bluuebunny/crossref_metadata_2025 huggingface dataset:
Implantable Brain-Computer Interface for Volitional Hand Grasp in Spinal Cord Injury
Authors: Jagid Jonathan , Cajigas Iahn , Davis Kevin , Meschede-Krasa Benyamin , Prins Noeline , Gallo Sebastian , Naeem Jasim , Palermo Anne , Wilson Audrey , Guerra Santiago , Parks Brandon , Zimmerman Lauren , Gant Katie , Levi Allan , Dietrich W. Dalton , Fisher Letitia , Vanno Steven , Tauber John , Garwood Indie , Abel John , Brown Emery , Ivan Michael , Prasad Abhishek
Published: January 2021

Loss of hand function after cervical spinal cord injury severely impairs functional independence. We describe a method for restoring volitional control of hand grasp in a subject with complete cervical quadriplegia (C5 ASIA Impairment Scale A) using a portable fully implanted brain-computer interface (BCI) within the home environment. The BCI consists of subdural surface electrodes placed over the dominant-hand motor cortex and connects to a transmitter implanted subcutaneously below the clavicle, which allows continuous reading of the electrocorticographic (ECoG) activity. Movement-intent was used to trigger functional electrical stimulation (FES) of the dominant hand during an initial 29-week laboratory study and subsequently via a mechanical hand orthosis during in-home use. Movement intent information could be decoded consistently throughout the 29-week in-laboratory study with a mean accuracy of 89.0% (range 78-93.3%). Improvements were observed in both the speed and accuracy of various upper extremity tasks, including lifting small objects and transferring objects to specific targets. After study week 23, the subject began to be able to extend his right thumb volitionally in the absence of the FES orthosis. At home decoding accuracy during open-loop trials reached an accuracy of 91.3% (range 80-98.95%) and an accuracy of 88.3% (range 77.6-95.5%) during closed-loop trials. A fully implanted BCI can be safely used to reliably decode movement intent from motor cortex, allowing for accurate volitional control of hand grasp and may potentially re-engage latent neural pathways to allow targeted re-innervation of muscles below the level of injury. (Funded by the Miami Project to Cure Paralysis; ClinicalTrials.gov number, NCT02564419.)
Association Between Gestational Bell’s Palsy and Preeclampsia and Other Pregnancy-Related Metabolic Disorders: A Retrospective Comparative Case Study
Authors: Leelawai Sumonthip , Suwanrath Chitkasaem , Pruphetkaew Nannapat , Chongphattararot Pensri , Sathirapanya Pornchai
Published: January 2021

BackgroundThe associations between gestational Bell’s palsy (GBP) and preeclampsia (PE) and other pregnancy-related metabolic disorders such as gestational hypertension (GHT) and gestational diabetes mellitus (GDM) remain unclear. We aimed to evaluate these associations and to compare the neonatal outcomes between the newborns of pregnant women with and without GBP.MethodsThis was a retrospective 1:5 comparative case study between pregnant women with and without GBP. GBP cases in Songklanagarind Hospital from 2006 to 2016 were enrolled. The exact maternal age and order of gravidity at the onset of GBP were matched. The associations between GBP and PE, GHT and GDM were evaluated comparatively. Also, the outcomes of newborns from the two pregnant women groups were compared and analyzed by univariable analysis (p<0.05).ResultsEight GBP cases out of 8,756 pregnant women were enrolled. Six of the GBP cases were first or second gravidity pregnancies. Five cases developed GBP during the third trimester. Except for significantly higher median systolic and diastolic blood pressures (SBP and DBP) in the GBP cases, we found no significant associations between GBP and PE, GHT or GDM. Additionally, the neonates of the GBP women had significantly lower mean birth weight.ConclusionsWe found that GBP had no associations with PE, GHT or GDM. However, significantly lower birth weight was found in the newborns of the GBP women. The higher median SBP and DBP found in the GBP women may imply that a common pathogenesis of microvasculopathy between GBP and late pregnancy-related complications exists.
The Meaning of Serum CRP, ESR, Platelet Count and Mean Platelet Volume ratio(PC/MPV) and plasma Fibrinogen in the Diagnosis of Periprosthetic Joint Infection
Authors: Huang Jincheng , Zhang Jingyi , Gao Zongyan , Chen Xiao , Dai Zhipeng , Dong Yonghui , Zheng Wendi , Liu Jijun , Zheng Jia , Jin Yi
Published: January 2021

BackgroundThe purpose of this study was to test the meaning of serum CRP, ESR, Platelet Count and Mean Platelet Volume ratio (PC/MPV) and plasma Fibrinogen in periprosthetic joint infection diagnosis. MethodsClinical data of 160 patients diagnosed with osteoarthritis (Group A), PJI (Group B) and aseptic loosening after joint arthroplasy (Group C) were retrospective studied. General data and preoperative serum CRP, ESR, Platelet count to Mean Platelet Volume ratio and plasma Fibrinogen level were recorded and compared.ResultsSerum CRP, ESR, PC/MPV and plasma Fibrinogen expression level in Group B are much higher than Group A and C. When PC/MPV>31.70 was set as the optimum threshold value for the diagnosis of PJI, the specificity of PC/MPV in PJI diagnosis was lower than CRP and ESR, whereas, the sensitivity of PC/MPV in PJI diagnosis was similar with CRP and ESR. When plasma Fibrinogen > 4.01 μg/mL was set as the optimum threshold value for the diagnosis of PJI, the specificity and sensitivity of plasma Fibrinogen in diagnosis of PJI was similar with CRP and ESR. ConclusionPC/MPV should not be used as the first screen marker for PJI diagnosis, whereas, the plasma Fibrinogen can be used as a new marker for PJI diagnosis.
Screening and understanding Li adsorption on 2-dimensional metallic materials by learning physics
Authors: Gong Sheng , Wang Shuo , Zhu Taishan , Chen Xi , Grossman Jeffrey
Published: January 2021

Two-dimensional (2D) materials have received considerable attention as possible electrodes in Li-ion batteries (LIBs), although a deeper understanding of the Li adsorption behavior as well as broad screening of the materials space is still needed. In this work, we build a high-throughput screening scheme that incorporates a learned interaction. First, density functional theory and graph convolution networks are utilized to calculate minimum Li adsorption energies for a small set of 2D metallic materials. The data is then used to find a dependence of the minimum Li adsorption energies on the sum of ionization potential, work function of the 2D metal, and coupling energy between Li+ and substrate. Our results show that variances of elemental properties and density are the most correlated features with coupling. To illustrate the applicability of this approach, the model is employed to show that some fluorides and chromium oxides are potential high-voltage materials with adsorption energies < -7 eV, and the found physics is used as the design principle to enhance the Li adsorption ability of graphene. This physics-driven approach shows higher accuracy and transferability compared with purely data-driven models.
Evaluating the impact of investing in the industry of clinical practice guidelines for health systems
Authors: Hassanien Amal
Published: January 2021

Rationale: This research has been conducted to facilitate evidence-informed policymaking and to help health-care policymakers in Saudi Arabia to decide whether or not a sustainable investment in the CPG industry is socially and economically viable. Objectives: The objective is to investigate: (i) whether the clinical practice guidelines help to improve clinical practice and save costs, and (ii) the views in Saudi Arabia about implementing clinical practice guidelines. Methods: The study employs mixed methods, including: (i) a literature review to evaluate the benefits of implementing clinical practice guidelines, and (ii) an online survey to investigate views about implementing the guidelines' benefits. Results: (i) The clinical practice guidelines do help in improving clinical practice, but the evidence about their impact on saving costs is insufficient in the literature. (ii) The survey demonstrated a high level of awareness among health system actors in Saudi Arabia of the importance of having nationally unified clinical guidelines. Recommendations: Investment in the clinical practice guidelines industry seems socially and economically viable.
An N-of-1 Trial of Itacitinib for a Patient with Aplastic Anemia Associated with a Gain-of-Function Variant in STAT1
Authors: Rosenberg Jacob , Hughes Travis , Peters Joshua , Lareau Caleb , Ludwig Leif , Massoth Lucas , Austin-Tse Christina , Rehm Heidi , Bryson Bryan , Fortune Sarah , Chen Yi-Bin , Shalek Alex , Sykes David
Published: January 2021

An 18-year-old man presented with aplastic anemia, and exome sequencing identified a germline gain-of-function variant in the gene STAT1. Treatment with itacitinib, an investigational selective Janus Kinase 1 (JAK1) inhibitor, resulted in prompt recovery of hematopoiesis. An exhausted CD8+ T cell population and myeloid populations enriched for an interferon-y signature correlated with disease activity. Patient bone marrow sections displayed increased phospho-STAT1 staining, as did other idiopathic aplastic anemia cases, suggesting a shared pathophysiologic mechanism. This study describes the success and mechanism of a molecularly targeted therapy with potential implications for the treatment of aplastic anemias and other autoimmune disorders.
Solubility of the Ketoconazole (an Antifungal Drug) in Supercritical Carbon Dioxide and Menthol as a Cosolvent (Ternary System): Experimental Data and Empirical Correlations
Authors: Sodeifian Gholamhossein , Sajadian Seyed Ali , Razmimanesh Fariba , Hazaveie Seyed Mojtaba
Published: January 2021

One of the main steps in choosing the drug nanoparticle production processes by supercritical carbon dioxide (SC-CO2) is determining the solubility of the solid solute. For this purpose, the solubility of Ketoconazole (KTZ) in the SC-CO2, binary system, as well as in the SC-CO2-menthol (cosolvent), ternary system, was measured at 308–338 K and 12–30 MPa using the static analysis method. The KTZ solubility in the SC-CO2 ranged between 1.70×10− 6 and 8.02×10− 4, while drug solubility in the SC-CO2 with cosolvent varied from 2.7×10− 5 to 1.96×10− 4. This difference indicated the significant effect of menthol cosolvent on KTZ solubility in the SC-CO2. Moreover, KTZ solubilities in the two systems were correlated by several empirical and semiempirical models. Among them, Sodeifian et al., Bian et al., MST, and Bartle et al. models can more accurately correlate experimental data for the binary system than other used models. Also, the Sodeifian and Sajadian model well fitted the solubility data of the ternary system with AARD,%= 6.45, Radj= 0.995.
Design and Fabrication of Soft X ray Suppermirrors
Authors: Wang Hanlin , Wang Haifeng , Ren Shuai , Zhou Peng , Zheng Xin , Chen Bo , Chen Zhongjun , Liu Shuhu , Wang Xiaodong
Published: January 2021

W/Si, Ir/SiC, and Pt/C supermirrors were designed by block method and fabricated by magnetron sputtering method. The glancing incident angles are 1.0, 1.4 and 1.7 degree. Pt/C supermirrors show better spectral results than W/Si, Ir/SiC. Pt/C supermirrors also have good angular tolerance, which will benefit opt-mechanic alignment. In addition, Pt layer as outmost one can withstand harsh space environment.
Factors Influencing Mental Health among Chinese Medical and Non-medical Students in the Early Stage of COVID-19 Pandemic
Authors: Xiong Peng , Ming Wai-kit , Zhang Caiyun , Bai Jian , Luo Chaohua , Cao Wenyuan , Zhang Fan , Tao Qian
Published: January 2021

Background: The 2019 coronavirus disease (COVID-19) pandemic is a public health emergency of international concern. This study aimed to assess the psychological outcomes and their influencing factors among medical and non-medical university students during the COVID-19 pandemic in China. Methods: A cross-sectional online survey using structured questionnaires was conducted from 20 February to 20 March 2020. Psychological outcomes were assessed according to the Depression, Anxiety, and Stress Scale (DASS-21). Influencing factors were assessed by COVID-19 knowledge, mindful coping scale, and sense of control scale.Results: Our sample comprises of 563 university students (male = 172, mean age = 21.52). Among them, 382 are medical students. Among the participants, 12.26%, 18.47%, and 8.53% of them have moderate to severe levels of depression, anxiety, and stress symptoms, respectively. Compared with the non-medical students, the medical students had a higher knowledge level of COVID-19, a higher sense of awareness, and fewer mental health symptoms. After controlling the covariance, perceived constrains of sense of control were negatively associated with depression, anxiety, and stress among both medical and non-medical students. Prevention of negative emotions by mindful coping was negatively associated with depression and anxiety among non-medical students. Knowledge of COVID-19 is not associated with mental distress among medical and non-medical students.Conclusions: During the COVID-19 pandemic in China, the mental health of university students was affected. Our findings suggested that a sense of control is a protective factor for both medical and non-medical students, while mindful coping is a protective factor for only non-medical students.
Self-Renewal Assessment and Isolation of CD133 Positive Cancer Stem Cells from the Ovarian A2780 Cell Line
Authors: Keyvani Vahideh , Moghbeli Meysam , Nezhad Seyed Reza Kazemi , Abbaszadegan Mohammad Reza
Published: January 2021

Background: Ovarian cancer (OC) is the 7th most common type of cancer and the 5th cause of cancer-related death among women worldwide. It is a heterogeneous disease which is quite variable from the genomic and histopathological aspect. In addition to the usual treatments for ovarian cancer, its recurrence is quite common, mainly due to lack of complete eradication of cancer stem cells. These cells have different properties such as self-renewal ability and stemness property, including proliferation.Method: In the present study, we isolated cancer stem cells with the CD133 surface marker from the ovarian A2780 cell line and examined the stemness property and self-renewal ability of these cells. Initially, CD133 surface marker expression in this cell line was assessed by the flow cytometry technique. Then, the isolation of these cells was performed by the Magnetic-activated cell sorting (MACS) method. Flow cytometry (FCM) was also used to confirm the isolation efficiency. The levels of mRNA expression were evaluated in several stem cell markers in CD133+ cells compared with CD133- cells. Moreover, the self- renewal ability of the isolated cells was investigated in serum-free culture medium.Results: Ovarian cancer stem cells (OCSCs) with CD133 surface marker showed high expression of some stemness markers such as Sox2, Nanog, Oct4, ABCG2, ALDH1, LGR5 and Msi. These cells also had the ability to regenerate themselves in a serum-free environment.Conclusion: Cancer stem cells can be isolated through surface markers by the MACS technique; they have stemness and self-renewal properties. So, the CD133 surface marker can be introduced as a key CSC marker in the isolation, characterization and targeted therapy of ovarian cancer patients.
Recurrent Postmenopausal Bleeding: Just Endometrial Disease or Ovarian Sex Cord Stromal Tumor? A Case Report and Literature Review
Authors: Wang Jiao , Yang Qing , Zhang Ningning , Wang Dandan
Published: January 2021

Background: Postmenopausal bleeding (PMB) is a common gynecologic complaint among elderly women, and endometrial hyperplasia is a common cause of this bleeding. Ovarian fibromas are the most common ovarian sex cord stromal tumors (SCST). They arise from non-functioning stroma, rarely show estrogenic activity, and stimulate endometrial hyperplasia, leading to abnormal vaginal bleeding. Case presentation: We report herein the case of a 64-year-old Chinese woman who presented with recurrent PMB. A sex-hormone test revealed her estrogen level was significantly higher than normal, and other causes of hyperestrogenism had been excluded. In the past 7 years, the patient had undergone four curettage-and-hysteroscopy procedures due to recurrent PMB and endometrial hyperplasia. Finally, the culprit behind the rise in estrogen – an ovarian cellular fibroma with estrogenic activity – was found in the fifth operation.Conclusions: Ovarian cellular fibromas occur insidiously, and some may have endocrine functions. For postmenopausal patients with recurrent PMB and endometrial thickening indicated by ultrasonography, it is recommended they undergo sex-hormone testing while waiting for results regarding the pathology of the endometrium. If the estrogen level remains elevated, even if the imaging does not indicate an ovarian tumor, the clinician should consider the possibility of an ovarian SCST and follow the patient closely. Once the tumor is found, no matter the size, it should be removed as soon as possible to avoid endometrial lesions caused by long-term estrogen stimulation. More studies are needed to confirm whether preventive total hysterectomy with bilateral salpingo-oophorectomy should be recommended for postmenopausal women with recurrent bleeding whose estrogen levels are higher than normal, even when the auxiliary examination does not indicate ovarian mass. It is possible this could avoid the physical and psychological burden caused by repeated curettage.
COVID-19 Associated Cerebral Infarction in an Elderly Patient: A Case Report
Authors: Xie Jumin , Feng Changwu , Chen Jie , Wang Zhu
Published: January 2021

Background: The 2019 Severe Acute Respiratory Syndrome Coronavirus (SARS-Cov-2) had been declared an emergency at the beginning and eventually progressing to a pandemic by World Health Organization. To date, more than 78,194,9471 people confirmed infected by SARS-Cov-2 and 1,736,752 dead, globally. Various characteristics were described in the case reports and clinical studies after SARS-Cov-2 hitting the whole world. Case presentation：COVID-19 cases accompanied with cerebral infraction were hardly reported. Herein, we present a 74-yesrs-old patient who got SARS-Cov-2 infected at the late January and developed cerebral infraction. After accurate treatment, the old patient recovered and discharged from hospital on April 3, 2020. We keep on supervising the patient, after 7 months long physical condition surveillance, the patient live a normal life with on obvious sequelae detected. Conclusions: In this paper, we present a elder COVID-19 case associated with cerebral infraction and whole process management in treatment. The elder patients lived a normal life after discharging from Huangshi central hospital which we believed that early introducing of traditional Chinese medicine played important roles in COVID-19 treatment. We aimed to broaden new cognition towards SARS-Cov-2 infection and suggest therapy to COVID-19 cases with cerebral infraction.
A Modified Risk Detection Approach of Biomarkers by Frailty Effect on Multiple Time-to-Event Data
Authors: Bhattacharjee Atanu , Vishwakarma Gajendra , Banerjee Souvik
Published: January 2021

Multiple indications of disease progression found in a cancer patient by loco-regional relapse, distant metastasis and death. Early identification of these indications is necessary to change the treatment strategy. Biomarkers play an essential role in this aspect. The biomarkers can influence how particular cancer behaves and how it may respond to a specific treatment. The survival chance of a patient is dependent on the biomarker, and the treatment strategy also differs accordingly, e.g., the survival prediction of breast cancer patients diagnosed with HER2 positive status is different from the same with HER2 negative status. This results in a different treatment strategy. So, the heterogeneity of the biomarker statuses or levels should be taken into consideration while modelling the survival outcome. This heterogeneity factor which is often unobserved, is called frailty. When multiple indications are present simultaneously, the scenario becomes more complex as only one of them can occur, which will censor the occurrence of other events. Incorporating independent frailties of each biomarker status for every cause of indications will not depict the complete picture of heterogeneity. The events indicating cancer progression are likely to be inter-related. So, the correlation should be incorporated through the frailties of different events. In our study, we considered a multiple events or risks model with a heterogeneity component. Based on the estimated variance of the frailty, the threshold levels of a biomarker are utilised as early detection tool of the disease progression or death. Additive-gamma frailty model is considered to account the correlation between different frailty components and estimation of parameters are performed using Expectation-Maximization Algorithm. This work is about handling multiple indications by frailty model and promote personalised medicine. With the extensive algorithm in R, we have obtained the threshold levels of activity of a biomarker in a multiple events scenario.
An Exploratory Study on The Association Between Gender and Factors That Influence Animal-Source Food Dietary Intake for Households In Lower-Income Urban Informal Settings of Nairobi, Kenya
Authors: Ngutu Mariah , Bukachi Salome A. , Muthiru Ann W. , Lépine Aurélia , Kadiyala Suneetha , Domínguez-Salas Paula
Published: January 2021

Background: Low-quality monotonous diets dominated by starchy foods are a major problem confronting resource-constrained settings worldwide including poor households in the urban informal settings of Nairobi, Kenya. This low-quality dietary intake is fueled by socio-economic disparities further complicated by gender hegemonies that influence decision making in food choice and consumption. This places the population, especially women of reproductive age and young children, at a risk of micronutrients deficiencies, such as anemia. Animal-source foods (ASFs) are high-quality nutrient-dense products that supply essential amino-acids, vitamins and minerals, to reduce stunting and micronutrient deficiencies. Previous research showed that the poorest households in Nairobi, Kenya, had low Animal-source foods (ASFs) consumption.Food security and nutrition dimensions of food security such as the gendered dimensions have been the main focus in most development interventions. However, there still exists gaps especially at the household level that try to understand the association between gender and factors that influence animal-source food dietary intake.Methods: An exploratory qualitative study was carried out to establish the association between gender and factors that influence animal-source foods dietary intake for households in lower-income urban informal settings of Nairobi, Kenya. We utilized 19 focus group discussions with embedded participatory exercises and 60 in-depth interviews differently for men and women alongside unstructured observations to enable in-depth exploration of ASFs consumption and choice determinants.Results: Gender and related factors including decision making, power position dynamics of men and women as well as coping mechanisms were seen to influence household ASF dietary intake. Both men and women had a role providing for food budgets and also deciding on when and what ASF would be consumed in their households. Notably, men and women in the informal low-income settings face socio-economic challenges in planning for and sustaining household food needs including ASF.Conclusion: Nutrition and health interventions and programs tackling malnutrition in lower-income households need to consider the gender and associated factors as identified in this exploratory research. These factors are seen as intersecting with the household economic status and sociocultural practices to influence ASF dietary intake including choice and consumption.
Association between egg consumption and arterial stiffness: a longitudinal study
Authors: Ji Naiwen , Huang Zhe , Zhang Xinyuan , Sun Yuanyuan , Ye Shumao , Chen Shuohua , Tucker Katherine , Wu Shouling , Gao Xiang
Published: January 2021

Background
Inconsistent associations between egg consumption and cardiovascular disease (CVD) risk have been observed in previous studies. This study aims to longitudinally investigate the association between egg consumption and altered risk of arterial stiffness, a major pre-clinical pathogenic change of CVD, which was assessed by brachial-ankle pulse wave velocity (baPWV).
Methods
A total of 7,315 Chinese participants from the Kailuan Study, free of CVD and cancer were included in this study. Egg consumption was assessed by a semi-quantitative validated food frequency questionnaire in 2014. baPWV was repeatedly measured at baseline and during follow-up (mean follow-up: 3.41 years). General linear regression was used to calculate means of baPWV change rate across different egg consumption groups, adjusting for age, sex, baseline baPWV, healthy eating index, total energy, social-economic status, blood pressure, obesity, smoking, lipid profiles, and fasting glucose concentrations.
Results
Compared to the annual baPWV change rate in participants with 0-1.9 eggs/wk (adjusted mean: 35.9 ± 11.2 cm/s/y), those consuming 3-3.9 eggs/wk (adjusted mean: 0.2 ± 11.4 cm/s/y) had the lowest increase in baPWV during follow-up (P-difference = 0.002). Individuals with low (0-1.9 eggs/wk) vs. high (5 + eggs /wk) egg intake showed similar changes in baPWV.
Conclusions
In this large-scale longitudinal analysis, we did not find a significant difference in arterial stiffness, as assessed by baPWV level, between low and high egg consumption groups. However, moderate egg consumption (3-3.9 eggs/wk) appeared to have beneficial effects on arterial stiffness.
Multi-DOA Estimation Based on the KR Image Tensor and Improved CNN
Authors: Yuan Ye , Wu Shuang , Yang Yong , Yuan Naichang
Published: January 2021

In this paper, we propose an improved convolutional neural network (CNN) to solve the multi-DOA estimation problem. We use Khatri-Rao (KR) product to obtain the KR image tensor of covariance matrix and use the proposed estimation CNN to process the tensor. In order to increase the generalization of the proposed CNN and adapt the multi-label classification problem, we use the curriculum learning scheme (CLS) and partial label strategy (PLS) to develop an efficient training procedure. We implement several experiments to demonstrate the satisfying performance of the proposed estimation method. The simulation results show that our proposed method can finish the high resolution multi-DOA estimation use only a few sensors. Furthermore, the proposed method can obtain high estimation accuracy under low SNR situations and use fewer snapshots.
Clinical application of 3D virtual and printed models for cerebrovascular diseases
Authors: Bae Jin Woo , Lee Da Yeong , Pang Chang Hwan , Kim Jeong Eun , Park Chul-Kee , Lee Doohee , Park Sang Joon , Cho Won-Sang
Published: January 2021

Three-dimensional (3D) printing techniques are rapidly advancing in the medical industry and in clinical practice. We aimed to evaluate the usefulness of 3D virtual and printed models of 12 representative cerebrovascular diseases, consisting of 9 intracranial aneurysms, 2 cavernous malformations and 1 arteriovenous malformation. Using the software we developed, segmentation of raw data and rendering and modification for 3D virtual models were processed mostly automatically. Among the 12 virtual models, 9 (excluding 3 intracranial aneurysms) were printed with a commercial 3D printing system and materials. Most intracranial structures were satisfactorily made, including the skull, brain, vessels, thrombus, tentorium and major cranial nerves. The 3D models were thought to be very helpful in experiencing the operative views from various directions in advance and in selecting an appropriate surgical approach. However, it was still difficult to discriminate small vessels and cranial nerves, to feel a realistic tactile sense and to directly perform presurgical simulations, such as dissection, removal, clipping and microanastomosis. With advancements in radiological resolution, processing techniques and material properties, 3D modeling is expected to simulate real brain tissues more closely.
Simvastatin Influences Selected Aspects of Duchenne Muscular Dystrophy Pathology in a Mouse Model
Authors: Mucha Olga , Podkalicka Paulina , Kaziród Katarzyna , Dulak Józef , Łoboda Agnieszka
Published: January 2021

Background: Duchenne muscular dystrophy (DMD) is an incurable disease, caused by the mutations in the DMD gene, encoding dystrophin, an actin-binding cytoskeletal protein. Lack of functional dystrophin results in muscle weakness, degeneration, and as an outcome cardiac and respiratory failure. As there is still no cure for affected individuals, the pharmacological compounds with the potential to treat or at least attenuate the symptoms of the disease are under constant evaluation. The pleiotropic agents, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, have been suggested to exert beneficial effects in the mouse model of DMD. On the other hand, they were also reported to induce skeletal-muscle myopathy.Methods: Several methods including functional assessment of muscle function via grip strength measurement and treadmill test, enzymatic assays, histological analysis of muscle damage, gene expression evaluation, and immunofluorescence staining were conducted to study simvastatin-related alterations in mdx mice.Results: In our study, simvastatin treatment of mdx mice did not result in improved running performance; however, some beneficial effect was observed when grip strength was evaluated. Creatine kinase and lactate dehydrogenase activity, markers of muscle injury, were diminished after simvastatin delivery in mdx mice. Nevertheless, no significant changes in inflammation, fibrosis, and necrosis were noted. Interestingly, simvastatin treatment led to the decreased mRNA level of embryonic myosin heavy chain isoform, a declined percentage of centrally nucleated myofibers, and miR-1 upregulation, suggesting an alteration in the muscle regeneration. However, similarly to the changes noticed in the expression of some angiogenic factors, the obtained results are muscle-dependent, being prominent in gastrocnemius muscle but not in the diaphragm.Conclusion: In conclusion, we suggest that simvastatin has the potential to ameliorate selected aspects of DMD pathology; however, possible benefits still need to be thoroughly tested.
Site-Specific Chemical Doping Reveals Electron Atmospheres at the Surfaces of Organic Semiconductor Crystals
Authors: He Tao , Stolte Matthias , Wang Yan , Renner Rebecca , Ruden Paul , Würthner Frank , Frisbie C. Daniel
Published: January 2021

Chemical doping controls the electronic properties of organic semiconductors, but so far, doping protocols and mechanisms are less developed than in conventional semiconductors. Here we describe a unique, site-specific, n-type surface doping mechanism for single crystals of two benchmark organic semiconductors that produces dramatic improvement in electron transport and concurrently provides unprecedented evidence for doping-induced space charge. The surface doping chemistry specifically targets crystallographic step edges, which are known electron traps, simultaneously passivating the traps and releasing itinerant electrons. The effect on electron transport is profound: field effect electron mobility increases by as much as a factor of 10 and its temperature dependent behavior switches from thermally-activated to band-like. Our findings suggest new site-specific strategies to dope organic semiconductors that differ from the conventional redox chemistry of randomly distributed substitutional impurities. Critically, they also verify the presence of dopant-induced electron atmospheres, confirming long-standing expectations for organic systems from conventional solid-state theory.
Novel Biallelic TLE6 Variants Induce Preimplantation Embryonic Lethality That Cannot be Rescued by IVF or ICSI
Authors: Zhang Manyu , Liu Chunyu , Chen Beili , Lv Mingrong , Zou Huijuan , Liu Yajing , Gao Yang , Wang Tianjuan , Xing Qiong , Zhu Yutong , Wu Huan , Zhang Zhiguo , Zhou Ping , Wei Zhaolian , He Xiaojin , Xu Yuping , Cao Yunxia
Published: January 2021

Background: Preimplantation embryonic lethality is a rare cause of primary female infertility. Transducin-like enhancer of split 6 (TLE6) is a maternal effect gene which encodes a component of the subcortical maternal complex located in the oocytes and early embryos. It has been reported that biallelic variants in TLE6 can lead to preimplantation embryonic lethality. However, the incidence of TLE6 variants in patients with preimplantation embryonic lethality is not fully understood.Methods: Whole-exome sequencing and bioinformatics analyses were used to analyze a cohort of 28 patients with preimplantation embryonic lethality. We retrospectively analyzed the process and outcome of their attempts at in vitro fertilization and intracytoplasmic sperm injection. Results: In this study, four patients (14.29 %, 4/28) from three unrelated families in a cohort of 28 individuals with preimplantation embryonic lethality were identified as carrying biallelic TLE6 variants, including two homozygous variants and one compound heterozygous variant. These novel frameshift variants in TLE6 caused truncation of the TLE6 protein likely impairing its function. Immunofluorescence staining of oocytes for TLE6 indicated that it is localized in the oocyte cytoplasm, and that TLE6 was almost absent in the oocytes of the patients carrying biallelic TLE6 variants compared with normal control oocytes. A retrospective analysis showed that the four affected individuals underwent a total of nine in vitro fertilization and intracytoplasmic sperm injection attempts, in which a total of 119 metaphase II oocytes were retrieved, but none of them obtained high-quality blastocysts or obtained a successful pregnancy. However, one of these patients became pregnant on the first attempt using donated oocytes.Conclusions: Biallelic TLE6 variants cause preimplantation embryonic lethality that cannot be rescued by in vitro fertilization or intracytoplasmic sperm injection. Thus, oocyte donation may be the preferred treatment for patients harboring biallelic TLE6 variants.
RGS12 as a Novel Maternal-Effect Gene Causes Arrest at the Pronuclear Stage of Human Zygote
Authors: Ma Tianzhong , Zhang Chengpeng , Zhou Songxia , Xie Xuezhen , Chen Jingyao , Wang Jing , Gao Sini , Mai Ruiqin , Zhang Guohong
Published: January 2021

Background: Early embryonic arrest is one of the major causes of female infertility after in vitro fertilization (IVF), but the causal gene of arrest at the pronuclear (PN) zygote stage is largely unknown. Results: To understand this process, we recruited a family characterized by recurrent PN arrest during IVF cycles and performed whole-exome sequencing. The missense variant c.C1630T (p.R544W) in RGS12 was responsible for a phenotype characterized by paternal transmission. RGS12 controls Ca2+ oscillation, which is required for oocyte activation after fertilization. Single-cell transcriptome profiling of PN-arrest zygotes revealed defective established translation, RNA processing and cell cycle, which explained the failure of complete oocyte activation. Furthermore, we identified proximal genes involved in Ca2+ oscillation–cytostatic factor–anaphase-promoting complex (Ca2+ oscillation–CSF–APC) signaling, including upregulated CaMKII, ORAI1, CDC20, and CDH1 and downregulated EMI1 and BUB3. The findings indicated abnormal spontaneous Ca2+ oscillations leading to oocytes with prolonged low CSF and high APC level, which resulted in defective nuclear envelope breakdown and DNA replication. The changes in levels of critical genes were confirmed by examining other independent PN-arrest zygotes. However, the PN-arrest zygote phenotype was not consistent with that of RGS12-deficient mice, thereby indicating species-specific functions between human and mouse. Conclusion: Our findings expand our knowledge of the genetic determinants of human early embryonic arrest at the PN stage and provide guidance for selecting clinically infertile individuals with PN-arrest zygotes for Ca2+ intervention.
Prevalence of Y Chromosome Microdeletion Among Mongolian Infertile Men With Azoospermia and Severe Oligozoospermia
Authors: Damdinsuren Erdenesuvd , Naidansuren Purevjargal , Gochoo Mendsaikhan , Choi Bum-Chae , Choi Min Youp , Baldandorj Bolorchimeg
Published: January 2021

Backgound: Y chromosome microdeletions are the second most common genetic causes in male infertility. The aim of the present study was to reveal the patterns of Y chromosome microdeletions among Mongolian infertile men. Method: A descriptive study was performed to 75 infertile men during February 2017 to December 2018. Y chromosome microdeletions were identified by PCR. Semen parameters, hormonal levels, testis biopsy were determined. All collected data were evaluated with Statistical Package for Social Sciences (SPSS, version 22.0).Results: Among 75 infertile men, 2 cases of Y chromosome microdeletions were determined (2.66%). The first case had AZFa complete deletion and the other one had AZFc partial deletion. The azoospermia patient with AZFa complete deletion had Sertoli cell only syndrome in the testis biopsy, FSH 58.0 mIU/ml and LH 12.0 mIU/ml. The azoospermia patient with AZFc partial deletion showed FSH 23.85 mIU/ml and LH 13.01 mIU/ml. Serum FSH level was significantly higher in the Y chromosome microdeletion patients (p value 0.016). Conclusion: This study determined Y chromosome microdeletion among Mongolian infertile men to be at 2.66%. Our results showed FSH level is the best predictor of a successful TESE. However, best cut off value for FSH was 9.69 mIU/ml with a sensitivity and specificity 85.6% and 83.3% respectively. There is a possibility that sperm retrieval will be difficult from the TESE since the testicular tissue is severely damaged. The findings can be applied to IVF and Assisted Reproductive Techonology, and our results will help clinicians improve treatment management for Mongolian infertile couples.
Parent-Adolescent Communication on Sexual and Reproductive Health Issues and Associated Factors Among Secondary and Preparatory School Students in Agaro town, Jimma Zone Southwest Ethiopia
Authors: Abdissa Daba , Sileshi Workitu
Published: January 2021

Background: Adolescents are rarely provided with adequate information about their development, especially in regard to sexuality. This problem has exposed the adolescents to the risk of many sexual and reproductive health problems. Parents have significant role to reduce sexual risk behaviors and promote healthy adolescent sexual development. Hence, the aim of this study was to assess parent-adolescent communication on SRH issues among secondary and preparatory school students in Agaro town, Southwest Ethiopia, 2019. Methods: School based cross-sectional study was conducted from April 13-20/2019 using stratified random sampling technique. Data were collected using pretested interviewer-administered structured questionnaire entered into Epi data version 3.1; and analyzed using SPSS version 20. A variable having a p-value of <0.25 in the bivariable model was subjected to multivariable analysis to avoid the confounding variable’s effect. Adjusted odds ratios were calculated at the 95% confidence interval and considered significant with a p-value of <0.05.Results: A total of 315 students were included to the study. The mean age of the respondents was 20.2±2.6 years. The study finding showed that 61.3% of the participants were discussed on SRH issues with their parents. Educational status of mother [primary education (AOR=3.67; 95%CI:1.93,6.97),secondary education(AOR:2.86;95%CI:1.2,6.8)],educational status of father[primary education (AOR=5.8;95%CI:2.8,12.3,secondary education (AOR=3.21; 95%CI:1.55,6.59)],having family size of <5 (AOR= 6.4; 95%CI: 3.36,12.37) and having boy/girlfriend(AOR=1.99; 95%CI:1,3.8) were significantly associated with parent adolescent communication. Conclusion: About two third of the participants communicate with their parents. parents’ educational status, family size of <5 and having boy/girlfriend were significantly associated with the communication.
Nrf2 is required for structural and metabolic maturation of human induced pluripotent stem cell-derived cardiomyocytes
Authors: Zhang Xinyuan , Ye Liang , Xu Hao , Zhou Qin , Tan Bin , Yi Qin , Yan Liang , Xie Min , Zhang Ying , Tian Jie , Zhu Jing
Published: January 2021

Background
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) hold great promise for regenerative medicine and in vitro screening. Despite displaying key cardiomyocyte phenotypic characteristics, they more closely resemble fetal/neonatal cardiomyocytes and are still immature, these cells mainly rely on glucose as a substrate for metabolic energy, while mature cardiomyocytes mainly employ oxidative phosphorylation of fatty acids. Studies showed that the alteration of metabolism pattern from glycolysis to oxidative phosphorylation improve the maturity of hiPSC-CMs. As a transcription factor, accumulating evidences showed the important role of Nrf2 in the regulation of energy metabolism, which directly regulates the expression of mitochondrial respiratory complexes. Therefore, we hypothesized that Nrf2 is involved in the maturation of hiPSC-CMs.
Methods
The morphological and functional changes related to mitochondria and cell maturation were analyzed by knock-down and activation of Nrf2.
Results
The results showed that the inhibition of Nrf2 led to the retardation of cell maturation. The activation of Nrf2 leads to a more mature hiPSC-CMs phenotype, as indicated by the increase of cardiac maturation markers, sarcomere length, calcium transient dynamics, the number and fusion events of mitochondria, and mitochondrial respiration. Bioinformatics analysis showed that in addition to metabolism-related genes, Nrf2 also activates the expression of myocardial ion channels.
Conclusions
These findings indicated that Nrf2 plays an important role in the maturation of hiPSC-CMs. The present work provides greater insights into the molecular regulation of hiPSC-CM metabolism and theoretical basis in drug screening, disease modeling and alternative treatment.
MicroRNA in Children with Asthma: Findings from Bronchoalveolar Lavage Fluid
Authors: Liu Min , Lv Jian-Hai , Wu Lei , Tang Lan-Fang
Published: January 2021

Objective: To investigate the pathogenesis of miRNA in asthma by measuring the microRNAs (miRNAs) levels in the bronchoalveolar lavage fluid (BALF) cells of children with asthma.Methods: A total of 15 children with asthma were enrolled as the asthma group and another 13 children who were subjected to airway foreign removal within 24 hours were enrolled as the control group. The levels of miRNAs were measured by miRNA microarray and verified by qRT-PCR. The expression of target genes E-cadherin was assessed as well.Results: A total of 65 miRNAs in the BALF cells of the asthma group were different from those in the control group. Six miRNAs of miR-34/449 family and seven miRNAs of miR-200 family were decreased. For 13 differentially expressed miRNAs, qRT-PCR confirmed that 10 miRNAs were consistent with the results of miRNAs microarray, including miR-34b-3p, miR-34b-5p, miR-34c-3p, miR-34c-5p, miR-200a-3p, miR-200a-5p, miR-200b-3p, miR-200b-5p, miR-200c-3p, miR-141-3p. E-cadherin, the predicted target of miR-34/449 family and miR-200 family, was down-regulated in children with asthma as well.Conclusions: These data suggested that miRNAs, especially the miR-34/449 and miR-200 families, were involved in the mechanism of childhood asthma by regulating E-cadherin expression. Further studies on the mechanism of miRNAs in asthma are required.
Expression Profiling of the Dof Gene Family Under Abiotic Stresses in Spinach
Authors: Yu Hongying , Ma Yaying , Lu Yijing , Yue Jingjing , Ming Ray
Published: January 2021

DNA-binding with one finger (Dof) transcription factors are plant-specific transcription factors involved in numerous pathways of plant development, especially in respond to abiotic stresses. Although genome-wide analysis of this gene family has been performed in many species, Dof genes in spinach have not been thoroughly analyzed. We performed a genome-wide analysis and characterization of Dof gene family in spinach. Twenty two Dof genes were identified and classified into four groups with nine subgroups, which was further corroborated by gene structure and motif analyses. Ka/Ks analysis revealed that SoDofs were subjected to purify selection. Using Cis-acting elements analysis, SoDofs were involved in plant growth and development, plant hormones and stress responses. Expression profiling demonstrated that SoDofs expressed in leaf and inflorescence, and responded to cold, heat, and drought stresses. SoDof22 expressed the highest level in male flowers and under cold stress. These results provided a genome-wide analysis of SoDof genes, their gender- and tissue-specific expression, and response to abiotic stresses. The knowledge and resources gained from these analyses will benefit spinach improvement.
Stress-induced Differential Gene Expression in Cardiac Tissue
Authors: de Carvalho Ana Elisa , Cordeiro Marco , Rodrigues Luana , Ortolani Daniela , Spadari Regina
Published: January 2021

The stress response is adaptive and aims to guarantee survival. However, the persistence of a stressor can culminate in pathology. Catecholamines released as part of the stress response over activate beta adrenoceptors (β-AR) in the heart. Whether and how stress affects the expression of components of the intracellular environment in the heart is still, however, unknown. This paper used microarray to analyze the gene expression in the left ventricle wall of rats submitted to foot shock stress, treated or not treated with the selective β2-AR antagonist ICI118,551 (ICI), compared to those of non-stressed rats also treated or not with ICI, respectively. The main findings were that stress induces changes in gene expression in the heart and that β2-AR plays a role in this process. The vast majority of genes disregulated by stress were exclusive for only one of the comparisons, indicating that, in the same stressful situation, the profile of gene expression in the heart is substantially different when the β2-AR is active or when it is blocked. Stress induced alterations in the expression of such a large number of genes seems to be an adaptive reaction, aimed at sustaining heart function and protecting cardiomyocytes from apoptosis.