bluuebunny/crossref_metadata_2025 huggingface dataset:
Motif Penggunaan Video Broadcasting pada Sistem Pembelajaran Online
Authors: Sirait Yohanes Lumban , Kurnia Kurnia
Published: August 2022

Tujuan dari penelitian ini untuk memahami persepsi mahasiswa dalam menggunakan Video Broadcasting pada sistem pembelajaran online. Persespsi mahasiswa dipahami sebagai motif penggunaan yang didasarkan pada kegunaan (Perceived usefulness) dan kemudahan (Perceived Ease of Use) penggunaan Video Broadcasting pada sistem pembelajaran. Hasil penelitian menunjukkan bahwa motif penggunaan video broadcasting pada sistem pembelajaran online dipengaruhi oleh kegunaan video broadcasting sebagai sarana pembelajaran dan kemudahan akses video broadcasting tersebut. Khususnya pada kemudahan penggunaan media video broadcasting (Perceived Ease of Use) yang terbukti menjadi faktor yang dominan memotivasi mahasiswa dalam menggunakan video broadcasting. Semakin mudah penggunaan dan akses media video broadcasting maka semakin besar motivasi mahasiswa dalam menggunakan video broadcasting tersebut sebagai sarana pembelajaran online. Persepsi kegunaan (Perceived usefulness) video broadcasting juga menentukan motivasi penggunaan video broadcasting, sehingga artinya semakin besar nilai manfaat atau kegunaan video broadcasting dalam  membantu pemahaman pembelajaran mahasiswa maka semakin tinggi motivasti mahasiswa mengakses video broadcasting. Pada penelitian ini terdapat kekurangan temuan yang cuma terjadi pada objek kajian yaitu STIKOM InterStudi. Maka untuk mendapatkan temuan yang lebih beragam dalam konteks penyiaran, penelitian selanjutnya juga dapat meneliti objek analisis yang berbeda pada kajian studi kasus sejenis.
PENGARUH GAYA BICARA PRESENTER TALKSHOW HITAM PUTIH DI TRANS7 TERHADAP MINAT MENONTON
Authors: Aulia Devi , Prasetyawati Happy
Published: August 2022

Program talkshow menjadi andalan di berbagai stasiun televisi saat ini. Salah satu program acara talkshow di Trans7 yaitu Hitam Putih yang membahas informasi atau isu-isu terkini yang sedang hangat dibicarakan publik. Penelitian ini bertujuan untuk mengetahui adakah pengaruh gaya bicara presenter terhadap minat menonton masyarakat. Penelitian ini menggunakan konsep talkshow, presenter, minat dan teori social judgment. Pendekatan penelitian kuantitatif dengan jenis penelitian eksplanatif. Pada penelitian ini pengambilan sampel menggunakan teknik nonprobablity sampling dengan menggunakan conveniance sampling, yaitu berdasrkan kemudahan bagi peneliti dengan responden warga RT 11 RW 010 Kelurahan Pejaten Timur Pasar Minggu Jakarta Selatan dengan sampel sebanyak seratus responden. Hasil penelitian ini adalah nilai KMO Gaya Bicara Presenter 0,826 program Hitam Putih dan Minat menonton masyarakat 0,761 (valid). Uji validitas menggunakan KMO dengan nilai diatas 0.5, uji reliabilitas menggunakan Cronbach Alpha dengan nilai 0.6, uji regresi yang terdiri dari korelasi sebesar 0,731. Model summary sebesar 0,535 yang artinya variabel gaya bicara presenter program Hitam Putih terhadap minat menonton memiliki hubungan cukup kuat, berdasarkan penelitian ini dapat diketahui bahwa Gaya Bicara Presenter program Hitam Putih (Variabel X) berpengaruh cukup signifikan terhadap Minat menonton masyarakat (Variabel Y). Talkshow, Presenter, Minat Menonton, Teori Social Judgment.
RANCANG BANGUN SISTEM INFORMASI ADMINISTRASI KEUANGAN SEKOLAH BERBASIS WEBSITE MENGGUNAKAN FRAMEWORK LARAVEL DI SMPI LUKMAN HAKIM PAKISAJI
Authors: Seta Bagus , Darajat Pangestuti Prima , Choirina Priska , Mubarok Farchan Aziz
Published: August 2022

Sistem administrasi keuangan di SMPI Lukman Hakim masih menggunakan cara manual, yaitu menggunakan catatan buku. Oleh karena itu untuk mempermudah pengelolaan administrasi transaksi pemasukan dan pengeluaran dari dana Bantuan Operasional Sekolah (BOS) dan pembayaran siswa serta laporan keuangan di SMPI Lukman Hakim Pakisaji, dibuat sistem informasi administrasi keuangan sekolah yang berbasis website. Metode untuk pengembangan sistem yang akan digunakan dalam penelitian ini adalah menggunakan waterfall. Sistem administrasi keuangan dibangun menggunakan Bahasa Pemrograman PHP dan Framework Laravel. Di mana hasil pengujian menggunakan black box testing dapat diambil kesimpulan bahwa sistem yang telah dibuat ini dapat berfungsi dan hasil presentase keberhasilan dari setiap menu adalah 100%. Keunggulan dari website sistem administrasi keuangan sekolah ini adalah menu untuk mengirim notifikasi whatsapp yang digunakan untuk mengirim pesan kepada orangtua siswa ketika sudah melakukan pembayaran
Peningkatan Kemampuan Pemerintah Desa Dalam Manajemen Pelayanan Publik Di Desa Gampingan Kecamatan Pagak Kabupaten Malang
Authors: Fajriantina Lova Evi , Rizqi Amaliyah Angguliyah
Published: August 2022

Era otonomi daerah memberikan dampak signifikan pada sektor pelayanan  publik. Pelayanan publik memegang peran utama dan perlu diperhatikan khususnya pada pemerintah daerah setempat dalam melaksanakan pemerintahannya. Begitu juga dalam pemerintahan desa, pemerintahan desa dapat terlaksana dengan baik, salah satunya dapat dilihat dari bagaimana pelayanan publik yang diberikan pemerintah desa kepada masyarakatnya. Perlunya pengelolaan pelayanan publik yang baik untuk menciptakan ketertiban dan keteraturan sehingga pelaksanaan pelayanan publik dapat berjalan efektif dan efisien. Pemerintah Desa Gampingan, Kecamatan Pagak Kabupaten Malang, mempunyai beberapa masalah yang menjadi faktor pengahambat dalam pelaksanaan pelayanan publik yaitu perangkat desa dan tenaga administrasi yang belum  memiliki pengetahuan dan ketrampilan tentang pengelolaan pelayanan publik, selain  itu lemahnya sistem pengawasan dan masyarakat yang kurang aktif. Kegiatan pengabdian kepada masyarakat ini menggunakan metode pendidikan masyarakat dengan 3 (tiga) tahapan yaitu: 1) Perencanaan 2) Pelaksanaan dan 3) Evaluasi. Hasil dari pelaksanaan pengabdian ini yaitu dengan adanya peningkatan kemampuan dalam manajemen pelayanan publik pada Pemerintah Desa Gampingan dapat memberikan solusi atas permasalahan-permasalahan yang menghambat pelaksanaan pelayanan publik, salah satunya dengan mengoptimalkan rapat  pemerintah desa.
Si Wira Berbagi: Sosialisasi Wirausaha Berbasis Digital di Pondok Pesantren Daar el Nayl, Bogor, Jawa Barat
Authors: Bahrudin  , Dwi Saputra Maskhur
Published: August 2022

Pendidikan keterampilan hidup (life skill) yang berkaitan dengan wirausaha digital sangat diperlukan pada zaman sekarang. Hal ini dikarenakan ketika pandemi covid-19 banyak terjadi Pemutusan Hubungan Kerja (PHK). Disisi lain perkembangan teknologi begitu pesat yang dimanfaatkan untuk menjalankan aktivitas kehidupan di masyarakat salah satunya aktivitas wirausaha berbasis digital. Lembaga pendidikan perlu mengadopsi wirausaha digital dalam kegiatan pembelajaran agar peserta didik memiliki keterampilan hidup sesuai tuntutan zaman. Pondok Pesantren Daar el Nayl merupakan salah satu lembaha pendidikan yang belum mengajarkan tentang keterampilan hidup khususnya wirausaha digital, peserta didik hanya diajarkan tentang agama dan pengetahuan umum saja. Tujuan dari kegiatan ini yaitu memberikan sosialisasi wirausaha digital agar peserta didik memiliki pemahaman, sikap, dan karakter tentang wirausaha digital. Metode pelaksanaan dilakukan dengan penyuluhan yaitu memberikan ceramah dan diskusi terkait wirausaha digital. Hasil dari kegiatan ini yaitu terlaksananya penyampaian materi wirausaha digital pada peserta didik. Selain itu peserta didik juga cukup baik dalam merespon materi yang diberikan. Melalui kegiatan ini diharapkan peserta didik memiliki ide untuk mengembangkan potensi yang ada di dalam pondok pesantren.
Edukasi Seks Pada Anak Usia Dini melalui Media Digital dengan Metode StoryTelling
Authors: Pratiwi Mutia Rahmi , Mukaromah  , Subhiyakto Egia Rosi
Published: August 2022

Perkembangan media digital dewasa ini cenderung meningkat dan semakin banyak ragamnya. Instansi maupun organisasi dimanapun menggunakan media digital sebagai sarana promosi, penjualan, maupun mengabarkan informasi penting. Pemanfaatan media digital juga biasanya familiar dengan media edukasi yang digunakan di beberapa instansi maupun organisasi. TK Do’a Ibu Semarang merupakan salah satu lembaga pendidikan anak usia dini. Pihak sekolah belum memaksimalkan media edukasi digital yang tersedia. Tujuan pengabdian ini adalah memberikan pemahaman dan mengenalkan pentingnya pendidikan seksual bagi anak usia dini, yang tentunya disesuaikan dengan pemahaman dan daya pikir anak. Metode yang digunakan adalah dengan storytelling. Penggunaan metode ini didukung pengungkapan ekspresi yang disampaikan dengan percakapan sederhana seperti layaknya bercerita. Dalam bagian ini, ditunjang dengan adanya stimulus pendukung gambar yang ditampilkan dalam LCD, dan lembaran kertas ekspresi yang dipegang oleh anak. Anak menunjukan sikap senang dan antusias dalam proses belajar dan bermain dalam peer-grup, terbukti dengan proses interaksi dan respon yang positif.
Pendampingan Siswa dalam Penerapan Protokol Kesehatan untuk Mencegah Penularan Covid 19 di MI Matho’liul Falah Banyuwangi
Authors: Kurniawati Indah , Christiana Indah
Published: August 2022

Coronavirus Disease 2019 (COVID-19) adalah penyakit yang disebabkan oleh virus Sars-CoV-2 yang dapat menginfeksi manusia dan ditemukan di Wuhan-china dengan kasus kematian yang besar pada akhir tahun 2019. Kelompok yang memiliki  resiko rentan terkena virus corona 19 salah satunya adalah pada anak. Sekolah menjadi salah satu yang beresiko sebagai tempat penyebaran virus corona 19. Tujuan kegiatan ini adalah untuk memberikan edukasi dengan melakukan pendampingan pada siswa dalam menerapkan prokes untuk cegah penyebaran covid 19 dan minimalisir terjadinya klaster baru di sekolah. Metode pelaksanaan yang dilakukan dalam kegiatan pengabdian masyarakat ialah edukasi tentang penyakit Covid19 dan protokol kesehatan dan memberikan pendampingan terkait penerapan protokol kesehatan pada siswa dalam mencegah Covid-19. Hasil yang didapat adalah informasi tentang kesehatan serta pengetahuan protokol kesehatan dan cara mencegah  penularan  covid 19 pada lingkungan sekolah dilihat dengan peningkatan pengetahuan siswa tentang protokol kesehatan dan mampu mempraktekkannya. Kesimpulan dari hasil kegiatan ini adanya pengetahuan siswa yang mengalami peningkatan  dalam pencegahan penyebaran covid 19 serta penerapan protokol kesehatan  pada siswa di sekolah.
A Comparative Analysis of Human Rights Protection in European Union and African Union Countries: An fsQCA Approach
Authors: ADEWUSI Emmanuel Oluwatosin , KOCADAL Özker
Published: August 2022

This study contributes to the human rights protection literature by using Fuzzy-set Qualitative Comparative Analysis (fsQCA) in the analysis of 76 cases composed of European Union and African Union countries. Results indicate that the ratification of treaties, establishment of human rights institutions, and high GDP per capita in the absence of rule of law, play crucial roles in the high rate of protection of human rights in Europe. In Africa, however, the low GDP per capita and absence of rule of law significantly weaken human rights protection. The analysis reveals that the establishment of human rights institutions is essential to protect human rights in Europe, while high GDP per capita and rule of law are paramount to improving human rights protection in Africa in relation to any institutional configuration, approach, or policy.
If you encyst: evidence of parasite escape and host-switching among three co-occurring crabs
Authors: Barnard RB , Moore CS , Keogh CL , Blakeslee AMH
Published: August 2022

Biological invasions influence species interactions around the globe, including host and parasite communities. We evaluated trematode parasite diversity and the potential for host-switching of parasites in 3 co-occurring crabs in the Northeast USA, including 1 native species (Cancer irroratus) and 2 non-natives (Carcinus maenas, Hemigrapsus sanguineus), of which the former represents a historical and the latter a contemporary invader. At 7 sites from Maine to Rhode Island, we surveyed crabs for trematode infection prevalence and abundance, and the influence of parasitism on host body condition. We also conducted DNA sequencing using the 18S rRNA barcoding marker to determine species composition, diversity, and gene flow of trematode lineages among the co-occurring hosts. While the native host, C. irroratus, and the historical invader, C. maenas, exhibited no statistical difference in trematode prevalence, we found that C. maenas had a greater abundance of metacercarial cysts than the other 2 hosts, and the contemporary invader, H. sanguineus, was rarely infected. Crab condition did not vary with infection abundance, although infected females of all species had higher reproductive investment than other groups. Genetic analyses revealed that the microphallid trematodes consisted of 3 main clades, representing over 50 haplotypes, with evidence of host-switching by native parasites utilizing the non-native hosts. Given the importance of crustaceans to parasite life cycles, the introduction of novel hosts to these systems alters both free-living and host-parasite community interactions and could ultimately affect community structure and function. Future studies should continue to investigate host-parasite diversity and demographics following invasions to better understand impacts on native marine communities.
Effects of acute footshock stress on antioxidant enzyme activities in the adolescent rat brain.
Authors: Uysal N , Acikgoz O , Gönenç S , Kayatekin BM , Kiray M , Sönmez A , Şemin İ
Published: August 2022

In a previous study we demonstrated that acute footshock stress increased glutathione peroxidase activity in the prefrontal cortex and striatum of adult male rats. Adolescents may respond differently to stress as life stressors may be greater than at other ages. The present study examined the effects of the acute footshock stress on superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities and thiobarbituric acid reactive substances (TBARS) levels in adolescent male and female rat brains. We demonstrated that acute footshock stress increased SOD activity in the prefrontal cortex, and increased GPx activity in the hippocampus in female rats. In males, acute footshock stress increased GPx activity in the prefrontal cortex and hippocampus. Footshock stress did not change TBARS levels. These results indicate a strong role of gender in the response of adolescent subjects to various aspects of stress.
Hemodynamic response to laparoscopic cholecystectomy – impacts of increased afterload and ischemic dysfunction of the left ventricle.
Authors: Danzig V , Krška Z , Demeš R , Danzigová Z , Linhart A , Kittnar O
Published: August 2022

The authors describe the results of intra-operative hemodynamic monitoring during laparoscopic cholecystectomy in patients with ischemic left ventricular dysfunction and with significant aortic stenosis. The results in the groups composed of 13 and 12 patients were compared with the findings in 10 young, non-obese, non-smokers without significant cardiovascular history and with normal findings during resting transthoracic echocardiography. Monitoring itself was conducted using transesophageal echocardiography 1) after the induction of anesthesia, 2) after the induction of capnoperitoneum, and 3) after setting the operative anti-Trendelenburg position. The measurements were performed at least in triplicate and the results were processed using ANOVA test. Significant differences were identified in the time course patterns of heart rate, mean arterial pressure, dual product (pressure-rate-product), and cardiac output. In terms of pathophysiology, we believe that the most important achievement was the identification of different time course patterns of individual parameters in the respective groups. The results in the group of patients with aortic stenosis were based particularly on the different time course of the mean arterial pressure, while the results in patients with ischemic disease were more dependent on the time course of the heart rate. Very ineteresting is a drop of peripheral vascular resistance after positioning of these patients which could be explained only partially by a beta-blocking or ACEI medication. In clinical terms, the most important finding was probably that no complications occurred in the entire group of 35 patients, of which 25 suffered from severe organic cardiopathies.
Inconsistent effect of nitric oxide on lipolysis in isolated rat adipocytes.
Authors: Canová N , Lincová D , Farghali H
Published: August 2022

Though two isoforms of nitric oxide synthase, iNOS and eNOS, were reported in adipocytes, the role of NO in adipose tissue is still ambiguous. The aims of the present study were 1) to follow the effect of bacterial lipopolysaccharide (LPS), on 24 h-lipolysis in rat epididymal adipocyte culture in relation to iNOS stimulation; 2) to compare LPS-induced NO effects with exogenously NO, delivered as S-nitroso-N-acetylpenicillamine (SNAP), and 3) to examine the possible role of NO signaling agonist in lipolysis mediated by the -adrenoreceptor agonist. Lipolysis was measured by glycerol and free fatty acid (FFA) production. The medium nitrite levels were used for the indirect estimation of NOS expression. Adipocyte mitochondrial function was assessed by the MTT test. LPS produced a concentration-dependent increase of NO with a decrease of viability at the highest dose. However, LPS did not affect lipolysis. SNAP did not exhibit significant changes in glycerol, FFA or MTT. BRL-37344 and db-cAMP significantly increased nitrite, glycerol and FFA levels. There was a positive correlation between glycerol release and nitrite production. Moreover, BRL-37344 significantly reduced mitochondrial functions. The pretreatment with bupranolol, -antagonist, restored all parameters affected by BRL-37344. These results support a concept that NO fulfils multifaceted role of stimulating lipolysis under physiological conditions (-agonistic effect) and modulating the same processes during inflammatory (LPS) processes.
Comparison of different methods of time shift measurement in EEG.
Authors: Jiruška P , Prokš J , Drbal O , Sovka P , Marusič P , Mareš P
Published: August 2022

Digital signal processing techniques are often used for measurement of small time shifts between EEG signals. In our work we tested properties of linear cross-correlation and phase/coherence method. The last mentioned method was used in two versions. The first version used fast Fourier transform (FFT) algorithm and the second was based on autoregressive modeling with fixed or adaptive model order. Methods were compared on several testing signals mimicking real EEG signals. The accuracy index for each method was computed. Results showed that for long signal segments all methods bring comparably good results. Accuracy of FFT phase/coherence method significantly decreased when very short segments were used and also decreased with an increasing level of the additive noise. The best results were obtained with autoregressive version of phase/coherence. This method is more reliable and may be used with high accuracy even in very short signals segments and it is also resistant to additive noise.
Tracing coal transitions: A report on opencast coal mining in Colombian and Scottish film and video archives
Authors: Velez-Serna Maria A.
Published: August 2022

This report offers a descriptive account of a first stage of archival work for the project ‘Representing energy transitions: Colombian and Scottish coalmining on film’, funded by the Royal Society of Edinburgh. The project aims to contribute to the historical understanding of energy transitions by exploring the use of the moving image in the movement to phase in large-scale coal extraction in Colombia, and to phase down pit mining in Scotland. This report explains the catalogue search method and its results for different relevant keywords at four moving image archives in Colombia and the UK (Fundación Patrimonio Fílmico Colombiano, RTVC Señal Memoria, National Library of Scotland - Moving Image Archive, and British Film Institute - National Film Archive). It also offers an overview of corporate publications consulted at other archives. The report aims to make transparent the archive research underpinning further critical discussion of the material, which is in progress.
The first report of chickpea (Cicer arietinum L.) tolerance to Paraquat in Australia
Authors: Mahajan Gulshan , Chauhan Bhagirath S.
Published: August 2022

Chickpea growers in Australia have no post-emergent (POST) herbicides labeled for broadleaf weed control and they rely on pre-emergent herbicides for control of broadleaf weeds. The objective of this study was to evaluate chickpea tolerance to POST application of paraquat (0, 90, 180, 360, and 540 g ai ha-1) in a randomized complete block design. Paraquat (180 g ai ha-1) applied POST (up to 10 days after crop emergence) did not injure chickpeas and reduce plant height, and biomass when compared with nontreated control. When the crop just emerged, even the highest dose of paraquat (540 g ai ha-1) did not cause any injury or reduce chickpea biomass compared with nontreated control. Moderate toxicity to chickpea at paraquat 360 or 540 g ai ha-1 was observed when applied 20 days after crop emergence. This study suggests that paraquat POST has the potential to provide broad-spectrum weed control, including broadleaf weeds at an early stage of chickpea. However, the potential for crop injury to paraquat at higher doses, especially when applied at a late stage of the crop warrants further evaluation under field conditions. The study also suggests that tank mix applications of paraquat with residual herbicides may be useful for season-long weed control in chickpea and result in improved yield. The current study warrants further evaluation of the tank-mix application of paraquat with pre-emergent herbicides for season-long weed control under field conditions.
Basement Membrane of Tissue Engineered Extracellular Matrix Scaffolds Modulates Rapid Human Endothelial Cell Recellularization and Promote Quiescent Behavior After Monolayer Formation
Authors: Lopera Higuita Manuela , Shortreed Nicholas A. , Dasari Surendra , Griffiths Leigh G.
Published: August 2022

Off-the-shelf small diameter vascular grafts are an attractive alternative to eliminate the shortcomings of autologous tissues for vascular grafting. Bovine saphenous vein (SV) extracellular matrix (ECM) scaffolds are potentially ideal small diameter vascular grafts, due to their inherent architecture and signaling molecules capable of driving repopulating cell behavior and regeneration. However, harnessing this potential is predicated on the ability of the scaffold generation technique to maintain the delicate structure, composition, and associated functions of native vascular ECM. Previous de-cellularization methods have been uniformly demonstrated to disrupt the delicate basement membrane components of native vascular ECM. The antigen removal (AR) tissue processing method utilizes the protein chemistry principle of differential solubility to achieve a step-wise removal of antigens with similar physiochemical properties. Briefly, the cellular components of SV are permeabilized and the actomyosin crossbridges are relaxed, followed by lipophilic antigen removal, sarcomeric disassembly, hydrophilic antigen removal, nuclease digestion, and washout. Here, we demonstrate that bovine SV ECM scaffolds generated using the novel AR approach results in the retention of native basement membrane protein structure, composition (e.g., Collagen IV and laminin), and associated cell modulatory function. Presence of basement membrane proteins in AR vascular ECM scaffolds increases the rate of endothelial cell monolayer formation by enhancing cell migration and proliferation. Following monolayer formation, basement membrane proteins promote appropriate formation of adherence junction and apicobasal polarization, increasing the secretion of nitric oxide, and driving repopulating endothelial cells toward a quiescent phenotype. We conclude that the presence of an intact native vascular basement membrane in the AR SV ECM scaffolds modulates human endothelial cell quiescent monolayer formation which is essential for vessel homeostasis.
The role of tryptophan in Chlamydia trachomatis persistence
Authors: Wang Li , Hou YingLan , Yuan HongXia , Chen Hongliang
Published: August 2022

Chlamydia trachomatis (C. trachomatis) is the most common etiological agent of bacterial sexually transmitted infections (STIs) and a worldwide public health issue. The natural course with C. trachomatis infection varies widely between individuals. Some infections clear spontaneously, others can last for several months or some individuals can become reinfected, leading to severe pathological damage. Importantly, the underlying mechanisms of C. trachomatis infection are not fully understood. C. trachomatis has the ability to adapt to immune response and persist within host epithelial cells. Indoleamine-2,3-dioxygenase (IDO) induced by interferon-gamma (IFN-γ) degrades the intracellular tryptophan pool, to which C. trachomatis can respond by converting to a non-replicating but viable state. C. trachomatis expresses and encodes for the tryptophan synthase (TS) genes (trpA and trpB) and tryptophan repressor gene (trpR). Multiple genes interact to regulate tryptophan synthesis from exogenous indole, and persistent C. trachomatis can recover its infectivity by converting indole into tryptophan. In this review, we discuss the characteristics of chlamydial infections, biosynthesis and regulation of tryptophan, the relationship between tryptophan and C. trachomatis, and finally, the links between the tryptophan/IFN-γ axis and C. trachomatis persistence.
Genome characterization of a uropathogenic Pseudomonas aeruginosa isolate PA_HN002 with cyclic di-GMP-dependent hyper-biofilm production
Authors: Lin Siying , Chen Shuzhen , Li Li , Cao Huiluo , Li Ting , Hu Ming , Liao Lisheng , Zhang Lian-Hui , Xu Zeling
Published: August 2022

Pseudomonas aeruginosa can cause various types of infections and is one of the most ubiquitous antibiotic-resistant pathogens found in healthcare settings. It is capable of adapting to adverse conditions by transforming its motile lifestyle to a sessile biofilm lifestyle, which induces a steady state of chronic infection. However, mechanisms triggering the lifestyle transition of P. aeruginosa strains with clinical significance are not very clear. In this study, we reported a recently isolated uropathogenic hyper-biofilm producer PA_HN002 and characterized its genome to explore genetic factors that may promote its transition into the biofilm lifestyle. We first showed that high intracellular c-di-GMP content in PA_HN002 gave rise to its attenuated motilities and extraordinary strong biofilm. Reducing the intracellular c-di-GMP content by overexpressing phosphodiesterases (PDEs) such as BifA or W909_14950 converted the biofilm and motility phenotypes. Whole genome sequencing and comprehensive analysis of all the c-di-GMP metabolizing enzymes led to the identification of multiple mutations within PDEs. Gene expression assays further indicated that the shifted expression profile of c-di-GMP metabolizing enzymes in PA_HN002 might mainly contribute to its elevated production of intracellular c-di-GMP and enhanced biofilm formation. Moreover, mobile genetic elements which might interfere the endogenous regulatory network of c-di-GMP metabolism in PA_HN002 were analyzed. This study showed a reprogrammed expression profile of c-di-GMP metabolizing enzymes which may promote the pathoadaption of clinical P. aeruginosa into biofilm producers.
A thousand metagenome-assembled genomes of Akkermansia reveal phylogroups and geographical and functional variations in the human gut
Authors: Lv Qing-Bo , Li Shenghui , Zhang Yue , Guo Ruochun , Wang Yan-Chun , Peng Yongzheng , Zhang Xiao-Xuan
Published: August 2022

Akkermansia muciniphila has long been considered to be the only Akkermansia species in the human gut and has been extensively studied. The present study revealed the genomic architecture of Akkermansia in the human gut by analyzing 1,126 near-complete metagenome-assembled genomes, 84 publicly available genomes, and 1 newly sequenced Akkermansia glycaniphila strain from the human gut. We found that 1) the genomes of Akkermansia were clustered into four phylogroups with distinct interspecies similarity and different genomic characteristics and 2) A. glycaniphila GP37, a strain of Akkermansia, was isolated from the human gut, whereas previously, it had only been found in python. Amuc III was present in the Chinese population, and Amuc IV was mainly distributed in Western populations. A large number of gene functions, pathways, and carbohydrate-active enzymes were specifically associated with phylogroups. Our findings based on over a thousand genomes strengthened our previous knowledge and provided new insights into the population structure and ecology of Akkermansia in the human gut.
habCluster: identifying the geographical boundary among intraspecific units using community detection algorithms in R
Authors: Zhang Chengcheng , Li Juan , Yang Biao , Dai Qiang
Published: August 2022

Conservation management for a species generally rests on intraspecific units, while identification of their geographic boundaries is necessary for the implementation. Intraspecific units can be discriminated using population genetic methods, yet an analytical approach is still lacking for detecting their geographic boundaries. Here, based on landscape connectivity, we present a raster-based geographical boundary delineation method, habCluster, using community detection algorithms. Community detection is a technique in graph theory used to identify clusters of highly connected nodes within a network. We assume that the habitat raster cells with better connections tend to form a continuous habitat patch than the others, thus making the range of an intraspecific unit. The method was tested on the gray wolf (Canis lupus) habitat in Europe and the giant panda (Ailuropoda melanoleuca) habitat in China. The habitat suitability index (HSI) maps for gray wolves and giant pandas were evaluated using species distribution models. Each cell in the HSI raster is treated as a node and directly connected with its eight neighbor cells. The edge weight between nodes is the reciprocal of the relative distance between the centers of the nodes weighted by the average of their HSI values. We implement habCluster using the R programming language with the inline C++ code to speed up the computing. We found that the boundaries of the clusters delineated using habCluster could serve as a good indicator of habitat patches. In the giant panda case, the clusters match generally well with nature reserves. habCluster can provide a spatial analysis basis for conservation management plans such as monitoring, translocation and reintroduction, and population structure research.
Multi-organ FGF21-FGFR1 signaling in metabolic health and disease
Authors: Kaur Namrita , Gare Sanskruti Ravindra , Shen Jiahan , Raja Rida , Fonseka Oveena , Liu Wei
Published: August 2022

Metabolic syndrome is a chronic systemic disease that is particularly manifested by obesity, diabetes, and hypertension, affecting multiple organs. The increasing prevalence of metabolic syndrome poses a threat to public health due to its complications, such as liver dysfunction and cardiovascular disease. Impaired adipose tissue plasticity is another factor contributing to metabolic syndrome. Emerging evidence demonstrates that fibroblast growth factors (FGFs) are critical players in organ crosstalk via binding to specific FGF receptors (FGFRs) and their co-receptors. FGFRs activation modulates intracellular responses in various cell types under metabolic stress. FGF21, in particular is considered as the key regulator for mediating systemic metabolic effects by binding to receptors FGFR1, FGFR3, and FGFR4. The complex of FGFR1 and beta Klotho (β-KL) facilitates endocrine and paracrine communication networks that physiologically regulate global metabolism. This review will discuss FGF21-mediated FGFR1/β-KL signaling pathways in the liver, adipose, and cardiovascular systems, as well as how this signaling is involved in the interplay of these organs during the metabolic syndrome. Furthermore, the clinical implications and therapeutic strategies for preventing metabolic syndrome and its complications by targeting FGFR1/β-KL are also discussed.
The role of osteocalcin in regulation of glycolipid metabolism and muscle function in children with osteogenesis imperfecta
Authors: Zheng Wen-bin , Hu Jing , Zhao Di-Chen , Zhou Bing-Na , Wang Ou , Jiang Yan , Xia Wei-Bo , Xing Xiao-ping , Li Mei
Published: August 2022

Objective

Osteoblasts are discovered to secrete hormones with endocrine effects on metabolism, and osteocalcin (OC) is the most abundant non-collagenous protein in bone. We investigate the relationship between serum OC levels and glycolipid metabolism and muscle function in children with osteogenesis imperfecta (OI).

Methods

A total of 225 children with OI and 80 healthy controls matched in age and gender were included in this single center study. Serum levels of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDL-C, HDL-C) were measured by automated analyzers. Serum levels of fasting insulin (FINS) were measured using an automated electrochemiluminescence system. Serum levels of OC and undercarboxylated osteocalcin (ucOC) were measured by enzyme-linked immunosorbent assay. Grip strength and timed-up-and-go (TUG) test were measured. Bone mineral density (BMD) and body composition were measured using dual-energy X-ray absorptiometry.

Results

OI patients had significantly higher body mass index (BMI), FBG, and HOMA-IR, but lower HDL-C levels, lower grip strength and longer TUG than control group (all P<0.05). Serum OC, ucOC levels, and ucOC/OC in OI type III patients were significantly lower than those in OI patients with type I and IV. Serum levels of OC, ucOC, and ucOC/OC were negatively correlated to BMI, FBG, insulin levels, and HOMA-IR (all P<0.05). The ratio of ucOC/OC was positively correlated to grip strength (r=0.512, P=0.036), lean mass percentage (%LM) of the total body and limbs, and negatively correlated to fat mass percentage (%FM) of the total body, %FM and fat mass index (FMI) of the trunk (all P<0.05).

Conclusions

Obesity, glucolipid metabolic abnormalities, and reduced grip strength were common in children with OI. Circulating osteocalcin and ucOC may play an important role in the regulation of glucose metabolism, as well as the muscle function of children with OI.
Spatiotemporal patterns of gross ecosystem product across China's cropland ecosystems over the past two decades
Authors: Zhang Jiaying , Song Yang , Wang Jing
Published: August 2022

As the largest artificial ecosystem on Earth, croplands not only secure the basic living materials for people but also provide ecological service values for human society. For croplands, ecosystem services have proven to be of great value and are closely linked to human activities and climate change. However, spatiotemporal patterns of cropland ecosystem services and their drivers still need to be further assessed quantitatively. In this study, we provided a comprehensive evaluation of ecosystem services across China's cropland ecosystems over the past two decades using gross ecosystem product (GEP) as a single metric of the monetary evaluation of final ecosystem services. The values of material services, regulating services, and cultural services were calculated to summarize the GEP value of cropland ecosystems in China. Our results showed that the multiyear mean value of GEP was 4.35 × 107 million CNY. The value of regulating services reached 3.86 × 107 million CNY, followed by material services of 4.76 × 106 million CNY and cultural services of 1.16 × 105 million CNY. GEP value was different among provinces, leading to a heterogeneous spatial pattern associated with population and cultivated area. Moreover, we analyzed the trends in the GEP value at the provincial and national scales. The results showed that the GEP value of China's cropland ecosystems has increased over the period. The values of the material, regulating, and cultural services have increased at a rate of (0.35 ± 0.01) × 106 million CNY a−1, (1.12 ± 0.10) × 106 million CNY a−1, and (0.002 ± 0.0002) × 106 million CNY a−1, respectively (P < 0.05). The majority of provinces had an increasing trend in GEP, yet some developed provinces, e.g., Beijing and Shanghai, showed a decreasing trend. Furthermore, we evaluated the impacts of social-economic and natural factors on changes in GEP. We found that rising prices for agricultural products and services boosted an increase in GEP. Meanwhile, the spatiotemporal patterns of GEP were also associated with the adjustments of planting area in each province. Overall, our findings highlight the importance of assessing spatiotemporal patterns of cropland ecosystem services for decision-makers.
Molecular mapping of QTLs for grain dimension traits in Basmati rice
Authors: Malik Ankit , Kumar Aruna , Ellur Ranjith Kumar , Krishnan S Gopala , Dixit Deepshikha , Bollinedi Haritha , Vinod KK , Nagarajan M , Bhowmick PK , Singh NK , Singh AK
Published: August 2022

Basmati rice is known for its extra-long slender grains, exceptional kernel dimensions after cooking, high volume expansion, and strong aroma. Developing high yielding Basmati rice varieties with good cooking quality is a gigantic task. Therefore, identifying the genomic regions governing the grain and cooked kernel dimension traits is of utmost importance for its use in marker-assisted breeding. Although several QTLs governing grain dimension traits have been reported, limited attempts have been made to map QTLs for grain and cooked kernel dimension traits of Basmati rice. In the current study, a population of recombinant inbred lines (RIL) was generated from a cross of Sonasal and Pusa Basmati 1121 (PB1121). In the RIL population, there was a significant positive correlation among the length (RRL: rough rice length, MRL: milled rice length, CKL: cooked kernel length) and breadth (RRB: rough rice breadth, MRB: milled rice breadth and CKB: cooked kernel breadth) of the related traits, while there was significant negative correlation between them. QTL mapping has led to the identification of four major genomic regions governing MRL and CKL. Two QTLs co-localize with the earlier reported major gene GS3 and a QTL qGRL7.1, while the remaining two QTLs viz., qCKL3.2 (qMRL3.2) and qCKL4.1 (qMRL4.1) were novel. The QTL qCKL3.2 has been bracketed to a genomic region of 0.78 Mb between the markers RM15247 and RM15281. Annotation of this region identified 18 gene models, of which the genes predicted to encode pentatricopeptides and brassinosteroid insensitive 1-associated receptor kinase 1 precursor may be the putative candidate genes. Furthermore, we identified a novel QTL qKER2.1 governing kernel elongation ratio (KER) in Basmati rice.
Utomilumab in Patients With Immune Checkpoint Inhibitor-Refractory Melanoma and Non-Small-Cell Lung Cancer
Authors: Hong David S. , Gopal Ajay K. , Shoushtari Alexander N. , Patel Sandip P. , He Aiwu R. , Doi Toshihiko , Ramalingam Suresh S. , Patnaik Amita , Sandhu Shahneen , Chen Ying , Davis Craig B. , Fisher Timothy S. , Huang Bo , Fly Kolette D. , Ribas Antoni
Published: August 2022

Section Head

Clinical/translational cancer immunotherapy

Background

The goal of this study was to estimate the objective response rate for utomilumab in adults with immune checkpoint inhibitor (ICI)-refractory melanoma and non–small-cell lung cancer (NSCLC).

Methods

Utomilumab was dosed intravenously every 4 weeks (Q4W) and adverse events (AEs) monitored. Tumor responses by RECIST1.1 were assessed by baseline and on-treatment scans. Tumor biopsies were collected for detection of programmed cell death ligand 1, CD8, 4-1BB, perforin, and granzyme B, and gene expression analyzed by next-generation sequencing. CD8+ T cells from healthy donors were stimulated with anti-CD3 ± utomilumab and compared with control.

Results

Patients with melanoma (n=43) and NSCLC (n=20) received utomilumab 0.24 mg/kg (n=36), 1.2 mg/kg (n=26), or 10 mg/kg (n=1). Treatment-emergent AEs (TEAEs) occurred in 55 (87.3%) patients and serious TEAEs in 18 (28.6%). Five (7.9%) patients discontinued owing to TEAEs. Thirty-two (50.8%) patients experienced treatment-related AEs, mostly grade 1–2. Objective response rate: 2.3% in patients with melanoma; no confirmed responses for patients with NSCLC. Ten patients each with melanoma (23.3%) or NSCLC (50%) had stable disease; respective median (95% confidence interval, CI) progression-free survival was 1.8 (1.7–1.9) and 3.6 (1.6–6.5) months. Utomilumab exposure increased with dose. The incidences of antidrug and neutralizing antibodies were 46.3% and 19.4%, respectively. Efficacy was associated with immune-active tumor microenvironments, and pharmacodynamic activity appeared to be blunted at higher doses.

Conclusions

Utomilumab was well tolerated, but antitumor activity was low in patients who previously progressed on ICIs. The potential of 4-1BB agonists requires additional study to optimize efficacy while maintaining the tolerable safety profile.
Level of interleukin-35 in patients with idiopathic membranous nephropathy and its predictive value for remission time
Authors: Zhang Na , Dai Haoran , Dong Xuan , Liu Wenbin , Jiang Hanxue , Zhao Qihan , Gao Yu , Feng Zhendong , Dong Zhaocheng , Hu Yuehong , Huang Guangrui , Rui Hongliang , Liu Baoli
Published: August 2022

Objective

As a member of interleukin-12 family, interleukin-35 (IL-35) plays an important regulatory role in immune response. The relationship between IL-35 and idiopathic membranous nephropathy (IMN) is still unclear, and the purpose of this study is to clarify the relationship between IL-35 and disease activity and remission of IMN.

Methods

This study was a single-center, retrospective study in which all patients were diagnosed with IMN by renal biopsy or aPLA2R titer and treated with Mahuang Fuzi and Shenzhuo Decoction (MFSD). A follow-up was conducted with the endpoint of clinical complete or partial remission (CR+PR). Levels of serum IL-35 were measured and its relationship with IMN remission were analyzed. The regulatory T cell (Treg) and inducible IL-35 producing Tregs (iTR35) in peripheral blood of IMN patients were detected by flow cytometry.

Results

A total of 76 IMN patients (age 51.95 ± 13.29) were followed-up for 18 (12, 24) months. The level of serum IL-35 in all patients increased after treatment, but the degree of increase in remission group was significantly higher than that in no remission (NR) group (117.6% vs 83.7%, P<0.01). The baseline IL-35 level in remission group was higher than that in NR group (174.87 vs.151.87 pg/ml, P=0.016). Cox regression analysis showed that baseline IL-35 level was a independent risk factor for IMN remission (HR 1.081, 95%CI 1.048-1.116, P<0.001). Patients with baseline IL-35 lower than the lower quartile (≤145.49 pg/ml) had an average remission time twice as long as those with baseline IL-35 higher than the upper quartile (> 203.05 pg/ml) (12mon vs. 24mon, P<0.01). The baseline IL-35 can predict the remission time of IMN patients with either aPLA2R positive (AUC=0.673) or negative (AUC=0.745). Analysis of 18 patients with IMN showed that IL-35 level had a higher correlation with iTR35, but not Treg (r=0.613, P<0.05).

Conclusions

The level of IL-35 in patients with IMN showed an increasing trend with the progress of treatment, and the baseline IL-35 could predict the remission time of IMN patients, including those patients with negative aPLA2R. The level of IL-35 is related to the number of iTR35 cells.
Robust and durable response to first-line treatment of pembrolizumab combined with chemotherapy in two patients with metastatic thymic squamous cell carcinoma: Case report
Authors: Chen Cui , Sun Peng , Long Jianting
Published: August 2022

Thymic carcinoma is a rare and aggressive disease with poor outcome. There is no established treatment regimen for advanced thymic carcinoma. While the efficacy of pembrolizumab was proved to be promising, as a single agent, in patients with refractory/recurrent thymic carcinoma that progressed after chemotherapy, the efficacy and safety of combination of pembrolizumab and chemotherapy as front-line treatment in metastatic thymic carcinoma have not been explored yet. Herein, we report the first two cases of metastatic thymic squamous cell carcinoma receiving the combined approaches of pembrolizumab and chemotherapy as first-line treatment. Of the two patients, one had a complete radiological response of mediastinal masses with sustained remission over 3 years, and the other one with widespread disease had a good partial response over 20 months and achieved no evidence of disease radiologically after undergoing percutaneous radiofrequency ablation for residual liver metastases. Next-generation sequencing (NGS) showed low tumor mutation burden and MSS in both patients. Immunohistochemistry analysis of the tumor showed high PD-L1 expression in patient 1 and low PD-L1 expression in patient 2. Pembrolizumab combined with chemotherapy may be an attractive strategy for the first-line treatment of metastatic thymic carcinoma and thus warrants further evaluation.
Exploring the function of stromal cells in cholangiocarcinoma by three-dimensional bioprinting immune microenvironment model
Authors: Li Changcan , Jin Bao , Sun Hang , Wang Yunchao , Zhao Haitao , Sang Xinting , Yang Huayu , Mao Yilei
Published: August 2022

The tumor immune microenvironment significantly affects tumor progression, metastasis, and clinical therapy. Its basic cell components include tumor-associated endothelial cells, fibroblasts, and macrophages, all of which constitute the tumor stroma and microvascular network. However, the functions of tumor stromal cells have not yet been fully elucidated. The three-dimensional (3D) model created by 3D bioprinting is an efficient way to illustrate cellular interactions in vitro. However, 3D bioprinted model has not been used to explore the effects of stromal cells on cholangiocarcinoma cells. In this study, we fabricated 3D bioprinted models with tumor cells and stromal cells. Compared with cells cultured in two-dimensional (2D) environment, cells in 3D bioprinted models exhibited better proliferation, higher expression of tumor-related genes, and drug resistance. The existence of stromal cells promoted tumor cell activity in 3D models. Our study shows that 3D bioprinting of an immune microenvironment is an effective way to study the effects of stromal cells on cholangiocarcinoma cells.