bluuebunny/crossref_metadata_2025 huggingface dataset:
Penyuluhan Agama Kristen sebagai Psikoedukasi kepada Anak dalam Mencegah Perilaku Bullying di SMPTK Tarus
Authors: Djira Imelda Marina , Ufi Delsylia Tresnawaty , Aseleo Kurniawati , Rita  , Messakh Merling Tonia Litron Litos Conthes , Nulik Eritka A , Haekase Amedniada , Boro Arki , Raynaldo Roberto , Manu Maya Katarina , Kause Apritia Grase
Published: December 2023

Bullying merupakan perilaku yang bertentangan dengan norma agama. Meskipun bertentangan dan dilarang, masih saja terjadi bullying pada anak, baik itu di sekolah dan lingkungan masyarakat. Perilaku ini muncul dan terjadi sampai pada bully fisik yang mengakibatkan kematian. Berbagai masalah traumatik bisa memunculkan masalah-masalah lain yang mengakibatkan suburnya lingkaran perilaku bullying dalam diri pribadi anak dan lingkungan sekitarnya. Maraknya masalah ini tentu saja perlu menjadi perhatian dalam mencegah kekerasan yang terjadi pada anak. Penyuluhan agama kristen sebagai psikoedukasi di SMPTK Tarus penting dilaksanakan dengan tujuan mencegah perilaku bullying. Pada kegiatan ini tim memberikan materi tentang cegah bullying dengan prinsip Alkitab dan psikoedukasi, pembuatan kartu komitmen dan poster stop bullying. Hasil dari kegiatan ini direspon baik dengan antusias dari siswa. Adapun respon dari peserta didapat dari survey kegiatan pada tingkat pemahaman didapat sangat Baik mencapai 80%, pada survey kegiatan penyuluhan agama didapat 96%, sedangkan pada survey pemateri didapat 86%.
Pengenalan Bahasa Mandarin Dasar dan Workshop Etnografi Budaya Tionghoa Sebagai Bekal Softskill Bagi Guru dan Siswa SMPN 03 Tegowanu
Authors: Siregar Sheyra Silvia , Insani Nur Hanifah , Marsuki Ria Riski
Published: December 2023

Perkembangan ekonomi Negara Cina yang pesat saat ini memunculkan fenomena kebutuhan tenaga ahli bahasa Mandarin dengan kualifikasi yang capable di bidangnya. Bersamaan dengan hal tersebut, bahasa mandarin menjadi bahasa asing kedua yang banyak dipelajari baik secara mandiri maupun lembaga. Pengembangan Bahasa Mandarin di Indonesia sebagai bahasa asing terkendala oleh minimnya tenaga pengajar khususnya di Kab. Grobogan sebagai wilayah Industri di Provinsi Jawa Tengah. Kegiatan pengabdian ini bertujuan memperkenalkan Bahasa Mandarin dan etnografi budaya Tionghoa bagi Guru dan Siswa di SMPN 03 Tegowanu sebagai harmonisasi budaya asing dan budaya lokal serta jawaban terhadap tantangan pemenuhan tenaga ahli Bahasa Mandarin di wilayah urban pada era Globalisasi. Kegiatan seminar dan workshop Pengenalan Bahasa Mandarin Dasar dan Etnografi Budaya Tionghoa Di Era Globalisasi Pada Guru dan Siswa di SMPN03 Tegowanu, Jawa Tengah. diselenggarakan di SMPN 03 Tegowanu, Kab. Grobogan. Melalui pelaksanaan kegiatan ini didapati 90% pengetahuan Bahasa Mandarin dan budaya Tionghoa para peserta meningkat.
Pendampingan Manajemen Strategis Pada Perangkat Desa dan Pengelola BUMDes Desa Tanjung Dayang
Authors: Widodo Slamet , Saptawan Ardiyan , Purnama Dadang Hikmah , Alamsyah  , Ismail Rizky Ghoffar , Nurhasan  , Priyanto Langgeng
Published: December 2023

Kegiatan ini bertujuan menguatkan kelembagaan BUMDes “Maju Bersama” di Desa Tanjung Dayang Selatan melalui konsep manajemen strategis dan regulasi teknis tentang BUMDes, tools SWOT dan pohon masalah kepada kepala desa, perangkat desa, dan pengelola BUMDes. Pelaksanaan kegiatan di Kantor Kepala Desa dan diikuti 20 peserta yang merepresentasikan aparatur pemerintahan desa dan pengelola BUMDes. Pertemuan pertama berbentuk ceramah tutorial, sedangkan pertemuan kedua dan ketiga masing-masing berupa praktikum analisis SWOT. Selain berhasil meningkatkan pengetahuan para peserta (sebagaimana ditunjukkan hasil pre-test dan post-test), kegiatan pengabdian ini berhasil menyusun pohon masalah dan matrik strategi yang bisa digunakan para pengelola BUMDes untuk menyusun rencana pengembangan bisnis mereka. Tim pengabdian merekomendasikan kepada kepala desa Tanjung Dayang Selatan untuk mengalokasikan dana desa guna pembukaan unit-unit usaha baru yang berhasil diidentifikasi kegiatan ini. Tim Universitas Sriwijaya, tim pengabdian merekomendasikan agar penguatan kelembagaan BUMDes “Maju Bersama” di Desa Tanjung Dayang Selatan dapat dilanjutkan di masa mendatang.
Workshop Pembuatan E-Book Pembelajaran IPS Menggunakan Aplikasi Flipbook Bagi Guru Fogipsi Wilayah Kalimantan Barat
Authors: Barella Yusawinur , Wiyono Hadi , Buwono Sri , Aminuyati  , Karolina Venny , Fafizi Muhammad
Published: December 2023

Pengabdian Kepada Masyarakat ini dilaksanakan terhadap25 orang guru IPS yang tergabung dalam FOGIPSI wilayah Kalimantan Barat, dalam bentuk pelatihan dan pendampingan Pembuatan Ebook  pembelajaran IPS Menggunakan Aplikasi Flipbook.  Adapun tujuan dari pelaksanaan Pengabdian ini adalah agar guru dapat mengetahui fungsi fitur dalam aplikasi flipbook, mengetahui urutan tahapan  pembuatan ebook IPS dengan aplikasi flipbook, dan dapat mengetahui cara mengaitkan audio, gambar dan video dalam ebook IPS  dengan aplikasi flipbook. Metode yang diterapkan dalam pelaksanaan pengabdian ini mencakup persiapan, sosialiasi terhadap partisipan, pelatihan dan demonstrasi, praktek, dan presentasi. Adapun hasil dari Pelaksanaan pengabdian ini adalah 1). Peserta yang merupakan guru IPS mampu mengenali fungsi fitur dari aplikasi Flipbook; 2) para guru mampu memahami urutan tahapan dari pembuatan e-book IPS dengan aplikasi Flipbook; dan para guru tersebut mampu untuk mengaitkan suara dan gambar pada e-book yang telah dibuat.
Sosialisasi Pengenalan Pendidikan dalam Meningkatkan Kesadaran Masyarakat Desa Tambak Ukir Terhadap Pentingnya Pendidikan di Masa Depan
Authors: Seituni Siti , Ambarsari Ida Fitriana , Hasanah Nur , Afia Nur
Published: December 2023

Berdasarkan hasil observasi dilaksanakan di Desa Tambak Ukir diketahui bahwa masih banyak Masyarakat yang mengesampingkan pendidikan dan masih banyaknya pernikahan dini sehingga diperlukan adanya kegiatan pengabdian kepada masyarakat yang berupa sosialisasi tentang pemahaman dan pemberian motivasi-motivasi terkait pentingnya pendidikan. Motivasi-motivasi ini diberikan dengan pemutaran video terkait pentingnya pendidikan dan berpendidikan di masa depan memiliki tujuan untuk meningkatkan kesadaran masyarakat khususnya di desa Tambak Ukir, kecamatan kendit. Kegiatan ini dilaksanakan di SDN 1 Tambak Ukir dengan jumlah peserta sebanyak 44 orang. Metode yang digunakan pada kegiatan pengabdian kepada masyarakat ini adalah perkenalan tentang maksud dan tujuan kegiatan, dilanjutkan dengan metode ekspositori yaitu penyampaian materi dan ditutup dengan evaluasi materi yaitu berupa pemberian quiz dan hadiah untuk peserta. Lebih lanjut, hasil dari kegiatan pengabdian kepada masyarakat ini dapat dilihat dari beberapa kriteria, yaitu ketercapaian target jumlah peserta pengabdian, ketercapaian tujuan pengabdian, dan kemampuan peserta dalam memahami materi dan kebermanfaatan kegiatan PkM. Berdasarkan hasil dari beberapa kriteria tersebut diketahui bahwa seluruh kriteria tercapai dengan hasil yang sangat baik.
Terkikisnya kemampuan mitigasi bencana masyarakat kepulauan
Authors: Susanti Evi , Mahmudah Ika Zulkafika , Saputra Hijrah
Published: December 2023

Dibalik keindahan alam Indonesia tersimpan suatu risiko bagi Masyarakat kepulauan akan bahaya bencana. Masyarakat keupualauan sering disebut sebagai masyarakat yang jauh, tertinggal dan terbelakang dari peradaban, akibat letaknya yang jauh dari peradaban kota, tidak hanya tertinggal informasi, bahkan pemutakiran data terkait wilayah rentan bencana seringkali tidak optimal. Program edukasi berbasis pendekatan masyarkat dikepulauan dilakukan yang bertujuan untuk meningkatkan kapasitas masyrakata dalam menghadapi potensi bencana di kepulauan. Berdasarkan hasil pre-test dan post-test rata-rata pengetahuan tentang kerentanan meningkat sebanyak 9% dari 84,7% menjadi 94,10%, pada pengetahuan tentang ancaman meningkat sebanyak 28,2% dari 45,90% menjadi 74,10%, sedangkan pada pengetahuan tentang mitigasi meningkat sebanyak 23,6% dari 62,90% menjadi 86,50%. Hasil dari identifikasi yang telah dilakukan adalah kerentanan yang dapat dilihat dari beberapa faktor, yakni faktor fisik, faktor sosial, faktor ekonomi dan faktor lingkungan. Sedangkan potensi ancaman bencana yang teridentifikasi adalah bencana kebakaran pemukiman, banjir, gelombang pasang, gempa bumi dan tsunami. Kemampuan mitigasi masyarakat kepulauan masih kurang dan perlu dilakukan peningkatan.
TERAPI NEUROPROTEKTIF ENDOGEN MENGGUNAKAN EBSELEN UNTUK MEMPERKUAT EFEK KONJUGASI SMALL UBIQUITIN-LIKE MODIFIER (SUMO) PADA STROKE ISKEMIK
Authors: Ivan Ignatius , Stella Maureen Miracle , Tandarto Kevin , Santosa Mariani
Published: December 2023

Penyakit serebro-kardiovaskular semakin banyak dialami oleh masyarakat dunia hingga saat ini. Di Indonesia sendiri menurut data Riskesdas tahun 2018, kasus stroke tertinggi yang didiagnosa tenaga kesehatan adalah usia 75 tahun keatas (50,2%) dan terendah pada kelompok usia 15-24 tahun (0,6%). Salah satu jenis stroke yakni stroke iskemik terjadi karena adanya tromboembolisme yang menyumbat arteri di serebrum yang selanjutnya dapat menyebabkan iskemia otak fokal¸ kematian sel otak, kerusakan saraf sensoris, motoris, dan gangguan kognitif. Akhir-akhir ini ditemukan suatu inovasi terbaru dalam mencegah kematian sel neuron di otak dengan memanfaatkan protein small ubiquitin-like modifier (SUMO) sebagai sumber neuroprotektif endogen ketika terjadi stroke iskemik. Ide ini berasal dari penemuan pada tupai tanah bergaris 13 (Ictidomys tridecemlineatus) yang ketika melakukan hibernasi terutama pada fase torpor, walaupun aliran darah ke otaknya berkurang, konsumsi energinya menurun, dan suhu tubuh berada dalam keadaan letal (sekitar 5oC), namun tetap dapat mempertahankan proses homeostasis dalam tubuh serta tanpa adanya kerusakan pada sel otak. SUMO ditemukan pada seluruh mamalia dan oleh karena itu protein ini dapat dijadikan sebagai target terapi untuk penyakit stroke iskemik pada manusia.
Peran Neuregulin-1 (NRG-1), Acidic Fibroblast Growth Factor (FGF), dan Vascular Endothelial Growth Factor (VEGF) pada Sel Perisit sebagai Inovasi Terbaru Penanganan Infark Miokard akibat Aterosklerosis
Authors: Ivan Ignatius , Widjanarko Nicolas Daniel , Sudharta Harvey , Stella Maureen Miracle , Tandarto Kevin , Santosa Mariani
Published: December 2023

Infark miokard telah mengakibatkan 17 juta kematian di seluruh dunia pada tahun 2005. Hal ini terutama disebabkan karena terjadinya nekrosis sel miokard akibat iskemia jangka panjang. Agen trombolitik tidak memiliki pengaruh dalam meregenerasi pembuluh darah yang pecah. Oleh karena itu, banyak sel induk pembuluh darah, terutama perisit, dibawa untuk merangsang pembangunan, pematangan, rekonstruksi, dan mempertahankan permeabilitas pembuluh baru. Di sisi lain, beberapa faktor pertumbuhan seperti Neuregulin-1 (NRG-1), Acidic Fibroblas Growth Factor  (FGF), dan Vascular Endothelial Growth Factor (VEGF) juga memainkan peran dalam angiogenesis yang merupakan jalur utama proses penyembuhan akibat iskemia. Tujuan dari kajian ilmiah ini adalah untuk menjelaskan peran perisit yang distimulasi oleh leptin, bersama dengan beberapa faktor pertumbuhan yang diselubungi oleh mikropartikel sebagai terapi baru infark miokard yang terutama disebabkan oleh aterosklerosis. Hasil kajian menunjukkan bahwa perisit memiliki kemampuan untuk berdiferensiasi menjadi sel otot polos, sel saraf, dan sel endotel. Proses ini dipengaruhi oleh leptin dan juga beberapa faktor pertumbuhan yang diselubungi oleh mikropartikel untuk meningkatkan stabilitas dan imunitas terhadap makrofag. Terapi sel punca dengan menggunakan perisit yang distimulasi oleh leptin dan faktor pertumbuhan yang diselubungi oleh mikropartikel dapat menjadi metode pengobatan infark miokard yang menjanjikan di masa depan.
Skrining Berbasis Ponsel Pintar: Alat Deteksi Midkine, Adiponectin¸ Apolipoprotein C-1, Kidney Injury Molecule-1 sebagai Biomarker Obstruksi Arteri Koroner
Authors: Ivan Ignatius , Stella Maureen Miracle , Tandarto Kevin , Santosa Mariani
Published: December 2023

Penyakit Jantung Koroner (PJK) adalah penyakit akibat penumpukan plak di dalam arteri koroner yang menyuplai oksigen ke jantung. Diketahui bahwa penyakit kardiovaskuler menyebabkan kematian sebanyak >17 juta orang setiap tahunnya dimana 42,3% diakibatkan oleh PJK. Melalui perkembangan teknologi kedokteran dan mengingat masyarakat dunia yang banyak memiliki ponsel pintar (6.4 triliun pengguna pada tahun 2021, maka kedua bidang ini mulai dikombinasikan. Cara deteksi biomarker ((midkine, adiponectin, apolipoprotein C-1 [ApoC-1], dan kidney injury molecule-1 [KIM-1]) melalui imunofluorosensi dengan alat portabel berbasis ponsel pintar dapat menjadi terobosan untuk mendeteksi Obstruksi Arteri Koroner yang Signifikan (OAKS). Dengan menggunakan konsep alat diagnosis portabel dan memiliki kemampuan multiplexing diharapkan 4 biomarker OAKS dapat terdeteksi dengan lebih mudah, cepat, tepat dan tanpa membutuhkan keahlian khusus sehingga pada akhirnya alat ini mampu menjangkau seluruh tingkat layanan kesehatan masyarakat terutama yang bersifat layanan primer.
Diagnosis of Mechanoluminescent Crack Based on Double Deep Learning in Al 7075
Authors: Park Tae O , Shin Youn Woo , Lee Seung Hwan , Jwa Pius , Kwon Yong Nam , Timilsina Suman , Jang Seong Min , Jo Chul Woo , Kim Ji Sik
Published: December 2023

The phenomenon of mechanoluminescence (ML) refers to the emission of light induced by mechanical stimulation applied to mechano-optical materials for example SrAl2O3:Eu,Dy (SAO). Numerous technologies on the basis of ML have been presented to visualize the stress or strain in various structures for the applications including structural health monitoring. As a result, extensive attention has been devoted to the design, synthesis, characteristics, optimizations, and applications of ML materials. However, challenges still remain in the standardization of ML measurement and evaluation, thereby commercially viable ML applications are currently unavailable. To overcome these difficulties, present study proposes ML measurement and evaluation techniques employing the ML fracture mechanics, finite element method, and dual deep learnings. For the effective normalization of visualized ML images under fixed initial ML intensity condition, continuous UV irradiation above the critical ML power density has been subjected to tensile and compact tension (CT) specimens. Therefore, Plastic Stress Intensity Factor (SIF) as well as crack tip stress field have been extracted successfully from normalized ML images based on ML fracture mechanics. To complement and verify the ML analysis, numerical FEM simulation and analytical ASTM calculation have been also provided. Finally, a double deep learning consists of Generative Adversarial Networks (GAN) and Convolutional Neural Networks (CNN) has been trained and tested for the standard evaluation of in-situ ML images.
On Some Possible Differences between Punctuation Marks in the Chinese and Spanish Languages
Authors: Galloso Camacho María Victoria , Zhang Bo
Published: December 2023

Languages vary in spelling and grammar. Starting from Didactics in the field of Language and Applied Linguistics, our research is conducted on suprasegmental features: contrastive analysis for future Spanish teachers to native Mandarin speakers. Punctuation marks are essential for correctly understanding any written text in any language. However, they are not the same for each language, nor do they have the same usage or form. This work formulates a research proposal to compare the following punctuation marks in Chinese and Spanish: period or full stop, comma, question marks, and hyphen, which are the most commonly used and, above all, because the differences between them are more representative. To achieve this objective, it starts from the deficiencies in the use of these marks in both languages and reflection on the historical ignorance regarding their usage, form, and possible similarities between Chinese and Spanish segments. We conclude with the idea that the formal dissimilarity between certain Spanish and Chinese punctuation marks, such as the full stop and the question mark, does not cause extraordinary difficulties for Chinese speakers in acquiring their correct use in Spanish. Those signs whose forms share similarities, such as the comma and quotation marks, do represent acquisition difficulties. In order to specify the scope of this phenomenon on punctuation, in the future it will logically be necessary to study more punctuation signs, such as semicolons, colons, as well as ellipses.
A co-designed, community-based intensive health behavior intervention promotes participation and engagement in youth with risk factors for type 2 diabetes
Authors: Pike Julie M. , Haberlin-Pittz Kathryn M. , Alharbi Basmah S. , Perkins Susan M. , Hannon Tamara S.
Published: December 2023

Background

Obesity among youth (children and adolescents) is associated with increased risk for youth-onset type 2 diabetes. Lifestyle change can delay or prevent the development of type 2 diabetes, yet real-world implementation of health behavior recommendations is challenging. We previously engaged youth with risk factors for type 2 diabetes, their caregivers, and professionals in a human-centered design study to co-design a lifestyle change program. Here we report the outcomes for this 16-week co-designed lifestyle change program for youth at risk for T2D and their caregivers.

Research design and methods

This single-arm family-based cohort study included youth aged 7-18 years, with BMI ≥85th percentile (overweight or obese) and at least one additional risk factor for type 2 diabetes, and their caregivers. Clinical (BMI, HbA1c), self-reported physical activity, and quality of life outcomes were evaluated at baseline (B), post-intervention (M4), and 1 year (M12) following the intervention.

Results

Seventy-eight youth (mean age 12.4 ± 2.7y, 67% female, 37.8% white) and 65 caregivers were included in the data analysis. Youth baseline BMI z-scores (2.26 ± 0.47) and HbA1c (5.3 ± 0.3) were unchanged at follow up time points [BMI z-scores M4 (2.25 ± 0.52), M12 (2.16 ± 0.58), p-value 0.46], [HbA1c M4 (5.3 ± 0.3), M12 (5.2 ± 0.3), p-value (0.04)]. Youth reported increased physical activity at M4 (p = 0.004), but not at M12. Youth quality of life scores increased at M12 (p=0.01). Families who attended at least one session (n=41) attended an average of 9 out of 16 sessions, and 37 percent of families attended 13 or more sessions.

Conclusion

A co-designed, community-based lifestyle intervention promotes increased physical activity, improved quality of life, maintenance of BMI z-scores and HbA1c, and engagement in youth with risk factors for T2D.
Performance of next-generation sequencing for diagnosis of blood infections by Klebsiella pneumoniae
Authors: Wang Lei , Liu Na , Zhang Lin , Cui Likun , Zhu Mengdie , Li Zhifang , Wang Panpan , Wang Zhengbin
Published: December 2023

Objective

Klebsiella pneumoniae (Kp) bloodstream infections (BSI) can be a life-threatening opportunistic infection. We aimed to evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) for Kp BSI.

Methods

We retrospectively analyzed 72 patients suspected with bloodstream infection and mNGS Kp positive in peripheral blood, who were hospitalized in our hospital from January 2022 to January 2023. Clinical data and laboratory parameters were collected. All patients had blood drawn and other samples for blood mNGS, blood cultures (BC) and other cultures (OC). The accuracy of mNGS results was analyzed according to infection site, clinical indicators, therapeutic effect and routine culture results. The detection of pathogenic microorganisms by blood mNGS and routine culture was compared.

Results

Among 72 infection patients, 29 cases (40.28%) were BC positive, 43 cases (59.72%) were other culture (OC) positive, 16 cases (22.22%) were both BC and OC positive, 56 cases were positive for both mNGS and routine culture. Among the 56 double-positive cases, mNGS and conventional cultures were completely consistent in 27 cases, partially consistent in 15 cases, and completely inconsistent in 14 cases. Using the clinical diagnosis as the reference standard, There were 51 cases consistent with the results of mNGS with Kp BSI, the clinical consistency was 70.83% (51/72). The coincidence rate of mNGS and clinical diagnosis was higher than that of BC (54.17%, 39/72), indicating a statistically significant difference between the two methods (P<0.01).

Conclusions

Current evidence indicates that mNGS exhibits excellent accuracy for the diagnosis of Kp BSI. Although it cannot replace blood culture detection technology, it can be used as a supplement to provide stronger diagnostic capabilities for BSI and optimize treatment.
Carbapenemase genes distribution in clonal lineages of Acinetobacter baumannii: a comprehensive study on plasmids and chromosomes
Authors: Beig Masoumeh , Badmasti Farzad , Solgi Hamid , Nikbin Vajihe Sadat , Sholeh Mohammad
Published: December 2023

Background

The global spread of plasmids carrying carbapenemase genes within carbapenem resistant Acinetobacter baumannii (CRAB) strains poses a worldwide public health issue. In this study, we conducted a comprehensive genetic analysis of plasmids and chromosomes harboring the major carbapenemase genes (blaNDM, blaKPC, blaVIM, blaIMP, blaGES, blaOXA-58-like, blaOXA-24/40-like, blaOXA-143-like, and blaOXA-23-like) in CRAB strains using bioinformatic tools.

Methods

We retrieved plasmids and chromosomes carrying the major carbapenemase genes from GenBank. The size, replicon type, and conjugal apparatus of the plasmids were also determined. Furthermore, allele types, co-existence of other antimicrobial resistance genes alongside carbapenemases in plasmids or chromosomes, co-occurrence of carbapenemase genes, gene repetition, and sequence types (ST) of whole genomes were characterized.

Results

The database contained 113 plasmids and 38 chromosomes harboring carbapenemase genes. This investigation revealed that blaNDM and blaOXA-58-like were the predominant allele types in both the plasmids and chromosomes. Nine (7.96%) plasmids with blaNDM-1 were potentially conjugative. The most common replicon types of the plasmids were R3-T1, R3-T8, R3-T2, R3-T23, and RP-T1. The analysis revealed that blaNDM-1 and blaOXA-58-like genes possessed the highest variety of co-existence with other antibiotic resistance genes. The co-occurrence of dual carbapenemases was identified in 12 plasmids and 19 chromosomes. Carbapenemase gene repetitions were identified in 10 plasmids and one chromosome. Circular alignment revealed that the plasmids carrying the co-occurrence of blaNDM-1 and blaOXA-58 were more homogeneous. However, there was heterogeneity in certain regions of these plasmids. According to the minimum spanning tree (MST) results, the majority of the plasmids belonged to the genomes of ST2Pas, ST1Pas, ST422Pas, ST622Pas, and ST85Pas.

Conclusion

A. baumannii appears to have a strong ability for genome plasticity to incorporate carbapenemase genes on its plasmids and chromosomes to develop resistance against carbapenems. Mobilizable plasmids harboring carbapenemases significantly contribute to the dissemination of these genes. The genetic structure of the plasmids revealed a strong associations of class I integrons, ISAba-like structures, Tn4401 elements, and aac (6′)-Ib with carbapenemases. Furthermore, gene repetition may also be associated with carbapenem heteroresistance.
Development of an interpretable machine learning-based intelligent system of exercise prescription for cardio-oncology preventive care: A study protocol
Authors: Gao Tianyu , Ren Hao , He Shan , Liang Deyi , Xu Yuming , Chen Kecheng , Wang Yufan , Zhu Yuxin , Dong Heling , Xu Zhongzhi , Chen Weiming , Cheng Weibin , Jing Fengshi , Tao Xiaoyu
Published: December 2023

Background

Cardiovascular disease (CVD) and cancer are the first and second causes of death in over 130 countries across the world. They are also among the top three causes in almost 180 countries worldwide. Cardiovascular complications are often noticed in cancer patients, with nearly 20% exhibiting cardiovascular comorbidities. Physical exercise may be helpful for cancer survivors and people living with cancer (PLWC), as it prevents relapses, CVD, and cardiotoxicity. Therefore, it is beneficial to recommend exercise as part of cardio-oncology preventive care.

Objective

With the progress of deep learning algorithms and the improvement of big data processing techniques, artificial intelligence (AI) has gradually become popular in the fields of medicine and healthcare. In the context of the shortage of medical resources in China, it is of great significance to adopt AI and machine learning methods for prescription recommendations. This study aims to develop an interpretable machine learning-based intelligent system of exercise prescription for cardio-oncology preventive care, and this paper presents the study protocol.

Methods

This will be a retrospective machine learning modeling cohort study with interventional methods (i.e., exercise prescription). We will recruit PLWC participants at baseline (from 1 January 2025 to 31 December 2026) and follow up over several years (from 1 January 2027 to 31 December 2028). Specifically, participants will be eligible if they are (1) PLWC in Stage I or cancer survivors from Stage I; (2) aged between 18 and 55 years; (3) interested in physical exercise for rehabilitation; (4) willing to wear smart sensors/watches; (5) assessed by doctors as suitable for exercise interventions. At baseline, clinical exercise physiologist certificated by the joint training program (from 1 January 2023 to 31 December 2024) of American College of Sports Medicine and Chinese Association of Sports Medicine will recommend exercise prescription to each participant. During the follow-up, effective exercise prescription will be determined by assessing the CVD status of the participants.

Expected outcomes

This study aims to develop not only an interpretable machine learning model to recommend exercise prescription but also an intelligent system of exercise prescription for precision cardio-oncology preventive care.

Ethics

This study is approved by Human Experimental Ethics Inspection of Guangzhou Sport University.

Clinical trial registration

http://www.chictr.org.cn, identifier ChiCTR2300077887.
Sleep disturbance exacerbates atherosclerosis in type 2 diabetes mellitus
Authors: Fan Bingge , Tang Ting , Zheng Xiao , Ding Haixia , Guo Peng , Ma Hongqing , Chen Yu , Yang Yichao , Zhang Lihui
Published: December 2023

Background

Short sleep duration and poor sleep quality are important risk factors for atherosclerosis. The use of smart bracelets that measure sleep parameters, such as sleep stage, can help determine the effect of sleep quality on lower-extremity atherosclerosis in patients with type 2 diabetes.

Objective

To investigate the correlation between sleep disorders and lower-extremity atherosclerosis in patients with type 2 diabetes.

Methods

After admission, all patients were treated with lower-extremity arterial ultrasound and graded as having diabetic lower-extremity vascular lesions according to the results. A smart bracelet was used to obtain the patient sleep data. The correlation between sleep patterns and diabetic lower-extremity atherosclerosis, diabetic foot, and various metabolic indices was verified.

Results

Between August 2021 and April 2022, we screened 100 patients with type 2 diabetes, with 80 completing sleep monitoring. Univariate ordered logistic regression analysis indicated that patients with a sleep score below 76 (OR = 2.707, 95%CI: 1.127–6.488), shallow sleep duration of 5.3 h or more (OR=3.040, 95 CI: 1.005–9.202), wakefulness at night of 2.6 times or more (OR = 4.112, 95%CI: 1.513–11.174), and a deep sleep continuity score below 70 (OR = 4.141, 95%CI: 2.460–615.674) had greater risk of high-grade lower limb atherosclerosis. Multivariate ordinal logistic regression analysis revealed that the risk of high-grade lower limb atherosclerosis was higher in patients with 2.6 or more instances of nighttime wakefulness (OR = 3.975, 95%CI: 1.297–12.182) compared with those with fewer occurrences. The sleep duration curve of patients with different grades of diabetic lower-extremity atherosclerosis was U-shaped. According to the results of the one-way analysis of variance, the higher the deep sleep continuity score, the lower the Wagner scale score for diabetic foot (P < 0.05).

Conclusions

Sleep disorders (long, shallow sleep duration, frequent wakefulness at night, and poor continuity of deep sleep) can worsen lower limb atherosclerosis in patients with type 2 diabetes. This finding can provide a new method for medical professionals to prevent and treat diabetic lower-extremity vascular lesions.
Rationale and design of the Children's Oncology Group study AAML1831 integrated cardiac substudies in pediatric acute myeloid leukemia therapy
Authors: Leger Kasey J. , Robison Nora , Narayan Hari K. , Smith Amanda M. , Tsega Tenaadam , Chung Jade , Daniels Amber , Chen Zhen , Englefield Virginia , Demissei Biniyam G. , Lefebvre Benedicte , Morrow Gemma , Dizon Ilona , Gerbing Robert B. , Pabari Reena , Getz Kelly D. , Aplenc Richard , Pollard Jessica A. , Chow Eric J. , Tang W. H. Wilson , Border William L. , Sachdeva Ritu , Alonzo Todd A. , Kolb E. Anders , Cooper Todd M. , Ky Bonnie
Published: December 2023

Background

Pediatric acute myeloid leukemia (AML) therapy is associated with substantial short- and long-term treatment-related cardiotoxicity mainly due to high-dose anthracycline exposure. Early left ventricular systolic dysfunction (LVSD) compromises anthracycline delivery and is associated with inferior event-free and overall survival in de novo pediatric AML. Thus, effective cardioprotective strategies and cardiotoxicity risk predictors are critical to optimize cancer therapy delivery and enable early interventions to prevent progressive LVSD. While dexrazoxane-based cardioprotection reduces short-term cardiotoxicity without compromising cancer survival, liposomal anthracycline formulations have the potential to mitigate cardiotoxicity while improving antitumor efficacy. This overview summarizes the rationale and methodology of cardiac substudies within AAML1831, a randomized Children's Oncology Group Phase 3 study of CPX-351, a liposomal formulation of daunorubicin and cytarabine, in comparison with standard daunorubicin/cytarabine with dexrazoxane in the treatment of de novo pediatric AML.

Methods/design

Children (age <22 years) with newly diagnosed AML were enrolled and randomized to CPX-351-containing induction 1 and 2 (Arm A) or standard daunorubicin and dexrazoxane-containing induction (Arm B). Embedded cardiac correlative studies aim to compare the efficacy of this liposomal anthracycline formulation to dexrazoxane for primary prevention of cardiotoxicity by detailed core lab analysis of standardized echocardiograms and serial cardiac biomarkers throughout AML therapy and in follow-up. In addition, AAML1831 will assess the ability of early changes in sensitive echo indices (e.g., global longitudinal strain) and cardiac biomarkers (e.g., troponin and natriuretic peptides) to predict subsequent LVSD. Finally, AAML1831 establishes expert consensus-based strategies in cardiac monitoring and anthracycline dose modification to balance the potentially competing priorities of cardiotoxicity reduction with optimal leukemia therapy.

Discussion

This study will inform diagnostic, prognostic, preventative, and treatment strategies regarding cardiotoxicity during pediatric AML therapy. Together, these measures have the potential to improve leukemia-free and overall survival and long-term cardiovascular health in children with AML.

Clinical trial registration:https://clinicaltrials.gov/, identifier NCT04293562
Latest development of approved COVID-19 drugs and COVID-19 drugs undergoing late stage clinical trials
Authors: Feng Bingru , Fu Kai
Published: December 2023

As the world adapts to living with SARS-CoV-2, the continuous emergence of new variants has become a primary focus of current studies. In this review, we examined a range of available COVID-19 drugs, including FDA-regulated drugs and those undergoing late-stage clinical trials. Some FDA-regulated drugs, such as Veklury (remdesivir), Olumiant (baricitinib), and Actemra (tocilizumab), have garnered primary clinical status in treatment guidelines, supported by sufficient clinical evidence. Conversely, EUA-authorized therapies, such as some antiviral agents, have demonstrated lower efficacy due to the virus’s constant mutation. We also focused on COVID-19 drugs undergoing late-stage clinical trials, some of which have raised controversy in their administration, such as colchicine and corticosteroids, while others are worth exploring regarding their timing. Several ongoing multi-drug clinical trials are of particular interest, including the “MEDIC-LAUMC” trial that explores drug co-administration, and “ACTIV-2” and “ACTIV-3” trials that compare the effects of different drugs for non-hospitalized and hospitalized patients, respectively. These ongoing clinical trials at a late stage provide essential clinical evidence for future drug authorization and have the potential to provide better drug administration strategies for COVID-19 variants. We look forward to the continued exploration of drug co-administration, comprehensive clinical evidence for treatment, and the investigation of different potential drug utilization.
PPARG dysregulation as a potential molecular target in adrenal Cushing's syndrome
Authors: Vetrivel Sharmilee , Tamburello Mariangela , Oßwald Andrea , Zhang Ru , Khan Ali , Jung Sara , Baker Jessica E. , Rainey William E. , Nowak Elisabeth , Altieri Barbara , Detomas Mario , Watts Deepika , Williams Tracy Ann , Wielockx Ben , Beuschlein Felix , Reincke Martin , Sbiera Silviu , Riester Anna
Published: December 2023

Background

We performed a transcriptomic analysis of adrenal signaling pathways in various forms of endogenous Cushing’s syndrome (CS) to define areas of dysregulated and druggable targets.

Methodology

Next-generation sequencing was performed on adrenal samples of patients with primary bilateral macronodular adrenal hyperplasia (PBMAH, n=10) and control adrenal samples (n=8). The validation groups included cortisol-producing adenoma (CPA, n=9) and samples from patients undergoing bilateral adrenalectomy for Cushing’s disease (BADX-CD, n=8). In vivo findings were further characterized using three adrenocortical cell-lines (NCI-H295R, CU-ACC2, MUC1).

Results

Pathway mapping based on significant expression patterns identified PPARG (peroxisome proliferator-activated receptor gamma) pathway as the top hit. Quantitative PCR (QPCR) confirmed that PPARG (l2fc<-1.5) and related genes – FABP4 (l2fc<-5.5), PLIN1 (l2fc<-4.1) and ADIPOQ (l2fc<-3.3) – were significantly downregulated (p<0.005) in PBMAH. Significant downregulation of PPARG was also found in BADX-CD (l2fc<-1.9, p<0.0001) and CPA (l2fc<-1.4, p<0.0001). In vitro studies demonstrated that the PPARG activator rosiglitazone resulted in decreased cell viability in MUC1 and NCI-H295R (p<0.0001). There was also a significant reduction in the production of aldosterone, cortisol, and cortisone in NCI-H295R and in Dihydrotestosterone (DHT) in MUC1 (p<0.05), respectively.

Outcome

This therapeutic effect was independent of the actions of ACTH, postulating a promising application of PPARG activation in endogenous hypercortisolism.
The causal association between smoking, alcohol consumption and risk of upper urinary calculi: insights from a Mendelian randomization study
Authors: Wang Li , Yin Shan , Li Kun-peng , Bao Er-hao , Wang Jia-hao , Zhu Ping-yu
Published: December 2023

Background: The causal link between smoking, alcohol consumption, and upper urinary calculi remains uncertain in observational studies due to confounding factors. To uncover potential causal associations, we utilized two-sample univariable and multivariable Mendelian randomization (MR) methods.

Methods: Five risk factors related to lifestyles (cigarettes per day, lifetime smoking index, smoking initiation, drinks per week and alcohol intake frequency) were chosen from the Genome-Wide Association Study (GWAS). Upper urinary calculi were obtained from the FinnGen and United Kingdom Biobank consortium. Inverse-variance-weighted (IVW) was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl). While diligently scrutinizing potential sources of heterogeneity and horizontal pleiotropy via the rigorous utilization of Cochran’s Q test, the MR-PRESSO method, and MR-Egger.

Results: The summary OR for upper urinary calculi was 0.6 (IVW 95% CI: 0.49–0.74; p = 1.31 × 10−06) per standard deviation decrease in drinks per week. Interestingly, the genetically predicted alcohol intake frequency was associated with a significantly increased risk upper urinary calculi (OR = 1.27; 95% CI: 1.11–1.45; p = 0.0005). Our study found no association between smoking initiation, the number of cigarettes per day, and the lifetime smoking index and the risk of upper urinary calculi. By adjusting for body mass index and education, estimates of drinks per week remained consistent in multivariate MR analyses, while alcohol intake frequency became non-significant.

Conclusion: MR analysis showed that drinks per week was negatively associated with upper urinary calculi, whereas the effect of tobacco on upper urinary calculi was not significant and the detrimental effect of alcohol intake frequency on upper urinary calculi became non-significant after adjusting for BMI and education.
The non-canonical inflammasome activators Caspase-4 and Caspase-5 are differentially regulated during immunosuppression-associated organ damage
Authors: Ghait Mohamed , Duduskar Shivalee N. , Rooney Michael , Häfner Norman , Reng Laura , Göhrig Bianca , Reuken Philipp A. , Bloos Frank , Bauer Michael , Sponholz Christoph , Bruns Tony , Rubio Ignacio
Published: December 2023

The non-canonical inflammasome, which includes caspase-11 in mice and caspase-4 and caspase-5 in humans, is upregulated during inflammatory processes and activated in response to bacterial infections to carry out pyroptosis. Inadequate activity of the inflammasome has been associated with states of immunosuppression and immunopathological organ damage. However, the regulation of the receptors caspase-4 and caspase-5 during severe states of immunosuppression is largely not understood. We report that CASP4 and CASP5 are differentially regulated during acute-on-chronic liver failure and sepsis-associated immunosuppression, suggesting non-redundant functions in the inflammasome response to infection. While CASP5 remained upregulated and cleaved p20-GSDMD could be detected in sera from critically ill patients, CASP4 was downregulated in critically ill patients who exhibited features of immunosuppression and organ failure. Mechanistically, downregulation of CASP4 correlated with decreased gasdermin D levels and impaired interferon signaling, as reflected by decreased activity of the CASP4 transcriptional activators IRF1 and IRF2. Caspase-4 gene and protein expression inversely correlated with markers of organ dysfunction, including MELD and SOFA scores, and with GSDMD activity, illustrating the association of CASP4 levels with disease severity. Our results document the selective downregulation of the non-canonical inflammasome activator caspase-4 in the context of sepsis-associated immunosuppression and organ damage and provide new insights for the development of biomarkers or novel immunomodulatory therapies for the treatment of severe infections.
The dual role of interleukin-6 in Crohn’s disease pathophysiology
Authors: Alhendi Ala’ , Naser Saleh A.
Published: December 2023

Interleukin-6 (IL-6) is a key mediator cytokine of the immune response as well as a regulator of many physiological and pathological processes. In Crohn’s disease (CD), cytokine imbalance rules the intestinal microenvironment and leads to chronic inflammation of the gut. Pro-inflammatory cytokines are generally upregulated in inflammatory bowel disease (IBD) including TNFα and IL-6. Consequently, drugs that target these cytokines have been long sought and approved. Despite the short-term success in treating CD patients with anti-TNFα, many patients stopped responding to treatment, which made IL-6 an alternative target to alleviate inflammation in these patients. IL-6 has long been approached as part of the therapeutic strategies to treat CD and other inflammatory disorders. Clinical trials of CD patients have targeted IL-6 signaling in different mechanisms: blocking IL-6, neutralizing IL-6 receptor (IL-6R), or trapping the soluble IL-6/IL-6R complex. These trials have faced challenges and side effects in patients with gastrointestinal perforations and ulcers, for example, all of which highlight the dual role of IL-6 during intestinal inflammation and the need for this cytokine for intestinal tissue integrity. IL-6 is involved in a complex of upstream regulators and downstream signaling cascades and maintaining a physiological level of IL-6 in the blood and in the intestine is key for achieving health and homeostasis. In this review, we describe IL-6 biology and signaling and its involvement in intestinal health and inflammation. We also discuss the current strategies for targeting IL-6 pathways in CD patients, as well as molecular regulators representing potential therapeutic targets for IL-6 attenuation.
Roles of inflammatory cell infiltrate in periprosthetic osteolysis
Authors: Panez-Toro Isidora , Heymann Dominique , Gouin François , Amiaud Jérôme , Heymann Marie-Françoise , Córdova Luis A.
Published: December 2023

Classically, particle-induced periprosthetic osteolysis at the implant–bone interface has explained the aseptic loosening of joint replacement. This response is preceded by triggering both the innate and acquired immune response with subsequent activation of osteoclasts, the bone-resorbing cells. Although particle-induced periprosthetic osteolysis has been considered a foreign body chronic inflammation mediated by myelomonocytic-derived cells, current reports describe wide heterogeneous inflammatory cells infiltrating the periprosthetic tissues. This review aims to discuss the role of those non-myelomonocytic cells in periprosthetic tissues exposed to wear particles by showing original data. Specifically, we discuss the role of T cells (CD3+, CD4+, and CD8+) and B cells (CD20+) coexisting with CD68+/TRAP− multinucleated giant cells associated with both polyethylene and metallic particles infiltrating retrieved periprosthetic membranes. This review contributes valuable insight to support the complex cell and molecular mechanisms behind the aseptic loosening theories of orthopedic implants.
Bendamustine impairs humoral but not cellular immunity to SARS-CoV-2 vaccination in rituximab-treated B-cell lymphoma–affected patients
Authors: Vanni Anna , Salvati Lorenzo , Mazzoni Alessio , Lamacchia Giulia , Capone Manuela , Francalanci Stefania , Kiros Seble Tekle , Cosmi Lorenzo , Puccini Benedetta , Ciceri Manuel , Sordi Benedetta , Rossolini Gian Maria , Annunziato Francesco , Maggi Laura , Liotta Francesco
Published: December 2023

Background

Patients with B-cell lymphoma are a fragile category of subjects, particularly exposed to infections and characterized by an impaired vaccination response due to the disease itself and, even more, to the chemotherapy regimen. For this reason, extensive knowledge of the immune response status of these subjects is of fundamental importance to obtain possible indications for a tailored immunization strategy.

Methods

We enrolled two cohorts of patients with B-cell lymphoma under rituximab treatment or 3–24 months after treatment. In all patients, we evaluated both humoral and cellular immunological memory toward SARS-CoV-2, after standard vaccination and upon one booster dose.

Results

We observed no Spike-specific IgG production in patients (n = 25) under anti-CD20 treatment, whereas patients (n = 16) vaccinated after the completion of chemotherapy showed a higher humoral response. Evaluating SARS-CoV-2–specific T-cell response, we found that patients in both cohorts had developed robust cellular immunity after vaccination. Of the 21 patients (51%) that experienced a breakthrough SARS-CoV-2 infection, only six patients developed severe disease. Interestingly, these six patients had all been treated with rituximab plus bendamustine. Notably, we observed that Spike-specific IgG levels in patients treated with rituximab plus bendamustine were absent or lower compared with those in patients treated with rituximab plus other chemotherapy, whereas Spike-specific T-cell response was not different based on chemotherapy regiment.

Discussion

Our results show that, in patients with B-cell lymphoma under rituximab therapy, anti–SARS-CoV-2 mRNA vaccination induces a weak or absent humoral response but a consistent T-cell response. In addition, chemotherapy regimens with bendamustine further reduce patients’ ability to mount a Spike-specific humoral response even after a long time period from chemotherapy discontinuation. These results provide evidence that different chemotherapeutics display different immunosuppressive properties that could be taken in to account in the choice of the right drug regimen for the right patient. Moreover, they question whether immunocompromised patients, particularly those treated with bendamustine, need interventions to improve vaccine-induced immune response.
Treatment and practical considerations of diabetic kidney disease
Authors: Bilen Yara , Almoushref Allaa , Alkwatli Kenda , Osman Omar , Mehdi Ali , Sawaf Hanny
Published: December 2023

Diabetic kidney disease (DKD) is a complication of diabetes that can lead to kidney failure. Over the years, several drugs have been developed to combat this disease. In the early 90s, angiotensin blockade (ACEi and ARBs) was introduced, which revolutionized the treatment of DKD. In recent years, newer drugs such as sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, endothelin antagonists, and mineralocorticoid receptor antagonists (MRA) have shown great promise in reducing albuminuria and protecting the kidneys. These drugs are being used in combination with lifestyle modifications, patient education, and risk factor modification to effectively manage DKD. In this review, we will explore the latest pharmacological options, their efficacy, and their potential to revolutionize the management of this debilitating disease.