bluuebunny/crossref_metadata_2025 huggingface dataset:
Laboratório Flora Medicinal: marco no estudo das plantas medicinais brasileiras
Authors: Alves L. F.
Published: August 2022

As plantas medicinais têm sido usadas pelos seres humanos desde a pré-história e 80% da população mundial dependem delas para suprir as suas necessidades básicas de saúde. O mercado mundial de fitoterápicos envolve US$ 40 bilhões anuais. O Brasil tem pelo menos três razões para participar desse mercado. O primeiro é a sua imensa biodiversidade; a segunda, a sua história e a terceira a capacidade técnico-científica de seus cientistas.O Laboratório da Flora Medicinal, fundado no Rio de Janeiro em 1912, desempenhou um papel fundamental no estudo e na comercialização dessas plantas. Durante 20 anos, a Revista da Flora Medicinal, publicou mais de 400 artigos descrevendo mais de 600 plantas medicinais brasileiras.
Comentários sobre o Registro de Fitoterápicos
Authors: Netto E.M. , Shuqair N.S.M.S.A.Q. , Balbino E.E. , Carvalho A.C.B.
Published: August 2022

Fitoterápico é o medicamento obtido empregando-se exclusivamente derivados de droga vegetal como constituintes ativos, caracterizado pelo conhecimento da eficácia e dos riscos de seu uso, assim como pela constância de sua qualidade. A eficácia e segurança podem ser validadas através de levantamentos etnofarmacológicos de utilização, publicações tecnocientíficas ou estudos farmacológicos e toxicológicos pré-clínicos e clínicos. A segurança também é determinada pelos ensaios que comprovam a identidade da planta e a ausência de contaminantes. A qualidade deve ser alcançada mediante o controle das matérias-primas, do produto acabado, materiais de embalagem, formulação farmacêutica e estudos de estabilidade. Este artigo descreve alguns tópicos do registro de fitoterápicos junto à Agência Nacional de Vigilância Sanitária (ANVISA), órgão brasileiro que regula e registra medicamentos.
A New Proposal for Live Load Distribution Factors of Bridges with Transverse Beams
Authors: Abrishamkar Mohammad Bagher , Kholghi Reza , Maleki Shervin
Published: August 2022

Many bridge superstructures use transverse beams as load carrying components. In these systems, usually the transverse beams are connected to the main longitudinal girders or trusses on the two sides of the bridge. Such systems are commonly used in plate girder, box girder, cable-stayed and truss bridges.  The live load distribution factor (LLDF) for bridge superstructures with transverse beams in AASHTO-LRFD bridge design specification has remained unchanged for decades and is prescribed as a function of the distance between the transverse beams. However, for slab-beam superstructures in which longitudinal beams at close spacing carry the loads to the substructure, the LLDFs have gone through many changes throughout the years and in their current forms depend on many parameters such as concrete slab thickness, beam span, longitudinal beam stiffness as well as the distance between the longitudinal beams. This study investigates the factors affecting the LLDF for transverse beams and intends to obtain new equations similar to AASHTO’s longitudinal beam equations. For this purpose, 3D finite element models of different sample bridges were developed and critical parameters affecting the LLDF were identified and varied. Accordingly, the LLDFs for moment and shear forces of transverse beams were obtained through regression analyses. The proposed equations have less than 3.1% of average error for the cases considered.
TEKANAN GEMPA BUMI DAN PANDEMI COVID-19 TERHADAP KETAHANAN FISKAL APBD KABUPATEN LOMBOK UTARA TAHUN 2018－2020
Authors: Sugiri Dani , Firdausyia Anita Kemala
Published: August 2022

Penelitian ini memiliki tujuan mengetahui pengaruh tekanan berupa gempa bumi 2018 dan pandemi Covid-19 terhadap ketahanan fiskal APBD Kabupaten Lombok Utara (KLU) Tahun 2018－2020 yang diukur menggunakan metode pengukuran rasio kinerja keuangan, meliputi rasio derajat desentralisasi fiskal (DDF), rasio tingkat kemandirian, dan rasio tingkat ketergantungan. Penelitian dilakukan dengan metode kualitatif dan menggunakan data primer dan sekunder yang terdiri dari LKPD audited dan/atau semisalnya dari tahun 2018-2020, data anggaran kerugian akibat gempa bumi 2018, data anggaran pemulihan pascagempa 2018, dan data anggaran pemulihan pandemi Covid-19. Data primer diperoleh melalui wawancara dan studi lapangan, sedangkan data sekunder diperoleh melalui studi pustaka dan dokumentasi. Penelitian ini menunjukkan bahwa tekanan berupa gempa bumi 2018 dan pandemi Covid-19 berpengaruh terhadap pelaksanaan pemerintahan pada Pemda KLU selama tahun 2018－2020, dilihat dari fluktuasi dengan kecenderungan penurunan yang terjadi pada berbagai komponen dan subkomponen APBD baik pendapatan, belanja, maupun pembiayaan yang menyebabkan terhambatnya penyelenggaraan fungsi pemerintahan. Berdasarkan hasil pengukuran kinerja keuangan menggunakan derajat desentralisasi fiskal (DDF), rasio tingkat kemandirian, dan rasio tingkat ketergantungan diketahui bahwa ketahanan APBD KLU selama tahun 2018－2020 berturut-turut sebesar 13,64% dengan kriteria kurang, 20,19% dengan kriteria cukup, dan 42,03% dengan kriteria tinggi.
Sosialisasi Pendidikan Karakter serta Kepribadian Kepemimpinan Remaja Berbasis Budaya Lokal di SMTK se-Kabupaten Sumba Barat Daya
Authors: Baun Soleman , Noach Yuvine Marlene Cicilia , Se’u Windynia Givens Giliary
Published: August 2022

Remaja perlu mendapat penguatan pendidikan karakter melalui edukasi dalam kehidupan sehari-hari sehingga mampu mengamalkan nilai karakter yakni nilai nasionalis, religius, gotong royong, mandiri, dan integritas. Ada fenomena yang muncul terkait pelanggaran karakter cukup mengkhawatirkan, contohnya tindak kekerasan, pelanggaram Hak Asasi Manusia (HAM), seks bebas, indisipliner, anarkisme, korupsi, pencurian, ketidakjujuran, dan sebagainya. Untuk itu kita membutuhkan solusi salah satunya yaitu penguatan pendidikan karakter berbasis budaya berkearifan lokal yang dilakukan secara bertahap melalui sosialisasi dimana remaja itu berada. Pendidikan karakter memiliki peran sebagai motor penggerak yang mengusung kaidah, norma yang baik untuk di praktekkan dalam kehidupan sehari-hari. Kegiatan ini dilaksanakn di SMTK Bina Tana Tambolaka, Sumba Barat Daya selama 2 hari yakni 27-28 Mei 2022, dengan peserta berjumlah 40 peserta didik. Hasil sosialisasi menunjukkan adanya peningkatan wawasan dan pemahaman tentang pendidikan karakter dan pengenalan akan potensi diri dan melatih jiwa kepemimpinan. Hal ini terlihat dari dengan keaktifan dan semangat yang tinggi dari peserta selama dua hari dengan tingkat kebermanfaatan ada di nilai rata-rata 3,75, selain itu dukungan positif dari pihak kepala sekolah dan tenaga pendidik menjadi elemen penting dari kegiatan ini.
Pelatihan Pembelajaran Matematika Berbasis Android untuk Memecahkan Masalah Matematika Pada MGMP Matematika Kabupaten Muaro Jambi
Authors: Yurinanda Sherli , Rozi Syamsyida , Multahadah Cut
Published: August 2022

Program pengabdian kepada masyarakat (PPM) merupakan salah satu wujud dari Tridharma Perguruan Tinggi. Berdasarkan hasil observasi,  Guru MGMP Matematika Wil IV Kab. Muaro Jambi  yang menjumpai siswa lebih dominan menggunakan android untuk bermain. Pada kenyataannya android dapat dimanfaatkan sebagai media untuk belajar matematika agar lebih mudah salah satunya melalui aplikasi yaitu Mathway versi Web. Untuk itu Tema PPM ini yaitu Pelatihan Pembelajaran Matematika Berbasis Android untuk Memecahkan Masalah Matematika di Bidang Aljabar Pada MGMP Matematika Kab. Muaro Jambi. Kegiatan ini  dilakukan secara daring melalui platform ZOOM. Metode pelaksanaannya berupa pendekatan tentang rencana program dan pelaksanaan. PPM ini dilaksanakan tanggal 27 November 2021 dengan jumah peserta 25 orang. Setelah melaksanakan kegiatan PPM ini,  para peserta yang berpartisipasi sangat antusias dan 95% peserta pelatihan merasa software berbasis android lebih mudah diperoleh, diaplikasikan serta bisa membantu memahami pelajaran di sekolah.
Peningkatan Kapasitas Pengetahuan dan Keterampilan Siswa dalam Bidang Penginderaan Jauh dan Sistem Informasi Geografi untuk Siswa SMA Inklusi
Authors: Sari Dewi Novita , Wibowo Afif Ari , Anggani Nirma Lila , Kiat Umar El Izzudin
Published: August 2022

Perkembangan teknologi melahirkan revolusi industri 4.0 memberikan dampak signifikan di dunia pendidikan. Keterbatasan alat dan media pembelajaran berbasis teknologi di SMA menyebabkan pengetahuan dan keterampilan siswa menguasai perkembangan teknologi terbarukan masih dinilai cukup terbatas. Penginderaan Jauh dan Sistem Informasi Geografis (SIG) adalah salah satu cabang studi geografi yang memanfaatkan teknologi berbasis komputer untuk dapat mengidentifikasi, memvisualisasi, dan menganalisis data kenampakan permukaan bumi. Tujuan kegiatan untuk meningkatkan pengetahuan dan keterampilan siswa sekolah inkluasi SMA Muhammadiyah 6 Surakarta di bidang penginderaan jauh dan SIG serta mengetahui teknik pembelajaran yang tepat untuk anak berkebutuhan khusus (ABK). Mitra kegiatan adalah SMA Muhammadiyah 6 Surakarta yang merupakan salah satu sekolah inklusi di Surakarta. Tahapan peningkatan kapasitas siswa dilakukan dengan cara lokakarya dengan urutan perencanaan, pelaksanaan, dan evaluasi. Hasil yang diperoleh adalah meningkatnya kapasitas pengetahuan dan keterampilan siswa dibuktikan dengan metode pre-test dan post-test dalam hal pembelajaran kontekstual, keterampilan, integritas diri dan komunikasi, serta minat belajar.
Fabrication of Ginsenoside-Based Nanodrugs for Enhanced Antitumor Efficacy on Triple-Negative Breast Cancer
Authors: Zuo Shuting , Wang Jing , An Xianquan , Wang Zhenyu , Zheng Xiao , Zhang Yan
Published: August 2022

There is an urgent need to identify chemotherapeutic agents with improved efficacy and safety against triple-negative breast cancer (TNBC). Ginsenosides can reportedly induce tumor cell death, invasion, and metastasis; however, poor water solubility, low oral absorption rate, and rapid blood clearance limit their clinical application. Utilizing the amphiphilic property of ginsenosides as building blocks of biomaterials, we fabricated a carrier-free nanodrug composed of ginsenosides Rg3 and Rb1 using a nano-reprecipitation method without any additional carriers. After characterizing and demonstrating their uniform morphology and pH-sensitive drug release properties, we observed that Rg3-Rb1 nanoparticles (NPs) exhibited stronger antitumor and anti-invasive effects on TNBCs in vitro than those mediated by free ginsenosides. Consequently, Rg3-Rb1 NPs afforded superior inhibition of tumor growth and reduction of pulmonary metastasis than the Rg3 and Rb1 mixture, with no obvious systematic toxicity in vivo. Collectively, our results provide a proof-of-concept that self-assembled engineered ginsenoside nanodrugs may be efficient and safe for TNBC therapy.
Role and Clinical Application of Metagenomic Next-Generation Sequencing in Immunocompromised Patients With Acute Respiratory Failure During Veno-Venous Extracorporeal Membrane Oxygenation
Authors: Zhao Yang-Chao , Ding Yan-Zhong , Zhao Xi , Fu Guo-Wei , Huang Ming-Jun , Li Xing-Xing , Sun Qian-Qian , Kan Ya-Bai , Li Jun , Wang Shi-Lei , Ma Wen-Tao , Xu Qin-Fu , Liu Qi-Long , Li Hong-Bin
Published: August 2022

Objectives

There are few studies of metagenomic next-generation sequencing (mNGS) in immunocompromised patients assisted by veno-venous extracorporeal membrane oxygenation (vv-ECMO). The present study is aimed to investigate the pathogen-detected effect and clinical therapy value of mNGS technologies in immunocompromised patients assisted by vv-ECMO.

Methods

Our study retrospectively enrolled 46 immunocompromised patients supported by vv-ECMO from Jan 2017 to June 2021 at the First Affiliated Hospital of Zhengzhou University, respectively. Patients were divided into the deterioration group (Group D) (n = 31) and improvement group (Group I) (n = 15) according to their outcomes. Baseline characteristics and etiological data of patients during hospitalization of 2 groups were compared. The pathogens detected by mNGS and antibiotic regimens guided by mNGS in immunocompromised patients assisted by vv-ECMO were analyzed.

Results

Compared with Group I, the deterioration patients showed a higher percentage of chronic obstructive pulmonary disease (COPD) (32.3% vs. 6.7%, p < 0.01) and were significantly older (47.77 ± 16.72 years vs. 32 ± 15.05 years, p < 0.01). Within 48 h of being ECMO assisted, the consistency of the samples detected by traditional culture and mNGS at the same time was good (traditional culture vs. mNGS detection, the positive rate of bronchoalveolar lavage fluid (BALF) culture: 26.1% vs. 30.4%; the positive rate of blood sample culture: 12.2% vs. 12.2%, p > 0.05). However, mNGS detected far more pathogen species and strains than conventional culture (30 strains vs. 78 strains, p < 0.01); the most popular pathogen was Klebsiella pneumoniae. Parts of patients had their antibiotic treatment adjustments, and the improvement patients showed less usage of broad-spectrum antibiotics.

Conclusions

mNGS may play a relatively important role in detecting mixed pathogens and personalized antibiotic treatment in immunocompromised patients assisted by vv-ECMO.
Leishmania guyanensis suppressed inducible nitric oxide synthase provoked by its viral endosymbiont
Authors: Kopelyanskiy Dmitry , Desponds Chantal , Prevel Florence , Rossi Matteo , Migliorini Romain , Snäkä Tiia , Eren Remzi Onur , Claudinot Stéphanie , Lye Lon-Fye , Pasparakis Manolis , Beverley Stephen M. , Fasel Nicolas
Published: August 2022

Inducible nitric oxide synthase (iNOS) is essential to the production of nitric oxide (NO), an efficient effector molecule against intracellular human pathogens such as Leishmania protozoan parasites. Some strains of Leishmania are known to bear a viral endosymbiont termed Leishmania RNA virus 1 (LRV1). Recognition of LRV1 by the innate immune sensor Toll-like receptor-3 (TLR3) leads to conditions worsening the disease severity in mice. This process is governed by type I interferon (type I IFNs) arising downstream of TLR3 stimulation and favoring the formation of secondary metastatic lesions. The formation of these lesions is mediated by the inflammatory cytokine IL-17A and occurs in the absence, or low level of, protective cytokine IFN-γ. Here, we described that the presence of LRV1 led to the initial expression of iNOS and low production of NO that failed to control infection. We subsequently showed that LRV1-triggered type I IFN was essential but insufficient to induce robust iNOS induction, which requires strong activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Leishmania guyanensis carrying LRV1 (LgyLRV1+) parasites mitigated strong iNOS production by limiting NF-kB activation via the induction of tumor necrosis factor-alpha-induced protein 3 (TNFAIP3), also known as A20. Moreover, our data suggested that production of LRV1-induced iNOS could be correlated with parasite dissemination and metastasis via elevated secretion of IL-17A in the draining lymph nodes. Our findings support an additional strategy by which LRV1-bearing Leishmania guyanensis evaded killing by nitric oxide and suggest that low levels of LRV1-induced NO might contribute to parasite metastasis.
Institutional and Academic Transcripts of Police Interrogations
Authors: Komter Martha
Published: August 2022

The effects of working circumstances and intended uses on the transcripts of police interrogations cannot be underestimated. In the Netherlands, police transcripts are usually drawn up in the course of the interrogation by the interrogator or, when two police officers conduct the interrogation, by the reporting officer. Contemporaneous transcription involves the interrogators in a complex configuration of interactional commitments. They have to find a way to coordinate the talk and the typing, they must transcribe the talk of an event they themselves participate in, they must do justice to the suspects' story while also taking into account the intended readership of the police report, and they must produce a document that can serve as an official piece of evidence in the criminal case. In studying recorded police interrogations and their transcripts I realised that my own transcripts are also related to their intended uses and to my working circumstances. My transcriptions are much more detailed than those of the police, which draws the attention to the differences between them. The most noticeable difference is that police transcripts focus on substance and mine on interaction. Police transcripts are meant to be evidence of the offence and mine of the talk. But there are also similarities. Both police transcripts and those of mine are selective. Police transcripts orient to their relevance for building a case, mine orient to their relevance for my research questions. Both police transcripts and those of mine treat the transcript as the talk it is meant to represent. For a criminal case this means that in court suspects are held accountable for what the police wrote down as their statement, which disregards the fact that the police transcript is a coproduction.
Relationship between lifestyle and metabolic factors and carotid atherosclerosis: A survey of 47,063 fatty and non-fatty liver patients in China
Authors: Zhang Chun , Wang Jiangang , Ding Siqing , Gan Gang , Li Lijun , Li Ying , Chen Zhiheng , Duan Yinglong , Xie Jianfei , Cheng Andy S. K.
Published: August 2022

Background and aims

Carotid atherosclerosis and stenosis are common lesions of the artery wall that form the basis of cardiovascular events. Compared with coronary atherosclerosis, few studies have explored the influencing factors of carotid atherosclerosis. The aim of this study was to explore the influencing factors of carotid atherosclerosis and carotid stenosis without and with fatty liver disease (FLD).

Methods

A total of 47,063 adults were recruited for this cross-sectional study. The color Doppler ultrasound, including metabolic factors and lifestyle surveys, was used to determine whether the participants had FLD and carotid artery disease. Multiple logistic regression was used to investigate the influencing factors of lifestyle and metabolism of carotid atherosclerosis and stenosis in the participants with and without FLD.

Results

In participants without FLD, current alcohol consumption (OR: 0.749, 95% CI: 0.588) and hip circumference (OR: 0.970, 95% CI: 0.961, 0.979) were the main protective factors for carotid atherosclerosis. Systolic blood pressure (OR: 1.022, 95% CI: 1.019, 1.025) and diastolic blood pressure (OR: 1.005, 95% CI: 1.001, 1.010), elevated fasting blood glucose (OR: 1.012, 95% CI: 1.005, 1.019), and non-sedentary behavior (OR: 1.084, 95% CI: 1.014, 1.160) were the main risk factors for carotid atherosclerosis. Hip circumference (OR: 0.932, 95% CI: 0.910, 0.954) and low-density lipoprotein (OR: 0.979, 95% CI: 0.964, 0.994) were protective factors for carotid stenosis. Smoking (OR: 3.525, 95% CI: 1.113, 11.169) and unqualified exercise (OR: 1.402, 95% CI: 1.083, 1.815) were risk factors for carotid stenosis. In participants with FLD, smoking (OR: 0.827, 95% CI: 0.703, 0.973) and hip circumference (OR: 0.967, 95% CI: 0.958, 0.977) were the main protective factors for carotid atherosclerosis. BMI 18.5–23.9 (OR: 1.163, 95% CI: 1.002, 1.351), non-sedentary behavior (OR: 1.086, 95% CI: 1.009, 1.168), and waist circumference (OR: 1.030, 95% CI: 1.022, 1.038) were the main risk factors for carotid atherosclerosis.

Conclusion

Based on a large-sample check-up population in China, this study investigated the influencing factors of carotid atherosclerosis and carotid stenosis in fatty liver and non-fatty liver patients and explored the influencing factors of metabolism and lifestyle, which were mainly focused on exercise, sedentary behavior, smoking, alcohol consumption, hip circumference, and blood pressure.
Hallermann–Streiff syndrome: Case report with abnormal pulp calcifications
Authors: Ammar Nour , El-Tekeya Magda M.
Published: August 2022

Hallermann–Streiff syndrome (HSS) is a disorder of rare occurrence affecting the craniofacial complex, with approximately 200 cases reported in the literature. Nonetheless, its distinctive facial features render it highly recognizable. We present the case of a 5-year-old girl with this syndrome and review the dental manifestations and management in this patient. In addition to the diagnostic facial features of brachycephaly with frontal bossing, beak-shaped nose, microphthalmia, and mandibular retrusion, multiple dental manifestations were noted, including the absence of the mandibular condyle, ghost teeth, and unusual pulpal calcifications in both the primary and the permanent teeth, which have not been previously reported in a case of HSS. There is no consensus on the suitable treatment plan to be given for HSS patients at a young age due to an underreporting of these cases in the literature. In this report, we discuss pediatric dental management options for a patient with HSS and share her perspective on the treatment.
Domain Adaptation on Multiple Cloud Recognition From Different Types of Meteorological Satellite
Authors: Huang Bin , Xiao Luming , Feng Wen , Xu Mengqiu , Wu Ming , Fang Xiang
Published: August 2022

Meteorological satellites have become an indispensable meteorological tool for earth observation, as aiding in areas such as cloud detection, which has important guiding significance for maritime activities. However, it is time-consuming and labor-intensive to obtain fine-grained annotations provided by artificial experience or mature satellite cloud products for multi-spectral maritime cloud imageries, especially when new satellites are launched. Moreover, due to the data discrepancy caused by different detection bands, existing models have inadequate generalization performance compared to new satellites, and some cannot be directly migrated. In this paper, to reduce the data distribution’s discrepancy, an approach is presented based on unsupervised domain adaption method for marine cloud detection task based on Himawari-8 satellite data as a source domain and Fengyun-4 satellite data as a target domain. The goal of the proposed method is to leverage the representation power of adversarial learning to extract domain-invariant features, consisting of a segmentation model, a feature extract model for target domain, and a domain discriminator. In addition, aiming to remedy the discrepancy of detection bands, a band mapping module is designed to implement consistency between different bands. The result of the experiments demonstrated the effectiveness of the proposed method with a 7% improvement compared with the comparative experiment. We also designed a series of statistical experiments on different satellite data to further study cloudy perception representation, including data visualization experiment and cloud type statistics.
Students’ learning approaches as a factor of academic achievement at selected public universities: A cross-sectional study
Authors: Negash Tadese Tamire , Eshete Million Tesfaye , Hanago Getu Ataro
Published: August 2022

Introduction

Excellence in anesthesia education has been advocated to meet the current and future needs of society. Universities play a key role in creating a conducive climate for learning and facilitating the development of expected competencies among graduates. This study assessed students’ learning approaches and their relationship with their academic achievement at two selected public universities in Ethiopia.

Materials and methods

A cross-sectional study was conducted on 123 anesthesia students. All 3rd- and 4th-year students were recruited for the study. Study Skills Inventory for Students (ASSIST) was used to assess students’ learning approaches. Perceived performance, cumulative grade point average (cGPA), and 100 MCQ items were used to assess academic achievement. Data were entered into Epi-data and exported to SPSS for statistical analysis. An independent t-test was used to determine the presence of a difference in academic achievement across learning approaches. Bivariate and multivariable linear regressions were fitted to assess the association of students’ characteristics and learning approaches with their academic achievement. A P-value of less than 0.05 was used to declare the statistical significance.

Result

There were no statistically significant differences between the groups on most of the learning approaches and academic achievement measures. In multivariable linear regression, university entrance exam results, students’ perception of the definition of learning, and a deep approach to learning were found to be the predictors of students’ academic achievement (β = 0.004 and P = 0.03, β = 0.14 and P = 0.015, and β = 0.13 and P = 0.023), respectively.

Conclusion

In this study, students mainly follow deep approaches to learning, and there were no statistically significant differences between the groups on most of the learning approach measures and academic achievements. Entrance exam results, positive perception of the definition of learning, and a deep approach to learning were found to be positive predictors of academic achievement. Emphasis has to be given to improving students’ learning approaches for better academic achievement and success.
Effects of GLP-1 receptor agonists on arrhythmias and its subtypes in patients with type 2 diabetes: A systematic review and meta-analysis
Authors: Wei Jinjing , Wang Ruxin , Ye Haowen , Wang Ying , Wang Lihong , Zhang Xiaofang
Published: August 2022

Purpose

An update of a systematic review and meta-analysis of the risk of arrhythmias and their subtypes in type 2 diabetic patients receiving glucagon-like peptide 1 receptor agonist (GLP-1RA) medication according to data from the Cardiovascular Outcome Trial(CVOT).

Methods

Randomized controlled trials (RCT) on GLP-1RA therapy and cardiovascular outcomes in type 2 diabetes mellitus patients published in full-text journal databases such as MEDLINE (via PubMed), Embase, Clinical Trials.gov, and the Cochrane Library from establishment to March 1, 2022 were searched. We assessed the quality of individual studies by the Cochrane risk-of-bias algorithm. RevMan 5.4.1 software was use for calculating meta-analysis.

Results

A total of 60,081 randomized participants were included in the data of these 8 GLP-1RA cardiovascular outcomes trials. Pooled analysis reported no significant effect on total arrhythmia [RR=0.96, 95% CI (0.96, 1.05), p =0.36], and its subtypes such as atrial fibrillation [RR=0.96, 95% CI (0.86, 1.07), p =0.43], atrial flutter [RR= 0.82, 95% CI (0.57, 1.19), p =0.30], atrial tachycardia [RR=0.64, 95% CI (0.20, 2.01), p =0.44)], sinoatrial node dysfunction [RR=0.74, 95% CI (0.44, 1.25), p =0.26], ventricular preterm systole [RR=1.42, 95% CI (0.62, 3.26), p =0.41], second degree AV block [RR=0.96, 95% CI (0.53, 1.72), p =0.88], complete AV block [RR=0.75, 95% CI (0.49, 1.17), p =0.21], ventricular fibrillation [RR=1.00, 95% CI (0.50, 2.02), p =1.00], ventricular tachycardia [RR=1.37, 95% CI (0.91, 2.08), p =0.13] from treatment with GLP-1RA versus placebo. However, the risk of hypoglycemia was reduced by about 30% [RR=0.70, 95% CI (0.57, 0.87), p=0.001] and the risk of pneumonia by about 25% [RR=0.85, 95% CI (0.75, 0.97), p=0.01], both statistically significant differences.

Conclusion

In type 2 diabetic patients, treatment with GLP-1RA has no significant effect on the risk of major arrhythmias but significantly reduces the risk of hypoglycemia and pneumonia.
Prolonged proximity to humans ensures better performance of semi-captive Asian elephants at discriminating between human individuals by voice
Authors: Li Li-Li , He Ruchuan , Pansini Riccardo , Quan Rui-Chang
Published: August 2022

To avoid risks, organisms must recognize threatening heterospecies from non-threatening onesviaacoustic cues from a distance. With land-use change, humans have encroached considerably into natural areas. Therefore, it is beneficial to animals to use acoustic cues to discriminate between different levels of threats posed by humans. Our study aims at testing this discriminatory ability in Asian elephants (Elephas maximus), animals that have been for long history subjected to human interaction. We tested whether eighteen semi-captive elephants could discriminate between voices of their own mahouts (i.e., who take care of the elephants exclusively) and of other mahouts (unfamiliar individuals). The results showed that elephants responded successfully to the commands from their own mahouts, with an average response rate as high as 78.8%. The more years the mahouts had been as their caretakers, the more the elephant showed active responses toward the commands. Female elephants responded to the commands more frequently and faster than males. Also younger elephants responded more frequently and faster than older elephants. We argue that Asian elephants can discriminate between familiar and unfamiliar humans by acoustic cues alone. Proximity with humans may be a factor, as fundamental as domestication, for animals to develop heterospecies discriminatory ability.
Harvesting Intensity and Aridity Are More Important Than Climate Change in Affecting Future Carbon Stocks of Douglas-Fir Forests
Authors: Robinson Alyssa J. , Defrenne Camille E. , Roach W. Jean , Dymond Caren C. , Pickles Brian J. , Simard Suzanne W.
Published: August 2022

Improved forest management may offer climate mitigation needed to hold warming to below 2°C. However, uncertainties persist about the effects of harvesting intensity on forest carbon sequestration, especially when considering interactions with regional climate and climate change. Here, we investigated the combined effects of harvesting intensity, climatic aridity, and climate change on carbon stocks in Douglas-fir [Pseudotsuga menziesii Mirb. (Franco)] stands. We used the Carbon Budget Model of the Canadian Forest Sector to simulate the harvest and regrowth of seven Douglas-fir stand types covering a 900 km-long climate gradient across British Columbia, Canada. In particular, we simulated stand growth under three regimes (+17%, −17% and historical growth increment) and used three temperature regimes [historical, representative concentration pathways (RCP) 2.6 and RCP 8.5]. Increasing harvesting intensity led to significant losses in total ecosystem carbon stocks 50 years post-harvest. Specifically, forests that underwent clearcutting were projected to stock about 36% less carbon by 2,069 than forests that were left untouched. Belowground carbon stocks 50 years into the future were less sensitive to harvesting intensity than aboveground carbon stocks and carbon losses were greater in arid interior Douglas-fir forests than in humid, more productive forests. In addition, growth multipliers and decay due to the RCP’s had little effect on total ecosystem carbon, but aboveground carbon declined by 7% (95% confidence interval [−10.98, −1.81]) in the high emissions (RCP8.5) scenario. We call attention to the implementation of low intensity harvesting systems to preserve aboveground forest carbon stocks until we have a more complete understanding of the impacts of climate change on British Columbia’s forests.
The miR166–mRNA network regulates vascular tissue differentiation in Moso bamboo
Authors: Li Ying , Zhang Shuqin , Zhang Deqiang , Li Xueping , Gao Zhimin , Jiang Zehui
Published: August 2022

miR166s play an important role in plant tissue differentiation. However, the functions of miR166s in the differentiation of vascular tissue in bamboo have not yet been elucidated. Here, we showed that five miR166s are overexpressed (tags per million reads > 2,000) in underground shoot samples of wild-type (WT) Moso bamboo (Phyllostachys edulis) and a thick-walled variant (P. edulis “Pachyloen”) throughout the developmental process. Potential targets of these miR166s include some genes encoding homeodomain-leucine zipper (HD-ZIP) transcription factors and protein kinases. Cleavage sites for miR166s were identified in seven PeHD-ZIP homologs and a protein kinase gene via degradome sequencing (p < 0.05). Dual-luciferase and transient expression assays confirmed the binding of miR166s to PeHOXs. Fluorescence in situ hybridization revealed that miR166s were localized to the xylem of the leaf, root, and internode of 2-month-old pot seedlings of WT Moso bamboo. Overall, these findings reveal that miR166s are regulators of vascular tissue differentiation in bamboo. The miR166s identified in our study provide novel targets for bamboo breeding.
Current and future aspects of IBD research and treatment: The 2022 perspective
Authors: Stange Eduard F.
Published: August 2022

Inflammatory bowel diseases (IBD) have seen major progress in current concepts and treatment regimes. Based on the theory of an inadequate “overshoot” of the mucosal immune response to the intestinal microbiome, therapies have been developed to interfere with the key mediators of inflammation from cytokines, including TNF and IL12/23, to integrins such as α4ß7 and intracellular cytokine signal transducers such as janus kinases. Recently, sphingosine-1-receptor agonists were marketed to suppress mucosal inflammation by sequestering lymphocytes in peripheral lymph nodes. However, the aim of these regimes targeting immunity to induce a long-term deep remission, including mucosal healing, is missed in most patients. Contrasting these anti-inflammatory mechanisms of action, the pathogenic focus has finally shifted to the mucosal antibacterial barrier in both Crohn´s disease and ulcerative colitis. Translating this novel concept requires a completely different approach but, in the end, may come closer to a cure of these devastating diseases, in which an incomplete immune modulation fails to achieve the key endpoints: halting disease activity and progression. This review aims to give an overview of past, current, and future concepts in IBD, focusing on both pathogenesis and consequent therapy. A cure is in sight only if both reflect the actual key mechanisms of slow bacterial entry into the mucosa and are harmonized and in line.
Antiviral activity of extracellular vesicles derived from respiratory syncytial virus-infected airway epithelial cells
Authors: Corsello Tiziana , Qu Yue , Ivanciuc Teodora , Garofalo Roberto P. , Casola Antonella
Published: August 2022

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infections in children and elderly. No vaccine or effective treatment is currently available for RSV. Extracellular vesicles (EVs) are microvesicles known to carry biologically active molecules, including RNA, DNA and proteins (i.e. cargo). Viral infections can induce profound changes in EV cargo, and the cargo can modulate cellular responses of recipient cells. We have recently shown that EVs isolated from RSV-infected cells were able to activate innate immune response by inducing cytokine and chemokine release from human monocytes and airway epithelial cells, however, we did not investigate the potential antiviral contribution of EVs to a subsequent infection. The objective of this study was to assess the presence of innate immune mediators, including type I and III interferons (IFNs) in EVs released from airway epithelial cells infected with RSV, and their potential role in modulating viral replication in recipient cells. EV-derived from cells infected with RSV were associated with significant amounts of cytokine and chemokines, as well as IFN-β and -λ, compared to EVs isolated from mock-infected cells. Cells treated with RSV-EVs showed significantly lower levels of viral replication compared to untreated or mock-EV-treated RSV infected cells. Cellular pretreatment with Cerdulatinib, an IFN receptor signaling inhibitor, inhibited the antiviral activity of RSV-EVs in recipient airway epithelial cells. Furthermore, treatment of A549 cells with RSV-EVs induced the expression of IFN-dependent antiviral genes, supporting the idea that RSV-EVs exerts their antiviral activity through an interferon-dependent mechanism. Finally, we determined the concentrations of soluble and EV-associated IFN-β and IFN-λ in five nasopharyngeal secretions (NPS) of children with viral infections. There were significant levels of IFN-λ in NPS and NPS-derived EVs, while IFN-β was not detected in either of the two types of samples. EVs released from RSV-infected cells could represent a potential therapeutic approach for modulating RSV replication in the airways.
Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes mellitus
Authors: He Lina , Chen Rongping , Zhang Bangzhou , Zhang Shuo , Khan Barkat Ali , Zhu Dan , Wu Zezhen , Xiao Chuanxing , Chen Baolong , Chen Fengwu , Hou Kaijian
Published: August 2022

Type 1 diabetes mellitus (T1DM) is an autoimmune-mediated disease characterized by a reduced or absolute lack of insulin secretion and often associated with a range of vascular and neurological complications for which there is a lack of effective treatment other than lifestyle interventions and pharmacological treatments such as insulin injections. Studies have shown that the gut microbiota is involved in mediating the onset and development of many fecal and extrafecal diseases, including autoimmune T1DM. In recent years, many cases of gut microbiota transplantation for diseases of the bowel and beyond have been reported worldwide, and this approach has been shown to be safe and effective. Here, we conducted an experimental treatment study in two adolescent patients diagnosed with autoimmune T1DM for one year. Patients received one to three rounds of normal fecal microbiota transplants (FMT) and were followed for up to 30 weeks. Clinical outcomes were measured, including biochemical indices, medication regimen, and dosage adjustment. Fecal microbiota metagenomic sequencing after transplantation provides a reference for more reasonable and effective microbiota transplantation protocols to treat autoimmune T1DM. Our results suggest that FMT is an effective treatment for autoimmune T1DM.

Clinical Trial Registration

http://www.chictr.org.cn, identifier ChiCTR2100045789.
Papain-like protease of SARS-CoV-2 inhibits RLR signaling in a deubiquitination-dependent and deubiquitination-independent manner
Authors: Ran Xiang-Hong , Zhu Jia-Wu , Chen Ya-Yun , Ni Run-Ze , Mu Dan
Published: August 2022

The newly emerged severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) can result in dysregulated interferon (IFN) responses that contribute to disease severity. The papain-like protease of SARS-CoV-2 (SCoV2-PLpro) has been previously reported to attenuate IFN responses, but the underlying mechanism is not fully understood. In this study, we found that SCoV2-PLpro potently suppressed IFN production and signaling induced by Sendai virus as well as RIG-I-like receptor (RLR) signaling pathway components, including RIG-I, MAVS, TBK1, TRAF3, TRAF6, and IRF3. SCoV2-PLpro exhibited different specificity and efficiency than SARS-CoV PLpro, with the former exerting a greater inhibitory effect on the RIG-I- and TRAF3-mediated IFN response but a weaker effect on the MAVS-mediated IFN response. Furthermore, we showed that SCoV2-PLpro significantly reduced K63-ubiquitination of RIG-I, MAVS, TBK1, TRAF3, TRAF6, and IRF3 and K48-ubiquitination of IκBα, which are known critical for the innate immune signal transduction. The deubiquitinating (DUB) activity of SCoV2-PLpro required a catalytic residue cysteine 111 (C111) but not the UBL domain. Notably, by utilizing the DUB-defective C111 mutant, we demonstrated that SCoV2-PLpro targeted RLR signaling pathway regulators via deubiquitination-dependent and -independent mechanisms, with the inhibitory activities of RIG-I and TBK1 correlating with DUB function, whereas the antagonism effects on MAVS, TRAF3, TRAF6, and IRF3 independent on DUB activity. Overall, our results reveal that SCoV2-PLpro evolves differential IFN antagonism activity from SCoV1-PLpro and it targets multiple key RLR signaling pathway components via various mechanisms, providing insights into SARS-CoV-2 pathogenesis and clues for developing antiviral therapies for COVID-19.
Metabolomics in rheumatoid arthritis: Advances and review
Authors: Xu Lingxia , Chang Cen , Jiang Ping , Wei Kai , Zhang Runrun , Jin Yehua , Zhao Jianan , Xu Linshuai , Shi Yiming , Guo Shicheng , He Dongyi
Published: August 2022

Rheumatoid arthritis (RA) is an autoimmune disease accompanied by metabolic alterations. The metabolic profiles of patients with RA can be determined using targeted and non-targeted metabolomics technology. Metabolic changes in glucose, lipid, and amino acid levels are involved in glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway, the arachidonic acid metabolic pathway, and amino acid metabolism. These alterations in metabolic pathways and metabolites can fulfill bio-energetic requirements, promote cell proliferation, drive inflammatory mediator secretion, mediate leukocyte infiltration, induce joint destruction and muscle atrophy, and regulate cell proliferation, which may reflect the etiologies of RA. Differential metabolites can be used as biomarkers for the diagnosis, prognosis, and risk prediction, improving the specificity and accuracy of diagnostics and prognosis prediction. Additionally, metabolic changes associated with therapeutic responses can improve the understanding of drug mechanism. Metabolic homeostasis and regulation are new therapeutic strategies for RA. In this review, we provide a comprehensive overview of advances in metabolomics for RA.
Host-microbiota interactions: The aryl hydrocarbon receptor in the acute and chronic phases of cerebral ischemia
Authors: Fan Xuemei , Wang Shuai , Hu Shuqi , Yang Bingjie , Zhang Hao
Published: August 2022

The relationship between gut microbiota and brain function has been studied intensively in recent years, and gut microbiota has been linked to a couple of neurological disorders including stroke. There are multiple studies linking gut microbiota to stroke in the “microbiota-gut-brain” axis. The aryl hydrocarbon receptor (AHR) is an important mediator of acute ischemic damage and can result in subsequent neuroinflammation. AHR can affect these responses by sensing microbiota metabolites especially tryptophan metabolites and is engaged in the regulation of acute ischemic brain injury and chronic neuroinflammation after stroke. As an important regulator in the “microbiota-gut-brain” axis, AHR has the potential to be used as a new therapeutic target for ischemic stroke treatment. In this review, we discuss the research progress on AHR regarding its role in ischemic stroke and prospects to be used as a therapeutic target for ischemic stroke treatment, aiming to provide a potential direction for the development of new treatments for ischemic stroke.
A bibliometric and scientific knowledge-map study of the chimeric antigen receptor (CAR) natural killer (NK) cell-related research from 2010 to 2022
Authors: Zhang Juan , Chen Peng , Miao Lele
Published: August 2022

Objectives

As emerging adoptive immunotherapy after CAR-T cell therapy, CAR-NK cell therapy has been developing rapidly in recent years. Presently, the research on CAR-NK cells has become a hotspot in the field of tumor immunotherapy.

Methods

In this descriptive study, CtieSpace and VOSviewer were used to perform the bibliometric and scientific knowledge-map analysis of articles and reviews related to CAR-NK cells.

Results

5371 authors from 715 institutions in 65 countries published 1028 papers about CAR-NK cells in 346 journals. The number of publications related to CAR-NK cells was increasing overall, especially from 2018 to 2021. The United States was in a leading position. The most active institution was Univ Texas, MD Anderson Cancer Center (USA). The journal with the most publications was Frontiers in immunology, and the most co-cited journal was Blood. The researcher with the most published papers was Winfried S. Wels, while the most co-cited researcher was Shannon L Maude. The research of CAR-NK cells in hematological malignancies and solid tumors (especially the selection of targets and the evaluation of efficacy and safety) was a research hotspot in this field. The emerging topics mainly included three aspects. First, further improve the proliferation and persistence of NK cells in vivo. Secondly, optimizing and improving the CAR structure for NK cells to improve the anti-tumor ability of CAR-NK cells. Thirdly, the related research of CRISPR/Cas9 gene-editing technology in constructing engineered immune cells.

Conclusion

In this study, a bibliometric and scientific knowledge-map study provided a unique and objective perspective for the CAR-NK cell field. This information would provide a helpful reference for researchers interested in this field.
Tolerant but facing increased competition: Arctic zooplankton versus Atlantic invaders in a warming ocean
Authors: Kaiser Patricia , Hagen Wilhelm , Bode-Dalby Maya , Auel Holger
Published: August 2022

The Arctic Ocean is rapidly changing. Air temperature is rising two to four times faster in the Arctic than the global average, with dramatic consequences for the ecosystems. Polar zooplankton species have to cope with those increasing temperatures, whilst simultaneously facing increasing competition by boreal-Atlantic sister species advected into the Arctic Ocean via a stronger Atlantic inflow. To assess the sensitivity of Arctic and Atlantic zooplankton to rising temperatures, respiration rates of dominant Arctic species (Calanus hyperboreus, Calanus glacialis, Paraeuchaeta glacialis, Themisto libellula) and their co-occurring Atlantic congeners (Calanus finmarchicus, Paraeuchaeta norvegica, Themisto abyssorum) were measured at ambient temperatures and simulated conditions of ocean warming from 0 to 10°C during three expeditions with RV Polarstern to the Arctic Fram Strait. Arctic zooplankton showed only slowly increasing respiration rates with increasing temperatures, also indicated by low Q10 ratios. In contrast, boreal-Atlantic representatives responded to higher temperatures by a rapid and steeper increase in their respiration rates (higher Q10), suggesting higher metabolic activity. These results imply that Arctic species are physiologically more tolerant to ocean warming than expected but might be outcompeted by their Atlantic congeners beyond a certain temperature threshold in areas of strong distribution overlap. Thus, the ‘Atlantification’ of the Arctic zooplankton community seems to be driven rather by ecological interactions than by physiological limitations. Changes in zooplankton community composition and biodiversity will have major consequences for trophodynamics and energy flux in Arctic ecosystems, since polar species tend to be larger than their southern counterparts and have a higher lipid content, providing more energy-rich food for higher trophic levels.