bluuebunny/crossref_metadata_2025 huggingface dataset:
Photonic spiking neural networks with event-driven femtojoule optoelectronic neurons based on Izhikevich-inspired model
Authors: Lee Yun-Jhu , On Mehmet Berkay , Xiao Xian , Proietti Roberto , Yoo S. J. Ben
Published: April 2022

Photonic spiking neural networks (PSNNs) potentially offer exceptionally high throughput and energy efficiency compared to their electronic neuromorphic counterparts while maintaining their benefits in terms of event-driven computing capability. While state-of-the-art PSNN designs require a continuous laser pump, this paper presents a monolithic optoelectronic PSNN hardware design consisting of an MZI mesh incoherent network and event-driven laser spiking neurons. We designed, prototyped, and experimentally demonstrated this event-driven neuron inspired by the Izhikevich model incorporating both excitatory and inhibitory optical spiking inputs and producing optical spiking outputs accordingly. The optoelectronic neurons consist of two photodetectors for excitatory and inhibitory optical spiking inputs, electrical transistors’ circuits providing spiking nonlinearity, and a laser for optical spiking outputs. Additional inclusion of capacitors and resistors complete the Izhikevich-inspired optoelectronic neurons, which receive excitatory and inhibitory optical spikes as inputs from other optoelectronic neurons. We developed a detailed optoelectronic neuron model in Verilog-A and simulated the circuit-level operation of various cases with excitatory input and inhibitory input signals. The experimental results closely resemble the simulated results and demonstrate how the excitatory inputs trigger the optical spiking outputs while the inhibitory inputs suppress the outputs. The nanoscale neuron designed in our monolithic PSNN utilizes quantum impedance conversion. It shows that estimated 21.09 fJ/spike input can trigger the output from on-chip nanolasers running at a maximum of 10 Gspike/second in the neural network. Utilizing the simulated neuron model, we conducted simulations on MNIST handwritten digits recognition using fully connected (FC) and convolutional neural networks (CNN). The simulation results show 90% accuracy on unsupervised learning and 97% accuracy on a supervised modified FC neural network. The benchmark shows our PSNN can achieve 50 TOP/J energy efficiency, which corresponds to 100 × throughputs and 1000 × energy-efficiency improvements compared to state-of-art electrical neuromorphic hardware such as Loihi and NeuroGrid.
Adaptive digital back propagation exploiting adjoint-based optimization for fiber-optic communications
Authors: Maghrabi Mahmoud M. T. , Bakr Mohamed H. , Kumar Shiva
Published: April 2022

This work proposes a novel and powerful adaptive digital back propagation (A-DBP) method with a fast adaption process. Given that the total transmission distance is known, the proposed A-DBP algorithm blindly compensates for the linear and nonlinear distortions of optical fiber transmission systems and networks, without knowing the launch power and channel parameters. An adjoint-based optimization (ABO) technique is proposed to significantly accelerate the parameters estimation of the A-DBP. The ABO algorithm utilizes a sequential quadratic programming (SQP) method coupled with an adjoint sensitivity analysis (ASA) approach to rapidly solve the A-DBP training problem. The design parameters are optimized using the minimum overhead of only one extra system simulation. Regardless of the number of A-DBP design parameters, the derivatives of the training objective function with respect to all parameters are estimated using only one extra adjoint system simulation per optimization iterate. This is contrasted with the traditional finite-difference (FD)-based optimization methods whose sensitivity analysis calculations cost per iterate scales linearly with the number of parameters. The robustness, performance, and efficiency of the proposed A-DBP algorithm are demonstrated through applying it to mitigate the distortions of 4-span and 20-span optical fiber communication systems. Coarse-mesh A-DBPs with less number of virtual spans are also used to significantly reduce the computational complexity of the equalizer, achieving compensation performance higher than that obtained using the coarse-mesh DBP with the exact channel parameters and full number of virtual spans.
Diagnosis of HLB-asymptomatic citrus fruits by element migration and transformation using laser-induced breakdown spectroscopy
Authors: Yang Ping , Nie Zhanglong , Yao Mingyin
Published: April 2022

Huanglongbing (HLB) is one of the most devastating bacterial diseases in citrus growth and there is no cure for it. The mastery of elemental migration and transformation patterns can effectively analyze the growth of crops. The law of element migration and transformation in citrus growth is not very clear. In order to obtain the law of element migration and transformation, healthy and HLB-asymptomatic navel oranges collected in the field were taken as research objects. Laser-induced breakdown spectroscopy (LIBS) is an atomic spectrometry technique for material component analysis. By analyzing the element composition of fruit flesh, peel and soil, it can know the specific process of nutrient exchange and energy exchange between plants and the external environment, as well as the rules of internal nutrient transportation, distribution and energy transformation. Through the study of elemental absorption, the growth of navel orange can be effectively monitored in real time. HLB has an inhibitory effect on the absorption of navel orange. In order to improve the detection efficiency, LIBS coupled with SVM algorithms was used to distinguish healthy navel oranges and HLB-asymptomatic navel oranges. The classification accuracy was 100%. Compared with the traditional detection method, the detection efficiency of LIBS technology is significantly better than the polymerase chain reaction method, which provides a new means for the diagnosis of HLB-asymptomatic citrus fruits.
Demonstration of a multicolor metasurface holographic movie based on a cinematographic approach
Authors: Yamada Naoyuki , Saito Hiroki , Ikezawa Satoshi , Iwami Kentaro
Published: April 2022

This study uses a dielectric metasurface to demonstrates a multicolor holographic movie. Overlapping of multiple-wavelength images at 445 nm, 532 nm, and 633 nm was achieved by maintaining the ratio between the wavelengths and the pixel periods constant. Polarization-independent pillar waveguides made of single-crystal silicon are used as meta-atoms. A movie of the rotating earth was designed by the iterative Fourier transform algorithm and fabricated using electron beam lithography to a silicon-on-sapphire substrate. The multicolor movie consists of 20 frames was successfully reproduced at the maximum speed of 30 frames per second.
Intrinsically accurate sensing with an optomechanical accelerometer
Authors: Reschovsky Benjamin J. , Long David A. , Zhou Feng , Bao Yiliang , Allen Richard A. , LeBrun Thomas W. , Gorman Jason J.
Published: April 2022

We demonstrate a microfabricated optomechanical accelerometer that is capable of percent-level accuracy without external calibration. To achieve this capability, we use a mechanical model of the device behavior that can be characterized by the thermal noise response along with an optical frequency comb readout method that enables high sensitivity, high bandwidth, high dynamic range, and SI-traceable displacement measurements. The resulting intrinsic accuracy was evaluated over a wide frequency range by comparing to a primary vibration calibration system and local gravity. The average agreement was found to be 2.1 % for the calibration system between 0.1 kHz and 15 kHz and better than 0.2 % for the static acceleration. This capability has the potential to replace costly external calibrations and improve the accuracy of inertial guidance systems and remotely deployed accelerometers. Due to the fundamental nature of the intrinsic accuracy approach, it could be extended to other optomechanical transducers, including force and pressure sensors.
Patagonian sheepdog: Genomic analyses trace the footprints of extinct UK herding dogs to South America
Authors: Barrios Natasha , González-Lagos César , Dreger Dayna L. , Parker Heidi G. , Nourdin-Galindo Guillermo , Hogan Andrew N. , Gómez Marcelo A. , Ostrander Elaine A.
Published: April 2022

Most modern dog breeds were developed within the last two hundred years, following strong and recent human selection based predominantly on aesthetics, with few modern breeds constructed solely to maximize their work potential. In many cases, these working breeds represent the last remnants of now lost populations. The Patagonian sheepdog (PGOD), a rare herding breed, is a remarkable example of such a population. Maintained as an isolated population for over 130 years, the PGOD offers a unique opportunity to understand the genetic relationship amongst modern herding breeds, determine key genomic structure of the founder PGOD populations, and investigate how canine genomic data can mirror human migration patterns. We thus analyzed the population structure of 159 PGOD, comparing them with 1514 dogs representing 175 established breeds. Using 150,069 SNPs from a high-density SNP genotyping array, we establish the genomic composition, ancestry, and genetic diversity of the population, complementing genomic data with the PGOD’s migratory history to South America. Our phylogenetic analysis reveals that PGODs are most closely related to modern herding breeds hailing from the United Kingdom. Admixture models illustrate a greater degree of diversity and genetic heterogeneity within the very small PGOD population than in Western European herding breeds, suggesting the PGOD predates the 200-year-old construction of most pure breeds known today. We thus propose that PGODs originated from the foundational herding dogs of the UK, prior to the Victorian explosion of breeds, and that they are the closest link to a now-extinct population of herding dogs from which modern herding breeds descended.
Bayesian modeling and simulation to inform rare disease drug development early decision-making: Application to Duchenne muscular dystrophy
Authors: Lennie Janelle L. , Mondick John T. , Gastonguay Marc R.
Published: April 2022

Rare disease clinical trials are constrained to small sample sizes and may lack placebo-control, leading to challenges in drug development. This paper proposes a Bayesian model-based framework for early go/no-go decision making in rare disease drug development, using Duchenne muscular dystrophy (DMD) as an example. Early go/no-go decisions were based on projections of long-term functional outcomes from a Bayesian model-based analysis of short-term trial data informed by prior knowledge based on 6MWT natural history literature data in DMD patients. Frequentist hypothesis tests were also applied as a reference analysis method. A number of combinations of hypothetical trial designs, drug effects and cohort comparison methods were assessed. The proposed Bayesian model-based framework was superior to the frequentist method for making go/no-go decisions across all trial designs and cohort comparison methods in DMD. The average decision accuracy rates across all trial designs for the Bayesian and frequentist analysis methods were 45.8 and 8.98%, respectively. A decision accuracy rate of at least 50% was achieved for 42 and 7% of the trial designs under the Bayesian and frequentist analysis methods, respectively. The frequentist method was limited to the short-term trial data only, while the Bayesian methods were informed with both the short-term data and prior information. The specific results of the DMD case study were limited due to incomplete specification of individual-specific covariates in the natural history literature data and should be reevaluated using a full natural history dataset. These limitations aside, the framework presented provides a proof of concept for the utility of Bayesian model-based methods for decision making in rare disease trials.
DNA metabarcoding uncovers the diet of subterranean rodents in China
Authors: Zhang Xuxin , Zou Yao , Zou Xuan , Xu Zhenggang , Nan Xiaoning , Han Chongxuan
Published: April 2022

Objective

A type of rodent called a zokor causes great harm to agriculture and forestry production due to its large and sophisticated diet. As this rodent lives subterrane for most of its life, researchers know little about its dietary habits. Further understanding of its diet is important for developing green and sustainable control strategies for the zokor.

Methods

Chloroplast trnL gene and internal transcription spacer 1 primers were selected for high-throughput sequencing of stomach contents of captured zokor by DNA metabarcoding.

Results

A total of 25 zokors were selected, the food list of 32 families, 80 genera, and 154 species was obtained. At the family level, it was found that zokors mainly fed on Asteraceae, Poaceae, Rosaceae, Pinaceae, Brassicaceae, and Apiaceae. At the genus level, zokors mainly fed on Echinops, Littledalea, Artemisia, Picea, Cirsium, and Elymus. The diet alpha diversity of Eospalax cansus was slightly higher than that of Eospalax cansus (P>0.05). The zokor’s diet is highly phconsistent with the resources of its habitat. Most food choices tend to be the same between the two zokors. They fed primarily on Calamagrostis, Cirsium, Echinops, Medicago, Sanguisorba, and Taraxacum. Zokors mainly fed on the roots of perennial herbs, which are important source of energy.

Conclusion

High-throughput sequencing-based DNA metabarcoding technology has effectively revealed the diet of zokors and indicated that zokors are food generalists.
The impact of newly synthesized sulfonamides on soil microbial population and respiration in rhizospheric soil of wheat (Triticum aestivum L.)
Authors: Saleem Ammara , Zulfiqar Asma , Arshed Muhammad Zeeshan , Hussain Saber , Khan Muhammad Tajammal , Zivcak Marek , Zuan Ali Tan Kee , Alshahrani Shrouq M. , Alarjani Khaloud Mohammed
Published: April 2022

Antibiotics released into agricultural fields through the manure of grazing animals could exert harmful impacts on soil microbes and plants. Antibiotics exert high impacts on environment than other pharmaceuticals due to their higher biological activity. However, little is known about their impacts on plants, despite indications that antibiotics exert negative effects on soil microorganisms, which ultimately harm the plants. It has been demonstrated that beneficial microorganisms promote plant growth and development under various stresses. This study evaluated the toxicity of four newly derived sulfonamides (SAs), i.e., 2-(phenylsulfonyl) hydrazine carbothioamide (TSBS-1), N, 2-bis phenyl hydrazine carbothioamide (TSBS-2), aminocarbonyl benzene sulfonamide (UBS-1), and N, N’-carbonyl dibenzene sulfonamide (UBS-2) on bacterial growth and soil microbial respiration. Each SA was tested at four different concentrations (i.e., 2.25, 2.5, 3, 4 mg/ml) against five rhizospheric bacterial strains, including AC (Actinobacteria sp.), RS-3a (Bacillus sp.), RS-7a (Bacillus subtilis), RS-4a (Enterobacter sp.), and RS-5a (Enterobacter sp.). Antimicrobial activity was checked by disc diffusion method, which showed that inhibition zone increased with increasing concentration of SAs. The UBS-1 resulted in the highest inhibition zone (11.47 ± 0.90 mm) against RS-4a with the highest concentration (4 mg/ml). Except TSBS-1, all sulfonamide derivatives reduced CO2 respiration rates in soil. Soil respiration values significantly increased till 6th day; however, exposure of sulfonamide derivatives suppressed microbial respiration after 6th day. On the 20th day, poor respiration activity was noted at 0.23, 0.2, and 0.4 (CO2 mg/g dry soil) for TSBS-1, UBS-1, and UBS-2, respectively. Our results demonstrate that sulfonamides, even in small concentrations, significantly affect soil microbial population and respiration. Soil microbial respiration changes mediated by sulfonamides were dependent on length of exposure and concentration. It is recommended that antibiotics should be carefully watched and their impact on plant growth should be tested in the future studies.
MafB, WDR77, and ß-catenin interact with each other and have similar genome association profiles
Authors: He Lizhi , Gao Mingshi , Pratt Henry , Weng Zhiping , Struhl Kevin
Published: April 2022

MafB (a bZIP transcription factor), ß-catenin (the ultimate target of the Wnt signal transduction pathway that acts as a transcriptional co-activator of LEF/TCF proteins), and WDR77 (a transcriptional co-activator of multiple hormone receptors) are important for breast cellular transformation. Unexpectedly, these proteins interact directly with each other, and they have similar genomic binding profiles. Furthermore, while some of these common target sites coincide with those bound by LEF/TCF, the majority are located just downstream of transcription initiation sites at a position near paused RNA polymerase (Pol II) and the +1 nucleosome. Occupancy levels of these factors at these promoter-proximal sites are strongly correlated with the level of paused Pol II and transcriptional activity.
Antimicrobial activities of different solvent extracts from stem and seeds of Peganum Harmala L
Authors: Arif Muhammad , Wang Xiukang , Kazi Mohammad Sayyar Khan , Ullah Khan Shahid , Saeed Sumbul , Khan Amir Muhammad , Khan Rahmat Ali , Afzal Masood , Nawaz Ayesha Fazal , Zia Muhammad Amir , O. Elansary Hosam , Shokralla Shadi , Alhalabi Abdullah , Gul Alia , Fiaz Sajid
Published: April 2022

Wild medicinal herbs have been used as folk and traditional medicines all across the world since well before recorded history. This present study was designed to test the antimicrobial activities of five different solvent extracted samples (n-hexane, n-butanol, ethyl acetate, methanol, and water) of Peganum harmala using stems and seeds. Two different strains of Gram-negative bacteria (Escherichia coli and Klebsiella pneumonia), two Gram-positive bacteria (Bacillus subtilus and Staphylococcus aureus), and one fungal strain (Candida albicans) were used. The antimicrobial activities were measured using a disc diffusion assay. Two concentrations of the extracts (1 and 2mgDisc-1) were used. Ethyl acetate fraction was found more affective among the tested solvents and showed maximum activity (zone of inhibition) against S. aureus (65.53 and 81.10%), E. coli (46.22 and 61.29%) while n-butanol and water fractions gave maximum activity against S. aureus (78.86 and 70.00%) and K. pneumonia (57.00 and 61.39%) respectively. Water fraction showed maximum activity against C. albicans (60.00 and 81.88%). In the case of the stem, Ethyl acetate again showed more activity against B. subtilus (38.57 and 42.10%) and S. aureus (36.66 and 46.66%) while n-butanol showed maximum activity against K. pneumonia (24.55 and 32.44%) and E. coli (27.93 and 37.61%). Methanol was found more effective against C. albicans (25.71 and 43.80%). Seed extracted samples were found more effective compared to the stem. Ethyl acetate, butanol, and aqueous extracted samples showed good activity against the tested microbes, so these fractions are recommended for study their mechanism of actions and isolation of bioactive metabolites responsible for antimicrobial activities. The P. harmala should be evaluated for their bioactive compounds to be used in future studies. Our objective is to provide the framework for future study on the roles of P. harmala as traditional medicines.
Seasonal variation influences flavonoid biosynthesis path and content, and antioxidant activity of metabolites in Tetrastigma hemsleyanum Diels & Gilg
Authors: Shi YanShou , Yang Li , Yu MinFen , Li ZhaoHui , Ke ZhiJun , Qian XiaoHua , Ruan Xiao , He LiPing , Wei Feng , Zhao YingXian , Wang Qiang
Published: April 2022

Environmental conditions contribute to plant growth and metabolism. This study aimed to determine a suitable environment and climate for large-scale artificial cultivation of an endangered plant, Tetrastigma hemsleyanum, by investigating the seasonal variations influencing the flavonoid biosynthetic selectivity and antioxidant activity of its major metabolites. Under conditions of precipitation (2.0~6.6 mm), temperature (17.5~24.1°C), humidity (67.3~80.2%), and sunshine duration (3.4~5.8 h) from April to May, the total flavonoid content in T. hemsleyanum reached higher levels between 281.3 and 392.8 μg/g. In the second half of April, the production selectivity (PS) of isoorientin (IsoO), orientin (Or), rutin (Rut), isoquercitin (IsoQ), kaempferol-3-O-rutinoside (Km3rut), astragalin (Ast), quercetin (Qu), apigenin (Ap), and kaempferol (Km) were 0.30, 0.06, 0.07, 0.07, 0.00, 0.04, 0.38, 0.05, and 0.03, respectively. Naringenin was dehydrogenated or hydroxylated to initiate two parallel reaction pathways for flavonoid biosynthesis in T. hemsleyanum: path I subsequently generated flavone derivatives including apigenin, luteolin, orientin, and isoorientin, and path II subsequently generated flavonol derivatives including Km, Qu, IsoQ, Rut, Ast, and Km3rut. The reaction selectivity of path II (RPSII) from January 1 to September 30 was considerably higher than that of path I (RPSI), except for March 16–31. In addition, either the content or antioxidant activity of three major metabolites in T. hemsleyanum followed the order of phenolic compounds > polysaccharides > sterols, and exhibited dynamic correlations with environmental factors. Naringenin favored hydroxylation and derived six flavonol compounds from January to September, and favored dehydrogenation and derived three flavone compounds from October to December. In most months of a year, Km preferentially favored hydroxylation rather than glucosylation.
Topic modeling revisited: New evidence on algorithm performance and quality metrics
Authors: Rüdiger Matthias , Antons David , Joshi Amol M. , Salge Torsten-Oliver
Published: April 2022

Topic modeling is a popular technique for exploring large document collections. It has proven useful for this task, but its application poses a number of challenges. First, the comparison of available algorithms is anything but simple, as researchers use many different datasets and criteria for their evaluation. A second challenge is the choice of a suitable metric for evaluating the calculated results. The metrics used so far provide a mixed picture, making it difficult to verify the accuracy of topic modeling outputs. Altogether, the choice of an appropriate algorithm and the evaluation of the results remain unresolved issues. Although many studies have reported promising performance by various topic models, prior research has not yet systematically investigated the validity of the outcomes in a comprehensive manner, that is, using more than a small number of the available algorithms and metrics. Consequently, our study has two main objectives. First, we compare all commonly used, non-application-specific topic modeling algorithms and assess their relative performance. The comparison is made against a known clustering and thus enables an unbiased evaluation of results. Our findings show a clear ranking of the algorithms in terms of accuracy. Secondly, we analyze the relationship between existing metrics and the known clustering, and thus objectively determine under what conditions these algorithms may be utilized effectively. This way, we enable readers to gain a deeper understanding of the performance of topic modeling techniques and the interplay of performance and evaluation metrics.
Use of WhatsApp messaging technology to strengthen obstetric referrals in the Greater Accra Region, Ghana: Findings from a feasibility study
Authors: Owen Medge D. , Ismail Hebah M. , Goodman David , Batakji Mariam , Kim Sung Min , Olufolabi Adeyemi , Srofenyoh Emmanuel K.
Published: April 2022

In Ghana, the high-risk obstetric referral system is inadequate. Delay is common and patients often arrive to receiving hospitals in compromised states. An effective referral system should include an adequately resourced referral hospital, communication across sectors, accountability, transport, monitoring capability and policy support, which are currently lacking. A pilot program was undertaken to facilitate communication between hospital staffs. Additionally, data was collected to better understand and characterize obstetric referrals in Accra. Thirteen institutions were selected based on referral volume to implement the use of pre-referral treatment guidelines and WhatsApp as a mobile technology communication platform (Platform). Participants included healthcare workers from 8 health centers, 4 district hospitals, the Greater Accra Regional Hospital (GARH), administrators, doctors from other tertiary hospitals in Accra and medical consultants abroad. Facilities were provided smartphones and guidelines on using WhatsApp for advice on patient care or referral. Data were collected on WhatsApp communications among participants (March-August 2017). During this period, 618 cases were posted on the Platform and users increased from 69 to 81. The median response time was 17 min, a receiving hospital was identified 511 (82.7%) times and pre-referral treatment was initiated in 341 (55.2%). Subsequently, data collected on 597 referrals to GARH (September-November 2017) included 319 (53.4%) from Platform and 278 (46.6%) from non-Platform hospitals. Of these, 515 (86.3%) were urgent referrals; the median (interquartile range) referral to arrival time was 293 (111–1887) minutes without variation by facility grouping. Taxis were utilized for transportation in 80.2%; however, referral time shortened when patients arrived by ambulance and with a midwife. Only 23.5% of urgent referrals arrived within two hours. This project demonstrates that WhatsApp can be used as a communication tool for high-risk obstetric referrals and highlights the need to continue to improve urban referral processes due to identified delays which may contribute to poor outcomes.
Appropriateness of high-priority criteria and safety of endoscopy procedures during the COVID-19 lockdown
Authors: Morales-Arraez Dalia , Hernández Anjara , Hernández-Bustabad Alberto , Amaral Carla , Reygosa Cristina , Nicolás-Pérez David , Gimeno-García Antonio Zebenzui , Hernández-Guerra Manuel
Published: April 2022

Background

During the coronavirus-19 disease (COVID-19) pandemic, gastroenterology guidelines recommended the suspension or reduction of non-urgent endoscopy. We aimed to assess the appropriateness and safety of endoscopic activity during the pandemic first wave lockdown using European Society of Gastrointestinal Endoscopy (ESGE) recommendations.

Methods

We identified scheduled patients from the onset of the lockdown in Spain since March 16, 2020) to April 14, 2020. Daily hospital COVID-19-related burden was also registered. A similar cohort from a period immediately before the lockdown was studied (pre-lockdown cohort) to compare appropriateness.

Results

454 endoscopy procedures were performed during the studied period, comprising a 49.7% reduction compared to the pre-lockdown cohort (n = 913). There was a significant increase in ESGE high-priority indications (62.1% vs. 45.6%, p<0.001) associated with an increase in relevant endoscopic findings (p = 0.006), advanced neoplasia/cancer (p = 0.004) and cancer detection rate (p = 0.010). There were no differences in the rate of admissions or infection among scheduled patients in the lockdown cohort. None of the staff members tested positive for COVID-19 in the 7 days after the adoption of protective measures.

Conclusion

A prioritized endoscopic activity is not associated with higher contagion after adopting protective measures. In addition, a triage of procedures that follow the ESGE criteria increases the rate of relevant endoscopic findings. These considerations may reduce the impact of the delays of diagnosis after the pandemic.
Comprehensive analysis of GSEC/miR-101-3p/SNX16/PAPOLG axis in hepatocellular carcinoma
Authors: Hu Shangshang , Zhang Jinyan , Guo Guoqing , Zhang Li , Dai Jing , Gao Yu
Published: April 2022

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies. A growing number of studies have shown that competitive endogenous RNA (ceRNA) regulatory networks might play important roles during HCC process. The present study aimed to identify a regulatory axis of the ceRNA network associated with the development of HCC. The roles of SNX16 and PAPOLG in HCC were comprehensively analyzed using bioinformatics tools. Subsequently, the “mRNA-miRNA-lncRNA” model was then used to predict the upstream miRNAs and lncRNAs of SNX16 and PAPOLG using the miRNet database, and the miRNAs with low expression and good prognosis in HCC and the lncRNAs with high expression and poor prognosis in HCC were screened by differential expression and survival analysis. Finally, the risk-prognosis models of ceRNA network axes were constructed by univariate and multifactorial Cox proportional risk analysis, and the immune correlations of ceRNA network axes were analyzed using the TIMER and GEPIA database. In this study, the relevant ceRNA network axis GSEC/miR-101-3p/SNX16/PAPOLG with HCC prognosis was constructed, in which GSEC, SNX16, and PAPOLG were highly expressed in HCC with poor prognosis, while miR-101-3p was lowly expressed in HCC with good prognosis. The risk-prognosis model predicted AUC of 0.691, 0.623, and 0.626 for patient survival at 1, 3, and 5 years, respectively. Immuno-infiltration analysis suggested that the GSEC/miR-101-3p/SNX16/PAPOLG axis might affect macrophage polarization. The GSEC/miR-101-3p/SNX16/PAPOLG axis of the ceRNA network axis might be an important factor associated with HCC prognosis and immune infiltration.
Non-canonical genomic driver mutations of urethane carcinogenesis
Authors: Li Siqi , Counter Christopher M.
Published: April 2022

The carcinogen urethane induces pulmonary tumors in mice initiated by an incredibly specific Q61L/R oncogenic mutation in the proto-oncogene Kras. Previous Whole-Exome Sequencing of urethane-induced tumors revealed a bias towards A➙T/G and G➙A substitutions. Subsequent ultra-sensitive Maximum-Depth Sequencing of Kras shortly after urethane exposure suggest a further refinement to CA➙CT/G substitutions. As C182AA➙C182T/GA substitutions in Kras result in Q61L/R mutations, the extreme bias of urethane towards these genomic driver mutations can be ascribed to the specificity of the carcinogen for CA➙CT/G substitutions. However, we previously found that changing rare codons to common in the Kras gene to increase protein expression shifted mutations in urethane-induced tumors away from Kras, or when detected in Kras, to G12D mutations that are usually rarely detected in such tumors. Moreover, the loss of p53 partially reversed this effect, generating tumors with either Q61L/R or G12D oncogenic Kras mutations, or no Kras mutations, presumably due to other genomic driver mutations. Determining the origin of these G12D and other unknown non-canonical genomic driver mutations would provide critical insight into the extreme bias of carcinogens for specific genomic driver mutations. We thus compared the types of Single Nucleotide Variations detected by previously performed Maximum-Depth Sequencing immediately after urethane exposure to the mutation signatures derived from Whole Exome Sequencing of urethane-induced tumors. This identified two types of non-canonical mutations. First, a V637E oncogenic mutation in the proto-oncogene Braf that conforms to the mutation signature of urethane, suggesting that the mutational bias of the carcinogen may account for this non-canonical mutation, similar to that for canonical Q61L/R mutations in Kras. Second, G12D and Q61H mutations in Kras that did not fit this mutation signature, and instead shared similarity with Single Nucleotide Variations detected by Maximum-Depth Sequencing from normal cells, suggesting that perhaps these mutations were pre-existing. We thus posit that when canonical Kras mutations are selected against that the carcinogen may instead promote the expansion of pre-existing genomic driver mutations, although admittedly we cannot rule out other mechanisms. Interrogating the mutation signatures of human lung cancers similarly identified KRAS genomic driver mutations that failed to match the mutation signature of the tumor. Thus, we also speculate that the selection for non-canonical genomic driver mutations during urethane carcinogenesis may reflect the process by which discordance between genomic driver mutations and mutational signatures arises in human cancers.
Convergent validity of the Autism Spectrum Disorder Mealtime Behavior Questionnaire (ASD-MBQ) for children with autism spectrum disorder
Authors: Nakaoka Kazuyo , Tanba Hiroyuki , Yuri Takuma , Tateyama Kiyomi , Kurasawa Shigeki
Published: April 2022

There was a growing interest in difficulties with eating as one of the most problematic symptoms in children with autism spectrum disorder (ASD). The purpose of this study is to examine the convergent validity of the Autism Spectrum Disorder Mealtime Behavior Questionnaire (ASD-MBQ) with the Asahide’s test for social adjustment skills, the Japanese version of the short version of the sensory profile questionnaire, the Japanese version of the Social Communication Questionnaire, and the Parenting Strain Index in Japanese children with ASD. The final sample contained 294 children who were diagnosed as the ASD based on the DSM-5 criteria, the mean age of children was 10 ± 4 years (range: 3–18 years). The ASD-MBQ is a questionnaire that comprised of 42 items that are classified into five subdomains: selective eating, clumsiness/manners, interest in/concentration on eating, oral-motor function, and overeating. Spearman’s rank correlation coefficient revealed that the ASD-MBQ showed the moderate to high correlation coefficient with all four external criteria. Our results in this study supported the sufficient convergent validity in the ASD-MBQ. Therefore, the ASD-MBQ could be a useful tool for research and practice in a wide range of children with ASD aged 3 to 18.
Normal embryonic development and neonatal digit regeneration in mice overexpressing a stem cell factor, Sall4
Authors: Chen Katherine Q. , Anderson Aaron , Kawakami Hiroko , Kim Jennifer , Barrett Janaya , Kawakami Yasuhiko
Published: April 2022

Sall4encodes a transcription factor and is known to participate in the pluripotency network of embryonic stem cells.Sall4expression is known to be high in early stage post-implantation mouse embryos. During early post-gastrulation stages,Sall4is highly expressed in the tail bud and distal limb buds, where progenitor cells are maintained in an undifferentiated status. The expression ofSall4is rapidly downregulated during embryonic development. We previously demonstrated thatSall4is required for limb and posterior axial skeleton development by conditional deletion ofSall4in theT(Brachyury) lineage. To gain insight intoSall4functions in embryonic development and postnatal digit regeneration, we genetically overexpressedSall4in the mesodermal lineage by theTCretransgene and a novel knockin allele ofRosa26-loxP-stop-loxP-Sall4. In significant contrast to severe defects bySall4loss of function reported in previous studies, overexpression ofSall4resulted in normal morphology and pattern in embryos and neonates. The length of limb long bones showed subtle reduction inSall4-overexpression mice. It is known that the digit tip of neonatal mice has level-specific regenerative ability after experimental amputation. We observedSall4expression in the digit tip by using a sensitiveSall4-LacZknock-in reporter expression.Sall4overexpression did not alter the regenerative ability of the terminal phalange that normally regenerates after amputation. Moreover,Sall4overexpression did not confer regenerative ability to the second phalange that normally does not regenerate after amputation. These genetic experiments show that overexpression ofSall4does not alter the development of the appendicular and axial skeleton, or neonatal digit regeneration. The results suggest thatSall4acts as a permissive factor rather than playing an instructive role.
A community intervention effectiveness study of single dose or two doses of bivalent HPV vaccine (CERVARIX®) in female school students in Thailand
Authors: Jiamsiri Suchada , Rhee Chulwoo , Ahn Hyeon Seon , Poudyal Nimesh , Seo Hyeong-Won , Klinsupa Worrawan , Nilyanimit Pornjarim , Premsri Nakorn , Namwat Chawetsan , Vonpunsawad Sompong , Chon Yun , Park Sunju , Kim Deok-Ryun , Unger Elizabeth R. , Markowitz Lauri , Poovorawan Yong , Rerks-Ngarm Supachai , Excler Jean Louis , Lynch Julia
Published: April 2022

Human papillomavirus (HPV) is a common infection principally spread through sexual activity. Most HPV infections are asymptomatic and resolve spontaneously. However, persistent infection may progress to cervical cancer. Highly efficacious HPV vaccines have been available since 2006, yet uptake into national programs has been slow in part due to cost. WHO guidelines call for a two-dose (0,6 month) schedule for girls 9–14 years of age. Post-hoc analyses of randomized trials have found high vaccine effectiveness following a single dose of vaccine. In order to provide additional data on the potential impact of single dose HPV vaccination in a real-world setting, we are conducting an effectiveness study among Thai schoolgirls. This is an observational study of a single dose (SD) or two doses (2D) of the bivalent HPV vaccine CERVARIX® (GlaxoSmithKline plc.) administered in a school-based program to 8–9,000 Grade 8 female students in two provinces of Thailand beginning in 2018; one province is assigned the SD, and the other the standard 2D regimen. The reduction in HPV vaccine-type prevalence will be assessed in each province two and four years after vaccination by comparing HPV prevalence in urine samples obtained through cross-sectional surveys of the immunized grade cohort as they age and compared to a historical “baseline” HPV prevalence of same age students.
Bioactivity study and metabolic profiling of Colletotrichum alatae LCS1, an endophyte of club moss Lycopodium clavatum L.
Authors: Santra Hiran Kanti , Banerjee Debdulal
Published: April 2022

Endophytes are silent microbial partners of green plants that ensure hosts’ survival in odd conditions. They are known as the factories of multipotent metabolites with diverse bioactivities beneficial to modern pharmaceuticals industry. Endophytic fungi have been screened from a variety of plants and it is the first-time endophytes of club moss is being studied for production of antibacterial and antioxidative compounds. The present study reveals that Lycopodium clavatum L. harbors a potent niche of bioactive endophytic fungi and Colletotrichum alatae LCS1 was the prime producer of antibacterial and antioxidative compounds among them. The minimum inhibitory and bactericidal concentrations of ethyl- acetate culture extract ranged from 15.62 to 250 μg/mL against four Gram negative and three Gram positive microorganisms including methicillin resistant Staphylococcus aureus (ATCC-33591). Bio-autogram based screening followed by Gas chromatographic analysis confirmed the occurrence of 17 bioactive compounds and α-bisabolol is known to be the prime one. Alfa bisabolol is a unique and versatile bioactive essential oil and facilitates variety of functions. Killing kinetics data along with leakage of macromolecules into extracellular environment supports the cidal activity of the antibacterial principles at MBC values. Isolate C. alatae LCS1 was optimized by one variable at a time system coupled with response surface methodology for broad spectrum antibacterial production. The organism yielded maximum response (22.66±0.894 mm of zone of inhibition against MRSA) in 250 mL Erlenmeyer flask containing 50 mL potato dextrose broth supplemented with (g/L) glucose, 7.53; yeast extract concentration, 0.47; NaCl, 0.10 with medium pH 6.46; after 134 hours of incubation at 26°C. Optimized fermentation parameters enhanced antibacterial activity up-to more than 50% than the pre-optimized one (10.33±0.57 mm). Endophytic LCS1 was also efficient in free radical scavenging tested by DPPH, ABTS, H2O2 and FRAP assay with an IC50 values of 23.38±5.32 to 82.873±6.479 μg/mL.
Pixel-based versus object-based identification of scenic resources using Gaofen-2 images: A case study of Yesanpo National Park
Authors: Jia Zhe , Qin Anchen
Published: April 2022

Scenic resources can serve as symbols of a region’s natural resources and culture and are often the stimulus for the development of national parks. Thus, careful scientific planning and effective management based on the identification and evaluation of scenic resources are key for the sustainable development of national parks. In this study, one object-oriented and three pixel-based (maximum likelihood classification, neural network, and support vector machine) classification methods were applied to identify scenic resources in Yesanpo National Park using high-resolution Gaofen-2 images. The classification accuracy of these scenic resources was evaluated through systematic sampling, which improved the objectivity and accuracy of the classification precision evaluation. All methods met the precision requirements of scenic resource identification, and the accuracy of object-oriented classification was the highest. The application scope of the different methods varies, and suitability can be determined according to the needs of scenic resource recognition. Collectively, this study has proposed an effective and practical method for the identification of scenic resources within Yesanpo National Park, which is of significance for its future planning and management. Moreover, this strategy can be applied by other national park planners to select areas for tourism development, formulate sustainable development strategies, and provide technical support and decision-making guidance for national park planning and management.
Bioactive adrenomedullin in sepsis patients in the emergency department is associated with mortality, organ failure and admission to intensive care
Authors: Lundberg Oscar H. M. , Rosenqvist Mari , Bronton Kevin , Schulte Janin , Friberg Hans , Melander Olle
Published: April 2022

Background

Adrenomedullin is a vasoactive hormone with potentially prognostic and therapeutic value, which mainly has been investigated in intensive care unit (ICU) settings. The triaging in the emergency department (ED) of patients to the right level of care is crucial for patient outcome.

Objectives

The primary aim of this study was to investigate the association of bioactive adrenomedullin (bio-ADM) with mortality among sepsis patients in the ED. Secondary aims were to investigate the association of bio-ADM with multiple organ failure (MOF), ICU admission and ED discharge.

Methods

In this prospective observational cohort study, adult sepsis patients in the ED (2013–2015) had blood samples collected for later batch analysis of bio-ADM. Odds ratios (OR) with 95% confidence interval (CI) for bio-ADM were calculated.

Results

Bio-ADM in 594 sepsis patients was analyzed of whom 51 died within 28 days (8.6%), 34 developed severe MOF, 27 were ICU admitted and 67 were discharged from the ED. The median (interquartile range) bio-ADM was 36 (26–56) and 63 (42–132) pg/mL among survivors and non-survivors, respectively, 81 (56–156) pg/mL for patients with severe MOF and 77 (42–133) pg/mL for ICU admitted patients. Each log-2 increment of bio-ADM conferred an OR of 2.30 (95% CI 1.74–3.04) for mortality, the adjusted OR was 2.39 (95% CI 1.69–3.39). The area under the receiver operating characteristic curve of a prognostic mortality model based on demographics and biomarkers increased from 0.80 to 0.86 (p = 0.02) when bio-ADM was added. Increasing bio-ADM was associated with severe MOF, ICU admission and ED discharge with adjusted ORs of 3.30 (95% CI 2.13–5.11), 1.75 (95% CI 1.11–2.77) and 0.46 (95% CI 0.32–0.68), respectively.

Conclusion

Bio-ADM in sepsis patients in the ED is associated with mortality, severe MOF, ICU admission and ED discharge, and may be of clinical importance for triage of sepsis patients in the ED.
Instant classification for the spatially-coded BCI
Authors: Maÿe Alexander , Rauterberg Raika , Engel Andreas K.
Published: April 2022

The spatially-coded SSVEP BCI exploits changes in the topography of the steady-state visual evoked response to visual flicker stimulation in the extrafoveal field of view. In contrast to frequency-coded SSVEP BCIs, the operator does not gaze into any flickering lights; therefore, this paradigm can reduce visual fatigue. Other advantages include high classification accuracies and a simplified stimulation setup. Previous studies of the paradigm used stimulation intervals of a fixed duration. For frequency-coded SSVEP BCIs, it has been shown that dynamically adjusting the trial duration can increase the system’s information transfer rate (ITR). We therefore investigated whether a similar increase could be achieved for spatially-coded BCIs by applying dynamic stopping methods. To this end we introduced a new stopping criterion which combines the likelihood of the classification result and its stability across larger data windows. Whereas the BCI achieved an average ITR of 28.4±6.4 bits/min with fixed intervals, dynamic intervals increased the performance to 81.1±44.4 bits/min. Users were able to maintain performance up to 60 minutes of continuous operation. We suggest that the dynamic response time might have worked as a kind of temporal feedback which allowed operators to optimize their brain signals and compensate fatigue.
Sharing, reuse, and storage of biosamples among biomedical researchers in Jordan: Practice and concerns
Authors: Alkaraki Almuthanna K. , Khabour Omar F. , Alzoubi Karem H. , Al-Ebbini Lina M. K. , Altaany Zaid
Published: April 2022

Background

Sharing and reuse biosamples can facilitate biomedical research. Little is known about researchers’ perception and practice about sharing, reusing, and storing biosamples in Jordan. Therefore, the current study aimed to evaluate the practices of biomedical researchers in Jordan regarding biosamples management.

Methods

The study was cross-sectional and involved biomedical researchers from different parts of Jordan. A questionnaire was designed to achieve the aim of this study. The questionnaire was web-based and distributed via e-mails using Google forms.

Results

Opinions of Jordanian biomedical researchers from different academic ranks and institutional backgrounds were measured and recorded anonymously. The majority of the sample was males (57.9%), from public universities (64.3%), and (64.6%) were from health-related fields. About 82.9% of participants stored biosamples using codes, whereas the rest used the subject’s name. Sharing of biosamples was commonly practiced by 61.7% of Jordanian researchers locally, while 47.2% of the Jordanian researchers shared biosamples overseas. The reuse of biosamples in other projects was reported to be 55.4%. The majority explained the possibility of reusing and sharing biosamples in the consent form (range: 53–58%). Sharing and reusing biosamples were associated with gender, the number of publications in peer-reviewed international journals, and academic rank (P<0.05).

Conclusion

Sharing and reusing biosamples are common among Jordanian biomedical researchers. Therefore, ethically grounded biosamples sharing and reuse standards are essential for protecting human subjects’ rights and privacy in Jordan.