bluuebunny/crossref_metadata_2025 huggingface dataset:
THE DIGITAL FRONTIER: STRATEGIES AND TOOLS FOR CULTIVATING EDUCATIONAL-STRATEGIC COMPETENCE FOR PRE-SERVICE TEACHERS
Authors: Svyrydiuk Vira , Bodyk Ostap , Kalinina Larysa , Prokopchuk Nataliya , Khrystych Nina
Published: June 2024

Digital tools constitute an integral component in the organization of contemporary foreign language environment. The incorporation of Internet technologies into the educational process stimulates the cognitive activity of learners. This article explores potential avenues for cultivating educational-strategic competence in German-language writing through the use of the MOODLE educational platform and Padlet board. The scientific novelty of the research is that overcoming barriers by pre-service teachers in using the educational platform Moodle and the Padlet board ensures the formation of educational-strategic competence in German language writing and intercultural communicative competence. The authors examine the tasks and skills associated with educational-strategic competence, aiming at enhancing the writing skills of pre-service teachers and foster further intercultural foreign language communicative competence.
A theoretical analysis of the relevant literature regarding the integration of innovative techniques into the educational process for pre-service teachers is presented. The didactic possibilities of digital tools during the production of German-language texts are investigated. The article presents metacognitive, cognitive, and communicative learning strategies based on the utilization of digital tools in detail. The authors provide detailed descriptions of language material teaching strategies within the context of intercultural communication.
The intercultural aspect of teaching strategies, which serves as a prominent regulator in the conditions of intercultural communication, is highlighted. The results of applying internet technologies in the educational foreign language process are represented through a survey, indicating their relevance and effectiveness in developing language and communication strategies, both socio-affective and linguistic. Attention is drawn to the potential for modeling foreign language socio-communicative situations through the use of digital tools.
The article emphasizes the importance of digital tools in formative and summative assessment for written skills activities. Pre-service teachers are encouraged to overcome psychological barriers to the effective implementation of innovative techniques, as digitalization is an inseparable component of contemporary society and education.
ВИКОРИСТАННЯ ЗАСОБІВ ІКТ ДЛЯ РОЗВИТКУ НАВИЧОК АУДІЮВАННЯ ЗДОБУВАЧІВ ВИЩОЇ ОСВІТИ
Authors: Башманівська Любов , Башманівська Ірина , Кучерук Оксана , Юрчук Олена , Башманівський Валерій
Published: June 2024

The article deals with the use of information and communication technologies (ICT) as an essential component in the development of listening skills among higher education learners in the process of foreign language education. It also clarifies the concept of ICT and suggests criteria for selecting ICT tools that may be applied in the development of listening skills of higher education learners as an important condition for language. Additionally, it discusses the importance of communicative competence and its role in the learners' learning process in higher education institutions. The study emphasizes the significance of listening orientation in the learning process of a foreign language and Ukrainian as a foreign language, in particular, in educational institutions. The article suggests effective ICT means for developing listening skills in foreign languages, including the use of virtual learning platforms, interactive virtual scenarios, podcasts, audiobooks, interactive tasks, speech recognition technologies, language apps, online lectures, and videos demonstrating various approaches to using ICT for the development of listening skills in higher education institutions. In addition to the aforementioned, it presents tools for developing listening skills in the process of learning Ukrainian as a foreign language in a higher education institution, contributing to the improvement of perceptual and understanding skills, pronunciation development, and vocabulary expansion, in particular, the use of audio recordings for listening to dialogues, audio books, podcasts in Ukrainian, interactive audio games; creating exercises using modern Internet platforms.The article concludes that the use of ICT in the development of students' listening skills in the process of foreign language education is a necessity today, especially in the conditions of quarantine restrictions and the full-scale war in Ukraine. It highlights that ICT tools have the potential to stimulate the improvement of communicative skills, positively impacting the organization of the entire language education process through their informativeness, reliability, visual aids, and the intensification of learning.
МОДЕЛЬ ГЕОІНФОРМАЦІЙНОЇ ПІДГОТОВКИ ФАХІВЦІВ З КАРТОГРАФІЇ У КИЇВСЬКОМУ НАЦІОНАЛЬНОМУ УНІВЕРСИТЕТІ ІМЕНІ ТАРАСА ШЕВЧЕНКА
Authors: Бондаренко Едуард , Дудун Тетяна
Published: June 2024

A wide range of tasks of varying complexity based on the use of spatial data can be effectively performed by professionals with basic or full higher education who have relevant geoinformation training. Cartographers are fully included in the list of professionals, whose geoinformation component significantly affects the level of competencies formed during the educational process at higher education institutions and potential demand from employers.
The model of geoinformation training for cartographers has been tested within accredited educational programs of the first (bachelor’s) and second (master’s) levels of higher education, which operate at Taras Shevchenko National University of Kyiv and are unique in Ukraine.
The invariant components of the model define the goals and content of geoinformation training, means and methods of their achievement, forms of organization of the educational process in the context of acquiring information and communication competencies, the subject-object composition, characteristics of the educational environment, and student learning outcomes.
The proportion of mandatory and elective educational components directly providing geoinformation training at the first level is 24% of the total program volume for “Cartography, Geographic Information Systems, Earth Remote Sensing” and 34.5% at the second level for “Cartography and Geographic Information Systems” programs.
The logical sequence of placing the educational components of these educational programs in the developed curricula by the authors contributes to the consecutive formation and development of knowledge of the theory, methodology, and practice of applying geoinformation systems.
The optimal forms of educational activities in geoinformation training disciplines have been identified, with lectures and practical classes having a predominant ratio of hours in the structure as 1:1.
Discurso televisado del Sr. Presidente del Gobierno, Adolfo Suárez González, sobre promoción de la Ley para la Reforma Política, de 10 de septiembre de 1976
Authors: Suárez González Adolfo , Fuentes Aragonés Juan Francisco
Published: June 2024

Discurso televisado del Sr. Presidente del Gobierno, Adolfo Suárez González, sobre promoción de la Ley para la Reforma Política, de 10 de septiembre de 1976 (Se acompaña comentario «Una ley trascendental y un personaje decisivo» de Juan Francisco Fuentes Aragonés)
Parlamento y grupos de interés: la regulación autonómica de la actividad informal de influencia
Authors: Sanjurjo Rivo Vicente A.
Published: June 2024

La crisis financiera de finales de la primera década del presente siglo originó en nuestro país una crisis sistémica que ocasionó, entre otras cosas, un distanciamiento entre los electores y sus representantes y, con ello, la enésima crisis o aparente crisis de representación. En ese contexto, las comunidades autónomas, algunas de ellas alentadas también por las últimas reformas estatutarias, implementaron una serie de mecanismos orientados a paliar este distanciamiento, agravado por la proliferación de casos de corrupción y que estaba en la raíz del sentimiento de desafección política que aquejaba a buena parte de la sociedad española. Al hilo de todo ello, algunas autonomías emprendieron la regulación de los lobbies a fin de someter su participación en los centros de decisión política a ciertas pautas de transparencia y a reglas éticas de comportamiento. Esta regulación es objeto de análisis en este trabajo y, en particular, la efectuada con relación al lobby parlamentario por el legislador autonómico catalán, el único que, por el momento, la ha materializado.
RESPONSIVITAS PELAYANAN TERHADAP PASIEN LANSIA DI PUSKESMAS GANDUS KOTA PALEMBANG
Authors: Holqiah Husni , Isabella Isabella , Febriyanti Doris
Published: June 2024

Permenkes RI Nomor 67 tahun 2015 menyatakan penyelenggaraan pelayanan kesehatan lansia di Puskesmas dilaksanakan dengan memberikan pelayanan yang bermutu, dan santun terhadap pasien lansia. Memberikan kemudahan dalam pelayanan kepada pasien lansia, seperti memiliki alur pelayanan pasien lansia yang jelas dan mudah, mengutamakan lansia dari pasien umum dan mengingat lemahnya daya tahan tubuh pada lansia. Namun dalam pelaksanaannya masih terdapat keluhan pasien mengenai waktu pelayanan dan ketidakpuasan pelanggan, fenomena ini juga dialami di Puskesmas lain. Hal ini dapat menjadi indikasi kurang tanggapnya pihak Puskesmas dalam menangani atau merespon permasalahan. Tujuan penelitian ini ialah untuk mengetahui responsivitas pelayanan kepada pasien lansia di Puskesmas Gandus Kota Palembang. Dengan menggunakan metode penelitian kualitatif, yang di dapat data observasi, wawancara dan studi dokumentasi sebagai teknik pengumpulan data. Penelitian ini menggunakan teori responsivitas dalam pelayanan publik untuk mengukur responsivitas Puskesmas Gandus. Berdasarkan hasil penelitian, daya tanggap pelayanan terhadap pasien lansia masih perlu ditingkatkan. Pendaftaran online seperti aplikasi, website atau dapat memalui via whatsapp sangat diharapkan agar tidak perlu terlalu lama menunggu layanan pendaftaran.
PUBLISH OR PERISH: ANALISIS BIBLIOMETRIKA PERAN MEDIA SOSIAL TERHADAP PROMOSI PARIWISATA TAHUN 2021-2022
Authors: Kole Hamid , Arjulan Arjulan , Sudirman Faturachman Alputra , Asriani Asriani , Saidin Saidin
Published: June 2024

Penelitian ini bertujuan untuk menganalisis peran media sosial dalam promosi pariwisata pada tahun 2021-2022 melalui pendekatan bibliometrika. Dengan mengumpulkan dan menganalisis data dari artikel-artikel terindeks tentang pariwisata dan media sosial, kami akan mengeksplorasi tren, pola, dan dampak penggunaan media sosial dalam mempromosikan destinasi pariwisata. Metode analisis bibliometrik akan digunakan untuk mengidentifikasi jumlah publikasi, kolaborasi penelitian, serta kata kunci yang paling umum terkait topik ini. Hasil dari penelitian ini diharapkan dapat memberikan wawasan yang berharga bagi pihak-pihak yang terlibat dalam industri pariwisata dan strategi pemasaran melalui media sosial.
Peranan Masyarakat Sipil dalam Peningkatan Akuntabilitas Birokrasi Melalui Pengawasan Publik yang Aktif
Authors: Maritza Dhiya Fahriyyah , Taufiqurokhman Taufiqurokhman
Published: June 2024

Peran masyarakat sipil dalam mendorong akuntabilitas birokrasi tidak dapat diabaikan karena masyarakat sipil memiliki tanggung jawab penting melalui pengawasan publik. Tujuan dari artikel ini adalah untuk menganalisis peran kunci masyarakat sipil dalam mendorong akuntabilitas birokrasi dari sudut pandang pengawasan publik. Penelitian ini menggunakan metodologi kualitatif dan berfokus pada studi kasus berbagai organisasi masyarakat sipil yang telah berhasil memantau kinerja birokrasi dengan menggunakan tinjauan literatur yang komprehensif untuk mengeksplorasi temuan-temuan penelitian terbaru. Beberapa teori yang relevan yaitu teori akuntabilitas publik oleh Bovens. Teori ini menekankan pentingnya transparansi, pertanggungjawaban, dan responsibilitas dalam menjaga akuntabilitas birokrasi. Selain itu, teori pengawasan publik dalam peranan ombudsman juga mengemukakan bagaimana masyarakat sipil dapat menjalankan perannya dalam mengawasi kinerja birokrasi. Lalu teori terakhir, teori partisipasi masyarakat sipil oleh Putnam menyoroti pentingnya partisipasi aktif masyarakat dalam proses pengambilan keputusan untuk meningkatkan akuntabilitas birokrasi. Hasil penelitian menunjukkan peran masyarakat sipil dalam mengawasi dan meningkatkan akuntabilitas birokrasi pemerintah sangat penting. Melalui berbagai mekanisme seperti pengawasan publik, pemantauan anggaran, penyelidikan korupsi, dan advokasi reformasi. Ada beberapa faktor yang memengaruhi efektivitas keterlibatan masyarakat sipil, termasuk tingkat partisipasi warga, akses terhadap informasi, dukungan dari entitas pemerintah, dan kemampuan organisasi masyarakat sipil itu sendiri.
Skutterudite: Reproducibility of Thermoelectric Performance of P-type RyFe4-xCoxSb12 Bulky Compacts
Authors: Kim Jin-Sol , Shin Dong-Kil , Park Kwan-Ho , Kim Il-Ho
Published: June 2024

Skutterudite compounds have excellent thermoelectric performance in the intermediate-to high temperature range. Their lattice thermal conductivity can be reduced by intensifying phonon scattering through independent vibrations of the guest atoms, by filling the voids within the lattice. Furthermore, the thermoelectric figure of merit (ZT) can be enhanced by optimizing the carrier concentration through charge compensation between transition elements. In this study, we compared the thermoelectric properties of p-type filled skutterudite materials, RyFe4-xCoxSb12, where R represents rare-earth elements (La/Ce/Pr/Nd/Yb), which were filled in the voids, and Co was charge-compensated at the Fe site. In the case of LayFe4-xCoxSb12, the introduction of La filling and Co doping led La0.9Fe3CoSb12 to exhibit a high power factor and low thermal conductivity (ZT = 0.67 at 723 K). In the case of CeyFe4-xCoxSb12, in addition to Ce filling, the substitution of Co for Fe resulted in additional lattice scattering, leading to a decrease in thermal conductivity. However, CeFe4Sb12 exhibited a maximum performance of ZT = 0.70 at 823 K. In the case of PryFe4-xCoxSb12, the thermal conductivity was reduced through phonon scattering induced by Pr filling and additional lattice scattering caused by Co substitution; as a result, Pr0.8Fe3CoSb12 exhibited ZT = 0.89 at 723 K. In the case of NdyFe4-xCoxSb12, the phonon scattering was enhanced by adjusting the filling of Nd and substitution of Co, resulting in a lower thermal conductivity; Nd0.9Fe3.5Co0.5Sb12 exhibited ZT = 0.91 at 723 K. For YbyFe4-xCoxSb12, Yb0.9Fe3CoSb12 exhibited a thermoelectric performance of ZT = 0.56 at 823 K. In addition, in this study, for the fabrication (application) of thermoelectric modules, the p-type Nd0.9Fe3.5Co0.5Sb12 skutterudite, which exhibited the best thermoelectric performance, was prepared in bulky compacts to verify the uniformity and reproducibility of its thermoelectric performance.
ÇÖLYAK TANILI BİREYLERİN MOTOR BECERİ VE DİKKAT DÜZEYLERİNİN DEĞERLENDİRİLMESİ- PİLOT ÇALIŞMA
Authors: Ciledag Filiz , Kuş Nuran , Özbay Tuğçe Simay , Sinanoğlu Berçem
Published: June 2024

Çölyak hastalığı dünyada yaklaşık %1 oranında görülmektedir. Başta Gastrointestinal Sistem (GİS) problemleri olmak üzere, çölyak hastalığı; nöroloji, psikiyatri, immünoloji kaynaklı birçok durumla ilişkilendirilmektedir. Sebep olabileceği ekstaintestinal problemler göz önüne alındığında çölyak hastalığı olan bireylerin motor beceri ve dikkat düzeyleri etkilenmiş olabilir. Araştırmada 22-60 yaş arası ek nörolojik ve ortopedik problemi bulunmayan çölyak hastası ve sağlıklı bireylerin motor beceri düzeyleri ‘Zamanlı Kalk Yürü Testi’ ve ‘Zamanlı Merdiven İnip Çıkma Testi’ ile, dikkat düzeyleri ‘Erişkin Dikkat Eksikliği ve Hiperaktivite Bozukluğu Kendi Bildirim Ölçeği’ ile değerlendirilmiştir. Grupların yaş ortalamaları benzerdi (p>0.05). Motor beceri değerlendirmesinden Merdiven İnip Çıkma Testi istatistiksel olarak anlamlı bulundu (p0.05). Çalışmamıza göre çölyak hastalığı olan bireylerde motor beceri etkilenimi görülmektedir. Gelecekteki çalışmalarda çölyak hastalığı olan bireylerin daha büyük örneklem gruplarında ve daha bütüncül olarak değerlendirilmesi gerekmektedir.
An ex vivo method to evaluate vasoactivity induced by hemoglobin-based oxygen carriers in resistance vessels
Authors: Yu Hang , Gao Daoyuan , You Guoxing , Li Weidan , Wang Ying , Chen Yuzhi , Zhao Lian
Published: June 2024

Red blood cell substitutes offer a solution to the problem of blood shortage and side effects of blood transfusion. Hemoglobin-based oxygen carriers (HBOCs) are one of the promising substitutes for red blood cells. Vasoactivity, which refers to the side effect of HBOCs that causes vasoconstriction and subsequent hypertension, limits the clinical application of HBOCs. In this study, an ex vivo method for the evaluation of vasoactivity induced by HBOCs was established based on isolated rat mesenteric artery vessels and the DMT120CP system. The DMT120CP system, equipped with a flowmeter, permits the control of intravascular pressure, pressure gradient, and flow conditions with high accuracy, simulating the physiological conditions for isolated vessels. The concentration of noradrenaline was optimized to 1 × 10−6∼3 × 10−6 M. PEGylated bovine hemoglobin (PEG-bHb) was synthesized and perfused into the vessel for vasoactivity evaluation, with bHb as the positive control and PSS buffer solution as the negative control. PEG-bHb showed a hydration diameter of 15.5 ± 1.4 nm and a P50 value of 6.99 mmHg. PEG-bHb exhibited a colloid osmotic pressure of 64.1 mmHg and a viscosity of 1.73 cp at 40 mg/mL. The established vasoactivity evaluation method showed significant differences in samples (bHb or PEG-bHb) with different vasoactivity properties. The vasoconstriction percentage induced by PEG-bHb samples synthesized in different batches showed coefficients of variation less than 5%, indicating good applicability and repeatability. The established evaluation method can be applied to study the vasoactivity induction and elimination strategies, promoting the clinical application of HBOCs.
A noval noninvasive targeted therapy for osteosarcoma: the combination of LIFU and ultrasound-magnetic-mediated SPIO/TP53/PLGA nanobubble
Authors: Ren Honglei , Xiang Shanlin , Liu Aiguo , Wang Qian , Zhou Nian , Hu Zhenming
Published: June 2024

Purpose

Osteosarcoma (OS) is the most common type of primary malignant bone tumor. Transducing a functional TP53 gene can effectively inhibit OS cell activity. Poly lactic acid-glycolic acid (PLGA) nanobubbles (NBs) mediated by focused ultrasound (US) can introduce exogenous genes into target cells in animal models, but this technique relies on the passive free diffusion of agents across the body. The inclusion of superparamagnetic iron oxide (SPIO) in microbubbles allows for magnetic-based tissue localization. A low-intensity-focused ultrasound (LIFU) instrument was developed at our institute, and different intensities of LIFU can either disrupt the NBs (RLI-LIFU) or exert cytocidal effects on the target tissues (RHI-LIFU). Based on these data, we performed US-magnetic-mediated TP53-NB destruction and investigated its ability to inhibit OS growth when combined with LIFU both in vitro and in vivo.

Methods

Several SPIO/TP53/PLGA (STP) NB variants were prepared and characterized. For the in vitro experiments, HOS and MG63 cells were randomly assigned into five treatment groups. Cell proliferation and the expression of TP53 were detected by CCK8, qRT-PCR and Western blotting, respectively. In vivo, tumor-bearing nude mice were randomly assigned into seven treatment groups. The iron distribution of Perls’ Prussian blue-stained tissue sections was determined by optical microscopy. TUNEL-DAPI was performed to examine apoptosis. TP53 expression was detected by qRT-PCR and immunohistochemistry.

Results

SPIO/TP53/PLGA NBs with a particle size of approximately 200 nm were prepared successfully. For in vitro experiments, ultrasound-targeted transfection of TP53 overexpression in OS cells and efficient inhibition of OS proliferation have been demonstrated. Furthermore, in a tumor-bearing nude mouse model, RLI-LIFU-magnetic-mediated SPIO/TP53/PLGA NBs increased the transfection efficiency of the TP53 plasmid, resulting in apoptosis. Adding RHI-LIFU to the treatment regimen significantly increased the apoptosis of OS cells in vivo.

Conclusion

Combining LIFU and US-magnetic-mediated SPIO/TP53/PLGA NB destruction is potentially a novel noninvasive and targeted therapy for OS.
Molecular characterization of vaginal microbiota using a new 22-species qRT-PCR test to achieve a relative-abundance and species-based diagnosis of bacterial vaginosis
Authors: Oyenihi Ayodeji B. , Haines Ronald , Trama Jason , Faro Sebastian , Mordechai Eli , Adelson Martin E. , Osei Sekyere John
Published: June 2024

Background

Numerous bacteria are involved in the etiology of bacterial vaginosis (BV). Yet, current tests only focus on a select few. We therefore designed a new test targeting 22 BV-relevant species.

Methods

Using 946 stored vaginal samples, a new qPCR test that quantitatively identifies 22 bacterial species was designed. The distribution and relative abundance of each species, α- and β-diversities, correlation, and species co-existence were determined per sample. A diagnostic index was modeled from the data, trained, and tested to classify samples into BV-positive, BV-negative, or transitional BV.

Results

The qPCR test identified all 22 targeted species with 95 – 100% sensitivity and specificity within 8 hours (from sample reception). Across most samples, Lactobacillus iners, Lactobacillus crispatus, Lactobacillus jensenii, Gardnerella vaginalis, Fannyhessea (Atopobium) vaginae, Prevotella bivia, and Megasphaera sp. type 1 were relatively abundant. BVAB-1 was more abundant and distributed than BVAB-2 and BVAB-3. No Mycoplasma genitalium was found. The inter-sample similarity was very low, and correlations existed between key species, which were used to model, train, and test a diagnostic index: MDL-BV index. The MDL-BV index, using both species and relative abundance markers, classified samples into three vaginal microbiome states. Testing this index on our samples, 491 were BV-positive, 318 were BV-negative, and 137 were transitional BV. Although important differences in BV status were observed between different age groups, races, and pregnancy status, they were statistically insignificant.

Conclusion

Using a diverse and large number of vaginal samples from different races and age groups, including pregnant women, the new qRT-PCR test and MDL-BV index efficiently diagnosed BV within 8 hours (from sample reception), using 22 BV-associated species.
Engineered exosomes: a potential therapeutic strategy for septic cardiomyopathy
Authors: Mao Lixia , Liu Songtao , Chen Yongxia , Huang Huiyi , Ding Fenghua , Deng Liehua
Published: June 2024

Septic cardiomyopathy, a life-threatening complication of sepsis, can cause acute heart failure and carry a high mortality risk. Current treatments have limitations. Fortunately, engineered exosomes, created through bioengineering technology, may represent a potential new treatment method. These exosomes can both diagnose and treat septic cardiomyopathy, playing a crucial role in its development and progression. This article examines the strategies for using engineered exosomes to protect cardiac function and treat septic cardiomyopathy. It covers three innovative aspects: exosome surface modification technology, the use of exosomes as a multifunctional drug delivery platform, and plant exosome-like nanoparticle carriers. The article highlights the ability of exosomes to deliver small molecules, proteins, and drugs, summarizing several RNA molecules, proteins, and drugs beneficial for treating septic cardiomyopathy. Although engineered exosomes are a promising biotherapeutic carrier, they face challenges in clinical application, such as understanding the interaction mechanism with host cells, distribution within the body, metabolism, and long-term safety. Further research is essential, but engineered exosomes hold promise as an effective treatment for septic cardiomyopathy.
Am I prepared for Calculus? An action-research study of female students emerging from patriarchy
Authors: Waheed Saira , Pilotti Maura A. E. , AbdelSalam Hanadi M.
Published: June 2024

In this action-research study, the inquiry phase aims to examine the extent to which self-evaluations of Math prerequisite competency relate to the past and current Math performance of STEM female students from a society emerging from strict patriarchy. Its ancillary aim is to determine whether attitudes toward Math and its instruction and assessment are related to past and current performance. Undergraduate Engineering and Computer Science students were surveyed at the start of a Calculus course. As per earlier courses, Calculus was taught through an inquiry-based learning model. Findings illustrated that Math prerequisite competency was underestimated relative to past performance but accurate relative to current performance. Positive attitudes towards Math were correlated with past but not current performance. Students’ preferences for modes of instruction and assessment suggested areas of improvement. During the pragmatic phase of the study, these findings informed instructional changes to enhance Math learning in Engineering and Computer Science.
Individualized luteal phase support in frozen-thawed embryo transfer after intramuscular progesterone administration might rectify live birth rate
Authors: Boynukalin Fazilet Kübra , Tohma Yusuf Aytac , Yarkıner Zalihe , Gultomruk Meral , Bozdag Gürkan , Ozkavukcu Sinan , Bahçeci Mustafa , Demir Berfu
Published: June 2024

Background

The serum P concentrations are suggested to have an impact on pregnancy outcome. However there is no consensus about the optimal progesterone cut-off during the luteal phase. Few studies evaluated the effectiveness of a “rescue protocol” for low serum P concentrations and most of these studies used vaginal progesterone administration. There is paucity of data on the effectiveness of rescue protocol using intramuscular progesterone (IM-P) in frozen-thawed embryo transfer (FET).

Methods

This study is a retrospective cohort study included 637 single or double blastocyst FETs with artificially prepared endometrium receiving 100 mg IM progesterone (P) after incremental estrogen treatment. Serum P concentrations were evaluated using blood samples obtained 117-119 hours after the first IM-P administration and 21 ± 2 hours after the last IM-P administration. Patients with serum P concentrations <20.6 ng/ml on the ET day were administrated 400 mg vaginal progesterone for rescue.

Results

Demographic and cycle characteristics were similar between patients receiving rescue vaginal P (embryo transfer (ET)-day P concentration < 20.6 ng/ml) and patients who did not need rescue vaginal P (ET-day P concentration ≥ 20.6 ng/ml). Clinical pregnancy, miscarriage, and live birth rates were similar between two groups: 52.9%(45/85) vs 59.6%(326/552), p=0.287; 11.1%(5/45) vs 14.1%(46/326), p=0.583; and 47.1%(40/85) vs 50.7%(280/552), p=0.526, respectively. Logistic regression analysis revealed that the female age (p = 0.008, OR=0.942, 95% CI = 0.902–0.984) and embryo quality (ref: good quality for moderate: p=0.02, OR=0.469, 95% CI =0.269–0.760; for poor: p=0.013, OR= 0.269, 95% CI = 0.092–0.757) were independent variables for live birth. Following rescue protocol implementation, ET-day P concentration was not a significant predictor of live birth.

Conclusions

Rescue vaginal P administration for low ET day serum P concentrations following IM-P yields comparable live birth rates.
The dualistic role of Lyn tyrosine kinase in immune cell signaling: implications for systemic lupus erythematosus
Authors: L’Estrange-Stranieri Elan , Gottschalk Timothy A. , Wright Mark D. , Hibbs Margaret L.
Published: June 2024

Systemic lupus erythematosus (SLE, lupus) is a debilitating, multisystem autoimmune disease that can affect any organ in the body. The disease is characterized by circulating autoantibodies that accumulate in organs and tissues, which triggers an inflammatory response that can cause permanent damage leading to significant morbidity and mortality. Lyn, a member of the Src family of non-receptor protein tyrosine kinases, is highly implicated in SLE as remarkably both mice lacking Lyn or expressing a gain-of-function mutation in Lyn develop spontaneous lupus-like disease due to altered signaling in B lymphocytes and myeloid cells, suggesting its expression or activation state plays a critical role in maintaining tolerance. The past 30 years of research has begun to elucidate the role of Lyn in a duplicitous signaling network of activating and inhibitory immunoreceptors and related targets, including interactions with the interferon regulatory factor family in the toll-like receptor pathway. Gain-of-function mutations in Lyn have now been identified in human cases and like mouse models, cause severe systemic autoinflammation. Studies of Lyn in SLE patients have presented mixed findings, which may reflect the heterogeneity of disease processes in SLE, with impairment or enhancement in Lyn function affecting subsets of SLE patients that may be a means of stratification. In this review, we present an overview of the phosphorylation and protein-binding targets of Lyn in B lymphocytes and myeloid cells, highlighting the structural domains of the protein that are involved in its function, and provide an update on studies of Lyn in SLE patients.
Accelerated clinical response achieved by combining short-term tumor-directed photodynamic therapy with immunotherapy-based systemic therapies in synchronous colorectal cancer with MSI-H and POLE mutation: a case report
Authors: Wang Yuhan , Gao Lei , Ma Bin , Shi Jianming , Yin Zhenyu , Zhu Weidong , Chen Hao
Published: June 2024

Genetic sequencing has revolutionized immunotherapy in colorectal cancer (CRC). Recent clinical trials have revealed a positive response to immunotherapy-based systemic therapies in CRC patient subgroups with microsatellite instability (MSI)-High or DNA polymerase epsilon (POLE) mutation. However, the unsatisfactory response rates was the major limitation in real-world practice of the precision immunotherapy in CRC. Adding photodynamic therapy (PDT) to systemic immunotherapy has showed synergetic anti-tumor effect by modulating tumor microenvironment, while the eligible patient’s subgroups which would benefit from this combination remained equivocal. Here we reported a synchronous colorectal cancer patient with MSI-High and POLE mutation who had accelerated response in less than 2 cycles (42 days) of immunotherapy-based systemic therapies after tumor-directed PDT and has remained progression-free by far. This case enlightened the synergetic effect of PDT in immunotherapy-treated CRC patients, with the MSI and POLE-mutation status as predictors of survival benefits.
Advances in CAR-NK cell therapy for hematological malignancies
Authors: Yang Rui , Yang Yun , Liu Rui , Wang Yiwen , Yang Ruoyu , He Aili
Published: June 2024

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of hematological malignancies, demonstrably improving patient outcomes and prognosis. However, its application has introduced new challenges, such as safety concerns, off-target toxicities, and significant costs. Natural killer (NK) cells are crucial components of the innate immune system, capable of eliminating tumor cells without prior exposure to specific antigens or pre-activation. This inherent advantage complements the limitations of T cells, making CAR-NK cell therapy a promising avenue for hematological tumor immunotherapy. In recent years, preclinical and clinical studies have yielded preliminary evidence supporting the safety and efficacy of CAR-NK cell therapy in hematological malignancies, paving the way for future advancements in immunotherapy. This review aims to succinctly discuss the characteristics, significant therapeutic progress, and potential challenges associated with CAR-NK cell therapy.
Integrating machine learning algorithms and multiple immunohistochemistry validation to unveil novel diagnostic markers based on costimulatory molecules for predicting immune microenvironment status in triple-negative breast cancer
Authors: Zhang Chao , Zhai Wenyu , Ma Yuyu , Wu Minqing , Cai Qiaoting , Huang Jiajia , Zhou Zhihuan , Duan Fangfang
Published: June 2024

Introduction

Costimulatory molecules are putative novel targets or potential additions to current available immunotherapy, but their expression patterns and clinical value in triple-negative breast cancer (TNBC) are to be clarified.

Methods

The gene expression profiles datasets of TNBC patients were obtained from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Diagnostic biomarkers for stratifying individualized tumor immune microenvironment (TIME) were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms. Additionally, we explored their associations with response to immunotherapy via the multiplex immunohistochemistry (mIHC).

Results

A total of 60 costimulatory molecule genes (CMGs) were obtained, and we determined two different TIME subclasses (“hot” and “cold”) through the K-means clustering method. The “hot” tumors presented a higher infiltration of activated immune cells, i.e., CD4 memory-activated T cells, resting NK cells, M1 macrophages, and CD8 T cells, thereby enriched in the B cell and T cell receptor signaling pathways. LASSO and SVM-RFE algorithms identified three CMGs (CD86, TNFRSF17 and TNFRSF1B) as diagnostic biomarkers. Following, a novel diagnostic nomogram was constructed for predicting individualized TIME status and was validated with good predictive accuracy in TCGA, GSE76250 and GSE58812 databases. Further mIHC conformed that TNBC patients with high CD86, TNFRSF17 and TNFRSF1B levels tended to respond to immunotherapy.

Conclusion

This study supplemented evidence about the value of CMGs in TNBC. In addition, CD86, TNFRSF17 and TNFRSF1B were found as potential biomarkers, significantly promoting TNBC patient selection for immunotherapeutic guidance.
MicroRNA-mediated metabolic regulation of immune cells in cancer: an updated review
Authors: Khameneh Sepideh Chowdary , Razi Sara , Lashanizadegan Ramin , Akbari Sanaz , Sayaf Masoud , Haghani Karimeh , Bakhtiyari Salar
Published: June 2024

The study of immunometabolism, which examines how immune cells regulate their metabolism to maintain optimal performance, has become an important area of focus in cancer immunology. Recent advancements in this field have highlighted the intricate connection between metabolism and immune cell function, emphasizing the need for further research. MicroRNAs (miRNAs) have gained attention for their ability to post-transcriptionally regulate gene expression and impact various biological processes, including immune function and cancer progression. While the role of miRNAs in immunometabolism is still being explored, recent studies have demonstrated their significant influence on the metabolic activity of immune cells, such as macrophages, T cells, B cells, and dendritic cells, particularly in cancer contexts. Disrupted immune cell metabolism is a hallmark of cancer progression, and miRNAs have been linked to this process. Understanding the precise impact of miRNAs on immune cell metabolism in cancer is essential for the development of immunotherapeutic approaches. Targeting miRNAs may hold potential for creating groundbreaking cancer immunotherapies to reshape the tumor environment and improve treatment outcomes. In summary, the recognition of miRNAs as key regulators of immune cell metabolism across various cancers offers promising potential for refining cancer immunotherapies. Further investigation into how miRNAs affect immune cell metabolism could identify novel therapeutic targets and lead to the development of innovative cancer immunotherapies.
Global trend and hotspot of resin materials for dental caries repair: a bibliometric analysis
Authors: Han Baodi , Wang Lian
Published: June 2024

Objective

The objective of this study is to explore the current research status, key areas, and future development trends in the field of resin materials for dental caries repair through an objective and quantitative analysis of the literature.

Methods

A search was conducted on the Web of Science Core Collection using “dental cavity” and “resin” as keywords, covering the period from 2000 to 2023. Data including author names, journals, countries, institutions, keywords, and citation rates were extracted. The collected data was subjected to statistical analysis using bibliometrics methodology, and visual knowledge maps were generated using software like CiteSpace 6.2.R4, Microsoft365, and R.

Results

A total of 4800 articles were retrieved, involving 13,423 authors, 2654 institutions, 76 countries, and 560 journals. The number of publications and cumulative publications in this field showed an increasing trend, reaching a peak in 2022. Dental Materials was the journal with the highest number of publications, cumulative publications, and citation rates. XU HHK was the most prolific author in terms of publications and citations. The University of Maryland was the institution with the highest number of publications. Brazil was the country with the highest number of publications. The USA had the highest level of collaboration with other countries. Collaboration between different authors, institutions, and countries in this field was relatively close, which contributed to the rapid development of resin materials for caries repair. The current research focus is mainly on the nature of dental caries, characteristics of resin materials, and bonding strength of adhesives. Enhancing the bioactivity and remineralization of resin materials, advanced antibacterial strategies, longevity and durability of resin restorations, nanotechnology, and material innovation, as well as digital dentistry, will receive increased attention as future research trends.

Conclusion

Resin materials for dental caries repair have received significant attention. Future research should combine nanotechnology and big data analysis to investigate the mechanisms of dental caries occurrence and development, enhance the performance and longevity of resin materials, and conduct high-quality, large-scale empirical research.
Visual and refractive outcomes of opposite clear corneal incision combined with rotationally asymmetric multifocal intraocular lens implantation
Authors: Qin Xiaoyu , Yao Pengxiang , Wu Xinyuan , Wu Yang , Hong Yufang , Chen Zhenzong , Yuan Yuanzhi
Published: June 2024

Purpose

To evaluate the visual and refractive outcomes of astigmatic cataract patients following opposite clear corneal incision (OCCI) combined with rotationally asymmetric multifocal intraocular lens (IOL) implantation.

Setting

Department of Ophthalmology, Zhongshan Hospital (Xiamen), Fudan University, People’s Republic of China.

Design

Retrospective cohort study.

Methods

This study comprised 58 cataract eyes of 54 patients with corneal astigmatism who underwent phacoemulsification and rotationally asymmetric multifocal IOL implantation which received either OCCI (OCCI group) or a single clear corneal incision (SCCI group). The follow-up period was 3 months after surgery. Distance, intermediate and near visual acuity, refractive outcomes, and corneal anterior keratometry were compared between the two groups. Vector analysis was used to evaluate astigmatism correction.

Results

Three months after surgery, the distance, intermediate and near visual acuity, and sphere remained comparable between the two groups, but a significant difference was detected in residual astigmatism and anterior corneal keratometric astigmatism. In the OCCI group, the residual astigmatism and keratometric astigmatism were −0.60 ± 0.29 D and 0.59 ± 0.28 D, respectively, which were lower than those in SCCI groups (−1.18 ± 0.47 D and 1.15 ± 0.45 D, both p < 0.05). In vector analysis, the difference vector (DV), angle of error (AoE), absolute AoE, index of success (IoS) and correction index (CI) were statistically significantly different between the two groups (p < 0.05).

Conclusion

OCCI combined with rotationally asymmetric multifocal intraocular lens implantation showed predictable and desirable efficacy in treating cataract patients with astigmatism.
Comparative analysis of obstetric, perinatal, and neurodevelopmental outcomes following chorionic villus sampling and amniocentesis
Authors: Kim Nari , Joo Eun Hui , Kim Seoyeon , Kim Taeho , Ahn Eun Hee , Jung Sang Hee , Ryu Hyun Mee , Lee Ji Yeon
Published: June 2024

Background

The risks of invasive prenatal tests are reported in previous studies such as miscarriage, fetal anomalies, and bleeding. However, few compare short-term and long-term outcomes between invasive tests. This study aims to investigate obstetric, perinatal, and children’s neurodevelopmental outcomes following chorionic villus sampling (CVS) or amniocentesis in singleton pregnancy.

Methods

This retrospective cohort study included healthy singleton pregnancies underwent transabdominal CVS (gestational age [GA] at 10–13 weeks) or amniocentesis (GA at 15–21 weeks) at a single medical center between 2012 and 2022. Only cases with normal genetic results were eligible. Short-term and long-term neurodevelopmental outcomes were evaluated.

Results

The study included 200 CVS cases and 498 amniocentesis cases. No significant differences were found in body mass index, parities, previous preterm birth, conception method, and cervical length (CL) before an invasive test between the groups. Rates of preterm labor, preterm premature rupture of the membranes, preterm birth, neonatal survival, neonatal short-term morbidities, and long-term neurodevelopmental delay were similar. However, the CVS group had a higher rate of cervical cerclage due to short CL before 24 weeks (7.0%) compared to the amniocentesis group (2.4%). CVS markedly increased the risk of cervical cerclage due to short CL (adjusted odd ratio [aOR] = 3.17, 95%CI [1.23–8.12], p = 0.016), after considering maternal characteristics.

Conclusion

Performing CVS resulted in a higher incidence of cerclage due to short cervix or cervical dilatation compared to amniocentesis in singleton pregnancies. This highlights the importance of cautious selection for CVS and the necessity of informing women about the associated risks beforehand.
A novel Enterococcus faecium phage EF-M80: unveiling the effects of hydrogel-encapsulated phage on wound infection healing
Authors: Khazani Asforooshani Mahshid , Elikaei Ameneh , Abed Sahar , Shafiei Morvarid , Barzi Seyed Mahmoud , Solgi Hamid , Badmasti Farzad , Sohrabi Aria
Published: June 2024

Background

Enterococcus faecium is one of the members of ESKAPE pathogens. Due to its resistance to antimicrobial agents, treating this bacterium has become challenging. The development of innovative approaches to combat antibiotic resistance is necessary. Phage therapy has emerged as a promising method for curing antibiotic-resistant bacteria.

Methods

In this study, E. faecium phages were isolated from wastewater. Phage properties were characterized through in vitro assays (e.g. morphological studies, and physicochemical properties). In addition, whole genome sequencing was performed. A hydrogel-based encapsulated phage was obtained and its structure characteristics were evaluated. Wound healing activity of the hydrogel-based phage was assessed in a wound mice model.

Results

The purified phage showed remarkable properties including broad host range, tolerance to high temperature and pH and biofilm degradation feature as a stable and reliable therapeutic agent. Whole genome sequencing revealed that the genome of the EF-M80 phage had a length of 40,434 bp and harbored 65 open reading frames (ORFs) with a GC content of 34.9% (GenBank accession number is OR767211). Hydrogel-based encapsulated phage represented an optimized structure. Phage-loaded hydrogel-treated mice showed that the counting of neutrophils, fibroblasts, blood vessels, hair follicles and percentage of collagen growth were in favor of the wound healing process in the mice model.

Conclusion

These findings collectively suggest the promising capability of this phage-based therapeutic strategy for the treatment of infections associated with the antibiotic-resistant E. faecium. In the near future, we hope to expect the presence of bacteriophages in the list of antibacterial compounds used in the clinical settings.
Immunotherapy in melanoma: advances, pitfalls, and future perspectives
Authors: Sorino Cristina , Iezzi Simona , Ciuffreda Ludovica , Falcone Italia
Published: June 2024

Cutaneous melanoma is the deadliest and most aggressive form of skin cancer owing to its high capacity for metastasis. Over the past few decades, the management of this type of malignancy has undergone a significant revolution with the advent of both targeted therapies and immunotherapy, which have greatly improved patient quality of life and survival. Nevertheless, the response rates are still unsatisfactory for the presence of side effects and development of resistance mechanisms. In this context, tumor microenvironment has emerged as a factor affecting the responsiveness and efficacy of immunotherapy, and the study of its interplay with the immune system has offered new promising clinical strategies. This review provides a brief overview of the currently available immunotherapeutic strategies for melanoma treatment by analyzing both the positive aspects and those that require further improvement. Indeed, a better understanding of the mechanisms involved in the immune evasion of melanoma cells, with particular attention on the role of the tumor microenvironment, could provide the basis for improving current therapies and identifying new predictive biomarkers.
Role of plasminogen activated inhibitor-1 in the pathogenesis of anticoagulant related nephropathy
Authors: Medipally Ajay , Xiao Min , Biederman Laura , Dasgupta Alana , Satoskar Anjali A. , Parikh Samir , Ivanov Iouri , Mikhalina Galina , Brodsky Sergey V.
Published: June 2024

Anticoagulant related nephropathy (ARN) is the result of glomerular hemorrhage in patients on systemic anticoagulation therapy or underlying coagulopathy. Red blood cells (RBC) that passed through the glomerular filtration barrier form RBC casts in the tubules, increase oxidative stress and result in acute tubular necrosis (ATN). The mechanisms of ARN still not completely discovered. Plasminogen activator inhibitor-1 (PAI-1) plays a significant role in the maintenance of coagulation homeostasis. We developed an animal model to study ARN in 5/6 nephrectomy (5/6NE) rats. The aim of this study was to elucidate the role of PAI-1 in the ARN pathogenesis. 5/6NE rats were treated per os with warfarin (0.75 mg/kg/day) or dabigatran (150 mg/kg/day) alone or in combination with PAI-1 antagonist TM5441 (2.5, 5.0 and 10 mg/kg/day). TM5441 in a dose dependent manner ameliorated anticoagulant-induced increase in serum creatinine in 5/6NE rats. Anticoagulant-associated increase in hematuria was no affected by TM5441. The levels of reactive oxygen species (ROS) in the kidneys were in a dose-dependent manner decreased in 5/6NE rats treated with an anticoagulant and TM5441. Our data demonstrates that PAI-1 may reduce ARN by decreasing ROS in the kidneys. Glomerular hemorrhage is not affected by anti-PAI-1 treatment. These findings indicate that while symptoms of ARN can be reduced by PAI-1 inhibition, the main pathogenesis of ARN – glomerular hemorrhage – cannot be prevented.