bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengembangan Game Edukasi Pengenalan Kosakata Bagi Siswa Penyandang Tunarungu di Sekolah Luar Biasa (SLB) Negeri Kanatang
Authors: Kornelis Vanesa Widia Ayusi , Pekuwali Arini Aha , Sitaniapessy Desy Asnath
Published: January 2025

Pendidikan merupakan hak fundamental bagi setiap individu, termasuk anak-anak dengan kebutuhan khusus seperti siswa Tunarungu di Sekolah Luar Biasa (SLB) Negeri Kanatang, Sumba Timur. Tantangan utama di sekolah ini adalah keterbatasan kosakata siswa tunarungu yang menghambat kemampuan mereka dalam berbahasa dan berkomunikasi. Penelitian ini difokuskan pada pengembangan game edukasi berbasis android dengan menggunakan metode Game Development Life Cycle (GDLC) dan Algoritma Fisher Yates Shuffle untuk mengacak latihan soal. Melalui pendekatan multimedia interaktif, game ini diharapkan dapat memperkaya pengalaman belajar siswa, memfasilitasi pemahaman kosakata serta meningkatkan inklusi pendidikan. Kontribusi penelitian ini terletak pada pengembangan teknologi pembelajaran inklusif di Indonesia untuk mengatasi kesenjangan akses dan mendukung kebutuhan pendidikan khusus. Dengan demikian, penelitian ini tidak hanya meningkatkan kualitas pembelajaran di SLB Negeri Kanatang, tetapi juga memperluas cakupan pendidikan yang setara bagi semua anak termasuk mereka yang menghadapi tantangan pendengaran. Pengujian aplikasi menggunakan metode Black Box Testing dan mendapatkan hasil bahwa fitur-fitur yang ada pada game edukasi yang dibangun telah sesuai dengan hasil yang diharapkan. Begitu juga dengan pengujian dengan menggunakan System Usability Scale  (SUS), perhitungan yang dilakukan mendapatkan hasil skor rata-rata sebesar 84,25 sehingga aplikasi yang sudah dibangun ini sudah sangat baik dan layak digunakan. Berdasarkan penelitian kepada siswa berjumlah 10 siswa didapatkan game edukasi pengenalan kosakata ini mampu menaikkan nilai siswa Penyandang Tunarungu di Sekolah Luar Biasa (SLB)  Negeri Kanatang sebesar 17% dengan nilai rata-rata post-test adalah 88.
Pendampingan Pengembangan Komponen Instrument Terpadu (KIT) Fisika Terbang untuk SMK Penerbangan
Authors: Arifin Mufti , Yuniarti Endah , Fairuza Syarifah
Published: January 2025

Keterbatasan fasilitas laboratorium fisika yang memadai dalam pelaksanaan praktikum fisika terbang di SMK Penerbangan merupakan salah satu hambatan dalam proses pembelajaran. Karena keterbatasan ini, pemahaman siswa terhadap konsep-konsep fisika yang mendasari prinsip-prinsip penerbangan menjadi kurang optimal. Untuk mengatasi permasalahan ini, kegiatan pengabdian masyarakat difokuskan pada peningkatan kapasitas guru SMK Penerbangan Gutama dalam merancang dan melaksanakan praktikum fisika. Melalui pembuatan dan pemanfaatan Komponen Instrumen Terpadu (KIT) fisika terbang, diharapkan guru dapat memberikan pengalaman belajar yang lebih konkret dan menarik bagi siswa. Dengan adanya 5 KIT yang telah berhasil dikembangkan, guru-guru kini memiliki bekal keterampilan untuk merancang kegiatan praktikum yang variatif dan sesuai dengan kebutuhan pembelajaran. Selain itu, pendampingan yang diberikan juga telah membekali guru dengan pengetahuan mendalam tentang konsep-konsep fisika yang relevan dengan dunia penerbangan. Diharapkan, keberhasilan kegiatan ini dapat meningkatkan kualitas pembelajaran fisika di SMK Penerbangan Gutama, mendorong semangat inovasi guru dalam mengembangkan lebih banyak KIT, serta mempersiapkan lulusan yang lebih kompeten di bidang penerbangan.
KUAT TEKAN BETON DENGAN PENAMBAHAN SERBUK BESI DAN BAJA
Authors: Paryati Ninik
Published: January 2025

Di Indonesia, serbuk besi dan baja hasil kegiatan penggergajian besi dan baja jarang dimanfaatkan, sehingga menyebabkan pencemaran lingkungan. Dalam penelitian yang dilakukan Ninik Paryati pada tahun 2001, serbuk besi dan baja digunakan sebagai bahan tambah dalam pembuatan beton sebagai usaha pemecahan masalah limbah tersebut, dengan cara meneliti seberapa jauh pemanfaatan limbah berupa serbuk besi dan baja dapat digunakan sebagai bahan tambah dalam campuran beton dengan presentase 0%, 25%, 50%, 75% ditinjau dari kuat tekannya. Penelitian ini menggunakan metode eksperimen dengan benda uji berupa kubus 15cmx15cmx15cm yang ditekan pada umur 28 hari. Setiap variasi penambahan berjumlah 6 benda uji dengan perbandingan berat antara semen : agregat halus : agregat kasar adalah 1: 3 : 5, sehingga keseluruhan benda uji berjumlah 24 buah. Hasil penelitian menunjukkan bahwa kuat tekan karakteristik beton pada variasi penambahan 0%, serbuk besi dan baja σk = 125,4894 kg/cm2, 25% serbuk besi dan baja σk = 121,9823 kg/cm2,50% serbuk besi dan baja σk = 118,063 kg/cm2, 75% serbuk besi dan baja σk = 80,3928 kg/cm2.Hasil tersebut menunjukkan bahwa semakin besar penambahan, maka kuat tekan beton yang dicapai semakin menurun. Hal ini disebabkan karena beberapa faktor, antara lainadalah adanya kesalahan pemilihan permukaan yang ditekan, adanya korosi antar butir, adanya segregasi dan timbulnya gelembung air serta proses pencampuran baha-bahan penyusun beton yang tidak sempurna.
Kata Kunci : KUAT TEKAN BETON, BESI, BAJA
THE UNIVERSAL LAW OF CATALYSIS
Authors: Kaplunenko Volodymyr , Kosinov Mykola
Published: January 2025

The general sign and general mechanism of catalytic reactions based on the transfer of electric charges to reagents has been revealed. This mechanism of catalysis is realized on the fundamental level - on the level of interaction of elementary particles (electrons and protons). The choice of this mechanism of catalysis made it possible to obtain the general law of catalysis and private laws for other types of catalysis. The main parameter in the equation of the generalized law of catalysis is the total electric charge obtained by the reactants. In catalysis, the donor-acceptor mechanism is realized, which leads to a change in the oxidation state of the reactants and to a decrease in the activation energy of the chemical reaction. The main active factor in the donor-acceptor mechanism of catalysis is the electrical charge that transfers the catalyst to the reactants. The electric charge is a quantitative characteristic in the formula for the universal law of catalysis. From the universal law of catalysis, the laws of heterogeneous, homogeneous, combined, field catalysis, and Faraday's law of electrolysis follow as private results.
A New Explanation for the Result of Michelson-Morley Experiment
Authors: Soltani Abolfazl
Published: January 2025

The result of Michelson-Morley observations, namely non-displacement of interference fringes after 90 degrees rotation of interferometer, was explained by various theories like Einstein’s theory, namely the theory of independence of light velocity from observer velocity and source velocity without necessity of the presence of Luminiferous Aether. However, it seems that, apart from these theories, there is another way to explain Michelson-Morley null observations. In this article we propose the theory of "Aether Attached to Earth" or abbreviated AATE. In this theory Luminiferous Aether is a fact and is a transparent continuous medium that has filled the entire universe and is attached and is locked to the center of Earth and whole of it, just like an integrated rigid object, is moved along with Earth in Space. It’s clear, in AATE theory, the velocity of Earth relative to Aether is zero; Therefore, the null displacement of the fringes can be explained. Here you will see that the AATE theory does not experience the failures of previous Aether theories.
Manajemen Perencanaan Tata Ruang Perpustakaan Widya Pustaka Sebagai Upaya Mendukung Pengembangan Budaya Literasi SMP Negeri 3 Bantul
Authors: Hariyanto Subekti , Rusandi La Ode
Published: January 2025

Penelitian ini bertujuan untuk menganalisis kondisi tata ruang Perpustakaan Widya Pustaka SMP Negeri 3 Bantul dan merumuskan upaya peningkatan tata ruang dalam mendukung pengembangan budaya literasi di sekolah. Penelitian ini menggunakan pendekatan deskriptif kualitatif dengan teknik pengumpulan data melalui observasi, wawancara, dan studi dokumentasi. Hasil penelitian menunjukkan bahwa tata ruang Perpustakaan Widya Pustaka saat ini belum optimal, dengan permasalahan utama meliputi penataan ruang yang kurang efisien, minimnya area fungsional yang mendukung kegiatan literasi, kurangnya aspek estetika dan dekorasi, serta pencahayaan dan sirkulasi udara yang kurang memadai. Upaya peningkatan tata ruang yang direkomendasikan meliputi penataan ulang area fungsional, optimalisasi perabot dan furnitur, peningkatan aspek estetika dan dekorasi, perbaikan sistem pencahayaan dan sirkulasi udara, serta pengadaan area-area baru yang mendukung kegiatan literasi. Manajemen perencanaan tata ruang perpustakaan yang baik, dengan memperhatikan prinsip-prinsip penataan ruang perpustakaan, dapat menciptakan lingkungan yang nyaman, efisien, dan mendukung pengembangan budaya literasi di SMP Negeri 3 Bantul.
Whole-genome analysis of a ST45-SCCmec IVa (2B)-t116 methicillin-resistant Staphylococcus aureus strain isolated from the sputum of a 5-year-old child with pneumonia
Authors: Huang Lin , Guo Rui , Lin Jingxian , Li Xiaowei , Li Zhicong , Zhang Limei , Li Wenting , Xue Rui , Zhang Cheng , Feng Xiaosan , Li Xiaobin
Published: January 2025

Introduction

Methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 45 is a major global MRSA lineage with huge strain diversity and a high clinical impact. In Hainan and Guangzhou of China, the ST45-MRSA was mainly associated with t116.

Methods

The MRSA strain SA2107 was isolated from the sputum of a 5-year-old child with pneumonia. The whole genome of SA2107 was sequence using Illumina (Novaseq 6000) and PacBio (Sequel IIe) sequencers, and the sequences were assembled using hybrid assembly. The carriage of antibiotic resistance genes, virulence genes, and mobile genetic elements were identified using bioinformatics tools. The comparative genomic analyses of MRSA strain SA2107 with other MRSA strains worldwide were performed.

Findings

The genome size of ST45-SCCmec IVa (2B)-t116 MRSA strain SA2107 was ~2.9 Mb. Mobile genetic elements analysis of SA2107 revealed two plasmids (30,064-bp pSA2107-1 and 8,033-bp pSA2107-2), three prophages, two integrative and conjugative elements (ICEs), and two insertion sequences (ISs, IS431 and IS1272). The SCCmec IVa (2B) carried by SA2107 contained the class B mec gene complex (IS431-mecA-ΔmecR1-IS1272) and type 2 ccr gene complex (ccrA2 and ccrB2). Besides mecA, another beta-lactam resistance gene blaZ was found to located on six copies of bla complex (blaZ, blaR1, and blaI) on the chromosome of SA2107. Three kinds of virulence factors were detected on the chromosome of SA2107, including genes encoding toxins, exoenzyme, and immune-modulating protein. Notably, the three prophages harbored by the chromosome of SA2107 all carried virulence genes.

Conclusion

Thus far, only three complete genomes available for ST45-SCCmec IVa (2B)-t116 strain from United States, Germany, and Australia, respectively. The strain SA2107 was the first complete genome data (CP104559) from China for ST45-SCCmec IVa (2B)-t116 MRSA.
A mouse model of immunosuppression facilitates oral Candida albicans biofilms, bacterial dysbiosis and dissemination of infection
Authors: Veerapandian Raja , Paudyal Anuja , Schneider Sarah M. , Lee Sonny T. M. , Vediyappan Govindsamy
Published: January 2025

Opportunistic pathogens are a major threat to people, especially those with impaired immune systems. Two of the most important microbes in this category are the fungus Candida albicans and Gram-positive bacteria of the genus Enterococcus, which share overlapping niches in the oral cavity, gastrointestinal and urogenital tracts. The clinical importance of oral C. albicans biofilm and its interaction with the host under immunosuppressive conditions remains largely understudied. Here, we used a mouse model of oropharyngeal candidiasis (OPC) with cortisone acetate injection on alternate days and a continuous supply of C. albicans in drinking water for three days, resulting in immunosuppression. Results showed abundant growth of resident oral bacteria and a strong C. albicans biofilm on the tongue consisting of hyphae which damaged papillae, the epidermal layer, and invaded tongue tissue with the accumulation of inflammatory cells as demonstrated by Grocott’s methenamine silver and hematoxylin and eosin staining, respectively. The dispersed microbes from the oral biofilm colonized the gastrointestinal (GI) tract and damaged its integrity, disseminating microbes to other organs. Although no visible damage was observed in the kidney and liver, except increased lipid vacuoles in the liver cells, C. albicans was found in the liver homogenate. Intriguingly, we found co-occurrence of Enterococcus faecalis in the tongue, liver, and stool of immunosuppressed control and C. albicans infected organs. Targeted 16S rRNA and ITS2 amplicon sequencing of microbes from the fecal samples of mice confirmed the above results in the stool samples and revealed an inverse correlation of beneficial microbes in the dysbiosis condition. Our study shows that mucosal-oral infection of C. albicans under immunosuppressed conditions causes tissue damage and invasion in local and distant organs; the invasion may be aided by the overgrowth of the resident endogenous Enterobacteriaceae and other members, including the opportunistic pathogen Enterococcus faecalis.
Identifying etiologies of heart failure using non-contrast cardiac magnetic resonance imaging: cine imaging, T1 and T2 mapping, and texture analysis for T1 mapping
Authors: Amano Yasuo , Suzuki Yasuyuki , Tang Xiaoyan , Ando Chisato
Published: January 2025

Objective

The aim of this retrospective study was to evaluate the usefulness of non-contrast cardiac magnetic resonance imaging, including cine imaging, T1 and T2 mapping, and texture analysis for T1 mapping, for identifying etiologies of heart failure (HF).

Methods

Forty-seven patients with HF were examined using a 1.5 T scanner. Cine imaging parameters and native T1 and T2 values at the mid-septal segment were measured. Vertical run length nonuniformity, vertical gray level nonuniformity (vGLNU), wavelet energy LL(3) and HH (4) on T1 mapping were estimated at the mid-septal segment using open-access software. Late gadolinium enhancement was investigated to help diagnose the etiologies of HF. We used Kruscal-Wallis’ with a post-hoc Steel-Dwass' test, Wilcoxon signed-ranked test, Pearson's chai square test and receiver operator curve analysis (ROC) to assess the usefulness of non-contrast CMR for identifying etiologies of HF.

Results

There were significant differences in left ventricular end-diastolic volume (LVEDV) indexed to body surface area (LVEDVi), left ventricular myocardial mass/LVEDV, native T1, and vGLNU between dilated cardiomyopathy (DCM), hypertensive cardiomyopathy (HC) and tachycardia-induced cardiomyopathies (TIC). DCM had higher T1 and lower vGLNU than HC. When compared with TIC, DCM showed significantly higher LVEDV and LVEDVi. ROC analysis revealed that LVEDV and vGLNU provided high specificity for differentiating DCM from the other etiologies.

Conclusion

Native T1 mapping and its texture analysis may be valuable for differentiating between DCM and HC. Cine imaging can be useful for differentiating between DCM and TIC.
Association between cardiopulmonary bypass duration and early major adverse cardiovascular events after surgical repair of supravalvular aortic stenosis
Authors: Zhang Simeng , Wei Caiyi , Peng Bo , Lv Lizhi , Pei Fengbo , Xia Jianming , Yan Jun , Liu Jie , Wang Qiang , Shi Yi
Published: January 2025

Background

Patients who underwent surgical repair of supravalvular aortic stenosis (SVAS) are at high risk for postoperative major adverse cardiovascular events (MACE). This study aimed to investigate the association between cardiopulmonary bypass (CPB) duration and MACE occurring during postoperative hospitalization or within 30 days post-surgery.

Methods

Patients who underwent surgical repair of SVAS from 2002 to 2019 at Beijing Fuwai Hospital and Yunnan Fuwai Hospital were included in this study. Patients were stratified into “CPB duration >2 h” and “CPB duration ≤2 h” groups based on intraoperative CPB duration. Various statistical methodologies were employed to investigate the association between CPB duration and early postoperative MACE, including multivariate adjustment, propensity score adjustment, propensity score matching, and logistic regression based on propensity score weighting.

Results

297 participants were included and 164 were finally matched. In the propensity score-matched cohort, CPB duration was positively associated with early postoperative MACE (odds ratio = 18.13; 95% confidence interval 2.33–140.86; P = 0.006). Consistent results were obtained in the Inverse probability of treatment-weighted, standardized mortality ratio-weighted, pairwise algorithmic-weighted, and overlap-weighted models.

Conclusion

Patients with CPB duration >2 h were at a higher risk of early postoperative MACE compared to those with CPB duration ≤2 h. This emphasized the significance of minimizing CPB exposure for the prognosis of patients with SVAS.
ChestX-Transcribe: a multimodal transformer for automated radiology report generation from chest x-rays
Authors: Singh Prateek , Singh Sudhakar
Published: January 2025

Radiology departments are under increasing pressure to meet the demand for timely and accurate diagnostics, especially with chest x-rays, a key modality for pulmonary condition assessment. Producing comprehensive and accurate radiological reports is a time-consuming process prone to errors, particularly in high-volume clinical environments. Automated report generation plays a crucial role in alleviating radiologists' workload, improving diagnostic accuracy, and ensuring consistency. This paper introduces ChestX-Transcribe, a multimodal transformer model that combines the Swin Transformer for extracting high-resolution visual features with DistilGPT for generating clinically relevant, semantically rich medical reports. Trained on the Indiana University Chest x-ray dataset, ChestX-Transcribe demonstrates state-of-the-art performance across BLEU, ROUGE, and METEOR metrics, outperforming prior models in producing clinically meaningful reports. However, the reliance on the Indiana University dataset introduces potential limitations, including selection bias, as the dataset is collected from specific hospitals within the Indiana Network for Patient Care. This may result in underrepresentation of certain demographics or conditions not prevalent in those healthcare settings, potentially skewing model predictions when applied to more diverse populations or different clinical environments. Additionally, the ethical implications of handling sensitive medical data, including patient privacy and data security, are considered. Despite these challenges, ChestX-Transcribe shows promising potential for enhancing real-world radiology workflows by automating the creation of medical reports, reducing diagnostic errors, and improving efficiency. The findings highlight the transformative potential of multimodal transformers in healthcare, with future work focusing on improving model generalizability and optimizing clinical integration.
Assessment of root resorption on lateral incisors after primary canine extraction treating mesioangular displaced permanent canines: a randomised controlled trial
Authors: Helal Narmin , Naaman Reem , Alamoudi Najlaa , El-Housseiny Azza , Jadu Fatima
Published: January 2025

Aim

Root resorption (RR) of the adjacent maxillary lateral incisors is considered the most common complication of displaced maxillary canines. The aim of this study was to assess the effect of interceptive extraction of the primary canines on the condition of the roots of permanent neighbouring teeth to mesioangular displaced canines (MDC). In addition, this study aimed to investigate the relationship between the position of the unerupted canine and the risk of RR in adjacent lateral incisors.

Design

Randomised controlled clinical trial.

Methods

Eighty-five patients 9–12-year-old with MDC were allocated equally to either an extraction group (EG) or a control group (CG). Of the sample, 33 were males (38.8%), and 52 were females (61.2%). Among this sample, 81 canines (51.9%) were buccally displaced, 34 canines (21.8%) were palatally displaced, and 41 canines (26.3%) were mid-alveolar. All subjects underwent cone-beam computed tomography examination to determine the presence, stage, and level of lateral incisor root resorption (RR). Measurements were performed at T0 and repeated at a 12-month follow-up (T2).

Results & statistics

Root resorption (RR) was present in 28.2% of lateral incisors at the baseline assessment (T0) and exhibited a significant increase at the 12-month follow-up (T12). This marked increase in resorption severity was evident between T0 and T12 (P = 0007), regardless of group allocation. There was a significant increase in the degree of resorption between T2 and T0, with a mean difference equals to 0.31 (0.73), P < 0.0001. While there was no statistically significant difference in resorption levels between the extraction and control groups at T0 (P = 0.11), RR occurred more frequently with midalveolar (34.1%) and palatal (32.3%) displacements than with buccal displacements (23.5%). Severe resorption was observed more frequently in cases involving palatally displaced canines within both groups, but it did not reach statistical significance.

Conclusions

Lateral incisor root resorption (RR) progressed significantly within a 12-month period irrespective of treatment modality. RR occurred more frequently with midalveolar and palatal displacement with a trend towards increased RR severity in cases with palatally displaced canines. Early clinical evaluation and consistent monitoring is essential for early detection and potential intervention in patients with mesioangular canine displacement.
Diagnostic efficiency of exome-based sequencing in pediatric patients with epilepsy
Authors: Zou Huafang , Zhang Qian , Liao Jianxiang , Zou Dongfang , Hu Zhanqi , Li Bing , Chen Li , Wen Jialun , Zhao Xia , Zhang Victor Wei , Cao Dezhi
Published: January 2025

Objective

Epilepsy, a prevalent neurological disorder, has multifaceted etiologies. Next-generation sequencing (NGS) has emerged as a robust diagnostic tool for this condition. This study aims to evaluate the detection efficiencies of different exome-based sequencing techniques.

Methods

Exome-based epilepsy panel tests, clinical exome sequencing (CES), and whole exome sequencing (WES) were conducted on 259 pediatric patients diagnosed with epilepsy. Single-nucleotide variants (SNVs) and copy number variants (CNVs) were interpreted based on each patient’s phenotypic presentation. Additionally, data concerning clinical symptoms, neuroimaging findings, treatment responses, and prognostic outcomes were collected and analyzed.

Results

The overall diagnostic yield was 32.8% (85/259), with a diagnostic yield of 40.0% for exome-based epilepsy panels, 30.1% for CES, and 27.8% for WES. We identified 82 cases with pathogenic or likely pathogenic SNVs and 4 cases with pathogenic CNVs, of which one case with both SNV and CNV. The most frequently detected gene was PRRT2, present in 10.0% (9/82) of cases. Epileptic syndromes were diagnosed in 66 patients, predominantly West Syndrome, Dravet Syndrome and Genetic Epilepsy with Febrile Seizures plus.

Conclusion

NGS is an effective method for uncovering the genetic foundations of pediatric epilepsy, with diagnostic yields varying based on the sequencing approach used. The growing preference for WES underscores its utility in complex cases, pointing to a trend towards more tailored diagnostic strategies.
Revisiting the role of IL-27 in obesity-related metabolic diseases: safeguard or perturbation?
Authors: An Jinyang , Fu Donghua , Chen Ximei , Guan Conghui , Li Lingling , Bai Jia , Lv Haihong
Published: January 2025

The prevalence of metabolic diseases, such as obesity, has been steadily increasing in recent years, posing a significant threat to public health. Therefore, early identification and intervention play a crucial role. With the deepening understanding of the etiology of metabolic diseases, novel therapeutic targets are emerging for the treatment of obesity, lipid metabolism disorders, cardiovascular and cerebrovascular diseases, glucose metabolism disorders, and other related metabolic conditions. IL-27, as a multi-potent cytokine, holds great promise as a potential candidate target in this regard. This article provides a comprehensive review of the latest findings on IL-27 expression and signal transduction in the regulation of immune inflammatory cells, as well as its implications in obesity and other related metabolic diseases. Furthermore, it explores the potential of IL-27 as a novel therapeutic target for the treatment of obesity and metabolic disorders. Finally, an overview is presented on both the opportunities and challenges associated with targeting IL-27 for therapeutic interventions.
Islet organoids: a new hope for islet transplantation in diabetes
Authors: Yu Xuemei , Liu Chengkong , Kuang Zheng , Song Siyuan , Tian Limin , Wang Yi
Published: January 2025

Diabetes mellitus, including Type 1 diabetes (T1D) and advanced Type 2 diabetes (T2D), remains a major global health challenge due to the destruction or dysfunction of insulin-producing β-cells. Islet transplantation offers a promising therapeutic strategy. However, it is limited by organ shortage globally and other risk factors. Recent advancements in organoid technology provide transformative solutions for islet regeneration. This review summarized three groundbreaking approaches: islet organoids differentiated from Procr+ pancreatic progenitor cells, chemically induced pluripotent stem cells (CiPSCs), and endoderm stem cells (EnSCs). Procr+ cells exhibit multipotency and potential for in vivo activation, offering a scalable and non-invasive strategy for β-cell regeneration. CiPSCs, reprogrammed via small molecules, enable personalized islet therapies with promising clinical outcomes, as demonstrated in T1D patients. EnSC-derived islets (E-islets) offer high differentiation efficiency and therapeutic efficacy, particularly for T2D patients with residual β-cell function. While each approach addresses specific challenges in islet transplantation, further research is needed to optimize scalability, immune compatibility, and long-term functionality. This review highlights the potential of organoid-based technologies to revolutionize diabetes treatment and pave the way for personalized, curative therapies.
Construction of flame-retardant and water-resistant polybutylene terephthalate composites by reactive extrusion
Authors: Ran Guowen , Zhang Jingfan , Yuan Yihui , Xie Haisheng , Li Tao , Lan Xiucai , Cao Yanxiao
Published: January 2025

The combination of aluminum diethylphosphinate (ADP) and melamine pyrophosphate (MPP) has been extensively utilized in flame-retardant polybutylene terephthalate (PBT) composites. However, the hydrophilic nature of ADP and MPP leads to their migration to the surface or separation from the PBT matrix under the influence of heat and moisture, which subsequently results in the degradation of both flame retardancy and mechanical properties. In this study, reactive epoxy groups were introduced onto the surface of the flame retardant (FR) using a simple method. The resulting encapsulated flame retardant (EP@FR) was then incorporated into PBT via a twin-screw extruder. During extrusion process, the reactive epoxy groups interacted with the free terminal hydroxy and carboxy derived from the PBT, forming covalent bonds at the interface of FR and PBT, thereby enhancing flame retardancy and water resistance. With the addition of 16.0 wt% EP@FR, the PBT/EP@FR composites achieved a UL-94 V-0 rating with an LOI value of 28.5%. Notably, the mechanical properties and UL-94 V-0 rating of the PBT/EP@FR composites were maintained even after immersion in water at 70°C for 14 days. It is expected that this work can provide a promising strategy for the development of flame-retardant and water-resistant PBT composites.
Recommendations for the primary prevention of atherosclerotic cardiovascular disease in primary care: a systematic guideline review
Authors: Bredehorst Maren , González-González Ana I. , Schürmann Lara , Firmansyah Dennis , Muth Christiane , Haasenritter Jörg , van der Wardt Veronika , Puzhko Svetlana
Published: January 2025

Introduction

This study systematically reviews and synthesizes recommendations from national and international clinical practice guidelines (CPGs) regarding the primary prevention of atherosclerotic cardiovascular disease (ASCVD) in adults in primary care settings.

Methods

CPGs were retrieved from MEDLINE, Trip, guideline repositories, and websites of guidelines-producing societies. Two reviewers independently screened the guidelines for eligibility, assessed their quality, and extracted study characteristics and relevant recommendations for further consistency analysis. Recommendations, with their strength and evidence level, were thematically coded and clustered around clinical questions using ATLAS.ti.

Results

We included 26 CPGs from which we extracted 581 recommendations on risk assessment, non-pharmacological, and pharmacological interventions. Twenty-one guidelines (81%) were rated as having “very good” methodological quality. We categorized the recommendations into 124 clusters. Forty-four clusters (35%) included consistent recommendations, but only four of them (3%) included highly consistent recommendations. These clusters emphasized avoiding routine prescriptions of nicotinic acid, aspirin, and fibrates for primary ASCVD prevention alone, and recommending 20 mg/day of atorvastatin for high-risk ASCVD patients. The recommendations also highlighted the importance of adhering to a Mediterranean-type diet, patient-centered counseling, and standardized risk assessment for patients over the age of 40.

Discussion

This review underscores the heterogeneity in primary ASCVD prevention recommendations and the importance of personalized strategies for at-risk individuals.

Systematic review registration

PROSPERO, CRD42023394605, available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023394605.
Eosinophilic esophagitis in the “atopic march”: dupilumab as an “umbrella” strategy for multiple coexisting atopic diseases
Authors: Lutzu Nicola , Favale Agnese , Demurtas Mauro , Del Giacco Stefano , Onali Sara , Fantini Massimo Claudio
Published: January 2025

Dupilumab is a monoclonal antibody targeting interleukin-4 and interleukin-13, approved for the treatment of multiple T2 diseases and more recently for Eosinophilic Esophagitis (EoE). EoE is a chronic T2 inflammatory disease, believed to be a member of the “atopic march”, due to multiple similarities with other atopic diseases, ranging from epidemiology to genetics and pathophysiology. Although often co-existing in the same patient, these diseases are still treated as separated entities by different specialists, resulting in polypharmacy and chronic use of steroids. Thus, a shared-decision approach by a multidisciplinary team composed of different specialists might improve clinical management and outcomes. Yet, prospective data on the effectiveness of dupilumab as a single agent for multiple T2 inflammatory diseases are lacking, since only few case reports and small studies have been published so far reporting outcomes in patients affected by multiple T2 diseases. The purpose of this review is to illustrate the rationale and clinical evidence supporting the possibility of using dupilumab as a single therapeutic agent in those patients affected by multiple T2 diseases in addition to EoE.
Probiotic potential and safety properties of Limosilactobacillus fermentum A51 with high exopolysaccharide production
Authors: Wei Guangqiang , Wang Daodian , Wang Teng , Wang Gao , Chai Yunmei , Li Yufang , Mei Minhui , Wang Hao , Huang Aixiang
Published: January 2025

Introduction

Exopolysaccharides (EPS) produced by Lactic acid bacteria have many health benefits and unique physicochemical properties. They are widely used in the food industry to improve viscosity, mouthfeel, and textural properties of foods. In our previous studies, Limosilactobacillus fermentum A51 (L. fermentum A51) isolated from yak yogurt exhibited high EPS production capacity and was applied to improve the texture of yogurt. In this study, whole genome sequencing analysis and corresponding in vitro assays were performed to investigate the probiotic potential and safety properties of L. fermentum A51.

Results

Scanning electron microscopy (SEM) observed that L. fermentum strain A51 adhered into clusters and its colony exhibited the obvious silk drawing phenomenon. Whole genome mapping revealed that L. fermentum A51 genome is 2,188,538 bp, and with an average guanine and cytosine (GC) content of 51.28%. PGAAP annotation identified 2,152 protein-encoding genes and 58 rRNAs, 15 tRNAs, and 5 5sRNAs. Hemolysis and antibiotic resistance tests, combined with the analysis of genes involved in antibiotic resistance, virulence factor, and hemolysins, suggested that L. fermentum A51 is safe. Fifty-one carbohydrate active enzyme genes in the whole genome sequence of L. fermentum A51 were annotated by carbohydrate active enzymes (CAZymes). Furthermore, L. fermentum A51 possesses adhesion, acid tolerance, bile salt tolerance, and heat tolerance genes (srtA, tuf, Bsh, nhaC, Ntn, cfa), antioxidant (nrfA, npr, nox2, tps), antibacterial genes (Idh and Dld) EPS synthesis-related genes (glf, epsG, gtf, Wzz, Wzx, Wzy), and signal molecule A1-2 synthesis-related genes (luxS, pfs). These probiotic genes were verified by quantitative real-time PCR. In vitro assays confirmed that L. fermentum A51 showed good tolerance to simulated gastrointestinal tract (8.49 log CFU/mL), 0.3% bile salt (39.06%), and possessed adhesion (86.92%), antioxidant (70.60–89.71%), and antimicrobial activities, as well as EPS and signaling molecule AI-2 synthesis capacities.

Conclusion

Collectively, our findings have confirmed that L. fermentum A51 is safe and exhibits good probiotic properties, thus recommending its potential application in the production of value-added fermented dairy products.
Associations between cerebral blood flow and progression of white matter hyperintensities
Authors: Thammasart Siriluk , Harvey Danielle J. , Maillard Pauline , DeCarli Charles , Donnay Corinne A. , Wheeler Gregory J. , Fan Audrey P.
Published: January 2025

Introduction

In an aging population, white matter hyperintensities (WMHs), observed on FLAIR MRI sequences, are indicators of cognitive decline, motor impairment, and increased vascular risk. However, the pathophysiological mechanisms underlying WMHs, including dynamic changes in cerebral blood flow (CBF) within and adjacent to lesions, remain poorly understood.

Methods

Our study examined a diverse cohort of 300 elderly participants through arterial spin labeling (ASL) on 3 Tesla MRI, analyzing both cross-sectional and longitudinal data. We characterized the relationship between CBF and WMH development in different lesion locations (based on distance from ventricles) and brain tissue types (WMH lesion, penumbra, and normal white matter).

Results

Our findings reveal that WMHs exhibit significantly lower relative CBF (rCBF) compared to penumbra, normal-appearing white matter, and gray matter, with juxtaventricular WMHs (JVWMH) displaying the most substantial reductions. Longitudinally, WMHs that increased in size over a two-year period had lower baseline rCBF than those that remained stagnant, particularly in juxtaventricular and periventricular regions.

Discussion

This study not only highlights the predictive value of rCBF in WMH progression but also provides location-specific hemodynamic information about WMHs that can guide clinical management of WMH-related brain changes and their clinical manifestations.
Lateralized differences in power spectra across different frequency bands during NREM sleep in patients with primary insomnia
Authors: Huang Jiao , Ye Jing , Gao Mingjie , Gao Wentao , Chen Weijia , Zhu Yifeng , Wang Yongbo , Huang Daijin , Lv Yunhui , Shi Hong
Published: January 2025

Objective

To compare the electroencephalogram power spectrum of patients with primary insomnia and good sleep controls in multiple brain areas and different frequency bands during non-rapid eye movement sleep.

Methods

48 primary insomnias and 30 age-and gender-matched good sleep controls were recorded overnight with polysomnography. Power spectral analysis was performed in six brain areas (F3, F4, C3, C4, O1 and O2) and across seven frequency bands (delta, sigma, alpha, theta, beta1, beta2, and gamma) during non-rapid eye movement sleep between primary insomnias and good sleep controls.

Results

In primary insomnias, there were significant differences in frequency bands and areas. Compared to good sleep controls, delta power was lower in primary insomnias, while beta1, beta2, and gamma were higher. Beta2 power was substantially higher in all areas, sigma power was significantly higher on the right side, and gamma power was considerably higher on the left side in primary insomnias. The Beta1 power was positively correlated the number of awakenings (r = 0.3291, p = 0.02) in primary insomnias on the right side.

Conclusion

This study marked the first specialized comparison of power spectral analysis during non-rapid eye movement sleep in different areas and across different frequency bands. The result suggested that primary insomnias had reduced deep sleep (lower delta power) and hyperarousal state (higher beta 2 power). Primary insomnia was associated with significant fragmented sleep, and an increase in beta1 power was related to the number of awakenings.

Significance

These findings revealed the hemispheric lateralization characteristics of power spectral disturbances during non-rapid eye movement sleep in primary insomnias and provided valuable insights for selecting electrode placements in future power spectral analyses of primary insomnias.
Nicotinic α7 receptors on cholinergic neurons in the striatum mediate cocaine-reinforcement, but not food reward
Authors: Fritz Michael , Rosa Priscila Batista , Wilhelms Daniel , Jaarola Maarit , Ruud Johan , Engblom David , Klawonn Anna M.
Published: January 2025

The neurotransmitter acetylcholine has since long been implicated in reward learning and drug addiction. However, the role of specific cholinergic receptor subtypes on different neuronal populations remain elusive. Here, we studied the function of nicotinic acetylcholinergic alpha 7 receptors (α7 nAChRs) in cocaine and food-enforced behaviors. We found that global deletion of α7 nAChRs in mice attenuates cocaine seeking in a Pavlovian conditioned place preference paradigm and decreases operant responding to cocaine in a runway task and in self-administration, without influencing responding to palatable food. This effect can be attributed to alpha 7 receptor signaling in the striatum, as selective deletion of striatal α7 nAChRs using a viral vector approach resulted in a similar decrease in cocaine-preference as that of global deletion. To investigate which type of striatal neurons are responsible for this effect, we selectively targeted Cholinergic (ChAT-expressing) neurons and dopamine D1-receptor (D1R) expressing neurons. Mice with conditional deletion of α7 nAChRs in ChAT-neurons (α7 nAChR-ChATCre) exhibited decreased cocaine place preference and intact place preference for food, while α7 nAChR-D1RCre mice had no changes in reward learning to neither food nor cocaine. Cocaine induction of striatal immediate early gene expression of cFos, FosB, Arc and EGR2 was blocked in α7 nAChR-ChATCre mice, demonstrating the importance of α7 nAChRs on cholinergic neurons for striatal neuronal activity changes. Collectively, our findings show that α7 nAChRs on cholinergic interneurons in the striatum are pivotal for learning processes related to cocaine, but not food reward.
Associations of dietary inflammation index and composite dietary antioxidant index with all-cause mortality in COPD patients
Authors: Zhao Sue , Su Yingjie , Yang Hongzhong
Published: January 2025

Background

Few studies have investigated the effects of both dietary inflammatory index (DII) and composite dietary antioxidant index (CDAI) on mortality in patients with Chronic Obstructive Pulmonary Disease (COPD). Our research aimed to explore the associations between the two indicators with all-cause mortality in COPD patients.

Methods

We conducted a prospective cohort analysis based on data from the six cycles of the National Health and Nutrition Examination Survey (NHANES) dataset from 2007 to 2018. Multivariate Cox proportional hazard models were used to analyze the effects of DII and CDAI on all-cause mortality in COPD. We employed restricted cubic spline (RCS) analysis to examine the dose–response relationship between two indicators and all-cause mortality, used threshold effect analysis to determine the inflection point, and conducted subgroup analysis and interaction tests to verify the stability of the results.

Results

A total of 1,457 COPD patients aged over 40 were enrolled in the study. The median follow-up time was 76.8 months. The multivariate Cox proportional hazards model showed that increased DII was associated with an increase in all-cause mortality (HR (95% CI): 1.11(1.04, 1.18), p = 0.002). In contrast, CDAI was negatively correlated with all-cause mortality (HR (95% CI): 0.95(0.91, 0.99), p = 0.01). The RCS analysis showed a nonlinear correlation between DII or CDAI and all-cause mortality. The maximum pro-inflammatory inflection point of DII was 2.32, while the antioxidant threshold of CDAI is −0.12. Subgroup analyses indicated that the relationship between exposure variables and all-cause mortality was stable in most populations.

Conclusion

Reducing the pro-inflammatory diet or increasing the antioxidant diet can reduce all-cause mortality in COPD patients.
Alectinib combined with VRCD and BV monoclonal antibody for the treatment of ALK-positive large B-cell lymphoma: a case report and literature review
Authors: Wang Hongxia , Bai Junjun , Zhang Bei , Pei Zhixin , Zhao Yingxin , Gu Jingjing , Fang Zhiyu , Liu Miaomiao , Liang Xun , Song Qinglin
Published: January 2025

We report a case of a 53-year-old male patient who was diagnosed with anaplastic lymphoma kinase-positive large B-cell lymphoma. A pathological examination showed plasma-cell immunophenotype negative for mature B-lymphocyte markers. The patient received three cycles of an “alectinib + Vincristine + Rituximab + Cyclophosphamide + Doxorubicin (VRCD) “ regimen. In the fourth cycle, brentuximab vedotin monoclonal antibody treatment was added to increase the efficacy of the treatment. Positron emission tomography-computed tomography and a bone marrow examination were carried out after four cycles, revealing a complete response. Stem cells were successfully harvested. Thus far, the patient has undergone six treatment cycles and successfully received autologous hematopoietic stem cell transplantation. Currently, the patient is receiving maintenance therapy with alectinib and lenalidomide and remains in a favorable clinical condition.
MiR-216a-3p inhibits the cytotoxicity of primary natural killer cells
Authors: Abdelbary Rowan , Ragheb Manon , El Sobky Shereen A. , El-Badri Nagwa , Aboud Nourhan , Tawheed Ahmed , Gomaa Asmaa , Zidan Mona , Aziz Ramy K. , Abouzid Abd Elrahman , Salah Radwa Ayman , El-Kassas Mohamed , Waked Imam , Moustafa Ahmed , Fawzy Injie Omar , El-Ekiaby Nada , Abdelaziz Ahmed Ihab
Published: January 2025

Introduction

The role of miRNAs in regulating variable molecular functions has been sought by scientists for its promising utility in regulating the immune response and, hence, in treating various diseases. In hepatocellular carcinoma (HCC) specifically, a reduction in the number and efficiency of circulating and intrahepatic natural killer (NK) cells has been reported. Our project aims to investigate the role of miR-216a-3p in the regulation of NK cell cytotoxicity, especially since it plays a tumor suppressor role in the context of HCC.

Methods

To achieve our aim, we isolated NK cells from the whole blood of 86 patients with HCC and 23 healthy controls. We assessed the expression profile of miR-216a-3p in NK cells of patients and controls. Furthermore, we induced the expression of miR-216a-3p in NK cells isolated from healthy controls, followed by measuring the release of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), perforins (PRF) and granzyme B (GrB) using ELISA as well as NK cells cytolytic activity against Huh7 cells using lactate dehydrogenase (LDH) cytotoxicity assay. After that, we performed an in silico analysis to understand the mechanistic regulation imposed by miR-216a-3p on NK cells to study its impact on one of its potential downstream targets.

Results

Our results have indicated that miR-216a-3p has higher expression in NK cells of patients with HCC, and simulating this elevated expression pattern via forcing miR-216a-3p expression in normal NK cells has negatively impacted the release of TNF- α, IFN- γ, GrB, and PRF. Consequently, a decrease in cell cytolysis was observed. Our in silico analysis revealed that the predicted downstream targets of miR-216a-3p are enriched in the FOXO-signaling pathway. Among those targets is FOXO-1, which has been reported to play a role in NK cell maturation. Thus, we evaluated FOXO-1 expression upon mimicking miR-216a-3p in control NK cells that showed significant downregulation of FOXO-1 on both RNA and protein levels.

Conclusion

In conclusion, we report miR-216-3p as a negative regulator of NK cell cytotoxicity.
Management of CAR-T cell therapy in patients with multiple myeloma: a systematic review and expert consensus in Australia
Authors: Ho P. Joy , Quach Hang , Sidiqi M. Hasib , Lee Cindy H. , Butler Jason , Spencer Andrew , Micklethwaite Kenneth , Li Jingya , Cusson Elissa , Bagnall Robert , Harrison Simon J.
Published: January 2025

Background

Regulatory bodies have recently approved chimeric antigen receptor (CAR)-T cell therapies for patients with multiple myeloma (MM), but the treatment process involves complex decision making. To support the introduction of these therapies, we aimed to establish consensus expert opinion on best practices of all aspects of the management of patients with MM undergoing CAR-T cell therapy in Australia.

Methods

We conducted a modified RAND/UCLA two-round Delphi panel informed by a systematic literature review (SLR). The SLR included evidence from clinical practice guidelines, interventional trials, and observational studies for CAR-T cell therapy for patients with MM, to synthesize methodological aspects of CAR-T cell therapy related to patient management. The Delphi panel comprised eight hematologists from across Australia, each with significant experience directly treating patients using CAR-T therapy or referring patients for CAR-T cell therapy. Panelists completed the surveys electronically, and attended a virtual meeting held before the second-round questionnaire to discuss the first-round questionnaire responses. Consensus was defined a priori as at least 70% agreement on survey questions.

Results

The SLR identified 22 interventional or observational studies and 5 clinical practice guidelines reporting on selection and management of patients with MM treated with CAR-T cell therapy from various global regions. The Delphi panel reached consensus on practices related to patient referral, screening, selection, prioritization, treatments requiring wash-out, bridging therapy, lymphodepletion, infusion, and post-infusion monitoring and management. Most consensus results aligned with consistently recommended practices within guidelines included in the SLR. Consensus was not reached for statements related to specific screening practices and post-treatment monitoring, suggesting differing opinions on the specific best practices to implement.

Conclusion

Our Delphi panel established expert consensus on key considerations for patient selection, administrative processes, and aftercare for patients with MM in Australia undergoing CAR-T therapy. This will guide the development of clinical practice guidelines which are relevant and feasible to Australian health systems.