bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurogenesis and Proliferation of Neural Stem/Progenitor Cells Conferred by Artesunate via FOXO3a/p27Kip1 Axis in Mouse Stroke Model
Authors: Zhang Kaiyuan , Yang Yang , Ge Hongfei , Wang Ju , Lei Xuejiao , Chen Xuezhu , Wan Feng , Feng Hua , Tan Liang 
Published: November 2021

Abstract
Promoting neurogenesis and proliferation of endogenous neural stem/progenitor cells (NSPCs) is considered a promising strategy for neurorehabilitation after stroke. Our previous study revealed that a moderate dose of artesunate (ART, 150mg/kg) could enhance functional recovery in middle cerebral artery occlusion (MCAO) mice. This study aimed to investigate the effects of ART treatment on neurogenesis and proliferation of NSPCs using a rodent MCAO model. MRI results indicated that the ischemic brain volume of MCAO mice was reduced by ART treatment. The results of diffusion tensor imaging, electron microscopic, and immunofluorescence of Tuj-1 also revealed that ischemia-induced white matter lesion was alleviated by ART treatment. After ischemia/reperfusion, endogenous NSPCs were activated by ART, which was displayed by comparing the proportion of Brdu+ neuronal precursor cells in the ipsilateral subventricular zone and peri-infarct cortex. Furthermore, the neuro-restorative effects of ART were abolished by the overexpression of FOXO3a. These findings suggested that ART could rescue penumbra damage and alleviate white matter injury, subsequently contributing to post-stroke functional recovery by promoting neurogenesis and proliferation of endogenous NSPCs via the FOXO3a/p27Kip1 pathway.
Bottleneck Removal of Paclitaxel Biosynthetic Pathway By Overexpression of DBTNBT Gene Under Methyl- β- Cyclodextrin and Coronatine Elicitation in Taxus Baccata L.
Authors: Kashani Kimia , Sabet Mohammad Sadegh , Javaran Mokhtar Jalali , Moieni Ahmad 
Published: November 2021

Abstract
Paclitaxel is a highly functionalized diterpenoid that is broadly used for the treatment of several cancer types. This valuable specialized metabolite naturally exists in the inner bark of Taxus species in low amounts. The limited-scale production of paclitaxel in Taxus cell cultures has necessitated the use of several elicitors. Recently, methyl-β-cyclodextrin (CD) and coronatine (COR) have been considered to be highly effective elicitors in producing plant specialized metabolites. Given the limited production of paclitaxel due to the rate limiting enzymes' function, bottleneck removal is conducive to the production of more significant amounts of paclitaxel. In the present study, the full length of DBTNBT coding sequence (CDS), as one of the paclitaxel pathway bottlenecks, was integrated downstream of the CaMV 35S promoter (pCAMBIA1304-DBTNBT) and transiently expressed in Taxus baccata leaves via Agrobacterium tumefaciens and vacuum infiltration method. Paclitaxel production and the expression level of several involved genes were evaluated through different treatments. The transient overexpression of the DBTNBT gene, associated with dual elicitation, resulted in 7.4-fold more paclitaxel production compared with the no-inoculation/no-elicitation control. These ratios were 2.1 and 1.8 in the CD+COR and pCAM treatments, respectively. Among T13αH, T14βH, DBAT, BAPT, DBTNBT, and ABC genes, the most increased expression level belonged to the DBTNBT gene, followed by ABC and BAPT genes. It seems as though in the near future, bottleneck removal could be used on a large scale in Taxus metabolic engineering, resulting in the relative removal of some other bottlenecks and an increase in the final paclitaxel production.
Radiomic Analysis for Predicting Prognosis of Colorectal Cancer From Preoperative 18F-FDG PET/CT
Authors: Lv Lilang , Xin Bowen , Hao Yichao , Yang Ziyi , Xu Junyan , Wang Lisheng , Wang Xiuying , Song Shaoli , Guo Xiaomao 
Published: November 2021

Abstract
Background To develop and validate a survival model with clinico-biological features and 18F- FDG PET/CT radiomic features via machine learning, and for predicting the prognosis from the primary tumor of colorectal cancer.Methods A total of 196 pathologically confirmed colorectal cancer patients (stage I to stage IV) were included. Preoperative clinical factors, serum tumor markers, and PET/CT radiomic features were included for the recurrence-free survival analysis. For the modeling and validation, patients were randomly divided into the training (n=137) and validation (n=59) set, while the 78 stage III patients [training (n=55), and validation (n=23)] was divided for the further experiment. After selecting features by the log-rank test and variable-hunting methods, random survival forest (RSF) models were built on the training set to analyze the prognostic value of selected features. The performance of models was measured by C-index and was tested on the validation set with bootstrapping. Feature importance and the Pearson correlation were also analyzed. Results Radiomics signature with four PET/CT features and four clinical factors achieved the best result for prognostic prediction of 196 patients (C-index 0.780, 95% CI 0.634 - 0.877). Moreover, four features (including two clinical features and two radiomics features) were selected in the 78 stage III patients (C-index was 0.820, 95% CI 0.676-0.900). K-M curves of both models significantly stratified low-risk and high-risk groups (P < 0.0001). Pearson correlation analysis demonstrated that selected radiomics features were correlated with tumor metabolic factors, such as SUVmean, SUVmax.Conclusion This study presents integrated clinico-biological-radiological models that can accurately predict the prognosis from the preoperative 18F-FDG PET/CT radiomics in colorectal cancer. It is of potential value in assisting the management and decision making for precision treatment in colorectal cancer.Trial registration The retrospectively registered study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (No. 1909207-14-1910) and the data were analyzed anonymously.
How do maternal emotion and sleep conditions affect infant sleep: a prospective cohort study
Authors: Lin Xuemei , Zai Ronghui , Mo Jiafeng , Sun Jingzhou , Chen Peishan , Huang Yuejun 
Published: November 2021

Abstract
Background: Recent studies suggest that the incidence of infant sleep disorder is related to maternal emotional and sleep conditions, but how they influence each other is not fully understood. Methods: A total of 513 pairs of parents and infants were enrolled in this prospective cohort study. Maternal emotional and sleep conditions were assessed using a self-rating depression scale, self-rating anxiety scale, and Pittsburgh Sleep Quality Index at the third trimester and within 3 months after delivery. Infant sleep was assessed by the Brief Screening Questionnaire for Infant Sleep Problems within 3 months after birth. Expression of the glucocorticoid receptor (GR), melatonin receptors (MR), exchange proteins directly activated by cAMP (EPAC) receptors, and dopamine receptor (DR) in the placenta was detected by immunohistochemistry. Methylation of the promoter regions for the GR (NR3C1 and NR3C2), MR (MTNR1A and MTNR1B), EPAC (RASGRF1 and RASGRF2), and DR (DRD1 and DRD2) genes was assessed by next generation sequencing-based bisulfite sequencing PCR. Results: The incidence of sleep disorders in infants 0-3 months of age in this cohort was 40.5%. Risk factors for infant sleep disorder were low education level of the father, maternal postpartum depression, postpartum anxiety, postpartum sleep disorder, and maternal sleep disorder extend from the third trimester to postpartum. There was no difference in expression of placental DR, GR, MR, and EPAC between mothers whose infants were with and without sleep disorders. Methylation of MTNR1B was higher and expression of MR was lower in the placenta of mothers with sleep disorder in the third trimester than in mothers without sleep disorder. Level of NR3C2 methylation was lower and GR expression was higher in the placenta of mothers with sleep disorder extend from the third trimester to postpartum than in mothers without sleep disorder. Conclusion: Maternal sleep disorders in the third trimester could lead to decreased expression of MR by up-regulating MTNR1B methylation, and then resulting in elevated cortisol levels and increased GR expression by down-regulating NR3C2 methylation, which could increase the incidence of maternal postpartum sleep disorders, finally, the maternal postpartum sleep disorder could result in the high incidence of infant sleep disorder.
Transcriptome analysis revealed growth phase-associated changes of a centenarian-originated probiotic Bifidobacterium animalis subsp. lactis A6
Authors: Wang Hui , An Jieran , Fan Chengfei , Zhai Zhengyuan , Zhang Hongxing , Hao Yanling 
Published: November 2021

Abstract
Background
The physiology and application characteristics of probiotics are closely associated with the growth phase. Bifidobacterium animalis subsp. lactis A6 is a promising probiotic strain isolated from the feces of a healthy centenarian in China. In this study, RNA-seq was carried out to investigate the metabolic mechanism between the exponential and the stationary phase in B. lactis A6.
Results
Differential expression analysis showed that a total of 810 genes were significantly changed in the stationary phase compared to the exponential phase, which consisted of 392 up-regulated and 418 down-regulated genes. The results showed that the transport and metabolism of cellobiose, xylooligosaccharides and raffinose were enhanced at the stationary phase, which expanded carbon source utilizing profile to confront with glucose consumption. Meanwhile, genes involved in NH3 production were up-regulated at the stationary phase to enhance acid tolerance during fermentation. In addition, peptidoglycan biosynthesis was significantly repressed, which is comparable with the decreased growth rate during the stationary phase. Remarkably, a putative gene cluster encoding Tad pili was up-regulated 6.5~12.1-fold, which is consistent with the significantly increased adhesion rate to mucin from 2.38–4.90% during the transition from the exponential phase to the stationary phase.
Conclusions
This study reported growth phase-associated changes of B. lactis A6 during fermentation, including expanded carbon source utilizing profile, enhanced acid tolerance, and up-regulated Tad pili gene cluster responsible for bacterial adhesion in the stationary phase. These findings provide a novel insight into the growth phase associated characteristics in B. lactis A6 and provide valuable information for further application in the food industry.
A Qualitative Dual-Site Analysis of The Pharmacist Discharge Care (PHARM-DC) Intervention Using The CFIR Framework
Authors: Murry Logan Thomas , Kennelty Korey , Keller Michelle , Pevnick Joshua , Schnipper Jeffrey 
Published: November 2021

Abstract
Introduction: Older adults face several challenges when transitioning from acute hospitals to community-based care. The PHARMacist Discharge Care (PHARM-DC) intervention is a pharmacist-led Transitions of Care (TOC) program intended to reduce 30-day hospital readmissions and emergency department visits at two large hospitals. This study used the Consolidated Framework for Implementation Research (CFIR) framework to evaluate pharmacist perceptions of the PHARM-DC intervention.Methods: Intervention pharmacists and pharmacy administrators were purposively recruited by study team members located within each participating institution. Study team members located within each institution coordinated with two study authors unaffiliated with the institutions implementing the intervention to conduct interviews and focus groups remotely via telecommunication software. Interviews were recorded and transcribed, with transcriptions imported into NVivo for qualitative analysis. Qualitative analysis was performed using an iterative process to identify “a priori” constructs based on CFIR domains (intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation) and to create overarching themes as identified during coding.Results: In total, ten semi-structured interviews and one focus group were completed across both hospitals. At Site A, six interviews were conducted with intervention pharmacists and pharmacists in administrative roles. Also at Site A, one focus group comprised of five intervention pharmacists was conducted. At Site B, interviews were conducted with four intervention pharmacists and pharmacists in administrative roles. Three overarching themes were identified: PHARM-DC and Institutional Context, Importance of PHARM-DC Adaptability, and Recommendations for PHARM-DC Improvement and Sustainability. Increasing pharmacist support for technical tasks and navigating pharmacist-patient language barriers were important to intervention implementation and delivery. Identifying cost-savings and quantifying outcomes as a result of the intervention were particularly important when considering how to sustain and expand the PHARM-DC intervention.Conclusion: The PHARM-DC intervention can successfully be implemented at two institutions with considerable variations in TOC initiatives, resources, and staffing. Future implementation of PHARM-DC interventions should consider the themes identified, including an examination of institution-specific contextual factors such as the roles that pharmacy technicians may play in TOC interventions, the importance of intervention adaptability to account for patient needs and institutional resources, and pharmacist recommendations for intervention improvement and sustainability.
Transscleral vs Endoscopic Cyclophotocoagulation: Safety and Efficacy When Combined with Phacoemulsification
Authors: Nirappel Abraham , Klug Emma , Neeson Cameron , Chachanidze Mari , Hall Nathan , Chang Ta , Shen Lucy , Valle David Sola-Del 
Published: November 2021

Abstract
Precis: Phacoemulsification combined with MicroPulse transscleral cyclophotocoagulation appears to provide significantly greater long-term IOP reduction than phacoemulsification combined with endoscopic cyclophotocoagulation without compromising safety.Purpose: To compare the effectiveness and safety of phacoemulsification combined with endoscopic cyclophotocoagulation (phaco/ECP), phacoemulsification combined with MicroPulse transscleral cyclophotocoagulation (phaco/MP-TSCPC), and phacoemulsification alone (phaco) in the treatment of coexisting cataract and glaucoma. Methods: Retrospective cohort study of consecutive cases at Massachusetts Eye & Ear. The main outcome measures were the cumulative probabilities of failure between the phaco/ECP group, phaco/MP-TSCPC group, and the phaco alone group with failure defined as reaching NLP vision at any point postoperatively or the inability to maintain ≥20% IOP reduction from baseline with IOP between 5-18 mmHg. Additional outcome measures included changes in average IOP, number of glaucoma medications, and complication rates. Results: 64 eyes from 64 patients (25 phaco/ ECP, 20 phaco/ MPTSCPC, 19 phaco alone) were included in this study. The groups did not differ in age (mean 71.04 ± 6.7 years) or length of follow-up time. Primary open-angle glaucoma was the most common type of glaucoma in the phaco alone (42%) and phaco/ECP (48%) groups while mixed-mechanism glaucoma was the most common type in the phaco/MP-TSCPC group (40%). The mean IOP reductions at 1 year were 3.07 ± 5.3 mmHg from a baseline of 15.78 ± 4.7 in the phaco/ECP group, 6.0 ± 4.3 mmHg from a baseline of 18.37 ± 4.6 in the phaco/MP-TSCPC group and 1.0 ± 1.6 from a baseline of 14.30 ± 4.2 mmHg in the phaco alone group. Surgical failure was less likely in eyes in the phaco/MP-TSCPC and phaco/ECP groups compared to phaco alone based on the Kaplan-Meier survival criteria, with failure defined as the inability to maintain an IOP reduction of 20% or more with IOP between 5-18 mm Hg long term. There were no differences in complications among the three groups. Conclusions: Phaco/MP-TSCPC appears to provide for greater long-term IOP control than phaco alone and phaco/ECP. All three procedures had similar safety profiles.
Multi-State MRAM Cells For Hardware Neuromorphic Computing
Authors: Rzeszut Piotr , Chęciński Jakub , Brzozowski Ireneusz , Ziętek Sławomir , Skowroński Witold , Stobiecki Tomasz 
Published: November 2021

Abstract
Magnetic tunnel junctions (MTJ) have been successfully applied in various sensing application and digital information storage technologies. Currently, a number of new potential applications of MTJs are being actively studied, including high-frequency electronics, energy harvesting or random number generators. Recently, MTJs have been also proposed in designs of new platforms for unconventional or bio-inspired computing. In the present work, it is shown that serially connected MTJs forming a multi-state memory cell can be used in a hardware implementation of a neural computing device. The main purpose of the multi-cell is the formation of quantized weights in the network, which can be programmed using the proposed electronic circuit. Multi-cells are connected to a CMOS-based summing amplifier and a sigmoid function generator, forming an artificial neuron. The operation of the designed network is tested using a recognition of hand-written digits in 20 × 20 pixels matrix and shows detection ratio comparable to the software algorithm, using weights stored in a multi-cell consisting of four MTJs or more.
SARS-CoV-2 infects human GnRH neurons and tanycytes, disrupting hypothalamic-pituitary hormonal axes
Authors: Sauve Florent , Nampoothiri Sreekala , Fernandois Daniela , Coelho Caio , Dam Julie , Ternier Gaëtan , Cotellessa Ludovica , Iglesias Cristina , Müller-Fielitz Helge , Dewisme Julie , Cecon Erika , Lebouvier Thibaud , Perbet Romain , Florent Vincent , Baroncini Marc , Sharif Ariane , Ereño-Orbea June , Mercado-Gomez Maria , Palazon Asis , Mattot Virginie , Pasquier Florence , Catteau-Jonard Sophie , Jockers Ralf , Storme Laurent , Hrabovszky Erik , Trottein François , Martínez-Chantar María , Nogueiras Ruben , Schwaninger Markus , Pigny Pascal , Poissy Julien , Chachlaki Konstantina , Maurage Claude-Alain , Giacobini Paolo , Rasika S , Prevot Vincent 
Published: November 2021

Abstract
Neuroinvasion by SARS-CoV-2 is now accepted. To investigate whether low testosterone levels observed in men with severe COVID-19 could be of central origin, we retrospectively analyzed blood samples from 60 male intensive-care patients and explored SARS-CoV-2 brain entry using animal and cellular models as well as adult COVID-19 patient and fetal human brains. Most hypotestosteronemic patients displayed hypogonadotropic hypogonadism or abnormal hypothalamic-pituitary-gonadal axis regulation. Neurons producing gonadotropin-releasing hormone (GnRH), the master molecule controlling fertility, expressed angiotensin-converting enzyme 2 and neuropilin-1, two host-cell factors mediating infection, and were infected and dying in all COVID-19 patient brains. Tanycytes - hypothalamic glia that regulate GnRH secretion - were also infected. Additionally, human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, richly expressed both the above host-cell susceptibility factors and formyl peptide receptor 2, a putative vomeronasal receptor that also appeared involved in SARS-CoV-2 pathogenesis in humans and mice. Finally, a fetal human GnRH cell line expressing all these receptors could be infected by a SARS-CoV-2-like pseudovirus. Together, our findings suggest that GnRH neurons, which may be implicated in brain development and aging in addition to reproduction, are particularly vulnerable to SARS-CoV-2 in both adults and fetuses/newborns, with potentially devastating long-term consequences.
Indoor Air Pollution Effects On Pediatric Asthma Are Submicron Aerosol Particles Dependent
Authors: Juskiene Izabele , Prokopciuk Nina , Franck Ulrich , Valiulis Algirdas , Valskys Vaidotas , Mesceriakova Vitalija , Kvedariene Violeta , Valiulyte Indre , Poluzioroviene Edita , Sauliene Ingrida , Valiulis Arunas 
Published: November 2021

Abstract
The school environment is crucial for the child’s health and wellbeing. On the other hand, the data about the role of school’s aerosol pollution on the etiology of chronic non-communicable diseases remain scarce.Objectives: To evaluate the level of indoor aerosol pollution in primary schools and its relation to the incidence of doctor’s diagnosed asthma among younger school-age children.Methods: The cross-sectional study was carried out in 11 primary schools of Vilnius during one year of education from autumn 2017 to spring 2018. Particle number (PNC) and mass (PMC) concentrations in the size range of 0.3-10 µm were measured using an Optical Particle Sizer (OPS, TSI model 3330). The annual incidence of doctor’s diagnosed asthma in each school was calculated retrospectively from the data of medical records.Results: The total number of 6-11 years old children participated in the study was 3638. The incidence of asthma per school ranged from 1.8 to 6.0%. Mean indoor air pollution based on measurements in classrooms during the lessons was calculated for each school. Levels of PNC and PMC in schools ranged between 33.0-168.0 part/cm 3 and 1.7-6.8 µg/m 3 , respectively. There was a statistically significant correlation between the incidence of asthma and PNC as well as asthma and PMC in the particle size range of 0.3-1 µm (r=0.66, p=0.028) and (r=0.71, p=0.017) respectively. No significant correlation was found between asthma incidence and indoor air pollution in the particle size range of 0.3-2.5 and 0.3-10 µm.Conclusions: We concluded that the number and mass concentrations of indoor air aerosol pollution in primary schools in the particle size range of 0.3-1 μm are primarily associated with the incidence of doctor’s diagnosed asthma among younger school age-children.
Symbiont-driven niche expansion shaped the adaptive radiation of insects
Authors: Cornwallis Charlie , Padje Anouk van't , Ellers Jacintha , Klein Malin , Jackson Raphaella , Kiers Toby , West Stuart , Henry Lee 
Published: November 2021

Abstract
For over 300 million years, insects have relied on symbiotic microbes for nutrition and defence1,2. However, it is unclear whether specific ecological conditions have repeatedly favoured the evolution of symbioses, and how this has influenced insect diversification1,3,4. Using data on 1844 microbe-insect symbioses across 400 insect families, we found that symbionts have allowed insects to radiate into a range of feeding niches deficient in B vitamins, including phloem, blood and wood. In some cases, such as herbivorous insects, the shift to a new niche has resulted in spectacular species proliferation. In other niches, such as strict blood feeding, diversification has been severely constrained. Symbioses therefore appear to solve universal nutrient deficiencies for insects, but the consequences for insect diversification depend on the feeding niche invaded.