bluuebunny/crossref_metadata_2025_split huggingface dataset:
The composition of human vaginal microbiota transferred at birth affects offspring health in a mouse model
Authors: Jašarević Eldin , Hill Elizabeth M. , Kane Patrick J. , Rutt Lindsay , Gyles Trevonn , Folts Lillian , Rock Kylie D. , Howard Christopher D. , Morrison Kathleen E. , Ravel Jacques , Bale Tracy L. 
Published: November 2021

AbstractNewborns are colonized by maternal microbiota that is essential for offspring health and development. The composition of these pioneer communities exhibits individual differences, but the importance of this early-life heterogeneity to health outcomes is not understood. Here we validate a human microbiota-associated model in which fetal mice are cesarean delivered and gavaged with defined human vaginal microbial communities. This model replicates the inoculation that occurs during vaginal birth and reveals lasting effects on offspring metabolism, immunity, and the brain in a community-specific manner. This microbial effect is amplified by prior gestation in a maternal obesogenic or vaginal dysbiotic environment where placental and fetal ileum development are altered, and an augmented immune response increases rates of offspring mortality. Collectively, we describe a translationally relevant model to examine the defined role of specific human microbial communities on offspring health outcomes, and demonstrate that the prenatal environment dramatically shapes the postnatal response to inoculation.
Bridging the gap between in silico and in vivo by modeling opioid disposition in a kidney proximal tubule microphysiological system
Authors: Imaoka Tomoki , Huang Weize , Shum Sara , Hailey Dale W. , Chang Shih-Yu , Chapron Alenka , Yeung Catherine K. , Himmelfarb Jonathan , Isoherranen Nina , Kelly Edward J. 
Published: November 2021

AbstractOpioid overdose, dependence, and addiction are a major public health crisis. Patients with chronic kidney disease (CKD) are at high risk of opioid overdose, therefore novel methods that provide accurate prediction of renal clearance (CLr) and systemic disposition of opioids in CKD patients can facilitate the optimization of therapeutic regimens. The present study aimed to predict renal clearance and systemic disposition of morphine and its active metabolite morphine-6-glucuronide (M6G) in CKD patients using a vascularized human proximal tubule microphysiological system (VPT-MPS) coupled with a parent-metabolite full body physiologically-based pharmacokinetic (PBPK) model. The VPT-MPS, populated with a human umbilical vein endothelial cell (HUVEC) channel and an adjacent human primary proximal tubular epithelial cells (PTEC) channel, successfully demonstrated secretory transport of morphine and M6G from the HUVEC channel into the PTEC channel. The in vitro data generated by VPT-MPS were incorporated into a mechanistic kidney model and parent-metabolite full body PBPK model to predict CLr and systemic disposition of morphine and M6G, resulting in successful prediction of CLr and the plasma concentration–time profiles in both healthy subjects and CKD patients. A microphysiological system together with mathematical modeling successfully predicted renal clearance and systemic disposition of opioids in CKD patients and healthy subjects.
Association between prognostic factors and the outcomes of patients infected with SARS-CoV-2 harboring multiple spike protein mutations
Authors: Gunadi  , Hakim Mohamad Saifudin , Wibawa Hendra , Marcellus  , Trisnawati Ika , Supriyati Endah , Afiahayati  , Khair Riat El , Iskandar Kristy , Siswanto  , Irene  , Anggorowati Nungki , Daniwijaya Edwin Widyanto , Nugrahaningsih Dwi Aris Agung , Puspadewi Yunika , Simanjaya Susan , Puspitarani Dyah Ayu , Hanifin Hana Fauzyyah , Setiawan Alvina Alexandra , Tania Irene , Amalia Cita Shafira , Artayasa I. Putu Aditio , Rachman Haries , Mulyawan Herdiyanto , Ananda Nur Rahmi , Arguni Eggi , Nuryastuti Titik , Wibawa Tri 
Published: November 2021

AbstractThe outcome of SARS-CoV-2 infection is determined by multiple factors, including the viral, host genetics, age, and comorbidities. This study investigated the association between prognostic factors and disease outcomes of patients infected by SARS-CoV-2 with multiple S protein mutations. Fifty-one COVID-19 patients were recruited in this study. Whole-genome sequencing of 170 full-genomes of SARS-CoV-2 was conducted with the Illumina MiSeq sequencer. Most patients (47%) had mild symptoms of COVID-19 followed by moderate (19.6%), no symptoms (13.7%), severe (4%), and critical (2%). Mortality was found in 13.7% of the COVID-19 patients. There was a significant difference between the age of hospitalized patients (53.4 ± 18 years) and the age of non-hospitalized patients (34.6 ± 19) (p = 0.001). The patients’ hospitalization was strongly associated with hypertension, diabetes, and anticoagulant and were strongly significant with the OR of 17 (95% CI 2–144; p = 0.001), 4.47 (95% CI 1.07–18.58; p = 0.039), and 27.97 (95% CI 1.54–507.13; p = 0.02), respectively; while the patients’ mortality was significantly correlated with patients’ age, anticoagulant, steroid, and diabetes, with OR of 8.44 (95% CI 1.5–47.49; p = 0.016), 46.8 (95% CI 4.63–472.77; p = 0.001), 15.75 (95% CI 2–123.86; p = 0.009), and 8.5 (95% CI 1.43–50.66; p = 0.019), respectively. This study found the clade: L (2%), GH (84.3%), GR (11.7%), and O (2%). Besides the D614G mutation, we found L5F (18.8%), V213A (18.8%), and S689R (8.3%). No significant association between multiple S protein mutations and the patients’ hospitalization or mortality. Multivariate analysis revealed that hypertension and anticoagulant were the significant factors influencing the hospitalization and mortality of patients with COVID-19 with an OR of 17.06 (95% CI 2.02–144.36; p = 0.009) and 46.8 (95% CI 4.63–472.77; p = 0.001), respectively. Moreover, the multiple S protein mutations almost reached a strong association with patients’ hospitalization (p = 0.07). We concluded that hypertension and anticoagulant therapy have a significant impact on COVID-19 outcomes. This study also suggests that multiple S protein mutations may impact the COVID-19 outcomes. This further emphasized the significance of monitoring SARS-CoV-2 variants through genomic surveillance, particularly those that may impact the COVID-19 outcomes.
Intrinsic timescales across the basal ganglia
Authors: Nougaret Simon , Fascianelli Valeria , Ravel Sabrina , Genovesio Aldo 
Published: November 2021

AbstractRecent studies have shown that temporal stability of the neuronal activity over time can be estimated by the structure of the spike-count autocorrelation of neuronal populations. This estimation, called the intrinsic timescale, has been computed for several cortical areas and can be used to propose a cortical hierarchy reflecting a scale of temporal receptive windows between areas. In this study, we performed an autocorrelation analysis on neuronal populations of three basal ganglia (BG) nuclei, including the striatum and the subthalamic nucleus (STN), the input structures of the BG, and the external globus pallidus (GPe). The analysis was performed during the baseline period of a motivational visuomotor task in which monkeys had to apply different amounts of force to receive different amounts of reward. We found that the striatum and the STN have longer intrinsic timescales than the GPe. Moreover, our results allow for the placement of these subcortical structures within the already-defined scale of cortical temporal receptive windows. Estimates of intrinsic timescales are important in adding further constraints in the development of computational models of the complex dynamics among these nuclei and throughout cortico-BG-thalamo-cortical loops.
Synbiotic (Lactiplantibacillus pentosus GSSK2 and isomalto-oligosaccharides) supplementation modulates pathophysiology and gut dysbiosis in experimental metabolic syndrome
Authors: Khanna Sakshi , Bishnoi Mahendra , Kondepudi Kanthi Kiran , Shukla Geeta 
Published: November 2021

AbstractMetabolic syndrome a lifestyle disease, where diet and gut microbiota play a prodigious role in its initiation and progression. Prophylactic bio-interventions employing probiotics and prebiotics offer an alternate nutritional approach towards attenuating its progression. The present study aimed to evaluate the protective efficacy of a novel synbiotic (Lactiplantibacillus pentosus GSSK2 + isomalto-oligosaccharides) in comparison to orlistat in an experimental model of metabolic syndrome. It was observed that supplementation of synbiotic for 12 weeks to Sprague Dawley rats fed with high fat diet (HFD), ameliorated the morphometric parameters i.e. weight gain, abdominal circumference, Lee’s index, BMI and visceral fat deposition along with significantly increased fecal Bacteroidetes to Firmicutes ratio, elevated population of Lactobacillus spp., Akkermansia spp., Faecalibacterium spp., Roseburia spp. and decreased Enterobacteriaceae compared with HFD animals. Additionally, synbiotic administration to HFD animals exhibited improved glucose clearance, lipid biomarkers, alleviated oxidative stress, prevented leaky gut phenotype, reduced serum lipopolysaccharides and modulated the inflammatory, lipid and glucose metabolism genes along with restored histomorphology of adipose tissue, colon and liver compared with HFD animals. Taken together, the study highlights the protective potential of synbiotic in comparison with its individual components in ameliorating HFD-induced metabolic complications.
Gait performance of adolescent mice assessed by the CatWalk XT depends on age, strain and sex and correlates with speed and body weight
Authors: Pitzer Claudia , Kurpiers Barbara , Eltokhi Ahmed 
Published: November 2021

AbstractThe automatization of behavioral tests assessing motor activity in rodent models is important for providing robust and reproducible results and evaluating new therapeutics. The CatWalk system is an observer-independent, automated and computerized technique for the assessment of gait performance in rodents. This method has previously been used in adult rodent models of CNS-based movement disorders such as Parkinson’s and Huntington’s diseases. As motor and gait abnormalities in neuropsychiatric disorders are observed during infancy and adolescence, it became important to validate the CatWalk XT in the gait analysis of adolescent mice and unravel factors that may cause variations in gait performance. Three adolescent wild-type inbred mouse strains, C57BL/6N, DBA/2 and FVB/N, were tested using the CatWalk XT (Version 10.6) for suitable detection settings to characterize several gait parameters at P32 and P42. The same detection settings being suitable for C57BL/6N and DBA/2 mice allowed a direct comparison between the two strains. On the other hand, due to their increased body weight and size, FVB/N mice required different detection settings. The CatWalk XT reliably measured the temporal, spatial, and interlimb coordination parameters in the investigated strains during adolescence. Additionally, significant effects of sex, development, speed and body weight within each strain confirmed the sensitivity of motor and gait functions to these factors. The CatWalk gait analysis of rodents during adolescence, taking the effect of age, strain, sex, speed and body weight into consideration, will decrease intra-laboratory discrepancies and increase the face validity of rodent models of neuropsychiatric disorders.
Women and other risk factors for chronic kidney disease of unknown etiology in Thailand: National Health Examination V Survey
Authors: Aekplakorn Wichai , Chariyalertsak Suwat , Kessomboon Pattapong , Assanangkornchai Sawitri , Taneepanichskul Surasak , Neelapaichit Nareemarn , Chittamma Anchalee , Kitiyakara Chagriya 
Published: November 2021

AbstractThere are limited data on chronic kidney disease of unknown etiology (CKDu) from Southeast Asia. Initially described in working age men, a common approach to detect CKDu that includes all adults has recently been proposed. We determined the prevalence, and risk factors for CKDu using data from a cross-sectional, nationally representative survey of the adult population of Thailand. We used a proxy for CKDu as age < 70 with impaired kidney function (eGFR < 60) in the absence of diabetes and hypertension (CKDu1) and heavy proteinuria (CKDu2). Prevalence estimates were probability-weighted for the Thai population. The associations between risk factors and CKDu or elderly subjects with eGFR < 60 without traditional causes were assessed by multivariable logistic regression. Of 17,329 subjects, the prevalence were: eGFR < 60, 5.3%; CKDu1 0.78%; CKDu2, 0.75%. CKDu differed by 4.3-folds between regions. Women, farmers/laborers, older age, gout, painkillers, rural area, and stones were independent risk factors for CKDu. Women, age, rural, gout, painkillers were significant risk factors for both CKDu and elderly subjects. These data collected using standardized methodology showed that the prevalence of CKDu in Thailand was low overall, although some regions had higher risk. Unlike other countries, Thai women had a two-fold higher risk of CKDu.
Probabilistic modelling of effects of antibiotics and calendar time on transmission of healthcare-associated infection
Authors: Laager Mirjam , Cooper Ben S. , Eyre David W. ,   the CDC Modeling Infectious Diseases in Healthcare Program (MInD-Healthcare)
Published: November 2021

AbstractHealthcare-associated infection and antimicrobial resistance are major concerns. However, the extent to which antibiotic exposure affects transmission and detection of infections such as MRSA is unclear. Additionally, temporal trends are typically reported in terms of changes in incidence, rather than analysing underling transmission processes. We present a data-augmented Markov chain Monte Carlo approach for inferring changing transmission parameters over time, screening test sensitivity, and the effect of antibiotics on detection and transmission. We expand a basic model to allow use of typing information when inferring sources of infections. Using simulated data, we show that the algorithms are accurate, well-calibrated and able to identify antibiotic effects in sufficiently large datasets. We apply the models to study MRSA transmission in an intensive care unit in Oxford, UK with 7924 admissions over 10 years. We find that falls in MRSA incidence over time were associated with decreases in both the number of patients admitted to the ICU colonised with MRSA and in transmission rates. In our inference model, the data were not informative about the effect of antibiotics on risk of transmission or acquisition of MRSA, a consequence of the limited number of possible transmission events in the data. Our approach has potential to be applied to a range of healthcare-associated infections and settings and could be applied to study the impact of other potential risk factors for transmission. Evidence generated could be used to direct infection control interventions.
Development of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus
Authors: Hong Suyeon , Ruan Shaobo , Greenberg Zachary , He Mei , McGill Jodi L. 
Published: November 2021

AbstractRespiratory syncytial virus (RSV) is one of the main pathogens associated with lower respiratory tract infections in infants and young children worldwide. Exosomes secreted by antigen presenting cells (APCs) can elicit immune responses by carrying major histocompatibility complex (MHC) class I molecules complexed with antigenic peptides and other co-stimulating factors. Therefore, we developed novel immunomagnetic nanographene particles to sequentially isolate, surface engineer, and release intact dendritic cell (DC) exosomes for use as a potential vaccine platform against RSV. The H-2Db-restricted, immunodominant peptides from RSV (M187–195 and NS161–75) were introduced to MHC-I on DC-derived exosomes to express peptide/MHC-I (pMHC-I) complexes. A mouse model of RSV infection was used to define the immunogenicity of surface engineered exosomes for activating virus-specific immune responses. Ex vivo assays demonstrated that engineered exosomes carrying RSV-specific peptides can elicit interferon-gamma (IFN-γ) production by virus-specific CD8+ T cells isolated from RSV-infected C57BL/6 mice. In vivo assays demonstrated that subcutaneous administration of both M187–195 and NS161–75 engineered exosomes to mice, with or without additional adjuvant, appeared safe and well tolerated, however, did not prime antigen-specific CD8+ T cell responses. Surface engineered exosomes are immunogenic and promising for further development as a vaccine platform.
Prediction of primary venous thromboembolism based on clinical and genetic factors within the U.K. Biobank
Authors: Kolin David A. , Kulm Scott , Elemento Olivier 
Published: November 2021

AbstractBoth clinical and genetic factors drive the risk of venous thromboembolism. However, whether clinically recorded risk factors and genetic variants can be combined into a clinically applicable predictive score remains unknown. Using Cox proportional-hazard models, we analyzed the association of risk factors with the likelihood of venous thromboembolism in U.K. Biobank, a large prospective cohort. We then created a polygenic risk score of 36 single nucleotide polymorphisms and a clinical score determined by age, sex, body mass index, previous cancer diagnosis, smoking status, and fracture in the last 5 years. Participants were at significantly increased risk of venous thromboembolism if they were at high clinical risk (subhazard ratio, 4.37 [95% CI, 3.85–4.97]) or high genetic risk (subhazard ratio, 3.02 [95% CI, 2.63–3.47]) relative to participants at low clinical or genetic risk, respectively. The combined model, consisting of clinical and genetic components, was significantly better than either the clinical or the genetic model alone (P < 0.001). Participants at high risk in the combined score had nearly an eightfold increased risk of venous thromboembolism relative to participants at low risk (subhazard ratio, 7.51 [95% CI, 6.28–8.98]). This risk score can be used to guide decisions regarding venous thromboembolism prophylaxis, although external validation is needed.
Poly(N,N-dimethylacrylamide)-coated upconverting NaYF4:Yb,Er@NaYF4:Nd core–shell nanoparticles for fluorescent labeling of carcinoma cells
Authors: Oleksa Viktoriia , Macková Hana , Engstová Hana , Patsula Vitalii , Shapoval Oleksandr , Velychkivska Nadiia , Ježek Petr , Horák Daniel 
Published: November 2021

AbstractUpconverting luminescent lanthanide-doped nanoparticles (UCNP) belong to promising new materials that absorb infrared light able to penetrate in the deep tissue level, while emitting photons in the visible or ultraviolet region, which makes them favorable for bioimaging and cell labeling. Here, we have prepared upconverting NaYF4:Yb,Er@NaYF4:Nd core–shell nanoparticles, which were coated with copolymers of N,N-dimethylacrylamide (DMA) and 2-(acryloylamino)-2-methylpropane-1-sulfonic acid (AMPS) or tert-butyl [2-(acryloylamino)ethyl]carbamate (AEC-Boc) with negative or positive charges, respectively. The copolymers were synthesized by a reversible addition-fragmentation chain transfer (RAFT) polymerization, reaching Mn ~ 11 kDa and containing ~ 5 mol% of reactive groups. All copolymers contained bisphosphonate end-groups to be firmly anchored on the surface of NaYF4:Yb,Er@NaYF4:Nd core–shell nanoparticles. To compare properties of polymer coatings, poly(ethylene glycol)-coated and neat UCNP were used as a control. UCNP with various charges were then studied as labels of carcinoma cells, including human hepatocellular carcinoma HepG2, human cervical cancer HeLa, and rat insulinoma INS-1E cells. All the particles proved to be biocompatible (nontoxic); depending on their ξ-potential, the ability to penetrate the cells differed. This ability together with the upconversion luminescence are basic prerequisites for application of particles in photodynamic therapy (PDT) of various tumors, where emission of nanoparticles in visible light range at ~ 650 nm excites photosensitizer.
No aftereffects of high current density 10 Hz and 20 Hz tACS on sensorimotor alpha and beta oscillations
Authors: Lafleur Louis-Philippe , Murray Audrey , Desforges Manon , Pacheco-Barrios Kevin , Fregni Felipe , Tremblay Sara , Saint-Amour Dave , Lepage Jean-François , Théoret Hugo 
Published: November 2021

AbstractApplication of transcranial alternating current stimulation (tACS) is thought to modulate ongoing brain oscillations in a frequency-dependent manner. However, recent studies report various and sometimes inconsistent results regarding its capacity to induce changes in cortical activity beyond the stimulation period. Here, thirty healthy volunteers participated in a randomized, cross-over, sham-controlled, double-blind study using EEG to measure the offline effects of tACS on alpha and beta power. Sham and high current density tACS (1 mA; 10 Hz and 20 Hz; 0.32 mA/cm2) were applied for 20 min over bilateral sensorimotor areas and EEG was recorded at rest before and after stimulation for 20 min. Bilateral tACS was not associated with significant changes in local alpha and beta power frequencies at stimulation sites (C3 and C4 electrodes). Overall, the present results fail to provide evidence that bilateral tACS with high current density applied over sensorimotor regions at 10 and 20 Hz reliably modulates offline brain oscillation power at the stimulation site. These results may have implications for the design and implementation of future protocols aiming to induce sustained changes in brain activity, including in clinical populations.
Effect of Au substrate and coating on the lasing characteristics of GaAs nanowires
Authors: Aman Gyanan , Mohammadi Fatemesadat , Fränzl Martin , Lysevych Mykhaylo , Tan Hark Hoe , Jagadish Chennupati , Schmitzer Heidrun , Cahay Marc , Wagner Hans Peter 
Published: November 2021

AbstractOptically pumped lasing from highly Zn-doped GaAs nanowires lying on an Au film substrate and from Au-coated nanowires has been demonstrated up to room temperature. The conically shaped GaAs nanowires were first coated with a 5 nm thick Al2O3 shell to suppress atmospheric oxidation and band-bending effects. Doping with a high Zn concentration increases both the radiative efficiency and the material gain and leads to lasing up to room temperature. A detailed analysis of the observed lasing behavior, using finite-difference time domain simulations, reveals that the lasing occurs from low loss hybrid modes with predominately photonic character combined with electric field enhancement effects. Achieving low loss lasing from NWs on an Au film and from Au coated nanowires opens new prospects for on-chip integration of nanolasers with new functionalities including electro-optical modulation, conductive shielding, and polarization control.