bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subfield‐specific effects of chronic mild unpredictable stress on hippocampal astrocytes
Authors: Virmani Garima , D'almeida Priyal , Nandi Arnab , Marathe Swananda 
Published: April 2021

AbstractMajor depressive disorder (MDD) is a debilitating neuropsychiatric illness affecting over 20% of the population worldwide. Despite its prevalence, our understanding of its pathophysiology is severely limited, thus hampering the development of novel therapeutic strategies. Recent advances have clearly established astrocytes as major players in the pathophysiology, and plausibly pathogenesis, of major depression. In particular, astrocyte density in the hippocampus is severely diminished in MDD patients and correlates strongly with the disease outcome. Moreover, astrocyte densities from different subfields of the hippocampus show varying trends in terms of their correlation to the disease outcome. Given the central role that hippocampus plays in the pathophysiology of depression and in the action of antidepressant drugs, changes in hippocampal astrocyte density and physiology may have a significant effect on behavioral symptoms of MDD. In this study, we used chronic mild unpredictable stress (CMUS) in mice, which induces a depressive‐like state, and examined its effects on astrocytes from different subfields of the hippocampus. We used SOX9 and S100β immunostaining to estimate the number of astrocytes per square millimeter from various hippocampal subfields. Furthermore, using confocal images of fluorescently labeled glial fibrillary acidic protein (GFAP)‐immunopositive hippocampal astrocytes, we quantified various morphology‐related parameters and performed Sholl analysis. We found that CMUS exerts differential effects on astrocyte cell numbers, ramification, cell radius, surface area, and process width of hippocampal astrocytes from different hippocampal subfields. Taken together, our study reveals that chronic stress does not uniformly affect all hippocampal astrocytes; but exerts its effects differentially on different astrocytic subpopulations within the hippocampus.
Intracerebral electrical stimulation to understand the neural basis of human face identity recognition
Authors: Jonas Jacques , Rossion Bruno 
Published: April 2021

AbstractRecognizing people's identity by their faces is a key function in the human species, supported by regions of the ventral occipito‐temporal cortex (VOTC). In the last decade, there have been several reports of perceptual face distortion during direct electrical stimulation (DES) with subdural electrodes positioned over a well‐known face‐selective VOTC region of the right lateral middle fusiform gyrus (LatMidFG; i.e., the “Fusiform Face Area”, FFA). However, transient impairments of face identity recognition (FIR) have been extremely rare and only behaviorally quantified during DES with intracerebral (i.e., depth) electrodes in stereo‐electroencephalography (SEEG). The three detailed cases reported so far, summarized here, were specifically impaired at FIR during DES inside different anatomical VOTC regions of the right hemisphere: the inferior occipital gyrus (IOG) and the LatMidFG, as well as a region that lies at the heart of a large magnetic susceptibility artifact in functional magnetic resonance imaging (fMRI): the anterior fusiform gyrus (AntFG). In the first two regions, the eloquent electrode contacts were systematically associated with the highest face‐selective and (unfamiliar) face individuation responses as measured with intracerebral electrophysiology. Stimulation in the right AntFG did not lead to perceptual changes but also caused an inability to remember having been presented face pictures, as if the episode was never recorded in memory. These observations support the view of an extensive network of face‐selective VOTC regions subtending human FIR, with at least three critical nodes in the right hemisphere associated with differential intrinsic and extrinsic patterns of reentrant connectivity.
Priority knowledge needs for management of migratory fish species in Cambodia
Authors: Loury Erin K. , Elliott Vittoria L. , Ainsley Shaara M. , Baird Ian G. , Baumgartner Lee J. , Chhuoy Samol , Lee Dana J. , Ngor Peng Bun , Touch Bunthang , Vu An V. , Hogan Zeb S. 
Published: April 2021

AbstractDespite their economic and ecological importance, migratory fishes of the Lower Mekong Basin (LMB) remain understudied, which hampers effective management to sustain valuable fisheries and address serious threats such as habitat degradation, development and overharvest. From a list of potential knowledge needs, a group of fisheries professionals most frequently identified six top priorities for managing migratory fishes in Cambodia: (1) population abundances and trends, (2) life cycles and life history, (3) migration timing and triggers, (4) migration routes and distances, (5) locations of key habitats and spawning areas, and (6) environmental and habitat requirements. These needs are discussed along with nine relevant methodologies for addressing them, including fisheries‐dependent and fisheries‐independent sampling, reproductive techniques and captive studies, otolith and genetic analysis tools, and tagging and imaging techniques. A suggested research framework is also presented to inform adaptive management of migratory fishes. While emphasis is given to Cambodia, the analysis is also applicable to other LMB countries, given that migratory fishes occur throughout the basin and migrate across borders. It is suggested that a robust research and monitoring agenda is required to prioritise knowledge needs and select appropriate methodologies to answer questions vital to inform sustainable migratory fish management in Cambodia.
Evaluating Lower Computational Burden Approaches for Calibration of Large Environmental Models
Authors: Hunt Randall J. , White Jeremy T. , Duncan Leslie L. , Haugh Connor J. , Doherty John 
Published: April 2021

AbstractRealistic environmental models used for decision making typically require a highly parameterized approach. Calibration of such models is computationally intensive because widely used parameter estimation approaches require individual forward runs for each parameter adjusted. These runs construct a parameter‐to‐observation sensitivity, or Jacobian, matrix used to develop candidate parameter upgrades. Parameter estimation algorithms are also commonly adversely affected by numerical noise in the calculated sensitivities within the Jacobian matrix, which can result in unnecessary parameter estimation iterations and less model‐to‐measurement fit. Ideally, approaches to reduce the computational burden of parameter estimation will also increase the signal‐to‐noise ratio related to observations influential to the parameter estimation even as the number of forward runs decrease. In this work a simultaneous increments, an iterative ensemble smoother (IES), and a randomized Jacobian approach were compared to a traditional approach that uses a full Jacobian matrix. All approaches were applied to the same model developed for decision making in the Mississippi Alluvial Plain, USA. Both the IES and randomized Jacobian approach achieved a desirable fit and similar parameter fields in many fewer forward runs than the traditional approach; in both cases the fit was obtained in fewer runs than the number of adjustable parameters. The simultaneous increments approach did not perform as well as the other methods due to inability to overcome suboptimal dropping of parameter sensitivities. This work indicates that use of highly efficient algorithms can greatly speed parameter estimation, which in turn increases calibration vetting and utility of realistic models used for decision making.
Validation of factor VIII activity for monitoring standard and extended half‐life products and correlation to thrombin generation assays
Authors: Augustsson Cecilia , Norström Eva , Lind Vivian , Martin Myriam , Astermark Jan , Strandberg Karin 
Published: April 2021

AbstractIntroductionMonitoring replacement therapy with standard and extended half‐life (EHL) products is challenging, since one‐stage assay (OSA) and chromogenic substrate assay (CSA) results may differ significantly. Recent recommendations include local validation of each new product with recovery within 20–30%, depending on activity level.AimTo validate factor VIII (FVIII) activity for monitoring products in clinical use on Atellica Coag and to correlate it with thrombin generation.MethodsPlasma samples spiked with Advate®, Elocta®, Adynovi®, Nuwiq®, NovoEight® and Afstyla® (0.05, 0.20, 0.50 and 0.80 IU/ml) were analysed using Atellica Coag 360 with CSA‐1 (Coatest SP) and CSA‐2 (FVIII chromogenic), and OSA (Actin FS). Thrombin generation was performed using two thrombin generation assays (TGA‐1 (Thrombinoscope) and TGA‐2 (Technothrombin).ResultsAll products at levels above 0.05 IU/ml, except Adynovi, showed acceptable recovery using CSA‐1, whereas measurements using CSA‐2 gave more results outside the target level. All products, except Afstyla, showed acceptable recovery using OSA. Correlation between CSA‐1 and OSA was excellent (r2=1.0) with biases of 6–3​2%, depending on FVIII product. A clear dose‐response was seen for all thrombin generation parameters and products using both methods, except at low levels for lag time using TGA‐1. With CSA‐1 as an independent variable, the correlations to thrombin peak (measured with TGA‐2) were good (r2 = .8–.9).ConclusionOur data revealed good correlation and acceptable bias between CSA and OSA using our sets of reagents, methods and analyser in spiked samples. Thrombin generation gave good correlation to CSA‐1 factor activity and is a possible complement to factor activity assays.
An evaluation of PROMIS health domains in adults with haemophilia: A cross‐sectional study
Authors: Barry Vaughn , Buckner Tyler W. , Lynch Mary Ellen , Figueroa Janet , Mattis Shanna , Stout Mary E. , Kempton Christine L. 
Published: April 2021

AbstractIntroductionThe Patient‐Reported Outcomes Measurement Information System (PROMIS) provides measures of health status that assess physical, mental and social well‐being from the patient perspective. PROMIS measures are used in clinical practice and research across various patient populations but are not yet validated among patients with haemophilia.AimEvaluate the sensitivity of PROMIS to indicators of haemophilia clinical severity and compare PROMIS measures to those from other PRO instruments.MethodsMale adults with haemophilia (n = 115) completed the PROMIS‐29 short form which includes 4 questions for each of 7 domains: depression, anxiety, ability to participate in social roles and activities, physical function, pain interference, fatigue and sleep disturbance. Participant responses for each domain were scored on a T‐score metric with a mean of 50 and a standard deviation of 10 based on the original PROMIS reference sample of US adults. Participants also completed other generic and haemophilia‐specific health‐related quality of life questionnaires.ResultsParticipants who experienced higher pain and depression levels reported significantly worse health in every PROMIS domain compared with their peers. Those who had recently needed to use crutches, visit an emergency department or were currently unemployed or disabled also reported poor PROMIS scores on most domains. Construct validity was supported by correlations between PROMIS domain scores and domain scores reported using the EQ‐5D‐5L and Haem‐A‐QoL.ConclusionThe PROMIS instrument provides a potentially valuable tool to evaluate the impact of haemophilia and suggests usefulness in research and clinical practice.
The significance of focally enhanced gastritis in haematopoietic stem cell transplant recipients
Authors: Johncilla Melanie , Elsoukkary Sarah , Jessurun Jose 
Published: April 2021

AimsThe histological diagnosis of acute gastric graft‐versus‐host‐disease (aGVHD) in patients with a history of haematopoietic stem cell transplant (HSCT) is based on the presence of epithelial cell apoptosis and karyorrhectic debris. There is, however, limited information on the histological findings in patients who develop symptoms several months after transplant. Focally enhanced gastritis (FEG), defined by the presence of focal periglandular lymphohistiocytic inflammation with neutrophilic or lymphocytic intra‐epithelial infiltration of gastric glands, has been described in patients with inflammatory bowel disease and in HSCT patients. The pattern closely resembles the focal periductal inflammation and lymphocytic exocytosis seen in chronic GVHD of the salivary gland. We sought to evaluate the significance of FEG in HSCT patients.Methods and resultsGastric biopsies from 151 HSCT patients who underwent endoscopies for GVHD‐like symptoms were identified. Time from transplant to biopsy, presence of extra‐gastric GVHD, medications and outcome were noted. Thirty‐five biopsies showed FEG and 21 showed aGVHD; the remainder were either normal or showed non‐specific changes. Twenty‐one (60%) FEG patients had concurrent histologically proven extra‐gastric GVHD. The time to biopsy in FEG patients was significantly longer than in aGVHD patients (162 versus 57 days, P < 0.01). Prior or subsequent gastric biopsies of 14 patients in the FEG cohort were also evaluated and, of these, six showed aGVHD while one showed persistent FEG.ConclusionsThese findings suggest that FEG probably represents a form of late‐occurring GVHD. This histological pattern should not be overlooked when identified in gastric biopsies from HSCT patients.
A randomized clinical study to examine the oral hygiene efficacy of a novel herbal toothpaste with zinc over a 6‐month period
Authors: Nandlal B. , Sreenivasan Prem K. , Shashikumar Pratibha , Devishree G. , Bettahalli Shivamallu Avinash 
Published: April 2021

AbstractObjectivesThis clinical investigation examined the effects of brushing with a test toothpaste containing natural ingredients, that is, clove (Syzgium Aromaticum), aloe vera (Aloe Barbadensis), amla (Emblica Officinalis), neem (Azadirachta Indica), tulsi (Ocimum Basillicum) and honey (from Apis Mellifera) along with zinc salts and fluoride in comparison with a dentifrice formulated with fluoride alone on dental plaque and gingivitis over a 6‐month period.Materials and MethodOne hundred and eighty (180) subjects with mean plaque index scores greater than 1.5 (Turesky Modified Quigley Hein Plaque Index) and gingival index scores >1.0 (Loe and Silness gingival index) in good general health and who met other study criteria were enrolled in the clinical study. Subjects were evaluated for plaque and gingival index scores and were randomly assigned to perform twice‐daily oral hygiene with either the test or the control toothpaste for the next 6 months. One hundred and fifty (150) subjects [test toothpaste (n = 72) and control toothpaste (n = 78)] completed the 6‐month clinical study with evaluable data. Post‐treatment assessments identical to baseline were conducted after 3‐month and 6‐month use of an assigned product after subjects refrained from oral hygiene for 12 h prior to each evaluation. Comparisons of the treatment groups with respect to baseline‐adjusted gingival, plaque, and bleeding index scores at the follow‐up examinations were performed using analyses of covariance (ANCOVA). All statistical tests of hypotheses were two‐sided and employed a level of significance of p < 0.05.ResultsNo significant intergroup differences were noted between treatment groups for age and gender by two‐sample t‐test and chi‐square analyses, respectively (p > 0.05). Furthermore, the treatment groups demonstrated no differences at baseline for plaque, gingival and bleeding index scores by a two‐sample t‐test (p > 0.05). At 3‐month and 6‐month examination, the test toothpaste exhibited progressive reductions in plaque, gingival and bleeding scores as compared to control toothpaste as showed by ANCOVA (p < 0.001). In comparison with the control, the test demonstrated reductions in 23.5%, 25.6%, and 73.3% for dental plaque, gingival index and bleeding index outcomes, respectively, at the final visit. Reductions in the frequencies of sites with higher clinical scores were noted over the study with more sites registering improvements in the test group than in the control group.ConclusionsRoutine oral hygiene with the test toothpaste formulated with herbal ingredients and zinc demonstrated a clinical adjunctive improvement in oral hygiene and parameters of gingival health as compared to brushing with a fluoride toothpaste.
Identification of new Anopheles gambiae transcriptional enhancers using a cross‐species prediction approach
Authors: Schember I. , Halfon M. S. 
Published: April 2021

AbstractThe success of transgenic mosquito vector control approaches relies on well‐targeted gene expression, requiring the identification and characterization of a diverse set of mosquito promoters and transcriptional enhancers. However, few enhancers have been characterized in Anopheles gambiae to date. Here, we employ the SCRMshaw method we previously developed to predict enhancers in the A. gambiae genome, preferentially targeting vector‐relevant tissues such as the salivary glands, midgut and nervous system. We demonstrate a high overall success rate, with at least 8 of 11 (73%) tested sequences validating as enhancers in an in vivo xenotransgenic assay. Four tested sequences drive expression in either the salivary gland or the midgut, making them directly useful for probing the biology of these infection‐relevant tissues. The success of our study suggests that computational enhancer prediction should serve as an effective means for identifying A. gambiae enhancers with activity in tissues involved in malaria propagation and transmission.
Metabolic dysfunction induced by a high‐fat diet modulates hematopoietic stem and myeloid progenitor cells in brown adipose tissue of mice
Authors: Mincham Kyle T , Panchal Kunjal , Hart Prue H , Lucas Robyn M , Feelisch Martin , Weller Richard B , Matthews Vance B , Strickland Deborah H , Gorman Shelley 
Published: April 2021

AbstractBrown adipose tissue (BAT) may be an important metabolic regulator of whole‐body glucose. While important roles have been ascribed to macrophages in regulating metabolic functions in BAT, little is known of the roles of other immune cells subsets, particularly dendritic cells (DCs). Eating a high‐fat diet may compromise the development of hematopoietic stem and progenitor cells (HSPCs)—which give rise to DCs—in bone marrow, with less known of its effects in BAT. We have previously demonstrated that ongoing exposure to low‐dose ultraviolet radiation (UVR) significantly reduced the ‘whitening’ effect of eating a high‐fat diet upon interscapular (i) BAT of mice. Here, we examined whether this observation may be linked to changes in the phenotype of HSPCs and myeloid‐derived immune cells in iBAT and bone marrow of mice using 12‐colour flow cytometry. Many HSPC subsets declined in both iBAT and bone marrow with increasing metabolic dysfunction. Conversely, with rising adiposity and metabolic dysfunction, conventional DCs (cDCs) increased in both of these tissues. When compared with a low‐fat diet, consumption of a high‐fat diet significantly reduced proportions of myeloid, common myeloid and megakaryocyte–erythrocyte progenitors in iBAT, and short‐term hematopoietic stem cells in bone marrow. In mice fed the high‐fat diet, exposure to low‐dose UVR significantly reduced proportions of cDCs in iBAT, independently of nitric oxide release from irradiated skin [blocked using the scavenger 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl‐3‐oxide potassium salt (cPTIO)], but did not significantly modify HSPC subsets in either tissue. Further studies are needed to determine whether changes in these cell populations contribute towards metabolic dysfunction.
Intranasal immunization with Ag85B peptide 25 displayed on Lactococcuslactis using the PilVax platform induces antigen‐specific B‐ and T‐cell responses
Authors: Blanchett Samuel , Tsai Catherine JY , Sandford Sarah , Loh Jacelyn MS , Huang Lucy , Kirman Joanna R , Proft Thomas 
Published: April 2021

AbstractMycobacterium tuberculosis (Mtb) remains a global epidemic despite the widespread use of Bacillus Calmette–Guérin (BCG). Consequently, novel vaccines are required to facilitate a reduction in Mtb morbidity and mortality. PilVax is a peptide delivery strategy for the generation of highly specific mucosal immune responses and is based on the food‐grade bacterium Lactococcus lactis that is used to express selected peptides engineered within the Streptococcus pyogenes M1T1 pilus, allowing for peptide amplification, stabilization and enhanced immunogenicity. In the present study, the dominant T‐cell epitope from the Mtb protein Ag85B was genetically engineered into the pilus backbone subunit and expressed on the surface of L. lactis. Western blot and flow cytometry confirmed formation of pilus containing the peptide DNA sequence. B‐cell responses in intranasally vaccinated mice were analyzed by ELISA while T‐cell responses were analyzed by flow cytometry. Serum titers of peptide‐specific immunoglobulin (Ig) G and IgA were detected, confirming that vaccination produced antibodies against the cognate peptide. Peptide‐specific IgA was also detected across several mucosal sites sampled. Peptide‐specific CD4+ T cells were detected at levels similar to those of mice immunized with BCG. PilVax immunization resulted in an unexpected increase in the numbers of CD3+CD4–CD8– [double negative (DN)] T cells in the lungs of vaccinated mice. Analysis of cytokine production following stimulation with the cognate peptide showed the major cytokine producing cells to be CD4+ T cells and DN T cells. This study provides insight into the antibody and peptide‐specific cellular immune responses generated by PilVax vaccination and demonstrates the suitability of this vaccine for conducting a protection study.
Imposing water deficit on modern and wild wheat collections to identify drought‐resilient genotypes
Authors: Morsy Sabah M. , Elbasyoni Ibrahim S. , Abdallah Ahmed M. , Baenziger Petter Stephen 
Published: April 2021

AbstractBreeding for drought tolerance is the most effective approach to mitigate drought effects. The prime goal of the current study was to identify potentially drought‐tolerant wheat (Triticum aestivum L.) genotypes. Therefore, an extensive collection of wheat genotypes (2,100) was evaluated under two water regimes, that is water deficit (WD, 50% ETc ‘crop Evapotranspiration’) and well‐watered (WW, 100% of ETc) across several environments in Egypt. The number of days to flowering (NDF), plant height (PH) and grain yield (GY) were recorded under both water regimes across environments. Additionally, three yield‐based drought indices and water‐use efficiency (WUE) were calculated for the top 30% yielding genotypes (that produced economical GY; 3.58 ton ha−1 for WD and 7.5 ton ha−1 for WW). The results indicated a significant effect for environments, water stress, and genotypes, as well as the second‐ and third‐order interactions across all traits. WD significantly reduced PH, NDF, and GY by 5.0 cm, 10.6 days and 50.0%, respectively. PH, NDF and GY were highly correlated. However, the direction and magnitude of correlation under normal conditions were different from those under WD. For example, under WW conditions, late flowering and taller genotypes tended to produce higher GY. In contrast, under WD, earlier and shorter wheat genotypes tended to produce higher GY. According to the drought tolerance index (DTI), 254 genotypes were considered drought tolerance (DTI > 1). Based on WUE, DTI and GY under WD, 80 genotypes outperformed the commercially grown Egyptian cultivars. Our results implied that the evaluated collection might be a valuable source not only for drought‐tolerant genotypes but also for highly yielding water‐efficient genotypes under favourable conditions in Egypt and similar geographic regions.