bluuebunny/crossref_metadata_2025 huggingface dataset:
LSTM Neural Network for Inferring Conduction Velocity Distribution in Demyelinating Neuropathies
Authors: Nodera Hiroyuki , Matsui Makoto
Published: July 2021

Waveform analysis of compound muscle action potential (CMAP) is important in the detailed analysis of conduction velocities of each axon as seen in temporal dispersion. This understanding is limited because conduction velocity distribution cannot be easily available from a CMAP waveform. Given the recent advent of artificial intelligence, this study aimed to assess whether conduction velocity (CV) distribution can be inferred from CMAP by the use of deep learning algorithms. Simulated CMAP waveforms were constructed from a single motor unit potential and randomly created CV histograms (n = 12,000). After training the data with various recurrent neural networks (RNNs), CV inference was tested by the network. Among simple RNNs, long short-term memory (LSTM) and gated recurrent unit, the best accuracy and loss profiles, were shown by two-layer bidirectional LSTM, with training and validation accuracies of 0.954 and 0.975, respectively. Training with the use of a recurrent neural network can accurately infer conduction velocity distribution in a wide variety of simulated demyelinating neuropathies. Using deep learning techniques, CV distribution can be assessed in a non-invasive manner.
Changes of the Brain Causal Connectivity Networks in Patients With Long-Term Bilateral Hearing Loss
Authors: Zhang Gang , Xu Long-Chun , Zhang Min-Feng , Zou Yue , He Le-Min , Cheng Yun-Fu , Zhang Dong-Sheng , Zhao Wen-Bo , Wang Xiao-Yan , Wang Peng-Cheng , Zhang Guang-Yu
Published: July 2021

It remains poorly understood how brain causal connectivity networks change following hearing loss and their effects on cognition. In the current study, we investigated this issue. Twelve patients with long-term bilateral sensorineural hearing loss [mean age, 55.7 ± 2.0; range, 39–63 years; threshold of hearing level (HL): left ear, 49.0 ± 4.1 dB HL, range, 31.25–76.25 dB HL; right ear, 55.1 ± 7.1 dB HL, range, 35–115 dB HL; the duration of hearing loss, 16.67 ± 4.5, range, 3–55 years] and 12 matched normally hearing controls (mean age, 52.3 ± 1.8; range, 42–63 years; threshold of hearing level: left ear, 17.6 ± 1.3 dB HL, range, 11.25–26.25 dB HL; right ear, 19.7 ± 1.3 dB HL, range, 8.75–26.25 dB HL) participated in this experiment. We constructed and analyzed the causal connectivity networks based on functional magnetic resonance imaging data of these participants. Two-sample t-tests revealed significant changes of causal connections and nodal degrees in the right secondary visual cortex, associative visual cortex, right dorsolateral prefrontal cortex, left subgenual cortex, and the left cingulate cortex, as well as the shortest causal connectivity paths from the right secondary visual cortex to Broca’s area in hearing loss patients. Neuropsychological tests indicated that hearing loss patients presented significant cognitive decline. Pearson’s correlation analysis indicated that changes of nodal degrees and the shortest causal connectivity paths were significantly related with poor cognitive performances. We also found a cross-modal reorganization between associative visual cortex and auditory cortex in patients with hearing loss. Additionally, we noted that visual and auditory signals had different effects on neural activities of Broca’s area, respectively. These results suggest that changes in brain causal connectivity network are an important neuroimaging mark of cognitive decline. Our findings provide some implications for rehabilitation of hearing loss patients.
Effects of Voluntary Running Wheel Exercise-Induced Extracellular Vesicles on Anxiety
Authors: Yoon Kyeong Jin , Park Suhong , Kwak Seung Hee , Moon Hyo Youl
Published: July 2021

Anxiety disorders are the most frequently diagnosed psychological condition, associated with serious comorbidities including excessive fear and interference with daily life. Drugs for anxiety disorders are typically prescribed but the side effects include weight gain, nausea, and sleepiness. Exercise is an effective treatment for anxiety. Exercise induces the release of extracellular vesicles (EVs) into the circulation, which transmit signals between organs. However, the effects of exercise-induced EVs on anxiety remain poorly understood. Here, we isolated EVs from the sera of mice that were sedentary or that voluntarily exercised. We characterized the changes in the miRNA profile of serum EVs after 4 weeks of voluntary exercise. miRNA sequencing showed that 82 miRNAs (46 of which were positive and 36 negative regulators) changed after exercise. We selected genes affected by at least two miRNAs. Of these, 27.27% were associated with neurotrophin signaling (9.09% with each of central nervous system neuronal development, cerebral cortical cell migration, and peripheral neuronal development). We also analyzed behavioral changes in mice with 3 weeks of restraint stress-induced anxiety after injection of 20 μg amounts of EVs from exercised or sedentary mice into the left cerebral ventricle. We found that exercise-derived EVs reduced anxiety (compared to a control group) in a nest-building test but found no between-group differences in the rotarod or open field tests. Exercise-derived EVs enhanced the expression of neuroactive ligand-receptor interaction genes. Thus, exercise-derived EVs may exhibit anti-anxiety effects and may be of therapeutic utility.
Delayed Meal Timing, a Breakfast Skipping Model, Increased Hepatic Lipid Accumulation and Adipose Tissue Weight by Disintegrating Circadian Oscillation in Rats Fed a High-Cholesterol Diet
Authors: Kim Daeun , Hanzawa Fumiaki , Sun Shumin , Laurent Thomas , Ikeda Saiko , Umeki Miki , Mochizuki Satoshi , Oda Hiroaki
Published: July 2021

Background: To investigate whether shifted timing of eating, breakfast skipping, induces alterations in the circadian clock and abnormal lipid metabolism, we have established a delayed meal timing (DMT) protocol for rats, which started eating food 4 h delay. In the present study, control and DMT rats were fed a high-cholesterol diet during zeitgeber time (ZT) 12-24 and ZT 16-4, respectively. The DMT protocol increased the hepatic lipids and epididymal adipose tissue weight without changes in food intake and body weight. The surge in body temperature was delayed by 4 h in the DMT group, suggesting that energy expenditure was decreased in response to DMT. The peaks of the diurnal rhythm of serum non-esterified fatty acids and insulin were delayed by 2 and 4 h due to DMT, respectively. The oscillation peaks of hepatic de novo fatty acid synthesis gene expression was delayed by 4 h in response to DMT, whereas the peak of hepatic clock genes were 2 h delayed or not by DMT. Although metabolic oscillation is considered to be controlled by clock genes, the disintegration rhythms between the clock genes and lipid metabolism-related genes were not observed in rats fed a high-fat diet in our previous study. These data suggest that the circadian rhythm of de novo fatty acid metabolism is regulated by timing of eating, but is not directly controlled by clock genes. The present study suggests that breakfast skipping would complicate fatty liver and body fat accumulation.
Eat Well to Fight Obesity… and Save Water: The Water Footprint of Different Diets and Caloric Intake and Its Relationship With Adiposity
Authors: Lares-Michel Mariana , Housni Fatima Ezzahra , Aguilera Cervantes Virginia Gabriela , Carrillo Presentación , Michel Nava Rosa María , Llanes Cañedo Claudia
Published: July 2021

Water scarcity and excess adiposity are two of the main problems worldwide and in Mexico, which is the most obese country in the world and suffers from water scarcity. Food production represents 90% of a person's water footprint (WF), and healthy diets can lead to less WF than do unhealthy diets related to obesity. We calculated the WF of the diet and caloric intake of adults in Mexico and analyzed its relationship with adiposity. Also, the risk of water expenditure due to adiposity and adherence to dietary recommendations regarding WF of international healthy diets were examined. A Food Consumption Frequency Questionnaire (FCFQ) was applied to 395 adults. Body mass index (BMI), associated with adiposity indicators, was used as a reference for grouping a sample into adiposity levels. The WF was calculated according to the WF Assessment Method, considering correction factors and accounting for water involved in cooking and food washing. Our results showed that the Mexican diet spends 6,056 liters per person per day (L p−1d−1) and is 55% higher than international healthy diets WF. Consumption of beef, milk, fruits, chicken, and fatty cereals represented 56% of total WF. Strong relations appeared between hypercaloric diets and high WF. Diets of people with excess adiposity generated statistically higher WF with extra expenses of 729 L p−1d−1 compared with the normal adiposity population. Following nutritional recommendations offers a protective factor in water care, whereas not adhering to these represents a risk up to 93 times greater of water expenditure regarding international healthy diets. Therefore, both for the general population and to regulate obesity, adequate diets can help mitigate the problem of water scarcity.
The Prognosis and Feasibility of Extensive Clinical Target Volume in Postoperative Radiotherapy for Esophageal Squamous Cell Carcinoma: A Phase II Clinical Trial
Authors: Zhang Xiaofei , Ai Dashan , Wang Juanqi , Chen Yun , Liu Qi , Deng Jiaying , Yang Huanjun , Nie Yongzhan , Chen Weiwei , Zhao Weixin , Zhao Kuaile
Published: July 2021

Background

This trial aims to explore the feasibility and safety of postoperative radiotherapy covering all regional lymph node areas for locally advanced thoracic esophageal squamous cell carcinoma patients treated with intensity-modulated radiation therapy (IMRT).

Methods

This was a single-center single-arm, phase II clinical trial initiated in 2014. Patients who were treated with radical transthoracic resection and had negative margins within 3 months and histologically confirmed esophageal squamous cell carcinoma (pT3-4 or N+, M0 determined by the 7th edition of the AJCC guidelines) were recruited in this trial. Postoperative radiotherapy was performed with a total dose of 40 Gy in 20 fractions using IMRT. Clinical target volumes (CTVs) included the tumor bed, anastomosis, bilateral supraclavicular region, mediastinal lymph nodes, left gastric lymph nodes and celiac trunk lymph nodes. The primary endpoint was the 2-year local control rate, and the secondary endpoints were overall survival (OS) and adverse events (AEs).

Results

A total of 70 eligible patients were recruited from 2014 to 2016. The 2-year local control rate, as the primary endpoint, was 67.3%. In addition, the median OS was 57.0 months, with 1-year and 3-year OS rates of 92.8% and 60.9%, respectively. Among the patients, 28/40 (40%) developed locoregional recurrence, with 25.7% involving hematogenous recurrences. All reported AEs occurred during the course of IMRT or within 6 months thereafter. None of them suffered grade 4 hematological or nonhematological AEs. Nearly all patients completed the entire course of postoperative radiotherapy, with a completion rate of 97.1%.

Conclusion

For an extensive target volume, 40 Gy is feasible and shows acceptable toxicity in patients with locally advanced thoracic esophageal squamous cell carcinoma, although the local recurrence rate is relatively high. Our findings provide a basis for further exploration of high-dose radiation with extensive CTV combined with chemotherapy.

Clinical Trial Registration

[http://www.clinicaltrials.gov/ct2/results?cond=&term=NCT02384811&cntry=&state=&city=&dist=], identifier [NCT02384811].
The WHO 2018 Classification of Cutaneous Melanocytic Neoplasms: Suggestions From Routine Practice
Authors: Ferrara Gerardo , Argenziano Giuseppe
Published: July 2021

The “multidimensional” World Health Organization (WHO) classification 2018 of melanocytic tumors encompasses nine melanoma pathways (seven of which for cutaneous melanoma) according to a progression model in which morphologically intermediate melanocytic tumors are cosidered as simulators and/or precursors to melanoma. These “intermediates” can be subclassified into: i) a “classical” subgroup (superficial/thin compound: dysplastic nevus), which is placed within the morphologic and molecular progression spectrum of classical (Clark’s and McGovern’s) melanoma subtypes (superficial spreading and, possibly, nodular); and ii) a “non-classical” subgroup (thick compound/dermal: “melanocytomas”) whose genetic pathways diverge from classical melanoma subtypes. Such a progression model is aimed at giving a conceptual framework for a histopathological classification; however, routine clinicopathological practice strongly suggests that most melanomas arise de novo and that the vast majority of nevi are clinically stable or even involuting over time. Clinicopathological correlation can help identify some severely atypical but benign tumors (e.g.: sclerosing nevus with pseudomelanomatous features) as well as some deceptively bland melanomas (e.g.: lentiginous melanoma; nested melanoma), thereby addressing some ambiguous cases to a correct clinical management. The recently available adjuvant therapy regimens for melanoma raise the problem of a careful distinction between severely atypical (high grade) melanocytoma and “classical” melanoma: conventional morphology can guide an algorithmic approach based on an antibody panel (anti-mutated BRAF, BAP1, PRAME, ALK, TRKA, MET, HRAS-WT, ROS; beta catenin; R1alpha; p16; HMB45; Ki67), a first-line molecular study (identification of hot spot mutations of BRAF and NRAS) and an advanced molecular study (sequencing of NF1, KIT, BRAF, MAP2K1, GNAQ, GNA11, PLCB4, CYSLTR2, HRAS; fusions studies of BRAF, RET, MAP3K8, PRKCA); as a final step, next-generation sequencing can identify melanocytic tumors with rare genetic signatures and melanocytic tumors with a high tumor mutation burden which should be definitely ascribed to the category of classical melanoma with the respective therapeutic options.
PGK1 Is a Key Target for Anti-Glycolytic Therapy of Ovarian Cancer: Based on the Comprehensive Analysis of Glycolysis-Related Genes
Authors: Gou Rui , Hu Yuexin , Liu Ouxuan , Dong Hui , Gao Lingling , Wang Shuang , Zheng Mingjun , Li Xiao , Lin Bei
Published: July 2021

Reprogramming of energy metabolism is a key hallmark of cancer, which provides a new research perspective for exploring the development of cancer. However, the most critical target of anti-glycolytic therapy for ovarian cancer remains unclear. Therefore, in the present study, Oncomine, GEPIA, and HPA databases, combined with clinical specimens of different histological types of ovarian cancer were used to comprehensively evaluate the expression levels of glycolysis-related metabolite transporters and enzymes in ovarian cancer. We selected phosphoglycerate kinase 1 (PGK1), which showed the greatest prognostic value in the Kaplan-Meier Plotter database, for subsequent validation. Immunochemistry assays confirmed that PGK1 was highly expressed in ovarian cancer. The PGK1 expression level was an independent risk factor for the survival and prognosis of patients with ovarian cancer. Functional analysis showed that the PGK1 expression level was positively correlated with the infiltration of neutrophils. Cell experiments confirmed that inhibiting PGK1 expression in ovarian cancer cells could reduce the epithelial-mesenchymal transition (EMT) process, resulting in loss of cell migration and invasion ability. The small molecule NG52 dose-dependently inhibited the proliferation of ovarian cancer cells. In addition, NG52 reduced the EMT process and reversed the Warburg effect by inhibiting PGK1 activity. Therefore, PGK1 is an attractive molecular target for anti-glycolytic therapy of ovarian cancer.
Current Molecular Biology and Therapeutic Strategy Status and Prospects for circRNAs in HBV-Associated Hepatocellular Carcinoma
Authors: Liao Rui , Liu Lei , Zhou Jian , Wei Xufu , Huang Ping
Published: July 2021

Circular RNAs (circRNAs) are newly classified noncoding RNA (ncRNA) members with a covalently closed continuous loop structure that are involved in immune responses against hepatitis B virus (HBV) infections and play important biological roles in the occurrence and pathogenesis of HCC progression. The roles of circRNAs in HBV-associated HCC (HBV-HCC) have gained increasing attention. Substantial evidence has revealed that both tissue and circulating circRNAs may serve as potential biomarkers for diagnostic, prognostic and therapeutic purposes. So far, at least four circRNA/miRNA regulatory axes such as circRNA_101764/miR-181, circRNA_100338/miR-141-3p, circ-ARL3/miR-1305, circ-ATP5H/miR-138-5p, and several circulating circRNAs were reported to be associated with HBV-HCC development. Notably, TGF/SMAD, JAK/STAT, Notch and Wnt/β-catenin signaling pathways may play pivotal roles in this HBV-driven HCC via several circRNAs. Moreover, in non-HBV HCC patients or HCC patients partially infected by HBV, numerous circRNAs have been identified to be important regulators impacting the malignant biological behavior of HCC. Furthermore, the role of circRNAs in HCC drug resistance has become a focus of research with the aim of reversing chemoresistance and immune resistance. Herein, we review the molecular biology of circRNAs in HBV-HCC and their potential in therapeutic strategies.
Predicting Treatment Response of Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Using Amide Proton Transfer MRI Combined With Diffusion-Weighted Imaging
Authors: Chen Weicui , Mao Liting , Li Ling , Wei Qiurong , Hu Shaowei , Ye Yongsong , Feng Jieping , Liu Bo , Liu Xian
Published: July 2021

Objective

To evaluate amide proton weighted (APTw) MRI combined with diffusion-weighted imaging (DWI) in predicting neoadjuvant chemoradiotherapy (NCRT) response in patients with locally advanced rectal cancer (LARC).

Methods

53 patients with LARC were enrolled in this retrospective study. MR examination including APTw MRI and DWI was performed before and after NCRT. APTw SI, ADC value, tumor size, CEA level before and after NCRT were assessed. The difference of the above parameters between before and after NCRT was calculated. The tumor regression grading (TRG) was assessed by American Joint Committee on Cancer’s Cancer Staging Manual AJCC 8th score. The Shapiro-Wilk test, paired t-test and Wilcoxon Signed Ranks test, two-sample t-test, Mann-Whitney U test and multivariate analysis were used for statistical analysis.

Results

Of the 53 patients, 19 had good responses (TRG 0-1), 34 had poor responses (TRG 2-3). After NCRT, all the rectal tumors demonstrated decreased APT values, increased ADC values, reduced tumor volumes and CEA levels (all p < 0.001). Good responders demonstrated higher pre-APT values, higher Δ APT values, lower pre- ADC values and higher Δ tumor volumes than poor responders. Pre-APT combined with pre-ADC achieved the best diagnostic performance, with AUC of 0.895 (sensitivity of 85.29%, specificity of 89.47%, p < 0.001) in predicting good response to NCRT.

Conclusion

The combination of APTw and DWI may serve as a noninvasive biomarker for evaluating and identifying response to NCRT in LARC patients.
Efficacy and Safety of Leflunomide for Refractory COVID-19: A Pilot Study
Authors: Wang Qiang , Guo Haipeng , Li Yu , Jian Xiangdong , Hou Xinguo , Zhong Ning , Fei Jianchun , Su Dezhen , Bian Zhouyan , Zhang Yi , Hu Yingying , Sun Yan , Yu Xueyuan , Li Yuan , Jiang Bei , Li Yan , Qin Fengping , Wu Yingying , Gao Yanxia , Hu Zhao
Published: July 2021

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may persist in patients with coronavirus disease 2019 (COVID-19) despite receiving standard care.

Methods: In this pilot study of hospitalized adult patients (≥18 years of age), with radiologically confirmed pneumonia who were SARS-CoV-2 positive for more than 28 days despite standard care, were assigned to receive standard of care (SOC, grp I) or leflunomide + SOC (grp 2). After 2 weeks, grp 1 and grp 2 patients who continued to be SARS-CoV-2-positive received leflunomide for 14 days while continuing SOC. The primary outcomes were the rate of and time to SARS-CoV-2 clearance and the 14-day and 30-day hospital discharge rate.

Results: 12 patients were enrolled in grp 1 and 15 patients were in grp 2. The 14 days SARS-CoV-2 viral clearance rate was 80.0% (12/15) for grp 2 patients receiving leflunomide vs. 16.7% for grp 1 patients (2/12) (p = 0.002). By day 14, the median time to SARS-CoV-2 clearance was 6.0 days (range 1–12, IQR 1–12) for grp 2 patients. In grp 1, two patients converted to viral negative on days 1 and 6 (p = 0.002). The 14-day discharge rate was 73.3% (11/15) for the grp 2 vs. 8.3% (1/12) for grp 1 (p = 0.001). The 30 days discharge rate was 100% (15/15) for the grp 2 vs. 66.7% (8/12) for grp 1. No severe adverse events or deaths were reported.

Conclusion: Leflunomide may improve the SARS-CoV-2 clearance rate and discharge rate in patients with refractory COVID-19. The tolerability of the 14–28 days course of treatment with leflunomide is acceptable. These preliminary observations need to be verified by a large sample size and randomized controlled trial.
Safe and Effective Treatment for Anemic Patients With Chronic Kidney Disease: An Updated Systematic Review and Meta-Analysis on Roxadustat
Authors: Tang Mei , Zhu Changyu , Yan Ting , Zhou Yanglin , Lv Qin , Chuan Junlan
Published: July 2021

Background: Roxadustat is a new oral drug for anemia in chronic kidney disease (CKD). This study aimed to synthesize the evidence from randomized controlled trial (RCT)-based studies that estimated the efficacy and safety of roxadustat in anemia patients with non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD.

Methods: We searched the PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for related published studies. Moreover, we manually searched relevant pharmaceutical company websites and two international clinical trial registers to search for published and unpublished RCTs comparing roxadustat with erythropoietin-stimulating agents (ESAs) or placebo.

Results: Fifteen RCTs (seven for DD-CKD patients, eight for NDD-CKD patients) were included in the meta-analysis, with 10,189 patients, 4,810 DD-CKD patients, and 5,379 NDD-CKD patients enrolled. Compared with ESAs (epoetin alfa or darbepoetin alfa) and placebo, roxadustat raised the hemoglobin level [weighted mean difference (WMD): 0.82 g/dL; 95% confidence interval (CI): 0.43–1.21], transferrin level (WMD: 0.5 g/L; 95% CI: 0.34–0.65), and TIBC level (WMD: 41.79 μg/dL; 95% CI: 38.67–44.92) and lowered the hepcidin level (WMD: −37.38 ng/ml; 95% CI: −46.63– −28.12) in both the DD-CKD and NDD-CKD patients with renal anemia. Roxadustat improved hemoglobin response and lowered the ferritin and TAST levels in the NDD-CKD patients but not in the DD-CKD patients. Furthermore, there was no difference between the treatment-emergent adverse events (TEAEs) of roxadustat and that of ESAs or placebo. But the incidence of serious TEAEs in the roxadustat group was significantly higher with NDD-CKD patients (OR: 1.15; 95% CI: 1.02–1.29).

Conclusion: This study confirmed that roxadustat therapy could alleviate the anemia of DD-CKD and NDD-CKD patients by raising the hemoglobin level and regulating iron metabolism, but increased serious incidences of treatment-emergent adverse events (TEAEs) in NDD-CKD patients.
Oxyhemoglobin Concentration and Oxygen Uptake Signal During Recovery From Exhaustive Exercise in Healthy Subjects—Relationship With Aerobic Capacity
Authors: Żebrowska Małgorzata , Weippert Matthias , Petelczyc Monika
Published: July 2021

This proof of concept study is dedicated to the quantification of the short-term recovery phase of the muscle oxygenation and whole-body oxygen uptake kinetics following an exhaustive cycling protocol. Data of 15 healthy young participants (age 26.1 ± 2.8 years, peak oxygen uptake 54.1 ± 5.1 mL∗min-1∗kg-1) were recorded during 5 min cool down-cycling with a power output of 50 W on an electro-magnetically braked cycle ergometer. The oxygen uptake (VO2) signal during recovery was modeled by exponential function. Using the model parameters, the time (T1/2) needed to return VO2 to 50% of VO2peak was determined. The Hill’s model was used to analyze the kinetics of oxyhemoglobin concentration (Sm, %), non-invasively recorded by near-infrared spectroscopy (NIRS) over the M. vastus lateralis. Analysis of the Pearson correlation results in statistically significant negative relationships between T1/2 and relative VO2peak (r = −0.7). Relevant significant correlations were determined between constant defining the slope of VO2 decrease (parameter B) and the duration of the anaerobic phase (r = −0.59), as well as between Hill’s coefficient and average median Smmax for the final 2 min of recovery. The high correlation between traditional variables commonly used to represent the cardio-metabolic capacity and the parameters of fits from exponential and Hill models attests the validity of our approach. Thus, proposed descriptors, derived from non-invasive NIRS monitoring during recovery, seem to reflect aerobic capacity. However, the practical usefulness of such modeling for clinical or other vulnerable populations has to be explored in studies using alternative testing protocols.
Antibodies Against the Clock Proteins Period and Cryptochrome Reveal the Neuronal Organization of the Circadian Clock in the Pea Aphid
Authors: Colizzi Francesca Sara , Beer Katharina , Cuti Paolo , Deppisch Peter , Martínez Torres David , Yoshii Taishi , Helfrich-Förster Charlotte
Published: July 2021

Circadian clocks prepare the organism to cyclic environmental changes in light, temperature, or food availability. Here, we characterized the master clock in the brain of a strongly photoperiodic insect, the aphid Acyrthosiphon pisum, immunohistochemically with antibodies against A. pisum Period (PER), Drosophila melanogaster Cryptochrome (CRY1), and crab Pigment-Dispersing Hormone (PDH). The latter antibody detects all so far known PDHs and PDFs (Pigment-Dispersing Factors), which play a dominant role in the circadian system of many arthropods. We found that, under long days, PER and CRY are expressed in a rhythmic manner in three regions of the brain: the dorsal and lateral protocerebrum and the lamina. No staining was detected with anti-PDH, suggesting that aphids lack PDF. All the CRY1-positive cells co-expressed PER and showed daily PER/CRY1 oscillations of high amplitude, while the PER oscillations of the CRY1-negative PER neurons were of considerable lower amplitude. The CRY1 oscillations were highly synchronous in all neurons, suggesting that aphid CRY1, similarly to Drosophila CRY1, is light sensitive and its oscillations are synchronized by light-dark cycles. Nevertheless, in contrast to Drosophila CRY1, aphid CRY1 was not degraded by light, but steadily increased during the day and decreased during the night. PER was always located in the nuclei of the clock neurons, while CRY was predominantly cytoplasmic and revealed the projections of the PER/CRY1-positive neurons. We traced the PER/CRY1-positive neurons through the aphid protocerebrum discovering striking similarities with the circadian clock of D. melanogaster: The CRY1 fibers innervate the dorsal and lateral protocerebrum and putatively connect the different PER-positive neurons with each other. They also run toward the pars intercerebralis, which controls hormone release via the neurohemal organ, the corpora cardiaca. In contrast to Drosophila, the CRY1-positive fibers additionally travel directly toward the corpora cardiaca and the close-by endocrine gland, corpora allata. This suggests a direct link between the circadian clock and the photoperiodic control of hormone release that can be studied in the future.
TheLNet270v1 – A Novel Deep-Network Architecture for the Automatic Classification of Thermal Images for Greenhouse Plants
Authors: Islam Md. Parvez , Nakano Yuka , Lee Unseok , Tokuda Keinichi , Kochi Nobuo
Published: July 2021

The real challenge for separating leaf pixels from background pixels in thermal images is associated with various factors such as the amount of emitted and reflected thermal radiation from the targeted plant, absorption of reflected radiation by the humidity of the greenhouse, and the outside environment. We proposed TheLNet270v1 (thermal leaf network with 270 layers version 1) to recover the leaf canopy from its background in real time with higher accuracy than previous systems. The proposed network had an accuracy of 91% (mean boundary F1 score or BF score) to distinguish canopy pixels from background pixels and then segment the image into two classes: leaf and background. We evaluated the classification (segment) performance by using more than 13,766 images and obtained 95.75% training and 95.23% validation accuracies without overfitting issues. This research aimed to develop a deep learning technique for the automatic segmentation of thermal images to continuously monitor the canopy surface temperature inside a greenhouse.
Optimizing Genomic-Enabled Prediction in Small-Scale Maize Hybrid Breeding Programs: A Roadmap Review
Authors: Fritsche-Neto Roberto , Galli Giovanni , Borges Karina Lima Reis , Costa-Neto Germano , Alves Filipe Couto , Sabadin Felipe , Lyra Danilo Hottis , Morais Pedro Patric Pinho , Braatz de Andrade Luciano Rogério , Granato Italo , Crossa Jose
Published: July 2021

The usefulness of genomic prediction (GP) for many animal and plant breeding programs has been highlighted for many studies in the last 20 years. In maize breeding programs, mostly dedicated to delivering more highly adapted and productive hybrids, this approach has been proved successful for both large- and small-scale breeding programs worldwide. Here, we present some of the strategies developed to improve the accuracy of GP in tropical maize, focusing on its use under low budget and small-scale conditions achieved for most of the hybrid breeding programs in developing countries. We highlight the most important outcomes obtained by the University of São Paulo (USP, Brazil) and how they can improve the accuracy of prediction in tropical maize hybrids. Our roadmap starts with the efforts for germplasm characterization, moving on to the practices for mating design, and the selection of the genotypes that are used to compose the training population in field phenotyping trials. Factors including population structure and the importance of non-additive effects (dominance and epistasis) controlling the desired trait are also outlined. Finally, we explain how the source of the molecular markers, environmental, and the modeling of genotype–environment interaction can affect the accuracy of GP. Results of 7 years of research in a public maize hybrid breeding program under tropical conditions are discussed, and with the great advances that have been made, we find that what is yet to come is exciting. The use of open-source software for the quality control of molecular markers, implementing GP, and envirotyping pipelines may reduce costs in an efficient computational manner. We conclude that exploring new models/tools using high-throughput phenotyping data along with large-scale envirotyping may bring more resolution and realism when predicting genotype performances. Despite the initial costs, mostly for genotyping, the GP platforms in combination with these other data sources can be a cost-effective approach for predicting the performance of maize hybrids for a large set of growing conditions.
Comparison of Transcriptional Response of C3 and C4 Plants to Drought Stress Using Meta-Analysis and Systems Biology Approach
Authors: Tahmasebi Ahmad , Niazi Ali
Published: July 2021

Drought stress affects a range of plant processes. It is still not well-known how C3 and C4 plants respond to drought. Here, we used a combination of meta-analysis and network analysis to compare the transcriptional responses of Oryza sativa (rice), a C3 plant, and Zea mays (maize), a C4 plant, to drought stress. The findings showed that drought stress changes the expression of genes and affects different mechanisms in the C3 and C4 plants. We identified several genes that were differentially expressed genes (DEGs) under stress conditions in both species, most of which are associated with photosynthesis, molecule metabolic process, and response to stress. Additionally, we observed that many DEGs physically located within the quantitative trait locus regions are associated with C isotope signature (d13C), photosynthetic gas exchange, and root characteristics traits. Through the gene co-expression and differential co-expression network methods, we identified sets of genes with similar and different behaviors among C3 and C4 plants during drought stress. This result indicates that mitogen-activated protein kinases (MAPK) signaling pathway plays an important part in the differences between the C3 and C4 species. The present study provides a better understanding of the mechanisms underlying the response of C3 and C4 plants to drought stress, which may useful for engineering drought tolerance in plants.
How and Why Patient Concerns Influence Pain Reporting: A Qualitative Analysis of Personal Accounts and Perceptions of Others’ Use of Numerical Pain Scales
Authors: Boring Brandon L. , Walsh Kaitlyn T. , Nanavaty Namrata , Ng Brandon W. , Mathur Vani A.
Published: July 2021

Complex factors influence how people report and interpret numerical pain ratings. Such variability can introduce noise and systematic bias into clinical pain assessment. Identification of factors that influence self-rated pain and its interpretation by others may bolster utility of these scales. In this qualitative study, 338 participants described motivations for modulating their own pain reports relative to a numerical pain scale (0–10), as well as perceptions of others’ pain reporting modulation. Responses indicated that people over-report pain to enhance provider belief/responsiveness or the likelihood of pain relief, and out of fear of future pain or potential illness. Concerns of how one’s pain affects and is perceived by others, and financial concerns motivated pain under-reporting. Unprompted, many participants reported never modulating their pain ratings, citing trust in providers and personal ethics. Similar reasons were assumed to motivate others’ pain ratings. However, participants often attributed others’ over-reporting to internal causes, and their own to external. This bias may underlie common assumptions that patients over-report pain for nefarious reasons, distort interpretation of pain reports, and contribute to pain invalidation. Recognition of patient concerns and one’s own personal biases toward others’ pain reporting may improve patient-provider trust and support precision of numerical pain ratings.
Systematic Review of the Economic Evaluation of Returning Incidental Findings in Genomic Research
Authors: Fontes Marx Mayara , Ataguba John E. , Vries Jantina de , Wonkam Ambroise
Published: July 2021

Objectives: Discussions regarding who and how incidental findings (IFs) should be returned and the ethics behind returning IFs have increased dramatically over the years. However, information on the cost and benefits of returning IFs to patients remains scanty.

Design: This study systematically reviews the economic evaluation of returning IFs in genomic sequencing. We searched for published articles on the cost-effectiveness, cost-benefit, and cost-utility of IFs in Medline, Scopus, PubMed, and Google Scholar.

Results: We found six published articles that met the eligibility criteria of this study. Two articles used cost analysis only, one used cost-benefit analysis only, two used both cost analysis and cost-effectiveness, and one used both cost-benefit analysis and cost-utility to describe the cost of returning IFs in genomic sequencing.

Conclusion: While individuals value the IF results and are willing to pay for them, the cost of returning IFs depends on the primary health condition of the patient. Although patients were willing to pay, there was no clear evidence that returning IFs might be cost-effective. More rigorous economic evaluation studies of IFs are needed to determine whether or not the cost of returning IFs is beneficial to the patient.
Use of Pulsed Electric Field as a Low-Temperature and High-Performance “Green” Extraction Technique for the Recovery of High Added Value Compounds from Olive Leaves
Authors: Pappas Vasileios M. , Lakka Achillia , Palaiogiannis Dimitrios , Bozinou Eleni , Ntourtoglou George , Batra Georgia , Athanasiadis Vassilis , Makris Dimitris P. , Dourtoglou Vassilis G. , Lalas Stavros I.
Published: July 2021

Olive leaves (OLL), an agricultural waste by-product, are considered a significant bioresource of polyphenols, known as bioactive compounds. This study evaluates the pulsed electric field (PEF) technique for the extraction of polyphenols from OLL. The study parameters included a series of “green” solvents (ethanol, water as well as mixtures of them at a 25% step gradient) and different input values for the pulse duration of PEF. The phytochemical extraction degree was evaluated using total phenol concentration (Folin–Ciocalteu method) and high-performance liquid chromatography (HPLC) analyses, while the antioxidant activity was assessed using differential scanning calorimetry (DSC). The results obtained from the PEF extracts were compared with those of the extracts produced without the PEF application. The highest PEF effect was observed for aqueous ethanol, 25% v/v, using a pulse duration of 10 μs. The increase in the total polyphenols reached 31.85%, while the increase in the specific metabolites reached 265.67%. The recovery in polyphenols was found to depend on the solvent, the pulse duration of treatment and the structure of the metabolites extracted.
Bioremediation of Agricultural Soils Polluted with Pesticides: A Review
Authors: Raffa Carla Maria , Chiampo Fulvia
Published: July 2021

Pesticides are chemical compounds used to eliminate pests; among them, herbicides are compounds particularly toxic to weeds, and this property is exploited to protect the crops from unwanted plants. Pesticides are used to protect and maximize the yield and quality of crops. The excessive use of these chemicals and their persistence in the environment have generated serious problems, namely pollution of soil, water, and, to a lower extent, air, causing harmful effects to the ecosystem and along the food chain. About soil pollution, the residual concentration of pesticides is often over the limits allowed by the regulations. Where this occurs, the challenge is to reduce the amount of these chemicals and obtain agricultural soils suitable for growing ecofriendly crops. The microbial metabolism of indigenous microorganisms can be exploited for degradation since bioremediation is an ecofriendly, cost-effective, rather efficient method compared to the physical and chemical ones. Several biodegradation techniques are available, based on bacterial, fungal, or enzymatic degradation. The removal efficiencies of these processes depend on the type of pollutant and the chemical and physical conditions of the soil. The regulation on the use of pesticides is strictly connected to their environmental impacts. Nowadays, every country can adopt regulations to restrict the consumption of pesticides, prohibit the most harmful ones, and define the admissible concentrations in the soil. However, this variability implies that each country has a different perception of the toxicology of these compounds, inducing different market values of the grown crops. This review aims to give a picture of the bioremediation of soils polluted with commercial pesticides, considering the features that characterize the main and most used ones, namely their classification and their toxicity, together with some elements of legislation into force around the world.
Interlink between Inflammation and Oxidative Stress in Age-Related Macular Degeneration: Role of Complement Factor H
Authors: Romero-Vazquez Sara , Llorens Víctor , Soler-Boronat Alba , Figueras-Roca Marc , Adan Alfredo , Molins Blanca
Published: July 2021

Age-related macular degeneration (AMD) heads the list of legal blindness among the elderly population in developed countries. Due to the complex nature of the retina and the variety of risk factors and mechanisms involved, the molecular pathways underlying AMD are not yet fully defined. Persistent low-grade inflammation and oxidative stress eventually lead to retinal pigment epithelium dysfunction and outer blood–retinal barrier (oBRB) breakdown. The identification of AMD susceptibility genes encoding complement factors, and the presence of inflammatory mediators in drusen, the hallmark deposits of AMD, supports the notion that immune-mediated processes are major drivers of AMD pathobiology. Complement factor H (FH), the main regulator of the alternative pathway of the complement system, may have a key contribution in the pathogenesis of AMD as it is able to regulate both inflammatory and oxidative stress responses in the oBRB. Indeed, genetic variants in the CFH gene account for the strongest genetic risk factors for AMD. In this review, we focus on the roles of inflammation and oxidative stress and their connection with FH and related proteins as regulators of both phenomena in the context of AMD.
High Resolution Episcopic Microscopy for Qualitative and Quantitative Data in Phenotyping Altered Embryos and Adult Mice Using the New “Histo3D” System
Authors: Wendling Olivia , Hentsch Didier , Jacobs Hugues , Lemercier Nicolas , Taubert Serge , Pertuy Fabien , Vonesch Jean-Luc , Sorg Tania , Di Michele Michela , Le Cam Laurent , Rosahl Thomas , Carballo-Jane Ester , Liu Mindy , Mu James , Mark Manuel , Herault Yann
Published: July 2021

3D imaging in animal models, during development or in adults, facilitates the identification of structural morphological changes that cannot be achieved with traditional 2D histological staining. Through the reconstruction of whole embryos or a region-of-interest, specific changes are better delimited and can be easily quantified. We focused here on high-resolution episcopic microscopy (HREM), and its potential for visualizing and quantifying the organ systems of normal and genetically altered embryos and adult organisms. Although the technique is based on episcopic images, these are of high resolution and are close to histological quality. The images reflect the tissue structure and densities revealed by histology, albeit in a grayscale color map. HREM technology permits researchers to take advantage of serial 2D aligned stacks of images to perform 3D reconstructions. Three-dimensional visualization allows for an appreciation of topology and morphology that is difficult to achieve with classical histological studies. The nature of the data lends itself to novel forms of computational analysis that permit the accurate quantitation and comparison of individual embryos in a manner that is impossible with histology. Here, we have developed a new HREM prototype consisting of the assembly of a Leica Biosystems Nanocut rotary microtome with optics and a camera. We describe some examples of applications in the prenatal and adult lifestage of the mouse to show the added value of HREM for phenotyping experimental cohorts to compare and quantify structure volumes. At prenatal stages, segmentations and 3D reconstructions allowed the quantification of neural tissue and ventricular system volumes of normal brains at E14.5 and E16.5 stages. 3D representations of normal cranial and peripheric nerves at E15.5 and of the normal urogenital system from stages E11.5 to E14.5 were also performed. We also present a methodology to quantify the volume of the atherosclerotic plaques of ApoEtm1Unc/tm1Unc mutant mice and illustrate a 3D reconstruction of knee ligaments in adult mice.
The Potential Role of Extracorporeal Cytokine Removal in Hemodynamic Stabilization in Hyperinflammatory Shock
Authors: Hawchar Fatime , Rao Cristina , Akil Ali , Mehta Yatin , Rugg Christopher , Scheier Joerg , Adamson Harriet , Deliargyris Efthymios , Molnar Zsolt
Published: July 2021

Hemodynamic instability due to dysregulated host response is a life-threatening condition requiring vasopressors and vital organ support. Hemoadsorption with Cytosorb has proven to be effective in reducing cytokines and possibly in attenuating the devastating effects of the cytokine storm originating from the immune over-response to the initial insult. We reviewed the PubMed database to assess evidence of the impact of Cytosorb on norepinephrine needs in the critically ill. We further analyzed those studies including data on control cohorts in a comparative pooled analysis, defining a treatment effect as the standardized mean differences in relative reductions in vasopressor dosage at 24 h. The literature search returned 33 eligible studies. We found evidence of a significant reduction in norepinephrine requirement after treatment: median before, 0.55 (IQR: 0.39–0.90); after, 0.09 (0.00–0.25) μg/kg/min, p < 0.001. The pooled effect size at 24 h was large, though characterized by high heterogeneity. In light of the importance of a quick resolution of hemodynamic instability in the critically ill, further research is encouraged to enrich knowledge on the potentials of the therapy.
BODIPY-Pyridylhydrazone Probe for Fluorescence Turn-On Detection of Fe3+ and Its Bioimaging Application
Authors: Nootem Jukkrit , Sattayanon Chanchai , Daengngern Rathawat , Kamkaew Anyanee , Wattanathana Worawat , Wannapaiboon Suttipong , Rashatasakhon Paitoon , Chansaenpak Kantapat
Published: July 2021

A novel pyridylhydrazone-tethered BODIPY (BODIPY-PH) was synthesized, fully characterized via nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopic (FTIR), and single-crystal X-ray diffraction (SC-XRD) techniques, and developed for the selective detection of Fe3+ through fluorescent enhancement process. This derivative showed 1:1 binding with Fe3+ in an acetonitrile-water mixture (1:9 v/v) with the binding constant (K) of 5.4 × 104 M−1 and the limit of detection of 0.58 µM. The Fe3+ complexation reaction has been proved to be a reversible process and could be effectively repeated up to three cycles. The electronic properties of BODIPY-PH and its Fe3+ complex modeled by the density functional theory (DFT) method suggested the presence of chelation-enhanced fluorescence (CHEF) effect in the Fe3+ binding reaction. The X-ray absorption spectroscopy (XAS) probed at Fe K-edge confirmed the complex formation between BODIPY-PH and the Fe3+ in an octahedral geometry. Finally, bioimaging against human embryonic kidney (Hek293) cell, through confocal fluorescence microscopic technique indicated that the BODIPY-PH displayed good permeability and low toxicity toward the tested cell lines and showed enhanced fluorescent signal in the cells incubated with Fe3+ proving its capability for Fe3+ analysis in cellular matrix.