bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystal-Structures-Guided Design of Fragment-Based Drugs for Inhibiting the Main Protease of SARS-CoV-2
Authors: Luan Binquan , Huynh Tien
Published: October 2020

Since the beginning of the COVID-19 pandemic, researchers and scientists across the globe are racing to find a cure for the highly contagious infectious disease caused by the SARS-CoV-2 virus. Despite many promising ongoing progress, there are currently no FDA approved drugs to treat infected patients. Among the various protein targets of SARS-CoV-2 virus, the main protease (Mpro) has attracted most interests. Recently, the crowdsourcing of drug discovery for inhibiting Mpro have yielded
a plenty of drug fragments resolved inside the active site of Mpro via the crystallography method. Following the principle of fragment-based drug design (FBDD), we are motivated to design a potent drug molecule through merging several of these newly discovered drug fragments. Among various designed ligands, we found that B19 by merging three fragments JFM, U0P and HWH is the most stable one, evidenced through extensive (~10 μs totally) all-atom molecular dynamics simulation. We further estimated that the binding free energy of B19 is comparable or even a little better than that of a native protein ligand processed by Mpro. Our promising results suggest that B19 can potentially be an efficacious drug molecule for inhibiting Mpro of SARS-CoV-2.
Factors Associated with Non-Adherence to Social Distancing Rules During The COVID-19 Pandemic: A Logistic Regression Analysis
Authors: Hills Stephen James , Eraso Yolanda
Published: October 2020

Background: On March 23, 2020, the government of the United Kingdom told the British people to stay home, an unprecedented request designed to limit the spread of the COVID-19 virus and stop the National Health Service from being overwhelmed. Methods: This study undertook a cross-sectional design to survey a convenience sample of 681 residents of North London on their social distancing behaviours, demographics, housing situation, politics, psychology and social support using an online questionnaire. Logistic regression was used to measure the associations between these explanatory factors and non-adherence to all social distancing rules and intentional non-adherence to social distancing rules.Results: The majority (92.8%) of participants did not adhere to all social distancing rules and nearly half (48.6%) engaged in intentional non-adherence of rules. The odds of not adhering to all social distancing rules increased if a participant was not identified as highly vulnerable to COVID-19 [OR=4.5], had lower control over others’ distancing [OR=.724], had lower control over responsibilities for which coming into contact with others was unavoidable [OR=.642], and if social distancing behaviours were reported after lockdown was first relaxed [OR=.261]. The odds of intentionally not adhering to social distancing rules increased if a participant had a lower intention to socially distance [OR=.468], had lower control over others’ distancing [OR=.829], had a doctoral degree compared to a master’s degree [OR=.332], a professional qualification [OR=.307], a bachelor’s degree [OR=.361] or work-related qualification [OR=.174], voted for the UK Government compared to not voting for the Government [OR=.461], perceived higher normative pressure from neighbours [OR=1.121] and had greater support from friends [OR=1.465]. Conclusions: Non-adherence to all social distancing rules had a stronger association with vulnerability to COVID-19 and control over social distancing, whereas intentional non-adherence had a stronger association with intention and anti-social psychological factors. It is recommended that people living in high-risk environments, such as those living in houses of multiple occupancy, should be specially supported to not have to leave their home, that public health messaging should emphasise shared responsibility and public consciousness and that there should be greater policing, larger fines and more direct issuing of fines.
Vital signs effectively predict non-hypoglycaemia in patients with altered mental status in pre-hospital settings: A retrospective analysis
Authors: Mizu Daisuke , Matsuoka Yoshinori , Huh Ji Young , Ariyoshi Koichi
Published: October 2020

BackgroundBlood glucose (BG) measurement by paramedics for patients with altered mental status is recommended as pre-hospital care in Japan. Therefore, paramedics prioritise BG measurement over transport to hospital even in emergency conditions such as hypotension or hypoxaemia. The purpose of this study was to examine the relationship between BG levels and vital signs, and to evaluate whether vital signs are effective in determining the necessity of BG measurement in pre-hospital settings. MethodsWe extracted data of patients who had BG measurements performed by paramedics in Kobe City from April 2015 to March 2019. We retrospectively investigated patient age, sex, presence of hypoglycaemia (BG level < 50 mg/dL) and vital signs. If a patient did not have hypoglycaemia and was transported to the Kobe City Medical Centre General Hospital, a final diagnosis was obtained. Patients aged below 15 years, and those with BG measurement errors, missing vital sign data, or a Japan Coma Scale 0 and I-digit codes were excluded. The χ2 test and Mann-Whitney U test were used for statistical analysis, and P<0.05 was considered statistically significant. ResultsOf the 1,791 patients, 1,242 were eligible for analysis (mean age, 71.9 years; 805 [58%] male). Hypoglycaemia was observed in 324 patients (26.1%). Of the 918 non-hypoglycaemic patients, 253 (27.6%) were transported to our hospital and stroke was the most common final diagnosis (61 patients [24.1%]). The non-hypoglycaemic group had more elderly patients than the hypoglycaemic group (median 73 vs. 76 years; P < 0.01). A significant difference in each vital sign were noted between hypoglycaemic and non-hypoglycaemic groups, with body temperature showing the highest difference between groups (area under the curve, 0.71; 95% confidence interval [CI], 0.68-0.74). Furthermore, in cases with systolic blood pressure being over 100 mmHg and body temperature being 38°C or less, it was highly unlikely that hypoglycaemia caused impaired consciousness (likelihood ratio 0.12 and 0.16; 95% CI 0.05-0.25 and 0.06-0.35, respectively). ConclusionWhen considering pre-hospital hypoglycaemia assessment, vital signs are an effective index. If patients have significant hypotension or high fever, paramedics should consider immediate transport rather than BG measurement.
The Association of Treatment Facility Type With the Survival of Brain Metastases Patients Regardless of the Primary Site Cancer
Authors: AMIN SABER Ali , Baine Michael , Meza Jane , Lin Chi
Published: October 2020

Background. Cancer patients with brain metastases (BMs) require multidisciplinary care, and treatment facility may play a role. This study aimed to investigate the impact of receiving treatment at academic centers on the overall survival (OS) of cancer patients with brain metastases (BMs) regardless of the primary cancer site.Methods. This retrospective analysis of the National Cancer Database (NCDB) included patients diagnosed with non-small cell lung cancer, small-cell lung cancer, other types of lung cancer, breast cancer, melanoma, colorectal cancer, and renal cancer and had brain metastases at the time of diagnosis. The data were extracted from the de-identified file of the NCDB, a joint program of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The Cox proportional hazard model adjusted for age of diagnosis, race, sex, place of living, income, education, primary tumor type, year of diagnosis, chemotherapy, radiation therapy (RT), and surgery of the primary cancer site was used to determine treatment facility-associated hazard ratios (HR) for survival. Overall survival was the primary outcome which was analyzed with multivariable Cox proportional hazards regression modeling. Results. A total of 93,633 patients were analyzed, among whom 31,579/93,633 (34.09%) were treated at academic centers. Based on the log-rank analysis, patients who received treatment at an academic facility had significantly improved median OS (6.18, CI: 6.05-6.31 vs. 4.57, CI: 4.50-4.63; p <0.001) months compared to patients who were treated at non-academic facilities. In the multivariable Cox regression analysis, receiving treatment at an academic facility was associated with significantly improved OS (HR: 0.85, CI: 0.84-0.87; p <0.001) compared to the non-academic facility. Conclusions. In this extensive analysis of the NCDB, receiving treatment at academic centers was associated with significantly improved OS compared to treatment at non-academic centers.
An Assessment and Mapping of Coastal Flooding in Niger-Delta; a case study of Bonny, Okrika and Ogu/Bolo of Rivers State
Authors: Agu Christian Chijioke , Ibrahim Asma
Published: October 2020

Background: This research looks at the assessment and mapping of coastal flooding in Niger-Delta region of Nigeria, staring at the three local governments (Bonny, Okrika, and Ogu/Bolo) in Rivers State that lies at intervals the shores of Atlantic Ocean. Result: At the analysis it was found that most of the study areas lies at the creek and with the steady rise of the sea level, as a result of increase in temperature, most of the study area will have steady occurrence of flooding. Conclusion: Adaptation measures like dike construction, maintenance of natural dune systems, protection of coastal ecosystems, planting of vegetation around the coastal areas and different flood proofing and accommodation activities should be put in place to checkmate flooding in those areas.
Using characterization techniques for determining the history of a 2 millennia old kettle made of bronze alloyed with iron
Authors: Kotlar Marta , Matijaković Nives , Desnica Vladan , Marusic Katarina
Published: October 2020

A bronze kettle dating from the 1st to 2nd Century was found in a riverbed of the Kupa river in Croatia. After excavation it spent another 50 years in a depot of a museum in atmospheric conditions prior to starting the conservation treatment and our studies. A study on the surface layers development was performed to determine the history of the object. This study is a demonstration of how such analysis can be used to reconstruct what the object went through during its life span.It was determined that the kettle is made of low-tin bronze, called mild bronze, with addition of iron, aluminum, calcium and nickel. Using iron for alloying copper is unusual since pure iron is generally not added to bronze, thus the presented case is a rare subject. Presence of cassiterite SnO2 showed that the kettle was used for preparing food on open fire prior to ending up in the river. While being in the riverbed malachite formed on the kettle. After longer exposure to the river Si-oxides and CaCO3 formed on the surface of the kettle, over malachite. It was shown that the kettle probably had a ferrous alloy handle which degraded and disappeared in time. After excavation, the kettle came again in an oxygen-enriched atmosphere and developed additional surface layers over the malachite layer.
Neutrophil-to-lymphocyte Ratio as a Predictor of Mortality in ICU Patients: An Analysis of MIMIC-III Database
Authors: Wu Xie , Su Zhanhao , Luo Qipeng , Li Yinan , Wang Hongbai , Liu Qiao , Yan Fuxia
Published: October 2020

Background: Identifying high-risk patients in intensive care unit (ICU) is very important because of the high mortality rate. Existing scoring systems are numerous but lack effective inflammatory markers. Our objective was to identify and evaluate a low-cost, easily accessible and effective inflammatory marker that can predict mortality in ICU patients.Methods: We conducted a retrospective study using data from the Medical Information Mart for Intensive Care III database. We first divided the patients into the survival group and the death group based on in-hospital mortality. Receiver operating characteristic analyses were performed to find the best inflammatory marker (i.e. neutrophil-to-lymphocyte ratio, NLR). We then re-divided the patients into three groups based on NLR levels. Univariate and multivariate logistic regression were performed to evaluate the association between NLR and mortality. The area under the curve (AUC), Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) were used to assess whether the incorporate of NLR can improve the predictive power of existing predictive model. Results: A total of 21,822 patients were included in this study, with an in-hospital mortality rate of 14.43%. Among all inflammatory marker in routine blood test results, NLR had the best predictive ability, with a median (interquartile range) NLR of 5.40 (2.95, 10.46) in the survival group and 8.32 (4.25, 14.75) in the death group. We then re-divided the patients into low (≤1), medium (1-6) and high (≥6) groups based on NLR levels. Compared with the median NLR group, the in-hospital mortality rates were significantly higher in the low (odds ratio [OR] = 2.09; 95% confidence interval [CI], 1.64 to 2.66) and high (OR=1.64; 95%CI, 1.50-1.80) NLR groups. The addition of NLR to Simplified Acute Physiology Score II (SAPS II) improved the AUC from 0.789 to 0.798 (P<0.001), with NRI of 16.64% (P<0.001) and IDI of 0.27% (P<0.001).Conclusion: NLR is a good predictor of mortality in ICU patients, both low and high levels of NLR are associated with elevated mortality rate. The inclusion of NLR might improve the predictive power of SAPS II.
Surprisingly Long Lifetime of Methacrolein Oxide, an Isoprene Derived Criegee Intermediate, Under Humid Conditions
Authors: Lin Yen-Hsiu , Yin Cangtao , Takahashi Kaito , Jr-Min Jim
Published: October 2020

Ozonolysis of isoprene, the most abundant alkene in the atmosphere, produces three distinct Criegee intermediates (CIs): CH2OO, methyl vinyl ketone oxide (MVKO) and methacrolein oxide (MACRO). Here we investigated the UV-visible spectroscopy and reaction kinetics of thermalized MACRO. An extremely fast reaction of anti-MACRO with SO2 has been found with a rate coefficient of (1.5±0.4)x10−10 cm3 s−1 at 298 K (150−500 Torr), which is ca. 4 times the value for syn-MVKO. However, the reaction of anti-MACRO with H2O has been observed to be quite slow with a rate coefficient of (8±6)x10−17 cm3 s−1 at 298 K (300 to 500 Torr), which is smaller than literature values by 1 or 2 orders of magnitude. Our results indicate that anti-MACRO has an atmospheric lifetime much longer than previously thought, resulting in a much higher steady-state concentration. Owing to larger reaction rate coefficient, the impact of anti-MACRO on the oxidation of atmospheric SO2 would be substantial, even larger than that of syn-MVKO.
Beta-cells from patients with COVID-19 and from isolated human islets exhibit ACE2, DPP4, and TMPRSS2 expression, viral infiltration and necroptotic cell death
Authors: Steenblock Charlotte , Richter Stefanie , Berger Ilona , Barovic Marko , Schmid Janine , Schubert Undine , Jarzebska Natalia , von Mässenhausen Anne , Linkermann Andreas , Schürmann Annette , Pablik Jessica , Evert Katja , Rodionov Roman , Semenova Natalia , Zinslering Vsevolod , Gainetdinov Raul , Baretton Gustavo , Lindemann Dirk , Solimena Michaele , Ludwig Barbara , Bornstein Stefan
Published: October 2020

Here we report a possible mechanistic link between coronavirus disease 2019 (COVID-19) and diabetes. In addition to its known role on the respiratory system, the human coronavirus SARS-CoV-2 has been shown to affect the endocrine system including the pancreas 1-4. It has been suggested that the virus can induce type 1 diabetes 5-8. Therefore, we isolated human pancreatic islets and examined the expression of angiotensin-converting enzyme 2 (ACE2) and the protease TMPRSS2, known to be important for SARS-CoV-2 entry 9. Furthermore, we investigated the expression of an alternative entry receptor, dipeptidyl peptidase-4 (DPP4 also known as CD26) 10. We found all three proteins expressed in pancreatic beta-cells and confirmed that beta-cells are permissive to infection with SARS-CoV-2 pseudoviruses. Additionally, we performed a comprehensive analysis of ACE2, TMPRSS2 and DPP4 expression in pancreata of 10 patients who died of COVID-19. We report significant variation between the samples and detected the highest levels of ACE2 and DPP4 expression in patients exhibiting SARS-CoV-2 infiltration shown by confocal microscopy, RNAscope and electron microscopy. Furthermore, necroptotic cell death was observed in beta-cells of the COVID-19 patients. Taken together, these data suggest that SARS-CoV-2 viral infection of pancreatic beta-cells may trigger necroptosis and islet impairment.
Phosphate Sequestration from Aqueous Solutions Using a Zeolite in the Zinc form.
Authors: Loayza Lenin , Guaya Diana
Published: October 2020

This work evaluated the ability of a modified zeolite to adsorb phosphates in aqueous solution. The zeolite used for this study was a modified faujasite impregnated with zinc chloride (Z-Zn) on its surface. The experiments were carried out in different stages. Adsorption was performed at different pH of the solution and the zeolitized material was found to be favorable for phosphate adsorption. The adsorption kinetics occurred after 240 minutes and reach the equilbrium, determining chemisorption reactions with a fit of the particular diffusion model (Dp) and pseudo second order, the Langmuir model was best adjusted through the isotherms. The adsorption and desorption process occurs best in the presence of HCl, the formation of residual phosphorous in the fractionation stage evidenced that the highest percentage was bound to metals such as Fe and Al.
Population turnover facilitates cultural selection for efficiency
Authors: Chimento Michael , Alarcon-Nieto Gustavo , Aplin Lucy
Published: October 2020

Selection for more efficient socially learned behaviors over alternatives is crucial for cumulative cultural evolution, yet our understanding of such cultural selection in animals is limited. We performed a cultural diffusion experiment using 18 populations of wild-caught great tits (Parus major) to ask whether more efficient innovations are subsequently selected for, and whether this process is affected by turnover. We show that gradual replacement of individuals greatly increases the probability that a more efficient behavior will invade a population's cultural repertoire, out-competing an established inefficient behavior. Turnover does not increase innovation rates, but instead increases adoption rates, as immigrants are more susceptible to novel, efficient behaviors. An agent based model further supported our results by demonstrating that this effect holds across populations of different types of learners. Altogether, these results provide strong evidence for cultural selection for efficiency in animals, and highlight the importance of population turnover for this process.
Hepatocyte Ploidy in Cats with and Without Hepatocellular Carcinoma
Authors: Johnston Andrea N. , Post Jacqueline , Langohr Ingeborg M. , Webster Cynthia R.L. , Mottram Peter , Liu Chin-Chi
Published: October 2020

BackgroundDomestic cats rarely develop hepatocellular carcinoma. The reason for the low prevalence is unknown. Reductions in hepatocellular ploidy have been associated with hepatic carcinogenesis. Recent work in mice has shown that livers with more polyploid hepatocytes are protected against the development of hepatocellular carcinoma. Hepatocyte ploidy in the domestic cat has not been evaluated. We hypothesized that ploidy would be reduced in peri-tumoral and neoplastic hepatocytes compared to normal feline hepatocytes. Using integrated fluorescence microscopy, we quantified the spectra of ploidy in hepatocellular carcinoma and healthy control tissue from paraffin embedded tissue sections. Results Feline hepatocytes are predominantly mononuclear and the number of nuclei per hepatocyte did not differ significantly between groups. Normal cats have a greater number of tetraploid hepatocytes than cats with hepatocellular carcinoma.ConclusionsTotal hepatocellular polyploidy in normal cat liver is consistent with values reported in humans, yet cellular ploidy (nuclei per cell) is greater in humans than in cats. Tetraploid cat hepatocytes are predominantly mononuclear.
Improving Access to Medicines for Non-Communicable Diseases in Rural Primary Care: Results from a Cluster Randomised Trial in a District in South India
Authors: Pati Manoj Kumar , Bhojani Upendra , Elias Maya Annie , Srini Prashanth Nuggehalli
Published: October 2020

BackgroundA large proportion of non-communicable diseases (NCD) are treatable within primary health care (PHC) settings in a cost-effective manner; however, dependence on PHCs for NCD care is comparatively low in India. The Access to Medicines (ATM) study examined the effect of a community-level and health service level package of interventions on improving availability of generic medicines at PHCs and decreasing expenditure on medicines.Method A baseline-endline quantitative experimental approach was used to assess effectiveness of the intervention (18 months) implemented across all 39 rural PHCs of three sub-districts of Tumkur district in southern Karnataka, India. Intervention consisted of three arms with A & B consisting of package of interventions aimed at health service delivery optimization within PHC, and strengthening community platforms respectively; C was the control arm. A cluster randomised household survey was used to understand health seeking behaviour, access and out-of-pocket expenditure (OOP) on key anti-diabetic and anti-hypertension medicines; similarly, facility surveys across these PHCs were conducted to assess availability of medicines. Primary outcomes of the study are mean number of days of availability of medicines, mean number of patients obtained medicines from PHC, OOP expenses and mean number of days for which medicines were procured.Result Below 50% of patients only sought care from PHCs in intervention arms and around 30% who visited got patient health records. Mean number of days of key NCD medicines availability at home did not show statistically significant differences across study arms. There was overall increase in mean days of availability of key NCD medicines at PHCs across all study arms. Although there was an overall decrease in OOP on NCD medicines and increase in number of patents visiting PHC for NCD medicines between intervention arms and control from baseline to endline the difference was not statistically significant. ConclusionThe intervention effects were not uniform within the study groups. Depending on local context some PHCs were able to overcome health system barriers better than the others. Health service interventions at PHC and community level could be hindered by wider health system challenges beyond control of localized study interventions.Trial RegistrationTrial registration number CTRI/2015/03/005640. Retrospectively Enrolled
An Energy-Efficient Human Activity Recognition System Based on Smartphones
Authors: Shi Junhao , Zuo Decheng , Zhang Zhan , Pan Daohua
Published: October 2020

Smartphone-based human activity recognition has become a considerable research field as a subdomains of pattern recognition and pervasive computing. With the increasing popularity of smartphones, HAR has prominent applications in number of fields such as health care, education, entertainment and etc. Smart devices have a huge advantage in convenience as the main acquisition and processing equipment, but the battery life of smartphone and other resources are limited for long-duration tasks. In this paper, we propose a lightweight HAR system. The system realizes HAR algorithm with deep learning algorithm. Beyond that, we introduce a clustering-center based pre-classification strategy to reduce the call frequency of the DL model. Meanwhile, we add a sampling frequency control mechanism to the inertial sensor. The goal of the whole system is to achieve low power consumption and time delay. According to the final experiment results, the energy consumption reduces about 49% and time delay reduces about 55% while the overall recognition accuracy only suffers about 10% reduction.
A New Perspective on Calmodulin Regulated Calcium and Ros Homeostasis Upon Carbon Black Nanoparticle Exposure
Authors: verma Nisha , Pink Mario , Schmitz-Spanke Simone
Published: October 2020

BackgroundToxicological studies propose that exposure to carbon black nanoparticles induces organ injuries and inflammatory responses. Besides, current understanding of the molecular mechanisms implies that carbon black nanoparticles (CBNP) exposure induces the production of reactive oxygen species (ROS) causing inflammation, mitochondrial dysfunction, or disturbance in calcium homeostasis. However, the precise mechanisms whereby CBNP exert these effects in the lung are still not fully understood. To gain insight into the possible mechanism of CBNP exerted toxicity, human alveolar epithelial cells (A549) were exposed to different concentrations of CBNP and for different time points. The reaction of the cells was monitored by the systematic use of cell-based measurements of calcium and ROS, in the presence and absence of calcium (Ca2+) pump inhibitors/chelators and antioxidants. Followed by an in-depth PCR analysis of eighty-four oxidative stress related genes.ResultsThe measurements revealed, as compared to the control, that exposure to CBNP nanoparticles leads to the generation of high ROS levels as well as a disturbance in calcium homeostasis, which remained primarily unchanged even after 24 h of exposure. Nevertheless, in presence of antioxidants N-acetylcysteine (NAC) and Trolox, ROS formation was considerably reduced without affecting the intracellular calcium concentration. On the other hand, Ca2+ pump inhibitors/chelators, BAPTA (1,2-bis(o-amino phenoxy)ethane-N, N, N′, N′-tetraacetic acid) and verapamil not only decreased the Ca2+ overload but also further decreased the ROS formation, indicating its role in CBNP induced oxidative stress. Further, a PCR array analysis of A549 cells in presence and absence of the calmodulin (CaM) antagonist W7, indicated towards nine altered oxidative stress-related genes which further confirmed our cytotoxicity results. The results suggested that CBNP exposure elevates calcium ion concentration, which further contributes to oxidative stress, via the calcium-binding protein CaM. Its inhibition with W7 leads to downregulation in gene expression of nine oxidative stress-related genes, which otherwise, as compared to control, show increased gene expression.ConclusionsThe results of the study thus confirm that exposure of lung epithelial cells to CBNP leads to oxidative stress, however, the oxidative stress itself is a result of a disturbance in both calcium and ROS homeostasis and should be considered while searching for a new strategy for prevention of CBNP - induced lung toxicity.
Risk Factors of Metabolic Bone Disease in Bronchopulmonary Dysplasia Premature Infants With Gestational Age Less Than 32 Weeks
Authors: Chen Wenwen , Zhang Zhenghai , Dai Shuzhen , Liping Xu
Published: October 2020

BackgroundMetabolic bone disease (MBD) is a complication of multifactorial aetiology in preterm infants. Several risk factors have been identified in general. Bronchopulmonary Dysplasia (BPD) infants present an increased incidence of MBD, but it is unknown which factors contribute to this. The aim of this study was to determine the risk factors for developing MBD in BPD infants.MethodsA retrospective review of the medical records of BPD infants admitted to the Neonatal Intensive Care Unit (NICU) at Zhangzhou Hospital between Jun 2016 and May 2020. BPD infants with MBD were identified, two contemporaneous without MBD matched by gestational age and gender were randomly selected as control infants for each case of MBD. The association between putative risk factors and MBD was estimated with ORs and 95% CIs. A P-value threshold ≤0.2 was used in univariate analysis for inclusion into a multivariate (adjusted) model with a P-value of < 0.05 as statistically significant.ResultsA total of 156 BPD infants were enrolled with 52 cases of MBD and 104 controls. Fetal growth restriction (OR 5.60, 95% CI, 1.77–17.72), extremely low birth weight (OR 3.70, 95% CI, 1.35–10.10), feeding volume ＜80 mL/kg/day at the end of the 4th week after birth (OR 12.21, 95% CI, 3.89–38.33), cholestasis (OR 4.29, 95% CI, 1.65–11.15), and late onset sepsis (OR 3.79, 95% CI, 1.12–12.77) were found to be statistically significant risk factors for MBD in BPD infants.ConclusionIn gestational age homogeneous BPD infants, fetal growth restriction, extremely low birth weight, feeding volume＜80 mL/kg/day at the end of the 4th week after birth and late onset sepsis are significant risk factors for MBD. These findings provide potential predictive factors for MBD in BPD infants but still warrant prospective validation.
Glutathione S-transferase M1 and T1 Genes Deletion Polymorphisms and Blood Pressure Control Among Treated Essential Hypertensive Patients in Burkina Faso.
Authors: SOMBIE Herman Karim , Tchélougou Daméhan , Sorgho Pegdwendé Abel , Kologo Jonas Koudougou , OUATTARA Abdoul Karim , Yaméogo Sakinata , Zongo Arsène Wendpagnangdé , Kiendrébéogo Isabelle Touwendpoulimdé , Yelemkouré Edwige , Adoko Enagnon Tiémoko Herman Donald , Yonli Albert Théophane , Djigma Florencia Wendkuuni , Zabsonré Patrice , Millogo Hassanata , Simporé Jacques
Published: October 2020

ObjectiveGlutathione S-transferases have been associated with experimental resistance to some drugs. The present study investigated the factors associated with blood pressure control in patients with essential hypertension, especially the role of GSTT1 and GSTM1 genes polymorphisms. This cross-sectional study in Burkina Faso consisted of 200 patients with essential hypertension and under treatment. ResultsThis cross-sectional study population consisted of 57.5 % (115/200) of patients with their hypertension under control. No statistically significant difference (p > 0.05) was found between controlled and uncontrolled (SBP and/or DBP) groups for anthropometric and biochemical parameters as well as for GSTT1 or GSTM1 gene polymorphisms. However, current alcohol consumption (OR = 3.04; CI = 1.88 - 6.13; p < 0.001), physical inactivity (OR = 3.07; CI = 1.71 - 5.49; p < 0.001), severity of hypertension (Grade III [OR = 3.79; CI = 2.00 - 7.17; p < 0.001]) and heart damage (OR = 3, 14; CI = 1.59 - 6.02; p < 0.001) were statistically more frequent in uncontrolled essential hypertension group than controlled group.
Single Institutional Outcomes of Whole Brain Radiotherapy for Metastatic Melanoma Brain Metastases
Authors: Jiang Cecilia , Kleber Troy J , Switchenko Jeffrey M , Khan Mohammad K.
Published: October 2020

Background: The management of melanoma with brain metastases (MBM) is increasingly complex, especially given recent improvements in targeted agents, immunotherapy, and radiotherapy. Whole brain radiation therapy (WBRT) is a longstanding radiotherapy technique for which reported patient outcomes and experiences are limited. We sought to report our institutional outcomes for MBM patients receiving WBRT and assess whether other clinical factors impact prognosis. Methods: A retrospective review of a single institution database was performed. Patients diagnosed with MBM from 2000-2018 treated with WBRT, with or without other systemic treatments, were included. Post-WBRT brain MRI scans were assessed at timed intervals for radiographic response. Clinical and treatment variables associated with overall survival (OS), distant failure-free survival (DFFS), local failure-free survival (LFFS), and progression-free survival (PFS) were assessed. Data on radiation-induced side effects, including radionecrosis, hemorrhage, and memory deficits, was also captured. Results: 63 patients with MBM were ultimately included in our study. 69% of patients had 5 or more brain metastases at the time of WBRT, and 68% had extracranial disease. The median dose of WBRT was 30 Gray over 10 fractions. Median follow-up was 4.0 months. Patients receiving WBRT had a median OS of 7.0 months, median PFS of 2.2 months, median DFFS of 6.1 months, and median LFFS of 4.9 months. Performance status correlated with OS on both univariate and multivariable analysis. BRAF inhibitor was the only systemic therapy to significantly impact OS on univariate analysis (HR 0.24, 95% CI 0.07-0.79, p=0.019), and this effect extended to multivariable analysis as well. Post-WBRT intralesional hemorrhage decreased DFFS on both univariate and multivariable analysis. Of patients with post-treatment brain scans available, there was a 16% rate of radionecrosis, 32% rate of hemorrhage, and 19% rate of memory deficits.Conclusions: Outcomes for MBM patients receiving WBRT indicate that WBRT remains an effective treatment strategy to control intracranial disease. Treatment-related toxicities such as intralesional hemorrhage, necrosis, or neurocognitive side effects are limited. With continued innovations in WBRT technique and systemic therapy development, MBM outcomes may continue to improve. Further trials should evaluate the role of WBRT in the modern context.
A Comparison of a Short Versus Long Postal Questionnaire on Childbirth-related Incontinence: a Randomised Controlled Trial to Evaluate Response Rates. 
Authors: Webb Sara S , Jones E , Bishop J , MacArthur C
Published: October 2020

BackgroundA future cluster randomised controlled trial (cRCT) to test an intervention to prevent postpartum urinary incontinence will use a postal questionnaire from women to obtain outcomes. This is part of a programme of work that has the overall aim of reducing the proportion of women with urinary incontinence after birth. One part of the programme was a methodology trial to compare a longer questionnaire, which includes all outcomes, with a shorter questionnaire, which includes only the most important outcomes, in order to maximise women’s response to these sensitive questions. MethodsA multicentre, stratified by community midwife team, with balanced randomisation [1:1] controlled, parallel group trial was undertaken including women under the care of 15 community midwife teams in three West Midlands NHS trusts who had given birth 10-12 weeks previously. Women under 16 years and women without a live baby on hospital discharge were excluded. Eligible women under the care of each midwife team were individually randomised in a 1:1 ratio to receive either a long or short questionnaire. Both questionnaires included questions on urinary and bowel incontinence and about advice and information on pelvic floor muscle exercise (PFME) and their PFME practice. The long questionnaire included additional questions about women’s confidence in undertaking pelvic floor muscle exercise (PFME) and their general health. For women randomised to the short questionnaire, the additional questions were only sent to women who returned the first questionnaire. The primary outcome of this trial was the response rate for completion of the urinary incontinence (UI) questions. Secondary outcomes were urinary incontinence (using ICIQ-UI SF), bowel incontinence (using RFIS), women’s performance of PFME and their confidence in this (using PFMSES) and their general health (using SF12).Results777 women were sent a questionnaire and 241 (31%) returned a completed questionnaire. There was no difference in the completion rate of the UI questions according to questionnaire length: 30.5% (119/387) of the women in the long questionnaire arm answered the UI questions compared with 31.5% (123/390) of those in the short questionnaire arm. ConclusionsThis study has used high quality trial methods and shown that response rates to the postpartum UI questions were comparable from either a longer or shorter questionnaire. Trial RegistrationISRCTN Registry: ISRCTN99859966. Date registered: 10/09/2018: http://www.isrctn.com/ISRCTN99859966
N-acetyl Cysteine Induces Quiescent-like Pancreatic Stellate Cells From an Active State and Attenuates Cancer-stroma Interactions
Authors: Feng Haimin , Moriyama Taiki , Ohuchida Kenoki , Sheng Nan , Iwamoto Chika , Shindo Koji , Shirahane Kengo , Ikenaga Naoki , Nagai Shuntaro , Nakata Kohei , Mizumoto Kazuhiro , Nakamura Masafumi
Published: October 2020

Background: Pancreatic stellate cells (PSCs) occupy the majority of the pancreatic cancer microenvironment, contributing to an aggressive behavior of pancreatic cancer cells (PCCs). Recently, anti-fibrotic agents have proven to be an effective strategy against cancer, but clinical trials have shown little efficacy and the driving mechanism remains unknown. N-acetyl-cysteine (NAC) is often used for cystic fibrosis. Pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, was often used for type II diabetes, but recently reported to inhibit metastasis of PCCs. However, few studies have focused on the effects of these two agents on cancer-stromal interactions. Method: We evaluated the expression of α-smooth muscle actin (α-SMA) and the number of lipid droplets in PSCs cultured with or without NAC. We also evaluated changes in invasiveness and proliferation in PSCs and PCCs after NAC treatment. Using an indirect coculture system, we investigated changes in proliferation, invasiveness, and migration of PSCs and PCCs. Combined treatment effects of NAC and pioglitazone were evaluated in PSCs and PCCs. In vivo, PCCs and PSCs were subcutaneously injected into mice to evaluate tumor growth. We co-transplanted KPC-derived organoids and PSCs using a splenic xenografted mouse model and evaluated the effect of combination of NAC and pioglitazone.Results: In vitro, NAC inhibited the proliferation, invasiveness, and migration of PSCs at a low concentration, but not those of PCCs. NAC treatment significantly reduced expression of α-SMA, collagen type I and fibronectin in PSCs. NAC-treated PSCs apparently present quiescent-like state with a high number of lipid droplets. Co-cultured PSCs and PCCs mutually promoted the proliferation, invasiveness, and migration of each other. However, these promotion effects were attenuated by NAC treatment. Pioglitazone maintained the NAC-induced quiescent-like state of PSCs, which were reactivated by PCC-supernatant, and enhanced chemosensitivity of PCCs. In vivo, administration of NAC to mice with subcutaneously implanted PCCs and PSCs significantly reduced tumor growth with less stromal components. The combination of NAC and pioglitazone suppressed liver metastasis in the 3D-organoid xenografted mouse model Conclusion: NAC suppressed activated PSCs and attenuates cancer-stromal interactions. NAC induces quiescent-like PSCs that were maintained in this state by pioglitazone treatment.
Generating Phone-quality Records to Train Machine Learning Models for Smartphone-based Earthquake Early Warning
Authors: Zheng Zengwei , Shi Lifei , Zhao Sha , Hou Jianmin , Sun Lin , Dong Lin , Fang Yi , Liu Jie , Li Shijian , Pan Gang
Published: October 2020

Earthquake Early Warning (EEW) system detects earthquakes and sends an early warning to areas likely to be affected, which plays a significant role in reducing earthquake damage. In recent years, as with the widespread distribution of smartphones, as well as their powerful computing ability and advanced built-in sensors, a new interdisciplinary research method of smartphone-based earthquake early warning has emerged. Smartphones-based earthquake early warning system applies signal processing techniques and machine learning algorithms to the sensor data recorded by smartphones for better monitoring earthquakes. But it is challenging to collect abundant phone-recorded seismic data for training related machine learning models and selecting appropriate features for these models. One alternative way to solve this problem is to transform the data recorded by seismic networks into phone-quality data. In this paper, we propose such a transformation method by learning the differences between the data recorded by seismic networks and smartphones, in two scenarios: phone fixed and free located on tables, respectively. By doing this, we can easily generate abundant phone-quality earthquake data to train machine learning models used in EEW systems. We evaluate our transformation method by conducting various experiments, and our method performs much better than existing methods. Furthermore, we set up a case study where we use the transformed records to train machine learning models for earthquake intensity prediction. The results show that the model trained by using our transformed data produces superior performance, suggesting that our transformation method is useful for smartphone-based earthquake early warning.
Basalt derived from highly refractory mantle sources during early Izu-Bonin-Mariana arc development
Authors: Li He , Arculus Richard , Ishizuka Osamu , Hickey-Vargas Rosemary , Yogodzinski Gene , McCarthy Anders , Kusano Yuki , Brandl Philipp , Savov Ivan , III Frank Tepley , Sun Wei-Dong
Published: October 2020

The character of magmatism associated with the early stages of subduction zone and island arc development is unlike that of mature systems, being dominated in the Izu-Bonon-Mariana (IBM) case by low-Ti-K tholeiitic basalts and boninites. Basalts recovered by coring the basement of the Amami Sankaku Basin (ASB), located west of the oldest remnant arc of the IBM system (Kyushu-Palau Ridge; KPR), were erupted at ~49 Ma, about 3 million years after subduction inception. The chain of stratovolcanoes defined by the KPR is superimposed on this basement. The basalts were sourced from upper mantle similar to that tapped following subduction inception, and represented by forearc basalt (FAB) dated at ~52-51 Ma. The mantle sources of the ASB basalt basement were more depleted by prior melt extraction than those involved in the vast majority of mid-ocean ridge (MOR) basalt generation. The ASB basalts are low-Ti-K, aluminous spinel-olivine-plagioclase-clinopyroxene-bearing tholeiites. We show this primary mineralogy is collectively distinct compared to basalts of MOR, backarc basins of the Philippine Sea Plate, forearc, or mature island arcs. In combination with bulk compositional (major and trace element abundances plus radiogenic isotope characteristics) data for the ASB basalts, we infer the upper mantle involved was hot (~1400oC), reduced, and refractory peridotite. For a few million years following subduction initiation, a broad region of mantle upwelling accompanied by partial melting prevailed. The ASB basalts were transferred rapidly from moderate pressures (1-2 GPa), preserving a mineralogy established at sub-crustal conditions, and experienced little of recharge-mix-tap-fractionate regimes typical of MOR or mature arcs.
Platelet-to-lymphocyte ratio at 24h after thrombolysis is a prognostic marker in acute ischemic stroke patients
Authors: Sun Yingying , Wang Meiqi , Wang Yan , Yan Xiuli , Jin Hang , Sun Xin , Zhang Peng , Zhu Hongjing , Yang Yi , Guo Zhen-Ni
Published: October 2020

Introduction: The role of Platelet-to-lymphocyte ratio (PLR) in outcomes of acute ischemic stroke, especially before and after intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA), has not been elucidated. Thus, the aim of this study was to evaluate the effect of PLR before and after rtPA on clinical outcomes.Methods: A total of 582 consecutive patients who had acute ischemic stroke diagnosed and received intravenous thrombolysis with rtPA were included in this study. We collected demographics, vascular risk factors, previous history of drugs and other clinical information for all patients. Specifically, blood samples for PLR values were collected on admission and at 24 hours after stroke. Multivariate logistic regression analysis was used to assess the association between PLR with the risk of poor outcome (mRS≥3), death and hemorrhagic transformation (HT). Results: Of 582 patients, 191 (32.8%) had a poor outcome, 40 (6.9%) died and 82 (14.1%) had HT. After adjustment for potential confounders, multivariate logistic regression analysis showed that higher PLR at 24h after rtPA was independently associated with an increased risk of poor outcome (OR=1.004; 95% CI:1.001-1.007; P=0.009) and the occurrence of death (OR=1.009; 95% CI:1.004-1.013; P<0.001), but not associated with the risk of HT (OR=1.003; 95% CI:0.999-1.007; P=0.165). In addition, PLR on admission was not associated with the risk of poor outcome, death and HT (all P>0.05).Conclusions: We found that PLR at 24h after rtPA can predict the risk of poor outcome and death in acute ischemic stroke patients, but PLR on admission cannot.
Fractionation and characterization of lignin from sugarcane bagasse using a sulfuric acid catalyzed solvothermal process
Authors: Imman Saksit , Khongchamnan Punjarat , Wanmolee Wanwitoo , Laosiripojana Navadol , Kreetachat Torpong , Suriyachai Nopparat
Published: October 2020

Background: Conversion of lignocellulosic residue to bioenergy and biofuel is a promising platform for global sustainability. Fractionation is an initial step for isolating lignocellulosic components for subsequent valorization. The aim of this research is to develop the solvothermal fractionation of sugarcane bagasse to produce high purity lignin. Physio-chemical structure of isolated lignin from this process was determined.Results: In this study, a central composite design-based response surface methodology (RSM) was used to optimize an acid promoter for isolating lignin from sugarcane bagasse using a solvothermal fractionation process. The reaction was carried out with sulfuric acid, in the concentration of 0.01-0.02 M and a reaction temperature of 180-200°C for 30-90 min. The optimal conditions for the experiment were obtained at the acid concentration of 0.02 M with a temperature of 180ºC for 90 min in methyl isobutyl ketone (MIBK)/methanol/water (35%:25%:40% v/v%). The results showed that 87.1% of lignin recovery was conducted in the organic phase, while 88.0% of lignin removal was done in the solid phase. Furthermore, the change in the physico-chemical characteristics of solid residue and lignin recovery was recorded using various techniques. A GPC analysis of recovered lignin from the organic fraction showed a low average Mw/Mn (1374/785 g/mol) and lower polydispersity index (1.75) compared to commercial organosolv lignin. The maximum lignin degradation temperatures of recovered lignin and commercial organosolv lignin were estimated to be 310°C and 334°C, which can point to potential relationships with the degradation of β-O-4 cross-links. The results indicated that recovered lignin is mostly cross-linked by the β-O-4 cross-links.Conclusions: The development of sulfuric acid catalyzed solvothermal process in this study provides the efficient extraction of high-value organosolv lignin from sugarcane bagasse and the production of recovered lignin in organic phase with low contamination from other contents. The lignin characteristic data can contribute to the development of lignin valorization in value-added applications.