bluuebunny/crossref_metadata_2025 huggingface dataset:
Early-onset type 2 diabetes and tirzepatide treatment: a post hoc analysis from the SURPASS clinical trial program
Authors: Zeitler Philip , J. Galindo Rodolfo , J. Davies Melanie , K. Bergman Brandon , T. Thieu Vivian , Nicolay Claudia , Allen Sheryl , J. Heine Robert , J. Lee Clare
Published: April 2024

Objective: We evaluated baseline characteristics of participants with early-onset T2D from the SURPASS program and tirzepatide’s effects on glycemic control, body weight (BW), and cardiometabolic markers. Research Design and Methods: This post hoc analysis compared baseline characteristics and changes in mean HbA1c, BW, waist circumference (WC), lipids, and blood pressure (BP) in participants (N=3792) with early-onset vs later-onset T2D at Week 40 (SURPASS-1, SURPASS-2) or Week 52 (SURPASS-3). Analyses were performed by study on data from participants while on assigned treatment without rescue medication in case of persistent hyperglycemia. Results: At baseline in SURPASS-2, participants with early-onset vs later-onset T2D were younger with longer diabetes duration (9 vs 7 years, p<0.001) higher glycemic levels (8.5% vs 8.2%, p<0.001), higher BW (97 vs 93 kg, p<0.001) and BMI (35 vs 34 kg/m2, p<0.001), and a similarly abnormal lipid profile (e.g., triglycerides 167 vs 156 mg/dL). At Week 40, similar improvements in HbA1c (-2.6% vs -2.4%), BW (-14 vs -13 kg), WC (-10 vs -10 cm), triglycerides (-26% vs -24%), HDL (7% vs 7%), and systolic BP (-6 vs -7 mmHg) were observed in both subgroups with tirzepatide. Conclusions: Despite younger age, participants with early-onset T2D from the SURPASS program had higher glycemic levels and worse overall metabolic health at baseline vs those with later-onset T2D. In this post hoc analysis, similar improvements in HbA1c, BW and cardiometabolic markers were observed with tirzepatide, irrespective of age at T2D diagnosis. Future studies are needed to determine long-term outcomes of tirzepatide in early-onset T2D.
Effects of a Brief Mindfulness-based Intervention in Patients with Psoriasis: A Randomized Controlled Trial
Authors: Eckardt Markus , Stadtmueller Laura , Zick Christoph , Kupfer Jörg , Schut Christina
Published: April 2024

Mindfulness is a special type of attention, namely focusing on the current moment in a non-judgmental manner. Extensive mindfulness-based interventions have been shown to have positive effects in patients with psoriasis. However, it is unclear whether brief (2-week) interventions are also beneficial. Therefore, the aim of this study was to investigate the effects of a 2-week mindfulness-based intervention in patients with psoriasis. Patients were randomly assigned to an experimental (treatment-as-usual + mindfulness-based intervention) or control group (treatment-as-usual) during their clinic stay. All variables were measured by self-report using validated questionnaires: primary outcomes were mindfulness and self-compassion, secondary outcomes were itch catastrophizing, social anxiety, stress and skin status. Variables were assessed prior to, immediately and 3 months after the intervention. Effects were tested by repeated-measures analysis of variance (ANOVA). Analyses of pre-post-measurements (n = 39) revealed a significant interaction effect on self-reported mindfulness [F(1,35) = 7.46, p = 0.010, η2p = 0.18] and a tendency to a significant effect on self-reported self-compassion [F(1,36) = 3.03, p = 0.090, η2p = 0.08]. There were no other significant effects, but most descriptive data were in favour of the experimental group. However, the control group showed a greater improvement in skin status. Further studies are needed to replicate these findings and investigate which subgroups especially profit from such an intervention.
PEMBENTUKAN MAKNA JUKUGO DALAM TERMINOLOGI PERDAGANGAN JEPANG
Authors: Nisa Nurul Alviatin , Rahayu Ely Triasih , Suryadi Yudi
Published: April 2024

Penelitian ini mengkaji pembentukan makna jukugo. Tujuan dari penelitian ini adalah untuk menjelaskan hubungan makna antar kanji pembentuk jukugo dan pembentukan makna kanji jukugo dalam terminologi perdagangan Jepang. Metode yang digunakan adalah deskriptif kualitatif, sedangkan teknik pengumpulan data yang digunakan adalah teknik simak catat. Teknik analisis data dilakukan menggunakan teknik perluas. Sumber data penelitian ini berupa 12 artikel koran daring Nikkei dan dalam 12 artikel tersebut ditemukan 18 data. Hasil analisis menunjukkan bahwa dari semua kata yang ditemukan makna kanji yang membentuk jukugo semuanya berkaitan dengan makna yang terdapat dalam kamus, dan ditemukan; 1) dua jukugo dengan makna kanji pembentuknya sama atau hampir sama, 2) dua jukugo dengan dua kanji yang memiliki arti berlawanan, 3) tiga belas jukugo yang terdiri dari dua kanji dengan kanji pertama menerangkan kanji, dan 4) satu jukugo yang kanji kedua berfungsi melengkapi atau mempertegas kanji pertama.
PERSONIFIKASI, DEPERSONIFIKASI, DAN MAKNA KIAS DALAM LIRIK LAGU WAGAKKI BAND
Authors: Azhari Fitri , Haryono Haryono , Kurniawan Eko
Published: April 2024

Penelitian ini berjudul Personifikasi, Depersonifikasi, Dan Makna Kias Dalam Lirik Lagu Wagakki Band. Penelitian ini bertujuan untuk 1) mendeskripsikan penggunaan personifikasi dan depersonifikasi dalam lirik lagu Wagakki Band. 2) Mendeskripsikan makna kias yang terkandung dalam lirik lagu Wagakki Band. Penelitian ini menggunakan metode deskriptif kualitatif. Data dikumpulkan dengan cara metode simak catat. Data dalam penelitian berupa penggalan lirik lagu yang mengandung gaya bahasa personifikasi dan depersonifikasi. Sumber data yang digunakan dalam penelitian ini yaitu 19 buah kumpulan lirik lagu Wagakki Band. Berdasarkan hasil analisis, dari 19 buah lirik lagu ditemukan 17 penggunaan gaya bahasa personifikasi dan 13 penggunaan gaya  bahasa depersonifikasi dengan ragam frasa yang ditemukan yaitu 14 penggunaan frasa verba, 8 pengggunaan frasa nomina, dan 8 penggunaan frasa adjektiva. Penggunaan gaya bahasa tersebut memunculkan makna kias yang tidak mendeskripsikan arti yang sebenarnya dan membuat lirik dalam lagu semakin indah.
ELDIRU DALAM PEMBELAJARAN DOKKAI DI MASA PANDEMI COVID-19
Authors: Suryadi Yudi , Puspitasari Diana
Published: April 2024

Penelitian ini dilatarbelakangi oleh kurangnya kemampuan mahasiswa Sastra Jepang Unsoed dalam mata kuliah dokkai (pemahaman bacaan berbahasa Jepang) dan kondisi pandemi Covid-19 yang membuat proses pembelajaran dilakukan secara daring. Penelitian ini bertujuan untuk mendeskripsikan hasil belajar mahasiswa melalui sistem Eldiru dalam mata kuliah dokkai, dan tanggapan mahasiswa terhadap sistem Eldiru tersebut. Metode yang digunakan yaitu metode action research, di mana sumber datanya adalah mahasiswa Sastra Jepang Unsoed semester 2 angkatan 2019, objek penelitiannya yaitu hasil belajar mahasiswa dan tanggapan mahasiswa, serta instrumen penelitian yang digunakan berupa tes dan angket. Berdasarkan hasil tes mahasiswa diketahui bahwa nilai rata-ratanya 87,99 poin, nilai tertinggi 100 poin, dan nilai terendah 50 poin. Berdasarkan hasil angket, mahasiswa berpendapat bahwa kelebihan Eldiru yaitu praktis, lengkap, jelas, terstruktur, efektif, dan efisien. Sebaliknya, kekurangannya yaitu terkadang sistem berjalan lambat, error, kurang stabil, dan menguras kuota data. Kesimpulannya, hasil belajar mahasiswa Sastra Jepang semester 2 angkatan 2019 dalam mata kuliah dokkai melalui sistem Eldiru berada dalam kategori baik, dan berdasarkan hasil tanggapan mahasiswa menunjukkan bahwa sebagian besar mahasiswa setuju dengan penggunaan sistem Eldiru dalam mata kuliah dokkai terutama di masa pandemi Covid-19.
ANALISIS PENGGUNAAN MEDIA MIND MAP PADA PEMBELAJARAN BAHASA JEPANG SECARA DARING DALAM MENINGKATKAN MINAT DAN MOTIVASI BELAJAR SISWA KELAS X BAHASA SMAN 1 BATU
Authors: Milenia Pratika Fitri , Sutiyarti Ulfah , Rini W
Published: April 2024

Penelitian ini bertujuan untuk mendeskripsikan penggunaan media mind map dalam pembelajaran bahasa Jepang siswa kelas X Bahasa SMAN 1 Batu yang dilakukan secara daring. Penelitian ini dilakukan pada tanggal 2 Agustus – 11 September 2021 dengan responden yang berjumlah 20 siswa. Metode penelitian yang digunakan adalah metode deskriptif dengan pendekatan kualitatif. Penelitian ini dalam pengumpulan data menggunakan instrumen observasi, wawancara, dan angket. Angket disebar kepada responden dengan menggunakan Google Form. Kemudian data diperkuat dengan metode wawancara. Penelitian ini menggunakan empat indikator minat belajar, yaitu perasaan senang, ketertarikan, penerimaan, dan keterlibatan siswa. Hasil penelitian menunjukkan bahwa proses pelaksanaan pembelajaran dengan menggunakan media mind map membuat siswa dapat lebih aktif dan berpartisipasi dalam pembelajaran. Indikator perasaan senang, media mind map dapat meningkatkan minat, motivasi, dan menyenangkan. Indikator ketertarikan, meningkatkan fokus dan menarik dalam pembelajaran. Indikator penerimaan, media mind map mudah dipahami dan diterima. Keterlibatan siswa, media mind map mempermudah mengingat kosakata bahasa Jepang.
DEIKSIS BAHASA JEPANG DAN TERJEMAHANNYA DALAM BAHASA INDONESIA
Authors: Fauziyah Lilik , Hamidah Idah , Hartati Hartati
Published: April 2024

Penelitian ini bertujuan untuk mendeskripsikan bentuk deiksis persona bahasa Jepang serta mendeskripsikan padanan deiksis persona bahasa Jepang dalam bahasa Indonesia. Penelitian ini menggunakan teori pragmatik dan teori terjemahan. Sumber data yang digunakan dalam penelitian ini adalah drama Kakegurui Live Action Season 2 dan sumber data tambahan yang digunakan adalah subtitle terjemahan bahasa Indonesia dari drama tersebut. Sedangkan data yang digunakan dalam penelitian ini adalah kutipan dialog yang mengandung deiksis persona. Metode penelitian yang digunakan adalah deskriptif kualitatif dengan teknik simak catat sebagai teknik pengumpulan data. Dalam drama Kakegurui Live Action Season 2 ditemukan 113 data yang mengandung deiksis persona. Berdasarkan konsep kesepadanan penerjemahannya, hasil terjemahan deiksis persona dalam bahasa sasarannya, yakni bahasa Indonesia, sepadan dengan deiksis persona dalam bahasa sumbernya, yakni bahasa Jepang.
METAFORA KONSEPTUAL DALAM ALBUM AO NO WALTZ KARYA EVE KAJIAN SEMANTIK KOGNITIF
Authors: Delfariyadi Fahri , Nur Tajudin
Published: April 2024

Penelitian ini berjudul ‘Metafora Konseptual dalam Album Ao no Waltz Karya Eve: Analisis Semantik Kognitif’. Orientasi penelitian ini adalah makna metafora dan skema citra yang terkandung di dalam album Ao no Waltz. Tujuan dari penelitian ini adalah untuk mendeskripsikan makna metafora dan skema citra yang terdapat di album Ao no Waltz. Teori yang digunakan sebagai landasan berpikir adalah teori metafora konseptual menurut Lakoff dan Johnson (2003) dan teori skema citra menurut Croft dan Cruse (2004). Penelitian ini merupakan penelitian deskriptif kualitatif. Sumber data yang digunakan pada penelitian ini adalah album Ao no Waltz karya Eve dan data diperoleh dengan teknik catat. Adapun hasil dari penelitian ini adalah ditemukan sebanyak delapan belas metafora yang terdiri dari tiga metafora struktural, lima metafora orientasional, dan sepuluh metafora ontologis. Selain itu, skema citra yang ditemukan adalah skema citra force, container, dan identity.
PENERAPAN METODE PROJECT BASED LEARNING “TEMAN JEPANG” MELALUI PENGGUNAAN APLIKASI HELLOTALK UNTUK PEMBELAJARAN MENULIS BAHASA JEPANG
Authors: Hermawan Dhevi Amalia , Amri Miftachul
Published: April 2024

This study aims to describe the application of the “Teman Jepang” project-based learning method through the use of the HelloTalk application for learning to write Japanese and to find out how the students respond after the implementation of the “Teman Jepang” project-based learning method through the use of the HelloTalk application. The method used is a qualitative descriptive method with the primary data collection process through a study of documents and field data, as well as the results of student response questionnaires. The subjects of this study were 196 students from class XII MIPA and class XII Language at SMA Negeri 10 Malang. The results of the data analysis showed that the interest of students in the application of the "Teman Jepang" project-based learning method through the use of the HelloTalk application for learning to write Japanese was at a very high standard. This study concludes that the “Teman Jepang” project-based learning method through the use of the HelloTalk application was successfully applied in learning to write Japanese and received a positive response from students.
MEMBANGUN POLA KOMUNIKASI DAN PENDIDIKAN POLITIK BAGI KALANGAN GEN Z DI SMKN 1 BLADO BATANG
Authors: Setiawan Hendy , Choirunnisa Choirunnisa , Sutinnarto Sutinnarto , Irawan Rizky Rahmanda
Published: April 2024

The purpose of this article is to explain the importance of communication literacy and political education, especially for Gen Z. Especially in the conditions of the political year, communication literacy and political education are guidelines for Gen Z so that they can respond more rationally to their political year. This is important because many Gen Z people are not politically literate, so sometimes political frenzy can expose them to criminal charges. For this reason, communication literacy and political education are important to equip them so they can continue to exist in the political year. This service method uses an active participation approach where this program involves students at SMKN 1 Blado. In its implementation, service members carry out initial observations, location determination, implementation, evaluation, and follow-up of the service program. The results of the service program show that students are very enthusiastic and interested in the political education material presented. They feel that they are still very unfamiliar with politics, so this service program is a source of knowledge for them. Moreover, Gen Z needs literacy. Apart from that, they were also very active in discussing questions and answers, especially how Gen Z behaves politically and rationally in determining their political choices to produce optimal impacts for them.
Darul Hikmah Islamic Boarding School Resilience Agains Radicalism through the Muballighin Program
Authors: Habibi Debi Fajrin
Published: April 2024

Kajian ini bertujuan untuk menganalisis program muballighin sebagai salah satu pemegang peran penting pesantren Darul Hikmah dalam membangun kekuatan besarnya untuk menarasikan toleransi dan moderasi beragama sebagai bentuk resiliensi terhadap paham radikalisme. Penelitian ini merupakan field research dengan mengambil data di lapangan. Metode pengumpulan data yang digunakan yaitu wawancara, observasi dan dokumentasi. Hasil penelitian menunjukkan bahwa secara umum pesantren Darul Hikmah memiliki resiliensi yang kuat dalam menghadapi berbagai persoalan dan tantangan kehidupan berbangsa dan bernegara dengan memiliki kompetensi untuk menyampaikan pesan-pesan keagamaan pada masyarakat yang dilandasi wawasan moderasi beragama.
Gus Baha's Cangkem Elek Movement as a Model of Religious Moderation
Authors: Rozzaq Siddiq Abdur , Toipah Toipah
Published: April 2024

Kelompok ekstrimis terus aktif menyebarkan narasi-narasi ekstrimisnya, terutama di jagat media sosial. Media sosial merupakan ladang hijau bagi kelompok tersebut untuk menyebarluaskan narasi intoleran dan ekstrim. Selain itu, masih banyak kelompok yang menuding bidah kepada kelompok lain ketika ada amalan yang tidak sesuai dengan tafsir teks keagamaan yang dipercayainya. Dalam hal ini, Gus Baha menawarkan sebuah model untuk menjawab tuduhan-tuduhan tersebut dengan gerakan cangkem elek. Jika dianalisis lebih dalam, gerakan cangkem elek ala Gus Baha ini menjadi salah satu model dalam moderasi beragama. Pertanyaannya kemudian, bagaimana gerakan cangkem elek menjadi model dalam moderasi beragama?. Penelitian ini merupakan penelitian berbasis digital. Penulis menyertakan beberapa transkip yang diambil dari video-video pengajian Gus Baha melalui kanal YouTube dan website. Jenis penelitian ini adalah penelitian kualitatif. Penelitian ini menghasilkan beberapa penjelasan mengenai gerakan cangkem elek sebagai model moderasi beragama ala Gus Baha. Gerakan cangkem elek bukanlah sebuah gerakan yang terorganisir maupun terlembaga. Gerakan ini bertujuan untuk meng-counter narasi ekstrimis dengan cara qiyasi dan ketus. Gus Baha melakukan gerakan ini bukan tanpa landasan, melainkan berlandaskan kisah-kisah Alquran dan kisah sahabat Nabi saw. Gerakan cangkem elek pada konteks hari ini merupakan bentuk kontra narasi terhadap narasi narasi ekstrimis. Tidak hanya bagi orang alim, gerakan cangkem elek mengajak kalangan awam untuk ikut menyuarakan kontra narasi ekstrimis. Gerakan yang masif dari akar rumput ini diharapkan dapat menyuarakan moderasi beragama di tingkat nasional maupun internasional.
The Urgency of Islamic Universities in Building Student Character Based on Religious Moderation in the Digital Age
Authors: Sarawati Tia , Mubarok Muhamad Sofi
Published: April 2024

Moderasi beragama dalam era digital saat ini membawa mahasiswa untuk berpikir lebih luas dengan informasi yang mudah didapat. Moderasi beragama menemukan relevansinya untuk dikokohkan di atas dasar filosofi universal dalam konstruk pengembangan keilmuan di Perguruan Tinggi Keagamaan Islam (PTKI). Tujuan dari penelitian ini yaitu untuk mengkaji pentingnya Perguruan Tinggi Islam dalam membangun karakter moderasi beragama pada mahasiswa di era digital yakni dengan memanfaatkan media sosial yang ada. Penelitian ini menggunakan metode deskriptif kualitatif, Teknik pengumpulan data dengan studi pustaka (library research). Teknik analisis data menggunakan analisis isi (content analysis). Hasil dari penelitian ini yaitu moderasi beragama menjadi basis penguatan paham keagamaan melalui ruang digital yang memiliki karakteristik multitasking untuk mengokohkan pemahaman keagamaan yang moderat, toleran dan  penuh kasih sayang. Pentingnya karakter berbasis moderasi beragama bagi mahasiswa yaitu untuk membangun citra sebagai manusia yang kamil dan umat yang khair secara pribadi maupun kolektif yang bersedia dan mampu mengemban amanah dengan menumbuhkan karakter moderasi beragama. Penyampaian moderasi beragama media sosial dapat digunakan sebagai sarana kajian dan dakwah secara daring dan menyebarluaskan paham sikap moderasi beragama. Konten di media sosial yang mengangkat topik mengenai moderasi beragama sudah banyak tersebar dan diciptakan. Hal tersebut umumnya tersebar melalui beberapa media sosial yaitu Instagram, WhatsApp, Facebook, Twitter, Youtube, dan TikTok
KODIFIKASI HISTORIS ILMU FALAK PADA ABAD PERTENGAHAN
Authors: Zahroya Isyvina Unai , Syarif Muh Rasywan
Published: April 2024

This article examines the history of the development of astronomy in the Middle Ages as evidenced by the emergence of reliable Muslim scholars in the history of Muslim scientific civilization. The method used is a literature review by looking at the historical references to the development of astronomy. From the results of the study it was found that the development of Islamic science (1250 AD / 647 H - 1800 AD / 1214 H) in astronomy was divided into 4 periods including the first period which is believed to be the era of assimilation and the initial struggle of Greek, Indian and Sasanid astronomy (Persia). (700 AD / 80 AH – 825 AD / 209 AH), the second period is believed to be a major investigation and acceptance and modification of the Ptolemaic astronomical system (825 AD / 209 H - 1025 AD / 415 H), the third period as a period of advancement of the system Islamic astronomy is believed to be the middle ages of astronomy (1025 AD / 415 H - 1450 AD / 853 H), the fourth period was a period of stagnation in which not many scientific contributions were achieved (1450 AD / 853 H - 1900 AD / 1317 H).
INTEGRASI HISAB RUKYAT AWAL RAMADAN 1442 H DENGAN MODEL VISIBILITAS KASTNER
Authors: Sakirman Sakirman , Utama Judhistira Aria , Zainon Othman bin
Published: April 2024

There is no empirical evidence of the early hilal of Ramadan 1442 H that was observed through technological devices. The justification for witnessing the new moon still refers to the syar'i new moon term, not the astronomical new moon. The country of Brunei Darussalam can be used as an example when the astronomical hilal is not successfully observed, then the beginning of the hijri month is the next day or fulfills the ongoing month and there is no legal tolerance such as the use of the syar'i hilal term to replace the astronomical hilal. The integration of reckoning-rukyat is actually a methodological endeavor to perfect the criteria for the beginning of the Hijri month. Kastner's hilal visibility model is present in an effort to bridge the refinement of the criteria for the beginning of the hijri month. Through the criteria for the visibility of the hilal, Kastner offers a mathematical model that can be used as a role model for observing the hilal. Kastner's hilal visibility mathematical calculation model can be expressed in a curve that can be translated easily. Based on Kastner's hilal visibility, the early hilal of Ramadan 1442 H the hilal cannot be observed with the visual eye. Perukyat's testimony of seeing the hilal at the beginning of Ramadan 1442 H can be rejected by law because it is not based on empirical evidence in the form of a hilal image as a result of visual eye observation. According to Kasnter's hilal visibility model, the visibility of the hilal at the beginning of Ramadan 1442 H reached the maximum hilal visibility with a value of -1.68 for visual observations, the height of the hilal at the same time was 1.56 degrees (height difference between the Moon and the Sun at that time was 4, 46 degrees) with an elongation of 4.70 degrees. Observing the new moon without using tools such as a telescope, will not succeed in detecting the figure of the new moon, because the visibility of the new moon is still negative since sunset.
STUDI TOKOH SYEKH MUHAMMAD ARSYAD AL-BANJARI (1710-1812) ATAS POLEMIK ARAH KIBLAT DI BATAVIA PADA MASA HINDIA BELANDA
Authors: Nur Aisyah Nur Aisyah , Suriyadi  , Suriyadi  , Nur Hidayat
Published: April 2024

Qibla direction is an important issue for Muslims, because facing the Qibla is one of the conditions for the validity of prayer. Scholars agree on the obligation to face the Qiblah. However, they differed in terms of whether what was demanded should be facing the ainul ka'bah (the building) or was it just the direction. In the 12th century H, the famous figure of the Shafi'i School at that time was Sheikh Muhammad bin Sulaiman al-Kurdi (1127-1194 H). He was the main teacher of Sheikh Muhammad Arsyad al-Banjari in the field of fiqh. In 1772 M, when Sheikh Muhammad Arsyad al-Banjari and his three friends returned from Haramain and then stopped by Batavia, he saw the mihrabs there were not facing the Kaaba . He argued that the mihrab should be aligned with the qibla by shifting 25 degrees to the right or north. At that time Sheikh Arsyad changed the Qibla of one of the mosques in Batavia, and then a commotion arose in the people of Jakarta, and received a letter of rebuttal from a sheikh of the congregation at that time Sheikh Abdullah bin Abdul Qohhar al-Jawi. This conflict involved the Governor General of the Dutch East Indies Petrus Albertus van der Parra (1761-1775) and a priest who was an astronomer Johann Mauritz Mohr (1716-1775). And in the end, Sheikh Arsyad's argument was accepted by all parties and the conflict ended peacefully, as documented in his story in the treatise "Mas-alatul Qiblah fil Batawi" written by Sheikh Muhammad Arsyad al-Banjari in 1772 M.
Fecal cytokine profile in preterm infants in the diagnosis of necrotizing enterocolitis: pilot study results
Authors: Kosterina E. E. , Balashova E. N. , Krasnyi A. M. , Kirtbaya A. R. , Rudakova A. A. , Sadekova A. A. , Vtorushina V. V. , Krechetova L. V. , Ionov O. V.
Published: April 2024

In this study, we sought to determine fecal cytokine levels in very preterm newborns at the onset of non-specific clinical symptoms of necrotizing enterocolitis (NEC) and decreased gastrointestinal (GI) motility. The study was approved by the Ethics Committee and the Scientific Council of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after the Academician V. I. Kulakov of Ministry of Healthcare of the Russian Federation. Each patient’s parents gave their informed consent to their child’s participation in the study. The study was conducted at the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after the Academician V. I. Kulakov over the period from June 2020 to December 2022. Fecal samples from preterm neonates with gestational age ≤ 32 weeks treated at the A.G. Antonov ICU were collected daily over their first 14 days of life. Samples from 46 newborns were selected for analysis: fecal samples collected on the day of an enteral feeding intolerance episode and fecal samples from controls who had not developed non-specific clinical symptoms of NEC or decreased GI motility, collected on the day when enteral intake reached 100 ml/kg/day. Based on the results of NEC and decreased GI motility diagnosis, stool samples were retrospectively divided into 3 groups: an NEC group (n = 8), a decreased GI motility group (n = 14) and a control group (n = 24). In the fecal samples of the very preterm newborns with NEC stage ≥ II, there was a significant increase in IL-6, IL-8, IL-10, TNF-a levels at the onset of initial symptoms of the disease. At the same time, the cytokine profile of the feces of the decreased GI motility patients did not differ significantly from the control group in any of the parameters. In cases of NEC, high IL-6, IL-8, IL-10 and TNF-a levels were detected in the patients’ stool at the onset of enteral feeding intolerance, suggesting that the method under investigation (aimed at determining the pro- and anti-inflammatory profile of fecal cytokines) may be a promising new tool for differentiating NEC from decreased GI motility in very preterm newborns.
Triosephosphate isomerase deficiency in a Tunisian case series
Authors: Elleuch Amal , Sirine Bouzid , Imen Boujelben , Bayen Maalej , Messaoudi Taieb , Hassen Kammoun , Faiza Safi
Published: April 2024

Triosephosphate isomerase deficiency (TPID) is the most severe glycolytic enzyme defect associated with a progressive neurologic dysfunction. It typically causes hemolytic anemia, neurodegeneration, and recurrent bacterial infections. TPID is caused by a homozygous or a compound heterozygous mutation in the TPID gene. The most frequent variant is Glu104Asp. We report a case series from three unrelated Tunisian families affected by TPID caused by a homozygous Glu104Asp mutation. These reported cases had severe hemolytic anemia. Informed consent was obtained from patients’ parents.
Diagnosis and Management of Myelodysplastic Syndrome in a Fanconi Anemia Patient: A Case Report
Authors: Alghasi Arash , Yousefi Homayon , Khedri Reza , Mahmoudian-Sani Mohammad-Reza
Published: April 2024

An uncommon genetic condition known as Fanconi anemia (FA) is characterized by bone marrow failure, chromosomal instability, and a high susceptibility to cancer. We report a case study of a patient diagnosed with FA who subsequently developed myelodysplastic syndrome (MDS). Informed consent was obtained from the patient’s parents/legal guardians. Consent for publication was obtained from the patient’s parents/legal guardians. We present a case of a 10-year-old boy with a known diagnosis of FA who experienced a decline in platelet count and subsequent bone marrow abnormalities suggestive of MDS. Cytogenetic analysis confirmed the diagnosis of FA with multiple chromosomal breaks, and flow cytometric analysis supported the diagnosis of MDS with excess blasts. The patient underwent a stem cell transplantation from a full matched donor (his father). Stem cell transplantation from a fully matched related donor can be effective in treating FA and associated complications. The transplantation was complicated by graft-versus-host disease and cytomegalovirus infection, however the child achieved complete normalization and exhibited no signs of diarrhea or dependence on immunosuppressive drugs at the six-month follow-up. The case report emphasizes the significance of multidisciplinary care and close follow-up for pediatric FA and MDS patients, suggesting further research and standardization of diagnostic procedures.
Immune checkpoint inhibitor therapy in children and adolescents with refractory/relapsed Hodgkin lymphoma: a case series
Authors: Tuzova E. A. , Evstratov D. A. , Pshonkin A. V. , Korsantiya M. N. , Fisyun I. V. , Litvinov D. V. , Myakova N. V.
Published: April 2024

Ten-year progression-free survival in children, adolescents and young adults with relapsed/refractory Hodgkin lymphoma (r/r HL) does not exceed 50 %. Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs), such as nivolumab and pembrolizumab, are successfully used for the treatment of adults with r/r HL. In this study, we analyzed our experience of ICI treatment of children and adolescents with r/r HL. This study was retrospective and included patients with r/r HL under 18 years of age, who received ICI therapy. Twenty patients were included. All of them had been treated with BV, 35 % (n = 7) of patients had undergone auto-HSCT before treatment with ICIs. Among all patients, 45% (n = 9) received ICIs for the first refractory relapse, 40 % (n = 8) due to refractory disease progression and 15 % (n = 3) received therapy for the second relapse. Two patients received ICIs in combination with other drugs, the response to therapy in 2 patients was unknown. Nine (56 %) of 16 patients achieved a metabolic response, one patient had no evidence of vital tumor cells based on the results of a biopsy of a lesion positive on positron emission tomography, thus a response was achieved in 10 (63%) patients. The survival rate analysis included 20 patients. Median follow-up from ICIs initiation was 1.2 years (interquartile range: 0.7–1.5 years). The probability of 1-year overall survival (OS) rate reaches 69 % (95 % confidence interval (CI) 46.4–91.6), 2-year OS – 60.4 % (95 % CI 35.1–85.7), 3-year OS – 40.3 % (95 % CI 4–76.6). In this study, we demonstrated the effectiveness of the treatment with ICIs as an element of therapy in children and adolescents with r/r HL, who had not responded to previous lines of therapy, including BV. The patients' parents gave consent to the use of their children's data, including photographs, for research purposes and in publications.
Molecular pathogenesis of T-lymphoblastic lymphoma
Authors: Dneprovskii V. R. , Fedorova A. S. , Abramov D. S. , Volchkov E. V. , Myakova N. V.
Published: April 2024

T-lymphoblastic lymphoma (T-LBL) is one of the most common non-Hodgkin lymphomas in children. According to the 2022 WHO classification, T-LBL and acute T-lymphoblastic leukemia are considered as a single disease since they both have T-cell precursors as a morphological substrate. In recent years, some progress has been made in the treatment of this disease, but the prognosis for relapses and refractory cases remains extremely unfavorable. One of the promising areas that can increase the effectiveness of therapy is the use of new treatment approaches that consider the molecular and biological features of this tumor. This review examines in detail the molecular aspects of the pathogenesis of T-LBL.
Current views on the etiology and pathogenesis of ALK-positive anaplastic large cell lymphoma
Authors: Abramov D. S. , Fedorova A. S. , Volchkov E. V. , Myakova N. V. , Konovalov D. M.
Published: April 2024

ALK-positive anaplastic large cell lymphoma is a mature T-cell lymphoma characterized by translocations that involve the ALK receptor tyrosine kinase coding gene. This illness is known to almost exclusively affect children and young adults. The biology of ALK-positive anaplastic large cell lymphoma is fairly well researched today, with recent studies focusing on the histogenesis of this neoplasm. In this review, we analyze the existing world literature data on the etiology and pathogenesis of this disease.
Conditions for the implementation of the phenomenon of programmed death of neutrophils with the appearance of DNA extracellular traps during thrombus formation
Authors: Sveshnikova A. N. , Adamanskaya E. A. , Panteleev M. A.
Published: April 2024

The formation of DNA extracellular traps of neutrophils (NET-osis) is a mechanism of programmed cell death of leukocytes, which initially has antibacterial and antifungal functions. The ability of neutrophils to become activated upon contact with activated platelets and, in turn, to activate the contact coagulation pathway via DNA traps plays a central role in venous thrombosis and disseminated intravascular coagulation in COVID-19. At the same time, the intracellular signaling that controls NET-osis is extremely poorly understood even for the simplest cases, when this process is caused by lipopolysaccharides of the bacterial cell wall. In this review, we consider the case of NET-osis in thrombosis, for which there are even more questions. We focused on the conditions for NET-osis observation and features in different scenarios.
The results of a study on the effectiveness 37 and safety of treatment with vemurafenib and cytarabine/2-chloro-2′-deoxyadenosine combination in patients with Langerhans cell histiocytosis with BRAFV600E mutation
Authors: Lyudovskikh E. I. , Yevseyev D. A. , Osipova D. S. , Raykina E. V. , Kalinina I. I. , Baydildina D. D. , Popov A. M. , Burtsev E. A. , Bronin G. O. , Fink O. S. , Purbuyeva B. B. , Pristanskova E. A. , Maschan A. A. , Maschan M. A.
Published: April 2024

Here, we report on a new treatment protocol for patients with BRAF-positive Langerhans cell histiocytosis (LCH). To achieve remission in the affected patients, we used vemurafenib (a targeted drug) in combination with cytarabine (Ara-C) and cladribine (2-CdA). The study included 27 patients: 18 children with multisystem LCH with risk organ involvement (RO+) and 9 – with multisystem LCH without risk organ involvement (RO–). The treatment started with a 28-day cycle of vemurafenib, with subsequent discontinuation. On Day 29, Аra-C + 2-СdA chemotherapy cycle № 1 was initiated. Vemurafenib treatment was again started on Day +1 after the Ara-C + 2-CdA cycle. The interval between the cycles was 28 days. Similarly, the next two Аra-C + 2-СdA chemotherapy cycles (№ 2 and № 3) were carried out. Then therapy with vemurafenib was stopped and 3 cycles of 2-CdA were administered. All the patients responded to the treatment quickly: on Day 28, disease activity score decreased from 15 to 2 in the RO+ group and from 4 to 0 in the RO– group. The two-year relapse-free survival in the RO+ group was 82 % (95 % confidence interval 66–100), and 89 % (95 % confidence interval 71–100) in the RO– patients. The overall survival in both groups was 100 %. Our study demonstrates the safety and effectiveness of the treatment with vemurafenib and intermediate-dose 2-CdA and Ara-C in children with multisystem RO+ and refractory LCH. This prospective non-randomized multicenter study was approved by the Independent Ethics Committee (Minutes No. 3e/1-18) and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. It is registered at clinicaltrials.gov under the number NCT03585686. The first patient was enrolled on 22 June 2018, the data collection was stopped on 30 April 2023.
Visual and quantitative assessment of interim 18F-fluorodeoxyglucose-positron emission tomography/computed tomography in children with Hodgkin lymphoma
Authors: Dunaikin M. M. , Shestopalov G. I. , Yadgarov M. Ya. , Kailash Ch. , Kireeva E. D. , Myakova N. V. , Likar Yu. N.
Published: April 2024

The use of risk-adaptive therapy in patients with Hodgkin lymphoma (HL) makes it possible to de-escalate treatment protocols, thereby decreasing the incidence of long-term adverse effects. Metabolic remission as detected by interim positron emission tomography/computed tomography (PET/CT) performed after 2 cycles of chemotherapy is a prognostic factor that could guide further treatment. The generally accepted Deauville 5-point scale (DS) used for the visual assessment of interim PET/CT scans may be prone to inaccuracies. One of the suggested ways to address this problem is to use a quantitative evaluation method (qPET).

   The aim of our study was to determine the level of discrepancy between DS assigned after visual (vDS) and quantitative (qDS) assessment of detected lesions on interim PET/CT images in children with HL.

   The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Interim PET/CT scans of 115 patients with HL (the median age was 14 years) were retrospectively analyzed using the quantitative (qPET) method to determine qDS. Baseline PET/CT scan findings and medical history data were available for all patients. All imaging studies were performed at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology between June 2016 and March 2023. Our results showed that with the above approach (availability of initial PET/CT scans and access to the patient’s medical history), discordance between vDS and qDS was about 30%. There was no difference in the patients with a DS of 4 and 5. In other cases, in 31 (27%) patients, vDS and qDS differed by one score: 25 patients with a qDS of 2 had a vDS of 3; 6 patients with a qDS of 3 had a vDS of 4. Factors independently associated with event-free survival were vDS (hazard ratio (HR) 2.49 (1.26–4.93), p = 0.009) and the presence of a bulky tumor (HR 3.12 (1.10–9.64), p = 0.048). Our comparative analysis revealed a discrepancy between the findings obtained by the visual and quantitative assessment methods. In our study, there were no cases of vDS underestimation and, as a consequence, no patients underwent treatment de-escalation. In HL patients with good tumor volume reduction on CT but ambiguous results of interim PET/CT evaluation performed using the vDS (especially in case of DS4 or DS3), quantification software should be used.
The use of blinatumomab in children with de novo Ph-negative B-lineage acute lymphoblastic leukemia and slow clearance of minimal residual disease
Authors: Popov A. M. , Rumyantseva Yu. V. , Mikhailova E. V. , Bydanov O. I. , Zerkalenkova E. A. , Olshanskaya Yu. V. , Verzhbitskaya T. Yu. , Permikin Zh. V. , Tsaur G. A. , Lagoyko S. N. , Zharikova L. I. , Myakova N. V. , Ponomareva N. I. , Boychenko E. G. , Fechina L. G. , Novichkova G. A. , Karachunskiy A. I.
Published: April 2024

Children with acute lymphoblastic leukemia (ALL) and slow clearance of minimal residual disease (MRD) demonstrate a significantly worse outcome as compared to those with fast response to chemotherapy. Bispecific monoclonal antibody blinatumomab is the key drug for CD19-directed immunotherapy which opens wide opportunities for the elimination of MRD in patients with B-cell precursor ALL (BCP-ALL).

   Aim of the study – to evaluate the effectiveness of blinatumomab for MRD elimination in children with BCP-ALL and slow MRD clearance treated by the “ALL-MB 2015” protocol.

   The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Patients from the “ALL-MB 2015” trial who demonstrated slow MRD clearance at the end of induction were included in the current study. MRD monitoring was performed by multicolor flow cytometry modified with respect to possible CD19 loss during targeted treatment. Threshold of 0.001% was used for MRD positivity definition. Between February 2020 and August 2023, 228 children with de novo Ph-negative KMT2A-negative BCP-ALL were defined as slow MRD responders according to the criteria of the “Moscow-Berlin” group. Fifty of them were treated with blinatumomab because of slow MRD clearance. Blinatumomab course was given immediately after induction in 23 children, after Consolidation I – in 14 patients, after Consolidation II – in 11 patients, while two children received immunotherapy prior to maintenance. After completion of blinatumomab course, 23 patients continued protocol treatment, 21 received maintenance only, two were treated with high-risk blocks and four received hematopoietic stem cell transplantation. Only 2 of 50 (4.0 %) patients remained MRD-positive after completion of blinatumomab course. By the end of December 2023, only two adverse events were registered: one relapse and one remission death. Two-year event-free survival was 94.7 % (standard error 3.6 %), while cumulative incidence of relapse was 2.6 % (standard error 2.7 %). Outcome in these 50 patients was much better in comparison with 178 children with a slow MRD response who did not receive blinatumomab. The use of blinatumomab in children with de novo Ph-negative BCP-ALL with slow MRD clearance allows achieving MRD-negative remission in nearly all cases. Although a longer follow-up is necessary for the reliable conclusion of CD19-directed therapy effectiveness, the promising results are obtained in the current study in this unfavorable patient group.
The influence of temperature on platelet hemostasis induced by various agonists
Authors: Dobrylko I. A. , Volkova A. A. , Gerda B. A. , Mikhailova D. M. , Gambaryan S. P. , Mindukshev I. V.
Published: April 2024

Platelet activation, shape change and aggregation are active processes that can be significantly dependent on the ambient temperature. However, there are conflicting data in the literature regarding the effect of temperature on platelets. In our work, we used a laser diffraction method to investigate the influence of temperature on the reaction of human platelets activated byvarious agonists: ADP, U46619 (thromboxane mimetic), and thrombin (TRAP-6), that act through G-protein coupled receptors, and collagen, that activates the immunoglobulin receptor GPVI. For agonists that activate G-protein coupled receptors, we showed that an increase in temperature causes an acceleration of the initial platelet activation (shape change) and has nosignificant effect on agonist sensitivity (EC50). At the same time, hypothermia at low doses of such agonists potentiates platelet aggregation, which differs significantly from the effect of collagen. With increasing temperature, collagen accelerates platelet aggregation over the entire range of temperatures investigated. In this paper, we showed that the effect of temperature on platelet activation processes depends on both the dose of agonists and the type of activated receptors. In our study, we included healthy volunteers after obtaining a written informed consent. Blood samples were taken in accordance with the guidelines of the I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences and the Declaration of Helsinki. Studies with human erythrocytes were approved by the Ethics Committee of the I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (Protocol No.3–03 dated 2 March 2021 and Protocol No.1–04 dated 7 April 2022).
Statistically significant improvement in hemophilia A control: a retrospective analysis of the effectiveness and safety of emicizumab in children with severe and inhibitor forms of hemophilia A
Authors: Petrov V. Yu. , Lavrentyeva I. N. , Vdovin V. V. , Svirin P. V.
Published: April 2024

Hemophilia A presents a serious problem, especially in its severe and inhibitor forms, leading to severe bleeding and complications. The importance of studying the effectiveness and safety of new treatment approaches, particularly emicizumab, is undeniable for improving the quality of life of patients.

   Aim: to evaluate the effectiveness and safety of emicizumab in the prevention of bleeding in children with severe and inhibitor forms of hemophilia A.

   Ethical approval was not required since the study only involved the use of generalized retrospective data obtained during routine clinical practice. All data were depersonalized. A retrospective analysis of medical records of 45 children treated at the Morozov Children's Hospital from 2006 to 2022 was carried out. The study included two cohorts: those with severe hemophilia A and those with inhibitor forms. The analysis included an assessment of the frequency of bleeding and hemarthrosis episodes, hospital admissions, and adverse reactions. The analysis included data from 45 patients with hemophilia A who underwent treatment with emicizumab from 2018 to 2022. Of these, 30 children had a severe form of hemophilia A, and 15 had an inhibitor form. The median follow-up period for a severe form was 17 months, ranging from 12 to 23 months, while for an inhibitor form, it was 32 months, with a range of 11 to 51 months. In the group with severe hemophilia A, a statistically significant (p < 0.001) reduction in the frequency of all types of bleeding was observed: 96.7 % of children had no episodes of hemarthrosis during emicizumab therapy, compared to 46.7 % of patients previously treated with FVIII concentrates. No spontaneous hemarthrosis was registered. Similar results were observed in the group with an inhibitor form of hemophilia A: 93.3 % of children had no hemarthrosis episodes while using emicizumab compared to 13.3% during previous treatment with bypassing agents. Over the entire follow-up period, there were 3 bleedings in the cohort of children with severe hemophilia A and 1 bleeding in the cohort of children with inhibitor hemophilia A. Prior to the use of emicizumab, out of 391 bleeding episodes that occurred in 45 children, 218 were spontaneous. Adverse events were recorded in 7 children, manifesting as erythema at the injection site after the first or first and second emicizumab injections and resolving spontaneously. There were no other adverse events; 90 % of children with severe hemophilia A and 73.3 % of children with inhibitor hemophilia A did not report any adverse events during the use of emicizumab. Emicizumab demonstrates high effectiveness and safety in the treatment of children with severe hemophilia A, both with and without inhibitors. The drug significantly reduces the frequency of bleeding episodes and improves the quality of life of patients.
Do you remember about azelastine?
Authors: Groblewska Anna
Published: April 2024

The most common ocular allergy disease is allergic conjunctivitis. Allergic conjunctivitis is reported to affect approximately 20% of general population. It is the result of hypersensitivity response to airborne allergens, pollen, animal dander, fungi (among them molds). It is often underdiagnosed and undertreated. The large surface area of the conjunctiva, a robust vascular supply and a dense concentration of mast cells make allergic conjunctivitis a particularly vexing form of allergy. Nowadays, the dual action agents, among them azelastine, with combines antihistaminic activity with mast cell stabilizing properties are the gold standard for ocular allergy treatment.
Chory z zapaleniem zatok przynosowych w praktyce lekarza rodzinnego
Authors: Rapiejko Piotr
Published: April 2024

Leczenie ostrego powirusowego zapalenia zatok przynosowych, ostrego bakteryjnego zapalenia zatok przynosowych, przewlekłego zapalenia zatok przynosowych i przewlekłego zapalenia zatok przynosowych z polipami nosa opiera się na terapii przeciwzapalnej z użyciem donosowych glikokortykosteroidów oraz płukaniu jam nosa roztworem 0,9% NaCl. Glikokortykosteroidoterapia donosowa w leczeniu zapalenia zatok przynosowych jest skuteczna, co potwierdziły wyniki licznych badań, i bezpieczna, zmniejsza objawy związane z chorobą oraz poprawia jakość życia. Wpływ tego rodzaju leczenia na redukcję objawów jest większy w przypadku zapalenia zatok przynosowych z polipami niż w przypadku zapalenia bez polipów. Udowodniono, że glikokortykosteroidoterapia donosowa zmniejsza polipy nosa oraz sprzyja zapobieganiu ich nawrotom po endoskopowych operacjach zatok.Artykuł prezentuje aktualny stan wiedzy na temat diagnostyki i leczenia zapaleń zatok przynosowych i został przygotowany z myślą o wykorzystaniu w praktyce lekarzy rodzinnych i nielaryngologów oraz przez farmaceutów.