bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavior Analysis of Students in Utilizing Faculty of Agriculture Library, Gadjah Mada University
Authors: Hidayah Laili , Junandi Sri , Wahyuningsih Yuli Hesti
Published: February 2021

Problem Statement: The behavior of students in utilizing the library is very diverse, so it needs to be examined further. Purpose: This study examines the extent of student behavior in using the library and what factors influence student behavior in utilizing the Library of the Faculty of Agriculture Universitas Gadjah Mada. Method: This research is descriptive qualitative and data collection uses observation, in-depth interviews and documentation. Result: The results of the study indicate that the behavior of students to the library is diverse in terms of attitudes, encouragement and expectations in using the library. The diversity of behavior is still in the library's goal as a source of learning, entertainment and research. Conclusion: The factors that influence the attitude of behavior using the Library are the environment, facilities, type of service, room, wifi access and staff. Students are of the opinion that these factors that influence it utilize the Library of the Faculty of Agriculture Universitas Gadjah Mada.

Keywords: behavior, utilization,  library,  Faculty of Agriculture UGM

 

ABSTRAK

Permasalahan: Perilaku mahasiswa dalam memanfaatkan perpustakaan sangat beragam, terlebih dengan adanya perkembangan teknologi yang sangat pesat mengubah juga perilaku belajarnya di perpustakaan. Tujuan: Penelitian ini menelaah sejauhmana perilaku mahasiswa dalam memanfaatkan perpustakaan dan faktor-faktor apa saja yang mempengaruhi perilaku mahasiswa dalam memanfaatkan Perpustakaan Fakultas Pertanian Universitas Gadjah Mada. Metode: Penelitian ini bersifat deskriptif kualitatif dan pengumpulan datanya menggunakan observasi, wawancara mendalam dan dokumentasi. Hasil: Hasil penelitian yang diperoleh menunjukkan bahwa perilaku mahasiswa ke Perpustakaan beraneka ragam dilihat dari sikap, dorongan dan harapan dalam memanfaatkan perpustakaan. Keberagaman perilaku tersebut masih pada tujuan perpustakaan sebagai sumber belajar, hiburan dan penelitian. Kesimpulan: Faktor-faktor yang mempengaruhi sikap perilaku mahasiswa dalam memanfaatkan Perpustakaan adalah lingkungan, sarana prasarana, jenis layanan, ruangan, akses wifi dan stafnya. Mahasiswa berpendapat bahwa faktor tersebut yang mempengaruhinya memanfaatkan Perpustakaan Fakultas Pertanian Universitas Gadjah Mada.

Kata kunci: perilaku, pemanfaatan, perpustakaan, Fakultas Pertanian UGM
Management of Librarian to Supporting Lecturer's Performance in Higher Education
Authors: Rahmadanita Annisa , Hasmiati Hasmiati
Published: February 2021

Problem Statement: The author focuses on the problem of limited human resources of IPDN libraries. Purpose: This study is focused on knowing the description of IPDN library human resource management in supporting the performance of lecturers in the IPDN environment. Method: The author collects data through interviews, observation, documentation. Result: The results showed that from the aspect of planning and organizing, there was an inadequate number of human resources, as well as the quality of human resources that needed to be improved in the IPDN Library. Conclusion: Library human resource management in supporting the performance of lecturers at IPDN has been carried out quite well, but IPDN Libraries need to make improvements and improvements from the aspects of planning and organizing, namely by adding personnel and developing human resources.

Keywords: Management; Librarian; Human Resource; Lecturer's Performance; Higher Education

 

ABSTRAK

Permasalahan: Penulis berfokus pada permasalahan terbatasnya sumber daya manusia perpustakaan IPDN.  Tujuan: Studi ini difokuskan untuk untuk mengetahui gambaran manajemen sumber daya manusia perpustakaan IPDN dalam mendukung kinerja dosen di lingkungan IPDN. Metode:  Penulis mengumpulkan data melalui wawancara, observasi, dokumentasi. Hasil: Hasil penelitian menunjukkan bahwa dari aspek perencanaan dan pengorganisasian, terdapat jumlah sumber daya manusia yang kurang memadai, serta kualitas sumber daya manusia yang perlu ditingkatkan di Perpustakaan IPDN. Kesimpulan: Manajemen sumber daya manusia perpustakaan dalam mendukung kinerja dosen di IPDN sudah terlaksana cukup baik, namun Perpustakaan IPDN perlu melakukan perbaikan dan peningkatan dari aspek perencanaan dan pengorganisasian, yaitu dengan menambah personil dan melakukan pengembangan sumber daya manusia. 

Kata kunci: Manajemen; Pustakawan; Sumber daya manusia; Kinerja Dosen; Perguruan Tinggi
Analisis Rasio Tingkat Kesehatan Bank Menggunakan Metode CAMEL Pada PT Bank BCA Syariah Tbk Jakarta Timur Tahun 2013 - 2017
Authors: Patmin Su
Published: February 2021

The purpose of this study was to determine the development of bank health at PT Bank BCA Syariah Tbk and to measure the level of health of PT Bank BCA Syariah Tbk in 2013-2017 using the CAMEL ratio which includes aspects of capital, productive assets, management, profitability and liquidity. This research is quantitative descriptive. The population in this study includes all financial statements of PT Bank BCA Syariah for the period 2013 to 2017, while the sample in this study is the company's financial statements in the form of a balance sheet and income statement of PT. Bank BCA Syariah Tbk. period 2013 to 2017. Analysis of the data used in this study is to use the CAMEL method which consists of five aspects, namely capital aspects using CAR (Capital Adequacy Ratio), aspects of earning asset quality using the ratio of KAP (Earning Assets Quality) and PPAP (Allowance for Earning Assets), management aspects using the ratio of NPM (Net Profit Margin), profitability aspects using the ratio of ROA (Return On Assets) and BOPO (Operating Expenses to Operating Income), and the liquidity aspect using the NCM-CA (Net Call Money ratio) to Current Assets) and LDR (Loan to Deposit Ratio). Based on the results of research conducted at PT Bank BCA Syariah CAMEL in 2013 97.04 was healthy, in 2014 96.71 was healthy, in 2015 95.52 was healthy, in 2016 97.01 was healthy, in 2017 98.00 is healthy.

Abstrak

Tujuan penelitian ini untuk mengetahui perkembangan kesehatan bank pada PT Bank BCA Syariah Tbk dan untuk mengukur tingkat kesehatan PT Bank BCA Syariah Tbk pada tahun 2013-2017 dengan menggunakan rasio CAMEL yang meliputi aspek permodalan, aktiva produktif, manajemen, rentabilitas dan likuiditas. Penelitian ini bersifat deskriptif kuantitatif. Populasi dalam penelitian ini meliputi seluruh laporan keuangan PT Bank BCA Syariah periode tahun 2013 sampai dengan 2017, sedangkan sampel dalam penelitian ini adalah laporan keuangan perusahaan berupa neraca dan laporan laba rugi PT. Bank BCA Syariah Tbk. periode 2013 sampai dengan 2017. Analisis data yang digunakan dalam penelitian ini adalah dengan menggunakan metode CAMEL yang terdiri dari lima aspek, yaitu aspek permodalan menggunakan rasio CAR (Capital Adequacy Ratio), aspek kualitas aktiva produktif menggunakan rasio KAP (Kualitas Aktiva Produktif) dan PPAP (Penyisihan Penghapusan Aktiva Produktif), aspek manajemen menggunakan rasio NPM (Net Profit Margin), aspek rentabilitas menggunakan rasio ROA (Return On Assets) dan BOPO (Beban Operasional terhadap Pendapatan Operasional), dan aspek likuiditas menggunakan rasio NCM-CA (Net Call Money to Current Assets) dan LDR (Loan to Deposit Ratio). Berdasarkan hasil penelitan yang telah dilakukan pada PT Bank BCA Syariah CAMEL pada tahun 2013 97,04 adalah sehat, tahun 2014 96,71 adalah sehat, tahun 2015 95,52 adalah sehat, tahun 2016 97,01 adalah sehat, tahun 2017 98,00 adalah sehat.

Kata Kunci : Rasio Tingkat Kesehatan Bank, CAMEL
LITERATURE REVIEW HUBUNGAN ANTARA TIPE KEPRIBADIAN DENGAN KEJADIAN HIPERTENSI
Authors: Rina Dede , Fitria Nita , Hendrawati Hendrawati
Published: February 2021

Hipertensi menurut WHO merupakan penyakit yang menimbulkan kesakitan dan kematian di seluruh dunia. Tipe kepribadian merupakan salah satu faktor yang menyebabkan terjadinya hipertensi. Deteksi dini terhadap tipe kepribadian diharapkan dapat menurunkan prevalensi hipertensi. Tujuan dari penelitian ini yaitu untuk mengetahui hubungan antara tipe kepribadian dengan kejadian hipertensi. Rancangan penelitian menggunakan studi literatur dari hasil penelitian yang dipublikasikan pada tahun 2010-2020. Pencarian literature menggunakan strategi dengan kata kunci tipe kepribadian dan hipertensi, menggunakan database Google Scholar dan Pubmed dengan kriteria yang digunakan yaitu judul artikel yang membahas tentang kaitannya hipertensi dengan tipe kepribadian, ketersediaan full text, sampel yang digunakan dalam artikel berdasarkan artikel yang akan di analisis yaitu pasien hipertensi dan tipe kepribadian, tahun terbit artikel maksimal 10 tahun terakhir. Hasil literature dari 10 artikel menggambarkan bahwa terdapat hubungan antara tipe kepribadian dengan kejadian hipertensi. Tipe kepribadian A dan tipe kepribadian sanguinis sangat mempengaruhi terjadinya hipertensi.
HUBUNGAN DURASI PENGGUNAAN GADGET TERHADAP PREVALENSI ASTIGMATISMA
Authors: Widia Chita , Nursobah Ayu , Darmono Darmono
Published: February 2021

Dampak negatif yang ditimbulkan dari seringnya mengakses layar monitor salah satunya adalah kelainan refraksi, hal ini sangat membatasi fungsi indera tersebut. Salah satu jenis kelainan refraksi adalah Astigmatisma dimana berkas cahaya tidak difokuskan pada satu titik dengan tajam pada retina.Tujuan penelitian ini dilakukan adalah untuk mengetahui hubungan antara durasi penggunaan gadget dengan prevalensi astigmatisma pada mahasiswa DIII Keperawatan STIKes Bakti Tunas Husada Tasikmalaya tahun 2020. Jenis penelitian yang digunakan adalah analitik kuantitatif dengan desain penelitian cross-sectional. Sampel dalam penelitian ini sebanyak 38 responden dengan teknik pengambilan sampel accidental sampling. Dalam penelitian ini, analisis variabel independen dan variabel dependen menggunakan uji pearson. Hasil penelitian diperoleh bahwa ada hubungan durasiÂ  penggunaan gadget dengan prevalensi astigmatisma pada mahasiswa TK 1 dan II prodi D III Keperawatan STIKes Bakti Tunas Husada Tasikmalaya nilai p (0,002) < Î± (0,05). Disarankan kepada seluruh pihak yang terkait agar tetap memperhatikan durasi penggunaan gadget.
Memutus Mata Rantai Penularan Virus Covid-19 melalui Penggunaan Masker dan Penggunaan Alat Dispenser Hand Sanitizer di Tempat Ibadah
Authors: Simbolon Veronika Amelia , Manullang Putri Orina , Sitanggang Yessica Efrioni
Published: February 2021

Penyakit korona merupakan penyakit dengan tingkat penularan yang cukup tinggi dan WHO telah menetapkan penyakit ini sebagai masalah kesehatan global (pandemik) dan Kedaruratan Kesehatan Masyarakat yang Meresahkan Dunia, sehingga perlu upaya perlindungan kesehatan masyarakat yang bertujuan untuk mencegah terjadinya penularan dalam skala luas. Tujuan kegiatan pengabdian masyarakat ini adalah untuk mengetahui kemauan dan kemampuan jemaat dalam melakukan pencegahan penularan virus corona bagi diri sendiri, keluarga maupun lingkungan. Metode kegiatan pengabdian kepada masyarakat yaitu sosialisasi dan himbauan kepada jemaat Gereja HKBP di Kota Tanjungpinang. Lokasi pelaksanaan pengabdian kepada masyarakat adalah Gereja HKBP Kota Tanjungpinang, Gereja HKBP Nomensen Melayu Kota Piring dan Gereja HKBP Bintan Center. Jumlah peserta dalam kegiatan ini adalah seluruh jemaat yang hadir saat ibadah berlangsung. Hasil kegiatan pengabdian masyarakat diketahui bahwa penerapan protokol kesehatan pada Gereja HKBP di Kota Tanjungpinang sudah sesuai anjuran pemerintah. Pihak gereja selalu menghimbau jemaat untuk tetap mematuhi protokol kesehatan. Sebagian besar jemaat sudah mematuhi protokol kesehatan, hanya sebagian kecil yang belum memahami aturan cara menggunakan masker dengan benar).
WDPCP Modulates Cilia Beating Through the MAPK/ERK Pathway in Chronic Rhinosinusitis With Nasal Polyps
Authors: Ma Yun , Tian Peng , Zhong Hua , Wu Fan , Zhang Qining , Liu Xiang , Dang Hua , Chen Qiujian , Zou Hua , Zheng Yiqing
Published: February 2021

Cilia loss and dysfunction is one of the typical pathological features of chronic rhinosinusitis with nasal polyps (CRSwNP). Tryptophan-aspartic acid (W-D) repeat containing planar cell polarity effector (WDPCP) has been proven to be an essential element for ciliogenesis in human nasal epithelium, but its role in the beating of cilia remains unclear. In this study, we sought to investigate the role of WDPCP and its underlying mechanism behind the dysfunction in the beating of cilia in nasal polyp tissue. We demonstrated WDPCP expression in the epithelium of nasal polyps. We also investigated the MAPK/ERK pathway in primary human sinonasal epithelial cells to explore the function of WDPCP. The air–liquid interface culture system was used as a model to verify the role of WDPCP and the MAPK/ERK pathway in the beating of cilia. With the dysfunction of cilia beating, we observed a low expression of WDPCP in the epithelium of nasal polyp tissues. Within the in vitro study, we found that WDPCP was critical for mitochondrial biogenesis and mitochondrial function in human sinonasal epithelial cells, possibly due to the activation of the MAPK/ERK pathway. The mitochondrial dysfunction caused by U0126 or lacking WDPCP could be partially recovered by dexamethasone. The low expression of WDPCP in nasal epithelium could affect mitochondria via the MAPK/ERK pathway, which may contribute to the dysfunction in the beating of cilia in CRSwNP.
The Role of the Cytoskeleton in Regulating the Natural Killer Cell Immune Response in Health and Disease: From Signaling Dynamics to Function
Authors: Ben-Shmuel Aviad , Sabag Batel , Biber Guy , Barda-Saad Mira
Published: February 2021

Natural killer (NK) cells are innate lymphoid cells, which play key roles in elimination of virally infected and malignant cells. The balance between activating and inhibitory signals derived from NK surface receptors govern the NK cell immune response. The cytoskeleton facilitates most NK cell effector functions, such as motility, infiltration, conjugation with target cells, immunological synapse assembly, and cytotoxicity. Though many studies have characterized signaling pathways that promote actin reorganization in immune cells, it is not completely clear how particular cytoskeletal architectures at the immunological synapse promote effector functions, and how cytoskeletal dynamics impact downstream signaling pathways and activation. Moreover, pioneering studies employing advanced imaging techniques have only begun to uncover the architectural complexity dictating the NK cell activation threshold; it is becoming clear that a distinct organization of the cytoskeleton and signaling receptors at the NK immunological synapse plays a decisive role in activation and tolerance. Here, we review the roles of the actin cytoskeleton in NK cells. We focus on how actin dynamics impact cytolytic granule secretion, NK cell motility, and NK cell infiltration through tissues into inflammatory sites. We will also describe the additional cytoskeletal components, non-muscle Myosin II and microtubules that play pivotal roles in NK cell activity. Furthermore, special emphasis will be placed on the role of the cytoskeleton in assembly of immunological synapses, and how mutations or downregulation of cytoskeletal accessory proteins impact NK cell function in health and disease.
ALMS1 Regulates TGF-β Signaling and Morphology of Primary Cilia
Authors: Álvarez-Satta María , Lago-Docampo Mauro , Bea-Mascato Brais , Solarat Carlos , Castro-Sánchez Sheila , Christensen Søren T. , Valverde Diana
Published: February 2021

In this study, we aimed to evaluate the role of ALMS1 in the morphology of primary cilia and regulation of cellular signaling using a knockdown model of the hTERT-RPE1 cell line. ALMS1 depletion resulted in the formation of longer cilia, which often displayed altered morphology as evidenced by extensive twisting and bending of the axoneme. Transforming growth factor beta/bone morphogenetic protein (TGF-β/BMP) signaling, which is regulated by primary cilia, was similarly affected by ALMS1 depletion as judged by reduced levels of TGFβ-1-mediated activation of SMAD2/3. These results provide novel information on the role of ALMS1 in the function of primary cilia and processing of cellular signaling, which when aberrantly regulated may underlie Alström syndrome.
Sunitinib and Imatinib Display Differential Cardiotoxicity in Adult Rat Cardiac Fibroblasts That Involves a Role for Calcium/Calmodulin Dependent Protein Kinase II
Authors: McMullen Calum J. , Chalmers Susan , Wood Rachel , Cunningham Margaret R. , Currie Susan
Published: February 2021

Background:Tyrosine kinase inhibitors (TKIs) have dramatically improved cancer treatment but are known to cause cardiotoxicity. The pathophysiological consequences of TKI therapy are likely to manifest across different cell types of the heart, yet there is little understanding of the differential adverse cellular effects. Cardiac fibroblasts (CFs) play a pivotal role in the repair and remodeling of the heart following insult or injury, yet their involvement in anti-cancer drug induced cardiotoxicity has been largely overlooked. Here, we examine the direct effects of sunitinib malate and imatinib mesylate on adult rat CF viability, Ca2+handling and mitochondrial function that may contribute to TKI-induced cardiotoxicity. In particular, we investigate whether Ca2+/calmodulin dependent protein kinase II (CaMKII), may be a mediator of TKI-induced effects.

Methods:CF viability in response to chronic treatment with both drugs was assessed using MTT assays and flow cytometry analysis. Calcium mobilization was assessed in CFs loaded with Fluo4-AM and CaMKII activationviaoxidation was measuredviaquantitative immunoblotting. Effects of both drugs on mitochondrial function was determined by live mitochondrial imaging using MitoSOX red.

Results:Treatment of CFs with sunitinib (0.1–10 μM) resulted in concentration-dependent alterations in CF phenotype, with progressively significant cell loss at higher concentrations. Flow cytometry analysis and MTT assays revealed increased cell apoptosis and necrosis with increasing concentrations of sunitinib. In contrast, equivalent concentrations of imatinib resulted in no significant change in cell viability. Both sunitinib and imatinib pre-treatment increased Angiotensin II-induced intracellular Ca2+mobilization, with only sunitinib resulting in a significant effect and also causing increased CaMKII activationviaoxidation. Live cell mitochondrial imaging using MitoSOX red revealed that both sunitinib and imatinib increased mitochondrial superoxide production in a concentration-dependent manner. This effect in response to both drugs was suppressed in the presence of the CaMKII inhibitor KN-93.

Conclusions:Sunitinib and imatinib showed differential effects on CFs, with sunitinib causing marked changes in cell viability at concentrations where imatinib had no effect. Sunitinib caused a significant increase in Angiotensin II-induced intracellular Ca2+mobilization and both TKIs caused increased mitochondrial superoxide production. Targeted CaMKII inhibition reversed the TKI-induced mitochondrial damage. These findings highlight a new role for CaMKII in TKI-induced cardiotoxicity, particularly at the level of the mitochondria, and confirm differential off-target toxicity in CFs, consistent with the differential selectivity of sunitinib and imatinib.
Insulin Therapy Is Associated With an Increased Risk of Carotid Plaque in Type 2 Diabetes: A Real-World Study
Authors: Ke Jiang-Feng , Wang Jun-Wei , Zhang Zhi-Hui , Chen Ming-Yun , Lu Jun-Xi , Li Lian-Xi
Published: February 2021

Background: Controversies concerning the association between insulin therapy and atherosclerotic lesions in type 2 diabetes mellitus (T2DM) remain to exist. The purpose of this study was to investigate whether insulin therapy in T2DM patients is linked with the increased risk of carotid atherosclerosis in real-world settings.

Methods: We retrospectively enrolled 2,356 hospitalized patients with T2DM, including 1,716 subjects receiving insulin therapy and 640 subjects without receiving insulin therapy. Carotid atherosclerotic lesions including carotid intima-media thickness (CIMT), carotid plaque and carotid stenosis were assessed by Doppler ultrasonography and were compared between T2DM patients treated with and without insulin.

Results: After adjusting for age and duration of diabetes, there was a significant increase in the prevalence of carotid plaque in both men (52.0 vs. 41.7%, p = 0.007) and women (49.6 vs. 39.7%, p = 0.003) receiving insulin therapy than in those without receiving insulin therapy. After further controlling for other confounding factors, compared with the patients without receiving insulin therapy, the risk of carotid plaque was still significantly increased not only in women treated with insulin (OR: 1.810; 95% CI: 1.155–2.837, p = 0.010), but also in men treated with insulin (OR: 1.867; 95% CI: 1.307–2.666; p = 0.001). Additionally, HOMA2-B% was higher in both women and men without receiving insulin therapy compared with those receiving insulin therapy (p < 0.001 in both men and women), but HOMA-IR was significantly higher in patients treated with insulin than in those without receiving insulin therapy (p < 0.001 in both men and women).

Conclusions: Insulin therapy is associated with markedly increased risk of carotid atherosclerotic lesions in type 2 diabetes, which partly attribute to the more serious insulin resistance in T2DM patients receiving insulin therapy.
Estimating a Sleep Apnea Hypopnea Index Based on the ERB Correlation Dimension of Snore Sounds
Authors: Hou Limin , Pan Qiang , Yi Hongliang , Shi Dan , Shi Xiaoyu , Yin Shankai
Published: February 2021

This paper proposes a new perspective of analyzing non-linear acoustic characteristics of the snore sounds. According to the ERB (Equivalent Rectangular Bandwidth) scale used in psychoacoustics, the ERB correlation dimension (ECD) of the snore sound was computed to feature different severity levels of sleep apnea hypopnea syndrome (SAHS). For the training group of 93 subjects, snore episodes were manually segmented and the ECD parameters of the snores were extracted, which established the gaussian mixture models (GMM). The nocturnal snore sound of the testing group of another 120 subjects was tested to detect SAHS snores, thus estimating the apnea hypopnea index (AHI), which is called AHIECD. Compared to the AHIPSG value of the gold standard polysomnography (PSG) diagnosis, the estimated AHIECD achieved an accuracy of 87.5% in diagnosis the SAHS severity levels. The results suggest that the ECD vectors can be effective parameters for screening SAHS.
Case Report: Novel RPGRIP1L Gene Mutations Identified by Whole Exome Sequencing in a Patient With Multiple Primary Tumors
Authors: Guo Jiani , Yang Yu , Ji Zhuqing , Yao Mengchu , Xia Xiaotian , Sha Xiaofeng , Huang Mingde
Published: February 2021

A 78 years old Chinese woman with five different cancer types and a family history of malignancy was the subject of this study. Pancreatic adenocarcinoma and gingival squamous cell carcinoma tissues were obtained from the patient and sequenced using Whole Exome Sequencing. Whole exome sequencing identified 20 mutation sites in six candidate genes. Sanger Sequencing was used for further validation. The results verified six mutations in three genes, OBSCN, TTN, and RPGRIP1L, in at least one cancer type. Immunohistochemistry was used to verify protein expression. mRNA expression analysis using The Cancer Genome Atlas database revealed that RPGRIP1L was highly expressed in several cancer types, especially in pancreatic adenocarcinoma, and correlated with patient survival and sensitivity to paclitaxel, probably through the TGF-β signaling pathway. The newly identified somatic mutations in RPGRIP1L might contribute to pathogenesis in the patients. Protein conformation simulation demonstrated that the alterations had caused the binding pocket at position 708 to change from concave to convex, which could restrict contraction and extension, and interfere with the physiological function of the protein. Further studies are required to determine the implication of RPGRIP1L in this family and in multiple primary tumors.
Identification of Tumor Microenvironment-Related Prognostic Genes in Sarcoma
Authors: Dai Dongjun , Xie Lanyu , Shui Yongjie , Li Jinfan , Wei Qichun
Published: February 2021

Aim

Immune cells that infiltrate the tumor microenvironment (TME) are associated with cancer prognosis. The aim of the current study was to identify TME related gene signatures related to the prognosis of sarcoma (SARC) by using the data from The Cancer Genome Atlas (TCGA).

Methods

Immune and stromal scores were calculated by estimation of stromal and immune cells in malignant tumor tissues using expression data algorithms. The least absolute shrinkage and selection operator (lasso) based cox model was then used to select hub survival genes. A risk score model and nomogram were used to predict the overall survival of patients with SARC.

Results

We selected 255 patients with SARC for our analysis. The Kaplan–Meier method found that higher immune (p = 0.0018) or stromal scores (p = 0.0022) were associated with better prognosis of SARC. The estimated levels of CD4+ (p = 0.0012) and CD8+ T cells (p = 0.017) via the tumor immune estimation resource were higher in patients with SARC with better overall survival. We identified 393 upregulated genes and 108 downregulated genes (p < 0.05, fold change >4) intersecting between the immune and stromal scores based on differentially expressed gene (DEG) analysis. The univariate Cox analysis of each intersecting DEG and subsequent lasso-based Cox model identified 11 hub survival genes (MYOC, NNAT, MEDAG, TNFSF14, MYH11, NRXN1, P2RY13, CXCR3, IGLV3-25, IGHV1-46, and IGLV2-8). Then, a hub survival gene-based risk score gene signature was constructed; higher risk scores predicted worse SARC prognosis (p < 0.0001). A nomogram including the risk scores, immune/stromal scores and clinical factors showed a good prediction value for SARC overall survival (C-index = 0.716). Finally, connectivity mapping analysis identified that the histone deacetylase inhibitors trichostatin A and vorinostat might have the potential to reverse the harmful TME for patients with SARC.

Conclusion

The current study provided new indications for the association between the TME and SARC. Lists of TME related survival genes and potential therapeutic drugs were identified for SARC.
Tumor Burden and Immunotherapy: Impact on Immune Infiltration and Therapeutic Outcomes
Authors: Kim Samuel I. , Cassella Christopher R. , Byrne Katelyn T.
Published: February 2021

Cancer immunotherapy has revolutionized the treatment landscape in medical oncology, but its efficacy has been variable across patients. Biomarkers to predict such differential response to immunotherapy include cytotoxic T lymphocyte infiltration, tumor mutational burden, and microsatellite instability. A growing number of studies also suggest that baseline tumor burden, or tumor size, predicts response to immunotherapy. In this review, we discuss the changes in immune profile and therapeutic responses that occur with increasing tumor size. We also overview therapeutic approaches to reduce tumor burden and favorably modulate the immune microenvironment of larger tumors.
A Synthesis of Deepwater Horizon Impacts on Coastal and Nearshore Living Marine Resources
Authors: Murawski Steven A. , Kilborn Joshua P. , Bejarano Adriana C. , Chagaris David , Donaldson David , Hernandez Frank J. , MacDonald Timothy C. , Newton Craig , Peebles Ernst , Robinson Kelly L.
Published: February 2021

The 2010 Deepwater Horizon (DWH) oil blowout in the Gulf of Mexico began on April 20, originating in the deep sea 66 km off the Louisiana coast. By early June, DWH oil had spread to coastal Louisiana, Mississippi, Alabama and western Florida. An estimated 2,113 km of shoreline were oiled, making DWH the largest marine oil spill in global history by length of affected shoreline. Additionally, a series of oil spill response measures were deployed, including diversions of Mississippi River discharge to forestall oil coming ashore, and the establishment of large-scale fishery closures, with both affecting coastal resources to varying degrees. Here, we review published studies and describe additional analyses evaluating long-term impacts of DWH on coastal/nearshore biological resources. We assembled time-series data collected by state, federal and academic partners on population abundance and environmental conditions to evaluate species and community change. Our study focused on plankton, invertebrates, fishes and dolphins, and 13 “key species” were selected to conduct semi-quantitative vulnerability-resilience (V-R) analyses. At one extreme, early life stages of Gulf Menhaden (Brevoortia patronus) were not affected due to seasonal spawning and larval development preceding the spill. In contrast, demographically independent populations of the common Bottlenose Dolphin, (Tursiops truncatus) suffered a variety of severe and ongoing health effects owing to oil exposure. Virtually all of the heavily oiled salt marsh habitat was in Louisiana, with the majority occurring in Barataria Bay. Multispecies trawl survey abundances declined post-DWH throughout eastern coastal Louisiana but remained stable elsewhere. A regime shift in composition of Barataria Bay trawl survey catches occurred during and following the spill, the persistence of which was associated with long-term reductions in average salinity and increases in water clarity. In some cases, fishery closures were associated with measurable but ephemeral increases in abundance of some targeted and bycatch species. Freshwater flooding of marshes was ineffective in preventing coastal oiling and severely affected benthic euryhaline resources including Eastern Oyster (Crassostrea virginica) and Marsh Periwinkle (Littoraria irrorata). The flooding response measure experiment also indicates the directionality of impacts that further planned water diversions may have on ecological communities of lower Mississippi River basins.
Horizontal and Vertical Movement Patterns and Habitat Use of Juvenile Porbeagles (Lamna nasus) in the Western North Atlantic
Authors: Skomal Gregory , Marshall Heather , Galuardi Benjamin , Natanson Lisa , Braun Camrin D. , Bernal Diego
Published: February 2021

The porbeagle (Lamna nasus) is a large, highly migratory endothermic shark broadly distributed in the higher latitudes of the Atlantic, South Pacific, and Indian Oceans. In the North Atlantic, the porbeagle has a long history of fisheries exploitation and current assessments indicate that this stock is severely overfished. Although much is known of the life history of this species, there is little fisheries-independent information about habitat preferences and ecology. To examine migratory routes, vertical behavior, and environmental associations in the western North Atlantic, we deployed pop-up satellite archival transmitting tags on 20 porbeagles in late November, 2006. The sharks, ten males and ten females ranging from 128 to 154 cm fork length, were tagged and released from a commercial longline fishing vessel on the northwestern edge of Georges Bank, about 150 km east of Cape Cod, MA. The tags were programmed to release in March (n = 7), July (n = 7), and November (n = 6) of 2007, and 17 (85%) successfully reported. Based on known and derived geopositions, the porbeagles exhibited broad seasonally-dependent horizontal and vertical movements ranging from minimum linear distances of 937 to 3,310 km and from the surface to 1,300 m, respectively. All of the sharks remained in the western North Atlantic from the Gulf of Maine, the Scotian Shelf, on George's Bank, and in the deep, oceanic waters off the continental shelf along the edge of, and within, the Gulf Stream. In general, the population appears to be shelf-oriented during the summer and early fall with more expansive offshore radiation in the winter and spring. Although sharks moved through temperatures ranging from 2 to 26°C, the bulk of their time (97%) was spent in 6-20°C. In the summer months, most of the sharks were associated with the continental shelf moving between the surface and the bottom and remaining < 200 m deep. In the late fall and winter months, the porbeagles moved into pelagic habitat and exhibited two behavioral patterns linked with the thermal features of the Gulf Stream: “non-divers” (n = 7) largely remained at epipelagic depths and “divers” (n = 10) made frequent dives into and remained at mesopelagic depths (200–1000 m). These data demonstrate that juvenile porbeagles are physiologically capable of exploiting the cool temperate waters of the western North Atlantic as well as the mesopelagic depths of the Gulf Stream, possibly allowing exploitation of prey not available to other predators.
Incidence of a First Thrombo-Embolic Event in Patients With Systemic Lupus Erythematosus and Anti-phosphatidylserine/prothrombin Antibodies: A Prospective Study
Authors: Sciascia Savino , Radin Massimo , Cecchi Irene , Rubini Elena , Foddai Silvia Grazietta , Barinotti Alice , Vaccarino Antonella , Rossi Daniela , Roccatello Dario
Published: February 2021

Objective: This study aimed to prospectively investigate the incidence of first thromboembolic events (TEs) in a cohort of systemic lupus erythematosus (SLE) patients. The patients were positive for anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and tested negative for anticardiolipin (aCL) and anti-β2–glycoprotein I (aβ2GPI) antibodies [regardless of their Lupus Anticoagulant (LA) status].

Methods: Inclusion criteria included: (a) SLE with no previous TEs; (b) no concomitant anti-thrombotic therapy; (c) isolated confirmed positive test for aPS/PT.

Results: From the total of 52 SLE patients (42, 80.8% women), 18 patients (34.6%) were found to be positive for aPS/PT (IgG/IgM). During a mean follow-up (3.9 ± 1.1 years), 3 TEs occurred (1.3%/year). The overall cumulative incidence of TEs was 5.8% after 2 years, and up to 16.7% when focusing on aPS/PT positive patients. All the TEs events (two cerebrovascular events and one thrombotic kidney microangiopathy) occurred in the aPS/PT positive group. When focusing on IgG aPS/PT, we found that patients who tested positive were at a significantly higher risk for TEs (crude HR 19.6, 95%; CI 1.1 to 357.6; p < 0.05) compared to patients with negative aPS/PT.

Conclusion: This study observed a rate of TEs of 1.3%/year, in aPS/PT positive only patients. Our prospective data suggest that aPS/PT might confer an increased risk for the development of TEs in SLE patients.
Genome-Wide Analyses of Repeat-Induced Point Mutations in the Ascomycota
Authors: van Wyk Stephanie , Wingfield Brenda D. , De Vos Lieschen , van der Merwe Nicolaas A. , Steenkamp Emma T.
Published: February 2021

The Repeat-Induced Point (RIP) mutation pathway is a fungus-specific genome defense mechanism that mitigates the deleterious consequences of repeated genomic regions and transposable elements (TEs). RIP mutates targeted sequences by introducing cytosine to thymine transitions. We investigated the genome-wide occurrence and extent of RIP with a sliding-window approach. Using genome-wide RIP data and two sets of control groups, the association between RIP, TEs, and GC content were contrasted in organisms capable and incapable of RIP. Based on these data, we then set out to determine the extent and occurrence of RIP in 58 representatives of the Ascomycota. The findings were summarized by placing each of the fungi investigated in one of six categories based on the extent of genome-wide RIP.In silicoRIP analyses, using a sliding-window approach with stringent RIP parameters, implemented simultaneously within the same genetic context, on high quality genome assemblies, yielded superior results in determining the genome-wide RIP among the Ascomycota. Most Ascomycota had RIP and these mutations were particularly widespread among classes of the Pezizomycotina, including the early diverging Orbiliomycetes and the Pezizomycetes. The most extreme cases of RIP were limited to representatives of the Dothideomycetes and Sordariomycetes. By contrast, the genomes of the Taphrinomycotina and Saccharomycotina contained no detectable evidence of RIP. Also, recent losses in RIP combined with controlled TE proliferation in the Pezizomycotina subphyla may promote substantial genome enlargement as well as the formation of sub-genomic compartments. These findings have broadened our understanding of the taxonomic range and extent of RIP in Ascomycota and how this pathway affects the genomes of fungi harboring it.
Developing Innolysins Against Campylobacter jejuni Using a Novel Prophage Receptor-Binding Protein
Authors: Zampara Athina , Sørensen Martine C. Holst , Gencay Yilmaz Emre , Grimon Dennis , Kristiansen Sebastian Hougaard , Jørgensen Lallana Skaarup , Kristensen Josephine Rejgaard , Briers Yves , Elsser-Gravesen Anne , Brøndsted Lone
Published: February 2021

Campylobacter contaminated poultry remains the major cause of foodborne gastroenteritis worldwide, calling for novel antibacterials. We previously developed the concept of Innolysin composed of an endolysin fused to a phage receptor binding protein (RBP) and provided the proof-of-concept that Innolysins exert bactericidal activity against Escherichia coli. Here, we have expanded the Innolysin concept to target Campylobacter jejuni. As no C. jejuni phage RBP had been identified so far, we first showed that the H-fiber originating from a CJIE1-like prophage of C. jejuni CAMSA2147 functions as a novel RBP. By fusing this H-fiber to phage T5 endolysin, we constructed Innolysins targeting C. jejuni (Innolysins Cj). Innolysin Cj1 exerts antibacterial activity against diverse C. jejuni strains after in vitro exposure for 45 min at 20°C, reaching up to 1.30 ± 0.21 log reduction in CAMSA2147 cell counts. Screening of a library of Innolysins Cj composed of distinct endolysins for growth inhibition, allowed us to select Innolysin Cj5 as an additional promising antibacterial candidate. Application of either Innolysin Cj1 or Innolysin Cj5 on chicken skin refrigerated to 5°C and contaminated with C. jejuni CAMSA2147 led to 1.63 ± 0.46 and 1.18 ± 0.10 log reduction of cells, respectively, confirming that Innolysins Cj can kill C. jejuni in situ. The receptor of Innolysins Cj remains to be identified, however, the RBP component (H-fiber) recognizes a novel receptor compared to lytic phages binding to capsular polysaccharide or flagella. Identification of other unexplored Campylobacter phage RBPs may further increase the repertoire of new Innolysins Cj targeting distinct receptors and working as antibacterials against Campylobacter.
Factors Associated With Short-Term Eradication of Rectal Colonization by KPC-2 Producing Klebsiella pneumoniae in an Outbreak Setting
Authors: Pellicé Martina , Rodríguez-Núñez Olga , Rico Verónica , Agüero Daiana , Morata Laura , Cardozo Celia , Puerta-Alcalde Pedro , Garcia-Vidal Carolina , Rubio Elisa , Fernandez-Pittol Mariana J. , Vergara Andrea , Pitart Cristina , Marco Francesc , Santana Gemina , Rodríguez-Serna Laura , Vilella Ana , López Ester , Soriano Alex , Martínez Jose Antonio , Del Rio Ana
Published: February 2021

Background: KPC-producing Klebsiella pneumoniae (KPCKP) is a threat for patients admitted to healthcare institutions.

Objectives: To assess the efficacy of several decolonization strategies for KPCKP rectal carriage.

Methods: Observational study performed in a 750-bed university center from July to October 2018 on the efficacy of a 10-day non-absorbable oral antibiotic (NAA) regimen (colistin 10 mg/ml, amikacin 8 mg/ml, and nystatin 30 mg/ml, 10 ml/6 h) vs. the same regimen followed by a probiotic (Vivomixx®) for 20 days in adult patients with KPCKP rectal colonization acquired during an outbreak.

Results: Seventy-three patients colonized by KPCKP were included, of which 21 (29%) did not receive any treatment and 52 (71.2%) received NAA either alone (n = 26, 35.6%) or followed by a probiotic (n = 26, 35.6%). Eradication was observed in 56 (76.7%) patients and the only variable significantly associated with it was not receiving systemic antibiotics after diagnosis of rectal carriage [22/24 (91.6%) vs. 34/49 (69.3%), p = 0.04]. Eradication in patients receiving NAA plus probiotic was numerically but not significantly higher than that of controls [23/26 (88.4%) vs. 15/21 (71.4%), p = 0.14] and of those receiving only NAA (OR = 3.4, 95% CI = 0.78–14.7, p = 0.09).

Conclusion: In an outbreak setting, rectal carriage of KPCKP persisted after a mean of 36 days in about one quarter of patients. The only factor associated with eradication was not receiving systemic antibiotic after diagnosis. A 10-day course of NAA had no impact on eradication. Probiotics after NAA may increase the decolonization rate, hence deserving further study.
Protein Stability Perturbation Contributes to the Loss of Function in Haploinsufficient Genes
Authors: Birolo Giovanni , Benevenuta Silvia , Fariselli Piero , Capriotti Emidio , Giorgio Elisa , Sanavia Tiziana
Published: February 2021

Missense variants are among the most studied genome modifications as disease biomarkers. It has been shown that the “perturbation” of the protein stability upon a missense variant (in terms of absolute ΔΔG value, i.e., |ΔΔG|) has a significant, but not predictive, correlation with the pathogenicity of that variant. However, here we show that this correlation becomes significantly amplified in haploinsufficient genes. Moreover, the enrichment of pathogenic variants increases at the increasing protein stability perturbation value. These findings suggest that protein stability perturbation might be considered as a potential cofactor in diseases associated with haploinsufficient genes reporting missense variants.
Microstructural and Cerebral Blood Flow Abnormalities in Subjective Cognitive Decline Plus: Diffusional Kurtosis Imaging and Three-Dimensional Arterial Spin Labeling Study
Authors: Yang Zhongxian , Rong Yu , Cao Zhen , Wu Yi , Zhao Xinzhu , Xie Qiuxia , Luo Min , Liu Yubao
Published: February 2021

Objective: To explore microstructural and cerebral blood flow (CBF) abnormalities in individuals with subjective cognitive decline plus (SCD plus) using diffusional kurtosis imaging (DKI) and three-dimensional (3D) arterial spin labeling (ASL).

Methods: Twenty-seven patients with SCD plus, 31 patients with amnestic mild cognitive impairment (aMCI), and 33 elderly controls (ECs) were recruited and underwent DKI and 3D ASL using a GE 3.0-T MRI. Mean kurtosis (MK), fractional anisotropy (FA), mean diffusivity (MD), and CBF values were acquired from 24 regions of interest (ROIs) in the brain, including the bilateral hippocampal (Hip) subregions (head, body, and tail), posterior cingulate cortex (PCC), precuneus, dorsal thalamus subregions (anterior nucleus, ventrolateral nucleus, and medial nucleus), lenticular nucleus, caput nuclei caudati, white matter (WM) of the frontal lobe, and WM of the occipital lobe. Pearson's correlation analysis was performed to assess the relationships among the DKI-derived parameters, CBF values, and key neuropsychological tests for SCD plus.

Results: Compared with ECs, participants with SCD plus showed a significant decline in MK and CBF values, mainly in the Hip head and PCC, and participants with aMCI exhibited more significant abnormalities in the MK and CBF values than individuals with ECs and SCD plus in multiple regions. Combined MK values showed better discrimination between patients with SCD plus and ECs than that obtained using CBF levels, with areas under the receiver operating characteristic (ROC) curve (AUC) of 0.874 and 0.837, respectively. Similarly, the AUC in discriminating SCD plus from aMCI patients obtained using combined MK values was 0.823, which was also higher than the combined AUC of 0.779 obtained using CBF values. Moreover, MK levels in the left Hip (h) and left PCC positively correlated with the auditory verbal learning test-delayed recall (AVLT-DR) score in participants with SCD plus. By contrast, only the CBF value in the left Hip head positively correlated with the AVLT-DR score.

Conclusions: Our results provide new evidence of microstructural and CBF changes in patients with SCD plus. MK may be used as an early potential neuroimaging biomarker and may be a more sensitive DKI parameter than CBF at the very early stage of Alzheimer's disease (AD).
High Diagnostic Utility Incorporating a Targeted Neurodegeneration Gene Panel With MRI Brain Diagnostic Algorithms in Patients With Young-Onset Cognitive Impairment With Leukodystrophy
Authors: Chen Zhiyong , Tan Yi Jayne , Lian Michelle M. , Tandiono Moses , Foo Jia Nee , Lim Weng Khong , Kandiah Nagaendran , Tan Eng-King , Ng Adeline S. L.
Published: February 2021

Leukodystrophies are a diverse group of genetic disorders that selectively involve the white matter of the brain and are a frequent cause of young-onset cognitive impairment. Genetic diagnosis is challenging. Data on the utility of incorporating brain magnetic resonance imaging (MRI) diagnostic algorithms with next-generation sequencing (NGS) for diagnosis in a real-life clinical setting is limited. We performed sequencing using a custom-designed panel of 200 neurodegeneration-associated genes on 45 patients with young-onset cognitive impairment with leukodystrophy, and classified them based on van der Knaap et al.'s MRI diagnostic algorithm. We found that 20/45 (44.4%) patients carried pathogenic variants or novel variants predicted to be pathogenic (one in CSF1R, two in HTRA1 and 17 in NOTCH3). All patients with an established genetic diagnosis had an MRI brain pattern consistent with a specific genetic condition/s. More than half (19/37, 51.4%) of patients with MRI changes consistent with vascular cognitive impairment secondary to small vessel disease (VCI-SVD) had pathogenic variants, including all patients with pathogenic NOTCH3 (17/19, 89.5%) and HTRA1 variants (2/19, 11.5%). Amongst patients harboring pathogenic NOTCH3 variants, 13/17 (76.5%) carried the p.R544C variant seen predominantly in East Asians. Anterior temporal white matter involvement was seen only in patients with pathogenic NOTCH3 variants (6/17, 35.3%). Overall, we demonstrated a high diagnostic utility incorporating a targeted neurodegeneration gene panel and MRI-based diagnostic algorithms in young-onset cognitive impairment patients with leukodystrophy.