bluuebunny/crossref_metadata_2025_split huggingface dataset:
Within-Host Microevolution of Pseudomonas aeruginosa Urinary Isolates: A Seven-Patient Longitudinal Genomic and Phenotypic Study
Authors: Cottalorda Agnès , Leoz Marie , Dahyot Sandrine , Gravey François , Grand Maxime , Froidure Thomas , Aujoulat Fabien , Le Hello Simon , Jumas-Bilak Estelle , Pestel-Caron Martine 
Published: January 2021

BackgroundPseudomonas aeruginosa is responsible for up to 10% of healthcare associated urinary tract infections (UTI), which can be difficult to treat and can lead to bacterial persistence. While numerous whole genome sequencing (WGS) analyses have explored within-host genomic adaptation and microevolution of P. aeruginosa during cystic fibrosis (CF) infections, little is known about P. aeruginosa adaptation to the urinary tract.ResultsWhole genome sequencing was performed on 108 P. aeruginosa urinary isolates, representing up to five isolates collected from 2 to 5 successive urine samples from seven patients hospitalized in a French hospital over 48–488 days. Clone type single nucleotide polymorphisms (ctSNPs) analysis revealed that each patient was colonized by a single clone type (&lt;6000 SNPs between two isolates) at a given time and over time. However, 0–126 SNPs/genome/year were detected over time. Furthermore, large genomic deletions (1–5% of the genome) were identified in late isolates from three patients. For 2 of them, a convergent deletion of 70 genes was observed. Genomic adaptation (SNPs and deletion) occurred preferentially in genes encoding transcriptional regulators, two-component systems, and carbon compound catabolism. This genomic adaptation was significantly associated with a reduced fitness, particularly in artificial urine medium, but no strict correlation was identified between genomic adaptation and biofilm formation.ConclusionThis study provides the first insight into P. aeruginosa within-host evolution in the urinary tract. It was driven by mutational mechanisms and genomic deletions and could lead to phenotypic changes in terms of fitness and biofilm production. Further metabolomic and phenotypic analyses are needed to describe in-depth genotype-phenotype associations in this complex and dynamic host-environment.
NeuroExercise: The Effect of a 12-Month Exercise Intervention on Cognition in Mild Cognitive Impairment—A Multicenter Randomized Controlled Trial
Authors: Stuckenschneider Tim , Sanders Marit L. , Devenney Kate E. , Aaronson Justine A. , Abeln Vera , Claassen Jurgen A. H. R. , Guinan Emer , Lawlor Brian , Meeusen Romain , Montag Christian , Olde Rikkert Marcel G. M. , Polidori M. Cristina , Reuter Martin , Schulz Ralf-Joachim , Vogt Tobias , Weber Bernd , Kessels Roy P. C. , Schneider Stefan 
Published: January 2021

Exercise intervention studies in mild cognitive impairment (MCI), a prodromal stage of Alzheimer's disease (AD), have demonstrated inconsistent yet promising results. Addressing the limitations of previous studies, this trial investigated the effects of a 12-month structured exercise program on the progression of MCI. The NeuroExercise study is a multicenter randomized controlled trial across three European countries (Ireland, Netherlands, Germany). Hundred and eighty-three individuals with amnestic MCI were included and were randomized to a 12-month exercise intervention (3 units of 45 min) of either aerobic exercise (AE; n = 60), stretching and toning exercise (ST; n = 65) or to a non-exercise control group (CG; n = 58). The primary outcome, cognitive performance, was determined by an extensive neuropsychological test battery. For the primary complete case (CC) analyses, between-group differences were analyzed with analysis of covariance under two conditions: (1) the exercise group (EG = combined AE and ST groups) compared to the CG and (2) AE compared to ST. Primary analysis of the full cohort (n = 166, 71.5 years; 51.8% females) revealed no between-group differences in composite cognitive score [mean difference (95% CI)], 0.12 [(−0.03, 0.27), p = 0.13] or in any cognitive domain or quality of life. VO2 peak was significantly higher in the EG compared to the CG after 12 months [−1.76 (−3.39, −0.10), p = 0.04]. Comparing the two intervention groups revealed a higher VO2peak level in the aerobic exercise compared to the stretching and toning group, but no differences for the other outcomes. A 12-month exercise intervention did not change cognitive performance in individuals with amnestic MCI in comparison to a non-exercise CG. An intervention effect on physical fitness was found, which may be an important moderator for long term disease progression and warrants long-term follow-up investigations.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT02913053, identifier: NCT02913053.
Effects of Continuous Epidural Injection of Dexamethasone on Blood Glucose, Blood Lipids, Plasma Cortisol and ACTH in Patients With Neuropathic Pain
Authors: Liu Xiao-hui , Du Yu-min , Cong Hai-jing , Liu Guang-zhao , Ren Yu-E 
Published: January 2021

Objective:To study the effects of continuous epidural injection of dexamethasone on blood glucose, blood lipids, plasma cortisol, and adrenocorticotropic hormone (ACTH) in patients with neuropathic pain.Methods:Thirty patients with cervical spondylotic radiculopathy, lumbar disc herniation, herpes pain or postherpetic neuralgia were randomly divided into three groups and were treated with different doses of epidural injection of dexamethasone (Group S with a concentration of 25 μg/mL; Group M with a concentration of 50 μg/mL; Group L with a concentration of 100 μg/mL). Epidural catheterization placement was guided by computed tomography (CT), and was connected to the analgesic pump for 10 days. Visual Analog Score (VAS), fasting blood glucose (FBG), total cholesterol (CHOL), triglyceride (TG), 2 h postprandial blood glucose (2hPG) and the concentrations of cortisol, ACTH were measured before injection (T0), 2, 4, 6, 8, and 10 days during injection (D2, D4, D6, D8, D10), and 7, 14, 21, 28 days (W1, W2, W3, W4) after injection.Results:During and after the treatment, VAS score was significantly decreased, and group M and L had the lowest VAS score. The concentrations of cortisol and ACTH were significantly lower during the treatment, but all of them recovered to the normal level after stopping the injection. The treatment did not affect the CHOL and TG concentrations.Discussion:Epidural injection of dexamethasone at the concentration of 50 μg/mL is recommended for patients with neuropathic pain because of its good analgesic effect and less adverse effect on blood glucose, plasma cortisol, and ACTH.
Quantitative Evaluation of 18F-Flutemetamol PET in Patients With Cognitive Impairment and Suspected Alzheimer's Disease: A Multicenter Study
Authors: Matsuda Hiroshi , Ito Kengo , Ishii Kazunari , Shimosegawa Eku , Okazawa Hidehiko , Mishina Masahiro , Mizumura Sunao , Ishii Kenji , Okita Kyoji , Shigemoto Yoko , Kato Takashi , Takenaka Akinori , Kaida Hayato , Hanaoka Kohei , Matsunaga Keiko , Hatazawa Jun , Ikawa Masamichi , Tsujikawa Tetsuya , Morooka Miyako , Ishibashi Kenji , Kameyama Masashi , Yamao Tensho , Miwa Kenta , Ogawa Masayo , Sato Noriko 
Published: January 2021

Background: In clinical practice, equivocal findings are inevitable in visual interpretation of whether amyloid positron emission tomography (PET) is positive or negative. It is therefore necessary to establish a more objective quantitative evaluation method for determining the indication for disease-modifying drugs currently under development.Aims: We aimed to determine cutoffs for positivity in quantitative analysis of 18F-flutemetamol PET in patients with cognitive impairment and suspected Alzheimer's disease (AD). We also evaluated the clinical efficacy of amyloid PET in the diagnosis of AD. This study was registered in the Japan Registry of Clinical Trials (jRCTs, 031180321).Methods: Ninety-three patients suspected of having AD underwent 18F-flutemetamol PET in seven institutions. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by two board-certified nuclear medicine physicians. If the two readers obtained different interpretations, the visual rating was rerun until they reached consensus. The PET images were quantitatively analyzed using the standardized uptake value ratio (SUVR) and standardized Centiloid (CL) scale with the whole cerebellum as a reference area.Results: Visual interpretation obtained 61 positive and 32 negative PET scans. Receiver operating characteristic analysis determined the best agreement of quantitative assessments and visual interpretation of PET scans to have an area under curve of 0.982 at an SUVR of 1.13 and a CL of 16. Using these cutoff values, there was high agreement between the two approaches (kappa = 0.88). Five discordant cases had SUVR and CL values ranging from 1.00 to 1.22 and from 1 to 26, respectively. In these discordant cases, either diffuse or mildly focal elevation of cortical activity confused visual interpretation. The amyloid PET outcome significantly altered the diagnosis of AD (χ2 = 51.3, p &lt; 0.0001). PET imaging elevated the proportions of the very high likelihood category from 20.4 to 46.2% and the very low likelihood category from 0 to 22.6%.Conclusion: Quantitative analysis of amyloid PET using 18F-flutemetamol can objectively evaluate amyloid positivity using the determined cutoffs for SUVR and CL. Moreover, amyloid PET may have added value over the standard diagnostic workup in dementia patients with cognitive impairment and suspected AD.
Early-Onset Parkinson Disease Screening in Patients From Nigeria
Authors: Milanowski Lukasz M. , Oshinaike Olajumoke , Broadway Benjamin J. , Lindemann Jennifer A. , Soto-Beasley Alexandra I. , Walton Ronald L. , Hanna Al-Shaikh Rana , Strongosky Audrey J. , Fiesel Fabienne C. , Ross Owen A. , Springer Wolfdieter , Ogun Shamsideen Abayomi , Wszolek Zbigniew K. 
Published: January 2021

Introduction: Nigeria is one of the most populated countries in the world; however, there is a scarcity of studies in patients with age-related neurodegenerative diseases, such as Parkinson disease (PD). The aim of this study was to screen patients with PD including a small cohort of early-onset PD (EOPD) cases from Nigeria for PRKN, PINK1, DJ1, SNCA multiplication, and LRRK2 p.G2019S.Methods: We assembled a cohort of 109 Nigerian patients with PD from the four main Nigerian tribes: Yoruba, Igbo, Edo, and Hausa. Fifteen cases [14 from the Yoruba tribe (93.3%)] had EOPD (defined as age-at-onset &lt;50 years). All patients with EOPD were sequenced for the coding regions of PRKN, PINK1, and DJ1. Exon dosage analysis was performed with a multiplex ligation-dependent probe amplification assay, which also included a SNCA probe and LRRK2 p.G2019S. We screened for LRRK2 p.G2019S in the entire PD cohort using a genotyping assay. The PINK1 p.R501Q functional analysis was conducted.Results: In 15 patients with EOPD, 22 variants were observed [PRKN, 9 (40.9%); PINK1, 10 (45.5%); and DJ1, 3 (13.6%)]. Three (13.6%) rare, nonsynonymous variants were identified, but no homozygous or compound heterozygous carriers were found. No exonic rearrangements were present in the three genes, and no carriers of SNCA genomic multiplications or LRRK2 p.G2019S were identified. The PINK1 p.R501Q functional analysis revealed pathogenic loss of function.Conclusion: More studies on age-related neurodegenerative diseases are needed in sub-Saharan African countries, including Nigeria. Population-specific variation may provide insight into the genes involved in PD in the local population but may also contribute to larger studiesperformed in White and Asian populations.
A Multidimensional Virtual Reality Neurorehabilitation Approach to Improve Functional Memory: Who Is the Ideal Candidate?
Authors: Di Tella Sonia , Isernia Sara , Pagliari Chiara , Jonsdottir Johanna , Castiglioni Carlotta , Gindri Patrizia , Gramigna Cristina , Canobbio Samuela , Salza Marco , Molteni Franco , Baglio Francesca 
Published: January 2021

Aims: We aimed to identify the significant predictors of ecological memory amelioration after the Human Empowerment Aging and Disability (HEAD) rehabilitation program, a multidimensional treatment for chronic neurological diseases.Materials and Methods: Ninety-three patients with Parkinson disease (n = 29), multiple sclerosis (n = 26), and stroke (n = 38) underwent a multidimensional rehabilitation. We focused on changes after treatment on ecological memory (outcome measure) evaluated by Rivermead Behavioral Memory Test, Third Edition (RBMT-3). Minimal clinically important difference (MCID) after treatment were calculated for RBMT-3. The change score on RBMT-3 was categorized in positive effect, stabilization, or no effect of the treatment. Random forest classification identified who significantly benefited from treatment against who did not in terms of ecological memory functioning. Accordingly, logistic regression models were created to identify the best predictors of the treatment effect. A predicted probability value was derived, and the profile of the ideal candidate of HEAD protocol was shown by combining different ranks of significant predictors in a 3 × 3 matrix for each pair of predictors.Results: A significant number of cases reported positive effect of the treatment on ecological memory, with an amelioration over the MCID or a stabilization. The random forest analysis highlighted a discrete accuracy of prediction (&gt;0.60) for all the variables considered at baseline for identifying participants who significantly benefited and who did not from the treatment. Significant logistic regression model (Wald method) showed a predictive role of Montreal Cognitive Assessment (MoCA; p = 0.007), 2-Minute Walk Test (2MWT; p = 0.038), and RBMT-3 (p &lt; 0.001) at baseline on HEAD treatment effect. Finally, we observed a high probability of success in people with higher residual cognitive functioning (MoCA; odds ratio = 1.306) or functional mobility (2MWT; odds ratio = 1.013).Discussion: The HEAD program is a rehabilitation with effects on multiple domains, including ecological memory. Residual level of cognitive and/or motor functioning is a significant predictor of the treatment success. These findings confirm the intrinsic relationship subsisting between motor and cognitive functions and suggest the beneficial effects of physical activity on cognitive functions and vice versa.
Changes in Retinal Structure and Ultrastructure in the Aged Mice Correlate With Differences in the Expression of Selected Retinal miRNAs
Authors: Hermenean Anca , Trotta Maria Consiglia , Gharbia Sami , Hermenean Andrei Gelu , Peteu Victor Eduard , Balta Cornel , Cotoraci Coralia , Gesualdo Carlo , Rossi Settimio , Gherghiceanu Mihaela , D’Amico Michele 
Published: January 2021

Age and gender are two important factors that may influence the function and structure of the retina and its susceptibility to retinal diseases. The aim of this study was to delineate the influence that biological sex and age exert on the retinal structural and ultrastructural changes in mice and to identify the age-related miRNA dysregulation profiles in the retina by gender. Experiments were undertaken on male and female Balb/c aged 24 months (approximately 75–85 years in humans) compared to the control (3 months). The retinas were analyzed by histology, transmission electron microscopy, and age-related miRNA expression profile analysis. Retinas of both sexes showed a steady decline in retinal thickness as follows: photoreceptor (PS) and outer layers (p &lt; 0.01 for the aged male vs. control; p &lt; 0.05 for the aged female vs. control); the inner retinal layers were significantly affected by the aging process in the males (p &lt; 0.01) but not in the aged females. Electron microscopy revealed more abnormalities which involve the retinal pigment epithelium (RPE) and Bruch’s membrane, outer and inner layers, vascular changes, deposits of amorphous materials, and accumulation of lipids or lipofuscins. Age-related miRNAs, miR-27a-3p (p &lt; 0.01), miR-27b-3p (p &lt; 0.05), and miR-20a-5p (p &lt; 0.05) were significantly up-regulated in aged male mice compared to the controls, whereas miR-20b-5p was significantly down-regulated in aged male (p &lt; 0.05) and female mice (p &lt; 0.05) compared to the respective controls. miR-27a-3p (5.00 fold; p &lt; 0.01) and miR-27b (7.58 fold; p &lt; 0.01) were significantly up-regulated in aged male mice vs. aged female mice, whereas miR-20b-5p (−2.10 fold; p &lt; 0.05) was significantly down-regulated in aged male mice vs. aged female mice. Interestingly, miR-27a-3p, miR-27b-3p, miR-20a-5p, and miR-20b-5p expressions significantly correlated with the thickness of the retinal PS layer (p &lt; 0.01), retinal outer layers (p &lt; 0.01), and Bruch’s membrane (p &lt; 0.01). Our results showed that biological sex can influence the structure and function of the retina upon aging, suggesting that this difference may be underlined by the dysregulation of age-related mi-RNAs.
Layered CMOS SPADs for Low Noise Detection of Charged Particles
Authors: Ratti Lodovico , Brogi Paolo , Collazuol Gianmaria , Dalla Betta Gian-Franco , Marrocchesi Pier Simone , Pancheri Lucio , Sulay Arta , Torilla Gianmarco , Vacchi Carla 
Published: January 2021

This paper reports the characterization of SPAD arrays fabricated in a 150 nm CMOS technology in view of applications to the detection of charged particles. The test vehicle contains SPADs with different active area and operated with different quenching techniques, either passive or active. The set of devices under test (DUTs) consists of single-tier chips, about 30 mm2 in area, with dual-tier structures where two chips are face-to-face bump bonded to each other. In the dual-layer structure obtained in this way, the coincidence signal between overlapping SPAD pairs is read out, with a beneficial impact on the dark count noise performance. The DUT characterization was mainly focused on studying the breakdown voltage in the single-layer arrays and the dark count rate (DCR), measured in different working conditions, in both the single- and the dual-layer structures. Comparison between the DCR performance of the two configurations clearly emphasizes the advantage of the coincidence readout architecture.
An Activated Potassium Phosphate Fertilizer Solution for Stimulating the Growth of Agricultural Plants
Authors: Belov Sergej V. , Danyleiko Yurij K. , Glinushkin Alexey P. , Kalinitchenko Valery P. , Egorov Alexey V. , Sidorov Vladimir A. , Konchekov Evgeny M. , Gudkov Sergey V. , Dorokhov Aleksey S. , Lobachevsky Yakov P. , Izmailov Andrey Yu 
Published: January 2021

This study aimed to develop a sustainable industrial chemical engineering technology to improve the interaction between technology, plants, and soil in agriculture. The signaling crosstalk between H2O2 and NO and that between H2O2 and Ca2+ influence plant developmental and physiological processes. Many promising technologies for crop stimulation and protection are based on a thorough study of the environmental impact of various physical factors. A low-temperature, high-frequency plasma was generated via cathode high-frequency glow discharge and used for the electrolysis of an aqueous solution of a low concentration of the strong electrolyte KH2PO4, with an electrolysis-activated solution named Plasmolite. The Plasmolite solution yielded a Raman (red) scattering spectrum with a maximum at 1,640 cm−1, which was associated with hydrogen atom vibrations, and other bands at 875, 930, 1,050, and 1,123 cm−1, which were associated with the aqueous electrolyte solution plasma treatment. Based on the goal of producing an optimal H2O2 concentration of 100 μM, two types of seeds were exposed to a Plasmolite-based 2 × 10–5 M KH2PO4 solution moisturizing medium for three days. Approximately 92% of the spring spelled seeds (grade “Gremme”) that were exposed to this test solution sprouted, compared with 76% of the seeds exposed to a control solution. The spring rye seeds (grade “Onokhoyskaya”) that were exposed to the test solution sprouted at a rate of 90% compared with 75% in the control. The percentage of seeds that sprouted with a root length of more than 6 mm was approximately 80% for the test solution, compared to 50% for the control. Based on these results, the use of Plasmolite is considered to be promising for the production of activated H2O2 for protecting plants and stimulating growth, particularly for enhancing the functions of K and P2O5 of fertilizers.
Characterization of the Temporal Pattern of Blood Protein Digestion in Rhodnius prolixus: First Description of Early and Late Gut Cathepsins
Authors: Henriques Bianca Santos , Gomes Bruno , Oliveira Pedro Lagerblad , Garcia Elói de Souza , Azambuja Patrícia , Genta Fernando Ariel 
Published: January 2021

Rhodnius prolixus is one important vector for the parasite Trypanosoma cruzi in Latin America, where Chagas disease is a significant health issue. Although R. prolixus is a model for investigations of vector–parasite interaction and transmission, not much has been done recently to further comprehend its protein digestion. In this work, gut proteolysis was characterized using new fluorogenic substrates, including optimum pH, inhibition profiles, and tissue and temporal expression patterns. Each protease possessed a particular tissue prevalence and activity cycle after feeding. Cathepsin L had a higher activity in the posterior midgut lumen, being characterized by a plateau of high activities during several days in the intermediate phase of digestion. Cathepsin D showed high activity levels in the tissue homogenates and in the luminal content of the posterior midgut, with a single peak 5 days after blood feeding. Aminopeptidases are highly associated with the midgut wall, where the highest activity is located. Assays with proteinaceous substrates as casein, hemoglobin, and serum albumin revealed different activity profiles, with some evidence of biphasic temporal proteolytic patterns. Cathepsin D genes are preferentially expressed in the anterior midgut, while cathepsin L genes are mainly located in the posterior portion of the midgut, with specific sets of genes being differently expressed in the initial, intermediate, or late phases of blood digestion.Significance StatementThis is the first description in a non-dipteran hematophagous species of a sequential protease secretion system based on midgut cathepsins instead of the most common insect digestive serine proteases (trypsins and chymotrypsins). The midgut of R. prolixus (Hemiptera) shows a different temporal expression of proteases in the initial, intermediate, and late stages of blood digestion. In this respect, a different timing in protease secretion may be an example of adaptative convergence in blood-sucking vectors from different orders. Expanding the knowledge about gut physiology in triatomine vectors may contribute to the development of new control strategies, aiming the blocking of parasite transmission.