bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-Time Decision-Making on Whether to Incorporate Neurorehabilitation Technology: Informing Developers on a Day in the Life of a Therapist
Authors: Celian Courtney , Swanson Veronica , Shah Maahi , Newman Caitlin , Fowler-King Bridget , Gallik Sarah , Reilly Kaitlin , Reinkensmeyer David J. , Patton James , Rafferty Miriam R. 
Published: May 2021

Abstract
Background
Neurorehabilitation engineering faces numerous challenges to translating new technologies, but it is unclear which of these challenges are most limiting. Here we focus on tracing the real-time behavior and rehabilitation technology (RT) use decisions of the primary gatekeepers of RT: rehabilitation therapists.
Methods
Three OTs and two PTs employed at a major, technology-encouraging rehabilitation hospital wrote vignettes from a written prompt describing their RT use decisions during treatment sessions with nine patients (4 with stroke, 2 traumatic brain injury, 1 spinal cord injury, 1 with multiple sclerosis). We then coded the vignettes using deductive qualitative analysis from 17 constructs derived from the RT literature and the Consolidated Framework for Implementation Research (CFIR) to analyze the vignettes. Data were synthesized using summative content analysis.
Results
Of the constructs recorded, the five most prominent are from CFIR determinants of: (i) relative advantage, (ii) personal attributes of the patients, (iii) clinician knowledge and beliefs of the device/intervention, (iv) complexity of the devices including time and setup, and (v) organizational readiness to implement. Therapists characterized candidate RT as having a relative disadvantage compared to conventional treatment due to lack of relevance to functional training. RT design also often failed to take into account the multi-faceted personal attributes of the patients, including diagnoses, goals, and physical and cognitive limitations. Clinicians’ comfort with RT was increased by their previous training but was decreased by the perceived complexity of RT. Finally, therapists have limited time to gather, setup, and use RT.
Conclusions
Despite decades of design work aimed at creating clinically useful RT, many lack compatibility with clinical translation needs in inpatient neurologic rehabilitation. New RT continue to impede the immediacy, versatility, and functionality of hands-on therapy mediated treatment with simple everyday objects.
A novel machine learning-based approach for the computational functional assessment of pharmacogenomic variants
Authors: Pandi Maria-Theodora , Koromina Maria , Tsafaridis Iordanis , Patsilinakos Sotirios , Christoforou Evangelos , Spek Peter J van der , Patrinos George P 
Published: May 2021

Abstract
Background: The field of pharmacogenomics focuses on the way a person’s genome affects his or her response to a certain dose of a specified medication. The main aim is to utilize this information to guide and personalize the treatment in a way that maximizes the clinical benefits and minimizes the risks for the patients, thus fulfilling the promises of personalized medicine. Technological advances in genome sequencing, combined with the development of improved computational methods for the efficient analysis of the huge amount of generated data, have allowed the fast and inexpensive sequencing of a patient’s genome, hence rendering its incorporation into clinical routine practice a realistic possibility. Results: The potential availability of a vast number of identified genetic variants in a clinical setting highlights the necessity of developing a method to evaluate and prioritize this information towards its exploitation in guiding medication or dosing scheme systematically and effectively. In this direction, the present study examines the development of a computational model that can classify new variants according to their possible effects on protein function, which in turn affects drug response, by using as a training set a dataset of functionally validated single nucleotide variants (SNVs) located in pharmacogenes. Conclusion: Overall, the proposed model holds promise to lead to an extremely useful variant prioritization and scoring tool with interesting clinical applications in pharmacogenomics.
Probability of the Alzheimer’s disease based on common and rare genetic variants
Authors: Escott-Price Valentina , Schmidt Karl Michael 
Published: May 2021

Abstract
Background: Alzheimer’s disease, among other neurodegenerative disorders, spans decades in individuals’ life and exhibits complex progression, symptoms and pathophysiology. Early diagnosis is essential for disease prevention and therapeutic intervention. Genetics may help identify individuals at high risk. As thousands of genetic variants may contribute to the genetic risk of Alzheimer’s disease, the polygenic risk score (PRS) approach has been shown to be useful for disease risk prediction. The APOE- ε4 allele is a known common variant associated with high risk to AD, but also associated with earlier onset. Rare variants usually have higher effect sizes than common ones; their impact may not be well captured by the PRS. Instead of standardised PRS, we propose to calculate the disease probability as a measure of disease risk that allows comparison between individuals. Methods: We estimate AD risk as a probability based on PRS and separately accounting for APOE, AD rare variants and the disease prevalence in age groups. The mathematical framework makes use of genetic variants effect sizes from summary statistics and AD disease prevalence in age groups. Results: The AD probability varies with respect to age, APOE status and presence of rare variants. In age group 65+ the probability of AD grows from 0.03 to 0.18 (without APOE), and 0.07 to 0.7 (APOE e4e4 carriers) as PRS increases. In 85+, these values are 0.08-0.6 and 0.3-0.85. Presence of rare mutations, e.g. in TREM2, may increase the probability (in 65+) from 0.02 at the negative tail of the PRS to 0.3.Conclusions: Our approach accounts for the varying disease prevalence in different genotype and age groups when modelling the APOE and rare genetic variants risk in addition to PRS. This approach can be directly implemented in a clinical setting and easily updated for novel rare variants and for other populations when appropriate ethnic GWASes appear.
Effect of HMG on Pregnancy Outcomes in Patients undergoing IUI Cycle -An Analysis of 1230 IUI Cycles
Authors: Ou Miaoxian , Lin Han , Xu Pei , Ma Kaichi , Liu Mingxing 
Published: May 2021

Abstract
Background: This aim of this study was to evaluate the effect of human menopause gonadotropin (HMG) on pregnancy outcomes of infertility patients with intrauterine insemination (IUI) treatments.Methods: This retrospective cohort study analyzed couples using 75 IU HMG as initiate ovarian stimulation method for IUI from January 2015 to December 2019. Couples were divided into four groups according to a total dose of HMG: 189 cycles with a dose <500 IU, 601 with a dose 500 to1000 IU, 199 with a dose 1000 to 1500 IU and 241 with a dose ＞1500 IU. The differences in baseline characteristics and pregnancy outcomes including among the four groups were investigated. We used a logistic regression model to further study the association between various doses of HMG and pregnancy outcomes and adjusted for confounding factors.Results: The study included 792 couples with 1230 cycles, and pregnancy was achieved in 212 (17.2%) cycles, while live birth was achieved in 176 (14.3%) cycles. Stratified analyses revealed that a higher dose of HMG was associated with increased pregnancy rate (PR), live birth rate (LBR), endometrial thickness (EMT) on insemination day, number of follicle ≥18 mm, serum estrogen 2( E2) level, and EMT on the trigger day among four groups, which were all statistically different (P＜0.05). The logistic regression indicated that both PR and LBR were positively associated with the total dose and day of HMG, which were statistically different (P＜0.05).Conclusion: Increasing the total dose and day of HMG may benefit the serum E2 level, EMT, follicle development, and pregnancy outcomes in 75IU HMG stimulated IUI cycles.
Circulating levels of asprosin and its association with insulin resistance and renal function in type2 diabetes mellitus and diabetic nephropathy patients
Authors: Goodarzi Golnoosh , Setayesh Leila , Fadaei Reza , Khamseh Mohammad Ebrahim , Aliakbari Fereshteh , Hosseini Jalil , Moradi Nariman 
Published: May 2021

Abstract
Introduction
: Adipokines have an important role in development and progression of type 2 diabetes mellitus (T2DM) and its complications such as nephropathy. Asprosin is a recently discovered adipokine that involve in glucose metabolism and inflammation process. The present study sought to evaluate asprosin levels in patients with T2DM and T2DM + nephropathy (NP) compared to controls and its relation with markers of insulin resistance, inflammation and renal function.
Methods
Serum levels of asprosin, adiponectin, IL-6 and TNF-α were measured in 55 control, 54 T2DM and 55 T2DM + NP patients using ELISA kits.
Results
Asprosin was found to be higher in T2DM (6.73 ± 1.67) and T2DM + NP (7.11 ± 1.54) compared to controls (4.81 ± 1.09) (p < 0.001), while adiponectin indicated a lower concentration in both patient groups compared with controls. Moreover, IL-6 and TNF-α indicated higher levels in both patients group compared with controls. Asprosin indicated a positive correlation with HbA1c, FBG, TC, LDL-C, IL-6 and TNF-α in T2DM group. In the patients with T2DM + NP asprosin positively correlated with BMI, HbA1c, insulin, HOMA-IR, Cr, UAE, IL-6 and TNF-α and inversely correlated with eGFR.
Conclusion
Higher concentration of asprosin in T2DM and T2DM + NP and its relation with glucose and lipid metabolism, and markers of renal function and inflammation suggested a possible role for this adipokine in the pathogenesis of T2DM and nephropathy.
Autoantibody of Interleukin-17A Induced by Recombinant Mycobacterium Smegmatis Attenuates Airway Inflammation in Neutrophilic Asthma
Authors: Chen Ling , Xu Wanting , Mao Song , Zhu Ruochen , Zhang Jianhua 
Published: May 2021

Abstract
Asthma is a chronic inflammatory disorder, previous studies have shown Interleukin (IL)-17A is an important contributor to the development of severe asthma characterized by intense neutrophilic inflammation and less responsive to corticosteroid. Hence, IL-17A-neutrophil axis may be a potential therapeutic target for asthma. In our previous work, we constructed a recombinant Mycobacterium smegmatis expressing fusion protein Ag85A-IL-17A (rMS) and confirmed that it could induce the production of IL-17A autoantibody in vivo. Here, in the present study, we aim to further investigate the effects of the rMS on airway inflammation and explore the underlying mechanisms in a murine model of neutrophilic asthma. The murine model of neutrophilic asthma was established with ovalbumin (OVA), and mice were intranasally vaccinated with rMS, then IL-17A autoantibody in sera was detected, and its anti-inflammatory effects on inflammatory cell infiltration and expression of inflammatory mediators involved in IL-17A-neutrophil axis in bronchoalveolar lavage fluid (BALF) as well as histopathological changes of lung tissues were evaluated. The data showed that sustained high-titer of IL-17A autoantibody was detected in rMS group, intranasal vaccination significantly decreased inflammatory cells, cytokines and chemokines related to IL-17A-neutrophil axis in BALF, suppressed the activity of neutrophil enzyme, and histological analysis manifested the rMS remarkably reduced inflammatory cell infiltration, mucus secretion and airway epithelial thickness. Overall, these results demonstrate the rMS ameliorated airway inflammation in mice with neutrophilic asthma via inducing IL-17A autoantibody and regulating the IL-17A-neutrophil axis, thus providing a possible novel treatment in neutrophilic asthma.
Evaluating Polymers Interplay to Investigate Lignocellulose Recalcitrance
Authors: Leroy Amandine , Falourd Xavier , Foucat Loïc , Méchin Valérie , Guillon Fabienne , Paës Gabriel 
Published: May 2021

Abstract
Background : Biomass recalcitrance is governed by various molecular and structural factors but there is still a lack of understanding on the interplay between these multiscale factors. In this study, hot water pretreatment (HWP) was applied to maize stem internode in order to highlight the impact of polymer interactions and their ultrastructure on the accessibility and recalcitrance of the lignocellulosic biomass. The impact of HWP were analysed at different scales, from the polymers ultrastructure or water mobility to the cell wall organization by combining complementary compositional, spectral and NMR analysis. Result : HWP increased the kinetics and yield of saccharification. The chemical characterization showed that HWP altered cell wall composition with a loss of hemicelluloses (up to 45% for HWP 40 min) and of ferulic acid cross-linking, associated with a lignin enrichment. The lignin structure was also altered (up to 35% decrease of β-O-4 bonds), associated to a slight depolymerization/repolymerization depending on the treatment time. The increase of the T 1 ρ H , T HH and specific surface area (SSA) showed that the cellulose environment was looser after pretreatment. These changes were related to an increase of the accessibility of more constrained water to the cellulose across 5–15 nm pore size range. Conclusion : The loss of hemicelluloses and changes in polymers structural features induced by HWP leads to reorganization of the lignocellulosic matrix. These modifications led to an increase in the SSA and a water redistribution allowing an increase in the accessibility of cellulases and an enhancement of the hydrolysis. Interestingly, the lignin content had no negative effect on the enzymatic hydrolysis but a higher lignin condensed state seemed to promote saccharification. The environment and organization of lignin is thus more important to consider than its concentration to explain cellulose accessibility. Elucidating the interactions between polymers is the key to understanding LB recalcitrance and to find the best severity conditions to optimise HWP in sustainable biorefineries.
Strata and Surface Influence Range of Deep Coal Mining for Mine Land Reuse
Authors: Li Huaizhan , Guo Kaikai , Guo Guang-li 
Published: May 2021

Abstract
The rational assessment and determination of strata and surface influence range of underground coal mining is straightly associated to the safe production of the wellbore, the reuse of mine land and the regional development. With the depth of coal mining in the world increasing, if the boundary curve of strata and surface movement continues to be considered as a straight line, there will be a great deviation from the real situation, which will seriously waste the land resources of mining area. To solve this issue, the numerical simulation methods were employed to investigate the stratum and surface movement boundary curves of deep caving and backfilling mining in this paper. The findings indicated that: 1) The strata and surface movement boundary of deep caving and backfilling mining were all curves, and they were in accordance with the exponential function, but the influence range of strata and surface movement of deep different mining methods were different; 2) The backfilling rate of deep backfilling mining had an influence on movement boundary of strata and surface. With the backfilling rate decreasing, the influence range of strata and surface movement boundary were increased. 3) The research results were applied to a case in order to confirm the new methods for determining the influence range of strata and surface movement of deep mining. Example application shows that the safe production of the wellbore not only can be guaranteed, but also the reuse area of the mine field can be enhanced.
ZIP7 Maintains Colon Cancer Radioresistance by Regulating Zinc-dependent Epithelial-mesenchymal Transition
Authors: Zhang Qinglin , Nie He , Sun Jing , Pan Jiadong , qiang zhan 
Published: May 2021

Abstract
Background: Irradiation-induced radioresistance often leads to the therapeutic failure of colon cancer. By regulating the redistribution of intracellular zinc, ZIP7 plays a dominating role in the activation of many critical signaling pathways in the progression of tumors. However, the relationship between ZIP7 and radioresistance is still unclear. Methods: ZIP7 expression of colon cancer was evaluated by analyzing public data from the GEPIA and CPTAC databases and validated based on immunohistochemistry (IHC) staining. Clonogenic survival assay was employed to examine the influence of intracellular zinc interference and ZIP7 knockdown on radioresistance of colon cancer, based on radioresistant colon cancer cells. At last, Western blot was performed to preliminarily explore the potential mechanisms. Results: ZIP7 was significantly upregulated in human colon cancers compared with adjacent normal tissues. ZIP7 knockdown could significantly reduce the radioresistance of colon cancer cells, while transmembrane ionophore of zinc could partially reverse this effect. In terms of mechanisms, ZIP7 knockdown significantly reversed the radiation-induced expression of elevated ZEB1 and down-regulated E-cadherin through regulating zinc. Conclusion: ZIP7 is crucial to maintain radioresistance of colon cancer cells through regulation of zinc distribution, and at least partially by maintenance of epithelial-mesenchymal transition (EMT).
Characteristics and recognition of guardians living in the urgent protective action planning zone of the Genkai Nuclear Power Plant, Saga Prefecture, Japan who wished to receive pre-distribution stable iodine for their children
Authors: Matsunaga Hitomi , Orita Makiko , Taira Yasuyuki , Takamura Noboru 
Published: May 2021

Abstract
Purpose：The aim of this study was to clarify the characteristics and the awareness of nuclear prevention measures including prophylactic stable iodine (SI) of guardians of 0- to 6-year-old children living in the urgent protective action planning zone (UPZ) of the Genkai Nuclear Power Plant (GNPP), Japan. Methods：Of these 1172 guardians, 973 responded that they wished to receive pre-distribution of stable iodine (PDSI) and 199 did not wish to receive PDSI. Results: Logistic regression analysis showed that the following items were independently associated with guardians who wished to receive PDSI for their children: thinking that pregnant women should take prophylactic SI (odds ratio [OR]=6.57, 95% confidence interval [CI]: 4.62–9.35; p<0.01); wishing to participate in a lecture about the health effects of radiation exposure (OR=1.99, 95%CI: 1.40–2.82; p<0.01); thinking that SI can prevent exposure from all radionuclides (OR=1.93, 95%CI: 1.24–2.99; p<0.01); awareness of SI before the study (OR=1.91, 95%CI: 1.35–3.00; p<0.01); and anxiety about prophylactic SI for their children (OR=0.33, 95%CI: 0.20–0.55; p<0.01). The GNPP was one of the nuclear power plants in Japan that resumed operations after the Fukushima Dai-ichi Nuclear Power Plant accident in 2011. Conclusion: These results suggest that some residents have incomplete knowledge about nuclear prevention, including SI. Therefore, it is essential to educate residents and communicate the health risks of radiation exposure with residents living around nuclear power plants. Furthermore, it is important to train specialists to educate and communicate with residents to prepare for a nuclear accident.
Human Umbilical Cord Mesenchymal Stem Cell (HUCMSC)-derived Exosomes as a Cell-Free Therapy for Soluble Fms-like Tyrosine Kinase-1 (Sflt-1)-induced Endothelial Dysfunction in Preeclampsia
Authors: CHANG XINWEN , HE QIZHI , WANG MINGMIN , JIA LINYAN , DUAN TAO , WANG KAI 
Published: May 2021

Abstract
BackgroundPreeclampsia is a unique multisystem disorder that affects 5-8% of pregnancies. A high level of soluble fms-like tyrosine kinase-1 (sFlt-1) is a hallmark of preeclampsia that causes endothelial dysfunction. Exosomes derived from mesenchymal stem cells (MSCs) have been indicated to improve endothelial performances by transporting signals to target cells. We hypothesized that exosomes derived from MSCs have potential effects against preeclampsia. MethodsWe collected human umbilical cord MSC-derived exosomes (HUCMSC-exos) by ultracentrifugation. The size and morphology of the exosomes were examined using a transmission electron microscope and nanoparticle tracking analysis. Pregnant mice were injected with murine sFlt-1 adenovirus to build the preeclampsia-like mouse model and then treated with HUCMSC-exos. Human umbilical vein endothelial cells (HUVECs) were infected with lentiviruses expressing tet-on-sFlt-1 to obtain cells overexpressing sFlt-1. Cell proliferation and migration assays were used to measure the endothelial functions. The exosomes enriched proteins underlying mechanisms were explored by proteomic analysis.ResultsIn the current study, we successfully collected the cup-shaped HUCMSC-exos with diameters of 30-150 nm. In the sFlt-1-induced preeclampsia mouse model, HUCMSC-exos exhibited beneficial effects on adverse birth events by decreasing blood pressure and improving fetal birth weight. In addition, preeclamptic dams that were injected with HUCMSC-exos had rebuilt dense placental vascular networks. Furthermore, we observed that HUCMSC-exos partially rescued sFlt-1-induced HUVECs dysfunction in vitro. Proteomics analysis of HUCMSC-exos displayed functional enrichment in biological processes related to vesicle-mediated transport, cell communication, cell migration, and angiogenesis.ConclusionWe propose that exosomes derived from HUCMSCs play beneficial roles in the birth outcomes of sFlt-1-induced preeclamptic mice by promoting angiogenesis.
Low-level overexpression of wild type TDP-43 causes late-onset, progressive neurodegeneration and paralysis in mice
Authors: Yang Chunxing , Qiao Tao , Yu Jia , Wang Hongyan , Guo Yangsu , Salameh Johnny , Metterville Jake , Parsi Sepideh , Brown Robert H. , Cai Huaibin , Xu Zuoshang 
Published: May 2021

Abstract
Background: Modestly elevated levels of transactive response DNA binding protein (TDP-43) gene have been reported in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neuromuscular diseases. However, whether this modest elevation triggers neurodegeneration is not known. Although high levels of TDP-43 overexpression have been modeled in mice and shown to cause early death, models with low-level overexpression that mimic the human condition have not been established. In this study, we tried to fill this knowledge gap.Methods: Transgenic mice overexpressing wild type TDP-43 at less than 60% above the endogenous CNS levels were constructed, and their phenotypes were analyzed by a variety of techniques, including biochemical, molecular, histological, behavioral techniques and electromyography.Results: The TDP-43 transgene was expressed in neurons, astrocytes, and oligodendrocytes in the cortex and predominantly in astrocytes and oligodendrocytes in the spinal cord. The mice developed a reproducible progressive weakness ending in paralysis in mid-life. Detailed analysis showed ~30% loss of large pyramidal neurons in the layer V motor cortex; in the spinal cord, severe demyelination was accompanied by oligodendrocyte injury, protein aggregation, astrogliosis and microgliosis, and elevation of neuroinflammation. Surprisingly, there was no loss of lower motor neurons in the lumbar spinal cord despite the complete paralysis of the hindlimbs. However, denervation was detected at the neuromuscular junction.Conclusions: Low-level TDP-43 overexpression can cause diverse aspects of ALS, including late-onset and progressive motor dysfunction, neuroinflammation, and neurodegeneration. These results demonstrate that modest elevations in TDP-43 expression may underlie not only ALS but also other neuromuscular disorders involving TDP-43 proteinopathy. Because of the predictable and progressive clinical paralytic phenotype, this transgenic mouse model may also be useful in preclinical trial of therapeutics targeting neurological disorders associated with elevated levels of TDP-43.