bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia-inducible factor 2α but not hypoxia-inducible factor-1α increases iron traffic in astrocytes
Authors: Xu Manman , Chen Zhiqiang , Ma Xizhen , Xu Hangrui , Fan Changsheng , Wang Jun , Xie Junxia 
Published: April 2020

Abstract
Background

Disrupted iron homeostasis in the substantia nigra (SN) is an important mechanism in Parkinson’s disease (PD). In our previous studies using cultured neurons, we showed that 6-hydroxydopamine (6-OHDA) treatment increased the expression of divalent metal transporter-1 (DMT1) gating iron influx and decreased the expression of ferroportin 1 (FPN1) gating iron efflux, leading to increased iron deposition. In astrocytes, 6-OHDA increased both DMT1 and FPN1 expressions and iron traffic. However, the underlying mechanisms mediating these processes remain elusive. Hypoxia-inducible factors (HIFs) are important regulators of iron homeostasis.
Methods

Using western blots, we observed HIFs, DMT1 and FPN1 expressions in primary cultured astrocytes and ventral mesencephalic (VM) treated with 6-OHDA, inhibitors of HIF-1α and HIF-2α, protein kinase C (PKC) inhibitor and PKC activator, radical scavenger and inducible NO synthase (iNOS) inhibitor. The ferrous iron traffic of astrocytes was determined by measuring the quenching or reversing of calcein fluorescence.
Results

Using primary rat cell cultures, we observed that 6-OHDA treatment significantly increased the expressions of HIF-1α and HIF-2α in cultured astrocytes but not in VM neurons. Moreover, we observed that HIF-2α inhibitor, but not HIF-1α inhibitor reversed the 6-OHDA-induced upregulation of DMT1 and FPN1 and ferrous iron traffic. Blocking protein kinase C (PKC) pathway by bisindolylmaleimide I hydrochloride (Bisl) or N-acetyl-l-cysteine (NAC) or Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) inhibits Phorbol 12-myristate 13-acetate (PMA) or 6-OHDA induced activation of HIF-2α, whereas activating by PMA or 6-OHDA was sufficient to activate HIF-2α. Notably, blocking of PKC delta (PKC δ) phosphorylation by NAC, or L-NAME inhibits 6-OHDA induced activation of HIF-2α.
Conclusion

Our data indicate that astrocytic HIF-2α, but not HIF-1α, may be an important regulator of DMT1 and FPN1 expressions by activating the PKC -dependent pathway.
An integrated drug repurposing strategy for the rapid identification of potential SARS-CoV-2 viral inhibitors
Authors: Trezza Alfonso , Iovinelli Daniele , Prischi Filippo , Santucci Annalisa , Spiga Ottavia 
Published: April 2020

Abstract
The Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2). The virus has rapidly spread in humans, causing the ongoing Coronavirus pandemic. Recent studies have shown that, similarly to SARS-CoV, SARS-CoV-2 utilises the Spike glycoprotein on the envelope to recognise and bind the human receptor ACE2. This event initiates the fusion of viral and host cell membranes and then the viral entry into the host cell. Despite several ongoing clinical studies, there are currently no approved vaccines or drugs that specifically target SARS-CoV-2. Until an effective vaccine is available, repurposing FDA approved drugs could significantly shorten the time and reduce the cost compared to de novo drug discovery. In this study we attempted to overcome the limitation of in silico virtual screening by applying a robust in silico drug repurposing strategy. We combined and integrated docking simulations, with molecular dynamics (MD), Supervised MD (SuMD) and Steered MD (SMD) simulations to identify a Spike protein – ACE2 interaction inhibitor. Our data showed that Nilotinib and Imatinib bind the receptor-binding domain of the Spike protein with high affinity and prevent ACE2 interaction.
Preventive Strategies for Management of COVID-19 Using Natural Molecules
Authors: Dound Yogesh Arun , Chaudhary Sameer , Chaudhary Sapana Sameer , Ahmad Malik M , Geesi Mohammed H , Alam Pravej 
Published: May 2020

Abstract
The COVID19, a fatal disease by coronavirus (SARS-CoV-2) in late 2019 in China is now pandemic caused severe acute respiratory syndrome. The pandemic of COVID-19 has reached almost all regions of the world including territories with the death toll of more than 35,000. It has been estimated that one out every six-person affected by COVID-19 developed life-threatening conditions. The difficulty is that there are no vaccines or no specific treatment modalities for the management of COVID-19, apart from symptomatic treatments. Efforts for the development of vaccines and other specific treatment modalities are co-ordinated by the World Health Organisation (WHO), with many clinical trials ongoing with modern and traditional medicines. In this regard, various Phyto-actives from the plants are getting analyzed, which has earlier shown to be effective in various viral infections. Therefore, keeping the world scenario and due to the lack of vaccine, we have in silico studied the activity of tetrahydrocurcumin, a major metabolite of curcumin, a household spice, matairesinol, a major compound in wheat bran or flaxseed and vitamin K2-7 against both SARS-CoV's main peptide and COVID-19 Mpro.
Comparison of the effects of and usability of active and active-assistive rehabilitation robots for the upper extremity function among patients with stroke: a single-blinded randomized controlled pilot study
Authors: Park Jin Ho , Park Gyulee , Kim Ha Yeon , Lee Ji-Yeong , Ham Yeajin , Hwang Donghwan , Kwon Suncheol , Shin Joon-Ho 
Published: April 2020

Abstract
Background
Robotic rehabilitation of stroke survivors with upper extremity dysfunction yields different outcomes depending on the robot type. Considering that excessive dependence on assistive force provided by robots may interfere with the patient’s active learning and participation, we hypothesized that the use of an active-assistive robot does not lead to a more meaningful difference with respect to upper extremity rehabilitation than the use of an active robot. Accordingly, we aimed to evaluate the differences in the clinical and kinematic outcomes between active and active-assistive robotic rehabilitation among stroke survivors.
Methods
In this single-blinded randomized controlled trial, we assigned 20 stroke survivors with upper extremity dysfunction (Medical Research Council scale score, 3 or 4) to the active (ACT) and active-assistive (ACAS) robotic rehabilitation groups in a 1:1 ratio and administered 20 sessions of 30-minute robotic intervention (5 days/week, 4 weeks). The primary (Wolf Motor Function Test [WMFT]-score and -time: measures activity), and secondary (Fugl-Meyer Assessment [FMA] and Stroke Impact Scale [SIS] scores: measure impairment and participation, respectively; kinematic outcomes) outcome measures were determined at baseline, after 2 and 4 weeks of the intervention, and 4 weeks after the end of the intervention. Furthermore, we evaluated the usability of the robotic devices by conducting interviews with the patients, therapists, and physiatrists.
Results
In both the groups, the WMFT-score and -time improved over the course of the intervention. Time had a significant effect on the WMFT-score and -time, FMA-UE, FMA-prox, and SIS-strength; group × time interaction had a significant effect on SIS-function and SIS-social participation (all, p < 0.05). The ACT group showed better improvement in participation and smoothness than the ACAS group. In contrast, the ACAS group exhibited better improvement in mean speed.
Conclusions
There were no differences between the two groups regarding the impairment and activity domains. However, the ACT robots were more beneficial than ACAS robots regarding participation and smoothness. Considering the high cost and complexity of ACAS robots, ACT robots may be more suitable for robotic rehabilitation in stroke survivors who can perform voluntary movement.
Trial registration:
The trial was registered retrospectively on 14 March 2018 at ClinicalTrials.gov (NCT03465267).
Identification of Drugs Blocking SARS-CoV-2 Infection using Human Pluripotent Stem Cell-derived Colonic Organoids
Authors: Duan Xiaohua , Han Yuling , Yang Liuliu , Nilsson-Payant Benjamin E. , Wang Pengfei , Zhang Tuo , Xiang Jenny , Xu Dong , Wang Xing , Uhl Skyler , Huang Yaoxing , Chen Huanhuan Joyce , Wang Hui , tenOever Benjamin , Schwartz Robert E. , Ho David. D. , Evans Todd , Pan Fong Cheng , Chen Shuibing 
Published: April 2020

Abstract
The current COVID-19 pandemic is caused by SARS-coronavirus 2 (SARS-CoV-2). There are currently no therapeutic options for mitigating this disease due to lack of a vaccine and limited knowledge of SARS-CoV-2 biology. As a result, there is an urgent need to create new disease models to study SARS-CoV-2 biology and to screen for therapeutics using human disease-relevant tissues. COVID-19 patients typically present with respiratory symptoms including cough, dyspnea, and respiratory distress, but nearly 25% of patients have gastrointestinal indications including anorexia, diarrhea, vomiting, and abdominal pain. Moreover, these symptoms are associated with worse COVID-19 outcomes1. Here, we report using human pluripotent stem cell-derived colonic organoids (hPSC-COs) to explore the permissiveness of colonic cell types to SARS-CoV-2 infection. Single cell RNA-seq and immunostaining showed that the putative viral entry receptor ACE2 is expressed in multiple hESC-derived colonic cell types, but highly enriched in enterocytes. Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo- entry virus, which was further validated in vivo using a humanized mouse model. We used hPSC-derived COs in a high throughput platform to screen 1280 FDA-approved drugs against viral infection. Mycophenolic acid and quinacrine dihydrochloride were found to block the infection of SARS-CoV-2 pseudo-entry virus in COs both in vitro and in vivo, and confirmed to block infection of SARS-CoV-2 virus. This study established both in vitro and in vivo organoid models to investigate infection of SARS-CoV-2 disease-relevant human colonic cell types and identified drugs that blocks SARS-CoV-2 infection, suitable for rapid clinical testing.
Shortages of hospital beds exacerbate severity of COVID-19 outbreaks
Authors: Zhou Weike , Wang Aili , Wang Xia , Cheke Robert A , Tang Sanyi 
Published: April 2020

Abstract
Background: The global outbreak of COVID-19 has caused worrying concern amongst the public and health authorities. The first and foremost problem that many countries face is a shortage of medical resources. The experience of Wuhan, China, in fighting against COVID-19 provides a model for other countries to learn from. Methods: We formulated a piecewise smooth model to describe the limitation of hospital beds, based on the transmission progression of COVID-19, and the strengthening prevention and control strategies implemented in Wuhan, China. We used data of the cumulative numbers of confirmed cases, cured cases and deaths in Wuhan city from 10 January to 20 March, 2020 to estimate unknown parameters and the effective reproduction number. Sensitivity analysis was conducted to investigate the impact of a shortage of hospital beds on the COVID-19 outbreak. Results: Even with strong prevention and control measures in Wuhan, slowing down of the supply rate, reducing the maximum capacity and delaying the intervention time of supplementing hospital beds aggravated the outbreak severity by magnifying the cumulative numbers of confirmed cases and deaths, prolonging the period of the outbreak in Wuhan, enlarging the value of the effective reproduction number during the outbreak and postponing the time when the threshold value is reduced to 1. Conclusions: The quick establishment of the Huoshenshan and Leishenshan Hospitals in a short time and the deployment of mobile cabin hospitals played important roles in containing the COVID-19 outbreak in Wuhan, providing a model for other countries to provide more hospital beds for COVID-19 patients faster and earlier.
Analysis of oral microbiome in chronic periodontitis with Alzheimer’s disease: Pilot study
Authors: Na Hee Sam , Jung Na-Yeon , Choi Suji , Kim Si yeong , Kim Hyun‐Joo , Lee Ju Youn , Choi Jeomil , Kim Yun Hak , Lee Jae-Hyung , Chung Jin 
Published: May 2020

Abstract
Background

Alzheimer's disease (AD) dementia is the most common form of dementia in the elderly. Chronic periodontitis (CP) is a progressive destructive disease in the periodontal tissues, which is also common in the elderly. CP is known to be associated with an increase in cognitive decline in Alzheimer’s disease (AD). Recently, a potential role for pathogenic microbes in the development or exacerbation of AD pathology has been proposed. To reveal the association between periodontitis-related microbes and AD, we investigated the oral microbiome in AD patients with CP.
Methods

Fifteen AD dementia (AD) with CP and 14 cognitively unimpaired (CU) participants with CP were recruited. Buccal, supragingival and subgingival plaque samples were collected with the full-mouth periodontal examination. Alpha diversity, beta diversity, LEfSe (linear discriminant analysis effect size), metabolic pathway prediction and network analysis were applied to compare the microbiome features.
Results

All participants had moderate to severe chronic periodontitis. The level of alpha diversity in subgingival microbiota of the AD group was higher than the CU group. Also, principle coordinate analysis showed significant difference in subgingival samples. When significant taxa were analyzed by LEfSe, various Prevotella spp. were more prevalent in subgingival samples from AD group. Furthermore, subgingival microbiome network analysis showed distinctive network complexity in AD compared to CU group.
Conclusion

We found that subgingival microbiome of AD patients had increased microbial diversity. The composition of subgingival microbiome was different between the AD and the CU groups. This pilot study provides a novel view at the changes of subgingival microbiome in AD patients with CP. Our findings need further well-designed studies with adequate sample size to confirm oral microbiome characteristics in AD with CP.
A lower apatinib dose provides equivalent efficacy and reduced toxicity: A phase II, single-arm study of apatinib and oral etoposide in metastatic breast cancer
Authors: Hu Nanlin , Zhu Anjie , Si Yiran , Yue Jian , Wang Xue , Wang Jiayu , Ma Fei , Xu Binghe , Yuan Peng 
Published: April 2020

Abstract
Background:The effectiveness of antiangiogenic drugs in metastatic breast cancer(MBC) is still unclear. Apatinib is a small tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor 2 (VEGFR-2). We performed this clinical trial to evaluate the efficacy and safety of apatinib and oral etoposide in patients with HER2-negative locally advanced or MBC.Methods:Patients with HER2-negative MBC previously treated with anthracycline and taxanes and failed ≥ 1 prior chemotherapy regimens were recruited. The starting dose of apatinib was 500 mg and 425 mg in patients with Eastern Cooperative Oncology Group (ECOG) scores of 0–1 and 2, respectively. The etoposide capsules were given at 50 mg/m2 on days 1 to 10 for 21 days. The primary end point was progression-free survival (PFS) which is assessed every 6 weeks (RECIST v1.1). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.Results:Thirty-one eligible patients were enrolled. The median follow-up time was 11 months. The median PFS for all patients was 6.93 months (95% confidence interval (CI), 5.97–7.90), and 6.93 months(95% CI 5.27–8.60) and 6.56 months (95% CI 1.41–11.73) for patients with apatinib 425 mg and 500 mg once daily, respectively. The ORR was 35.5% (11/31). The DCR was 87.1% (27/31). The median OS was 20.37 months (95% CI, 11.39–29.34). The median PFS of patients who had hypertension and proteinuria was longer than that for those without hypertension and proteinuria. The most common grade 3/4 treatment-related adverse events(AE) were hypertension (12/31, 38.71%), fatigue (3/31, 9.68%), thrombocytopenia (3/31, 9.68%).Conclusion:Apatinib combined with etoposide capsules is effective and tolerable in heavily pretreated, metastatic HER2-negative breast cancer patients. A lower apatinib dose provide equivalent efficacy and reduced toxicity.
Piezoelectric and pyroelectric properties of Mn-doped 0.36Pb(In1/2Nb1/2)O3-0.36Pb(Mg1/3Nb2/3)O3-0.28PbTiO3 ceramics
Authors: Huang Xiaoli , Tang Yanxue , Wang Feifei , Zhao Xiangyong , Duan Zhihua , Wang Tao , Du Qiuxiang , Wang Jiasheng , Zhou Xingtong , Shi Wangzhou 
Published: April 2020

Abstract
Piezoelectric and pyroelectric properties as well as strain behavior of 0.5 mol% Mn-doped 0.36Pb(In1/2Nb1/2)O3-0.36Pb(Mg1/3Nb2/3)O3-0.28PbTiO3 (Mn-PIMNT) ceramics were studied. High piezoelectric coefficient of d33 = 235 pC/N, planar electromechanical coupling factor of kp = 43.1% and the high-power Figure of Merit (FOM = 60160 pC/N) were achieved in Mn-PIMNT ceramics. Furthermore, the ceramics exhibited high pyroelectric coefficient of p = 4.8×10-4 Cm-2K-1, figures of merit for the current responsivity of Fi = 1.92×10-10 mV-1, the voltage responsivity of Fv = 0.028 m2C-1, and the detectivity of Fd = 2.317×10-5 Pa-1/2 at room temperature. The excellent piezoelectric and pyroelectric properties together with high ferroelectric rhombohedral to tetragonal phase transition temperature of Trt = 146 ℃ and ferroelectric tetragonal to cubic phase transition temperature of TC = 188 ℃ make the Mn-PIMNT ceramics suitable for high-temperature piezoelectric and pyroelectric devices.
Clinical Outcomes of Lateral Lumbar Interbody Fusion Combined with Percutaneous Endoscopic Lumbar Discectomy During the Treatment of Low-grade Spondylolisthesis
Authors: Li Jiaqi , Sun Yapeng , Zhang Wei , Zhang Fei , Guo Lei , Wang Xianzheng , Shen Yong 
Published: May 2020

Abstract
Background

Minimally invasive lateral lumbar interbody fusion (LLIF) in combination with percutaneous endoscopic lumbar discectomy (PELD) can achieve interbody fusion and direct decompression, but their combined use has not been widely reported. In this study, the clinical outcomes of LLIF in combination with PELD in low-grade spondylolisthesis was evaluated, particularly in cases of a requirement for direct decompression.
Methods

Patients with single-level low-grade spondylolisthesis, undergoing LLIF in combination with PELD were included. The severity of lower back and leg pain was reported using visual analog scale (VAS). The Oswestry disability index (ODI) was used to evaluate functional improvements of patients. A comparison of preoperative and postoperative indicators was performed through repeated measures of analysis of variance. P < 0.05 was considered as a statistically significant difference.
Results

A total of 48 patients (20 males and 28 females) were included. The intraoperative blood loss was 112.60ml ± 43.69 and the average operation time was 116.35min ± 22.31. VAS and ODI were significantly improved in all stages after operation. The fusion rate at the final follow-up was 93.7%. No injuries occurred to the vessels, nerves and organs during the perioperative period.
Conclusions

LLIF in combination with PELD achieved adequate decompression and intervertebral fusion, with precise and reliable clinical outcomes. In addition, the procedure was minimally invasive, resulting in small tissue injury and rapid postoperative recovery. Multi-center prospective comparative studies are now needed to further confirm the superiority of this combination.
Identification of new drug treatments to combat COVID19: A signature-based approach using iLINCS
Authors: O’Donovan Sinead M , Eby Hunter , Henkel Nicholas D , Creeden Justin , Imami Ali , Asah Sophie , Zhang Xiaolu , Wu Xiaojun , Alnafisah Rawan , Taylor R. Travis , Reigle James , Thorman Alexander , Shamsaei Behrouz , Meller Jarek , McCullumsmith Robert E 
Published: April 2020

Abstract
The COVID-19 pandemic caused by the novel SARS-CoV-2 is more contagious than other coronaviruses and has higher rates of mortality than influenza. As no vaccine or drugs are currently approved to specifically treat COVID-19, identification of effective therapeutics is crucial to treat the afflicted and limit disease spread. We deployed a bioinformatics workflow to identify candidate drugs for the treatment of COVID-19. Using an “omics” repository, the Library of Integrated Network-Based Cellular Signatures (LINCS), we simultaneously probed transcriptomic signatures of putative COVID-19 drugs and signatures of coronavirus-infected cell lines to identify therapeutics with concordant signatures and discordant signatures, respectively. Our findings include three FDA approved drugs that have established antiviral activity, including protein kinase inhibitors, providing a promising new category of candidates for COVID-19 interventions.
Response to and perception of nurses during the COVID-19: a qualitative assessment
Authors: Hashmi Furqan K. , Iqbal Qaiser , Haider Sajjad , Ahmed Fiaz ud Din , Saleem Fahad , Bashaar Mohammad 
Published: April 2020

Abstract
BackgroundThe COVID-19 outbreak was declared pandemic by the WHO on 11 March 2020. For that reason, we gathered insight from frontline healthcare professionals (nurses) regarding their perceptions, awareness, and familiarity of COVID-19. MethodsBeing a novel outbreak, we opted for a qualitative research design. With the help of a self-constructed and validated interview guide, face-to-face interviews were conducted with nurses to gain an in-depth knowledge. All interviews were audio-taped, transcribed verbatim, and were then analyzed for thematic contents by the standard content analysis framework. ResultsThe saturation was reached at the 12th interview. Two more interviews were carried out to ensure the saturation achieved at the 12th interview. Thematic content analysis yielded four major themes. (1) Perceived knowledge, awareness, and severity of COVID-19, (2) perceived personal capability of handling and managing the COVID-19, (3) perceived organizational capability of handling and managing the COVID-19, and (4) barriers in handling and managing the COVID-19. ConclusionFindings of our study and reservations of our nurses’ highlight areas of concern and scheme of improvement in the effective management of the COVID-19. The respondents are faced with substantial difficulties and barriers in providing healthcare services to patients. We believe that the current study can help in planning policies and generating guidelines that can meet the healthcare needs of the society while managing the COVID-19 as well as for future pandemic outbreaks of the same nature.
Promoting mechanism of electronic shuttle for bioavailability of Fe(III) oxide and its environmental significance
Authors: Yang Yuning , Chen Lei , Jiang Yu , Xu Zheng , Gao Shaobo , Li Mingxiao , Li Rui , Xi Beidou 
Published: April 2020

Abstract
The biological reduction process of Fe(III) not only strongly affects the circulation of C, N, O, P and other elements in the environment, but also plays an important role in the transformation and degradation of organic and inorganic pollutants. Most Fe(III) oxides existing in nature have low bioavailability due to their poor solubility or strongly crystalline form with stable chemical properties. Addition of a substance having redox activity can form an electron shuttle cycle between Fe(III) oxide and the microorganism, which can not only enhance the bioavailability of Fe(III) and accelerate electron transfer, but also improve the removal efficiency of contaminants. This paper compares and analyzes several common redox active substances, for their promoting effect and limiting factors of Fe(III) bioavailability. Moreover, the mechanism by which the electron shuttle promotes the bioavailability of Fe(III) oxide is discussed. This review demonstrates that the electron shuttle promotes the Fe(III) bioreaction process for the degradation and removal of heavy metals, polycyclic aromatic hydrocarbons, azo dyes and other pollutants, which is of great environmental significance.