bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations in Lysosome Homeostasis in Lipid-Related Disorders: Impact on Metabolic Tissues and Immune Cells
Authors: Cabrera-Reyes Fernanda , Parra-Ruiz Claudia , Yuseff María Isabel , Zanlungo Silvana
Published: December 2021

Lipid-related disorders, which primarily affect metabolic tissues, including adipose tissue and the liver are associated with alterations in lysosome homeostasis. Obesity is one of the more prevalent diseases, which results in energy imbalance within metabolic tissues and lysosome dysfunction. Less frequent diseases include Niemann-Pick type C (NPC) and Gaucher diseases, both of which are known as Lysosomal Storage Diseases (LSDs), where lysosomal dysfunction within metabolic tissues remains to be fully characterized. Adipocytes and hepatocytes share common pathways involved in the lysosome-autophagic axis, which are regulated by the function of cathepsins and CD36, an immuno-metabolic receptor and display alterations in lipid diseases, and thereby impacting metabolic functions. In addition to intrinsic defects observed in metabolic tissues, cells of the immune system, such as B cells can infiltrate adipose and liver tissues, during metabolic imbalance favoring inflammation. Moreover, B cells rely on lysosomes to promote the processing and presentation of extracellular antigens and thus could also present lysosome dysfunction, consequently affecting such functions. On the other hand, growing evidence suggests that cells accumulating lipids display defective inter-organelle membrane contact sites (MCSs) established by lysosomes and other compartments, which contribute to metabolic dysfunctions at the cellular level. Overall, in this review we will discuss recent findings addressing common mechanisms that are involved in lysosome dysregulation in adipocytes and hepatocytes during obesity, NPC, and Gaucher diseases. We will discuss whether these mechanisms may modulate the function of B cells and how inter-organelle contacts, emerging as relevant cellular mechanisms in the control of lipid homeostasis, have an impact on these diseases.
The Imprinted PARAFILM as a New Carrier Material for Dried Plasma Spots (DPSs) Utilizing Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) in Phospholipidomics
Authors: Chen Jiansong , Hu Yue , Shao Congxiang , Zhou Haiyun , Lv Zhiyue
Published: December 2021

The application of desorption electrospray ionization mass spectrometry (DESI-MS) and dried blood spot (DBS) sampling has been successfully implemented several times. However, the difficulty of combining DBS sampling with DESI-MS is still the carrier material used for the blood samples. In this study, a new, easily obtained, and cost-effective carrier substrate for dried plasma spot (DPS) sampling and DESI-MS analysis and its application in phospholipidomics studies was described. First, the effects of several carrier materials, including cellulose-based materials (31 ET paper and filter paper) and non-cellulose-based materials (PARAFILM and its shape-modified material, PTFE-printed glass slide and polyvinylidene fluoride film), were tested. Second, a method combining DPS sampling with DESI-MS for phospholipidomics analysis was established, and parameters affecting compound signal intensities, such as sample volume and sprayer solvent system, were optimized. In conclusion, the total signal intensity obtained from shape-modified PARAFILM was the strongest. The suitable plasma sample volume deposited on PARAFILM carriers was 5 μl, and acetonitrile (ACN) was recommended as the optimal spray solvent for phospholipid (PL) profiling. Repeatability (87.5% of compounds with CV < 30%) and stability for data acquisition (48 h) were confirmed. Finally, the developed method was applied in phospholipidomics analysis of schistosomiasis, and a distinguished classification between control mice and infected mice was observed by using multivariate pattern recognition analysis, confirming the practical application of this new carrier material for DPS sampling and DESI-MS analysis. Compared with a previously reported method, the rapid metabolomics screening approach based on the implementation of DPS sampling coupled with the DESI-MS instrument developed in this study has increased analyte sensitivity, which may promote its further application in clinical studies.
ZIF-8/PI Nanofibrous Membranes With High-Temperature Resistance for Highly Efficient PM0.3 Air Filtration and Oil-Water Separation
Authors: Li Yu , Wang Dan , Xu Guanchen , Qiao Li , Li Yong , Gong Hongyu , Shi Lei , Li Dongwei , Gao Meng , Liu Guoran , Zhang Jingjing , Wei Wenhui , Zhang Xingshuang , Liang Xiu
Published: December 2021

Air and water pollution poses a serious threat to public health and the ecological environment worldwide. Particulate matter (PM) is the major air pollutant, and its primary sources are processes that require high temperatures, such as fossil fuel combustion and vehicle exhaust. PM0.3 can penetrate and seriously harm the bronchi of the lungs, but it is difficult to remove PM0.3 due to its small size. Therefore, PM0.3 air filters that are highly efficient and resistant to high temperatures must be developed. Polyimide (PI) is an excellent polymer with a high temperature resistance and a good mechanical property. Air filters made from PI nanofibers have a high PM removal efficiency and a low air flow resistance. Herein, zeolitic imidazolate framework-8 (ZIF-8) was used to modify PI nanofibers to fabricate air filters with a high specific surface area and filtration efficiency. Compared with traditional PI membranes, the ZIF-8/PI multifunction nanofiber membranes achieved super-high filtration efficiency for ultrafine particles (PM0.3, 100%), and the pressure drop was only 63 Pa. The filtration mechanism of performance improvement caused by the introduction of ZIF-8/PI nanofiber membrane is explored. Moreover, the ZIF-8/PI nanofiber membranes exhibited excellent thermal stability (300 C) and efficient water–oil separation ability (99.85%).
Observer-Based Control of LPV Systems with Input Delay and Saturation and Matched Disturbances via a Generalized Sector Condition
Authors: Salavati Saeed , Grigoriadis Karolos , Franchek Matthew
Published: December 2021

This paper examines the control design for parameter-dependent input-delay linear parameter-varying (LPV) systems with saturation constraints and matched input disturbances. A gain-scheduled dynamic output feedback controller, coupled with a disturbance observer to cancel out input disturbance effects, was augmented with an anti-windup compensator to locally stabilize the input-delay LPV system under saturation, model uncertainty, and exogenous disturbances. Sufficient delay-dependent conditions to asymptotically stabilize the closed-loop system were derived using Lyapunov-Krasovskii functionals and a modified generalized sector condition to address the input saturation nonlinearity. The level of disturbance rejection was characterized via the closed-loop inducedL2-norm of the closed-loop system in the form of linear matrix inequality (LMI) constraints. The results are examined in the context of the mean arterial pressure (MAP) control in the clinical resuscitation of critical hypotensive patients. The MAP variation response to the injection of vasopressor drugs was modeled as an LPV system with a varying input delay and was susceptible to model uncertainty and input/output disturbances. A Bayesian filtering method known as the cubature Kalman filter (CKF) was used to estimate the instantaneous values of the parameters. The varying delay was estimated via a multiple-model approach. The proposed input-delay LPV control was validated in closed-loop simulations to demonstrate its merits and capabilities in the presence of drug administration constraints.
Development and Validation of a Prediction Model for Irreversible Worsened Cardiac Function in Patients With Acute Decompensated Heart Failure
Authors: Wang Lei , Zhao Yun-Tao
Published: December 2021

Background: Irreversible worsening of cardiac function is an adverse event associated with significant morbidity among patients with acute decompensated heart failure (ADHF). We aimed to develop a parsimonious model which is simple to use in clinical settings for the prediction of the risk of irreversible worsening of cardiac function.

Methods: A total of 871 ADHF patients were enrolled in this study. Data for each patient were collected from the medical records. Irreversible worsening of cardiac function included cardiac death within 30-days of patient hospitalization, implantation of a left ventricular assistance device, or emergency heart transplantation. We performed LASSO regression for variable selection to derive a multivariable logistic regression model. Five candidate predictors were selected to derive the final prediction model. The prediction model was verified using C-statistics, calibration curve, and decision curve.

Results: Irreversible worsening of cardiac function occurred in 7.8% of the patients. Advanced age, NYHA class, high blood urea nitrogen, hypoalbuminemia, and vasopressor use were its strongest predictors. The prediction model showed good discrimination C-statistic value, 0.866 (95% CI, 0.817–0.907), which indicated good identical calibration and clinical efficacy.

Conclusion: In this study, we developed a prediction model and nomogram to estimate the risk of irreversible worsening of cardiac function among ADHF patients. The findings may provide a reference for clinical physicians for detection of irreversible worsening of cardiac function and enable its prompt management.
The Transformative Impact of a Mathematical Mindset Experience Taught at Scale
Authors: Boaler Jo , Dieckmann Jack A. , LaMar Tanya , Leshin Miriam , Selbach-Allen Megan , Pérez-Núñez Graciela
Published: December 2021

A wide range of evidence points to the need for students to have a growth mindset as they approach their learning, but recent critiques of mindset have highlighted the need to change teaching approaches, to transfuse mindset ideas throughout teaching. This shifts the responsibility from students themselves to teachers and schools. This paper shares a mixed methods study conducted across the US, that measured the impact of a “mathematical mindset teaching approach” shown to be effective when taught by the authors, scaled to teachers in 10 US districts. The effectiveness of this novel mathematics approach was measured using pre and post assessments during a summer intervention followed by measures of GPA change when students returned to schools. Both measures showed that a mathematical mindset approach to teaching significantly improves students’ mathematical achievement, and changes students’ beliefs about themselves and their approach to learning. Accompanying analyses of teaching and of teacher interviews give insights into the ways students change, highlighting the need to bring about shifts in students’ mindsets through a changed approach to mathematics teaching and learning.
Carbon Emission Trading Policy and Carbon Emission Efficiency: An Empirical Analysis of China’s Prefecture-Level Cities
Authors: Chen Lei , Liu Yining , Gao Yue , Wang Jingjing
Published: December 2021

Improving carbon emission efficiency is an important means to achieve pollution reduction and sustainable economic development. Rather than focusing on the implementation of market-incentive environmental policies in developed countries, we study the effect of the implementation of market-incentive environmental policies on the efficiency of carbon emissions in developing countries, which is generally ignored by frontiers researches. Based on panel data of 282 cities at prefecture-level and above in China from 2007 to 2017, we first adopt the non-radial distance function (NDDF) and global DEA model to measure the carbon emission efficiency of China’s cities. Then we take the Chinese carbon emission trading pilot as a quasi-natural experiment and explore the impact of carbon emission trading policy on carbon emission efficiency based on DID method. And the mechanisms are analyzed through the mediation effect model. It is found that the carbon emission rights trading policy can significantly improve the carbon emission efficiency of the pilot cities, and it mainly plays a role through three channels: technological progress effect, green innovation effect and energy consumption structure optimization effect. The heterogeneity test results show that for resource-based cities and cities with a higher degree of marketization, the carbon emission trading policy has a more obvious effect on improving carbon emission efficiency.
Inter-Specific Variation in the Potential for Upland Rush Management Advocated by Agri-Environment Schemes to Increase Breeding Wader Densities
Authors: Kelly Leah A. , Douglas David J. T. , Shurmer Mike P. , Evans Karl L.
Published: December 2021

Encroachment of rush Juncus spp. in the United Kingdom uplands poses a threat to declining wader populations due to taller, denser swards that can limit foraging and breeding habitat quality for some species. Rush management via cutting, implemented through agri-environment schemes (AESs), could thus increase wader abundance, but there is insufficient assessment and understanding of how rush management influences upland waders. Across two upland regions of England [South West Peak (SWP) and Geltsdale nature reserve, Cumbria], we surveyed waders over four visits in fields where rush was managed according to AES prescriptions (treatment; n = 21) and fields without rush management that were otherwise ecologically similar (control; n = 22) to assess how the densities of breeding wader pairs respond to rush management in the short-term. We find evidence for regional variation in the response of waders to rush management, with densities of Common Snipe Gallinago gallinago significantly higher in treatment than control fields in the SWP, but not Geltsdale. There were no statistically significant responses to treatment on densities of Eurasian Curlew Numenius arquata or Northern Lapwing Vanellus vanellus. The 95% confidence intervals for the treatment parameter estimates suggest that this may be due to limited statistical power in the case of Lapwing. For Curlew, however, any potential increases in densities are negligible. There was no evidence that variation in rush cover, which ranged from 10 to 70%, influenced densities of any of our three focal species. Our results suggest that rush management through AES prescriptions delivered in isolation of other interventions may not lead to general increases in breeding wader densities in the short-term, but benefits may arise in some situations due to regional and inter-specific variation in effectiveness. Rush management supported with interventions that improve soil conditions and thus food availability, or reduce predation pressure, may enable AES rush management to generate benefits. Additional research is required to maximise the potential benefits of rush management for each species through the development of prescriptions that tailor to individual species’ optimum sward structure.
Hereditary Multiple Exostoses—A Review of the Molecular Background, Diagnostics, and Potential Therapeutic Strategies
Authors: Bukowska-Olech Ewelina , Trzebiatowska Wiktoria , Czech Wiktor , Drzymała Olga , Frąk Piotr , Klarowski Franciszek , Kłusek Piotr , Szwajkowska Anna , Jamsheer Aleksander
Published: December 2021

Hereditary multiple exostoses (HMEs) syndrome, also known as multiple osteochondromas, represents a rare and severe human skeletal disorder. The disease is characterized by multiple benign cartilage-capped bony outgrowths, termed exostoses or osteochondromas, that locate most commonly in the juxta-epiphyseal portions of long bones. Affected individuals usually complain of persistent pain caused by the pressure on neighboring tissues, disturbance of blood circulation, or rarely by spinal cord compression. However, the most severe complication of this condition is malignant transformation into chondrosarcoma, occurring in up to 3.9% of HMEs patients. The disease results mainly from heterozygous loss-of-function alterations in the EXT1 or EXT2 genes, encoding Golgi-associated glycosyltransferases, responsible for heparan sulfate biosynthesis. Some of the patients with HMEs do not carry pathogenic variants in those genes, hence the presence of somatic mutations, deep intronic variants, or another genes/loci is suggested. This review presents the systematic analysis of current cellular and molecular concepts of HMEs along with clinical characteristics, clinical and molecular diagnostic methods, differential diagnosis, and potential treatment options.
Praziquantel Treatment of Schistosoma mansoni Infected Mice Renders Them Less Susceptible to Reinfection
Authors: Nono Justin Komguep , Mpotje Thabo , Mosala Paballo , Aziz Nada Abdel , Musaigwa Fungai , Hlaka Lerato , Spangenberg Thomas , Brombacher Frank
Published: December 2021

Beyond transient control of the infection, additional benefits of mass drug administration of praziquantel in endemic communities have been suggested in communities but not mechanistically investigated experimentally. The present study sought to evaluate the additional and hitherto unreported benefits of repeated mass drug administration of praziquantel. We used a tractable mouse model ofSchistosoma mansoniinfection to assess the effects of repeated infection-treatment cycles on the host susceptibility to reinfection. Parasitaemia was assessed by quantification of Schistosoma egg burden in liver tissues and morbidity was followed up by histological observation of liver lesions by microscopy and using biochemical measurement of liver transaminases. Immune responses were further determined by serum probing of schistosoma-specific antibodies, cytokines and quantification of liver cellular and soluble mediator responses by flow cytometry and ELISA, respectively. At similar ages and comparable gender distribution, groups of mice undergoing higher number of infections treatment cycles over a longer period, remained susceptible to reinfection by the parasite, as judged by the presence of eggs and the associated increasing pathology in the liver tissues. However, notably, there was a clear and significantly higher propensity to lower egg burden upon reinfection when compared to counterparts undergoing a lower number of infection-treatment cycles. This relative reduction of susceptibility to infection was paralleled by a more robust humoral response against parasite antigens, elevated serum IL-4 and liver cytokines. Of note, praziquantel treatment of infected mice left them at a higher baseline of serum IL-4, IgE and liver cytokines but lower CD4+ T cell -derived cytokines when compared to infected non-treated mice supporting an immunological treatment-induced advantage of previously infected mice over naïve mice and infected/not treated mice. Notably, repeated infection-treatment cycles did not preclude the infection-driven aggravation of collagen deposition in the livers over time and was corroborated by a more robust local production of inflammatory cytokines in the most exposed livers. Taken together, our data reveal that treatment ofS. mansoni-infected hosts with praziquantel rewires the immune system to a conformation less permissive to subsequent reinfection in mice. Provided the data are translatable from mouse to human, our findings may provide mechanistic support to the potential benefits of more frequent MDAs in high transmission areas to allow rapid acquisition of protective immunity against reinfection.
Seascape Genomics Reveals Metapopulation Connectivity Network of Paramuricea biscaya in the Northern Gulf of Mexico
Authors: Galaska Matthew P. , Liu Guangpeng , West Destiny , Erickson Katie , Quattrini Andrea M. , Bracco Annalisa , Herrera Santiago
Published: December 2021

The degree of connectivity among populations influences their ability to respond to natural and anthropogenic stressors. In marine systems, determining the scale, rate, and directionality of larval dispersal is therefore, central to understanding how coral metapopulations are interconnected and the degree of resiliency in the event of a localized disturbance. Understanding these source-sink dynamics is essential to guide restoration efforts and for the study of ecology and evolution in the ocean. The patterns and mechanisms of connectivity in the deep-sea (>200 m deep) are largely understudied. In this study, we investigated the spatial diversity patterns and metapopulation connectivity of the octocoral Paramuricea biscaya throughout the northern Gulf of Mexico (GoM). Paramuricea biscaya is one of the most abundant corals on the lower continental slope (between 1,200 and 2,500 m) in the GoM. The 2010 Deepwater Horizon oil spill (DWH) directly impacted populations of this species and thus are considered primary targets for restoration. We used a combination of seascape genomic analyses, high-resolution ocean circulation modeling, and larval dispersal simulations to quantify the degree of population structuring and connectivity among P. biscaya populations. Evidence supports the hypotheses that the genetic diversity of P. biscaya is structured by depth, and that larval dispersal among connected populations is asymmetric due to dominant ocean circulation patterns. Our results suggest that there are intermediate unsampled populations in the central GoM that serve as stepping stones for dispersal. The data suggest that the DeSoto Canyon area, and possibly the West Florida Escarpment, critically act as sources of larvae for areas impacted by the DWH oil spill in the Mississippi Canyon. This work illustrates that the management of deep-sea marine protected areas should incorporate knowledge of connectivity networks and depth-dependent processes throughout the water column.
Endoscopic Findings of Gastro-Esophageal Reflux Disease in Elderly and Younger Age Groups
Authors: Adanir Haydar , Baş Bilge , Pakoz Betul , Günay Süleyman , Camyar Hakan , Ustaoglu Muge
Published: December 2021

Objective: To determine and compare the clinical features and endoscopic findings of gastro-esophageal reflux disease (GERD) in elderly and younger age groups.

Materials and Methods: The clinical and endoscopic features were evaluated for all patients with GERD between January 2017 and September 2020. The criteria for inclusion were being aged over 65 and under 50 years and having an upper gastrointestinal endoscopy with reflux symptoms resistant to ppi theraphy. The exclusion criteria included prior surgery, age under 18 years, and pregnancy. The diagnosis of GERD was made according to the patients' symptoms. The SPSS 11.0 for Windows pocket program was used for statistical analysis.

Results: Two hundred eighty-six patients aged over 65 years and 261 patients aged below 50 years were enrolled in this study. The mean age of the older group was 68.2 ± 4.5 years and the mean age of the young group was 38 ± 7.2 years. The male/female ratio was 5/3 and 2/1 in the young and older groups, respectively. The older patients had less severe and rare typical symptoms than the young patients. However, significantly more serious endoscopic findings were noted in the older patients compared with the younger patients.

Conclusion: The older and young patients with GERD were predominantly male and typical reflux problems were less common in older patients with GERD. Older patients had more important endoscopic findings such as hernia, esophagitis, and cancer.
Associations Between Diabetic Retinal Microvasculopathy and Neuronal Degeneration Assessed by Swept-Source OCT and OCT Angiography
Authors: Qiu Bingjie , Zhao Lin , Zhang Xinyuan , Wang Yanhong , Wang Qiyun , Nie Yao , Chen Xiaosi , Cheung Carol Y. L.
Published: December 2021

Purpose: To provide clinical evidence of the associations between retinal neuronal degeneration and microvasculopathy in diabetic retinopathy (DR).

Methods: This case-control study included 76 patients (76 eyes) with type 2 diabetes mellitus (DM), and refraction error between −3.0 and +3.0 D. The eyes were assigned into DM (without DR), non-proliferative DR (NPDR), and proliferative DR (PDR) groups. Age-, sex-, and refractive error-matched normal subjects were enrolled as controls. The mean retinal thickness (mRT), the relative mean thickness of the retinal nerve fiber layer (rmtRNFL, mtRNFL/mRT), ganglion cell layer (rmtGCL), ganglion cell complex (rmtGCC) layer, foveal avascular zone area (FAZa), FAZ perimeter (FAZp), FAZ circularity index (FAZ-CI), and vessel density (VD) in superficial capillary plexus (SCP) and deep capillary plexus (DCP) were assessed by swept-source optical coherence tomography (OCT) and OCT angiography (OCTA). Group comparison and Spearman's partial correlation coefficient analysis were applied to evaluate the correlation between these morphological parameters.

Results: rmtRNFL, FAZa, and FAZp in SCP and DCP increased with the DR severity (prmtRNFL < 0.001; pFAZa, SCP = 0.001; pFAZa, DCP = 0.005; pFAZp, SCP < 0.001; pFAZp, DCP < 0.001). The rmtGCL, FAZ-CI in SCP and DCP, and VD in DCP decreased with the DR severity (prmtGCL = 0.002, pFAZ−CI, SCP = 0.002; pFAZ−CI, DCP < 0.001, pVD, DCP < 0.001). After controlling age, sex, duration of diabetes, and hypertension, the rmtRNFL, FAZa in SCP and DCP, and FAZp in SCP and DCP were correlated with the severity of DR (p < 0.05), while VD in SCP and DCP, FAZ-CI, and rmtGCL were negatively correlated with the severity of DR (p < 0.05). The rmtGCL was negatively correlated with the FAZa in SCP (r = −0.34, p = 0.002) and DCP (r = −0.23, p = 0.033), and FAZp in SCP (r = −0.37, p = 0.001) and DCP (r = −0.32, p = 0.003), but positively correlated with VD in SCP (r = 0.26, p = 0.016), VD in DCP (r = 0.28, p = 0.012), and FAZ-CI in DCP (r = 0.31, p = 0.006).

Conclusions: rmtRNFL, FAZ-CI in SCP and DCP, and FAZp in SCP are strong predictors of the severity of DR. The ganglion cell body loss is highly correlated with increased FAZp and FAZa, decreased FAZ-CI, and reduced VD with the severity of DR.
Quorum Sensing Regulates the Hydrolytic Enzyme Production and Community Composition of Heterotrophic Bacteria in Coastal Waters
Authors: Urvoy Marion , Lami Raphaël , Dreanno Catherine , Delmas Daniel , L’Helguen Stéphane , Labry Claire
Published: December 2021

Heterotrophic microbial communities play a central role in biogeochemical cycles in the ocean by degrading organic matter through the synthesis of extracellular hydrolytic enzymes. Their hydrolysis rates result from the community’s genomic potential and the differential expression of this genomic potential. Cell-cell communication pathways such as quorum sensing (QS) could impact both aspects and, consequently, structure marine ecosystem functioning. However, the role of QS communications in complex natural assemblages remains largely unknown. In this study, we investigated whetherN-acylhomoserine lactones (AHLs), a type of QS signal, could regulate both hydrolytic activities and the bacterial community composition (BCC) of marine planktonic assemblages. To this extent, we carried out two microcosm experiments, adding five different AHLs to bacterial communities sampled in coastal waters (during early and peak bloom) and monitoring their impact on enzymatic activities and diversity over 48 h. Several specific enzymatic activities were impacted during both experiments, as early as 6 h after the AHL amendments. The BCC was also significantly impacted by the treatments after 48 h, and correlated with the expression of the hydrolytic activities, suggesting that changes in hydrolytic intensities may drive changes in BCC. Overall, our results suggest that QS communication could participate in structuring both the function and diversity of marine bacterial communities.
Identification, Characterization, and Evaluation of Nematophagous Fungal Species of Arthrobotrys and Tolypocladium for the Management of Meloidogyne incognita
Authors: Kassam Rami , Yadav Jyoti , Chawla Gautam , Kundu Aditi , Hada Alkesh , Jaiswal Nisha , Bollinedi Haritha , Kamil Deeba , Devi Prameela , Rao Uma
Published: December 2021

Root-knot nematodes belonging to the genus Meloidogyne are agriculturally important pests, and biocontrol strategies offer safer alternatives for their management. In the present study, two fungal species from Indian soils were identified as Arthrobotrys thaumasia and Tolypocladium cylindrosporum based on morphological characteristics and further confirmed using molecular markers. In vitro evaluation of A. thaumasia against M. incognita and Caenorhabditis elegans showed 82 and 73% parasitism, respectively, whereas T. cylindrosporum gave 65.2 and 57.7% parasitism, respectively. Similarly, culture filtrates of A. thaumasia caused 57.7 and 53.7% mortality of M. incognita and C. elegans, respectively, whereas T. cylindrosporum caused higher mortality of 87.3 and 64%, respectively. Besides, greenhouse evaluation of both fungi against M. incognita infecting tomato significantly reduced nematode disease burden reflecting parasitic success measured as the total number of galls, egg masses, eggs per egg mass, and derived nematode multiplication factor. Application of A. thaumasia and T. cylindrosporum reduced nematode multiplication factor by 80 and 95%, respectively, compared with control. General metabolite profiling of tested fungi using gas chromatography–mass spectrometry and ultra-performance liquid chromatography–quadrupole/time of flight mass spectrometry reported for the first time here showed presence of various volatile and non-volatile compounds with nematicidal activity, viz., trimethyl-heptadiene, methyl-hexadecanol, dodecadienal, decane, terpendole E, dodecane, acetamido-6-anthraquinone, and hexadecanol. Also, other compounds such as undecane, dibutyl-disulfide, octadecenal, paganin, talathermophilin, dactylarin, tolypyridone A, tolypyridone B, pyridoxatin, and destruxin were identified, reported in the literature to possess antibacterial, antifungal, and insecticidal properties. This is the first report of the occurrence of both fungi from India and pioneer demonstration of T. cylindrosporum for root-knot nematode management.
Impact of the Glycemic Level on the Salivary Proteome of Middle-Aged and Elderly People With Type 2 Diabetes Mellitus: An Observational Study
Authors: Jia Shu Yuan , Zhang Yan Ling , Sun Xiang Yu , Yuan Chao , Zheng Shu Guo
Published: December 2021

Type 2 diabetes mellitus (T2DM) is an increasing global public health concern, but its impact on the salivary proteome is still unclear. To evaluate the effect of glycemic levels in middle-aged and elderly individuals with T2DM on salivary proteomics, we compared the differences by liquid chromatography tandem mass spectrometry (LC–MS/MS). Unstimulated whole saliva samples from 8 T2DM patients with good glycemic control (G group, HbA1c <6.5%) and 16 patients with poor control (P group, HbA1c ≥6.5%) were analyzed by LC–MS/MS in the data-independent acquisition mode (Clinical register number: ChiCTR1900023582.). After functional annotation, cluster analysis and receiver operating characteristic (ROC) curve analysis were carried out to screen and evaluate candidate proteins. A total of 5,721 proteins were quantified, while 40 proteins differed significantly. In the P group, proteins involved in oxidative stress-related processes were upregulated, whereas proteins related to salivary secretion were downregulated. The combination of thioredoxin domain-containing protein 17, zymogen granule protein 16B, and FAM3 metabolism regulating signaling molecule D yielded an area under the curve of 0.917 which showed a robust ability to distinguish the P and G groups. In conclusion, poorly controlled hyperglycemia may affect salivary proteins through various pathways, including oxidative stress and glandular secretion. Furthermore, the differentially expressed proteins, especially the three proteins with the best differentiation, might serve as an anchor point for the further study of hyperglycemia and oral diseases.
Maternal Separation Induces Sex-Specific Differences in Sensitivity to Traumatic Stress
Authors: Knox Dayan , Stout-Oswald Stephanie A. , Tan Melissa , George Sophie A. , Liberzon Israel
Published: December 2021

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder with a high economic burden. Two risk factors for increasing the chances of developing PTSD are sex (being female) and early life stress. These risk factors suggest that early life stress-induced changes and sex differences in emotional circuits and neuroendocrinological systems lead to susceptibility to traumatic stress. Exploring mechanisms via which stress leads to specific effects can be accomplished in animal models, but reliable animal models that allow for an examination of how early life stress interacts with sex to increase susceptibility to traumatic stress is lacking. To address this, we examined the effects of early life stress [using the maternal separation (MS) model] and late adolescence/early adult traumatic stress [using the single prolonged stress (SPS) model] on startle reactivity, anxiety-like behavior in the open field (OF), and basal corticosterone levels in male and female rats. Female rats exposed to MS and SPS (MS/SPS) showed enhanced startle reactivity relative to MS/control female rats. Enhanced startle reactivity was not observed in MS/SPS male rats. Instead, non-maternally separated male rats that were exposed to SPS showed enhanced startle reactivity relative to controls. Female rats had enhanced locomotor activity in the OF and higher basal corticosterone levels in comparison to males, but measures in the OF and basal corticosterone were not affected by MS or SPS. Overall the results suggest that the combined MS and SPS models can be used to explore how changes in maternal care during infancy lead to sex differences in sensitivity to the effects of traumatic stress as adolescents and adults.
Striatonigrostriatal Spirals in Addiction
Authors: Sivils Andy , Wang John Q. , Chu Xiang-Ping
Published: December 2021

A biological reward system is integral to all animal life and humans are no exception. For millennia individuals have investigated this system and its influences on human behavior. In the modern day, with the US facing an ongoing epidemic of substance use without an effective treatment, these investigations are of paramount importance. It is well known that basal ganglia contribute to rewards and are involved in learning, approach behavior, economic choices, and positive emotions. This review aims to elucidate the physiological role of striatonigrostriatal (SNS) spirals, as part of basal ganglia circuits, in this reward system and their pathophysiological role in perpetuating addiction. Additionally, the main functions of neurotransmitters such as dopamine and glutamate and their receptors in SNS circuits will be summarized. With this information, the claim that SNS spirals are crucial intermediaries in the shift from goal-directed behavior to habitual behavior will be supported, making this circuit a viable target for potential therapeutic intervention in those with substance use disorders.
Zonisamide for the Efficacy of Sleep Abnormality in Parkinson's Disease (ZEAL Study): A Protocol for Randomized Controlled Trials
Authors: Kataoka Hiroshi , Isogawa Masahiro , Inoue Takashi , Hasebe Miyoko , Takashima Ryuzo , Kasama Shu , Nanaura Hitoki , Kiriyama Takao , Kasahara Masato , Sugie Kazuma
Published: December 2021

Background:Sleep disorders are one of the most frequent non-motor symptoms of Parkinson's disease (PD), and the efficacy of dopaminergic agents remains controversial. Clinical randomized control trials for the treatment of sleep disorders in PD are limited. Zonisamide (1,2-benzisoxazole-3-methanesulfonamide) improved motor symptoms and wearing-off in patients with PD. Patients with PD were reported to have dream-enacting behavior that was resolved after treatment with zonisamide. This study aimed to verify the safety and efficacy of zonisamide for sleep disorders and rapid eye movement (REM) sleep behavioral disorders using a mobile two-channel electroencephalography (EEG)/electrooculography (EOG) recording system.

Methods and Analysis:The present study is a randomized placebo-controlled trial to determine the efficacy of zonisamide for sleep disorders in patients with PD. This study was designed to be single-blind, but the subject allocation is randomized by an independent allocation manager via computer-generated block randomization. The subjects in the treatment group took zonisamide (25 mg per day) before bedtime for 28 days. The sleep index is analyzed using a portable EEG/EOG recording system collected on two consecutive nights within 7 days prior to the intervention and reobtained on one night within 2 days after the 28-day administration of zonisamide. The amount of change in sleep efficiency before and after the 28-day administration will be compared between the zonisamide treatment group and placebo group concerning the primary endpoint. As for the secondary endpoint, the change in the ratio of other sleep parameters, including REM sleep without atonia, or sleep architecture will be evaluated.

Ethics and Dissemination:The protocol was approved by the Nara Medical University Certified Review Board (CRB5200002). The trial was notified and registered with the Japan Registry of Clinical Trials (jRCTs051200160). Written informed consent will be obtained from every participant using informed consent approved by the CRB. The results of this trial will be disseminated through peer-reviewed scientific journals.
Neurological Sequela of Acute Pesticide Poisoning Among Adults in Central Taiwan
Authors: Chen Yen-Chung , Lin Chin-Hsien , Wu Shey-Lin
Published: December 2021

Background and Purpose: Cases of acute pesticide poisoning account for significant morbidity and mortality in developing countries; however, its burden in Taiwan remains unknown. The study examined acute pesticide poisoning (APP) involving adults in the central region of Taiwan, which is a mainly agricultural sub-urban area.

Methods: The retrospective study evaluated the outcome and neurological sequelae of patients with APP in a Taiwanese cohort between April 2002 and February 2019. The pesticides were classified according to the Insecticide Resistance Action Committee Mode of Action (MoA) classification. The clinical characteristics, duration of hospitalization (days), follow-up duration (years), in-hospital mortality, neurological sequela, and imaging findings were recorded. Furthermore, multivariate logistic regression analyses were performed.

Results: We identified 299 patients with APP comprising 206 (68.9%) adult men with a mean exposure age of 56.4 ± 16.8 years. Paraquat, organophosphates, pyrethroids, carmabates, and phosphinic acid were the most commonly known reported poisoning agents. The mortality rate was highest in users with paraquat (77.1%), followed by phosphinic acid (22.2%), carbamates (16.7%), and organophosphates (15.8%). After a mean follows up of 3.69 ± 2.26 years, the most common neurological sequela was a cognitive decline (56 among 225 survivors, 24.89%), peripheral neuropathy (11 among 225 survivors, 4.89%), tremor (10 among 225 survivors, 4.44%), ataxia (3/225, 1.33%), and parkinsonism feature (2/225, 0.89%). Brain imaging studies revealed basal ganglion lesions on CT or hyperintensity on T2-weighted MRI images in 26 among 46 patients (56.5%). The basal ganglion lesions on brain imaging had a positive correlation with neurological sequelae.

Conclusion: Acute pesticide poisoning (APP)-related mortality is high especially paraquat intoxication, and cognitive decline, as well as peripheral neuropathy, were the most common neurological sequelae among survivors, which is highly correlated with basal ganglia lesions on brain imaging.
A Process-Oriented View of Procedural Memory Can Help Better Understand Tourette’s Syndrome
Authors: Farkas Bence Cs. , Tóth-Fáber Eszter , Janacsek Karolina , Nemeth Dezso
Published: December 2021

Tourette’s syndrome (TS) is a neurodevelopmental disorder characterized by repetitive movements and vocalizations, also known as tics. The phenomenology of tics and the underlying neurobiology of the disorder have suggested that the altered functioning of the procedural memory system might contribute to its etiology. However, contrary to the robust findings of impaired procedural memory in neurodevelopmental disorders of language, results from TS have been somewhat mixed. We review the previous studies in the field and note that they have reported normal, impaired, and even enhanced procedural performance. These mixed findings may be at least partially be explained by the diversity of the samples in both age and tic severity, the vast array of tasks used, the low sample sizes, and the possible confounding effects of other cognitive functions, such as executive functions, working memory or attention. However, we propose that another often overlooked factor could also contribute to the mixed findings, namely the multiprocess nature of the procedural system itself. We propose that a process-oriented view of procedural memory functions could serve as a theoretical framework to help integrate these varied findings. We discuss evidence suggesting heterogeneity in the neural regions and their functional contributions to procedural memory. Our process-oriented framework can help to deepen our understanding of the complex profile of procedural functioning in TS and atypical development in general.
Reduced White Matter Integrity in Patients With End-Stage and Non-end-Stage Chronic Kidney Disease: A Tract-Based Spatial Statistics Study
Authors: Jiang Yuhan , Gao Qiuyi , Liu Yangyingqiu , Gao Bingbing , Che Yiwei , Lin Liangjie , Jiang Jian , Chang Peipei , Song Qingwei , Wang Weiwei , Wang Nan , Miao Yanwei
Published: December 2021

Background and Purpose: Reduced white matter (WM) integrity has been implicated in chronic kidney disease (CKD), especially in end-stage renal disease (ESRD). However, whether the differences in WM abnormalities exist in ESRD and non-end-stage CKD (NES-CKD) remains unclear. Hence, this study aimed to investigate the WM microstructural changes between the two stages using diffusion tensor imaging (DTI) and explore the related influencing factors.

Methods: Diffusion tensor imaging’ images were prospectively acquired from 18 patients with ESRD, 22 patients with NES-CKD, and 19 healthy controls (HCs). Tract-based spatial statistics (TBSS) was performed to assess the voxel-wise differences in WM abnormalities among the three groups. The relationships between DTI parameters and biochemical data were also analyzed.

Results: Compared with NES-CKDs, FA value was significantly decreased, and AD value increased in ESRDs mainly in brain regions of bilateral anterior thalamic radiation (ATR), the genu and body of corpus callosum (CC), bilateral anterior corona radiata, superior corona radiata, and superior longitudinal fasciculus. Besides, extensive and symmetrical deep WM damages were observed in patients with ESRD, accompanied by increased MD and RD values. Multiple regression analysis revealed that uric acid and serum phosphorus level can be used as independent predictors of WM microstructural abnormalities in clusters with statistical differences in DTI parameters between ESRD and NES-CKD groups.

Conclusion: In the progression of CKD, patients with ESRD have more severe WM microstructural abnormalities than NES-CKDs, and this progressive deterioration may be related to uric acid and phosphate levels.
Effects of Combining Online Anodal Transcranial Direct Current Stimulation and Gait Training in Stroke Patients: A Systematic Review and Meta-Analysis
Authors: Mitsutake Tsubasa , Imura Takeshi , Hori Tomonari , Sakamoto Maiko , Tanaka Ryo
Published: December 2021

Objective: Combining transcranial direct current stimulation (tDCS) and repetitive gait training may be effective for gait performance recovery after stroke; however, the timing of stimulation to obtain the best outcomes remains unclear. We performed a systematic review and meta-analysis to establish evidence for changes in gait performance between online stimulation (tDCS and repetitive gait training simultaneously) and offline stimulation (gait training after tDCS).

Methods: We comprehensively searched the electronic databases Medline, Cochrane Central Register of Controlled Trials, Physiotherapy Evidence Database, and Cumulative Index to Nursing and Allied Health Literature, and included studies that combined cases of anodal tDCS with motor-related areas of the lower limbs and gait training. Nine studies fulfilled the inclusion criteria and were included in the systematic review, of which six were included in the meta-analysis.

Result: The pooled effect estimate showed that anodal tDCS significantly improved the 10-m walking test (p = 0.04; I2 = 0%) and 6-min walking test (p = 0.001; I2 = 0%) in online stimulation compared to sham tDCS.

Conclusion: Our findings suggested that simultaneous interventions may effectively improve walking ability. However, we cannot draw definitive conclusions because of the small sample size. More high-quality studies are needed on the effects of online stimulation, including various stimulation parameters.
Neuronal Activity Patterns Regulate Brain-Derived Neurotrophic Factor Expression in Cortical Cells via Neuronal Circuits
Authors: Miyasaka Yumi , Yamamoto Nobuhiko
Published: December 2021

During development, cortical circuits are remodeled by spontaneous and sensory-evoked activity via alteration of the expression of wiring molecules. An intriguing question is how physiological neuronal activity modifies the expression of these molecules in developing cortical networks. Here, we addressed this issue, focusing on brain-derived neurotrophic factor (BDNF), one of the factors underlying cortical wiring. Real-time imaging of BDNF promoter activity in organotypic slice cultures revealed that patterned stimuli differentially regulated the increase and the time course of the promoter activity in upper layer neurons. Calcium imaging further demonstrated that stimulus-dependent increases in the promoter activity were roughly proportional to the increase in intracellular Ca2+ concentration per unit time. Finally, optogenetic stimulation showed that the promoter activity was increased efficiently by patterned stimulation in defined cortical circuits. These results suggest that physiological stimulation patterns differentially tune activity-dependent gene expression in developing cortical neurons via cortical circuits, synaptic responses, and alteration of intracellular calcium signaling.
Documentation of the Development of Various Visuomotor Responses in Typically Reared Kittens and Those Reared With Early Selected Visual Exposure by Use of a New Procedure
Authors: MacNeill Katelyn , Myatt Amber , Duffy Kevin R. , Mitchell Donald E.
Published: December 2021

A new procedure was used to study the development of gaze (responses to moving targets or laser spots in normal kittens, those that had been reared in total darkness to 6 weeks of age, and others that received a period of monocular deprivation (MD). Gaze responses were observed to all stimuli in normal kittens at between 25–30 days of age and striking responses occurred on the same day or the next. Despite slow acquisition of spatial vision in the dark reared kittens over 3 months, they were able to follow and even strike at moving visual stimuli within a day of their initial exposure to light. By contrast, for a week following a period of MD, kittens showed no gaze or striking responses to moving stimuli when using their previously deprived eye. The very different profiles of acquisition of visuomotor skills and spatial vision in visually deprived kittens point to a dissociation between the neuronal populations that support these functions.