bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in neuronal excitability and synaptic transmission in nucleus accumbens in a transgenic Alzheimer’s disease mouse model
Authors: Fernández-Pérez E. J. , Gallegos S. , Armijo-Weingart L. , Araya A. , Riffo-Lepe N. O. , Cayuman F. , Aguayo L. G. 
Published: November 2020

AbstractSeveral previous studies showed that hippocampus and cortex are affected in Alzheimer’s disease (AD). However, other brain regions have also been found to be affected and could contribute with new critical information to the pathophysiological basis of AD. For example, volumetric studies in humans have shown a significant atrophy of the striatum, particularly in the nucleus Accumbens (nAc). The nAc is a key component of the limbic reward system and it is involved in cognition and emotional behaviors such as pleasure, fear, aggression and motivations, all of which are affected in neurodegenerative diseases such as AD. However, its role in AD has not been extensively studied. Therefore, using an AD mouse model, we investigated if the nAc was affected in 6 months old transgenic 2xTg (APP/PS1) mice. Immunohistochemistry (IHC) analysis in 2xTg mice showed increased intraneuronal Aβ accumulation, as well as occasional extracellular amyloid deposits detected through Thioflavin-S staining. Interestingly, the intracellular Aβ pathology was associated to an increase in membrane excitability in dissociated medium spiny neurons (MSNs) of the nAc. IHC and western blot analyses showed a decrease in glycine receptors (GlyR) together with a reduction in the pre- and post-synaptic markers SV2 and gephyrin, respectively, which correlated with a decrease in glycinergic miniature synaptic currents in nAc brain slices. Additionally, voltage-clamp recordings in dissociated MSNs showed a decrease in AMPA- and Gly-evoked currents. Overall, these results showed intracellular Aβ accumulation together with an increase in excitability and synaptic alterations in this mouse model. These findings provide new information that might help to explain changes in motivation, anhedonia, and learning in the onset of AD pathogenesis.
Clinical relevance and validity of TLICS system for thoracolumbar spine injury
Authors: Park Chan-Jin , Kim Sung-Kyu , Lee Tae-Min , Park Eric T. 
Published: November 2020

AbstractIn order to enhance the reliability of the application to clinical practice of the TLICS classification, we retrospectively reviewed the patients with thoracolumbar spine injuries who underwent magnetic resonance imaging (MRI) and analyzed the validity of the TLICS classification and the necessity of MRI. We enrolled 328 patients with thoracolumbar spine injury who underwent MRI. All patients were classified into conservative and operative treatment groups. The TLICS score of each group was analyzed and the degree of consistent with the recommended treatment through the TLICS classification was examined. Of the total 328 patients, 138 patients were treated conservatively and 190 patients were treated by surgery. Of the 138 patients who underwent conservative treatment, 131 patients (94.9%) had a TLICS score of 4 points or less, and matched with the recommendation score for conservative treatment according to the TLICS classification (match rate 94.9%, 131/138). Of the 190 patients who underwent operative treatment, 160 patients (84.2%) had a TLICS score of 4 points or more (match rate 84.2%, 160/190). All of 30 mismatched patients with a TLICS score of 3 points or less (15.8%) had stable burst fracture without neurological deficit. We retrospectively reviewed the validity of the TLICS classification for the injuries of the thoracolumbar spine, based on MRI in a large group of patients. Treatment with TLICS classification showed high validity, especially in conservative group, and MRI should be an essential diagnostic tool for accurate evaluation of posterior ligamentous complex injury.
SARS-CoV-2 receptor is co-expressed with elements of the kinin–kallikrein, renin–angiotensin and coagulation systems in alveolar cells
Authors: Sidarta-Oliveira Davi , Jara Carlos Poblete , Ferruzzi Adriano J. , Skaf Munir S. , Velander William H. , Araujo Eliana P. , Velloso Licio A. 
Published: November 2020

AbstractSARS-CoV-2, the pathogenic agent of COVID-19, employs angiotensin converting enzyme-2 (ACE2) as its cell entry receptor. Clinical data reveal that in severe COVID-19, SARS-CoV-2 infects the lung, leading to a frequently lethal triad of respiratory insufficiency, acute cardiovascular failure, and coagulopathy. Physiologically, ACE2 plays a role in the regulation of three systems that could potentially be involved in the pathogenesis of severe COVID-19: the kinin–kallikrein system, resulting in acute lung inflammatory edema; the renin–angiotensin system, promoting cardiovascular instability; and the coagulation system, leading to thromboembolism. Here we assembled a healthy human lung cell atlas meta-analysis with ~ 130,000 public single-cell transcriptomes and show that key elements of the bradykinin, angiotensin and coagulation systems are co-expressed with ACE2 in alveolar cells and associated with their differentiation dynamics, which could explain how changes in ACE2 promoted by SARS-CoV-2 cell entry result in the development of the three most severe clinical components of COVID-19.
A novel Trypanosoma cruzi secreted antigen as a potential biomarker of Chagas disease
Authors: Nagarkatti Rana , Acosta David , Acharyya Nirmallya , de Araujo Fernanda Fortes , Elói-Santos Silvana Maria , Martins-Filho Olindo Assis , Teixeira-Carvalho Andréa , Debrabant Alain 
Published: November 2020

AbstractChagas drug discovery has been hampered by a lack of validated assays to establish treatment efficacy in pre-clinical animal models and in patients infected with T. cruzi. Reduced levels of parasite secreted antigens in the blood of infected hosts could be used to demonstrate treatment efficacy. A published proteomic study of parasite secreted antigens identified the hypothetical protein Tc_5171 as a secreted antigen. In this report, we developed Tc_5171 specific antibodies and showed that the native protein was expressed by the three life cycle stages of the parasite. Anti-peptide antibodies were able to detect the parasite antigen in blood of infected mice during the acute and the chronic phase of infection. Benznidazole treatment of infected mice significantly reduced their blood antigen levels. Of clinical significance, patients diagnosed with Chagas disease, either asymptomatic or with cardiac clinical symptoms had significantly higher Tc_5171 antigen levels compared to endemic controls. Pair-wise analysis, before and after Benznidazole treatment, of patients with asymptomatic Chagas disease showed a significant reduction in antigen levels post treatment. Taken together, our results indicate that Tc_5171 could be used as a novel biomarker of Chagas disease for diagnosis and to assess treatment efficacy.
Gene expression signatures associated with sensitivity to azacitidine in myelodysplastic syndromes
Authors: Kim Kyuryung , Park Silvia , Choi Hayoung , Kim Hye Joung , Kwon Yong-Rim , Ryu Daeun , Kim Myungshin , Kim Tae-Min , Kim Yoo-Jin 
Published: November 2020

AbstractAllogeneic stem cell transplantation is currently the only curative treatment option for myelodysplastic syndromes (MDS). Pre-transplant debulking treatment have been employed for advanced MDS and we previously reported that marrow response (blast ≤ 5%) following the bridging therapy with hypomethylating agent was an independent favorable factor for survival; however, it is still not clear which patients will respond to hypomethylating agent and which genomic features can predict the response. In this study, we performed RNAseq for 23 MDS patients among which 14 (61%) and 9 (39%) patients showed marrow complete remission and primary resistance to azacitidine, respectively. Differential expression-based analyses of treatment-naive, baseline gene expression profiles revealed that molecular functions representing mitochondria and apoptosis were up-regulated in responders. In contrast, we identified genes involved in the Wnt pathway were relatively up-regulated in non-responders. In independent validation cohorts of MDS patients, the expression of gene sets specific to non-responders and responders distinguished the patients with favorable prognosis and those responded to azacitidine highlighting the prognostic and predictive implication. In addition, a systems biology approach identified genes involved in ubiquitination, such as UBC and PFDN2, which may be key players in the regulation of differential gene expression in treatment responders and non-responders. Taken together, identifying the gene expression signature may advance our understanding of the molecular mechanisms of azacitidine and may also serve to predict patient responses to drug treatment.
Exploring blood alterations in chronic kidney disease and haemodialysis using metabolomics
Authors: Gagnebin Yoric , Jaques David A. , Rudaz Serge , de Seigneux Sophie , Boccard Julien , Ponte Belén 
Published: November 2020

AbstractChronic kidney disease (CKD) is characterized by retention of uremic solutes. Compared to patients with non-dialysis dependent CKD, those requiring haemodialysis (HD) have increased morbidity and mortality. We wished to characterise metabolic patterns in CKD compared to HD patients using metabolomics. Prevalent non-HD CKD KDIGO stage 3b–4 and stage 5 HD outpatients were screened at a single tertiary hospital. Various liquid chromatography approaches hyphenated with mass spectrometry were used to identify 278 metabolites. Unsupervised and supervised data analyses were conducted to characterize metabolic patterns. 69 patients were included in the CKD group and 35 in the HD group. Unsupervised data analysis showed clear clustering of CKD, pre-dialysis (preHD) and post-dialysis (postHD) patients. Supervised data analysis revealed qualitative as well as quantitative differences in individual metabolites profiles between CKD, preHD and postHD states. An original metabolomics framework could discriminate between CKD stages and highlight HD effect based on 278 identified metabolites. Significant differences in metabolic patterns between CKD and HD patients were found overall as well as for specific metabolites. Those findings could explain clinical discrepancies between patients requiring HD and those with earlier stage of CKD.
Similar cognitive deficits in mice and humans in the chronic phase post-stroke identified using the touchscreen-based paired-associate learning task
Authors: Chow Wei Zhen , Ong Lin Kooi , Kluge Murielle G. , Gyawali Prajwal , Walker Frederick R. , Nilsson Michael 
Published: November 2020

AbstractFor many chronic stroke survivors, persisting cognitive dysfunction leads to significantly reduced quality of life. Translation of promising therapeutic strategies aimed at improving cognitive function is hampered by existing, disparate cognitive assessments in animals and humans. In this study, we assessed post-stroke cognitive function using a comparable touchscreen-based paired-associate learning task in a cross-sectional population of chronic stroke survivors (≥ 5 months post-stroke, n = 70), age-matched controls (n = 70), and in mice generated from a C57BL/6 mouse photothrombotic stroke model (at six months post-stroke). Cognitive performance of stroke survivors was analysed using linear regression adjusting for age, gender, diabetes, systolic blood pressure and waist circumference. Stroke survivors made significantly fewer correct choices across all tasks compared with controls. Similar cognitive impairment was observed in the mice post-stroke with fewer correct choices compared to shams. These results highlight the feasibility and potential value of analogous modelling of clinically meaningful cognitive impairments in chronic stroke survivors and in mice in chronic phase after stroke. Implementation of validated, parallel cross-species test platforms for cognitive assessment offer the potential of delivering a more useful framework for evaluating therapies aimed at improving long-term cognitive function post-stroke.
Deacidification by FhlA-dependent hydrogenase is involved in urease activity and urinary stone formation in uropathogenic Proteus mirabilis
Authors: Lin Wen-Yuan , Liaw Shwu-Jen 
Published: November 2020

AbstractProteus mirabilis is an important uropathogen, featured with urinary stone formation. Formate hydrogenlyase (FHL), consisting of formate dehydrogenase H and hydrogenase for converting proton to hydrogen, has been implicated in virulence. In this study, we investigated the role of P. mirabilis FHL hydrogenase and the FHL activator, FhlA. fhlA and hyfG (encoding hydrogenase large subunit) displayed a defect in acid resistance. fhlA and hyfG mutants displayed a delay in medium deacidification compared to wild-type and ureC mutant failed to deacidify the medium. In addition, loss of fhlA or hyfG decreased urease activity in the pH range of 5–8. The reduction of urease activities in fhlA and hyfG mutants subsided gradually over the pH range and disappeared at pH 9. Furthermore, mutation of fhlA or hyfG resulted in a decrease in urinary stone formation in synthetic urine. These indicate fhlA- and hyf-mediated deacidification affected urease activity and stone formation. Finally, fhlA and hyfG mutants exhibited attenuated colonization in mice. Altogether, we found expression of fhlA and hyf confers medium deacidification via facilitating urease activity, thereby urinary stone formation and mouse colonization. The link of acid resistance to urease activity provides a potential strategy for counteracting urinary tract infections by P. mirabilis.
Gut microbiota depletion by chronic antibiotic treatment alters the sleep/wake architecture and sleep EEG power spectra in mice
Authors: Ogawa Yukino , Miyoshi Chika , Obana Nozomu , Yajima Kaho , Hotta-Hirashima Noriko , Ikkyu Aya , Kanno Satomi , Soga Tomoyoshi , Fukuda Shinji , Yanagisawa Masashi 
Published: November 2020

AbstractDysbiosis of the gut microbiota affects physiological processes, including brain functions, by altering the intestinal metabolism. Here we examined the effects of the gut microbiota on sleep/wake regulation. C57BL/6 male mice were treated with broad-spectrum antibiotics for 4 weeks to deplete their gut microbiota. Metabolome profiling of cecal contents in antibiotic-induced microbiota-depleted (AIMD) and control mice showed significant variations in the metabolism of amino acids and vitamins related to neurotransmission, including depletion of serotonin and vitamin B6, in the AIMD mice. Sleep analysis based on electroencephalogram and electromyogram recordings revealed that AIMD mice spent significantly less time in non-rapid eye movement sleep (NREMS) during the light phase while spending more time in NREMS and rapid eye movement sleep (REMS) during the dark phase. The number of REMS episodes seen in AIMD mice increased during both light and dark phases, and this was accompanied by frequent transitions from NREMS to REMS. In addition, the theta power density during REMS was lower in AIMD mice during the light phase compared with that in the controls. Consequently, the gut microbiota is suggested to affect the sleep/wake architecture by altering the intestinal balance of neurotransmitters.
Considerations on the human Achilles tendon moment arm for in vivo triceps surae muscle–tendon unit force estimates
Authors: Holzer Denis , Paternoster Florian Kurt , Hahn Daniel , Siebert Tobias , Seiberl Wolfgang 
Published: November 2020

AbstractMoment arm-angle functions (MA-a-functions) are commonly used to estimate in vivo muscle forces in humans. However, different MA-a-functions might not only influence the magnitude of the estimated muscle forces but also change the shape of the muscle’s estimated force-angle relationship (F-a-r). Therefore, we investigated the influence of different literature based Achilles tendon MA-a-functions on the triceps surae muscle–tendon unit F-a-r. The individual in vivo triceps torque–angle relationship was determined in 14 participants performing maximum voluntary fixed-end plantarflexion contractions from 18.3° ± 3.2° plantarflexion to 24.2° ± 5.1° dorsiflexion on a dynamometer. The resulting F-a-r were calculated using 15 literature-based in vivo Achilles tendon MA-a-functions. MA-a-functions affected the F-a-r shape and magnitude of estimated peak active triceps muscle–tendon unit force. Depending on the MA-a-function used, the triceps was solely operating on the ascending limb (n = 2), on the ascending limb and plateau region (n = 12), or on the ascending limb, plateau region and descending limb of the F-a-r (n = 1). According to our findings, the estimated triceps muscle–tendon unit forces and the shape of the F-a-r are highly dependent on the MA-a-function used. As these functions are affected by many variables, we recommend using individual Achilles tendon MA-a-functions, ideally accounting for contraction intensity-related changes in moment arm magnitude.
A comparison of inflammation markers for predicting oncological outcomes after surgical resection of non-small-cell lung cancer: a validated analysis of 2,066 patients
Authors: Wu Hsiang-Ling , Wu Yu-Ming , Chen Jui-Tai , Chang Kuang-Yi , Cherng Yih-Giun , Lin Shih-Pin , Tsou Mei-Yung , Tai Ying-Hsuan 
Published: November 2020

AbstractClinical and pathological predictors have proved to be insufficient in identifying high-risk patients who develop cancer recurrence after tumour resection. We aimed to compare the prognostic ability of various inflammation markers in patients undergoing surgical resection of lung cancer. We consecutively included 2,066 patients with stage I–III non-small-cell lung cancer undergoing surgical resection at the center between 2005 and 2015. We evaluated prognostic nutritional index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio along with their perioperative changes. We conducted stepwise backward variable elimination and internal validation to compare the selected markers’ predictive performance for postoperative recurrence-free survival and overall survival. Preoperative neutrophil-to-lymphocyte ratio independently predicts recurrence-free survival (HR: 1.267, 95% CI 1.064–1.509, p = 0.0079, on base-2 logarithmic scale) and overall survival (HR: 1.357, 95% CI 1.070–1.721, p = 0.0117, on base-2 logarithmic scale). The cut-off value is 2.3 for predicting both recurrence (sensitivity: 46.1% and specificity: 66.7%) and mortality (sensitivity: 84.2% and specificity: 40.4%). Advanced cancer stage, poor tumour differentiation, and presence of perineural infiltration were significantly correlated with higher preoperative neutrophil-to-lymphocyte ratio. We concluded that preoperative neutrophil-to-lymphocyte ratio is superior to prognostic nutritional index and platelet-to-lymphocyte ratio in predicting postoperative recurrence and mortality of patients undergoing surgical resection of non-small-cell lung cancer.
Predictive modeling of proliferative vitreoretinopathy using automated machine learning by ophthalmologists without coding experience
Authors: Antaki Fares , Kahwati Ghofril , Sebag Julia , Coussa Razek Georges , Fanous Anthony , Duval Renaud , Sebag Mikael 
Published: November 2020

AbstractWe aimed to assess the feasibility of machine learning (ML) algorithm design to predict proliferative vitreoretinopathy (PVR) by ophthalmologists without coding experience using automated ML (AutoML). The study was a retrospective cohort study of 506 eyes who underwent pars plana vitrectomy for rhegmatogenous retinal detachment (RRD) by a single surgeon at a tertiary-care hospital between 2012 and 2019. Two ophthalmologists without coding experience used an interactive application in MATLAB to build and evaluate ML algorithms for the prediction of postoperative PVR using clinical data from the electronic health records. The clinical features associated with postoperative PVR were determined by univariate feature selection. The area under the curve (AUC) for predicting postoperative PVR was better for models that included pre-existing PVR as an input. The quadratic support vector machine (SVM) model built using all selected clinical features had an AUC of 0.90, a sensitivity of 63.0%, and a specificity of 97.8%. An optimized Naïve Bayes algorithm that did not include pre-existing PVR as an input feature had an AUC of 0.81, a sensitivity of 54.3%, and a specificity of 92.4%. In conclusion, the development of ML models for the prediction of PVR by ophthalmologists without coding experience is feasible. Input from a data scientist might still be needed to tackle class imbalance—a common challenge in ML classification using real-world clinical data.
Sex-dependent differences in single-leg squat kinematics and their relationship to squat depth in physically active individuals
Authors: Zawadka Magdalena , Smolka Jakub , Skublewska-Paszkowska Maria , Lukasik Edyta , Bys Aleksandra , Zielinski Grzegorz , Gawda Piotr 
Published: November 2020

AbstractThe purpose of this study is to compare recreationally physically active females and males with regard to spine, pelvis and lower limb joints peak angles in each plane of motion during a single leg squat (SLS). The second aim is to investigate the relationship between kinematics and SLS depth in females and males. Fifty-eight healthy, young adults performed 5 repetitions of a single right leg squat to maximal depth while keeping their balance. Kinematic data were obtained using an optical motion capture system. At the hip, greater adduction and greater internal rotation were observed in females than in males. Females had more extended spines and less outward bended knees throughout the SLS than did men. In males, squat depth was significantly, positively correlated with the maximal angle of the ankle (r = 0.60, p < 0.001), the knee (r = 0.87, p < 0.001), the hip (r = 0.73, p < 0.001) and the pelvis (r = 0.40, p = 0.02) in the sagittal plane. A positive significant correlation was found between SLS depth and maximal angle of the knee (r = 0.88, p < 0.001) and the ankle (r = 0.53, p = 0.01) in the sagittal plane in females. Males and females used different motor strategies at all levels of the kinematic chain during SLS.
Overexpression of OsCM alleviates BLB stress via phytohormonal accumulation and transcriptional modulation of defense-related genes in Oryza sativa
Authors: Jan Rahmatullah , Khan Muhammad Aaqil , Asaf Sajjad , Lee In-Jung , Bae Jong-Sup , Kim Kyung-Min 
Published: November 2020

AbstractXanthomonas oryzae is a serious pathogen causing bacterial leaf blight (BLB) disease in rice, markedly reducing its yield. In this study, the rice chorismate mutase (OsCM) gene was overexpressed in a bacterial leaf blight-susceptible rice line to investigate the functional role of OsCM in response to bacterial leaf blight stress. We reported that overexpression of OsCM altered the downstream pathway of aromatic amino acids, mitigating pathogen stress by altering stress-responsive genes and hormonal accumulation. Phenotypic evaluation showed that the lesion length in the transgenic line was significantly lesser than that in the wild-type, suggesting greater resistance in the transgenic line. Further analysis revealed that OsCM expression induced phenylalanine accumulation and suppressed tyrosine accumulation in response to bacterial leaf blight stress. Furthermore, bacterial leaf blight stress induced genes downstream of the phenylpropanoid pathway in conjunction with OsCM, suggesting that the phenylpropanoid pathway is dependent on OsCM gene expression. We reported high SA and low JA accumulation in response to bacterial leaf blight stress in the transgenic line. This higher SA accumulation suggested that SA induces immune responses by functioning as a promoter of nonexpresser pathogenesis-related genes 1 (NPR1) transcriptional regulation. Xa7 expression was induced with increase in nonexpresser pathogenesis-related genes 1, which is thought to be responsible for Xa7 expression, which is responsible for mitigating bacterial leaf blight stress.