bluuebunny/crossref_metadata_2025 huggingface dataset:
Test the quality of moisture content of corn seeds using a web-based capacitive method
Authors: Savero Ezhar
Published: June 2021

In an effort to control the quality of corn, among others, it is determined based on the moisture content in the corn seeds so that the corn produced has a seed quality standard. The purpose of this thesis is to determine the water level of the seeds. Corn was tested by a tool made with standardization of the moisture content of corn seeds from the Agricultural Center using the PM-650 Grain Moisture Tester. The parameters tested were the moisture content of the corn seeds, the temperature of the storage containers, and the weight of the corn seeds. Based on the research that has been done, it can be seen that a capacitive sensor with a working principle such as a parallel plate capacitor as a tool for measuring the moisture content of corn seeds has a reading accuracy ratio with the PM-650 Grain Moisture Tester measuring instrument is 94.9%. The temperature in the storage container was around 23 <temperature <27 to maintain the quality of the corn seeds. Data from the test results are sent via the ESP8266 module and displayed on the web. Based on the results of the planning and implementation that has been done, the capacitive sensor can work well as a measuring tool for the moisture content of corn seeds. Meanwhile, the difference in results in planning and measurement is caused by the losses that exist in the components used.
Design of System for Determining Corn Seed Color Quality Standards using the Fuzzy Logic Method through the Localhost Network
Authors: Alam Reksa Nirvana
Published: June 2021

Control of quality standards is very important role in ensuring corn on the market. Corn seed quality standards are determined from the results of  classification process applied. So far, evaluation process of classification of corn seeds quality is still done manually which takes a long time and the quality of product is'nt evenly distributed. So, we need a tool to determine corn seeds quality to improve its quality. This study conducted color readings of corn seeds using  TCS230 color sensors and sorting  diameter of corn seeds using a small, medium, and large diameter sieve machine. The method for classifying quality standard of corn seed color uses fuzzy logic. The test was carried out by taking data from 3 TCS230 color sensors on each diameter of the sieve machine for corn seeds types used are BISI-2 and BIMA-19. The sensor accuracy is known by comparing data from sensor with data from Color Grab application. The reading results of BISI-2 on the color sensor-1 shows an accuracy rate of 0.3%, the color sensor-2 shows an accuracy rate of 0.72%, and the color sensor-3 shows an accuracy rate of 1.76%. For BIMA-19 corn seeds, the reading on color sensor-1 shows an accuracy of 1.11%, the color sensor-2 shows an accuracy of 24.6%, the color sensor-3 shows an accuracy of 1.10%. The results of fuzzy testing on BISI-2 and BIMA-19 showed that quality standard of maize seeds was good at medium and large diameters, while those on small diameters showed poor quality standards.
Macrobending Loss Analysis on Singlemode-Multimode-Singlemode Fiber Optic Core
Authors: Andhina Sisca Arisya Harry
Published: June 2021

Macrobending often occurs in optical fibers that embedded in the ground due to shifting of soil or rocks in the ground causing interference in transmission. In this study used single-mode-multimode-singlemode fiber optic cable connected manually and axially measured using a light source test equipment and optical power meter and the results will be compared. The measurement results obtained the greater  value of macrobending losses with the smaller the diameter of the winding, and the greater the number of turns. The highest value of macrobending losses in multimode cables is -1.48dB at 0.5cm diameter with 5 turns, highest value of macrobending losses on single mode cables is -12.73dB at 0.5cm diameter with 5 turns,  lowest value of macrobending losses for multimode cables is -0.44dB at 5cm diameter with 1 twist, lowest macrobending losses in singlemode cables is -1.69dB at 5cm diameter with 1 twist. While the value of macrobending losses on axially connected SMS cables shows the highest value of macrobending losses on multimode cables is -1.12dB in diameter of 0.5cm with 5 turns,  highest value of macrobending losses on singlemode cables is -1.18dB at diameter of 0.5cm with 5 turns,  lowest value for macrobending losses on multimode cables is -0.66dB at 5cm in diameter with 1 twist, the smallest value for macrobending losses on singlemode cables is -0.27dB at 5cm diameter with 1 twist . The measurement results also showed that the macrobending losses of manually connected SMS cables were greater than the macrobending losses of axially connected SMS cables.
Analysis of 4G Network Performance in Malang Region
Authors: Suroyya Nidya
Published: June 2021

The implementation of LTE in Indonesia has experienced problems, especially in maintaining the performance of radio networks due to the increasing number of users and less than optimal coverage quality. This research will conduct an analysis of the performance of the 4G LTE network with a case study in the area around Jalan Jend. Basuki Rachmat and Malang City Station. The Key Performance Indicator (KPI) parameters used to measure the performance of the 4G LTE network in this study include RRC setup success rate, ERAB setup success rate, and Call setup success rate Accessibility, call drop rate (VoiP), service drop rate (all). Retainability, handover, Throughput and Radio Frequency (RF), data obtained from drive tests and statistical data.From the standard KPI data for the Drive test area, Jend.basuki Rachmat has a value above -100 dBm, the percentage of power transmitted is 100% with a download value of 98.83% throughput of more than 265 Mbps and an upload value of 100% throughputI of more than 265 Mbps. As well as the Malang City Station area has a value above -100 dBm, the percentage of transmitted power is 92.39% with a download value of 96.12% throughput of more than 265 Mbps and an upload value of 100% throughputI of more than 265 Mbps. The parameters of Accessibility, Retainability, Mobility, integrity and Radio Frequency (RF) must comply with KPI standards in order to get maximum performance according to user needs.
Implementation of Voice Transmission Through Optical Fiber using different LEDs
Authors: Hafidhotunnisa Ummi
Published: June 2021

Optical fiber is a transmission medium for sending information that uses light as a source of information. Optical fiber can be used as a transmission medium to transmit information in the form of data, video and voice. Of the various kinds of light sources used, the most bpouler used is laser. Even though there are still many light sources used, namely leds. In this research, the design of a sound transmission transmission system is designed, but by using a led light source with different colors. With different colors means the wavelength of the led is also different. This affects the amount of information conveyed at the receiving end. The results showed unsatisfactory results, due to the limited standard of existing components and the angle of light reception that did not meet the standards from the optical fiber reception angle. However, there are several results from the study, namely the value of reinforcement from the sender's side has a difference of 2.4. In the measurement of the SNR value, the SNR value of the LED is greater than the SNR value of the laser when without using a cable of 0.1387 and when using a measuring cable of 3.5924 x 10-5. Then also generated a reinforcement response to changes in the frequency value. The greater the frequency value, the lower the gain.
Design and Build a Digital Loyal Customer Card System for an RFID-Based Moshi-Moshi Ramen Restaurant
Authors: Haitami Muhammad Whildan
Published: June 2021

Loyal customers at a restaurant definitely want a reward for their loyalty to the restaurant, Moshi-Moshi Ramen created the Loyal Customers program as an appreciation for loyal customers. The program is made using a paper card with 10 empty boxes which is stamped by the cashier when the customer pays for food. The current era of globalization allows all areas of life to be assisted by the presence of technology. One of the technologies developed in the culinary field is the design of a digital loyal customer card system based on Radio Frequency Identifier (RFID) which has been linked to the Firebase web database as a medium for storing data. It was found that there were deficiencies in the loyalty program, namely the card that was not safe to hold, especially if the card was lost, the customer could not claim the number of stamps So, to solve this problem, RFID and pin numbers are used as a safer system of loyal customer cards and the database for storing registered customer data to transform the existing loyalty customer program into a smarter system. Making a digital loyal customer card system using an RFID tag can be done using the Arduino Uno R3 microcontroller which has a reading sensitivity of up to a distance of 4.5 cm and an android application for ordering food. As well as all functions that can run well, including comparison of transaction times using manual and digital systems with a time difference of 10 seconds.
Strategic overview of digital public participation tools for urban planning
Authors: Estafam Ali
Published: June 2021

In light of the current pandemic, and the subsequent social distancing measures it imposed, this research aims to contribute to the literature of digital public participation methods for urban planning. It will specifically investigate the correlation between the technical knowledge required by digital public participation tools and levels of engagement, and the consequences of digital public participation to underserved populations. The requirements for digital knowledge and the levels of engagement will be used as axes of a matrix, in which the digital engagement tools will be plotted. The comparison of these variables will lead to the conclusion that the higher is the level of engagement, the higher is the requirement of digital knowledge, and therefore, the less accessible the method is for underserved communities. The research will finalize with some suggestions on how to overcome these challenges, which include the mitigation of digital literacy gaps through education, and the use of the current tools in more creative ways, prioritizing the low-tech ones, to enhance inclusivity and equity to urban planning projects and plans.
Artemisia argyi Essential Oil Inhibits Hepatocellular Carcinoma Metastasis via Suppression of DEPDC1 Dependent Wnt/β-Catenin Signaling Pathway
Authors: Li Yanli , Tian Yang , Zhong Wei , Wang Ning , Wang Yafeng , Zhang Yan , Zhang Zhuangli , Li Jianbo , Ma Fang , Zhao Zhihong , Peng Youmei
Published: June 2021

The tumor metastasis is the major hurdle for the treatment of advanced hepatocellular carcinoma (HCC), due in part to the lack of effective systemic treatments. DEPDC1, a novel oncoantigen upregulated in HCC, is thought to be a molecular-target for novel therapeutic drugs. Artemisia argyi is a traditional Chinese medicine with anti-inflammatory and anti-tumor activities. This study investigated the potential therapeutic benefits of Artemisia argyi essential oil (AAEO) in suppressing metastasis of HCC by targeting DEPDC1. Assessment of AAEO cytotoxicity was performed by MTT assay. Anti-metastatic effects of AAEO were investigated in vitro using wound healing and transwell assays. The HepG2 cells were transduced with lentiviral vector containing luciferase (Luc). A metastasis model of nude mice was established by tail vein injection of HepG2-Luc cells. The nude mice were treated with AAEO (57.5, 115, and 230 mg/kg) or sorafenib (40 mg/kg). Metastasis of HCC cells was monitored via in vivo bioluminescence imaging. After treatment for 21 days, tissues were collected for histological examination and immunohistochemistry analysis. Gene and protein levels were determined by real-time quantitative PCR and western blotting. The results revealed that AAEO significantly inhibits the migration and invasion in vitro in a concentration-dependent manner. In vivo assays further confirmed that AAEO markedly inhibits HCC metastasis into lung, brain, and femur tissues and exhibits low toxicity. Our results suggested that AAEO significantly downregulates the mRNA and protein expression of DEPDC1. Also, AAEO attenuated Wnt/β-catenin signaling through reduction of Wnt1 and β-catenin production. Moreover, AAEO prevented epithelial-mesenchymal transition (EMT) by downregulation of vimentin and upregulation of E-cadherin. Furthermore, we found that DEPDC1 promoted HCC migration and invasion via Wnt/β-catenin signaling pathway and EMT. These results demonstrate that AAEO effectively inhibits HCC metastasis via attenuating Wnt/β-catenin signaling and inhibiting EMT by suppressing DEPDC1 expression. Thus, AAEO likely acts as a novel inhibitor of the DEPDC1 dependent Wnt/β-catenin signaling pathway.
Assessing the Concordance Between Urogenital and Vaginal Microbiota: Can Urine Specimens Be Used as a Proxy for Vaginal Samples?
Authors: Brown Sarah E. , Robinson Courtney K. , Shardell Michelle D. , Holm Johanna B. , Ravel Jacques , Ghanem Khalil G. , Brotman Rebecca M.
Published: June 2021

Background

The vaginal microbiota play a key role in defense against reproductive tract infections; however, many population-based women’s health studies do not collect vaginal samples. Molecular examinations of urine samples have revealed common vaginal bacteria. We sought to assess the extent that community state type assignments of archived random-catch and clean-catch urine samples agreed with the paired vaginal samples in both reproductive-age and peri/post-menopausal women.

Results

Using archived samples, we evaluated the microbiota concordance among women in three studies: two with paired mid-vaginal/random-catch urine (N=91 reproductive-age participants and N=13 peri/post-menopausal participants), and one with paired mid-vaginal/clean-catch urine (N=99 reproductive-age participants). Microbiota composition was characterized by sequencing amplicons of the 16S rRNA gene V3-V4 regions and assigned to community state types. Similarity of paired samples was gauged using agreement of community state types and Yue-Clayton θ indices. Analysis of Composition of Microbiomes II indicated which taxa were differently relatively abundant in paired vaginal and urine samples. In reproductive-age women, random-catch and clean-catch urines were 89.0% and 86.9% concordant on five community state types with paired mid-vaginal swabs, and Kappa statistics indicated almost perfect agreement (κrandom-catch=.85, κclean-catch=.81, p<0.0001). A small number of pairs of samples were discordant (23/190, 12%), and discordant pairs tended to be between samples classified to L. iners-dominated and/or low-Lactobacillus states. Concordance and agreement remained similar when dichotomizing the microbiota to Lactobacillus-dominated versus low-Lactobacillus microbiota, as well as when evaluating separately the three subtypes of the low-Lactobacillus community state type IV. Median similarity of paired urine/vaginal samples was high (θrandom-catch=.85, θclean-catch=.88), and a comparison of the random-catch and clean-catch similarity scores showed no significant difference (p=.80). Concordance and similarity were lower for peri/post-menopausal women, but agreement remained substantial (76.9% concordant, κrandom-catch= 0.64, θrandom-catch=.62). Taxonomic-level analysis confirmed these findings.

Conclusions

Random-catch and clean-catch urine samples showed substantial agreement on bacterial composition to paired mid-vaginal samples, indicating that the genitourinary microbiota may be a reliable proxy for assessing the overall composition of the vaginal microbiota via community state types. This data suggests that urine samples can, with proper interpretation, be utilized as a surrogate for developing preliminary data and hypothesis-generating studies.
A Simulation Design of Immersive Virtual Reality for Animal Handling Training to Biomedical Sciences Undergraduates
Authors: Tang Florence Mei Kuen , Lee Ray Mau Fung , Szeto Roy Hok Lai , Cheng Jason Ka Kit , Choi Frederic Wai To , Cheung Justin Chak Ting , Ngan Olivia Miu Yung , Lau Ann Sin Nga
Published: June 2021

Background: One area of biomedical research concerns is applying new treatments to cure human diseases, moving bench-side research to the bedside practice. While using animal models is crucial in the research process, researchers should strictly adhere to the moral 4R framework to protect animal welfare—replacement, reduction, refinement, and responsibility. Virtual reality (VR) applies computer technology to create a simulated environment, allowing players to immerse and interact with animated 3D contexts. We developed a virtual animal-holding simulator (ViSi) using immersive virtual reality technology for students studying in the undergraduate biomedical sciences programme. The specific objectives of the paper are to 1) describe the development of the VR courseware for animal training and 2) describe the learning experience among students.

Method and Result: An evaluation of the courseware was conducted among Year one and two biomedical sciences students. Students who participated in ViSi responded positively about their involvement in the virtual environment experience and their concentration on the assigned task.

Discussion: ViSi is a reliable simulation technology that can train animal handling skills, which replaces real animals, while learners’ multi-cognition could still be enhanced with simulation training. Thus, the impact of immersive VR technology integrated into skills training is promising, although few technical problems are to be resolved.
Identifying miRNA-mRNA Integration Set Associated With Survival Time
Authors: Kim Yongkang , Lee Sungyoung , Jang Jin-Young , Lee Seungyeoun , Park Taesung
Published: June 2021

In the “personalized medicine” era, one of the most difficult problems is identification of combined markers from different omics platforms. Many methods have been developed to identify candidate markers for each type of omics data, but few methods facilitate the identification of multiple markers on multi-omics platforms. microRNAs (miRNAs) is well known to affect only indirectly phenotypes by regulating mRNA expression and/or protein translation. To take into account this knowledge into practice, we suggest a miRNA-mRNA integration model for survival time analysis, calledmimi-surv, which accounts for the biological relationship, to identify such integrated markers more efficiently. Through simulation studies, we found that the statistical power ofmimi-survbe better than other models. Application to real datasets from Seoul National University Hospital and The Cancer Genome Atlas demonstrated thatmimi-survsuccessfully identified miRNA-mRNA integrations sets associated with progression-free survival of pancreatic ductal adenocarcinoma (PDAC) patients. Onlymimi-survfound miR-96, a previously unidentified PDAC-related miRNA in these two real datasets. Furthermore,mimi-survwas shown to identify more PDAC related miRNAs than other methods because it used the known structure for miRNA-mRNA regularization. An implementation ofmimi-survis available athttp://statgen.snu.ac.kr/software/mimi-surv.
Globus Pallidus Internus Deep Brain Stimulation Using Frame-Based vs. Frameless Stereotaxy in Dystonia: A Single-Center Experience
Authors: Eleopra Roberto , Rinaldo Sara , Devigili Grazia , Mondani Massimo , D'Auria Stanislao , Golfrè Andreasi Nico , Skrap Miran , Lettieri Christian
Published: June 2021

Objective: Bilateral globus pallidus internus deep brain stimulation (GPi-DBS) is an established and effective therapy for primary refractory dystonia. However, the comparison of frameless vs. frame-based DBS surgery technique is still controversial. This retrospective study aims to compare the clinical outcome of two GPi-DBS surgical techniques for patients affected by primary generalized or multi-segmental dystonia.

Methods: For lead's stereotaxic placement, 10 patients underwent frame-based surgery and the other 10 subjects DBS surgery with a frameless technique. Clinical features were evaluated at baseline and 6 and 12 months after surgery by means of the Burke–Fahn–Marsden Dystonia Rating Scale.

Results: Frame-based GPi-DBS and frameless stereotaxic group revealed a comparable clinical outcome with no surgical complications.

Conclusions: Frameless technique is safe and well-tolerated by patients and showed similar effectiveness of the frame-based stereotaxic surgery during GPi-DBS for primary dystonia. Notably, it could be a valid alternative solution because of the great advantage in improving the patient's discomfort during awake surgery.
Action Video Gaming Experience Related to Altered Resting-State EEG Temporal and Spatial Complexity
Authors: Cui Ruifang , Jiang Jinliang , Zeng Lu , Jiang Lijun , Xia Zeling , Dong Li , Gong Diankun , Yan Guojian , Ma Weiyi , Yao Dezhong
Published: June 2021

Action video gaming (AVG) places sustained cognitive load on various behavioral systems, thus offering new insights into learning-related neural plasticity. This study aims to determine whether AVG experience is associated with resting-state electroencephalogram (rs-EEG) temporal and spatial complexity, and if so, whether this effect is observable across AVG subgenres. Two AVG games – League of Legends (LOL) and Player Unknown’s Battle Grounds (PUBG) that represent two major AVG subgenres – were examined. We compared rs-EEG microstate and omega complexity between LOL experts and non-experts (Experiment 1) and between PUBG experts and non-experts (Experiment 2). We found that the experts and non-experts had different rs-EEG activities in both experiments, thus revealing the adaptive effect of AVG experience on brain development. Furthermore, we also found certain subgenre-specific complexity changes, supporting the recent proposal that AVG should be categorized based on the gaming mechanics of a specific game rather than a generic genre designation.
Influence of Different Types of Drying Methods on Color Properties, Phenolic Metabolites and Bioactivities of Pumpkin Leaves of var. Butternut squash (Cucurbita moschata Duchesne ex Poir)
Authors: Mashitoa Florence M. , Shoko Tinotenda , Shai Jerry L. , Slabbert Retha M. , Sultanbawa Yasmina , Sivakumar Dharini
Published: June 2021

Leaves of pumpkin species var. Butternut squash (Cucurbita moschata Duchesne ex Poir) is a popularly consumed leafy vegetable in the Southern African region. Traditional vegetables are commonly sun-dried as a method of postharvest preservation during the off-season. However, different drying methods affect the superior quality, functional properties, and bioactivities of the final product. Therefore, in this study, var. Butternut squash (C. moschata) underwent different drying methods, such as freeze-, oven, sun-, solar, and microwave drying to evaluate the color properties, pigments, phenolic metabolites, in vitro antioxidants, and antidiabetic activities. Results indicate that freeze-drying retained the total chlorophyll content with green color by reducing the color difference (ΔE), improved the concentration of different phenolic metabolites and the content of ascorbic acid, and enhanced the FRAP, ABTS activities and the inhibitory effects of α-glucosidase, and α-amylase. Freeze-dried leaves contained the highest concentrations of quercetin 3-glucoside 7-rhamnoside (rutin), quercetin 3-galactoside, isorhamnetin-3-galactoside-6″-rhamnoside, isorhamnetin-3-O-rutinoside compared with the leaves that underwent four other drying treatments and raw leaves. The OPLS-DA and the UPLC–QTOF/MS and chemometric approach showed that the peak at m/z 609, 1441 (quercetin 3-galactoside 7-rhamnoside) separated the freeze-dried leaves of var. Butternut squash (C. moschata) from the other four drying treatments. Therefore, freeze-drying is highly recommended to obtain good quality leaf powders that are rich in functional compounds and bioactive properties for use as functional ingredients.
First-Line Chemo-Immunotherapy for Extensive-Stage Small-Cell Lung Cancer: A United States-Based Cost-Effectiveness Analysis
Authors: Liu Qiao , Luo Xia , Yi Lidan , Zeng Xiaohui , Tan Chongqing
Published: June 2021

Objective

This study aimed to assess the cost-effectiveness of two recently approved first-line chemo-immunotherapies [atezolizumab combined with etoposide and platinum (AEP) and durvalumab combined with etoposide and platinum (DEP)] for patients with extensive-stage small-cell lung cancer (ES-SCLC) in the United States.

Material and Methods

A Markov model was built to compare the cost and effectiveness of AEP, DEP, and etoposide plus platinum (EP) over a 10-year time horizon. Clinical efficacy and safety data were extracted from the IMpower 133 and CASPIAN trials. Health state utilities were obtained from published literature. Costs were collected from an US payer perspective. Deterministic and probabilistic sensitivity analyses were used to explore the uncertainty bound to model parameters.

Results

For the model cohort of adult patients with treatment-naive ES-SCLC, AEP was associated with marginal improved quality adjusted life years (QALYs) by 0.016 and reduced costs by $5,737 compared with DEP. When comparing the two chemo-immunotherapies with EP chemotherapy, AEP and DEP increased the QALYs by 0.162 QALYs and 0.146, respectively. However, both chemo-immunotherapies were associated with substantially health costs than EP, resulting in ICERs of $382,469 per QALY and $464,593 per QALY, respectively.

Conclusion

In this cost-effectiveness study, first-line AEP represented a dominant treatment strategy compared with DEP. Despite neither first-line AEP nor first-line DEP was cost-effective compared with EP chemotherapy, AEP was able to provide a more efficient balance between incremental cost and QALY than DEP. When new combination therapies with remarkable effect become pivotal in the first-line treatment, the price reduction of these drugs may be essential to achieving cost-effectiveness.
Therapeutic and Prognostic Implications of Immune-Related Adverse Events in Advanced Non-Small-Cell Lung Cancer
Authors: Daniello Lea , Elshiaty Mariam , Bozorgmehr Farastuk , Kuon Jonas , Kazdal Daniel , Schindler Hannah , Shah Rajiv , Volckmar Anna-Lena , Lusky Fabienne , Diekmann Leonore , Liersch Stephan , Faehling Martin , Muley Thomas , Kriegsmann Mark , Benesova Karolina , Stenzinger Albrecht , Thomas Michael , Christopoulos Petros
Published: June 2021

Introduction

PD-(L)1 inhibitors have improved prognosis of non-small-cell lung cancer (NSCLC), but can also cause immune-related adverse events (irAEs) that complicate management.

Methods

We analyzed NSCLC patients receiving PD-(L)1 inhibitors from 2012 to 2020 in a German academic center.

Results

IrAE showed comparable frequencies in stage IV (198/894 or 22%) vs. III (14/45 or 31%, p = 0.15), after anti-PD-(L)1 monotherapy vs. chemoimmunotherapy (139/483 vs. 58/213, p = 0.75), and across treatment lines. In stage IV, irAE occurred after 3.1 months in median, affected multiple organs (median 2) in 27/894 patients and were associated with PD-L1 positivity (25 vs. 14%, p = 0.003), lower neutrophil-to-lymphocyte ratios (29 vs. 17%, p < 0.001 for NLR dichotomized at 5), better ECOG status (26 vs. 18% for 0 vs. 1, p = 0.004), but not related to age, sex, smoking and palliative radiotherapy. Two hundred thirty two irAEs occurred mostly in endocrine glands (4.9%), lungs (4.4%), the musculoskeletal system (4.2%), colon (4.1%), liver (3.7%), and skin (2.6%), while pneumonitis was most frequent with durvalumab following definitive chemoradiation (16% or 7/45, p < 0.01). IrAE severity was grade 1 in 11%, 2 in 41%, 3 in 36%, and 4 in 11% events, while two were lethal (<1%, myocarditis and pneumonitis). Therapy was suspended in 72%, while steroids were initiated in 66% and complemented by other immunosuppressants in 6%, with longest treatment duration for rheumatic events (mean >3 months), and average cumulative prednisone doses >700 mg for all organs, except for skin. Patients developing irAE had longer progression-free (PFS) and overall survival (OS) in multivariable 12/14-week landmark analyses including ECOG status, treatment line, treatment type, PD-L1 TPS, and NLR (median PFS 17 vs. 10 months, HR = 0.68, p = 0.009; median OS 37 vs. 15 months, HR = 0.40, p < 0.001), regardless of grade. OS was longest with skin (95% at 2 years) and shortest with pneumonitis, hepatitis, neurologic, and cardiologic irAE (38, 37, 28, and 0% at 2 years, p < 0.001).

Conclusions

Approximately one-fourth of immunotherapy-treated NSCLC patients develop irAEs, most of which necessitate treatment suspension and steroids. Despite more frequent occurrence with PD-L1 positive tumors, lower NLR, and better ECOG PS, irAEs are independently associated with longer survival, especially when affecting the skin. Lethality is below 1%.
Fitness Cost Associated With Enhanced EPSPS Gene Copy Number and Glyphosate Resistance in an Amaranthus tuberculatus Population
Authors: Cockerton Helen M. , Kaundun Shiv S. , Nguyen Lieselot , Hutchings Sarah Jane , Dale Richard P. , Howell Anushka , Neve Paul
Published: June 2021

The evolution of resistance to pesticides in agricultural systems provides an opportunity to study the fitness costs and benefits of novel adaptive traits. Here, we studied a population of Amaranthus tuberculatus (common waterhemp), which has evolved resistance to glyphosate. The growth and fitness of seed families with contrasting levels of glyphosate resistance was assessed in the absence of glyphosate to determine their ability to compete for resources under intra- and interspecific competition. We identified a positive correlation between the level of glyphosate resistance and gene copy number for the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) glyphosate target, thus identifying gene amplification as the mechanism of resistance within the population. Resistant A. tuberculatus plants were found to have a lower competitive response when compared to the susceptible phenotypes with 2.76 glyphosate resistant plants being required to have an equal competitive effect as a single susceptible plant. A growth trade-off was associated with the gene amplification mechanism under intra-phenotypic competition where 20 extra gene copies were associated with a 26.5 % reduction in dry biomass. Interestingly, this growth trade-off was mitigated when assessed under interspecific competition from maize.
Comparative Performance of High-Yielding European Wheat Cultivars Under Contrasting Mediterranean Conditions
Authors: de Lima Valter Jário , Gracia-Romero Adrian , Rezzouk Fatima Zahra , Diez-Fraile Maria Carmen , Araus-Gonzalez Ismael , Kamphorst Samuel Henrique , do Amaral Júnior Antonio Teixeira , Kefauver Shawn C. , Aparicio Nieves , Araus Jose Luis
Published: June 2021

Understanding the interaction between genotype performance and the target environment is the key to improving genetic gain, particularly in the context of climate change. Wheat production is seriously compromised in agricultural regions affected by water and heat stress, such as the Mediterranean basin. Moreover, wheat production may be also limited by the nitrogen availability in the soil. We have sought to dissect the agronomic and physiological traits related to the performance of 12 high-yield European bread wheat varieties under Mediterranean rainfed conditions and different levels of N fertilization during two contrasting crop seasons. Grain yield was more than two times higher in the first season than the second season and was associated with much greater rainfall and lower temperatures. However, the nitrogen effect was rather minor. Genotypic effects existed for the two seasons. While several of the varieties from central/northern Europe yielded more than those from southern Europe during the optimal season, the opposite trend occurred in the dry season. The varieties from central/northern Europe were associated with delayed phenology and a longer crop cycle, while the varieties from southern Europe were characterized by a shorter crop cycle but comparatively higher duration of the reproductive period, associated with an earlier beginning of stem elongation and a greater number of ears per area. However, some of the cultivars from northern Europe maintained a relatively high yield capacity in both seasons. Thus, KWS Siskin from the UK exhibited intermediate phenology, resulting in a relatively long reproductive period, together with a high green area throughout the crop cycle.
Effects of Melatonin on Morphological Characteristics, Mineral Nutrition, Nitrogen Metabolism, and Energy Status in Alfalfa Under High-Nitrate Stress
Authors: Chen Zhao , Cao Xinlong , Niu Junpeng
Published: June 2021

Melatonin is an indoleamine small molecular substance that has been shown to play an important role in the growth, development, and stress response of plants. The effects of melatonin on the morphological characteristics, mineral nutrition, nitrogen metabolism, and energy status in alfalfa (Medicago sativa L.) under high-nitrate stress were studied. The alfalfa plants were treated with water (CK), 200 mmol L−1 nitrates (HN), or 200 mmol L−1 nitrates + 0.1 mmol L−1 melatonin (HN+MT), and then were sampled for measurements on days 0 and 10, respectively. The results showed that the HN treatment resulted in a decrease in the morphological characteristics (such as shoot height, leaf length, leaf width, leaf area, and biomass), phosphorus, soluble protein (SP), nitrogen-related enzymes activities and gene relative expression, adenosine triphosphate (ATP), and energy charge (EC). It also caused an increase in nitrogen, sodium, potassium, calcium, nitrate-nitrogen (NO3--N), ammonium-nitrogen (NH4+-N), adenosine diphosphate (ADP), and adenosine monophosphate (AMP). However, these parameters were conversely changed in the HN+MT treatment. Besides, these parameters were closely related to each other, and were divided into two principal components. It reveals that melatonin plays an important role in modulating the morphology, mineral nutrition, nitrogen metabolism and energy status, thereby alleviating the adverse effects of high-nitrate stress and improving the growth of alfalfa.
The Different Faces of Insomnia
Authors: Fietze Ingo , Laharnar Naima , Koellner Volker , Penzel Thomas
Published: June 2021

Objectives: The identification of clinically relevant subtypes of insomnia is important. Including a comprehensive literature review, this study also introduces new phenotypical relevant parameters by describing a specific insomnia cohort.

Methods: Patients visiting the sleep center and indicating self-reported signs of insomnia were examined by a sleep specialist who confirmed an insomnia diagnosis. A 14-item insomnia questionnaire on symptoms, progression, sleep history and treatment, was part of the clinical routine.

Results: A cohort of 456 insomnia patients was described (56% women, mean age 52 ± 16 years). They had suffered from symptoms for about 12 ± 11 years before seeing a sleep specialist. About 40–50% mentioned a trigger (most frequently psychological triggers), a history of being bad sleepers to begin with, a family history of sleep problems, and a negative progression of insomnia. Over one third were not able to fall asleep during the day. SMI (sleep maintenance insomnia) symptoms were most frequent, but only prevalence of EMA (early morning awakening) symptoms significantly increased from 40 to 45% over time. Alternative non-medical treatments were effective in fewer than 10% of cases.

Conclusion: Our specific cohort displayed a long history of suffering and the sleep specialist is usually not the first point of contact. We aimed to describe specific characteristics of insomnia with a simple questionnaire, containing questions (e.g., ability to fall asleep during the day, effects of non-medical therapy methods, symptom stability) not yet commonly asked and of unknown clinical relevance as yet. We suggest adding them to anamnesis to help differentiate the severity of insomnia and initiate further research, leading to a better understanding of the severity of insomnia and individualized therapy. This study is part of a specific Research Topic introduced by Frontiers on the heterogeneity of insomnia and its comorbidity and will hopefully inspire more research in this area.
Data-Driven Tuning of PID Controlled Piezoelectric Ultrasonic Motor
Authors: Makarem Sarah , Delibas Bülent , Koc Burhanettin
Published: June 2021

Ultrasonic motors employ resonance to amplify the vibrations of piezoelectric actuator, offering precise positioning and relatively long travel distances and making them ideal for robotic, optical, metrology and medical applications. As operating in resonance and force transfer through friction lead to nonlinear characteristics like creep and hysteresis, it is difficult to apply model-based control, so data-driven control offers a good alternative. Data-driven techniques are used here for iterative feedback tuning of a proportional integral derivative (PID) controller parameters and comparing between different motor driving techniques, single source and dual source dual frequency (DSDF). The controller and stage system used are both produced by the company Physik Instrumente GmbH, where a PID controller is tuned with the help of four search methods: grid search, Luus–Jaakola method, genetic algorithm, and a new hybrid method developed that combines elements of grid search and Luus–Jaakola method. The latter method was found to be quick to converge and produced consistent result, similar to the Luus–Jaakola method. Genetic Algorithm was much slower and produced sub optimal results. The grid search has also proven the DSDF driving method to be robust, less parameter dependent, and produces far less integral position error than the single source driving method.
\({\mathcal{L}_1}\) Adaptive Loss Fault Tolerance Control of Unmanned Hypersonic Aircraft with Elasticity
Authors: Li Zhaoying , Shi Shuai
Published: June 2021

This paper investigates the fault tolerance control of hypersonic aircrafts with L1 adaptive control method in the presence of loss of actuator effectiveness fault. The hypersonic model considers the uncertainties caused by the features of nonlinearities and couplings. Elasticity is taken into account in hypersonic vehicle modeling which makes the model more accurate. A velocity L1 adaptive controller and an altitude L1 adaptive controller are designed to control flexible hypersonic vehicle model with actuator loss fault. A PID controller is designed as well for comparison. Finally, the simulation results are used to analyze the effectiveness of the controller. Compared to the results of PID controller, L1 controllers have better performance.
Advantages of Amending Chemical Fertilizer with Plant-Growth-Promoting Rhizobacteria under Alternate Wetting Drying Rice Cultivation
Authors: Kobua Chesly Kit , Jou Ying-Tzy , Wang Yu-Min
Published: June 2021

Chemical fertilizer (CF) is necessary for optimal growth and grain production in rice farming. However, the continuous application of synthetic substances has adverse effects on the natural environment. Amending synthetic fertilizer with plant-growth-promoting rhizobacteria (PGPR) is an alternate option to reduce CF usage. In this study, a field trial was undertaken in southern Taiwan. We aimed to investigate the effects of reducing CF, either partially or completely, with PGPR on the vegetative growth, biomass production, and grain yield of rice plants cultivated under alternate wetting and drying (AWD) cultivation. In addition, we aimed to determine an optimal reduction in CF dose when incorporated with PGPR for application in rice cultivation under AWD. The trial consisted of four treatments, namely, 0% CF + 100% PGPR (FP1), 25% CF + 75% PGPR (FP2) 50% CF + 50% PGPR (FP3), and 100% CF + 0% PGPR (CONT). A randomized complete blocked design (RCBD) with three replicates was used. A reduction in CF by 25–50% with the difference compensated by PGPR significantly (p ≤ 0.05) influenced the crops biomass production. This improved the percentage of filled grains (PFG), and the thousand-grain weight (1000-GW) of treated plants by 4–5%. These improvements in growth and yield components eventually increased the grain yield production by 14%. It is concluded that partial replacement of CF with PGPR could be a viable approach to reduce the use of CF in existing rice cultivation systems. Furthermore, the approach has potential as a sustainable technique for rice cultivation.
One-Time Acidification of Slurry: What Is the Most Effective Acid and Treatment Strategy?
Authors: Overmeyer Veronika , Kube Anita , Clemens Joachim , Büscher Wolfgang , Trimborn Manfred
Published: June 2021

Acidification of slurry is a common practice to reduce ammonia and methane emissions. Sulfuric acid is usually used for this process. However, this has been criticized due to the high sulfur input into soils. Therefore, the objective of this study is to show the effectiveness of a one-time acidification with alternative acids also in combination with other treatment strategies. The amount of acid as well as the change of pH value during storage were investigated. For most variants, a strong pH increase occurred within the first ten days after acidification. Mineral acids (sulfuric or hydrochloric acid) resulted in a lower pH increase compared to organic acids (lactic, acetic, and citric acid). Under anaerobic storage conditions, the pH remained significantly lower. The addition of glucose before acidification resulted in lower pH values during the first week, but in the long term, the conversion of glucose to carbonate led to higher pH values. A previous separation process was able to reduce the amount of acid. Although the pH increase was not that strong in the first days after acidification, it was much faster and stronger afterwards due to the lower buffer capacity in the separated slurry. A long-term pH reduction was achieved by acidification to pH 3.0, but this was associated with an increased amount of acid. On the basis of the results, a combination of organic acids with anaerobic storage can be recommended as an alternative to sulfuric acid.
Enhancing Sustainable Potato Production—A Case Study in Northern China
Authors: Wang Na , Reidsma Pytrik , Wang Ziquan , Zhou Xiaohan , Kempenaar Corné , Lv Dianqiu , van Ittersum Martin K.
Published: June 2021

Potato is the fourth most important staple crop in China. To meet the increased demand and environmental objectives, potato production should be enhanced by sustainable practices that aim to maximize yield and resource use efficiencies and minimize environmental impacts. Most experiments so far have taken place on experimental stations, while on-farm experimentation is needed to evaluate, demonstrate and scale more sustainable practices. On-farm field experiments were conducted in two years (2017, 2018) in northern China to investigate and demonstrate the effects of different nitrogen (N) fertiliser and irrigation input levels on potato yield, quality, resource use efficiency and environmental impacts. The 2017 experimental results on one farmer’s field showed that under irrigated conditions, adding N fertiliser (from 0 to 267 kg ha−1) did not increase yield due to the high soil N supply, rather it reduced tuber quality. The 2018 experimental results, in which four additional farmers were involved, indicated that, under irrigated conditions, reducing N fertiliser from the current rates (189–252 kg ha−1) to lower levels (109–181 kg ha−1) did not affect yield nor quality; while further reducing N fertiliser inputs (to 9–117 kg ha−1) resulted in a yield reduction (18% on average) in some fields. In both years, irrigation improved tuber yield and quality compared to that under rainfed conditions. The nitrogen use efficiency was improved and N surplus was reduced by applying irrigation and reducing N fertiliser input. Farmers expressed they were willing to reduce N fertiliser input by 10–20%, and indicated that a widespread adaptation of drip irrigation is hindered by the high costs and labor requirements. Site-specific recommendations on optimum N fertiliser and irrigation management must be provided, which should preferably be based on regular quantitative monitoring of soil N supply and soil moisture content.
Effects of Nitrogen and Water Deficiency on Agronomic Properties, Root Characteristics and Expression of Related Genes in Soybean
Authors: Hoffmann Borbála , Varga Balázs , Nagy Erzsébet , Hoffmann Sándor , Darkó Éva , Tajti Judit , Janda Tibor
Published: June 2021

Drought and insufficient nutrient supply are the main limiting factors for field crop production; therefore, the present study aimed to investigate the responses of four registered soybean varieties to limited nitrogen (N) supply in combination with drought stress. Plants were grown in tubes filled with silica sand, under open-air conditions. Water shortage was initiated at the three-leaf stage by providing 50% of water, and N deficiency was obtained by reducing the N content of the half-strength Hoagland solution by 50%. N deficiency did not influence the grain yield, while it significantly increased the root dry biomass in Boglár and Pannónia Kincse. Compared with nitrogen supply, the effects of the water shortage were dominant in root development. The expression levels of the investigated genes also showed genotypic variations. The expression of the Inducible nitrate reductase1 gene increased under N-deficient conditions in Boglár and decreased in Pannónia Kincse under drought conditions. The expression level of the aldehyde dehydrogenase gene and abscisic acid 8’-hydroxylase 3 increased under combined stress conditions. Summarising the agronomic and physiological characteristics, Boglár and Sinara were sensitive to drought, Bagera was sensitive to N deficiency but produced the highest yield under limited watering in each nitrogen treatment, while Pannónia Kincse was tolerant to nitrogen deficiency under well-watered conditions.
Lipid Peroxidation Assessment in Preclinical Alzheimer Disease Diagnosis
Authors: Peña-Bautista Carmen , Álvarez-Sánchez Lourdes , Ferrer Inés , López-Nogueroles Marina , Cañada-Martínez Antonio José , Oger Camille , Galano Jean-Marie , Durand Thierry , Baquero Miguel , Cháfer-Pericás Consuelo
Published: June 2021

Alzheimer disease (AD) is an increasingly common neurodegenerative disease, especially in countries with aging populations. Its diagnosis is complex and is usually carried out in advanced stages of the disease. In addition, lipids and oxidative stress have been related to AD since the earliest stages. A diagnosis in the initial or preclinical stages of the disease could help in a more effective action of the treatments. Isoprostanoid biomarkers were determined in plasma samples from preclinical AD participants (n = 12) and healthy controls (n = 31) by chromatography and mass spectrometry (UPLC-MS/MS). Participants were accurately classified according to cerebrospinal fluid (CSF) biomarkers and neuropsychological examination. Isoprostanoid levels did not show differences between groups. However, some of them correlated with CSF biomarkers (t-tau, p-tau) and with cognitive decline. In addition, a panel including 10 biomarkers showed an area under curve (AUC) of 0.96 (0.903–1) and a validation AUC of 0.90 in preclinical AD prediction. Plasma isoprostanoids could be useful biomarkers in preclinical diagnosis for AD. However, these results would require a further validation with an external cohort.