bluuebunny/crossref_metadata_2025 huggingface dataset:
A Rare Parathyroid Carcinoma in Young Adult Man: Therapeutic Challenges in Tertiary Hospital with its Limitations
Authors: Sitanggang Rupita Sari Endangena , Azhar Yohana , Agustina Hasrayati
Published: March 2024

Introduction: Parathyroid carcinoma is a rare malignant neoplasm. The symptoms that arise are related to hyperparathyroid conditions, which are clinically difficult to distinguish between benign and malignant disorders. These conditions make the diagnosis and treatment of parathyroid carcinoma challenging. Case Presentation: : In this case report, a 27-year-old male presented with weak limbs and a history of multiple recurrent fractures. Serum calcium ions and parathyroid hormone levels were increased. A comprehensive history taking, laboratory testing, and radiographic examination were used to confirm the diagnosis of parathyroid cancer. However, a histological study is still necessary to make a certain diagnosis. The patient underwent parathyroidectomy accompanied by intraoperative frozen section examination, then confirmed to have parathyroid carcinoma. Calcium serum evaluations were performed on the patient after surgery. Conclusions: Parathyroid carcinoma is a very rare case. Clinical manifestations and the results of investigations that are not typical and rarely found together in one patient’s condition make the diagnosis of this case very difficult. Although recommendations or standard protocols in the management of parathyroid carcinoma do not yet exist, the results of case reports are expected to increase the knowledge and management of parathyroid carcinoma patients.
THE EFFECT OF PROJECT-BASED LEARNING APPROACH ON STUDENTS’ ACADEMIC ACHIEVEMENT: A MIXED META-METHOD
Authors: Batdı Veli , Topkaya Yavuz , Jibril Shafiyu
Published: March 2024

The main purpose of this study is to investigate the effect of a project-based learning approach on students’ academic performance through a mixed meta-method. For this reason, a dual methodological approach meta-analytical of quantitative data and meta-thematic of qualitative data were used in determining the effect size in quantitative dimension, while, in the qualitative dimension the positive and negative aspects together with the recommendation was determined. To this end, meta-analysis was conducted using data from 26 studies and meta-thematic from 8 studies. In order to determine the effect size, CMA and MetaWin were used and the effect size was calculated at a large level with the value of g =.83 [-.02; 1.68], and a significant difference of p˂.05. In the meta-thematic analysis, the effect of project-based learning was found to have a positive effect as well as a little negative impact on students’ academic performance. Recommendations were also provided through the participants’ views. In both the meta-analysis and meta-thematic analysis, the findings showed that the project-based learning approach owns a great effect on the students’ academic performance.
LİSE ÖĞRENCİLERİNDE YAŞAM AMAÇLARI VE UMUDUN ÖZNEL İYİ OLUŞLA İLİŞKİSİNİN İNCELENMESİ
Authors: Deniz Elif , Ay İsmail
Published: March 2024

Öznel iyi oluş, kişinin yaşamdan aldığı doyumu ve yaşadığı olumlu duyguları ifade eden bir kavramdır. Yaşam amaçları, bireyin uzun vadede gerçekleştirmek istediği planlarıdır. Umut kişinin amaçlar ve bu amaçlara ulaşmak için yollar belirlemesi, ayrıca amaçlarına ulaşmak için motivasyona sahip olması durumudur. Bu çalışmada yaşam amaçları ve umudun öznel iyi oluşla ilişkisini incelemek amaçlanmıştır. Katılımcılar 2019-2020 eğitim yılında Muş ilindeki lise öğrencilerinden oluşmaktadır. Araştırmada ilişkisel tarama yöntemi kullanılmıştır. Verilerin analizinde gruplar arası (cinsiyet, yaşanılan yer, sınıf düzeyi, okul türü ve okul tercih sebebi) karşılaştırmalarda t-testi ve tek yönlü varyans analizi, değişkenler arasındaki ilişkiyi belirlemede pearson korelasyon analizi, yordama gücünün tespit edilmesi için çoklu regresyon analizi uygulanmıştır. Analiz sonuçları, yaşam amaçları ve umudun öznel iyi oluşla pozitif yönde ilişkili olduğunu göstermiştir. Ayrıca yaşam amaçları ve umudun öznel iyi oluşu manidar şekilde yordadığı sonucuna ulaşılmıştır. Gelecek araştırmalarda deneysel metodlar kullanılabilir ve çalışma farklı yaş gruplarında tekrarlanabilir. Okuldaki rehberlik çalışmalarında umut ve yaşam amaçlarına yer verilerek öznel iyi oluşa katkıda bulunulabilir.
Utilization of Plants as Traditional Medicine by the People of Momiwaren Village, West Papua
Authors: Siburian Rima Herlina , Angrianto Rusdy
Published: March 2024

Momiwaren Village is one of the villages close to the Momiwaren Protected Forest Area. In line with regional development and technological advances, knowledge of the use of plants as medicinal ingredients is starting to disappear. For this reason, it is necessary to conduct research on how many types of plants are still used by the community as medicinal ingredients. The method used in this research is a survey method with interview techniques. The results of this research show that the people of Momiwaren Village still use plants as medicinal ingredients. There are 30 species from 22 families used by the community. If we look at the conservation status of the plants used, the types of plants used are still included in the naturally available (LC/DD) category, but there is one type of plant that is threatened with extinction and requires further silvicultural action so that this plant can be cultivated and not extinct from nature.
Navigating Vascular Complexity
Authors:   , Meijer Elana Marianne
Published: March 2024

The research collected in this thesis focusses on the vascular system, emphasizing its heterogeneity and complexity in both health and disease. It argues for tailored approaches in vascular replacement, pre-vascularization strategies, and disease modeling.

The first part centers on the use of human induced pluripotent stem cell (hiPSC)-derived vascular cells for tissue engineering and disease modeling. The main cell source used in this thesis are cells derived from hiPSC-derived blood vessel organoids. We hypothesized that vascular organoid derived cells would be a suitable cell source for the development of various vascular (disease) models.

With multiple advanced in vitro techniques, we confirmed that these cells offer a versatile platform for both micro- and macrovascular regeneration. The chapters in this thesis dissect various aspects using vascular organoid derived cells. For example we induced and regulated fenestrations in hiPSC-derived endothelial cells and we compared the phenotypic switch in hiPSC-derived vascular smooth muscle cells to their natural counterparts. In parallel, the thesis explores the impact of mechanical stimuli in advanced 3D models, aiming to replicate physiological conditions accurately.

The thesis also investigates the impact of mechanical forces in vascular regulation and disease modeling. We introduce innovative approaches like a microfluidic chip to study vascular pathologies in vitro, particularly focusing on early-stage atherosclerosis. This model offers insights into vascular cell interactions under physiologically relevant conditions, a potential platform for drug testing and mechanistic studies.

Throughout this thesis, there's an aim towards animal-free alternatives for culture components, mainly including Matrigel, aligning with ethical and translational research goals. The ultimate aim is to bridge the gap between bench and bedside, leveraging hiPSC-derived cells for personalized regenerative therapies and disease interventions.

The studies in this thesis contain hiPSCs from healthy donors. Future prospects include the use of patient-derived cells, to be able to study vascular development in disease conditions. In addition, using patient-derived cells would open up the possibilities for the development of drug-screening platforms and individualized disease models.

In conclusion, the thesis underscores the potential of hiPSC-derived vascular cells in reshaping the landscape of vascular regeneration and disease modeling. It not only advances our understanding of vascular biology but also paves the way for innovative solutions in clinical practice, a step towards personalized medicine.
Pengelolaan kelas untuk meningkatkan prestasi belajar matematika siswa dengan menggunakan strategi pembelajaran aktif tipe Hollywood Squares Review pada kelas VIII SMP Negeri 2 Na. IX-X
Authors: Fauzy Ariska Septieny , Siregar Sakinah Ubudiyah , Julyanti Eva
Published: March 2024

Penelitian ini bertujuan untuk meningkatkan prestasi belajar matematika siswa dengan menggunakan strategi pembelajaran aktif tipe Hollywood Squares Review di kelas VIII SMP Negeri 2 Na. IX-X. Desain eksperimental dengan pendekatan pretest-posttest digunakan pada penelitian ini. Sampel penelitian terdiri dari siswa kelas VIII-1 sebagai kelas eksperimental dan siswa kelas VIII-2 sebagai kelas kontrol, yang diambil secara random setelah dilaksanakan uji homogenitas dan normalitas. Dalam proses pembelajaran, kelas kontrol maupun kelas eksperimen mengaplikasikan pendekatan saintifik berdasarkan kurikulum 2013, strategi pembelajaran Hollywood Squares Review diterapkan pada kelas eksperimen, sedangkan kelas kontrol tidak diberikan perlakuan. Analisis data dilakukan dengan menggunakan uji t. Nilai signifikansi 0.000 < 0.05 ditemukan dalam hasil tes analisis data, yang menunjukkan bahwa menggunakan teknik pembelajaran Hollywood Squares Review dapat meningkatkan prestasi belajar.
PENGARUH EARNING PER SHARE DAN PRICE TO BOOK VALUE TERHADAP HARGA SAHAM PADA PERUSAHAAN SUBSEKTOR PERBANKAN YANG TERDAFTAR DI BEI TAHUN 2018-2019
Authors: Novia Sandra Dewi  , Sri Wahyuni  , Nurwahyuni Syahrir
Published: March 2024

Tujuan penelitian adalah untuk mengetahui pengaruh earning per share dan price to book value terhadap harga saham pada perusahaan subsektor perbankan yang terdaftar di BEI tahun 2018-2019. Penelitian ini bermanfaat bagi investor maupun calon investor dalam mengambil keputusan bisnis yang berkaitan dengan pengaruh EPS dan PBV terhadap harga saham. Penelitian ini menggunakan metode penelitian deskriptif kuantitatif dengan data sampel sebanyak 40 perusahaan perbankan yang terdaftar di BEI. Teknik analisis data yang digunakan adalah uji asumsi klasik, analisis regresi linear berganda, dan uji hipotesis. Hasil penelitian secara parsial menunjukan bahwa earning per share berpengaruh positif signifikan terhadap harga saham dengan thitung 5.15>ttabel 1.99 dan signifikansi 0.000<0.05. Price to book value berpengaruh positif signifikan terhadap harga saham dengan thitung 3.09>ttabel 1.99 dan signifikansi 0.0003<0.05. Adapun hasil uji secara simultan menunjukkan bahwa earning per share dan price to book value berpengaruh positif signifikan terhadap harga saham dengan nilai Fhitung 22.893>Ftabel 3.11 dan tingkat signifikansi 0.000<0.005. Saran dari penelitian ini adalah perusahaan diharapkan dapat mempertahankan bahkan mampu meningkatkan laba yang diperoleh, manajemen harus mempertimbangkan pembagian dividen bagi para pemegang saham karena memberikan daya tarik bagi para investor dalam membeli saham.
STRATEGI PEMASARAN DALAM MENINGKATKAN NASABAH PADA ASURANSI SYARIAH PT ASURANSI JIWA SAYRIAH AL AMIN KEDRI
Authors: Madyasari Arlupi Yulia , Andriani
Published: March 2024

Perusahaan asuransi merupakan organisasi non bank yang memegang peranan sangat penting, tidak jauh berbeda dengan bank yang memberikan pelayanan kepada nasabah masyarakat untuk menghadapi risiko yang akan datang. Secara umum, konsep asuransi adalah suatu ketentuan yang dilakukan oleh sekelompok individu yang dihadapkan pada kerugian yang tidak terduga. Semua perusahaan asuransi berlomba-lomba meningkatkan strategi pemasaran produknya untuk menarik konsumen dan pemegang polis. Strategi pemasaran merupakan suatu bentuk perencanaan suatu usaha untuk mencapai tujuannya dengan hasil yang optimal. Dalam dunia perasuransian, persaingan merupakan hal yang perlu diperhatikan, khususnya dalam bidang pemasaran, pemasaran merupakan faktor terpenting yang sangat mempengaruhi kinerja suatu lembaga asuransi. lembaga asuransi harus mengadakan komunikasi promosi kepada calon nasabah, karena ini merupakan kunci sukses dalam memberikan produk atau jasa kepada calon nasabah. Strategi pemasaran yang diterapkan oleh PT Asuransi Jiwa Syariah Kediri adalah strategi bauran pemasaran yang terdiri dari strategi produk, strategi harga, strategi lokalisasi, strategi promosi, strategi pelayanan dan strategi bauran lainnya.
DETERMINAN AUDIT DELAY DAN PENGARUHNYA TERHADAP REAKSI INVESTOR
Authors: Moch Sulthoni
Published: March 2024

Audit delay can be occur in all corporation. Audit delay refers to the length as needed by auditor for company audited from the auditee’s fiscal year-end to the audit report date. On time information will be quick reaction by investor.

This reseach divided two model. First model aim to identification and examine what are company size, industry type, financial perfomance, auditor opinion, type of audit firm, and debt ratio. Second model is examine audit delay associated with investor reaction. This reseach use to purposive sampling. Total elected sampling is 486 company 2007-2008. This reseach use to multiple regression.

The result first model reseach indicate that from six audit delay variable, three variable influence with audit delay are industry type, financial performance, and type of audit firm. Other variable not influence with audit delay are company size, opinion auditor, and debt ratio. The result second model reseach indicate that audit delay  associated with investor reaction proxied by abnormal return and volume trading activity.
ANALISIS PENGARUH VARIABEL PERATAAN LABA TERHADAP EKSPEKTASI KINERJA LABA MASA DEPAN PERUSAHAAN MANUFAKTUR DI BURSA EFEK INDONESIA TAHUN 2007-2008
Authors: RITA PUSPITASARI
Published: March 2024

Informasi laba merupakan komponen laporan keuangan perusahaan yang bertujuan untuk menilai kinerja manajemen, membantu  mengestimasi kemampuan  laba yang representatif dalam jangka panjang, meramalkan laba, menaksir resiko dalam berinvestasi. Hal ini disadari oleh manejem perusahaan, sehingga cenderung melakukan perilaku tak semestinya yaitu dengan melakukan praktik perataan laba. Dalam hal ini perusahaan manufaktur yang  dijadikan sorotan, karena perusahaan  manufaktur sebagai emiten terbesar dari seluruh perusahaan yang go public di Bursa Efek  Indonesia tentunya tidak bisa lepas dari praktik perataan laba. Penelitian ini bertujuan untuk membuktikan bahwa ada hubungan yang signifikan antara faktor perataan laba seperti laba bersih, leverage, total asset, ukuran perusahaan, dan  discretionary accrual  terhadap kinerja (laba) masa depan perusahaan.

Penelitian ini merupakan penelitian yang bersifat korelatif, yaitu mencari hubungan antara perataan laba (income  smoothing) dengan ekspektasi kinerja (laba) masa depan. Sampel dalam penelitian ini adalah  122  perusahaan manufaktur  yang  terdaftar di Bursa Efek Indonesia selama tahun 2007 sampai dengan 2008. Variabel dalam penelitian ini adalah variabel independen yang meliputi: net earning, leverage, total asset, size, discretionary accrual dan expected earning sebagai variabel dependen. Metode pengumpulan data dalam penelitian  ini adalah metode dokumentasi yang diambil dari  laporan keuangan perusahaan terkait dan buku-buku yang menunjang dalam penelitian. Analisis data untuk penelitian ini adalah dengan analis uji asumsi klasik, uji korelasi, uji determinasi (r²), uji F dan uji individual (uji t) .

Hasil penelitian ini menyatakan bahwa variabel perataan laba (net earning,  leverage, total asset, size, dan discretionary accrual) mempunyai pengaruh signifikan terhadap kinerja (laba) masa depan perusahaan manufaktur yang go public di  Bursa  Efek  Indonesia. Hal ini di buktikan dengan hasil Uji Keberartian Model (Uji F) yakni variabel independen besama-sama berpengaruh secara signifikan terhadap expected  earning, dan juga dibuktikan dengan hasil  uji  koefisien determinasi (r²) yang nilainya  cukup tinggi sebesar 97,7% sehingga dapat disimpulkan bahwa ada hubungan yang signifikan antara perataan laba dengan expected earning perusahaan. Namun ada variabel perataan laba yang dinyatakan tidak berpengaruh secara signifikan terhadap ekspektasi kinerja (laba) masa depan perusahaan pada Uji Signifikansi Parameter Individual. Analisis regresi dengan menggunakan metode uji-t dengan taraf signifikansi 0,05 menunjukkan bahwa dari lima variabel yang diujikan terhadap expected earning, hanya dua variabel yang memiliki pengaruh  signifikanyakni net earnings dan total asset perusahaan.
PENGARUH VARIABEL SUMBER DANA PERUSAHAAN TERHADAP RENTABILITAS MODAL SENDIRI (Studi Pada Perusahaan Makanan dan Minuman yang Terdaftar di Bursa Efek Indonesia)
Authors: Wiwiek Kusumaning Asmoro
Published: March 2024

This study aimed in determining influence of company’s funds sources on Return on

Equity (ROE) for foods and beverages companies listed their shares in Indonesian Stock Exchange

(IDX), based on their financial statements from the year 2007 until 2010

Variables used in this study comprises dependent variable, namely Return on Equity

(ROE) and independent variables, i.e. intern and extern funds. Intern funds comprise Flowback

Ratio while intern funds comprises The Debt to Total Capitalazition, Total Debt to Total Assets

and Debt to Equity. Multiple linier regression with probability rate 0,05 indicated that: In first

analysis (2007-2008), extern funds i.e. The Debt to Total Capitalazition, Total Debt to Total Assets,

Debt to Equity and intern fund namely Flowback Ratio simultaneously had no significance

influence on Return on Equity (ROE), it was proved by F calculate = -0,164 with significance rate

0,955 while in second analysis (2009-2010) all of independent variable i.e. intern and extern fund

simultaneously had significant influence on Return on Equity (ROE) it was proved by F calculate

= 20.701 with signification rate 0,000. Debt to Equity was independent variable which had

dominant influence on Return on Equity (ROE) with significance rate 0,000 and t calculate = -

8.667.

Conclusion, when economy’s condition was stable (2007-2008), the bigger company’s

long term debt and retained earning would result the higher company’s Return on Equity. But

when economy’s condition wasn’t stable (2009-2010) bigger long term debt would not rise Return

on Equity while bigger retained earning would rise Returnd on Equity.
ANALISIS RASIO KEUANGAN UNTUK MENILAI PERTUMBUHAN PERUSAHAAN (pada perusahaan PT. Gudang Garam Tbk. Kediri)
Authors: Hendra kusuma
Published: March 2024

The successof a companyin its effortsto bemore easilymeasured throughfinancial ratio analysis.Withfinancial ratio analysiswill be knownthe growth ofthe company.The financialhealthof a companyis one manifestationofthe company's overallperformanceshould beaddressed seriouslybythe company.Becauseahealthy companyin thefinancial, the company's growthcan be seenclearly. Todetermine the extent ofthe growthof a company, it can be preparedfinancial statementsincludethe balance sheetand profit andlossshouldbeaccounted fortruthand supportedbygood financialratio calculation.
FAKTOR - FAKTOR YANG MEMPENGARUHI KEPATUHAN WAJIB PAJAK DALAM MELAPORKAN SURAT PEMBERITAHUAN TAHUNAN (SPT)
Authors: Hijrah Safitri
Published: March 2024

Penelitian ini bertujuan untuk mengetahui faktor-faktor yang mempengaruhi kepatuhan Wajib Pajak dalam melaporkan Surat Pemberitahuan Tahunan (SPT) di Kediri. Variabel yang digunakan dalam penelitian ini adalah variabel dependen yaitu kepatuhan Wajib Pajak dalam melaporkan SPT, sedangkan variabel independennya yaitu kesadaran Wajib Pajak, pelayanan fiskus, sanksi pajak, dan persepsi atas efektifitas sistem perpajakan.

Data yang digunakan dalam penelitian ini adalah data primer dengan menggunakan kuesioner. Sampelnya adalah Wajib Pajak Orang Pribadi yang memilik NPWP di Kediri. Metode pengumpulan sampel ini adalah sampel acak sederhana. Teknik analisis data yang digunakan dalam penelitian ini adalah teknik analisis regresi berganda.

Berdasarkan hasil analisis yang dilakukan maka diperoleh kesimpulan bahwa kesadaran wajib pajak berpengaruh signifikan terhadap kepatuhan wajib pajak dalam melaporkan SPT, sedangkan pelayanan fiskus, sanksi pajak, dan persepsi efektifitas berpengaruh tetapi tidak signifikan terhadap kepatuhan wajib pajak dalam melaporkan SPT.
ANALISIS PENERAPAN PENYUSUNAN LAPORAN KEUANGAN UMKM BERDASARKAN SAK ETAP
Authors: Agus Andriyani Purnani Sari
Published: March 2024

The financial statement is the primary means of communicating financial information to parties outside of the company, which contains the results of the accounting process that can be used as a means of communication between financial information and or activity of a company with the parties concerned with the information or corporate activity, In this case UD. Irawan Jaya Plastindo as entity that publishes general purpose financial statement for external users is expected to make a financial report in accordance with the standard, it is the standards of financial accounting entity without public accountability (SFA EWPA) standard reserved for SMEs.

The purpose of this study is to investigate the compilation and presentation of financial statement by an entity's financial accounting standards without public accountability (SFA EWPA), This research uses descriptive quantitative research with the case study method. The results of this study indicate that UD. Irawan Jaya Plastindo SFA EWPA not apply in preparing its financial statements, it is due to limited knowledge possessed by the company and its human resources.
De Sementes a Jardins: Transcrição e Orquestração em “Notations VII” de Pierre Boulez
Authors: Leão Maia Igor , Mendes Vasconcelos Felipe , Araújo Alves Samuel
Published: March 2024

Este artigo analisa a transcrição realizada por Pierre Boulez do sétimo movimento das Douze Notations para piano, resultando na peça Notations VII para orquestra. Nosso objetivo é compreender as técnicas composicionais utilizadas, abordando aspectos estruturais, temporais, harmônicos e timbrísticos. Dividido em cinco partes, o texto inicia com uma introdução às Douze Notations e as transcrições feitas por Boulez, embasada em seus próprios escritos. Em seguida, apresentamos uma análise da miniatura para piano, seguida de uma contextualização do termo “proliferação” e de uma análise da versão orquestral. A reflexão final destaca os tipos de proliferação realizados por Boulez, as quais denominamos como proliferação temporal-estrutural, proliferação temporal-heterofônica e proliferação harmônico-tímbrica.
Andragogy in Practice: Applying a Theoretical Framework to Team Science Training in Biomedical Research
Authors: Knapke Jacqueline M. , Hildreth Laura , Molano Jennifer R. , Schuckman Stephanie M. , Blackard Jason T. , Johnstone Megan , Kopras Elizabeth J. , Lamkin M. K. , Lee Rebecca C. , Kues John R. , Mendell Angela
Published: March 2024

This study is the first to apply the theoretical principles of Malcolm Knowles’ theory of andragogy to evaluate data collected from learners who participated in team science training workshops in a biomedical research setting. Briefly, andragogy includes six principles: the learner’s self-concept, the role of experience, readiness to learn, orientation to learning, the learner’s need to know, and intrinsic motivation. Using an embedded study design, the primary focus was on qualitative data, with quantitative data complementing the qualitative findings. The deductive analysis demonstrated that approximately 85% of the qualitative data could be connected to at least one andragogical principle. Participant responses to positive evaluation questions were largely related to two principles: readiness to learn and problem-based learning orientation. Participant responses to negative questions were largely connected to two different principles: the role of experience and self-direction. Inductive analysis found an additional theme: meeting biological needs. Quantitative survey results supported the qualitative findings. The study findings demonstrate that andragogy can serve as a valuable construct to integrate into the development of effective team science training for biomedical researchers.
Codon-optimization in gene therapy: promises, prospects and challenges
Authors: Paremskaia Anastasiia Iu , Kogan Anna A. , Murashkina Anastasiia , Naumova Daria A. , Satish Anakha , Abramov Ivan S. , Feoktistova Sofya G. , Mityaeva Olga N. , Deviatkin Andrei A. , Volchkov Pavel Yu
Published: March 2024

Codon optimization has evolved to enhance protein expression efficiency by exploiting the genetic code’s redundancy, allowing for multiple codon options for a single amino acid. Initially observed in E. coli, optimal codon usage correlates with high gene expression, which has propelled applications expanding from basic research to biopharmaceuticals and vaccine development. The method is especially valuable for adjusting immune responses in gene therapies and has the potenial to create tissue-specific therapies. However, challenges persist, such as the risk of unintended effects on protein function and the complexity of evaluating optimization effectiveness. Despite these issues, codon optimization is crucial in advancing gene therapeutics. This study provides a comprehensive review of the current metrics for codon-optimization, and its practical usage in research and clinical applications, in the context of gene therapy.
Transmissibility of Mycobacterium pinnipedii in a murine model
Authors: Marfil María Jimena , Blanco Federico Carlos , Colombatti Olivieri María Alejandra , Eirin María Emilia , Zumárraga Martín José
Published: March 2024

The causative agent of tuberculosis in pinnipeds is Mycobacterium pinnipedii, a member of the Mycobacterium tuberculosis complex (MTC). The natural hosts are pinnipeds; however, other non-marine mammals, including humans, can also be infected. The transmissibility of a pathogen is related to its virulence. The transmissibility of a M. pinnipedii strain (i.e., 1856) was investigated in a murine model and compared with that of two Mycobacterium bovis strains (i.e., 534 and 04-303) with different reported virulence. Non-inoculated mice (sentinels) were co-housed with intratracheally inoculated mice. Detailed inspection of mice to search for visible tuberculosis lesions in the lungs and spleen was performed, and bacillus viability at 30, 60, and 90 days post-inoculation (dpi) was assayed. A transmissibility of 100% was recorded at 30 dpi in sentinel mice co-housed with the inoculated mice from the M. pinnipedii and M. bovis 04-303 groups, as evidenced by the recovery of viable M. pinnipedii and M. bovis from the lungs of sentinel mice. Mice inoculated with M. pinnipedii (1856) and M. bovis (534) survived until euthanized, whereas five of the M. bovis 04-303-inoculated mice died at 17 dpi. This study constitutes the first report of the transmissibility of a M. pinnipedii strain in mice and confirms the utility of this experimental model to study virulence features such as the transmission of poorly characterized MTC species.
Determining complex petroleum migration pathways along faults and sandbodies: a new method and application
Authors: Jijian Shi , Guang Fu , Lili Li
Published: March 2024

Introduction: The reservoir-forming rule in the paleo-slope zone outside petroliferous basins’ source kitchens of the eastern basin in China is unclear, manifested in the distribution of oil and gas in complex multi-layers. This study focuses on petroleum migration along faults and sandbodies to clarify this question and improve the exploration efficiency of petroleum in areas with similar geological conditions.

Method: We summarized two models of petroleum migration based on two factors: the connected sandbodies and the vertical unsealing faults. Model I is conducive to the migration of hydrocarbons within a single layer, while Model II is conducive to the vertical migration of hydrocarbons across layers. Combining the means for evaluating fault sealing and sandbody connectivity, integrating these models could form a set of characterization methods for the distribution of the complex fluid migration pathways.

Results: This method is applied to characterize the complex multilayer migration pathways distribution in the first and second members of the Shahejie Formation in the central-southern area of the Wen’an Slope in the Baxian Sag, Jizhong Depression, Bohai Bay Basin, China. The results show that, in the first and second members of the Shahejie Formation in the central-southern area of the Wen’an Slope, the area for Model II is mainly distributed in the central-eastern regions. The second member has a Model I area distributed in its western region, and the first member has a Model I area distributed in its centraleastern parts. The latter distribution area is larger than the former. According to hydrocarbon migration analysis, the first member is more conducive to large regional migration and accumulation of hydrocarbons than the second member.

Discussion: The predicted result of petroleum migration is consistent with the hydrocarbon distribution found in the central-southern areas of the Wen’an Slope, which is that oil and gas distribution in the first member is significantly greater than that in the second member. Thus, our method is feasible for characterizing the regional distribution of complex multi-layer migration pathways in simple tectonic setting and oil source conditions. However, further research is still needed to increase the effectiveness of present petroleum migration analysis.
Role of CRH in colitis and colitis-associated cancer: a combinative result of central and peripheral effects?
Authors: Zhu Chao , Li Shengnan
Published: March 2024

Corticotropin-releasing factor family peptides (CRF peptides) comprise corticotropin releasing hormone (CRH), urocortin (UCN1), UCN2 and UCN3. CRH is first isolated in the brain and later with UCNs found in many peripheral cells/tissues including the colon. CRH and UCNs function via the two types of receptors, CRF1 and CRF2, with CRH mainly acting on CRF1, UCN1 on both CRF1 &CRF2 and UCN2-3 on CRF2. Compiling evidence shows that CRH participates in inflammation and cancers via both indirect central effects related to stress response and direct peripheral influence. CRH, as a stress-response mediator, plays a significant central role in promoting the development of colitis involving colon motility, immunity and gut flora, while a few anti-colitis results of central CRH are also reported. Moreover, CRH is found to directly influence the motility and immune/inflammatory cells in the colon. Likewise, CRH is believed to be greatly related to tumorigenesis of many kinds of cancers including colon cancer via the central action during chronic stress while the peripheral effects on colitis-associated-colon cancer (CAC) are also proved. We and others observe that CRH/CRF1 plays a significant peripheral role in the development of colitis and CAC in that CRF1 deficiency dramatically suppresses the colon inflammation and CAC. However, up to date, there still exist not many relevant experimental data on this topic, and there seems to be no absolute clearcut between the central and direct peripheral effects of CRH in colitis and colon cancer. Taken together, CRH, as a critical factor in stress and immunity, may participate in colitis and CAC as a centrally active molecule; meanwhile, CRH has direct peripheral effects regulating the development of colitis and CAC, both of which will be summarized in this review.
Design and optimization analysis of a new double-layer tube type heat exchanger for lead-bismuth reactors
Authors: Qi JingWen , Ai QingSong , Zhao PengCheng , Yang Junkang , Wang GuiMei
Published: March 2024

Double-layer heat tubes have been designed to effectively reduce the occurrence of heat pipe rupture accidents. However, inter-tube thermal contact resistance can decrease heat transfer efficiency, thus hampering the heat dissipation in the primary loop system of lead-bismuth reactors. Therefore, optimizing the design of double-layer heat tubes is necessary. This work focuses on the double-layer heat exchanger of a lead-bismuth reactor and utilizes gallium-based graphene nanofluids as a thermal interface material to fill the gap between the heat tubes. Furthermore, the impact of the length, wall thickness, outer diameter, and spacing of heat tubes on the heat transfer performance of the double-layer heat exchanger with and without the nanofluids has been analyzed. The study aims to optimize the JF factor and cost-effectiveness ratio (CER). Genetic algorithms are employed to optimize and evaluate the heat transfer performance of the main heat exchanger based on the four aforementioned parameters. Consequently, a new design scheme is obtained for the double-layer heat exchanger, which increases the optimized overall heat transfer coefficient of the main heat exchanger by 5.79%, pressure drop in the primary loop by 2.32%, JF factor by 5%, and CER by 24.62%. These results demonstrate that the gallium-based graphene nanofluids can effectively enhance the heat transfer performance of the double-layer heat exchanger while reducing the likelihood of steam generator tube rupture accidents.
Two-stage collaborative information interaction reliability improvement for the distribution grid
Authors: Shi Zhan
Published: March 2024

The impulse noise generated by a large volume of power electronics devices imposes a hazardous impact on information interaction reliability in low-voltage distribution grids. In this paper, we propose a two-stage collaborative information interaction reliability improvement algorithm to minimize the bit error rate (BER) of the information interaction under impulse noise. In the first stage, the transmission-side peak-to-average power ratio (PAPR) is reduced based on the adaptive particle swarm optimization (PSO)-enabled partial transmit sequence (PTS). In the second stage, the reception-side dual-signal blanking is proposed based on the transmission-side PAPR and reception-side useful signal power estimation and peak median ratio. The transmission–reception collaborative information interaction reliability improvement is realized through two aspects. First, transmission-side PAPR reduction improves the performance of reception-side signal blanking by making it easier to distinguish useful signals from impulse noise. Second, the transmission-side PAPR is utilized to improve the estimation accuracy of both coarse and precise thresholds in dual-signal blanking. Simulation results show that the proposed algorithm outperforms existing algorithms in both PAPR reduction and BER performances to achieve information interaction reliability improvement effectively.
Co-formulation of the rF1V plague vaccine with depot-formulated cytokines enhances immunogenicity and efficacy to elicit protective responses against aerosol challenge in mice
Authors: Galloway Darrell R. , Li Jiahui , Nguyen Nguyen X. , Falkenberg Frank W. , Henning Lisa , Krile Robert , Chou Ying-Liang , Herron James N. , Hale J. Scott , Williamson E. Diane
Published: March 2024

This study evaluated a depot-formulated cytokine-based adjuvant to improve the efficacy of the recombinant F1V (rF1V) plague vaccine and examined the protective response following aerosol challenge in a murine model. The results of this study showed that co-formulation of the Alhydrogel-adsorbed rF1V plague fusion vaccine with the depot-formulated cytokines recombinant human interleukin 2 (rhuIL-2) and/or recombinant murine granulocyte macrophage colony-stimulating factor (rmGM-CSF) significantly enhances immunogenicity and significant protection at lower antigen doses against a lethal aerosol challenge. These results provide additional support for the co-application of the depot-formulated IL-2 and/or GM-CSF cytokines to enhance vaccine efficacy.
Bioinformatic validation and machine learning-based exploration of purine metabolism-related gene signatures in the context of immunotherapeutic strategies for nonspecific orbital inflammation
Authors: Wu Zixuan , Fang Chi , Hu Yi , Peng Xin , Zhang Zheyuan , Yao Xiaolei , Peng Qinghua
Published: March 2024

Background

Nonspecific orbital inflammation (NSOI) represents a perplexing and persistent proliferative inflammatory disorder of idiopathic nature, characterized by a heterogeneous lymphoid infiltration within the orbital region. This condition, marked by the aberrant metabolic activities of its cellular constituents, starkly contrasts with the metabolic equilibrium found in healthy cells. Among the myriad pathways integral to cellular metabolism, purine metabolism emerges as a critical player, providing the building blocks for nucleic acid synthesis, such as DNA and RNA. Despite its significance, the contribution of Purine Metabolism Genes (PMGs) to the pathophysiological landscape of NSOI remains a mystery, highlighting a critical gap in our understanding of the disease’s molecular underpinnings.

Methods

To bridge this knowledge gap, our study embarked on an exploratory journey to identify and validate PMGs implicated in NSOI, employing a comprehensive bioinformatics strategy. By intersecting differential gene expression analyses with a curated list of 92 known PMGs, we aimed to pinpoint those with potential roles in NSOI. Advanced methodologies, including Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA), facilitated a deep dive into the biological functions and pathways associated with these PMGs. Further refinement through Lasso regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) enabled the identification of key hub genes and the evaluation of their diagnostic prowess for NSOI. Additionally, the relationship between these hub PMGs and relevant clinical parameters was thoroughly investigated. To corroborate our findings, we analyzed expression data from datasets GSE58331 and GSE105149, focusing on the seven PMGs identified as potentially crucial to NSOI pathology.

Results

Our investigation unveiled seven PMGs (ENTPD1, POLR2K, NPR2, PDE6D, PDE6H, PDE4B, and ALLC) as intimately connected to NSOI. Functional analyses shed light on their involvement in processes such as peroxisome targeting sequence binding, seminiferous tubule development, and ciliary transition zone organization. Importantly, the diagnostic capabilities of these PMGs demonstrated promising efficacy in distinguishing NSOI from non-affected states.

Conclusions

Through rigorous bioinformatics analyses, this study unveils seven PMGs as novel biomarker candidates for NSOI, elucidating their potential roles in the disease’s pathogenesis. These discoveries not only enhance our understanding of NSOI at the molecular level but also pave the way for innovative approaches to monitor and study its progression, offering a beacon of hope for individuals afflicted by this enigmatic condition.
The expression of CTLA-4 in hepatic alveolar echinococcosis patients and blocking CTLA-4 to reverse T cell exhaustion in Echinococcus multilocularis-infected mice
Authors: Yang Yuxuan , Wuren Tana , Wu Binjie , Cheng Shilei , Fan Haining
Published: March 2024

Alveolar echinococcosis (AE) is a zoonotic parasitic disease caused by the infection of Echinococcus multilocularis (E. multilocularis) larvae. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) produces inhibitory signals and induces T cell exhaustion, thereby inhibiting the parasiticidal efficacy of the liver immune system. Therefore, the purpose of this study is to explore how T-cell exhaustion contributes to AE and whether blocking CTLA-4 could reverse T cell exhaustion. Here we discovered that the expression of CTLA-4 was increased in the infiltrating margin around the lesion of the liver from AE patients by using western blot and immunohistochemistry assay. Multiple fluorescence immunohistochemistry identified that CTLA-4 and CD4/CD8 molecules were co-localized. For in vitro experiments, it was found that the sustained stimulation of E. multilocularis antigen could induce T cell exhaustion, blocking CTLA-4-reversed T cell exhaustion. For in vivo experiments, the expression of CTLA-4 was increased in the liver of E. multilocularis-infected mice, and the CTLA-4 and CD4/CD8 molecules were co-localized. Flow cytometry analysis demonstrated that the percentages of both CD4+ T cells and CD8+ T cells in the liver and peripheral blood were significantly increased and induced T exhaustion. When the mice were treated with anti-CTLA-4 antibodies, the number and weight of the lesions decreased significantly. Meanwhile, the flow cytometry results suggested that blocking CTLA-4 could effectively reverse T cell exhaustion and reactivate immune function. Our work reveals that blocking CTLA-4 could effectively reverse the T cell exhaustion caused by E. multilocularis and could be used as a novel target for the treatment of AE.
New insight into arginine and tryptophan metabolism in macrophage activation during tuberculosis
Authors: Zhang Kangling , Mishra Abhishek , Jagannath Chinnaswamy
Published: March 2024

Arginine and tryptophan are pivotal in orchestrating cytokine-driven macrophage polarization and immune activation. Specifically, interferon-gamma (IFN-γ) stimulates inducible nitric oxide synthase (iNOS) expression), leading to the conversion of arginine into citrulline and nitric oxide (NO), while Interleukin-4 (IL4) promotes arginase activation, shifting arginine metabolism toward ornithine. Concomitantly, IFN-γ triggers indoleamine 2,3-dioxygenase 1 (IDO1) and Interleukin-4 induced 1 (IL4i1), resulting in the conversion of tryptophan into kynurenine and indole-3-pyruvic acid. These metabolic pathways are tightly regulated by NAD+-dependent sirtuin proteins, with Sirt2 and Sirt5 playing integral roles. In this review, we present novel insights that augment our understanding of the metabolic pathways of arginine and tryptophan following Mycobacterium tuberculosis infection, particularly their relevance in macrophage responses. Additionally, we discuss arginine methylation and demethylation and the role of Sirt2 and Sirt5 in regulating tryptophan metabolism and arginine metabolism, potentially driving macrophage polarization.
New insights into the role of macrophages in cancer immunotherapy
Authors: Zhou Li , Zhao Tiantian , Zhang Ruzhe , Chen Chen , Li Jiwei
Published: March 2024

Macrophages are the main component of the tumor microenvironment, which are differentiated from monocytes in the blood and play an important role in cancer development. Tumor-associated macrophages (TAMs) can promote tumor growth, invasion, metastasis, and resistance to anti–programmed death receptor 1 therapy by regulating programmed cell death ligand 1 expression and interacting with other immune cells in the tumor microenvironment. However, when activated properly, macrophages can also play an anti-tumor role by enhancing the phagocytosis and cytotoxicity of tumor cells. TAM is associated with poor prognosis and drug resistance in patients treated with immunotherapy, indicating that macrophages are attractive targets for combined therapy in cancer treatment. Combination of targeting TAMs and immunotherapy overcomes the drug resistance and achieved excellent results in some cancers, which may be a promising strategy for cancer treatment in the future. Herein, we review the recent findings on the role of macrophages in tumor development, metastasis, and immunotherapy. We focus mainly on macrophage-centered therapy, including strategies to deplete and reprogram TAMs, which represent the potential targets for improving tumor immunotherapy efficacy.
Energy fluxes and vertical heat transfer in the Southern Baltic Sea
Authors: Rak Daniel , Przyborska Anna , Bulczak Anna I. , Dzierzbicka-Głowacka Lidia
Published: March 2024

Introduction

This study investigates the dynamics of energy fluxes and vertical heat transfer in the Southern Baltic Sea, emphasizing the significant role of the dicothermal layer in modulating the penetration of the thermocline and the propagation rates of thermal energy. The research aims to elucidate the complex patterns of solar energy absorption, its conversion into sea surface temperature (SST), and the transference of this energy deeper into the marine environment.

Methods

Data were collected through 93 monitoring cruises by the Institute of Oceanology of the Polish Academy of Sciences (IOPAN) from 1998 to 2023, using a high-resolution towed probe technique alongside Argo floats data for the Baltic Proper from 2020 to 2023. ERA5 climate reanalysis dataset and NEMOv4.0 ocean model forecasts were also utilized for a comprehensive analysis of VITE, Top Net Short-Wave Radiation, SST, and energy budget across the Southern Baltic Sea.

Results and discussion

The Southern Baltic Sea functions as a net energy sink, with an average energy budget of 5.48 W m-2, predominantly absorbing energy during daylight and emitting it from September to February. A 59-day lag between peak solar energy and VITE peak was observed, followed by an additional 6-day delay before peak SST. The study further reveals a 15-day delay in temperature phase shift per 10 meters depth due to the dicothermal layer's influence on thermal energy propagation, extending to 35 days in the Central and Northern Baltic. Heat transfer is significantly affected by the levels of the thermocline and halocline, with regional variations in advection-driven seasonal signals. The pronounced thermal inertia and the critical role of the dicothermal layer underscore the complexity of thermal energy distribution in the Southern Baltic Sea.
Biofilm contamination in confined space stations: reduction, coexistence or an opportunity?
Authors: Marra Daniele , Ferraro Rosalia , Caserta Sergio
Published: March 2024

The prolonged human permanence in confined environments in space, such as in the case of the International Space Station, has inadvertently fostered conditions leading to uncontrolled microbial proliferation on surfaces, known as biofilm. Biofilm presence represents a challenge in critical spacecraft systems, that can lead to contamination issues and systems loss of function due to biofouling phenomena. This scenario is further complicated by microgravity that has a controversial role on biofilm growth and formation. Biocontamination can be a limiting factor in human long-term mission in outer Earth orbit and an economic and health issue on ISS. This study addresses the pressing need for effective antimicrobial strategies against such resilient biofilms in confined environments where the usage of biocidal chemical compounds is strictly controlled due to toxicity dangers. Traditional methods can be complemented by advanced antimicrobial coatings techniques. A promising approach is based on the oxygen plasma as coating platform. The technology can be potentially extended to a wide range of antibiofilm agents (e.g., peptides, bacteriophages, nanoparticles, quorum sensing disrupting agents, etc.) and substrates (e.g., metal, plastic, ceramic) showing an exceptional flexibility. An alternative vision of the biofilm challenge can be inspired by the dual nature of biofilms, addressed as “good” or “bad” depending on the specific application. Indeed, biofilm have a great potential in closed systems as small space habitat (e.g., ISS) that can be inspired by their role in “large space habitat” as planet Earth itself. The replication of such a complex biological equilibrium is an open challenge.