bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic diversity in micro-endemic plants from highland grasslands in southern Brazil
Authors: Souza Analu , Giudicelli Giovanna C , Teixeira Marcelo C , Turchetto Caroline , Bonatto Sandro L , Freitas Loreta B 
Published: September 2021

AbstractPopulation genetic structure results from the interaction between historical events, current ecological conditions and life traits. The genetic structure and gene flow between populations are important to species dynamics, mainly for rare and endangered species that are more vulnerable to landscape changes and fragmentation. Here we evaluated the genetic diversity, population structure and gene exchange in Petunia bonjardinensis, P. reitzii and P. saxicola, three rare species endemic to subtropical highland grasslands in southern South America. We analysed the genetic diversity and structure considering historical events, such as founder effect and climate changes, and biological traits of each species. We also estimated the conservation status for these three species. We collected samples from all adult individuals and occurrence sites that could be found at the same flowering season and genotyped them for 13 nuclear microsatellite markers. Our results indicate that rarity is probably historical for these species, given that we found no genetic evidence for recent bottlenecks. Petunia bonjardinensis, with the largest occurrence area and population sizes, displayed the higher diversity indices. The other two showed lower genetic diversity and are geographically most restricted. Gene exchange among these species was low, although they share some ancestral genetic polymorphism. Historical migration, founder effects and Pleistocene climate cycles ae the main factors explaining genetic diversity, and this was also influenced by reproductive biology and recent habitat loss, whereas the landscape influences the structure. Based on IUCN criteria, the three species are endangered, and the main risk for their survival is probably anthropic activity in the occurrence area. We recommend an urgent programme for the preservation of these species in situ and ex situ.
Crosstalk between gut microbiota and sepsis
Authors: Niu Mengwei , Chen Peng 
Published: September 2021

Abstract
Sepsis is an overwhelming inflammatory response to microbial infection. Sepsis management remains a clinical challenge. The role of the gut microbiome in sepsis has gained some attention. Recent evidence has demonstrated that gut microbiota regulate host physiological homeostasis mediators, including the immune system, gut barrier function and disease susceptibility pathways. Therefore, maintenance or restoration of microbiota and metabolite composition might be a therapeutic or prophylactic target against critical illness. Fecal microbiota transplantation and supplementation of probiotics are microbiota-based treatment methods that are somewhat limited in terms of evidence-based efficacy. This review focuses on the importance of the crosstalk between the gastrointestinal ecosystem and sepsis to highlight novel microbiota-targeted therapies to improve the outcomes of sepsis treatment.
Mentorship and Relationality
Authors: Bordeaux Clementine 
Published: September 2021

Abstract
To be a good relative, as defined by Dakota scholar Ella Cara Deloria (1889–1971), means to follow cultural protocols of kinship in the shaping of relationships. In this article, the author utilizes Deloria’s employment of “being a good relative” within a Lakota/Dakota understanding and Indigenous studies’ articulations of relationality to discuss mentorship. Utilizing the Indigenous studies’ methodology of self-reflexivity, the author provides an analysis of mentorship experiences within different university settings.
Cortical Serotonergic and Catecholaminergic Denervation in MPTP-Treated Parkinsonian Monkeys
Authors: Masilamoni Gunasingh Jeyaraj , Weinkle Allison , Papa Stella M , Smith Yoland 
Published: September 2021

Abstract
Decreased cortical serotonergic and catecholaminergic innervation of the frontal cortex has been reported at early stages of Parkinson’s disease (PD). However, the limited availability of animal models that exhibit these pathological features has hampered our understanding of the functional significance of these changes during the course of the disease. In the present study, we assessed longitudinal changes in cortical serotonin and catecholamine innervation in motor-symptomatic and asymptomatic monkeys chronically treated with low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Densitometry and unbiased stereological techniques were used to quantify changes in serotonin and tyrosine hydroxylase (TH) immunoreactivity in frontal cortices of 3 control monkeys and 3 groups of MPTP-treated monkeys (motor-asymptomatic [N = 2], mild parkinsonian [N = 3], and moderate parkinsonian [N = 3]). Our findings revealed a significant decrease (P &lt; 0.001) in serotonin innervation of motor (Areas 4 and 6), dorsolateral prefrontal (Areas 9 and 46), and limbic (Areas 24 and 25) cortical areas in motor-asymptomatic MPTP-treated monkeys. Both groups of symptomatic MPTP-treated animals displayed further serotonin denervation in these cortical regions (P &lt; 0.0001). A significant loss of serotonin-positive dorsal raphe neurons was found in the moderate parkinsonian group. On the other hand, the intensity of cortical TH immunostaining was not significantly affected in motor asymptomatic MPTP-treated monkeys, but underwent a significant reduction in the moderate symptomatic group (P &lt; 0.05). Our results indicate that chronic intoxication with MPTP induces early pathology in the corticopetal serotonergic system, which may contribute to early non-motor symptoms in PD.
Verbal and General IQ Associate with Supragranular Layer Thickness and Cell Properties of the Left Temporal Cortex
Authors: Heyer D B , Wilbers R , Galakhova A A , Hartsema E , Braak S , Hunt S , Verhoog M B , Muijtjens M L , Mertens E J , Idema S , Baayen J C , de Witt Hamer P , Klein M , McGraw M , Lein E S , de Kock C P J , Mansvelder H D , Goriounova N A 
Published: September 2021

Abstract
The left temporal lobe is an integral part of the language system and its cortical structure and function associate with general intelligence. However, whether cortical laminar architecture and cellular properties of this brain area relate to verbal intelligence is unknown. Here, we addressed this using histological analysis and cellular recordings of neurosurgically resected temporal cortex in combination with presurgical IQ scores. We find that subjects with higher general and verbal IQ scores have thicker left (but not right) temporal cortex (Brodmann area 21, BA21). The increased thickness is due to the selective increase in layers 2 and 3 thickness, accompanied by lower neuron densities, and larger dendrites and cell body size of pyramidal neurons in these layers. Furthermore, these neurons sustain faster action potential kinetics, which improves information processing. Our results indicate that verbal mental ability associates with selective adaptations of supragranular layers and their cellular micro-architecture and function in left, but not right temporal cortex.
Top-Down Modulation of Early Visual Processing in V1: Dissociable Neurophysiological Effects of Spatial Attention, Attentional Load and Task-Relevance
Authors: Wolf Maren-Isabel , Bruchmann Maximilian , Pourtois Gilles , Schindler Sebastian , Straube Thomas 
Published: September 2021

Abstract
Until today, there is an ongoing discussion if attention processes interact with the information processing stream already at the level of the C1, the earliest visual electrophysiological response of the cortex. We used two highly powered experiments (each N = 52) and examined the effects of task relevance, spatial attention, and attentional load on individual C1 amplitudes for the upper or lower visual hemifield. Bayesian models revealed evidence for the absence of load effects but substantial modulations by task-relevance and spatial attention. When the C1-eliciting stimulus was a task-irrelevant, interfering distracter, we observed increased C1 amplitudes for spatially unattended stimuli. For spatially attended stimuli, different effects of task-relevance for the two experiments were found. Follow-up exploratory single-trial analyses revealed that subtle but systematic deviations from the eye-gaze position at stimulus onset between conditions substantially influenced the effects of attention and task relevance on C1 amplitudes, especially for the upper visual field. For the subsequent P1 component, attentional modulations were clearly expressed and remained unaffected by these deviations. Collectively, these results suggest that spatial attention, unlike load or task relevance, can exert dissociable top-down modulatory effects at the C1 and P1 levels.
Brain Responses to Surprising Stimulus Offsets: Phenomenology and Functional Significance
Authors: Somervail R , Bufacchi R J , Salvatori C , Neary-Zajiczek L , Guo Y , Novembre G , Iannetti G D 
Published: September 2021

Abstract
Abrupt increases of sensory input (onsets) likely reflect the occurrence of novel events or objects in the environment, potentially requiring immediate behavioral responses. Accordingly, onsets elicit a transient and widespread modulation of ongoing electrocortical activity: the Vertex Potential (VP), which is likely related to the optimisation of rapid behavioral responses. In contrast, the functional significance of the brain response elicited by abrupt decreases of sensory input (offsets) is more elusive, and a detailed comparison of onset and offset VPs is lacking. In four experiments conducted on 44 humans, we observed that onset and offset VPs share several phenomenological and functional properties: they (1) have highly similar scalp topographies across time, (2) are both largely comprised of supramodal neural activity, (3) are both highly sensitive to surprise and (4) co-occur with similar modulations of ongoing motor output. These results demonstrate that the onset and offset VPs largely reflect the activity of a common supramodal brain network, likely consequent to the activation of the extralemniscal sensory system which runs in parallel with core sensory pathways. The transient activation of this system has clear implications in optimizing the behavioral responses to surprising environmental changes.
Reorganization of the Neurobiology of Language After Sentence Overlearning
Authors: Skipper Jeremy I , Aliko Sarah , Brown Stephen , Jo Yoon Ju , Lo Serena , Molimpakis Emilia , Lametti Daniel R 
Published: September 2021

Abstract
It is assumed that there are a static set of “language regions” in the brain. Yet, language comprehension engages regions well beyond these, and patients regularly produce familiar “formulaic” expressions when language regions are severely damaged. These suggest that the neurobiology of language is not fixed but varies with experiences, like the extent of word sequence learning. We hypothesized that perceiving overlearned sentences is supported by speech production and not putative language regions. Participants underwent 2 sessions of behavioral testing and functional magnetic resonance imaging (fMRI). During the intervening 15 days, they repeated 2 sentences 30 times each, twice a day. In both fMRI sessions, they “passively” listened to those sentences, novel sentences, and produced sentences. Behaviorally, evidence for overlearning included a 2.1-s decrease in reaction times to predict the final word in overlearned sentences. This corresponded to the recruitment of sensorimotor regions involved in sentence production, inactivation of temporal and inferior frontal regions involved in novel sentence listening, and a 45% change in global network organization. Thus, there was a profound whole-brain reorganization following sentence overlearning, out of “language” and into sensorimotor regions. The latter are generally preserved in aphasia and Alzheimer’s disease, perhaps explaining residual abilities with formulaic expressions in both.
Aberrant Subnetwork and Hub Dysconnectivity in Adult Bipolar Disorder: A Multicenter Graph Theory Analysis
Authors: Nabulsi Leila , McPhilemy Genevieve , O’Donoghue Stefani , Cannon Dara M , Kilmartin Liam , O’Hora Denis , Sarrazin Samuel , Poupon Cyril , D’Albis Marc-Antoine , Versace Amelia , Delavest Marine , Linke Julia , Wessa Michèle , Phillips Mary L , Houenou Josselin , McDonald Colm 
Published: September 2021

AbstractNeuroimaging evidence implicates structural network-level abnormalities in bipolar disorder (BD); however, there remain conflicting results in the current literature hampered by sample size limitations and clinical heterogeneity. Here, we set out to perform a multisite graph theory analysis to assess the extent of neuroanatomical dysconnectivity in a large representative study of individuals with BD.This cross-sectional multicenter international study assessed structural and diffusion-weighted magnetic resonance imaging data obtained from 109 subjects with BD type 1 and 103 psychiatrically healthy volunteers.Whole-brain metrics, permutation-based statistics, and connectivity of highly connected nodes were used to compare network-level connectivity patterns in individuals with BD compared with controls.The BD group displayed longer characteristic path length, a weakly connected left frontotemporal network, and increased rich-club dysconnectivity compared with healthy controls.Our multisite findings implicate emotion and reward networks dysconnectivity in bipolar illness and may guide larger scale global efforts in understanding how human brain architecture impacts mood regulation in BD.
Neonatal Hypoxia-Ischemia Causes Persistent Intracortical Circuit Changes in Layer 4 of Rat Auditory Cortex
Authors: Sheikh Aminah , Meng Xiangying , Kao Joseph P Y , Kanold Patrick O 
Published: September 2021

Abstract
The connection between early brain injury and subsequent development of disorders is unknown. Neonatal hypoxia-ischemia (HI) alters circuits associated with subplate neurons (SPNs). SPNs are among the first maturing cortical neurons, project to thalamorecipient layer 4 (L4), and are required for the development of thalamocortical connections. Thus, early HI might influence L4 and such influence might persist. We investigated functional circuits to L4 neurons in neonatal rat HI models of different severities (mild and moderate) shortly after injury and at adolescence. We used laser-scanning photostimulation in slices of auditory cortex during P5–10 and P18–23. Mild injuries did not initially (P6/P7) alter the convergence of excitatory inputs from L2/3, but hyperconnectivity emerged by P8–10. Inputs from L4 showed initial hypoconnectivity which resolved by P8–10. Moderate injuries resulted in initial hypoconnectivity from both layers which resolved by P8–10 and led to persistent strengthening of connections. Inhibitory inputs to L4 cells showed similar changes. Functional changes were mirrored by reduced dendritic complexity. We also observed a persistent increase in similarity of L4 circuits, suggesting that HI interferes with developmental circuit refinement and diversification. Altogether, our results show that neonatal HI injuries lead to persistent changes in intracortical connections.
A review of the flavor profile of metal salts: understanding the complexity of metallic sensation
Authors: Ecarma Michelle J Y , Nolden Alissa A 
Published: September 2021

Abstract
The oral sensation of metallic is a complex experience. Much of our current understanding of metallic sensation is from the investigation of metal salts, which elicit diverse sensations, including taste, smell, and chemesthetic sensations, and therefore meet the definition of a flavor rather than a taste. Due to the involvement of multiple chemosensory systems, it can be challenging to define and characterize metallic sensation. Here, we provide a comprehensive review of the psychophysical studies quantifying and characterizing metallic sensation, focusing on metal salts. We examine the factors that impact perception, including anion complex, concentration, nasal occlusion, and pH. In addition, we summarize the receptors thought to be involved in the perception of metallic sensation (i.e., TRPV1, T1R3, TRPA1, and T2R7) either as a result of in vitro assays or from studies in knock-out mice. By enhancing our scientific understanding of metallic sensation and its transduction pathways, it has the potential to improve food and pharmaceuticals, help identify suppression or masking strategies, and improve the ability to characterize individual differences in metallic sensation. It also has the potential to translate to clinical populations by addressing the disparities in knowledge and treatment options for individuals suffering from metallic taste disorder (i.e., phantom taste or “metal mouth”). Future psychophysical studies investigating the sensory perception of metal salts should include a range of compounds and diverse food matrices, coupled with modern sensory methods, which will help to provide a more comprehensive understanding of metallic sensation.
Determination of Voriconazole in Human Plasma Using RP-HPLC/UV-VIS Detection: Method Development and Validation; Subsequently Evaluation of Voriconazole Pharmacokinetic Profile in Pakistani Healthy Male Volunteers
Authors: Mushtaq Mehwish , Shah Yasar , Samiullah   , Nasir Fazli , Khan Haroon , Faheem Muhammad , Nadeem Atif , Khan Sundas , Khan Sumaira Irum , Abbas Muhammad , Khuda Fazli , Iftikhar Tayyaba 
Published: September 2021

Abstract
In this research work, an isocratic, reversed-phase high-performance liquid chromatography-ultraviolet/visible detector method was developed for analysis of voriconazole standard (stock-solution) and in plasma samples. Optimization and validation of the method was carried out as per international guidelines. The method offered a simple liquid–liquid extraction technique, which exhibited best recovery of voriconazole along with fluconazole, i.e., internal standard. Different experimental conditions were tried and ultimately, the best outcomes were accomplished utilizing C-18 Perkin-Elmer® column with particulars of 150 mm length, 4.6 mm inner diameter and 5 μm particle size, protected by an RP-18 Perkin-Elmer® Pre-column guard cartridge with specifications of 10 μm particle size, 30 mm length and 4.6 mm inner diameter, utilizing mobile-phase of acetonitrile-water (ACN: H2O) in proportion of 60: 40 v/v, having a flow rate of 1.5 mL/min, and wavelength of 254 nm. All the analytes were observed to be separated in ≤7 min. A linear calibration curve was obtained at concentration range of 01–10 μg/mL of voriconazole. The correlation coefficient of voriconazole was observed to be 0.999, and average recovery (in percent) was 97.4%, whereas the relative standard deviation value was ≤2%. The lower limit of detection was 0.01 μg/mL, whereas, lower limit of quantification was 0.03 μg/mL, respectively. This developed method provided outstanding results of all validation parameters, i.e., recovery, accuracy, selectivity, precision and reproducibility. The method proposed for voriconazole analysis was applied effectively for further research investigation of voriconazole in human-plasma samples (to assess the pharmacokinetic parameters), pharmaceutical formulations and pharmacokinetic drug–drug interaction’s.
A New, Rapid and Simple RP-HPLC Method for Stability Quantification of a Protease Inhibitor in Tablets
Authors: Rossi Rochele Cassanta , Moura Josué Guilherme Lisbôa , Mossmann Vanessa , Weimer Patrícia , Fröehlich Pedro Eduardo 
Published: September 2021

Abstract
Fosamprenavir calcium is a protease inhibitor widely used in the treatment and prevention of human immunodeficiency virus and acquired immunodeficiency syndrome. This protease inhibitor serves as a prodrug of amprenavir, offering better oral bioavailability. Although this drug was approved by the FDA in 2003, there are few methods established for quantifying the stability for quality control analysis of fosamprenavir-coated tablets. The purpose of the study was to develop and validate a method for determining the stability of fosamprenavir-coated tablets (Telzir®) that may be applied by any quality control laboratory. Chromatographic separation was performed using a Vertical RP-18 column programmed to run a gradient elution with sodium acetate buffer and acetonitrile. Flow rate was 1.2 mL min−1 for a total run time of 15 min. Ultraviolet detection was set at 264 nm and the use of a photodiode array detector in scan mode allowed selectivity confirmation by peak purity evaluation. The analyte peak was found to be adequately separated from degradation products generated during forced degradation studies. Thus, the proposed method was found to accurately indicate stability and was sufficient for routine quantitative analysis of fosamprenavir in coated tablets without interference from major degradation products and excipients.
Two Validated Chromatographic Methods for Determination of Ciprofloxacin HCl, One of its Specified Impurities and Fluocinolone Acetonide in Newly Approved Otic Solution
Authors: Tantawy Mahmoud A , Wahba Israa A , Saad Samah S , Ramadan Nesrin K 
Published: September 2021

Abstract
Two sensitive, selective and precise chromatographic methods have been established for concomitant quantification of ciprofloxacin HCl (CIP), fluocinolone acetonide (FLU) along with ciprofloxacin impurity A (CIP-imp A). The first method was thin-layer chromatography (TLC-densitometry) where separation was accomplished using TLC silica plates 60 G.F254 as a stationary phase and chloroform–methanol–33%ammonia (4.6:4.4:1, by volume) as a developing system. The obtained plates were scanned at 260 nm over concentration ranges of 1.0–40.0, 0.6–20.0 and 1.0–40.0 μg band−1 for CIP, FLU and CIP-imp A, respectively. The second method was based on high-performance liquid chromatography using a Zorbax ODS column (5 μm, 150 × 4.6 mm i.d.) where adequate separation was achieved through a mobile phase composed of phosphate buffer pH 3.6–acetonitrile (45:55, v/v) at flow rate 1.0 mL min−1 with ultraviolet detection at 254 nm. Linear regressions were obtained in the range of 1.0–40.0 μg mL−1 for CIP, 0.6–20.0 μg mL−1 for FLU and 1.0–40.0 μg mL−1 for CIP-imp A. The suggested methods were validated in compliance with the International Conference on Harmonization guidelines and were successfully applied for determination of CIP and FLU in bulk powder and newly marketed otic solution.
Development and Validation of a Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) Method for Identification, Assay and Estimation of Related Substances of Ivermectin in Bulk Drug Batches of Ivermectin Drug Substance
Authors: Zhao Daoli , Wimalasinghe Rasangi M , Wang Lin , Rustum Abu M 
Published: September 2021

Abstract
A reversed-phase high-performance liquid chromatography (RP-HPLC) method has been developed and validated for the identification and assay of Ivermectin, including the identification and estimation of its process-related impurities and degradation products in bulk drug substance of Ivermectin. Analytes were separated on a HALO C18 column (100 mm × 4.6 mm I.D., 2.7 μm particle size) maintained at 40 °C (column temperature) with gradient elution. All analytes of interests were adequately separated within 25 min. All degradation products, process-related impurities and assay were monitored by ultraviolet detection at 254 nm. The new HPLC method described here successfully separated an isomer peak of the active pharmaceutical ingredient (API) from the major API peak. This newly separated isomer peak is around 1.2 to 1.5% (peak area) in typical API samples, and coelutes with the major API peak by all current HPLC methods. Quantitation limit of the HPLC method is 0.1% of target analytical concentration (~1.0 μg/mL). This method has been demonstrated to be accurate, robust, significantly higher degree of selectivity compared to the HPLC methods of Ivermectin drug substance reported in the literature and in the compendial HPLC methods prescribed in the current USA and European Pharmacopeia.