bluuebunny/crossref_metadata_2025_split huggingface dataset:
From stress to depression: development of extracellular matrix-dependent cognitive impairment following social stress
Authors: Koskinen Maija-Kreetta , van Mourik Yvar , Smit August Benjamin , Riga Danai , Spijker Sabine 
Published: October 2020

AbstractStress can predispose to depressive episodes, yet the molecular mechanisms regulating the transition from the initial stress response to a persistent pathological depressive state remain poorly understood. We profiled the development of an enduring depressive-like state by assessing affective behavior and hippocampal function during the 2 months following social-defeat stress. We measured remodeling of hippocampal extracellular matrix (ECM) during this period, as we recently identified ECM changes to mediate cognitive impairment during the sustained depressive-like state. Affective disturbance and cognitive impairments develop disparately after social stress, with gradual appearance of affective deficits. In contrast, spatial memory was impaired both early after stress and during the late-emerging chronic depressive-like state, while intact in-between. Similarly, we observed a biphasic regulation of the hippocampal ECM coinciding with hippocampus-dependent memory deficits. Together our data (1) reveal a dichotomy between affective and cognitive impairments similar to that observed in patients, (2) indicate different molecular processes taking place during early stress and the chronic depressive-like state, and (3) support a role of the ECM in mediating long-lasting effects on memory. From a translational point of view, it is important to prioritize on temporal phenotypic aspects in animal models to elucidate the underlying mechanisms of depression.
Hyperactive sensorimotor cortex during voice perception in spasmodic dysphonia
Authors: Kanazawa Yuji , Kishimoto Yo , Tateya Ichiro , Ishii Toru , Sanuki Tetsuji , Hiroshiba Shinya , Aso Toshihiko , Omori Koichi , Nakamura Kimihiro 
Published: October 2020

AbstractSpasmodic dysphonia (SD) is characterized by an involuntary laryngeal muscle spasm during vocalization. Previous studies measured brain activation during voice production and suggested that SD arises from abnormal sensorimotor integration involving the sensorimotor cortex. However, it remains unclear whether this abnormal sensorimotor activation merely reflects neural activation produced by abnormal vocalization. To identify the specific neural correlates of SD, we used a sound discrimination task without overt vocalization to compare neural activation between 11 patients with SD and healthy participants. Participants underwent functional MRI during a two-alternative judgment task for auditory stimuli, which could be modal or falsetto voice. Since vocalization in falsetto is intact in SD, we predicted that neural activation during speech perception would differ between the two groups only for modal voice and not for falsetto voice. Group-by-stimulus interaction was observed in the left sensorimotor cortex and thalamus, suggesting that voice perception activates different neural systems between the two groups. Moreover, the sensorimotor signals positively correlated with disease severity of SD, and classified the two groups with 73% accuracy in linear discriminant analysis. Thus, the sensorimotor cortex and thalamus play a central role in SD pathophysiology and sensorimotor signals can be a new biomarker for SD diagnosis.
Seven novel genetic variants in a North Indian cohort with classical homocystinuria
Authors: Kaur Rajdeep , Attri Savita V. , Saini Arushi G. , Sankhyan Naveen , Singh Satwinder , Faruq Mohammed , Ramprasad V. L. , Sharda Sheetal , Murugan Sakthivel 
Published: October 2020

AbstractClassical homocystinuria is the most common cause of isolated homocystinuria. The variants of the CBS gene remain unidentified in Indian children with this disorder. Based on the hallmark clinical features, family history, and/or biochemical clues for classical homocystinuria, 16 children below the age of 18 years were evaluated by Sanger sequencing of the coding exons of CBS gene with flanking intronic regions. The common C677T variant of the MTHFR gene was also screened by restriction fragment length polymorphism. Fifteen children were clinically suspected of having classical homocystinuria and one asymptomatic child with positive family history. Only seven children had biochemical features of classical homocystinuria. Sanger sequencing of the CBS gene confirmed 15 different pathogenic or likely pathogenic variants in 14 cases. Of these, seven variants were novel (three frameshift deletions, two nonsense, one missense, one splice site variant) and were predicted to be deleterious by Mutation Taster software. Seven cases were homozygous, another six were compound heterozygous, and one case was single heterozygous in the study. None of the three most frequent mutations reported worldwide viz., I278T, G307S, and IVS 11-2A>C were found in our cohort. No variants were detected in the exons 2, 8, 12, and 14 as compared to reported literature. Eleven out of 15 variants were associated with the conserved catalytic domain of the CBS polypeptide. The MTHFR polymorphism C677T was observed in heterozygous state in six cases. Our study reports the detailed genotype and seven novel variants in the CBS gene, causing classical homocystinuria in Indian children. The genetic analysis will help to offer accurate genetic counseling, prenatal diagnosis, and development of mutation-based novel therapeutic strategies.
A critical evaluation of visual proportion of Gleason 4 and maximum cancer core length quantified by histopathologists
Authors: Carmona Echeverria Lina Maria , Haider Aiman , Freeman Alex , Stopka-Farooqui Urszula , Rosenfeld Avi , Simpson Benjamin S. , Hu Yipeng , Hawkes David , Pye Hayley , Heavey Susan , Stavrinides Vasilis , Norris Joseph M. , Bosaily Ahmed El-Shater , Cardona Barrena Cristina , Bott Simon , Brown Louise , Burns-Cox Nick , Dudderidge Tim , Henderson Alastair , Hindley Richard , Kaplan Richard , Kirkham Alex , Oldroyd Robert , Ghei Maneesh , Persad Raj , Punwani Shonit , Rosario Derek , Shergill Iqbal , Winkler Mathias , Ahmed Hashim U. , Emberton Mark , Whitaker Hayley C. 
Published: October 2020

AbstractGleason score 7 prostate cancer with a higher proportion of pattern 4 (G4) has been linked to genomic heterogeneity and poorer patient outcome. The current assessment of G4 proportion uses estimation by a pathologist, with a higher proportion of G4 more likely to trigger additional imaging and treatment over active surveillance. This estimation method has been shown to have inter-observer variability. Fifteen patients with Prostate Grade Group (GG) 2 (Gleason 3 + 4) and fifteen patients with GG3 (Gleason 4 + 3) disease were selected from the PROMIS study with 192 haematoxylin and eosin-stained slides scanned. Two experienced uropathologists assessed the maximum cancer core length (MCCL) and G4 proportion using the current standard method (visual estimation) followed by detailed digital manual annotation of each G4 area and measurement of MCCL (planimetric estimation) using freely available software by the same two experts. We aimed to compare visual estimation of G4 and MCCL to a pathologist-driven digital measurement. We show that the visual and digital MCCL measurement differs up to 2 mm in 76.6% (23/30) with a high degree of agreement between the two measurements; Visual gave a median MCCL of 10 ± 2.70 mm (IQR 4, range 5–15 mm) compared to digital of 9.88 ± 3.09 mm (IQR 3.82, range 5.01–15.7 mm) (p = 0.64) The visual method for assessing G4 proportion over-estimates in all patients, compared to digital measurements [median 11.2% (IQR 38.75, range 4.7–17.9%) vs 30.4% (IQR 18.37, range 12.9–50.76%)]. The discordance was higher as the amount of G4 increased (Bias 18.71, CI 33.87–48.75, r 0.7, p < 0.0001). Further work on assessing actual G4 burden calibrated to clinical outcomes might lead to the use of differing G4 thresholds of significance if the visual estimation is used or by incorporating semi-automated methods for G4 burden measurement.
Diel vertical migration into anoxic and high-pCO2 waters: acoustic and net-based krill observations in the Humboldt Current
Authors: Riquelme-Bugueño Ramiro , Pérez-Santos Iván , Alegría Nicolás , Vargas Cristian A. , Urbina Mauricio A. , Escribano Rubén 
Published: October 2020

AbstractA select group of marine organisms can enter the Oxygen Minimum Zones (OMZs) and even anoxic waters, while performing diel vertical migration (DVM). DVM of the euphausiid Euphausia eximia off northern Chile in the spring of 2015 was documented based on acoustic measurements using an echo sounder along with net samplings. Dissolved oxygen (DO) concentrations were obtained using a vertical profiler, and water samples were collected to obtain in situ nitrite (NO2−) concentrations as well as pHT, total alkalinity (AT), and therefore carbon dioxide partial pressure (pCO2) was estimated. Krill were found to migrate up to the surface (0–50 m) during the night and returned to ca. 200–300 m depth during the day, spending between 11 and 14 h at these layers. At the surface, DO and NO2− concentrations were 208 and 0.14 μM respectively, while pHT was 8.04 and 405 μatm pCO2. In contrast, at the deeper layers (200–300 m), DO and NO2− were < 3 and 6.3 μM respectively, with pHT 7.53 and 1490 μatm pCO2. The pHT and high pCO2 values at depths represent the conditions predicted for open ocean waters in a worst-case global warming scenario by 2150. The acoustic scatter suggested that > 60% of the krill swarms enter the OMZ and anoxic waters during the daytime. These frequent migrations suggest that krill can tolerate such extreme conditions associated with anoxic and high-pCO2 waters. The inferences drawn from the observation of these migrations might have strong implications for the current oceanic carbon pump models, highlighting the need for understanding the molecular and physiological adaptations allowing these migrations.
Reduced apparent fiber density in the white matter of premature-born adults
Authors: Menegaux Aurore , Hedderich Dennis M. , Bäuml Josef G. , Manoliu Andrei , Daamen Marcel , Berg Ronja C. , Preibisch Christine , Zimmer Claus , Boecker Henning , Bartmann Peter , Wolke Dieter , Sorg Christian , Stämpfli Philipp 
Published: October 2020

AbstractPremature-born adults exhibit lasting white matter alterations as demonstrated by widespread reduction in fractional anisotropy (FA) based on diffusion-weighted imaging (DWI). FA reduction, however, is non-specific for microscopic underpinnings such as aberrant myelination or fiber density (FD). Using recent advances in DWI, we tested the hypothesis of reduced FD in premature-born adults and investigated its link with the degree of prematurity and cognition. 73 premature- and 89 mature-born adults aged 25–27 years underwent single-shell DWI, from which a FD measure was derived using convex optimization modeling for microstructure informed tractography (COMMIT). Premature-born adults exhibited lower FD in numerous tracts including the corpus callosum and corona radiata compared to mature-born adults. These FD alterations were associated with both the degree of prematurity, as assessed via gestational age and birth weight, as well as with reduced cognition as measured by full-scale IQ. Finally, lower FD overlapped with lower FA, suggesting lower FD underlie unspecific FA reductions. Results provide evidence that premature birth leads to lower FD in adulthood which links with lower full-scale IQ. Data suggest that lower FD partly underpins FA reductions of premature birth but that other processes such as hypomyelination might also take place.
The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials
Authors: Asbaghi Omid , Sadeghian Mehdi , Nazarian Behzad , Sarreshtedari Mehrnoosh , Mozaffari-Khosravi Hassan , Maleki Vahid , Alizadeh Mohammad , Shokri Azad , Sadeghi Omid 
Published: October 2020

AbstractThe previous meta-analysis of clinical trials revealed a beneficial effect of vitamin E supplementation on serum C-reactive protein (CRP) concentrations; however, it is unknown whether this vitamin has the same influence on other inflammatory biomarkers. Also, several clinical trials have been published since the release of earlier meta-analysis. Therefore, we aimed to conduct a comprehensive meta-analysis to summarize current evidence on the effects of vitamin E supplementation on inflammatory biomarkers in adults. We searched the online databases using relevant keywords up to November 2019. Randomized clinical trials (RCTs) investigating the effect of vitamin E, compared with the placebo, on serum concentrations of inflammatory cytokines were included. Overall, we included 33 trials with a total sample size of 2102 individuals, aged from 20 to 70 years. Based on 36 effect sizes from 26 RCTs on serum concentrations of CRP, we found a significant reduction following supplementation with vitamin E (− 0.52, 95% CI − 0.80, − 0.23 mg/L, P < 0.001). Although the overall effect of vitamin E supplementation on serum concentrations of interleukin-6 (IL-6) was not significant, a significant reduction in this cytokine was seen in studies that used α-tocopherol and those trials that included patients with disorders related to insulin resistance. Moreover, we found a significant reducing effect of vitamin E supplementation on tumor necrosis factor-α (TNF-α) concentrations at high dosages of vitamin E; such that based on dose–response analysis, serum TNF-α concentrations were reduced significantly at the dosages of ≥ 700 mg/day vitamin E (Pnon-linearity = 0.001). Considering different chemical forms of vitamin E, α-tocopherol, unlike other forms, had a reducing effect on serum levels of CRP and IL-6. In conclusion, our findings revealed a beneficial effect of vitamin E supplementation, particularly in the form of α-tocopherol, on subclinical inflammation in adults. Future high-quality RCTs should be conducted to translate this anti-inflammatory effect of vitamin E to the clinical setting.
Differentiating Staphylococcus infection-associated glomerulonephritis and primary IgA nephropathy: a mass spectrometry-based exploratory study
Authors: Satoskar Anjali A. , Shapiro John P. , Jones Mikayla , Bott Cherri , Parikh Samir V. , Brodsky Sergey V. , Yu Lianbo , Nagaraja Haikady N. , Wilkey Daniel W. , Merchant Michael L. , Klein Jon B. , Nadasdy Tibor , Rovin Brad H. 
Published: October 2020

AbstractStaphylococcus infection-associated glomerulonephritis (SAGN) and primary IgA nephropathy (IgAN) are separate disease entities requiring different treatment approaches. However, overlapping histologic features may cause a diagnostic dilemma. An exploratory proteomic study to identify potential distinguishing biomarkers was performed on formalin fixed paraffin embedded kidney biopsy tissue, using mass spectrometry (HPLC–MS/MS) (n = 27) and immunohistochemistry (IHC) (n = 64), on four main diagnostic groups—SAGN, primary IgAN, acute tubular necrosis (ATN) and normal kidney (baseline transplant biopsies). Spectral counts modeled as a negative binomial distribution were used for statistical comparisons and in silico pathway analysis. Analysis of variance techniques were used to compare groups and the ROC curve to evaluate classification algorithms. The glomerular proteomes of SAGN and IgAN showed remarkable similarities, except for significantly higher levels of monocyte/macrophage proteins in SAGN—mainly lysozyme and S100A9. This finding was confirmed by IHC. In contrast, the tubulointerstitial proteomes were markedly different in IgAN and SAGN, with a lower abundance of metabolic pathway proteins and a higher abundance of extracellular matrix proteins in SAGN. The stress protein transglutaminase-2 (TGM2) was also significantly higher in SAGN. IHC of differentially-expressed glomerular and tubulointerstitial proteins can be used to help discriminate between SAGN and IgAN in ambiguous cases.
Differential expression of predisposing HLA-DQ2.5 alleles in DR5/DR7 celiac disease patients affects the pathological immune response to gluten
Authors: Pisapia Laura , Picascia Stefania , Farina Federica , Barba Pasquale , Gianfrani Carmen , Del Pozzo Giovanna 
Published: October 2020

AbstractThe DR5-DQ7/DR7-DQ2 genotype is very frequent among patients affected by celiac disease (CD), in Europe. This genotype, associated to high risk of CD, carries the HLA-DQA1*05and HLA-DQB1*02predisposing alleles, intransconfiguration. The alleles encode the DQ2.5 heterodimer responsible of gluten peptide presentation on the surface of antigen-presenting cells (APCs), and consequent pathogenic CD4+T cell activation. We demonstrated that DR5/DR7 APCs induce an anti-gluten CD4+T cell response, of comparable intensity to that observed with APCs carrying DR1/DR3 genotype, which risk alleles are incisconfiguration. In addition, we showed that DR5/DR7 APCs from celiac patients stimulated an effector CD4+T cell response higher with respect to that induced by DR5/DR7 APCs from healthy subjects. To explain these findings, we assessed the DQ2.5 RNA and protein quantity. We showed that the expression ofDQA1*05andDQB1*02risk alleles is much higher than the expression of non-CD-associated alleles, in agreement with the previous results obtained with DR1/DR3 genotype. The differential expression of transcripts influences the quantity of DQα1*05 and DQβ1*02 chains and, as consequence, the cell surface density of DQ2.5 heterodimers. Moreover, both RNA and proteins, are more abundant in APCs from celiac patients than controls. Finally, to unravel the mechanism regulating the expression of predisposingDQA1*05andDQB1*02alleles, we quantified the new synthetized RNA and found that the differential expression is explained by their transcription rate. Our results confirmed that the strength of antigen-specific CD4+T cell response is mainly determined by the amount of gluten in the diet and provided a new possible approach for a personalized diagnosis and for risk stratification.
Lacrimal gland excision in male and female mice causes ocular pain and anxiety-like behaviors
Authors: Mecum Neal E. , Demers Danielle , Sullivan Cara E. , Denis Tori E. , Kalliel John R. , Meng Ian D. 
Published: October 2020

AbstractLacrimal gland excision (LGE) induced dry eye produces more severe corneal damage in female mice, yet signs of LGE-induced ocular pain and anxiety in male and female mice have not been characterized. Excision of either the extraorbital gland (single LGE), or both the extraorbital and intraorbital glands (double LGE) was performed in male and female C57BL/6J mice to induce moderate and severe dry eye. Ongoing pain was assessed by quantifying palpebral opening and evoked nociceptive responses after corneal application of capsaicin and menthol. The open-field and plus maze were used to assess anxiety. Single LGE caused a reduction in palpebral opening and an increase in capsaicin and menthol-evoked responses only in female mice. Furthermore, single LGE produced signs of increased anxiety in female but not male mice. Overall, female mice appear more susceptible to signs of ocular pain, irritation, and anxiety in response to aqueous tear deficiency.
Physical properties of epilithic river biofilm as a new lead to perform pollution bioassessments in overseas territories
Authors: Monti Dominique , Hubas Cedric , Lourenço Xavier , Begarin Farid , Haouisée Alexandre , Romana Laurence , Lefrançois Estelle , Jestin Alexandra , Budzinski Hélène , Tapie Nathalie , Risser Théo , Mansot Jean-Louis , Keith Philippe , Gros Olivier , Lopez Pascal-Jean , Lauga Béatrice 
Published: October 2020

AbstractChlordecone (CLD) levels measured in the rivers of the French West Indies were among the highest values detected worldwide in freshwater ecosystems, and its contamination is recognised as a severe health, environmental, agricultural, economic, and social issue. In these tropical volcanic islands, rivers show strong originalities as simplified food webs, or numerous amphidromous migrating species, making the bioindication of contaminations a difficult issue. The objective of this study was to search for biological responses to CLD pollution in a spatially fixed and long-lasting component of the rivers in the West Indies: the epilithic biofilm. Physical properties were investigated through complementary analyses: friction, viscosity as well as surface adhesion were analyzed and coupled with measures of biofilm carbon content and exopolymeric substance (EPS) production. Our results have pointed out a mesoscale chemical and physical reactivity of the biofilm that can be correlated with CLD contamination. We were able to demonstrate that epilithic biofilm physical properties can effectively be used to infer freshwater environmental quality of French Antilles rivers. The friction coefficient is reactive to contamination and well correlated to carbon content and EPS production. Monitoring biofilm physical properties could offer many advantages to potential users in terms of effectiveness and ease of use, rather than more complex or time-consuming analyses.
A single dose of estrogen during hemorrhagic shock protects against Kidney Injury whereas estrogen restoration in ovariectomized mice is ineffective
Authors: Buléon Marie , Cuny Mélodie , Grellier Jimmy , Charles Pierre-Yves , Belliere Julie , Casemayou Audrey , Arnal Jean-François , Schanstra Joost-Peter , Tack Ivan 
Published: October 2020

AbstractThe protective effect of estrogens against chronic glomerular diseases is admitted but remains debated during acute kidney injury (AKI). Using a model of resuscitated hemorrhagic shock in C57/Bl6 female mice, this study evaluated at 1 and 21 days the renal effect of (1) endogenous estrogen, using ovariectomized mice with or without chronic estrogen restoration, or (2) exogenous estrogen, using a single administration of a pharmacological dose during shock resuscitation. In both ovariectomized and intact mice, hemorrhagic shock induced epithelial cell damages (assessed by KIM-1 renal expression) with secondary renal fibrosis but without significant decrease in GFR at day 21. Ovariectomy with or without estrogen restoration have no significant effect on renal damages and dysfunction. This lack of effect was associated with a marked (> 80%) reduction of total kidney GPR30 expression. By contrast, a single high dose of estradiol in intact mice reduced renal KIM-1 expression by 2/3, attenuated the severity of cell death related to pyroptosis, and prevented the increase of fibrosis by 1/3. This provides a rationale to investigate the benefits of a single administration of estrogen or estrogen modulators during acute kidney injuries in males. Furthermore, the cost/benefit ratio of such administration should be investigated in Human.