermal preparation of truck shock absorbers. It is revealed that the use of oils, the kinematic viscosity of which significantly depends on the ambient temperature, is a limiting factor in the winter operation of shock absorbers. The simulation of the operation of electric flexible heaters for shock absorbers in the SolidWorks Flow Simulation environment was carried out and the preheating efficiency was evaluated. It is established that the temperature distribution of the shock absorber fluid during heating of two-pipe shock absorbers occurs unevenly, but despite this, preheating significantly improves the characteristics of shock absorbers and contributes to the safe and long-lasting operation of trucks.
Pengembangan Strategi Pemasaran Pada PT. Dodol Bhineka Dalam Meningkatkan Penjualan
Authors: Cahyadi Ujang , Pratama Aldi Ardiansyah
Published: November 2022

Perkembangan dunia industry di era globalisasi mengalami perkembangan yang sangat pesat dengan persaingan bisnis yang sangat ketat, di era globalisasi ini sector industry mengalami situasi yang sulit. Tujuan dalam penelitian ini yaitu mengetahui mengenai strategi penjualan yang diterapkan oleh objek yaitu PD. Dodol Bhineka dalam memaksimalkan penjualan dodol. Penelitian yang dilakukan oleh peneliti yaitu menggunakan pendekatan metode deskriptif dengan metode kualitatif, dengan menggunakan teknik wawancara baik terhadap pemilik pabrik maupun karyawan. Metode yang mendukung dalam menyelesaikan permasalahan yang terjadi yaitu peneliti menggunakan metode analisis SWOT dan AHP. Berdasarkan hasil dari penelitian, penempatan posisi perusahaan yang berada pada kuadran I di matriks kuadran SWOT yang menjelaskan mengenai peluang dan kekuatan besar yang akan memanfaatkan peluang yang ada.
Evaluasi Human Error Penyebab Kecacatan Produksi pada Usaha Konveksi Manda Hijab Cicalengka
Authors: Mauluddin Yusuf , Azzahra Fithria
Published: November 2022

Konveksi Manda Hijab Cicalengka merupakan salah satu UMKM dalam bidang fashion yang memproduksi kerudung. Kecacatan sering terjadi akibat kesalahan-kesalahan dari operator produksinya. Ditinjau dari penelitian pendahuluan kegagalan yang sering terjadi disebabkan oleh kelalaian manusia. Hal ini menjadi penyebab utama yang sangat mempengaruhi kegagalan produk tersebut. Penelitian ini bertujuan untuk mendapatkan hasil identifikasi penyebab terjadinya human error dan rencana penanggulangannya. Upaya untuk mengurangi kecacatan yang terjadi perlu dilakukan identifikasi untuk meneliti faktor-faktor dari kesalahan yang dilakukan oleh operator tersebut menggunakan salah satu metode penilaian keandalan manusia yaitu SHERPA dan HEART. Hasil dari penelitian ini, diketahui probabilitas human error yang dapat terjadi pada proses quality control yaitu sebesar 12%, pada proses pemolaan dan sampling yaitu sebesar 16%, pada proses spreading dan pemotongan (cutting) yaitu sebesar 17%, pada proses plisket yaitu sebesar 18%, pada proses menjahit (sewing) yaitu sebesar 21%, pada proses finishing dan packaging yaitu sebesar 16%. Nilai persentase human error tertinggi yaitu terdapat pada proses produksi menjahit kerudung yaitu sebesar 21%. Penentuan rencana perbaikan berguna untuk memberi saran perbaikan agar segala kegiatan yang merupakan error dapat diminimalisir dan dapat menurunkan tingkat kecacatan pada proses produksi kerudung. Hasil penelitian ini diberikan sebagai masukan perusahaan, salah satu upaya pencegahan terjadinya kecacatan atau kegagalan pada proses produksi dibuat Standar Operasional Prosedur (SOP) untuk efisiensi kerja, menyamakan standar kualitas kerja dan output yang dihasilkan, sekaligus meminimalisir kegagalan dan miskomunikasi. Pembuatan SOP menjahit sebagai bentuk pencegahan kecacatan yang sering terjadi pada saat proses menjahit berlangsung.
Meningkatkan Kreativitas Anak melalui Media Bahan Bekas
Authors: Cicik Setyowati
Published: November 2022

Dunia anak adalah dunia bermain, dan belajar yang melibatkan semua panca indera. Bermain identik dengan kegiatan yang menyenangkan, menggembirakan, serta dipenuhi suasana suka dan ceria. Dalam bermain, permainan yang dipilih biasanya yang sesuai dengan kehendak hati, sesuai harapan, serta mendatangkan keceriaan. Bermain yang dilakuhkan anak membutuhkan alat dan bahan penunjang. Salah satu sarana penunjang pembelajaran itu dengan sumber belajar anak di TK, RA maupun KB. Sumber belajar anak TK, Ra maupun KB adalah penggunaan alat pendidikan edukatif atau yang lebih dikenal dengan APE. Alat atau media pembelajaran dapat dibuat sendiri dengan bahan yang mudah dicari tanpa harus selalu membeli dan dengan penggunaan bahan bekas tersebut dapat membantu mengurangi pencemaran ekosistem pada tanah. Selain kita membantu anak dalam belajar sekaligus kita mengajarkan anak untuk dapat memanfaatkan berbagai sampah atau bahan bekas di sekitar kita untuk dijadikan barang yang bermanfaat. Pemanfaatan sampah akan dapat maksimal jika dikekola dan di inovasikan sesuai dengan jenis dan kegunaannya.
Penggunaan Media Bahan Alam untuk Meningkatkan Kemampuan Berhitung pada Anak Usia 5-6 Tahun
Authors: Lestari Briyantika puji , Amala Nisael
Published: November 2022

Kegiatan Pengembangan pembelajaran matematika untuk anak usia dini dirancang agar anak mampu menguasai berbagai pengetahuan dan keterampilan matematika yang mendukung mereka untuk hidup dan bekerja pada masa mendatang yang pada kemampuan memecahkan masalah. Begitu pentingnya kemampuan berhitung bagi manusia, maka kemampuan berhitung ini perlu diajarkan sejak dini. Kemampuan berhitung sebaiknya diberikan pada anak dengan suasana yang menyenangkan dan memberikan rasa aman serta kebebasan bagi anak. Masalah ini dihadapi oleh anak di lembaga TK Dharma Wanita Ketanon dari 13 anak capaian kognitif terkait kemampuan berhitung hanya 2 anak yang memperoleh BSH sedangkan 9 anak dalam kategori MB dan 2 anak BB. Dari analisis kebutuhan kebutuhan ditemukan media pembelajaran yang dapat menumbuhkan minat anak untuk mencapai kemamupuan berhitung. Jenis penelitian adalah Penelitian Tindakan Kelas dengan menggunakan 3 siklus. Hasil penelitian ini diterima dan dapat dibuktikan bahwa pada siklus ke I diperoleh prosentase ketuntasan 30,7%, pada siklus II diperoleh prosentase ketuntasan 61,5% dan pada siklus ke III diperoleh prosentase ketuntasan 84,6%.

Activities Development of learning mathematics for early childhood is designed so that children are able to master a variety of mathematical knowledge and skills that will enable them to live and work in the future which emphasizes problem solving skills. So important is the ability to count for humans, then this ability to count needs to be taught from an early age. The ability to count should be given to children in a pleasant atmosphere and provide a sense of security and freedom for children. This problem was faced by children in the Dharma Wanita Ketanon Kindergarten institution, out of 13 children with cognitive achievement related to numeracy skills, only 2 children received BSH while 9 children in the MB category and 2 BB children. From the needs analysis, it was found the need for learning media that can foster children's interest in achieving numeracy skills. The type of research is Classroom Action Research using 3 cycles. The results of this study are accepted and can be proven that in the first cycle the percentage of completeness is 30.7%, in the second cycle the percentage of completeness is 61.5% and in the third cycle the percentage of completeness is 84.6%.
PENERAPAN MODEL PEMBELAJARAN KOOPERATIF TIPE THINK PAIR SHARE UNTUK MENINGKATKAN PEMAHAMAN KONSEP SISWA
Authors: Fransiska Fransiska , Maizora Syafdi , Yensy Nurul Astuty
Published: November 2022

Penelitian ini bertujuan untuk mengetahui cara meningkatkan pemahaman konsep matematika siswa pada materi lingkaran dengan menerapkan model pembelajaran kooperatif tipe Think Pair Share. Jenis penelitian ini adalah Penelitian Tindakan Kelas (PTK) dengan teknik pengumpulan data melalui tes pemahaman konsep. Hasil penelitian menunjukkan bahwa penerapan model pembelajaran kooperatif tipe Think Pair Share dapat meningkatkan pemahaman konsep matematika siswa kelas VIII C SMPN 7 Kota Bengkulu. Pemahaman konsep ditingkatkan dengan peserta didik belajar dengan media Lembar Kerja Peserta Didik (LKPD), soal latihan yang memuat indikator pemahaman konsep dan diberikan bimbingan kepada peserta didik yang mengalami kesulitan dalam menyelesaikan LKPD dan memahami materi. Persentase pencapaian seluruh peserta didik untuk setiap indikator pemahaman konsep dari pra siklus hingga siklus I secara berturut-turut yaitu 46,09%;61,22% dengan pencapaian tiap indikator yaitu ; (1) menyatakan ulang konsep : 57,14%;69,09%. (2) mengklarifikasi objek atau sifat sesuai konsepnya : 60,71%;85,71%. (3) memberikan contoh dan bukan contoh : 80,95%;88,1%. (4) menyajikan konsep dalam bentuk representasi matematis : 53,37%;66,67% (5) mengembangkan syarat perlu atau syarat cukup : 33,33%;70,24%. (6) menggunakan atau memanfaatkan operasi tertentu : 15,47%;17,86%. (7) mengaplikasikan konsep dan algoritma dalam pemecahan masalah 21,43%; 30,85%.
Stratified K-fold cross validation optimization on machine learning for prediction
Authors: Widodo Slamet , Brawijaya Herlambang , Samudi Samudi
Published: November 2022

Cervical is the second most common malignant tumor in women, with 341,000 deaths worldwide in 2020, almost 80% of which occur in developing countries. One of the causes is infection with Human papillomavirus (HPV) types 16 and 18. The increasing incidence of cervical cancer in Indonesia makes this disease must be treated seriously because it is one of the main causes of death. In addition to the virus, external factors can be one of the causes. The high mortality rate in patients is caused by the patient's awareness of the emergence of cervical cancer which is only seen when it enters the final stage. One of the efforts to reduce the number of sufferers is to implement cervical cancer detection. Early detection of cervical cancer can also be identified by looking at external factors, such as behavioral factors, intentions, attitudes, norms, perceptions, motivations, social support, and empowerment. However, the data used has an imbalance in the distribution of the target class, namely more negative samples than positive ones. To overcome this, a technique called Stratified K-Fold Cross-Validation (SKCV) is used. Evaluation of the accuracy value using the Confusion matrix to determine the performance of each model. The best performance of the five classification algorithms used is 96 percent (RF), 94 percent (LR), 92 percent (XGBoost), 90 percent (KNN), and 88 percent (NB). The results show that the model formed by RF-based SKCV has the highest accuracy of other models.
Endoscopic Resection of Inverted Papilloma in the Maxillary Sinus - ‘Prelacrimal Approach,’ ‘Origin Site Cauterization and Drilling (Painting and Washing)’
Authors: Kim Seo Young , Won Tae-Bin
Published: November 2022

Inverted papilloma is a common, benign sinonasal tumor with a known high rate of recurrence. To prevent recurrences, complete excision of inverted papilloma is essential. In complete excision, especially, identifying the attachment site of the tumor and managing the site meticulously is important. In this study, we introduce two surgical methods for complete excision of inverted papilloma that can reduce the recurrence rate: the prelacrimal approach and the ‘origin site cauterization and drilling (painting and washing)’ approach.
Risk Factors for Recurrence Free Survival in Patients With Parotid Gland Cancer: 10-Year Single Center Experience
Authors: Kim Sanghoon , Lee Byung-Joo , Shin Sung-Chan , Cheon Yong-Il , Jo Hyunju , Lee Jin-Choon , Sung Eui-Suk , Lee Minhyung
Published: November 2022

Background and Objectives Parotid cancer is a rare malignancy tumor, constituting about 3% of head and neck cancers. Treatment of parotid carcinoma is challenging because of its rarity and unpredictable clinical course. Therefore, it is important to evaluate risk factors associated with prognosis and to predict adverse outcomes. In this article, we aimed to analyze risk factors associated with recurrence free survival in our 10-year single center retrospective study.Subjects and Method Retrospective medical chart review was performed for patients with parotid gland cancer who underwent parotidectomy with or without adjuvant treatment in our institute 2011 to 2020. Patient demographics, histopathologic results, operative method, treatment outcome were assessed.Results A total of 8 patients (15%) experienced recurrence. Old age and low body mass index was associated with recurrence. Univariate analysis also revealed that high clinical stage, tumor involvement in deep lobe and facial nerve, postoperative radiotherapy or concurrent chemo radiotherapy, positive resection margin, and high histologic grade were statistically significant with recurrence. Multivariate analysis concluded that facial nerve involvement with tumor was associated with higher incidence of recurrence. Deep lobe and facial nerve involvement, postoperative radiotherapy or concurrent chemo radiotherapy, positive resection margin, clinical stage, and histologic grade were statistically significant factors associated with recurrence free survival.Conclusion Our 10-year single institute study will be helpful for predicting adverse outcomes in parotid cancer patients.
Gut microbiota affects brain development and behavior
Authors: Kim Gun-Ha , Shim Jung-Ok
Published: November 2022

The gut covers a large surface area of the body and faces various external factors. The brain works in concert with commensal microbes in the gut to efficiently process the enormous amount of chemical signals that enter the gut every day. This review discusses: (1) evidence that gut bacteria can alter brain development and behavior, (2) mechanisms by which gut bacteria communicate with the brain, (3) preclinical and clinical studies demonstrating the impact of gut microbiota on autism spectrum disorder, and (4) variables worth consideration by future research on gut bacteria.
Is online objective structured clinical examination teaching an acceptable replacement in post-COVID-19 medical education in the United Kingdom?: a descriptive study
Authors: Motkur Vashist , Bharadwaj Aniket , Yogarajah Nimalesh
Published: November 2022

Purpose: Coronavirus disease 2019 (COVID-19) restrictions resulted in an increased emphasis on virtual communication in medical education. This study assessed the acceptability of virtual teaching in an online objective structured clinical examination (OSCE) series and its role in future education.Methods: Six surgical OSCE stations were designed, covering common surgical topics, with specific tasks testing data interpretation, clinical knowledge, and communication skills. These were delivered via Zoom to students who participated in student/patient/examiner role-play. Feedback was collected by asking students to compare online teaching with previous experiences of in-person teaching. Descriptive statistics were used for Likert response data, and thematic analysis for free-text items.Results: Sixty-two students provided feedback, with 81% of respondents finding online instructions preferable to paper equivalents. Furthermore, 65% and 68% found online teaching more efficient and accessible, respectively, than in-person teaching. Only 34% found communication with each other easier online; Forty percent preferred online OSCE teaching to in-person teaching. Students also expressed feedback in positive and negative free-text comments.Conclusion: The data suggested that generally students were unwilling for online teaching to completely replace in-person teaching. The success of online teaching was dependent on the clinical skill being addressed; some were less amenable to a virtual setting. However, online OSCE teaching could play a role alongside in-person teaching.
Efficacy analysis of targeted nanodrug for non-small cell lung cancer therapy
Authors: Li Tongtong , Zhou Tong , Liu Ying , Wang Jingyue , Yu Zhenxiang
Published: November 2022

Biological macromolecules have been widely used as biomedical carriers in treating non-small cell lung cancer (NSCLC) due to their biocompatibility, targeting, biodegradability, and antitumor efficacy. Nanotechnology has been used in clinics to treat many diseases, including cancer. Nanoparticles (NPs) can accumulate drugs into tumors because of their enhanced permeability and retention (EPR) effects. However, the lack of active targeting ligands affects NPs drug delivery. Arginine-glycine-aspartic (RGD), as a targeting ligand, has distinct advantages in targeting and safety. In the present study, an RGD peptide-modified nanogel called RGD−polyethylene glycol−poly (L-phenylalanine-co-L-cystine) (RGD−PEG−P (LP-co-LC−P (LP-co-LC) was investigated to deliver vincristine (VCR) as NSCLC therapy. The VCR-loaded targeted nanoparticle (RGD-NP/VCR) demonstrated excellent antitumor efficacy compared to the free drug (VCR) and untargeted nanoparticle (NP/VCR) without any significant side effects. RGD-NP/VCR has better tumor inhibition and fewer side effects, indicating its potential benefit in NSCLC treatment.
Theoretical analysis of the thermoelectric properties of penta-PdX2 (X = Se, Te) monolayer
Authors: Li Lei , Huang Zhuqin , Xu Jinqi , Huang Haihua
Published: November 2022

Based on the successful fabrication of PdSe2 monolayers, the electronic and thermoelectric properties of pentagonal PdX2 (X = Se, Te) monolayers were investigated via first-principles calculations and the Boltzmann transport theory. The results showed that the PdX2 monolayer exhibits an indirect bandgap at the Perdew–Burke–Ernzerhof level, as well as electronic and thermoelectric anisotropy in the transmission directions. In the PdTe2 monolayer, P-doping owing to weak electron–phonon coupling is the main reason for the excellent electronic properties of the material. The low phonon velocity and short phonon lifetime decreased the thermal conductivity (κl) of penta-PdTe2. In particular, the thermal conductivity of PdTe2 along the x and y transmission directions was 0.41 and 0.83 Wm−1K−1, respectively. Owing to the anisotropy of κl and electronic structures along the transmission direction of PdX2, an anisotropic thermoelectric quality factor ZT appeared in PdX2. The excellent electronic properties and low lattice thermal conductivity (κl) achieved a high ZT of the penta-PdTe2 monolayer, whereas the maximum ZT of the p- and n-type PdTe2 reached 6.6 and 4.4, respectively. Thus, the results indicate PdTe2 as a promising thermoelectric candidate.
Bioinformatic analysis identifies HPV-related tumor microenvironment remodeling prognostic biomarkers in head and neck squamous cell carcinoma
Authors: Zhou Qimin , Yuan Ouyang , Cui Hongtu , Hu Tao , Xiao Gary Guishan , Wei Jiao , Zhang Honglei , Wu Chengjun
Published: November 2022

Head and neck squamous cell carcinomas (HNSCCs) are highly aggressive tumors with rapid progression and poor prognosis. Human papillomavirus (HPV) infection has been identified as one of the most important carcinogens for HNSCC. As an early event in HNSCC, infection with HPV leads to altered immune profiles in the tumor microenvironment (TME). The TME plays a key role in the progression and transformation of HNSCC. However, the TME in HNSCC is a complex and heterogeneous mix of tumor cells, fibroblasts, different types of infiltrating immune cells, and extracellular matrix. Biomarkers relevant to the TME, and the biological role of these biomarkers, remain poorly understood. To this end, we performed comprehensive analysis of the RNA sequencing (RNA-Seq) data from tumor tissue of 502 patients with HNSCC and healthy tissue of 44 control samples. In total, we identified 4,237 differentially expressed genes, including 2,062 upregulated and 2,175 downregulated genes. Further in-depth bioinformatic analysis suggested 19 HNSCC tumor tissue-specific genes. In the subsequent analysis, we focused on the biomarker candidates shown to be significantly associated with unfavorable patient survival:ITGA5,PLAU,PLAUR,SERPINE1,TGFB1, andVEGFC. We found that the expression of these genes was negatively regulated by DNA methylation. Strikingly, all of these potential biomarkers are profoundly involved in the activation of the epithelial–mesenchymal transition (EMT) pathway in HNSCCs. In addition, these targets were found to be positively correlated with the immune invasion levels of CD4+T cells, macrophages, neutrophils, and dendritic cells, but negatively correlated with B-cell infiltration and CD8+T-cell invasion. Notably, our data showed that the expression levels ofITGA5,PLAU,PLAUR,SERPINE1, andTGFB1were significantly overexpressed in HPV-positive HNSCCs compared to normal controls, indicating the potential role of these biomarkers as transformation and/or malignant progression markers for HNSCCs in patients with HPV infection. Taken together, the results of our study proposeITGA5,PLAU,PLAUR,SERPINE1, andTGFB1as potential prognostic biomarkers for HNSCCs, which might be involved in the HPV-related TME remodeling of HNSCC. Our findings provide important implications for the development and/or improvement of patient stratification and customized immunotherapies in HNSCC.
Reconceptualize tall-cell variant papillary thyroid microcarcinoma: From a “sonographic histology” perspective
Authors: Zhang Yongyue , Mei Fang , He Xiaoxi , Ma Jing , Wang Shumin
Published: November 2022

Objective

This study aimed to examine the relationship between sonographic features and histological manifestations in the tall-cell variant of papillary thyroid microcarcinoma (TCV-PTMC), thus proposing the concept of “sonographic histology” and examine its value in the clinical management of the aggressive tall-cell variant.

Methods

This study retrospectively included 104 participants who were admitted to Peking University Third Hospital from 2015 to 2022 and were histopathologically confirmed as having TCV-PTMC or classical PTMC. We mainly compared the general characteristics, sonographic characteristics, and pathological specimens between the two cohorts.

Results

Hypoechoic nodules with a localized central isoechoic lesion and hypoechoic halo around nodules were most often observed in TCV-PTMC, which correlated with circumferentially distributed tumor epithelium and densely distributed tumor stroma histopathologically. Additionally, TCV-PTMC showed nodules with a more regular margin and less microcalcification than classical PTMC, which led to an underestimation of the risk of TCV-PTMC.

Conclusion

The good association between the ultrasound echo pattern and tissue cell arrangement was defined as sonographic histology in this study and can be applied in the preoperative identification of TCV-PTMC. This concept may provide novel insight for the identification of special subtypes of thyroid tumors and may modify pitfalls of the Thyroid Imaging Reporting and Data System in aggressive variants of microcarcinoma.
Optogenetic stimulation of Kiss1ARC terminals in the AVPV induces surge-like luteinizing hormone secretion via glutamate release in mice
Authors: Shen Xi , Liu Yali , Li Xiao Feng , Long Hui , Wang Li , Lyu Qifeng , Kuang Yanping , O’Byrne Kevin T.
Published: November 2022

Kisspeptin neurons are mainly located in the arcuate (Kiss1ARC, vis-à-vis the GnRH pulse generator) and anteroventral periventricular nucleus (Kiss1AVPV, vis-à-vis the GnRH surge generator). Kiss1ARC send fibre projections that connect with Kiss1AVPV somata. However, studies focused on the role of Kiss1ARC neurons in the LH surge are limited, and the role of Kiss1ARC projections to AVPV (Kiss1ARC→AVPV) in the preovulatory LH surge is still unknown. To investigate its function, this study used optogenetics to selectively stimulate Kiss1ARC→AVPV and measured changes in circulating LH levels. Kiss1ARC in Kiss-Cre-tdTomato mice were virally infected to express channelrhodopsin-2 proteins, and optical stimulation was applied selectively via a fibre optic cannula in the AVPV. Sustained 20 Hz optical stimulation of Kiss1ARC→AVPV from 15:30 to 16:30 h on proestrus effectively induced an immediate increase in LH reaching peak surge-like levels of around 8 ng/ml within 10 min, followed by a gradual decline to baseline over about 40 min. Stimulation at 10 Hz resulted in a non-significant increase in LH levels and 5 Hz stimulation had no effect in proestrous animals. The 20 Hz stimulation induced significantly higher circulating LH levels on proestrus compared with diestrus or estrus, which suggested that the effect of terminal stimulation is modulated by the sex steroid milieu. Additionally, intra-AVPV infusion of glutamate antagonists, AP5+CNQX, completely blocked the increase on LH levels induced by Kiss1ARC→AVPV terminal photostimulation in proestrous animals. These results demonstrate for the first time that optical stimulation of Kiss1ARC→AVPV induces an LH surge-like secretion via glutamatergic mechanisms. In conclusion, Kiss1ARC may participate in LH surge generation by glutamate release from terminal projections in the AVPV.
Masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism
Authors: Uchiyama-Matsuoka Natsumi , Tsuji Kenji , Uchida Haruhito A. , Kitamura Shinji , Itoh Yoshihiko , Nishiyama Yuki , Morimoto Eisaku , Fujisawa Satoshi , Terasaka Tomohiro , Hara Takayuki , Ogura-Ochi Kanako , Inagaki Kenichi , Wada Jun
Published: November 2022

Introduction

While it is well known that thyroid function may affect kidney function, the transition of the chronic kidney disease (CKD) status before and after treatment for thyroid disorders, as well as the factors affecting this change, remains to be explored. In the present study, we focused on the change in kidney function and their affecting factors during the treatment for both hyperthyroidism and hypothyroidism.

Methods

Eighty-eight patients with hyperthyroidism and fifty-two patients with hypothyroidism were enrolled in a retrospective and longitudinal case series to analyze the changes in kidney function and their affecting factors after treatment for thyroid disorders.

Results

Along with the improvement of thyroid function after treatment, there was a significant decrease in estimated glomerular filtration rate (eGFR) in hyperthyroidism (an average ΔeGFR of -41.1 mL/min/1.73 m2) and an increase in eGFR in hypothyroidism (an average ΔeGFR of 7.1 mL/min/1.73 m2). The multiple linear regression analysis revealed that sex, eGFR, free thyroxine (FT4) and free triiodothyronine (FT3) could be considered independent explanatory variables for ΔeGFR in hyperthyroidism, while age, eGFR, and FT3 were detected as independent explanatory variables in hypothyroidism. In addition, the stratification by kidney function at two points, pre- and post-treatment for thyroid disorders, revealed that 4.5% of the participants with hyperthyroidism were pre-defined as non-CKD and post-defined as CKD, indicating the presence of “masked” CKD in hyperthyroidism. On the other hand, 13.5% of the participants with hypothyroidism presented pre-defined CKD and post-defined non-CKD, indicating the presence of “reversible” CKD status in hypothyroidism.

Conclusions

We uncovered the population of masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism, thereby re-emphasizing the importance of a follow-up to examine kidney function after treatment for hyperthyroidism and the routine evaluation of thyroid function in CKD patients as well as the appropriate hormone therapy if the patient has hypothyroidism.
Suppression of endogenous retroviral enhancers in mouse embryos derived from somatic cell nuclear transfer
Authors: Shikata Daiki , Matoba Shogo , Hada Masashi , Sakashita Akihiko , Inoue Kimiko , Ogura Atsuo
Published: November 2022

Endogenous retroviruses (ERVs) in the mammalian genome play diverse roles in embryonic development. These developmentally related ERVs are generally repressed in somatic cells and therefore are likely repressed in embryos derived from somatic cell nuclear transfer (SCNT). In this study, we sought to identify ERVs that are repressed in SCNT-derived morulae, which might cause previously unexplained embryonic deaths shortly after implantation. Our transcriptome analysis revealed that, amongst ERV families, ERVK was specifically, and strongly downregulated in SCNT-derived embryos while other transposable elements including LINE and ERVL were unchanged. Among the subfamilies of ERVK, RLTR45-int was most repressed in SCNT-derived embryos despite its highest expression in control fertilized embryos. Interestingly, the nearby genes (within 5–50 kb, n = 18; 50–200 kb, n = 63) of the repressed RLTR45-int loci were also repressed in SCNT-derived embryos, with a significant correlation between them. Furthermore, lysine H3K27 acetylation was enriched around the RLTR45-int loci. These findings indicate that RLTR45-int elements function as enhancers of nearby genes. Indeed, deletion of two sequential RLTR45-int loci on chromosome 4 or 18 resulted in downregulations of nearby genes at the morula stage. We also found that RLTR45-int loci, especially SCNT-low, enhancer-like loci, were strongly enriched with H3K9me3, a repressive histone mark. Importantly, these H3K9me3-enriched regions were not activated by overexpression of H3K9me3 demethylase Kdm4d in SCNT-derived embryos, suggesting the presence of another epigenetic barrier repressing their expressions and enhancer activities in SCNT embryos. Thus, we identified ERVK subfamily RLTR45-int, putative enhancer elements, as a strong reprogramming barrier for SCNT (253 words).
Microglial cells: Sensors for neuronal activity and microbiota-derived molecules
Authors: D’Alessandro Giuseppina , Marrocco Francesco , Limatola Cristina
Published: November 2022

Microglial cells play pleiotropic homeostatic activities in the brain, during development and in adulthood. Microglia regulate synaptic activity and maturation, and continuously patrol brain parenchyma monitoring for and reacting to eventual alterations or damages. In the last two decades microglia were given a central role as an indicator to monitor the inflammatory state of brain parenchyma. However, the recent introduction of single cell scRNA analyses in several studies on the functional role of microglia, revealed a not-negligible spatio-temporal heterogeneity of microglial cell populations in the brain, both during healthy and in pathological conditions. Furthermore, the recent advances in the knowledge of the mechanisms involved in the modulation of cerebral activity induced by gut microbe-derived molecules open new perspectives for deciphering the role of microglial cells as possible mediators of these interactions. The aim of this review is to summarize the most recent studies correlating gut-derived molecules and vagal stimulation, as well as dysbiotic events, to alteration of brain functioning, and the contribution of microglial cells.
Oropharyngeal tumor cells induce COX-2 expression in peripheral blood monocytes by secretion of IL-1α
Authors: DeVoti James A. , Israr Mohd , Lam Fung , Papayannakos Christopher , Frank Douglas K. , Kamdar Dev P. , Pereira Lucio M. , Abramson Allan , Steinberg Bettie M. , Bonagura Vincent R.
Published: November 2022

Oropharyngeal squamous cell cancer (OPC) accounts for 3% of all cancers and greater than 1.5% of all cancer deaths in the United States, with marked treatment-associated morbidity in survivors. More than 80% of OPC is caused by HPV16. Tumors induced by HPV have been linked to impaired immune functions, with most studies focused on the local tumor microenvironment. Fewer studies have characterized the effects of these tumors on systemic responses in OPC, especially innate responses that drive subsequent adaptive responses, potentially creating feed-back loops favorable to the tumor. Here we report that elevated plasma levels of PGE2 are expressed in half of patients with OPC secondary to overexpression of COX-2 by peripheral blood monocytes, and this expression is driven by IL-1α secreted by the tumors. Monocytes from patients are much more sensitive to the stimulation than monocytes from controls, suggesting the possibility of enhanced immune-modulating feed-back loops. Furthermore, control monocytes pre-exposed to PGE2 overexpress COX-2 in response to IL-1α, simulating responses made by monocytes from some OPC patients. Disrupting the PGE2/IL-1α feed-back loop can have potential impact on targeted medical therapies.
A novel built-in adjuvant metallothionein-3 aids protein antigens to induce rapid, robust, and durable immune responses
Authors: Yin Ying , Gu Yanfei , Zai Xiaodong , Li Ruihua , Zhu Xinjie , Yu Rui , Zhang Jun , Wang Shuyi , Zhang Yue , Lin Jian , Xu Junjie , Chen Wei
Published: November 2022

Adjuvants are crucial components of vaccines that can enhance and modulate antigen-specific immune responses. Herein, we reported for the first time that human metallothionein-3 (MT3), a low molecular weight cysteine-rich metal-binding protein, was a novel promising adjuvant candidate that could help protein antigens to induce rapid, effective, and durable antigen-specific immune responses. In the present study, MT3 was fused to outer membrane protein 19 (Omp19) of Brucella abortus (MT3-Omp19, MO) and C fragment heavy chain (Hc) of tetanus neurotoxin (MT3-Hc, MH), respectively. The results showed that MT3 as a built-in adjuvant increased the Omp19- or Hc-specific antibody responses by 100-1000 folds in seven days after primary immunization. Compared to other commercially available adjuvants, MT3 could stimulate earlier (4 days after primary injection) and stronger (10-100 folds) antibody response with lower antigen dose, and its adjuvanticity relied on fusion to antigen. Although the mechanism was not clear yet, the fusion protein MO was observed to directly activate DCs, promote germinal center formation and improve the speed of Ig class switching. Interestingly, our subsequent study found that other members of the mammalian MT family (human MT1 or murine MT3 for examples) also had potential adjuvant effects, but their effects were lower than human MT3. Overall, this study explored a new function of human MT3 as a novel built-in adjuvant, which may have important clinical application potential in vaccine development against global pandemics.
ROS and DNA repair in spontaneous versus agonist-induced NETosis: Context matters
Authors: Azzouz Dhia , Palaniyar Nades
Published: November 2022

Reactive oxygen species (ROS) is essential for neutrophil extracellular trap formation (NETosis). Nevertheless, how ROS induces NETosis at baseline and during neutrophil activation is unknown. Although neutrophils carry DNA transcription, replication and repair machineries, their relevance in the short-lived mature neutrophils that carry pre-synthesized proteins has remained a mystery for decades. Our recent studies show that (i) NETosis-inducing agonists promote NETosis-specific kinase activation, genome-wide transcription that helps to decondense chromatin, and (ii) excess ROS produced by NADPH oxidase activating agonists generate genome-wide 8-oxy-guanine (8-OG), and the initial steps of DNA repair are needed to decondense chromatin in these cells. These steps require DNA repair proteins necessary for the assembly and nicking at the damaged DNA sites (poly ADP ribose polymerase PARP, apurinic endonuclease APE1 and DNA ligase), but not the enzymes that mediate the repair DNA synthesis (Proliferating cell nuclear antigen (PCNA) and DNA Polymerases). In this study, we show that (i) similar to agonist-induced NETosis, inhibition of early steps of oxidative DNA damage repair proteins suppresses spontaneous NETosis, but (ii) the inhibition of late stage repair proteins DNA polymerases and PCNA drastically promotes baseline NETosis. Hence, in the absence of excessive ROS generation and neutrophil activation, DNA repair mediated by PCNA and DNA polymerases is essential to prevent chromatin decondensation and spontaneous NETosis. These findings indicate that ROS, oxidative DNA damage, transcription and DNA repair differentially regulate spontaneous and agonist-induced NETosis. Therefore, context matters.