bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sublethal effects of emamectin benzoate on life table parameters of the cotton leafworm, Spodoptera littoralis (Boisd.)
Authors: Mokbel El-Sayed , Huesien Amal 
Published: September 2020

Abstract
Background
The cotton leafworm, Spodoptera littoralis (Boisd.), is a serious economic pest in Egypt. Pest control depends mainly on chemical control with several pesticides include conventional and modern insecticides. Comprehensive analysis of pesticides impacts needs to investigate sublethal effects in addition to lethal effect.

Results
In the current study, the leaf-dip bioassay method was used to evaluate emamectin benzoate (EMB) sublethal concentrations. Results showed that EMB proved high toxicity against S. littorals with LC50 value of 0.019 mg liter−1. Life table analysis showed that treatments with LC5 and LC15 prolonged larval period, mean longevity of males and females, mean generation time (T), doubling time (DT), adult preovipositional period (APOP), and total preovipositional period (TPOP) compared with control. On the contrary, net reproduction rates (R0), intrinsic rates of increase (r), finite rate (λ), fecundity, gross reproductive rate (GRR), and relative fitness were decreased compared to control.

Conclusions
The current study clarified that sublethal concentrations of EMB induce adverse effects and suppress the population growth of S. littorals. Our results would be useful to assess the overall effects of EMB on S. littorals and can contribute effectively in pest management.
The performance of Cu2+ as dissolved cathodic electron-shuttle mediator for Cr6+ reduction in the microbial fuel cell
Authors: Gangadharan Praveena , Nambi Indumathi M. 
Published: September 2020

AbstractThe study investigates the performance of Cu2+ as dissolved cathodic electron-shuttle mediator (dcESM) for simultaneous Cr6+ reduction and electricity generation in a microbial fuel cell (MFC) at pH 2 and 4 conditions. The dcESM behavior of Cu2+ on carbon cloth (CC) catalyzes the reduction of Cr6+ into Cr3+ at pH 2 by undergoing redox reactions. However, at pH 4, a simultaneous reduction of Cu2+ and Cr6+ was observed. Cyclic voltammetry studies were performed at pH 2 and 4 to probe the dcESM behavior of Cu2+ for Cr6+ reduction on CC electrode. Also, at pH 2, increasing the concentration of Cu2+ from 50 to 500 mg L− 1 favors the Cr6+ reduction by reducing the reaction time from 108 to 48 h and improving the current production from 3.9 to 6.2 mA m− 2, respectively. Nevertheless, at pH 4, the efficacy of Cr6+ reduction and electricity generation from MFC is decreased from 63 to 18% and 4.4 to 1.1 mA m− 2, respectively, by increasing the Cu2+ concentration from 50 to 500 mg L− 1. Furthermore, the performance of dcESM behavior of Cu2+ was explored on carbon felt (CF) and platinum (Pt) electrodes, and compare the results with CC. In MFC, at pH 2, with an initial concentration of 100 mg L− 1, the reduction of Cr6+ in 60 h is 9.6 mg L− 1 for CC, 0.2 mg L− 1 for CF, and 51.3 mg L− 1 for Pt cathodes. The reduction of Cr6+ (initial concentration of 100 mg L− 1) at pH 4 in 120 h is 44.7 mg L− 1 for CC, 32.1 mg L− 1 for CF, and 70.9 mg L− 1 for Pt cathodes. Maximum power densities of 1659, 1509, and 1284 mW m− 2 were achieved when CF, CC, and Pt, respectively were employed as cathodes in the MFC.
Internal biliary diversion to avoid liver transplantation in an adult with intractable pruritus due to idiopathic intrahepatic cholestasis
Authors: Siriwardana R. C. , Jayatunge D. S. P. , Ekanayake C. S. , Tilakaratne S. , Niriella M. A. , Gunathilake B. , Dassanayake A. S. 
Published: September 2020

Abstract
Background
Cholestasis is due to the obstruction at any level of the excretory pathway of bile. One particularly troublesome symptom of cholestasis is pruritus which leads to a profound effect on a patient’s quality of life. In children with progressive familial intrahepatic cholestasis (PFIC), medical treatment often fails. An alternative surgical procedure using biliary diversion offers significant relief for intractable pruritus in non-responders.

Case presentation
A 43-year-old male presented with a history of persistent jaundice and intractable pruritus for a 2-month duration. His liver enzymes were markedly elevated. However, his liver synthetic function was preserved. After extensive evaluation, a cause for cholestasis was not identified. A multi-disciplinary decision was to consider liver transplantation, but as his liver synthetic functions were remarkably preserved and the intractable pruritus was the sole indication for a transplantation, it was finally decided that internal biliary diversion should be done for symptomatic relief. His pruritus dramatically improved at 6 weeks post-operative. His liver enzymes and bilirubin levels also decreased compared to his pre-operative status. Currently, his liver functions are being closely monitored.

Conclusion
Though it is not used in adults, the experience of biliary diversion in children with PFIC shows that there is a considerable improvement of symptoms and postpone the need for a transplant. In our patient, liver function and bilirubin as expected did not show a major improvement. But the dramatic improvement of the symptoms gave us the time to postpone the liver transplantation. A biliary diversion is a reasonable option that needs to be considered even in adults with refectory pruritus due to cholestasis.
An investigation on the behavior and morphology of sulphanilamide crystallization in different nucleation conditions
Authors: Dasari Smita Shivraj , Tallapaka Ajit Kumar , Thati Jyothi 
Published: September 2020

Abstract
Background
Crystallization is used as a purification process in majority of the industries such as pharmaceuticals, food products, chemicals, catalysts, and cosmetics. Crystallization of active pharmaceutical ingredients is carried out to increase the dissolution rate and attain sufficient bioavailability in pharmaceutical industries. It can also enhance the flow properties and drug dosage control of the active pharmaceutical ingredients.
Single crystals give us a lucid understanding of the intrinsic properties of a material. A material made up of many crystals will have grain boundaries which do not allow us to measure properties such as thermal and electrical resistance effectively. Single crystals will not have defects or impurities in them. Thus, help us in making comparisons with other materials and contribute to a better understanding of particular behaviors. Therefore, it is important to investigate the growth of single crystals.
Sulphanilamide is a sulpha class drug used as an intermediate and starting material for the production of various drugs. It is an antibacterial agent and is often used in pharmaceutics and cosmetics. In this study, we wanted to obtain sulphanilamide crystals by two different crystallization methods and compare the results gathered. Sulphanilamide usually crystallizes in the form of needles, thus is ideal for the purpose of this study. In this work, crystallization of sulphanilamide was carried out by cooling method and solvent evaporation method. In Cooling method as temperature was brought down the crystals separated out. On the other hand, in solvent evaporation method, the solvent evaporated leaving behind the crystals. The process parameters that varied included stirring rate of the solution at a constant temperature, concentration of the solute in a constant volume of solvent, solvent systems chosen-acetone, methanol and ethanol, and time allowed for crystallization.

Results
Crystals were obtained under the varying conditions. Characterization of the crystals formed was carried out using X-ray diffraction method, scanning electron microscopy, and differential scanning calorimetry. The size and morphology of the crystals formed was observed and the results were compared. It was found that the crystals obtained from using methanol as solvent, with high concentration of solute, gave the most uniform and large-sized cubic crystals under solvent evaporation method. The surface of the crystal was also seen to be smooth with well-defined edges as shown in the SEM images. Stirring reduced the size of crystals formed, and longer time of crystal formation resulted in larger crystals. Solvent evaporation method gave more uniform crystals compared to cooling method.

Conclusion
This study gives us an understanding of how each parameter affects crystal growth. Thus, optimum conditions for crystal growth can be determined.
Development of a novel TLR8 agonist for cancer immunotherapy
Authors: Wang Yuxun , Yang Heping , Li Huanping , Zhao Shuda , Zeng Yikun , Zhang Panpan , Lin Xiaoqin , Sun Xiaoxiang , Wang Longsheng , Fu Guangliang , Gao Yaqiao , Wang Pei , Gao Daxin 
Published: September 2020

AbstractToll-like receptors (TLRs) are a family of proteins that recognize pathogen associated molecular patterns (PAMPs). Their primary function is to activate innate immune responses while also involved in facilitating adaptive immune responses. Different TLRs exert distinct functions by activating varied immune cascades. Several TLRs are being pursued as cancer drug targets. We discovered a novel, highly potent and selective small molecule TLR8 agonist DN052. DN052 exhibited strong in vitro cellular activity with EC50 at 6.7 nM and was highly selective for TLR8 over other TLRs including TLR4, 7 and 9. DN052 displayed excellent in vitro ADMET and in vivo PK profiles. DN052 potently inhibited tumor growth as a single agent. Moreover, combination of DN052 with the immune checkpoint inhibitor, selected targeted therapeutics or chemotherapeutic drugs further enhanced efficacy of single agents. Mechanistically, treatment with DN052 resulted in strong induction of pro-inflammatory cytokines in ex vivo human PBMC assay and in vivo monkey study. GLP toxicity studies in rats and monkeys demonstrated favorable safety profile. This led to the advancement of DN052 into phase 1 clinical trials.
Between-Batch Bioequivalence (BBE): a Statistical Test to Evaluate In Vitro Bioequivalence Considering the Between-Batch Variability
Authors: Bodin Jonathan , Liandrat Stéphanie , Kocevar Gabriel , Petitcolas Céline 
Published: September 2020

AbstractBioequivalence testing is an essential step during the development of generic drugs. Regulatory agencies have drafted recommendations and guidelines to frame this step but without finding any consensus. Different methodologies are applied depending on the geographical region. For instance, in the EU, EMA recommends using average bioequivalence test (ABE), while in the USA, FDA recommends using population bioequivalence (PBE) test. Both methods present some limitations (e.g., when batch variability is non-negligible) making it difficult to conclude to equivalence without subsequently increasing the sample size. This article proposes an alternative method to evaluate bioequivalence: between-batch bioequivalence (BBE). It is based on the comparison between the mean difference (Reference − Test) and the Reference between-batch variability. After presenting the theoretical concepts, BBE relevance is evaluated through simulation and real case (nasal spray) studies. Simulation results showed high performance of the method based on false positive and false negative rate estimations (type I and type II errors respectively). Especially, BBE has shown significantly greater true positive rates than ABE and PBE when the Reference residual standard deviation is higher than 15%, depending on the between-batch variability and the number of batches. Finally, real case applications revealed that BBE is more efficient than ABE and PBE to demonstrate equivalence, in some well-known situations where the between-batch variability is not negligible. These results suggest that BBE could be considered as an alternative to the state-of-the-art methods allowing costless development.
Plasma Epinephrine Contributes to the Development of Experimental Hypoglycemia-Associated Autonomic Failure
Authors: Lontchi-Yimagou Eric , Aleksic Sandra , Hulkower Raphael , Gospin Rebekah , Goyal Akankasha , Kuo Bryan , Mitchell William G , You Jee Young , Upadhyay Laxmi , Carey Michelle , Sandu Oana A , Gabriely Ilan , Shamoon Harry , Hawkins Meredith 
Published: September 2020

Abstract

Background
Recurrent hypoglycemia blunts counter-regulatory responses to subsequent hypoglycemic episodes, a syndrome known as hypoglycemia-associated autonomic failure (HAAF). Since adrenergic receptor blockade has been reported to prevent HAAF, we investigated whether the hypoglycemia-associated rise in plasma epinephrine contributes to pathophysiology and reported interindividual differences in susceptibility to HAAF.

Methods
To assess the role of hypoglycemia-associated epinephrine responses in the susceptibility to HAAF, 24 adult nondiabetic subjects underwent two 2-hour hyperinsulinemic hypoglycemic clamp studies (nadir 54 mg/dL; 0-2 hours and 4-6 hours) on Day 1, followed by a third identical clamp on Day 2. We challenged an additional 7 subjects with two 2-hour infusions of epinephrine (0.03 μg/kg/min; 0-2 hours and 4-6 hours) vs saline on Day 1 followed by a 200-minute stepped hypoglycemic clamp (90, 80, 70, and 60 mg/dL) on Day 2.

Results
Thirteen out of 24 subjects developed HAAF, defined by ≥20% reduction in average epinephrine levels during the final 30 minutes of the third compared with the first hypoglycemic episode (P &lt; 0.001). Average epinephrine levels during the final 30 minutes of the first hypoglycemic episode were 2.3 times higher in subjects who developed HAAF compared with those who did not (P = 0.006).
Compared to saline, epinephrine infusion on Day 1 reduced the epinephrine responses by 27% at the 70 and 60 mg/dL glucose steps combined (P = 0.04), with a parallel reduction in hypoglycemic symptoms (P = 0.03) on Day 2.

Conclusions
Increases in plasma epinephrine reproduce key features of HAAF in nondiabetic subjects. Marked interindividual variability in epinephrine responses to hypoglycemia may explain an individual’s susceptibility to developing HAAF.
Brain Aromatase and the Regulation of Sexual Activity in Male Mice
Authors: Brooks David C , Coon V John S , Ercan Cihangir M , Xu Xia , Dong Hongxin , Levine Jon E , Bulun Serdar E , Zhao Hong 
Published: September 2020

AbstractThe biologically active estrogen estradiol has important roles in adult brain physiology and sexual behavior. A single gene, Cyp19a1, encodes aromatase, the enzyme that catalyzes the conversion of testosterone to estradiol in the testis and brain of male mice. Estradiol formation was shown to regulate sexual activity in various species, but the relative contributions to sexual behavior of estrogen that arises in the brain versus from the gonads remained unclear. To determine the role of brain aromatase in regulating male sexual activity, we generated a brain-specific aromatase knockout (bArKO) mouse. A newly generated whole-body total aromatase knockout mouse of the same genetic background served as a positive control. Here we demonstrate that local aromatase expression and estrogen production in the brain is partially required for male sexual behavior and sex hormone homeostasis. Male bArKO mice exhibited decreased sexual activity in the presence of strikingly elevated circulating testosterone. In castrated adult bArKO mice, administration of testosterone only partially restored sexual behavior; full sexual behavior, however, was achieved only when both estradiol and testosterone were administered together. Thus, aromatase in the brain is, in part, necessary for testosterone-dependent male sexual activity. We also found that brain aromatase is required for negative feedback regulation of circulating testosterone of testicular origin. Our findings suggest testosterone activates male sexual behavior in part via conversion to estradiol in the brain. These studies provide foundational evidence that sexual behavior may be modified through inhibition or enhancement of brain aromatase enzyme activity and/or utilization of selective estrogen receptor modulators.
Novel Mutations and Genes That Impact on Growth in Short Stature of Undefined Aetiology: The EPIGROW Study
Authors: Perchard Reena , Murray Philip George , Payton Antony , Highton Georgina Lee , Whatmore Andrew , Clayton Peter Ellis 
Published: September 2020

AbstractBackgroundChildren with short stature of undefined aetiology (SS-UA) may have undiagnosed genetic conditions.PurposeTo identify mutations causing short stature (SS) and genes related to SS, using candidate gene sequence data from the European EPIGROW study.MethodsFirst, we selected exonic single nucleotide polymorphisms (SNPs), in cases and not controls, with minor allele frequency (MAF) &lt; 2%, whose carriage fitted the mode of inheritance. Known mutations were identified using Ensembl and gene-specific databases. Variants were classified as pathogenic, likely pathogenic, or variant of uncertain significance using criteria from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. If predicted by ≥ 5/10 algorithms (eg, Polyphen2) to be deleterious, this was considered supporting evidence of pathogenicity. Second, gene-based burden testing determined the difference in SNP frequencies between cases and controls across all and then rare SNPs. For genotype/phenotype relationships, we used PLINK, based on haplotype, MAF &gt; 2%, genotype present in &gt; 75%, and Hardy Weinberg equilibrium P &gt; 10–4.ResultsFirst, a diagnostic yield of 10% (27/263) was generated by 2 pathogenic (nonsense in ACAN) and a further 25 likely pathogenic mutations, including previously known missense mutations in FANCB, IGFIR, MMP13, NPR2, OBSL1, and PTPN11. Second, genes related to SS: all methods identified PEX2. Another 7 genes (BUB1B, FANCM, CUL7, FANCA, PTCH1, TEAD3, BCAS3) were identified by both gene-based approaches and 6 (A2M, EFEMP1, PRKCH, SOS2, RNF135, ZBTB38) were identified by gene-based testing for all SNPs and PLINK.ConclusionsSuch panels improve diagnosis in SS-UA, extending known disease phenotypes. Fourteen genes related to SS included some known to cause growth disorders as well as novel targets.
Eligibility for Liver Transplantation in Patients with Perihilar Cholangiocarcinoma
Authors: Vugts Jaynee J. A. , Gaspersz Marcia P. , Roos Eva , Franken Lotte C. , Olthof Pim B. , Coelen Robert J. S. , van Vugt Jeroen L. A. , Labeur Tim A. , Brouwer Lieke , Besselink Marc G. H. , IJzermans Jan N. M. , Darwish Murad Sarwa , van Gulik Thomas M. , de Jonge Jeroen , Polak Wojciech G. , Busch Olivier R. C. , Erdmann Joris L. , Groot Koerkamp Bas , Buettner Stefan 
Published: September 2020

AbstractBackgroundLiver transplantation (LT) has been performed in a select group of patients presenting with unresectable or primary sclerosing cholangitis (PSC)-associated perihilar cholangiocarcinoma (pCCA) in the Mayo Clinic with a reported 5-year overall survival (OS) of 53% on intention-to-treat analysis. The objective of this study was to estimate eligibility for LT in a cohort of pCCA patients in two tertiary referral centers.MethodsPatients diagnosed with pCCA between 2002 and 2014 were included from two tertiary referral centers in the Netherlands. The selection criteria used by the Mayo Clinic were retrospectively applied to determine the proportion of patients that would have been eligible for LT.ResultsA total of 732 consecutive patients with pCCA were identified, of whom 24 (4%) had PSC-associated pCCA. Overall, 154 patients had resectable disease on imaging and 335 patients were ineligible for LT because of lymph node or distant metastases. An age limit of 70 years led to the exclusion of 50 patients who would otherwise be eligible for LT. After applying the Mayo Clinic criteria, only 34 patients (5%) were potentially eligible for LT. Median survival from diagnosis for these 34 patients was 13 months (95% CI 3–23).ConclusionOnly 5% of all patients presenting with pCCA were potentially eligible for LT under the Mayo criteria. Without transplantation, a median OS of about 1 year was observed.
Using contact data to model the impact of contact tracing and physical distancing to control the SARS-CoV-2 outbreak in Kenya
Authors: Wagner Moritz , Kombe Ivy K. , Kiti Moses Chapa , Aziza Rabia , Barasa Edwine , Nokes D. James 
Published: September 2020

Background: Across the African continent, other than South Africa, COVID-19 cases have remained relatively low. Nevertheless, in Kenya, despite early implementation of containment measures and restrictions, cases have consistently been increasing. Contact tracing forms one of the key strategies in Kenya, but may become infeasible as the caseload grows. Here we explore different contact tracing strategies by distinguishing between household and non-household contacts and how these may be combined with other non-pharmaceutical interventions. Methods: We extend a previously developed branching process model for contact tracing to include realistic contact data from Kenya. Using the contact data, we generate a synthetic population of individuals and their contacts categorised by age and household membership. We simulate the initial spread of SARS-CoV-2 through this population and look at the effectiveness of a number of non-pharmaceutical interventions with a particular focus on different contact tracing strategies and the potential effort involved in these. Results: General physical distancing and avoiding large group gatherings combined with contact tracing, where all contacts are isolated immediately, can be effective in slowing down the outbreak, but were, under our base assumptions, not enough to control it without implementing extreme stay at home policies. Under optimistic assumptions with a highly overdispersed R0 and a short delay from symptom onset to isolation, control was possible with less stringent physical distancing and by isolating household contacts only. Conclusions: Without strong physical distancing measures, controlling the spread of SARS-CoV-2 is difficult. With limited resources, physical distancing combined with the isolation of households of detected cases can form a moderately effective strategy, and control is possible under optimistic assumptions. More data are needed to understand transmission in Kenya, in particular by studying the settings that lead to larger transmission events, which may allow for more targeted responses, and collection of representative age-related contact data.