bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of SARS-CoV2 Main Protease Coldspots Suitable for Drug Targeting
Authors: Krishnamoorthy Navaneethakrishnan , Fakhro Khalid 
Published: December 2020

Abstract
Most attempts to target the novel coronavirus SARS-CoV2 are focusing on the main protease (Mpro) 1,2. We already have access to high resolution 3D-structures of the SARS-CoV2 Mpro, which were developed with inhibitors as co-crystals using X-ray crystallography 3-9. However, >19,000 missense mutations in the Mpro have already been reported 10. The mutations encompassing 282 amino acid positions and these “hotspots” might change the Mpro structure and activity, potentially rendering novel antivirals and vaccines ineffective. Here we identified 24 mutational “coldspots” that have resisted mutation since the virus was first detected. We compared the structure-function relationship of these coldspots with several SARS-CoV2 Mpro X-ray crystal structures. We found that three coldspot residues (Leu141, Phe185 and Gln192) help to form the active site, while six (Gly2, Arg4, Tyr126, Lys137, Leu141 and Leu286) contribute to dimer formation that is required for Mpro activity. Importantly, seven coldpots are conserved among other coronaviruses and available on the surface of the active site and at the dimer interface for targeting. The identification and short list of these coldspots offers a new perspective to target the SARS-CoV2 Mpro while avoiding mutation-based drug resistance.
A Novel lncRNA&nbsp;ARST&nbsp;Represses Glioma Progression by Inhibiting ALDOA-mediated Actin Cytoskeleton Integrity
Authors: Sun Jun , He Dong , Fu Yibing , Zhang Rui , Guo Hua , Wang Zhaojuan , Wang Yanan , Gao Taihong , Wei Yanbang , Guo Yuji , Pang Qi , Liu Qian 
Published: December 2020

Abstract
Background: Glioma is one of the most aggressive malignant brain tumors that is characterized with highly infiltrative growth and poor prognosis. ARST is a novel lncRNA which expression is significantly decreased in the patients with glioblastoma multiforme. However, the exact mechanisms of ARST in gliomagenesis are largely unknown. Methods: The expressions of ARST in the glioma samples and cell lines were analyzed by qRT-PCR. FISH was utilized to detect the distribution of ARST in the glioma cells. CCK-8, EdU and flow cytometry were used to examine cellular viability, proliferation and apoptosis. Transwell and wound-healing assays were performed to determine the migratory and invasive abilities of the cells. Intracranial tumorigenesis models were established to explore the roles of ARST in vivo. RNA pulldown assay was used to examine proteins that bound to ARST. The activities of key enzymes in the glycolysis and production of lactate acid were measured by colorimetry. In addition, RIP, Co-IP, western blot, immunofluorescence were used to investigate the interaction and regulation between ARST, F-actin, ALDOA and cofilin.Results: In this study, we reported that ARST was downregulated in the gliomas. Overexpression of ARST in the glioma cells significantly suppressed various cellular vital abilities such as cell growth, proliferation, migration and invasion. The tumorigenic capacity of these cells in vivo was reduced as well. We further demonstrated that the tumor suppressive effects of ARST could be mediated by a direct binding to a glycolytic enzyme aldolase A (ALDOA), which together with cofilin, keeps the polymerization and depolymerization of actin filaments in an orderly dynamic equilibrium. Upregulation of ARST interrupted the interaction of ALDOA and actin cytoskeleton, which led to a rapid cofilin-dependent loss of F-actin stress fibers. Conclusions: Taken together, it is concluded that ARST performs its function via a non-metabolic pathway associated with ALDOA, which otherwise modifies the morphology and invasive properties of the glioma cells. This has added new perspective to its role in tumorigenesis, thus providing potential target for glioma diagnosis, therapy, and prognosis.
Why does mode of conception affect early breast-feeding outcomes? A retrospective cohort study
Authors: Weng Shiue-Shan , Chien Li-Yin , Chang Min 
Published: December 2020

Abstract
Background: Women who conceived through Assisted Reproductive Technology (ART) may experience poorer breast-feeding outcomes compared to women who conceived naturally; nevertheless, the mechanism of this relationship has not been explored. This study aimed to examine the effect of mode of conception on breast-feeding outcomes during the first two months postpartum and identify the potential pathways for this relationship.Methods: A retrospective cohort study was conducted in a sample of 5,474 women with live births using hospital administrative data from January 2014 through December 2018. Participants were classified by mode of conception as follows: fertile women who conceived naturally (fertile women; n=4,363), women with infertility who conceived naturally (sub-fertile women; n=706), and women with infertility who conceived through ART (women with infertility; n=405). The patterns of infant feeding were acquired at hospital discharge, the first week, the first month, and the second month postpartum. Binary and multinomial logistic regression and causal mediation analyses were performed.Results: Infertile and sub-fertile women had 34% (95% CI 1.03, 1.73) and 60% (95% CI 1.11, 2.31) increased risks of introducing formula prior to the first week postpartum, respectively, and 31% (95% CI 1.01, 1.70) and 59% (95% CI 1.10, 2.31) higher risks of exclusive breastfeeding for less than one week during the first two months postpartum, respectively, compared to fertile women. The relationships were mediated through delivery complications, multiple gestations, preterm delivery, low birth weight, and admission to neonatal/paediatric intensive care units (NICU/PICU). The path with the highest proportion mediated was through multiple gestations (60.47% for infertile women) and admission to NICU/PICU (68.60-72.61%). The effect of mode of conception on breastfeeding outcomes was not significant in cases of no maternal and infant morbidities. Conclusions: During the first two months postpartum, infertile and sub-fertile women both had short duration (<7 days) of exclusive breastfeeding and introduction of formula prior to the first week postpartum. The relationships were mainly mediated through multiple gestations and admission to NICU/PICU. Designing programmes to reduce adverse maternal and infant health events, like a single embryo transfer policy, is suggested to improve perinatal outcomes, together with the following breast-feeding outcomes.
The Protect Role of Serum Uric Acid to Premature Rupture of Membranes in Gestational Diabetes: a Cross-sectional Study
Authors: Guo Meixiang , Lu Jun , Hu Xiaowen , Hou Wenjing , Yu Xuemei , Pang Shuguang 
Published: December 2020

Abstract
Background: Uric acid has strong antioxidant activity whereas its oxidative damage is closely related to many diseases. We assessed the association between serum uric acid (SUA) levels and premature rupture of membranes (PROM) in pregnant women with Gestational diabetes (GDM) in china. Method: In this cross-sectional study, a total of 456 pregnant women were enrolled. Anthropometric parameters for pregnant women were collected within 12 weeks of gestation. Weight gain during pregnancy was obtained from patients’ record. GDM was diagnosed according to 75-g oral glucose tolerance tests at 24-28th week’s gestation, and SUA was determined simultaneously. PROM was identified as the natural rupture of fetal membranes before the first stage of labor. Logistic models were fitted to identify the presence of PROM using clinical characteristics with (Model 1) or without serum uric acid (Model 2).Results: There exist differences in BMI, haemoglobin A1c, fasting blood glucose, 1-hour postprandial glucose, 2h PG, insulin levels, weight gain during pregnancy, the rate of macrosomia, PROM between women with and without GDM (all P<0.05). Furthermore, individuals with PROM had lower level of SUA than those without PROM in GDM women (P=0.030). The odds ratio of PROM decreases with the increase of SUA level. The area under the receiver operating characteristic curves for PROM based on Model 1 was larger than that in Model 2 (0.86 versus 0.71, p<0.05).Conclusion: Elevated relatively SUA levels at the 24-28th weeks of gestation were associated with a lower risk of PROM in women with GDM. SUA may be a protective factor for PROM in GDM patient. The optimal concentration of uric acid in different diseases and different populations needs to be further studied.
Myogenic Progenitor Cell Transplantation for Muscle Regeneration Following Hindlimb Ischemia and Reperfusion&nbsp;
Authors: Messner Franka , Thurner Marco , Müller Jule , Blumer Michael , Hofmann Julia , Marksteiner Rainer , Couillard-Despres Sebastien , Troppmair Jakob , Öfner Dietmar , Schneeberger Stefan , Hautz Theresa 
Published: December 2020

Abstract
BackgroundMuscle is severely affected by ischemia/reperfusion injury (IRI). Quiescent satellite cells differentiating into myogenic progenitor cells (MPC) possess a remarkable regenerative potential. We herein established a model of local application of MPC in murine hindlimb ischemia/reperfusion to study cell engraftment and differentiation required for muscle regeneration.MethodsA clamping model of murine (C57b/6J) hindlimb ischemia was established to induce IRI in skeletal muscle. After 2 hours (h) warm ischemic time (WIT) and reperfusion, reporter protein expressing MPC (TdTomato or Luci-GFP, 1x106 cells) obtained from isolated satellite cells were injected intramuscularly. Surface marker expression and differentiation potential of MPC were analyzed in vitro by flow cytometry and differentiation assay. In vivo bioluminescence imaging and histopathologic evaluation of biopsies were performed to quantify cell fate, engraftment and regeneration.Results 2h WIT induced severe IRI on muscle, and muscle fiber regeneration as per histopathology within 14 days after injury. Bioluminescence in vivo imaging demonstrated reporter protein signals of MPC in 2h WIT animals and controls over the study period (75 days). Bioluminescence signals were detected at the injection site and increased over time. TdTomato expressing MPC and myofibers were visible in host tissue on postoperative days 2 and 14, respectively, suggesting that injected MPC differentiated into muscle fibers. Higher reporter protein signals were found after 2h WIT compared to controls without ischemia, indicative for enhanced growth and/or engraftment of MPC injected into IRI-affected muscle antagonizing muscle damage caused by IRI.ConclusionWIT-induced IRI in muscle requests increased numbers of injected MPC to engraft and persist, suggesting a possible rational for cell therapy to antagonize IRI. Further investigations are needed to evaluate the regenerative capacity and therapeutic advantage of MPC in the setting of ischemic limb injury.
Methane Emissions Against the Background of Natural and Mining Conditions in the Budryk and Pniówek Mines in the Upper Silesian Coal Basin (Poland)
Authors: Dreger Marcin , Kędzior Sławomir 
Published: December 2020

Abstract
The paper presents the variability of hard coal output, methane content and methane emissions into coal workings and into the atmosphere from the two most methane-gassy coal mines in Poland, Budryk and Pniówek, which are both incorporated in the Jastrzębie Coal Company. The Budryk mine is one of the youngest mines in Poland, but it is the most methane-gassy as well. In 2016, the total CH4 emissions exceed 140 million of m3. This large increase in methane emissions to mine workings is primarily related to the increase in the depth of coal extraction (up to 1290 m) and, consequently, the rapid increase in the methane content in coal seams (up to 10-12 m3 / Mg coaldaf). On the other hand, in the Pniówek mine, methane emission was the highest at the beginning of the study period (1986-1991). During the following years emission decreased to the values of less than 140 million of m3, which were still one of the largest amounts of emitted methane in the entire Upper Silesian Coal Basin. The vertical distribution of methane content, different than in the Budryk mine, and the presence of a secondary high methane zone at the Carboniferous top, seem to be decisive for the long-term distribution of methane emissions in the Pniówek mine. The coexistence of natural factors, such as the geological structure and gas distribution, as well as mining-related factors, i.e. the depth of mining, the concentration of coal extraction determines the temporal variability of methane emissions in the studied mines.
Health-related Quality of Life in Medical Personnel on the Peace Ark Hospital Ship During a Long Voyage: A Cohort Study
Authors: Liu Xu , Tang Bihan , Han Yingnan , Zhang Hailing , Hu Chaoqun , Zhao Fangjie , zhang lulu 
Published: December 2020

Abstract
Background The Chinese hospital ship “Peace Ark” has conducted nine overseas humanitarian missions. Methods Research indicated long-distance voyages significantly impact seafarers’ physical and mental health. This study investigated changes in and influencing factors for medical professionals’ health-related quality of life (HRQoL) during a 2017 humanitarian mission (8 countries, 155 days). Using a cohort study design, 90 medical professionals’ HRQoL was assessed (via the SF-12) pre-voyage and after 5 months at sea. Results Pre-voyage, mean physical component scale (PCS) and mental component scale (MCS) scores were 52.34 (SD 5.07) and 53.03 (SD 6.40), respectively—significantly higher than in the general Chinese population (p < 0.0001). Afterwards, PCS and MCS scores declined by 3.9867 (SD 6.03) and 5.70 (SD 7.03), respectively. PCS scores were negatively associated with female gender (p = 0.004). Compared to administrative staff, doctors (p < 0.001) and nurses (p < 0.001) showed less deviation in PCS scores. Lower MSC scores were associated with older age (p = 0.011) and less family support (p = 0.0165). Conclusions Long-term voyages negatively impacted HRQoL in medical personnel. Thus, prior to similar future humanitarian missions, selection criteria and training procedures for medical personnel should be optimized, thereby increasing their confidence and social support.
Reference Range of Fetal thorax using Two-dimensional and Three-dimensional Ultrasound VOCAL Technique and Application in Fetal Thoracic Malformations
Authors: Lian Xihua , Xu Zhenhong , Zheng Liping , Zhu Zhixing , Ejiwale Tofunmi , Kumar Ayush , Cai Peiya , He Shaozheng , Liu Shunlan , Zhang Ying , Lyu Guorong 
Published: December 2020

Abstract
Background: To establish the normal reference range of fetal thorax by two-dimensional (2D) and three-dimensional (3D) ultrasound VOCAL technique and evaluate the application in diagnosing fetal thoracic malformations. Methods: A prospective cross-sectional study was undertaken involving 1077 women who have a normal singleton pregnancy at 13-40 weeks gestational age (GA). 2D ultrasound and 3D ultrasound VOCAL technique were utilized to assess fetal thoracic transverse diameter, thoracic anteroposterior diameter, thoracic circumference, thoracic area, lung volume, thoracic volume and lung-to-thoracic volume ratio. The nomograms of 2D and 3D fetal thoracic measurements were created to GA. 50 cases were randomly selected to calculate intra- and inter-observer reliability and agreement. In addition, the case groups including congenital skeletal dysplasia (SD) (15), congenital diaphragmatic hernia (CDH) (30), pulmonary sequestration (PS) (25) and congenital cystic adenomatoid malformation (CCAM) (36) were assessed by the nomograms and followed up subsequently.Results: Both 2D and 3D fetal thoracic parameters increased with GA using a quadratic regression equation. The intra- and inter-observer reliability and agreement of each thoracic parameter were excellent. 2D fetal thoracic parameters can initially evaluate the fetal thoracic development and diagnose the skeletal thoracic deformity, and lung volume, thoracic volume and lung-to-thorax volume ratio are practical to diagnose and differentiate CDH, PS and CCAM.Conclusion: We have established the normal fetal thoracic reference range at 13-40 weeks, which has a high value in diagnosing congenital thoracic malformations.
Human Umbilical Cord-Derived Mesenchymal Stem Cells Alleviate Acute Lung Injury Caused by Severe Burn via Secreting TSG-6 and Inhibiting Inflammatory Response
Authors: Hu Xiaohong , Liu Lingying , Wang Yu , Li Zhongyuan , Yu Yonghui , Chai Jiake , Liu Yanan 
Published: December 2020

Abstract
Objectives To investigate whether hUC-MSCs attenuated severe burn-induced ALI and the effects were based on TSG-6 secreted from hUC-MSCs.Method Rat model was established and evaluated as follows：Anires2005 animal pulmonary function tester for pulmonary function; micro-CT scanner for lung imaging manifestations; Cytokine expression was measured by ELISA assay, both inflammatory cells infiltration and lung injury were assessed by immunohistochemistry assay.Results In vitro, TSG-6 levels in serum from burn group were significantly increased than that of the sham group. In vivo, TSG-6 levels of lung tissues and serum in burn+ hUC-MSCs group were significantly increased than that of in the burn group. Higher parameters of the airway resistance（Ri, Re, etc）were markedly decreased and the disordered lung texture and funicular density shadows were significantly improved after hUC-MSCs administration. Both in lung tissues and serum, increased levels of pro-inflammatory cytokines（TNF-α, IL-1β, IL-6）were remarkably decreased but anti-inflammatory cytokine IL-10 increased after hUC-MSCs administrations (p<0.05). These significant positive effects after hUC-MSCs transplantation did not occur in the Burn+siTSG-6 group.Conclusions Intra-tracheal implantation of hUC-MSCs had been an effective treatment for severe burn-induced ALI via promoting TSG-6 secretion and inhibiting inflammatory reaction in lung tissue.
Ultra-Broadband, Lithography-Free, Omnidirectional, and Polarization-Insensitive Perfect Absorber
Authors: Chen Tse-An , Yub Meng-Ju , Lu Yu-Jung , Yen Ta-Jen 
Published: December 2020

Abstract
Perfect absorbers (PAs) at near infrared allow various applications such as biosensors, nonlinear optics, color filters, thermal emitters and so on. These PAs, enabled by plasmonic resonance, are typically powerful and compact, but confront inherent challenges of narrow bandwidth, polarization dependence, and limited incident angles as well as requires using expensive lithographic process, which limit their practical applications and mass production. In this work, we demonstrate a non-resonant PA that is comprised of six continuous layers of magnesium fluoride (MgF2) and chromium (Cr) in turns. Our device absorbs more than 90% of light in a broad range of 900-1900 nm. In addition, such a planar design is lithography-free, certainly independent with polarization, and presents a further advantage of wide incidence up to 70°. The measured performance of our optimized PA agrees well with analytical calculations of transfer matrix method (TMM) and numerical simulations of finite element method, and can be readily implemented for practical applications.
Disparities in Characteristics, Symptoms and mtDNA Influence on Ovarian Cancer Patients From South Indian Population
Authors: Iyer Mahalaxmi , Venkatesan Dhivya , Jayaramayya Kaavya , Subramaniam Mohana Devi , Sennimalai Ramya , Giridharan Bupesh , Nachimuthu Senthil Kumar , Vellingiri Balachandar , Sivanandan Santhy Kumaran , Narayanasamy Arul 
Published: December 2020

Abstract
Ovarian cancer (OC) is a complex multifactorial malignancy, ranking as second most common reproductive cancer in India. The purpose of this study was to compare whether different characteristics combined with hormonal and genetic influence among the urban, rural and tribal populations affected with OC would have a significant impact on OC incidence. To address this challenge, we designed a statistical approach that combines individual-level epidemiological data from both OC patients and controls from designed study populations using questionnaires. A total of (n=72) OC patients were obtained from several oncological clinics, hospitals and population-based surveys from various districts of South Indian population. Using validated hormonal biomarkers, we estimated hormonal profiles in both OC subjects and controls to measure the role of hormones in OC severity and incidence. Further we conducted mitochondrial gene sequencing, we found 5 nucleotide changes among which MT9140 C>T) was the predominant in OC subjects. In conclusion, this kind of study would be the first of its kind, where population-based epidemiological surveys serve as keys for comparing the characteristic factors and genetic influence associated with OC incidence. Hence, we strongly recommend that frequent conduction of epidemiological studies and health awareness camps would be beneficial to overcome such lethal conditions.
Human Herpes Virus Type 6 is Associated with CNS Infections in Children in Sudan
Authors: Abdelrahim Nada Abdelghani , Mohammed Nahla , Evander Magnus , Ahlm Clas , Fadl-Elmula Imad Mohammed 
Published: December 2020

Abstract
Objective HHV-6 is increasingly recognized as febrile agent in children, however, less is known in sub-Saharan African countries. In here, we aimed to investigate the involvement of HHV-6 in pediatric CNS infections in Khartoum, Sudan. This report is part of a larger study on the microbial aetiologies of CNS infections in this population. Results Out of 503, 13 (2.6%) CSF specimens were positive for HHV-6 DNA which constituted 33% (13/40) of cases with proven infectious meningitis. Median Ct for all HHV-6 positive specimens was 38 with range of 31.9 to 40.8. Median virus copy was 281.3/PCR run (1x105 virus copies/ml CSF) with range of 30 to 44x103 copies/PCR run (12x103 and 18x106 virus copies/ml CSF). All positive patients presented with fever, vomiting and 86% with seizures. Male to female ratio was 1:1; 50% were toddlers, 42% infants and 8% teenagers. Most (83%) were admitted in the dry season and 17% in the rainy season. CSF leukocytosis was seen in 33%. Normal and low CSF glucose levels were seen in 86% and 14%, respectively. CSF proteins levels were low in 14% and high in 43%. In conclusion, HHV-6 is common in CNS infections in children in Sudan.
The Kebab Technique: Using a Bipolar Pencil to Retrieve a Dropped Nucleus via a Small Incision
Authors: Aso Hiroshi , Yokota Harumasa , Hanasaki Hirotsugu , Yamagami Satoru , Nagaoka Taiji 
Published: December 2020

Abstract
We developed a new method to retrieve a dropped nucleus via a small incision using bipolar pencils, the kebab technique, to solve the lack of small-gauge fragmatomes, and the expense and toxicity of perfluorocarbon liquids (PFCL). A total of 8 eyes in 6 patients underwent this technique and were reviewed. After vitrectomy, the dropped nucleus was lifted from the retina by adhesion with a bipolar pencil, and phacoemulsification was performed while rotating the lens. The outcome measures were best-corrected visual acuity (BCVA), intraocular pressure (IOP), and corneal endothelial cell density before and after surgery. Surgical indications included zonular weakness, trauma, acute angle closure attack, and phacolytic glaucoma. At 1 month, BCVA improved from a mean ± SD 1.67 logMAR (± 0.90) to 1.14 logMAR (± 1.01). The mean preoperative intraocular pressure (IOP) was 24.5 (± 16.8) mmHg and postoperative IOP was 11.0 (± 2.8) mmHg. The mean preoperative corneal endothelial cell count was 2600 (322) cells/mm2 (one eye was unmeasurable) and postoperative corneal endothelial cell count was 2387 (± 431) cells/ mm2. There were no postoperative complications. The retrieval of a dropped nucleus using a bipolar pencil enables small incisions without using PFCL.