bluuebunny/crossref_metadata_2025 huggingface dataset:
Metode Absensi Mahasiswa berbasis QR Code dan Time-Based One-Time Password
Authors: Sari Aprianti Nanda , Abdillah Trisna Gelar
Published: February 2021

Sistem absensi manual dengan cara memanggil nama mahasiswa satu persatu oleh dosen atau dengan menandatangani list kehadiran tentunya akan memakan waktu yang cukup lama dan tidak aman. Maka dibangunlah sistem absensi terkomputerisasi berbasis sidik jari, RFID, pengenalan wajah dan lainnya. Akan tetapi metode-metode tersebut memerlukan biaya tambahan untuk membeli alat khusus. Sebagai solusi, akhirnya sistem absensi berbasis QR code semakin diminati karena hanya memerlukan webcam bawaan dari laptop atau PC. Mahasiswa yang hadir di kelas hanya butuh memindai QR code yang tertera pada saat kelas berlangsung melalui smartphone mereka sebagai tanda kehadiran. Akan tetapi sistem absensi berbasis QR code ini memiliki celah misalnya mahasiswa yang hadir dapat mengambil gambar dan mengirimkan QR code di kelas kepada temannya yang tidak hadir agar dapat dianggap hadir. Sehingga diperlukan sistem autentikasi dengan keamanan tambahan agar kecurangan pada sistem absensi berbasis QR code tidak terjadi. Salah satu upayanya adalah dengan menggunakan One-Time Password yang dibuat unik dan dinamis untuk setiap mahasiswa dan hanya berlaku sekali saja dalam waktu singkat saja atau yang lebih dikenal sebagai Time-based One-Time Password atau disingkat TOTP. Dari hasil analisa, penggunaan TOTP dapat menghindari berbagai kemungkinan kecurangan oleh mahasiswa dan penyerangan oleh pihak ketiga.
Sistem Prediksi Permintaan Darah Menggunakan Metode Regresi Linier
Authors: Sumari Arwin Datumaya Wahyudi , Adhika Febrianto  , Yushintia Pramitarini
Published: February 2021

Stok darah merupakan salah satu faktor kritis bagi sebuah Unit Transfusi Darah (UTD) yang melayani permintaan darah dari berbagai pihak yang membutuhkan. Peran UTD sebagai penyelenggara pelayanan darah menuntut unit kesehatan tersebut mampu memenuhi kebutuhan karena terkait erat dengan kesehatan dan keselamatan nyawa seseorang. Salah satu permasalahan penting yang dihadapi UTD adalah ketidakpastian permintaan darah sehingga diperlukan cara untuk menjamin ketersediaannya. Hal ini dikarenakan sifat darah yang tidak menentu (perishable) dan tidak dapat diproduksi kembali, serta ketersediaannya yang sangat bergantung pada pendonor darah sukarela. Dalam upaya memberikan solusi, dalam penelitian ini telah dibangun sebuah sistem prediksi persediaan darah menggunakan metode Regresi Linier dengan studi kasus di UTD PMI Kabupaten Bojonegoro pada data-data terkait produk darah Whole Blood (WB) pada semua jenis golongan darah yakni A, B, O, dan AB. Dari pengujian akurasi prediksi menggunakan metode Mean Absolute Percentage Error (MAPE) diperoleh hasil-hasil prediksi yakni produk darah WB golongan A dengan MAPE 18,74% atau Baik, produk darah WB golongan B dengan MAPE 24,37% atau Masuk Akal, produk darah WB golongan O dengan MAPE 17,66% atau Baik, dan produk darah WB golongan AB dengan nilai MAPE 18,67% atau Baik. Sistem prediksi permintaan darah berbasis Regresi Linier ini mampu menunjukkan kinerja dengan rata-rata akurasi prediksi sebesar 80,14% dan dari sisi MAPE diinterpretasikan sebagai prediksi Baik.
Cost Sensitive Tree dan Naïve Bayes pada Klasifikasi Multiclass
Authors: Febriantono M. Aldiki , Ridho Herasmara  , Gusti Pangestu
Published: February 2021

Data mining merupakan proses pengolahan data untuk mengambil keputusan secara cepat, tepat dan akurat. Data mining pada bidang kesehatan dan manufacturing menjadi hal yang sangat penting dikarenakan suatu kesalahan klasifikasi (misclassification) akan memiliki dampak serius. Masalah utama pada data mining ketika data yang digunakan bersifat imbalanced multiclass karena classifier kesulitan untuk mengklasifikasikan data sehingga menyebabkan terjadinya misclassification. Solusi untuk meminimalkan missclasification dengan menggunakan metode cost sensitive pada classifier decision tree C5.0 dan naïve bayes. Penelitian ini menggunakan dataset glass, lympografi, vehicle, thyroid dan wine yang diperoleh dari UCI Respository. Kelima dataset dilakukan proses seleksi atribut menggunakan particle swarm optimazation. Kemudian dataset diuji menggunakan metode cost sensitive decision tree C5.0 dan cost sensitive naïve bayes. Hasil pengujian menggunakan metode cost sensitive decision tree C5.0 diperoleh nilai accuracy pada dataset glass, lympografi, vehicle, thyroid dan wine berturut-turut sebesar 76.17%, 83.33%, 75.27%, 95.81% dan 95.83%. Sedangkan metode cost sensitive naïve bayes memiliki performa accuracy pada dataset berturut-turut sebesar 32.24%, 82.61%, 25.53%, 97.67% dan 94.94%.
Pneumonia Identifikasi Pneumonia Pada Citra Rontgen Paru Menggunakan Metode Power-Law Trans
Authors: Kadek Batubulan  , Ridwan Rismanto
Published: February 2021

Pneumonia  adalah  proses  infeksi  akut  yang  mengenai  jaringan  paru-paru  (Alveoli),  yang  dapat disebabkan  oleh  infeksi  jasad  renik  atau  bakteri.  Deteksi  penyakit  Pneumonia  dilakukan  melalui  tanda-tanda klinis uji laboratorium dan foto x-ray paru. Penelitian ini menggunakan beberapa langkah dari pengolahan citra, seperti Power-law  trans, Gabor  Waveletdan Boundary.  Tujuan  utama  dari  langkah  tersebut  adalah  untuk mengidentifikasi infiltrate dari  citra  X-Ray  paru–paru  manusia  dan  menentukan  klasifikasi infiltrate.  Hasil penelitian  mengindikasikan  klasifikasi  dari  penyakit pneumonia menjadi  normal, pneumonia ringan,  dan pneumonia kronik. Pengujian  dilakukan  pada  lima  puluh  citra  dengan  spesifikasi  yang  berbeda.  Dari  hasil pengujian  tersebut,  menunjukkan  bahwa  equivD  dan  perimeter  rata-rata infiltrate ditiap  citra  yang  bernilai dibawah 30 diidentifikasi sebagai penyakit pneumonia. Diidentifikasi pneumonia kronik apabila rata-rata equivD dan perimeter infiltrate diatas 30. Untuk identifikasi normal apabila centroid, equivD, perimeter dan roundness tidak  ada. Validitas sistem dinilai  dengan  cara  menghitung nilai  TP,  TN,  FP,  dan  FN  sehingga  di  dapatkan Sensitivity dari metode ini adalah 94,3% dan Specificity dari sistem ini adalah 100%.
Structured Sparsity of Convolutional Neural Networks via Nonconvex Sparse Group Regularization
Authors: Bui Kevin , Park Fredrick , Zhang Shuai , Qi Yingyong , Xin Jack
Published: February 2021

Convolutional neural networks (CNN) have been hugely successful recently with superior accuracy and performance in various imaging applications, such as classification, object detection, and segmentation. However, a highly accurate CNN model requires millions of parameters to be trained and utilized. Even to increase its performance slightly would require significantly more parameters due to adding more layers and/or increasing the number of filters per layer. Apparently, many of these weight parameters turn out to be redundant and extraneous, so the original, dense model can be replaced by its compressed version attained by imposing inter- and intra-group sparsity onto the layer weights during training. In this paper, we propose a nonconvex family of sparse group lasso that blends nonconvex regularization (e.g., transformed ℓ1, ℓ1−ℓ2, and ℓ0) that induces sparsity onto the individual weights and ℓ2,1 regularization onto the output channels of a layer. We apply variable splitting onto the proposed regularization to develop an algorithm that consists of two steps per iteration: gradient descent and thresholding. Numerical experiments are demonstrated on various CNN architectures showcasing the effectiveness of the nonconvex family of sparse group lasso in network sparsification and test accuracy on par with the current state of the art.
What Is the Next Generation of Transcatheter Mitral Valve Repair Devices?
Authors: Chen Mi , Sun Lizhong
Published: February 2021

In the evolving scenario of the transcatheter mitral valve repair (TMVr), TMVr devices constitute a rapidly expanding field. The standard classification includes edge-to-edge repair, direct annuloplasty, indirect annuloplasty, chordal/papillary muscular repair, and the others. However, the unknowns and uncertainties to innovate a high-performing device are addressed. In this viewpoint, the authors discuss the potential future of the next generation and the challenges of TMVr devices.
Local Explosion Detection and Infrasound Localization by Reverse Time Migration Using 3-D Finite-Difference Wave Propagation
Authors: Fee David , Toney Liam , Kim Keehoon , Sanderson Richard W. , Iezzi Alexandra M. , Matoza Robin S. , De Angelis Silvio , Jolly Arthur D. , Lyons John J. , Haney Matthew M.
Published: February 2021

Infrasound data are routinely used to detect and locate volcanic and other explosions, using both arrays and single sensor networks. However, at local distances (<15 km) topography often complicates acoustic propagation, resulting in inaccurate acoustic travel times leading to biased source locations when assuming straight-line propagation. Here we present a new method, termed Reverse Time Migration-Finite-Difference Time Domain (RTM-FDTD), that integrates numerical modeling into the standard RTM back-projection process. Travel time information is computed across the entire potential source grid via FDTD modeling to incorporate the effects of topography. The waveforms are then back-projected and stacked at each grid point, with the stack maximum corresponding to the likely source. We apply our method to three volcanoes with different network configurations, source-receiver distances, and topography. At Yasur Volcano, Vanuatu, RTM-FDTD locates explosions within ∼20 m of the source and differentiates between multiple vents. RTM-FDTD produces a more accurate location for the two Yasur subcraters than standard RTM and doubles the number of detected events. At Sakurajima Volcano, Japan, RTM-FDTD locates the source within 50 m of the active vent despite notable topographic blocking. The RTM-FDTD location is similar to that from the Time Reversal Mirror method, but is more computationally efficient. Lastly, at Shishaldin Volcano, Alaska, RTM and RTM-FDTD both produce realistic source locations (<50 m) for ground-coupled airwaves recorded on a four-station seismic network. We show that RTM is an effective method to detect and locate infrasonic sources across a variety of scenarios, and by integrating numerical modeling, RTM-FDTD produces more accurate source locations and increases the detection capability.
Using Single-Cell RNA-Seq Data to Trace Tissue Cells Responsive to Thyroid Hormones
Authors: Hu Liang , Wu Chao
Published: February 2021

Thyroid hormones mediate a remarkable range of functions in many tissues and organ systems through the thyroid hormone receptors—THRA and THRB. Tissues and organs are composed of heterogeneous cells of different cell types. These different cell types have varying receptor expression abilities, which lead to variable responses in thyroid hormone regulation. The tissue-specific Thra and Thrb gene expression patterns help us understand the action of thyroid hormones at the tissue level. However, the situation becomes complicated if we wish to focus on tissues more closely to trace the responsive cells, which is a vital step in the process of understanding the molecular mechanism of diseases related to thyroid hormone regulation. Single-cell RNA sequencing technology is a powerful tool used to profile gene expression programs in individual cells. The Tabula Muris Consortium generates a single-cell transcriptomic atlas across the life span of Mus musculus that includes data from 23 tissues and organs. It provides an unprecedented opportunity to understand thyroid hormone regulation at the cell type resolution. We demonstrated the approaches that allow application of the single-cell RNA-Seq data generated by the Tabula Muris Consortium to trace responsive cells in tissues. First, employing the single-cell RNA-Seq data, we calculated the ability of different cell types to express Thra and Thrb, which direct us to the cell types sensitive to thyroid hormone regulation in tissues and organs. Next, using a cell clustering algorithm, we explored the subtypes with low Thra or Thrb expression within the different cell types and identified the potentially responsive cell subtypes. Finally, in the liver tissue treated with thyroid hormones, using the single-cell RNA-Seq data, we successfully traced the responsive cell types. We acknowledge that the computational predictions reported here need to be further validated using wet-lab experiments. However, we believe our results provide powerful information and will be beneficial for wet lab researchers.
First Evidence of a Relationship Between Female Major Histocompatibility Complex Diversity and Eggshell Bacteria in House Sparrows (Passer domesticus)
Authors: Darolová Alžbeta , Poláček Miroslav , Krištofík Ján , Lukasch Barbara , Hoi Herbert
Published: February 2021

Bacteria are known to exert positive and negative influences on animals’ health and fitness. Bacteria, in particular those inhabiting the skin and inner organs of vertebrates, are horizontally or vertically transmitted. Specifically, mothers of bird species can transfer bacterial strains to their offspring when the egg is passing the reproductive tract, as the eggshell rubs against the wall of the uterus. In this context, the female immune system might play an important role in influencing the vertical transmission of bacteria. Here, we investigate the relationship between the major histocompatibility complex (MHC) and cultivable eggshell bacteria originating putatively from the female urogenital tract in a captive population of house sparrows (Passer domesticus). We predict that females with a more variable MHC will transfer fewer bacteria onto the eggshells. Our results show a negative relationship between the number of functional MHC class I alleles and bacteria originating in the urinary tract and growing on a selective medium. This is the first study to find a correlation between female MHC diversity and eggshell bacteria.
Infection of the Stable Fly, Stomoxys calcitrans, L. 1758 (Diptera: Muscidae) by the Entomopathogenic Fungi Metarhizium anisopliae (Hypocreales: Clavicipitaceae) Negatively Affects Its Survival, Feeding Propensity, Fecundity, Fertility, and Fitness Parameters
Authors: Baleba Steve B. S. , Agbessenou Ayaovi , Getahun Merid N. , Akutse Komivi S. , Subramanian Sevgan , Masiga Daniel
Published: February 2021

Entomopathogenic fungi can cause substantial mortality in harmful insects. Before killing the insect, these pathogens start by negatively affecting the biological parameters of the host. Prior to our study, the information about how fungal exposure affects the biological parameters of the stable fly, Stomoxys calcitrans was still elusive. Therefore, we aimed to assess the infection of S. calcitrans with some Metarhizium anisopliae strains, and their impact on feeding, fecundity, fertility and other life-history traits of this fly. Among the 11 M. anisopliae strains screened, we identified ICIPE 30 as the most virulent strain against S. calcitrans. We observed that the infectivity of this strain was sex and age-dependent. Infected male S. calcitrans died earlier than their counterpart females. Older infected S. calcitrans died faster than infected young ones. Also, male and female S. calcitrans successfully transmitted ICIPE 30 conidia to their mates. We demonstrated that infection by ICIPE 30 extended the feeding time of S. calcitrans and consequently reduced the feeding probability of the fly and the amount of blood taken. Using a dual test oviposition bioassay, we determined that uninfected gravid female S. calcitrans avoided laying eggs on substrates amended with ICIPE 30 conidia. We showed that these conidia could lower the hatchability of the eggs deposited by gravid females. Using, a no-choice test, we showed that gravid female S. calcitrans infected with ICIPE 30 laid fewer eggs than uninfected females and those eggs hatched less. Using 11 strains of M. anisopliae and four high concentrations of ICIPE 30 conidia, we verified that S. calcitrans larvae were not susceptible to fungal infection. Further, we showed that though these larvae were tolerant to fungal infection, there was a significant effect on their fitness, with contaminated larvae having a small bodyweight coupled with longer developmental time as compared to uncontaminated larvae. Our study provides detailed information on how fungal infection affects the biology of S. calcitrans and the potential of using M. anisopliae ICIPE 30 as a biopesticide to reduce the fly population. Such knowledge can assist in developing fungal-based control strategies against this harmful fly.
Pinpointing the PRDM9-PRDM7 Gene Duplication Event During Primate Divergence
Authors: Heerschop Sacha , Fagrouch Zahra , Verschoor Ernst J. , Zischler Hans
Published: February 2021

Studies on the function of PRDM9 in model systems and its evolution during vertebrate divergence shed light on the basic molecular mechanisms of hybrid sterility and its evolutionary consequences. However, information regarding PRDM9-homolog, PRDM7, whose origin is placed in the primate evolutionary tree, as well as information about the fast-evolving DNA-binding zinc finger array of strepsirrhine PRDM9 are scarce. Thus, we aimed to narrow down the date of the duplication event leading to the emergence of PRDM7 during primate evolution by comparing the phylogenetic tree reconstructions of representative primate samples of PRDM orthologs and paralogs. To confirm our PRDM7 paralogization pattern, database-deposited sequences were used to test the presence/absence patterns expected from the paralogization timing. In addition, we extended the existing phylogenetic tree of haplorrhine PRDM9 zinc fingers with their strepsirrhine counterparts. The inclusion of strepsirrhine zinc fingers completes the PRDM9 primate phylogeny. Moreover, the updated phylogeny of PRDM9 zinc fingers showed distinct clusters of strepsirrhine, tarsier, and anthropoid degenerated zinc fingers. Here, we show that PRDM7 emerged on the branch leading to the most recent common ancestor of catarrhines; therefore, its origin is more recent than previously expected. A more detailed character evolutionary study suggests that PRDM7 may have evolved differently in Cercopithecoidea as compared to Hominoidea: it lacks the first four exons in Old World monkeys orthologs and exon 10 in Papionini orthologs. Dating the origin of PRDM7 is essential for further studies investigating why Hominoidea representatives need another putative histone methyltransferase in the testis.
Common and Rare Variants Genetic Association Analysis of Circulating Neutrophil Extracellular Traps
Authors: Donkel Samantha J. , Portilla Fernández Eliana , Ahmad Shahzad , Rivadeneira Fernando , van Rooij Frank J. A. , Ikram M. Arfan , Leebeek Frank W. G. , de Maat Moniek P. M. , Ghanbari Mohsen
Published: February 2021

Introduction

Neutrophils contribute to host defense through different mechanisms, including the formation of neutrophil extracellular traps (NETs). The genetic background and underlying mechanisms contributing to NET formation remain unclear.

Materials and Methods

We performed a genome-wide association study (GWAS) and exome-sequencing analysis to identify common and rare genetic variants associated with plasma myeloperoxidase (MPO)-DNA complex levels, a biomarker for NETs, in the population-based Rotterdam Study cohort. GWAS was performed using haplotype reference consortium(HRC)-imputed genotypes of common variants in 3,514 individuals from the first and 2,076 individuals from the second cohort of the Rotterdam Study. We additionally performed exome-sequencing analysis in 960 individuals to investigate rare variants in candidate genes.

Results

The GWAS yielded suggestive associations (p-value < 5.0 × 10−6) of SNPs annotated to four genes. In the exome-sequencing analysis, a variant in TMPRSS13 gene was significantly associated with MPO-DNA complex levels (p-value < 3.06×10−8). Moreover, gene-based analysis showed ten genes (OR10H1, RP11-461L13.5, RP11-24B19.4, RP11-461L13.3, KHDRBS1, ZNF200, RP11-395I6.1, RP11-696P8.2, RGPD1, AC007036.5) to be associated with MPO-DNA complex levels (p-value between 4.48 × 10−9 and 1.05 × 10−6). Pathway analysis of the identified genes showed their involvement in cellular development, molecular transport, RNA trafficking, cell-to-cell signaling and interaction, cellular growth and proliferation. Cancer was the top disease linked to the NET-associated genes.

Conclusion

In this first GWAS and exome-sequencing analysis of NETs levels, we found several genes that were associated with NETs. The precise mechanism of how these genes may contribute to neutrophil function or the formation of NETs remains unclear and should be further investigated in experimental studies.
Combined Immunotherapy With Belatacept and BTLA Overexpression Attenuates Acute Rejection Following Kidney Transplantation
Authors: Zhang Hengcheng , Wang Zijie , Zhang Jiayi , Gui Zeping , Han Zhijian , Tao Jun , Chen Hao , Sun Li , Fei Shuang , Yang Haiwei , Tan Ruoyun , Chandraker Anil , Gu Min
Published: February 2021

Background

Costimulatory blockade provides new therapeutic opportunities for ensuring the long-term survival of kidney grafts. The adoption of the novel immunosuppressant Belatacept has been limited, partly due to concerns regarding higher rates and grades of acute rejection in clinical trials. In this study, we hypothesized that a combined therapy, Belatacept combined with BTLA overexpression, may effectively attenuate acute rejection after kidney transplantation.

Materials and Methods

The rat kidney transplantation model was used to investigate graft rejection in single and combined therapy. Graft function was analyzed by detecting serum creatinine. Pathological staining was used to observe histological changes in grafts. The expression of T cells was observed by immunohistochemistry and flow cytometry.In vitro, we constructed an antigen-stimulated immune response by mixed lymphocyte culture, treated with or without Belatacept and BTLA-overexpression adenovirus, to observe the proliferation of receptor cells and the expression of cytokines. In addition, western blot and qRT-PCR analyses were performed to evaluate the expression of CTLA-4 and BTLA at various time points during the immune response.

Results

In rat models, combined therapy reduced the serum creatinine levels and prolonged graft survival compared to single therapy and control groups. Mixed acute rejection was shown in the allogeneic group and inhibited by combination treatment. Belatacept reduced the production of DSA and the deposition of C4d in grafts. Belatacept combined with BTLA overexpression downregulated the secretion of IL-2 and IFN-γ, as well as increasing IL-4 and IL-10 expression. We also found that Belatacept combined with BTLA overexpression inhibited the proliferation of spleen lymphocytes. The duration of the elevated expression levels of CTLA-4 and BTLA differentially affected the immune response.

Conclusion

Belatacept combined with BTLA overexpression attenuated acute rejection after kidney transplantation and prolonged kidney graft survival, which suggests a new approach for the optimization of early immunosuppression after kidney transplantation.
Multipotent Mesenchymal Stromal Cells in Rheumatoid Arthritis and Systemic Lupus Erythematosus; From a Leading Role in Pathogenesis to Potential Therapeutic Saviors?
Authors: El-Jawhari Jehan J. , El-Sherbiny Yasser , McGonagle Dennis , Jones Elena
Published: February 2021

The pathogenesis of the autoimmune rheumatological diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is complex with the involvement of several immune cell populations spanning both innate and adaptive immunity including different T-lymphocyte subsets and monocyte/macrophage lineage cells. Despite therapeutic advances in RA and SLE, some patients have persistent and stubbornly refractory disease. Herein, we discuss stromal cells' dual role, including multipotent mesenchymal stromal cells (MSCs) also used to be known as mesenchymal stem cells as potential protagonists in RA and SLE pathology and as potential therapeutic vehicles. Joint MSCs from different niches may exhibit prominent pro-inflammatory effects in experimental RA models directly contributing to cartilage damage. These stromal cells may also be key regulators of the immune system in SLE. Despite these pro-inflammatory roles, MSCs may be immunomodulatory and have potential therapeutic value to modulate immune responses favorably in these autoimmune conditions. In this review, the complex role and interactions between MSCs and the haematopoietically derived immune cells in RA and SLE are discussed. The harnessing of MSC immunomodulatory effects by contact-dependent and independent mechanisms, including MSC secretome and extracellular vesicles, is discussed in relation to RA and SLE considering the stromal immune microenvironment in the diseased joints. Data from translational studies employing MSC infusion therapy against inflammation in other settings are contextualized relative to the rheumatological setting. Although safety and proof of concept studies exist in RA and SLE supporting experimental and laboratory data, robust phase 3 clinical trial data in therapy-resistant RA and SLE is still lacking.
An Operational Numerical System for Oil Stranding Risk Assessment in a High-Density Vessel Traffic Area
Authors: Quattrocchi Giovanni , Simeone Simone , Pes Andrea , Sorgente Roberto , Ribotti Alberto , Cucco Andrea
Published: February 2021

In the Mediterranean Sea unique environmental characteristics and sensitive assets coexist with intense maritime traffic that is represented by frequent daily passages of vessels along the main waterways. In order to assess the risk of oil stranding in case of at-sea emergencies and provide key products for environmental agencies or policymakers preparedness, a geographically relocatable, operational numerical system is implemented and tested. The system relies on the application of oceanographic and particle tracking models and is able to provide, on a high-resolution and unstructured computational grid, a 3-days forecast of those variables known as the main drivers of oil slicks at sea. The risk of potential oil stranding is computed through a combination of anthropogenic hazard and shoreline vulnerability. The sources of hazard vary on time and space in relation to local maritime vessel traffic. The shoreline vulnerability is based on the current knowledge of slope, main grain size, geology of rocks, and occurrence of manmade structures at coast. The operational system is enriched by a web graphical user interface and includes automatic and on-demand working modes. Its functionality is demonstrated in the Strait of Bonifacio (western Mediterranean Sea), area with a high potential risk of oil stranding due to an intense maritime traffic. Risk assessment is hence computed for a test year, the 2018. Critical values of risk are found in correspondence of long stretches of littoral while many of them are currently characterized by a low anthropogenic pressure. The results emphasize the geomorphological features of the shorelines as reducing or amplifying factors to any potential impact of oil stranding at coast.
Neuropathic Itch: Routes to Clinical Diagnosis
Authors: Pereira Manuel Pedro , Wiegmann Henning , Agelopoulos Konstantin , Ständer Sonja
Published: February 2021

Neuropathic itch occurs due to damage of neurons of the peripheral or central nervous system. Several entities, including metabolic, neurodegenerative, orthopedic, infectious, autoimmune, malignant, and iatrogenic conditions, may affect the somatosensory system and induce neuropathic itch. Due to the complex nature of neuropathic itch, particularly concerning its clinical presentation and possible etiological factors, diagnostic work-up of this condition is challenging. A detailed medical history, especially in regard to the itch, and a comprehensive physical examination are relevant to detect characteristic signs and symptoms of neuropathic itch and to rule out other possible causes for chronic itch. Complementary diagnostic exams, especially laboratory tests, determination of the intraepidermal nerve fiber density via a skin biopsy and radiological examinations may be indicated to confirm the diagnosis of neuropathic itch and to identify underlying etiological factors. Functional assessments such as quantitative sensory testing, nerve conduction studies, evoked potentials, or microneurography may be considered in particular cases. This review article provides a comprehensive overview of the diagnostic work-up recommended for patients with neuropathic itch.
The Plasmid-Borne tet(A) Gene Is an Important Factor Causing Tigecycline Resistance in ST11 Carbapenem-Resistant Klebsiella pneumoniae Under Selective Pressure
Authors: Xu Juan , Zhu Zhongliang , Chen Yanmin , Wang Weizhong , He Fang
Published: February 2021

The emergence and prevalence of tigecycline-resistant Klebsiella pneumoniae have seriously compromised the effectiveness of antimicrobial agents in the treatment of infections. To explore the role of the plasmid-borne tet(A) gene in tigecycline resistance in carbapenem-resistant K. pneumoniae (CRKP), a total of 63 CRKP isolates were collected from a tertiary hospital in Hangzhou, China. The minimum inhibitory concentration (MIC) of tigecycline, mutation rate of tet(A) gene, genetic surroundings of tet(A)-carrying transmissible plasmid and the contribution of tet(A) mutation to tigecycline resistance were analyzed using antimicrobial susceptibility test, whole-genome sequencing, tigecycline resistance evolution experiment, and plasmid conjugation experiment. Our results showed that 52.4% (33 isolates) of the test isolates carried the tet(A) gene; among them, 75.8% (25 isolates) exhibited a tigecycline non-susceptible phenotype (MIC = 4 mg/L). Three clonal groups (cluster I, cluster II, and cluster III) were identified in these tet(A)-bearing isolates. All 17 isolates belonged to serotype KL21 (cluster I), which differed by only 13 SNPs, suggesting a clonal spread of tet(A)-positive ST11 K. pneumoniae with serotype KL21 occurred in the sampling hospital. The induction of tigecycline resistance experiments showed that 71.4% of strains evolved tet(A) mutations and developed a high-level tigecycline resistance. Eight amino acid substitutions were identified in these mutants. The most common amino acid substitution was A370V, followed by S251A and G300E. Twelve isolates carrying tet(A) mutants succeeded in the filter mating experiment with a conjugation efficiency of 10–3–10–8. Tigecycline MICs in E. coli EC600 transconjugants with a mutated tet(A) were 2 to 8-fold higher than those in E. coli EC600 transconjugants with a wild-type tet(A). One ColRNAI/IncFII type and two IncFII type tet(A)-bearing conjugative plasmids were identified in this study, including a class 1 integron containing multiple antibiotic resistance genes, i.e., tet(A), qnrS1, blaLAP–2, catA2, sul2, and dfrA14. Our study revealed the wide-spread situation of plasmid-borne tet(A) gene in clinical CRKP, and mutation of tet(A) is a potential driven force that lead to tigecycline resistance.
Large-Scale Morphological Network Efficiency of Human Brain: Cognitive Intelligence and Emotional Intelligence
Authors: Li Chunlin , Qiao Kaini , Mu Yan , Jiang Lili
Published: February 2021

Network efficiency characterizes how information flows within a network, and it has been used to study the neural basis of cognitive intelligence in adolescence, young adults, and elderly adults, in terms of the white matter in the human brain and functional connectivity networks. However, there were few studies investigating whether the human brain at different ages exhibited different underpins of cognitive and emotional intelligence (EI) from young adults to the middle-aged group, especially in terms of the morphological similarity networks in the human brain. In this study, we used 65 datasets (aging 18–64), including sMRI and behavioral measurements, to study the associations of network efficiency with cognitive intelligence and EI in young adults and the middle-aged group. We proposed a new method of defining the human brain morphological networks using the morphological distribution similarity (including cortical volume, surface area, and thickness). Our results showed inverted age × network efficiency interactions in the relationship of surface-area network efficiency with cognitive intelligence and EI: a negative age × global efficiency (nodal efficiency) interaction in cognitive intelligence, while a positive age × global efficiency (nodal efficiency) interaction in EI. In summary, this study not only proposed a new method of morphological similarity network but also emphasized the developmental effects on the brain mechanisms of intelligence from young adult to middle-aged groups and may promote mental health study on the middle-aged group in the future.
Differential Macrophage Responses in Affective Versus Non-Affective First-Episode Psychosis Patients
Authors: Hughes Heather K. , Mills-Ko Emily , Yang Houa , Lesh Tyler A. , Carter Cameron S. , Ashwood Paul
Published: February 2021

Increased innate immune activation and inflammation are common findings in psychotic and affective (mood) disorders such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD), including increased numbers and activation of monocytes and macrophages. These findings often differ depending on the disorder, for example, we previously found increases in circulating inflammatory cytokines associated with monocytes and macrophages in SCZ, while BD had increases in anti-inflammatory cytokines. Despite these differences, few studies have specifically compared immune dysfunction in affective versus non-affective psychotic disorders and none have compared functional monocyte responses across these disorders. To address this, we recruited 25 first episode psychosis (FEP) patients and 23 healthy controls (HC). FEP patients were further grouped based on the presence (AFF) or absence (NON) of mood disorder. We isolated peripheral blood mononuclear cells and cultured them for 1 week with M-CSF to obtain monocyte-derived macrophages. These cells were then stimulated for 24 h to skew them to inflammatory and alternative phenotypes, in order to identify differences in these responses. Following stimulation with LPS and LPS plus IFNγ, we found that macrophages from the NON-group had diminished inflammatory responses compared to both HC and AFF groups. Interestingly, when skewing macrophages to an alternative phenotype using LPS plus IL-4, the AFF macrophages increased production of inflammatory cytokines. Receiver operating curve analysis showed predictive power of inflammatory cytokine concentrations after LPS stimulation in the AFF group versus NON-group. Our results suggest dysfunctional monocyte responses in both affective and non-affective psychotic disorder, with varying types of immune dysfunction depending on the presence or absence of a mood component.
A Cost-Effectiveness Analysis of Systemic Therapy for Metastatic Hormone-Sensitive Prostate Cancer
Authors: Sung Winnie W. Y. , Choi Horace C. W. , Luk Peter H. Y. , So Tsz Him
Published: February 2021

Background

Currently, approved first-line treatment options of metastatic hormone-sensitive prostate cancer (mHSPC) include (1) androgen deprivation therapy (ADT) alone, ADT plus one of the following: (2) docetaxel, (3) abiraterone, (4) enzalutamide, and (5) apalutamide. The high cost of novel androgen receptor pathway inhibitors warrants an understanding of the combinations’ value by considering both efficacy and cost.

Objective

This study aimed to compare the cost-effectiveness of these five treatment options in mHSPC from the US payer perspective to guide treatment sequence.

Methods

A Markov model was developed to compare the lifetime cost and effectiveness of these five first-line treatment options for mHSPC using outcomes data from published literature. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Drug costs were obtained from the Veterans Affairs Pharmaceutical Catalog. We extrapolated survival beyond closure of the trials.

Outcome Measurements and Statistical Analysis

Life-years, QALYs, lifetime costs, and incremental cost-effectiveness ratios (ICERs) were estimated. Univariable, 2-way, and probabilistic sensitivity analyses were performed to evaluate parameter uncertainty. A willingness-to-pay (WTP) threshold of US$100,000 per QALY was used.

Results

Compared to ADT alone, docetaxel plus ADT provided a 0.28 QALY gain at an ICER of US$12,870 per QALY. Abiraterone plus ADT provided an additional 1.70 QALYs against docetaxel plus ADT, with an ICER of US$38,897 per QALY. Compared to abiraterone plus ADT, enzalutamide plus ADT provided an additional 0.87 QALYs at an ICER of US$509,813 per QALY. Apalutamide plus ADT was strongly dominated by enzalutamide plus ADT. Given the WTP threshold of US$100,000 per QALY, abiraterone plus ADT represented high-value health care.

Conclusions

Abiraterone plus ADT is the preferred treatment option for men with mHSPC at a WTP threshold of US$100,000 per QALY.
The Deubiquitinating Enzyme UCHL1 Induces Resistance to Doxorubicin in HER2+ Breast Cancer by Promoting Free Fatty Acid Synthesis
Authors: Lu Guangxian , Li Jianhua , Ding Leyun , Wang Chenping , Tang Lian , Liu Xin , Xu Jinhui , Zhou Qin , Sun Jiantong , Wang Wenjuan , Ding Xinyuan
Published: February 2021

Ubiquitin C-terminal hydrolase L1 (UCHL1), which is a deubiquitinating enzyme, is known to play a role in chemoresistance in cancers. However, its potential roles and mechanisms in the chemoresistance of breast cancer (BC) remain unclear. In this study, we examined its expression in patients with BC and employed Kaplan–Meier analysis and the log-rank test for survival analyses. It was found that up-regulated UCHL1 expression was positively associated with both chemoresistance and poor prognosis, especially in patients with HER2+ BC. Moreover, UCHL1 expression was elevated in HER2+ BC cells (SK-BR-3 and BT474). Similarly, doxorubicin (DOX)-resistant BC cells (MCF-7/DOX) had higher UCHL1 levels than MCF-7 cells. CCK-8 assay showed that BC cells with higher UCHL1 levels were more resistant to DOX. Furthermore, by inhibiting UCHL1 in BC cells with elevated UCHL1 expression, we demonstrated that UCHL1 promoted DOX-resistance in BC. Mechanistically, UCHL1 probably promoted DOX-resistance of BC by up-regulating free fatty acid (FFA) synthesis, as exhibited by reduced FFA synthase expression and resurrected DOX-sensitivity upon UCHL1 inhibition. Overall, UCHL1 up-regulation is associated with DOX-resistance and poor prognosis in patients with HER2+ BC. UCHL1 induces DOX-resistance by up-regulating FFA synthesis in HER2+ BC cells. Thus, UCHL1 might be a potential clinical target for overcoming DOX resistance in patients with HER2+ BC.
Sex-Based Heterogeneity in the Clinicopathological Characteristics and Prognosis of Breast Cancer: A Population-Based Analysis
Authors: Han Yiqun , Wang Jiayu , Wang Zijing , Xu Binghe
Published: February 2021

Purpose

To better understand the differences in clinicopathological features and prognosis between male breast cancer (MBC) and female breast cancer (FBC).

Material and Methods

Data on patients diagnosed with breast cancer from January 1, 2010, to December 31, 2016, were obtained from the Surveillance, Epidemiology, and End Results database. Selected patients were classified into MBC and FBC, of which population demographics and clinicopathological features at baseline were successively extracted for analysis. Comparative analysis was performed to explore the differences in baseline characteristics, followed by propensity-score matching to calibrate the objective distinctions for adjusted analysis. Survival analysis was carried out to investigate divergences presented in prognosis from the two cohorts, and risk factors for prognosis were successively identified using univariate and multivariate COX regression analyses.

Results

A total of 407341 individuals were eligible, including 3111 MBC (0.7%) and 404230 FBC (99.3%) patients. Comparatively, patients with MBC tended to be older at diagnosis, with a higher confirmation of ductal carcinoma, a higher histological grade, a higher TNM stage, a higher proportion of luminal-like subtype, a higher rate of lung metastasis, a lower incidence of liver involvement, and a lower rate of surgical, radiation, and chemotherapeutic delivery. The overall prognosis of MBC was significantly worse than that of FBC, with a decreasing divergence both in median overall survival (65.5 months vs. 72.7 months, P<0.0001) and median breast cancer-specific survival (75.4 months vs. 77.8 months, P<0.0001). However, these discrepancies were not consistent among patients from different subgroups stratified by molecular subtype, age at diagnosis, or disease stage.

Conclusion

In this study, sex-based heterogeneity in clinicopathological characteristics and prognostic profiles was observed in the overall population of patients with breast cancer and was significantly variable among different subgroups. A male-specific design with reasonable endpoints for a clinical trial protocol will be warranted in the future.
Construction of a SNP Fingerprinting Database and Population Genetic Analysis of Cigar Tobacco Germplasm Resources in China
Authors: Wang Yanyan , Lv Hongkun , Xiang Xiaohua , Yang Aiguo , Feng Quanfu , Dai Peigang , Li Yuan , Jiang Xun , Liu Guoxiang , Zhang Xingwei
Published: February 2021

Cigar tobacco is an important economic crop that is widely grown around the world. In recent years, varietal identification has become a frequent problem in germplasm preservation collections, which causes considerable inconvenience and uncertainty in the cataloging and preservation of cigar germplasm resources, in the selection of parental lines for breeding, and in the promotion and use of high quality varieties. Therefore, the use of DNA fingerprints to achieve rapid and accurate identification of varieties can play an important role in germplasm identification and property rights disputes. In this study, we used genotyping-by-sequencing (GBS) on 113 cigar tobacco accessions to develop SNP markers. After filtering, 580,942 high-quality SNPs were obtained. We used the 580,942 SNPs to perform principal component analysis (PCA), population structure analysis, and neighbor joining (NJ) cluster analysis on the 113 cigar tobacco accessions. The results showed that the accessions were not completely classified based on their geographical origins, and the genetic backgrounds of these cigar resources are complex and diverse. We further selected from these high-quality SNPs to obtained 163 SNP sites, 133 of which were successfully converted into KASP markers. Finally, 47 core KASP markers and 24 candidate core markers were developed. Using the core markers, we performed variety identification and fingerprinting in 216 cigar germplasm accessions. The results of SNP fingerprinting, 2D barcoding, and genetic analysis of cigar tobacco germplasm in this study provide a scientific basis for screening and identifying high-quality cigar tobacco germplasm, mining important genes, and broadening the basis of cigar tobacco genetics and subsequent breeding work at the molecular level.
On-Farm Trials Reveal Significant but Uncertain Control of Botrytis cinerea by Aureobasidium pullulans and Potassium Bicarbonate in Organic Grapevines
Authors: Laurent Anabelle , Makowski David , Aveline Nicolas , Dupin Séverine , Miguez Fernando E.
Published: February 2021

Botrytis cinerea, a fungal pathogen that causes gray mold on grapes, can decrease yield, substantially reduce wine quality, and therefore cause significant economic losses. In a context of increasing awareness of environmental and human health, biopesticides are a potential alternative to synthetic chemical treatments to produce grapes and wine in compliance with high food standards. However, the effectiveness of biopesticides is not well known and more research is needed to help winegrowers assess their ability to control wine diseases. Our study aims to assess the efficacy of two commercial biopesticides, based on potassium bicarbonate and Aureobasidium pullulans, in reducing the incidence of gray mold (i.e., the proportion of grape bunches that are diseased). We use data from an on-farm trial network managed over 3 years (from 2014 to 2016) in a major wine producing region located in Southwestern France, and fit Bayesian generalized linear multilevel models able to take the variability of treatment effect across trials into account. The fitted models were then used to estimate the efficacy on incidence as a function of the severity (i.e., the proportion of diseased grape berries in a bunch) in an untreated plot in order to determine if the effectiveness of the treatments depends on the disease pressure. At average disease severity (i.e., 3%), the efficacy on disease incidence at the network level was equal to 20% [95% CI = (−0.1; 37.3)] and 13% [95% CI = (0.2; 24.7)] for potassium bicarbonate and A. pullulans, respectively. For both biopesticides, the efficacy on incidence for a new site-year is highly uncertain, but potassium bicarbonate had a lower uncertainty and a lower application cost compared to A. pullulans. Our results confirm that potassium bicarbonate is an interesting biopesticide under farming conditions in organic vineyards in southwestern France, but the amount of uncertainty points to the need for further research.
Ascophyllum nodosum Extract (SealicitTM) Boosts Soybean Yield Through Reduction of Pod Shattering-Related Seed Loss and Enhanced Seed Production
Authors: Łangowski Łukasz , Goñi Oscar , Marques Fabio Serafim , Hamawaki Osvaldo Toshiyuki , da Silva Carolina Oliveira , Nogueira Ana Paula Oliveira , Teixeira Morgana Aparecida Justino , Glasenapp Jacqueline Siqueira , Pereira Marcio , O’Connell Shane
Published: February 2021

Soybean is one of the most valuable commercial crops because of its high protein, carbohydrate, and oil content. The land area cultivated with soybean in subtropical regions, such as Brazil, is continuously expanding, in some instances at the expense of carbon storing natural habitats. Strategies to decrease yield/seed losses and increase production efficiency are urgently required to meet global demand for soybean in a sustainable manner. Here, we evaluated the effectiveness of an Ascophyllum nodosum extract (ANE), SealicitTM, in increasing yields of different soybean varieties, in two geographical regions (Canada and Brazil). In addition, we investigated the potential of SealicitTM to reduce pod shattering at the trials in Brazil. Three different concentrations of SealicitTM were applied to pod shatter-susceptible (SS) UFUS 6901 and shatter-resistant (SR) UFUS 7415 varieties to assess their impact on pod firmness. SS variety demonstrated a significant decrease in pod shattering, which coincided with deregulation of GmPDH1.1 and GmSHAT1–5 expression, genes that determine pod dehiscence, and higher seed weight per pod. SealicitTM application to the SR variety did not significantly alter its inherent pod shatter resistance, but provided higher increases in seed yield at harvest. This yield increase maybe associated with to other yield components stimulated by the biostimulant. This work demonstrates that SealicitTM, which has previously been shown to improve pod firmness in Arabidopsis and selected commercial oilseed rape varieties through IND gene down-regulation, also has the potential to improve pod resistance and seed productivity in soybean, a member of the legume family sharing a similar strategy for seed dispersal.