bluuebunny/crossref_metadata_2025 huggingface dataset:
Personalized Pollen Monitoring and Symptom Scores: A Feasibility Study in Grass Pollen Allergic Patients
Authors: de Weger Letty A. , van Hal Peter Th. W. , Bos Bernadette , Molster Frank , Mostert Marijke , Hiemstra Pieter S.
Published: April 2021

Background: Pollen is a major trigger for allergic symptoms in sensitized individuals. Airborne pollen is usually monitored by Hirst type pollen samplers located at rooftop level, providing a general overview of the pollen distribution in the larger surroundings. In this feasibility study, grass pollen-sensitized subjects monitored the pollen in their direct environment using a portable pollen sampler (Pollensniffer) and scored their symptoms, to study the relation between symptom severity and personal grass pollen exposure. For comparison the symptoms were also correlated with pollen collected by the rooftop sampler.

Methods: After recruitment 18 participants were screened for grass pollen specific (GP-sIgE) of which 12 were eligible. Nine participants completed the study (May, 2018). They were asked to monitor personal pollen exposure using a Pollensniffer on their way to school, work or other destination, and to score their symptoms via a mobile app on a scale from 0 to 10. Daily pollen concentrations were collected by a Hirst type sampler at rooftop level. Pollen grains were analyzed using a microscope.

Results: Three of the four participants with high GP-sIgE (≥9.6 kU/l) reported high symptom scores (>4) and an analysis showed a significant correlation (CC) between eye, nose, and lung symptoms and the grass pollen counts collected by the Pollensniffer, as well as the daily grass pollen concentrations monitored by the rooftop sampler (CC≥0.54). In contrast, the participants with low GP-sIgE levels (<9.6 kU/l) reported low symptom scores (≤4) and often other sensitizations were present. For these subjects, no significant positive correlations (CC<0.3) of symptoms with either grass pollen collected by the personal or the rooftop sampler were found.

Conclusion: The results of this feasibility study suggest that correlations between the severity of clinical symptoms of grass pollen allergic patients, and grass pollen counts as determined by the Pollensniffer or a rooftop sampler, is restricted to patients with high GP-sIgE levels, high symptom scores, and no relevant other sensitizations. Based on the low numbers of subjects with severe symptoms included in this feasibility study, no conclusions can be drawn on the performance of the Pollensniffer in relating symptoms and pollen exposure in comparison with the rooftop sampler.

Trial Registration: The study was approved by the Committee Medical Ethics of the LUMC (approval numbers: NL63953.058.17/ P17.304).
Tension Estimation Method for Cable With Damper Using Natural Frequencies
Authors: Furukawa Aiko , Hirose Katsuya , Kobayashi Ryosuke
Published: April 2021

In the maintenance of cable structures, such as cable-stayed bridges and extra-dosed bridges, it is necessary to estimate the tension acting on the cables. The safety of a cable is confirmed by checking whether the tension acting on the cable is within the allowable value. In current Japanese practice, the tension of a cable is estimated using the vibration method or the higher-order vibration method, which considers the natural frequencies of the cable. However, in recent years, the aerodynamic vibration of cables caused by wind has become a problem owing to the recent increase in the cable length and low damping performance of the cable itself. To suppress the aerodynamic vibration of cables, dampers are installed onto the cables. Because the damper changes the cable’s natural frequencies, the vibration method and higher-order vibration method are inappropriate for measuring the tension of a cable with a damper. In this paper, a new tension estimation method for a cable with a damper is proposed. To model a cable with a tensioned Bernoulli-Euler beam, theoretical equations for estimating the natural frequencies were derived. The proposed method inversely estimates the tension and bending stiffness of the cable and damper parameters, simultaneously, from the natural frequencies. The validity of the proposed method was confirmed by conducting numerical simulations and experiments. In the numerical verification, the performance of the proposed method was investigated using 80 numerical models. In the experimental verification, the estimation accuracy of the proposed method was investigated by considering 16 test cases. Thus, it was confirmed that the tension estimation accuracy was high, whereas the bending stiffness and damper parameter estimation accuracy was unsatisfactory. The tension estimation error was within 10% in all experimental cases, and within 5% if two test cases are excluded. The results obtained by the numerical and experimental verifications confirmed the effectiveness of the proposed method in tension estimation.
Transgelin-2: A Double-Edged Sword in Immunity and Cancer Metastasis
Authors: Kim Hye-Ran , Park Jeong-Su , Karabulut Hatice , Yasmin Fatima , Jun Chang-Duk
Published: April 2021

Transgelin-2, a small actin-binding protein, is the only transgelin family member expressed in immune cells. In T and B lymphocytes, transgelin-2 is constitutively expressed, but in antigen-presenting cells, it is significantly upregulated upon lipopolysaccharide stimulation. Transgelin-2 acts as a molecular staple to stabilize the actin cytoskeleton, and it competes with cofilin to bind filamentous (F)-actin. This action may enable immune synapse stabilization during T-cell interaction with cognate antigen-presenting cells. Furthermore, transgelin-2 blocks Arp2/3 complex-nucleated actin branching, which is presumably related to small filopodia formation, enhanced phagocytic function, and antigen presentation. Overall, transgelin-2 is an essential part of the molecular armament required for host defense against neoplasms and infectious diseases. However, transgelin-2 acts as a double-edged sword, as its expression is also essential for a wide range of tumor development, including drug resistance and metastasis. Thus, targeting transgelin-2 can also have a therapeutic advantage for cancer treatment; selectively suppressing transgelin-2 expression may prevent multidrug resistance in cancer chemotherapy. Here, we review newly discovered molecular characteristics of transgelin-2 and discuss clinical applications for cancer and immunotherapy.
Selective Requirements for Vascular Endothelial Cells and Circulating Factors in the Regulation of Retinal Neurogenesis
Authors: Dhakal Susov , Rotem-Bamberger Shahar , Sejd Josilyn R. , Sebbagh Meyrav , Ronin Nathan , Frey Ruth A. , Beitsch Mya , Batty Megan , Taler Kineret , Blackerby Jennifer F. , Inbal Adi , Stenkamp Deborah L.
Published: April 2021

Development of the vertebrate eye requires signaling interactions between neural and non-neural tissues. Interactions between components of the vascular system and the developing neural retina have been difficult to decipher, however, due to the challenges of untangling these interactions from the roles of the vasculature in gas exchange. Here we use the embryonic zebrafish, which is not yet reliant upon hemoglobin-mediated oxygen transport, together with genetic strategies for (1) temporally-selective depletion of vascular endothelial cells, (2) elimination of blood flow through the circulation, and (3) elimination of cells of the erythroid lineage, including erythrocytes. The retinal phenotypes in these genetic systems were not identical, with endothelial cell-depleted retinas displaying laminar disorganization, cell death, reduced proliferation, and reduced cell differentiation. In contrast, the lack of blood flow resulted in a milder retinal phenotype showing reduced proliferation and reduced cell differentiation, indicating that an endothelial cell-derived factor(s) is/are required for laminar organization and cell survival. The lack of erythrocytes did not result in an obvious retinal phenotype, confirming that defects in retinal development that result from vascular manipulations are not due to poor gas exchange. These findings underscore the importance of the cardiovascular system supporting and controlling retinal development in ways other than supplying oxygen. In addition, these findings identify a key developmental window for these interactions and point to distinct functions for vascular endothelial cells vs. circulating factors.
AFP-Inhibiting Fragments for Drug Delivery: The Promise and Challenges of Targeting Therapeutics to Cancers
Authors: Lin Bo , Dong Xu , Wang Qiujiao , Li Wei , Zhu Mingyue , Li Mengsen
Published: April 2021

Alpha fetoprotein (AFP) plays a key role in stimulating the growth, metastasis and drug resistance of hepatocellular carcinoma (HCC). AFP is an important target molecule in the treatment of HCC. The application of AFP-derived peptides, AFP fragments and recombinant AFP (AFP-inhibiting fragments, AIFs) to inhibit the binding of AFP to intracellular proteins or its receptors is the basis of a new strategy for the treatment of HCC and other cancers. In addition, AIFs can be combined with drugs and delivery agents to target treatments to cancer. AIFs conjugated to anticancer drugs not only destroy cancer cells with these drugs but also activate immune cells to kill cancer cells. Furthermore, AIF delivery of drugs relieves immunosuppression and enhances chemotherapy effects. The synergism of immunotherapy and targeted chemotherapy is expected to play an important role in enhancing the treatment effect of patients with cancer. AIF delivery of drugs will be an available strategy for the targeted treatment of cancer in the future.
Targeting TFE3 Protects Against Lysosomal Malfunction-Induced Pyroptosis in Random Skin Flaps via ROS Elimination
Authors: Li Jiafeng , Lou Junsheng , Yu Gaoxiang , Chen Yijie , Chen Ruiheng , Chen Zhuliu , Wu Chenyu , Ding Jian , Xu Yu , Jiang Jingtao , Xu Huazi , Zhu Xuwei , Gao Weiyang , Zhou Kailiang
Published: April 2021

Increasing evidence indicates that pyroptosis, a new type of programmed cell death, may participate in random flap necrosis and play an important role. ROS-induced lysosome malfunction is an important inducement of pyroptosis. Transcription factor E3 (TFE3) exerts a decisive effect in oxidative metabolism and lysosomal homeostasis. We explored the effect of pyroptosis in random flap necrosis and discussed the effect of TFE3 in modulating pyroptosis. Histological analysis via hematoxylin-eosin staining, immunohistochemistry, general evaluation of flaps, evaluation of tissue edema, and laser Doppler blood flow were employed to determine the survival of the skin flaps. Western blotting, immunofluorescence, and enzyme-linked immunosorbent assays were used to calculate the expressions of pyroptosis, oxidative stress, lysosome function, and the AMPK-MCOLN1 signaling pathway. In cell experiments, HUVEC cells were utilized to ensure the relationship between TFE3, reactive oxygen species (ROS)-induced lysosome malfunction and cell pyroptosis. Our results indicate that pyroptosis exists in the random skin flap model and oxygen and glucose deprivation/reperfusion cell model. In addition, NLRP3-mediated pyroptosis leads to necrosis of the flaps. Moreover, we also found that ischemic flaps can augment the accumulation of ROS, thereby inducing lysosomal malfunction and finally initiating pyroptosis. Meanwhile, we observed that TFE3 levels are interrelated with ROS levels, and overexpression and low expression of TFE3 levels can, respectively, inhibit and promote ROS-induced lysosomal dysfunction and pyroptosis during in vivo and in vitro experiments. In conclusion, we found the activation of TFE3 in random flaps is partially regulated by the AMPK-MCOLN1 signal pathway. Taken together, TFE3 is a key regulator of ROS-induced pyroptosis in random skin flaps, and TFE3 may be a promising therapeutic target for improving random flap survival.
Prenatal Development and Function of Human Mononuclear Phagocytes
Authors: Miah Mohi , Goh Issac , Haniffa Muzlifah
Published: April 2021

The human mononuclear phagocyte (MP) system, which includes dendritic cells, monocytes, and macrophages, is a critical regulator of innate and adaptive immune responses. During embryonic development, MPs derive sequentially in yolk sac progenitors, fetal liver, and bone marrow haematopoietic stem cells. MPs maintain tissue homeostasis and confer protective immunity in post-natal life. Recent evidence – primarily in animal models – highlight their critical role in coordinating the remodeling, maturation, and repair of target organs during embryonic and fetal development. However, the molecular regulation governing chemotaxis, homeostasis, and functional diversification of resident MP cells in their respective organ systems during development remains elusive. In this review, we summarize the current understanding of the development and functional contribution of tissue MPs during human organ development and morphogenesis and its relevance to regenerative medicine. We outline how single-cell multi-omic approaches and next-generationex-vivoorgan-on-chip models provide new experimental platforms to study the role of human MPs during development and disease.
Inhibition by Thyroid Hormones of Cell Migration Activated by IGF-1 and MCP-1 in THP-1 Monocytes: Focus on Signal Transduction Events Proximal to Integrin αvβ3
Authors: Candelotti Elena , De Luca Roberto , Megna Roberto , Maiolo Mariangela , De Vito Paolo , Gionfra Fabio , Percario Zulema Antonia , Borgatti Monica , Gambari Roberto , Davis Paul J. , Lin Hung-Yun , Polticelli Fabio , Persichini Tiziana , Colasanti Marco , Affabris Elisabetta , Pedersen Jens Z. , Incerpi Sandra
Published: April 2021

Interaction between thyroid hormones and the immune system is reported in the literature. Thyroid hormones, thyroxine, T4, but also T3, act non-genomically through mechanisms that involve a plasma membrane receptor αvβ3 integrin, a co-receptor for insulin-like growth factor-1 (IGF-1). Previous data from our laboratory show a crosstalk between thyroid hormones and IGF-1 because thyroid hormones inhibit the IGF-1-stimulated glucose uptake and cell proliferation in L-6 myoblasts, and the effects are mediated by integrin αvβ3. IGF-1 also behaves as a chemokine, being an important factor for tissue regeneration after damage. In the present study, using THP-1 human leukemic monocytes, expressing αvβ3 integrin in their cell membrane, we focused on the crosstalk between thyroid hormones and either IGF-1 or monocyte chemoattractant protein-1 (MCP-1), studying cell migration and proliferation stimulated by the two chemokines, and the role of αvβ3 integrin, using inhibitors of αvβ3 integrin and downstream pathways. Our results show that IGF-1 is a potent chemoattractant in THP-1 monocytes, stimulating cell migration, and thyroid hormone inhibits the effect through αvβ3 integrin. Thyroid hormone also inhibits IGF-1-stimulated cell proliferation through αvβ3 integrin, an example of a crosstalk between genomic and non-genomic effects. We also studied the effects of thyroid hormone on cell migration and proliferation induced by MCP-1, together with the pathways involved, by a pharmacological approach and docking simulation. Our findings show a different downstream signaling for IGF-1 and MCP-1 in THP-1 monocytes mediated by the plasma membrane receptor of thyroid hormones, integrin αvβ3.
Molecular Dynamics Simulations on Influence of Defect on Thermal Conductivity of Silicon Nanowires
Authors: Li Hao , Rui Qiancheng , Wang Xiwen , Yu Wei
Published: April 2021

A non-equilibrium molecular dynamics simulation method is conducted to study the thermal conductivity (TC) of silicon nanowires (SiNWs) with different types of defects. The impacts of defect position, porosity, temperature, and length on the TC of SiNWs are analyzed. The numerical results indicate that SiNWs with surface defects have higher TC than SiNWs with inner defects, the TC of SiNWs gradually decreases with the increase of porosity and temperature, and the impact of temperature on the TC of SiNWs with defects is weaker than the impact on the TC of SiNWs with no defects. The TC of SiNWs increases as their length increases. SiNWs with no defects have the highest corresponding frequency of low-frequency peaks of phonon density of states; however, when SiNWs have inner defects, the lowest frequency is observed. Under the same porosity, the average phonon participation of SiNWs with surface defects is higher than that of SiNWs with inner defects.
The Benefits and Limits of Urban Tree Planting for Environmental and Human Health
Authors: Pataki Diane E. , Alberti Marina , Cadenasso Mary L. , Felson Alexander J. , McDonnell Mark J. , Pincetl Stephanie , Pouyat Richard V. , Setälä Heikki , Whitlow Thomas H.
Published: April 2021

Many of the world’s major cities have implemented tree planting programs based on assumed environmental and social benefits of urban forests. Recent studies have increasingly tested these assumptions and provide empirical evidence for the contributions of tree planting programs, as well as their feasibility and limits, for solving or mitigating urban environmental and social issues. We propose that current evidence supports local cooling, stormwater absorption, and health benefits of urban trees for local residents. However, the potential for urban trees to appreciably mitigate greenhouse gas emissions and air pollution over a wide array of sites and environmental conditions is limited. Consequently, urban trees appear to be more promising for climate and pollutionadaptationstrategies than mitigation strategies. In large part, this is due to space constraints limiting the extent of urban tree canopies relative to the current magnitude of emissions. The most promising environmental and health impacts of urban trees are those that can be realized with well-stewarded tree planting and localized design interventions at site to municipal scales. Tree planting at these scales has documented benefits on local climate and health, which can be maximized through targeted site design followed by monitoring, adaptive management, and studies of long-term eco-evolutionary dynamics.
The Challenge of Ambient Air–Processed Organometallic Halide Perovskite: Technology Transfer From Spin Coating to Meniscus Blade Coating of Perovskite Thin Films
Authors: Fong Patrick Wai-Keung , Li Gang
Published: April 2021

The development of perovskite solar cells (PSCs) has been extensively studied in the past decade, and the power conversion efficiency (PCE) has reached a record of 25.2%. Despite impressively high PCE, the fabrication process mainly relied on a well-controlled environment, an inert gas–filled glovebox, and devices of small areas were demonstrated. This impedes the technology transfer from laboratory scale spin coating to manufacturing ambient air scalable processes. Furthermore, the nucleation and crystal growth processes of the perovskite thin films are different when the films are prepared in different environmental conditions. In this review, we summarize the recent advances of ambient air–processed organometallic halide perovskite thin films. Focuses are made on the impact of ambient air conditions, typically adventitious moisture, on the crystallization of perovskites thin films. The challenges and strategies in the technology transfer from the glovebox or ambient air spin coating to scalable meniscus blade coating are also discussed to shed light on the manufacture of ambient air–processed PSCs.
Real-World Ethical Dilemmas in Laboratory Safety for Microbiology Under-Resourced and Outreach Teaching
Authors: Smith-Keiling Beverly L.
Published: April 2021

With modernization of safety standards for microbiology outreach teaching laboratories, ethical challenges arise in teaching microbiology for the public good without short-changing students in under-resourced situations, or when institutional support is subpar. Still, educators want students to engage using applied skills for inquiry, research-based microbial learning activities – safely. Following several United States microbial outbreaks, federal investigation traced sources back to teaching laboratories. Policy discussions ensued. The American Society for Microbiology (ASM) Task Force provides recommended but not mandated guidelines; however, guidelines are not amenable by all. Here, a real-world, ethical scenario of a university-level outreach microbiology laboratory course hosted at several locations provides context for under-resourced challenges in safety compliance. In this example of biomedical and public health ethical considerations, upper administration puts the onus on instructors to assure safe labs for their students and the general public. Temporarily hired instructors without curriculum or sufficient institutional support are put in precarious positions with often egregious practices to get the job done. This scenario is examined with different public health ethical frameworks and principles: non-maleficence, beneficence, health maximization, efficiency of policy regulations, respect for institutional and instructor autonomy, justice, and proportionality balancing stakeholder concerns. Sample curricular strategies are employed to mitigate these challenges. Taking a utilitarianism framework of the greatest good for the most benefit, this paper advocates for social justice supporting access to education as a moral duty. Administrations should ensure instructors are supported sufficiently to provide safe, authentic learning experiences. Solutions for under-resourced outreach teaching are needed for public trust.
Do Long-Term Conservation Pasture Management Practices Influence Microbial Diversity and Antimicrobial Resistant Genes in Runoff?
Authors: Yang Yichao , Ashworth Amanda J. , Durso Lisa M. , Savin Mary , DeBruyn Jennifer M. , Cook Kimberly , Moore Philip A. , Owens Phillip R.
Published: April 2021

Runoff from land-applied manure and poultry litter is one mechanism by which manure-borne bacteria are transported over large distances in the environment. There is a global concern that antimicrobial resistant (AMR) genes may be transmitted through the food chain from animal manures to soil to surface water. However, details are lacking on the ecology of AMR genes in water runoff as well as how conservation management practices may affect the runoff microbiome or minimize the movement of AMR genes. The aim of this study was to identify microbial community structure and diversity in water runoff following 14-years of poultry litter and cattle manure deposition and to evaluate the amount of AMR genes under five conventional and conservation pasture management strategies. Since 2004, all watersheds received annual poultry litter at a rate of 5.6 Mg ha−1 and were consistently managed. Surface runoff samples were collected from each watershed from 2018 to 2019, characterized using Illumina 16S rRNA gene amplicon sequencing and enumerated for four AMR-associated genes (ermB, sulI, intlI, and blactx-m-32) using quantitative PCR. Overall, long-term pasture management influenced water microbial community structure, with effects differing by year (p < 0.05). Bacterial richness (Chao1 index) was influenced by pasture management, with the lowest richness occurring in the control (nearby non-agricultural water source) and the greatest under fields that were hayed (no cattle presence). Runoff bacterial richness in watersheds increased following poultry litter applications, indicating poultry litter is a possible source of bacteria and altered runoff community structure. The blactx-m-32 gene was not detected in any surface water sample. The remaining three AMR genes were absent in the non-agricultural control, but present in agricultural samples. However, there was no impact (p > 0.05) from pasture management on the abundance of these genes, indicating both conventional and conservation practices have similar ecologies for these targets; however, there was a greater detection of sulI genes from runoff in continuously grazed systems in 2019, with hay being lowest in 2019. Results illustrate that the edge of field buffer strips may increase bacterial richness in water runoff, but these changes in richness do not greatly impact target AMR genes in the United States largest land-use category.
Phosphorus Release and Regeneration Following Laboratory Lysis of Bacterial Cells
Authors: Mine Aric H. , Coleman Maureen L. , Colman Albert S.
Published: April 2021

The availability of phosphorus limits primary production in large regions of the oceans, and marine microbes use a variety of strategies to overcome this limitation. One strategy is the production of alkaline phosphatase (APase), which allows hydrolysis of larger dissolved organic phosphorus (DOP) compounds in the periplasm or at the cell surface for transport of orthophosphate into the cell. Cell lysis, driven by grazing and viral infection, releases phosphorus-containing cell components, along with active enzymes that could persist after lysis. The importance of this continued enzymatic activity for orthophosphate regeneration is unknown. We used three model bacteria – Escherichia coli K-12 MG1655, Synechococcus sp. WH7803, and Prochlorococcus sp. MED4 – to assess the impact of continued APase activity after cell lysis, via lysozyme treatment, on orthophosphate regeneration. Direct release of orthophosphate scaled with cell size and was reduced under phosphate-starved conditions where APase activity continued for days after lysis. All lysate incubations showed post-lysis orthophosphate generation suggesting phosphatases other than APase maintain activity. Rates of DOP hydrolysis and orthophosphate remineralization varied post-lysis among strains. Escherichia coli K-12 MG1655 rates of remineralization were 0.6 and 1.2 amol cell–1hr–1 under deplete and replete conditions; Synechococcus WH7803 lysates ranged from 0.04 up to 0.3 amol cell–1hr–1 during phosphorus deplete and replete conditions, respectively, while in Prochlorococcus MED4 lysates, rates were stable at 0.001 amol cell–1hr–1 in both conditions. The range of rates of hydrolysis and regeneration underscores the taxonomic and biochemical variability in the process of nutrient regeneration and further highlights the complexity of quantitatively resolving the major fluxes within the microbial loop.
Virulence Factors in Hypervirulent Klebsiella pneumoniae
Authors: Zhu Jie , Wang Tao , Chen Liang , Du Hong
Published: April 2021

Hypervirulent Klebsiella pneumoniae (hvKP) has spread globally since first described in the Asian Pacific Rim. It is an invasive variant that differs from the classical K. pneumoniae (cKP), with hypermucoviscosity and hypervirulence, causing community-acquired infections, including pyogenic liver abscess, pneumonia, meningitis, and endophthalmitis. It utilizes a battery of virulence factors for survival and pathogenesis, such as capsule, siderophores, lipopolysaccharide, fimbriae, outer membrane proteins, and type 6 secretion system, of which the former two are dominant. This review summarizes these hvKP-associated virulence factors in order to understand its molecular pathogenesis and shed light on new strategies to improve the prevention, diagnosis, and treatment of hvKP-causing infection.
Microbiome Modulation—Toward a Better Understanding of Plant Microbiome Response to Microbial Inoculants
Authors: Berg Gabriele , Kusstatscher Peter , Abdelfattah Ahmed , Cernava Tomislav , Smalla Kornelia
Published: April 2021

Plant-associated microorganisms are involved in important functions related to growth, performance and health of their hosts. Understanding their modes of action is important for the design of promising microbial inoculants for sustainable agriculture. Plant-associated microorganisms are able to interact with their hosts and often exert specific functions toward potential pathogens; the underlying in vitro interactions are well studied. In contrast, in situ effects of inoculants, and especially their impact on the plant indigenous microbiome was mostly neglected so far. Recently, microbiome research has revolutionized our understanding of plants as coevolved holobionts but also of indigenous microbiome-inoculant interactions. Here we disentangle the effects of microbial inoculants on the indigenous plant microbiome and point out the following types of plant microbiome modulations: (i) transient microbiome shifts, (ii) stabilization or increase of microbial diversity, (iii) stabilization or increase of plant microbiome evenness, (iv) restoration of a dysbiosis/compensation or reduction of a pathogen-induced shift, (v) targeted shifts toward plant beneficial members of the indigenous microbiota, and (vi) suppression of potential pathogens. Therefore, we suggest microbiome modulations as novel and efficient mode of action for microbial inoculants that can also be mediated via the plant.
Impact of COVID-19 Pandemic on Patients With Neurodegenerative Diseases
Authors: Hu Chao , Chen Cao , Dong Xiao-Ping
Published: April 2021

COVID-19 pandemic has already produced great impacts on global health security and social-economy. Elderly, particularly those with underlying diseases, are suffering from higher fatality rate. Neurodegenerative diseases are a group of incurable neurological disorders of loss of neuron and/or myelin sheath, which affect hundreds of millions of elderly populations and usually need long-term care. Older population is one of the most vulnerable to COVID-19 pandemic. In this report, we reviewed the current status of COVID-19 on the patients with several neurodegenerative diseases, particularly Alzheimer’s disease, Parkinson’s disease, prion disease, and amyotrophic lateral sclerosis. Meanwhile, the potential mechanisms of SARS-CoV-2 infection in the pathogenesis of neurodegenerative diseases were also summarized.
An Asymmetrical Hypothesis for the NREM-REM Sleep Alternation—What Is the NREM-REM Cycle?
Authors: Le Bon Olivier
Published: April 2021

Since the discovery of rapid eye movement (REM) sleep (Aserinsky and Kleitman, 1953), sleep has been described as a succession of cycles of non-REM (NREM) and REM sleep episodes. The hypothesis of short-term REM sleep homeostasis, which is currently the basis of most credible theories on sleep regulation, is built upon a positive correlation between the duration of a REM sleep episode and the duration of the interval until the next REM sleep episode (inter-REM interval): the duration of REM sleep would therefore predict the duration of this interval. However, the high variability of inter-REM intervals, especially in polyphasic sleep, argues against a simple oscillator model. A new “asymmetrical” hypothesis is presented here, where REM sleep episodes only determine the duration of a proportional post-REM refractory period (PRRP), during which REM sleep is forbidden and the only remaining options are isolated NREM episodes or waking. After the PRRP, all three options are available again (NREM, REM, and Wake). I will explain why I think this hypothesis also calls into question the notion of NREM-REM sleep cycles.
Current Methods to Investigate Nociception and Pain in Zebrafish
Authors: Ohnesorge Nils , Heinl Céline , Lewejohann Lars
Published: April 2021

Pain is an unpleasant, negative emotion and its debilitating effects are complex to manage. Mammalian models have long dominated research on nociception and pain, but there is increasing evidence for comparable processes in fish. The need to improve existing pain models for drug research and the obligation for 3R refinement of fish procedures facilitated the development of numerous new assays of nociception and pain in fish. The zebrafish is already a well-established animal model in many other research areas like toxicity testing, as model for diseases or regeneration and has great potential in pain research, too. Methods of electrophysiology, molecular biology, analysis of reflexive or non-reflexive behavior and fluorescent imaging are routinely applied but it is the combination of these tools what makes the zebrafish model so powerful. Simultaneously, observing complex behavior in free-swimming larvae, as well as their neuronal activity at the cellular level, opens new avenues for pain research. This review aims to supply a toolbox for researchers by summarizing current methods to study nociception and pain in zebrafish. We identify treatments with the best algogenic potential, be it chemical, thermal or electric stimuli and discuss options of analgesia to counter effects of nociception and pain by opioids, non-steroidal anti-inflammatory drugs (NSAIDs) or local anesthetics. In addition, we critically evaluate these practices, identify gaps of knowledge and outline potential future developments.
In situ Parallel Training of Analog Neural Network Using Electrochemical Random-Access Memory
Authors: Li Yiyang , Xiao T. Patrick , Bennett Christopher H. , Isele Erik , Melianas Armantas , Tao Hanbo , Marinella Matthew J. , Salleo Alberto , Fuller Elliot J. , Talin A. Alec
Published: April 2021

In-memory computing based on non-volatile resistive memory can significantly improve the energy efficiency of artificial neural networks. However, accurate in situ training has been challenging due to the nonlinear and stochastic switching of the resistive memory elements. One promising analog memory is the electrochemical random-access memory (ECRAM), also known as the redox transistor. Its low write currents and linear switching properties across hundreds of analog states enable accurate and massively parallel updates of a full crossbar array, which yield rapid and energy-efficient training. While simulations predict that ECRAM based neural networks achieve high training accuracy at significantly higher energy efficiency than digital implementations, these predictions have not been experimentally achieved. In this work, we train a 3 × 3 array of ECRAM devices that learns to discriminate several elementary logic gates (AND, OR, NAND). We record the evolution of the network’s synaptic weights during parallel in situ (on-line) training, with outer product updates. Due to linear and reproducible device switching characteristics, our crossbar simulations not only accurately simulate the epochs to convergence, but also quantitatively capture the evolution of weights in individual devices. The implementation of the first in situ parallel training together with strong agreement with simulation results provides a significant advance toward developing ECRAM into larger crossbar arrays for artificial neural network accelerators, which could enable orders of magnitude improvements in energy efficiency of deep neural networks.
Levofloxacin Versus Ciprofloxacin in the Treatment of Urinary Tract Infections: Evidence-Based Analysis
Authors: Cao Dehong , Shen Yinzhi , Huang Yin , Chen Bo , Chen Zeyu , Ai Jianzhong , Liu Liangren , Yang Lu , Wei Qiang
Published: April 2021

Urinary tract infections (UTIs) are one of the most common bacterial infections acquired both in community and hospital. Fluoroquinolones, represented by levofloxacin and ciprofloxacin, are widely used for treatment of UTIs. However, it remains controversial for the comparison between the 2 drugs, which propelled us to conduct the first evidence-based research on this topic. To establish their relative efficacy and safety, we searched Pubmed, embase, and Web of Science for randomized controlled trials (RCTs) for UTIs. A total of 5 RCTs were finally included, involving 2,352 patients and a systematic review and meta-analysis were performed to compare the end-of-therapy and posttherapy clinical success rate, microbial eradication rate and adverse event rate. Jadad score and Review Manager 5.3.0 version were applied respectively to evaluate the study quality and heterogeneity. There was no significant difference between levofloxacin and ciprofloxacin group in end-of-therapy or posttherapy clinical success rate and microbial eradication rate (p > 0.05). As for adverse event rate, the 2 drugs were comparable and both safe for clinical use. Based on one included trial and pharmacological research, we raised hypothesis that levofloxacin was superior to ciprofloxacin for treatment of E. coli-induced chronic bacterial prostatitis (CBP) and it required a further study to prove it.
Estimating the Growth Indices and Nitrogen Status Based on Color Digital Image Analysis During Early Growth Period of Winter Wheat
Authors: Zhao Ben , Zhang Yonghui , Duan Aiwang , Liu Zhandong , Xiao Junfu , Liu Zugui , Qin Anzhen , Ning Dongfeng , Li Sen , Ata-Ul-Karim Syed Tahir
Published: April 2021

The non-destructive estimation of plant nitrogen (N) status is imperative for timely and in-season crop N management. The objectives of this study were to use canopy cover (CC) to establish the empirical relations between plant growth indices [shoot dry matter (SDM), leaf area index (LAI), shoot N accumulation (SNA), shoot nitrogen concentration (SNC)], and CC as well as to test the feasibility of using CC to assess N nutrition index (NNI) from Feekes 3 to Feekes 6 stages of winter wheat. Four multi-locational (2 sites), multi-cultivars (four cultivars), and multi-N rates (0–300 kg N ha–1) field experiments were carried out during 2016 to 2018 seasons. The digital images of the canopy were captured by a digital camera from Feekes 3 to Feekes 6 stages of winter wheat, while SDM, LAI, SNA, and SNC were measured by destructive plant sampling. CC was calculated from digital images developed by self-programmed software. CC showed significant correlations with growth indices (SDM, LAI, and SNA) across the different cultivars and N treatments, except for SNC. However, the stability of these empirical models was affected by cultivar characteristics and N application rates. Plant N status of winter wheat was assessed using CC through two methods (direct and indirect methods). The direct and indirect methods failed to develop a unified linear regression to estimate NNI owing to the high dispersion of winter wheat SNC during its early growth stages. The relationships of CC with SDM, SNC and NNI developed at individual growth stages of winter wheat using both methods were highly significant. The relationships developed at individual growth stages did not need to consider the effect of N dilution process, yet their stability is influenced by cultivar characteristics. This study revealed that CC has larger limitation to be used as a proxy to manage the crop growth and N nutrition during the early growth period of winter wheat despite it is an easily measured index.
Psychological Lockdown Experiences: Downtime or an Unexpected Time for Being?
Authors: Procentese Fortuna , Esposito Ciro , Gonzalez Leone Florencia , Agueli Barbara , Arcidiacono Caterina , Freda Maria Francesca , Di Napoli Immacolata
Published: April 2021

The spread of COVID-19 in Italy resulted in the implementation of a lockdown that obligated the first time the general populace to remain at home for approximately two months. This lockdown interrupted citizens’ professional and educational activities, in addition to closing shops, offices and educational institutions. The resulting changes in people’s daily routines and activities induced unexpected changes in their thoughts, feelings and attitudes, in addition to altering their life perceptions. Consequently, the present study explores how young adults perceived their lives under lockdown during the final week of March 2020, when the reported number of daily coronavirus infections reached its peak in Italy. The research was carried out among 293 university students (234 women and 59 men) with an average age of 20.85 years old (SD = 3.23). The researchers asked participants to describe the emotions, thoughts and experiences that characterized their time under lockdown. The study analyzed specific narratives related to time and space using grounded theory methodology, which was applied using Atlas 8 software, leading to the creation of 68 codes. The study organized these codes into three specific categories: confined in the present, confined in the past, and striving toward one’s goals. Finally, the researchers also created a core-category labeled “continuity of being.” The results showed that the closure of open spaces caused a division in participants’ perceptions of time continuity, with many viewing themselves as feeling fragmented and as living the present in a static and fixed way. Additionally, participants also saw the present as being discontinuous from the past, while, simultaneously, projecting toward the future and the changes it might bring. Finally, this study examined further implications surrounding individual projecting among young people in greater depth.
“I Am Like a Lost Child”: L2 Writers' Linguistic Metaphors as a Window Into Their Writer Identity
Authors: Yang Shizhou , Peng Yinyin
Published: April 2021

The past two decades have witnessed a burgeoning literature on L2 writers' identities, especially their discoursal identities. In contrast, little attention is paid to the writers' felt sense of self when they write in an L2, which is an integral dimension of their autobiographical self. In this article, we provide empirical evidence of the nature of this aspect of L2 writer identity. To illustrate, we analyzed linguistic metaphors elicited from three groups of L2 writers (N = 83), majoring respectively in Thai, Japanese, and English in a Chinese university. Descriptive analysis shows that, due to challenges in content, language, organization, and cultural differences, a majority of L2 writers, especial Thai and Japanese L2 writers, experience a diminishing sense of self when they write in L2. In contrast, some L2 writers, especially English L2 writers, find writing in an L2 liberating, revealing the impact of their individual learning trajectories and pedagogical practices on L2 writers' felt sense of self. Findings suggest that L2 writers' identity work is both complex and dynamic. L2 writing teachers can utilize the metaphor questionnaire as a tool to facilitate their learner needs analysis and to raise L2 writers' metacognition.
Targeting Personal Recovery of People With Complex Mental Health Needs: The Development of a Psychosocial Intervention Through User-Centered Design
Authors: van der Meer Lisette , Jonker Tessa , Wadman Heleen , Wunderink Charlotte , van Weeghel Jaap , Pijnenborg Gerdina Hendrika Maria , van Setten Ellie R. H.
Published: April 2021

Long-term admissions in psychiatric facilities often result in a gradual erosion of the identity of people diagnosed with severe mental illnesses (SMIs) into merely “patient.” Moreover, experiences of loss often reduced people's sense of purpose. Although regaining a multidimensional identity and a sense of purpose are essential for personal recovery, few interventions specifically address this, while at the same time take people's often considerable cognitive and communicative disabilities into consideration. This study describes the development process of a new intervention through user-centered design (UCD). UCD is an iterative process in which a product (in this case, an intervention) is developed in close cooperation with future users, such that the final product matches their needs. The design process included three phases: an analysis, design, and evaluation phase. In the analysis phase, the “problem” was defined, users' needs were identified, and design criteria were established. In the design phase, the collected information served as input to create a testable prototype using a process of design and redesign, in close collaboration with service users and other stakeholders. This resulted in an intervention entitled “This is Me” (TiM) in which service users, together with a self-chosen teammate, actively engage in new experiences on which they are prompted to reflect. Finally, in the evaluation phase, TiM was implemented and evaluated in a real-life setting. In a small feasibility pilot, we found indications that some people indeed demonstrated increased reflection on their identity during the intervention. Furthermore, TiM seemed to benefit the relationship between the service users and the mental health professionals with whom they underwent the experiences. The pilot also revealed some aspects of the (implementation of) TiM that can be improved. Overall, we conclude that UCD is a useful method for the development of a new psychosocial intervention. The method additionally increased our knowledge about necessary factors in targeting personal recovery for people with complex mental health needs. Moreover, we conclude that TiM is a promising tool for supporting people with SMI in redeveloping a multidimensional identity and a renewed sense of purpose.
Can FT-Mid-Infrared Spectroscopy of Milk Samples Discriminate Different Dietary Regimens of Sheep Grazing With Restricted Access Time?
Authors: Molle Giovanni , Cabiddu Andrea , Decandia Mauro , Sitzia Maria , Ibba Ignazio , Giovanetti Valeria , Scanu Giuseppe , Addis Margherita , Caredda Marco
Published: April 2021

Milk obtained from sheep grazing natural pastures and some forage crops may be worth a plus value as compared to milk obtained from stall-fed sheep, due to their apparently higher content of beneficial fatty acids (FAs). Fourier transformed mid-infrared (FT-MIR) analysis of FA can help distinguish milk from different areas and diverse feeding systems. The objective was to discriminate milk from sheep and milk from dairy sheep rotationally grazing Italian ryegrass or berseem clover for 2, 4, or 6 h/day. To test this hypothesis, a data-mining study was undertaken using a database of 1,230 individual milk spectra. Data were elaborated by principal component analysis (PCA) and analyzed by linear discriminant analysis (LDA) with or without the use of genetic algorithm (GA) as a variable selection tool with the primary aim to discriminate grazed forages (grass vs. legume), access time (2, 4, or 6 h/day), grazing day (first vs. last grazing day during the 7-day grazing period), and the milking time (morning vs. afternoon milking). The best-fitting discriminant models of FT-MIR spectra were able to correctly predict 100% of the samples differing for the pasture forage, 91.9% of the samples differing for grazing day, and 97.1% of the samples regarding their milking time. The access time (AT) to pasture was correctly predicted by the model in 60.3% of the samples, and the classification ability was improved to 77.0% when considering only the 2 and 6 h/day classes.