bluuebunny/crossref_metadata_2025 huggingface dataset:
Kidney Cancer Models for Pre-Clinical Drug Discovery: Challenges and Opportunities
Authors: Pohl Laura , Friedhoff Jana , Jurcic Christina , Teroerde Miriam , Schindler Isabella , Strepi Konstantina , Schneider Felix , Kaczorowski Adam , Hohenfellner Markus , Duensing Anette , Duensing Stefan
Published: May 2022

Renal cell carcinoma (RCC) is among the most lethal urological malignancies once metastatic. The introduction of immune checkpoint inhibitors has revolutionized the therapeutic landscape of metastatic RCC, nevertheless, a significant proportion of patients will experience disease progression. Novel treatment options are therefore still needed and in vitro and in vivo model systems are crucial to ultimately improve disease control. At the same time, RCC is characterized by a number of molecular and functional peculiarities that have the potential to limit the utility of pre-clinical model systems. This includes not only the well-known genomic intratumoral heterogeneity (ITH) of RCC but also a remarkable functional ITH that can be shaped by influences of the tumor microenvironment. Importantly, RCC is among the tumor entities, in which a high number of intratumoral cytotoxic T cells is associated with a poor prognosis. In fact, many of these T cells are exhausted, which represents a major challenge for modeling tumor-immune cell interactions. Lastly, pre-clinical drug development commonly relies on using phenotypic screening of 2D or 3D RCC cell culture models, however, the problem of “reverse engineering” can prevent the identification of the precise mode of action of drug candidates thus impeding their translation to the clinic. In conclusion, a holistic approach to model the complex “ecosystem RCC” will likely require not only a combination of model systems but also an integration of concepts and methods using artificial intelligence to further improve pre-clinical drug discovery.
Long-Term Survival of a Lynch Syndrome Patient With Eight Primary Tumors: A Case Report
Authors: Jiang Jing , Huang Ting , Lin Xianlei , Zhang Yu , Yang Xuefei , Huang Ling , Ye Zhifeng , Ren Xingchang , Teng Lisong , Li Jun , Kong Mei , Lian Liyan , Lu Jinhua , Zhong Yazhen , Lin Zechen , Xu Ming , Chen Yin , Lin Shengyou
Published: May 2022

With the modern technological developments in the diagnosis and treatment of cancer, the survival rate of cancer patients has increased. On the other hand, the incidence of multiple primary tumors is increasing annually. Lynch syndrome (LS), an autosomal dominant disorder with germline mutations in DNA mismatch repair genes, increases the risk of cancer in patients carrying those mutations. In this report, we present an extremely rare case of an 81-year-old male patient with eight primary malignancies and LS. The patient is still alive having survived for more than 41 years since the initial discovery of the first tumor. The eighth and most recently diagnosed primary cancer was a malignant peripheral nerve sheath tumor. Although there have been numerous reports of malignancies in LS, malignant peripheral nerve sheath tumors have not been reported previously with LS. Here, we report, to the best of our knowledge, the first case of a malignant peripheral nerve sheath tumor with LS.
Maternal Smoking, Alcohol and Recreational Drug Use and the Risk of SIDS Among a US Urban Black Population
Authors: Hauck Fern R. , Blackstone Sarah R.
Published: May 2022

Background

Rates of sudden infant death syndrome (SIDS) are twice as high among Black infants compared to white infants in the US. While the contribution of sleep environment factors to this disparity is known, little is known about the risk of SIDS among Black infants in relation to maternal prenatal smoking, alcohol and drug use as well as infant smoke exposure.

Objective

To assess the contribution of maternal substance use during pregnancy and the potential interactions with infant bedsharing in a high-risk, urban Black population.

Methods

The Chicago Infant Mortality Study (CIMS) collected data on 195 Black infants who died of SIDS and 195 controls matched on race, age and birthweight. Risk of SIDS was calculated for maternal smoking, alcohol and drug use, adjusting for potential confounding variables and other risk factors for SIDS. Interactions between these substance use variables and bedsharing were also calculated.

Results

Infants were more likely to die from SIDS if the mother smoked during pregnancy (aOR 3.90, 95% CI 1.37–3.30) and post-pregnancy (aOR 2.49, 95% CI 1.49–4.19). There was a dose response seen between amount smoked during pregnancy and risk of SIDS. Use of alcohol (aOR 2.89, 95% CI 1.29–6.99), cocaine (aOR 4.78, 95% CI 2.45–9.82) and marijuana (aOR 2.76, 95% CI 1.28–5.93) were associated with increased risk of SIDS. In the final, multivariable model controlling for sociodemographic factors and covariates, maternal smoking (aOR 3.03, 95% CI 1.03–8.88) and cocaine use (aOR 4.65, 95% CI 1.02–21.3) during pregnancy remained significant. There were significant, positive interactions between bedsharing and maternal smoking during pregnancy and post-pregnancy, alcohol use and cocaine use.

Conclusion

Maternal use of tobacco, alcohol and cocaine during pregnancy is associated with significantly increased risk of SIDS in a Black, urban population. Reducing substance use and eliminating disparities in SIDS, sudden unexpected infant death (SUID) (also known as sudden unexpected death in infancy or SUDI) and infant mortality need to involve more than individual level education, but instead will require a comprehensive examination of the role of social determinants of health as well as a multi-pronged approach to address both maternal and infant health and wellbeing.
Ignorance Isn't Bliss: We Must Close the Machine Learning Knowledge Gap in Pediatric Critical Care
Authors: Ehrmann Daniel , Harish Vinyas , Morgado Felipe , Rosella Laura , Johnson Alistair , Mema Briseida , Mazwi Mjaye
Published: May 2022

Pediatric intensivists are bombarded with more patient data than ever before. Integration and interpretation of data from patient monitors and the electronic health record (EHR) can be cognitively expensive in a manner that results in delayed or suboptimal medical decision making and patient harm. Machine learning (ML) can be used to facilitate insights from healthcare data and has been successfully applied to pediatric critical care data with that intent. However, many pediatric critical care medicine (PCCM) trainees and clinicians lack an understanding of foundational ML principles. This presents a major problem for the field. We outline the reasons why in this perspective and provide a roadmap for competency-based ML education for PCCM trainees and other stakeholders.
Giant Pediatric Supratentorial Tumor: Clinical Feature and Surgical Strategy
Authors: Zhang Zhong-Ding , Fang Huang-Yi , Pang Chen , Yang Yue , Li Shi-Ze , Zhou Ling-Li , Bai Guang-Hui , Sheng Han-Song
Published: May 2022

Purpose

To analyze the clinical character of giant pediatric supratentorial tumor (GPST) and explore prognostic factors.

Materials and Methods

We analyzed the clinical data comprising of 35 cases of GPST from a single center between January 2015 and December 2020. The tumor volume was measured by 3D slicer software based on preoperative magnetic resonance imaging (MRI). Glasgow Outcome Scale (GOS) was used to evaluate the short-term prognosis.

Result

The tumor volume varied from 27.3 to 632.8 ml (mean volume 129.8 ml/ median volume 82.8 ml). Postoperative histopathological types include ependymoma, pilocytic astrocytoma, choroid plexus papilloma (CPP), craniopharyngioma, primitive neuroectoderm tumor (PNET), choroid plexus carcinoma (CPC), immature teratoma, atypical teratoid rhabdoid tumor (AT/RT), anaplastic astrocytoma, and gangliocytoma. Tumors in children younger than 3 years and tumors located at the hemispheres appeared to be larger than their respective counterparts, though no statistical significance was found. A patient with giant immature teratoma died during the operation because of excessive bleeding. Postoperative complications include cerebrospinal fluid subgaleal collection/effusion, infection, neurological deficits, and seizures. The mean GOS score of patients with GPST in 6 months is 3.43 ± 1.12, and 83% of patients (29/35) showed improvement. Favorable GPST characteristics to indicated better GOS included small tumor (≤100 ml) (p = 0.029), low-grade (WHO I-II) (p = 0.001), and gross total resection (GTR) (p = 0.015). WHO grade was highly correlated with GOS score (correlation coefficient = −0.625, p < 0.001). GTR and tumor volume were also correlated (correlation coefficient = −0.428, p = 0.010).

Conclusion

The prognosis of GPST is highly correlated with the histopathological type. Smaller tumors are more likely to achieve GTR and might lead to a higher GOS score. Early diagnosis and GTR of the tumor are important for GPST management.
Nrf2 Activation With CDDO-Methyl Promotes Beneficial and Deleterious Clinical Effects in Transgenic Mice With Sickle Cell Anemia
Authors: Ihunnah Chibueze A. , Ghosh Samit , Hahn Scott , Straub Adam C. , Ofori-Acquah Solomon F.
Published: May 2022

Activation of Nrf2, a major transcription factor that drives the antioxidant defense system, is an emerging therapeutic strategy in Sickle Cell Disease (SCD). In this study, transgenic Sickle Cell Anemia mice (SS mice) treated with CDDO-Methyl (CDDO-Me), a potent Nrf2 activator, showed reduced progression of hemolytic anemia with aging, but surprisingly also showed reduced endothelial function. Pulmonary vessels isolated from SS mice treated for 4 months with CDDO-Me displayed a diminished response to nitric oxide (NO)-induced vasodilation compared to littermates given vehicle. It is unclear what molecular mechanism underly the vascular impairment, however, our in vitro assays revealed that CDDO-Me induced the expression of the endothelin receptor (ETA and ETB) in vascular smooth muscle cells. Endothelin signaling is associated with increased vascular tone and vasoconstriction. This study underscores the importance of pre-clinical benefit-risk investigations of Nrf2 activating compounds which may be used to treat patients with SCD.
Network Pharmacology Analysis of Huangqi Jianzhong Tang Targets in Gastric Cancer
Authors: Li Long , Lu Yizhuo , Liu Yanling , Wang Dan , Duan Linshan , Cheng Shuyu , Liu Guoyan
Published: May 2022

Graphical Abstract
Applying Dialysis Bags to Grow Microalgae and Measure Grazing Rates by Secondary Producers
Authors: Tian Yang , Yi Xiangqi , Gao Kunshan
Published: May 2022

Traditional methods using sealed bottles to determine the grazing rates by secondary producers neglect chemical changes induced by biological activities during the incubation, giving rise to instable levels of nutrients, pH, pCO2, pO2 and other chemicals along with changing microalgal cell concentrations and grazers’ metabolism. Here, we used dialysis bags, which allows exchanges of nutrients and gases, to grow microalgae and to determine grazing rates of secondary producers. The specific growth rate of diatom within the dialysis bags increased with increasing water velocities, indicating its suitability to grow microalgae under dynamic water conditions. Then, we compared the grazing rates by the heterotrophic dinoflagellate Noctiluca scintillans measured with the traditional method using polycarbonate (PC) bottles and the approach with the dialysis bags, and found that these two methods gave rise to comparable grazing rates. Nevertheless, the concentrations of inorganic nitrogen and phosphate in the closed PC bottles were about 89–94% lower than those in the dialysis bags due to the microalga’s assimilation. Subsequently, we applied it to determine the grazing rates by a copepod and an oyster (in the presence of other grazers). Consistent results were obtained using the dialysis bags to determine grazing rates by copepods. During the mesocosm (3000 L) experiment in the presence of primary and secondary producers, the grazing rates by the oyster Crassostrea angulata were determined based on the difference of phytoplankton biomass within and outside of the dialysis bags that held all organisms in the mesocosm except the oyster. Since the dialysis bags are permeable to gases, the grazing rates by the oyster under 410 (AC) and 1,000 (HC) μatm CO2 were successfully measured, with a promising result that HC significantly increased the oyster’s grazing. We concluded that using dialysis bags to grow microalgae and to determine grazing rates is a reliable approach, especially under different levels of CO2 and O2.
Urine-Derived Stem Cells Versus Their Lysate in Ameliorating Erectile Dysfunction in a Rat Model of Type 2 Diabetes
Authors: Galhom Rania A. , Korayem Horeya Erfan , Ibrahim Mahrous A. , Abd-Eltawab Tammam Ahmed , Khalifa Mohamed Mansour , Rashwan Eman K. , Al Badawi Manal H.
Published: May 2022

Background: Diabetic erectile dysfunction (DED) is a significant consequence of diabetes mellitus, and it is a multifactorial phenomenon that has no definitive treatment until now. Many therapeutic options provide symptomatic improvement rather than addressing the underlying etiology or restoring normal function. Stem cell (SC) therapy represents a potential hope in DED management. It is well established that the regenerative effect of stem cells can be attained by their paracrine action and their ability to differentiate into many cell lineages, including endothelial and smooth muscle cells. Hence, we tried to compare the effects of transplantation of urine-derived stem cells (USCs) or their lysate (USC-L) into the corpora cavernosa (CCs) of rats with DED.

Materials and Methods: A total of 55 adult male Wistar rats were included in this study. USCs were obtained from ten healthy rats. Another ten rats did not subject to any intervention and served as a control (group I). Type 2 DM and DED were induced in the remaining 35 rats, but DED was tested and proved in only 24 rats, which were randomly divided into three groups (n = 8 in each). The DED group (group II) and either USCs (2 × 106 cells) or their lysate (200 μl) were transplanted into the CCs of each rat in the other two groups (groups III and IV), respectively.

Results: Although the DED rats exhibited deterioration in all copulatory functions as compared to the control group, our histopathological, immunohistochemical, and morphometric results revealed that both USCs and USC-L have significantly restored the cavernous spaces, the ultrastructures of the endothelium that line the cavernous spaces, collagen/smooth muscle ratio, and the mean area percentage of α-SMA in the CCs as compared to DED rats. A respectable number of USCs was detected in the CCs of group III at the 4th week after transplantation, but this number significantly declined by the 8th week.

Conclusion: Both USCs and USC-L can repair the structure and ultrastructure of CCs and improve the copulatory functions in the DED rat model. However, USC-L could be better used in DED to guard against the strange behavior of USCs after transplantation and their decreased survivability with time.
Administration of Drugs/Gene Products to the Respiratory System: A Historical Perspective of the Use of Inert Liquids
Authors: Alapati Deepthi , Shaffer Thomas H.
Published: May 2022

The present review is a historical perspective of methodology and applications using inert liquids for respiratory support and as a vehicle to deliver biological agents to the respiratory system. As such, the background of using oxygenated inert liquids (considered a drug when used in the lungs) opposed to an oxygen-nitrogen gas mixture for respiratory support is presented. The properties of these inert liquids and the mechanisms of gas exchange and lung function alterations using this technology are described. In addition, published preclinical and clinical trial results are discussed with respect to treatment modalities for respiratory diseases. Finally, this forward-looking review provides a comprehensive overview of potential methods for administration of drugs/gene products to the respiratory system and potential biomedical applications.
Nature vs. Nurture: Disentangling the Influence of Inheritance, Incubation Temperature, and Post-Natal Care on Offspring Heart Rate and Metabolism in Zebra Finches
Authors: Hope Sydney F. , Schmitt Louise , Lourdais Olivier , Angelier Frédéric
Published: May 2022

A historic debate in biology is the question of nature vs. nurture. Although it is now known that most traits are a product of both heredity (“nature”) and the environment (“nurture”), these two driving forces of trait development are rarely examined together. In birds, one important aspect of the early developmental environment is egg incubation temperature. Small changes (<1°C) in incubation temperature can have large effects on a wide-array of offspring traits. One important trait is metabolism, because it is related to life-history traits and strategies, organismal performance, and energetic and behavioral strategies. Although it has been shown that embryonic and post-hatch metabolism are related to egg incubation temperature, little is known about how this may vary as a function of genetic differences or post-hatching environmental conditions. Here, we investigated this question in zebra finches (Taeniopygia guttata). We experimentally incubated eggs at two different temperatures: 37.5°C (control), which is optimal for this species and 36.3°C (low), which is suboptimal. We first measured embryonic heart rate as a proxy of embryonic metabolic rate. Then, at hatch, we cross-fostered nestlings to differentiate genetic and pre-hatching factors from post-hatching environmental conditions. When offspring were 30 days-old, we measured their resting metabolic rate (RMR; within the thermoneutral zone) and thermoregulatory metabolic rate (TMR; 12°C; birds must actively thermoregulate). We also measured RMR and TMR of all genetic and foster parents. We found that embryonic heart rate was greater in eggs incubated at the control temperature than those at the low temperature. Further, embryonic heart rate was positively related to genetic father RMR, suggesting that it is both heritable and affected by the pre-natal environment. In addition, we found that post-hatch metabolic rates were positively related to genetic parent metabolic rate, and interactively related to incubation temperature and foster mother metabolic rate. Altogether, this suggests that metabolism and the energetic cost of thermoregulation can be influenced by genetics, the pre-natal environment, and the post-natal environment. Our study sheds light on how environmental changes and parental care may affect avian physiology, as well as which traits may be susceptible to natural selection.
Regenerative Calcium Currents in Renal Primary Cilia
Authors: Kleene Steven J.
Published: May 2022

Polycystic kidney disease (PKD) is a leading cause of end-stage renal disease. PKD arises from mutations in proteins, one a Ca2+-conducting channel, expressed in the primary cilia of renal epithelial cells. A common hypothesis is that Ca2+ entering through ciliary ion channels may reduce cystogenesis. The cilia have at least two Ca2+-conducting channels: polycystin-2 (PC2) and TRPV4 (transient receptor potential (TRP) cation channel, subfamily V, member 4), but how substantially they can increase intraciliary Ca2+ is unknown. By recording channel activities in isolated cilia, conditions are identified under which the channels can increase free Ca2+ within the cilium by at least 500-fold through regenerative (positive-feedback) signaling. Ca2+ that has entered through a channel can activate the channel internally, which increases the Ca2+ influx, and so on. Regenerative signaling is favored when the concentration of the Ca2+ buffer is reduced or when a slower buffer is used. Under such conditions, the Ca2+ that enters the cilium through a single PC2 channel is sufficient to almost fully activate that same channel. Regenerative signaling is not detectable with reduced external Ca2+. Reduced buffering also allows regenerative signaling through TRPV4 channels, but not through TRPM4 (TRP subfamily M, member 4) channels, which are activated by Ca2+ but do not conduct it. On a larger scale, Ca2+ that enters through TRPV4 channels can cause secondary activation of PC2 channels. I discuss the likelihood of regenerative ciliary Ca2+ signaling in vivo, a possible mechanism for its activation, and how it might relate to cystogenesis.
A Review of Healthy and Fibrotic Myocardium Microstructure Modeling and Corresponding Intracardiac Electrograms
Authors: Sánchez Jorge , Loewe Axel
Published: May 2022

Computational simulations of cardiac electrophysiology provide detailed information on the depolarization phenomena at different spatial and temporal scales. With the development of new hardware and software, in silico experiments have gained more importance in cardiac electrophysiology research. For plane waves in healthy tissue, in vivo and in silico electrograms at the surface of the tissue demonstrate symmetric morphology and high peak-to-peak amplitude. Simulations provided insight into the factors that alter the morphology and amplitude of the electrograms. The situation is more complex in remodeled tissue with fibrotic infiltrations. Clinically, different changes including fractionation of the signal, extended duration and reduced amplitude have been described. In silico, numerous approaches have been proposed to represent the pathological changes on different spatial and functional scales. Different modeling approaches can reproduce distinct subsets of the clinically observed electrogram phenomena. This review provides an overview of how different modeling approaches to incorporate fibrotic and structural remodeling affect the electrogram and highlights open challenges to be addressed in future research.
Homing in on Endogenous Badnaviral Elements: Development of Multiplex PCR-DGGE for Detection and Rapid Identification of Badnavirus Sequences in Yam Germplasm
Authors: Silva Gonçalo , Bömer Moritz , Turaki Aliyu A. , Nkere Chukwuemeka K. , Kumar P. Lava , Seal Susan E.
Published: May 2022

Viruses of the genus Badnavirus (family Caulimoviridae) are double-stranded DNA-reverse transcribing (dsDNA-RT) plant viruses and have emerged as serious pathogens of tropical and temperate crops globally. Endogenous badnaviral sequences are found integrated in the genomes of several economically important plant species. Infection due to activation of replication-competent integrated copies of the genera Badnavirus, Petuvirus and Cavemovirus has been described. Such endogenous badnaviral elements pose challenges to the development of nucleic acid-based diagnostic methods for episomal virus infections and decisions on health certification for international movement of germplasm and seed. One major food security crop affected is yam (Dioscorea spp.). A diverse range of Dioscorea bacilliform viruses (DBVs), and endogenous DBV (eDBV) sequences have been found to be widespread in yams cultivated in West Africa and other parts of the world. This study outlines the development of multiplex PCR-dependent denaturing gradient gel electrophoresis (PCR-DGGE) to assist in the detection and analysis of eDBVs, through the example of analysing yam germplasm from Nigeria and Ghana. Primers targeting the three most prevalent DBV monophyletic species groups in West Africa were designed to improve DGGE resolution of complex eDBV sequence fingerprints. Multiplex PCR-DGGE with the addition of a tailor-made DGGE sequence marker enables rapid comparison of endogenous badnaviral sequence diversity across germplasm, as illustrated in this study for eDBV diversity in yam.
Genome-Wide Investigation of the PtrCHLP Family Reveals That PtrCHLP3 Actively Mediates Poplar Growth and Development by Regulating Photosynthesis
Authors: He Fang , Shi Yu-Jie , Chen Qi , Li Jun-Lin , Niu Meng-Xue , Feng Cong-Hua , Lu Meng-Meng , Tian Fei-Fei , Zhang Fan , Lin Tian-Tian , Chen Liang-Hua , Liu Qin-lin , Wan Xue-Qin
Published: May 2022

Chlorophyll (Chl) plays a crucial role in plant photosynthesis. The geranylgeraniol reductase gene (CHLP) participates in the terminal hydrogenation of chlorophyll biosynthesis. Although there are many studies related to the genome-wide analysis of Populus trichocarpa, little research has been conducted on CHLP family genes, especially those concerning growth and photosynthesis. In this study, three CHLP genes were identified in Populus. The evolutionary tree indicated that the CHLP family genes were divided into six groups. Moreover, one pair of genes was derived from segmental duplications in Populus. Many elements related to growth were detected by cis-acting element analysis of the promoters of diverse PtrCHLPs. Furthermore, PtrCHLPs exhibit different tissue expression patterns. In addition, PtrCHLP3 is preferentially expressed in the leaves and plays an important role in regulating chlorophyll biosynthesis. Silencing of PtrCHLP3 in poplar resulted in a decrease in chlorophyll synthesis in plants, thus blocking electron transport during photosynthesis. Furthermore, inhibition of PtrCHLP3 expression in poplar can inhibit plant growth through the downregulation of photosynthesis. Ultimately, PtrCHLP3 formed a co-expression network with photosynthesis and chlorophyll biosynthesis-related genes, which synergistically affected the growth and photosynthesis of poplars. Thus, this study provides genetic resources for the improved breeding of fast-growing tree traits.
The Small Secreted Protein FoSsp1 Elicits Plant Defenses and Negatively Regulates Pathogenesis in Fusarium oxysporum f. sp. cubense (Foc4)
Authors: Wang Yuhua , Zhang Xinchun , Wang Tian , Zhou Siyu , Liang Xiaofei , Xie Changping , Kang Zhensheng , Chen Daipeng , Zheng Li
Published: May 2022

Fusarium wilt of banana (Musa spp.), a typical vascular wilt disease caused by the soil-borne fungus, Fusarium oxysporum f. sp. cubense race 4 (Foc4), seriously threatens banana production worldwide. Pathogens, including vascular wilt fungi, secrete small cysteine-rich proteins during colonization. Some of these proteins are required for pathogenicity. In this study, 106 small secretory proteins that contain a classic N-terminal signal peptide were identified using bioinformatic methods in Foc4. Among them, 11 proteins were selected to show transient expressions in tobacco. Interestingly, transient expression of FoSsp1 in tobacco, an uncharacterized protein (of 145 aa), induced necrotic cell death reactive oxygen burst, and callous deposition. Furthermore, the expression of FoSSP1 in Foc4 wild type (WT) was up-regulated during the stage of banana roots colonization. A split-marker approach was used to knock out FoSSP1 in the Foc4 WT strain. Compared with the WT, the deletion mutant Fossp1 was normal in growth rate but increased in conidiation and virulence. RT-qPCR analysis showed that the expression of four conidiation regulator genes in the Fossp1 deletion mutant was significantly decreased compared to the WT strain. In addition, the expression of four pathogenesis-related genes of bananas infected with Fossp1 deletion mutant was down-regulated in comparison with that of the WT. In summary, these results suggested that FoSSP1 is a putative elicitor that negatively regulates conidiation and pathogenicity in Foc4.
Nicotianabenthamiana, a Surrogate Host to Study Novel Virulence Mechanisms of Gram-Positive Bacteria, Clavibacter michiganensis, and C. capsici in Plants
Authors: Park In Woong , Hwang In Sun , Oh Eom-Ji , Kwon Choon-Tak , Oh Chang-Sik
Published: May 2022

Clavibacter michiganensis is a Gram-positive bacterium that causes bacterial canker and wilting in host plants like tomato. Two major virulence genes encoding a cellulase (celA) and a putative serine protease (pat-1) have been reported. Here we show that Nicotiana benthamiana, a commonly used model plant for studying molecular plant–pathogen interactions, is a surrogate host of C. michiganensis and C. capsici. When a low concentration of two Clavibacter species, C. michiganensis and C. capsici, were infiltrated into N. benthamiana leaves, they caused blister-like lesions closely associated with cell death and the generation of reactive oxygen species and proliferated significantly like a pathogenic bacterium. By contrast, they did not cause any disease symptoms in N. tabacum leaves. The celA and pat-1 mutants of C. michiganensis still caused blister-like lesions and cankers like the wild-type strain. When a high concentration of two Clavibacter species and two mutant strains were infiltrated into N. benthamiana leaves, all of them caused strong and rapid necrosis. However, only C. michiganensis strains, including the celA and pat-1 mutants, caused wilting symptoms when it was injected into stems. When two Clavibacter species and two mutants were infiltrated into N. tabacum leaves at the high concentration, they (except for the pat-1 mutant) caused a strong hypersensitive response. These results indicate that C. michiganensis causes blister-like lesions, canker, and wilting in N. benthamiana, and celA and pat-1 genes are not necessary for the development of these symptoms. Overall, N. benthamiana is a surrogate host of Clavibacter species, and their novel virulence factors are responsible for disease development in this plant.
Sap Flow Velocity in Fraxinus pennsylvanica in Response to Water Stress and Microclimatic Variables
Authors: Su Yu , Wang Xinyu , Sun Yiqiu , Wu Hailong
Published: May 2022

In arid and semiarid regions with water shortage, forestry development is limited by water availability. Understanding how tree sap flow responds to water stress and microclimatic variables is essential for the management of trees and the understanding of the eco-physiological properties of trees in arid areas. In the city of Tianjin in northern China, we measured the sap flow of Fraxinus pennsylvanica, a widely distributed urban greening tree species in semiarid regions of China. We measured the sap flow in four F. pennsylvanica trees over 6 months (April–September 2021), using a thermal diffusion probe method, and simultaneously monitored microclimatic variables and soil moisture. Results indicated that high nighttime sap flow velocity might be produced under the water stress condition. In addition, the nighttime sap flow velocity under the water stress condition was more susceptible to the combined effects of meteorological factors at night. The daytime sap flow velocity exerted a highly significant positive effect on the nighttime sap flow velocity during the whole research period, and the model fit was higher in the early growing season than that in the late growing season (early growing season: R2 = 0.51, P < 0.01; late growing season: R2 = 0.36, P < 0.01). Vapor pressure deficit had a positive effect on daytime sap flow. However, net vapor pressure deficit restrained daytime sap flow velocity when the intercorrelation between the microclimatic variables was removed. Our study highlights that drought areas perhaps have higher nighttime sap flow and that more emphasis should be placed on nighttime sap flow and the response of nighttime sap flow to microclimatic variables. In addition, the influence of other microclimatic variables on vapor pressure deficit needs to be considered when analyzing the relationship between daytime sap flow and vapor pressure deficit. An increase in net VPD can suppress the daytime sap flow.
Calcium Regulates Growth and Nutrient Absorption in Poplar Seedlings
Authors: Weng Xiaohang , Li Hui , Ren Chengshuai , Zhou Yongbin , Zhu Wenxu , Zhang Songzhu , Liu Liying
Published: May 2022

As a crucial element for plants, calcium (Ca) is involved in photosynthesis and nutrient absorption, and affects the growth of plants. Poplar is an important economic forest and shelter forest species in China. However, the optimum calcium concentration for its growth is still unclear. Herein, we investigated the growth, biomass, photosynthetic pigments, photosynthetic parameters and products, chlorophyll fluorescence parameters, water use efficiency (iWUE), and antioxidant enzyme activity of “Liao Hu NO.1” poplar (P. simonii × P. euphratica) seedlings at 0, 2.5, 5, 10, and 20 mmol·L−1 concentrations of Ca2+, and further studied the absorption, distribution, and utilization of nutrient elements (C, N, P, K, and Ca) in plants. We found that with increasing calcium gradient, plant height and diameter; root, stem, leaf, and total biomasses; net photosynthetic rate (Pn); stomatal conductance (Gs); intercellular carbon dioxide (Ci) level; transpiration rate (Tr); Fv/Fm ratio; Fv/F0 ratio; chlorophyll-a; chlorophyll-b; soluble sugar and starch content; superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) levels; and long-term water use efficiency (iWUE) of poplar seedlings first increased and then decreased. These parameters attained maximum values when the calcium concentration was 5 mmol·L−1, which was significantly different from the other treatments (P < 0.05). Moreover, a suitable Ca2+ level promoted the absorption of C, N, P, K, and Ca by various organs of poplar seedlings. The absorption of C, N, P, and K increased first and then decreased with the increased calcium concentration, but the optimum calcium concentrations for the absorption of different elements by different organs were different, and the calcium concentration in leaves, stems, and roots increased gradually. Furthermore, the increase in exogenous calcium content led to a decreasing trend in the C/N ratio in different organs of poplar seedlings. C/P and N/P ratios showed different results in different parts, and only the N/P ratio in leaves showed a significant positive correlation with Ca2+ concentration. In conclusion, the results of this study indicate that 5 mmol·L−1 concentration of Ca2+ is the optimal level, as it increased growth by enhancing photosynthesis, stress resistance, and nutrient absorption.
Heartfulness Meditation: A Yogic and Neuroscientific Perspective
Authors: van’t Westeinde Annelies , Patel Kamlesh D.
Published: May 2022

Today, as research into the contemplative sciences is being widely referenced, the research community would benefit from an understanding of the Heartfulness method of meditation. Heartfulness offers an in-depth experiential practice focused on the evolution of human consciousness using the ancient technique of Pranahuti (yogic Transmission) during Meditation, in combination with the more active mental practice of “Cleaning.” Both are enabled by initiation into the Heartfulness practices. These unique features distinguish Heartfulness from other paths that have been described in the scientific literature thus far. In this introductory paper, we present the Heartfulness practices, the philosophy upon which the practices are based, and we reflect on the putative mechanisms through which Heartfulness could exert its effects on the human body and mind in the light of scientific research that has been done in other meditation systems. We conclude with suggestions for future research on the Heartfulness way of meditation.
Adolescent Addiction to Short Video Applications in the Mobile Internet Era
Authors: Lu Lihong , Liu Mei , Ge Binchao , Bai Zijin , Liu Ziqi
Published: May 2022

The adolescent addiction to short video applications is becoming increasingly prominent, which has brought great challenges to the physical and mental health and daily life of the adolescents. This manuscript conducts an empirical study on the contributing factors of the adolescent addiction to short video applications based on the user generated content (UGC). In our study, 96 participants aged 15–25 were surveyed by questionnaire, and then cross-analysis of individual factors and SEM analysis of UGC content factors were carried out. Through the analysis of individual factors of the adolescent addiction from the perspective of gender, age, and family environment, this study reveals that male users are more addicted to the use of applications (APP), and such addiction varies with age, and prolonged family members’ use of short video APP can also exacerbate the adolescent addiction degree. Furthermore, through verification of the theoretical model, it indicates that UGC perception and the degree of boredom in daily life have a significant positive effect on the level of addiction to short video applications, and the degree of boredom in daily life plays a significant mediating role between them. Based on the research on the influences of UGC on the adolescent immersive experience, this study proposes a mechanism of the adolescent addiction to the use of short video applications in the mobile Internet age to provide a better service guarantee for the adolescents.
Transcutaneous Electrical Cranial-Auricular Acupoint Stimulation vs. Escitalopram for Patients With Mild-to-Moderate Depression (TECAS): Study Design for a Randomized Controlled, Non-inferiority Trial
Authors: Yang Sichang , Qin Zongshi , Yang Xinjing , Chan Mei Yan , Zhang Shuiyan , Rong Peijing , Hou Xiaobing , Jin Guixing , Xu Fengquan , Liu Yong , Zhang Zhang-Jin
Published: May 2022

Background

Previous studies in animals and humans indicated that transcutaneous vagus nerve stimulation (tVNS) and transcutaneous electrical acupoint stimulation (TEAS) on trigeminal nerve-innervated forehead acupoints can relief the symptoms of depression. However, due to the limited investigations on these two interventions, more research are needed to confirm their efficacy in depression. To improve the efficacy of the single treatment, we combined two treatments and created a novel non-invasive stimulation, transcutaneous electrical cranial-auricular acupoint stimulation (TECAS). To assess the efficacy and safety of TECAS, we compare it with a selective serotonin reuptake inhibitor (SSRI), escitalopram, for the treatment of depression.

Methods/Design

This is a multi-center, non-inferiority, randomized controlled trial that will involve 470 patients with mild to moderate depression. Patients will be randomly assigned to either the TECAS group or the escitalopram group in a 1:1 ratio. The TEAS group will receive two sessions of treatments per day for 8 consecutive weeks, and the escitalopram group will receive 8 weeks of oral escitalopram tablets prescribed by clinical psychiatrists as appropriate for their condition. The primary outcome is the clinical response as determined by Montgomery-Åsberg Depression Rating Scale (MADRS) scores at week 8, with −10% as the non-inferior margin. The secondary outcomes include the response rate determined by 17-item Hamilton Depression Rating Scale (HAMD-17), remission rate, changes from baseline in the scores on the MADRS, the HAMD-17, the Hamilton Anxiety Rating Scale (HAMA), the Pittsburgh Sleep Quality Index (PSQI), and the Short Form 36 Health Survey (SF-36).

Discussion

This will be the first randomized controlled trial to compare the efficacy of TECAS with escitalopram for depression. If effective, this novel intervention could have significant clinical and research implications for patients with depression.

Clinical Trial Registration

[ClinicalTrials.gov], identifier [NCT03909217].
How Impulsiveness Influences Obesity: The Mediating Effect of Resting-State Brain Activity in the dlPFC
Authors: Han Xiao-Dong , Zhang Hong-Wei , Xu Ting , Liu Lin , Cai Hui-Ting , Liu Zi-Qi , Li Qing , Zheng Hui , Xu Tao , Yuan Ti-Fei
Published: May 2022

Impulsiveness is a stable personal characteristic that contributes to obesity and may interact with it. Specifically, obesity is caused by unrestrained impulse eating that is not consciously controlled and leads to a hormonal imbalance that also can impair impulse control. However, the mechanism of this relationship is unclear. In our study, 35 obese individuals (body mass index, BMI > 28) were recruited and matched with 31 healthy controls (BMI < 24) in age and education level. All the participants underwent a resting-state fMRI and completed the Barratt Impulsiveness Scale-11. The results showed that patients with obesity had a significantly lower fractional amplitude of low-frequency fluctuations (fALFF) in the bilateral dorsolateral prefrontal cortex (dlPFC) and higher fALFF in the left fusiform cortex. In addition, non-planning impulsiveness was positively correlated with BMI. Importantly, we found that the right dlPFC completely mediated the relationship between non-planning impulsiveness and BMI. Our findings suggest that impulsivity is statistically more likely to precede obesity than to precede impulsivity and contributes to obesity by downregulating spontaneous activity in the dlPFC. This suggests that the dlPFC, which is associated with executive control, may be able a potential target for treating obesity.
Alterations of Resting-State Locus Coeruleus Functional Connectivity After Transdermal Trigeminal Electrical Neuromodulation in Insomnia
Authors: Um Yoo Hyun , Wang Sheng-Min , Kang Dong Woo , Kim Nak-Young , Lim Hyun Kook
Published: May 2022

Background

Transdermal trigeminal electrical neuromodulation (TTEN) is a novel treatment modality that is known for noradrenergic modulation through the trigeminal nerve and locus coeruleus (LC). This study aimed to demonstrate the alterations of LC functional connectivity (FC) in patients with insomnia after a 4-week TTEN.

Methods

The Cefaly device targeting the ophthalmic division of the trigeminal nerve was applied to a total of 12 patients with insomnia to monitor for the effects of TTEN. All the patients went through a 4-week daily 20 min TTEN sessions before bedtime. Baseline and post-TTEN demographic data, polysomnography (PSG) parameters, and insomnia severity index (ISI) were attained. Data from pre- and post-intervention resting-state functional magnetic resonance imaging (MRI) were collected. LC FC differences were measured between the pre-and post-TTEN groups through seed-to-voxel analysis. Correlation analyses were conducted between LC FC changes after TTEN, ISI score changes, and PSG parameter changes.

Results

There was a significantly decreased LC FC with occipital and temporal cortices after a 4-week TTEN. However, there was no significant correlation between LC FC, ISI score changes, and PSG parameter changes.

Conclusion

By targeting hyperarousal symptoms of insomnia, TTEN can be a promising intervention that can modulate LC FC in patients with insomnia patients. The data presented in the study are from a study exploring the effect of TTEN on insomnia (www.clinicaltrials.gov, NCT04838067).
From Perceived Stress to Demoralization in Parkinson Disease: A Path Analysis
Authors: de Figueiredo John M. , Zhu Boheng , Patel Amar , Kohn Robert , Koo Brian B. , Louis Elan D.
Published: May 2022

Objectives

The objective of this study was to determine whether depression and anxiety are mediators between perceived stress and demoralization via a loss of the cognitive map to get out of the predicament manifesting as subjective incompetence.

Methods

Ninety-five consecutive outpatients with Parkinson's disease were evaluated for perceived stress, depression, anxiety, subjective incompetence, and demoralization using reliable and valid scales. Inclusion criteria were ages 40–90, intact cognition, and no current history of substance use. The setting was a Movement Disorders Clinic at a university-affiliated hospital. The outcome variable was demoralization, selecteda priori. Mediators between perceived stress and demoralization were examined using path analysis.

Results

Depression, anxiety, and subjective incompetence were mediators between perceived stress and demoralization. Among all variables, subjective incompetence was the largest contributor to demoralization. Depression connected to demoralization indirectly via subjective incompetence (β = 0.25,p< 0.001), whereas anxiety bypassed subjective incompetence (β = −0.01,p= 0.882), connecting directly to demoralization (β = 0.37,p= 0.008).

Conclusion

Early treatment and reversal of subjective incompetence and anxiety could potentially prevent the escalation of demoralization and the associated disruption in health-related quality of life and eventual suicide.
Altered White Matter Integrity at Illness Onset in Adolescents With a First Episode of Psychosis
Authors: Romero Soledad , de la Serna Elena , Baeza Inmaculada , Valli Isabel , Pariente José Carlos , Picado Marisol , Bargalló Nuria , Sugranyes Gisela , Castro-Fornieles Josefina
Published: May 2022

Background

Disruption in white matter integrity has been consistently observed in individuals with psychosis. However, whether such abnormalities are already present at illness onset or are related to downstream processes remains elusive. The study of adolescents with a recent onset of psychosis provides the opportunity to evaluate white matter integrity proximally to disease onset.

Methods

Twenty-six adolescents (aged 15.9 ± 1.3 years) with a first episode of psychosis (FEP) (less than 6 months duration) were compared with 26 age and sex-matched healthy controls (HC) (16.8 ± 2 years). In participants with a FEP, clinical diagnoses were confirmed after a minimum of 1 year follow-up (main categories: schizophrenia, bipolar disorder, or schizoaffective disorder). Anatomical images and diffusion tensor sequences were acquired using a 1.5T scanner. Whole brain, voxel-wise group differences in fractional anisotropy (FA) were investigated between participants with a FEP and controls.

Results

Relative to HC, FEP participants displayed decreased FA in the right posterior cingulate gyrus, encompassing the right superior and posterior corona radiata, and the right parahippocampal gyrus, including the cingulum and fornix. FEP patients showed no areas of increased FA relative to HC. The results remained significant after controlling for medication, cannabis use and intelligence.

Conclusion

Our findings indicate that adolescents with recent onset of psychotic disorders show decreased white matter integrity in circuits implicated in cognitive functions and emotion regulation.
Integrated Management of Diabetes and Tuberculosis in Rural India – Results From a Pilot Study
Authors: Joshi Rohina , Behera Deepanjali , Di Tanna Gian Luca , Ameer Mohammed Abdul , Yakubu Kenneth , Praveen Devarsetty
Published: May 2022

Introduction

The World Health Organization and International Union against Tuberculosis (TB) recommends screening patients with TB for Diabetes Mellitus (DM) at the initiation of treatment. There are few pilot studies which screen TB patients for DM, but none of them have documented the feasibility of managing TB patients with DM in the Indian healthcare setting. Operational research is needed to determine the best way to manage individuals with both conditions. This pilot study aimed to develop, and field test an integrated, multidisciplinary program addressing the management of individuals with TB and DM and other associated chronic conditions in the Indian primary healthcare setting.

Methods

This pilot study used a randomized controlled trial design with mixed-methods evaluation and was conducted in Guntur district of Andhra Pradesh, a southern state of India. All the 120 patients newly diagnosed with TB from 10 participating villages were screened for DM and associated cardiovascular risk factors. Non-physician health workers were trained to follow-up patients for a period of 8 months to encourage treatment adherence, monitor treatment response including blood glucose levels and provide lifestyle advice.

Results

The intervention was well-accepted by the providers and patients. However, there were no statistically significant variations observed for mean blood glucose levels (mean [SD]: 5.3 [−23.3 to 33.8]) of patients for both intervention and control group participants in this feasibility study. Awareness about diabetes and tuberculosis comorbidity and cardiovascular risk increased among the non-physician health workers in the intervention arm of the study.

Discussion

The co-management of TB-DM is acceptable to both the health providers and patients. With appropriate training, availability of infrastructure and planned intervention implementation, it is feasible to co-manage TB-DM within the existing primary health care system in India.